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Abstract Background While small extracellular vesicles (sEVs)-derived circular RNAs (circRNAs) have been emerged as significant players in cancer, the function and underlying mechanism of sEVs-derived circRNAs in anti-cancer immunity remain unclear. Methods Gastric cancer (GC)-derived circRNAs were identified using RNA-seq data from GEO datasets and quantitative reverse transcription polymerase chain reaction (qRT-PCR), RNA immunoprecipitation, dual-luciferase assay, and bioinformatics analysis were performed to investigate the regulatory axis. Transwell assay, wound healing assay, cell counting kit-8 (CCK-8) assay, and xenograft models were used to evaluate its role in GC progression in vivo and in vitro. The delivery of specific circRNAs into sEVs were verified through electron microscopy, nanoparticle tracking analysis (NTA) and fuorescence in situ hybridization (FISH). Flow cytometric analysis and immunohistochemical staining were conducted to find out how specific circRNAs mediated CD8+ T cell exhaustion and resistant to anti-programmed cell death 1 (PD-1) therapy. Results We identified that circ_0001947, packaged by GC-derived sEVs, was obviously elevated in GC and was associated with poor clinical outcome. High circ0001947 level augmented the proliferation, migration, and invasion of GC cells. Mechanistically, circ0001947 sponged miR−661 and miR−671−5p to promote the expression of CD39, which further facilitated CD8+ T cell exhaustion and immune resistance. Conversely, blocking circ_0001947 attenuated CD8+ T cell exhaustion and increased the response to anti-PD−1 therapy. Conclusions Our study manifested the therapeutic potential of targeting sEVs-transmitted circ_0001947 to prohibit CD8+ T cell exhaustion and immune resistance in GC.

The precise correction of atmospheric zenith tropospheric delay (ZTD) is significant for the Global Navigation Satellite System (GNSS) performance regarding positioning accuracy and convergence time. In the past decades, many empirical ZTD models based on whether the gridded or scattered ZTD products have been proposed and widely used in the GNSS positioning applications. But there is no comprehensive evaluation of these models for the whole China region, which features complicated topography and climate. In this study, we completely assess the typical empirical models, the IGGtropSH model (gridded, non-meteorology), the SHAtropE model (scattered, non-meteorology), and the GPT3 model (gridded, meteorology) using the Crustal Movement Observation Network of China (CMONOC) network. In general, the results show that the three models share consistent performance with RMSE/bias of 37.45/1.63, 37.13/2.20, and 38.27/1.34 mm for the GPT3, SHAtropE and IGGtropSH model, respectively. However, the models had a distinct performance regarding geographical distribution, elevation, seasonal variations, and daily variation. In the southeastern region of China, RMSE values are around 50 mm, which are much higher than that in the western region, approximately 20 mm. The SHAtropE model exhibits better performance for areas with large variations in elevation. The GPT3 model and the IGGtropSH model are more stable across different months, and the SHAtropE model based on the GNSS data exhibits superior performance across various UTC epochs.

Objective To study the distribution and trend of HIV-1 drug resistance mutation in Dalian blood donors between 2011 and 2020. Methods The protease-reverse transcriptase (PR-RT) region was sequenced in Dalian blood donors tested HIV-1 positive between 2011 and 2020. Drug resistance mutation (DRM) rate and level of resistance to selected drugs were analyzed by the Stanford HIV Drug Resistance Database. Results DRM were detected in 17.2% (30/174) of samples, while transmitted drug resistance (TDR) was 5.7% (10/174). Between 2011 and 2020, DRM and TDR rates increased significantly in 2019 and reached their highest levels in 2020 (44.4% and 22.2%, respectively). DRM carriage was associated with people with college degree or above and with local residents (P

Abstract Geographical indications (GIs) embody distinctive regional elements characterized by widespread spatial distribution, serving as vital agricultural intellectual properties and significant tourism assets. This case study introduces a multiscale and multi-perspective quantification framework for Shandong Province, focusing on spatial agglomeration, association, and heterogeneity. This approach quantitatively explores GIs’ spatial patterns and influencing mechanisms, analyzing both at the monomer and regional scales, considering static and dynamic perspectives. Leveraging methods such as kernel density analysis, Moran’s I index, Geary’s C index, Internet hot word analysis, and Geodetector, the coastal municipalities, prosperous urban areas, and zones with high-quality arable soils were identified as spatial agglomeration areas for GIs. The study revealed a strong correlation between the spatial distribution pattern of socioeconomic factors and GIs’ spatial density from a static perspective. However, diminished spatial autocorrelation was observed for GIs’ public perception from a dynamic standpoint, indicating a reduced influence of Internet connectivity. The spatial heterogeneity in GIs is determined by multiple interconnected factors, displaying an enhancement effect between any two influencing factors. Among the 15 influencing factors analyzed, urbanization rate; gross value of agricultural, forestry, animal husbandry, and fishery production; and per capita gross domestic product significantly contribute to spatial heterogeneity effects at both urbanization rate, gross value of agriculture, forestry, animal husbandry, fishery production, and per capita gross domestic product significantly contributed to spatial heterogeneity effects at regional and monomer scales. The results suggest that GIs are likely to flourish with regional economic growth. The analytical framework and quantification methods support exploring and sustainably utilizing GIs, improving output quality, and modernizing GIs’ production, ultimately contributing to regional agriculture’s high-quality and sustainable development.

Abstract DNA polymerase ζ (Pol ζ) plays an essential role in replicating damaged DNA templates but contributes to mutagenesis due to its low fidelity. Therefore, ensuring tight control of Pol ζ’s activity is critical for continuous and accurate DNA replication, yet the specific mechanisms remain unclear. This study reveals a regulation mechanism of Pol ζ activity in human cells. Under normal conditions, an autoinhibition mechanism keeps the catalytic subunit, REV3L, inactive. Upon encountering replication stress, however, ATR-mediated phosphorylation of REV3L’s S279 cluster activates REV3L and triggers its degradation via a caspase-mediated pathway. This regulation confines the activity of Pol ζ, balancing its essential role against its mutations causing potential during replication stress. Overall, our findings elucidate a control scheme that fine tunes the low-fidelity polymerase activity of Pol ζ under challenging replication scenarios.

Abstract Cellular senescence is widely acknowledged as having strong associations with cancer. However, the intricate relationships between cellular senescence-related (CSR) genes and cancer risk remain poorly explored, with insights on causality remaining elusive. In this study, Mendelian Randomization (MR) analyses were used to draw causal inferences from 866 CSR genes as exposures and summary statistics for 18 common cancers as outcomes. We focused on genetic variants affecting gene expression, DNA methylation, and protein expression quantitative trait loci (cis-eQTL, cis-mQTL, and cis-pQTL, respectively), which were strongly linked to CSR genes alterations. Variants were selected as instrumental variables (IVs) and analyzed for causality with cancer using both summary-data-based MR (SMR) and two-sample MR (TSMR) approaches. Bayesian colocalization was used to unravel potential regulatory mechanisms underpinning risk variants in cancer, and further validate the robustness of MR results. We identified five CSR genes (CNOT6, DNMT3B, MAP2K1, TBPL1, and SREBF1), 18 DNA methylation genes, and LAYN protein expression which were all causally associated with different cancer types. Beyond causality, a comprehensive analysis of gene function, pathways, and druggability values was also conducted. These findings provide a robust foundation for unravelling CSR genes molecular mechanisms and promoting clinical drug development for cancer.

