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Abstract Background Extensive research has been conducted on embryonic developmental disorders linked to Polycystic Ovary Syndrome (PCOS), a pathological condition that affects 5−10% of women and is characterized by irregularities in the menstrual cycle and infertility. By employing RNA sequencing (RNA-seq), we performed an in-depth investigation of PCOS-related changes in gene expression patterns at the mouse blastocyst stage. Methods The zygotes of female B6D2 mice were obtained and then differentiated into blastocysts in K + Simplex Optimised Medium (KSOM) cultures containing exo-NC (negative control for exosomes) or exo-LIPE-AS1 (a novel exosomal marker of PCOS). Subsequently, blastocysts were collected for RNA-seq. The bioinformatics was performed to analyze and compare the differences of gene expression profile between blastocysts of control and PCOS group. Results There were 1150 differentially expressed genes (DEGs) between the two groups of mouse blastocysts; 243 genes were upregulated and 907 downregulated in the blastocysts of the exo-LIPE-AS1 group compared to those of the exo-NC group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the genes involved in amino acid synthesis and glutathione metabolic pathways were down-regulated in exo-LIPE-AS1 group. Conclusion This study has revealed that blastocyst developmental retardation may be associated with the downregulation of amino acid synthesis and glutathione metabolism, which may affect energy metabolism, biosynthesis, cellular osmotic pressure, antioxidant synthesis, ROS clearance or mitochondrial function, and ultimately cause blastocyst cell development abnormalities. Our research offers encouraging data on the mechanisms underlying aberrant embryonic development in patients with PCOS as well as potential treatment strategies.

Abstract Although aspirin can reduce the incidence of colorectal cancer (CRC), there is still uncertainty about its significance as a treatment for CRC, and the mechanism of aspirin in CRC is not well understood. In this study, we used aspirin to prevent AOM/DSS-induced CRC in mice, and the anti-CRC efficacy of aspirin was assessed using haematoxylin and eosin (H&E) staining and by determining the mouse survival rate and tumour size. 16S rDNA sequencing, flow cytometry (FCM), and Western blotting were also conducted to investigate the changes in the gut microbiota, tumour immune microenvironment, and apoptotic proteins, respectively. The results demonstrated that aspirin significantly exerted anti-CRC effects in mice. According to 16S rDNA sequencing, aspirin regulated the composition of the gut microbiota and dramatically reduced the abundance of Enterococcus cecorum. FCM demonstrated that there were more CD155 tumour cells and CD4 + CD25 + Treg cells showed increased TIGIT levels. Moreover, increased TIGIT expression on Treg cells is associated with reduced Treg cell functionality. Importantly, the inhibition of Treg cells is accompanied by the promotion of CD19 + GL-7 + B cells, CD8 + T cells, CD4 + CCR4 + Th2 cells, and CD4 + CCR6 + Th17 cells. Overall, aspirin prevents colorectal cancer by regulating the abundance of Enterococcus cecorum and TIGIT + Treg cells.

Abstract Background Nigeria is facing a severe malaria crisis, accounting for a significant proportion of global cases and deaths of malaria. This study aimed to investigate the differences between female-headed households (FHHs) and male-headed households (MHHs) and their impact on malaria risk among children under five (U5) in Nigeria. Methods Data from the 2021 Nigeria Malaria Indicator Survey (NMIS) were used for this cross-sectional study. A representative sample of 10,988 households was analysed, with key variables subjected to frequency calculations, descriptive statistics, and bivariate analyses using t-tests and chi-square analyses to compare the differences between FHHs and MHHs. Results Among all participants, 92.1% (N = 10,126) reported residing in male-headed households, while 7.8% (N = 862) reported living in female-headed households. MHHs were significantly more likely to own insecticide-treated bed nets (ITNs) than FHHs (64.7% vs. 53.6%, P

Abstract The AV3Sb5 prototype kagome materials have been demonstrated as a versatile platform for exploring exotic properties in condensed matter physics, including charge density waves, superconductivity, non-trivial electron topology, as well as topological superconductivity. Here we identify that ANb3Bi5 (A = K, Rb, Cs) exhibit non-trivial coexisting superconductivity and topological properties via first-principles calculations. The negative formation energy and the absence of imaginary phonon dispersion demonstrate both thermodynamics and dynamics stabilities of ANb3Bi5 (A = K, Rb, Cs) under ambient conditions. By analytically solving the Allen-Dynes-modified McMillan formula, the superconducting transition temperatures are predicted to be 2.11, 2.15 and 2.21 K for KNb3Bi5, RbNb3Bi5, and CsNb3Bi5, respectively. More importantly, the kagome materials proposed here can be classified into $${{\mathbb{Z}}}_{2}$$ Z 2 topological metals due to the non-trivial topological index and the obvious surface states around the Fermi level. Such coexistence of superconductivity and non-trivial band characters in ANb3Bi5 (A = K, Rb, Cs) offer us more insights to study the relationship between superconductivity and topological properties, and to design innate topological superconductors.

Abstract Background There is growing evidence linking the age-adjusted Charlson comorbidity index (aCCI), an assessment tool for multimorbidity, to fragility fracture and fracture-related postoperative complications. However, the role of multimorbidity in osteoporosis has not yet been thoroughly evaluated. We aimed to investigate the association between aCCI and the risk of osteoporosis in older adults at moderate to high risk of falling. Methods A total of 947 men were included from January 2015 to August 2022 in a hospital in Beijing, China. The aCCI was calculated by counting age and each comorbidity according to their weighted scores, and the participants were stratified into two groups by aCCI: low (aCCI

Abstract Background The primary duodenal gastrointestinal stromal tumor (GIST) is a rare type of gastrointestinal tract tumor. Limited resection (LR) has been increasingly performed for duodenal GIST. However, only a few studies reported minimally invasive limited resection (MI-LR) for primary duodenal GIST. Methods The clinical data of 33 patients with primary duodenal GIST from December 2014 to February 2024 were retrospectively analyzed including 23 who received MI-LR and 10 who received laparoscopic or robotic pancreaticoduodenectomy (LPD/RPD). Results A total of 33 patients with primary duodenal GIST were enrolled and retrospectively reviewed. Patients received MI-LR exhibited less OT (280 vs. 388.5min, P=0.004), EBL (100 vs. 450ml, P

Abstract Background Uterine rupture in pregnant women can lead to serious adverse outcomes. This study aimed to explore the clinical characteristics, treatment, and prognosis of patients with complete uterine rupture. Methods Data from 33 cases of surgically confirmed complete uterine rupture at Chenzhou No.1 People’s Hospital between January 2015 and December 2022 were analyzed retrospectively. Results In total, 31,555 pregnant women delivered in our hospital during the study period. Of these, approximately 1‰ (n = 33) had complete uterine rupture. The average gestational age at complete uterine rupture was 31+4 weeks (13+1–40+3 weeks), and the average bleeding volume was 1896.97 ml (200–6000 ml). Twenty-six patients (78.79%) had undergone more than two deliveries. Twenty-five women (75.76%) experienced uterine rupture after a cesarean section, two (6.06%) after fallopian tube surgery, one (3.03%) after laparoscopic cervical cerclage, and one (3.03%) after wedge resection of the uterine horn, and Fifteen women (45.45%) presented with uterine rupture at the original cesarean section incision scar. Thirteen patients (39.39%) were transferred to our hospital after their initial diagnosis. Seven patients (21.21%) had no obvious symptoms, and only four patients (12.12%) had typical persistent lower abdominal pain. There were 13 cases (39.39%, including eight cases ≥ 28 weeks old) of fetal death in utero and two cases (6.06%, both full term) of severe neonatal asphyxia. The rates of postpartum hemorrhage, blood transfusion, hysterectomy were 66.67%, 63.64%, and 21.21%. Maternal death occurred in one case (3.03%). Conclusions The site of the uterine rupture was random, and was often located at the weakest point of the uterus. There is no effective means for detecting or predicting the weakest point of the uterus. Rapid recognition is key to the treatment of uterine rupture.

