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Abstract To study the degradation of lncRNAs in EPMI in rat brain tissue, this study provides a new direction for the estimation of EPMI. LncRNA high-throughput sequencing was performed on the brain tissues of hemorrhagic shock model rats at 0 h and 24 h, and the target lncRNAs were screened. Samples at 0, 1, 3, 6, 12, 18 and 24 h after death were collected, and miRNA-9 and miRNA-125b were used as reference genes. The relative expression levels of lncRNAs at each PMI were detected by RT–qPCR, and a functional model involving lncRNAs and EPMI was established. Samples were collected at 6, 9, 15, and 21 h after death for functional model verification. The expression of several lncRNAs decreased with the prolongation of EPMI, and the mathematical model established by several lncRNA indices exhibited good fit. The verification results of the multi-index joint function model are significantly better than those of the single-index function model, and the established model is more practical. There is a linear relationship between lncRNAs and EPMI, and the multi-index function model is significantly better than the single-index function model, which is important for EPMI inference in forensic pathology practice.

Abstract Effective management of natural resources is crucial for diminishing carbon emissions. This research explores how economic, financial, and political risks influence the relationship between natural resources rents and carbon emissions. Analyzing data from 66 countries, this study utilizes methods such as quantile regression and dynamic threshold regression to thoroughly assess the data. The findings reveal: (i) Natural resources rents tend to increase carbon emissions consistently across different quantiles (0.1 to 0.9). The fact is confirmed by robustness checks, illustrating that increased natural resources rents lead to higher emissions. (ii) Economic, financial, and political risks affect how natural resources rents impact carbon emissions. Notably, reduced economic and financial risks lessen the propensity of natural resources rents to boost emissions at higher quantiles, while a decline in political risk decreases the exacerbating effect of natural resources rents on emissions from the 0.1 to 0.9 quantiles. (iii) This analysis uncovers threshold effects where economic, financial, and political risks act as threshold factors. Specifically, when economic and political risks are low, a rise in natural resources rents actually leads to a decline in carbon emissions. The findings underscore the importance of considering these risks in the formulation of policies aimed at reducing carbon emissions from natural resource exploitation.

Abstract The implementation of the Gob-Side Entry Retaining Mining Mode with Roof Cutting and Pressure Relief (GERRCPR) results in the gob connecting to the retaining roadway, creating an open space that causes significant air leakage and increases the risk of spontaneous combustion. A study was conducted during the implementation of the GERRCPR in the Xiaonan Coal Mine N1-1502 working face to investigate spontaneous combustion characteristics, along with fire prevention and extinguishing measures. To analyze gob airflow, Computational Fluid Dynamics (CFD) was employed to collect data on airflow conditions, O2 concentration, and temperature. Based on this, this study focuses on exploring the effects of nitrogen injection treatment under various rates and positions to optimize parameters for buried pipe nitrogen injection. Results indicated that within the GERRCPR, air leakage in the gob increased, leading to an increase in O2 concentration, expansion of the oxidation zone, and an elevated risk of spontaneous combustion. Air leakage primarily occurred from the retaining roadway and the working face near the intake-air roadway, peaking at a retaining roadway length of 500 m, with a flow rate of 226 m3/min. Following nitrogen injection treatment, the oxidation zone was significantly reduced, with optimal treatment achieved at a nitrogen injection depth of 70 m and a rate of 600 m3/h. Field monitoring data showed that the inertization measure of using porous long pipes, a nitrogen injection spacing of 30 m, and a nitrogen injection rate of 600 m3/h significantly decreased the O2 concentration within the gob. This reduction meets safety production requirements and outperforms the effectiveness of traditional buried-pipe nitrogen injection methods, thereby validating the simulation accuracy. Understanding the laws governing spontaneous coal combustion in the GERRCPR and enacting preventive measures for nitrogen injection can improve safety standards in mining operations. This proactive approach can effectively prevent spontaneous coal combustion accidents, resulting in substantial social benefits.

Abstract Feline mesenchymal stem cells (fMSCs) are well known for their robust differentiation capabilities and are commonly used in studying immune-related diseases in cats. Despite their importance, the susceptibility of fMSCs to viral infections remains uncertain. This study aimed to assess the susceptibility of feline adipose-derived mesenchymal stem cells (fAD-MSCs) and feline umbilical cord-derived mesenchymal stem cells (fUC-MSCs) to common feline viruses, including feline coronavirus (FCoV), feline herpesvirus type 1 (FHV-1), and feline panleukopenia virus (FPV). The results demonstrated that both FCoV and FHV-1 were able to infect both types of cells, while FPV did not exhibit cytopathic effects on fUC-MSCs. Furthermore, all three viruses were successfully isolated from fAD-MSCs. These findings suggest that certain feline viruses can replicate in fMSCs, indicating potential limitations in using fMSCs for treating viral diseases caused by these specific viruses. This study has important clinical implications for veterinarians, particularly in the management of viral diseases.

Abstract The application of terahertz time-domain spectroscopy (THz-TDS) in the quantitative analysis of major minerals in Bayan Obo magnetite ore was explored. The positive correlation between the optical parameters of the original ore and its iron content is confirmed. The detections of three main iron containing minerals, including magnetite, pyrite, and hematite, were simulated using corresponding reagents. The random forest algorithm is used for quantitative analysis, and FeS2 is detected with precision of R2 = 0.7686 and MAE = 0.6307% in ternary mixtures. The experimental results demonstrate that THz-TDS can distinguish specific iron containing minerals and reveal the potential application value of this testing method in exploration and mineral processing fields.

Abstract We aim to explore the alterations of objective ocular torsion after unilateral lateral rectus recession-medial rectus resection (R&R) for intermittent exotropia (IXT). Seventy-two IXT patients undergoing R&R between March and June 2023 were enrolled. Ophthalmological examinations were performed before surgery and at 1 week and 1 month after surgery, mainly including prism and alternate cover test and optical coherence tomography. The mean disc-foveal angle of eyes showing intorsion significantly increased from − 1.5 ± 0.9° preoperatively to 2.0 ± 2.0° at 1 week (P = 0.0227) and 2.2 ± 1.6° at 1 month postoperatively (P = 0.0054). The mean disc-foveal angle of eyes exhibiting extorsion significantly reduced from 12.8 ± 1.9° preoperatively to 9.8 ± 3.1° at 1 week (P

Abstract In flowering plants, the predominant sexual morph is hermaphroditism, and the emergence of unisexuality is poorly understood. Using Cucumis melo (melon) as a model system, we explore the mechanisms driving sexual forms. We identify a spontaneous mutant exhibiting a transition from bisexual to unisexual male flower, and identify the causal mutation as a Harbinger transposon impairing the expression of Ethylene Insensitive 2 (CmEIN2) gene. Genetics and transcriptomic analysis reveal a dual role of CmEIN2 in both sex determination and fruit shape formation. Upon expression of CmACS11, EIN2 is recruited to repress the expression of the carpel inhibitor, CmWIP1. Subsequently, EIN2 is recruited to mediate stamina inhibition. Following the sex determination phase, EIN2 promotes fruit shape elongation. Genome-wide analysis reveals that Harbinger transposon mobilization is triggered by environmental cues, and integrates preferentially in active chromatin, particularly within promoter regions. Characterization of a large collection of melon germplasm points to active transpositions in the wild, compared to cultivated accessions. Our study underscores the association between chromatin dynamics and the temporal aspects of mobile genetic element insertions, providing valuable insights into plant adaptation and crop genome evolution.

