BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,...BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains unclear.AIM To investigate the potential mechanism of action of LWWL against HBV.METHODS In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines.The in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV replication.Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.RESULTS In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,respectively.The inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,respectively.Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,P<0.05),HepG2.A64(4.89%±1.28%vs 8.52%±0.50%,P<0.05)and HepG2.1403F(3.76%±1.40%vs 7.57%±1.35%,P<0.05)(CG vs LWWL-treated group).However,there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells(5.04%±0.74%vs 5.51%±1.57%,P>0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model.CONCLUSION Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV,potentially involving selective regulation of apoptosis.These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.展开更多
Let k be a positive integer and G a bipartite graph with bipartition (X,Y). A perfect 1-k matching is an edge subset M of G such that each vertex in Y is incident with exactly one edge in M and each vertex in X is inc...Let k be a positive integer and G a bipartite graph with bipartition (X,Y). A perfect 1-k matching is an edge subset M of G such that each vertex in Y is incident with exactly one edge in M and each vertex in X is incident with exactly k edges in M. A perfect 1-k matching is an optimal semi-matching related to the load-balancing problem, where a semi-matching is an edge subset M such that each vertex in Y is incident with exactly one edge in M, and a vertex in X can be incident with an arbitrary number of edges in M. In this paper, we give three sufficient and necessary conditions for the existence of perfect 1-k matchings and for the existence of 1-k matchings covering | X |−dvertices in X, respectively, and characterize k-elementary bipartite graph which is a graph such that the subgraph induced by all k-allowed edges is connected, where an edge is k-allowed if it is contained in a perfect 1-k matching.展开更多
BACKGROUND Perineural invasion(PNI)has been used as an important pathological indicator and independent prognostic factor for patients with rectal cancer(RC).Preoperative prediction of PNI status is helpful for indivi...BACKGROUND Perineural invasion(PNI)has been used as an important pathological indicator and independent prognostic factor for patients with rectal cancer(RC).Preoperative prediction of PNI status is helpful for individualized treatment of RC.Recently,several radiomics studies have been used to predict the PNI status in RC,demonstrating a good predictive effect,but the results lacked generalizability.The preoperative prediction of PNI status is still challenging and needs further study.AIM To establish and validate an optimal radiomics model for predicting PNI status preoperatively in RC patients.METHODS This retrospective study enrolled 244 postoperative patients with pathologically confirmed RC from two independent centers.The patients underwent preoperative high-resolution magnetic resonance imaging(MRI)between May 2019 and August 2022.Quantitative radiomics features were extracted and selected from oblique axial T2-weighted imaging(T2WI)and contrast-enhanced T1WI(T1CE)sequences.The radiomics signatures were constructed using logistic regression analysis and the predictive potential of various sequences was compared(T2WI,T1CE and T2WI+T1CE fusion sequences).A clinical-radiomics(CR)model was established by combining the radiomics features and clinical risk factors.The internal and external validation groups were used to validate the proposed models.The area under the receiver operating characteristic curve(AUC),DeLong test,net reclassification improvement(NRI),integrated discrimination improvement(IDI),calibration curve,and decision curve analysis(DCA)were used to evaluate the model performance.RESULTS Among the radiomics models,the T2WI+T1CE fusion sequences model showed the best predictive performance,in the training and internal validation groups,the AUCs of the fusion sequence model were 0.839[95%confidence interval(CI):0.757-0.921]and 0.787(95%CI:0.650-0.923),which were higher than those of the T2WI and T1CE sequence models.The CR model constructed by combining clinical risk factors had the best predictive performance.In the training and internal and external validation groups,the AUCs of the CR model were 0.889(95%CI:0.824-0.954),0.889(95%CI:0.803-0.976)and 0.894(95%CI:0.814-0.974).Delong test,NRI,and IDI showed that the CR model had significant differences from other models(P<0.05).Calibration curves demonstrated good agreement,and DCA revealed significant benefits of the CR model.CONCLUSION The CR model based on preoperative MRI radiomics features and clinical risk factors can preoperatively predict the PNI status of RC noninvasively,which facilitates individualized treatment of RC patients.展开更多
The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alz...The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.展开更多
Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shel...Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.展开更多
