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Haizhe Jin,1 Meng Xiao,2 Zibo Gong,3 Yinan Zhao4 1Department of Industrial Engineering, School of Business Administration, Northeastern University, Shenyang, People’s Republic of China; 2School of Business Administration, Northeastern University, Shenyang, People’s Republic of China; 3Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China; 4Department of Neurology, The First Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Zibo Gong, Department of Radiology, Shengjing Hospital of China Medical University, No. 36, Sanhao Street, Heping District, Shenyang, People’s Republic of China, Email gongzibomed@163.com Yinan Zhao, Department of Neurology, The First Hospital of China Medical University, Shenyang, People’s Republic of China, Email zhaoyinan1616@yahoo.co.jpBackground: COVID-19 has brought greater workload pressures to the medical field, such as medical staff being required to wear personal protective equipment (PPE). While PPE can protect the safety of staff during the pandemic, it can also accelerate the accumulation of fatigue among operators.Objective: This study explores the influence of different protection states on the mental fatigue of nurses.Methods: In this study, 10 participants (5 males and 5 females) were randomly selected among applicants to monitor mental fatigue during the nurses’ daily work in four different PPE states (low temperature and low protection; low temperature and high protection; high temperature and low protection; high temperature and high protection). The NASA subjective mental fatigue scale was used for subjective evaluation. Reaction time, attention concentration, attention distribution, memory, and main task completion time were used for objective evaluation.Results: The results demonstrated a significant difference in the effects of different protection states on mental fatigue. The state of high temperature and high protection had the greatest influence on mental fatigue, the state of low temperature and low protection had the least, and states of high (low) temperature and low (high) protection had intermediate effects on mental fatigue. Furthermore, the correlation between the subjective and objective fatigue indices was analyzed using a multiple regression model.Conclusion: This study clarified the influence of different protection states on the mental fatigue of nurses, and verified that nurses require more time and energy to complete the same work as before under high protection states. It provides a basis for evaluating the mental fatigue of nurses in the unique period of the COVID-19 pandemic and specific ideas for optimizing the nursing process.Keywords: COVID-19, personal protective equipment, mental fatigue, experimental research, nurse

Cerebral cavernous malformations (CCMs) are angiographically occult cerebrovascular malformations (AOVM) of the central nervous system. They are composed of a sponge-like abnormal vascular mass with numerous thin-walled vessels. CCM incidence rate is approximately 7% of cerebrovascular malformations. The clinical manifestations mainly include seizures, bleeding, headache, etc., with seizures being the most common first symptom, and some patients may be without clinical manifestations. MRI has been the specific diagnostic method for CCMs. This article reports the case of a patient initially diagnosed with multiple myeloma in the left temporal lobe at our hospital in September 2020. Later, the patient was confirmed to have CCMs through surgery and pathology. The main symptom was a sudden onset of cognitive dysfunction, and the patient was discharged after receiving symptomatic and surgical interventions.

China has made great progress in the electrification of passenger cars, and the sales of battery electric vehicles (BEVs) have exceeded 10%. We applied a life-cycle assessment (LCA) method to estimate the carbon dioxide (CO2) emissions of the past (2015), present (2020), and future (2030) BEVs, incorporating China's carbon peaking and neutrality policies, which would substantially reduce emissions from the electricity, operation efficiency, metallurgy, and battery manufacturing industries. BEVs can reduce cradle-to-grave (C2G) CO2 emissions by ∼40% compared with internal combustion engine vehicles (ICEVs) on the national-average level in 2020, far more significant than the benefit in 2015. Improved BEV operating efficiency was the largest factor driving emission reductions from 2015 to 2020. Looking forward to 2030, China's BEVs equipped with nickel–cobalt–manganese (NCM) batteries can achieve a further 43% of CO2 emissions reductions, among which 51 g km−1 of reduction is from the well-to-wheels (WTW) stage majorly owing to the further cleaner electricity mix, while other vehicle-cycle benefits are mainly from the advancement of battery (12 g km−1) and related metal materials (5 g km−1). We highlight the importance of better material efficiency and synchronized decarbonization through the automotive industrial chain in promoting climate mitigation from transport activities.