DNA guanine (G)-quadruplexes (G4s) are unique secondary structures formed by two or more stacked G-tetrads in G-rich DNA sequences. These structures have been found to play a crucial role in highly transcribed genes, especially in cancer-related oncogenes, making them attractive targets for cancer therapeutics. Significantly, targeting oncogene promoter G4 structures has emerged as a promising strategy to address the challenge of undruggable and drug-resistant proteins, such as MYC, BCL2, KRAS, and EGFR. Natural products have long been an important source of drug discovery, particularly in the fields of cancer and infectious diseases. Noteworthy progress has recently been made in the discovery of naturally occurring DNA G4-targeting drugs. Numerous DNA G4s, such as MYC-G4, BCL2-G4, KRAS-G4, PDGFR-β-G4, VEGF-G4, and telomeric-G4, have been identified as potential targets of natural products, including berberine, telomestatin, quindoline, sanguinarine, isaindigotone, and many others. Herein, we summarize and evaluate recent advancements in natural and nature-derived DNA G4 binders, focusing on understanding the structural recognition of DNA G4s by small molecules derived from nature. We also discuss the challenges and opportunities associated with developing drugs that target DNA G4s.

Abstract Background Chemokine (C-C motif) receptor 8 (CCR8) is a chemokine receptor selectively expressed on tumor-infiltrating regulatory T cells (Tregs). Strong immunosuppression mediated by CCR8+ Tregs observed in breast and lung malignancies suggest for their functional significance in cancer therapy. To date, detailed characterization of tumor-infiltrating CCR8+ Tregs cells in colorectal cancer (CRC) is limited. Methods To study the presence and functional involvement of CCR8+ Tregs in CRC, we analyzed the proportions of CCR8-expressing T cells in different T cell subsets in tumor and adjacent normal tissues and peripheral blood mononuclear cells (PBMCs) from CRC patients by Flow cytometry. Also, we compared the distribution of CCR8+ T cells in malignant tissues and peripheral lymphoid organs from a subcutaneous CRC murine model. Bioinformatic analysis was performed to address the significance of CCR8 expression levels in CRC prognosis, immune regulatory gene expression profiles and potential molecular mechanisms associated with CCR8+ Tregs in CRC tumors. Further, we administrated an anti-CCR8 monoclonal antibody to CT26 tumor-bearing mice and examined the antitumor activity of CCR8-targeted therapy both in vivo and in an ex vivo confirmative model. Results Here, we showed that Tregs was predominantly presented in the tumors of CRC patients (13.4 ± 5.8, p

Abstract The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches.

The cardiotoxicity caused by Dox chemotherapy represents a significant limitation to its clinical application and is a major cause of late death in patients undergoing chemotherapy. Currently, there are no effective treatments available. Our analysis of 295 clinical samples from 132 chemotherapy patients and 163 individuals undergoing physical examination revealed a strong positive correlation between intestinal barrier injury and the development of cardiotoxicity in chemotherapy patients. We developed a novel orally available and intestinal targeting protein nanodrug by assembling membrane protein Amuc_1100 (obtained from intestinal bacteria Akkermansia muciniphila), fluorinated polyetherimide, and hyaluronic acid. The protein nanodrug demonstrated favorable stability against hydrolysis compared with free Amuc_1100. The in vivo results demonstrated that the protein nanodrug can alleviate Dox-induced cardiac toxicity by improving gut microbiota, increasing the proportion of short-chain fatty acid-producing bacteria from the Lachnospiraceae family, and further enhancing the levels of butyrate and pentanoic acids, ultimately regulating the homeostasis repair of lymphocytes in the spleen and heart. Therefore, we believe that the integrity of the intestinal barrier plays an important role in the development of chemotherapy-induced cardiotoxicity. Protective interventions targeting the intestinal barrier may hold promise as a general clinical treatment regimen for reducing Dox-induced cardiotoxicity.

Abstract Background Depression is a prevalent mental health problem in postmenopausal women. Given its significant impact on the quality of life and overall well-being of postmenopausal women, there is need for a comprehensive review and meta-analysis of the existing research globally. This systematic review and meta-analysis evaluated the global prevalence of depression and potential associated factors in postmenopausal women. Methods The Cochrane Library, PubMed, EMBASE, Web of Science, MEDLINE, and PsycINFO databases were systematically searched from inception to March 22, 2023. The meta-analysis used the random-effects model to calculate the prevalence of depression rates and associated factors. In addition, subgroup analysis and sensitivity analysis were performed. Publication bias was assessed using funnel plots, Egger’s test, and nonparametric trim-and-fill tests. Results The meta-analysis included 50 studies that involved 385,092 postmenopausal women. The prevalence of depression in postmenopausal women was 28.00% (95% CI, 25.80–30.10). Among the factors relevant to depression among postmenopausal women, marital status (OR: 2.03, 95%CI: 1.33–3.11), history of mental illness (OR: 2.31, 95%CI: 1.50–3.57), chronic disease (OR: 3.13, 95%CI: 2.20–4.44), menstrual cycle (OR: 1.42, 95%CI: 1.17–1.72), abortion numbers (OR: 1.59, 95%CI: 1.40–1.80), menopausal symptoms (OR: 2.10, 95%CI: 1.52–2.90), and hormone replacement therapy (OR: 1.76, 95%CI: 1.31–2.35) were risk factors, while physical activity (OR: 0.56, 95%CI: 0.53–0.59), number of breastfed infants (OR: 0.43, 95%CI: 0.19–0.97), menopause age (OR: 0.44, 95%CI: 0.37–0.51) were preventive factors. Conclusions This study demonstrated that the prevalence of postmenopausal depression is high, and some risk factors and protective factors associated with it have been identified. It is necessary to improve screening and management and optimize prevention and intervention strategies to reduce the harmful effects of postmenopausal depression.

Superalloys play a critical role in aerospace applications due to their exceptional mechanical properties at high temperatures. The application of magnetic fields to regulate superalloys presents novel avenues for optimizing microstructures, controlling solidification defects, and enhancing their high-temperature properties. This paper provides a comprehensive review of research findings on the influence of magnetic fields on the microstructure and properties of superalloys. It systematically elucidates the effects of different types and intensities of magnetic fields on alloy solidification. Moreover, this paper extensively explores the effects of various types of magnetic fields on the phase composition, microstructure, and properties of superalloys, including Ni-based and Co-based alloys, as well as high-entropy alloys. The underlying mechanisms behind the impact of magnetic fields on these alloy types are thoroughly analyzed. Finally, the last section offers a brief summary of the current development status and prospects of magnetic field-regulated superalloys.

Abstract Therapeutic resistance represents a bottleneck to treatment in advanced gastric cancer (GC). Ferroptosis is an iron-dependent form of non-apoptotic cell death and is associated with anti-cancer therapeutic efficacy. Further investigations are required to clarify the underlying mechanisms. Ferroptosis-resistant GC cell lines are constructed. Dysregulated mRNAs between ferroptosis-resistant and parental cell lines are identified. The expression of SOX13/SCAF1 is manipulated in GC cell lines where relevant biological and molecular analyses are performed. Molecular docking and computational screening are performed to screen potential inhibitors of SOX13. We show that SOX13 boosts protein remodeling of electron transport chain (ETC) complexes by directly transactivating SCAF1. This leads to increased supercomplexes (SCs) assembly, mitochondrial respiration, mitochondrial energetics and chemo- and immune-resistance. Zanamivir, reverts the ferroptosis-resistant phenotype via directly targeting SOX13 and promoting TRIM25-mediated ubiquitination and degradation of SOX13. Here we show, SOX13/SCAF1 are important in ferroptosis-resistance, and targeting SOX13 with zanamivir has therapeutic potential.

