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Abstract Background The National Medical Licensing Examination (NMLE) is the only objective, standardized metric to evaluate whether a medical student possessing the professional knowledge and skills necessary to work as a physician. However, the overall pass rate of NMLE in our hospital in 2021 was much lower than that of Peking Union Medical College Hospital, which was required to be further improved. Methods To find the reasons for the unsatisfactory performance in 2021, the quality improvement team (QIT) organized regular face-to-face meetings for in-depth discussion and questionnaire, and analyzed the data by “Plato analysis” and “Brainstorming method”. After finding out the reasons, the “Plan-Do-Check-Action” (PDCA) cycle was continued to identify and solve problems, which included the formulation and implementation of specific training plans by creating the “Gantt charts”, the check of effects, and continuous improvements from 2021 to 2022. Detailed information about the performance of students in 2021 and 2022, and the attendance, assessment, evaluation and suggestions from our hospital were provided by the relevant departments, and the pass rate-associated data was collected online. Results After the PDCA plan, the pass rate of NMLE in our hospital increased by 10.89% from 80.15% in 2021 to 91.04% in 2022 (P = 0.0109), with the pass rate of skill examination from 95.59% in 2021 to 99.25% in 2022 (P = 0.0581) and theoretical examination from 84.5% in 2021 to 93.13% in 2022 (P = 0.027). Additionally, the mean scores of all examinees increased with the theoretical examination score increasing from 377.0 ± 98.76 in 2021 to 407.6 ± 71.94 in 2022 (P = 0.004). Conclusions Our results showed a success application of the PDCA plan in our hospital which improved the pass rate of the NMLE in 2022, and the PDCA plan may provide a practical framework for future medical education and further improve the pass rate of NMLE in the next year.

In order to further improve the safety of coal mine comprehensive mining operations, a set of coal mine comprehensive mining personnel positioning and hydraulic support system control system is proposed with intelligent technology as the starting point; by designing a precise positioning system, dividing the control area of the coal mining face, and integrating the design system, an intelligent and automated coal mine comprehensive mining face working system was ultimately constructed. The application of collaborative control system in Daliuta Coal Mine shows that the system has strong safety and high stability, and can effectively ensure the life safety of coal mine comprehensive mining face operators.

Abstract Background Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, yet its influence on offspring growth remains unclear. Our study dynamically tracks growth rates in children from ICP and healthy mothers and investigates the link between maternal liver function and developmental abnormalities in offspring. Method Our case‒control study involved 97 women with ICP and 152 with uncomplicated pregnancies nested in a cohort of their offspring, including 50 from the ICP group and 87 from the uncomplicated pregnancy group. We collected pediatric growth and development data, with a maximum follow-up duration of 36 months. Stratified analyses of children's height, weight, and head circumference were conducted, and Spearman's rank correlation was applied to examine the relationships between maternal serological markers and pediatric growth metrics. Result Maternal liver and renal functions, along with serum lipid profiles, significantly differed between the ICP and normal groups. In the ICP group, the offspring showed elevated alanine aminotransferase (ALT), direct bilirubin (DBIT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APOB) levels. Notably, the length-for-age z score (LAZ), weight-for-age z score (WAZ), and head circumference-for-age z score (HCZ) were lower in ICP offspring compared with those from normal pregnancies within the 1- to 12-month age range (P

Abstract Background Colorectal cancer (CRC) is a prevalent malignancy with high mortality and morbidity rates. Although the significant efficacy of immunotherapy is well established, it is only beneficial for a limited number of individuals with CRC. Methods Differentially expressed immune-related genes (DE-IRGs) were retrieved from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and ImmPort databases. A prognostic signature comprising DE-IRGs was developed using univariate, LASSO, and multivariate Cox regression analyses. A nomogram integrating the independent prognostic factors was also developed. CIBERSORT was used to assess immune cell infiltration (ICI). Furthermore, wound-healing, colony formation, migration, and invasion assays were performed to study the involvement of ACTG1 in CRC. Results A signature including six DE-IRGs was developed. The overall survival (OS) rate was accurately estimated for TCGA and GSE38832 cohorts. The risk score (RS) of the signature was an independent factor for OS. Moreover, a nomogram encompassing age, RS, and pathological T stage accurately predicted the long-term OS probability of individuals with CRC. The high-risk group had an elevated proportion of patients treated with ICIs, including native B cells, relative to the low-risk group. Additionally, ACTG1 expression was upregulated, which supported the proliferation, migration, and invasion abilities of CRC cells. Conclusions An immune-related prognostic signature was developed for predicting OS and for determining the immune status of individuals with CRC. The present study provides new insights into accurate immunotherapy for individuals with CRC. Moreover, ACTG1 may serve as a new immune biomarker.

Background: Anal condyloma acuminatum (CA) is marked by its thorny treatment and high recurrence rate. Although 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrates significant efficacy and safety in treating anal CA, it does not completely prevent recurrence. This study aimed to develop and validate a nomogram model in predicting the risk of relapse in HIV-negative patients with anal CA following treatment with ALA-PDT. Methods: A retrospective analysis was conducted on patients diagnosed with anal CA who received combined CO2 laser vaporization and ALA-PDT between January 2013 and May 2023. Patients were divided into recurrence and non-recurrence groups. A nomogram was developed based on factors showing statistical significance in multivariable logistic regression analysis. The discriminative ability and clinical utility of the nomogram were assessed via ROC curves and decision curve analysis, with internal validation performed through bootstrap resampling. Results: Among the 176 patients included, 33 (18.75 %) experienced recurrence, while 143 did not. Independent predictors for recurrence included HPV types, history of anal intercourse, and the number of CO2 laser treatments received. Incorporating these predictors, the nomogram demonstrated a superior diagnostic performance (area under the curve = 0.881, 95 % CI: 0.818–0.935) and a significant net benefit in decision curve analysis. Conclusions: The nomogram accurately predicts the risk of recurrence in HIV-negative patients with anal CA following ALA-PDT. It offers a valuable tool for guiding preoperative clinical decision-making and establishing personalized treatment strategies to minimize the risk of relapse.

Abstract Objective Sepsis-induced coagulopathy (SIC) is extremely common in individuals with sepsis, significantly associated with poor outcomes. This study attempted to develop an interpretable and generalizable machine learning (ML) model for early predicting the risk of 28-day death in patients with SIC. Methods In this retrospective cohort study, we extracted SIC patients from the Medical Information Mart for Intensive Care III (MIMIC-III), MIMIC-IV, and eICU-CRD database according to Toshiaki Iba's scale. And the overlapping in the MIMIC-IV was excluded for this study. Afterward, only the MIMIC-III cohort was randomly divided into the training set, and the internal validation set according to the ratio of 7:3, while the MIMIC-IV and eICU-CRD databases were considered the external validation sets. The predictive factors for 28-day mortality of SIC patients were determined using recursive feature elimination combined with tenfold cross-validation (RFECV). Then, we constructed models using ML algorithms. Multiple metrics were used for evaluation of performance of the models, including the area under the receiver operating characteristic curve (AUROC), area under the precision recall curve (AUPRC), accuracy, sensitivity, specificity, negative predictive value, positive predictive value, recall, and F1 score. Finally, Shapley Additive Explanations (SHAP), Local Interpretable Model-Agnostic Explanations (LIME) were employed to provide a reasonable interpretation for the prediction results. Results A total of 3280, 2798, and 1668 SIC patients were screened from MIMIC-III, MIMIC-IV, and eICU-CRD databases, respectively. Seventeen features were selected to construct ML prediction models. XGBoost had the best performance in predicting the 28-day mortality of SIC patients, with AUC of 0.828, 0.913 and 0.923, the AUPRC of 0.807, 0.796 and 0.921, the accuracy of 0.785, 0.885 and 0.891, the F1 scores were 0.63, 0.69 and 0.70 in MIMIC-III (internal validation set), MIMIC-IV, and eICU-CRD databases. The importance ranking and SHAP analyses showed that initial SOFA score, red blood cell distribution width (RDW), and age were the top three critical features in the XGBoost model. Conclusions We developed an optimal and explainable ML model to predict the risk of 28-day death of SIC patients 28-day death risk. Compared with conventional scoring systems, the XGBoost model performed better. The model established will have the potential to improve the level of clinical practice for SIC patients. Graphical Abstract

