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Background: Anhedonia is a deficit of dynamic reward process, and a large proportion of schizophrenia patients continue to experience anhedonia even during the stable phase. However, few studies have examined the multiple aspects of performance in reward processing in patients with stable schizophrenia and evidence suggests that physical and cognitive effort may involve different neural mechanisms. Methods: Parallel measures of effort-based expenditure for reward tasks (EEfRT) and self-report questionnaires of pleasure were applied in 61 patients with stable schizophrenia (SSZ) and 46 healthy controls (HCs), and percentages of hard task choices (HTC%) were used to assess motivation in reward processing. Negative symptoms, neurocognitive and social function were evaluated in SSZ patients, and associations with performance in reward tasks were explored. Results: SSZ patients reported more severe consummatory and anticipatory anhedonia and social anhedonia. HTC% in reward tasks of SSZ patients were significantly lower than that of HCs, especially in cognitive-effort tasks. HTC% in cognitive tasks were correlated with motivation and pleasure dimension of negative symptoms, whereas HTC% in physical tasks were associated with expression dimension. Anticipatory anhedonia and negative symptoms were correlated with Personal and Social Performance Scale (PSP) scores. Conclusion: Patients with stable schizophrenia have social anhedonia, physically consummatory and anticipatory anhedonia and reduced reward motivation. They are less willing to make cognitive effort than physical effort for reward. The different associations of physical and cognitive effort with negative symptoms indicate physical and cognitive effort may represent disparate neuropsychological processes. Anticipatory anhedonia is closely related to social functioning.

The variance in molecular weight stands as the principal reason behind the compromised compatibility within modified asphalt systems. In order to improve the compatibility of modified asphalt, this study integrates the concept of molecular weight gradient design, while considering a balance of performance. Composite modified asphalt samples were prepared using preferred Styrene-Butadiene-Styrene (SBS), Styrene-Butadiene Rubber (SBR), and Butyl Rubber (BR) for comprehensive assessments, including molecular weight distribution, conventional and rheological properties, thermal stability, microstructural morphology, and functional group transformations, and subsequently elucidate the underlying modification mechanisms. The results show that the molecular weight gradient-designed composite modified asphalt exhibits good performance and enhanced compatibility. On the one hand, the styrene and butadiene segments can improve the high and low-temperature performance of the asphalt, respectively. On the other hand, as the molecular weight within the system diminishes, the consistence and hardness of the asphalt decrease, the cross-linking network goes denser, improving compatibility and stability. Moreover, the addition of stabilizer can change the micro-cross-linking network structure and induce functional group transformations of the composite modified asphalt, which conforms to the characteristics of chemical modification.

Background: Perioperative heparin-free anticoagulation extracorporeal membrane oxygenation (ECMO) for lung transplantation is rarely reported. Objective: To evaluate the impact of a heparin-free strategy on bleeding and thrombotic events, blood transfusion, and coagulation function during the early perioperative period and on prognosis, and to observe its effect on different ECMO types. Design: A retrospective cohort study. Methods: Data were collected from 324 lung transplantation patients undergoing early perioperative heparin-free ECMO between August 2017 and July 2022. Clinical data including perioperative bleeding and thrombotic events, blood product transfusion, coagulation indicators and 1-year survival were analysed. Results: Patients were divided in venovenous (VV; n = 251), venoarterial (VA; n = 40) and venovenous-arterial (VV-A; n = 33) groups. The VV group had the lowest intraoperative bleeding and thoracic drainage within 24 h postoperatively. Vein thrombosis occurred in 30.2% of patients within 10 days postoperatively or 1 week after ECMO withdrawal, and no significant difference was found among the three groups. Double lung transplantation, increased intraoperative bleeding, and increased postoperative drainage were associated with vein thrombosis. Except for acute myocardial infarction in one patient, no other serious thrombotic events occurred. The VV-ECMO group had the lowest demand for blood transfusion. The highest prothrombin time and the lowest fibrinogen levels were observed in the VA group during ECMO run, while the highest platelet counts were found in the VV group. Both intraoperative bleeding and thoracic drainage within 24 h postoperatively were independent predictors for 1-year survival, and no thrombosis-related deaths occurred. Conclusion: Short-term heparin-free anticoagulation, particularly VV-ECMO, did not result in serious thrombotic events or thrombosis-related deaths, indicating that it is a safe and feasible strategy for perioperative ECMO in lung transplantation.

A 2 × 2 factorial experiment (protein levels, 40 %, and 45 %; lipid levels, 5 %, and 7 %) was conducted to explore the influences of dietary protein and lipid levels on growth performance, digestive and absorptive capacities, and potential signaling molecules of Sinilabeo rendahli (initial weight, 66.19 ± 0.28 g). The formulated diets were named as group 1 (40/5), group 2 (45/5), group 3 (40/7) and group 4 (45/7) (protein/lipid, %), respectively. After an 8-week feeding trial, four diets had no significant effect on the final body weight, percentage of weight gain, and specific growth rate of S. rendahli. However, the group 2 (45/5) showed the lowest feed intake and an increase in feed efficiency of 17.71–34.38 % compared to the other groups. Furthermore, the group with 45 % protein had a higher protein production value compared to the group with 40 % protein, while the highest values for lipid production and ash production were observed in group 2 (45/5). Additionally, protein and lipid digestive and brush border enzyme activities, as well as p-TOR and p-S6k1/S6K1 protein levels were improved in group 2 (45/5), whereas p-4EBP1 was decreased. Meanwhile, the intestinal morphological structure (muscular layer, intestinal folds, and goblet cells) was enhanced in group 2 (45/5). This could be associated with elevated levels of tight junction proteins, including zonula occluden-1, occludin, and claudin-3. Overall, the group 2 (45/5) enhanced the digestive and absorptive capacities through increasing protein and lipid digestive and absorptive enzyme activities, improving intestinal morphology, and higher levels of tight junction proteins in S. rendahli. This suggested that a diet consisting of 45 % protein and 5 % lipid is suitable for S. rendahli.

Nanozymes, a category of nanomaterials endowed with enzyme-mimicking capabilities, have exhibited considerable potential across diverse application domains. This comprehensive review delves into the intricacies of regulating nanozymes through N elements, elucidating the mechanisms governing N element control in the design and application of these nanomaterials. The initial sections introduce the foundational background and significance of nanozymes. Subsequent exploration delves into the detailed discussion of N element regulation mechanisms on nanozymes, encompassing N vacancies, N doping, N coordination, and nitride. These regulatory pathways play an instrumental role in fine-tuning the catalytic activity and specificity of nanozymes. The review further scrutinizes practical applications of N element regulation on nanozymes, spanning sensing detection, infection therapy, tumor therapy, and pollutant degradation. In conclusion, it succinctly summarizes the current research findings and proposes future directions for development. This thorough investigation into the regulation of nanozymes by N elements anticipates precise control over their performance, thereby advancing the extensive utilization of nanozymes in the realms of biomedical and environmental applications.

Severe brain injury impairs consciousness by disrupting a broad spectrum of neurotransmitter systems. Emerging evidence suggests that pharmacologic modulation of specific neurotransmitter systems, such as dopamine, promotes recovery of consciousness. Clinical guidelines now endorse the use of amantadine in individuals with traumatic disorders of consciousness (DoC) based on level 1 evidence, and multiple neurostimulants are used off-label in clinical practice, including methylphenidate, modafinil, bromocriptine, levodopa, and zolpidem. However, the relative contributions of monoaminergic, glutamatergic, cholinergic, GABAergic, and orexinergic neurotransmitter systems to recovery of consciousness after severe brain injury are unknown, and personalized approaches to targeted therapy have yet to be developed. This review summarizes the state-of-the-science in the neurochemistry and neurobiology of neurotransmitter systems involved in conscious behaviors, followed by a discussion of how pharmacologic therapies may be used to modulate these neurotransmitter systems and promote recovery of consciousness. We consider pharmacologic modulation of consciousness at the synapse, circuit, and network levels, with a focus on the mesocircuit model that has been proposed to explain the consciousness-promoting effects of various monoaminergic, glutamatergic, and paradoxically, GABAergic therapies. Though fundamental questions remain about neurotransmitter mechanisms, target engagement and optimal therapy selection for individual patients, we propose that pharmacologic therapies hold great promise to promote recovery and improve quality of life for patients with severe brain injuries.