Abstract Background Small RNAs are essential for germ cell development and fertilization. However, fundamental questions remain, such as the level of conservation in small RNA composition between species and whether small RNAs control transposable elements in mammalian oocytes. Results Here, we use high-throughput sequencing to profile small RNAs and poly(A)-bearing long RNAs in oocytes of 12 representative vertebrate species (including 11 mammals). The results show that miRNAs are generally expressed in the oocytes of each representative species (although at low levels), whereas endo-siRNAs are specific to mice. Notably, piRNAs are predominant in oocytes of all species (except mice) and vary widely in length. We find PIWIL3-associated piRNAs are widespread in mammals and generally lack 3′-2′-O-methylation. Additionally, sequence identity is low between homologous piRNAs in different species, even among those present in syntenic piRNA clusters. Despite the species-specific divergence, piRNAs retain the capacity to silence younger TE subfamilies in oocytes. Conclusions Collectively, our findings illustrate a high level of diversity in the small RNA populations of mammalian oocytes. Furthermore, we identify sequence features related to conserved roles of small RNAs in silencing TEs, providing a large-scale reference for future in-depth study of small RNA functions in oocytes.

Abstract Background Soybean is a major oil crop; the nutritional components of soybean oil are mainly controlled by unsaturated fatty acids (FA). Unsaturated FAs mainly include oleic acid (OA, 18:1), linoleic acid (LLA, 18:2), and linolenic acid (LNA, 18:3). The genetic architecture of unsaturated FAs in soybean seeds has not been fully elucidated, although many independent studies have been conducted. A 3 V multi-locus random single nucleotide polymorphism (SNP)-effect mixed linear model (3VmrMLM) was established to identify quantitative trait loci (QTLs) and QTL-by-environment interactions (QEIs) for complex traits. Results In this study, 194 soybean accessions with 36,981 SNPs were calculated using the 3VmrMLM model. As a result, 94 quantitative trait nucleotides (QTNs) and 19 QEIs were detected using single-environment (QTN) and multi-environment (QEI) methods. Three significant QEIs, namely rs4633292, rs39216169, and rs14264702, overlapped with a significant single-environment QTN. Conclusions For QTNs and QEIs, further haplotype analysis of candidate genes revealed that the Glyma.03G040400 and Glyma.17G236700 genes were beneficial haplotypes that may be associated with unsaturated FAs. This result provides ideas for the identification of soybean lipid-related genes and provides insights for breeding high oil soybean varieties in the future.

Abstract Glioma is easy to develop resistance to temozolomide (TMZ). TMZ-resistant glioma secretes interleukin-10 (IL-10) and transforming growth factor-β (TGF-β), recruiting regulatory T cell (Treg) and inhibiting the activity of T cells and natural killer cell (NK cell), subsequently forming an immunosuppressive microenvironment. Oxaliplatin (OXA) greatly inhibits the proliferation of TMZ-resistant glioma cells, but the ability of OXA to cross blood–brain barrier (BBB) is weak. Thus, the therapeutic effect of OXA on glioma is not satisfactory. Transferrin receptor 1 (TfR1) is highly expressed in brain capillary endothelial cells and TMZ-resistant glioma cells. In this study, OXA was loaded into ferritin (Fn) to prepare glioma-targeted oxaliplatin/ferritin clathrate OXA@Fn. OXA@Fn efficiently crossed BBB and was actively taken up by TMZ-resistant glioma cells via TfR1. Then, OXA increased the intracellular H2O2 level and induced the apoptosis of TMZ-resistant glioma cells. Meanwhile, Fn increased Fe2+ level in TMZ-resistant glioma cells. In addition, the expression of ferroportin 1 was significantly reduced, resulting in Fe2+ to be locked up inside the TMZ-resistant glioma cells. This subsequently enhanced the Fenton reaction and boosted the ferroptosis of TMZ-resistant glioma cells. Consequently, T cell mediated anti-tumor immune response was strongly induced, and the immunosuppressive microenvironment was significantly reversed in TMZ-resistant glioma tissue. Ultimately, the growth and invasion of TMZ-resistant glioma was inhibited by OXA@Fn. OXA@Fn shows great potential in the treatment of TMZ-resistant glioma and prospect in clinical transformation. Graphical Abstract

The study utilizes a multi-directional compression (MDC) process on a basal-textured ZK60 alloy with the aim of inducing extensive twinning, which is followed by an aging treatment on the pre-deformed sample. The mechanical response and corrosion behavior of the deformed and aged samples are systematically investigated. The MDC process effectively generates numerous {10 1‾ 2} twins with increased compression passes, resulting in the enhanced grain refinement. The interplay between twins and numerous dislocations formed during pre-deformation plays a crucial role in altering both the distribution and morphology of the second phase precipitated during aging. During the aging process, the alloy exhibits a higher concentration of dense rod-like β′ phase and disk-like β″ phase. Remarkably, the compressive yield strength and ultimate strength of aged ZK60 alloy along the rolling direction are significantly improved without obvious compromise of ductility by pre-compression. Notably, the yield strength of the sample after 12-passes compression and aging (APD-12) is approximately 45 % higher than that of the sample without pre-compression (APD-0). Furthermore, the corrosion resistance of ZK60 alloy displays notable improvement upon pre-compression treatment. Specifically, the hydrogen evolution in the APD-12 sample is halved compared to the APD-0 sample. Electrochemical assessments were conducted on both pre-compressed and non-pre-compressed samples, revealing their distinct behaviors. Furthermore, an in-depth exploration has also been undertaken into the underlying mechanisms contributing to the enhancement of mechanical properties and corrosion resistance resulting from the pre-compression.

Background The study aims to evaluate the diagnostic efficacy of contrast-enhanced ultrasound (CEUS) and shear-wave elastography (SWE) in detecting small malignant breast nodules in an effort to inform further refinements of the Breast Imaging Reporting and Data System (BI-RADS) classification system. Methods This study retrospectively analyzed patients with breast nodules who underwent conventional ultrasound, CEUS, and SWE at Gongli Hospital from November 2015 to December 2019. The inclusion criteria were nodules ≤ 2 cm in diameter with pathological outcomes determined by biopsy, no prior treatments, and solid or predominantly solid nodules. The exclusion criteria included pregnancy or lactation and low-quality images. Imaging features were detailed and classified per BI-RADS. Diagnostic accuracy was assessed using receiver operating characteristic curves. Results The study included 302 patients with 305 breast nodules, 113 of which were malignant. The diagnostic accuracy was significantly improved by combining the BI-RADS classification with CEUS and SWE. The combined approach yielded a sensitivity of 88.5%, specificity of 87.0%, positive predictive value of 80.0%, negative predictive value of 92.8%, and accuracy of 87.5% with an area under the curve of 0.877. Notably, 55.8% of BI-RADS 4A nodules were downgraded to BI-RADS 3 and confirmed as benign after pathological examination, suggesting the potential to avoid unnecessary biopsies. Conclusion The integrated use of the BI-RADS classification, CEUS, and SWE enhances the accuracy of differentiating benign and malignant small breast nodule, potentially reducing the need for unnecessary biopsies.

