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Abstract Background Neuropsychiatric systemic lupus erythematosus (NPSLE) often manifests as cognitive deterioration, with activated microglia and blood-brain barrier (BBB) disruption implicated in these neurological complications. Wnt-inhibitory factor-1 (WIF-1), a secreted protein, has been detected in the cerebrospinal fluid (CSF) of NPSLE patients. However, the contribution of WIF-1 in contributing to lupus cognitive impairment remains poorly understood. Methods Using MRL/MpJ-Faslpr (MRL/lpr) lupus-prone mice and TLR7 agonist imiquimod (IMQ)-induced lupus mice, recombinant WIF-1 protein (rWIF-1) and adeno-associated virus (AAV) encoding sh-WIF-1 were administered via intracerebroventricular injection. Behavioral tests, histopathological examinations, flow cytometry, and molecular biology techniques were employed to investigate the underlying mechanisms. Results Microinjection of rWIF-1 exacerbated cognitive deficits and mood abnormalities, increased BBB leakage and neuronal degeneration, and caused aberrant activation of microglia and synaptic pruning in the hippocampus. Conversely, lupus mice injected with AAV-shWIF-1 exhibited significant remission. In vitro, rWIF-1 induced overactivation of microglia with an increased CD86+ pro-inflammatory subpopulation, upregulated phagocytic activity, and excessive synaptic engulfment, contributing to increased BBB permeability. Furthermore, WIF-1 exerted its biological effects through the CRYAB/STAT4 pathway, transcriptionally decreasing SHH production. We also identified that symmetric dimethylarginine (SDMA) could alleviate rWIF-1-induced microglial activation and BBB damage, thereby restoring SHH levels. Conclusions In conclusion, WIF-1 exacerbates lupus-induced cognitive dysfunction in mice by triggering aberrant microglial activation and BBB disruption through the CRYAB/STAT4-SHH axis, highlighting the potential therapeutic effects of SDMA for the treatment of NPSLE.

Abstract Subsea manifold system is a complex system that occupies a pivotal role in contemporary ocean engineering and has a significant impact on the safety of marine resource exploitation. Reliability technology plays a significant role in ensuring the safe operation of the subsea manifold system. To perform a comprehensive analysis of the reliability of complex systems, a combination method of FMECA-FFTA (Failure Modes, Effects and Criticality Analysis - Fuzzy Fault Tree Analysis) is introduced in this study. Firstly, FMECA is used to accomplish a qualitative analysis of system reliability considering multifactorial failure modes, which included analyzing potential failure modes, causes of system failure, and evaluating the degree of hazard to the system through a risk matrix diagram. Then, FFTA is applied to build a fault tree model to divide the system into “system-subsystem-component” and determine the minimal cut sets for quantitative analysis of system reliability. In addition, fuzzy set theory is incorporated to improve the accuracy of handling uncertainty in quantitative reliability analysis. Finally, a qualitative and quantitative reliability analysis is conducted by using FMECA-FFTA method for subsea manifold system. The failure modes of the subsea manifold system are clearly identified, including high-risk modes such as external leakage, medium-high-risk modes such as fail to close/lock on demand, and medium-risk modes such as leakage of critical location, plugged, and effective measures should be taken to focus on preventive protection and regular testing for the high risk, medium-high risk and medium risk modes.

With the development of global deepwater oil and gas and offshore wind power resources, there is an increasing demand for ultra-deep water pile hammers (UDPH). In this paper, a permanent magnet synchronous motor (PMSM) with oil fill is proposed for UDPH on the basis of underwater 2500 m depth and 450 kJ impact energy requirements. First, the rated parameters of the PMSM are calculated based on the power required by hydraulic pumps, and then, the method of combining empirical formulas and path algorithms is used to complete the electromagnetic scheme design. Second, finite element analysis of the electromagnetic field is carried out by Maxwell under both no-load and load conditions to verify the rationality of the PMSM. Furthermore, aiming at improving efficiency and reducing cogging, parameter optimization is carried out by a robust parameter optimization design method, and the optimal parameter scheme of the PMSM is obtained. In addition, loss analysis and temperature field coupling calculations of the optimized PMSM are conducted to verify that the temperature of this motor can meet the requirements under different working conditions. Finally, a comparative analysis is conducted between the proposed PMSM and the three-phase asynchronous motor used in the underwater 2,500 m-450 kJ UDPH. The results indicate that the new PMSM introduced in this paper demonstrates significant advantages in terms of weight, volume, and efficiency; moreover, the new PMSM is reasonable and more suitable for UDPH. Therefore, the PMSM proposed in this paper is reasonable and can provide a theoretical basis for improving the traditional UDPH.

Objective This study harnesses the power of text mining to quantitatively investigate the causative factors of falls in adult inpatients, offering valuable references and guidance for fall prevention measures within hospitals.Methods Employing KH Coder 3.0, a cutting-edge text mining software, we performed co-occurrence network analysis and text clustering on fall incident reports of 2,772 adult patients from a nursing quality control platform in a particular city in Jiangsu Province, spanning January 2017 to December 2022.Results Among the 2,772 patients who fell, 80.23% were aged above 60, and 73.27% exhibited physical frailty. Text clustering yielded 16 distinct categories, with four clusters implicating patient factors, four linking falls to toileting processes, four highlighting dynamic interplays between patients, the environment, and objects, and another four clusters revealing the influence of patient-caregiver interactions in causing falls.Conclusion This study highlights the complex, multifactorial nature of falls in adult inpatients. Effective prevention requires a collaborative effort among healthcare staff, patients, and caregivers, focusing on patient vulnerabilities, environmental factors, and improved care coordination. By strengthening these aspects, hospitals can significantly reduce fall risks and promote patient safety.

