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Abstract Background Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. Methods This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017–2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018–2021) and another from center 2 (n = 43, 2020–2021), were utilized to assess the signature’s association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. Results Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. Conclusion This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC’s MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.

Wooden breast barriers the development of broiler industry, and traditional detection methods are time-consuming and inefficient. To investigate the feasibility of the hyperspectral imaging (HSI) technique for the detection of wooden breasts, four different grades of white feather chicken breast were selected and their HSI information of 400~1000 and 1000~2000 nm was collected. After spectral preprocessing and spectral variable selection, partial least squares discriminant (PLS-DA) models and support vector machine (SVM) models were developed based on full wavelength and characteristic spectral variables, as well as their fused HSI data. The results showed that SVM models showed better results than PLS-DA models to discriminate woody grades of chicken breasts. The overall discrimination rates based on the full HSI bands and selected spectral variables in 1000~2000 nm were higher than those of models in 400~1000 nm. Besides, the discrimination models based on fused HSI data of HSI bands and selected spectral variables provided the best results, with the overall discrimination rate of 96.7% for four different woody grades, and the accuracy of the four grades could reach more than 90%. The research results provided technical support for HSI to achieve rapid and non-destructive detection of wooden chicken breasts.

Supported by GNSS, it analyzed the advantages and disadvantages of solving LEO satellite orbit on the ground or onboard the satellites.The high-fidelity non-conservative force models were applied to the real-time orbit determination algorithm.To separate the kinematic and dynamic orbit determination process had been a great advantage for LEO satellites with much frequent orbital maneuvers.The test results showed that the accuracy of accelerations computed from the radiation pressure and atmospheric drag non-conservation force models were around 5 nm/s2.Use the broadcast ephemeris, the real-time orbit determination algorithm could get an accuracy of 0.8 m in the satellites′ positions and 1.1 mm/s accuracy in the satellites′ velocity.When the real-time precise ephemeris of GNSS satellites were provided, the algorithm could get an accuracy of 8 cm in the LEO satellites′ position and 0.1 mm/s in the velocity.The method for real-time orbit determination and orbit prediction in this paper could be used to support the construction of navigation system with the mega-constellations.

This paper proposed a Doppler-only point-solution algorithm and analyzed the Doppler positioning performance based on the Starlink constellation.The Doppler positioning accuracy was about 3～6 m.To achieve the meter-level positioning accuracy, the satellite position and velocity errors should be within several meters and several centimeters per second, respectively.The ionospheric delay rates of C-band signal would cause about 2 m error in Doppler positioning.The positioning error would increase by dozens of meters if there were no corrections for the tropospheric errors.To ensure convergence in the LEO-based Doppler positioning, the initial receiver position error should be less than 300 km when the satellites orbit at an altitude of 550 km.

Using two routes, this study designed and synthesized a novel azo-linked four-heterocyclic compound, 1,2-bis(5-(1H-tetrazol-5-yl)-4H-1,2,4-triazol-3-yl) diazene (3, H4BTTD), with high yields. It corroborated that large conjugated planar energetic molecules in energetic compounds, exemplified by H4BTTD, contribute to the formation of layered crystal stacking based on abundant hydrogen bonds and interlayer π-π interactions. This markedly diminishes the mechanical sensitivities of energetic compounds. Single-crystal X-ray diffraction (XRD) experiments revealed the presence of layered structures in H4BTTD hydrate, as well as its magnesium-based complex [Mg2(BTTD)(H2O)8] (4) and calcium salt [Ca(H2O)7] (H3BTTD)2 (5). Based on these structural data, this study analyzed the causes of these layered structures. Furthermore, this study systematically characterized the compounds’ physical and chemical properties, including mechanical sensitivities (IS ≥ 20 J, FS > 360 N), thermal stability (Td = 253.7–287.8 °C), and detonation performance (D = 6808–8253 m⋅s−1), confirming the influence of molecular structures on the macroscopic properties of energetic materials through crystal stacking. Additionally, pyrotechnic formulas based on compounds 3 and 5 exhibited the most intense light emission within a wavelength range of 658.6–689.8 nm, underscoring the potential application of both compounds as promising candidates in preparing high-purity red pyrotechnic formulation.

Abstract Low-dimensional/three-dimensional perovskite heterojunctions have shown great potential for improving the performance of perovskite photovoltaics, but large organic cations in low-dimensional perovskites hinder charge transport and cause carrier mobility anisotropy at the heterojunction interface. Here, we report a low-dimensional/three-dimensional perovskite heterojunction that introduces strong aromatic conjugated low-dimensional perovskites in p-i-n devices to reduce the electron transport resistance crossing the perovskite/electron extraction interface. The strong aromatic conjugated π-conjugated network results in continuous energy orbits among [Pb2I6]2− frameworks, thereby effectively suppressing interfacial non-radiative recombination and boosting carrier extraction. Consequently, the devices achieved an improved efficiency to 25.66% (certified 25.20%), and maintained over 95% of the initial efficiency after 1200 hours and 1000 hours under ISOS-L-1I and ISOS-D-1 protocols, respectively. The chemical design of strong aromatic conjugated molecules in perovskite heterojunctions provides a promising avenue for developing efficient and stable perovskite photovoltaics.

Abstract Background Myasthenia gravis (MG) is a chronic autoimmune disorder characterized by fluctuating muscle weakness. Despite the availability of established therapies, the management of MG symptoms remains suboptimal, partially attributed to lack of efficacy or intolerable side-effects. Therefore, new effective drugs are warranted for treatment of MG. Methods By employing an analytical framework that combines Mendelian randomization (MR) and colocalization analysis, we estimate the causal effects of blood druggable expression quantitative trait loci (eQTLs) and protein quantitative trait loci (pQTLs) on the susceptibility of MG. We subsequently investigated whether potential genetic effects exhibit cell-type specificity by utilizing genetic colocalization analysis to assess the interplay between immune-cell-specific eQTLs and MG risk. Results We identified significant MR results for four genes (CDC42BPB, CD226, PRSS36, and TNFSF12) using cis-eQTL genetic instruments and three proteins (CTSH, PRSS8, and CPN2) using cis-pQTL genetic instruments. Six of these loci demonstrated evidence of colocalization with MG susceptibility (posterior probability > 0.80). We next undertook genetic colocalization to investigate cell-type-specific effects at these loci. Notably, we identified robust evidence of colocalization, with a posterior probability of 0.854, linking CTSH expression in TH2 cells and MG risk. Conclusions This study provides crucial insights into the genetic and molecular factors associated with MG susceptibility, singling out CTSH as a potential candidate for in-depth investigation and clinical consideration. It additionally sheds light on the immune-cell regulatory mechanisms related to the disease. However, further research is imperative to validate these targets and evaluate their feasibility for drug development.

Abstract Background The neural cells in the brains of patients with Parkinson’s disease (PWP) display aberrant synchronized oscillatory activity within the beta frequency range. Additionally, enhanced gamma oscillations may serve as a compensatory mechanism for motor inhibition mediated by beta activity and also reinstate plasticity in the primary motor cortex affected by Parkinson’s disease. Transcranial alternating current stimulation (tACS) can synchronize endogenous oscillations with exogenous rhythms, thereby modulating cortical activity. The objective of this study is to investigate whether the addition of tACS to multidisciplinary intensive rehabilitation treatment (MIRT) can improve symptoms of PWP so as to enhance the quality of life in individuals with Parkinson’s disease based on the central-peripheral-central theory. Methods The present study was a randomized, double-blind trial that enrolled 60 individuals with Parkinson’s disease aged between 45 and 70 years, who had Hoehn-Yahr scale scores ranging from 1 to 3. Participants were randomly assigned in a 1:1 ratio to either the tACS + MIRT group or the sham-tACS + MIRT group. The trial consisted of a two-week double-blind treatment period followed by a 24-week follow-up period, resulting in a total duration of twenty-six weeks. The primary outcome measured the change in PDQ-39 scores from baseline (T0) to 4 weeks (T2), 12 weeks (T3), and 24 weeks (T4) after completion of the intervention. The secondary outcome assessed changes in MDS-UPDRS III scores at T0, the end of intervention (T1), T2, T3, and T4. Additional clinical assessments and mechanistic studies were conducted as tertiary outcomes. Discussion The objective of this study is to demonstrate that tACS can enhance overall functionality and improve quality of life in PWP, based on the framework of MIRT. Additionally, it seeks to establish a potential correlation between these therapeutic effects and neuroplasticity alterations in relevant brain regions. The efficacy of tACS will be assessed during the follow-up period in order to optimize neuroplasticity and enhance its potential impact on rehabilitation efficiency for PWP. Trial registration Chinese Clinical Trial Registry ChiCTR2300071969. Registered on 30 May 2023.