Addressing peripheral nerve defects remains a significant challenge in regenerative neurobiology. Autografts emerged as the gold-standard management, however, are hindered by limited availability and potential neuroma formation. Numerous recent studies report the potential of wireless electronic system for nerve defects repair. Unfortunately, few has met clinical needs for inadequate electrode precision, poor nerve entrapment and insufficient bioactivity of the matrix material. Herein, we present an advanced wireless electrical nerve stimulator, based on water-responsive self-curling silk membrane with excellent bioabsorbable and biocompatible properties. We constructed a unique bilayer structure with an oriented pre-stretched inner layer and a general silk membrane as outer layer. After wetting, the simultaneous contraction of inner layer and expansion of outer layer achieved controllable super-contraction from 2D flat surface to 3D structural reconfiguration. It enables shape-adaptive wrapping to cover around nerves, overcomes the technical obstacle of preparing electrodes on the inner wall of the conduit, and prevents electrode breakage caused by material expansion in water. The use of fork capacitor-like metal interface increases the contact points between the metal and the regenerating nerve, solving the challenge of inefficient and rough electrical stimulation methods in the past. Newly developed electronic stimulator is effective in restoring 10 mm rat sciatic nerve defects comparable to autologous grafts. The underlying mechanism involves that electric stimulation enhances anterograde mitochondrial transport to match energy demands. This newly introduced device thereby demonstrated the potential as a viable and efficacious alternative to autografts for enhancing peripheral nerve repair and functional recovery.

Abstract The association of cardio‐ankle vascular index (CAVI), with subclinical cardiac dysfunction in hypertensive patients is unclear. We aim to examine their relationship in hypertensive patients compared with that in normotensive subjects. Our study included 1887 subjects enrolled from Danyang between 2018 and 2019. CAVI was measured using VaSera VS‐1500A device. We performed conventional echocardiography to measure ejection fraction (EF) and E/A, tissue Doppler to measure mitral annular early diastolic velocities (e’), and speckle‐tracking to estimate left ventricular (LV) global longitudinal strain (GLS). LV mass index (76.3, 80.0, and 84.0 g/m2), and E/e’ (7.6, 8.2, and 8.8) were increased and GLS (21.1, 21.0, and 20.4%), E/A (1.2, 1.0, and 0.8) and e’ velocity (11.2, 9.4, and 8.2 cm/s) was decreased from tertiles 1–3 of CAVI on unadjusted analyses (P

Abstract Background Patients with cold tumors gain limited benefits from immune checkpoint blockade (ICB) therapy owing to low programmed cell death protein ligand 1 (PD‐L1) expression and minimal immune cell infiltration. Mild photothermal therapy (PTT) using black phosphorus nanosheets (BPNSs) is a promising approach to enhance the efficacy of ICB therapy. However, to ensure that BPNS‐based PTT‐enhanced ICB therapy is clinically adaptable, a noninvasive, bedside‐accessible imaging tool capable of monitoring the status of PD‐L1 is imperative. We demonstrated that positron emission tomography (PET) using [64Cu]HKP2202 precisely delineated PD‐L1 expression in tumors receiving PTT. Methods BPNSs were modified with polyethylene glycol to prepare BPNS@PEG, which were then characterized. MC38 cells and tumor allografts were treated with BPNS@PEG followed by 808 nm near‐infrared light exposure. PET using [64Cu]HKP2202 was performed to monitor PD‐L1 expression in vivo. We also evaluated whether the efficacy of ICB therapy improved after delivering BPNS@PEG‐based PTT. Results BPNS@PEG had a well‐defined lamellar structure with clear edges and an average size of 150 nm. PET and Western blotting assays indicated that PD‐L1 expression was upregulated after BPNS@PEG and NIR‐light treatment. Notably, the antitumor effect of anti PD‐L1 therapy was enhanced in mice treated with BPNS@PEG‐based PTT. Conclusions BPNS@PEG had the capacity to convert cold tumors into hot tumors to facilitate the efficacy of ICB therapy. Importantly, the complementary diagnostic PET radiotracer targeting PD‐L1 allowed real‐time monitoring of PD‐L1 expression in the tumor microenvironment to guide ICB administration, holding great potential to achieve efficient and precise tumor immunotherapy.

Abstract The importance of P-stereogenic heterocycles has been widely recognized with their extensive use as privileged chiral ligands and bioactive compounds. The catalytic asymmetric synthesis of P-stereogenic phosphindane derivatives, however, remains a challenging task. Herein, we report a catalytic kinetic resolution of phosphindole oxides via rhodium-catalyzed diastereo- and enantioselective conjugate addition to access enantiopure P-stereogenic phosphindane and phosphindole derivatives. This kinetic resolution method features high efficiency (s factor up to >1057), excellent stereoselectivities (all >20:1 dr, up to >99% ee), and a broad substrate scope. The obtained chiral phosphindane oxides exhibit promising therapeutic efficacy in autosomal dominant polycystic kidney disease (ADPKD), and compound 3az is found to significantly inhibit renal cyst growth both in vitro and in vivo, thus ushering in a promising scaffold for ADPKD drug discovery. This study will not only advance efforts towards the asymmetric synthesis of challenging P-stereogenic heterocycles, but also surely inspire further development of P-stereogenic entities for bioactive small-molecule discovery.

Abstract Objectives Focal cortical dysplasia (FCD) represents one of the most common causes of refractory epilepsy in children. Deep learning demonstrates great power in tissue discrimination by analyzing MRI data. A prediction model was built and verified using 3D full-resolution nnU-Net for automatic lesion detection and segmentation of children with FCD II. Methods High-resolution brain MRI structure data from 65 patients, confirmed with FCD II by pathology, were retrospectively studied. Experienced neuroradiologists segmented and labeled the lesions as the ground truth. Also, we used 3D full-resolution nnU-Net to segment lesions automatically, generating detection maps. The algorithm was trained using fivefold cross-validation, with data partitioned into training (N = 200) and testing (N = 15). To evaluate performance, detection maps were compared to expert manual labels. The Dice-Sørensen coefficient (DSC) and sensitivity were used to assess the algorithm performance. Results The 3D nnU-Net showed a good performance for FCD lesion detection at the voxel level, with a sensitivity of 0.73. The best segmentation model achieved a mean DSC score of 0.57 on the testing dataset. Conclusion This pilot study confirmed that 3D full-resolution nnU-Net can automatically segment FCD lesions with reliable outcomes. This provides a novel approach to FCD lesion detection. Critical relevance statement Our fully automatic models could process the 3D T1-MPRAGE data and segment FCD II lesions with reliable outcomes. Key points • Simplified image processing promotes the DL model implemented in clinical practice. • The histopathological confirmed lesion masks enhance the clinical credibility of the AI model. • The voxel-level evaluation metrics benefit lesion detection and clinical decisions. Graphical Abstract

The role of the gut microbiota in host physiology has been previously elucidated for some marine organisms, but little information is available on their metabolic activity involved in transformation of environmental pollutants. This study assessed the metabolic profiles of the gut microbial cultures from grouper (Epinephelus coioides), green mussel (Perna viridis) and giant tiger prawn (Penaeus monodon) and investigated their transformation mechanisms to typical plastic additives. Community-level physiological profiling analysis confirmed the utilization profiles of the microbial cultures including carbon sources of carbohydrates, amines, carboxylic acids, phenolic compounds, polymers and amino acids, and the plastic additives of organophosphate flame retardants, tetrabromobisphenol A derivates and bisphenols. Using in vitro incubation, triphenyl phosphate (TPHP) was found to be rapidly metabolized into diphenyl phosphate by the gut microbiota as a representative ester-containing plastic additive, whereas the transformation of BPA (a representative phenol) was relatively slower. Interestingly, all three kinds of microbial cultures efficiently transformed the hepatic metabolite of BPA (BPA-G) back to BPA, thereby increasing its bioavailability in the body. The specific enzyme analysis confirmed the ability of the gut microbiota to perform the metabolic reactions. The results of 16S rRNA sequencing and network analysis revealed that the genera Escherichia-Shigella, Citrobacter, and Anaerospora were functional microbes, and their collaboration with fermentative microbes played pivotal roles in the transformation of the plastic additives. The structure-specific transformations by the gut microbiota and their distinct bioavailability deserve more attention in the future.

