Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxid...Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.展开更多
Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functio...Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.展开更多
Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiqu...Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.展开更多
This editorial explores the transformative potential of artificial intelligence(AI)in identifying conflicts of interest(COIs)within academic and scientific research.By harnessing advanced data analysis,pattern recogni...This editorial explores the transformative potential of artificial intelligence(AI)in identifying conflicts of interest(COIs)within academic and scientific research.By harnessing advanced data analysis,pattern recognition,and natural language processing techniques,AI offers innovative solutions for enhancing transparency and integrity in research.This editorial discusses how AI can automatically detect COIs,integrate data from various sources,and streamline reporting processes,thereby maintaining the credibility of scientific findings.展开更多
Tumors,due to their diversity and heterogeneity,pose a significant threat to human health.Multidrug resistance is a prevalent and grave issue in clinical treatment,resulting in treatment failure and cancer recurrence....Tumors,due to their diversity and heterogeneity,pose a significant threat to human health.Multidrug resistance is a prevalent and grave issue in clinical treatment,resulting in treatment failure and cancer recurrence.This resistance renders conventional drug therapies ineffective,presenting a substantial challenge to human health and medical care.Exploring natural products as potential sources for anti-cancer drugs could lead to the development of innovative and efficacious cancer treatments.This article aims to investigate the health implications of natural products(such as paclitaxel,podophyllotoxin,homoharringtonine,camptothecin,and vinblastine)in the discovery of anti-cancer drugs while discussing the methods and progress made in researching novel anti-cancer drugs derived from natural products.The paper discusses the diversity,intricate structures,and target affinity of natural products along with their structural modification techniques,combination therapies utilization possibilities with prodrugs or nanoparticles.Additionally,considering the escalating multidrug resistance observed in tumors nowadays;certain natural products offer new insights and approaches for discovering effective anti-tumor drugs that are crucial for addressing global public health challenges.The challenges faced by natural products during drug development including issues related to bioavailability toxicity concerns as well as limited resources are examined thoroughly.Potential opportunities current issues along with future challenges are highlighted aiming at facilitating the clinical translation of original anti-cancer drugs using natural products.展开更多
Objective:To investigate the effects of Alpiniae oxyphyllae Fructus(AOF)on renal lipid deposition in diabetic kidney disease(DKD)and elucidate its molecular mechanisms.Methods:The mechanism of AOF in treating DKD was ...Objective:To investigate the effects of Alpiniae oxyphyllae Fructus(AOF)on renal lipid deposition in diabetic kidney disease(DKD)and elucidate its molecular mechanisms.Methods:The mechanism of AOF in treating DKD was explored by network pharmacological enrichment analysis,molecular docking,and molecular dynamics simulation.The effects of AOF on renal function and lipid deposition were assessed in a mouse model of DKD and high glucose-stressed HK-2 cells.Cell viability and lipid accumulation were detected by CCK8 and oil red O staining.The expressions of PPARαand fatty acid oxidation-related genes(ACOX1 and CPT1A)were detected by quantitative RT-PCR,Western blot,and immunofluorescence.Furthermore,PPARαknockdown was performed to examine the molecular mechanism of AOF in treating DKD.Results:Network pharmacological enrichment analysis,molecular docking,and molecular dynamics simulation showed that the active compounds in AOF targeted PPARαand thus transcriptionally regulated ACOX1 and CPT1A.AOF lowered blood glucose,improved dyslipidemia,and attenuated renal injury in DKD mice.AOF-containing serum accentuated high glucose-induced decrease in cell viability and ameliorated lipid accumulation.Additionally,it significantly upregulated the expression of PPARα,ACOX1,and CPT1A in both in vivo and in vitro experiments,which was reversed by PPARαknockdown.Conclusions:AOF may promote fatty acid oxidation via PPARαto ameliorate renal lipid deposition in DKD.展开更多
Nel Paleartico occidentale la specie è distribuita in modo frammentario nellepatti centromeridionali.Per l’Italia settentrionale (Padania) è abbondante come esti-vante e nidificante e scarsamente localizzat...Nel Paleartico occidentale la specie è distribuita in modo frammentario nellepatti centromeridionali.Per l’Italia settentrionale (Padania) è abbondante come esti-vante e nidificante e scarsamente localizzata come svernante,mentre per il restodel territorio nazionale è più scarsa e localizzata.Nel censimento del 1981 venivanostimate 17500 coppie nidificanti in Italia (FASOLA e ALIERI,1992),pari al 41% dellapopolazione europea.La Lombardia nel 1981 ha ospitato il 56% della popolazioneitaliana e nel 1983-87 sono state occupate 24 garzaie (BRICHETTI e FASOLA,1990).展开更多
L’Airone rosso è specie distribuita in modo frammentario nell’Europa centro-meridionale.In Italia è migratore regolare e localizzato come nidificante,con unapopolazione stimata in circa 650 copie.In Lombar...L’Airone rosso è specie distribuita in modo frammentario nell’Europa centro-meridionale.In Italia è migratore regolare e localizzato come nidificante,con unapopolazione stimata in circa 650 copie.In Lombardia,secondo i recenti risultati dell’Atlante (BRICHETTI e FASOLA 1990)èrisultato presente in 13 garzaie,con una popolazione annualmente fluttuante:171展开更多
A seguito di regolari osservazioni effettuate nella Riserva Naturale Torbiere delSebino nel corso delle stagioni riproduttive 1992-1993 abbiamo riconfermato la nidi-ficazione di interessanti specie che hanno colonizza...A seguito di regolari osservazioni effettuate nella Riserva Naturale Torbiere delSebino nel corso delle stagioni riproduttive 1992-1993 abbiamo riconfermato la nidi-ficazione di interessanti specie che hanno colonizzato la Riserva nel 1991.Questeulteriori nidificazioni confermano le notevoli potenzialità delle Torbiere per la nidifi-cazione degli uccelli acquatici.展开更多
Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds bas...Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.展开更多
Based on the methodology for petroleum systems and through the anatomy and geochemical study of typical helium-rich gas fields,the geological conditions,genesis mechanisms,and accumulation patterns of helium resources...Based on the methodology for petroleum systems and through the anatomy and geochemical study of typical helium-rich gas fields,the geological conditions,genesis mechanisms,and accumulation patterns of helium resources in natural gas are investigated.Helium differs greatly from other natural gas resources in generation,migration,and accumulation.Helium is generated due to the slow alpha decay of basement U-/Th-rich elements or released from the deep crust and mantle,and then migrates along the composite transport system to natural gas reservoirs,where it accumulates with a suitable carrier gas.Helium migration and transport are controlled by the transport system consisting of lithospheric faults,basement faults,sedimentary layer faults,and effective transport layers.Based on the analysis of the helium-gas-water phase equilibrium in underground fluids and the phase-potential coupling,three occurrence states,i.e.water-soluble phase,gas-soluble phase and free phase,in the process of helium migration and accumulation,and three migration modes of helium,i.e.mass flow,seepage,and diffusion,are proposed.The formation and enrichment of helium-rich gas reservoirs are controlled by three major factors,i.e.high-quality helium source,high-efficiency transport and suitable carrier,and conform to three accumulation mechanisms,i.e.exsolution and convergence,buoyancy-driven,and differential pressure displacement.The helium-rich gas reservoirs discovered follow the distribution rule and accumulation pattern of near helium source,adjacent to fault,low potential area,and high position".To explore and evaluate helium-rich areas,it is necessary to conduct concurrent/parallel exploration of natural gas.The comprehensive evaluation and selection of profitable helium-rich areas with the characteristics of"source-trap connected,low fluid potential and high position,and proper natural gas volume matched with helium’s"should focus on the coupling and matching of the helium"source,migration,and accumulation elements"with the natural gas"source,reservoir and caprock conditions",and favorable carrier gas trap areas in local low fluid potential and high positions.展开更多
Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinester...Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.展开更多
The stability of the microstructure and mechanical properties of the pre-hardened sheets during the pre-hardening forming(PHF)process directly determines the quality of the formed components.The microstructure stabili...The stability of the microstructure and mechanical properties of the pre-hardened sheets during the pre-hardening forming(PHF)process directly determines the quality of the formed components.The microstructure stability of the pre-hardened sheets was in-vestigated by differential scanning calorimetry(DSC),transmission electron microscopy(TEM),and small angle X-ray scattering(SAXS),while the mechanical properties and formability were analyzed through uniaxial tensile tests and formability tests.The results in-dicate that the mechanical properties of the pre-hardened alloys exhibited negligible changes after experiencing 1-month natural aging(NA).The deviations of ultimate tensile strength(UTS),yield strength(YS),and sheet formability(Erichsen value)are all less than 2%.Also,after different NA time(from 48 h to 1 month)is applied to alloys before pre-hardening treatment,the pre-hardened alloys possess stable microstructure and mechanical properties as well.Interestingly,with the extension of NA time before pre-hardening treatment from 48 h to 1 month,the contribution of NA to the pre-hardening treatment is limited.Only a yield strength increment of 20 MPa is achieved,with no loss in elongation.The limited enhancement is mainly attributed to the fact that only a limited number of clusters are transformed into Guinier-Preston(GP)zones at the early stage of pre-hardening treatment,and the formation ofθ''phase inhibits the nucleation and growth of GP zones as the precipitated phase evolves.展开更多
With the growth of deep drilling and the complexity of the well profile,the requirements for a more complete and efficient exploitation of productive formations increase,which increases the risk of various complicatio...With the growth of deep drilling and the complexity of the well profile,the requirements for a more complete and efficient exploitation of productive formations increase,which increases the risk of various complications.Currently,reagents based on modified natural polymers(which are naturally occurring compounds)and synthetic polymers(SPs)which are polymeric compounds created industrially,are widely used to prevent emerging complications in the drilling process.However,compared to modified natural polymers,SPs form a family of high-molecular-weight compounds that are fully synthesized by undergoing chemical polymerization reactions.SPs provide substantial flexibility in their design.Moreover,their size and chemical composition can be adjusted to provide properties for nearly all the functional objectives of drilling fluids.They can be classified based on chemical ingredients,type of reaction,and their responses to heating.However,some of SPs,due to their structural characteristics,have a high cost,a poor temperature and salt resistance in drilling fluids,and degradation begins when the temperature reaches 130℃.These drawbacks prevent SP use in some medium and deep wells.Thus,this review addresses the historical development,the characteristics,manufacturing methods,classification,and the applications of SPs in drilling fluids.The contributions of SPs as additives to drilling fluids to enhance rheology,filtrate generation,carrying of cuttings,fluid lubricity,and clay/shale stability are explained in detail.The mechanisms,impacts,and advances achieved when SPs are added to drilling fluids are also described.The typical challenges encountered by SPs when deployed in drilling fluids and their advantages and drawbacks are also discussed.Economic issues also impact the applications of SPs in drilling fluids.Consequently,the cost of the most relevant SPs,and the monomers used in their synthesis,are assessed.Environmental impacts of SPs when deployed in drilling fluids,and their manufacturing processes are identified,together with advances in SP-treatment methods aimed at reducing those impacts.Recommendations for required future research addressing SP property and performance gaps are provided.展开更多
