The baryon spectrum and the baryon couplings are two of the most important issues in hadronic physics andthey are attracting much attention. Both on the experimental and theoretical sides, the nucleon excited states b...The baryon spectrum and the baryon couplings are two of the most important issues in hadronic physics andthey are attracting much attention. Both on the experimental and theoretical sides, the nucleon excited states below2.0 GeV have been extensively studied[1]. However, the current information for the properties of states around orabove 2.0 GeV is scarce. On the other hand, in this energy region, many theoretical approaches have predictedmissing N states, which have not been so far observed. Hence, the study of the possible role played by the 2.0GeV region nucleon resonances in the available accurate data is timely and could shed light into the complicateddynamics that governs the high excited nucleon spectrum.展开更多
Chrome-molybdenum steel(2·1/4Cr1Mo) is one of the main products of steam generation.The adsorption behaviors of radioactive fission products on2·1/4Cr1Mo surface are critical in the analysis of HTR-PM.Here,t...Chrome-molybdenum steel(2·1/4Cr1Mo) is one of the main products of steam generation.The adsorption behaviors of radioactive fission products on2·1/4Cr1Mo surface are critical in the analysis of HTR-PM.Here,the adsorption behavior of cesium,strontium,silver and iodine on 2·1/4Cr1Mo was investigated with first-principle calculations that the Ag and I atoms prefer to be adsorbed at the square hollow site of the face-centered cubic iron cell with a binding energy of about 1 and 3 eV,respectively.In contrast,Cs and Sr atoms are not adsorbed on the surface of the 2·1/4Cr1Mo.These results are again confirmed via analysis of charge density differences and the densities of state.Furthermore,the adsorption rates of these fission products show that only I and Ag have significant adsorption on the metal substrate.These adsorption results explain the amount of adsorbed radionuclides for an evaluation of nuclear safety in HTR-PM.These micro-pictures of the interaction between fission products and materials are a new and useful way to analyze the source term.展开更多
We report the multiplicity dependence of charged particle production for the n~±, K~±, p, , and ? mesons at |y|<1:0 in p + p collisions at s^(1/2) = 200 GeV from a PYTHIA simulation. The impact of multipl...We report the multiplicity dependence of charged particle production for the n~±, K~±, p, , and ? mesons at |y|<1:0 in p + p collisions at s^(1/2) = 200 GeV from a PYTHIA simulation. The impact of multiple parton interactions and gluon contributions is studied and found to be a possible source of the splitting of the particle yields as a function of p_T with respect to the multiplicity. No obvious particle species dependence of the splitting is observed.The multiplicity dependence of the ratios Kˉ/πˉ, K^+/π^+,/πˉ, p/π^+, and K_s^0 at mid-rapidity in p+ p collisions is found to follow a tendency similar to that in Au t Au collisions at (s_(NN))^(1/2) = 200 GeV at the Relativistic Heavy Ion Collider, indicating similar underlying initial production mechanisms despite the differences in the initial colliding systems.展开更多
The easy acidification and high hydrogen sulfide （H2S） production during anaerobic digestion of macroalgae limited its application in biomethane production. In order to investigate the effects of ceramsite on methan...The easy acidification and high hydrogen sulfide （H2S） production during anaerobic digestion of macroalgae limited its application in biomethane production. In order to investigate the effects of ceramsite on methane and HzS productions during anaerobic digestion of macroalgae, batch experiments ofMacrocystis pyrifera were carried out. Four groups named C0, C1, C2 and C3 added with 0, 1.5, 3.0 and 4.5 g/g substrate of ceramsite, respectively, were studied and compared. The highest cumulative methane yield of 286.3 mL/g substrate is obtained in C2, which is 40.11% higher than that of CO. The cumulative HzS yields of C1, C2 and C3 are 32.67%, 44.66% and 53.21% lower than that of CO, respectively. Results indicate that ceramsite addition permits higher methane yields, shorter lag-phase time and lower HzS yields during anaerobic digestion of Macrocystispyrifera.展开更多
The author uses system analysis to provide system thinkings of the deepening reform of the management of defence science, technology and industry (DSTI) and investigate the system definition of DSTI, the system reform...The author uses system analysis to provide system thinkings of the deepening reform of the management of defence science, technology and industry (DSTI) and investigate the system definition of DSTI, the system reform target, system operational mechanism, institutional structure, coordination and control functions and the orientation of conversion in China.展开更多
Tendinopathy is a challenging complication observed in patients with diabetes mellitus.Tendinopathy usually leads to chronic pain,limited joint motion,and even ruptured tendons.Imaging and histological analyses have r...Tendinopathy is a challenging complication observed in patients with diabetes mellitus.Tendinopathy usually leads to chronic pain,limited joint motion,and even ruptured tendons.Imaging and histological analyses have revealed pathological changes in various tendons of patients with diabetes,including disorganized arrangement of collagen fibers,microtears,calcium nodules,and advanced glycation end product(AGE)deposition.Tendon-derived stem/progenitor cells(TSPCs)were found to maintain hemostasis and to participate in the reversal of tendinopathy.We also discovered the aberrant osteochondrogenesis of TSPCs in vitro.However,the relationship between AGEs and TSPCs in diabetic tendinopathy and the underlying mechanism remain unclear.In this review,we summarize the current findings in this field and hypothesize that AGEs could alter the properties of tendons in patients with diabetes by regulating the proliferation and differentiation of TSPCs in vivo.展开更多
We investigate the cold nuclear matter(CNM) effects on isolated prompt photon and isolated prompt photon associated jet productions in nuclear collisions at the NLO accuracy by using the EPS09 NLO nuclear parton distr...We investigate the cold nuclear matter(CNM) effects on isolated prompt photon and isolated prompt photon associated jet productions in nuclear collisions at the NLO accuracy by using the EPS09 NLO nuclear parton distribution functions and their error sets.Nuclear modification factors of isolated prompt photon and isolated prompt photon+jet productions due to CNM effects in p+A and A+A reactions at the RHIC and the LHC are provided with varying rapidity and transverse momentum of the final state photon.It is shown that the CNM effects on isolated prompt photon and photon+jet are modest,which give a small enhancement at low pT region and a more obvious suppression at large pT at central rapidity.At forward rapidity a pronounced suppression of γ as well as γ+jet is always observed.展开更多
