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Growth differentiation factor-15 (GDF-15), a member of the transforming growth factor (TGF-β) superfamily, and is expressed and secreted in response to inflammation, oxidative stress and hypoxia. It has been shown in several studies to be a predictor of heart failure. However, the only kits available on the market are ELISA kits, which are costly and error-prone and are not conducive for clinical use. Here, we developed a chemiluminescence kit which optimized the reaction conditions and the reaction time was reduced to 10 min. We further proved that it can be used to measure GDF-15 in serum or plasma accurately and fastly, and provide additional information for the diagnosis of heart failure disease. Methodological comparison and clinical study verified this method is a reliable, economical and highly automated blood test method. • All necessary steps and the reagents needed are provided. • Reliability of the chemiluminescence immunoassay was verified by analyzing serum GDF-15 levels from different groups. • GDF-15 can provide clinicians with reliable prediction and disease assessment of heart failure.

Abstract Assessment of the posterior lateral knee pain poses diagnostic challenges, requiring accurate evaluation of various structures in light of the medical history and physical examination. Despite substantial progress in the ultrasonographic diagnosis of musculoskeletal disorders, the current protocol (EURO-MUSCULUS/USPRM. Basic scanning protocols for knee) fails to conduct a comprehensive investigation into the intricate, tendons, and ligaments of the posterior lateral knee. This pictorial review aims to bridge this gap by offering a systematic approach to utilize ultrasound examination of the less-discussed structures in this specific region. Providing cadaveric and magnetic resonance images, this essay demonstrates the efficacy of ultrasound in diagnosing posterior lateral knee pain. Notably, pathologies such as ligamentous sprains and tears are clearly discernible. Moreover, the integration of ultrasound guidance plays a vital role in reducing the risk of inadvertent neurovascular injury during injection, such as the common peroneal nerve and lateral genicular artery. This comprehensive approach will enhance clinicians’ understanding and equip them with effective management strategies for posterior lateral knee pain. Critical relevance statement In this visual exposition, we delve into the intricacies of the posterior lateral corner of the knee. Offering a methodical approach to employ ultrasound for visualization of the less-explored structures within this region, the authors aim to enhance the diagnosis in posterior lateral knee pain. Key points 1. Ultrasound excels at revealing intricate structures in the posterior lateral knee. 2. Due to proximity of vital structures, extreme caution is crucial during injections. 3. Employing dynamic scan and understanding ligaments enables a comprehensive exploration of pathologies. Graphical Abstract

Abstract Replication fork reversal, a critical protective mechanism against replication stress in higher eukaryotic cells, is orchestrated via a series of coordinated enzymatic reactions. The Bloom syndrome gene product, BLM, a member of the highly conserved RecQ helicase family, is implicated in this process, yet its precise regulation and role remain poorly understood. In this study, we demonstrate that the GCFC domain-containing protein TFIP11 forms a complex with the BLM helicase. TFIP11 exhibits a preference for binding to DNA substrates that mimic the structure generated at stalled replication forks. Loss of either TFIP11 or BLM leads to the accumulation of the other protein at stalled forks. This abnormal accumulation, in turn, impairs RAD51-mediated fork reversal and slowing, sensitizes cells to replication stress-inducing agents, and enhances chromosomal instability. These findings reveal a previously unidentified regulatory mechanism that modulates the activities of BLM and RAD51 at stalled forks, thereby impacting genome integrity.

Abstract Background Programmed cell death protein 1 (PD-1) is an immune checkpoint receptor expressed on the surface of T cells. High expression of PD-1 leads to T-cell dysfunction in the tumor microenvironment (TME). However, the mechanism of intracellular trafficking and plasma membrane presentation of PD-1 remains unclear. Methods Multiple databases of lung cancer patients were integratively analyzed to screen Rab proteins and potential immune-related signaling pathways. Imaging and various biochemical assays were performed in Jurkat T cells, splenocytes, and human peripheral blood mononuclear cells (PBMCs). Rab37 knockout mice and specimens of lung cancer patients were used to validate the concept. Results Here, we identify novel mechanisms of intracellular trafficking and plasma membrane presentation of PD-1 mediated by Rab37 small GTPase to sustain T cell exhaustion, thereby leading to poor patient outcome. PD-1 colocalized with Rab37-specific vesicles of T cells in a GTP-dependent manner whereby Rab37 mediated dynamic trafficking and membrane presentation of PD-1. However, glycosylation mutant PD-1 delayed cargo recruitment to the Rab37 vesicles, thus stalling membrane presentation. Notably, T cell proliferation and activity were upregulated in tumor-infiltrating T cells from the tumor-bearing Rab37 knockout mice compared to those from wild type. Clinically, the multiplex immunofluorescence-immunohistochemical assay indicated that patients with high Rab37+/PD-1+/TIM3+/CD8+ tumor infiltrating T cell profile correlated with advanced tumor stages and poor overall survival. Moreover, human PBMCs from patients demonstrated high expression of Rab37, which positively correlated with elevated levels of PD-1+ and TIM3+ in CD8+ T cells exhibiting reduced tumoricidal activity. Conclusions Our results provide the first evidence that Rab37 small GTPase mediates trafficking and membrane presentation of PD-1 to sustain T cell exhaustion, and the tumor promoting function of Rab37/PD-1 axis in T cells of TME in lung cancer. The expression profile of Rab37high/PD-1high/TIM3high in tumor-infiltrating CD8+ T cells is a biomarker for poor prognosis in lung cancer patients.

The goal of neural architecture search (NAS) is to either downsize the neural architecture and model of a deep neural network (DNN), adjust a neural architecture to improve its end result, or even speed up the whole training process. Such improvements make it possible to generate or install the model of a DNN on a small device, such as a device of internet of things or wireless sensor network. Because most NAS algorithms are time-consuming, finding out a way to reduce their computation costs has now become a critical research issue. The training-free method (also called the zero-shot learning) provides an alternative way to estimate how good a neural architecture is more efficiently during the process of NAS by using a lightweight score function instead of a general training process to avoid incurring heavy costs. This paper starts with a brief discussion of DNN and NAS, followed by a brief review of both model-dependent and model-independent training-free score functions. A brief introduction to the search algorithms and benchmarks that were widely used in a training-free NAS will also be given in this paper. The changes, potential, open issues, and future trends of this research topic are then addressed in the end of this paper.

Abstract Estrogen deficiency is one of the main causes of postmenopausal osteoporosis in elderly women. Hormone replacement therapy has been employed to manage postmenopausal osteoporosis; however, it has raised concerns related to heart attacks and breast cancer. Sesame oil has been reported to affect sex hormone status. The aim of the present study is to evaluate the effect of sesame oil supplement on postmenopausal osteoporosis in rats. We used female Sprague Dawley rats that underwent bilaterally ovariectomy (OVX) as an experimental postmenopausal osteoporosis animal model. These rats were orally administrated sesame oil (0.25 or 0.5 mL/kg/day) for four months as the therapeutic group. We assessed bone mineral density (BMD) and the levels of osteocalcin, procollagen-I C-terminal propeptide (PICP), collagen cross-linked N-telopeptide (NTx), estradiol, and aromatase in the sera. The daily supplementation of sesame oil significantly increased BMD, serum osteocalcin levels, and trabecular areas in the OVX-treated rats. Sesame oil also elevated serum PICP levels and decreased NTx levels in these rats. Furthermore, sesame oil effectively maintained serum estradiol and aromatase levels in the OVX-induced osteoporosis rats. In conclusion, daily supplementation of sesame oil prevents postmenopausal osteoporosis by maintaining serum estrogen and aromatase levels, while also modulating the imbalance between bone formation and resorption in osteoporosis rats.

