The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
Petroleum hydrocarbon pollution is a global concern,particularly in coastal environments.Polycyclic aromatic hydrocarbons(PAHs) are regarded as the most toxic components of petroleum hydrocarbons.In this study,the bio...Petroleum hydrocarbon pollution is a global concern,particularly in coastal environments.Polycyclic aromatic hydrocarbons(PAHs) are regarded as the most toxic components of petroleum hydrocarbons.In this study,the biomonitoring and ranking effects of petroleum hydrocarbons and PAHs on the marine fish model Oryzias melastigma embryos were determined in the Jiulong River Estuary(JRE) and its adjacent waters in China.The results showed that the levels of petroleum hydrocarbons from almost all sites met the primary standard for marine seawater quality,and the concentrations of the 16 priority PAHs in the surface seawater were lower compared with those in other coastal areas worldwide.A new fish expert system based on the embryotoxicity of O.melastigma(OME-FES) was developed and applied in the field to evaluate the biological effects of petroleum hydrocarbons and PAHs.The selected physiological index and molecular indicators in OME-FES were appropriate biomarkers for indicating the harmful effects of petroleum hydrocarbons and PAHs.The outcome of OME-FES revealed that the biological effect levels of the sampling sites ranged from level Ⅰ(no stress) to level Ⅲ(medium stress),which is further corroborated by the findings of nested analysis of variance(ANOVA) models.Our results suggest that the OME-FES is an effective tool for evaluating and ranking the biological effects of marine petroleum hydrocarbons and PAHs.This method may also be applied to evaluate other marine pollutants based on its framework.展开更多
The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.Endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role i...The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.Endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and proteostasis.In this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements.We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases.In summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders.This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.展开更多
There is an increasing interest in biodegradable materials,such as magnesium,for orthopaedic implants.This is driven by their potential to address challenges like stress shielding and the need for secondary removal su...There is an increasing interest in biodegradable materials,such as magnesium,for orthopaedic implants.This is driven by their potential to address challenges like stress shielding and the need for secondary removal surgery.In this study,biodegradable magnesium alloys were produced using the Vacuum Induction Casting technique.The impact of micro-alloying Zn and Ca in Mg-xZn-0.2Ca(x=0.1,0.2,0.3,and 0.4 wt%)alloys on corrosion resistance,cytocompatibility,and early-stage inflammatory response was investigated.XRD and SEM-EDS analysis confirmed the presence of Ca_(2)Mg_(6)Zn_(3)secondary phases in all alloys.The Mg-0.3Zn-0.2Ca alloy exhibited the lowest corrosion rate and an elastic modulus of 36.8 GPa,resembling that of natural bone.Electrochemical measurements indicated a correlation between grain size and secondary phase volume fraction in explaining corrosion behaviour.In vitro degradation in simulated body fluid(SBF)for 21 days showed hydroxyapatite formation on alloy surfaces,aligning with electrochemical studies.In vitro cytotoxicity tests demonstrated the cytocompatibility of all alloys,with Mg-0.3Zn-0.2Ca having the highest cell viability over a 6-day cell culture.Investigation into the inflammatory response with RAW-Blue macrophages revealed the anti-inflammatory properties of Mg-0.3Zn-0.2Ca alloys.Micro-alloying with 0.3 wt%Zn and 0.2 wt%Ca enhanced mechanical properties,corrosion resistance,cytocompatibility,and immunomodulatory properties.This positions the Mg-0.3Zn-0.2Ca alloy as a promising biodegradable implant for bone fixation applications.展开更多
With the increasing penetration of wind and solar energies,the accompanying uncertainty that propagates in the system places higher requirements on the expansion planning of power systems.A source-grid-load-storage co...With the increasing penetration of wind and solar energies,the accompanying uncertainty that propagates in the system places higher requirements on the expansion planning of power systems.A source-grid-load-storage coordinated expansion planning model based on stochastic programming was proposed to suppress the impact of wind and solar energy fluctuations.Multiple types of system components,including demand response service entities,converter stations,DC transmission systems,cascade hydropower stations,and other traditional components,have been extensively modeled.Moreover,energy storage systems are considered to improve the accommodation level of renewable energy and alleviate the influence of intermittence.Demand-response service entities from the load side are used to reduce and move the demand during peak load periods.The uncertainties in wind,solar energy,and loads were simulated using stochastic programming.Finally,the effectiveness of the proposed model is verified through numerical simulations.展开更多
BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascer...BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer sur-gery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients,who received robotic radical gastric cancer surgery.METHODS Initially,an exhaustive retrieval was performed in the PubMed,the Cochrane Library,EMBASE,Web of Science,and Scopus databases to identify relevant studies.Subsequently,a meta-analysis was executed on 6 cohort studies iden-tifying the value of the SIRI in assessing the survival of gastric cancer patients.Additionally,the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators.The association between preoperative SIRI levels and 5-year overall survival(OS)and disease-free survival(DFS)was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer.Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer.SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities,T-stage,carcinoembryonic antigen levels,the development of early serious postoperative complications,and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.展开更多
Offshore wind power is a kind of important clean renewable energy and has attracted increasing attention due to the rapid consumption of non-renewable energy.To reduce the high cost of energy,a possible try is to util...Offshore wind power is a kind of important clean renewable energy and has attracted increasing attention due to the rapid consumption of non-renewable energy.To reduce the high cost of energy,a possible try is to utilize the combination of wind and wave energy considering their natural correlation.A combined concept consisting of a semi-submersible wind turbine and four torus-shaped wave energy converters was proposed and numerically studied under normal operating conditions.However,the dynamic behavior of the integrated system under extreme sea conditions has not been studied yet.In the present work,extreme responses of the integrated system under two different survival modes are evaluated.Fully coupled time-domain simulations with consideration of interactions between the semi-submersible wind turbine and the torus-shaped wave energy converters are performed to investigate dynamic responses of the integrated system,including mooring tensions,tower bending moments,end stop forces,and contact forces at the Column-Torus interface.It is found that the addition of four tori will reduce the mean motions of the yaw,pitch and surge.When the tori are locked at the still water line,the whole integrated system is more suitable for the survival modes.展开更多
