Objectives:The pro-oncogenic effects of NCAPD2 have been extensively studied across various tumor types;however,its precise role within the context of lung adenocarcinoma(LUAD)remains elusive.This study aims to elucid...Objectives:The pro-oncogenic effects of NCAPD2 have been extensively studied across various tumor types;however,its precise role within the context of lung adenocarcinoma(LUAD)remains elusive.This study aims to elucidate the biological functions of NCAPD2 in LUAD and unravel the underlying mechanistic pathways.Methods:Utilizing bioinformatics methodologies,we explored the differential expression of NCAPD2 between normal and tumor samples,along with its correlations with clinical-pathological characteristics,survival prognosis,and immune infiltration.Results:In the TCGA-LUAD dataset,tumor samples demonstrated significantly elevated levels of NCAPD2 expression compared to normal samples(p<0.001).Clinically,higher NCAPD2 expression was notably associated with advanced T,N,and M stages,pathologic stage,gender,smoking status,and diminished overall survival(OS).Moreover,differentially expressed genes(DEGs)associated with NCAPD2 were predominantly enriched in pathways related to cell division.Immune infiltration analysis revealed that NCAPD2 expression levels were linked to the infiltration of memory B cells,naïve CD4+T cells,activated memory CD4+T cells,and M1 macrophages.In vitro experiments demonstrated that silencing NCAPD2 suppressed LUAD cell proliferation,migration,invasion,epithelial-mesenchymal transition(EMT),and cell cycle progression.Conclusions:In summary,NCAPD2 may represent a promising prognostic biomarker and novel therapeutic target for LUAD.展开更多
Objective:To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms.Methods:The effects of Hydrangea serrata extract on growth inhibition ...Objective:To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms.Methods:The effects of Hydrangea serrata extract on growth inhibition of tumor cells and spheroids were assessed using MTT and 3D culture assays.Quantitative real-time PCR and Western blot analyses were employed to investigate the changes in mRNA and protein expression levels of molecules related to cell cycle and apoptosis.Results:Hydrangea serrata extract effectively inhibited the growth of both tumor cells and spheroids.The extract also significantly upregulated p27 mRNA expression and downregulated CDK2 mRNA expression,leading to cell cycle arrest.Moreover,increased BAX/Bcl-2 ratio as well as caspase-9 and-3 were observed after treatment with Hydrangea serrata extract,indicating the induction of tumor cell apoptosis.Conclusions:Hydrangea serrata extract has the potential to alleviate tumors by effectively modulating cell-cycle-related gene expressions and inducing apoptosis,thereby inhibiting tumor growth.展开更多
Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential ...Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.展开更多
Krill oil(KO)exhibits various biological activities,such as anti-inflammatory and antitumor effects.However,the inhibitory effects of benign prostatic hyperplasia(BPH)in vitro and in vivo have not yet been studied.Thi...Krill oil(KO)exhibits various biological activities,such as anti-inflammatory and antitumor effects.However,the inhibitory effects of benign prostatic hyperplasia(BPH)in vitro and in vivo have not yet been studied.This study investigated the anti-BPH effects of KO extracted by an enzymatic hydrolysis method.KO treatment inhibited the proliferation of WMPY-1 and BPH-1 cells by induction of G0/G1 phase arrest through the modulation of positive and negative regulators in both prostate cell types.KO treatment stimulated phosphorylation of c-Jun N-terminal kinase(JNK)and p38 signaling.In addition,KO changed the expression of BPH-related markers(5α-reductase,androgen receptor,FGF,Bcl-2,and Bax)and the activity of the proliferation-mediated NF-κB binding motif.KO-induced levels of proliferation-mediated molecules of prostate cells were attenuated in the presence of siRNA-specific p-38(si-p38)and JNK(si-JNK).Furthermore,the administration of KO alleviated prostate size and weight and the cell layer thickness of prostate glands in a testosterone enanthate-induced BPH rat model.KO treatment altered the level of dihydrotestosterone in serum and the expression levels of BPH-related markers in prostate tissues.Finally,KO-mediated inhibition of prostatic growth was validated by histological analysis.These results suggest that KO has an inhibitory effect on BPH in prostate cells in vitro and in vivo.Thus,KO might be a potential prophylactic or therapeutic agent for patients with BPH.展开更多
This study aims to evaluate the effect of serum concentration, synchronization time, and confluence degree on the synchronisation efficiency of goat fibroblast cycle. The results indicated that there was no difference...This study aims to evaluate the effect of serum concentration, synchronization time, and confluence degree on the synchronisation efficiency of goat fibroblast cycle. The results indicated that there was no difference in the percentage of nucleated fibroblasts in the G0/G1 stage between serum concentrations of 0.3% and 0.4% (83.89% and 82.69%, respectively, P > 0.05) as well as between serum concentrations of 0.2% and 0.5% (76.95% and 75.46%, respectively, P > 0.05). The percentage of nucleated fibroblasts in the G0/G1 stage was highest at the concentration of 0.3% and lowest in the control group (83.89% vs. 62.67%, P 0.05). The beneficial effect of high confluence was confirmed by the large percentage of nucleated fibroblasts at the G0/G1 stage. The 60% confluency was significantly lower than the 80% and 100% confluency (73.44%, 86.63%, and 87.17%, respectively, P < 0.05). The results indicate that the goat fibroblast cycle synchronization is the most effective at the serum concentration of 0.3%, 72 hours of synchronization and 100% confluency.展开更多
A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the mol...A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the molten salt reactor and power system.This model considers the impact of thermal properties of fluid variation on accuracy and has been validated with Simulink.This study reveals the capability of the control system to compensate for anomalous situations and maintain shaft stability in the event of perturbations occurring in high-temperature molten salt tank outlet parameters.Meanwhile,the control system’s impact on the system’s dynamic characteristics under molten salt disturbance is also analyzed.The results reveal that after the disturbance occurs,the controlled system benefits from the action of the control,and the overshoot and disturbance amplitude are positively correlated,while the system power and frequency eventually return to the initial values.This simulation model provides a basis for utilizing molten salt reactors for power generation and maintaining grid stability.展开更多
