In this study,a straightforward one-step hydrothermal method was successfully utilized to synthesize the solid solution Na_(0.9)Mg_(0.45)Ti_(3.55)O_(8)-Na_(2)Ni_(2)Ti_(6)O_(16)(NNMTO-x),where x denotes the molar perce...In this study,a straightforward one-step hydrothermal method was successfully utilized to synthesize the solid solution Na_(0.9)Mg_(0.45)Ti_(3.55)O_(8)-Na_(2)Ni_(2)Ti_(6)O_(16)(NNMTO-x),where x denotes the molar percentage of Na_(2)Ni_(2)Ti_(6)O_(16)(NNTO)within Na_(0.9)Mg_(0.45)Ti_(3.55)O_(8)(NMTO),with x values of 10,20,30,40,and 50.Both XPS(X-ray Photoelectron Spectroscopy)and EDX(Energy Dispersive X-ray Spectroscopy)analyses unequivocally validated the formation of the NNMTO-x solid solutions.It was observed that when x is below 40,the NNMTO-x solid solution retains the structural characteristics of the original NMTO.However,beyond this threshold,significant alterations in crystal morphology were noted,accompanied by a noticeable decline in photocatalytic activity.Notably,the absorption edge of NNMTO-x(x<40)exhibited a shift towards the visible-light spectrum,thereby substantially broadening the absorption range.The findings highlight that NNMTO-30 possesses the most pronounced photocatalytic activity for the reduction of CO_(2).Specifically,after a 6 h irradiation period,the production rates of CO and CH_(4)were recorded at 42.38 and 1.47μmol/g,respectively.This investigation provides pivotal insights that are instrumental in the advancement of highly efficient and stable photocatalysts tailored for CO_(2)reduction processes.展开更多
BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probi...BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.展开更多
I come from Slovenia,a small but ambitious country from Central Europe.I study at the Faculty of Electrical Engineering at the University of Ljublgana.I have the privilege of being one of the first young ambassadors o...I come from Slovenia,a small but ambitious country from Central Europe.I study at the Faculty of Electrical Engineering at the University of Ljublgana.I have the privilege of being one of the first young ambassadors of standardization not only in Slovenia but of this generation across the entire world.展开更多
Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemot...Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.展开更多
BACKGROUND Sorafenib has been the conventional treatment for advanced hepatocellular carcinoma(HCC)since 2008.While radiological complete responses are extremely rare,improved supportive care and multidisciplinary app...BACKGROUND Sorafenib has been the conventional treatment for advanced hepatocellular carcinoma(HCC)since 2008.While radiological complete responses are extremely rare,improved supportive care and multidisciplinary approaches in clinical practice may explain the recent increase in case reports and retrospective series documenting such responses.CASE SUMMARY This case series describes 3 patients with advanced HCC who achieved durable complete responses using first-line sorafenib therapy,even in the presence of portal vein thrombosis or extrahepatic spread,and highlights the potential for sustained remission in selected patients.Dermatologic toxicity and non-viral etiology may correlate with favorable outcomes;however,reliable predictive biomarkers for sorafenib response are lacking.CONCLUSION Future research into the etiology and molecular differences in HCC is necessary to develop more personalized therapy options.展开更多
Introduction:The choice is no longer whether—but when and how!Today,organizations can no longer choose whether or not to engage with stakeholders;the only real decision is when and how to do it successfully.Engaging ...Introduction:The choice is no longer whether—but when and how!Today,organizations can no longer choose whether or not to engage with stakeholders;the only real decision is when and how to do it successfully.Engaging stakeholders is essential for any type of organization,public,private,or civil society.In fact,it is a fundamental part of effective governance,continuous improvement,and social responsibility.The principle behind stakeholder engagement is simple yet powerful:those who can influence or be affected by an organization's mission must be given the opportunity to express their views and contribute to shaping the decisions that impact them.展开更多
Vacancy defects,as fundamental disruptions in metallic lattices,play an important role in shaping the mechanical and electronic properties of aluminum crystals.However,the influence of vacancy position under coupled t...Vacancy defects,as fundamental disruptions in metallic lattices,play an important role in shaping the mechanical and electronic properties of aluminum crystals.However,the influence of vacancy position under coupled thermomechanical fields remains insufficiently understood.In this study,transmission and scanning electron microscopy were employed to observe dislocation structures and grain boundary heterogeneities in processed aluminum alloys,suggesting stress concentrations and microstructural inhomogeneities associated with vacancy accumulation.To complement these observations,first-principles calculations and molecular dynamics simulations were conducted for seven single-vacancy configurations in face-centered cubic aluminum.The stress response,total energy,density of states(DOS),and differential charge density were examined under varying compressive strain(ε=0–0.1)and temperature(0–600 K).The results indicate that face-centered vacancies tend to reduce mechanical strength and perturb electronic states near the Fermi level,whereas corner and edge vacancies appear to have weaker effects.Elevated temperatures may partially restore electronic uniformity through thermal excitation.Overall,these findings suggest that vacancy position exerts a critical but position-dependent influence on coupled structure-property relationships,offering theoretical insights and preliminary experimental support for defect-engineered aluminum alloy design.展开更多
In this study,based on MERRA-2 reanalysis data and a multi-algorithm integrated atmospheric river(AR)iden-tification method,the authors reveal the cross-seasonal regulation mechanism of El Niño-Southern Oscillati...In this study,based on MERRA-2 reanalysis data and a multi-algorithm integrated atmospheric river(AR)iden-tification method,the authors reveal the cross-seasonal regulation mechanism of El Niño-Southern Oscillation(ENSO)on winter-spring AR activities in East Asia.The results show that ENSO asymmetrically modulates AR ac-tivity through teleconnection and hysteresis effects,and has significant enhancement/inhibition effects on ARs in different regions.At the onset of El Niño,enhanced southwesterly flow at the western edge of the western Pacific subtropical high(WPSH)leads to enhanced AR activity in the western Pacific,and anomalous southerly winds in the Indian Ocean promote northward transport of water vapor in the Arabian Sea and Bay of Bengal.With a three-month lag,the weakening and eastward retreat of the WPSH weakens the low-latitude AR activity,but persistent southerly winds in the Bay of Bengal maintain the AR activity over Southwest China.The mid-to high-latitude AR response exhibits delayed dynamics,initially dominated by the synergistic effect of the southward deviation of the upper-air rapids and the low-level convergence(double-rapid-flow effect)and later modulated by the Pacific-North American teleconnection(PNA)-triggered East Asian ridge,which enhances the precipitation efficiency through prolonged frontal activity and enhanced cold-warm airmass convergence.Overall,El Niño promotes the development of low-and midlatitude AR activity in East Asia,while La Niña promotes(maritime continental)AR activity in the tropics.This study establishes the“ENSO teleconnection→circulation adjust-ment→East Asian AR response”chain,revealing a cross-seasonal lagged response mechanisms of East Asian AR activity,and provides a theoretical basis for winter and spring climate prediction and extreme precipitation forecasting.展开更多
Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen...Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen et al systematically evaluated six complete blood count-derived inflammatory indices:Neutrophil-tolymphocyte ratio,monocyte-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune-inflammation index,systemic inflammatory response index(SIRI),and aggregate index of systemic inflammation and demonstrated their positive associations with GU prevalence,identifying SIRI as the strongest predictor.This editorial contextualizes these findings within the broader literature,clarifies that these indices reflect systemic rather than GU-specific inflammation,highlights methodological strengths and major limitations,and proposes a conceptual clinical algorithm for integrating SIRI into GU risk assessment.Future multicenter studies incorporating Helicobacter pylori infection,non-steroidal antiinflammatory drug exposure,and prospective design are essential to validate and translate these findings into clinical practice.展开更多
Fig fruit firmness decreases rapidly during ripening and after harvest,resulting in poor storability and transportation loss,which severely restricts development of the fresh fig industry.APETALA2/ethylene-responsive ...Fig fruit firmness decreases rapidly during ripening and after harvest,resulting in poor storability and transportation loss,which severely restricts development of the fresh fig industry.APETALA2/ethylene-responsive factor(AP2/ERF)transcription factors are downstream components of the ethylene-signaling pathway that play crucial roles in quality formation during fruit ripening.In this study,Ficus carica(Fc)ERF12 was clustered in repressor subfamily VIII of ERFs through phylogenetic analysis,and further recruited by its two EAR motifs and expression pattern during fig ripening.DNA affinity purification sequencing analysis indicated that FcERF12 binds to the promoter or gene body regions of multiple ripening-related genes,including cell wall-modification genes FcPG,FcXTH and FcPME,and ethylene-biosynthesis genes FcACS and FcACO.Yeast two-hybrid assay demonstrated that FcERF12 interacts with TOPLESS(TPL)co-repressors FcTPL1,FcTPL4 and FcTPL5,and histone deacetylases FcHDA6 and FcHDA19;interaction with FcTPL4 and FcTPL5 relied on the C-terminal EAR motif.Overexpressing FcERF12 in tomato did not change fruit size or yield,but resulted in an 18.37%increment in fruit firmness and a 49.62%reduction in ethylene-release rate at fruit ripening,accompanied by a significant decrease in seed number per fruit.Transcriptomic analysis revealed downregulation of tomato cell wallmodification genes SlPL,SlEXP and SlPG,and ethylene-synthesis genes SlACO and SlACS.Metabolomic profiling identified 82 differentially accumulated flavonoid metabolites,61 of them showing significantly decreased contents.Taken together,our results exhibit the negative regulatory role of FcERF12 in fig ethylene-signal transduction,providing new information on precise control of fruit firmness and other quality traits at ripening.展开更多
Foliar uptake of airborne metal(loid)s plays a crucial role in metal(loid)accumulation in plant organs and is influ-enced by the size and emission sources of aerosols.Given the high enrichment of toxic metal(loid)s in...Foliar uptake of airborne metal(loid)s plays a crucial role in metal(loid)accumulation in plant organs and is influ-enced by the size and emission sources of aerosols.Given the high enrichment of toxic metal(loid)s in submicron-scale particulates(PM1),this study established a PM1 exposure system to examine airborne metal(loid)accu-mulation and foliar physiological responses in Oryza sativa L.The results showed that the concentrations of Cu,Zn,As,Pb,and Cd in the leaves and grains were influenced not only by the airborne metal(loid)levels but also by the specific nature of the PM1 particles.The quantitative model for PM1-associated Pb entry into leaf tissue indicated that foliar Pb accumulation was primarily driven by particle adhesion,followed by hydrophilic pene-tration and trans-stomatal liquid film migration,accounting for 87%–89%of the total accumulation.The strong hygroscopicity and high Pb activity of PM1 emitted from waste incineration(WI)increased the Pb absorption coefficient via the hydrophilic and liquid film migration pathway.In contrast,the high hydrophobicity of PM1 from coal burning(CB)led to greater retention of Pb on leaf surfaces.Both foliar reactive oxygen metabolism and photosynthesis indices were sensitive to air pollution.Foliar metal(loid)accumulation and airborne PM1 concentration accounted for the variance in physiological responses in rice leaves.Our results also indicated that Pb was the key element in PM1 emissions from both coal burning(CB)and waste incineration(WI)responsible for significant physiological changes in rice leaves.展开更多
Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process...Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.展开更多
In wind power transmission via modular multilevel converter based high voltage direct current(MMCHVDC)systems,under traditional control strategies,MMC-HVDCcannot provide inertia support to the receiving-end grid(REG)d...In wind power transmission via modular multilevel converter based high voltage direct current(MMCHVDC)systems,under traditional control strategies,MMC-HVDCcannot provide inertia support to the receiving-end grid(REG)during disturbances.Moreover,due to the frequency decoupling between the two ends of the MMCHVDC,the sending-end wind farm(SEWF)cannot obtain the frequency variation information of the REG to provide inertia response.Therefore,this paper proposes a novel coordinated source-network-storage inertia control strategy based on wind power transmission via MMC-HVDC system.First,the grid-side MMC station(GS-MMC)maps the frequency variations of the REG to direct current(DC)voltage variations through the frequency mapping control,and uses submodule capacitor energy to provide inertial power.Then,the wind farm-side MMC station(WF-MMC)restores the DC voltage variations to frequency variations through the frequency restoration control and power loss compensation,providing real-time frequency information for the wind farm.Finally,based on real-time frequency information,thewind farmutilizes the rotor kinetic energy and energy storage to provide fast and lasting power support through the wind-storage coordinated inertia control strategy.Meanwhile,when the wind turbines withdraw from the inertia response phase,the energy storage can increase the power output to compensate for the power deficit,preventing secondary frequency drops.Furthermore,this paper uses small-signal analysis to determine the appropriate values for the key parameters of the proposed control strategy.A simulation model of the wind power transmission via MMCHVDC system is built in MATLAB/Simulink environment to validate and evaluate the proposed method.The results show that the proposed coordinated control strategy can effectively improve the system inertia level and avoid the secondary frequency drop under the load sudden increase condition.展开更多
