A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synth...A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synthetic metabolic engineering offers a method to modify and redesign metabolic pathways to increase the nutritional value of crops.We summarize recent advances in the biofortification of key nutrients including provitamin A,vitamin C,vitamin B9,iron,zinc,anthocyanins,flavonoids,and unsaturated fatty acids.We discuss the potential of multi-gene stacking,gene editing,enzyme engineering,and artificial intelligence in synthetic metabolic engineering.We propose future research directions and potential solutions centered on leveraging AI-driven systems biology,precision gene editing,enzyme engineering,agrobacterium-mediated genotype-independent transformation,and modular metabolic engineering strategies to develop next-generation nutritionally enhanced super crops and transform global food systems.展开更多
Gauss radial basis functions(GRBF)are frequently employed in data fitting and machine learning.Their linear independence property can theoretically guarantee the avoidance of data redundancy.In this paper,one of the m...Gauss radial basis functions(GRBF)are frequently employed in data fitting and machine learning.Their linear independence property can theoretically guarantee the avoidance of data redundancy.In this paper,one of the main contributions is proving this property using linear algebra instead of profound knowledge.This makes it easy to read and understand this fundamental fact.The proof of linear independence of a set of Gauss functions relies on the constructing method for one-dimensional space and on the deducing method for higher dimensions.Additionally,under the condition of preserving the same moments between the original function and interpolating function,both the interpolating existence and uniqueness are proven for GRBF in one-dimensional space.The final work demonstrates the application of the GRBF method to locate lunar olivine.By combining preprocessed data using GRBF with the removing envelope curve method,a program is created to find the position of lunar olivine based on spectrum data,and the numerical experiment shows that it is an effective scheme.展开更多
Saikosaponins are the major pharmacologically active components in Bupleurum genus and exhibit significant application potential in multiple fields such as immune regulation and anti-tumor activity.To elucidate the bi...Saikosaponins are the major pharmacologically active components in Bupleurum genus and exhibit significant application potential in multiple fields such as immune regulation and anti-tumor activity.To elucidate the biosynthetic pathway of saikosaponins,we identified two cytochrome P450 monooxygenases,CYP716A41 and CYP716Y4,in Bupleurum chinense.These enzymes catalyze the C-28 oxidation and C-16 hydroxylation of oleanane-type triterpene skeletons,respectively.The catalytic efficiency of CYP716A41 from a southern B.chinense variety was significantly higher than that from a northern variety.Molecular docking and mutagenesis experiments revealed that amino acid residues at sites 9 and 35 may contribute to this difference in catalytic efficiency.Additionally,under cold stress,the expression levels of both CYP450 genes and the saikosaponin contents in the leaves of southern varieties were significantly higher compared to those in northern varieties.The variation in the catalytic efficiency of CYP716A41 and the differential expression of the two CYP450 genes under cold stress during winter are associated with the differences in saikosaponin biosynthesis in the leaves of southern and northern B.chinense varieties.This is consistent with the distinct medicinal usage practices observed between southern and northern China.展开更多
AIM:To study the relationships between amplitude of low-frequency fluctuations(ALFF)changes and clinical ophthalmic parameters in patients with primary open angle glaucoma(POAG)and analyze the diagnostic value of ALFF...AIM:To study the relationships between amplitude of low-frequency fluctuations(ALFF)changes and clinical ophthalmic parameters in patients with primary open angle glaucoma(POAG)and analyze the diagnostic value of ALFF.METHODS:Twenty-four POAG patients and 24 healthy controls(HCs)underwent resting-state functional magnetic resonance imaging(rs-fMRI).Nonparametric rank-sum tests were used to compare the ALFF values in the slow-4 and slow-5 bands,and Spearman or Pearson correlation analysis was used to assess the correlation between ALFF changes and clinical ophthalmic parameters in POAG patients.Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic performance of the ALFF.RESULTS:There were 16 males in POAG patients(median age 48y)and 12 males in HCs(median age 39y).Compared with HCs,POAG patients presented increased or decreased ALFF values in different brain regions,and similar changes were observed in mild POAG patients.The ALFF values were correlated with retinal nerve fiber layer(RNFL)thickness,inner limiting membrane-retinal pigment epithelium thickness changes and the degree of visual field defects.Analysis of the diagnostic value of the ALFF via ROC curves revealed that the right medial frontal gyrus[area under the curve(AUC)=0.9063]and superior frontal gyrus(AUC=0.9097)had better diagnostic value than did the optic disc area(AUC=0.8019),visual field index(VFI%,AUC=0.8988)and macular parameters.CONCLUSION:POAG patients present altered cortical function that is significantly correlated with the optic nerve and retinal thickness and had good diagnostic value,which may reflect the underlying neuropathological mechanism of POAG.展开更多
Primary human hepatocytes(PHH)are used as the FDA-recognized"gold standard"for liver-related studies in vitro.The world’s first PHH group standard(T/CSCB 0008–2021,CSCB standard)was released by Chinese Soc...Primary human hepatocytes(PHH)are used as the FDA-recognized"gold standard"for liver-related studies in vitro.The world’s first PHH group standard(T/CSCB 0008–2021,CSCB standard)was released by Chinese Society for Cell Biology in 2021.In order to justify this standard,six key quality attributes of ten different batches from commercial PHHs,including cell viability,cell morphology,cell markers,albumin secretion,drug metabolism function and bile secretion,were characterized using the designated test methods in the standard.The PHHs from various batches all exhibited typical hepatocytic morphology,high cell viability,and sufficient albumin secretion;whereas,tremendous variations in cell markers,drug metabolism functions,and bile secretion were unexpectedly detected across the board.Flow cytometric assessment of hepatocyte markers revealed the percentages of ALB^(+)or HNF4A^(+)cells in six batches of PHHs,ranging from 49.4%to 98.9%and from 37.7%to 91.4%,respectively.Single cell transcriptomic analysis also revealed significant cell heterogeneity across the different batches,with the proportions of hepatocytes ranging from 69.2%to 98.9%.Considerable heterogeneity in drug metabolism functions across the batches were also found in substrate clearance rate(SCR)and metabolite formation rate(MFR)for six representative CYP450 enzymes,while the results didn’t influence current SCR attribute of CYP3A4.Metabolic capacity and purity are two independent attributes for PHH.The varied biliary excretion indexes around criteria(30%)indicated heterogeneity of PHH biliary excretion capacity.These results confirmed the robustness of most quality attributes in current CSCB standard,while highlighting the need to refine remaining parameters to enhance its practical applicability.展开更多
