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Abstract Reduced nitric oxide (NO) bioavailability is a pathological link between obesity and Alzheimer’s disease (AD). Obesity-associated metabolic and mitochondrial bioenergetic dysfunction are key drivers of AD pathology. The hypothalamus is a critical brain region during the development of obesity and dysfunction is an area implicated in the development of AD. NO is an essential mediator of blood flow and mitochondrial bioenergetic function, but the role of NO in obesity-AD is not entirely clear. We investigated diet-induced obesity in female APPswe/PS1dE9 (APP) mouse model of AD, which we treated with two different NO donors (sodium nitrite or L-citrulline). After 26 weeks of a high-fat diet, female APP mice had higher adiposity, insulin resistance, and mitochondrial dysfunction (hypothalamus) than non-transgenic littermate (wild type) controls. Treatment with either sodium nitrite or L-citrulline did not reduce adiposity but improved whole-body energy expenditure, substrate oxidation, and insulin sensitivity. Notably, both NO donors restored hypothalamic mitochondrial respiration in APP mice. Our findings suggest that NO is an essential mediator of whole-body metabolism and hypothalamic mitochondrial function, which are severely impacted by the dual insults of obesity and AD pathology.

Abstract Early T-cell precursor lymphoblastic leukemia/lymphoma (ETP-ALL/LBL) is a distinct subtype of T-ALL/LBL, characterized by a poor response to initial chemotherapy, a high relapse rate, and an inferior outcome. The treatment options for ETP-ALL/LBL are currently limited, and there are no reported clinical trials available for ETP-ALL/LBL. From June 2018 to June 2022, we conducted a single-arm, single-center, phase 2 trial (NCT03553238) in newly diagnosed ETP-ALL/LBL (age 14–55). Patients (N = 54) received pediatric-inspired chemotherapy plus tucidinostat, which was orally administered once daily at a dosage of 10 mg from induction to consolidation therapy. The primary endpoint was 3 year event-free survival (EFS). Secondary endpoints were overall survival (OS), relapse-free survival (RFS), complete remission rate and adverse events. The composite complete remission (CRc, complete response [CR] plus complete response with incomplete blood count recovery [CRi]) rate and MRD negativity after induction therapy was 91% (49 of 54 patients) and 65% (35 of 54 patients), respectively. The MRD negativity after consolidation was achieved in 87% patients (47 of 54 patients). With a median follow-up of 39.3 months (IQR, 20.6 to 60.0), the 3 year EFS rate was 67.7% (95% CI 56.2–81.7), the 3 year OS rate was 71.5% (95% CI 60.2–84.9) and the 3 year RFS rate was 67.5% (95% CI 55.9–81.6). The most common grade 3–4 adverse events were neutropenia (94%), anemia (85%), thrombocytopenia (76%), and infection (53%). Tucidinostat plus pediatric regimen is an effective and well-tolerated regimen for new diagnosed ETP-ALL/LBL, with high CRc and MRD negativity rates, as well as encouraging survival outcomes.

Abstract Introduction Newer neuraxial local anesthetic agents which have been used as epidural analgesia have shown to provide reliable pain relief during labor. Ropivacaine and levobupivacaine are newer agents now used for labor analgesia. However, even though few studies have made their comparison with bupivacaine, ropivacaine and levobupivacaine have seldom systematically been compared. Therefore, in this analysis, we aimed to systematically show the impact of epidural ropivacaine versus levobupivacaine for labor analgesia on maternal and fetal outcomes. Methods http://www.clinicaltrials.gov , Web of Science, MEDLINE, EMBASE, Cochrane database and Google Scholar were searched for studies comparing ropivacaine versus levobupivacaine for labor analgesia. Maternal and fetal outcomes were considered as the endpoints in this analysis. The RevMan software 5.4 was used to analyze data in this study. Risk ratio (RR) with 95% confidence intervals (CI) were used to represent the data post analysis. Results A total number of 2062 participants were included in this analysis whereby 1054 participants were assigned to ropivacaine and 1008 participants were assigned to levobupivacaine. The main results of this analysis showed that epidural ropivacaine was not associated with significantly higher risk of hypotension (RR: 0.71, 95% CI: 0.43 – 1.17; P = 0.18) and pruritus (RR: 1.12, 95% CI: 0.89 – 1.42; P = 0.34) when compared to levobupivacaine for labor analgesia. However, the risk of nausea and vomiting was significantly higher with ropivacaine (RR: 1.60, 95% CI: 1.05 – 2.44; P = 0.03). Spontaneous vaginal delivery (RR: 0.99, 95% CI: 0.89 – 1.42; P = 0.83), instrumental vaginal delivery (RR: 1.13, 95% CI: 0.89 – 1.45; P = 0.32) and the risk for cesarean section (RR: 0.76, 95% CI: 0.42 – 1.37; P = 0.35) were not significantly different. When fetal outcomes were assessed, Apgar score

Abstract Purpose To investigate whether the body composition parameters can be employed as potential biomarkers for predicting the progression risk of chronic kidney disease (CKD). Materials and methods Four hundred sixteen patients diagnosed with CKD were included in this retrospective study. Patients with a greater than 50% decline in estimated glomerular filtration rate or progression to end-stage kidney disease were in the high-risk group, otherwise, they were in a low-risk group. Body composition area, the index, and radiodensities in the Hounsfield unit (HU), which reflect the degree of X-ray absorption, were measured on abdominal CT images. Risk factors in body composition and clinical parameters of CKD were identified by Cox regression and utilized to construct the nomogram. The performance of the nomogram was assessed using time receiver operating characteristics curves, calibration curves, and decision curve analysis. Results There were 254 patients in low-risk group and 162 in high-risk group (268 males, 148 females, mean age: 55.89 years). Urea, diabetes, 24 h-urinary protein, mean arterial pressure, and subcutaneous adipose tissue radiodensity (SATd) were valuable indicators for predicting the high-risk group. The area under curve values for the nomogram of training/validation set at 1 year, 2 years, and 3 years were 0.805/0.753, 0.784/0.783, and 0.846/0.754, respectively. For diabetic CKD patients, extra attention needs to be paid to visceral to subcutaneous fat ratio and renal sinus fat radiodensity. Conclusion SATd was the most valuable noninvasive indicator of all body composition parameters for predicting high-risk populations with CKD. The nomogram we constructed has generalization with easily obtainable indicators, good performance, differentiation, and clinical practicability. Critical relevance statement Radiodensity rather than an area of adipose tissue can be used as a new biomarker of prognosis for CKD patients, providing new insights into risk assessment, stratified management, and treatment for CKD patients. Key Points Obesity is an independent risk factor for the development and prognosis of CKD. Adipose tissue radiodensity is more valuable than fat area in prognosticating for kidney disease. Parameters that prognosticate in diabetic CKD patients are different from those in other CKD patients. Graphical Abstract

Abstract Background Obesity is a growing health concern in China, closely linked to metabolic disorders such as type 2 diabetes. Laparoscopic Sleeve Gastrectomy (LSG) is effective in promoting weight loss and improving metabolic outcomes. Emerging evidence highlights the role of gut microbiota in metabolic regulation, yet the specific alterations in gut microbiota and their association with metabolic changes post-surgery in Chinese patients remain unclear. Understanding these shifts could provide key insights into optimizing treatment strategies for metabolic improvement following bariatric surgery. Methods Stool samples and clinical data were collected from 30 obese patients before and 6 months after surgery. The composition of the gut microbiota was analyzed through 16S rRNA sequencing, and Spearman correlation analysis was used to determine the association between gut microbiota and clinical indicators. Results The analysis of 30 patients showed a significant decrease in Body Mass Index (BMI) (36.75 ± 4.09 kg/m2 vs 26.37 ± 3.47 kg/m2, p

Abstract Background Delayed diagnosis of inflammatory bowel disease (IBD) is common, there is still no effective imaging system to distinguish Crohn's Disease (CD) and Ulcerative Colitis (UC) patients. Methods This multicenter retrospective study included IBD patients at three centers between January 2012 and May 2022. The intestinal and perianal imaging signs were evaluated. Visceral fat information from CT images was extracted, including the ratio of visceral to subcutaneous fat volume (VSR), fat distribution, and attenuation values. The valuable indicators were screened out in the derivation cohort by binary logistic regression and receiver working curve (ROC) analysis to construct an imaging report and data system for IBD (IBD-RADS), which was tested in the validation cohort. Results The derivation cohort included 606 patients (365 CD, 241 UC), and the validation cohort included 155 patients (97 CD, 58 UC). Asymmetric enhancement (AE) (OR = 87.75 [28.69, 268.4]; P

