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Abstract To address the fatigue damage issues in continuous beam bridges under vehicle loads, a method using vibration-mixed steel fiber-reinforced concrete to improve critical vulnerable areas of the bridge is proposed, thereby enhancing the bridge’s fatigue resistance. Fatigue performance and micro electron microscopy tests were designed for vibration-mixed steel fiber-reinforced concrete, analyzing its damage conditions and microstructural changes under 0 to 2 million cyclic loads, and the key mechanical parameters of the concrete were determined. Based on this, a numerical analysis model was established to simulate the fatigue damage of continuous beam bridges under moving vehicle loads. The results show that piers made with vibration-mixed steel fiber-reinforced concrete exhibit a 56.86% reduction in compressive damage compared to conventional piers, a reduction in stiffness damage range, and a 29.35% increase in fatigue life.

Abstract With the rapid advancement of implantable electronic medical devices, implantable supercapacitors have emerged as popular energy storage devices. However, supercapacitors inevitably come into direct contact with blood when implanted, potentially causing adverse clinical reactions such as coagulation and thrombosis, impairing the performance of implanted energy storage devices, and posing a serious threat to human health. Therefore, this work aims to design an anticoagulant supercapacitor by heparin doped poly(3, 4-ethylenedioxythiophene) (PEDOT) for possible applications in implantable bioelectronics. Heparin (Hep), the as-known anticoagulant macromolecule acts as the counterion for PEDOT doping to enhance its conductivity, and the bioelectrode material PEDOT: Hep with anticoagulant activity is synthesized via chemical oxidation polymerization. Concurrently, the anticoagulant supercapacitor is constructed through in-situ polymerization, where PEDOT: Hep and bacterial cellulose as electrode material and electrolyte layer, respectively. Owing to the incorporation of heparin, the supercapacitor exhibits high hemocompatibility with hemolysis rate

Objective Few studies have explored the relationship between the pathological characteristics of hallux valgus and surgical outcomes. The aim of our study was to report the influence of pathological characteristics such as the tibial sesamoid position (TSP) and first metatarsal pronation on postoperative functional scores and patient satisfaction with hallux valgus surgery. Methods From June 2017 to December 2022, a retrospective analysis was conducted on patients who underwent hallux valgus surgery at our hospital. Anteroposterior (AP) x‐ray parameters (hallux valgus angle [HVA], intermetatarsal angle [IMA], distal metatarsal articular angle [DMAA], TSP, first metatarsal pronation, and first metatarsophalangeal joint dislocation) (preoperative weight‐bearing, immediate postoperative non‐weight‐bearing, and early postoperative weight‐bearing), visual analog scale (VAS) scores, American Orthopaedic Foot and Ankle Society (AOFAS) forefoot scores, SAFE‐Q self‐administered foot evaluation questionnaire (excluding the Sports Activity subscale), complications, and patient satisfaction were used to describe the outcomes. Correlation analysis and multiple linear regression models were used to identify factors influencing postoperative functional scores and patient satisfaction after hallux valgus surgery. Results Eighty‐one patients (92 feet) whose early radiographic parameters and latest follow‐up scores improved significantly (p 0.05). The R 2 values of the multiple linear regression models predicting postoperative functional scores and patient satisfaction ranged from 0.042 to 0.351. Conclusion TSP and first metatarsal pronation were unrelated to postoperative functional scores or patient satisfaction. This finding enhances surgeons' understanding of the functional prognosis of hallux valgus surgery, particularly aiding in explaining the condition and assessing surgical outcomes.

[Introduction] Transmission towers are crucial infrastructure in power systems, and their wind-induced collapse can cause significant losses to power systems. To find solutions to prevent wind-induced collapse of transmission towers, it is necessary to investigate the causes, contributing factors, and processes of wind-induced collapse. [Method] Research results on wind-induced collapse of transmission towers were reviewed from the perspectives of accident analysis, full-scale tests, wind tunnel tests, and numerical simulations. The relevant research results were analyzed and summarized, and recommendations for subsequent research were provided. [Result] The investigation revealed that the factors contributing to the wind-induced collapse of transmission towers include the presence of weak members in the tower body, defects in the calculation of wind loads on transmission lines in the code, and extreme wind loads not considered in the code. [Conclusion] It is recommended to research extreme wind load models, the impact of crosswind and torsional wind loads, accurate models of single tower and tower line systems, and improvement of relevant regulations in the code.

Abstract Background Chronic insomnia increases the risk of various health problems and mental illness. Existing research suggests promise for both transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in treating chronic insomnia individually. However, the combined effects of tDCS and rTMS on this condition remain unclear. This study aimed to verify the efficacy and safety of tDCS combined with rTMS for the treatment of adult patients with chronic insomnia. Methods This was a randomised double-blind parallel-group controlled study. Overall, 157 participants with chronic insomnia were randomly assigned to one of three neurotherapy regimens: tDCS + rTMS, sham tDCS + rTMS, or tDCS + sham rTMS. All groups received 20 treatment sessions over 4 consecutive weeks. The primary outcome was the change in patients’ sleep as assessed by the Pittsburgh Sleep Quality Index (PSQI) at 2 weeks, 4 weeks, and 3 months of follow-up. The secondary outcome was the assessment of different dimensions of depression and anxiety in patients through the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA), as well as the occurrence of adverse events. Results Throughout the intervention and after the 3-month follow-up, the tDCS + rTMS group had significantly reduced total PSQI scores compared with the other two groups [tDCS + rTMS, 9.21 vs. sham tDCS + rTMS, 10.03; difference − 1.10; 95% confidence interval (CI), − 1.82 to − 0.38; p = 0.003; tDCS + rTMS, 9.21 vs. tDCS + sham rTMS, 10.76; difference − 2.14; 95% CI, − 2.90 to − 1.38; p

Abstract Background Hashimoto's thyroiditis (HT) is an autoimmune disorder with unclear molecular mechanisms. While current diagnosis is well-established, understanding of the gut-thyroid axis in HT remains limited. This study aimed to uncover novel molecular signatures in HT by integrating gut metagenome and host transcriptome data (miRNA/mRNA), potentially elucidating disease pathogenesis and identifying new therapeutic targets. Methods We recruited 31 early HT patients and 30 healthy controls in a two-stage study (discovery and validation). Blood and fecal samples underwent RNA and metagenomic sequencing, respectively. Integrative analysis included differential expression, weighted correlation network, correlation and random forest analyses. Regression models and ROC curve analysis were used to evaluate the significance of identified molecular signatures in HT. Results Integrative analysis revealed subtle changes in gut microbiota diversity and composition in early HT, increased abundance of Bacillota_A and Spirochaetota at the phylum level, and significant differences in 24 genera and 67 species. Ecological network analysis indicated an imbalance in the gut microbiota with reduced inhibitory interactions against pathogenic genera in HT. Functional analysis showed changes in infection- and immune-related pathways. Three characteristic species (Salaquimonas_sp002400845, Clostridium_AI_sp002297865, and Enterocloster_citroniae) were identified as most relevant to HT. Analysis of miRNA and mRNA expression profiles uncovered pathways related to immune response, inflammation, infection, metabolism, proliferation, and thyroid cancer in HT. Based on correlations with HT and interactions between them, six characteristic RNAs (hsa-miR-548aq-3p, hsa-miR-374a-5p, GADD45A, IRS2, SMAD6, WWTR1) were identified. Furthermore, our study uncovered significant gut microbiota-host transcriptome interactions in HT, revealing enrichment in metabolic, immune, and cancer-related pathways, particularly with strong associations among those 9 key molecular signatures. The validation stage confirmed improved HT classification accuracy by combining these signatures (AUC = 0.95, ACC = 0.85), suggesting their potential significance in understanding HT pathogenesis. Conclusion Our study reveals novel molecular signatures linking gut microbiome and host transcriptome in HT, providing new insights into the disease pathogenesis. These findings not only enhance our understanding of the gut-thyroid axis but also suggest potential new directions for therapeutic interventions in HT.

