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Abstract The relative risk and benefits of Laparoscopic liver resection (LLR) are still controversial. This study aimed to evaluate perioperative and survival outcomes for three primary malignant liver tumors related outcomes following LLR. Data from three Homogeneous-High-Volume-Expert-Centers were collected. Multivariable logistic regression analysis was performed for the association between LLR, and major complications defined as Clavien-Dindo Classification grade ≥ II. Multivariable Cox proportional hazards regression was used to explore the impact of LLR on primary malignant liver tumor survival. Overall, 5886 patients underwent liver resection, of which 1991 underwent LLR. After adjusting for covariables, LLR had significantly lower rate of CDC grade ≥ II (OR = 0.56, 95% CI: 0.48–0.67, P 0.05). LLR was associated with lower rate of major complications, especially in women, non-drinkers, those without a history of abdominal surgery, and those with normal platelet. For primary malignant liver tumors, the survival outcomes did not differ significantly between LLR and OLR.

Abstract CDK4/6 inhibitors are standard of care in the treatment of metastatic breast cancer. Treatment regimen consists of a combination with endocrine therapy, since their therapeutic efficacy as monotherapy in most clinical trials was rather limited. Thus, understanding the molecular mechanisms that underlie response to therapy might allow for the development of an improved therapy design. We analyzed the response to the CDK4/6 inhibitor palbociclib in bladder cancer cells over a 48-hour time course using RNA sequencing and identified a multi-step mechanism of response. We next translated these results to the molecular mechanism in bladder cancer cells upon PD treatment. The initial step is characterized by translocation of the RB protein into the nucleus by activation of importin α/β, a mechanism that requires the NLS sequence. In parallel, RB is proteolyzed in the cytoplasm, a process regulated by gankyrin and the SCF complex. Only hypophosphorylated RB accumulates in the nucleus, which is an essential step for an efficient therapy response by initiating G1 arrest. This might explain the poor response in RB negative or mutated patients. At later stages during therapy, increased expression of the MiT/TFE protein family leads to lysosomal biogenesis which is essential to maintain this response. Lastly, cancer cells either undergo senescence and apoptosis or develop mechanisms of resistance following CDK4/6 inhibition.

Antibodies targeting non-structural protein 1 (NS1) confer protection against Zika virus (ZIKV). Although monoclonal antibodies (MAbs) 3G2 and 4B8 are more potent than MAb 4F10 in suppressing ZIKV infection in neonatal mice models, the epitopes are unclear. Herein, we determined the Cryo-electron microscopy (Cryo-EM) structures of ZIKV NS1 in complex with five human antibodies at 2.6–2.9 Å resolution. Group I antibodies (3G2 and 4B8) recognize the previously unreported epitopes on the outer surface of the NS1 dimer. The unique binding mode of Group I antibodies led to a stronger recognition of the cell surface form of NS1 and completely inhibited secreted form non-structural protein 1 (sNS1)-induced endothelial permeability via their immunoglobulin G (IgG) and Fab. Group II antibodies (4F10, 2E11, and 14G5) recognize common epitopes in the distal end of the β-ladder domain, with a blockade efficiency that may be related to their affinity for the sNS1 protein and the presence of full-length IgG. These findings elucidate the correlation between epitope recognition and protective efficacy of anti-NS1 antibodies and highlight the diagnostic and therapeutic potential of 3G2 and 4B8.

Abstract Objectives General practitioners are trained to care for patients with a high level of responsibility and professional competency. However, there are few reports on the physical and mental health status of general practitioners (GPs) in China, particularly regarding help seeking and self-treatment. The primary aims of this study were to explore GPs’ expectations of their own family doctors and their reflection on role positioning, and to explore the objective factors that hinder the system of family doctors. Study design Cross-sectional study. Methods We conducted an online survey of Chinese GPs. Descriptive statistics were used to summarize the findings. Results More than half of the participants (57.20%) reported that their health was normal over the past year. A total of 420 participants (23.35%) reported having chronic diseases. For sleep duration, 1205 participants (66.98%) reported sleeping 6–8 h per day; 473 participants (26.29%) reported chronic insomnia. Two hundred thirty-one participants (12.84%) had possible depression. A total of 595 (33.07%) participants reported that they had contracted a fixed family doctor. In terms of preventing themselves from contracting for a family doctor, the following factors were identified: lack of sufficient time (54.81%), could solve obstacles themselves (50.97%), and embarrassment (24.24%). The proportion of the contract group (12.44%) taking personal relationship as a consideration was higher than that of the non-contract group (7.64%) (χ2 = 10.934 P = 0.01). Most participants (79.90%) in the non-signed group reported never having seen a family doctor. In terms of obstacles, more than half of the signed group thought that they could solve obstacles themselves, while the non-signed group (39.20%) was less confident in the ability of family doctors than the signed group (29.75%) (χ2 = 15.436, P

Abstract Background Evidence has revealed a connection between cuproptosis and the inhibition of tumor angiogenesis. While the efficacy of a model based on cuproptosis-related genes (CRGs) in predicting the prognosis of peripheral organ tumors has been demonstrated, the impact of CRGs on the prognosis and the immunological landscape of gliomas remains unexplored. Methods We screened CRGs to construct a novel scoring tool and developed a prognostic model for gliomas within the various cohorts. Afterward, a comprehensive exploration of the relationship between the CRG risk signature and the immunological landscape of gliomas was undertaken from multiple perspectives. Results Five genes (NLRP3, ATP7B, SLC31A1, FDX1, and GCSH) were identified to build a CRG scoring system. The nomogram, based on CRG risk and other signatures, demonstrated a superior predictive performance (AUC of 0.89, 0.92, and 0.93 at 1, 2, and 3 years, respectively) in the training cohort. Furthermore, the CRG score was closely associated with various aspects of the immune landscape in gliomas, including immune cell infiltration, tumor mutations, tumor immune dysfunction and exclusion, immune checkpoints, cytotoxic T lymphocyte and immune exhaustion-related markers, as well as cancer signaling pathway biomarkers and cytokines. Conclusion The CRG risk signature may serve as a robust biomarker for predicting the prognosis and the potential viability of immunotherapy responses. Moreover, the key candidate CRGs might be promising targets to explore the underlying biological background and novel therapeutic interventions in gliomas.

