V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating ene...V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown.In this study,we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity(DIO)mice.Under normal chow diet feeding,overexpression of Raf1 in AgRP neurons led to obesity in mice characterized by increased body weight,fat mass,and impaired glucose tolerance.Conversely,Raf1 knockout in AgRP neurons protected against diet-induced obesity,reducing fat mass and improving glucose tolerance.Mechanistically,Raf1 activated the MAPK signaling pathway,culminating in the phosphorylation of cAMP response element-binding protein(CREB),which enhanced transcription of Agrp and Npy.Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis,highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance.Collectively,these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis,positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.展开更多
The Chinese Pharmacopoeia 2020 edition was reviewed and approved by the National Medical Products Administration and the National Health Commission of the People’s Republic of China in July 2020.The current edition w...The Chinese Pharmacopoeia 2020 edition was reviewed and approved by the National Medical Products Administration and the National Health Commission of the People’s Republic of China in July 2020.The current edition was officially implemented on December 30,2020.The general chapters of the Chinese Pharmacopoeia discuss the general testing methods and guidelines,which are the common requirements and basis for the implementation of drug standards in the Chinese Pharmacopoeia.Owing to adherence to the principles of scientificity,versatility,operability,and sustainable development,there is an improvement in the general chapters of the 2020 edition over those of the previous editions.Further,the application of advanced and mature analytical techniques has expanded,the development of testing methods for exogenous pollutants in traditional Chinese medicines has been strengthened,and technical requirements are now better harmonized with international standards.The updated edition provides technical and methodological support to ensure safety,effectiveness,and control of pharmaceuticals in China and will play an important and active role in encouraging the application of advanced technologies,improving the quality control of medicines,and strengthening the means of drug regulation in China.This review provides a comprehensive introduction of the main features of and changes to the general chapters in the Chinese Pharmacopoeia 2020 edition and aims to provide reference for its correct understanding and accurate implementation.展开更多
The increased global incidence of chronic metabolic diseases,a vital threat to human health and a burden on our healthcare systems,includes a series of clinical metabolic syndromes such as obesity,diabetes,hypertensio...The increased global incidence of chronic metabolic diseases,a vital threat to human health and a burden on our healthcare systems,includes a series of clinical metabolic syndromes such as obesity,diabetes,hypertension,and dyslipidemia.One of the well-known probiotic microorganisms,Lactiplantibacillus plantarum plays an important role in promoting human health,including inhibiting the occurrence and development of a variety of chronic metabolic diseases.The present study provides an overview of the preventive and therapeutic effects of L.plantarum on diabetes,obesity,non-alcoholic fatty liver disease,kidney stone disease,and cardiovascular diseases in animal models and human clinical trials.Ingesting L.plantarum demonstrated its ability to reduce inflammatory and oxidative stress levels by regulating the production of cytokines and short-chain fatty acids(SCFAs),the activity of antioxidant enzymes,and the balance of intestinal microbial communities to alleviate the symptoms of chronic metabolic diseases.Furthermore,updated applications and technologies of L.plantarum in food and biopharmaceutical industries are also discussed.Understanding the characteristics and functions of L.plantarum will guide the development of related probiotic products and explore the modulatory benefit of L.plantarum supplementations on the prevention and treatment of multiple chronic metabolic diseases.展开更多
Silicon has a large impact on the energy supply and economy in the modern world. In industry, high purity silicon is firstly prepared by carbothermic reduction of silica with the produced raw silicon being further ref...Silicon has a large impact on the energy supply and economy in the modern world. In industry, high purity silicon is firstly prepared by carbothermic reduction of silica with the produced raw silicon being further refined by a modified Siemens method. This process suffers from the disadvantages of high cost and contaminant release and emission. As an alternative, the molten salt electrolysis approach, particularly the FFC Cambridge Process(FFC: Fray-Farthing-Chen), could realize high purity silicon products with morphology-controllable nanostructures at low or mild temperatures(generally 650–900 ℃). In this article, we review the development, reaction mechanisms, and electrolysis conditions of silicon production by the FFC Cambridge Process. Applications of the silicon products from electrolysis in molten salts are also discussed in terms of energy applications, including using them as the photovoltaic element in solar cells and as the charge storage phase in the negative electrode(negatrode) of lithium ion batteries.展开更多
Stimulated Raman scattering(SRS)microscopy has the ability of noninvasive imaging of specific chemical bonds and been increasingly used in biomedicine in recent years.Two pulsed Gaussian beams are used in traditional ...Stimulated Raman scattering(SRS)microscopy has the ability of noninvasive imaging of specific chemical bonds and been increasingly used in biomedicine in recent years.Two pulsed Gaussian beams are used in traditional SRS microscopes,providing with high lateral and axial spatial resolution.Because of the tight focus of the Gaussian beam,such an SRS microscopy is difficult to be used for imaging deep targets in scattering tissues.The SRS microscopy based on Bessel beams can solve the imaging problem to a certain extent.Here,we establish a theoretical model to calculate the SRS signal excited by two Bessel beams by integrating the SRS signal generation theory with the fractal propagation method.The fractal model of refractive index turbulence is employed to generate the scattering tissues where the light transport is modeled by the beam propagation method.We model the scattering tissues containing chemicals,calculate the SRS signals stimulated by two Bessel beams,discuss the influence of the fractal model parameters on signal generation,and compare them with those generated by the Gaussian beams.The results show that,even though the modeling parameters have great influence on SRS signal generation,the Bessel beams-based SRS can generate signals in deeper scattering tissues.展开更多
