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Abstract Purpose Total Hip Arthroplasty (THA) is the primary treatment for hip diseases today. Nevertheless, total hip arthroplasty has its challenges, and one of these challenges is the potential for incorrect execution of the preoperative planning process. Such errors can lead to complications such as loosening and instability of the prosthesis and leg length discrepancy. In this study, we used human phantoms to investigate the influence of pelvic and femoral factors on prosthesis size selection in the preoperative planning of total hip arthroplasty and to provide a reference standard for clinical imaging in preoperative planning of total hip arthroplasty. Methods In this experiment, we utilised a custom-made experimental device that enabled us to manipulate the movement of the pelvis and femur in various directions. The device also incorporated sensors to control the angle of movement. By obtaining X-rays from different positions and angles, we were able to determine the size of the prosthesis based on the 2D preoperative planning generated by the mediCAD software. Results When the pelvis was in a nonneutral position, the size of the acetabular cup varied within a range of three sizes. Similarly, when the femur was in a nonneutral position, the size of the femoral stem varied within a range of two sizes. The movement of the pelvis and femur in the coronal plane, relative to the neutral position, did not impact the selection of the prosthesis size. However, the motion of the pelvis and femur in the sagittal and transverse planes had a notable effect. Conclusion The selection of the prosthesis size for preoperative planning can be significantly influenced by specific positions of the pelvis and femur. It is crucial for the radiographer to ensure that the pelvis and femur maintain a standard neutral position, particularly in the sagittal and transverse planes, during the image acquisition process.

Abstract Background Drug-dependent insomnia refers to insomnia patients taking sedatives and sleeping pills regularly for a long period. Auricular acupressure (AA) has attracted growing attention as a complementary treatment for insomnia. Nevertheless, there is a lack of rigorous studies evaluating AA specifically for estazolam-dependent insomnia. Our proposed trial aims to assess the therapeutic effect of AA on estazolam-dependent insomnia. Methods This study is a randomized, single-blinded, three-arm controlled trial. No less than 108 participants will be randomized into one of three groups: AA group, sham auricular acupressure (SAA) group, and conventional dosage reduction group. All treatments will be administered for 4 weeks, with a follow-up period of 1 month. The primary clinical outcomes will be estazolam dosing and reduction rates, serum gamma-aminobutyric acid (GABA) and cortisol (CORT) levels. Secondary outcomes will concern the Pittsburgh sleep quality index (PSQI) and Benzodiazepine Withdrawal Symptom Questionnaire (BWSQ). Both intention-to-treat and per-protocol analyses will be performed, with the significance level determined as 5%. Discussion The study results will provide evidence on the efficacy and safety of AA in managing estazolam-dependent insomnia by analyzing its immediate effect, time-effect relationship, and reduction of estazolam use. Trial Registration Clinicaltrials.gov (identification number: NCT06258226; Registered 5 February 2024, https://clinicaltrials.gov/ct2/show/NCT06258226 ).

Abstract Calcaneal body fractures are often associated with varying degrees of shortening deformities. Restoring calcaneal length is crucial for the functional prognosis of the foot. Through finite element analysis, this study compared the biomechanical effects of multiple fixation schemes for calcaneal fractures. We delineated and assembled the finite element model of the Sanders type II calcaneal fracture and four internal fixation simulations (namely distraction screw, lag screw, frame locking plate, and T-shaped locking plate). Different axial forces (350, 700, and 1400 N) were then applied to simulate various postures. We then compared the inner and outer shortening distances (D1 and D2, respectively), equivalent von Mises stress, and maximum von Mises stress of the calcaneus. In the individual model, with an increase in the pressure, D1, D2, and the maximum von Mises stress gradually increased. At 1400 N, D1 and D2 for the internal fixation schemes were as follows: distraction screw (0.03 mm, 0.1 mm)

Abstract Background Liver metastasis is one of the primary causes of poor prognosis in colon adenocarcinoma (COAD) patients, but there are few studies on its biomarkers. Methods The Cancer Genome Atlas (TCGA)-COAD, GSE41258, and GSE49355 datasets were acquired from the public database. Differentially expressed genes (DEGs) between liver metastasis and primary tumor samples in COAD were identified by limma, and functional enrichment analysis were performed. MuTect2 and maftools were used to measure somatic mutation rates, while ADTEx was used to measure copy number variations (CNVs). The intersection of three machine learning methods, support vector machine (SVM), Random Forest, and least absolute shrinkage and selection operator (LASSO), is utilized to screen biomarkers, and their diagnostic performance is subsequently validated. The correlation between biomarkers and immune cells infiltration was analyzed by Spearman method. Results 47 DEGs between liver metastasis and primary tumor samples in COAD were obtained, which were mainly enriched in the complement and coagulation, extracellular matrix (ECM), and peptidase regulator activity, etc. 38 out of 47 DEGs had mutations and exhibited a high frequency of CNV amplification or deletion. Furthermore, 3 biomarkers (MMP3, MAB21L2, and COLEC11) were screened, which showed good diagnostic performance. The proportion of multiple immune cells, such as B cells naive, T cells CD4 naive, Monocytes, and Dendritic cells resting, was higher in liver metastasis samples than that in primary tumor samples. Meanwhile, MMP3, MAB21L2, and COLEC11 exhibited an outstanding correlation with immune cells infiltration. Conclusion In short, 3 biomarkers with good diagnostic efficacy were identified, providing a new perspective of therapeutic targets for liver metastasis in COAD.

Abstract This paper proposes an adaptive saturation module to enhance the transient stability of grid‐following inverters after voltage‐dip inception and fault‐clearance moment. The equal‐area criterion reveals that a large acceleration area will be obtained due to the step change of current reference according to grid codes, which may lead to the loss of synchronism with the grid. It is found that the saturation module used with the phase‐locked loop can enhance the transient stability performance by reducing the acceleration area. To simultaneously adapt to the two cases (the inception and clearance of the voltage‐dip fault), an adaptive saturation module that can automatically adjust the clamping mode is proposed, which is the main contribution of the paper. The selection of the threshold value for the saturation module is also presented. A comprehensive comparison is made between the proposed solution and state‐of‐art solutions. Finally, the effectiveness of the proposed control strategy is confirmed by the experimental tests.

This article examines the relationship between patent foramen ovale (PFO) and migraine, emphasizing the mechanisms underlying the connection and the historical status of transcatheter PFO closure as a treatment for migraine. Patent foramen ovale is the most prevalent congenital cardiac defect in adults and frequently co-occurs with migraine, particularly migraine with aura. This article reviews several studies that have identified a significant prevalence of PFO in patients with migraine, implying that PFO and migraine may be more closely associated than previously thought. The underlying mechanisms of this association involve the transfer of emboli from the venous system to systemic circulation through the PFO, which can result in a range of clinical conditions. Transcatheter PFO closure therapy has demonstrated benefits in some patients with migraine; however, additional research is required to determine its effectiveness and safety. This article offers a comprehensive review of the current understanding of the link between PFO and migraine and emphasizes the need for further research in this field.

