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Abstract Total proctocolectomy with ileal pouch anal anastomosis is the standard of care for patients with severe ulcerative colitis. We generated a cell-type-resolved transcriptional and epigenetic atlas of ileal pouches using scRNA-seq and scATAC-seq data from paired biopsy samples of the ileal pouch and the ileal segment above the pouch (pre-pouch) from patients (male=4, female=2), and paired biopsies of the terminal ileum and ascending colon from healthy individuals (male=3, female=3) serving as reference. Our study finds an additional population of absorptive and secretory epithelial cells within the pouch but not the pre-pouch. These pouch-specific enterocytes express a subset of colon-specific genes, including CEACAM5 and CD24. However, compared to normal colonocytes, expression of these genes is lower, and these enterocytes also express inflammatory and secretory genes while maintaining expression of some ileal-specific genes. This cell-type-resolved transcriptomic and epigenetic atlas of the ileal pouch establishes a reference for investigating pouch physiology and pathology.

Abstract The Sc2.0 global consortium to design and construct a synthetic genome based on the Saccharomyces cerevisiae genome commenced in 2006, comprising 16 synthetic chromosomes and a new-to-nature tRNA neochromosome. In this paper we describe assembly and debugging of the 902,994-bp synthetic Saccharomyces cerevisiae chromosome synXVI of the Sc2.0 project. Application of the CRISPR D-BUGS protocol identified defective loci, which were modified to improve sporulation and recover wild-type like growth when grown on glycerol as a sole carbon source when grown at 37˚C. LoxPsym sites inserted downstream of dubious open reading frames impacted the 5’ UTR of genes required for optimal growth and were identified as a systematic cause of defective growth. Based on lessons learned from analysis of Sc2.0 defects and synXVI, an in-silico redesign of the synXVI chromosome was performed, which can be used as a blueprint for future synthetic yeast genome designs. The in-silico redesign of synXVI includes reduced PCR tag frequency, modified chunk and megachunk termini, and adjustments to allocation of loxPsym sites and TAA stop codons to dubious ORFs. This redesign provides a roadmap into applications of Sc2.0 strategies in non-yeast organisms.

Abstract Human papillomaviruses, particularly high-risk human papillomaviruses, have been universally considered to be associated with the oncogenesis and progression of various cancers. The genome of human papillomaviruses is circular, double-stranded DNA that encodes early and late proteins. Each of the proteins is of crucial significance in infecting the epithelium of host cells persistently and supporting viral genome integrating into host cells. Notably, E6 and E7 proteins, classified as oncoproteins, trigger the incidence of cancers by fostering cell proliferation, hindering apoptosis, evading immune surveillance, promoting cell invasion, and disrupting the balance of cellular metabolism. Therefore, targeting human papillomaviruses and decoding molecular mechanisms by which human papillomaviruses drive carcinogenesis are of great necessity to better treat human papillomaviruses-related cancers. Human papillomaviruses have been applied clinically to different facets of human papillomavirus-related cancers, including prevention, screening, diagnosis, treatment, and prognosis. Several types of prophylactic vaccines have been publicly utilized worldwide and have greatly decreased the occurrence of human papillomavirus-related cancers, which have benefited numerous people. Although various therapeutic vaccines have been developed and tested clinically, none of them have been officially approved to date. Enhancing the efficacy of vaccines and searching for innovative technologies targeting human papillomaviruses remain critical challenges that warrant continuous research and attention in the future.

Abstract Background Recent advancements in contemporary therapeutic approaches have increased the survival rates of lung cancer patients; however, the long-term benefits remain constrained, underscoring the pressing need for novel biomarkers. Surfactant-associated 3 (SFTA3), a long non-coding RNA predominantly expressed in normal lung epithelial cells, plays a crucial role in lung development. Nevertheless, its function in lung adenocarcinoma (LUAD) remains inadequately understood. Methods Single-cell RNA sequencing data were utilized to identify novel cancer cell-intrinsic gene signatures associated with the progression of LUAD, and their roles in LUAD were comprehensively analyzed. Serum samples were collected to quantify the expression levels of SFTA3 in LUAD patients. Furthermore, a series of biological experiments, including cell viability assays, scratch wound healing assays, and colony formation assays, were conducted to demonstrate the tumor-suppressive effects of SFTA3. RNA sequencing was performed to elucidate the molecular mechanisms underlying the role of SFTA3 in lung cancer cells. Results We constructed a prognostic model comprising eight genes: ALDOA, ATP5MD, SERPINH1, SFTA3, SLK, U2SURP, SCGB1A1, and SCGB1A3. The model effectively stratified patients into high- and low-risk categories, revealing that low-risk patients experienced superior clinical outcomes, exhibited an immunologically hot tumor microenvironment (TME), and had a greater probability of responding to immunotherapy. In contrast, the high-risk group exhibited a cold TME and may benefit more from chemotherapy. Furthermore, our study revealed that a progressive decrease in SFTA3 expression in cancer cells was correlated with tumor advancement. Notably, the serum levels of SFTA3 significantly decreased in patients with LUAD, suggesting its potential utility in liquid biopsy for LUAD diagnosis. Additionally, the knockdown of SFTA3 enhances the proliferation and migration of lung cancer cells, whereas its overexpression inhibits these phenotypes. The epithelial-mesenchymal transition pathway was significantly enriched following SFTA3 silencing, suggesting that SFTA3 may impact tumor progression by modulating this process. We also identified key transcription factors and epigenetic mechanisms implicated in the downregulation of SFTA3 in LUAD. Conclusion We developed a robust prognostic model and identified SFTA3 as a novel biomarker with potential applications in the diagnosis, prognosis, and personalized treatment of LUAD. Additionally, our findings offer new insights into the mechanisms underlying LUAD tumorigenesis and immune evasion.