Abstract Tetracyclines (TCs) rank second globally in the use of animal infection therapy and animal husbandry as growth promoters among all antibiotics. However, large amounts of TCs residue in food products and more than 75% of TCs are excreted into the environment, causing adverse effects on the ecological system and human health. It has been challenging to simultaneously realize low-cost, rapid, and highly selective detection of TCs. Here, inspired by the fluorogenic reactions between resorcinol and catecholamines, we find the fluorescence quenching ability of tetracycline (TC) and firstly propose a fluorescent “turn-off” detection of TC using dopamine and 4-fluororesorcinol. The optimal reaction condition for the fluorescent assay is investigated and the optimized probe showed a good limit of detection (LOD of 1.7 µM) and a wide linear range (10 µM to 350 µM). Moreover, this fluorescent assay proved to be an effective tool for detecting TC in river, Sprite, and beer samples, which represent the aquatic environments and food and may contain tetracyclines residues. Finally, the high selectivity of the method for TC has been confirmed by eliminating the interference from common substances. The proposed strategy provides a high-efficiency and selective solution for the detection of TCs in environment and food and the application fields of this fluorescent assay could be further expanded in the future.

Abstract Introduction In congenital aniridia caused by mutations in paired box 6 (PAX6), PAX6 influences the migration and differentiation of limbal epithelial cells (LECs), thereby playing a pivotal role in aniridia-associated keratopathy. The antidepressants ritanserin and duloxetine affect PAX6 expression in LECs. Limbal stromal cells, which support limbal epithelial stem cells, are crucial in the limbal stem cell niche. This study explores how ritanserin and duloxetine influence gene expression in primary human limbal stromal cells from subjects with congenital aniridia and from healthy subjects, in vitro. Methods Primary human limbal stromal cells from corneas affected by aniridia (AN-LSCs) (n = 8) and from healthy corneas (LSCs) (n = 8) were isolated and cultured in either low-glucose serum-free (LGSF) or normal-glucose serum-containing (NGSC) media. Cells were treated with 4 µM ritanserin or duloxetine for 24 h. Quantitative PCR (qPCR) and western blot were used to assess the expression of PAX6, FOSL2, TGF-β1, ACTA2A1, LUM, COL1A1, COL5A1, DSG1, FABP5 and ADH7. Results In AN-LSCs with LGSF-medium, ritanserin increased PAX6 messenger RNA (mRNA) (p = 0.007) and decreased TGF-β1 and FOSL2 mRNA levels (P = 0.005, P = 0.038). In addition, TGF-β1 protein levels decreased with both treatments (P = 0.02, P = 0.007), and FABP5 protein level increased, using ritanserin (P = 0.019). In LSCs with LGSF-medium, ACTA2A1 mRNA levels decreased using ritanserin and duloxetine (P = 0.028; P = 0.031), while FABP5 mRNA levels increased with ritanserin treatment (P = 0.003). Also, duloxetine use reduced α-SMA protein (P = 0.013) and increased FABP5 protein levels (P = 0.029). In LSCs with NGSC-medium, ritanserin elevated LUM, FABP5 and ADH7 mRNA and protein levels (P = 0.025, P = 0.003, P = 0.047, P = 0.024, P = 0.013, P = 0.039). Conclusions The results of our study confirmed that the antipsychotropic drugs ritanserin and duloxetine alter PAX6 and TGF-β1 gene expression in AN-LSCs cultured in LGSF-medium. These drugs were found to have an impact on retinoic acid signaling pathways and keratocyte characteristic markers both in LSCs and AN-LSCs, using different culture media.

Abstract To address the stable grasping control issue in manipulator grasping systems, this manuscript proposes an improved multiverse optimizer‐based anti‐saturation model‐free adaptive control (IMVO‐AS‐MFAC) algorithm. Initially, the manuscript converts the manipulator grasping system into an equivalent data model through dynamic linearization techniques. Then, based on the dynamic linearization model, the IMVO‐AS‐MFAC controller is designed. To address the actuator saturation problem that commonly occurs during the clamping process of manipulator grasping systems, a saturation parameter is introduced into the IMVO‐AS‐MFAC algorithm. Meanwhile, the controller parameters are optimized using an improved multiverse optimizer algorithm, which involves modifications to the initial population distribution and location update strategy. The improved algorithm demonstrates more competitive optimization performance compared to the traditional multiverse optimizer. The major advantage of the IMVO‐AS‐MFAC algorithm lies in the fact that only the input and output data of the manipulator grasping system are required throughout the entire control process, and the controller parameters are derived using an optimization algorithm rather than relying on empirical knowledge. Furthermore, rigorous mathematical analysis confirms the stability of the IMVO‐AS‐MFAC approach, and its effectiveness is validated through semi‐physical experiments conducted in an environment integrating the MATLAB/Simulink module and the RecurDyn platform.

Abstract Metal micro/nanoparticle ink-based printed circuits have shown promise for promoting the scalable application of flexible electronics due to enabling superhigh metallic conductivity with cost-effective mass production. However, it is challenging to activate printed metal-particle patterns to approach the intrinsic conductivity without damaging the flexible substrate, especially for high melting-point metals. Here, we report a pressure-constrained sonication activation (PCSA) method of the printed flexible circuits for more than dozens of metal (covering melting points from room temperature to 3422 °C) and even nonmetallic inks, which is integrated with the large-scale roll-to-roll process. The PCSA-induced synergistic heat-softening and vibration-bonding effect of particles can enable multilayer circuit interconnection and join electronic components onto printed circuits without solder within 1 s at room temperature. We demonstrate PCSA-based applications of 3D flexible origami electronics, erasable and foldable double-sided electroluminescent displays, and custom-designed and large-area electronic textiles, thus indicating its potential for universality in flexible electronics.

Abstract Metastasis has been one of the primary reasons for the high mortality rates associated with tumours in recent years, rendering the treatment of current malignancies challenging and representing a significant cause of recurrence in patients who have undergone surgical tumour resection. Halting tumour metastasis has become an essential goal for achieving favourable prognoses following cancer treatment. In recent years, increasing clarity in understanding the mechanisms underlying metastasis has been achieved. The concept of premetastatic niches has gained widespread acceptance, which posits that tumour cells establish a unique microenvironment at distant sites prior to their migration, facilitating their settlement and growth at those locations. Neutrophils serve as crucial constituents of the premetastatic niche, actively shaping its microenvironmental characteristics, which include immunosuppression, inflammation, angiogenesis and extracellular matrix remodelling. These characteristics are intimately associated with the successful engraftment and subsequent progression of tumour cells. As our understanding of the role and significance of neutrophils in the premetastatic niche deepens, leveraging the presence of neutrophils within the premetastatic niche has gradually attracted the interest of researchers as a potential therapeutic target. The focal point of this review revolves around elucidating the involvement of neutrophils in the formation and shaping of the premetastatic niche (PMN), alongside the introduction of emerging therapeutic approaches aimed at impeding cancer metastasis.

Abstract Lattice oxygen in metal oxides plays an important role in the reaction of diesel oxidation catalysts, but the atomic-level understanding of structural evolution during the catalytic process remains elusive. Here, we develop a Mn2O3/SmMn2O5 catalyst using a non-stoichiometric exsolution method to explore the roles of lattice oxygen in NO oxidation. The enhanced covalency of Mn–O bond and increased electron density at Mn3+ sites, induced by the interface between exsolved Mn2O3 and mullite, lead to the formation of highly active lattice oxygen adjacent to Mn3+ sites. Near-ambient pressure X-ray photoelectron and absorption spectroscopies show that the activated lattice oxygen enables reversible changes in Mn valence states and Mn-O bond covalency during redox cycles, reducing energy barriers for NO oxidation and promoting NO2 desorption via the cooperative Mars-van Krevelen mechanism. Therefore, the Mn2O3/SmMn2O5 exhibits higher NO oxidation activity and better resistance to hydrothermal aging compared to a commercial Pt/Al2O3 catalyst.