Abstract Esophageal squamous cell carcinoma (ESCC) is one of most prevalent cancers worldwide, especially in China. Lacking in depth mechanism study, effective targets and therapeutics are desperately needed in the clinic. RNA-binding proteins (RBPs) mediate the localization, stability, and translation of the target transcripts and fine-tune the physiological functions of the proteins encoded. Bioinformatics analysis revealed that IGF2BPs were highly expressed in ESCC tissues and at least participated in the regulation of cell proliferation of ESCC cells. Biological researches demonstrated that IGF2BP2 promoted the cell proliferation, migration and invasion of ESCC KYSE30 and KYSE450 cells. IGF2BP2 could bind to EIF4A1 mRNA by recognition of m6A sites and enhanced translation of EIF4A1. IGF2BPs, as m6A reader, IGF2BPs were oncogenic genes in ESCC by regulating the expression of EIF4A1 through m6A sites. IGF2BP2, EIF4A1 and their targets could serve as potential biomarkers and therapeutic targets for ESCC, offering promising novel approaches for the diagnosis and treatment of ESCC.

ABSTRACT This study reports a significant clinical outcome following the use of bronchoscopic interventional therapy combined with pembrolizumab for treating pulmonary large cell neuroendocrine carcinoma (LCNEC), showcasing a novel approach in managing this aggressive cancer.

Background and purpose: The composite score for insulin resistance (IR), known as the Metabolic Score of Insulin Resistance (METS-IR), serves as an assessment tool for IR and has been previously linked to symptomatic intracranial hemorrhage and poor functional outcomes in patients with acute ischemic stroke (AIS). Despite these associations, the impact of METS-IR on early neurological deterioration (END) in patients with minor AIS who underwent intravenous administration of recombinant tissue-type plasminogen activator (IV-rtPA) remains inadequately established. This investigation explored the link between METS-IR and END in patients with minor AIS receiving IV-rtPA treatment. Methods: In this study, a cohort comprising 425 consecutive patients with National Institutes of Health Stroke Scale Score (NIHSS)≤5 who underwent IV-rtPA treatment was included. The METS-IR was computed using the formula ln METS-IR=ln (2 × FBG + TG) × BMI/ln (HDL). END was defined as a NIHSS ≥2 within 24 h post IV-rtPA administration, while poor functional outcome was defined as a modified Rankin Scale (mRS) of 2–6. Multivariate logistical regression was performed to investigate the association between METS-IR and both poor functional outcomes and END. Results: Among the 425 enrolled patients, 64 (15.1 %) patients experienced END, while 80 (18.8 %) had poor functional outcomes three months post-discharge. Upon adjusting for confounding factors, a higher METS-IR emerged as an independent predictor for both END and poor functional outcomes. Similarly, noteworthy findings were observed when METS-IR was defined as a categorical group. The restricted cubic spline (RCS) analysis indicated a linear relationship between METS-IR and END (P = 0.593 for non-linearity, P = 0.034 for overall). The incorporation of METS-IR into the conventional model resulted in a significant enhancement of predictive accuracy for both END and poor functional outcomes. Conclusion: METS-IR emerges as an independent predictor for END and poor functional outcome at three months post-discharge in patients with minor AIS subjected to IV-rtPA. Considering its simplicity and clinical accessibility as an indicator of IR, METS-IR may hold guiding significance in clinical practice.

BackgroundOvarian cancer is a highly aggressive malignancy with limited therapeutic options and a poor prognosis. Deubiquitinating enzymes (DUBs) have emerged as critical regulators of protein ubiquitination and proteasomal degradation, influencing various cellular processes relevant to cancer pathogenesis. In this study, the research progress between ovarian cancer and DUBs was mapped and visualized using bibliometrics, and the expression patterns and biological roles of DUBs in ovarian cancer were summarized.MethodsStudies related to DUBs in ovarian cancer were extracted from the Web of Science Core Collection (WoSCC) database. VOSviewer 1.6.20, CiteSpace 6.3.R1, and R4.3.3 were used for bibliometric analysis and visualization.ResultsFor analysis 243 articles were included in this study. The number of publications on DUBs in ovarian cancer has gradually increased each year. China, the United States, and the United Kingdom are at the center of this field of research. The Johns Hopkins University, Genentech, and Roche Holding are the main research institutions. David Komander, Zhihua Liu, and Richard Roden are the top authors in this field. The top five journals with the largest publication volumes in this field are Biochemical and Biophysical Research Communications, Journal of Biological Chemistry, PLOS One, Nature Communications, and Oncotarget. Keyword burst analysis identified five research areas: “deubiquitinating enzyme,” “expression,” “activation,” “degradation,” and “ubiquitin.” In addition, we summarized the expression profiles and biological roles of DUBs in ovarian cancer, highlighting their roles in tumor initiation, growth, chemoresistance, and metastasis.ConclusionAn overview of the research progress is provided in this study on DUBs in ovarian cancer over the last three decades. It offers insight into the most cited papers and authors, core journals, and identified new trends.

Introduction Esophageal cancer presents significant challenges due to limited treatment options and poor prognosis, particularly in advanced stages. Dysregulated long non-coding RNAs (lncRNAs) are implicated in cancer progression and treatment resistance. This study investigated the roles of dysregulated lncRNA NONHSAT227443.1, identified through lncRNA-seq, and its downstream target gene MRTFB in esophageal squamous cell carcinoma (ESCC). Methods Dysregulated lncRNAs were identified through lncRNA-seq in esophageal cancer tissues with varying chemotherapy response. The regulatory interaction of overexpressed NONHSAT227443.1 was assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. Functional assays, including cell viability, cell proliferation, and flow cytometry analyses, were performed to comprehensively investigate the influence of NONHSAT227443.1 and its downstream molecules on ESCC. Results NONHSAT227443.1 was significantly overexpressed in paclitaxel plus platinum chemotherapy non-responders and esophageal cancer cell lines. Chemotherapy exposure led to diminished NONHSAT227443.1 expression. NONHSAT227443.1 negatively regulated MRTFB expression, and their combined dysregulation correlated with increased cancer activity, proliferation, and suppressed apoptosis. Diminished MRTFB expression was associated with PI3K/AKT pathway activation. Conclusion Our study provides insights into NONHSAT227443.1 and MRTFB roles in esophageal cancer, contributing to aggressive traits and treatment resistance. NONHSAT227443.1 and MRTFB may serve as potential therapeutic targets to enhance the response to paclitaxel plus platinum chemotherapy in non-responsive cases.

Abstract PARP inhibitors (PARPi) hold substantial promise in treating glioblastoma (GBM). However, the adverse effects have restricted their broad application. Through unbiased transcriptomic and proteomic sequencing, it is discovered that the BET inhibitor (BETi) Birabresib profoundly alters the processes of DNA replication and cell cycle progression in GBM cells, beyond the previously reported impact of BET inhibition on homologous recombination repair. Through in vitro experiments using established GBM cell lines and patient‐derived primary GBM cells, as well as in vivo orthotopic transplantation tumor experiments in zebrafish and nude mice, it is demonstrated that the concurrent administration of PARPi and BETi can synergistically inhibit GBM. Intriguingly, it is observed that DNA damage lingers after discontinuation of PARPi monotherapy, implying that sequential administration of PARPi followed by BETi can maintain antitumor efficacy while reducing toxicity. In GBM cells with elevated baseline replication stress, the sequential regimen exhibits comparable efficacy to concurrent treatment, protecting normal glial cells with lower baseline replication stress from DNA toxicity and subsequent death. This study provides compelling preclinical evidence supporting the development of innovative drug administration strategies focusing on PARPi for GBM therapy.

