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As a commonly used traditional Chinese medicine formula for treating rheumatoid arthritis (RA), Sishen Decoction (SSD) has anti-inflammatory, analgesic and swelling relief effects. However, at present, the pharmacodynamic basis of SSD and its mechanism of treating RA have not been clarified, and further research is needed. Analyzing the pharmacological basis of SSD was the aim of our study and further elucidate its therapeutic mechanism and potential targets for treating RA. LC‒MS was used to identify the high content and characteristic chemical components of SSD. On this basis, a network of pharmacological analysis was established between the chemical structure and RA. According to the predicted possible pathways and targets, in vivo pharmacodynamic experiments and related pathway analysis were conducted. Finally, the possible targets and mechanisms of SSD in treating RA were analyzed. Identified 78 compounds from SSD by LC-MS, including 23 flavonoids, 19 phenolic acids, 9 monoterpenoids and 26 other compounds. Network pharmacological analysis based on pharmacodynamic substances revealed that the most likely interaction pathway between SSD and RA was the PI3K/AKT/mTOR pathway. Foot swelling and inflammatory factors (IL-6, IL-10, IL-18, TGF, TNF-α, VEGF) in model mice were shown to be significantly improved in vivo. WB and qPCR experiments proved that SSD could significantly regulate the pathway of PI3K/AKT/mTOR. The interaction between SSD and AKT target was further analyzed by multispectroscopy. This study revealed that SSD alleviates RA by regulating the pathway of PI3K/AKT/mTOR and preliminarily revealed the pharmacodynamic mechanism of SSD for the first time.

Immunotherapy using inflammatory cytokines, such as interleukin (IL)-2 and interferon (IFN)-α, has been clinically validated in treating various cancers. However, systemic immunocytokine-based therapies are limited by the short half-life of recombinant proteins and severe dose-limiting toxicities. In this study, we exploited local immunotherapy by intratumoral administration of lipid nanoparticle (LNP)-encapsulated mRNA cocktail encoding cytokines IL-12, IL-7, and IFN-α. The cytokine mRNA cocktail induced tumor regression in multiple syngeneic mouse models and anti-tumor immune memory in one syngeneic mouse model. Additionally, immune checkpoint blockade further enhanced the anti-tumor efficacy of the cytokine mRNAs. Furthermore, human cytokine mRNAs exhibited robust anti-tumor efficacy in humanized mouse tumor models. Mechanistically, cytokine mRNAs induced tumor microenvironment inflammation, characterized by robust T cell infiltration and significant inflammatory cytokine and chemokine production.

Summary: Background: Shotgun metagenomic next-generation sequencing (mNGS) is widely used to detect pathogens in bronchoalveolar lavage fluid (BALF). However, mNGS is complex and expensive. This study explored the feasibility of targeted next-generation sequencing (tNGS) in distinguishing lower respiratory tract infections in clinical practice. Methods: We used 229 retrospective BALF samples to establish thresholds and diagnostic values in a prospective cohort of 251 patients. After target pathogen selection, primer and probe design, optimization experiments, and bioinformatics analysis, multiplex PCR-based tNGS (mp-tNGS) and hybrid capture-based tNGS (hc-tNGS), targeting 198 and 3060 pathogens (DNA and RNA co-detection workflow) were established and performed. Findings: mp-tNGS and hc-tNGS took 10.3 and 16 h, respectively, with low sequencing data sizes of 0.1 M and 1 M reads, and test costs reduced to a quarter and half of mNGS. The LoDs of mp-tNGS and hc-tNGS were 50–450 CFU/mL. mp-tNGS and hc-tNGS were highly accurate, with 86.5% and 87.3% (vs. 85.5% for mNGS) sensitivities and 90.0% and 88.0% (vs. 92.1% for mNGS) specificities. tNGS detection rates for casual pathogens were 84.3% and 89.5% (vs. 88.5% for mNGS), significantly higher than conventional microbiological tests (P

Summary: Motor neurons are highly polarized, and their axons extend over great distances to form connections with myofibers via neuromuscular junctions (NMJs). Local translation at the NMJs in vivo has not been identified. Here, we utilized motor neuron-labeled RiboTag mice and the TRAP (translating ribosome affinity purification) technique to spatiotemporally profile the translatome at NMJs. We found that mRNAs associated with glucose catabolism, synaptic connection, and protein homeostasis are enriched at presynapses. Local translation at the synapse shifts from the assembly of cytoskeletal components during early developmental stages to energy production in adulthood. The mRNA of neuronal Agrin (Agrn), the key molecule for NMJ assembly, is present at motor axon terminals and locally translated. Disrupting the axonal location of Agrn mRNA causes impairment of synaptic transmission and motor functions in adult mice. Our findings indicate that spatiotemporal regulation of mRNA local translation at NMJs plays critical roles in synaptic transmission and motor functions in vivo.

Background: Understanding the relationship between depression severity, patient recovery, and treatment continuity may help optimize the delivery of behavioral health services. Methods: Using Cox proportional hazards regression, this study measures the association between treatment dropout and baseline depression severity, as measured by the Patient Health Questionnaire (PHQ-9), and the association between treatment dropout and baseline recovery, as measured by the Recovery Assessment Scale (RAS). The study also explores heterogeneity by service line (general mental health, substance use disorder, and eating disorder), residential versus intermediate level of care setting, age groups (adolescent and adult), and dropout factors. The data include 14,689 patients treated at a multi-state behavioral health care provider, discharged between 2021 and 2022. Premature dropout from behavioral health care treatment for any cause, patient factors and administrative factors were used as separate outcomes. Findings: A unit increase in baseline PHQ-9 was associated with a 1.2% reduced treatment dropout risk (hazard ratio (HR): 0.988; 95% confidence interval [0.983–0.992]). A unit increase in baseline RAS score was associated with 0.5% increased dropout likelihood (HR: 1.005; 95% CI [1.004, 1.007]). Subgroup analyses show associations are driven by general mental health, adolescent, and intermediate level of care subgroups. Patients with higher baseline suicidality and lower willigness to ask for helphad a reduced risk of dropout. Interpretation: Patients with greater depression severity and lower recovery scores at admission were more likely to stay in behavioral health treatment, especially among adolescents, patients with general mental health issues, and outpatients.

Osteosarcoma, one of the most common primary malignancies in children and adolescents, has the primary characteristics of a poor prognosis and high rate of metastasis. This study used super-enhancer-related genes derived from two different cell lines to construct five novel super-enhancer-related gene prognostic models for patients with osteosarcoma. The training and testing datasets were used to confirm the prognostic models of the five super-enhancer-related genes, which resulted in an impartial predictive element for osteosarcoma. The immunotherapy and prediction of the response to anticancer drugs have shown that the risk signature of the five super-enhancer-related genes positively correlate with chemosensitivity. Furthermore, functional analysis of the risk signature genes revealed a significant relationship between gene groups and the malignant characteristics of tumours. TNF Receptor Superfamily Member 11b (TNFRSF11B) was selected for functional verification. Silencing of TNFRSF11B suppressed the proliferation, migration, and invasion of osteosarcoma cells in vitro and suppressed osteosarcoma growth in vivo. Moreover, transcriptome sequencing was performed on MG-63 cells to study the regulatory mechanism of TNFRSF11B in osteosarcoma cells, and it was discovered that TNFRSF11B is involved in the development of osteosarcoma via the phosphoinositide 3-kinase signalling pathway. Following the identification of TNFRSF11B as a key gene, we selected an inhibitor that specifically targeted this gene and performed molecular docking simulations. In addition, risedronic acid inhibited osteosarcoma growth at both cellular and molecular levels. In conclusion, the super-enhancer-related gene signature is a viable therapeutic tool for osteosarcoma prognosis and treatment.

