Background:Colorectal cancer(CRC)has become one of the major life-threatening complications in patients with inflammatory bowel disease(IBD),which includes ulcerative colitis(UC)and Crohn's disease(CD).This study ...Background:Colorectal cancer(CRC)has become one of the major life-threatening complications in patients with inflammatory bowel disease(IBD),which includes ulcerative colitis(UC)and Crohn's disease(CD).This study aimed to explore the clinicalpathologic similarities and differences in the IBD-associ吐ed CRC(IBD-CRC)between patients in China and Canada.Methods:Data of 78 patients with IBD-CRC retrospectively retrieved from two representative medical institutions in Beijing(China)and Calgary(Canada)over the same past 13 years,including 25(22 UC-associated and three CD-associated)from Beijing group and 53(32 UC-associated and 21 CD-associated)from Calgary group,were compared with regards to their clinical and pathologic characteristics.Results:Several known features of IBD-CRC were seen in both groups,including long duration and large extent of colitis,active inflammation background,multifocal lesions,and advanced tumor-node-metastasis stage.Beijing group showed a significantly higher percentage of UC(88.0%vs.60.4%,P=0.018),younger age at diagnosis of CRC(48.6±12.8 years vs.61.6±14.7 years,P<0.001),lower ratio of mucinous adenocarcinoma(7.1%us.42.4%,P=0.001)compared with Calgary group.None of the Beijing group had concurrent primary sclerosing cholangitis,while 5.7%of Calgary group did.Surveillance colonoscopy favored the detection rate of precancerous lesions(41.4%vs.17.0%,P=0.002).Conclusions:As compared with patients from the Calgary group,the IBD-CRC patients in Beijing group were younger,less CDassociated and had less mucinous features,otherwise they were similar in many common features.展开更多
Zn-air battery(ZAB)has garnered significant attention owing to its environmental friendliness and safety attributes.A critical challenge in advancing ZAB technology lies in the development of high-performance and cost...Zn-air battery(ZAB)has garnered significant attention owing to its environmental friendliness and safety attributes.A critical challenge in advancing ZAB technology lies in the development of high-performance and cost-effective electrocatalysts for oxygen redox reactions(OER and ORR).Herein,we report Co/Fe carbon-supported composites as efficient bifunctional catalyst encapsulated in oxidative ammonolysis modified lignin-derived N-doped biochar(Co Fe-Co_(x)N@NOALC).It exhibited exceptional electrochemical performance in aqueous ZAB owing to their uniform dispersed and small particle size,with a peak power density of 154 mW/cm^(2)and a specific capacity of 770 mAh/g.Most notably,it exhibited a long cycle stability,surpassing 1500 h at a current density of 10 mA/cm^(2),with a mere 11.4%decrease in the chargedischarge efficiency of the battery.This study proposes a viable strategy for enhancing the performance and reducing the cost of Zn-air batteries through the utilization of biomass-derived materials.展开更多
Rheumatoid arthritis(RA)is a refractory autoimmune disease with limited treatment options.Plantderived exosomes-like nanovesicles(PDENs)have emerged as a novel nanomedical approach,with the inherent bioactive compound...Rheumatoid arthritis(RA)is a refractory autoimmune disease with limited treatment options.Plantderived exosomes-like nanovesicles(PDENs)have emerged as a novel nanomedical approach,with the inherent bioactive compounds from their source plants.The roots of Morinda officinalis How.(MO),a Chinese herb,exhibit notable anti-inflammatory activities and hold promising therapeutic value.We engineered a joint-targe ting delivery system(termed MOE@EM)by masking MO-derived exosomes-like nanovesicles(MOE)with erythrocyte membrane(EM).This biomimetic strategy,using EM camouflage,is intended to improve the in vivo fate of MOE.We investigated the antioxidative and anti-inflammatory activities,immunogenicity,drug accumulation in the joint,and therapeutic efficacy to ascertain its suitability for RA therapy.UV irradiation significantly increased the activities of catalase and peroxidase of MOE,and enhanced the anti-inflammatory effects via the Wnt/β-catenin pathway.Furthermore,MOE@EM markedly attenuated dendritic cell activation.MOE@EM exhibited joint-specific delivery,with substantial reduction in paw swelling,and favorable modulation of immune microenvironment.展开更多
BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)cortic...BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.展开更多
This study presents new methods to effectively model the anisotropic yielding and hardening behavior of laser powder bed fusion fabricated aluminum alloy under both monotonic and cyclic loading conditions.The proposed...This study presents new methods to effectively model the anisotropic yielding and hardening behavior of laser powder bed fusion fabricated aluminum alloy under both monotonic and cyclic loading conditions.The proposed model combines the yield surface-interpolation method to accurately describe the anisotropic hardening rates in various directions,with the Chaboche kinematic hardening rule to precisely reflect the cyclic characteristics.For numerical implementation of the combined anisotropic and cyclic constitutive model,a fully implicit stress integration algorithm based on return mapping method is provided.Moreover,the multiple parameters associated with the model are categorized and identified in an uncoupled manner.The isotropic and cyclic hardening parameters are determined by an inverse method,and the stability of the optimization outcomes is validated by applying different starting points for the parameters.Particularly,the back-stress effect on the identification of anisotropic parameters associated with the stress invariant-based Hill48 yield function is considered for the first time.This consideration leads to an improved prediction accuracy compared to the identification of anisotropic parameters without considering back-stress effect.The combined anisotropic and cyclic constitutive model,along with the calibrated parameters,are proven capable of accurately reproducing the intricate deformation behavior of laser powder bed fusion fabricated AlSi10Mg.展开更多
Meiosis,a critical process for sexual reproduction,requires precise regulation to ensure the correct progression of meiotic stages.In yeast and animals,errors in meiotic recombination and homologous chromosomes synaps...Meiosis,a critical process for sexual reproduction,requires precise regulation to ensure the correct progression of meiotic stages.In yeast and animals,errors in meiotic recombination and homologous chromosomes synapsis bring a surveillance mechanism named pachytene checkpoint to prevent pachytene exit.However,most plant mutants with defects in meiotic prophase I continue cell cycle progression,which hindered the characterization of factors controlling the prophase I to metaphase I transition.Here,we characterized a male-sterile mutant in maize,prolonged prophase1(pp1),which exhibited pachytene and diakinesis arrest in male meiosis,and abnormal chromatin condensation.Using mapbased cloning,the PP1 gene was isolated as a PHD family transcription factor,and its transcripts of PP1 were preferentially accumulated in tapetum and male germline cells during microsporogenesis.Transcriptomic analysis of the pp1 mutant revealed downregulation of genes associated with chromatin assembly,cell cycle,and male meiosis,correlating with observed meiotic arrest and chromatin condensation defects.These findings highlight the role of PP1 in maize microsporogenesis,and providing more insights into the mechanisms regulating the meiotic progression in maize.展开更多
OBJECTIVE:To investigate the impact of Shenhua tablet(肾华片,SHT)on renal macrophage polarization and renal injury in mice with diabetic kidney disease(DKD)and to explore the potential mechanism involving the hypoxia-...OBJECTIVE:To investigate the impact of Shenhua tablet(肾华片,SHT)on renal macrophage polarization and renal injury in mice with diabetic kidney disease(DKD)and to explore the potential mechanism involving the hypoxia-inducible factor-1α(HIF-1α)and pyruvate kinase M2(PKM2)signaling pathway,along with the glycolysis metabolism pathway.METHODS:The animals were divided into the following groups:Model,Control,dapagliflozin,SHT low-dose,SHT medium-dose,and SHT high-dose.We assessed 24-hour urine protein(24 h-UTP)levels,urinary albuminto-creatinine ratio,and regularly monitored fasting blood glucose during the treatment period.After treatment,we examined renal tissue structure,renal function(urea nitrogen,uric acid,creatinine,cystatin C,β2-microglobulin),and glycolysis in renal macrophages.Additionally,we observed macrophage polarization in renal tissue and measured inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10,monocyte chemoattractant protein-1)to assess the immunoinflammatory status of the renal tissue.Finally,we investigated the expression of the HIF-1α/PKM2 signaling pathway in macrophages to explore its role in the glycolysis process.RESULTS:SHT shows a beneficial effect in treating DKD by reducing 24 h-UTP,regulating blood glucose levels,improving renal tissue structure,protecting renal function,inhibiting macrophage glycolysis,reducing macrophage transformation to the M1 state,and suppressing the expression of the HIF-1α/PKM2 signaling pathway.CONCLUSION:SHT may exert renoprotective effects by inhibiting macrophage glycolysis via the HIF-1α/PKM2 signaling pathway.This inhibition decreases macrophage M1 polarization and reduces immunoinflammatory injury in the renal tissue of DKD mice.展开更多
