In this paper, incised valley filling deposits, which formed an important pathway system for long-distance hydrocarbon migration, are discussed in detail based on core and logging data. The sequence SQy23 of the Creta...In this paper, incised valley filling deposits, which formed an important pathway system for long-distance hydrocarbon migration, are discussed in detail based on core and logging data. The sequence SQy23 of the Cretaceous Yaojia Formation is the main hydrocarbon-bearing layer in the Fulaerji Oilfield. The hydrocarbon source of the oilfield is the Qijia-Gulong Sag which is about 80 km away from the Fulaerji Oilfield. The transport layer of long-distance hydrocarbon migration is the overlapped sandstone complex which fills the incised valley. The incised valley developed during the depositional period from the late Qingshankou Formation to the early Yaojia Formation of Cretaceous （SQqna-SQy0 was about 70 km long and 20 km wide, and extended in the NW-SE direction. The overlapped filling of the incised valley mainly occurred in the expanding system tract of the third-order sequence SQy23 （ESTy23）. Towards the basin, incised valley filling deposits overlapped on the delta developed in the early period, and towards the basin margin, incised valley filling deposits were covered by the shore-shallow lacustrine sandy beach bar developed in the maximum flooding period. All of the delta, the incised valley filling and the shore-shallow sandy beach bar are sandstone-rich, and have high porosity and permeability, and can form an effective hydrocarbon migration and accumulation system. Deltaic sand bodies collected and pumped hydrocarbon from the active source, incised valley filling depositional system completed the long-distance hydrocarbon migration, and lithological traps of shore-shallow lacustrine sandy beach bar accumulated hydrocarbon. The incised valley filling sequences are multi-cycle： an integrated shortterm filling cycle was developed on the erosion surface, and the sequences upward were mud-gravel stone, medium-fine sandstone containing terrigenous gravels and muddy pebbles with cross bedding, silty mudstone with ripple bedding, and mudstone. The incised valley filling deposits are characterized by a strong heterogeneity and the main hydrocarbon migration pathway is the medium-fine sandstone interval.展开更多
Research on the distribution of mantle CO_(2)should involve comprehensive analysis from CO_(2)source to accumulation.The crust-mantle pathway system is the key controlling factor of the distribution of mantle CO_(2),b...Research on the distribution of mantle CO_(2)should involve comprehensive analysis from CO_(2)source to accumulation.The crust-mantle pathway system is the key controlling factor of the distribution of mantle CO_(2),but has received little attention.The pathway system and controlling factors of CO_(2)distribution in the Bohai Sea are analyzed using data on fault styles and information on the mantle and lithosphere.The relation between volcanic rocks and the distribution of mantle CO_(2)is reassessed using age data for CO_(2)accumulations.The distribution of mantle CO_(2)is controlled by uplift of the asthenosphere and upper mantle,magma conduits in the mantle and fault systems in the crust.Uplifted regions of the asthenosphere are accumulation areas for CO_(2).The area with uplift of the Moho exhibits accumulation of mantle CO_(2)at depth.CO_(2)was mainly derived from vertical migration through the upper mantle and lower crust.The fault style in the upper crust controls the distance of horizontal migration and the locations of CO_(2)concentrations.The distribution of mantle CO_(2)and volcanic rocks are not the same,but both probably followed the same pathways sometimes.Mantle CO_(2)in the Bohai Sea is concentrated in the Bozhong sag and the surrounding area,particularly in a trap that formed before 5.1 Ma and is connected to crustal faults(the Bozhang faults)and lithospheric faults(the Tanlu faults).展开更多
The large-scale exploitation of vanadium(Ⅴ) bearing minerals has led to a massive accumulation of Ⅴ tailings, of which Ⅴ pollution poses severe ecological risks. Although the mechanisms of Ⅴ stress to the microbia...The large-scale exploitation of vanadium(Ⅴ) bearing minerals has led to a massive accumulation of Ⅴ tailings, of which Ⅴ pollution poses severe ecological risks. Although the mechanisms of Ⅴ stress to the microbial community have been reported, the influential pathways in a multi-medium-containing system, for example, the soil-tailings-groundwater system,are unknown. The dynamic redox conditions and substance exchange within the system exhibited complex Ⅴ stress on the local microbial communities. In this study, the influence pathways of Ⅴ stress to the microbial community in the soil-tailings-groundwater system were first investigated. High Ⅴ contents were observed in groundwater(139.2 ± 0.15 μg/L) and soil(98.0–323.8 ± 0.02 mg/kg), respectively. Distinct microbial composition was observed for soil and groundwater, where soil showed the highest level of diversity and richness. Firmicutes, Proteobacteria, Actinobacteria, and Acidobacteria were dominant in soil and groundwater with a sum relative abundance of around 80 %. Based on redundancy analysis and structural equation models, Ⅴ was one of the vital driving factors affecting microbial communities. Groundwater microbial communities were influenced by Ⅴ via Cr, dissolved oxygen, and total nitrogen, while Fe, Mn, and total phosphorus were the key mediators for Ⅴ to affect soil microbial communities. Ⅴ affected the microbial community via metabolic pathways related to carbonaceous matter, which was involved in the establishment of survival strategies for metal stress. This study provides novel insights into the influence pathways of Ⅴ on the microorganisms in tailings reservoir for pollution bioremediation.展开更多
This article investigates the development process and current status of policy-based agricultural insurance in Chongqing.Based on recent data-including premium income,compensation amounts,the number of insured househo...This article investigates the development process and current status of policy-based agricultural insurance in Chongqing.Based on recent data-including premium income,compensation amounts,the number of insured households,and insurance penetration,the article analyzes the primary challenges faced in the system's operation and proposes recommendations from two dimensions:institutional optimization and practical interventions.These recommendations include establishing a differentiated participation incentive mechanism,optimizing the composition of insurance products,enhancing risk diversification and reinsurance systems,creating an agricultural disaster risk reserve fund,developing a dynamic fiscal subsidy distribution mechanism based on risk and performance,improving information-sharing platforms,strengthening the rural grassroots power grid infrastructure,and accelerating the adoption of modern technologies in underwriting and claims settlement processes.The findings suggest that the coordinated advancement of institutional optimization and technological empowerment can substantially enhance the inclusiveness,sustainability,and operational efficiency of policy-based agricultural insurance in Chongqing,thereby providing substantial support for agricultural modernization and the Rural Revitalization Strategy.展开更多
The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically revie...The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.展开更多
Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-b...Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.展开更多
BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling p...BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.展开更多
