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Aim: To investigate the association between metabolically healthy obesity (MHO) and left ventricular geometric remodelling in Chinese children., Materials and Methods: This cross-sectional study used data from two population-based samples in China, including 2871 children aged 6-11 years. Weight status was defined based on body mass index according to the World Health Organization growth chart. Metabolic status was defined based on the 2018 consensus-based criteria proposed by Damanhoury et al. Obes Rev 2018;19:1476-1491 (blood pressure, lipids and glucose). Left ventricular geometric remodelling was determined as concentric remodelling, eccentric hypertrophy, and concentric hypertrophy. Multinomial logistic regression analysis was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) for the association between categories of weight and metabolic status and left ventricular geometric remodelling., Results: Compared with children with metabolically healthy normal weight, those with MHO had higher odds of left ventricular geometric remodelling, with adjusted ORs (95% CIs) of 2.01 (1.23-3.28) for concentric remodelling, 6.36 (4.03-10.04) for eccentric hypertrophy, and 17.07 (7.97-36.58) for concentric hypertrophy. Corresponding ORs (95% CIs) were 2.35 (1.47-3.75), 10.85 (7.11-16.55), and 18.56 (8.63-39.94), respectively, for children with metabolically unhealthy obesity. In contrast, metabolically unhealthy normal weight was not associated with higher odds of left ventricular geometric remodelling. Findings were consistent in sensitivity analyses that used different definitions of weight and metabolic status and left ventricular geometric remodelling., Conclusions: Children with MHO had higher odds of left ventricular geometric remodelling than their metabolically healthy normal weight counterparts. Our findings suggest MHO may not be a benign condition for cardiac health in children., (© 2024 John Wiley & Sons Ltd.)

Introduction: We investigated the impact of metabolic dysfunction-associated steatotic liver disease (MASLD) on cardiovascular structure development in children., Methods: We followed 1,356 children with the mean age of 6.6 years for 4.5 years in Beijing, China. We assessed the association of MASLD with cardiovascular structure (carotid intima-media thickness and left ventricular mass) outcomes at baseline and follow-up., Results: Over follow-up, 59 children had persistent MASLD, 109 had incident MASLD (progression), and 35 had normalization of liver health. Children with MASLD normalization showed a significantly lower mean development in carotid intima-media thickness (0.161 vs 0.188 mm) and left ventricular mass (4.5 vs 12.4 g) than children with persistent MASLD., Discussion: The control of MASLD was associated with improved cardiovascular structure development., (Copyright © 2024 by The American College of Gastroenterology.)

Dearomatization has emerged as a powerful tool for rapid construction of 3D molecular architectures from simple, abundant, and planar (hetero)arenes. The field has evolved beyond simple dearomatization driven by new synthetic technology development. With the renaissance of photocatalysis and expansion of the activation mode, the last few years have witnessed impressive developments in innovative photochemical dearomatization methodologies, enabling skeletal modifications of dearomatized structures. They offer truly efficient and useful tools for facile construction of highly complex structures, which are viable for natural product synthesis and drug discovery. In this review, we aim to provide a mechanistically insightful overview on these innovations based on the degree of skeletal alteration, categorized into dearomative functionalization and skeletal editing, and to highlight their synthetic utilities.

Blood-brain barrier breakdown and ROS overproduction are important events during the progression of ischemic stroke aggravating brain damage. Geraniol, a natural monoterpenoid, possesses anti-apoptotic, cytoprotective, anti-oxidant, and anti-inflammatory activities. Our study aimed to investigate the effect and underlying mechanisms of geraniol in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced human brain microvascular endothelial cells (HBMECs). Apoptosis, caspase-3 activity, and cytotoxicity of HBMECs were evaluated using TUNEL, caspase-3 activity, and CCK-8 assays, respectively. The permeability of HBMECs was examined using FITC-dextran assay. Reactive oxygen species (ROS) production was measured using the fluorescent probe DCFH-DA. The protein levels of zonula occludens-1 (ZO-1), occludin, claudin-5, β-catenin, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) were determined by western blotting. Geraniol showed no cytotoxicity in HBMECs. Geraniol and ROS scavenger N-acetylcysteine (NAC) both attenuated OGD/R-induced apoptosis and increase of caspase-3 activity and the permeability to FITC-dextran in HBMECs. Geraniol relieved OGD/R-induced ROS accumulation and decrease of expression of ZO-1, occludin, claudin-5, and β-catenin in HBMECs. Furthermore, we found that geraniol activated Nrf2/HO-1 pathway to inhibit ROS in HBMECs. In conclusion, geraniol attenuated OGD/R-induced ROS-dependent apoptosis and permeability in HBMECs through activating the Nrf2/HO-1 pathway., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study examines the concentrations and population-normalized mass loads (PNML) of five phthalate esters (PAEs) and four metabolites (mPAEs) in 390 sewage sludge samples collected from two municipal wastewater treatment plants in Beijing between July 2020 and June 2023, amidst the COVID-19 pandemic. Through GC/MS analysis, the compounds were simultaneously quantified, with peak concentrations in 2020. Bis(2-ethylhexyl) phthalate (DEHP) and mono(2-ethyl-5-oxohexyl) phthalate emerged as predominant PAE and mPAE congeners with concentrations of 78.7 µg/g dw and 259 µg/g dw, respectively. DEHP and monobenzyl phthalate had the highest median PNML among PAEs and mPAEs, respectively, at 128 µg/inhabitant/day and 798 µg/inhabitant/day. Linear regression models revealed a positive association between PNML of PAEs and five public health and social measures aimed at mitigating the COVID-19 pandemic. This research contributes to the expanding body of literature by emphasizing the role of wastewater-based epidemiology as a vital tool for monitoring community-level exposure to environmental contaminants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The incidence of ulcerative colitis (UC) has increased globally. As a complex disease, the genetic predisposition for UC could be estimated by the polygenic risk score (PRS), which aggregates the effects of a large number of genetic variants in a single quantity and shows promise in identifying individuals at higher lifetime risk of UC. Here, based on a cohort of 2869 UC cases and 2900 controls with genotype array datasets, we used PRSice-2 to calculate PRS, and systematically analyzed factors that could affect the power of PRS, including GWAS summary statistics, population stratification, and impact of variants. After leveraging a stepwise condition analysis, we eventually established the best PRS model, achieving an AUC of 0.713. Meanwhile, samples in the top 20% of the PRS distribution had a risk of UC more than ten times higher than samples in the lowest 20% (OR = 10.435, 95% CI 8.571-12.703). Our analyses demonstrated that including population-enriched, more disease-associated SNPs and using GWAS summary statistics from similar ethnic background can improve the power of PRS. Strictly following the principle of focusing on one population in all aspects of generating PRS can be a cost-effective way to apply genotype-array-derived PRS to practical risk estimation.

The accurate prediction of adverse drug reactions (ADRs) is essential for comprehensive drug safety evaluation. Pre-trained deep chemical language models have emerged as powerful tools capable of automatically learning molecular structural features from large-scale datasets, showing promising capabilities for the downstream prediction of molecular properties. However, the performance of pre-trained chemical language models in predicting ADRs, especially idiosyncratic ADRs induced by marketed drugs, remains largely unexplored. In this study, we propose MoLFormer-XL, a pre-trained model for encoding molecular features from canonical SMILES, in conjunction with a CNN-based model to predict drug-induced QT interval prolongation (DIQT), drug-induced teratogenicity (DIT), and drug-induced rhabdomyolysis (DIR). Our results demonstrate that the proposed model outperforms conventional models applied in previous studies for predicting DIQT, DIT, and DIR. Notably, an analysis of the learned linear attention maps highlights amines, alcohol, ethers, and aromatic halogen compounds as strongly associated with the three types of ADRs. These findings hold promise for enhancing drug discovery pipelines and reducing the drug attrition rate due to safety concerns.