Abstract. Background:. Total human immunodeficiency virus (HIV) DNA and integrated HIV DNA are widely used markers of HIV persistence. Droplet digital polymerase chain reaction (ddPCR) can be used for absolute quantification without needing a standard curve. Here, we developed duplex ddPCR assays to detect and quantify total HIV DNA and integrated HIV DNA. Methods:. The limit of detection, dynamic ranges, sensitivity, and reproducibility were evaluated by plasmid constructs containing both the HIV long terminal repeat (LTR) and human CD3 gene (for total HIV DNA) and ACH-2 cells (for integrated HIV DNA). Forty-two cases on stable suppressive antiretroviral therapy (ART) were assayed in total HIV DNA and integrated HIV DNA. Correlation coefficient analysis was performed on the data related to DNA copies and cluster of differentiation 4 positive (CD4+) T-cell counts, CD8+ T-cell counts and CD4/CD8 T-cell ratio, respectively. The assay linear dynamic range and lower limit of detection (LLOD) were also assessed. Results:. The assay could detect the presence of HIV-1 copies 100% at concentrations of 6.3 copies/reaction, and the estimated LLOD of the ddPCR assay was 4.4 HIV DNA copies/reaction (95% confidence intervals [CI]: 3.6–6.5 copies/reaction) with linearity over a 5-log10-unit range in total HIV DNA assay. For the integrated HIV DNA assay, the LLOD was 8.0 copies/reaction (95% CI: 5.8–16.6 copies/reaction) with linearity over a 3-log10-unit range. Total HIV DNA in CD4+ T cells was positively associated with integrated HIV DNA (r = 0.76, P

Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive types of squamous cell carcinoma and represents a significant proportion of esophageal cancer. Metabolic reprogramming plays a key role in the occurrence and development of ESCC. Unsupervised clustering analysis was employed to stratify ESCC samples into three clusters: MPC1-lipid type, MPC2-amino acid type, and MPC3-energy type, based on the enrichment scores of metabolic pathways extracted from the Reactome database. The MPC3 cluster exhibited characteristics of energy metabolism, with heightened glycolysis, cofactors, and nucleotide metabolism, showing a trend toward increased aggressiveness and poorer survival rates. On the other hand, MPC1 and MPC2 primarily involved lipid and amino acid metabolism, respectively. In addition, liquid chromatography‒mass spectrometry-based metabolite profiles and potential therapeutic agents were explored and compared among ESCC cell lines with different MPCs. MPC3 amplified energy metabolism markers, especially carnitines. In contrast, MPC1 and MPC2 predominantly had elevated levels of lipids (primarily triacylglycerol) and amino acids, respectively. Furthermore, MPC3 demonstrated a suboptimal clinical response to PD-L1 immunotherapy but showed increased sensitivity to the doramapimod chemotherapy regimen, as evident from drug sensitivity evaluations. These insights pave the way for a more personalized therapeutic approach, potentially enhancing treatment precision for ESCC patients.

Abstract Objectives To achieve automated quantification of visceral adipose tissue (VAT) distribution in CT images and screen out parameters with discriminative value for inflammatory bowel disease (IBD) subtypes. Methods This retrospective multicenter study included Crohn’s disease (CD) and ulcerative colitis (UC) patients from three institutions between 2012 and 2021, with patients with acute appendicitis as controls. An automatic VAT segmentation algorithm was developed using abdominal CT scans. The VAT volume, as well as the coefficient of variation (CV) of areas within the lumbar region, was calculated. Binary logistic regression and receiver operating characteristic analysis was performed to evaluate the potential of indicators to distinguish between IBD subtypes. Results The study included 772 patients (365 CDs, median age [inter-quartile range] = 31.0. (25.0, 42.0) years, 255 males; 241 UCs, 46.0 (34.0, 55.5) years, 138 males; 166 controls, 40.0 (29.0, 53.0) years, 80 males). CD patients had lower VAT volume (CD = 1584.95 ± 1128.31 cm3, UC = 1855.30 ± 1326.12 cm3, controls = 2470.91 ± 1646.42 cm3) but a higher CV (CD = 29.42 ± 15.54 %, p = 0.006 and p ˂ 0.001) compared to UC and controls (25.69 ± 12.61 % vs. 23.42 ± 15.62 %, p = 0.11). Multivariate analysis showed CV was a significant predictor for CD (odds ratio = 6.05 (1.17, 31.12), p = 0.03). The inclusion of CV improved diagnostic efficiency (AUC = 0.811 (0.774, 0.844) vs. 0.803 (0.766, 0.836), p = 0.08). Conclusion CT-based VAT distribution can serve as a potential biomarker for distinguishing IBD subtypes. Critical relevance statement Visceral fat distribution features extracted from CT images using an automated segmentation algorithm (1.14 min) show differences between Crohn’s disease and ulcerative colitis and are promising for practical radiological screening. Key points • Radiological parameters reflecting visceral fat distribution were extracted for the discrimination of Crohn’s disease (CD) and ulcerative colitis (UC). • In CD, visceral fat was concentrated in the lower lumbar vertebrae, and the coefficient of variation was a significant predictor (OR = 6.05 (1.17, 31.12), p = 0.03). • The differences between CD, UC, and controls are promising for practical radiological screening. Graphical Abstract

A comparison was conducted on the microstructure, mechanical properties, and corrosion resistance of the fusion zone (FZ) in Zr R60702 laser lap joints prepared under air-cooled and water-cooled conditions. The results reveal that the upper and lower regions of the FZ in the welded joint consist of dendritic structure and α′ martensite, respectively. When water-cooled forced cooling is applied, α′ martensite emerges in the upper region of the FZ, with a few dendrites exhibiting an isoaxial distribution. Furthermore, the α′ martensite in the lower region becomes noticeably refined. The utilization of water-cooling triggers multiple strengthening mechanisms that, through synergistic interactions, enhance the microhardness, strength, and plasticity of the welded joints. The improved corrosion resistance within the FZ of the welded joint is attributed to the formation of a more stable passivation film.

A nonlinear dynamic model of angular contact ball bearing under combined external loads is established based on the nonlinear elastic Hertz contact theory and raceless control theory. The established dynamic model is solved by employing variable step size Newton Raphson iteration method and the validation of model is verified by comparing the proposed results with the corresponding results come from the existing literatures. The solution of the presented model has high accuracy compared with the existing experimental results. In addition, the computational efficiency of the proposed model is improved significantly by introducing iteration step size adjustment factor. According to the proposed model, the dynamic contact and stiffness characteristics of angular contact ball are studied systematically by investigating the effects of combined external load working conditions on the contact parameters including contact angle and contact force and the stiffness parameters including diagonal stiffness and off-diagonal stiffness. This research can provide the theoretical basis and technique guidance for the designation and manufacture of angular contact ball bearing under combined external loads.