The elimination of neonicotinoids(NEOs)from water has been a research priority due to their threats to human health and ecosystems.In this study,we established the heterogeneous peroxymonosulfate(PMS)activation system...The elimination of neonicotinoids(NEOs)from water has been a research priority due to their threats to human health and ecosystems.In this study,we established the heterogeneous peroxymonosulfate(PMS)activation system using manganese catalyst(Mn NC)and cobalt catalyst(Co NC)to trigger the nonradical oxidation and synergistic oxidation pathway,respectively to remove NEOs.The results showed that the nonradical oxidation system exhibited superior NEOs degradation capability.The composition of organic pollutants in wastewater significantly impacted subsequent degradation processes.The charge distribution and reaction sites of various NEOs were analyzed using density functional theory(DFT)calculations,and it demonstrated the electron distribution and activity of NEOs were significantly influenced by the type and number of substituents.Nitro group(–NO_(2))and cyanide group(–C≡N)were identified as strong electron-withdrawing groups and prone to be attacked by negatively charged radicals.The transformation of NEOs was analyzed,and result showed that the C and N sites adjacent to the nitro group and cyanide group were more susceptible to oxidation attacks.S and N atoms,which possess strong electronegativity and high electron cloud density,were identified as key active sites in the degradation pathway.The outcomes of this study provide valuable guidance for the oriented regulation of oxidation pathways towards efficient removal of NEOs in water.展开更多
Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand...Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.展开更多
The presented research illustrates the applicability and productiveness of the systematic literature review methodology, a non-empirical methodology in the geological sciences, particularly volcanology. The systematic...The presented research illustrates the applicability and productiveness of the systematic literature review methodology, a non-empirical methodology in the geological sciences, particularly volcanology. The systematic literature review methodology is a replicable, rigorous, and transparent methodology for synthesizing existing literature to answer questions on a specific topic. The synthesis allows for knowledge consolidation, such as identifying knowledge gaps. In our illustration of this methodology, we focused on the expanding knowledge about the magma pathway at Mount Cameroon, one of Africa’s active volcanoes. Our synthesis of the relevant international geoscience research literature is based on the framework of knowledge about the magma pathway beneath a typical basaltic volcano. The framework has three primary components: magma supply, storage, and transport to erupting vents. Across these components is a total of twelve secondary components. The result is a previously non-existent and fragmented overall understanding of the magma pathway at Mount Cameroon. The gaps in the understanding (such as in the magma supply rates, timescales of chamber processes, and magma ascent rates) may be addressed in future research. Another key implication of the presented research lies in the proof of concept of the systematic literature review methodology as an applicable qualitative research methodology in the study of volcanoes.展开更多
Cancer represents a significant disease that profoundly impacts human health and longevity.Projections indicate a 47%increase in the global cancer burden by 2040 compared to 2020,accompanied by a further rise in the a...Cancer represents a significant disease that profoundly impacts human health and longevity.Projections indicate a 47%increase in the global cancer burden by 2040 compared to 2020,accompanied by a further rise in the associated economic burden.Consequently,there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer.Natural products(NPs)play a crucial role in the identification and development of anticancer therapeutics.This study identified ustusolate E(UE)and its analog 11α-hydroxy-ustusolate E(HUE)from strain Aspergillus calidoustus TJ403-EL05,and examined their antitumor activities and mechanisms of action.The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS(human gastric cancer cells)and 786-O(human renal clear cell carcinoma cells),induced irreversible DNA damage,blocked the cell cycle at the G_(2)/M phase,and further induced apoptosis in tumor cells.To the best of the authors’knowledge,this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms.The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.展开更多
Extreme ozone pollution events(EOPEs)are associated with synoptic weather patterns(SWPs)and pose severe health and ecological risks.However,a systematic investigation of themeteorological causes,transport pathways,and...Extreme ozone pollution events(EOPEs)are associated with synoptic weather patterns(SWPs)and pose severe health and ecological risks.However,a systematic investigation of themeteorological causes,transport pathways,and source contributions to historical EOPEs is still lacking.In this paper,the K-means clustering method is applied to identify six dominant SWPs during the warm season in the Yangtze River Delta(YRD)region from 2016 to 2022.It provides an integrated analysis of the meteorological factors affecting ozone pollution in Hefei under different SWPs.Using the WRF-FLEXPART model,the transport pathways(TPPs)and geographical sources of the near-surface air masses in Hefei during EOPEs are investigated.The results reveal that Hefei experienced the highest ozone concentration(134.77±42.82μg/m^(3)),exceedance frequency(46 days(23.23%)),and proportion of EOPEs(21 instances,47.7%)under the control of peripheral subsidence of typhoon(Type 5).Regional southeast winds correlated with the ozone pollution in Hefei.During EOPEs,a high boundary layer height,solar radiation,and temperature;lowhumidity and cloud cover;and pronounced subsidence airflow occurred over Hefei and the broader YRD region.The East-South(E_S)patterns exhibited the highest frequency(28 instances,65.11%).Regarding the TPPs and geographical sources of the near-surface air masses during historical EOPEs.The YRD was the main source for land-originating air masses under E_S patterns(50.28%),with Hefei,southern Anhui,southern Jiangsu,and northern Zhejiang being key contributors.These findings can help improve ozone pollution early warning and control mechanisms at urban and regional scales.展开更多
Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through iso...Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through isobaric tags for relative and absolute quantitation(iTRAQ)coupled with liquid chromatography-tandem mass spectrometry(LC-MS/MS)phosphoproteomic analysis of 14 GC and gastric epithelial cell lines,we discovered the discoidin domain receptor tyrosine kinase 1(DDR1)as a top potential drug target out of 40 tyrosine kinases detected along with over 1000 phosphoproteins profiled.The DDR1 protein and mRNA levels were upregulated in GC cells concurrent with DDR1 gene amplification.Immunohistochemistry staining of more than 200 clinical samples revealed that DDR1 was overexpressed in approximately 41%and 48%of the intestinal and diffuse types of GC cases,respectively,compared with only 3.5%in normal tissues.Higher DDR1 expression was associated with poor prognosis.In cellular models,DDR1 overexpression led to accelerated proliferation,invasion,and malignant transformation,putatively via inhibition of the Hippo pathway and consequent activation of YAP-TEAD target gene expression.Notably,DDR1-overexpressing GC cells exhibited high vulnerability to selective DDR1 inhibitors.The present study provides preclinical support for the application of DDR1-selective inhibitors in DDR1-overexpressing GC.展开更多
Minocycline has been widely used in clinical treatment and its residues were considered to have environmental safety risks due to complex chemical structure.Therefore,it is necessary to find an efficient and environme...Minocycline has been widely used in clinical treatment and its residues were considered to have environmental safety risks due to complex chemical structure.Therefore,it is necessary to find an efficient and environmentally friendly method to remove minocycline from the environment.This study screened and isolated a minocycline degrading strain DM13 from the activated sludge for municipal sewage pipeline,and optimized the biodegradation of minocycline by DM13 under various environmental conditions.The maximum biodegradation efficiency of 50 mg/L minocycline reached 93%at 72 h with the temperature of 30℃,the initial pH of 7.0,and the inoculation rate of 3%.Two potential biotransformation pathways were proposed,including deamination,demethylation,and decarbonylation.The acute toxicity assessment showed that the biotransformation products of minocycline had lower toxicity than the parent compound.In addition,the first-generation tetracycline antibiotics could be removed,suggesting that strain DM13 has the potential for application in treating antibiotic wastewater.展开更多
Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-cateni...Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.展开更多
BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear f...BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.展开更多
Low-density lipoprotein receptor-related protein 1(LRP1)is a multifunctional endocytic receptor whose dysfunction is linked to developmental dysplasia of the hip,osteoporosis and osteoarthritis.Our work addresses the ...Low-density lipoprotein receptor-related protein 1(LRP1)is a multifunctional endocytic receptor whose dysfunction is linked to developmental dysplasia of the hip,osteoporosis and osteoarthritis.Our work addresses the critical question of how these skeletal pathologies emerge.Here,we show the abundant expression of LRP1 in skeletal progenitor cells at mouse embryonic stage E10.5 and onwards,especially in the perichondrium,the stem cell layer surrounding developing limbs essential for bone formation.Lrp1 deficiency in these stem cells causes joint fusion,malformation of cartilage/bone template and markedly delayed or lack of primary ossification.展开更多
Objective:The occurrence and development of atrial fibrillation(AF)are influenced by the autonomic nervous system and inflammation.Acupuncture is an effective treatment for AF.This study explored the protective effect...Objective:The occurrence and development of atrial fibrillation(AF)are influenced by the autonomic nervous system and inflammation.Acupuncture is an effective treatment for AF.This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.Methods:Male Sprague-Dawley rats(n=130)were randomly divided into blank control(Con),sham operation(Sham),AF,and acupuncture treatment(Acu)groups.A paroxysmal AF model was established by rapid atrial pacing through the jugular vein.Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint(PC6)for 20 min daily for seven days.The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture.The AF induction rate,AF duration,cardiac electrophysiological parameters,and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals.After the intervention,the rats were euthanized,and atrial morphology was assessed using haematoxylin and eosin staining.The expression of macrophage F4/80 antigen(F4/80)and cluster of differentiation(CD)86 in atrial myocardial tissue was detected using immunohistochemistry,immunofluorescence and flow cytometry.The expression levels or contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-a(TNF-a),a7 nicotinic acetylcholine receptor(a7nAChR),phosphorylated Janus kinase 2(p-JAK2),and phosphorylated signal transducer and activator of transcription 3(p-STAT3)in atrial myocardial tissue were detected using Western blotting,reverse transcription-quantitative polymerase chain reaction,or enzyme-linked immunosorbent assay.The role of a7nAChR in acupuncture treatment was verified by intraperitoneal injection of the a7nAChR antagonist methyllycaconitine(MLA).Results:Compared with the AF group,acupuncture significantly reduced AF duration and induction rate,improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance.It also decreased the pro-inflammatory M1 macrophage proportion,alleviating myocardial injury and infiltration.MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect.Results suggest that acupuncture triggers the a7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.Conclusion:Acupuncture significantly reduced the AF induction rate,shortened AF duration,improved cardiac electrophysiological parameters,enhanced vagus nerve activity,and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF.展开更多
The electrochemical reduction of carbon dioxide(CO_(2))into value-added chemicals and fuels has been extensively studied as a promising strategy for mitigating environmental issues and achieving sustainable energy con...The electrochemical reduction of carbon dioxide(CO_(2))into value-added chemicals and fuels has been extensively studied as a promising strategy for mitigating environmental issues and achieving sustainable energy conversion.Substantial efforts have been made to improve the understanding of CO_(2)reduction reaction(CO_(2)RR)mechanisms by computational and spectroscopic studies.An in-depth understanding of CO_(2)RR mechanism can provide the guidance and criteria for designing high-efficiency catalysts,and hence,steering CO_(2)RR to desired products.This review systematically discusses the formation mechanisms and reaction pathways of various CO_(2)RR products,including C_(1)products(CO,HCOOH,and CH_(4)),C_(2)products(C_(2)H_(4),C_(2)H_(5)OH,and CH_(3)COOH),and C_(3+)products(C_(3)H_(6),C_(3)H_(7)OH,and others).The reaction pathways are elucidated by analyzing the adsorption behavior,energy barriers,and intermediate coupling steps involved in the generation of each product.Particular emphasis is placed on the key intermediates,such as^(*)OCHO,^(*)COOH,^(*)CO,^(*)OCCOH,and^(*)CCO,which play crucial roles in determining the product selectivity.The effects of catalyst composition,morphology,and electronic structure on the adsorption and activation of these intermediates are also discussed.Moreover,advanced characterization techniques,including in-situ spectroscopy and isotopic labeling experiments,are highlighted for their contributions to unraveling the reaction mechanisms.The review aims to provide critical insights to reveal the activity-determining para meters and underlying CO_(2)RR mechanisms,which will guide the rational design of next-generation electrocatalysts for selective CO^(2)RR towards high-value products.展开更多
Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microgl...Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.展开更多
文摘In this paper, incised valley filling deposits, which formed an important pathway system for long-distance hydrocarbon migration, are discussed in detail based on core and logging data. The sequence SQy23 of the Cretaceous Yaojia Formation is the main hydrocarbon-bearing layer in the Fulaerji Oilfield. The hydrocarbon source of the oilfield is the Qijia-Gulong Sag which is about 80 km away from the Fulaerji Oilfield. The transport layer of long-distance hydrocarbon migration is the overlapped sandstone complex which fills the incised valley. The incised valley developed during the depositional period from the late Qingshankou Formation to the early Yaojia Formation of Cretaceous （SQqna-SQy0 was about 70 km long and 20 km wide, and extended in the NW-SE direction. The overlapped filling of the incised valley mainly occurred in the expanding system tract of the third-order sequence SQy23 （ESTy23）. Towards the basin, incised valley filling deposits overlapped on the delta developed in the early period, and towards the basin margin, incised valley filling deposits were covered by the shore-shallow lacustrine sandy beach bar developed in the maximum flooding period. All of the delta, the incised valley filling and the shore-shallow sandy beach bar are sandstone-rich, and have high porosity and permeability, and can form an effective hydrocarbon migration and accumulation system. Deltaic sand bodies collected and pumped hydrocarbon from the active source, incised valley filling depositional system completed the long-distance hydrocarbon migration, and lithological traps of shore-shallow lacustrine sandy beach bar accumulated hydrocarbon. The incised valley filling sequences are multi-cycle： an integrated shortterm filling cycle was developed on the erosion surface, and the sequences upward were mud-gravel stone, medium-fine sandstone containing terrigenous gravels and muddy pebbles with cross bedding, silty mudstone with ripple bedding, and mudstone. The incised valley filling deposits are characterized by a strong heterogeneity and the main hydrocarbon migration pathway is the medium-fine sandstone interval.