Predicting disease-related microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) is crucial to find new biomarkers for the prevention, diagnosis, and treatment of complex human diseases. Computational predictions for miRNA/lncRNA-disease associations are of great practical significance, since traditional experimental detection is expensive and time-consuming. In this paper, we proposed a consensual machine-learning technique-based prediction approach to identify disease-related miRNAs and lncRNAs by high-order proximity preserved embedding (HOPE) and eXtreme Gradient Boosting (XGB), named HOPEXGB. By connecting lncRNA, miRNA, and disease nodes based on their correlations and relationships, we first created a heterogeneous disease-miRNA-lncRNA (DML) information network to achieve an effective fusion of information on similarities, correlations, and interactions among miRNAs, lncRNAs, and diseases. In addition, a more rational negative data set was generated based on the similarities of unknown associations with the known ones, so as to effectively reduce the false negative rate in the data set for model construction. By 10-fold cross-validation, HOPE shows better performance than other graph embedding methods. The final consensual HOPEXGB model yields robust performance with a mean prediction accuracy of 0.9569 and also demonstrates high sensitivity and specificity advantages compared to lncRNA/miRNA-specific predictions. Moreover, it is superior to other existing methods and gives promising performance on the external testing data, indicating that integrating the information on lncRNA-miRNA interactions and the similarities of lncRNAs/miRNAs is beneficial for improving the prediction performance of the model. Finally, case studies on lung, stomach, and breast cancers indicate that HOPEXGB could be a powerful tool for preclinical biomarker detection and bioexperiment preliminary screening for the diagnosis and prognosis of cancers. HOPEXGB is publicly available at https://github.com/airpamper/HOPEXGB.

Background: Identification of patients at risk for type 2 diabetes mellitus (T2DM) can not only prevent complications and reduce suffering but also ease the health care burden. While routine physical examination can provide useful information for diagnosis, manual exploration of routine physical examination records is not feasible due to the high prevalence of T2DM., Objectives: We aim to build interpretable machine learning models for T2DM diagnosis and uncover important diagnostic indicators from physical examination, including age- and sex-related indicators., Methods: In this study, we present three weighted diversity density (WDD)-based algorithms for T2DM screening that use physical examination indicators, the algorithms are highly transparent and interpretable, two of which are missing value tolerant algorithms., Patients: Regarding the dataset, we collected 43 physical examination indicator data from 11,071 cases of T2DM patients and 126,622 healthy controls at the Affiliated Hospital of Southwest Medical University. After data processing, we used a data matrix containing 16004 EHRs and 43 clinical indicators for modelling., Results: The indicators were ranked according to their model weights, and the top 25% of indicators were found to be directly or indirectly related to T2DM. We further investigated the clinical characteristics of different age and sex groups, and found that the algorithms can detect relevant indicators specific to these groups. The algorithms performed well in T2DM screening, with the highest area under the receiver operating characteristic curve (AUC) reaching 0.9185., Conclusion: This work utilized the interpretable WDD-based algorithms to construct T2DM diagnostic models based on physical examination indicators. By modeling data grouped by age and sex, we identified several predictive markers related to age and sex, uncovering characteristic differences among various groups of T2DM patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lv, Luo, Huang, Guo, Bai, Yan, Jiang, Zhang, Jing, Chen and Li.)

Temperature sensors are one of the most fundamental sensors and are found in industrial, environmental, and biomedical applications. The traditional approach of reading the resistive response of Positive Temperature Coefficient thermistors at DC hindered their adoption as wide-range temperature sensors. Here, we present a large-area thermistor, based on a flexible and stretchable short carbon fibre incorporated Polydimethylsiloxane composite, enabled by a radio frequency sensing interface. The radio frequency readout overcomes the decades-old sensing range limit of thermistors. The composite exhibits a resistance sensitivity over 1000 °C -1 , while maintaining stability against bending (20,000 cycles) and stretching (1000 cycles). Leveraging its large-area processing, the anisotropic composite is used as a substrate for sub-6 GHz radio frequency components, where the thermistor-based microwave resonators achieve a wide temperature sensing range (30 to 205 °C) compared to reported flexible temperature sensors, and high sensitivity (3.2 MHz/°C) compared to radio frequency temperature sensors. Wireless sensing is demonstrated using a microstrip patch antenna based on a thermistor substrate, and a battery-less radio frequency identification tag. This radio frequency-based sensor readout technique could enable functional materials to be directly integrated in wireless sensing applications., (© 2024. The Author(s).)

Objective: Sense of coherence has significant implications for the mental health of left-behind children in rural China. This study was conducted to explore the impact of physical exercise and social support on sense of coherence in rural left-behind children., Methods: A survey was conducted among 964 rural left-behind children in Hunan Province of China aged 10-15 (Mage = 12.01 ± 1.97 years; 529 girls and 435 boys). AMOS 21.0 software was applied to build the model and perform cross-lagged analysis., Results: Physical exercise and social support in left-behind children predict each other, and physical exercise can positively predict social support and sense of coherence in left-behind children two months later (P < 0.05); social support can significantly positively predict sense of coherence in left-behind children two months later (P < 0.05)., Conclusions: Both physical exercise and social support have an impact on sense of coherence in left-behind children, and physical exercise can affect sense of coherence in left-behind children through the mediating effect of social support., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier Ltd.)

Nowadays, it is still quite difficult to combat glioblastoma, which is one of the most lethal cancers for human beings. Combinatory therapy, which could not only improve therapeutic efficacy and overcome multiple drug resistance but also decrease the threshold therapeutic drug dosage and minimize side effects, would be an appealing candidate for glioblastoma treatment. Herein, we report fluorescence imaging in the second near-infrared window (NIR-II)-guided combinatory photothermal therapy (PTT) and chemotherapy of glioblastoma with a newly formulated nanomedicine termed PATSL . It is composed of temperature-sensitive liposome (TSL) carriers, NIR-II emissive and photothermal aggregation-induced emission (AIE) dyes, and chemotherapeutic paclitaxel (PTX) as well. PATSL shows spherical morphology with diameters of approximately 55 and 85 nm by transmission electron microscopy and laser light scattering, respectively, a zeta potential of -14.83 mV, good stability in both size and photoactivity, strong light absorption with a peak of approximately 770 nm, and bright emission from 900 nm to 1,200 nm. After excitation with an 808-nm laser with good spatiotemporal controllability, PATSL emits bright NIR-II fluorescence signals for tumor diagnosis in vivo , exhibits high photothermal conversion efficiency (68.8%), and triggers drug release of PTX under hypothermia, which assists in efficient tumor ablation in vitro and in vivo . This research demonstrates that "all-in-one" theranostics with NIR-II fluorescence imaging-guided combinatory PTT and chemotherapy is an efficient treatment paradigm for improving the prognosis of brain cancers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Du, Wang, Huang, Li, Roy, Zhang and Guo.)

Background: The stability of the glenohumeral joint is associated with anatomic characteristics including bony structures and soft tissues., Purpose: To compare the differences in specific bony glenohumeral geometries between shoulders with anterior shoulder instability (ASI), unaffected contralateral shoulders, and healthy control shoulders., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Shoulder computed tomography (CT) scans of 36 patients with ASI and 36 matched healthy controls were retrieved and 3-dimensionally reconstructed. We measured the glenoid radius of curvature (GROC) in the anterior-posterior (AP) and superior-inferior directions, humeral head radius of curvature (HROC) in the AP direction, conformity index, glenoid height, glenoid width, glenoid index, stability angle, glenoid version, and glenoid depth. The differences between the groups were statistically calculated. CT scans of the unaffected contralateral shoulders from 21 of the ASI patients were also collected to identify the consistency of the bony structures in bilateral shoulders., Results: Patients with ASI had greater GROC in the AP direction ( P < .001), HROC in the AP direction ( P = .002), glenoid height ( P = .005), and glenoid index ( P < .001) and smaller conformity index ( P < .001), glenoid width ( P = .002), stability angle ( P < .001), and glenoid depth ( P < .001). In addition, the glenoid of the ASI patients was more anteverted compared with that of controls ( P = .001). There was no statistical difference in half the measurements between the bilateral shoulder joints in patients with ASI., Conclusion: In this study, glenohumeral geometric differences were found between ASI patients and healthy control participants. Glenoid curvature and conformity index, based on bilateral comparisons of affected and contralateral shoulders, appear inherent and may predict ASI risk., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was financially supported by the International Cooperation Project of Science and Technology Department of Jilin Province (No. 20200801074GH). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2023.)

