BACKGROUND Cirrhosis is a chronic late stage liver disease associated with hepatitis viruses,alcoholism, and metabolic disorders, such as Wilson disease(WD). There are no clear markers or clinical features that define...BACKGROUND Cirrhosis is a chronic late stage liver disease associated with hepatitis viruses,alcoholism, and metabolic disorders, such as Wilson disease(WD). There are no clear markers or clinical features that define cirrhosis originating from these disparate origins. We hypothesized that cirrhosis is not one disease and cirrhosis of different etiology may have differential clinical hepatic features.AIM To delineate the liver features between WD-associated cirrhosis and hepatitis Bassociated cirrhosis in the Chinese population.METHODS In this observational study, we reviewed the medical data of consecutive inpatients who had WD-associated cirrhosis or hepatitis B-associated cirrhosis from January 2010 to August 2018, and excluded patients who had carcinoma,severe heart or pulmonary diseases, or other liver diseases. According to the etiology of cirrhosis, patients were divided into two groups: WD-associated cirrhosis group(60 patients) and hepatitis B-associated cirrhosis group(56 patients). The liver fibrosis degree, liver function indices, and portal hypertension features of these patients were compared between the two groups.RESULTS No inter-group differences were observed in the diagnostic liver fibrosis markers,however, clinical features clearly defined the origin of cirrhosis. WD-associated cirrhosis patients(16-29 years) had lower levels of alanine transaminase,aspartate transaminase, and bilirubin, lower prothrombin time, lower incidence of hepatic encephalopathy, and lower portal vein diameter(P < 0.05), compared to cirrhosis resulting from hepatitis B in older patients(45-62 years). Importantly,they had decreased risks of progression from Child-Pugh grade A to B(odds ratio = 0.046, 95% confidence interval: 0.006-0.387, P = 0.005) and of ascites(odds ratio = 0.08, 95% confidence interval: 0.01-0.48, P = 0.005). Conversely, WDassociated cirrhosis patients had a higher risk of splenomegaly(odds ratio = 4.15,95% confidence interval: 1.38-12.45, P = 0.011).CONCLUSION WD-associated cirrhosis presents a highe展开更多
AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors(PPAR)-δ agonist treatment in nonalcoholic fatty liver disease(NAFLD) models.METHODS: Male C57BL/6J mice were ...AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors(PPAR)-δ agonist treatment in nonalcoholic fatty liver disease(NAFLD) models.METHODS: Male C57BL/6J mice were classified according to control or high fat diet(HFD) with or without PPAR-δ agonist(GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide(LPS), HFD + LPS + GW group]. Hep G2 cells were exposed to palmitic acid(PA) and/or LPS in the absence or presence of GW.RESULTS: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin(IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In Hep G2 cells, PA and LPS treatment markedly increased m RNA of several nucleotide-binding andoligomerization domain-like receptor family members(NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α.CONCLUSION: PPAR-δ agonist reduces fatty acidinduced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.展开更多
目的:探讨儿童NTRK重排间叶源性肿瘤临床和病理学特征,以提高对该类疾病的认识。方法:收集上海交通大学医学院附属上海儿童医学中心及新加坡KK Women′s and Children′s Hospital从2017年1月至2019年9月5例手术切除标本,采用EnVision...目的:探讨儿童NTRK重排间叶源性肿瘤临床和病理学特征,以提高对该类疾病的认识。方法:收集上海交通大学医学院附属上海儿童医学中心及新加坡KK Women′s and Children′s Hospital从2017年1月至2019年9月5例手术切除标本,采用EnVision法检测免疫组织化学表型,荧光原位杂交(FISH)检测相关基因并对NTRK基因重排进行克隆性分析。结果:该组5例患儿,3例男性,2例女性。年龄从3个月到13岁,部位包括软组织(膝、胸腔、腹壁)和肾,肿瘤大小为4.5~12.5 cm。组织学检查主要呈梭形细胞肿瘤,浸润性生长,可伴有炎性细胞。免疫表型上,肿瘤细胞阳性表达Pan-TRK,分子检测均存在NTRK基因重排,包括DCTN1-NTRK1的发现。除2例目前接受靶向药物治疗,其余均为无疾病进展病例,随访时间9~29个月。结论:NTRK重排间叶源性肿瘤,其肿瘤发生部位广泛,组织学图像多变。免疫组织化学Pan-TRK可以帮助诊断,NTRK基因检测确认其存在重排是诊断的金标准,对不能完整切除或有复发、转移病例建议靶向药物治疗。展开更多
One of the most common lesions present in the spermatozoa of human infertility patients is an idiopathic failure of sperm-egg recognition. Although this unique cellular interaction can now be readily by-passed by assi...One of the most common lesions present in the spermatozoa of human infertility patients is an idiopathic failure of sperm-egg recognition. Although this unique cellular interaction can now be readily by-passed by assisted reproductive strategies such as intracytoplasmic sperm injection （ICSI）, recent large-scale epidemiological studies have encouraged the cautious use of this technology and highlighted the need for further research into the mechanisms responsible for defective sperm-egg recognition. Previous work in this field has established that the sperm domains responsible for oocyte interaction are formed during spermatogenesis prior to being dynamically modified during epididymal maturation and capacitation in female reproductive tract. While the factors responsible for the regulation of these sequential maturational events are undoubtedly complex, emerging research has identified the molecular chaperone, heat shock protein A2 （HSPA2）, as a key regulator of these events in human spermatozoa. HSPA2 is a testis-enriched member of the 70 kDa heat shock protein family that promotes the folding, transport, and assembly of protein complexes and has been positively correlated with in vitro fertilization （IVF） success. Furthermore, reduced expression of HSPA2 from the human sperm proteome leads to an impaired capacity for cumulus matrix dispersal, sperm-egg recognition and fertilization following both IVF and ICSI. In this review, we consider the evidence supporting the role of HSPA2 in sperm function and explore the potential mechanisms by which it is depleted in the spermatozoa of infertile patients. Such information offers novel insights into the molecular mechanisms governing sperm function.展开更多
