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
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
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
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
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
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
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
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
Foods are often contaminated by multiple foodborne pathogens,which threatens human health.In this work,we developed a microfluidic biosensor for multiplex immunoassay of foodborne bacteria with agitation driven by pro...Foods are often contaminated by multiple foodborne pathogens,which threatens human health.In this work,we developed a microfluidic biosensor for multiplex immunoassay of foodborne bacteria with agitation driven by programmed audio signals.This agitation,powered by the vibration of a speaker cone during music playing,accelerated the mass transport in the incubation process to form bacterial complexes within 10 min.Immunoassay reagents of the two target bacteria(Escherichia coli O157:H7 and Salmonella typhimurium)were preloaded into the corresponding fore-vacuum storage chamber on the chip,and released to participate in the subsequent immune analysis process by piercing the chambers.All the detection processes were integrated into a single microfluidic chip and controlled by a smartphone through Bluetooth.Under selected conditions,wide linear ranges and low limits of detection(LODs<2CFU/m L)were obtained,and real food samples were successfully determined within 30 min.This biosensing method can be extended to wide-ranging applications by loading different recognizing reagents.展开更多
This observational cohort study investigated the potential of a novel sperm-washing medium(SWM)enriched with serotonin(5-HT),L-carnitine(L-C),and coenzyme Q10(CoQ10)to enhance sperm motility and reduce DNA damage.It c...This observational cohort study investigated the potential of a novel sperm-washing medium(SWM)enriched with serotonin(5-HT),L-carnitine(L-C),and coenzyme Q10(CoQ10)to enhance sperm motility and reduce DNA damage.It compared this innovative medium(5-HT/L-C/CoQ10 SWM)with two widely used commercial media(SWM 1 and SWM 2).Ninety-eight volunteers from an infertility clinic provided semen samples,which were divided into three aliquots for analysis in different SWMs:group 1,SWM was composed of hydroxyethyl piperazineethanesulfonic acid(HEPES),sodium bicarbonate,human serum albumin(HSA),taurine,and gentamicin sulfate(SWM 1);group 2,SWM was composed of HEPES,sodium bicarbonate,and HSA(SWM 2);and group 3,SWM was composed of HEPES-buffered human tubal fluid supplemented with 5-HT,L-C,and CoQ10(5-HT/L-C/CoQ10 SWM).Sperm motility was categorized as progressive,nonprogressive,or immotile.Apoptosis,reactive oxygen species(ROS)production,and DNA fragmentation were also assessed.There were no significant differences in total or progressive sperm motility among the groups.Spermatozoa in group 3 exhibited reduced apoptosis,necrosis,and ROS levels and increased viability.No significant differences were observed in the DNA fragmentation index among groups.The 5-HT/L-C/CoQ10 SWM reduced sperm oxidative stress and apoptosis compared with those of the two commercially available SWMs,suggesting that 5-HT/L-C/CoQ10 SWM could be useful for enhancing in vitro fertilization success rates.展开更多
In this editorial,we comment on the article by Mei et al.Nonalcoholic steatohep-atitis(NASH)is a severe inflammatory subtype of nonalcoholic fatty liver disease(NAFLD)with pathological features including steatosis,hep...In this editorial,we comment on the article by Mei et al.Nonalcoholic steatohep-atitis(NASH)is a severe inflammatory subtype of nonalcoholic fatty liver disease(NAFLD)with pathological features including steatosis,hepatocellular damage,and varying degrees of fibrosis.With the epidemic of metabolic diseases and obesity,the prevalence of NAFLD in China has increased,and it is now similar to that in developed countries;thus,NAFLD has become a major chronic liver disease in China.Human epidemiological data suggest that estrogen has a protective effect on NASH in premenopausal women and that sex hormones influence the development of liver disease.This review focuses on the path-ogenesis,treatment,and relationship between NASH and other diseases as well as on the relationship between NASH and sex hormone metabolism,with the aim of providing new strategies for the treatment of NASH.展开更多
With the recent advances in neoantigen identification,peptide-based cancer vaccines offer substantial potential in the field of immunotherapy.However,rapid clearance,low immunogenicity,and insufficient antigen-present...With the recent advances in neoantigen identification,peptide-based cancer vaccines offer substantial potential in the field of immunotherapy.However,rapid clearance,low immunogenicity,and insufficient antigen-presenting cell(APC)uptake limit the efficacy of peptide-based cancer vaccines.This review explores the barriers hindering vaccine efficiency,highlights recent advancements in synthetic delivery systems,and features strategies for the key delivery steps of lymph node(LN)drainage,APC delivery,cross-presentation strategies,and adjuvant incorporation.This paper also discusses the design of preclinical studies evaluating vaccine efficiency,including vaccine administration routes and murine tumor models.展开更多