Nickel-catalyzed borylation of aryl nonaflates with B2pin2 could be realized,which proceeded effectively by means of C—O bond functionalization to afford a wide variety of valuable arylboronates in moderate to excell...Nickel-catalyzed borylation of aryl nonaflates with B2pin2 could be realized,which proceeded effectively by means of C—O bond functionalization to afford a wide variety of valuable arylboronates in moderate to excellent yields with good functionality compatibility.In addition,the gram-scale synthesis and the application of the approach in the late-stage elaboration of aryl nonaflate derived from pterostilbene could also be achieved.展开更多
Let K_(j)/Q,1≤j≤ν,ν≥2 be quadratic fields with pairwise coprime discriminants Dj,and let τ_(kj)^(K_(j))(n)be the divisor function associated to Dedekind zeta function SK_(j)(s).In this paper,we consider a multid...Let K_(j)/Q,1≤j≤ν,ν≥2 be quadratic fields with pairwise coprime discriminants Dj,and let τ_(kj)^(K_(j))(n)be the divisor function associated to Dedekind zeta function SK_(j)(s).In this paper,we consider a multidimensional general divisor problem related to the τ_(kj)^(K_(j))(n)involving several number fields over square integers,by establishing the corresponding asymptotic formula.As an application,we also obtain the asymptotic formula of variance of these coefi icients.展开更多
Primary hepatic leiomyosarcoma is a very rare disease,accounting for less than 1%of all primary hepatic malignancies[1].As a malignant tumor of the smooth muscle,it originates in the hepatic blood vessels,bile ducts o...Primary hepatic leiomyosarcoma is a very rare disease,accounting for less than 1%of all primary hepatic malignancies[1].As a malignant tumor of the smooth muscle,it originates in the hepatic blood vessels,bile ducts or round ligaments of the liver[2,3].The clinical manifestations are nonspecific,and tumors are usually asymptomatic until they are relatively large in size.Primary hepatic leiomyosarcoma is characterized by a relatively poor prognosis and aggressive metastatic potential[3].The specific etiology and pathogenesis of primary hepatic leiomyosarcoma are still unclear.Several studies indicated that primary hepatic leiomyosarcoma might be related to acquired immune deficiency syndrome[4],Epstein-Barr virus[5],immunosuppression after organ transplantation[6],hepatitis virus[7,8],Hodgkin’s lymphoma[9]and other medical histories.Here,we present a case of primary hepatic leiomyosarcoma.展开更多
This study aims to explore the impact of fatigue induced by different limb exercises on cerebral cortical oxygenation levels and functional connectivity strength using functional near-infrared spectroscopy(fNIRS).Fati...This study aims to explore the impact of fatigue induced by different limb exercises on cerebral cortical oxygenation levels and functional connectivity strength using functional near-infrared spectroscopy(fNIRS).Fatigue was induced using an upper limb ergometer or a lower limb ergometer,with the load increasing gradually each minute.fNIRS covering the prefrontal cortex and motor cortex were used to collect data during the resting state,both before and after fatigue induction.A two-way ANOVA was conducted to examine differences in oxyhemoglobin(HbO_(2))and functional connectivity before and after fatigue induction in both groups,with the significance level set at 0.05.Exercise-induced fatigue in both the upper and lower limbs leads to a significant decrease in cerebral cortical oxygenation levels.Upper limb fatigue leads to a significant reduction in functional connectivity,there were significant decreases in connectivity within the motor cortex,between the motor cortex and frontal regions,and between the right ventrolateral prefrontal cortex and other frontal regions.Conversely,no significant changes were observed before and after lower limb fatigue.Future studies should focus on examining the extent to which how changes in the cerebral cortex,induced by exercise fatigue,are linked to exercise-and/or performance-related outcomes.展开更多
In molybdenum chemistry,the oxidative addition of o-quinone or 1,2-dicarbonyl compounds to molybdenum has been widely used in Mo-catalyzed C—C bond construction.The carbonyl oxidative addition to Mo(0)or Mo(Ⅱ)is the...In molybdenum chemistry,the oxidative addition of o-quinone or 1,2-dicarbonyl compounds to molybdenum has been widely used in Mo-catalyzed C—C bond construction.The carbonyl oxidative addition to Mo(0)or Mo(Ⅱ)is the critical elementary reaction of molybdenum catalysis.However,the relevant density functional theory(DFT)studies are relatively scarce,especially regarding the rational selection of functionals.In this work,14 functionals were employed to investigate the Mo-catalyzed carbonyl oxidative addition step.A benchmark study was carried out to evaluate their performance in structure optimization and energy calculation.Analyses of mean absolute error(MAE)and mean squared error(MSE)indicated that the B3LYP-D3(BJ),TPSSh,and ωB97X-D functionals exhibited superior performance in structure optimization.Using the DLPNO-CCSD(T)functional as the reference,the M06,M06-L,and MN15-L functionals exhibited good performance for energy calculation based on the structures optimized using the B3LYP-D3(BJ)functional.In particular,MN15-L provided the best performance with the smallest MAE and MSE.展开更多
Aspergillus species are ubiquitous fungi that produce mycotoxins(secondary metabolites)known as sterigmatocystin and aflatoxins in many different kinds of foods,which leads to serious contamination in agricultural pro...Aspergillus species are ubiquitous fungi that produce mycotoxins(secondary metabolites)known as sterigmatocystin and aflatoxins in many different kinds of foods,which leads to serious contamination in agricultural products,thereby endangering human health.Extensive studies on Aspergillus fungi have been conducted on growth and development,aflatoxin biosynthesis,and their interactions with environment.Here,we summarized a series of functional genes of the main Aspergillus fungi relative to toxins occurrence in foods,which revealed the signal transduction mechanisms of their involvement in growth and development,toxin production,and response to light,anticipating providing theoretical guidance on developing control and prevention technologies for mycotoxin contamination in agricultural products to ensure food safety.展开更多
