As cardiovascular disease is the leading cause of global mortality,innovative animal models are vital to demonstrating the translational value of experimental discoveries.Investigations focused on myocardial remodelin...As cardiovascular disease is the leading cause of global mortality,innovative animal models are vital to demonstrating the translational value of experimental discoveries.Investigations focused on myocardial remodeling after ischemia reperfusion(I/R)are well suited to a porcine model,but the evolution of that injury and its impact on electrical conductivity or arrhythmia threshold have been difficult to monitor continuously.Multiple electrode telemetry devices may be fitted to the animals but are costly and prone to damage.Implantable telemetry devices are likewise expensive,carry surgical risk,and are often verified only for single use.Here,we report the utilization of the commercially available Fourth Frontier X2 external telemetry device for continuous monitoring of heart rate and rhythm after myocardial I/R injury in pigs,highlighting sustained monitoring across a 7day study.展开更多
Shikonin,a naphthoquinone compound derived from the root of Lithospermum erythrorhizon,has been extensively studied for its antibacterial,antioxidant,and anti-inflammatory properties.Increasing evidence highlights its...Shikonin,a naphthoquinone compound derived from the root of Lithospermum erythrorhizon,has been extensively studied for its antibacterial,antioxidant,and anti-inflammatory properties.Increasing evidence highlights its potential in treating inflammation-related diseases.However,its clinical application is hindered by challenges such as poor water solubility,rapid metabolism in vivo,and other limitations.Recent advancements have demonstrated that encapsulating shikonin within nanocarriers can significantly enhance its water solubility and pharmacokinetic profile.Building on this,this perspective paper outlines the current landscape of inflammation treatment,explores the anti-inflammatory mechanisms of shikonin,reviews the latest progress in shikonin-based nanomaterials for anti-inflammatory applications,and discusses the challenges and future directions for the clinical translation of shikonin nanoformulations.展开更多
The high polymorphism of histocompatibility complex class Ⅱ(MHC-Ⅱ)alleles and limited immunopeptidomic data hinder pan-species epitope prediction.In this study,leveraging the predictive power of AlphaFold(AF)and the...The high polymorphism of histocompatibility complex class Ⅱ(MHC-Ⅱ)alleles and limited immunopeptidomic data hinder pan-species epitope prediction.In this study,leveraging the predictive power of AlphaFold(AF)and the conserved structural features of the core region of MHC-Ⅱ-binding peptides,derived from a comprehensive analysis of MHC-Ⅱ structure data in the PDB database,we developed a new tool,AF-prediction(AF-pred),with explicit quantitative criteria for MHC-Ⅱ-restricted epitope prediction.We validated AF-pred across human,porcine,bovine,and bat MHC-Ⅱ molecules through large-scale in silico analyses using known immunopeptidome datasets(1000 positive and 1000 negative antigenic peptides),together with in vitro binding assays and crystallographic characterization of newly predicted epitopes.Using uncharacterized bat MHC-Ⅱ structures,we demonstrated that AF-pred’s amino-acid interaction prediction underpins its pan-prediction capability and the underlying rationale of the method.Conversely,this characteristic limits the prediction of atypical MHC-Ⅱ peptide-binding modes.Compared with sequence-based tools,AF-pred demonstrates enhanced cross-species MHC-Ⅱ binding prediction,with higher accuracy and interpretability,and further reveals that iterative AF updates improve AF-pred performance.AF-pred has the potential to facilitate the development of novel T-cell epitope vaccines and advance the“One Health”initiative.展开更多
Objective:To investigate the potential efficacy and safety of Lutai Danshen Baishao granules(LDBG)for treating female melasma associated with kidney deficiency and blood stasis patterns.Methods:A randomized,double-bli...Objective:To investigate the potential efficacy and safety of Lutai Danshen Baishao granules(LDBG)for treating female melasma associated with kidney deficiency and blood stasis patterns.Methods:A randomized,double-blind,placebo-controlled trial was conducted at the Third Central Hospital of Tianjin,China from March to December 2023.A total of 110 female patients with melasma linked to kidney deficiency and blood stasis were enrolled and treated with either LDBG or a placebo twice daily for 60 days.Efficacy was assessed through measures such as the total melasma area,reduced melasma area,reduction rate of melasma area,melasma color score,Melasma Area and Severity Index(MASI)score,and traditional Chinese medicine(TCM)symptom score scale.Safety assessments included routine blood and biochemical tests.Results:Participants in both groups were aged 52-63 years,with no significant differences.After the 2-month intervention,the total melasma area decreased in both groups;however,a greater reduction was observed in the test group[462.50 mm^(2)(12.81%)vs.100.00 mm2(3.11%),P<.001].Moreover,LDBG treatment significantly reduced the MASI and melasma color scores in the test group(P<.05).The total TCM symptom evaluation score significantly decreased(test group:6.00 vs.placebo group:7.00,P=.001),with significant relief in symptoms such as improvement in dark lips,nails,and waist soreness in the test group,compared with that in the placebo group(P<.05).Within-group comparisons revealed that TCM syndrome was significantly alleviated in the test group(P<.05).Conclusion:LDBG intervention shows promising effectiveness in reducing female melasma and alleviating TCM syndromes.展开更多
Colorectal cancer(CRC)is the most prevalent cancer globally,and its traditional treatment modalities commonly encompass radiation therapy,chemotherapy,surgery and the administration of cytotoxic drugs.Currently,novel ...Colorectal cancer(CRC)is the most prevalent cancer globally,and its traditional treatment modalities commonly encompass radiation therapy,chemotherapy,surgery and the administration of cytotoxic drugs.Currently,novel chemotherapy drugs that combine traditional Chinese medicine(TCM)with herbal extracts exhibit superior comprehensive benefits.Herein,we delved into an article authored by Wang et al,focusing specifically on the pharmacological effects of"Herba Patriniae and Coix seed(HC)"and their targeted mechanisms in combating CRC.From the perspective of TCM philosophy,damp-heat stagnation and toxicity are the cardinal pathogenic factors underlying CRC.HC,renowned for their abilities to antipyretic and enhance diuresis,have demonstrated promising efficacy in preliminary studies for the treatment of CRC.These findings offer potential insights in favor of fostering anti-cancer medications.展开更多
The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical ...The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.展开更多
The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose⁃catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monit...The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose⁃catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16℃in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni⁃NTA affinity column.Size⁃exclusion chromatography and SDS⁃PAGE analysis demonstrated that the puri⁃fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD^(+)as a coenzyme to NADP^(+).The optimal temperature and pH of the TeXDH were 40℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26%of the initial enzyme activity,while the divalent metal ions Mg^(2+)or Ca^(2+)could recover the enzyme activity of TeXDH,reaching 103.32%and 110.69%of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn^(2+),Ni^(2+),Cu^(2+),Zn^(2+),Co^(2+),and Cd^(2+)significantly inhibited the activity of TeXDH.ICP⁃MS and molecular doc⁃king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn^(2+)ions and 1 mol/L Mg^(2+)ion.Further⁃more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.展开更多