Zeolite catalysts have found extensive applications in the synthesis of various fine chemicals.However,the micropores of zeolites impose diffusion limitations on bulky molecules,greatly reducing the catalytic efficien...Zeolite catalysts have found extensive applications in the synthesis of various fine chemicals.However,the micropores of zeolites impose diffusion limitations on bulky molecules,greatly reducing the catalytic efficiency.Herein,we explore an economic and environmentally friendly method for synthesizing hierarchical NaX zeolite that exhibits improved catalytic performance in the Knoevenagel condensation reaction for producing the useful fine chemical 2-cyano-3-phenylacrylate.The synthesis was achieved via a low-temperature activation of kaolinite and subsequent in-situ transformation strategy without any template or seed.Systematic characterizations reveal that the synthesized NaX zeolite has both intercrystalline and intra-crystalline mesopores,smaller crystal size,and larger external specific surface area compared to commercial NaX zeolite.Detailed mechanism investigations show that the inter-crystalline mesopores are generated by stacking smaller crystals formed from in-situ crystallization of the depolymerized kaolinite,and the intra-crystalline mesopores are inherited from the pores in the depolymerized kaolinite.This synthesis strategy provides an energy-saving and effective way to construct hierarchical zeolites,which may gain wide applications in fine chemical manufacturing.展开更多
Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk fac...Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.展开更多
Different from oil and gas production,hydrate reservoirs are shallow and unconsolidated,whose mechanical properties deteriorate with hydrate decomposition.Therefore,the formations will undergo significant subsidence d...Different from oil and gas production,hydrate reservoirs are shallow and unconsolidated,whose mechanical properties deteriorate with hydrate decomposition.Therefore,the formations will undergo significant subsidence during depressurization,which will destroy the original force state of the production well.However,existing research on the stability of oil and gas production wells assumes the formation to be stable,and lacks consideration of the force exerted on the hydrate production well by formation subsidence caused by hydrate decomposition during production.To fill this gap,this paper proposes an analytical method for the dynamic evolution of the stability of hydrate production well considering the effects of hydrate decomposition.Based on the mechanical model of the production well,the basis for stability analysis has been proposed.A multi-field coupling model of the force state of the production well considering the effect of hydrate decomposition and formation subsidence is established,and a solver is developed.The analytical approach is verified by its good agreement with the results from the numerical method.A case study found that the decomposition of hydrate will increase the pulling-down force and reduce the supporting force,which is the main reason for the stability deterioration.The higher the initial hydrate saturation,the larger the reservoir thickness,and the lower the production pressure,the worse the stability or even instability.This work can provide a theoretical reference for the stability maintaining of the production well.展开更多
The accurate prediction of the friction angle of clays is crucial for assessing slope stability in engineering applications.This study addresses the importance of estimating the friction angle and presents the develop...The accurate prediction of the friction angle of clays is crucial for assessing slope stability in engineering applications.This study addresses the importance of estimating the friction angle and presents the development of four soft computing models:YJ-FPA-MLPnet,YJ-CRO-MLPnet,YJ-ACOC-MLPnet,and YJCSA-MLPnet.First of all,the Yeo-Johnson(YJ)transformation technique was used to stabilize the variance of data and make it more suitable for parametric statistical models that assume normality and equal variances.This technique is expected to improve the accuracy of friction angle prediction models.The friction angle prediction models then utilized multi-layer perceptron neural networks(MLPnet)and metaheuristic optimization algorithms to further enhance performance,including flower pollination algorithm(FPA),coral reefs optimization(CRO),ant colony optimization continuous(ACOC),and cuckoo search algorithm(CSA).The prediction models without the YJ technique,i.e.FPA-MLPnet,CRO-MLPnet,ACOC-MLPnet,and CSA-MLPnet,were then compared to those with the YJ technique,i.e.YJ-FPA-MLPnet,YJ-CRO-MLPnet,YJ-ACOC-MLPnet,and YJ-CSA-MLPnet.Among these,the YJ-CRO-MLPnet model demonstrated superior reliability,achieving an accuracy of up to 83%in predicting the friction angle of clay in practical engineering scenarios.This improvement is significant,as it represents an increase from 1.3%to approximately 20%compared to the models that did not utilize the YJ transformation technique.展开更多
The pan-Arctic is confronted with air pollution transported from lower latitudes.Observations have shown that aerosols help increase plant photosynthesis through the diffuse radiation fertilization effects(DRFEs).Whil...The pan-Arctic is confronted with air pollution transported from lower latitudes.Observations have shown that aerosols help increase plant photosynthesis through the diffuse radiation fertilization effects(DRFEs).While such DRFEs have been explored at low to middle latitudes,the aerosol impacts on pan-Arctic ecosystems and the contributions by anthropogenic and natural emission sources remain less quantified.Here,we perform regional simulations at 0.2o×0.2ousing a well-validated vegetation model(Yale Interactive terrestrial Biosphere,YIBs)in combination with multi-source of observations to quantify the impacts of aerosol DRFEs on the net primary productivity(NPP)in the pan-Arctic during 2001-19.Results show that aerosol DRFEs increase pan-Arctic NPP by 2.19 Pg C(12.8%)yr^(-1)under clear-sky conditions,in which natural and anthropogenic sources contribute to 8.9% and 3.9%,respectively.Under all-sky conditions,such DRFEs are largely dampened by cloud to only 0.26 Pg C(1.24%)yr^(-1),with contributions of 0.65% by natural and 0.59% by anthropogenic species.Natural aerosols cause a positive NPP trend of 0.022% yr^(-1)following the increased fire activities in the pan-Arctic.In contrast,anthropogenic aerosols induce a negative trend of-0.01% yr^(-1)due to reduced emissions from the middle latitudes.Such trends in aerosol DRFEs show a turning point in the year of 2007 with more positive NPP trends by natural aerosols but negative NPP trends by anthropogenic aerosols thereafter.Though affected by modeling uncertainties,this study suggests a likely increasing impact of aerosols on terrestrial ecosystems in the pan-Arctic under global warming.展开更多