基金supported by the Major Program of the National Natural Science Foundation of China(41790453)the Natural Science Foundation of Jilin Province(20170101001JC)+1 种基金the National Natural Science Foundation of China(41472304)the National Science and Technology Major Project of the Ministry of Science and Technology of China(2016ZX05026-004-001)。
文摘Research on the distribution of mantle CO_(2)should involve comprehensive analysis from CO_(2)source to accumulation.The crust-mantle pathway system is the key controlling factor of the distribution of mantle CO_(2),but has received little attention.The pathway system and controlling factors of CO_(2)distribution in the Bohai Sea are analyzed using data on fault styles and information on the mantle and lithosphere.The relation between volcanic rocks and the distribution of mantle CO_(2)is reassessed using age data for CO_(2)accumulations.The distribution of mantle CO_(2)is controlled by uplift of the asthenosphere and upper mantle,magma conduits in the mantle and fault systems in the crust.Uplifted regions of the asthenosphere are accumulation areas for CO_(2).The area with uplift of the Moho exhibits accumulation of mantle CO_(2)at depth.CO_(2)was mainly derived from vertical migration through the upper mantle and lower crust.The fault style in the upper crust controls the distance of horizontal migration and the locations of CO_(2)concentrations.The distribution of mantle CO_(2)and volcanic rocks are not the same,but both probably followed the same pathways sometimes.Mantle CO_(2)in the Bohai Sea is concentrated in the Bozhong sag and the surrounding area,particularly in a trap that formed before 5.1 Ma and is connected to crustal faults(the Bozhang faults)and lithospheric faults(the Tanlu faults).
基金supported by the National Natural Science Foundation of China(No.42377415)the Natural Science Foundation of Sichuan Province(No.2023NSFSC0811),Sichuan Science and Technology Program(Nos.2021JDTD0013 and 2021YFQ0066)+1 种基金the Science and Technology Major Project of Xizhang Autonomous Region of China(No.XZ202201ZD0004G06)the Everest Scientific Research Program(No.80000-2023ZF11405).
文摘The large-scale exploitation of vanadium(Ⅴ) bearing minerals has led to a massive accumulation of Ⅴ tailings, of which Ⅴ pollution poses severe ecological risks. Although the mechanisms of Ⅴ stress to the microbial community have been reported, the influential pathways in a multi-medium-containing system, for example, the soil-tailings-groundwater system,are unknown. The dynamic redox conditions and substance exchange within the system exhibited complex Ⅴ stress on the local microbial communities. In this study, the influence pathways of Ⅴ stress to the microbial community in the soil-tailings-groundwater system were first investigated. High Ⅴ contents were observed in groundwater(139.2 ± 0.15 μg/L) and soil(98.0–323.8 ± 0.02 mg/kg), respectively. Distinct microbial composition was observed for soil and groundwater, where soil showed the highest level of diversity and richness. Firmicutes, Proteobacteria, Actinobacteria, and Acidobacteria were dominant in soil and groundwater with a sum relative abundance of around 80 %. Based on redundancy analysis and structural equation models, Ⅴ was one of the vital driving factors affecting microbial communities. Groundwater microbial communities were influenced by Ⅴ via Cr, dissolved oxygen, and total nitrogen, while Fe, Mn, and total phosphorus were the key mediators for Ⅴ to affect soil microbial communities. Ⅴ affected the microbial community via metabolic pathways related to carbonaceous matter, which was involved in the establishment of survival strategies for metal stress. This study provides novel insights into the influence pathways of Ⅴ on the microorganisms in tailings reservoir for pollution bioremediation.
基金Supported by Chongqing Social Science Planning Project(Doctoral Project)"Research Support on the Impact of Policy-based Agricultural Insurance on the Production Behavior of Chinese Farmers"(2020BS39).
文摘This article investigates the development process and current status of policy-based agricultural insurance in Chongqing.Based on recent data-including premium income,compensation amounts,the number of insured households,and insurance penetration,the article analyzes the primary challenges faced in the system's operation and proposes recommendations from two dimensions:institutional optimization and practical interventions.These recommendations include establishing a differentiated participation incentive mechanism,optimizing the composition of insurance products,enhancing risk diversification and reinsurance systems,creating an agricultural disaster risk reserve fund,developing a dynamic fiscal subsidy distribution mechanism based on risk and performance,improving information-sharing platforms,strengthening the rural grassroots power grid infrastructure,and accelerating the adoption of modern technologies in underwriting and claims settlement processes.The findings suggest that the coordinated advancement of institutional optimization and technological empowerment can substantially enhance the inclusiveness,sustainability,and operational efficiency of policy-based agricultural insurance in Chongqing,thereby providing substantial support for agricultural modernization and the Rural Revitalization Strategy.
基金supported by Yuan Du Scholars,Clinical Research Center of Affiliated Hospital of Shandong Second Medical University,No.2022WYFYLCYJ02Weifang Key Laboratory,Weifang Science and Technology Development Plan Project Medical Category,No.2022YX093.