The current standard treatment for locally advanced squamous cell carcinoma of the head and neck (LASCCHN) comprises concurrent radiotherapy (CRT) alongside platinum-based chemotherapy. However, innovative therapeutic alternatives are being evaluated in phase II/III randomized trials. This study employed a Bayesian network meta-analysis (NMA) using fixed effects to provide both direct and indirect comparisons of all existing treatment modalities for unresectable LASCCHN. Methods: We referenced randomized controlled trials (RCTs) from January 2000 to July 2023 by extensively reviewing PubMed, EMBASE, and Web of Science databases, adhering to the Cochrane methodology. Relevant data, including summary estimates of overall survival (OS) and progression-free survival (PFS), were extracted from these selected studies and recorded in a predefined database sheet. Subsequently, we conducted a random effects network meta-analysis using a Bayesian framework. Results: Based on the Surface Under the Cumulative Ranking (SUCRA) values, the league table organizes the various treatments for OS in the following order: IC + RT&MTT, MTT-CRT, IC + CRT&MTT, CRT, IC + CRT, MTT-RT, IC + MTT-RT, and RT. In a similar order, the treatments rank as follows according to the league table: IC + CRT&MTT, MTT-CRT, IC + CRT, IC + RT&MTT, CRT, IC + MTT-RT, MTT-RT, and RT. Notably, none of these treatments showed significant advantages over concurrent chemoradiotherapy. Conclusion: Despite concurrent chemoradiotherapy being the prevailing treatment for LASCCHN, our findings suggest the potential for improved outcomes when concurrent chemoradiotherapy is combined with targeted therapy or induction chemotherapy.

Background Bell’s palsy is an idiopathic peripheral nerve palsy involving the facial nerve. Pregnancy, diabetes mellitus and hypertension are the risk factors for Bell’s palsy. However, the association between hypertensive disorders and Bell’s palsy during pregnancy or the puerperium remains unclear. This systematic review will comprehensively summarise the literature and evaluate the association between Bell’s palsy and hypertensive disorders during pregnancy or the puerperium.Methods and analysis Systematic searches of PubMed, MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials will be undertaken using prespecified search strategies. Observational studies (cross-sectional studies, cohort studies, case reports and series case reports) written in English that investigate the association between hypertensive disorders of late pregnancy and Bell’s palsy during pregnancy or the puerperium will be included. Different authors will independently conduct the eligible study selection, perform data extraction and appraise the quality of included studies. Subgroup analysis will be carried out based on the age of pregnant women (≤35 years old, >35 years old), parity (primipara, multipara) and fetus number (singleton or multiple-gestation pregnancy).Ethics and dissemination This review will be based on published literature, and thus there is no requirement for ethics approval. The results of this study will aid in the knowledge of the relationship between Bell’s palsy during pregnancy or the puerperium and hypertensive disorders of late pregnancy. The results of this systematic review will be shared through publication in a peer-reviewed journal with good visibility for the field of obstetrics and presentations at academic conferences.PROSPERO registration number CRD42023422902.

Abstract Background Single-cell multiplex imaging data have provided new insights into disease subtypes and prognoses recently. However, quantitative models that explicitly capture single-cell resolution cell-cell interaction features to predict patient survival at a population scale are currently missing. Methods We quantified hundreds of single-cell resolution cell-cell interaction features through neighborhood calculation, in addition to cellular phenotypes. We applied these features to a neural-network-based Cox-nnet survival model to identify survival-associated features. We used non-negative matrix factorization (NMF) to identify patient survival subtypes. We identified atypical subpopulations of triple-negative breast cancer (TNBC) patients with moderate prognosis and Luminal A patients with poor prognosis and validated these subpopulations by label transferring using the UNION-COM method. Results The neural-network-based Cox-nnet survival model using all cellular phenotype and cell-cell interaction features is highly predictive of patient survival in the test data (Concordance Index > 0.8). We identify seven survival subtypes using the top survival features, presenting distinct profiles of epithelial, immune, and fibroblast cells and their interactions. We reveal atypical subpopulations of TNBC patients with moderate prognosis (marked by GATA3 over-expression) and Luminal A patients with poor prognosis (marked by KRT6 and ACTA2 over-expression and CDH1 under-expression). These atypical subpopulations are validated in TCGA-BRCA and METABRIC datasets. Conclusions This work provides an approach to bridge single-cell level information toward population-level survival prediction.

Most of the existing accurate positioning systems for underground personnel adopt UWB positioning technology, which is based on the layout mode of personnel positioning card + positioning substation to achieve centimeter-level high precision positioning. However, the existing models ignore the complexity of the working face environment, the influence of the change of the location of the base station installed with hydraulic support on the positioning accuracy, as well as the difficulty of field installation and other factors. To solve the above problems, a low power consumption positioning system for fully mechanized mining face is designed, which adopts Bluetooth positioning and LoRa wireless technology. The locator is used as a beacon and powered by battery, which can be installed in any position of the working face. Personnel positioning card integrates Bluetooth positioning and LoRa wireless technology, and integrates with mining lamp to form information mining lamp; the substation fusion LoRa wireless module is installed at both ends of the fully mechanized face to collect and transmit location information. The system can be compatible with the existing personnel accurate positioning system, and avoid the problems that the existing technology is difficult to solve in the positioning of fully mechanized mining face. It has the advantages of convenient installation, low cost and easy maintenance.

Background. While observation studies have shown a positive correlation between inflammatory bowel disease (IBD) and the risk of nonmalignant digestive system diseases, a definitive causal relationship has not yet been clearly established. Methods. Mendelian randomization (MR) was employed to investigate the potential causal association between genetic susceptibility to IBD and nonmalignant gastrointestinal diseases. Genetic variants were extracted as instrumental variables (IVs) from a genome-wide association study (GWAS) meta-analysis, which included 12,194 cases of Crohn’s disease (CD) and 28,072 control cases of European ancestry. The GWAS for ulcerative colitis (UC) included 12,366 UC and 33,609 control cases of European ancestry. All IVs reached genome-wide significance (GWAS p value

Abstract Objective Anlotinib is a multitarget anti-angiogenic drug that combined with temozolomide (TMZ) can effectively prolongs the overall survival (OS) of recurrent malignant glioma(rMG),but some patients do not respond to anlotinib combined with TMZ. These patients were associated with a worse prognosis and lack effective identification methods. Therefore, it is necessary to differentiate patients who may have good response to anlotinb in combination with TMZ from those who are not, in order to provide personalized targeted therapies. Methods Fifty three rMG patients (42 in training cohort and 11 in testing cohort) receiving anlotinib combined with TMZ were enrolled. A total of 3668 radiomics features were extracted from the recurrent MRI images. Radiomics features are reduced and filtered by hypothesis testing and Least Absolute Shrinkage And Selection (LASSO) regression. Eight machine learning models construct the radiomics model, and then screen out the optimal model. The performance of the model was assessed by its discrimination, calibration, and clinical usefulness with validation. Results Fifty three patients with rMG were enrolled in our study. Thirty four patients displayed effective treatment response, showed a higher survival benefits than non-response group, the median progression-free survival(PFS) was 8.53 months versus 5.33 months (p = 0.06) and the median OS was 19.9 months and 7.33 months (p = 0.029), respectively. Three radiomics features were incorporated into the model construction as final variables after LASSO regression analysis. In testing cohort, Logistic Regression (LR) model has the best performance with an Area Under the Curve (AUC) of 0.93 compared with other models, which can effectively predict the response of rMG patients to anlotinib in combination with TMZ. The calibration curve confirmed the agreement between the observed actual and prediction probability. Within the reasonable threshold probability range (0.38–0.88), the radiomics model shows good clinical utility. Conclusions The above-described radiomics model performed well, which can serve as a clinical tool for individualized prediction of the response to anlotinb combined with TMZ in rMG patients.

