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Purpose – Utilizing electrical discharge machining (EDM) to process micro-holes in superalloys may lead to the formation of remelting layers and micro-cracks on the machined surface. This work proposes a method of composite processing of EDM and ultrasonic vibration drilling for machining precision micro-holes in complex positions of superalloys. Design/methodology/approach – A six-axis computer numerical control (CNC) machine tool was developed, whose software control system adopted a real-time control architecture that integrates electrical discharge and ultrasonic vibration drilling. Among them, the CNC system software was developed based on Windows + RTX architecture, which could process the real-time processing state received by the hardware terminal and adjust the processing state. Based on the SoC (System on Chip) technology, an architecture for a pulse generator was developed. The circuit of the pulse generator was designed and implemented. Additionally, a composite mechanical system was engineered for both drilling and EDM. Two sets of control boards were designed for the hardware terminal. One set was the EDM discharge control board, which detected the discharge state and provided the pulse waveform for turning on the transistor. The other was a relay control card based on STM32, which could meet the switch between EDM and ultrasonic vibration, and used the Modbus protocol to communicate with the machining control software. Findings – The mechanical structure of the designed composite machine tool can effectively avoid interference between the EDM spindle and the drilling spindle. The removal rate of the remelting layer on 1.5 mm single crystal superalloys after composite processing can reach over 90%. The average processing time per millimeter was 55 s, and the measured inner surface roughness of the hole was less than 1.6 µm, which realized the micro-hole machining without remelting layer, heat affected zone and micro-cracks in the single crystal superalloy. Originality/value – The test results proved that the key techniques developed in this paper were suite for micro-hole machining of special materials.

Abstract Background With increasing incidence and treatment costs, chronic kidney disease (CKD) has become an important public health problem in China, especially in females. However, the genetic determinants are very limited. The estimated glomerular filtration rate (eGFR) based on creatinine is commonly used as a measure of renal function but can be easily affected by other factors. In contrast, eGFR based on both creatinine and cystatin C (eGFRcr-cys) improved the diagnostic accuracy of CKD. To our knowledge, no genome-wide association analysis of eGFRcr-cys has been conducted in the Chinese population. Methods By conducting a Genome-Wide association study(GWAS), a method used to identify associations between genetic regions (genomes) and traits/diseases, we examined the relationship between genetic factors and eGFRcr-cys in Chinese women, with 1983 participants and 3,838,121 variants included in the final analysis. Result One significant locus (20p11.21) was identified in the Chinese female population, which has been reported to be associated with eGFR based on cystatin C (eGFRcys) in the European population. More importantly, we found two new suggestive loci (1p31.1 and 11q24.2), which have not yet been reported. A total of three single nucleotide polymorphisms were identified as the most important variants in these regions, including rs2405367 (CST3), rs66588571(KRT8P21), and rs626995 (OR8B2). Conclusion We identified 3 loci 20p11.21, 1p31.1, and 11q24.2 to be significantly associated with eGFRcr-cys. These findings and subsequent functional analysis describe new biological clues related to renal function in Chinese women and provide new ideas for the diagnosis and treatment development of CKD.

Abstract Elizabethkingia miricola is a multidrug-resistant pathogen that can cause life-threatening infections in immunocompromised humans and outbreaks in amphibians. However, the specific virulence factors of this microorganism have not been described. In this study, we identified the polysaccharide biosynthesis protein-encoding gene capD, which is located in the conserved region of the Wzy-dependent capsule synthesis gene cluster in the E. miricola strain FL160902, and investigated its role in the pathogenesis of E. miricola. Our results revealed that the capD deletion strain (ΔcapD) lost its typical encapsulated structure, with a 45% reduction in cell wall thickness. CapD affects wza expression in the capsule polysaccharide synthesis pathway. Furthermore, the survival rates were significantly reduced in ΔcapD in response to complement-mediated killing, desiccation stress, and macrophage phagocytosis, whereas biofilm formation, surface hydrophobicity, and adherence to both endothelial and epithelial cells were increased. Additionally, the deletion of capD sharply attenuated the virulence of E. miricola in a frog infection model. Complementation of the capD gene restored the biological properties and virulence to wild-type levels. Overall, these findings suggest that CapD contributes to polysaccharide synthesis and plays a crucial role in the pathogenesis of E. miricola.

Numerous studies have investigated bird diversity-environment relationships in agricultural landscapes. While many studies have emphasized the importance of natural/semi-natural elements and their diversity within or surrounding farmlands, it remains unclear how crop diversity impacts birds. There is also a significant gap in our knowledge regarding the effects of temporal changes in crop composition on bird diversity. Using small farmlands in a sub-tropical city of China, we examined how spatial and temporal variation of crops and other local farmland features was linked to species diversity of birds and their traits. In small peri‑urban agricultural areas of Guangzhou, we collected bird and crop/non-crop data approximately bimonthly from December 2021 to October 2022. Overall crop diversity and seasonal crop changes were indexed by alpha diversity (Shannon-Wiener index) and beta diversity, respectively. Both alpha and beta crop diversities were positively associated with Shannon-Wiener diversity of birds. Alpha crop diversity also tended to have a positive impact on species richness. Percent cover of woody vegetation showed a positive effect on all three bird diversity indices, i.e., species richness, Shannon-Wiener diversity, and evenness. Percent cover of rice affected species richness positively and evenness negatively, whereas the effects of percent cover of corn were the opposite. In a fourth-corner analysis, the abundance of plant/seed-eating birds was negatively associated with alpha crop diversity, whereas the abundance of ground-foraging birds was positively associated with beta crop diversity. These patterns indicate that seasonally dynamic crop changes as well as local crop diversity can influence bird diversity and traits in small farmlands. They also suggest that natural/semi-natural woody vegetation, such as trees and shrubs, play a critical role in enhancing species diversity of birds in farmlands dominated by herbaceous edible crops.

Abstract Previous studies suggest that a high body mass index (BMI) may be a risk factor for keratoconus (KC), but the causal relationship remains unclear. This study used Mendelian randomization (MR) to investigate this connection and explore the mediating role of circulating serum metabolites and inflammatory factors in this association. Two-sample MR analysis was conducted to assess the relationship between BMI and KC. The study employed a two-step MR approach to evaluate the mediating roles of 91 inflammatory markers and 249 serum metabolites in the BMI-KC relationship. Inverse variance weighting (IVW) was the primary method, and multiple sensitivity analyses were performed to ensure robustness. IVW analysis revealed a positive causal relationship between BMI and KC (OR IVW = 1.811, 95% CI 1.005–3.262, P = 0.048). Although IL-12β and IL-4 were causally associated with KC, they did not mediate the BMI-KC relationship. Five serum metabolites were identified as potential mediators, with HDL cholesterol and triglyceride ratios showing significance. This study clarified the causal relationship between high BMI and KC, suggesting that high BMI may induce KC through lipid metabolism abnormalities. These findings underscore the importance of managing BMI for KC prevention.

Introduction: Targeted protein degradation represents a promising therapeutic approach, while diabetic cardiomyopathy (DCM) arises as a consequence of aberrant insulin secretion and impaired glucose and lipid metabolism in the heart.. Objectives: Considering that the Toll-like receptor 9 (TLR9) signaling pathway plays a pivotal role in regulating energy metabolism, safeguarding cardiomyocytes, and influencing glucose uptake, the primary objective of this study was to investigate the impact of TLR9 on diabetic cardiomyopathy (DCM) and elucidate its underlying mechanism. Methods: Mouse model of DCM was established using intraperitoneal injection of STZ, and mice were transfected with adeno-associated virus serotype 9-TLR9 (AAV9-TLR9) to assess the role of TLR9 in DCM. To explore the mechanism of TLR9 in regulating DCM disease progression, we conducted interactome analysis and employed multiple molecular approaches. Results: Our study revealed a significant correlation between TLR9 expression and mouse DCM. TLR9 overexpression markedly mitigated cardiac dysfunction, myocardial fibrosis, oxidative stress, and apoptosis in DCM, while inflammation levels remained relatively unaffected. Mechanistically, TLR9 overexpression positively modulated mitochondrial bioenergetics and activated the AMPK-PGC1a signaling pathway. Furthermore, we identified Triad3A as an interacting protein that facilitated TLR9′s proteasomal degradation through K48-linked ubiquitination. Inhibiting Triad3A expression improved cardiac function and pathological changes in DCM by enhancing TLR9 activity. Conclusions: The findings of this study highlight the critical role of TLR9 in maintaining cardiac function and mitigating pathological alterations in diabetic cardiomyopathy. Triad3A-mediated regulation of TLR9 expression and function has significant implications for understanding the pathogenesis of DCM. Targeting TLR9 and its interactions with Triad3A may hold promise for the development of novel therapeutic strategies for diabetic cardiomyopathy. Further research is warranted to fully explore the therapeutic potential of TLR9 modulation in the context of cardiovascular diseases.