The widespread use and subsequent accumulation of florfenicol (FFC), a common antibiotic, through the food chain poses significant risks to aquatic ecosystems and human health, necessitating effective strategies for its removal from water bodies. To solve the challenge, herein, we developed a novel aluminum-based metal–organic framework CAU-1, engineered for the efficient adsorption of FFC. CAU-1 contains the plentiful –NH2 and μ-OH groups with the positively charged on the surface. In the adsorption process, CAU-1 perform hydrogen bonding interactions with FFC’s functional groups (−F, –OH, −Cl, –NH–, and −SO2–). Furthermore, the positively charged surface of CAU-1 enhances FFC adsorption via electrostatic attraction together. FFC adsorption equilibrium on CAU-1 is attained within 180 min with a monolayer adsorption capacity of 386 mg/g at 303 K, surpassing most of the reported adsorbents. The exothermic FFC adsorption process on CAU-1 remains largely unaffected by coexisting ions. Additionally, CAU-1 can be efficiently regenerated using a mixed solution of 0.1 M HCl and ethanol–water as an eluent. This work highlights CAU-1’s potential as an effective adsorbent for FFC removal, emphasizing the importance of tuning or designing surface functional groups on adsorbents to boost their adsorption capabilities.

Abstract Background Patients with DNA mismatch repair‐proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti‐PD‐1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. Methods In this pilot study, we administered six preoperative doses of each 2‐week cycle of the anti‐PD‐1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5‐FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. Results By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow‐up was 24.7 months (IQR: 21.1–26.1). All patients underwent R0 surgical resection without treatment‐related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence‐free. Treatment‐related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10−8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non‐pCR tumors (p = 0.038 and p = 0.015, respectively). Conclusions Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non‐pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD‐1 blockade‐enhanced targeted chemotherapy require further investigation.

The effects of constant and variable temperature hot-air drying methods on drying time, colors, nutrients, and volatile compounds of three chili pepper varieties were investigated in this study. Overall, the variable temperature drying could facilitate the removal of water, preserve surface color, and reduce the loss of total sugar, total acid, fat and capsaicin contents. Electronic-nose (E-nose) and gas chromatography-ion mobility spectroscopy (GC-IMS) analyses found that aldehydes, ketones, alcohols and esters contributed to the aroma of chili peppers. The drying process led to an increase in acids, furans and sulfides contents, while decreasing alcohols, esters and olefins levels. In addition, the three chili pepper varieties displayed distinct physical characteristics, drying times, chromatic values, nutrients levels and volatile profiles during dehydration. This study suggests variable temperature drying is a practical approach to reduce drying time, save costs, and maintain the commercial appeal of chili peppers.

Purpose: The objective is to create a comprehensive model that integrates clinical, semantic, and radiomics features to forecast the 5-year progression-free survival (PFS) of individuals diagnosed with non-distant metastatic Nasopharyngeal Carcinoma (NPC). Methods: In a retrospective analysis, we included clinical and MRI data from 313 patients diagnosed with primary NPC. Patient classification into progressive and non-progressive categories relied on the occurrence of recurrence or distant metastasis within a 5-year timeframe. Initial screening comprised clinical features and statistically significant image semantic features. Subsequently, MRI radiomics features were extracted from all patients, and optimal features were selected to formulate the Rad-Score.Combining Rad-Score, image semantic features, and clinical features to establish a combined model Evaluation of predictive efficacy was conducted using ROC curves and nomogram specific to NPC progression. Lastly, employing the optimal ROC cutoff value from the combined model, patients were dichotomized into high-risk and low-risk groups, facilitating a comparison of 10-year overall survival (OS) between the groups. Results: The combined model showcased superior predictive performance for NPC progression, reflected by AUC values of 0.84, an accuracy rate of 81.60%, sensitivity at 0.77, and specificity at 0.81 within the training group. In the test set, the AUC value reached 0.81, with an accuracy of 74.6%, sensitivity at 0.82, and specificity at 0.66. Conclusion: The amalgamation of Rad-Score, clinical, and imaging semantic features from multi-parameter MRI exhibited significant promise in prognosticating 5-year PFS for non-distant metastatic NPC patients. The combined model provided quantifiable data for informed and personalized diagnosis and treatment planning.

Abstract The proper axial length of the eye is crucial for achieving emmetropia. In this study, we present a wireless battery-free eye modulation patch designed to correct high myopia and prevent relapse. The patch consists of piezoelectric transducers, an electrochemical micro-actuator, a drug microneedle array, μ-LEDs, a flexible circuit, and biocompatible encapsulation. The system can be wirelessly powered and controlled using external ultrasound. The electrochemical micro-actuator plays a key role in precisely shortening the axial length by driving the posterior sclera inward. This ensures accurate scene imaging on the retina for myopia eye. The drug microneedle array delivers riboflavin to the posterior sclera, and μ-LEDs’ blue light induces collagen cross-linking, reinforcing sclera strength. In vivo experiments demonstrate that the patch successfully reduces the rabbit eye’s axial length by ~1217 μm and increases sclera strength by 387%. The system operates effectively within the body without the need for batteries. Here, we show that the patch offers a promising avenue for clinically treating high myopia.

Abstract Background The number and proportion of the elderly population have been continuously increasing in China, leading to the elevated prevalence of chronic diseases and multimorbidity, which ultimately brings heavy burden to society and families. Meanwhile, the status of multimorbidity tends to be more complex in elderly inpatients than community population. In view of the above concerns, this study was designed to investigate the health status of elderly inpatients by analyzing clinical data in Chinese People's Liberation Army (PLA) General Hospital from 2008 to 2019, including the constitution of common diseases, comorbidities, the status of multimorbidity, in-hospital death and polypharmacy among elderly inpatients, so as to better understand the diseases spectrum and multimorbidity of elderly inpatients and also to provide supporting evidence for targeted management of chronic diseases in the elderly. Methods A clinical inpatients database was set up by collecting medical records of elderly inpatients from 2008 to 2019 in Chinese PLA General Hospital, focusing on diseases spectrum and characteristics of elderly inpatients. In this study, we collected data of inpatients aged ≥ 65 years old, and further analyzed the constitution of diseases, multimorbidity rates and mortality causes in the past decade. In addition, the prescriptions were also analyzed to investigate the status of polypharmacy in elderly inpatients. Results A total of 210,169 elderly patients were hospitalized from January 1st, 2008 to December 31st, 2019. The corresponding number of hospitalizations was 290,833. The average age of the study population was 72.67 years old. Of the total population, 73,493 elderly patients were re-admitted within one year, with the re-hospitalization rate of 25.27%. Malignant tumor, hypertension, ischemic heart disease, diabetes mellitus and cerebrovascular disease were the top 5 diseases. Among the study population, the number of patients with two or more long-term health conditions was 267,259, accounting for 91.89%, with an average of 4.68 diseases. In addition, the average number of medications taken by the study population was 5.4, among which, the proportion of patients taking more than 5 types of medications accounted for 55.42%. Conclusions By analyzing the constitution of diseases and multimorbidity, we found that multimorbidity has turned out to be a prominent problem in elderly inpatients, greatly affecting the process of healthy aging and increasing the burden on families and society. Therefore, multidisciplinary treatment should be strengthened to make reasonable preventive and therapeutic strategies to improve the life quality of the elderly. Meanwhile, more attention should be paid to reasonable medications for elderly patients with multimorbidity to avoid preventable side effects caused by irrational medication therapy.