Although many chemotherapy prodrugs have been developed for tumor therapy, non-targeted delivery, uncontrolled release and tedious construction procedure of prodrugs still limit their clinical application in tumor treatment. In this work, hyaluronic acid (HA) which has tumor-targeting ability was used to conjugate to antitumor drug podophyllotoxin (PPT) to construct a pH-sensitive prodrug named HA-CO-O-PPT just via a one-step esterification reaction. The HA-CO-O-PPT spontaneously assembled into nano spherical micelles in aqueous medium, which had outstanding serum stability and blood compatibility. The obtained prodrug micelles (named HP micelles) exhibited a pH-responsive drug release mode with cumulative release reaching 81.2% due to their dissociation in response to acid stimulus, and had a high cellular uptake efficiency beyond 97% owing to HA receptor-mediated targeting. Furthermore, it was found that the prodrug micelles showed excellent antitumor activities in vivo with the tumor inhibition ratio up to 85% and negligible systemic toxicity. Accordingly, the pH-responsive HP micelles constructed by a simple one-step reaction, could be a promising candidate as a chemotherapeutic agent for cancer therapy.

Background: A hallmark signature of the tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) is abundantly infiltration of cancer-associated fibroblasts (CAFs), which facilitate HNSCC progression. However, some clinical trials showed targeted CAFs ended in failure, even accelerated cancer progression. Therefore, comprehensive exploration of CAFs should solve the shortcoming and facilitate the CAFs targeted therapies for HNSCC.Methods: In this study, we identified two CAFs gene expression patterns and performed the single‐sample gene set enrichment analysis (ssGSEA) to quantify the expression and construct score system. We used multi-methods to reveal the potential mechanisms of CAFs carcinogenesis progression. Finally, we integrated 10 machine learning algorithms and 107 algorithm combinations to construct most accurate and stable risk model. The machine learning algorithms contained random survival forest (RSF), elastic network (Enet), Lasso, Ridge, stepwise Cox, CoxBoost, partial least squares regression for Cox (plsRcox), supervised principal components (SuperPC), generalised boosted regression modelling (GBM), and survival support vector machine (survival-SVM).Results: There are two clusters present with distinct CAFs genes pattern. Compared to the low CafS group, the high CafS group was associated with significant immunosuppression, poor prognosis, and increased prospect of HPV negative. Patients with high CafS also underwent the abundant enrichment of carcinogenic signaling pathways such as angiogenesis, epithelial mesenchymal transition, and coagulation. The MDK and NAMPT ligand–receptor cellular crosstalk between the cancer associated fibroblasts and other cell clusters may mechanistically cause immune escape. Moreover, the random survival forest prognostic model that was developed from 107 machine learning algorithm combinations could most accurately classify HNSCC patients.Conclusion: We revealed that CAFs would cause the activation of some carcinogenesis pathways such as angiogenesis, epithelial mesenchymal transition, and coagulation and revealed unique possibilities to target glycolysis pathways to enhance CAFs targeted therapy. We developed an unprecedentedly stable and powerful risk score for assessing the prognosis. Our study contributes to the understanding of the CAFs microenvironment complexity in patients with head and neck squamous cell carcinoma and serves as a basis for future in-depth CAFs gene clinical exploration.

Social participation is a key factor in achieving active aging. This study aimed to explore the trajectories and predictors of social participation changes among older adults in China. The data used in this study are from the ongoing national longitudinal study CLHLS. A total of 2492 older adults from the cohort study were included. Group-based trajectory models (GBTM) were used to identify potential heterogeneity in longitudinal changes over time and investigate associations between baseline predictors and trajectories for different cohort members using logistic regression. Four different trajectories of social participation were reported in older adults, namely, stable (8.9%), slow decline (15.7%), lower score with decline (42.2%), and higher score with decline (9.5%). On multivariate analyses, age, years of schooling, pension, mental health, cognitive function, instrumental activities of daily living, and initial social participation scores significantly impact the rate of change in social participation over time. Four trajectories of social participation were identified in the Chinese elderly population. Management of mental health, physical function, and cognitive function appear to be important in maintaining the long-term social participation of older people in the community. Early identification of factors influencing the rapid decline in social participation and timely interventions can maintain or improve social participation levels in older adults.