Objective: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B(LDHB) has been detected in breast cancer but the function of LDHB remains unknown.Methods: Weste...Objective: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B(LDHB) has been detected in breast cancer but the function of LDHB remains unknown.Methods: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer(NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of LDHB in NK cell activation.Results: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some cancers.Conclusions: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regulating immune responses and its potential as a therapeutic target for breast cancer.展开更多
Adsorptive removal of heavy metal ions from wastewater is very important,and the key is the development of efficient sorbents.In this work,oxygenated alkynyl carbon materials(OACMs)were synthesized via mechanochemical...Adsorptive removal of heavy metal ions from wastewater is very important,and the key is the development of efficient sorbents.In this work,oxygenated alkynyl carbon materials(OACMs)were synthesized via mechanochemical reaction of CaC_(2) and a carbonate(CaCO_(3),Na2CO_(3),or NaHCO_(3))at ambient temperature.The resultant OACMs are micro mesoporous carbon nanomaterials with high specific area(>648 m2 g^(-1)),highly crosslinked texture,and rich alkynyl and oxygenated groups.The OACMs exhibit excellent Hg(Ⅱ)adsorption due to the soft acid-soft base interaction between alkynyl and Hg(Ⅱ),and OACM-3 derived from CaC_(2) and NaHCO_(3) has the saturated Hg(Ⅱ)adsorbance of 483.9 mg g^(-1)along with good selectivity and recyclability.The adsorption is mainly chemisorption following the Langmuir mode.OACM-3 also shows high adsorbance for other heavy metal ions,e.g.256.6 mg g^(-1)for Pb(II),232.4 mg g^(-1)for Zn(II),and 198.7 mg g^(-1)for Cu(II).This work expands the mechnochemical reaction of CaC_(2)with carbonates and possibly other oxyanionic salts,provides a new synthesis approach for functional alkynyl carbon materials with excellent adsorption performance for heavy metal ions,as well as a feasible approach for CO2 resource utilization.展开更多
Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress.Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis.Delivering drugs wi...Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress.Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis.Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved.Herein,we reported a nanotransdermal delivery system composed of all-trans retinoic acid(TRA),triphenylphosphine(TPP)-modified cerium oxide(CeO2)nanoparticles,flexible nanoliposomes and gels(TCeO_(2)-TRA-FNL-Gel).The results revealed that TCeO_(2)synthesized by the anti-micelle method,with a size of approximately 5 nm,possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species(ROS).TCeO_(2)-TRA-FNL prepared by the film dispersion method,with a size of approximately 70 nm,showed high drug encapsulation efficiency(>96%).TCeO_(2)-TRA-FNL-Gel further showed sustained drug release behaviors,great transdermal permeation ability,and greater skin retention than the free TRA.The results of in vitro EGF-induced and H2O2-induced models suggested that TCeO_(2)-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells.The results of in vivo imiquimod(IMQ)-induced model indicated that TCeO_(2)-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms.In summary,the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.展开更多
Coherent anti-Stokes Raman scattering(CA RS)microscopy can resolve the chemical compo-nents and distribution of living biological systems in a label-firee manner and is favored in several disciplines.Current CA RS mic...Coherent anti-Stokes Raman scattering(CA RS)microscopy can resolve the chemical compo-nents and distribution of living biological systems in a label-firee manner and is favored in several disciplines.Current CA RS microscopes typically use bulky,high-performance solid-state lasers,which are expensive and sensitive to environmental changes.With their relatively low cost and environmental sensitivity,supercontinum fiber(SF)lasers with a small footprint have found increasing use in biomedical applications.Upon these features,in this paper,we homebuilt a low-cost CARS microscope based on a SF laser module(scCA RS microscope).This SF laser module is specially customized by adding a time synchronized seed source channel to the SF laser to form a dual-channel output laser.The performance of the scCARS microscope is evaluated with dimethyl sulfoxide,whose results confirm a spatial resolution of better than 500nm and a detection sensitivity of millimolar concentrations.The dual-color imaging capability is further demonstrated by imaging different species of mixed microspheres.We finally explore the potential of our scCARS microscope by mapping lipid droplets in different cancer cells and corneal stromal lenses.展开更多
[Objectives] To study the polyphenol oxidase (PPO) activity and total phenol content of Docynia indica .[Methods] The tender branches and petioles of the medicinal and edible plant D. indica were used as experimental ...[Objectives] To study the polyphenol oxidase (PPO) activity and total phenol content of Docynia indica .[Methods] The tender branches and petioles of the medicinal and edible plant D. indica were used as experimental materials, and the annual changes of total phenol content and polyphenol oxidase (PPO) activity were analyzed.[Results] pH 7.0 was the optimum value of polyphenol oxidase activity in D. indica plants;the best substrate was catechol with the concentration of 0.15 mol/L;the optimum temperature was 25 ℃.[Conclusions] The total phenol content of D. indica plants was the lowest in April, May and September of each year. The polyphenol oxidase activity of D. indica plants at flowering and fruiting stage was significantly higher than that at pre-flowering stage.展开更多
Our previous research studies have shown that Veratrilla baillonii Franch,a food supplement used by ethnic minorities in Southwest China,has multiple pharmacological activities,such as detoxification,antiinflammatory,...Our previous research studies have shown that Veratrilla baillonii Franch,a food supplement used by ethnic minorities in Southwest China,has multiple pharmacological activities,such as detoxification,antiinflammatory,antioxidant,and anti-insulin resistance.However,the detailed signal pathways for its salutary effect on damages in multiple organs due to type 2 diabetes mellitus(T2DM)remains unclear.The current study is to evaluate the therapeutic effects of V.baillonii on T2DM rats and to explore the underlying mechanisms.The T2DM rat model was successfully established by a high-sugar and high-fat diet(HFD)combination with intraperitoneal injection of a small dose of streptozotocin(STZ,35 mg/kg).Biochemical analysis and histopatholgical examinations were conducted to evaluate the anti-diabetic potential of water extracts of V.baillonii(WVBF).The results showed that the WVBF treatment can improve hyperglycemia and insulin resistance,ameliorate the liver,kidney and pancreas injuries via decreasing inflammatory cytokines such as IL-6 and TNF-α,and oxidative damages.Further investigation suggested that WVBF modulates the signal transductions of the IRS1/PI3K/AKT/GLUT4 and AMPK pathways.These findings demonstrate potentials of WVBF in the treatment of T2DM and possible mechanisms for its hepatoprotective activities.展开更多
