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Help seeking has traditionally been studied in face-to-face settings using self-report instruments measuring learners' internal inclinations for help seeking (eg, perceived benefits and threats). Much less is known about help seeking in online learning. Furthermore, external environmental factors such as a positive climate were found to encourage help seeking. Utilizing peer-help analytics as well as self-report measures, this study simultaneously modelled the structural relationships among students' perceived class climate, internal help-seeking inclinations, help-seeking engagement, participation in peer help and performance in an online class. Results from structural equation modelling indicated that students' perceived goal structure of an online class had a significant influence on their internal help-seeking inclinations, which subsequently affected their help-seeking engagement, participation in peer help and learning outcomes. Instructors of online classes should pay particular attention to fostering a mastery-oriented climate in order to encourage help seeking and improve academic performance.

Abstract Background We aimed to study the prognostic risk factors affecting patients with anaplastic thyroid carcinoma (ATC), develop a clinical prognostic model, and assess patient survival outcomes. Methods Patients with anaplastic thyroid carcinoma from 2000 to 2019 were selected from the Surveillance, Epidemiology, and End Results (SEER) Program to extract the clinical variables used for analysis. The dataset was divided into training (70%) and validation (30%) sets based on a 7:3 ratio. Univariate and LASSO regression analyses were performed on clinical variables from the training set to identify independent prognostic factors. Independent prognostic factors were determined by Univariate and lasso regression according to the clinical variables of the training set, and a nomogram model was established to construct a prognostic model based on the contribution degree of the predictors. The prognostic model was evaluated and internally verified by C-index, ROC curve and calibration curve. Results A total of 713 ATC patients were included in the SEER database. LASSO regression results indicated that age, marital status, race, tumor size, whether the primary lesion was limited to the thyroid gland, surgery, radiotherapy and chemotherapy, were associated with overall survival(OS) prognosis of ATC, and were used to construct nomograms. In the training cohort, the OS nomogram’s C-index was 0.708 (95% CI 0.672–0.745); in the internal validation cohort, the C-index was 0.677 (95% CI 0.620–0.735). ROC curves demonstrated that the OS nomogram exhibits excellent predictive accuracy and discriminative ability. Calibration curves indicated strong consistency between the OS nomogram’s predicted survival rates and actual survival rates. Conclusions We established a survival prediction model for ATC, which can assist clinicians in assessing patient prognosis and making personalized treatment decisions.

Abstract Using acrylic acid advanced ester and styrene as raw materials, the long-chain polyester polymer, polyacrylic acid advanced ester-styrene pour point depressant (P-PPD), was synthesized by molecular design, and its structure was characterized by infrared spectroscopy and nuclear magnetic resonance. In addition, this study experimentally investigated the effect of P-PPD on the phase equilibrium and induction time of natural gas hydrate inhibitors in deionized water (DW) and crude oil/water (O/W) systems, respectively. Polyvinylpyrrolidone (PVP) and mono ethylene glycol (EG) were selected as representatives of kinetic hydrate inhibitor (KHIs) and thermodynamic hydrate inhibitor (THIs), respectively. The results exhibit that P-PPD played a sight role in the phase equilibrium of hydrate, while the addition of P-PPD significantly prolonged the induction time of methane hydrate both in O/W + PVP, OW + EG and O/W + PVP + EG system, indicating that the addition of as-synthesized PPD has a synergistic inhibition effect on the nucleation ability of methane hydrate and can prevent hydrate from formatting during oil and gas transport process, and thus guarantee the flow assurance. The findings of this work will provide a data reference for the hybrid use of hydrate inhibitors and pour point depressants in oil and gas transport.

Abstract Background Gastroesophageal reflux disease (GERD) is among the most common complications of bariatric surgery. This study aimed to analyse the risk factors affecting the worsening of GERD symptoms after laparoscopic sleeve gastrectomy (LSG), and to establish and validate a related nomogram model. Methods The study recruited 236 participants and randomly divided them into training and validation sets in a ratio of 7:3. LASSO regression technique was used to select the optimal predictive features, and multivariate logistic regression was used to construct the column line graphs. The performance of the nomogram was evaluated and validated by analyzing the area under the receiver operating characteristic (ROC) curve, calibration curve, and decision curve. Results In this study, Lasso-logistic regression was applied to select 5 predictors from the relevant variables, which were body mass index (BMI), diabetes, hiatal hernia, GERD, and triglyceride levels. These 5 predictor variables constructed a model with moderate predictive power, with an area under the ROC curve of 0.779 for the training set and 0.796 for the validation set. Decision curve analysis showed that in external validation, if the risk thresholds were between 4 and 98% and 14–95%, then the nomogram can be applied to the clinic. Conclusions We have developed and validated a nomogram that effectively predicts the risk of worsening gastroesophageal reflux symptoms following LSG.