Livestock husbandry plays a very important role in rural areas of Cambodia. Farmers mostly have complained about the declining revenue from livestock production which supports their livelihood. Therefore, the study ai...Livestock husbandry plays a very important role in rural areas of Cambodia. Farmers mostly have complained about the declining revenue from livestock production which supports their livelihood. Therefore, the study aimed at investigating the potentials and constraints of smallholder livestock productions in Battambang province. Primary and secondary data were collected to meet the objectives. Data were collected interviewing 204 households. Some of the advantages of the Cambodia livestock subsector are the increasing market demand: increasing domestic market for livestock and increasing demand from neighboring countries (especially cattle);the rich source of manure and other agricultural input such as transportation means, ploughing etc. More so, there is high expectation of the farmers experiencing increase in production since more supports are provided by both governmental and non-governmental organizations. On the other hand, the subsector witnesses some constraints including the low level of education of the livestock farmers, erratic market prices as a result of too many middlemen, local breed with low productivity and traditional management system still dominates the sub- sector. Scarcity of abled labor and seasonal cost is also one of the factors impeding the subsector to reaching it potential. This study suggests that to reach full potential in the livestock sector of Battambang of Cambodia, the government needs to address the infrastructural problems and private sector needs to be encouraged to invest in the sector in livestock input industries.展开更多
Production of bee products using standards of Modern technology requires high specialization and high productivity of labor adequate facilities and equipment, and coordination of natural bee potential with production ...Production of bee products using standards of Modern technology requires high specialization and high productivity of labor adequate facilities and equipment, and coordination of natural bee potential with production characteristics of the wider region. Effectively beekeeping today means using several pastures per year with a yield of 50-60 kg per hive. Mobile beekeeping is the only way to achieve high yields of production and it has considerable advantage over stationary one which is less rentable. Mobile beekeeping require higher investments and labor but with good climate and ecological conditions, one can achieve several times higher income than in stationary beekeeping. Some of the success in mobile beekeeping depends of the selection of hives. The hives must be designed to give the bees the best environment for work and development to be most efficient. Data was collected from 57 beekeepers that live in the district. Data analysis was conducted by using standard statistical and economic processes. Criteria for a recommended for the proposed beekeeping model were incomes and profit per hive. For effective beekeeping and production of bee products, especially honey, beekeeper must have adequate equipment and a good bee hives. Beekeeper must have transportation and additional equipment because their movement depends season on the season and distance to pasture.展开更多
The transverse single-spin asymmetry forρ^(0) production in semi-inclusive deep inelastic scattering was recently reported by the COMPASS Collaboration.Using the Sivers function extracted from pion and kaon productio...The transverse single-spin asymmetry forρ^(0) production in semi-inclusive deep inelastic scattering was recently reported by the COMPASS Collaboration.Using the Sivers function extracted from pion and kaon productions,we perform a calculation of the Sivers asymmetry within the transverse momentum-dependent factorization.Our results are consistent with the COMPASS data,supporting the universality of the Sivers function in the semi-inclusive deep inelastic scattering process for different final-state hadrons within current experimental uncertainties.While different parametrizations of the Sivers function from global analyses allow describing the data equally well,we obtain very different predictions on the Sivers asymmetry ofρand K^(*)productions at electron-ion colliders,which therefore are expected to provide further constraints.展开更多
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
The rich resources and unique environment of the Moon make it an ideal location for human expansion and the utilization of extraterrestrial resources.Oxygen,crucial for supporting human life on the Moon,can be extract...The rich resources and unique environment of the Moon make it an ideal location for human expansion and the utilization of extraterrestrial resources.Oxygen,crucial for supporting human life on the Moon,can be extracted from lunar regolith,which is highly rich in oxygen and contains polymetallic oxides.This oxygen and metal extraction can be achieved using existing metallurgical techniques.Furthermore,the ample reserves of water ice on the Moon offer another means for oxygen production.This paper offers a detailed overview of the leading technologies for achieving oxygen production on the Moon,drawing from an analysis of lunar resources and environmental conditions.It delves into the principles,processes,advantages,and drawbacks of water-ice electrolysis,two-step oxygen production from lunar regolith,and one-step oxygen production from lunar regolith.The two-step methods involve hydrogen reduction,carbothermal reduction,and hydrometallurgy,while the one-step methods encompass fluorination/chlorination,high-temperature decomposition,molten salt electrolysis,and molten regolith electrolysis(MOE).Following a thorough comparison of raw materials,equipment,technology,and economic viability,MOE is identified as the most promising approach for future in-situ oxygen production on the Moon.Considering the corrosion characteristics of molten lunar regolith at high temperatures,along with the Moon's low-gravity environment,the development of inexpensive and stable inert anodes and electrolysis devices that can easily collect oxygen is critical for promoting MOE technology on the Moon.This review significantly contributes to our understanding of in-situ oxygen production technologies on the Moon and supports upcoming lunar exploration initiatives.展开更多