Abstract Malignant tumors are a common cytopathologic disease. Pathological tissue examination is a key tool for diagnosing malignant tumors. Doctors need to manually analyze the images of pathological tissue sections, which is not only time-consuming but also highly subjective, easily leading to misdiagnosis. Most of the existing computer-aided diagnostic techniques focus too much on accuracy when processing pathological tissue images, and do not take into account the problems of insufficient resources in developing countries to meet the training of large models and the difficulty of obtaining medical annotation data. Based on this, this study proposes an artificial intelligence multiprocessing scheme (MSPInet) for digital pathology images of malignant tumors. We use techniques such as data expansion and noise reduction to enhance the dataset. Then we design a coarse segmentation method for cell nuclei of pathology images based on Transformer for Semantic Segmentation and further optimize the segmentation of tumor edges using conditional random fields. Finally, we improve the training strategy for knowledge distillation. As a medical assistive system, the method can quantify and convert complex pathology images into analyzable image information. Experimental results show that our method performs well in terms of segmentation accuracy and also has advantages in terms of time and space efficiency. This makes our technology available to developing countries that are not as well resourced, and equipped in terms of medical care. The teacher model and lightweight student model included in our method achieve 71.6% and 66.1% Intersection over Union (IoU) in cell segmentation respectively, outperforming Swin-unet and CSWin Transformer.

Abstract To counterbalance the abilities of global exploration and local exploitation of algorithm and enhance its comprehensive performance, a multi-objective particle swarm optimization with a competitive hybrid learning strategy (CHLMOPSO) is put forward. With regards to this, the paper first puts forward a derivative treatment strategy of personal best to promote the optimization ability of particles. Next, an adaptive flight parameter adjustment strategy is designed in accordance with the evolutionary state of particles to equilibrate the exploitation and exploration abilities of the algorithm. Additionally, a competitive hybrid learning strategy is presented. According to the outcomes of the competition, various particles decide on various updating strategies. Finally, an optimal angle distance strategy is proposed to maintain archive effectively. CHLMOPSO is compared with other algorithms through simulation experiments on 22 benchmark problems. The results demonstrate that CHLMOPSO has satisfactory performance.

The difference schemes constructed on the basis of one-dimensional uniform grids must be extended to non-uniform or curvilinear grids in practical applications, and the coordinate transformation process introduces geometry-induced errors. The accuracy of the difference schemes is evaluated by the accuracy test, in which the convergence solution error varies with the grid refinement. In this paper, the first-order upwind scheme, the second-order MUSCL scheme and the fifth-order WENO scheme were used to calculate the uniform free flow problem with constant flow parameters on a two-dimensional cylindrical coordinate uniform grid system, and the slope of the convergence curve was compared according to the accuracy test method, and it was found that the grid convergence accuracy of the first-order upwind scheme was second order, and the grid convergence accuracy of the fifth-order WENO scheme was less than first order. Theoretical analysis shows that this accuracy test method is not equivalent to the definition of difference scheme accuracy, and the data used cannot reflect the inherent defects of the difference scheme. Therefore, it cannot be used as a criterion for evaluating the accuracy of the difference scheme. Many studies of WENO schemes often simulate benchmarks such as the double Mach reflection problem and the two-dimensional Riemann problem, and use whether the contact discontinuity develops into an unstable vortex structure as a characteristic of the algorithm with high accuracy, which can be theoretically proved to be a non-physical phenomenon, so it is not appropriate to use whether a vortex structure appears as an argument for the algorithm′s high accuracy.

AlCoCrFeNi2.1 eutectic high-entropy alloy (EHEA), with its distinctive heterogeneous structure, not only overcomes the drawback of insufficient strength of FCC single-phase high-entropy alloys (HEAs), but also overcomes the drawback of insufficient ductility of BCC single-phase HEAs, making it a promising candidate for engineering application. In addition, EHEAs possessing excellent castability are considered to be suitable for additive manufacturing (AM). The AlCoCrFeNi2.1 EHEA prepared by direct energy deposition (DED) exhibits a dual-phase structure consisting of FCC(L12) and BCC(B2) phases. With the increase of deposition height, its morphology transforms from columnar and dendrite structures to lamellar structure. Furthermore, the tensile strength and yield strength of the DED-ed EHEA samples increase, while the ductility decreases with the increase of deposition height. Especially, the middle region of the DED-ed samples achieves a good strength-ductility balance. The lamellar structure composed of soft FCC(L12) phase and hard BCC(B2) phase produces a hetero deformation induced (HDI) hardening, which improves the strength of the samples and promotes plastic deformation. The FCC(L12)/BCC(B2) phase interfaces not only hinder the movement of a large number of dislocations and cause dislocation pile-up, but also allow some dislocations to slip across, which helps to plastic co-deformation of two phases in the EHEA samples. This work provides useful guidance for the performance improvement of EHEAs using laser additive manufacturing.

Abstract Meniscus pathologies (damage, extrusion) and synovitis are associated with knee osteoarthritis (KOA); however, whether synovitis mediates the relationship between meniscus pathologies and KOA radiographic progression remains unclear. We conducted an observational study in the Osteoarthritis Initiative (OAI) cohort, with a 48-month follow-up. Meniscus pathology and synovitis were measured by MRI osteoarthritis knee score (MOAKS) at baseline and 24 months, and a comprehensive synovitis score was calculated using effusion and Hoffa synovitis scores. The knee osteoarthritis radiographic progression was considered that Kellgren–Lawrence (KL) grade and joint space narrowing (JSN) grade at 48 months were increased compared to those at baseline. This study included a total of 589 participants, with KL grades mainly being KL1 (26.5%), KL2 (34.1%), and KL3 (30.2%) at baseline, while JSN grades were mostly 0 at baseline. A logistic regression model was used to analyze the relationship between meniscus pathology, synovitis, and KOA progression. Mediation analysis was used to evaluate the mediation effect of synovitis. The average age of the participants was 61 years old, 62% of which were female. The medial meniscus extrusion was longitudinally correlated with the progression of KL (odds ratio [OR]: 2.271, 95% confidence interval [CI]: 1.412–3.694) and medial JSN (OR: 3.211, 95% CI: 2.040–5.054). Additionally, the longitudinal correlation between medial meniscus damage and progression of KOA (OR: 1.853, 95% CI: 1.177–2.941) and medial JSN (OR: 1.655, 95% CI: 1.053–2.602) was significant. Synovitis was found to mediate the relationship between medial meniscus extrusion and KL and medial JSN progression at baseline (β: 0.029, 95% CI: 0.010–0.053; β: 0.022, 95% CI: 0.005–0.046) and beyond 24 months (β: 0.039, 95% CI: 0.016–0.068; β: 0.047, 95% CI: 0.020–0.078). However, we did not find evidence of synovitis mediating the relationship between meniscal damage and KOA progression. Synovitis mediates the relationship between medial meniscus extrusion (rather than meniscus damage) and KOA progression.