Abstract Effective abatement of air-pollution-induced health damages requires a comprehensive understanding of the changing roles of individual sources and cross-regional transport. Here, we estimate premature mortality attributable to specific source categories, precursor species, and regions within mainland China. We find that the marginal national premature deaths, dominated by PM2.5 exposure, have declined from 151,842 per 10% growth of emissions in 2013 to 111,271 in 2020, and would further to 54,293 in 2035 following a carbon peaking and carbon neutrality pathway. The impacts of certain species-category combinations have grown including NOX from industrial combustion and off-road traffic. The proportions of cross-provincial to marginal health burden have remained stable at around 50%. Provinces with net exporting of premature deaths were intensively located in the north of China while those with net importing were in the south. Our findings highlight the need for a location-precursor/sector-specific strategy of emission controls in China’s public health regulatory framework.

Abstract In order to investigate the influence of shear on contact characteristics and fluid flow evolution of rough rock fractures, a series of shear-flow tests were carried out by numerical experiments. Firstly, a sandstone specimen with a rough fracture was made in the laboratory, and the numerical model of the fracture was reconstructed in FLAC3D software. Experiments were conducted to investigate the depth of penetration of the fracture under different normal stress (1, 3, and 5 MPa) and shear displacement (2, 4, 6, 8, and 10 mm). By establishing the relationship between the shear direction and the apparent inclination of the fracture asperity, the effects on the asperity contact characteristics and seepage properties are explored. The results of the study indicated that the larger the normal stress the larger the surface contact section and the smaller the aperture, showing the opposite trend with increasing shear displacement. Positive apparent inclination distribution can effectively predict the location of shear damage during the shear process. Negative apparent dip implies that those regions increase permeability after shear, and decrease with increasing crack opening. Fracture seepage shows obvious nonlinear characteristics, where the nonlinear coefficients are 5–6 orders of magnitude larger than the linear coefficients. The critical Reynolds number Rec is used to distinguish the linear and nonlinear categories of fluid flow, and the calculated results show that the range of Rec is between 0.0081 and 0.11.3, and the Rec increases with shear displacement and decreases with normal stress.

Abstract Background Clinical reception training plays a crucial role in developing undergraduates’ clinical thinking and competence. The study aimed to evaluate the effectiveness of clinical reception training conducted by standard patients (SPs) and dental simulators among undergraduate students. Materials and methods In the first week of the internship, sixty-five 5th-year undergraduate students were divided into two groups: SP group, which received traditional theoretical training along with clinical reception training, and control group that only received traditional theoretical training. After 2 weeks and 8 weeks of training, all students were assessed with real patients by experienced prosthodontists using Mini-CEX assessment score sheets. Statistical analysis was performed using independent-samples T test or repeated-measures ANOVA (P