Abstract Background Anxiety and depression can influence adherence to Pre-exposure Prophylaxis (PrEP). However, there is limited research on the temporal dynamics of anxiety and depression among men who have sex with men (MSM) using PrEP. Methods From December 2018 to November 2020, we administered the Hospital Anxiety and Depression Scale (HADS) to participants in the China Real-World Oral Intake of PrEP (CROPrEP) to measure their anxiety and depression levels. The group-based trajectory model (GBTM) depicted the dynamic changes of anxiety and depression scores over time. Results A total of 1023 MSM were included, with 4523 follow-up assessments. The GBTM categorized the trajectories into three distinct patterns: consistently low (54.8% for anxiety, 60.7% for depression), consistently moderate (39.3% for anxiety, 31.4% for depression), and high but bell-shaped (5.9% for anxiety, 7.9% for depression). Higher anxiety levels were associated with being aged 18–30 years old, earning less than US$619 per month, female-identifying, adopting the bottom sexual role with men, and having two or more anal sex partners in the past three months; similarly, higher depression levels correlated with a monthly income under US$619, female-identifying, sexual behavior as bottom and a positive syphilis at baseline. PrEP adherence was notably lower in the high but bell-shaped anxiety and depression group compared to the other groups, particularly at the 12th-month follow-up. Conclusions Close monitoring of anxiety and depression levels in MSM on PrEP is crucial. Provision of targeted mental health support is essential to enhance PrEP effectiveness.

Abstract Objective This study aims to investigate the experiences of parents who have experienced bereavement in their efforts to preserve memories of their deceased child. Methods Employing a qualitative meta-synthesis approach, this study systematically sought relevant qualitative literature by conducting searches across various electronic databases, including PubMed, Embase, CINAHL, PsycINFO, Web of Science, Cochrane Library, and Wiley, up until July 2023. Results Nine studies are eligible for inclusion and included in the meta-synthesis. Three overarching categories are identified: (1) Affirming the Significance of Memory Making. (2) Best Practices in Memory Making. (3) Barriers to Effective Memory Making. Conclusion Bereaved parents highly value the act of creating lasting memories, emphasizing its profound significance. While forming these memories, it is imperative to offer family-centered care and honor diverse preferences and needs. It is essential to offer effective support to parents, offering them a range of choices. Furthermore, a more comprehensive examination of memory-making practices is required to better understand their influence on parents’ recollections of their deceased child.

Abstract Breast cancer (BRCA) has a high incidence and mortality rate among women. Different molecular subtypes of breast cancer have different prognoses and require personalized therapies. It is imperative to find novel therapeutic targets for different molecular subtypes of BRCA. Here, we demonstrated for the first time that Cytochromeb561 (CYB561) is highly expressed in BRCA and correlates with poor prognosis, especially in HER2-positive BRCA. Overexpression of CYB561 could upregulate macroH2A (H2AFY) expression in HER2-positive BRCA cells through inhibition of H2AFY ubiquitination, and high expression of CYB561 in HER2-positive BRCA cells could promote the proliferation and migration of cells. Furthermore, we have demonstrated that CYB561 regulates H2AFY expression, thereby influencing the expression of NF-κB, a downstream molecule of H2AFY. These findings have been validated through in vivo experiments. In conclusion, we propose that CYB561 may represent a novel therapeutic target for the treatment of HER2-positive BRCA. Graphical abstract CYB561 promotes the proliferation of HER2+ BRCA cells: CYB561 enhances the expression of H2AFY by inhibiting its ubiquitination, which leads to an increase expression of NF-κB in the nucleus. H2AFY, together with NF-κB, promotes the proliferation of HER2+ BRCA cells.

Analysis of water balance in the middle reaches of the Yellow River is important for the effective water resources management, ecological protection, and high-quality development in the Yellow River Basin. The Qinhe River Basin, located at the end of the middle reaches of the Yellow River, has serious water problems, such as, river interruption and insufficient inflow into the Yellow River, due to the implementation of the upstream water diversion policy and the increase in domestic and industrial water use. To address the water problems, the water resource demand, water supply capacity, and supply-demand balance of the basin were analyzed based on the ecological water demand. The results show that (1) the spatial distribution of water supply and water demand in the Qinhe River basin is heterogeneous. All the upstream river reaches in the Shanxi Province are able to guarantee the ecological water demand in the river channel, while in the downstream Henan Province, only the minimum water demand can be met; (2) the total suppliable water resources in the Qinhe River basin is 10.04×108 m3, and the sum of industrial, domestic, and ecological water use outside the river channel is 8.89×108 m3. The remaining water in the river channel is only 1.15×108 m3, which can only meet the minimum ecological water demand; (3) the amount of surface water used by industrial production and life in the basin will be 6.98×108 m3 in 2030, and the total amount of water use will be 9.81×108 m3, resulting in that the remaining water cannot support the minimum ecological water demand. We pose five suggestions for the water problem in the Qinhe River Basin: Reducing the industrial water consumption, improving the water utilization rate of agricultural irrigation, promoting water conservation technologies with high effectiveness, and improving the ecological environment. This study can provide basic information for the effective water resources management in the Qinhe River basin.

Abstract Background The pathogenesis of cardiac arrhythmias is multifaceted, encompassing genetic, environmental, hemodynamic, and various causative factors. Emerging evidence underscores a plausible connection between gut flora, serum metabolites, and specific types of arrhythmias. Recognizing the role of host genetics in shaping the microbiota, we employed two-sample Mendelian randomization analyses to investigate potential causal associations between gut flora, serum metabolites, and distinct arrhythmias. Methods Mendelian randomization methods were deployed to ascertain causal relationships between 211 gut flora, 575 serum metabolites, and various types of arrhythmias. To ensure the reliability of the findings, five complementary Mendelian randomization methods, including inverse variance weighting methods, were employed. The robustness of the results was scrutinized through a battery of sensitivity analyses, incorporating the Cochran Q test, leave-one-out test, and MR-Egger intercept analysis. Results Eighteen gut flora and twenty-six serum metabolites demonstrated associations with the risk of developing atrial fibrillation. Moreover, ten gut flora and fifty-two serum metabolites were linked to the risk of developing supraventricular tachycardia, while eight gut flora and twenty-five serum metabolites were associated with the risk of developing tachycardia. Additionally, six gut flora and twenty-one serum metabolites exhibited associations with the risk of developing bradycardia. Conclusion This study revealed the potential causal relationship that may exist between gut flora, serum metabolites and different cardiac arrhythmias and highlights the need for further exploration. This study provides new perspectives to enhance diagnostic and therapeutic strategies in the field of cardiac arrhythmias.

Abstract Background Cognitive impairment is associated with dysregulated immune responses. Emerging evidence indicates that Th17 cells and their characteristic cytokine-IL-17 are receiving growing interest in the pathogenesis of cognitive decline. Here, we focus on the involvement of Th17 cells in mild cognitive impairment (MCI) and the possible mechanism of cholesterol metabolite-27-hydroxycholesterol (27-OHC). Methods 100 individuals were recruited into the nested case–control study who completed cognition assessment and the detection of oxysterols and Th17-related cytokines in serum. In addition, mice were treated with 27-OHC and inhibitors of RORγt and Foxp3 (Th17 and Treg transcription factors), and the factors involved in Th17/Treg balance and amyloidosis were detected. Results Our results showed there was enhanced 27-OHC level in serum of MCI individuals. The Th17-related cytokines homeostasis was altered, manifested as increased IL-17A, IL-12p70, IL-23, GM-CSF, MIP-3α and TNF-α but decreased IL-13, IL-28A and TGF-β1. Further, in vivo experiments showed that 27-OHC induced higher immunogenicity, which increased Th17 proportion but decreased Treg cells in peripheral blood mononuclear cells (PBMCs); Th17 proportions in hippocampus, and IL-17A level in serum and brain were also higher than control mice. The fluorescence intensity of amyloid-β (Aβ) and the precursor of amyloid A amyloidosis–serum amyloid A (SAA) was increased in the brain of 27-OHC-treated mice, and worse learning and memory performance was supported by water maze test results. While by inhibiting RORγt in 27-OHC-loaded mice, Th17 proportions in both PBMCs and hippocampus were reduced, and expressions of IL-17A and TGF-β1 were down- and up-regulated, respectively, along with a decreased amyloidosis in brain and improved learning and memory decline. Conclusions Altogether, our results demonstrate that excessive 27-OHC aggravates the amyloidosis and leads to cognitive deficits by regulating RORγt and disturbing Th17/Treg balance.