In current practice of bolt reaming and anchoring of roadways in soft coal and rock mass,resin cartridges bend easily under the strong pushing and stirring of bolts,and the resin accumulates in the bolt-reamed area an...In current practice of bolt reaming and anchoring of roadways in soft coal and rock mass,resin cartridges bend easily under the strong pushing and stirring of bolts,and the resin accumulates in the bolt-reamed area and does not participate in the stirring.As a result,bolts encounter high drilling resistance and cannot reach the bottom of drillholes.The effective anchorage length is far less than the actual anchorage length.Bolts are not centered,and the shear is misaligned at the joint surface in the reaming area,which leads to cracking of the whole anchoring solid and large shear deformation of bolts.This study systematically analyzes the characteristics of roadway bolt reaming and anchoring.The influences of resin stirring force,bolt pull-out force,and reamingeanchoring solid strength on reamingeanchoring performance were analyzed theoretically.The main purpose is to develop a device that enhances reaming and anchoring.The mechanism through which the device strengthens the reamingeanchoring solid was analyzed theoretically.Numerical simulation and experiments were carried out to verify the improved performance of the small-pore reaming and anchoring using the proposed technology.The results showed that the stirring migration rate of the resin cartridge is greatly improved by adding the device to bolts.The reaction rate of the anchoring mixture,stirring pressure,pull-out force of the reaming and anchoring system,bolt concentricity,and shear and compressive strengths of the anchoring solid are also enhanced in the reaming area.This ensures that the resin cartridge in the reaming area is completely stirred,which greatly improves the shear resistance of the reamingeanchoring solid.Meanwhile,the drilling performance,torsional force,and stirring efficiency of bolts are maximized and prevail over those of conventional bolts.展开更多
AIM:To evaluate the relationship of overweight and obesity with retinal and choroidal thickness in adults without ocular symptoms by swept-source optical coherence tomography(SS-OCT).METHODS:According to the body mass...AIM:To evaluate the relationship of overweight and obesity with retinal and choroidal thickness in adults without ocular symptoms by swept-source optical coherence tomography(SS-OCT).METHODS:According to the body mass index(BMI)results,the adults enrolled in the cross-sectional study were divided into the normal group(18.50≤BMI<25.00 kg/m^(2)),the overweight group(25.00≤BMI<30.00 kg/m^(2)),and the obesity group(BMI≥30.00 kg/m^(2)).The one-way ANOVA and the Chi-square test were used for comparisons.Pearson’s correlation analysis was used to evaluate the relationships between the measured variables.RESULTS:This research covered the left eyes of 3 groups of 434 age-and sex-matched subjects each:normal,overweight,and obesity.The mean BMI was 22.20±1.67,26.82±1.38,and 32.21±2.35 kg/m^(2) in normal,overweight and obesity groups,respectively.The choroid was significantly thinner in both the overweight and obesity groups compared to the normal group(P<0.05 for all),while the retinal thickness of the three groups did not differ significantly.Pearson’s correlation analysis showed that BMI was significantly negatively correlated with choroidal thickness,but no significant correlation was observed between BMI and retinal thickness.CONCLUSION:Choroidal thickness is decreased in people with overweight or obesity.Research on changes in choroidal thickness contributes to the understanding of the mechanisms of certain ocular disorders in overweight and obese adults.展开更多
The majority of the projectiles used in the hypersonic penetration study are solid flat-nosed cylindrical projectiles with a diameter of less than 20 mm.This study aims to fill the gap in the experimental and analytic...The majority of the projectiles used in the hypersonic penetration study are solid flat-nosed cylindrical projectiles with a diameter of less than 20 mm.This study aims to fill the gap in the experimental and analytical study of the evolution of the nose shape of larger hollow projectiles under hypersonic penetration.In the hypersonic penetration test,eight ogive-nose AerMet100 steel projectiles with a diameter of 40 mm were launched to hit concrete targets with impact velocities that ranged from 1351 to 1877 m/s.Severe erosion of the projectiles was observed during high-speed penetration of heterogeneous targets,and apparent localized mushrooming occurred in the front nose of recovered projectiles.By examining the damage to projectiles,a linear relationship was found between the relative length reduction rate and the initial kinetic energy of projectiles in different penetration tests.Furthermore,microscopic analysis revealed the forming mechanism of the localized mushrooming phenomenon for eroding penetration,i.e.,material spall erosion abrasion mechanism,material flow and redistribution abrasion mechanism and localized radial upsetting deformation mechanism.Finally,a model of highspeed penetration that included erosion was established on the basis of a model of the evolution of the projectile nose that considers radial upsetting;the model was validated by test data from the literature and the present study.Depending upon the impact velocity,v0,the projectile nose may behave as undistorted,radially distorted or hemispherical.Due to the effects of abrasion of the projectile and enhancement of radial upsetting on the duration and amplitude of the secondary rising segment in the pulse shape of projectile deceleration,the predicted DOP had an upper limit.展开更多
Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children...Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.展开更多
Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomar...Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.展开更多
Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within...Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the brain.Lysosomes,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular homeostasis.Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s disease.Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease.Currently,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and targeting.Recently,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties.This review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s disease.This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function.In conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease.The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.展开更多
