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Abstract Background The prevalence and severity of pediatric Mycoplasma pneumoniae pneumonia (MPP) poses a significant threat to the health and lives of children. In this study, we aim to systematically evaluate the value of routine blood parameters in predicting MPP and develop a robust and generalizable ensemble artificial intelligence (AI) model to assist in identifying patients with MPP. Methods We collected 27 features, including routine blood parameters and hs-CRP levels, from patients admitted to The Affiliated Dazu’s Hospital of Chongqing Medical University with or without MPP between January, 2023 and January, 2024. A classification model was built using seven machine learning (ML) algorithms to develop an integrated prediction tool for diagnosing MPP. It was evaluated on both an internal validation set (982 individuals) and an external validation set (195 individuals). The primary outcome measured the accuracy of the model in predicting MPP. Results The GBDT is state-of-the-art based on 27 features. Following inter-laboratory cohort testing, the GBDT demonstrated an AUC, accuracy, specificity, sensitivity, PPV, NPV, and F1-score of 0.980 (0.938–0.995), 0.928 (0.796–0.970), 0.929 (0.717-1.000), 0.926 (0.889–0.956), 0.922 (0.727-1.000), 0.937 (0.884–0.963), and 0.923 (0.800-0.966) in stratified 10-fold cross-validation. A GBDT-based AI Lab was developed to facilitate the healthcare providers in remote and impoverished areas. Conclusions The GBDT-based AI Lab tool, with high sensitivity and specificity, could help discriminate between pediatric MPP infection and non-MPP infection based on routine blood parameters. Moreover, a user-friendly webpage tool for AI Lab could facilitate healthcare providers in remote and impoverished areas where advanced technologies are not accessible.

Abstract The benefits of physical exercise on human health make it desirable to identify new approaches that would mimic or potentiate the effects of exercise to treat metabolic diseases. However, whether far-infrared (FIR) hyperthermia therapy could be used as exercise mimetic to realize wide-ranging metabolic regulation, and its underling mechanisms remain unclear. Here, a specific far-infrared (FIR) rays generated from graphene-based hyperthermia devices might promote exercise capacity and metabolisms. The material characterization showed that the graphene synthesized by chemical vapour deposition (CVD) was different from carbon fiber, with single-layer structure and high electrothermal transform efficiency. The emission spectra generated by graphene-FIR device would maximize matching those adsorbed by tissues. Graphene-FIR enhanced both core and epidermal temperatures, leading to increased blood flow in the femoral muscle and the abdominal region. The combination of microbiomic and metabolomic analysis revealed that graphene-FIR modulates the metabolism of the gut-muscle axis. This modulation was characterized by an increased abundance of short-chain fatty acids (SCFA)-producing bacteria and AMP, while lactic acid levels decreased. Furthermore, the principal routes involved in glucose metabolism, such as glycolysis and gluconeogenesis, were found to be altered. Graphene-FIR managed to stimulate AMPK activity by activating GPR43, thus enhancing muscle glucose uptake. Furthermore, a microbiota disorder model also demonstrated that the graphene-FIR effectively restore the exercise endurance with enhanced p-AMPK and GLUT4. Our results provided convincing evidence that graphene-based FIR therapy promoted exercise capacity and glucose metabolism via AMPK in gut-muscle axis. These novel findings regarding the therapeutic effects of graphene-FIR suggested its potential utility as a mimetic agent in clinical management of metabolic disorders.

Abstract Twisted trunks are not uncommon in trees, but their effects on tree growth are still unclear. Among coniferous tree species, the phenomenon of trunk distortion is more prominent in Pinus yunnanensis. To expand the germplasm of genetic resources, we selected families with excellent phenotypic traits to provide material for advanced generation breeding. The progeny test containing 93 superior families (3240 trees) was used as the research material. Phenotypic measurements and estimated genetic parameters (family heritability, realistic gain and genetic gain) were performed at 9, 15, and 18 years of age, respectively. The genetic evaluation yielded the following results (1) The intra-family variance component of plant height (PH) was greater than that of the inter-family, while the inter-family variance components of other traits (diameter at breast height (DBH), crown diameter (CD), height under branches (HUB), degree of stem-straightness (DS)) were greater than that of the intra-family, indicating that there was abundant variation among families and potential for selection. (2) At half rotation period (18 years old), there was a significant correlation among the traits. The proportion of trees with twisted trunks (level 1–3 straightness) reached 48%. The DS significantly affected growth traits, among which PH and DBH were the most affected. The volume loss rate caused by twisted trunk was 18.06-56.75%, implying that trunk distortion could not be completely eliminated after an artificial selection. (3) The influence of tree shape, crown width, and trunk on volume increased, and the early-late correlation between PH, DBH and volume was extremely significant. The range of phenotypic coefficient of variation, genetic variation coefficient and family heritability of growth traits (PH, DBH, and volume) were 44.29-127.13%, 22.88-60.87%, and 0.79–0.83, respectively. (4) A total of 21 superior families were selected by the method of membership function combined with independent selection. Compared with the mid-term selection (18 years old), the accuracy of early selection (9 years old) reached 77.5%. The selected families’ genetic gain and realistic gain range were 5.79-19.82% and 7.12-24.27%, respectively. This study can provide some useful reference for the breeding of coniferous species.

Abstract Background Neutrophils play an essential role in Alzheimer’s disease (AD) pathology. However, the extent of their heterogeneity remains poorly explored, particularly in the context of developing novel therapies targeting these cells. Results We investigate the population structure of neutrophils purified from peripheral blood samples of AD mice. Utilizing single cell RNA sequencing, we comprehensively map neutrophil populations into six distinct clusters and find that the Neu-5 subset is specially enriched in AD mice. This subset exhibits fewer specific granules and a lower mature score. Gene ontology (GO) analysis reveals that genes involved in cytokine-mediated signaling are downregulated in the Neu-5 cluster. Furthermore, we identify the Ccrl2 gene is specifically upregulated in this subgroup, which is confirmed by flow cytometry in AD mice. Finally, immunohistochemical staining indicates that CCRL2 protein is increased in the brains of AD mice. Conclusions We identify a unique CCRL2 positive neutrophil cluster, that is specifically enriched in the peripheral blood of AD mice.

Abstract Droplet Interface Bilayers (DIBs) constitute a commonly used model of artificial membranes for synthetic biology research applications. However, their practical use is often limited by their requirement to be surrounded by oil. Here we demonstrate in-situ bilayer manipulation of submillimeter, hydrogel-encapsulated droplet interface bilayers (eDIBs). Monolithic, Cyclic Olefin Copolymer/Nylon 3D-printed microfluidic devices facilitated the eDIB formation through high-order emulsification. By exposing the eDIB capsules to varying lysophosphatidylcholine (LPC) concentrations, we investigated the interaction of lysolipids with three-dimensional DIB networks. Micellar LPC concentrations triggered the bursting of encapsulated droplet networks, while at lower concentrations the droplet network endured structural changes, precisely affecting the membrane dimensions. This chemically-mediated manipulation of enclosed, 3D-orchestrated membrane mimics, facilitates the exploration of readily accessible compartmentalized artificial cellular machinery. Collectively, the droplet-based construct can pose as a chemically responsive soft material for studying membrane mechanics, and drug delivery, by controlling the cargo release from artificial cell chassis.