Abstract Background Metastasis renal cell carcinoma (RCC) patients have extremely high mortality rate. A predictive model for RCC micrometastasis based on pathomics could be beneficial for clinicians to make treatment decisions. Methods A total of 895 formalin-fixed and paraffin-embedded whole slide images (WSIs) derived from three cohorts, including Shanghai General Hospital (SGH), Clinical Proteomic Tumor Analysis Consortium (CPTAC) and Cancer Genome Atlas (TCGA) cohorts, and another 588 frozen section WSIs from TCGA dataset were involved in the study. The deep learning-based strategy for predicting lymphatic metastasis was developed based on WSIs through clustering-constrained-attention multiple-instance learning method and verified among the three cohorts. The performance of the model was further verified in frozen-pathological sections. In addition, the model was also tested the prognosis prediction of patients with RCC in multi-source patient cohorts. Results The AUC of the lymphatic metastasis prediction performance was 0.836, 0.865 and 0.812 in TCGA, SGH and CPTAC cohorts, respectively. The performance on frozen section WSIs was with the AUC of 0.801. Patients with high deep learning-based prediction of lymph node metastasis values showed worse prognosis. Conclusions In this study, we developed and verified a deep learning-based strategy for predicting lymphatic metastasis from primary RCC WSIs, which could be applied in frozen-pathological sections and act as a prognostic factor for RCC to distinguished patients with worse survival outcomes.

Accurate line parameters are critical for and dispatch in distribution systems. External operating condition variations affect line parameters, reducing the accuracy of state estimation and power flow calculations. While many methods have been proposed and obtained results rather acceptable, there is room for improvement as they don’t fully consider line connections in known topologies. Furthermore, inaccuracies in measurement devices and data acquisition systems can introduce noise and outliers, impacting the reliability of parameter identification. To address these challenges, we propose a line parameter identification method based on Graph Attention Networks and Multi-gate Mixture-of-Experts. The topological structure of the power grid and the capabilities of modern data acquisition equipment are utilized to capture. We also introduce a multi-task learning framework to enable joint training of parameter identification across different branches, thereby enhancing computational efficiency and accuracy. Experiments show that the GAT-MMoE model outperforms traditional methods, with notable improvements in both accuracy and robustness.

BackgroundPatients with osteoporosis (OP) are often associated with decreased hand grip strength and increased risk of falling. It remains unclear whether there is a genetic causal between hand grip strength and OP, falling risk.MethodsThe Mendelian randomization study was used to investigate the genetic causal effect of low hand grip strength on total body bone mineral density (BMD) at different ages, OP, and falling risk. Genes for low hand grip strength, total body BMD at different ages, OP, and falling risk were obtained from published genome-wide association studies. Inverse variance weighted, MR‐Egger, and weighted median were applied to perform the MR analysis. The Cochran’s Q test, MR‐Egger intercept test, MR-PRESSO global test, and leave-one-out analysis were used to detect the pleiotropy or heterogeneity.ResultsThe results showed strong evidence that low hand grip strength was positively associated with OP (OR: 1.006, 95% CI: 1.003-1.010; P= 0.0001) and falling risk (OR: 1.069, 95% CI: 1.013-1.129; P= 0.0160), and could not directly affect the different ages of total body BMD (P> 0.05). There was no heterogeneity or horizontal pleiotropy in the sensitivity analysis (all P> 0.05).ConclusionThe study found a positive causal relationship between low hand grip strength and higher risk of OP and falling, which should be taken into account in the development of future prevention and screening strategies for OP and falling.

BackgroundTo explore the dynamic changes and trends in the body shape of Hmong children aged 7–12 years from 1985 to 2019, and to predict them, to provide a reference for the physical health level of Hmong children.MethodsThe body shape data of Hmong children aged 7–12 years old from the Chinese National Survey on Students’ Constitution and Health (CNSSCH) in 1985, 1991, 1995, 2000, 2005, 2010, 2014, and 2019 were used for longitudinal comparative analysis, and the grey GM(1,1) model was established based on this as a time series. Forecast the future development trend in 2025 and 2030.Results1) From 1985 to 2019, all indicators of body shape of Hmong primary school students showed an upward trend, the increase in height (FBoys = 3.91, p > 0.05; FGirls = 3.91, p > 0.05), weight (FBoys = 8.04, p BMI > Height, girls grow faster than boys; 2) The prevalence of overweight and obesity increased year by year, from 5.2 and 1.2% in 1991 to 12.4% (χ2linear trend = 3.89, p

Abstract Endosymbionts regulate the behavior of pest species, which could provide insights into their control. The citrus leafminer (Phyllocnistis citrella Stainton) is a widely distributed pest associated with diseases of citrus, especially of young trees. Here, we determined the endosymbiont composition of P. citrella in citrus orchards across China. The resulting dataset comprised average 50,430 high-quality reads for bacterial 16S rRNA V3-V4 regions of endosymbionts from 36 P. citrella larvae sampled from 12 citrus orchards across China. The sequencing depth and sampling size of this dataset were sufficient to reveal most of the endosymbionts of P. citrella. In total, 2,875 bacterial amplicon sequence variants were obtained; taxonomic analysis revealed a total of 372 bacterial genera, most of which were Proteobacteria phylum with Undibacterium being the most abundant genus. This dataset provides the first evidence of P. citrella endosymbionts that could support the development of pest management approaches in citrus orchards.

Abstract Rosa roxburghii Tratt, a valuable plant in China with long history, is famous for its fruit. It possesses various secondary metabolites, such as L-ascorbic acid (vitamin C), alkaloids and poly saccharides, which make it a high nutritional and medicinal value. Here we characterized the chromosome-level genome sequence of R. roxburghii, comprising seven pseudo-chromosomes with a total size of 531 Mb and a heterozygosity of 0.25%. We also annotated 45,226 coding gene loci after masking repeat elements. Orthologs for 90.1% of the Complete Single-Copy BUSCOs were found in the R. roxburghii annotation. By aligning with protein sequences from public platform, we annotated 85.89% genes from R. roxburghii. Comparative genomic analysis revealed that R. roxburghii diverged from Rosa chinensis approximately 5.58 to 13.17 million years ago, and no whole-genome duplication event occurred after the divergence from eudicots. To fully utilize this genomic resource, we constructed a genomic database RroFGD with various analysis tools. Otherwise, 69 enzyme genes involved in L-ascorbate biosynthesis were identified and a key enzyme in the biosynthesis of vitamin C, GDH (L-Gal-1-dehydrogenase), is used as an example to introduce the functions of the database. This genome and database will facilitate the future investigations into gene function and molecular breeding in R. roxburghii.

Abstract Background Dendrobium huoshanense, a traditional medicinal and food plant, has a rich history of use. Recently, its genome was decoded, offering valuable insights into gene function. However, there is no comprehensive gene functional analysis platform for D. huoshanense. Result To address this, we created a platform for gene function analysis and comparison in D. huoshanense (DhuFAP). Using 69 RNA-seq samples, we constructed a gene co-expression network and annotated D. huoshanense genes by aligning sequences with public protein databases. Our platform contained tools like Blast, gene set enrichment analysis, heatmap analysis, sequence extraction, and JBrowse. Analysis revealed co-expression of transcription factors (C2H2, GRAS, NAC) with genes encoding key enzymes in alkaloid biosynthesis. We also showcased the reliability and applicability of our platform using Chalcone synthases (CHS). Conclusion DhuFAP ( www.gzybioinformatics.cn/DhuFAP ) and its suite of tools represent an accessible and invaluable resource for researchers, enabling the exploration of functional information pertaining to D. huoshanense genes. This platform stands poised to facilitate significant biological discoveries in this domain.