Natural products (NPs) represent a treasure trove for drug discovery and development due to their chemical structural diversity and a broad spectrum of biological activities. Uncovering the biological targets and understanding their molecular mechanism of actions are crucial steps in the development of clinical therapeutics. However, the structural complexity of NPs and intricate nature of biological system present formidable challenges in target identification of NPs. Although significant advances have been made in the development of new chemical tools, these methods often require high levels of synthetic skills for preparing chemical probes. This can be costly and time-consuming relaying on operationally complicated procedures and instruments. In recent efforts, we and others have successfully developed an operationally simple and practical chemical tool known as native-compound-coupled CNBr-activated Sepharose 4B beads (NCCB) for NP target identification. In this approach, a native compound readily reacts with commercial CNBr-activated Sepharose 4B beads with a process that is easily performed in any biology laboratory. Based on NCCB, our group has identified the direct targets of more than 60 NPs. In this review, we will elucidate the application scopes, including flavonoids, quinones, terpenoids and others, characteristics, chemical mechanisms, procedures, advantages, disadvantages, and future directions of NCCB in specific target discovery., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Erianin, a bioactive compound extracted from Dendrobium, a traditional Chinese medicine, exhibits remarkable anti-cancer properties through diverse molecular mechanisms and has attracted the attention of medicinal chemists. However, the low solubility in water, rapid metabolism and elimination from the body lead to poor bioavailability of Erianin, and greatly hinder its clinical application. The development of new Erianin derivatives is continuously proceed to improve its anticancer effects. In recent years, although important progress in the development of Erianin and the publication of some reviews in this aspect, the mechanism against various cancers, pharmacokinetic study, structural modification as well as structure-activity relationships have not been thoroughly considered. This review is aimed at providing complete picture regarding the above aspects by reviewing studies from 2000 to 2023.06. This review also supplies some important viewpoints on the design and future directions for the development of Erianin derivatives as possible clinically effective anticancer agents., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background: Cancer has been the leading cause of death since 2010 in China, with increasing incidence, mortality, and burden. We aimed to assess national and subnational changes in the cancer burden from 2005 to 2020 in China using data from the National Mortality Surveillance System., Methods: We extracted data on cancer-related deaths from the National Mortality Surveillance System, which accounts for 24·3% of the country's population with national and provincial representativeness. Data for the surveillance population stratified by age and sex were extracted from the National Bureau of Statistics of China. We estimated mortality and years of life lost (YLLs) for all cancers and for 23 cancer groups by age and sex, nationally, and for 31 provinces in China between 2005 and 2020. We calculated age-standardised mortality and YLL rates using the China 2020 census as the reference population. Average annual percent changes in age-standardised rates for mortality and YLLs were calculated to assess trends over the study period. Decomposition analysis was used to assess the drivers of changes in cancer-related death due to three explanatory components: population growth, population ageing, and age-specific mortality rates in China., Findings: The total number of cancer-related deaths increased by 21·6% to 2 397 772 and YLLs increased by 5·0% to 56 598 975 between 2005 and 2020. The three leading fatal cancer types remained stable for both sexes over the study period: tracheal, bronchus, and lung cancer; liver cancer; and stomach cancer. The fourth and fifth leading cancers also remained stable among males (oesophageal, and colon and rectum), while colon and rectum cancer replaced oesophageal cancer as the fourth and breast cancer replaced colon and rectum cancer as the fifth leading cause of cancer-related death among females. Age-standardised mortality rates and age-standardised YLL rates for almost all cancer types (except for prostate for male and multiple myeloma for female) decreased significantly in both sexes in urban areas. Age-standardised YLL rates increased for about half of all cancers for both sexes in rural areas. Leading fatal types were leukaemia and brain and nervous system cancer in younger groups (aged 0-19 years); liver, tracheal, bronchus, and lung, or breast cancers in middle-aged groups (aged 40-59 years); and tracheal, bronchus, and lung, liver, or stomach cancers in older adults (aged ≥60 years) in 2020. The leading causes of cancer-related mortality varied for each province, with tracheal, bronchus, and lung or liver cancer at the top in 30 provinces., Interpretation: The cancer burden in China appeared to be shifting towards that in high-income countries from 2005 to 2020. Adjustments to existing health plans and actions are needed to reduce the burdens of tracheal, bronchus, and lung cancer or other leading and emerging cancers., Funding: National Key Research and Development Program of China., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Compared to de novo drug discovery, drug repurposing provides a time-efficient way to treat coronavirus disease 19 (COVID-19) that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 main protease (Mpro) has been proved to be an attractive drug target due to its pivotal involvement in viral replication and transcription. Here, we present a graph neural network-based deep-learning (DL) strategy to prioritize the existing drugs for their potential therapeutic effects against SARS-CoV-2 Mpro. Mpro inhibitors were represented as molecular graphs ready for graph attention network (GAT) and graph isomorphism network (GIN) modeling for predicting the inhibitory activities. The result shows that the GAT model outperforms the GIN and other competitive models and yields satisfactory predictions for unseen Mpro inhibitors, confirming its robustness and generalization. The attention mechanism of GAT enables to capture the dominant substructures and thus to realize the interpretability of the model. Finally, we applied the optimal GAT model in conjunction with molecular docking simulations to screen the Drug Repurposing Hub (DRH) database. As a result, 18 drug hits with best consensus prediction scores and binding affinity values were identified as the potential therapeutics against COVID-19. Both the extensive literature searching and evaluations on adsorption, distribution, metabolism, excretion, and toxicity (ADMET) illustrate the premium drug-likeness and pharmacokinetic properties of the drug candidates. Overall, our work not only provides an effective GAT-based DL prediction tool for inhibitory activity of SARS-CoV-2 Mpro inhibitors but also provides theoretical guidelines for drug discovery in the COVID-19 treatment.