For high-speed railways,the smoothness of the railway line significantly affects the operational speed of trains.When the train passes through the turnout on a long-span bridge,the wheel-rail impacts caused by the tur...For high-speed railways,the smoothness of the railway line significantly affects the operational speed of trains.When the train passes through the turnout on a long-span bridge,the wheel-rail impacts caused by the turnout structure irregularities,and the instability arising from the bridge's flexural deformation lead to a strong coupling effect in the vehicle-turnout-bridge system.This significantly affects both ride comfort and operational safety.For addressing this issue,the present study considered a long-span continuous rigid-frame bridge as an example and established a train-turnout-bridge coupled dynamic model of high-speed railway.Utilizing a selfdeveloped dynamic simulation program,the study analysed the dynamic response characteristics when the train passes through the turnouts on the bridge.It also investigated the influence of different span-to-depth ratios of the bridge on the vehicle dynamic response when the train passes through the main line and branch line of turnouts and then proposed a span-to-depth ratio limit value for a long-span continuous rigid-frame bridge.The research findings suggest that the changes in the span-to-depth ratio have a relatively minor impact on the train’s operational performance but significantly affect the dynamic characteristics of the bridge structure.Based on the findings and a comprehensive assessment of safety indicators,it is advisable to establish a span-to-depth ratio limit of 1/4500 for a long-span continuous rigid-frame bridge.展开更多
As an important rice disease, rice bacterial leaf blight (RBLB, caused by the bacterium Xanthomonas oryzae pv.oryzae), has become widespread in east China in recent years. Significant losses in rice yield occurred as ...As an important rice disease, rice bacterial leaf blight (RBLB, caused by the bacterium Xanthomonas oryzae pv.oryzae), has become widespread in east China in recent years. Significant losses in rice yield occurred as a result ofthe disease’s epidemic, making it imperative to monitor RBLB at a large scale. With the development of remotesensing technology, the broad-band sensors equipped with red-edge channels over multiple spatial resolutionsoffer numerous available data for large-scale monitoring of rice diseases. However, RBLB is characterized by rapiddispersal under suitable conditions, making it difficult to track the disease at a regional scale with a single sensorin practice. Therefore, it is necessary to identify or construct features that are effective across different sensors formonitoring RBLB. To achieve this goal, the spectral response of RBLB was first analyzed based on the canopyhyperspectral data. Using the relative spectral response (RSR) functions of four representative satellite or UAVsensors (i.e., Sentinel-2, GF-6, Planet, and Rededge-M) and the hyperspectral data, the corresponding broad-bandspectral data was simulated. According to a thorough band combination and sensitivity analysis, two novel spectralindices for monitoring RBLB that can be effective across multiple sensors (i.e., RBBRI and RBBDI) weredeveloped. An optimal feature set that includes the two novel indices and a classical vegetation index was formed.The capability of such a feature set in monitoring RBLB was assessed via FLDA and SVM algorithms. The resultdemonstrated that both constructed novel indices exhibited high sensitivity to the disease across multiple sensors.Meanwhile, the feature set yielded an overall accuracy above 90% for all sensors, which indicates its cross-sensorgenerality in monitoring RBLB. The outcome of this research permits disease monitoring with different remotesensing data over a large scale.展开更多
This study aims to address the problems existing in the ideological and political education of postgraduate students,and combines the implementation of the mentor responsibility system to explore the role orientation,...This study aims to address the problems existing in the ideological and political education of postgraduate students,and combines the implementation of the mentor responsibility system to explore the role orientation,work content,and practical effects of mentors in the ideological and political education of postgraduate students.Through questionnaire surveys,interviews,and other research methods,the current situation of ideological and political education of postgraduate students under the mentor responsibility system is analyzed,and corresponding optimization strategies are proposed.展开更多
With the increasing demand for information security,traditional single-factor authentication technology can no longer meet security requirements.To this end,this paper proposes a Universal Serial Bus(USB)Key hardware ...With the increasing demand for information security,traditional single-factor authentication technology can no longer meet security requirements.To this end,this paper proposes a Universal Serial Bus(USB)Key hardware and software system based on a two-factor authentication protocol,aiming to improve the security and reliability of authentication.This paper first analyzes the current status and technical principles of USB Key-related research domestically and internationally and designs a two-factor authentication protocol that combines impact/response authentication and static password authentication.The system consists of a host computer and a USB Key device.The host computer interacts with the USB Key through a graphical user interface.The Secure Hash Algorithm 1(SHA-1)and MySQL database are used to implement the authentication function.Experimental results show that the designed two-factor authentication protocol can effectively prevent replay attacks and information tampering,and improve the security of authentication.If the corresponding USB Key is not inserted,the system will prompt that the device is not found.Once the USB Key is inserted,user identity is confirmed through two-factor verification,which includes impact/response authentication and static password authentication.展开更多
Health and Safety issues in the construction industry are of much concern to stakeholders, particularly because of their impact on the industry. This paper explored the roles and responsibilities of stakeholders in en...Health and Safety issues in the construction industry are of much concern to stakeholders, particularly because of their impact on the industry. This paper explored the roles and responsibilities of stakeholders in ensuring health and safety at the construction site. A well-structured interview guide was adopted for the qualitative study. Content analysis was adopted for the analysis of the results. The study revealed that the twelve roles identified by the stakeholders are only limited to the few laws and regulations they are aware of. Whereas the Contractors identified provision of welfare facilities, provision of health and safety policy, and health and safety plan as their key roles, the Consultants’ role was mainly limited to provision of competent site agent and provision of site layout. Abiding by the contractors’ instruction was identified by the Construction Workers as their key responsibilities. The local government officials also identified enforcement of CHS laws and regulations and reporting of incidents to the appropriate authorities, whereas the traditional authorities identified the enforcement of CHS laws and regulations including bye laws and enforcement of customs as their key roles. The findings further show that the stakeholders failed to appreciate some key roles and responsibilities enshrined in CHS laws and regulations in Ghana. The findings contribute to knowledge on stakeholders’ responsibilities in ensuring CHS, and provide valuable reference and insight to practitioners on the roles and responsibilities of the various stakeholders. It is recommended to train and educate stakeholders on all the relevant laws and regulations on CHS in order to improve health and safety at the construction site. The government should also set up a body such as Construction Authority to educate, coordinate, monitor and audit the activities of stakeholders to improve CHS at construction sites.展开更多