Abstract To enhance the reaction kinetics without sacrificing activity in porous materials, one potential solution is to utilize the anisotropic distribution of pores and channels besides enriching active centers at the reactive surfaces. Herein, by designing a unique distribution of oriented pores and single crystalline array structures in the presence of abundant acid sites as demonstrated in the ZSM-5 nanorod arrays grown on monoliths, both enhanced dynamics and improved capacity are exhibited simultaneously in propene capture at low temperature within a short duration. Meanwhile, the ZSM-5 array also helps mitigate the long-chain HCs and coking formation due to the enhanced diffusion of reactants in and reaction products out of the array structures. Further integrating the ZSM-5 array with Co3O4 nanoarray enables comprehensive propene removal throughout a wider temperature range. The array structured film design could offer energy-efficient solutions to overcome both sorption and reaction kinetic restrictions in various solid porous materials for various energy and chemical transformation applications.

Abstract Background The effect of nonalcoholic fatty liver disease (NAFLD) on major adverse cardiovascular events (MACEs) can be influenced by the degree of coronary artery stenosis. However, the association between the severity of NAFLD and MACEs in patients who underwent coronary computed tomography angiography (CCTA) is unclear. Methods A total of 341 NAFLD patients who underwent CCTA were enrolled. The severity of NAFLD was divided into mild NAFLD and moderate-severe NAFLD by abdominal CT results. The degree of coronary artery stenosis was evaluated by using Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Cox regression analysis and Kaplan–Meier analysis were used to assess poor prognosis. Results During the follow-up period, 45 of 341 NAFLD patients (13.20%) who underwent CCTA occurred MACEs. The severity of NAFLD (hazard ratio [HR] = 2.95[1.54–5.66]; p = 0.001) and CAD-RADS categories 3–5 (HR = 16.31[6.34–41.92]; p

Highlights Electrodeposited amorphous IrO x thin electrodes are first developed for proton exchange membrane electrolyzer cells. An ultralow loading of 0.075 mg cm−2 archives superior performance to catalyst-coated membrane (2 mg cm−2). > 96% of catalyst savings and > 42-fold higher catalyst utilization are demonstrated.

The endoplasmic reticulum (ER) is one of the largest organelles, and Endoplasmic Reticulum Stress Response Pathway is a series of responses triggered by the homeostatic imbalance of the ER and the state in which unfolded or misfolded proteins accumulate in the ER, which can trigger cell death. Cell death plays a crucial role in the development of diseases such as gynecological oncology. Herein, we review the current research on the response and ovarian cancer, discussing the key sensors (IRE1, PERK, ATF6), and the conditions under which it occurs (Ca2+ homeostasis disruption, hypoxia, others). Using the response as a starting point, provide a comprehensive overview of the relationship with the four types of cell death (apoptosis, autophagy, immunogenic cell death, paraptosis) in an attempt to provide new targeted therapeutic strategies for the organelle-Endoplasmic Reticulum Stress Response Pathway-cell death in ovarian cancer therapy.

BackgroundThe newest clinical evidence that the relationship between the peritoneal cancer index (PCI) and the postoperative prognosis of advanced ovarian cancer patients remains controversial, and there are no large-sample and multicenter studies to clarify this matter. Therefore, in this paper, we used meta-analysis to systematically assess the postoperative prognostic value of PCI in subjects with advanced ovarian cancer to provide individualized treatment plans and thus improve the prognosis of patients.MethodsLiterature on the correlation between PCI and the postoperative prognosis in subjects with advanced OC undergoing cytoreductive surgery (CRS) was searched in the Cochrane Library, Pubmed, Embase, and Web of Science from the database inception to April 20, 2023. The search was updated on February 28, 2024. We only included late-stage (FIGO stage: III-IV) patients who did not undergo neoadjuvant chemotherapy (NACT) or hyperthermic intraperitoneal chemotherapy (HIPEC). Afterwards, literature screening and data extraction were conducted using Endnote20 software. The literature quality was assessed using the Newcastle-Ottawa Scale (NOS). Lastly, statistical analysis was performed with STATA 15.0 software.ResultsFive studies with 774 patients were included. The result indicated that patients with high PCI had a worse prognosis than those with low PCI. The combined hazard ratio was 2.79 [95%CI: (2.04, 3.82), p

BackgroundDespite reports suggesting a link between obesity and keratoconus, the causal relationship is not fully understood.MethodsWe used genome-wide association study (GWAS) data from public databases for a two-sample Mendelian randomization analysis to investigate the causal link between body mass index (BMI) and keratoconus. The primary method was inverse variance weighted (IVW), complemented by different analytical techniques and sensitivity analyses to ensure result robustness. A meta-analysis was also performed to bolster the findings’ reliability.ResultsOur study identified a significant causal relationship between BMI and keratoconus. Out of 20 Mendelian randomization (MR) analyses conducted, 9 showed heterogeneity or pleiotropy. Among the 11 analyses that met all three MR assumptions, 4 demonstrated a significant causal difference between BMI and keratoconus, while the remaining 7 showed a positive trend but were not statistically significant. Meta-analysis confirmed a significant causal relationship between BMI and keratoconus.ConclusionThere is a significant causal relationship between BMI and keratoconus, suggesting that obesity may be a risk factor for keratoconus.

Background Long noncoding RNA (lncRNA) and mRNA profiles in leukocytes have shown potential as biomarkers for acute ischemic stroke (AIS). This study aimed to identify altered lncRNA and target mRNA profiles in peripheral blood leukocytes as biomarkers and to assess the diagnostic value and association with AIS prognosis. Methods and Results Differentially expressed lncRNAs (DElncRNAs) and differentially expressed target mRNAs (DEmRNAs) were screened by RNA sequencing in the discovery set, which consisted of 10 patients with AIS and 20 controls. Validation sets consisted of a multicenter (311 AIS versus 303 controls) and a nested case–control study (351 AIS versus 352 controls). The discriminative value of DElncRNAs and DEmRNAs added to the traditional risk factors was estimated with the area under the curve. NAMPT‐AS, FARP1‐AS1, FTH1, and NAMPT were identified in the multicenter case–control study (P

Abstract Background In December 2022, Chongqing experienced a significant surge in coronavirus disease 2019 (COVID-19) epidemic after adjusting control measures in China. Given the widespread immunization of the population with the BA.5 variant, it is crucial to actively monitor severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant evolution in Chongqing's Yubei district. Methods In this retrospective study based on whole genome sequencing, we collected oropharyngeal and nasal swab of native COVID-19 cases from Yubei district between January to May 2023, along with imported cases from January 2022 to January 2023. Through second-generation sequencing, we generated a total of 578 genomes. Results Phylogenetic analyses revealed these genomes belong to 47 SARS-CoV-2 Pango lineages. BA.5.2.48 was dominant from January to April 2023, rapidly replaced by XBB* variants from April to May 2023. Bayesian Skyline Plot reconstructions indicated a higher evolutionary rate (6.973 × 10–4 subs/site/year) for the XBB.1.5* lineage compared to others. The mean time to the most recent common ancestor (tMRCA) of BA.5.2.48* closely matched BA.2.75* (May 27, 2022). Using multinomial logistic regression, we estimated growth advantages, with XBB.1.9.1 showing the highest growth advantage (1.2, 95% HPI:1.1–1.2), followed by lineage FR.1 (1.1, 95% HPI:1.1–1.2). Conclusions Our monitoring reveals the rapid replacement of the previously prevalent BA.5.2.48 variant by XBB and its sub-variants, underscoring the ineffectiveness of herd immunity and breakthrough BA.5 infections against XBB variants. Given the ongoing evolutionary pressure, sustaining a SARS-CoV-2 genomic surveillance program is imperative.

