Acute pancreatitis (AP) is a rare event in pregnancy, occurring in approximately 3 in 10 000 pregnancies. The spectrum of AP in pregnancy ranges from mild pancreatitis to serious pancreatitis associated with necrosis,...Acute pancreatitis (AP) is a rare event in pregnancy, occurring in approximately 3 in 10 000 pregnancies. The spectrum of AP in pregnancy ranges from mild pancreatitis to serious pancreatitis associated with necrosis, abscesses, pseudocysts and multiple organ dysfunction syndromes. Pregnancy related hematological and biochemical alterations infl uence the interpretation of diagnostic tests and assessment of severity of AP. As in any other disease associated with pregnancy, AP is associated with greater concerns as it deals with two lives rather than just one as in the non-pregnant population. The recent advances in clinical gastroenterology have improved the early diagnosis and effective management of biliary pancreatitis. Diagnostic studies such as endoscopic ultrasound, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography and therapeutic modalities that include endoscopic sphincterotomy, biliary stenting, common bile duct stone extraction and laparoscopic cholecystectomy are major milestones in gastroenterology. When properly managed AP in pregnancy does not carry a dismal prognosis as in the past.展开更多
Acute pancreatitis in its severe form is complicated by multiple organ system dysfunction, most importantly by pulmonary complications which include hypoxia, acute respiratory distress syndrome, atelectasis, and pleur...Acute pancreatitis in its severe form is complicated by multiple organ system dysfunction, most importantly by pulmonary complications which include hypoxia, acute respiratory distress syndrome, atelectasis, and pleural effusion. The pathogenesis of some of the above complications is attributed to the production of noxious cytokines. Clinically significant is the early onset of pleural effusion, which heralds a poor outcome of acute pancreatitis. The role of circulating trypsin, phospholipase A2, platelet activating factor, release of free fatty acids, chemoattractants such as tumor necrsosis factor （TNF）- alpha, interleukin （IL）-1, IL-6, IL-8, fMet-leu-phe （a bacterial wall product）, nitric oxide, substance P, and macrophage inhlbitor factor is currently studied. The hope is that future management of acute pancreatitis with a better understanding of the pathogenesis of lung injury will be directed against the production of noxious cytokines.展开更多
Low back pain(LBP),as a leading cause of disability,is a common musculoskeletal disorder that results in major social and economic burdens.Recent research has identified inflammation and related signaling pathways as ...Low back pain(LBP),as a leading cause of disability,is a common musculoskeletal disorder that results in major social and economic burdens.Recent research has identified inflammation and related signaling pathways as important factors in the onset and progression of disc degeneration,a significant contributor to LBP.Inflammatory mediators also play an indispensable role in discogenic LBP.The suppression of LBP is a primary goal of clinical practice but has not received enough attention in disc research studies.Here,an overview of the advances in inflammation-related pain in disc degeneration is provided,with a discussion on the role of inflammation in IVD degeneration and pain induction.Puncture models,mechanical models,and spontaneous models as the main animal models to study painful disc degeneration are discussed,and the underlying signaling pathways are summarized.Furthermore,potential drug candidates,either under laboratory investigation or undergoing clinical trials,to suppress discogenic LBP by eliminating inflammation are explored.We hope to attract more research interest to address inflammation and pain in IDD and contribute to promoting more translational research.展开更多
The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical te...The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive （second generation） biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials （third generation） are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental ＂origin＂ require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.展开更多
Currently, a large proportion of global fossil fuel emissions originate from large point sources such as power generation or industrial processes. This trend is expected to continue until the year 2030 and beyond. Car...Currently, a large proportion of global fossil fuel emissions originate from large point sources such as power generation or industrial processes. This trend is expected to continue until the year 2030 and beyond. Carbon capture and storage （CCS）, a straightforward and effective carbon reduction approach, will play a significant role in reducing emissions from these sources into the future if atmospheric carbon dioxide （CO2） emissions are to be stabilized and global warming limited below a threshold of 2 ℃. This review provides an update on the status of large scale integrated CCS technologies using solvent absorption for CO2 capture and provides an insight into the development of new solvents, including advanced amine solvents, amino acid salts, carbonate systems, aqueous ammonia, immiscible liquids and ionic liquids. These proposed new solvents aim to reduce the overall cost CO2 capture by improving the CO2 absorption rate, CO2 capture capacity, thereby reducing equipment size and decreasing the energy required for solvent regeneration.展开更多