Enzyme-induced carbonate precipitation(EICP)is an emanating,eco-friendly and potentially sound technique that has presented promise in various geotechnical applications.However,the durability and microscopic character...Enzyme-induced carbonate precipitation(EICP)is an emanating,eco-friendly and potentially sound technique that has presented promise in various geotechnical applications.However,the durability and microscopic characteristics of EICP-treated specimens against the impact of drying-wetting(D-W)cycles is under-explored yet.This study investigates the evolution of mechanical behavior and pore charac-teristics of EICP-treated sea sand subjected to D-W cycles.The uniaxial compressive strength(UCS)tests,synchrotron radiation micro-computed tomography(micro-CT),and three-dimensional(3D)recon-struction of CT images were performed to study the multiscale evolution characteristics of EICP-reinforced sea sand under the effect of D-W cycles.The potential correlations between microstructure characteristics and macro-mechanical property deterioration were investigated using gray relational analysis(GRA).Results showed that the UCS of EICP-treated specimens decreases by 63.7% after 15 D-W cycles.The proportion of mesopores gradually decreases whereas the proportion of macropores in-creases due to the exfoliated calcium carbonate with increasing number of D-W cycles.The micro-structure in EICP-reinforced sea sand was gradually disintegrated,resulting in increasing pore size and development of pore shape from ellipsoidal to columnar and branched.The gray relational degree suggested that the weight loss rate and UCS deterioration were attributed to the development of branched pores with a size of 100-1000 m m under the action of D-W cycles.Overall,the results in this study provide a useful guidancee for the long-term stability and evolution characteristics of EICP-reinforced sea sand under D-W weathering conditions.展开更多
Currently,the major challenge in terms of research on K-ion batteries is to ensure that they possess satisfactory cycle stability and specific capacity,especially in terms of the intrinsically sluggish kinetics induce...Currently,the major challenge in terms of research on K-ion batteries is to ensure that they possess satisfactory cycle stability and specific capacity,especially in terms of the intrinsically sluggish kinetics induced by the large radius of K+ions.Here,we explore high-performance K-ion half/full batteries with high rate capability,high specific capacity,and extremely durable cycle stability based on carbon nanosheets with tailored N dopants,which can alleviate the change of volume,increase electronic conductivity,and enhance the K+ion adsorption.The as-assembled K-ion half-batteries show an excellent rate capability of 468 mA h g^(−1) at 100 mA g^(−1),which is superior to those of most carbon materials reported to date.Moreover,the as-assembled half-cells have an outstanding life span,running 40,000 cycles over 8 months with a specific capacity retention of 100%at a high current density of 2000 mA g^(−1),and the target full cells deliver a high reversible specific capacity of 146 mA h g^(−1) after 2000 cycles over 2 months,with a specific capacity retention of 113%at a high current density of 500 mA g^(−1),both of which are state of the art in the field of K-ion batteries.This study might provide some insights into and potential avenues for exploration of advanced K-ion batteries with durable stability for practical applications.展开更多
The supercritical CO_(2) Brayton cycle is considered a promising energy conversion system for Generation IV reactors for its simple layout,compact structure,and high cycle efficiency.Mathematical models of four Brayto...The supercritical CO_(2) Brayton cycle is considered a promising energy conversion system for Generation IV reactors for its simple layout,compact structure,and high cycle efficiency.Mathematical models of four Brayton cycle layouts are developed in this study for different reactors to reduce the cost and increase the thermohydraulic performance of nuclear power generation to promote the commercialization of nuclear energy.Parametric analysis,multi-objective optimizations,and four decision-making methods are applied to obtain each Brayton scheme’s optimal thermohydraulic and economic indexes.Results show that for the same design thermal power scale of reactors,the higher the core’s exit temperature,the better the Brayton cycle’s thermo-economic performance.Among the four-cycle layouts,the recompression cycle(RC)has the best overall performance,followed by the simple recuperation cycle(SR)and the intercooling cycle(IC),and the worst is the reheating cycle(RH).However,RH has the lowest total cost of investment(C_(tot))of$1619.85 million,and IC has the lowest levelized cost of energy(LCOE)of 0.012$/(kWh).The nuclear Brayton cycle system’s overall performance has been improved due to optimization.The performance of the molten salt reactor combined with the intercooling cycle(MSR-IC)scheme has the greatest improvement,with the net output power(W_(net)),thermal efficiencyη_(t),and exergy efficiency(η_(e))improved by 8.58%,8.58%,and 11.21%,respectively.The performance of the lead-cooled fast reactor combined with the simple recuperation cycle scheme was optimized to increase C_(tot) by 27.78%.In comparison,the internal rate of return(IRR)increased by only 7.8%,which is not friendly to investors with limited funds.For the nuclear Brayton cycle,the molten salt reactor combined with the recompression cycle scheme should receive priority,and the gas-cooled fast reactor combined with the reheating cycle scheme should be considered carefully.展开更多
Abscisic acid(ABA),hydrogen peroxide(H_(2)O_(2)) and ascorbate(AsA)–glutathione(GSH)cycle are widely known for their participation in various stresses.However,the relationship between ABA and H_(2)O_(2) levels and th...Abscisic acid(ABA),hydrogen peroxide(H_(2)O_(2)) and ascorbate(AsA)–glutathione(GSH)cycle are widely known for their participation in various stresses.However,the relationship between ABA and H_(2)O_(2) levels and the AsA–GSH cycle under drought stress in wheat has not been studied.In this study,a hydroponic experiment was conducted in wheat seedlings subjected to 15%polyethylene glycol(PEG)6000–induced dehydration.Drought stress caused the rapid accumulation of endogenous ABA and H_(2)O_(2) and significantly decreased the number of root tips compared with the control.The application of ABA significantly increased the number of root tips,whereas the application of H_(2)O_(2) markedly reduced the number of root tips,compared with that under 15%PEG-6000.In addition,drought stress markedly increased the DHA,GSH and GSSG levels,but decreased the AsA levels,AsA/DHA and GSH/GSSG ratios compared with those in the control.The activities of the four enzymes in the AsA–GSH cycle were also markedly increased under drought stress,including glutathione reductase(GR),ascorbate peroxidase(APX),monodehydroascorbate reductase(MDHAR)and dehydroascorbate reductase(DHAR),compared with those in the control.However,the application of an ABA inhibitor significantly inhibited GR,DHAR and APX activities,whereas the application of an H_(2)O_(2) inhibitor significantly inhibited DHAR and MDHAR activities.Furthermore,the application of ABA inhibitor significantly promoted the increases of H_(2)O_(2) and the application of H_(2)O_(2) inhibitor significantly blocked the increases of ABA,compared with those under 15% PEG-6000.Taken together,the results indicated that ABA and H_(2)O_(2) probably interact under drought stress in wheat;and both of them can mediate drought stress by modulating the enzymes in AsA–GSH cycle,where ABA acts as the main regulator of GR,DHAR,and APX activities,and H_(2)O_(2) acts as the main regulator of DHAR and MDHAR activities.展开更多
Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate...Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.展开更多
Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is...Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.展开更多
Polyphenol-rich foods have been shown to be good for cancer prevention as powerful antioxidants. In this study, the mechanisms of wild pink bayberry free phenolic extract(WPBFE)inhibiting the proliferation and inducin...Polyphenol-rich foods have been shown to be good for cancer prevention as powerful antioxidants. In this study, the mechanisms of wild pink bayberry free phenolic extract(WPBFE)inhibiting the proliferation and inducing apoptotic of MDA-MB-231 breast cancer cells was examined. The main phenolic acids and flavonols in WPBFE were gallic acid((18.83 ± 0.44)μg/g FW)and myricetin((1.52 ± 0.05)μg/g FW), respectively. The maximum inhibition rate of WPBFE at non-cytotoxicity dose(below 80 mg/mL)was 81%. Western blotting analysis showed that WPBFE could cause the arrest of cell cycle in G0/G1 phase by down-regulating expression levels of PCNA, CDK4, cyclin D1 and up-regulating the expression level of p21. Meanwhile, WPBFE induced apoptosis through initiating the mitochondrial death pathway by up-regulating cleaved caspase-3 and enhancing the ratio of Bax/Bcl-2, with the maximum expression levels of 1.29 and 2.03 folds that of control group, respectively. Further study of the upstream protein, we found that WPBFE down-regulated TRAF2, while upregulated p-ASK1, p-p38 and p-p53. Furthermore, WPBFE could down-regulate the expression of p-PI3K and p-Akt. These observations indicated that WPBFE might play an anticancer role through regulating the p38 MAPK together with PI3K/Akt pathway.展开更多
Neurodegenerative diseases are caused by the progressive loss of specific neurons.The exact mechanisms of action of these diseases are unknown,and many studies have focused on pathways related to abnormal accumulation...Neurodegenerative diseases are caused by the progressive loss of specific neurons.The exact mechanisms of action of these diseases are unknown,and many studies have focused on pathways related to abnormal accumulation and processing of proteins,mitochondrial dysfunction,and oxidative stress leading to apoptotic death.However,a growing body of evidence indicates that aberrant cell cycle re-entry plays a major role in the pathogenesis of neurodegeneration.The activation of the cell cycle in mature neurons could be promoted by several signaling mechanisms,including c-Jun N-terminal kinases,p38 mitogen-activated protein kinases,and mitogen-activated protein kinase/extracellular signal-regulated kinase cascades;post-translational modifications such as Tau-phosphorylation;and DNA damage response.In all these events,implicated Cdk5,a proline-directed serine/threonine protein kinase,seems to be responsible for several cellular processes in neurons including axon growth,neurotransmission,synaptic plasticity,neuronal migration,and maintenance of neuronal survival.However,under pathological conditions,Cdk5 dysregulation may lead to cell cycle re-entry in post-mitotic neurons.Thus,Cdk5 hyperactivation,by its physiologic activator p25,hyper-phosphorylates downstream substrates related to neurodegenerative diseases.This review summarizes factors such as oxidative stress,DNA damage response,signaling pathway disturbance,and Ubiquitin proteasome malfunction contributing to cell cycle re-entry in post-mitotic neurons.It also describes how all these factors are linked to a greater or lesser extent with Cdk5.Thus,it offers a global vision of the function of cell cycle-related proteins in mature neurons with a focus on Cdk5 and how this protein contributes to the development of Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease by cell cycle activation.展开更多
The use of carbon dioxide as a working fluid has been the subject of extensive studies in recent years, particularly in the field of refrigeration where it is at the heart of research to replace CFC and HCFC. Its ther...The use of carbon dioxide as a working fluid has been the subject of extensive studies in recent years, particularly in the field of refrigeration where it is at the heart of research to replace CFC and HCFC. Its thermodynamic properties make it a fluid of choice in the efficient use of energy at low and medium temperatures in engine cycles. However, the performance of transcritical CO2 cycles weakens under high temperature and pressure conditions, especially in refrigeration systems;On the other hand, this disadvantage becomes rather interesting in engine cycles where CO2 can be used as an alternative to the organic working fluid in small and medium-sized electrical systems for low quality or waste heat sources. In order to improve the performance of systems operating with CO2 in the field of refrigeration and electricity production, research has made it possible to develop several concepts, of which this article deals with a review of the state of the art, followed by analyzes in-depth and critical of the various developments to the most recent modifications in these fields. Detailed discussions on the performance and technical characteristics of the different evolutions are also highlighted as well as the factors affecting the overall performance of the systems studied. Finally, perspectives on the future development of the use of CO2 in these different cycles are presented.展开更多