Alga toxins have recently emerged as an environmental risk factor,especially to neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.However,the associat...Alga toxins have recently emerged as an environmental risk factor,especially to neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.However,the association between the alga toxinsβ-N-methylamino-L-alanine(BMAA),brevetoxin B,cyanoginosin LR,okadaic acid and neurodegenerative diseases remains inadequately investigated.Therefore,the aim of this study was to elucidate the potential associations.Four sets of differentially expressed genes related with BMAA,brevetoxin B,cyanoginosin LR and okadaic acid in Homo sapiens and genes linked to neurodegenerative disease development were respectively collected from the Comparative Toxicogenomic Database.Metascape analysis and cluster community analysis of four alga toxins highlighted protein-protein interaction enrichment and hub genes,while biological processes analysis showed that the dominant pathways involved in harmful effects triggered by four alga toxins were the apoptotic signaling pathway,regulation of amyloid protein formation,inflammatory response and endoplasmic reticulum stress.Genes related to the interactions between four alga toxins and neurodegenerative diseases were selected and analyzed,revealing that the relevant pathways and genes were those involved in apoptotic mitochondrial changes and neuroinflammatory response pathways.The adverse outcome pathway frameworks were constructed according to the analysis results for toxins and associated neurodegenerative diseases.These discoveries provide a new perspective for us to gain a deeper understanding of the neurotoxic effects of four alga toxins.展开更多
Selecting the appropriate algal species is essential to maximize lipid extraction from microalgae.Chlorococcum sp.is a unicellular organism found in both aquatic and terrestrial habitats.Although the influence of nitr...Selecting the appropriate algal species is essential to maximize lipid extraction from microalgae.Chlorococcum sp.is a unicellular organism found in both aquatic and terrestrial habitats.Although the influence of nitrogen on lipid metabolism is well established across various microalgae,its particular effects on Chlorococcum sp.provide novel insights into this relatively underexplored species.Examining how nitrogen affects lipid accumulation in Chlorococcum sp.could reveal new strategies to enhance its application in biodiesel productions.This study aimed to evaluate the lipid content of Chlorococcum novae-angliae and compare the lipid and fatty acid yields between cultures grown in N-supplied and N-starvation culture media.The results show that Chlorococcum sp.cultivated in N-supplied culture medium reached the highest cell count of 2.16±8.18×10^(-8)cells/mL,with a specific growth rate(μ)of 0.55 d^(−1),whereas a cell count of 1.60±6.63×10^(-8)cells/mL was found for the N-starvation culture medium.On the other hand,the highest lipid yield,recorded as 0.098±0.012 g lipid/g wet biomass,mainly consisting of tridecanoic and palmitic acids(77%),was obtained from the N-starvation culture medium.Tridecanoic acid(C13:0)was detected for the first time in C.novae angliae.For the N-supplied culture medium,the lipid yield was 0.082±0.010 g lipid/g wet biomass.Therefore,in cases where maximizing lipid yield is crucial,such as for biofuel production,nitrogen starvation might be a more effective approach,even though it may result in lower overall biomass productivity.However,for applications that prioritize higher biomass,such as animal feed,ensuring sufficient nitrogen levels could be more beneficial.展开更多
Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the bod...Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the body's immune system,leading to the release of a varieties of cytokines and inflammatory mediators,resulting in systemic inflammatory response syndrome[1].展开更多
Herpes simplex virus thymidine kinase(HSVtk)gene therapy is a promising strategy for glioblastoma therapy.However,delivery of plasmid DNA(pDNA)encoding HSVtk into the brain by systemic administration is a challenge si...Herpes simplex virus thymidine kinase(HSVtk)gene therapy is a promising strategy for glioblastoma therapy.However,delivery of plasmid DNA(pDNA)encoding HSVtk into the brain by systemic administration is a challenge since pDNA can hardly penetrate the bloodbrain barrier.In this study,an exosome-membrane(EM)and polymer-based hybrid complex was developed for systemic delivery of pDNA into the brain.Histidine/arginine-linked polyamidoamine(PHR)was used as a carrier.PHR binds to pDNA by electrostatic interaction.The pDNA/PHR complex was mixed with EM and subjected to extrusion to produce pDNA/PHR-EM hybrid complex.For glioblastoma targeting,T7 peptide was attached to the pDNA/PHR-EM complex.Both pDNA/PHR-EM and T7-decorated pDNA/PHR-EM(pDNA/PHREM-T7)had a surface charge of–5 mV and a size of 280 nm.Transfection assays indicated that pDNA/PHR-EM-T7 enhanced the transfection to C6 cells compared with pDNA/PHREM.Intravenous administration of pHSVtk/PHR-EM-T7 showed that pHSVtk/PHR-EM and pHSVtk/PHR-EM-T7 delivered pHSVtk more efficiently than pHSVtk/lipofectamine and pHSVtk/PHR into glioblastoma in vivo.pHSVtk/PHR-EM-T7 had higher delivery efficiency than pHSVtk/PHR-EM.As a result,the HSVtk expression and apoptosis levels in the tumors of the pHSVtk/PHR-EM-T7 group were higher than those of the other control groups.Therefore,the pDNA/PHR-EM-T7 hybrid complex is a useful carrier for systemic delivery of pHSVtk to glioblastoma.展开更多
Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this e...Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this end,in vitro platforms are needed to test therapies directed at salivary(fluid-secreting)cells.However,since these are highly differentiated secretory cells,the maintenance of their differentiated state while expanding in numbers is challenging.In this study,the efficiency of three reversible thermo-ionically crosslinked gels:(1)alginate–gelatin(AG),(2)collagen-containing AG(AGC),and(3)hyaluronic acid-containing AG(AGHA),to recapitulate a native-like environment for human salivary gland(SG)cell expansion and 3D spheroid formation was compared.Although all gels were of mechanical properties comparable to human SG tissue(~11 kPa)and promoted the formation of 3D spheroids,AGHA gels produced larger(>100 cells/spheroid),viable(>93%),proliferative,and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins(aquaporin-5,NKCC1,ZO-1,α-amylase)for 14 days in culture.Moreover,the spheroids responded to agonist-induced stimulation by increasingα-amylase secretory granules.Here,we propose alternative lowcost,reproducible,and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact,highly viable 3D-SG spheroids.展开更多
In this study,injectable bone graft putty samples were developed using fine and coarse melt-quenched 45S5 bioactive glass(BG)incorporated into a carrier system composed of glycerol and polyethylene glycol(PEG)with dif...In this study,injectable bone graft putty samples were developed using fine and coarse melt-quenched 45S5 bioactive glass(BG)incorporated into a carrier system composed of glycerol and polyethylene glycol(PEG)with different average molecular weights.Selected putty samples were further incorporated with varying amounts of Denosumab(5wt%-10wt%)to investigate its influence on rhe-ological behavior and flow properties using mathematical modeling.All PEG/glycerol/45S5-based putty samples exhibited viscoelastic behavior(storage modulus>loss modulus)and pseudoplastic behavior(n<1),with viscosity values required for optimal flow remaining below 1000 Pa∙s.Both viscosity and thixotropic area increased proportionally with higher BG content and smaller-sized BG particles.All putty samples showed more than 98%injectability through a 12G cannula,suggesting potential clinical suitability.However,injectability decreased with smaller cannulas,dropping to 34.7%-58.3%with a 19G cannula and further decreasing with a 23G cannula at higher BG contents.Incorporation of Denosumab preserved viscoelasticity and injectability but modified the flow behavior,shifting it from pseudo-plastic to more Newtonian with higher Denosumab content,while also reducing viscosity and thixotropic area values.Among all tested samples,putty containing a lower amount of Denosumab and smaller-sized BG exhibited the most suitable combination of injectability and rheological features.All putty samples were well described by both the Power law and Herschel-Bulkley rheological models(coeffi-cient of determination>0.95).This study highlights the influence of Denosumab on flowability and rheological relationships and sug-gests potential improvements in bioactivity through a dual synergistic effect of BG and Denosumab in minimally invasive bone graft sys-tems.展开更多