By taking Guangzhou City for example,a series of environmental problems brought by agricultural ecological tourism were analyzed from the perspective of environmental degradation caused by that tourism company failed ...By taking Guangzhou City for example,a series of environmental problems brought by agricultural ecological tourism were analyzed from the perspective of environmental degradation caused by that tourism company failed to take environmental responsibility.Based on economic development and environmental protection,some suggestions on environmental protection were proposed from the perspective of perfecting environmental responsibility of tourism company in order to realize win-win of economic development and environmental protection.展开更多
Taking Dongzhai Town in Ningwu County of Shanxi Province as example, this essay explores the spatial structure of towns and villages system from the following perspectives: scale structure, function structure, structu...Taking Dongzhai Town in Ningwu County of Shanxi Province as example, this essay explores the spatial structure of towns and villages system from the following perspectives: scale structure, function structure, structural characteristics of village land-use, and spatial distribution characteristics of Dongzhai villages. There are 5 grades of villages according to their scales, that is, villages have a population over 1 000, between 500 and 1 000, between 100 and 500, less than 100, less than 50. The function structure of Dongzhai Town is divided into 3 grades, Grade 1 (core village), is village with such functions as tourist service, transportation and distribution function. Grade 2 (characteristic village), is agricultural settlement with functions such as industrial function, transportation service, tourist service, and forestry function. Grade 3 (general village), is agricultural settlements with prominent agricultural functions (dry farming). This essay also predicts the change and responses of this town based on the population forecast models. It is predicted that the population of Jiancheng District will reach 4 750 in 2010, 6 400 in 2015, 8 700 in 2020. Returning farmland to forests in Fenhe River valley can ensure the conservation of water resources and the development of tourist service. The proportion of forest land, especially bushes land, and proportion of grassland, especially artificial grass will increase dramatically. The number of slope land will be down a bit. The Lands for settlement and transportation will increase with the development of ecological migration and tourist service. Specialized land such as water area and places of interest will skyrocket. Village patterns and spatial distribution under the system of towns and villages will be improved as well.展开更多
Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack ...Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).展开更多
This study analyzed the impact of land-based contaminants and tertiary industrial structure on economic development in the selected Bohai Bay area,China.Based on panel data spanning 2011-2020,a vector autoregressive(V...This study analyzed the impact of land-based contaminants and tertiary industrial structure on economic development in the selected Bohai Bay area,China.Based on panel data spanning 2011-2020,a vector autoregressive(VAR)model is used to analyze and forecast the short-run and long-run relationships between three industrial structures,pollutant discharge,and economic development.The results showed that the environmental index had a long-term cointegration relationship with the industrial structure economic index.Per capital chemical oxygen demand(PCOD)and per capita ammonia nitrogen(PNH_(3)N)had a positive impact on delta per capita GDP(dPGDP),while per capita solid waste(PSW),the secondary industry rate(SIR)and delta tertiary industry(dTIR)had a negative impact on dPGDP.The VAR model under this coupling system had stability and credibility.The impulse response results showed that the short-term effect of the coupling system on dPGDP was basically consistent with the Granger causality test results.In addition,variance decomposition was used in this study to predict the long-term impact of the coupling system in the next ten periods(i.e.,ten years).It was found that dTIR had a great impact on dPGDP,with a contribution rate as high as 74.35%in the tenth period,followed by the contribution rate of PCOD up to 3.94%,while the long-term contribution rates of PSW,SIR and PNH3N were all less than 1%.The results show that the government should support the development of the tertiary industry to maintain the vitality of economic development and prevent environmental deterioration.展开更多
Data of 44 glacier systems in China used in this paper were obtained from Chinese Glacier Inventories and the meteorological data were got from Meteorological Atlas of Plateau of west China. Based on the statistical a...Data of 44 glacier systems in China used in this paper were obtained from Chinese Glacier Inventories and the meteorological data were got from Meteorological Atlas of Plateau of west China. Based on the statistical analysis and functional model simulation results of the 44 glacier systems in China, the glacier systems were divided into extremely-sensitive glacier system, semi-sensitive glacier system, extremely-steady glacier system and semi-steady glacier system in terms of glacier system's level of water-energy exchange, rising gradient of the equilibrium line altitudes and retreating rate of area to climate warming, their median size and vertical span distribution, and their runoff characteristics to climate warming. Furthermore the functional model of glacier system to climate warming was applied in this paper to predict the average variation trends of the 4 types of glacier systems, which indicate that different sensitivity types of glacier systems respond to the climate warming differently.展开更多
Background: The prognostic nutritional index(PNI) has been widely applied for predicting survival outcomes of patients with various malignant tumors. Although a low PNI predicts poor prognosis in patients with colorec...Background: The prognostic nutritional index(PNI) has been widely applied for predicting survival outcomes of patients with various malignant tumors. Although a low PNI predicts poor prognosis in patients with colorectal cancer after tumor resection, the prognostic value remains unknown in patients with stage Ⅲ colon cancer undergoing curative tumor resection followed by adjuvant chemotherapy. This study aimed to investigate the prognostic value of PNI in patients with stage III colon cancer.Methods: Medical records of 274 consecutive patients with stage Ⅲ colon cancer undergoing curative tumor resection followed by adjuvant chemotherapy with oxaliplatin and capecitabine between December 2007 and December2013 were reviewed. The optimal PNI cutoff value was determined using receiver operating characteristic(ROC) curve analysis. The associations of PNI with systemic inflammatory response markers, including lymphocyte-to-monocyte ratio(LMR), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and C-reactive protein(CRP)level, and clinicopathologic characteristics were assessed using the Chi square or Fisher's exact test. Correlation analysis was performed using Spearman's correlation coefficient. Disease-free survival(DFS) and overall survival(OS)stratified by PNI were analyzed using Kaplan-Meier method and log-rank test, and prognostic factors were identified by Cox regression analyses.Results: The preoperative PNI was positively correlated with LMR(r= 0.483, P < 0.001) and negatively correlated with NLR(r =-0.441, P < 0.001), PLR(r =-0.607, P < 0.001), and CRP level(r =-0.333, P < 0.001). A low PNI(≤49.22)was significantly associated with short OS and DFS in patients with stage ⅢC colon cancer but not in patients with stage ⅢA/ⅢB colon cancer.In addition, patients with a low PNI achieved a longer OS and DFS after being treated with6-8 cycles of adjuvant chemotherapy than did those with < 6 cycles. Multivariate analyses revealed that PNI was independently associated with DFS(hazard ratios 2.001; 95% confidence interval 1.157-3.462; P = 0.013).Conclusion: The present study identified preoperative PNI as a valuable predictor for survival outcomes in patients with stage Ⅲ colon cancer receiving curative tumor resection followed by adjuvant chemotherapy.展开更多