To achieve the goals of sustainable development of the energy system and the construction of a lowcarbon society,this study proposes a multi-energy storage collaborative optimization strategy for industrial park that ...To achieve the goals of sustainable development of the energy system and the construction of a lowcarbon society,this study proposes a multi-energy storage collaborative optimization strategy for industrial park that integrates the laddered carbon trading mechanism with demand response.Firstly,a dual dimensional DR model is constructed based on the characteristics of load elasticity.The alternativeDRenables flexible substitution of energy loads through complementary conversion of electricity/heat/cold multi-energy sources,while the price DR relies on timeof-use electricity price signals to guide load spatiotemporal migration;Secondly,the LCT mechanism is introduced to achieve optimal carbon emission costs through a tiered carbon quota allocation mechanism.On this basis,an optimization decision model is established with the core objective of maximizing the annual net profit of the park.The objective function takes into account energy sales revenue,generator unit costs,and investment and operation costs of multiple types of energy storage facilities.Themodel constraint system covers three key dimensions:dynamic operation constraints of power generation units,including unit output limits,ramping capability,and minimum start-stop time;the physical boundary of an electric/hot/cold multi-energy storage system involves energy storage capacity and charge/discharge efficiency;The multi-energy network coupling balance equation ensures that the energy conversion and transmission process satisfies the law of conservation of energy.Using CPLEX mathematical programming solver for simulation verification,construct an energy storage capacity configuration decision process that includes LCT-DR synergistic effect.The research results show that compared with the traditional single energy storage configuration mode,this strategy effectively enhances the economic feasibility and engineering practicality of industrial park operation by coordinating demand side resource scheduling and finely controlling carbon costs,while maintaining stable system operation.Its methodological framework provides a technical path that combines theoretical rigor and practical operability for the low-carbon transformation of regional integrated energy systems.展开更多
Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear....Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear.We measured HDGF levels in the aqueous humor and found that HDGF was increased in DR but decreased after anti-angiogenesis treatment.Using public single-cell RNA sequencing datasets,we found that elevated HDGF in DR was mainly produced by Müller cells and targeted microglia.Additionally,integrin beta 2(Itgb2),a target gene of HDGF that induces microglial activation,was significantly upregulated in DR.To verify these results,we performed enzyme-linked immunosorbent assays,quantitative reverse transcription-PCR,Western blotting,and fluorescence immunostaining in cultured Müller and microglial cells treated with HDGF or anti-HDGF,as well as in DR mice receiving intravitreal injections of HDGF or its antibody.Exogenous HDGF further promoted microglial activation,migration,and secretion of pro-inflammatory cytokines,while neutralization of HDGF suppressed these effects caused by high glucose.Furthermore,the HDGF receptor nucleolin was overexpressed in microglia under high glucose stimulation.Therefore,blocking HDGF from Müller cells in DR reduced the excessive inflammatory response in microglia,highlighting HDGF as a potential therapeutic target.展开更多
Background:With the rapid development of modern emerging technologies,the ethical dilemmas and social controversies triggered by scientific and technological activities have become increasingly prominent.How to guide ...Background:With the rapid development of modern emerging technologies,the ethical dilemmas and social controversies triggered by scientific and technological activities have become increasingly prominent.How to guide technology for good and prevent and control technological risks has become an important issue of global concern.Research on science and technology ethics is dedicated to integrating ethical theories into governance practices and constructing ethical models that adapt to the development of the times.Methods:This article systematically reviews the six core approaches of scientific and technological ethics thought,including technological autonomy and political philosophy criticism,responsibility ethics and intergenerational obligations,technological intermediation and the integration of life and the world,ethical principles and normative frameworks,participatory governance and ethical practice innovation,as well as domain-specific ethical norms,thereby constructing an ethical analysis framework applicable to medical technology risks.And cross-analysis was conducted by taking medical events such as gene editing and xenotransplantation as examples.Results:Research shows that a single ethical approach has limitations in addressing complex medical ethical challenges,while the six approaches are complementary and synergistic.By criticizing technological autonomy,establishing a responsibility ethics orientation,setting the bottom line of ethical principles,promoting participatory governance,formulating domain norms,and continuously reflecting on the intermediary nature of technology,a multi-level and dynamically adaptive governance system for scientific and technological ethics can be constructed.Conclusion:The key to addressing contemporary medical ethics challenges lies in the comprehensive application of science and technology ethics theories and the integration of ethical considerations throughout the entire process of scientific and technological research and development.In the future,a governance framework that adapts to the development of new technologies should be established to promote cross-cultural and cross-disciplinary ethical dialogue and public participation,ensuring that scientific and technological innovation always serves the dignity of human life and overall well-being.展开更多
Neuroinflammation,the inflammatory response of the central nervous system(CNS),is a common feature of many neurological disorders such as sepsis-associated encephalopathy(SAE),multiple sclerosis(MS),and Parkinson'...Neuroinflammation,the inflammatory response of the central nervous system(CNS),is a common feature of many neurological disorders such as sepsis-associated encephalopathy(SAE),multiple sclerosis(MS),and Parkinson's disease(PD).Prior studies identified cytokines(e.g.,tumor necrosis factor[TNF],interleukin[IL]-1,and IL-6)delivered by resident glial cells and brain-invading peripheral immune cells as the major contributor to neuroinflammation(Becher et al.,2017).In addition to pro-inflammatory cytokines,elevated levels of extracellular purine molecules such as adenosine triphosphate(ATP)and adenosine can be detected upon any pathological insults(e.g.,injury,ischemia,and hypoxia),contributing to the progression of neurological disorders(Borea et al.,2017).展开更多
Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immun...Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.展开更多
Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central com...Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.展开更多
The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multi...The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.展开更多
基金Supported by the Doctoral Research Start-up Project of Yuncheng University(YQ-2023067)Project of Shanxi Natural Science Foundation(202303021211189)+1 种基金Fund Program for the Scientific Activities of Selected Returned Overseas Professionals in Shanxi Provinces(20220036)Shanxi ProvinceIntelligent Optoelectronic Sensing Application Technology Innovation Center and Shanxi Province Optoelectronic Information Science and TechnologyLaboratory,Yuncheng University.