The taxonomic composition and function of endophytic microbial communities in plants are strongly influenced by environmental changes. The impact of nitrogen (N) fertilization on the diversity of microbial communities...The taxonomic composition and function of endophytic microbial communities in plants are strongly influenced by environmental changes. The impact of nitrogen (N) fertilization on the diversity of microbial communities in the underground parts of plants that are tolerant of barren environments throughout their growth period remains largely unexplored. Here, by high-throughput sequencing technology, an experiment was performed at the Pailou Experimental Station of Nanjing Agricultural University, where the soil is a yellow-brown soil, to analyze fluctuations in the microbial communities of Jerusalem artichoke (Helianthus tuberosus L.) underground parts in two treatments, application of N, P, and K fertilizers (NPK) and application of only P and K fertilizers (PK), from March 2018 to January 2019. Total, nitrate, and ammonium N contents of soil and Jerusalem artichoke were significantly decreased in the PK treatment. The bacterial community, particularly Acinetobacter, dominated throughout the growth period, peaking in November and accounting for 88.9% and 87.3%, respectively, in the NPK and PK treatments. The absence of N fertilizer (i.e., NP treatment) had minimal effect on the bacterial community composition compared to the fungal community composition. The α-diversity of bacteria in tubers was not substantial, while that in roots was dramatically reduced in July and September in the NP treatment. Notably, the α-diversity of fungal species exhibited more pronounced seasonal variations than that of bacteria under both fertilizer conditions. The lack of N fertilizer lessened the complexity of bacterial network structure and reduced bacterial community similarity (β-diversity) in different months. Interestingly, the β-diversity and network structure of fungal community in the underground tissues of Jerusalem artichoke showed less sensitivity to N fertilizer compared to those of bacterial community. This study improves the understanding of the dynamic response of endophytic microorganisms to N fertilizer application in the underground parts of Jerusalem artichoke tolerant to barren environments.展开更多
Background Plant tissue culture has emerged as a tool for improving cotton propagation and genetics,but recalcitrance nature of cotton makes it difficult to develop in vitro regeneration.Cotton’s recalcitrance is inf...Background Plant tissue culture has emerged as a tool for improving cotton propagation and genetics,but recalcitrance nature of cotton makes it difficult to develop in vitro regeneration.Cotton’s recalcitrance is influenced by genotype,explant type,and environmental conditions.To overcome these issues,this study uses different machine learning-based predictive models by employing multiple input factors.Cotyledonary node explants of two commercial cotton cultivars(STN-468 and GSN-12)were isolated from 7–8 days old seedlings,preconditioned with 5,10,and 20 mg·L^(-1) kinetin(KIN)for 10 days.Thereafter,explants were postconditioned on full Murashige and Skoog(MS),1/2MS,1/4MS,and full MS+0.05 mg·L^(-1) KIN,cultured in growth room enlightened with red and blue light-emitting diodes(LED)combination.Statistical analysis(analysis of variance,regression analysis)was employed to assess the impact of different treatments on shoot regeneration,with artificial intelligence(AI)models used for confirming the findings.Results GSN-12 exhibited superior shoot regeneration potential compared with STN-468,with an average of 4.99 shoots per explant versus 3.97.Optimal results were achieved with 5 mg·L^(-1) KIN preconditioning,1/4MS postconditioning,and 80%red LED,with maximum of 7.75 shoot count for GSN-12 under these conditions;while STN-468 reached 6.00 shoots under the conditions of 10 mg·L^(-1) KIN preconditioning,MS with 0.05 mg·L^(-1) KIN(postconditioning)and 75.0%red LED.Rooting was successfully achieved with naphthalene acetic acid and activated charcoal.Additionally,three different powerful AI-based models,namely,extreme gradient boost(XGBoost),random forest(RF),and the artificial neural network-based multilayer perceptron(MLP)regression models validated the findings.Conclusion GSN-12 outperformed STN-468 with optimal results from 5 mg·L^(-1) KIN+1/4MS+80%red LED.Application of machine learning-based prediction models to optimize cotton tissue culture protocols for shoot regeneration is helpful to improve cotton regeneration efficiency.展开更多
Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome,with implications for microbial pathogenesis and host defense.Among these,transfer RNA-de...Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome,with implications for microbial pathogenesis and host defense.Among these,transfer RNA-derived small RNAs(tsRNAs)have garnered attention for their roles in modulating microbial behavior.However,the bacterial factors mediating tsRNA interaction and functionality remain poorly understood.In this study,using RNA affinity pull-down assay in combination with mass spectrometry,we identified a putative membrane-bound protein,annotated as P-type ATPase transporter(PtaT)in Fusobacterium nucleatum(Fn),which binds Fn-targeting tsRNAs in a sequence-specific manner.Through targeted mutagenesis and phenotypic characterization,we showed that in both the Fn type strain and a clinical tumor isolate,deletion of ptaT led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition.Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between Fn wild type and PtaT-deficient mutant,highlighting the functional significance of PtaT in purine and pyrimidine metabolism.Furthermore,AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and Fn-targeting tsRNA.By uncovering the first RNA-binding protein in Fn implicated in growth modulation through interactions with host-derived small RNAs(sRNAs),our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.展开更多
Background Eccentric training,such as Nordic hamstring exercise(NHE)training,is commonly used as a preventive measure for hamstring strains.Eccentric training is believed to induce lengthening of muscle fascicles and ...Background Eccentric training,such as Nordic hamstring exercise(NHE)training,is commonly used as a preventive measure for hamstring strains.Eccentric training is believed to induce lengthening of muscle fascicles and to be associated with the addition of sarcomeres in series within muscle fibers.However,the difficulty in measuring sarcomere adaptation in human muscles has severely limited information about the precise mechanisms of adaptation.This study addressed this limitation by measuring the multiscale hamstring muscle adaptations in response to 9 weeks of NHE training and 3 weeks of detraining.Methods Twelve participants completed 9 weeks of supervised NHE training,followed by a 3-week detraining period.We assessed biceps femoris long-head(BFlh)muscle fascicle length,sarcomere length,and serial sarcomere number in the central and distal regions of the muscle.Additionally,we measured muscle volume and eccentric strength at baseline,post-training,and post-detraining.Results NHE training over 9 weeks induced significant architectural and strength adaptations in the BFlh muscle.Fascicle length increased by 19%in the central muscle region and 33%in the distal muscle region.NHE also induced increases in serial sarcomere number(25%in the central region and 49%in the distal region).BFlh muscle volume increased by 8%,and knee flexion strength increased by 40%with training.Following 3 weeks of detraining,fascicle length decreased by 12%in the central region and 16%in the distal region along with reductions in serial sarcomere number.Conclusion Nine weeks of NHE training produced substantial,region-specific increases in BFlh muscle fascicle length,muscle volume,and force generation.The direct measurement of sarcomere lengths revealed that the increased fascicle length was accompanied by the addition of sarcomeres in series within the muscle fascicles.展开更多