Abstract Background & aims The benefit of postoperative adjuvant transcatheter arterial chemoembolization (pTACE) for patients with hepatocellular carcinoma (HCC), especially those with Child-Pugh (CP) B, remains controversial. This study aimed to assess the survival benefit of pTACE for HCC patients with CP B. Methods Data from 297 HCC patients with CP B7 or B8 were analyzed, dividing them into groups with and without pTACE (70, 23.6% vs. 227, 76.4%). Propensity score matching (PSM) was used to control for confounding bias, and competing-risk regression was applied to address bias from non-cancer-specific death (NCSD). Results Preliminary findings suggest that pTACE did not increase the incidence of severe complications in HCC patients with CP B7 or B8. Survival analysis indicated that the group receiving pTACE had better overall survival and recurrence-free survival than the group without pTACE after PSM. Furthermore, competitive risk analysis revealed that pTACE was an independent prognostic factor associated with reduced cancer-specific death incidence (subdistribution hazard ratio [SHR] 0.644, 95%CI: 0.378–0.784, P = 0.011) and recurrence (SHR 0.635, 95% CI: 0.379–0.855, P = 0.001). Importantly, pTACE did not increase NCSD. Subgroup analysis corroborated these results. Conclusion Adjuvant TACE demonstrates the potential to significantly enhance the long-term prognosis of HCC patients with CP B7 or B8 following hepatectomy, particularly those with multiple tumors, large tumor size, macrovascular or microvascular invasion, and narrow resection margin. Hence, pTACE should be considered for patients at high risk of recurrence following thorough evaluation.

Abstract Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB) are neurodegenerative disorders characterized by the accumulation of α-synuclein aggregates. α-synuclein forms droplets via liquid-liquid phase separation (LLPS), followed by liquid-solid phase separation (LSPS) to form amyloids, how this process is physiologically-regulated remains unclear. β-synuclein colocalizes with α-synuclein in presynaptic terminals. Here, we report that β-synuclein partitions into α-synuclein condensates promotes the LLPS, and slows down LSPS of α-synuclein, while disease-associated β-synuclein mutations lose these capacities. Exogenous β-synuclein improves the movement defects and prolongs the lifespan of an α-synuclein-expressing NL5901 Caenorhabditis elegans strain, while disease-associated β-synuclein mutants aggravate the symptoms. Decapeptides targeted at the α-/β-synuclein interaction sites are rationally designed, which suppress the LSPS of α-synuclein, rescue the movement defects, and prolong the lifespan of C. elegans NL5901. Together, we unveil a Yin-Yang balance between α- and β-synuclein underlying the normal and disease states of PD and DLB with therapeutical potentials.

Abstract Glycan-mediated interactions play a crucial role in biology and medicine, influencing signalling, immune responses, and disease pathogenesis. However, the use of glycans in biosensing and diagnostics is limited by cross-reactivity, as certain glycan motifs can be recognised by multiple biologically distinct protein receptors. To address this specificity challenge, we report the enzymatic synthesis of a 150-member library of site-specifically fluorinated Lewisx analogues (‘glycofluoroforms’) using naturally occurring enzymes and fluorinated monosaccharides. Subsequent incorporation of a subset of these glycans into nanoparticles or a microarray revealed a striking spectrum of distinct binding intensities across different proteins that recognise Lewisx. Notably, we show that for two proteins with unique binding sites for Lewisx, glycofluoroforms exhibited enhanced binding to one protein, whilst reduced binding to the other, with selectivity governed by fluorination patterns. We finally showcase the potential diagnostic utility of this approach in glycofluoroform-mediated bacterial toxin detection by lateral flow.

Abstract High-order diffraction (HOD) from optical microstructures is undesirable in many applications because of the accompanying ghosting patterns and loss of efficiency. In contrast to suppressing HOD with subwavelength structures that challenge the fabrication of large-scale devices, managing HOD is less developed due to the lack of an efficient method for independently manipulating HOD. Here, we report independent manipulation of HODs, which are unexploited for subdiffraction-limit focusing in diffractive lenses, through an analytical formula that correlates the diffraction order and the width of each zone. The large spatial frequencies offered by the HODs enable our lenses to reduce the lateral focal size down to 0.44 λ even without any subwavelength feature (indispensable in most high-NA diffractive lenses), facilitating large-scale manufacture. Experimentally, we demonstrate high-order lens-based confocal imaging with a center-to-center dry resolution of 190 nm, the highest among visible-light confocal microscopies, and laser-ablation lithography with achieved direct-writing resolution of 400 nm (0.385 λ).

Objective There is still a lack of systematic understanding of the evolution process of the Lianzhou Basin since the Mesozoic and its response to karstic development. Methods Based on the comprehensive analysis of the latest field geological investigations, hydrogeological drilling, dissolution experiments, and three-dimensional geological modelling, the tectonic evolution stages of the basin can be divided, and the karstification of each stage can be discussed by considering the existing geological data. Results Before the Cretaceous, carbonate rocks with strong dissolution were successively deposited under the rise or fall movement of the crust, which laid a material foundation for karstic development. The Indosinian movement caused vertically multilayered strata to form an E-W-trending structure, and the Yanshanian movement made the straddle-oblique superimposed a NE-SW-trending structure. They controlled the geological structures, spatial distribution, and dissolution behaviors of carbonate strata. And the distribution of mountains and river system were established. However, karst generally does not develop. An intracontinental and intermountain faulted confluence lake basin formed from the Cretaceous to the Palaeogene, the slow crustal uplift strengthened the karstification around the basin, and it currently retains the early karst platform. Later, they were buried-filled-consolidated by alluvial deposits; therefore, karst basically stopped developing, generating a thick-covered red strata basin. Since the Neogene, the rapid uplift of the crust has led to the continuous elevation of mountains around the basin, deepening of rivers, and strong development of karst, shaping multilevel karst platforms. When part of the Cretaceous red strata in the basin are denuded or cut through, karstification is reactivated. After many changes and penetrations of water systems, the graben basin formed, with karst strata covered by Quaternary sediments, Tectonic evolution controls karstic development, karstification influences the internal structure of the basin, and soil structure causes karst ground collapse. Conclusion This study can provide a scientific basis and guidance for understanding karst collapse conditions in covered karst areas.