Abstract Novel neoadjuvant immunotherapy combined with chemotherapy (neoICT) has improved outcomes for patients with esophageal squamous-cell carcinoma (ESCC), but challenges persist in low response rates and therapy resistance. Little is known about the intra-tumoral heterogeneity in the ESCC tumor microenvironment (TME) that underlies differential responses to neoadjuvant therapy. We applied single-cell RNA sequencing (scRNA-seq) profiling and multiplexed immunofluorescence staining to thoroughly decipher the TME in ESCC specimens from a neoadjuvant anti-PD1 combination therapy clinical trial. The cancer-associated fibroblasts (CAFs) population showed the significant alteration in abundance following neoadjuvant therapy. Specifically, IL6 + CCL2 + immunomodulatory CAFs and a novel CD248 + mechanoresponsive CAFs subset exhibited increasing infiltration. Mechanistically, CD248 + mechanoresponsive CAFs approached and lined the tumor nest to physically block the infiltration of CD8 + T cells and drug delivery, while IL6 + CCL2 + immunomodulatory CAFs induced therapeutic resistance with distinct IL-6 expression. Among patients treated with neoICT, we observed prominent CAF-T cell interactions. In particular, the NECTIN2-TIGIT ligand-receptor pair was enriched in treated samples, and TIGIT was identified as the major inhibitory checkpoint of T cells. Our findings demonstrate distinct alterations in TME constituent responses to neoadjuvant immunotherapy and identify functional phenotypes of CAFs associated with unfavorable therapeutic responses in patients. This provides potential targets to enhance responses to neoadjuvant therapy in ESCC.

Abstract Background Sepsis-induced cardiomyopathy (SICM) is a common and life-threatening complication of sepsis, significantly contributing to elevated mortality. This study aimed to identify crucial indicators for the prompt and early assessment of SICM. Methods Patients diagnosed with sepsis or SICM within 24 h of intensive care unit (ICU) admission were enrolled in this prospective observational study. Patients were assigned to the training set, validation set and external test set. The primary endpoint was 7-day ICU mortality, and the secondary endpoint was 28-day ICU mortality. Three machine learning algorithms were utilized to identify relevant indicators for diagnosing SICM, incorporating 64 indicators including serum biomarkers associated with cardiac, renal, and liver function, lipid metabolism, coagulation, and inflammation. Internal and external validations were performed on the screening results. Patients were then stratified based on the cut-off value of the most diagnostically effective biomarker identified, and their prognostic outcomes were observed and analyzed. Results A total of 270 patients were included in the training and validation set, and 52 patients were included in the external test set. Age, sex, and comorbidities did not significantly differ between the sepsis and SICM groups (P > 0.05). The support vector machine (SVM) algorithm identified six indicators with an accuracy of 84.5%, the random forest (RF) algorithm identified six indicators with an accuracy of 81.9%, and the logistic regression (LR) algorithm screened out seven indicators. Following rigorous selection, a diagnostic model for sepsis-induced cardiomyopathy was established based on heart-type fatty acid binding protein (H-FABP) (OR 1.308, 95% CI 1.170–1.462, P

Abstract Background Lymph node metastasis (LNM) is the primary mode of metastasis in gastric cancer (GC). However, the precise mechanisms underlying this process remain elusive. Tumor cells necessitate lipid metabolic reprogramming to facilitate metastasis, yet the role of lipoprotein lipase (LPL), a pivotal enzyme involved in exogenous lipid uptake, remains uncertain in tumor metastasis. Therefore, the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this process. Methods Intracellular lipid levels were quantified using oil red O staining, BODIPY 493/503 staining, and flow cytometry. Lipidomics analysis was employed to identify alterations in intracellular lipid composition following LPL knockdown. Protein expression levels were assessed through immunohistochemistry, Western blotting, and enzyme‐linked immunosorbent assays. The mouse popliteal LNM model was utilized to investigate differences in LNM. Immunoprecipitation and mass spectrometry were employed to examine protein associations. In vitro phosphorylation assays and Phos‐tag sodium dodecyl‐sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin‐like protein 4 (ANGPTL4) phosphorylation. Results We identified that an elevated intracellular lipid level represents a crucial characteristic of node‐positive (N+) GC and further demonstrated that a high‐fat diet can expedite LNM. LPL was found to be significantly overexpressed in N+ GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC cells. Leptin, an obesity‐related hormone, intercepted the effect exerted by ANGPTL4/Furin on LPL cleavage. Circulating leptin binding to the leptin receptor could induce the activation of inositol‐requiring enzyme‐1 (IRE1) kinase, leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with LPL. Moreover, our research revealed that LPL disrupted lipid homeostasis by elevating intracellular levels of arachidonic acid, which then triggered the cyclooxygenase‐2/prostaglandin E2 (PGE2) pathway, thereby promoting tumor lymphangiogenesis. Conclusions Leptin‐induced phosphorylation of ANGPTL4 facilitates LPL‐mediated lipid uptake and consequently stimulates the production of PGE2, ultimately facilitating LNM in GC.

Abstract Cerium oxide (CeO2) nanospheres have limited enzymatic activity that hinders further application in catalytic therapy, but they have an “oxidation switch” to enhance their catalytic activity by increasing oxygen vacancies. In this study, according to the defect-engineering strategy, we developed PtCuOX/CeO2-X nanozymes as highly efficient SOD/CAT mimics by introducing bimetallic copper (Cu) and platinum (Pt) into CeO2 nanospheres to enhance the oxygen vacancies, in an attempt to combine near-infrared (NIR) irradiation to regulate microenvironment for osteoarthritis (OA) therapy. As expected, the Cu and Pt increased the Ce3+/Ce4+ ratio of CeO2 to significantly enhance the oxygen vacancies, and simultaneously CeO2 (111) facilitated the uniform dispersion of Cu and Pt. The strong metal-carrier interaction synergy endowed the PtCuOX/CeO2-X nanozymes with highly efficient SOD/CAT-like activity by the decreased formation energy of oxygen vacancy, promoted electron transfer, the increased adsorption energy of intermediates, and the decreased reaction activation energy. Besides, the nanozymes have excellent photothermal conversion efficiency (55.41%). Further, the PtCuOX/CeO2-X antioxidant system effectively scavenged intracellular ROS and RNS, protected mitochondrial function, and inhibited the inflammatory factors, thus reducing chondrocyte apoptosis. In vivo, experiments demonstrated the biosafety of PtCuOX/CeO2-X and its potent effect on OA suppression. In particular, NIR radiation further enhanced the effects. Mechanistically, PtCuOX/CeO2-X nanozymes reduced ras-related C3 botulinum toxin substrate 1 (Rac-1) and p-p65 protein expression, as well as ROS levels to remodel the inflammatory microenvironment by inhibiting the ROS/Rac-1/nuclear factor kappa-B (NF-κB) signaling pathway. This study introduces new clinical concepts and perspectives that can be applied to inflammatory diseases. Graphical Abstract

Abstract Background Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. Methods A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. Results This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p

Abstract Considering the superior luminous intensity characteristics of lasers, a thermal simulation platform employing laser-induced heating in an aerobic environment was developed. Achieving a uniformly distributed flat-topped square laser beam output was facilitated through optical fibre bundling techniques, while precise control over laser power output was attained through current modulation. Utilising the aforementioned system, thermal shock simulation experiments were conducted in an aerobic environment, subjecting two types of high-temperature-resistant composites, namely C/C and C/SiC, to temperatures up to 1800 °C. These composites were lightweight, heat-resistant materials designed for hypersonic vehicle applications. The results show that the system and method can be used to simulate high temperatures, rapid temperature increases, and thermal shocks on C/C composite materials, with minimal variation in the coupling coefficient under aerobic conditions. The system and method can also provide key technology support for thermal-force-oxygen coupling testing of high temperature resistant materials.