Abstract Background The feasibility and safety of laparoscopic pancreatoduodenectomy (LPD) in elderly patients is still controversial. This study aimed to compare the clinical outcomes of LPD and open pancreatoduodenectomy (OPD) in elderly patients. Methods Clinical and follow-up data of elderly patients (≥ 65 years) who underwent LPD or OPD between 2015 and 2022 were retrospectively analyzed. A 1:1 propensity score-matching (PSM) analysis was performed to minimize differences between groups. Univariate and multivariate logistic regression analysis were used to select independent prognostic factors for 90-day mortality. Results Of the 410 elderly patients, 236 underwent LPD and 174 OPD. After PSM, the LPD group had a less estimated blood loss (EBL) (100 vs. 200 mL, P 0.05). Multivariate logistic regression analysis showed that post-pancreatectomy hemorrhage (PPH) was an independent risk factor for 90-day mortality. Elderly patients with pancreatic ductal adenocarcinoma (PDAC) who underwent LPD or OPD had similar overall survival (OS) (22.5 vs.20.4 months, P = 0.672) after PSM. Conclusions It is safe and feasible for elderly patients to undergo LPD with less EBL and a shorter postoperative LOS. There was no statistically significant difference in long-term survival outcomes between elderly PDAC patients who underwent LPD or OPD.

Abstract Background Postural abnormalities (PA) are common in the advanced stages of Parkinson’s disease (PD), but effective therapies are lacking. A few studies suggested that spinal cord stimulation (SCS) could be a potential therapy whereas its effect is still uncertain. We aimed to investigate whether SCS had potential for benefiting PD patients with PA. Methods T8-12 SCS was operated on six PD patients with PA and all patients were followed for one year. Evaluations were made before and after SCS. Moreover, three patients were tested separately with SCS on-state and off-state to confirm the efficacy of SCS. Results Improvements in lateral trunk flexion degree, anterior thoracolumbar flexion degree and motor function were found after SCS. The improvements diminished while SCS was turned off. Conclusions Lower thoracic SCS may be effective for improving PA in PD patients, but further studies are needed to confirm this conclusion. Trial registration Chinese Clinical Trial Registry, ChiCTR1900024326, Registered on 6th July 2019; https://www.chictr.org.cn/showproj.aspx?proj=40835 .

Abstract In plants, the plant-specific RNA polymerase V (Pol V) transcripts non-coding RNAs and provides a docking platform for the association of accessory proteins in the RNA-directed DNA methylation (RdDM) pathway. Various components have been uncovered that are involved in the process of DNA methylation, but it is still not clear how the transcription of Pol V is regulated. Here, we report that the conserved RNA polymerase II (Pol II) elongator, SPT6L, binds to thousands of intergenic regions in a Pol II-independent manner. The intergenic enrichment of SPT6L, interestingly, co-occupies with the largest subunit of Pol V (NRPE1) and mutation of SPT6L leads to the reduction of DNA methylation but not Pol V enrichment. Furthermore, the association of SPT6L at Pol V loci is dependent on the Pol V associated factor, SPT5L, rather than the presence of Pol V, and the interaction between SPT6L and NRPE1 is compromised in spt5l. Finally, Pol V RIP-seq reveals that SPT6L is required to maintain the amount and length of Pol V transcripts. Our findings thus uncover the critical role of a Pol II conserved elongator in Pol V mediated DNA methylation and transcription, and shed light on the mutual regulation between Pol V and II in plants.

Abstract Background Understanding factors associated with antiretroviral treatment (ART) adherence is crucial for ART success among people living with HIV (PLHIV) in the “test and treat” era. Multiple psychosocial factors tend to coexist and have a syndemic effect on ART adherence. We aimed to explore factors associated with ART adherence and the syndemic effect of multiple psychosocial factors on ART adherence among PLHIV newly starting ART in Guangdong Province, China. Methods Newly diagnosed PLHIV from six cities in Guangdong Province were recruited between May 2018 and June 2019, and then followed up from May 2019 to August 2020. Baseline and follow-up data were collected from a questionnaire and the national HIV surveillance system, the follow-up data of which were analyzed in this study. A Center for Adherence Support Evaluation (CASE) index > 10 points was defined as optimal ART adherence, which was measured via participants’ self-reported adherence during follow-up survey. Multivariable logistic regression was used to identify factors associated with ART adherence. Exploratory factor analysis (EFA) and multi-order latent variable structural equation modeling (SEM) were performed to explore the syndemic effect of multiple psychosocial factors on ART adherence. Results A total of 734 (68.53%) follow-up participants were finally included in this study among the 1071 baseline participants, of whom 91.28% (670/734) had self-reported optimal ART adherence. Unemployment (aOR = 1.75, 95%CI: 1.01–3.02), no medication reminder (aOR = 2.28, 95%CI: 1.09–4.74), low medication self-efficacy (aOR = 2.28, 95%CI: 1.27–4.10), low social cohesion (aOR = 1.82, 95%CI: 1.03–3.19), no social participation (aOR = 5.65, 95%CI: 1.71–18.63), and ART side effects (aOR = 0.46, 95%CI: 0.26–0.81) were barriers to optimal ART adherence. The EFA and second-order latent variable SEM showed a linear relationship (standardized coefficient = 0.43, P

Purpose: To study the clinical effectiveness of the topical application of tranexamic acid in hand tendon release. Methods: This was a randomized controlled trial conducted after receiving approval from the local ethics committee according to guidelines from the Helsinki Declaration. Eighty patients who underwent hand tendon release operation in our hospital from January 2021 to December 2022 were included and randomly divided into 2 groups. Patients in the tranexamic acid group (40 cases) received intraoperative topical application of 2 g of tranexamic acid after tendon release, while patients in the conventional group (40 cases) did not receive topical application of tranexamic acid during operation. The operation time, perioperative hemoglobin changes, total blood loss, incidence of early postoperative complications, and total active movement (TAM) before surgery and 6 months after surgery were compared between the 2 groups. The continuous variable which follows normal distribution expressed by mean ± SD and used t-test to compare between groups. Meanwhile, categorical variables were used by Chi-square test, and a p

Abstract Rapid and accurate detection of respiratory virus aerosols is highlighted for virus surveillance and infection control. Here, we report a wireless immunoassay technology for fast (within 10 min), on-site (wireless and battery-free), and sensitive (limit of detection down to fg/L) detection of virus antigens in aerosols. The wireless immunoassay leverages the immuno-responsive hydrogel-modulated radio frequency resonant sensor to capture and amplify the recognition of virus antigen, and flexible readout network to transduce the immuno bindings into electrical signals. The wireless immunoassay achieves simultaneous detection of respiratory viruses such as severe acute respiratory syndrome coronavirus 2, influenza A H1N1 virus, and respiratory syncytial virus for community infection surveillance. Direct detection of unpretreated clinical samples further demonstrates high accuracy for diagnosis of respiratory virus infection. This work provides a sensitive and accurate immunoassay technology for on-site virus detection and disease diagnosis compatible with wearable integration.