AIM:To investigate the efficacy of Eleutherine bulbosa(Mill.)Urb.bulb extract(EBE)on the 3D human retinoblastoma cancer cells(WERI-Rb-1)spheroids and explore its apoptotic mechanism.METHODS:The 3D WERI-Rb-1 and human ...AIM:To investigate the efficacy of Eleutherine bulbosa(Mill.)Urb.bulb extract(EBE)on the 3D human retinoblastoma cancer cells(WERI-Rb-1)spheroids and explore its apoptotic mechanism.METHODS:The 3D WERI-Rb-1 and human retinal pigmented epithelium cells(ARPE-19)spheroids were developed using type 1 murine collagen that was excised from the rat tail tendon and cultured via hanging drop and embedded techniques.The cytotoxic activity was examined by Alamar blue assay meanwhile,the morphological characteristics were assessed by 4’,6-diamidino-2-phenylindole(DAPI)and scanning electron microscopy(SEM).The mRNA and protein expressions of apoptotic and antioxidant signal transduction pathways were explored to ascertain its molecular mechanisms.The statistical analysis was carried out using GraphPad Prism.RESULTS:The Alamar blue assay portrayed higher half maximal inhibitory concentration(IC50)values of EBE and cisplatin on 3D WERI-Rb-1 model as compared to the previous study on 2D model.The results of DAPI and SEM illustrated apoptotic features upon treatment with EBE and cisplatin in a dose-dependent manner on 3D WERI-Rb-1 model.The mRNA and protein levels of apoptotic and antioxidant-related pathways were significantly affected by EBE and cisplatin,respectively(P<0.05).The regulation of gene and protein expressions of 3D WERI-Rb-1 spheroids differed from the 2D study,suggesting that the tumor microenvironment of extracellular matrix(ECM)collagen matrix hindered the EBE treatment efficacy,leading to apoptotic evasion.CONCLUSION:A significant inhibition effect of EBE is observed on the 3D WERI-Rb-1 spheroids.The presence of ECM causes an increase in cytotoxic resistance upon treatment with EBE and cisplatin.展开更多
BACKGROUND Helicobacter pylori(H.pylori),a globally prevalent pathogen,is exhibiting increasing rates of antimicrobial resistance.However,clinical implementation of pre-treatment susceptibility testing remains limited...BACKGROUND Helicobacter pylori(H.pylori),a globally prevalent pathogen,is exhibiting increasing rates of antimicrobial resistance.However,clinical implementation of pre-treatment susceptibility testing remains limited due to the organism’s fastidious growth requirements and prolonged culture time.AIM To propose a novel detection method utilizing antibiotic-supplemented media to inhibit susceptible strains,while resistant isolates were identified through urease-mediated hydrolysis of urea,inducing a phenol red color change for visual confirmation.METHODS Colombia agar was supplemented with urea,phenol red,and nickel chloride,and the final pH was adjusted to 7.35.Antibiotic-selective media were prepared by incorporating amoxicillin(0.5μg/mL),clarithromycin(2μg/mL),metronidazole(8μg/mL),or levofloxacin(2μg/mL)into separate batches.Gastric antral biopsies were homogenized and inoculated at 1.0×105 CFU onto the media,and then incubated under microaerobic conditions at 37°C for 28-36 hours.Resistance was determined based on a color change from yellow to pink,and the results were validated via broth microdilution according to Clinical and Laboratory Standards Institute guidelines.RESULTS After 28-36 hours of incubation,the drug-resistant H.pylori isolates induced a light red color change in the medium.Conversely,susceptible strains(H.pylori 26695 and G27)produced no visible color change.Compared with the conventional 11-day protocol,the novel method significantly reduced detection time.Among 201 clinical isolates,182 were successfully evaluated using the new method,resulting in a 90.5%detection rate.This was consistent with the 95.5%agreement rate observed when compared with microdilution-based susceptibility testing.The success rate of the novel approach was significantly higher than that of the comparative method(P<0.01).The accuracy of the new method was comparable to that of the dilution method.CONCLUSION The novel detection method can rapidly detect H.pylori drug resistance within 28-36 hours.With its operational simplicity and high diagnostic performance,it holds strong potential for clinical application in the management of H.pylori antimicrobial resistance.展开更多
Dislocation strengthening,as one of the methods to simultaneously enhance the room temperature strength and ductility of alloys,does not achieve the desired strengthening and plasticity effect during elevated-temperat...Dislocation strengthening,as one of the methods to simultaneously enhance the room temperature strength and ductility of alloys,does not achieve the desired strengthening and plasticity effect during elevated-temperature deformation.Here,we report a novel strategy to boost the dislocation multiplication and accumulation during deformation at elevated temperatures through dynamic strain aging(DSA).With the introduction of the rare-earth element Ho in Mg-Y-Zn alloy,Ho atoms diffuse toward dislocations during deformation at elevated temperatures,provoking the DSA effect,which increases the dislocation density significantly via the interactions of mobile dislocations and Ho atoms.The resulting alloy achieves a great enhancement of dislocation hardening and obtains the dual benefits of high strength and good ductility simultaneously at high homologous temperatures.The present work provides an effective strategy to enhancing the strength and ductility for elevated-temperature materials.展开更多
Mountains serve as exceptional natural laboratories for studying biodiversity due to their heterogeneous landforms and climatic zones.The Himalaya,a global biodiversity hotspot,hosts rich endemic flora,supports vital ...Mountains serve as exceptional natural laboratories for studying biodiversity due to their heterogeneous landforms and climatic zones.The Himalaya,a global biodiversity hotspot,hosts rich endemic flora,supports vital ecosystem functions,and offers a unique window into multifaceted plant diversity patterns.This review synthesizes research on Himalayan plant diversity,including species,phylogenetic,functional,and genetic dimensions,highlighting knowledge gaps and solutions.Research on Himalayan plant diversity has developed significantly.However,gaps remain,especially in studies on phylogenetic and functional diversity.The region's vegetation ranges from tropical rainforests to alpine ecosystems,with species richness typically following a hump-shaped distribution along elevation gradients.The eastern Himalaya exhibits higher plant diversity than the central and western regions.Low-elevation communities were found to be more functionally diverse,whereas high-elevation communities displayed greater ecological specialization.Communities at mid-elevations tend to show greater phylogenetic diversity than those at higher and lower elevations.The eastern and western flanks of the Himalaya retain high levels of genetic diversity and serve as glacial refugia,whereas the central region acts as a hybrid zone for closely related species.Himalayan plant diversity is shaped by historical,climatic,ecological and anthropogenic factors across space and time.However,this rich biodiversity is increasingly threatened by environmental change and growing anthropogenic pressures.Unfortunately,research efforts are constrained by spatial biases and the lack of transnational initiatives and collaborative studies,which could significantly benefit from interdisciplinary approaches,and other coordinated actions.These efforts are vital to safeguarding the Himalayan natural heritage.展开更多