Background Acute venous thromboembolism (VTE) in children presents unique challenges due to the limitations of standard anticoagulation therapies. Herein, we aimed to systematically review randomized controlled trials (RCTs) evaluating the efficacy and safety of direct oral anticoagulants (DOACs) in pediatric patients with acute VTE. Methods PubMed and Embase databases were searched for RCTs comparing DOACs to standard anticoagulation in pediatric VTE patients. Efficacy outcomes included VTE recurrence and all-cause mortality, while safety outcomes comprised major bleeding and other adverse events. Results Three RCTs with 790 participants were included. When compared with standard anticoagulation, DOACs demonstrated a reduced risk of VTE recurrence (risk difference[RD] = −3%, 95% confidence interval[CI]: −6% to 0%, P = 0.04) and an increased risk of any adverse event (RD = 8%, 95% CI: 1% to 14%, P = 0.02). No significant differences were found in all-cause mortality, major bleeding, clinically relevant non-major bleeding, or total bleeding between the DOAC and control groups. Conclusion DOACs, primarily dabigatran and rivaroxaban, are non-inferior to standard anticoagulants in reducing VTE recurrence in pediatric patients, with comparable safety profiles. Further research is essential to confirm these findings.

Abstract High‐field preclinical functional MRI (fMRI) is enabled the high spatial resolution mapping of vessel‐specific hemodynamic responses, that is single‐vessel fMRI. In contrast to investigating the neuronal sources of the fMRI signal, single‐vessel fMRI focuses on elucidating its vascular origin, which can be readily implemented to identify vascular changes relevant to vascular dementia or cognitive impairment. However, the limited spatial and temporal resolution of fMRI is hindered hemodynamic mapping of intracortical microvessels. Here, the radial encoding MRI scheme is implemented to measure BOLD signals of individual vessels penetrating the rat somatosensory cortex. Radial encoding MRI is employed to map cortical activation with a focal field of view (FOV), allowing vessel‐specific functional mapping with 50 × 50 µm2 in‐plane resolution at a 1 to 2 Hz sampling rate. Besides detecting refined hemodynamic responses of intracortical micro‐venules, the radial encoding‐based single‐vessel fMRI enables the distinction of fMRI signals from vessel and peri‐vessel voxels due to the different contribution of intravascular and extravascular effects.

Summary: Background: Acute coronary syndrome (ACS) often co-occurs with depression, which adversely affects prognosis and increases medical costs, but effective treatment models are lacking, particularly in low-resource settings. This study aims to determine the effectiveness of an ACS and depression integrative care (IC) model compared to usual care (UC) in improving depression symptoms and other health outcomes among patients discharged for ACS in Chinese rural hospitals. Methods: A multicentre, randomised controlled trial was conducted in sixteen rural county hospitals in China, from October 2014 to March 2017, to recruit consecutively all ACS patients aged 21 years and older after the disease stablised and before discharge. Patients were randomly assigned in a 1:1 ratio to receive either the IC or UC, stratified by hospital and depression severity. Patients allocated to IC received an ACS secondary prevention program and depression care including case screening, group counselling, and individual problem-solving therapy. Patients allocated to UC received usual care. The primary outcome was change in Patient Health Questionnaire-9 (PHQ-9) from baseline to 6 and 12 months. Main secondary outcomes included major adverse events (MAEs) composed of all-cause death, non-fatal myocardial infarction and stroke, and all-cause re-hospitalisation. Participants were followed up till March 2018. All data were collected in person by trained assessors blinded to treatment group and MAEs were adjudicated centrally. This trial is registered with ClinicalTrials.gov, NCT02195193. Findings: Among 4041 eligible patients (IC: 2051; UC: 1990), the mean age was 61 ± 10 years and 63% were men. The mean PHQ-9 score lowered at both 6 and 12 months in both groups but was not lower in IC compared to UC at 6 months (mean difference (MD): −0.04, 95% confidence interval (CI): −0.20, 0.11) or 12 months (MD: −0.06, 95% CI: −0.21, 0.09). There were no treatment group differences for MAEs or other secondary outcomes except for secondary prevention medications at 12 months (45.2% in IC vs 40.8% in UC; relative risk: 1.21, 95% CI: 1.05–1.40). Pre-specified subgroup analyses showed that IC, compared to UC, may be more effective in lowering PHQ-9 scores in women, older patients, and patients with low social support, but less effective in moderately and severely depressed patients (all p for interaction

In order to improve the mechanical properties of backfill, steel slag and straw fiber were used as materials to prepare backfill. The law of sand-cement ratio, mass concentration, steel slag content and straw fiber on strength and rheological parameters of backfill was analyzed by orthogonal test method, and the influence mechanism of steel slag content and straw fiber on physical properties of backfill was revealed. The results show that mass concentration exerts the most substantial impact on rheological parameters, emerging as a significant determinant. Moreover, the yield stress diminishes with escalating tailings-cement ratio, while it escalates with higher mass concentration, steel slag content and straw fiber content. Augmenting the tailings-cement ratio and steel slag content serves to impede the amplification effect of mass concentration on yield stress. Notably, the tailings-cement ratio emerges as the most influential factor affecting the uniaxial compressive strength (UCS) of the backfill, albeit the UCS diminishes with rising tailings-cement ratio. Elevating the mass concentration and steel slag content can counteract the debilitation caused by an increase in the tailings-cement ratio on the UCS of the backfill. Furthermore, heightened mass concentration can bolster the reinforcing impact of steel slag content on early UCS. The increase of tailings-cement ratio increases the size and range of the void inside the backfill, subsequently leading to the degradation of its macroscopic compressive strength. The adhesion between straw fiber and mortar matrix constitutes a pivotal factor in improving the integration of backfill, whereas steel slag contributes to improving the mechanical properties by enhancing the distribution of void structures within the backfill. This research not only offer data support and scientific guidance for the design of backfill ratio parameters but also facilitate the broader application of straw fiber and steel slag in mine backfilling operations.

Abstract Objectives HER2 is an infrequently mutated driver gene in non‐small cell lung cancer (NSCLC). At present, there has been no comprehensive large‐scale clinical study to establish the optimal first‐line treatment strategy for advanced lung adenocarcinoma (LUAD) with HER2‐Mutant. Besides that, the effectiveness and safety of pyrotinib, a pan‐HER inhibitor, in the context of NSCLC are still undergoing investigation. Materials and Methods In this study, we conducted a retrospective data collection of HER2‐Mutated advanced LUAD who received first‐line treatment and pyrotinib between May 2014 and June 2023. Patients treated with chemotherapy, chemotherapy + immune checkpoint inhibitors (ICIs), chemotherapy + bevacizumab and pyrotinib in first‐line treatment. Furthermore, we collected data on the efficacy and safety of pyrotinib in these patients after disease progression. The main endpoint of the study was progression‐free survival (PFS). Results In the final analysis, 89 patients were included in the first‐line cohort and 30 patients were included in the pyrotinib cohort. In the first‐line treatment cohort, chemotherapy + ICIs, chemotherapy + bevacizumab, and pyrotinib exhibited notable survival benefits compared to chemotherapy (median PFS: 9.87 vs. 7.77 vs. 7.10 vs. 5.40 months, p‐value