Hepatocellular carcinoma (HCC) presents a significant global health challenge, necessitating the exploration of novel chemical entities or innovative therapeutic approaches targeting diverse signaling mechanisms. In this study, our focus was on developing a series of ureido/thioureido derivatives with a 4-phenylthiazol-2-amine scaffold to design structurally innovative candidates for HCC treatment, drawing inspiration from the structural characteristics of type II inhibitors like Sorafenib. The synthesized compounds underwent comprehensive evaluation for their antiproliferative activities against human MCF7, HepG2, QGY7703, SMMC-7721, Huh-7, and PLC cells. Additionally, investigations into the molecular targets of selected compounds were conducted. Notably, compound 31 emerged as a standout performer, displaying an IC50 of 0.94 ± 0.29 μM against HepG2 cells, surpassing the efficacy of Sorafenib (1.62 ± 0.27 μM). Further investigations revealed its capability for G2/M phase arrest, apoptosis induction, and significant inhibition of cell cloning and migration in HepG2 cells. Moreover, compound 31 exhibited a notable positive effect on IGF1R, with a significant inhibitory activity of 69.22 % at a concentration of 10 μM. Molecular docking analyses revealed a stronger affinity between compound 31 and the receptor compared to the IGF1R inhibitor OZN2290. In conclusion, compound 31 emerges as a promising candidate for HCC treatment.

The evaluation of well integrity in double-casing wells is critical for ensuring well stability, preventing oil and gas leaks, avoiding pollution, and ensuring safety throughout well development and production. However, the current predominant method of assessing cementing quality primarily focuses on single-casing wells, with limited work conducted on double-casing wells. This study introduces a novel approach for evaluating the cementing quality using the Inception module of convolutional neural networks. First, the finite-difference method is employed to generate borehole sonic data corresponding to a variety of model configurations, which are used to train a neural network that learns spatial features from the borehole sonic data to reconstruct the slowness model. By adjusting the network architecture and parameters, it is discovered that a neural network with two blocks and 4096 nodes in the fully connected layer demonstrated the best imaging results and exhibited strong anti-noise capabilities. The proposed method is validated using practical wellbore size models, demonstrating excellent results and offering a more effective means of evaluating wellbore integrity in double-casing wells. In addition, dipole acoustic logging data are used to conduct slowness model imaging of the compressional (P-) wave and shear (S-) wave in double-casing wells to verify the feasibility of cementing quality evaluation. The developed method contributes to more accurate evaluations of wellbore integrity for the oil and gas industry, leading to improved safety and environmental outcomes.

Purpose: To investigate the inhibition of myopia progression and axial elongation in children wearing orthokeratology (OK) lenses, as well as to evaluate the status of corneal reshaping, this study explores the relationship between changes in central corneal curvature (K-value) and e-value induced by OK lenses and axial elongation. Methods: In this study, it is planned to select children aged 8–15 who wear orthokeratology lenses at the Pediatric Ophthalmology and Strabismus Clinic of the Second Affiliated Hospital of Dalian Medical University. All children will undergo slit lamp examination, visual acuity assessment, computerized refraction, intraocular pressure measurement, biometry, and corneal topography examination before lens wear and at 1 month, 3 months, and 6 months after lens wear in the pediatric ophthalmology clinic. Based on age (lower age group (8 0.05). There were no significant differences in refractive error among the four groups (P = 0.066, >0.05). Baseline axial length differed significantly among the four groups (P = 0.000, 0.05). Significant differences were observed in corneal flat K-value change compared to baseline among the four groups at 1 month, 3 months, and 6 months (P1 = 0.001, P3 = 0.001, P6 = 0.004, 0.05), but significant differences were found in e-value change compared to baseline at 6 months (P6 = 0.010,

Abstract Atherosclerosis, a chronic disease associated with metabolism, poses a significant risk to human well‐being. Currently, existing treatments for atherosclerosis lack sufficient efficiency, while the utilization of surface‐modified nanoparticles holds the potential to deliver highly effective therapeutic outcomes. These nanoparticles can target and bind to specific receptors that are abnormally over‐expressed in atherosclerotic conditions. This paper reviews recent research (2018–present) advances in various ligand‐modified nanoparticle systems targeting atherosclerosis by specifically targeting signature molecules in the hope of precise treatment at the molecular level and concludes with a discussion of the challenges and prospects in this field. The intention of this review is to inspire novel concepts for the design and advancement of targeted nanomedicines tailored specifically for the treatment of atherosclerosis.

The Yangtze River Basin was among the areas most severely affected by the widespread extreme drought in the Northern Hemisphere in 2022. Drought conditions in this basin extended into the wintering season, significantly influencing waterfowl habitat availability. Exploring how waterfowl distributions and ecological niches respond to these changes in wetland environmental conditions and the underlying ecological mechanisms are important for biodiversity conservation and understanding wetland ecological processes. By integrating field observations, remote sensing, and ecological niche modelling, we analysed habitat changes over the past decade and investigated how extreme drought affected the distribution patterns and spatial niches of two waterfowl guilds, ducks and geese, in the Dongting Lake Region, a key wetland ecosystem in the Yangtze River Basin. The extreme drought led to a drastic reduction in the waterbody area of natural habitats and caused vegetation to enter the wilting stage prematurely. In response, a substantial proportion of waterfowl shifted to adjacent managed wetlands with stable water levels, especially the ducks, whose distribution pattern was fundamentally altered. The proportion of both waterfowl guilds in the managed wetland showed a significant correlation with the proportion of the waterbody area. Further, we compared the spatial niche of waterfowl in 2022 with that in the former year, which represented a typical year with normal hydrology. The spatial niche of ducks underwent a substantial contraction, while that of geese remained large in both years but shifted inward in 2022 towards areas with lower elevation, and foraging resource use was altered. Therefore, for both waterfowl guilds, the extent of habitat overlap between the two years was small. This study has important implications for understanding the impact of extreme climatic and hydrological events on wetland ecosystems. Furthermore, our results emphasise the importance of water level-managed wetlands for biodiversity conservation.

Abstract Background Poor development of young children is a common issue in developing countries and it is well established that iron deficiency anemia is one of the risk factors. Research has shown that iron deficiency is a common micronutrient deficiency among children in rural China and can result in anemia. A previous paper using data from the same trial as those used in the current study, but conducted when sample children were younger, found that after 6 months of providing caregivers of children 6–11 months of age free access to iron-rich micronutrient powder (MNP) increased the hemoglobin concentrations (Hb) of their children. However, no effects were found 12 and 18 months after the intervention. The current study followed up the children four years after the start of the original intervention (when the children were 4–5 years old) and aims to assess the medium-term impacts of the MNP program on the nutritional status of the sample pre-school-aged children, including their levels of Hb, the prevalence of anemia, and the dietary diversity of the diets of the children. Methods At baseline, this study sampled 1,802 children aged 6–11 months in rural Western China. The intervention lasted 18 months. In this medium-term follow-up study that successfully followed 81% (n = 1,464) of children (aged 49–65 months) from the original study population 4 years after the start of the intervention, we used both intention-to-treat (ITT) effect and average treatment on the treated effect (ATT) analyses to assess the medium-term impacts of the MNP distribution program on the nutritional status of sample children. Results The ITT analysis shows that the MNP intervention decreased the prevalence of anemia of young children in the medium run by 8% (4 percentage points, p

Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis. Over the past 20 years, the search for biomarkers for neuromyelitis optica has been ongoing. Here, we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis optica. Research in this area is consistently increasing, with China and the United States leading the way on the number of studies conducted. The Mayo Clinic is a highly reputable institution in the United States, and was identified as the most authoritative institution in this field. Furthermore, Professor Wingerchuk from the Mayo Clinic was the most authoritative expert in this field. Keyword analysis revealed that the terms “neuromyelitis optica” (261 times), “multiple sclerosis” (220 times), “neuromyelitis optica spectrum disorder” (132 times), “aquaporin 4” (99 times), and “optical neuritis” (87 times) were the most frequently used keywords in literature related to this field. Comprehensive analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple sclerosis. Furthermore, aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum disorder. Myelin oligodendrocyte glycoprotein-IgG is a diagnostic biomarker for myelin oligodendrocyte glycoprotein antibody-associated disease. Recent biomarkers for neuromyelitis optica include cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein, serum astrocyte damage biomarkers like FAM19A5, serum albumin, and gamma-aminobutyric acid. The latest prospective clinical trials are exploring the potential of these biomarkers. Preliminary results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelitis optica spectrum disorder. The ultimate goal of future research is to identify non-invasive biomarkers with high sensitivity, specificity, and safety for the accurate diagnosis of neuromyelitis optica.