Abstract Heterogeneous and monolithic integration of the versatile low-loss silicon nitride platform with low-temperature materials such as silicon electronics and photonics, III–V compound semiconductors, lithium niobate, organics, and glasses has been inhibited by the need for high-temperature annealing as well as the need for different process flows for thin and thick waveguides. New techniques are needed to maintain the state-of-the-art losses, nonlinear properties, and CMOS-compatible processes while enabling this next generation of 3D silicon nitride integration. We report a significant advance in silicon nitride integrated photonics, demonstrating the lowest losses to date for an anneal-free process at a maximum temperature 250 °C, with the same deuterated silane based fabrication flow, for nitride and oxide, for an order of magnitude range in nitride thickness without requiring stress mitigation or polishing. We report record low anneal-free losses for both nitride core and oxide cladding, enabling 1.77 dB m-1 loss and 14.9 million Q for 80 nm nitride core waveguides, more than half an order magnitude lower loss than previously reported sub 300 °C process. For 800 nm-thick nitride, we achieve as good as 8.66 dB m−1 loss and 4.03 million Q, the highest reported Q for a low temperature processed resonator with equivalent device area, with a median of loss and Q of 13.9 dB m−1 and 2.59 million each respectively. We demonstrate laser stabilization with over 4 orders of magnitude frequency noise reduction using a thin nitride reference cavity, and using a thick nitride micro-resonator we demonstrate OPO, over two octave supercontinuum generation, and four-wave mixing and parametric gain with the lowest reported optical parametric oscillation threshold per unit resonator length. These results represent a significant step towards a uniform ultra-low loss silicon nitride homogeneous and heterogeneous platform for both thin and thick waveguides capable of linear and nonlinear photonic circuits and integration with low-temperature materials and processes.

Abstract Nanoplasmas induced by intense laser fields have attracted enormous attention due to their accompanied spectacular physical phenomena which are vigorously expected by the community of science and industry. For instance, the energetic electrons and ions produced in laser-driven nanoplasmas are significant for the development of compact beam sources. Nevertheless, effective confinement on the propagating charged particles, which was realized through magnetic field modulation and target structure design in big facilities, are largely absent in the microscopic regime. Here we introduce a reliable scheme to provide control on the emission direction of protons generated from surface ionization in gold nanoparticles driven by intense femtosecond laser fields. The ionization level of the nanosystem provides us a knob to manipulate the characteristics of the collective proton emission. The most probable emission direction can be precisely steered by tuning the excitation strength of the laser pulses. This work opens new avenue for controlling the ion emission in nanoplasmas and can vigorously promote the fields such as development of on-chip beam sources at micro-/nano-scales.

In recent years, bridge safety accidents caused by insufficient shear bearing capacity of bridges have attracted increasing attention. The main causes include internal factors such as insufficient bridge section and deterioration of steel bars, as well as external factors, for example, vehicle load surge and improper maintenance. To address this issue to some degree, this article adopts the method of strengthening RC beams with ultra-high performance concrete (UHPC) and conducts parameter analysis using finite element method, taking into consideration the influence of four parameters: reinforcement material, reinforcement thickness, reinforcement length, and reinforcement form on the shear strengthening characteristics of RC rectangular beams. After obtaining the optimal reinforcement plan through parameter analysis, the author applied the research results to an existing bridge with insufficient shear strength. It then turned out that the shear bearing capacity of the reinforced bridge’s inclined section increased by approximately 27.1%. Simple and fast in construction, this reinforcement method is one of the methods that is effective to increase cross-section reinforcement; besides, it features good economic characteristics and applicability.

Path planning is one of the key elements for achieving rapid and stable flight when unmanned aerial vehicles (UAVs) are conducting monitoring and inspection tasks at ultra-low altitudes or in orchard environments. It involves finding the optimal and safe route between a given starting point and a target point. Achieving rapid and stable flight in complex environments is paramount. In environments characterized by high-density obstacles, the stability of UAVs remains a focal point in the research of path planning algorithms. This study, utilizing a feature attention mechanism, systematically identifies distinctive points on the obstacles, leading to the development of the RFA-Star (R5DOS Feature Attention A-star) path planning algorithm. In MATLAB, random maps were generated to assess the performance of the RFA-Star algorithm. The analysis focused on evaluating the effectiveness of the RFA-Star algorithm under varying obstacle density conditions and different map sizes. Additionally, comparative analyses juxtaposed the performance of the RFA-Star algorithm against three other algorithms. Experimental results indicate that the RFA-Star algorithm demonstrates the shortest computation time, approximately 84%-94% faster than the RJA-Star algorithm and 51%-96% faster than the Improved A-Star. The flight distance is comparable to the RJA-Star algorithm, with slightly more searched nodes. Considering these factors collectively, the RFA-Star algorithm exhibits a relatively superior balance between computational efficiency and path quality. It consistently demonstrates efficient and stable performance across diverse complex environments. However, for comprehensive performance enhancement, further optimization is necessary.

Abstract Neuroendocrine transdifferentiation (NEtD), also commonly referred to as lineage plasticity, emerges as an acquired resistance mechanism to molecular targeted therapies in multiple cancer types, predominately occurs in metastatic epidermal growth factor receptor (EGFR)‐mutant non‐small cell lung cancer treated with EGFR tyrosine kinase inhibitors and metastatic castration‐resistant prostate cancer treated with androgen receptor targeting therapies. NEtD tumors are the lethal cancer histologic subtype with unfavorable prognosis and limited treatment. A comprehensive understanding of molecular mechanism underlying targeted‐induced plasticity could greatly facilitate the development of novel therapies. In the past few years, increasingly elegant studies indicated that NEtD tumors share key the convergent genomic and phenotypic characteristics irrespective of their site of origin, but also embrace distinct change and function of molecular mechanisms. In this review, we provide a comprehensive overview of the current understanding of molecular mechanism in regulating the NEtD, including genetic alterations, DNA methylation, histone modifications, dysregulated noncoding RNA, lineage‐specific transcription factors regulation, and other proteomic alterations. We also provide the current management of targeted therapies in clinical and preclinical practice.

Abstract Background The blood–cerebrospinal fluid barrier (BCSFB) comprises the choroid plexus epithelia. It is important for brain development, maintenance, function, and especially for maintaining immune homeostasis in the cerebrospinal fluid (CSF). Although previous studies have shown that the peripheral immune function of the body is impaired upon exposure to microgravity, no studies have reported changes in immune cells and cytokines in the CSF that reflect neuroimmune status. The purpose of this study is to investigate the alterations in cerebrospinal fluid (CSF) immune homeostasis induced by microgravity and its mechanisms. This research is expected to provide basic data for brain protection of astronauts during spaceflight. Methods The proportions of immune cells in the CSF and peripheral blood (PB) of SMG rats were analyzed using flow cytometry. Immune function was evaluated by measuring cytokine concentrations using the Luminex method. The histomorphology and ultrastructure of the choroid plexus epithelia were determined. The concentrations of intercellular junction proteins in choroid plexus epithelial cells, including vascular endothelial‐cadherin (VE‐cadherin), zonula occludens 1 (ZO‐1), Claudin‐1 and occludin, were detected using western blotting and immunofluorescence staining to characterize BCSFB injury. Results We found that SMG caused significant changes in the proportion of CD4 and CD8 T cells in the CSF and a significant increase in the levels of cytokines (GRO/KC, IL‐18, MCP‐1, and RANTES). In the PB, there was a significant decrease in the proportion of T cells and NKT cells and a significant increase in cytokine levels (GRO/KC, IL‐18, MCP‐1, and TNF‐α). Additionally, we observed that the trends in immune markers in the PB and CSF were synchronized within specific SMG durations, suggesting that longer SMG periods (≥21 days) have a more pronounced impact on immune markers. Furthermore, 21d‐SMG resulted in ultrastructural disruption and downregulated expression of intercellular junction proteins in rat choroid plexus epithelial cells. Conclusions We found that SMG disrupts the BCSFB and affects the CSF immune homeostasis. This study provides new insights into the health protection of astronauts during spaceflight.