Objective:To prepare and characterize polycaprolactone(PCL)nanoparticles loaded with sonicator fragmented(SLA)and freeze-thaw Leishmania antigens(FTLA)and to investigate the in vitro immunogenicity of antigen-encapsul...Objective:To prepare and characterize polycaprolactone(PCL)nanoparticles loaded with sonicator fragmented(SLA)and freeze-thaw Leishmania antigens(FTLA)and to investigate the in vitro immunogenicity of antigen-encapsulated nanoparticles with calcium phosphate adjuvant.Methods:The water/oil/water binary emulsion solvent evaporation method was used to synthesize antigen-loaded PCL nanoparticles.Particles were characterized by scanning electron microscopy and zeta potential measurements.Their cytotoxicity in J774 macrophages in vitro was determined by MTT analysis.In addition,the amount of nitric oxide and the level of cytokines produced by macrophages were determined by Griess reaction and ELISA method,respectively.The protective effect of the developed formulations was evaluated by determining the infection index percentage in macrophages infected with Leishmania infantum.Results:Compared to the control group,SLA PCL and FTLA PCL nanoparticles with calcium phosphate adjuvant induced a 6-and 7-fold increase in nitric oxide,respectively.Additionally,the vaccine formulations promoted the production of IFN-γand IL-12.SLA PCL and FTLA PCL nanoparticles combined with calcium phosphate adjuvant caused an approximately 13-and 11-fold reduction in infection index,respectively,compared to the control group.Conclusions:The encapsulation of antigens obtained by both sonication and freeze-thawing into PCL nanoparticles and the formulations with calcium phosphate adjuvant show strong in vitro immune stimulating properties.Therefore,PCL-based antigen delivery systems and calcium phosphate adjuvant are recommended as a potential vaccine candidate against leishmaniasis.展开更多
Heterotopic ossification(HO)is a consequence of traumatic bone and tissue damage,which occurs in 65%of military casualties with blast-associated amputations.However,the mechanisms behind blast-induced HO remain unclea...Heterotopic ossification(HO)is a consequence of traumatic bone and tissue damage,which occurs in 65%of military casualties with blast-associated amputations.However,the mechanisms behind blast-induced HO remain unclear.Animal models are used to study blast-induced HO,but developing such models is challenging,particularly in how to use a pure blast wave(primary blast)to induce limb fracture that then requires an amputation.Several studies,including our recent study,have developed platforms to induce limb fractures in rats with blast loading or a mixture of blast and impact loading.However,these models are limited by the survivability of the animal and repeatability of the model.In this study,we developed an improved platform,aiming to improve the animal's survivability and injury repeatability as well as focusing on primary blast only.The platform exposed only one limb of the rat to a blast wave while providing proper protection to the rest of the rat's body.We obtained very consistent fracture outcome in the tibia(location and pattern)in cadaveric rats with a large range of size and weight.Importantly,the rats did not obviously move during the test,where movement is a potential cause of uncontrolled injury.We further conducted parametric studies by varying the features of the design of the platform.These factors,such as how the limb is fixed and how the cavity through which the limb is placed is sealed,significantly affect the resulting injury.This platform and test setups enable well-controlled limb fracture induced directly by pure blast wave,which is the fundamental step towards a complete in vivo animal model for blast-induced HO induced by primary blast alone,excluding secondary and tertiary blast injury.In addition,the platform design and the findings presented here,particularly regarding the proper protection of the animal,have implications for future studies investigating localized blast injuries,such as blast induced brain and lung injuries.展开更多