A cooperative intelligent transport system (C-ITS) enables information sharing among ITS subsystems, such as vehicle and roadside infrastructure, with vehicle-to-everything (V2X) communications. Novel C-ITS applications aim to reduce traffic congestion and improve road safety. For example, a roadside unit (RSU) can sense the traffic status of an intersection and share the information to nearby vehicles to prevent potential collision, i.e., the intersection movement assist (IMA) scenario. Typically, C-ITS applications are developed in a simulated world to mitigate the high costs and safety hazards associated with the real-world counterpart. Unfortunately, existing simulation tools focus primarily on modeling vehicle-to-vehicle (V2V) communications, rather than the vehicle-to-infrastructure (V2I) communications involved in the above example. This poses a great challenge for developing V2I-based applications, especially for the application-level performance assessment on such systems. This work proposes a software framework that enables the simulation of full software stacks for the ITS subsystems, i.e., vehicle and RSU. This full-stack simulation capability enables hardware-in-the-loop simulations, evaluating the application-level performance and relative cost in the early stage of system development. This can shorten the time to market for C-ITS applications. We believe that this framework paves the way toward the development of novel V2I applications.

Thousands of long-distance mobile mRNAs were identified from different grafting systems, based on high-throughput sequencing technology. Moreover, the long-distance delivery of RNAs was proved to involve multiple mechanisms. Here, we analyzed the homology, motif, and tRNA-like structure (TLS) of long-distance mobile mRNAs identified by RNA-seq as well as the RNA-binding protein (RBP) in nine grafting combinations including Arabidopsis thaliana, Vitis vinifera, Cucumis sativus, Citrullus lanatus, Nicotiana benthamiana, Malus domestica, Pyrus spp., Glycine max and Phaseolus vulgaris. Although several mRNAs were found to be shared in herbaceous, woody, and related species, the vast majority of long-distance mobile mRNAs were species-specific. Four non-specific movement-related motifs were identified, while the TLS was not necessary for mRNA long distance mobility. In addition, we found that RBPs were conserved among herbaceous and woody plants as well as related species. This paper reports a further in-depth analysis of the endogenous mechanisms by which the species-specific transportable mRNAs were selected by bioinformatics, in order to provide insights for future research on long-distance mobile mRNAs.

Abstract Hypoxic-ischemic brain damage (HIBD) is a leading cause of neonatal death and neurological dysfunction. Neuroinflammation is identified as one of the crucial pathological mechanisms after HIBD, and natural killer group 2 member D (NKG2D) is reported to be implicated in the pathogenesis of immunoinflammatory diseases. However, the role of NKG2D in neonatal HIBD is seldomly investigated. In this study, a neonatal mice model of HIBD was induced, and the role of the NKG2D in neuroinflammation and brain injury was explored by intracerebroventricular injection of lentivirus to knockdown NKG2D in neonatal mice with HIBD. The results showed that a significant increase in NKG2D protein level in the brain of neonatal mice with HIBD. The NKG2D knockdown in the brain significantly alleviated cerebral infarction, neurobehavioral deficits, and neuronal loss in neuronal HIBD. Moreover, the neuroprotective effect of NKG2D knockdown was associated with inhibition of the activation of microglia and astrocytes, expression of NKG2D ligands (NKG2DLs) and DAP10, and the nuclear translocation of NF-κB p65. Our findings reveal NKG2D knockdown may exert anti-inflammatory and neuroprotective effects in the neonatal mice with HIBD through downregulation of NKG2D/NKG2DLs/DAP10/NF-κB pathway. These results suggest that NKG2D may be a potential target for the treatment of neonatal HIBD.

Abstract Background Tumor immunotherapy is a new treatment breakthrough for retroperitoneal liposarcoma (RPLS), which is highly invasive and has few effective treatment options other than tumor resection. However, the heterogeneity of the tumor immune microenvironment (TIME) leads to missed clinical diagnosis and inappropriate treatment. Therefore, it is crucial to evaluate whether the TIME of a certain part of the tumor reliably represents the whole tumor, particularly for very large tumors, such as RPLS. Methods We conducted a prospective study to evaluate the TIME in different regions of dedifferentiated RPLS (DDRPLS) by detecting the expressions of markers such as CD4+, CD8+, Foxp3+, CD20+, CD68+, LAMP3+, PD-1+ tumor-infiltrating lymphocytes (TILs), and PD-L1 in tumors and corresponding paratumor tissues via immunohistochemistry and RNA sequencing. Results In DDRPLS, very few TILs were observed. Differentially expressed genes were significantly enriched in cell part and cell functions, as well as the metabolic pathway and PI3K-Akt signaling pathway. In addition, for most tumors (70–80%), the TIME was similar in different tumor regions. Conclusions For most tumors (70–80%), the TIME in any region of the tumor reliably represents the whole tumor. DDRPLS may regulate cell functions by modulating the metabolic and PI3K-Akt signaling pathways to promote its malignant behavior.

Abstract First-line chemoimmunotherapy (with or without bevacizumab) has improved outcomes in advanced non-small cell lung cancer (NSCLC). Here, this open-label, multi-cohort phase II study (NCT05329025) was done to investigate the safety and efficacy of QL1706 (a single bifunctional MabPair product against PD-1 and CTLA-4) and chemotherapy with or without bevacizumab in this population. Patients were enrolled into five different cohorts based on genotype (cohorts 1-4, epidermal growth factor receptor [EGFR] wild-type; cohort 5, EGFR-mutant and progressed on EGFR-tyrosine kinase inhibitors [TKIs]). Between June 11, 2021 and December 29, 2021, 91 patients were enrolled. Most frequent treatment-related adverse events (TRAEs) included decreased appetite (60 [65.9%]), anemia (60 [65.9%]), infusion-related reactions (48 [52.7%]), and pruritus (44 [48.4%]). Grade ≥ 3 TRAEs occurred in 30 (33.0%) patients. Twenty-seven (45%) patients with wild-type EGFR achieved partial response (PR) (objective response rate [ORR] = 45%) and had a median progression-free survival (mPFS) of 6.8 months (95% CI: 5.2-9.7). For 31 patients harboring mutated EGFR, 17 (54.8%) achieved PR (ORR = 54.8%), with an mPFS of 8.5 months (95% CI: 5.72-not evaluable). Overall, QL1706 plus chemotherapy, regardless of having bevacizumab, was generally tolerable and had promising antitumor activity for EGFR wild-type advanced NSCLC in first-line setting. Moreover, QL1706 plus chemotherapy and bevacizumab showed favorable antitumor activity for patients who had EGFR mutated NSCLC but failed in TKI therapy, demonstrating a potential for treating this population.

