Alzheimer’s disease(AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and...Alzheimer’s disease(AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD.In this review, we summarize the latest achievements,including diagnostic biomarkers, polygenic hazard score,amyloid and tau PET imaging, clinical trials targeting amyloid-beta(Ab), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.展开更多
Morinda officinalis oligosaccharides(MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. H...Morinda officinalis oligosaccharides(MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan(5-HTP) → serotonin(5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan;meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation,and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood-brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide,as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.展开更多
Background：This study aimed to evaluate the effects of standard rescue procedure （SRP） in improving severe trauma treatments in China.Methods：This study was conducted in 12 hospitals located in geographically and ...Background：This study aimed to evaluate the effects of standard rescue procedure （SRP） in improving severe trauma treatments in China.Methods：This study was conducted in 12 hospitals located in geographically and industrially different cities in China.A standard procedure on severe trauma rescue was established as a general rule for staff training and patient treatment.A regional network （system） efficiently integrating prehospital rescue,emergency room treatments,and hospital specialist treatments was built under the rule for information sharing and improving severe trauma treatments.Treatment outcomes were compared between before and I year after the implementation of the SRP.Results：The outcomes of a total of 74,615 and 12,051 trauma cases were collected from 12 hospitals before and after the implementation of the SRP.Implementation of the SRP led to efficient cooperation and information sharing of different treatment services.The emergency response time,prehospital transit time,emergency rescue time,consultation call time,and mortality rate of patients were 24.24 ± 4.32 min,45.69 ± 3.89 min,6.38 ± 1.05 min,17.53 ± 0.72 min,and 33.82% ± 3.87% （n =441）,respectively,before the implementation of the standardization and significantly reduced to 10.11 ± 3.21 min,22.39 ± 4.32 min,3.26 ± 0.89 min,3.45 ± 0.45 min,and 20.49% ± 3.11%,separately （n =495,P 〈 0.05） after that.Conclusions：Staff training and SRP can significantly improve the efficiency of severe trauma treatments in China.展开更多
Esophageal squamous cell carcinoma(ESCC)is a common malignant tumor of the digestive system worldwide,especially in China.Due to the lack of effective early detection methods,ESCC patients often present at an advanced...Esophageal squamous cell carcinoma(ESCC)is a common malignant tumor of the digestive system worldwide,especially in China.Due to the lack of effective early detection methods,ESCC patients often present at an advanced stage at the time of diagnosis,which seriously affects the prognosis of patients.At present,early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy.Therefore,there is an unmet need for a noninvasive method to detect ESCC in the early stages.With the emergence of a large class of non-invasive diagnostic tools,serum tumor markers have attracted much attention because of their potential for detection of early tumors.Therefore,the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC.This article reviews the recent advances in the discovery of blood-based ESCC biomarkers,and discusses the origins,clinical applications,and technical challenges of clinical validation of various types of biomarkers.展开更多
Peripheral nerve injury is a common clinical problem and affects the quality of life of patients. Traditional restoration methods are not satisfactory. Researchers increasingly focus on the field of tissue engineering...Peripheral nerve injury is a common clinical problem and affects the quality of life of patients. Traditional restoration methods are not satisfactory. Researchers increasingly focus on the field of tissue engineering. The three key points in establishing a tissue engineering material are the biological scaffold material, the seed cells and various growth factors. Understanding the type of nerve injury, the construction of scaffold and the process of repair are necessary to solve peripheral nerve injury and promote its regeneration. This review describes the categories of peripheral nerve injury, fundamental research of peripheral nervous tissue engineering and clinical research on peripheral nerve scaffold material, and paves a way for related research and the use of conduits in clinical practice.展开更多
Background Resistin, a newly discovered cysteine-rich hormone secreted mainly by adipose tissues, has been proposed to form a biochemical link between obesity and type 2 diabetes. However, the resistin receptor has no...Background Resistin, a newly discovered cysteine-rich hormone secreted mainly by adipose tissues, has been proposed to form a biochemical link between obesity and type 2 diabetes. However, the resistin receptor has not yet been identified. This study aimed to identify resistin binding proteins/receptor. Methods Three cDNA fragments with the same 11 bp 5＇ sequence were found by screening a cDNA phage display library of rat multiple tissues. As the reading frames of the same 11 bp 5＇ sequence were interrupted by a TGA stop codon, plaque lift assay was consequently used to prove the readthrough phenomenon. The stop codon in the same 11 bp 5＇ sequence was replaced by tryptophan, and the binding activity of the coded peptide [AWIL, which was designated as resistin binding peptide （RBP）] with resistin was identified by the confocal microscopy technique and the affinity chromatography experiment, pDual GC-resistin and pDual GC-resistin binding peptide were co-transfected into 3T3-L1 cells to confirm the function of resistin binding peptide. Results Three cDNA fragments with the same 11 bp 5＇ sequence were found. The TGA stop codon in reading frames of the same 11 bp 5＇ sequence was proved to be readthroughed. The binding activity of RBP with resistin was consequently identified. The expression of the resistin binding peptide in 3T3-L1 preadipocytes expressing pDual G-C-resistin significantly inhibited the adipogenic differentiation. Conclusion RBP could effectively rescue the promoted differentiation of resistin overxepressed 3T3-L1 preadipocyte.展开更多
Game theory can be applied to the air combat decision-making problem of multiple unmanned combat air vehicles(UCAVs).However,it is difficult to have satisfactory decision-making results completely relying on air comba...Game theory can be applied to the air combat decision-making problem of multiple unmanned combat air vehicles(UCAVs).However,it is difficult to have satisfactory decision-making results completely relying on air combat situation information,because there is a lot of time-sensitive information in a complex air combat environment.In this paper,a constraint strategy game approach is developed to generate intelligent decision-making for multiple UCAVs in complex air combat environment with air combat situation information and time-sensitive information.Initially,a constraint strategy game is employed to model attack-defense decision-making problem in complex air combat environment.Then,an algorithm is proposed for solving the constraint strategy game based on linear programming and linear inequality(CSG-LL).Finally,an example is given to illustrate the effectiveness of the proposed approach.展开更多