Prenatal overweight/obesity(OW/OB)can alter colostrum lipid patterns,thereby affecting the lipid metabolism and even the cognitive and healthy development of infants.However,studies on changes in colostrum lipids in t...Prenatal overweight/obesity(OW/OB)can alter colostrum lipid patterns,thereby affecting the lipid metabolism and even the cognitive and healthy development of infants.However,studies on changes in colostrum lipids in the context of OW/OB are limited,particularly for glycerides and polar lipids.Therefore,this study investigated the infl uence of maternal prenatal weight on colostrum in lipid subclasses and molecular species.The concentration of triacylglycerols(TAGs)in the colostrum of the OW/OB group(35894.43 mg/L)was higher than that of the normal weight(NW)group(26639.20 mg/L),suggesting that colostrum from OW/OB mothers could provide more energy to their infants.Further analysis of the fatty acid composition of TAGs revealed that elevated maternal body weight enhanced the concentration of TAGs containing saturated or n-6 fatty acids and shortened the carbon number of TAGs.Docosahexaenoic acid(DHA)/arachidonic acid(AA)/choline-containing lipids,such as DHA-containing TAGs,AA/DHA-containing phosphatidylethanolamine,and choline-containing phospholipids,were present in higher levels in the colostrum of OW/OB mothers than NW mothers.However,the concentrations of palmitic acid-containing TAGs,linoleic acid-containing TAGs,dihomo-γ-linolenic acid-containing TAGs,and polar lipids and the ratio of TAGs containing n-6 fatty acid/n-3 fatty acid were signifi cantly higher in the colostrum of OW/OB mothers than in that of NW mothers.The fatty acid composition and sphingoid bases of sphingolipids were also altered due to elevated body weight.In conclusion,OW/OB affects colostrum lipids with respect to composition,concentration,and percentage.Although the colostrum of healthy OW/OB mothers can provide suffi cient DHA/AA/choline-containing lipids to their infants,normalization of body weight and fat reserves should be considered as a strategy for highquality human milk lipids.展开更多
During our investigation of diatom biodiversity in Xizang,two species exhibited unique morphological features discriminative from all previously known genera.Herein we describe these two species and describe as new th...During our investigation of diatom biodiversity in Xizang,two species exhibited unique morphological features discriminative from all previously known genera.Herein we describe these two species and describe as new the genus,Spargeria gen.nov.The new genus features narrow to wide rectangular valves,narrow valve mantles,filiform raphe branches that occur on the valve face only,terminal raphe fissures straight or slightly deflected to same side,bow-tie shaped central areas,chambered striae present on the valve face only,being absent from the mantle,wider striae near the axial area and very narrow near the margin,multiseriate striae with small and round areolae that are occluded externally.Comparatively,Spargeria zhuii sp.nov.has larger and robust valves,radiate striae,with one divergent stria near the apices,while Spargeria chenia sp.nov.is smaller,with narrow valves,striae slightly radiate in the middle,becoming convergent or parallel near apices.This new genus belongs to the family Pinnulariaceae,and it was compared and contrasted with other genera of this family.Our work suggests the need for continued studies to document the biodiversity of diatoms in Xizang.展开更多
To achieve high energy density in lithium batteries,the construction of lithium-ion/metal hybrid anodes is a promising strategy.In particular,because of the anisotropy of graphite,hybrid anode formed by graphite/Li me...To achieve high energy density in lithium batteries,the construction of lithium-ion/metal hybrid anodes is a promising strategy.In particular,because of the anisotropy of graphite,hybrid anode formed by graphite/Li metal has low transport kinetics and is easy to causes the growth of lithium dendrites and accumulation of dead Li,which seriously affects the cycle life of batteries and even causes safety problems.Here,by comparing graphite with two types of hard carbon,it was found that hybrid anode formed by hard carbon and lithium metal,possessing more disordered mesoporous structure and lithophilic groups,presents better performance.Results indicate that the mesoporous structure provides abundant active site and storage space for dead lithium.With the synergistic effect of this structure and lithophilic functional groups(–COOH),the reversibility of hard carbon/lithium metal hybrid anode is maintained,promoting uniform deposition of lithium metal and alleviating formation of lithium dendrites.The hybrid anode maintains a 99.5%Coulombic efficiency(CE)after 260 cycles at a specific capacity of 500 m Ah/g.This work provides new insights into the hybrid anodes formed by carbon-based materials and lithium metal with high specific energy and fast charging ability.展开更多
Experimental scratch tests and first-principles calculations were used to investigate the adhesion property of AlCrNbSiTi high-entropy alloy(HEA)coatings on zirconium substrates.AlCrNbSiTi HEA and Cr coatings were dep...Experimental scratch tests and first-principles calculations were used to investigate the adhesion property of AlCrNbSiTi high-entropy alloy(HEA)coatings on zirconium substrates.AlCrNbSiTi HEA and Cr coatings were deposited on Zr alloy substrates using multi-arc ion plating technology,and scratch tests were subsequently conducted to estimate the adhesion property of the coatings.The results indicated that Cr coatings had better adhesion strength than HEA coatings,and the HEA coatings showed brittleness.The special quasi-random structure approach was used to build HEA models,and Cr/Zr and HEA/Zr interface models were employed to investigate the cohesion between the coatings and Zr substrate using first-principles calculations.The calculated interface energies showed that the cohesion between the Cr coating and the Zr substrate was stronger than that of the HEA coating with Zr.In contrary to Al or Si in the HEA coating,Cr,Nb,and Ti atoms binded strongly with Zr substrate.Based on the calculated elastic constants,it was found that low Cr and high Al content decreased the mechanical performances of HEA coatings.Finally,this study demonstrated the utilization of a combined approach involving first-principles calculations and experimental studies for future HEA coating development.展开更多