BackgroundMigraine patients have an increased long-term risk of cardio and cerebrovascular events. However, whether these patients are more susceptible to white matter lesions (WMLs) remains debated. To explore this question, our study assessed the proportion of RLS in migraine patients and explored the association between right-to-left shunt (RLS) and WMLs.MethodsIn this study, we included 998 migraine patients. Contrast transcranial doppler (c-TCD) was used to diagnose RLS and assess the extent of the shunt in RLS patients. Of the 998 patients, 505 underwent cranial magnetic resonance imaging (MRI) assessments. WMLs were classified into periventricular white matter lesions (pvWMLs) and deep white matter lesions (dWMLs).ResultsAmong the 998 migraine patients, 946 had migraine without aura (MO; mean age 36.68 ± 10.46 years; 80.5% female), and 52 had migraine with aura (MA; mean age 29.85 ± 8.59 years; 71.2% female). Compared with MO patients, MA patients had an earlier onset age (23.1 ± 7.97 vs. 28.44 ± 10.38 years, p

Abscisic acid (ABA) significantly regulates plant growth and development, promoting tuberous root formation in various plants. However, the molecular mechanisms of ABA in the tuberous root development of Pseudostellaria heterophylla are not yet fully understood. This study utilized Illumina sequencing and de novo assembly strategies to obtain a reference transcriptome associated with ABA treatment. Subsequently, integrated transcriptomic and proteomic analyses were used to determine gene expression profiles in P. heterophylla tuberous roots. ABA treatment significantly increases the diameter and shortens the length of tuberous roots. Clustering analysis identified 2,256 differentially expressed genes and 679 differentially abundant proteins regulated by ABA. Gene co-expression and protein interaction networks revealed ABA positively induced 30 vital regulators. Furthermore, we identified and assigned putative functions to transcription factors (PhMYB10, PhbZIP2, PhbZIP, PhSBP) that mediate ABA signaling involved in the regulation of tuberous root development, including those related to cell wall metabolism, cell division, starch synthesis, hormone metabolism. Our findings provide valuable insights into the complex signaling networks of tuberous root development modulated by ABA. It provided potential targets for genetic manipulation to improve the yield and quality of P. heterophylla, which could significantly impact its cultivation and medicinal value.

Abstract In recent years, advancements in imaging technologies have led to an increased detection rate of adrenal incidentalomas (AI), with age demonstrating a significant correlation with their incidence. Among the various forms of functional adrenal incidentalomas, subclinical hypercortisolism (SH) stands out as a predominant subtype. Despite the absence of typical symptoms associated with Cushing's syndrome, both domestic and international research consistently establishes a robust link between SH and diverse metabolic irregularities, including hypertension, lipid metabolism disorders, glucose metabolism abnormalities, and disruptions in bone metabolism. Individuals with SH face an elevated risk of cardiovascular events and mortality, highlighting the clinical significance of addressing this condition. Prolonged exposure to elevated cortisol levels poses a significant threat to bone health, contributing to bone loss, alterations in bone microstructure, and an increased susceptibility to fractures. However, comprehensive reviews addressing bone metabolism changes and associated mechanisms in SH patients are currently lacking. Furthermore, the profound impact of concurrent SH on the overall health of the elderly cannot be overstated. A comprehensive understanding of the skeletal health status in elderly individuals with concomitant SH is imperative. This article aims to fill this gap by offering a detailed review of bone metabolism changes and associated mechanisms in SH patients arising from AI. Additionally, it provides a forward‐looking perspective on research concerning skeletal health in elderly individuals with concurrent SH.

This paper provides a Self-adjustment Interval Type II Neural Network (SAIT2NN) method combined with Super-Twisting sliding mode control (STSMC), aiming at solving the harmonic current problem and improving power quality in an active power filter (APF) system. The designed neural network takes the advantages of the interval type II fuzzy system to improve the learning ability for complex object, thereby dealing with the nonlinear changes caused by the APF system well. At the same time, the neural network adopts a signal classification and selecting mechanism to raise learning speed while minimizing signal loss to ensure correctness. The eigenvalues used to evaluate the fuzzed signal are also part of the system signal, ensuring functionality and reducing structural complexity. In order to achieve a theoretically tight fit, the online learning algorithms of the SAIT2NN are developed from the Lyapunov method. In order to make up for the chattering problem caused by the inherent error of the neural network and delay of the system, STSMC is used as a compensation mechanism to further improve the accuracy. Experimental study and comparisons are provided to prove the effectiveness and superiority of the performance.

Abstract Background Bladder cancer is very common worldwide. PIGT is a subunit of the glycosylphosphatidylinositol transamidase which involves in tumorigenesis and invasiveness. m6A modification of mRNA has been linked to cell proliferation, tumor progression and other biological events. However, how PIGT is regulated and what is the function of PIGT in bladder cancer remains to be elucidated. Methods PIGT was silenced or overexpressed to study its role in regulating bladder cancer. Cell proliferation and invasion were examined with the Cell Counting Kit-8, colony formation and Transwell assay, respectively. Cellular oxygen consumption rates or extracellular acidification rates were detected by a XF24 Analyzer. Quantitative RT-PCR and immunoblots were performed to detect mRNA and protein levels. Results PIGT was overexpressed in bladder cancer. Silencing PIGT inhibited cell proliferation, oxidative phosphorylation, and glycolysis. Overexpressing PIGT promoted cell proliferation, oxidative phosphorylation, glycolysis in vitro and tumor metastasis in vivo by activating glucose transporter 1 (GLUT1). PIGT also promoted GLUT1 glycosylation and membrane trafficking. Wilms’ tumor 1-associated protein (WTAP) mediated PIGT m6A modification, and m6A reader, insulin-like growth factor 2 mRNA-binding protein (IGF2BP2), binds to the methylated PIGT to promote the stability of PIGT, leading to up-regulation of PIGT. Conclusion WTAP mediates PIGT m6A modification to increase the stability of PIGT via the IGF2BP2, which enhances cell proliferation, glycolysis, and metastasis in bladder cancer by modulating GLUT1 glycosylation and membrane trafficking.