Earthworm toxicity tests are useful tools for terrestrial risk assessment but require a hierarchy of test designs that differ in effect levels （behavior, sublethal, lethal）. In this study, the toxicity of chlorpyrif...Earthworm toxicity tests are useful tools for terrestrial risk assessment but require a hierarchy of test designs that differ in effect levels （behavior, sublethal, lethal）. In this study, the toxicity of chlorpyrifos contaminated soil on earthworms was assessed. In addition to the acute and chronic tests, an avoidance response test was applied. Earthworms were exposed to sublethal and lethal concentration of chlorpyrifos, and evaluated for acute toxicity, growth, fecundity and avoidance response after a certain exposure period. The test methods covered all important ecological relevant endpoints （acute, chronic, behavioral）. Concentration of 78.91 mg/kg, chlorpyrifos caused significant toxic effects in all test methods, but at lower test concentrations, only significant chronic toxic effects could be observed. In present study, chlorpyrifos had adverse effect on growth and fecundity in earthworm exposed to 5 mg/kg chlorpyrifos after eight weeks. The avoidance response test, however, showed significant repellent effects at concentration of 40 mg/kg chlorpyrifos. For chlorpyrifos, concentration affecting avoidance response was far greater than growth and fecundity, it seemed likely that earthworms were not able to escape from pesticide-contaminated soil into the clean soil in field and hence were exposed continuously to elevated concentrations of pesticides.展开更多
Background:Clinically amyopathic dermatomyositis(CADM)is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease(ILD).Poor prognosis of the patients was strongly ass...Background:Clinically amyopathic dermatomyositis(CADM)is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease(ILD).Poor prognosis of the patients was strongly associated with rapid progressive ILD.The aim of this study was to identify risk factors for prediction of different types of ILD in CADM.Methods:In this study,data of 108 inpatients with CADM were collected,including 87 with ILD.The baseline clinical data and laboratory parameters,including myositis-specific and associated antibodies and tumor-associated antigens were analyzed to identify risk factors for acute or subacute interstitial pneumonitis(A/SIP)and chronic interstitial pneumonitis(CIP).Results:In 87 patients with CADM-ILD,39(36.1%)were A/SIP,and 48(44.4%)were CIP.There were 22(20.4%)patients with asymptomatic ILD who were detected by routine high resolution computed tomography.Cytokeratin-19 fragment(CYFRA21-1)was significantly higher in CADM-ILD than that in CADM patients without ILD;carcinoembryonic antigen and neuron-specific enolase were significantly elevated in A/SIP than that in CIP.Patients with A/SIP had a higher positive rate of anti-melanoma differentiation-associated gene 5(MDA5),while patients with CIP had a higher positive rate of anti PL-12 and anti-Ro-52.Logistic regression analysis indicated that elevation of CYFRA21-1 was a risk factor for ILD,higher titer of anti-MDA5 indicated increased likelihood for A/SIP,and higher titer of anti-Ro-52 was also clearly associated with CIP.Conclusions:This study indicated that the prevalence of ILD was high in CADM.Asymptomatic ILD has been previously underestimated.Anti-MDA5 was a risk factor for the presence of A/SIP,and CYFRA21-1 was a risk factor for ILD.展开更多
BACKGROUND Peutz-Jeghers syndrome(PJS)is a clinically rare disease with pigmented spots on the lips and mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to tumors as clinical manif...BACKGROUND Peutz-Jeghers syndrome(PJS)is a clinically rare disease with pigmented spots on the lips and mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to tumors as clinical manifestations.Effective preventive and curative methods are still lacking.Here we summarize our experience with 566 Chinese patients with PJS from a Chinese medical center with regard to the clinical features,diagnosis,and treatment.AIM To explore the clinical features,diagnosis,and treatment of PJS in a Chinese medical center.METHODS The diagnosis and treatment information of 566 cases of PJS admitted to the Air Force Medical Center from January 1994 to October 2022 was summarized.A clinical database was established covering age,gender,ethnicity,family history,age at first treatment,time and sequence of appearance of mucocutaneous pigmentation,polyp distribution,quantity,and diameter,frequency of hospitalization,fre-quency of surgical operations,etc.The clinical data was retrospectively analyzed using SPSS 26.0 software,with P<0.05 considered statistically significant.RESULTS Of all the patients included,55.3%were male and 44.7%were female.Median time to the appearance of mucocutaneous pigmentation was 2 years,and median time from the appearance of mucocutaneous pigmentation to the occurrence of abdominal symptoms was 10 years.The vast majority(92.2%)of patients underwent small bowel endoscopy and treatment,with 2.3%having serious complications.There was a statistically significant difference in the number of enteroscopies between patients with and without canceration(P=0.004,Z=-2.882);71.2%of patients underwent surgical operation,75.6%of patients underwent surgical operation before the age of 35 years,and there was a statistically significant difference in the frequency of surgical operations between patients with and without cancer(P=0.000,Z=-5.127).At 40 years of age,the cumulative risk of intussusception in PJS was approximately 72.0%,and at 50 years,the cumulative risk of intussusception in PJS was展开更多
Background： Antimicrobial de-escalation refers to starting the antimicrobial treatment with broad-spectrum antibiotics, followed by narrowing the drug spectrum according to culture results. The present study evaluate...Background： Antimicrobial de-escalation refers to starting the antimicrobial treatment with broad-spectrum antibiotics, followed by narrowing the drug spectrum according to culture results. The present study evaluated the effect of de-escalation on ventilator-associated pneumonia （VAP） in trauma patients. Methods： This retrospective study was conducted on trauma patients with VAP, who received de-escalation therapy （de-escalation group） or non-de-escalation therapy （non-de-escalation group）. Propensity score matching method was used to balance the baseline characteristics between both groups. The 28-day mortality, length of hospitalization and Intensive Care Unit stay, and expense of antibiotics and hospitalization between both groups were compared. Multivariable analysis explored the factors that influenced the 28-day mortality and implementation of de-escalation. Results： Among the 156 patients, 62 patients received de-escalation therapy and 94 patients received non-de-escalation therapy. No significant difference was observed in 28-day mortality between both groups （28.6% vs. 23.8%, P = 0.620）. The duration of antibiotics treatment in the de-escalation group was shorter than that in the non-de-escalation group （11 [8-13] vs. 14 [8-19] days, P = 0.045）. The expenses of antibiotics and hospitalization in de-escalation group were significantly lower than that in the non-de-escalation group （6430 ± 2730 vs. 7618 ± 2568 RMB Yuan, P = 0.043 and 19,173 ± 16,861 vs. 24,184 ± 12,039 RMB Yuan, P = 0.024, respectively）. Multivariate analysis showed that high Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE Ⅱ） score, high injury severity score, multi-drug resistant （MDR） infection, and inappropriate initial antibiotics were associated with patients＇ 28-day mortality, while high APACHEⅡ score, MDR infection and inappropriate initial antibiotics were independent factors that prevented the implementation of de-escalation. Conclusions： De-escalation strategy in the t展开更多
Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the ther- apeutic effects of local admini...Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the ther- apeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly（lactic-co-glycolic acid） biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local ap- plication of icariin after spinal injury can promote peripheral nerve regeneration.展开更多
Background Cigarette smoking has an influence on both arterial-type and venous-type thrombosis. However, little is known about the direct effect of cigarette smoke extract （CSE） on fibrinolytic activity of human umb...Background Cigarette smoking has an influence on both arterial-type and venous-type thrombosis. However, little is known about the direct effect of cigarette smoke extract （CSE） on fibrinolytic activity of human umbilical vein endothelial cells （HUVECs）. Most recently, simvastatin has been marked in its effect on endothelial cells protection and anticoagulation. In this study, the effect of CSE on the expression of tissue-type plasminogen activator （t-PA） and plasminogen activator inhibitor-l（PAl-1） in HUVECs was addressed. The role of simvastatin in CSE-induced fibrinolytic activity changes was investigated as well. Methods The fourth to fifth generation of HUVECs were incubated respectively with 0, 5%, 10% and 20% CSE for 6 hours or exposed to 5% CSE for 0, 4, 6, 8, 12, 24 hours to determine the expression changes of t-PA and PAl-1 protein. Meanwhile, cells were also accordingly exposed either to 5% CSE alone or simvastatin pre-treated and 5% CSE for 24 hours to assess the role of simvastatin in CSE-induced t-PA and PAl-1 protein and mRNA expression in HUVECs. RT-PCR and ELISA techniques were used for detecting the t-PA or PAl-1 mRNA and protein. Results After 6-hour exposure to CSE, the expression levels of t-PA protein in 10% and 20% CSE-treated groups reduced significantly （（0.0365±0.0083） ng/ml, （0.0255±0.0087） ng/ml） when compared with that of control group （（0.0660±0.0120） ng/ml） （P 〈0.05）. In contrast, the levels of PAl-1 protein in 5%, 10% and 20% CSE-treated groups increased remarkably （（13.3225±0.5680） ng/ml, （14.2675±1.5380） ng/ml, （14.4292±1.6230） ng/ml） when compared with that of control group （（8.5193_±0.7537）ng/ml） （P〈0.05）. After stimulation with 5% CSE for 0, 4, 6, 8, 12, 24 hours, the levels of PAl-1 protein increased over time and reached the peak at 24 hours （（14.6400±1.0651） ng/ml）, which was significantly higher than that of control group （（12.0656±0.6148） ng/ml） （P 〈0.05）. Additionally, 展开更多
Based on numerical simulations,this study highlights the sedimentation and erosion problems around a sand barrier through the relationship between the shear stress of the surface around the sand barrier and the critic...Based on numerical simulations,this study highlights the sedimentation and erosion problems around a sand barrier through the relationship between the shear stress of the surface around the sand barrier and the critical shear stress of sand grains.The numerical simulation results were verified using data measured by the wind tunnel test.The results showed that when the porosity was the same,the size and position of the vortex on the leeward side of the sand barrier were related to the inlet wind speed.As the wind speed increased,the vortex volume increased and the positions of the separation and reattachment points moved toward the leeward side.When the porosity of the sand barrier was 30%,the strength of the acceleration zone above the sand barrier was the highest,and the strength of the acceleration zone was negatively correlated with the porosity.Sand erosion and sedimentation distance were related to wind speed.With an increase in wind speed,the sand grain forward erosion or reverse erosion areas on the leeward side of the sand barrier gradually replaced the sedimentation area.With an increase in porosity,the sand sedimentation distance on the leeward side of the sand barrier gradually shortened,and the sand erosion area gradually disappeared.The sand sedimentation distance on the leeward side of the sand barrier with 30%porosity was the longest.The numerical simulation results were in good agreement with the wind tunnel test results.Based on the sand erosion and sedimentation results of the numerical simulation and wind tunnel test,when the porosity was 30%,the protection effect of the High Density Polyethylene(HDPE)board sand barrier was best.展开更多
BACKGROUND:Opportunistic infection of Candida albicans(C.albicans) has become a serious problem in immunocompromised patients.The study aimed to explore the mechanism of enterogenous infection of C.albicans in immunoc...BACKGROUND:Opportunistic infection of Candida albicans(C.albicans) has become a serious problem in immunocompromised patients.The study aimed to explore the mechanism of enterogenous infection of C.albicans in immunocompromised rats under severe acute pancreatitis(SAP).METHODS:Sprague Dawley(SD) rats(n=100) were randomly assigned into 5 groups as the following:blank group,cyclophosphamide+ceftriaxone+SAP group,cyclophosphamide+ceftriaxone group,cyclophosphamide+SAP group,and cyclophosphamide group.The rats were sacrificed at 5and 10 days,and their jejunum,colon,mesenteric lymph nodes,pancreas,intestinal content,and blood were quickly collected to detect C.albicans.A region of the 25 S rRNA gene was chosen and amplified by polymerase chain reaction(PCR) to differentiate C.albicans genotypes.The amplified products were further sequenced and compared to judge their homology.RESULTS:Compared with the Cyclophosphamide group,the combination of immunosuppressants and broad-spectrum antibiotics significantly increased the colonization of C.albicans in intestine in 5 and 10 days.Pure SAP stress did not increase the opportunistic infection of C.albicans.The PCR products of C.albicans isolates all belonged to the genotype A family,and sequence alignment showed that the amplified fragments were homologous.CONCLUSION:The damage of immune system and broad-spectrum antimicrobial agents are important risk factors for opportunistic fungal infection.Intestinal tract is an important source for genotype-A C.albicans to translocate and invade into bloodstream.展开更多
Light passing through a subwavelength hole in an opaque plate is a fundamental concern in both optical science and applications.Using both simulations and experiments,we show that,when a subwavelength hole in a silver...Light passing through a subwavelength hole in an opaque plate is a fundamental concern in both optical science and applications.Using both simulations and experiments,we show that,when a subwavelength hole in a silver thin film is surrounded by well-designed patterns of grooves,the wavefront of the infrared light through it can be shaped into a preset complicated pattern such as a Latin letter‘L’or‘O’at a given position instead of being diffracted in all directions.The design is created via the surface-wave-holography method,which allows direct determination of the surface plasmonic structure for a given wavefront-engineering functionality without the need to solve complex inverse problems.The results will deepen current understanding of this enduring issue and will find applications in many fields such as wave manipulation and sensing.展开更多