Abstract Suppressing random noise in seismic signals is an important issue in research on processing seismic data. Such data are difficult to interpret because seismic signals usually contain a large amount of random noise. While denoising can be used to reduce noise, most denoising methods require the prior estimation of the threshold of the signals to handle random noise, which makes it difficult to ensure optimal results. In this paper, we propose a wavelet threshold-based method of denoising that uses the improved chaotic fruit fly optimization algorithm. Our method of selects uses generalized cross-validation as the objective function for threshold selection. This objective function is optimized by introducing an adjustment coefficient to the chaotic fruit fly optimization algorithm, and the optimal wavelet threshold can then be obtained without any prior information. We conducted denoising tests by using synthetic seismic records and empirical seismic data acquired from the field. We added three types of noise, with different average signal-to-noise ratios, to synthetic seismograms containing noise with original intensities of − 5, − 1, and 4 dB, respectively. The results showed that after denoising, the signal-to-noise ratios of the three types of noise increased to 7.12, 10.04, and 14.26, while the mean-squared errors in the results of the proposed algorithm decreased to 0.006, 0.0031, and 0.0012, respectively.

Abstract In order to solve the safety and efficiency problems in the picking process of Waxberry, the slow speed and low precision of high‐density Waxberry target detection under a complex background were studied. A lightweight Waxberry target detection algorithm based on YOLOv5 is studied. In this study, C3‐Faster1 and C3‐Faster2 modules are proposed, which are located in the backbone and neck of the network: C3‐Faster1 can improve the model speed with a simple structure; C3‐Faster2 integrates the context attention mechanism and transform module based on C3‐Faster1 to make the network pay attention to the information of Waxberry image context and expand the channel receptive field. A new pyramid module, SPPFCSPC, is proposed to expand the sensing field and improve the accuracy of boundary detection. It also combines the Coordinate Attention (CA) and Dyhead dynamic detection head to suppress useless information and enhance the detection ability of small targets. Compared to YOLOv4, YOLOv7, and YOLOv8, mean accuracy percentage (mAP) improved by 5.7%, 9.4%, 8.3%. Compared to the base YOLOv5 model, mAP has improved from 86.5% to 91.9%, running on 2 GB Jeston nano, and the improved model is 5.03 frames per second (FPS) faster than YOLOv5. Experiments show that the designed module is more effective in Waxberry detection tasks.

Abstract Tomatoes possess significant nutritional and economic value. However, frequent diseases can detrimentally impact their quality and yield. Images of tomato diseases captured amidst intricate backgrounds are susceptible to environmental disturbances, presenting challenges in achieving precise detection and identification outcomes. This study focuses on tomato disease images within intricate settings, particularly emphasizing four prevalent diseases (late blight, gray leaf spot, brown rot, and leaf mold), alongside healthy tomatoes. It addresses challenges such as excessive interference, imprecise lesion localization for small targets, and heightened false-positive and false-negative rates in real-world tomato cultivation settings. To address these challenges, we introduce a novel method for tomato disease detection named TomatoDet. Initially, we devise a feature extraction module integrating Swin-DDETR’s self-attention mechanism to craft a backbone feature extraction network, enhancing the model’s capacity to capture details regarding small target diseases through self-attention. Subsequently, we incorporate the dynamic activation function Meta-ACON within the backbone network to further amplify the network’s ability to depict disease-related features. Finally, we propose an enhanced bidirectional weighted feature pyramid network (IBiFPN) for merging multi-scale features and feeding the feature maps extracted by the backbone network into the multi-scale feature fusion module. This enhancement elevates detection accuracy and effectively mitigates false positives and false negatives arising from overlapping and occluded disease targets within intricate backgrounds. Our approach demonstrates remarkable efficacy, achieving a mean Average Precision (mAP) of 92.3% on a curated dataset, marking an 8.7% point improvement over the baseline method. Additionally, it attains a detection speed of 46.6 frames per second (FPS), adeptly meeting the demands of agricultural scenarios.

Genetic factors play significant roles in the tumorigenicity of lung cancer; however, there is lack of systematic and large‐scale characterization of pathogenic germline variants for lung cancer. In this study, germline variants in 146 preselected cancer‐susceptibility genes were detected in 17 904 Chinese lung cancer patients by clinical next‐generation sequencing. Among 17 904 patients, 1738 patients (9.7%) carried 1840 pathogenic/likely pathogenic (P/LP) variants from 87 cancer‐susceptibility genes. SBDS (SBDS ribosome maturation factor) (1.37%), TSHR (thyroid stimulating hormone receptor) (1.20%), BLM (BLM RecQ like helicase) (0.62%), BRCA2 (BRCA2 DNA repair associated) (0.62%), and ATM (ATM serine/threonine kinase) (0.45%) were the top five genes with the highest overall prevalence. The top mutated pathways were all involved in DNA damage repair (DDR). Case–control analysis showed SBDS c.184A>T(p.K62*), TSHR c.1574T>C(p.F525S), BRIP1 (BRCA1 interacting helicase 1) c.1018C>T(p.L340F), and MUTYH (mutY DNA glycosylase) c.55C>T(p.R19*) were significantly associated with increased lung cancer risk (q value

To study the effects of hot air temperature and slice thickness on the drying characteristics, physicochemical properties and antioxidant components of Mulusasiatica Nakai slices. The Mulusasiatica Nakai slices with thickness of 3 mm and 5 mm were dried in the hot air temperature range of 60, 70, 80, 90 ℃. Five classical food thin layer drying models were used to nonlinear fit the experimental data, and the diffusion coefficient and activation energy were calculated. The color, hardness, rehydration properties and antioxidant components of the dried slices were analyzed. Results showed that, the drying time was obviously shortened with the increase of hot-air temperature and the decrease of slice thickness. In the experimental drying temperature range, the effective diffusion coefficient increased with the increase of temperature. The activation energies were 17.46 kJ/mol and 23.82 kJ/mol when the slice thickness was 3 and 5 mm, respectively. Fick diffusion model was used to describe the evaporation process of Mulusasiatica Nakai slices. Compared with other models, Page model could better fit the drying process of Mulusasiatica Nakai slices. When the slice thickness was 3 mm and the hot-air temperature was 90 ℃, the dried product was light yellow, with high rehydration performance and low hardness. In terms of antioxidant retention, heat lost about 50% of ascorbic acid, but only about 35% of total phenolics. In conclusion, the slice thickness could be selected to be 3mm, the hot air temperature 90 ℃ for drying, drying time 90 min, dried product color was light yellow, higher rehydration performance, lower hardness, and could better retain the antioxidant components in Mulusasiatica Nakai.