It is well known that the entanglement of a quantum state is invariant under local unitary transformations.This rule dictates,for example,that the entanglement of internal degrees of freedom of a photon remains invari...It is well known that the entanglement of a quantum state is invariant under local unitary transformations.This rule dictates,for example,that the entanglement of internal degrees of freedom of a photon remains invariant during free-space propagation.Here,we outline a scenario in which this paradigm does not hold.Using local Bell states engineered from classical vector vortex beams with non-separable degrees of freedom,the so-called classically entangled states,we demonstrate that the entanglement evolves during propagation,oscillating between maximally entangled(purely vector)and product states(purely scalar).We outline the spin–orbit interaction behind these novel propagation dynamics and confirm the results experimentally,demonstrating spin–orbit coupling in paraxial beams.This demonstration highlights a hitherto unnoticed property of classical entanglement and simultaneously offers a device for the on-demand delivery of vector states to targets,for example,for dynamic laser materials processing,switchable resolution within stimulated emission depletion(STED)systems,and a tractor beam for entanglement.展开更多
As AI, starting with ChatGPT has become increasingly prevalent in academic discussions, school especially, colleges have become hotspots of AI activities and debates. Colleges have the responsibility of addressing not...As AI, starting with ChatGPT has become increasingly prevalent in academic discussions, school especially, colleges have become hotspots of AI activities and debates. Colleges have the responsibility of addressing not only the academic, integrity-based concerns of students using AI for their homework, but also as the forebearers of new learning and technology, how AI will change their students’ futures and careers. In this study, we will explore the different factors, such as Computer Science Score and location, that might affect how much a college discusses AI, ChatGPT specifically. To demonstrate the validity of our research, we used self-collected data with our methods detailed below.展开更多
The environment can impose strong limitations on the efficacy of signal transmission. In particular, for vibratory communication, the signaling environment is often extremely heterogeneous at small scales. Nevertheles...The environment can impose strong limitations on the efficacy of signal transmission. In particular, for vibratory communication, the signaling environment is often extremely heterogeneous at small scales. Nevertheless, natural selection is expected to select for signals well-suited for effective transmission. Here, we test for substrate-dependent signal efficacy in the wolf spider Schizocosa stridulans Strattou 1991. We first explore the transmission characteristics of this important signaling mo- dality by playing recorded substrate-bome signals through three different substrates （leaf litter, pine litter, and red clay） and measuring the propagated signal. We found that the substrate-bome signal of S. stridulans attenuates the least on leaf litter, the substrate upon which the species is naturally found. Next, by assessing mating success with artificially muted and non-muted males across different signaling substrates （leaf litter, pine litter, and sand）, we explored the relationship between substrate-bome signaling and signaling substrate for mating success. We found that muted males were unsuccessful in obtaining copulations re- gardless of substrate, while mating success was dependent on the signaling substrate for non-muted males. For non-muted males, more males copulated on leaf litter than any other substrate. Taken together, these results confLrm the importance of sub- strate-bome signaling in S. stridulans and suggest a match between signal properties and signal efficacy - leaf litter transmits the signal most effectively and males are most successful in obtaining copulations on leaf litter [Current Zoology 56 （3）： 370-378, 2010].展开更多
AIM: To elucidate the question of whether the ocular trauma score(OTS) and the zones of injury could be used as a predictive model of traumatic and post traumatic retinal detachment(RD) in patients with open globe inj...AIM: To elucidate the question of whether the ocular trauma score(OTS) and the zones of injury could be used as a predictive model of traumatic and post traumatic retinal detachment(RD) in patients with open globe injury(OGI).METHODS: A retrospective observational chart analysis of OGI patients was performed. The collected variables consisted of age, date, gender, time of injury, time until repair, mechanism of injury, zone of injury, injury associated vitreous hemorrhage, trauma associated RD, post traumatic RD, aphakia at injury, periocular trauma and OTS in cases of OGI. RESULTS: Totally 102 patients with traumatic OGI with a minimum of 12 mo follow-up and a median age at of 48.6 y(range: 3-104 y) were identified. Final best corrected visual acuity(BCVA) was independent from the time of repair, yet a statistically significant difference was present between the final BCVA and the zone of injury. Severe trauma presenting with an OTS score Ⅰ(P<0.0001) or Ⅱ(P<0.0001) revealed a significantly worse BCVA at last follow up when compared to the cohort with an OTS score >Ⅲ. OGI associated RD was observed in 36/102 patients(35.3%), whereas post traumatic RD(defined as RD following 14 d after OGI) occurred in 37 patients(36.3%). OGI associated RD did not correlate with the OTS and the zone of injury(P=0.193), yet post traumatic RD correlated significantly with zone Ⅲ injuries(P=0.013). CONCLUSION: The study shows a significant association between lower OTS score and zone Ⅲ injury with lower final BCVA and a higher number of surgeries, but only zone Ⅲ could be significantly associated with a higher rate of RD.展开更多