Objective This study aimed to assess the accuracy of Mac-2 binding protein glycosylation isomer (M2BPGi) in predicting the stage of liver fibrosis. Methods Articles published until October 10, 2023, were searched in the PubMed, Embase, Web of Science, and Cochrane Library databases. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), summary receiver–operator curves (SROC), and Spearman’s rank correlation coefficient were used to examine the accuracy of M2BPGi in predicting the stage of liver fibrosis. A 95% confidence interval (CI) was provided for each estimate. Results Twenty-four studies were included in this meta-analysis, including 3,839 patients with liver fibrosis, 409 of whom progressed to stage 4 or above. The pooled sensitivity, specificity, and area under the ROC (AUC) for M2BPGi predicting liver fibrosis ≥F3 were 0.74 (95% CI [0.65–0.82]), 0.84 (95% CI [0.76–0.89]), and 14.99 (95% CI [9.28–24.21]), respectively. The pooled sensitivity, specificity, and AUC for ≥F4 were 0.80 (95% CI [0.70–0.88]), 0.80 (95% CI [0.73–0.86]), and 16.43 (95% CI [0.84–0.90]), respectively. Conclusion Among different sample partitions, M2BPGi has the best diagnostic performance for liver fibrosis stage ≥4. Furthermore, the cutoff of 1–2 is more accurate than that of 0–1 or 2–3 for fibrosis ≥ F3 and ≥ F4. Registration CRD42023483260.

Males display phenotypic characteristics that may be associated with their quality, allowing non-random mating and post-copulatory female choice. In the damselfly Calopteryx haemorrhoidalis asturica, males have a conspicuous pink colouration in the underside of abdominal segments 8–10, which they exhibit during pre- and post-copulatory courtship. We hypothesized that this colouration functions to increase male mating success and/or to elicit females to oviposit. We estimated mating and oviposition success of 27 males, and on the following day, treated males had their segments 8–10 painted black and control males the seventh segment. We recorded the number of male–male fights and courtships, whether the courtship ended in copulation, and whether the female remained in the territory and laid eggs. Our results indicate that the mating success of male C. h. asturica was not significantly affected by the removal of the pink colouration of the abdominal tip, but this colouration clearly affected their success in enticing females to oviposit. Courtship frequency, fat content and muscle mass were positively correlated to male mating rate, and the number of aggressive encounters was negatively correlated. Our study yields experimental evidence for the function of pink colouration of male C. h. asturica, in the context of post-copulatory sexual selection.

Abstract Indole‐3‐acetic acid (IAA) assumes a pivotal role as a phytohormone of utmost importance, intricately orchestrating the nuanced processes associated with the growth and developmental trajectories of botanical organisms. In this study, we have designed and fabricated a label‐free electrochemical impedance immunosensor for the precise detection of IAA. The detection strategy predominantly relied upon polydopamine modified carbon nitride (C3N4) nanosheets (PCN) and polyamidoamine (PAMAM) dendrimer. Through the modification with PCN and PAMAM, the electrode has increased the active area and enhanced the immobilization capacity of antibodies for IAA. The immunosensor‘s ability to capture IAA was significantly improved by enhancing the immunoreaction between the antibody and antigen. This enhancement led to an increased response in the electrochemical behavior of the Fe(CN)63−/4− redox probe. The impedance immunosensor developed exhibits remarkable sensitivity, exceptional selectivity, and consistent performance in the detection of IAA. This assay method, with the potential to replace antibodies, could offer an alternative approach for detecting various phytohormones.

Background: Traditional working procedures requires a lot of clinical processes and processing time. Methods: The orthodontic metal appliances were made by applying oral scanners, digital images, computer-aided design and computer-aided manufacturing (CAD-CAM) printers. Results: The computer digital technology simplified the manufacturing process for dental appliances and shorten the duration for clinical operation and technical processing. Conclusions: The technique described in this paper can guarantee the accuracy of orthodontic appliances and bring revolution the field. Clinical significance: The CAD-CAM technology provides a fully digital workflow for manufacturing metal orthodontic appliances, which saves a considerable amount of labor and material costs, and significantly reduces heavy metal pollution in the working environment of dental technicians.

At present, the technology of artificial intelligence has been developing, making people's life more convenient and production more efficient. As the artificial intelligence software Siri is accepted and used by more and more people, some voice assistant software with similar functions gradually appear in people's vision, such as Sogou voice assistant, Xiaoai, Xiaodu and so on. ASR is the entrance of Siri and other software systems. The quality of software is directly affected by ASR. If there is no good ASR, it is impossible to have high-quality voice assistant applications. Therefore, we must correctly understand the important value of ASR and deeply study this technology in order to achieve better human-computer interaction. In recent years, the development of communication network technology is changing rapidly, from 2G to 5G, technology has been in progress. Compared with the previous 4G, 5G has a higher technical level, whether in network equipment or in data computing technology. For 5 g network, cloud computing technology is very important and has a great impact on it, so we need to focus on the research to realize the optimization and innovation development of 5G network. The construction sector constitutes a crucial segment of China's economy, exerting a significant influence on its overall growth trajectory. Given the prevailing developmental context, this document provides a concise overview of the BIM (Building Information Modeling) Technology, encompassing its fundamental concept, distinguishing attributes, and core principles. Furthermore, it delves into the manifold junctures where BIM Technology finds application across the entire construction life cycle. By employing an actual project as an illustrative instance, this study compiles a synopsis of BIM Technology's utilization at each phase, conducting a comprehensive evaluation of the project through the lens of the accrued experience and outcomes. This assessment lays the groundwork for an extensive exploration of potential expansion and application avenues, culminating in the eventual advancement of BIM Technology's achievements.

Abstract Objective To observe the effect of the whole-process care model of the medical union on the improvement of kinesiophobia and bone mineral density in patients with osteoporosis. Methods In this descriptive study, a convenient sampling method was used to select 148 patients with osteoporosis who visited the hospital from January 2020 to December 2021. Patients aged ≥ 18 years and diagnosed with osteoporosis through quantitative computed tomography (QCT) were included in the study. They were able to cooperate during follow-up and had normal cognitive function. Patients with combined spinal curvature, thoracic deformity, and pulmonary dysfunction, accompanied by severe cardiovascular or limb dysfunction, and those who withdrew midway or participated in other clinical studies were excluded. According to whether to use the whole-process care model of the medical union, they were divided into intervention group and control group, with 74 cases each. The control group used conventional care, and the intervention group used the whole-process care model of the medical association. The occurrence of kinesiophobia between the two groups were compared. The dual-energy X-ray absorption detector is used to measure differences in bone density changes. Results There was no significant difference between the two groups in the TSK scale score and the incidence of kinesiophobia before intervention (P > 0.05). The TSK scale scores of patients in the intervention group were higher than those in the control group at 3 months and 6 months after operation (P 0.05). The bone mineral density of lumbar spine, femoral neck and total hip in the intervention group was significantly higher than that in the control group after 6 months of intervention (P

Abstract In this note, we study some approximation properties on a class of special Lototsky–Bernstein bases. We focus on approximation of | x | $|x|$ on [ − 1 , 1 ] $[-1,1]$ by an approximation process generated from fixed points on Lototsky–Bernstein bases. Our first result shows that the approximation procedure p n ( x ) $p_{n}(x)$ to | x | $|x|$ preserves good shapes on [ − 1 , 1 ] $[-1,1]$ . Moreover, some convergence results and inequalities are derived. Our second main result states that the rate convergence of the approximation is O ( n − 2 ) $O(n^{-2})$ .

This study aimed to evaluate the distribution of plasma troponin I concentration and establish the 99th percentile reference for hs-cTnI in a hospitalized population without a cardiovascular discharge diagnosis from the Shandong area.