The small-diameter high-speed submersible permanent magnet synchronous motor (SHS-PMSM) is essential equipment for rodless oil and gas extraction in slimhole wells and high-water content oil wells. The SHS-PMSM typically operates for extended periods of time underground in high temperatures. Because of its compact size, the heat is difficult to dissipate, which increases the risk of motor overheating and damage. In order to accurately predict temperature, the method of magnetic-heat-flow multiphysics bidirectional coupling is studied in this paper. A SHS-PMSM with an outer diameter of ø89mm is taken as the object, and its copper loss, friction loss and convective heat transfer coefficient are studied by analytical derivation. The relationship between them and temperature are expressed by functions which can be compiled into User-Defined Functions (UDFs) as variable during the calculation process of finite volume method. Both coupling calculations and experiments are conducted. The temperature calculated by magnetic-heat-flow bidirectional connection is higher than that produced by the conventional method and more in line with experimental results after the results of both simulations and experiments are carried out and compared. The accuracy of the magnetic-heat-flow bidirectional coupling method is verified and the design basis of temperature for SHS-PMSM can be provided.

The ‘Okitsu No. 58’ citrus variety is highly prone to fruit cracking, which jeopardizes yield and results in economic losses. In this study, we investigated the impacts of spraying 5 distinct concentrations (0.1, 0.2, 0.3, 0.4, and 0.5 g/L) of chelated calcium (Ca) or silicon (Si) fertilizers at the young fruit stage (60-90 days after flowering, DAF) on fruit cracking and quality in the citrus variety ‘Okitsu No. 58’. The results showed either Ca or Si fertilizer treatments reduced fruit cracking. We found that all Ca and partial Si treatments (0.4 and 0.5 g/L) significantly promoted the accumulation of Ca content in the peel. Notably, Ca or Si treatments significantly reduced polygalacturonase (PG) activity and inhibited the production of water-soluble pectin (WSP) in the peel. Additionally, Ca or Si treatments elevated the superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) content of the peels. Changes in these parameters likely contributed to strengthening the durability of peel cell wall constituents, thus enhancing the fruit’s resistance to fruit cracking. Overall, except for the C3 (0.3 g/L of Ca), Ca or Si fertilizers contributed to fruit conventional quality, mainly in terms of higher soluble sugars (SS) and SS/TA (titratable acid). Therefore, our findings will provide a reference for the prevention and control of citrus fruit cracking and the development of new fertilizers.

Li-rich Mn-based oxides (LRMOs) hold great promise as next-generation cathode materials for high-energy Li-ion batteries because of their low cost and high capacity. Nevertheless, the practical application of LRMOs is impeded by their low initial Coulombic efficiency and rapid voltage decay. Herein, a V-doped layered-spinel coherent layer is constructed on the surface of a Co-free LRMO through a simple treatment with NH4VO3. The layered-spinel coherent layer with 3D ion channels enhanced Li+ diffusion efficiency, mitigates surface–interface reactions and suppresses irreversible oxygen release. Notably, V-doping significantly reduces the Bader charge of oxygen atoms, thereby impeding excessive oxidation of oxygen ions and further enhancing the stability of O-redox. The modified LRMO exhibites a remarkable initial Coulombic efficiency of 91.6%, significantly surpassing that of the original LRMO (74.4%). Furthermore, the treated sample showes an impressive capacity retention rate of 91.9% after 200 cycles, accompanied by a voltage decay of merely 0.47 mV per cycle. The proposed treatment approach is straightforward and significantly improves the initial Coulombic efficiency, voltage stability, and capacity stability of LRMO cathode materials, thus holding considerable promise for the development of high-energy Li-ion batteries.

Abstract Background Neuropsychiatric systemic lupus erythematosus (NPSLE), with various morbidities and multiple manifestations in the central nervous system, remains a limited standard for diagnosis. Our study was to discover novel biomarkers for improving the diagnostic efficiency for NPSLE. Methods We performed a quantitative planar protein antibody microarray to screen 1000 proteins in cerebrospinal fluid from controls, systemic lupus erythematosus (SLE, non-NPSLE) patients, and NPSLE patients. Differentially expressed proteins (DEPs) as candidate biomarkers were developed into a custom multiplexed protein antibody array for further validation in an independent larger cohort. Subsequently, we used least absolute shrinkage and selection operator regression (LASSO) analysis and multivariable logistic regression analysis for optimizing feature selection and constructing a diagnostic model. A receiver operating characteristic curve (ROC) was generated to assess the effectiveness of the models. Results The expression of 29 proteins in CSF was significantly altered in the comparison of the three groups. We selected 17 proteins as candidate biomarkers in accordance with protein interaction analysis. In the larger cohort, we identified 5 DEPs as biomarkers for NPSLE, including TCN2, CST6, KLK5, L-selectin, and Trappin-2. The diagnostic model included 3 hub proteins (CST6, TCN2, KLK5) and was best at discriminating NPSLE from SLE patients. These CSF biomarkers were also highly associated with disease activity. In addition, there were 6 molecules with remarkable changes in NPSLE CSF and hippocampus, which indicated the consistency of the environment in the brain and the promising molecular targets in the pathogenesis of NPSLE. Conclusions The dual-chips screening strategy demonstrated KLK5, L-selectin, Trappin-2, TCN2, and CST6 as CSF biomarkers for diagnosing NPSLE.

Abstract Aim Our study aimed at investigating the risk perception of nurses and related factors in the era of COVID‐19 period. Design Cross‐sectional study. Methods Four hundred and forty‐two participants completed an online questionnaire relating to their risk perception on public health emergencies. Data were collected between 25 November 2020 and 1 December 2020. Kruskal–Wallis test, Mann–Whitney U test and Ordinal logistic regression analysis were used to examine factors impacting on risk perception. Results 65.2% of nurses' risk perception of COVID‐19 was the moderate level even below the moderate level in the postperiod of COVID‐19. Kruskal–Wallis test results indicated significant differences in gender, age, education status, working years, professional title, postlevel, COVID‐19 contact experience, marital status and health status (p