The increasing demand for sustainable energy solutions necessitates innovative approaches to biomass utilization.This study introduces a comprehensive biorefinery model that valorizes poplar biomass into high-value pr...The increasing demand for sustainable energy solutions necessitates innovative approaches to biomass utilization.This study introduces a comprehensive biorefinery model that valorizes poplar biomass into high-value products,including ethanol,furfural,phenol,and biochar.These products not only serve as promising sources for biofuel and renewable chemicals but also contribute to pollution mitigation.The approach employs a biphasic pretreatment system utilizing p-toluenesulfonic acid,pentanol,and AlCl_(3) under optimized conditions(120℃ for 45 min),achieving remarkable efficiencies of 95.8%xylan removal,90.2%delignification,and 90.7%glucan recovery.The underlying mechanism,elucidated through density functional theory,demonstrates how the disruption of lignin-carbohydrate complexes via electrostatic and hydrogen-bonding interactions enhances product yields.The cellulose-rich substrate yielded 71.3 g/L ethanol,while solubilized xylan converted to 86.7%furfural without additional acid.Furthermore,lignin pyrolysis produced bio-oil containing over 45.2%phenolic compounds,while biochar demonstrated significant adsorptive capacity for perfluorooctanoic acid.Scaling this biorefinery model to process 140 million tons of poplar biomass annually reduces CO_(2)emissions by 75.3 million tons and provides socioeconomic savings of $17.3 billion,supporting sustainable industrial transformation.展开更多
Controlled intracellular delivery of biomolecular cargo is critical for developing targeted therapeutics and cell reprogramming.Conventional delivery approaches(e.g.,endocytosis of nano-vectors,microinjection,and elec...Controlled intracellular delivery of biomolecular cargo is critical for developing targeted therapeutics and cell reprogramming.Conventional delivery approaches(e.g.,endocytosis of nano-vectors,microinjection,and electroporation)usually require time-consuming uptake processes,labor-intensive operations,and/or costly specialized equipment.Here,we present an acoustofluidics-based intracellular delivery approach capable of effectively delivering various functional nanomaterials to multiple cell types(e.g.,adherent and suspension cancer cells).By tuning the standing acoustic waves in a glass capillary,our approach can push cells in flow to the capillary wall and enhance membrane permeability by increasing membrane stress to deform cells via acoustic radiation forces.Moreover,by coating the capillary with cargo-encapsulated nanoparticles,our approach can achieve controllable cell-nanoparticle contact and facilitate nanomaterial delivery beyond Brownian movement.Based on these mechanisms,we have successfully delivered nanoparticles loaded with small molecules or protein-based cargo to U937 and HeLa cells.Our results demonstrate enhanced delivery efficiency compared to attempts made without the use of acoustofluidics.Moreover,compared to conventional sonoporation methods,our approach does not require special contrast agents with microbubbles.This acoustofluidics-based approach creates exciting opportunities to achieve controllable intracellular delivery of various biomolecular cargoes to diverse cell types for potential therapeutic applications and biophysical studies.展开更多
In this study,we developed a novel bilayered scaffold consisting of a bottom layer composed of the Decellularized Bovine Pericardium(DP)coated with Polyaniline Nanoparticles(PANINPs)and a top layer made of an electros...In this study,we developed a novel bilayered scaffold consisting of a bottom layer composed of the Decellularized Bovine Pericardium(DP)coated with Polyaniline Nanoparticles(PANINPs)and a top layer made of an electrospun Poly(lactic-co-glycolic acid)/Gelatin(PLGA/Gel)membrane incorporated with Vascular Endothelial Growth Fac-tor(VEGF)and hawthorn extract.Functionally,the DP supplies native Extracellular Matrix(ECM)components and mechanical support,while PANINPs provide conductivity.The electrospun PLGA/Gel layer mimics fibrous ECM.It incorporates bioactives,with VEGF promoting pro-angiogenic stimulation and hawthorn extract enhanc-ing anticoagulant activity,as well as increasing surface hydrophilicity.The tissue adhesive ensures the interfacial integrity between the two layers.Decellularization efficiency was confirmed histologically using 4',6-diamidino-2-phenylindole(DAPI)and Hematoxylin-Eosin(H&E)staining.The DP exhibited a DNA content of 115.9±47.8 ng/mg DNA,compared to 982.88±395.42 ng/mg in Native Pericardium(NP).The PANINPs had an average par-ticle size of 104.94±13.7 nm.The conductivity of PANINPs-coated decellularized pericardium was measured to be 9.093±8.6×10-4 S/cm using the four-point probe method.PLGA/Gel membranes containing hawthorn extract(1%,5%,10%,and 15%w/v)and VEGF(0.1μg/mL,0.5μg/mL,and 1μg/mL)were fabricated by electrospinning,result-ing in fiber diameters between 850 and 1200 nm and pore sizes between 14 and 20μm.The anticoagulant efficiency of the membranes containing hawthorn extract reached 430 s in the Activated Partial Thromboplastin Time Assay(aPTT).Mechanical testing revealed a tensile strength of 22.70±6.33 MPa,an elongation of 53.58±10.63%,and Young's modulus of 0.67±0.10 MPa.The scaffold also exhibited over 91%cell viability and excellent cardiomyo-cyte adhesion.The hemolysis ratio was determined to be 0.421±0.191%,which confirms its blood compatibility.Our results indicate that the proposed bilayered scaffold can be a promising candidate for cardiac patch applications.展开更多
基金College of Graduate Studies,Medical University of South Carolina,Grant/Award Number:SCTR 2305National Heart,Lung,and Blood Institute,Grant/Award Number:1U01HL169361-01NIH:NCATS,Grant/Award Number:UL1TR001450。
文摘As cardiovascular disease is the leading cause of global mortality,innovative animal models are vital to demonstrating the translational value of experimental discoveries.Investigations focused on myocardial remodeling after ischemia reperfusion(I/R)are well suited to a porcine model,but the evolution of that injury and its impact on electrical conductivity or arrhythmia threshold have been difficult to monitor continuously.Multiple electrode telemetry devices may be fitted to the animals but are costly and prone to damage.Implantable telemetry devices are likewise expensive,carry surgical risk,and are often verified only for single use.Here,we report the utilization of the commercially available Fourth Frontier X2 external telemetry device for continuous monitoring of heart rate and rhythm after myocardial I/R injury in pigs,highlighting sustained monitoring across a 7day study.
基金supported by the National Natural Science Foundation of China(82373393),Xinjiang Uygur Autonomous Region“Tianchi Yingcai”Project(2023TCYCQNBS02)Xinjiang Uygur Autonomous Region Colleges and Universities Basic Research Operating Expenses Scientific Research Project(XJEDU2022P106).
文摘Shikonin,a naphthoquinone compound derived from the root of Lithospermum erythrorhizon,has been extensively studied for its antibacterial,antioxidant,and anti-inflammatory properties.Increasing evidence highlights its potential in treating inflammation-related diseases.However,its clinical application is hindered by challenges such as poor water solubility,rapid metabolism in vivo,and other limitations.Recent advancements have demonstrated that encapsulating shikonin within nanocarriers can significantly enhance its water solubility and pharmacokinetic profile.Building on this,this perspective paper outlines the current landscape of inflammation treatment,explores the anti-inflammatory mechanisms of shikonin,reviews the latest progress in shikonin-based nanomaterials for anti-inflammatory applications,and discusses the challenges and future directions for the clinical translation of shikonin nanoformulations.