Rock-encased-backfill (RB) structures are common in underground mining, for example in the cut-and-fill and stoping methods. To understand the effects of cyclic excavation and blasting activities on the damage of these RB structures, a series of triaxial stepwise-increasing-amplitude cyclic loading experiments was conducted with cylindrical RB specimens (rock on outside, backfill on inside) with different volume fractions of rock (VF = 0.48, 0.61, 0.73, and 0.84), confining pressures (0, 6, 9, and 12 MPa), and cyclic loading rates (200, 300, 400, and 500 N/s). The damage evolution and meso-crack formation during the cyclic tests were analyzed with results from stress-strain hysteresis loops, acoustic emission events, and post-failure X-ray 3D fracture morphology. The results showed significant differences between cyclic and monotonic loadings of RB specimens, particularly with regard to the generation of shear microcracks, the development of stress memory and strain hardening, and the contact forces and associated friction that develops along the rock-backfill interface. One important finding is that as a function of the number of cycles, the elastic strain increases linearly and the dissipated energy increases exponentially. Also, compared with monotonic loading, the cyclic strain hardening characteristics are more sensitive to rising confining pressures during the initial compaction stage. Another finding is that compared with monotonic loading, more shear microcracks are generated during every reloading stage, but these microcracks tend to be dispersed and lessen the likelihood of large shear fracture formation. The transition from elastic to plastic behavior varies depending on the parameters of each test (confinement, volume fraction, and cyclic rate), and an interesting finding was that the transformation to plastic behavior is significantly lower under the conditions of 0.73 rock volume fraction, 400 N/s cyclic loading rate, and 9 MPa confinement. All the findings have important practical implications on the ability of backfill to support underground excavations.

Knee osteoarthritis (OA) is a prevalent musculoskeletal condition affecting millions worldwide, posing significant health and economic burdens. Characterized by the degeneration of joint cartilage, the progression of knee OA varies significantly among individuals, making its prediction a complex issue. Previous studies on automated knee OA diagnosis have primarily relied on unimodal data, often overlooking the valuable information present in multi-modal data. Multi-modal learning, which integrates information from various modalities, is increasingly recognized for its potential to enhance diagnostic performance in medical applications. However, such models incur a higher computational load due to the additional data required. This research investigates the feasibility of multi-modal neural networks in knee OA diagnosis by integrating structural demographic data with unstructured imaging data. Three deep learning unimodal models (InceptionV3, DIKO, and EfficientNetv2) were transformed into multi-modal architectures (MF_InceptionNet, MF_DIKO, and MF_Eff) to compare their diagnostic capabilities. The proposed multi-modal models share a common architecture, with unimodal models acting as image feature extraction backbones and separate embedding layers for demographic data. The image features and demographic embeddings are combined into a unified vector before classification. Extensive experiments were conducted to evaluate the performance of these models across different class categories and dataset sizes. MF_DIKO and InceptionV3 emerged as the best multi-modal and unimodal neural networks, respectively, with overall accuracies of 0.67 and 0.75 for 3-class severity classification. Contrary to existing literature, our findings reveal that unimodal neural networks using only imaging features outperform multi-modal networks, suggesting unimodal models might suffice in certain applications.

3D lane detection from the input monocular image is a basic but indispensable task in the environment perception of automatic driving. Recent work uses modules such as depth estimation, coordinate system transformation, and time series tracking to achieve the correspondence of 2D to 3D information. However, inaccurate depth information generated by perturbations during conversion poses a challenge to lane detection methods that rely only on monocular images. To solve the above problems, we propose a PELD model, a proxy transformation using BEV aerial view, to explicitly give 3D lane detection results. Specifically, when sampling feature information, feature flipping is proposed to supplement the global context information before view conversion, and the 3D position encoding information generated by the forward-looking features enhances the depth information. After the 3D position encoding information is combined with the feature information, the cross-attention module is used as a value for adaptive supervision of BEV queries. On the one hand, we use deformable attention to sample forward looking features and generate explicit lane representation; on the other hand, we supplement supervised lane line generation by supplementing forward looking features and enhancing 3D spatial information. PELD implements a more advanced approach than ever before on OpenLane and Apollo datasets.

Crowdsourcing platforms provide an efficient and cost-effective means to acquire the extensive labeled data necessary for supervised learning. However, the labels provided by untrained crowdsourcing workers often contain a considerable amount of noise. Although the application of ground truth inference algorithms to deduce integrated labels effectively enhances label quality, a certain level of noise persists. To further diminish the noise within crowdsourced labeling, this paper introduces a novel Small Loss-based Noise Correction algorithm (SLNC). SLNC first filters the crowdsourced data, leveraging the characteristic of neural networks to preferentially fits clean samples, thereby obtaining relatively clean and noisy sets. It then employs data augmentation techniques to enhance the clean set and subsequently trains the corrector on this augmented set to rectify the noisy set. SLNC has been evaluated using 16 simulated and two real-world datasets. The results indicate that SLNC surpasses comparative algorithms in the quality of the final labels.

Abstract Introduction ‘Let’s Talk About Children’ is a brief family focused intervention developed to improve mental health outcomes of children of parents with mental illness (COPMI). This study aims to assess the efficacy of LTC in improving mental health of children of parents with schizophrenia or bipolar disorder in China. Methods The planned study is a multicentre parallel group randomized wait-list controlled trial. A total of 400 eligible families with children aged 8 to 18 years will be recruited, 200 each for families with parental schizophrenia or bipolar disorder. The intervention group will receive Let’s Talk About Children delivered by a trained therapist, while the control group will receive treatment as usual. The primary outcomes are child mental health measured by the strengths and difficulties questionnaire and parent–child communication measured using the parent-adolescent communication scale. Parental mental health and family functioning are secondary outcomes. This study also plans to explore mediating factors for the effect of Let’s Talk About Children on child mental health, as well as conduct a cost-effectiveness analysis on using Let’s Talk About Children in China. Conclusion The present study will provide evidence for the efficacy of Let’s Talk About Children in families with parental schizophrenia and bipolar disorder in China. In addition, it will evaluate potential mechanisms of action and cost-effectiveness of Let’s Talk About Children, providing a basis for future implementation. Trial registration ChiCTR2300073904.

This paper presents a systematic investigation and demonstration of a K-band circularly polarized liquid-crystal-based phased array (LCPA), including the design, over-the-air (OTA) in-array calibration, and experimental validation. The LCPA contains 16 phase-shifting radiating channels, each consisting of a circularly polarized stacked patch antenna and a liquid-crystal-based phase shifter (LCPS) based on a loaded differential line structure. Thanks to its slow-wave properties, the LCPS exhibits a maximum phase-shifting range of more than 360° with a figure of merit of 78.3(° )·dB−1 based on a liquid crystal layer with a thickness of only 5 μm. Furthermore, an automatic OTA calibration based on a state ergodic method is proposed, which enables the extraction of the phase–voltage curve of every individual LCPA channel. The proposed LCPA is manufactured and characterized with a total profile of only 1.76 mm, experimentally demonstrating a scanned circularly polarized beam from −40° to +40° with a measured peak gain of 12.5 dBic and a scanning loss of less than 2.5 dB. The bandwidth of the LCPA, which satisfies the requirements of port reflection (|S11|) < −15 dB, an axial ratio (AR) < 3 dB, beam squinting < 3°, and a gain variation < 2.2 dB, spans from 25.5 to 26.0 GHz. The total efficiency is about 34%, which represents a new state of the art. The use of the demonstrated low-profile LCPA to support circularly polarized scanning beams, along with the systematic design and calibration methodology, holds potential promise for a variety of millimeter-wave applications.