Catharanthus roseus L. （Madagascar periwinkle） biosynthesizes a diverse array of secondary metabolites including anticancer dimeric alkaloids （vinblastine and vincristine） and antihypertensive alkaloids （ajmalici...Catharanthus roseus L. （Madagascar periwinkle） biosynthesizes a diverse array of secondary metabolites including anticancer dimeric alkaloids （vinblastine and vincristine） and antihypertensive alkaloids （ajmalicine and serpentine）. The multi-step terpenoid indole alkaloids （TIAs） biosynthetic pathway in C. roseus is complex and is under strict molecular regulation. Many enzymes and genes involved in the TIAs biosynthesis have been studied in recent decades. Moreover, some regulatory proteins were found recently to control the production of TIAs in C. roseus. Based on mastering the rough scheme of the pathway and cloning the related genes, metabolic engineering of TIAs biosynthesis has been studied in C. roseus aiming at increasing the desired secondary metabolites in the past few years. The present article summarizes recent advances in isolation and characterization of TIAs biosynthesis genes and transcriptional regulators involved in the second metabolic control in C. roseus. Metabolic engineering applications in TIAs pathway via overexpression of these genes and regulators in C. roseus are also discussed.展开更多
Although stress has been known to increase the susceptibility of pathogen infection,the underlying mechanism remains elusive.In this study,we reported that restraint stress dramatically enhanced the morbidity and mort...Although stress has been known to increase the susceptibility of pathogen infection,the underlying mechanism remains elusive.In this study,we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus(H1N1)and obviously aggravated lung inflammation.Corticosterone(CORT),a main type of glucocorticoids in rodents,was secreted in the plasma of stressed mice.We further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling(MAVS)protein-transduced IFN-βproduction without affecting its mRNA level,while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in mice.Mechanistically,the effect of CORT was mediated by proteasome-dependent degradation of MAVS,thereby resulting in the impediment of MAVS-transduced IFN-βgeneration in vivo and in vitro.Furthermore,RNA-seq assay results indicated the involvement of Mitofusin 2(Mfn2)in this process.Gain-and loss-offunction experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of MAVS.Co-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2(HR1),MAVS(C-terminal/TM)and SYVN1(TM).Collectively,our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a‘fine tuning’of antiviral innate immunity in response to influenza infection under stress.展开更多
Background Study of the relationship between mast cells and atherosclerosis is mostly dependent on pathological observation and cytology experiments. To investigate the effects of mast cells degranulation on plaque an...Background Study of the relationship between mast cells and atherosclerosis is mostly dependent on pathological observation and cytology experiments. To investigate the effects of mast cells degranulation on plaque and their possible mechanisms we used apolipoprotein E knockout mice which had been placed perivascular common carotid collar with mast cells degranulator compound 48-80. Methods Forty apolipoprotein E knockout mice were fed a western-type diet and operated on with placement of perivascular right common carotid collar. Four weeks after surgery, the mice were intraperitoneally injected with compound 48-80 （0.5 mg/kg） or D-Hanks every other day for 4 times. The serum lipids and activity of tryptase were measured. Tissue sections were stained with hematoxylin and eosin. Corresponding sections were stained with toluidine blue and immunohistochemically with antibodies against macrophage-specific antigen, a-smooth muscle actin, interleukin-1β and von Willebrand factor. Simultaneously, basic fibroblast growth factor was detected by in situ hybridization and immunofluorescence. Results No pathological change was observed in common carotid non-collar placement but atherogenesis in common carotid collar placement of both groups. There was a significant increase in plaque area （（5.85±0.75）×10^4 vs （0.86±0.28）×10^4 um^2, P 〈0.05）, the degree of lumen stenosis （（81±15）% vs （41±12）%, P 〈0.05）, the activity of tryptase in serum （（0.57±0.13） U/L vs （0.36±0.10） U/L, P 〈0.05）, and the percentage of degranulated mast cells （（80.6±17.8）% vs （13.5±4.1）%, P 〈0.05）. The expressions of macrophage-specific antigen, α-smooth muscle actin, interleukin-1β, basic fibroblast growth factor and the density of neovessel in plaque were more in the compound 48-80 group than in the control group. Conclusions Perivascular common carotid collar placement can promote atherosclerotic plaque formation in apolipoprotein E knockout mice. Compound 48-80 increases plaque are展开更多
The clinical effects of 2-mm small gap sleeve bridging of the biological conduit to repair periph- eral nerve injury are better than in the traditional epineurium suture, so it is possible to replace the epineurium su...The clinical effects of 2-mm small gap sleeve bridging of the biological conduit to repair periph- eral nerve injury are better than in the traditional epineurium suture, so it is possible to replace the epineurium suture in the treatment of peripheral nerve injury. This study sought to identify the regeneration law of nerve fibers in the biological conduit. A nerve regeneration chamber was constructed in models of sciatic nerve injury using 2-mm small gap sleeve bridging of a biodegradable biological conduit. The results showed that the biological conduit had good his- tocompatibility. Tissue and cell apoptosis in the conduit apparently lessened, and regenerating nerve fibers were common. The degeneration regeneration law of Schwann cells and axons in the conduit was quite different from that in traditional epineurium suture. During the prime period for nerve fiber regeneration （2-8 weeks）, the number of Schwann cells and nerve fibers was higher in both proximal and distal ends, and the effects of the small gap sleeve bridging method were better than those of the traditional epineurium suture. The above results provide an objec- tive and reliable theoretical basis for the clinical application of the biological conduit small gap sleeve bridging method to repair peripheral nerve injury.展开更多
基金supported by the the Chinese Ministry of Science and Technology (2016YFC1306401)
文摘Alzheimer’s disease(AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD.In this review, we summarize the latest achievements,including diagnostic biomarkers, polygenic hazard score,amyloid and tau PET imaging, clinical trials targeting amyloid-beta(Ab), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.
基金supported by Key Project of Beijing Natural Science Foundation (No.7181007,China)the CAMS Innovation Fund for Medical Sciences (CIFMS+2 种基金Nos.2016-I2M-3-011,20211-I2M-007,2021-I2M-1-027,and 2021-I2M-1-028,China)National Natural Science Foundation of China (Nos.81973290 and 82173888)Beijing Key Laboratory of Non-Clinical Drug Metabolism and PK/PD study (Z141102004414062,China)。
文摘Morinda officinalis oligosaccharides(MOO) are an oral drug approved in China for the treatment of depression in China. However, MOO is hardly absorbed so that their anti-depressant mechanism has not been elucidated. Here, we show that oral MOO acted on tryptophan → 5-hydroxytryptophan(5-HTP) → serotonin(5-HT) metabolic pathway in the gut microbiota. MOO could increase tryptophan hydroxylase levels in the gut microbiota which accelerated 5-HTP production from tryptophan;meanwhile, MOO inhibited 5-hydroxytryptophan decarboxylase activity, thus reduced 5-HT generation,and accumulated 5-HTP. The raised 5-HTP from the gut microbiota was absorbed to the blood, and then passed across the blood-brain barrier to improve 5-HT levels in the brain. Additionally, pentasaccharide,as one of the main components in MOO, exerted the significant anti-depressant effect through a mechanism identical to that of MOO. This study reveals for the first time that MOO can alleviate depression via increasing 5-HTP in the gut microbiota.