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with significant clinical implications. Emerging research indicates endoplasmic reticulum (ER) stress as a critical pathogenic factor governing inflammatory responses, lipid metabolism and insulin signal transduction in patients with NAFLD. ER stress-associated activation of multiple signal transduction pathways, including the unfolded protein response, disrupts lipid homeostasis and substantially contributes to NAFLD development and progression. Targeting ER stress for liver function enhancement presents an innovative therapeutic strategy. Notably, the natural bioactive compounds of plant extracts have shown potential for treating NAFLD by reducing the level of ER stress marker proteins and mitigating inflammation, stress responses, and de novo lipogenesis. However, owing to limited comprehensive reviews, the effectiveness and pharmacology of these bioactive compounds remain uncertain. Objectives: To address the abovementioned challenges, the current review categorizes the bioactive compounds of plant extracts by chemical structures and properties into flavonoids, phenols, terpenoids, glycosides, lipids and quinones and examines their ameliorative potential for NAFLD under ER stress. Methods: This review systematically analyses the literature on the interactions of bioactive compounds from plant extracts with molecular targets under ER stress, providing a holistic view of NAFLD therapy. Results: Bioactive compounds from plant extracts may improve NAFLD by alleviating ER stress; reducing lipid synthesis, inflammation, oxidative stress and apoptosis and enhancing fatty acid metabolism. This provides a multifaceted approach for treating NAFLD. Conclusion: This review underscores the role of ER stress in NAFLD and the potential of plant bioactive compounds in treating this condition. The molecular mechanisms by which plant bioactive compounds interact with their ER stress targets provide a basis for further exploration in NAFLD management.

Human–wildlife conflicts are becoming increasingly common worldwide and are a challenge to biodiversity management. Compared with compensatory management, which often focuses on solving emergency conflicts, mitigation management allows decision-makers to better understand where the damage is distributed, how the species are distributed and when the species conduct their activity. Here, we integrated data collected from 90 districts/counties’ damage surveys and 1271 camera traps to understand the damage status, abundance, density and activity rhythms of wild boar (Sus scrofa) in Zhejiang, Eastern China, from January 2019 to August 2023. We found that (1) wild boar–human conflicts were mainly distributed in the northwest and southwest mountainous regions of Zhejiang Province; (2) the total abundance of wild boar was 115,156 ± 24,072 individuals, indicating a growing trend over the past decade and a higher density in the western and southern regions; (3) wild boar exhibited different activity patterns across different damage regions, and the periods around 7:00, 11:00 and 16:00 represented activity peaks for wild boar in seriously damaged regions. The damage distribution, density, distribution and activity rhythms provide specific priority regions and activity intensity peaks for conflict mitigation. We believe that these findings based on the damage, distribution and activity could provide a scientific basis for mitigation management at the county level and enrich the framework of human–wildlife conflict mitigation.

IntroductionSepsis is a vitally serious disease leading to high mortality. Nucleated red blood cells (NRBCs) are present in some noninfectious diseases, but the relationship between NRBCs and sepsis in children remains unknown. The purpose of this study was to compare the clinical characteristics and outcomes of sepsis with positive NRBCs and negative NRBCs in children, and to further explore whether the count of NRBCs has a relationship with the severity of sepsis.MethodsWe enrolled children with sepsis who were admitted to the Children’s Hospital of Chongqing Medical University between January 2020 and December 2022. The children’s clinical data, laboratory data and outcomes were recorded and analyzed.ResultsOne hundred and fifteen children met the inclusion criteria in our study. Compared to negative NRBCs patients, the C-reactive protein, alanine transaminase, urea nitrogen values, mortality rate and length of hospitalization were found to be significantly increased, while platelet counts, and hemoglobin were significantly decreased in sepsis patients with positive NRBC (P < 0.05). Receiver operating characteristic (ROC) curves analysis showed that the optimal cutoff value of the NRBC count in the diagnosis of severe sepsis was 3, with a sensitivity of 87.5% and specificity of 94.9%. The area under the ROC curve was 0.877 (95% CI: 0.798-0.957).DiscussionThese findings demonstrated that NRBC count has the potential to be a biomarker for the diagnosis of sepsis in children, especially an NRBC count greater than 3, which may predict the severity and poor prognosis in children suffering from sepsis.

Purpose: To compare the safety, feasibility, and effectiveness of transvaginal natural orifice transluminal endoscopic sacrocolpopexy (vNOTES-SC) and laparoendoscopic single-site sacrocolpopexy (LESS-SC) for pelvic organ prolapse (POP). Method: Ninety-four patients with POP who underwent vNOTES-SC or LESS-SC from October 2016 to November 2018 were included. The propensity score matching method was used for 1:1 matching between the two surgery groups. After matching, the general perioperative indicators, surgical complications, and the subjective and objective therapeutic effects of the two groups 3 years post-surgery were analyzed. Results: After matching, 36 patients in each group were included, exhibiting balanced and comparable baseline data and an average follow-up of 48.6 ± 7.44 months. The operation time and postoperative hospitalization days were significantly reduced in the vNOTES-SC group (P 0.05). Additionally, no significant differences were detected in de novo stress urinary incontinence (16.7% vs. 13.9%), de novo overactive bladder (de novo OAB, 8.3% vs. 0.0%), urination disorder (2.8% vs. 0.0%), defecation disorder (0.0% vs. 2.8%), lumbosacral pain (0.0% vs. 2.8%), or mesh complication (2.8% vs. 5.6%) incidences between the vNOTES-SC and LESS-SC groups (P > 0.05). Prolapse recurrence was not reported in either group. The quantitative description of pelvic organ position (POP-Q), Pelvic Floor Impact Questionnaire-7 (PFIQ-7), and Patient Global Impression of Improvement scale (PGI-I) scores showed improvement after the operation, but no significant differences were observed between the two groups (P > 0.05). Conclusion: The 3-year follow-up revealed that vNOTES-SC and LESS-SC had similar complications and efficacy rates. Compared with LESS-SC, vNOTES-SC resulted in shorter operation time and fewer postoperative hospitalization days (corresponding to the enhanced recovery after surgery [ERAS] concept), along with better cosmetic results without a scar. Therefore, our study findings suggest that clinicians should choose the surgery method based on the specific situation, and we recommend choosing vNOTES-SC when both surgeries are suitable.

Mesenchymal stem cells (MSCs), multipotent stromal cells, have attracted extensive attention in the field of regenerative medicine and cell therapy due to the capacity of self-renewal, multilineage differentiation, and immune regulation. MSCs have different cellular effects in different diseases, and even have markedly different curative effects with different tissue sources, indicating the plasticity of MSCs. The phenotypes, secreted factors, and proliferative, migratory, differentiating, and immunomodulatory effects of MSCs depend on certain mediators present in their microenvironment. Understanding microenvironmental factors and their internal mechanisms in MSC responses may help in subsequent prediction and improvement of clinical benefits. This review highlighted the recent advances in MSC plasticity in the physiological and pathological microenvironment and multiple microenvironmental factors regulating MSC plasticity. It also highlighted some progress in the underlying molecular mechanisms of MSC remodeling in the microenvironment. It might provide references for the improvement in vitro culture of MSCs, clinical application, and in vivo induction.