Daocai is a traditional salted pickle in the southeastern region of Guizhou with a unique aroma, color, and taste. The quality of Daocai is greatly influenced by the fermentation temperature. In this study, high-throughput sequencing and headspace-gas chromatography-ion mobility spectrometry were used to investigate the changes in microbial community succession and volatile flavor compounds during Daocai fermentation under temperature-controlled (D group) and non-temperature-controlled (C group).We found that the predominant genera in the C group samples were Latilactobacillus(40.57 %), Leuconostoc(21.25 %), Cystofilobasidium(22.12 %), Vishniacozyma(23.89 %), and Leucosporidium(24.95 %), whereas Weissella(29.39 %), Lactiplantibacillus(45.61 %), Mucor(68.26 %), and Saccharomyces(23.94 %) were the predominant genera in the D group. A total of 92 VFCs were detected in Daocai samples, including 5 isothiocyanates, 16 esters, 14 alcohols, 24 aldehydes, 17 ketones, 3 acids, 2 pyrazines, 1 pyridines, 1 thiazoles, 3 furans, 4 alkenes, and 2 nitriles. Further analysis revealed Latilactobacillus, Leuconostoc, Lactococcus, Cystofilobasidium, Leucosporidium, Holtermanniella, and Dioszegia as key bacteria involved in flavor formation. They are closely related to the formation of flavors such as aldehydes, furans, pyridines, and alkenes. This study contributes to our understanding of the relationship between bacterial communities and the flavor formation during Daocai fermentation.

In the MODIS snow product collection 6.1 (C6.1), some snowy pixels are misclassified as cloud pixels due to an excessive cloud mask algorithm. This increases cloud contamination in normalized difference snow index (NDSI) and affects snow mapping accuracy. Northeast China is used as an example to develop excessive cloud mask removal and gap-filling algorithms, and generate a daily cloud-free NDSI dataset for each snow season from 2001 to 2020. To identify pseudo-cloud pixels, the green band and NDSI were used to distinguish forested snow and clouds, thin snow in plains and clouds, respectively. This decreased cloud from nearly 60% to below 30%. We developed a spatiotemporal cube cloud removal algorithm based on NDSI similarity (STNSI) for the remaining clouds in which the central cloudy pixel was filled with neighborhood pixels in the spatiotemporal cube. Meanwhile, bias correction was performed, and the average cloud decreased to below 1% after the first iteration. The produced STNSI NDSI has high precision under different underlying surfaces, with OA and FS values greater than 0.9. Compared with the existing STAR NDSI, STNSI NDSI snow mapping accuracy improved, especially in forested areas where OA improved by 37%. Moreover, removing many pseudo-cloud pixels greatly enhances gap-filling efficiency.

Intramuscular fat (IMF) content is a predominant factor recognized to affect rabbit meat quality, directly impacting flavor, juiciness, and consumer preference. Despite its significance, the major interplay of genetic and epigenetic factors regulating IMF in rabbits remains largely unexplored. This review sheds light on this critical knowledge gap, offering valuable insights and future directions. We delve into the potential role of established candidate genes from other livestock (e.g. PPARγ, FABP4, and SCD) in rabbits, while exploring the identified novel genes of IMF in rabbits. Furthermore, we explored the quantitative trait loci studies in rabbit IMF and genomic selection approaches for improving IMF content in rabbits. Beyond genetics, this review unveils the exciting realm of epigenetic mechanisms modulating IMF deposition. We explored the potential of DNA methylation patterns, histone modifications, and non-coding RNA-mediation as fingerprints for selecting rabbits with desirable IMF levels. Additionally, we explored the possibility of manipulating the epigenetic landscape through nutraceuticals interventions to promote favorable IMF depositions. By comprehensively deciphering the genomic and epigenetic terrain of rabbit intramuscular fat regulation, this study aims to assess the existing knowledge regarding the genetic and epigenetic factors that control the deposition of intramuscular fat in rabbits. By doing so, we identified gaps in the current research, and suggested potential areas for further investigation that would enhance the quality of rabbit meat. This can enable breeders to develop targeted breeding strategies, optimize nutrition, and create innovative interventions to enhance the quality of rabbit meat, meet consumer demands and increase market competitiveness.

Limestone calcined clay cement (LC3) is one kind of the low-carbon binder in the recent years, contributing significantly to sustainable construction practice. This paper investigated the possibility of using the recycled powder from waste concrete as a substitution for limestone in the LC3. The results show that the mixtures containing equal amount of recycled powder demonstrate comparable rheological and mechanical properties to those containing limestone. The drying shrinkage of mortar with 30 % recycled powder was higher than the reference cement mortar, but the value at 90 ages decreased 18.75 % with the combination of calcined clay. The increasing of the normalized heat evolution for LC3 mixes was resulted from the filler effects provided by finer recycled powder and its sequential hydration with calcined clay. Compared to hydrated LC3 with limestone, the hydrated ternary system with recycled powder exhibits decreased formation of hemi- and mono-carboaluminate. The findings of this paper suggest that recycled powder exhibits considerable promise as a substitute for limestone in the production of LC3 and promoting carbon capture, utilization and storage (CCUS) of cement industry.

Efflux pumps play a crucial role in the development of antibiotic resistance. The aim of this study was to investigate the relationship between efflux pump gene expression and resistance gene mutations in Helicobacter pylori. Twenty-six clinical strains with varying resistance characteristics were selected for further experiment. Seven susceptible strains were induced to become resistant, and the expression of efflux pump genes and point mutations were recorded. Four susceptible strains were selected to undergo candidate mutation construction, and changes in efflux pump gene expression were detected. Efflux pump knockout strains were constructed, and their effects on preventing and reversing antibiotic resistance gene mutations were assessed. Results showed that the expression of efflux pump genes hefA and hefD was significantly higher in the multidrug-resistant group compared to other groups. During the process of antibiotic-induced resistance, efflux pump gene expression did not exhibit a steady increase or decrease. Strains with the A2143G or A2142G point mutations in 23S rRNA exhibited lower hefA gene expression. Strains with mutations at 87K/91N, 87N/91 G, 87K/91D, or 87N/91Y in gyrA and the 194insertA mutation in rdxA showed higher hefA gene expression compared to the wild-type strain. During the process of antibiotic-induced resistance, the strain with the knockout of the efflux pump gene hefA developed mutations in the 23S rRNA, gyrA, or rdxA genes later compared to the wild-type strain. Knockout of the efflux pump gene could reverse the phenotypic resistance to clarithromycin or metronidazole in some strains but had no effect on reverse resistance gene mutation. This study suggested that different resistance gene point mutations may have varying effects on efflux pump gene expression. Knockout of the efflux pump gene can delay or prevent antibiotic resistance gene mutations to some extent and can reverse phenotypic resistance to clarithromycin and metronidazole in certain strains.

Lupus, a systemic autoimmune disease shaped by gene-environment interplay, often progresses to endstage renal failure. While subchronic systemic exposure to bacterial lipopolysaccharide (LPS) triggers autoimmunity and glomerulonephritis in lupus-prone mice, it is unknown if inhaling LPS, which is common in certain occupations, can similarly trigger lupus. Here we determined how subchronic intranasal (IN) LPS instillation influences autoimmunity and glomerulonephritis development in lupusprone NZBWF1 female mice. Briefly, mice were IN-instilled with vehicle or E. coli LPS (0.8 μg/g) twice weekly for 5 wk, followed by necropsy. For systemic comparison, additional cohorts of mice were injected with LPS intraperitoneally (IP) using identical doses/timing. Lungs were assessed for inflammatory and autoimmune responses and then related to systemic autoimmunity and glomerulonephritis. IN/LPS exposure induced in the lung: i) leukocyte infiltration, ii)mRNA signatures for cytokines, chemokines, IFN-regulated, and cell death-related genes, iii) ectopic lymphoid tissue formation, and iv)diverse IgM and IgG autoantibodies (AAbs). Pulmonary effects coincided with enlarged spleens, elevated plasma IgG AAbs, and inflamed IgG-containing kidney glomeruli. In contrast, IP/LPS treatment induced systemic autoimmunity and glomerulonephritis without pulmonary manifestations. Taken together, these preclinical findings suggest the lung could serve as a critical nexus for triggering autoimmunity by respirable LPS in genetically predisposed individuals.

