Rheumatoid arthritis（RA） is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A...Rheumatoid arthritis（RA） is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages：（i） triggering,（ii） maturation,（iii） targeting, and（iv） fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies（including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs） remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA.展开更多
AIM： To detect the new serum biomarkers for colorectal cancer （CRC） by serum protein profiling with surfaceenhanced laser desorption ionisation - time of flight mass spectrometry （SELDI-TOF MS）. METHODS： Two ind...AIM： To detect the new serum biomarkers for colorectal cancer （CRC） by serum protein profiling with surfaceenhanced laser desorption ionisation - time of flight mass spectrometry （SELDI-TOF MS）. METHODS： Two independent serum sample sets were analysed separately with the ProteinChip technology （set A： 40 CRC ＋ 49 healthy controls; set B： 37 CRC ＋ 31 healthy controls）, using chips with a weak cation exchange moiety and buffer pH 5. Discriminative power of differentially expressed proteins was assessed with a classification tree algorithm. Sensitivities and specificities of the generated classification trees were obtained by blindly applying data from set A to the generated trees from set B and vice versa. CRC serum protein profiles were also compared with those from breast, ovarian, prostate, and non-small cell lung cancer. RESULTS： Mass-to-charge ratios （m/z） 3.1×10^3, 3.3× 10^3, 4.5×10^3, 6.6×10^3 and 28×10^3 were used as classitiers in the best-performing classification trees. Tree sensitivities and specificities were between 65% and 90%.Host of these discriminative m/z values were also different in the other tumour types investigated. M/z 3.3× 10^3, main classifier in most trees, was a doubly charged form of the 6.6× 10^3-Da protein. The latter was identified as apolipoprotein C-I. M/z 3.1×10^3 was identified as an N-terminal fragment of albumin, and m/z 28× 10^3 as apolipoprotein A-I. CONCLUSION： SELDI-TOF MS followed by classification tree pattern analysis is a suitable technique for finding new serum markers for CRC. Biomarkers can be identified and reproducibly detected in independent sample sets with high sensitivities and specificities. Although not specific for CRC, these biomarkers have a potential role in disease and treatment monitoring.展开更多
The synthesis of two-dimensional （2D） layered materials with controllable thickness is of considerable interest for diverse applications. Here we report the first chemical vapor deposition growth of single- and few-...The synthesis of two-dimensional （2D） layered materials with controllable thickness is of considerable interest for diverse applications. Here we report the first chemical vapor deposition growth of single- and few-layer MoSe2 nanosheets. By using Se and MoO3 as the chemical vapor supply, we demonstrate that highly crystalline MoSe2 can be directly grown on the 300 nm SiO2/Si substrates to form optically distinguishable single- and multi-layer nanosheets, typically in triangular shaped domains with edge lengths around 30 btm, which can merge into continuous thin films upon further growth. Micro-Raman spectroscopy and imaging was used to probe the thickness-dependent vibrational properties. Photoluminescence spectroscopy demonstrates that MoSe2 monolayers exhibit strong near band edge emission at 1.55 eV, while bilayers or multi-layers exhibit much weaker emission, indicating of the transition to a direct band gap semiconductor as the thickness is reduced to a monolayer.展开更多
Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancrea...Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pan-creatitis characterized by marked stroma formation with a high number of infiltrating granulocytes(such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells(PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in pro-moting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways(i.e., Transforming growth factor-β/SMAD, mitogen--activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin(IL)-1, IL-1β, IL-6, IL--8 IL-10, IL-18, IL--33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for pancreatic pathogenesis.展开更多
This review provides an overview of the literature regarding heterogeneous molecular catalysts for electrochemical CO2 reduction (ECR).Fundamental aspects of the science,including aggregation,electrochemical rate laws...This review provides an overview of the literature regarding heterogeneous molecular catalysts for electrochemical CO2 reduction (ECR).Fundamental aspects of the science,including aggregation,electrochemical rate laws,and electrode-catalyst electronic coupling,are discussed to provide a solid foundation on which to design experiments and interpret results.Mechanistic aspects of ECR are presented based on electrokinetic and spectroscopic measurements as well as density functional theory (DFT) calculations.Consensus is improving for electrokinetic measurements,but the redox state of the metal center under reaction conditions and DFT reaction pathways lack agreement in the literature.Concerning the tunable aspects of the molecular catalyst,the impacts of the metal center,ligand substituents,and electrode support on the activity and selectivity toward ECR are presented with an emphasis on those studies that controlled for aggregation and minimized mass-transport limitations.Extended three-dimensional (3D) structures such as polymers,metal-organic frameworks (MOFs),and covalent-organic frameworks (COFs) are discussed as highly tunable architectures that begin to mimic the catalytic pockets of enzyme active sites.To achieve the full potential of these catalysts,design principles must emerge based on a combination of deconvoluting measurements to extract intrinsic catalyst properties and more reliable theoretical calculations to predict reaction pathways.展开更多