[Objectives]To study the culture of callus produced by the leaves of the ethnic medicine‘E Se’,the induction of adventitious buds and the regeneration system of tissue culture seedlings.[Methods]Multi-factor orthogo...[Objectives]To study the culture of callus produced by the leaves of the ethnic medicine‘E Se’,the induction of adventitious buds and the regeneration system of tissue culture seedlings.[Methods]Multi-factor orthogonal experiment was used to design and analyze.[Results]The best medium for callus induction was MS+2.0 mg/L 6-BA+0.1 mg/L 2,4-D.By comparing the effects of cytokinin 6-BA,KT and TDZ on induction of adventitious bud differentiation,it was found that the optimum medium for adventitious bud regeneration was MS+0.5 mg/L 6-BA+0.5 mg/L KT+0.15 mg/L IBA.Finally,adding 0.2 mg/L IBA(0.1 or 0.2 mg/L)to MS medium could effectively make regenerated seedlings produce roots,and the efficiency was more than 70%.[Conclusions]It laid a foundation for the large-scale cultivation of the seedlings of the ethnic medicine‘E Se’and the promotion of their artificial cultivation.展开更多
The investigation of adsorption and desorption properties of shale are important for estimating reserves and exploitation. The shale samples used in this paper were from the marine shale on Longmaxi shale in Sichuan a...The investigation of adsorption and desorption properties of shale are important for estimating reserves and exploitation. The shale samples used in this paper were from the marine shale on Longmaxi shale in Sichuan and Hubei province, China. A series of analyses, such as organic carbon content test, vitrinite reflectance test, rock pyrolysis, X-ray diffraction, and N2/CO2 adsorption were performed. Gravimetric method with magnetic suspension balance was used to conduct isothermal adsorption and desorption experiments. The Langmuir, Freundlich, Langmuir-Freundlich, D-R, semi-pore, and Tothequations were used to fit the isothermal adsorption and desorption curves. And adsorption potential theory was used to explain the adsorption and desorption process. According to the results, the shale samples have a high level of organic carbon content with the same organic matter type II1 and high degree of maturation. The volume of adsorption increases rapidly and slows down to stable with the pressure increasing. Desorption is the inverse process of adsorption and 10 MPa - 0.5 MPa is the main period of shale gas desorption. The fitting results show that three-parameter isotherm equations are better than the two-parameter ones. The adsorption temperature has a great influence on adsorption volume, little effect on potential energy. Adsorption potential varies under different TOC to affect adsorption properties. Moreover, a large adsorption potential means that the gas molecule is easy to adsorb but difficult to desorb.展开更多
Dark matter has been in the discussion of important theories for long time. As technology developed, more and more particles have been suggested to be the candidate of dark matter. This review will first discuss the o...Dark matter has been in the discussion of important theories for long time. As technology developed, more and more particles have been suggested to be the candidate of dark matter. This review will first discuss the observation evidence of the existence of dark matter in the aspect of cosmic microwave background, galaxy rotation curves, velocity dispersions and gravitational lensing. We then focus on some important collider researches, such as HL-LHC and CEPC about dark matter candidates: WIMPs. Finally, we extend the topic considering dark energy and inflation.展开更多
The ataxia telangiectasia–mutated and Rad3-related(ATR)kinase is a master regulator of DNA damage response and replication stress in humans.Targeting ATR is the focus of oncology drug pipelines with a number of poten...The ataxia telangiectasia–mutated and Rad3-related(ATR)kinase is a master regulator of DNA damage response and replication stress in humans.Targeting ATR is the focus of oncology drug pipelines with a number of potent,selective ATR inhibitors currently in clinical development.Here,we determined the cryo-EM structures of the human ATR-ATRIP complex in the presence of VE-822 and RP-3500,two ATR inhibitors currently in Phase II clinical trials,achieving an overall resolution of approximately 3Å.These structures yield a near-complete atomic model of the ATR-ATRIP complex,revealing subunit stoichiometry,intramolecular and intermolecular interactions,and critical regulatory sites including an insertion in the PIKK regulatory domain(PRD).Structural comparison provides insights into the modes of action and selectivity of ATR inhibitors.The divergent binding modes near the solvent side and in the rear pocket area of VE-822 and RP-3500,particularly their disparate binding orientations,lead to varying conformational changes in the active site.Surprisingly,one ATR-ATRIP complex binds four VE-822 molecules,with two in the ATR active site and two at the ATR-ATR dimer interface.The binding and selectivity of RP-3500 depend on two bound water molecules,which may be further enhanced by the substitution of these bound waters.Our study provides a structural framework for understanding ATR regulation and holds promise for assisting future efforts in rational drug design targeting ATR.展开更多
Background and Aims:Epidemiological data on bacterial infections in cirrhosis in China remain limited.Therefore,we aimed to conduct a multicenter study to investigate the characteristics and outcomes of patients with ...Background and Aims:Epidemiological data on bacterial infections in cirrhosis in China remain limited.Therefore,we aimed to conduct a multicenter study to investigate the characteristics and outcomes of patients with cirrhosis and bacterial infections in China.Methods:We retrospectively enrolled 1,438 hospitalized adult patients with cirrhosis and bacterial or fungal infections from 24 hospitals across China between January 2018 and September 2024.Data on demographics,clinical features,microbiology,treatment,and outcomes were collected.Results:A total of 1,783 infection episodes were recorded,including 1,668 first infections and 115 second infections.Most infections were community-acquired(86.6%).Pneumonia was the most common infection type(26.7%),followed by spontaneous bacterial peritonitis(19.5%)and spontaneous bacteremia(14.1%).Among 754 pathogens isolated from 620 patients,Klebsiella pneumoniae(20.1%)was nearly as common as Escherichia coli(21.7%).Multidrug-resistant(MDR)organisms accounted for 41.0%of(20.1%)was nearly as common as Escherichia coli(21.7%).Multidrug-resistant(MDR)organisms accounted for 41.0%of all isolates,with extended-spectrum p-lactamase-producing Escherichia coli being the most prevalent MDR strain(8.9%of patients).Adherence to empirical antibiotic treatment guidelines from the European Association for the Study of the Liver was significantly lower in this cohort compared to the global study(21.5%vs.61.2%,P<0.001),accompanied by a lower clinical resolution rate(63.5%vs.79.8%,P<0.001).Conclusions:The clinical and microbiological characteristics of bacterial infections in patients with cirrhosis in China differ substantially from those reported in other regions.These findings highlight the need for region-specific management and prevention strategies,particularly in light of the changing microbiological landscape,high MDR prevalence,and suboptimal antibiotic practices.展开更多