Abstract Background Angelica sinensis (Danggui), a renowned medicinal orchid, has gained significant recognition for its therapeutic effects in treating a wide range of ailments. Genome information serves as a valuable resource, enabling researchers to gain a deeper understanding of gene function. In recent times, the availability of chromosome-level genomes for A. sinensis has opened up vast opportunities for exploring gene functionality. Integrating multiomics data can allow researchers to unravel the intricate mechanisms underlying gene function in A. sinensis and further enhance our knowledge of its medicinal properties. Results In this study, we utilized genomic and transcriptomic data to construct a coexpression network for A. sinensis. To annotate genes, we aligned them with sequences from various databases, such as the NR, TAIR, trEMBL, UniProt, and SwissProt databases. For GO and KEGG annotations, we employed InterProScan and GhostKOALA software. Additionally, gene families were predicted using iTAK, HMMER, OrholoFinder, and KEGG annotation. To facilitate gene functional analysis in A. sinensis, we developed a comprehensive platform that integrates genomic and transcriptomic data with processed functional annotations. The platform includes several tools, such as BLAST, GSEA, Heatmap, JBrowse, and Sequence Extraction. This integrated resource and approach will enable researchers to explore the functional aspects of genes in A. sinensis more effectively. Conclusion We developed a platform, named ASAP, to facilitate gene functional analysis in A. sinensis. ASAP ( www.gzybioinformatics.cn/ASAP ) offers a comprehensive collection of genome data, transcriptome resources, and analysis tools. This platform serves as a valuable resource for researchers conducting gene functional research in their projects, providing them with the necessary data and tools to enhance their studies.

Abstract Hepatic insulin resistance is central to the metabolic syndrome. Here we investigate the role of BTB and CNC homology 1 (BACH1) in hepatic insulin signaling. BACH1 is elevated in the hepatocytes of individuals with obesity and patients with non-alcoholic fatty liver disease (NAFLD). Hepatocyte-specific Bach1 deletion in male mice on a high-fat diet (HFD) ameliorates hyperglycemia and insulin resistance, improves glucose homeostasis, and protects against steatosis, whereas hepatic overexpression of Bach1 in male mice leads to the opposite phenotype. BACH1 directly interacts with the protein-tyrosine phosphatase 1B (PTP1B) and the insulin receptor β (IR-β), and loss of BACH1 reduces the interaction between PTP1B and IR-β upon insulin stimulation and enhances insulin signaling in hepatocytes. Inhibition of PTP1B significantly attenuates BACH1-mediated suppression of insulin signaling in HFD-fed male mice. Hepatic BACH1 knockdown ameliorates hyperglycemia and improves insulin sensitivity in diabetic male mice. These results demonstrate a critical function for hepatic BACH1 in the regulation of insulin signaling and glucose homeostasis.

Abstract Orthotopic advanced hepatic tumor resection without precise location and preoperative downstaging may cause clinical postoperative recurrence and metastasis. Early accurate monitoring and tumor size reduction based on the multifunctional diagnostic-therapeutic integration platform could improve real-time imaging-guided resection efficacy. Here, a Near-Infrared II/Photoacoustic Imaging/Magnetic Resonance Imaging (NIR-II/PAI/MRI) organic nanoplatform IRFEP-FA-DOTA-Gd (IFDG) is developed for integrated diagnosis and treatment of orthotopic hepatic tumor. The IFDG is designed rationally based on the core “S-D-A-D-S” NIR-II probe IRFEP modified with folic acid (FA) for active tumor targeting and Gd-DOTA agent for MR imaging. The IFDG exhibits several advantages, including efficient tumor tissue accumulation, good tumor margin imaging effect, and excellent photothermal conversion effect. Therefore, the IFDG could realize accurate long-term monitoring and photothermal therapy non-invasively of the hepatic tumor to reduce its size. Next, the complete resection of the hepatic tumor in situ lesions could be realized by the intraoperative real-time NIR-II imaging guidance. Notably, the preoperative downstaging strategy is confirmed to lower the postoperative recurrence rate of the liver cancer patients under middle and advanced stage effectively with fewer side effects. Overall, the designed nanoplatform demonstrates great potential as a diagnostic-therapeutic integration platform for precise imaging-guided surgical navigation of orthotopic hepatic tumors with a low recurrence rate after surgery, providing a paradigm for diagnosing and treating the advanced tumors in the future clinical translation application. Graphical Abstract

Abstract Aims To investigate the effect of Self‐designed Metabolic Equivalent Exercises (SMEE) on cancer‐related fatigue in patients with gastric cancer. Methods 130 patients with gastric cancer admitted to Department of Oncology of a tertiary hospital in Shanghai were enrolled and assessed for eligibility. After excluding 1 patient who declined to participate, 129 eligible patients were randomly assigned into SMEE (n = 65) and control (n = 64) groups. The Revised Piper Fatigue Scale (RPFS) and EORTC QLQ‐C30 Quality of Life Scale were used to measure cancer‐caused fatigue and quality of life, respectively, in both groups at the first admission and after 3 months. Results After excluding patients who did not receive allocated intervention due to medical (n = 3) and personal (n = 2) reasons, those who were lost to follow‐up (n = 3), and those who had discontinued intervention (n = 2), 119 patients (64 in the SMEE group and 55 in the control group) were included for analysis. There were no statistically significant differences in the RPFS or QLQ‐C30 score between the two groups at baseline. After 3 months, the total RPFS score of the SMEE group was significantly lower than that of the control group (2.86 ± 1.75 vs. 4.65 ± 1.29, p = 0.009), with significant improvements in affective meaning (0.83 ± 0.92 vs. 1.13 ± 0.77, p = 0.044) and sensory (0.70 ± 0.71 vs. 1.00 ± 0.54, p

BackgroundResident physicians at the standardized training stage had undergone significant physical and mental stress during the release of the COVID-19 pandemic restrictions at the end of 2022 in China. This study aimed to investigate the psychological status (including anxiety, depression, somatic symptoms, job burnout, and vicarious trauma) of resident physicians and identify its influencing factors under these special periods.MethodsSurvey was conducted one month after the release of the COVID-19 pandemic restrictions on resident training physicians from a tertiary first-class hospital in Zhejiang, China. Resident physicians completed the psychological status questionnaire. Chi-square tests, Mann–Whitney U tests, and logistic regression analyses were used to estimate the group differences and variable associations.ResultsThe prevalence of anxiety, depression, and somatic discomfort in this study was 20.88, 28.53, and 41.47%, respectively. Female resident physicians were more likely to experience somatic symptoms [adjusted odds ratio (OR) = 2.36, 95% confidence interval (CI): 1.33–4.18]. Resident physicians with problem-focused coping styles were less prone to psychological health issues [depression (adjusted OR = 0.92, 95% CI: 0.88–0.96), anxiety (adjusted OR = 0.94, 95% CI: 0.90–0.98), somatic symptoms (adjusted OR = 0.93, 95% CI: 0.89–0.97), job burnout (adjusted OR = 0.91, 95% CI: 0.87–0.96) and vicarious trauma (adjusted OR = 0.94, 95% CI: 0.90–0.98)]. Inversely, resident physicians with emotion-focused coping styles and experienced negative life events were more prone to psychological health issues.ConclusionResident training physicians had a high risk of anxiety, depression, and somatic symptoms under the special COVID-19 pandemic restriction release period. Females, with lower training stages, degrees, negative life events, and emotion-focused coping styles had a disadvantaged effect on psychological status. The medical teaching management department needs to monitor and reduce the workload and working hours of resident physicians, ensure sufficient sleep time, and pay attention to the psychological status of resident physicians. By strengthening regular communication and mental health education or intervention, which can help them improve their ability to cope with complex tasks.