Acute kidney injury(AKI),associated with significant mor-bidity and mortality,is widely known to involve epithelial apoptosis,excessive inflammation,and fibrosis in re-sponse to ischemia or reperfusion injury,which re...Acute kidney injury(AKI),associated with significant mor-bidity and mortality,is widely known to involve epithelial apoptosis,excessive inflammation,and fibrosis in re-sponse to ischemia or reperfusion injury,which results in either chronic pathological changes or death.Therefore,it is imperative that investigations are conducted in order to fi nd effective,early diagnoses,and therapeutic targets needed to help prevent and treat AKI.However,the mech-anisms modulating the pathogenesis of AKI still remain largely undetermined.MicroRNAs(miRNAs),small non-coding RNA molecules,play an important role in several fundamental biological and pathological processes by a post transcriptional regulatory function of gene expres-sion.MicroRNA-21(miR-21)is a recently identifi ed,typi-cal miRNA that is functional as a regulator known to be involved in apoptosis as well as inflammatory and fi brotic signaling pathways in AKI.As a result,miR-21 is now considered a novel biomarker when diagnosing and treat-ing AKI.This article reviews the correlative literature and research progress regarding the roles of miR-21 in AKI.展开更多
Aims Environmental gradients are drivers of species diversity;however,we know relatively little about the evolutionary processes underlying these relationships.A potentially powerful approach to studying diversity gra...Aims Environmental gradients are drivers of species diversity;however,we know relatively little about the evolutionary processes underlying these relationships.A potentially powerful approach to studying diversity gradients is to quantify the phylogenetic structure within and between assemblages arrayed along broad spatial and environmental gradients.Here,we evaluate the phylogenetic structure of plant assemblages along an environmental gradient with the expectation that the habitat specialization of entire lineages is an important evolutionary pattern influencing the structure of tree communities along environmental gradients.Methods We evaluated the effect of several environmental variables on the phylogenetic structure of plant assemblages in 145 plots distributed in northwestern South America that cover a broad environmental gradient.The phylogenetic alpha diversity was quantified for each plot and the phylogenetic beta diversity between each pair of plots was also quantified.Both the alpha and beta diversity measures were then related to spatial and environmental gradients in the study system.Important Findings We found that gradients in temperature and potential evapotranspiration have a strong relationship with the phylogenetic alpha diversity in our study system,with phylogenetic overdispersion in low temperatures and phylogenetic clustering at higher temperatures.Further,the phylogenetic beta diversity between two plots increases with an increasing difference in temperature,whereas annual precipitation was not a significant predictor of community phylogenetic turnover.We also found that the phylogenetic structure of the plots in our study system was related to the degree of seasonal flooding and seasonality in precipitation.In particular,more stressful environments such as dry forests and flooded forests showed phylogenetic clustering.Finally,in contrast with previous studies,we find that phylogenetic beta diversity was not strongly related to the spatial distance separating two forest plots,which may be展开更多
The mechanisms that promote liver injury in non-alcoholic fatty liver disease(NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required....The mechanisms that promote liver injury in non-alcoholic fatty liver disease(NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required. Iron has been widely implicated in the pathogenesis of NAFLD and represents a potential target for treatment. Relationships between serum ferritin concentration and NAFLD are noted in a majority of studies, although serum ferritin is an imprecise measure of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in NAFLD have been demonstrated in animal and cell culture models. However, the human data linking hepatic iron to liver injury in NAFLD is less clear, with seemingly conflicting evidence, supporting either an effect of iron in hepatocytes or within reticulo-endothelial cells. Adipose tissue has emerged as a key site at which iron may have a pathogenic role in NAFLD. Evidence for this comes indirectly from studies that have evaluated the role of adipose tissue iron with respect to insulin resistance. Adding further complexity, multiple strands of evidence support an effect of NAFLD itself on iron metabolism. In this review, we summarise the human and basic science data that has evaluated the role of iron in NAFLD pathogenesis.展开更多