文摘In this study,a straightforward one-step hydrothermal method was successfully utilized to synthesize the solid solution Na_(0.9)Mg_(0.45)Ti_(3.55)O_(8)-Na_(2)Ni_(2)Ti_(6)O_(16)(NNMTO-x),where x denotes the molar percentage of Na_(2)Ni_(2)Ti_(6)O_(16)(NNTO)within Na_(0.9)Mg_(0.45)Ti_(3.55)O_(8)(NMTO),with x values of 10,20,30,40,and 50.Both XPS(X-ray Photoelectron Spectroscopy)and EDX(Energy Dispersive X-ray Spectroscopy)analyses unequivocally validated the formation of the NNMTO-x solid solutions.It was observed that when x is below 40,the NNMTO-x solid solution retains the structural characteristics of the original NMTO.However,beyond this threshold,significant alterations in crystal morphology were noted,accompanied by a noticeable decline in photocatalytic activity.Notably,the absorption edge of NNMTO-x(x<40)exhibited a shift towards the visible-light spectrum,thereby substantially broadening the absorption range.The findings highlight that NNMTO-30 possesses the most pronounced photocatalytic activity for the reduction of CO_(2).Specifically,after a 6 h irradiation period,the production rates of CO and CH_(4)were recorded at 42.38 and 1.47μmol/g,respectively.This investigation provides pivotal insights that are instrumental in the advancement of highly efficient and stable photocatalysts tailored for CO_(2)reduction processes.
文摘BACKGROUND:Breast hyperplasia is a common benign breast disease mainly caused by endocrine disorders,manifested as abnormal hyperplasia of breast tissue.In recent years,traditional Chinese medicine compounds and probiotics have shown good potential in regulating the endocrine system and improving the intestinal microecology,providing new ideas for the treatment of breast hyperplasia.OBJECTIVE:To explore the effects and mechanisms of traditional Chinese medicine compounds and fermented probiotic compounds on breast hyperplasia in mice,providing new theoretical and experimental bases for the clinical treatment and prevention of breast hyperplasia.METHODS:(1)Network pharmacology tools were used to predict the anti-breast-hyperplasia activity of Herba Gueldenstaedtiae(Euphorbia humifusa),as well as its potential targets and signaling pathways.The databases included:TCMSP,OMIM,GeneCards database,UniProt website,Venny2.1.0 website,Metascape,HERB website,and STRING database,all of which are open-access databases.Network pharmacology can predict and screen key information such as the targets corresponding to the active ingredients of traditional Chinese medicine,disease targets,and action pathways through network analysis and computer-system analysis.Therefore,it has been increasingly widely used in the research of traditional Chinese medicine.(2)A breast hyperplasia model was induced in mice by injecting estrogen and progesterone.Mice in the normal blank group were injected intraperitoneally with normal saline every day.Mice in the model group and drugadministration groups were injected intraperitoneally with estradiol benzoate injection at a concentration of 0.5 mg/kg every day for 25 days.From the 26th day,the injection of estradiol benzoate injection was stopped.Mice in the normal blank group were injected intramuscularly with normal saline every day,and mice in the model group and drug-administration groups were injected intramuscularly with progesterone injection at a concentration of 5 mg/kg for 5 days.After the model was established,each group was given drugs respectively.The normal blank group and the model group were gavaged with 0.2 mL/d of normal saline;the positive blank group(Xiaozheng Pill group)was gavaged with an aqueous solution of Xiaozheng Pill at 0.9 mg/g;the low-,medium-and high-dose groups of Compound Herba Gueldenstaedtiae were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively;the low-,medium-and high-dose groups of traditional Chinese medicine-bacteria fermentation were gavaged with an aqueous solution of the compound medicine at 0.75,1.5,and 3.0 mg/(g·d)respectively.The administration was continuous for 30 days.RESULTS AND CONCLUSION:(1)The results of network pharmacology research showed that the Compound Herba Gueldenstaedtiae(Euphorbia humifusa)contained 46 active ingredients,which were related to 1213 potential targets.After comparison with 588 known breast-hyperplasia targets,it was speculated that 50 of these targets might be related to the direct effect of the compound on breast hyperplasia.(2)After drug intervention,there was no significant change in the high-dose group of Compound Herba Gueldenstaedtiae compared with the normal blank group.The liver indicators of the other intervention groups all significantly decreased(P<0.05).(3)In terms of kidney and uterine indicators,the medium-dose group of Compound Herba Gueldenstaedtiae decreased significantly compared with the normal blank group(P<0.05).In terms of the uterine index,the model group increased significantly compared with the normal blank group(P<0.01).(4)After 1-month drug treatment,the number of lobules and acini in the breast tissue of the Xiaozheng Pill group,the low,medium,and high-dose group of Compound Herba Gueldenstaedtiae,the low,medium,and highdose groups of traditional Chinese medicine-bacteria fermentation decreased,and the duct openings narrowed.With the increase of drug dose,diffuse hyperplasia of breast tissue was significantly improved.(5)The ELISA results showed that compared with the model group,the estrogen level was lower in the medium-dose group of traditional Chinese medicine-bacteria fermentation after the intervention(P<0.05).In addition,the follicle-stimulating hormone level in the low-dose group of Compound Herba Gueldenstaedtiae was lower than that of the model group(P<0.05).(6)The intervention in the mouse model led to changes in the abundance of short chain fatty acids and intestinal flora in all groups.To conclude,the Compound Herba Gueldenstaedtiae and its probiotic fermentation products significantly improved mammary gland hyperplasia in mice by regulating hormone levels,improving the structure of the gut microbiota,and increasing the content of shortchain fatty acids,providing new ideas and potential sources of drugs for the treatment of breast hyperplasia.