基金supported by the National Key Research and Development Program of China(grant number 2021YFD1800100 to N.Z.)the National Natural Science Foundation of China(grant number 32172871 to N.Z.)the 2115 Talent Development Program of China Agricultural University to N.Z.This study was supported by High-performance Computing Platform of China Agricultural University.
文摘The high polymorphism of histocompatibility complex class Ⅱ(MHC-Ⅱ)alleles and limited immunopeptidomic data hinder pan-species epitope prediction.In this study,leveraging the predictive power of AlphaFold(AF)and the conserved structural features of the core region of MHC-Ⅱ-binding peptides,derived from a comprehensive analysis of MHC-Ⅱ structure data in the PDB database,we developed a new tool,AF-prediction(AF-pred),with explicit quantitative criteria for MHC-Ⅱ-restricted epitope prediction.We validated AF-pred across human,porcine,bovine,and bat MHC-Ⅱ molecules through large-scale in silico analyses using known immunopeptidome datasets(1000 positive and 1000 negative antigenic peptides),together with in vitro binding assays and crystallographic characterization of newly predicted epitopes.Using uncharacterized bat MHC-Ⅱ structures,we demonstrated that AF-pred’s amino-acid interaction prediction underpins its pan-prediction capability and the underlying rationale of the method.Conversely,this characteristic limits the prediction of atypical MHC-Ⅱ peptide-binding modes.Compared with sequence-based tools,AF-pred demonstrates enhanced cross-species MHC-Ⅱ binding prediction,with higher accuracy and interpretability,and further reveals that iterative AF updates improve AF-pred performance.AF-pred has the potential to facilitate the development of novel T-cell epitope vaccines and advance the“One Health”initiative.
基金funded by the National Key Research and Development Plan of the Traditional Chinese Medicine Modernization Research Key Project(2018YFC1706800).
文摘Objective:To investigate the potential efficacy and safety of Lutai Danshen Baishao granules(LDBG)for treating female melasma associated with kidney deficiency and blood stasis patterns.Methods:A randomized,double-blind,placebo-controlled trial was conducted at the Third Central Hospital of Tianjin,China from March to December 2023.A total of 110 female patients with melasma linked to kidney deficiency and blood stasis were enrolled and treated with either LDBG or a placebo twice daily for 60 days.Efficacy was assessed through measures such as the total melasma area,reduced melasma area,reduction rate of melasma area,melasma color score,Melasma Area and Severity Index(MASI)score,and traditional Chinese medicine(TCM)symptom score scale.Safety assessments included routine blood and biochemical tests.Results:Participants in both groups were aged 52-63 years,with no significant differences.After the 2-month intervention,the total melasma area decreased in both groups;however,a greater reduction was observed in the test group[462.50 mm^(2)(12.81%)vs.100.00 mm2(3.11%),P<.001].Moreover,LDBG treatment significantly reduced the MASI and melasma color scores in the test group(P<.05).The total TCM symptom evaluation score significantly decreased(test group:6.00 vs.placebo group:7.00,P=.001),with significant relief in symptoms such as improvement in dark lips,nails,and waist soreness in the test group,compared with that in the placebo group(P<.05).Within-group comparisons revealed that TCM syndrome was significantly alleviated in the test group(P<.05).Conclusion:LDBG intervention shows promising effectiveness in reducing female melasma and alleviating TCM syndromes.
基金National Natural Science Foundation of China,No.81970529The Natural Science Foundation of Jilin Province,No.20230508074RC and No.YDZJ202401218ZYTS.
文摘Colorectal cancer(CRC)is the most prevalent cancer globally,and its traditional treatment modalities commonly encompass radiation therapy,chemotherapy,surgery and the administration of cytotoxic drugs.Currently,novel chemotherapy drugs that combine traditional Chinese medicine(TCM)with herbal extracts exhibit superior comprehensive benefits.Herein,we delved into an article authored by Wang et al,focusing specifically on the pharmacological effects of"Herba Patriniae and Coix seed(HC)"and their targeted mechanisms in combating CRC.From the perspective of TCM philosophy,damp-heat stagnation and toxicity are the cardinal pathogenic factors underlying CRC.HC,renowned for their abilities to antipyretic and enhance diuresis,have demonstrated promising efficacy in preliminary studies for the treatment of CRC.These findings offer potential insights in favor of fostering anti-cancer medications.
基金support of the National Natural Science Foundation of China(Grant No.52205593)Shaanxi Natural Science Foundation Project(2024JC-YBMS-711).
文摘The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.
基金湖南省教育厅基金优秀青年项目(No.22B0482)湖南科技大学博士启动基金(No.E51992 and E51993)资助。
文摘The xylitol dehydrogenase(XDH)is a crucial enzyme involved in the xylose utilization in pentose⁃catabolizing yeasts and fungi.In addition to producing xylulose,XDH can also be employed to develop a biosensor for monitoring xylitol concentration.In this study,the gene encoding the thermophilic fungus Talaromyces emersonii XDH(TeXDH)was heterologously expressed in Escherichia coli BL21(DE3)at 16℃in the soluble form.Recombinant TeXDH with high purity was purified by using a Ni⁃NTA affinity column.Size⁃exclusion chromatography and SDS⁃PAGE analysis demonstrated that the puri⁃fied recombinant TeXDH exists as a native trimer with a molecular mass of approximately 116 kD,and is composed of three identical subunits,each with a molecular weight of around 39 kD.The TeXDH strictly preferred NAD^(+)as a coenzyme to NADP^(+).The optimal temperature and pH of the TeXDH were 40℃and 10.0,respectively.After EDTA treatment,the enzyme activity of TeXDH decreased to 43.26%of the initial enzyme activity,while the divalent metal ions Mg^(2+)or Ca^(2+)could recover the enzyme activity of TeXDH,reaching 103.32%and 110.69%of the initial enzyme activity,respectively,making them the optimal divalent metal ion cofactors for TeXDH enzyme.However,the divalent metal ions of Mn^(2+),Ni^(2+),Cu^(2+),Zn^(2+),Co^(2+),and Cd^(2+)significantly inhibited the activity of TeXDH.ICP⁃MS and molecular doc⁃king studies revealed that 1 mol/L of TeXDH bound 2 mol/L Zn^(2+)ions and 1 mol/L Mg^(2+)ion.Further⁃more,TeXDH exhibited a high specificity for xylitol,laying the foundation for the development of future xylitol biosensors.