Abstract In order to explore the potential application of Ramie fibre (RF) in medical dressing, the absorbency ratio of ramie fibre cloth, medical gauze and natural cotton fibre cloth was tested, and the factors affecting the absorbency ratio of materials were analysed. Meanwhile, the hemocompatibility of the three fibre materials were also studied. The results showed that the RF cloth had good moisture absorption and hemocompatibility. Therefore, RF is a potential material for medical dressing.

Asthma is a chronic inflammatory disease involving structural changes to the respiratory system and severe immune responses mediated by allergic cytokines and pro-inflammatory mediators. Agarum cribrosum (AC) is a kind of seaweed which contains a phlorotannin, trifuhalol A. To evaluate its anti-allergic inflammatory effect against asthma, an ovalbumin inhalation-induced mouse asthma model was used. Histologic observations proved that trifuhalol A is minimizing the lung and tracheal structure changes as well as the infiltration of eosinophils and mast cells against ovalbumin inhalation challenge. From the serum and bronchoalveolar lavage fluid, ovalbumin-specific IgE and Th2-specific cytokines, IL-4, -5, and -13, were reduced with trifuhalol A treatment. In addition, IL-1β, IL-6, and TNF-α concentrations in lung homogenate were also significantly reduced via trifuhalol A treatment. Taken together, trifuhalol A, isolated from AC, was able to protect lung and airways from Th2-specific cytokine release, and IgE mediated allergic inflammation as well as the attenuation of IL-1β, IL-6, and TNF-α in lung, which results in the suppression of eosinophils and the mast cells involved asthmatic pathology.

Abstract The reaction mechanism of the historic copper-catalyzed Glaser coupling has been debated to be based on redox cycles of Cu ions in specific oxidation states or on a radical mechanism based on Cu(0)/Cu(I). Here, the authors demonstrate two coexisting Glaser coupling pathways which can be differentiated by anaerobic/irradiation or aerobic reaction conditions. Without O2, copper(I) acetylides undergo a photo-excited pathway to generate highly reactive alkynyl radicals, which combine together to form a homo-coupling product or individually react with diverse X-H (X = C, N, O, S and P) substrates via hydrogen atom transfer. With O2, copper(I) acetylides are oxidized to become a Cu-acetylide/Cu-O merged Cu(I/II) intermediate for further oxidative coupling. This work not only complements the radical mechanism for Glaser coupling, but also provides a mild way to access highly energetic alkynyl radicals for efficient organic transformations.

Abstract Background Abnormal serum ferritin levels are associated with a variety of diseases. Meanwhile, abnormal serum ferritin is influenced by a variety of risk factors, but its correlation with obesity remains poorly described. Objective This study aimed to investigate the association of body mass index (BMI) and weight waist adjustment index (WWI) with serum ferritin in US adults. Methods Participants in this study took part in the National Health and Nutrition Examination Survey (NHANES) prior to the pandemic from 2017 to March 2020. Serum ferritin was used as the sole response variable and BMI and WWI were used as independent variables. Multiple linear regression was used to assess the relationship between serum ferritin and the independent variables, and smoothed curve fitting and threshold effects analysis were performed to assess the presence of non-linear relationships. To validate the sensitive individuals for the correlation between the independent and the dependent variables, a subgroup analysis was performed. Results A final total of 7552 participants were included in this study. Both independent variables had a positive relationship with serum ferritin, with effect values of (β = 0.68, 95% CI: 0.17–1.19) when BMI was the independent variable and (β = 8.62, 95% CI: 3.53–13.72) when WWI was the independent variable in the fully adjusted model. This positive association between the two obesity-related indexes and serum ferritin became more significant as BMI and WWI increased (P for trend

The Antarctic krill is a pivotal species in the Southern Ocean ecosystem, primarily due to its extraordinary nutritional content and plentiful resources. Studying the distribution of these resources and their environmental impact factors is crucial for the successful development of Antarctic krill fisheries. Traditional methodologies such as acoustic measurements, however, often face limitations in their capacity to provide a comprehensive and uninterrupted assessment. Moreover, the six-month duration of polar nights in polar regions presents significant challenges for traditional satellite observations. In this context, LiDAR, an active remote sensing observation method, offers a promising alternative. Known for their high resolution, flexibility, and efficiency, LiDAR systems can obtain detailed information on diurnal ocean parameters in polar regions on a vast scale and in a systematic way. Our study utilizes the spaceborne LiDAR system, CALIPSO, to successfully attain continuous Antarctic krill CPUE over the past decade, using various models such as the generalized linear model (GLM), artificial neural network (ANN), and support vector machine (SVM). A comparative analysis of the prediction results reveals that while both ANN and SVM models outperform the GLM, the SVM’s prediction capabilities are somewhat unstable. Our findings reveal CALIPSO’s potential in overcoming challenges associated with traditional satellite observations during polar winters. In addition, we found no obvious pattern of interannual variation in krill CPUE, with high values predominantly occurring from February to May. This suggests that krill is mainly located around the South Shetland Islands during January-April, before moving offshore towards South Georgia in May-June. A substantial krill aggregation community is found in the South Atlantic waters, indicating high potential for krill fishing. The optimum mix layer depth range for high krill CPUE is 270-390 m, with a chlorophyll concentration of approximately 0.1 mg m-3. The optimum sea surface temperature range is between -1.4-5.5°C, and the sea ice coverage range is approximately 0-0.1×106 km2. The predicted Antarctic krill bioresource has risen from 2.4×108 tons in 2011 to 2.8×108 tons in 2020. This increase in krill biomass aligns with the biomass of krill assessed by CCAMLR.

This study aimed to determine the effect of prostaglandin F2α (PGF2α) analog (D-cloprostenol sodium and DL-cloprostenol sodium) administration on the milk yield of multiparous sows (MS) and piglet growth performance. In total, 320 Landrace×Yorkshire parturient MS were randomly divided into three groups on day 115 of pregnancy: without treatment (N = 50), with 75 μg D-cloprostenol sodium (N = 137), and with 200 μg DL-cloprostenol sodium (N = 133). After delivery, the sows treated with D-cloprostenol sodium and DL-cloprostenol sodium were randomly allocated into three subgroups, respectively: (i) no additional treatment after farrowing; (ii) administration of cloprostenol sodium at 3 h and 5 days after farrowing; and (iii) administration of cloprostenol sodium at 3 h, 5 days, and 10 days after farrowing. Cloprostenol sodium effectively induced sows to synchronize parturition approximately 23 h after administration and increased the daytime delivery rates (p 0.05). In summary, cloprostenol sodium could enhance the reproductive performance of MS, particularly in terms of lactation performance. Additionally, the effect of quartic injections of D-cloprostenol sodium was the most pronounced.