BACKGROUND Gastric cancer(GC)is a prevalent malignancy with a substantial health burden and high mortality rate,despite advances in prevention,early detection,and treatment.Compared with the global average,Asia,notabl...BACKGROUND Gastric cancer(GC)is a prevalent malignancy with a substantial health burden and high mortality rate,despite advances in prevention,early detection,and treatment.Compared with the global average,Asia,notably China,reports disproportionately high GC incidences.The disease often progresses asymptoma-tically in the early stages,leading to delayed diagnosis and compromised out-comes.Thus,it is crucial to identify early diagnostic biomarkers and enhance treatment strategies to improve patient outcomes and reduce mortality.METHODS Retrospectively analyzed the clinical data of 148 patients with GC treated at the Civil Aviation Shanghai Hospital between December 2022 and December 2023.The associations of coagulation indices-partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen,fibrinogen degradation products(FDP),fasting blood glucose,and D-dimer(D-D)with TNM stage and distant metastasis were examined.RESULTS Prolongation of APTT,PT,and TT was significantly correlated with the GC TNM stage.Hence,abnormal coagulation system activation was closely related to disease progression.Elevated FDP and D-D were significantly associated with distant metastasis in GC(P<0.05),suggesting that increased fibrinolytic activity contributes to increased metastatic risk.CONCLUSION Our Results reveal coagulation indices,FDPs as GC biomarkers,reflecting abnormal coagulation/fibrinolysis,aiding disease progression,metastasis prediction,and helping clinicians assess thrombotic risk for early intervention and personalized treatment plans.展开更多
Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation ...Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa,in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis(Phase I)to gastric precancerous lesions(Phase II)and finally to GC(Phase III).Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa.Intervening in early gastric mucosal lesions,i.e.,Phases I and II,will be the key strategy to prevent and treat GC.Natural products(NPs)have been an important source for drug development due to abundant sources,tremendous safety,and multiple pharmacodynamic mechanisms.This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis.In Phase I,NPs modulate Helicobacter pylori urease activity,motility,adhesion,virulence factors,and drug resistance,thereby inhibiting H.pylori-induced gastric mucosal inflammation and oxidative stress,and facilitating ulcer healing.In Phase II,NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle,apoptosis,autophagy,and angiogenesis to reverse gastric precancerous lesions.In Phase III,NPs suppress cell proliferation,migration,invasion,angiogenesis,and cancer stem cells,induce apoptosis and autophagy,and enhance chemotherapeutic drug sensitivity for the treatment of GC.In contrast to existing work,we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development,providing new ideas for gastric cancer prevention,treatment,and drug development.展开更多
Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the ...Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the present study,an innovative natural product virtual screening-interaction-phenotype(NP-VIP)strategy that integrates virtual screening,chemical proteomics,and metabolomics to identify and validate the bioactive targets of NPs.This approach reduces false positive results and enhances the efficiency of target identification.Salvia miltiorrhiza(SM),a herb with recognized therapeutic potential against ischemic stroke(IS),was used to illustrate the workflow.Utilizing virtual screening,chemical proteomics,and metabolomics,potential therapeutic targets for SM in the IS treatment were identified,totaling 29,100,and 78,respectively.Further analysis via the NP-VIP strategy highlighted five high-confidence targets,including poly[ADP-ribose]polymerase 1(PARP1),signal transducer and activator of transcription 3(STAT3),amyloid precursor protein(APP),glutamate-ammonia ligase(GLUL),and glutamate decarboxylase 67(GAD67).These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM.The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research,proposing a comprehensive approach that could be adapted for broader pharmacological explorations.展开更多
Developing deep fragmented soft coalbed methane(CBM)can significantly enhance domestic natural gas supplies,reduce reliance on imported energy,and bolster national energy security.This manuscript provides a comprehens...Developing deep fragmented soft coalbed methane(CBM)can significantly enhance domestic natural gas supplies,reduce reliance on imported energy,and bolster national energy security.This manuscript provides a comprehensive review of commonly employed coalbed methane extraction technologies.It then delves into several critical issues in the current stage of CBM exploration and development in China,including the compatibility of existing technologies with CBM reservoirs,the characteristics and occurrence states of CBM reservoirs,critical desorption pressure,and gas generation mechanisms.Our research indicates that current CBM exploration and development technologies in China have reached an internationally advanced level,yet the industry is facing unprecedented challenges.Despite progress in low-permeability,high-value coal seams,significant breakthroughs have not been achieved in exploring other types of coal seams.For different coal reservoirs,integrated extraction technologies have been developed,such as surface pre-depressurisation and segmented hydraulic fracturing of coal seam roof strata.Additionally,techniques like large-scale volume fracturing in horizontal wells have been established,significantly enhancing reservoir stimulation effects and coalbed methane recovery rates.However,all of these technologies are fundamentally based on permeation.These technologies lack direct methods aimed at enhancing the diffusion rate of CBM,thereby failing to fully reflect the unique characteristics of CBM.Current CBM exploration and development theories and technologies are not universally applicable to all coal seams.They do not adequately account for the predominantly adsorbed state of CBM,and the complex and variable gas generation mechanisms further constrain CBM development in China.Finally,continuous exploration of new deep CBM exploration technologies is necessary.Integrating more effective reservoir stimulation technologies is essential to enhance technical adaptability concerning CBM reservoir characteristics,gas occurrence states,and gas generation mechanisms,ultimately achieving efficient CBM development.We conclude that while China possesses a substantial foundation of deep fractured CBM resources,industry development is constrained and requires continuous exploration of new CBM exploration and development technologies to utilize these resources effectively.展开更多