In this experiment, goat milk casein was used as raw material. Goat milk casein was treated with different ultrasonic intensities to explore the effects of ultrasonic treatment on the pH, conductivity, Zeta potential, turbidity and other physical and chemical indexes, as well as the functional characteristics of emulsification and foaming. The results showed that compared with untreated group, after ultrasonic treatment, the pH decreased and the conductivity had no significant change (P>0.05). The absolute value of Zeta potential reached the maximum value of 27.85±1.55 mV when treated at 400 W for 2 min. Turbidity was significantly decreased compared with untreated group (P

AIM: To evaluate the effect of low-degree astigmatism on objective visual quality through the Optical Quality Analysis System (OQAS). METHODS: This study enrolled 46 participants (aged 23 to 30y, 90 eyes) with normal or corrected-to-normal vision. The cylindrical lenses (0, 0.5, 0.75, 1.0, and 1.25 D) were placed at the axial direction (180°, 45°, 90°, and 135°) in front of the eyes with the best correction to form 16 types of regular low-degree astigmatism. OQAS was used to detect the objective visual quality, recorded as the objective scattering index (OSI), OQAS values at contrasts of 100%, 20%, and 9% predictive visual acuity (OV100%, OV20%, and OV9%), modulation transfer function cut-off (MTFcut-off) and Strehl ratio (SR). The mixed effect linear model was used to compare objective visual quality differences between groups and examine associations between astigmatic magnitude and objective visual quality parameters. RESULTS: Apparent negative relationships between the magnitude of low astigmatism and objective visual quality were observed. The increase of OSI per degree of astigmatism at 180°, 45°, 90°, and 135° axis were 0.38 (95%CI: 0.35, 0.42), 0.50 (95%CI: 0.46, 0.53), 0.49 (95%CI: 0.45, 0.54) and 0.37 (95%CI: 0.34, 0.41), respectively. The decrease of MTFcut-off per degree of astigmatism at 180°, 45°, 90°, and 135° axis were -10.30 (95%CI: -11.43, -9.16), -12.73 (95%CI: -13.62, -11.86), -12.75 (95%CI: -13.79, -11.70), and -9.97 (95%CI: -10.92, -9.03), respectively. At the same astigmatism degree, OSI at 45° and 90° axis were higher than that at 0° and 135° axis, while MTFcut-off were lower. CONCLUSION: Low astigmatism of only 0.50 D can significantly reduce the objective visual quality.

The accurate identification and positioning of the anchor position of the coal mine tunneling roadway is the key technology that the drilling anchor robot urgently needs to break through to achieve intelligent permanent support. An intelligent identification and positioning method for roadway anchor hole position based on visual image and laser point cloud fusion is proposed, which includes three steps: image target recognition, point cloud image feature fusion, and positioning coordinate extraction: ① In order to solve the problem of blurred image of anchor hole contour caused by environmental factors such as low illumination, water mist and dust in coal mines, the IA (Image-Adaptive)-SimAM-YOLOv7-tiny network was used to visually identify the position of the anchor hole to be anchored in the roadway, which can adaptively enhance the image brightness and contrast, recover the high-frequency information at the edge of the anchor hole, and make the model focus on the characteristics of the anchor hole, so as to improve the success rate of anchor hole detection; ② The Region of Interest (ROI) of image detection is generated by perspective projection relationship to generate a cone-shaped area of interest to obtain the corresponding target point cloud cluster; ③ The point cloud processing algorithm is used to extract the anchor hole boundary point cloud, obtain the central coordinates of the hole position and its normal vector, and judge the correctness of the anchor hole recognition by comparing the coordinate depth difference. In this paper, a drilling and positioning system for bolting trolley manipulator is built to verify the accuracy and accuracy of the algorithm's autonomous positioning, and the experimental results show that the mean average precision (mAP) of the IA-SimAM-YOLOv7-tiny model is 87.3%, which is 4.6% higher than that of the YOLOv7-tiny model. Compared with the single vision method, the fusion algorithm proposed in this paper has a positioning error of 3 mm, and the average recognition time of the system in the case of a single anchor hole is 0.77 s, compared with the single vision method, the fusion of laser and visual multi-source can not only reduce the influence of environment and small sample training on positioning performance, but also obtain the normal vector of the anchor hole position, which provides a basis for the manipulator to adjust the drilling posture to achieve accurate anchoring.

Abstract Objective To describe how mental health and sleep status influence the health-related quality of life (HRQOL) of people living with HIV/AIDS (PLWHA) during the novel coronavirus disease 2019 (COVID-19) pandemic, and to apply targeted interventions to improve the HRQOL. Methods A web-based online questionnaire survey was administered. Descriptive analysis was used to depict the mental health and sleep status. Correlation analysis and the structural equation model (SEM) method were used to analyze the influence of mental health and sleep status on HRQOL in PLWHA. Results After excluding 24 unqualified questionnaires, a total of 490 participants in this survey were included in the statistical analysis. Of the participants, 66.1% and 55.1% reported mild or worse symptoms of depression and anxiety, respectively. Overall, 70.0% had varying degrees of sleep problems. Correlation analysis showed that anxiety had the strongest correlation with sleep disturbances and sleep quality (R = 0.588 and 0.551, respectively), while depression had the strongest correlation with the HRQOL psychological and physical domains (R = − 0.759 and − 0.682, respectively). SEM analysis showed that depression, sleep quality, and psychological domains had the greatest item load on mental health, sleep status, and HRQOL (093, 0.82, and 0.89, respectively). Mental health had a more significant influence than sleep status on HRQOL, as indicated by factor loading (− 0.75 and − 0.15, respectively). Conclusions There were more severe mental health and sleep problems among PLWHA during the COVID-19 pandemic, thus, mental health intervention, especially to relieve depression symptoms, may be the most important approach to improve the HRQOL among PLWHA.

Abstract This article proposes a method to effectively suppress second‐harmonic current (SHC) of dual active bridge (DAB) converter, which adopts the triple‐phase shift (TPS) modulation strategy, in two‐stage single‐phase inverter system. Load current feedforward control with twice the output voltage frequency notch filter inserted is introduced to ensure the dynamic response performance. The averaged model of the system is established to analyse the influence of output impedance of front‐end DAB converter on SHC from the perspective of impedance. The proposed method does not need to consider the accuracy of the intermediate bus capacitance. Finally, an experimental prototype was established to verify the correctness and effectiveness of the proposed SHC reduction method.

Abstract Background Recent studies showed heterogeneity in stage IVB patients. However, few studies focused on the prognosis of supraclavicular metastatic ovarian cancer. This study aimed to explore the prognostic factors and the role of primary debulking in IVB ovarian cancer patients with supraclavicular lymph node metastasis. Methods We retrospectively analyzed patients newly diagnosed as primary epithelial ovarian cancer with supraclavicular lymph node metastasis from January 2015 to July 2020. Supraclavicular lymph node metastasis was defined as either the pathological diagnosis by supraclavicular lymph node biopsy, or the radiological diagnosis by positron emission tomography-computed tomography (PET-CT). Results In 51 patients, 37 was diagnosed with metastatic supraclavicular lymph nodes by histology, 46 by PET-CT, and 32 by both methods. Forty-four (86.3%) with simultaneous metastatic paraaortic lymph nodes (PALNs) by imaging before surgery or neoadjuvant chemotherapy were defined as “continuous-metastasis type”, while the other 7 (13.7%) defined as “skip-metastasis type”. Nineteen patients were confirmed with metastatic PALNs by histology. Thirty-four patients were investigated for BRCA mutation, 17 had germline or somatic BRCA1/2 mutations (g/sBRCAm). With a median follow-up of 30.0 months (6.3–63.4 m), 16 patients (31.4%) died. The median PFS and OS of the cohort were 17.3 and 48.9 months. Survival analysis showed that “continuous-metastasis type” had longer OS and PFS than “skip-metastasis type” (OS: 50.0/26.6 months, PFS: 18.5/7.2months, p=0.005/0.002). BRCA mutation carriers also had longer OS and PFS than noncarriers (OS: 57.4 /38.5 m, p=0.031; PFS: 23.6/15.2m, p=0.005). Multivariate analysis revealed only metastatic PALNs was independent prognostic factor for OS (p=0.040). Among “continuous-metastasis type” patients, 22 (50.0%) achieved R0 abdominopelvic debulking, who had significantly longer OS (55.3/42.3 months, p =0.034) than those with residual abdominopelvic tumors. Conclusions In stage IVB ovarian cancer patients with supraclavicular lymph nodes metastasis, those defined as “continuous-metastasis type” with positive PALNs had better prognosis. For them, optimal abdominopelvic debulking had prognostic benefit, although metastatic supraclavicular lymph nodes were not resected. Higher BRCA mutation rate than the general population of ovarian cancer patients was observed in patients with IVB supraclavicular lymph node metastasis, leading to better survival as expected.