Neptunium is one of long-life radioelements, whose speciation in different condition of underground water and soil type, including the adsorption characteristics and adsorption mechanism on some soils, is a critical field. The adsorption behavior of Np(Ⅴ) on muscovite minerals was studied by combining theoretical calculations and static adsorption experiments, providing a reference for evaluating the safety of nuclear waste disposal sites in this work. The adsorption behavior of 239Np(Ⅴ) by different particle sizes of muscovite was studied using characterization methods such as X-ray diffraction(XRD), scanning electron microscopy(SEM), material specific surface area(BET), and NaI(Tl) gamma spectroscopy. Explored the effects of factors such as time, pH value, and the presence or absence of \begin{document}${\mathrm{CO}}_3^{2-} $\end{document} on the adsorption of Np(Ⅴ) by muscovite with different particle sizes. Combining density functional based on first principles, B3LYP was selected as the functional and 6-31G* as the basis group, and quantum chemical calculations were carried out to obtain the dissociation constant(pKa) values of the sites, in order to describe the electronic behavior of the skeleton structure. The experimental results show that different particle sizes of muscovite have an impact on the adsorption of Np(Ⅴ), and the presence or absence of \begin{document}${\mathrm{CO}}_3^{2-} $\end{document} in the environment also affect the adsorption distribution coefficient. However, as the particle size of muscovite decreases, more active sites are exposed, and the trend of adsorption distribution coefficient varies. Based on the SEM image and adsorption distribution coefficient curve, it can be seen that as the grinding mesh size of the sample increases, the end face increases, and even layered muscovite is peeled off. In the alkaline region, the adsorption distribution coefficient slightly increases, but the adsorption distribution coefficient is all less than 100. A small amount of Np(Ⅴ) is enriched in fine-grained to extremely fine-grained minerals, related to finer sediment. The adsorption of Np(Ⅴ) by muscovite is weak and not dominant. Np(Ⅴ) mainly migrates with groundwater in muscovite minerals.

Abstract Background The Naples Prognostic Score (NPS), integrating inflammatory and nutritional biomarkers, has been reported to be associated with the prognosis of various malignancies, but there is no report on intrahepatic cholangiocarcinoma (ICC). This study aimed to explore the prognostic value of NPS in patients with ICC. Methods Patients with ICC after hepatectomy were collected, and divided into three groups. The prognosis factors were determined by Cox regression analysis. Predictive efficacy was evaluated by the time-dependent receiver operating characteristic (ROC) curves. Results A total of 174 patients were included (Group 1: 33 (19.0%) patients; Group 2: 83 (47.7%) patients; and Group 3: 58 (33.3%) patients). The baseline characteristics showed the higher the NPS, the higher the proportion of patients with cirrhosis and Child-Pugh B, and more advanced tumors. The Kaplan-Meier curves reflect higher NPS were associated with poor survival. Multivariable analysis showed NPS was an independent risk factor of overall survival (NPS group 2 vs. 1: HR = 1.671, 95% CI: 1.022–3.027, p = 0.009; NPS group 3 vs. 1: HR = 2.208, 95% CI: 1.259–4.780, p = 0.007) and recurrence-free survival (NPS group 2 vs. 1: HR = 1.506, 95% CI: 1.184–3.498, p = 0.010; NPS group 3 vs. 1: HR = 2.141, 95% CI: 2.519–4.087, P = 0.001). The time ROC indicated NPS was superior to other models in predicting prognosis. Conclusions NPS is a simple and effective tool for predicting the long-term survival of patients with ICC after hepatectomy. Patients with high NPS require close follow-up, and improving NPS may prolong the survival time.

Tumor necrosis factor-α (TNF-α) is a promising target for inflammatory and autoimmune diseases. Spirohypertones A (1) and B (2), two unprecedented polycyclic polyprenylated acylphloroglucinols with highly rearranged skeletons, were isolated from Hypericum patulum. The structures of 1 and 2 were confirmed through comprehensive spectroscopic analysis, single-crystal X-ray diffraction and electronic circular dichroism calculations. Importantly, 2 showed remarkable TNF-α inhibitory activity, which could protect L929 cells from death induced by co-incubation with TNF-α and actinomycin D. It also demonstrated the ability to suppress the inflammatory response in HaCaT cells stimulated with TNF-α. Notably, in an imiquimod-induced psoriasis murine model, 2 restrained symptoms of epidermal hyperplasia associated with psoriasis, presenting anti-inflammatory and antiproliferative effects. This discovery positions 2 as a potent TNF-α inhibitor, providing a promising lead compound for developing an antipsoriatic agent.