IntroductionHomosexual transmission has contributed greatly to the current HIV-1 epidemic in Hebei province, China. Dolutegravir (DTG) will be conditionally used as a component of free antiretroviral therapy (ART) according to manual for national free anti-AIDS treatment drugs (2023 edition) issued by China in June 2023. However, current genetic characteristics and pretreatment drug resistance (PDR) to proteinase inhibitors (PIs), reverse transcriptase inhibitors (RTs) and integrase strand transfer inhibitors (INSTIs) of HIV-1 in this population have remained unclear.MethodsSerial consecutive cross-sectional analyses for HIV- 1 infection trend, genetic characteristics, PDR and molecular transmission networks were conducted from 2018 to 2022. All of participants were HIV-1- infected MSM newly diagnosed at the HIV surveillance points (HSPs) in Hebei, China. Evidence of PDR was confirmed using the world health organization (WHO) list for surveillance of drug resistance mutations.ResultsIn this study, a total of 14 HIV-1 subtypes were circulating in the HSPs of Hebei province, China. CRF01_ AE (51.9%, 350/675), CRF07_BC (30.4%, 205/675), B (6.2%, 42/675) and URFs (5.8%, 39/675) were the four most predominant subtypes among MSM. And, CRF07_BC (r > 0) and URFs (r > 0) indicated an increasing trend, respectively; however, CRF01_AE (r

BackgroundThere are limited studies exploring the relationship between physical activity (PA), cognitive function, and the brain processing characteristics in healthy older adults.MethodsA total of 41 participants (42.7 ± 20.5 years, 56.1% males) were included in the data analysis. The International Physical Activity Questionnaire Short Form was used to assess PA levels, and the Chinese version of the Montreal Cognitive Assessment-Basic and the Flanker task were employed to evaluate cognitive function. Furthermore, fMRI technology was utilized to examine brain activation patterns.ResultsThe cognitive function of the older adults was found to be significantly lower compared to the young adults. Within the older adults, those with high levels of PA exhibited significantly higher cognitive function than those with low and medium PA levels. The fMRI data showed significant differences in brain activation patterns among young adults across the different PA levels. However, such difference was not observed among older adults.ConclusionA decline in cognitive function was observed among older adults. There was a significant correlation between the levels of PA and cognitive function in healthy older adults. The study demonstrated significant effects of PA levels on brain activation patterns in inhibitory control-related regions among young adults, while not significant among older adults. The findings suggest that neurological mechanisms driving the relationship between PA and cognitive function may differ between older and young adults.

This study aims to investigate the role of RNF149 and tetraspanin CD63 in lipopolysaccharide/Toll-like receptor 4 (LPS/TLR4) signal transduction. TNF-α was assessed using enzyme-linked immunosorbent assay. The distribution of TLR4 was examined through flow cytometry after CD63 knockdown. Real-time polymerase chain reaction was used to analyze the expression of the target genes RNF149 and CD63 under different conditions. Western blotting was employed to detect gene expression, while immunoprecipitation and confocal microscopy were used to evaluate protein interactions. Transcriptome array data from stimulated monocytes (GSE7547) was obtained from GEO and subjected to bioinformatic analysis. It is suggested that CD63 may serve as a substrate of RNF149, with RNF149 capable of directly interacting with CD63. RNF149 degrades CD63 through covalent modification of CD63 at lysine 29 of the ubiquitin monomer, leading to the formation of a multiubiquitin chain. Both RNF149 and CD63 interact with TLR4, with CD63 promoting LPS/TLR4 signaling and RNF149 inhibits it. CD63 does not impact the distribution of TLR4 on the cell surface and does not directly interact with TIRAP, IRAK4, or TRAF6, but does interact with Myd88.RNF149 plays a negative regulatory role in LPS/TLR4 signal transduction by mediating ubiquitination-induced CD63 degradation.

BackgroundThe objective of this study was to conduct a systematic review and meta-analysis of the clinical application effects of transnasal high flow nasal cannula compared to other conventional modalities for oxygen therapy devices in patients undergoing bronchoscopy.MethodsA comprehensive literature search was conducted in multiple English databases, including PubMed, Web of Science, and Cochrane Library, to collect relevant studies on the application of high flow nasal cannula in patients undergoing bronchoscopy, and conducted a meta-analysis utilizing RevMan 5.4 software, following the predetermined inclusion and exclusion criteria.ResultsA total of 12 studies meeting the inclusion criteria were included, involving 1,631 patients (HFNC group: n = 811, other oxygen therapy group: n = 820). The meta-analysis results demonstrated that HFNC significantly reduced the incidence of hypoxemia and improved the minimum oxygen saturation compared to conventional oxygen therapy (RR = 0.27, 95% CI: 0.18–0.41, p

Abstract Background Lyme borreliosis is the most common tick-borne disease in Europe and is often caused by Borrelia afzelii, which is transmitted by Ixodes ricinus ticks. The prevalence and abundance of infected ticks fluctuate in time and space, influencing human infection risk. Rodents are reservoir hosts for B. afzelii and important feeding hosts for larval ticks. In the study reported here, we examined how variation in rodent abundance is associated with B. afzelii infection prevalence in ticks, the density of nymphs (DON) and the density of infected nymphs (DIN) in the following year. We further analysed the relationships between the abundance of infected rodents and nymphal infection prevalence (NIP) and DIN. Methods We conducted a study that combined experimental and observational approaches on 15 islands (10 small islands and 5 large islands) in Finland. On all of the islands, ticks and rodents were monitored and sampled during the summer of 2019, with the monitoring of tick abundance and sampling continuing into the spring of 2020. On five of the 10 small islands, captured rodents were removed from the island (“removal” islands), and on the other five small islands, captured rodents were released back to the trapping site after marking and sampling (“control” islands). On the five large islands, captured rodents were released back to the trapping site after marking and sampling. The presence of B. afzelii from nymph and rodent samples was examined. Results The results of the experimental study showed that neither treatment (removal), rodent abundance index nor abundance index of infected rodents in 2019 was associated with DON, NIP or DIN in 2020. Based on data from the observational study, the NIP in 2020 decreased with increasing rodent abundance index and abundance index of infected rodents in 2019. However, the DIN in 2020 was not associated with the rodent abundance index or the abundance index of infected rodents in 2019. In addition, in the observational study, DON in 2020 increased with increasing rodent abundance index. Conclusions Our results suggest that low rodent abundance during the tick activity period is not sufficient for reducing the disease hazard and, hence, rodent removal may not be a feasible control measure in natural ecosystems. Graphical abstract

Abstract In this study, the ecological impact of human activities and the space occupied by construction and arable land on the Tibetan Plateau were examined, focusing on changes in the net primary productivity (NPP) as a key indicator of ecological health. With the utilization of land use data and multiyear average NPP data from 2002 to 2020, we analyzed the effects of the conversion of zonal vegetation into construction and arable land on carbon sequestration and oxygen release in Chengguan District, Lhasa city. Our findings indicated a marked spatial difference in the NPP among different land types. Regarding the original zonal vegetation, the NPP ranged from 0.2 to 0.3 kg/m2. Construction land showed a decrease in the NPP, with values ranging from 0.16 to 0.26 kg/m2, suggesting a decrease in ecological productivity. Conversely, arable land exhibited an increase in the NPP, with average values exceeding 0.3 kg/m2. This increase suggested enhanced productivity, particularly in regions where the original zonal vegetation provided lower NPP values. However, this enhanced productivity may not necessarily indicate a positive ecological change. In fact, such increases could potentially disrupt the natural balance of ecosystems, leading to unforeseen ecological consequences. The original zonal vegetation, with NPP values ranging from 0.12 to 0.43 kg/m2, exhibited higher ecological stability and adaptability than the other land types. This wider NPP range emphasizes the inherent resilience of native vegetation, which could sustain diverse ecological functions under varying environmental conditions. These findings demonstrate the urgent need for sustainable land use management on the Tibetan Plateau. This study highlights the importance of considering the ecological impact of land use changes in regional development strategies, ensuring the preservation and enhancement in the unique and fragile plateau ecosystem.

Abstract Allogeneic tumors are eradicated by host immunity; however, it is unknown how it is initiated until the report in Nature by Yaron Carmi et al. in 2015. Currently, we know that allogeneic tumors are eradicated by allogeneic IgG via dendritic cells. AlloIgG combined with the dendritic cell stimuli tumor necrosis factor alpha and CD40L induced tumor eradication via the reported and our proposed potential signaling pathways. AlloIgG triggers systematic immune responses targeting multiple antigens, which is proposed to overcome current immunotherapy limitations. The promising perspectives of alloIgG immunotherapy would have advanced from mouse models to clinical trials; however, there are only 6 published articles thus far. Therefore, we hope this perspective view will provide an initiative to promote future discussion.