Abstract Cimicifugae Rhizoma, generally known as “Sheng Ma” in China, has great medicinal and dietary values. Cimicifugae Rhizoma is the dried rhizome of Cimicifuga foetida L., Cimicifuga dahurica (Turcz.) Maxim. and Cimicifuga heracleifolia Kom., which has been used to treat wind-heat headache, tooth pain, aphtha, sore throat, prolapse of anus and uterine prolapse in traditional Chinese medicine. This review systematically presents the traditional uses, phytochemistry, pharmacology, clinical studies, quality control and toxicity of Cimicifugae Rhizoma in order to propose scientific evidence for its rational utilization and product development. Herein, 348 compounds isolated or identified from the herb are summarized in this review, mainly including triterpenoid saponins, phenylpropanoids, chromones, alkaloids, terpenoids and flavonoids. The crude extracts and its constituents had various pharmacological properties such as anti-inflammatory, antitumor, antiviral, antioxidant, neuroprotective, anti-osteoporosis and relieving menopausal symptoms. The recent research progress of Cimicifugae Rhizoma in ethnopharmacology, phytochemistry and pharmacological effects demonstrates the effectiveness of its utilization and supplies valuable guidance for further research. This review will provide a basis for the future development and utilization of Cimicifugae Rhizoma.

With the use of metagenomic next-generation sequencing, patients diagnosed with Whipple pneumonia are being increasingly correctly diagnosed. We report a series of 3 cases in China that showed a novel pattern of movable infiltrates and upper lung micronodules. After treatment, the 3 patients recovered, and lung infiltrates resolved.

We report a clinical isolate of Burkholderia thailandensis 2022DZh obtained from a patient with an infected wound in southwest China. Genomic analysis indicates that this isolate clusters with B. thailandensis BPM, a human isolate from Chongqing, China. We recommend enhancing monitoring and surveillance for B. thailandensis infection in both humans and livestock.

Abstract Single-frame infrared small target detection is affected by the low image resolution and small target size, and is prone to the problems of small target feature loss and positional offset during continuous downsampling; at the same time, the sparse features of the small targets do not correlate well with the global-local linkage of the background features. To solve the above problems, this paper proposes an efficient infrared small target detection method. First, this paper incorporates BlurPool in the feature extraction part, which reduces the loss and positional offset of small target features in the process of convolution and pooling. Second, this paper designs an interactive attention deep feature fusion module, which acquires the correlation information between the target and the background from a global perspective, and designs a compression mechanism based on deep a priori knowledge, which reduces the computational difficulty of the self-attention mechanism. Then, this paper designs the context local feature enhancement and fusion module, which uses deep semantic features to dynamically guide shallow local features to realize enhancement and fusion. Finally, this paper proposes an edge feature extraction module for shallow features, which utilizes the complete texture and location information in the shallow features to assist the network to initially locate the target position and edge shape. Numerous experiments show that the method in this paper significantly improves nIoU, F1-Measure and AUC on IRSTD-1k Datasets and NUAA-SIRST Datasets.

Abstract Background Non-alcoholic fatty liver disease (NAFLD), often linked with obesity, can also affect individuals with normal weight, a condition known as “lean NAFLD”, imposing comparable burdens and adverse effects. However, the impact of diet on lean NAFLD remains underexplored. The objective of this study is to investigate the correlation between the Dietary Inflammatory Index (DII) and NAFLD among Americans, stratified by waist-to-height ratio (WHtR) and body mass index (BMI). Methods Five thousand one hundred fifty-two participants from the National Health and Nutrition Examination Survey (NHANES) 2003–2018 were comprised in the final analysis. NAFLD and advanced liver fibrosis were diagnosed by serological markers. Lean and abdominal lean individuals were identified using BMI and WHtR, separately. DII was determined by assigning scores to 28 distinct food parameters based on their inflammatory potential, obtained from the NAHNES website. Differences across DII quartiles were evaluated using the Kruskal-Wallis H Test, Chi-Square Test along with One-Way ANOVA. The correlation between DII and NAFLD was determined by multiple regression models and subgroup analyses. Results Among the 5152 subjects, 2503 were diagnosed with NAFLD, including 86 cases of lean NAFLD and 8 cases of abdominal lean NAFLD. DII was positively linked with NAFLD (Odds Ratio (OR) = 1.81 [1.48–2.21], P 0.50, OR = 1.48 [1.23–1.79], P

Abstract Objective Many acupuncture acupoints are located on the posterior midline of the neck region. The needling depth for acupuncture is important for practitioners, and an unsafe needling depth increases the possibility of damage to the spinal cord and brainstem. Can the safety of acupuncture be assessed by examining bone structures? We focused on this aim to carry out this study. Methods The shortest distance from the posterior border of the foramen magnum to the line joining both upper ends of the posterior border of the mastoid process was measured on 29 skulls. Distances from the posterior border of the vertebral foramen to the tip of the spinous process and posterior tubercle of the atlas were measured and evaluated from 197 dry cervical vertebrae and 31 lateral cervical radiographs of patient subjects. The anatomic relationships of the vertebral canal with the external occipital protuberance, tip of the spinous process of the axis, tip of the posterior tubercle of the atlas, and upper end of the posterior border of the mastoid process were observed and evaluated via lateral cervical radiography. Results The shortest distance from the foramen magnum to the line between the mastoid processes was 4.65±1.75 mm, and the distance from the superior border of the vertebral foramen of the atlas to the posterior tubercle was less than the distance from the inferior border. The distance from the superior border of the vertebral canal to the tip of the spinous process in C2-C7 was greater than the distance from the inferior border. The mean lengths of the superior border of the C2 spinous process and the inferior border of the C7 spinous process were greater than 21 mm and 31 mm, respectively. The line from the upper end of the posterior border of the mastoid process to the tip of the C2 spinous process or 10 mm deep to the tip of the C2 spinous process was posterior to the vertebral canal. Conclusions On the posterior midline of the neck region between the tip of spinous process of axis and external occipital protuberance, if the needle reaches the depth of the line between the upper end of posterior border of mastoid process and the tip of the spinous process of the axis, approximately 10 mm along the spinous process of the axis, the needle is in the safe region. The mean length of the C2-C7 spinous process is suitable to accommodate the needling depth of the adjacent acupoint. Bone structures can be used to effectively assess the safety of acupuncture on the posterior midline of the neck region.