Tracing the contamination origins in water sources and identifying the impacts of natural and human processes are essential for ecological safety and public health.However,current analysis approaches are not ideal,as ...Tracing the contamination origins in water sources and identifying the impacts of natural and human processes are essential for ecological safety and public health.However,current analysis approaches are not ideal,as they tend to be laborious,time-consuming,or technically difficult.Disinfection byproducts(DBPs)are a family of well-known secondary pollutants formed by the reactions of chemical disinfectants with DBP precursors during water disinfection treatment.Since DBP precursors have various origins(e.g.,natural,domestic,industrial,and agricultural sources),and since the formation of DBPs from different precursors in the presence of specific disinfectants is distinctive,we argue that DBPs and DBP precursors can serve as alternative indicators to assess the contamination in water sources and identify pollution origins.After providing a retrospective of the origins of DBPs and DBP precursors,as well as the specific formation patterns of DBPs from different precursors,this article presents an overview of the impacts of various natural and anthropogenic factors on DBPs and DBP precursors in drinking water sources.In practice,the DBPs(i.e.,their concentration and speciation)originally present in source water and the DBP precursors determined using DBP formation potential tests—in which water samples are dosed with a stoichiometric excess of specific disinfectants in order to maximize DBP formation under certain reaction conditions—can be considered as alternative metrics.When jointly used with other water quality parameters(e.g.,dissolved organic carbon,dissolved organic nitrogen,fluorescence,and molecular weight distribution)and specific contaminants of emerging concern(e.g.,certain pharmaceuticals and personal care products),DBPs and DBP precursors in drinking water sources can provide a more comprehensive picture of water pollution for better managing water resources and ensuring human health.展开更多
基金supported by the National Natural Science Foundation of China,No.82071442 (to LS)a grant from the Jilin Provincial Department of Finance,No.JLSWSRCZX2021-004 (to LS)。
文摘Alzheimer's disease is an age-related neurodegenerative disorder with a complex and incompletely understood pathogenesis. Despite extensive research, a cure for Alzheimer's disease has not yet been found. Oxidative stress mediates excessive oxidative responses, and its involvement in Alzheimer's disease pathogenesis as a primary or secondary pathological event is widely accepted. As a member of the selenium-containing antioxidant enzyme family, glutathione peroxidase 4 reduces esterified phospholipid hydroperoxides to maintain cellular redox homeostasis. With the discovery of ferroptosis, the central role of glutathione peroxidase 4 in anti-lipid peroxidation in several diseases, including Alzheimer's disease, has received widespread attention. Increasing evidence suggests that glutathione peroxidase 4 expression is inhibited in the Alzheimer's disease brain, resulting in oxidative stress, inflammation, ferroptosis, and apoptosis, which are closely associated with pathological damage in Alzheimer's disease. Several therapeutic approaches, such as small molecule drugs, natural plant products, and non-pharmacological treatments, ameliorate pathological damage and cognitive function in Alzheimer's disease by promoting glutathione peroxidase 4 expression and enhancing glutathione peroxidase 4 activity. Therefore, glutathione peroxidase 4 upregulation may be a promising strategy for the treatment of Alzheimer's disease. This review provides an overview of the gene structure, biological functions, and regulatory mechanisms of glutathione peroxidase 4, a discussion on the important role of glutathione peroxidase 4 in pathological events closely related to Alzheimer's disease, and a summary of the advances in small-molecule drugs, natural plant products, and non-pharmacological therapies targeting glutathione peroxidase 4 for the treatment of Alzheimer's disease. Most prior studies on this subject used animal models, and relevant clinical studies are lacking. Future clinical trials are required to validate the therapeutic effects of strategies targeting glutathione peroxidase 4 in the treatment of Alzheimer's disease.
基金supported by a grant from the Progressive MS Alliance(BRAVE in MS)Le Grand Portage Fund。
文摘Mature oligodendrocytes form myelin sheaths that are crucial for the insulation of axons and efficient signal transmission in the central nervous system.Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons.Despite the recognition of potential heterogeneity in mature oligodendrocyte function,a comprehensive summary of mature oligodendrocyte diversity is lacking.We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes.Indeed,recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences.Furthermore,modern molecular investigations,employing techniques such as single cell/nucleus RNA sequencing,consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region.Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis,Alzheimer's disease,and psychiatric disorders.Nevertheless,caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations.Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity.Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species,sex,central nervous system region,age,and disease,hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.