文摘The cGAS–STING pathway plays an important role in ischemia-reperfusion injury in the heart,liver,brain,and kidney,but its role and mechanisms in cerebral ischemia-reperfusion injury have not been systematically reviewed.Here,we outline the components of the cGAS–STING pathway and then analyze its role in autophagy,ferroptosis,cellular pyroptosis,disequilibrium of calcium homeostasis,inflammatory responses,disruption of the blood–brain barrier,microglia transformation,and complement system activation following cerebral ischemia-reperfusion injury.We further analyze the value of cGAS–STING pathway inhibitors in the treatment of cerebral ischemia-reperfusion injury and conclude that the pathway can regulate cerebral ischemia-reperfusion injury through multiple mechanisms.Inhibition of the cGAS–STING pathway may be helpful in the treatment of cerebral ischemia-reperfusion injury.
文摘Alzheimer's disease is a common neurodegenerative disorder in older adults.Despite its prevalence,its pathogenesis remains unclea r.In addition to the most widely accepted causes,which in clude excessive amyloid-beta aggregation,tau hyperphosphorylation,and deficiency of the neurotransmitter acetylcholine,numerous studies have shown that the dopaminergic system is also closely associated with the occurrence and development of this condition.Dopamine is a crucial catecholaminergic neurotransmitter in the human body.Dopamine-associated treatments,such as drugs that target dopamine receptor D and dopamine analogs,can improve cognitive function and alleviate psychiatric symptoms as well as ameliorate other clinical manifestations.Howeve r,therapeutics targeting the dopaminergic system are associated with various adverse reactions,such as addiction and exacerbation of cognitive impairment.This review summarizes the role of the dopaminergic system in the pathology of Alzheimer's disease,focusing on currently available dopamine-based therapies for this disorder and the common side effects associated with dopamine-related drugs.The aim of this review is to provide insights into the potential connections between the dopaminergic system and Alzheimer's disease,thus helping to clarify the mechanisms underlying the condition and exploring more effective therapeutic options.
文摘BACKGROUND Simulated microgravity environment can lead to gastrointestinal motility disturbance.The pathogenesis of gastrointestinal motility disorders is closely related to the stem cell factor(SCF)/c-kit signaling pathway associated with intestinal flora and Cajal stromal cells.Moreover,intestinal flora can also affect the regulation of SCF/c-kit signaling pathway,thus affecting the expression of Cajal stromal cells.Cajal cells are the pacemakers of gastrointestinal motility.AIM To investigate the effects of Bifidobacterium lactis(B.lactis)BLa80 on the intestinal flora of rats in simulated microgravity and on the gastrointestinal motility-related SCF/c-kit pathway.METHODS The internationally recognized tail suspension animal model was used to simulate the microgravity environment,and 30 rats were randomly divided into control group,tail suspension group and drug administration tail suspension group with 10 rats in each group for a total of 28 days.The tail group was given B.lactis BLa80 by intragastric administration,and the other two groups were given water intragastric administration,the concentration of intragastric administration was 0.1 g/mL,and each rat was 1 mL/day.Hematoxylin&eosin staining was used to observe the histopathological changes in each segment of the intestine of each group,and the expression levels of SCF,c-kit,extracellular signal-regulated kinase(ERK)and p-ERK in the gastric antrum of each group were detected by Western blotting and PCR.The fecal flora and mucosal flora of rats in each group were detected by 16S rRNA.RESULTS Simulated microgravity resulted in severe exfoliation of villi of duodenum,jejunum and ileum in rats,marked damage,increased space between villi,loose arrangement,shortened columnar epithelium of colon,less folds,narrower mucosal thickness,reduced goblet cell number and crypts,and significant improvement after probiotic intervention.Simulated microgravity reduced the expressions of SCF and c-kit,and increased the expressions of ERK and P-ERK in the gastric antrum of rats.However,after probiotic intervention,the expressions of SCF and ckit were increased,while the expressions of ERK and P-ERK were decreased,with statistical significance(P<0.05).In addition,simulated microgravity can reduce the operational taxonomic unit(OTU)of the overall intestinal flora of rats,B.lactis BLa80 can increase the OTU of rats,simulated microgravity can reduce the overall richness and diversity of stool flora of rats,increase the abundance of firmicutes in stool flora of rats,and reduce the abundance of Bacteroides in stool flora of rats,most of which are mainly beneficial bacteria.Simulated microgravity can increase the overall richness and diversity of mucosal flora,increase the abundance of Bacteroides and Desulphurides in the rat mucosal flora,and decrease the abundance of firmicutes,most of which are proteobacteria.After probiotics intervention,the overall Bacteroidetes trend in simulated microgravity rats was increased.CONCLUSION B.lactis BLa80 can ameliorate intestinal mucosal injury,regulate intestinal flora,inhibit ERK expression,and activate the SCF/c-kit signaling pathway,which may have a facilitating effect on gastrointestinal motility in simulated microgravity rats.
基金funded by National Natural Science Foundation of China(No.42177382)。
文摘The elimination of neonicotinoids(NEOs)from water has been a research priority due to their threats to human health and ecosystems.In this study,we established the heterogeneous peroxymonosulfate(PMS)activation system using manganese catalyst(Mn NC)and cobalt catalyst(Co NC)to trigger the nonradical oxidation and synergistic oxidation pathway,respectively to remove NEOs.The results showed that the nonradical oxidation system exhibited superior NEOs degradation capability.The composition of organic pollutants in wastewater significantly impacted subsequent degradation processes.The charge distribution and reaction sites of various NEOs were analyzed using density functional theory(DFT)calculations,and it demonstrated the electron distribution and activity of NEOs were significantly influenced by the type and number of substituents.Nitro group(–NO_(2))and cyanide group(–C≡N)were identified as strong electron-withdrawing groups and prone to be attacked by negatively charged radicals.The transformation of NEOs was analyzed,and result showed that the C and N sites adjacent to the nitro group and cyanide group were more susceptible to oxidation attacks.S and N atoms,which possess strong electronegativity and high electron cloud density,were identified as key active sites in the degradation pathway.The outcomes of this study provide valuable guidance for the oriented regulation of oxidation pathways towards efficient removal of NEOs in water.