Cancer is a significant and constantly growing clinical problem all over the word. For many types of cancer there has been little change in mortality rate of CRC in the past decades and treatment options are limited. A striking example is malignant Glioblastoma (GBM) which exhibits a high degree of infiltration of surrounding healthy brain tissue, extremely high mortality rate, morbidity and most life-years lost of any cancer. Considerable research efforts in the last several decades have failed to improve these outcomes. Boron Capture Neutron Therapy (BNCT) is an experimental radiotherapy (RT) that shows the best hope for the patients for whom all current therapies fail. BNCT involves the intracellular release of alpha and Li-ion particles from boron in response to neutron beam and therefore its success is critically dependent on achieving high intracellular concentrations of boron atoms within the cancerous cells. Boron phenylalanine (BPA) is the most used compound to deliver boron atoms, but achieving high intracellular concentration of BPA is difficult with this small molecule compound and is an absolute limiting factor for the better outcome of BNCT. Our approach focused on a delivery of a high and stable concentration of boron atoms in a form of novel trimetallic core-shell nanoparticles, combining boron for BNCT and iron for magnetic targeting in the core, and a gold shell for stability and attachment of targeting therapeutic peptides. The research was targeted towards comparing different synthesis variables to form these core-shell particles and incorporate as much boron into the core as possible via redox-transmetalation. Partial gold shells were formed around the core via island growth with a molar ratio of Fe/B of 0.64 and high incorporation of boron.

Female reproductive timing and lifespan, with a close relation to long-term health outcomes, have been altered in U.S. women over the past decades. However, epidemiologic evidence of the potential causes was lacking. On the basis of 1981 naturally postmenopausal women from the National Health and Nutrition Examination Survey 1999–2020, this study aimed to investigate the associations of urinary heavy metals with age at menarche, age at menopause, and reproductive lifespan. Multivariate generalized linear regression and addictive models were used for single metal exposure analysis, and weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) models were employed for mixed exposures. In the fully adjusted model, higher urinary antimony concentration was associated with earlier age at menarche of 0.137 years, while higher concentrations of cadmium, cesium, lead, antimony, and thallium were associated with delayed age at menopause of 0.396–0.687 years. Additionally, urinary barium, cesium, lead, antimony, and thallium levels were associated with longer reproductive lifespan ranging between 0.277 and 0.713 years. Both WQS and BKMR models showed significantly positive associations of metal mixtures with age at menopause (β: 0.667, 95 % CI: 0.120–1.213) and reproductive lifespan (β: 0.686, 95 % CI: 0.092–1.280), with cadmium and lead identified as principal contributors. In conclusion, heavy metal exposures were associated with reproductive timing and lifespan of U.S. women, highlighting the need for further prevention and intervention strategies.

Efforts to enhance the performance of thermoelectric generators (TEGs) in engine waste heat recovery have primarily focused on directly increasing energy conversion efficiency. Heat leakage can occur in many parts of a TEG. It is needed to develop a model to help researchers study this phenomenon and propose measures to reduce heat leakage. To address this gap, this study establishes and validates a computational fluid dynamic (CFD) and finite element (FE) coupled model based on a TEG prototype and its engine test bench. Unlike other models, this approach captures the intricate dynamics of heat propagation from the TEG via air gaps, encompassing conduction, convection, and radiation. Comprehensive analysis reveals that heat leakage accounts for approximately 11% of TEG power output loss. Ignoring the impact of heat leakage can lead to an overestimation of TEG power output. Key areas of heat leakage are identified, and numerical factors influencing this phenomenon are explored. Vertical TEG placement and optimal spacing between thermoelectric modules emerge as effective strategies for mitigating the impact of heat leakage on power output. Leveraging these insights, strategic thermoelectric module placement, vertical TEG orientation, and the application of thermal insulation materials to the heat exchanger are proposed as measures to enhance TEG power output by approximately 5%. The experimental and numerical results underscore the feasibility of optimizing TEGs from the perspective of heat leakage, a crucial aspect previously overlooked. These findings provide valuable insights for future TEG optimization endeavors, highlighting the importance of addressing heat leakage to maximize TEG performance.

Background Stage IV gastric cancer is a highly heterogeneous and lethal tumor with few therapeutic strategies. The combination of programmed cell death protein 1 inhibitors and chemotherapy is currently the standard frontline treatment regimen for advanced gastric cancer. Nevertheless, it remains a great challenge to screen the beneficiaries of immunochemotherapy and expand indications for this treatment regimen.Methods We conducted a pathological assessment to ascertain the importance of tertiary lymphoid structures based on the tissue samples collected from patients with stage IV gastric cancer (n=15) both prior to and following immunochemotherapy treatment. Additionally, we used spatial (n=10) and single-cell transcriptional analysis (n=97) to investigate the key regulators of tertiary lymphoid structures (TLSs). Multiplex immunofluorescence and image analysis (n=34) were performed to explore the association between tumor-infiltrating CXCL13+ CD160+ CD8+ T cells and TLSs. The relationship between CXCL13+ CD160+ CD8+ T cells and the responsiveness to immunotherapy was also evaluated by multiplex immunofluorescence and image analysis approaches (n=15). Furthermore, we explored the intrinsic characteristics of CXCL13+ CD160+ CD8+ T cells through various experimental techniques, including quantitative reverse transcription-PCR, western blot, and flow cytometry.Results We found that responders exhibited higher levels of TLSs and CXCL13+ CD160+ CD8+ T cells in biopsy tissues prior to immunochemotherapy compared with non-responders. Following conversion therapy, responders also had a higher percentage of mature TLSs and a higher number of CXCL13+ CD160+ CD8+ T cells in surgical resections. Moreover, we discovered that vitamin B6 in CD160+ CD8+ T cells could reduce the ubiquitination modification of HIF-1α by MDM2, thereby attenuating the degradation of HIF-1α. Consequently, this led to the transcriptional upregulation of CXCL13 expression, facilitating the recruitment of CXCR5+ B cells and the formation of TLSs.Conclusion The number and maturity of TLSs, along with the extent of CXCL13+ CD160+ CD8+ T-cell infiltration, might function as potential indicators for assessing the effectiveness of immunotherapy in treating gastric malignancies. Furthermore, our research suggests that vitamin B6 could enhance the secretion of CXCL13 by CD160+ CD8+ T cells by reducing the degradation of HIF-1α. Additionally, we demonstrate that vitamin B6 supplementation or targeting pyridoxal kinase could substantially improve the efficacy of immunotherapies for gastric cancer.

Abstract Background Autoimmune uveitis is an inflammatory disease triggered by an aberrant immune response. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) are emerging as potential therapeutic agents for this condition. CD73, an ectoenzyme present on MSC-sEVs, is involved in mitigating inflammation by converting extracellular adenosine monophosphate into adenosine. We hypothesize that the inhibitory effect of MSC-sEVs on experimental autoimmune uveitis (EAU) could be partially attributed to the surface expression of CD73. Methods To investigate novel therapeutic approaches for autoimmune uveitis, we performed lentiviral transduction to overexpress CD73 on the surface of MSC-sEVs, yielding CD73-enriched MSC-sEVs (sEVs-CD73). Mice with interphotoreceptor retinoid-binding protein (IRBP)-induced EAU were grouped randomly and treated with 50 µg MSC-sEVs, vector infected MSC-sEVs, sEVs-CD73 or PBS via single tail vein injection. We evaluated the clinical and histological features of the induced mice and analyzed the proportion and functional capabilities of T helper cells. Furthermore, T-cells were co-cultured with various MSC-sEVs in vitro, and we quantified the resulting inflammatory response to assess the potential therapeutic benefits of sEVs-CD73. Results Compared to MSC-sEVs, sEVs-CD73 significantly alleviates EAU, leading to reduced inflammation and diminished tissue damage. Treatment with sEVs-CD73 results in a decreased proportion of Th1 cells in the spleen, draining lymph nodes, and eyes, accompanied by an increased proportion of regulatory T-cells (Treg cells). In vitro assays further reveal that sEVs-CD73 inhibits T-cell proliferation, suppresses Th1 cells differentiation, and enhances Treg cells proportion. Conclusion Over-expression of CD73 on MSC-sEVs enhances their immunosuppressive effects in EAU, indicating that sEVs-CD73 has the potential as an efficient immunotherapeutic agent for autoimmune uveitis.