Abstract Background The mechanisms and risk factors underlying ovarian cancer (OC) remain under investigation, making the identification of new prognostic biomarkers and improved predictive factors critically important. Recently, circulating metabolites have shown potential in predicting survival outcomes and may be associated with the pathogenesis of OC. However, research into their genetic determinants is limited, and there are some inadequacies in understanding the distinct subtypes of OC. In this context, we conducted a Mendelian randomization study aiming to provide evidence for the relationship between genetically determined metabolites (GDMs) and the risk of OC and its subtypes. Methods In this study, we consolidated genetic statistical data of GDMs with OC and its subtypes through a genome-wide association study (GWAS) and conducted a two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method served as the primary approach, with MR-Egger and weighted median methods employed for cross-validation to determine whether a causal relationship exists between the metabolites and OC risk. Moreover, a range of sensitivity analyses were conducted to validate the robustness of the results. MR-Egger intercept, and Cochran’s Q statistical analysis were used to evaluate possible heterogeneity and pleiotropy. False discovery rate (FDR) correction was applied to validate the findings. We also conducted a reverse MR analysis to validate whether the observed blood metabolite levels were influenced by OC risk. Additionally, metabolic pathway analysis was carried out using the MetaboAnalyst 5.0 software. Results In MR analysis, we discovered 18 suggestive causal associations involving 14 known metabolites, 8 metabolites as potential risk factors, and 6 as potential cancer risk reducers. In addition, three significant pathways, "caffeine metabolism," "arginine biosynthesis," and "citrate cycle (TCA cycle)" were associated with the development of mucinous ovarian cancer (MOC). The pathways "caffeine metabolism" and "alpha-linolenic acid metabolism" were associated with the onset of endometrioid ovarian cancer (OCED). Conclusions Our MR analysis revealed both protective and risk-associated metabolites, providing insights into the potential causal relationships between GDMs and the metabolic pathways related to OC and its subtypes. The metabolites that drive OC could be potential candidates for biomarkers.

BackgroundOvarian endometriotic cysts (OEC) represent the primary manifestation of endometriosis, constituting a hormonally dependent inflammatory disorder in gynecology. It significantly affects the quality of life and reproductive health of women. It is worth noting that traditional Chinese medicine (TCM), especially Chinese herbal medicine (CHM), has been widely applied in mainland China due to its unique therapeutic system and commendable clinical efficacy, bringing new hope for preventing and managing OEC.ObjectiveThis study aims to evaluate the efficacy and safety of CHM in the management of postoperative OEC. Simultaneously, it seeks to explore the medication laws, therapeutic principles, and specific treatment mechanisms of CHM.MethodsEight electronic databases were searched from their inception to 01 November 2023. Randomized controlled trials (RCTs) assessing the therapeutic effects and safety of CHM for postoperative OEC were included. The risk of bias for each trial was assessed using the Cochrane Collaboration’s tool. The certainty of the evidence was evaluated using the GRADE profiler 3.2. Additionally, we extracted formulation from the included studies, conducting a thorough analysis.Results(ⅰ) Twenty-two RCTs involving 1938 patients were included. In terms of the primary efficacy outcome, the CHM group demonstrated a potentially lower recurrence rate compared to both control (odds ratio (OR) = 0.25; 95% confidence intervals (CI): 0.10–0.64) and conventional western medicine (CWM) (OR = 0.26; 95% CI: 0.11–0.65) groups. Furthermore, the joint application of CHM and CWM resulted in a significant reduction in the recurrence rate (OR = 0.26; 95% CI: 0.17–0.40). (ⅱ) Regarding secondary efficacy outcomes, (a) Total clinical efficacy rate: CHM showcased an augmentation in clinical effectiveness compared to both the control (OR = 4.23; 95% CI: 1.12–15.99) and CWM (OR = 2.94; 95% CI: 1.34–6.43) groups. The combined administration of CHM and CWM substantially enhanced overall clinical effectiveness (OR = 3.44; 95% CI: 2.37–5.00). (b) VAS Score: CHM exhibited the capacity to diminish the VAS score in comparison to surgery alone (Mean difference (MD) = −0.86; 95% CI: -1.01 to −0.71). Nevertheless, no substantial advantage was observed compared to CWM alone (MD = −0.16; 95% CI: -0.49 to 0.17). The integration of CHM with CWM effectively ameliorated pain symptoms (MD = −0.87; 95% CI: -1.10 to −0.65). (c) Serum Level of Cancer antigen 125 (CA125): the CHM group potentially exhibited lower CA125 levels in comparison to CWM alone (MD = −11.08; 95% CI: -21.75 to −0.42). The combined intervention of CHM and CWM significantly decreased CA125 levels (MD = −5.31; 95% CI: -7.27 to −3.36). (d) Pregnancy Rate: CHM exhibited superiority in enhancing the pregnancy rate compared to surgery (OR = 3.95; 95% CI: 1.60–9.74) or CWM alone (OR = 3.31; 95% CI: 1.40–7.83). The combined utilization of CHM and CWM demonstrated the potential to enhance pregnancy rates compared to CWM (OR = 2.99; 95% CI: 1.28–6.98). Concerning safety outcome indicators, CHM effectively decreased the overall incidence of adverse events and, to a certain extent, alleviated perimenopausal symptoms as well as liver function impairment. (ⅲ) Most of CHMs were originated from classical Chinese herbal formulas. Prunus persica (L.) Batsch (Taoren), Angelica sinensis (Oliv.) Diels (Danggui), Salvia miltiorrhiza Bunge (Danshen), Paeonia lactiflora Pall. (Chishao), and Corydalis yanhusuo W.T.Wang (Yanhusuo) were most frequently used CHM.ConclusionCHM may be a viable choice in the long-term management of postoperative OEC, with the potential to enhance clinical efficacy while decreasing recurrence and adverse effects.

Abstract Understory bird communities, especially those comprising insectivores, are highly sensitive to forest loss and fragmentation. Currently, there is little knowledge regarding the large‐scale diversity patterns of understory bird communities, particularly in Eastern Asia. Consequently, we aimed to identify the distribution patterns of understory birds in southern China and the factors underlying these patterns. We analysed the diversity distribution patterns of taxonomic and functional α and β diversity for understory Passeriformes birds in southern China utilising cluster and ordination analyses. Subsequently, we analysed the effects of geographic distance, annual mean temperature, annual temperature range, annual mean precipitation, and annual precipitation range on diversity distribution patterns. In total, 9282 individuals belonging to 11 orders, 48 families, and 297 species were captured over 98,544 net hours, with Alcippeidae being the most abundant family in southern China. The understory bird communities of the 25 sites were categorised into six sub‐regions of the Oriental Realm (Indo‐Malayan Realm). The pattern in the distribution of taxonomic and functional β‐diversity of understory birds in southern China was consistent with zoogeographical regionalisation. Three distinct geographical groups were identified: Group 1 was located in the Min‐Guang Coast and Hainan sub‐regions; Group 2 was located in the East Hilly Plain, Southwest Mountains, and Western Mountains and Plateaus sub‐regions; and Group 3 was located in the Southern Yunnan Mountain subregion. The most critical factors related to the distribution patterns of β‐diversity were geographical distance, annual mean temperature, and annual temperature range. Our results showed that the understory bird communities of the Southwest Mountain, East Hilly Plain, and Western Mountains, and Plateaus sub‐regions were similar, as were those of the Min‐Guang Coast and Hainan sub‐regions. Our results underscore the joint roles of distance, temperature, and historical evolution in understory bird communities.