Objectives: Diamond tools are crucial in stone processing, and their performance is directly related to processing quality and cost. With the rise of stone and labor costs, the performance requirements on diamond tools are also increasing, including sharpness, self sharpening, tool life, and cutting efficiency. To improve efficiency and reduce costs, users often increase the cutting machine power and speed, which further requires diamond tools to have higher sharpness and strength at the risk of breakage. A practical method method is to increase the content of tin (Sn) in the segment to enhance its brittleness without changing the diamond concentration and particle size. However, an increase in Sn content will reduce the strength of the segment and may lead to a decrease in the holding force between CuSn alloy and diamond. For example, the commonly used CuSn10 and CuSn15 pre alloy powders in industry have low strength and weak holding force on diamond. Therefore, it is necessary to improve the powder properties and processing technology. Methods: Adding Zn element to CuSn10 alloy powder can improve powder strength and holding force. CuSnZn-x alloy powder (mass fraction of Zn, x=10.00%, 15.00%, 20.00%, 25.00%, 30.00%) was prepared by atomization process. The hot pressing sintering temperatures were 610 ℃, 615 ℃, 630 ℃, 645 ℃, 655 ℃, and the sintering pressure was 21 MPa. The melting temperature of CuSnZn alloy powder was tested using a differential thermal analyzer. The density of the sintered segment was tested using Archimedes drainage method. The bending strength of the sintered segment was tested using mechanical performance testing equipment. The Rockwell hardness of the sintered segment was measured using a Rockwell hardness tester. The microstructure morphology of the sintered segment and its fracture were analyzed using scanning electron microscopy. Other performances of samples with different Zn contents were analyzed and compared as well, namely theoretical density, Rockwell hardness, and flexural strength, to study the influence of Zn content on sample microstructure. Results: With the increase of Zn content, the rate of decrease in melting temperature of CuSnZn alloy powder first increases and then decreases. When the Zn mass fraction is 30%, the melting temperature decreases to 848 ℃, which is 164 ℃ lower than that of CuSn10. As the Zn content increases, the brass in the sintered segment gradually transforms from the α phase to the α+β phase and then the α+β+β´ phase, resulting in a significant increase in the Rockwell hardness of the segment. The bending strength of the sintered segment first increases and then decreases, reaching a maximum value of 542 MPa when the Zn mass fraction is 20.00%. When the mass fraction of Zn is 10.00% and 15.00%, obvious toughness dimples are observed on the fracture surface of the sintered segment, and particle peeling is observed on the fracture surface. The peeling surface is smooth and flat, indicating grain boundary peeling fracture of the phase structure. When the mass fraction of Zn is 20.00% and 25.00%, a large number of cleavage fracture surfaces are observed on the fracture surface of the sintered segment, and a small amount of smooth concave transgranular fracture is observed, which is partially intergranular fracture and partially transgranular fracture. When the mass fraction of Zn is 30.00%, the fracture surface of the sintered segment is flat and smooth, and the crack passes through the phase interface and grain along the hard and brittle structure, which is transgranular fracture. Conclusions: Adding Zn element can effectively reduce the melting point of alloy powder, and with the increase of Zn content, the hardness of sintered samples increases while the toughness decreases. When the Zn content is 30.00%, the melting temperature of CuSnZn alloy powder reaches its minimum value. When the Zn content exceeds 25.00%, the strength of the sintered samples will gradually decrease. Therefore, in actual production, the appropriate amount of Zn addition and sintering process should be selected based on comprehensive consideration of demand.

The rapid development of the global economy and population growth are accompanied by the production of numerous waste textiles. This leads to a waste of limited resources and serious environmental pollution problems caused by improper disposal. The rational recycling of wasted textiles and their transformation into high-value-added emerging products, such as smart wearable devices, is fascinating. Here, we propose a novel roadmap for turning waste cotton fabrics into three-dimensional elastic fiber-based thermoelectric aerogels by a one-step lyophilization process with decoupled self-powered temperature–compression strain dual-parameter sensing properties. The thermoelectric aerogel exhibits a fast compression response time of 0.2 s, a relatively high Seebeck coefficient of 43 μV·K−1, and an ultralow thermal conductivity of less than 0.04 W·m−1·K−1. The cross-linking of trimethoxy(methyl)silane (MTMS) and cellulose endowed the aerogel with excellent elasticity, allowing it to be used as a compressive strain sensor for guessing games and facial expression recognition. In addition, based on the thermoelectric effect, the aerogel can perform temperature detection and differentiation in self-powered mode with the output thermal voltage as the stimulus signal. Furthermore, the wearable system, prepared by connecting the aerogel-prepared array device with a wireless transmission module, allows for temperature alerts in a mobile phone application without signal interference due to the compressive strains generated during gripping. Hence, our strategy is significant for reducing global environmental pollution and provides a revelatory path for transforming waste textiles into high-value-added smart wearable devices.

Integrase strand transfer inhibitors (INSTIs) have emerged as the first-line choice for treating human immunodeficiency virus (HIV) infection due to their superior efficacy and safety. However, the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV (PLWH) is not fully understood due to limited data. In this study, we conducted a cross-sectional examination of PLWH receiving antiretroviral therapy, with a specific focus on HIV-positive men who have sex with men (MSM) on INSTI-based regimens (n = 61) and efavirenz (EFV)-based regimens (n = 28). Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging (MRI) scans, including T1-weighted images and resting-state functional MRI. Compared to the EFV group, the INSTI group exhibited primarily reduced gray matter volume (GMV) in the right superior parietal gyrus, higher regional homogeneity (ReHo) in the left postcentral gyrus, lower ReHo in the right orbital part of the inferior frontal gyrus, and increased voxel-wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus. Furthermore, the analysis revealed a main effect of antiretroviral drugs on GMV changes, but no main effect of neuropsychiatric disorders or their interaction. The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group, validating the initial findings. Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI-based regimens compared to those on EFV-based regimens. These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI-based regimens.

Abstract Background Precursor B-cell acute lymphoblastic leukemia (B-ALL) is the most common cancers in children. Failure of induction chemotherapy is a major factor leading to relapse and death in children with B-ALL. Given the importance of altered metabolites in the carcinogenesis of pediatric B-ALL, studying the metabolic profile of children with B-ALL during induction chemotherapy and in different minimal residual disease (MRD) status may contribute to the management of pediatric B-ALL. Methods We collected paired peripheral blood plasma samples from children with B-ALL at pre- and post-induction chemotherapy and analyzed the metabolomic profiling of these samples by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). Healthy children were included as controls. We selected metabolites that were depleted in pediatric B-ALL and analyzed the concentrations in pediatric B-ALL samples. In vitro, we study the effects of the selected metabolites on the viability of ALL cell lines and the sensitivity to conventional chemotherapeutic agents in ALL cell lines. Results Forty-four metabolites were identified with different levels between groups. KEGG pathway enrichment analyses revealed that dysregulated linoleic acid (LA) metabolism and arginine (Arg) biosynthesis were closely associated with pediatric B-ALL. We confirmed that LA and Arg were decreased in pediatric B-ALL samples. The treatment of LA and Arg inhibited the viability of NALM-6 and RS4;11 cells in a dose-dependent manner, respectively. Moreover, Arg increased the sensitivity of B-ALL cells to L-asparaginase and daunorubicin. Conclusion Arginine increases the sensitivity of B-ALL cells to the conventional chemotherapeutic drugs L-asparaginase and daunorubicin. This may represent a promising therapeutic approach.

Abstract Background: The rise of network pharmacology has led to the widespread use of network-based computational methods in predicting drug target interaction (DTI). However, existing DTI prediction models typically rely on a limited amount of data to extract drug and target features, potentially affecting the comprehensiveness and robustness of features. In addition, although multiple networks are used for DTI prediction, the integration of heterogeneous information often involves simplistic aggregation and attention mechanisms, which may impose certain limitations. Results: MSH-DTI, a deep learning model for predicting drug-target interactions, is proposed in this paper. The model uses self-supervised learning methods to obtain drug and target structure features. A Heterogeneous Interaction-enhanced Feature Fusion Module is designed for multi-graph construction, and the graph convolutional networks are used to extract node features. With the help of an attention mechanism, the model focuses on the important parts of different features for prediction. Experimental results show that the AUROC and AUPR of MSH-DTI are 0.9620 and 0.9605 respectively, outperforming other models on the DTINet dataset. Conclusion: The proposed MSH-DTI is a helpful tool to discover drug-target interactions, which is also validated through case studies in predicting new DTIs.