BackgroundThe aim of this study was to assessment the efficacy and safety of Programmed cell death protein 1 (PD-1)/Programmed cell death-Ligand protein 1 (PD-L1) inhibitors plus anti-angiogenic agents with or without chemotherapy versus PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment for patients with advanced non-small cell lung cancer.MethodsIn this study, pre-treatment clinical and laboratory indicators from 73 patients with advanced non-small cell lung cancer were retrieved for retrospective analysis. According to the therapy regimes they received, the patients were separated into groups, PD-1/PD-L1 inhibitors plus chemotherapy group (PC group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents’ group (PA group), PD-1/PD-L1 inhibitors plus anti-angiogenic agents plus chemotherapy group (PAC group). Cox’s proportional hazards regression model and Kaplan-Meier (KM) curves were used to assess the connection between treatment regimens and progression free survival (PFS) and overall survival (OS). In addition, the association of treatment regimens with the risk of disease progression and death was evaluated by subgroup analysis.ResultsThe average age of the enrolled patients was 58.2 ± 10.2 years and 75.3% were male. Multivariate analyses showed that patients in PA group (Disease progression: HR 0.4, P=0.005. Death: HR 0.4, P=0.024) and PAC group (Disease progression: HR 0.3, P=0.012. Death: HR 0.3, P=0.045) had a statistically significant lower hazard ratio (HR) for disease progression and death compared to patients in PC group. Kaplan-Meier analysis showed that patients in PA group (mPFS:7.5 vs.3.5, P=0.00052. mOS:33.1 vs.21.8, P=0.093) and PAC group (mPFS:5.1 vs.3.5, P=0.075. mOS:37.3 vs.21.8, P=0.14) had a longer PFS and OS compared to patients in PC group. In all the pre-defined subgroups, patients in PA and PAC groups showed a decreasing trend in the risk of disease progression and death in most subgroups. The patients in PA group (DCR:96.3% vs.58.3%, P=0.001) and PAC group (DCR:100% vs.58.3%, P=0.019) had a better disease control rate (DCR) than patients in PC group.ConclusionPD-1/PD-L1 inhibitors plus anti-angiogenic agents with or without chemotherapy were superior to PD-1/PD-L1 inhibitors plus chemotherapy as second or later-line treatment in patients with advanced non-small cell lung cancer.

Diffuse pulmonary hemorrhage (DPH) is a common respiratory complication in patients with systemic lupus erythematosus (SLE). Our previous study found that myeloid-derived suppressor cells (MDSCs) have an important role in SLE pathogenesis. In this study, we further examined the role of MDSCs in the DPH mice model. We first observed an increased proportion of MDSCs and impaired immunosuppressive function in bronchoalveolar lavage fluid (BALF) and peritoneal cavity in the DPH mice model induced by pristane. By injecting anti-Gr-1 antibody, we found that MDSCs clearance can significantly alleviate DPH symptoms. The detection of downstream molecules proved that the mTOR signaling pathway was obviously activated in purified DPH MDSCs. After treatment of DPH model mice with AMPK agonist metformin, mammalian target of rapamycin (mTOR) inhibitor INK128, and rapamycin, respectively, we observed that inhibition of the mTOR signal alleviated DPH symptoms, inhibited the expansion of mononuclear MDSCs (M-MDSCs) and the differentiation of pro-inflammatory M1 macrophages (M1), which, in turn, promoted the expansion of granulocytes MDSCs (G-MDSCs) and differentiation of anti-inflammatory M2 macrophages (M2). We then demonstrated that inhibition of the mTOR signal increased the expansion of G-MDSCs, promoted M-MDSCs differentiation into M2 and inhibited their differentiation into M1 by administering TLR7 agonist R848 in vitro to simulate lupus environment. In addition, we also observed increased forkhead box-O1 (FoxO1) expression in M-MDSCs and macrophages after mTOR signal inhibition, both in vivo and in vitro. After down-regulation of FoxO1 by siRNA transfection, the regulatory effects of mTOR signal inhibition on M-MDSCs, M1 and M2 were reversed. Taken together, inhibition of the AMPK/mTOR signal could alleviate lupus-like diffuse lung injury by inducing M-MDSCs to differentiate into M2 by up-regulating FoxO1.

Abstract Background Few clinical research studies with long‐term follow‐up have revealed whether cardiopulmonary bypass (CPB) increases the risk of postoperative distant metastasis in patients with giant refractory thoracic tumors. The present study evaluated the risk of distant metastasis after surgery utilizing CPB with long‐term follow‐up. Methods Clinical data for patients with giant refractory thoracic tumors who underwent resection with the use of CPB in the Second Affiliated Hospital of Soochow University during the past 11 years were retrospectively reviewed. Results Of the 14 patients with giant refractory thoracic tumors who had undergone surgery under CPB, 10 patients (71.4%) were completely resected. Twelve patients were followed up for 13–127 months with 10 patients were completely resected and two patients could not be completely resected due to severe tissue invasion. Three patients (25%) suffered from distant metastasis, and four patients (33.3%) experienced local recurrence. Only one patient (1/10) with complete resection suffered from distant metastasis, while two patients (2/10) experienced local recurrence. Two patients (2/2) with major resection suffered from both distant metastasis and local recurrence. Median overall survival for patients who have been regularly followed up was 50 months with 1‐, 5‐, and 10‐year survival of 100%, 75%, and 66.7%. No difference was found between the distant metastasis survival and the local recurrence survival. (p = 0.99). Conclusions CPB is an effective strategy for complete resection of the giant refractory thoracic tumors with an acceptable risk of postoperative distant metastasis for some patients.