基金supported by the Natural Science Foundation of Shandong province(Nos.ZR2019MH048 and ZR2022QC149)the Double First-class Disciplines Construction Fund Project from Harbin Institute of Technology at Weihai(No.2023SYLHY18)Weihai Science and Technology Development Program。
文摘Alga toxins have recently emerged as an environmental risk factor,especially to neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease and amyotrophic lateral sclerosis.However,the association between the alga toxinsβ-N-methylamino-L-alanine(BMAA),brevetoxin B,cyanoginosin LR,okadaic acid and neurodegenerative diseases remains inadequately investigated.Therefore,the aim of this study was to elucidate the potential associations.Four sets of differentially expressed genes related with BMAA,brevetoxin B,cyanoginosin LR and okadaic acid in Homo sapiens and genes linked to neurodegenerative disease development were respectively collected from the Comparative Toxicogenomic Database.Metascape analysis and cluster community analysis of four alga toxins highlighted protein-protein interaction enrichment and hub genes,while biological processes analysis showed that the dominant pathways involved in harmful effects triggered by four alga toxins were the apoptotic signaling pathway,regulation of amyloid protein formation,inflammatory response and endoplasmic reticulum stress.Genes related to the interactions between four alga toxins and neurodegenerative diseases were selected and analyzed,revealing that the relevant pathways and genes were those involved in apoptotic mitochondrial changes and neuroinflammatory response pathways.The adverse outcome pathway frameworks were constructed according to the analysis results for toxins and associated neurodegenerative diseases.These discoveries provide a new perspective for us to gain a deeper understanding of the neurotoxic effects of four alga toxins.
基金financially supported by Ege University Scientific Research Projects(BAP)with project number 30846Ege University Scientific Research Projects(BAP)for the financial support.
文摘Selecting the appropriate algal species is essential to maximize lipid extraction from microalgae.Chlorococcum sp.is a unicellular organism found in both aquatic and terrestrial habitats.Although the influence of nitrogen on lipid metabolism is well established across various microalgae,its particular effects on Chlorococcum sp.provide novel insights into this relatively underexplored species.Examining how nitrogen affects lipid accumulation in Chlorococcum sp.could reveal new strategies to enhance its application in biodiesel productions.This study aimed to evaluate the lipid content of Chlorococcum novae-angliae and compare the lipid and fatty acid yields between cultures grown in N-supplied and N-starvation culture media.The results show that Chlorococcum sp.cultivated in N-supplied culture medium reached the highest cell count of 2.16±8.18×10^(-8)cells/mL,with a specific growth rate(μ)of 0.55 d^(−1),whereas a cell count of 1.60±6.63×10^(-8)cells/mL was found for the N-starvation culture medium.On the other hand,the highest lipid yield,recorded as 0.098±0.012 g lipid/g wet biomass,mainly consisting of tridecanoic and palmitic acids(77%),was obtained from the N-starvation culture medium.Tridecanoic acid(C13:0)was detected for the first time in C.novae angliae.For the N-supplied culture medium,the lipid yield was 0.082±0.010 g lipid/g wet biomass.Therefore,in cases where maximizing lipid yield is crucial,such as for biofuel production,nitrogen starvation might be a more effective approach,even though it may result in lower overall biomass productivity.However,for applications that prioritize higher biomass,such as animal feed,ensuring sufficient nitrogen levels could be more beneficial.
基金supported by the Sichuan Science and Technology Program(2022NSFSC1936)Doctoral Scientific Research Start-up Foundation of China West Normal University(412984).
文摘Introduction When the body is infected,pathogenic microorganisms and their toxins can enter the blood circulation and grow and proliferate in the blood,producing more toxins.These toxins and pathogens activate the body's immune system,leading to the release of a varieties of cytokines and inflammatory mediators,resulting in systemic inflammatory response syndrome[1].
基金supported by the Individual Basic Science&Engineering Research Program(NRF-2022R1A2B5B01001920)through the National Research Foundation,funded by the Ministry of Science and ICT in Korea.
文摘Herpes simplex virus thymidine kinase(HSVtk)gene therapy is a promising strategy for glioblastoma therapy.However,delivery of plasmid DNA(pDNA)encoding HSVtk into the brain by systemic administration is a challenge since pDNA can hardly penetrate the bloodbrain barrier.In this study,an exosome-membrane(EM)and polymer-based hybrid complex was developed for systemic delivery of pDNA into the brain.Histidine/arginine-linked polyamidoamine(PHR)was used as a carrier.PHR binds to pDNA by electrostatic interaction.The pDNA/PHR complex was mixed with EM and subjected to extrusion to produce pDNA/PHR-EM hybrid complex.For glioblastoma targeting,T7 peptide was attached to the pDNA/PHR-EM complex.Both pDNA/PHR-EM and T7-decorated pDNA/PHR-EM(pDNA/PHREM-T7)had a surface charge of–5 mV and a size of 280 nm.Transfection assays indicated that pDNA/PHR-EM-T7 enhanced the transfection to C6 cells compared with pDNA/PHREM.Intravenous administration of pHSVtk/PHR-EM-T7 showed that pHSVtk/PHR-EM and pHSVtk/PHR-EM-T7 delivered pHSVtk more efficiently than pHSVtk/lipofectamine and pHSVtk/PHR into glioblastoma in vivo.pHSVtk/PHR-EM-T7 had higher delivery efficiency than pHSVtk/PHR-EM.As a result,the HSVtk expression and apoptosis levels in the tumors of the pHSVtk/PHR-EM-T7 group were higher than those of the other control groups.Therefore,the pDNA/PHR-EM-T7 hybrid complex is a useful carrier for systemic delivery of pHSVtk to glioblastoma.
基金support from Fonds de Recherche du Québec Santé(FRQS,grant no.281271)support from FRQS doctoral award #304367funding from CFI,Rheolution Inc.,and Investissement Québec.
文摘Xerostomia(dry mouth)is frequently experienced by patients treated with radiotherapy for head and neck cancers or with Sjögren’s syndrome,with no permanent cure existing for this debilitating condition.To this end,in vitro platforms are needed to test therapies directed at salivary(fluid-secreting)cells.However,since these are highly differentiated secretory cells,the maintenance of their differentiated state while expanding in numbers is challenging.In this study,the efficiency of three reversible thermo-ionically crosslinked gels:(1)alginate–gelatin(AG),(2)collagen-containing AG(AGC),and(3)hyaluronic acid-containing AG(AGHA),to recapitulate a native-like environment for human salivary gland(SG)cell expansion and 3D spheroid formation was compared.Although all gels were of mechanical properties comparable to human SG tissue(~11 kPa)and promoted the formation of 3D spheroids,AGHA gels produced larger(>100 cells/spheroid),viable(>93%),proliferative,and well-organized 3D SG spheroids while spatially and temporally maintaining the high expression of key SG proteins(aquaporin-5,NKCC1,ZO-1,α-amylase)for 14 days in culture.Moreover,the spheroids responded to agonist-induced stimulation by increasingα-amylase secretory granules.Here,we propose alternative lowcost,reproducible,and reversible AG-based 3D hydrogels that allow the facile and rapid retrieval of intact,highly viable 3D-SG spheroids.
基金supported by Yildiz Technical University Scientific Research Projects Coordination Unit under project number FBA-2023-5377support from the Scientific and Technological Research Council of Turkey(TUBITAK)under the BIDEB/2211-A National PhD Scholarship Program and 2250-Performance-Based Scholarships Program for PhD.