Rationale: Fungal periprosthetic joint infections (fPJIs) are relatively uncommon, accounting for approximately 1% of all PJIs. Revision surgery is typically recommended for fungal infections; however, the physical and financial impact on patients is significant. In this report, we present a case of fPJI successfully treated with debridement, antibiotics, and implant retention (DAIR) with a favorable outcome over a 5-year period., Patient Concern: A 56-year-old male patient presented with a non-healing surgical incision 1 week after undergoing primary total knee arthroplasty on the right side., Diagnosis: Microbiological culture of the wound effusion identified Candida parapsilosis. Postoperatively, the patient exhibited a significant decrease in serum albumin levels and poor glycemic control. Both C-reactive protein and erythrocyte sedimentation rate were elevated., Interventions: A comprehensive DAIR procedure was performed, along with continuous closed irrigation using fluconazole for 1 week. The patient received intravenous voriconazole for 4 weeks, followed by oral fluconazole for an additional 3 months., Outcomes: At 1- and 5-year follow-up appointments, the patient C-reactive protein and erythrocyte sedimentation rate levels were within normal limits, and there was no evidence of swelling, erythema, or tenderness in the right knee joint, indicating no signs of infection., Lessons: DAIR is an effective treatment for early fPJIs, and continuous closed irrigation may provide specific advantages. The patient nutritional status plays a crucial role in the management of periprosthetic infections., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Breast cancer is a heterogeneous disease and can be divided into several subtypes with unique prognostic and molecular characteristics. The classification of breast cancer subtypes plays an important role in the precision treatment and prognosis of breast cancer. Benefitting from the relation-aware ability of a graph convolution network (GCN), we present a multi-omics integrative method, the attention-based GCN (AGCN), for breast cancer molecular subtype classification using messenger RNA expression, copy number variation and deoxyribonucleic acid methylation multi-omics data. In the extensive comparative studies, our AGCN models outperform state-of-the-art methods under different experimental conditions and both attention mechanisms and the graph convolution subnetwork play an important role in accurate cancer subtype classification. The layer-wise relevance propagation (LRP) algorithm is used for the interpretation of model decision, which can identify patient-specific important biomarkers that are reported to be related to the occurrence and development of breast cancer. Our results highlighted the effectiveness of the GCN and attention mechanisms in multi-omics integrative analysis and the implement of the LRP algorithm can provide biologically reasonable insights into model decision., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Single-cell sequencing (scRNA-seq) technology provides higher resolution of cellular differences than bulk RNA sequencing and reveals the heterogeneity in biological research. The analysis of scRNA-seq datasets is premised on the subpopulation assignment. When an appropriate reference is not available, such as specific marker genes and single-cell reference atlas, unsupervised clustering approaches become the predominant option. However, the inherent sparsity and high-dimensionality of scRNA-seq datasets pose specific analytical challenges to traditional clustering methods. Therefore, a various deep learning-based methods have been proposed to address these challenges. As each method improves partially, a comprehensive method needs to be proposed. In this article, we propose a novel scRNA-seq data clustering method named AttentionAE-sc (Attention fusion AutoEncoder for single-cell). Two different scRNA-seq clustering strategies are combined through an attention mechanism, that include zero-inflated negative binomial (ZINB)-based methods dealing with the impact of dropout events and graph autoencoder (GAE)-based methods relying on information from neighbors to guide the dimension reduction. Based on an iterative fusion between denoising and topological embeddings, AttentionAE-sc can easily acquire clustering-friendly cell representations that similar cells are closer in the hidden embedding. Compared with several state-of-art baseline methods, AttentionAE-sc demonstrated excellent clustering performance on 16 real scRNA-seq datasets without the need to specify the number of groups. Additionally, AttentionAE-sc learned improved cell representations and exhibited enhanced stability and robustness. Furthermore, AttentionAE-sc achieved remarkable identification in a breast cancer single-cell atlas dataset and provided valuable insights into the heterogeneity among different cell subtypes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In drug discovery and development, the direct target identification of bioactive small molecules plays a significant role for understanding the mechanism of action, predicting the side effects, and rationally designing more potent compounds. However, due to the complicated regulatory processes in a cell together with thousands of biomacromolecules, target identification is always the major obstacle. New methods and technologies are continuously invented to tackle this problem. Nevertheless, the mainly used tools possess several disadvantages. High synthetic skills are typically required to laboriously synthesize a probe for protein enrichment. To detect the ligand-protein interaction by analyzing proteins' responses to proteolytic or thermal treatment, costly and precise instruments are always necessary. Therefore, convenient and practical techniques are urgently needed. Over the past decades, a strategy using native compounds without the requirement of chemical modification, also termed Native-compound-Coupled Affinity Matrix (NCAM), is developing continuously. Two practical tactics based on "label-free" compounds have been invented and used, that is Photo-cross-linked Small-molecule Affinity Matrix (PSAM) and Native-compound-Coupled CNBr-activated Beads (NCCB). Presently, we will elucidate the characteristics, coupling mechanism, advantages and disadvantages, and future prospect of NCAM in specific target identification and validation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Allergic rhinitis (AR) and adenoid hypertrophy (AH) are common nasal diseases in children. Studies have shown that heavy metals are environmental risk factors for nasal diseases, and the pathogenic mechanisms may be related to dysregulation of nasal mucosal microbiota. However, it is unclear how heavy metal exposure relates to the nasal mucosal microbiota in nasal diseases. Therefore, we explored serum metal exposure levels and nasal mucosal microbiota composition in children with different nasal disease, and further studied the potential correlation between metal exposure and disease-related taxa. There were 64 children recruited for this study. The 23 metals concentrations in serum were measured by inductively coupled plasma mass spectrometry, and nasal mucosal bacteria was identified by 16S rRNA sequencing. Nasal diseases (AR and AH) in children were associated with alterations in the abundance and diversity of the nasal mucosal microbiota. The nasal microbiota of children with AR showed lower diversity, while the microbiota of children with AH showed higher diversity. Linear discriminant analysis Effect Size showed 108 differentially abundant taxa between AR and control groups, 35 differentially abundant taxa among large adenoid, moderate adenoid and small adenoid groups. The serum zinc concentration was negatively correlated with Pielou's eveness index and Simpson's Index in children classified by adenoid size. The spearman correlation analysis showed that multiple disease-related taxa were closely associated with metal concentrations in serum. Our findings may support a link between metal exposure and the diversity and composition of nasal bacteria in children with nasal disease, which present new evidence for the effects of metals on children health., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Background: Early feeding practices have a great impact on the growth and development of infants, and the health of mothers. Maternal emotional regulation (ER) is closely related to infant feeding practices. Exploring the relationship between ER strategy and feeding practice can inform early exclusive breastfeeding (EBF) interventions., Methods: Using baseline survey of a longitudinal study, 965 mothers in Chongqing municipality, Guangzhou city, and Huizhou city were enrolled. At baseline, the study used self-administrated questionnaires to investigate the socio-demographic characteristics, maternal ER strategies and feeding practice within 72 h of delivery. Chi-square test and logistic regression were used to determine the associations of the mothers' ER and feeding practices within 72 h postpartum., Results: Among 965 participants, 27.8 % of mothers practiced EBF, and 69.5 % of mothers reported getting breastfeeding education from health providers. The average scores on the cognitive reappraisal and the expressive suppression of the ERQ were 29.95 ± 7.24 and 14.47 ± 5.16 respectively. Multivariable analysis showed women with expressive suppression were less likely to practice EBF (aOR = 0.96, 95%CI: 0.93-0.98, p = 0.002), while receiving breastfeeding education was positively associated with EBF (aOR = 1.52, 95%CI: 1.09-2.12, p = 0.013)., Limitations: Because the study started during the COVID-19 pandemic, the lock-down measures paused recruitments for quite some time reducing the enrollment of participation. The data we used was within 72 h postpartum, hence the period of time to study feeding practices was short., Conclusion: Mothers' ER strategy and breastfeeding education need to be addressed as part of interventions designed to improve EBF rates during the newborn period in China., Competing Interests: Conflict of interest The authors declare that they have no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Few studies have examined the sex differences in left ventricle (LV) structure and physiology from early life stages. We aimed to assess the role of sex and overweight/obesity on left ventricular mass (LVM) and LV volume in Chinese children without preexisting cardiovascular risk factors. We selected 934 healthy children aged 6-8 years from an existing cohort in Beijing, China. Linear regression models were used to regress body mass index (BMI), fat mass, systolic blood pressure, diastolic blood pressure, waist circumference, and visceral fat area (VFA) with LVM, left ventricle end-diastolic volume (LVEDV) and end-systolic volume (LVESV). Higher BMI, fat mass, waist circumference, VFA, and stroke volume (SV) predicted higher LVM, LVEDV, and LVESV in both sexes. Multivariable analysis showed that boys with an elevated BMI had greater LV hypertrophy. LVEDV and LVESV were higher among boys than among girls and increased with higher BMI in both boys and girls. LVEDV and LVESV were associated with VFA in boys. We observed sex differences in LVM, LVESV, and LVEDV among prepubertal children, independent of obesity, with higher values observed in boys. Sex differences in cardiac structure in children may help explain the higher incidence of cardiovascular disease in male adults. Whether interventions to reduce childhood obesity can improve the trajectory of cardiac dynamics is worth investigating.