Background: The rate of preterm birth is increasing globally. It causes significant short-term and long-term health care burdens. A comprehensive recognition of the risk factors related to preterm births is important in the prevention of preterm birth. Our study is to investigate the incidence and maternal risk factors of preterm birth from a nationwide population-based perspective. Methods: This is a retrospective cohort study. All live births from 2004 to 2014 in Taiwan enrolled. The main data source was Taiwan’s Birth Certificate Application (BCA) database. The BCA database was linked with the National Health Insurance Research Database (NHIRD) to establish any links between information on newborns and maternal underlying disease. Results: A total of 1,385,979 births were included in the analysis. The incidence of preterm birth increased gradually in Taiwan from 8.85% in 2004 to 10.73% in 2014. Maternal age, socioeconomic status, maternal allergy and autoimmune diseases, gynecological diseases, and pregnancy-related complications were significant risk factors for preterm birth. Conclusion: The overall incidence of preterm births has gradually increased in Taiwan. Maternal age, socioeconomic status, certain underlying diseases, and pregnancy-related complications were risk factors for preterm birth.

Background: The role of environmental contamination in COVID-19 transmission within hospitals is still of interest due to the significant impact of outbreaks globally. However, there is a scarcity of data regarding the utilization of environmental sampling for informing infection control measures during SARS-CoV-2 outbreaks. Methods: This retrospective study analyzed incident event investigations conducted at a single center from May 1, 2021, to August 31, 2021. Investigations were initiated following the identification of a COVID-19 confirmed case (referred to as the index case) who had stayed in a hospital area outside the dedicated COVID-19 ward/bed and without specific COVID-19 precautions. Measures to prevent intra-hospital spread included contact tracing, adjusted testing policies, isolation of confirmed cases, quarantine of close contacts, environmental disinfection, and PCR testing of environmental samples. Results: Among the 18 incident events investigated, the index case was a healthcare personnel in 8 events, a patient in 8 events, and a caregiver in 2 events. The median number of confirmed COVID-19 cases within 14 days was 13 (IQR, 7–31) for events with SARS-CoV-2 RNA detected on environmental surfaces, compared to only one (IQR, 1–1.5) for events without surface contamination (P = 0.04). Environmental contamination was independently associated with a higher number of COVID-19 cases (P

Abstract Background The gut microbiota plays a crucial role in coronary artery disease (CAD) development, but limited attention has been given to the role of the microbiota in preventing this disease. This study aimed to identify key biomarkers using metagenomics and untargeted metabolomics and verify their associations with atherosclerosis. Methods A total of 371 participants, including individuals with various CAD types and CAD-free controls, were enrolled. Subsequently, significant markers were identified in the stool samples through gut metagenomic sequencing and untargeted metabolomics. In vivo and in vitro experiments were performed to investigate the mechanisms underlying the association between these markers and atherosclerosis. Results Faecal omics sequencing revealed that individuals with a substantial presence of Faecalibacterium prausnitzii had the lowest incidence of CAD across diverse CAD groups and control subjects. A random forest model confirmed the significant relationship between F. prausnitzii and CAD incidence. Notably, F. prausnitzii emerged as a robust, independent CAD predictor. Furthermore, our findings indicated the potential of the gut microbiota and gut metabolites to predict CAD occurrence and progression, potentially impacting amino acid and vitamin metabolism. F. prausnitzii mitigated inflammation and exhibited an antiatherosclerotic effect on ApoE−/− mice after gavage. This effect was attributed to reduced intestinal LPS synthesis and reinforced mechanical and mucosal barriers, leading to decreased plasma LPS levels and an antiatherosclerotic outcome. Conclusions Sequencing of the samples revealed a previously unknown link between specific gut microbiota and atherosclerosis. Treatment with F. prausnitzii may help prevent CAD by inhibiting atherosclerosis.

PURPOSE: The present study aims to assess the short-term clinical outcomes and safety of transarterial embolization (TAE) for symptomatic hand osteoarthritis (OA) refractory to conservative treatment. METHODS: The present retrospective cohort pilot study included nine patients who underwent TAE for symptomatic OA-associated hand pain in a single tertiary center between November 2022 and January 2023. The baseline and post-procedural OA-associated hand pain and function were assessed using the visual analog scale (VAS) and the Australian Canadian Hand Osteoarthritis Index (AUSCAN). The use of conservative treatment and pain medications was also recorded. Post-procedural adverse events were evaluated according to the Society of Interventional Radiology classification. RESULTS: Compared with the baseline, the overall VAS scores were significantly decreased at 1-week, 1-month, 3-months, and 6-months after TAE (76 ± 15 mm versus 34 ± 18 mm, P < 0.001; 32 ± 11 mm, P < 0.001; 21 ± 15 mm, P < 0.001; 18 ± 19 mm, P = 0.002). Similarly, improvement in the mean total AUSCAN scores (22.0 ± 10.0 versus 13.2 ± 6.6, P = 0.007; 14.11 ± 7.3, P = 0.004; 9.8 ± 6.8, P = 0.004; 9.3 ± 7.4, P = 0.011) were documented. The use of other conservative treatment methods also gradually decreased. There were no severe adverse events reported during the follow-up period. CONCLUSION: TAE is a feasible and safe treatment method for symptomatic hand OA refractory to conservative treatment. This minimally invasive procedure effectively relieves debilitating OA-associated joint pain and restores hand function with a durable treatment effect.

Road information plays an increasingly important role in applications, such as map updating, urban planning, and intelligent supervision. However, roads in remote sensing images may be shaded by trees and buildings or interfered with by farmland. These intrinsic image features can cause road extraction results to suffer from breakage and misidentification problems. To address these problems, this article improves on D-LinkNet and proposes a dual codec structure network, namely RUW-Net. Specifically, we use ReSidual U-blocks instead of ordinary residual blocks to extract more global contextual information during the encoding stage. Moreover, we propose a decoder-encoder combination (DEC) module to build a dual codec structure. The DEC module links the decoder of the first U-block and the encoder of the following U-block to narrow the semantic gap in the encoding and decoding process. The RUW-Net model can extract more multiscale contextual features and effectively use them to enhance the semantic information of road entities. Therefore, the RUW-Net model can obtain more accurate extraction results. We conducted a series of experiments on public datasets, such as DeepGlobe, including comparative, robustness, and ablation experiments. The results show that the proposed model alleviates the road extraction breakage and misidentification problems. Compared with other representative methods, the RUW-Net performs better in terms of completeness and accuracy of road extraction results; overall, its extraction results are also the best. The RUW-Net model provides a new idea for road extraction from remote sensing images.