Abstract Background B-box (BBX) proteins are a type of zinc finger proteins containing one or two B-box domains. They play important roles in development and diverse stress responses of plants, yet their roles in wheat remain unclear. Results In this study, 96 BBX genes were identified in the wheat genome and classified into five subfamilies. Subcellular localization prediction results showed that 68 TaBBXs were localized in the nucleus. Protein interaction prediction analysis indicated that interaction was one way that these proteins exerted their functions. Promoter analysis indicated that TaBBXs may play important roles in light signal, hormone, and stress responses. qRT-PCR analysis revealed that 14 TaBBXs were highly expressed in seeds compared with other tissues. These were probably involved in seed dormancy and germination, and their expression patterns were investigated during dormancy acquisition and release in the seeds of wheat varieties Jing 411 and Hongmangchun 21, showing significant differences in seed dormancy and germination phenotypes. Subcellular localization analysis confirmed that the three candidates TaBBX2-2 A, TaBBX4-2 A, and TaBBX11-2D were nuclear proteins. Transcriptional self-activation experiments further demonstrated that TaBBX4-2A was transcriptionally active, but TaBBX2-2A and TaBBX11-2D were not. Protein interaction analysis revealed that TaBBX2-2A, TaBBX4-2A, and TaBBX11-2D had no interaction with each other, while TaBBX2-2A and TaBBX11-2D interacted with each other, indicating that TaBBX4-2A may regulate seed dormancy and germination by transcriptional regulation, and TaBBX2-2A and TaBBX11-2D may regulate seed dormancy and germination by forming a homologous complex. Conclusions In this study, the wheat BBX gene family was identified and characterized at the genomic level by bioinformatics analysis. These observations provide a theoretical basis for future studies on the functions of BBXs in wheat and other species.

Abstract Protein kinases become an important source of potential drug targets. Developing new, efficient, and safe small-molecule kinase inhibitors has become an important topic in the field of drug research and development. In contrast with traditional wet experiments which are time-consuming and expensive, machine learning-based approaches for predicting small molecule inhibitors for protein kinases are time-saving and cost-effective, which are highly desired for us. However, the issue of sample scarcity (known active and inactive compounds are usually limited for most kinases) poses a challenge to the research and development of machine learning-based kinase inhibitors' active prediction methods. To alleviate the data scarcity problem in the prediction of kinase inhibitors, in this study, we present a novel Meta-learning-based inductive logistic matrix completion method for the Prediction of Kinase Inhibitors (MetaILMC). MetaILMC adopts a meta-learning framework to learn a well-generalized model from tasks with sufficient samples, which can fast adapt to new tasks with limited samples. As MetaILMC allows the effective transfer of the prior knowledge learned from kinases with sufficient samples to kinases with a small number of samples, the proposed model can produce accurate predictions for kinases with limited data. Experimental results show that MetaILMC has excellent performance for prediction tasks of kinases with few-shot samples and is significantly superior to the state-of-the-art multi-task learning in terms of AUC, AUPR, etc., various performance metrics. Case studies also provided for two drugs to predict Kinase Inhibitory scores, further validating the proposed method's effectiveness and feasibility. Scientific contribution Considering the potential correlation between activity prediction tasks for different kinases, we propose a novel meta learning algorithm MetaILMC, which learns a prior of strong generalization capacity during meta-training from the tasks with sufficient training samples, such that it can be easily and quickly adapted to the new tasks of the kinase with scarce data during meta-testing. Thus, MetaILMC can effectively alleviate the data scarcity problem in the prediction of kinase inhibitors.

Abstract Background Mechanosensitive ion channel PIEZOs have been widely reported to involve inflammation and pain. This study aimed to clarify expression patterns of PIEZOs and their potential relations to irreversible pulpitis. Materials and methods Normal pulp tissues (n = 29) from patients with impacted third molars and inflamed pulp tissues (n = 23) from patients with irreversible pulpitis were collected. Pain levels were assessed using a numerical rating scale. PIEZO expressions were measured using real-time PCR and then confirmed using GEO datasets GSE77459, immunoblot, and immunohistochemistry staining. Correlations of PIEZO mRNA expression with inflammatory markers, pain markers, or clinical pain levels were evaluated using Spearman’s correlation analysis. Univariate analysis was conducted to analyze PIEZO expressions based on pain description and clinical examinations of cold test, percussion, palpation, and bite test. Results Compared with normal pulp tissues, mRNA expression levels of PIEZO1 were significantly increased in inflamed pulp tissues, while PIEZO2 was significantly decreased, which was further confirmed in GSE77459 and on a protein and histological level. The positive correlation of the mRNA expression levels between PIEZO1 and inflammatory markers, as well as between PIEZO2 and pain markers, was verified. PIEZO2 expression was also positively correlated with pain levels. Besides, irreversible pulpitis patients who reported continuous pain and who detected a positive response to cold stimulus exhibited a higher expression level of PIEZO2 in the inflamed pulp tissues. By contrast, patients reporting pain duration of more than one week showed a higher expression level of PIEZO1. Conclusions This study demonstrated the upregulation of PIEZO1 and the downregulation of PIEZO2 in irreversible pulpitis and revealed the potential relation of PIEZO1 and PIEZO2 to inflammation and pain. These findings suggested that PIEZOs might play critical roles in the progression of irreversible pulpitis and paved the way for further investigations aimed at novel therapies of irreversible pulpitis by targeting PIEZOs.

Abstract Background Transforming growth factor-β (TGF-β) is a cytokine with multiple functions, including cell growth regulation, extracellular matrix production, angiogenesis homeostasis adjustment and et al. TGF-β pathway activation promotes tumor metastasis/progression and mediates epithelial-mesenchymal transmission suppressing immunosurveillance in advanced tumors. GFH018, a small molecule inhibitor blocking TGF-β signal transduction, inhibits the progression and/or metastasis of advanced cancers. This first-in-human study evaluated the safety, tolerability, pharmacokinetics (PK), and efficacy of GFH018 monotherapy in patients with advanced solid tumors. Methods This phase I, open-label, multicenter study used a modified 3+3 dose escalation and expansion design. Adult patients with advanced solid tumors failing the standard of care were enrolled. Starting at 5 mg, eight dose levels up to 85 mg were evaluated. Patients received GFH018 BID (14d-on/14d-off) starting on the 4th day after a single dose on cycle 1, day 1. Subsequent cycles were defined as 28 days. The study also explored the safety of 85 mg BID 7d-on/7d-off. Adverse events were graded using NCI criteria for adverse events (NCI-CTCAE v5.0). PK was analyzed using a noncompartmental method. Efficacy was evaluated using RECIST 1.1. Blood samples were collected for biomarker analysis. Results Fifty patients were enrolled and received at least one dose of GFH018. No dose-limiting toxicity occurred, and the maximum tolerated dose was not reached. Forty-three patients (86.0%) had at least one treatment-related adverse event (TRAE), and three patients (6.0%) had ≥ G3 TRAEs. The most common TRAEs (any grade/grade ≥3) were AST increased (18%/0%), proteinuria (14%/2%), anemia (14%/2%), and ALT increased (12%/0%). No significant cardiotoxicity or bleeding was observed. GFH018 PK was linear and dose-independent, with a mean half-life of 2.25–8.60 h from 5 – 85 mg. Nine patients (18.0%) achieved stable disease, and one patient with thymic carcinoma achieved tumor shrinkage, with the maximum target lesion decreased by 18.4%. Serum TGF-β1 levels were not associated with clinical responses. The comprehensive recommended dose for Phase II was defined as 85 mg BID 14d-on/14d-off. Conclusions GFH018 monotherapy presented a favorable safety profile without cardiac toxicity or bleeding. Modest efficacy warrants further studies, including combination strategies. Trial registration ClinicalTrial. gov ( https://www.clinicaltrials.gov/ ), NCT05051241. Registered on 2021-09-02.