Salinized soil is an important reserved arable land resource in China.The management and utilization of salinized soil can safeguard the current size of arable land and a stable grain yield.Salt accumulation will lead...Salinized soil is an important reserved arable land resource in China.The management and utilization of salinized soil can safeguard the current size of arable land and a stable grain yield.Salt accumulation will lead to the deterioration of soil properties,destroy soil production potential and damage soil ecological functions,which in turn will threaten global water and soil resources and food security,and affect sustainable socio-economic development.Microorganisms are important components of salinized soil.Microbial remediation is an important research tool in improving salinized soil and is key to realizing sustainable development of agriculture and the ecosystem.Knowledge about the impact of salinization on soil properties and measures using microorganisms in remediation of salinized soil has grown over time.However,the mechanisms governing these impacts and the ecological principles for microbial remediation are scarce.Thus,it is imperative to summarize the effects of salinization on soil physical,chemical,and microbial properties,and then review the related mechanisms of halophilic and halotolerant microorganisms in salinized soil remediation via direct and indirect pathways.The stability,persistence,and safety of the microbial remediation effect is also highlighted in this review to further promote the application of microbial remediation in salinized soil.The objective of this review is to provide reference and theoretical support for the improvement and utilization of salinized soil.展开更多
WUSCHEL-related homeobox(WOX)transcription factors play a crucial role in lateral organ development in several plant species;however,their precise functions in soybean(Glycine max[L.]Merr.)were unclear.Here,we identif...WUSCHEL-related homeobox(WOX)transcription factors play a crucial role in lateral organ development in several plant species;however,their precise functions in soybean(Glycine max[L.]Merr.)were unclear.Here,we identified two independent multi-leaflet soybean mutants,mlw48-8 and mlw48-161,from a CRISPR/Cas9-engineered mutant library in the Williams 82 background.Both mutants exhibited irregular leaf margins,and the upper leaves were narrow and almost lanceolate at maturity.Molecular analysis revealed that these are allelic mutants with independent mutations in the WUSCHEL-related homeobox1(GmWOX1A)gene.A transcriptome analysis demonstrated that GmWOX1A modulates the expression of auxin-and leaf development–related genes.Yeast two-hybrid and split-luciferase complementation imaging assays revealed that GmWOX1A interacts with the YABBY family protein GmYAB5,providing further evidence of its potential involvement in leaf development.Notably,the mlw48-161 mutant showed an increased seed number per plant.Consequently,our study not only provides valuable insights into the role of GmWOX1A in soybean leaf development but also offers a potential strategy for high-yield breeding.展开更多
The objective of this study was to address the challenges associated with complex TRPO waste,by utiliz-ing a natural aluminosilicate material to produce glass-ceramic waste forms.When the simulated waste content was b...The objective of this study was to address the challenges associated with complex TRPO waste,by utiliz-ing a natural aluminosilicate material to produce glass-ceramic waste forms.When the simulated waste content was below 30 wt.%,glassy waste forms were successfully obtained.Ce and Fe played crucial roles in the formation of Si-O-Ce bonds and[FeO_(4)]-tetrahedra in the glass network,which effectively immo-bilized other waste elements.However,when the waste content exceeded 30 wt.%,the waste was incor-porated into feldspar,iron-manganese crystals,fluorite ceramic,and glass.This combination of ceramic and glass matrices synergistically immobilized the waste,resulting in excellent mechanical performance and chemical durability.The leaching rates of LR_(Ce)and LR_(Nd)were remarkably low around-10^(−6)to 10^(−7)g m^(−2)d^(−1),after 42 d.Furthermore,the study also investigated the role of multi-valence elements,such as Ce,Fe,and Mn,in the formation of iron-containing aluminosilicate glass-ceramics.The findings offer a novel approach to effectively immobilize complex nuclear waste.展开更多
Cyclic impact induces ongoing fatigue damage and performance degradation in anchoring structures,ser-ving as a critical factor leading to the instability of deep roadways.This paper takes the intrinsic spatio-temporal...Cyclic impact induces ongoing fatigue damage and performance degradation in anchoring structures,ser-ving as a critical factor leading to the instability of deep roadways.This paper takes the intrinsic spatio-temporal relationship of macro-microscopic cumulative damage in anchoring structures as the main thread,revealing the mechanism of bearing capacity degradation and progressive instability of anchoring structure under cyclic impact.Firstly,a set of impact test devices and methods for the prestressed solid anchor bolt anchoring structure were developed,effectively replicating the cyclic impact stress paths in situ.Secondly,cyclic impact anchoring structure tests and simulations were conducted,which clarifies the damage evolution mechanism of the anchoring structure.Prestress loss follows a cubic decay func-tion as the number of impacts increases.Under the same impact energy and pretension force,the impact resistance cycles of extended anchoring and full-length anchoring were increased by 186.7%and 280%,respectively,compared to end anchoring.The rate of internal damage accumulation is positively corre-lated with impact energy and negatively correlated with anchorage length.Internal tensile cracks account for approximately 85%.Stress transmission follows a fluctuating pattern.Compared to the extended anchoring,the maximum vibration velocity of the exposed end particles in the full-length anchoring was reduced by 59.31%.Damage evolution exhibits a pronounced cumulative mutation effect.Then,a three-media,two-interface mechanical model of the anchoring structure was constructed.It has been clarified that the compressive stress,tensile stress,and oscillation effect arising from rapid transi-tions between compression and tension are the primary internal factors responsible for the degradation of the anchoring structure’s bearing capacity.Finally,the progressive instability mechanism of the anchoring structure under cyclic impact was elucidated.The mutual feedback and superposition of media rupture,interface debonding,and bearing capacity degradation result in overall failure.The failure pro-cess involves stages dominated by oscillation-compression,tensile stress,and compression failure.A tar-geted control strategy was further proposed.This provides a reference for maintaining the long-term stability of deep roadways under dynamic impact loads.展开更多
Electrochemical sensing provides a powerful technological means for the therapeutic drug monitoring of drug-resistant tuberculosis but requires a functionalized electrode to capture the analytes and catalyze their red...Electrochemical sensing provides a powerful technological means for the therapeutic drug monitoring of drug-resistant tuberculosis but requires a functionalized electrode to capture the analytes and catalyze their redox reactions.Herein,we construct a nickel-tannic acid supramolecular network(Ni-TA)on the surface of electrospun-derived C-CeO_(2) nanofiber for the sensitive and simultaneous detection of isoniazid(INZ)and hydrazine(HYD).Mechanistic investigations demonstrate that Ni-TA is electronegative and hydrophilic,thus facilitating an efficient mass and electron transfer.Ni-TA/C-CeO_(2) has higher adsorption rate constants(0.091 g mg^(-1)h^(-1)for INZ,and 0.062 g mg^(-1)h^(-1)for HYD)than native C-CeO_(2)(0.075 g mg^(-1)h^(-1)for INZ,and 0.047 g mg^(-1)h^(-1)for HYD).Moreover,Ni-TA/C-CeO_(2)(56Ω)has lower charge transfer resistances than C-CeO_(2)(417Ω).Ni-TA/C-CeO_(2) performs low detection limits and wide linearity ranges for INZ(0.012μmol/L and 0.1-400μmol/L,respectively)and HYD(0.008μmol/L and 0.015-1420μmol/L,respectively),coupled with high selectivity,cycle stability and reproducibility.This research demonstrated the promising applications of Ni-TA/C-CeO_(2) by analyzing human-collected plasma and urine samples.展开更多