Lubrication and heat transfer control are two significant functions of mold fluxes. In order to coordinate the contradiction between lubrication and heat transfer, the effects of BaO and Li2O on basic characteristics of CaO-SiO2 based mold fluxes were studied by hemispherical melting temperature instrument, rotating cylinder method, X-ray diffractometer (XRD) in present study. The results show that the melting temperature and viscosity at 1300°C all represent a downward trend with BaO and Li2O enhancement at different basicity, and the break temperature decrease with BaO addition while decrease and then increase with Li2O addition, which illustrates that Li2O content should be no more than 0.8 wt% for the purpose of lubrication. Meanwhile, to ensure a sufficient thickness of the liquid slag film and avoid discontinuity of the liquid slag film, the BaO content is better to be 10 wt% with low melting temperature and viscosity. The main crystalline phase in the mold fluxes is cuspidine (3CaO·2SiO2·CaF2), and the crystallization ratio rises sharply when basicity increased to 1.65. For better deal with the contradiction of lubrication and heat transfer, the mold fluxes composition w(BaO) = 10 wt%, w(Li2O) = 0.8 wt%, R ≥1.65 is reasonable, which has a profound impact on high crystallization and lubricity mold fluxes.

Abstract Aims In-depth studies on plant ion uptake and plant growth-promoting rhizobacteria (PGPR) at the molecular level will help to further reveal the effects of PGPR on plants and their interaction mechanisms under salt stress. Methods Cotton was inoculated with a PGPR-Enterobacter cloacae Rs-35, and the ion uptake capacity, membrane transporter protein activity, and expression of key genes were determined under salt stress. Changes in the endogenous hormone content of cotton were also determined. Further, the genome-wide metabolic pathway annotation of E. cloacae Rs-35 and its differential enrichment pathway analysis of multi-omics under salinity environments were performed. Results In a pot experiment of saline-alkali soil, E. cloacae Rs-35-treated cotton significantly increased its uptake of K+ and Ca2+ and decreased uptake of Na+, elevated the activity of the H+-ATPase, and increased the sensitivity of the Na+/H+ reverse transporter protein on the vesicle membrane. Meanwhile, inoculation with E. cloacae Rs-35 could promote cotton to maintain the indole-3-acetic acid (IAA) content under salt stress. Genome-wide annotation showed that E. cloacae Rs-35 was respectively annotated to 31, 38, and 130 related genes in osmotic stress, phytohormone and organic acid metabolism, and ion uptake metabolic pathway. Multi-omics differences analysis showed that E. cloacae Rs-35 were enriched to tryptophan metabolism, multiple amino acid biosynthesis, carbon and glucose synthesis, and oxidative phosphorylation metabolic pathways at the transcriptome, proteome, and metabolome. Conclusion E. cloacae Rs-35 can promote cotton balance cell ion concentration, stabilize intracellular IAA changes, stimulate induction of systemic tolerance, and promote the growth of cotton plants under salt stress.

Abstract Background Significant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization–frozen embryo transfer (IVF-FET) among polycystic ovary syndrome (PCOS) patients have been previously reported by our group. We aimed to assess whether transvaginal Lactobacillus supplementation can reverse LGT dysbiosis and further improve perinatal outcomes in PCOS patients after IVF-FET. Methods/design This is a protocol for a multicenter, open-label, randomized controlled trial in China. Women diagnosed with PCOS who are undergoing IVF-FET treatment will be recruited. Allocation to the intervention/control arms at a ratio of 1:1 will be executed by an electronic randomization system. Participants in the intervention arm will receive the live Lactobacillus capsule vaginally for 10 consecutive days before embryo transfer, while those in the control arm will receive standard individualized care. The primary outcomes will be the clinical pregnancy rate, implantation rate, and live birth rate. 16S rRNA sequencing and liquid chromatography–mass spectrometry will be conducted to evaluate the LGT microbiome and systemic metabonomics before and after the intervention. A sample of 260 participants will provide 95% power to detect a 20% increase in the rate of clinical pregnancy (α = 0.025, one-tailed test, 15% dropout rate). A total of 300 participants will be recruited. Discussion This is the first large and multicenter randomized controlled trial aimed at assessing the efficacy of transvaginal Lactobacillus supplementation on restoring the LGT microbiome and improving perinatal outcomes in PCOS patients after IVF-FET. This pragmatic trial is promising for increasing the rates of clinical pregnancy and live birth in PCOS patients after IVF-FET. Ethics and dissemination Ethical review approval was obtained from the Medical Research Ethics Committees of the International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University (15 October 2020, GKLW 2020-29). To maximize dissemination, these findings will be reported in open access publications in journals with high impact, and oral and poster conference presentations will be performed. Trial registration ChiCTR ChiCTR2000036460. Registered on 13 September 2020, https://www.chictr.org.cn/showproj.html?proj=59549 .

Background: The immunoglobulin E (IgE) response to Angiostrongylus cantonensis infection increases in the host. This study analyzed the IgG and IgE responses detected in different body fluids of A. cantonensis-infected mice. Methods: BALB/c (high susceptibility), CBA (medium), and C57BL/6 and C57BL/10 (resistance) strain mice were used in this study. The levels of IgM, IgG, and IgE in the serum and cerebrospinal fluid (CSF) from infected mice were compared. A. cantonensis-reactive antigens from BALB/c and C57BL/6 mice CSF were also analyzed. Results: Antibodies against fifth-stage larvae (L5) antigens increased in mice CSF, particularly IgE, relate to worm rejection and the susceptibility of different mouse strains. The increased IgE level in BALB/c mice CSF is lower than that from others, suggesting IgE response in brain is more important than that in serum. Anti-L5 and anti-excretory/secretory (ES) antigen IgE and IgG responses in CSF were analyzed. In addition, the antibody-dependent eosinophil-mediated cytotoxicity induced by anti-excretory/secretory (ES) antigen antibodies may be the reason of severe brain inflammation in infected BALB/c mice. IgE and IgG antibodies against a 105 kDa protein of L5 antigen was detected at week 3 post-infection in C57BL/6 mice and week 5 post-infection in BALB/c mice. We suggest that 105 kDa protein is related with the antibody response of A. cantonensis-infected mice. Conclusion: We found that IgE antibodies in mice CSF against L5 antigens related to worm rejection in mice brains. This study may help to identify specific angiostrongyliasis markers that can be applied for clinical diagnosis and treatment in future.

Autophagy leads to cellular tolerance of the therapeutic pressure of chemotherapeutic drugs, resulting in treatment resistance. Therefore, the effective monitoring of the autophagy status of tumors in vivo and the regulating of the autophagy level are crucial for improving the efficacy of chemotherapy. In this work, we grafted nitroxide radicals onto the surface of iron oxide nanoparticles (Fe3O4 NPs) using dendrimer polymers, yielding Fe3O4-NO· NPs that are responsive to reactive oxygen species (ROS) and possess enhanced T1 and T2 signal capabilities in a magnetic resonance imaging (MRI) measurement. The ROS in tumor cells generated by autophagy quenches the nitroxide radicals, thereby weakening the T1 signal. In contrast, Fe3O4 NPs are unaffected by intracellular ROS, leading to a stable T2 signal. By comparing the intensity ratio of T1 to T2 in Fe3O4-NO· NPs, we can evaluate the in vivo autophagy status within tumors in real time. It also revealed that Fe3O4-NO· NPs loaded with doxorubicin (Dox) and combining the autophagy inhibitor exhibited high antitumor activity in cells and tumor-bearing mice. This system, which combines real-time monitoring of tumor cell autophagy with the delivery of chemotherapeutic drugs, provides an innovative and effective strategy for tumor treatment with potential clinical application prospects.