文摘In this study,injectable bone graft putty samples were developed using fine and coarse melt-quenched 45S5 bioactive glass(BG)incorporated into a carrier system composed of glycerol and polyethylene glycol(PEG)with different average molecular weights.Selected putty samples were further incorporated with varying amounts of Denosumab(5wt%-10wt%)to investigate its influence on rhe-ological behavior and flow properties using mathematical modeling.All PEG/glycerol/45S5-based putty samples exhibited viscoelastic behavior(storage modulus>loss modulus)and pseudoplastic behavior(n<1),with viscosity values required for optimal flow remaining below 1000 Pa∙s.Both viscosity and thixotropic area increased proportionally with higher BG content and smaller-sized BG particles.All putty samples showed more than 98%injectability through a 12G cannula,suggesting potential clinical suitability.However,injectability decreased with smaller cannulas,dropping to 34.7%-58.3%with a 19G cannula and further decreasing with a 23G cannula at higher BG contents.Incorporation of Denosumab preserved viscoelasticity and injectability but modified the flow behavior,shifting it from pseudo-plastic to more Newtonian with higher Denosumab content,while also reducing viscosity and thixotropic area values.Among all tested samples,putty containing a lower amount of Denosumab and smaller-sized BG exhibited the most suitable combination of injectability and rheological features.All putty samples were well described by both the Power law and Herschel-Bulkley rheological models(coeffi-cient of determination>0.95).This study highlights the influence of Denosumab on flowability and rheological relationships and sug-gests potential improvements in bioactivity through a dual synergistic effect of BG and Denosumab in minimally invasive bone graft sys-tems.
基金supported by the Foreign Experts Project of China(No.G2022145002 L)the National Natural Science Foundation of China(No.31571702)the Priority Academic Program Development of Jiangsu Higher Education Institutions,China(No.809001).
文摘The taxonomic composition and function of endophytic microbial communities in plants are strongly influenced by environmental changes. The impact of nitrogen (N) fertilization on the diversity of microbial communities in the underground parts of plants that are tolerant of barren environments throughout their growth period remains largely unexplored. Here, by high-throughput sequencing technology, an experiment was performed at the Pailou Experimental Station of Nanjing Agricultural University, where the soil is a yellow-brown soil, to analyze fluctuations in the microbial communities of Jerusalem artichoke (Helianthus tuberosus L.) underground parts in two treatments, application of N, P, and K fertilizers (NPK) and application of only P and K fertilizers (PK), from March 2018 to January 2019. Total, nitrate, and ammonium N contents of soil and Jerusalem artichoke were significantly decreased in the PK treatment. The bacterial community, particularly Acinetobacter, dominated throughout the growth period, peaking in November and accounting for 88.9% and 87.3%, respectively, in the NPK and PK treatments. The absence of N fertilizer (i.e., NP treatment) had minimal effect on the bacterial community composition compared to the fungal community composition. The α-diversity of bacteria in tubers was not substantial, while that in roots was dramatically reduced in July and September in the NP treatment. Notably, the α-diversity of fungal species exhibited more pronounced seasonal variations than that of bacteria under both fertilizer conditions. The lack of N fertilizer lessened the complexity of bacterial network structure and reduced bacterial community similarity (β-diversity) in different months. Interestingly, the β-diversity and network structure of fungal community in the underground tissues of Jerusalem artichoke showed less sensitivity to N fertilizer compared to those of bacterial community. This study improves the understanding of the dynamic response of endophytic microorganisms to N fertilizer application in the underground parts of Jerusalem artichoke tolerant to barren environments.
文摘Background Plant tissue culture has emerged as a tool for improving cotton propagation and genetics,but recalcitrance nature of cotton makes it difficult to develop in vitro regeneration.Cotton’s recalcitrance is influenced by genotype,explant type,and environmental conditions.To overcome these issues,this study uses different machine learning-based predictive models by employing multiple input factors.Cotyledonary node explants of two commercial cotton cultivars(STN-468 and GSN-12)were isolated from 7–8 days old seedlings,preconditioned with 5,10,and 20 mg·L^(-1) kinetin(KIN)for 10 days.Thereafter,explants were postconditioned on full Murashige and Skoog(MS),1/2MS,1/4MS,and full MS+0.05 mg·L^(-1) KIN,cultured in growth room enlightened with red and blue light-emitting diodes(LED)combination.Statistical analysis(analysis of variance,regression analysis)was employed to assess the impact of different treatments on shoot regeneration,with artificial intelligence(AI)models used for confirming the findings.Results GSN-12 exhibited superior shoot regeneration potential compared with STN-468,with an average of 4.99 shoots per explant versus 3.97.Optimal results were achieved with 5 mg·L^(-1) KIN preconditioning,1/4MS postconditioning,and 80%red LED,with maximum of 7.75 shoot count for GSN-12 under these conditions;while STN-468 reached 6.00 shoots under the conditions of 10 mg·L^(-1) KIN preconditioning,MS with 0.05 mg·L^(-1) KIN(postconditioning)and 75.0%red LED.Rooting was successfully achieved with naphthalene acetic acid and activated charcoal.Additionally,three different powerful AI-based models,namely,extreme gradient boost(XGBoost),random forest(RF),and the artificial neural network-based multilayer perceptron(MLP)regression models validated the findings.Conclusion GSN-12 outperformed STN-468 with optimal results from 5 mg·L^(-1) KIN+1/4MS+80%red LED.Application of machine learning-based prediction models to optimize cotton tissue culture protocols for shoot regeneration is helpful to improve cotton regeneration efficiency.
基金supported by NSF 2333230 (J.L.),NIH National Institute of Dental and Craniofacial Research (NIDCR) awards,DE030943 (X.H.),DE023810 (X.H.) and DE031329 (J.L.),T90 DE026110,and K99 DE033794 (to P.-T.D.)
文摘Host-derived small RNAs are emerging as critical regulators in the dynamic interactions between host tissues and the microbiome,with implications for microbial pathogenesis and host defense.Among these,transfer RNA-derived small RNAs(tsRNAs)have garnered attention for their roles in modulating microbial behavior.However,the bacterial factors mediating tsRNA interaction and functionality remain poorly understood.In this study,using RNA affinity pull-down assay in combination with mass spectrometry,we identified a putative membrane-bound protein,annotated as P-type ATPase transporter(PtaT)in Fusobacterium nucleatum(Fn),which binds Fn-targeting tsRNAs in a sequence-specific manner.Through targeted mutagenesis and phenotypic characterization,we showed that in both the Fn type strain and a clinical tumor isolate,deletion of ptaT led to reduced tsRNA intake and enhanced resistance to tsRNA-induced growth inhibition.Global RNA sequencing and label-free Raman spectroscopy revealed the phenotypic differences between Fn wild type and PtaT-deficient mutant,highlighting the functional significance of PtaT in purine and pyrimidine metabolism.Furthermore,AlphaFold 3 prediction provides evidence supporting the specific binding between PtaT and Fn-targeting tsRNA.By uncovering the first RNA-binding protein in Fn implicated in growth modulation through interactions with host-derived small RNAs(sRNAs),our study offers new insights into sRNA-mediated host-pathogen interplay within the context of microbiome-host interactions.