In the recycling process, aluminum scraps, characterized by a considerable specific surface area, yield a remelt abundant in inclusions. While advanced melt purification systems proficiently extract hydrogen and large inclusions, micron-sized inclusions remain challenging to remove. Despite previous findings suggesting nominal effects of inclusions on the microstructure and properties of aged 7xxx-series plates, the products' airworthiness demands further improvement. This research aims to decipher the influence of micron-sized inclusions on the microstructure and properties of recycled 7xxx aluminum alloy. We prepared thin sheets of varied cleanliness and utilized SEM, EBSD, and TEM to characterize their microstructure at different heat treatment stages. Additionally, high-temperature tensile and bending properties, together with exfoliation corrosion behaviors, were examined. Our results point to the causative role of inclusions in localized dislocation accumulation post-rolling, which annealing can mitigate but not fully eliminate; however, a solid solution can effectively address this issue. The inclusions significantly disrupt the microstructure and properties of the annealed recycled sheet, but their impact on the solid solution-aged recycled sheet is minor. This study's findings can guide the high-end transformation of recycled aluminum alloy and lay a theoretical foundation for sustainable aluminum recycling.

Plant height influences plant architecture, lodging resistance, and yield performance. It is modulated by gibberellic acid (GA) metabolism and signaling. DELLA proteins, acting as central repressors of GA signaling, integrate various environmental and hormonal signals to regulate plant growth and development in Arabidopsis. We examined the role of two DELLA proteins, GmRGAa and GmRGAb, in soybean plant height control. Knockout of these proteins led to longer internodes and increased plant height, primarily by increasing cell elongation. GmRGAs functioned under different light conditions, including red, blue, and far-red light, to repress plant height. Interaction studies revealed that GmRGAs interacted with the blue light receptor GmCRY1b. Consistent with this, GmCRY1b partially regulated plant height via GmRGAs. Additionally, DELLA proteins were found to stabilize the protein GmSTF1/2, a key positive regulator of photomorphogenesis. This stabilization led to increased transcription of GmGA2ox-7b and subsequent reduction in plant height. This study enhances our understanding of DELLA-mediated plant height control, offering Gmrgaab mutants for soybean structure and yield optimization.

The emerging viruses within the genus Henipavirus in the family Paramyxoviridae pose a great threat to public biosafety. To develop a quadruple real-time fluorescence-based quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay is pivotal for the early warning of the potential of zoonotic infectious diseases. Specific primers and probes were designed for the relatively conserved regions based on whole genome sequences of Langya virus (LayV), Mojiang virus (MojV), Nipah virus (NiV), and Cedar virus (CedV), followed by the establishment of a quadruple real-time fluorescence-based qRT-PCR detection method. No cross-reactivity was observed with other viral nucleic acids. The optimal linear detection range for LayV, MojV, NiV, and CedV was 101-108 copies/μL, and the lower limit of detection was 10 copies/μL. Three different DNA concentrations of LayV, MojV, NiV, and CedV (104, 105, and 106 copies/μL) were tested 14 times, achieving good repeatability. The standard deviation of the cycle threshold values for each concentration was 90 %, and the correlation coefficient was >0.99. The established quadruple real-time fluorescence-based qRT-PCR assay for the detection of LayV, MojV, NiV, and CedV exhibits good sensitivity, specificity, and repeatability. Therefore, it can be used to detect Henipavirus and other related clinical specimens.

Abstract The ball screw pair is a precision drive component that converts rotary motion into linear motion. In practical applications, because the feed system usually has rotational torque and geometric errors, it may increase the contact load of the ball screw pair and reduce the fatigue life. In order to study the influence of different loads and geometric errors on the maximum contact load and fatigue life of ball screw pairs, the following research work was carried out. Firstly, based on the composite load and rotational torque, the ball load distribution model is established, and the accuracy of the model is verified by finite element modeling analysis. Then, the influence of different composite loads, rotation times and geometric errors (including ball size error, lead error and raceway tooth profile error) on the ball load distribution is analyzed. Finally, the influence of compound load, rotating torque and geometric error on the fatigue life of ball screw pairs is studied. The results show that the rotational torque and lead error have a great influence on the load distribution and fatigue life of the ball, and the influence of lead error on load distribution is greater than that of dimension error and tooth profile error. The fatigue life of the ball screw pair with non-uniform load distribution is shorter than that of the ball screw pair with uniform load distribution.

This research investigated the fixed-time (FXT) synchronization of fractional-order fuzzy cellular neural networks (FCNNs) with delays and interactions based on an enhanced FXT stability theorem. By conceiving proper Lyapunov functions and applying inequality techniques, several sufficient conditions were obtained to vouch for the fixed-time synchronization (FXTS) of the discussed systems through two categories of control schemes. Moreover, in terms of another FXT stability theorem, different upper-bounding estimating formulas for settling time (ST) were given, and the distinctions between them were pointed out. Two examples were delivered at length to demonstrate the conclusions.

Abstract Immune checkpoint inhibitors targeting the programmed cell death-1 (PD-1) protein significantly improve survival in patients with advanced non-small-cell lung cancer (NSCLC), but its impact on early-stage ground-glass opacity (GGO) lesions remains unclear. This is a single-arm, phase II trial (NCT04026841) using Simon’s optimal two-stage design, of which 4 doses of sintilimab (200 mg per 3 weeks) were administrated in 36 enrolled multiple primary lung cancer (MPLC) patients with persistent high-risk (Lung-RADS category 4 or had progressed within 6 months) GGOs. The primary endpoint was objective response rate (ORR). T/B/NK-cell subpopulations, TCR-seq, cytokines, exosomal RNA, and multiplexed immunohistochemistry (mIHC) were monitored and compared between responders and non-responders. Finally, two intent-to-treat (ITT) lesions (pure-GGO or GGO-predominant) showed responses (ORR: 5.6%, 2/36), and no patients had progressive disease (PD). No grade 3–5 TRAEs occurred. The total response rate considering two ITT lesions and three non-intent-to-treat (NITT) lesions (pure-solid or solid-predominant) was 13.9% (5/36). The proportion of CD8+ T cells, the ratio of CD8+/CD4+, and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time. Correspondingly, the mIHC analysis showed more CD8+ T cells infiltrated in responders. Besides, responders’ cytokine concentrations of EGF and CTLA-4 increased during treatment. The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders. Collectively, PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns. Such effects were associated with specific T-cell re-distribution, EGF/CTLA-4 cytokine compensation, and regulation of metabolism pathways.