Abstract Photochemical glycosylation has attracted considerable attention in carbohydrate chemistry. However, to the best of our knowledge, visible-light-promoted glycosylation via photoactive glycosyl donor has not been reported. In the study, we report a photosensitizer-free visible-light-mediated glycosylation approach using a photoactive 2-glycosyloxy tropone as the donor. This glycosylation reaction proceeds at ambient temperature to give a wide range of O-glycosides or oligosaccharides with yields up to 99%. This method is further applied in the stereoselective preparation of various functional glycosyl phosphates/phosphosaccharides, the construction of N-glycosides/nucleosides, and the late-stage glycosylation of natural products or pharmaceuticals on gram scales, and the iterative synthesis of hexasaccharide. The protocol features uncomplicated conditions, operational simplicity, wide substrate scope (58 examples), excellent compatibility with functional groups, scalability of products (7 examples), and high yields. It provides an efficient glycosylation method for accessing O/N-glycosides and glycans.

Abstract Objective This study, based on the China Hainan Centenarians Cohort Study (CHCCS), aims to comprehensively describe the characteristic of daytime, night and total sleep duration, sleep quality and different sleep mode of Hainan centenarians and their associations with activity of daily living (ADL) functions. Method The baseline data of CHCCS was used. ADL function was evaluated the Bathel index, sleep quality was evaluated by Pittsburgh sleep quality index (PSQI), sleep status including daytime, night and total sleep duration as well as sleep quality and sleep mode. Multivariate logistic regression model was used to explore the association between sleep status and ADL disability and ADL moderate & severe disability. Results A total of 994 centenarians were included in this study with the age range 100–116 years old. Compared with the centenarians who sleep 6–9 h at night and 9 h at night and sleep ≥ 2 h in the daytime and ADL disability was 2.93 (95% CI: 1.02–8.44), and adjusted OR of ADL moderate & severe disability was 2.75 (95% CI: 1.56–4.83). Compared with centenarians who sleep for 7–9 h and have good sleep quality, centenarians who sleep for > 9 h and have poor sleep quality have an increased risk of ADL moderate & severe disability (OR = 3.72, 95% CI: 1.54–9.00). Conclusion Relation between sleep duration and ADL disability was more significant compared with sleep quality in Hainan centenarians. Poor sleep quality can aggravate the relationship between sleep duration and ADL moderate & severe disability.

Tongxie Yaofang (TXYF) has therapeutic effect on the ulcerative colitis (UC) with liver depression and spleen deficiency syndrome. This study investigated the changes in the gut microbiota of UC rats treated with TXYF. Wistar rats were divided into three groups: Control, dinitrobenzene sulfonic acid (DNBS)-colitis, and DNBS + TXYF (n = 8 per group). UC model was constructed via intrarectally injection of DNBS (25 mg DNBS and 0.25 mL 50% ethanol); rats in DNBS + TXYF group were administered with TXYF (20.8 g/kg) for 21 days. Physiological parameters were measured. Five samples from each group were selected for metagenomic analysis. TXYF treatment significantly reduced disease activity index, colon mucosal damage index, and tumor necrosis factor-alpha level. TXYF treatment prevented DNBS-induced dysregulation of gut microbial communities. Compared with DNBS-colitis group, the abundance of Firmicutes increased significantly and that of Bacteroidetes and Proteobacteria decreased in DNBS + TXYF group. Pathways such as protein processing in the endoplasmic reticulum pathway was enriched in the DNBS-colitis group, whereas it was decreased in the DNBS + TXYF group. Thus, TXYF treatment could effectively restore the dysregulation of intestinal flora induced by UC.

Summary: Reliable blood-based tests for identifying early-stage breast cancer remain elusive. Employing single-cell transcriptomic sequencing analysis, we illustrate a close correlation between nucleotide metabolism in the breast cancer and activation of regulatory T cells (Tregs) in the tumor microenvironment, which shows distinctions between subtypes of patients with triple-negative breast cancer (TNBC) and non-TNBC, and is likely to impact cancer prognosis through the A2AR-Treg pathway. Combining machine learning with absolute quantitative metabolomics, we have established an effective approach to the early detection of breast cancer, utilizing a four-metabolite panel including inosine and uridine. This metabolomics study, involving 1111 participants, demonstrates high accuracy across the training, test, and independent validation cohorts. Inosine and uridine prove predictive of the response to neoadjuvant chemotherapy (NAC) in patients with TNBC. This study deepens our understanding of nucleotide metabolism in breast cancer development and introduces a promising non-invasive method for early breast cancer detection and predicting NAC response in patients with TNBC.

Diversifying cultivation management, including different crop rotation patterns and soil amendment, are effective strategies for alleviating the obstacles of continuous cropping in peanut (Arachis hypogaea L.). However, the peanut yield enhancement effect and temporal changes in soil chemical properties and microbial activities in response to differential multi-year crop rotation patterns and soil amendment remain unclear. In the present study, a multi-year localization experiment with the consecutive application of five different cultivation managements (including rotation with different crops under the presence or absence of external quicklime as soil amendment) was conducted to investigate the dynamic changes in peanut nutrient uptake and yield status, soil chemical property, microbial community composition and function. Peanut continuous cropping led to a reduction in peanut yield, while green manure-peanut rotation and wheat-maize-peanut rotation increased peanut yield by 40.59 and 81.95%, respectively. A combination of quicklime application increased yield by a further 28.76 and 24.34%. Alterations in cultivation management also strongly affected the soil pH, nutrient content, and composition and function of the microbial community. The fungal community was more sensitive than the bacterial community to cultivation pattern shift. Variation in bacterial community was mainly attributed to soil organic carbon, pH and calcium content, while variation in fungal community was more closely related to soil phosphorus content. Wheat-maize-peanut rotation combined with quicklime application effectively modifies the soil acidification environment, improves the soil fertility, reshapes the composition of beneficial and harmful microbial communities, thereby improving soil health, promoting peanut development, and alleviating peanut continuous cropping obstacles. We concluded that wheat-maize-peanut rotation in combination with quicklime application was the effective practice to improve the soil fertility and change the composition of potentially beneficial and pathogenic microbial communities in the soil, which is strongly beneficial for building a healthy soil micro-ecology, promoting the growth and development of peanut, and reducing the harm caused by continuous cropping obstacles to peanut.

Abstract Objective The aim of this paper is to investigate the effect of long noncoding RNA (lncRNA) MIR100HG on the proliferation and metastasis of lung cancer cells by mediating the microRNA (miR)−5590‐3p/DCBLD2 axis. Methods RNA levels of MIR100HG, miR‐5590‐3p, and DCBLD2 in lung cancer tissues and cells were detected by quantitative reverse‐transcription polymerase chain reaction, and protein level was assessed by Western blot. Effects of MIR100HG or miR‐5590‐3p on proliferation, migration, and invasion of lung cancer cells were detected by Cell Counting Kit‐8, colony formation, and Transwell assays. Luciferase reporter assay and RNA‐immunoprecipitation assay confirmed the target relationship between miR‐5590‐3p and MIR100HG or DCBLD2. Results MIR100HG and DCBLD2 were highly expressed, while miR‐5590‐3p was lowly expressed in lung cancer tissues and cells. Silencing MIR100HG or upregulating miR‐5590‐3p impeded lung cancer cell proliferation, migration, and invasion. MIR100HG could up‐regulate DCBLD2 by sponging miR‐5590‐3p. Downregulation of miR‐5590‐3p partly overturned the suppressive effect of silencing MIR100HG on lung cancer cell proliferation and metastasis, and overexpression of DCBLD2 also reversed the effect of overexpression of miR‐5590‐3p on lung cancer cell proliferation and metastasis. Conclusion LncRNA MIR100HG promotes lung cancer progression by targeting and negatively regulating DCBLD2 through binding with miR‐5590‐3p.