BackgroundWe developed a novel system for quantifying DNA damage response (DDR) to help diagnose and predict the risk of Alzheimer’s disease (AD).MethodsWe thoroughly estimated the DDR patterns in AD patients Using 179 DDR regulators. Single-cell techniques were conducted to validate the DDR levels and intercellular communications in cognitively impaired patients. The consensus clustering algorithm was utilized to group 167 AD patients into diverse subgroups after a WGCNA approach was employed to discover DDR-related lncRNAs. The distinctions between the categories in terms of clinical characteristics, DDR levels, biological behaviors, and immunological characteristics were evaluated. For the purpose of choosing distinctive lncRNAs associated with DDR, four machine learning algorithms, including LASSO, SVM-RFE, RF, and XGBoost, were utilized. A risk model was established based on the characteristic lncRNAs.ResultsThe progression of AD was highly correlated with DDR levels. Single-cell studies confirmed that DDR activity was lower in cognitively impaired patients and was mainly enriched in T cells and B cells. DDR-related lncRNAs were discovered based on gene expression, and two different heterogeneous subtypes (C1 and C2) were identified. DDR C1 belonged to the non-immune phenotype, while DDR C2 was regarded as the immune phenotype. Based on various machine learning techniques, four distinctive lncRNAs associated with DDR, including FBXO30-DT, TBX2-AS1, ADAMTS9-AS2, and MEG3 were discovered. The 4-lncRNA based riskScore demonstrated acceptable efficacy in the diagnosis of AD and offered significant clinical advantages to AD patients. The riskScore ultimately divided AD patients into low- and high-risk categories. In comparison to the low-risk group, high-risk patients showed lower DDR activity, accompanied by higher levels of immune infiltration and immunological score. The prospective medications for the treatment of AD patients with low and high risk also included arachidonyltrifluoromethane and TTNPB, respectively,ConclusionsIn conclusion, immunological microenvironment and disease progression in AD patients were significantly predicted by DDR-associated genes and lncRNAs. A theoretical underpinning for the individualized treatment of AD patients was provided by the suggested genetic subtypes and risk model based on DDR.

On May 3, 2018, Chongqing Center for Disease Control and Prevention (CQCDC) received a report of 15 persons with numbness of the tongue or limbs and vomiting of unknown etiology; all ill persons had attended an adult birthday luncheon in Bishan District, Chongqing municipality, in southwest China. Initial reports indicated that one person had died. Within 2 hours, CQCDC and Western Chinese Field Epidemiology Training Program staff members launched an investigation that included identification of cases, laboratory testing of drinks, and patient interviews to identify the cause of what appeared to be a poisoning. Among the 15 cases, five persons died. The investigation of this apparent mass intoxication implicated a homemade alcoholic beverage produced from a highly toxic flowering plant in the genus Aconitum used in traditional Chinese medicine. Although the risk of aconite toxicity is known, approximately 5,000 cases of aconite poisoning incidents were reported in China, Germany, Japan, and other countries during 1993-2005; most cases of fatal poisoning occurred in China (1). This event highlights the importance of enforcing and complying with existing regulations regarding sale and purchase of Aconitum species (also known as wolfbane), and of dissemination of critical public health messages.

Circulation planning for electric multiple units (EMUs) is regarded as one of the key operation issues for a high-speed railway transportation system. The EMU circulation plan consists of determining the connections of trains while accomplishing the passengers’ demands. EMUs need regular maintenance at a certain interval of kilometers or minutes for safety reasons. Consequently, the circulation plan must ensure that EMU trains can reach the maintenance depots in time for their required maintenance. This paper proposes a 0-1 integer programming model for the EMU circulation plan with the aim of minimizing the total costs of the mileage losses of the EMUs, which is incurred when they undergo a maintenance check before the corresponding travel mileage reaches the limit of the cycle. Given that the accumulated travel mileage of EMUs is allowed to be 10% above the standard mileage cycle in practice, an ingenious fuzzy maintenance constraint is presented to tackle the mileage cycle constraint with a certain elasticity. The exterior penalty function is employed to deal with the fuzzy constraint and a simulated annealing (SA) heuristic is employed to solve the model. The modeling and solving approach are applied to a practical instance in the context of China’s high-speed railway system. Compared with the average travel mileage of EMU trains using the manual solution, with the SA solution an increase of 293 km was observed. It can be then concluded that the optimization method presented in this paper can effectively improve the quality of the EMU circulation plan.