Top-down environmental policies aim to mitigate environmental risks but inevitably lead to economic losses due to the market entry or exit of enterprises. This study developed a universal dynamic agent-based supply chain model to achieve tradeoffs between environmental risk reduction and economic sustainability. The model was used to conduct high-resolution daily simulations of the dynamic shifts in enterprise operations and their cascading effects on supply chain networks. It includes production, consumption, and transportation agents, attributing economic features to supply chain components and capturing their interactions. It also accounts for adaptive responses to daily external shocks and replicates realistic firm behaviors. By coupling high spatial–temporal resolution firm-level data from 18 916 chemical enterprises, this study investigates the economic and environmental impacts of an environmental policy resulting in the closure of 1800 chemical enterprises over three years. The results revealed a significant economic loss of 25.8 billion USD, ranging from 23.8 billion to 31.8 billion USD. Notably, over 80% of this loss was attributed to supply chain propagation. Counterfactual analyses indicated that implementing a staggered shutdown strategy prevented 18.8% of supply chain losses, highlighting the importance of a gradual policy implementation to prevent abrupt supply chain disruptions. Furthermore, the study highlights the effectiveness of a multi-objective policy design in reducing economic losses (about 29%) and environmental risks (about 40%), substantially enhancing the efficiency of the environmental policy. The high-resolution simulations provide valuable insights for policy designers to formulate strategies with staggered implementation and multiple objectives to mitigate supply chain losses and environmental risks and ensure a sustainable future.

Abstract Little is known about how the epigenomic states change during development and evolution in a 3D genome context. Here we use Drosophila pseudoobscura with complex turnover of sex chromosomes as a model to address this, by collecting massive epigenomic and Hi-C data from five developmental stages and three adult tissues. We reveal that over 60% of the genes and transposable elements (TE) exhibit at least one developmental transition of chromatin state. Transitions on specific but not housekeeping enhancers are associated with specific chromatin loops and topologically associated domain borders (TABs). While evolutionarily young TEs are generally silenced, old TEs more often have been domesticated as interacting TABs or specific enhancers. But on the recently evolved X chromosome, young TEs are instead often active and recruited as TABs, due to acquisition of dosage compensation. Overall we characterize how Drosophila epigenomic landscapes change during development and in response to chromosome evolution, and highlight the important roles of TEs in genome organization and regulation.

Abstract Objective Accumulation of extracellular matrix (ECM) proteins in the glomerular mesangial region is a typical hallmark of diabetic nephropathy (DN). However, the molecular mechanism underlying ECM accumulation in the mesangium of DN patients remains unclear. The present study aims to establish a connection between extracellular proteins and DN with the goal of identifying potential biomarkers for this condition. Methods Differentially expressed genes (DEGs) between DN kidney tissue and healthy kidney tissue were analyzed using the public data GSE166239. Two gene lists encoding extracellular proteins were then utilized to identify extracellular protein-differentially expressed genes (EP-DEGs). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were performed on these EP-DEGs. A protein–protein interaction (PPI) network was established to identify key EP-DEGs. Furthermore, the diagnostic ability, immune cell infiltration, and clinical relevance of these EP-DEGs were investigated. Immunohistochemistry (IHC) staining of paraffin-embedded renal tissues was performed to validate the accuracy of the bioinformatic results. Results A total of 1204 DEGs were identified, from which 162 EP-DEGs were further characterized by overlapping with extracellular protein gene lists. From the PPI network analysis, five EP-DEGs (e.g., TNF, COL1A1, FN1, MMP9, and TGFB1) were identified as candidate biomarkers. TNF, COL1A1, and MMP9 had a high diagnostic accuracy for DN. Assessment of immune cell infiltration revealed that the expression of TNF was positively associated with resting dendritic cells (DCs) (r = 0.85, P

Abstract Weight-adjusted waist index (WWI) is a new marker of central obesity. This study explored the association of WWI with all-cause and cardiovascular disease (CVD) mortality in individuals with diabetes or prediabetes. 6551 participants with diabetes or prediabetes from the National Health and Nutrition Examination Survey (NHANES) records between 2005 and 2018 were included. The association of WWI with all-cause and CVD mortality was assessed using Kaplan-Meier survival analysis, Cox proportional hazards model (Cox regression), and restricted cubic spline (RCS). The predictive value of WWI for mortality was analyzed using time-dependent receiver operating characteristic curves (ROC). There were 1083 all-cause deaths and 360 CVD deaths. Multivariable-adjusted Cox regression analyses showed WWI was positively correlated with the risk of all-cause and CVD mortality in subjects with diabetes or prediabetes. Multivariate-adjusted RCS analyses showed a linear and positive correlation of WWI with all-cause mortality risk, and a nonlinear relationship with CVD mortality, with a threshold of 12.35. The area under the curve (AUC) for 3, 5, and 10-years survival for all-cause mortality was 0.795, 0.792, and 0.812, respectively, and for CVD mortality was 0.815, 0.833, and 0.831, respectively. WWI is a valuable predictor of all-cause mortality risk in patients with diabetes and prediabetes, and a valuable predictor of CVD mortality risk when patients with diabetes and prediabetes are considered as a whole.

Abstract. Along with the surge of unearthed medical literature and cultural relics in recent years, a network of channels in the system of medical conduit vessels (meridians) during the early Western Han dynasty has become much clearer gradually. In it, the increasing number of channel branches, network vessels and needle insertion holes (acupoints) is an important feature of the development of channel medicine during the Western Han dynasty. This is not only a reflection of the expanding requirements of the theoretical system of the main trunk channels and other vessels, but also an inevitable result of the continuous enrichment and accumulation of clinical experience. This article integrates the information about channel branches, network vessels, inscriptions, dots and further relics on the Tianhui (天回) Lacquered Meridian Figurine to compare the unearthed literature of the channel genre with the transmitted classical literature about acupuncture. The “Heart-Regulated Channel” in Medical Manuscripts on Bamboo Slips from Tianhui (《天回医简》) serves as an example to explain the occurrence, development and changes of the channel branches and network vessels in the early system of medical channels.

Deep learning technologies have revolutionized the management of energy, energy consumption, and data security within smart grids through non-intrusive load monitoring (NILM). This paper explores the use of deep learning for real-time intrusion detection in power grids with a primary focus on safeguarding the integrity and security of Data Processing Units (DPUs). An evaluation of various machine learning models, including Support Vector Machine (SVM), Linear Discriminant Analysis (LDA), Decision Trees, and Random Forests, is conducted to detect various types of intrusions, including Fault, Injection, Masquerade, Normal, and Replay. Random Forest produced AUC values of 1.00 for all classes and an overall F1-score of 0.99 for all classes. The Decision Tree model also shows robust performance for detecting Fault and Injection intrusions (AUC = 0.98), with an overall F1-score of 0.94. However, the LDA and SVM models do not perform well in detecting Injection intrusions with overall F1-scores of 0.83 and 0.86. Advances in machine learning can be used to improve smart grid security, reliability, and efficiency, according to this study. These findings highlight the potential of advanced machine learning techniques to enhance smart grid reliability and efficiency. Doi: 10.28991/HIJ-2024-05-03-018 Full Text: PDF

Abstract The objective of this study is to investigate the association between diabetic kidney disease (DKD) and various adiposity indexes, including the visceral adiposity index (VAI), lipid accumulation product index (LAPI), visceral fat area (VFA), and subcutaneous fat area (SFA) in type 2 diabetes mellitus (T2DM) patients. 1176 T2DM patients was stratified into normoalbuminuria (NO), microalbuminuria (MI), and macroalbuminuria (MA) groups based on their urinary albumin-creatinine ratio (UACR) levels. To analyse the correlation between DKD and VAI, LAPI, VFA, and SFA. Multiple linear, restricted cubic spline (RCS), subgroup analyses, and multinomial logistic regression were employed. After adjusting for confounding variables, UACR levels were positively associated with VAI, LAPI, and VFA. RCS curves demonstrated a J-shaped dose-response relationship between VAI and LAPI levels with UACR levels, while a linear correlation was observed between UACR levels and VFA. Using the NO and MI as reference groups, the MA group was analysed as the observational group. DKD severity was positively associated with VAI, LAPI and VFA. When evaluating DKD prognostic risk, with the low-risk and medium-risk groups serving as reference categories, a significant positive correlation was identified with prognostic risk and VAI, LAPI, and VFA in the high-risk or very high-risk groups. In patients with T2DM, DKD severity and prognostic risk were positively correlated with VAI, LAPI, and VFA levels.