Abstract Accumulating evidence suggests that imbalanced oxidative stress (OS) may contribute to the mechanism of schizophrenia. The aim of the present study was to evaluate the associations of OS parameters with psychopathological symptoms in male chronically medicated schizophrenia (CMS) and treatment-resistant schizophrenia (TRS) patients. Levels of hydrogen peroxide (H2O2), hydroxyl radical (·OH), peroxidase (POD), α-tocopherol (α-toc), total antioxidant capacity (TAC), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were assayed in males with CMS and TRS, and matched healthy controls. Schizophrenia symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The results demonstrated significant differences in the variables H2O2 (F = 5.068, p = 0.008), ·OH (F = 31.856, p

Abstract Colorectal cancer (CRC) is a highly prevalent and lethal malignancy worldwide. Although immunotherapy has substantially improved CRC outcomes, intolerance remains a major concern among most patients. Considering the pivotal role of the tumor microenvironment (TME) in tumor progression and treatment outcomes, profiling the TME at the transcriptomic level can provide novel insights for developing CRC treatment strategies. Seventy-seven TME-associated signatures were acquired from previous studies. To elucidate variations in prognosis, clinical features, genomic alterations, and responses to immunotherapy in CRC, we employed a non-negative matrix factorization algorithm to categorize 2595 CRC samples of 27 microarrays from the Gene Expression Omnibus database. Three machine learning techniques were employed to identify a signature specific to immunotherapy. Subsequently, the mechanisms by which this signature interacts with TME subtypes and immunotherapy were investigated. Our findings revealed five distinct TME subtypes (TMESs; TMES1–TMES5) in CRC, each exhibiting a unique pattern of immunotherapy response. TMES1, TMES4, and TMES5 had relatively inferior outcomes, TMES2 was associated with the poorest prognosis, and TMES3 had a superior outcome. Subsequent investigations revealed that activated dendritic cells could enhance the immunotherapy response rate, with their augmentation effect closely associated with the activation of CD8+T cells. We successfully classified CRC into five TMESs, each demonstrating varying response rates to immunotherapy. Notably, the application of machine learning to identify activated dendritic cells helped elucidate the underlying mechanisms contributing to these differences. We posit that these TMESs hold promising clinical implications for prognostic evaluation and guidance of immunotherapy strategies, thereby providing valuable insights to inform clinical decision-making.

Introduction Thyroid cancer stem cells (TCSCs) play a crucial role in the pathogenesis, metastasis, and therapeutic response of thyroid cancer, making them promising biomarkers and potential targets for clinical intervention. This systematic review aims to qualitatively assess the impact of commonly used TCSC markers on the prognosis of thyroid cancer using qualitative methods. Material and methods In total, the analysis encompassed five articles. Results Six TCSC markers were involved, among which CD133, CD44, CD24, CD15 and ALDH1 were associated with the prognosis of thyroid cancer. Conclusions However, the utility of these TCSC markers in clinical practice for predicting the prognosis of thyroid cancer requires further research to provide additional evidence supporting their effectiveness.

Abstract With the evolution of people's consumption habits and the rapid growth of urban logistics, the number of trucks and delivery frequency has increased significantly, exacerbating urban traffic congestion and environmental pollution. Consequently, there is an urgent need to improve the current inefficient and highly polluted distribution mode. Currently, in most cities in China, the metro passenger flow is insufficient, and the capacity is excessive during off-peak hours, resulting in underutilized carriage capacity. The integration of surface and underground transport resources can effectively address these issues and facilitate complementary advantages and win–win cooperation between express companies and metro enterprises. This study proposes an innovative problem of split demand route planning in the cooperative distribution system involving express companies and subways. A cooperative distribution model is developed to minimize the total cost, and solved by the Cuckoo Search algorithm to obtain the optimized solution. The model is applied to the urban rail transit network in Changchun, and the results demonstrate that it is effective in reducing truck mileage and distribution costs. Compared to the single delivery pattern by trucks, the cooperative distribution approach proves to be more cost-effective and environmentally friendly.

Abstract Introduction The replacement intervals for infusion sets may differ among healthcare institutions, which may have an impact on the occurrence of central line-associated bloodstream infections (CLABSI). Nevertheless, there exists a limited amount of high-quality evidence available to assist clinicians in determining the most suitable replacement intervals for infusion sets. Therefore, the objective of this trial is to compare the efficacy of 24-h and 96-h replacement intervals for infusion sets on CLABSI among critically ill adults who have central venous access devices. Methods This is a multicenter, parallel-group randomized controlled trial that will investigate the effect of infusion set replacement intervals on CLABSI in adult patients admitted to intensive care units (ICUs). The study will enroll 1240 participants who meet the inclusion criteria, which includes being 18 years or older, expected to stay in the ICU for longer than 96 h, and in need of central venous access. Participants will be randomly assigned to either a control group receiving a 96-h replacement interval or a treatment group receiving a 24-h replacement interval. Planned Outcome The primary outcome of this trial is the rate of CLABSI within 28 days after randomization. Conclusion This is the first randomized controlled trial to investigate the effects of infusion set replacement at 24-h and 96-h intervals on CLABSI in ICU patients. Trial Registration ClinicalTrials.gov identifier, NCT05359601.

Abstract Background This study evaluates the impact of corneal power on the accuracy of 14 newer intraocular lens (IOL) calculation formulas in cataract surgery. The aim is to assess how these formulas perform across different corneal curvature ranges, thereby guiding more precise IOL selection. Methods In this retrospective case series, 336 eyes from 336 patients who underwent cataract surgery were studied. The cohort was divided into three groups according to preoperative corneal power. Key metrics analyzed included mean prediction error (PE), standard deviation of PE (SD), mean absolute prediction error (MAE), median absolute error (MedAE), and the percentage of eyes with PE within ± 0.25 D, 0.50 D, ± 0.75 D, ± 1.00 D and ± 2.00 D. Results In the flat K group (Km

Abstract The inherent variability of pitting poses challenges in accurately evaluating the pitting resistance due to potential disparities in test results. This study compares the pitting resistance of two commercial 2205 duplex stainless steels. Counterintuitively, the variant with higher Pitting Resistance Equivalent Number, exhibits a lower Critical Pitting Temperature. Through the potentiostatic pulse test and potentiostatic polarization, this variant is observed to have a greater number of pitting initiation sites. Further investigation, using SEM inclusion statistics, reveals an increased presence of inclusions rich in calcium oxides as the underlying cause of this unexpected phenomenon.

Abstract Background Coronary artery disease (CAD) patients who have undergone coronary artery bypass grafting (CABG) often experience a severe psychological burden for a long period of time, which can adversely affect their post-operative prognosis. Therefore, this study aimed to evaluate the effect of a web-based Information-Knowledge-Attitude-Practice (WIKAP) continuous intervention on the psychological status, medical compliance, and quality of life (QoL) in patients with CAD after CABG surgery. Methods A parallel randomized clinical trial enrolled 174 CAD patients who underwent CABG at our hospital between January 2018 and December 2019. The participants were randomly divided into the Control and WIKAP group and received intervention for 12 months. The scores for anxiety, depression, medical compliance, and QoL were assessed on the first day (M0), 3rd month (M3), 6th month (M6), 9th month (M9) and 12th month (M12) after discharge. Furthermore, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was analyzed using the Kaplan-Meier curve and Cox proportional regression models for an additional 24-month follow-up period without any intervention. Results After the 12-month intervention, the scores of anxiety and depression were significantly reduced in the WIKAP group at M9 and M12 compared to those in the Control group (all P 0.05). Cox proportional regression analysis also showed that the nursing intervention (Control vs. WKIAP) was not associated with the incidence of MACCE. Conclusion WIKAP nursing intervention effectively improved the psychological health, medical compliance, and QoL in CAD patients who underwent CABG operation, but it did not prolong MACCE-free survival. Trail registration The study is registered in isrctn.org: ISRCTN13653455.

