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Abstract Due to intermittent renewable energy and fluctuating load demand, distribution networks with renewable distributed generation (DG) installations are more likely to suffer voltage issues and significant power losses. The performance of conservation voltage regulation (CVR) schemes may be adversely affected by the undesirable voltage profile at specific nodes. This paper aims to reduce power losses in CVR‐implemented networks by optimally planning new renewable DGs without changing the existing ones. A scenario‐based optimal renewable DG planning model is proposed with a novel scenario formation method. The uncertainties of load demand and renewables are captured jointly and formed into a finite number of scenarios based on a multivariate Gaussian mixture model (MultiGMM). The locations and capacities of different types of new renewable DGs are optimally planned for CVR performance improvements on power loss saving by aggregating the operation status and probabilities of the scenarios using mixed‐integer non‐linear programming (MINLP). A time‐series simulation is formulated for accuracy verification. The results of case studies show that the proposed model can significantly reduce power losses, active load demand, and reactive load demand. The accuracy of the planning results can be guaranteed with fewer scenarios compared to a widely used classical scenario‐based planning method.

Abstract Purpose Investigate the clinical characteristics of splenomegaly secondary to acute pancreatitis (SSAP) and construct a nomogram prediction model based on Lasso-Logistic regression. Methods A retrospective case-control study was conducted to analyze the laboratory parameters and computed tomography (CT) imaging of acute pancreatitis (AP) patients recruited at Xuanwu Hospital from December 2014 to December 2021. Lasso regression was used to identify risk factors, and a novel nomogram was developed. The performance of the nomogram in discrimination, calibration, and clinical usefulness was evaluated through internal validation. Results The prevalence of SSAP was 9.2% (88/950), with the first detection occurring 65(30, 125) days after AP onset. Compared with the control group, the SSAP group exhibited a higher frequency of persistent respiratory failure, persistent renal failure, infected pancreatic necrosis, and severe AP, along with an increased need for surgery and longer hospital stay (P

Abstract Background Colon cancer remains a major health concern worldwide, with genetic factors playing a crucial role in its development. Toll-like receptors (TLRs) has been implicated in various cancers, but their role in colon cancer is not well understood. This study aims to identify functional polymorphisms in the promoter and 3′UTR regions of TLRs and evaluate their association with colon cancer susceptibility. Methods We conducted a case-control study involving 410 colon cancer patients and 410 healthy controls from the Chinese population. Genotyping of polymorphisms in TLR3, TLR4, TLR5 and TLR7 was performed using PCR-RFLP and TaqMan MGB probes. Using logistic regression analysis, we evaluated the association of TLRs polymorphisms and the susceptibility to colon cancer. To understand the biological implications of the TLR4 rs1927914 polymorphism, we conducted functional assays, including luciferase reporter assay and electrophoretic mobility shift assay (EMSA). Results Our results demonstrated that the G-allele of the TLR4 rs1927914 polymorphism is significantly associated with a decreased risk of colon cancer (OR = 0.68, 95%CI = 0.50–0.91). Stratified analysis showed that TLR4 rs1927914 AG or GG genotype contributed to a decreased risk of colon cancer among younger individuals (OR = 0.52, 95%CI = 0.34–0.81), males (OR = 0.58, 95%CI = 0.38–0.87), non-smokers (OR = 0.58, 95%CI = 0.41–0.83) and non-drinker with OR (95%CI) of 0.66 (0.46–0.93). Functional assays demonstrated that in HCT116 and LOVO colon cancer cells, the luciferase activity driven by the TLR4 promoter with the rs1927914A allele was 5.43 and 2.07 times higher, respectively, compared to that driven by the promoter containing the rs1927914G allele. Electrophoretic mobility shift assay (EMSA) results indicated that the rs1927914G allele enhanced transcription factor binding. Using the transcription factor prediction tool, we found that the G allele facilitates binding of the repressive transcription factor Oct1, while the A allele does not. Conclusion The TLR4 rs1927914 polymorphism influence the susceptibility to colon cancer, with the G allele offering a protective effect through modulation of gene expression. These insights enhance our understanding of the genetic determinants of colon cancer risk and highlight TLR4 as a promising target for cancer prevention strategies.

Abstract Background Lung cancer, with its high morbidity and mortality, presents a major significant public health challenge. CD147, linked to cancer progression and metastasis, is a promising therapeutic target, including for lung cancer. The genetic variation may influence the expression of the gene and consequently the risk of lung cancer. This study aims to investigate single nucleotide polymorphisms (SNPs) in CD147 to understand their association with the risk of developing lung cancer in the Han Chinese population. Methods A hospital-based case–control investigation was conducted, enrolling 700 lung cancer patients and 700 cancer-free controls. TagSNPs were selected using Haploview v4.2, and genotype data from the 1000 Genomes Project database were utilized. The selected SNPs (rs28992491, rs67945626, and rs79361899) within the CD147 gene were evaluated using the improved multiple ligation detection reaction method. Statistical analysis included chi-square tests, logistic regression models, and interaction analyses. Results Baseline characteristics of the study population showed no significant differences in gender distribution between cases and controls, but there was a notable difference in smoking rates. No significant associations were found between the three TagSNPs and lung cancer susceptibility in the codominant model. However, stratification analyses revealed interesting findings. Among females, the rs79361899 AA/AG genotype was associated with an increased risk of lung cancer. In individuals aged ≥ 65 years old, the rs28992491 GG and rs79361899 AA genotypes were linked to a higher susceptibility. Furthermore, an interaction analysis demonstrated significant genotype × gender interactions in the rs79361899 recessive model, indicating an increased lung cancer risk in female carriers of the heterozygous or homozygous polymorphic genotype. Conclusions CD147 polymorphisms play an important role in lung cancer development, particularly in specific subgroup of age and gender. These findings highlight the significance of incorporating genetic variations and their interactions with demographic factors in comprehending the intricate etiology of lung cancer.

To improve the microstructure and properties of Cu-Sn-Ti brazing alloy through component control, the effect of Si on the microstructure and properties of Cu-20Sn-15Ti brazing filler metals was studied using scanning electron microscopy, X-ray diffraction, and EDS energy spectrum analysis. The results show that the microstructure of Cu-20Sn-15Ti brazing filler metal is composed of large-sized polygonal CuSn3Ti5 phase, eutectic structure and α-Cu phase. A small amount of Si (≤ 2.0wt%) refines the polygonal-shaped CuSn3Ti5 phase in the brazing filler metal and generates small-sized Si3Ti5 phase. In contrast, a larger amount of Si (≥ 3.0wt%) differentiates the polygonal-shape CuSn3Ti5 phase, reduces the proportion of eutectic structure, and increases the content and size of the Si3Ti5 phase. When the Si content increases to 5.0wt%, the filler metal no longer generates polygonal-shaped CuSn3Ti5 phase and eutectic structure. Instead, Ti primarily forms Ti5Si3 phase, and the microstructure mainly consists of Ti5Si3 phase, α- Cu phase, Cu41Sn11 phase, and a small amount of strip-shaped CuSn3Ti5 phase. Compared with Cu and Sn, Si has a stronger chemical affinity with Ti and preferentially reacts with Ti to form Ti5Si3 phase. The three-dimensional structure of Ti5Si3 phase is prismatic and exhibits agglomerated growth characteristics. The coarse strip Ti5Si3 phase has central or lateral pore defects, which are mainly related to the growth mechanism. As the Si content increases, the shear strength of the filler metals shows a trend of “increasing-decreasing-increasing”, and the fracture morphology transitions from a mixed morphology of quasi-cleavage fracture and cleavage fracture to cleavage fracture. The CuSn3Ti5 phase is prone to breakage and cracking, becoming the source of cracking. The presence of coarse CuSn3Ti5 phase in different states can deteriorate the shear strength of the brazing filler metals to some extent.