Abstract Gliomas are the most common tumors of the central nervous system, with glioblastoma (GBM) being particularly aggressive and fatal. Current treatments for GBM, including surgery and chemotherapy, are limited by tumor aggressiveness and the blood-brain barrier. Therefore, understanding the molecular mechanisms driving GBM growth is essential. Mitochondria, key players in cellular energy production, have been implicated in cancer development. In this study, we investigated the expression of mitochondrial transcription elongation factor (TEFM) in gliomas and its potential role in tumor progression. Analysis of data from The Cancer Genome Atlas (TCGA) revealed that TEFM transcript levels were significantly higher in glioma tissues compared to adjacent normal tissues. High TEFM expression was associated with poor survival outcomes in glioma patients. Furthermore, TEFM was notably upregulated in glioma tissue and in primary glioma cells derived from local patients, while its expression was relatively low in normal tissues and astrocytes. Silencing or knockout of TEFM significantly inhibited glioma cell growth, proliferation, clonogenicity, migration, and invasion, while inducing apoptosis and activating caspases. In contrast, ectopic overexpression of TEFM promoted tumorigenic activity, enhancing the malignant behavior of glioma cells. Co-expression analysis identified a strong correlation between TEFM and the epithelial-mesenchymal transition (EMT) pathway in gliomas. Notably, the expression of EMT markers, such as N-cadherin and Vimentin, decreased upon TEFM knockdown or knockout. Additionally, TEFM depletion impaired mitochondrial function, disrupting the mitochondrial respiratory chain in glioma cells. In vivo experiments demonstrated that TEFM knockout effectively suppressed the growth of subcutaneous glioma xenografts in nude mice. Collectively, these findings highlight the critical role of TEFM in GBM growth and invasion, suggesting that it could serve as a promising therapeutic target for glioma treatment. Graphical Abstract

Abstract Bacillus subtilis has been widely used as a biological control agent in agricultural production. Environmental strains of B. subtilis are an important source of biological control agents. However, due to its low genetic transformation efficiency, the genetic manipulation of the environmental and nondomesticated strains is challenging. In this study, the impact of competent cell preparation, pulse electroporation, and recovery culture on the electroporation efficiency of B. subtilis GLB191 was assessed utilizing response surface methodology. Results indicated that the concentration of glycine, DL-threonine, and Tween 80 used in a cell wall weakening solution during competent cell preparation, and the voltage applied during pulse electroporation were the primary factors affecting electroporation efficiency. Optimization of these factors led to nearly a three-fold increase (reaching 74.00 ± 5.10 CFU/µg DNA) in electroporation efficiency. The elimination of dam and dcm modifications to mitigate the influence of host restriction-modification systems was integrated to further increase the electroporation efficacy. An electroporation efficiency for replicative plasmids of 1.96 ± 0.05 × 106 CFU/µg DNA was achieved using the optimized strategy. Utilizing this improved methodology, the temperature-sensitive plasmid pJOE8899 was efficiently transformed into B. subtilis GLB191, resulting in a markerless knockout of pdeH. The optimized transformation strategy significantly enhances the efficiency of markerless genome editing of nondomesticated B. subtilis, offering the potential for future interpretation of their modes of action, which is critical for the development of the nondomesticated B. subtilis strains.

The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from ∼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.

Abstract Airborne warning and control systems (AWACS) serve as critical command and control centres in air combat operations, making them prime targets for strategic attacks. These enemy attacks typically rely on the accurate determination of AWACS combat positions using different direction‐finding devices. In particular, passive monopulse angle measurement systems locate AWACS by measuring the angles of signals emitted by AWACS radiation sources, thus rendering them vulnerable to attacks. Given the criticality of the airborne radars of AWACS in battle command and control operations, they must function continuously to monitor air and sea targets. Hence, AWACS cannot effectively evade electronic reconnaissance systems through tactics such as radar shutdown. To explore alternative measures, the authors investigate the deception mechanisms of an integrated frequency diverse array AWACS (FDA‒AWACS) against passive monopulse angle measurements. Using an established FDA signal model, the principles underlying two common monopulse angle measurement methods are first outlined. Subsequently, the angle estimation formulae typically used by these monopulse angle measurement systems to interpret received FDA radiation signals are derived. Additionally, the transmit beampatterns, amplitude patterns, and angle measurement deception capabilities of several typical FDAs are examined. Simulation results indicate that the FDA‒AWACS can theoretically deceive passive monopulse angle measurement systems to a certain extent. However, one‐dimensional uniform linear FDAs and other arrays using sinusoidal frequency offsets exhibit limited deception abilities. In contrast, arrays utilising cubic and quartic frequency offset achieve angle measurement errors exceeding 2° in far‐field scenarios.

Abstract Background Spaghetti knotting technology is an emerging technique that can reduce the visual field restriction of the operator in laparo-endoscopic single site (LESS) surgery. Multi-directional stitching technology has been proved to improve the accuracy of suturing in clinical application of LESS surgery. Therefore, we conducted a study to evaluate the teaching efficacy and the operation workload of spaghetti knotting technology and conventional knotting technology in LESS suture teaching based on the multi-directional stitching technology. Methods We selected forty junior residents to learn the skill of knot tying with single-hole laparoscopic simulators. The forty students were randomly and equally divided into control group and experimental group. The control group was trained by the conventional knotting method, and the experimental group was trained by the spaghetti knotting technology. The grades were calculated before and after the training program, including operation score of suturing time, trhead length, needle insertion accuracy, knotting stability, tissue integrity, tissue tightness and the cognitive workload score of mental, physical and temporal demands, performance, effort and frustration. Results There was no significant difference between two groups before training. After training, knotting skills and workload were significantly improved. There were significant differences between the two groups in knotting time (p = 0.001), thread length (p = 0.01), and tissue integrity(p = 0.003). The experiment group took less time, left longer thread and had higher tissue integrity. The workload of the experiment group was also accurately reduced. However, there was no significant difference between the two groups in needle insertion accuracy(p = 0.560), knotting stability(p = 0.059), and tissue tightness(p = 0.731). Conclusion In LESS suture teaching based on the multi-directional stitching technology, the training of spaghetti knotting techniques significantly improved students’ learning efficacy and reduced their workload compared to training conventional knotting techniques. It suggested the combination of spaghetti knotting and multi-directional stitching technology could be a practicable method for laparoscopic skills teaching and a feasible clinical application value on spaghetti knotting technology in LESS surgery.