Background: Fulminant myocarditis (FM) is associated with high mortality and an unfavorable long-term prognosis. However, noninvasive, rapid diagnostic and monitoring methods for FM are lacking. Case summary: This report details the case of a patient diagnosed with FM through a comprehensive assessment involving typical clinical symptoms, laboratory analyses, echocardiographic evidence, and cardiac magnetic resonance (CMR) findings. Before the patient underwent CMR, optical pumped magnetometer magnetocardiography (OPM-MCG) revealed abnormalities characteristic of substantial myocardial injury. After invasive coronary angiography, the patient’s coronary arteries were determined not to exhibit significant stenosis. Additionally, a myocardial bridge was observed in the middle segment of the anterior descending branch of the left coronary artery. Over a 7-month follow-up, the patient’s symptoms showed marked improvement, and the OPM-MCG eventually normalized, aligning with the findings indicated by the CMR. Conclusion: OPM-MCG is a valuable tool for therapy monitoring in FMs, offering a safe, non-invasive, and highly effective test for ancillary diagnostics and long-term prognostic follow-up. Additionally, MCG may potentially assist in clinical decision-making regarding the need for further interventions in patients with myocardial bridge.

Abstract We developed a continuous learning system (CLS) based on deep learning and optimization and ensemble approach, and conducted a retrospective data simulated prospective study using ultrasound images of breast masses for precise diagnoses. We extracted 629 breast masses and 2235 images from 561 cases in the institution to train the model in six stages to diagnose benign and malignant tumors, pathological types, and diseases. We randomly selected 180 out of 3098 cases from two external institutions. The CLS was tested with seven independent datasets and compared with 21 physicians, and the system’s diagnostic ability exceeded 20 physicians by training stage six. The optimal integrated method we developed is expected accurately diagnose breast masses. This method can also be extended to the intelligent diagnosis of masses in other organs. Overall, our findings have potential value in further promoting the application of AI diagnosis in precision medicine.

Precision medicine aims at using target therapy on specific diseases by studying the pathogenesis and finding biomarkers. Inborn errors of immunity (IEI) are caused by single gene mutations, providing the perfect human models to study immunology. The technology rapidly developes recently, so scientists have a deeper understandings of the phenotypes, genotypes, and the biological targets, so that doctors are able to use precision medicine on IEIs with many successful cases. The precision medicine have advantages in the treatment of pathogenesis of diseases. This article summarizes successful cases of using precision medicine for IEI recently.

Chronic granulomatous disease (CGD) is a heterogeneous primary immunodeficiency characterized by severe bacterial and fungal infections and tissue granuloma formation early in life. Diagnosis of CGD involves the granulocyte function assays and gene mutation analysis. X-linked CGD (XL-CGD) caused by gene defects of CYBB is the most prevalent type of CGD. The clinical data and gene characteristics of a rare female X-chromosome mosaicism leading to inheritance of XL-CGD were reported here. The patient is a 7-year-old boy manifested as recurrent lower respiratory tract infection and failed to thrive. The patient had a history of osteo- myelitis and perianal abscess, with Bacille Calmette-Guérin (BCG) vaccine complications. Respiratory burst of neutrophils was measured with DHR oxidation assay and the histogram showing no significant change in neutrophil fluorescence after stimulation of the patient and the mother's histogram had a pattern of 2 peaks after stimulation. A heterozygous mutation in the CYBB gene (c.866G > A, p.W289X) was identified through inheritance from the patient's mother. Genetic analysis from blood and cheek mucosal cells indicated the female was a mosaicism in CYBB with mutation was present in about 19.5% of her leukocytes. We reported the clinical data and gene characteristics of a rare female X-chromosome mosaicism leading to inheritance of XL-CGD for the first time in China to enrich the understanding of XL-CGD and provide new sights for the hereditary counseling.

ObjectiveTumor residue after concurrent chemoradiotherapy (CCRT) in nasopharyngeal carcinoma (NPC) patients often predicts poor prognosis. Thus, the objective of this retrospective study is to develop a nomogram that combines magnetic resonance (MRI) radiomics features and clinical features to predict the early response of locally advanced nasopharyngeal carcinoma (LA-NPC).MethodsA total of 91 patients with LA-NPC were included in this study. Patients were randomly divided into training and validation cohorts at a ratio of 3:1. Univariate and multivariate analyses were performed on the clinical parameters of the patients to select clinical features to build a clinical model. In the training cohort, the Least Absolute Shrinkage and Selection Operator (LASSO) regression model was used to select radiomics features for construction of a radiomics model. The logistic regression algorithm was then used to combine the clinical features with the radiomics features to construct the clinical radiomics nomogram. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were drawn to compare and verify the predictive performances of the clinical model, radiomics model, and clinical radiomics nomogram.ResultsPlatelet lymphocyte ratio (PLR) and nasopharyngeal tumor volume were identified as independent predictors of early response in patients with locally advanced nasopharyngeal carcinoma. A total of 5502 radiomics features were extracted, from which 25 radiomics features were selected to construct the radiomics model. The clinical radiomics nomogram demonstrated the highest AUC in both the training and validation cohorts (training cohort 0.975 vs 0.973 vs 0.713; validation cohort 0.968 vs 0.952 vs 0.706). The calibration curve and DCA indicated good predictive performance for the nomogram.ConclusionA clinical radiomics nomogram, which combines clinical features with radiomics features based on MRI, can predict early tumor regression in patients with LA-NPC. The performance of the nomogram is superior to that of either the clinical model or radiomics model alone. Therefore, it can be used to identify patients without CR at an early stage and provide guidance for personalized therapy.

Employing a small baseline subset Interferometric Synthetic Aperture Radar (SBAS-InSAR) and hotspot analysis, this study identified 81 potential landslides in a 768.7 km2 area of Xiaojin county, eastern Tibetan Plateau. Subsequent time-series deformation analysis revealed that these potential landslides are in the secondary creep stage. The newly identified landslides were compared to a landslide inventory (LI), established through field surveying, in terms of causative factors, including altitude, slope, relief amplitude, distance to river, distance to road, and slope curvature. From the comparison, the InSAR technique showed the following advantages: (1) it identified 25 potential landslides at high altitudes (>3415 m) in addition to the low-altitude landslides identified through the field survey. (2) It obtained approximately 37.5% and 70% increases in the number of potential landslides in the slope angle ranges of 20°–30° and 30°–40°, respectively. (3) It revealed significant increases in potential landslides in every relief amplitude bin, especially in the range from 58 m to 92 m. (4) It can highlight key geological factors controlling landslides, i.e., the stratigraphic occurrence and key joints as the InSAR technique is a powerful tool for identifying landslides in all dip directions. (5) It reveals the dominant failure modes, such as sliding along the soil–rock interface and/or interfaces formed by complicated combinations of discontinuities. This work presents the significant potential of InSAR techniques in gaining deeper knowledge on landslide development in alpine forest regions.