Summary: Background: Plasma phospho-tau 217 (pTau217) assays can accurately detect Alzheimer's disease (AD) pathology, but clinical application is limited by the need for specialised equipment. This study tests the performance of a plasma pTau217 assay performed on the Lumipulse-G® platform, that is in widespread clinical use, for selecting patients for therapy based on β-amyloid (Aβ) status and tau staging. Methods: Participants included 388 individuals with 18F-NAV4694 Aβ-PET and 18F-MK6240 tau-PET. Association of pTau217 with PET was examined using Spearman's correlation. Discriminative performance for Aβ and tau PET status as well as tau staging was assessed using Receiver Operating Characteristic analysis. Findings: Plasma pTau217 had a high correlation with both Aβ Centiloid (r = 0.76) and tau SUVRmeta-temporal (r = 0.78). Area under curve (AUC) was 0.93 for Aβ− vs Aβ+ and 0.94 for tau− vs tau+. Applying one threshold (Youden's index), pTau217 was 87% accurate in classification of participants to Aβ− vs Aβ+. Applying two thresholds to classify participants into Low, Indeterminate, and High zones, 17.8% had Indeterminate results and among Low/High zone participants, 92% were correctly classified as Aβ− or Aβ+. The assay accurately discriminated moderate/high neocortical tau from no tau or tau limited to mesial-temporal lobe (AUC 0.97) and high neocortical tau from all others (AUC 0.94). Interpretation: Plasma pTau217, measured by the widely-available, fully-automated Lumipulse®, was a strong predictor of both Aβ and tau PET status and demonstrated strong predictive power in identifying individuals likely to benefit the most from anti-Aβ treatments. Funding: NHMRC grants 1132604, 1140853, 1152623 and AbbVie.

The industry organization theory in the early stage emphasizes the structure-conduct-performance (SCP) paradigm, indicating that industry characteristics and structure factors influence firm performance. Accompanied by technology development and the enhancement of innovation capabilities, the resource-based theory (RBT) has gradually attracted greater attention. Industry structure and competitive forces emphasize the role of external industrial environment factors in influencing a firm's strategic decision-making. Firms employ resources as their competitive advantage to adapt to the industrial environments and to shape the own performance.This study uses hierarchical linear modeling (HLM) to integrate SCP and RBT and to analyze the different levels of effects on firm performance. The integrated theoretical framework suggests multi-level relationships between industry and firm dynamics. Specifically, industry-level factors include industry potential, scale, and dynamics that positively moderate firm-level competitive advantages (innovation resources, organizational resources, and slack resources) and firm performance. The research findings also reveal that industry competitiveness negatively moderates impacts on the relationship between firm competitive advantages and performance. The integration of both industry and firm competitive advantages shapes firm performance.

BackgroundRegulated cell death (RCD) is a genetically controlled form of cell death that plays an important role in organogenesis, tissue remodeling, and pathogenesis of cancers. Transforming growth factor-beta-activation kinase 1 (TAK1) is a member of the serine/threonine protein kinase family, which can respond to internal and external stimuli and participate in inflammatory responses through multiple signaling pathways and cellular processes. In the last two decades, the regulatory roles of TAK1 at the crossroads of multiple RCD pathways, including apoptosis, necroptosis, pyroptosis, and PANoptosis were revealed by 801 articles retrieved from the Web of Science Core Collection database. To analyze global research trends and hotspots concerning the role of TAK1 in RCD, the bibliometric and visualized analysis were applied in the current study.MethodsThe data for this bibliometrics study were retrieved from the Web of Science Core Collection database. The search formula was (TS=(Apoptosis) OR TS=(pyroptosis) OR TS=(Necroptosis) OR TS=(PANoptosis) OR TS=(Autophagy) OR TS=(Ferroptosis) OR TS=(cuproptosis)) AND ((TS=(TAK1)) OR TS=(MAP3K7)). The co-occurrence and co-cited analysis on basic bibliometric parameters were conducted by VOSviewer. The dual-map overlay of journals, citation bursts, keyword timelines, and keyword bursts were analyzed by CiteSpace.ResultsA total of 801 articles from 46 countries have been included in the analysis. The number of publications demonstrates a consistent increase from 1999 to 2024. The primary research institutions driving this field are Osaka University Notably, the Journal of Biological Chemistry stands out as the most popular journal in this domain. These publications collectively involve contributions from 4663 authors, with Jun Tsuji emerging as a prolific author. Jun Tsuji also gains the highest co-citation frequency. Emerging research hotspots are encapsulated by keywords, including apoptosis, NF-κB, inflammation, autophagy, and TNFα.ConclusionThis is the first bibliometric and visualized study to analyze the global trends and hotspots of TAK1 in RCD. Based on the analysis of 801 articles, the results provide a retrospective and comprehensive visualized view of the research hotspots and frontiers of TAK1 at the crossroads of multiple RCD signaling pathways and propose ideas for guiding their future investigations in molecular mechanisms and therapeutic strategies in this field.

Background: Maternal exposure to multiple antibiotics exposure during pregnancy has attracted extensive attention, but biomonitoring studies linking prenatal antibiotic exposure to emotional and behavioural problems in children are limited. Methods: A total of 2475 pregnant women from the Ma’anshan Birth Cohort were included, and the Strengths and Difficulties Questionnaire was completed when their children turned four years of age. The levels of 41 maternal urinary antibiotics and two metabolites were measured during the first, second and third trimesters. Generalized estimating equations and binary logistic regression models were applied to analyse the associations between maternal antibiotic exposure and emotional and behavioural problems in children and to determine the sensitive period, respectively. A quantile-based g-computation (QGC) approach was employed to examine the combined effects of multiple antibiotics on emotional and behavioural problems in children. Results: Overall, florfenicol and preferred-as-veterinary antibiotic (PVA) exposure during pregnancy increased the risk of emotional problems in children, and ofloxacin exposure increased the risk of hyperactivity-inattention. Maternal exposure to trimethoprime, ciprofloxacin, florfenicol, other antibiotics and PVA exposure during the first trimester was positively associated with emotional problems in children. Second-trimester trimethoprime concentrations and third-trimester ciprofloxacin concentrations were positively associated with hyperactivity-inattention. Third-trimester veterinary antibiotic (VA) exposure was negatively associated with hyperactivity-inattention, and second-trimester VA and PVA exposure was negatively associated with peer problems. The QGC model revealed that mixed antibiotic exposure in the first trimester exacerbated the risk of childhood emotional problems (the contribution of ciprofloxacin is prominent), and mixed antibiotic exposure in the second trimester increased the risk of hyperactivity-inattention (the contribution of trimethoprime is prominent). Conclusion: Maternal mixed antibiotic exposure during the first and second trimesters increases the risk of emotional problems and hyperactivity-inattention in children at four years of age.