Purpose Dentin hypersensitivity (DH) is a prevalent condition, but long-term effective treatments are scarce. Differentiation of odontoblast-like cells is promising for inducing tertiary dentinogenesis and ensuring sustained therapeutic efficacy against DH. This study examined the effects and mechanism of action of mild heat stress (MHS) on the differentiation of odontoblast-like MDPC-23 cells.Methods We used a heating device to accurately control the temperature and duration, mimicking the thermal microenvironment of odontoblast-like cells. Using this device, the effects of MHS on cell viability and differentiation were examined. Cell viability was assessed using the MTT assay. The expression and nucleoplasmic ratio of the yes-associated protein (YAP) were examined by western blotting and immunofluorescence. The gene expression levels of heat shock proteins (HSPs) and dentin matrix protein-1 (DMP1) were measured using qPCR. Dentin sialophosphoprotein (DSPP) expression was evaluated using immunofluorescence and immunoblotting. Verteporfin was used to inhibit YAP activity.Results Mild heat stress (MHS) enhanced the odontoblast differentiation of MDPC-23 cells while maintaining cell viability. MHS also increased YAP activity, as well as the levels of HSP25 mRNA, HSP70 mRNA, HSP90α mRNA, DMP1 mRNA, and DSPP protein. However, after YAP inhibition, both cell viability and the levels of HSP90α mRNA, DMP1 mRNA, and DSPP protein were reduced.Conclusion YAP plays a crucial role in maintaining cell viability and promoting odontoblast differentiation of MDPC-23 cells under MHS. Consequently, MHS is a potential therapeutic strategy for DH, and boosting YAP activity could be beneficial for maintaining cell viability and promoting odontoblast differentiation.

ABSTRACTThis study aimed to elucidate the seroprevalence of antibodies to tetanus and pertussis among Chinese health care workers. Blood specimens from health care workers were collected during the 2021 annual medical examination at the First People’s Hospital of Wuhu. Commercial ELISA kits were employed to quantify serum IgG antibodies against tetanus toxin (anti-TT IgG) and both IgG and IgA antibodies against pertussis toxin (anti-PT IgG, anti-PT IgA). A concentration of anti-TT IgG exceeding 0.1 IU/ml was deemed seroprotective against tetanus, while concentrations of anti-PT IgG ≥ 50 IU/ml or anti-PT IgA ≥ 15 IU/ml were indicative of a prior pertussis infection. The overall seroprotective rate for anti-TT IgG stood at 10.43% (92/882), with the highest seroprotective rate (13.91%) in the 20–29 age group, followed by the 30–39 age group (10.57%), 40–49 age group (5.80%), and 50–59 age group (5.63%). Eighteen (2.04%) of the studied subjects were positive to anti-PT IgG, and the positive rate in 20–39 age group and 40–59 age group was 1.19% (8/673) and 4.78% (10/209), respectively. Thirty (3.40%) subjects displayed anti-PT IgG levels ≥100 IU/ml and/or anti-PT IgA ≥ 15 IU/ml, suggesting a recent pertussis infection within the preceding year. Over half (503/882, 57.03%) had undetectable anti-PT IgG antibodies. The majority of health care workers in China appear susceptible to tetanus and pertussis, and a significant subset has experienced pertussis infection. The implementation of booster vaccinations against these diseases for Chinese health care workers is recommended.

Delayed graft function (DGF) is an early complication after kidney transplantation. The literature on DGF has experienced substantial growth. However, there is a lack of bibliometric analysis of DGF. This study aimed to analyze the scientific outputs of DGF and explore its hotspots from 2013 to 2023 by using CiteSpace and VOSviewer. The 2058 pieces of literature collected in the Web of Science Core Collection (WOSCC) from 1 January 2013 to 31 December 2023 were visually analyzed in terms of the annual number of publications, authors, countries, journals, literature co-citations, and keyword clustering by using CiteSpace and VOSviewer. We found that the number of papers published in the past ten years showed a trend of first increasing and then decreasing; 2021 was the year with the most posts. The largest number of papers was published by the University of California System, and the largest number of papers was published by the United States. The top five keyword frequency rankings are: ‘delayed graft function’, ‘kidney transplantation’, ‘renal transplantation’, ‘survival’, and ‘recipients’. These emerging trends include ‘brain death donors’, ‘blood absence re-injection injuries’, ‘tacrolimus’, ‘older donors and recipients’, and ‘artificial intelligence and DGF’. In summary, this study reveals the authors and institutions that could be cooperated with and discusses the research hotspots in the past ten years. It provides a reference and direction for future research and application of DGF.

Karst cave causes geological disasters in tunneling engineering, which brings great risks to subway construction. The microtremor survey has become one of the main methods for karst cave detection in urban areas due to its convenience and great detection depth. However, the microtremor survey lacks high-frequency signals, resulting in poor detection accuracy on the shallow layer. An advanced method called mixed-source surface wave (MSW) method is proposed by imposing active sources during the continuous passive surface wave survey. MSW is applied to the detection of beaded karst caves (i.e. two or three karst caves at different depths in the same location) in Ji'nan, China. The influences of ambient noise, array type, and other factors on the detection accuracy were studied. Experimental results show that the detection depth and accuracy of MSW are much better than those of passive surface wave method. The inversion accuracy of linear array perpendicular to road is better than the triangle array and L-shaped array. The accuracy of the linear array along the road is worst. The detection accuracy of MSW is similar to that of combined active–passive surface wave methods. However, the basic principle of MSW is easier to understand, and its operation is more convenient. The two-dimensional measurement results show that the MSW method can well reflect the size and location of the beaded karst cave and provide important references for the practical engineering.

Foot-and-mouth disease virus (FMDV) 2C protein is a conserved non-structural protein and crucial for replication of the virus. In this study, FMDV 2C protein was prepared and the enzymatic activities were investigated in detail. The protein could digest ssDNA or ssRNA into a small fragment at about 10 nt, indicating that the protein has nuclease activity. But it did not show digestion to blunt-end dsDNA or dsRNA. The nuclease activity of 2C protein could be inhibited in 2 mM Zn2+ or Ca2+ while enhanced by Mg2+ or Mn2+. FMDV 2C protein exhibited unwinding activity to all the three kinds of dsDNA and dsRNA (5′ protruded, 3′ protruded, and blunt-end). The unwinding velocity to 5′ protruded dsRNA was higher than to the blunt-end dsRNA. 2C protein only showed unwinding activity in high concentration of Mg2+, but no unwinding activity in physiological concentrations of Mg2+ and Ca2+, as well as in cell lysate. The 2C protein could catalyze two structured ssRNA to form double strand, thus it was proved to have RNA chaperone activity. The Mg2+ and ATP in different concentrations did not show promotion to the RNA chaperone activity. Finally, six mutant proteins (K116A, D160A, D170A, N207A, R226A, and F316A) were constructed and the enzymatic activities were analyzed. All the six mutations reduced the ATPase activity, D170A and F361A could inactivate the nuclease activity, while the N207A and F316A could inactivate the helicase activity. Our study provides a comprehensive understanding of the enzymatic activities of FMDV 2C protein.