Coronal shear fractures of the distal humerus are rare,complex fractures that can be technically challenging to manage. They usually result from a low-energy fall and direct compression of the distal humerus by the ra...Coronal shear fractures of the distal humerus are rare,complex fractures that can be technically challenging to manage. They usually result from a low-energy fall and direct compression of the distal humerus by the radial head in a hyper-extended or semi-flexed elbow or from spontaneous reduction of a posterolateral subluxation or dislocation. Due to the small number of soft tissue attachments at this site, almost all of these fractures are displaced. The incidence of distal humeral coronal shear fractures is higher among women because of the higher rate of osteoporosis in women and the difference in carrying angle between men and women. Distal humeral coronal shear fractures may occur in isolation, may be part of a complex elbow injury, or may be associated with injuries proximal or distal to the elbow. An associated lateral collateral ligament injury is seen in up to 40% and an associated radial head fracture is seen in up to 30% of these fractures. Given the complex nature of distal humeral coronal shear fractures, there is preference for operative management. Operative fixation leads to stable anatomic reduction, restores articular congruity, and allows initiation of early range-of-motion movements in the majority of cases. Several surgical exposure and fixation techniques are available to reconstruct the articular surface fol owing distal humeral coronal shear fractures. The lateral extensile approach and fixation with countersunk headless compression screws placed in an anterior-to-posterior fashion are commonly used. We have found a two-incision approach(direct anterior and lateral) that results in less soft tissue dissection and better outcomes than the lateral extensile approach in our experience. Stiffness, pain, articular incongruity, arthritis, and ulnohumeral instability may result if reduction is non-anatomic or if fixation fails.展开更多
Mitochondrial processes play an important role in tumor initiation and progression.In this review,we focus on three critical processes by which mitochondrial function may contribute to cancer:through alterations in gl...Mitochondrial processes play an important role in tumor initiation and progression.In this review,we focus on three critical processes by which mitochondrial function may contribute to cancer:through alterations in glucose metabolism,the production of reactive oxygen species (ROS) and compromise of intrinsic apoptotic function.Alterations in cancer glucose metabolism include the Warburg effect,leading to a shift in metabolism away from aerobic respiration toward glycolysis,even when sufficient oxygen is present to support respiration.Such alterations in cellular metabolism may favor tumor cell growth by increasing the availability of biosynthetic intermediates needed for cellular growth and proliferation.Mutations in specific metabolic enzymes,namely succinate dehydrogenase,fumarate hydratase and the isocitrate dehydrogenases,have been linked to human cancer.Mitochondrial ROS may contribute to cancer via DNA damage and the activation of aberrant signaling pathways.ROS-dependent stabilization of the transcription factor hypoxia-inducible factor (HIF) may be a particularly important event for tumorigenesis.Compromised function of intrinsic apoptosis removes an important cellular safeguard against cancer and has been implicated in tumorigenesis,tumor metastasis,and chemoresistance.Each of the major mitochondrial processes is linked.In this review,we outline the connections between them and address ways these mitochondrial pathways may be targeted for cancer therapy.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
Traumatic optic neuropathy:Traumatic brain injury is one of the leading causes of disability and mortality in the United States.It impacts people of all ages and demographics,particularly younger males and members of ...Traumatic optic neuropathy:Traumatic brain injury is one of the leading causes of disability and mortality in the United States.It impacts people of all ages and demographics,particularly younger males and members of the military.Vision loss is commonly associated with traumatic brain injuries of all severities and can leave patients permanently disabled.This vision loss can be caused by injury to the visual system at multiple levels,including the eyes,optic nerves,and many different sites in the brain and brainstem(Sen,2017).Despite the far-reaching effects of visual impairment after traumatic brain injury,its incidence after traumatic brain injury is not well measured,and few successful treatments have been identified or implemented.展开更多