The pursuit of high-energy cathode materials has been focused on raising the charging cutoff voltage of nickel (Ni)-rich layered oxide cathode such as LiNi_(0.8)Co_(0.1)Mn_(0.1)O2 (NCM811). However, the NCM811 suffers...The pursuit of high-energy cathode materials has been focused on raising the charging cutoff voltage of nickel (Ni)-rich layered oxide cathode such as LiNi_(0.8)Co_(0.1)Mn_(0.1)O2 (NCM811). However, the NCM811 suffers from rapid capacity fading upon cycling at cutoff voltage higher than 4.5 V, owing to their structural degradation and labile surface reactivity. Surface-coating with solid electrolytes has been recognized as an effective method to mitigate the performance failure of NCM811 at high voltage. Herein, the nano-sized Li_(6.4)La_(3)Ta_(0.6)Zr_(1.4)O_(12) (LLZTO) is uniformly coated on the surface of single-crystal NCM811 particles, accompanied with the long-range Ta^(5+) diffusion into the transition metal layer of NCM811 lattice. It is revealed that the LLZTO coating can not only inhibit the surface reactions of NCM811 with liquid electrolytes but also play an important role in suppressing the bulk microcracking within the NCM811 particles. The incorporation of Ta^(5+) ion expands the lattice spacing and thereby improves the homogeneity of the Li^(+) diffusion in the single-crystal NCM811, which alleviates the mechanical strain and intragranular cracks caused by nonuniform phases-transformation at high charging voltage. The synergy of surface protection and structural stabilization realized by LLZTO coating enables the NCM811-based lithium batteries to achieve a remarkable electrochemical performance. Typically, LLZTO coated NCM811 delivers a high reversible specific capacity of 202.1 mAh⋅g^(−1) with an excellent capacity retention as high as 70% over 1000 cycles upon charging to 4.5 V at 1 C.展开更多
Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly un...Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.展开更多
BACKGROUND:This study aimed to review bicycle-related injuries during the COVID-19 pandemic to assist with reinforcement or implementation of new policies for injury prevention.METHODS:This is a retrospective descript...BACKGROUND:This study aimed to review bicycle-related injuries during the COVID-19 pandemic to assist with reinforcement or implementation of new policies for injury prevention.METHODS:This is a retrospective descriptive analysis of injuries sustained during cycling for patients 18 years old and above who presented to Singapore General Hospital from January to June 2021.Medical records were reviewed and consolidated.Descriptive analyses were used to summarize patient characteristics,and differences in characteristics subgrouped by triage acuity and discharge status were analyzed.RESULTS:The study included 272 patients with a mean age of 43 years and a male predominance(71.7%).Most presented without referrals(88.2%)and were not conveyed by ambulances(70.6%).Based on acuity category,there were 24(8.8%)Priority 1(P1)patients with 7 trauma activations,174(64.0%)and 74(27.2%)P2 and P3 patients respectively.The most common injuries were fractures(34.2%),followed by superficial abrasion/contusion(29.4%)and laceration/wound(19.1%).Thirteen(4.8%)patients experienced head injury and 85 patients(31.3%)were documented to be wearing a helmet.The majority occurred on the roads as traffic accidents(32.7%).Forty-two patients(15.4%)were admitted with a mean length of stay of 4.1 d and 17(6.3%)undergone surgical procedures.Out of 214(78.7%)discharged patients,no re-attendances or mortality were observed.In the subgroup analysis,higher acuity patients were generally older,with higher proportions of head injuries leading to admission.CONCLUSION:Our study highlights significant morbidities in bicycle-related injuries.There is also a high proportion of fractures in the young healthy male population.Injury prevention is paramount and we propose emphasizing helmet use and road user safety.展开更多
The Internet of Things(IoT)has witnessed a significant surge in adoption,particularly through the utilization of Wireless Sensor Networks(WSNs),which comprise small internet-connected devices.These deployments span va...The Internet of Things(IoT)has witnessed a significant surge in adoption,particularly through the utilization of Wireless Sensor Networks(WSNs),which comprise small internet-connected devices.These deployments span various environments and offer a multitude of benefits.However,the widespread use of battery-powered devices introduces challenges due to their limited hardware resources and communication capabilities.In response to this,the Internet Engineering Task Force(IETF)has developed the IPv6 Routing Protocol for Low-power and Lossy Networks(RPL)to address the unique requirements of such networks.Recognizing the critical role of RPL in maintaining high performance,this paper proposes a novel approach to optimizing power consumption.Specifically,it introduces a developed sensor motes topology integrated with a Radio Duty Cycling(RDC)mechanism aimed at minimizing power usage.Through rigorous analysis,the paper evaluates the power efficiency of this approach through several simulations conducted across different network topologies,including random,linear,tree,and elliptical topologies.Additionally,three distinct RDC mechanisms—CXMAC,ContikiMAC,and NullRDC—are investigated to assess their impact on power consumption.The findings of the study,based on a comprehensive and deep analysis of the simulated results,highlight the efficiency of ContikiMAC in power conservation.This research contributes valuable insights into enhancing the energy efficiency of RPL-based IoT networks,ultimately facilitating their widespread deployment and usability in diverse environments.展开更多
基金supported by the National Natural Science Foundation of China(82173828 and 81874314)the Research Project of the Shanghai Municipal Health Commission(20234Y0082).
文摘Objectives:The pro-oncogenic effects of NCAPD2 have been extensively studied across various tumor types;however,its precise role within the context of lung adenocarcinoma(LUAD)remains elusive.This study aims to elucidate the biological functions of NCAPD2 in LUAD and unravel the underlying mechanistic pathways.Methods:Utilizing bioinformatics methodologies,we explored the differential expression of NCAPD2 between normal and tumor samples,along with its correlations with clinical-pathological characteristics,survival prognosis,and immune infiltration.Results:In the TCGA-LUAD dataset,tumor samples demonstrated significantly elevated levels of NCAPD2 expression compared to normal samples(p<0.001).Clinically,higher NCAPD2 expression was notably associated with advanced T,N,and M stages,pathologic stage,gender,smoking status,and diminished overall survival(OS).Moreover,differentially expressed genes(DEGs)associated with NCAPD2 were predominantly enriched in pathways related to cell division.Immune infiltration analysis revealed that NCAPD2 expression levels were linked to the infiltration of memory B cells,naïve CD4+T cells,activated memory CD4+T cells,and M1 macrophages.In vitro experiments demonstrated that silencing NCAPD2 suppressed LUAD cell proliferation,migration,invasion,epithelial-mesenchymal transition(EMT),and cell cycle progression.Conclusions:In summary,NCAPD2 may represent a promising prognostic biomarker and novel therapeutic target for LUAD.