Abstract The escalation of cloud services, driven by their accessibility, improved performance, and cost-effectiveness, has led cloud service providers to consistently seek methods to expedite job completion, thereby boosting profits and reducing energy consumption expenses. Despite developing numerous scheduling algorithms, many of these techniques address only a specific objective within the scheduling process. To efficiently achieve better optimization results for the cloud task scheduling problem, a novel approach, the Enhanced Whale Optimization Algorithm (EWOA), is proposed. EWOA integrates the WOA with the Lévy flight. The incorporation of Lévy flight is tailored to broaden the search space of WOA, expediting convergence with adaptive crossover. The EWOA model is simulated using the Cloudsim tool and evaluated under diverse test conditions. The effectiveness of EWOA is assessed by employing various parameters and comparing them with existing algorithms. The results demonstrate that EWOA outperforms other algorithms in resource utilization, energy consumption, and execution cost, establishing its superiority in addressing the complexities of multi-objective cloud task scheduling.

Abstract Bacteriophage infection, a pivotal process in microbiology, initiates with the phage’s tail recognizing and binding to the bacterial cell surface, which then mediates the injection of viral DNA. Although comprehensive studies on the interaction between bacteriophage lambda and its outer membrane receptor, LamB, have provided rich information about the system’s biochemical properties, the precise molecular mechanism remains undetermined. This study revealed the high-resolution cryo-electron microscopy (cryo-EM) structures of the bacteriophage lambda tail complexed with its irreversible Shigella sonnei 3070 LamB receptor and the closed central tail fiber. These structures reveal the complex processes that trigger infection and demonstrate a substantial conformational change in the phage lambda tail tip upon LamB binding. Providing detailed structures of bacteriophage lambda infection initiation, this study contributes to the expanding knowledge of lambda-bacterial interaction, which holds significance in the fields of microbiology and therapeutic development.

This is an article in the field of ceramics and composites. Phosphogypsum has a large discharge and low utilization rate,and resource utilization is imminent. The heat treatment of phosphogypsum under different temperatures was studied. The influence of heat treatment temperature on the physical phase and microstructure of phosphogypsum, and the compressive strength, phase and microstructure of non burningsample of building materials by the treated phosphogypsum were studied. The results show that with the increase of heat treatment temperature, the crystallinity of gypsum increases and the crystal form changes. After heat treatment at 80 ℃, the crystal of gypsum is dense, and part of it is converted into hemihydrate gypsum. The Gypsum dihydrate formed by hydration recrystallization of hemihydrate gypsum fills the void, forming the internal microstructure of dense and mutual bonding of crystals, so the compressive strength of no burning building materials is greatly improved. After curing for 7 days and 28 days, the compressive strength of non burningsample (the mass ratio of phosphogypsum to cement is 4∶1) reaches 36.45 MPa and 38.12 MPa. The compressive strength of the sample soaked in water for 24 hours is still 21.03 MPa.

Abstract Yangmingism, a crucial component of Chinese Confucianism, has profoundly impacted the development of Eastern civilization throughout history and gained new significance within modern contexts. This study employs social network and GIS spatial analyses to investigate the spatio-temporal evolution and patterns of Yangmingism during the Ming and Qing dynasties. Conclusions drawn include: (1) Yangmingism spread during the Ming and Qing dynasties followed five phases (rise-peak-decline-revival-trough), consistent with general cultural diffusion processes. (2) The spatial structure of regions accepting Yangmingism changed from polycentric to localized ribbon-polycentric, then to monocentric, polycentric, and ultimately, fragmented distribution. Diffusion began with a point-axis structure along traffic routes, transitioned to a core-periphery spatial structure, and returned to a point-axis structure due to reduced diffusion potential energy. (3) Yangmingism diffusion exhibited distance decay characteristics, with the most extensive diffusion in the Han cultural region, primarily located within the middle and lower reaches of the Ganjiang River basin and the Yangtze River Delta. (4) Yangmingism diffusion reflected influences from local administrative hierarchies and cultural development. During the rise-to-peak phase, Yangmingism reached areas with higher administrative and cultural levels, while during the peak-to-decline phase, it disseminated from higher to lower hierarchy regions. (5) The spatial diffusion of Yangmingism is mainly relocation diffusion, followed by expansion diffusion. In the process of relocation diffusion, Yangmingism may reverse the diffusion from the “target regions” to the “source regions” due to the influence of the radiation of the high-ranking regions and the cultural innovation of the “target regions”.

Abstract Brain metastasis (BM) is one of the leading causes of cancer-related deaths in patients with advanced non-small cell lung cancer (NSCLC). However, limited treatments are available due to the presence of the blood-brain barrier (BBB). Upregulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in NSCLC has been found to promote BM. Conversely, downregulating LPCAT1 significantly suppresses the proliferation and metastasis of lung cancer cells. In this study, we firstly confirmed significant upregulation of LPCAT1 in BM sites compared to primary lung cancer by analyzing scRNA dataset. We then designed a delivery system based on a single-chain variable fragment (scFv) targeting the epidermal growth factor receptor (EGFR) and exosomes derived from HEK293T cells to enhance cell-targeting capabilities and increase permeability. Next, we loaded LPCAT1 siRNA (siLPCAT1) into these engineered exosomes (exoscFv). This novel scFv-mounted exosome successfully crossed the BBB in an animal model and delivered siLPCAT1 to the BM site. Silencing LPCAT1 efficiently arrested tumor growth and inhibited malignant progression of BM in vivo without detectable toxicity. Overall, we provided a potential platform based on exosomes for RNA interference (RNAi) therapy in lung cancer BM.

The on-ramp merging in multi-lane highway scenarios presents challenges due to the complexity of coordinating vehicles’ merging and lane-changing behaviors, while ensuring safety and optimizing traffic flow. However, there are few studies that have addressed the merging problem of ramp vehicles and the cooperative lane-change problem of mainline vehicles within a unified framework and proposed corresponding optimization strategies. To tackle this issue, this study adopts a cyber-physical integration perspective and proposes a graph-based solution approach. First, the information of vehicle groups in the physical plane is mapped to the cyber plane, and a dynamic conflict graph is introduced in the cyber space to describe the conflict relationships among vehicle groups. Subsequently, graph decomposition and search strategies are employed to obtain the optimal solution, including the set of mainline vehicles changing lanes, passing sequences for each route, and corresponding trajectories. Finally, the proposed dynamic conflict graph-based algorithm is validated through simulations in continuous traffic with various densities, and its performance is compared with the default algorithm in SUMO. The results demonstrate the effectiveness of the proposed approach in improving vehicle safety and traffic efficiency, particularly in high traffic density scenarios, providing valuable insights for future research in multi-lane merging strategies.