Short-chain fatty acids(SCFAs)have been increasingly evidenced to be important bioactive metabolites of the gut microbiota and transducers in controlling diverse psychiatric or neurological disorders via the microbiot...Short-chain fatty acids(SCFAs)have been increasingly evidenced to be important bioactive metabolites of the gut microbiota and transducers in controlling diverse psychiatric or neurological disorders via the microbiota-gut-brain axis.However,the precise mechanism by which brain SCFAs extert multiple beneficial effects is not completely understood.Our previous research has demonstrated that the acetyl-coenzyme A synthetase short-chain family member 2(ACSS2)is a novel target of the rapid and long-lasting antidepressant responses.Here,we show that micromolar SCFAs significantly augment both total cellular and nuclear ACSS2 to trigger tryptophan hydroxylase 2(TPH2)promoter histone acetylation and its transcription in SH-SY5Y cells.In chronic-restraint-stress-induced depression mice,neuronal ACSS2 knockdown by stereotaxic injection of adeno-associated virus in the hippocampus abolished SCFA-mediated improvements in depressive-like behaviors of mice,supporting that ACSS2 is required for SCFA-mediated antidepressant responses.Mechanistically,the peroxisome-proliferator-activated receptor gamma(PPARγ)is identified as a novel partner of ACSS2 to activate TPH2 transcription.Importantly,PPARγis also responsible for SCFA-mediated antidepressant-like effects via ACSS2-TPH2 axis.To further support brain SCFAs as a therapeutic target for antidepressant effects,d-mannose,which is a naturally present hexose,can significantly reverse the dysbiosis of gut microbiota in the chronic-restraint-stress-exposure mice and augment brain SCFAs to protect against the depressive-like behaviors via ACSS2-PPARγ-TPH2 axis.In summary,brain SCFAs can activate ACSS2-PPARγ-TPH2 axis to play the antidepressive-like effects,and d-mannose is suggested to be an inducer of brain SCFAs in resisting depression.展开更多
Aims:Acute-on-chronic liver failure(ACLF)frequently develops in patients with compensated liver disease.We aimed to characterize the epidemiological features and mortality rates of ACLF in this population and their ch...Aims:Acute-on-chronic liver failure(ACLF)frequently develops in patients with compensated liver disease.We aimed to characterize the epidemiological features and mortality rates of ACLF in this population and their changes over time.Methods:We performed a meta-analysis of cohort studies on patients with ACLF and compensated liver disease to evaluate pooled baseline characteristics and mortality rates.Literature searches were conducted using EMBASE,PubMed,and the Cochrane Library,covering the period from January 1,2012,to December 31,2023.Following Freeman-Tukey double arcsine transformation,pooled estimates of mortality rates and etiological distributions were derived using a random-effects model.Subgroup analyses were performed according to country and period(pre-and post-2014).Results:Twenty-four studies involving 4,398 patients were included.The mean age was 48.7 years and 80.4%(3017/3824)were men,after excluding one study based on veterans.The mean Model for End-Stage Liver Disease score was 24.0.Viral hepatitis(42.2%,2070/4398)and alcohol-related liver disease(ALD)(35.6%,1328/4283)were the major etiologies of underlying chronic liver disease.Flare-ups of viral hepatitis(24.6%,788/2263)and alcohol consumption(33.1%,675/2263)were the predominant acute precipitants.The etiologies of ACLF and types of acute precipitants showed significant regional variation.The pooled 28-day mortality rate among patients with ACLF was 38.6%(1200/3225,95%confidence interval[CI]31.5%-45.8%),and the 90-day mortality rate was 45.8%(1625/3565,95%CI 40.3%-51.4%).Temporal analyses demonstrated a decline in virus-related ACLF,from 42.4%(1012/1761)in the pre-2014 period to 28.2%(490/1169)post-2014,and an increase in ALD-related ACLF,from 31.7%(439/1761)to 48.2%(469/1169).Conclusion:The number of patients with ACLF and compensated liver disease remained high,with no improvement over time.The rising prevalence of ALD-related ACLF over the past decade underscores the need for effective therapies for ACLF and preventive strategies for patients with ALD who are at high risk for ACLF.展开更多
基金support from various sources,including the National Natural Science Foundation of China(Grant Nos.81570774,82070872,92049118,and 82370854)the Junior Thousand Talents Program of China,and the Nanjing Medical University Startup Fund(All awarded to J.L.)support provided by Jiangsu Province's Innovation Personal as well as Innovative and Entrepreneurial Team of Jiangsu Province(Grant No.JSSCTD2021)(All awarded to J.L.).
文摘V-raf-leukemia viral oncogene 1(RAF1),a serine/threonine protein kinase,is well established to play a crucial role in tumorigenesis and cell development.However,the specific role of hypothalamic RAF1 in regulating energy metabolism remains unknown.In this study,we found that the expression of RAF1 was significantly increased in hypothalamic AgRP neurons of diet-induced obesity(DIO)mice.Under normal chow diet feeding,overexpression of Raf1 in AgRP neurons led to obesity in mice characterized by increased body weight,fat mass,and impaired glucose tolerance.Conversely,Raf1 knockout in AgRP neurons protected against diet-induced obesity,reducing fat mass and improving glucose tolerance.Mechanistically,Raf1 activated the MAPK signaling pathway,culminating in the phosphorylation of cAMP response element-binding protein(CREB),which enhanced transcription of Agrp and Npy.Insulin stimulation further potentiated the RAF1-MEK1/2-ERK1/2-CREB axis,highlighting RAF1's role in integrating hormonal and nutritional signals to regulate energy balance.Collectively,these findings underscore the important role of RAF1 in AgRP neurons in maintaining energy homeostasis and obesity pathogenesis,positioning it and its downstream pathways as potential therapeutic targets for innovative strategies to combat obesity and related metabolic diseases.