Background: Periodontitis is a chronic progressive disease and the leading cause of tooth loss in adults. Recent studies have shown the impact of oral microbial communities on systemic health and diseases such as cancer, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, diabetes, hypertension, and Alzheimer's disease. In previous case control studies investigatin the relationship between periodontal disease and the oral microbiota, little attention has been paid to the intersections of these domains. Methods: Here, we used high-throughput 16S rRNA sequencing to analyse the differences in the microbial composition in saliva between a group of patients with chronic periodontitis (C; n = 51) and a healthy control group (H; n = 61) and predicted the functional gene composition by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. Results: We found significant alterations in oral microbial diversity between C and H (P = 0.002). Sixteen genera were significantly different between C and H, and 15 of them were enriched in C linear discriminant analysis (LDA > 2). Fifty functional genes were significantly different between C and H, and 34 of them were enriched in C (P < .025). Conclusions: Periodontitis is associated with significant changes in the oral microbial community.

Abstract Studies have suggested that endoplasmic reticulum stress (ERS) is involved in neurological dysfunction and that electroacupuncture (EA) attenuates neuropathic pain (NP) via undefined pathways. However, the role of ERS in the anterior cingulate cortex (ACC) in NP and the effect of EA on ERS in the ACC have not yet been investigated. In this study, an NP model was established by chronic constriction injury (CCI) of the left sciatic nerve in rats, and mechanical and cold tests were used to evaluate behavioral hyperalgesia. The protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that glucose-regulated protein 78 (BIP) and inositol-requiring enzyme 1α (IRE-1α) were co-localized in neurons in the ACC. After CCI, BIP, IRE-1α, and phosphorylation of IRE-1α were upregulated in the ACC. Intra-ACC administration of 4-PBA and Kira-6 attenuated pain hypersensitivity and downregulated phosphorylation of IRE-1α, while intraperitoneal injection of 4-PBA attenuated hyperalgesia and inhibited the activation of P38 and JNK in ACC. In contrast, ERS activation by intraperitoneal injection of tunicamycin induced behavioral hyperalgesia in naive rats. Furthermore, EA attenuated pain hypersensitivity and inhibited the CCI-induced overexpression of BIP and pIRE-1α. Taken together, these results demonstrate that EA attenuates NP by suppressing BIP- and IRE-1α-mediated ERS in the ACC. Our study presents novel evidence that ERS in the ACC is implicated in the development of NP and provides insights into the molecular mechanisms involved in the analgesic effect of EA.

Abstract This paper proposes and investigates a novel 4H‐SiC trench MOSFET (TMOS) with integrated high‐K deep trench and gate dielectric (INHK‐TMOS). The integrated high‐K (INHK) consists of a high‐K gate dielectric and an extended high‐K deep trench dielectric in the drift region. Firstly, the high‐K gate dielectric together with the metal‐forming high‐K metal gate structure, which increases the gate oxide capacitance (COX), reduces the threshold voltage (VTH) and the specific on‐resistance (Ron,sp). Secondly, the extended high‐K deep trench dielectric not only modulates the electric field in the drift region by introducing a new electric field peak at the bottom of the high‐K deep trench dielectric, thereby enhancing the breakdown voltage (BV), but also improves the doping concentration (ND) of the drift region by the assist depletion effect of the high‐K dielectric, further optimizing the forward conduction characteristics. Simulation results demonstrate that when compared to the conventional TMOS, the INHK‐TMOS using HfO2 exhibits a 52.6% reduction in VTH, a 52.1% reduction in Ron,sp, a 20.3% increasement in BV and a 202.3% improvement in figure of merit.

Abstract Hippocampal place cells represent the position of a rodent within an environment. In addition, recent experiments show that the CA1 subfield of a passive observer also represents the position of a conspecific performing a spatial task. However, whether this representation is allocentric, egocentric or mixed is less clear. In this study we investigated the representation of others during free behavior and in a task where female mice learned to follow a conspecific for a reward. We found that most cells represent the position of others relative to self-position (social-vector cells) rather than to the environment, with a prevalence of purely egocentric coding modulated by context and mouse identity. Learning of a pursuit task improved the tuning of social-vector cells, but their number remained invariant. Collectively, our results suggest that the hippocampus flexibly codes the position of others in multiple coordinate systems, albeit favoring the self as a reference point.

On Earth, high-speed rotating blades and rotors experience hypergravity, which is mainly derived from centrifugal force. Aluminum alloys are widely used in high-speed rotating machines. In particular, 7075 aluminum has excellent properties, providing it with great potential for application in high-temperature rotating parts. In this work, the cracking behavior and microstructural evolution characteristics of high-speed rotating blades under different stresses were studied. A specifically designed instrument and blades with multiple necks were assembled, and the stress was tuned by adding weight to the blade tip. Each rotating blade cracked on its root neck, indicating that the gradient hypergravitational force decreased from the root to the tip. The degree of high-temperature cracking obviously increased with a sawtooth-like tip, but the degree of low-temperature cracking did not obviously increase with a smooth tip. A comparison under a constant uniaxial force required a greatly increased ultimate cracking strength that was approximately 10–18 times greater than that under hypergravitational force at the same temperature. Force analysis indicated that the coupling of hypergravitational forces in the normal direction and torsional forces in the tangential direction accelerated cracking. A uniaxial force caused grains to extend along the blade direction. However, a tangential force cut these extended grains to accelerate cracking and grain refining. In this study, real-world simulated service conditions for commercial alloys rotating at high speeds and a new understanding of the mechanical properties of alloys under various severe conditions were provided.

Introduction: Diuretics are the mainstay of maintaining and restoring euvolemia in the management of heart failure. Loop diuretics are often preferred, however, combination diuretic therapy (CDT) with a thiazide diuretic is often used to overcome diuretic resistance and increase diuretic effect. We performed an analysis of the GUIDE-IT study to assess all-cause mortality and time to first hospitalizations in patients necessitating CDT. Methods: Patients from the GUIDE-IT dataset were stratified by their requirement for CDT with a thiazide to achieve euvolemia. A total of 894 patients were analyzed, 733 of which were treated with loop diuretics alone vs 161 used either chlorothiazide or metolazone in addition to loop diuretics. Kaplan-Meir curves were derived with log-rank p-values to evaluate for differences between the groups. Results: There was no significant difference in all-cause mortality regardless of CDT utilization status (mean survival of 612.704 days vs 603.326 days, p = 0.083). On subgroup analysis, there was no significant difference in all-cause mortality amongst those using loop diuretics compared to CDT in the BNP-guided therapy group, (mean survival time 576.385 days vs 620.585 days, p = 0.0523), nor the control group (614.1 days vs 588.9 days; p = 0.5728). Time to first hospitalization was reduced in all using CDT compared to loop diuretics alone (280.5 days vs 407.2 days, p

So as to extend the application of upper bound limit analysis for slope stability in open-pit mine, this paper analyzed failure mechanism of rock mass when shear failure occurred based on plastic mechanics principles, and combined with discrete mathematical theory and least square principle to propose a visualization method of logarithmic spiral. At the same time, the visualization method was applied to engineering practice for slope stability in open-pit mine, and cycle algorithm of stability analysis for open-pit mine slope was proposed through energy balance conditions, then stability analysis results were evaluated reasonably through uniting with limit equilibrium method. The results show that visualization method of logarithmic spiral proposed in this paper is highly consistent with original curve, and can ensure correlation coefficient square is greater than 0.9995. What is more, upper bound limit analysis method has a superhigh accuracy in slope engineering. At the same time, the most dangerous sliding surface obtained by this method can satisfy the requirements of velocity separation, which solved velocity problems during the process of slope evolution. Therefore, the method proposed in this paper has a stronger application in the field of open-pit mining.

The heat transfer characteristics of smooth and honeycomb staggered labyrinth seals were investigated using the conjugate heat transfer method. Three pressure ratios (π = 1.2, 1.6, and 2.0), three rotational speeds (RPM = 0, 10,000, and 20,000), and two wall-to-fluid temperature ratios (TR = 0.4 and −0.67) are considered to explore the influence of centrifugal force and centrifugal buoyancy. The results indicate that the heat transfer coefficient of staggered labyrinth seals increases with pressure ratio due to the increased flow velocity and the thinner boundary layer. As a result of the interaction of inertia force and centrifugal force, some enhancement positions of heat transfer coefficient shift slightly. Notably, centrifugal buoyancy has a negative impact on heat transfer at TR = −0.67, but a positive impact at TR = 0.4. When TR = −0.67, there is a peak of the heat transfer coefficient with increased rotational speed due to centrifugal buoyancy. In addition, the heat transfer coefficient at TR = −0.67 is lower than that at TR = 0.4, especially at high rotational speeds. It is proposed that heat transfer correlations be developed by incorporating the Taylor number and rotating Grachev number.