In 2019, the International Classification of Diseases 11th Revision International Classification of Diseases (ICD-11) put forward a new concept of “chronic primary pain” (CPP), a kind of chronic pain characterized by severe functional disability and emotional distress, which is a medical problem that deserves great attention. Although CPP is closely related to depressive disorder, its potential neural characteristics are still unclear. This paper collected EEG data from 67 subjects (23 healthy subjects, 22 patients with depression, and 22 patients with CPP) under the auditory oddball paradigm, systematically analyzed the brain network connection matrix and graph theory characteristic indicators, and classified the EEG and PLI matrices of three groups of people by frequency band based on deep learning. The results showed significant differences in brain network connectivity between CPP patients and depressive patients. Specifically, the connectivity within the frontoparietal network of the Theta band in CPP patients is significantly enhanced. The CNN classification model of EEG is better than that of PLI, with the highest accuracy of 85.01% in Gamma band in former and 79.64% in Theta band in later. We propose hyperexcitability in attentional control in CPP patients and provide a novel method for objective assessment of chronic primary pain.

We investigate the existence and stability of localized gap states at a non-linear interface of non-linear fractional systems in a one-dimensional photonic lattice. By using the direct numerical simulations and linear stability analysis, we obtain the stability of the asymmetric localized gap states in the first and second finite gaps. Our theoretical results show that the power of the localized gap states decrease gradually as the increase of propagation constant and the non-linear landscape (non-linear coefficient ratio between the left and right interface), providing insights into soliton physics in non-linear periodic systems with fractional-order diffraction.

BackgroundsDiabetic retinopathy (DR) is a common diabetic ocular disease characterized by retinal ganglion cell (RGC) changes. An abnormal environment, hyperglycemia, may progressively alter the structure and function of RGCs, which is a primary pathological feature of retinal neurodegeneration in DR. Accumulated studies confirmed autophagy and senescence play a vital role in DR; however, the underlying mechanisms need to be clarified.MethodsThis study included the microarray expression profiling dataset GSE60436 from Gene Expression Omnibus (GEO) to conduct the bioinformatics analysis. The R software was used to identify autophagy-related genes (ARGs) that were differentially expressed in fibrovascular membranes (FVMs) and normal retinas. Co-expression and tissue-specific expression were elicited for the filtered genes. The genes were then analyzed by ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Gene Set Enrichment Analysis (GSEA). R28 cells were cultured with high glucose, detected by reverse transcription-quantitative (RT-qPCR) and stained by apoptosis kit.ResultsIn the retina, 31 differentially expressed ARGs (24 up-regulated genes) were discovered and enriched. The enrichment results revealed that differentially expressed ARGs were significantly enriched in autophagy, apoptosis, aging, and neural function. Four hub genes (i.e., TP53, CASP1, CCL2, and CASP1) were significantly up-regulated. Upregulation of cellular autophagy and apoptosis level was detected in the hyperglycemia model in vitro.ConclusionsOur results provide evidence for the autophagy and cellular senescence mechanisms involved in retinal hyperglycemia injury, and the protective function of autophagy is limited. Further study may favour understanding the disease progression and neuroprotection of DR.

Abstract Background Modified sutureless and glue-free method is an effective and novel surgical approach for pterygium. We aim to evaluate optical quality in pterygium treated with the new method and investigate the clinical application of the Optical Quality Analysis System (OQAS) and Anterior segment optical coherence tomography (AS-OCT) to evaluate the pterygium surgery. Methods A total of 52 eyes of 52 patients with pterygium were randomly divided into 2 groups. After surgical excision, the bare sclera was placed with a tight fit limbal conjunctival autograft fixed via the modified sutureless and glue-free method in group 1 (26 eyes) and conventional sutures in group 2 (26 eyes). Objective scattering index (OSI), modulation transfer function (MTF) and Strehl ratio (SR) were measured using OQAS in both groups during the perioperative period. Pterygium diameter was measured on AS-OCT. Ocular surface disease index (OSDI) questionnaire also was used. Results The group 1 had significantly lower mean OSI, higher mean MTF, and higher mean SR at 1 month and 3 months after surgery (p 0.05). Pterygium diameter positively correlated with OSI (r = 0.528, p

Cold stress signal transduction refers to a process that involves various physiological and molecular changes. Hydrogen peroxide (H2O2) signaling is stimulated by plants in adapting to various environmental stresses. Here, nine respiratory burst oxidase homolog (ClRboh) genes were identified from the watermelon genome. Chilling stress induced increased gene expression of ClRbohD and H2O2 accumulation in watermelon plants. By using virus-induced gene silencing (VIGS), we found that H2O2-induced chilling tolerance is dependent on ClRbohD by increased electrolyte leakage, membrane lipid peroxidation, and reduced photosystem II activity in ClRbohD-silenced plants compared with control. In addition, silencing of 2-Cys peroxiredoxin (Cl2-CP) increased the chilling sensitivity, while exogenous H2O2 treatment compromised the silencing of Cl2-CP-induced photooxidative damage in watermelon plants. The gene expression and enzyme activities of Cu/Zn-SOD and GR were significantly increased in Cl2-CP-silenced plants rather than pV190 control plants upon H2O2 treatment under chilling stress, suggesting that the activation of antioxidant enzymes by H2O2 serves as an alternative pathway to compensate for the deficiency of Cl2-CP during chilling stress response in watermelon.

We herein report what appears to be the first case of fetal non-compaction cardiomyopathy in both ventricles accompanied by a mutation in the calmodulin gene (CALM2). A 25-year-old woman was referred to our hospital at 25+1 weeks of gestation for evaluation of fetal defects. Prenatal echocardiography showed biventricular non-compaction cardiomyopathy with sinus bradycardia. After termination of the pregnancy, fetal biventricular non-compaction cardiomyopathy was confirmed by autopsy and histopathologic examination. Additionally, whole-exome sequencing of genomic DNA demonstrated a de novo heterozygous mutation (c.389A > G; p.D130G) in CALM2, whereas the parents were normal. In this case report, we highlight the importance of prenatal ultrasound and genetic testing in fetal non-compaction cardiomyopathy with arrhythmia.

Summary: As an emerging new class of semiconductor nanomaterials, halide perovskite (ABX3, X = Cl, Br, or I) nanocrystals (NCs) are attracting increasing attention owing to their great potential in optoelectronics and beyond. This field has experienced rapid breakthroughs over the past few years. In this comprehensive review, halide perovskite NCs that are either freestanding or embedded in a matrix (e.g., perovskites, metal-organic frameworks, glass) will be discussed. We will summarize recent progress on the synthesis and post-synthesis methods of halide perovskite NCs. Characterizations of halide perovskite NCs by using a variety of techniques will be present. Tremendous efforts to tailor the optical and electronic properties of halide perovskite NCs in terms of manipulating their size, surface, and component will be highlighted. Physical insights gained on the unique optical and charge-carrier transport properties will be provided. Importantly, the growing potential of halide perovskite NCs for advancing optoelectronic applications and beyond including light-emitting devices (LEDs), solar cells, scintillators and X-ray imaging, lasers, thin-film transistors (TFTs), artificial synapses, and light communication will be extensively discussed, along with prospecting their development in the future.