Molecular dynamics simulations were carried out to study the effect of chemical short-range order(CSRO)on the primary radiation damage in TiVTaNb high-entropy alloys(HEAs).We have performed displacement cascade simula...Molecular dynamics simulations were carried out to study the effect of chemical short-range order(CSRO)on the primary radiation damage in TiVTaNb high-entropy alloys(HEAs).We have performed displacement cascade simulations to explore the CSRO effect on the generation and evolution behaviors of irradiation defects.The results demonstrate that CSRO can suppress the formation of Frenkel pairs in TiVTaNb HEAs,with the suppression effect becoming more pronounced as the degree of CSRO increases.CSRO can change the types of interstitial defects generated during cascade collisions.Specifically,as the degree of CSRO increases,the proportion of Ti-related interstitials shows a marked enhancement,primarily evidenced by a significant rise in Ti–Ti dumbbells accompanied by a corresponding decrease in Ti–V dumbbells.CSRO exhibits negligible influence on defect clustering and the nucleation and evolution of dislocation loops.Regardless of CSRO conditions,TiVTaNb HEAs preserve exceptional radiation tolerance throughout the cascade damage process,suggesting that the intrinsic properties of this multi-principal element system dominate its radiation response.These findings provide fundamental insights into the CSRO effect on defect formation and evolution behaviors in HEAs,which may provide new design strategies for high-entropy alloys.展开更多
Multivitamins were widely used health supplements that replenished essential nutrients in the human body.Despite their popularity,the impact of multivitamins on the cognitive function of older adults remained unclear ...Multivitamins were widely used health supplements that replenished essential nutrients in the human body.Despite their popularity,the impact of multivitamins on the cognitive function of older adults remained unclear and contentious.This study offered a comprehensive review and meta-analysis of research published until June 2024,analyzing the effects of multivitamins on various cognitive functions in individuals aged 65 and older.We included ten randomized controlled trials encompassing 13,600 participants from multiple databases.These studies evaluated the impact of multivitamins on reasoning,memory,learning,visual perception,idea production,cognitive speed,psychomotor abilities,and higher cognitive functions.Our meta-analysis revealed that multivitamins significantly enhanced delayed free recall (standardized mean difference(SMD)=0.09,95%confidence interval(CI)=[0.05,0.13],P<0.0001).However,they had no substantial effects on immediate free recall(SMD=0.85,95%CI=[-0.18,1.90],P=0.11),idea production(SMD=0.00,95%CI=[-0.04,0.03],P=0.86),or cognitive speed(SMD=0.34,95%CI=[-0.07,0.74],P=0.11).Thus,while multivitamins facilitated delayed free recall,they did not significantly improve other cognitive functions in older adults.展开更多
In this paper,we investigate the uniqueness of meromorphic functions and their derivatives in the unit disc and consider the relations between the Borel points and the shared-values of meromorphic functions in an angu...In this paper,we investigate the uniqueness of meromorphic functions and their derivatives in the unit disc and consider the relations between the Borel points and the shared-values of meromorphic functions in an angular domain by Nevanlinna value distribution theory.An admissible meromorphic function with orde or precise order has Borel point and shares IM common values with its derivative in an angular domain of the unit disc,then the meromorphic function and its derivative are unique.The obtained results improve and generalize some existing results and enrich the uniqueness theory of meromorphic functions.展开更多
Background:Aging is a key risk factor for human health,causing damage to the brain and liver tissues.Accumulating evidence indicates that oxidative stress is a critical driver of the aging process.Shuangshen tablet(SS...Background:Aging is a key risk factor for human health,causing damage to the brain and liver tissues.Accumulating evidence indicates that oxidative stress is a critical driver of the aging process.Shuangshen tablet(SST),a functional food formulated with Ginseng Radix et Rhizoma and Apostichopus japonicus as main ingredients,possesses potential antioxidant and anti-aging properties.Thus,this study aimed to evaluate the anti-aging effects of SST using a D-galactose-induced aging model.Methods:The formula of SST was optimized via single-factor experiments and response surface methodology.Chemical components of SST were identified by UHPLC-Q-Exactive Orbitrap HRMS,and their in vitro antioxidant activity was determined.D-galactose-induced aging mice were intervened with SST,followed by detection of serum oxidative stress and pro-inflammatory factor levels,as well as the activities of superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)content in brain and liver tissues.Hematoxylin and eosin(HE)staining was used to observe brain and liver histopathological changes.Mechanistic studies were conducted to analyze the protein expression levels of Nrf2-HO-1 pathway-related proteins,phosphorylated PI3K(p-PI3K),and phosphorylated AKT(p-AKT).Acute and subacute toxicity tests were performed to evaluate the safety of SST.Results:A total of 46 active components were identified from SST,including ketones,terpenes,phenylpropanoids,and organic acids.SST intervention significantly regulated serum oxidative stress and pro-inflammatory factor levels in aging mice:it reduced MDA content in brain and liver tissues,increased SOD,CAT,and GSH-Px activities,and decreased serum tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)levels.HE staining showed that SST alleviated D-galactose-induced brain and liver damage.Mechanistically,SST mitigated oxidative damage by activating the Nrf2-HO-1 pathway and upregulating the protein expression of p-PI3K and p-AKT.Acute and subacute toxicity tests confirmed the safety of SST.Conclusion:SST can effectively delay the D-galactose-induced aging process by improving the oxidative stress signaling pathway,providing a theoretical basis for the development of antioxidant functional foods.展开更多
Background This study compared knee osteoarthritis(OA)outcomes specific to pain,physical function,and quality of life in later life based on strength training(ST)participation over a lifetime.Methods Participants from...Background This study compared knee osteoarthritis(OA)outcomes specific to pain,physical function,and quality of life in later life based on strength training(ST)participation over a lifetime.Methods Participants from the Osteoarthritis Initiative(n=3192)were grouped by ST engagement during ages 12–18 years,19–34 years,35–49 years,and 50+years.Participants were categorized as:No ST(no ST at any point;61.7±9.0 years(mean±SD)),Some ST(engaged in ST during 1–3 life stages;58.9±8.7 years),and Lifelong ST(consistently engaged in ST across all life stages;55.6±8.1 years).Measures were collected at baseline and Year 4:Western Ontario and McMaster Universities Osteoarthritis Index Scores(WOMAC;pain,daily activities),Knee Injury and Osteoarthritis Outcome Score(KOOS;sports,recreation),Physical Activity Score for the Elderly(PASE),Short Form-12 Physical Component Score(SF-12 PCS),mobility disability,chair rise time,and walking speed(20 m and 400 m).Results At Year 4,the Lifelong ST group reported better WOMAC activity scores in the right knee along with better WOMAC pain,KOOS sports/recreation,and PASE scores compared to other groups(p<0.05).The Lifelong ST group had the lowest incidence of mobility disability of all groups(0.8%vs.2.3%–4.1%;p=0.015)and maintained the fastest walking speeds in Year 4.Conclusion For those with knee OA,ST throughout life may help preserve function and mobility,allowing for greater physical activity engagement while keeping pain levels relatively lower.展开更多