The Basidiomycota constitutes a major phylum of the kingdom Fungi and is second in species numbers to the Ascomycota.The present work provides an overview of all validly published,currently used basidiomycete genera t...The Basidiomycota constitutes a major phylum of the kingdom Fungi and is second in species numbers to the Ascomycota.The present work provides an overview of all validly published,currently used basidiomycete genera to date in a single document.An outline of all genera of Basidiomycota is provided,which includes 1928 currently used genera names,with 1263 synonyms,which are distributed in 241 families,68 orders,18 classes and four subphyla.We provide brief notes for each accepted genus including information on classification,number of accepted species,type species,life mode,habitat,distribution,and sequence information.Furthermore,three phylogenetic analyses with combined LSU,SSU,5.8s,rpb1,rpb2,and ef1 datasets for the subphyla Agaricomycotina,Pucciniomycotina and Ustilaginomycotina are conducted,respectively.Divergence time estimates are provided to the family level with 632 species from 62 orders,168 families and 605 genera.Our study indicates that the divergence times of the subphyla in Basidiomycota are 406-430 Mya,classes are 211-383 Mya,and orders are 99-323 Mya,which are largely consistent with previous studies.In this study,all phylogenetically supported families were dated,with the families of Agaricomycotina diverging from 27-178 Mya,Pucciniomycotina from 85-222 Mya,and Ustilaginomycotina from 79-177 Mya.Divergence times as additional criterion in ranking provide additional evidence to resolve taxonomic problems in the Basidiomycota taxonomic system,and also provide a better understanding of their phylogeny and evolution.展开更多
The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A...The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PlGF), play important roles in vascular biology in both normal physiology and pathology. The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab, also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target. Other members of the VEGF family are now being targeted, and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic. Here, we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.展开更多
AIM： To analyze the prevalence of gastroesophageal reflux disease （GERD） related symptoms in patients with diabetes mellitus （DM） and to find out the relationship between diabetic neuropathy and the prevalence of...AIM： To analyze the prevalence of gastroesophageal reflux disease （GERD） related symptoms in patients with diabetes mellitus （DM） and to find out the relationship between diabetic neuropathy and the prevalence of GERD symptoms. METHODS： In this prospective questionnaire study, 150 consecutive type 2 diabetic patients attending the endocrine clinic were enrolled. A junior physician helped the patients to understand the questions. Patients were asked about the presence of five most frequent symptoms of GERD that included heartburn （at least 1/wk）, regurgitation, chest pain, hoarseness of voice and chronic cough. Patients with past medical history of angina, COPD, asthma, cough due to ACEI or preexisting GERD prior to onset of diabetes and apparent psychiatric disorders were excluded from the survey. We further divided the patients into two groups based on presence or absence of peripheral neuropathy. Out of 150 patients, 46 had neuropathy, whereas 104 patients did not have neuropathy. Data are expressed as mean ± SD, and number of patients in each category and percentage of total patients in that group. Normal distributions between groups were compared with Student t test and the prevalence rates between groups were compared with Chi-square tests for significance. RESULTS： The average duration of diabetes were 12 ± 9.2 years and the average HbAlc level of this group was 7.7% ± 2.0%. The mean weight and BMI were 198 ± 54 Ibs. and 32 ± 7.2 kg/m^2. Forty percent （61/150） patients reported having at least one of the symptoms of GERD and thirty percent （45/150） reported having heartburn at least once a week. The prevalence of GERD symptoms is higher in patients with neuropathy than patients without neuropathy （58.7% vs 32.7%, P 〈 0.01）. The prevalence of heartburn, chest pain and chronic cough are also higher in patients with neuropathy than in patients without neuropathy （43.5% vs 24%; 10.9% vs 4.8% and 17.8% vs 6.7% respectively, P 〈 0.05）. CONCLUSION： The prevalence of GER展开更多
Objective To review and assess the update studies regarding selective serotonin reuptake inhibitors （SSRIs） in the treatment of premature ejaculation （PE） and then provide practical recommendations and possible me...Objective To review and assess the update studies regarding selective serotonin reuptake inhibitors （SSRIs） in the treatment of premature ejaculation （PE） and then provide practical recommendations and possible mechanisms concerning state of the art knowledge for the use of SSRIs in alleviating PE. Data sources Using the Medline, 48 articles published from January 1st, 1996 to August 1st, 2006 concerning the use of SSRIs and their possible mechanisms in alleviating PE were found and reviewed. Study selection PE, rapid ejaculation, early ejaculation and SSRIs were employed as the keywords, and relevant articles about the use of SSRIs and their possible mechanisms in the treatment of PE were selected. Results Many kinds of SSRIs, such as fluoxetine, sertraline, paroxetine and citalopram, have widely been employed to treat PE. However, their effects are moderate and there is no a universal agreement about the kind, dose, protocol and duration. Dapoxetine, as the first prescription treatment of PE, may change this bottle-neck situation. SSRIs are suggested to be used in young men with lifelong PE, and acquired PE when etiological factors are removed but PE still exists. Phosphodiesterase 5 inhibitors （PDE5-ls） are suggested to be employed alone or combined with SSRIs when SSRIs fail to treat PE or sexual dysfunction associated with SSRIs occurs. The protocol of taking drugs on demand based on taking them daily for a suitable period is proposed to be chosen firstly. The possible mechanisms include increasing serotonergic neurotransmission and activating 5-hydroxytryptamine 2C （5-HT2c） receptors, then switching the ejaculatory threshold to a higher level, decreasing the penile sensitivity and their own effect of antidepression. Conclusion The efficacies of the current SSRIs are moderate in the treatment of PE and they have not been approved by the FDA, therefore new SSRI like dapoxetine needs to be further evaluated.展开更多
Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer(GC)and its premalignant states from gross histological models to increasingly precise molecular descriptions.In th...Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer(GC)and its premalignant states from gross histological models to increasingly precise molecular descriptions.In this review we reflect upon the historic approaches to describing premalignant lesions and GC,highlight the current molecular landscape and how this could inform future risk assessment prevention strategies.展开更多