Abstract An efficient method for the synthesis of a self‐supporting carbon framework (denoted Gra‐GC‐MoSe2) is proposed with a triple‐gradient structure—in sodiophilic sites, pore volume, and electrical conductivity—which facilitates the highly efficient regulation of Na deposition. In situ and ex situ measurements, together with theoretical calculations, reveal that the gradient distribution of Se heteroatoms in MoSe2, and its derivatives tailor the sodiophilicity, while the gradient distribution of porous nanostructures homogenizes the Na+ diffusion. Therefore, Na deposition occurs from the bottom to the top of the Gra‐GC‐MoSe2 framework without dendrite formation. In addition, the gradient in electrical conductivity ensures the stripping process does not lead to dead Na. As a result, a Gra‐GC‐MoSe2 modified Na anode (Na@Gra‐GC‐MoSe2) shows impressive cycling stability with a high average Coulombic efficiency in an asymmetric cell. In symmetric cells, it also exhibits a long cycling life of 2000 h with a low polarization voltage and works stably even under a large capacity of 10 mAh cm−2. Moreover, a Na@Gra‐GC‐MoSe2|| Na3V2(PO4)3 full cell delivers a high energy density with an excellent cycling performance.

IntroductionWalnut green husk (WGH) is a waste byproduct from walnut industry. However, it is not well-known about its bioactive effect on human gut health.MethodsThis study conducted in vitro digestion and fermentation experiments to study the bioactive effect of WGH.ResultsMicrobial fermentation was the primary mechanism to efficiently release phenolics and flavonoids, resulting in more excellent antioxidant capacities (DPPH, ABTS, and FRAP assays), which reached a highest value with 14.82 ± 0.01 mg VcE/g DW, 3.47 ± 0.01 mmol TE/g DW, and 0.96 ± 0.07 mmol FeSO4·7H2O/g DW, respectively. The surface microstructure of WGH became loose and fragmented after microbial fermentation. The analytical results of gut microbiota demonstrated that WGH could significantly increase the relative abundance of Proteobacteria in phylum level and Phascolarctobacterium in genus level while certain pro-inflammatory bacteria (such as Clostridium_sensu_stricto_1, Dorea, Alistipes, and Bilophila) was inhibited. Additionally, 1,373 differential metabolites were identified and enriched in 283 KEGG pathways. Of which some metabolites were significantly upregulated including ferulic acid, chlorogenic acid, umbelliferone, scopolin, muricholic acid, and so forth.DiscussionThese results indicated that WGH could have antioxidant and anti-inflammatory activities in the human gut, which could improve the economical value of WGH in the food industry.

IntroductionRadiation therapy (RT) is one of the primary treatment options for early-stage non-small cell lung cancer (ES-NSCLC). Therefore, accurately predicting the overall survival (OS) rate following radiotherapy is crucial for implementing personalized treatment strategies. This work aims to develop a dual-radiomics (DR) model to (1) predict 3-year OS in ES-NSCLC patients receiving RT using pre-treatment CT images, and (2) provide explanations between feature importanceand model prediction performance.MethodsThe publicly available TCIA Lung1 dataset with 132 ES-NSCLC patients received RT were studied: 89/43 patients in the under/over 3-year OS group. For each patient, two types of radiomic features were examined: 56 handcrafted radiomic features (HRFs) extracted within gross tumor volume, and 512 image deep features (IDFs) extracted using a pre-trained U-Net encoder. They were combined as inputs to an explainable boosting machine (EBM) model for OS prediction. The EBM’s mean absolute scores for HRFs and IDFs were used as feature importance explanations. To evaluate identified feature importance, the DR model was compared with EBM using either (1) key or (2) non-key feature type only. Comparison studies with other models, including supporting vector machine (SVM) and random forest (RF), were also included. The performance was evaluated by the area under the receiver operating characteristic curve (AUCROC), accuracy, sensitivity, and specificity with a 100-fold Monte Carlo cross-validation.ResultsThe DR model showed highestperformance in predicting 3-year OS (AUCROC=0.81 ± 0.04), and EBM scores suggested that IDFs showed significantly greater importance (normalized mean score=0.0019) than HRFs (score=0.0008). The comparison studies showed that EBM with key feature type (IDFs-only demonstrated comparable AUCROC results (0.81 ± 0.04), while EBM with non-key feature type (HRFs-only) showed limited AUCROC (0.64 ± 0.10). The results suggested that feature importance score identified by EBM is highly correlated with OS prediction performance. Both SVM and RF models were unable to explain key feature type while showing limited overall AUCROC=0.66 ± 0.07 and 0.77 ± 0.06, respectively. Accuracy, sensitivity, and specificity showed a similar trend.DiscussionIn conclusion, a DR model was successfully developed to predict ES-NSCLC OS based on pre-treatment CT images. The results suggested that the feature importance from DR model is highly correlated to the model prediction power.

Abstract Ultrasound (US), as a non‐invasive mechanical wave, has served as a visual tool for medical diagnosis and therapy for echolocation effect, cavitation effect, thermal effect, and generation of reactive oxygen species (ROS) with the aid of sonosensitizers. This review summarizes the history, effects, and biomedical applications of US, and US‐assisted cancer therapy is highlighted. The rational combination of US with near‐infrared afterglow nanoparticles, anti‐tumor prodrugs, and stimuli‐responsive nanocarriers, demonstrates the great promise for bioimaging, cancer therapy, and drug delivery, promoting US‐related technology in biomedical diagnosis and therapeutics.

BackgroundFall detection is of great significance in safeguarding human health. By monitoring the motion data, a fall detection system (FDS) can detect a fall accident. Recently, wearable sensors–based FDSs have become the mainstream of research, which can be categorized into threshold-based FDSs using experience, machine learning–based FDSs using manual feature extraction, and deep learning (DL)–based FDSs using automatic feature extraction. However, most FDSs focus on the global information of sensor data, neglecting the fact that different segments of the data contribute variably to fall detection. This shortcoming makes it challenging for FDSs to accurately distinguish between similar human motion patterns of actual falls and fall-like actions, leading to a decrease in detection accuracy. ObjectiveThis study aims to develop and validate a DL framework to accurately detect falls using acceleration and gyroscope data from wearable sensors. We aim to explore the essential contributing features extracted from sensor data to distinguish falls from activities of daily life. The significance of this study lies in reforming the FDS by designing a weighted feature representation using DL methods to effectively differentiate between fall events and fall-like activities. MethodsBased on the 3-axis acceleration and gyroscope data, we proposed a new DL architecture, the dual-stream convolutional neural network self-attention (DSCS) model. Unlike previous studies, the used architecture can extract global feature information from acceleration and gyroscope data. Additionally, we incorporated a self-attention module to assign different weights to the original feature vector, enabling the model to learn the contribution effect of the sensor data and enhance classification accuracy. The proposed model was trained and tested on 2 public data sets: SisFall and MobiFall. In addition, 10 participants were recruited to carry out practical validation of the DSCS model. A total of 1700 trials were performed to test the generalization ability of the model. ResultsThe fall detection accuracy of the DSCS model was 99.32% (recall=99.15%; precision=98.58%) and 99.65% (recall=100%; precision=98.39%) on the test sets of SisFall and MobiFall, respectively. In the ablation experiment, we compared the DSCS model with state-of-the-art machine learning and DL models. On the SisFall data set, the DSCS model achieved the second-best accuracy; on the MobiFall data set, the DSCS model achieved the best accuracy, recall, and precision. In practical validation, the accuracy of the DSCS model was 96.41% (recall=95.12%; specificity=97.55%). ConclusionsThis study demonstrates that the DSCS model can significantly improve the accuracy of fall detection on 2 publicly available data sets and performs robustly in practical validation.