Abstract Objectives The purpose of this study is to assess the diagnostic efficacy of contrast-enhanced CT scans for small bowel bleeding. Methods This retrospective study evaluated patients diagnosed with non-neoplastic small intestinal bleeding (including duodenum) who underwent abdominal CT at our institution from December 2013 to March 2023. Patients were categorized into diverticulum and non-diverticulum groups based on the cause of bleeding. Active bleeding was defined on the CT images as extravasation of contrast material in the intestinal lumen during the arterial phase and/or progressive accumulation of contrast material during the venous phase. We have documented the original report (extracted from the medical record system and additional consultation opinions from senior radiologists), including the presence of active bleeding and its potential bleeding location. Furthermore, two radiologists reassessed the CT images, seeking consensus on the diagnosis between them. Results The study included 165 patients, predominantly male, with a median age of 30 years. Active bleeding was identified in 48.3% of patients. Notably, all identified bleeding diverticula in the diverticulum group exhibited cul-de-sac termination. Among the identified causes of bleeding, Crohn’s disease was most prevalent (46.7%, N of causes = 64). Significant differences were observed in the diagnostic methods between the diverticulum and non-diverticulum groups, with surgery predominantly applied in the diverticulum group, and endoscopy in the non-diverticulum group (n = 49 vs n = 15, p = 0.001). Contrast agent extravasation was significantly higher in the diverticulum group (n = 54 vs n = 16, p = 0.001), and Meckel’s diverticulum cases appearing tubular were significantly higher than in other diverticulum cases (n = 25 vs n = 3, p

Abstract Non-Hermitian physics has emerged as a new paradigm that profoundly changes our understanding of non-equilibrium systems, introducing novel concepts such as exceptional points, spectral topology, and non-Hermitian skin effects (NHSEs). Most existing studies focus on non-Hermitian eigenstates, whereas dynamic properties have been discussed only recently, and the dynamic NHSEs are not yet confirmed in experiments. Here, we report the experimental observation of non-Hermitian skin dynamics using tunable one-dimensional nonreciprocal double-chain mechanical systems with glide-time symmetry. Remarkably, dynamic NHSEs are observed with various behaviors in different dynamic phases, which can be understood via the generalized Brillouin zone and the related concepts. Moreover, the observed dynamic NHSEs, amplifications, bulk unidirectional wave propagation, and boundary wave trapping provide promising ways to manipulate waves in a controllable and robust way. Our findings open a new pathway toward non-Hermitian dynamics, which will fertilize the study of non-equilibrium phases of matter.

Abstract The beveling process is an important process in the manufacturing of resonators, which has a significant impact on the frequency stability of resonators. Without understanding the frequency characteristics of the resonator after beveling, it is impossible to accurately design the beveled resonators. Thus, in order to investigate the vibration characteristics of AT-cut beveled resonators, we investigated the high-frequency vibration in this work by using the subregional geometric fitting method (SGFM) based on Mindlin’s plate theory. Quartz crystal plates with nonuniform thicknesses are partitioned into three regions and each region is fitted by using the polynomial functions based on the measured geometric morphology data. The governing equations are obtained based on Mindlin’s two-dimensional theory and the coupled vibrations are further solved using the partial differential equation module of COMSOL. In the numerical calculation, we compare the results obtained by the SGFM with those obtained by the global fitting method and the measured data. The accuracy and effectiveness of the SGFM are also verified. It is found that the frequencies obtained by the SGFM are slightly higher than the frequencies obtained by the global fitting method, and the results of SGFM are closer to the measured results. Meanwhile, as the beveling time increases, the frequency increases and the energy trapping effect becomes more significant. The proposed method can significantly improve the computational efficiency of thickness-shear vibration while ensuring accuracy. It is expected to provide a new geometric fitting method for the analysis of beveled crystal resonators.

Abstract Stable vortex lattices are basic dynamical patterns which have been demonstrated in physical systems including superconductor physics, Bose-Einstein condensates, hydrodynamics and optics. Vortex-antivortex (VAV) ensembles can be produced, self-organizing into the respective polar lattices. However, these structures are in general highly unstable due to the strong VAV attraction. Here, we demonstrate that multiple optical VAV clusters nested in the propagating coherent field can crystallize into patterns which preserve their lattice structures over distance up to several Rayleigh lengths. To explain this phenomenon, we present a model for effective interactions between the vortices and antivortices at different lattice sites. The observed VAV crystallization is a consequence of the globally balanced VAV couplings. As the crystallization does not require the presence of nonlinearities and appears in free space, it may find applications to high-capacity optical communications and multiparticle manipulations. Our findings suggest possibilities for constructing VAV complexes through the orbit-orbit couplings, which differs from the extensively studied spin-orbit couplings.

Objectives: Heart failure is a stage of various cardiovascular diseases and constitutes a growing major public health problem worldwide. Nurse-led heart failure clinics play an important role in managing heart failure. All nurse-led heart failure clinic services are clinic-based. We conducted a systematic review to describe the contents and impact of nurse-led heart failure clinics. Methods: A review of nurse-led heart failure clinic research was undertaken in PubMed, Embase, Web of Science, and Cochrane Library. The search was initially conducted on October 23, 2022 and updated on November 21, 2023. Articles were appraised using the Joanna Briggs Institute Appraisal criteria by two independent reviewers. This review was registered on PROSPERO (CRD42022352209). Results: Twelve articles were included in this systematic review. The nurse-led heart failure clinic contents were: medication uptitration, educational counselling, evidence-based transitional care, psychosocial support, physical examination and mental well-being assessment, therapy monitoring and adjustment, follow-up, and phone consultations. Most studies reported largely positive clinical outcomes in nurse-led heart failure clinics. Four studies examined the quality of life and reported conflicting results; four studies examined medication titration efficacy, and the results were generally positive. Only two studies examined cost-effectiveness. Conclusions: Nurse-led heart failure clinics have shown a largely positive impact on patient outcomes, quality of life, and medication titration efficacy. More randomised controlled trials and other studies are needed to obtain more robust conclusions.

Abstract Background The management of locally recurrent gynecological carcinoma remains a challenge due to the limited availability of data. This study aims to share our institutional experience in using definitive radiotherapy (RT) for the treatment of locally recurrent cervical and endometrial carcinoma. Methods The study retrospectively reviewed 20 patients in our hospital completing salvage 3D image-based HDR brachytherapy, with or without EBRT, for locally recurrent cervical and endometrial carcinoma after surgery. The Kaplan–Meier method was applied to estimate the disease-free survival (DFS) and overall survival (OS). The toxicities were assessed by CTCAEv5. Results During a median observation period of 21 months, the study reported a tumor objective response rate of 95%. The 3-year DFS and OS rates were 89.4% and 90.9%, respectively. The EBRT combined with brachytherapy achieved a median cumulative dose of 88 Gy to CTV D90. 14 patients received concurrent and/or systemic chemotherapy. Two patients suffered locoregional recurrence after salvage treatment, one of whom only received salvage brachytherapy for prior RT history. The analysis identified significant predictors for DFS, including tumor histology and FIGO stage. 5 patients observed acute grade 1–2 rectal (15%) or genitourinary (10%) toxicities. Late toxicities including grade 1–2 rectal bleeding (10%) and grade 2 pelvic fracture (5%) were seen in 3 patients. Conclusions 3D image-guided brachytherapy combined with EBRT shows effective tumor control and acceptable toxicity profile for women with locally recurrent gynecologic cancer. The success in managing vaginal recurrence is notably influenced by histologic subtype and FIGO staging.

Abstract Objective To test the glycemic susceptibility in three urological cancers and eight urological/reproductive diseases using the Mendelian randomization (MR) method. Materials and methods Two-sample MR was applied to investigate the causal role of three glycemic traits (type II diabetes, fasting glucose and glycated hemoglobin (HbA1c)) in eleven urological/reproductive diseases (kidney cancer, bladder cancer, prostate cancer, kidney/ureter stone, urinary incontinence, benign prostatic hyperplasia, erectile dysfunction, female infertility, male infertility, abnormal spermatozoa and polycystic ovary syndrome). Further multivariate MR (MVMR) and mediating analysis were performed to investigate the associations. Results Among all the 11 diseases, type II diabetes was positively associated with erectile dysfunction, which was stable across both cohorts [odds ratio (OR): 1.59, 95% confidence interval (CI): 1.15–2.20, P = 0.005 for FinnGen Biobank and OR: 1.14, 95% CI: 1.08–1.21, P

To reduce the corrosion rate of biodegradable magnesium alloys, n-MgO/Mg–Zn–Ca composites (SR-3ZXM) were prepared using nano-MgO (n-MgO) reinforcement and screw rolling (SR). n-MgO addition and SR refined the grain size and improved the passivation ability and corrosion resistance of SR-3ZXM. After SR, adding n-MgO reduced the corrosion current density of SR-3ZXM to 20.99 μA/cm2. The corrosion rate calculated based on the material weight loss decreased to 0.88 mm/y, which is attributed to the grain size refinement and variation of secondary phase fraction. Thus, n-MgO addition and SR change the corrosion mechanism and improve the corrosion resistance of SR-3ZXM.