Abstract A flexible smart coating with electroluminescence effect was designed and fabricated on the surface of gas insulated switch gear (GIS)/gas insulated transmission line (GIL) epoxy insulators based on two‐step curing process. As the AC voltage increases, the luminous area on the insulator surface expands from the centre to the periphery, and the light intensity shows a linear relationship with the applied voltage. Besides, the flexible smart coating can effectively identify the location of metal particle defects and the degree of electric field distortion. The flexible smart coating enhances the surface flashover voltage due to its higher dielectric constant. Simultaneously, metal particle contamination can substantially reduce the insulation performance of epoxy insulators, particularly when they are located near the high‐voltage side. It is hoped that this study can provide a reference for the smart detection of surface defects GIS/GIL basin insulators.

AIM: To investigate the molecular diagnosis of a three-generation Chinese family affected with aniridia, and further to identify clinically a PAX6 missense mutation in members with atypical aniridia. METHODS: Eleven family members with and without atypical aniridia were recruited. All family members underwent comprehensive ophthalmic examinations. A combination of whole exome sequencing (WES) and direct Sanger sequencing were performed to uncover the causative mutation. RESULTS: Among the 11 family members, 8 were clinically diagnosed with congenital aniridia (atypical aniridia phenotype). A rare heterozygous mutation c.622C>T (p.Arg208Trp) in exon 8 of PAX6 was identified in all affected family members but not in the unaffected members or in healthy control subjects. CONCLUSION: A rare missense mutation in the PAX6 gene is found in members of a three-generation Chinese family with congenital atypical aniridia. This result contributes to an increase in the phenotypic spectrum caused by PAX6 missense heterozygous variants and provides useful information for the clinical diagnosis of atypical aniridia, which may also contribute to genetic counselling and family planning.

Abstract Background Sparganosis is a worldwide food-borne parasitic disease caused by spargana infection, which infects the muscle of frogs and snakes as well as many tissues and organs in humans. There are currently no viable treatments for sparganosis. Understanding spargana’s nutrition source and carbohydrate metabolism may be crucial for identifying its energy supply and establishing methods of treatment for sparganosis. Methods Using an amino acid analyzer and nutrient concentration detection kits, we assessed nutrient concentrations in the muscles of Fejervarya limnocharis and Pelophylax plancyi infected or not infected with spargana. Quantitative polymerase chain reaction (PCR) was used to quantify the major enzymes involved in five glucose metabolism pathways of spargana developing in vivo. We also used quantitative PCR to assess key enzymes and transcriptome sequencing to explore the regulation of carbohydrate metabolic pathways in vitro in response to different 24-h food treatments. Results Infected muscle tissues had considerably higher concentrations of glucogenic and/or ketogenic amino acids, glucose, and glycogen than non-infected muscle tissues. We discovered that the number of differentially expressed genes in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was larger in low-glucose than in other dietary groups. We examined differences in the expression of genes producing amino acid transporters, glucose transporters, and cathepsins in spargana grown in various nutritional environments. In the normal saline group, only the major enzymes in the tricarboxylic acid cycle (TCA), glycogenesis, and glycogenolysis pathways were expressed. The l-glutamine group had the greatest transcriptional levels of critical rate-limiting enzymes of gluconeogenesis and glycogenesis. Furthermore, the low-glucose group had the highest transcriptional levels of critical rate-limiting enzymes involved in the TCA, glycolytic, and glycogenolysis pathways. Surprisingly, when compared to the in vitro culturing groups, spargana developing in vivo exhibited higher expression of these critical rate-limiting enzymes in these pathways, with the exception of the pentose phosphate pathway. Conclusions Spargana have a variety of nutritional sources, and there is a close relationship between nutrients and the carbohydrate metabolism pathways. It takes a multi-site approach to block nutrient absorption and carbohydrate metabolism pathways to provide energy to kill them. Graphical Abstract

Abstract Background Family doctor contract services (FDCS) have been introduced in China in 2009 [1] and rapidly expanded recently. This study sought to investigate factors that influenced the willingness of Chinese residents to use FDCS. Methods We employed multistage stratified and convenience sampling to administer questionnaires to 1455 Beijing, Qinghai, and Fujian residents. The willingness of residents in each province to contract family doctors was analyzed using the chi-square test and binary logistic regression. Results The analysis in this study found that the signing rate of family doctors in China was about 27.77%, with differences in the signing up levels in Beijing (13.68%), Fujian (64.49%) and Qinghai (11.22%). In addition, the binary logistic regression results emphasized the relative importance of age, education, medical preference and policy knowledge on the willingness to sign up. Distrust of family doctors’ medical skills (65.7%), not knowing how to contract (47.8%), and not knowing what medical problems can be solved (41.1%) were the top three reasons accounting for the reluctance of residents to contract with family doctors. Conclusion Residents from different backgrounds have different willingness to sign up, so the specific circumstances and needs of different groups should be taken into account. In order to increase the signing-up rate, consideration can be given to promoting the family doctor model in Fujian throughout the country. Individual hesitation can be eliminated by increasing the reimbursement rate of health insurance, reducing the out-of-pocket expenses of contracted patients, and providing incentives of certain discounts for consecutive contracted patients.

Abstract Background Coix seed extract (CSE), a traditional Chinese medicine, has been reported as an adjunctive therapy in cancers. However, the molecular targets are largely unclear. The study is designed to unveil its function in lung adenocarcinoma (LUAD) and the possible molecular mechanism. Methods The HERB database was utilized to predict the molecular targets of the Coix seed, followed by prognostic value prediction in the Kaplan–Meier Plotter database. LUAD cells were infected with sh-KCTD9 after co-culture with CSE, and cell viability, growth, proliferation, and apoptosis were determined. The substrates of KCTD9 were predicted using a protein–protein interaction network and verified. The expression of PD-L1, the contents of TNF-α, IFN-γ, CXCL10, and CXCL9 in the co-culture system of LUAD cells and T cells and the proliferation of T cells were evaluated to study the immune escape of LUAD cells in response to CSE and sh-KCTD9. Lastly, tumor growth and immune escape were observed in tumor-bearing mice. Results CSE inhibited malignant behavior and immune escape of LUAD cells, and the reduction of KCTD9 reversed the inhibitory effect of CSE on malignant behavior and immune escape of LUAD cells. Knockdown of KCTD9 expression inhibited ubiquitination modification of TOP2A, and knockdown of TOP2A suppressed immune escape of LUAD cells in the presence of knockdown of KCTD9. CSE exerted anticancer effects in mice, but the reduction of KCTD9 partially compromised the anticancer effect of CSE. Conclusion CSE inhibits immune escape and malignant progression of LUAD through KCTD9-mediated ubiquitination modification of TOP2A.

Abstract Objective The primary object of this study is to analyze chromosomal abnormalities in miscarriages detected by copy number variants sequencing (CNV-Seq), establish potential pathways or genes related to miscarriages, and provide guidance for birth health in the following pregnancies. Methods This study enrolled 580 miscarriage cases with paired clinical information and chromosomal detection results analyzed by CNV-Seq. Further bioinformatic analyses were performed on validated pathogenic CNVs (pCNVs). Results Of 580 miscarriage cases, three were excluded as maternal cell contamination, 357 cases showed abnormal chromosomal results, and the remaining 220 were normal, with a positive detection rate of 61.87% (357/577). In the 357 miscarriage cases, 470 variants were discovered, of which 65.32% (307/470) were pathogenic. Among all variants detected, 251 were numerical chromosomal abnormalities, and 219 were structural abnormalities. With advanced maternal age, the proportion of numerical abnormalities increased, but the proportion of structural abnormalities decreased. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis revealed that eleven pathways and 636 biological processes were enriched in pCNVs region genes. Protein–protein interaction analysis of 226 dosage-sensitive genes showed that TP53, CTNNB1, UBE3A, EP300, SOX2, ATM, and MECP2 might be significant in the development of miscarriages. Conclusion Our study provides evidence that chromosomal abnormalities contribute to miscarriages, and emphasizes the significance of microdeletions or duplications in causing miscarriages apart from numerical abnormalities. Essential genes found in pCNVs regions may account for miscarriages which need further validation.