In the realm of autoimmune and inflammatory diseases,the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway has been thoroughly investigated and established.Despite this,the clinical a...In the realm of autoimmune and inflammatory diseases,the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway has been thoroughly investigated and established.Despite this,the clinical approval of drugs targeting the cGAS-STING pathway has been limited.The Total glucosides of paeony(TGP)is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis(RA),emerged as a subject of our study.We found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway,triggered by various cGAS-STING agonists,in mouse bone marrow-derived macrophages(BMDMs)and Tohoku Hospital Pediatrics-1(THP-1)cells.This inhibition was noted alongside the suppression of interferon regulatory factor 3(IRF3)phosphorylation and the expression of interferon-beta(IFN-β),C-X-C motif chemokine ligand 10(CXCL10),and inflammatory mediators such as tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6).The mechanism of action appeared to involve the TGP’s attenuation of the STING-IRF3 interaction,without affecting STING oligomerization,thereby inhibiting the activation of downstream signaling pathways.In vivo,the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid(DMXAA)and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway,offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway.展开更多
Recently,immunotherapy has redefined cancer treatment by promoting the rapid killing of tumor cells through the immune system.Herbal medicines have been increasingly used as adjunct therapies to complement cancer trea...Recently,immunotherapy has redefined cancer treatment by promoting the rapid killing of tumor cells through the immune system.Herbal medicines have been increasingly used as adjunct therapies to complement cancer treatment along with chemotherapy and radiotherapy to delay tumor development,reduce pain,and prolong patient survival.However,the potential immunotherapeutic effects of these herbal derivatives are limited by their structural instability,poor membrane permeability,and low bioavailability.To address this issue,nanotechnology has been used to enhance the activity of active compounds.Therefore,this review focuses on the effectiveness of the active ingredients of herbal medicines in suppressing tumor progression by modulating both the innate and adaptive immune systems,challenges in their delivery,and the application of nanocarriers for the effective delivery of these herbal components.展开更多
To understand the temporal and spatial variations in nutrient dynamics,as well as the potential cross-shelf transport of nutrients between the East China Sea(ECS)shelf and the northwestern Pacific Ocean,six field obse...To understand the temporal and spatial variations in nutrient dynamics,as well as the potential cross-shelf transport of nutrients between the East China Sea(ECS)shelf and the northwestern Pacific Ocean,six field observations covering the ECS were conducted in spring,summer,and autumn in 2011 and 2013.Nutrient dynamics in the ECS and nutrient exchange between shelf water and the open ocean were examined.High concentrations of dissolved inorganic nutrients were detected in the nearshore surface layer and offshore bottom layer in different seasons,and the concentrations of dissolved inorganic nutrients in surface seawater were lower in summer and autumn than in spring.The concentrations of dissolved organic nutrients in Kuroshio surface water were slightly lower in summer than in spring,but the concentrations in Kuroshio subsurface water were slightly higher in summer than in spring.There were abundant nutrient reservoirs in the euphotic zone of the ECS,which explained the high primary productivity.The evaluation of cross-shelf transport indicated that nutrients from shelf water were transported out across the 200 m isobath through the surface layer with the density(σ)less than 23.0 kg/m^(3) in spring.The flux of dissolved inorganic nitrogen transported from the ECS shelf to the Northwest Pacific Ocean in spring was equivalent to 21%of the atmospheric nitrogen deposition in the Northwest Pacific Ocean.In summer,the onshore flux in the surface and bottom layers accounted for 80%of the total flux,and the transportation of nutrients along the surface layer to the continental shelf contributed to the nutrient storage and primary productivity of the euphotic zone in the ECS shelf in summer.展开更多
The rotator cuff tear has emerged as a significant global health concern.However,existing therapies fail to fully restore the intricate bone-to-tendon gradients,resulting in compromised biomechanical functionalities o...The rotator cuff tear has emerged as a significant global health concern.However,existing therapies fail to fully restore the intricate bone-to-tendon gradients,resulting in compromised biomechanical functionalities of the reconstructed enthesis tissues.Herein,a tri-layered core–shell microfibrous scaffold with layer-specific growth factors(GFs)release is developed using coaxial electrohydrodynamic(EHD)printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair.Stromal cell-derived factor-1(SDF-1)is loaded in the shell,while basic fibroblast GF,transforming GF-beta,and bone morphogenetic protein-2 are loaded in the core of the EHD-printed microfibrous scaffolds in a layer-specific manner.Correspondingly,the tri-layered microfibrous scaffolds have a core–shell fiber size of(25.7±5.1)μm,with a pore size sequentially increasing from(81.5±4.6)μm to(173.3±6.9)μm,and to(388.9±6.9μm)for the tenogenic,chondrogenic,and osteogenic instructive layers.A rapid release of embedded GFs is observed within the first 2 d,followed by a faster release of SDF-1 and a slightly slower release of differentiation GFs for approximately four weeks.The coaxial EHD-printed microfibrous scaffolds significantly promote stem cell recruitment and direct their differentiation toward tenocyte,chondrocyte,and osteocyte phenotypes in vitro.When implanted in vivo,the tri-layered core–shell microfibrous scaffolds rapidly restored the biomechanical functions and promoted enthesis tissue regeneration with native-like bone-to-tendon gradients.Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration.展开更多
文摘Background:Colorectal cancer(CRC)has become one of the major life-threatening complications in patients with inflammatory bowel disease(IBD),which includes ulcerative colitis(UC)and Crohn's disease(CD).This study aimed to explore the clinicalpathologic similarities and differences in the IBD-associ吐ed CRC(IBD-CRC)between patients in China and Canada.Methods:Data of 78 patients with IBD-CRC retrospectively retrieved from two representative medical institutions in Beijing(China)and Calgary(Canada)over the same past 13 years,including 25(22 UC-associated and three CD-associated)from Beijing group and 53(32 UC-associated and 21 CD-associated)from Calgary group,were compared with regards to their clinical and pathologic characteristics.Results:Several known features of IBD-CRC were seen in both groups,including long duration and large extent of colitis,active inflammation background,multifocal lesions,and advanced tumor-node-metastasis stage.Beijing group showed a significantly higher percentage of UC(88.0%vs.60.4%,P=0.018),younger age at diagnosis of CRC(48.6±12.8 years vs.61.6±14.7 years,P<0.001),lower ratio of mucinous adenocarcinoma(7.1%us.42.4%,P=0.001)compared with Calgary group.None of the Beijing group had concurrent primary sclerosing cholangitis,while 5.7%of Calgary group did.Surveillance colonoscopy favored the detection rate of precancerous lesions(41.4%vs.17.0%,P=0.002).Conclusions:As compared with patients from the Calgary group,the IBD-CRC patients in Beijing group were younger,less CDassociated and had less mucinous features,otherwise they were similar in many common features.
基金sponsored by the National Natural Science Foundation of China(Nos.U23A6005 and 22178069)。
文摘Zn-air battery(ZAB)has garnered significant attention owing to its environmental friendliness and safety attributes.A critical challenge in advancing ZAB technology lies in the development of high-performance and cost-effective electrocatalysts for oxygen redox reactions(OER and ORR).Herein,we report Co/Fe carbon-supported composites as efficient bifunctional catalyst encapsulated in oxidative ammonolysis modified lignin-derived N-doped biochar(Co Fe-Co_(x)N@NOALC).It exhibited exceptional electrochemical performance in aqueous ZAB owing to their uniform dispersed and small particle size,with a peak power density of 154 mW/cm^(2)and a specific capacity of 770 mAh/g.Most notably,it exhibited a long cycle stability,surpassing 1500 h at a current density of 10 mA/cm^(2),with a mere 11.4%decrease in the chargedischarge efficiency of the battery.This study proposes a viable strategy for enhancing the performance and reducing the cost of Zn-air batteries through the utilization of biomass-derived materials.