AIM To assess the performance of proposed scores specific for acute-on-chronic liver failure in predicting shortterm mortality among patients with alcoholic hepatitis.METHODS We retrospectively collected data from 264...AIM To assess the performance of proposed scores specific for acute-on-chronic liver failure in predicting shortterm mortality among patients with alcoholic hepatitis.METHODS We retrospectively collected data from 264 patients with clinically diagnosed alcoholic hepatitis from January to December 2013 at 21 academic hospitals in Korea. The performance for predicting short-term mortality was calculated for Chronic Liver FailureSequential Organ Failure Assessment(CLIF-SOFA), CLIF Consortium Organ Failure score(CLIF-C OFs), Maddrey'sdiscriminant function(DF), age, bilirubin, international normalized ratio and creatinine score(ABIC), Glasgow Alcoholic Hepatitis Score(GAHS), model for end-stage liver disease(MELD), and MELD-Na.RESULTS Of 264 patients, 32(12%) patients died within 28 d. The area under receiver operating characteristic curve of CLIF-SOFA, CLIF-C OFs, DF, ABIC, GAHS, MELD, and MELD-Na was 0.86(0.81-0.90), 0.89(0.84-0.92), 0.79(0.74-0.84), 0.78(0.72-0.83), 0.81(0.76-0.86), 0.83(0.78-0.88), and 0.83(0.78-0.88), respectively, for 28-d mortality. The performance of CLIF-SOFA had no statistically significant differences for 28-d mortality. The performance of CLIF-C OFs was superior to that of DF, ABIC, and GAHS, while comparable to that of MELD and MELD-Na in predicting 28-d mortality. A CLIF-SOFA score of 8 had 78.1% sensitivity and 79.7% specificity, and CLIF-C OFs of 10 had 68.8% sensitivity and 91.4% specificity for predicting 28-d mortality.CONCLUSION CLIF-SOFA and CLIF-C OF scores performed well, with comparable predictive ability for short-term mortality compared to the commonly used scoring systems in patients with alcoholic hepatitis.展开更多
目前，人类关于HIV感染的检测项目很多，其中CD4^＋ T淋巴细胞的检测已成为评估HIV感染者疾病状况切实可行和相对经济的检测项目，CD4^＋ T淋巴细胞水平用来监测不同临床阶段HIV感染者免疫状况的变化，判定HIV感染者病程，预测机会性感...目前，人类关于HIV感染的检测项目很多，其中CD4^＋ T淋巴细胞的检测已成为评估HIV感染者疾病状况切实可行和相对经济的检测项目，CD4^＋ T淋巴细胞水平用来监测不同临床阶段HIV感染者免疫状况的变化，判定HIV感染者病程，预测机会性感染的出现以及评价抗HIV药物疗效。从2006年起准确检测CD4^＋ T淋巴细胞计数已经成为判断是否开始治疗AIDS和HIV感染者以及治疗效果观察对比的关键。国际上如美国CDC、英国国家室间质量评价系统（The United Kingdom National External Quality Assessment Service，NEQAS）、加拿大HIV／AIDS质量评价和免疫标准化体系（Quality Assessment and Standardization for Immunological Measures Relevant to HIV／AIDS，QASI）定期发放质控品，展开更多
Defects in craniofacial bones occur congenitally,after high-energy impacts,and during the course of treatment for stroke and cancer.These injuries are difficult to heal due to the overwhelming size of the injury area ...Defects in craniofacial bones occur congenitally,after high-energy impacts,and during the course of treatment for stroke and cancer.These injuries are difficult to heal due to the overwhelming size of the injury area and the inflammatory environment surrounding the injury.Significant inflammatory response after injury may greatly inhibit regenerative healing.We have developed mineralized collagen scaffolds that can induce osteogenic differentiation and matrix biosynthesis in the absence of osteogenic media or supplemental proteins.The amniotic membrane is derived from placentas and has been recently investigated as an extracellular matrix to prevent chronic inflammation.Herein,we hypothesized that a mineralized collagen-amnion composite scaffold could increase osteogenic activity in the presence of inflammatory cytokines.We report mechanical properties of a mineralized collagen-amnion scaffold and investigated osteogenic differentiation and mineral deposition of porcine adipose-derived stem cells within these scaffolds as a function of inflammatory challenge.Incorporation of amniotic membrane matrix promotes osteogenesis similarly to un-modified mineralized collagen scaffolds,and increases in mineralized collagen-amnion scaffolds under inflammatory challenge.Together,these findings suggest that a mineralized collagen-amnion scaffold may provide a beneficial environment to aid craniomaxillofacial bone repair,especially in the course of defects presenting significant inflammatory complications.展开更多
Fabricating non-noble metal-based carbon air electrodes with highly efficient bifunctionality is big challenge owing to the sluggish kinetics of oxygen reduction/evolution reaction(ORR/OER).The efficient cathode catal...Fabricating non-noble metal-based carbon air electrodes with highly efficient bifunctionality is big challenge owing to the sluggish kinetics of oxygen reduction/evolution reaction(ORR/OER).The efficient cathode catalyst is urgently needed to further improve the performance of rechargeable zinc-air batteries.Herein,an activation-doping assisted interface modification strategy is demonstrated based on freestanding integrated carbon composite(CoNiLDH@NPC)composed of wood-based N and P doped active carbon(NPC)and CoNi layer double hydroxides(CoNiLDH).In the light of its large specific surface area and unique defective structure,CoNiLDH@NPC with strong interfacecoupling effect in 2D-3D micro-nanostructure exhibits outstanding bifunctionality.Such carbon composites show half-wave potential of 0.85 V for ORR,overpotential of 320 mV with current density of 10 mA cm^(-2) for OER,and ultra-low gap of 0.70 V.Furthermore,highly-ordered open channels of wood provide enormous space to form abundant triple-phase boundary for accelerating the catalytic process.Consequently,zinc-air batteries using CoNiLDH@NPC show high power density(aqueous:263 mW cm^(-2),quasi-solid-state:65.8 mW cm^(-2))and long-term stability(aqueous:500 h,quasi-solid-state:120 h).This integrated protocol opens a new avenue for the rational design of efficient freestanding air electrode from biomass resources.展开更多