Abstract Antibiotic resistance has garnered significant attention due to the scarcity of new antibiotics in development. Protoporphyrin IX (PpIX)-mediated photodynamic therapy shows promise as a novel antibacterial strategy, serving as an alternative to antibiotics. However, the poor solubility of PpIX and its tendency to aggregate greatly hinder its photodynamic efficacy. In this study, we demonstrate that alkylated EDTA derivatives (aEDTA), particularly C14-EDTA, can enhance the solubility of PpIX by facilitating its dispersion in aqueous solutions. The combination of C14-EDTA and PpIX exhibits potent antibacterial activity against Staphylococcus aureus (S. aureus) when exposed to LED light irradiation. Furthermore, this combination effectively eradicates S. aureus biofilms, which are known to be strongly resistant to antibiotics, and demonstrates high therapeutic efficacy in an animal model of infected ulcers. Mechanistic studies reveal that C14-EDTA can disrupt PpIX crystallization, increase bacterial membrane permeability and sequester divalent cations, thereby improving the accumulation of PpIX in bacteria. This, in turn, enhances reactive oxygen species (ROS) production and the antibacterial photodynamic activity. Overall, this effective strategy holds great promise in combating antibiotic-resistant strains. Graphical Abstract

Abstract Internal N6-methyladenosine (m6A) modifications are among the most abundant modifications of messenger RNA, playing a critical role in diverse biological and pathological processes. However, the functional role and regulatory mechanism of m6A modifications in the immune response to Mycobacterium tuberculosis infection remains unknown. Here, we report that methyltransferase-like 14 (METTL14)-dependent m6A methylation of NAPDH oxidase 2 (Nox2) mRNA was crucial for the host immune defense against M. tuberculosis infection and that M. tuberculosis-secreted antigen EsxB (Rv3874) inhibited METTL14-dependent m6A methylation of Nox2 mRNA. Mechanistically, EsxB interacted with p38 MAP kinase and disrupted the association of TAB1 with p38, thus inhibiting the TAB1-mediated autophosphorylation of p38. Interaction of EsxB with p38 also impeded the binding of p38 with METTL14, thereby inhibiting the p38-mediated phosphorylation of METTL14 at Thr72. Inhibition of p38 by EsxB restrained liquid–liquid phase separation (LLPS) of METTL14 and its subsequent interaction with METTL3, preventing the m6A modification of Nox2 mRNA and its association with the m6A-binding protein IGF2BP1 to destabilize Nox2 mRNA, reduce ROS levels, and increase intracellular survival of M. tuberculosis. Moreover, deletion or mutation of the phosphorylation site on METTL14 impaired the inhibition of ROS level by EsxB and increased bacterial burden or histological damage in the lungs during infection in mice. These findings identify a previously unknown mechanism that M. tuberculosis employs to suppress host immunity, providing insights that may empower the development of effective immunomodulators that target M. tuberculosis.

Abstract P. ginseng is a precious traditional Chinese functional food, which is used for both medicinal and food purposes, and has various effects such as immunomodulation, anti-tumor and anti-oxidation. The growth year of P. ginseng has an important impact on its medicinal and economic values. Fast and nondestructive identification of the growth year of P. ginseng is crucial for its quality evaluation. In this paper, we propose a FC-CNN network that incorporates spectral and spatial features of hyperspectral images to characterize P. ginseng from different growth years. The importance ranking of the spectra was obtained using the random forest method for optimal band selection. Based on the hyperspectral reflectance data of P. ginseng after radiometric calibration and the images of the best five VNIR bands and five SWIR bands selected, the year-by-year identification of P. ginseng age and its identification experiments for food and medicinal purposes were conducted, and the FC-CNN network and its FCNN and CNN branch networks were tested and compared in terms of their effectiveness in the identification of P. ginseng growth years. It has been experimentally verified that the best year-by-year recognition was achieved by utilizing images from five visible and near-infrared important bands and all spectral curves, and the recognition accuracy of food and medicinal use reached 100%. The FC-CNN network is significantly better than its branching model in the effect of edible and medicinal identification. The results show that for P. ginseng growth year identification, VNIR images have much more useful information than SWIR images. Meanwhile, the FC-CNN network utilizing the spectral and spatial features of hyperspectral images is an effective method for the identification of P. ginseng growth year.

Abstract Background Despite the importance of medication adherence in treatment effectiveness, little is known about the association between medication non-adherence and self-inflicted violence behaviors. We aimed to assess whether medication non-adherence increased the risk of self-inflicted violence behaviors among schizophrenics in communities (hypothesis 1) and whether the dose–response relationship existed (hypothesis 2). Methods This 12-year cohort study in western China recruited 292,667 community-dwelling schizophrenics. The proportion of regular medication (PRM) was calculated by dividing the time of “regular adherence” by the total time of antipsychotic treatment during follow-up period as an indicator of medication adherence. For hypothesis 1, medication adherence was designated as a binary variable with a threshold of 0.8 (PRM); for hypothesis 2, medication adherence was specified as five-category and continuous variables, respectively. Inverse probability weighting and mixed effects Cox proportional hazards models were conducted for confounders control and survival analyses. Results One hundred eighty-five thousand eight hundred participants were eligible for the final analyses, with a mean age of 47.49 years (SD 14.55 years), of whom 53.6% were female. For hypothesis 1, the medication non-adherence group (PRM

Abstract Background This study examined the association between chest muscles and chronic obstructive pulmonary disease (COPD) and the relationship between chest muscle areas and acute exacerbations of COPD (AECOPD). Methods There were 168 subjects in the non-COPD group and 101 patients in the COPD group. The respiratory and accessory respiratory muscle areas were obtained using 3D Slicer software to analysis the imaging of computed tomography (CT). Univariate and multivariate Poisson regressions were used to analyze the number of AECOPD cases during the preceding year. The cutoff value was obtained using a receiver operating characteristic (ROC) curve. Results We scanned 6342 subjects records, 269 of which were included in this study. We then measured the following muscle areas (non-COPD group vs. COPD group): pectoralis major (19.06 ± 5.36 cm2 vs. 13.25 ± 3.71 cm2, P

Abstract Background/Aim With the pharmaceutical innovation and clinical knowledge updating, the continuing education and on-the-job training are extremely important for improving community pharmacists’ professional competence. Previous training often adopted traditional lecture-based teaching, and the efficacy was limited. The aim of this study is to develop a new strategy for community pharmacist training. Methods Based on the BOPPPS (Bridge-in, Objective, Pre-assessment, Participatory Learning, Post-assessment and Summary) teaching model and workshop method, a continuing on-the-job training program was constructed. Participates were randomly and evenly divided into two groups by random number table method. Twenty-four community pharmacists in total completed all training contents and evaluation components in this study. Twelve pharmacists in experimental group were trained via this new BOPPPS-based workshop, while others still adopted traditional didactic lecture-based approaches. Results After training, quantitative examination combined with clinical pharmacy practice tests were carried out to evaluate the effectiveness and outcomes of two training groups. For written exam, the total scores from the BOPPPS-based workshop group (82.67 ± 4.70) was higher than that of traditional lectured-base group (73.75 ± 6.15) (P

Abstract Background Malignant mesothelioma is a type of infrequent tumor that is substantially related to asbestos exposure and has a terrible prognosis. We tried to produce a fibroblast differentiation-related gene set for creating a novel classification and prognostic prediction model of MESO. Method Three databases, including NCBI-GEO, TCGA, and MET-500, separately provide single-cell RNA sequencing data, bulk RNA sequencing profiles of MESO, and RNA sequencing information on bone metastatic tumors. Dimensionality reduction and clustering analysis were leveraged to acquire fibroblast subtypes in the MESO microenvironment. The fibroblast differentiation-related genes (FDGs), which were associated with survival and subsequently utilized to generate the MESO categorization and prognostic prediction model, were selected in combination with pseudotime analysis and survival information from the TCGA database. Then, regulatory network was constructed for each MESO subtype, and candidate inhibitors were predicted. Clinical specimens were collected for further validation. Result A total of six fibroblast subtypes, three differentiation states, and 39 FDGs were identified. Based on the expression level of FDGs, three MESO subtypes were distinguished in the fibroblast differentiation-based classification (FDBC). In the multivariate prognostic prediction model, the risk score that was dependent on the expression level of several important FDGs, was verified to be an independently effective prognostic factor and worked well in internal cohorts. Finally, we predicted 24 potential drugs for the treatment of MESO. Moreover, immunohistochemical staining and statistical analysis provided further validation. Conclusion Fibroblast differentiation-related genes (FDGs), especially those in low-differentiation states, might participate in the proliferation and invasion of MESO. Hopefully, the raised clinical subtyping of MESO would provide references for clinical practitioners.