Nonalcoholic fatty liver disease (NAFLD) is a hepatic mani-festation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countrie...Nonalcoholic fatty liver disease (NAFLD) is a hepatic mani-festation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney trans-plantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as these patients are generally older, obese and more likely to have a number of metabolic risk factors. Bariatric surgery is an option and can be considered if a structured weight loss program does not achieve the sustained weight loss goal. Comprehensive cardiovascular risk assessment and aggres-sive management of comorbid conditions are crucial in the LT evaluation process to improve post-transplant survival. Re-current nonalcoholic steatohepatitis after LT is not uncom-mon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts.展开更多
Light fidelity(LiFi),which is emerging as a compelling technology paradigm shifting the common means of highcapacity wireless communication technologies,requires wearable and full-duplex compact design because of its ...Light fidelity(LiFi),which is emerging as a compelling technology paradigm shifting the common means of highcapacity wireless communication technologies,requires wearable and full-duplex compact design because of its great significance in smart wearables as well as the‘Internet of Things’.However,the construction of the key component of wearable full-duplex LiFi,light-emitting/detecting bifunctional fibres,is still challenging because of the conflicting process between carrier separation and recombination,as well as the highly dynamic film-forming process.Here,we demonstrate light-emitting/detecting bifunctional fibres enabled by perovskite QDs with hybrid components.The hybrid perovskite inks endow fibres with super-smooth QD films.This,combined with the small exciton binding energy and high carrier mobility of perovskite QDs,enables successful integration of electroluminescence and photodetection into monofilaments.The bifunctional fibres possess the narrowest electroluminescence full width at half maximum of ~19 nm and,more importantly,the capability for simultaneously transmitting and receiving information.The successful fabrication of narrow emission full-duplex LiFi fibres paves the way for the fabrication and integration of low crosstalk interoperable smart wearables.展开更多
Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how ...Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer cells.We found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T cells.The coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX complex.Additionally,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer cells.Through our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T cells.Moreover,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.展开更多
Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strat...Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza- specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses （T cells and antibody-producing B cells） achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T- cells （MAIT cells, y~ T cells, and NKT cells） in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and γδ T cells as well as adaptive CD8＋ and CD4＋ T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.展开更多
Like the wars predating the First World War where human foot soldiers were deemed tools in the battlefield against an enemy, so too are the host immune cells of a patient battling a malignant gastric cancer. Indeed, t...Like the wars predating the First World War where human foot soldiers were deemed tools in the battlefield against an enemy, so too are the host immune cells of a patient battling a malignant gastric cancer. Indeed, the tumour microenvironment resembles a battlefield, where the patient's immune cells are the defence against invading tumour cells. However, the relationship between different immune components of the host response to cancer is more complex than an "us against them" model. Components of the immune system inadvertently work against the interests of the host and become pro-tumourigenic while other components soldier on against the common enemy – the tumour cell.展开更多
Autoimmune encephalitis is a poorly understood condition that can present with a combination of neurological and psychiatric symptoms, either of which may predominate. There are many autoantibodies associated with a v...Autoimmune encephalitis is a poorly understood condition that can present with a combination of neurological and psychiatric symptoms, either of which may predominate. There are many autoantibodies associated with a variety of clinical syndromes-anti-N-Methyl-D-Aspartate receptor(NMDAR) is the commonest. Currently, the most widely used therapy is prompt plasmapheresis and steroid treatment(and tumour resection if indicated), followed by second line immunosuppression if this fails. Given the growing awareness of autoimmune encephalitis as an entity, it is increasingly important that we consider it as a potential diagnosis in order to provide timely, effective treatment. We discuss several previously published case reports and one new case. These reports examined the effects of electroconvulsive therapy(ECT) on patients with autoimmune encephalitis, particularly those in whom psychiatric symptoms are especially debilitating and refractory to standard treatment. We also discuss factors predicting good outcome and possible mechanisms by which ECT may be effective. Numerous cases, such as those presented by Wingfield, Tsutsui, Florance, Sansing, Braakman and Matsumoto, demonstrate effective use of ECT in anti-NMDAR encephalitis patients with severe psychiatric symptoms such as catatonia, psychosis, narcolepsy and stupor who had failed to respond to standard treatments alone. We also present a new case of a 71-year-old female who presented to a psychiatric unit initially with depression, which escalated to catatonia, delusions, nihilism and auditory hallucinations. After anti-NMDAR antibodies were isolated, she was treated by the neurology team with plasmapheresis and steroids, with a partial response. She received multiple sessions of ECT and her psychiatric symptoms completely resolved and she returned to her premorbid state. For this reason, we suggest that ECT should be considered, particularly in those patients who are non-responders to standard therapies.展开更多