Abstract Background Neuropsychiatric systemic lupus erythematosus (NPSLE) is a severe complication, which involves pathological damage to the brain and cognitive function. However, its exact mechanism of action still remains unclear. In this study, we explored the role of microglia in the cognitive dysfunction of NPSLE mice. We also analyzed and compared the metabolites in the hippocampal tissues of the lupus model and control mice. Methods MRL/MpJ-Faslpr (MRL/lpr) female mice were used as the NPSLE mouse model. Metabolomics was used to assess hippocampal glycolysis levels. Glucose, lactic acid, IL-6, and IL-1β of the hippocampus were detected by ELISA. Based on the glycolysis pathway, we found that pyruvate kinase isoform M2 (PKM2) in the hippocampus was significantly increased. Thus, the expression of PKM2 was detected by qRT-PCR and Western blotting, and the localization of PKM2 in microglia (IBA-1+) or neurons (NeuN+) was assessed by immunofluorescence staining. Flow cytometry was used to detect the number and phenotype of microglia; the changes in microglial phagocytosis and the β-catenin signaling pathway were detected in BV2 cells overexpressing PKM2. For in vivo experiments, MRL/lpr mice were treated with AAV9-shPKM2. After 2 months, Morris water maze and conditional fear tests were applied to investigate the cognitive ability of mice; H&E and immunofluorescence staining were used to evaluate brain damage; flow cytometry was used to detect the phenotype and function of microglia; neuronal synapse damage was monitored by qRT-PCR, Western blotting, and immunofluorescence staining. Results Glycolysis was elevated in the hippocampus of MRL/lpr lupus mice, accompanied by increased glucose consumption and lactate production. Furthermore, the activation of PKM2 in hippocampal microglia was observed in lupus mice. Cell experiments showed that PKM2 facilitated microglial activation and over-activated microglial phagocytosis via the β-catenin signaling pathway. In vivo, AAV9-shPKM2-treated mice showed decreased microglial activation and reduced neuronal synapses loss by blocking the β-catenin signaling pathway. Furthermore, the cognitive impairment and brain damage of MRL/lpr mice were significantly relieved after microglial PKM2 inhibition. Conclusion These data indicate that microglial PKM2 have potential to become a novel therapeutic target for treating lupus encephalopathy.

Pseudomonas aeruginosa is an opportunistic pathogenic bacterium that causes various acute and chronic lung infections in immunocompromised patients. We previously found that a quorum sensing (QS) signal, namely, autoinducer-2 (AI-2), facilitates the pathogenicity of the wild-type (WT) P. aeruginosa PAO1 strain in vitro and in vivo. However, the immunological mechanism that leads to pulmonary injury remains to be elucidated. In this study, we aimed to investigate the effects of AI-2 on interleukin-17A (IL-17A) production during acute P. aeruginosa PAO1 lung infection using a mouse model, with an emphasis on the underlying immunological mechanism. Compared to infection with P. aeruginosa PAO1 alone, infection with P. aeruginosa PAO1 combined with AI-2 treatment resulted in significantly increased levels of IL-17A, numbers of Th17 cells and levels of STAT3 in the lung tissues of WT mice (P < 0.05), as well as more serious lung damage. In contrast, the concentrations of the proinflammatory cytokines IL-1α, IL-1β, and IL-6 and the chemokine keratinocyte-derived chemokine (KC) were significantly reduced during P. aeruginosa lung infection in IL-17A−/− mice compared with WT mice (P < 0.05), and no effects were observed after AI-2 treatment (P > 0.05). Furthermore, the level of IL-17A in the lungs of WT mice was significantly reduced following infection with a P. aeruginosa strain harboring mutations in the QS genes lasR and rhlR compared with the level of IL-17A following infection with P. aeruginosa PAO1. Our data suggest that AI-2 promotes P. aeruginosa PAO1 acute lung infection via the IL-17A pathway by interfering with the QS systems of P. aeruginosa. IL-17A may be a therapeutic target for the treatment of acute P. aeruginosa lung infections in the clinic.

ObjectivesTo study the effect of parecoxib sodium (PS) application, combined with enhanced recovery after surgery (ERAS) nursing, on inflammation and knee joint function in elderly patients after total knee arthroplasty (TKA).MethodsIn this prospective cross-sectional study, we recruited 120 elderly patients treated with TKA who were randomly divided into two groups, the combine group and the control group, with 60 patients in each group. Patients in the control group received ERAS nursing and normal saline, and the patients in the combine group received ERAS nursing and PS. At different times after surgery, we compared the hemoglobin (Hb), complete white blood cell count (WBC), erythrocyte sedimentation rate (ESR), and serum IL-1β, TNF-α, and IL-6, and recovery time for different ranges of joint motion and the knee joint function HSS (hospital for special surgery scale) score between the two groups.ResultsOn the third and seventh postoperative days, the levels of Hb in the patients of the combine group were significantly lower than those in the control group (p

Based on the key module-lifting arm system, based on the principle of similarity and the hydrodynamic experimental method of a multi-dimension vibration test platform, an experimental platform for dismantling equipment is designed and built. Subsequently, the motion control model of the six-degrees-of-freedom platform is established. The three-ring control model of a servo electric cylinder is established, and the active heave compensation control of a servo electric cylinder is realized by combining position control theory. Based on the co-simulation of ADAMS and Simulink, the co-simulation system of the integrated dismantling equipment experimental platform is designed and built, and the simulation system is tested and verified. Finally, simulation and experimental verification are carried out based on the experimental platform and co-simulation system. The results show that the heave compensation rate reaches 58.3% in third-class sea conditions, 61.2% in fourth-class sea conditions, and 62.4% in fifth-class sea conditions. The integrated dismantling scheme of super large offshore oilfield facilities is feasible but, in order to ensure the safety and reliability of the operation, a heave compensation system needs to be added. The error between the simulation results and the experimental results is about 15%. Based on the analysis of external interference factors in the experiment, the error results are within a reasonable range, which proves that the experimental platform, the co-simulation system of the experimental platform, and the heave compensation strategy are accurate and effective. This study, for the first time in China, provides an effective experimental platform and co-simulation platform for the design and optimization of the integrated dismantling equipment of super large offshore oilfield facilities and lays a good research foundation for the construction and engineering demonstration of subsequent equipment.