文摘Background：This study aimed to evaluate the effects of standard rescue procedure （SRP） in improving severe trauma treatments in China.Methods：This study was conducted in 12 hospitals located in geographically and industrially different cities in China.A standard procedure on severe trauma rescue was established as a general rule for staff training and patient treatment.A regional network （system） efficiently integrating prehospital rescue,emergency room treatments,and hospital specialist treatments was built under the rule for information sharing and improving severe trauma treatments.Treatment outcomes were compared between before and I year after the implementation of the SRP.Results：The outcomes of a total of 74,615 and 12,051 trauma cases were collected from 12 hospitals before and after the implementation of the SRP.Implementation of the SRP led to efficient cooperation and information sharing of different treatment services.The emergency response time,prehospital transit time,emergency rescue time,consultation call time,and mortality rate of patients were 24.24 ± 4.32 min,45.69 ± 3.89 min,6.38 ± 1.05 min,17.53 ± 0.72 min,and 33.82% ± 3.87% （n =441）,respectively,before the implementation of the standardization and significantly reduced to 10.11 ± 3.21 min,22.39 ± 4.32 min,3.26 ± 0.89 min,3.45 ± 0.45 min,and 20.49% ± 3.11%,separately （n =495,P 〈 0.05） after that.Conclusions：Staff training and SRP can significantly improve the efficiency of severe trauma treatments in China.
基金National Natural Science Foundation of China,No.31600632 and No.81972801Natural Science Foundation of Guangdong Province,No.2018A030307079 and No.2019A1515011873+1 种基金Innovative and Strong School Project of Guangdong,No.2018KTSCX068Key Disciplinary Project of Clinical Medicine under the Guangdong High-level University Development Program.
文摘Esophageal squamous cell carcinoma(ESCC)is a common malignant tumor of the digestive system worldwide,especially in China.Due to the lack of effective early detection methods,ESCC patients often present at an advanced stage at the time of diagnosis,which seriously affects the prognosis of patients.At present,early detection of ESCC mainly depends on invasive and expensive endoscopy and histopathological biopsy.Therefore,there is an unmet need for a noninvasive method to detect ESCC in the early stages.With the emergence of a large class of non-invasive diagnostic tools,serum tumor markers have attracted much attention because of their potential for detection of early tumors.Therefore,the identification of serum tumor markers for early detection of ESCC is undoubtedly one of the most effective ways to achieve early diagnosis and treatment of ESCC.This article reviews the recent advances in the discovery of blood-based ESCC biomarkers,and discusses the origins,clinical applications,and technical challenges of clinical validation of various types of biomarkers.
基金supported by the National Natural Science Foundation of China,No.31040043,31671248(to NH),No.81171146,81372044,30971526(to BGJ)the Chinese National Ministry of Science and Technology(973 Project),No.2014CB542201(to PXZ)+4 种基金the Ministry of Education Innovation Team,China,No.IRT1201(to PXZ)the Fostering Young Scholars of Peking University Health Science Center,China,No.BMU2017PY013(to PXZ)the Chinese National General Program of National Natural Science Fund,China(to PXZ)the Beijing City Science&Technology New Star Cross Project,China,No.2018019(to PXZ)the National Natural Science Foundation of China,No.31771322,31571235,51373023,21171019,31640045,31571236,31471144,31100860,31371210(to PXZ)
文摘Peripheral nerve injury is a common clinical problem and affects the quality of life of patients. Traditional restoration methods are not satisfactory. Researchers increasingly focus on the field of tissue engineering. The three key points in establishing a tissue engineering material are the biological scaffold material, the seed cells and various growth factors. Understanding the type of nerve injury, the construction of scaffold and the process of repair are necessary to solve peripheral nerve injury and promote its regeneration. This review describes the categories of peripheral nerve injury, fundamental research of peripheral nervous tissue engineering and clinical research on peripheral nerve scaffold material, and paves a way for related research and the use of conduits in clinical practice.
基金This study was supported by grants from the National Natural Science Foundation of China (No. 30371502) the Natural Science Foundation of Jiangsu Province (No. BK2001120)Jiangsu Provincial Health Bureau (No. RC2002061).
文摘Background Resistin, a newly discovered cysteine-rich hormone secreted mainly by adipose tissues, has been proposed to form a biochemical link between obesity and type 2 diabetes. However, the resistin receptor has not yet been identified. This study aimed to identify resistin binding proteins/receptor. Methods Three cDNA fragments with the same 11 bp 5＇ sequence were found by screening a cDNA phage display library of rat multiple tissues. As the reading frames of the same 11 bp 5＇ sequence were interrupted by a TGA stop codon, plaque lift assay was consequently used to prove the readthrough phenomenon. The stop codon in the same 11 bp 5＇ sequence was replaced by tryptophan, and the binding activity of the coded peptide [AWIL, which was designated as resistin binding peptide （RBP）] with resistin was identified by the confocal microscopy technique and the affinity chromatography experiment, pDual GC-resistin and pDual GC-resistin binding peptide were co-transfected into 3T3-L1 cells to confirm the function of resistin binding peptide. Results Three cDNA fragments with the same 11 bp 5＇ sequence were found. The TGA stop codon in reading frames of the same 11 bp 5＇ sequence was proved to be readthroughed. The binding activity of RBP with resistin was consequently identified. The expression of the resistin binding peptide in 3T3-L1 preadipocytes expressing pDual G-C-resistin significantly inhibited the adipogenic differentiation. Conclusion RBP could effectively rescue the promoted differentiation of resistin overxepressed 3T3-L1 preadipocyte.
基金supported by Major Projects for Science and Technology Innovation 2030(Grant No.2018AA0100800)Equipment Pre-research Foundation of Laboratory(Grant No.61425040104)in part by Jiangsu Province“333”project under Grant BRA2019051.
文摘Game theory can be applied to the air combat decision-making problem of multiple unmanned combat air vehicles(UCAVs).However,it is difficult to have satisfactory decision-making results completely relying on air combat situation information,because there is a lot of time-sensitive information in a complex air combat environment.In this paper,a constraint strategy game approach is developed to generate intelligent decision-making for multiple UCAVs in complex air combat environment with air combat situation information and time-sensitive information.Initially,a constraint strategy game is employed to model attack-defense decision-making problem in complex air combat environment.Then,an algorithm is proposed for solving the constraint strategy game based on linear programming and linear inequality(CSG-LL).Finally,an example is given to illustrate the effectiveness of the proposed approach.