Abstract Background sCD25 is an important immune molecule for T cell regulation. Tracking the detection of plasma sCD25 plays an important role in the evaluation of immune function, progression, and prognosis of tuberculosis (TB) patients. This study analyzed the association of plasma sCD25 levels with clinical, laboratory, CT imaging characteristics, and clinical outcome of TB patients. Methods The clinical data of 303 TB patients treated in the Fifth People’s Hospital of Suzhou from October 2019 to January 2022 were retrospectively analyzed. The levels of sCD25 in plasma were detected by ELISA. According to the cut-off threshold of plasma sCD25 levels, the patients were divided into a low-value group (Group TB1) and a high-value group (Group TB2). The association of plasma sCD25 levels with clinical, laboratory, and CT imaging characteristics of TB patients, as well as their TB treatment outcome were analyzed. Results The levels of plasma sCD25 of patients with TB patients were higher than that of the healthy control group (P

Abstract Lung cancer is a leading cause of cancer deaths and imposes an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after an initial lung cancer diagnosis. The Cox proportional hazards model is mainly employed in survival analysis. However, real-world medical data are usually incomplete, posing a great challenge to the application of this model. Commonly used imputation methods cannot achieve sufficient accuracy when data are missing, so we investigated novel methods for the development of clinical prediction models. In this article, we present a novel model for survival prediction in missing scenarios. We collected data from 5,240 patients diagnosed with lung cancer at the Weihai Municipal Hospital, China. Then, we applied a joint model that combined a BN and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved good predictive performance in discrimination and calibration. We showed that combining the BN with the Cox proportional hazards model is highly beneficial and provides a more efficient tool for risk prediction.

Abstract Adipocytes play a significant role in breast cancer due to the unique histological structure of the breast. These have not only been detected adjacent to breast cancer cells but they have also been implicated in cancer development. Adipocytes in obese individuals and tumor microenvironment (TME) have a common feature, that is, hypoxia. The increased expression of hypoxia-inducible factor (HIF)-1α is known to alter the metabolism and functions of adipocytes. In this study, we described the mechanism linking the hypoxia-sensing pathway manifested by HIF to adipocytes and breast cancer and discussed the mechanism underlying the role of hypoxic adipocytes in breast cancer development from the perspective of metabolic remodeling. The processes and pathways in hypoxic adipocytes could be a promising target in breast cancer therapy.

Abstract There is significant heterogeneity in individual responses to antipsychotic drugs, but there is no reliable predictor of antipsychotics response in first-episode psychosis. This study aimed to investigate whether psychotic symptom-related alterations in fractional anisotropy (FA) and mean diffusivity (MD) of white matter (WM) at the early stage of the disorder may aid in the individualized prediction of drug response. Sixty-eight first-episode patients underwent baseline structural MRI scans and were subsequently randomized to receive a single atypical antipsychotic throughout the first 12 weeks. Clinical symptoms were evaluated using the eight “core symptoms” selected from the Positive and Negative Syndrome Scale (PANSS-8). Follow-up assessments were conducted at the 4th, 8th, and 12th weeks by trained psychiatrists. LASSO regression model and cross-validation were conducted to examine the performance of baseline symptom-related alterations FA and MD of WM in the prediction of individualized treatment outcome. Fifty patients completed both clinical follow-up assessments by the 8th and 12th weeks. 30 patients were classified as responders, and 20 patients were classified as nonresponders. At baseline, the altered diffusion properties of fiber tracts in the anterior thalamic radiation, corticospinal tract, callosum forceps minor, longitudinal fasciculi (ILF), inferior frontal-occipital fasciculi (IFOF) and superior longitudinal fasciculus (SLF) were related to the severity of symptoms. These abnormal fiber tracts, especially the ILF, IFOF, and SLF, significantly predicted the response to antipsychotic treatment at the individual level (AUC = 0.828, P

Abstract Background To analyze the association of serum Asprosin concentrations with heart failure (HF). Methods A total of 103 patients with HF were included in the HF group, and 103 patients with health checkups were included in the non-HF group. The serum Asprosin levels of the two groups were measured, and relevant clinical data were collected for statistical analysis. Results Compared with the non-HF group, the serum Asprosin concentration was significantly higher in the HF group, and the difference was statistically significant (P

Abstract Bladder cancer, a prevalent and heterogeneous malignancy, necessitates the discovery of pertinent biomarkers to enable personalized treatment. The mammalian target of rapamycin complex 1 (mTORC1), a pivotal regulator of cellular growth, metabolism, and immune response, exhibits activation in a subset of bladder cancer tumors. In this study, we explore the prognostic significance of mTORC1 signaling in bladder cancer through the utilization of bioinformatics analysis. Our investigation incorporates transcriptomic, somatic mutation, and clinical data, examining the mTORC1 score of each sample, as well as the enrichment of differentially expressed genes (DEGs), differentiation characteristics, immunological infiltration, and metabolic activity. Our findings reveal that elevated mTORC1 levels serve as an adverse prognostic indicator for bladder cancer patients, exhibiting a significant association with Basal-type bladder cancer. Patients with heightened mTORC1 activation display heightened levels of pro-carcinogenic metabolism. Additionally, these individuals demonstrate enhanced response to immunotherapy. Finally, we develop an mTORC1-related signature capable of predicting the prognosis of bladder cancer patients.The signature offers novel mTORC1-related biomarkers and provides fresh insights into the involvement of mTORC1 in the pathogenesis of bladder cancer.

Abstract Background Patients’ attitudes toward medication have been shown to be a predictor of nonadherence to antipsychotic treatment. However, most previous studies that explored this relationship used a cross-sectional design. It is important to explore the association of attitudes toward drugs with discontinuation at different time points during antipsychotic treatment. In this study, we investigated the association of attitudes toward drugs (measured by the Drug Attitude Inventory (DAI-10)) with adherence at seven time points (baseline, 4 weeks, 8 weeks, 12 weeks, 26 weeks, 39 weeks, and 52 weeks) during 1 year of treatment. Factors that were potentially associated with attitudes toward drugs at the time point of interest were also studied. Methods Demographic characteristics, psychopathology, social functioning, and attitudes toward drugs (measured by the DAI-10) were collected at baseline, 4 weeks, 8 weeks, 12 weeks, 26 weeks, 39 weeks and 52 weeks. The association of attitudes toward drugs (measured by DAI-10) with adherence at the seven time points was calculated using the Mann‒Whitney U test. The optimal cutoff point for the DAI-10 was then determined using receiver operating characteristic (ROC) analysis. Cox regression analysis was conducted to further investigate the association of DAI-10 scores with discontinuation, controlling for potential confounding variables. We used multiple regression analysis to identify the factors associated with DAI-10 scores. Results Among the six time points, only baseline DAI-10 total scores were significantly different between the completed and discontinued groups (p = 0.004). Female sex and a baseline DAI-10 total score greater than − 1 were found to be independent protective factors against discontinuation of antipsychotic drug treatments during the 1-year follow-up. At baseline, the severity of the disease (CGI-s) and insight regarding the disease were shown to be associated with DAI-10 total scores. Conclusion Attitudes toward antipsychotic drugs at baseline were shown to play a crucial role in predicting treatment discontinuation. Trial registration The data were collected from a clinical trial and the clinical trials.gov ID of the study is NCT01057849.

The blood–brain barrier (BBB) impairment plays a crucial role in the pathological processes of aging-accompanied neurological diseases (AAND). Meanwhile, circadian rhythms disruption and gut microbiota dysbiosis are associated with increased morbidity of neurological diseases in the accelerated aging population. Importantly, circadian rhythms disruption and gut microbiota dysbiosis are also known to induce the generation of toxic metabolites and pro-inflammatory cytokines, resulting in disruption of BBB integrity. Collectively, this provides a new perspective for exploring the relationship among circadian rhythms, gut microbes, and the BBB in aging-accompanied neurological diseases. In this review, we focus on recent advances in the interplay between circadian rhythm disturbances and gut microbiota dysbiosis, and their potential roles in the BBB disruption that occurs in AAND. Based on existing literature, we discuss and propose potential mechanisms underlying BBB damage induced by dysregulated circadian rhythms and gut microbiota, which would serve as the basis for developing potential interventions to protect the BBB in the aging population through targeting the BBB by exploiting its links with gut microbiota and circadian rhythms for treating AAND.