Abstract Background Necroptosis is a form of regulated necrosis that is involved in various autoimmune diseases. Mixed lineage kinase domain-like pseudokinase (MLKL) has been identified as a key executor of necroptosis; however, the significance of MLKL in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) has not been investigated. In this study, we aimed to determine the mRNA level of MLKL in PBMCs and examine its relationship with clinical features and serological parameters in SLE. Methods Real-time transcription-polymerase chain reaction (RT-PCR) analysis was used to determine the expression of MLKL mRNA in PBMCs from 59 patients with SLE, 25 patients with rheumatoid arthritis (RA), and 30 age- and sex-matched healthy controls (HC). Spearman’s correlation test was performed to assess the correlation of MLKL mRNA with clinical variables. The receiver operating characteristic (ROC) curve was created to evaluate the diagnostic value. Results Our results showed MLKL mRNA in PBMCs was upregulated in SLE patients compared to that in RA and HC individuals. SLE patients positive for antinuclear antibodies had significantly higher MLKL mRNA than antibody-negative patients. In SLE patients, MLKL mRNA was found to be upregulated in patients with lupus nephritis (LN) as compared with patients without LN, and also higher in active patients than in stable patients. MLKL mRNA level was significantly and positively correlated with c-reaction protein (CRP) (r = 0.3577, p = 0.0237), erythrocyte sedimentation rate (ESR) (r = 0.4091, p = 0.0043), serum immunoglobulin G (IgG) concentration (r = 0.3546, p = 0.0289), and the numbers of positive antinuclear antibodies (ANAs) (r = 0.3945, p = 0.0432). ROC analysis showed that MLKL mRNA in PBMCs had an area under the curve of 0.9277 (95% CI 0.8779–0.9775, p

Abstract Background Long control region (LCR) of human papillomavirus (HPV) has shown multiple functions on regulating viral transcription. The variations of LCR related to different lineages/sub-lineages have been found to affect viral persistence and cervical cancer progression differently. In this study, we focused on gene polymorphism of HPV16/18/58 LCR to assess the effect variations caused on transcription factor binding sites (TFBS) and provided more data for further study of LCR in Southwest China. Methods LCR of HPV16/18/58 were amplified and sequenced to do polymorphic and phylogenetic anlysis. Sequences of each type were aligned with the reference sequence by MEGA 6.0 to identify SNPs. Neighbor-joining phylogenetic trees were constructed using MEGA 6.0. Transcription factor binding sites were predicted by JASPAR database. Results The prevalence of these three HPVs ranked as HPV16 (12.8%) > HPV58 (12.6%) > HPV18 (3.5%) in Chengdu, Southwest China. 59 SNPs were identified in HPV16-LCR, 18 of them were novel mutations. 30 SNP were found in HPV18-LCR, 8 of them were novel. 55 SNPs were detected in HPV58-LCR, 18 of them were novel. Also, an insertion (CTTGTCAGTTTC) was detected in HPV58-LCR between position 7279 and 7280. As shown in the neighbor-joining phylogenetic trees, most isolates of HPV16/18/58 were clustered into lineage A. In addition, one isolate of HPV16 was classified into lineage C and 3 isolates of HPV58 were classified as lineage B. JASPAR results suggested that TFBS were potentially influenced by 7/6 mutations on LCR of HPV16/18. The insertion and 5 mutations were shown effects in LCR of HPV58. Conclusion This study provides more data for understanding the relation among LCR mutations, lineages and carcinogenesis. It also helps performing further study to demonstrate biological function of LCR and find potential marker for diagnosis and therapy.

Background: The relationship between dietary patterns and atherosclerosis is inconclusive. Usually, diets vary greatly among different regions due to cultural differences and lifestyles. Few studies to date based on a Chinese population have investigated the relationship between dietary patterns and the formation of atherosclerosis in carotid arteries. We aimed to investigate whether dietary patterns were related to carotid atherosclerosis among an adult population in Tianjin, China.Methods: This cross-sectional study included a total of 2,346 participants aged 50 years or older (mean: 59.7 ± 6.29 years). Dietary intakes were assessed using a validated 81-item semiquantitative food frequency questionnaire, and factor analysis was used to identify dietary patterns. Carotid atherosclerosis was defined as a common carotid artery intima-media thickness ≥1.0 mm or plaques, or a carotid bifurcation intima-media thickness ≥1.2 mm. Multiple logistic regression models were used to explore the relationship between dietary patterns and carotid atherosclerosis.Results: Three factors were determined: “health” dietary pattern (factor 1), “traditional Tianjin” dietary pattern (factor 2), and “sweets” dietary pattern (factor 3). The multivariable-adjusted odds ratios (95% CI) of carotid atherosclerosis for the increasing quartiles of the sweets dietary pattern scores in women were as follows: 1.00 (reference), 1.33 (0.91, 1.97), 1.21 (0.82, 1.79), 1.64 (1.08, 2.51) (p for trend

Objective: Acute poisoning in children is characterized by regional differences. This study described the basic situation of childhood poisoning in southwest China based on hospitalized cases.Data and Methods: A total of 1,076 acute poisoning cases among hospitalized children admitted to Children's Hospital of Chongqing Medical University from January 2012 to December 2020 were included in this study. Clinical data such as gender, age, living environment, poisonous substance, and cause of poisoning were statistically described. Trends of length of hospital stay, population distribution, poisonous substances, and causes of acute poisoning in the hospitalized children were compared over time.Results: The cohort comprised 588 males and 488 females; 811 cases lived in rural areas and the rest resided in urban areas. Most cases were between early childhood and school age. Poisoning usually occurred at home (973 cases, 90.4%). Pesticides (381 cases, 35.4%) and drugs (275 cases, 25.6%) were the two most common poisonous substances. Two main causes of poisoning were accidental taking (755 cases, 70.2%) and suicide (177 cases, 16.4%). The results of univariate analysis of suicide showed significant correlations among gender, place of residence, age, poisonous substance, and place of suicide (P < 0.001), while living environment (town), age (adolescence), and poisonous substance (pesticide, drug) were independent risk factors (P < 0.05). There was no significant change in the length of hospital stay for poisoning over time. The overall number of hospitalizations presented a decreasing trend, while the number of urban children gradually increased. The proportion of adolescent poisoned children and suicidal children increased in the last 3 years.Conclusion: Optimizing the package and distribution channels of pesticides and drugs, raising safety awareness of children to avoid accidental injuries, and paying attention to children's mental health are measures that are necessary to prevent poisoning in children.