Low drug delivery efficiency elevates the cost of medication, lowers the therapeutic efficacy, and appears as a leading reason for unmet needs in anticancer therapies. Herein, we report the development of self-assembled podophyllotoxin-loaded lipid bilayer nanoparticles that inhibit the production of programmed cell death ligand 1 in lung cancer cells and promote tumor-specific immune responses, thus offering a strategy for regulating the immunosuppressive microenvironment of tumors. In addition, encapsulation of podophyllotoxin in the nanoparticles reduced its systemic toxicity, enhanced its penetration into tumors, and increased its antitumor efficacy. Systemic injection of the nanoparticles into tumor-bearing mice not only prevented tumor immune escape but also significantly inhibited tumor growth and extended survival. In general, the podophyllotoxin-loaded nanoparticles exhibited both immunological effects and antitumor effects in addition to having better targeting activity and fewer side effects than free podophyllotoxin. We expect our findings to facilitate the development of therapies for lung cancer.

Background: Takayasu arteritis (TAK) is a rare autoimmune vasculitis that predominantly affects the aorta and its major branches, including the coronary arteries. Information is limited regarding sex-specific differences in coronary artery involvement among TAK patients. Objective: To assess the differences in coronary angiographic findings and long-term outcomes between male and female TAK patients with coronary artery involvement. Methods: This retrospective cohort study included 87 TAK patients, grouped by sex, who underwent coronary angiography. General characteristics, clinical features, coronary angiographic findings, and therapeutic strategies were obtained from medical records. Major adverse cardiac events (MACE), including death from any cause, myocardial infarction, repeated coronary artery revascularization, and rehospitalization due to unstable or progressive angina or heart failure occurring during follow-up, were also recorded. Results: A total of 207 coronary lesions with stenosis were found in 87 TAK patients. The prevalence of ostial coronary lesions was lower in men than in women (9.1 vs. 23.9%, p=0.031). We observed less moderate stenosis (6.8 vs. 22.7%, p=0.018) and more severe stenosis or occlusion (70.5 vs. 46.0%, p=0.004) in the coronary lesions of male TAK patients. During the up to 7-year follow- up, death from any cause was greater in men than in women (21.4 vs. 1.5%, p=0.003); no other significant differences in MACE occurrence were observed between sexes. Conclusions: Among TAK patients with coronary artery involvement, males tend to have more serious coronary stenosis and a higher risk for long-term mortality than females.

Background Few studies examining the impact of metabolic syndrome and depressive symptoms on subsequent functional disability are available. Objectives To determine the impact of baseline metabolic syndrome and depressive symptoms on subsequent functional disability. Methods This study used data from the 2011 baseline and 2013, 2015 and 2018 follow-up waves of the China Health and Retirement Longitudinal Study (CHARLS). Functional status was assessed by activities of daily living (ADLs) and instrumental ADLs (IADLs). Analyses were restricted to middle-aged and older adults (≥50 years) free of functional disability at baseline. Metabolic syndrome, depressive symptoms, and covariates were measured at baseline. New-onset ADL and IADL disability were obtained in follow-up measurements. Competitive risks based on survival analysis were conducted to examine the impact of baseline metabolic syndrome and depressive symptoms on subsequent functional disability after covariates were controlled. Results Baseline depressive symptoms significantly predicted functional disability over a 7-year follow-up after adjusting for covariates (Hazard ratio [HR] = 1.54, 95% confidence intervals [CI] = 1.40–1.70 for ADL disability; HR=1.36, 95% CI=1.25–1.48 for IADL disability). Metabolic syndrome significantly predicted ADL disability (HR=1.25, 95% CI=1.14–1.38) but not IADL disability (HR=1.02, 95% CI=0.94–1.10). No significant additive interaction between metabolic syndrome and depressive symptoms on functional disability was found. Conclusion The current study found that baseline depressive symptoms were significantly associated with both ADL and IADL disabilities, while metabolic syndrome significantly predicted ADL disability. In addition, some indications showed that the effect in those with both conditions was greater than the sum of the effects separately.

A multifunctional ionic hydrogel with high thermopower, sensitive fire warning, excellent flame retardancy and strain-sensing performance.