Natural products,with their remarkable structural and biological diversity,have historically served as a vital bridge between chemistry,the life sciences,and medicine.They not only provide essential scaffolds for drug...Natural products,with their remarkable structural and biological diversity,have historically served as a vital bridge between chemistry,the life sciences,and medicine.They not only provide essential scaffolds for drug discovery but also inspire innovative strategies in drug development.The biomimetic synthesis of natural products employs principles from biomimicry,applying inspiration from biogenetic processes to design synthetic strategies that mimic biosynthetic processes.Biomimetic synthesis is a highly efficient approach in synthetic chemistry,as it addresses critical challenges in the synthesis of structurally complex natural products with significant biological and medicinal importance.It has gained widespread attention from researchers in chemistry,biology,pharmacy,and related fields,underscoring its interdisciplinary impact.In this perspective,we present recent advances and challenges in the biomimetic synthesis of natural products,along with the significance and prospects of this field,highlighting the transformative potential of biomimetic synthesis strategies for both chemical and biosynthetic approaches to natural product synthesis in the pursuit of novel therapeutic agents.展开更多
1.Introduction As China’s first floating production platform in ultra-deepwater,the“Deep Sea No.1”energy station is a milestone in China’s deepwater resource utilization.The energy station is located in the LS17-2...1.Introduction As China’s first floating production platform in ultra-deepwater,the“Deep Sea No.1”energy station is a milestone in China’s deepwater resource utilization.The energy station is located in the LS17-2 gas field,150 km off the southeast coast of Hainan Island,China.It is a semi-submersible platform(Fig.1)with a displacement of 101 thousand tonnes and an operational draft of 35 to 40 m.The platform is permanently moored in 1422 m water by 16 chain-polyester-chain mooring lines in a 4×4 pattern,and six steel catenary risers(SCRs)are attached to the platform.It is the world’s first and only semi-submersible platform with the function of condensate storage,so it can be regarded as a floating production storage and offloading(FPSO)unit.With the ability to produce 3 billion m3 of natural gas each year(enough for over 10 million families),the Deep Sea No.1 energy station is a key step toward China’s energy independence.The LS17-2 gas field,where the Deep Sea No.1 energy station is located,was discovered in 2014.Plans for its development were made in 2015,followed by research and a preliminary design.Deep Sea No.1 went into operation on June 25,2021,and will operate onsite continuously without dry-docking for 30 years.展开更多
OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-perf...OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.展开更多
Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating...Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.展开更多
文摘The baryon spectrum and the baryon couplings are two of the most important issues in hadronic physics andthey are attracting much attention. Both on the experimental and theoretical sides, the nucleon excited states below2.0 GeV have been extensively studied[1]. However, the current information for the properties of states around orabove 2.0 GeV is scarce. On the other hand, in this energy region, many theoretical approaches have predictedmissing N states, which have not been so far observed. Hence, the study of the possible role played by the 2.0GeV region nucleon resonances in the available accurate data is timely and could shed light into the complicateddynamics that governs the high excited nucleon spectrum.
基金supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China(No.ZX06901)
文摘Chrome-molybdenum steel(2·1/4Cr1Mo) is one of the main products of steam generation.The adsorption behaviors of radioactive fission products on2·1/4Cr1Mo surface are critical in the analysis of HTR-PM.Here,the adsorption behavior of cesium,strontium,silver and iodine on 2·1/4Cr1Mo was investigated with first-principle calculations that the Ag and I atoms prefer to be adsorbed at the square hollow site of the face-centered cubic iron cell with a binding energy of about 1 and 3 eV,respectively.In contrast,Cs and Sr atoms are not adsorbed on the surface of the 2·1/4Cr1Mo.These results are again confirmed via analysis of charge density differences and the densities of state.Furthermore,the adsorption rates of these fission products show that only I and Ag have significant adsorption on the metal substrate.These adsorption results explain the amount of adsorbed radionuclides for an evaluation of nuclear safety in HTR-PM.These micro-pictures of the interaction between fission products and materials are a new and useful way to analyze the source term.
基金supported by the Major State Basic Research Development Program in China(No.2014CB845400)the National Natural Science Foundation of China(No.11375184)+2 种基金the Youth Innovation Promotion Association Fund of CAS(No.CX2030040079)the Ministry of Science and Technology(Mo ST)of China(No.2016YFE0104800)the Science and Technological Fund of Anhui Province for Outstanding Youth(No.1808085J02)
文摘We report the multiplicity dependence of charged particle production for the n~±, K~±, p, , and ? mesons at |y|<1:0 in p + p collisions at s^(1/2) = 200 GeV from a PYTHIA simulation. The impact of multiple parton interactions and gluon contributions is studied and found to be a possible source of the splitting of the particle yields as a function of p_T with respect to the multiplicity. No obvious particle species dependence of the splitting is observed.The multiplicity dependence of the ratios Kˉ/πˉ, K^+/π^+,/πˉ, p/π^+, and K_s^0 at mid-rapidity in p+ p collisions is found to follow a tendency similar to that in Au t Au collisions at (s_(NN))^(1/2) = 200 GeV at the Relativistic Heavy Ion Collider, indicating similar underlying initial production mechanisms despite the differences in the initial colliding systems.