Due to the increase in traffic volume, load level, and service life of existing bridges, the bending bearing capacity of reinforced concrete beams (hereinafter referred to as RC beams) has decreased, leading to safety issues. In order to solve the problem of insufficient flexural bearing capacity of RC beams, this article adopts the method of ultra-high performance concrete (UHPC) flexural strengthening RC beams, establishes a finite element model of UHPC-RC reinforcement system, and conducts stress analysis with reinforcement thickness, reinforcement range, reinforcement form, and reinforcement height as parameters to determine the optimal scheme of the reinforcement system. Based on the calculation results, a theoretical formula for the maximum principal stress and maximum deflection of the reinforcement system is proposed. To verify the feasibility of the plan, a reinforcement design was carried out on an existing beam, and it was found that the bending bearing capacity of the RC beam increased by 21%; the high tensile strength of UHPC and the addition of steel fibers have a good limiting effect on cracks; The steel plate of the reinforcement system can be used as a template, reducing construction costs and having good economy.

Abstract Our study aimed to evaluate the correlation between levels of 2,4-DCP(2,4-Dichlorophenol) and 2,5-DCP(2,5-Dichlorophenol) and the prevalence of kidney stones in US female adults. Participants were chosen from the National Health and Nutrition Examination Survey database, spanning the years 2007–2016. Dose–response curves were analyzed using logistic regression, subgroup analyses, and other statistical methods to evaluate the relationship between 2,4-DCP and 2,5-DCP levels and the prevalence of kidney stones. The final study included 3220 participants aged over 20 years, with 252 females reporting a history of kidney stones. After accounting for all interfering variables, we found that every 0.1 ug/ml increase in 2.4-DCP correlated with a 1% rise in kidney stone prevalence (OR = 1.01, 95% CI 1.00, 1.01), whereas the same increase in 2.5-DCP was linked to a 27% growth in prevalence (OR = 1.27, 95% CI 1.01, 1.61). Sensitivity analysis was performed by triangulating 2,4-DCP and 2,5-DCP levels. The dose–response curves demonstrated a linear positive relationship between 2,4-DCP and 2,5-DCP levels and the risk of stone development. Our findings indicate a positive correlation between 2,4-DCP and 2,5-DCP levels and the prevalence of kidney stones in US female adults. This association is of clinical significance; however, a direct causal relationship cannot be definitively established.

Abstract Based on the advantages of laser high brightness, a high-temperature mechanical property measuring device has been developed, which can measure the high-temperature strength of C/SiC composites under the condition of short-term high-temperature rise rate and solve the problem of over-oxidation of materials in conventional high-temperature mechanical properties experiments. The experimental results show that the maximum temperature rise rate is 260 ℃/s at the initial heating stage, and the test time is controlled within 35 s. The tensile strength of the prepared C/SiC composites decreased first and then increased at high temperatures and laser-induced high temperatures. The experimental results are similar to those in the literature under the inert atmosphere. Oxidation has less of an effect on the mechanical characteristics of materials under conditions of rapid temperature rise. The system can be used to test the mechanical properties of composite materials at high temperatures and as a simulation platform for the thermal response of specific thermal protection systems subjected to a constant heat flux. This study can provide a new idea for testing ultra-high temperature mechanical properties of C/SiC materials and provide key technical support for the engineering application and high-temperature testing of C/SiC materials in high-temperature environments.

Highlights The innovation of this work mainly lies in the auto-regulation of reactive oxygen species (ROS) balance effective by combination of ROS antibacterial and ROS scavenging anti-inflammatory functions with a core–shell nanoplatform (CeO2@ZIF-8/Au), which can not only achieve high antibacterial efficiency, but also promote wound healing, and provide a new idea for the nano-catalytic system in the field of wound healing of bacterial infection.

This study employed the effect of sub-critical annealing heat treatment on the microstructure and anisotropy of the hybrid additive manufactured TC11 alloy. The results demonstrate that after sub-critical annealing, a gradient microstructure with the gradual changes in the morphology and content of primary α phases from the laser deposition zone to the substrate zone was formed. Moreover, the tensile anisotropy of the hybrid manufactured specimens was substantially reduced. In particular, when loading along to the deposition direction, the ultimate tensile strength of the heat-treated hybrid manufactured specimen was 1062 MPa, increased by 8.5%. And when loading perpendicular to the deposition direction, the elongation can reach 13.0%, increased by 86% compare to the as-deposited sample. These findings would also shed new insights for the modification of graded structural parts prepared by the hybrid manufacturing technique, laser additive repair and other methods.

BackgroundAtherosclerotic plaque rupture is a major cause of heart attack. Previous studies have shown that immune cells are involved in the development of atherosclerosis, but different immune cells play different roles. The aim of this study was to investigate the causal relationship between immunological traits and myocardial infarction (MI).MethodsTo assess the causal association of immunological profiles with myocardial infarction based on publicly available genome-wide studies, we used a two-sample mendelian randomization (MR) approach with inverse variance weighted (IVW) as the main analytical method. Sensitivity analyses were used to assess heterogeneity and horizontal pleiotropy.ResultsA two-sample MR analysis was conducted using IVW as the primary method. At a significance level of 0.001, we identified 47 immunophenotypes that have a significant causal relationship with MI. Seven of these were present in B cells, five in cDC, four in T cells at the maturation stage, six in monocytes, five in myeloid cells, 12 in TBNK cells, and eight in Treg cells. Sensitivity analyses were performed to confirm the robustness of the MR results.ConclusionsOur results provide strong evidence that multiple immune cells have a causal effect on the risk of myocardial infarction. This discovery provides a new avenue for the development of therapeutic treatments for myocardial infarction and a new target for drug development.

BackgroundAutoimmune encephalitis (AIE) encompasses a spectrum of rare autoimmune-mediated neurological disorders, which are characterized by brain inflammation and dysfunction. Autoantibodies targeting the N-methyl-d-aspartic acid receptor (NMDAR) and leucine-rich glioma-inactivated 1 (LGI1) are the most common subtypes of antibody-positive AIE. Currently, there are no approved therapies for AIE. Interleukin-6 (IL-6) signaling plays a role in the pathophysiology of AIE. Satralizumab, a humanized, monoclonal recycling antibody that specifically targets the IL-6 receptor and inhibits IL-6 signaling, has demonstrated efficacy and safety in another autoantibody-mediated neuroinflammatory disease, aquaporin-4 immunoglobulin G antibody-positive neuromyelitis optica spectrum disorder, and has the potential to be an evidence-based disease modifying treatment in AIE.ObjectivesCIELO will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of satralizumab compared with placebo in patients with NMDAR-immunoglobulin G antibody-positive (IgG+) or LGI1-IgG+ AIE.Study designCIELO (NCT05503264) is a prospective, Phase 3, randomized, double-blind, multicenter, basket study that will enroll approximately 152 participants with NMDAR-IgG+ or LGI1-IgG+ AIE. Prior to enrollment, participants will have received acute first-line therapy. Part 1 of the study will consist of a 52-week primary treatment period, where participants will receive subcutaneous placebo or satralizumab at Weeks 0, 2, 4, and every 4 weeks thereafter. Participants may continue to receive background immunosuppressive therapy, symptomatic treatment, and rescue therapy throughout the study. Following Part 1, participants can enter an optional extension period (Part 2) to continue the randomized, double-blind study drug, start open-label satralizumab, or stop study treatment and continue with follow-up assessments.EndpointsThe primary efficacy endpoint is the proportion of participants with a ≥1-point improvement in the modified Rankin Scale (mRS) score from study baseline and no use of rescue therapy at Week 24. Secondary efficacy assessments include mRS, Clinical Assessment Scale of Autoimmune Encephalitis (CASE), time to rescue therapy, sustained seizure cessation and no rescue therapy, Montreal Cognitive Assessment, and Rey Auditory Verbal Learning Test (RAVLT) measures. Safety, pharmacokinetics, pharmacodynamics, exploratory efficacy, and biomarker endpoints will be captured.ConclusionThe innovative basket study design of CIELO offers the opportunity to yield prospective, robust evidence, which may contribute to the development of evidence-based treatment recommendations for satralizumab in AIE.