G protein-coupled receptors (GPCRs) are the largest drug target family. Unfortunately, applications of GPCRs in cancer therapy are scarce due to very limited knowledge regarding their correlations with cancers. Multi-omics data enables systematic investigations of GPCRs, yet their effective integration remains a challenge due to the complexity of the data. Here, we adopt two types of integration strategies, multi-staged and meta-dimensional approaches, to fully characterize somatic mutations, somatic copy number alterations (SCNAs), DNA methylations, and mRNA expressions of GPCRs in 33 cancers. Results from the multi-staged integration reveal that GPCR mutations cannot well predict expression dysregulation. The correlations between expressions and SCNAs are primarily positive, while correlations of the methylations with expressions and SCNAs are bimodal with negative correlations predominating. Based on these correlations, 32 and 144 potential cancer-related GPCRs driven by aberrant SCNA and methylation are identified, respectively. In addition, the meta-dimensional integration analysis is carried out by using deep learning models, which predict more than one hundred GPCRs as potential oncogenes. When comparing results between the two integration strategies, 165 cancer-related GPCRs are common in both, suggesting that they should be prioritized in future studies. However, 172 GPCRs emerge in only one, indicating that the two integration strategies should be considered concurrently to complement the information missed by the other such that obtain a more comprehensive understanding. Finally, correlation analysis further reveals that GPCRs, in particular for the class A and adhesion receptors, are generally immune-related. In a whole, the work is for the first time to reveal the associations between different omics layers and highlight the necessity of combing the two strategies in identifying cancer-related GPCRs., Competing Interests: Declaration of competing interest All authors have declared that no conflict of interest exist., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background Life's Essential 8 (LE8) metrics for cardiovascular health (CVH) aid primordial prevention in US populations. Methods and Results We conducted a child cohort study (PROC [Beijing Child Growth and Health Cohort]) with baseline (2018-2019) and follow-up (2020-2021) assessments, enrolling disease-free 6- to 10-year-old children from 6 elementary schools in Beijing. We collected LE8-assessed components via questionnaire surveys and 3 cardiovascular structural parameters by 2-dimensional M-mode echocardiography: left ventricular mass (LVM), LVM index, and carotid intima-media thickness. Compared with 1914 participants (mean age, 6.6 years) at baseline, we saw lower mean CVH scores at follow-up (n=1789; 8.5 years). Among LE8 components, diet presented the lowest perfect-score prevalence (5.1%). Only 18.6% of participants had physical activity ≥420 min/wk, 55.9% had nicotine exposure, and 25.2% had abnormal sleep duration. Prevalence of overweight/obesity was 26.8% at baseline and 38.2% at follow-up. We noted optimal blood lipid scores in 30.7%, while 12.9% of children had abnormal fasting glucose. Normal BP was 71.6% at baseline and 60.3% at follow-up. LVM (g), LVM index (g/m 2.7 ), and carotid intima-media thickness (mm) were significantly lower in children with high (56.8, 33.2, 0.35) or moderate CVH scores (60.6, 34.6, 0.36), compared with children with low CVH scores (67.9, 37.1, 0.37). Adjusting for age/sex, LVM (β=11.8 [95% CI, 3.5-20.0]; P =0.005), LVM index (β=4.4 [95% CI, 0.5-8.3]; P =0.027), and carotid intima-media thickness (β=0.016 [95% CI, 0.002-0.030]; P =0.028) were higher in the low-CVH group. Conclusions CVH scores were suboptimal, declining with age. LE8 metrics indicated worse CVH in children with abnormal cardiovascular structural measurements, suggesting the validity of LE8 in assessing child CVH. Registration URL: https://www.chictr.org.cn/index.html; Unique identifier: ChiCTR2100044027.

The majority of the biomarkers were associated with the diagnosis of epilepsy and few of them can be applied to predict the response to antiseizure medications (ASMs). In this study, we identified 26 significantly up-regulated genes and 32 down-regulated genes by comparing the gene expression profiles of patients with epilepsy that responded to valproate with those without applying any ASM. The results of gene set enrichment analysis indicated that the ferroptosis pathway was significantly impacted (p = 0.0087) in patients who responded to valproate. Interestingly, the gene NCOA4 in this pathway exhibited significantly different expression levels between the two groups, indicating that NCOA4 could serve as a potential biomarker to better understand the mechanism of valproate resistance. In addition, six up-regulated genes SF3A2, HMGN2, PABPN1, SSBP3, EFTUD2, and CREB3L2 as well as six down-regulated genes ZFP36L1, ACRC, SUB1, CALM2, TLK1, and STX2 also showed significantly different expression patterns between the two groups. Moreover, based on the gene expression profiles of the patients with the treatment of valproate, carbamazepine, and phenytoin, we proposed a strategy for predicting the response to the ASMs by using the Connectivity Map scoring method. Our findings could be helpful for better understanding the mechanisms of drug resistance of ASMs and improving the clinical treatment of epilepsy., (© 2023. Fondazione Società Italiana di Neurologia.)

Xanthine oxidase inhibitors (XOIs) have been widely studied due to the promising potential as safe and effective therapeutics in hyperuricemia and gout. Currently, available XOI molecules have been developed from different experiments but they are with the wide structure diversity and significant varying bioactivities. So it is of great practical significance to present a consensual QSAR model for effective bioactivity prediction of XOIs based on a systematic compiling of these XOIs across different experiments. In this work, 249 XOIs belonging to 16 scaffolds were collected and were integrated into a consensual dataset by introducing the concept of IC 50 values relative to allopurinol (RIC 50 ). Here, extended connectivity fingerprints (ECFPs) were employed to represent XOI molecules. By performing effective feature selection by machine-learning method, 54 crucial fingerprints were indicated to be valuable for predicting the inhibitory potency (IP) of XOIs. The optimal predictor yields the promising performance by different cross-validation tests. Besides, an external validation of 43 XOIs and a case study on febuxostat also provide satisfactory results, indicating the powerful generalization of our predictor. Here, the predictor was interpreted by shapely additive explanation (SHAP) method which revealed several important substructures by mapping the featured fingerprints to molecular structures. Then, 15 new molecules were designed and predicted by our predictor to show superior IP than febuxostat. Finally, molecular docking simulation was performed to gain a deep insight into molecular binding mode with xanthine oxidase (XO) enzyme, showing that molecules with selenazole moiety, cyano group and isopropyl group tended to yield higher IP. The absorption, distribution, metabolism, excretion and toxicity (ADMET) prediction results further enhanced the potential of these novel XOIs as drug candidates. Overall, this work presents a QSAR model for accurate prediction of IP of XOIs, and is expected to provide new insights for further structure-guided design of novel XOIs., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

In pharmaceutical treatment, many non-cardiac drugs carry the risk of prolonging the QT interval, which can lead to fatal cardiac complications such as torsades de points (TdP). Although the unexpected blockade of ion channels has been widely considered to be one of the main reasons for affecting the repolarization phase of the cardiac action potential and leading to QT interval prolongation, the lack of knowledge regarding chemical structures in drugs that may induce the prolongation of the QT interval remains a barrier to further understanding the underlying mechanism and developing an effective prediction strategy. In this study, we thoroughly investigated the differences in chemical structures between QT-prolonging drugs and drugs with no drug-induced QT prolongation (DIQT) concerns, based on the Drug-Induced QT Prolongation Atlas (DIQTA) dataset. Three categories of structural alerts (SAs), namely amines, ethers, and aromatic compounds, appeared in large quantities in QT-prolonging drugs, but rarely in drugs with no DIQT concerns, indicating a close association between SAs and the risk of DIQT. Moreover, using the molecular descriptors associated with these three categories of SAs as features, the structure-activity relationship (SAR) model for predicting the high risk of inducing QT interval prolongation of marketed drugs achieved recall rates of 72.5% and 80.0% for the DIQTA dataset and the FDA Adverse Event Reporting System (FAERS) dataset, respectively. Our findings may promote a better understanding of the mechanism of DIQT and facilitate research on cardiac adverse drug reactions in drug development.