Activity of bc1 complex kinase(ABC1K)is an atypical protein kinase(aPK)that plays a crucial role in plant mitochondrial and plastid stress responses,but little is known about the responses of ABC1Ks to stress in cotto...Activity of bc1 complex kinase(ABC1K)is an atypical protein kinase(aPK)that plays a crucial role in plant mitochondrial and plastid stress responses,but little is known about the responses of ABC1Ks to stress in cotton(Gossypium spp.).Here,we identified 40 ABC1Ks in upland cotton(Gossypium hirsutum L.)and found that the Gh ABC1Ks were unevenly distributed across 17 chromosomes.The GhABC1K family members included 35 paralogous gene pairs and were expanded by segmental duplication.The GhABC1K promoter sequences contained diverse cis-acting regulatory elements relevant to hormone or stress responses.The qRT-PCR results revealed that most Gh ABC1Ks were upregulated by exposure to different stresses.Gh ABC1K2-A05 and Gh ABC1K12-A07 expression levels were upregulated by at least three stress treatments.These genes were further functionally characterized by virus-induced gene silencing(VIGS).Compared with the controls,the Gh ABC1K2-A05-and Gh ABC1K12-A07-silenced cotton lines exhibited higher malondialdehyde(MDA)contents,lower catalase(CAT),peroxidase(POD)and superoxide dismutase(SOD)activities and reduced chlorophyll and soluble sugar contents under NaCl and PEG stress.In addition,the expression levels of six stress marker genes(Gh DREB2A,Gh SOS1,Gh CIPK6,Gh SOS2,Gh WRKY33,and Gh RD29A)were significantly downregulated after stress in the Gh ABC1K2-A05-and Gh ABC1K12-A07-silenced lines.The results indicate that knockdown of Gh ABC1K2-A05 and Gh ABC1K12-A07 make cotton more sensitive to salt and PEG stress.These findings can provide valuable information for intensive studies of Gh ABC1Ks in the responses and resistance of cotton to abiotic stresses.展开更多
BACKGROUND Neoadjuvant chemotherapy(NAC)has become the standard care for advanced adenocarcinoma of esophagogastric junction(AEG),although a part of the patients cannot benefit from NAC.There are no models based on ba...BACKGROUND Neoadjuvant chemotherapy(NAC)has become the standard care for advanced adenocarcinoma of esophagogastric junction(AEG),although a part of the patients cannot benefit from NAC.There are no models based on baseline computed tomography(CT)to predict response of Siewert type II or III AEG to NAC with docetaxel,oxaliplatin and S-1(DOS).AIM To develop a CT-based nomogram to predict response of Siewert type II/III AEG to NAC with DOS.METHODS One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS,and were randomly and consecutively assigned to the training cohort(TC)(n=94)and the validation cohort(VC)(n=34).Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors(version 1.1)criteria.Possible prognostic factors associated with responses after DOS treatment including Siewert classification,gross tumor volume(GTV),and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age.Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS.A nomogram was established based on independent factors to predict the response.The predictive performance of the nomogram was evaluated by Concordance index(C-index),calibration and receiver operating characteristics curve in the TC and VC.RESULTS Univariate analysis showed that Siewert type(52/55 vs 29/39,P=0.005),pretherapeutic cT stage(57/62 vs 24/32,P=0.028),GTV(47.3±27.4 vs 73.2±54.3,P=0.040)were significantly associated with response to DOS in the TC.Multivariate analysis of the TC also showed that the pretherapeutic cT stage,GTV and Siewert type were independent predictive factors related to response to DOS(odds ratio=4.631,1.027 and 7.639,respectively;all P<0.05).The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC(C-index:0.838 and 0.824),with area under the receiver operating characteristic curve of 0.838 and 0.824,respectively.The calibration curves showed that the practical and predicted response to DOS effectively coincided.CONCLUSION A novel nomogram developed with pretherapeutic cT stage,GTV and Siewert type predicted the response of Siewert type II/III AEG to NAC with DOS.展开更多
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
基金The Scientific Research Foundation of the Third Institute of Oceanography,Ministry of Natural Resources under contract Nos 2020014 and 2020017the National Natural Science Foundation of China under contract No.41977211the National Program on Global Change and Air-Sea Interaction under contract No.GASI-02-SCS-YDsum。
文摘Petroleum hydrocarbon pollution is a global concern,particularly in coastal environments.Polycyclic aromatic hydrocarbons(PAHs) are regarded as the most toxic components of petroleum hydrocarbons.In this study,the biomonitoring and ranking effects of petroleum hydrocarbons and PAHs on the marine fish model Oryzias melastigma embryos were determined in the Jiulong River Estuary(JRE) and its adjacent waters in China.The results showed that the levels of petroleum hydrocarbons from almost all sites met the primary standard for marine seawater quality,and the concentrations of the 16 priority PAHs in the surface seawater were lower compared with those in other coastal areas worldwide.A new fish expert system based on the embryotoxicity of O.melastigma(OME-FES) was developed and applied in the field to evaluate the biological effects of petroleum hydrocarbons and PAHs.The selected physiological index and molecular indicators in OME-FES were appropriate biomarkers for indicating the harmful effects of petroleum hydrocarbons and PAHs.The outcome of OME-FES revealed that the biological effect levels of the sampling sites ranged from level Ⅰ(no stress) to level Ⅲ(medium stress),which is further corroborated by the findings of nested analysis of variance(ANOVA) models.Our results suggest that the OME-FES is an effective tool for evaluating and ranking the biological effects of marine petroleum hydrocarbons and PAHs.This method may also be applied to evaluate other marine pollutants based on its framework.
基金supported by the National Natural Science Foundation of China,Nos.92049120 and 81870897STI2030-Major Projects,No.2021ZD0204001+6 种基金Guangdong Key Project for Development of New Tools for the Diagnosis and Treatment of Autism,No.2018B030335001the Natural Science Foundation of Jiangsu Province,No.BK20181436the National Major Scientific and Technological Special Project for Significant New Drug Development,No.2019ZX09301102the Discipline Construction Program of the Second Affiliated Hospital of Soochow University,No.XKTJ-TD202003Sino-German Cooperation Mobility Programme,No.M-0679the Science and Technology Project of Suzhou,No.SKY2022161Research Project of Neurological Diseases of the Second Affiliated Hospital of Soochow University Medical Center,No.ND2023A01(all to QHM)。
文摘The endoplasmic reticulum,a key cellular organelle,regulates a wide variety of cellular activities.Endoplasmic reticulum autophagy,one of the quality control systems of the endoplasmic reticulum,plays a pivotal role in maintaining endoplasmic reticulum homeostasis by controlling endoplasmic reticulum turnover,remodeling,and proteostasis.In this review,we briefly describe the endoplasmic reticulum quality control system,and subsequently focus on the role of endoplasmic reticulum autophagy,emphasizing the spatial and temporal mechanisms underlying the regulation of endoplasmic reticulum autophagy according to cellular requirements.We also summarize the evidence relating to how defective or abnormal endoplasmic reticulum autophagy contributes to the pathogenesis of neurodegenerative diseases.In summary,this review highlights the mechanisms associated with the regulation of endoplasmic reticulum autophagy and how they influence the pathophysiology of degenerative nerve disorders.This review would help researchers to understand the roles and regulatory mechanisms of endoplasmic reticulum-phagy in neurodegenerative disorders.