Abstract Piercing-sucking pests are the most notorious group of pests for global agriculture. RNAi-mediated crop protection by foliar application is a promising approach in field trials. However, the effect of this approach on piercing-sucking pests is far from satisfactory due to the limited uptake and transport of double strand RNA (dsRNA) in plants. Therefore, there is an urgent need for more feasible and biocompatible dsRNA delivery approaches to better control piercing-sucking pests. Here, we report that foliar application of layered double hydroxide (LDH)-loaded dsRNA can effectively disrupt Panonychus citri at multiple developmental stages. MgAl-LDH-dsRNA targeting Chitinase (Chit) gene significantly promoted the RNAi efficiency and then increased the mortality of P. citri nymphs by enhancing dsRNA stability in gut, promoting the adhesion of dsRNA onto leaf surface, facilitating dsRNA internalization into leaf cells, and delivering dsRNA from the stem to the leaf via the vascular system of pomelo plants. Finally, this delivery pathway based on other metal elements such as iron (MgFe-LDH) was also found to significantly improve the protection against P. citri and the nymphs or larvae of Diaphorina citri and Aphis gossypii, two other important piercing-sucking hemipeteran pests, indicating the universality of nanoparticles LDH in promoting the RNAi efficiency and mortality of piercing-sucking pests. Collectively, this study provides insights into the synergistic mechanism for nano-dsRNA systemic translocation in plants, and proposes a potential eco-friendly control strategy for piercing-sucking pests. Graphical Abstract

Plasma arc additive manufacturing (PAAM) was applied to fabricate TC4 and Ti48Al (gamma titanium aluminide) bimetals in this work. The impact of deposition sequence on the microstructure and mechanical properties of two groups of bimetals (TC4-Ti48Al, first deposited TC4, then Ti48Al; Ti48Al-TC4, first deposited Ti48Al, then TC4) was investigated. The results show that the ultimate tensile strengths of two groups of bimetals exhibit significant differences, with 158.4 MPa for TC4-Ti48Al and 232.3 MPa for Ti48Al-TC4, the reason for this disparity is the difference in microstructure at the transition zone, which is attributed to heat input and Marangoni convection. The phase transformation evolution of TC4-Ti48Al transition zone is (major α2 + minor α)→ (major α2 + minor γ) → (major γ + minor α2), and (major α2 + minor α) → (major α + minor α2) for Ti48Al-TC4. The formation mechanism of transition zones and relationship between the microstructure characteristics and mechanical properties of two groups of bimetals were further discussed. Overall, the property of Ti48Al-TC4 was superior, and this work provides a promising new method for the preparation of TC4 and Ti48Al bimetals.

According to the requirements of the pre-assessment service and earthquake emergency disposal, we collected the pre-assessment survey data of Sichuan in recent ten years, and designed the database structure with deeply mining, classification and coding. At last, we established the database for pre-assessment survey data to realize fast query of pre-assessment survey data, statistics, calls and other functions, which promoting the transformation of pre-assessment achievements. And it also realizes the scientific, standardized and systematic management of pre-assessment survey data, and provides data guarantee for earthquake disaster risk management and earthquake emergency information services.

Abstract Background The prognostic potential of immune-related genes, particularly immune checkpoint inhibitors (ICIs) and long non-coding RNAs (lncRNAs), is gaining attention for evaluating the prognosis of breast cancer patients. Methods We analyzed 23 datasets to identify 15 ICI-related mRNAs and 5 immune-related lncRNAs, creating a robust immune score (IS). This score was used to classify patients into high and low IS groups and assess their survival outcomes. Results Patients with high IS showed significantly poorer overall survival (OS) and progression-free survival (PFS) compared to those with low IS. Multivariate Cox regression analysis confirmed IS as an independent prognostic factor. Additionally, high IS was associated with higher mutation loads and neoantigen profiles, while low IS correlated with enhanced immune cell infiltration. Conclusions The immune score developed from ICI-related mRNAs and lncRNAs effectively predicts the prognosis of breast cancer patients and highlights the differential immune and inflammatory responses between patients with varying levels of immune score. This underscores the relevance of IS in guiding therapeutic decisions and tailoring patient management strategies in clinical settings.

Abstract. Background:. Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants. Methods:. A total of 3053 healthy Han Chinese adults (1922 women) aged 18–79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere–Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance. Results:. All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction

Background: The limited curative effect of PD-L1/PD-1 blockades presents challenges to immunotherapy for advanced gastric cancer. We have found that methionine restriction (MR) enhances the drug resistance of gastric carcinoma cells. We aimed to explore whether MR can enhance the efficacy of PD-L1/PD-1 blockades in gastric cancer. Methods: To conduct MR, gastric carcinoma cells were transfected with LV-METase in vitro, and 615 mice were injected with MFC cells with stable METase expression in vivo. Flow cytometry was conducted to measure the proportions of M1/M2 macrophages and CD8+ GZMB+/IFN-γ+ T cells. Additionally, the levels of M1/M2 macrophage markers and MIF were also detected. Results: MR increased M1 and down-regulated M2 macrophages. MR suppressed MIF levels in gastric carcinoma cells, while the addition of anti-MIF neutralizing antibody inhibited the effect of MR on macrophage M1/M2 polarization. MR enhanced the increase of the proportion of CD8+ GZMB+ T cells and CD8+ IFN-γ+ T cells induced by PD-L1/PD-1 blockades. In vivo detection verified the efficacy of the combination of MR and PD-L1/PD-1 blockades on gastric cancer. Conclusions: MR inhibits the secretion of MIF by gastric carcinoma cells, promotes macrophage M1 polarization, and enhances the therapeutic effect of PD-L1/PD-1 blockades in gastric cancer.

Common carp (Cyprinus carpio), an economically important freshwater fish species, is worldwide farmed especially in Europe and Asia. The current high-density intensive rearing way leading to a high susceptibility to various pathogens, and Aeromonas hydrophila is one of the most frequently encountered bacteria, causing huge economic losses to the common carp industry. The mucosal barrier of fish constitutes the first line of defense against various pathogens, and some level of inter-connectivity exists among teleost mucosal tissues. However, the molecular basis for a common mucosal immune response at multiple sites or response at one site but during different timepoints following stimulation remains to be studied. In this study, we examined and systematically analyzed a total of 144 transcriptome files from three primary common carp mucosal tissues at four early timepoints following the infection of A. hydrophila. A total of 410 unigenes were significantly differentially expressed in all tested mucosal tissues. Through GO enrichment and KEGG pathway analysis, 28 key genes which might played critical roles in the common mucosal immune response of common carp during the early stage of bacterial infection were identified. Further WGCNA analysis showed that, besides the common response, three mucosal tissues exhibited tissue-specific gene regulatory network. Meanwhile, candidate hub genes in each tissue were identified, including trim3, rpl14, tln2, itpr1, and others. Our results will provide a fundamental basis for understanding the molecular mechanisms of teleost mucosal immunity, and might suggest strategies for developing novel teleost mucosal vaccines in aquaculture.