Background: To provide new ideas for the clinical and mechanism research of acupuncture in the treatment of chronic obstructive pulmonary disease (COPD), this study systematically reviews clinical research and the progress of basic research of acupuncture in the treatment of COPD. Methods: PubMed and Web of Science databases were searched using acupuncture and COPD as keywords in the last 10 years, and the included literature was determined according to exclusion criteria. Findings: Acupuncture can relieve clinical symptoms, improve exercise tolerance, anxiety, and nutritional status, as well as hemorheological changes (blood viscosity), reduce the inflammatory response, and reduce the duration and frequency of COPD in patients with COPD. Mechanistically, acupuncture inhibits M1 macrophage activity, reduces neutrophil infiltration, reduces inflammatory factor production in alveolar type II epithelial cells, inhibits mucus hypersecretion of airway epithelial cells, inhibits the development of chronic inflammation in COPD, and slows tissue structure destruction. Acupuncture may control pulmonary COPD inflammation through the vagal-cholinergic anti-inflammatory, vagal-adrenomedullary-dopamine, vagal-dual-sensory nerve fiber-pulmonary, and CNS-hypothalamus-orexin pathways. Furthermore, acupuncture can increase endogenous cortisol levels by inhibiting the HPA axis, thus improving airway antioxidant capacity and reducing airway inflammation in COPD. In conclusion, the inhibition of the chronic inflammatory response is the key mechanism of acupuncture treatment for COPD.

Objective Our study aims to examine the associations of visceral adipose tissue (VAT) and epicardial adipose tissue (EAT) with subclinical cardiac dysfunction in a Chinese population.Design Cross-sectional.Background EAT and VAT are the most important ectopic fat pools which were previously shown to be associated with subclinical cardiac dysfunction. However, few studies simultaneously measured both EAT thickness and VAT area, and explored their associations with cardiac dysfunction. Our study aims to examine the associations of VAT and EAT with subclinical cardiac dysfunction in a Chinese population.Methods The study subjects were recruited from Danyang County from 2018 to 2019. Using Philips CX50, we recorded EAT thickness at the end-systole in a long-axis view. The subclinical systolic and diastolic function were assessed by two-dimensional speckle tracking, and transmitral and tissue Doppler imaging, respectively. Using Omron HDS-2000, we measured VAT area by dual bioelectrical impedance analysis.Results The 1558 participants (age, 52.3±12.8 years) included 930 (59.7%) women. Compared with women, men had higher VAT area (99.4 vs 70.1 cm2; p

Abstract Organoids are three‐dimensional cell aggregates with near‐physiologic cell behaviors and can undergo long‐term expansion in vitro. They are amenable to high‐throughput drug screening processes, which renders them a viable preclinical model for drug development. The procedure of organoid‐based high‐throughput screening has been extensively employed to discover small‐molecule drugs, encompassing the steps of generating organoids, examining efficient drugs in organoid cultures, and data assessment. Compared to small molecules, peptides are more straightforward to synthesize, can be modified chemically, and demonstrate high target specificity and low cytotoxicity. Therefore, they have emerged as promising carriers to deliver drugs to disease‐associated targets and could be efficient therapeutic drugs for various diseases. To date, organoids have been used to evaluate the efficacy of certain peptide agents; however, no organoid‐based high‐throughput screening of peptide drugs has been reported. Given the advantages of peptide drugs, there is an urgent need to establish organoid‐based peptide high‐throughput screening platforms. In this review, we discuss the typical approach of screening small‐molecular drugs with the use of organoid cultures, as well as provide an overview of the studies that have incorporated organoids in peptide research. Drawing on the knowledge from small molecular screens, we explore the difficulties and potential avenues for creating new platforms to identify peptide agents using organoid models.

Abstract Pancreatic cancer is a highly aggressive cancer, and is primarily treated with gemcitabine, with increasing resistance. SIRT6 as a member of sirtuin family plays important roles in lifespan and diverse diseases, such as cancer, diabetes, inflammation and neurodegenerative diseases. Considering the role of SIRT6 in the cytoprotective effect, it might be a potential anticancer drug target, and is associated with resistance to anticancer therapy. However, very few SIRT6 inhibitors have been reported. Here, we reported the discovery of a pyrrole-pyridinimidazole derivative, 8a, as a new non-competitive SIRT6 inhibitor, and studied its roles and mechanisms in the antitumor activity and sensitization of pancreatic cancer to gemcitabine. Firstly, we found a potent SIRT6 inhibitor compound 8a by virtual screening and identified by molecular and cellular SIRT6 activity assays. 8a could effectively inhibit SIRT6 deacetylation activity with IC50 values of 7.46 ± 0.79 μM in FLUOR DE LYS assay, and 8a significantly increased the acetylation levels of H3 in cells. Then, we found that 8a could inhibit the cell proliferation and induce cell apoptosis in pancreatic cancer cells. We further demonstrate that 8a sensitize pancreatic cancer cells to gemcitabine via reversing the activation of PI3K/AKT/mTOR and ERK signaling pathways induced by gemcitabine and blocking the DNA damage repair pathway. Moreover, combination of 8a and gemcitabine induces cooperative antitumor activity in pancreatic cancer xenograft model in vivo. Overall, we demonstrate that 8a, a novel SIRT6 inhibitor, could be a promising potential drug candidate for pancreatic cancer treatment.

Abstract Objective The comorbidities of coronary artery disease (CAD) and rheumatoid arthritis (RA) are mutual risk factors, which lead to higher mortality, but the biological mechanisms connecting the two remain unclear. Here, we aimed to identify the risk genes for the comorbid presence of these two complex diseases using a network modularization approach, to offer insights into clinical therapy and drug development for these diseases. Method The expression profile data of patients CAD with and without RA were obtained from the GEO database (GSE110008). Based on the differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA) was used to construct a gene network, detect co-expression modules, and explore their relation to clinical traits. The Zsummary index, gene significance (GS), and module membership (MM) were utilized to screen the important differentiated modules and hub genes. The GO and KEGG pathway enrichment analysis were applied to analyze potential mechanisms. Result Based on the 278 DEGs obtained, 41 modules were identified, of which 17 and 24 modules were positively and negatively correlated with the comorbid occurrence of CAD and RA (CAD&RA), respectively. Thirteen modules with Zsummary < 2 were found to be the underlying modules, which may be related to CAD&RA. With GS ≥ 0.5 and MM ≥ 0.8, 49 hub genes were identified, such as ADO, ABCA11P, POT1, ZNF141, GPATCH8, ATF6 and MIA3, etc. The area under the curve values of the representative seven hub genes under the three models (LR, KNN, SVM) were greater than 0.88. Enrichment analysis revealed that the biological functions of the targeted modules were mainly involved in cAMP-dependent protein kinase activity, demethylase activity, regulation of calcium ion import, positive regulation of tyrosine, phosphorylation of STAT protein, and tissue migration, etc. Conclusion Thirteen characteristic modules and 49 susceptibility hub genes were identified, and their corresponding molecular functions may reflect the underlying mechanism of CAD&RA, hence providing insights into the development of clinical therapies against these diseases.

Abstract Biomimetic mechanosensors have profound implications for various areas, including health care, prosthetics, human‒machine interfaces, and robotics. As one of the most important parameters, the sensitivity of mechanosensors is intrinsically determined by the detection resolution to mechanical force. In this manuscript, we expand the force detection resolution of current biomimetic mechanosensors from the micronewton to nanonewton scale. We develop a nanocrack-based electronic whisker-type mechanosensor that has a detection resolution of 72.2 nN. We achieve the perception of subtle mechanical stimuli, such as tiny objects and airflow, and the recognition of surface morphology down to a 30 nm height, which is the finest resolution ever reported in biomimetic mechanosensors. More importantly, we explore the use of this mechanosensor in wearable devices for sensing gravity field orientation with respect to the body, which has not been previously achieved by these types of sensors. We develop a wearable smart system for sensing the body’s posture and movements, which can be used for remote monitoring of falls in elderly people. In summary, the proposed device offers great advantages for not only improving sensing ability but also expanding functions and thus can be used in many fields not currently served by mechanosensors.