Objectives To explore a precise control pathway based on patient clinical variations for haemostatic clip usage in laparoscopic cholecystectomy (LC) through on-site research data from a teaching hospital. Specifically, the study aimed to: (1) to calculate the optimal haemostatic clip consumption in LC based on diagnostic grouping and surgical combinations, and (2) to provide evidence for cost containment of high-value medical consumables used in LC.Design Retrospective observational study.Setting Hospital in southwest China.Participants The inclusion criteria were set as inpatients whose medical records included International Classification of Diseases codes 1–3 with code 51.2300 (corresponding to LC surgery) and who were discharged on medical advice. A dataset containing 1001 patients without any haematological diagnoses was collected.Primary and secondary outcome measures Two ordered multinomial logit models were established to identify factors affecting haemostatic clip use in LC. Two-step clustering was used to form subgroups. The premodel included preoperative variables (acute cholecystitis and scarring/fibrotic atrophy), while the full model added intraoperative variables (anatomical variation and severe adhesions). Both models met application prerequisites.Results Key factors influencing haemostatic clip usage were identified, including acute cholecystitis, scarring/fibrotic atrophy, anatomical variation and severe adhesions. Consumption references for haemostatic clips were established for LC patients with good prognoses on discharge. The ordered multinomial logit model revealed that acute cholecystitis decreased the odds of using four or more clips (p

Purpose Performance status (PS), an essential indicator of patients’ functional abilities, is often documented in clinical notes of patients with cancer. The use of natural language processing (NLP) in extracting PS from electronic medical records (EMRs) has shown promise in enhancing clinical decision-making, patient monitoring, and research studies. We designed and validated a multi-institute NLP pipeline to automatically extract performance status from free-text patient notes. Patients and Methods We collected data from 19,481 patients in Harris Health System (HHS) and 333,862 patients from veteran affair’s corporate data warehouse (VA-CDW) and randomly selected 400 patients from each data source to train and validate (50%) and test (50%) the proposed pipeline. We designed an NLP pipeline using an expert-derived rule-based approach in conjunction with extensive post-processing to solidify its proficiency. To demonstrate the pipeline’s application, we tested the compliance of PS documentation suggested by the American Society of Clinical Oncology (ASCO) Quality Metric and investigated the potential disparity in PS reporting for stage IV non-small cell lung cancer (NSCLC). We used a logistic regression test, considering patients in terms of race/ethnicity, conversing language, marital status, and gender. Results The test results on the HHS cohort showed 92% accuracy, and on VA data demonstrated 98.5% accuracy. For stage IV NSCLC patients, the proposed pipeline achieved an accuracy of 98.5%. Furthermore, our analysis revealed a documentation rate of over 85% for PS among NSCLC patients, surpassing the ASCO Quality Metrics. No disparities were observed in the documentation of PS. Conclusion Our proposed NLP pipeline shows promising results in extracting PS from free-text notes from various health institutions. It may be used in longitudinal cancer data registries.

Abstract To elucidate the brain‐wide information interactions that vary and contribute to individual differences in schizophrenia (SCZ), an information‐resolved method is employed to construct individual synergistic and redundant interaction matrices based on regional pairwise BOLD time‐series from 538 SCZ and 540 normal controls (NC). This analysis reveals a stable pattern of regionally‐specific synergy dysfunction in SCZ. Furthermore, a hierarchical Bayesian model is applied to deconstruct the patterns of whole‐brain synergy dysfunction into three latent factors that explain symptom heterogeneity in SCZ. Factor 1 exhibits a significant positive correlation with Positive and Negative Syndrome Scale (PANSS) positive scores, while factor 3 demonstrates significant negative correlations with PANSS negative and general scores. By integrating the neuroimaging data with normative gene expression information, this study identifies that each of these three factors corresponded to a subset of the SCZ risk gene set. Finally, by combining data from NeuroSynth and open molecular imaging sources, along with a spatially heterogeneous mean‐field model, this study delineates three SCZ synergy factors corresponding to distinct symptom profiles and implicating unique cognitive, neurodynamic, and neurobiological mechanisms.

Electro-synthetic fuel is proposed as an approach to achieve net-zero carbon emissions for heavy-duty internal combustion engines and meet carbon neutrality targets. This method is based on high temperature co-electrolysis using a solid oxide electrolysis cell (SOEC) coupled with Fisher-Tropsch (FT) synthesis due to its high efficiency and carbon recycling capacity. To access the techno-economic viability of this pathway and identify the key elements impacting the cost of electro-synthetic fuels, a comprehensive techno-economic model is constructed. This model aims to offer cost cutting guidance and includes SOEC, FT, and techno-economic sub-models, with SOEC and FT validated using literature data. The cost breakdown and sensitivity analysis indicate that heating costs, electricity prices, and stack lifetime are critical factors in reducing the cost of electro-synthetic fuel. Three alternative system layouts that fully utilize thermal and chemical energy are proposed to address the significant heating expense issue. Among these, the optimal system design lowers costs by approximately 5.3 %. Furthermore, this work introduces the contradiction between high performance, high stability, and low-cost accounting for the SOEC lifetime, which is bounded by operating current density. When considering the degradation and replacement of SOEC stacks, the long-term profitability of operating SOEC at a current density of 500 mA/cm2 is superior to that of 850 mA/cm2. Despite the most effective layout being currently unprofitable, it is anticipated that in the future, carbon trade, renewable electricity and technological advancements will drive the cost of electro-synthetic fuel to become competitive with that of diesel.

Abstract Centromere protein A (CENP‐A), a centromere‐specific histone H3 variant, is crucial for kinetochore positioning and chromosome segregation. However, its regulatory mechanism in human cells remains incompletely understood. A structure‐activity relationship (SAR) study of the cell‐cycle‐arresting indole terpenoid mimic JP18 leads to the discovery of two more potent analogs, (+)‐6‐Br‐JP18 and (+)‐6‐Cl‐JP18. Tubulin is identified as a potential cellular target of these halogenated analogs by using the drug affinity responsive target stability (DARTS) based method. X‐ray crystallography analysis reveals that both molecules bind to the colchicine‐binding site of β‐tubulin. Treatment of human cells with microtubule‐targeting agents (MTAs), including these two compounds, results in CENP‐A accumulation by destabilizing Cdh1, a co‐activator of the anaphase‐promoting complex/cyclosome (APC/C) E3 ubiquitin ligase. This study establishes a link between microtubule dynamics and CENP‐A accumulation using small‐molecule tools and highlights the role of Cdh1 in CENP‐A proteolysis.

ABSTRACT: The aim of this study was to examine the effects of NH3 variations across different positions within a cage-reared duck house on the egg production performance and fecal microbiome in Muscovy ducks. Totals of 3,168 female Muscovy ducks (180 ± 2 d) were randomly assigned to 1,056 cages. From d 293 to 300, the egg production rate and levels of NH3, H2S, CO2, temperature, humidity, light intensity, and dust particles were recorded. Two spatial distribution-based experimental classification methods were applied, one grouping ducks into Front, Middle, and End categories, and the other into First, Second, and Third layers. On d 300, serum and feces samples were collected for further analysis. The result showed that both the egg production rate and serum PROG level in the Front were higher than End (P < 0.05). However, no significant differences were found among the First, Second, and Third groups. Among the environmental factors, ammonia (NH3) is a major harmful gas in cage-reared duck houses, with observed concentrations showing a gradient from lower levels in the Front group to higher levels in the Middle group (P < 0.05), and even higher levels in the End group (P < 0.05). Gene sequencing of the 16S rRNA gene revealed a higher relative abundance of Firmicutes in both the Front and Middle groups compared to the End group (P < 0.05). Specifically, within the Firmicutes phylum, the relative abundance of Lactobacillus and Romboutsia was notably higher in the Front group compared to both the Middle and End groups (P < 0.05). What's more, the abundance of Lactobacillus had a negative correlation with NH3 concentration and positive correlation with egg production rate. In conclusion, NH3 concentrations showed variations across different areas of the cage-reared duck house, with higher levels detected at the rear. The elevated NH3 level was identified as the main factor negatively impacting egg production in Muscovy ducks and contributing to a decline in the abundance of Firmicutes, specifically Lactobacillus.