Abstract Background Dyslipidemia and inflammation are significant factors for the onset of cardiovascular diseases (CVD); however, studies regarding their interactions on the risk of CVD are scarce. This study aimed to assess the interaction of dyslipidemia and high-sensitivity C-reactive protein (hs-CRP) on CVD. Methods This prospective cohort enrolled 4,128 adults at baseline in 2009 and followed them up until May 2022 for collecting CVD events. Cox-proportional hazard regression analysis estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) of the associations of increased hs-CRP (≥ 1 mg/L) and dyslipidemia with CVD. The additive interactions were explored using the relative excess risk of interaction (RERI) and the multiplicative interactions were assessed with HRs (95% CI) while the multiplicative interactions were assessed by the HRs (95% CI) of interaction terms. Results The HRs of the association between increased hs-CRP and CVD were 1.42 (95% CI: 1.14–1.79) and 1.17 (95% CI: 0.89–1.53) among subjects with normal lipid levels and subjects with dyslipidemia, respectively. Stratified analyses by hs-CRP levels showed that among participants with normal hs-CRP ( 2.10 g/L had a significant association with CVD [HR (95% CI): 1.69 (1.14–2.51)]. Interaction analyses showed that increased hs-CRP had multiplicative and additive interactions with LDL-C ≥ 160 mg/dL and non-HDL-C ≥ 190 mg/dL on the risk of CVD [HRs (95%CIs): 0.309 (0.153–0.621), and 0.505 (0.295–0.866); RERIs (95%CIs): -1.704 (-3.430-0.021 and − 0.694 (-1.476-0.089), respectively, all P

Multimodal emotion recognition techniques are increasingly essential for assessing mental states. Image-based methods, however, tend to focus predominantly on overt visual cues and often overlook subtler mental state changes. Psychophysiological research has demonstrated that heart rate (HR) and skin temperature are effective in detecting autonomic nervous system (ANS) activities, thereby revealing these subtle changes. However, traditional HR tools are generally more costly and less portable, while skin temperature analysis usually necessitates extensive manual processing. Advances in remote photoplethysmography (r-PPG) and automatic thermal region of interest (ROI) detection algorithms have been developed to address these issues, yet their accuracy in practical applications remains limited. This study aims to bridge this gap by integrating r-PPG with thermal imaging to enhance prediction performance. Ninety participants completed a 20-min questionnaire to induce cognitive stress, followed by watching a film aimed at eliciting moral elevation. The results demonstrate that the combination of r-PPG and thermal imaging effectively detects emotional shifts. Using r-PPG alone, the prediction accuracy was 77% for cognitive stress and 61% for moral elevation, as determined by a support vector machine (SVM). Thermal imaging alone achieved 79% accuracy for cognitive stress and 78% for moral elevation, utilizing a random forest (RF) algorithm. An early fusion strategy of these modalities significantly improved accuracies, achieving 87% for cognitive stress and 83% for moral elevation using RF. Further analysis, which utilized statistical metrics and explainable machine learning methods including SHapley Additive exPlanations (SHAP), highlighted key features and clarified the relationship between cardiac responses and facial temperature variations. Notably, it was observed that cardiovascular features derived from r-PPG models had a more pronounced influence in data fusion, despite thermal imaging’s higher predictive accuracy in unimodal analysis.

Continuous development of remote sensing technology can rapidly and accurately extract secondary disaster information, such as the area of various disasters. However, in the extraction process, some disasters should be initially classified and identified. In view of this concept, a lightweight fully Convolutional Neural Network (CNN) model Earthquake – Flood–Fire – Cyclone (EFFC)-Net is proposed. Two modules, EFFC_Block and EFFC_Tran_Block, which are used for feature extraction and feature transformation, respectively, are introduced. The EFFC-Net network model is reconstructed through the EFFC_Block and EFFC_Tran_Block modules. Subsequently, EFFC-Net is compared with CNN and transformer models. Results show that the EFFC-Net network model performs effectively in precision, recall, F1_score, and parameters, outperforming the more advanced CNN and transformer models. Moreover, the test time of the Cifar_10 and Cifar_100 datasets was compared, and the results indicate that the EFFC-Net algorithm has the shortest running time and achieves the lightweight goal. Therefore, the EFFC-Net lightweight fully CNN has high disaster classification application value and good portability.

Abstract Background Differentiating between solitary spinal metastasis (SSM) and solitary primary spinal tumor (SPST) is essential for treatment decisions and prognosis. The aim of this study was to develop and validate an MRI-based radiomics nomogram for discriminating SSM from SPST. Methods One hundred and thirty-five patients with solitary spinal tumors were retrospectively studied and the data set was divided into two groups: a training set (n = 98) and a validation set (n = 37). Demographics and MRI characteristic features were evaluated to build a clinical factors model. Radiomics features were extracted from sagittal T1-weighted and fat-saturated T2-weighted images, and a radiomics signature model was constructed. A radiomics nomogram was established by combining radiomics features and significant clinical factors. The diagnostic performance of the three models was evaluated using receiver operator characteristic (ROC) curves on the training and validation sets. The Hosmer–Lemeshow test was performed to assess the calibration capability of radiomics nomogram, and we used decision curve analysis (DCA) to estimate the clinical usefulness. Results The age, signal, and boundaries were used to construct the clinical factors model. Twenty-six features from MR images were used to build the radiomics signature. The radiomics nomogram achieved good performance for differentiating SSM from SPST with an area under the curve (AUC) of 0.980 in the training set and an AUC of 0.924 in the validation set. The Hosmer–Lemeshow test and decision curve analysis demonstrated the radiomics nomogram outperformed the clinical factors model. Conclusions A radiomics nomogram as a noninvasive diagnostic method, which combines radiomics features and clinical factors, is helpful in distinguishing between SSM and SPST.

The Snf2 protein family is a group of ATP-dependent chromatin remodeling factors (CHRs) that play an essential role in gene expression regulation. In plants, Snf2 is involved in growth, development, as well as stress resistance. However, only a very limited number of experimentally validated Snf2 have been identified and reported, while the majority remaining undiscovered in most species . In this study, we predicted 3135 Snf2 proteins and 8398 chromatin remodeling complex (CRC) subunits in diverse plant species, and constructed the Plant Chromatin Remodeling Factors Database (PlantCHRs, http://www.functionalgenomics.cn/PlantCHRs/), which provide a comprehensive resource for researchers to access information about plant CHRs. We also developed an online tool capable of predicting CHRs and CRC subunits. Moreover, we investigated the distribution of Snf2 proteins in different species and observed a significant increase in the number of Snf2 proteins and the diversity of the Snf2 subfamily during the evolution, highlighting their evolutionary importance. By analyzing the expression patterns of the Snf2 genes in different tissues of maize and Arabidopsis, we found that the Snf2 proteins may show some conservation across different species in regulating plant growth and development. Over the all, we established a comprehensive database for plant CHRs, which will facilitate the researches on plant chromatin remodeling.

BackgroundGene therapy involves introducing and editing foreign genes in the body to treat and prevent genetic diseases. Adeno-associated virus (AAV) vector has become a widely used tool in gene therapy due to its high safety and transfection efficiency.MethodsThis study employs bibliometric analysis to explore the foundation and current state of AAV vector application in gene therapy research. A total of 6,069 publications from 1991 to 2022 were analyzed, retrieved from the Science Citation Index Expanded (SCI-E) within the Web of Science Core Collection (WoSCC) of Clarivate Analytics. Institutions, authors, journals, references, and keywords were analyzed and visualized by using VOSviewer and CiteSpace. The R language and Microsoft Excel 365 were used for statistical analyses.ResultsThe global literature on AAV vector and gene therapy exhibited consistent growth, with the United States leading in productivity, contributing 3,868 papers and obtaining the highest H-index. Noteworthy authors like Wilson JM, Samulski RJ, Hauswirth WW, and Mingozzi F were among the top 10 most productive and co-cited authors. The journal “Human Gene Therapy” published the most papers (n = 485) on AAV vector and gene therapy. Current research focuses on “gene editing,” “gene structure,” “CRISPR,” and “AAV gene therapy for specific hereditary diseases.”ConclusionThe application of AAV vector in gene therapy has shown continuous growth, fostering international cooperation among countries and institutions. The intersection of gene editing, gene structure, CRISPR, and AAV gene therapy for specific hereditary diseases and AAV vector represents a prominent and prioritized focus in contemporary gene therapy research. This study provides valuable insights into the trends and characteristics of AAV gene therapy research, facilitating further advancements in the field.

With the development of science and technology and the improvement of the quality of life, ophthalmic diseases have become one of the major disorders that affect the quality of life of people. In view of this, we propose a new method of ophthalmic disease classification, ED-Net (Eye Disease Classification Net), which is composed of the ED_Resnet model and ED_Xception model, and we compare our ED-Net method with classical classification algorithms, transformer algorithm, more advanced image classification algorithms and ophthalmic disease classification algorithms. We propose the ED_Resnet module and ED_Xception module and reconstruct these two modules into a new image classification algorithm ED-Net, and compared them with classical classification algorithms, transformer algorithms, more advanced image classification algorithms and eye disease classification algorithms.