Curative resection stands as the sole potential cure for gallbladder cancer (GBC); nevertheless, a dearth of knowledge persists regarding long-term follow-up data and prognostic factors that hinder achieving a cure post-surgery. A retrospective cohort study was conducted by analyzing pathologically confirmed initial resections for GBC between 2000 and 2013 across three Chinese medical centers. The concept of observed cure refers to a 10-year survival period devoid of any disease recurrence. Employing a semiparametric proportional hazards mixture cure model enabled the identification of clinicopathological factors impeding a cure for GBC post-surgery. In our current study, a total of 331 patients were included, with a follow-up period exceeding a decade. The median overall survival (OS) was recorded at 31.6 months, with 39 patients (11.78%) achieving a 10-year OS, classified as 10-year survivors. Within this subset, 36 patients reached a 10-year relapse-free survival, denoting cure, and yielding an observed cure rate of 10.88%. Notably, factors such as combined surgical resection involving invaded organs, positive lymph node metastasis, and R1 resection (below 1%) were identified as virtually precluding a cure. Additionally, patients with T3–4 stage, hepatic invasion, advanced AJCC stage or poor tumor differentiation exhibited a low likelihood of achieving cure (below 5%). The discovery of these prognostic factors holds significant value in tailoring individualized treatment strategies and enhancing clinical decision-making processes.

Common carp is a globally farmed and economically important freshwater fish species. Due to the intensive culture conditions, the farmed common carp are susceptible to various pathogens, causing high mortality and serious economic losses to the carp culture industry. The route of infection is usually through the main mucosal tissues. In order to generate an effective strategy to better manage the fish disease, it is important to understand mucosal immune related genes as well as their expressions during infection. In this study, the common carp mucin gene family were identified and characterized through bioinformatics analysis, and their expression patterns were examined in healthy tissues of common carp as well as the mucosal tissues after the infection of Aeromonas hydrophila. Our results showed that, there were a set of 11 mucin genes across the entire common carp genome. Functional domain prediction and phylogenetic analysis supported their annotation and orthologies. Examining gene copy number across several vertebrates showed that muc4 and muc6 genes were present in other vertebrate, but were lost in teleost fish, which appeared as a result of gene loss after the split of teleost fish from tetrapods during evolution. The mucin genes presented tissue-specific expression patterns in various healthy common carp tissues, with relatively high expression levels in mucosal tissues, indicating their important roles likely in mucosal immune response. Furthermore, the expression of all mucin genes except for muc2-1 were significantly regulated at one or more timepoints in minimum one mucosal tissue after bacterial infection, suggesting that the mucin gene family played critical roles in the mucosal immunity of common carp in response to pathogenic invasion. Collectively, our findings provided fundamental genomic resources for better understanding the vital roles of mucin genes in the defense against pathogen invasion in teleost.

Background: Anhedonia is a deficit of dynamic reward process, and a large proportion of schizophrenia patients continue to experience anhedonia even during the stable phase. However, few studies have examined the multiple aspects of performance in reward processing in patients with stable schizophrenia and evidence suggests that physical and cognitive effort may involve different neural mechanisms. Methods: Parallel measures of effort-based expenditure for reward tasks (EEfRT) and self-report questionnaires of pleasure were applied in 61 patients with stable schizophrenia (SSZ) and 46 healthy controls (HCs), and percentages of hard task choices (HTC%) were used to assess motivation in reward processing. Negative symptoms, neurocognitive and social function were evaluated in SSZ patients, and associations with performance in reward tasks were explored. Results: SSZ patients reported more severe consummatory and anticipatory anhedonia and social anhedonia. HTC% in reward tasks of SSZ patients were significantly lower than that of HCs, especially in cognitive-effort tasks. HTC% in cognitive tasks were correlated with motivation and pleasure dimension of negative symptoms, whereas HTC% in physical tasks were associated with expression dimension. Anticipatory anhedonia and negative symptoms were correlated with Personal and Social Performance Scale (PSP) scores. Conclusion: Patients with stable schizophrenia have social anhedonia, physically consummatory and anticipatory anhedonia and reduced reward motivation. They are less willing to make cognitive effort than physical effort for reward. The different associations of physical and cognitive effort with negative symptoms indicate physical and cognitive effort may represent disparate neuropsychological processes. Anticipatory anhedonia is closely related to social functioning.

In the field of emotion recognition, analyzing emotions from speech alone (single-modal speech emotion recognition) has several limitations, including limited data volume and low accuracy. Additionally, single-task models lack generalization and fail to fully utilize relevant information. To address these issues, this paper proposes a new bi-modal bi-task emotion recognition model. The proposed model introduces multi-task learning on the Transformer architecture. On one hand, unsupervised contrastive predictive coding is used to extract denser features from the data while preserving self-information and context-related information. On the other hand, model robustness against interfering information is enhanced by employing self-supervised contrastive learning. Furthermore, the proposed model utilizes a modality fusion module to incorporate textual and audio information to implicitly align features from both modalities. The proposed model achieved accuracy rates of 82.3% and 83.5% on the IEMOCAP and RAVDESS datasets, respectively, when considering weighted accuracy (WA). When weight is not considered (unweighted accuracy (UA)), the model achieved 83.0% and 82.4% accuracy. Compared to the existing methods, the performance is further improved.

ABSTRACTUrinary tract infections (UTIs) are among the most common late-onset infections in preterm infants, characterized by nonspecific symptoms and a pathogenic spectrum that diverges from that of term infants and older children, which present unique diagnostic and therapeutic challenges. Existing data on the role of gut microbiota in UTI pathogenesis in this demographic are limited. This study aims to investigate alterations in gut microbiota and fecal calprotectin levels and their association with the development of UTIs in hospitalized preterm infants. A longitudinal case-control study was conducted involving preterm infants admitted between January 2018 and October 2020. Fecal samples were collected weekly and analyzed for microbial profiles and calprotectin levels. Propensity score matching, accounting for key perinatal factors including age and antibiotic use, was utilized to match samples from UTI-diagnosed infants to those from non-UTI counterparts. Among the 151 preterm infants studied, 53 were diagnosed with a UTI, predominantly caused by Enterobacteriaceae (79.3%) and Enterococcaceae (19.0%). Infants with UTIs showed a significantly higher abundance of these families compared to non-UTI infants, for both Gram-negative and positive pathogens, respectively. Notably, there was a significant pre-UTI increase in the abundance of pathogen-specific taxa in infants later diagnosed with UTIs, offering high predictive value for early detection. Shotgun metagenomic sequencing further confirmed the dominance of specific pathogenic species pre-UTI and revealed altered virulence factor profiles associated with Klebsiella aerogenes and Escherichia coli infections. Additionally, a decline in fecal calprotectin levels was observed preceding UTI onset, particularly in cases involving Enterobacteriaceae. The observed pathogen-specific alterations in the gut microbiota preceding UTI onset offer novel insight into the UTI pathogenesis and promising early biomarkers for UTIs in preterm infants, potentially enhancing the timely management of this common infection. However, further validation in larger cohorts is essential to confirm these findings.