Subclinical hypothyroidism (SCH) is closely related to insulin resistance, and thyroid-stimulating hormone (TSH) level is an independent factor for insulin resistance associated with subclinical hypothyroidism. This study aims to explore the effects of TSH levels on insulin signal transduction in adipocytes and to establish the role of endoplasmic reticulum (ER) stress in this process. In this study, the SCH mouse model was established, and 3T3-L1 adipocytes were treated with TSH or tunicamycin (TM), with or without 4-phenylbutyric acid (4-PBA), an inhibitor of ER stress. Subclinical hypothyroidism mice exhibited impaired glucose tolerance, inactivation of the IRS-1/AKT pathway, and activation of the IRE1/JNK pathway in adipose tissue, which can all be alleviated by 4-PBA. Supplementation with levothyroxine restored the TSH to normal, alongside alleviated ER stress and insulin resistance in SCH mice, which is characterized by improved glucose tolerance, decreased mRNA expression of IRE1, and decreased phosphorylation of JNK in adipose tissue. In 3T3-L1 adipocytes, TSH induces insulin resistance, leading to a decrease in glucose uptake. This effect is mediated by the downregulation of IRS-1 tyrosine phosphorylation, reduced AKT phosphorylation, and inhibited GLUT4 protein expression. Notably, all these effects can be effectively reversed by 4-PBA. Moreover, TSH induced TNF-α and IL-6 production and upregulated the expression of ER stress markers. Similarly, these changes can be recovered by 4-PBA. These findings indicate that TSH has the capability to induce insulin resistance in adipocytes. The mechanism through which TSH disrupts insulin signal transduction appears to involve the ER stress–JNK pathway.

Abstract The present investigation examines the usage of rectangular multi-injectors for fuel injection in a supersonic combustion chamber. To evaluate the fuel jet penetration and distribution, a computational method is applied to model the supersonic compressible flow with cross multi-fuel jets released from annular rectangular nozzles with different nozzle configurations. The main effort of this work is to evaluate the jet interactions in the existence of cross-supersonic flow. Fuel jet penetration and distribution are evaluated for three proposed injector arrangements to attain the more efficient option for better fuel mixing. Our results show that reducing injector space improves fuel mixing inside the combustor via creation of strong vortices. Beside, injection of air from internal nozzle increase fuel interactions and fuel mixing inside combustion chamber.

Abstract Background The relationship between metformin use and prostate cancer (PCa) risk has yet to be clear despite more than a decade of debate on this topic. Hence, we aimed to investigate the causal role of metformin in reducing PCa risk through an up-to-date comprehensive genome-wide analysis. Methods We employed validated instrument variables of metformin use derived from a prior high-quality study, including five potential targets (AMPK, GCG, GDF15, MCI and MG3). Mendelian randomization (MR) analysis was performed to harmonize genetically predicted metformin use and PCa phenotypes. PCa phenotypes were from two large genome-wide association studies (GWAS), the Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome (PRACTICAL) and the FinnGen cohort. Seven methods were applied to generate MR results: the inverse variance weighted (IVW), IVW with multiplicative random effects, MR-Egger, MR-Egger (bootstrap), weighted median, simple mode and weighted mode. Strict sensitivity analysis was conducted to satisfy core assumptions of MR design. Results We enrolled 32 significant single nucleotide polymorphisms (SNPs) that involved with metformin use. Nearly all targets yielded insignificant primary results (IVW with multiplicative random effects), except that AMPK target posed a positive effect on PCa risk from FinnGen cohort [odds ratio (OR): 6.09, 95% confidence interval (CI): 1.10-33.53, P value: 0.038]. The general effect of metformin use, comprising all 5 targets, also yielded negative results (random-effect meta-analysis with OR: 1.09, 95% CI: 0.76–1.58, P value: 0.637 for PRACTICAL; OR: 2.55, 95% CI: 0.58–11.16, P value: 0.215 for FinnGen). None of the sensitivity analyses provided support for a causal association between metformin use and PCa risk. Conclusion This up-to-date study did not support the protective role of metformin in reducing PCa risk, considering each target, overall effect, and sensitivity analysis. It is imperative to reflect on the presumed “almighty medicine” and ongoing phase III trials are anticipated to assess the anti-neoplasm effect of metformin.

Nanoscratching introduces detrimental surface and subsurface defects like amorphous regions, dislocations, and stacking faults in monocrystalline silicon, hindering its application in microelectronics and high-performance optics. This study leverages in-situ transmission electron microscopy to unveil the thermal evolution of these defects in atomic scale. A key finding is the amorphous phase recrystallization starting at ∼500 °C. Epitaxial growth from the crystalline-amorphous boundary, guided by adjacent crystal planes, restores the original diamond structure phase. By 700–800 °C, almost complete recrystallization occurs, maintaining similar interplanar spacing despite residual crystal distortions and dislocations. Notably, heating above 600 °C results in the gradual vanishing of stacking faults, suggesting a dynamic thermal evolution of the crystal defects induced by surface nanoscratching. This work demonstrates thermal annealing as a promising strategy to mitigate nanoscratch-induced defects, paving the way for defect-free-surface of silicon components in ultra-precision machining processes. It offers valuable insights into the interplay between nanoscratching, temperature, and defect evolution, laying the groundwork for surface and subsurface defects elimination in silicon under thermal fields.

The cardiotoxicity caused by Dox chemotherapy represents a significant limitation to its clinical application and is a major cause of late death in patients undergoing chemotherapy. Currently, there are no effective treatments available. Our analysis of 295 clinical samples from 132 chemotherapy patients and 163 individuals undergoing physical examination revealed a strong positive correlation between intestinal barrier injury and the development of cardiotoxicity in chemotherapy patients. We developed a novel orally available and intestinal targeting protein nanodrug by assembling membrane protein Amuc_1100 (obtained from intestinal bacteria Akkermansia muciniphila), fluorinated polyetherimide, and hyaluronic acid. The protein nanodrug demonstrated favorable stability against hydrolysis compared with free Amuc_1100. The in vivo results demonstrated that the protein nanodrug can alleviate Dox-induced cardiac toxicity by improving gut microbiota, increasing the proportion of short-chain fatty acid-producing bacteria from the Lachnospiraceae family, and further enhancing the levels of butyrate and pentanoic acids, ultimately regulating the homeostasis repair of lymphocytes in the spleen and heart. Therefore, we believe that the integrity of the intestinal barrier plays an important role in the development of chemotherapy-induced cardiotoxicity. Protective interventions targeting the intestinal barrier may hold promise as a general clinical treatment regimen for reducing Dox-induced cardiotoxicity.

Effective separation of residual carbon and ash is the basis for the resource utilization of coal gasification fine slag (CGFS). The conventional flotation process of CGFS has the bottlenecks of low carbon recovery and high collector dosage. In order to address these issues, CGFS sample taken from Shaanxi, China was used as the study object in this paper. A new process of size classification − fine grain ultrasonic pretreatment flotation (SC-FGUF) was proposed and its separation effect was compared with that of whole-grain flotation (WGF) as well as size classification − fine grain flotation (SC-FGF). The mechanism of its enhanced separation effect was revealed through flotation kinetic fitting, flotation flow foam layer stability, particle size composition, surface morphology, pore structure, and surface chemical property analysis. The results showed that compared with WGF, pre-classification could reduce the collector dosage by 84.09% and the combination of pre-classification and ultrasonic pretreatment could increase the combustible recovery by 17.29% and up to 93.46%. The SC-FGUF process allows the ineffective adsorption of coarse residual carbon to collector during flotation stage to be reduced by pre-classification, and the tightly embedded state of fine CGFS particles is disrupted and surface oxidizing functional group occupancy was reduced by ultrasonic pretreatment, thus carbon and ash is easier to be separated in the flotation process. In addition, some of the residual carbon particles were broken down to smaller sizes in the ultrasonic pretreatment, which led to an increase in the stability of flotation flow foam layer and a decrease in the probability of detachment of residual carbon particles from the bubbles. Therefore, SC-FGUF could increase the residual carbon recovery and reduce the flotation collector dosage, which is an innovative method for carbon-ash separation of CGFS with good application prospect.