Ribosome biogenesis and protein synthesis are fundamental rate-limiting steps for cell growth and proliferation.The ribosomal proteins(RPs),comprising the structural parts of the ribosome,are essential for ribosome as...Ribosome biogenesis and protein synthesis are fundamental rate-limiting steps for cell growth and proliferation.The ribosomal proteins(RPs),comprising the structural parts of the ribosome,are essential for ribosome assembly and function.In addition to their canonical ribosomal functions,multiple RPs have extra-ribosomal functions including activation of p53-dependent or p53-independent pathways in response to stress,resulting in cell cycle arrest and apoptosis.Defects in ribosome biogenesis,translation,and the functions of individual RPs,including mutations in RPs have been linked to a diverse range of human congenital disorders termed ribosomopathies.Ribosomopathies are characterized by tissue-specific phenotypic abnormalities and higher cancer risk later in life.Recent discoveries of somatic mutations in RPs in multiple tumor types reinforce the connections between ribosomal defects and cancer.In this article,we review the most recent advances in understanding the molecular consequences of RP mutations and ribosomal defects in ribosomopathies and cancer.We particularly discuss the molecular basis of the transition from hypo-to hyper-proliferation in ribosomopathies with elevated cancer risk,a paradox termed"Dameshek's riddle."Furthermore,we review the current treatments for ribosomopathies and prospective therapies targeting ribosomal defects.We also highlight recent advances in ribosome stress-based cancer therapeutics.Importantly,insights into the mechanisms of resistance to therapies targeting ribosome biogenesis bring new perspectives into the molecular basis of cancer susceptibility in ribosomopathies and new clinical implications for cancer therapy.展开更多
Cell death is an essential biological process for physiological growth and development.Three classical forms of cell death—apoptosis,autophagy,and necrosis—display distinct morphological features by activating speci...Cell death is an essential biological process for physiological growth and development.Three classical forms of cell death—apoptosis,autophagy,and necrosis—display distinct morphological features by activating specific signaling pathways.With recent research advances,we have started to appreciate that these cell death processes can cross-talk through interconnecting,even overlapping,signaling pathways,and the final cell fate is the result of the interplay of different cell death programs.This review provides an insight into the independence of and associations among these three types of cell death and explores the significance of cell death under the specific conditions of human diseases,particularly neurodegenerative diseases and cancer.展开更多
文摘Acute pancreatitis (AP) is a rare event in pregnancy, occurring in approximately 3 in 10 000 pregnancies. The spectrum of AP in pregnancy ranges from mild pancreatitis to serious pancreatitis associated with necrosis, abscesses, pseudocysts and multiple organ dysfunction syndromes. Pregnancy related hematological and biochemical alterations infl uence the interpretation of diagnostic tests and assessment of severity of AP. As in any other disease associated with pregnancy, AP is associated with greater concerns as it deals with two lives rather than just one as in the non-pregnant population. The recent advances in clinical gastroenterology have improved the early diagnosis and effective management of biliary pancreatitis. Diagnostic studies such as endoscopic ultrasound, magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography and therapeutic modalities that include endoscopic sphincterotomy, biliary stenting, common bile duct stone extraction and laparoscopic cholecystectomy are major milestones in gastroenterology. When properly managed AP in pregnancy does not carry a dismal prognosis as in the past.
文摘Acute pancreatitis in its severe form is complicated by multiple organ system dysfunction, most importantly by pulmonary complications which include hypoxia, acute respiratory distress syndrome, atelectasis, and pleural effusion. The pathogenesis of some of the above complications is attributed to the production of noxious cytokines. Clinically significant is the early onset of pleural effusion, which heralds a poor outcome of acute pancreatitis. The role of circulating trypsin, phospholipase A2, platelet activating factor, release of free fatty acids, chemoattractants such as tumor necrsosis factor （TNF）- alpha, interleukin （IL）-1, IL-6, IL-8, fMet-leu-phe （a bacterial wall product）, nitric oxide, substance P, and macrophage inhlbitor factor is currently studied. The hope is that future management of acute pancreatitis with a better understanding of the pathogenesis of lung injury will be directed against the production of noxious cytokines.
基金the National Natural Science Foundation of China(81772386,81702191,81572175,81371984,and 81071511)the Guangdong-Hong Kong Joint Innovation Project of Guangdong Province(2017A050506019)the Natural Science Foundation of Guangdong Province,China(2020A1515011031).
文摘Low back pain(LBP),as a leading cause of disability,is a common musculoskeletal disorder that results in major social and economic burdens.Recent research has identified inflammation and related signaling pathways as important factors in the onset and progression of disc degeneration,a significant contributor to LBP.Inflammatory mediators also play an indispensable role in discogenic LBP.The suppression of LBP is a primary goal of clinical practice but has not received enough attention in disc research studies.Here,an overview of the advances in inflammation-related pain in disc degeneration is provided,with a discussion on the role of inflammation in IVD degeneration and pain induction.Puncture models,mechanical models,and spontaneous models as the main animal models to study painful disc degeneration are discussed,and the underlying signaling pathways are summarized.Furthermore,potential drug candidates,either under laboratory investigation or undergoing clinical trials,to suppress discogenic LBP by eliminating inflammation are explored.We hope to attract more research interest to address inflammation and pain in IDD and contribute to promoting more translational research.