Abstract Objectives To investigate the feasibility and effectiveness of a deep learning (DL) super-resolution (SR) ultrasound image reconstruction model for predicting cervical lymph node status in patients with papillary thyroid carcinoma(PTC). Methods In this retrospective study, researchers recruited 544 patients with PTC and randomly assigned them to training and test sets. SR ultrasound images were acquired using SR technology to improve image resolution, and artificial features and DL features were extracted from the original (OR) and SR images, respectively, to construct a ML, DL model. The best model was selected and aggregated with clinical parameters to construct the nomogram. The performance of the model is evaluated by ROC curves, calibration curves and decision curves. Results In distinguishing the presence or absence of metastatic lymph nodes, the predictive performance of the SR_ResNet 101 and SR_SVM models based on SR outperformed those based on OR. In the test set, SR_SVM AUC was 0.878 (95% CI 0.8203–0.9358), accuracy 0.854, while OR_SVM AUC was 0.822 (95% CI 0.7500–0.8937), accuracy 0.665. SR_ResNet 101 AUC was 0.799 (95% CI 0.7175–0.8806), accuracy 0.793, and OR_ResNet101 AUC was 0.751 (95% CI 0.6620–0.8401), accuracy 0.713. Subsequently, Nomogram_A and Nomogram_B were constructed by integrating the SR_SVM model and SR_ResNet 101 model, respectively, with clinical parameters, while Nomogram_C was constructed solely based on clinical indicators. In the test set, Nomogram_A demonstrated the best performance with an AUC of 0.930 (95% CI 0.8913–0.9682) and accuracy was 0.829. Nomogram_B AUC 0.868 (95% CI 0.8102–0.9261) and accuracy was 0.829, while Nomogram_C AUC 0.880 (95% CI 0.8257–0.9349) and accuracy was 0.787. The DeLong test revealed that the diagnostic performance of Nomogram_A based on SR_SVM was significantly higher than that of Nomogram_B, Nomogram_C, and the level of Radiologist (P

Abstract Dielectric elastomers, used as driver modules, require high power density to enable fast movement and efficient work of soft robots. Polyacrylate elastomers usually suffer from low power density under low electric fields due to limited response frequency. Here, we propose a bimodal network polyacrylate dielectric elastomer which breaks the intrinsic coupling relationship between dielectric and mechanical properties, featuring relatively high dielectric constant, low Young’s modulus, and wide driving frequency bandwidth (~200 Hz) like silicones. Therefore, an ultrahigh power density (154 W kg−1@20 MV m−1, 200 Hz) is realized at low electric field and high resonance frequency, 75 times greater than at 10 Hz. Further, a rotary motor is developed, reaching an impressive speed of 1245 rpm at 19.6 MV m−1 and 125 Hz, surpassing previous acrylate-based motors and entering the high-speed domain of silicone-based motors. These findings offer a versatile strategy to fabricate high-power-density dielectric elastomers for low-electric-field soft actuators.

Abstract RNA structure constitutes a new layer of gene regulatory mechanisms. RNA binding proteins can modulate RNA secondary structures, thus participating in post-transcriptional regulation. The DEAH-box helicase 36 (DHX36) is known to bind and unwind RNA G-quadruplex (rG4) structure but the transcriptome-wide RNA structure remodeling induced by DHX36 binding and the impact on RNA fate remain poorly understood. Here, we investigate the RNA structurome alteration induced by DHX36 depletion. Our findings reveal that DHX36 binding induces structural remodeling not only at the localized binding sites but also on the entire mRNA transcript most pronounced in 3’UTR regions. DHX36 binding increases structural accessibility at 3’UTRs which is correlated with decreased post-transcriptional mRNA abundance. Further analyses and experiments uncover that DHX36 binding sites are enriched for N6-methyladenosine (m6A) modification and YTHDF1 binding; and DHX36 induced structural changes may facilitate YTHDF1 binding to m6A sites leading to RNA degradation. Altogether, our findings uncover the structural remodeling effect of DHX36 binding and its impact on RNA abundance through regulating m6A dependent YTHDF1 binding.