基金financial support from the Chinese Pharmacopoeia Commission Drug Standard Promoting Funds and Comprehensive Reform of the Chinese Drug and Medical Device Review and Approval System Funds(2015e2020)。
文摘The Chinese Pharmacopoeia 2020 edition was reviewed and approved by the National Medical Products Administration and the National Health Commission of the People’s Republic of China in July 2020.The current edition was officially implemented on December 30,2020.The general chapters of the Chinese Pharmacopoeia discuss the general testing methods and guidelines,which are the common requirements and basis for the implementation of drug standards in the Chinese Pharmacopoeia.Owing to adherence to the principles of scientificity,versatility,operability,and sustainable development,there is an improvement in the general chapters of the 2020 edition over those of the previous editions.Further,the application of advanced and mature analytical techniques has expanded,the development of testing methods for exogenous pollutants in traditional Chinese medicines has been strengthened,and technical requirements are now better harmonized with international standards.The updated edition provides technical and methodological support to ensure safety,effectiveness,and control of pharmaceuticals in China and will play an important and active role in encouraging the application of advanced technologies,improving the quality control of medicines,and strengthening the means of drug regulation in China.This review provides a comprehensive introduction of the main features of and changes to the general chapters in the Chinese Pharmacopoeia 2020 edition and aims to provide reference for its correct understanding and accurate implementation.
基金supported by the National Key Research and Development Projects(2019YFE0103800)Sichuan Science and Technology Program(2021ZHFP0045,2021YFN0092)+2 种基金International Research and Development Program of Sichuan(2019YFH0113,2021YFH0060,2021YFH0072)Chinese Hungarian Bilateral Project(2018-2.1.14-TÉT-CN-2018-00011,Chinese No.8-4)Food Fermentation Technology Research Team of Luzhou Vocational and Technical College(2021YJTD02).
文摘The increased global incidence of chronic metabolic diseases,a vital threat to human health and a burden on our healthcare systems,includes a series of clinical metabolic syndromes such as obesity,diabetes,hypertension,and dyslipidemia.One of the well-known probiotic microorganisms,Lactiplantibacillus plantarum plays an important role in promoting human health,including inhibiting the occurrence and development of a variety of chronic metabolic diseases.The present study provides an overview of the preventive and therapeutic effects of L.plantarum on diabetes,obesity,non-alcoholic fatty liver disease,kidney stone disease,and cardiovascular diseases in animal models and human clinical trials.Ingesting L.plantarum demonstrated its ability to reduce inflammatory and oxidative stress levels by regulating the production of cytokines and short-chain fatty acids(SCFAs),the activity of antioxidant enzymes,and the balance of intestinal microbial communities to alleviate the symptoms of chronic metabolic diseases.Furthermore,updated applications and technologies of L.plantarum in food and biopharmaceutical industries are also discussed.Understanding the characteristics and functions of L.plantarum will guide the development of related probiotic products and explore the modulatory benefit of L.plantarum supplementations on the prevention and treatment of multiple chronic metabolic diseases.
基金supported by the National Natural Science Foundation of China (No.51602234)Ningbo Municipal Government (3315 Plan and 2014A35001-1)UK Engineering and Physical Science Research Council (EP/J000582/1, GR/R68078)。
文摘Silicon has a large impact on the energy supply and economy in the modern world. In industry, high purity silicon is firstly prepared by carbothermic reduction of silica with the produced raw silicon being further refined by a modified Siemens method. This process suffers from the disadvantages of high cost and contaminant release and emission. As an alternative, the molten salt electrolysis approach, particularly the FFC Cambridge Process(FFC: Fray-Farthing-Chen), could realize high purity silicon products with morphology-controllable nanostructures at low or mild temperatures(generally 650–900 ℃). In this article, we review the development, reaction mechanisms, and electrolysis conditions of silicon production by the FFC Cambridge Process. Applications of the silicon products from electrolysis in molten salts are also discussed in terms of energy applications, including using them as the photovoltaic element in solar cells and as the charge storage phase in the negative electrode(negatrode) of lithium ion batteries.
基金This work was supported in part by the National Key R&D Program of China under Grant No.2018YFC0910600the National Natural Science Foundation of China under Grant Nos.81871397,81627807,11727813,91859109+2 种基金the Shaanxi Science Fund for Distinguished Young Scholars under Grant No.2020JC-27the Shaanxi Young Top-notch Talent of"Special Support Program"the Best Funded Projects for the Scientific and Technological Activities for Excellent Overseas Researchers in Shaanxi Province(2017017)..
文摘Stimulated Raman scattering(SRS)microscopy has the ability of noninvasive imaging of specific chemical bonds and been increasingly used in biomedicine in recent years.Two pulsed Gaussian beams are used in traditional SRS microscopes,providing with high lateral and axial spatial resolution.Because of the tight focus of the Gaussian beam,such an SRS microscopy is difficult to be used for imaging deep targets in scattering tissues.The SRS microscopy based on Bessel beams can solve the imaging problem to a certain extent.Here,we establish a theoretical model to calculate the SRS signal excited by two Bessel beams by integrating the SRS signal generation theory with the fractal propagation method.The fractal model of refractive index turbulence is employed to generate the scattering tissues where the light transport is modeled by the beam propagation method.We model the scattering tissues containing chemicals,calculate the SRS signals stimulated by two Bessel beams,discuss the influence of the fractal model parameters on signal generation,and compare them with those generated by the Gaussian beams.The results show that,even though the modeling parameters have great influence on SRS signal generation,the Bessel beams-based SRS can generate signals in deeper scattering tissues.
基金supported by the Shenzhen Science and Technology Program (Grant no. JCYJ20230807090459001)the Joint Research Fund of the National Science Fund of China Science and Technology Development Fund of Macao SAR (No. 32161160303 for NSFC and No. 0010/2021/AFJ for FDCT)the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University (Grant no. ZNJC202330)。
文摘Objective: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B(LDHB) has been detected in breast cancer but the function of LDHB remains unknown.Methods: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer(NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of LDHB in NK cell activation.Results: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some cancers.Conclusions: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regulating immune responses and its potential as a therapeutic target for breast cancer.