基金supported by Project of the Health Shanghai Initiative Special Fund(Medical-Sports Integration,Creating a New Model of Exercise for Health),No.JKSHZX-2022-02(to SC).
文摘Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.
文摘This editorial explores the transformative potential of artificial intelligence(AI)in identifying conflicts of interest(COIs)within academic and scientific research.By harnessing advanced data analysis,pattern recognition,and natural language processing techniques,AI offers innovative solutions for enhancing transparency and integrity in research.This editorial discusses how AI can automatically detect COIs,integrate data from various sources,and streamline reporting processes,thereby maintaining the credibility of scientific findings.
基金supported by the National Natural Science Foundation of China(grant number 22309103)Natural Science Foundation of Shandong Province(grant numbers ZR2022MH162,ZR2022QE202)+1 种基金PhD Research Start-up Foundation of Qufu Normal University(grant numbers 614901,615201)the project of introduction and cultivation for young innovation talents in the colleges and universities of Shandong Province(grant number 614202).
文摘Tumors,due to their diversity and heterogeneity,pose a significant threat to human health.Multidrug resistance is a prevalent and grave issue in clinical treatment,resulting in treatment failure and cancer recurrence.This resistance renders conventional drug therapies ineffective,presenting a substantial challenge to human health and medical care.Exploring natural products as potential sources for anti-cancer drugs could lead to the development of innovative and efficacious cancer treatments.This article aims to investigate the health implications of natural products(such as paclitaxel,podophyllotoxin,homoharringtonine,camptothecin,and vinblastine)in the discovery of anti-cancer drugs while discussing the methods and progress made in researching novel anti-cancer drugs derived from natural products.The paper discusses the diversity,intricate structures,and target affinity of natural products along with their structural modification techniques,combination therapies utilization possibilities with prodrugs or nanoparticles.Additionally,considering the escalating multidrug resistance observed in tumors nowadays;certain natural products offer new insights and approaches for discovering effective anti-tumor drugs that are crucial for addressing global public health challenges.The challenges faced by natural products during drug development including issues related to bioavailability toxicity concerns as well as limited resources are examined thoroughly.Potential opportunities current issues along with future challenges are highlighted aiming at facilitating the clinical translation of original anti-cancer drugs using natural products.
基金This work was supported by the grants from National Natural Science Foundation of China(No.82174334)2022 Postgraduate Innovation Research Projects in Hainan Province(No.Qhys2022-273).
文摘Objective:To investigate the effects of Alpiniae oxyphyllae Fructus(AOF)on renal lipid deposition in diabetic kidney disease(DKD)and elucidate its molecular mechanisms.Methods:The mechanism of AOF in treating DKD was explored by network pharmacological enrichment analysis,molecular docking,and molecular dynamics simulation.The effects of AOF on renal function and lipid deposition were assessed in a mouse model of DKD and high glucose-stressed HK-2 cells.Cell viability and lipid accumulation were detected by CCK8 and oil red O staining.The expressions of PPARαand fatty acid oxidation-related genes(ACOX1 and CPT1A)were detected by quantitative RT-PCR,Western blot,and immunofluorescence.Furthermore,PPARαknockdown was performed to examine the molecular mechanism of AOF in treating DKD.Results:Network pharmacological enrichment analysis,molecular docking,and molecular dynamics simulation showed that the active compounds in AOF targeted PPARαand thus transcriptionally regulated ACOX1 and CPT1A.AOF lowered blood glucose,improved dyslipidemia,and attenuated renal injury in DKD mice.AOF-containing serum accentuated high glucose-induced decrease in cell viability and ameliorated lipid accumulation.Additionally,it significantly upregulated the expression of PPARα,ACOX1,and CPT1A in both in vivo and in vitro experiments,which was reversed by PPARαknockdown.Conclusions:AOF may promote fatty acid oxidation via PPARαto ameliorate renal lipid deposition in DKD.
文摘Nel Paleartico occidentale la specie è distribuita in modo frammentario nellepatti centromeridionali.Per l’Italia settentrionale (Padania) è abbondante come esti-vante e nidificante e scarsamente localizzata come svernante,mentre per il restodel territorio nazionale è più scarsa e localizzata.Nel censimento del 1981 venivanostimate 17500 coppie nidificanti in Italia (FASOLA e ALIERI,1992),pari al 41% dellapopolazione europea.La Lombardia nel 1981 ha ospitato il 56% della popolazioneitaliana e nel 1983-87 sono state occupate 24 garzaie (BRICHETTI e FASOLA,1990).
文摘L’Airone rosso è specie distribuita in modo frammentario nell’Europa centro-meridionale.In Italia è migratore regolare e localizzato come nidificante,con unapopolazione stimata in circa 650 copie.In Lombardia,secondo i recenti risultati dell’Atlante (BRICHETTI e FASOLA 1990)èrisultato presente in 13 garzaie,con una popolazione annualmente fluttuante:171
文摘A seguito di regolari osservazioni effettuate nella Riserva Naturale Torbiere delSebino nel corso delle stagioni riproduttive 1992-1993 abbiamo riconfermato la nidi-ficazione di interessanti specie che hanno colonizzato la Riserva nel 1991.Questeulteriori nidificazioni confermano le notevoli potenzialità delle Torbiere per la nidifi-cazione degli uccelli acquatici.