Use of extracorporeal membrane oxygenation to support patients with critical cardiorespiratory illness is increasing.Systemic anticoagulation is an essential element in the care of extracorporeal membrane oxygenation ...Use of extracorporeal membrane oxygenation to support patients with critical cardiorespiratory illness is increasing.Systemic anticoagulation is an essential element in the care of extracorporeal membrane oxygenation patients.While unfractionated heparin is the most commonly used agent,unfractionated heparin is associated with several unique complications that can be catastrophic in critically ill patients,including heparin-induced thrombocytopenia and acquired antithrombin deficiency.These complications can result in thrombotic events and subtherapeutic anticoagulation.Direct thrombin inhibitors(DTIs)are emerging as alternative anticoagulants in patients supported by extracorporeal membrane oxygenation.Increasing evidence supports DTIs use as safe and effective in extracorporeal membrane oxygenation patients with and without heparininduced thrombocytopenia.This review outlines the pharmacology,dosing strategies and available protocols,monitoring parameters,and special use considerations for all available DTIs in extracorporeal membrane oxygenation patients.The advantages and disadvantages of DTIs in extracorporeal membrane oxygenation relative to unfractionated heparin will be described.展开更多
Lesions of the rotator cuff(RC) are a common occurrence affecting millions of people across all parts of the globe. RC tears are also rampantly prevalent with an agedependent increase in numbers. Other associated fact...Lesions of the rotator cuff(RC) are a common occurrence affecting millions of people across all parts of the globe. RC tears are also rampantly prevalent with an agedependent increase in numbers. Other associated factors include a history of trauma, limb dominance, contralateral shoulder, smoking-status, hypercholesterolemia, posture and occupational dispositions. The challenge lies in early diagnosis since a high proportion of patients are asymptomatic. Pain and decreasing shoulder power and function should alert the heedful practitioner in recognizing promptly the onset or aggravation of existing RC tears. Partial-thickness tears(PTT) can be bursalsided or articular-sided tears. Over the course of time, PTT enlarge and propagate into full-thickness tears(FTT) and develop distinct chronic pathological changes due to muscle retraction, fatty infiltration and muscle atrophy. These lead to a reduction in tendon elasticity and viability. Eventually, the glenohumeral joint experiences a series of degenerative alterations- cuff tear arthropathy. To avert this, a vigilant clinician must utilize and corroborate clinical skill and radiological findings to identify tear progression. Modern radio-diagnostic means of ultrasonography and magnetic resonance imaging provide excellent visualization of structural details and are crucial in determining further course of action for these patients. Physical therapy along with activity modifications, antiinflammatory and analgesic medications form the pillars of nonoperative treatment. Elderly patients with minimal functional demands can be managed conservatively and reassessed at frequent intervals. Regular monitoring helps in isolating patients who require surgical interventions. Early surgery should be considered in younger, active and symptomatic, healthy patients. In addition to being costeffective, this helps in providing a functional shoulder witha stable cuff. An easily reproducible technique of maximal strength and sturdiness should by chosen among the armamentarium of the 展开更多
Neurodegenerative diseases are a group of neuronal disorders caused by progressive neuronal cell death in different regions of the human brain.Alzheimer's disease(AD)and Parkinson's disease(PD)are the most com...Neurodegenerative diseases are a group of neuronal disorders caused by progressive neuronal cell death in different regions of the human brain.Alzheimer's disease(AD)and Parkinson's disease(PD)are the most common types of neurodegenerative diseases that affect millions of people worldwide.There is no cure available for either disease.One of the pathological hallmarks of neurodegenerative diseases is the abnormal protein aggregation in the central nervous system.展开更多
The electrochemical basis for understanding the interaction of thiol collectors with sulfide minerals is reviewed. Spectroscopic techniques are being increasingly applied to augment electrochemical studies and provide...The electrochemical basis for understanding the interaction of thiol collectors with sulfide minerals is reviewed. Spectroscopic techniques are being increasingly applied to augment electrochemical studies and provide unequivocal identification of species formed at mineral surfaces in flotation systems. These include X ray photoelectron, Fourier transform infrared spectroscopy and, more recently, surface enhanced Raman scattering spectroscopy. The progress that has been made in the application of electrochemical measurement to monitor and control flotation plants is also considered.展开更多
基金supported in part by the Australian National Health and Medical Research Council (NHMRC, No. 1107828)Arthritis foundation of Australiathe University of Western Australia Research Collaboration Awards
文摘Rheumatoid arthritis（RA） is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages：（i） triggering,（ii） maturation,（iii） targeting, and（iv） fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies（including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs） remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA.