Vapor pressure deficit (VPD) shows significant spatial and temporal variability in the context of global climate change, which is important for studying the implications of climate change on the structure and function of ecosystems to analyze the effects of VPD on vegetation dynamics. Spatial patterns of vegetation sensitivity to VPD have been recently investigated, however, the feedback of different vegetation types to VPD may vary depending on physiological characteristics, it is unclear how different types influence the sensitivity to VPD. In this study, the ERA5-Land reanalysis time-series dataset was used to analyze the spatial and temporal trends of VPD under different vegetation types. It was found that VPD showed an increasing trend in vegetated areas over the past 20 years with large spatial heterogeneity, generally increasing with drying conditions. On this basis, the spatial patterns of vegetation sensitivity to VPD and temporal trends in sensitivity were evaluated over the past 20 years in China using the enhanced vegetation index (EVI) and near-infrared reflectance of vegetation (NIRv) which can describe vegetation dynamics. The results show that the sensitivities under the two indices have high spatial consistency, with northeastern and central China showing positive sensitivities and southern China showing negative sensitivities, respectively. The positive sensitivities are relatively high for Deciduous Broadleaf Forests (DBF), Deciduous Needleleaf Forests (DNF), Grasslands (GL), and Croplands (CL) types, while the negative sensitivities are larger for Shrublands (SL) and Savannas (SA) types. Under different climatic zones, the sensitivity of CL and GL are independent of climatic zones (both showing positive), while the sensitivity of SL is negative in the Humid zone and positive in the Semi-Arid zone. Temporally, the sensitivity showed a slow increasing trend over the last 20 years. In terms of vegetation types, sensitivities of Evergreen Broadleaf Forests (EBF), DBF, GL and CL types showed a significant increasing trend (p

This paper offers an in-depth investigation into various quantitative assessment methods used to quantify the supply regulation capacity in new types of power systems under different conditions. As new forms of energy, including renewables, are increasingly becoming the predominant sources of power systems, the traditional systems are undergoing transformative modifications to efficiently address the issue of power generation and consumption fluctuations. In this regard, this paper proposes an original framework that combines advanced statistical methods and machine learning. The primary purpose of the framework is to identify the level of resilience and flexible adaptability of new power systems. The paper presents the results of the simulations and real-world applications of the proposed measurement methods in enhancing power supply reliability and efficiency in all conditions. The implications based on the results will be beneficial to policymakers and other specialists who are making decisions involving designing and optimizing modern power systems. Furthermore, the paper aims to contribute to the existing discussion by providing further insights into the effectiveness of the proposed methods of measurement.

Abstract Background The N6‐methyladenosine (m6A) dynamics in the progression of intervertebral disc (IVD) aging remain largely unknown. This study aimed to explore the distribution and pattern of m6A modification in nucleus pulpous (NP) tissues of rats at different ages. Methods Histological staining and MRI were performed to evaluate the degeneration of IVD. The expression of m6A modifiers was analyzed using qRT‐PCR and western blot. Subsequently, methylated RNA immunoprecipitation next generation sequencing and RNA‐seq were conducted to identify differences in m6A methylome and transcriptome of NP tissues. Results Compared to 2‐month‐old rats, we found significant changes in the global m6A level and the expression of Mettl3 and FTO in NP tissues from 20‐month‐old rats. During the progression of NP aging, there were 1126 persistently differentially m6A peaks within 931 genes, and 51 persistently differentially expressed genes. GO and KEGG analyses showed that these m6A peaks and m6A modified genes were mainly engaged in the biological processes and pathways of intervertebral disc degermation (IDD), such as extracellular matrix metabolism, angiogenesis, inflammatory response, mTOR and AMPK signaling pathways. Meanwhile, conjoint analyses and Venn diagram revealed a total of 405 aging related genes contained significant methylation and expression levels in 20‐month‐old rats in contrast to 2‐month‐old and 10‐month‐old rats. Moreover, it was found that four aging related genes with hypermethylated modification including BUB1, CA12, Adamts1, and Adamts4 depicted differentially expressed at protein level, of which BUB1 and CA12 were decreased, while Adamts1 and Adamts4 were increased during the progression of NP aging. Conclusion Collectively, this study elucidated the distribution and pattern of m6A modification during the aging of IVD. Furthermore, the m6A modified genes were involved in the IDD related biological processes and pathways. These findings may provide novel insights into the mechanisms and therapies of IDD from the perspective of aging.

Abstract The short‐wave infrared (SWIR) photoluminescence lifetimes of rare‐earth doped nanoparticles (RENPs) have found diverse applications in fundamental and applied research. Despite dazzling progress in the novel design and synthesis of RENPs with attractive optical properties, existing optical systems for SWIR photoluminescence lifetime imaging are still considerably restricted by inefficient photon detection, limited imaging speed, and low sensitivity. To overcome these challenges, SWIR photoluminescence lifetime imaging microscopy using an all‐optical streak camera (PLIMASC) is developed. Synergizing scanning optics and a high‐sensitivity InGaAs CMOS camera, SWIR‐PLIMASC has a 1D imaging speed of up to 138.9 kHz in the spectral range of 900–1700 nm, which quantifies the photoluminescence lifetime of RENPs in a single shot. A 2D photoluminescence lifetime map can be acquired by 1D scanning of the sample. To showcase the power of SWIR‐PLIMASC, a series of core‐shell RENPs with distinct SWIR photoluminescence lifetimes is synthesized. In particular, using Er3+‐doped RENPs, SWIR‐PLIMASC enables multiplexed anti‐counterfeiting. Leveraging Ho3+‐doped RENPs as temperature indicators, this system is applied to SWIR photoluminescence lifetime‐based thermometry. Opening up a new avenue for efficient SWIR photoluminescence lifetime mapping, this work is envisaged to contribute to advanced materials characterization, information science, and biomedicine.

IntroductionThe brown planthopper (BPH) poses a significant threat to rice production in Asia. The use of resistant rice varieties has been effective in managing this pest. However, the adaptability of BPH to resistant rice varieties has led to the emergence of virulent populations, such as biotype Y BPH. YHY15 rice, which carries the BPH resistance gene Bph15, exhibits notable resistance to biotype 1 BPH but is susceptible to biotype Y BPH. Limited information exists regarding how resistant rice plants defend against BPH populations with varying levels of virulence.MethodsIn this study, we integrated miRNA and mRNA expression profiling analyses to study the differential responses of YHY15 rice to both avirulent (biotype 1) and virulent (biotype Y) BPH.ResultsYHY15 rice demonstrated a rapid response to biotype Y BPH infestation, with significant transcriptional changes occurring within 6 hours. The biotype Y-responsive genes were notably enriched in photosynthetic processes. Accordingly, biotype Y BPH infestation induced more intense transcriptional responses, affecting miRNA expression, defenserelated metabolic pathways, phytohormone signaling, and multiple transcription factors. Additionally, callose deposition was enhanced in biotype Y BPH-infested rice seedlings.DiscussionThese findings provide comprehensive insights into the defense mechanisms of resistant rice plants against virulent BPH, and may potentially guide the development of insect-resistant rice varieties.