Chinese nouns lack inflection and cannot reflect the quantitative relationship between singular and plural numbers. However, neural processes of picture naming are different from those of words. We assume that Chinese single and plural picture naming is different, and they may involve quantitative processing. Therefore, Experiment 1 was designed by picking picture naming as the task and Chinese as the target language and compared the accuracy, reaction time, and event-related potentials (ERPs) between single and plural picture naming, where two types of pictures were mixed. Although the T-test showed no significant differences in behavioral data, there were differences in ERPs. ERP differences involved two effects: P1 of 160–180 ms and P2 of 220–260 ms in the parietal-occipital lobe. These differences are suggested to reflect the neural differences in quantitative processing. Therefore, Chinese singular and plural picture naming consists of word production and implicit quantitative processing simultaneously. To explore the relationship between the two processings, we added a semantic factor (inanimate vs. animate items) to the quantity factor of Experiment 1 and carried out Experiment 2, with the observation indexes unchanged. There were no significant differences in behavioral data among the four conditions. After variance analysis, ERPs results indicated an interaction between semantic and quantitative factors in the central area at 180–280 ms. In summary, we suggest that Chinese singular and plural picture naming includes two simultaneous neural processing tasks: word production and quantitative processing, which interact in the central area at 180–280 ms.

Background and aimsEndoscopic submucosal dissection (ESD) is an advanced minimally invasive technique for en bloc resection of superficial gastrointestinal lesions, which is drawn an increasing attention from its emergence. This bibliometric analysis is to evaluate the origin, current hotspots, and research trends on ESD.MethodsA total of 2,131 publications on ESD from 2006 to 2020 were obtained from the Web of Science Core Collection (WoSCC) database. Bibliometric visualization analyses of countries/regions, institutes, authors, journals, references and keywords were performed by CiteSpace V.5.8.R3.ResultsThe quantity of publications on ESD increased significantly during the past 15 years. Japan occupied the leading position in terms of research power. Professor Yutaka Saito, together with the institute he belongs, the Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan, were the most productive author and institute, respectively. Colorectal ESD led the main thematic concentrations in ESD research. The most prolific journal was Gastrointestinal Endoscopy. European ESD Guideline was the most frequently co-cited reference. Guideline, meta-analysis, endoscopic resection, poly-glycolic acid sheet, Barrett's esophagus, fibrin glue, risk and colorectal neoplasm will be the active research hotspots in the future.ConclusionsThese findings provide the trends and frontiers in the field of ESD, as well as valuable information for clinicians and scientists to discover the future perspectives with potential collaborators.

Abstract Background Chimeric antigen receptor T‐cell (CAR‐T) therapy for acute myeloid leukaemia (AML) has thus far been elusive, in part due to target restriction and phenotypic heterogeneity of AML cells. Mutations of the FMS‐like tyrosine kinase 3 (FLT3) and DNA methyltransferase 3A (DNMT3A) genes are common driver mutations that present with a poor prognosis in AML patients. We found that AML patients with FLT3 or DNMT3A mutations had higher expression of CD44 isoform 6 (CD44v6) compared to normal specimens. Therefore, we intended to demonstrate CD44v6 could be a specific option for AML with FLT3 or DNMT3A mutations. Methods Internal tandem duplication (ITD) mutations of FLT3 (FLT3/ITD) knock‐in clone and DNMT3A‐R882H mutant clones of SKM‐1 cells were generated using CRISPR/Cas9 and lentiviral transfection, respectively. CD44v6 CAR‐T cells were constructed by transfecting T cells with lentivirus containing CD44v6 CAR. CD44v6 expression in AML cell lines, AML patients and healthy donors was evaluated by flow cytometry. DNA methylation assays were used to analyse the mechanisms of FLT3 and DNMT3A mutations affecting CD44v6 expression. Results Aberrant overexpression of CD44v6 was observed in AML cell lines with FLT3 or DNMT3A mutations compared to the wild‐type SKM‐1 or K562 cells. AML patients with FLT3 or DNMT3A mutations had higher expression of CD44v6 compared to normal specimens. Then we constructed CD44v6 CAR‐T cells and found that CD44v6 CAR‐T specifically lysed CD44v6+ cells, accompanied by cytokines release. No significant killing effect was observed from CD44v6‐ AML cells and normal cells after co‐culture with CD44v6 CAR‐T. These results were also observed in vivo. Furthermore, we found that FLT3 or DNMT3A mutations induced CD44v6 overexpression by downregulating the CpG methylation of CD44 promoter. Conclusions Collectively, CD44v6 is a promising target of CAR‐T for AML patients with FLT3 or DNMT3A mutations.

ABSTRACT: Background: According to previous studies of male infertility, we found that the association between sexual dysfunction and male infertility was reported rarely and controversially. Aim: We carried out this 1meta-analysis to evaluate the prevalence of sexual dysfunction and the International Index of Erectile Function (IIEF) score in infertile men. Methods: A systematic search of the target literature was conducted using PubMed, EMBASE, and Cochrane Library. Data were analyzed using Review Manager 5.4 software. Standardized mean differences (SMD) with the corresponding 95% confidence intervals (95% CIs) were implemented in 6 controlled studies as a measure of effect size to assess the relationship between sexual dysfunction and male infertility and Odds Ratio (OR) were performed for the morbidity between infertility group and fertility group. Outcomes: Men in infertile group were found with higher prevalence of sexual dysfunction and lower IIEF values than in controls. Results: A meta-analysis of morbidity was performed in 8 of 10 controlled studies. Meta-analysis of the 8 studies found remarkable higher prevalence of sexual dysfunction in men with infertility than in controls (OR = 2.66, 95% confidence interval = 1.69–4.19, P < .0001; I² = 67%, P for heterogeneity = 0.004). Another meta-analysis of evidence suggested that IIEF in infertile men was lower than controls (SMD = −0.47, 95% confidence interval = −0.63 to −0.31, P < .00001; I² = 64%, p for heterogeneity = 0.02). Clinical Implications: We recommend further research based on the relevant criteria of region, sample size, rigorous statistical analysis, and research design. Strengths & limitations: This systematic review is the first to evaluate the prevalence of sexual dysfunction and the score of sexual dysfunction in male infertility. Investigation on the topic is scarce, and only few studies used appropriate measures. Conclusions: Male infertility was associated with an increase in the prevalence of sexual dysfunction. The areas most affected by sexual function were erectile function, orgasm and sexual desire.Liu Y, Wang Y, Dong C, et al. Sexual Dysfunction in Infertile Men: A Systematic Review and Meta-Analysis. Sex Med 2022;XX:XXXXXX.

Flexible and wearable biosensors have received tremendous attention over the past decade owing to their great potential applications in the field of health and medicine. Wearable biosensors serve as an ideal platform for real-time and continuous health monitoring, which exhibit unique properties such as self-powered, lightweight, low cost, high flexibility, detection convenience, and great conformability. This review introduces the recent research progress in wearable biosensors. First of all, the biological fluids often detected by wearable biosensors are proposed. Then, the existing micro-nanofabrication technologies and basic characteristics of wearable biosensors are summarized. Then, their application manners and information processing are also highlighted in the paper. Massive cutting-edge research examples are introduced such as wearable physiological pressure sensors, wearable sweat sensors, and wearable self-powered biosensors. As a significant content, the detection mechanism of these sensors was detailed with examples to help readers understand this area. Finally, the current challenges and future perspectives are proposed to push this research area forward and expand practical applications in the future.