Leaf thickness in rice critically influences photosynthetic efficiency and yield,yet its genetic basis remains poorly understood,with few functional genes previously characterized.In this study,we employ a pangenome-w...Leaf thickness in rice critically influences photosynthetic efficiency and yield,yet its genetic basis remains poorly understood,with few functional genes previously characterized.In this study,we employ a pangenome-wide association study(Pan-GWAS)on 302 diverse rice accessions from southern China,identifying 49 quantitative trait loci(QTLs)associated with leaf thickness.The most significant locus,qLT9,is fine-mapped to a 79-kb region on chromosome 9.Transcriptomic and genomic sequence analyses identify LOC_Os09g33480,which encodes a protein belonging to Multiple Organellar RNA Editing Factor family,as the key candidate gene.Overexpression and complementation transgenic experiments confirm LOC_Os09g33480(OsLT9)as the functional gene underlying qLT9,demonstrating a 24-bp Indel in its promoter correlates with the expression levels and leaf thickness.Notably,OsLT9 overexpression lines show not only thicker leaf,but also significantly enhanced photosynthetic efficiency and grain yield,establishing a link between leaf thickness modulation and yield enhancement.Population genomic analyses indicate strong selection for OsLT9 during domestication and breeding,with modern cultivars favoring thick leaf haplotype of OsLT9.This study establishes OsLT9 as a key regulator controlling leaf thickness in rice,and provides a valuable genetic resource for molecular breeding of high-yielding rice through optimization of plant architecture.展开更多
Submodular optimization is primarily applied in multi-agent systems for tasks such as resource allocation,task assignment,collaborative decision-making,and optimization problems.Maximization of optimizing submodular s...Submodular optimization is primarily applied in multi-agent systems for tasks such as resource allocation,task assignment,collaborative decision-making,and optimization problems.Maximization of optimizing submodular set functions attracts much attention since the 1970s.A large body of work has been done using approximation algorithms.When the dimension of the independent variable of the set function changes from one tok,it is called ak-submodular set function.Thek-submodular set function,a generalization of the classical submodular set function,arises in diverse fields with varied applications.In many practical scenarios,quantifying the degree of closeness to submodularity becomes essential,leading to concepts such as approximately submodular set functions and the diminishing-return(DR) ratio.This paper investigates ak-dimensional set function under matroid constraints,which may lack full submodularity.Instead,we focus on an approximately non-ksubmodular set function characterized by its DR ratio.Employing a greedy algorithmic approach,we derive an approximation guarantee for this problem.Notably,when the DR ratio is set to one,our results align with existing findings in the literature.Experimental results demonstrate the superiority of our algorithm over the baselines.展开更多
[Objectives]To investigate the efficacy and potential mechanism of the topical preparation Jineijin-Shanzha Patch(composed of Galli Gigerii Endothelium Corneum and Crataegi Fructus)in improving functional dyspepsia(FD...[Objectives]To investigate the efficacy and potential mechanism of the topical preparation Jineijin-Shanzha Patch(composed of Galli Gigerii Endothelium Corneum and Crataegi Fructus)in improving functional dyspepsia(FD)based on network pharmacology.[Methods]Firstly,we reviewed the existing research progress on each constituent drug of the Jineijin Shanzha Patch for FD improvement.Following this,identified overlapping genes were utilized to construct both a"Drug-Active Component-FD Target"network and a Protein-Protein Interaction(PPI)network specific to the patch.In addition,Gene Ontology(GO)analysis was carried out.[Results]We identified that the 13 herbs in the Jineijin Shanzha Patch are mainly used for food stagnation,qi stagnation,and spleen deficiency.Screening revealed 43 active patch components,1414 FD-related targets,and 284 shared targets between them.The PPI network analysis further identified the top 10 core targets from these shared targets.From the"Drug-Active Component-FD Target"network,we identified the core elements.These included the herbal components Vignae Semen(from Liushenqu),Crataegi Fructus,and Pseudostellariae Radix;the active components quercetin,genistein,and apigenin;and the key targets CASP3,BCL2,and CASP9.GO analysis of the 284 overlapping targets indicated that the Jineijin Shanzha Patch may exert its therapeutic effects via regulation of biological processes such as the response to lipopolysaccharide,response to bacterium-derived molecules,and regulation of the apoptotic signaling pathway.[Conclusions]The main active components of the Jineijin Shanzha Patch(quercetin,genistein,and apigenin)may improve FD by modulating signaling pathways such as the response to lipopolysaccharide,response to bacterium-derived molecules,and regulation of the apoptotic signaling pathway,thereby acting on key targets including CASP3,BCL2,and CASP9.展开更多
Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minima...Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.展开更多
基金supported by grants from the Guangxi Science and Technology Major Project(GKAA24206023)the Biological Breeding-National Science and Technology Major Project(2024ZD04077)+2 种基金the National Natural Science Foundation of China(32272120)the National Key Research and Development Program of China(2024YFF1000800)the Guangdong Basic Research Center of Excellence for Precise Breeding of Future Crops Major Project(FCBRCE-202502,FCBRCE-202504).
文摘A growing global population and the increasing prevalence of diet-related health issues such as“hidden hunger”,obesity,hypertension,and diabetes necessitate a fundamental rethinking of crop design and breeding.Synthetic metabolic engineering offers a method to modify and redesign metabolic pathways to increase the nutritional value of crops.We summarize recent advances in the biofortification of key nutrients including provitamin A,vitamin C,vitamin B9,iron,zinc,anthocyanins,flavonoids,and unsaturated fatty acids.We discuss the potential of multi-gene stacking,gene editing,enzyme engineering,and artificial intelligence in synthetic metabolic engineering.We propose future research directions and potential solutions centered on leveraging AI-driven systems biology,precision gene editing,enzyme engineering,agrobacterium-mediated genotype-independent transformation,and modular metabolic engineering strategies to develop next-generation nutritionally enhanced super crops and transform global food systems.