Abstract Controlled assembly of nanoparticles (NPs) has garnered much interest over the past two decades. Beyond established techniques, new methods utilizing local short‐range or large‐scale long‐range interactions remain to be explored to achieve diverse micro‐ and nanoscale structures. Here, we report the controlled emergence of vortex‐pair arrays within monodispersed gold nanorods by applying a direct current electric field across a pair of sawtooth electrodes. By employing in situ darkfield microscopy and particle collective analysis, we elucidate the mechanism behind the formation and stabilization of the NP vortices, attributing it to the combined effects of the electrode shape, high NP density, and high solution viscosity. We further explore the controllability of the vortex‐pair arrays and obtain multiple complex vortice patterns. Our findings will facilitate the investigation of efficient and controlled dynamic assembly of NPs under external fields and help manufacture next‐generation optoelectronic functional materials.

Abstract Background To study the validity of an artificial intelligence (AI) model for measuring fetal facial profile markers, and to evaluate the clinical value of the AI model for identifying fetal abnormalities during the first trimester. Methods This retrospective study used two-dimensional mid-sagittal fetal profile images taken during singleton pregnancies at 11–13+ 6 weeks of gestation. We measured the facial profile markers, including inferior facial angle (IFA), maxilla-nasion-mandible (MNM) angle, facial-maxillary angle (FMA), frontal space (FS) distance, and profile line (PL) distance using AI and manual measurements. Semantic segmentation and landmark localization were used to develop an AI model to measure the selected markers and evaluate the diagnostic value for fetal abnormalities. The consistency between AI and manual measurements was compared using intraclass correlation coefficients (ICC). The diagnostic value of facial markers measured using the AI model during fetal abnormality screening was evaluated using receiver operating characteristic (ROC) curves. Results A total of 2372 normal fetuses and 37 with abnormalities were observed, including 18 with trisomy 21, 7 with trisomy 18, and 12 with CLP. Among them, 1872 normal fetuses were used for AI model training and validation, and the remaining 500 normal fetuses and all fetuses with abnormalities were used for clinical testing. The ICCs (95%CI) of the IFA, MNM angle, FMA, FS distance, and PL distance between the AI and manual measurement for the 500 normal fetuses were 0.812 (0.780–0.840), 0.760 (0.720–0.795), 0.766 (0.727-0.800), 0.807 (0.775–0.836), and 0.798 (0.764–0.828), respectively. IFA clinically significantly identified trisomy 21 and trisomy 18, with areas under the ROC curve (AUC) of 0.686 (95%CI, 0.585–0.788) and 0.729 (95%CI, 0.621–0.837), respectively. FMA effectively predicted trisomy 18, with an AUC of 0.904 (95%CI, 0.842–0.966). MNM angle and FS distance exhibited good predictive value in CLP, with AUCs of 0.738 (95%CI, 0.573–0.902) and 0.677 (95%CI, 0.494–0.859), respectively. Conclusions The consistency of fetal facial profile marker measurements between the AI and manual measurement was good during the first trimester. The AI model is a convenient and effective tool for the early screen for fetal trisomy 21, trisomy 18, and CLP, which can be generalized to first-trimester scanning (FTS).

Abstract Pancreatic cancer (PC) is one of the most common malignancies. Surgical resection is a potential curative approach for PC, but most patients are unsuitable for operations when at the time of diagnosis. Even with surgery, some patients may still experience tumour metastasis during the operation or shortly after surgery, as precise prognosis evaluation is not always possible. If patients miss the opportunity for surgery and resort to chemotherapy, they may face the challenging issue of chemotherapy resistance. In recent years, liquid biopsy has shown promising prospects in disease diagnosis, treatment monitoring, and prognosis assessment. As a noninvasive detection method, liquid biopsy offers advantages over traditional diagnostic procedures, such as tissue biopsy, in terms of both cost-effectiveness and convenience. The information provided by liquid biopsy helps clinical practitioners understand the molecular mechanisms underlying tumour occurrence and development, enabling the formulation of more precise and personalized treatment decisions for each patient. This review introduces molecular biomarkers and detection methods in liquid biopsy for PC, including circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), noncoding RNAs (ncRNAs), and extracellular vesicles (EVs) or exosomes. Additionally, we summarize the applications of liquid biopsy in the early diagnosis, treatment response, resistance assessment, and prognostic evaluation of PC.

A variety of factors cause a reduction in remote sensing image resolution. Unlike super-resolution (SR) reconstruction methods with single degradation assumption, multi-degradation SR methods aim to learn the degradation kernel from low-resolution (LR) images and reconstruct high-resolution (HR) images more suitable for restoring the resolution of remote sensing images. However, existing multi-degradation SR methods only utilize the given LR images to learn the representation of the degradation kernel. The mismatches between the estimated degradation kernel and the real-world degradation kernel lead to a significant deterioration in performance of these methods. To address this issue, we design a reconstruction features-guided kernel correction SR network (RFKCNext) for multi-degradation SR reconstruction of remote sensing images. Specifically, the proposed network not only utilizes LR images to extract degradation kernel information but also employs features from SR images to correct the estimated degradation kernel, thereby enhancing the accuracy. RFKCNext utilizes the ConvNext Block (CNB) for global feature modeling. It employs CNB as fundamental units to construct the SR reconstruction subnetwork module (SRConvNext) and the reconstruction features-guided kernel correction network (RFGKCorrector). The SRConvNext reconstructs SR images based on the estimated degradation kernel. The RFGKCorrector corrects the estimated degradation kernel by reconstruction features from the generated SR images. The two networks iterate alternately, forming an end-to-end trainable network. More importantly, the SRConvNext utilizes the degradation kernel estimated by the RFGKCorrection for reconstruction, allowing the SRConvNext to perform well even if the degradation kernel deviates from the real-world scenario. In experimental terms, three levels of noise and five Gaussian blur kernels are considered on the NWPU-RESISC45 remote sensing image dataset for synthesizing degraded remote sensing images to train and test. Compared to existing super-resolution methods, the experimental results demonstrate that our proposed approach achieves significant reconstruction advantages in both quantitative and qualitative evaluations. Additionally, the UCMERCED remote sensing dataset and the real-world remote sensing image dataset provided by the “Tianzhi Cup” Artificial Intelligence Challenge are utilized for further testing. Extensive experiments show that our method delivers more visually plausible results, demonstrating the potential of real-world application.

Yellow fever virus (YFV) infections can cause severe diseases in humans, resulting in mass casualties in Africa and the Americas each year. Secretory NS1 (sNS1) is thought to be used as a diagnostic marker of flavivirus infections, playing an essential role in the flavivirus life cycle, but little is known about the composition and structure of YFV sNS1. Here, we present that the recombinant YFV sNS1 exists in a heterogeneous mixture of oligomerizations, predominantly in the tetrameric form. The cryoEM structures show that the YFV tetramer of sNS1 is stacked by the hydrophobic interaction between β-roll domains and greasy fingers. According to the 3D variability analysis, the tetramer is in a semi-stable state that may contain multiple conformations with dynamic changes. We believe that our study provides critical insights into the oligomerization of NS1 and will aid the development of NS1-based diagnoses and therapies.