The study of the bedding plane effect has important implications for stability analysis of deep rock masses. However, the differences in shear mechanical behavior between natural layered rocks under reverse and normal dip conditions are still not well understood. For this , a full-angle shear test of shale with 0°≤ψ≤180° (ψ is the bedding plane inclination angle, defined as the angle of clockwise rotation from the shear surface to the laminar surface) was carried out. The shear mechanical properties and differences in failure modes of shale under different bedding plane inclination angles were extensively analyzed. Additionally, the analysis results were supplemented and verified with discrete element simulations. The results are as follows. Firstly, the minimum shear strength is achieved when shearing parallel to the bedding plane. The strength reaches a maximum at ψ=30° and local peaks at 90° and 135°. The shear strength is relatively higher when shearing in the reverse direction. For ψ>30°, the shear strength generally decreases with ψ. Secondly, according to the differences in the shear mechanical behavior under various ψ, the layered rocks are divided into three groups: bedding tension and matrix shear group (ψ=15°-60°), matrix shear group (ψ=75°-120°), matrix and bedding shear group (135°-180°). Thirdly, In the pre-peak stage, stress drop phenomenon only exists in the matrix shear group. In the post-peak stage, stress drops in a “step-like” manner for bedding tension and matrix shear group. Fourthly, tension and shear failures coexist, with shear failure being predominant. Lastly, the number of shear cracks of layer is dominant when shearing parallel to the bedding plane. The number of shear cracks in the matrix is the highest at 90°. At ψ= 30°, the maximum number of tensile cracks is observed in the bedding plane, followed by shear cracks in the matrix. The shear cracks are mainly observed in the bedding and matrix at ψ= 150°. The study reveals the anisotropic characteristics and differences in reverse and normal dip shear of layered rocks. The results provide a scientific basis for improving anisotropic mechanical models and analyzing disaster mechanisms and surrounding rock stability.

Abstract The unsatisfactory insulating properties of solid–gas interfaces seriously restrict the development of high‐voltage electrical equipment and threaten their power supply stability. Electron‐beam irradiation (EBI) can effectively improve the surface flashover voltage of dielectrics. However, the underlying mechanism of EBI in tailoring the surface trap and improving the flashover voltage remains unclear. In this study, the surface morphologies and chemical compositions of epoxy composites treated with EBI were investigated. In addition, the surface wetting properties, surface charge migration parameters, and surface flashover voltages were experimentally characterised. It was found that EBI aggravated the surface morphology, changed the surface chemical components, and repressed surface charge transportation. As a result, the contact angle was reduced from 103.7° to 78.43°, and the flashover voltage in SF6 was increased from 35.26 to 38.90 kV. DFT calculations showed that the newly generated C–O–H and C=O bonds on the surface molecules after EBI formed charge centres at the molecular electrostatic potential, which enhanced the trapping effect of the surface deep trap. As a result, surface charge migration was repressed, and the surface flashover voltage was improved. This study could promote the further development of EBI on materials modification.

This is an article in the field of mineral analysis and testing. A rapid method for the simultaneous determination of Nb, Ta, Li and Be in Nb Ta ore by alkali fusion inductively coupled plasma mass spectrometry was established. The mixed alkali of sodium peroxide and sodium hydroxide=1:1 is used to decompose the sample. During extraction, niobium, tantalum and other elements are completely precipitated and separated from the liquid. The content of niobium, tantalum, lithium and beryllium in the sample is determined by inductively coupled plasma mass spectrometer after conversion and precipitation with 25 mL of 10% sulfuric acid+10% hydrogen peroxide solution. This method is used to determine the national first-class reference materials GBW 07153, GBW 07155 and GBW 07185. The measured values of each element are basically consistent with the certified values, with a relative error of 0.50%～4.77% and a relative standard deviation (n=6) of -0.009%～0.008%. It is applicable to the determination of niobium and tantalum in niobium tantalum concentrates, refractory or complex samples, and has been applied in production practice.

Abstract Objective To investigate the association between meteorological data three days before admission and the status of sputum pathogens culture in hospitalized patients with Acute exacerbation of Chronic obstructive pulmonary disease (AECOPD) and respiratory infections. Methods Data from 1,370 AECOPD patients (80.66% males, approximately 80% age > 70) with respiratory infections hospitalized in Fujian Provincial Hospital between December 2013 and December 2019 were collected. This cohort comprised, along with concurrent meteorological data from Fuzhou. Group differences were analyzed to compare the meteorological data three days prior to admission between patients with positive sputum pathogen cultures and those without. Logistic regression models were employed to investigate the association between meteorological parameters and the status of sputum pathogen cultures in patients with AECOPD and respiratory infections. Sensitivity analyses was conducted among the hospitalized patients from 2013 to 2016 and 2017–2019. Stratified analysis was performed to explore the factors affecting the effect of temperature differences and their interactions. Results 578(42.19%) cases had a positive sputum culture report indicating pathogen growth. 323 cases were found with Gram-negative bacteria, 160 with Gram-positive bacteria, and 114 with fungi. Uni-variate analysis revealed statistical differences in DTD three days prior to admission (DTD-3d) between the positive and negative sputum culture groups (p = 0.019). Multivariate analysis indicated that an increase in the risk of positive sputum pathogen cultures was associated with greater DTD three days before admission (DTD-3d), with OR1.657 (95%CI [ 1.328–1.981]). The risk of positive sputum pathogen cultures was higher in groups with greater DTD-3d. The findings were consistent across different admission periods. Stratified analysis showed that patients without respiratory failure were more affected by DTD-3d, and an interaction effect was observed (p

Abstract Background Rhizoctonia solani is an important plant pathogen worldwide, and causes serious tobacco target spot in tobacco in the last five years. This research studied the biological characteristics of four different anastomosis groups strains (AG-3, AG-5, AG-6, AG-1-IB) of R. solani from tobacco. Using metabolic phenotype technology analyzed the metabolic phenotype differences of these strains. Results The results showed that the suitable temperature for mycelial growth of four anastomosis group strains were from 20 to 30oC, and for sclerotia formation were from 20 to 25oC. Under different lighting conditions, R. solani AG-6 strains produced the most sclerotium, followed by R. solani AG-3, R. solani AG-5 and R. solani AG-1-IB. All strains had strong oligotrophic survivability, and can grow on water agar medium without any nitrutions. They exhibited three types of sclerotia distribution form, including dispersed type (R. solani AG-5 and AG-6), peripheral type (R. solani AG-1-IB), and central type (R. solani AG-3). They all presented different pathogenicities in tobacco leaves, with the most virulent was noted by R. solani AG-6, followed by R. solani AG-5 and AG-1-IB, finally was R. solani AG-3. R. solani AG-1-IB strains firstly present symptom after inoculation. Metabolic fingerprints of four anastomosis groups were different to each other. R. solani AG-3, AG-6, AG-5 and AG-1-IB strains efficiently metabolized 88, 94, 71 and 92 carbon substrates, respectively. Nitrogen substrates of amino acids and peptides were the significant utilization patterns for R. solani AG-3. R. solani AG-3 and AG-6 showed a large range of adaptabilities and were still able to metabolize substrates in the presence of the osmolytes, including up to 8% sodium lactate. Four anastomosis groups all showed active metabolism in environments with pH values from 4 to 6 and exhibited decarboxylase activities. Conclusions The biological characteristics of different anastomosis group strains varies, and there were significant differences in the metabolic phenotype characteristics of different anastomosis group strains towards carbon source, nitrogen source, pH, and osmotic pressure.

Abstract Immunotherapy based on immune checkpoint genes (ICGs) has recently made significant progress in the treatment of bladder cancer patients, but many patients still cannot benefit from it. In the present study, we aimed to perform a comprehensive analysis of ICGs in bladder cancer tissues with the aim of evaluating patient responsiveness to immunotherapy and prognosis. We scored ICGs in each BLCA patient from TCGA and GEO databases by using ssGSEA and selected genes that were significantly associated with ICGs scores by using the WCGNA algorithm. NMF clustering analysis was performed to identify different bladder cancer molecular subtypes based on the expression of ICGs-related genes. Based on the immune related genes differentially expressed among subgroups, we further constructed a novel stratified model containing nine genes by uni-COX regression, LASSO regression, SVM algorithm and multi-COX regression. The model and the nomogram constructed based on the model can accurately predict the prognosis of bladder cancer patients. Besides, the patients classified based on this model have large differences in sensitivity to immunotherapy and chemotherapy, which can provide a reference for individualized treatment of bladder cancer.