Polyploidy is a major factor in the evolution of plants,yet we know little about the origin and evolution of polyploidy in intertidal species.This study aimed to identify the evolutionary transitions in three truemang...Polyploidy is a major factor in the evolution of plants,yet we know little about the origin and evolution of polyploidy in intertidal species.This study aimed to identify the evolutionary transitions in three truemangrove species of the genus Acanthus distributed in the Indo-West Pacific region.For this purpose,we took an integrative approach that combined data on morphology,cytology,climatic niche,phylogeny,and biogeography of 493 samples from 42 geographic sites.Our results show that the Acanthus ilicifolius lineage distributed east of the Thai-Malay Peninsula possesses a tetraploid karyotype,which is morphologically distinct from that of the lineage on the west side.The haplotype networks and phylogenetic trees for the chloroplast genome and eight nuclear genes reveal that the tetraploid species has two sub-genomes,one each from A.ilicifolius and A.ebracteatus,the paternal and maternal parents,respectively.Population structure analysis also supports the hybrid speciation history of the new tetraploid species.The two sub-genomes of the tetraploid species diverged from their diploid progenitors during the Pleistocene.Environmental niche models revealed that the tetraploid species not only occupied the near-entire niche space of the diploids,but also expanded into novel environments.Our findings suggest that A.ilicifolius species distributed on the east side of the Thai-Malay Peninsula should be regarded as a new species,A.tetraploideus,which originated from hybridization between A.ilicifolius and A.ebracteatus,followed by chromosome doubling.This is the first report of a true-mangrove allopolyploid species that can reproduce sexually and clonally reproduction,which explains the long-term adaptive potential of the species.展开更多
Objective:To investigate the efficacy and safety of Liqingtong(LQT)granules in patients with dampness-heat hyperuricemia.Methods:A randomized,double-blind,placebo-controlled pilot trial was conducted at the 983rd Hos-...Objective:To investigate the efficacy and safety of Liqingtong(LQT)granules in patients with dampness-heat hyperuricemia.Methods:A randomized,double-blind,placebo-controlled pilot trial was conducted at the 983rd Hos-pital of the Joint Logistic Support Force of the People's Liberation Army from March 15,2023,to August 10,2023.In total,119 participants were enrolled in this trial,and participants were given either LQT granules or placebo for 60 days based on a health education.The primary outcome was serum uric acid(SUA)level,and the secondary outcome was the traditional Chinese medicine(TCM)symptom score,measured on days 0,30,and 60.Safety indicators,including liver function,kidney function,blood routine,glucose,blood lipid,blood pressure,and heart rate were tested on days 0 and 60 of the trial.The data were analyzed using Prism 9 software,and the significance level was set at P<0.05.Results:Among 119 participants,six in the LQT granule group and seven in the placebo group dropped out,and 106 participants completed clinical observation.Baseline information,including SUA levels,TCM symptom scores,and other clinical characteristics,did not differ between the groups.At the end of the trial,compared with baseline values,the SUA levels in the LQT granule group decreased(P<0.001),and no significant change was observed in the placebo group(P=0.422);compared with the placebo group,the SUA levels decreased in the LQT granule group(P=0.001).Compared with baseline values,the total TCM symptom scores in the LQT granule group decreased(P<0.001),with no change in the placebo group(P=0.136).Safety indicators did not differ significantly between the two groups.Conclusion:The pilot trial demonstrated the potential of LQT granules to lower SUA levels and improve symptoms of dampness and heat.展开更多
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.
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 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 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.
基金supported financially by“Kunlun Talents High-end Innovation and Entrepreneurship Talents”of Qinghai Province in 2022National Natural Science Foundation of China(Nos.22322401 and 82073816)Beijing Nova Program(No.20220484055)。
文摘Foods are often contaminated by multiple foodborne pathogens,which threatens human health.In this work,we developed a microfluidic biosensor for multiplex immunoassay of foodborne bacteria with agitation driven by programmed audio signals.This agitation,powered by the vibration of a speaker cone during music playing,accelerated the mass transport in the incubation process to form bacterial complexes within 10 min.Immunoassay reagents of the two target bacteria(Escherichia coli O157:H7 and Salmonella typhimurium)were preloaded into the corresponding fore-vacuum storage chamber on the chip,and released to participate in the subsequent immune analysis process by piercing the chambers.All the detection processes were integrated into a single microfluidic chip and controlled by a smartphone through Bluetooth.Under selected conditions,wide linear ranges and low limits of detection(LODs<2CFU/m L)were obtained,and real food samples were successfully determined within 30 min.This biosensing method can be extended to wide-ranging applications by loading different recognizing reagents.
基金financially supported by the Turkish Scientific and Technological Research Council(TUBITAK,No.TUBITAK-7218008)the Scientific Research Projects Unit of Istanbul Kultur University(No.IKU-BAP2212).