Spectral routing techniques have attracted plenty of research attention for the past decades, as they enable light manipulation in both the frequency domain and the spatial domain, which is crucial for applications in on-chip spectroscopy, optical switching, and modern communications. Here, we demonstrate an ultra-compact asymmetric nanoplasmonic router for communication bands that routes O and C bands to opposite positions. The nanorouter consists of two uneven grooves that create bidirectional scattered optical fields, utilizing the interference between different optical modes inside the grooves. A broadband spectrum exceeding 100 nm and a maximum extinction ratio of 31 dB are achieved, providing new opportunities for nanophotonic color routing solutions and extensions to other areas such as imaging sensors and spectral measurements.

BackgroundImplementing machine learning prediction of negative attitudes towards suicide may improve health outcomes. However, in previous studies, varied forms of negative attitudes were not adequately considered, and developed models lacked rigorous external validation. By analyzing a large-scale social media dataset (Sina Weibo), this paper aims to fully cover varied forms of negative attitudes and develop a classification model for predicting negative attitudes as a whole, and then to externally validate its performance on population and individual levels.Methods938,866 Weibo posts with relevant keywords were downloaded, including 737,849 posts updated between 2009 and 2014 (2009–2014 dataset), and 201,017 posts updated between 2015 and 2020 (2015–2020 dataset). (1) For model development, based on 10,000 randomly selected posts from 2009 to 2014 dataset, a human-based content analysis was performed to manually determine labels of each post (non-negative or negative attitudes). Then, a computer-based content analysis was conducted to automatically extract psycholinguistic features from each of the same 10,000 posts. Finally, a classification model for predicting negative attitudes was developed on selected features. (2) For model validation, on the population level, the developed model was implemented on remaining 727,849 posts from 2009 to 2014 dataset, and was externally validated by comparing proportions of negative attitudes between predicted and human-coded results. Besides, on the individual level, similar analyses were performed on 300 randomly selected posts from 2015 to 2020 dataset, and the developed model was externally validated by comparing labels of each post between predicted and actual results.ResultsFor model development, the F1 and area under ROC curve (AUC) values reached 0.93 and 0.97. For model validation, on the population level, significant differences but very small effect sizes were observed for the whole sample (χ21 = 32.35, p

Background: Organophosphate esters (OPEs) and Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants with common exposure sources, leading to their widespread presence in human body. However, evidence on co-exposure to OPEs and PFAS and its impact on cardiovascular-kidney-liver-metabolic biomarkers remains limited. Methods: In this cross-sectional study, 467 adults were enrolled from January to May 2022 during physical visits in Shijiazhuang, Hebei province. Eleven types of OPEs and twelves types of PFAS were detected, among which eight OPEs and six PFAS contaminants were detected in more than 60% of plasma samples. Seventeen biomarkers were assessed to comprehensively evaluate the cardiovascular-kidney-liver-metabolic function. Multiple linear regression, multipollutant models with sparse partial least squares, and Bayesian kernel machine regression (BKMR) models were applied to examine the associations of individual OPEs and PFAS and their mixtures with organ function and metabolism, respectively. Results: Of the over 400 exposure–outcome associations tested when modelling, we observed robust results across three models that perfluorohexanoic acid (PFHxS) was significantly positively associated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and indirect bilirubin (IBIL). Perfluorononanoic acid was significantly associated with decreased AST/ALT and increased very-low-density lipoprotein cholesterol levels. Besides, perfluorodecanoic acid was correlated with increased high lipoprotein cholesterol and perfluoroundecanoic acid was consistently associated with lower glucose level. BKMR analysis showed that OPEs and PFAS mixtures were positively associated with IBIL and TBIL, among which PFHxS was the main toxic chemicals. Conclusions: Our findings suggest that exposure to OPEs and PFAS, especially PFHxS and PFNA, may disrupt organ function and metabolism in the general population, providing insight into the potential pathophysiological mechanisms of OPEs and PFAS co-exposure and chronic diseases.

Summary: Positive autoregulation (PAR), one type of network motifs, provides a high phenotypic heterogeneity for cells to better adapt to their microenvironments. Typical mechanosensitive proteins can also form PAR, e.g., integrin mediated PAR, but the role of such mechanical PAR in physiological development and pathological process remains elusive. In this study, we found that transforming growth factor β1 (TGF-β1) and integrin levels decrease with tissue softening after the development of paradentium in vivo in rat model of periodontitis (an inflammatory disease with bone defect). Interestingly, TGF-β1 could induce the formation of mechanical PAR involving the integrin-FAK-YAP axis in mesenchymal stem cells (MSCs) by both in vitro experiments and in silico computational model. The computational model predicted a mechanical PAR involving the bimodal distribution of focus adhesions, which enables cells to accurately perceive extracellular mechanical cues. Thus, our analysis of TGF-β1 mediated mechanosensing mechanism on MSCs may help to better understand the molecular process underlying bone regeneration.

ABSTRACT: Mule ducks tend to accumulate abundant fat in their livers via feeding, which leads to the formation of a fatty liver that is several times larger than a normal liver. However, the mechanism underlying fatty liver formation has not yet been elucidated. Fibroblast growth factor 1 (FGF1), a member of the FGF superfamily, is involved in cellular lipid metabolism and mitosis. This study aims to investigate the regulatory effect of FGF1 on lipid metabolism disorders induced by complex fatty acids in primary mule duck liver cells and elucidate the underlying molecular mechanism. Hepatocytes were induced by adding 1,500:750 µmol/L oleic and palmitic acid concentrations for 36 h, which were stimulated with FGF1 concentrations of 0, 10, 100, and 1000 ng/mL for 12 h. The results showed that FGF1 significantly reduced the hepatic lipid droplet deposition and triglyceride content induced by complex fatty acids; it also reduced oxidative stress; decreased reactive oxygen species fluorescence intensity and malondialdehyde content; upregulated the expression of antioxidant factors nuclear factor erythroid 2 related factor 2 (Nrf2), HO-1, and NQO-1; significantly enhanced liver cell activity; promoted cell cycle progression; inhibited cell apoptosis; upregulated cyclin-dependent kinase 1 (CDK1) and BCL-2 mRNA expression; and downregulated Bax and Caspase-3 expression. In addition, FGF1 promoted AMPK phosphorylation, activated the AMPK pathway, upregulated AMPK gene expression, and downregulated the expression of SREBP1 and ACC1 genes, thereby alleviating excessive fat accumulation in liver cells induced by complex fatty acids. In summary, FGF1 may alleviate lipid metabolism disorders induced by complex fatty acids in primary mule duck liver cells by activating the AMPK signaling pathway.

Abstract Deep vein thrombosis (DVT) is a common complication in patients with lower extremity fractures. Once it occurs, it will seriously affect the quality of life and postoperative recovery of patients. Therefore, early prediction and prevention of DVT can effectively improve the prognosis of patients. This study constructed different machine learning models to explore their effectiveness in predicting DVT. Five prediction models were applied to the study, including Extreme Gradient Boosting (XGBoost) model, Logistic Regression (LR) model, RandomForest (RF) model, Multilayer Perceptron (MLP) model, and Support Vector Machine (SVM) model. Afterwards, the performance of the obtained prediction models was evaluated by area under the curve (AUC), accuracy, sensitivity, specificity, F1 score, and Kappa. The prediction performances of the models based on machine learning are as follows: XGBoost model (AUC = 0.979, accuracy = 0.931), LR model (AUC = 0.821, accuracy = 0.758), RF model (AUC = 0.970, accuracy = 0.921), MLP model (AUC = 0.830, accuracy = 0.756), SVM model (AUC = 0.713, accuracy = 0.661). On our data set, the XGBoost model has the best performance. However, the model still needs external verification research before clinical application.