文摘I come from Slovenia,a small but ambitious country from Central Europe.I study at the Faculty of Electrical Engineering at the University of Ljublgana.I have the privilege of being one of the first young ambassadors of standardization not only in Slovenia but of this generation across the entire world.
文摘Colorectal cancer remains one of the leading causes of morbidity and mortality worldwide.Despite notable advances in early detection and therapeutic strategies,the molecular mechanisms underlying tumor survival,chemotherapy resistance,and metastasis are not yet fully understood.MicroRNAs(miRNAs)have emerged as pivotal regulators of cancer development,as they modulate gene expression and orchestrate key signaling pathways.However,the epigenetic mechanisms that control miRNA expression and their downstream gene targets remain largely unclear.In this review,we highlight the critical role of the colorectal cancer microenvironment in influencing miRNA expression and discuss how this regulation contributes to tumorigenesis.A better understanding of these processes may lead to the identification of novel therapeutic targets and strategies to prevent recurrence.
文摘BACKGROUND Sorafenib has been the conventional treatment for advanced hepatocellular carcinoma(HCC)since 2008.While radiological complete responses are extremely rare,improved supportive care and multidisciplinary approaches in clinical practice may explain the recent increase in case reports and retrospective series documenting such responses.CASE SUMMARY This case series describes 3 patients with advanced HCC who achieved durable complete responses using first-line sorafenib therapy,even in the presence of portal vein thrombosis or extrahepatic spread,and highlights the potential for sustained remission in selected patients.Dermatologic toxicity and non-viral etiology may correlate with favorable outcomes;however,reliable predictive biomarkers for sorafenib response are lacking.CONCLUSION Future research into the etiology and molecular differences in HCC is necessary to develop more personalized therapy options.
文摘Introduction:The choice is no longer whether—but when and how!Today,organizations can no longer choose whether or not to engage with stakeholders;the only real decision is when and how to do it successfully.Engaging stakeholders is essential for any type of organization,public,private,or civil society.In fact,it is a fundamental part of effective governance,continuous improvement,and social responsibility.The principle behind stakeholder engagement is simple yet powerful:those who can influence or be affected by an organization's mission must be given the opportunity to express their views and contribute to shaping the decisions that impact them.
基金supported by the Research Project on Strengthening the Construction of an Important Ecological Security Barrier in Northern China by Higher Education Institutions in the Inner Mongolia Autonomous Region(STAQZX202313)the Inner Mongolia Autonomous Region Education Science‘14th Five-Year Plan’2024 Annual Research Project(NGJGH2024635).
文摘Vacancy defects,as fundamental disruptions in metallic lattices,play an important role in shaping the mechanical and electronic properties of aluminum crystals.However,the influence of vacancy position under coupled thermomechanical fields remains insufficiently understood.In this study,transmission and scanning electron microscopy were employed to observe dislocation structures and grain boundary heterogeneities in processed aluminum alloys,suggesting stress concentrations and microstructural inhomogeneities associated with vacancy accumulation.To complement these observations,first-principles calculations and molecular dynamics simulations were conducted for seven single-vacancy configurations in face-centered cubic aluminum.The stress response,total energy,density of states(DOS),and differential charge density were examined under varying compressive strain(ε=0–0.1)and temperature(0–600 K).The results indicate that face-centered vacancies tend to reduce mechanical strength and perturb electronic states near the Fermi level,whereas corner and edge vacancies appear to have weaker effects.Elevated temperatures may partially restore electronic uniformity through thermal excitation.Overall,these findings suggest that vacancy position exerts a critical but position-dependent influence on coupled structure-property relationships,offering theoretical insights and preliminary experimental support for defect-engineered aluminum alloy design.