Background Urinary incontinence is an increasingly common problem, especially among older people in nursing homes. Nursing assistants are the leading workforce in nursing homes, and their knowledge and attitudes regarding urinary incontinence have garnered considerable attention in the context of aging in China. However, most previous studies on this issue have focused on registered nurses. This study aimed to explore nursing assistants’ knowledge, attitudes and training needs with regard to urinary incontinence. Methods We conducted a two-part mixed-methods study. After institutional manager approval, we surveyed the knowledge and attitudes of 509 nursing assistants regarding urinary incontinence. We carried out semi-structured interviews with 40 nursing assistants to elicit detailed information on training needs. Results In general, knowledge about urinary incontinence was poor (14.00 ± 4.18), although attitudes were primarily positive (35.51 ± 3.19). Most nursing assistants were very willing to learn more about urinary incontinence (93.9%, 478/509), but time constraints and low educational background may be barriers to learning motivation. The three preferred training styles among nursing assistants were face-to-face guidance from a mentor, training combining theory with practice, and online video training. Conclusions Chinese nursing assistants had poor knowledge but positive attitudes toward urinary incontinence. Facility managers should focus on developing training and learning mechanisms regarding urinary incontinence. It is important to adopt diverse training styles according to the actual situation of nursing homes.

We report discoveries of 165 new quasar Ca II absorbers from the Sloan Digital Sky Survey (SDSS) Data Release 7 and 12. Our Ca II rest frame equivalent width distribution supports the weak and strong subpopulations, split at ${W}^{\lambda3934}_{0}=0.7${\AA}. Comparison of both populations' dust depletion shows clear consistency for weak absorber association with halo-type gas in the Milky Way (MW) while strong absorbers have environments consistent with halo and disc-type gas. We probed our high redshift Ca II absorbers for 2175{\AA} dust bumps, discovering 12 2175{\AA} dust absorbers (2DAs). This clearly shows that some Ca II absorbers follow the Large Magellanic Cloud (LMC) extinction law rather than the Small Magellanic Cloud extinction law. About 33% of our strong Ca II absorbers exhibit the 2175{\AA} dust bump while only 6% of weak Ca II absorbers show this bump. 2DA detection further supports the theory that strong Ca II absorbers are associated with disk components and are dustier than the weak population. Comparing average Ca II absorber dust depletion patterns to that of Damped Ly{\alpha} Absorbers (DLAs), Mg II absorbers, and 2DAs shows that Ca II absorbers generally have environments with more dust than DLAs and Mg II absorbers, but less dust than 2DAs. Comparing 2175{\AA} dust bump strengths from different samples and also the MW and LMC, the bump strength appears to grow stronger as the redshift decreases, indicating dust growth and the global chemical enrichment of galaxies in the universe over time., Comment: 17 pages, 24 figures, 5 tables; Acccepted for publication in the Monthly Notices of the Royal Astronomical Society (MNRAS)

Purpose Perivascular epicardial fat stranding detected in the coronary CT angiography was associated with culprit lesion and provided helpful information of risk for ACS. This study aimed to evaluate the potential clinical significance of pericarotid fat stranding (PCFS) and investigate the association between PCFS and short-term prognosis of acute stroke with head and neck CT angiography (CTA). Methods This study included 80 patients (mean age 69.69士11.03; 58 men) who underwent both head and neck CTA and magnetic resonance imaging (MRI) within 2 weeks. Baseline characteristics, PCAT attenuation, plaque characteristics, ischemic penumbra, infarct core volume, infarct core growth rate (CGR) and grade of collateral status between PCFS group and non-PCFS group were recorded, these data were compared by using two-sample t,Mann-Whitney U,Fisher tests and Spearman’s correlation test. Results We found that patients with PCFS had a significantly higher PCAT density than non-PCFS patients (-55.75 ± 5.53 vs -65.82 ± 9.65;P

Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancer, the third leading cause of cancer-associated death worldwide. With the increasing prevalence of metabolic conditions, non-alcoholic fatty liver disease (NAFLD) is emerging as the fastest-growing HCC risk factor, and it imposes an additional layer of difficulty in HCC management. Dysregulated hepatic lipids are generally believed to constitute a deleterious environment cultivating the development of NAFLD-associated HCC. However, exactly which lipids or lipid regulators drive this process remains elusive. We report herein that sphingosine kinase 2 (SphK2), a key sphingolipid metabolic enzyme, plays a critical role in NAFLD-associated HCC. Ablation of Sphk2 suppressed HCC development in NAFLD livers via inhibition of hepatocyte proliferation both in vivo and in vitro. Mechanistically, SphK2 deficiency led to downregulation of ceramide transfer protein (CERT) that, in turn, decreased the ratio of pro-cancer sphingomyelin (SM) to anti-cancer ceramide. Overexpression of CERT restored hepatocyte proliferation, colony growth and cell cycle progression. In conclusion, the current study demonstrates that SphK2 is an essential lipid regulator in NAFLD-associated HCC, providing experimental evidence to support clinical trials of SphK2 inhibitors as systemic therapies against HCC.