Background and purposeTriggering receptor expressed on myeloid cells-1 (TREM-1) was reported to be critical for mediating the neurological function after stroke, while the impact of soluble TREM-1 (sTREM-1) on cognitive impairment after ischemic stroke is unclear. We aimed to explore the association between sTREM-1 and post-stroke cognitive impairment (PSCI).MethodsWe prospectively recruited consecutive ischemic stroke patients who admitted hospital within 7 days of onset. Serum sTREM-1 concentrations were measured after admission. Cognitive function was assessed at 90 days follow-up using the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). PSCI was defined as a MMSE score of

ObjectiveThis study aims to investigate the effects of pectin-degrading bacteria on the microbial community and physicochemical properties during the fermentation process of cigar tobacco, evaluating its potential in reducing green bitterness and enhancing aroma.MethodsBy isolating and screening pectin-degrading bacteria, high-throughput sequencing and physicochemical analysis were employed to compare the microbial flora and physicochemical component differences in different treatment groups of cigar tobacco. Furthermore, correlation analysis was performed to examine the relationships between these variables.ResultsThe results showed that the strains YX-2 and DM-3, isolated from the cigar tobacco variety “Yunxue No. 1,” exhibited strong pectin-degrading abilities. Phylogenetic analysis revealed that strain YX-2 is highly homologous to Bacillus flexus, while strain DM-3 is highly homologous to Bacillus siamensis. After fermentation, the addition of strains YX-2 and DM-3 significantly reduced the pectin content in the tobacco leaves, increased the total sugar and reducing sugar content, reduced green bitterness, and markedly enhanced the total aroma components. Notably, DM-3 exhibited outstanding performance in the production of Maillard reaction products. Microbial community analysis showed that the addition of pectin-degrading bacteria significantly increased the diversity of both bacteria and fungi, especially in the TDM3 group, where the relative abundance of Pseudomonas was notably elevated. Correlation analysis revealed that Pseudomonas had a significant positive correlation with both reducing sugar and total sugar, and a significant negative correlation with pectin, indicating its important role in sugar metabolism and pectin degradation. Additionally, fungal genera such as Cercospora were significantly negatively correlated with total sugar and total nitrogen, while Eurotium was closely associated with pectin degradation and reducing sugar accumulation.ConclusionThis study found that the addition of Pectin-degrading bacteria YX-2 and DM-3 significantly optimized the microbial community structure during the cigar tobacco fermentation process and improved the physicochemical properties of the tobacco leaves, with notable effects in reducing green bitterness and enhancing aroma.

Abstract Background The high prevalence of diabetic kidney disease (DKD) in the United States necessitates further investigation into its impact on complications associated with total hip arthroplasty (THA). This study utilizes a large nationwide database to explore risk factors in DKD cases undergoing THA. Methods This research utilized a case–control design, leveraging data from the national inpatient sample for the years 2016 to 2019. Employing propensity score matching (PSM), patients diagnosed with DKD were paired on a 1:1 basis with individuals free of DKD, ensuring equivalent age, sex, race, Elixhauser Comorbidity Index (ECI), and insurance coverage. Subsequently, comparisons were drawn between these PSM-matched cohorts, examining their characteristics and the incidence of post-THA complications. Multivariate logistic regression analysis was then employed to evaluate the risk of early complications after surgery. Results DKD's prevalence in the THA cohort was 2.38%. A 7-year age gap separated DKD and non-DKD patients (74 vs. 67 years, P

Abstract Objective Retinal vascular endothelial cell (RVECs) injury is a major cause of morbidity and mortality among the patients with diabetes. RVECs dysfunction is the predominant pathological manifestation of vascular complication in diabetic retinopathy. N6-methyladenosine (m6A) serves as the most prevalent modification in eukaryotic mRNAs. However, the role of m6A RNA modification in RVECs dysfunction is still unclear. Methods RT-qPCR analysis and western blot were conducted to detect the change of m6A RNA modification in diabetic retinopathy. CCK-8 assay, transwell experiment, wound healing assay, tube formation experiment, m6A-IP-qPCR were performed to determine the role of YTHDC1 in RVECs. Retinal trypsin digestion test and H&E staining were used to evaluate histopathological changes. Results The levels of m6A RNA methylation were significantly up-regulated in HG-induced RVECs, which were caused by increased expression of YTHDC1. YTHDC1 regulated the viability, proliferation, migration and tube formation ability in vitro. YTHDC1 overexpression impaired RVECs function by repressing CDK6 expression, which was mediated by YTHDC1-dependent mRNA decay. Moreover, it showed sh-YTHDC1 inhibited CDK6 nuclear export. Sh-YTHDC1 promotes the mRNA degradation of CDK6 in the nucleus but does not affect the cytoplasmic CDK6 mRNA. In vivo experiments showed that overexpression of CDK6 reversed the protective effect of sh-YTHDC1 on STZ-induced retinal tissue damage. Conclusion YTHDC1-mediated m6A methylation regulates diabetes-induced RVECs dysfunction. YTHDC1-CDK6 signaling axis could be therapeutically targeted for treating DR.

Abstract Background Currently, treatment regimens for visceral leishmaniasis (VL) are limited because of the presence of numerous adverse effects. Nicotinamide, a readily available and cost-effective vitamin, has been widely acknowledged for its safety profile. Several studies have demonstrated the anti-leishmanial effects of nicotinamide in vitro. However, the potential role of nicotinamide in Leishmania infection in vivo remains elusive. Methods In this study, we assessed the efficacy of nicotinamide as a therapeutic intervention for VL caused by Leishmania infantum in an experimental mouse model and investigated its underlying molecular mechanisms. The potential molecular mechanism was explored through cytokine analysis, examination of spleen lymphocyte subsets, liver RNA-seq analysis, and pathway validation. Results Compared to the infection group, the group treated with nicotinamide demonstrated significant amelioration of hepatosplenomegaly and recovery from liver pathological damage. The NAM group exhibited parasite reduction rates of 79.7% in the liver and 86.7% in the spleen, respectively. Nicotinamide treatment significantly reduced the activation of excessive immune response in infected mice, thereby mitigating hepatosplenomegaly and injury. Furthermore, nicotinamide treatment enhanced fatty acid β-oxidation by upregulating key enzymes to maintain lipid homeostasis. Conclusions Our findings provide initial evidence supporting the safety and therapeutic efficacy of nicotinamide in the treatment of Leishmania infection in BALB/c mice, suggesting its potential as a viable drug for VL. Graphical Abstract

In this study, a novel three-dimensional biofilm electrode reactor (3D-BER) with a graphene oxide (GO)–modified cathode was developed to enhance the denitrification performance of secondary effluent from wastewater treatment plants (SEWTPs). The effects of different hydraulic retention times (HRTs) and currents on the 3D-BER were explored. The results indicated that at the optimal HRT of 4 h and current of 350 mA/m2, the 3D-BER with GO-modified cathode had a higher denitrification rate (2.40 ± 0.1 mg TN/L/h) and less accumulation of intermediate products, especially with 3.34% total nitrogen (TN) molar conversion to N2O. The GO-modified cathode offered a large biocompatible specific surface area and enhanced the conductivity, which favored microbial growth and increased electron transfer efficiency and extracellular enzyme activities. Moreover, the activity of nitrite reductase increased more than that of nitrate reductase to accelerate nitrite reduction, thus facilitating the denitrification process. The proposed 3D-BER provided an effective solution to elevate tertiary denitrification in the SEWTP. HIGHLIGHTS Secondary effluent from wastewater treatment plants are treated by the three-dimensional biofilm electrode reactor (3D-BER) with GO-modified cathode.; The 3D-BER improves the denitrification efficiency at appropriate current and HRT.; A 52.6% N2O greenhouse gas reduction with 3.34% TN molar conversion to N2O was achieved.; The GO-modified 3D-BER enhances denitrifying enzyme activity.;

Background: The paclitaxel liposome formulation, encapsulating paclitaxel within a phospholipid bilayer, addresses the insolubility of traditional paclitaxel formulations, thereby reducing toxicity without compromising its antitumor efficacy. Methods: This multicenter, open-label, non-inferiority randomized controlled trial (ChiCTR2000038555) evaluates the efficacy and safety of paclitaxel liposome in comparison to the standard regimen of paclitaxel combined with carboplatin (PLC vs. PC) as first-line therapy in patients with epithelial ovarian cancer. Results: An analysis of median progression-free survival (PFS) revealed non-inferior outcomes between 263 patients in the PLC group and 260 patients in the PC group (32.3 vs. 29.9 months, hazard ratio [HR], 0.89 [95% CI, 0.64−1.25]), using a non-inferior margin of 1.3. Although the overall incidence of treatment-related adverse events was comparable between groups, the PLC group experienced significantly fewer non-hematologic toxicities than those treated with the PC regimen. Conclusion: The findings affirm the non-inferiority of paclitaxel liposome compared to the combination of paclitaxel and carboplatin regarding therapeutic efficacy, with an enhanced safety profile marked by reduced non-hematologic toxicities.