Abstract Background Knee osteoarthritis (KOA) is a highly disabling disease, and studying its progression is crucial. However, it is still unclear whether the progression of ipsilateral knee osteoarthritis is influenced by contralateral knee osteoarthritis. Methods Data were collected from the OAI database and divided into two study cohorts (right/left KOA cohort). Each cohort had a target knee (right/left knee) and was further divided into two groups (exposure/control group). The demographic data of both cohorts were balanced at baseline by propensity score matching (PSM), and the data included rating scale and radiographic and clinical data. After checking for balance in the matched variables, we then compared the differences between the two groups in each cohort. Our primary focus was on the minimum joint space width (mJSW) of the target knee, which was measured four years after baseline. The secondary outcome was the arthroplasty rate of the target knee within nine years. Results In this study, a total of 678 participants were enrolled and matched. After 1:1 PSM of the baseline demographic data, 98 participants in the right KOA cohort (RKOAC) were successfully matched, and 117 participants in the left KOA cohort (LKOAC) were successfully matched. Furthermore, the standardized mean difference (SMD) of the matched variables in both cohorts was less than 0.25. After analyzing the outcome metrics, we found that the target knee had a significantly lower mJSW in the fourth year after baseline and a significantly greater arthroplasty rate within nine years in the exposed group than in the control group. RKOAC: mJSW (exposure: 2.6(1.1 ~ 3.6) vs. control: 3.3(2.0 ~ 4.2), P

The chloride natural diffusion (CND) test is often used in concrete-related field to analyze the chloride diffusion behavior in concrete and chloride diffusion coefficient (D(Chloride)) is an important parameter for durability assessment of RC structures. Thus, CND and iodide natural diffusion (IND) tests were performed to obtain the diffusion depth and concentration and D(Chloride)/D(Iodide) in concrete with different mineral admixture types and dosage to verify the feasibility of IND to replace the CND test under condition that some concrete exposed in marine environment. It is found that IND test need to conduct under air-isolated dark environments with lower iodide oxidative behavior effectively. Besides, with the increase of FA amount, the concentration of chloride/iodide decreased and then increased, while the chloride/iodide binding capacity increased and then decreased. However, with the increase of GGBFS content, the chloride/iodide concentration gradually decreased, while the chloride/iodide binding capacity increased. Meanwhile, a good linear relationship was shown between the free ion concentration and bound ion concentration. Although the chloride or iodide diffused into the concrete can prompt the generation of complex compounds, namely 3CaO·Al2O3·CaCl2·10H2O and 3CaO·Al2O3·CaI2·8H2O, iodide seems to hinder secondary hydration of FA/GGBFS and lower the compactness of matrix and increase the proportion of harmful gels, compared to chloride. With the increase of mineral admixture dosage, there are more hydrates, the porosity gradually decreases, and the proportion of harmful pores also drops. Moreover, a quadratic relationship between D (Chloride) and D (Iodide) was studied, a direct correlation between FA/GGBFS dosage and conversion coefficient was given, and there is a plane function relationship between D(Chloride)/D(Iodide) and total porosity, FA/GGBFS dosage. Overall, this study gives a new idea of IND replacing CND test to assess the durability of RC marine structures.

Background: Existing research has provided evidence of changes in hepatitis delta virus (HDV) prevalence worldwide. This study aimed to investigate the prevalence and molecular characteristics of HDV to elucidate its spread in China. Methods: A total of 3,000 samples were collected from 2,241 HBV monoinfections and 759 HBV/HIV-1 coinfections across 13 sites in northern, southern, western, and southwestern China. Serological and virological prevalence were determined by detecting anti-HDV antibodies and HDV RNA. Results: The study revealed a 2.63% (95% CI: 2.06–3.21) seroprevalence of HDV among HBV infections in China, exhibiting regional variation. HDV seroprevalence was notably higher at 7.91% (95% CI: 5.98–9.83) in HBV and HIV-1 coinfections. Region and HIV-1 infection were identified as risk factors for HDV infection. Virological prevalence was 0.67% (95% CI: 0.38–0.96) in HBV infections and 2.24% (95% CI: 1.18–3.29) in HBV/HIV-1 coinfections. The predominant HDV genotype in China was HDV-2a, followed by HDV-1. Participants with anti-HDV positivity demonstrated significantly higher proportions of abnormal liver dysfunction and elevated HBV DNA load (P < 0.001) compared to anti-HDV-negative participants. Conclusions: This study highlights the HDV epidemic in China, sheds light on its geographical distribution and high-risk populations, and provides insights for developing strategies to manage the spread of HDV in the country.

Neoadjuvant therapy followed by surgery is a common clinical strategy for operable non-small cell lung cancer (NSCLC), and the mainstream neoadjuvant therapies include chemoimmunotherapy, targeted therapy, and chemotherapy. However, there is a lack of studies to report the difference in benefits between these treatment modalities in the same institution. Therefore, this study aimed to depict the short-term efficacy of radiology and pathology achieved by different therapies and their impact on long-term survival as well as the underlying clinical significance. A total of 243 NSCLC patients who underwent different neoadjuvant therapies were eligible for inclusion. Demographic, radiological, and pathological features of patients were recorded. The event-free survival (EFS) outcome was analyzed using Kaplan-Meier analysis. The objective response rates (ORR) of primary tumor in the chemoimmunotherapy, targeted therapy, and chemotherapy cohorts were 48.95 %, 57.58 %, and 34.09 % respectively, major pathological response (MPR) rates were 58.74 %, 15.15 %, and 20.83 % (P

All-solid-state lithium batteries (ASSLB) utilizing solid polymer electrolytes (SPEs) are attractive due to the enhanced safety and processability. However, operation of the cells usually requires elevated temperatures to overcome the low ionic conductivity or high interfacial resistance issue. Through this study, we identify that grain boundaries within SPE exist and play a crucial role on Li-ion transport and cell performance. Accordingly, a direct hot-press activation approach was proposed and demonstrated significant reduction of boundary resistance within the SPE, leading to a fourfold increase in room temperature (r.t.) ionic conductivity. The detailed morphological and structural study suggest a pressure-induced amorphization mechanism for the activation of room-temperature SPE. Through this facile activation procedure, all solid-state LiFeO4 (LFP)|SPE|Li cells demonstrate improved performance for both high specific capacity and stable cycling at r.t.