基金Preject supported by the New Century Excellent Talents in Chinese Uni-versity (No. NCET-04-0914)the National Natural Science Foundationof China (No. 30640022)Yunnan Natural Sciences Foundations (No.2002C0001Z, 2005C0004Q).
文摘Earthworm toxicity tests are useful tools for terrestrial risk assessment but require a hierarchy of test designs that differ in effect levels （behavior, sublethal, lethal）. In this study, the toxicity of chlorpyrifos contaminated soil on earthworms was assessed. In addition to the acute and chronic tests, an avoidance response test was applied. Earthworms were exposed to sublethal and lethal concentration of chlorpyrifos, and evaluated for acute toxicity, growth, fecundity and avoidance response after a certain exposure period. The test methods covered all important ecological relevant endpoints （acute, chronic, behavioral）. Concentration of 78.91 mg/kg, chlorpyrifos caused significant toxic effects in all test methods, but at lower test concentrations, only significant chronic toxic effects could be observed. In present study, chlorpyrifos had adverse effect on growth and fecundity in earthworm exposed to 5 mg/kg chlorpyrifos after eight weeks. The avoidance response test, however, showed significant repellent effects at concentration of 40 mg/kg chlorpyrifos. For chlorpyrifos, concentration affecting avoidance response was far greater than growth and fecundity, it seemed likely that earthworms were not able to escape from pesticide-contaminated soil into the clean soil in field and hence were exposed continuously to elevated concentrations of pesticides.
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.81801615 and 81871289).
文摘Background:Clinically amyopathic dermatomyositis(CADM)is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease(ILD).Poor prognosis of the patients was strongly associated with rapid progressive ILD.The aim of this study was to identify risk factors for prediction of different types of ILD in CADM.Methods:In this study,data of 108 inpatients with CADM were collected,including 87 with ILD.The baseline clinical data and laboratory parameters,including myositis-specific and associated antibodies and tumor-associated antigens were analyzed to identify risk factors for acute or subacute interstitial pneumonitis(A/SIP)and chronic interstitial pneumonitis(CIP).Results:In 87 patients with CADM-ILD,39(36.1%)were A/SIP,and 48(44.4%)were CIP.There were 22(20.4%)patients with asymptomatic ILD who were detected by routine high resolution computed tomography.Cytokeratin-19 fragment(CYFRA21-1)was significantly higher in CADM-ILD than that in CADM patients without ILD;carcinoembryonic antigen and neuron-specific enolase were significantly elevated in A/SIP than that in CIP.Patients with A/SIP had a higher positive rate of anti-melanoma differentiation-associated gene 5(MDA5),while patients with CIP had a higher positive rate of anti PL-12 and anti-Ro-52.Logistic regression analysis indicated that elevation of CYFRA21-1 was a risk factor for ILD,higher titer of anti-MDA5 indicated increased likelihood for A/SIP,and higher titer of anti-Ro-52 was also clearly associated with CIP.Conclusions:This study indicated that the prevalence of ILD was high in CADM.Asymptomatic ILD has been previously underestimated.Anti-MDA5 was a risk factor for the presence of A/SIP,and CYFRA21-1 was a risk factor for ILD.
基金Supported by Beijing Capital Medical Development Research Fund,No.Shoufa2020-2-5122Outstanding Young Talents Program of Air Force Medical Center,PLA,No.22BJQN004Clinical Program of Air Force Medical University,No.Xiaoke2022-07.
文摘BACKGROUND Peutz-Jeghers syndrome(PJS)is a clinically rare disease with pigmented spots on the lips and mucous membranes and extremities,scattered gastrointestinal polyps,and susceptibility to tumors as clinical manifestations.Effective preventive and curative methods are still lacking.Here we summarize our experience with 566 Chinese patients with PJS from a Chinese medical center with regard to the clinical features,diagnosis,and treatment.AIM To explore the clinical features,diagnosis,and treatment of PJS in a Chinese medical center.METHODS The diagnosis and treatment information of 566 cases of PJS admitted to the Air Force Medical Center from January 1994 to October 2022 was summarized.A clinical database was established covering age,gender,ethnicity,family history,age at first treatment,time and sequence of appearance of mucocutaneous pigmentation,polyp distribution,quantity,and diameter,frequency of hospitalization,fre-quency of surgical operations,etc.The clinical data was retrospectively analyzed using SPSS 26.0 software,with P<0.05 considered statistically significant.RESULTS Of all the patients included,55.3%were male and 44.7%were female.Median time to the appearance of mucocutaneous pigmentation was 2 years,and median time from the appearance of mucocutaneous pigmentation to the occurrence of abdominal symptoms was 10 years.The vast majority(92.2%)of patients underwent small bowel endoscopy and treatment,with 2.3%having serious complications.There was a statistically significant difference in the number of enteroscopies between patients with and without canceration(P=0.004,Z=-2.882);71.2%of patients underwent surgical operation,75.6%of patients underwent surgical operation before the age of 35 years,and there was a statistically significant difference in the frequency of surgical operations between patients with and without cancer(P=0.000,Z=-5.127).At 40 years of age,the cumulative risk of intussusception in PJS was approximately 72.0%,and at 50 years,the cumulative risk of intussusception in PJS was
文摘Background： Antimicrobial de-escalation refers to starting the antimicrobial treatment with broad-spectrum antibiotics, followed by narrowing the drug spectrum according to culture results. The present study evaluated the effect of de-escalation on ventilator-associated pneumonia （VAP） in trauma patients. Methods： This retrospective study was conducted on trauma patients with VAP, who received de-escalation therapy （de-escalation group） or non-de-escalation therapy （non-de-escalation group）. Propensity score matching method was used to balance the baseline characteristics between both groups. The 28-day mortality, length of hospitalization and Intensive Care Unit stay, and expense of antibiotics and hospitalization between both groups were compared. Multivariable analysis explored the factors that influenced the 28-day mortality and implementation of de-escalation. Results： Among the 156 patients, 62 patients received de-escalation therapy and 94 patients received non-de-escalation therapy. No significant difference was observed in 28-day mortality between both groups （28.6% vs. 23.8%, P = 0.620）. The duration of antibiotics treatment in the de-escalation group was shorter than that in the non-de-escalation group （11 [8-13] vs. 14 [8-19] days, P = 0.045）. The expenses of antibiotics and hospitalization in de-escalation group were significantly lower than that in the non-de-escalation group （6430 ± 2730 vs. 7618 ± 2568 RMB Yuan, P = 0.043 and 19,173 ± 16,861 vs. 24,184 ± 12,039 RMB Yuan, P = 0.024, respectively）. Multivariate analysis showed that high Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE Ⅱ） score, high injury severity score, multi-drug resistant （MDR） infection, and inappropriate initial antibiotics were associated with patients＇ 28-day mortality, while high APACHEⅡ score, MDR infection and inappropriate initial antibiotics were independent factors that prevented the implementation of de-escalation. Conclusions： De-escalation strategy in the t
基金supported by grants from the National Program on Key Basic Research Project of China(973 Program),No.2014CB542200the National Natural Science Foundation of China,No.31271284,81171146,31100860+1 种基金the Natural Science Foundation of Beijing of China,No.7142164Program for Innovative Research Team in University of Ministry of Education of China,No.IRT1201
文摘Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the ther- apeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly（lactic-co-glycolic acid） biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local ap- plication of icariin after spinal injury can promote peripheral nerve regeneration.