Abstract Background The cytotoxicity of NK cells is largely dependent on IgG Fc receptor CD16a, which mediates antibody-dependent cell-mediated cytotoxicity (ADCC). The high-affinity and non-cleavable CD16 (hnCD16) is developed and demonstrated a multi-tumor killing potential. However, the hnCD16 receptor activates a single CD16 signal and provides limited tumor suppression. How to exploit the properties of hnCD16 and incorporate NK cell-specific activation domains is a promising development direction to further improve the anti-tumor activity of NK cells. Methods To expand the applications of hnCD16-mediated ADCC for NK cell-based immunotherapy in cancer, we designed the hnCD16 Fusion Receptor (FR) constructs with the ectodomain of hnCD16 fused with NK cell-specific activating domains in the cytoplasm. FR constructs were transduced into CD16-negative NK cell line and human iPSC-derived NK (iNK) cells and effective FR constructs were screened. The up-regulation of immune activation- and cytokine-releasing-related pathways in FR-transduced NK cells was screened and validated by RNA sequencing and multiplex cytokines release assay, respectively. The tumor-killing efficiency was tested in vitro and in vivo via co-culture with tumor cell lines and xenograft mice-bearing human B-cell lymphoma, respectively. Results We screened the most effective combination to kill B cell lymphoma, which was fused with the ectodomain of hnCD16a, NK-specific co-stimulators (2B4 and DAP10) and CD3ζ in cytoplasmic domains. The screened construct showed excellent cytotoxicity effects and sharp multiple cytokines releasing both in the NK cell line and iNK cells. The transcriptomic analysis and validation assays of hnCD16- and hnCD16FR-transduced NK cells showed that hnCD16FR transduction remodeled immune-related transcriptome in NK cells, where significant upregulation of genes related to cytotoxicity, high cytokines releasing, induced tumor cell apoptosis, and ADCC in comparison with hnCD16 transduction were highlighted. In vivo xenograft studies demonstrated that a single low-dose regimen of engineered hnCD16FR iPSC-derived NK cells co-administered with anti-CD20 mAb treatment mediated potent activity and significantly improved survival. Conclusion We developed a novel hnCD16FR construct that exhibits more potent cytotoxicity than reported hnCD16, which is a promising approach to treat malignancies with improved ADCC properties. We also offer a rationale for NK activation domains that remodel immune response to enhance CD16 signaling in NK cells.

Salinity stress has a great impact on crop growth and productivity and is one of the major factors responsible for crop yield losses. The K-homologous (KH) family proteins play vital roles in regulating plant development and responding to abiotic stress in plants. However, the systematic characterization of the KH family in rice is still lacking. In this study, we performed genome-wide identification and functional analysis of KH family genes and identified a total of 31 KH genes in rice. According to the homologs of KH genes in Arabidopsis thaliana, we constructed a phylogenetic tree with 61 KH genes containing 31 KH genes in Oryza sativa and 30 KH genes in Arabidopsis thaliana and separated them into three major groups. In silico tissue expression analysis showed that the OsKH genes are constitutively expressed. The qRT-PCR results revealed that eight OsKH genes responded strongly to salt stresses, and OsKH12 exhibited the strongest decrease in expression level, which was selected for further study. We generated the Oskh12-knockout mutant via the CRISPR/Cas9 genome-editing method. Further stress treatment and biochemical assays confirmed that Oskh12 mutant was more salt-sensitive than Nip and the expression of several key salt-tolerant genes in Oskh12 was significantly reduced. Taken together, our results shed light on the understanding of the KH family and provide a theoretical basis for future abiotic stress studies in rice.

Phytoplankton are the foundation of marine ecosystems and play a crucial role in determining the optical properties of seawater, which are critical for remote sensing applications. However, passive remote sensing techniques are limited to obtaining data from the near surface, and cannot provide information on the vertical distribution of the subsurface phytoplankton. In contrast, active LiDAR technology can provide detailed profiles of the subsurface phytoplankton layer (SPL). Nevertheless, the large amount of data generated by LiDAR brought a challenge, as traditional methods for SPL detection often require manual inspection. In this study, we investigated the application of supervised machine learning algorithms for the automatic recognition of SPL, with the aim of reducing the workload of manual detection. We evaluated five machine learning models—support vector machine (SVM), linear discriminant analysis (LDA), a neural network, decision trees, and RUSBoost—and measured their performance using metrics such as precision, recall, and F3 score. The study results suggest that RUSBoost outperforms the other algorithms, consistently achieving the highest F3 score in most of the test cases, with the neural network coming in second. To improve accuracy, RUSBoost is preferred, while the neural network is more advantageous due to its faster processing time. Additionally, we explored the spatial patterns and diurnal fluctuations of SPL captured by LiDAR. This study revealed a more pronounced presence of SPL at night during this experiment, thereby demonstrating the efficacy of LiDAR technology in the monitoring of the daily dynamics of subsurface phytoplankton layers.

Sunflower (Helianthus annuus L.) is an important, substantial global oil crop with robust resilience to drought and salt stresses. The TGA (TGACG motif-binding factor) transcription factors, belonging to the basic region leucine zipper (bZIP) family, have been implicated in orchestrating multiple biological processes. Despite their functional significance, a comprehensive investigation of the TGA family’s abiotic stress tolerance in sunflowers remains elusive. In the present study, we identified 14 TGA proteins in the sunflower genome, which were unequally distributed across 17 chromosomes. Employing phylogenetic analysis encompassing 149 TGA members among 13 distinct species, we revealed the evolutionary conservation of TGA proteins across the plant kingdom. Collinearity analysis suggested that both HaTGA01 and HaTGA03 were generated due to HaTGA08 gene duplication. Notably, qRT-PCR analysis demonstrated that HaTGA04, HaTGA05, and HaTGA14 genes were remarkably upregulated under ABA, MeJA, and salt treatments, whereas HaTGA03, HaTGA06, and HaTGA07 were significantly repressed. This study contributes valuable perspectives on the potential roles of the HaTGA gene family under various stress conditions in sunflowers, thereby enhancing our understanding of TGA gene family dynamics and function within this agriculturally significant species.

Abstract A single base changes causing a change to the amino acid sequence of the encoded protein, which is defined as non-synonymous single nucleotide polymorphisms (nsSNPs). Many of the nsSNPs can cause disease, and these nsSNPs are considered as pathogenic mutations. In the study, the high-risk nsSNPs of WFS1 and their influence on the structure and function of wolframin protein were predicted by multiple bioinformatics software. We obtained 13 high-risk nsSNPs of WFS1. All the 13 high-risk nsSNPs are highly conserved residues with a conservative score of 9 or 8 and mostly may cause a decrease in protein stability. The high-risk nsSNPs have an important effect on not only amino acid size, charge and hydrophobicity, but also protein's spatial structure. Among these, 11 nsSNPs had been previously published or cited and 2 nsSNPs (G695S and E776K) had not been reported to date. The two novel variants increased or decreased hydrogen bonds. In conclusion, through different computational tools, it is presumed that the mechanism of pathogenic WFS1 nsSNPs should include the changes of physicochemical properties, significant structural changes and abnormal binding with functional partners. We accomplished the computational-based screening and analysis for deleterious nsSNPs in WFS1, which had important reference value and could contribute to further studies of the mechanism of WFS1 related disease. The computational analysis has many advantages, but the results should be identified by further experimental studies in vivo and in vitro.