In the event of a sudden natural disaster, the damaged communication infrastructure cannot provide a necessary network service for vehicles. Unfortunately, this is the critical moment when the occupants of trapped vehicles need to urgently use the vehicular network’s emergency service. How to efficiently connect the trapped vehicle to the base station is the challenge facing the emergency vehicular network. To address this challenge, this study proposes a UAV-assisted multi-objective and multi-hop ad hoc network (UMMVN) that can be used as an emergency vehicular network. Firstly, it presents an integrated design of a search system to find a trapped vehicle, the communication relay, and the networking, which significantly decreases the UAV’s networking time cost. Secondly, it presents a multi-objective search for a trapped vehicle and navigates UAVs along multiple paths to different objectives. Thirdly, it presents an optimal branching node strategy that allows the adequate use of the overlapping paths to multiple targets, which decreases the networking cost within the limited communication and searching range. The numerical experiments illustrate that the UMMVN performs better than other state-of-the-art networking methods.

The emergence and development of induced pluripotent stem cells (iPSCs) provides an approach to understand the regulatory mechanisms of cell pluripotency and demonstrates the great potential of iPSCs in disease modeling. Acute myelitis defines a group of inflammatory diseases that cause acute nerve damage in the spinal cord; however, its pathophysiology remains to be elusive. In this study, we derived skin fibroblasts from a patient with acute myelitis (P-HAF) and then reprogrammed P-HAF cells to iPSCs using eight exogenous factors (namely, OCT4, SOX2, c-MYC, KLF4, NANOG, LIN28, RARG, and LRH1). We performed transcriptomic analysis of the P-HAF and compared the biological characteristics of the iPSCs derived from the patient (P-iPSCs) with those derived from normal individuals in terms of pluripotency, transcriptomic characteristics, and differentiation ability toward the ectoderm. Compared to the control iPSCs, the P-iPSCs displayed similar features of pluripotency and comparable capability of ectoderm differentiation in the specified culture. However, when tested in the common medium, the P-iPSCs showed attenuated potential for ectoderm differentiation. The transcriptomic analysis revealed that pathways enriched in P-iPSCs included those involved in Wnt signaling. To this end, we treated iPSCs and P-iPSCs with the Wnt signaling pathway inhibitor IWR1 during the differentiation process and found that the expression of the ectoderm marker Sox1 was increased significantly in P-iPSCs. This study provides a novel approach to investigating the pathogenesis of acute myelitis.

Abstract. Background:. MicroRNA-20a (miR-20a) is dysregulated in many types of malignancies, including human hepatocellular carcinoma (HCC), but its expression level and functional significance in HCC are still disputed. We aimed to study the role of miR-20a-5p in HCC and its downstream molecular mechanisms. Methods:. We used real-time polymerase chain reaction to detect the expression of miR-20a-5p and runt-related transcription factor 3 (RUNX3) in HCC and paraneoplastic tissue, transfected Huh7 and highly metastatic human hepatocellular carcinoma (MHCC97H) cells. A live cell workstation was used to observe the proliferation and migration of transfected cells. The invasiveness of transfected cells was verified by Transwell assay. Cell apoptosis was detected by flow cytometry. The expression levels of proteins after transfection were measured using simple western immunoblot measurements. Gene expression profiles between HCC and normal samples were obtained from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were processed by the database for annotation, visualization and integrated discovery. Potential target genes of miR-20a-5p were predicted to further investigate how miR-20a-5p regulates epithelial-mesenchymal transition (EMT) in HCC. Results:. MiR-20a-5p was significantly highly expressed in HCC tissues, and overexpression of miR-20a-5p significantly promoted HCC cell proliferation, migration, and invasion and inhibited apoptosis in vitro. The protein expression of E-cadherin was decreased and that of vimentin was increased after overexpression of miR-20a-5p in HCC cells. We discovered the intersection of genes from miRDB, miR TarBase, and TargetScan, obtained 397 target genes and finally focused on RUNX3. RUNX3 was not only reduced in HCC specimens but also drastically reduced in HCC cells overexpressing miR-20a-5p. RUNX3 expression decreased with elevated miR-20a-5p, which activated downstream EMT signaling and promoted cell proliferation, migration, and invasion. Conclusions:. Since RUNX3 is involved in EMT in HCC, as proven by previous research, our findings provide further evidence for a novel regulatory pathway comprising the miR-20a/RUNX3/EMT axis that upregulates EMT signaling and enhances the migration of HCC cells.

Abstract Background Spodoptera litura is an important polyphagous pest that causes significant damage to the agricultural sector. We performed RNA-seq of 15 S. litura individuals from larval (fifth and sixth instar larvae), chrysalis, and adult developmental stages. We also compared the S. litura transcriptome data with Spodoptera frugiperda across the same developmental stages, which was sequenced in our previous study. Results A total of 101,885 differentially expressed transcripts (DETs) were identified in S. litura. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that S. litura may undergo active xenobiotic and detoxifying metabolism during its larval and adult stages, which may explain difficulties with current population control measures. We also found that DETs of single-copy orthologous genes between S. litura and S. frugiperda were involved in basic metabolism and development. However, energy and metabolic processes genes had a higher expression in S. litura, whereas nervous and olfactory function genes had a higher expression in S. frugiperda. Metagenomics analysis in larval S. litura and S. frugiperda revealed that microbiota participate in the detoxification and metabolism processes, but the relative abundance of detoxification-related microbiota was more abundant in S. frugiperda. Transcriptome results also confirmed the detoxification-related pathway of S. frugiperda was more abundant than in S. litura. Conclusions Significant changes at transcriptional level were identified during the different development stages of S. litura. Importantly, we also identified detoxification associated genes and gut microbiota between S. litura and S. frugiperda at different developmental stages, which will be valuable in revealing possible mechanisms of detoxification and development in these two lepidopterans.

ABSTRACT We conducted UPLC-MS-based metabolomics, 16S rRNA, and metagenome sequencing on the fecal samples of 44 captive giant pandas (Ailuropoda melanoleuca) from four age groups (i.e., Cub, Young, Adult, and Old) to comprehensively understand age-related changes in the metabolism and gut microbiota of giant pandas. We characterized the metabolite profiles of giant pandas based on 1,376 identified metabolites, with 152 significantly differential metabolites (SDMs) found across the age groups. We found that the metabolites and the composition/function of the gut microbiota changed in response to the transition from a milk-dominant diet in panda cubs to a bamboo-specific diet in young and adult pandas. Lipid metabolites such as choline and hippuric acid were enriched in the Cub group, and many plant secondary metabolites were significantly higher in the Young and Adult groups, while oxidative stress and inflammatory related metabolites were only found in the Old group. However, there was a decrease in the α-diversity of gut microbiota in adult and old pandas, who exclusively consume bamboo. The abundance of bacteria related to the digestion of cellulose-rich food, such as Firmicutes, Streptococcus, and Clostridium, significantly increased from the Cub to the Adult group, while the abundance of beneficial bacteria such as Faecalibacterium, Sarcina, and Blautia significantly decreased. Notably, several potential pathogenic bacteria had relatively high abundances, especially in the Young group. Metagenomic analysis identified 277 CAZyme genes including cellulose degrading genes, and seven of the CAZymes had abundances that significantly differed between age groups. We also identified 237 antibiotic resistance genes (ARGs) whose number and diversity increased with age. We also found a significant positive correlation between the abundance of bile acids and gut bacteria, especially Lactobacillus and Bifidobacterium. Our results from metabolome, 16S rRNA, and metagenome data highlight the important role of the gut microbiota-bile acid axis in the regulation of age-related metabolism and provide new insights into the lipid metabolism of giant pandas. IMPORTANCE The giant panda is a member of the order Carnivora but is entirely herbivorous. The giant panda’s specialized diet and related metabolic mechanisms have not been fully understood. It is therefore crucial to investigate the dynamic changes in metabolites as giant pandas grow and physiologically adapt to their herbivorous diet. This study conducted UPLC-MS-based metabolomics 16S rRNA, and metagenome sequencing on the fecal samples of captive giant pandas from four age groups. We found that metabolites and the composition/function of gut microbiota changed in response to the transition from a milk-dominant diet in cubs to a bamboo-specific diet in young and adult pandas. The metabolome, 16S rRNA, and metagenome results highlight that the gut microbiota-bile acid axis has an important role in the regulation of age-related metabolism, and our study provides new insights into the lipid metabolism of giant pandas.