Abstract Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer (LARC) patients with microsatellite stable (MSS) / mismatch repair-proficient (pMMR) tumors is an attractive, but debatable strategy. This phase 2, multicenter, prospective, single-arm study enrolled patients from 6 centers from June 2021 to November 2022. Locally advanced rectal cancer (LARC, cT3-4aN0M0 and cT1-4aN1-2M0) patients aged ≥18 years with the distance from distal border of tumor to anal verge ≤10 cm (identified by Magnetic Resonance Imaging) were qualified for inclusion. The patients received long-course radiotherapy (50 Gy/25 fractions, 2 Gy/fraction, 5 days/week) and three 21-day cycles capecitabine (850–1000 mg/m2, bid, po, day1–14) and three 21-day cycles tislelizumab (200 mg, iv.gtt, day8) as neoadjuvant. Total mesorectal excision (TME) was 6–12 weeks after the end of radiotherapy to achieve radical resection. A total of 50 patients were enrolled in this study. The pathological complete response rate was 40.0% [20/50, 95% confidence interval (CI): 27.61–53.82%], while 15 (30.0%, 95% CI: 19.1–43.75%), 9 (18.0%, 95% CI: 9.77–30.8%), 2 (4.0%, 95% CI: 1.10–13.46%) patients respectively achieved grade 1, 2, and 3 tumor regression. Treatment-related adverse events (TRAEs) occurred in 28 (56.0%) LARC patients, including 26(52.0%) with grade I-II and 2 (4.0%) with grade III (1 with grade 3 immune-related colitis and 1 with grade 3 rash). PD-1 blockade plus long-course chemoradiotherapy (CRT) showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients. A larger randomized controlled study is desired to further validate the above findings.

Oxidation is one of the main failure modes of superalloys, and the initial oxidation of a superalloy provides clues for its failure analysis. NiCo-based superalloys exhibit superior mechanical properties, but their oxidation behaviour is still debatable, especially in terms of the ratio of Ni/Co. Here, we show the effect of the Ni/Co ratio on the initial oxidation behaviour at the nanoscale by in situ environmental transmission electron microscopy (ETEM), which provides the initial microstructural changes in the γ/γ′ structure-based alloy. The results indicate that Ni-rich alloys exhibit better structural stability at high temperatures than Ni-deficient alloys. A high content of Ni promotes the formation of a dense oxide layer, inhibits the oxidation rate, and improves the oxidation resistance. This result will help to elucidate the basic process of oxide formation in NiCo-based single-crystal superalloys and provide ideas for improving their oxidation resistance for alloy design.

ObjectiveAiming at the difficulties of the accuracy maintenance and tracking control of unmanned surface vessels (USVs) operating in narrow lakes and culverts, an intelligent predictive control method for trajectory tracking is proposed on the basis of a self-developed small torpedo-type USV.MethodsFirst, a self-developed nonlinear state space model of the underactuated USV is constructed. An intelligent predictive controller is designed on the basis of the model predictive control design concept and combined with an improved particle swarm optimization （PSO） algorithm to make online decisions, optimize the performance indicators at every moment and correct the predicted state. Finally, simulation and lake tests are carried out to test the tracking performance of the system on reference trajectories, and the tracking performance is compared with that of the linear model predictive controller. ResultsThe results show that the designed intelligent predictive controller has fast response speed, small overshoot and good anti-interference capabilities.ConclusionThe proposed method can not only be applied to the tracking systems of small torpedo-type USVs, but can also provide references for other USV tracking systems.

Abstract Background SARS-CoV-2 infections usually cause immune dysregulation in the human body. Studies of immunological changes resulting from coinfections with Mycobacterium tuberculosis (Mtb) or HIV are limited. Methods We conducted a retrospective study focusing on patients with COVID-19. A total of 550 patients infected with SARS-CoV-2 were enrolled in our study and categorized into four groups based on the presence of coinfections; 166 Delta-infected patients, among whom 103 patients had no coinfections, 52 who were coinfected with Mtb, 11 who were coinfected with HIV, and 384 Omicron-infected patients. By collecting data on epidemiologic information, laboratory findings, treatments, and clinical outcomes, we analyzed and compared clinical and immunological characteristics. Results Compared with those in the Delta group, the median white blood cell, CD4 + T-cell and B-cell counts were lower in the Mtb group and the HIV group. Except for those in the Omicron group, more than half of the patients in the three groups had abnormal chest CT findings. Among the three groups, there were no significant differences in any of the cytokines. Compared with those in the Delta group, the disease duration and LOS were longer in the Mtb group and the HIV group. For unvaccinated Delta-infected patients, in the Mtb and HIV groups, the number of B cells and CD4 + T cells was lower than that in the Delta group, with no significant difference in the LOS or disease duration. In the Mtb group, three (6%) patients presented with a disease duration greater than four months and had decreased lymphocyte and IL17A counts, possibly due to double infections in the lungs caused by SARS-CoV-2 and M. tuberculosis. Conclusions We found that SARS-CoV-2 patients coinfected with Mtb or HIV exhibited a longer disease duration and longer LOS, with a decrease in B cells and CD4 + T cells, suggesting that these cells are related to immune function. Changes in cytokine levels suggest that coinfection with Mtb or HIV does not result in dysregulation of the immune response. Importantly, we discovered a chronic course of coinfection involving more than four months of Mtb and SARS-CoV-2 infection.

Mactra veneriformis is a common economic benthic shellfish with high nutritional value and is widely distributed in the Shandong and Liaoning provinces. Geligang is located in the northern part of Liaodong Bay. It is formed by the water impact of Shuangtaizi and Liaohe River. It has an area of approximately 10 000 hm2 with a fertile substrate. It is an important habitat of beach shellfish, such as M. veneriformis. Studies on the influencing factors of wild population quality traits and their correlation with morphological traits are helpful for developing genetic breeding of marine shellfish. To analyze the effects of morphological traits on quality traits of M. veneriformis at different ages in Geligang, the shell length (SL), shell width (SW), shell height (SH), body weight (BW), and soft tissue wet weight (RW) of 1–3 years old M. veneriformis were analyzed using correlation analysis, path analysis, and multiple regression analysis. The M. veneriformis used in the experiment was obtained from the Geliang in Liaodong Bay in September 2022. A total of 80 1-year-old, 104 2-year-old, and 168 3-year-old M. veneriformis were obtained. The results showed that the morphological traits of M. veneriformis at different growth stages had different contributions to quality traits, and there were significant differences (P < 0.01). SW had the greatest direct effect on the BW of 1–3 year-old M. veneriformis, but had different effects on the RW; SW had the greatest direct effect on 1-year-old M. veneriformis; and SL had the greatest effect on 2- and 3-year-old M. veneriformis. The direct path coefficient of SH to the BW and RW of 2-year-old M. veneriformis did not reach significant level (P > 0.05) and was eliminated. The optimal regression equation of quantitative traits to qualitative traits of 1–3 year-old M. veneriformis was established. The results showed that when BW was the target trait, SW was the main selection trait and SL was the auxiliary selection trait for 1–3 year-old M. veneriformis. When RW was the target trait, SW should be the main selection trait for 1-year-old M. veneriformis, supplemented by SL. The SL should be the main selection trait for both 2- and 3-year-old M. veneriformis, but the SW was the auxiliary selection trait for 2-year-old M. veneriformis, while the SH was for 3-year-old M. veneriformis. In this study, correlation analysis, path analysis, and multiple regression analysis were performed on the morphological traits and quality traits of 1–3 years old M. veneriformis to determine the key morphological traits affecting the quality traits of M. veneriformis at different ages. In this study, the R2 values of the morphological traits of 1- and 2-year-old M. veneriformis (0.898 and 0.859, respectively) were greater than 0.850, indicating that the main factors affecting the body weight of living M. veneriformis were found. However, the R2 value of the morphological traits of 3-year-old M. veneriformis (0.815) was below 0.850, indicating that there may be other influencing traits in addition to the traits analyzed in this study. The reason may be that with the growth of M. veneriformis, the thickness of the shell and the effect on the weight of the living body gradually increase. In this study, the R2 values of morphological traits of 1–3 years old M. veneriformis (0.738, 0.648, and 0.538, respectively) on the wet weight of soft tissue were all below 0.850, indicating that there were other key factors affecting the wet weight of soft tissue. The age of sexual maturity of the M. veneriformis is at 1 year. The development of the gonad in the soft part may be closely related to the size of the wet weight of the soft tissue. The sampling period is mainly in the proliferation to depletion period of the gonad development of M. veneriformis. The gonad development is simultaneously affected by the environment. These results can provide reference for breeding M. veneriformis and the selection of parent shellfish.