BACKGROUND Corrosive ingestion remains an important global pathology with high morbidity and mortality.Data on the acute management of adult corrosive injuries from sub-Saharan Africa is scarce,with international inve...BACKGROUND Corrosive ingestion remains an important global pathology with high morbidity and mortality.Data on the acute management of adult corrosive injuries from sub-Saharan Africa is scarce,with international investigative algorithms,relying heavily on computed tomography(CT),having limited availability in this setting.AIM To investigate the corrosive injury spectrum in a low-resource setting and the applicability of parameters for predicting full-thickness(FT)necrosis and mortality.METHODS A retrospective analysis of a prospective corrosive injury registry(March 1,2017–October 31,2023)was performed to include all adult patients with acute corrosive ingestion managed at a single,academic referral centre in Cape Town,South Africa.Patient demographics,corrosive ingestion details,initial investigations,management,and short-term outcomes were described using descriptive statistics while multivariate analysis with receiver operator characteristic area under the curve graphs(ROC AUC)were used to identify factors predictive of FT necrosis and 30-day mortality.RESULTS One-hundred patients were included,with a mean age of 32 years(SD:11.2 years)and a male predominance(65.0%).The majority(73.0%)were intentional suicide attempts.Endoscopy on admission was the most frequent initial investigation performed(95 patients),while only 17 were assessed with CT.Seventeen patients had full thickness necrosis at surgery,of which eleven underwent emergency resection and six were palliated.Thirty-day morbidity and mortality were 27.0%and 14.0%,respectively.Patients with full thickness necrosis and those with an established perforation had a 30-day mortality of 58.8%and 91.0%,respectively.Full thickness necrosis was associated with a cumulative 2-year survival of only 17.6%.Multivariate analyses with ROC AUC showed admission endoscopy findings,CT findings,and blood gas findings(pH,base excess,lactate),to all have significant predictive value for full thickness necrosis,with endoscopy proving to have the best predictive value(AUC 0.展开更多
Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HC...Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).展开更多
AIM To evaluate the efficacy and safety of liquid nitrogen cryotherapy as a primary or rescue treatment for BE,with and without dysplasia,or intramucosal adenocarcinoma (IMC).METHODS This was a retrospective,single-ce...AIM To evaluate the efficacy and safety of liquid nitrogen cryotherapy as a primary or rescue treatment for BE,with and without dysplasia,or intramucosal adenocarcinoma (IMC).METHODS This was a retrospective,single-center study carried out in a tertiary care center including 45 patients with BE who was treatment-na?ve or who had persistent intestinal metaplasia(IM),dysplasia,or IMC despite prior therapy.Barrett's mucosa was resected via EMR when clinically appropriate,then patients underwent cryotherapy until eradication or until deemed to have failed treatment.Surveillance biopsies were taken at standard intervals.RESULTS From 2010 through 2014,33 patients were studied regarding the efficacy of cryotherapy.Overall,29 patients (88%) responded to cryotherapy,with 84% having complete regression of all dysplasia and cancer.Complete eradication of cancer and dysplasia was seen in 75% of subjects with IMC; the remaining two subjects did not respond to cryotherapy.Following cryotherapy,15 patients with high-grade dysplasia (HGD) had 30% complete regression,50% IM,and 7% low-grade dysplasia (LGD); one subject had persistent HGD.Complete eradication of dysplasia occurred in all 5 patients with LGD.In 5 patients with IM,complete regression occurred in 4,and IM persisted in one.In 136 cryotherapy sessions amongst 45 patients,adverse events included chest pain (1%),stricture (4%),and one gastrointestinal bleed in a patient on dual antiplatelet therapy who had previously undergone EMR.CONCLUSION Cryotherapy is an efficacious and safe treatment modality for Barrett's esophagus with and without dysplasia or intramucosal adenocarcinoma.展开更多
Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the complex process of mammalian spermatogenesis, male germ cells experience extended periods of the inactiv...Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the complex process of mammalian spermatogenesis, male germ cells experience extended periods of the inactive transcription despite heavy translational requirements for continued growth and differentiation. Hence, spermatogenesis is highly reliant on mechanisms of posttranscriptional regulation of gene expression, facilitated by RNA binding proteins （RBPs）, which remain abundantly expressed throughout this process. One such group of proteins is the Musashi family, previously identified as critical regulators of testis germ cell development and meiosis in Drosophila, and also shown to be vital to sperm development and reproductive potential in the mouse. This review describes the role and function of RBPs our recent knowledge of the Musashi proteins in spermatogenesis. within the scope of male germ cell development, focusing on The functional mechanisms utilized by RBPs within the cell are outlined in depth, and the significance of sub-cellular localization and stage-specific expression in relation to the mode and impact of posttranscriptional regulation is also highlighted. We emphasize the historical role of the Musashi family of RBPs in stem cell function and cell fate determination, as originally characterized in Drosophila and Xenopus, and conclude with our current understanding of the differential roles and functions of the mammalian Musashi proteins, Musashi-1 and Musashi-2, with a primary focus on our findings in spermatogenesis. This review highlights both the essential contribution of RBPs to posttranscriptional regulation and the importance of the Musashi family as master regulators of male gamete development.展开更多
基金Supported by the Science and Technology Planning Project of Guangdong Province,No.2015A030302085 and No.2016A020212022