Abstract Neurexin, a molecule associated with autism spectrum disorders, is thought to function mainly in neurons. Recently, it was reported that Neurexin is also present in muscle, but the role of Neurexin in muscle is still poorly understood. Here, we demonstrate that the overexpression of Neurexin in muscles effectively restored the locomotor function of Drosophila neurexin mutants, while rescuing effects are observed within the nervous. Notably, the defects in muscle structure and function caused by Neurexin deficiency were similar to those caused by mutations in dystroglycan, a gene associated with progressive muscular dystrophy. The absence of Neurexin leads to muscle attachment defects, emphasizing the essential role of Neurexin in muscle integrity. Furthermore, Neurexin deficiency reduces Dystroglycan glycosylation on the cell surface, which is crucial for maintaining proper muscle structure and function. Finally, Neurexin guides Dystroglycan to the glycosyltransferase complex through interactions with Rotated Abdomen, a homolog of mammalian POMT1. Our findings reveal that Neurexin mediates muscle development and function through Dystroglycan glycosylation, suggesting a potential association between autism spectrum disorders and muscular dystrophy.

ObjectiveTo analyze the spatiotemporal clustering of anthrax cases in the Ningxia Hui Autonomous Region from 2019 to 2022 and to perform molecular typing of 14 strains of Bacillus anthracis (B. anthracis) isolated during the same period. MethodsData on anthrax cases reported in Ningxia Hui Autonomous Region (Ningxia) from 2019 to 2022 were collected, and spatiotemporal cluster analysis was performed using SaTScan software with districts and counties as units. A total of 14 strains of B. anthracis isolated from local anthrax cases from 2019 to 2021 were subjected to molecular typing analysis using canonical single nucleotide polymorphisms (CanSNPs), twenty-five marker multilocus variable number tandem repeat analysis (MLVA-25), and single nucleotide repeat (SNR-4) methods. ResultsA total of 80 anthrax cases, all of which were cutaneous anthrax, were reported in Ningxia during the 3-year period. SaTScan spatiotemporal cluster analysis revealed a spatiotemporal cluster in north-central Ningxia from 2021 to 2022, with a primary cluster in Yongning county [P < 0.01, relative risk (RR) = 13.83] and secondary clusters in Lingwu city and Litong district (P = 0.022, RR = 3.47). The genetic relationships of the 14 B. anthracis strains isolated during the same period were defined as: A.Br 001/002 subgroup, 6 different MLVA genotypes within A3.b gene cluster, of which 3 common genotypes were defined as 2, 3, and 5 PHANA genotypes, respectively, by SNR-4 analysis; SNR-4 analysis showed 12 SNR genotypes. ConclusionThe incidence of anthrax in Ningxia showed an increasing trend from 2019 to 2022. One of the reasons for the formation of spatiotemporal clusters of anthrax in 2021 – 2022 may be the formation and development of natural foci. Molecular typing revealed that the genetic relationship of the strains isolated in Ningxia from 2019 to 2022 was relatively homogeneous, with abundant genetic diversity within the same genetic relationship.

ObjectiveTo evaluate the associations of meteorological factors and ambient air pollutants with the incidence of mumps in Ningxia Hui Autonomous Region, and to provide a reference for the development of early warning and response systems for mumps epidemic. MethodsData on the daily number of mumps cases in Ningxia Hui Autonomous Region from 2015 to 2019 were obtained from the Notifiable Infectious Disease Surveillance System of the region, and data on meteorological factors (daily mean temperature/relative humidity/atmospheric pressure/wind speed) and air pollutants (daily concentrations of ozone, [O3], sulfur dioxide [SO2], carbon monoxide [CO], nitrogen dioxide [NO2], and particulate matter with aerodynamic diameter < 2.5/10 mum [PM2.5/PM10]) for the same period were obtained from the National Meteorological Science Data Center. A boosted regression tree (BRT) model was used to determine the optimal lag of meteorological factors and air pollutants that best explained mumps cases and to evaluate the associations of meteorological factors and air pollutants with the daily number of mumps cases in the region. ResultsA total of 6 660 new cases of mumps were reported in the region during the period, including 3 936 males (59.1%) and 2 724 females (40.9%); 2 230 (33.5%) were aged less than 4 years, 3 537 (53.1%) were aged 4 – 15 years and 893 (13.4%) were aged > 15 years. The BRT model validation results showed that the model had the largest area under the receiver operating characteristic curve (AUC) value of 0.915 for the training set and 0.717 for the test set at a lag of 7 days, with a standard error of 0.027, indicating that in the region, meteorological factors and air pollutants one week prior had the greatest explanatory power for changes in the number of new mumps cases. BRT model analysis showed that daily mean temperature had the greatest relative importance on mumps incidence at 26.36%, followed by daily mean relative humidity at 13.90%. Daily mean temperatures of – 3 °C to 23 °C and daily mean relative humidity > 40% were risk factors for mumps incidence. Higher daily mean barometric pressure and daily mean wind speed had an inhibitory effect on mumps incidence. Lower ambient O3 concentrations promoted mumps incidence; ambient SO2 concentrations < 100 μg/m3 promoted mumps incidence, whereas SO2 concentrations ≥ 100 μg/m3 had an inhibitory effect. Lower concentrations of CO, NO2, PM2.5, and PM10 all promoted mumps incidence. ConclusionDaily mean temperature/relative humidity/air pressure/wind speed, as well as ambient air O3, SO2, CO, NO2, PM2.5, and PM10, all significantly contributed to the incidence of mumps in Ningxia Hui Autonomous Region.