Abstract Memristors are a candidate device for artificial neural systems due to their excellent conductance‐regulation ability and potential to simulate the characteristics of biological synapses. This study fabricated a Pt/TaOx/TiOy/Ti analog artificial synapse memristor that exhibits excellent multilevel storage property with a large on/off ratio of ≈660 times. The dynamic resistive switching mechanism is well expounded and validated by the reset stopping voltage dependent Schottky fitting results. Moreover, the essential biological synaptic characteristics such as long‐term potentiation/depression (LTP/D) and paired‐pulse facilitation (PPF) are successfully mimicked with a low pulse energy consumption of 12.69 nJ. A neuromorphic network constructed on the enhanced symmetry and linearity of conductance for this Pt/TaOx/TiOy/Ti memristive device can achieve 92.45% accuracy in recognizing handwritten pattern. These results demonstrate a significant potential for application Pt/TaOx/TiOy/Ti memristor in non‐volatile memory and bioinspired neuromorphic systems.

PurposeEpigenetic modifications play a crucial role in cancer development, and our study utilized public data to analyze which leads to the discovery of significant epigenetic abnormalities in lncRNAs, offering valuable insights into prognosis and treatment strategies for renal carcinoma.MethodsPublic data were obtained from the Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) database. The analysis of the online public data was all completed in R software.ResultsWe discovered a great number of epigenetic abnormalities of lncRNA in renal cancer, which is achieved by comparing the following modification and methylation of histone region changes on the promoter and enhancer of lncRNA: H3K27ac, H3K4me1, H3K4me3. As a result, 12 specific epigenetic disorders of lncRNA genes in renal cancer were identified. Finally, based on this lncRNA, we investigated the prognosis of renal cancer samples, among which 8 lncRNA can be seen as markers of prognosis in renal cancer, which had great prediction ability for ccRCC prognosis. Meanwhile, high risk score may pose response better to axitinib and nilotinib, but not sorafenib or sunitinib. Beyond, we observed an elevated level of risk score in immunotherapy non-responders. Further, biological enrichment and immuno-infiltration analysis was conducted to investigate the fundamental differences between patients categorized as high or low risk.ConclusionOur research improves the understanding in the function of epigenetic dysregulated long non-coding RNAs in renal carcinoma.

Primary familial brain calcification (PFBC), also known as Fahr’s disease, is a central nervous system calcium deposition disorder with symmetrical basal ganglia calcification. Most PFBC cases are caused by SLC20A2 gene variant. We report a Chinese female patient with PFBC and dopamine-responsive parkinsonism who had motor fluctuations and dyskinesia and recovered effectively after symptomatic medication adjustment. A novel heterozygous missense variant was found by whole-exome sequencing and proven harmful by family validation and genetic analysis. This example expands the phenotype of SLC20A2-associated PFBC patients and shows the clinical efficacy of dopaminergic replacement treatment.

Tinnitus, characterized by phantom sound perception, is a highly disruptive disorder lacking definitive and effective treatments. Its intricate neural mechanisms are not fully understood. Transcutaneous auricular vagus nerve stimulation (taVNS) has demonstrated potential as a substitute or supplementary treatment by activating central vagal pathways. However, standardized therapeutic protocols and objective tests to assess efficacy are lacking. Therefore, taVNS shows promise as a therapy for tinnitus, and treatment protocols should be optimized in future clinical trials.

In this paper, the influence of micro scale and nanoscale limestone powder (LP) on plastic viscosity of ultra-high performance concrete (UHPC) mixture was investigated. Moreover, a novel method for analyzing water film on particle surfaces has been presented based on low-field nuclear magnetic resonance technology (LF NMR). Results showed that approximately 95% of free water in UHPC slurry is adsorbed on the surface of particles, while the rest is filled in capillaries and macropores. Moreover, rheological properties of UHPC are related to particle size of limestone powder. Micro scale limestone powder (LP1) could reduce the heat release during early hydration of UHPC, increase the fluidity, but has no significant effect on the water film thickness. The plastic viscosity of UHPC mixed with 10% mass fraction of LP1 will decrease by 22.8%, the flowability will increase from 235 mm to 270 mm, and the compressive strength will remain unchanged at 160 MPa. However, nanoscale limestone powder (LP2) increases the heat release of UHPC and significantly reduces its fluidity. A 10% mass fraction of LP2 will reduce the water film thickness of the UHPC by 23.5%, increase the plastic viscosity by 38.5%, and reduce the flowability to 210 mm. Meanwhile, the compressive strength of UHPC will decrease if the mass fraction of LP2 exceeds 5%.

BackgroundResearch on the relationship between mild COVID-19 and the subsequent development of isolated optic neuritis (ON) with antibodies specific to myelin oligodendrocyte glycoprotein (MOG-ON) and aquaporin 4 (AQP4-ON) is limited, particularly case–control studies that directly compare these conditions within the same affected population.MethodsA retrospective analysis of initial MOG-ON and AQP4-ON cases during the COVID-19 peak and subsequent months. Patients were classified as possible COVID-19 related ON (PCRON) or non-COVID-19 related ON (NCRON). The study compared epidemiology, comorbidities, and clinical features between these groups.ResultsPatients with MOG-ON tended to develop ON symptoms closer in time to a mild COVID-19 infection compared to those with AQP4-ON (6.87 ± 6.25 weeks vs. 11.06 ± 5.84 weeks; p = 0.038), a significantly higher proportion of patients with MON-ON developing symptoms within 6 weeks after COVID-19 compared to those with AQP4-ON (15/23 [65.2%] vs. 5/17 [29.4%]; p = 0.025). Comparing MOG-ON and AQP4-ON patients, MOG-ON patients were more likely to have a recent infection before ON onset (73.1% vs. 30%; p = 0.007) and had better peak and post-treatment visual acuity (p = 0.01; p

Sustainable development is crucial for alleviating poverty among farmers. In this study, we examined the impact, and the mechanism underlying this impact, of the adoption of agricultural machinery services by farmers on their relative poverty from a multidimensional poverty perspective by employing the logit and ordered logit models and the Karlson–Holm–Breen (KHB) method. These results indicate that adopting agricultural machinery services can significantly reduce the probability of relative poverty among farmers, thereby expediting the sustainability of rural development. However, this poverty-reduction effect varies based on age and sex. The adoption of agricultural machinery services mainly reduces poverty by increasing farmers' human capital. Training in employment skills and non-agricultural work experience are the main transmission mechanisms. Therefore, the socialization of agricultural machinery services can be used as an effective policy tool to reduce relative poverty in developing countries, promote sustained improvements in farmers’ incomes, and achieve sustainability in rural development.