基金funded by the GRRC Program of Gyeonggi province[GRRC-KyungHee2023(B01)],Republic of Korea.
文摘Objective:To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms.Methods:The effects of Hydrangea serrata extract on growth inhibition of tumor cells and spheroids were assessed using MTT and 3D culture assays.Quantitative real-time PCR and Western blot analyses were employed to investigate the changes in mRNA and protein expression levels of molecules related to cell cycle and apoptosis.Results:Hydrangea serrata extract effectively inhibited the growth of both tumor cells and spheroids.The extract also significantly upregulated p27 mRNA expression and downregulated CDK2 mRNA expression,leading to cell cycle arrest.Moreover,increased BAX/Bcl-2 ratio as well as caspase-9 and-3 were observed after treatment with Hydrangea serrata extract,indicating the induction of tumor cell apoptosis.Conclusions:Hydrangea serrata extract has the potential to alleviate tumors by effectively modulating cell-cycle-related gene expressions and inducing apoptosis,thereby inhibiting tumor growth.
文摘Objective Endometrial carcinoma(EC)is a prevalent gynecological malignancy characterized by increasing incidence and mortality rates.This underscores the critical need for novel therapeutic targets.One such potential target is cell division cycle 20(CDC20),which has been implicated in oncogenesis.This study investigated the effect of the CDC20 inhibitor Apcin on EC and elucidated the underlying mechanism involved.Methods The effects of Apcin on EC cell proliferation,apoptosis,and the cell cycle were evaluated using CCK8 assays and flow cytometry.RNA sequencing(RNA-seq)was subsequently conducted to explore the underlying molecular mechanism,and Western blotting and coimmunoprecipitation were subsequently performed to validate the results.Animal studies were performed to evaluate the antitumor effects in vivo.Bioinformatics analysis was also conducted to identify CDC20 as a potential therapeutic target in EC.Results Treatment with Apcin inhibited proliferation and induced apoptosis in EC cells,resulting in cell cycle arrest.Pathways associated with apoptosis and the cell cycle were activated following treatment with Apcin.Notably,Apcin treatment led to the upregulation of the cell cycle regulator p21,which was verified to interact with CDC20 and consequently decrease the expression of downstream cyclins in EC cells.In vivo experiments confirmed that Apcin treatment significantly impeded tumor growth.Higher CDC20 expression was observed in EC tissue than in nonmalignant tissue,and increased CDC20 expression in EC patients was associated with shorter overall survival and progress free interval.Conclusion CDC20 is a novel molecular target in EC,and Apcin could be developed as a candidate antitumor drug for EC treatment.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2018R1A6A1A03025159).
文摘Krill oil(KO)exhibits various biological activities,such as anti-inflammatory and antitumor effects.However,the inhibitory effects of benign prostatic hyperplasia(BPH)in vitro and in vivo have not yet been studied.This study investigated the anti-BPH effects of KO extracted by an enzymatic hydrolysis method.KO treatment inhibited the proliferation of WMPY-1 and BPH-1 cells by induction of G0/G1 phase arrest through the modulation of positive and negative regulators in both prostate cell types.KO treatment stimulated phosphorylation of c-Jun N-terminal kinase(JNK)and p38 signaling.In addition,KO changed the expression of BPH-related markers(5α-reductase,androgen receptor,FGF,Bcl-2,and Bax)and the activity of the proliferation-mediated NF-κB binding motif.KO-induced levels of proliferation-mediated molecules of prostate cells were attenuated in the presence of siRNA-specific p-38(si-p38)and JNK(si-JNK).Furthermore,the administration of KO alleviated prostate size and weight and the cell layer thickness of prostate glands in a testosterone enanthate-induced BPH rat model.KO treatment altered the level of dihydrotestosterone in serum and the expression levels of BPH-related markers in prostate tissues.Finally,KO-mediated inhibition of prostatic growth was validated by histological analysis.These results suggest that KO has an inhibitory effect on BPH in prostate cells in vitro and in vivo.Thus,KO might be a potential prophylactic or therapeutic agent for patients with BPH.
文摘This study aims to evaluate the effect of serum concentration, synchronization time, and confluence degree on the synchronisation efficiency of goat fibroblast cycle. The results indicated that there was no difference in the percentage of nucleated fibroblasts in the G0/G1 stage between serum concentrations of 0.3% and 0.4% (83.89% and 82.69%, respectively, P > 0.05) as well as between serum concentrations of 0.2% and 0.5% (76.95% and 75.46%, respectively, P > 0.05). The percentage of nucleated fibroblasts in the G0/G1 stage was highest at the concentration of 0.3% and lowest in the control group (83.89% vs. 62.67%, P 0.05). The beneficial effect of high confluence was confirmed by the large percentage of nucleated fibroblasts at the G0/G1 stage. The 60% confluency was significantly lower than the 80% and 100% confluency (73.44%, 86.63%, and 87.17%, respectively, P < 0.05). The results indicate that the goat fibroblast cycle synchronization is the most effective at the serum concentration of 0.3%, 72 hours of synchronization and 100% confluency.
基金This work was supported by the Chinese TMSR Strategic Pioneer Science and Technology Project(No.XDA02010300).