文摘This observational cohort study investigated the potential of a novel sperm-washing medium(SWM)enriched with serotonin(5-HT),L-carnitine(L-C),and coenzyme Q10(CoQ10)to enhance sperm motility and reduce DNA damage.It compared this innovative medium(5-HT/L-C/CoQ10 SWM)with two widely used commercial media(SWM 1 and SWM 2).Ninety-eight volunteers from an infertility clinic provided semen samples,which were divided into three aliquots for analysis in different SWMs:group 1,SWM was composed of hydroxyethyl piperazineethanesulfonic acid(HEPES),sodium bicarbonate,human serum albumin(HSA),taurine,and gentamicin sulfate(SWM 1);group 2,SWM was composed of HEPES,sodium bicarbonate,and HSA(SWM 2);and group 3,SWM was composed of HEPES-buffered human tubal fluid supplemented with 5-HT,L-C,and CoQ10(5-HT/L-C/CoQ10 SWM).Sperm motility was categorized as progressive,nonprogressive,or immotile.Apoptosis,reactive oxygen species(ROS)production,and DNA fragmentation were also assessed.There were no significant differences in total or progressive sperm motility among the groups.Spermatozoa in group 3 exhibited reduced apoptosis,necrosis,and ROS levels and increased viability.No significant differences were observed in the DNA fragmentation index among groups.The 5-HT/L-C/CoQ10 SWM reduced sperm oxidative stress and apoptosis compared with those of the two commercially available SWMs,suggesting that 5-HT/L-C/CoQ10 SWM could be useful for enhancing in vitro fertilization success rates.
基金Supported by the National Natural Science Foundation of China,No.81970529and the Natural Science Foundation of Jilin Province,No.20230508074RCand No.YDZJ202401218ZYTS.
文摘In this editorial,we comment on the article by Mei et al.Nonalcoholic steatohep-atitis(NASH)is a severe inflammatory subtype of nonalcoholic fatty liver disease(NAFLD)with pathological features including steatosis,hepatocellular damage,and varying degrees of fibrosis.With the epidemic of metabolic diseases and obesity,the prevalence of NAFLD in China has increased,and it is now similar to that in developed countries;thus,NAFLD has become a major chronic liver disease in China.Human epidemiological data suggest that estrogen has a protective effect on NASH in premenopausal women and that sex hormones influence the development of liver disease.This review focuses on the path-ogenesis,treatment,and relationship between NASH and other diseases as well as on the relationship between NASH and sex hormone metabolism,with the aim of providing new strategies for the treatment of NASH.
基金supported by the U.S.National Institutes of Health,National Cancer Institute Grant R01CA257563.
文摘With the recent advances in neoantigen identification,peptide-based cancer vaccines offer substantial potential in the field of immunotherapy.However,rapid clearance,low immunogenicity,and insufficient antigen-presenting cell(APC)uptake limit the efficacy of peptide-based cancer vaccines.This review explores the barriers hindering vaccine efficiency,highlights recent advancements in synthetic delivery systems,and features strategies for the key delivery steps of lymph node(LN)drainage,APC delivery,cross-presentation strategies,and adjuvant incorporation.This paper also discusses the design of preclinical studies evaluating vaccine efficiency,including vaccine administration routes and murine tumor models.
文摘Objective:To prepare and characterize polycaprolactone(PCL)nanoparticles loaded with sonicator fragmented(SLA)and freeze-thaw Leishmania antigens(FTLA)and to investigate the in vitro immunogenicity of antigen-encapsulated nanoparticles with calcium phosphate adjuvant.Methods:The water/oil/water binary emulsion solvent evaporation method was used to synthesize antigen-loaded PCL nanoparticles.Particles were characterized by scanning electron microscopy and zeta potential measurements.Their cytotoxicity in J774 macrophages in vitro was determined by MTT analysis.In addition,the amount of nitric oxide and the level of cytokines produced by macrophages were determined by Griess reaction and ELISA method,respectively.The protective effect of the developed formulations was evaluated by determining the infection index percentage in macrophages infected with Leishmania infantum.Results:Compared to the control group,SLA PCL and FTLA PCL nanoparticles with calcium phosphate adjuvant induced a 6-and 7-fold increase in nitric oxide,respectively.Additionally,the vaccine formulations promoted the production of IFN-γand IL-12.SLA PCL and FTLA PCL nanoparticles combined with calcium phosphate adjuvant caused an approximately 13-and 11-fold reduction in infection index,respectively,compared to the control group.Conclusions:The encapsulation of antigens obtained by both sonication and freeze-thawing into PCL nanoparticles and the formulations with calcium phosphate adjuvant show strong in vitro immune stimulating properties.Therefore,PCL-based antigen delivery systems and calcium phosphate adjuvant are recommended as a potential vaccine candidate against leishmaniasis.