Summary: Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan–Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423–1.262) in the azvudine group 0.802 (0.435–1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805–3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546–3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the “National Key R&D Program of China” (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

Abstract Background Liver cancer stem cells (LCSCs) play an important role in hepatocellular carcinoma (HCC), but the mechanisms that link LCSCs to HCC metastasis remain largely unknown. This study aims to reveal the contributions of NRCAM to LCSC function and HCC metastasis, and further explore its mechanism in detail. Methods 117 HCC and 29 non-HCC patients with focal liver lesions were collected and analyzed to assess the association between NRCAM and HCC metastasis. Single-cell RNA sequencing (scRNA-seq) was used to explore the biological characteristics of cells with high NRCAM expression in metastatic HCC. The role and mechanism of NRCAM in LCSC dissemination and metastasis was explored in vitro and in vivo using MYC-driven LCSC organoids from murine liver cells. Results Serum NRCAM is associated with HCC metastasis and poor prognosis. A scRNA-seq analysis identified that NRCAM was highly expressed in LCSCs with MYC activation in metastatic HCC. Moreover, NRCAM facilitated LCSC migration and invasion, which was confirmed in MYC-driven LCSC organoids. The in vivo tumor allografts demonstrated that NRCAM mediated intra-hepatic/lung HCC metastasis by enhancing the ability of LCSCs to escape from tumors into the bloodstream. Nrcam expression inhibition in LCSCs blocked HCC metastasis. Mechanistically, NRCAM activated epithelial-mesenchymal transition (EMT) and metastasis-related matrix metalloproteinases (MMPs) through the MACF1 mediated β-catenin signaling pathway in LCSCs. Conclusions LCSCs typified by high NRCAM expression have a strong ability to invade and migrate, which is an important factor leading to HCC metastasis.

Abstract Background Although hypoalbuminemia was associated with high risk of mortality in community-dwelling older adults, as well as in the hospitalized older adults, little is known among centenarians. And there are limited data on whether having cardiometabolic diseases (CMDs) is associated with additive effects. Methods Baseline examinations including a determination of albumin levels were performed in 1002 Chinese centenarians from January 2014 through to December 2016, and the survival status was subsequently ascertained until 31 May 2021. Cox proportional risk model was performed to assess the risk of all-cause mortality associated with albumin levels and hypoalbuminemia combined with CMDs. Results Of 1002 participants included in the analysis, the mean level of albumin was 38.5 g/L (± standard deviation, 4.0 g/L), and 174 (17.4%) had hypoalbuminemia (albumin

Abstract Background This nationwide survey studied the level of palliative care (PC) access for Chinese patients with cancer among cancer care providers either in tertiary general hospitals or cancer hospitals in China. Methods Using a probability-proportionate-to-size method, we identified local tertiary general hospitals with oncology departments to match cancer hospitals at the same geographic area. A PC program leader or a designee at each hospital reported available PC services, including staffing, inpatient and outpatient services, education, and research, with most questions adapted from a previous national survey on PC. The primary outcome was availability of a PC service. Results Most responders reported that some type of PC service (possibly called “comprehensive cancer care,” “pain and symptom management,” or “supportive care”) was available at their institution (84.3% of tertiary general hospitals, 82.8% of cancer hospitals). However, cancer hospitals were significantly more likely than tertiary general hospitals to have a PC department or specialist (34.1% vs. 15.5%, p 92%), symptom management (> 77%), comprehensive care plans (~ 60%), obtaining advanced directives and do-not-resuscitate orders (~ 45%), referrals to hospice (> 32%), and psychiatric assessment (> 25%). Cancer hospitals were also more likely than tertiary general hospitals to report having inpatient beds for PC (46.3% vs. 30.5%; p = 0.010), outpatient PC clinics (28.0% vs. 16.8%; p = 0.029), educational programs (18.2% vs. 9.0%, p = 0.014), and research programs (17.2% vs. 9.3%, p

Rapid melting, solidification, and a highly powerful laser all contribute to complex heat transfer and flow phenomena during the directed energy deposition (DED) process. To investigate the impact of process parameters on the melt pool and solidification quality during the DED process, a three-dimensional finite element model (FEM) was established. The heat transfer, fluid flow, and solidification during the DED process were investigated. The correct input parameters for GH3536 superalloy were discovered by examining the effects of laser power, scanning speed, and feed rate on the shape of molten pool and interlayer fusion. To forecast the quality of the solidified structure at the cut-off point, temperature gradient and solidification rate discovered in transient thermal distribution were employed. The results shows that the melt pool will grow as a result of high laser power and low scanning speed or feed rate. Concentrating on the expansion of the melt pool is not the best solution because well-solidified microstructure frequently develops in the middle of the parameter set. The correlation between feed rate and laser power is insensitive. At a specific feed rate, the minimum threshold for scanning speed was discovered. When the scanning rate falls below the threshold, uneven solidification structures and anomalous melt pool morphology will take place. The undesirable and potentially fluctuating parameters were indicated, and the laser power and scanning speed range suited for the GH3536 superalloy were summarized. For the feed rate, the center of the parameter set is advised.

Background: As a population ages, blood pressure levels gradually increase, leading to a higher incidence of hypertension and increased cardiovascular diseases risk. This study examines factors affecting hypertension grading among centenarians in the Hainan Province. Methods: Data from 2014 to 2016 were accessed from the cross-sectional database “Hypertension Levels and Epidemiological Characteristics of the Elderly and Centenarians in Hainan province of China”. This study included 690 centenarians with hypertension. Hypertension grading was the dependent variable, analyzed against independent variables including demographic information (sex, age, ethnicity, education level, marital status, cohabitation, and regional distribution), lifestyle factors (smoking, alcohol consumption, and physical activity), body mass index (BMI), and comorbid conditions (diabetes and hyperlipidemia). Logistic regression models, adjusted for these factors, were used to assess the determinants of hypertension grading among the participants. Results: Multivariate regression analysis, after adjusting for other variables, revealed significant associations between BMI, low-density lipoprotein (LDL) levels, and hypertension grades. Individuals with BMI below 18.5 kg/m2 had a 0.614-fold lower risk of developing grade III hypertension (odds ratio [OR]: 0.614, 95% confidence interval [CI]: 0.390–0.966, p = 0.0350) and a 0.586-fold lower risk for grade II hypertension (OR: 0.586, 95% CI: 0.402–0.852, p = 0.0052). Furthermore, individuals with elevated LDL levels had a 6.087-fold greater risk of progressing from grade I to grade III hypertension (OR: 6.087, 95% CI: 1.635–22.660, p = 0.0071) and a 4.356-fold greater risk of progressing from grade II to grade III hypertension (OR: 4.356, 95% CI: 1.052–18.033, p = 0.0423). Additionally, individuals of Li ethnicity had 1.823-fold greater risk of progressing from grade I to grade II hypertension compared to those of Han ethnicity (OR: 1.823, 95% CI: 1.033–3.218, p = 0.0383). Conclusions: A BMI below 18.5 kg/m2, elevated LDL, and ethnicity emerged the primary factors associated with hypertension grading in centenarians. To reduce the risk of hypertension, it is crucial for centenarians to maintain a healthy weight, normal LDL levels, and adopt dietary habits including a low-cholesterol and low-fat diet.