BackgroundThrombospondin Type 1 Domain Containing Protein 1 (THSD1) has been suggested to be a new regulator of endothelial barrier function in the angiogenesis process, preserving vascular integrity. We sought to characterize the association of THSD1 genetic variants and mRNA expression with the risk of hemorrhagic stroke (HS) with population-based evidence.MethodsA case–control study was conducted with 843 HS cases and 1,400 healthy controls. A cohort study enrolled 4,080 participants free of stroke at baseline in 2009 and followed up to 2022. A synonymous variant, the main tag SNP rs3803264 of the THSD1 gene, was genotyped in all subjects, and peripheral leukocyte THSD1 mRNA expression was detected using RT-qPCR in 57 HS cases and 119 controls.ResultsIn the case–control study, rs3803264 AG/GG variations are associated with a decreased risk of HS with odd ratio (OR) and 95% confidence interval (CI) of the dominant model of 0.788 (0.648–0.958), p = 0.017. In addition, rs3803264 and dyslipidemia had a multiplicative interaction [OR (95% CI) = 1.389 (1.032, 1.869), p = 0.030]. In the cohort study, a similar association strength of rs3803264 dominant model and the risk of HS was observed with the incidence rate ratio (IRR) of 0.734 and p-value of 0.383. Furthermore, the risk of HS showed a non-linear as THSD1 mRNA expression increased (p for non-linearity

With the enlargement and intensification of oil storages, the technologies and equipment used in the tank farm are quite complicated. Hence, once any fire accident occurs, the domino effect may be triggered with catastrophic consequences. In order to reduce the impact of oil storage accidents on the surrounding personnel and environment, the model of safety barrier was established with the event tree and Bayesian network method by considering the performance of three types of safety barrier, including the active, passive, emergency and response measures, and the probability of the domino effect was evaluated quantitatively. The results show that: the multi-layer safety barriers can reduce the probability of domino effect by 3 to 7 orders of magnitude and the probability of the multi-level domino effect to a greater extent. Besides, the passive protection barrier is the most effective, followed by the emergency and response measures, and the active barrier is the least effective. Generally, the research results can provide some guidance for reducing the damage and impact of regional accidents in the areas where multiple devices are concentrated.

Stock market volatility research has long been the focus of industry and academia, and stock trend forecasting is challenging. Existing research focuses more on how to aggregate historical price features into graph networks, ignoring the effects of other information such as news and current events on forecasts. Most existing graph-based learning methods create stock graphs by manually constructing stock relationships, ignoring the complexity of stock relationships. Based on these, we propose a novel multilevel graph attention network (ML-GAT) for predicting the stock market trends. To be more specific, we initialize the node representations captured by each feature extraction module, then update the stock nodes in the isomorphic graph converted from Wikidata using ML-GAT, selectively aggregate the information of various relation types, aggregate the information to the node representation, and finally feed the result to a particular forecast layer for forecasting, completing the trend forecast of 423 stocks in the S&P 500 index and 286 stocks in the CSI 300 index. By comparing 5 popular approaches, the experimental research verifies ML-GAT’S state-of-the-art performance in prediction tasks. In comparison with the best performance benchmark model, the F1-score and accuracy increased by 11.82% and 12.6%, respectively, and the average daily return and Sharpe rate rose by 5.06 percent and 94.81 percent, respectively. More significantly, our model’s stock linkages are interpretable and consistent with real-world interactions.

For CO2 transportation, as an intermediate link in the construction of large-scale carbon capture, utilization and storage projects, pipeline transportation is the preferred. Therefore, the economic evaluation model of CO2 pipeline transportation is the basis for evaluating its return on investment and optimizing the parameters of pipeline transportation. By comparing and analyzing the calculation formula of CO2 pipeline diameter, an economic evaluation model was established and thereby, the economic evaluation of pipeline diameter was performed based on a case of supercritical CO2 pipeline engineering. The results show that the unit cost of supercritical CO2 pipeline transportation decreases first and then increases with the increase of the pipeline diameter. For the pipeline with a transport capacity of 1×106 t/a and a length of 200 km, the unit transportation cost of CO2 is the lowest at the pipeline diameter of 240 mm. Since the calculation result of the Vandeginste pipeline diameter formula is close to the theoretical optimal pipeline diameter, the Vandeginste pipeline diameter formula is recommended for the calculation of the pipeline diameter in the actual projects. However, the pipeline cost saved at a nominal diameter of 200 mm is far greater than the increment of energy consumption, and thus the annual cost in this case is the minimum. In addition, the unit transportation cost decreases with the increase of transportation distance, and the unit cost trends to be stable when the distance is longer than 200 km. Therefore, the research results could provide scientific basis and reference for the decision-making concerning the economic pipeline transportation of CO2.

With the large-scaling and intensification of crude oil reserves, storage tanks are also developed in the direction of large capacity. Hence, it is easy to trigger a chain fire effect in the tank farm once a fire occurs, causing huge economic losses and even casualties. In order to reasonably design the safety distance of large crude oil storage tanks and reduce the heat radiation effect of the firing tank on the adjacent tanks, the fire of the storage tank was numerically simulated with the CFD technology. Meanwhile, the influence of the three factors, including the wind speed, spray intensity and oil burning rate, on the safety distance of large crude oil storage tanks were analyzed by controlling a single variable and designing the orthogonal working conditions. The results show that the three factors ranking in a decreasing order of influence are the spray intensity, wind speed and oil burning rate successively. To reduce the safety distance between the storage tanks, it is recommended to increase the spray intensity of cooling water. Thereby, the research results could provide guidance for the layout design of crude oil reserves.

Cancer cells harbor many genetic mutations and gene expression profiles different from normal cells. Patient-derived cancer cells (PDCC) are preferred materials in cancer study. We established patient-derived spheroids (PDSs) and patient-derived organoids (PDOs) from PDCCs isolated from the malignant pleural effusion in 8 patients. The morphologies suggested that PDSs may be a model of local cancer extensions, while PDOs may be a model of distant cancer metastases. The gene expression profiles differed between PDSs and PDOs: Gene sets related to inflammatory responses and EMT were antithetically regulated in PDSs or in PDOs. PDSs demonstrated an attenuation of the pathways that contribute to the enhancement of transforming growth factor beta (TGF-β) induced epithelial mesenchymal transition (EMT), while PDOs demonstrated an attenuation of it. Taken together, PDSs and PDOs have differences in both the interaction to the immune systems and to the stroma. PDSs and PDOs will provide a model system that enable intimate investigation of the behavior of cancer cells in the body.

As we all know, natural disasters have a great impact on people’s lives and properties, and it is very necessary to deal with disaster categories in a timely and effective manner. In light of this, we propose using tandem stitching to create a new Disaster Cassification network D-Net (Disaster Cassification Net) using the D-Conv, D-Linear, D-model, and D-Layer modules. During the experiment, we compared the proposed method with “CNN” and “Transformer”, we found that disaster cassification net compared to CNN algorithm Params decreased by 26–608 times, FLOPs decreased by up to 21 times, Precision increased by 1.6%–43.5%; we found that disaster cassification net compared to Transformer algorithm Params decreased by 23–149 times, FLOPs decreased by 1.7–10 times, Precision increased by 3.9%–25.9%. Precision increased by 3.9%–25.9%. And found that disaster cassification net achieves the effect of SOTA(State-Of-The-Art) on the disaster dataset; After that, we compared the above-mentioned MobileNet_v2 with the best performance on the classification dataset and CCT network are compared with disaster cassification net on fashion_mnist and CIFAR_100 public datasets, respectively, and the results show that disaster cassification net can still achieve the state-of-the-art classification effect. Therefore, our proposed algorithm can be applied not only to disaster tasks, but also to other classification tasks.