基金supported by the Australian Research Council Discovery Project(DP200101476)in part by National Institute of Health grants(R01 AR077604,RO1 EB002524,RO1 AR079431,and P41 EB02706)+1 种基金Stanford Graduate Fellowship,The University of Queensland Graduate Scholarship,National Health and Medical Research Council of Australia Fellowship(#1194937)by Wu Tsai Human Performance Alliance at Stanford University and the Joe and Clara Tsai Foundation。
文摘Background Eccentric training,such as Nordic hamstring exercise(NHE)training,is commonly used as a preventive measure for hamstring strains.Eccentric training is believed to induce lengthening of muscle fascicles and to be associated with the addition of sarcomeres in series within muscle fibers.However,the difficulty in measuring sarcomere adaptation in human muscles has severely limited information about the precise mechanisms of adaptation.This study addressed this limitation by measuring the multiscale hamstring muscle adaptations in response to 9 weeks of NHE training and 3 weeks of detraining.Methods Twelve participants completed 9 weeks of supervised NHE training,followed by a 3-week detraining period.We assessed biceps femoris long-head(BFlh)muscle fascicle length,sarcomere length,and serial sarcomere number in the central and distal regions of the muscle.Additionally,we measured muscle volume and eccentric strength at baseline,post-training,and post-detraining.Results NHE training over 9 weeks induced significant architectural and strength adaptations in the BFlh muscle.Fascicle length increased by 19%in the central muscle region and 33%in the distal muscle region.NHE also induced increases in serial sarcomere number(25%in the central region and 49%in the distal region).BFlh muscle volume increased by 8%,and knee flexion strength increased by 40%with training.Following 3 weeks of detraining,fascicle length decreased by 12%in the central region and 16%in the distal region along with reductions in serial sarcomere number.Conclusion Nine weeks of NHE training produced substantial,region-specific increases in BFlh muscle fascicle length,muscle volume,and force generation.The direct measurement of sarcomere lengths revealed that the increased fascicle length was accompanied by the addition of sarcomeres in series within the muscle fascicles.
基金funded by the National Natural Science Foundation of China(22278189,22478154)the Fundamental Research Funds for the Central Universities(Jiangnan University,JUSRP202501024)the Priority Academic Program Development of Jiangsu Higher Education Institutions,the 111 Project(No.111-2-06)。
文摘The increasing demand for sustainable energy solutions necessitates innovative approaches to biomass utilization.This study introduces a comprehensive biorefinery model that valorizes poplar biomass into high-value products,including ethanol,furfural,phenol,and biochar.These products not only serve as promising sources for biofuel and renewable chemicals but also contribute to pollution mitigation.The approach employs a biphasic pretreatment system utilizing p-toluenesulfonic acid,pentanol,and AlCl_(3) under optimized conditions(120℃ for 45 min),achieving remarkable efficiencies of 95.8%xylan removal,90.2%delignification,and 90.7%glucan recovery.The underlying mechanism,elucidated through density functional theory,demonstrates how the disruption of lignin-carbohydrate complexes via electrostatic and hydrogen-bonding interactions enhances product yields.The cellulose-rich substrate yielded 71.3 g/L ethanol,while solubilized xylan converted to 86.7%furfural without additional acid.Furthermore,lignin pyrolysis produced bio-oil containing over 45.2%phenolic compounds,while biochar demonstrated significant adsorptive capacity for perfluorooctanoic acid.Scaling this biorefinery model to process 140 million tons of poplar biomass annually reduces CO_(2)emissions by 75.3 million tons and provides socioeconomic savings of $17.3 billion,supporting sustainable industrial transformation.
基金the support from the National Institutes of Health(R01GM141055)the National Science Foundation(CMMI2104295)+7 种基金the China Scholarship Councilthe NIH/NCATS UCLA CTSI(UL1TR001881)through the UC Center for Accelerated Innovationsupported by the National Science Foundation Graduate Research Fellowship(1644868)support from the UCLA Innovation Fund MedTech Innovator Awardthe Challenge Initiative at UCLAseed funding provided through a UCLA David Geffen School of Medicine Regenerative Medicine Theme Awardthe support provided by the NIH Common Fund through an NIH Director's Early Independence Award co-funded by the National Institute of Dental and Craniofacial Research and Office of the Director,NIH under award number(DP50D028181)the NIH for a predoctoral fellowship supported by the National Heart,Lung,and Blood Institute of the National Institutes of Health under Award Number(F31HL149356)。
文摘Controlled intracellular delivery of biomolecular cargo is critical for developing targeted therapeutics and cell reprogramming.Conventional delivery approaches(e.g.,endocytosis of nano-vectors,microinjection,and electroporation)usually require time-consuming uptake processes,labor-intensive operations,and/or costly specialized equipment.Here,we present an acoustofluidics-based intracellular delivery approach capable of effectively delivering various functional nanomaterials to multiple cell types(e.g.,adherent and suspension cancer cells).By tuning the standing acoustic waves in a glass capillary,our approach can push cells in flow to the capillary wall and enhance membrane permeability by increasing membrane stress to deform cells via acoustic radiation forces.Moreover,by coating the capillary with cargo-encapsulated nanoparticles,our approach can achieve controllable cell-nanoparticle contact and facilitate nanomaterial delivery beyond Brownian movement.Based on these mechanisms,we have successfully delivered nanoparticles loaded with small molecules or protein-based cargo to U937 and HeLa cells.Our results demonstrate enhanced delivery efficiency compared to attempts made without the use of acoustofluidics.Moreover,compared to conventional sonoporation methods,our approach does not require special contrast agents with microbubbles.This acoustofluidics-based approach creates exciting opportunities to achieve controllable intracellular delivery of various biomolecular cargoes to diverse cell types for potential therapeutic applications and biophysical studies.
文摘In this study,we developed a novel bilayered scaffold consisting of a bottom layer composed of the Decellularized Bovine Pericardium(DP)coated with Polyaniline Nanoparticles(PANINPs)and a top layer made of an electrospun Poly(lactic-co-glycolic acid)/Gelatin(PLGA/Gel)membrane incorporated with Vascular Endothelial Growth Fac-tor(VEGF)and hawthorn extract.Functionally,the DP supplies native Extracellular Matrix(ECM)components and mechanical support,while PANINPs provide conductivity.The electrospun PLGA/Gel layer mimics fibrous ECM.It incorporates bioactives,with VEGF promoting pro-angiogenic stimulation and hawthorn extract enhanc-ing anticoagulant activity,as well as increasing surface hydrophilicity.The tissue adhesive ensures the interfacial integrity between the two layers.Decellularization efficiency was confirmed histologically using 4',6-diamidino-2-phenylindole(DAPI)and Hematoxylin-Eosin(H&E)staining.The DP exhibited a DNA content of 115.9±47.8 ng/mg DNA,compared to 982.88±395.42 ng/mg in Native Pericardium(NP).The PANINPs had an average par-ticle size of 104.94±13.7 nm.The conductivity of PANINPs-coated decellularized pericardium was measured to be 9.093±8.6×10-4 S/cm using the four-point probe method.PLGA/Gel membranes containing hawthorn extract(1%,5%,10%,and 15%w/v)and VEGF(0.1μg/mL,0.5μg/mL,and 1μg/mL)were fabricated by electrospinning,result-ing in fiber diameters between 850 and 1200 nm and pore sizes between 14 and 20μm.The anticoagulant efficiency of the membranes containing hawthorn extract reached 430 s in the Activated Partial Thromboplastin Time Assay(aPTT).Mechanical testing revealed a tensile strength of 22.70±6.33 MPa,an elongation of 53.58±10.63%,and Young's modulus of 0.67±0.10 MPa.The scaffold also exhibited over 91%cell viability and excellent cardiomyo-cyte adhesion.The hemolysis ratio was determined to be 0.421±0.191%,which confirms its blood compatibility.Our results indicate that the proposed bilayered scaffold can be a promising candidate for cardiac patch applications.