基金Supported by the National Basic Research Program of China(2012CB025904)Zhengzhou Shengda University of Economics,Business and Management(SD-YB2025085)。
文摘Gauss radial basis functions(GRBF)are frequently employed in data fitting and machine learning.Their linear independence property can theoretically guarantee the avoidance of data redundancy.In this paper,one of the main contributions is proving this property using linear algebra instead of profound knowledge.This makes it easy to read and understand this fundamental fact.The proof of linear independence of a set of Gauss functions relies on the constructing method for one-dimensional space and on the deducing method for higher dimensions.Additionally,under the condition of preserving the same moments between the original function and interpolating function,both the interpolating existence and uniqueness are proven for GRBF in one-dimensional space.The final work demonstrates the application of the GRBF method to locate lunar olivine.By combining preprocessed data using GRBF with the removing envelope curve method,a program is created to find the position of lunar olivine based on spectrum data,and the numerical experiment shows that it is an effective scheme.
基金supported by CARS(CARS-21),the CAMS Innovation Fund for Medical Sciences(2021-I2M-1-032)the Science and Technology Department of Xizang(XZ202401ZY0020)+2 种基金the Science and Technology Department of Sichuan Province(2023YFH0044,2023YFH0018)the Sichuan Province Science Foundation for Distinguished Young Scholars(2022JDJQ0006)the Doctoral Fund of Southwest University of Science and Technology(19ZX7117,21ZX7116).
文摘Saikosaponins are the major pharmacologically active components in Bupleurum genus and exhibit significant application potential in multiple fields such as immune regulation and anti-tumor activity.To elucidate the biosynthetic pathway of saikosaponins,we identified two cytochrome P450 monooxygenases,CYP716A41 and CYP716Y4,in Bupleurum chinense.These enzymes catalyze the C-28 oxidation and C-16 hydroxylation of oleanane-type triterpene skeletons,respectively.The catalytic efficiency of CYP716A41 from a southern B.chinense variety was significantly higher than that from a northern variety.Molecular docking and mutagenesis experiments revealed that amino acid residues at sites 9 and 35 may contribute to this difference in catalytic efficiency.Additionally,under cold stress,the expression levels of both CYP450 genes and the saikosaponin contents in the leaves of southern varieties were significantly higher compared to those in northern varieties.The variation in the catalytic efficiency of CYP716A41 and the differential expression of the two CYP450 genes under cold stress during winter are associated with the differences in saikosaponin biosynthesis in the leaves of southern and northern B.chinense varieties.This is consistent with the distinct medicinal usage practices observed between southern and northern China.
基金Supported by National Natural Science Foundation of China(No.82260203).
文摘AIM:To study the relationships between amplitude of low-frequency fluctuations(ALFF)changes and clinical ophthalmic parameters in patients with primary open angle glaucoma(POAG)and analyze the diagnostic value of ALFF.METHODS:Twenty-four POAG patients and 24 healthy controls(HCs)underwent resting-state functional magnetic resonance imaging(rs-fMRI).Nonparametric rank-sum tests were used to compare the ALFF values in the slow-4 and slow-5 bands,and Spearman or Pearson correlation analysis was used to assess the correlation between ALFF changes and clinical ophthalmic parameters in POAG patients.Receiver operating characteristic(ROC)curves were used to evaluate the diagnostic performance of the ALFF.RESULTS:There were 16 males in POAG patients(median age 48y)and 12 males in HCs(median age 39y).Compared with HCs,POAG patients presented increased or decreased ALFF values in different brain regions,and similar changes were observed in mild POAG patients.The ALFF values were correlated with retinal nerve fiber layer(RNFL)thickness,inner limiting membrane-retinal pigment epithelium thickness changes and the degree of visual field defects.Analysis of the diagnostic value of the ALFF via ROC curves revealed that the right medial frontal gyrus[area under the curve(AUC)=0.9063]and superior frontal gyrus(AUC=0.9097)had better diagnostic value than did the optic disc area(AUC=0.8019),visual field index(VFI%,AUC=0.8988)and macular parameters.CONCLUSION:POAG patients present altered cortical function that is significantly correlated with the optic nerve and retinal thickness and had good diagnostic value,which may reflect the underlying neuropathological mechanism of POAG.
基金supported by the Strategic Priority Research Program of Chinese Academy of Sciences(XDB1150102)National Science Foundation of China(82173878 and 82172001)Shanghai Municipal Science and Technology Major Project.
文摘Primary human hepatocytes(PHH)are used as the FDA-recognized"gold standard"for liver-related studies in vitro.The world’s first PHH group standard(T/CSCB 0008–2021,CSCB standard)was released by Chinese Society for Cell Biology in 2021.In order to justify this standard,six key quality attributes of ten different batches from commercial PHHs,including cell viability,cell morphology,cell markers,albumin secretion,drug metabolism function and bile secretion,were characterized using the designated test methods in the standard.The PHHs from various batches all exhibited typical hepatocytic morphology,high cell viability,and sufficient albumin secretion;whereas,tremendous variations in cell markers,drug metabolism functions,and bile secretion were unexpectedly detected across the board.Flow cytometric assessment of hepatocyte markers revealed the percentages of ALB^(+)or HNF4A^(+)cells in six batches of PHHs,ranging from 49.4%to 98.9%and from 37.7%to 91.4%,respectively.Single cell transcriptomic analysis also revealed significant cell heterogeneity across the different batches,with the proportions of hepatocytes ranging from 69.2%to 98.9%.Considerable heterogeneity in drug metabolism functions across the batches were also found in substrate clearance rate(SCR)and metabolite formation rate(MFR)for six representative CYP450 enzymes,while the results didn’t influence current SCR attribute of CYP3A4.Metabolic capacity and purity are two independent attributes for PHH.The varied biliary excretion indexes around criteria(30%)indicated heterogeneity of PHH biliary excretion capacity.These results confirmed the robustness of most quality attributes in current CSCB standard,while highlighting the need to refine remaining parameters to enhance its practical applicability.
文摘Nickel-catalyzed borylation of aryl nonaflates with B2pin2 could be realized,which proceeded effectively by means of C—O bond functionalization to afford a wide variety of valuable arylboronates in moderate to excellent yields with good functionality compatibility.In addition,the gram-scale synthesis and the application of the approach in the late-stage elaboration of aryl nonaflate derived from pterostilbene could also be achieved.