Lamiales, comprising over 23,755 species across 24 families, stands as a highly diverse and prolific plant group, playing a significant role in the cultivation of horticultural, ornamental, and medicinal plant varieties. Whole-genome duplication (WGD) and its subsequent post-polyploid diploidization (PPD) process represent the most drastic type of karyotype evolution, injecting significant potential for promoting the diversity of this lineage. However, polyploidization histories, as well as genome and subgenome fractionation following WGD events in Lamiales species, are still not well investigated. In this study, we constructed a chromosome-level genome assembly of Lindenbergia philippensis (Orobanchaceae) and conducted comparative genomic analyses with 14 other Lamiales species. L. philippensis is positioned closest to the parasitic lineage within Orobanchaceae and has a conserved karyotype. Through a combination of Ks analysis and syntenic depth analysis, we reconstructed and validated polyploidization histories of Lamiales species. Our results indicated that Primulina huaijiensis underwent three rounds of diploidization events following the γ-WGT event, rather than two rounds as reported. Besides, we reconfirmed that most Lamiales species shared a common diploidization event (L-WGD). Subsequently, we constructed the Lamiales Ancestral Karyotype (LAK), comprising 11 proto-chromosomes, and elucidated its evolutionary trajectory, highlighting the highly flexible reshuffling of the Lamiales paleogenome. We identified biased fractionation of subgenomes following the L-WGD event across eight species, and highlighted the positive impacts of non-WGD genes on gene family expansion. This study provides novel genomic resources and insights into polyploidy and karyotype remodeling of Lamiales species, essential for advancing our understanding of species diversification and genome evolution.

Elucidating the absorption and translocation of heavy metal(loid)s by common vegetables across different growth environments and stages is crucial for conducting accurate environmental risk assessments and for associated control. This study investigated temporal variations in the absorption and translocation capacities of pak choi (Brassica rapa L.) for As, Cd, Cr, Cu, Pb, and Zn in polluted soils during the plant growth cycle under greenhouse and open-field cultivation modes. Results showed high root metal(loid) bioconcentration factors and root-to-shoot translocation factors for Cd (0.25 and 1.44, respectively) and Zn (0.26 and 1.01), but low values for As (0.06 and 0.88) and Pb (0.06 and 0.87). The Cd concentration in the aerial edible parts peaked during the early slow growth period, whereas other heavy metal(loid)s peaked during the later stable maturity period. Root bioconcentration and root-to-shoot translocation factors did not significantly differ between cultivation modes. However, greenhouse cultivation exhibited lower average Cd and Zn concentrations in the edible parts and cumulative uptake amounts of most metal(loid)s than open-field cultivation during the typical harvest period spanning days 60 and 90. Short-term transitioning from open-field to greenhouse cultivation may reduce health risks associated with heavy metal(loid) intake via pak choi consumption. These findings facilitate sustainable agricultural practices and food safety management.

Background: MET overexpression represents the most MET aberration in advanced non-small-cell lung cancer (NSCLC). However, except MET exon 14 ( MET ex14) skipping mutation was recognized as a clinical biomarker, the role of MET overexpression as a predictive factor to MET inhibitor is not clear. Objectives: The purpose of the pooled analysis is to explore the safety and efficiency of gumarontinib, a highly selective oral MET inhibitor, in drive-gene negative NSCLC patients with MET overexpression. Design and methods: NSCLC patients with MET overexpression [immunohistochemistry (IHC) ⩾3+ as determined by central laboratory] not carrying epidermal growth factor receptor mutation, MET ex14 skipping mutation or other known drive gene alternations who received Gumarontinib 300 mg QD from two single arm studies were selected and pooled for the analysis. The efficacy [objective response rate (ORR), disease control rate (DCR), duration of response, progression-free survival (PFS) and overall survival (OS)] and safety [treatment emergent adverse event (TEAE), treatment related AE (TRAE) and serious AE (SAE) were assessed. Results: A total of 32 patients with MET overexpression were included in the analysis, including 12 treatment naïve patients who refused or were unsuitable for chemotherapy, and 20 pre-treated patients who received ⩾1 lines of prior systemic anti-tumour therapies. Overall, the ORR was 37.5% [95% confidence interval (CI): 21.1–56.3%], the DCR was 81.3% (95% CI: 63.6–92.8%), median PFS (mPFS) and median OS (mOS) were 6.9 month (95% CI: 3.6–9.7) and 17.0 month (95% CI: 10.3–not evaluable), respectively. The most common AEs were oedema (59.4%), hypoalbuminaemia (40.6%), alanine aminotransferase increased (31.3%). Conclusion: Gumarontinib showed promising antitumour activity in driver-gene negative locally advanced or metastatic NSCLC patients with MET overexpression, which warranted a further clinical trial. Trial registration: ClinicalTrials.gov identifier: NCT03457532; NCT04270591.

Distributed energy resources (DER) are integrated into a microgrid through dc-dc power electronic converters. The bidirectional dc-dc converter regulates charging and discharging operations of ESS. Model predictive control (MPC), is a high-performance control technique for these converters, but it is limited in robustness to parameter mismatch, model uncertainties and sensor measurement noise. Therefore, in this paper, an improved hybrid cascade-parallel extended state observer (CP-ESO) is proposed, for model-free predictive control, to guarantee both robustness to parameter/model uncertainties and measurement noise suppression. A novel structurally-adaptive ESO scheme is also proposed to improve the disturbance rejection of CP-ESO during transient response. These results are supported by analysis and design guidelines for the selection of optimal sub-frequencies. Experimental results, for a bidirectional dc-dc boost converter, validate the effectiveness of the proposed methods against model uncertainties, external disturbances from variable input voltage and load, as well as measurement noise.

IntroductionEnterocytozoon bieneusi, an obligatory intracellular fungus, is prevalent among animals and humans. Due to their close interaction with humans and their extensive regional distribution, brown rats (Rattus norvegicus) are important pathogen reservoirs. To assess the zoonotic transmission potential of E. bieneusi, a molecular investigation was conducted on 817 R. norvegicus from four cities in Heilongjiang Province, China.MethodsA total of 817 R. norvegicus were collected from four cities in Heilongjiang Province, China. The genotyping of E. bieneusi was conducted through PCR amplification of the small subunit ribosomal RNA (SSU rRNA)’s internal transcribed spacer (ITS) segments. Phylogenetic and similarity analyses were used to examine zoonotic potential and genetic characteristics of the E. bieneusi-positive specimens.ResultsAmong the 817 R. norvegicus, the total infection rate was 33.3% (272/817). Seventy-five genotypes were identified, including 14 known genotypes D (n = 167), A (n = 15), HLJ-CP1 (n = 12), WR8 (n = 6), EbpC (n = 2), BEB6 (n = 1), CS-4 (n = 1), CHPM1 (n = 1), Henan-II (n = 1), HNH-22 (n = 1), HNH-25 (n = 1), I (n = 1), JLD-XI (n = 1), SDD5 (n = 1), and 61 novel genotypes designated as SHWR1 (n = 10), SYSWR1 (n = 2), and SHWR2 to SHWR17, SYSWR2 to SYSWR36 and QTHWR1 to QTHWR8 (n = 1, each). Moreover, 10 samples exhibited mixed genotype infections, including D + A (n = 3), D + EbpC (n = 1), D + HLJ-CP1 (n = 1), D + SHWR1 (n = 1), D + SHWR16 (n = 1), D + SHWR17 (n = 1), SDD5 + WR8 (n = 1), and CS-4 + SYSWR36 (n = 1). Phylogenetic analysis grouped the genotypes into three main groups: group 1 (n = 67), group 2 (n = 5), and group 9 (n = 3).DiscussionThe high prevalence and genetic diversity of E. bieneusi in Heilongjiang Province’s R. norvegicus imply that these animals spread the pathogen. The R. norvegicus that E. bieneusi carries can spread zoonotic disease, making it a serious hazard to the local human population. Therefore, it is imperative to raise awareness about the dangers posed by R. norvegicus and implement measures to reduce their population to prevent environmental contamination.