文摘BACKGROUND Cirrhosis is a chronic late stage liver disease associated with hepatitis viruses,alcoholism, and metabolic disorders, such as Wilson disease(WD). There are no clear markers or clinical features that define cirrhosis originating from these disparate origins. We hypothesized that cirrhosis is not one disease and cirrhosis of different etiology may have differential clinical hepatic features.AIM To delineate the liver features between WD-associated cirrhosis and hepatitis Bassociated cirrhosis in the Chinese population.METHODS In this observational study, we reviewed the medical data of consecutive inpatients who had WD-associated cirrhosis or hepatitis B-associated cirrhosis from January 2010 to August 2018, and excluded patients who had carcinoma,severe heart or pulmonary diseases, or other liver diseases. According to the etiology of cirrhosis, patients were divided into two groups: WD-associated cirrhosis group(60 patients) and hepatitis B-associated cirrhosis group(56 patients). The liver fibrosis degree, liver function indices, and portal hypertension features of these patients were compared between the two groups.RESULTS No inter-group differences were observed in the diagnostic liver fibrosis markers,however, clinical features clearly defined the origin of cirrhosis. WD-associated cirrhosis patients(16-29 years) had lower levels of alanine transaminase,aspartate transaminase, and bilirubin, lower prothrombin time, lower incidence of hepatic encephalopathy, and lower portal vein diameter(P < 0.05), compared to cirrhosis resulting from hepatitis B in older patients(45-62 years). Importantly,they had decreased risks of progression from Child-Pugh grade A to B(odds ratio = 0.046, 95% confidence interval: 0.006-0.387, P = 0.005) and of ascites(odds ratio = 0.08, 95% confidence interval: 0.01-0.48, P = 0.005). Conversely, WDassociated cirrhosis patients had a higher risk of splenomegaly(odds ratio = 4.15,95% confidence interval: 1.38-12.45, P = 0.011).CONCLUSION WD-associated cirrhosis presents a highe
文摘AIM: To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors(PPAR)-δ agonist treatment in nonalcoholic fatty liver disease(NAFLD) models.METHODS: Male C57BL/6J mice were classified according to control or high fat diet(HFD) with or without PPAR-δ agonist(GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide(LPS), HFD + LPS + GW group]. Hep G2 cells were exposed to palmitic acid(PA) and/or LPS in the absence or presence of GW.RESULTS: HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin(IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In Hep G2 cells, PA and LPS treatment markedly increased m RNA of several nucleotide-binding andoligomerization domain-like receptor family members(NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α.CONCLUSION: PPAR-δ agonist reduces fatty acidinduced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.
文摘One of the most common lesions present in the spermatozoa of human infertility patients is an idiopathic failure of sperm-egg recognition. Although this unique cellular interaction can now be readily by-passed by assisted reproductive strategies such as intracytoplasmic sperm injection （ICSI）, recent large-scale epidemiological studies have encouraged the cautious use of this technology and highlighted the need for further research into the mechanisms responsible for defective sperm-egg recognition. Previous work in this field has established that the sperm domains responsible for oocyte interaction are formed during spermatogenesis prior to being dynamically modified during epididymal maturation and capacitation in female reproductive tract. While the factors responsible for the regulation of these sequential maturational events are undoubtedly complex, emerging research has identified the molecular chaperone, heat shock protein A2 （HSPA2）, as a key regulator of these events in human spermatozoa. HSPA2 is a testis-enriched member of the 70 kDa heat shock protein family that promotes the folding, transport, and assembly of protein complexes and has been positively correlated with in vitro fertilization （IVF） success. Furthermore, reduced expression of HSPA2 from the human sperm proteome leads to an impaired capacity for cumulus matrix dispersal, sperm-egg recognition and fertilization following both IVF and ICSI. In this review, we consider the evidence supporting the role of HSPA2 in sperm function and explore the potential mechanisms by which it is depleted in the spermatozoa of infertile patients. Such information offers novel insights into the molecular mechanisms governing sperm function.
基金support from the German Research Foundation DFG(EXC 1003–CiM,TRR61)CRG from the Claude Leon foundationBN from the National Research Foundation of South Africa.
文摘It is well known that the entanglement of a quantum state is invariant under local unitary transformations.This rule dictates,for example,that the entanglement of internal degrees of freedom of a photon remains invariant during free-space propagation.Here,we outline a scenario in which this paradigm does not hold.Using local Bell states engineered from classical vector vortex beams with non-separable degrees of freedom,the so-called classically entangled states,we demonstrate that the entanglement evolves during propagation,oscillating between maximally entangled(purely vector)and product states(purely scalar).We outline the spin–orbit interaction behind these novel propagation dynamics and confirm the results experimentally,demonstrating spin–orbit coupling in paraxial beams.This demonstration highlights a hitherto unnoticed property of classical entanglement and simultaneously offers a device for the on-demand delivery of vector states to targets,for example,for dynamic laser materials processing,switchable resolution within stimulated emission depletion(STED)systems,and a tractor beam for entanglement.