基金supported by the National Natural Science Foundation of China(52003113,31900950,82102334,82002313,82072444)the National Key Research&Development Program of China(2018YFC2001502,2018YFB1105705)+6 种基金the Guangdong Basic and Applied Basic Research Foundation(2021A1515010745,2020A1515110356,2023A1515011986)the Shenzhen Fundamental Research Program(JCYJ20190808120405672)the Key Program of the National Natural Science Foundation of Zhejiang Province(LZ22C100001)the Natural Science Foundation of Shanghai(20ZR1469800)the Integration Innovation Fund of Shanghai Jiao Tong University(2021JCPT03),the Science and Technology Projects of Guangzhou City(202102020359)the Zigong Key Science and Technology Plan(2022ZCNKY07).SXC thanks the financial support under the Startup Grant of the University of Chinese Academy of Sciences(WIUCASQD2021026).HW thanks the Futian Healthcare Research Project(FTWS2022013)the financial support of China Postdoctoral Science Foundation(2021TQ0118).SL thanks the financial support of China Postdoctoral Science Foundation(2022M721490).
文摘Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.
基金Supported by the CNPC Technology Research Project(2021ZG13)。
文摘Based on the methodology for petroleum systems and through the anatomy and geochemical study of typical helium-rich gas fields,the geological conditions,genesis mechanisms,and accumulation patterns of helium resources in natural gas are investigated.Helium differs greatly from other natural gas resources in generation,migration,and accumulation.Helium is generated due to the slow alpha decay of basement U-/Th-rich elements or released from the deep crust and mantle,and then migrates along the composite transport system to natural gas reservoirs,where it accumulates with a suitable carrier gas.Helium migration and transport are controlled by the transport system consisting of lithospheric faults,basement faults,sedimentary layer faults,and effective transport layers.Based on the analysis of the helium-gas-water phase equilibrium in underground fluids and the phase-potential coupling,three occurrence states,i.e.water-soluble phase,gas-soluble phase and free phase,in the process of helium migration and accumulation,and three migration modes of helium,i.e.mass flow,seepage,and diffusion,are proposed.The formation and enrichment of helium-rich gas reservoirs are controlled by three major factors,i.e.high-quality helium source,high-efficiency transport and suitable carrier,and conform to three accumulation mechanisms,i.e.exsolution and convergence,buoyancy-driven,and differential pressure displacement.The helium-rich gas reservoirs discovered follow the distribution rule and accumulation pattern of near helium source,adjacent to fault,low potential area,and high position".To explore and evaluate helium-rich areas,it is necessary to conduct concurrent/parallel exploration of natural gas.The comprehensive evaluation and selection of profitable helium-rich areas with the characteristics of"source-trap connected,low fluid potential and high position,and proper natural gas volume matched with helium’s"should focus on the coupling and matching of the helium"source,migration,and accumulation elements"with the natural gas"source,reservoir and caprock conditions",and favorable carrier gas trap areas in local low fluid potential and high positions.
文摘Alzheimer’s disease is a progressive neurodegenerative disorder and the most common cause of dementia that principally affects older adults.Pathogenic factors,such as oxidative stress,an increase in acetylcholinesterase activity,mitochondrial dysfunction,genotoxicity,and neuroinflammation are present in this syndrome,which leads to neurodegeneration.Neurodegenerative pathologies such as Alzheimer’s disease are considered late-onset diseases caused by the complex combination of genetic,epigenetic,and environmental factors.There are two main types of Alzheimer’s disease,known as familial Alzheimer’s disease(onset<65 years)and late-onset or sporadic Alzheimer’s disease(onset≥65 years).Patients with familial Alzheimer’s disease inherit the disease due to rare mutations on the amyloid precursor protein(APP),presenilin 1 and 2(PSEN1 and PSEN2)genes in an autosomaldominantly fashion with closely 100%penetrance.In contrast,a different picture seems to emerge for sporadic Alzheimer’s disease,which exhibits numerous non-Mendelian anomalies suggesting an epigenetic component in its etiology.Importantly,the fundamental pathophysiological mechanisms driving Alzheimer’s disease are interfaced with epigenetic dysregulation.However,the dynamic nature of epigenetics seems to open up new avenues and hope in regenerative neurogenesis to improve brain repair in Alzheimer’s disease or following injury or stroke in humans.In recent years,there has been an increase in interest in using natural products for the treatment of neurodegenerative illnesses such as Alzheimer’s disease.Through epigenetic mechanisms,such as DNA methylation,non-coding RNAs,histone modification,and chromatin conformation regulation,natural compounds appear to exert neuroprotective effects.While we do not purport to cover every in this work,we do attempt to illustrate how various phytochemical compounds regulate the epigenetic effects of a few Alzheimer’s disease-related genes.