基金Project(2014BAC31B01)supported by the National Science&Technology Support during the 12th Five-Year Plan Period,ChinaProjects(2015GSF117016,2015GSF115037)supported by the Key Research&Development Project of Shandong Province,China
文摘The easy acidification and high hydrogen sulfide （H2S） production during anaerobic digestion of macroalgae limited its application in biomethane production. In order to investigate the effects of ceramsite on methane and HzS productions during anaerobic digestion of macroalgae, batch experiments ofMacrocystis pyrifera were carried out. Four groups named C0, C1, C2 and C3 added with 0, 1.5, 3.0 and 4.5 g/g substrate of ceramsite, respectively, were studied and compared. The highest cumulative methane yield of 286.3 mL/g substrate is obtained in C2, which is 40.11% higher than that of CO. The cumulative HzS yields of C1, C2 and C3 are 32.67%, 44.66% and 53.21% lower than that of CO, respectively. Results indicate that ceramsite addition permits higher methane yields, shorter lag-phase time and lower HzS yields during anaerobic digestion of Macrocystispyrifera.
文摘The author uses system analysis to provide system thinkings of the deepening reform of the management of defence science, technology and industry (DSTI) and investigate the system definition of DSTI, the system reform target, system operational mechanism, institutional structure, coordination and control functions and the orientation of conversion in China.
基金National Natural Science Foundation of China,No.81572187 and No.81871812Jiangsu Provincial Medical Talent,The Project of Invigorating Health Care through Science,Technology and Education,No.ZDRCA2016083+2 种基金Natural Science Foundation of Jiangsu Province for Young Scholars,China,No.BK20200398Entrepreneurship and Innovation Program of Jiangsu Province,China,No.1190000054and The Six Projects Sponsoring Talent Summits of Jiangsu Province,China,No.LGY2017099。
文摘Tendinopathy is a challenging complication observed in patients with diabetes mellitus.Tendinopathy usually leads to chronic pain,limited joint motion,and even ruptured tendons.Imaging and histological analyses have revealed pathological changes in various tendons of patients with diabetes,including disorganized arrangement of collagen fibers,microtears,calcium nodules,and advanced glycation end product(AGE)deposition.Tendon-derived stem/progenitor cells(TSPCs)were found to maintain hemostasis and to participate in the reversal of tendinopathy.We also discovered the aberrant osteochondrogenesis of TSPCs in vitro.However,the relationship between AGEs and TSPCs in diabetic tendinopathy and the underlying mechanism remain unclear.In this review,we summarize the current findings in this field and hypothesize that AGEs could alter the properties of tendons in patients with diabetes by regulating the proliferation and differentiation of TSPCs in vivo.
基金Supported by the Ministry of Education of China with Project No. NCET-09-0411the National Natural Science Foundation of China with Project Nos. 11075062,11221504+1 种基金the Natural Science Foundation of Hubei Province with Project No. 2010CDA075Self-Determined Research Funds of CCNU
文摘We investigate the cold nuclear matter(CNM) effects on isolated prompt photon and isolated prompt photon associated jet productions in nuclear collisions at the NLO accuracy by using the EPS09 NLO nuclear parton distribution functions and their error sets.Nuclear modification factors of isolated prompt photon and isolated prompt photon+jet productions due to CNM effects in p+A and A+A reactions at the RHIC and the LHC are provided with varying rapidity and transverse momentum of the final state photon.It is shown that the CNM effects on isolated prompt photon and photon+jet are modest,which give a small enhancement at low pT region and a more obvious suppression at large pT at central rapidity.At forward rapidity a pronounced suppression of γ as well as γ+jet is always observed.
文摘Livestock husbandry plays a very important role in rural areas of Cambodia. Farmers mostly have complained about the declining revenue from livestock production which supports their livelihood. Therefore, the study aimed at investigating the potentials and constraints of smallholder livestock productions in Battambang province. Primary and secondary data were collected to meet the objectives. Data were collected interviewing 204 households. Some of the advantages of the Cambodia livestock subsector are the increasing market demand: increasing domestic market for livestock and increasing demand from neighboring countries (especially cattle);the rich source of manure and other agricultural input such as transportation means, ploughing etc. More so, there is high expectation of the farmers experiencing increase in production since more supports are provided by both governmental and non-governmental organizations. On the other hand, the subsector witnesses some constraints including the low level of education of the livestock farmers, erratic market prices as a result of too many middlemen, local breed with low productivity and traditional management system still dominates the sub- sector. Scarcity of abled labor and seasonal cost is also one of the factors impeding the subsector to reaching it potential. This study suggests that to reach full potential in the livestock sector of Battambang of Cambodia, the government needs to address the infrastructural problems and private sector needs to be encouraged to invest in the sector in livestock input industries.