文摘As AI, starting with ChatGPT has become increasingly prevalent in academic discussions, school especially, colleges have become hotspots of AI activities and debates. Colleges have the responsibility of addressing not only the academic, integrity-based concerns of students using AI for their homework, but also as the forebearers of new learning and technology, how AI will change their students’ futures and careers. In this study, we will explore the different factors, such as Computer Science Score and location, that might affect how much a college discusses AI, ChatGPT specifically. To demonstrate the validity of our research, we used self-collected data with our methods detailed below.
基金National Science Foundation International Research Fellowship (0502239)NSERC Discovery Grant (238882 241419)National Science Foundation CAREER award (IOS-0934990)
文摘The environment can impose strong limitations on the efficacy of signal transmission. In particular, for vibratory communication, the signaling environment is often extremely heterogeneous at small scales. Nevertheless, natural selection is expected to select for signals well-suited for effective transmission. Here, we test for substrate-dependent signal efficacy in the wolf spider Schizocosa stridulans Strattou 1991. We first explore the transmission characteristics of this important signaling mo- dality by playing recorded substrate-bome signals through three different substrates （leaf litter, pine litter, and red clay） and measuring the propagated signal. We found that the substrate-bome signal of S. stridulans attenuates the least on leaf litter, the substrate upon which the species is naturally found. Next, by assessing mating success with artificially muted and non-muted males across different signaling substrates （leaf litter, pine litter, and sand）, we explored the relationship between substrate-bome signaling and signaling substrate for mating success. We found that muted males were unsuccessful in obtaining copulations re- gardless of substrate, while mating success was dependent on the signaling substrate for non-muted males. For non-muted males, more males copulated on leaf litter than any other substrate. Taken together, these results confLrm the importance of sub- strate-bome signaling in S. stridulans and suggest a match between signal properties and signal efficacy - leaf litter transmits the signal most effectively and males are most successful in obtaining copulations on leaf litter [Current Zoology 56 （3）： 370-378, 2010].
文摘AIM: To elucidate the question of whether the ocular trauma score(OTS) and the zones of injury could be used as a predictive model of traumatic and post traumatic retinal detachment(RD) in patients with open globe injury(OGI).METHODS: A retrospective observational chart analysis of OGI patients was performed. The collected variables consisted of age, date, gender, time of injury, time until repair, mechanism of injury, zone of injury, injury associated vitreous hemorrhage, trauma associated RD, post traumatic RD, aphakia at injury, periocular trauma and OTS in cases of OGI. RESULTS: Totally 102 patients with traumatic OGI with a minimum of 12 mo follow-up and a median age at of 48.6 y(range: 3-104 y) were identified. Final best corrected visual acuity(BCVA) was independent from the time of repair, yet a statistically significant difference was present between the final BCVA and the zone of injury. Severe trauma presenting with an OTS score Ⅰ(P<0.0001) or Ⅱ(P<0.0001) revealed a significantly worse BCVA at last follow up when compared to the cohort with an OTS score >Ⅲ. OGI associated RD was observed in 36/102 patients(35.3%), whereas post traumatic RD(defined as RD following 14 d after OGI) occurred in 37 patients(36.3%). OGI associated RD did not correlate with the OTS and the zone of injury(P=0.193), yet post traumatic RD correlated significantly with zone Ⅲ injuries(P=0.013). CONCLUSION: The study shows a significant association between lower OTS score and zone Ⅲ injury with lower final BCVA and a higher number of surgeries, but only zone Ⅲ could be significantly associated with a higher rate of RD.
基金Supported by the Korean Association for the Study of the Liver (KASL) and the Korean Liver Foundation
文摘AIM To assess the performance of proposed scores specific for acute-on-chronic liver failure in predicting shortterm mortality among patients with alcoholic hepatitis.METHODS We retrospectively collected data from 264 patients with clinically diagnosed alcoholic hepatitis from January to December 2013 at 21 academic hospitals in Korea. The performance for predicting short-term mortality was calculated for Chronic Liver FailureSequential Organ Failure Assessment(CLIF-SOFA), CLIF Consortium Organ Failure score(CLIF-C OFs), Maddrey'sdiscriminant function(DF), age, bilirubin, international normalized ratio and creatinine score(ABIC), Glasgow Alcoholic Hepatitis Score(GAHS), model for end-stage liver disease(MELD), and MELD-Na.RESULTS Of 264 patients, 32(12%) patients died within 28 d. The area under receiver operating characteristic curve of CLIF-SOFA, CLIF-C OFs, DF, ABIC, GAHS, MELD, and MELD-Na was 0.86(0.81-0.90), 0.89(0.84-0.92), 0.79(0.74-0.84), 0.78(0.72-0.83), 0.81(0.76-0.86), 0.83(0.78-0.88), and 0.83(0.78-0.88), respectively, for 28-d mortality. The performance of CLIF-SOFA had no statistically significant differences for 28-d mortality. The performance of CLIF-C OFs was superior to that of DF, ABIC, and GAHS, while comparable to that of MELD and MELD-Na in predicting 28-d mortality. A CLIF-SOFA score of 8 had 78.1% sensitivity and 79.7% specificity, and CLIF-C OFs of 10 had 68.8% sensitivity and 91.4% specificity for predicting 28-d mortality.CONCLUSION CLIF-SOFA and CLIF-C OF scores performed well, with comparable predictive ability for short-term mortality compared to the commonly used scoring systems in patients with alcoholic hepatitis.