Abstract Aims Diabetic cardiomyopathy (DCM) is one of the major cardiovascular complications of diabetes. However, the mechanism of DCM is not fully understood. Studies have confirmed that certain microRNAs (miRNAs/miRs) are key regulators of DCM. The aim of this study was to investigate the role and mechanism of microRNA (miR)‐494 in cardiomyocyte apoptosis and autophagy induced by high glucose (HG). Methods and results By establishing a rat DCM model and an HG‐treated H9c2 cells injury model, cardiac function was detected by echocardiography, myocardial tissue was stained by immunohistochemistry, and Cell Counting Kit‐8 assay and lactate dehydrogenase assay were used to detect the cardiomyocyte injury. Cell apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labelling staining, and western blotting was used to detect death and autophagy. The results showed that the expression level of miR‐494 was higher in the myocardial tissue of DCM rats and the myocardial cells of H9c2 treated with HG. Compared with the corresponding negative control groups, miR‐494 mimics enhanced HG‐induced apoptosis and autophagy, whereas miR‐494 inhibitors showed the opposite effect, corresponding PI3K, AKT, and mTOR phosphorylation level has changed. Conclusions These findings identify that miR‐494 could regulate cell apoptosis and autophagy through PI3K/AKT/mTOR signalling pathway, participating in the regulation of cardiomyocyte cell damage after HG. These findings provide new insights for the further study of the molecular mechanism and treatment of DCM.

Gastric cancer (GC) is a heterogeneous disease and a leading cause of cancer-related deaths. Discovering robust, clinically relevant molecular classifications is critical for guiding personalized therapies for GC. Here, we propose a refined molecular classification scheme for GC using integrated optimal algorithms and multi-omics data. Based on the important features of mRNA, microRNA, and DNA methylation data selected by the multivariate Cox regression model, three subtypes linked to distinct clinical outcomes were identified by combining similarity network fusion and consensus clustering methods. Three subtypes were validated by an extreme gradient boosting machine learning prediction model with 125 differentially expressed genes in multiple independent cohorts. The molecular characteristics of mutation signatures, characteristic gene sets, driver genes, and chemotherapy sensitivity for each subtype were also identified: subtype 1 was associated with favorable prognosis and characterized by high ARID1A and PIK3CA mutations, subtype 2 was associated with a poor prognosis and harbored high recurrent TP53 mutations, and subtype 3 was associated with high CHD1, APOA1 mutations, and a poor prognosis. The proposed three-subtype scheme achieved a better clinical prediction performance (area under the curve value = 0.71) than The Cancer Genome Atlas classification, which may provide a practical subtyping framework to improve the treatment of GC.

Summary: Background: Prognosis is crucial for personalized treatment and surveillance suggestion of the resected non-small-cell lung cancer (NSCLC) patients in stage I-III. Although the tumor-node-metastasis (TNM) staging system is a powerful predictor, it is not perfect enough to accurately distinguish all the patients, especially within the same TNM stage. In this study, we developed an intelligent prognosis evaluation system (IPES) using pre-therapy CT images to assist the traditional TNM staging system for more accurate prognosis prediction of resected NSCLC patients. Methods: 20,333 CT images of 6371 patients from June 12, 2009 to March 24, 2022 in West China Hospital of Sichuan University, Mianzhu People's Hospital, Peking University People's Hospital, Chengdu Shangjin Nanfu Hospital and Guangan Peoples' Hospital were included in this retrospective study. We developed the IPES based on self-supervised pre-training and multi-task learning, which aimed to predict an overall survival (OS) risk for each patient. We further evaluated the prognostic accuracy of the IPES and its ability to stratify NSCLC patients with the same TNM stage and with the same EGFR genotype. Findings: The IPES was able to predict OS risk for stage I-III resected NSCLC patients in the training set (C-index 0.806; 95% CI: 0.744–0.846), internal validation set (0.783; 95% CI: 0.744–0.825) and external validation set (0.817; 95% CI: 0.786–0.849). In addition, IPES performed well in early-stage (stage I) and EGFR genotype prediction. Furthermore, by adopting IPES-based survival score (IPES-score), resected NSCLC patients in the same stage or with the same EGFR genotype could be divided into low- and high-risk subgroups with good and poor prognosis, respectively (p

PurposeThe aim of this study was to analyze the relationship between diopter (D) and choroidal thickness in myopic children by describing the values of choroidal thickness, and explore choroidal thickness as an important indicator for evaluating the progression of myopia.MethodsThe study included myopic and emmetropic children aged 6–14 years (156 eyes) from the Second Hospital of Dalian Medical University. The participants were divided into four groups according to the spherical equivalent refraction (SER): low myopes, moderate myopes, high myopes, and emmetropes. Choroidal thickness was measured in nine areas using the Early Treatment Diabetic Retinopathy Study (ETDRS) grid layout, which divided the areas into concentric circles of 0 × 0 mm, 3 × 3 mm, and 5 × 5 mm from the Sub Fovea. The images were obtained manually with spectral-domain optical coherence tomography scanner.ResultsThere were significant differences of choroidal thickness in the nine areas of the ETDRS grid for all myopes. The distribution of choroidal thickness in low and moderate myopes were different from that in high myopes. In the horizontal direction, choroidal thickness decreased from the temporal to nasal areas for all myopes. In the vertical direction, the choroidal thickness in the perifovea was smaller than that in the parafovea (SER ≥ −2.75D), and the choroidal thickness in the perifovea was greater than that in the parafovea (SER

Fluopyram, a SDH inhibitor fungicide, is widely used in agriculture to control fungi and nematodes. However, fluopyram has been proved toxic that caused damage to organs through oxidative stress. The development of natural extracts that can reduce oxidative damage is a promising method. Lentinan is isolated from Lentinus edodes and has been verified its antioxidant activity. In this study, Caenorhabditis elegans was used to evaluate the protective effects of lentinan against fluopyram-induced toxicity and the possible mechanisms. Results showed that lentinan pretreatment notably increased the survival rate of N2 nematodes by 15.0 % and extended the lifespan by 91.5 %, compared with the fluopyram treatment. Lentinan pretreatment reverted the inhibition of the locomotion and reproduction of C. elegans under the fluopyram stress. In addition, lentinan pretreatment significantly decreased the contents of ROS and MDA in N2 nematodes. Moreover, pretreated with lentinan significantly recovered the decreased activities of CAT, SOD, GST and SDH induced by fluopyram. Lentinan pretreatment enhanced the mRNA levels of daf-16 and skn-1 and their downstream genes in the nematodes compared with the fluopyram group. In daf-16 and skn-1 mutants, the lifespan, ROS and related genes expression were not significantly changed in lentinan pretreatment. Pretreated with lentinan significantly enhanced the fluorescence intensity of SOD-3::GFP and GST-4::GFP, and promoted the nuclear translocation of DAF-16 and SKN-1 under the fluopyram stress. In summary, these findings indicated that lentinan protected C. elegans from fluopyram-induced toxicity via DAF-16 and SKN-1.

Melting furnace slag (MFS) is a potentially active by-product of the synergistic treatment of iron and steel dust sludge and Municipal Solid Waste (MSW) incineration fly ash in the flue gas magnetization fusion separator furnace of the “fire method + wet method”. This paper focuses on the MFS reactivated by mechanical grinding, and the reactivity of MFS is synergistically enhanced by alkaline, sulfate-based solid wastes. The particle size distribution, specific surface area, morphology, and physical phase composition of MFS with different grinding times resulted in the best performance of MFS when mechanically ground for 80 min and the specific surface area reached 450 m2/kg, and the reactivity indexes reached 100.94% and 103.7% for 7 and 28 d, respectively. The synergistic activation of steel slag and flue-gas desulfurization gypsum can play an effective role in stimulating the MFS, and the optimal proportion is m (MFS): m (SS): m (FGDG) = 42%: 42%: 16%. The reactivity enhancement mechanism of the ternary slag-based system on MFS: SS provides high alkalinity hydration reaction conditions for MFS and FGDG provides SO42−, which continuously promotes the hydrolysis of MFS under the synergistic reactivity stimulation to generate AFt and C–S–H gels.