We have studied the parameters of preliminary breakdown (PB) pulses in 395 normal and 319 inverted intracloud (IC) flashes observed in Gifu, Japan, and Ningxia, China, respectively, by using a low-frequency mapping system called fast antenna lightning mapping array (FALMA). These parameters are extracted from the first half of the PB pulses. It is found that compared to normal IC flashes, inverted IC flashes exhibited PB pulses with slower rise times (6.8 vs. 3.1 μs), wider half-peak widths (3.8 vs. 2.5 μs), longer zero-crossing times (26.2 vs. 14 μs), and extended fall times (4 vs. 3.2 μs). We further demonstrated that such discrepancies between normal and inverted IC flashes should not be caused by subjective factors, like noise threshold setting, or objective factors, like signal propagation distance. Based on this analysis, finally, we inferred that the discrepancies should be a reflection of the PB channel properties of normal and inverted IC flashes.

Major global public health emergencies face unprecedented challenges, such as an infodemic and scientific disputes, and governments especially need to implement fast and effective crisis communication. Firstly, this paper takes the Elaboration Likelihood Model as a framework and constructs a crisis communication persuasion effect evaluation method with emotion analysis. Secondly, this paper takes the crisis communication at the beginning of the COVID-19 outbreak in China as an example and examines the persuasive effects of the peripheral route, represented by medical experts, and the central route, represented by mainstream media. This study finds that the peripheral route of persuasive communication can quickly establish communication trust and quickly change the public’s peripheral attitude, but the persuasive effect is unstable. The central route of persuasive communication demonstrates a significantly positive, stable, and anti-interference persuasive effect. Dual-subject persuasion is an important strategy for controlling an outbreak by rapidly establishing communication trust, combating an infodemic, boosting public confidence, and popularizing medical knowledge. This study evaluates the persuasive effects of crisis communication in the early stages of the COVID-19 outbreak in China, hoping to provide valuable practical references for crisis communication during the outbreak in future global public health emergencies.

A 27-year-old female presented with persistent right medial plantar pain that developed over six months following an ankle sprain. The pain, described as sharp and radiating to the toes, progressively worsened, affecting her ability to walk. An initial ultrasound examination suggested medial plantar nerve compression by a lipoma, prompting her referral for ultrasound-guided hydrodissection. During the pre-procedure assessment, sono-palpation (palpation using the ultrasound transducer) localized the pain to the Master Knot of Henry—where the medial plantar nerve, artery, and flexor tendons intersect. No lipoma but a normal fat pad was observed. Ultrasound-guided hydrodissection with 5% dextrose mixed with lidocaine and saline was performed. After two sessions, her pain significantly decreased, with her visual analogue scale score dropping from 8 to 5 after the first session and to 2 after the second, allowing her to resume normal activities. This case highlights the value of ultrasound in accurately diagnosing and treating conditions involving the Master Knot of Henry.

In recent years, navigating rotor drones in complex and dynamic environments has been a significant challenge. This paper proposes an improved path planning method by integrating the enhanced Informed-RRT* algorithm with the Dynamic Window Approach (DWA) algorithm. Firstly, the probability weight function for sampling direction is dynamically adjusted based on the Euclidean distance between the start and goal points to obtain higher-quality sampling points. Secondly, the Artificial Potential Field (APF) concept is introduced during the generation of new nodes, applying the improved APF method to the elliptical sampling area to guide the direction of new node generation. This significantly reduces the number of redundant nodes, enhances the convergence speed, and improves the obstacle avoidance efficiency. Then, a polynomial fitting method is employed to optimize the path, yielding a smoother trajectory. Finally, the improved DWA algorithm is integrated. Initially, the Informed-RRT* algorithm generates an optimal path from the starting point to the goal point in the global space, which is then provided as an initial reference path to the DWA algorithm. During actual operation, the DWA algorithm dynamically adjusts control inputs based on the current position, speed, and reference path of the drone, ensuring that the drone can avoid dynamic obstacles and unknown static obstacles in real time while staying as close to the reference path as possible.

Wave erosion of slopes can easily trigger landslides into marine environments and pose severe threats to both the ecological environment and human activities. Therefore, near-shore slope monitoring becomes crucial for preventing and alerting people to these potential disasters. To achieve a comprehensive understanding, it is imperative to conduct a detailed investigation into the dynamics of wave erosion processes acting on slopes. This research is conducted through flume tests, using a wave maker to create waves of various heights and frequencies to erode the slope models. During the tests, seismic signals, acoustic signals, and pore pressure generated by wave erosion and slope failure are recorded. Seismic and acoustic signals are analyzed, and time-frequency spectra are calculated using the Hilbert–Huang Transform to identify the erosion events and signal frequency ranges. Arias Intensity is used to assess seismic energy and explore the relationship between the amount of erosion and energy. The results show that wave height has a more decisive influence on erosion behavior and retreat than wave frequency. Rapid drawdown may potentially cause the slope to slide during cyclic swash and backwash wave action. As wave erosion changes from swash to impact, there is a significant increase in the spectral magnitude and Power Spectral Density (PSD) of both seismic and acoustic signals. An increase in pore pressure is observed due to the rise in the run-up height of waves. The amplitude of pore pressure will increase as the slope undergoes further erosion. Understanding the results of this study can aid in predicting erosion and in planning effective management strategies for slopes subject to wave action.

Tillage practices significantly influence crop yield and soil quality. This study investigated the impact of rotary tillage (RT) and deep tillage (DT) on soil properties, microbial diversity, and melon (Cucumis melo L.) root growth and yield. RT involved breaking up the topsoil to a depth of 15 cm using a rotary tiller, while DT employed a rotary tiller followed by a moldboard plow to turn the soil layer over to a depth of 35 cm. The melon variety “Nasimi” was used as the material. Our findings revealed a remarkable response of soil phosphorus to tillage practices. High-throughput sequencing results revealed a significant impact of tillage practices on the soil fungal composition, richness, and diversity but little impact on the bacterial communities. Compared to RT, DT markedly enhanced melon root length, root surface area, root volume, and mean root diameter by 47.42%, 56.70%, 58.83%, and 27.28%, respectively. Additionally, DT treatments significantly increased melon yield (53.46%) compared to RT. The results indicate that DT improves soil nutrient availability, affects soil fungal community characteristics, and optimizes root distribution in soil, thereby improving melon yield. The findings offer valuable theoretical insights for the implementation of effective tillage practices in open-field melon cultivation.