基金funded by European Union’s Horizon 2020 Research and Innovation program and‘Magnesium based Nano Composites for Orthopedic Applications’MAGNACOM,project under the aegis of Programme for Early-Stage Researchers(PEARL,I-Site ULNE under the Marie Sklodowska-Curie grant agreement)supported by University of Lille(France)and Hauts-de-France region.
文摘There is an increasing interest in biodegradable materials,such as magnesium,for orthopaedic implants.This is driven by their potential to address challenges like stress shielding and the need for secondary removal surgery.In this study,biodegradable magnesium alloys were produced using the Vacuum Induction Casting technique.The impact of micro-alloying Zn and Ca in Mg-xZn-0.2Ca(x=0.1,0.2,0.3,and 0.4 wt%)alloys on corrosion resistance,cytocompatibility,and early-stage inflammatory response was investigated.XRD and SEM-EDS analysis confirmed the presence of Ca_(2)Mg_(6)Zn_(3)secondary phases in all alloys.The Mg-0.3Zn-0.2Ca alloy exhibited the lowest corrosion rate and an elastic modulus of 36.8 GPa,resembling that of natural bone.Electrochemical measurements indicated a correlation between grain size and secondary phase volume fraction in explaining corrosion behaviour.In vitro degradation in simulated body fluid(SBF)for 21 days showed hydroxyapatite formation on alloy surfaces,aligning with electrochemical studies.In vitro cytotoxicity tests demonstrated the cytocompatibility of all alloys,with Mg-0.3Zn-0.2Ca having the highest cell viability over a 6-day cell culture.Investigation into the inflammatory response with RAW-Blue macrophages revealed the anti-inflammatory properties of Mg-0.3Zn-0.2Ca alloys.Micro-alloying with 0.3 wt%Zn and 0.2 wt%Ca enhanced mechanical properties,corrosion resistance,cytocompatibility,and immunomodulatory properties.This positions the Mg-0.3Zn-0.2Ca alloy as a promising biodegradable implant for bone fixation applications.
基金supported by Science and Technology Project of SGCC(SGSW0000FZGHBJS2200070)。
文摘With the increasing penetration of wind and solar energies,the accompanying uncertainty that propagates in the system places higher requirements on the expansion planning of power systems.A source-grid-load-storage coordinated expansion planning model based on stochastic programming was proposed to suppress the impact of wind and solar energy fluctuations.Multiple types of system components,including demand response service entities,converter stations,DC transmission systems,cascade hydropower stations,and other traditional components,have been extensively modeled.Moreover,energy storage systems are considered to improve the accommodation level of renewable energy and alleviate the influence of intermittence.Demand-response service entities from the load side are used to reduce and move the demand during peak load periods.The uncertainties in wind,solar energy,and loads were simulated using stochastic programming.Finally,the effectiveness of the proposed model is verified through numerical simulations.
基金Supported by National Natural Science Foundation of China,No.8236110677Natural Science Foundation of Gansu Province,No.18JR2RA033Gansu Da Vinci Robot High-End Diagnosis and Treatment Team Construction Project,National Key Research and Development Program,No.2020RCXM076.
文摘BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer sur-gery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients,who received robotic radical gastric cancer surgery.METHODS Initially,an exhaustive retrieval was performed in the PubMed,the Cochrane Library,EMBASE,Web of Science,and Scopus databases to identify relevant studies.Subsequently,a meta-analysis was executed on 6 cohort studies iden-tifying the value of the SIRI in assessing the survival of gastric cancer patients.Additionally,the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators.The association between preoperative SIRI levels and 5-year overall survival(OS)and disease-free survival(DFS)was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer.Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer.SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities,T-stage,carcinoembryonic antigen levels,the development of early serious postoperative complications,and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.
基金supported by the National Natural Science Foundation of China(Grant Nos.52171289,42176210,and 52201330)the Guangdong Basic and Applied Basic Research Foundation,China(Grant No.2022B1515250005)Innovation Group Project of Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai)(Grant No.311023014).
文摘Offshore wind power is a kind of important clean renewable energy and has attracted increasing attention due to the rapid consumption of non-renewable energy.To reduce the high cost of energy,a possible try is to utilize the combination of wind and wave energy considering their natural correlation.A combined concept consisting of a semi-submersible wind turbine and four torus-shaped wave energy converters was proposed and numerically studied under normal operating conditions.However,the dynamic behavior of the integrated system under extreme sea conditions has not been studied yet.In the present work,extreme responses of the integrated system under two different survival modes are evaluated.Fully coupled time-domain simulations with consideration of interactions between the semi-submersible wind turbine and the torus-shaped wave energy converters are performed to investigate dynamic responses of the integrated system,including mooring tensions,tower bending moments,end stop forces,and contact forces at the Column-Torus interface.It is found that the addition of four tori will reduce the mean motions of the yaw,pitch and surge.When the tori are locked at the still water line,the whole integrated system is more suitable for the survival modes.
基金supported by the National Key R&D Program of China(2022YFB2602900)the 111 Project(B20040)the China Railway Science and Technology Research and Development Program Project(N2023T011-A(JB)).
文摘For high-speed railways,the smoothness of the railway line significantly affects the operational speed of trains.When the train passes through the turnout on a long-span bridge,the wheel-rail impacts caused by the turnout structure irregularities,and the instability arising from the bridge's flexural deformation lead to a strong coupling effect in the vehicle-turnout-bridge system.This significantly affects both ride comfort and operational safety.For addressing this issue,the present study considered a long-span continuous rigid-frame bridge as an example and established a train-turnout-bridge coupled dynamic model of high-speed railway.Utilizing a selfdeveloped dynamic simulation program,the study analysed the dynamic response characteristics when the train passes through the turnouts on the bridge.It also investigated the influence of different span-to-depth ratios of the bridge on the vehicle dynamic response when the train passes through the main line and branch line of turnouts and then proposed a span-to-depth ratio limit value for a long-span continuous rigid-frame bridge.The research findings suggest that the changes in the span-to-depth ratio have a relatively minor impact on the train’s operational performance but significantly affect the dynamic characteristics of the bridge structure.Based on the findings and a comprehensive assessment of safety indicators,it is advisable to establish a span-to-depth ratio limit of 1/4500 for a long-span continuous rigid-frame bridge.