Limited research has been conducted on the influences of fiber content on close-in blasting characteristics for ultrahigh-performance fiber-reinforced concrete(UHPFRC)beams.This paper aims to address this knowledge ga...Limited research has been conducted on the influences of fiber content on close-in blasting characteristics for ultrahigh-performance fiber-reinforced concrete(UHPFRC)beams.This paper aims to address this knowledge gap through experimental and mesoscale numerical methods.Experiments were conducted on ten UHPFRC beams built with varying steel fiber volumetric fractions subjected to close-in explosive conditions.Additionally,this study considered other parameters,such as the longitudinal reinforcement type and ratio.In the case of UHPFRC beams featuring normal-strength longitudinal reinforcement of diametersΦ12,Φ16,andΦ20,a reduction in maximum displacement by magnitudes of19.6%,19.5%,and 17.4%was observed,respectively,as the volumetric fractions of fiber increased from1.0%to 2.5%.In addition,increasing the longitudinal reinforcement ratio and using high-strength steel longitudinal reinforcement both significantly reduced the deformation characteristics and increase the blasting resistances of UHPFRC beams.However,the effects on the local crushing and spalling damage were not significant.A mesoscale finite element model,which considers the impacts of fiber parameters on UHPFRC beam behaviors,was also established and well correlated with the test findings.Nevertheless,parametric analyses were further conducted to examine the impacts of the steel fiber content and length and the hybrid effects of various types of microfibers and steel fibers on the blasting performance of UHPFRC beams.展开更多
基金Supported by National Natural Science Foundation of China,No.81930110The National Funded Postdoctoral Researcher Program of China,No.GZC20232406+2 种基金Henan Province Traditional Chinese Medicine Science Research Project,No.2023ZY3040Henan Province Medical Science and Technology Research Plan Joint Construction Project,No.LHGJ20230233National Key Research and Development Program of China,No.2022YFC2303103.
文摘BACKGROUND Liuweiwuling Tablet(LWWL)is a Chinese patent medicine approved for the treatment of chronic inflammation caused by hepatitis B virus(HBV)infection.Previous studies have indicated an anti-HBV effect of LWWL,specifically in terms of antigen inhibition,but the underlying mechanism remains unclear.AIM To investigate the potential mechanism of action of LWWL against HBV.METHODS In vitro experiments utilized three HBV-replicating and three non-HBV-replicating cell lines.The in vivo experiment involved a hydrodynamic injectionmediated mouse model with HBV replication.Transcriptomics and metabolomics were used to investigate the underlying mechanisms of action of LWWL.RESULTS In HepG2.1403F cells,LWWL(0.8 mg/mL)exhibited inhibitory effects on HBV DNA,hepatitis B surface antigen and pregenomic RNA(pgRNA)at rates of 51.36%,24.74%and 50.74%,respectively.The inhibition rates of LWWL(0.8mg/mL)on pgRNA/covalently closed circular DNA in HepG2.1403F,HepG2.2.15 and HepG2.A64 cells were 47.78%,39.51%and 46.74%,respectively.Integration of transcriptomics and metabolomics showed that the anti-HBV effect of LWWL was primarily linked to pathways related to apoptosis(PI3K-AKT,CASP8-CASP3 and P53 pathways).Apoptosis flow analysis revealed that the apoptosis rate in the LWWL-treated group was significantly higher than in the control group(CG)among HBV-replicating cell lines,including HepG2.2.15(2.92%±1.01%vs 6.68%±2.04%,P<0.05),HepG2.A64(4.89%±1.28%vs 8.52%±0.50%,P<0.05)and HepG2.1403F(3.76%±1.40%vs 7.57%±1.35%,P<0.05)(CG vs LWWL-treated group).However,there were no significant differences in apoptosis rates between the non-HBV-replicating HepG2 cells(5.04%±0.74%vs 5.51%±1.57%,P>0.05),L02 cells(5.49%±0.80%vs 5.48%±1.01%,P>0.05)and LX2 cells(6.29%±1.54%vs 6.29%±0.88%,P>0.05).TUNEL staining revealed a significantly higher apoptosis rate in the LWWL-treated group than in the CG in the HBVreplicating mouse model,while no noticeable difference in apoptosis rates between the two groups was observed in the non-HBV-replicating mouse model.CONCLUSION Preliminary results suggest that LWWL exerts a potent inhibitory effect on wild-type and drug-resistant HBV,potentially involving selective regulation of apoptosis.These findings offer novel insights into the anti-HBV activities of LWWL and present a novel mechanism for the development of anti-HBV medications.
文摘Let k be a positive integer and G a bipartite graph with bipartition (X,Y). A perfect 1-k matching is an edge subset M of G such that each vertex in Y is incident with exactly one edge in M and each vertex in X is incident with exactly k edges in M. A perfect 1-k matching is an optimal semi-matching related to the load-balancing problem, where a semi-matching is an edge subset M such that each vertex in Y is incident with exactly one edge in M, and a vertex in X can be incident with an arbitrary number of edges in M. In this paper, we give three sufficient and necessary conditions for the existence of perfect 1-k matchings and for the existence of 1-k matchings covering | X |−dvertices in X, respectively, and characterize k-elementary bipartite graph which is a graph such that the subgraph induced by all k-allowed edges is connected, where an edge is k-allowed if it is contained in a perfect 1-k matching.