Sepsis is a systemic inflammation caused by a maladjusted host response to infection. In severe cases, it can cause multiple organ dysfunction syndrome (MODS) and even endanger life. Acupuncture is widely accepted and applied in the treatment of sepsis, and breakthroughs have been made regarding its mechanism of action in recent years. In this review, we systematically discuss the current clinical applications of acupuncture in the treatment of sepsis and focus on the mechanisms of acupuncture in animal models of systemic inflammation. In clinical research, acupuncture can not only effectively inhibit excessive inflammatory reactions but also improve the immunosuppressive state of patients with sepsis, thus maintaining immune homeostasis. Mechanistically, a change in the acupoint microenvironment is the initial response link for acupuncture to take effect, whereas PROKR2 neurons, high-threshold thin nerve fibres, cannabinoid CB2 receptor (CB2R) activation, and Ca2+ influx are the key material bases. The cholinergic anti-inflammatory pathway of the vagus nervous system, the adrenal dopamine anti-inflammatory pathway, and the sympathetic nervous system are key to the transmission of acupuncture information and the inhibition of systemic inflammation. In MODS, acupuncture protects against septic organ damage by inhibiting excessive inflammatory reactions, resisting oxidative stress, protecting mitochondrial function, and reducing apoptosis and tissue or organ damage.

Background: Short-term associations between heat and cardiovascular disease (CVD) mortality have been examined mostly in large cities. However, different vulnerability and exposure levels may contribute to spatial heterogeneity. This study assessed heat effects on CVD mortality and potential vulnerability factors using data from three European countries, including urban and rural settings. Methods: We collected daily counts of CVD deaths aggregated at the small-area level in Norway (small-area level: municipality), England and Wales (lower super output areas), and Germany (district) during the warm season (May-September) from 1996 to 2018. Daily mean air temperatures estimated by spatial–temporal models were assigned to each small area. Within each country, we applied area-specific Quasi-Poisson regression using distributed lag nonlinear models to examine the heat effects at lag 0–1 days. The area-specific estimates were pooled by random-effects meta-analysis to derive country-specific and overall heat effects. We examined individual- and area-level heat vulnerability factors by subgroup analyses and meta-regression, respectively. Results: We included 2.84 million CVD deaths in analyses. For an increase in temperature from the 75th to the 99th percentile, the pooled relative risk (RR) for CVD mortality was 1.14 (95% CI: 1.03, 1.26), with the country-specific RRs ranging from 1.04 (1.00, 1.09) in Norway to 1.24 (1.23, 1.26) in Germany. Heat effects were stronger among women [RRs (95% CIs) for women and men: 1.18 (1.08, 1.28) vs. 1.12 (1.00, 1.24)]. Greater heat vulnerability was observed in areas with high population density, high degree of urbanization, low green coverage, and high levels of fine particulate matter. Conclusion: This study provides evidence for the heat effects on CVD mortality in European countries using high-resolution data from both urban and rural areas. Besides, we identified individual- and area-level heat vulnerability factors. Our findings may facilitate the development of heat-health action plans to increase resilience to climate change.

Abstract Mounting interest in modeling outdoor diffusion and transmission of bioaerosols due to the prevalence of COVID-19 in the urban environment has led to better knowledge of the issues concerning exposure risk and evacuation planning. In this study, the dispersion and deposition dynamics of bioaerosols around a vaccine factory were numerically investigated under various thermal conditions and leakage rates. To assess infection risk at the pedestrian level, the improved Wells-Riley equation was used. To predict the evacuation path, Dijkstra’s algorithm, a derived greedy algorithm based on the improved Wells-Riley equation, was applied. The results show that, driven by buoyancy force, the deposition of bioaerosols can reach 80 m on the windward sidewall of high-rise buildings. Compared with stable thermal stratification, the infection risk of unstable thermal stratification in the upstream portion of the study area can increase by 5.53% and 9.92% under a low and high leakage rate, respectively. A greater leakage rate leads to higher infection risk but a similar distribution of high-risk regions. The present work provides a promising approach for infection risk assessment and evacuation planning for the emergency response to urban bioaerosol leakage.

The classification of motor imagery-electroencephalogram(MI-EEG)based brain-computer interface(BCI)can be used to decode neurological activities, which has been widely applied in the control of external devices. However, two factors still hinder the improvement of classification accuracy and robustness, especially in multi-class tasks. First, existing algorithms are based on a single space (measuring or source space). They suffer from the holistic low spatial resolution of the measuring space or the locally high spatial resolution information accessed from the source space, failing to provide holistic and high-resolution representations. Second, the subject specificity is not sufficiently characterized, resulting in the loss of personalized intrinsic information. Therefore, we propose a cross-space convolutional neural network (CS-CNN) with customized characteristics for four-class MI-EEG classification. This algorithm uses the modified customized band common spatial patterns (CBCSP) and duplex mean-shift clustering (DMSClustering) to express the specific rhythms and source distribution information in cross-space. At the same time, multi-view features from the time, frequency and space domains are extracted, connecting with CNN to fuse the characteristics from two spaces and classify them. MI-EEG was collected from 20 subjects. Lastly, the classification accuracy of the proposed is 96.05% with real MRI information and 94.79% without MRI in the private dataset. And the results in the BCI competition IV-2a show that CS-CNN outperforms the state-of-the-art algorithms, achieving an accuracy improvement of 1.98%, and a standard deviation reduction of 5.15%.

Abstract To analyse the pathogenic genes and mutations of a family with hereditary deafness. We recruited a three-generation family with NSHL. A detailed medical history inquiry and related examinations were performed. Next-generation sequencing (NGS) was used to confirm the gene mutation in the proband, and Sanger sequencing was used for verification. The effect of the WFS1 mutation on the function and structure of the wolframin protein was predicted by multiple computational software. From the Gene Expression Omnibus (GEO) database, we obtained GSE40585 dataset and performed enrichment analyses. The family clinically manifested as autosomal dominant NSHL. A novel WFS1 c.2421C>G (p.Ser807Arg) mutation was identified in four affected individuals in the pedigree . The p.Ser807Arg mutation is a highly conserved residue and causes an increase in protein stability. It had an important influence on not only amino acid size, charge and hydrophobicity but also protein intermolecular hydrogen bonding and spatial structure. There were differentially expressed genes (DEGs) in GSE40585 dataset. Enrichment analysis revealed that DEGs mainly functioned in amino acid metabolism, signal transduction and dephosphorylation. We reported a novel mutation c.2421C>G (p.Ser807Arg in WFS1. This study expands the mutation spectrum of WFS1.

Isoflavones are predominantly found in legumes and play roles in plant defense and prevention of estrogen-related diseases. Genistein is an important isoflavone backbone with various biological activities. In this paper, we describe how a cell factory that can de novo synthesize genistein was constructed in Saccharomyces cerevisiae. Different combinations of isoflavone synthase, cytochrome P450 reductase, and 2-hydroxyisoflavone dehydratase were tested, followed by pathway multicopy integration, to stably de novo synthesize genistein. The catalytic activity of isoflavone synthase was enhanced by heme supply and an increased intracellular NADPH/NADP+ ratio. Redistribution of the malonyl-CoA flow and balance of metabolic fluxes were achieved by adjusting the fatty acid synthesis pathway, yielding 23.33 mg/L genistein. Finally, isoflavone glycosyltransferases were introduced into S. cerevisiae, and the optimized strain produced 15.80 mg/L of genistin or 10.03 mg/L of genistein-8-C-glucoside. This is the first de novo synthesis of genistein-8-C-glucoside in S. cerevisiae, which is advantageous for the green industrial production of isoflavone compounds.