基金supported by the National Key Research and Development Program of China(Nos.2021YFC2400600,2022YFE0203600)National Natural Science Foundation of China(Nos.81925035,82304842,82204628)+6 种基金High-level Innovative Research Institute(No.2021B0909050003)Chinese Academy of Sciences President’s International Fellowship Initiative(No.2024VBB0004)the Scientific and Technological Innovation Projects in Zhongshan City(Nos.LJ2021001,CXTD2022011)the Social Welfare and Basic Research Projects in Zhongshan(No.221014134359625)the Special Projects in Key Areas of Colleges and Universities in Guangdong Province(No.2022ZDZX2015)the Science and Technology Program of Guangzhou(No.2024A04J4899)Young Talent Project of Guangzhou University of Chinese Medicine(No.A1–2601–24–414–110Z76)。
文摘Rheumatoid arthritis(RA)is a refractory autoimmune disease with limited treatment options.Plantderived exosomes-like nanovesicles(PDENs)have emerged as a novel nanomedical approach,with the inherent bioactive compounds from their source plants.The roots of Morinda officinalis How.(MO),a Chinese herb,exhibit notable anti-inflammatory activities and hold promising therapeutic value.We engineered a joint-targe ting delivery system(termed MOE@EM)by masking MO-derived exosomes-like nanovesicles(MOE)with erythrocyte membrane(EM).This biomimetic strategy,using EM camouflage,is intended to improve the in vivo fate of MOE.We investigated the antioxidative and anti-inflammatory activities,immunogenicity,drug accumulation in the joint,and therapeutic efficacy to ascertain its suitability for RA therapy.UV irradiation significantly increased the activities of catalase and peroxidase of MOE,and enhanced the anti-inflammatory effects via the Wnt/β-catenin pathway.Furthermore,MOE@EM markedly attenuated dendritic cell activation.MOE@EM exhibited joint-specific delivery,with substantial reduction in paw swelling,and favorable modulation of immune microenvironment.
基金Supported by the Excellent Youth Project of Anhui Universities,No.2022AH030065National Natural Science Foundation of China,No.82474224 and No.82405244+3 种基金Anhui Provincial Natural Science Foundation,No.2408085MH223Open Projects of Anhui Province Key Laboratory of Meridian Viscera Correlationship,No.2024AHMVC04Research Project of Xin’an Medical and Chinese Medicine Modernization Research Institute,No.2023CXMMTCM016the Anhui Province Scientific Research Planning Project,No.2022AH050438.
文摘BACKGROUND Visceral hypersensitivity is the core pathogenesis of irritable bowel syndrome(IBS)and is often accompanied by negative emotions such as anxiety or depression.Paraventricular hypothalamic nucleus(PVN)corticotropin-releasing factor(CRF)is involved in the stress-related gastrointestinal dysfunction.Electroacupuncture(EA)has unique advantages for the treatment of visceral hypersensitivity and negative emotions in IBS patients.However,the underlying mechanisms remain unclear.AIM To investigate the pathological mechanisms visceral hypersensitivity and negative emotions in IBS,as well as the effect mechanism of EA.METHODS A model of diarrhoeal IBS(IBS-D)with negative emotions was prepared by chronic restraint combined with glacial acetic acid enema.The effect of EA was verified by abdominal withdrawal reflex and open-field test.PVN CRFcolonic mast cell(MC)/transient potential receptor vanilloid type 1(TRPV1)pathway was detected by immunofluorescence,Western blot,ELISA,and toluidine blue staining.Moreover,PVN CRFergic neurons were activated or inhibited by chemogenetical technique to observe the changes of effect indicator.RESULTS In the model group,IBS-D symptoms and negative emotions were successfully induced.Notably,the combination of Baihui(GV20)with Tianshu(ST25)and Dachangshu(BL25)acupoints showed the greatest efficacy in improving the negative emotions and visceral hypersensitivity in model mice.Furthermore,we found that EA inhibited overactivated PVN CRFergic neurons and the overexpression of serum CRF,colonic CRF,CRF-receptor 1(CRFR1),mast cell tryptase(MCT),protease-activated receptor 2 and TRPV1 in model mice.Moreover,we found that activating PVN CRFergic neurons induced negative emotions and visceral hypersensitivity in normal mice;however,inhibiting PVN CRFergic neurons alleviated negative emotions and intestinal symptoms in model mice and decreased the expression of colonic CRF-R1,MCT,and TRPV1.CONCLUSION This research highlights the key role of PVN CRF-MC CRF-R1 and the downstream MC/TRPV1 pathway in the pathological process of IBS-D and the mechanism of the effect of EA.
基金co-supported by Basic and Applied Basic Research Foundation of Guangdong Province(No.2022A1515110622)Natural Science Basic Research Program of Shaanxi Province(No.2023-JC-QN-0548)+1 种基金National Key R&D Program of China(No.2022YFB3402200)the Fundamental Research Funds for the Central Universities。
文摘This study presents new methods to effectively model the anisotropic yielding and hardening behavior of laser powder bed fusion fabricated aluminum alloy under both monotonic and cyclic loading conditions.The proposed model combines the yield surface-interpolation method to accurately describe the anisotropic hardening rates in various directions,with the Chaboche kinematic hardening rule to precisely reflect the cyclic characteristics.For numerical implementation of the combined anisotropic and cyclic constitutive model,a fully implicit stress integration algorithm based on return mapping method is provided.Moreover,the multiple parameters associated with the model are categorized and identified in an uncoupled manner.The isotropic and cyclic hardening parameters are determined by an inverse method,and the stability of the optimization outcomes is validated by applying different starting points for the parameters.Particularly,the back-stress effect on the identification of anisotropic parameters associated with the stress invariant-based Hill48 yield function is considered for the first time.This consideration leads to an improved prediction accuracy compared to the identification of anisotropic parameters without considering back-stress effect.The combined anisotropic and cyclic constitutive model,along with the calibrated parameters,are proven capable of accurately reproducing the intricate deformation behavior of laser powder bed fusion fabricated AlSi10Mg.
基金supported by National Key Research and Development Program of China(2022YFF1003501)Biological BreedingMajor Projects(2023ZD04076)+1 种基金Funds from State Key Laboratory of Maize Bio-breeding(SKLMB2404,SKLMB2440)Anhui Natural Science Foundation(2308085QC92).
文摘Meiosis,a critical process for sexual reproduction,requires precise regulation to ensure the correct progression of meiotic stages.In yeast and animals,errors in meiotic recombination and homologous chromosomes synapsis bring a surveillance mechanism named pachytene checkpoint to prevent pachytene exit.However,most plant mutants with defects in meiotic prophase I continue cell cycle progression,which hindered the characterization of factors controlling the prophase I to metaphase I transition.Here,we characterized a male-sterile mutant in maize,prolonged prophase1(pp1),which exhibited pachytene and diakinesis arrest in male meiosis,and abnormal chromatin condensation.Using mapbased cloning,the PP1 gene was isolated as a PHD family transcription factor,and its transcripts of PP1 were preferentially accumulated in tapetum and male germline cells during microsporogenesis.Transcriptomic analysis of the pp1 mutant revealed downregulation of genes associated with chromatin assembly,cell cycle,and male meiosis,correlating with observed meiotic arrest and chromatin condensation defects.These findings highlight the role of PP1 in maize microsporogenesis,and providing more insights into the mechanisms regulating the meiotic progression in maize.
基金National Natural Science Foundation of China:Basic Research on the Mechanism of Organ Immune Damage and the Diagnosis and Treatment of Integrated Traditional Chinese and Western Medicine(No.32141005)。
文摘OBJECTIVE:To investigate the impact of Shenhua tablet(肾华片,SHT)on renal macrophage polarization and renal injury in mice with diabetic kidney disease(DKD)and to explore the potential mechanism involving the hypoxia-inducible factor-1α(HIF-1α)and pyruvate kinase M2(PKM2)signaling pathway,along with the glycolysis metabolism pathway.METHODS:The animals were divided into the following groups:Model,Control,dapagliflozin,SHT low-dose,SHT medium-dose,and SHT high-dose.We assessed 24-hour urine protein(24 h-UTP)levels,urinary albuminto-creatinine ratio,and regularly monitored fasting blood glucose during the treatment period.After treatment,we examined renal tissue structure,renal function(urea nitrogen,uric acid,creatinine,cystatin C,β2-microglobulin),and glycolysis in renal macrophages.Additionally,we observed macrophage polarization in renal tissue and measured inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10,monocyte chemoattractant protein-1)to assess the immunoinflammatory status of the renal tissue.Finally,we investigated the expression of the HIF-1α/PKM2 signaling pathway in macrophages to explore its role in the glycolysis process.RESULTS:SHT shows a beneficial effect in treating DKD by reducing 24 h-UTP,regulating blood glucose levels,improving renal tissue structure,protecting renal function,inhibiting macrophage glycolysis,reducing macrophage transformation to the M1 state,and suppressing the expression of the HIF-1α/PKM2 signaling pathway.CONCLUSION:SHT may exert renoprotective effects by inhibiting macrophage glycolysis via the HIF-1α/PKM2 signaling pathway.This inhibition decreases macrophage M1 polarization and reduces immunoinflammatory injury in the renal tissue of DKD mice.