Abstract To determine the characteristics of posterior precortical vitreous pockets (PPVPs) and to observe vitreous changes in myopic eyes by swept-source optical coherence tomography (SS-OCT) and en face imaging in a cohort of the Chinese Han population. This was a cross-sectional study. Volunteers (235 participants, 374 eyes) received an SS-OCT examination. The heights and widths of the PPVPs were measured by SS-OCT. The area of the PPVPs was measured on en face images. The relationships between PPVP size and sex, age, axial length (AL) and spherical equivalent (SE) were evaluated. The mean width and height were 6711.64 ± 1241.87 μm and 662.47 ± 326.39 μm, respectively. The area of the PPVPs was 30.296 ± 9.114 mm2. Boat-shaped, oval, and hook-shaped PPVPs were observed in 73.26%, 21.12%, and 5.62% of all eyes, respectively; 73.53% of all PPVPs had channels communicating with Cloquet’s tubes. There was a significant difference in the PPVP width among the participates over and under 50 years old (t = -2.508, P = 0.031). Age had a positive correlation with the PPVP width (r = 0.53, P = 0.001). The PPVP height showed significant differences among the different myopia groups (F = 3.618, P = 0.013). SE had a negative correlation with the PPVP height (r = -0.176, P = 0.001). However, there were no correlations between the AL and the width, height or area of the PPVPs (P = 0.117; P = 0.334; P = 0.057, respectively). Age and myopia affect the size of PPVPs. SS-OCT greatly facilitates visualization of the complex structure of the vitreous.

TNM(Ti–43Al–4Nb–1Mo–0.1B) titanium aluminum alloy has low density, excellent mechanical properties at high temperatures, and good deformation ability at high temperatures and is applied as a new-generation aeroengine low-pressure turbine blade material. Its long-term service temperature can reach approximately 750 ℃. In this paper, a TiAl alloy with a nominal composition of Ti–43Al–4Nb–1Mo–0.1B (atom fraction, %) was prepared using the vacuum induction levitation melting method. Oxygenation samples with dimensions of 10 mm×10 mm×5 mm were fabricated using electrical discharge wire cutting. After sandpaper polishing, the surface of the samples was selected for oxidation testing in air at two different temperatures of 700 ℃ and 760 ℃ for nine oxidation time points of 1–200 h using a muffle furnace. A systematic investigation was performed on the oxidation behavior of the TNM alloy at different temperatures and time exposures by characterizing its surface morphology and surface and cross-sectional oxide composition using scanning electron microscopy, energy dispersive spectroscopy, and X-ray photoelectron spectroscopy. Results revealed that at 700 ℃ and 760 ℃, the TNM alloy displays complete oxidation resistance and antioxidation levels and the weight gain rate of the sample at 760 ℃ is 0.1956 g·m−2·h−1, which is much higher than that at 700 ℃. At 700 ℃, the TNM alloy initially forms TiO2 during the early stage of oxidation, followed by a gradual increase in Al2O3 until it covers the entire sample. After 200 h of oxidation, the predominant surface oxides on the alloy were Al2O3 with small amounts of MoO2 and MoO3, which exhibited excellent oxidation resistance. At 760 ℃, the alloy forms unstable oxide compounds of Al and Ti during the initial stage of oxidation, and the growth rate of TiO2 is faster, destroying the continuous and dense Al2O3 layer on the surface and making the matrix more easily oxidized. After 200 h of oxidation, the predominant oxide on the surface is mainly TiO2 with small amounts of MoO2, MoO3, and other molybdenum oxides, with the oxidized surface of the TNM alloy exhibiting a typical multilayer structure of a TiO2 layer (outermost layer) + an Al2O3 layer + a mixed layer (consisting of Ti, O, Nb, Mo) + substrate. Furthermore, the thickness of the oxide layer is significantly greater at 760 ℃ than at 700 ℃.