文摘AIM： To detect the new serum biomarkers for colorectal cancer （CRC） by serum protein profiling with surfaceenhanced laser desorption ionisation - time of flight mass spectrometry （SELDI-TOF MS）. METHODS： Two independent serum sample sets were analysed separately with the ProteinChip technology （set A： 40 CRC ＋ 49 healthy controls; set B： 37 CRC ＋ 31 healthy controls）, using chips with a weak cation exchange moiety and buffer pH 5. Discriminative power of differentially expressed proteins was assessed with a classification tree algorithm. Sensitivities and specificities of the generated classification trees were obtained by blindly applying data from set A to the generated trees from set B and vice versa. CRC serum protein profiles were also compared with those from breast, ovarian, prostate, and non-small cell lung cancer. RESULTS： Mass-to-charge ratios （m/z） 3.1×10^3, 3.3× 10^3, 4.5×10^3, 6.6×10^3 and 28×10^3 were used as classitiers in the best-performing classification trees. Tree sensitivities and specificities were between 65% and 90%.Host of these discriminative m/z values were also different in the other tumour types investigated. M/z 3.3× 10^3, main classifier in most trees, was a doubly charged form of the 6.6× 10^3-Da protein. The latter was identified as apolipoprotein C-I. M/z 3.1×10^3 was identified as an N-terminal fragment of albumin, and m/z 28× 10^3 as apolipoprotein A-I. CONCLUSION： SELDI-TOF MS followed by classification tree pattern analysis is a suitable technique for finding new serum markers for CRC. Biomarkers can be identified and reproducibly detected in independent sample sets with high sensitivities and specificities. Although not specific for CRC, these biomarkers have a potential role in disease and treatment monitoring.
文摘The synthesis of two-dimensional （2D） layered materials with controllable thickness is of considerable interest for diverse applications. Here we report the first chemical vapor deposition growth of single- and few-layer MoSe2 nanosheets. By using Se and MoO3 as the chemical vapor supply, we demonstrate that highly crystalline MoSe2 can be directly grown on the 300 nm SiO2/Si substrates to form optically distinguishable single- and multi-layer nanosheets, typically in triangular shaped domains with edge lengths around 30 btm, which can merge into continuous thin films upon further growth. Micro-Raman spectroscopy and imaging was used to probe the thickness-dependent vibrational properties. Photoluminescence spectroscopy demonstrates that MoSe2 monolayers exhibit strong near band edge emission at 1.55 eV, while bilayers or multi-layers exhibit much weaker emission, indicating of the transition to a direct band gap semiconductor as the thickness is reduced to a monolayer.
基金Supported by National Institutes of Health,Nos.R01 DK067255 and R01 AI080581
文摘Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pan-creatitis characterized by marked stroma formation with a high number of infiltrating granulocytes(such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells(PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in pro-moting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways(i.e., Transforming growth factor-β/SMAD, mitogen--activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin(IL)-1, IL-1β, IL-6, IL--8 IL-10, IL-18, IL--33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for pancreatic pathogenesis.