Background The maternal intrauterine immune environment may affect offspring long‐term health. We aimed to investigate the association between the intrauterine placental immunological milieu and glycolipid metabolic health in children. Methods and Results This study enrolled 1803 mother–child pairs from the Ma'anshan birth cohort (2013–2014). Placental mRNA expression of inflammatory cytokines (interleukin‐1β [IL‐1β], IL‐10, monocyte chemoattractant protein‐1, tumor necrosis factor‐α, IL‐4, IL‐6, IL‐8, C‐reactive protein, and interferon‐γ) and oxidative stress biomarkers (heme oxygenase‐1, hypoxia‐inducible factor‐1alpha, and glucose‐related protein 78) was quantified using real‐time quantitative polymerase chain reaction. Fasting blood glucose, insulin, triglycerides, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, and total cholesterol were assessed at 5 to 6 years old. Statistical analyses included multiple linear regression, binary logistic regression, restricted cubic spline model, and the Bayesian kernel machine regression model. Placental inflammatory cytokines (IL‐1β, monocyte chemoattractant protein‐1, C‐reactive protein, IL‐6, IL‐8, IL‐10) and oxidative stress biomarkers (heme oxygenase‐1, hypoxia‐inducible factor‐1alpha, glucose‐related protein 78) showed positive associations with children's fasting blood glucose levels. Heme oxygenase‐1 and glucose‐related protein 78 exhibited negative correlations with children's fasting insulin levels. Elevated IL‐6, heme oxygenase‐1, hypoxia‐inducible factor‐1alpha, and glucose‐related protein 78 were associated with increased risk of prediabetes in children. Overall upregulation of placental proinflammatory cytokines and oxidative stress factors mRNA expression correlated with higher prediabetes risk in children. Bayesian kernel machine regression analysis indicated a joint positive effect of the 12 placental inflammation and oxidative stress mixtures on children's risk of high fasting blood glucose. Conclusions This exploratory study underscores significant correlations between maternal intrauterine placental inflammation, oxidative stress markers, and offspring fasting blood glucose and insulin levels. These findings highlight the potential role of intrauterine holistic immunity in shaping offspring glucose metabolism health.

Triaxial compression tests were conducted on frozen sandy soils under a constant minimum principal stress (σ3 = 1.6 MPa) and various intermediate principal stresses (σ2 = 1.6, 3.4, 5.2, 7.0, 8.8, 9.8 MPa). The purpose of the research was to investigate the influence of intermediate principal stress on mechanical properties of frozen soil, and to establish a constitutive model to predict the stress-strain relationship of frozen soil under complex stress state. The test results obtained demonstrated that the crack damage stress and failure stress initially increase and then decrease with an increase in the intermediate principal stress. However, the crack initiation stress exhibits an initial increase up to a specific value, after which it stabilizes. From the perspective of crack propagation, the influence mechanism of intermediate principal stress on the strength was discussed. With the variation of stress state, the difference between intermediate principal strain and minimum principal strain gradually increases. The deformation difference was revealed using the stress superposition principle and Poisson's effect. Finally, the constitutive model based on the Weibull distribution and Drucker-Prager strength criterion can accurately represent the stress-strain relationships of frozen sandy soils under true triaxial stress states.

In situ phase separation precipitates play an important role in enhancing the thermoelectric properties of copper sulfides by suppressing phonon transmission. In this study, Cu1.8S composites were fabricated by melting reactions and spark plasma sintering. The complex structures, namely, micron-PbS, Sb2S3, nano-FeS, and multiscale pores, originate from the introduction of FePb4Sb6S14 into the Cu1.8S matrix. Using effective element (Fe) doping and multiscale precipitates, the Cu1.8S+0.5 wt% FePb4Sb6S14 bulk composite reached a high dimensionless figure of merit (ZT) value of 1.1 at 773 K. Furthermore, the modulus obtained for this sample was approximately 40.27 GPa, which was higher than that of the pristine sample. This study provides a novel strategy for realizing heterovalent doping while forming various precipitates via in situ phase separation by natural minerals, which has been proven to be effective in improving the thermoelectric and mechanical performance of copper sulfides and is worth promoting in other thermoelectric systems.