The spring sensible heating (SSH) over the Tibetan Plateau (TP), which can significantly affect the precipitation in China, has experienced three different stages of change, showing significant increasing (1961–1979, Stage I), decreasing (1980–2002, Stage II), and increasing (2003–2014, Stage III) trends. In this study, the impact of these different trends in TP SSH on spring precipitation (SPR) in China and their possible mechanisms are investigated, based on observations and the reanalysis product. In Stage I, the SPR represents a contrasting north-south pattern associated with the increasing TP SSH, showing increasing trends over southern China and decreasing trends over central and northern China. Further, the spatial distribution of SPR trends shows a contrasting east-west pattern in Stage II. That is, persistent weakening TP SSH plays a more crucial role in increasing and decreasing SPR over southwestern and southern China, respectively. However, compared with the significant trend in SPR in Stage III, the regulation of TP SSH on SPR weakens significantly. Dynamically, the increasing TP SSH in Stage I can strengthen the subtropical westerly jet in the upper layer, simultaneously configured with an anomalous cyclone in northeastern China, which deepens the East Asian trough. Thus, anomalous convergence in the upper layer occurs over central and northern China, favoring the downdraft. It then causes more cold and dry air to move southward in the lower troposphere, which then encounters the warm and wet southwest airflows, boosting the updraft over southern China. In Stage II, regression analysis shows that if the TP SSH increases, an anomalous cyclone in the middle and upper troposphere occurs over the western TP, causing the downdraft and less precipitation over southwestern China, while a cyclone in the lower troposphere occurs over the western North Pacific and extends to southern China, promoting the ascending motions and more precipitation in southern China. However, in this stage, TP SSH actually weakens, thus contributing to more precipitation over southwestern China and less precipitation over southern China.

Abstract Background Mitochondrial respiration is organized in a series of enzyme complexes in turn forming dynamic supercomplexes. In Saccharomyces cerevisiae (baker’s yeast), Cox13 (CoxVIa in mammals) is a conserved peripheral subunit of Complex IV (cytochrome c oxidase, CytcO), localized at the interface of dimeric bovine CytcO, which has been implicated in the regulation of the complex. Results Here, we report the solution NMR structure of Cox13, which forms a dimer in detergent micelles. Each Cox13 monomer has three short helices (SH), corresponding to disordered regions in X-ray or cryo-EM structures of homologous proteins. Dimer formation is mainly induced by hydrophobic interactions between the transmembrane (TM) helix of each monomer. Furthermore, an analysis of chemical shift changes upon addition of ATP revealed that ATP binds at a conserved region of the C terminus with considerable conformational flexibility. Conclusions Together with functional analysis of purified CytcO, we suggest that this ATP interaction is inhibitory of catalytic activity. Our results shed light on the structural flexibility of an important subunit of yeast CytcO and provide structure-based insight into how ATP could regulate mitochondrial respiration.

Abstract Background The hypertensive disorders complicating pregnancy (HDCP) is common in patients with polycystic ovary syndrome (PCOS), yet the potential influencing factors remained unclear. We aimed to assess the independent risk factors of HDCP in patients with PCOS, to provide clinical evidences for the management of PCOS. Methods Pregnant PCOS patients treated in our hospital from June 1, 2018 to November 30, 2020 were approached. The personal and clinical characteristics of patients with and without gestational hypertension were evaluated. Logistic regressions were conducted to identify the independent risk factors of HDCP, Receiver operating characteristics (ROC)curve analysis was conducted to evaluate the predicting value. Results A total of 188 PCOS patients were included, the incidence of HDCP in patients with PCOS was 27.66 %. There were significant differences in the age, BMI, family history of hypertension, the history of adverse pregnancy, history of contraceptive pills use and family history of HDCP between HDCP group and no-HDCP group (all p 0.05). Age ≥ 27y(OR2.048, 95 %CI1.121 ~ 3.208), BMI ≥ 24 kg/m2(OR1.463, 95 %CI1.069 ~ 2.011), family history of hypertension(OR2.129, 95 %CI1.093 ~ 3.042), the history of adverse pregnancy(OR2.435, 95 %CI1.264 ~ 4.085), history of contraceptive pills use(OR3.806, 95 %CI1.184 ~ 6.102), family history of HDCP(OR1.934, 95 %CI1.016 ~ 2.774) were the independent risk factors of HDCP in patients with PCOS (all p

Women’s participation in physical activities has been discouraged for a variety of reasons, especially in Muslim countries. This study aims to highlight Pakistani women’s religious beliefs about sports. It focuses on whether their religion contradicts their participation in sporting activities, and it does so by using an adapted version of the Santa Clara Strength of Religious Faith Questionnaire (SCSRFQ) in the theoretical context of feminism in sports. The snowball sampling method was used to select women (n = 357) from the Sindh province of Pakistan, who completed a questionnaire incorporating the SCSRFQ that was specially designed for the current study. The results were unexpected, revealing that religious beliefs have no negative impact on Pakistani women’s participation in sports. Few participants (14 out of 357, 3.9%) believe that religion is an obstacle to their participation in sports. The results of the study challenge the traditional view by most of the previous studies that Islam is against women’s sports. It also challenges cultural limitations, such as some unwritten rules in Pakistani culture according to which women cannot participate in sports. These efforts should lead to enhanced female sports participation in the Pakistani context.

Abstract Background Excessive generation of reactive oxygen species (ROS) in the presence of a defective antioxidant system can induce cellular damage and disrupt normal physiological functions. Several studies have revealed the unfavorable role of ROS in promoting the growth, proliferation, migration, and survival of leukemia cells. In this review study, we summarize the mechanisms of ROS production and its role in leukemogenesis, counteractive effects of antioxidants, and implicate the current ROS-dependent anticancer therapies in acute myeloid leukemia. Body The dysregulation of the redox system is known to play a significant role in the pathogenesis of leukemia. Leukemia cells generate high levels of ROS, which further increases the levels through extra pathways, including mitochondrial deoxyribonucleic mutation, leukemic oncogene activation, increased nicotinamide adenine phosphate hydrogen (NADPH), and cytochrome P450 activities. Aforementioned pathways once activated have shown to promote genomic instability, induce drug resistance to leukemia medical therapy, disease relapse and reduce survival period. The current standard of treatment with chemotherapy employs the pro-oxidant approach to induce apoptosis and promote tumor regression. However, this approach retains several deleterious effects on the subject resulting in degradation of the quality of life. Nevertheless, the addition of an antioxidant as an adjuvant drug to chemotherapy alleviates treatment-related toxicity, increases chemotherapeutic efficacy, and improves survival rates of a patient. Conclusion Acute myeloid leukemia remains a daunting challenge to clinicians. The desire to achieve the maximum benefit of chemotherapy but also improve patient outcomes is investigated. ROS generated through several pathways promotes leukemogenesis, drug resistance, and disease relapse. Chemotherapy, the mainstay of treatment, further upregulates ROS levels. Therefore, the addition of an antioxidant to leukemia medical therapy alleviates toxicity and improves patient outcomes.

Enrofloxacin (ENR) is widely used for treatment and prevention of bacterial pathogen infections in aquatic animals. However, limited knowledge on kinetic disposal process of ENR in crayfish (Procambrus clarkii). Therefore, the objective of this study was to explore the pharmacokinetics (PK) and tissue distribution regularities of ENR and its predominate metabolite, ciprofloxian (CIP), in crayfish following oral (PO) and intramuscular (IM) administrations. ENR and CIP concentrations in crayfish hemolymph and tissues were determined using ultra performance liquid chromatography coupled to fluorescence detection (UPLC-FLR). PK parameters of targets in hemolymph and tissues were calculated using WinNolin software based on the non-compartmental analysis. Comparative PK parameters in hemolymph showed that higher absorption and longer elimination half-life following IM route than PO treatment. For tissue distribution, high concentrations of ENR and CIP were found in hepatopancreas, and ENR and CIP levels in tissues after IM administration were higher than PO administration. The AUC0-∞ ratios of CIP and ENR in crayfish following PO and IM routes were only 1.25% and 3.56% (hemolymph), 0.71% and 6.89% (muscle), 1.03% and 1.75% (hepatopancreas), 0.65% and 6.46% (gill), respectively, and it indicated that crayfish has a low ability to transform ENR to CIP. ENR regimen suggested against susceptible strains with the minimum inhibition concentration (MIC) below 0.72 μg/mL (IM) and 0.50 μg/mL (PO) based on the values of Cmax/MIC > 8 and AUC/MIC > 125. It could serve as reference data for ENR use in crayfish and provide valuable information for the better utilization of ENR in aquatic animals.