Efficient and accurate wind power prediction is crucial for enhancing the reliability and safety of power system. The data-driven forecasting methods are regarded as an effective solution. However, the inherent randomness and nonlinearity of wind power systems, along with the abundance of redundant information in measurement data, present challenges to forecasting methods. The integration of precise and efficient techniques for data feature decomposition and extraction is essential in conjunction with advanced data-driven forecasting models. Focus on the seasonal variation characteristics of wind energy, a hybrid wind power prediction model based on seasonal feature decomposition and enhanced feature extraction is proposed. The effectiveness and superiority of the proposed method in predictive accuracy are demonstrated through comprehensive multi-model experiment comparisons.

Background The prognosis of patients with coronary artery disease is adversely affected by elevated fasting plasma glucose (FPG) levels. However, the relationship between FPG levels and in-hospital cardiac arrest (IHCA) remains unclear.Objectives The objective of this study was to investigate the association between FPG levels and IHCA in patients diagnosed with acute coronary syndrome (ACS).Methods Data from a total of 31,726 ACS patients fitted with inclusion and exclusion criteria across 241 hospitals in the Improving Care for Cardiovascular Disease in China-ACS project from November 2014 to July 2019 were collected. Different logistic regression models were utilized to examine the associations of FPG levels with IHCA. Sensitivity analyses were then conducted to assess the robustness of the findings. Marginal effect analyses were also employed to evaluate the impact of different therapies.Results A total of 335 cases of IHCA and 293 in-hospital mortality were recorded throughout the study. A non-linear relationship between FPG levels and IHCA was identified after adjusting for the covariates. Specifically, a significant association was found between elevated FPG levels (≥6.1 mmol/L) and an increased risk of IHCA. These findings remained consistent across different subgroup analyses including both the diabetic and non-diabetic patients. Additionally, the marginal effect analyses revealed that percutaneous coronary intervention could lower the high FPG-related risk.Conclusions The study findings showed a positive correlation between FPG levels and a higher incidence of IHCA, irrespective of the presence of diabetes.

ABSTRACTGliomas are the most common type of primary brain tumor. Despite advances in treatment, it remains one of the most aggressive and deadly tumor of the central nervous system (CNS). Gliomas are characterized by high malignancy, heterogeneity, invasiveness, and high resistance to radiotherapy and chemotherapy. It is urgent to find potential new molecular targets for glioma. The TRPM channels consist of TRPM1-TPRM8 and play a role in many cellular functions, including proliferation, migration, invasion, angiogenesis, etc. More and more studies have shown that TRPM channels can be used as new therapeutic targets for glioma. In this review, we first introduce the structure, activation patterns, and physiological functions of TRPM channels. Additionally, the pathological mechanism of glioma mediated by TRPM2, 3, 7, and 8 and the related signaling pathways are described. Finally, we discuss the therapeutic potential of targeting TRPM for glioma.

ABSTRACTHousehold contacts (HHCs) of patients with active tuberculosis (ATB) are at higher risk of Mycobacterium tuberculosis (M. tuberculosis) infection. However, the immune factors responsible for different defense responses in HHCs are unknown. Hence, we aimed to evaluate transcriptome signatures in human peripheral blood mononuclear cells (PBMCs) of HHCs to aid risk stratification. We recruited 112 HHCs of ATB patients and followed them for 6 years. Among the HHCs, only 2 developed ATB, while the remaining HHCs were classified into three groups: (1) HHC-1 group (n = 23): HHCs with consistently positive T-SPOT.TB test, negative chest radiograph, and no clinical symptoms or evidence of ATB during the 6-year follow-up period; (2) HHC-2 group (n = 15): HHCs with an initial positive T-SPOT result that later became negative without evidence of ATB; (3) HHC-3 group (n = 14): HHCs with a consistently negative T-SPOT.TB test and no clinical or radiological evidence of ATB. HHC-2 and HHC-3 were combined as HHC-23 group for analysis. RNA sequencing (RNA-seq) in PBMCs, with and without purified protein derivative (PPD) stimulation, identified significant differences in gene signatures between HHC-1 and HHC-23. Gene ontology analysis revealed functions related to bacterial pathogens, leukocyte chemotaxis, and inflammatory and cytokine responses. Modules associated with clinical features in the HHC-23 group were linked to the IL-17 signaling pathway, ferroptosis, complement and coagulation cascades, and the TNF signaling pathway. Validation using real-time PCR confirmed key genes like ATG-7, CXCL-3, and TNFRSF1B associated with infection outcomes in HHCs. Our research enhances understanding of disease mechanisms in HHCs. HHCs with persistent latent tuberculosis infection (HHC-1) showed significantly different gene expression compared to HHCs with no M. tuberculosis infection (HHC-23). These findings can help identify HHCs at risk of developing ATB and guide targeted public health interventions.

For batch time-varying processeswith non-repetitive disturbances, a cross-coupling indirect iterative learning control (CC-iILC) is proposed. The set trajectory of the system on the single axis is accurately tracked by an indirect iterative learning control strategy with a PI controller for its time direction and a closed-loop feedback control strategy for the batch direction. Under the asymptotically stable condition of the two-dimensional (2D) dynamic model, the optimal control law is obtained by optimizing the H-infinity control function. To avoid the contour error during coupling, the cross-coupling technique is used to distribute the contour error to each axis for compensation. The stability condition of the indirect iterative learning controller is analyzed by a two-dimensional Fornasini-Marchesini (FM) batch dynamics model and two-dimensional robust H-infinity control theory. The feasibility and superiority of the proposed control method are verified by numerical simulation and experimental tests.

Bipolar disorder (BD) is a severe psychiatric disease with high rates of misdiagnosis and underdiagnosis, resulting in a significant disease burden on both individuals and society. Abnormal neural oscillations have garnered significant attention as potential neurobiological markers of BD. However, untangling the mechanisms that subserve these baseline alternations requires measurement of their electrophysiological underpinnings. This systematic review investigates consistent abnormal resting-state EEG power of BD and conducted an initial exploration into how methodological approaches might impact the study outcomes. This review was conducted in Pubmed-Medline and Web-of-Science in March 2024 to summarize the oscillation changes in resting-state EEG (rsEEG) of BD. We focusing on rsEEG to report spectral power in different frequency bands. We identified 10 studies, in which neural oscillations was compared with healthy individuals (HCs). We found that BD patients had abnormal oscillations in delta, theta, beta, and gamma bands, predominantly characterized by increased power, indicating potential widespread neural dysfunction, involving multiple neural networks and cognitive processes. However, the outcomes regarding alpha oscillation in BD were more heterogeneous, which is thought to be potentially influenced by the disease severity and the diversity of samples. Furthermore, we conducted an initial exploration into how demographic and methodological elements might impact the study outcomes, underlining the importance of implementing standardized data collection methods. Key aspects we took into account included gender, age, medication usage, medical history, the method of frequency band segmentation, and situation of eye open/eye close during the recordings. Therefore, in the face of abnormal multiple oscillations in BD, we need to adopt a comprehensive research approach, consider the multidimensional attributes of the disease and the heterogeneity of samples, and pay attention to the standardized experimental design to improve the reliability and reproducibility of the research results.