Natural basalt can be processed into rod-like basalt fibers (BFs) and flake-like basalt scales (BSs) through high-temperature melting, forming and other processes. BFs and BSs have great application prospects in the field of organic coatings. BFs possess a regular rod-like structure and excellent mechanical properties, which are mainly used to enhance the mechanical properties of organic coatings. BSs possess a relatively irregular flake-like structure, which can form “maze” effects and layered structures to enhance corrosion resistance of organic coatings. However, basalt materials have poor compatibility, adhesion, and dispersion in organic resins due to their chemical inertness, resulting in a weak basalt-resin interface. Basalt-resin interface is an important parameter that determines the service performance of basalt composite coatings. Therefore, it is necessary to improve basalt-resin interface through corresponding strategies, such as chemical etching, chemical grafting and plasma treatment. Firstly, the surface modification strategies for improving basalt-matrix interface were summarized in this paper. Secondly, we discussed the effects of BFs and BSs on corrosion resistance of organic coatings and corrosion protection mechanism of composite coatings. Finally, we reviewed the research progress of modified basalt materials reinforced organic coatings.

Abstract Aberrant upregulation of the ubiquitin-specific protease 14 (USP14) has been found in some malignant tumors, including oral squamous cell carcinoma (OSCC). In this study, we further demonstrated that aberrantly overexpressed USP14 was also closely related to adverse clinicopathological features and poor prognosis in patients with OSCC, so we hypothesized that USP14 might act as a tumor-promoting factor during the progression of OSCC. Notably, we originally proved that USP14 is a deubiquitinating enzyme for phosphofructokinase-1 liver type (PFKL), a key rate-limiting enzyme involved in the glycolytic pathway. USP14 interacts with PFKL and enhances its stability through deubiquitination in OSCC cells, which in turn enhances PFKL-mediated glycolytic metabolism and ultimately promote cellular proliferation, migration, and tumorigenesis. In this work, we have also demonstrated for the first time that USP14 is a critical regulator of glycolysis in OSCC and verified a novel mechanism whereby it is involved in tumor metastasis and growth. Collectively, our findings provide novel insights into the tumor-promoting role of USP14 and establish mechanistic foundations for USP14-targeting therapies.

Abstract Sulphur hexafluoride (SF6) decomposed products analysis is highly critical in the early‐stage fault diagnosis of gas‐insulated switchgear (GIS). Spectrum technology outperforms traditional methods on non‐invasiveness, no sample preparation, and no consumption. Here, the authors present an improved fibre‐enhanced Raman spectroscopy (FERS) as a comprehensive analytical tool to detect a suite of SF6 decomposed products (SO2F2, SOF2, SO2, H2S, CF4, OCS, CO2, and CO). The FERS approach is combined with two iris diaphragms for spatial filtering and a rear‐end reflector for additional Raman signal enhancement. Limits of detection down to 1 × 10−6–8 × 10−6 are achieved for different SF6 decompositions, and quantification of an undefined multigas, sampled from an 800 kV GIS in service, is realised utilising SF6 as the internal standard gas and with a maximum error of 5.5 %. The GIS is diagnosed according to the results and confirmed by an on‐site check. The authors foresee that this technique will provide a route for trace gas analysis in the power industry.

Abstract Plant secondary metabolites can protect organisms against oxidative stress caused by adverse environmental conditions. Cinnamomum camphora (L.) J. Presl contains plentiful terpenoids and is subdivided into 5 chemotypes. To develop natural antioxidants using the plant terpenoids, the terpenoid composition and antioxidant abilities of methanol, ethyl acetate, n-hexane and petroleum ether extracts from linalool and eucalyptol chemotypes were investigated, and the solvent effects on in vitro antioxidant activity of 8 main terpenoids were analyzed. Meanwhile, the in vivo effects of two strong antioxidant terpenoids were evaluated. For the two chemotypes, the 4 solvents exhibited the same extracting effects on the terpenoid types, but methanol extracts contained the highest content of terpenoids, which should contribute to their strongest scavenging activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals. In linalool and eucalyptol chemotype extracts, linalool, eucalyptol, ocimene, α-pinene, D-limonene, terpinene, β-pinene and longifolene were the 8 main terpenoids. Among the 4 solvents, the 8 terpenoids showed the strongest free radical-scavenging activity with methanol as the reaction medium, which might result from strong-polarity methanol easily activating C = C unsaturated bonds in these compounds. This might also contribute to the strongest scavenging activity of methanol extracts against free radicals. Among these main components, ocimene and longifolene separately showed the strongest activity in scavenging DPPH and ABTS free radical. In in vivo assay, the two compounds significantly lowered the reactive oxygen species (ROS) levels in Chlamydomonas reinhardtii, a single-celled model organism, under H2O2 stress, and the lowering effects gradually enhanced with increasing the compound concentration, resulting in the corresponding promoting effect on the algal growth. At the same concentration, longifolene showed the strongest effect on protecting the algal cells against oxidative stress. Therefore, methanol was suitable for extracting terpenoids in natural antioxidant development, and ocimene and longifolene were two strong antioxidant terpenoids without cell toxicity, with the latter having stronger in vivo antioxidant activity. Graphical Abstract

Abstract Background To explore the association between liver metabolism-related indicators in maternal serum and neonatal hyperbilirubinemia (NHB), and further investigate the predictive value of these indicators in NHB-related amino acid metabolism disorders. Methods 51 NHB and 182 No-NHB newborns and their mothers who treated in the Fourth Hospital of Shijiazhuang from 2018 to 2022 were participated in the study. The differences in clinical data were compared by the Mann-Whitney U test and Chi-square test. Multivariate logistic regression was used to analyze the relationship between maternal serum indicators and the occurrence of NHB. The correlation analysis and risk factor assessment of maternal serum indicators with NHB-related amino acid metabolic disorders were performed using Spearman correlation analysis and multivariate logistic regression. Results Compared to the non NHB group, the NHB group had higher maternal serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), ALT/AST, and total bile acid (TBA), while lower levels of serum albumin (ALB), total cholesterol (TC) and high-density lipoprotein (HDL). The levels of alanine (ALA), valine (VAL), ornithine (ORN), and proline (PRO) in the newborns were reduced in NHB group, while arginine (ARG) showed a tendency to be elevated. Multiple logistic regression analysis showed that maternal ALT, AST, ALT/AST, and TBA levels were all at higher risk with the development of NHB, whereas ALB, TC, and HDL levels were negatively associated with NHB development. Increasing maternal TBA level was associated with lower ALA (r=-0.167, p = 0.011), VAL (r=-0.214, p = 0.001), ORN (r=-0.196, p = 0.003), and PRO in the newborns (r=-0.131, p = 0.045). Maternal ALT level was negatively associated with ALA (r=-0.135, p = 0.039), VAL (r=-0.177, p = 0.007), ORN (r=-0.257, p

In this paper, we investigate the problems of sliding mode observer design and observer-based integral sliding mode control for a class of singular bio-economic systems with stochastic disturbance. Initially, we establish a bio-economic system with the alien invasive species and stochastic disturbance. Then, a new integral sliding surface is constructed based on the multiplication of sliding variables and negative definite matrix for the error system. The advantage of this method is that it not only stabilizes the sliding variables, but also eliminates the restrictive assumptions often used in sliding mode control of the singular bio-economic systems with stochastic disturbance. Finally, an augmented system is constructed and the linear matrix inequality technique is used to determine the admissibility of the mean square exponent. Furthermore, an observer-based sliding mode controller is designed so that the reachability conditions can be guaranteed. The validity of the results is verified by a numerical simulation.