文摘BACKGROUND Perineural invasion(PNI)has been used as an important pathological indicator and independent prognostic factor for patients with rectal cancer(RC).Preoperative prediction of PNI status is helpful for individualized treatment of RC.Recently,several radiomics studies have been used to predict the PNI status in RC,demonstrating a good predictive effect,but the results lacked generalizability.The preoperative prediction of PNI status is still challenging and needs further study.AIM To establish and validate an optimal radiomics model for predicting PNI status preoperatively in RC patients.METHODS This retrospective study enrolled 244 postoperative patients with pathologically confirmed RC from two independent centers.The patients underwent preoperative high-resolution magnetic resonance imaging(MRI)between May 2019 and August 2022.Quantitative radiomics features were extracted and selected from oblique axial T2-weighted imaging(T2WI)and contrast-enhanced T1WI(T1CE)sequences.The radiomics signatures were constructed using logistic regression analysis and the predictive potential of various sequences was compared(T2WI,T1CE and T2WI+T1CE fusion sequences).A clinical-radiomics(CR)model was established by combining the radiomics features and clinical risk factors.The internal and external validation groups were used to validate the proposed models.The area under the receiver operating characteristic curve(AUC),DeLong test,net reclassification improvement(NRI),integrated discrimination improvement(IDI),calibration curve,and decision curve analysis(DCA)were used to evaluate the model performance.RESULTS Among the radiomics models,the T2WI+T1CE fusion sequences model showed the best predictive performance,in the training and internal validation groups,the AUCs of the fusion sequence model were 0.839[95%confidence interval(CI):0.757-0.921]and 0.787(95%CI:0.650-0.923),which were higher than those of the T2WI and T1CE sequence models.The CR model constructed by combining clinical risk factors had the best predictive performance.In the training and internal and external validation groups,the AUCs of the CR model were 0.889(95%CI:0.824-0.954),0.889(95%CI:0.803-0.976)and 0.894(95%CI:0.814-0.974).Delong test,NRI,and IDI showed that the CR model had significant differences from other models(P<0.05).Calibration curves demonstrated good agreement,and DCA revealed significant benefits of the CR model.CONCLUSION The CR model based on preoperative MRI radiomics features and clinical risk factors can preoperatively predict the PNI status of RC noninvasively,which facilitates individualized treatment of RC patients.
基金supported by the National Natural Science Foundation of China,Nos.82072051 and 81771964(both to JG)the Natural Science Foundation of Shanghai Municipal Science and Technology Commission,No.22ZR147750(to YY)+2 种基金Science and Technology Support Projects in Biomedicine Field of Shanghai Science and Technology Commission,No.19441907500(to YY)Innovative Clinical Research Project of Changzheng Hospital,No.2020 YLCYJ-Y02(to YY)Characteristic Medical Service Project for the Army of Changzheng Hospital,No.2020 CZWJFW12(to YY)。
文摘The current therapeutic drugs for Alzheimer's disease only improve symptoms,they do not delay disease progression.Therefo re,there is an urgent need for new effective drugs.The underlying pathogenic factors of Alzheimer's disease are not clear,but neuroinflammation can link various hypotheses of Alzheimer's disease;hence,targeting neuroinflammation may be a new hope for Alzheimer's disease treatment.Inhibiting inflammation can restore neuronal function,promote neuro regeneration,reduce the pathological burden of Alzheimer's disease,and improve or even reverse symptoms of Alzheimer's disease.This review focuses on the relationship between inflammation and various pathological hypotheses of Alzheimer's disease;reports the mechanisms and characteristics of small-molecule drugs(e.g.,nonsteroidal anti-inflammatory drugs,neurosteroids,and plant extracts);macromolecule drugs(e.g.,peptides,proteins,and gene therapeutics);and nanocarriers(e.g.,lipid-based nanoparticles,polymeric nanoparticles,nanoemulsions,and inorganic nanoparticles)in the treatment of Alzheimer's disease.The review also makes recommendations for the prospective development of anti-inflammatory strategies based on nanocarriers for the treatment of Alzheimer's disease.
基金supported by the Natural Science Foundation of Fujian Province of China(No.2022J01043)China Scholarship Council(201806315005 and 201703170071).
文摘Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.
基金supported by the National Natural Science Foundation of China-Liaoning Joint Fund Key Project(Grant No.U1908222)the National Natural Science Foundation of China Youth Science Fund(Grant No.52104087).