基金supported by the National Natural Science Foundation of China (Nos.52075400 and 52275368)the 111 Project (No.B17034)+1 种基金the Key Research and Development Program of Hubei Province,China (Nos.2021BAA200 and 2022AAA001)the Independent Innovation Projects of the Hubei Longzhong Laboratory (No.2022ZZ-04)。
文摘The stability of the microstructure and mechanical properties of the pre-hardened sheets during the pre-hardening forming(PHF)process directly determines the quality of the formed components.The microstructure stability of the pre-hardened sheets was in-vestigated by differential scanning calorimetry(DSC),transmission electron microscopy(TEM),and small angle X-ray scattering(SAXS),while the mechanical properties and formability were analyzed through uniaxial tensile tests and formability tests.The results in-dicate that the mechanical properties of the pre-hardened alloys exhibited negligible changes after experiencing 1-month natural aging(NA).The deviations of ultimate tensile strength(UTS),yield strength(YS),and sheet formability(Erichsen value)are all less than 2%.Also,after different NA time(from 48 h to 1 month)is applied to alloys before pre-hardening treatment,the pre-hardened alloys possess stable microstructure and mechanical properties as well.Interestingly,with the extension of NA time before pre-hardening treatment from 48 h to 1 month,the contribution of NA to the pre-hardening treatment is limited.Only a yield strength increment of 20 MPa is achieved,with no loss in elongation.The limited enhancement is mainly attributed to the fact that only a limited number of clusters are transformed into Guinier-Preston(GP)zones at the early stage of pre-hardening treatment,and the formation ofθ''phase inhibits the nucleation and growth of GP zones as the precipitated phase evolves.
文摘With the growth of deep drilling and the complexity of the well profile,the requirements for a more complete and efficient exploitation of productive formations increase,which increases the risk of various complications.Currently,reagents based on modified natural polymers(which are naturally occurring compounds)and synthetic polymers(SPs)which are polymeric compounds created industrially,are widely used to prevent emerging complications in the drilling process.However,compared to modified natural polymers,SPs form a family of high-molecular-weight compounds that are fully synthesized by undergoing chemical polymerization reactions.SPs provide substantial flexibility in their design.Moreover,their size and chemical composition can be adjusted to provide properties for nearly all the functional objectives of drilling fluids.They can be classified based on chemical ingredients,type of reaction,and their responses to heating.However,some of SPs,due to their structural characteristics,have a high cost,a poor temperature and salt resistance in drilling fluids,and degradation begins when the temperature reaches 130℃.These drawbacks prevent SP use in some medium and deep wells.Thus,this review addresses the historical development,the characteristics,manufacturing methods,classification,and the applications of SPs in drilling fluids.The contributions of SPs as additives to drilling fluids to enhance rheology,filtrate generation,carrying of cuttings,fluid lubricity,and clay/shale stability are explained in detail.The mechanisms,impacts,and advances achieved when SPs are added to drilling fluids are also described.The typical challenges encountered by SPs when deployed in drilling fluids and their advantages and drawbacks are also discussed.Economic issues also impact the applications of SPs in drilling fluids.Consequently,the cost of the most relevant SPs,and the monomers used in their synthesis,are assessed.Environmental impacts of SPs when deployed in drilling fluids,and their manufacturing processes are identified,together with advances in SP-treatment methods aimed at reducing those impacts.Recommendations for required future research addressing SP property and performance gaps are provided.
基金The financial supports from the National Natural Science Foundation of China (22178059, 22208054 and 22072019)Natural Science Foundation of Fujian Province, China (2020J01513)+1 种基金Sinochem Quanzhou Energy Technology Co., Ltd. (ZHQZKJ-19-F-ZS0076)Qingyuan Innovation Laboratory (00121002)
文摘Zeolite catalysts have found extensive applications in the synthesis of various fine chemicals.However,the micropores of zeolites impose diffusion limitations on bulky molecules,greatly reducing the catalytic efficiency.Herein,we explore an economic and environmentally friendly method for synthesizing hierarchical NaX zeolite that exhibits improved catalytic performance in the Knoevenagel condensation reaction for producing the useful fine chemical 2-cyano-3-phenylacrylate.The synthesis was achieved via a low-temperature activation of kaolinite and subsequent in-situ transformation strategy without any template or seed.Systematic characterizations reveal that the synthesized NaX zeolite has both intercrystalline and intra-crystalline mesopores,smaller crystal size,and larger external specific surface area compared to commercial NaX zeolite.Detailed mechanism investigations show that the inter-crystalline mesopores are generated by stacking smaller crystals formed from in-situ crystallization of the depolymerized kaolinite,and the intra-crystalline mesopores are inherited from the pores in the depolymerized kaolinite.This synthesis strategy provides an energy-saving and effective way to construct hierarchical zeolites,which may gain wide applications in fine chemical manufacturing.
文摘Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.
基金financially supported by the National Natural Science Foundation of China(Grant No.51890914)。
文摘Different from oil and gas production,hydrate reservoirs are shallow and unconsolidated,whose mechanical properties deteriorate with hydrate decomposition.Therefore,the formations will undergo significant subsidence during depressurization,which will destroy the original force state of the production well.However,existing research on the stability of oil and gas production wells assumes the formation to be stable,and lacks consideration of the force exerted on the hydrate production well by formation subsidence caused by hydrate decomposition during production.To fill this gap,this paper proposes an analytical method for the dynamic evolution of the stability of hydrate production well considering the effects of hydrate decomposition.Based on the mechanical model of the production well,the basis for stability analysis has been proposed.A multi-field coupling model of the force state of the production well considering the effect of hydrate decomposition and formation subsidence is established,and a solver is developed.The analytical approach is verified by its good agreement with the results from the numerical method.A case study found that the decomposition of hydrate will increase the pulling-down force and reduce the supporting force,which is the main reason for the stability deterioration.The higher the initial hydrate saturation,the larger the reservoir thickness,and the lower the production pressure,the worse the stability or even instability.This work can provide a theoretical reference for the stability maintaining of the production well.