文摘Production of bee products using standards of Modern technology requires high specialization and high productivity of labor adequate facilities and equipment, and coordination of natural bee potential with production characteristics of the wider region. Effectively beekeeping today means using several pastures per year with a yield of 50-60 kg per hive. Mobile beekeeping is the only way to achieve high yields of production and it has considerable advantage over stationary one which is less rentable. Mobile beekeeping require higher investments and labor but with good climate and ecological conditions, one can achieve several times higher income than in stationary beekeeping. Some of the success in mobile beekeeping depends of the selection of hives. The hives must be designed to give the bees the best environment for work and development to be most efficient. Data was collected from 57 beekeepers that live in the district. Data analysis was conducted by using standard statistical and economic processes. Criteria for a recommended for the proposed beekeeping model were incomes and profit per hive. For effective beekeeping and production of bee products, especially honey, beekeeper must have adequate equipment and a good bee hives. Beekeeper must have transportation and additional equipment because their movement depends season on the season and distance to pasture.
基金supported by the National Key R&D Program of China(Grant No.2024YFA1611004)the National Natural Science Foundation of China(Grant Nos.12175117,12475084,and 12321005)the Shandong Province Natural Science Foundation(Grant Nos.ZFJH202303 and ZR2024MA012)。
文摘The transverse single-spin asymmetry forρ^(0) production in semi-inclusive deep inelastic scattering was recently reported by the COMPASS Collaboration.Using the Sivers function extracted from pion and kaon productions,we perform a calculation of the Sivers asymmetry within the transverse momentum-dependent factorization.Our results are consistent with the COMPASS data,supporting the universality of the Sivers function in the semi-inclusive deep inelastic scattering process for different final-state hadrons within current experimental uncertainties.While different parametrizations of the Sivers function from global analyses allow describing the data equally well,we obtain very different predictions on the Sivers asymmetry ofρand K^(*)productions at electron-ion colliders,which therefore are expected to provide further constraints.
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financially supported by the National Natural Science Foundation of China(Nos.52404328,52274412,and 52374418)the China Postdoctoral Science Foundation(No.2024M753248)。
文摘The rich resources and unique environment of the Moon make it an ideal location for human expansion and the utilization of extraterrestrial resources.Oxygen,crucial for supporting human life on the Moon,can be extracted from lunar regolith,which is highly rich in oxygen and contains polymetallic oxides.This oxygen and metal extraction can be achieved using existing metallurgical techniques.Furthermore,the ample reserves of water ice on the Moon offer another means for oxygen production.This paper offers a detailed overview of the leading technologies for achieving oxygen production on the Moon,drawing from an analysis of lunar resources and environmental conditions.It delves into the principles,processes,advantages,and drawbacks of water-ice electrolysis,two-step oxygen production from lunar regolith,and one-step oxygen production from lunar regolith.The two-step methods involve hydrogen reduction,carbothermal reduction,and hydrometallurgy,while the one-step methods encompass fluorination/chlorination,high-temperature decomposition,molten salt electrolysis,and molten regolith electrolysis(MOE).Following a thorough comparison of raw materials,equipment,technology,and economic viability,MOE is identified as the most promising approach for future in-situ oxygen production on the Moon.Considering the corrosion characteristics of molten lunar regolith at high temperatures,along with the Moon's low-gravity environment,the development of inexpensive and stable inert anodes and electrolysis devices that can easily collect oxygen is critical for promoting MOE technology on the Moon.This review significantly contributes to our understanding of in-situ oxygen production technologies on the Moon and supports upcoming lunar exploration initiatives.
文摘BACKGROUND Gastric cancer(GC)is a prevalent malignancy with a substantial health burden and high mortality rate,despite advances in prevention,early detection,and treatment.Compared with the global average,Asia,notably China,reports disproportionately high GC incidences.The disease often progresses asymptoma-tically in the early stages,leading to delayed diagnosis and compromised out-comes.Thus,it is crucial to identify early diagnostic biomarkers and enhance treatment strategies to improve patient outcomes and reduce mortality.METHODS Retrospectively analyzed the clinical data of 148 patients with GC treated at the Civil Aviation Shanghai Hospital between December 2022 and December 2023.The associations of coagulation indices-partial thromboplastin time(APTT),prothrombin time(PT),thrombin time(TT),fibrinogen,fibrinogen degradation products(FDP),fasting blood glucose,and D-dimer(D-D)with TNM stage and distant metastasis were examined.RESULTS Prolongation of APTT,PT,and TT was significantly correlated with the GC TNM stage.Hence,abnormal coagulation system activation was closely related to disease progression.Elevated FDP and D-D were significantly associated with distant metastasis in GC(P<0.05),suggesting that increased fibrinolytic activity contributes to increased metastatic risk.CONCLUSION Our Results reveal coagulation indices,FDPs as GC biomarkers,reflecting abnormal coagulation/fibrinolysis,aiding disease progression,metastasis prediction,and helping clinicians assess thrombotic risk for early intervention and personalized treatment plans.
基金supported by the Chengdu University of Traditional Chinese Medicine"Xinglin Scholars"Program,China(Grant No.:MPRC2023014).
文摘Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa,in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis(Phase I)to gastric precancerous lesions(Phase II)and finally to GC(Phase III).Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa.Intervening in early gastric mucosal lesions,i.e.,Phases I and II,will be the key strategy to prevent and treat GC.Natural products(NPs)have been an important source for drug development due to abundant sources,tremendous safety,and multiple pharmacodynamic mechanisms.This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis.In Phase I,NPs modulate Helicobacter pylori urease activity,motility,adhesion,virulence factors,and drug resistance,thereby inhibiting H.pylori-induced gastric mucosal inflammation and oxidative stress,and facilitating ulcer healing.In Phase II,NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle,apoptosis,autophagy,and angiogenesis to reverse gastric precancerous lesions.In Phase III,NPs suppress cell proliferation,migration,invasion,angiogenesis,and cancer stem cells,induce apoptosis and autophagy,and enhance chemotherapeutic drug sensitivity for the treatment of GC.In contrast to existing work,we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development,providing new ideas for gastric cancer prevention,treatment,and drug development.