基金the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA28010500)National Natural Science Foundation of China(Grant Nos.42371385,42071420)Zhejiang Provincial Natural Science Foundation of China(Grant No.LTGN23D010002).
文摘As an important rice disease, rice bacterial leaf blight (RBLB, caused by the bacterium Xanthomonas oryzae pv.oryzae), has become widespread in east China in recent years. Significant losses in rice yield occurred as a result ofthe disease’s epidemic, making it imperative to monitor RBLB at a large scale. With the development of remotesensing technology, the broad-band sensors equipped with red-edge channels over multiple spatial resolutionsoffer numerous available data for large-scale monitoring of rice diseases. However, RBLB is characterized by rapiddispersal under suitable conditions, making it difficult to track the disease at a regional scale with a single sensorin practice. Therefore, it is necessary to identify or construct features that are effective across different sensors formonitoring RBLB. To achieve this goal, the spectral response of RBLB was first analyzed based on the canopyhyperspectral data. Using the relative spectral response (RSR) functions of four representative satellite or UAVsensors (i.e., Sentinel-2, GF-6, Planet, and Rededge-M) and the hyperspectral data, the corresponding broad-bandspectral data was simulated. According to a thorough band combination and sensitivity analysis, two novel spectralindices for monitoring RBLB that can be effective across multiple sensors (i.e., RBBRI and RBBDI) weredeveloped. An optimal feature set that includes the two novel indices and a classical vegetation index was formed.The capability of such a feature set in monitoring RBLB was assessed via FLDA and SVM algorithms. The resultdemonstrated that both constructed novel indices exhibited high sensitivity to the disease across multiple sensors.Meanwhile, the feature set yielded an overall accuracy above 90% for all sensors, which indicates its cross-sensorgenerality in monitoring RBLB. The outcome of this research permits disease monitoring with different remotesensing data over a large scale.
基金Chang’an University Graduate Student Ideological and Political Education Innovation Demonstration Pro-ject(No.300103740013)Education Science Research Project of China Association of Transportation Education(No.JT2022YB222)+1 种基金Research Project on Education and Teaching Reform at Chang’an Dublin International College of Transpor-tation at Chang’an University(No.CDIC-JG-200301)Construction Project for Continuous Improvement of National First-Class Courses on Interchangeability and Measurement Technology(No.300103230119)。
文摘This study aims to address the problems existing in the ideological and political education of postgraduate students,and combines the implementation of the mentor responsibility system to explore the role orientation,work content,and practical effects of mentors in the ideological and political education of postgraduate students.Through questionnaire surveys,interviews,and other research methods,the current situation of ideological and political education of postgraduate students under the mentor responsibility system is analyzed,and corresponding optimization strategies are proposed.
基金funded by the College-level Characteristic Teaching Material Project(Project No.20220119Z0221)The College Teaching Incubation Project(Project No.20220120Z0220)+3 种基金The Ministry of Education Industry-University Cooperation Collaborative Education Project(Project No.20220163H0211)The Central Universities Basic Scientific Research Fund(Project No.3282024009,20230051Z0114,and 20230050Z0114)The Beijing Higher Education“Undergraduate Teaching Reform and Innovation Project”(Project No.20220121Z0208 and 202110018002)The College Discipline Construction Project(Project No.20230007Z0452 and 20230010Z0452)。
文摘With the increasing demand for information security,traditional single-factor authentication technology can no longer meet security requirements.To this end,this paper proposes a Universal Serial Bus(USB)Key hardware and software system based on a two-factor authentication protocol,aiming to improve the security and reliability of authentication.This paper first analyzes the current status and technical principles of USB Key-related research domestically and internationally and designs a two-factor authentication protocol that combines impact/response authentication and static password authentication.The system consists of a host computer and a USB Key device.The host computer interacts with the USB Key through a graphical user interface.The Secure Hash Algorithm 1(SHA-1)and MySQL database are used to implement the authentication function.Experimental results show that the designed two-factor authentication protocol can effectively prevent replay attacks and information tampering,and improve the security of authentication.If the corresponding USB Key is not inserted,the system will prompt that the device is not found.Once the USB Key is inserted,user identity is confirmed through two-factor verification,which includes impact/response authentication and static password authentication.
文摘Health and Safety issues in the construction industry are of much concern to stakeholders, particularly because of their impact on the industry. This paper explored the roles and responsibilities of stakeholders in ensuring health and safety at the construction site. A well-structured interview guide was adopted for the qualitative study. Content analysis was adopted for the analysis of the results. The study revealed that the twelve roles identified by the stakeholders are only limited to the few laws and regulations they are aware of. Whereas the Contractors identified provision of welfare facilities, provision of health and safety policy, and health and safety plan as their key roles, the Consultants’ role was mainly limited to provision of competent site agent and provision of site layout. Abiding by the contractors’ instruction was identified by the Construction Workers as their key responsibilities. The local government officials also identified enforcement of CHS laws and regulations and reporting of incidents to the appropriate authorities, whereas the traditional authorities identified the enforcement of CHS laws and regulations including bye laws and enforcement of customs as their key roles. The findings further show that the stakeholders failed to appreciate some key roles and responsibilities enshrined in CHS laws and regulations in Ghana. The findings contribute to knowledge on stakeholders’ responsibilities in ensuring CHS, and provide valuable reference and insight to practitioners on the roles and responsibilities of the various stakeholders. It is recommended to train and educate stakeholders on all the relevant laws and regulations on CHS in order to improve health and safety at the construction site. The government should also set up a body such as Construction Authority to educate, coordinate, monitor and audit the activities of stakeholders to improve CHS at construction sites.
基金Supported by Innovation Fund of Huazhong Agricultural University in 2009( 52204-10027)~~
文摘By taking Guangzhou City for example,a series of environmental problems brought by agricultural ecological tourism were analyzed from the perspective of environmental degradation caused by that tourism company failed to take environmental responsibility.Based on economic development and environmental protection,some suggestions on environmental protection were proposed from the perspective of perfecting environmental responsibility of tourism company in order to realize win-win of economic development and environmental protection.