The matrix protein 2 (M2) is a preferred target for developing a universal vaccine against the influenza A virus (IAV). This study aimed to develop a method for assessing antibody-dependent cell-mediated cytotoxicity (ADCC) associated with M2-based immunization in mice. We first established a stable cell line derived from mouse lymphoma cells (YAC-1) expressing M2 of H3N2. This cell line, designated as YAC-1-M2, was generated using a second-generation lentiviral tricistronic plasmid system to transduce the M2 gene into YAC-1 cells. The ADCC effect induced by polyclonal antibodies targeting matrix protein 2 ectodomain (M2e) was demonstrated by YAC-1-M2 cell lysis by natural killer cells (NK) derived from mice, in the presence of anti-M2 antibodies obtained from mice immunized with an mRNA vaccine based on M2e. This ADCC effect was found to be stronger compared to the effect induced by monoclonal antibodies (14C2) against M2. Moreover, the ADCC effect was enhanced as the effector-to-target ratio of NK to YAC-1-M2 cells increased. In conclusion, we established a novel method to detect ADCC of M2 of IAV, which paves the way for the development of an M2-based universal vaccine against IAV and an in-depth analysis of its mechanism of broad-spectrum immune protection in mice.

Abstract We theoretically investigate the model of a quadratically coupled optomechanical system with a Newtonian gravitational potential in the weak-driving regime, where the optical cavity is driven by an external laser. The steady state of the whole system is treated in the framework of a few-photon subspace. We find that the conventional single-photon blockade, nonstandard types of single-photon blockade, two-photon blockade, and photon-induced tunneling can be induced by gravity when the quadratic optomechanical coupling strength remains constant. Moreover, we find that gravitational potential energy can compensate for the lack of quadratic optomechanical coupling for observation photon blockade. In particular, the photon stream with super-Poissonian distribution can be converted into a sub-Poissonian, antibunching photon stream by changing the driving detuning when the gravitational potential energy is included. These results show that the gravity has potential for realizing the manipulation of photon blockade in a quadratically coupled optomechanical system.

Abstract As data and protocols are increasingly generated, accessed, and manipulated electronically, many labs are shifting to storing data in electronic laboratory notebooks (ELNs). ELNs provide clear advantages in readability, shareability, searchability, accessibility, and data security over their paper counterparts. Our interdisciplinary program implemented ELNs across several sections of our gateway molecular biology laboratory course and analyzed the impact on 384 students (13 sections total from Fall 2016 to Spring 2018) using surveys, focus groups, and grade data. We found that students prefer the electronic format, citing the ease of transitioning to lab reports and the longevity of their data. Course grades overall were not affected by the change. Based on our experience, we offer suggestions for smoothing the transition to an ELN system in undergraduate and graduate laboratory courses, including use during remote teaching.

Abstract Orogenic curvatures have been widely recognized along global convergent plate boundaries. Understanding the impact of such curvatures on the tectonic evolution of orogens and their three-dimensional architecture has been challenging. Here we address this issue by studying magmatism around the tightly curved Mongolian Orocline in Central Asia. Our results show that during the Permian–Triassic, arc magmatism around the inner hinge of the orocline became younger towards the core of the orocline. During the same period, the crust was thickened, as indicated by Lanthanum-Ytterbium ratio proxy. These findings, together with the observation that the present-day hinge zone of the Mongolian Orocline is wider, indicate that this zone was subjected to significant crustal-scale contraction. This contractional deformation accounts for the relatively thicker crust around the inner hinge of the Mongolian Orocline, and offers a novel perspective on the formation of elevated topography around the hinge of curved plate boundaries.

Abstract Coupling carbon capture with electrocatalytic carbon dioxide reduction (CO2R) to yield high‐value chemicals presents an appealing avenue for combating climate change, yet achieving highly selective electrocatalysts remains a significant challenge. Herein, two molecularly woven covalent organic frameworks (COFs) are designed, namely CuCOF and CuCOF+, with copper(I)‐bisphenanthroline complexes as building blocks. The metal–organic helical structure unit made the CuCOF and CuCOF+ present woven patterns, and their ordered pore structures and cationic properties enhanced their CO2 adsorption and good conductivity, which is confirmed by gas adsorption and electrochemical analysis. In the electrocatalytic CO2R measurements, CuCOF+ decorated with extra ethyl groups exhibit a main CO product with selectivity of 57.81%, outperforming the CuCOF with 42.92% CO at the same applied potential of 0.8 VRHE. After loading Pd nanoparticles, CuCOF‐Pd and CuCOF+‐Pd performed increased CO selectivity up to 84.97% and 95.45%, respectively. Combining the DFT theoretical calculations and experimental measurements, it is assumed that the molecularly woven cationic COF provides a catalytic microenvironment for CO2R and ensures efficient charge transfer from the electrode to the catalytic center, thereby achieving high electrocatalytic activity and selectivity. The present work significantly advances the practice of cationic COFs in real‐time CO2 capture and highly selective conversion to value‐added chemicals.

Background Russian wildrye (RWR, Psathyrostachys juncea) is an outcrossing perennial grass that plays a crucial role in foragaing and rangeland restoration due to its tiller producing capabilities, nevertheless, a genetic map has yet to be constructed due to a shortage of efficient and reliable molecular markers. This also limits the identification, localization, and cloning of economically important traits related to tiller density during breeding. Methods Therefore, this study aimed to create a F1 mapping population with 147 individual lines and their two parents, which were selected based on varying tiller densities. We then used this mapping population to conduct specific-locus amplified fragment sequencing (SLAF-seq) to generate SLAF markers and discover single nucleotide polymorphisms (SNPs). Results Initially, we generated a total of 1,438.38 million pair-end reads with an average sequencing depth of 84.92 in the maternal line, 79.34 in the parental line, and 27.05 in each F1 individual line, respectively. Following the filtering of low-depth SLAF tags, a total of 558,344 high-quality SLAFs were identified. A total of 1,519,903 SNP markers were obtained, and 62,424 polymorphic SNPs were discovered. From these, 4,644 polymorphic SNPs were selected and used for the construction of a genetic map encompassing seven linkage groups. The genetic map spanned 1,416.60 cM with an average distance of 0.31 cM between adjacent markers. Comparative analysis between the seven linkage groups of RWR SLAF tag and the whole-genome sequences in barley (Hordeum vulgare L.) revealed homology values ranging from 17.5% to 34.6%, and the collinearity between the RWR linkage groups and the barley homology groups ranged from 0.6787 to 0.9234, with an average value of 0.8158. Additionally, 143 significant quantitative trait locus (QTLs) with Logarithm of Odds (LOD) value greater than 2.5 for five tiller related traits were detected using three consecutive years of phenotypic trait data from the F1 population, further verifying the map’s reliability.

Seasonal polyphenism enables organisms to adapt to environmental challenges by increasing phenotypic diversity. Cacopsylla chinensis exhibits remarkable seasonal polyphenism, specifically in the form of summer-form and winter-form, which have distinct morphological phenotypes. Previous research has shown that low temperature and the temperature receptor CcTRPM regulate the transition from summer-form to winter-form in C. chinensis by impacting cuticle content and thickness. However, the underling neuroendocrine regulatory mechanism remains largely unknown. Bursicon, also known as the tanning hormone, is responsible for the hardening and darkening of the insect cuticle. In this study, we report for the first time on the novel function of Bursicon and its receptor in the transition from summer-form to winter-form in C. chinensis. Firstly, we identified CcBurs-α and CcBurs-β as two typical subunits of Bursicon in C. chinensis, which were regulated by low temperature (10 °C) and CcTRPM. Subsequently, CcBurs-α and CcBurs-β formed a heterodimer that mediated the transition from summer-form to winter-form by influencing the cuticle chitin contents and cuticle thickness. Furthermore, we demonstrated that CcBurs-R acts as the Bursicon receptor and plays a critical role in the up-stream signaling of the chitin biosynthesis pathway, regulating the transition from summer-form to winter-form. Finally, we discovered that miR-6012 directly targets CcBurs-R, contributing to the regulation of Bursicon signaling in the seasonal polyphenism of C. chinensis. In summary, these findings reveal the novel function of the neuroendocrine regulatory mechanism underlying seasonal polyphenism and provide critical insights into the insect Bursicon and its receptor.