基金supported by the National Natural Science Foundations of China(Grant No.:82204584)Liaoning Provincial Science and Technology Projects,China(Project No.:2021JH1/10400055).
文摘Natural products(NPs)have historically been a fundamental source for drug discovery.Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents,and corresponding targets.In the present study,an innovative natural product virtual screening-interaction-phenotype(NP-VIP)strategy that integrates virtual screening,chemical proteomics,and metabolomics to identify and validate the bioactive targets of NPs.This approach reduces false positive results and enhances the efficiency of target identification.Salvia miltiorrhiza(SM),a herb with recognized therapeutic potential against ischemic stroke(IS),was used to illustrate the workflow.Utilizing virtual screening,chemical proteomics,and metabolomics,potential therapeutic targets for SM in the IS treatment were identified,totaling 29,100,and 78,respectively.Further analysis via the NP-VIP strategy highlighted five high-confidence targets,including poly[ADP-ribose]polymerase 1(PARP1),signal transducer and activator of transcription 3(STAT3),amyloid precursor protein(APP),glutamate-ammonia ligase(GLUL),and glutamate decarboxylase 67(GAD67).These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM.The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research,proposing a comprehensive approach that could be adapted for broader pharmacological explorations.
基金supported by the National Natural Science Foundation of China(52074045,52274074)the Science Fund for Distinguished Young Scholars of Chongqing(CSTB2022NSCQ-JQX0028).
文摘Developing deep fragmented soft coalbed methane(CBM)can significantly enhance domestic natural gas supplies,reduce reliance on imported energy,and bolster national energy security.This manuscript provides a comprehensive review of commonly employed coalbed methane extraction technologies.It then delves into several critical issues in the current stage of CBM exploration and development in China,including the compatibility of existing technologies with CBM reservoirs,the characteristics and occurrence states of CBM reservoirs,critical desorption pressure,and gas generation mechanisms.Our research indicates that current CBM exploration and development technologies in China have reached an internationally advanced level,yet the industry is facing unprecedented challenges.Despite progress in low-permeability,high-value coal seams,significant breakthroughs have not been achieved in exploring other types of coal seams.For different coal reservoirs,integrated extraction technologies have been developed,such as surface pre-depressurisation and segmented hydraulic fracturing of coal seam roof strata.Additionally,techniques like large-scale volume fracturing in horizontal wells have been established,significantly enhancing reservoir stimulation effects and coalbed methane recovery rates.However,all of these technologies are fundamentally based on permeation.These technologies lack direct methods aimed at enhancing the diffusion rate of CBM,thereby failing to fully reflect the unique characteristics of CBM.Current CBM exploration and development theories and technologies are not universally applicable to all coal seams.They do not adequately account for the predominantly adsorbed state of CBM,and the complex and variable gas generation mechanisms further constrain CBM development in China.Finally,continuous exploration of new deep CBM exploration technologies is necessary.Integrating more effective reservoir stimulation technologies is essential to enhance technical adaptability concerning CBM reservoir characteristics,gas occurrence states,and gas generation mechanisms,ultimately achieving efficient CBM development.We conclude that while China possesses a substantial foundation of deep fractured CBM resources,industry development is constrained and requires continuous exploration of new CBM exploration and development technologies to utilize these resources effectively.
基金financially supported by the National Key Research and Development Program of China(2023YFC3503902)the National Natural Science Foundation of China(82430108,82293681(82293680),and 82321004)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(2022B1515120015 and 2024A1515030103)the Guangdong Major Project of Basic and Applied Basic Research(2023B0303000026)the Science and Technology Projects in Guangzhou(202102070001)。
文摘Natural products,with their remarkable structural and biological diversity,have historically served as a vital bridge between chemistry,the life sciences,and medicine.They not only provide essential scaffolds for drug discovery but also inspire innovative strategies in drug development.The biomimetic synthesis of natural products employs principles from biomimicry,applying inspiration from biogenetic processes to design synthetic strategies that mimic biosynthetic processes.Biomimetic synthesis is a highly efficient approach in synthetic chemistry,as it addresses critical challenges in the synthesis of structurally complex natural products with significant biological and medicinal importance.It has gained widespread attention from researchers in chemistry,biology,pharmacy,and related fields,underscoring its interdisciplinary impact.In this perspective,we present recent advances and challenges in the biomimetic synthesis of natural products,along with the significance and prospects of this field,highlighting the transformative potential of biomimetic synthesis strategies for both chemical and biosynthetic approaches to natural product synthesis in the pursuit of novel therapeutic agents.
文摘1.Introduction As China’s first floating production platform in ultra-deepwater,the“Deep Sea No.1”energy station is a milestone in China’s deepwater resource utilization.The energy station is located in the LS17-2 gas field,150 km off the southeast coast of Hainan Island,China.It is a semi-submersible platform(Fig.1)with a displacement of 101 thousand tonnes and an operational draft of 35 to 40 m.The platform is permanently moored in 1422 m water by 16 chain-polyester-chain mooring lines in a 4×4 pattern,and six steel catenary risers(SCRs)are attached to the platform.It is the world’s first and only semi-submersible platform with the function of condensate storage,so it can be regarded as a floating production storage and offloading(FPSO)unit.With the ability to produce 3 billion m3 of natural gas each year(enough for over 10 million families),the Deep Sea No.1 energy station is a key step toward China’s energy independence.The LS17-2 gas field,where the Deep Sea No.1 energy station is located,was discovered in 2014.Plans for its development were made in 2015,followed by research and a preliminary design.Deep Sea No.1 went into operation on June 25,2021,and will operate onsite continuously without dry-docking for 30 years.