This study demonstrates the first work that achieves accurate modeling of Hydrogen plasmatreated (H-treated) p-GaN gate devices with the ASM-GaN model, facilitating simulations for applications in monolithic integrated circuit (IC) design. The workflow for ASM-GaN model parameter extraction and optimization using IC-CAP is proposed. The I-V characteristics of both Enhancement / Depletion (E/D) mode devices are modeled and fitted. The impact of device capacitance on the dynamic properties of monolithic IC is investigated through the ASM model. The results demonstrate that Cds, Cgd, and Cgs have different effects on the monolithic logic circuit performances. The high-level fitting of experimental data and circuit simulation of Inverter, NAND, and Comparator circuits proves the credibility of the modeling workflow and device capacitance modulation. This work provides a method to speed up the GaN monolithic IC design by accurate modeling with fast parameter extraction workflow regardless of the fabrication process. The reliable prediction of the circuit’s dynamic performance will lay the foundation for designing and scaling up the GaN monolithic IC application.

Abstract Background Aslanger’s pattern in electrocardiogram (ECG) indicates that patients may have acute inferior myocardial infarction(AMI) with concomitant critical stenoses on other coronary arteries, which needs to be evaluated the timing of revascularization as risk equivalents of ST elevation myocardial infarction(STEMI). Case Presentation The patient was a 62-year-old male with chief complaint of intermittent exertional subxiphoid pain for 20 days from 30th June. One day after the last episode (19th July), the 18-lead electrocardiogram showed ST segment elevation of 0.05-0.1mV in lead III, ST segment depression in leads I, avL, and V2-V6, T wave inversion with positive terminal vector in lead V4-V5, and positive T wave in lead V6, which indicated Aslanger’s pattern. With increased Troponin I (0.162ng/mL, 0-0.02), The patient was diagnosed as acute non-ST-segment elevation myocardial infarction (NSTEMI) and admitted to coronary ward on 20th July. The coronary angiography showed 95% stenosis in the distal left main coronary artery (LM) to the ostium of the left anterior descending artery (LAD), 90% stenosis in the proximal segment of the LAD, and 80% stenosis in the middle segment of the LAD, and TIMI blood flow was graded score 2. Three drug-eluting stents were implanted at the lesions. The patient’s ECG returned close to normal one month after revascularization. Conclusion We presented an acute coronary syndrome case whose ECG showed with Aslanger’s pattern (i.e., isolated ST-segment elevation in lead III, associated ST-segment depression in lead V4-V6 with positive T wave/terminal vector, and greater ST-segment elevation in lead V1 than in lead V2), and was confirmed severe stenosis of the LM and the proximal segment of the LAD via coronary angiography. In clinical practice, especially in the emergency, patients with ECG presenting Aslanger’s pattern should be urgently evaluated with prompt treatment, and the timing of emergency coronary angiography and revascularization should be evaluated to avoid adverse outcomes caused by delayed treatment.

Non-orthogonal multiple access (NOMA) is a powerful transmission technique that enhances the spectral efficiency of communication links, and is being investigated for 5G standards and beyond. A major drawback of NOMA is the need to apply successive interference cancellation (SIC) at the receiver on a symbol-by-symbol basis, which limits its practicality. To circumvent this, in this paper a novel constructive multiple access (CoMA) scheme is proposed and investigated. CoMA aligns the superimposed signals to the different users constructively to the signal of interest. Since the superimposed signal aligns with the data signal, there is no need to remove it at the receiver using SIC. Accordingly, SIC component can be removed at the receiver side. In this regard and in order to provide a comprehensive investigation and comparison, different optimization problems for user paring NOMA multiple-input-single-output (MISO) systems are considered. Firstly, an optimal precoder to minimize the total transmission power for CoMA subject to a quality-of-service constraint is obtained, and compared to conventional NOMA. Then, a precoder that minimizes the CoMA symbol error rate (SER) subject to power constraint is investigated. Further, the computational complexity of CoMA is considered and compared with conventional NOMA scheme in terms of total number of complex operations. The results in this paper prove the superiority of the proposed CoMA scheme over the conventional NOMA technique, and demonstrate that CoMA is an attractive solution for user paring NOMA MISO systems with low number of BS antennas, while circumventing the receive SIC complexity.

Recent advancements have highlighted the limitations of current quantum systems, particularly the restricted number of qubits available on near-term quantum devices. This constraint greatly inhibits the range of applications that can leverage quantum computers. Moreover, as the available qubits increase, the computational complexity grows exponentially, posing additional challenges. Consequently, there is an urgent need to use qubits efficiently and mitigate both present limitations and future complexities. To address this, existing quantum applications attempt to integrate classical and quantum systems in a hybrid framework. In this article, we concentrate on quantum deep learning and introduce a collaborative classical-quantum architecture called co-TenQu. The classical component employs a tensor network for compression and feature extraction, enabling higher dimensional data to be encoded onto logical quantum circuits with limited qubits. On the quantum side, we propose a quantum-state-fidelity-based evaluation function to iteratively train the network through a feedback loop between the two sides. co-TenQu has been implemented and evaluated with both simulators and the IBM-Q platform. Compared to state-of-the-art approaches, co-TenQu enhances a classical deep neural network by up to 41.72% in a fair setting. In addition, it outperforms other quantum-based methods by up to 1.9 times and achieves similar accuracy while utilizing 70.59% fewer qubits.

Introduction: Despite recent evidence on the surgical outcomes of robotic-assisted surgery (RAS), other patient centre outcomes, including quality of life (QOL), are lacking. This study aims to examine changes in QoL trajectories following RAS across different surgical specialities. Patients and Methods: A prospective cohort study was conducted for patients undergoing urologic, cardiothoracic, colorectal or benign gynaecological RAS, between June 2016 and January 2020 at a tertiary referral hospital in Australia. QoL was measured using the 36-item Short-Form Health Survey at pre-operative, 6 weeks and 6 months postoperatively. Physical and mental summary scores and utility index were primary outcomes, and sub-domains were secondary outcomes. Statistical Analysis Used: Mixed-effects linear regressions were used to determine changes in QoL trajectories. Results: Of the 254 patients undergoing RAS, 154 underwent urologic, 36 cardiothoracic, 24 colorectal and 40 benign gynaecological surgery. Overall, the average age was 58.8 years and most patients were male (75.1%). Physical summary scores significantly decreased from pre-operative to 6 weeks' post-operative in urologic and colorectal RAS; with all surgical specialities at least returning to pre-operative levels within 6 months postoperatively. Mental summary scores consistently increased from pre-operative to 6 months postoperatively for colorectal and gynaecological RAS. Conclusions: RAS contributed to positive changes in QoL, with physical health returning to the pre-operative level and mental health improvements across specialities, in the short term. While degrees of post-operative changes varied amongst specialities, significant improvements demonstrate benefits in RAS.

D-Psicose, as a low-calorie rare sugar, has attracted a lot of attention in recent years for alternating to sucrose. The anti-obesity effect of D-psicose has been extensively confirmed in previous studies, however, the impact of D-psicose on colitis remains vague. Here, we firstly evaluated the effect of the D-psicose prophylactic intervention on dextran sulfate sodium-induced colitis in C57BL/6 mice. The pathological symptoms, inflammatory cytokines levels, gut microbiota composition, short chain fatty acids (SCFAs) production and colonic barrier integrity were comprehensively evaluated. The results confirmed that D-psicose intervention aggravated colitis, characterized by the exacerbation of colon shortening, increase of colonic inflammatory infiltration, and marked exaltation of disease activity indices and IL-6, IL-1β and TNF-α levels. Further, the dysfunction of gut microbiota was identified in the psicose group. The abundance of pro-inflammatory bacteria Lachnospiraceae_NK4A136_group was significantly up-regulated while the abundance of probiotics Akkermansia and Lactobacillus were significantly down-regulated in the psicose group compared to the model group. Moreover, the production of SCFAs was suppressed in the psicose group, accompanied by a decrease in the level of mucin 2 (Muc-2). Collectively, the underlying mechanism of the exacerbation of colitis by D-psicose intervention might be attributed to microbiota dysfunction accompanied by the reduction of SCFAs, which leads to the damage of the mucosal barrier and the intensification of inflammatory invasion.