Designing virtual characters that are capable of reflecting a sense of personality is a key goal in research and applications in virtual reality and computer graphics. More and more research efforts are dedicated to investigating approaches to construct a diverse, equitable, and inclusive metaverse by infusing expressive personalities and styles into virtual avatars. While most previous work focused on exploring variations in virtual characters’ dynamic behaviors, characters’ visual appearance plays a crucial role in affecting their perceived personalities. This paper presents a series of experiments evaluating the effect of virtual characters’ outfits on their perceived personality. Based on the related psychology research conducted in the real world, we determined a set of outfit factors likely to reflect personality in virtual characters: color, design, and type. As a framework for our study, we used the “Big Five” personality model for evaluating personality traits. To test our hypothesis, we conducted three perceptual experiments to evaluate the outfit parameters’ contributions to the characters’ personality. In our first experiment, we studied the color factor by varying color hue, saturation, and value; in the second experiment, we evaluated the impact of different neckline, waistline, and sleeve designs; and in our third experiment, we examined the personality perception of five outfit types: professional, casual, fashionable, outdoor, and indoor. Significant results offer guidance to avatar designers on how to create virtual characters with specific personality profiles. We further conducted a verification test to extend the application of our findings to animated virtual characters in augmented reality (AR) and virtual reality (VR) settings. Results confirmed that our findings can be broadly applied to both static and animated virtual characters in VR and AR environments that are commonly used in games, entertainment, and social networking scenarios.

Chronic tinnitus is highly prevalent but lacks precise diagnostic or effective therapeutic standards. Its onset and treatment mechanisms remain unclear, and there is a shortage of objective assessment methods. We aim to identify abnormal neural activity and reorganization in tinnitus patients and reveal potential neurophysiological markers for objectively evaluating tinnitus. By way of analyzing EEG microstates, comparing metrics under three resting states (OE, CE, and OECEm) between tinnitus sufferers and controls, and correlating them with tinnitus symptoms. This study reflected specific changes in the EEG microstates of tinnitus patients across multiple resting states, as well as inconsistent correlations with tinnitus symptoms. Microstate parameters were significantly different when patients were in OE and CE states. Specifically, the occurrence of Microstate A and the transition probabilities (TP) from other Microstates to A increased significantly, particularly in the CE state (32-37%, ${p}\le 0.05$ ); and both correlated positively with the tinnitus intensity. Nevertheless, under the OECEm state, increases were mainly observed in the duration, coverage, and occurrence of Microstate B (15-47%, ${p} < 0.05$ ), which negatively correlated with intensity ( $\text{R} < $ -0.513, ${p} < 0.05$ ). Additionally, TPx between Microstates C and D were significantly reduced and positively correlated with HDAS levels ( $\text{R}>$ 0.548, ${p} < 0.05$ ). Furthermore, parameters of Microstate D also correlated with THI grades ( $\text{R} < $ -0.576, ${p} < 0.05$ ). The findings of this study could offer compelling evidence for central neural reorganization associated with chronic tinnitus. EEG microstate parameters that correlate with tinnitus symptoms could serve as neurophysiological markers, contributing to future research on the objective assessment of tinnitus.

As a new integrity authentication technology, subject-sensitive hashing has the ability to achieve subject-sensitive authentication for high-resolution remote sensing (HRRS) images and can provide a security guarantee for their subsequent use. However, existing research on subject-sensitive hashing focuses on improving the structure of the deep neural network of the algorithm to improve the algorithm's performance, which makes it necessary to reconstruct the training dataset or modify the network structure in the face of different integrity authentication requirements. In this article, we delve into the impact of dropout on subject-sensitive hashing and propose a stepwise-drop mechanism to address the robustness and tampering-sensitivity requirements of subject-sensitive hashing. On this basis, a network named stepwise-drop and transformer-based U-net (SDTU-net) is proposed for subject-sensitive hashing of HRRS images. SDTU-net can use our proposed stepwise-drop mechanism to determine the drop rate of different network layers, which makes it possible to adjust the algorithm performance without changing network structure and training data. Experiments show that our SDTU-net based subject-sensitive hashing has better overall performance compared with existing algorithms, especially at medium and low thresholds. Our approach solves the problem that the existing algorithms cannot balance robustness and tamper sensitivity at low thresholds.

Acute kidney injury (AKI) is associated with a high mortality rate. Pathologically, renal ischemia/reperfusion injury (RIRI) is one of the primary causes of AKI, and hypoxia-inducible factor (HIF)-1α may play a defensive role in RIRI. This study assessed the role of hypoxia-inducible factor 1α (HIF-1α)-mediated mitophagy in protection against RIRI in vitro and in vivo. The human tubular cell line HK-2 was used to assess hypoxia/reoxygenation (H/R)-induced mitophagy through different in vitro assays, including western blotting, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and reactive oxygen species (ROS) measurement. Additionally, a rat RIRI model was established for evaluation by renal histopathology, renal Doppler ultrasound, and transmission electron microscopy to confirm the in vitro data. The selective HIF-1α inhibitor LW6 reduced H/R-induced mitophagy but increased H/R-induced apoptosis and ROS production. Moreover, H/R treatment enhanced expression of the FUN14 domain-containing 1 (FUNDC1) protein. Additionally, FUNDC1 overexpression reversed the effects of LW6 on the altered expression of light chain 3 (LC3) BII and voltage-dependent anion channels as well as blocked the effects of HIF-1α inhibition in cells. Pretreatment of the rat RIRI model with roxadustat, a novel oral HIF-1α inhibitor, led to decreased renal injury and apoptosis in vivo. In conclusion, the HIF-1α/FUNDC1 signaling pathway mediates H/R-promoted renal tubular cell mitophagy, whereas inhibition of this signaling pathway protects cells from mitophagy, thus aggravating apoptosis, and ROS production. Accordingly, roxadustat may protect against RIRI-related AKI.

PurposeThis study aimed to systematically evaluate the clinical effects of using transnasal high-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) in patients undergoing gastrointestinal endoscopy.MethodsA comprehensive literature search was conducted from 2004 to April 2024 to collect relevant studies on the application of HFNC in patients undergoing gastrointestinal endoscopy. Multiple Chinese and English databases, including China National Knowledge Infrastructure (CNKI), Wanfang Data, Web of Science, PubMed, and Cochrane Library, were searched systematically for randomized controlled trials (RCTs). Two researchers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. RevMan 5.4 software was utilized for conducting the network meta-analysis.ResultsA total of 12 RCTs involving 3,726 patients were included. Meta-analysis results showed that HFNC reduced the incidence of hypoxemia and improved the minimum oxygen saturation (SpO2) compared with COT [odds ratio (OR) = 0.39, 95% confidence interval (CI): 0.29–0.53], [mean difference (MD) = 4.07, 95% CI: 3.14–5.01], and the difference was statistically significant. However, the baseline SpO2 levels and incidence of hypercapnia were not statistically significantly different between the HFNC and COT groups [MD = −0.21, 95% CI: −0.49–0.07]; [OR = 1.43, 95% CI: 0.95–2.15]. In terms of procedure time, the difference between HFNC and COT was not statistically significant, and subgroup analyses were performed for the different types of studies, with standard deviation in the gastroscopy group (MD = 0.09, 95% CI: −0.07–0.24) and the endoscopic retrograde cholangiopancreatography group (MD = 0.36, 95% CI: −0.50–1.23). The results demonstrated a significant reduction in the adoption of airway interventions in the HFNC group compared to the COT group (OR = 0.16, 95% CI: 0.05–0.53), with a statistically significant difference; this result was consistent with those of the included studies.ConclusionThe application of HFNC improves the incidence of hypoxemia, enhances oxygenation, and reduces airway interventions during gastrointestinal endoscopy. However, HFNC does not significantly affect baseline SpO2, hypercapnia, or procedure time. The limitations of this study must be acknowledged, and further high-quality studies should be conducted to validate these findings.