基金supported by the National Natural Science Foundation of China(Key Program),No.11932013the National Natural Science Foundation of China(General Program),No.82272255+2 种基金Armed Police Force High-Level Science and Technology Personnel ProjectThe Armed Police Force Focuses on Supporting Scientific and Technological Innovation TeamsKey Project of Tianjin Science and Technology Plan,No.20JCZDJC00570(all to XC)。
文摘Spinal cord injury involves non-reversible damage to the central nervous system that is characterized by limited regenerative capacity and secondary inflammatory damage.The expression of the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis exhibits significant differences before and after injury.Recent studies have revealed that the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis is closely associated with secondary inflammatory responses and the recruitment of immune cells following spinal cord injury,suggesting that this axis is a novel target and regulatory control point for treatment.This review comprehensively examines the therapeutic strategies targeting the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis,along with the regenerative and repair mechanisms linking the axis to spinal cord injury.Additionally,we summarize the upstream and downstream inflammatory signaling pathways associated with spinal cord injury and the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review primarily elaborates on therapeutic strategies that target the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the latest progress of research on antagonistic drugs,along with the approaches used to exploit new therapeutic targets within the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis and the development of targeted drugs.Nevertheless,there are presently no clinical studies relating to spinal cord injury that are focusing on the C-C motif chemokine ligand 2/C-C motif chemokine receptor 2 axis.This review aims to provide new ideas and therapeutic strategies for the future treatment of spinal cord injury.
文摘The presented research illustrates the applicability and productiveness of the systematic literature review methodology, a non-empirical methodology in the geological sciences, particularly volcanology. The systematic literature review methodology is a replicable, rigorous, and transparent methodology for synthesizing existing literature to answer questions on a specific topic. The synthesis allows for knowledge consolidation, such as identifying knowledge gaps. In our illustration of this methodology, we focused on the expanding knowledge about the magma pathway at Mount Cameroon, one of Africa’s active volcanoes. Our synthesis of the relevant international geoscience research literature is based on the framework of knowledge about the magma pathway beneath a typical basaltic volcano. The framework has three primary components: magma supply, storage, and transport to erupting vents. Across these components is a total of twelve secondary components. The result is a previously non-existent and fragmented overall understanding of the magma pathway at Mount Cameroon. The gaps in the understanding (such as in the magma supply rates, timescales of chamber processes, and magma ascent rates) may be addressed in future research. Another key implication of the presented research lies in the proof of concept of the systematic literature review methodology as an applicable qualitative research methodology in the study of volcanoes.
基金supported by the Program for Changjiang Scholars of the Ministry of Education of the People’s Republic of China (No. T2016088)the National Natural Science Foundation for Distinguished Young Scholars (No. 81725021)+4 种基金the National Key R&D Program of China (No. 2021YFA0910500)the Science and Technology Major Project of Hubei Province (No.2021ACA012)the Innovative Research Groups of the National Natural Science Foundation of China (No. 81721005)the Academic Frontier Youth Team of HUST (No. 2017QYTD19)the Fundamental Research Funds for the Central Universities (No.2172019kfy XJJS166)
文摘Cancer represents a significant disease that profoundly impacts human health and longevity.Projections indicate a 47%increase in the global cancer burden by 2040 compared to 2020,accompanied by a further rise in the associated economic burden.Consequently,there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer.Natural products(NPs)play a crucial role in the identification and development of anticancer therapeutics.This study identified ustusolate E(UE)and its analog 11α-hydroxy-ustusolate E(HUE)from strain Aspergillus calidoustus TJ403-EL05,and examined their antitumor activities and mechanisms of action.The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS(human gastric cancer cells)and 786-O(human renal clear cell carcinoma cells),induced irreversible DNA damage,blocked the cell cycle at the G_(2)/M phase,and further induced apoptosis in tumor cells.To the best of the authors’knowledge,this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms.The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.
基金supported by the National Natural Science Foundation of China(Nos.U19A2044,42105132,42030609,and 41975037)the National Key Research and Development Programof China(No.2022YFC3700303).
文摘Extreme ozone pollution events(EOPEs)are associated with synoptic weather patterns(SWPs)and pose severe health and ecological risks.However,a systematic investigation of themeteorological causes,transport pathways,and source contributions to historical EOPEs is still lacking.In this paper,the K-means clustering method is applied to identify six dominant SWPs during the warm season in the Yangtze River Delta(YRD)region from 2016 to 2022.It provides an integrated analysis of the meteorological factors affecting ozone pollution in Hefei under different SWPs.Using the WRF-FLEXPART model,the transport pathways(TPPs)and geographical sources of the near-surface air masses in Hefei during EOPEs are investigated.The results reveal that Hefei experienced the highest ozone concentration(134.77±42.82μg/m^(3)),exceedance frequency(46 days(23.23%)),and proportion of EOPEs(21 instances,47.7%)under the control of peripheral subsidence of typhoon(Type 5).Regional southeast winds correlated with the ozone pollution in Hefei.During EOPEs,a high boundary layer height,solar radiation,and temperature;lowhumidity and cloud cover;and pronounced subsidence airflow occurred over Hefei and the broader YRD region.The East-South(E_S)patterns exhibited the highest frequency(28 instances,65.11%).Regarding the TPPs and geographical sources of the near-surface air masses during historical EOPEs.The YRD was the main source for land-originating air masses under E_S patterns(50.28%),with Hefei,southern Anhui,southern Jiangsu,and northern Zhejiang being key contributors.These findings can help improve ozone pollution early warning and control mechanisms at urban and regional scales.
基金supported by the National Natural Science Foundation of China(Grant No.32170738)the National Medical Research Council of Singapore(Grant No.NMRC/CBRG/0013/2012).
文摘Gastric cancer(GC)is a prevalent and devastating disease with a poor prognosis.The lack of biomarkers for early detection and effective targeted therapeutics for GC patients represents two major challenges.Through isobaric tags for relative and absolute quantitation(iTRAQ)coupled with liquid chromatography-tandem mass spectrometry(LC-MS/MS)phosphoproteomic analysis of 14 GC and gastric epithelial cell lines,we discovered the discoidin domain receptor tyrosine kinase 1(DDR1)as a top potential drug target out of 40 tyrosine kinases detected along with over 1000 phosphoproteins profiled.The DDR1 protein and mRNA levels were upregulated in GC cells concurrent with DDR1 gene amplification.Immunohistochemistry staining of more than 200 clinical samples revealed that DDR1 was overexpressed in approximately 41%and 48%of the intestinal and diffuse types of GC cases,respectively,compared with only 3.5%in normal tissues.Higher DDR1 expression was associated with poor prognosis.In cellular models,DDR1 overexpression led to accelerated proliferation,invasion,and malignant transformation,putatively via inhibition of the Hippo pathway and consequent activation of YAP-TEAD target gene expression.Notably,DDR1-overexpressing GC cells exhibited high vulnerability to selective DDR1 inhibitors.The present study provides preclinical support for the application of DDR1-selective inhibitors in DDR1-overexpressing GC.