文摘The role of Bone Tissue Engineering in the field of Regenerative Medicine has been the topic of substantial research over the past two decades. Technological advances have improved orthopaedic implants and surgical techniques for bone reconstruction. However, improvements in surgical techniques to reconstruct bone have been limited by the paucity of autologous materials available and donor site morbidity. Recent advances in the development of biomaterials have provided attractive alternatives to bone grafting expanding the surgical options for restoring the form and function of injured bone. Specifically, novel bioactive （second generation） biomaterials have been developed that are characterised by controlled action and reaction to the host tissue environment, whilst exhibiting controlled chemical breakdown and resorption with an ultimate replacement by regenerating tissue. Future generations of biomaterials （third generation） are designed to be not only osteo- conductive but also osteoinductive, i.e. to stimulate regeneration of host tissues by combining tissue engineer- ing and in situ tissue regeneration methods with a focus on novel applications. These techniques will lead to novel possibilities for tissue regeneration and repair. At present, tissue engineered constructs that may find future use as bone grafts for complex skeletal defects, whether from post-traumatic, degenerative, neoplastic or congenital/developmental ＂origin＂ require osseous reconstruction to ensure structural and functional integrity. Engineering functional bone using combinations of cells, scaffolds and bioactive factors is a promising strategy and a particular feature for future development in the area of hybrid materials which are able to exhibit suitable biomimetic and mechanical properties. This review will discuss the state of the art in this field and what we can expect from future generations of bone regeneration concepts.
文摘Currently, a large proportion of global fossil fuel emissions originate from large point sources such as power generation or industrial processes. This trend is expected to continue until the year 2030 and beyond. Carbon capture and storage （CCS）, a straightforward and effective carbon reduction approach, will play a significant role in reducing emissions from these sources into the future if atmospheric carbon dioxide （CO2） emissions are to be stabilized and global warming limited below a threshold of 2 ℃. This review provides an update on the status of large scale integrated CCS technologies using solvent absorption for CO2 capture and provides an insight into the development of new solvents, including advanced amine solvents, amino acid salts, carbonate systems, aqueous ammonia, immiscible liquids and ionic liquids. These proposed new solvents aim to reduce the overall cost CO2 capture by improving the CO2 absorption rate, CO2 capture capacity, thereby reducing equipment size and decreasing the energy required for solvent regeneration.
基金National Key R&D Program of China(Project No.2018YFD0400200)the National Natural Science Foundation of China(Project IDs:31470152,31360014 and 31970010)+18 种基金Beijing Innovative Consortium of Agriculture Research System(Project ID:BAIC05-2019)the Thailand Research funds for grant RDG6130001 entitled"Impact of climate change on fungal diversity and biogeography in the Greater Mekong Subregion"Thailand Science Research and Innovation fund for the grant DBG6280009 entitled Macrofungi diversity research from the Lancang-Mekong Watershed and surrounding areasCroatian Science Foundation for support under the project For FungiDNA(IP-2018-01-1736)the support provided by the Moravian Museum by the Ministry of Culture of the Czech Republic as part of its long-term conceptual development programme for research institutions[Grant Number DKRVO,Ref.MK000094862]National Natural Science Foundation of China(31270072)the Special Funds for the Young Scholars of Taxonomy of the Chinese Academy of Sciences(ZSBR-001)National Key Basic Research Special Foundation of China(2013FY110400)support from the Department of Science&Technology(DST),New Delhi,Indiain the form of a DST-Inspire Faculty Fellowship(DST/INSPIRE/04/2018/001906,dated 24 July,2018)State task of the V.L.Komarov Botanical Institute of the Russian Academy of Sciences(AAAA-A19-119080990059-1 and RFBR,project 19-04-00024)the National Natural Science Foundation of China(Nos.30770013,31500013)the National Project on Scientific Ground work for Basic Science of the Ministry of Science and Technology(Nos.2012FY1116002014FY210400)the Coordenacao de Aperfeic¸oamento de Pessoal de Nivel Superior(CAPES-Brazil)for the PhD scholarshipsCNPq for providing‘Produtividade em Pesquisa’(Proc.307922/2014-6 and Proc.307947/2017-3)grantCONACYT(Project 252934)COFAAIPN(Project SIP-20195222)the financial support provided for his researchesthe Coordenacao de Aperfeic¸oamento de Pessoal de Nivel Superior(CAPES-Brazil)for the PhD scholarshipsthe following sources of funding for his A
文摘The Basidiomycota constitutes a major phylum of the kingdom Fungi and is second in species numbers to the Ascomycota.The present work provides an overview of all validly published,currently used basidiomycete genera to date in a single document.An outline of all genera of Basidiomycota is provided,which includes 1928 currently used genera names,with 1263 synonyms,which are distributed in 241 families,68 orders,18 classes and four subphyla.We provide brief notes for each accepted genus including information on classification,number of accepted species,type species,life mode,habitat,distribution,and sequence information.Furthermore,three phylogenetic analyses with combined LSU,SSU,5.8s,rpb1,rpb2,and ef1 datasets for the subphyla Agaricomycotina,Pucciniomycotina and Ustilaginomycotina are conducted,respectively.Divergence time estimates are provided to the family level with 632 species from 62 orders,168 families and 605 genera.Our study indicates that the divergence times of the subphyla in Basidiomycota are 406-430 Mya,classes are 211-383 Mya,and orders are 99-323 Mya,which are largely consistent with previous studies.In this study,all phylogenetically supported families were dated,with the families of Agaricomycotina diverging from 27-178 Mya,Pucciniomycotina from 85-222 Mya,and Ustilaginomycotina from 79-177 Mya.Divergence times as additional criterion in ranking provide additional evidence to resolve taxonomic problems in the Basidiomycota taxonomic system,and also provide a better understanding of their phylogeny and evolution.