Objective. This study evaluated the impact of a novel venipuncture method on vascular parameters of vena basilica to provide a new technical option for the clinical management of difficult venipuncture. Methods. 32 volunteers examined by ultrasound at the Medical Imaging Center of The First People’s Hospital of Nantong, Jiangsu province, from February 2020 to April 2020 were randomly selected. One hand of each patient was ligated with the traditional single tourniquet and the new ligation method for 20 seconds. Then, the distance between the left or right vena basilica and the skin and the diameter of blood vessels were measured by ultrasound. 98 patients with peripheral venipuncture difficulty who were examined by ultrasound of a third-grade hospital from April 2019 to March 2020 were selected and randomly divided into control group (n=49) and experimental group (n=49). The traditional method was used in the control group, and the new peripheral venipuncture was used in the experimental group. The success rate of single puncture, preparation time before puncture, time required for puncture operation, pain reaction during puncture, intravascular congestion after puncture, subcutaneous tissue injury, and vascular reuse rate after puncture were compared between the two methods. Results. The new ligation and puncture method increased the diameter of peripheral superficial vein vessels by 0.51±0.04 mm, and the change of vena basilica diameter was not significantly associated with gender and age of patient. The success rate of single puncture and the vascular reuse rate were significantly higher in the experimental group than in the control group, while the preparation time and venipuncture time, as well as the patient’s pain response, were significantly lower in the experimental group compared to the control group, and the intravascular congestion and subcutaneous tissue injury were lower. In addition, the mean satisfaction score of patients in the experimental group was higher than that of the control group. Conclusion. The new ligation and puncture method was an effective vena basilica dilation technique for filling the peripheral superficial veins, improving puncture success rate of peripheral difficult vein, and reducing patient pain, which was worth popularizing and applying in clinic.

Abstract Background and aims It has been confirmed that remnant-like particle cholesterol (RLP-C) mediates the progression of coronary artery disease (CAD). Currently there is limited information on RLP-C in menopausal women. With the special status of diabetes mellitus (DM) combined with the special body changes of the menopausal women, the RLP-C is particularly important when studying the changes that occurred in response to CAD and its associated risk factors. This study discussed whether RLP-C could be an independent risk factor for menopausal women with CAD and DM. Methods The cohort consisted of 4753 menopausal women who had undergone coronary angiography. Subjects were separated into CAD and non-CAD groups, and univariate and multivariate logistic regression analysis of CAD risk factors were performed. All patients with a history of DM were divided into DM subgroups. Then, the univariate and multivariate logistic regression analysis of the risk factors of CAD and the comparison among age groups in the DM subgroup were performed. After age stratification of the DM group, the Kruskal-Wallis test was used to analyze the differences of various lipid indexes among age groups. Results The multivariate logistic regression showed that RLP-C was an independent risk factor for CAD in menopausal women (OR 1.232, 95%CI 1.070–1.419). In the DM subgroup, it was also found that RLP-C was an independent risk factor for CAD (OR 1.366, 95%CI 1.043–1.791). Kruskal-Wallis test analysis found that RLP-C had no significant difference among three groups (P > 0.05). Conclusions RLP-C was proved to be an independent risk factor for menopausal women with CAD and DM.

Abstract Background Dyslipidemia is a key driver of coronary artery disease (CAD) development. This study aimed to determine whether the atherogenic index of plasma (AIP), a novel comprehensive lipid index, is an independent and reliable predictor of CAD risk in postmenopausal women. Methods A cohort of consecutive 4644 postmenopausal women (aged 50 or above) undergoing coronary angiography (CAG) in Anzhen Hospital (Beijing, China) from January–December 2014 was included in the analysis. Of them, 3039 women were CAD patients, and 1605 were non-CAD subjects. Results Relative to control subjects, TG levels in CAD patients were higher and HDL-C levels were lower. In CAD patients, non-traditional lipid profile values (TC/HDL-C, AI, and AIP) were significantly elevated relative to controls. AIP was positively correlated with TC (r = 0.157), TG (r = 0.835), LDL-C (r = 0.058), non-HDL-C (r = 0.337), TC/HDL-C (r = 0.683), LDL-C/HDL-C (r = 0.437), LCI (r = 0.662), and AI (r = 0.684), and negatively correlated with HDL-C (r = − 0.682) (all P

Low-temperature stress is the main limiting factor of cucurbit crop cultivation as it affects crop yield and quality. The identification of genes involved in cold tolerance is a crucial aspect of pumpkin rootstock breeding. Here, we examined the function of a pumpkin Regulator of Chromosome Condensation 1 (CmRCC1) gene in the root development and cold stress responses of tobacco (Nicotiana benthamiana). CmRCC1 expression was differentially induced in pumpkin root, stem, and leaf under cold stress. Transient transformation showed that CmRCC1 is located in the nucleus. CmRCC1 overexpression in tobacco increased the gravitropic set-point angle in lateral roots, as well as root diameter and volume. The expression of auxin polar transport factors, PIN1 and PIN3, decreased and increased in CmRCC1-overexpressed plants, respectively. Yeast two-hybrid verification and luciferase complementation imaging assay showed that CmRCC1 interacts with CmLAZY1. Furthermore, the decreases in maximum quantum yield of PS II, the effective quantum yield of PS II, and electron transfer rate and the increases in quantum yield of nonregulated energy dissipation and malondialdehyde content were compromised in transgenic plants compared with wild-type plants under cold stress. The results suggest that CmRCC1 plays an important role in the regulation of root architecture and positively modulates cold tolerance.

Background and purpose: Diagnosis of dementia with Lewy bodies (DLB) is highly challenging, primarily due to a lack of valid and reliable diagnostic tools. To date, there is no report of qualitative signature for the diagnosis of DLB. We aimed to develop a blood-based qualitative signature for differentiating DLB patients from healthy controls.Methods: The GSE120584 dataset was downloaded from the public database Gene Expression Omnibus (GEO). We combined multiple methods to select features based on the within-sample relative expression orderings (REOs) of microRNA (miRNA) pairs. Specifically, we first quickly selected miRNA pairs related to DLB by identifying reversal stable miRNA pairs. Then, an optimal miRNA pair subset was extracted by random forest (RF) and support vector machine-recursive feature elimination (SVM-RFE) methods. Furthermore, we applied logistic regression (LR) and SVM to build several prediction models. The model performance was assessed using the receiver operating characteristic curve (ROC) analysis. Lastly, we conducted bioinformatics analyses to explore the molecular mechanisms of the discovered miRNAs.Results: A qualitative signature consisted of 17 miRNA pairs and two clinical factors was identified for discriminating DLB patients from healthy controls. The signature is robust against experimental batch effects and applicable at the individual levels. The accuracies of the-signature-based models on the test set are 82.61 and 79.35%, respectively, indicating that the signature has acceptable discrimination performance. Moreover, bioinformatics analyses revealed that predicted target genes were enriched in 11 Go terms and 2 KEGG pathways. Moreover, five potential hub genes were found for DLB, including SRF, MAPK1, YWHAE, RPS6KA3, and KDM7A.Conclusion: This study provided a blood-based qualitative signature with the potential to be used as an effective tool to improve the accuracy of DLB diagnosis.