Background: There is growing evidence that aberrant expression of FAM72A contributes to biological dysfunction, especially mitochondrial dysfunction. However, its role in most tumors remains unclear, especially in glioma. Methods: Herein, a high-throughput sequencing approach was used here to identify FAM72A as the target molecule. Next, we detected the protein and mRNA expression levels of FAM72A in normal brain tissue (NBT) as well as different grades of glioma tissue. CCK-8, colony formation, Transwell assays, and Western blotting, were all used to determine the molecular effects of FAM72A on glioma cells. Results: FAM72A was significantly upregulated in glioma, was significantly correlated with WHO grade and was associated with poor clinical outcomes. In functional assays, FAM72A was shown to promote glioma cell growth. Subsequent mechanistic studies indicated that FAM72A promoted glioma progression by regulating mitophagy through the Pink1/Parkin signaling pathway. In addition, FAM72A promoted mitophagy and maintained Pink1 stability through the Pink1/Parkin signaling pathway. Finally, FAM72A promoted tumor immune escape by upregulating PD-L1 expression. Conclusion: All of these data indicate that FAM72A confers an aggressive phenotype and poor prognosis on gliomas. Targeting FAM72A might represent a new therapeutic strategy for glioma., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The Rh(III)-catalyzed addition of the indole C2-H bond to nitroalkenes under an ambient atmosphere is disclosed, providing direct access to a wide range of 2-(2-nitroalkyl)indoles (33 examples) with excellent chemo- and regioselectivity. In addition, pyrrole derivatives also successfully participated in this Friedel-Crafts alkylation reaction. Representative nitroalkane products could be converted into structurally diverse and valuable indole derivatives. Furthermore, a series of control experiments were conducted, and a plausible mechanism was proposed.

Introduction: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. However, different PTC variants reveal high heterogeneity at histological, cytological, molecular and clinicopathological levels, which complicates the precise diagnosis and management of PTC. Alternative splicing (AS) has been reported to be potential cancer biomarkers and therapeutic targets. Method: Here, we aim to find a more sophisticated molecular subclassification and characterization for PTC by integrating AS profiling. Based on six differentially expressed alternative splicing (DEAS) events, a new molecular subclassification was proposed to reclassify PTC into three new groups named as Cluster0, Cluster1 and Cluster2 respectively. Results: An in silico prediction was performed for accurate recognition of new groups with the average accuracy of 91.2%. Moreover, series of analyses were implemented to explore the differences of clinicopathology, molecular and immune characteristics across them. It suggests that there are remarkable differences among them, but Cluster2 was characterized by poor prognosis, higher immune heterogeneity and more sensitive to anti-PD1 therapy. The splicing correlation networks proved the complicated regulation relationships between AS events and splicing factors (SFs). An independent prognostic indicator for PTC overall survival (OS) was established. Finally, three compounds (orantinib, tyrphostin-AG-1295 and AG-370) were discovered to be the potential therapeutic agents. Discussion: Overall, the six DEAS events are not only potential biomarkers for precise diagnosis of PTC, but also the probable prognostic predictors. This research would be expected to highlight the effect of AS events on PTC characterization and also provide new insights into refining precise subclassification and improving medical therapy for PTC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Lan, Li, Pu and Guo.)

Many per- and polyfluoralkyl substances (PFASs) may disrupt maternal thyroid hormone homeostasis in pregnancy. Concerns should be raised regarding the PFASs exposure in pregnant women because thyroid hormones are involved in the early development of the fetus. In this study, we measured the concentrations of 13 PFASs, including five novel short-chain PFASs, in serum from 123 pregnant women in Beijing, China. Linear regression models were used to investigate the association between thyroid-stimulating hormone (TSH) or free thyroxine (FT4) levels and PFASs concentrations under consideration of the impacts of pregnancy-induced physiological factors. We found that perfluorobutanoic acid (PFBA) (β=0.189, 95%CI=-0.039, 0.417, p=0.10) and perfluorodecanoic acid (PFDA) (β=-0.554, 95%CI=-1.16, 0.049, p=0.071) were suggestive of significant association with TSH in thyroid peroxidase antibody (TPOAb) negative women. No association was observed between all PFASs and FT4 levels after controlling for these confounding factors, such as BMI, gestational weight gain and maternal age. These findings suggest that it should pay more attention to the association between thyroid hormone levels and short-chain PFASs concentrations. Future studies could consider a greater sample and the inclusion of other clinical indicators of thyroid function, such as free T3 and total T3., (Copyright © 2021. Published by Elsevier B.V.)

Objective: Our aim in this study was to better understand the intervention effect of Pender's model on the physical and mental health of patients with diabetes mellitus., Methods: According to the principle of Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, various databases, including CNKI, Wanfang Data, SinoMed, VIP, Web of Science, Cochrane, PubMed and ScienceDirect, were searched to collect and select relevant reports for the implementation of a meta-analysis., Results: Ten randomized controlled trials in 6 foreign reports and 4 Chinese reports were included in this study. A total of 863 participants were involved, including 439 in the experimental group and 424 in the control group. Results of the meta-analysis show that Pender's model has a good intervention effect on the health knowledge (Z=3.371, p<0.050), self-management behaviour (Z=3.781, p<0.050) and psychological function (Z=2.902, p<0.050) of patients with diabetes mellitus as compared to the control group. The subgroup analysis showed that the intervention effect on self-management behaviour would not be affected by the measurement tool used (Z=3.295, p=0.001)., Conclusions: Pender's model showed a good intervention effect on the health knowledge, self-management behaviour and psychological function of patients with diabetes mellitus., (Copyright © 2022 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Objective: Small anterior branch of gastrocolic trunk (SABGT) can be occasionally observed during transverse colectomy and right hemicolectomy. Improperly dealing with the branch may lead to unwanted bleeding and affect the operation process. The purposes of this study are to analyze the frequencies and injury of SABGT. Methods: Intact operation data were collected retrospectively from 39 colon cancer patients who underwent curative laparoscopic transverse colectomy or right hemicolectomy. Frequencies and injury of SABGT were analyzed. Results: Eight cases had SABGT, the frequencies of which is 20.5%. Injury of SABGT occurred intraoperatively in 2 patients. Conclusion: We suggest that SABGT should be considered in surgical management. Consciously looking for and properly dealing with the branch can minimize the influence on the operation process.