Abstract Objective To compare the effect of different indicators on stress‐induced hyperglycemia for predicting in‐hospital outcomes of acute intracerebral hemorrhage. Methods Using data from the Chinese Stroke Center Alliance database, which is a national, multicenter, prospective, and consecutive program. Stress‐induced hyperglycemia was described as glycemic gap (GG, defined as fasting blood glucose [FBG] minus estimated average blood glucose) and stress hyperglycemia ratio (SHR, defined as FBG‐to‐estimated average blood glucose ratio [SHR 1] or FBG‐to‐HbA1c ratio [SHR 2]). The primary outcome was in‐hospital mortality, and the second outcome was hematoma expansion. Results A total of 71,333 patients with acute intracerebral hemorrhage were included. In multivariate analyses, the highest levels of GG (OR 1.68, 95% CI 1.12–2.51), SHR 1 (OR 1.73, 95% CI 1.15–2.60), and SHR 2 (OR 2.07, 95% CI 1.33–3.23) were associated with in‐hospital death (all the p trends 0.05) was related to hematoma expansion. No association between GG or SHR 1 and hematoma expansion was observed. The areas under the ROC curve of GG, SHR 1, and SHR 2 for in‐hospital mortality were 0.8808 (95% CI 0.8603–0.9014), 0.8796 (95% CI 0.8589–0.9002), and 0.8806 (95% CI 0.8600–0.9012). The areas under the ROC curve of SHR 2 for hematoma expansion were 0.7133 (95% CI 0.6964–0.7302). Interpretation SHR (FBG‐to‐HbA1c ratio) was associated with both in‐hospital death and hematoma expansion in intracerebral hemorrhage, and might serve as an accessory indicator for the in‐hospital prognosis of intracerebral hemorrhage.

Abstract When single-particle dynamics are suppressed in certain strongly correlated systems, dipoles arise as elementary carriers of quantum kinetics. These dipoles can further condense, providing physicists with a rich realm to study fracton phases of matter. Whereas recent theoretical discoveries have shown that an unconventional lattice model may host a dipole condensate as the ground state, we show that dipole condensates prevail in bosonic systems due to a self-proximity effect. Our findings allow experimentalists to manipulate the phase of a dipole condensate and deliver dipolar Josephson effects, where supercurrents of dipoles arise in the absence of particle flows. The self-proximity effects can also be utilized to produce a generic multipolar condensate. The kinetics of the n-th order multipoles unavoidably creates a condensate of the (n + 1)-th order multipoles, forming a hierarchy of multipolar condensates that will offer physicists a whole new class of macroscopic quantum phenomena.

Abstract Background The main purpose of this paper is to introduce a method that can accurately locate the posterior capsule of the lens to facilitate a relatively complete resection of the anterior vitreous body. Methods A total of 51 patients in the experimental group and control group were enrolled in this study. Phacoemulsification combined with vitrectomy was performed in all cases. After the cataract procedure was completed in the control group, the surgeon performed a conventional anterior vitrectomy with the operative eye. In the experimental group, anterior vitrectomy was performed according to the threadiness corrugation of the posterior capsule of the lens. During the operation, with the help of triamcinolone, two surgeons confirmed the resection of the anterior vitreous cortex; the best corrected visual acuity and intraocular pressure of all patients were recorded at 1 week, 1 month and 3 months after surgery. Results Fifty patients underwent phacoemulsification combined with vitrectomy, except one patient in the experimental group who was lost to follow-up. After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. There was no significant difference in preoperative visual acuity between the two groups (t = 0.83, P = 0.25). Both groups had varying degrees of improvement in best corrected visual acuity at 1 week, 1 month and 3 months after surgery. Moreover, there was no significant difference in BCVA between the two groups at the three follow-up time points (t=-1.15, -1.65, -1.09, P = 0.53, 0.21, 0.23). After surgery, no significant complications were observed in all patients except two patients in the control group with temporary increases in intraocular pressure. Incomplete resection of the anterior vitreous cortex was observed in 2 patients in each group, but there was no significant difference (χ2 = 7.81, P > 0.05). Conclusion In the process of cataract surgery combined with vitrectomy, thready corrugation appears in the posterior capsule of the lens and is an important sign of its localization. Anterior vitrectomy can be accomplished safely and effectively with the help of thread-like corrugation, and the surgical effect is almost the same as that of traditional surgery. Especially suitable for beginners in vitreous surgery.

Abstract Background The prospective phase III multi-centre L-MOCA trial (NCT03534453) has demonstrated the encouraging efficacy and manageable safety profile of olaparib maintenance therapy in the Asian (mainly Chinese) patients with platinum-sensitive relapsed ovarian cancer (PSROC). In this study, we report the preplanned exploratory biomarker analysis of the L-MOCA trial, which investigated the effects of homologous recombination deficiency (HRD) and programmed cell death ligand 1 (PD-L1) expression on olaparib efficacy. Methods HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan–Meier method was utilised to analyse progression-free survival (PFS). Results This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5–22.1) versus 9.2 months (95% CI: 7.5–13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4–18.2) versus 22.2 months (95% CI: 18.3–NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9–NA) versus 8.3 months (95% CI: 6.7–13.8)]. Conclusions HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2. Trial registration NCT03534453. Registered at May 23, 2018.

Background: Association of Coronavirus disease 2019 vaccines with thrombosis has raised concerns among patients with coronary atherosclerosis disease (CAD). Objectives: After vaccination against SARS-CoV-2, to detect thrombosis formation in atherosclerosis ApoE−/− mice, and platelet activation, coagulation, the profile of prothrombotic antibodies, and the production of platelet factor 4 (PF4) antibodies in patients with CAD. Methods: Atherosclerotic ApoE−/− mice were immunized with saline or inactivated SARS-CoV vaccines. We investigated FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo. Inpatients undergoing percutaneous coronary intervention (PCI) were consecutively enrolled and defined according to vaccination status. We evaluated coagulation by thrombelastograph (TEG), platelet activation makers by flow cytometry, PF4 antibody and antiphospholipid antibodies by ELISA, and SARS-CoV-2 neutralizing antibody. Results: In atherosclerotic ApoE−/− mice, FeCl3-induced thrombus formation and thrombus formation under flow conditions were similar between saline-treated and inactivated SARS-CoV-2 vaccines-treated groups. A total of 182 patients undergoing PCI were included in the final analysis, of whom 92 had been vaccinated. Baseline characteristics were well balanced between unvaccinated and vaccinated groups. The expression of PAC-1 and P-selectin, the prevalence of positivity for PF4 antibodies and antiphospholipid antibodies were similar between these two groups. Conclusions: Inactivated SARS-CoV-2 vaccines did not potentiate thrombosis formation in atherosclerotic mice. Inactivated SARS-CoV-2 vaccines did not enhance platelet activation, or trigger the production of PF4 and antiphospholipid antibodies in patients with CAD. In light of the observed thrombotic risks associated with adenovirus-based COVID-19 vaccines, inactivated vaccines may offer a potentially safer option for individuals with CAD.