基金Supported in part by NSFC(Nos.12401011,12201214)National Key Research and Development Program of China(No.2021YFA1000700)+3 种基金Shaanxi Fundamental Science Research Project for Mathematics and Physics(No.23JSQ053)Science and Technology Program for Youth New Star of Shaanxi Province(No.2025ZC-KJXX-29)Natural Science Basic Research Program of Shaanxi Province(No.2025JC-YBQN-091)Scientific Research Foundation for Young Talents of WNU(No.2024XJ-QNRC-01)。
文摘Let K_(j)/Q,1≤j≤ν,ν≥2 be quadratic fields with pairwise coprime discriminants Dj,and let τ_(kj)^(K_(j))(n)be the divisor function associated to Dedekind zeta function SK_(j)(s).In this paper,we consider a multidimensional general divisor problem related to the τ_(kj)^(K_(j))(n)involving several number fields over square integers,by establishing the corresponding asymptotic formula.As an application,we also obtain the asymptotic formula of variance of these coefi icients.
文摘Primary hepatic leiomyosarcoma is a very rare disease,accounting for less than 1%of all primary hepatic malignancies[1].As a malignant tumor of the smooth muscle,it originates in the hepatic blood vessels,bile ducts or round ligaments of the liver[2,3].The clinical manifestations are nonspecific,and tumors are usually asymptomatic until they are relatively large in size.Primary hepatic leiomyosarcoma is characterized by a relatively poor prognosis and aggressive metastatic potential[3].The specific etiology and pathogenesis of primary hepatic leiomyosarcoma are still unclear.Several studies indicated that primary hepatic leiomyosarcoma might be related to acquired immune deficiency syndrome[4],Epstein-Barr virus[5],immunosuppression after organ transplantation[6],hepatitis virus[7,8],Hodgkin’s lymphoma[9]and other medical histories.Here,we present a case of primary hepatic leiomyosarcoma.
基金supported by National Natural Science Foundation of China[NO.11932013].
文摘This study aims to explore the impact of fatigue induced by different limb exercises on cerebral cortical oxygenation levels and functional connectivity strength using functional near-infrared spectroscopy(fNIRS).Fatigue was induced using an upper limb ergometer or a lower limb ergometer,with the load increasing gradually each minute.fNIRS covering the prefrontal cortex and motor cortex were used to collect data during the resting state,both before and after fatigue induction.A two-way ANOVA was conducted to examine differences in oxyhemoglobin(HbO_(2))and functional connectivity before and after fatigue induction in both groups,with the significance level set at 0.05.Exercise-induced fatigue in both the upper and lower limbs leads to a significant decrease in cerebral cortical oxygenation levels.Upper limb fatigue leads to a significant reduction in functional connectivity,there were significant decreases in connectivity within the motor cortex,between the motor cortex and frontal regions,and between the right ventrolateral prefrontal cortex and other frontal regions.Conversely,no significant changes were observed before and after lower limb fatigue.Future studies should focus on examining the extent to which how changes in the cerebral cortex,induced by exercise fatigue,are linked to exercise-and/or performance-related outcomes.
基金Project supported by the Fundamental Research Funds for the Central Universities(No.2042025kf0052)。
文摘In molybdenum chemistry,the oxidative addition of o-quinone or 1,2-dicarbonyl compounds to molybdenum has been widely used in Mo-catalyzed C—C bond construction.The carbonyl oxidative addition to Mo(0)or Mo(Ⅱ)is the critical elementary reaction of molybdenum catalysis.However,the relevant density functional theory(DFT)studies are relatively scarce,especially regarding the rational selection of functionals.In this work,14 functionals were employed to investigate the Mo-catalyzed carbonyl oxidative addition step.A benchmark study was carried out to evaluate their performance in structure optimization and energy calculation.Analyses of mean absolute error(MAE)and mean squared error(MSE)indicated that the B3LYP-D3(BJ),TPSSh,and ωB97X-D functionals exhibited superior performance in structure optimization.Using the DLPNO-CCSD(T)functional as the reference,the M06,M06-L,and MN15-L functionals exhibited good performance for energy calculation based on the structures optimized using the B3LYP-D3(BJ)functional.In particular,MN15-L provided the best performance with the smallest MAE and MSE.
基金supported by the key project of National Natural Sciences Foundation of China(U22A20551,32030085)the Major Project of Hubei Hongshan Laboratory,China(2021hszd015)+2 种基金the Hubei Province Major Science and Technology Special Project,China(2023BBA002)the National Natural Sciences Foundation of China(U22A20551)the National Natural Science Foundation of China Excellent Youth Fund(32422072)。
文摘Aspergillus species are ubiquitous fungi that produce mycotoxins(secondary metabolites)known as sterigmatocystin and aflatoxins in many different kinds of foods,which leads to serious contamination in agricultural products,thereby endangering human health.Extensive studies on Aspergillus fungi have been conducted on growth and development,aflatoxin biosynthesis,and their interactions with environment.Here,we summarized a series of functional genes of the main Aspergillus fungi relative to toxins occurrence in foods,which revealed the signal transduction mechanisms of their involvement in growth and development,toxin production,and response to light,anticipating providing theoretical guidance on developing control and prevention technologies for mycotoxin contamination in agricultural products to ensure food safety.
基金Project supported by the Youth Program of the National Natural Science Foundation of China(Grant No.12405324)the CNNC Science Fund for Talented Young Scholars(Grant No.24940)the CNNC Basic Science Fund(Grant No.24851)。
文摘Molecular dynamics simulations were carried out to study the effect of chemical short-range order(CSRO)on the primary radiation damage in TiVTaNb high-entropy alloys(HEAs).We have performed displacement cascade simulations to explore the CSRO effect on the generation and evolution behaviors of irradiation defects.The results demonstrate that CSRO can suppress the formation of Frenkel pairs in TiVTaNb HEAs,with the suppression effect becoming more pronounced as the degree of CSRO increases.CSRO can change the types of interstitial defects generated during cascade collisions.Specifically,as the degree of CSRO increases,the proportion of Ti-related interstitials shows a marked enhancement,primarily evidenced by a significant rise in Ti–Ti dumbbells accompanied by a corresponding decrease in Ti–V dumbbells.CSRO exhibits negligible influence on defect clustering and the nucleation and evolution of dislocation loops.Regardless of CSRO conditions,TiVTaNb HEAs preserve exceptional radiation tolerance throughout the cascade damage process,suggesting that the intrinsic properties of this multi-principal element system dominate its radiation response.These findings provide fundamental insights into the CSRO effect on defect formation and evolution behaviors in HEAs,which may provide new design strategies for high-entropy alloys.