Abstract Background and aims To assess the cost-effectiveness of utilizing IDegLira in comparison to other treatment regimens ( liraglutide and degludec) in managing type 2 diabetes, taking into account the Chinese healthcare system’s perspective. Methods The clinical data were obtained from the randomized controlled trials (RCTs) of the DUAL I and DUAL II evidence studies that took place in China. To estimate the lifetime quality-adjusted life-years (QALYs) and direct medical costs of patients receiving different treatment strategies from a long-term perspective, the IQVIA CORE Diabetes Model version 9.0 (IQVIA, Basel, Switzerland) was utilized. The costs were evaluated from the perspective of the China National Health System. Future costs and clinical benefits were discounted annually at 5%, and sensitivity analyses were conducted. Results IDegLira was projected to reduce the incidence of diabetes-related complications and improve quality-adjusted life expectancy (QALE) versus liraglutide and degludec. A survival benefit was observed with IDegLira over Liraglutide (0.073 years). Lifetime costs were lower by Chinese yuan (CNY) 27,945 on IDegLira than on Liraglutide therapy. A similar survival benefit was observed with IDegLira over degludec (0.068 years). Lifetime costs were lower by CNY 1196 on IDegLira than on degludec therapy. Therefore, IDegLira was found to be cost-effective versus liraglutide and degludec with incremental cost-effectiveness ratios of Dominant per QALY gained, respectively, under the threshold of three times the gross domestic product (GDP) per capita in China. Conclusion IDegLira is a cost-effective hypoglycemic treatment option that delivers positive clinical outcomes while also reducing costs for Chinese patients living with type 2 diabetes.

Abstract Background Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. Methods A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. Results Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44–1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21–1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08–5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33–0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36–0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. Conclusions The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. Trial registration Chictr.org.cn identifier: ChiCTR-SOC-17010976.

Abstract Asian citrus psyllid (Diaphorina citri, D. citri) is the important vector of “Candidatus Liberibacter asiaticus” (CLas), associated with Huanglongbing, the most devastating citrus disease worldwide. CLas can affect endosymbiont abundance of D. citri. Here, we generated the high-quality gut endosymbiont metagenomes of Diaphorina citri on the condition of CLas infected and uninfected. The dataset comprised 6616.74 M and 6586.04 M raw reads, on overage, from CLas uninfected and infected psyllid strains, respectively. Taxonomic analysis revealed that a total of 1046 species were annotated with 10 Archaea, 733 Bacteria, 234 Eukaryota, and 69 Viruses. 80 unique genera in CLas infected D. citri were identified. DIAMOND software was used for complement function research against various functional databases, including Nr, KEGG, eggNOG, and CAZy, which annotated 84543 protein-coding genes. These datasets provided an avenue for further study of the interaction mechanism between CLas and D. citri.

CpG oligodeoxynucleotides (CpG ODNs) boost the humoral and cellular immune responses to antigens through interaction with Toll-like receptor 9 (TLR9). These CpG ODNs have been extensively utilized in human vaccines. In our study, we evaluated five B-type CpG ODNs that have stimulatory effects on pigs by measuring the proliferation of porcine peripheral blood mononuclear cells (PBMCs) and assessing interferon gamma (IFN-γ) secretion. Furthermore, this study examined the immunoenhancing effects of the MF59 and CpG ODNs compound adjuvant in mouse and piglet models of porcine epidemic diarrhea virus (PEDV) subunit vaccine administration. The in vitro screening revealed that the CpG ODN named CpG5 significantly stimulated the proliferation of porcine PBMCs and elevated IFN-γ secretion levels. In the mouse vaccination model, CpG5 compound adjuvant significantly bolstered the humoral and cellular immune responses to the PEDV subunit vaccines, leading to Th1 immune responses characterized by increased IFN-γ and IgG2a levels. In piglets, the neutralizing antibody titer was significantly enhanced with CpG5 compound adjuvant, alongside a considerable increase in CD8+ T lymphocytes proportion. The combination of MF59 adjuvant and CpG5 exhibits a synergistic effect, resulting in an earlier, more intense, and long-lasting immune response in subunit vaccines for PEDV. This combination holds significant promise as a robust candidate for the development of vaccine adjuvant.

Summary: The role of BACH1 in the process of vascular smooth muscle cell (VSMC) differentiation from human embryonic stem cells (hESCs) remains unknown. Here, we find that the loss of BACH1 in hESCs attenuates the expression of VSMC marker genes, whereas overexpression of BACH1 after mesoderm induction increases the expression of VSMC markers during in vitro hESC-VSMC differentiation. Mechanistically, BACH1 binds directly to coactivator-associated arginine methyltransferase 1 (CARM1) during in vitro hESC-VSMC differentiation, and this interaction is mediated by the BACH1 bZIP domain. BACH1 recruits CARM1 to VSMC marker gene promoters and promotes VSMC marker expression by increasing H3R17me2 modification, thus facilitating in vitro VSMC differentiation from hESCs after the mesoderm induction. The increased expression of VSMC marker genes by BACH1 overexpression is partially abolished by inhibition of CARM1 or the H3R17me2 inhibitor TBBD in hESC-derived cells. These findings highlight the critical role of BACH1 in hESC differentiation into VSMCs by CARM1-mediated methylation of H3R17.

The bottom interface between perovskite and electron-transporting layer is critical for realizing efficient flexible perovskite solar cells. Here, the authors intercalate liquid crystal elastomer interlayer for aligned mesogenic assembly and achieve maximum efficiency of 23.26% with T 80 over 1570 h.

Abstract Background Familial hypercholesterolemia (FH) is an inherited metabolic disorder with a high level of low-density lipoprotein cholesterol and the worse prognosis. The triglyceride-glucose (TyG) index, an emerging tool to reflect insulin resistance (IR), is positively associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) in healthy individuals, but the value of TyG index has never been evaluated in FH patients. This study aimed to determine the association between the TyG index and glucose metabolic indicators, insulin resistance (IR) status, the risk of ASCVD and mortality among FH patients. Methods Data from National Health and Nutrition Examination Survey (NHANES) 1999–2018 were utilized. 941 FH individuals with TyG index information were included and categorized into three groups: 9.0. Spearman correlation analysis was used to test the association of TyG index and various established glucose metabolism-related indicators. Logistic and Cox regression analysis were used to assess the association of TyG index with ASCVD and mortality. The possible nonlinear relationships between TyG index and the all-cause or cardiovascular death were further evaluated on a continuous scale with restricted cubic spline (RCS) curves. Results TyG index was positively associated with fasting glucose, HbA1c, fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) index (all p

Abstract Background The current molecular classifications cannot completely explain the polarized malignant biological behavior of low‐grade gliomas (LGGs), especially for tumor recurrence. Therefore, we tried to identify suspicious hub genes related to tumor recurrence in LGGs. Methods In this study, we constructed a gene‐miRNA‐lncRNA co‐expression network for LGGs by a weighted gene co‐expression network analysis (WGCNA). GDCRNATools and the WGCNA R package were mainly used in data analysis. Results Sequencing data from 502 LGG patients were analyzed in this study. Compared with recurrent glioma tissues, we identified 774 differentially expressed (DE) mRNAs, 49 DE miRNAs, and 129 DE lncRNAs in primary LGGs and ultimately determined that the expression of MKLN1 was related to tumor recurrence in LGG. Conclusion This study identified the potential biomarkers for the pathogenesis and recurrence of LGGs and proposed that MKLN1 could be a potential therapeutic target.