文摘This review provides an overview of the literature regarding heterogeneous molecular catalysts for electrochemical CO2 reduction (ECR).Fundamental aspects of the science,including aggregation,electrochemical rate laws,and electrode-catalyst electronic coupling,are discussed to provide a solid foundation on which to design experiments and interpret results.Mechanistic aspects of ECR are presented based on electrokinetic and spectroscopic measurements as well as density functional theory (DFT) calculations.Consensus is improving for electrokinetic measurements,but the redox state of the metal center under reaction conditions and DFT reaction pathways lack agreement in the literature.Concerning the tunable aspects of the molecular catalyst,the impacts of the metal center,ligand substituents,and electrode support on the activity and selectivity toward ECR are presented with an emphasis on those studies that controlled for aggregation and minimized mass-transport limitations.Extended three-dimensional (3D) structures such as polymers,metal-organic frameworks (MOFs),and covalent-organic frameworks (COFs) are discussed as highly tunable architectures that begin to mimic the catalytic pockets of enzyme active sites.To achieve the full potential of these catalysts,design principles must emerge based on a combination of deconvoluting measurements to extract intrinsic catalyst properties and more reliable theoretical calculations to predict reaction pathways.
文摘Acute kidney injury(AKI),associated with significant mor-bidity and mortality,is widely known to involve epithelial apoptosis,excessive inflammation,and fibrosis in re-sponse to ischemia or reperfusion injury,which results in either chronic pathological changes or death.Therefore,it is imperative that investigations are conducted in order to fi nd effective,early diagnoses,and therapeutic targets needed to help prevent and treat AKI.However,the mech-anisms modulating the pathogenesis of AKI still remain largely undetermined.MicroRNAs(miRNAs),small non-coding RNA molecules,play an important role in several fundamental biological and pathological processes by a post transcriptional regulatory function of gene expres-sion.MicroRNA-21(miR-21)is a recently identifi ed,typi-cal miRNA that is functional as a regulator known to be involved in apoptosis as well as inflammatory and fi brotic signaling pathways in AKI.As a result,miR-21 is now considered a novel biomarker when diagnosing and treat-ing AKI.This article reviews the correlative literature and research progress regarding the roles of miR-21 in AKI.
文摘Aims Environmental gradients are drivers of species diversity;however,we know relatively little about the evolutionary processes underlying these relationships.A potentially powerful approach to studying diversity gradients is to quantify the phylogenetic structure within and between assemblages arrayed along broad spatial and environmental gradients.Here,we evaluate the phylogenetic structure of plant assemblages along an environmental gradient with the expectation that the habitat specialization of entire lineages is an important evolutionary pattern influencing the structure of tree communities along environmental gradients.Methods We evaluated the effect of several environmental variables on the phylogenetic structure of plant assemblages in 145 plots distributed in northwestern South America that cover a broad environmental gradient.The phylogenetic alpha diversity was quantified for each plot and the phylogenetic beta diversity between each pair of plots was also quantified.Both the alpha and beta diversity measures were then related to spatial and environmental gradients in the study system.Important Findings We found that gradients in temperature and potential evapotranspiration have a strong relationship with the phylogenetic alpha diversity in our study system,with phylogenetic overdispersion in low temperatures and phylogenetic clustering at higher temperatures.Further,the phylogenetic beta diversity between two plots increases with an increasing difference in temperature,whereas annual precipitation was not a significant predictor of community phylogenetic turnover.We also found that the phylogenetic structure of the plots in our study system was related to the degree of seasonal flooding and seasonality in precipitation.In particular,more stressful environments such as dry forests and flooded forests showed phylogenetic clustering.Finally,in contrast with previous studies,we find that phylogenetic beta diversity was not strongly related to the spatial distance separating two forest plots,which may be
文摘The mechanisms that promote liver injury in non-alcoholic fatty liver disease(NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required. Iron has been widely implicated in the pathogenesis of NAFLD and represents a potential target for treatment. Relationships between serum ferritin concentration and NAFLD are noted in a majority of studies, although serum ferritin is an imprecise measure of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in NAFLD have been demonstrated in animal and cell culture models. However, the human data linking hepatic iron to liver injury in NAFLD is less clear, with seemingly conflicting evidence, supporting either an effect of iron in hepatocytes or within reticulo-endothelial cells. Adipose tissue has emerged as a key site at which iron may have a pathogenic role in NAFLD. Evidence for this comes indirectly from studies that have evaluated the role of adipose tissue iron with respect to insulin resistance. Adding further complexity, multiple strands of evidence support an effect of NAFLD itself on iron metabolism. In this review, we summarise the human and basic science data that has evaluated the role of iron in NAFLD pathogenesis.