A cost-effective and sustainable noble-metal free catalyst system based on ubiquitously available Mn–Cu bimetallic oxides was served as efficient catalysts for furfural selective oxidation to furancarboxylic acid (FA). Interestingly, Mn2Cu1Ox exhibited an excellent furfural conversion of 99% with quantitative selectivity toward FA. Especially, we demonstrate the significant weakening of the Mn–O bonds with the incorporation of CuO into the Mn–Cu oxides, resulting in an improved OL reactivity of Mn2Cu1Ox, which brings about a higher catalytic activity for furfural oxidation. More importantly, Mn2Cu1Ox could exhibit YFA>90% over 5 cycles of reusability test. Through this study, the relationship between the morphology, surface chemistry, and catalytic activity of Mn–Cu bimetallic oxides are elucidated, providing a simple and environmentally friendly catalytic strategy and scientific basis for the development of Mn–Cu bimetallic oxides bioderived molecular aerobic oxidation materials.

This paper aims to shed new light on the religious function and symbolic meaning of parasols (san 傘) in Buddhist ritual practices, tracing the origins of the concept and examining its representations in texts and art. The author focuses on manuscripts, particularly the “Liturgies for Installing Parasols” (Ansan wen 安傘文) from Dunhuang, and argues that parasols were used as special ritual instruments to guard the local community. Their sacred power stemmed from the apotheosis of the parasol’s practical function of shielding and protecting people, which was further enhanced by beliefs surrounding the “Mother of Buddhas with Great White Canopy” (Da bai sangai fomu 大白傘蓋佛母) in the late Tang and Five Dynasties. Erecting parasols or carrying them in processions around the city was considered equivalent to demarcating boundaries, establishing defenses, and creating sanctuaries. Whether worn as a protective object, placed at the city’s four gates as a symbol of safeguarding passage, or installed in processions, the Great White Canopy Dhāraṇī and the practice of installing parasols distinguished the inside from the outside, self from others, and purity from impurity. This practice not only had the power to expel plagues and disasters, but also solemnified spaces, bringing blessings, purification, health, and peace. The parasol’s practical functions were continuously extended and mythologized, becoming a central object in rituals aimed at sanctifying space. The rise of the Great White Canopy Dhāraṇī belief in Dunhuang further reinforced its role in local customs. This method of spatial sanctification reflects the internal logic of esoteric Buddhist practices while sharing conceptual and technical similarities with traditional Chinese apotropaic arts (fangshu 方術) and Daoist exorcistic rituals. Through the grand and regular performance of these ceremonies, political legitimacy and communal well-being were successfully established.

Currently, NiFe-LDH exhibits an excellent oxygen evolution reaction (OER) due to the interaction of the two metal elements on the layered double hydroxide (LDH) platform. However, such interaction is still insufficient to compensate for its poor electrical conductivity, limited number of active sites and sluggish dynamics. Herein, a feasible two-step hydrothermal strategy that involves coupling low-conductivity NiFe-LDH with 3D porous graphene aerogel (GA) is proposed. The optimized NiFe-LDH/GA (1:1) produced possesses a 257 mV (10 mA cm−2) overpotential and could operate stably for 56 h in an OER. Our investigation demonstrates that the NiFe-LDH/GA has a three-dimensional mesoporous structure, and that there is synergistic interaction between LDH and GA and interfacial reconstruction of NiOOH. Such an interface synergistic coupling effect promotes fast mass transfer and facilitates OER kinetics, and this work offers new insights into designing efficient and stable GA-based electrocatalysts.

Objective: Advancements in neuroimaging technologies have significantly deepened our understanding of the neural physiopathology associated with stroke. Nevertheless, the majority of studies ignored the characteristics of dynamic changes in brain networks. The relationship between dynamic changes in brain networks and the severity of motor dysfunction after stroke needs further investigation. From the perspective of multilayer network module reconstruction, we aimed to explore the dynamic reorganization of the brain and its relationship with motor function in subcortical stroke patients. Methods: We recruited 35 healthy individuals and 50 stroke patients with unilateral limb motor dysfunction (further divided into mild-moderate group and severe group). Using dynamic multilayer network modularity analysis, we investigated changes in the dynamic modular reconfiguration of brain networks. Additionally, we assessed longitudinal clinical scale changes in stroke patients. Correlation and regression analyses were employed to explore the relationship between characteristic dynamic indicators and impairment and recovery of motor function, respectively. Results: We observed increased temporal flexibility in the Default Mode Network (DMN) and decreased recruitment of module reconfiguration in the Attention Network (AN), Sensorimotor Network (SMN), and DMN after stroke. We also observed reduced module loyalty following stroke. Additionally, correlation analysis showed that hyper-flexibility of the DMN was associated with better lower limb motor function performance in stroke patients with mild-to-moderate impairment. Regression analysis indicated that increased flexibility within the DMN and decreased recruitment coefficient within the AN may predict good lower limb function prognosis in patients with mild to moderate motor impairment. Conclusions: Our study revealed more frequent modular reconfiguration and hyperactive interaction of brain networks after stroke. Notably, dynamic modular remodeling was closely related to the impairment and recovery of motor function. Understanding the temporal module reconfiguration patterns in multilayer networks after stroke can provide valuable information for more targeted treatments.

Diffusion models have attracted considerable scholarly interest for their outstanding performance in generative tasks. However, current style transfer techniques based on diffusion models still rely on fine-tuning during the inference phase to optimize the generated results. This approach is not merely laborious and resource-demanding but also fails to fully harness the creative potential of expansive diffusion models. To overcome this limitation, this paper introduces an innovative solution that utilizes a pretrained diffusion model, thereby obviating the necessity for additional training steps. The scheme proposes a Feature Normalization Mapping Module with Cross-Attention Mechanism (INN-FMM) based on the dual-path diffusion model. This module employs soft attention to extract style features and integrate them with content features. Additionally, a parameter-free Similarity Attention Mechanism (SimAM) is employed within the image feature space to facilitate the transfer of style image textures and colors, while simultaneously minimizing the loss of structural content information. The fusion of these dual attention mechanisms enables us to achieve style transfer in texture and color without sacrificing content integrity. The experimental results indicate that our approach exceeds existing methods in several evaluation metrics.

Supplementation with benzoic acid (BA) in animal feed can reduce feeds’ acid-binding capacity, inhibit pathogenic bacterial growth, enhance nutrient digestion, and increase intestinal enzyme activities. This study aimed to investigate the effects of different doses of BA on the growth performance, rumen fermentation, and rumen microbiota of weaned Holstein dairy calves. Thirty-two Holstein calves at 60 days of age were randomly assigned into four groups (n = 8): a control group (fed with a basal diet without BA supplementation; CON group) and groups that were supplemented with 0.25% (LBA group), 0.50% (MBA group), and 0.75% (HBA group) BA to the basal diet (dry matter basis), respectively. The experiment lasted for 42 days, starting at 60 days of age and ending at 102 days of age, with weaning occurring at 67 days of age. Supplementation with BA linearly increased the average daily gain of the weaned dairy calves, which was significantly higher in the LBA, MBA, and HBA groups than that in the CON group. The average daily feed intake was quadratically increased with increasing BA supplementation, peaking in the MBA group. Supplementation with BA linearly decreased the feed-to-gain (F/G) ratio, but did not affect rumen fermentation parameters, except for the molar proportion of butyrate and iso-butyrate, which were linearly increased with the dose of BA supplementation. Compared with the CON group, the molar proportions of iso-butyrate in the LBA, MBA, and HBA groups and that of butyrate in the HBA group were significantly higher than those in the CON group. Supplementation with BA had no significant effect on the alpha and beta diversity of the rumen microbiota, but significantly increased the relative abundances of beneficial bacteria, such as Bifidobacterium, and reduced those of the harmful bacteria, such as unclassified_o__Gastranaerophilales and Oscillospiraceae_UCG-002, in the rumen. Functional prediction analysis using the MetaCyc database revealed significant variations in the pathways associated with glycolysis across groups, including the GLYCOLYSIS-TCA-GLYOX-BYPASS, GLYCOL-GLYOXDEG-PWY, and P105-PWY pathways. In conclusion, BA supplementation improved the composition and function of rumen microbiota, elevated the production of butyrate and iso-butyrate, and increased the growth performance of weaned Holstein dairy calves.