基金supported by the Fundamental Research Funds for the Central Universities(2042023gf0003)Hubei Provincial Natural Science Foundation of China(2024AFD126)National Key Research and Development Program of China(2023YFF1104404).
文摘Multivitamins were widely used health supplements that replenished essential nutrients in the human body.Despite their popularity,the impact of multivitamins on the cognitive function of older adults remained unclear and contentious.This study offered a comprehensive review and meta-analysis of research published until June 2024,analyzing the effects of multivitamins on various cognitive functions in individuals aged 65 and older.We included ten randomized controlled trials encompassing 13,600 participants from multiple databases.These studies evaluated the impact of multivitamins on reasoning,memory,learning,visual perception,idea production,cognitive speed,psychomotor abilities,and higher cognitive functions.Our meta-analysis revealed that multivitamins significantly enhanced delayed free recall (standardized mean difference(SMD)=0.09,95%confidence interval(CI)=[0.05,0.13],P<0.0001).However,they had no substantial effects on immediate free recall(SMD=0.85,95%CI=[-0.18,1.90],P=0.11),idea production(SMD=0.00,95%CI=[-0.04,0.03],P=0.86),or cognitive speed(SMD=0.34,95%CI=[-0.07,0.74],P=0.11).Thus,while multivitamins facilitated delayed free recall,they did not significantly improve other cognitive functions in older adults.
文摘In this paper,we investigate the uniqueness of meromorphic functions and their derivatives in the unit disc and consider the relations between the Borel points and the shared-values of meromorphic functions in an angular domain by Nevanlinna value distribution theory.An admissible meromorphic function with orde or precise order has Borel point and shares IM common values with its derivative in an angular domain of the unit disc,then the meromorphic function and its derivative are unique.The obtained results improve and generalize some existing results and enrich the uniqueness theory of meromorphic functions.
基金funded by Jilin Provincial Science and Technology Development Plan Project-Research and Development of Shuangshen Tablets(20210401123YY)Jilin Provincial Science and Technology Development Plan Project-Jilin Province High-quality and Authentic Medicinal Materials(Ginseng)Science and Technology Demonstration Base+(Ji'an Dadi Ginseng Industry Co.,Ltd.Ginseng Planting Base)(20220401114YY)Scientific Research Fund of Hebei Normal University of Science&Technology(2024YB019).
文摘Background:Aging is a key risk factor for human health,causing damage to the brain and liver tissues.Accumulating evidence indicates that oxidative stress is a critical driver of the aging process.Shuangshen tablet(SST),a functional food formulated with Ginseng Radix et Rhizoma and Apostichopus japonicus as main ingredients,possesses potential antioxidant and anti-aging properties.Thus,this study aimed to evaluate the anti-aging effects of SST using a D-galactose-induced aging model.Methods:The formula of SST was optimized via single-factor experiments and response surface methodology.Chemical components of SST were identified by UHPLC-Q-Exactive Orbitrap HRMS,and their in vitro antioxidant activity was determined.D-galactose-induced aging mice were intervened with SST,followed by detection of serum oxidative stress and pro-inflammatory factor levels,as well as the activities of superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)content in brain and liver tissues.Hematoxylin and eosin(HE)staining was used to observe brain and liver histopathological changes.Mechanistic studies were conducted to analyze the protein expression levels of Nrf2-HO-1 pathway-related proteins,phosphorylated PI3K(p-PI3K),and phosphorylated AKT(p-AKT).Acute and subacute toxicity tests were performed to evaluate the safety of SST.Results:A total of 46 active components were identified from SST,including ketones,terpenes,phenylpropanoids,and organic acids.SST intervention significantly regulated serum oxidative stress and pro-inflammatory factor levels in aging mice:it reduced MDA content in brain and liver tissues,increased SOD,CAT,and GSH-Px activities,and decreased serum tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)levels.HE staining showed that SST alleviated D-galactose-induced brain and liver damage.Mechanistically,SST mitigated oxidative damage by activating the Nrf2-HO-1 pathway and upregulating the protein expression of p-PI3K and p-AKT.Acute and subacute toxicity tests confirmed the safety of SST.Conclusion:SST can effectively delay the D-galactose-induced aging process by improving the oxidative stress signaling pathway,providing a theoretical basis for the development of antioxidant functional foods.
文摘Background This study compared knee osteoarthritis(OA)outcomes specific to pain,physical function,and quality of life in later life based on strength training(ST)participation over a lifetime.Methods Participants from the Osteoarthritis Initiative(n=3192)were grouped by ST engagement during ages 12–18 years,19–34 years,35–49 years,and 50+years.Participants were categorized as:No ST(no ST at any point;61.7±9.0 years(mean±SD)),Some ST(engaged in ST during 1–3 life stages;58.9±8.7 years),and Lifelong ST(consistently engaged in ST across all life stages;55.6±8.1 years).Measures were collected at baseline and Year 4:Western Ontario and McMaster Universities Osteoarthritis Index Scores(WOMAC;pain,daily activities),Knee Injury and Osteoarthritis Outcome Score(KOOS;sports,recreation),Physical Activity Score for the Elderly(PASE),Short Form-12 Physical Component Score(SF-12 PCS),mobility disability,chair rise time,and walking speed(20 m and 400 m).Results At Year 4,the Lifelong ST group reported better WOMAC activity scores in the right knee along with better WOMAC pain,KOOS sports/recreation,and PASE scores compared to other groups(p<0.05).The Lifelong ST group had the lowest incidence of mobility disability of all groups(0.8%vs.2.3%–4.1%;p=0.015)and maintained the fastest walking speeds in Year 4.Conclusion For those with knee OA,ST throughout life may help preserve function and mobility,allowing for greater physical activity engagement while keeping pain levels relatively lower.
基金supported by the National Natural Science Foundation of China(32301845)GuangDong Basic and Applied Basic Research Foundation(2022A1515012339)+3 种基金the National Key R&D Program of China(2024YFD1200801)Seed industry revitalization project of special fund for rural revitalization strategy in Guangdong Province(2024-NPY-00-001)Modern Seed Industry Innovation Capacity Enhancement Progject of Guangdong Academy of Agricultural Sciences,Elite Rice Plan of GDRRI(2023YG01)Guangdong Key Laboratory of Rice Science and Technology(2023B1212060042).