基金Supported by Universiti Putra Malaysia,Serdang,Selangor,Malaysia(UPM/700-2/1/GPB/2017/9549900).
文摘AIM:To investigate the efficacy of Eleutherine bulbosa(Mill.)Urb.bulb extract(EBE)on the 3D human retinoblastoma cancer cells(WERI-Rb-1)spheroids and explore its apoptotic mechanism.METHODS:The 3D WERI-Rb-1 and human retinal pigmented epithelium cells(ARPE-19)spheroids were developed using type 1 murine collagen that was excised from the rat tail tendon and cultured via hanging drop and embedded techniques.The cytotoxic activity was examined by Alamar blue assay meanwhile,the morphological characteristics were assessed by 4’,6-diamidino-2-phenylindole(DAPI)and scanning electron microscopy(SEM).The mRNA and protein expressions of apoptotic and antioxidant signal transduction pathways were explored to ascertain its molecular mechanisms.The statistical analysis was carried out using GraphPad Prism.RESULTS:The Alamar blue assay portrayed higher half maximal inhibitory concentration(IC50)values of EBE and cisplatin on 3D WERI-Rb-1 model as compared to the previous study on 2D model.The results of DAPI and SEM illustrated apoptotic features upon treatment with EBE and cisplatin in a dose-dependent manner on 3D WERI-Rb-1 model.The mRNA and protein levels of apoptotic and antioxidant-related pathways were significantly affected by EBE and cisplatin,respectively(P<0.05).The regulation of gene and protein expressions of 3D WERI-Rb-1 spheroids differed from the 2D study,suggesting that the tumor microenvironment of extracellular matrix(ECM)collagen matrix hindered the EBE treatment efficacy,leading to apoptotic evasion.CONCLUSION:A significant inhibition effect of EBE is observed on the 3D WERI-Rb-1 spheroids.The presence of ECM causes an increase in cytotoxic resistance upon treatment with EBE and cisplatin.
基金Supported by the Guangxi Science and Technology Major Projects,No.AA23073012the National Natural Science Foundation of China,No.32360035 and No.32060018。
文摘BACKGROUND Helicobacter pylori(H.pylori),a globally prevalent pathogen,is exhibiting increasing rates of antimicrobial resistance.However,clinical implementation of pre-treatment susceptibility testing remains limited due to the organism’s fastidious growth requirements and prolonged culture time.AIM To propose a novel detection method utilizing antibiotic-supplemented media to inhibit susceptible strains,while resistant isolates were identified through urease-mediated hydrolysis of urea,inducing a phenol red color change for visual confirmation.METHODS Colombia agar was supplemented with urea,phenol red,and nickel chloride,and the final pH was adjusted to 7.35.Antibiotic-selective media were prepared by incorporating amoxicillin(0.5μg/mL),clarithromycin(2μg/mL),metronidazole(8μg/mL),or levofloxacin(2μg/mL)into separate batches.Gastric antral biopsies were homogenized and inoculated at 1.0×105 CFU onto the media,and then incubated under microaerobic conditions at 37°C for 28-36 hours.Resistance was determined based on a color change from yellow to pink,and the results were validated via broth microdilution according to Clinical and Laboratory Standards Institute guidelines.RESULTS After 28-36 hours of incubation,the drug-resistant H.pylori isolates induced a light red color change in the medium.Conversely,susceptible strains(H.pylori 26695 and G27)produced no visible color change.Compared with the conventional 11-day protocol,the novel method significantly reduced detection time.Among 201 clinical isolates,182 were successfully evaluated using the new method,resulting in a 90.5%detection rate.This was consistent with the 95.5%agreement rate observed when compared with microdilution-based susceptibility testing.The success rate of the novel approach was significantly higher than that of the comparative method(P<0.01).The accuracy of the new method was comparable to that of the dilution method.CONCLUSION The novel detection method can rapidly detect H.pylori drug resistance within 28-36 hours.With its operational simplicity and high diagnostic performance,it holds strong potential for clinical application in the management of H.pylori antimicrobial resistance.
基金supported by the National Key Research and Development Project(2023YFA1609100)the NSFC Funding(U2141207,52171111,52001083)+6 种基金Natural Science Foundation of Heilongjiang(YQ2023E026)China Postdoctoral Science foundation(2024M754149)Postdoctoral Fellowship Program of CPSF(GZC20242192)support from the National Science Foundation(DMR-1611180 and 1809640)with the program directors,DrsHKU Seed Fund for Collaborative Research(#2207101618)support by Croucher Senior Research Fellowship and City U Project(Project No.9229019)Shenzhen Science and Technology Program(Project No.JCYJ20220818101203007)。
文摘Dislocation strengthening,as one of the methods to simultaneously enhance the room temperature strength and ductility of alloys,does not achieve the desired strengthening and plasticity effect during elevated-temperature deformation.Here,we report a novel strategy to boost the dislocation multiplication and accumulation during deformation at elevated temperatures through dynamic strain aging(DSA).With the introduction of the rare-earth element Ho in Mg-Y-Zn alloy,Ho atoms diffuse toward dislocations during deformation at elevated temperatures,provoking the DSA effect,which increases the dislocation density significantly via the interactions of mobile dislocations and Ho atoms.The resulting alloy achieves a great enhancement of dislocation hardening and obtains the dual benefits of high strength and good ductility simultaneously at high homologous temperatures.The present work provides an effective strategy to enhancing the strength and ductility for elevated-temperature materials.
基金funded by the Key Research Program of Frontier Sciences,CAS(ZDBS-LY-7001)the National Natural Science Foundation of China(32170398,42211540718,W2433074,32071541)+6 种基金the CAS“Light of West China”Programthe Xingdian Talent Support Program of Yunnan Province(XDYC-QNRC-2022-0026)the Natural Science Foundation of Yunnan(202201AT070222)the Fund of Yunnan Key Laboratory of Crop Wild Relatives Omics(CWR-2024-04)funding from the China Scholarship Council(202304910135,202304910138)for their oneyear study at the University of Toronto,Canadathe Pakistan Science Foundation&NSFC for the joint venture under the project(PSF-NSFC/JSEP/BIO/COAU(04))surpported by the Innovation Program of Shanghai Municipal Education Commission(2023ZKZD36).
文摘Mountains serve as exceptional natural laboratories for studying biodiversity due to their heterogeneous landforms and climatic zones.The Himalaya,a global biodiversity hotspot,hosts rich endemic flora,supports vital ecosystem functions,and offers a unique window into multifaceted plant diversity patterns.This review synthesizes research on Himalayan plant diversity,including species,phylogenetic,functional,and genetic dimensions,highlighting knowledge gaps and solutions.Research on Himalayan plant diversity has developed significantly.However,gaps remain,especially in studies on phylogenetic and functional diversity.The region's vegetation ranges from tropical rainforests to alpine ecosystems,with species richness typically following a hump-shaped distribution along elevation gradients.The eastern Himalaya exhibits higher plant diversity than the central and western regions.Low-elevation communities were found to be more functionally diverse,whereas high-elevation communities displayed greater ecological specialization.Communities at mid-elevations tend to show greater phylogenetic diversity than those at higher and lower elevations.The eastern and western flanks of the Himalaya retain high levels of genetic diversity and serve as glacial refugia,whereas the central region acts as a hybrid zone for closely related species.Himalayan plant diversity is shaped by historical,climatic,ecological and anthropogenic factors across space and time.However,this rich biodiversity is increasingly threatened by environmental change and growing anthropogenic pressures.Unfortunately,research efforts are constrained by spatial biases and the lack of transnational initiatives and collaborative studies,which could significantly benefit from interdisciplinary approaches,and other coordinated actions.These efforts are vital to safeguarding the Himalayan natural heritage.