ABSTRACT: Mule ducks accumulate a large amount of fat in their livers when fed high-energy feed, which is predominantly used for producing fatty livers. Nevertheless, there is limited research on the molecular mechanisms underlying the formation of fatty liver in mule ducks. Fatty acid translocase (CD36) is a sensor for fatty acids and lipid metabolism regulator, which may play a crucial role in the accumulation of fat in the liver of mule ducks. In this study, Overexpression and CD36 gene interference for 24 h was followed by induction of liver cells with 400 µmol/L palmitic acid (PA) for 24 h. The results demonstrated that CD36 overexpression increased hepatic triglyceride content, lipid droplet deposition, oxidative stress, and cell apoptosis. However, interference with CD36 had the opposite effect. CD36 overexpression suppressed the expression of AMPK and CPT-1A genes but enhanced the expression of ACC1 and LKB1 genes, with interference yielding contrasting results. Additionally, the expression of CD36 inhibited the AMPK pathway, reduced AMPK phosphorylation, downregulated AMPK protein expression, and upregulated SREBP1 protein expression. This promoted palmitic acid-induced hepatocyte fat accumulation. In summary, CD36 promotes palmitic acid-induced fat accumulation in primary mule duck liver cells through the AMPK signaling pathway.

Intervertebral disc degeneration (IDD) is widely recognized as the primary culprit of chronic low back pain. Restoring deteriorated intervertebral disc (IVD) and alleviating IDD‐induced low back pain are remaining enormous challenges. There is a genetic susceptibility to IDD, and gene therapy has some therapeutic potential. However, traditional gene therapy still has certain drawbacks, including host immunity, temporary release, and suppression of gene medication function. Although regenerative materials can effectively improve the local microenvironment, they cannot treat IDD from the root. Gene‐functionalized regenerative material (GRM) is constructed based on physical embedding or forming chemical bonds by introducing particular genes, such as pDNA, siRNA, mRNA, and miRNA, into the regenerated materials. The findings demonstrate that GRM not only enhances the safety and controllability of gene therapy, but also effectively repairs IDD by overcoming the constraint that simple regenerative materials cannot reverse the disease's progression from the root. This article provided a brief overview of the physiological and pathological features of the IVD, genetic susceptibility to IDD, available treatment options, and their limitations. Then, the significance of GRM‐based treatment of IDD is proposed, and the future challenges and development in this field are finally prospected.

A small rock shotcrete robot is applied in the deep tunnel dynamic disaster physical simulation system in order to simulate the final operation process of the tunnel project. The robot’s spraying operation and control include many kind of factors. In this paper, the main parameters affecting the spraying operation are analyzed by establishing the spraying model and coating growth model. For matching reasonably the spraying parameters, the matching equation of spraying quality and spraying gun parameter model and spraying feed speed has been derived. Based on the matching equation, the spraying gun structure and robot control system are designed, and the spraying distance and spraying gun movement velocity including horizontal and vertical driving have been controlled better. On the basis of theoretical analysis, a small rock hole shotcrete robot prototype has been developed and the spraying experiments have been finished. The experimental results showed that the model and equation established can guided the spraying quality control. With the increase of the injection elevation angle, the length of the long and short axes of the elliptic coating becomes larger, and the average thickness of the coating center is between 2.23 and 2.34 mm, which meets the design index of the injection robot. The rock hole shotcrete robot meet the design requirements.

Schizophrenia, influenced by genetic and environmental factors, may involve epigenetic alterations, notably histone modifications, in its pathogenesis. This review summarizes various histone modifications including acetylation, methylation, phosphorylation, ubiquitination, serotonylation, lactylation, palmitoylation, and dopaminylation, and their implications in schizophrenia. Current research predominantly focuses on histone acetylation and methylation, though other modifications also play significant roles. These modifications are crucial in regulating transcription through chromatin remodeling, which is vital for understanding schizophrenia's development. For instance, histone acetylation enhances transcriptional efficiency by loosening chromatin, while increased histone methyltransferase activity on H3K9 and altered histone phosphorylation, which reduces DNA affinity and destabilizes chromatin structure, are significant markers of schizophrenia.

Background: China is confronted with the significant menace posed by hemorrhagic fever with renal syndrome (HFRS). Nevertheless, the long-term spatial-temporal variations, regional prevalence patterns, and fundamental determinants' mechanisms for HFRS remain inadequately elucidated. Methods: Newly diagnosed cases of HFRS from January 2004 to December 2019 were acquired from the China Public Health Science Data repository. We used Age-period-cohort and Bayesian Spacetime Hierarchy models to identify high-risk populations and regions in mainland China. Additionally, the Geographical Detector model was employed to quantify the determinant powers of significant driver factors to the disease. Results: A total of 199,799 cases of HFRS were reported in mainland China during 2004–2019. The incidence of HFRS declined from 1.93 per 100,000 in 2004 to 0.69 per 100,000 in 2019. The incidence demonstrated an inverted U-shaped trend with advancing age, peaking in the 50–54 age group, with higher incidences observed among individuals aged 20–74 years. Hyperendemic areas were mainly concentrated in the northeastern regions of China, while some western provinces exhibited a potential upward trend. Geographical detector model identified that the spatial variations of HFRS were significantly associated with the relative humidity (Q = 0.36), forest cover (Q = 0.26), rainfall (Q = 0.18), temperature (Q = 0.16), and the surface water resources (Q = 0.14). Conclusions: This study offered comprehensive examinations of epidemic patterns, identified high-risk areas quantitatively, and analyzed factors influencing HFRS transmission in China. The findings may contribute to the necessary implementations for the effective prevention and control of HFRS.

BackgroundSLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs to the vitamin B12-binding protein family responsible for the cellular uptake of vitamin B12. The role of TCN2 in SLE is still unclear.MethodsWe collected clinical information and blood from 51 patients with SLE and 28 healthy controls. RNA sequencing analysis, qPCR, and western blot confirmed the alteration of TCN2 in disease monocytes. The correlation between TCN2 expression and clinical features and serological abnormalities was analyzed. TCN2 heterozygous knockout THP1 cells were used to explore the effects of TCN2 dysfunction on monocytes. CCK-8 assay and EdU staining were used to detect cell proliferation. ELISA was conducted to assess vitamin B12, glutathione, and cytokines changes. UHPLC-MRM-MS/MS was used to detect changes in the intermediates of the one-carbon cycle. Flow cytometry is used to detect cell cycle, ROS, mitoROS, and CD14 changes.ResultsElevated TCN2 in monocytes was correlated positively with disease progression and specific tissue injuries. Using CD14+ monocytes and TCN2 genetically modified THP1 cell lines, we found that the TCN2 was induced by LPS in serum from SLE patients. TCN2 heterozygous knockout inhibited cellular vitamin B12 uptake and one-carbon metabolism, leading to cell proliferation arrest and decreased Toll-like receptor 4 (TLR4)-mediated CCL2 release. Methionine cycle metabolites, s-adenosylmethionine and homocysteine, rescued these effects, whereas folate treatment proved to be ineffective. Folate deficiency also failed to replicate the impact of TCN2 downregulation on THP1 inflammatory response.ConclusionOur study elucidated the unique involvement of TCN2-driven one-carbon flux on SLE-associated monocyte behavior. Increased TCN2 may promote disease progression and tissue damage by enhancing one-carbon flux, fostering monocyte proliferation, and exacerbating TLR4 mediated inflammatory responses. The inhibition of TCN2 may be a promising therapeutic approach to ameliorate SLE.