文摘In current practice of bolt reaming and anchoring of roadways in soft coal and rock mass,resin cartridges bend easily under the strong pushing and stirring of bolts,and the resin accumulates in the bolt-reamed area and does not participate in the stirring.As a result,bolts encounter high drilling resistance and cannot reach the bottom of drillholes.The effective anchorage length is far less than the actual anchorage length.Bolts are not centered,and the shear is misaligned at the joint surface in the reaming area,which leads to cracking of the whole anchoring solid and large shear deformation of bolts.This study systematically analyzes the characteristics of roadway bolt reaming and anchoring.The influences of resin stirring force,bolt pull-out force,and reamingeanchoring solid strength on reamingeanchoring performance were analyzed theoretically.The main purpose is to develop a device that enhances reaming and anchoring.The mechanism through which the device strengthens the reamingeanchoring solid was analyzed theoretically.Numerical simulation and experiments were carried out to verify the improved performance of the small-pore reaming and anchoring using the proposed technology.The results showed that the stirring migration rate of the resin cartridge is greatly improved by adding the device to bolts.The reaction rate of the anchoring mixture,stirring pressure,pull-out force of the reaming and anchoring system,bolt concentricity,and shear and compressive strengths of the anchoring solid are also enhanced in the reaming area.This ensures that the resin cartridge in the reaming area is completely stirred,which greatly improves the shear resistance of the reamingeanchoring solid.Meanwhile,the drilling performance,torsional force,and stirring efficiency of bolts are maximized and prevail over those of conventional bolts.
基金Supported by the Science and Technology Commission of Shanghai Municipality(No.20Y11910800).
文摘AIM:To evaluate the relationship of overweight and obesity with retinal and choroidal thickness in adults without ocular symptoms by swept-source optical coherence tomography(SS-OCT).METHODS:According to the body mass index(BMI)results,the adults enrolled in the cross-sectional study were divided into the normal group(18.50≤BMI<25.00 kg/m^(2)),the overweight group(25.00≤BMI<30.00 kg/m^(2)),and the obesity group(BMI≥30.00 kg/m^(2)).The one-way ANOVA and the Chi-square test were used for comparisons.Pearson’s correlation analysis was used to evaluate the relationships between the measured variables.RESULTS:This research covered the left eyes of 3 groups of 434 age-and sex-matched subjects each:normal,overweight,and obesity.The mean BMI was 22.20±1.67,26.82±1.38,and 32.21±2.35 kg/m^(2) in normal,overweight and obesity groups,respectively.The choroid was significantly thinner in both the overweight and obesity groups compared to the normal group(P<0.05 for all),while the retinal thickness of the three groups did not differ significantly.Pearson’s correlation analysis showed that BMI was significantly negatively correlated with choroidal thickness,but no significant correlation was observed between BMI and retinal thickness.CONCLUSION:Choroidal thickness is decreased in people with overweight or obesity.Research on changes in choroidal thickness contributes to the understanding of the mechanisms of certain ocular disorders in overweight and obese adults.
基金the National Natural Science Foundation of China(Grant No.12102050)the Open Fund of State Key Laboratory of Explosion Science and Technology(Grant No.SKLEST-ZZ-21-18).
文摘The majority of the projectiles used in the hypersonic penetration study are solid flat-nosed cylindrical projectiles with a diameter of less than 20 mm.This study aims to fill the gap in the experimental and analytical study of the evolution of the nose shape of larger hollow projectiles under hypersonic penetration.In the hypersonic penetration test,eight ogive-nose AerMet100 steel projectiles with a diameter of 40 mm were launched to hit concrete targets with impact velocities that ranged from 1351 to 1877 m/s.Severe erosion of the projectiles was observed during high-speed penetration of heterogeneous targets,and apparent localized mushrooming occurred in the front nose of recovered projectiles.By examining the damage to projectiles,a linear relationship was found between the relative length reduction rate and the initial kinetic energy of projectiles in different penetration tests.Furthermore,microscopic analysis revealed the forming mechanism of the localized mushrooming phenomenon for eroding penetration,i.e.,material spall erosion abrasion mechanism,material flow and redistribution abrasion mechanism and localized radial upsetting deformation mechanism.Finally,a model of highspeed penetration that included erosion was established on the basis of a model of the evolution of the projectile nose that considers radial upsetting;the model was validated by test data from the literature and the present study.Depending upon the impact velocity,v0,the projectile nose may behave as undistorted,radially distorted or hemispherical.Due to the effects of abrasion of the projectile and enhancement of radial upsetting on the duration and amplitude of the secondary rising segment in the pulse shape of projectile deceleration,the predicted DOP had an upper limit.
基金supported by the National Natural Science Foundation of China(82171001,82222015)Research Funding from West China School/Hospital of Stomatology Sichuan University(RCDWJS2023-1)Align Technology Specialized Scientific Research Fund(21H0922).
文摘Malocclusion,identified by the World Health Organization(WHO)as one of three major oral diseases,profoundly impacts the dental-maxillofacial functions,facial esthetics,and long-term development of~260 million children in China.Beyond its physical manifestations,malocclusion also significantly influences the psycho-social well-being of these children.Timely intervention in malocclusion can foster an environment conducive to dental-maxillofacial development and substantially decrease the incidence of malocclusion or reduce the severity and complexity of malocclusion in the permanent dentition,by mitigating the negative impact of abnormal environmental influences on the growth.Early orthodontic treatment encompasses accurate identification and treatment of dental and maxillofacial morphological and functional abnormalities during various stages of dental-maxillofacial development,ranging from fetal stages to the early permanent dentition phase.From an economic and societal standpoint,the urgency for effective early orthodontic treatments for malocclusions in childhood cannot be overstated,underlining its profound practical and social importance.This consensus paper discusses the characteristics and the detrimental effects of malocclusion in children,emphasizing critical need for early treatment.It elaborates on corresponding core principles and fundamental approaches in early orthodontics,proposing comprehensive guidance for preventive and interceptive orthodontic treatment,serving as a reference for clinicians engaged in early orthodontic treatment.