文摘A nonlinear dynamic simulation model based on coordinated control of speed and flow rate for the molten salt reactor and combined cycle systems is proposed here to ensure the coordination and stability between the molten salt reactor and power system.This model considers the impact of thermal properties of fluid variation on accuracy and has been validated with Simulink.This study reveals the capability of the control system to compensate for anomalous situations and maintain shaft stability in the event of perturbations occurring in high-temperature molten salt tank outlet parameters.Meanwhile,the control system’s impact on the system’s dynamic characteristics under molten salt disturbance is also analyzed.The results reveal that after the disturbance occurs,the controlled system benefits from the action of the control,and the overshoot and disturbance amplitude are positively correlated,while the system power and frequency eventually return to the initial values.This simulation model provides a basis for utilizing molten salt reactors for power generation and maintaining grid stability.
基金The authors gratefully acknowledge the financial support of National NaturalScience Foundation of China(Grant No.41972276)Natural Science Foundation of Fujian Province,China(Grant No.2020J06013)"Foal Eagle Program"Youth Top-notch Talent Project of Fujian Province,China(Grant No.00387088).
文摘Enzyme-induced carbonate precipitation(EICP)is an emanating,eco-friendly and potentially sound technique that has presented promise in various geotechnical applications.However,the durability and microscopic characteristics of EICP-treated specimens against the impact of drying-wetting(D-W)cycles is under-explored yet.This study investigates the evolution of mechanical behavior and pore charac-teristics of EICP-treated sea sand subjected to D-W cycles.The uniaxial compressive strength(UCS)tests,synchrotron radiation micro-computed tomography(micro-CT),and three-dimensional(3D)recon-struction of CT images were performed to study the multiscale evolution characteristics of EICP-reinforced sea sand under the effect of D-W cycles.The potential correlations between microstructure characteristics and macro-mechanical property deterioration were investigated using gray relational analysis(GRA).Results showed that the UCS of EICP-treated specimens decreases by 63.7% after 15 D-W cycles.The proportion of mesopores gradually decreases whereas the proportion of macropores in-creases due to the exfoliated calcium carbonate with increasing number of D-W cycles.The micro-structure in EICP-reinforced sea sand was gradually disintegrated,resulting in increasing pore size and development of pore shape from ellipsoidal to columnar and branched.The gray relational degree suggested that the weight loss rate and UCS deterioration were attributed to the development of branched pores with a size of 100-1000 m m under the action of D-W cycles.Overall,the results in this study provide a useful guidancee for the long-term stability and evolution characteristics of EICP-reinforced sea sand under D-W weathering conditions.
基金National Natural Science Foundation of China,Grant/Award Numbers:51972178,52202061Hunan Provincial Nature Science Foundation,Grant/Award Number:2022JJ40068。
文摘Currently,the major challenge in terms of research on K-ion batteries is to ensure that they possess satisfactory cycle stability and specific capacity,especially in terms of the intrinsically sluggish kinetics induced by the large radius of K+ions.Here,we explore high-performance K-ion half/full batteries with high rate capability,high specific capacity,and extremely durable cycle stability based on carbon nanosheets with tailored N dopants,which can alleviate the change of volume,increase electronic conductivity,and enhance the K+ion adsorption.The as-assembled K-ion half-batteries show an excellent rate capability of 468 mA h g^(−1) at 100 mA g^(−1),which is superior to those of most carbon materials reported to date.Moreover,the as-assembled half-cells have an outstanding life span,running 40,000 cycles over 8 months with a specific capacity retention of 100%at a high current density of 2000 mA g^(−1),and the target full cells deliver a high reversible specific capacity of 146 mA h g^(−1) after 2000 cycles over 2 months,with a specific capacity retention of 113%at a high current density of 500 mA g^(−1),both of which are state of the art in the field of K-ion batteries.This study might provide some insights into and potential avenues for exploration of advanced K-ion batteries with durable stability for practical applications.
基金This work was supported of National Natural Science Foundation of China Fund(No.52306033)State Key Laboratory of Engines Fund(No.SKLE-K2022-07)the Jiangxi Provincial Postgraduate Innovation Special Fund(No.YC2022-s513).
文摘The supercritical CO_(2) Brayton cycle is considered a promising energy conversion system for Generation IV reactors for its simple layout,compact structure,and high cycle efficiency.Mathematical models of four Brayton cycle layouts are developed in this study for different reactors to reduce the cost and increase the thermohydraulic performance of nuclear power generation to promote the commercialization of nuclear energy.Parametric analysis,multi-objective optimizations,and four decision-making methods are applied to obtain each Brayton scheme’s optimal thermohydraulic and economic indexes.Results show that for the same design thermal power scale of reactors,the higher the core’s exit temperature,the better the Brayton cycle’s thermo-economic performance.Among the four-cycle layouts,the recompression cycle(RC)has the best overall performance,followed by the simple recuperation cycle(SR)and the intercooling cycle(IC),and the worst is the reheating cycle(RH).However,RH has the lowest total cost of investment(C_(tot))of$1619.85 million,and IC has the lowest levelized cost of energy(LCOE)of 0.012$/(kWh).The nuclear Brayton cycle system’s overall performance has been improved due to optimization.The performance of the molten salt reactor combined with the intercooling cycle(MSR-IC)scheme has the greatest improvement,with the net output power(W_(net)),thermal efficiencyη_(t),and exergy efficiency(η_(e))improved by 8.58%,8.58%,and 11.21%,respectively.The performance of the lead-cooled fast reactor combined with the simple recuperation cycle scheme was optimized to increase C_(tot) by 27.78%.In comparison,the internal rate of return(IRR)increased by only 7.8%,which is not friendly to investors with limited funds.For the nuclear Brayton cycle,the molten salt reactor combined with the recompression cycle scheme should receive priority,and the gas-cooled fast reactor combined with the reheating cycle scheme should be considered carefully.
基金This research was funded by the National Key Research and Development Program of China(2023YFD2301505).