For cancer patients, cancer-associated thrombosis (CAT) is a serious complication. An updated epidemiology of CAT over the last ten years is summarized in this review. A comprehensive analysis of pertinent population cohort research released between 2011 and 2024 was carried out. In patients with unselected cancers, the 12-month incidence of CAT is roughly 3-5% (9-fold increase vs to the matched non-cancer population); however, in patients with advanced cancers requiring systemic therapy, the risk rises to 6-8% (20-fold increase vs. to the matched non-cancer population). Anticoagulation use and adherence have improved, but the risk of recurrence is still high, at 5-8% at 6 months and 7-15% at 12 months. The type, stage, and treatment of cancer, a history of venous thromboembolism (VTE), prolonged hospitalization or immobilization, and obesity are significant clinical predictors of the development of CAT. The modified Vienna-CATS and EHR-CAT have the best performance (area under the curve 0.68-0.71) among the clinical risk prediction scores for CAT using the original Khorana score backbone that has been externally validated. However, additional research is required to guarantee appropriate implementation and utilization of these models. Even with contemporary antineoplastic treatments, CAT is still a major complication for cancer patients. We encourage interdisciplinary partnerships among hematologists, data scientists, epidemiologists, and oncologists to guarantee the integration of customized VTE risk evaluation into standard oncologic treatment.

Introduction Spinal cord injury (SCI) is a catastrophic event with devastating physical, social and occupational consequences for patients and their families. The number of patients with acute SCI in China continues to grow rapidly, but there have been no large prospective cohort studies of patients with acute SCI. This proposed study aims to establish a multicentre, extensive sample cohort of clinical data and biological samples of patients in China, which would aid the systematisation and standardisation of clinical research and treatment of acute SCI, thus reducing the heavy burden of acute SCI on patients and society.Methods and analysis The Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study is an observational, multicentre cohort study of patients with acute SCI admitted to the Qilu Hospital of Shandong University and other participating centres with prospective collection of their clinical data and biological samples. We aim to recruit 2097 patients in this study. Demographics, disease history, emergency intervention information, motor and sensory examinations, surgical information, medication information and rehabilitation evaluation will be recorded. This will facilitate the development of a prediction model for complications and prognosis of patients with acute SCI and an evaluation of the current management of acute SCI. Among these variables, detailed information on surgical treatment will also be used to assess procedures for acute SCI treatment. Outcome measurements, including the International Standard for Neurological Classification of Spinal Cord Injury examinations, the occurrence of complications and death, will be performed repeatedly during follow-up. We will analyse imaging data and blood samples to develop SCI imaging markers and biomarkers.Ethics and dissemination This study protocol has been approved by the Medical Ethics Committee of the Qilu Hospital of Shandong University and all other participating centres. The findings will be disseminated in peer-reviewed journals and academic conferences.

Novel strategies in intratumoral injection and emerging immunotherapies have heralded a new era of precise cancer treatments. The affinity of SARS-CoV-2 to ACE2 receptors, a feature which facilitates virulent human infection, is leveraged in this research. Colon cancer cells, with their high ACE2 expression, provide a potentially strategic target for using this SARS-CoV-2 feature. While the highly expression of ACE2 is observed in several cancer types, the idea of using the viral spike protein for targeting colon cancer cells offers a novel approach in cancer treatment. Intratumoral delivery of nucleic acid-based drugs is a promising alternative to overcoming the limitations of existing therapies. The increasing importance of nucleic acids in this realm, and the use of Lipid Nanoparticles (LNPs) for local delivery of nucleic acid therapeutics, are important breakthroughs. LNPs protect nucleic acid drugs from degradation and enhance cellular uptake, making them a rapidly evolving nano delivery system with high precision and adaptability. Our study leveraged a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) combined with a receptor-binding domain from the SARS-CoV-2 spike protein, encapsulated in LNPs, to target colon cancer cells. Our results indicated that the TRAIL fusion-mRNA induced apoptosis in vitro and in vivo. Collectively, our findings highlight LNP-encapsulated TRAIL fusion-mRNA as a potential colon cancer therapy.

Amyotrophic lateral sclerosis (ALS) is a fatal neuromuscular disorder characterized by progressive weakness of almost all skeletal muscles, whereas extraocular muscles (EOMs) are comparatively spared. While hindlimb and diaphragm muscles of end-stage SOD1G93A (G93A) mice (a familial ALS mouse model) exhibit severe denervation and depletion of Pax7+satellite cells (SCs), we found that the pool of SCs and the integrity of neuromuscular junctions (NMJs) are maintained in EOMs. In cell sorting profiles, SCs derived from hindlimb and diaphragm muscles of G93A mice exhibit denervation-related activation, whereas SCs from EOMs of G93A mice display spontaneous (non-denervation-related) activation, similar to SCs from wild-type mice. Specifically, cultured EOM SCs contain more abundant transcripts of axon guidance molecules, including Cxcl12, along with more sustainable renewability than the diaphragm and hindlimb counterparts under differentiation pressure. In neuromuscular co-culture assays, AAV-delivery of Cxcl12 to G93A-hindlimb SC-derived myotubes enhances motor neuron axon extension and innervation, recapitulating the innervation capacity of EOM SC-derived myotubes. G93A mice fed with sodium butyrate (NaBu) supplementation exhibited less NMJ loss in hindlimb and diaphragm muscles. Additionally, SCs derived from G93A hindlimb and diaphragm muscles displayed elevated expression of Cxcl12 and improved renewability following NaBu treatment in vitro. Thus, the NaBu-induced transcriptomic changes resembling the patterns of EOM SCs may contribute to the beneficial effects observed in G93A mice. More broadly, the distinct transcriptomic profile of EOM SCs may offer novel therapeutic targets to slow progressive neuromuscular functional decay in ALS and provide possible ‘response biomarkers’ in pre-clinical and clinical studies.

Introduction: Silicon is a major trace element in humans and a prospective supporting biomaterial to bone regeneration. Submicron silicon pillars, as a representative surface topography of silicon-based biomaterials, can regulate macrophage and osteoblastic cell responses. However, the design of submicron silicon pillars for promoting bone regeneration still needs to be optimized. In this study, we proposed a submicron forest-like (Fore) silicon surface (Fore) based on photoetching. The smooth (Smo) silicon surface and photoetched regular (Regu) silicon pillar surface were used for comparison in the bone regeneration evaluation.Methods: Surface parameters were investigated using a field emission scanning electron microscope, atomic force microscope, and contact angle instrument. The regulatory effect of macrophage polarization and succedent osteogenesis was studied using Raw264.7, MC3T3-E1, and rBMSCs. Finally, a mouse calvarial defect model was used for evaluating the promoting effect of bone regeneration on the three surfaces. Results: The results showed that the Fore surface can increase the expression of M2-polarized markers (CD163 and CD206) and decrease the expression of inflammatory cytokines, including interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Fore surface can promote the osteogenesis in MC3T3-E1 cells and osteoblastic differentiation of rBMSCs. Furthermore, the volume fraction of new bone and the thickness of trabeculae on the Fore surface were significantly increased, and the expression of RANKL was downregulated. In summary, the upregulation of macrophage M2 polarization on the Fore surface contributed to enhanced osteogenesis in vitro and accelerated bone regeneration in vivo.Discussion: This study strengthens our understanding of the topographic design for developing future silicon-based biomaterials.

The restorative benefits of urban green spaces (UGSs) have been supported by many studies. Eight perceived sensory dimensions (PSDs) are regarded as a tool to classify green spaces based on perception. However, little attention has been given to the effects of landscape characteristics (LCs) on the perceived restorativeness (PR) of green spaces. Thus, this study aims to clarify this relationship using the eight PSDs. The research collected information, via video stimulus, from 30 participants on the restorative experiences of urban green parks, according to the eight kinds of PSDs. The skin conductance level obtained via biosensors was used to measure the PR. The subjective satisfaction evaluation of 10 LCs was further obtained using a 5-point Likert scale. The data were analyzed using correlation and regression analyses. The results show that the UGSs with dominant “serene,” “open,” and “sheltered” PSDs are rated highest for restoration. Furthermore, the findings identify the significant factors affecting the restoration of green spaces using different PSDs. In green spaces controlled by PSD, scene, vegetation, water features, and disturbances are more reliable predictors for restoration. The results indicate how different PSD spaces can be distributed in green urban planning and provide key points for designing each PSD for restoration. The use of physiological indexes rather than subjective feelings provides an alternative for demonstrating the restorative benefits of the environment. However, before it can officially be used by designers, more research is needed.