文摘Coronal shear fractures of the distal humerus are rare,complex fractures that can be technically challenging to manage. They usually result from a low-energy fall and direct compression of the distal humerus by the radial head in a hyper-extended or semi-flexed elbow or from spontaneous reduction of a posterolateral subluxation or dislocation. Due to the small number of soft tissue attachments at this site, almost all of these fractures are displaced. The incidence of distal humeral coronal shear fractures is higher among women because of the higher rate of osteoporosis in women and the difference in carrying angle between men and women. Distal humeral coronal shear fractures may occur in isolation, may be part of a complex elbow injury, or may be associated with injuries proximal or distal to the elbow. An associated lateral collateral ligament injury is seen in up to 40% and an associated radial head fracture is seen in up to 30% of these fractures. Given the complex nature of distal humeral coronal shear fractures, there is preference for operative management. Operative fixation leads to stable anatomic reduction, restores articular congruity, and allows initiation of early range-of-motion movements in the majority of cases. Several surgical exposure and fixation techniques are available to reconstruct the articular surface fol owing distal humeral coronal shear fractures. The lateral extensile approach and fixation with countersunk headless compression screws placed in an anterior-to-posterior fashion are commonly used. We have found a two-incision approach(direct anterior and lateral) that results in less soft tissue dissection and better outcomes than the lateral extensile approach in our experience. Stiffness, pain, articular incongruity, arthritis, and ulnohumeral instability may result if reduction is non-anatomic or if fixation fails.
基金supported by Award Numbers R01CA138651 and R01CA138651S1 to J.P. MacKeigan and V.C. Fogg
文摘Mitochondrial processes play an important role in tumor initiation and progression.In this review,we focus on three critical processes by which mitochondrial function may contribute to cancer:through alterations in glucose metabolism,the production of reactive oxygen species (ROS) and compromise of intrinsic apoptotic function.Alterations in cancer glucose metabolism include the Warburg effect,leading to a shift in metabolism away from aerobic respiration toward glycolysis,even when sufficient oxygen is present to support respiration.Such alterations in cellular metabolism may favor tumor cell growth by increasing the availability of biosynthetic intermediates needed for cellular growth and proliferation.Mutations in specific metabolic enzymes,namely succinate dehydrogenase,fumarate hydratase and the isocitrate dehydrogenases,have been linked to human cancer.Mitochondrial ROS may contribute to cancer via DNA damage and the activation of aberrant signaling pathways.ROS-dependent stabilization of the transcription factor hypoxia-inducible factor (HIF) may be a particularly important event for tumorigenesis.Compromised function of intrinsic apoptosis removes an important cellular safeguard against cancer and has been implicated in tumorigenesis,tumor metastasis,and chemoresistance.Each of the major mitochondrial processes is linked.In this review,we outline the connections between them and address ways these mitochondrial pathways may be targeted for cancer therapy.