The neural mechanisms of cognitive conflicts within various flanker tasks are still unclear, which may be mixed with different effects of short-term associations and long-term associations. We applied a perceptual (color) flanker task and a symbolic (arrow) flanker task to 25 healthy young adults, while the event-related potentials (ERP) and behavioral performance were recorded. The former contains stimulus-stimulus conflict (SSC) of short-term memory (STM) associations, and the latter contains stimulus-response conflict (SRC) of long-term memory (LTM) associations. Both flanker tasks included congruent and incongruent conditions. The reaction time demonstrated the stimulus-response conflict effect in the arrow flanker task without the stimulus-stimulus conflict effect in the color flanker task. The ERP results showed SSC enhanced the frontocentral N2b without behavioral effects. SRC increased the frontocentral P2 but decreased the centroparietal P3b with prolonged reaction time. In the comparison between both tasks, the color flanker task elicited both the centroparietal N2b/N300 and the frontocentral N400, and the arrow flanker task increased the occipital N1. Our findings provide new evidence that different neural mechanisms underlie conflict effects based on different types of memory associations.

Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder, with 30–40% of OCD patients being unresponsive to adequate trials of anti-OCD drugs and cognitive behavior therapy. The aim of this paper is to investigate the efficacy of non-invasive brain stimulation (NIBS) on treating refractory OCD. With PubMed, Embase, PsycInfo, and Cochrane Library used on 15 February 2022, 24 randomized controlled trials involving 663 patients were included. According to this analysis, NIBS including repetitive transcranial magnetic stimulation (rTMS), theta-burst stimulation (TBS), and transcranial direct current stimulation (tDCS), had a moderate effect on the reduction of Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores (SMD = 0.54, 95% CI: 0.26–0.81; p < 0.01). In the subgroup analysis, rTMS seemed to produce a better therapeutic effect (SMD = 0.73, 95% CI: 0.38–1.08; p < 0.01). Moreover, excitatory (SMD = 1.13, 95% CI: 0.24–2.01; p = 0.01) and inhibitory (SMD = 0.81, 95% CI: 0.26–1.36; p < 0.01) stimulation of the dorsolateral prefrontal cortex (DLPFC) both alleviated OCD symptoms. In the secondary outcome of clinical response rates, NIBS treatment led to an increase in response rates (RR = 2.26, 95% CI: 1.57–3.25; p < 0.01).

The Tibetan Plateau (TP) vortex (TPV), one of the crucial weather systems triggering rainfall, plays a key role in modulating precipitation over TP and downstream regions. The role of atmospheric heat source in TPV development is explored by a case study in June 2016, using high-resolution ERA5 reanalysis, black-body temperature (TBB) obtained from the Fengyun-2E (FY-2E) satellite, and precipitation amount from the Tropical Rainfall Measurement Mission (TRMM). The evolutions of TPV can be split into three stages, i.e., generation, development, and pre-moving-off stage. The intensity of TPV increases with fluctuations, with weaker and shallower TPV in the generation stage, strongest in the development stage and deepest in the pre-moving-off stage. Importantly, the genesis of TPV is related to the surface warming center driven by surface sensible heating while its development is primarily dependent on the latent heat of condensation. The main contributor of the latent heat of condensation is further analyzed as a vertical transport of the water vapor that promotes TPV development.

Aim of study: To investigate the content, contamination levels and potential sources of five heavy metals (Hg, Pb, Cd, Cr, As) in sewage sludge from eight wastewater treatment plants (W1 to W8). Area of study: Wuhu, located in southeastern Anhui Province, southeastern China. Material and methods: The sewage sludge pollution assessment employed the single-factor pollution index, Nemerow’s synthetic pollution index, monomial potential ecological risk coefficient and potential ecological risk index. The potential sources among the five heavy metals were determined using the Pearson’s correlation analysis and principal component analysis (PCA). Main results: The mean concentrations of the heavy metals were 0.27 mg/kg (Hg), 70.78 mg/kg (Pb), 3.48 mg/kg (Cd), 143.65 mg/kg (Cr) and 22.17 mg/kg (As). W1, W5 and W6 sewage sludge samples showed the highest levels of heavy metal contamination, and cadmium had the highest contamination level in the study area. Pearson’s correlation analysis and PCA revealed that Pb and Cd mainly derived from traffic emissions and the manufacturing industry and that As and Cr originated from agricultural discharges. Research highlights: The pollution of cadmium in Wuhu should be controlled preferentially. The heavy metal pollution of W1, W5 and W6 sewage treatment plants is relatively high, they should be key prevention targets.

Reduced pain tolerance may be one of the possible explanations for high prevalence of chronic pain among older people. We hypothesized that age-related alterations in pain tolerance are associated with functioning deterioration of the frontal cortex during normal aging. Twenty-one young and 41 elderly healthy participants underwent a tonic heat pain test, during which cerebral activity was recorded using electroencephalography (EEG). Elderly participants were divided into two subgroups according to their scores on executive tests, high performers (HPs; n = 21) and low performers (LPs; n = 20). Pain measures [exposure times (ETs) and perceived pain ratings] and cerebral activity were compared among the three groups. ETs were significantly lower in elderly LPs than in young participants and elderly HPs. Electroencephalographic analyses showed that gamma-band oscillations (GBOs) were significantly increased in pain state for all subjects, especially in the frontal sites. Source analysis showed that GBO increase in elderly LPs was contributed not only by frontal but also by central, parietal, and occipital regions. These findings suggest that better preservation of frontal functions may result in better pain tolerance by elderly subjects.

Sulfamethazine (SMZ) as a broad antibiotic is widely used in livestock and poultry. However, the abuse of SMZ in livestock feed can lead to SMZ residues in food and the resistance of bacteria to drugs. Thus, a method for the detection of SMZ in food is urgently needed. In this study, quantum dot (QD) nanobeads (QBs) were synthesized by encapsulating CdSe/ZnS QDs using a microemulsion technique. The prepared QBs as signal probes were applied in lateral flow immunoassay (LFIA) for the detection of SMZ in chicken and milk. Our proposed method had limits of detection of 0.1138–0.0955 ng/mL and corresponding linear ranges of 0.2–12.5, 0.1–15 ng/mL in chicken and milk samples, respectively. The recovery of LFIA for the detection of SMZ was 80.9–109.4% and 84–101.6% in chicken and milk samples, respectively. Overall, the developed QBs-LFIA had high reliability and excellent potential for rapid and sensitive screening of SMZ in food.

T cell function in cancer patients is usually impaired due to the constitutive activation of immune checkpoint inhibitors. This state is known as ‘exhaustion’ and is often associated with the inefficient control of tumors or persistent infections. In this work, we investigated the role of leukemia cell-derived microvesicles (MVs) in T cell exhaustion. Following incubation with MVs from various sources, all T cell subtypes exhibited the exhaustion phonotype and impaired cytokine secretion in vitro. Mice models also showed the connection between immune checkpoint inhibitors and MV injection. Sequencing and bioinformatics analyses indicated that a number of transcription factors and microRNAs (miRNAs) were attributable to the dysregulation of pathways and exhaustion in T cells. Further work revealed that functional miR-92a-3p, miR-21-5p, miR-16-5p, miR-126 and miR-182-5p in MVs could be delivered into T cells to induce the exhaustion phenotype. SerpinB2, IL-1β and CXCL5, which are mediators of the NF-κB pathway, were identified as the targets of the miRNAs mentioned above. We demonstrated that leukemia-derived MVs could initiate T cell exhaustion via the progressive temporal delivery of multiple exogenous miRNAs into T cells and the subsequent interaction of these miRNAs with their targets. Therefore, MVs can be expected not only to become new indicators of the T cell status in patients but also to be used as novel targets for personalized patient treatment.