ObjectivesFibromyalgia (FM) has been associated with decreased hippocampal volume; however, the atrophy patterns of hippocampal subregions have not yet been identified. We therefore aimed to evaluate the volumes of hippocampal subregions in FM patients with mild cognitive impairment (MCI), and to explore the relationship between different subregional alterations and cognitive function.MethodsThe study included 35 FM patients (21 with MCI and 14 without MCI) and 35 healthy subjects. All subjects performed the Montreal Cognitive Assessment (MoCA) to assess cognitive function. FreeSurfer V.7.3.2 was used to calculate hippocampal subregion volumes. We then compared hippocampal subregion volumes between the groups, and analyzed the relationship between hippocampal subregion volume and cognitive function using a partial correlation analysis method.ResultsCompared with the healthy subjects, FM patients with MCI had smaller hippocampal volumes in the left and right CA1 head, Molecular layer head, GC-DG head, and CA4 head, and in the left Presubiculum head. Poorer executive function, naming ability, and attention were associated with left CA1 head and left Molecular layer head atrophy. By contrast, hippocampal subregion volumes in the FM patients without MCI were slightly larger than or similar to those in the healthy subjects, and were not significantly correlated with cognitive function.ConclusionSmaller volumes of left CA1 head and left Molecular layer head were associated with poorer executive function, naming ability, and attention in FM patients with MCI. However, these results were not observed in the FM patients without MCI. These findings suggest that the hippocampal subregions of FM patients might present compensatory mechanisms before cognitive decline occurs.

ObjectivesJunctional proteins are involved in tumorigenesis. Therefore, this study aimed to investigate the association between junctional genes and the prognosis of patients with lung adenocarcinoma (LUAD).MethodsTranscriptome, mutation, and clinical data were retrieved from The Cancer Genome Atlas (TCGA). “Limma” was used to screen differentially expressed genes. Moreover, Kaplan–Meier survival analysis was used to identify junctional genes associated with LUAD prognosis. The junctional gene-related risk score (JGRS) was generated based on multivariate Cox regression analysis. An overall survival (OS) prediction model combining the JGRS and clinicopathological properties was proposed using a nomogram and further validated in the Gene Expression Omnibus (GEO) LUAD cohort.ResultsTo our knowledge, this study is the first to demonstrate the correlation between the mRNA levels of 14 junctional genes (CDH15, CDH17, CDH24, CLDN6, CLDN12, CLDN18, CTNND2, DSG2, ITGA2, ITGA8, ITGA11, ITGAL, ITGB4, and PKP3) and clinical outcomes of patients with LUAD. The JGRS was generated based on these 14 genes, and a higher JGRS was associated with older age, higher stage levels, and lower immune scores. Thus, a prognostic prediction nomogram was proposed based on the JGRS. Internal and external validation showed the good performance of the prediction model. Mechanistically, JGRS was associated with cell proliferation and immune regulatory pathways. Mutational analysis revealed that more somatic mutations occurred in the high-JGRS group than in the low-JGRS group.ConclusionThe association between junctional genes and OS in patients with LUAD demonstrated by our “TCGA filtrating and GEO validating” model revealed a new function of junctional genes.

Problem-solving skills are an ability that must be cultivated to equip students with the skills needed to deal with today’s increasingly complex and volatile environment. Computational thinking represents a new paradigm in problem-solving skills. After Wing proposed Computational Thinking as problem-solving skills in 2006, other scholars investigated this topic; nevertheless, the link between Computational Thinking and problem-solving has not been clearly discussed in previous studies. To uncover evidence for the connection between Computational Thinking and problem-solving skills, we conduct a systematic literature review of 37 papers collected from Web of Science database. The results indicate that (a) problem-solving is discussed in the 37 articles in the context of Computational Thinking, (b) the most frequently employed Computational Thinking stages in problem-solving skills are decomposition, pattern recognition, abstraction, and algorithm, (c) Computational Thinking is closely linked to problem-solving, and (d) Computational Thinking and problem-solving stages serve the same functions in solving problems. The results of this study will encourage the development of education research, particularly in the application of CT as a problem-solving tool in various real-life scenarios.

C1q domain-containing (C1qDC) proteins are significant pattern recognition receptors in the innate immune system that play important roles in regulating immune responses in vertebrates and invertebrates. In this study, a gene encoding the fish C1qDC (designated CiC1ql2) from the grass carp Ctenopharyngodon idella was characterized for the first time. Like other reported C1ql proteins, CiC1ql2 contains a conserved C1q domain and a signal peptide at its 5′ end. Expression profile analysis revealed that CiC1ql2 was mostly expressed in the intestine but was expressed at low levels in the brain and gill. In vivo injection experiments directly revealed that CiC1ql2 exhibited strong responsiveness to Aeromonas hydrophila, Aeromonas veronii and pathogen-associated molecular pattern (PAMP) challenge, as indicated by the presence of lipopolysaccharide (LPS) and peptidoglycan (PGN), and that the expression of these genes was significantly upregulated in the intestine of C. idella. Additionally, the recombinant CiC1ql2 protein obviously promoted the agglutination of the gram-negative bacteria A. hydrophila and A. veronii and the gram-positive bacterium Bacillus subtilis, as shown by in vitro binding experiments. Moreover, CiC1ql2 protein injection experiment revealed that CiC1ql2 significantly enhanced the expression levels of classic complement genes (C3, C5, and C7) and inflammatory cytokines (TNF-α, IL-1β, and IL-8), while knockdown of CiC1ql2 decreased the expression of these immune-related genes. Taken together, our results suggested that CiC1ql2 could act as a pathogenic pattern recognition receptor involved in complement activation and that this might be related to the intestinal defense of C. idella against bacterial infection.

Current intraoperative pressure monitoring methods still face significant limitations in perception and feedback, struggling to strike a balance between precision and wearable flexibility. Inspired by biological skin, we propose a biomimetic tactile sensing system for pressure monitoring during extracorporeal circulation, comprising flexible pressure sensors and artificial synaptic transistors. Aimed at addressing the aforementioned issues, our system employs a pyramid-shaped elastic design for flexible pressure sensors, utilizing biocompatible materials polydimethylsiloxane and multi-walled carbon nanotubes as the strain-sensitive layer. This configuration boasts ultra-high sensitivity and resolution (115 kPa−1), accurately detecting subtle pressure changes, such as blood circulation wall pressures. With artificial synaptic transistors as the information processing core, our system successfully simulates crucial neural processing functions, including excitatory post-synaptic currents and double-pulse facilitation, while providing alerts for abnormal blood pressure signals. This system facilitates real-time data processing at the device edge, reducing power consumption, improving efficiency, and better addressing the demands of large-scale physiological pressure data processing. It presents a significant reference for future developments in biomedical electronics and bionics.