基金supported by the National Natural Science Foundation of China[grant number 41830964]the Natural Science Foundation of Hunan Province[grant number 2023JJ40666]。
文摘In this study,based on MERRA-2 reanalysis data and a multi-algorithm integrated atmospheric river(AR)iden-tification method,the authors reveal the cross-seasonal regulation mechanism of El Niño-Southern Oscillation(ENSO)on winter-spring AR activities in East Asia.The results show that ENSO asymmetrically modulates AR ac-tivity through teleconnection and hysteresis effects,and has significant enhancement/inhibition effects on ARs in different regions.At the onset of El Niño,enhanced southwesterly flow at the western edge of the western Pacific subtropical high(WPSH)leads to enhanced AR activity in the western Pacific,and anomalous southerly winds in the Indian Ocean promote northward transport of water vapor in the Arabian Sea and Bay of Bengal.With a three-month lag,the weakening and eastward retreat of the WPSH weakens the low-latitude AR activity,but persistent southerly winds in the Bay of Bengal maintain the AR activity over Southwest China.The mid-to high-latitude AR response exhibits delayed dynamics,initially dominated by the synergistic effect of the southward deviation of the upper-air rapids and the low-level convergence(double-rapid-flow effect)and later modulated by the Pacific-North American teleconnection(PNA)-triggered East Asian ridge,which enhances the precipitation efficiency through prolonged frontal activity and enhanced cold-warm airmass convergence.Overall,El Niño promotes the development of low-and midlatitude AR activity in East Asia,while La Niña promotes(maritime continental)AR activity in the tropics.This study establishes the“ENSO teleconnection→circulation adjust-ment→East Asian AR response”chain,revealing a cross-seasonal lagged response mechanisms of East Asian AR activity,and provides a theoretical basis for winter and spring climate prediction and extreme precipitation forecasting.
基金Supported by the National Natural Science Foundation of China,No.82170406 and No.81970238.
文摘Gastric ulcer(GU)represents a clinically significant manifestation of peptic ulcer disease,driven by a complex interplay of microbial,environmental,and immuneinflammatory factors.A recent cross-sectional study by Shen et al systematically evaluated six complete blood count-derived inflammatory indices:Neutrophil-tolymphocyte ratio,monocyte-to-lymphocyte ratio,platelet-to-lymphocyte ratio,systemic immune-inflammation index,systemic inflammatory response index(SIRI),and aggregate index of systemic inflammation and demonstrated their positive associations with GU prevalence,identifying SIRI as the strongest predictor.This editorial contextualizes these findings within the broader literature,clarifies that these indices reflect systemic rather than GU-specific inflammation,highlights methodological strengths and major limitations,and proposes a conceptual clinical algorithm for integrating SIRI into GU risk assessment.Future multicenter studies incorporating Helicobacter pylori infection,non-steroidal antiinflammatory drug exposure,and prospective design are essential to validate and translate these findings into clinical practice.
基金supported by the key research project for fig development of Weiyuan County(Grant No.1002-69199007),China.
文摘Fig fruit firmness decreases rapidly during ripening and after harvest,resulting in poor storability and transportation loss,which severely restricts development of the fresh fig industry.APETALA2/ethylene-responsive factor(AP2/ERF)transcription factors are downstream components of the ethylene-signaling pathway that play crucial roles in quality formation during fruit ripening.In this study,Ficus carica(Fc)ERF12 was clustered in repressor subfamily VIII of ERFs through phylogenetic analysis,and further recruited by its two EAR motifs and expression pattern during fig ripening.DNA affinity purification sequencing analysis indicated that FcERF12 binds to the promoter or gene body regions of multiple ripening-related genes,including cell wall-modification genes FcPG,FcXTH and FcPME,and ethylene-biosynthesis genes FcACS and FcACO.Yeast two-hybrid assay demonstrated that FcERF12 interacts with TOPLESS(TPL)co-repressors FcTPL1,FcTPL4 and FcTPL5,and histone deacetylases FcHDA6 and FcHDA19;interaction with FcTPL4 and FcTPL5 relied on the C-terminal EAR motif.Overexpressing FcERF12 in tomato did not change fruit size or yield,but resulted in an 18.37%increment in fruit firmness and a 49.62%reduction in ethylene-release rate at fruit ripening,accompanied by a significant decrease in seed number per fruit.Transcriptomic analysis revealed downregulation of tomato cell wallmodification genes SlPL,SlEXP and SlPG,and ethylene-synthesis genes SlACO and SlACS.Metabolomic profiling identified 82 differentially accumulated flavonoid metabolites,61 of them showing significantly decreased contents.Taken together,our results exhibit the negative regulatory role of FcERF12 in fig ethylene-signal transduction,providing new information on precise control of fruit firmness and other quality traits at ripening.
基金supported by the National Natural Science Foundation of China(Nos.42077367 and 21677123).
文摘Foliar uptake of airborne metal(loid)s plays a crucial role in metal(loid)accumulation in plant organs and is influ-enced by the size and emission sources of aerosols.Given the high enrichment of toxic metal(loid)s in submicron-scale particulates(PM1),this study established a PM1 exposure system to examine airborne metal(loid)accu-mulation and foliar physiological responses in Oryza sativa L.The results showed that the concentrations of Cu,Zn,As,Pb,and Cd in the leaves and grains were influenced not only by the airborne metal(loid)levels but also by the specific nature of the PM1 particles.The quantitative model for PM1-associated Pb entry into leaf tissue indicated that foliar Pb accumulation was primarily driven by particle adhesion,followed by hydrophilic pene-tration and trans-stomatal liquid film migration,accounting for 87%–89%of the total accumulation.The strong hygroscopicity and high Pb activity of PM1 emitted from waste incineration(WI)increased the Pb absorption coefficient via the hydrophilic and liquid film migration pathway.In contrast,the high hydrophobicity of PM1 from coal burning(CB)led to greater retention of Pb on leaf surfaces.Both foliar reactive oxygen metabolism and photosynthesis indices were sensitive to air pollution.Foliar metal(loid)accumulation and airborne PM1 concentration accounted for the variance in physiological responses in rice leaves.Our results also indicated that Pb was the key element in PM1 emissions from both coal burning(CB)and waste incineration(WI)responsible for significant physiological changes in rice leaves.
基金supported by the National Natural Science Foundation of China,Nos.82171344(to ZY),82471313(to CKT)the Guangdong Basic and Applied Basic Research Foundation,China,Nos.2023B1515120035,2024A1515012035(to CKT)The Science and Technology Projects in Guangzhou Nos.2025A03J4169(to ZY)。
文摘Stroke-induced alterations in cerebral blood flow trigger neurovascular remodeling,as manifested by the blood-brain barrier dysfunction and subs equent neurovascular repair activities such as angiogenesis.This process involves neurovascular communication that facilitates the transport of mediators among cerebrovascular endothelial cells,pericytes,glial cells,and neurons,thereby transmitting signals from donor to recipient cells to elicit a collaborative response.