Abstract Arthroscopic capsular release is a most well-known technique with favorable outcomes for frozen shoulder. However, considering the surgical trauma and the improvement of multisite injection, we design a study to compare the pain relief and safety of multisite injection (MI) versus arthroscopic capsular release (ACR) for frozen shoulder. A total of 80 patients with unilater al frozen shoulder were enrolled in this study. Group RBT (n = 40) received multisite injection (0.5% lidocaine and triamcinolone acetonide, once a week, no more than 2 injections), while Group ACR received arthroscopic capsular release. The following parameters were employed to compare: visual analog scale (VAS), range of motion (ROM), the Disability of Arm, Hand, and Shoulder (DASH) score and Oxford shoulder score (OSS). Side effects were also recorded. The VAS, ROM, DASH and OSS all improved significantly (P

Abstract Salmonella Enteritidis is a major foodborne pathogen throughout the world and the increase in antibiotic resistance of Salmonella poses a significant threat to public safety. Natural nanobodies exhibit high affinity, thermal stability, ease of production, and notably higher diversity, making them widely applicable for the treatment of viral and bacterial infections. Recombinant expression using Lactococcus lactis leverages both acid resistance and mucosal colonization properties of these bacteria, allowing the effective expression of exogenous proteins for therapeutic effects. In this study, nine specific nanobodies against the flagellar protein FliC were identified and expressed. In vitro experiments demonstrated that FliC-Nb-76 effectively inhibited the motility of S. Enteritidis and inhibited its adhesion to and invasion of HIEC-6, RAW264.7, and chicken intestinal epithelial cells. Additionally, a recombinant L. lactis strain secreting the nanobody, L. lactis-Nb76, was obtained. Animal experiments confirmed that it could significantly reduce the mortality rates of chickens infected with S. Enteritidis, together with alleviating the inflammatory response caused by the pathogen. These results provide a novel strategy for the treatment of antibiotic-resistant S. Enteritidis infection in the intestinal tract. Graphical Abstract

Abstract Background Leaves are important sites for photosynthesis and can convert inorganic substances into organic matter. Photosynthetic performance is an important factor affecting crop yield. Leaf colour is closely related to photosynthesis, and leaf colour mutants are considered an ideal material for studying photosynthesis. Results We obtained a yellow-green leaf mutant jym165, using ethyl methane sulfonate (EMS) mutagenesis. Physiological and biochemical analyses indicated that the contents of chlorophyll a, chlorophyll b, carotenoids, and total chlorophyll in the jym165 mutant decreased significantly compared with those in Jiyu47 (JY47). The abnormal chloroplast development of jym165 led to a decrease in net photosynthetic rate and starch content compared with that of JY47. However, quality traits analysis showed that the sum of oil and protein contents in jym165 was higher than that in JY47. In addition, the regional yield (seed spacing: 5 cm) of jym165 increased by 2.42% compared with that of JY47 under high planting density. Comparative transcriptome analysis showed that the yellow-green leaf phenotype was closely related to photosynthesis and starch and sugar metabolism pathways. Genetic analysis suggests that the yellow-green leaf phenotype is controlled by a single recessive nuclear gene. Using Mutmap sequencing, the candidate regions related of leaf colour was narrowed to 3.44 Mb on Chr 10. Conclusions Abnormal chloroplast development in yellow-green mutants leads to a decrease in the photosynthetic pigment content and net photosynthetic rate, which affects the soybean photosynthesis pathway and starch and sugar metabolism pathways. Moreover, it has the potentiality to increase soybean yield under dense planting conditions. This study provides a useful reference for studying the molecular mechanisms underlying photosynthesis in soybean.

Abstract To further raise the gas extraction efficiency of the tight sandstone, the liquid nitrogen (LN2) freezing-thawing cycles method can be employed to improve the permeability of the low-permeability reservoirs. Permeability is generally regarded as a macroscopic description of the pore structure and usually has functional relationship to pore structure properties. The permeability of the rock is closely related to the change of microscopic pore structure. The permeability of rock depends on how the subzero temperatures changed the microscopic pore structure of rock, but it has not yet been confirmed obviously. In this study, the nuclear magnetic resonance (NMR) technique was adopted to investigate the pore structure evolution law and permeability of the tight sandstone with different LN2 freezing-thawing cycles. The results demonstrate that the LN2 freezing-thawing cycles promotes pore development and micro-fracture connection, and enhances the pore connectivity. The proportion of meso-pores, macro-pores and micro-fractures in the sandstone samples increases significantly, which provides a channel for the sandstone gas flow and extraction. Total porosity and effective porosity of the samples present a trend of rapid increase as the number of LN2 freezing-thawing cycles increasing, while the residual porosity decreases as the number of LN2 freezing-thawing cycles increasing. Coates model, SDR model (mean T2 model) and PP model were used to calculate and evaluate the permeability of the samples subjected to different LN2 freezing-thawing cycles. Furthermore, PP model can provide a better permeability estimate than the classical Coates and SDR model.