基金the National Natural Science Foundation of China(No.42107513)the Key Projects of Natural Science Foundation of Gansu Province(No.22JR5RA051)+1 种基金the Gansu Province Science and Technology project(No.21JR7RA070)the Key Research and Development Program of Gansu Province(No.21YF5FA151).
文摘Salinized soil is an important reserved arable land resource in China.The management and utilization of salinized soil can safeguard the current size of arable land and a stable grain yield.Salt accumulation will lead to the deterioration of soil properties,destroy soil production potential and damage soil ecological functions,which in turn will threaten global water and soil resources and food security,and affect sustainable socio-economic development.Microorganisms are important components of salinized soil.Microbial remediation is an important research tool in improving salinized soil and is key to realizing sustainable development of agriculture and the ecosystem.Knowledge about the impact of salinization on soil properties and measures using microorganisms in remediation of salinized soil has grown over time.However,the mechanisms governing these impacts and the ecological principles for microbial remediation are scarce.Thus,it is imperative to summarize the effects of salinization on soil physical,chemical,and microbial properties,and then review the related mechanisms of halophilic and halotolerant microorganisms in salinized soil remediation via direct and indirect pathways.The stability,persistence,and safety of the microbial remediation effect is also highlighted in this review to further promote the application of microbial remediation in salinized soil.The objective of this review is to provide reference and theoretical support for the improvement and utilization of salinized soil.
基金supported by the Major Project of National Agricultural Science and Technology of China,the National Natural Science Foundation of China (32171965,32072091,31271750)the Core Technology Development for Breeding Program of Jiangsu Province (JBGS-2021-014)Collaborative Innovation Center for Modern Crop Production Co-sponsored by Province and Ministry (CIC-MCP)Program.
文摘WUSCHEL-related homeobox(WOX)transcription factors play a crucial role in lateral organ development in several plant species;however,their precise functions in soybean(Glycine max[L.]Merr.)were unclear.Here,we identified two independent multi-leaflet soybean mutants,mlw48-8 and mlw48-161,from a CRISPR/Cas9-engineered mutant library in the Williams 82 background.Both mutants exhibited irregular leaf margins,and the upper leaves were narrow and almost lanceolate at maturity.Molecular analysis revealed that these are allelic mutants with independent mutations in the WUSCHEL-related homeobox1(GmWOX1A)gene.A transcriptome analysis demonstrated that GmWOX1A modulates the expression of auxin-and leaf development–related genes.Yeast two-hybrid and split-luciferase complementation imaging assays revealed that GmWOX1A interacts with the YABBY family protein GmYAB5,providing further evidence of its potential involvement in leaf development.Notably,the mlw48-161 mutant showed an increased seed number per plant.Consequently,our study not only provides valuable insights into the role of GmWOX1A in soybean leaf development but also offers a potential strategy for high-yield breeding.
基金supported by the National Natural Science Foundation of China(Nos.21976146 and U2167221)the Project of State Key Laboratory of Environment-friendly Energy Materials,Southwest University of Science and Technology(No.23fksy10)+2 种基金the Open Foundation of Nuclear Medicine Laboratory of Mianyang Central Hospital(No.2021HYX028)the Sichuan Science and Technology Program(No.2023NSFSC0353)the Applied Basic Research Project of Science and Technology Department of Sichuan Province(No.2022NSFSC1197)。
文摘The objective of this study was to address the challenges associated with complex TRPO waste,by utiliz-ing a natural aluminosilicate material to produce glass-ceramic waste forms.When the simulated waste content was below 30 wt.%,glassy waste forms were successfully obtained.Ce and Fe played crucial roles in the formation of Si-O-Ce bonds and[FeO_(4)]-tetrahedra in the glass network,which effectively immo-bilized other waste elements.However,when the waste content exceeded 30 wt.%,the waste was incor-porated into feldspar,iron-manganese crystals,fluorite ceramic,and glass.This combination of ceramic and glass matrices synergistically immobilized the waste,resulting in excellent mechanical performance and chemical durability.The leaching rates of LR_(Ce)and LR_(Nd)were remarkably low around-10^(−6)to 10^(−7)g m^(−2)d^(−1),after 42 d.Furthermore,the study also investigated the role of multi-valence elements,such as Ce,Fe,and Mn,in the formation of iron-containing aluminosilicate glass-ceramics.The findings offer a novel approach to effectively immobilize complex nuclear waste.
基金supported by National Key Research and Development Program of China(No.2023YFC2907600)the National Natural Science Foundation of China(Nos.52074263,52274145 and 52034007)+1 种基金the Postdoctoral Fellowship Program(Grade C)of China Postdoctoral Science Foundation(No.GZC20241925)the Fundamental Research Funds for the Central Universities(No.2024QN11002).
文摘Cyclic impact induces ongoing fatigue damage and performance degradation in anchoring structures,ser-ving as a critical factor leading to the instability of deep roadways.This paper takes the intrinsic spatio-temporal relationship of macro-microscopic cumulative damage in anchoring structures as the main thread,revealing the mechanism of bearing capacity degradation and progressive instability of anchoring structure under cyclic impact.Firstly,a set of impact test devices and methods for the prestressed solid anchor bolt anchoring structure were developed,effectively replicating the cyclic impact stress paths in situ.Secondly,cyclic impact anchoring structure tests and simulations were conducted,which clarifies the damage evolution mechanism of the anchoring structure.Prestress loss follows a cubic decay func-tion as the number of impacts increases.Under the same impact energy and pretension force,the impact resistance cycles of extended anchoring and full-length anchoring were increased by 186.7%and 280%,respectively,compared to end anchoring.The rate of internal damage accumulation is positively corre-lated with impact energy and negatively correlated with anchorage length.Internal tensile cracks account for approximately 85%.Stress transmission follows a fluctuating pattern.Compared to the extended anchoring,the maximum vibration velocity of the exposed end particles in the full-length anchoring was reduced by 59.31%.Damage evolution exhibits a pronounced cumulative mutation effect.Then,a three-media,two-interface mechanical model of the anchoring structure was constructed.It has been clarified that the compressive stress,tensile stress,and oscillation effect arising from rapid transi-tions between compression and tension are the primary internal factors responsible for the degradation of the anchoring structure’s bearing capacity.Finally,the progressive instability mechanism of the anchoring structure under cyclic impact was elucidated.The mutual feedback and superposition of media rupture,interface debonding,and bearing capacity degradation result in overall failure.The failure pro-cess involves stages dominated by oscillation-compression,tensile stress,and compression failure.A tar-geted control strategy was further proposed.This provides a reference for maintaining the long-term stability of deep roadways under dynamic impact loads.