基金supports from the National Natural Science Foundation of China(No.21776015)the University Scientific Research Project of Anhui Province(No.KJ2018A0065&KJ2020A0245).
文摘Adsorptive removal of heavy metal ions from wastewater is very important,and the key is the development of efficient sorbents.In this work,oxygenated alkynyl carbon materials(OACMs)were synthesized via mechanochemical reaction of CaC_(2) and a carbonate(CaCO_(3),Na2CO_(3),or NaHCO_(3))at ambient temperature.The resultant OACMs are micro mesoporous carbon nanomaterials with high specific area(>648 m2 g^(-1)),highly crosslinked texture,and rich alkynyl and oxygenated groups.The OACMs exhibit excellent Hg(Ⅱ)adsorption due to the soft acid-soft base interaction between alkynyl and Hg(Ⅱ),and OACM-3 derived from CaC_(2) and NaHCO_(3) has the saturated Hg(Ⅱ)adsorbance of 483.9 mg g^(-1)along with good selectivity and recyclability.The adsorption is mainly chemisorption following the Langmuir mode.OACM-3 also shows high adsorbance for other heavy metal ions,e.g.256.6 mg g^(-1)for Pb(II),232.4 mg g^(-1)for Zn(II),and 198.7 mg g^(-1)for Cu(II).This work expands the mechnochemical reaction of CaC_(2)with carbonates and possibly other oxyanionic salts,provides a new synthesis approach for functional alkynyl carbon materials with excellent adsorption performance for heavy metal ions,as well as a feasible approach for CO2 resource utilization.
基金supported by Zhejiang Provincial Natural Science Foundation of China under Grant No.LYY21H300001Zhejiang Medical and Health Science and Technology project under Grant No.2021KY906Hangzhou Medical Key Discipline Construction Project under Grant No.[2021]21–39
文摘Psoriasis is an inflammatory skin disease that is intricately linked to oxidative stress.Antioxidation and inhibition of abnormal proliferation of keratinocytes are pivotal strategies for psoriasis.Delivering drugs with these effects to the site of skin lesions is a challenge that needs to be solved.Herein,we reported a nanotransdermal delivery system composed of all-trans retinoic acid(TRA),triphenylphosphine(TPP)-modified cerium oxide(CeO2)nanoparticles,flexible nanoliposomes and gels(TCeO_(2)-TRA-FNL-Gel).The results revealed that TCeO_(2)synthesized by the anti-micelle method,with a size of approximately 5 nm,possessed excellent mitochondrial targeting ability and valence conversion capability related to scavenging reactive oxygen species(ROS).TCeO_(2)-TRA-FNL prepared by the film dispersion method,with a size of approximately 70 nm,showed high drug encapsulation efficiency(>96%).TCeO_(2)-TRA-FNL-Gel further showed sustained drug release behaviors,great transdermal permeation ability,and greater skin retention than the free TRA.The results of in vitro EGF-induced and H2O2-induced models suggested that TCeO_(2)-TRA-FNL effectively reduced the level of inflammation and alleviated oxidative stress in HaCat cells.The results of in vivo imiquimod(IMQ)-induced model indicated that TCeO_(2)-TRA-FNL-Gel could greatly alleviate the psoriasis symptoms.In summary,the transdermal drug delivery system designed in this study has shown excellent therapeutic effects on psoriasis and is prospective for the safe and accurate therapy of psoriasis.
基金This work was supported in part by the National Key R&D Program of China(2018YFC0910600)the National Natural Science Foundation of China(81871397)+4 种基金the National Young Talent Program,the Shaanxi Science Fund for Distinguished Young Scholars(2020JC-27)the Key Research and Development Program of Shaanxi(2021ZDLSF04-05)the Shaanxi Young Top-notch Talent Program,the Best Funded Projects for the Scientific and Technological Activities for Excellent Overseas Researchers in Shaanxi Province(2017017)the Fundamental Research Funds for Central Universities(QTZX2105)Xueli Chen would like to thank Dr.Chi Zhang at Purdue University for his help in building the CARS microscope.
文摘Coherent anti-Stokes Raman scattering(CA RS)microscopy can resolve the chemical compo-nents and distribution of living biological systems in a label-firee manner and is favored in several disciplines.Current CA RS microscopes typically use bulky,high-performance solid-state lasers,which are expensive and sensitive to environmental changes.With their relatively low cost and environmental sensitivity,supercontinum fiber(SF)lasers with a small footprint have found increasing use in biomedical applications.Upon these features,in this paper,we homebuilt a low-cost CARS microscope based on a SF laser module(scCA RS microscope).This SF laser module is specially customized by adding a time synchronized seed source channel to the SF laser to form a dual-channel output laser.The performance of the scCARS microscope is evaluated with dimethyl sulfoxide,whose results confirm a spatial resolution of better than 500nm and a detection sensitivity of millimolar concentrations.The dual-color imaging capability is further demonstrated by imaging different species of mixed microspheres.We finally explore the potential of our scCARS microscope by mapping lipid droplets in different cancer cells and corneal stromal lenses.
基金Supported by Science and Technology Program of Sichuan Province(2018NZ0091)Special Project of Sichuan Provincial Public-Interest Scientific Institution Basal Research FundOpen Fund for Key Laboratory of Coarse Cereal Processing,Ministry of Agriculture and Rural Affairs(2018CC12)
文摘[Objectives] To study the polyphenol oxidase (PPO) activity and total phenol content of Docynia indica .[Methods] The tender branches and petioles of the medicinal and edible plant D. indica were used as experimental materials, and the annual changes of total phenol content and polyphenol oxidase (PPO) activity were analyzed.[Results] pH 7.0 was the optimum value of polyphenol oxidase activity in D. indica plants;the best substrate was catechol with the concentration of 0.15 mol/L;the optimum temperature was 25 ℃.[Conclusions] The total phenol content of D. indica plants was the lowest in April, May and September of each year. The polyphenol oxidase activity of D. indica plants at flowering and fruiting stage was significantly higher than that at pre-flowering stage.