BackgroundTo investigate microbial characteristics across multibody sites from chronic pancreatitis (CP), through pancreatic benign tumors, to pancreatic ductal adenocarcinoma (PDAC) at different stages.Methods16S ribosomal RNA (rRNA) amplicon sequencing was conducted on saliva, duodenal fluid, and pancreatic tissue obtained via endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of patients with CP, pancreatic benign tumors, PDAC in stage I/II, III, and IV. The neutral community model (NCM) assessed the microbial assembly contribution and MaAslin2 identified the differential microbes.ResultsFrom CP to stage IV PDAC patients, there was a marked surge in influence of salivary and duodenal microbiota on constitution of pancreatic microbial communities. Our observations revealed a successive alteration in microbial species across various bodily sites during PDAC tumorigenesis. Notably, Porphyromonas gingivalis, Treponema denticola, Peptoanaerobacter stomatis, Propionibacterium acidifaciens, Porphyromonas endodontalis, Filifactor alocis, etc., sequentially increased along PDAC progression in pancreatic tissue, whereas bacteria commonly used as probiotics Bifidobacterium breve, Lactiplantibacillus plantarum, etc., declined. Furthermore, the sequentially escalating trends of Peptoanaerobacter stomatis and Propionibacterium acidifaciens during PDAC tumorigenesis were mirrored in duodenal fluid and saliva. Porphyromonas gingivalis, Porphyromonas endodontalis, and Filifactor alocis, which intensified from CP to stage IV PDAC in pancreatic tissue, were also found to be enriched in saliva of patients with short-term survival (STS) compared with those with long-term survival (LTS).ConclusionsSalivary and duodenal microorganisms were prominent factors in shaping pancreatic microbial landscape in PDAC context. Further exploration of these microbial entities is imperative to unravel their specific roles in PDAC pathogenesis, potentially yielding insights for future therapeutic strategies.

Cervical cancer is a common malignant tumor of female reproductive system. Radiation therapy is one of the main methods of cervical cancer treatment, of which brachytherapy is an essential and important part of radiation therapy for locally advanced cervical cancer. With the rapid development of imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI), brachytherapy for cervical cancer has gradually developed from traditional two-dimensional image-guided technology to three-dimensional image-guided technology. And there are more and more treatment methods, including intracavitary brachytherapy, interstitial brachytherapy, and intracavitary combined interstitial implantation brachytherapy. We performed a PubMed search for introduce the application progress of intracavity, implantation, intracavity combined implantation brachytherapy and radioactive seed implantation, and discuss the dosimetric feasibility of internal and external fusion irradiation.

Abstract Obstructive sleep apnea (OSA) is a common sleep disorder characterized by intermittent hypoxia (IH) and is associated with the occurrence and development of nonalcoholic fatty liver disease (NAFLD). However, the specific mechanism by which OSA induces NAFLD remains unclear. Therefore, effective interventions are lacking. This study aims to investigate the role and mechanism of ferroptosis in OSA‐related NAFLD using clinical data analyses, cell‐based molecular experiments, and animal experiments. Indicators of liver function, lipid accumulation, and ferroptosis are also examined. RNA‐seq, qPCR, western blotting, gene intervention, and E3 ligase prediction using UbiBrowser and co‐IP are used to explore the potential underlying mechanisms. The results show that ferroptosis increases in the liver tissues of patients with OSA. Chronic IH promotes NAFLD progression in mice and is alleviated by a ferroptosis inhibitor Fer‐1. The increased secretion of IL6 by macrophages can promote the expression of MARCH3 in hepatocytes under intermittent conditions, and subsequently promote the ubiquitination and degradation of GPX4 to regulate ferroptosis and lipid accumulation in hepatocytes. Hence, targeted inhibition of MARCH3 may alleviate IH‐induced ferroptosis and lipid accumulation in liver tissues and inhibit the progression of NAFLD.

The Ms 5.5 earthquake struck on 24 October 2023, in Subei County, Gansu Province, China, occurring along the eastern segment of the Altyn Tagh fault. It raises the question of whether this earthquake is linked to the ongoing shortening slip rate along this segment or triggered by other seismic events. Analyzing the fault geometry of the Subei earthquake and understanding the significance of the weakening activity rate for seismic hazards in neighboring regions is crucial. The surface deformation from small- and medium-sized earthquakes (magnitudes less than Mw5.5) is often subtle, and the coseismic deformation detected by interferometric synthetic aperture radar (InSAR) is vulnerable to atmospheric disturbances, leading to significant measurement errors. Moreover, inaccuracies in the regional crustal velocity structure can cause errors in earthquake localization based on seismic data. These challenges complicate the establishment of a rupture model for seismogenic faults and hinder the inversion of fault slip models. To overcome these limitations, we employed the time-series InSAR stacking method and aftershock relocation to determine the fault geometry of the Subei earthquake. A two-step inversion method was utilized to ascertain both the fault geometry and slip distribution. Our modeling indicates that the 2023 Subei earthquake had a thrust mechanism with a component of strike-slip. The rupture did not reach the surface, with the maximum fault slip measuring 0.45 m at a depth of 2.5–3.5 km. The fault dips westward, and the moment magnitude is calculated at 5.4. This earthquake is associated with the ongoing weakening of the left-lateral strike-slip rupture along the Altyn Tagh fault in the Subei region. Furthermore, retrograde thrust tectonics significantly contribute to the absorption of accumulated stress during this process.Our findings highlight the potential of utilizing time-series InSAR images to enhance earthquake catalogs with geodetic observations, offering valuable data for further studies of the earthquake cycle and active tectonics. This approach is also applicable in other tectonically active regions, enhancing understanding of seismic hazards and risk assessment.

ObjectiveOur study was conducted to explore the link between oxidative balance score (OBS) and rheumatoid arthritis (RA).MethodsA total of 21,415 participants were included in our research from five cycles (2011–2012, 2013–2014, 2015–2016, 2017–2018, and 2017–2020) of the National Health and Nutrition Examination Survey (NHANES). Moreover, 20 elements related to diet as well as lifestyle were combined to calculate OBS. The relationship between OBS and RA was assessed by employing multivariable regression analysis, and further exploration was carried out through subgroup analysis, restricted cubic spline analysis, and sensitivity analysis. Multiple covariates were selected to adjust the model for more robust results.ResultsIn our cross-sectional study, a higher OBS has a protective effect on the development of RA (OR = 0.98, 95% CI: 0.97 to 0.99). In contrast to individuals aged ≥60, the result is more prominent in the population aged 20–60 (OR = 0.97, 95% CI: 0.96 to 0.98). Marital status appears to introduce interference in the relationship between OBS and RA, and unmarried individuals exhibited different outcomes (OR = 1.02, 95% CI: 0.99 to 1.04) compared to others. The positive influence of OBS was more evident in patients with chronic kidney disease and cardiovascular disease, while it was stronger in individuals without diabetes and liver disease.ConclusionA higher OBS correlates with a reduced odd of RA. Further studies are needed to shoot more sights on improving dietary habits and lifestyles to gain proper OBS and explore whether OBS can be one of the measurements utilized to measure the risk of RA.

Ecological engineering of Fe-ore tailings into Technosols (or soil-like growth media) offers a promising way to rehabilitate tailings without resorting to natural topsoil from other places. Among key pedogenic processes, soil aggregate formation and organic matter (OM) stabilisation are critical to the development of sustainable Technosols. The colonisation of pioneer plant species highly adaptive to infertile soils and water deficit may act as competent biological drivers to enhance these critical processes involved in Technosol formation. This study aimed to investigate the role of an Australian native plant species, Acacia auriculiformis, in enhancing water-stable aggregate formation and associated OM stabilisation using a pot experiment under glasshouse conditions. The influences of two relevant abiotic processes, including water deficit and phosphorus deficiency, on these key processes were evaluated. A. auriculiformis colonisation enhanced the formation of water-stable aggregates in the early Technosols, while the proportion of macroaggregates and microaggregates were altered differently, with the former increasing under well-watered conditions and the latter increasing under water deficit conditions. A. auriculiformis colonisation increased N-rich mineral-associated OM within the macroaggregates. In aggregates, OM stabilisation was related to interactions of carboxyl-rich organic groups with tailing minerals. The influences of water deficit and phosphorus deficiency on aggregate formation and OM stabilisation were mediated via their impacts on the growth and root functions of A. auriculiformis, including root extension, entanglement, and exudation. From these findings, the utilisation of A. auriculiformis is recommended as a biological driver to facilitate the development of early Technosols from eco-engineered Fe-ore tailings.