Solid acid catalysts are widely used in the field of biomass catalytic conversion owing to their advantages of low environmental pollution, easy separation and reusability. Nevertheless, there are relatively few studies on the mechanism of solid acid liquefaction for biomass. In this study, the effect of acid strength and acid amount of various solid acids on the liquefaction efficiency has been investigated using waste bamboo sawdust generated from the pulp and paper industry as the raw material. In addition, the physicochemical changes of cellulose, hemicellulose and lignin during the reaction process of bamboo sawdust have been studied, and the liquefaction mechanism of bamboo sawdust under the action of various solid acids has been concluded. As a result, the liquefaction efficiency of bamboo sawdust under the polyol system of PEG400/propanetriol is mainly related to the acid strength of the solid acid, and the greater the acid strength of the solid acid, the better the catalytic effect on the bamboo sawdust, in which the residual amount of bamboo sawdust liquefaction catalyzed by the SPA catalyst is only 17.72%. Noteworthy, the most difficult component to liquefy is the crystallization of natural cellulose I into cellulose II during the reaction process, which is the primary obstacle to the complete liquefaction of bamboo sawdust by solid acid. Overall, these findings are valuable for the high value utilization of waste bamboo sawdust in the pulp and paper industry, as well as the application of solid acid catalytic technology for biomass.

Metabolic diseases are comprehensive disease based on obesity. Numerous cumulative studies have shown a certain correlation between the fluctuating abundance of Akkermansia muciniphila and the occurrence of metabolic diseases. A. muciniphila, a potential probiotic candidate colonized in the human intestinal mucus layer, and its derivatives have various physiological functions, including treating metabolic disorders and maintaining human health. This review systematically explicates the abundance change rules of A. muciniphila in metabolic diseases. It also details the high efficacy and specific molecules mechanism of A. muciniphila and its derivatives in treating obesity, type 2 diabetes mellitus, cardiovascular disease, and non-alcoholic fatty liver disease.

PurposeWe aimed to explore the effects of percutaneous coronary intervention (PCI) on the ophthalmic artery (OA) hemodynamics in patients with acute coronary syndrome (ACS).MethodsA total of 73 participants (Group0: healthy controls, Group1: Patients with ACS underwent PCI < 3 months, Group2: Patients with ACS underwent PCI ≥ 3 months) were enrolled. Computed tomographic angiography images were used to construct three-dimensional models of participants' OAs. Numerical simulations based on computational fluid dynamics were used to acquire hemodynamic parameters.ResultsThe angle between the OA and internal carotid artery in Group2 was significantly larger compared with Group0 and Group1 (P = 0.003 and P = 0.044). Hemodynamic simulation showed a significantly slower OA blood velocity in Group1 than in the control (P < 0.001) and Group2 (P = 0.033). Lower wall shear stress was found in Group1 than that in control (P = 0.040). Patients after PCI had a higher wall pressure than healthy controls (P = 0.012 and P = 0.004). Mass flow ratios were decreased in Group1 and Group2 (P = 0.021 and P = 0.002). The hemodynamic parameters of OA were correlated with several clinical indicators.ConclusionsThe OA blood flow velocity of patients with ACS after PCI initially slowed down, which increased the risk of plaque formation, and then showed an increasing trend. There was a correlation between OA hemodynamic parameters and clinical indexes related to cardiac stress. Ischemia-reperfusion injury and changes in blood flow status after PCI may affect OA morphology and hemodynamics, leading to ocular lesions.Trial registrationChiCTR2100050428.

Abstract Follicle-stimulating hormone (FSH) is involved in mammalian reproduction via binding to FSH receptor (FSHR). However, several studies have found that FSH and FSHR play important roles in extragonadal tissue. Here, we identified the expression of FSHR in human and mouse pancreatic islet β-cells. Blocking FSH signaling by Fshr knock-out led to impaired glucose tolerance owing to decreased insulin secretion, while high FSH levels caused insufficient insulin secretion as well. In vitro, we found that FSH orchestrated glucose-stimulated insulin secretion (GSIS) in a bell curve manner. Mechanistically, FSH primarily activates Gαs via FSHR, promoting the cAMP/protein kinase A (PKA) and calcium pathways to stimulate GSIS, whereas high FSH levels could activate Gαi to inhibit the cAMP/PKA pathway and the amplified effect on GSIS. Our results reveal the role of FSH in regulating pancreatic islet insulin secretion and provide avenues for future clinical investigation and therapeutic strategies for postmenopausal diabetes.

Abstract Structural variations (SVs) and copy number variations (CNVs) contribute to trait variations in fleshy-fruited species. Here, we assemble 10 genomes of genetically diverse Malus accessions, including the ever-green cultivar ‘Granny Smith’ and the widely cultivated cultivar ‘Red Fuji’. Combining with three previously reported genomes, we assemble the pan-genome of Malus species and identify 20,220 CNVs and 317,393 SVs. We also observe CNVs that are positively correlated with expression levels of the genes they are associated with. Furthermore, we show that the noncoding RNA generated from a 209 bp insertion in the intron of mitogen-activated protein kinase homology encoding gene, MMK2, regulates the gene expression and affects fruit coloration. Moreover, we identify overlapping SVs associated with fruit quality and biotic resistance. This pan-genome uncovers possible contributions of CNVs to gene expression and highlights the role of SVs in apple domestication and economically important traits.

Background and aim: Xianglian Wan (XLW) as a classic prescription of traditional Chinese medicine protects digestive function; however, few studies have investigated its anti-colorectal cancer effects. This study verified that the effective monomer berberine of XLW plays an antitumo r role by regulating the acetyl-CoA carboxylase (ACC)/fatty acid synthase (FASN) lipid metabolism-related signaling pathway. Experimental procedure: The connection between XLW and FASN was identified through literature mining, bioinformatics and structural biology. In vivo experiments verified the rationality of the antitumor effect of berberine by regulating the ACC/FASN pathway, and in vitro experiments verified the regulatory relationship between berberine and FASN. Results and conclusion: The most frequent Chinese medicine component in XLW was Coptis chinensis. Berberine, the active ingredient of XLW, has a FASN binding site. FASN expression is higher in tumor tissues than in normal tissues. FASN is related to colorectal adenocarcinoma occurrence and patient survival time. Experiments showed that XLW, berberine and orlistat (FASN inhibitor) can cooperate with palmitic acid (PA) to inhibit tumors in mice. Berberine can downregulate FASN and ACC expression in tumor tissues and inhibit the increase in acetyl-CoA, the intermediate product of exogenous PA intake. The mechanism by which berberine inhibits colon cancer cell proliferation by lowering lipids is related to its downregulation of FASN protein expression. The ACC/FASN signaling pathway is a critical pathway through which berberine, the effective monomer of XLW, plays an antitumor role in colon cancer.