Introduction: As a malignant brain tumor, glioblastoma (GBM) is characterized by intratumor heterogeneity, a worse prognosis, and highly invasive, lethal, and refractory natures. Immunotherapy has been becoming a promising strategy to treat diverse cancers. It has been known that there are highly heterogeneous immunosuppressive microenvironments among different GBM molecular subtypes that mainly include classical (CL), mesenchymal (MES), and proneural (PN), respectively. Therefore, an in-depth understanding of immune landscapes among them is essential for identifying novel immune markers of GBM., Methods and Results: In the present study, based on collecting the largest number of 109 immune signatures, we aim to achieve a precise diagnosis, prognosis, and immunotherapy prediction for GBM by performing a comprehensive immunogenomic analysis. Firstly, machine-learning (ML) methods were proposed to evaluate the diagnostic values of these immune signatures, and the optimal classifier was constructed for accurate recognition of three GBM subtypes with robust and promising performance. The prognostic values of these signatures were then confirmed, and a risk score was established to divide all GBM patients into high-, medium-, and low-risk groups with a high predictive accuracy for overall survival (OS). Therefore, complete differential analysis across GBM subtypes was performed in terms of the immune characteristics along with clinicopathological and molecular features, which indicates that MES shows much higher immune heterogeneity compared to CL and PN but has significantly better immunotherapy responses, although MES patients may have an immunosuppressive microenvironment and be more proinflammatory and invasive. Finally, the MES subtype is proved to be more sensitive to 17-AAG, docetaxel, and erlotinib using drug sensitivity analysis and three compounds of AS-703026, PD-0325901, and MEK1-2-inhibitor might be potential therapeutic agents., Conclusion: Overall, the findings of this research could help enhance our understanding of the tumor immune microenvironment and provide new insights for improving the prognosis and immunotherapy of GBM patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor LZ declared a shared parent affiliation with the authors HL, JH, ML, KL, XP, YG at the time of the review, (Copyright © 2022 Li, He, Li, Li, Pu and Guo.)

Predicting RNA solvent accessibility using only primary sequence data can be regarded as sequence-based prediction work. Currently, the established studies for sequence-based RNA solvent accessibility prediction are limited due to the available number of datasets and black box prediction. To improve these issues, we first expanded the available RNA structures and then developed a sequence-based model using modified attention layers with different receptive fields to conform to the stem-loop structure of RNA chains. We measured the improvement with an extended dataset and further explored the model's interpretability by analysing the model structures, attention values and hyperparameters. Finally, we found that the developed model regarded the pieces of a sequence as templates during the training process. This work will be helpful for researchers who would like to build RNA attribute prediction models using deep learning in the future., (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Despite the impressive success of deep learning techniques in various types of classification and prediction tasks, interpreting these models and explaining their predictions are still major challenges. In this article, we present an easy-to-use command line tool capable of visualizing and analyzing alternative representations of biological observations learned by deep learning models. This new tool, namely, layerUMAP, integrates autoBioSeqpy software and the UMAP library to address learned high-level representations. An important advantage of the tool is that it provides an interactive option that enables users to visualize the outputs of hidden layers along the depth of the model. We use two different classes of examples to illustrate the potential power of layerUMAP, and the results demonstrate that layerUMAP can provide insightful visual feedback about models and further guide us to develop better models., Competing Interests: The authors have declared no competing interests., (© 2022 The Author(s).)

Abnormally high lymphocyte counts are seen in persons with nonalcoholic fatty liver disease (NAFLD). Gut microbiota dysbiosis is a risk factor for NAFLD. We assessed the gut microbiota of 63 healthy children and 63 children with NAFLD using 16S rRNA gene and metagenomic sequencing to explore the relationships. Compared with healthy children (HC group), the Bacteroidetes, Verrucomicrobia, and Akkermansia were less abundant, while the Actinobacteria were more abundant in children with NAFLD (FLD group). To understand the effect of lymphocytes on the gut microbiota of children with NAFLD, we compared the microbiota of 41 children with NAFLD and high numbers of lymphocytes (FLD&#95;HL group) and 22 children with NAFLD and low numbers of lymphocytes (FLD&#95;LL group). The abundances of Bacteroidetes, Verrucobacterium, and Akkermansia increased and Actinobacteria decreased in the FLD&#95;LL group compared to the FLD&#95;HL group. Akkermansia was negatively correlated with lymphocyte count. NAFLD may disturb the gut microbiota in children through reducing the abundance of Akkermansia and increasing the abundance of proinflammatory bacteria, such as Escherichia-Shigella . Conclusions: High lymphocyte counts are associated with disturbances of gut microbiota and emergence of opportunistic pathogens in children with NAFLD.

What Is Already Known About This Topic?: Men who have sex with men (MSM) bear a disproportionate burden of new human immunodeficiency virus (HIV) infections and young MSM demonstrate parallel internet-driven HIV incident infection and dynamic social network., What Is Added by This Report?: The HIV positive prevalence and incidence among college MSM were 3.8% and 2.9 per 100 person-years, respectively, while these rates were 13.9% and 10.5 per 100 person-years, respectively, among their social contacts. The overall HIV positive prevalence was 7.2% in Northeast China. HIV-positive MSM have comparatively more social contacts than HIV-seronegative MSM., What Are the Implications for Public Health Practice?: Hyper-linkages found in app-based social networks play an important role in HIV transmission via risky sexual behavior and suggest options for online intervention to promote HIV prevention., Competing Interests: No conflicts of interest., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2022.)

Passive smoking exposure in children is prevalent worldwide and exposes children to respiratory and systemic toxins. In this study, we enrolled 568 children to study how secondhand smoke (SHS) might affect children's cardiovascular health in China. The measurement of nicotine and its metabolites in urine showed that 78.9% of children were exposed to SHS. Children exposed to SHS had greater interventricular septum thickness ( p = 0.005) and left ventricular mass index ( p = 0.008) than nonexposed children. Urinary norcotinine levels were associated with increased ascending aorta diameter (β = 0.10, 95%CI 0.02-0.17) and decreased left ventricular end systolic diameter (β = -0.10, 95%CI -0.19 to -0.01). The effects of SHS exposure on cardiovascular function: norcotinine levels associated with lower left ventricular mass index (β = -0.32, 95%CI -0.59 to -0.05), left ventricular end diastolic volume index (β = -0.43, 95%CI -0.85 to -0.02), and left ventricular end systolic volume index (β = -0.20, 95%CI -0.37 to -0.03). Moreover, there no no significant associations of nicotine, cotinine, and trans -3'-hydroxycotinine with cardiovascular health. Overall, SHS exposure in children remains prevalent in Beijing and may affect children's cardiovascular development, in both structure and function. It suggests that stricter and practical measures are needed toward the elimination of tobacco use in children's environments.

Understanding the protein-RNA interaction mechanism can help us to further explore various biological processes. The experimental techniques still have some limitations, such as the high cost of economy and time. Predicting protein-RNA-binding sites by using computational methods is an excellent research tool. Here, we developed a universal method for predicting protein-specific RNA-binding sites, so one general model for a given protein was constructed on a fixed dataset by fusing the data of different experimental techniques. At the same time, information theory was employed to characterize the sequence conservation of RNA-binding segments. Conversation difference profiles between binding and nonbinding segments were constructed by information entropy (IE), which indicates a significant difference. Finally, the 19 proteins-specific models based on random forest (RF) were built based on IE encoding. The performance on the independent datasets demonstrates that our method can obtain competitive results when compared with the current best prediction model., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Yue Ji et al.)

Prostate cancer (PRAD) is a common and fatal malignancy. It is difficult to manage clinically due to drug resistance and poor prognosis, thus creating an urgent need for novel therapeutic targets and prognostic biomarkers. Although G protein-coupled receptors (GPCRs) have been most attractive for drug development, there have been lack of an exhaustive assessment on GPCRs in PRAD like their molecular features, prognostic and therapeutic values. To close this gap, we herein systematically investigate multi-omics profiling for GPCRs in the primary PRAD by analyzing somatic mutations, somatic copy-number alterations (SCNAs), DNA methylation and mRNA expression. GPCRs exhibit low expression levels and mutation frequencies while SCNAs are more prevalent. 46 and 255 disease-related GPCRs are identified by the mRNA expression and DNA methylation analysis, respectively, complementing information lack in the genome analysis. In addition, the genomic alterations do not exhibit an observable correlation with the GPCR expression, reflecting the complex regulatory processes from DNA to RNA. Conversely, a tight association is observed between the DNA methylation and mRNA expression. The virtual screening and molecular dynamics simulation further identify four potential drugs in repositioning to PRAD. The combination of 3 clinical characteristics and 26 GPCR molecular features revealed by the transcriptome and genome exhibit good performance in predicting progression-free survival in patients with the primary PRAD, providing candidates as new biomarkers. These observations from the multi-omics analysis on GPCRs provide new insights into the underlying mechanism of primary PRAD and potential of GPCRs in developing therapeutic strategies on PRAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Chen, Chen, Yu, Guo, Li and Pu.)