Cigarette smoke induces microRNA dysregulation in cancers. Here, the authors show that cigarette smoke promotes the maturation of oncogenic primary miR-25 due to METTL3 hypomethylation, and mature miR-25 suppresses PH domain leucine-rich repeat protein phosphatase 2, resulting in oncogenic AKT activation in pancreatic cancer.

Abstract Background Breast cancer is one of the most common malignancies and the major cause of cancer-related death in women. Although the importance of PIWI-interacting RNAs (piRNAs) in cancer has been increasingly recognized, few studies have been explored the functional mechanism of piRNAs in breast cancer development and progression. Methods We examined the top 20 highly expressed piRNAs based on the analysis of TCGA breast cancer data in two patient cohorts to test the roles of piRNAs in breast cancer. The effects of piRNA-36,712 on the malignant phenotypes and chemosensitivity of breast cancer cells were detected in vitro and in vivo. MS2-RIP and reporter gene assays were conducted to identify the interaction and regulation among piRNA-36,712, miRNAs and SEPW1P. Kaplan-Meier estimate with log-rank test was used to compare patient survival by different piRNA-36,712 expression levels. Results We found piRNA-36,712 level was significantly lower in breast cancer than in normal breast tissues and low level was correlated with poor clinical outcome in patients. Functional studies demonstrated that piRNA-36,712 interacts with RNAs produced by SEPW1P, a retroprocessed pseudogene of SEPW1, and subsequently inhibits SEPW1 expression through competition of SEPW1 mRNA with SEPW1P RNA for microRNA-7 and microRNA-324. We also found that higher SEPW1 expression due to downregulation of piRNA-36,712 in breast cancer may suppress P53, leading to the upregulated Slug but decreased P21 and E-cadherin levels, thus promoting cancer cell proliferation, invasion and migration. Furthermore, we found that piRNA-36,712 had synergistic anticancer effects with the paclitaxel and doxorubicin, two chemotherapeutic agents for breast cancer. Conclusions These findings suggest that piRNA-36,712 is a novel tumor suppressor and may serve as a potential predictor for the prognosis of breast cancer patients.

Background: Ghrelin is the endogenous ligand of growth hormone secretagogue receptor 1a, which plays a role in regulating immunity and inflammation. The aim of this study is to assess the diagnostic value of plasma ghrelin in sepsis-associated pediatric acute respiratory distress syndrome (PARDS).Methods: We recruited patients who were admitted to the pediatric ICU (PICU) of the Children's Hospital of Chongqing Medical University between January 2019 and January 2020 and met the diagnostic criteria for sepsis. Data on clinical variables, laboratory indicators, plasma ghrelin concentrations, and inflammatory factors were collected and evaluated, and patients were followed up for 28 days. The area under the receiver-operating characteristic curves (AUROC) were determined using logistic regression to calculate and test cut-off values for ghrelin as a diagnostic indicator of sepsis-associated PARDS. The log-rank test was used to compare survival according to ghrelin levels.Main results: Sixty-six PICU patients (30 with ARDS and 36 without ARDS) who met the diagnostic criteria of sepsis were recruited. The ghrelin level was significantly higher in the ARDS group than in the non-ARDS group. The AUROC of ghrelin was 0.708 (95% confidence interval: 0.584–0.833) and the positivity cutoff value was 445 pg/mL. Sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of plasma ghrelin for the diagnosis of PARDS-associated sepsis were 86.7, 50.0, 59.1, 81.8, 1.734, and 0.266%, respectively. The survival rate of sepsis patients were significantly improved when the ghrelin level was >445 pg/mL.Conclusions: Ghrelin plasma levels were higher in sepsis-associated PARDS, and accompanied by increased levels of inflammatory factors. High ghrelin levels are a positive predictor of ICU survival in sepsis patients. Yet, there is no evidence to prove that elevated ghrelin is a promising diagnostic indicator of sepsis-associated PARDS.Trial registration: Clinicaltrials, ChiCTR1900023254. Registered 1 December 2018 - Retrospectively registered, http://www.clinicaltrials.gov/ChiCTR1900023254.

Objective To investigate the prognostic value of pretreatment haemoglobin-to-red cell distribution width radio (HRR) in predicting overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC). Methods This retrospective study analysed patients with advanced NSCLC. Kaplan–Meier survival analysis and Cox proportional hazards regression analysis were conducted to evaluate the predictive value of HRR for OS. A propensity matching analysis was used to reduce the impact of other confounding factors on the results. Results A total of 448 patients were enrolled in the study. The median HRR was 0.984, which was used as the cut-off value. Regardless of matching or not, a lower HRR was correlated with an unfavourable risk of death. After propensity matching, univariate and multivariate analysis showed that HRR was an independent factor for the prognosis of NSCLC (hazard ratio [HR] 1.55, 95% confidence interval [CI] 1.17, 2.04; HR 1.57, 95% CI, 1.17, 2.10; respectively). Kaplan–Meier analysis showed that low HRR was associated with shortened OS. The relationship between HRR and the risk of death was consistent across all patient subgroups after stratification by subgroup analysis. Conclusions These findings showed that a lower pretreatment HRR could be a potentially valuable prognostic factor in patients with advanced NSCLC.

Objective To evaluate the prognostic accuracy of d -dimer levels for advanced non-small-cell lung cancer (NSCLC). Methods This retrospective cohort study included 651 patients initially diagnosed with advanced NSCLC. Patients with d -dimer levels ≥0.5 mg/L were included in the high d -dimer group, whereas patients with lower levels were included in the normal group. Cumulative survival was estimated using Kaplan–Meier curves and compared using the log-rank test. Multivariate analyses were performed using the Cox proportional hazards model. Results The median plasma d -dimer level in the study cohort was 0.61 ± 0.49 mg/L. d -dimer levels were elevated in 60.98% of patients, and 80.1% of such patients had adenocarcinoma. Univariate and multivariate analyses identified d -dimer content as an independent factor for the prognosis of NSCLC (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.19–1.98). Kaplan–Meier analysis revealed that high plasma d -dimer levels were associated with shorter overall survival (HR = 1.48, 95% CI = 1.19–1.84). In addition, the receipt of 2 lines. Conclusion The present results imply that pretreatment plasma d -dimer levels could represent a prognostic factor for advanced NSCLC.