Due to the corrosive perforation and third-party damage, multiple leakage accidents occurred to the long-distance oil and gas pipelines, for which on-site emergency repair was required, and further pipeline alignment should be performed before welding. For this reason, a series of pipelines with different steel grades, different pipe diameters and different wall thicknesses were taken as the research object, and in order to meet the requirements of the emergency repair operations of long-distance gas pipelines such as alignment for pipeline displacement, the pipe-soil coupling effect was considered according to the structural characteristics of the long-distance pipelines and the mechanical characteristics of the soil around the pipeline. Besides, deformation simulation and stress analysis were conducted for the buried pipelines with D-P model, and the maximum allowable displacement of the free end of pipelines in different excavation lengths of various series of pipelines was solved. The results show that the maximum allowable displacement of the free end of pipelines is jointly affected by the pipe diameter, wall thickness and steel grade. Definitely, it is positively correlated with the excavation length and the wall thickness, but negatively correlated with the pipe diameter. Generally, the calculation results can provide a theoretical reference for the pipeline excavation length during emergency repair operations.

BackgroundThrombospondin-1 (THBS1) derived from platelets and acted as a critical mediator of hemostasis promoting platelet activation in thrombus formation. The biological connection of genetic variants and mRNA expression of THBS1 with ischemic stroke (IS) warrants further validation with population-based evidence.ObjectiveTo evaluate the association of single nucleotide polymorphisms (SNPs) and mRNA expression of THBS1 with the risks of IS and long-term death after stroke.MethodsA case-control study consisted of 4,584 IS patients recruited from five hospitals in Jiangsu, China, and 4,663 age-gender-matched controls free of IS. A cohort study enrolled 4,098 participants free of stroke and lasted from 2009 to 2022. Early collected 3158 IS patients aged between 35 and 80 years were followed up an average of 5.86-year to follow up their long-term death outcomes. Two tagSNPs of the THBS1 gene, rs2236471 and rs3743125, were genotyped in all subjects and THBS1 mRNA expression of peripheral leukocyte was measured using RT-qPCR in 314 IS cases and 314 controls.ResultsThere is no significant difference in genotype and haplotype frequencies of rs2236741 and rs3743125 between IS cases and controls (all P > 0.05). Furthermore, the cohort studies did not observe significant associations between THBS1 variants and the risk of IS incidence or long-term death after IS (all P > 0.05). The THBS1 mRNA expression level (2–ΔΔCT) in IS cases was approximately equal to that in controls (1.01 vs. 0.99, P = 0.833). In addition, THBS1 mRNA expression had no significant association with all-cause death, stroke death, and IS death of IS patients (all P > 0.05).ConclusionTherefore, our study suggested that there is no significant association of THBS1 polymorphisms and mRNA expression level with the risk of IS and long-term death after IS.

Background & aims Liver resection (LR) and radiofrequency ablation (RFA) are commonly used for the treatment of recurrent hepatocellular carcinoma (HCC), but the optimal treatment modality remains unclear. We aimed to compare the efficacy and safety of LR vs RFA for recurrent HCC. Methods We searched PubMed, Embase, Web of Science, and the Cochrane Library for relevant studies. The primary outcomes were overall survival (OS) and disease-free survival (DFS). The secondary outcomes were major complications and hospital stay. Results Eighteen studies with 1991 patients with recurrent HCC were included. The pooled hazard ratio (HR) for OS demonstrated that LR had significantly better OS than RFA in recurrent HCC (HR, 0.81; 95% confidence interval [CI], 0.68–0.95). Specifically, LR was associated with higher 2-, 3- and 4-year OS rates compared with RFA. The pooled HR for DFS showed no significant difference between LR and RFA during the whole follow-up period (HR, 0.90; 95% CI, 0.76–1.07). However, LR was associated with significantly higher 2- to 5-year DFS rates compared to RFA. LR was also associated with more major complications (p

Abstract Background Peripheral immune response has been revealed to play a critical role in proliferative vitreoretinopathy (PVR). However, the reliable immune-related factors that are acting as prognostic indicators or therapeutic targets for PVR remain to explore further. Methods In the current study, we applied whole-transcriptome sequencing to profile peripheral blood mononuclear cells from PVR patients and also analyzed lncRNA-mRNA interactions in peripheral immune cells to explore the pathways that might mediate immunopathology and resultant retinal damage in PVR. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and Ingenuity Pathway Analysis (IPA) were employed to classify the function of these differentially expressed genes. Results Compared to the controls, there were 319 genes upregulated, and 191 genes downregulated in PVR patients. GO, and KEGG enrichment analyses as well as IPA showed that these upregulated genes were significantly enriched in immune-related and infection-relate terms. Immune-related gene NFKBIA, CXCL2, and CXCL8 were detected as hub-genes in the co-expression network, while lncRNAs such as AC007032.1, AC037198.2, AL929472.2, and SLED1 were highly co-expressed with them. lncRNA-mRNA interactions analysis also showed that putative targeted genes of these differentially expressed lncRNAs were also significantly enriched in immune-related or infection-relate pathways. Conclusion Our study highlights the transformation of immune-related genes/pathways in PVR by comparing controls, and validates several critical genes and lncRNAs, which are serving as potential diagnostic markers for PVR patients.

In this work, a typical tunnel 150 m in length is selected and modelled at a scale of 1:15 to assess its effects on smoke control. A total of 32 model tests on smoke flow pattern and longitudinal temperature distribution have been carried out based on the Froude similarity criterion. The results show that smoke control is affected by three factors, namely, the longitudinal airflow velocity, number of opened smoke-exhaust dampers, and fire power, out of which the longitudinal airflow velocity has the greatest effect on smoke control.

Abnormal events involving hidden dangers, near misses and non-casualty accidents are the early warning and signs of serious accidents.Considering the high frequency of such incidents, the accident model was established to identify and correct unsafe factors in such incidents so as to effectively prevent serious accidents.According to the process features and accident characteristics of the tank area, the System Hazard Identification, Prediction and Prevention(SHIPP) model was improved, and the tank area accident model based on safety barriers was built.The cause-consequence relationship model was constructed by combining fault tree and event tree, which were mapped into Bayesian network to characterize uncertainty and conditional dependence.As for new evidence information, probability updating was implemented through Bayesian network update mechanism.Though the empirically learning on the field abnormal event data based on Bayesian theory, the uncertainty of prior probability can be reduced and the dynamic risk prediction of accidents in oil tank area can be implemented.A tank area case was analyzed and the results show that, the probability of material and energy release in the tank area is high, the overall safety performance tends to deteriorate, and the safety inspection and hidden danger investigation should be strengthened.The research results can provide scientific guidance and decision support for risk prediction and accident prevention of large oil tank area.

BackgroundData on the relative risk of malignant transformation in ulcerative colitis (UC) are insufficient. We investigated the potential value of the Mayo endoscopic score (MES) for predicting malignant transformation in patients with UC.MethodsData of patients with UC evaluated at our institute from June 1986 to December 2019 were retrospectively analyzed. The MES used in the study indicated the results of the first colonoscopy after hospitalization. We defined MES of 0–1 as low and MES of 2–3 as high. Univariable and multivariate logistic regression models were used for statistical analysis.ResultsAmong the 280 eligible patients with UC with a median follow-up time of 14 (interquartile range, 10.0–18.0) years, those with a high MES were more likely to develop malignant transformation. High MES positively correlated with the degree of malignancy and was an independent risk factor for UC-associated dysplasia and colorectal cancer (CRC, odds ratio [OR], 9.223; 95% confidence interval [CI], 1.160–73.323; p = 0.036). Disease duration >5 years (OR, 2.05; 95% CI, 1.177–3.572; p = 0.011), immunomodulator use (OR, 4.314; 95% CI, 1.725–10.785; p = 0.002), biologics nonuse (OR, 3.901; 95%CI, 2.213–6.876; p < 0.001), and Hb

Despite an estimated population of 10 million autistic individuals, there is still a significant lack of research on autistic adults in China. This study aimed to investigate the extent and factors influencing community integration (employment, independent living and friendship) and life satisfaction among young autistic adults in China, and compare them with an autistic adult sample with similar characteristics (58%-63% with a reported IQ below 70) from the Netherlands. Data were collected via online surveys to the caregivers of 99 young autistic adults (18-30 years) in China and 109 in the Netherlands, because the autistic adults were not able to fill in the survey independently. Autistic adults in both countries were reported to have limited community integration, as indicated by low rates of employment, limited independent living and few close friendships. Proxy-reported life satisfaction of autistic adults seemed relatively low in both countries, but even lower in Chinese adults, possibly due to limited awareness and acceptance of autism in China, inadequate or inaccessible support services, higher parenting stress, or general cross-country differences in well-being. In general, the findings indicate a common challenge faced by autistic adults with high support needs in both China and the Netherlands.