Abstract Aims Chronic heart failure (CHF) remains a major health issue worldwide. In the present study, we aimed to identify novel circulating biomarkers for CHF using serum proteomics technology and to validate the biomarker in three independent cohorts. Methods and results The isobaric tags for relative and absolute quantitation technology was utilized to identify the potential biomarkers of CHF. The validation was conducted in three independent cohort. Cohort A included 223 patients with ischaemic heart disease (IHD) and 321 patients with ischaemic heart failure (IHF) from the CORFCHD‐PCI study. Cohort B recruited 817 patients with IHD and 1139 patients with IHF from the PRACTICE study. Cohort C enrolled 559 non‐ischaemic heart disease patients with CHF (n = 316) or without CHF (n = 243). We found the expression of a‐1 antitrypsin (AAT) was elevated significantly in patients with CHF compared with that in the patients with stable IHD using statistical and bioinformatics analyses. In a validation study, there was a significant difference between patients with stable IHD and patients with IHF in AAT concentration either in cohort A (1.35 ± 0.40 vs. 1.64 ± 0.56, P

Background: Since April 2022, a notable increase in COVID-19 cases with the rapid spread of the SARS-CoV-2 Omicron variant has been reported in Taiwan. In the epidemic, children were one of the most vulnerable groups, so we analyzed their clinical presentations and factors associated with severe complications of COVID-19 in children. Methods: We included hospitalized patients under 18 years old with lab-confirmed SARS-CoV-2 infection from March 1, 2022, to July 31, 2022. We collected the demographic and clinical characteristics of the patients. Patients requiring intensive care were defined as severe cases. Results: Among the 339 enrolled patients, the median age was 31 months (interquartile range (IQR), 8–79.0 months); and 96 patients (28.3%) had underlying diseases. Fever was noted in 319 patients (94.1%) with a median duration of two days (IQR 2–3 days). Twenty-two patients (6.5%) were severe cases, including 10 patients (2.9%) with encephalopathy with abnormal neuroimaging and ten patients (2.9%) with shock. Two patients (0.6%) died. Patients with congenital cardiovascular disease (aOR: 21.689), duration of fever up to four days or more (aOR: 6.466), desaturation (aOR: 16.081), seizure (aOR: 20.92), and procalcitonin >0.5 ng/mL (aOR: 7.886) had a higher risk of severe COVID-19. Conclusions: Vital signs need close monitoring, early management and/or intensive care may be applied in COVID-19 patients with congenital cardiovascular diseases, fever lasting ≥4 days, seizures, desaturation and/or elevated procalcition since they are at higher risks of severe diseases.

Abstract In the field of Science, Technology, Engineering, and Mathematics (STEM) education, which aims to cultivate problem-solving skills, accurately assessing learners' engagement remains a significant challenge. We present a solution to this issue with the Real-time Automated STEM Engagement Detection System (RASEDS). This innovative system capitalizes on the power of artificial intelligence, computer vision, and the Interactive, Constructive, Active, and Passive (ICAP) framework. RASEDS uses You Only Learn One Representation (YOLOR) to detect and map learners' interactions onto the four levels of engagement delineated in the ICAP framework. This process informs the system's recommendation of adaptive learning materials, designed to boost both engagement and self-efficacy in STEM activities. Our study affirms that RASEDS accurately gauges engagement, and that the subsequent use of these adaptive materials significantly enhances both engagement and self-efficacy. Importantly, our research suggests a connection between elevated self-efficacy and increased engagement. As learners become more engaged in their learning process, their confidence is bolstered, thereby augmenting self-efficacy. We underscore the transformative potential of AI in facilitating adaptive learning in STEM education, highlighting the symbiotic relationship between engagement and self-efficacy.

Abstract Background The real-world data of long-term protection under moderate vaccination coverage is limited. This study aimed to evaluate varicella epidemiology and the long-term effectiveness under moderate coverage levels in Ganyu District, Lianyungang City, Jiangsu Province. Methods This was a population-based, retrospective birth cohort study based on the immunization information system (IIS) and the National Notifiable Disease Surveillance System (NNDSS) in Ganyu District. Varicella cases reported from 2009 to 2020 were included to describe the epidemiology of varicella, and eleven-year consecutive birth cohorts (2008–2018) were included to estimate the vaccine effectiveness (VE) of varicella by Cox regression analysis. Results A total of 155,232 native children and 3,251 varicella cases were included. The vaccination coverage was moderate with 37.1%, correspondingly, the annual incidence of varicella infection increased 4.4-fold from 2009 to 2020. A shift of the varicella cases to older age groups was observed, with the peak proportion of cases shifting from 5–6 year-old to 7–8 year-old. The adjusted effectiveness of one dose of vaccine waned over time, and the adjusted VE decreased from 72.9% to 41.8% in the one-dose group. Conclusions The insufficient vaccination coverage (37.1%) may have contributed in part to the rising annual incidence of varicella infection, and a shift of varicella cases to older age groups occurred. The effectiveness of one dose of varicella vaccine was moderate and waned over time. It is urgent to increase varicella vaccine coverage to 80% to reduce the incidence of varicella and prevent any potential shift in the age at infection in China.

Purpose: The study aims to compare the efficacy and safety of a new minimally invasive osteosynthesis technique with those of conventional open surgery for transverse patellar fractures. Methods: It was a retrospective study. Adult patients with closed transverse patellar fracture were included, and with open comminuted patellar fracture were excluded. These patients were divided into minimally invasive osteosynthesis technique (MIOT) group and open reduction and internal fixation (ORIF) group. Surgical time, frequency of intraoperative fluoroscopy, visual analogue scale score, flexion, extension, Lysholm knee score, infection, malreduction, implant migration and implant irritation in two groups were recorded and compared. Statistical analysis was performed by the SPSS software package (version 19). A p

Abstract Objective As of 2022, 36 anti‐seizure medications (ASMs) have been licensed for the treatment of epilepsy, however, adverse effects (AEs) are commonly reported. Therefore, ASMs with a wide margin between therapeutic effects and AEs are preferred over ASMs that are associated with a narrow margin between efficacy and risk of AEs. E2730 was discovered using in vivo phenotypic screening and characterized as an uncompetitive, yet selective, inhibitor of γ‐aminobutyric acid (GABA) transporter 1 (GAT1). Here, we describe the preclinical characteristics of E2730. Methods Anti‐seizure effects of E2730 were evaluated in several animal models of epilepsy: corneal kindling, 6 Hz–44 mA psychomotor seizure, amygdala kindling, Fragile X syndrome, and Dravet syndrome models. Effects of E2730 on motor coordination were assessed in accelerating rotarod tests. The mechanism of action of E2730 was explored by [3H]E2730 binding assay. The GAT1‐selectivity over other GABA transporters was examined by GABA uptake assay of GAT1, GAT2, GAT3, or betaine/GABA transporter 1 (BGT‐1) stably expressing HEK293 cells. To further investigate the mechanism for E2730‐mediated inhibition of GAT1, in vivo microdialysis and in vitro GABA uptake assays were conducted under conditions of different GABA concentrations. Results E2730 showed anti‐seizure effects in the assessed animal models with an approximately >20‐‍fold margin between efficacy and motor incoordination. [3H]E2730 binding on brain synaptosomal membrane was abolished in GAT1‐deficient mice, and E2730 selectively inhibited GAT1‐mediated GABA uptake over other GABA transporters. In addition, results of GABA uptake assays showed that E2730‐mediated inhibition of GAT1 positively correlated to the level of ambient GABA in vitro. E2730 also increased extracellular GABA concentration in hyperactivated conditions but not under basal levels in vivo. Significance E2730 is a novel, selective, uncompetitive GAT1 inhibitor, which acts selectively under the condition of increasing synaptic activity, contributing to a wide margin between therapeutic effect and motor incoordination.