This paper presents a detailed study including LA-ICP-MS zircon U-Pb dating, geochemical, zircon Hf isotope, and whole rock Sr-Nd isotope analysis of magmatic rocks from the Yitong County, Jilin Province, NE China. These data are used to better constrain the Middle Silurian–Middle Devonian tectonic evolution in the eastern segment of the northern margin of the North China Craton (NCC). Zircon U-Pb dating results show that the Ximangzhang tonalite formed in the Late Silurian (425 ± 6 Ma); the basalt, andesite, and metamorphic olivine-bearing basalt in the Fangniugou volcanic rocks formed in the Middle Silurian (428 ± 6.6 Ma) and Middle Devonian (388.4 ± 3.9 Ma, and 384.1 ± 4.9 Ma). The Late Silurian tonalites are characterized by high SiO2 and Na2O and low K2O, MgO, FeOT, and TiO2, with an A/CNK ratio of 0.91–1.00, characteristic of calc-alkaline I-type granite. They are enriched in Rb, Ba, Th, U, and K, and depleted in Nb, Sr, P, and Ti, with positive εNd(t) (+0.35) and εHf(t) (+0.44 to +6.31) values, suggesting that they mainly originated from the partial melting of Meso–Neoproterozoic accretionary lower crustal material (basalt). The Middle Silurian basalts are characterized by low SiO2, P2O5, TiO2, and Na2O and high Al2O3, FeOT, and K2O, enriched in Rb, Ba, Th, U, and K and depleted in Nb, Ta, Sr, P, and Ti, indicative of shoshonitic basalt. The Late Silurian tonalites have positive εNd(t) (+4.91 to +6.18) values and primarily originated from depleted mantle magmas metasomatized by subduction fluids, supplemented by a small amount of subducted sediments and crustal materials. The Middle Devonian volcanic rocks exhibit low SiO2, TiO2, and Na2O and high K2O, and MgO, enriched in Rb, K, and LREEs and depleted in Nb, Ta, Sr, and HREEs, characteristic of shoshonitic volcanic rocks. Their εNd(t) (+2.11 to +3.77) and εHf(t) (+5.90 to +11.73) values are positive. These characteristics indicate that the Middle Devonian volcanic rocks primarily originated from depleted mantle magmas metasomatized by subduction fluids, with the addition of crustal materials or subducted sediments during their formation. Based on regional geological data, it is believed that the study area underwent the following evolutionary stages during the Silurian–Devonian period: (1) active continental margin stage of southward subduction of the Paleo–Asian Ocean (PAO) (443–419 Ma); (2) arc-continent collision stage (419–405 Ma); (3) post-collision extension stage (404–375 Ma); (4) active continental margin stage, with the PAO plate subducting southward once again (375–360 Ma).

A finite element model based on elastic–plastic theory was conducted to study the densification process of iron-based powder metallurgy during high velocity compaction (HVC). The densification process of HVC at different heights was simulated using MSC Marc 2020 software with the Shima–Oyane model, and compared with the experimental results. The numerical simulation results were consistent with the experimental results, proving the reliability of the finite element model. Through finite element analysis and theoretical calculation, the high-speed impact molding process of metal powder was analyzed, and the optimal empirical compaction equation for iron-based powder high-speed impact molding was obtained. At the same time, the influence of impact velocity and impact energy on the relative density distribution cloud map and numerical values of the compact was analyzed.

Alkaline stress with high pH levels could significantly influence plant growth and survival. The enzyme 9-cis-epoxycarotenoid dioxygenase (NCED) serves as a critical bottleneck in the biosynthesis of abscisic acid (ABA), making it essential for regulating stress tolerance. Here, we show that OsNCED3-overexpressing rice lines have increased ABA content by up to 50.90% and improved transcription levels of numerous genes involved in stress responses that significantly enhance seedling survival rates. Overexpression of OsNCED3 increased the dry weight contents of the total chlorophyll, proline, soluble sugar, starch, and the activities of antioxidant enzymes of rice seedlings, while reducing the contents of O2·−, H2O2, and malondialdehyde under hydroponic alkaline stress conditions simulated by 10, 15, and 20 mmol L−1 of Na2CO3. Additionally, the OsNCED3-overexpressing rice lines exhibited a notable increase in the expression of OsNCED3; ABA response-related genes OsSalT and OsWsi18; ion homeostasis-related genes OsAKT1, OsHKT1;5, OsSOS1, and OsNHX5; and ROS scavenging-related genes OsCu/Zn-SOD, OsFe-SOD, OsPOX1, OsCATA, OsCATB, and OsAPX1 in rice seedling leaves. The results of these findings suggest that overexpression of OsNCED3 upregulates endogenous ABA levels and the expression of stress response genes, which represents an innovative molecular approach for enhancing the alkaline tolerance of rice seedlings.

Purpose Countries with unique developmental paths and cultural lineages display significant variations in their out-of-school education systems. In this landscape, Belarus, a vestige of the disbanded Soviet Union, illustrates a distinct out-of-school education system, profoundly shaped by both Soviet and European Union countries' influences. A meticulous examination and scholarly investigation into the Belarusian out-of-school educational framework could enable a more profound comprehension of the metamorphosis and transitions in the out-of-school education systems of nations that surfaced following the dissolution of the Soviet Union. This knowledge could subsequently render a more transparent understanding of the patterns guiding the evolution of global out-of-school educational systems. Design/Approach/Methods This article focuses on out-of-school education in Belarus and discusses its development status and the following main characteristics: the dimensions of its historical development stage, legislative guarantee, essence and extension, training goals, and typical cases. Findings Influenced by historical and geopolitical factors, Belarusian out-of-school education is found to embody the characteristics of both the Soviet Union and European countries. National resources are found to play an important role in the development of out-of-school education, effectively reducing the cost of education for families and shaping students’ positive values. Originality/Value This study analyzes both the history and the current situation of out-of-school education in Belarus and summarizes the country's successful experience in the development of out-of-school education. It can provide a positive point of reference for optimizing the public out-of-school education system in China and exert a positive influence on related educational reforms.

In order to further study the cushioning performance of concave hexagonal cores (CHCs) and expand their application range, the in-plane finite element model of CHCs is established in this paper. A dynamic cushioning coefficient method was proposed to characterize the cushioning performance of CHCs. The dynamic cushioning coefficient curve and minimum dynamic cushioning coefficient (MDCC) of CHCs with different impact velocities and structural parameters are obtained. The influence rules of structural parameters and impact velocities on the MDCC are analyzed; the deformation mode and transformation empirical formula are also obtained. The results show that when other parameters are constant, the MDCC of CHCs decreases with the increase of impact velocity, increases with the increase of wall thickness and side length ratio, and decreases with the increase of expansion angle. The theoretical analysis is consistent with the finite element results, which further verifies the reliability of the model. This paper provides a solid theoretical basis for the industrial application of the cushioning performance of CHCs and forms a key technical support.

Osteoarthritis (OA) is a highly prevalent age-related musculoskeletal disorder that typically results in chronic pain and disability. OA is a multifactorial disease, with increased oxidative stress, dysregulated inflammatory response, and impaired matrix metabolism contributing to its onset and progression. The neurohormone melatonin, primarily synthesized by the pineal gland, has emerged as a promising therapeutic agent for OA due to its potential to alleviate inflammation, oxidative stress, and chondrocyte death with minimal adverse effects. The present review provides a comprehensive summary of the current understanding regarding melatonin as a promising pharmaceutical agent for the treatment of OA, along with an exploration of various delivery systems that can be utilized for melatonin administration. These findings may provide novel therapeutic strategies and targets for inhibiting the advancement of OA.

Osteosarcoma (OS) is a malignant tumor originating from mesenchymal tissue. Pulmonary metastasis is usually present upon initial diagnosis, and metastasis is the primary factor affecting the poor prognosis of patients with OS. Current research shows that the ability to regulate the cellular microenvironment is essential for preventing the distant metastasis of OS, and anoxic microenvironments are important features of solid tumors. During hypoxia, hypoxia-inducible factor-1α (HIF-1α) expression levels and stability increase. Increased HIF-1α promotes tumor vascular remodeling, epithelial-mesenchymal transformation (EMT), and OS cells invasiveness; this leads to distant metastasis of OS cells. HIF-1α plays an essential role in the mechanisms of OS metastasis. In order to develop precise prognostic indicators and potential therapeutic targets for OS treatment, this review examines the molecular mechanisms of HIF-1α in the distant metastasis of OS cells; the signal transduction pathways mediated by HIF-1α are also discussed.