基金supported by the Natural Science Basic Research Program of Shaanxi Province(No.2023-JC-JQ-36).
文摘Minocycline has been widely used in clinical treatment and its residues were considered to have environmental safety risks due to complex chemical structure.Therefore,it is necessary to find an efficient and environmentally friendly method to remove minocycline from the environment.This study screened and isolated a minocycline degrading strain DM13 from the activated sludge for municipal sewage pipeline,and optimized the biodegradation of minocycline by DM13 under various environmental conditions.The maximum biodegradation efficiency of 50 mg/L minocycline reached 93%at 72 h with the temperature of 30℃,the initial pH of 7.0,and the inoculation rate of 3%.Two potential biotransformation pathways were proposed,including deamination,demethylation,and decarbonylation.The acute toxicity assessment showed that the biotransformation products of minocycline had lower toxicity than the parent compound.In addition,the first-generation tetracycline antibiotics could be removed,suggesting that strain DM13 has the potential for application in treating antibiotic wastewater.
基金financially supporting this work through the Large Research Group Project under Grant no.R.G.P.2/509/45
文摘Polyphenols,a diverse group of naturally occurring compounds found in plants,have garnered significant attention for their potential therapeutic properties in treating neurodegenerative diseases(NDs).The Wnt/β-catenin(WβC)signaling pathway,a crucial player in neurogenesis,neuronal survival,and synaptic plasticity,is involved in several cellular mechanisms related to NDs.Dysregulation of this pathway is a hallmark in the development of various NDs.This study explores multiple polyphenolic compounds,such as flavonoids,stilbenes,lignans,and phenolic acids,and their potential to protect the nervous system.It provides a comprehensive analysis of their effects on the WβC pathway,elucidating their modes of action.The study highlights the dual function of polyphenols in regulating and protecting the nervous system,providing reassurance about the research benefits.This review provides a comprehensive analysis of the results obtained from both in vitro studies and in vivo research,shedding light on how these substances influence the various components of the pathway.The focus is mainly on the molecular mechanisms that allow polyphenols to reduce oxidative stress,inflammation,and apoptotic processes,ultimately improving the function and survival of neurons.This study aims to offer a thorough understanding of the potential of polyphenols in targeting the WβC signaling pathway,which could lead to the development of innovative therapeutic options for NDs.
基金Supported by Xi’an Science and Technology Plan Project,No.23YXYJ0162Shaanxi Province Traditional Chinese Medicine Research and Innovation Talent Plan Project,No.TZKN-CXRC-16+2 种基金Project of Shaanxi Administration of Traditional Chinese Medicine,No.SZYKJCYC-2025-JC-010Shaanxi Province Key Research and Development Plan Project-Social Development Field,No.S2025-YF-YBSF-0391the Science and Technology Innovation Cultivation Program of Longhua Hospital affiliated to Shanghai University of Chinese Medicine,No.YD202220。
文摘BACKGROUND Excessive endoplasmic reticulum(ER)stress in intestinal epithelial cells can lead to damage to the intestinal mucosal barrier,activate the signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa B(NF-κB)signaling pathway,and exacerbate the inflammatory response,thus participating in the pathogenesis of ulcerative colitis(UC).Mesalazine is a commonly used drug in the clinical treatment of UC.However,further studies are needed to determine whether mesalazine regulates the ER stress of intestinal epithelial cells,downregulates the STAT3/NF-κB pathway to play a role in the treatment of UC.AIM To study the therapeutic effects of mesalazine on spontaneous colitis in interleukin-10(IL-10)-/-mice.METHODS The 24-week-old IL-10-/-mice with spontaneous colitis were divided into the model group and the 5-amino salicylic acid group.Littermates of wild-type mice of the same age group served as the control.There were eight mice in each group,four males and four females.The severity of symptoms of spontaneous colitis in IL-10-/-mice was assessed using disease activity index scores.On day 15,the mice were sacrificed.The colon length was measured,and the histopathological changes and ultrastructure of colonic epithelial cells were detected.The protein expressions of STAT3,p-STAT3,NF-κB,IκB,p-IκB,and glucoseregulated protein 78 were identified using Western blotting.The STAT3 and NF-κB mRNA expressions were identified using real-time polymerase chain reaction.The glucose-regulated protein 78 and C/EBP homologous protein expressions in colon sections were detected using immunofluorescence.RESULTS Mesalazine reduced the symptoms of spontaneous colitis in IL-10 knockout mice and the histopathological damage of colonic tissues,and alleviated the ER stress in epithelial cells of colitis mice.Western blotting and quantitative real-time polymerase chain reaction results showed that the STAT3/NF-κB pathway in the colon tissue of model mice was activated,suggesting that this pathway was involved in the pathogenesis of UC and might become a potential therapeutic target.Mesalazine could down-regulate the protein expressions of p-STAT3,NF-κB and p-IκB,and down-regulate the mRNA expression of STAT3 and NF-κB.CONCLUSION Mesalazine may play a protective role in UC by reducing ER stress by regulating the STAT3/NF-κB signaling pathway.
基金The Andor dragonfly Spinning Disk microscope in the CCI was funded by the BBSRC(BB/R01390X/1)This work was supported by the ministry of education of the Kingdom of Saudi Arabia(to M.Alhashmi)+6 种基金Libyan Ministry of Higher Education and Scientific Research and ECMage(to A.M.E.Gremida)Qatar National Research Fund(to N.A.Al-Maslamani)European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement(860635 to M.Antonaci and A.Kerr)BBSRC Grants(BB/T00715X/1 to S.K.Maharana and G.N.WheelerBB/X000907/1 to D.A.Turner)Versus Arthritis Career Development Fellowship(21447 to K.Yamamoto)Versus Arthritis Bridging Fellowship(23137 to K.Yamamoto).
文摘Low-density lipoprotein receptor-related protein 1(LRP1)is a multifunctional endocytic receptor whose dysfunction is linked to developmental dysplasia of the hip,osteoporosis and osteoarthritis.Our work addresses the critical question of how these skeletal pathologies emerge.Here,we show the abundant expression of LRP1 in skeletal progenitor cells at mouse embryonic stage E10.5 and onwards,especially in the perichondrium,the stem cell layer surrounding developing limbs essential for bone formation.Lrp1 deficiency in these stem cells causes joint fusion,malformation of cartilage/bone template and markedly delayed or lack of primary ossification.