Healthy diet patterns have a positive effect on chronic non-communicable diseases in the pediatric population, but the evidence is limited on the association between kidney impairment and adherence to a Mediterranean diet. We aim to determine the associations between Mediterranean diet adherence and longitudinal tubular and glomerular impairment in children. Based on four waves of urine assays conducted from October 2018 to November 2019, we assayed urinary β 2 -microglobulin (β 2 -MG) and microalbumin (MA) excretion to determine transient renal tubular and glomerular impairment during the follow-up of the child cohort (PROC) study in Beijing, China. We assessed Mediterranean diet adherence using the 16-item Mediterranean Diet Quality Index in children and adolescents (KIDMED) among 1914 primary school children. Poor, intermediate, and good adherence rates for the Mediterranean diet were 9.0% (KIDMED index 0-3), 54.4% (KIDMED index 4-7) and 36.5% (KIDMED index 8-12), respectively. A short sleep duration was more prevalent in children with lower Mediterranean diet adherence, with no significant differences presenting in the other demographic and lifestyle covariates. The results of linear mixed-effects models showed that a higher urinary MA excretion was inversely associated with a higher KIDMED score (β = -0.216, 95%CI: -0.358, -0.074, p = 0.003), after adjusting for sex, age, BMI z-score, SBP z-score, screen time, sleep duration and physical activity. Furthermore, in generalized linear mixed-effects models, consistent results found that transient renal glomerular impairment was less likely to develop in children with intermediate Mediterranean diet adherence (aOR = 0.68, 95%CI: 0.47, 0.99, p = 0.044) and in children with good Mediterranean diet adherence (aOR = 0.60, 95%CI: 0.40, 0.90, p = 0.014), taking poor Mediterranean diet adherence as a reference. We visualized the longitudinal associations between each item of the KIDMED test and kidney impairment via a forest plot and identified the main protective eating behaviors. Children who adhere well to the Mediterranean diet have a lower risk of transient glomerular impairment, underscoring the necessity of the early childhood development of healthy eating patterns to protect kidney health., Competing Interests: The authors declare no conflict of interest related to this work. The funders had no role in the study design; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Undoubtedly, teachers remain at the forefront of implementing rural education. This indicates the significant impact their job involvement has on the overall achievements of schools in rural areas. Studies have found that teachers in rural areas often face more difficulties and fewer opportunities in their work. In general, they need a stronger ability to tolerate delay of gratification if they want to have higher job involvement. However, there is currently insufficient research on the impact of career delay of gratification on teachers' job involvement. This study has been conducted to explore the relationship between the delay of gratification and the level of job involvement among physical education (PE) teachers in rural areas, as well as the mediating effect of job satisfaction. 530 PE teachers in the rural areas of Hunan Province, China, have been selected through random sampling as the participants of this study. They have been required to anonymously fill in a Delay of Gratification Scale, Job Involvement Scale and Job Satisfaction Scale to collect the data for investigation and analysis. The study found positive correlations among delay of gratification, job satisfaction, and job involvement among PE teachers in rural areas (P < 0.01), with job satisfaction playing a partial mediating role and intervening variable in the relationship between delay of gratification and job involvement (P < 0.01). Ultimately, delays in gratification directly and, through job satisfaction, indirectly promotes the job involvement of the teachers. The findings of this study reveal the impacts of delaying gratification on the job involvement of PE teachers in rural areas and provide a theoretical basis for increasing the job involvement of PE teachers in rural areas., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Objectives: School-aged children may experience hearing loss and emotional problems. Previous studies have shown a bidirectional relationship between hearing loss and emotional problems in the elderly population, and we aimed to analyze the association between hearing thresholds and emotional problems in school-aged children., Methods: Based on the Beijing Child Growth and Health Cohort (PROC) study, the hearing screenings were conducted in November 2019 using pure tone audiometry. A total of 1,877 parents completed the Strengths and Difficulties Questionnaire (SDQ) to assess children's emotional and behavioral status. We used generalized linear regression analysis to assess the potential association of emotional problems with hearing thresholds, based on multiple imputed datasets with a sample size of 1,914., Results: The overall pass rate of hearing screening was 91.5%. The abnormal rate of SDQ total difficulties was 55.8%. Emotional symptoms were positively associated with left ear average hearing thresholds (β = 0.24, 95% CI : 0.08-0.40), and right ear average hearing thresholds (β = 0.18, 95% CI : 0.04-0.32). Conduct problems, hyperactivity/inattention, peer problems, and prosocial behaviors had no association with the pass rate of the hearing screening. Regarding emotional symptoms, boys with many fears and who are easily scared coincided with increased right ear average hearing thresholds (β = 0.67, 95% CI : 0.01-1.33). Girls having many worries, frequently feeling unhappy and downhearted were positively associated with left and right ear average hearing thresholds, respectively (β = 0.96, 95% CI : 0.20-1.73; β = 0.72, 95% CI : 0.07-1.37)., Conclusions: The co-occurrence of hearing problems and emotional problems of children aged 6-8 in Beijing attracts attention. It is important to address undiscovered hearing loss and emotional problems from the perspective of comorbidity driving factors., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xiao, Amaerjiang, Wang, Li, Zunong, En, Zhao, Wen, Yu, Huang and Hu.)

Background: Emergency cesarean section (EMCS) and breastfeeding difficulties increase the risk of postpartum depressive (PPD) symptoms. Early initiation of breastfeeding (EIBF) may not only alleviate PPD symptoms but also facilitate subsequent breastfeeding success. EMCS is a risk factor for not practicing EIBF. Therefore, it is important to understand the relationship between EMCS, EIBF, and PPD symptoms. Methods: We conducted a prospective cohort study in three areas of China. At baseline, a total of 965 mothers completed electronic questionnaires within 72 h postpartum. Women were screened for PPD symptoms using the Edinburgh Postpartum Depression Scale (EPDS). Multivariate logistic regression was used to identify the determinants of PPD symptoms. Mediation analysis was used to determine if EIBF mediated the relationship between delivery mode or breastfeeding education source and PPD symptoms. Results: The prevalence of EIBF was 40.6%; 14% of 965 mothers experienced EMCS, and 20.4% had PPD symptoms. The risk factors for developing PPD symptoms were excessive gestational weight gain (adjusted odds ratio [aOR] = 1.55, confidence interval [95% CI]: 1.03−2.33, p = 0.037) and EMCS (aOR = 2.05, 95% CI: 1.30−3.25, p = 0.002). The protective factors for developing PPD symptoms were monthly household income over CNY 10000 (aOR = 0.68, 95% CI: 0.47−0.97, p = 0.034), EIBF (aOR = 0.49, 95% CI: 0.34−0.72, p < 0.001), and prenatal breastfeeding education from nurses (aOR = 0.46, 95% CI: 0.29−0.73, p = 0.001). EIBF indirectly affected PPD symptoms in patients who had undergone EMCS (percentage mediated [PM] = 16.69, 95% CI: 7.85−25.25, p < 0.001). The source of breastfeeding education through EIBF also affected PPD symptoms (PM = 17.29, 95% CI: 3.80−30.78, p = 0.012). Conclusion: The association between EMCS on PPD symptoms was mediated by EIBF. By providing breastfeeding education, nurses could also help alleviate PPD symptoms.