文摘The accurate prediction of the friction angle of clays is crucial for assessing slope stability in engineering applications.This study addresses the importance of estimating the friction angle and presents the development of four soft computing models:YJ-FPA-MLPnet,YJ-CRO-MLPnet,YJ-ACOC-MLPnet,and YJCSA-MLPnet.First of all,the Yeo-Johnson(YJ)transformation technique was used to stabilize the variance of data and make it more suitable for parametric statistical models that assume normality and equal variances.This technique is expected to improve the accuracy of friction angle prediction models.The friction angle prediction models then utilized multi-layer perceptron neural networks(MLPnet)and metaheuristic optimization algorithms to further enhance performance,including flower pollination algorithm(FPA),coral reefs optimization(CRO),ant colony optimization continuous(ACOC),and cuckoo search algorithm(CSA).The prediction models without the YJ technique,i.e.FPA-MLPnet,CRO-MLPnet,ACOC-MLPnet,and CSA-MLPnet,were then compared to those with the YJ technique,i.e.YJ-FPA-MLPnet,YJ-CRO-MLPnet,YJ-ACOC-MLPnet,and YJ-CSA-MLPnet.Among these,the YJ-CRO-MLPnet model demonstrated superior reliability,achieving an accuracy of up to 83%in predicting the friction angle of clay in practical engineering scenarios.This improvement is significant,as it represents an increase from 1.3%to approximately 20%compared to the models that did not utilize the YJ transformation technique.
基金jointly supported by the National Key Research and Development Program of China(Grant No.2022YFE0106500)Jiangsu Science Fund for Distinguished Young Scholars(Grant No.BK20200040)。
文摘The pan-Arctic is confronted with air pollution transported from lower latitudes.Observations have shown that aerosols help increase plant photosynthesis through the diffuse radiation fertilization effects(DRFEs).While such DRFEs have been explored at low to middle latitudes,the aerosol impacts on pan-Arctic ecosystems and the contributions by anthropogenic and natural emission sources remain less quantified.Here,we perform regional simulations at 0.2o×0.2ousing a well-validated vegetation model(Yale Interactive terrestrial Biosphere,YIBs)in combination with multi-source of observations to quantify the impacts of aerosol DRFEs on the net primary productivity(NPP)in the pan-Arctic during 2001-19.Results show that aerosol DRFEs increase pan-Arctic NPP by 2.19 Pg C(12.8%)yr^(-1)under clear-sky conditions,in which natural and anthropogenic sources contribute to 8.9% and 3.9%,respectively.Under all-sky conditions,such DRFEs are largely dampened by cloud to only 0.26 Pg C(1.24%)yr^(-1),with contributions of 0.65% by natural and 0.59% by anthropogenic species.Natural aerosols cause a positive NPP trend of 0.022% yr^(-1)following the increased fire activities in the pan-Arctic.In contrast,anthropogenic aerosols induce a negative trend of-0.01% yr^(-1)due to reduced emissions from the middle latitudes.Such trends in aerosol DRFEs show a turning point in the year of 2007 with more positive NPP trends by natural aerosols but negative NPP trends by anthropogenic aerosols thereafter.Though affected by modeling uncertainties,this study suggests a likely increasing impact of aerosols on terrestrial ecosystems in the pan-Arctic under global warming.
基金supported by the National Natural Science Foundation of China(52325001,52170009,and 52091542)the National Key Research and Development Program of China(2021YFC3200700)+3 种基金the Program of Shanghai Academic Research Leader,China(21XD1424000)the International Cooperation Project of Shanghai Science and Technology Commission(20230714100)the Key-Area Research and Development Program of Guangdong Province(2020B1111350001)Tongji University Youth 100 Program.
文摘Tracing the contamination origins in water sources and identifying the impacts of natural and human processes are essential for ecological safety and public health.However,current analysis approaches are not ideal,as they tend to be laborious,time-consuming,or technically difficult.Disinfection byproducts(DBPs)are a family of well-known secondary pollutants formed by the reactions of chemical disinfectants with DBP precursors during water disinfection treatment.Since DBP precursors have various origins(e.g.,natural,domestic,industrial,and agricultural sources),and since the formation of DBPs from different precursors in the presence of specific disinfectants is distinctive,we argue that DBPs and DBP precursors can serve as alternative indicators to assess the contamination in water sources and identify pollution origins.After providing a retrospective of the origins of DBPs and DBP precursors,as well as the specific formation patterns of DBPs from different precursors,this article presents an overview of the impacts of various natural and anthropogenic factors on DBPs and DBP precursors in drinking water sources.In practice,the DBPs(i.e.,their concentration and speciation)originally present in source water and the DBP precursors determined using DBP formation potential tests—in which water samples are dosed with a stoichiometric excess of specific disinfectants in order to maximize DBP formation under certain reaction conditions—can be considered as alternative metrics.When jointly used with other water quality parameters(e.g.,dissolved organic carbon,dissolved organic nitrogen,fluorescence,and molecular weight distribution)and specific contaminants of emerging concern(e.g.,certain pharmaceuticals and personal care products),DBPs and DBP precursors in drinking water sources can provide a more comprehensive picture of water pollution for better managing water resources and ensuring human health.