The carbon emissions arising from road pavement infrastructures have emerged as critical issue in recent years. The life cycle of a pavement can be divided into five phases, namely raw materials and production, construction, use, maintenance and end of life. While the use phase generates the highest carbon emissions throughout the pavement's life cycle, it is usually neglected in most pavement life cycle assessment (LCA) studies due to its complexity and uncertainty. Therefore, this review selected 126 relevant references, focuses on quantification methods, influential factors and reduction technologies of carbon emissions in pavement use phase. Among the carbon accounting approached, the LCA approach, remains the most widely used for evaluating the environmental impact of pavements. Second, the primary influential factors on the use phase' carbon emission include pavement-vehicle interaction primarily affected by pavement roughness, pavement albedo and climate change. Most influential factors above indirectly cause changes in carbon emissions by influencing the pavement performance and subsequent vehicle emissions. Finally, the review surveys carbon emission reduction technologies during pavement use phase, focusing mainly on reducing pavement rolling resistance and constructing cool pavements. Reflective pavements and permeable pavements are the most widely used cool pavement technologies. Overall, the aspects involved in this paper hold significant promise for quantifying and reducing carbon emissions in the pavement use phase.

Background: The Klebsiella oxytoca complex is an opportunistic pathogen that has been recently identified as an actual complex. However, the characteristics of each species remain largely unknown. We aimed to study the clinical prevalence, antimicrobial profiles, genetic differences, and interaction with the host of each species of this complex. Methods: One hundred and three clinical isolates of the K. oxytoca complex were collected from 33 hospitals belonging to 19 areas in China from 2020 to 2021. Species were identified using whole genome sequencing based on average nucleotide identity. Clinical infection characteristics of the species were analyzed. Comparative genomics and pan-genome analyses were performed on these isolates and an augmented dataset, including 622 assemblies from the National Center for Biotechnology Information. In vitro assays evaluating the adhesion ability of human respiratory epithelial cells and survivability against macrophages were performed on randomly selected isolates. Results: Klebsiella michiganensis (46.6%, 48/103) and K. oxytoca (35.92%, 37/103) were the major species of the complex causing human infections. K. michiganensis had a higher genomic diversity and larger pan-genome size than did K. oxytoca. K. michiganensis isolates with blaoxy-5 had a higher resistance rate to various antibiotics, antimicrobial gene carriage rate, adhesion ability to human respiratory epithelial cells, and survival rate against macrophages than isolates of other species. Conclusion: Our study revealed the genetic diversity of K. michiganensis and firstly identified the highly antimicrobial-resistant profile of K. michiganensis carrying blaoxy-5.

Background With the development of spinal endoscopic techniques, on the basis of our previous experience in treating various types of cervical disc herniation with this endoscopic technique, we took the lead in applying the percutaneous fully endoscopic anterior transcorporeal procedure to be utilized in the treatment of the isolated cervical ossification of the posterior longitudinal ligament (OPLL). Case Presentation A 66‐year‐old male patient who weighed 57 kg, with a height of 169 cm was admitted to the hospital on September 16, 2021 because of recurrent pain and numbness in the neck, shoulder, and right arm for 2 years, which as aggravated for the last 2 weeks. Two years ago, the patient developed neck and shoulder pain accompanied by right arm pain without obvious predisposing factors, and numbness in the first web space of the right hand. In the last 2 weeks, he had difficulty moving the right arm, but no pain or numbness in the contralateral arm. MRI and CT scans demonstrated that the ossified posterior longitudinal ligament of the cervical 5/6 vertebrae with spinal canal stenosis and seriously compressed the spinal cord patient was treated with a percutaneous fully endoscopic anterior transcorporeal procedure. Conclusion Our percutaneous fully endoscopic anterior transcorporeal procedure is a feasible, minimally invasive surgery for treating isolated ossification of the posterior longitudinal ligament in the cervical spine.

AIM: To describe the clinical, electrophysiological, and genetic features of an unusual case with an RDH12 homozygous pathogenic variant and reviewed the characteristics of the patients reported with the same variant. METHODS: The patient underwent a complete ophthalmologic examination including best-corrected visual acuity, anterior segment and dilated fundus, visual field, spectral-domain optical coherence tomography (OCT) and electroretinogram (ERG). The retinal disease panel genes were sequenced through chip capture high-throughput sequencing and Sanger sequencing was used to confirm the result. Then we reviewed the characteristics of the patients reported with the same variant. RESULTS: A 30-year male presented with severe early retinal degeneration who complained night blindness, decreased visual acuity, vitreous floaters and amaurosis fugax. The best corrected vision was 0.04 OD and 0.12 OS, respectively. The fundus photo and OCT showed bilateral macular atrophy but larger areas of macular atrophy in the left eye. Autofluorescence shows bilateral symmetrical hypo-autofluorescence. ERG revealed that the amplitudes of a- and b-wave were severely decreased. Multifocal ERG showed decreased amplitudes in the local macular area. A homozygous missense variant c.146C>T (chr14:68191267) was found. The clinical characteristics of a total of 13 patients reported with the same pathologic variant varied. CONCLUSION: An unusual patient with a homozygous pathogenic variant in the c.146C>T of RDH12 which causes late-onset and asymmetric retinal degeneration are reported. The clinical manifestations of the patient with multimodal retinal imaging and functional examinations have enriched our understanding of this disease.

In this study, a trisodium citrate (TSC)-assisted hydrothermal method is utilized to prepare three-dimensional hydroxyapatite (3D HA). Understanding the role of TSC in the preparation of 3D HA crystals may provide valuable methods to design advanced biomaterials. As one of the indexes of solution supersaturation, the initial pH (ipH) value can not only directly affect the nucleation rate, but also affect the growth of HA crystals. In this work, the effect of the ipH on the microstructure, particle size distribution, and specific surface area of the 3D HA is explored. Results showed that the morphology of 3D HA transformed from a bundle to a dumbbell ball and then a dumbbell with an increase in the ipH. A corresponding mechanism of such a structural evolution was proposed, providing inspiration for the fabrication of innovative 3D HA structures with enhanced biological functionality and performance.

ABSTRACT The emergence of carbapenem-resistant Escherichia coli strains poses a considerable challenge to global public health, and little is known about carbapenemase-producing E. coli strains in Tianjin, China. This study aimed to investigate the risk factors for infections with carbapenem-resistant E. coli (CREC) strains. This retrospective case–control study was conducted at a tertiary teaching hospital. A total of 134 CREC clinical isolates were collected from the General Hospital of Tianjin Medical University between 2013 and 2020. The control group was selected at a ratio of 1:1 from patients with nosocomial carbapenem-susceptible E. coli infection. Risk factors for nosocomial CREC infection and clinical outcomes were analyzed using univariate and multivariate analyses. Multivariate analysis revealed that cephalosporin exposure (odd ratio OR = 2.01), carbapenem exposure (OR = 1.96), glucocorticoid exposure (OR = 32.45), and surgical history (OR = 3.26) were independent risk factors for CREC infection. The in-hospital mortality rate in the CREC group was 29.1%, and age >65 years (OR = 3.19), carbapenem exposure (OR = 3.54), and central venous catheter insertion (OR = 4.19) were independent risk factors for in-hospital mortality in patients with CREC infections. Several factors were identified in the development of nosocomial CREC infections. The CREC isolates were resistant to most antibiotics. Reducing CREC mortality requires a comprehensive consideration of appropriate antibiotic use, underlying diseases, and invasive procedures.IMPORTANCEEscherichia coli is an opportunistic pathogen that causes severe hospital-acquired infections. The spread of carbapenem-resistant E. coli is a global threat to public health, and only a few antibiotics are effective against these infections. Consequently, these infections are usually associated with poor prognosis and high mortality. Therefore, understanding the risk factors associated with the causes and outcomes of these infections is crucial to reduce their incidence and initiate appropriate therapies. In our study, several factors were found to be involved in nosocomial carbapenem-resistant E. coli (CREC) infections, and CREC isolates were resistant to most antibiotics. Reducing CREC mortality needs a comprehensive consideration of whether antibiotics are used appropriately, underlying diseases, and invasive interventions. These findings provide valuable evidence for the development of anti-infective therapy, infection prevention, and control of CREC-positive infections.