基金the Guangdong Provincial Basic and Applied Basic Research Project:Mechanistic Study on the Regulation of Inflammatory Microenvironment and Improvement of Ulcerative Colitis by Lingnan Traditional Medicine Ficus Pandurata Hance through Wilms'Tumor 1-associating Protein-Mediated RNA Methyltransferase Promoting Toll Like Receptor 4 m6A Modification(2023A1515011699)the Zhongshan Medical Research Project:Mechanistic Study on the Action of Xiahuo Pingwei San in the Treatment of Ulcerative Colitis(2022A020446)。
文摘OBJECTIVE:To evaluate the therapeutic effects of Xiahuo Pingwei San(夏藿平胃散,XHPWS)on ulcerative colitis(UC)in mice and to explore the underlying mechanisms through a network pharmacology approach.METHODS:Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS)was utilized to identify the chemical composition and authenticate the active constituents of XHPWS,ensuring rigorous quality control across batches.A dextran sulfate sodium(DSS)-induced UC model was established in C57BL/6 mice,which were treated with XHPWS in vivo.The efficacy against UC was assessed by measuring parameters such as body weight,disease activity index(DAI)scores,and colon length.Levels of inflammatory cytokines,including interleukin-6(IL-6),interleukin-1β(IL-1β),and tumor necrosis factor-alpha(TNF-α),in colonic tissue were evaluated using enzymelinked immunosorbent assay(ELISA).Histological analysis of colon sections was conducted using hematoxylin and eosin staining.A network pharmacology approach was employed to explore the mechanisms of XHPWS and to predict its potential targets in UC treatment.Predicted protein expressions in colonic tissue were validated using immune-ohistochemistry(IHC)and Western blotting techniques.RESULTS:XHPWS effectively alle via ted DSS-induced UC symptoms in mice,as evidenced by restored body weight,reduced colon shortening,and decreased DAI scores.Histopathological examination revealed that XHPWS significantly reduced intestinal inflammatory infiltration,restored intestinal epithelial permeability,and increased goblet cell count.Network pharmacology analysis identified 63 active compounds in XHPWS and suggested that it might target 35 potential proteins associated with UC treatment.Functional enrichment analysis indicated that the protective mechanism of XHPWS could be related to the advanced glycation end products-receptor for advanced glycation end products(AGE-RAGE)signaling pathway.Notably,quercetin,kaempferol,wogonin,and nobiletin,the main components of XHPWS,showed strong correlations with the core targets.Additionally,experimental validation demonstrated that XHPWS significantly decreased levels of inflammatory cytokines interleukin 6(IL-6),interleukin 1 beta(IL-1β),and tumor necrosis factor alpha(TNF-α)in UC mice,while downregulating the expression of proteins related to the AGE-RAGE pathway.CONCLUSION:Our study demonstrated that XHPWS effectively alle via tes colitis symptoms and inflammation in UC mice,potentially through the regulation of the AGE-RAGE pathway.These findings provide strong evidence for the therapeutic potential of XHPWS in UC treatment,thereby broadening its clinical applications.
基金Dean's Office Howard University College of Medicine,Grant/Award Number:Bridge Fund/Pilot Study AwardNational Center on Minority Health and Health Disparities,Grant/Award Number:RCMI/IDC Award U54MD007597National Institute of Child Health and Human Development,Grant/Award Number:R03HD095417 and R16HD116702。
文摘Background:How AMP activated protein kinase(AMPK)signaling regulates mito-chondrial functions and mitophagy in human trophoblast cells remains unclear.This study was designed to investigate potential players mediating the regulation of AMPK on mitochondrial functions and mitophagy by next generation RNA-seq.Methods:We compared ATP production in protein kinase AMP-activated catalytic subunit alpha 1/2(PRKAA1/2)knockdown(AKD)and control BeWo cells using the Seahorse real-time ATP rate test,then analyzed gene expression profiling by RNA-seq.Differentially expressed genes(DEG)were examined by Gene Ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.Then protein-protein interactions(PPI)among mitochondria related genes were fur-ther analyzed using Metascape and Ingenuity Pathway Analysis(IPA)software.Results:Both mitochondrial and glycolytic ATP production in AKD cells were lower than in the control BeWo cells(CT),with a greater reduction of mitochondrial ATP production.A total of 1092 DEGs were identified,with 405 upregulated and 687 downregulated.GO analysis identified 60 genes associated with the term‘mitochon-drion’in the cellular component domain.PPI analysis identified three clusters of mito-chondria related genes,including aldo-keto reductase family 1 member B10 and B15(AKR1B10,AKR1B15),alanyl-tRNA synthetase 1(AARS1),mitochondrial ribosomal protein S6(MRPS6),mitochondrial calcium uniporter dominant negative subunit beta(MCUB)and dihydrolipoamide branched chain transacylase E2(DBT).Conclusions:In summary,this study identified multiple mitochondria related genes regulated by AMPK in BeWo cells,and among them,three clusters of genes may po-tentially contribute to altered mitochondrial functions in response to reduced AMPK signaling.