Abstract Multiple Myeloma is an incurable plasma cell malignancy with a poor survival rate that is usually treated with immunomodulatory drugs (iMiDs) and proteosome inhibitors (PIs). The malignant plasma cells quickly become resistant to these agents causing relapse and uncontrolled growth of resistant clones. From whole genome sequencing (WGS) and RNA sequencing (RNA-seq) studies, different high-risk translocation, copy number, mutational, and transcriptional markers can be identified. One of these markers, PHF19, epigenetically regulates cell cycle and other processes and is already studied using RNA-seq. In this study, we generate a large (325,025 cells and 49 patients) single cell multi-omic dataset and jointly quantify ATAC- and RNA-seq for each cell and matched genomic profiles for each patient. We identify an association between one plasma cell subtype with myeloma progression that we call relapsed/refractory plasma cells (RRPCs). These cells are associated with chromosome 1q alterations, TP53 mutations, and higher expression of PHF19. We also identify downstream regulation of cell cycle inhibitors in these cells, possible regulation by the transcription factor (TF) PBX1 on chromosome 1q, and determine that PHF19 may be acting primarily through this subset of cells.

Abstract Background & aims Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. Methods Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. Results Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P

Abstract The axle box of high-speed train adopts double row tapered roller bearings as transmission parts, and the reliability of bearings directly affects the safety of train operation. Tapered roller bearings can withstand axial and radial loads, their service life being closely related to the distribution of contact stress. The test object is the axle box bearing of high-speed train. According to bearing’s structural characteristics, based on the digital speckle correlation method (DSCM) and machine vision, the contact stress distribution detection devices for rollers and complete sets of bearings are developed respectively and an effective detection method is proposed. The contact stress data of the bearing which has reached the service life and the new bearing under the condition of no lubrication and grease lubrication are collected and normalized. Through the geometric relationship, based on the measured data of the selected detection points, the normal and tangential contact stress distribution of the roller and raceway under different contact conditions is obtained by data fitting. The test can be used as an evaluation basis for the effectiveness of bearing modification and provide reference for bearing design.

In the new tunnel under close distance through the existing tunnel risk source, the grouting scheme developed to compensate for stratum losses is still based on empirical methods, relying on the overburden thickness of existing tunnels. This can potentially lead to an excessively high or low probability of uplift of existing tunnels. Proposing a coupled deformation analysis method between the grouting construction and adjacent existing tunnels is of great theoretical significance for developing grouting schemes. In order to reasonably limit the design parameters of grouting construction, based on the theory of fluid–solid coupling elastic pore-column expansion and the theory of random media, the calculation method of stratum displacement which simultaneously considers the coexistence of grout compaction expansion and permeability diffusion mode is derived, and the accuracy of the calculation method is verified by engineering examples. The accuracy of this calculation method was verified through engineering examples. Combined with the deformation coordination condition, the existing tunnel is regarded as an elastic Euler-Bernoulli continuous beam, and the finite element coupling balance equation of the interaction between the existing tunnel and the surrounding soil is obtained. Based on this, a coupling calculation model of the grouting construction and the deformation response of the adjacent existing tunnel is established. Combined with three times of grouting construction examples in the shield tunneling project of Beijing Metro Line 12 under the existing airport line, the reliability of the coupling calculation model to determine the grouting construction parameters is verified. The calculation parameters in the coupling calculation model have clear physical meanings, which can provide a theoretical basis for the grouting design of similar risk source projects.

Abstract In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine’s effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.

Abstract One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues. A Tet-On doxycycline-inducible CAIX expressing cell line was established to mimic various CAIX densities, providing coverage from CAIX-high skrc-59 tumor cells to CAIX-low MMNK-1 cholangiocytes. Assessing the killing of CAR-T cells, we demonstrated that low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250 that was used in the first anti-CAIX CAR-T clinical trial but displayed serious OTOT effects. To assess the therapeutic effect of G9 on patient samples, we generated ccRCC patient derived organotypic tumor spheroid (PDOTS) ex vivo cultures and demonstrated that G9 CAR-T cells exhibited superior efficacy, migration and cytokine release in these miniature tumors. Moreover, in an RCC orthotopic mouse model, G9 CAR-T cells showed enhanced tumor control compared to G250. In summary, G9 has successfully mitigated OTOT side effects and in doing so has made CAIX a druggable immunotherapeutic target.

Abstract Background The caesarean section (CS) rate has increased worldwide and there is an increasing public and scientific interest in the potential long-term health consequences for the offspring. CS is related to persistent aberrant microbiota colonization in the offspring, which may negatively interfere with sex hormone homeostasis and thus potentially affect the reproductive health. It remains unknown whether adult sons’ semen quality is affected by CS. We hypothesize that CS is associated with lower semen quality. Methods This study was based on the Fetal Programming of Semen Quality cohort (FEPOS, enrolled from 2017 to 2019) nested within the Danish National Birth Cohort (DNBC, enrolled from 1996 to 2002). A total of 5697 adult sons of mothers from the DNBC were invited to the FEPOS cohort, and 1044 young men participated in this study. Information on mode of delivery was extracted from the Danish Medical Birth Registry, and included vaginal delivery, elective CS before labor, emergency CS during labor and unspecified CS. The young men provided a semen sample for analysis of semen volume, sperm concentration, motility and morphology. Negative binomial regression models were applied to examine the association between CS and semen characteristics with estimation of relative differences in percentages with 95% confidence intervals (CIs). Results Among included sons, 132 (13%) were born by CS. We found a slightly lower non-progressive sperm motility (reflecting higher progressive sperm motility) among sons born by CS compared to sons born by vaginal delivery [relative difference (95% CI): − 7.5% (− 14.1% to − 0.4%)]. No differences were observed for other sperm characteristics. When CS was further classified into elective CS, emergency CS and unspecified CS in a sensitivity analysis, no significant differences in non-progressive motility were observed among sons born by any of the three types of CS compared to sons born vaginally. Conclusions This large population-based cohort study found no significant evidence for an adverse effect on semen quality in adult sons born by CS.