文摘Background Cigarette smoking has an influence on both arterial-type and venous-type thrombosis. However, little is known about the direct effect of cigarette smoke extract （CSE） on fibrinolytic activity of human umbilical vein endothelial cells （HUVECs）. Most recently, simvastatin has been marked in its effect on endothelial cells protection and anticoagulation. In this study, the effect of CSE on the expression of tissue-type plasminogen activator （t-PA） and plasminogen activator inhibitor-l（PAl-1） in HUVECs was addressed. The role of simvastatin in CSE-induced fibrinolytic activity changes was investigated as well. Methods The fourth to fifth generation of HUVECs were incubated respectively with 0, 5%, 10% and 20% CSE for 6 hours or exposed to 5% CSE for 0, 4, 6, 8, 12, 24 hours to determine the expression changes of t-PA and PAl-1 protein. Meanwhile, cells were also accordingly exposed either to 5% CSE alone or simvastatin pre-treated and 5% CSE for 24 hours to assess the role of simvastatin in CSE-induced t-PA and PAl-1 protein and mRNA expression in HUVECs. RT-PCR and ELISA techniques were used for detecting the t-PA or PAl-1 mRNA and protein. Results After 6-hour exposure to CSE, the expression levels of t-PA protein in 10% and 20% CSE-treated groups reduced significantly （（0.0365±0.0083） ng/ml, （0.0255±0.0087） ng/ml） when compared with that of control group （（0.0660±0.0120） ng/ml） （P 〈0.05）. In contrast, the levels of PAl-1 protein in 5%, 10% and 20% CSE-treated groups increased remarkably （（13.3225±0.5680） ng/ml, （14.2675±1.5380） ng/ml, （14.4292±1.6230） ng/ml） when compared with that of control group （（8.5193_±0.7537）ng/ml） （P〈0.05）. After stimulation with 5% CSE for 0, 4, 6, 8, 12, 24 hours, the levels of PAl-1 protein increased over time and reached the peak at 24 hours （（14.6400±1.0651） ng/ml）, which was significantly higher than that of control group （（12.0656±0.6148） ng/ml） （P 〈0.05）. Additionally,
基金financially supported by the fellowship of the China Postdoctoral Science Foundation(2021M703466)the Natural Science Foundation of Gansu Province,China(20JR10RA231)+1 种基金the Basic Research Innovation Group Project of Gansu Province,China(21JR7RA347)an Special Funds for Guiding Local Scientific and Technological Development by the Central Government(22ZY1QA005)。
文摘Based on numerical simulations,this study highlights the sedimentation and erosion problems around a sand barrier through the relationship between the shear stress of the surface around the sand barrier and the critical shear stress of sand grains.The numerical simulation results were verified using data measured by the wind tunnel test.The results showed that when the porosity was the same,the size and position of the vortex on the leeward side of the sand barrier were related to the inlet wind speed.As the wind speed increased,the vortex volume increased and the positions of the separation and reattachment points moved toward the leeward side.When the porosity of the sand barrier was 30%,the strength of the acceleration zone above the sand barrier was the highest,and the strength of the acceleration zone was negatively correlated with the porosity.Sand erosion and sedimentation distance were related to wind speed.With an increase in wind speed,the sand grain forward erosion or reverse erosion areas on the leeward side of the sand barrier gradually replaced the sedimentation area.With an increase in porosity,the sand sedimentation distance on the leeward side of the sand barrier gradually shortened,and the sand erosion area gradually disappeared.The sand sedimentation distance on the leeward side of the sand barrier with 30%porosity was the longest.The numerical simulation results were in good agreement with the wind tunnel test results.Based on the sand erosion and sedimentation results of the numerical simulation and wind tunnel test,when the porosity was 30%,the protection effect of the High Density Polyethylene(HDPE)board sand barrier was best.
基金supported by grants from the Research Foundation of Shanghai Minhang District Municipal Commission of Health and Family Planning(2013MW12)the Research Foundation of Shanghai Municipal Commission of Health and Family Planning(201540136)
文摘BACKGROUND:Opportunistic infection of Candida albicans(C.albicans) has become a serious problem in immunocompromised patients.The study aimed to explore the mechanism of enterogenous infection of C.albicans in immunocompromised rats under severe acute pancreatitis(SAP).METHODS:Sprague Dawley(SD) rats(n=100) were randomly assigned into 5 groups as the following:blank group,cyclophosphamide+ceftriaxone+SAP group,cyclophosphamide+ceftriaxone group,cyclophosphamide+SAP group,and cyclophosphamide group.The rats were sacrificed at 5and 10 days,and their jejunum,colon,mesenteric lymph nodes,pancreas,intestinal content,and blood were quickly collected to detect C.albicans.A region of the 25 S rRNA gene was chosen and amplified by polymerase chain reaction(PCR) to differentiate C.albicans genotypes.The amplified products were further sequenced and compared to judge their homology.RESULTS:Compared with the Cyclophosphamide group,the combination of immunosuppressants and broad-spectrum antibiotics significantly increased the colonization of C.albicans in intestine in 5 and 10 days.Pure SAP stress did not increase the opportunistic infection of C.albicans.The PCR products of C.albicans isolates all belonged to the genotype A family,and sequence alignment showed that the amplified fragments were homologous.CONCLUSION:The damage of immune system and broad-spectrum antimicrobial agents are important risk factors for opportunistic fungal infection.Intestinal tract is an important source for genotype-A C.albicans to translocate and invade into bloodstream.
基金This work was supported by the National Basic Research Foundation of China under grant no.2011CB922002 and Knowledge Innovation Program of the Chinese Academy of Sciences(No.Y1V2013L11).
文摘Light passing through a subwavelength hole in an opaque plate is a fundamental concern in both optical science and applications.Using both simulations and experiments,we show that,when a subwavelength hole in a silver thin film is surrounded by well-designed patterns of grooves,the wavefront of the infrared light through it can be shaped into a preset complicated pattern such as a Latin letter‘L’or‘O’at a given position instead of being diffracted in all directions.The design is created via the surface-wave-holography method,which allows direct determination of the surface plasmonic structure for a given wavefront-engineering functionality without the need to solve complex inverse problems.The results will deepen current understanding of this enduring issue and will find applications in many fields such as wave manipulation and sensing.