基金supported by the Collaborative Innovation Center for Clinical and Translational Science by Chinese Ministry of Education&Shanghai,No.CCTS-2022205the“Double World-Class Project”of Shanghai Jiaotong University School of Medicine(both to JZ)。
文摘Spinal muscular atrophy is a devastating motor neuron disease characterized by severe cases of fatal muscle weakness.It is one of the most common genetic causes of mortality among infants aged less than 2 years.Biomarker research is currently receiving more attention,and new candidate biomarkers are constantly being discovered.This review initially discusses the evaluation methods commonly used in clinical practice while briefly outlining their respective pros and cons.We also describe recent advancements in research and the clinical significance of molecular biomarkers for spinal muscular atrophy,which are classified as either specific or non-specific biomarkers.This review provides new insights into the pathogenesis of spinal muscular atrophy,the mechanism of biomarkers in response to drug-modified therapies,the selection of biomarker candidates,and would promote the development of future research.Furthermore,the successful utilization of biomarkers may facilitate the implementation of gene-targeting treatments for patients with spinal muscular atrophy.
基金supported by the Natural Science Foundation of Shanghai,No.22ZR147750Science and Technology Innovation Action Plan of Shanghai Science and Technology Commission,No.23Y11906600Shanghai Changzheng Hospital Innovative Clinical Research Project,No.2020YLCYJ-Y02(all to YY).
文摘Alzheimer’s disease is a debilitating,progressive neurodegenerative disorder characterized by the progressive accumulation of abnormal proteins,including amyloid plaques and intracellular tau tangles,primarily within the brain.Lysosomes,crucial intracellular organelles responsible for protein degradation,play a key role in maintaining cellular homeostasis.Some studies have suggested a link between the dysregulation of the lysosomal system and pathogenesis of neurodegenerative diseases,including Alzheimer’s disease.Restoring the normal physiological function of lysosomes hold the potential to reduce the pathological burden and improve the symptoms of Alzheimer’s disease.Currently,the efficacy of drugs in treating Alzheimer’s disease is limited,with major challenges in drug delivery efficiency and targeting.Recently,nanomaterials have gained widespread use in Alzheimer’s disease drug research owing to their favorable physical and chemical properties.This review aims to provide a comprehensive overview of recent advances in using nanomaterials(polymeric nanomaterials,nanoemulsions,and carbon-based nanomaterials)to enhance lysosomal function in treating Alzheimer’s disease.This review also explores new concepts and potential therapeutic strategies for Alzheimer’s disease through the integration of nanomaterials and modulation of lysosomal function.In conclusion,this review emphasizes the potential of nanomaterials in modulating lysosomal function to improve the pathological features of Alzheimer’s disease.The application of nanotechnology to the development of Alzheimer’s disease drugs brings new ideas and approaches for future treatment of this disease.
基金supported by the Guangxi Science and Technology Project(AD20297088)the National Natural Science Foundation of China(32272316),and the Beijing Innovation Team of Livestock Industry Technology System(BAIC05-2022).
文摘Prenatal overweight/obesity(OW/OB)can alter colostrum lipid patterns,thereby affecting the lipid metabolism and even the cognitive and healthy development of infants.However,studies on changes in colostrum lipids in the context of OW/OB are limited,particularly for glycerides and polar lipids.Therefore,this study investigated the infl uence of maternal prenatal weight on colostrum in lipid subclasses and molecular species.The concentration of triacylglycerols(TAGs)in the colostrum of the OW/OB group(35894.43 mg/L)was higher than that of the normal weight(NW)group(26639.20 mg/L),suggesting that colostrum from OW/OB mothers could provide more energy to their infants.Further analysis of the fatty acid composition of TAGs revealed that elevated maternal body weight enhanced the concentration of TAGs containing saturated or n-6 fatty acids and shortened the carbon number of TAGs.Docosahexaenoic acid(DHA)/arachidonic acid(AA)/choline-containing lipids,such as DHA-containing TAGs,AA/DHA-containing phosphatidylethanolamine,and choline-containing phospholipids,were present in higher levels in the colostrum of OW/OB mothers than NW mothers.However,the concentrations of palmitic acid-containing TAGs,linoleic acid-containing TAGs,dihomo-γ-linolenic acid-containing TAGs,and polar lipids and the ratio of TAGs containing n-6 fatty acid/n-3 fatty acid were signifi cantly higher in the colostrum of OW/OB mothers than in that of NW mothers.The fatty acid composition and sphingoid bases of sphingolipids were also altered due to elevated body weight.In conclusion,OW/OB affects colostrum lipids with respect to composition,concentration,and percentage.Although the colostrum of healthy OW/OB mothers can provide suffi cient DHA/AA/choline-containing lipids to their infants,normalization of body weight and fat reserves should be considered as a strategy for highquality human milk lipids.