基金supported by grants from the National Natural Science Foundation of China (81873090)Support Innovation and Development of Enterprise Technology Projects in Hubei Province (2021BLB174)the modern transmission and innovation research team of Traditional Chinese Medicine,South Central Minzu University。
文摘Our previous research studies have shown that Veratrilla baillonii Franch,a food supplement used by ethnic minorities in Southwest China,has multiple pharmacological activities,such as detoxification,antiinflammatory,antioxidant,and anti-insulin resistance.However,the detailed signal pathways for its salutary effect on damages in multiple organs due to type 2 diabetes mellitus(T2DM)remains unclear.The current study is to evaluate the therapeutic effects of V.baillonii on T2DM rats and to explore the underlying mechanisms.The T2DM rat model was successfully established by a high-sugar and high-fat diet(HFD)combination with intraperitoneal injection of a small dose of streptozotocin(STZ,35 mg/kg).Biochemical analysis and histopatholgical examinations were conducted to evaluate the anti-diabetic potential of water extracts of V.baillonii(WVBF).The results showed that the WVBF treatment can improve hyperglycemia and insulin resistance,ameliorate the liver,kidney and pancreas injuries via decreasing inflammatory cytokines such as IL-6 and TNF-α,and oxidative damages.Further investigation suggested that WVBF modulates the signal transductions of the IRS1/PI3K/AKT/GLUT4 and AMPK pathways.These findings demonstrate potentials of WVBF in the treatment of T2DM and possible mechanisms for its hepatoprotective activities.
基金Supported by Science and Technology Program of Sichuan Province(2018NZ0091)Special Project of Sichuan Provincial Public-Interest Scientific Institution Basal Research Fund+1 种基金Open Fund for Key Laboratory of Coarse Cereal Processing,Ministry of Agriculture and Rural Affairs(2018CC12)Scientific Research Projects of Sichuan Province Traditional Chinese Medicine Administration(2018KF007)
文摘[Objectives]To study the culture of callus produced by the leaves of the ethnic medicine‘E Se’,the induction of adventitious buds and the regeneration system of tissue culture seedlings.[Methods]Multi-factor orthogonal experiment was used to design and analyze.[Results]The best medium for callus induction was MS+2.0 mg/L 6-BA+0.1 mg/L 2,4-D.By comparing the effects of cytokinin 6-BA,KT and TDZ on induction of adventitious bud differentiation,it was found that the optimum medium for adventitious bud regeneration was MS+0.5 mg/L 6-BA+0.5 mg/L KT+0.15 mg/L IBA.Finally,adding 0.2 mg/L IBA(0.1 or 0.2 mg/L)to MS medium could effectively make regenerated seedlings produce roots,and the efficiency was more than 70%.[Conclusions]It laid a foundation for the large-scale cultivation of the seedlings of the ethnic medicine‘E Se’and the promotion of their artificial cultivation.
文摘The investigation of adsorption and desorption properties of shale are important for estimating reserves and exploitation. The shale samples used in this paper were from the marine shale on Longmaxi shale in Sichuan and Hubei province, China. A series of analyses, such as organic carbon content test, vitrinite reflectance test, rock pyrolysis, X-ray diffraction, and N2/CO2 adsorption were performed. Gravimetric method with magnetic suspension balance was used to conduct isothermal adsorption and desorption experiments. The Langmuir, Freundlich, Langmuir-Freundlich, D-R, semi-pore, and Tothequations were used to fit the isothermal adsorption and desorption curves. And adsorption potential theory was used to explain the adsorption and desorption process. According to the results, the shale samples have a high level of organic carbon content with the same organic matter type II1 and high degree of maturation. The volume of adsorption increases rapidly and slows down to stable with the pressure increasing. Desorption is the inverse process of adsorption and 10 MPa - 0.5 MPa is the main period of shale gas desorption. The fitting results show that three-parameter isotherm equations are better than the two-parameter ones. The adsorption temperature has a great influence on adsorption volume, little effect on potential energy. Adsorption potential varies under different TOC to affect adsorption properties. Moreover, a large adsorption potential means that the gas molecule is easy to adsorb but difficult to desorb.
文摘Dark matter has been in the discussion of important theories for long time. As technology developed, more and more particles have been suggested to be the candidate of dark matter. This review will first discuss the observation evidence of the existence of dark matter in the aspect of cosmic microwave background, galaxy rotation curves, velocity dispersions and gravitational lensing. We then focus on some important collider researches, such as HL-LHC and CEPC about dark matter candidates: WIMPs. Finally, we extend the topic considering dark energy and inflation.
基金supported by the National Natural Science Foundation of China(32030057,32271255,and 31922035)Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYZD20220001)+1 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB37010000)the Fundamental Research Funds for the Central Universities(WK9100000032).
文摘The ataxia telangiectasia–mutated and Rad3-related(ATR)kinase is a master regulator of DNA damage response and replication stress in humans.Targeting ATR is the focus of oncology drug pipelines with a number of potent,selective ATR inhibitors currently in clinical development.Here,we determined the cryo-EM structures of the human ATR-ATRIP complex in the presence of VE-822 and RP-3500,two ATR inhibitors currently in Phase II clinical trials,achieving an overall resolution of approximately 3Å.These structures yield a near-complete atomic model of the ATR-ATRIP complex,revealing subunit stoichiometry,intramolecular and intermolecular interactions,and critical regulatory sites including an insertion in the PIKK regulatory domain(PRD).Structural comparison provides insights into the modes of action and selectivity of ATR inhibitors.The divergent binding modes near the solvent side and in the rear pocket area of VE-822 and RP-3500,particularly their disparate binding orientations,lead to varying conformational changes in the active site.Surprisingly,one ATR-ATRIP complex binds four VE-822 molecules,with two in the ATR active site and two at the ATR-ATR dimer interface.The binding and selectivity of RP-3500 depend on two bound water molecules,which may be further enhanced by the substitution of these bound waters.Our study provides a structural framework for understanding ATR regulation and holds promise for assisting future efforts in rational drug design targeting ATR.
基金supported by the National Key Research and Development Program of China(No.2022YFC2304500,No.2021YFC2301800)the National Natural Science Foundation of China(No.81870425)+1 种基金the Fundamental Research Funds for the Central Universities(2023QZJH50)the Medical and Health Research Project of Zhejiang Province(2022RC141).