基金funded partly by a program grant from the National Health and Medical Research Council of Australia(NH&MRC)supported by Senior Research Fellowships from the NH&MRCsupport of the Pfizer Australia Fellowship
文摘The vascular endothelial growth factor (VEGF) family of soluble protein growth factors consists of key mediators of angiogenesis and lymphangiogenesis in the context of tumor biology. The members of the family, VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and placenta growth factor (PlGF), play important roles in vascular biology in both normal physiology and pathology. The generation of a humanized neutralizing antibody to VEGF-A (bevacizumab, also known as Avastin) and the demonstration of its benefit in numerous human cancers have confirmed the merit of an anti-angiogenesis approach to cancer treatment and have validated the VEGF-A signaling pathway as a therapeutic target. Other members of the VEGF family are now being targeted, and their relevance to human cancer and the development of resistance to anti-VEGF-A treatment are being evaluated in the clinic. Here, we discuss the potential of targeting VEGF family members in the diagnosis and treatment of cancer.
文摘AIM： To analyze the prevalence of gastroesophageal reflux disease （GERD） related symptoms in patients with diabetes mellitus （DM） and to find out the relationship between diabetic neuropathy and the prevalence of GERD symptoms. METHODS： In this prospective questionnaire study, 150 consecutive type 2 diabetic patients attending the endocrine clinic were enrolled. A junior physician helped the patients to understand the questions. Patients were asked about the presence of five most frequent symptoms of GERD that included heartburn （at least 1/wk）, regurgitation, chest pain, hoarseness of voice and chronic cough. Patients with past medical history of angina, COPD, asthma, cough due to ACEI or preexisting GERD prior to onset of diabetes and apparent psychiatric disorders were excluded from the survey. We further divided the patients into two groups based on presence or absence of peripheral neuropathy. Out of 150 patients, 46 had neuropathy, whereas 104 patients did not have neuropathy. Data are expressed as mean ± SD, and number of patients in each category and percentage of total patients in that group. Normal distributions between groups were compared with Student t test and the prevalence rates between groups were compared with Chi-square tests for significance. RESULTS： The average duration of diabetes were 12 ± 9.2 years and the average HbAlc level of this group was 7.7% ± 2.0%. The mean weight and BMI were 198 ± 54 Ibs. and 32 ± 7.2 kg/m^2. Forty percent （61/150） patients reported having at least one of the symptoms of GERD and thirty percent （45/150） reported having heartburn at least once a week. The prevalence of GERD symptoms is higher in patients with neuropathy than patients without neuropathy （58.7% vs 32.7%, P 〈 0.01）. The prevalence of heartburn, chest pain and chronic cough are also higher in patients with neuropathy than in patients without neuropathy （43.5% vs 24%; 10.9% vs 4.8% and 17.8% vs 6.7% respectively, P 〈 0.05）. CONCLUSION： The prevalence of GER
文摘Objective To review and assess the update studies regarding selective serotonin reuptake inhibitors （SSRIs） in the treatment of premature ejaculation （PE） and then provide practical recommendations and possible mechanisms concerning state of the art knowledge for the use of SSRIs in alleviating PE. Data sources Using the Medline, 48 articles published from January 1st, 1996 to August 1st, 2006 concerning the use of SSRIs and their possible mechanisms in alleviating PE were found and reviewed. Study selection PE, rapid ejaculation, early ejaculation and SSRIs were employed as the keywords, and relevant articles about the use of SSRIs and their possible mechanisms in the treatment of PE were selected. Results Many kinds of SSRIs, such as fluoxetine, sertraline, paroxetine and citalopram, have widely been employed to treat PE. However, their effects are moderate and there is no a universal agreement about the kind, dose, protocol and duration. Dapoxetine, as the first prescription treatment of PE, may change this bottle-neck situation. SSRIs are suggested to be used in young men with lifelong PE, and acquired PE when etiological factors are removed but PE still exists. Phosphodiesterase 5 inhibitors （PDE5-ls） are suggested to be employed alone or combined with SSRIs when SSRIs fail to treat PE or sexual dysfunction associated with SSRIs occurs. The protocol of taking drugs on demand based on taking them daily for a suitable period is proposed to be chosen firstly. The possible mechanisms include increasing serotonergic neurotransmission and activating 5-hydroxytryptamine 2C （5-HT2c） receptors, then switching the ejaculatory threshold to a higher level, decreasing the penile sensitivity and their own effect of antidepression. Conclusion The efficacies of the current SSRIs are moderate in the treatment of PE and they have not been approved by the FDA, therefore new SSRI like dapoxetine needs to be further evaluated.