As age increases, children will face more and more adversity. How effectively they cope with stress and difficulties of life is of great significance to the development of children’s mental health and academic achievement. However, few studies have explored how different interpersonal relationships and psychological suzhi work together to influence children’s healthy behaviors, particularly healthy coping in adversity. Therefore, this research focused on the teacher–student relationships and coping styles, as well as the chain-mediated effects of peer relationships and psychological suzhi. A total of 688 children (360 boys, 52.3%; Mage = 10.98 and SD = 0.89) completed questionnaires that assessed using teacher–student relationships, peer relationships, psychological suzhi, and coping styles. The results indicated that teacher–student relationships correlated positively with coping styles, peer relationships, and psychological suzhi in children. Besides, teacher–student relationships positively affected coping styles through both the mediating roles of peer relationships and psychological suzhi. This research elucidated the extrinsic and intrinsic factors impacting the coping styles of children, thus providing empirical validation of existing theoretical frameworks. In China, interventions aimed at promoting Chinese children’s positive coping could benefit from strategies focused on cultivating high-quality relationships and enhancing psychological suzhi.

Abstract Electrochromic (EC) technology has been regarded as a promising energy‐saving technology in various applications, including smart windows, displays, thermal management, rear views, etc. Benefiting from the progress in electrochromic material synthesis, electrochromic electrode fabrication, and electrochromic device configuration design, the focus in electrochromic community has gradually shifted to multifunctional electrochromic devices (ECDs) in the era of Internet of Things. Multifunctional ECDs, such as electrochromic energy storage devices, multi‐color displays, deformable ECDs, smart windows, etc. have been showcased the ability to expand potential applications. In this review, the available device configurations, performance indexes and advanced characterization techniques for multifunctional ECDs are introduced and classified accordingly. The applications of multifunctional ECDs for energy storage, multicolor displays, deformable devices, self‐chargeable devices, smart windows, actuators, etc., are exemplified. The future development trends and perspectives of multifunctional ECDs are also overlooked. The aim of this review is to guide and inspire further efforts in the exploration of novel and advanced multifunctional ECDs.

IntroductionInflammatory bowel disease (IBD) is a chronic disease involving multiple genes, and the current available targeted drugs for IBD only deliver moderate efficacy. Whether there is a single gene that systematically regulates IBD is not yet known. MiR-146a plays a pivotal role in repression of innate immunity, but its function in the intestinal inflammation is sort of controversy, and the genetic regulatory networks regulated by miR-146a in IBD has not been revealed.MethodsRT-qPCR was employed to detect the expression of miR-146a in IBD patients and in a mouse IBD model induced by dextran sulfate sodium (DSS), and then we generated a miR-146a knock-out mouse line with C57/Bl6N background. The disease activity index was scored in DSS-treated miR-146a deficiency mice and their wild type (WT) littermates. Bulk RNA-sequencing, RT-qPCR and immunostaining were done to illustrate the downstream genetic regulatory networks of miR-146a in flamed colon. Finally, the modified miR-146a mimics were used to treat DSS-induced IBD in miR-146a knock-out and WT IBD mice.ResultsWe showed that the expression of miR-146a in the colon was elevated in dextran sulfate sodium (DSS)-induced IBD mice and patients with IBD. DSS induced dramatic body weight loss and more significant rectal bleeding, shorter colon length, and colitis in miR-146a knock-out mice than WT mice. The miR-146a mimics alleviated DSS-induced symptoms in both miR-146a-/- and WT mice. Further RNA sequencing illustrated that the deficiency of miR-146a de-repressed majority of DSS-induced IBD-related genes that cover multiple genetic regulatory networks in IBD, and supplementation with miR-146a mimics inhibited the expression of many IBD-related genes. Quantitative RT-PCR or immunostaining confirmed that Ccl3, Saa3, Csf3, Lcn2, Serpine1, Serpine2, MMP3, MMP8, MMP10, IL1A, IL1B, IL6, CXCL2, CXCL3, S100A8, S100A9, TRAF6, P65, p-P65, and IRAK1 were regulated by miR-146a in DSS induced IBD. Among them, MMP3, MMP10, IL6, IL1B, S100A8, S100A9, SERPINE1, CSF3, and IL1A were involved in the active stage of IBD in humans.DiscussionOur date demonstrated that miR-146a acts as a top regulator in C57/BL6N mice to systematically repress multiple genetic regulatory networks involved in immune response of intestine to environment factors, and combinatory treatment with miR-146a-5p and miR-146a-3p mimics attenuates DSS-induced IBD in mice through down-regulating multiple genetic regulatory networks which were increased in colon tissue from IBD patients. Our findings suggests that miR-146a is a top inhibitor of IBD, and that miR-146a-5p and miR-146a-3p mimics might be potential drug for IBD.

Background: Based on the bioinformatics prediction, this study investigates the correlation between aberrant transcription factor Frizzled 5 (FZD5) expression and the establishment of non-small cell lung cancer (NSCLC). Methods: A mouse model with regard to primary NSCLC was encouraged by intraperitoneal injection of urethane. Lentivirus-based FZD5 silencing was then administrated to examine its role in tumorigenesis in the mouse lung. Silencing of FZD5 was induced in two NSCLC cell lines to examine its function in the malignant behavior pertaining to cells in vitro. Quantitative methylation-specific PCR was employed to assess the DNA methylation level within the NSCLC cells. DNA methyltransferases (DNMTs) that administer FZD5 were assessed by chromatin immunoprecipitation assay. Consequently, overexpression of DNMT3A was introduced in mice and NSCLC cells to verify its regulation on FZD and its biological roles in NSCLC development. Results: In NSCLC, FZD5 expression is elevated, and its knockdown reduced tumor incidence rate in the urethane-challenged mice. The FZD5 silencing also inhibited proliferation, migration, as well as invasion with regard to Calu-3 and NCI–H1299 cells in vitro. The aberrant upregulation with regard to FZD5 in NSCLC was due to at least partly by reduced promoter methylation level. DNMT3A, which bound to FZD5 promoter to suppress its transcription, was poorly expressed in NSCLC. Artificial upregulation of DNMT3A suppressed urethane-induced lung carcinogenesis in mice and suppressed the malignant phenotype pertaining to NSCLC cells in vitro. Conclusion: This research demonstrates that the lack of DNA methylation level-induced activation of FZD5 is correlated with NSCLC's onset and progression.

Metallic coatings are widely employed to improve the oxidation resistance of superalloys. However, the interdiffusion between the metallic coatings and the superalloys leads to microstructural degradation in both. Some of the underlying degradation mechanisms are still elusive, e.g., the γ′ (Ni3Al) phase depletion in superalloys, where a large amount of γ′ precipitates are dissolved in the γ matrix even though the incoming Al from coatings indeed increases the Al content. Here, we investigated the interdiffusion behavior between the Amdry365 coating and the IN792 superalloy at 1100 °C, using multiple microscopic techniques and thermodynamics calculations. Our results showed an excellent agreement between experiments and thermodynamics simulations, indicating the dominant role of Al on the initial diffusion-induced phase transitions. We proposed the Al-Cr interference effect to account for the pile-up behavior of Cr and the reduced Al content near the coating/superalloy interface. The local phase equilibrium calculations revealed that the γ′ depletion in the superalloy is primarily attributed to the loss of γ′-forming elements, such as Ta and Ti. Our findings opened up an avenue for studies on the superalloy/coating interdiffusion, contributing to reducing this damaging impact.