BackgroundThe incidence of early-onset colorectal cancer (EOCRC) is increasing globally. This study aims to describe the temporal trends of incidence and explore related risk exposures in early-life at the country level based on the GBD 2019.MethodsData on the incidence and attributable risk factors of EOCRC were obtained from the GBD 2019. Temporal trends of age-standardized incidence were evaluated by average annual percentage change (AAPC). Early-life exposures were indicated as summary exposure values (SEV) of selected factors, SDI and GDP per capita in previous decades and at ages 0–4, 5–9, 10–14 and 15–19 years. Weighted linear or non-linear regressions were applied to evaluate the ecological aggregate associations of the exposures with incidences of EOCRC.ResultsThe global age-standardized incidence of EOCRC increased from 3.05 (3.03, 3.07) to 3.85 (3.83, 3.86) per 100,000 during 1990 and 2019. The incidence was higher in countries with high socioeconomic levels, and increased drastically in countries in East Asia and Caribbean, particularly Jamaica, Saudi Arabia and Vietnam. The GDP per capita, SDI, and SEVs of iron deficiency, alcohol use, high body-mass index, and child growth failure in earlier years were more closely related with the incidences of EOCRC in 2019. Exposures at ages 0–4, 5–9, 10–14 and 15–19 years were also associated with the incidences, particularly for the exposures at ages 15–19 years.ConclusionThe global incidence of EOCRC increased during past three decades. The large variations at regional and national level may be related with the distribution of risk exposures in early life.

The identification of diagnostic and therapeutic biomarkers for Alzheimer’s Disease (AD) remains a crucial area of research. In this study, utilizing the Weighted Gene Co-expression Network Analysis (WGCNA) algorithm, we identified RHBDF2 and TNFRSF10B as feature genes associated with AD pathogenesis. Analyzing data from the GSE33000 dataset, we revealed significant upregulation of RHBDF2 and TNFRSF10B in AD patients, with correlations to age and gender. Interestingly, their expression profile in AD differs notably from that of other neurodegenerative conditions. Functional analysis unveiled their involvement in immune response and various signaling pathways implicated in AD pathogenesis. Furthermore, our study demonstrated the potential of RHBDF2 and TNFRSF10B as diagnostic biomarkers, exhibiting high discrimination power in distinguishing AD from control samples. External validation across multiple datasets confirmed the robustness of the diagnostic model. Moreover, utilizing molecular docking analysis, we identified dinaciclib and tanespimycin as promising small molecule drugs targeting RHBDF2 and TNFRSF10B for potential AD treatment. Our findings highlight the diagnostic and therapeutic potential of RHBDF2 and TNFRSF10B in AD management, shedding light on novel strategies for precision medicine in AD.

Background: DIREN is a SHE ethnic medicine with stasis-resolving, hemostasis, clearing heat, and removing toxin effects. It is clinically used in the treatment of gastrointestinal bleeding, such as ulcerative colitis (UC). Aim of the study: Fibrosis is one of the pathological changes in the progression of UC, which can make it challenging to respond to a treatment. We aimed to illuminate the role of DIREN in DSS-induced UC and tried to unveil its related mechanisms from two perspectives: intestinal inflammation and collagen deposition. Materials and methods: A 2.5 % dextran sulfate sodium (DSS) water solution was used to induce colitis in mice. The therapeutic effect of DIREN was assessed using the disease activity index, histopathological score, and colon length. Masson and Sirius Red staining was used to observe the fibrosis in the colon. Apoptosis of colonic epithelial cells was observed by TUNEL immunofluorescence staining. RNA-seq observed differential genes and enrichment pathways. Immunohistochemistry and RT-qPCR were used to detect the expression of molecules related to fibrosis and focal adhesion signaling in colon tissue. Results: The administration of DIREN resulted in a reduction of disease activity index (DAI) in mice with UC while simultaneously promoting an increase in colon length. DIREN mitigated the loss of goblet cells in the colon of UC mice and maintained the integrity of the intestinal mucosa barrier. Masson staining revealed a reduction in colonic fibrosis with DIREN treatment, while Sirius red staining demonstrated a decrease in collagen Ⅰ deposition. DIREN reduced apoptosis of colonic epithelial cells and the expression of genes, such as CDH2, ITGA1, and TGF-β2. Additionally, the results of GSEA analysis of colon tissue transcriptome showed that the differentially expressed genes were enriched in the focal adhesion pathway. DIREN was found to downregulate the protein expression of BAX, N-cadherin, β-catenin, Integrin A1, and Vinculin while upregulating the protein expression of BCL2. Additionally, it led to the co-expression of N-cadherin and α-SMA. Conclusion: DIREN exerts a protective effect against DSS-induced UC by ameliorating colonic fibrosis via regulation of focal adhesion and the WNT/β-catenin signaling pathway, thereby inhibiting fibroblast migration and reducing collagen secretion.

In the context of the growing research interest in multi-component alloys (MAs) and their exceptional performance under extreme environments, the high-temperature oxidation resistance and applications of MAs have attracted significant attention in the field of metallic materials. While the cost-effective and mechanical properties of Co-free MAs are of great importance, their oxidation resistance remains insufficiently understood. In this work, we designed multiple heterogeneous structures within a cast dual-phase Cr30Fe30Ni30Al5Ti5 MA by tailoring the Al and Ti ratio, which consists of body-centered-cubic (BCC) grains reinforced by multi-scale nanoprecipitates (i.e., L21, B2, and η phase) and an L12-strengthened face-centered cubic (FCC) skeleton. Isothermal oxidation experiments at 800 °C, 1000 °C, and 1200 °C with varying exposure durations were conducted. The oxidation kinetics at 800 °C and 1000 °C followed a parabolic law, while both low weight increment and oxidation rate confirm remarkable oxidation resistance. At 800 °C, the oxides mainly consist of Cr2O3 and Al2O3, while are dominated by (TiO2 + Cr2O3) and the mixed oxides of Al2O3, TiO2, and Ti2O above 1000 °C. Importantly, the inability to form a continuous Al2O3 oxide scale at higher temperatures led to a deterioration in oxidation resistance. These findings offer valuable insights into underlying mechanisms contributing to oxidation resistance for Co-free MAs.

The burgeoning issue of landfill leachate, exacerbated by urbanization, necessitates evaluating its biological impact, traditionally overshadowed by physical and chemical assessments. This study harnesses Caenorhabditis elegans, a model organism, to elucidate the physiological toxicity of landfill leachate subjected to different treatment processes: nanofiltration reverse osmosis tail water (NFRO), membrane bioreactor (MBR), and raw leachate (RAW). Our investigation focuses on the modulation of sugar metabolism, particularly trehalose—a disaccharide serving dual functions as an energy source and an anti-adversity molecule in invertebrates. Upon exposure, C. elegans showcased a 60–70% reduction in glucose and glycogen levels alongside a significant trehalose increase, highlighting an adaptive response to environmental stress by augmenting trehalose synthesis. Notably, trehalose-related genes in the NFRO group were up-regulated, contrasting with the MBR and RAW groups, where trehalose synthesis genes outpaced decomposition genes by 20–30 times. These findings suggest that C. elegans predominantly counters landfill leachate-induced stress through trehalose accumulation. This research not only provides insights into the differential impact of leachate treatment methods on C. elegans but also proposes a molecular framework for assessing the environmental repercussions of landfill leachate, contributing to the development of novel strategies for pollution mitigation and environmental preservation.