基金funded by State Grid Corporation of China Central Branch Technology Project(52140024000C).
文摘In wind power transmission via modular multilevel converter based high voltage direct current(MMCHVDC)systems,under traditional control strategies,MMC-HVDCcannot provide inertia support to the receiving-end grid(REG)during disturbances.Moreover,due to the frequency decoupling between the two ends of the MMCHVDC,the sending-end wind farm(SEWF)cannot obtain the frequency variation information of the REG to provide inertia response.Therefore,this paper proposes a novel coordinated source-network-storage inertia control strategy based on wind power transmission via MMC-HVDC system.First,the grid-side MMC station(GS-MMC)maps the frequency variations of the REG to direct current(DC)voltage variations through the frequency mapping control,and uses submodule capacitor energy to provide inertial power.Then,the wind farm-side MMC station(WF-MMC)restores the DC voltage variations to frequency variations through the frequency restoration control and power loss compensation,providing real-time frequency information for the wind farm.Finally,based on real-time frequency information,thewind farmutilizes the rotor kinetic energy and energy storage to provide fast and lasting power support through the wind-storage coordinated inertia control strategy.Meanwhile,when the wind turbines withdraw from the inertia response phase,the energy storage can increase the power output to compensate for the power deficit,preventing secondary frequency drops.Furthermore,this paper uses small-signal analysis to determine the appropriate values for the key parameters of the proposed control strategy.A simulation model of the wind power transmission via MMCHVDC system is built in MATLAB/Simulink environment to validate and evaluate the proposed method.The results show that the proposed coordinated control strategy can effectively improve the system inertia level and avoid the secondary frequency drop under the load sudden increase condition.
基金funded by Science and Technology Projects from State Grid Corporation of China,(Research on Adaptive Balance Optimization and Simulation Technology of Industrial community Energy System with High Proportion of Distributed Energy,No.:5100-202355752A-3-4-SY).
文摘To achieve the goals of sustainable development of the energy system and the construction of a lowcarbon society,this study proposes a multi-energy storage collaborative optimization strategy for industrial park that integrates the laddered carbon trading mechanism with demand response.Firstly,a dual dimensional DR model is constructed based on the characteristics of load elasticity.The alternativeDRenables flexible substitution of energy loads through complementary conversion of electricity/heat/cold multi-energy sources,while the price DR relies on timeof-use electricity price signals to guide load spatiotemporal migration;Secondly,the LCT mechanism is introduced to achieve optimal carbon emission costs through a tiered carbon quota allocation mechanism.On this basis,an optimization decision model is established with the core objective of maximizing the annual net profit of the park.The objective function takes into account energy sales revenue,generator unit costs,and investment and operation costs of multiple types of energy storage facilities.Themodel constraint system covers three key dimensions:dynamic operation constraints of power generation units,including unit output limits,ramping capability,and minimum start-stop time;the physical boundary of an electric/hot/cold multi-energy storage system involves energy storage capacity and charge/discharge efficiency;The multi-energy network coupling balance equation ensures that the energy conversion and transmission process satisfies the law of conservation of energy.Using CPLEX mathematical programming solver for simulation verification,construct an energy storage capacity configuration decision process that includes LCT-DR synergistic effect.The research results show that compared with the traditional single energy storage configuration mode,this strategy effectively enhances the economic feasibility and engineering practicality of industrial park operation by coordinating demand side resource scheduling and finely controlling carbon costs,while maintaining stable system operation.Its methodological framework provides a technical path that combines theoretical rigor and practical operability for the low-carbon transformation of regional integrated energy systems.
基金supported by National Natural Science Foundation of China(Grant No.81900873 to A.Q.)the Jiangsu Provincial Key Research and Development Programme-social development(Grant No.BE2023777 to W.Z.)+1 种基金the Key Medical Research Project of Jiangsu Commission of Health(Grant No.H2022185 to W.Z.)the Clinical Capacity Enhancement Project of Jiangsu Province Hospital(Grant No.JSPH-MB-2023-18 to W.Z.)。
文摘Diabetic retinopathy(DR),a common complication of diabetes,is characterized by retinal angiogenesis and inflammation.The role of hepatoma-derived growth factor(HDGF)in mediating inflammation during DR remains unclear.We measured HDGF levels in the aqueous humor and found that HDGF was increased in DR but decreased after anti-angiogenesis treatment.Using public single-cell RNA sequencing datasets,we found that elevated HDGF in DR was mainly produced by Müller cells and targeted microglia.Additionally,integrin beta 2(Itgb2),a target gene of HDGF that induces microglial activation,was significantly upregulated in DR.To verify these results,we performed enzyme-linked immunosorbent assays,quantitative reverse transcription-PCR,Western blotting,and fluorescence immunostaining in cultured Müller and microglial cells treated with HDGF or anti-HDGF,as well as in DR mice receiving intravitreal injections of HDGF or its antibody.Exogenous HDGF further promoted microglial activation,migration,and secretion of pro-inflammatory cytokines,while neutralization of HDGF suppressed these effects caused by high glucose.Furthermore,the HDGF receptor nucleolin was overexpressed in microglia under high glucose stimulation.Therefore,blocking HDGF from Müller cells in DR reduced the excessive inflammatory response in microglia,highlighting HDGF as a potential therapeutic target.
基金supported by the National Key Research and Development Program(Grant No.2024YFA0917200)the Projects of the Chinese Center for Disease Control and Prevention(Grant No.BB2110240093)World Medical History under the Education Innovation Plan of the University of Science and Technology of China(Grant No.2024YCHX07).