基金the auspices of the Royal British Legion Centre for Blast Injury Studies at Imperial College Londonthe financial support of the Royal British Legion。
文摘Heterotopic ossification(HO)is a consequence of traumatic bone and tissue damage,which occurs in 65%of military casualties with blast-associated amputations.However,the mechanisms behind blast-induced HO remain unclear.Animal models are used to study blast-induced HO,but developing such models is challenging,particularly in how to use a pure blast wave(primary blast)to induce limb fracture that then requires an amputation.Several studies,including our recent study,have developed platforms to induce limb fractures in rats with blast loading or a mixture of blast and impact loading.However,these models are limited by the survivability of the animal and repeatability of the model.In this study,we developed an improved platform,aiming to improve the animal's survivability and injury repeatability as well as focusing on primary blast only.The platform exposed only one limb of the rat to a blast wave while providing proper protection to the rest of the rat's body.We obtained very consistent fracture outcome in the tibia(location and pattern)in cadaveric rats with a large range of size and weight.Importantly,the rats did not obviously move during the test,where movement is a potential cause of uncontrolled injury.We further conducted parametric studies by varying the features of the design of the platform.These factors,such as how the limb is fixed and how the cavity through which the limb is placed is sealed,significantly affect the resulting injury.This platform and test setups enable well-controlled limb fracture induced directly by pure blast wave,which is the fundamental step towards a complete in vivo animal model for blast-induced HO induced by primary blast alone,excluding secondary and tertiary blast injury.In addition,the platform design and the findings presented here,particularly regarding the proper protection of the animal,have implications for future studies investigating localized blast injuries,such as blast induced brain and lung injuries.
基金supported by grants from the National Natural Science Foundation of China (Grant Nos.32160051,42076117,and 41776166)Guangdong Basic and Applied Basic Research Foundation (Grant Nos.2022A1515012015,2023A1515012772)the Foreign Cultural and Educational Experts Project of the Ministry of Science and Technology (No.QNJ2021162001L)。
文摘Polyploidy is a major factor in the evolution of plants,yet we know little about the origin and evolution of polyploidy in intertidal species.This study aimed to identify the evolutionary transitions in three truemangrove species of the genus Acanthus distributed in the Indo-West Pacific region.For this purpose,we took an integrative approach that combined data on morphology,cytology,climatic niche,phylogeny,and biogeography of 493 samples from 42 geographic sites.Our results show that the Acanthus ilicifolius lineage distributed east of the Thai-Malay Peninsula possesses a tetraploid karyotype,which is morphologically distinct from that of the lineage on the west side.The haplotype networks and phylogenetic trees for the chloroplast genome and eight nuclear genes reveal that the tetraploid species has two sub-genomes,one each from A.ilicifolius and A.ebracteatus,the paternal and maternal parents,respectively.Population structure analysis also supports the hybrid speciation history of the new tetraploid species.The two sub-genomes of the tetraploid species diverged from their diploid progenitors during the Pleistocene.Environmental niche models revealed that the tetraploid species not only occupied the near-entire niche space of the diploids,but also expanded into novel environments.Our findings suggest that A.ilicifolius species distributed on the east side of the Thai-Malay Peninsula should be regarded as a new species,A.tetraploideus,which originated from hybridization between A.ilicifolius and A.ebracteatus,followed by chromosome doubling.This is the first report of a true-mangrove allopolyploid species that can reproduce sexually and clonally reproduction,which explains the long-term adaptive potential of the species.
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 efficacy and safety of Liqingtong(LQT)granules in patients with dampness-heat hyperuricemia.Methods:A randomized,double-blind,placebo-controlled pilot trial was conducted at the 983rd Hos-pital of the Joint Logistic Support Force of the People's Liberation Army from March 15,2023,to August 10,2023.In total,119 participants were enrolled in this trial,and participants were given either LQT granules or placebo for 60 days based on a health education.The primary outcome was serum uric acid(SUA)level,and the secondary outcome was the traditional Chinese medicine(TCM)symptom score,measured on days 0,30,and 60.Safety indicators,including liver function,kidney function,blood routine,glucose,blood lipid,blood pressure,and heart rate were tested on days 0 and 60 of the trial.The data were analyzed using Prism 9 software,and the significance level was set at P<0.05.Results:Among 119 participants,six in the LQT granule group and seven in the placebo group dropped out,and 106 participants completed clinical observation.Baseline information,including SUA levels,TCM symptom scores,and other clinical characteristics,did not differ between the groups.At the end of the trial,compared with baseline values,the SUA levels in the LQT granule group decreased(P<0.001),and no significant change was observed in the placebo group(P=0.422);compared with the placebo group,the SUA levels decreased in the LQT granule group(P=0.001).Compared with baseline values,the total TCM symptom scores in the LQT granule group decreased(P<0.001),with no change in the placebo group(P=0.136).Safety indicators did not differ significantly between the two groups.Conclusion:The pilot trial demonstrated the potential of LQT granules to lower SUA levels and improve symptoms of dampness and heat.