Based on disappointing results of stem cell-based application in clinical trials for patients with critical limb ischemia, we hypothesized that the acidic environment might be the key factor limiting cell survival and function. In the present study, we used microdialysis to determine presence of acidosis and metabolic imbalance in critical ischemia. Moreover, we explored the effect of extracellular acidosis on adipose-derived stem cells (ADSCs) at molecular and transcriptional level. Our data demonstrate that low pH negatively regulates cell proliferation and survival, also, it results in cell cycle arrest, mitochondrial dynamics disorder, DNA damage as well as the impairment of proangiogenic function in a pH-dependent manner. Further transcriptome profiling identified the pivotal signaling pathways and hub genes in response to acidosis. Collectively, these findings provide strong evidences for a critical role of acidosis in ADSCs impairment with ischemic condition and suggest treatments focus on tissue pH balance and acidosis-mediated hub genes may have therapeutic potential in stem cell-based application.

Nuclear export of the viral ribonucleoprotein (vRNP) is a critical step in the influenza A virus (IAV) life cycle and may be an effective target for the development of anti-IAV drugs. The host factor ras-related nuclear protein (RAN) is known to participate in the life cycle of several viruses, but its role in influenza virus replication remains unknown. In the present study, we aimed to determine the function of RAN in influenza virus replication using different cell lines and subtype strains. We found that RAN is essential for the nuclear export of vRNP, as it enhances the binding affinity of XPO1 toward the viral nuclear export protein NS2. Depletion of RAN constrained the vRNP complex in the nucleus and attenuated the replication of various subtypes of influenza virus. Using in silico compound screening, we identified that bepotastine could dissociate the RAN-XPO1-vRNP trimeric complex and exhibit potent antiviral activity against influenza virus both in vitro and in vivo. This study demonstrates the important role of RAN in IAV replication and suggests its potential use as an antiviral target.

ABSTRACTObjective To investigate the influence of the dead space in disposable blood sampling needle on activated partial thromboplastin time (APTT), FVIII level and pharmacokinetic (PK) profiles in children with hemophilia.Methods Children (

Abstract Aloperine (ALO), a quinolizidine‐type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non‐small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome‐1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO‐induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti‐PD‐L1/TGF‐β bispecific antibody in inhibiting LLC‐derived subcutaneous tumor models. Thus, ALO is first identified as a novel late‐stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A.

Sclerotinia sclerotiorum (Lib.) de Bary is the causative agent of stem white mold disease which severely reduces major crop productivity including soybean and rapeseed worldwide. The current study aimed to explore plant growth-promoting traits and biocontrol of new isolated Bacillus subtilis BS-2301 to suppress S. sclerotiorum through various mechanisms. The results indicated that the BS-2301 exhibited strong biocontrol potential against S. sclerotiorum up to 74% both in dual culture and partition plate experiments. The BS-2301 and its crude extract significantly suppressed S. sclerotiorum growth involving excessive reactive oxygen species (ROS) production in mycelia for rapid death. Furthermore, the treated hyphae produced low oxalic acid (OA), a crucial pathogenicity factor of S. sclerotiorum. The SEM and TEM microscopy of S. sclerotiorum showed severe damage in terms of cell wall, cell membrane breakage, cytoplasm displacement, and organelles disintegration compared to control. The pathogenicity of S. sclerotiorum exposed to BS-2301 had less disease progression potential on soybean leaves in the detached leaf assay experiment. Remarkably, the strain also demonstrated broad-range antagonistic activity with 70%, and 68% inhibition rates against Phytophthora sojae and Fusarium oxysporum, respectively. Furthermore, the strain exhibits multiple plant growth-promoting and disease-prevention traits, including the production of indole-3-acetic acid (IAA), siderophores, amylases, cellulases and proteases as well as harboring calcium phosphate decomposition activity. In comparison to the control, the BS-2301 also showed great potential for enhancing soybean seedlings growth for different parameters, including shoot length 31.23%, root length 29.87%, total fresh weight 33.45%, and total dry weight 27.56%. The antioxidant enzymes like CAT, POD, SOD and APX under BS-2301 treatment were up-regulated in S. sclerotiorum infected plants along with the positive regulation of defense-related genes (PR1-2, PR10, PAL1, AOS, CHS, and PDF1.2). These findings demonstrate that the BS-2301 strain possesses a notable broad-spectrum biocontrol potential against different phytopathogens and provides new insight in suppressing S. sclerotiorum through various mechanisms. Therefore, BS-2301 will be helpful in the development of biofertilizers for sustainable agricultural practices.

G protein-coupled receptor-associated sorting protein 2 (GPRASP2) deficiency has been implicated in immunological inflammation, cancers, and neurological disorders. Our previous work revealed that the pathogenic mutation in GPRASP2 was responsible for X-linked recessive syndromic hearing loss (SHL). Given the specific high expression of GPRASP2 in the spiral ganglion, GPRASP2 likely contributes to the maintenance and functionality of neurons, potentially playing a role in synaptic transmission. The impact of GPRASP2 deficiency on spiral ganglion cells (SGCs) and their underlying pathogenic mechanisms will be investigated in this study. The primary culture of SGCs obtained from mouse cochleae was treated with Gprasp2-targeting short hairpin RNA (Gprasp2-shRNA) via lentivirus infection. The results showed that GPRASP2 deficiency enhanced SGCs apoptosis and decreased cell viability. Meanwhile, a significant abnormality of mitochondrial morphology and decreased membrane potential were observed in GPRASP2-deficient SGCs. These effects could be mitigated by treatment with the mitochondrial division inhibitor 1 (Mdivi-1). In addition to enhancing SGCs apoptosis and decreasing cell viability, GPRASP2 deficiency also inhibited the development of SGCs in mouse cochlear explant culture. Our study further revealed that this deficiency resulted in increased phosphorylation of AMPK and activation of the AMPK/DRP1 pathway, promoting SGCs apoptosis. These findings provide insight into the pathogenic mechanisms by which GPRASP2 deficiency is implicated in auditory dysfunction.