ObjectiveMaintaining and delaying a decline in physical function in older adults is critical for healthy aging. This study aimed to explore trajectories, critical points of the trajectory changes, and predictors among older people in the Chinese community.DesignThis study was one with a longitudinal design performed in China.Setting and participantsThe target population was community-dwelling older adults aged over 65 years. A total of 2,503 older adults from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were included in this study.MethodsPhysical functioning was measured by instrumental activities of daily living (IADL). Population-based trajectory models were used to identify potential heterogeneity in longitudinal changes over 16 years and to investigate associations between baseline predictors and different trajectories for different cohort members using LASSO regression and logistic regression.ResultsFour trajectories of physical function were identified: slow decline (33.0%), poor function and moderate decline (8.1%), rapid decline (23.5%), and stable function (35.4%). Older age, male sex, worse self-reported health status, worse vision status, more chronic diseases, worse cognitive function, and a decreased frequency of leisure activity influenced changes in the trajectory of physical function. Having fewer teeth, stronger depressive symptoms, a lack of exercise, and reduced hearing may increase the rate of decline.Conclusion and implicationsFour trajectories of physical function were identified in the Chinese elderly population. Early prevention or intervention of the determinants of these trajectories can maintain or delay the rate of decline in physical function and improve healthy aging.

Raman spectra of two series of InAs/AlAs short-period superlattices were measured at room temperature to investigate the impact of strain on the phonon modes taking into consideration the confinement effect and interface mode. The evolution of strain in the InAs layer and the AlAs layer was studied in (InAs)2/(AlAs)2superlattices grown at various temperatures (400–550 °C). While the strain existed in the AlAs layer remained almost constant, the strain in the InAs layer varied significantly as the growth temperature increased from 500 to 550 °C. The confinement effect on the optical phonons was analyzed based on results from (InAs)n/(AlAs)ngrown at 450 °C (n = 2, 3, 4, and 5). Additionally, the confinement effect was found to be stronger in shorter periods with higher interface quality. The interface phonon modes were resolved between the longitudinal optical and transverse optical phonon modes, which assist in the rough estimation of the thickness of the layers. The disorder-activated acoustic phonon modes at the low-frequency side were also addressed.

How maternal Ezh1 and Ezh2 function in H3K27 methylation in vivo in pre-implantation embryos and during embryonic development is not clear. Here, we have deleted Ezh1 and Ezh2 alone or simultaneously from mouse oocytes. H3K27me3 was absent in oocytes without Ezh2 alone, while both H3K27me2 and H3K27me3 were absent in Ezh1/Ezh2 (Ezh1/2) double knockout (KO) oocytes. The effects of Ezh1/2 maternal KO were inherited in zygotes and early embryos, in which restoration of H3K27me3 and H3K27me2 was delayed by the loss of Ezh2 alone or of both Ezh1 and Ezh2. However, the ablation of both Ezh1 and Ezh2, but not Ezh1 or Ezh2 alone, led to significantly decreased litter size due to growth retardation post-implantation. Maternal Ezh1/2 deficiency caused compromised H3K27me3 and pluripotent epiblast cells in late blastocysts, followed by defective embryonic development. By using RNA-seq, we examined crucial developmental genes in maternal Ezh1/2 KO embryos and identified 80 putatively imprinted genes. Maternal Ezh1/2-H3K27 methylation is inherited in offspring embryos and has a critical effect on fetal and placental development. Thus, this work sheds light on maternal epigenetic modifications during embryonic development.

Urban stormwater systems consist of structural characteristics including topological structure, pipe capacity, low impact developments and storage tanks, and these characteristics are important in ...