Benzene is a known contributor to human leukaemia through its toxic effects on bone marrow cells, and epigenetic modification is believed to be a potential mechanism underlying benzene pathogenesis. However, the specific roles of N6-methyladenosine (m6A), a newly discovered RNA post-transcriptional modification, in benzene-induced hematotoxicity remain unclear. In this study, we identified self-renewing malignant proliferating cells in the bone marrow of benzene-exposed mice through in vivo bone marrow transplantation experiments and Competitive Repopulation Assay. Subsequent analysis using whole transcriptome sequencing and RNA m6A methylation sequencing revealed a significant upregulation of RNA m6A modification levels in the benzene-exposed group. Moreover, RNA methyltransferase METTL14, known as a pivotal player in m6A modification, was found to be aberrantly overexpressed in Lin-Sca-1+c-Kit+ (LSK) cells of benzene-exposed mice. Further analysis based on the GEO database showed a positive correlation between the expression of METTL14, mTOR, and GFI and benzene exposure dose. In vitro cellular experiments, employing experiments such as western blot, q-PCR, m6A RIP, and CLIP, validated the regulatory role of METTL14 on mTOR and GFI1. Mechanistically, continuous damage inflicted by benzene exposure on bone marrow cells led to the overexpression of METTL14 in LSK cells, which, in turn, increased m6A modification on the target genes’ (mTOR and GFI1) RNA. This upregulation of target gene expression activated signalling pathways such as mTOR-AKT, ultimately resulting in malignant proliferation of bone marrow cells. In conclusion, this study offers insights into potential early targets for benzene-induced haematologic malignant diseases and provides novel perspectives for more targeted preventive and therapeutic strategies.

Accurate calculations and precise results are very important for the dissemination of scientific knowledge, whereas the errors of calculation will diminish the academic value of the paper. This discussion focuses on the calculation of thermodynamics and the determination of the spontaneity of adsorption processes in the paper of Ofudje et al. (2023). Ofudje et al. found that the apatite synthesized by chemical method (CHAp) has excellent adsorption properties for cadmium ions, which is an important contribution to the remediation of cadmium pollution. However, the calculation results of standard Gibbs free energy change (ΔGo), standard enthalpy change (ΔHo) and standard entropy change (ΔSo) of the adsorption of Cd2+ onto CHAp surface need to be corrected due to an incorrect calculation. Firstly, the partition coefficient (KD) with a dimension cannot be used for thermodynamic calculation. Secondly, the adsorbent mass (m) described by Ofudje et al. in different Sections is inconsistent, leading to incorrect results of Ko and ΔGo. When the appropriate value of the adsorbent mass is selected and the partition coefficient is converted to the standard adsorption equilibrium constant Ko, the calculated ΔGo is less than zero, which means that the adsorption is spontaneous. This discussion provides the correct calculation method of standard adsorption equilibrium constants and thermodynamic parameters, which can improve the reader's judgment and understanding of adsorption spontaneity.

BackgroundThe efficacy and safety of different immunosuppressants combined with chemotherapy in treating patients with small-cell lung cancer (extensive-disease small-cell lung cancer, limited-disease small-cell lung cancer and relapsed small-cell lung cancer) are still unknown, and there are no reports directly comparing the efficacy and safety of other immunotherapies.ObjectiveThis study aimed to compare the efficacy and safety of first-line immunotherapy combined with chemotherapy in patients with small-cell lung cancer.MethodWe searched Pubmed, Embase, Cochrane Library, CNKI, and Wanfang databases for relevant articles published from inception to November 11, 2020. The risk of bias of the included studies was conducted using the Cochrane risk-of-bias (RoB) tool. Multiple Bayesian network meta-analyses were performed. They conducted data analysis using R Studio and STATA version 15.1. The outcomes comprised overall survival (OS), progression-free survival (PFS), stability of response (SOR), duration of response (DOR) and adverse events of grade 3 or higher (AE grade≥3). A 95% confidence interval (CI) was provided for each estimate.ResultsThis meta-analysis included 16 RCT studies with 5898 patients. For OS, relative to chemotherapy (MD=-4.49; 95%CI [-7.97, -1.03]), durvalumab plus tremelimumab (MD=-4.62; 95%CI [-9.08, -0.11]), ipilimumab (MD=-4.26; 95%CI [-8.01, -0.3]) and nivolumab(MD=-5.66; 95%CI [-10.44, -1.11]) and nivolumab plus ipilimumab (MD=-4.56; 95%CI [-8.7, -0.1]), serplulimab can significantly increase the OS of SCLC patients. There was no significant difference between PFS, SOR and DOR. Analysis of AE showed that different immunotherapy combined chemotherapy regimens were similar to single chemotherapy regarding the overall incidence of AE grade≥3. However, after the cumulative ranking of the common symptoms of different adverse reactions, it was found that nivolumab ranked first in the occurrence probability of anemia (99.08%), fatigue (84.78%), and decreased appetite (89.66%). durvalumab was the most likely in nausea (75.4%). Pembrolizumab (76.24%) was most likely to cause pruritus. Chemotherapy combined with immunotherapy caused less diarrhea than chemotherapy alone (80.16%).ConclusionsAccording to our analysis, serplulimab combined with chemotherapy is more likely to show better efficacy with a manageable safety profile for small-cell lung cancer. However, the evidence for this comparison shows some limitations due to the number of literature.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023486053.

Background: Immunotherapy has become the standard treatment for advanced non-small cell lung cancer (NSCLC). However, a subset of the most advanced NSCLC patients fails to respond adequately to Immune checkpoint inhibitors (ICIs). Developing new nomograms and integrating prognostic factors are crucial for improving the clinical predictability of NSCLC patients undergoing ICIs. Methods: Clinical information and genomic data of NSCLC patients undergoing ICIs were retrieved from cBioPortal. Gene alterations associated with durable clinical benefit (DCB) were compared to those linked to no durable benefit (NDB). The Kaplan-Meier plot method was employed for survival analysis, and a novel nomogram was formulated by selecting pertinent clinical variables. Results: For the NSCLC patients receiving immunotherapy, three subgroups were identified based on the treatment regimen, including anti-PD-1 monotherapy, anti-PD-1 combination with anti–CTLA–4, and first-line treatment. The mutation status of TP53, PGR, PTPRT, RELN, MUC19, LRP1B, and FAT3 was found to be associated with progression-free survival (PFS). Using the clinicopathological parameters and genomic data of the patients, we developed three novel nomograms to predict the prognosis of ICI treatment in different subgroups. Conclusion: Our study revealed that PGR, PTPRD, RELN, MUC19, LRP1B, and FAT3 mutation could serve as predictive biomarkers. Our systematic nomograms demonstrate significant potential in predicting the prognosis for NSCLC patients with sensitivity to different ICI treatment strategies.

The biocurrent generated by soil extracellular electron transfer (EET) partly drives biogeochemical cycles and controls soil quality. However, it is unclear how the soil abiotic and biotic conditions affect the biocurrent conduction. In this study, the response relationship of soil microenvironment and in-situ biocurrent was studied. The results showed that red soil exhibited the optimal electron transfer efficiency, as evidenced by the maximum current density and accumulated charge output, with increments of 56–93 % and 80–2800 %, respectively, compared with the other five types of soils. Soil physicochemical properties were the most important factor on the biocurrent generation, and further the quantity and bioavailability of dissolved organic matter, NH4+-N content, and lower pH were predictive indicators for the exoelectrogenic processes of soils. In addition, the high soil biocurrent was likely determined by a complex synergistic network of the transformation of carbon and nitrogen, electroactive bacteria involving the functions of cell wall/membrane and cytochrome enzyme metabolism and transport related EET process. Overall, we provide an insight into the relationship among soil biocurrent conduction, physicochemical properties, bacteria community and metabolic function, and a support for bioelectrochemical technology application.