Abstract Organic near‐infrared (NIR) room temperature phosphorescence (RTP) materials become a hot topic in bioimaging and biosensing for the large penetration depth and high signal‐to‐background ratio (SBR). However, it is challenging to achieve persistent NIR phosphorescence for severe nonradiative transitions by energy‐gap law. Herein, a universal system with persistent NIR RTP is built by visible (host) and NIR phosphorescence (guest) materials, which can efficiently suppress the nonradiative transitions by rigid environment of crystalline host materials with good matching, and further promote phosphorescence emission by the additional phosphorescence resonance energy transfer (≈100%) between them. The persistent NIR phosphorescence with ten‐folds enhancement of RTP lifetimes, compared to those of guest luminogens, can be achieved by modulation of aggregated structures of host–guest systems. This work provides a convenient way to largely prolong the phosphorescence lifetimes of various NIR luminogens, promoting their application in afterglow imaging with deeper penetration and higher SBRs.

PurposeNanophthalmos is a congenital ocular structural anomaly that can cause significant visual loss in children. The early diagnosis and then taking appropriate clinical and surgical treatment remains a challenge for many ophthalmologists because of genetic and phenotypic heterogeneity. The objective of this study is to identify the genetic cause of nanophthalmos in the affected families and analyze the clinical phenotype of nanophthalmos with MFRP gene variation (Microphthalmia, isolated; OMIM#611040 and Nanophthalmos 2; OMIM#609549, respectively).MethodsComprehensive ophthalmic examinations were performed on participants to confirm the phenotype. The genotype was identified using whole exome sequencing, and further verified the results among other family members by Sanger sequencing. The normal protein structure was constructed using Alphafold. Mutant proteins were visualized using pymol software. Pathogenicity of identified variant was determined by in silico analysis and the guidelines of American College of Medical Genetics and Genomics (ACMG). The relationship between genetic variants and clinical features was analyzed.ResultsFive nanophthalmos families were autosomal recessive, of which four families carried homozygous variants and one family had compound heterozygous variants in the MFRP gene. Both family one and family three carried the homozygous missense variant c.1486G>A (p.Glu496Lys) in the MFRP gene (Clinvar:SCV005060845), which is a novel variant and evaluated as likely pathogenic according to the ACMG guidelines and in silico analysis. The proband of family one presented papilloedema in both eyes, irregular borders, thickened retinas at the posterior pole, tortuous and dilated retinal vessels, and indistinguishable arteries and veins, while the proband of family three presented uveal effusion syndrome-like changes in the right eye. In families one and 3, despite carrying the same gene variant, the probands had completely different clinical phenotypes. The homozygous nonsense variant c.271C>T (p.Gln91Ter) (Clinvar:SCV005060846) of the MFRP gene was detected in family 2, presenting shallow anterior chamber in both eyes, pigmentation of peripheral retina 360° from the equator to the serrated rim showing a clear demarcation from the normal retina in the form of strips. Family four proband carried the homozygous missense variant c.1411G>A (p.Val471Met) in the MFRP gene (Clinvar:SCV005060847), family five proband carried compound heterozygous missense variants c.1486G>A (p.Glu496Lys) and c.602G>T (p.Arg201Leu) in the MFRP gene (Clinvar:SCV005060848), which is a novel variant and evaluated as likely pathogenic according to the ACMG guidelines and in silico analysis, and they all presented clinically with binocular angle-closure glaucoma, family four also had retinal vein occlusion in the right eye during the follow-up.ConclusionIn this study, pathogenic variants of the MFRP gene were detected in five nanophthalmos families, including two novel variants. It also revealed a distinct phenotypic diversity among five probands harboring variants in the MFRP gene. Our findings extend the phenotype associated with MFRP variants and is helpful for ophthalmologists in early diagnosis and making effective treatment and rehabilitation strategies.

Acetogenic bacteria (acetogens) are a class of microorganisms with conserved Wood-Ljungdahl pathway that can utilize CO and CO2/H2 as carbon source for autotrophic growth and convert these substrates to acetate and ethanol. Acetogens have great potential for the sustainable production of biofuels and bulk biochemicals using C1 gases (CO and CO2) from industrial syngas and waste gases, which play an important role in achieving carbon neutrality. In recent years, with the development and improvement of gene editing methods, the metabolic engineering of acetogens is making rapid progress. With introduction of heterogeneous metabolic pathways, acetogens can improve the production capacity of native products or obtain the ability to synthesize non-native products. This paper reviews the recent application of metabolic engineering in acetogens. In addition, the challenges of metabolic engineering in acetogens are indicated, and strategies to address these challenges are also discussed.

Convergence aspects of nuclear many-body perturbation theory for ground states of closed-shell nuclei are explored using a Brillouin-Wigner formulation with a new vertex function enabling high-order calculations. A general formalism for Hamiltonian partitioning and a convergence criterion for the perturbation series are proposed. Analytical derivations show that with optimal partitioning, the convergence criterion for ground states can always be satisfied. This feature attributes to the variational principle and does not depend on the choice of an internucleon interaction or a many-body basis. Numerical calculations of the ground state energies of He4 and O16 with Daejeon16 and a bare N3LO potential in both harmonic-oscillator and Hartree-Fock bases confirm this finding.

Long non-coding RNAs (lncRNAs) are important factors involved in biological regulatory networks. Accurately predicting lncRNA-protein interactions (LPIs) is vital for clarifying lncRNA’s functions and pathogenic mechanisms. Existing deep learning models have yet to yield satisfactory results in LPI prediction. Recently, graph autoencoders (GAEs) have seen rapid development, excelling in tasks like link prediction and node classification. We employed GAE technology for LPI prediction, devising the FMSRT-LPI model based on path masking and degree regression strategies and thereby achieving satisfactory outcomes. This represents the first known integration of path masking and degree regression strategies into the GAE framework for potential LPI inference. The effectiveness of our FMSRT-LPI model primarily relies on four key aspects. First, within the GAE framework, our model integrates multi-source relationships of lncRNAs and proteins with LPN’s topological data. Second, the implemented masking strategy efficiently identifies LPN’s key paths, reconstructs the network, and reduces the impact of redundant or incorrect data. Third, the integrated degree decoder balances degree and structural information, enhancing node representation. Fourth, the PolyLoss function we introduced is more appropriate for LPI prediction tasks. The results on multiple public datasets further demonstrate our model’s potential in LPI prediction.

Shrews play a crucial role as repositories for diverse pathogens linked to zoonotic infectious diseases. However, the genetic information regarding Cryptosporidium in Chinese shrews remains unexplored. The objectives of this study were twofold: to determine the occurrence rate of Cryptosporidium spp. in wild shrews residing in the southern part of Zhejiang Province, China, and to investigate their genetic characteristics. A total of 282 wild shrews were captured between April and October of 2023. The detection of Cryptosporidium in fecal samples, collected from each animal's rectum, was performed using PCR and sequencing of the partial small subunit of ribosomal RNA (SSU rRNA) gene. The 60-kDa glycoprotein (gp60) gene was utilized to further subtype the positive samples of C. viatorum and C. parvum. All animals were identified as Suncus murinus, and a positive result for Cryptosporidium was obtained in 14.2 % (40/282) of the samples. The following species and genotypes were identified: C. ratti (n = 19), C. parvum (n = 2), C. viatorum (n = 1), Cryptosporidium rat genotype IV (n = 13), and Cryptosporidium skunk genotype (n = 5). Furthermore, the subtypes IIdA15G1 and XVdA3 were detected within C. parvum and C. viatorum, respectively. Molecular evidence indicates that S. murinus is concurrently infected with rodent-adapted and zoonotic species/genotypes, actively contributing to the dissemination of cryptosporidiosis.

Remarkably, e-commerce anchors have become one of the hot careers in the new media era. As a link between goods and consumers, anchors affect the willingness of consumers to purchase, which eventually impacts the sales volume of commodities in the live broadcast. Therefore, the language style of anchors is of vital significance. However, local and foreign research rarely investigates the interaction between the language style of anchors and different product types and the influential mechanism on consumers’ purchase willingness. In light of the SOR theory’s logic and from the viewpoint of consumer perceived value, this research study scrutinizes the interaction between the language styles of different authors (appealing to emotion and appealing to logic) and different types of products (hedonic products and practical products), as well as the effect mechanism on the consumers’ willingness to purchase. Using questionnaire surveys and empirical analysis, this paper intends to analyze the inherent correlation between study variables, in order to extend valuable suggestions for enterprise practice.