An essential problem encountered in a railway freight transport system is determining the best formation plan on a capacity-constrained physical network. The formation plan is not only the foundation of railway operations, but also the basis of train scheduling, yard and terminal management, and infrastructure resource planning. An integrated optimization of the traffic routing and train formation plan aims at designing a globally optimal train service network to decide: between which pairs of reclassification yards (terminals) should provide a block, the frequencies of the train services, the physical paths of traffic, and the block sequences of shipments. This study proposes a non-linear binary programming model to address the integrated problem to minimize the total costs of accumulation, reclassification, and travel distances while satisfying various practical requirements. An efficient simulated annealing based heuristic solution approach is developed to solve the mathematical model. We use a penalty function method to tackle the capacity constraints and a customized method for the operational requirements. The feasibility of the solving approach is tested using a numerical case study based on the east-west railway channel of China. The computational results of a national-scale example based on the China railway network consisting of 235 nodes indicates that the proposed model and approach can achieve good quality solutions within an acceptable computing time.

IntroductionAlzheimer's disease is the most common dementia with clinical and pathological heterogeneity. Cuproptosis is a recently reported form of cell death, which appears to result in the progression of various diseases. Therefore, our study aimed to explore cuproptosis-related molecular clusters in Alzheimer's disease and construct a prediction model.MethodsBased on the GSE33000 dataset, we analyzed the expression profiles of cuproptosis regulators and immune characteristics in Alzheimer's disease. Using 310 Alzheimer's disease samples, we explored the molecular clusters based on cuproptosis-related genes, along with the related immune cell infiltration. Cluster-specific differentially expressed genes were identified using the WGCNA algorithm. Subsequently, the optimal machine model was chosen by comparing the performance of the random forest model, support vector machine model, generalized linear model, and eXtreme Gradient Boosting. Nomogram, calibration curve, decision curve analysis, and three external datasets were applied for validating the predictive efficiency.ResultsThe dysregulated cuproptosis-related genes and activated immune responses were determined between Alzheimer's disease and non-Alzheimer's disease controls. Two cuproptosis-related molecular clusters were defined in Alzheimer's disease. Analysis of immune infiltration suggested the significant heterogeneity of immunity between distinct clusters. Cluster2 was characterized by elevated immune scores and relatively higher levels of immune infiltration. Functional analysis showed that cluster-specific differentially expressed genes in Cluster2 were closely related to various immune responses. The Random forest machine model presented the best discriminative performance with relatively lower residual and root mean square error, and a higher area under the curve (AUC = 0.9829). A final 5-gene-based random forest model was constructed, exhibiting satisfactory performance in two external validation datasets (AUC = 0.8529 and 0.8333). The nomogram, calibration curve, and decision curve analysis also demonstrated the accuracy to predict Alzheimer's disease subtypes. Further analysis revealed that these five model-related genes were significantly associated with the Aβ-42 levels and β-secretase activity.ConclusionOur study systematically illustrated the complicated relationship between cuproptosis and Alzheimer's disease, and developed a promising prediction model to evaluate the risk of cuproptosis subtypes and the pathological outcome of Alzheimer's disease patients.

Objectives: This study evaluates the cost–effectiveness of adding prolonged-release (PR)-fampridine to best supportive care (BSC) versus BSC alone in adult multiple sclerosis patients with walking disability in China. Materials & methods: A hybrid decision tree and Markov model from both the societal and healthcare perspectives were constructed. Parameters were derived from clinical trials of PR-fampridine, published sources and clinical expert interviews. Results: Over a 10-year time horizon, adding PR-fampridine to BSC led to 0.15 quality-adjusted life year (QALY) gain and lower costs, with incremental cost–effectiveness ratios of -238,806 Chinese Yuan/QALY and -113,488 Chinese Yuan/QALY from the societal and healthcare perspectives, respectively. Conclusion: Compared with BSC alone, PR-fampridine plus BSC is considered an economically dominant strategy for the treatment of multiple sclerosis-related walking disability in China.

Photothermal therapy is a novel strategy for cancer treatment, which can kill tumor cells by converting light energy into heat energy through irradiating photothermal conversion materials with laser. As a common photothermal agent, gold nanorods (GNRs) have characteristics of high conversion efficiency and long circulation time in vivo. However, improving stability and reducing toxicity of GNRs remain a significant challenge. In this research, a simple and novel strategy for the synthesis of modified GNRs was proposed. The polysaccharide CL90 was obtained from lemon, which was modified to afford thiolated lemon polysaccharide (SH-CL90). SH-CL90 was used to prepare stable GNRs and give the composite GNRs-SH-CL90, which was found to have good stability in PBS solution and possess high photothermal conversion effects and photothermal stability. The biological experiments revealed that GNRs-SH-CL90 inhibited tumor cell proliferation under near-infrared light irradiation and could induce apoptosis significantly. Furthermore, in vivo experiments supported that GNRs-SH-CL90 could inhibit the proliferation and migration of tumor cells. All the experiments demonstrated that GNRs-SH-CL90 might be promising in the field of cancer treatment.