文摘Background and Aims:Epidemiological data on bacterial infections in cirrhosis in China remain limited.Therefore,we aimed to conduct a multicenter study to investigate the characteristics and outcomes of patients with cirrhosis and bacterial infections in China.Methods:We retrospectively enrolled 1,438 hospitalized adult patients with cirrhosis and bacterial or fungal infections from 24 hospitals across China between January 2018 and September 2024.Data on demographics,clinical features,microbiology,treatment,and outcomes were collected.Results:A total of 1,783 infection episodes were recorded,including 1,668 first infections and 115 second infections.Most infections were community-acquired(86.6%).Pneumonia was the most common infection type(26.7%),followed by spontaneous bacterial peritonitis(19.5%)and spontaneous bacteremia(14.1%).Among 754 pathogens isolated from 620 patients,Klebsiella pneumoniae(20.1%)was nearly as common as Escherichia coli(21.7%).Multidrug-resistant(MDR)organisms accounted for 41.0%of(20.1%)was nearly as common as Escherichia coli(21.7%).Multidrug-resistant(MDR)organisms accounted for 41.0%of all isolates,with extended-spectrum p-lactamase-producing Escherichia coli being the most prevalent MDR strain(8.9%of patients).Adherence to empirical antibiotic treatment guidelines from the European Association for the Study of the Liver was significantly lower in this cohort compared to the global study(21.5%vs.61.2%,P<0.001),accompanied by a lower clinical resolution rate(63.5%vs.79.8%,P<0.001).Conclusions:The clinical and microbiological characteristics of bacterial infections in patients with cirrhosis in China differ substantially from those reported in other regions.These findings highlight the need for region-specific management and prevention strategies,particularly in light of the changing microbiological landscape,high MDR prevalence,and suboptimal antibiotic practices.
基金supported by the National Natural Science Foundation of China(82101606,82173105,81771775,81971471,and 32270800)Shandong Excellent Young Scientists Fund Program(Overseas)(2022HWYQ-028)Shandong Provincial Natural Science Foundation(ZR2022MC012).
文摘Short-chain fatty acids(SCFAs)have been increasingly evidenced to be important bioactive metabolites of the gut microbiota and transducers in controlling diverse psychiatric or neurological disorders via the microbiota-gut-brain axis.However,the precise mechanism by which brain SCFAs extert multiple beneficial effects is not completely understood.Our previous research has demonstrated that the acetyl-coenzyme A synthetase short-chain family member 2(ACSS2)is a novel target of the rapid and long-lasting antidepressant responses.Here,we show that micromolar SCFAs significantly augment both total cellular and nuclear ACSS2 to trigger tryptophan hydroxylase 2(TPH2)promoter histone acetylation and its transcription in SH-SY5Y cells.In chronic-restraint-stress-induced depression mice,neuronal ACSS2 knockdown by stereotaxic injection of adeno-associated virus in the hippocampus abolished SCFA-mediated improvements in depressive-like behaviors of mice,supporting that ACSS2 is required for SCFA-mediated antidepressant responses.Mechanistically,the peroxisome-proliferator-activated receptor gamma(PPARγ)is identified as a novel partner of ACSS2 to activate TPH2 transcription.Importantly,PPARγis also responsible for SCFA-mediated antidepressant-like effects via ACSS2-TPH2 axis.To further support brain SCFAs as a therapeutic target for antidepressant effects,d-mannose,which is a naturally present hexose,can significantly reverse the dysbiosis of gut microbiota in the chronic-restraint-stress-exposure mice and augment brain SCFAs to protect against the depressive-like behaviors via ACSS2-PPARγ-TPH2 axis.In summary,brain SCFAs can activate ACSS2-PPARγ-TPH2 axis to play the antidepressive-like effects,and d-mannose is suggested to be an inducer of brain SCFAs in resisting depression.
基金supported by the National Key Research and Development Program of China(No.2022YFC2304500,No.2021YFC2301800)the National Natural Science Foundation of China(No.81870425)+1 种基金the Fundamental Research Funds for the Central Universities(2023QZJH50)the Medical and Health Research Project of Zhejiang Province(2022RC141).
文摘Aims:Acute-on-chronic liver failure(ACLF)frequently develops in patients with compensated liver disease.We aimed to characterize the epidemiological features and mortality rates of ACLF in this population and their changes over time.Methods:We performed a meta-analysis of cohort studies on patients with ACLF and compensated liver disease to evaluate pooled baseline characteristics and mortality rates.Literature searches were conducted using EMBASE,PubMed,and the Cochrane Library,covering the period from January 1,2012,to December 31,2023.Following Freeman-Tukey double arcsine transformation,pooled estimates of mortality rates and etiological distributions were derived using a random-effects model.Subgroup analyses were performed according to country and period(pre-and post-2014).Results:Twenty-four studies involving 4,398 patients were included.The mean age was 48.7 years and 80.4%(3017/3824)were men,after excluding one study based on veterans.The mean Model for End-Stage Liver Disease score was 24.0.Viral hepatitis(42.2%,2070/4398)and alcohol-related liver disease(ALD)(35.6%,1328/4283)were the major etiologies of underlying chronic liver disease.Flare-ups of viral hepatitis(24.6%,788/2263)and alcohol consumption(33.1%,675/2263)were the predominant acute precipitants.The etiologies of ACLF and types of acute precipitants showed significant regional variation.The pooled 28-day mortality rate among patients with ACLF was 38.6%(1200/3225,95%confidence interval[CI]31.5%-45.8%),and the 90-day mortality rate was 45.8%(1625/3565,95%CI 40.3%-51.4%).Temporal analyses demonstrated a decline in virus-related ACLF,from 42.4%(1012/1761)in the pre-2014 period to 28.2%(490/1169)post-2014,and an increase in ALD-related ACLF,from 31.7%(439/1761)to 48.2%(469/1169).Conclusion:The number of patients with ACLF and compensated liver disease remained high,with no improvement over time.The rising prevalence of ALD-related ACLF over the past decade underscores the need for effective therapies for ACLF and preventive strategies for patients with ALD who are at high risk for ACLF.