文摘Abscisic acid(ABA),hydrogen peroxide(H_(2)O_(2)) and ascorbate(AsA)–glutathione(GSH)cycle are widely known for their participation in various stresses.However,the relationship between ABA and H_(2)O_(2) levels and the AsA–GSH cycle under drought stress in wheat has not been studied.In this study,a hydroponic experiment was conducted in wheat seedlings subjected to 15%polyethylene glycol(PEG)6000–induced dehydration.Drought stress caused the rapid accumulation of endogenous ABA and H_(2)O_(2) and significantly decreased the number of root tips compared with the control.The application of ABA significantly increased the number of root tips,whereas the application of H_(2)O_(2) markedly reduced the number of root tips,compared with that under 15%PEG-6000.In addition,drought stress markedly increased the DHA,GSH and GSSG levels,but decreased the AsA levels,AsA/DHA and GSH/GSSG ratios compared with those in the control.The activities of the four enzymes in the AsA–GSH cycle were also markedly increased under drought stress,including glutathione reductase(GR),ascorbate peroxidase(APX),monodehydroascorbate reductase(MDHAR)and dehydroascorbate reductase(DHAR),compared with those in the control.However,the application of an ABA inhibitor significantly inhibited GR,DHAR and APX activities,whereas the application of an H_(2)O_(2) inhibitor significantly inhibited DHAR and MDHAR activities.Furthermore,the application of ABA inhibitor significantly promoted the increases of H_(2)O_(2) and the application of H_(2)O_(2) inhibitor significantly blocked the increases of ABA,compared with those under 15% PEG-6000.Taken together,the results indicated that ABA and H_(2)O_(2) probably interact under drought stress in wheat;and both of them can mediate drought stress by modulating the enzymes in AsA–GSH cycle,where ABA acts as the main regulator of GR,DHAR,and APX activities,and H_(2)O_(2) acts as the main regulator of DHAR and MDHAR activities.
基金This work was supported by grants from the National Natural Science Foundation of China(52072005 and 51872279).
文摘Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.
基金supported by the Science and Technology Innovation Program of Hunan Province(Grant Numbers:2021SK1014 and 2022WZ1027)the Colleges and Universities of Hunan Province(Grant Number:HNJG 20200440)+1 种基金the Scientific Research Fund of Hunan Provincial Education Department(Grant Number:21B0411)the Scientific Research Project of Changsha Central Hospital(Number:YNKY202201).
文摘Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.
基金the support from the Guangdong Basic and Applied Basic Research Foundation (2020A1515011376)the National Natural Science Foundation of China (31601397)+2 种基金the Innovative Leading Talents Project of Guangzhou Development ZoneGuangzhou Innovation Leading Talent Projectthe 111 Project (B17018)。
文摘Polyphenol-rich foods have been shown to be good for cancer prevention as powerful antioxidants. In this study, the mechanisms of wild pink bayberry free phenolic extract(WPBFE)inhibiting the proliferation and inducing apoptotic of MDA-MB-231 breast cancer cells was examined. The main phenolic acids and flavonols in WPBFE were gallic acid((18.83 ± 0.44)μg/g FW)and myricetin((1.52 ± 0.05)μg/g FW), respectively. The maximum inhibition rate of WPBFE at non-cytotoxicity dose(below 80 mg/mL)was 81%. Western blotting analysis showed that WPBFE could cause the arrest of cell cycle in G0/G1 phase by down-regulating expression levels of PCNA, CDK4, cyclin D1 and up-regulating the expression level of p21. Meanwhile, WPBFE induced apoptosis through initiating the mitochondrial death pathway by up-regulating cleaved caspase-3 and enhancing the ratio of Bax/Bcl-2, with the maximum expression levels of 1.29 and 2.03 folds that of control group, respectively. Further study of the upstream protein, we found that WPBFE down-regulated TRAF2, while upregulated p-ASK1, p-p38 and p-p53. Furthermore, WPBFE could down-regulate the expression of p-PI3K and p-Akt. These observations indicated that WPBFE might play an anticancer role through regulating the p38 MAPK together with PI3K/Akt pathway.
基金supported by the Spanish Ministry of Industry and Competitiveness[Grant BFU2016-80006-P]The Andalusian Regional Government[Group BIO-216]the FEDER-Andalusian programme 2014-2020[1262530-R].
文摘Neurodegenerative diseases are caused by the progressive loss of specific neurons.The exact mechanisms of action of these diseases are unknown,and many studies have focused on pathways related to abnormal accumulation and processing of proteins,mitochondrial dysfunction,and oxidative stress leading to apoptotic death.However,a growing body of evidence indicates that aberrant cell cycle re-entry plays a major role in the pathogenesis of neurodegeneration.The activation of the cell cycle in mature neurons could be promoted by several signaling mechanisms,including c-Jun N-terminal kinases,p38 mitogen-activated protein kinases,and mitogen-activated protein kinase/extracellular signal-regulated kinase cascades;post-translational modifications such as Tau-phosphorylation;and DNA damage response.In all these events,implicated Cdk5,a proline-directed serine/threonine protein kinase,seems to be responsible for several cellular processes in neurons including axon growth,neurotransmission,synaptic plasticity,neuronal migration,and maintenance of neuronal survival.However,under pathological conditions,Cdk5 dysregulation may lead to cell cycle re-entry in post-mitotic neurons.Thus,Cdk5 hyperactivation,by its physiologic activator p25,hyper-phosphorylates downstream substrates related to neurodegenerative diseases.This review summarizes factors such as oxidative stress,DNA damage response,signaling pathway disturbance,and Ubiquitin proteasome malfunction contributing to cell cycle re-entry in post-mitotic neurons.It also describes how all these factors are linked to a greater or lesser extent with Cdk5.Thus,it offers a global vision of the function of cell cycle-related proteins in mature neurons with a focus on Cdk5 and how this protein contributes to the development of Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral sclerosis,and Huntington’s disease by cell cycle activation.