文摘Over the last two decades there has been a broad paradigm shift in our understanding of gastric cancer(GC)and its premalignant states from gross histological models to increasingly precise molecular descriptions.In this review we reflect upon the historic approaches to describing premalignant lesions and GC,highlight the current molecular landscape and how this could inform future risk assessment prevention strategies.
文摘Nonalcoholic fatty liver disease (NAFLD) is a hepatic mani-festation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney trans-plantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as these patients are generally older, obese and more likely to have a number of metabolic risk factors. Bariatric surgery is an option and can be considered if a structured weight loss program does not achieve the sustained weight loss goal. Comprehensive cardiovascular risk assessment and aggres-sive management of comorbid conditions are crucial in the LT evaluation process to improve post-transplant survival. Re-current nonalcoholic steatohepatitis after LT is not uncom-mon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts.
基金financially supported by NSFC(51922049,61725402,61604074)the National Key Research and Development Program of China(2016YFB0401701)+4 种基金the Natural Science Foundation of Jiangsu Province(BK20180020)the Fundamental Research Funds for the Central Universities(30917011202)PAPD of Jiangsu Higher Education Institutionsthe National‘ten thousand talents plan’leading talents(No.W03020394)the Six top talent innovation teams of Jiangsu Province(No.TD-XCL-004).
文摘Light fidelity(LiFi),which is emerging as a compelling technology paradigm shifting the common means of highcapacity wireless communication technologies,requires wearable and full-duplex compact design because of its great significance in smart wearables as well as the‘Internet of Things’.However,the construction of the key component of wearable full-duplex LiFi,light-emitting/detecting bifunctional fibres,is still challenging because of the conflicting process between carrier separation and recombination,as well as the highly dynamic film-forming process.Here,we demonstrate light-emitting/detecting bifunctional fibres enabled by perovskite QDs with hybrid components.The hybrid perovskite inks endow fibres with super-smooth QD films.This,combined with the small exciton binding energy and high carrier mobility of perovskite QDs,enables successful integration of electroluminescence and photodetection into monofilaments.The bifunctional fibres possess the narrowest electroluminescence full width at half maximum of ~19 nm and,more importantly,the capability for simultaneously transmitting and receiving information.The successful fabrication of narrow emission full-duplex LiFi fibres paves the way for the fabrication and integration of low crosstalk interoperable smart wearables.
基金funding from the National Science Foundation of China(31930016)the Peking-Tsinghua Center for Life Sciences+4 种基金ZW received funding from the State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases(2024KF00001)the National Science Foundation of China(82350119)CCW received funding from the Talent Introduction Funds from the Chinese Academy of Medical Science(2022-RC310-10)the National Science Foundation of China(32150005)the Research Funds from Health@InnoHK Program,launched by the Innovation Technology Commission of the Hong Kong Special Administrative Region.
文摘Vγ9Vδ2 T cells are specialized effector cells that have gained prominence as immunotherapy agents due to their ability to target and kill cells with altered pyrophosphate metabolites.In our effort to understand how cancer cells evade the cell-killing activity of Vγ9Vδ2 T cells,we performed a comprehensive genome-scale CRISPR screening of cancer cells.We found that four molecules belonging to the butyrophilin(BTN)family,specifically BTN2A1,BTN3A1,BTN3A2,and BTN3A3,are critically important and play unique,nonoverlapping roles in facilitating the destruction of cancer cells by primary Vγ9Vδ2 T cells.The coordinated function of these BTN molecules was driven by synchronized gene expression,which was regulated by IFN-γsignaling and the RFX complex.Additionally,an enzyme called QPCTL was shown to play a key role in modifying the N-terminal glutamine of these BTN proteins and was found to be a crucial factor in Vγ9Vδ2 T cell killing of cancer cells.Through our research,we offer a detailed overview of the functional genomic mechanisms that underlie how cancer cells escape Vγ9Vδ2 T cells.Moreover,our findings shed light on the importance of the harmonized expression and function of gene family members in modulating T-cell activity.
文摘Influenza is a major global health problem, causing infections of the respiratory tract, often leading to acute pneumonia, life-threatening complications and even deaths. Over the last seven decades, vaccination strategies have been utilized to protect people from complications of influenza, especially groups at high risk of severe disease. While current vaccination regimens elicit strain-specific antibody responses, they fail to generate cross-protection against seasonal, pandemic and avian viruses. Moreover, vaccines designed to generate influenza- specific T-cell responses are yet to be optimized. During natural infection, viral replication is initially controlled by innate immunity before adaptive immune responses （T cells and antibody-producing B cells） achieve viral clearance and host recovery. Adaptive T and B cells maintain immunological memory and provide protection against subsequent infections with related influenza viruses. Recent studies also shed light on the role of innate T- cells （MAIT cells, y~ T cells, and NKT cells） in controlling influenza and linking innate and adaptive immune mechanisms, thus making them attractive targets for vaccination strategies. We summarize the current knowledge on influenza-specific innate MAIT and γδ T cells as well as adaptive CD8＋ and CD4＋ T cells, and discuss how these responses can be harnessed by novel vaccine strategies to elicit cross-protective immunity against different influenza strains and subtypes.