基金supported by the National Key Research and Development Program of China(No.2019YFC1712100)the National Natural Science Foundation of China(No.82105017)。
文摘Objective:The occurrence and development of atrial fibrillation(AF)are influenced by the autonomic nervous system and inflammation.Acupuncture is an effective treatment for AF.This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.Methods:Male Sprague-Dawley rats(n=130)were randomly divided into blank control(Con),sham operation(Sham),AF,and acupuncture treatment(Acu)groups.A paroxysmal AF model was established by rapid atrial pacing through the jugular vein.Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint(PC6)for 20 min daily for seven days.The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture.The AF induction rate,AF duration,cardiac electrophysiological parameters,and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals.After the intervention,the rats were euthanized,and atrial morphology was assessed using haematoxylin and eosin staining.The expression of macrophage F4/80 antigen(F4/80)and cluster of differentiation(CD)86 in atrial myocardial tissue was detected using immunohistochemistry,immunofluorescence and flow cytometry.The expression levels or contents of interleukin(IL)-1β,IL-6,tumor necrosis factor-a(TNF-a),a7 nicotinic acetylcholine receptor(a7nAChR),phosphorylated Janus kinase 2(p-JAK2),and phosphorylated signal transducer and activator of transcription 3(p-STAT3)in atrial myocardial tissue were detected using Western blotting,reverse transcription-quantitative polymerase chain reaction,or enzyme-linked immunosorbent assay.The role of a7nAChR in acupuncture treatment was verified by intraperitoneal injection of the a7nAChR antagonist methyllycaconitine(MLA).Results:Compared with the AF group,acupuncture significantly reduced AF duration and induction rate,improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance.It also decreased the pro-inflammatory M1 macrophage proportion,alleviating myocardial injury and infiltration.MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect.Results suggest that acupuncture triggers the a7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.Conclusion:Acupuncture significantly reduced the AF induction rate,shortened AF duration,improved cardiac electrophysiological parameters,enhanced vagus nerve activity,and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF.
基金financially supported by the National Natural Science Foundation of China(Grants 22225901,21975237 and 51702312)the Fundamental Research Funds for the Central Universities(Grant WK2340000101)+5 种基金the USTC Research Funds of the Double First-Class Initiative(Grant YD2340002007 and YD9990002017)the Open Funds of the State Key Laboratory of Rare Earth Resource Utilization(Grant RERU2022007)the China Postdoctoral Science Foundation(Grants 2023M733371,2024M750006 and 2023T160617)Postdoctoral Fellowship Program(Grade C)of China Postdoctoral Science Foundation(GZC20230008)the Natural Science Foundation Youth Project of Anhui Province(2408085QB065)the Postdoctoral Research Funding Project of Anhui Province(2023B727)。
文摘The electrochemical reduction of carbon dioxide(CO_(2))into value-added chemicals and fuels has been extensively studied as a promising strategy for mitigating environmental issues and achieving sustainable energy conversion.Substantial efforts have been made to improve the understanding of CO_(2)reduction reaction(CO_(2)RR)mechanisms by computational and spectroscopic studies.An in-depth understanding of CO_(2)RR mechanism can provide the guidance and criteria for designing high-efficiency catalysts,and hence,steering CO_(2)RR to desired products.This review systematically discusses the formation mechanisms and reaction pathways of various CO_(2)RR products,including C_(1)products(CO,HCOOH,and CH_(4)),C_(2)products(C_(2)H_(4),C_(2)H_(5)OH,and CH_(3)COOH),and C_(3+)products(C_(3)H_(6),C_(3)H_(7)OH,and others).The reaction pathways are elucidated by analyzing the adsorption behavior,energy barriers,and intermediate coupling steps involved in the generation of each product.Particular emphasis is placed on the key intermediates,such as^(*)OCHO,^(*)COOH,^(*)CO,^(*)OCCOH,and^(*)CCO,which play crucial roles in determining the product selectivity.The effects of catalyst composition,morphology,and electronic structure on the adsorption and activation of these intermediates are also discussed.Moreover,advanced characterization techniques,including in-situ spectroscopy and isotopic labeling experiments,are highlighted for their contributions to unraveling the reaction mechanisms.The review aims to provide critical insights to reveal the activity-determining para meters and underlying CO_(2)RR mechanisms,which will guide the rational design of next-generation electrocatalysts for selective CO^(2)RR towards high-value products.
基金supported by the Natural Science Foundation of Yunnan Province,No.202401AS070086(to ZW)the National Key Research and Development Program of China,No.2018YFA0801403(to ZW)+1 种基金Yunnan Science and Technology Talent and Platform Plan,No.202105AC160041(to ZW)the Natural Science Foundation of China,No.31960120(to ZW)。
文摘Traumatic brain injury can be categorized into primary and secondary injuries.Secondary injuries are the main cause of disability following traumatic brain injury,which involves a complex multicellular cascade.Microglia play an important role in secondary injury and can be activated in response to traumatic brain injury.In this article,we review the origin and classification of microglia as well as the dynamic changes of microglia in traumatic brain injury.We also clarify the microglial polarization pathways and the therapeutic drugs targeting activated microglia.We found that regulating the signaling pathways involved in pro-inflammatory and anti-inflammatory microglia,such as the Toll-like receptor 4/nuclear factor-kappa B,mitogen-activated protein kinase,Janus kinase/signal transducer and activator of transcription,phosphoinositide 3-kinase/protein kinase B,Notch,and high mobility group box 1 pathways,can alleviate the inflammatory response triggered by microglia in traumatic brain injury,thereby exerting neuroprotective effects.We also reviewed the strategies developed on the basis of these pathways,such as drug and cell replacement therapies.Drugs that modulate inflammatory factors,such as rosuvastatin,have been shown to promote the polarization of antiinflammatory microglia and reduce the inflammatory response caused by traumatic brain injury.Mesenchymal stem cells possess anti-inflammatory properties,and clinical studies have confirmed their significant efficacy and safety in patients with traumatic brain injury.Additionally,advancements in mesenchymal stem cell-delivery methods—such as combinations of novel biomaterials,genetic engineering,and mesenchymal stem cell exosome therapy—have greatly enhanced the efficiency and therapeutic effects of mesenchymal stem cells in animal models.However,numerous challenges in the application of drug and mesenchymal stem cell treatment strategies remain to be addressed.In the future,new technologies,such as single-cell RNA sequencing and transcriptome analysis,can facilitate further experimental studies.Moreover,research involving non-human primates can help translate these treatment strategies to clinical practice.