基金the National Natural Science Foundation of China(Nos.31970213,31870187)the Natural Science Foundation of Heilongjiang Province for Excellent Young Scholars(No.YQ2020C032)the Second Tibetan Plateau Scientific Expedition and Research Program(No.2019QZKK0304)。
文摘During our investigation of diatom biodiversity in Xizang,two species exhibited unique morphological features discriminative from all previously known genera.Herein we describe these two species and describe as new the genus,Spargeria gen.nov.The new genus features narrow to wide rectangular valves,narrow valve mantles,filiform raphe branches that occur on the valve face only,terminal raphe fissures straight or slightly deflected to same side,bow-tie shaped central areas,chambered striae present on the valve face only,being absent from the mantle,wider striae near the axial area and very narrow near the margin,multiseriate striae with small and round areolae that are occluded externally.Comparatively,Spargeria zhuii sp.nov.has larger and robust valves,radiate striae,with one divergent stria near the apices,while Spargeria chenia sp.nov.is smaller,with narrow valves,striae slightly radiate in the middle,becoming convergent or parallel near apices.This new genus belongs to the family Pinnulariaceae,and it was compared and contrasted with other genera of this family.Our work suggests the need for continued studies to document the biodiversity of diatoms in Xizang.
基金Financial support from the National Natural Science Foundation of China (22075320)。
文摘To achieve high energy density in lithium batteries,the construction of lithium-ion/metal hybrid anodes is a promising strategy.In particular,because of the anisotropy of graphite,hybrid anode formed by graphite/Li metal has low transport kinetics and is easy to causes the growth of lithium dendrites and accumulation of dead Li,which seriously affects the cycle life of batteries and even causes safety problems.Here,by comparing graphite with two types of hard carbon,it was found that hybrid anode formed by hard carbon and lithium metal,possessing more disordered mesoporous structure and lithophilic groups,presents better performance.Results indicate that the mesoporous structure provides abundant active site and storage space for dead lithium.With the synergistic effect of this structure and lithophilic functional groups(–COOH),the reversibility of hard carbon/lithium metal hybrid anode is maintained,promoting uniform deposition of lithium metal and alleviating formation of lithium dendrites.The hybrid anode maintains a 99.5%Coulombic efficiency(CE)after 260 cycles at a specific capacity of 500 m Ah/g.This work provides new insights into the hybrid anodes formed by carbon-based materials and lithium metal with high specific energy and fast charging ability.
基金supported by Stability Supports Research Project of Treasury Department(No.197801)Talent Fund of CIAE(No.219213)。
文摘Experimental scratch tests and first-principles calculations were used to investigate the adhesion property of AlCrNbSiTi high-entropy alloy(HEA)coatings on zirconium substrates.AlCrNbSiTi HEA and Cr coatings were deposited on Zr alloy substrates using multi-arc ion plating technology,and scratch tests were subsequently conducted to estimate the adhesion property of the coatings.The results indicated that Cr coatings had better adhesion strength than HEA coatings,and the HEA coatings showed brittleness.The special quasi-random structure approach was used to build HEA models,and Cr/Zr and HEA/Zr interface models were employed to investigate the cohesion between the coatings and Zr substrate using first-principles calculations.The calculated interface energies showed that the cohesion between the Cr coating and the Zr substrate was stronger than that of the HEA coating with Zr.In contrary to Al or Si in the HEA coating,Cr,Nb,and Ti atoms binded strongly with Zr substrate.Based on the calculated elastic constants,it was found that low Cr and high Al content decreased the mechanical performances of HEA coatings.Finally,this study demonstrated the utilization of a combined approach involving first-principles calculations and experimental studies for future HEA coating development.
基金supported by the National Natural Science Foundation of China(Grant No.12102050)the Open Fund of State Key Laboratory of Explosion Science and Technology(Grant No.SKLEST-ZZ-21-18)。
文摘Limited research has been conducted on the influences of fiber content on close-in blasting characteristics for ultrahigh-performance fiber-reinforced concrete(UHPFRC)beams.This paper aims to address this knowledge gap through experimental and mesoscale numerical methods.Experiments were conducted on ten UHPFRC beams built with varying steel fiber volumetric fractions subjected to close-in explosive conditions.Additionally,this study considered other parameters,such as the longitudinal reinforcement type and ratio.In the case of UHPFRC beams featuring normal-strength longitudinal reinforcement of diametersΦ12,Φ16,andΦ20,a reduction in maximum displacement by magnitudes of19.6%,19.5%,and 17.4%was observed,respectively,as the volumetric fractions of fiber increased from1.0%to 2.5%.In addition,increasing the longitudinal reinforcement ratio and using high-strength steel longitudinal reinforcement both significantly reduced the deformation characteristics and increase the blasting resistances of UHPFRC beams.However,the effects on the local crushing and spalling damage were not significant.A mesoscale finite element model,which considers the impacts of fiber parameters on UHPFRC beam behaviors,was also established and well correlated with the test findings.Nevertheless,parametric analyses were further conducted to examine the impacts of the steel fiber content and length and the hybrid effects of various types of microfibers and steel fibers on the blasting performance of UHPFRC beams.