文摘Leaf thickness in rice critically influences photosynthetic efficiency and yield,yet its genetic basis remains poorly understood,with few functional genes previously characterized.In this study,we employ a pangenome-wide association study(Pan-GWAS)on 302 diverse rice accessions from southern China,identifying 49 quantitative trait loci(QTLs)associated with leaf thickness.The most significant locus,qLT9,is fine-mapped to a 79-kb region on chromosome 9.Transcriptomic and genomic sequence analyses identify LOC_Os09g33480,which encodes a protein belonging to Multiple Organellar RNA Editing Factor family,as the key candidate gene.Overexpression and complementation transgenic experiments confirm LOC_Os09g33480(OsLT9)as the functional gene underlying qLT9,demonstrating a 24-bp Indel in its promoter correlates with the expression levels and leaf thickness.Notably,OsLT9 overexpression lines show not only thicker leaf,but also significantly enhanced photosynthetic efficiency and grain yield,establishing a link between leaf thickness modulation and yield enhancement.Population genomic analyses indicate strong selection for OsLT9 during domestication and breeding,with modern cultivars favoring thick leaf haplotype of OsLT9.This study establishes OsLT9 as a key regulator controlling leaf thickness in rice,and provides a valuable genetic resource for molecular breeding of high-yielding rice through optimization of plant architecture.
基金Supported by the Natural Science Foundation of Shandong Province (No.ZR2023MA031)the Natural Science Foundation of China (No.12201619)。
文摘Submodular optimization is primarily applied in multi-agent systems for tasks such as resource allocation,task assignment,collaborative decision-making,and optimization problems.Maximization of optimizing submodular set functions attracts much attention since the 1970s.A large body of work has been done using approximation algorithms.When the dimension of the independent variable of the set function changes from one tok,it is called ak-submodular set function.Thek-submodular set function,a generalization of the classical submodular set function,arises in diverse fields with varied applications.In many practical scenarios,quantifying the degree of closeness to submodularity becomes essential,leading to concepts such as approximately submodular set functions and the diminishing-return(DR) ratio.This paper investigates ak-dimensional set function under matroid constraints,which may lack full submodularity.Instead,we focus on an approximately non-ksubmodular set function characterized by its DR ratio.Employing a greedy algorithmic approach,we derive an approximation guarantee for this problem.Notably,when the DR ratio is set to one,our results align with existing findings in the literature.Experimental results demonstrate the superiority of our algorithm over the baselines.
基金Supported by Putuo District Science and Technology R&D Platform Project,Shanghai(2024QX04).
文摘[Objectives]To investigate the efficacy and potential mechanism of the topical preparation Jineijin-Shanzha Patch(composed of Galli Gigerii Endothelium Corneum and Crataegi Fructus)in improving functional dyspepsia(FD)based on network pharmacology.[Methods]Firstly,we reviewed the existing research progress on each constituent drug of the Jineijin Shanzha Patch for FD improvement.Following this,identified overlapping genes were utilized to construct both a"Drug-Active Component-FD Target"network and a Protein-Protein Interaction(PPI)network specific to the patch.In addition,Gene Ontology(GO)analysis was carried out.[Results]We identified that the 13 herbs in the Jineijin Shanzha Patch are mainly used for food stagnation,qi stagnation,and spleen deficiency.Screening revealed 43 active patch components,1414 FD-related targets,and 284 shared targets between them.The PPI network analysis further identified the top 10 core targets from these shared targets.From the"Drug-Active Component-FD Target"network,we identified the core elements.These included the herbal components Vignae Semen(from Liushenqu),Crataegi Fructus,and Pseudostellariae Radix;the active components quercetin,genistein,and apigenin;and the key targets CASP3,BCL2,and CASP9.GO analysis of the 284 overlapping targets indicated that the Jineijin Shanzha Patch may exert its therapeutic effects via regulation of biological processes such as the response to lipopolysaccharide,response to bacterium-derived molecules,and regulation of the apoptotic signaling pathway.[Conclusions]The main active components of the Jineijin Shanzha Patch(quercetin,genistein,and apigenin)may improve FD by modulating signaling pathways such as the response to lipopolysaccharide,response to bacterium-derived molecules,and regulation of the apoptotic signaling pathway,thereby acting on key targets including CASP3,BCL2,and CASP9.
基金National Natural Science Foundation of China,Grant/Award Number:82172140。
文摘Background:Targeted delivery of biological macromolecules to the small intestine remains challenging due to their susceptibility to degradation in the hostile gastric environment.Methods:This study introduces a minimally invasive,in situ injection technique for the murine small intestine that facilitates localized luminal delivery while circumventing gastric barriers.The procedure involves a small abdominal incision for direct injection into the duodenum near the pylorus.Postsurgical monitoring of physiological parameters,systemic inflammatory markers,liver function,and intestinal integrity was conducted over 72 h.Histopathological analysis was performed.The delivery of the functional protein TAT-EGFP(Tat protein fused to enhanced green fluorescent protein)to intestinal epithelial cells was evaluated and compared with oral gavage.As a proof of concept,single-cell RNA sequencing of the intestinal epithelium was performed after high-mobility group box 1 administration.Results:Postsurgical monitoring indicated only transient,anesthesia-related hypo-thermia and minor behavioral alterations.No significant changes were observed over 72 h in body weight,core temperature,clinical severity scores,systemic inflammatory markers(C-reactive protein and leukocytes),liver function(alanine aminotransferase),or intestinal integrity.Histopathological analysis confirmed preserved tissue architec-ture and normal digestive,absorptive,and barrier functions.The model successfully delivered TAT-EGFP to intestinal epithelial cells,an outcome not achievable via oral gavage due to gastric degradation.Single-cell RNA sequencing of the intestinal epi-thelium after high-mobility group box 1 administration revealed inflammatory gene expression patterns in specific epithelial subpopulations.Conclusions:Compared to traditional methods such as oral gavage or organoid cul-ture,this technique offers precise,degradation-resistant delivery of macromolecules in a physiological context.The model's versatility makes it a powerful platform for intestinal research,with applications in drug delivery assessment,gene therapy evalu-ation,and host-microbiota interaction studies.