文摘目前，人类关于HIV感染的检测项目很多，其中CD4^＋ T淋巴细胞的检测已成为评估HIV感染者疾病状况切实可行和相对经济的检测项目，CD4^＋ T淋巴细胞水平用来监测不同临床阶段HIV感染者免疫状况的变化，判定HIV感染者病程，预测机会性感染的出现以及评价抗HIV药物疗效。从2006年起准确检测CD4^＋ T淋巴细胞计数已经成为判断是否开始治疗AIDS和HIV感染者以及治疗效果观察对比的关键。国际上如美国CDC、英国国家室间质量评价系统（The United Kingdom National External Quality Assessment Service，NEQAS）、加拿大HIV／AIDS质量评价和免疫标准化体系（Quality Assessment and Standardization for Immunological Measures Relevant to HIV／AIDS，QASI）定期发放质控品，
文摘Defects in craniofacial bones occur congenitally,after high-energy impacts,and during the course of treatment for stroke and cancer.These injuries are difficult to heal due to the overwhelming size of the injury area and the inflammatory environment surrounding the injury.Significant inflammatory response after injury may greatly inhibit regenerative healing.We have developed mineralized collagen scaffolds that can induce osteogenic differentiation and matrix biosynthesis in the absence of osteogenic media or supplemental proteins.The amniotic membrane is derived from placentas and has been recently investigated as an extracellular matrix to prevent chronic inflammation.Herein,we hypothesized that a mineralized collagen-amnion composite scaffold could increase osteogenic activity in the presence of inflammatory cytokines.We report mechanical properties of a mineralized collagen-amnion scaffold and investigated osteogenic differentiation and mineral deposition of porcine adipose-derived stem cells within these scaffolds as a function of inflammatory challenge.Incorporation of amniotic membrane matrix promotes osteogenesis similarly to un-modified mineralized collagen scaffolds,and increases in mineralized collagen-amnion scaffolds under inflammatory challenge.Together,these findings suggest that a mineralized collagen-amnion scaffold may provide a beneficial environment to aid craniomaxillofacial bone repair,especially in the course of defects presenting significant inflammatory complications.
基金financially supported by the National Key Research and Development Program of China(2022YF E0138900)National Natural Science Foundation of China(21972017)+2 种基金the Fundamental Research Funds for the Central Universities(2232022D-18)Shanghai Sailing Program(22YF1400700)the Chenguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission(22CGA37).
文摘Fabricating non-noble metal-based carbon air electrodes with highly efficient bifunctionality is big challenge owing to the sluggish kinetics of oxygen reduction/evolution reaction(ORR/OER).The efficient cathode catalyst is urgently needed to further improve the performance of rechargeable zinc-air batteries.Herein,an activation-doping assisted interface modification strategy is demonstrated based on freestanding integrated carbon composite(CoNiLDH@NPC)composed of wood-based N and P doped active carbon(NPC)and CoNi layer double hydroxides(CoNiLDH).In the light of its large specific surface area and unique defective structure,CoNiLDH@NPC with strong interfacecoupling effect in 2D-3D micro-nanostructure exhibits outstanding bifunctionality.Such carbon composites show half-wave potential of 0.85 V for ORR,overpotential of 320 mV with current density of 10 mA cm^(-2) for OER,and ultra-low gap of 0.70 V.Furthermore,highly-ordered open channels of wood provide enormous space to form abundant triple-phase boundary for accelerating the catalytic process.Consequently,zinc-air batteries using CoNiLDH@NPC show high power density(aqueous:263 mW cm^(-2),quasi-solid-state:65.8 mW cm^(-2))and long-term stability(aqueous:500 h,quasi-solid-state:120 h).This integrated protocol opens a new avenue for the rational design of efficient freestanding air electrode from biomass resources.
文摘BACKGROUND Corrosive ingestion remains an important global pathology with high morbidity and mortality.Data on the acute management of adult corrosive injuries from sub-Saharan Africa is scarce,with international investigative algorithms,relying heavily on computed tomography(CT),having limited availability in this setting.AIM To investigate the corrosive injury spectrum in a low-resource setting and the applicability of parameters for predicting full-thickness(FT)necrosis and mortality.METHODS A retrospective analysis of a prospective corrosive injury registry(March 1,2017–October 31,2023)was performed to include all adult patients with acute corrosive ingestion managed at a single,academic referral centre in Cape Town,South Africa.Patient demographics,corrosive ingestion details,initial investigations,management,and short-term outcomes were described using descriptive statistics while multivariate analysis with receiver operator characteristic area under the curve graphs(ROC AUC)were used to identify factors predictive of FT necrosis and 30-day mortality.RESULTS One-hundred patients were included,with a mean age of 32 years(SD:11.2 years)and a male predominance(65.0%).The majority(73.0%)were intentional suicide attempts.Endoscopy on admission was the most frequent initial investigation performed(95 patients),while only 17 were assessed with CT.Seventeen patients had full thickness necrosis at surgery,of which eleven underwent emergency resection and six were palliated.Thirty-day morbidity and mortality were 27.0%and 14.0%,respectively.Patients with full thickness necrosis and those with an established perforation had a 30-day mortality of 58.8%and 91.0%,respectively.Full thickness necrosis was associated with a cumulative 2-year survival of only 17.6%.Multivariate analyses with ROC AUC showed admission endoscopy findings,CT findings,and blood gas findings(pH,base excess,lactate),to all have significant predictive value for full thickness necrosis,with endoscopy proving to have the best predictive value(AUC 0.