Summary: Time-restricted eating (TRE) is a promising obesity management strategy, but weight-loss efficacy varies among participants, and the underlying mechanism is unclear. The study aimed to investigate the role of gut microbiota in weight-loss response during long-term TRE intervention. We analyzed data from 51 obese adults in a 12-month TRE program, categorizing them into distinct weight loss groups (DG) and moderate weight loss groups (MG) based on their TRE responses. Shotgun metagenomic sequencing analysis revealed a significant increase in species closely associated with weight loss effectiveness and metabolic parameter changes in the DG group. Pathways related to fatty acid biosynthesis, glycogen biosynthesis, and nucleotide metabolism were reduced in the DG group and enhanced in the MG group. Next, we identified nine specific species at baseline that contributed better responses to TRE intervention and significant weight loss. Collectively, gut microbiota contributes to responsiveness heterogeneity in TRE and can predict weight-loss effectiveness.

The usage of electromagnetic sources for the improvement of the heat transfer of ferrofluid is an efficient method in heat exchangers. In this article, the effects of the non-uniform electromagnetic field on the thermal characteristics of the nanofluid with 4 % nanoparticles of Fe3O4 streaming inside the pipe with a double cross barrier are extensively investigated. To simulate the nanofluid flow, Computational Fluid Dynamic is applied and a three-dimensional model is chosen to reveal the main effects of the electromagnetic field on the thermal efficiency of the nanofluid flow. The main novelty of this work is related to the application of the cross baffle and non-uniform magnetic field for the heat transfer improvements. The achieved results show that the existence of the electromagnetic field and cross barrier facilitates the production of the vortex inside the pipe. Therefore, the thermal layer diffusion into the stream more efficiently, and the thermal efficiency of nanofluid is improved. The influence of magnetic field intensity also shows that increasing the thermal efficiency is a direct function of magnetic source intensity.

Summary: In scenarios involving the treatment of complex or coexisting diseases with multiple drugs, the potential for severe adverse drug reactions in patients necessitates the identification of potential drug-drug interactions (DDIs). Most existing computational methods have not taken into account the asymmetry and relation types of drug interactions caused by the relation information between drugs, which may lead to missing information in embedded learning. Therefore, this paper proposes a directed relation graph attention aware network (DRGATAN) to predict asymmetric drug interactions. DRGATAN leverages an encoder to learn multi-relational role embeddings of drugs across different types of relations. The experimental results show that DRGATAN’s performance is superior to recognized advanced methods. The visualization demonstrates the effect of utilizing asymmetric information, and the case analysis validates the reliability of the proposed method. This study provides guidance for predicting asymmetric drug interactions.

Postoperative pulmonary complications (PPCs) are associated with high mortality rates after lung cancer surgery. Although some studies have discussed the different risk factors for PPCs, the relationship between these factors and their impact on PPCs remains unclear. Hence, this study aimed to systematically summarize the incidence and determine the risk factors for PPCs.We conducted a systematic search of five English and four Chinese databases from their inception to April 1, 2023. A total of 34 articles (8 cohort studies and 26 case-control studies) (n = 31696, 5833 with PPCs) were included in the analysis. The primary outcome was the incidence of PPC. The secondary outcome was the odds ratio (OR) of PPCs based on the identified risk factors calculated by RevMan 5.4. A narrative descriptive summary of the study results was presented when pooling the results or conducting a meta-analysis was not possible.The pooled incidence of PPCs was 18.4 %. This meta-analysis demonstrated that TNM staging (OR 4.29, 95 % CI 2.59–7.13), chronic obstructive pulmonary disease (COPD) (OR 2.47, 95 % CI 1.80–3.40), smoking history (OR 2.37, 95 % CI 1.33–4.21), poor compliance with respiratory rehabilitation (OR 1.64, 95 % CI 1.17–2.30), male sex (OR 1.62, 95 % CI 1.28–2.04), diabetes (OR 1.56, 95 % CI 1.07–2.27), intraoperative bleeding volume (OR 1.44, 95 % CI 1.02–2.04), Eastern Cooperative Oncology Group score (ECOG) > 1 (OR 1.37, 95 % CI 1.04–1.80), history of chemotherapy and/or radiotherapy (OR 1.32, 95 % CI 1.03–1.70), older age (OR 1.18, 95 % CI 1.11–1.24), and duration of surgery (OR 1.07, 95 % CI 1.04–1.10) were significantly associated with a higher risk of PPCs. In contrast, the peak expiratory flow rate (PEF) (OR 0.99, 95 % CI 0.98–0.99) was a protective factor. Clinicians should implement targeted and effective interventions to prevent the occurrence of PPCs.

Malolactic fermentation (MLF) is a crucial process to enhance wine quality, and the utilization of indigenous microorganisms has the potential to enhance wine characteristics distinct to a region. Here, the MLF performance of five indigenous Oenococcus oeni strains and six synthetic microbial communities (SynComs), were comparatively evaluated in Cabernet Sauvignon wine. In terms of malate metabolism rate and wine aroma diversity, the strain of O. oeni Oe114–46 demonstrated comparable MLF performance to the commercial strain of O. oeni Oe450 PreAc. Furthermore, the corresponding SynComs (Oe144–46/LpXJ25) exhibited improved fermentation properties, leading to increased viable cell counts of both species, more rapid and thorough MLF, and increased concentrations of important aroma compounds, such as linalool, 4-terpinenol, α-terpineol, diethyl succinate, and ethyl lactate. These findings highlight the remarkable MLF performance of indigenous O. oeni and O. oeni-L. plantarum microbial communities, emphasizing their immense potential in improving MLF efficiency and wine quality.

BackgroundMalignant mesothelioma (MM) is a rare and aggressive tumor that is found in the pleura and peritoneum. A few cases of MM in the pericardium and tunica vaginalis testis have been reported. Moreover, primary occurrence in the atrium is extremely rare. The visual appearance of this tumor is similar to that of a common atrial myxoma, which makes it challenging for clinicians and radiologists to diagnose and treat this disease.Case demonstrationAn 18-year-old woman presented with symptoms of chest pain, shortness of breath, cough, and expectoration for 7 days. Echocardiography was performed on the patient, which revealed an atrial mass. Myxoma was one of the differential diagnoses. The tumor was an elliptical mass with tips, and the cut surface was jelly-like, similar to myxoma. After surgery, a pathologic examination of the biopsied tumor confirmed epithelial-type MM. During postoperative follow-up, no recurrence of the tumor was observed.ConclusionsMM originating in the atrium is considered to be extremely rare. Consequently, clinicians can easily misdiagnose atrial MM as a myxoma. Moreover, to confirm the diagnosis, histopathologic biopsy, histomorphological characterization, immunohistochemistry, and molecular genetic testing are required. Therefore, clinical diagnosis and treatment of MM are challenging.