文摘Like the wars predating the First World War where human foot soldiers were deemed tools in the battlefield against an enemy, so too are the host immune cells of a patient battling a malignant gastric cancer. Indeed, the tumour microenvironment resembles a battlefield, where the patient's immune cells are the defence against invading tumour cells. However, the relationship between different immune components of the host response to cancer is more complex than an "us against them" model. Components of the immune system inadvertently work against the interests of the host and become pro-tumourigenic while other components soldier on against the common enemy – the tumour cell.
文摘Autoimmune encephalitis is a poorly understood condition that can present with a combination of neurological and psychiatric symptoms, either of which may predominate. There are many autoantibodies associated with a variety of clinical syndromes-anti-N-Methyl-D-Aspartate receptor(NMDAR) is the commonest. Currently, the most widely used therapy is prompt plasmapheresis and steroid treatment(and tumour resection if indicated), followed by second line immunosuppression if this fails. Given the growing awareness of autoimmune encephalitis as an entity, it is increasingly important that we consider it as a potential diagnosis in order to provide timely, effective treatment. We discuss several previously published case reports and one new case. These reports examined the effects of electroconvulsive therapy(ECT) on patients with autoimmune encephalitis, particularly those in whom psychiatric symptoms are especially debilitating and refractory to standard treatment. We also discuss factors predicting good outcome and possible mechanisms by which ECT may be effective. Numerous cases, such as those presented by Wingfield, Tsutsui, Florance, Sansing, Braakman and Matsumoto, demonstrate effective use of ECT in anti-NMDAR encephalitis patients with severe psychiatric symptoms such as catatonia, psychosis, narcolepsy and stupor who had failed to respond to standard treatments alone. We also present a new case of a 71-year-old female who presented to a psychiatric unit initially with depression, which escalated to catatonia, delusions, nihilism and auditory hallucinations. After anti-NMDAR antibodies were isolated, she was treated by the neurology team with plasmapheresis and steroids, with a partial response. She received multiple sessions of ECT and her psychiatric symptoms completely resolved and she returned to her premorbid state. For this reason, we suggest that ECT should be considered, particularly in those patients who are non-responders to standard therapies.
基金This work was supported by the National Health and Medical Research Council(NHMRC)of Australia(Project grants#1053792 and#1162052)Cancer Council Victoria Project Grant#1184873+1 种基金R.B.P was supported by Senior Research NHMRC Fellowship#1058586E.S.is supported by a Victorian Cancer Agency Mid-Career Research Fellowship(MCRF19007).
文摘Ribosome biogenesis and protein synthesis are fundamental rate-limiting steps for cell growth and proliferation.The ribosomal proteins(RPs),comprising the structural parts of the ribosome,are essential for ribosome assembly and function.In addition to their canonical ribosomal functions,multiple RPs have extra-ribosomal functions including activation of p53-dependent or p53-independent pathways in response to stress,resulting in cell cycle arrest and apoptosis.Defects in ribosome biogenesis,translation,and the functions of individual RPs,including mutations in RPs have been linked to a diverse range of human congenital disorders termed ribosomopathies.Ribosomopathies are characterized by tissue-specific phenotypic abnormalities and higher cancer risk later in life.Recent discoveries of somatic mutations in RPs in multiple tumor types reinforce the connections between ribosomal defects and cancer.In this article,we review the most recent advances in understanding the molecular consequences of RP mutations and ribosomal defects in ribosomopathies and cancer.We particularly discuss the molecular basis of the transition from hypo-to hyper-proliferation in ribosomopathies with elevated cancer risk,a paradox termed"Dameshek's riddle."Furthermore,we review the current treatments for ribosomopathies and prospective therapies targeting ribosomal defects.We also highlight recent advances in ribosome stress-based cancer therapeutics.Importantly,insights into the mechanisms of resistance to therapies targeting ribosome biogenesis bring new perspectives into the molecular basis of cancer susceptibility in ribosomopathies and new clinical implications for cancer therapy.
基金This work was supported by grants from the National Natural Science Foundation of China(Nos.81770176 and 31470071)the New Century 151 Talent Project of Zhejiang Province,the 521 Talent Foundation of Zhejiang Sci-Tech University,and the Open Foundation from Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province(No.ZJZLSYS004)The funders played no role in the study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Cell death is an essential biological process for physiological growth and development.Three classical forms of cell death—apoptosis,autophagy,and necrosis—display distinct morphological features by activating specific signaling pathways.With recent research advances,we have started to appreciate that these cell death processes can cross-talk through interconnecting,even overlapping,signaling pathways,and the final cell fate is the result of the interplay of different cell death programs.This review provides an insight into the independence of and associations among these three types of cell death and explores the significance of cell death under the specific conditions of human diseases,particularly neurodegenerative diseases and cancer.