Abstract Background Numerous studies have demonstrated that brain metastases patients may benefit from intracranial radiotherapy combined with immune checkpoint inhibitors (ICIs). However, it is unclear whether this treatment is effective for patients with small cell lung cancer brain metastases (SCLC‐BMs). Methods We conducted a retrospective study by analyzing medical records of patients with SCLC‐BMs from January 1, 2017 to June 1, 2022. Data related to median overall survival (mOS), median progression‐free survival (mPFS), and intracranial progression‐free survival (iPFS) were analyzed. Results A total of 109 patients were enrolled, of which 60 received WBRT and 49 received WBRT‐ICI. Compared to the WBRT alone cohort, the WBRT‐ICI cohort showed longer mOS (20.4 months vs. 29.3 months, p = 0.021), mPFS (7.9 months vs. 15.1 months, p

Background: Evidence-based psychological interventions exist for individuals with obsessive-compulsive disorder (OCD), but many individuals with OCD are unable to access them because of barriers, such as geographical isolation, treatment cost, and stigma etc. Unguided self-help psychological intervention has emerged as a potential solution to this problem. However, there is limited research on its overall effectiveness. This study aimed to address this gap. Methods: Comprehensive searches from inception to 1st Jan 2023 were conducted in both international (PubMed, Embase, PsycINFO, International clinical trials registry platform of WHO) and Chinese (China National Knowledge Infrastructure, WeiPu, WanFang, Chinese Clinical Trial Registry) databases. The registered protocol is accessible at https://doi.org/10.17605/OSF.IO/FKB5W. We included randomized controlled trials (RCTs) comparing unguided self-help psychological interventions to control groups for individuals with OCD. The primary outcome was OCD symptom severity, with Hedges' g calculated post-intervention. Heterogeneity was deemed to be low, moderate, and high if the I2 value was quantified 25%, 50%, and 75% respectively. Relative Risks (RRs) was calculated for dropout rates post-intervention. Random-effects models were used for all analyses. Results: 12 RCTs comparing unguided self-help psychological interventions to control groups were identified, with a total of 20 comparisons and 769 OCD patients. Overall, unguided self-help psychological interventions demonstrated a significant moderate effect on reducing OCD symptom severity (g = −0.42; 95% CI [−0.69; −0.14]) compared to control groups, with a moderate heterogeneity (I2 = 59%; 95% CI [22.73; 78.38]). This finding remained significant in sensitivity analyses for the self-rated Yale-Brown Obsessive-Compulsive Scale (Y-BOCS; k = 7, g = −0.46; 95% CI [−0.71; −0.2]) and after removing an outlier (g = −0.37; 95% CI [−0.55; −0.19]), but not for the clinician-rated Y-BOCS (k = 4, g = −0.78; 95% CI [−2.75; 1.19]) and Obsessive Compulsive Inventory-Revised (k = 6, g = −0.26; 95% CI [−0.53; 0]). Subgroup analyses revealed a significant difference in effect size between studies conducting intention-to-treat and completers-only analyses (p = .01). The completers-only analyses demonstrated a moderate significant effect (g = −0.65; 95% CI [−1.08; −0.21]), whereas the effect of the intention-to-treat analyses was not significant (g = −0.18; 95% CI [−0.36; 0]). Participants in the unguided self-help groups exhibited a significantly higher dropout rate (RR = 2.08; 95% CI [1.53; 2.81]) compared to control groups. Furthermore, participants recruited from the community had a higher likelihood of dropping out compared to those recruited from clinical settings (p

Abstract This paper investigates a delayed predator-prey model with discontinuous harvesting and Beddington–DeAngelis functional response. Using the theory of differential inclusion theory, the existence of positive solutions in the sense of Filippov is discussed. Under reasonable assumptions and periodic disturbances, the existence of positive periodic solutions of the model is studied based on the theory of Mawhin’s coincidence degree. Finally, through numerical simulation, the correctness and feasibility of the conclusions are verified.

Abstract Postnatal leukocytosis reflects the general condition of inflammatory. Infection and inflammatory reaction have been proven to affect the occurrence of ROP and other visual dysfunction. Infants with a gestational age of

Abstract Background Gaming disorder is a new disease, which is included in the disease unit of disorder caused by addiction in the 11th revision of the International Classification of Diseases. This study examined the symptom characteristics of gaming disorders in Chinese adolescents using the latent profile analysis. Methods Totally, 5988 students (including 3285 boys and 2703 girls; aged 12–18 years) from junior high schools and senior high schools were enrolled. The Gaming Disorder Symptom Questionnaire-21 (GDSQ-21) was used to screen gaming disorder. A latent profile analysis was used for classifying the subgroups based on the extent of gaming usage. The relationship between adolescent gamers and demographic variables was analyzed by logistic regression. Results The results of latent profile analysis supported the models of four latent profiles, which were defined as healthy gamers (Profile 1, 56.83%), impaired control gamers (Profile 2, 26.09%), impaired control-game priority gamers (Profile 3, 9.72%) and gamers with disorder (Profile 4, 7.36%), respectively. Logistic regression analysis found that, compared with girls, boys were more likely to be classified into the group dominated by the impaired gamers, the impaired control-game priority gamers, and the gamers with disorder. Conclusions This study highlighted that the latent profile analysis identified four different groups of adolescent gamers, showing a clearer conceptualization of heterogeneous gamers. Gender and average weekly gaming time can predict the latent profile of adolescents. Our findings may facilitate the design of individualized assessment and early intervention programs for adolescent gamer users based on different gaming usage symptoms.

Objective To analyze the application effect of intelligent information system of transfusion reactions(referred to as the system) in the supervision and management of transfusion reactions. Methods A retrospective analysis was conducted on the clinical data of a total of 67 914 blood transfusion patients in our hospital from January 2018 to August 2023. The patients were divided into the control group (n =36 367, with conventional transfusion management) and the observation group (n =31 547, with management by the system).The incidence of adverse reactions, the supervision and management scores, reporting time and processing time of adverse reactions, and patient satisfaction with blood transfusion in the two groups was observed. Results The incidence of transfusion reactions in the observation group and the control group was 0.23% (72/31 547) and 0.24% (86/36 367), with no statistically significant difference (P>0.05). The quality scores of the reporting, registration, processing and supervision, and the total scores of the observation group were higher than those of the control group:(21.46±2.76) vs (17.38±2.74) points, (21.65±2.80) vs (16.98±3.20) points, (22.30±2.42) vs (18.80±3.15) points, (22.85±2.10) vs (18.55 ± 3.06) points, and (90.38±5.96) vs (75.26 ± 6.10) points, with statistically significant difference(P

We discuss the problem of event-triggered sliding mode control for a class of uncertain switched systems. First, through the pre-designed sliding mode surface, the corresponding sliding mode dynamics of the switched system are obtained. Second, based on the Lyapunov function technique and average dwell time strategy, the exponential stability of the correlated sliding mode dynamics is analyzed. Then, a sliding mode control law is designed by using the event-triggered mechanism, which can drive the state trajectories of the uncertain switched system to the bounded sliding mode region and maintain it there for subsequent time. Finally, a simulation example is given to verify the effectiveness of the proposed method.

Abstract Background Polyunsaturated fatty acids (PUFAs) have demonstrated significant therapeutic potential across a wide range of disease. The aim of this study was to investigate the potential impact of PUFA intake on the prevalence of erectile dysfunction (ED). Methods The study included a total of 3730 participants from the National Health and Nutrition Examination Survey (NHANES) 2001–2004. Univariate analysis, multivariate regression analysis, subgroup analysis and machine learning were utilized to explore the relationship of variables to ED. Dose response curves were constructed to observe the linear or nonlinear relationship between PUFA intake and the prevalence of ED. Propensity score matching (PSM) was used for sensitivity analysis. Finally, the potential mechanistic link between PUFA intake and ED was explored. Results Through univariate and multivariate regression analysis results before and after PSM and XGBoost algorithm model results, arachidonic acid (AA) was chosen as the main research object. The consumption of AA was found to be associated with a decreased prevalence of ED under the fully adjusted model [OR = 0.33 (0.20, 0.56), P