Persistent infection with high-risk human papillomavirus (HR-HPV) is the main cause of cervical cancer. These chronic infections are characterized by high expression of the HPV E6 and E7 oncogenes and the absence of the L1 and L2 capsid proteins. The regulation of HPV gene expression plays a crucial role in both the viral life cycle and rare oncogenic events. Alternative splicing of HPV mRNA is a key mechanism in post-transcriptional regulation. Through alternative splicing, HPV mRNA is diversified into various splice isoforms with distinct coding potentials, encoding multiple proteins and influencing the expression of HPV genes. The spliced mRNAs derived from a donor splicing site within the E6 ORF and one of the different acceptor sites located in the early mRNA contain E6 truncated mRNAs, named E6*. E6* is one of the extensively studied splicing isoforms. However, the role of E6* proteins in cancer progression remains controversial. Here, we reviewed and compared the alternative splicing events occurring in the genomes of HR-HPV and LR-HPV. Recently, new HPV alternative splicing regulatory proteins have been continuously discovered, and we have updated the regulation of HPV alternative splicing. In addition, we summarized the functions of known splice isoforms from three aspects: anti-tumorigenic, tumorigenic, and other cancer-related functions, including not only E6*, but also E6^E7, E8^E2, and so on. Comprehending their contributions to cancer development enhances insights into the carcinogenic mechanisms of HPV and explores the potential utility of alternative splicing in the diagnosis and treatment of cervical cancer.

Krylov complexity has emerged as a probe of operator growth in a wide range of nonequilibrium quantum dynamics. However, a fundamental issue remains in such studies: the definition of the distance between basis states in Krylov space is ambiguous. Here we show that Krylov complexity can be rigorously established from circuit complexity when dynamical symmetries exist. Whereas circuit complexity characterizes the geodesic distance in a multidimensional operator space, Krylov complexity measures the height of the final operator in a particular direction. The geometric representation of circuit complexity thus unambiguously designates the distance between basis states in Krylov space. This geometric approach also applies to time-dependent Liouvillian superoperators, where a single Krylov complexity is no longer sufficient. Multiple Krylov complexity may be exploited jointly to fully describe operator dynamics.

Objective: This study aimed to explore the potential causal relationship between intraocular pressure (IOP) and myopia. Methods: The study included 3,459 patients who underwent corneal refractive surgery at our institution between 2021 and 2023. Preoperative data on IOP, spherical equivalent (SE), axial length (AL), and corneal thickness (CCT) were collected. The association between IOP and myopia was investigated through rank correlation analysis, and causal inference was examined using Mendelian randomization (MR) methods, including MR-Egger, weighted median, mode-based estimation, simple mode, and inverse variance weighted (IVW) approaches. Utilizing summary statistics from genome-wide association studies (GWAS), IOP was considered as the exposure, with myopia as the outcome variable. IVW method was employed for the primary analysis, supplemented by sensitivity analyses. Results: Cross-sectional analysis revealed a non-significant association between corrected IOP (cIOP) and myopia (r = -0.019, P = 0.12). MR analysis indicated a non-significant genetic causal relationship between cIOP and myopia under the IVW method (OR = 1.001; 95 % CI [0.999–1.003], P = 0.22), a finding corroborated in replication samples (OR = 0.98; 95 % CI [0.96–1.00], P = 0.099). Conclusion: This study did not find a direct causal link between IOP and the development of myopia. These findings challenge the traditional role attributed to IOP in the progression of myopia and highlight the complex, multifactorial process of myopia development. This provides a new perspective on understanding the intricate mechanisms behind myopia progression.

Owing to its tyrosinase inhibitory activity, α-arbutin has been added to several skin care products as a skin-lightening agent. However, the protective effect of α-arbutin against ultraviolet A (UVA)-induced photoaging has not been well investigated. The present study was designed to investigate the photoprotective effect and mechanism of α-arbutin against UVA-induced photoaging. In vitro experiments, HaCaT cells were treated with UVA at a dose of 3 J/cm2 to evaluate the anti-photoaging effect of α-arbutin. α-Arbutin was found to exhibit a strong antioxidant effect by increasing glutathione (GSH) level and inhibiting reactive oxygen species (ROS) production. Meanwhile, α-arbutin markedly improved the expression of sirtuin 3 (SIRT3) and peroxisome proliferator-activated receptor γ coactivator 1 α (PGC-1α) proteins, initiating downstream signaling to increase mitochondrial membrane potential and mediate mitochondrial biogenesis, and improve mitochondrial structure significantly. In vivo analysis, the mice with shaved back hair were irradiated with a cumulative UVA dose of 10 J/cm2 and a cumulative ultraviolet B (UVB) dose of 0.63 J/cm2. The animal experiments demonstrated that α-arbutin increased the expression of SIRT3 and PGC-1α proteins in the back skin of mice, thereby reducing UV-induced skin damage. In conclusion, α-arbutin protects HaCaT cells and mice from UVA damage by regulating SIRT3/PGC-1α signaling pathway.

The Nanhua Basin of South China recorded complete Cryogenian stratigraphic sequence from the Sturtian Glaciation (~717–660 Ma) to the Marinoan Glaciation (~654–635 Ma). The interglacial Datangpo Fm in the Nanhua Basin is divided into two members, and the first member consists of the Mn-carbonate unit and the overlying black shale unit, containing a series of large and superlarge manganese deposits. The metallogenic process of manganese deposits is not clear, and the Mn-carbonates formed through the precursor of Mn-oxide/oxyhydroxide reduction or directly precipitated from an anoxic water column. Moreover, the redox conditions in the deep Nanhua Basin during the precipitation of manganese deposits are also controversial. In this study, the high-resolution nitrogen contents (TN), isotope compositions, carbon isotope compositions of organic and inorganic matter from the first member of the Datangpo Fm are analyzed. The δ15N values of the Mn-carbonate unit (+1.53‰ to +5.26‰, mean +3.36‰) are higher than those of the overlying black shale unit (−3.74‰ to +3.54‰, mean +0.89‰). The Mn contents show a negative relationship with TN but a positive relationship with δ15N in the Mn-carbonate unit, implying that the formation of Mn-carbonates is related to redox variations. The relatively higher δ15N values in the Mn-carbonate unit indicated oxic conditions, and NH4+can be released and partially oxidized during the mineralization of organic matter, resulting in the residual 15N-enriched NH4+ being transferred into clay minerals. Meanwhile, the lower δ15N values in the black shale unit indicated anoxic conditions, which recorded primary N isotope signals. The Mn-carbonate unit is characterized by negative δ13Ccarb values (−11.17‰ to −5.22‰, mean −8.30‰), which show a positive relationship with δ13Corg, but a negative relationship with Mn contents, implying that the negative δ13Ccarb excursions were related to the organic matter degradation during Mn-carbonate formation. The findings of this study indicated that the metallogenesis of manganese deposits in the Cryogenian Nanhua Basin was constrained mainly by the oxic interval in the deep basin. The nitrogen and carbon cycling process can provide new insights into geochemical cycling after the Sturtian Glaciation.