Abstract Histopathology plays a great role in diagnosing various diseases, which is considered as a golden standard for tumor identification. The tissue constituents must be stained by visible labels for microscopic analysis by medical experts. However, this process is time‐consuming, labor‐intensive, and expensive, which requires rapid pathological approaches for diagnosis in the operating room. Here, we present an easy‐to‐process and high‐performance perovskite biological probes for rapid and visual pathological diagnosis of glioma. Perovskite quantum dots can be encapsulated by the copolymer into nanocrystals (PNCs) with a diameter of 100 nm, which is modified with chlorotoxin to achieve the specific recognition of glioma. Benefiting from the super photoluminescence quantum yield (above 93%) of EVA@PNCs aqueous solution, the glioma can be clearly imaged and captured via a smartphone under the excitation of a handheld UV lamp. To demonstrate the visualization and efficiency of PNC probes, different malignant grades of brain tumor sections can be distinguished in no more than 5 min. This strategy provides a general auxiliary diagnosis platform for achieving the histopathology analysis near the operating bed, which is currently not feasible with standard histochemical staining methods.

Small nucleolar RNA host gene 15 (SNHG15) plays an oncogenic role in many cancers. However, the role of SNHG15 in bladder cancer (BLCA) remains unclear. In this study, the regulation of SNHG15 on the activities of BLCA cells (T24 and RT112) was investigated. In detail, super-enhancers (SEs), differentially expressed genes, and functional enrichment were detected by bioinformatic analyses. Mutant cell lines lacking SNHG15-SEs were established using CRISPR-Cas9. Relative gene expression was detected by quantitative polymerase chain reaction (qPCR), western blot, in situ hybridization, and immunohistochemistry assays. Cell senescence, apoptosis, viability, and proliferation were measured. Chromatin immunoprecipitation (ChIP)-qPCR and luciferase reporter gene assays were conducted to analyze the interactions between genes. A novel super-enhancer of SNHG15 (SNHG15-SEs) was discovered in several BLCA datasets. The deletion of SNHG15-SEs resulted in a significant downregulation of SNHG15. Mechanistically, the core active region of SNHG15-SEs recruited the transcription factor FOSL1 to facilitate the SNHG15 transcription, thereby inducing the proliferation and metastasis of BLCA cells. Deletion of SNHG15-SEs inhibited the growth and metastasis of T24 and RT112 cells by inactivating the WNT/CTNNB1 pathway activation. Overexpression of FOSL1 in SNHG15-SEs restored the cell proliferation and metastasis. Next, a xenograft mouse model showed that SNHG15-SEs deletion inhibited the proliferation and metastasis of BLCA cells in vivo. Collectively, our data indicate that SNHG15-SEs recruit FOSL1 to promote the expression of SNHG15 which interacts with CTNNB1 in the nucleus to activate the transcription of ADAM12, leading to the malignance of BLCA cells.

Abstract Studies in recent years have highlighted an elaborate crosstalk between T cells and bone cells, suggesting that T cells may be alternative therapeutic targets for the maintenance of bone homeostasis. Here, it is reported that systemic administration of low‐dose staphylococcal enterotoxin C2 (SEC2) 2M‐118, a form of mutant superantigen, dramatically alleviates ovariectomy (OVX)‐induced bone loss via modulating T cells. Specially, SEC2 2M‐118 treatment increases trabecular bone mass significantly via promoting bone formation in OVX mice. These beneficial effects are largely diminished in T‐cell‐deficient nude mice and can be rescued by T‐cell reconstruction. Neutralizing assays determine interferon gamma (IFN‐γ) as the key factor that mediates the beneficial effects of SEC2 2M‐118 on bone. Mechanistic studies demonstrate that IFN‐γ stimulates Janus kinase/signal transducer and activator of transcription (JAK–STAT) signaling, leading to enhanced production of nitric oxide, which further activates p38 mitogen‐activated protein kinase (MAPK) and Runt‐related transcription factor 2 (Runx2) signaling and promotes osteogenic differentiation. IFN‐γ also directly inhibits osteoclast differentiation, but this effect is counteracted by proabsorptive factors tumor necrosis factor alpha (TNF‐α) and interleukin 1 beta (IL‐1β) secreted from IFN‐γ‐stimulated macrophages. Taken together, this work provides clues for developing innovative approaches which target T cells for the prevention and treatment of osteoporosis.

Abstract The increasing burden of heart failure with preserved ejection fraction (HFpEF) has become a global health problem. HFpEF is characterized by systematic inflammation, cardiac metabolic remodeling, and fibrosis. Eosinophils act as an essential but generally overlooked subgroup of white blood cells, which participate in cardiac fibrosis, as reported in several recent studies. Herein, we explored the role of eosinophils in a “two‐hit” preclinical HFpEF model. The peripheral eosinophil counts were comparable between the normal chow and HFpEF mice. Deficiency of eosinophils failed to alter the phenotype of HFpEF. Conclusively, the development of HFpEF is independent of eosinophils in terms of the functional, biochemical, and histological results.

ObjectiveTo explore physical shape changes in preschool children from 2000 to 2020, and forecast development trends over the next 10 years.MethodThe grey GM (1,1) prediction model was used to fit the physical shape indicators of preschool children in China from 2000 to 2020, and then the longitudinal change trend of physical shape was compared and analyzed. Finally, the development trend of physical shape in China in 2025 and 2030 was predicted.Results(1) During the period from 2000 to 2020, the height, weight and chest circumference of Chinese preschool children all increased rapidly. Specifically, the weight of male and female children increased by 1.8 kg and 1.6 kg, their chest circumference increased by 1.6 cm and 1.5 cm, respectively, and both their heights increased by 3.6 cm. Among these indicators, the older the age, the greater the growth rate. It is expected that all the indicators will continue to grow rapidly over the next 10 years, but the growth rate will slow. (2) From 2000 to 2020, the growth rate of weight was higher than that of height, and BMI showed an increasing trend. The obesity detection rates in boys and girls increased by 5.6 and 2.8%, respectively. Over the next 10 years, the incidence of obesity is expected to increase by 3.8% in boys and 2.8% in girls. (3) Improvement in the growth and development of preschool children in China has a certain correlation with the rapid growth of China’s economy,less physical activity, education and other factors.ConclusionOver the past 20 years, the growth and nutritional status of Chinese preschoolers have improved dramatically, but overweight and obesity remain. Overweight and obesity rates are expected to continue to increase rapidly over the next 10 years, particularly among boys, and effective measures should be taken to control the obesity epidemic.