Blood orange (Citrus sinensis L. Osbeck) is a rare commercial citrus fruit containing abundant anthocyanins and has numerous health benefits. Blood orange rootstock determines the fruit yield and quality. This study evaluated the effect of the three most commonly used rootstocks on the fruit features, color index, physicochemical parameters, anthocyanin accumulation, the anthocyanin biosynthetic gene expression, and the associated enzymes during the fruit development and ripening of ‘Tarocco’ blood orange. The highest anthocyanin content at harvest was found in blood orange trees grafted onto ‘Trifoliate orange’ (Poncirus trifoliata L. Raf., Pt) rootstock. Molecular analyses revealed that the rootstock affects the anthocyanin accumulation in the blood orange. Additionally, there was a strong correlation between the anthocyanin content and the expression and the activity of related genes and enzymes, respectively. Based on gene expression and enzymatic activity analyses, Pt rootstock promotes a very high anthocyanin accumulation in ‘Tarocco’ blood orange fruit. Accordingly, Pt is the promising rootstock for producing good quality and highly nutritious ‘Tarocco’ blood orange fruit for commercial purposes.

Abstract Background Hand-foot-mouth disease (HFMD) is an acute infectious disease caused by enteroviruses, and HFMD complicated by cardiopulmonary failure has a high mortality. B type natriuretic peptide (BNP) is widely applied in monitoring cardiovascular disorders, and thus, we investigated whether this index was associated with the severity of HFMD and the outcome in severe HFMD. Methods Serum BNP, lactate, and glucose levels as well as white blood cell (WBC) count, PaO2/FiO2, and cardiac output (CO) were analyzed in the 83 enrolled HFMD patients according to different conditions (common, severe, and critical; with and without complication; and survivors and non-survivors). The control group consisted of 29 patients with respiratory tract infections. Results No significant differences in CO were observed between the groups. Serum lactate, glucose, BNP, and WBC levels in the critical group were significantly higher than those in the severe, common, and control groups (p

OBJECTIVE:This meta-analysis aimed to investigate the efficacy and safety of plastic wrap applied after birth and during NICU in preterm infants for prevention of heat loss in preterm infants. STUDY METHODS:The Medline (1950 to August 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7, 2015), CINAHL (1982 to August 2015) and the Embase (1974 to August 2015) databases were searched for randomized controlled trials (RCTs) or quasi-RCTs with main outcomes related to the core temperature (baseline temperature and/or post-stabilization temperature), hypothermia, mortality rate and hyperthermia. RESULT:The included studies were of low to moderate quality. Compared with unwrapped infants, plastic wrap was associated with a significantly higher baseline temperature and post-stabilization temperature both in infants < 28 weeks of gestation (mean difference [MD] = 0.62, 95% CI 0.38 to 0.85; MD = 0.41, 95% CI 0.33 to 0.50, respectively), and in infants between 28 to 34 weeks of gestation (MD = 0.54, 95% CI 0.21 to 0.87; MD = 0.64, 95% CI 0.45 to 0.82, respectively). Use of plastic wrap was associated with lower incidence of hypothermia (relative risk [RR] = 0.70, 95% CI 0.63 to 0.78). However, use of plastic wrap in preterm infants was not associated with decrease in mortality (RR: 0.88, 95% CI 0.70 to 1.12, P = 0.31). Incidence of hyperthermia was significantly higher in the plastic wrap group as compared to that in the control group (RR = 2.55, 95% CI: 1.56 to 4.15, P = 0.0002). Hyperthermia in the plastic wrap group was resolved within one or two hours after unwrapping the babies. CONCLUSION:Plastic wrap can be considered an effective and safe additional intervention to prevent hypothermia in preterm infants. However, its cost-effectiveness and long-term effect on mortality needs to be ascertained by conducting well-designed studies with longer follow-up period.

Marine unbonded flexible pipes serve as the most essential equipment in offshore oil and gas exploration and exploitation. Axial compressive loads during installation or in service in the complex marine environment usually lead to buckling failure. A flexible pipe is a composite structure with multiple functional layers, of which the tensile armor layer plays a key role with regard to the response of the pipe subjected to axial loads. In this paper, a simplified three-dimensional finite element model is developed, focusing on the tensile layer and replacing the carcass layer, pressure sheath layer, and pressure armor layer by a cylindrical rigid body to reduce computational expense. By using this model, the buckling failure modes of the tensile armor layer (in particular the birdcaging phenomenon) are analyzed. Several key parameters that affect the stability of the flexible pipe under axial compression and torsion are emphasized, and their effects on its axial and torsional stiffness are compared and discussed. The results show that both the lay angle of the steel wires and the interlayer friction coefficient have a significant influence on the axial and torsional stiffness of the pipe, whereas the damaged length of the outer sheath has virtually no effect.

In the energy harvesting field, it is critical to efficiently convert ambient vibrations into usable electrical energy, especially under conditions characterized by low amplitude and random excitations. This study introduces a novel hybrid bistable piezoelectric energy harvester (HBPEH) designed to optimize energy conversion in challenging environmental conditions. The HBPEH features a unique piezoelectric cantilever beam integrated with a dynamic amplifier at the fixed end, significantly enhancing both rotational and lateral displacements of the beam. This innovation lowers the threshold for snap-through events, crucial for maximizing energy transfer in bistable systems, and enables superior energy harvesting capabilities. Furthermore, the HBPEH demonstrates significantly higher power outputs when subjected to excitation intensities beyond critical levels, outperforming conventional energy harvesters. Extensive numerical and theoretical analyses confirm that the HBPEH offers a promising solution for applications hindered by suboptimal energy conversion rates. Its ability to operate effectively under diverse and unpredictable excitation conditions underscores the HBPEH's robustness and superiority in advanced energy harvesting scenarios. The design improvements introduced in this study highlight the potential of the HBPEH to transform energy harvesting approaches. By addressing the limitations of traditional harvesters, the HBPEH provides enhanced efficiency and reliability, making it suitable for a broader range of practical applications in variable environmental conditions.