For the widespread exposure of toppling deformation phenomena in anti-dip engineering slopes such as hydropower, transportation, and mining, especially deep-seated toppling, these large-scale deep-seated toppling deformations reaching depths of hundreds of meters have become significant geotechnical engineering problems that restrict large-scale engineering construction and require urgent solutions. There are significant differences in the failure characteristics and mechanisms of anti-dip rock slopes under different soft and hard rock conditions. This study, starting from the failure characteristics and mechanisms under different soft and hard conditions of rocks, summarizes two types of toppling deformation: ductile bending deep toppling (DBDT) and brittle fracture shallow toppling (BFST). The UDEC method is used to preliminarily explore the threshold of rock mechanical parameters for these two types of toppling, with 80 MPa (UCS, uniaxial compressive strength) mechanical parameters serving as the preliminary threshold. The results indicate that hard rock undergoes BFST, whereas soft rock undergoes DBDT. The rock mechanical parameters of 100 MPa (UCS) and 20 MPa (UCS) were selected to study the evolution process and mechanism of DBDT and BFST deformations, respectively. Numerical simulation results have innovatively revealed the mechanical behavior characteristics between rock layers during the process of toppling deformation. Because toppling deformation mainly originates from interlayer displacement deformation and intra-layer tensile deformation of rock layers, the interlayer mechanical characteristics are of great significance for understanding the mechanism of toppling deformation. This research can provide a theoretical basis for the stability assessment and development utilization of anti-dip rock slopes and toppled slopes.

Objective: To explore the clinical features and prognosis of patients with neuromyelitis optica spectrum disorder (NMOSD) initially presenting with acute brainstem symptoms. Methods: The clinical data of NMOSD patients admitted to two medical centers were collected. The clinical characteristics, laboratory data, neuroimaging features and prognoses of patients with NMOSD with acute brainstem manifestations as initial symptoms (NMOSD-BSMIS) were analyzed. The clinical features and prognosis of patients with NMOSD-BSMIS and patients with NMOSD with other manifestations as initial symptoms (NMOSD-OMIS) were compared. Results: Fifty-two patients (18.37 %, 52/283) initially presented with acute brainstem symptoms. Intractable nausea, vomiting or hiccups, diplopia, vertigo, headache, and facial hypoesthesia were the initial symptoms in most of the patients. The percentage of patients who were positive for serum aquaporin 4 (AQP4)-IgG antibodies was 81.63 % (40/49). MRI revealed that the lesions were usually located in the postrema, dorsal medulla oblongata, pons and other areas around the fourth ventricle. The early-stage misdiagnosis rate was 46.15 %. Compared with those in the non-misdiagnosed group, the age of onset of patients in the NMOSD-BSMIS group was older, and the proportion of patients admitted to the neurology department as the first department was lower in the misdiagnosed group. The annual relapse rate of patients who underwent NMOSD-BSMIS was significantly greater than that of patients who underwent NMOSD-OMIS (P

During the preparation of asphalt mixtures, styrene-butadiene rubber (SBR) polymers are susceptible to thermal decomposition, which can significantly impair the binder’s low-temperature performance. This study explores the potential of combining warming agents with waste materials to enhance the low-temperature properties and aging resistance of the binder. Specifically, it examines the synergistic impact of Sasobit/recycled engine oil (Sasobit/REO) composites on the rheological and physical attributes of styrene-butadiene rubber asphalt binder (SBRAB). Utilizing fluorescence microscopy (FM), bending beam rheometer (BBR), and dynamic shear rheometer (DSR), the study assesses the aging resistance and modification mechanisms of Sasobit/REO on SBRAB. The findings indicate that the incorporation of Sasobit/REO composites more effectively reduces the mix preparation temperature than either component alone. The preparation of Sasobit/REO warm mix asphalt mixtures is feasible at temperatures 20°C lower than those required for traditional hot mixtures. These composites also enhance the performance of SBRAB at both high and low temperatures, counteracting the adverse effects associated with the individual use of Sasobit or REO. This reduced short-term aging temperature is beneficial in lessening the negative impact of high temperatures on SBRAB’s performance. Moreover, the addition of Sasobit/REO composites significantly improves the thermal cracking resistance of SBRAB mixtures. The study also demonstrates that Sasobit/REO enhances the short-term and long-term aging resistance of SBRAB, paving the way for the broader application of this novel warm mix additive in the asphalt industry.

Research on the positive impacts of uncertainty has primarily focused on promotional activities, with little research in other situations. This study applied the concept of uncertainty to the context of experience consumption, Discovering there is certainty of experience and uncertainty of experience in the context of consumption, The purpose is to study the differences in the mechanism of action of different types of consumer experience. In studyⅠ, 239 valid questionnaires on the mobile app consumption experiences were collected and their data were analyzed using structural equation modeling (SEM). Study 2 collected 160 valid questionnaires on consumer experience in physical stores and analyzed the questionnaire data using partial least squares (PLS-SEM). study finding in the certainty of experience context, standardized interaction relies on product interaction and scene interaction to transmit experience material information, and reduce consumers' commodity service perception uncertainty, resulting in a satisfaction experience; in the uncertainty of experience context, personalized interaction relies on user-enterprise interaction and user-to-user interaction to unleash the subjectivity and creativity of experience participants, and increase consumers’ experience process perception uncertainty, resulting in the realization a surprise experience. The research findings provide important practical guidance for enterprises to establish differentiated experience strategies and gain long-term competitive advantages.

Zn2P2O7, a representative material in the A2P2O7 family, exhibits negative thermal expansion (NTE) and possesses a remarkable negative linear expansion coefficient. Here we employ variable temperature and high-pressure Raman spectroscopy to investigate the phonon anomalies arising from the α- to β-phase transition in Zn2P2O7. Combing with the refinement results of our X-ray diffraction (XRD) experiment, we have identified the specific variations of the bond lengths, bond angles and the polyhedral distortion indexes that result in the phonon anomalies. Some certain phonons, whose energy decreases with increasing pressure, have been demonstrated to give rise to negative Grüneisen parameters that can characterize phonon anharmonicity and lead to lower thermal expansion in the α-phase of Zn2P2O7 compared to the β-phase. These results provide new insight into the relationship between lattice deformation and phonon anomalies during the structural phase transition in the NTE material Zn2P2O7.

Core 1 β 1,3-galactosyltransferase 1 (C1GALT1) acts as an important glycosyltransferase in the occurrence and development of tumor glycosylation. However, the regulatory mechanisms of C1GALT1 in thyroid cancer (TC) is still unclear. In this study, we discovered that the expression level of C1GALT1 was significantly increased in thyroid adenocarcinoma tissues and cell lines (p

Summary: Camellia oleifera is an economically and medicinally valuable oilseed crop. Honeybee, the most abundant pollinator, rarely visits C. oleifera because of the toxic sugars in the nectar and pollen. These toxic sugars cannot be fully digested by honeybees and inhibit the process of synthesizing trehalose in honeybees. C. oleifera exhibits self-incompatibility, and its pollination heavily depends on Andrena camellia. However, the mechanism by which A. camellia digests toxic sugars in C. oleifera nectar and pollen remains unknown. Consequently, we identified and validated four single-copy genes (α-N-acetyl galactosamine-like, galactokinase, galactose-1-phosphate uridyltransferase, and UDP-galactose-4′-epimerase, abbreviated as NAGA-like, GALK, GALT, and GALE) essential for detoxifying toxic sugars in vitro. Then, we cloned the four genes into Escherichia coli, and expressed enzyme successfully degraded the toxic sugars. The phylogeny suggests that the genes were conserved and functionally diverged among the evolution. These results provide novel insights into pollinator detoxification during co-evolution.