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supported by NIH grant HD001097(to NKE)by a Cincinnati Children’s Hospital Procter Scholar Award(to NKE)
文摘Traumatic optic neuropathy:Traumatic brain injury is one of the leading causes of disability and mortality in the United States.It impacts people of all ages and demographics,particularly younger males and members of the military.Vision loss is commonly associated with traumatic brain injuries of all severities and can leave patients permanently disabled.This vision loss can be caused by injury to the visual system at multiple levels,including the eyes,optic nerves,and many different sites in the brain and brainstem(Sen,2017).Despite the far-reaching effects of visual impairment after traumatic brain injury,its incidence after traumatic brain injury is not well measured,and few successful treatments have been identified or implemented.
文摘Use of extracorporeal membrane oxygenation to support patients with critical cardiorespiratory illness is increasing.Systemic anticoagulation is an essential element in the care of extracorporeal membrane oxygenation patients.While unfractionated heparin is the most commonly used agent,unfractionated heparin is associated with several unique complications that can be catastrophic in critically ill patients,including heparin-induced thrombocytopenia and acquired antithrombin deficiency.These complications can result in thrombotic events and subtherapeutic anticoagulation.Direct thrombin inhibitors(DTIs)are emerging as alternative anticoagulants in patients supported by extracorporeal membrane oxygenation.Increasing evidence supports DTIs use as safe and effective in extracorporeal membrane oxygenation patients with and without heparininduced thrombocytopenia.This review outlines the pharmacology,dosing strategies and available protocols,monitoring parameters,and special use considerations for all available DTIs in extracorporeal membrane oxygenation patients.The advantages and disadvantages of DTIs in extracorporeal membrane oxygenation relative to unfractionated heparin will be described.
文摘Lesions of the rotator cuff(RC) are a common occurrence affecting millions of people across all parts of the globe. RC tears are also rampantly prevalent with an agedependent increase in numbers. Other associated factors include a history of trauma, limb dominance, contralateral shoulder, smoking-status, hypercholesterolemia, posture and occupational dispositions. The challenge lies in early diagnosis since a high proportion of patients are asymptomatic. Pain and decreasing shoulder power and function should alert the heedful practitioner in recognizing promptly the onset or aggravation of existing RC tears. Partial-thickness tears(PTT) can be bursalsided or articular-sided tears. Over the course of time, PTT enlarge and propagate into full-thickness tears(FTT) and develop distinct chronic pathological changes due to muscle retraction, fatty infiltration and muscle atrophy. These lead to a reduction in tendon elasticity and viability. Eventually, the glenohumeral joint experiences a series of degenerative alterations- cuff tear arthropathy. To avert this, a vigilant clinician must utilize and corroborate clinical skill and radiological findings to identify tear progression. Modern radio-diagnostic means of ultrasonography and magnetic resonance imaging provide excellent visualization of structural details and are crucial in determining further course of action for these patients. Physical therapy along with activity modifications, antiinflammatory and analgesic medications form the pillars of nonoperative treatment. Elderly patients with minimal functional demands can be managed conservatively and reassessed at frequent intervals. Regular monitoring helps in isolating patients who require surgical interventions. Early surgery should be considered in younger, active and symptomatic, healthy patients. In addition to being costeffective, this helps in providing a functional shoulder witha stable cuff. An easily reproducible technique of maximal strength and sturdiness should by chosen among the armamentarium of the
基金the NLRP3 inflammasome in the He laboratory was funded by NIH grant K22AI120988Wayne State University Startup
文摘Neurodegenerative diseases are a group of neuronal disorders caused by progressive neuronal cell death in different regions of the human brain.Alzheimer's disease(AD)and Parkinson's disease(PD)are the most common types of neurodegenerative diseases that affect millions of people worldwide.There is no cure available for either disease.One of the pathological hallmarks of neurodegenerative diseases is the abnormal protein aggregation in the central nervous system.
文摘The electrochemical basis for understanding the interaction of thiol collectors with sulfide minerals is reviewed. Spectroscopic techniques are being increasingly applied to augment electrochemical studies and provide unequivocal identification of species formed at mineral surfaces in flotation systems. These include X ray photoelectron, Fourier transform infrared spectroscopy and, more recently, surface enhanced Raman scattering spectroscopy. The progress that has been made in the application of electrochemical measurement to monitor and control flotation plants is also considered.