Abstract To evaluate the suitability of silica‐reinforced silicone foam materials under extreme conditions, we studied the coupling effect of silica‐reinforced silicone foam material in irradiation and corrosive solution environment. The results showed that irradiation at 5 wt% KMnO4 attenuated the increase in crosslink density of silicone foams, while a different observation was found when the samples were treated with a 5 wt% HNO3 solution. The HNO3‐treated samples showed a significant decrease in elongation at break compared to the untreated samples. Mechanical properties, swelling, TGA, SEM, and XPS showed that HNO3 had a severe effect on the structure of the silicone foam. This may be due to the fact that the highly corrosive HNO3 disrupts the connecting structure between the silicone foam matrix and the filler. Based on this analysis, the damage mechanism of silicon foam material under the coupling conditions of corrosive solution and irradiation was proposed.

The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC50 values and significant selectivity towards other S-adenosyl-L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC50 value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour.

Abstract Background As a cardiometabolic disease, hypertension has shown an obvious upward trend, becoming a global epidemic chronic disease. Lifestyle intervention is a fundamental method for lowering blood pressure. This systematic review and meta-analysis aimed to evaluate the effects of time-restricted eating (TRE) on blood pressure. Methods Studies were retrieved from the PubMed, Embase, Cochrane Library, and Web of Science databases to evaluate the effects of TRE on blood pressure. The time frame of search was from the start of database construction until July 14, 2022.There were no language restrictions. Meta-analysis and meta-regression were performed using Stata version 16. The weighted mean difference with 95% CI was used to assess the effect of TRE on blood pressure, heart rate, weight, blood glucose, total cholesterol, HDL-C, LDL-C, and triglycerides. The main ending of this article were blood pressure and heart rate, while the secondary ending were weight, blood glucose, total cholesterol, HDL-C, LDL-C, and triglycerides. Results Ten randomized controlled trials involving 694 patients were identified. TRE significantly reduced systolic blood pressure (SBP) (mean difference = −4.15; 95% CI: −6.73, −2.30; P < 0.0001), but had no significant effect on diastolic blood pressure (DBP) (mean difference = −2.06; 95% CI: −4.16, 0.02; P = 0.053) and no beneficial effect on heart rate (mean difference = 0.36; 95% CI: −2.83, 3.54; P = 0.0825). TRE promoted weight loss (mean difference = −1.63; 95% CI: −2.61, −0.64; P = 0.001) and decreased blood glucose levels (mean difference = −2.80; 95% CI: −4.64, −0.96; P = 0.003), but had no significant effect on total cholesterol (mean difference = 0.03, 95% CI: −10.01, 10.08; P = 0.995), HDL-C (mean difference = 0.85, 95% CI: −1.80, 3.49; P = 0.531), LDL-C (mean difference = −0.86, 95% CI: −6.47, 4.76; P = 0.764), or triglycerides (mean difference = −3.524, 95% CI: −9.49, 2.45; P = 0.248). In a separate meta-regression analysis, the degree of SBP change was related to weight loss (P = 0.044) but not to glucose improvement (P = 0.867). Conclusions The present meta-analysis suggests that TRE significantly reduced SBP, while no effect of reducing DBP was seen. The observed lower blood pressure may be attributed to significant weight loss. The effects of TRE on heart rate and blood lipid levels were not apparent.

Abstract Long noncoding RNAs (lncRNAs) are usually 5′ capped and 3′ polyadenylated, similar to most typical mRNAs. However, recent studies revealed a type of snoRNA-related lncRNA with unique structures, leading to questions on how they are processed and how they work. Here, we identify a novel snoRNA-related lncRNA named LNC-SNO49AB containing two C/D box snoRNA sequences, SNORD49A and SNORD49B; and show that LNC-SNO49AB represents an unreported type of lncRNA with a 5′-end m7G and a 3′-end snoRNA structure. LNC-SNO49AB was found highly expressed in leukemia patient samples, and silencing LNC-SNO49AB dramatically suppressed leukemia progression in vitro and in vivo. Subcellular location indicated that the LNC-SNO49AB is mainly located in nucleolus and interacted with the nucleolar protein fibrillarin. However, we found that LNC-SNO49AB does not play a role in 2′-O-methylation regulation, a classical function of snoRNA; instead, its snoRNA structure affected the lncRNA stability. We further demonstrated that LNC-SNO49AB could directly bind to the adenosine deaminase acting on RNA 1(ADAR1) and promoted its homodimerization followed by a high RNA A-to-I editing activity. Transcriptome profiling shows that LNC-SNO49AB and ADAR1 knockdown respectively share very similar patterns of RNA modification change in downstream signaling pathways, especially in cell cycle pathways. These findings suggest a previously unknown class of snoRNA-related lncRNAs, which function via a manner in nucleolus independently on snoRNA-guide rRNA modification. This is the first report that a lncRNA regulates genome-wide RNA A-to-I editing by enhancing ADAR1 dimerization to facilitate hematopoietic malignancy, suggesting that LNC-SNO49AB may be a novel target in therapy directed to leukemia.

Abstract Objectives To study the correlations between facial profile markers and crown-lump length (CRL) in a Chinese population, and to evaluate the clinical value of these markers for abnormal fetuses during the first trimester (11 to 13+6 gestational weeks). Methods The facial profile markers were as followings: inferior facial angle (IFA), maxilla-nasion-mandible (MNM) angle, facial maxillary angle (FMA), frontal space (FS) distance and profile line (PL) distance. These markers were measured in facial mid-sagittal section through ViewPoint 6 software. The diagnostic value of these markers for abnormal fetuses was assessed by receiver operating characteristic (ROC) curves. Results According to the first-trimester scanning (FTS) and follow-up, 31 fetuses were enrolled in the abnormal group, including 14 cases of trisomy 21, 7 cases of trisomy 18, 10 cases with cleft lip and palate (CLP), and 1000 normal fetuses were selected. Among the normal fetuses, the IFA, FS distance and PL distance had negative correlations with CRL. The MNM angle and FMA had positive correlations with CRL. The mean IFA values for fetuses with trisomy 21 and trisomy 18 were 74.11° (standard deviation (SD) 7.48) and 69.88° (SD 7.08), respectively, which were significantly smaller than the normal fetuses (p = 0.013; p = 0.003). The mean MNM angle of fetuses with trisomy 18 and CLP were 6.98° (SD 2.61) and 9.41° (SD 2.57), respectively, which were significantly greater than the normal fetuses (p = 0.005; p