Background Screening is often recommended as a first step in frailty management. Many guidelines call to implicate frailty screening into practice in the primary care setting. However, few countries or organizations implement it. Understanding and clarifying the stakeholders’ views and issues faced by the implementation is essential to the successful implementation of frailty screening. However, the systematic review on stakeholders’ views of frailty screening in primary care is decidedly limited. Our objective was to explore the perspective of older adults, caregivers, and healthcare providers on frailty screening and determine the enablers and barriers to implementing frailty screening in primary care. Methods A systematic search of six databases and other resources was conducted following JBI’s three-step search strategy. The search resulted in 7362 articles, of which 97 were identified for further assessment according to the inclusion criteria. After the full-text screening, quality assessment and data extraction were carried out using the tools from Joanna Briggs Institute (JBI). Moreover, reviewers used the approach of meta-aggregative of JBI to analyze data and synthesis the findings. Results Six studies were included. A total of 63 findings were aggregated into 12 categories and then further grouped into three synthesized findings:1) capacity of healthcare providers and older adults; 2) opportunity in the implementation of frailty screening; 3) motivation in the implementation of frailty screening. These themes can help identify what influences the implementation of screening from the perspective of stakeholders. Conclusions This meta-synthesis provides evidence on the barriers and enablers of frailty screening in primary care, from the aspects of psychological, physical, social, material, etc. However, stakeholder perspectives of frailty screening have not been adequately studied. More research and efforts are needed to explore the influencing factors and address the existing barriers.

Because of the complexity of cancer ecosystems, the efficacy of single-agent chemotherapy is limited. Herein, we report the use of cationic nanoparticles (designated PPCNs) generated from a chemically modified form of the chemotherapeutic agent podophyllotoxin (PPT) to deliver both microRNA-424 (miR-424) and PPT to tumor cells, thus combining chemotherapy and gene therapy. We evaluated the optimal loading ratio of miR-424─which targets programmed cell death ligand 1 (PD-L1) mRNA and reduces PD-L1 production, thus promoting the attack of tumor cells by T cells─for effective delivery of miR-424 and PPCNs into nonsmall-cell lung cancer cells (H460). Because miR-424 can reverse chemotherapy resistance, treatment of the tumor cells with the combination of miR-424 and PPT enhanced their sensitivity to PPT. Because miR-424 and the PPCNs regulated PD-L1 production in different ways, the miR-424@PPCN complexes were significantly more efficacious than either miR-424 or PPCNs alone. We also demonstrated that treatment of tumor-bearing mice with these complexes significantly inhibited tumor growth and extended survival. Moreover, additional in vitro experiments revealed that the complexes could remodel the tumor immune microenvironment, relieve immunosuppression, and achieve immune normalization. This novel system for delivering a combination of PPT and miR-424 shows great potential for the multimodal treatment of lung cancer.

Medication administration errors account for a relatively high proportion of medical errors, with more than 50% occurring at the nursing administration stage. Nursing is characterized by a large amount of work, rigid working hours, high information cognitive intensity, and frequent information updates. The high workload of nurses is a significant cause of medication administration errors. In this study, a literature analysis was used to determine the elements of the system dynamics model, and the causal loop diagram was used to draw the relationship framework among the elements. Vensim personal learning edition and interview surveys were then used for model validation and simulation. First, 302 case analyses of medication administration errors collected from the three metropolitan area hospitals were used to construct the causal loop diagram, the stock and flow map of the medication administration error system, and the dynamics model; second, the model was tested from theoretical and historical data simulation perspectives; finally, the system dynamics model proposed in this study was used to simulate a medical institution from overtime and policy perspectives. Through system dynamics modeling, the inducing mechanism of workload on medication administration errors in nursing operations was elucidated, and corresponding suggestions for prevention were provided. In addition, ideas and basis for optimizing the medication administration process, improving workload, and preventing medication administration errors considering workload were provided.