基金Supported by Soft Science Research Project of Shanxi Province(2008041034-02 )Institutions and Enterprises Entrusted Project(0908045+1 种基金 0908046 0908043)~~
文摘Taking Dongzhai Town in Ningwu County of Shanxi Province as example, this essay explores the spatial structure of towns and villages system from the following perspectives: scale structure, function structure, structural characteristics of village land-use, and spatial distribution characteristics of Dongzhai villages. There are 5 grades of villages according to their scales, that is, villages have a population over 1 000, between 500 and 1 000, between 100 and 500, less than 100, less than 50. The function structure of Dongzhai Town is divided into 3 grades, Grade 1 (core village), is village with such functions as tourist service, transportation and distribution function. Grade 2 (characteristic village), is agricultural settlement with functions such as industrial function, transportation service, tourist service, and forestry function. Grade 3 (general village), is agricultural settlements with prominent agricultural functions (dry farming). This essay also predicts the change and responses of this town based on the population forecast models. It is predicted that the population of Jiancheng District will reach 4 750 in 2010, 6 400 in 2015, 8 700 in 2020. Returning farmland to forests in Fenhe River valley can ensure the conservation of water resources and the development of tourist service. The proportion of forest land, especially bushes land, and proportion of grassland, especially artificial grass will increase dramatically. The number of slope land will be down a bit. The Lands for settlement and transportation will increase with the development of ecological migration and tourist service. Specialized land such as water area and places of interest will skyrocket. Village patterns and spatial distribution under the system of towns and villages will be improved as well.
基金supported by the National Natural Science Foundation of China(81825009,82071505,81901358)the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2021-I2MC&T-B-099,2019-I2M-5–006)+2 种基金the Program of Chinese Institute for Brain Research Beijing(2020-NKX-XM-12)the King’s College London-Peking University Health Science Center Joint Institute for Medical Research(BMU2020KCL001,BMU2019LCKXJ012)the National Key R&D Program of China(2021YFF1201103,2016YFC1307000).
文摘Background:Choosing the appropriate antipsychotic drug(APD)treatment for patients with schizophrenia(SCZ)can be challenging,as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers.Previous studies have indicated the association between treatment response and genetic and epigenetic factors,but no effective biomarkers have been identified.Hence,further research is imperative to enhance precision medicine in SCZ treatment.Methods:Participants with SCZ were recruited from two randomized trials.The discovery cohort was recruited from the CAPOC trial(n=2307)involved 6 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,Quetiapine,Aripiprazole,Ziprasidone,and Haloperidol/Perphenazine(subsequently equally assigned to one or the other)groups.The external validation cohort was recruited from the CAPEC trial(n=1379),which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine,Risperidone,and Aripiprazole groups.Additionally,healthy controls(n=275)from the local community were utilized as a genetic/epigenetic reference.The genetic and epigenetic(DNA methylation)risks of SCZ were assessed using the polygenic risk score(PRS)and polymethylation score,respectively.The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis,methylation quantitative trait loci,colocalization,and promoteranchored chromatin interaction.Machine learning was used to develop a prediction model for treatment response,which was evaluated for accuracy and clinical benefit using the area under curve(AUC)for classification,R^(2) for regression,and decision curve analysis.Results:Six risk genes for SCZ(LINC01795,DDHD2,SBNO1,KCNG2,SEMA7A,and RUFY1)involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response.The developed and externally validated prediction model,which incorporated clinical information,PRS,genetic risk score(GRS),and proxy methylation level(proxyDNAm),demonstrated positive benefits for a wide range of patients receiving different APDs,regardless of sex[discovery cohort:AUC=0.874(95%CI 0.867-0.881),R^(2)=0.478;external validation cohort:AUC=0.851(95%CI 0.841-0.861),R^(2)=0.507].Conclusions:This study presents a promising precision medicine approach to evaluate treatment response,which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ.Trial registration Chinese Clinical Trial Registry(https://www.chictr.org.cn/),18 Aug 2009 retrospectively registered:CAPOC-ChiCTR-RNC-09000521(https://www.chictr.org.cn/showproj.aspx?proj=9014),CAPEC-ChiCTRRNC-09000522(https://www.chictr.org.cn/showproj.aspx?proj=9013).
基金supported by the research funds for Coupling Research on Industrial Upgrade and Environmental Management in the Bohai Rim-Technique,methodology,and Environmental Economic Policies(No.42076221).
文摘This study analyzed the impact of land-based contaminants and tertiary industrial structure on economic development in the selected Bohai Bay area,China.Based on panel data spanning 2011-2020,a vector autoregressive(VAR)model is used to analyze and forecast the short-run and long-run relationships between three industrial structures,pollutant discharge,and economic development.The results showed that the environmental index had a long-term cointegration relationship with the industrial structure economic index.Per capital chemical oxygen demand(PCOD)and per capita ammonia nitrogen(PNH_(3)N)had a positive impact on delta per capita GDP(dPGDP),while per capita solid waste(PSW),the secondary industry rate(SIR)and delta tertiary industry(dTIR)had a negative impact on dPGDP.The VAR model under this coupling system had stability and credibility.The impulse response results showed that the short-term effect of the coupling system on dPGDP was basically consistent with the Granger causality test results.In addition,variance decomposition was used in this study to predict the long-term impact of the coupling system in the next ten periods(i.e.,ten years).It was found that dTIR had a great impact on dPGDP,with a contribution rate as high as 74.35%in the tenth period,followed by the contribution rate of PCOD up to 3.94%,while the long-term contribution rates of PSW,SIR and PNH3N were all less than 1%.The results show that the government should support the development of the tertiary industry to maintain the vitality of economic development and prevent environmental deterioration.
基金Knowledge Innovation Project of the CAS, No.KZCX2-YW-301National Basic S&T Project of the Ministry of Science and Technology of the People's Republic of China,No.2006FY110200National Natural Science Foundation of China,No.4084002
文摘Data of 44 glacier systems in China used in this paper were obtained from Chinese Glacier Inventories and the meteorological data were got from Meteorological Atlas of Plateau of west China. Based on the statistical analysis and functional model simulation results of the 44 glacier systems in China, the glacier systems were divided into extremely-sensitive glacier system, semi-sensitive glacier system, extremely-steady glacier system and semi-steady glacier system in terms of glacier system's level of water-energy exchange, rising gradient of the equilibrium line altitudes and retreating rate of area to climate warming, their median size and vertical span distribution, and their runoff characteristics to climate warming. Furthermore the functional model of glacier system to climate warming was applied in this paper to predict the average variation trends of the 4 types of glacier systems, which indicate that different sensitivity types of glacier systems respond to the climate warming differently.