基金partially supported by an investigator-initiated research grant(IN-US-334-4309)from Gilead Sciences to Stanford University.
文摘Background and Aims:As practice patterns and hepatitis C virus(HCV)genotypes(GT)vary geographically,a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal.This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs,focusing on GT3 and GT6.Methods:We analyzed the sustained virological response(SVR12)of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific,North America,and Europe between 07/01/2014–07/01/2021.Results:The mean age was 62±13 years,with 49.6%male.The demographic breakdown was 91.1%Asian(52.9%Japanese,25.7%Chinese/Taiwan residents,5.4%Korean,3.3%Malaysian,and 2.9%Vietnamese),6.4%White,1.3%Hispanic/Latino,and 1%Black/African-American.Additionally,34.8%had cirrhosis,8.6%had hepatocellular carcinoma(HCC),and 24.9%were treatment-experienced(20.7%with interferon,4.3%with direct-acting antivirals).The largest group was GT1(10,246[64.6%]),followed by GT2(3,686[23.2%]),GT3(1,151[7.2%]),GT6(457[2.8%]),GT4(47[0.3%]),GT5(1[0.006%]),and untyped GTs(261[1.6%]).The overall SVR12 was 96.9%,with rates over 95%for GT1/2/3/6 but 91.5%for GT4.SVR12 for GT3 was 95.1%overall,98.2%for GT3a,and 94.0%for GT3b.SVR12 was 98.3%overall for GT6,lower for patients with cirrhosis and treatment-experienced(TE)(93.8%)but≥97.5%for tretment-naive patients regardless of cirrhosis status.On multivariable analysis,advanced age,prior treatment failure,cirrhosis,active HCC,and GT3/4 were independent predictors of lower SVR12,while being Asian was a significant predictor of achieving SVR12.Conclusions:In this diverse multinational realworld cohort of patients with various GTs,the overall cure rate was 96.9%,despite large numbers of patients with cirrhosis,HCC,TE,and GT3/6.SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent(>91%).
文摘AIM To evaluate the efficacy and safety of liquid nitrogen cryotherapy as a primary or rescue treatment for BE,with and without dysplasia,or intramucosal adenocarcinoma (IMC).METHODS This was a retrospective,single-center study carried out in a tertiary care center including 45 patients with BE who was treatment-na?ve or who had persistent intestinal metaplasia(IM),dysplasia,or IMC despite prior therapy.Barrett's mucosa was resected via EMR when clinically appropriate,then patients underwent cryotherapy until eradication or until deemed to have failed treatment.Surveillance biopsies were taken at standard intervals.RESULTS From 2010 through 2014,33 patients were studied regarding the efficacy of cryotherapy.Overall,29 patients (88%) responded to cryotherapy,with 84% having complete regression of all dysplasia and cancer.Complete eradication of cancer and dysplasia was seen in 75% of subjects with IMC; the remaining two subjects did not respond to cryotherapy.Following cryotherapy,15 patients with high-grade dysplasia (HGD) had 30% complete regression,50% IM,and 7% low-grade dysplasia (LGD); one subject had persistent HGD.Complete eradication of dysplasia occurred in all 5 patients with LGD.In 5 patients with IM,complete regression occurred in 4,and IM persisted in one.In 136 cryotherapy sessions amongst 45 patients,adverse events included chest pain (1%),stricture (4%),and one gastrointestinal bleed in a patient on dual antiplatelet therapy who had previously undergone EMR.CONCLUSION Cryotherapy is an efficacious and safe treatment modality for Barrett's esophagus with and without dysplasia or intramucosal adenocarcinoma.
文摘Controlled gene regulation during gamete development is vital for maintaining reproductive potential. During the complex process of mammalian spermatogenesis, male germ cells experience extended periods of the inactive transcription despite heavy translational requirements for continued growth and differentiation. Hence, spermatogenesis is highly reliant on mechanisms of posttranscriptional regulation of gene expression, facilitated by RNA binding proteins （RBPs）, which remain abundantly expressed throughout this process. One such group of proteins is the Musashi family, previously identified as critical regulators of testis germ cell development and meiosis in Drosophila, and also shown to be vital to sperm development and reproductive potential in the mouse. This review describes the role and function of RBPs our recent knowledge of the Musashi proteins in spermatogenesis. within the scope of male germ cell development, focusing on The functional mechanisms utilized by RBPs within the cell are outlined in depth, and the significance of sub-cellular localization and stage-specific expression in relation to the mode and impact of posttranscriptional regulation is also highlighted. We emphasize the historical role of the Musashi family of RBPs in stem cell function and cell fate determination, as originally characterized in Drosophila and Xenopus, and conclude with our current understanding of the differential roles and functions of the mammalian Musashi proteins, Musashi-1 and Musashi-2, with a primary focus on our findings in spermatogenesis. This review highlights both the essential contribution of RBPs to posttranscriptional regulation and the importance of the Musashi family as master regulators of male gamete development.