文摘The use of carbon dioxide as a working fluid has been the subject of extensive studies in recent years, particularly in the field of refrigeration where it is at the heart of research to replace CFC and HCFC. Its thermodynamic properties make it a fluid of choice in the efficient use of energy at low and medium temperatures in engine cycles. However, the performance of transcritical CO2 cycles weakens under high temperature and pressure conditions, especially in refrigeration systems;On the other hand, this disadvantage becomes rather interesting in engine cycles where CO2 can be used as an alternative to the organic working fluid in small and medium-sized electrical systems for low quality or waste heat sources. In order to improve the performance of systems operating with CO2 in the field of refrigeration and electricity production, research has made it possible to develop several concepts, of which this article deals with a review of the state of the art, followed by analyzes in-depth and critical of the various developments to the most recent modifications in these fields. Detailed discussions on the performance and technical characteristics of the different evolutions are also highlighted as well as the factors affecting the overall performance of the systems studied. Finally, perspectives on the future development of the use of CO2 in these different cycles are presented.
基金supported by the National Key R&D Program of China (Grant No.2023YFB2503900)the National Natural Science Foundation of China (Grant No.52372203)Youth Innovation Team of Universities in Shandong Province (Grant No.2023KJ359)。
文摘The pursuit of high-energy cathode materials has been focused on raising the charging cutoff voltage of nickel (Ni)-rich layered oxide cathode such as LiNi_(0.8)Co_(0.1)Mn_(0.1)O2 (NCM811). However, the NCM811 suffers from rapid capacity fading upon cycling at cutoff voltage higher than 4.5 V, owing to their structural degradation and labile surface reactivity. Surface-coating with solid electrolytes has been recognized as an effective method to mitigate the performance failure of NCM811 at high voltage. Herein, the nano-sized Li_(6.4)La_(3)Ta_(0.6)Zr_(1.4)O_(12) (LLZTO) is uniformly coated on the surface of single-crystal NCM811 particles, accompanied with the long-range Ta^(5+) diffusion into the transition metal layer of NCM811 lattice. It is revealed that the LLZTO coating can not only inhibit the surface reactions of NCM811 with liquid electrolytes but also play an important role in suppressing the bulk microcracking within the NCM811 particles. The incorporation of Ta^(5+) ion expands the lattice spacing and thereby improves the homogeneity of the Li^(+) diffusion in the single-crystal NCM811, which alleviates the mechanical strain and intragranular cracks caused by nonuniform phases-transformation at high charging voltage. The synergy of surface protection and structural stabilization realized by LLZTO coating enables the NCM811-based lithium batteries to achieve a remarkable electrochemical performance. Typically, LLZTO coated NCM811 delivers a high reversible specific capacity of 202.1 mAh⋅g^(−1) with an excellent capacity retention as high as 70% over 1000 cycles upon charging to 4.5 V at 1 C.
基金supported by the National Natural Science Foundation of China(82141112)Guangdong Financial Fund for High-Caliber Hospital Construction(174-2018-XMZC-0001-03-0125/D-14)C.W.and the Clinical Research Program of 9th People’s Hospital,Shanghai Jiao Tong University School of Medicine(JYLJ202112).
文摘Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence rate.However,the mechanisms governing tumor initiation and recurrence are poorly understood.Here,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell resolution.Our results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)signatures.Of note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated program.Targeting EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived organoids.These data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.
文摘BACKGROUND:This study aimed to review bicycle-related injuries during the COVID-19 pandemic to assist with reinforcement or implementation of new policies for injury prevention.METHODS:This is a retrospective descriptive analysis of injuries sustained during cycling for patients 18 years old and above who presented to Singapore General Hospital from January to June 2021.Medical records were reviewed and consolidated.Descriptive analyses were used to summarize patient characteristics,and differences in characteristics subgrouped by triage acuity and discharge status were analyzed.RESULTS:The study included 272 patients with a mean age of 43 years and a male predominance(71.7%).Most presented without referrals(88.2%)and were not conveyed by ambulances(70.6%).Based on acuity category,there were 24(8.8%)Priority 1(P1)patients with 7 trauma activations,174(64.0%)and 74(27.2%)P2 and P3 patients respectively.The most common injuries were fractures(34.2%),followed by superficial abrasion/contusion(29.4%)and laceration/wound(19.1%).Thirteen(4.8%)patients experienced head injury and 85 patients(31.3%)were documented to be wearing a helmet.The majority occurred on the roads as traffic accidents(32.7%).Forty-two patients(15.4%)were admitted with a mean length of stay of 4.1 d and 17(6.3%)undergone surgical procedures.Out of 214(78.7%)discharged patients,no re-attendances or mortality were observed.In the subgroup analysis,higher acuity patients were generally older,with higher proportions of head injuries leading to admission.CONCLUSION:Our study highlights significant morbidities in bicycle-related injuries.There is also a high proportion of fractures in the young healthy male population.Injury prevention is paramount and we propose emphasizing helmet use and road user safety.
文摘The Internet of Things(IoT)has witnessed a significant surge in adoption,particularly through the utilization of Wireless Sensor Networks(WSNs),which comprise small internet-connected devices.These deployments span various environments and offer a multitude of benefits.However,the widespread use of battery-powered devices introduces challenges due to their limited hardware resources and communication capabilities.In response to this,the Internet Engineering Task Force(IETF)has developed the IPv6 Routing Protocol for Low-power and Lossy Networks(RPL)to address the unique requirements of such networks.Recognizing the critical role of RPL in maintaining high performance,this paper proposes a novel approach to optimizing power consumption.Specifically,it introduces a developed sensor motes topology integrated with a Radio Duty Cycling(RDC)mechanism aimed at minimizing power usage.Through rigorous analysis,the paper evaluates the power efficiency of this approach through several simulations conducted across different network topologies,including random,linear,tree,and elliptical topologies.Additionally,three distinct RDC mechanisms—CXMAC,ContikiMAC,and NullRDC—are investigated to assess their impact on power consumption.The findings of the study,based on a comprehensive and deep analysis of the simulated results,highlight the efficiency of ContikiMAC in power conservation.This research contributes valuable insights into enhancing the energy efficiency of RPL-based IoT networks,ultimately facilitating their widespread deployment and usability in diverse environments.