基金funded by the National Natural Science Foundation of China(No.81772595,81502459)Sun Yat-sen University Clinical Research 5010 Program(No.2015024,2013013)Science and Technology Planning Project of Guangdong Province(No.2013B021800146)
文摘Background: The prognostic nutritional index(PNI) has been widely applied for predicting survival outcomes of patients with various malignant tumors. Although a low PNI predicts poor prognosis in patients with colorectal cancer after tumor resection, the prognostic value remains unknown in patients with stage Ⅲ colon cancer undergoing curative tumor resection followed by adjuvant chemotherapy. This study aimed to investigate the prognostic value of PNI in patients with stage III colon cancer.Methods: Medical records of 274 consecutive patients with stage Ⅲ colon cancer undergoing curative tumor resection followed by adjuvant chemotherapy with oxaliplatin and capecitabine between December 2007 and December2013 were reviewed. The optimal PNI cutoff value was determined using receiver operating characteristic(ROC) curve analysis. The associations of PNI with systemic inflammatory response markers, including lymphocyte-to-monocyte ratio(LMR), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and C-reactive protein(CRP)level, and clinicopathologic characteristics were assessed using the Chi square or Fisher's exact test. Correlation analysis was performed using Spearman's correlation coefficient. Disease-free survival(DFS) and overall survival(OS)stratified by PNI were analyzed using Kaplan-Meier method and log-rank test, and prognostic factors were identified by Cox regression analyses.Results: The preoperative PNI was positively correlated with LMR(r= 0.483, P < 0.001) and negatively correlated with NLR(r =-0.441, P < 0.001), PLR(r =-0.607, P < 0.001), and CRP level(r =-0.333, P < 0.001). A low PNI(≤49.22)was significantly associated with short OS and DFS in patients with stage ⅢC colon cancer but not in patients with stage ⅢA/ⅢB colon cancer.In addition, patients with a low PNI achieved a longer OS and DFS after being treated with6-8 cycles of adjuvant chemotherapy than did those with < 6 cycles. Multivariate analyses revealed that PNI was independently associated with DFS(hazard ratios 2.001; 95% confidence interval 1.157-3.462; P = 0.013).Conclusion: The present study identified preoperative PNI as a valuable predictor for survival outcomes in patients with stage Ⅲ colon cancer receiving curative tumor resection followed by adjuvant chemotherapy.
基金supported by the State Key Laboratory of Aridland Crop Science,Gansu Agricultural University,China(GSCS-2019-10)the National Natural Science Foundation of China(31801414 and 32260478)+2 种基金the Gansu Province Science and Technology Program,China(20JR10RA531)the Natural Science Foundation of Xinjiang Uygur Autonomous Region,China(2022D01E103)the Education Technology Innovation Project of Gansu Province,China(2022QB-076)。
文摘Activity of bc1 complex kinase(ABC1K)is an atypical protein kinase(aPK)that plays a crucial role in plant mitochondrial and plastid stress responses,but little is known about the responses of ABC1Ks to stress in cotton(Gossypium spp.).Here,we identified 40 ABC1Ks in upland cotton(Gossypium hirsutum L.)and found that the Gh ABC1Ks were unevenly distributed across 17 chromosomes.The GhABC1K family members included 35 paralogous gene pairs and were expanded by segmental duplication.The GhABC1K promoter sequences contained diverse cis-acting regulatory elements relevant to hormone or stress responses.The qRT-PCR results revealed that most Gh ABC1Ks were upregulated by exposure to different stresses.Gh ABC1K2-A05 and Gh ABC1K12-A07 expression levels were upregulated by at least three stress treatments.These genes were further functionally characterized by virus-induced gene silencing(VIGS).Compared with the controls,the Gh ABC1K2-A05-and Gh ABC1K12-A07-silenced cotton lines exhibited higher malondialdehyde(MDA)contents,lower catalase(CAT),peroxidase(POD)and superoxide dismutase(SOD)activities and reduced chlorophyll and soluble sugar contents under NaCl and PEG stress.In addition,the expression levels of six stress marker genes(Gh DREB2A,Gh SOS1,Gh CIPK6,Gh SOS2,Gh WRKY33,and Gh RD29A)were significantly downregulated after stress in the Gh ABC1K2-A05-and Gh ABC1K12-A07-silenced lines.The results indicate that knockdown of Gh ABC1K2-A05 and Gh ABC1K12-A07 make cotton more sensitive to salt and PEG stress.These findings can provide valuable information for intensive studies of Gh ABC1Ks in the responses and resistance of cotton to abiotic stresses.
文摘BACKGROUND Neoadjuvant chemotherapy(NAC)has become the standard care for advanced adenocarcinoma of esophagogastric junction(AEG),although a part of the patients cannot benefit from NAC.There are no models based on baseline computed tomography(CT)to predict response of Siewert type II or III AEG to NAC with docetaxel,oxaliplatin and S-1(DOS).AIM To develop a CT-based nomogram to predict response of Siewert type II/III AEG to NAC with DOS.METHODS One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS,and were randomly and consecutively assigned to the training cohort(TC)(n=94)and the validation cohort(VC)(n=34).Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors(version 1.1)criteria.Possible prognostic factors associated with responses after DOS treatment including Siewert classification,gross tumor volume(GTV),and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age.Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS.A nomogram was established based on independent factors to predict the response.The predictive performance of the nomogram was evaluated by Concordance index(C-index),calibration and receiver operating characteristics curve in the TC and VC.RESULTS Univariate analysis showed that Siewert type(52/55 vs 29/39,P=0.005),pretherapeutic cT stage(57/62 vs 24/32,P=0.028),GTV(47.3±27.4 vs 73.2±54.3,P=0.040)were significantly associated with response to DOS in the TC.Multivariate analysis of the TC also showed that the pretherapeutic cT stage,GTV and Siewert type were independent predictive factors related to response to DOS(odds ratio=4.631,1.027 and 7.639,respectively;all P<0.05).The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC(C-index:0.838 and 0.824),with area under the receiver operating characteristic curve of 0.838 and 0.824,respectively.The calibration curves showed that the practical and predicted response to DOS effectively coincided.CONCLUSION A novel nomogram developed with pretherapeutic cT stage,GTV and Siewert type predicted the response of Siewert type II/III AEG to NAC with DOS.