Background: Leptin has been shown to stimulate the hypothalamus-pituitary-thyroid (HPT) axis in vivo and vitro. Its role in thyroid axis regulation after weight loss induced by bariatric surgery is still unknown. The aim of this study was to evaluate the influence of leptin on weight loss and thyroid function variation induced by Roux-en-Y gastric bypass (RYGB) surgery in euthyroid individuals with obesity and type 2 diabetes mellitus (T2DM). Methods: 65 Chinese individuals with obesity and T2DM who underwent RYGB, and 27 healthy volunteers were enrolled in this retrospective study. Participants were evaluated for changes in anthropometric parameters, metabolic indexes, thyroid function, and leptin levels before and 12 months after surgery. Results: After RYGB, all of these patients experienced significant weight reduction and improved glucose control. Metabolic parameters were significantly ameliorated after surgery compared with baseline. Thyroid hormones including free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) declined in parallel. Median (IQR) plasma leptin levels decreased from 33.7 ng/mL (17.9–63.1) to 10.3 ng/mL (4.0–18.5). Pearson correlation analysis showed that TSH was significantly positively correlated with body mass index, C-reactive protein (CRP), and leptin. Multiple stepwise linear regression indicated that leptin and CRP were independent factors affecting TSH. The β coefficients were 0.38 (p = 0.001) and 0.32 (p = 0.004), respectively. There was a significant positive correlation between ΔTSH and Δleptin (r = 0.33, p = 0.01). Conclusion: Decreased or normalized TSH levels after weight loss induced by RYGB might be mediated by the decline in leptin. There could be cross talk between adipose tissue and the HPT axis.

Background: Intestinal obstruction caused by intestinal fibrosis is a common and serious complication of Crohn's disease (CD). Intestinal fibroblasts, the main effector cells mediating gastrointestinal fibrosis, are activated during chronic inflammation. However, the mechanism of fibroblast activation in CD has not been well elucidated. Methods: Fibroblasts isolated from stenotic and nonstenotic intestines of CD patients were used for RNA sequencing. Immunohistochemical and immunofluorescent staining was performed to evaluate the correlation between intestinal fibrosis and YAP/TAZ expression in our CD cohort and a DSS-induced chronic colitis murine model. A Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) inhibitor was used to explore the ROCK1-YAP/TAZ axis in intestinal fibroblasts in vitro and DSS-induced chronic colitis murine model in vivo. Findings: The expression of YAP/TAZ was significantly upregulated in stenotic fibroblasts, which was associated with the YAP/TAZ target gene signature. YAP/TAZ knockdown suppressed the activation of intestinal fibroblasts. In intestinal fibroblasts, YAP/TAZ were activated by the Rho-ROCK1 signalling pathway. High YAP/TAZ expression was positively correlated with ROCK1 expression, which is a prognostic marker for intestinal obstruction in CD patients. Interpretation: YAP/TAZ activation can lead to fibroblast activation and intestinal obstruction in CD. The effect of ROCK1 inhibitor on alleviating intestinal fibrosis is associated with YAP/TAZ inhibition. Targeted inhibition of YAP/TAZ in fibroblasts may be a potential therapeutic strategy to suppress intestinal fibrosis in CD. Funding: This work was supported by the National Key R&D Program of China (2019YFC1316002), the NSFC (81873547, 82073201, 81874177, 82000481) and the Shanghai Sailing Program (20YF1429400).

Motor stereotypic behaviors (MSBs) are common in captive rhesus macaques (Macaca mulatta) and human with psychiatric diseases. However, large gaps remain in our understanding of the molecular mechanisms that mediate this behavior and whether there are similarities between human and non-human primates that exhibit this behavior, especially at gene expression and gut microbiota levels. The present study combined behavior, blood transcriptome, and gut microbiota data of two groups of captive macaques to explore this issue (i.e., MSB macaques with high MSB exhibition and those with low: control macaques). Observation data showed that MSB macaques spent the most time on MSB (33.95%), while the CONTROL macaques allocated more time to active (30.99%) and general behavior (30.0%), and only 0.97% of their time for MSB. Blood transcriptome analysis revealed 382 differentially expressed genes between the two groups, with 339 upregulated genes significantly enriched in inflammation/immune response-related pathway. We also identified upregulated pro-inflammatory genes TNFRSF1A, IL1R1, and IL6R. Protein–protein interaction network analysis screened nine hub genes that were all related to innate immune response, and our transcriptomic results were highly similar to findings in human psychiatric disorders. We found that there were significant differences in the beta-diversity of gut microbiota between MSB and CONTROL macaques. Of which Phascolarctobacterium, the producer of short chain fatty acids (SCFAs), was less abundant in MSB macaques. Meanwhile, PICRUSTs predicted that SCFAs intermediates biosynthesis and metabolic pathways were significantly downregulated in MSB macaques. Together, our study revealed that the behavioral, gene expression levels, and gut microbiota composition in MSB macaques was different to controls, and MSB was closely linked with inflammation and immune response. This work provides valuable information for future in-depth investigation of MSB and human psychiatric diseases.

BackgroundAmine oxidase copper containing 1 (AOC1) is a gene whose biological function in colorectal cancer (CRC) has not been elucidated. Therefore, the purpose of this study was to investigate the clinical significance of AOC1 expression in CRC and its biological function in CRC cell lines.Materials and MethodsAOC1 expression levels were examined in paired CRC and peritumoral tissues, and distant liver metastatic tissues were examined using quantitative real-time PCR, western blotting, and immunohistochemistry staining. The log-rank test and Cox regression model were used to analyze the relationship between AOC1 expression and prognosis. Proliferation assays (Cell Counting Kit‐8 and colony formation assays), migration assays (Transwell and wound healing assays) and xenograft tumor formation in nude mice were performed to assess the biological role of AOC1 in CRC cells.ResultsAOC1 expression significantly increased in human CRC tissues, especially in liver metastases, and was associated with a worse prognosis. In addition, AOC1 had higher expression in tumor organoids than in normal organoids, suggesting that it was highly expressed in the tumor epithelium. Functional analysis demonstrated that AOC1 knockdown inhibited the proliferation and migration of CRC cells by inducing EMT in vitro. Xenograft tumor formation in nude mice showed that knockdown of AOC1 inhibited the tumor xenografts growth in vivo.ConclusionHigh expression of AOC1 was significantly associated with worse clinical outcomes, was an independent risk factor for poor prognosis, and promoted aggressive CRC cell phenotypes. AOC1 is expected to become a novel biomarker for predicting the prognosis of patients with CRC and an effective therapeutic target in clinical practice.

3-hydroxybutyrate dehydrogenase-2 (Bdh2), a short-chain dehydrogenase, catalyzes a rate-limiting step in the biogenesis of the mammalian siderophore, playing a key role in iron homeostasis, energy metabolism and apoptosis. However, the function of Bdh2 in embryonic stem cells (ESCs) remains unknown. To gain insights into the role of Bdh2 on pluripotency and cell fate decisions of mouse ESCs, we generated Bdh2 homozygous knockout lines for both mouse advanced embryonic stem cell (ASC) and ESC using CRISPR/Cas9 genome editing technology. Bdh2 deficiency in both ASCs and ESCs had no effect on expression of core pluripotent transcription factors and alkaline phosphatase activity, suggesting dispensability of Bdh2 for self-renewal and pluripotency of ESCs. Interestingly, cells with Bdh2 deficiency exhibited potency of endoderm differentiation in vitro; with upregulated endoderm associated genes revealed by RNA-seq and RT-qPCR. We further demonstrate that Bdh2 loss inhibited expression of multiple methyltransferases (DNMTs) at both RNA and protein level, suggesting that Bdh2 may be essentially required to maintain DNA methylation in ASCs and ESCs. Overall, this study provides valuable data and resources for understanding how Bdh2 regulate earliest cell fate decision and DNA methylation in ASCs/ESCs.