Objectives To compare the level of knowledge of depression, recognition ability and attitudes towards depression among urban and rural residents in Beijing.Design A cross-sectional study.Setting Six districts in Beijing, China, 2021.Participants A total of 6463 participants aged 18 years and above who had lived for more than 6 months over the last year in Beijing were selected in this study.Outcome The awareness and recognition of depression and the views of residents towards people with depression.Results A total of 2554 urban and 2043 rural residents completed the survey. Urban residents of Beijing exhibited a higher average total score on the Depression Knowledge Questionnaire [(20.4±3.3) vs (18.7±3.5), p

ObjectiveTo assess CD276 expression and explore its relationship with the clinicopathological characteristics and prognosis of patients with bladder cancer.MethodsIn total, RNA-sequencing data and clinical profiles of 436 bladder cancer cases from The Cancer Genome Atlas (TCGA) were assessed using the University of California Santa Cruz Xena (UCSC) platform. We compared the CD276 levels in cancerous and adjacent normal tissues and used the R software for statistical association with the clinical stage, grade, and survival (the overall survival, disease-specific survival, and progression-free survival). A single-gene GSEA analysis on TCGA-BLCA data was performed to explore potential pathways through which CD276 might influence bladder cancer. Additionally, CD276 expression was analyzed by comparing data from 9 cancerous tissues and 3 adjacent normal tissues in the GEO dataset GSE7476. Furthermore, we analyzed 133 cancerous bladder and adjacent tissue samples from the Soochow University Hospital, collected between January 1, 2016, and September 30, 2022, to assess the CD276 protein expression using immunohistochemistry. We examined the relationship between tumor CD276 levels and clinical outcomes and prognosis of bladder cancer.ResultsBioinformatic analysis revealed elevated CD276 expression in tumors compared to that in adjacent tissues (p

Specific protein 1 (Sp1) is pivotal in sustaining baseline transcription as well as modulating cell signaling pathways and transcription factors activity. Through interactions with various proteins, especially transcription factors, Sp1 controls the expression of target genes, influencing numerous biological processes. Numerous studies have confirmed Sp1’s significant regulatory role in the pathogenesis of cardiovascular disorders. Post-translational modifications (PTMs) of Sp1, such as phosphorylation, ubiquitination, acetylation, glycosylation, SUMOylation, and S-sulfhydration, can enhance or modify its transcriptional activity and DNA-binding stability. These modifications also regulate Sp1 expression across different cell types. Sp1 is crucial in regulating non-coding gene expression and the activity of proteins in response to pathophysiological stimuli. Understanding Sp1 PTMs advances our knowledge of cell signaling pathways in controlling Sp1 stability during cardiovascular disease onset and progression. It also aids in identifying novel pharmaceutical targets and biomarkers essential for preventing and managing cardiovascular diseases.

Objective: To explore the pharmacological mechanism of the effect of fraxetin in treating acute myeloid leukemia (AML) by the network pharmacology method combined with experimental validation. Methods: The targets of fraxetin were identified through Swisstarget prediction, PhammerMap, and CTDBASE. Disease-related targets of AML were explored using GeneCards and DisGenet databases, and the intersected targets were analyzed in the String website to construct a protein-protein interaction (PPI) network. Subsequently, gene ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were conducted using the DAVID database. Molecular docking of core proteins with drugs was performed using Auto Dock Vina software. Finally, the effect of fraxetin on AML was evaluated by in vitro experiments. The effect of fraxetin on AML cell proliferation was assessed by CCK8, the effect of fraxetin on AML cell apoptosis was assessed by flow cytometry, and the expression of relevant protein targets was detected by Western blotting to evaluate the anti-AML effect of fraxetin. Results: In this study, fraxetin exerts its effect against AML through 101 intersecting genes. The pathway enrichment analysis revealed that the pharmacological effects of fraxetin on AML were related to the Adenosine 5‘-monophosphate (AMP)-activated protein kinase （AMPK） signaling pathway, and the molecular docking results indicated that fraxetin had an excellent binding affinity to both the core target and AMPK. In vitro experiments have demonstrated that fraxetin inhibited the proliferation and induced apoptosis of THP1 and HL60 cells, and the western blotting results indicated that the p-AMPK of the fraxetin intervention group was significantly changed in a dose-dependent manner. Conclusion: Fraxetin may modulate the AMPK signal pathway by interactine with the core target, thereby potentially therapeutic effect on AML.

In the context of hepatocellular carcinoma (HCC) treatment, this study introduces a biomimetic “bomb” approach to target HCC by utilizing macrophages (MAs) as ultrasound-responsive carriers. This advanced biomimetic drug delivery system (MAs-DOX/PFP/Ms, MAs-DPM) encapsulates doxorubicin (DOX) and perfluoropentane (PFP) and is designed to precisely target HCC. MAs-DPM exhibits excellent drug loading capacity and biocompatibility, can effectively release DOX and enhance ultrasound imaging capabilities under ultrasound irradiation (UI). Experiments confirmed that MA maintained its biological activity and vitality during co-incubation and phagocytosis with DOX-loaded DPM, and microscopy confirmed that MA effectively engulfed DPM without changing cell morphology or function. Transwell experiments demonstrated that this bionic “bomb” (MAs-DPMs) not only retained the tumor targeting ability of macrophages, but also successfully delivered therapeutic drugs to tumor cells. Compared with samples without UI treatment, UI significantly increased the release of DOX from MAs-DPM, enhanced the drug release rate and inhibited the growth of HCC cells. Live/Dead staining experiments further intuitively revealed the precise “biobomb” effect of MAs-DPM under UI, effectively proving its ability to inhibit HCC cell proliferation. In vivo studies demonstrated that MAs-DPM was able to proficiently localize tumor sites within 24 h. Furthermore, the ultrasound-mediated phase transition of PFP enhanced the imaging efficacy, confirming the feasibility of macrophage-mimicking biological bombs for real-time in vivo ultrasound tracking. In the tumor-bearing nude mouse model, UI-treated MAs-DPMs remarkably delayed tumor growth and prolonged survival time compared with other groups. Subsequent histological and serum index evaluation further confirmed the in vivo safety of MAs-DPMs, and UI-treatment did not induce significant histological or pathological changes or statistical differences in vital organ or serum markers. These experiment results highlight the great potential of MAs-DPM as a strategic approach for the diagnosis and treatment of HCC.

Integrating multiple hyperspectral linear-array cameras into a Linear-array Multi-camera System (LMS) enables an expanded Field of View (FOV) while preserving high spatial resolution. However, the constrained capabilities of tie points are weakened by the limited overlap and short baseline between sub-cameras, hindering the attainment of reliable solutions for the theoretically ideal relative calibration model. Additionally, the absence of stereoscopic imaging in the LMS introduces the challenge of acquiring dense Ground Control Points (GCPs) throughout the FOV during calibration. In this paper, for calibrating an advanced airborne hyperspectral LMS named Arial Hyperspectral System-1000 (AHS-1000), we propose an equivalent geometric model that transforms the three-camera configuration of the LMS into a single-camera representation on the master camera’s focal plane, which was successfully applied to the data processing system of AHS-1000. We extracted dense GCPs by matching each Level-1 sub-image of the LMS with the bundled images of an existing three-line-scanner aerial image dataset, whose orientation parameters have been accurately solved by bundle adjustment with sparse GCPs; the matched points of each sub-image were consistently projected onto the master focal plane as image observations for our equivalent model. Finally, we established a collinearity equation system and performed a combined strip adjustment to calibrate the distortion terms for each pixel of the equivalent camera. The results demonstrate the effectiveness and robustness of our equivalent modeling method, which outperforms the classic modeling method by 2.83 pixels in interior accuracy and 0.86 pixels in relative accuracy, as well as outperforming another similar equivalent modeling method by 1.22 pixels in interior accuracy and 0.18 pixels in relative accuracy. Additionally, our comparison utilizing bundled images, public DOM (Digital Orthophoto Maps) /DEM (Digital Elevation Models), and high-precision DOM/DEM from aerial three-line-scanner demonstrates that bundled images can achieve higher calibration accuracy.

Abstract Identifying road surface types (paved or unpaved) can ensure road vehicle safety, reduce energy consumption, and promote economic development. Existing studies identified road surface types by using sensors mounted on mobile devices and high-resolution satellite images that are not openly accessible, which makes it difficult to apply them to large-scale (e.g., national or regional) study areas. Addressing this issue, this study developed a dataset of road surface types (paved and unpaved) for the national road network of Kenya, containing 1,267,818 road segments classified as paved or unpaved. To accomplish this, this study proposes a method that integrates crowdsourced geographic data (OpenStreetMap) and Google satellite imagery to identify road surface types. The accuracy, recall, and F1 score of the method were all above 0.94, validating the effectiveness of the method. The data sources of the method are freely available, and the method may be applied to other countries and regions. The dataset developed based on the method can provide data support and decision support for local governments to improve road infrastructure.