Background: There is no consensus on the timing of immunotherapeutic strategies for the first-episode anti-myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) associated disorders (MOGAD) presenting with isolated optic neuritis (ON). Objective: To investigate the optimal timing of intravenous methylprednisolone therapy (IVMP) and necessity of immunosuppressive therapy for the first-episode isolated MOG-IgG associated ON (iMOG-ON). Methods: Adult patients with the first-episode iMOG-ON were enrolled. Primary outcomes were best-corrected visual acuity (BCVA) at last follow-up (i.e. final BCVA) and relapse, and their predictors were assessed by multivariate analysis. Results: 62 patients were included. Logistic regression analysis revealed BCVA at the time of IVMP (odds ratio: 0.463 (95 % confidence interval (CI) 0.310-0.714) was a factor predictive of regaining a final BCVA of 0.0 logMAR vision, and its Youden optimal criterion was

Microlenses or arrays are key elements in many applications. However, their construction methods involve multiple fabrication processes, thereby increasing the complexity and cost of fabrication. In this study, we demonstrate an optically anisotropic, electrically tunable liquid crystal (LC) microlens array using a simple, one-step fabrication method. The microlens array is formed via photopolymerization-induced phase separation inside a polymer/LC composite. It possesses both polarization-dependent and electrically tunable focusing and imaging properties. Without applying voltage, the microlens array has a natural focal length of 8 mm, which is a result of its inherent gradient refractive index profile. Upon applying voltage above the threshold, the LC molecules reorient along the electric field direction and the focal length of the microlens array gradually increases. Based on its superior properties, the microlens array is further used for integral imaging applications, demonstrating electrically tunable central depth plane. Such LC microlens arrays could find numerous potential applications owing to their advantageous features of being flat, ultra-thin, and tunable, including 3D displays, optical interconnects, and more.

Multimodal Sentiment Analysis (MSA) is gaining attention, but faces two main challenges: efficient extraction of cross-modal features without redundancy and removing spurious correlations between sentiment labels and multimodal features. In this paper, we propose a novel multimodal learning debiasing model, named Bilateral Cross-modal Debias Multimodal sentiment analysis Model (BCD-MM), to address these issues. Specifically, BCD-MM ultimately enhances the generalisation of the model to out-of-distribution (OOD) situations by improving the ability of cross-modal low-redundancy feature extraction and reducing the reliance on non-causal correlations. First, BCD-MM utilizes an attention score-based method to preserve critical information and eliminate redundancy within modalities. It also employs a gated crossmodal attention mechanism to filter inconsistencies through modal interaction, thereby enhancing the extraction of cross-modal specific features. Second, BCD-MM incorporates a debiasing approach with double bias extraction, using a Tanh-based Mean Absolute Error (TMAE) loss function and inverse probability weighting to mitigate spurious correlations. Finally, extensive testing on three public datasets (MOSI, MOSEI, and SIMS) and two OOD datasets (OOD MOSI and OOD MOSEI) demonstrates our model’s effectiveness in both MSA and debiasing tasks.

Recommendation systems play a pivotal role in delivering user preference information. However, they often face the challenge of information cocoons due to repeated content delivery, particularly prevalent in stock recommendations that are susceptible to investor sentiment. In response to the information cocoons, we propose the Sentiment and Price Combined Model (SPCM), which leverages sentiment features and price factors to predict stock price movements. This novel framework combines collective sentiment analysis with state-of-the-art BERT transformer models and advanced machine learning techniques. Over a three-year period, we collected 40 million stock comments from the Guba platform, extracting investor sentiment conveyed in text information and investigating the impact of metrics such as homophily on stock recommendations. Experimental results indicate that both the volume of posts and the agreement index affect the effectiveness of investor sentiment, while homophily reduces the accuracy of participants’ stock price judgments. The recognition accuracy of the BERT-based sentiment analysis model reaches an impressive 84.12%, and the portfolio constructed by SPCM yields a cumulative return four times that of the industry benchmark. Furthermore, homogeneous quantitative metrics also enhance diversification in stock selection.

Abstract Background Plate design is a necessary and time-consuming operation for GC/LC-MS-based sample preparation. The implementation of the inter-batch balancing algorithm and the intra-batch randomization algorithm can have a significant impact on the final results. For researchers without programming skills, a stable and efficient online service for plate design is necessary. Results Here we describe InjectionDesign, a free online plate design service focused on GC/LC-MS-based multi-omics experiment design. It offers the ability to separate the position design from the sequence design, making the output more compatible with the requirements of a modern mass spectrometer-based laboratory. In addition, it has implemented an optimized block randomization algorithm, which can be better applied to sample stratification with block randomization for an unbalanced distribution. It is easy to use, with built-in support for common instrument models and quick export to a worksheet. Conclusions InjectionDesign is an open-source project based on Java. Researchers can get the source code for the project from Github: https://github.com/CSi-Studio/InjectionDesign . A free web service is also provided: http://www.injection.design .

Inland waterway transport is an important mode of transportation for many countries and regions. Route planning optimization can reduce navigation time, avoid traffic congestion, and improve transportation efficiency. In actual operations, many vessels determine their navigation routes based on the experience of their shipowners. When the captain fails to obtain accurate information, experience-based routes may pose significant navigation risks and may not consider the overall economic efficiency. This study proposes a comprehensive method for optimizing inland waterway vessel routes using automatic identification system (AIS) data, considering the geographical characteristics of inland waterways and navigation constraints. First, AIS data from vessels in inland waters are collected, and the multi-objective Peak Douglas–Peucker (MPDP) algorithm is applied to compress the trajectory data. Compared to the traditional DP algorithm, the MPDP algorithm reduces the average compression rate by 5.27%, decreases length loss by 0.04%, optimizes Euclidean distance by 50.16%, and improves the mean deviations in heading and speed by 23.53% and 10.86%, respectively. Next, the Ordering Points to Identify the Clustering Structure (OPTICS) algorithm is used to perform cluster analysis on the compressed route points. Compared to the traditional DBSCAN algorithm, the OPTICS algorithm identifies more clusters that are both detailed and hierarchically structured, including some critical waypoints that DBSCAN may overlook. Based on the clustering results, the A* algorithm is used to determine the connectivity between clusters. Finally, the nondominated sorting genetic algorithm II is used to select suitable route points within the connected clusters, optimizing objectives, including path length and route congestion, to form an optimized complete route. Experiments using vessel data from the waters near Shuangshan Island indicate that, when compared to three classic original routes, the proposed method achieves path length optimizations of 4.28%, 1.67%, and 0.24%, respectively, and reduces congestion by 24.15%. These improvements significantly enhance the planning efficiency of inland waterway vessel routes. These findings provide a scientific basis and technical support for inland waterway transport.

This paper presents a new type of large-diameter multi-disc soil anchor and its cavity-forming tool. The large-diameter multi-disc soil anchor is obtained by adopting a toothed chain, centrifuging holes to form cavities, forming multiple cavities, placing a steel strand with centering support, injecting cement mortar, and curing. In order to study the uplift bearing characteristics and creep property of the large-diameter multi-plate soil anchor, the equal-diameter soil anchor was taken as the control group. The ultimate pull-out bearing capacity, vertical displacement, axial force, anchor plate bearing load, and side friction resistance were simulated and analyzed by FLAC3D 5.0 64-bit software, and the creep property test of the anchor bolt was carried out. The results show that under the same conditions, the ultimate pulling capacity of the large-diameter multi-disc soil anchor is 125% higher than that of the same-diameter soil anchor. The vertical displacement of the large-diameter multi-disc soil anchor decreases by 51.74% compared with that of the equal-diameter soil anchor when the ultimate uplift capacity is reached. The side friction resistance of the large-diameter multi-disc soil anchor is small and its growth rate is slow. When the ultimate pulling capacity is reached, the load sharing of the anchor disc accounts for 76.54% of the total load applied. The creep rate of the large-diameter multi-plate soil anchor bolt is 0.91 mm, and the creep rate of the equal-diameter soil anchor bolt is 1.69 mm. By fitting the data, it is found that the large-diameter multi-disc soil anchor provides a method to increase the anchorage force of the soil anchor, and the research on its bearing characteristics and creep property provides a theoretical basis for the application of the soil anchor.