基金supported by Cooperative Education Program of the Ministry of Education,China(Nos.202101256027 and 202102070134)National Excellent Young Scientists Found(No.00308054A1045)+3 种基金National Key R&D Program of China(No.2022YFA0912800)National Natural Science Foundation of China(No.22178233)Talents Program of Sichuan Province,Double First Class University Plan of Sichuan University,State Key Laboratory of Polymer Materials Engineering(No.sklpme 2020-03-01)Sichuan Tianfu Emei Project(No.2022-EC02-00073-CG)。
文摘Electrochemical sensing provides a powerful technological means for the therapeutic drug monitoring of drug-resistant tuberculosis but requires a functionalized electrode to capture the analytes and catalyze their redox reactions.Herein,we construct a nickel-tannic acid supramolecular network(Ni-TA)on the surface of electrospun-derived C-CeO_(2) nanofiber for the sensitive and simultaneous detection of isoniazid(INZ)and hydrazine(HYD).Mechanistic investigations demonstrate that Ni-TA is electronegative and hydrophilic,thus facilitating an efficient mass and electron transfer.Ni-TA/C-CeO_(2) has higher adsorption rate constants(0.091 g mg^(-1)h^(-1)for INZ,and 0.062 g mg^(-1)h^(-1)for HYD)than native C-CeO_(2)(0.075 g mg^(-1)h^(-1)for INZ,and 0.047 g mg^(-1)h^(-1)for HYD).Moreover,Ni-TA/C-CeO_(2)(56Ω)has lower charge transfer resistances than C-CeO_(2)(417Ω).Ni-TA/C-CeO_(2) performs low detection limits and wide linearity ranges for INZ(0.012μmol/L and 0.1-400μmol/L,respectively)and HYD(0.008μmol/L and 0.015-1420μmol/L,respectively),coupled with high selectivity,cycle stability and reproducibility.This research demonstrated the promising applications of Ni-TA/C-CeO_(2) by analyzing human-collected plasma and urine samples.
基金This work was supported by the Natural Science Foundation of Beijing(No.7232321)the Cultivating and Improving the Service Ability of Traditional Chinese Medicine(No.2021ZY038)+1 种基金the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(No.ZYYCXTD-C-202005)the State Key Program of National Natural Science of China(Nos.81930110,82230118)。
文摘In the realm of autoimmune and inflammatory diseases,the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway has been thoroughly investigated and established.Despite this,the clinical approval of drugs targeting the cGAS-STING pathway has been limited.The Total glucosides of paeony(TGP)is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis(RA),emerged as a subject of our study.We found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway,triggered by various cGAS-STING agonists,in mouse bone marrow-derived macrophages(BMDMs)and Tohoku Hospital Pediatrics-1(THP-1)cells.This inhibition was noted alongside the suppression of interferon regulatory factor 3(IRF3)phosphorylation and the expression of interferon-beta(IFN-β),C-X-C motif chemokine ligand 10(CXCL10),and inflammatory mediators such as tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6).The mechanism of action appeared to involve the TGP’s attenuation of the STING-IRF3 interaction,without affecting STING oligomerization,thereby inhibiting the activation of downstream signaling pathways.In vivo,the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid(DMXAA)and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway,offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway.
基金the National Natural Science Foundation of China(82260695,82360781)the Jiangxi Provincial Natural Science Foundation(20232ACB206062)+4 种基金Jiangxi Provincial Department of Education(GJJ2400823)Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-D-202207)Young Jinggang Scholar of Jiangxi Province(Jing Zhang)and New Century Talents Project of Jiangxi Province(2017082,Xiang Li and 2020028,Jing Zhang)the Science and Technology Innovation Team of Jiangxi University of Chinese Medicine(CXTD22001 and CXTD22006)Jiangxi University of Traditional Chinese Medicine Special Zone Construction Project of Traditional Chinese Medicine(New Drug Creation Direction)(TQ-20).
文摘Recently,immunotherapy has redefined cancer treatment by promoting the rapid killing of tumor cells through the immune system.Herbal medicines have been increasingly used as adjunct therapies to complement cancer treatment along with chemotherapy and radiotherapy to delay tumor development,reduce pain,and prolong patient survival.However,the potential immunotherapeutic effects of these herbal derivatives are limited by their structural instability,poor membrane permeability,and low bioavailability.To address this issue,nanotechnology has been used to enhance the activity of active compounds.Therefore,this review focuses on the effectiveness of the active ingredients of herbal medicines in suppressing tumor progression by modulating both the innate and adaptive immune systems,challenges in their delivery,and the application of nanocarriers for the effective delivery of these herbal components.
基金The National Science Foundation of China under contract No.42176040the National(Basic)Research and Development Program of China supported by Ministry of Science and Technology under contract Nos.2016YFA0600902 and 2011CB409802/03+1 种基金the Taishan Scholars Program of Shandong Provincethe Aoshan Talents Program supported by the National Laboratory for Marine Science and Technology(Qingdao).
文摘To understand the temporal and spatial variations in nutrient dynamics,as well as the potential cross-shelf transport of nutrients between the East China Sea(ECS)shelf and the northwestern Pacific Ocean,six field observations covering the ECS were conducted in spring,summer,and autumn in 2011 and 2013.Nutrient dynamics in the ECS and nutrient exchange between shelf water and the open ocean were examined.High concentrations of dissolved inorganic nutrients were detected in the nearshore surface layer and offshore bottom layer in different seasons,and the concentrations of dissolved inorganic nutrients in surface seawater were lower in summer and autumn than in spring.The concentrations of dissolved organic nutrients in Kuroshio surface water were slightly lower in summer than in spring,but the concentrations in Kuroshio subsurface water were slightly higher in summer than in spring.There were abundant nutrient reservoirs in the euphotic zone of the ECS,which explained the high primary productivity.The evaluation of cross-shelf transport indicated that nutrients from shelf water were transported out across the 200 m isobath through the surface layer with the density(σ)less than 23.0 kg/m^(3) in spring.The flux of dissolved inorganic nitrogen transported from the ECS shelf to the Northwest Pacific Ocean in spring was equivalent to 21%of the atmospheric nitrogen deposition in the Northwest Pacific Ocean.In summer,the onshore flux in the surface and bottom layers accounted for 80%of the total flux,and the transportation of nutrients along the surface layer to the continental shelf contributed to the nutrient storage and primary productivity of the euphotic zone in the ECS shelf in summer.
基金financially supported by the National Key Research and Development Program of China(2018YFA0703003)National Natural Science Foundation of China(82072429,52125501,82371590)+6 种基金the Program for Innovation Team of Shaanxi Province(2023-CX-TD-17)the Key Research&Development Program of Shaanxi Province(2024SF-YBXM-355,2020SF-093,2021LLRH-08)the Natural Science Foundation of Henan Province(222300420358)the Postdoctoral Project of Shaanxi Province(2023BSHYDZZ30)the Postdoctoral Fellowship Program of CPSF(GZB20230573)the Institutional Foundation of the First Affiliated Hospital of Xi’an Jiaotong University(2019ZYTS-02)the Fundamental Research Funds for the Central Universities.
文摘The rotator cuff tear has emerged as a significant global health concern.However,existing therapies fail to fully restore the intricate bone-to-tendon gradients,resulting in compromised biomechanical functionalities of the reconstructed enthesis tissues.Herein,a tri-layered core–shell microfibrous scaffold with layer-specific growth factors(GFs)release is developed using coaxial electrohydrodynamic(EHD)printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair.Stromal cell-derived factor-1(SDF-1)is loaded in the shell,while basic fibroblast GF,transforming GF-beta,and bone morphogenetic protein-2 are loaded in the core of the EHD-printed microfibrous scaffolds in a layer-specific manner.Correspondingly,the tri-layered microfibrous scaffolds have a core–shell fiber size of(25.7±5.1)μm,with a pore size sequentially increasing from(81.5±4.6)μm to(173.3±6.9)μm,and to(388.9±6.9μm)for the tenogenic,chondrogenic,and osteogenic instructive layers.A rapid release of embedded GFs is observed within the first 2 d,followed by a faster release of SDF-1 and a slightly slower release of differentiation GFs for approximately four weeks.The coaxial EHD-printed microfibrous scaffolds significantly promote stem cell recruitment and direct their differentiation toward tenocyte,chondrocyte,and osteocyte phenotypes in vitro.When implanted in vivo,the tri-layered core–shell microfibrous scaffolds rapidly restored the biomechanical functions and promoted enthesis tissue regeneration with native-like bone-to-tendon gradients.Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration.