文摘Catharanthus roseus L. （Madagascar periwinkle） biosynthesizes a diverse array of secondary metabolites including anticancer dimeric alkaloids （vinblastine and vincristine） and antihypertensive alkaloids （ajmalicine and serpentine）. The multi-step terpenoid indole alkaloids （TIAs） biosynthetic pathway in C. roseus is complex and is under strict molecular regulation. Many enzymes and genes involved in the TIAs biosynthesis have been studied in recent decades. Moreover, some regulatory proteins were found recently to control the production of TIAs in C. roseus. Based on mastering the rough scheme of the pathway and cloning the related genes, metabolic engineering of TIAs biosynthesis has been studied in C. roseus aiming at increasing the desired secondary metabolites in the past few years. The present article summarizes recent advances in isolation and characterization of TIAs biosynthesis genes and transcriptional regulators involved in the second metabolic control in C. roseus. Metabolic engineering applications in TIAs pathway via overexpression of these genes and regulators in C. roseus are also discussed.
基金supported,in part,by Natural Science Foundation of China(grant numbers 81622050,81573675,U1801284,81673709,81873209)National Key Research and Development Program of China(grant number 2017YFC1700404)+4 种基金the Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(grant number 2017BT01Y036)and GDUPS(2019)the Guangdong Science and Technology Foundation for Distinguished Young Scholars(grant number 2017A030306004)the Youth Top-notch Talent Support Program of Guangdong Province(2016TQ03R586)the Program of Hong Kong Scholar(XJ2016017)the Science and Technology Program of Guangzhou(grant number 201903010062).
文摘Although stress has been known to increase the susceptibility of pathogen infection,the underlying mechanism remains elusive.In this study,we reported that restraint stress dramatically enhanced the morbidity and mortality of mice infected with the influenza virus(H1N1)and obviously aggravated lung inflammation.Corticosterone(CORT),a main type of glucocorticoids in rodents,was secreted in the plasma of stressed mice.We further found that this stress hormone significantly boosted virus replication by restricting mitochondrial antiviral signaling(MAVS)protein-transduced IFN-βproduction without affecting its mRNA level,while the deficiency of MAVS abrogated stress/CORT-induced viral susceptibility in mice.Mechanistically,the effect of CORT was mediated by proteasome-dependent degradation of MAVS,thereby resulting in the impediment of MAVS-transduced IFN-βgeneration in vivo and in vitro.Furthermore,RNA-seq assay results indicated the involvement of Mitofusin 2(Mfn2)in this process.Gain-and loss-offunction experiments indicated that Mfn2 interacted with MAVS and recruited E3 ligase SYVN1 to promote the polyubiquitination of MAVS.Co-immunoprecipitation experiments clarified an interaction between any two regions of Mfn2(HR1),MAVS(C-terminal/TM)and SYVN1(TM).Collectively,our findings define the Mfn2-SYVN1 axis as a new signaling cascade for proteasome-dependent degradation of MAVS and a‘fine tuning’of antiviral innate immunity in response to influenza infection under stress.
基金The study was supported by a grant from the National Natural Science Foundation of China （No. 30470720）.
文摘Background Study of the relationship between mast cells and atherosclerosis is mostly dependent on pathological observation and cytology experiments. To investigate the effects of mast cells degranulation on plaque and their possible mechanisms we used apolipoprotein E knockout mice which had been placed perivascular common carotid collar with mast cells degranulator compound 48-80. Methods Forty apolipoprotein E knockout mice were fed a western-type diet and operated on with placement of perivascular right common carotid collar. Four weeks after surgery, the mice were intraperitoneally injected with compound 48-80 （0.5 mg/kg） or D-Hanks every other day for 4 times. The serum lipids and activity of tryptase were measured. Tissue sections were stained with hematoxylin and eosin. Corresponding sections were stained with toluidine blue and immunohistochemically with antibodies against macrophage-specific antigen, a-smooth muscle actin, interleukin-1β and von Willebrand factor. Simultaneously, basic fibroblast growth factor was detected by in situ hybridization and immunofluorescence. Results No pathological change was observed in common carotid non-collar placement but atherogenesis in common carotid collar placement of both groups. There was a significant increase in plaque area （（5.85±0.75）×10^4 vs （0.86±0.28）×10^4 um^2, P 〈0.05）, the degree of lumen stenosis （（81±15）% vs （41±12）%, P 〈0.05）, the activity of tryptase in serum （（0.57±0.13） U/L vs （0.36±0.10） U/L, P 〈0.05）, and the percentage of degranulated mast cells （（80.6±17.8）% vs （13.5±4.1）%, P 〈0.05）. The expressions of macrophage-specific antigen, α-smooth muscle actin, interleukin-1β, basic fibroblast growth factor and the density of neovessel in plaque were more in the compound 48-80 group than in the control group. Conclusions Perivascular common carotid collar placement can promote atherosclerotic plaque formation in apolipoprotein E knockout mice. Compound 48-80 increases plaque are
基金supported by grants from the National Program on Key Basic Research Project of China(973 Program),No.2014CB542200Program for Innovative Research Team in University of Ministry of Education of China,No.IRT1201+1 种基金the National Natural Science Foundation of China,No.31271284,31171150,81171146,30971526,31100860,31040043,31371210Program for New Century Excellent Talents in University of Ministry of Education of China,No.BMU20110270
文摘The clinical effects of 2-mm small gap sleeve bridging of the biological conduit to repair periph- eral nerve injury are better than in the traditional epineurium suture, so it is possible to replace the epineurium suture in the treatment of peripheral nerve injury. This study sought to identify the regeneration law of nerve fibers in the biological conduit. A nerve regeneration chamber was constructed in models of sciatic nerve injury using 2-mm small gap sleeve bridging of a biodegradable biological conduit. The results showed that the biological conduit had good his- tocompatibility. Tissue and cell apoptosis in the conduit apparently lessened, and regenerating nerve fibers were common. The degeneration regeneration law of Schwann cells and axons in the conduit was quite different from that in traditional epineurium suture. During the prime period for nerve fiber regeneration （2-8 weeks）, the number of Schwann cells and nerve fibers was higher in both proximal and distal ends, and the effects of the small gap sleeve bridging method were better than those of the traditional epineurium suture. The above results provide an objec- tive and reliable theoretical basis for the clinical application of the biological conduit small gap sleeve bridging method to repair peripheral nerve injury.