Plant parasitic nematodes (PPNs) pose a significant threat to global crop productivity, causing an estimated annual loss of US $157 billion in the agriculture industry. While synthetic chemical nematicides can effectively control PPNs, their overuse has detrimental effects on human health and the environment. Biocontrol agents (BCAs), such as bacteria and fungi in the rhizosphere, are safe and promising alternatives for PPNs control. These BCAs interact with plant roots and produce extracellular enzymes, secondary metabolites, toxins, and volatile organic compounds (VOCs) to suppress nematodes. Plant root exudates also play a crucial role in attracting beneficial microbes toward infested roots. The complex interaction between plants and microbes in the rhizosphere against PPNs is mostly untapped which opens new avenues for discovering novel nematicides through multi-omics techniques. Advanced omics approaches, including metagenomics, transcriptomics, proteomics, and metabolomics, have led to the discovery of nematicidal compounds. This review summarizes the status of bacterial and fungal biocontrol strategies and their mechanisms for PPNs control. The importance of omics-based approaches for the exploration of novel nematicides and future directions in the biocontrol of PPNs are also addressed. The review highlighted the potential significance of multi-omics techniques in biocontrol of PPNs to ensure sustainable agriculture.

Summary: The resected pⅢA-N2 non-small-cell lung cancer (NSCLC) patients who could benefit from postoperative radiotherapy (PORT) are not well-defined. The study explored the role of PORT on EGFR mutant and wild-type NSCLC patients. We retrospectively searched for resected pIIIA-N2 lung adenocarcinoma patients who underwent EGFR mutation testing. 80 patients with EGFR wild-type and 85 patients with EGFR mutation were included. 62 patients received PORT. In overall population, the median disease-free survival (DFS) was improved in PORT arm compared to non-PORT arm (22.9 vs. 16.1 months; p = 0.036), along with higher 2-year locoregional recurrence-free survival (LRFS) rate (88.3% vs. 69.3%; p = 0.004). In EGFR wild-type patients, PORT was associated with a longer median DFS (23.3 vs. 17.2 months; p = 0.044), and a higher 2-year LRFS rate (86.8% vs. 61.9%; p = 0.012). In EGFR mutant patients, PORT was not significantly correlated with improved survival outcomes. EGFR wild-type may a biomarker to identify the cohort that benefits from PORT.

Partially aromatic polyamides owing to their excellent thermal stability are widely used in high temperature applications, however, like their aliphatic counterparts, they are readily flammable and more challenging to process. In this work, several organophosphorus flame retardants were synthesized and compounded with partially aromatic polyamide and evaluated for their processability, thermal, and fire behaviour. The compounds containing a commercial flame retardant, Exolit® OP 1230 (EX), and two new flame retardants, namely 1,4-phenylenebis(diphenylphosphine oxide) (MP) and (1,1′-biphenyl]-4,4′-diylbis(diphenylphosphine oxide) (BP), showed self-extinguishing capability (i.e., UL94 V0 class) with 4 wt% phosphorus (P) loading, together with a substantial reduction in the pHRR (up to 47 %), with respect to the pristine PAP. Rheological measurements on extended timescales were used to assess the melt stability of partially aromatic polyamide compounds. The presence of MP and BP in the polymer matrix did not trigger any excessive degradation phenomena such as chain scission, branching, or crosslinking reactions, thus, allowing a stable processability similar to a pristine partially aromatic polyamide sample. Finally, analysis of evolved gases during thermal decomposition revealed that MP and BP mainly exert a flame inhibition effect quite early in the decomposition process.

ObjectiveTo investigate the impact of diaphragmatic breathing combined with limb training on lower limb lymphedema following surgery for gynecological cancer.MethodsFrom January 2022 to May 2022, 60 patients with lower limb lymphedema post-gynecologic cancer surgery were chosen. They were split into a control group (n = 30) and a treatment group (n = 30). The control group underwent complex decongestive therapy (CDT) for managing lower limb lymphedema after gynecologic cancer surgery, while the treatment group received diaphragmatic breathing combined with limb coordination training alongside CDT. Both groups completed a 4-week treatment regimen. The lower limb lymphedema symptoms were evaluated using the genital, lower limb, buttock, and abdomen (GCLQ) scores; bilateral lower limb circumference measurements; and anxiety and depression scores.ResultsCompared to sole CDT administration, individuals undergoing diaphragmatic breathing coupled with limb coordination training experienced notable reductions in scores for the self-perceived symptom assessment questionnaire (GCLQ), bilateral lower limb circumference, as well as anxiety and depression scores.ConclusionThe incorporation of diaphragmatic breathing combined withalongside limb coordination training can accelerate and augment the efficacy of treating lower limb lymphedema post-gynecologic cancer surgery.