文摘Background:With the rapid development of modern emerging technologies,the ethical dilemmas and social controversies triggered by scientific and technological activities have become increasingly prominent.How to guide technology for good and prevent and control technological risks has become an important issue of global concern.Research on science and technology ethics is dedicated to integrating ethical theories into governance practices and constructing ethical models that adapt to the development of the times.Methods:This article systematically reviews the six core approaches of scientific and technological ethics thought,including technological autonomy and political philosophy criticism,responsibility ethics and intergenerational obligations,technological intermediation and the integration of life and the world,ethical principles and normative frameworks,participatory governance and ethical practice innovation,as well as domain-specific ethical norms,thereby constructing an ethical analysis framework applicable to medical technology risks.And cross-analysis was conducted by taking medical events such as gene editing and xenotransplantation as examples.Results:Research shows that a single ethical approach has limitations in addressing complex medical ethical challenges,while the six approaches are complementary and synergistic.By criticizing technological autonomy,establishing a responsibility ethics orientation,setting the bottom line of ethical principles,promoting participatory governance,formulating domain norms,and continuously reflecting on the intermediary nature of technology,a multi-level and dynamically adaptive governance system for scientific and technological ethics can be constructed.Conclusion:The key to addressing contemporary medical ethics challenges lies in the comprehensive application of science and technology ethics theories and the integration of ethical considerations throughout the entire process of scientific and technological research and development.In the future,a governance framework that adapts to the development of new technologies should be established to promote cross-cultural and cross-disciplinary ethical dialogue and public participation,ensuring that scientific and technological innovation always serves the dignity of human life and overall well-being.
基金supported by grants from the Deutsche Forschungsgemeinschaft(HU 2614/1-1(Project No.462650276))the Fritz Thyssen Foundation(10.21.1.021MN)the Medical faculty of the University of Saarland(HOMFOR2016,HOMFORexzellent2017,HOMFOR2024 Anschubfinanzierung)to WH。
文摘Neuroinflammation,the inflammatory response of the central nervous system(CNS),is a common feature of many neurological disorders such as sepsis-associated encephalopathy(SAE),multiple sclerosis(MS),and Parkinson's disease(PD).Prior studies identified cytokines(e.g.,tumor necrosis factor[TNF],interleukin[IL]-1,and IL-6)delivered by resident glial cells and brain-invading peripheral immune cells as the major contributor to neuroinflammation(Becher et al.,2017).In addition to pro-inflammatory cytokines,elevated levels of extracellular purine molecules such as adenosine triphosphate(ATP)and adenosine can be detected upon any pathological insults(e.g.,injury,ischemia,and hypoxia),contributing to the progression of neurological disorders(Borea et al.,2017).
基金supported by the National Natural Science Foundation of China(Nos.82573045,82460602,82560459)the Hainan Provincial Graduate Student Innovative Research Project(No.Qhys2024-440).
文摘Post-translational modifications(PTMs)regulate the occurrence and development of cancer,and lactylation modification is a new form of PTMs.Recent studies have found that lactic acid modification can regulate the immune tolerance of cancer cells.The classical theory holds that prostate apoptosis response-4(PAR-4)is a tumor suppressor protein.However,our recent research has found that PAR-4 has a biological function of promoting cancer in hepatocellular carcinoma(HCC),and our analysis shows that PAR-4 can be modified of lactic acid.These research evidences suggest that PAR-4 lactylation modification may drive immune tolerance in HCC.Therefore,inhibiting PAR-4 lactylation modification is very likely to increase the sensitivity of HCC to immunotherapy.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC)+6 种基金STI2030-Major Projects(2021ZD0202700,to HY)the National Natural Science Foundation of China(32241004,to HY)the Natural Science Foundation of Zhejiang Province of China(LR24C090001,to HY)Key R&D Program of Zhejiang Province(2024SSYS0017,to HY)CAMS Innovation Fund for Medical Sciences(2019-12M-5-057,to HY)Fundamental Research Funds for the Central Universities(226-2022-00193,to HY)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-01,to HY)。
文摘Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.
基金supported by the National Natural Science Foundational of China(Key Program),No.U24A20692(to CJZ)the National Natural Science Foundational of China,Nos.82101414(to MLJ),82371355(to CJZ)+4 种基金the National Natural Science Foundational of China for Excellent Young Scholars,No.82022019(to CJZ)Sichuan Special Fund for Distinguished Young Scholars,No.24NSFJQ0052(to CJZ)The Innovation and Entrepreneurial Team of Sichuan Tianfu Emei Program,No.CZ2024018(to CJZ)Funding for Distinguished Young Scholars of Sichuan Provincial People’s Hospital,No.30420230005(to CJZ)Funding for Distinguished Young Scholars of University of Electronic Science and Technology of China,No.A1098531023601381(to CJZ)。
文摘The interleukin-17 family is the key group of cytokines and displays a broad spectrum of biological functions,including regulating the inflammatory cascade in various autoimmune and inflammatory diseases,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,Guillain–Barre syndrome,acute disseminated encephalomyelitis,diabetes,inflammatory skin diseases,joint inflammation,and cancer.Although the function of the interleukin-17 family has attracted increasing research attention over many years,the expression,function,and regulation mechanisms of different interleukin-17 members are complicated and still only partially understood.Currently,the interleukin-17A pathway is considered a critical therapeutic target for numerous immune and chronic inflammatory diseases,with several monoclonal antibodies against interleukin-17A having been successfully used in clinical practice.Whether other interleukin-17 members have the potential to be targeted in other diseases is still debated.This review first summarizes the recent advancements in understanding the physicochemical properties,physiological functions,cellular origins,and downstream signaling pathways of different members and corresponding receptors of the interleukin-17 family.Subsequently,the function of interleukin-17 in various immune diseases is discussed,and the important role of interleukin-17 in the pathological process of immune diseases is demonstrated from multiple perspectives.Then,the current status of targeted interleukin-17 therapy is summarized,and the effectiveness and safety of targeted interleukin-17 therapy are analyzed.Finally,the clinical application prospects of targeting the interleukin-17 pathway are discussed.