Based on the conventional observation， the cloud top blackbody brightness temperature data of Fengyun satellite， and the European Centre for Medium-Range Weather Forecasts 0.25°×0.25° ERA5 reanalysis data from 2006 to 2021， we have conducted a statistical analysis on the heavy precipitation events caused by extratropical cyclones over northern and northeastern China during the cold season.The results show that： （1） Most of the extratropical cyclones occluded during the explosive development phase， but the development process is different， with the Shapiro-Keyser （SK-type） and the classical Norwegian （NW-type） cyclones each accounting for half.The SK-type cyclone has a deep trough at 500 hPa， strong baroclinicity， and steering airflow in the north-northeast-orientation， resulting in westerly cyclone path， and northward， widespread precipitation； the NW-type cyclone has a shallow trough at 500 hPa， with weak cold advection behind the trough， and the steering airflow in the east-northeast orientation， resulting in an easterly cyclone path， more to the south and more intense precipitation.（2） The atmospheric rivers of the NW-type cyclone are more intensethan those of the SK-type cyclone， and the corresponding heavy precipitation is extensive and more intense.With the development of the cyclones， the atmospheric rivers of the SK-type cyclone gradually turn to a north-south orientation， and there is a clear backward-turning feature on the north side of the atmospheric river， resulting in a warm front precipitation center of the SK-type cyclone located in the northwest quadrant of the cyclone， and the warm front precipitation center of the NW-type cyclone is close to the center of the cyclones.（3） The warm front frontogenesis in the northwest quadrant of the SK-type cyclone is significantly more intense than that of the NW-type cyclone， and the intense lifting forced by the front is conducive to heavy snowfall.（4） The SK-type cyclone has an intense potential vorticity structure in the shape of treble-clef at 300 hPa， while the NW-type cyclone has weaker potential vorticity in the upper levels.The stratospheric potential vorticity over the SK-type cyclone extends downwards， connecting with the low-level potential vorticity to form a potential vorticity tower， with a deep warm occluded structure nearby； while， the upper-level potential vorticity of the NW-type cyclone does not extend downward significantly， and there is no potential vorticity tower generated.The SK-type cyclone first develops in the middle troposphere， and then reachesthe surface， while the NW-type cyclone develops from the lower troposphere.

Based on nine C-band Doppler radar observations of Heilongjiang Province and conventional data from 2010 to 2021， combined with 1-h interval ERA5 reanalysis data of 0.25°×0.25° from the European Center for Medium-Range Weather Forecasts， the types and activity characteristics of mesoscale precipitation bands associated with extratropical cyclones in Heilongjiang Province are statistically analyzed， and the similarities and differences in the environment fields of two types of mesoscale precipitation bands are compared through typical cases.The main results are： （1） Mesoscale precipitation bands are primarily divided into single， multi， transitory， and nonbanded.Precipitation bands are mainly located in southern and northeastern Heilongjiang and the northwest and northeast quadrants of surface cyclones， within 900 km from the cyclone centers， and occur in the mature stage of cyclones.The main movement types of mesoscale precipitation bands are laterally translating and hybrid.（2） Vertical profiles of physical quantities can well reflect differences in precipitation intensity of different precipitation bands.Single-banded bands have the most excellent low-level specific humidity and frontogenesis， causing the heaviest precipitation.Non-banded bands have extensively weaker low-level frontogenesis than single-banded bands， with maximum specific humidity near 800 hPa， causing a wide range of precipitation and a weaker precipitation intensity than single-banded bands.（3） The analysis of cases shows that both single-banded and multi-banded bands are located on the north side of the intense 850-hPa warm advection， the northeast quadrant of the surface cyclone， in a small moist symmetric stable or moist symmetric unstable environment.The direction of the mesoscale precipitation band is parallel to the frontogenesis.The differences between them are as follows： for the single-banded band， deformation leads to strong frontogenesis and the upward movement concentrated on a small area， accompanying the development and movement of the low-level low and the surface cyclone， while for the multi-banded， weak deformation and shallow frontogenesis accompanying little movement and intensity change， intense upper-level divergence and low-level warm advection caused more extensive upward motion with multiple upward centers， corresponding to multi bands.

Biomaterials play an integral role in treatment of external auditory canal (EAC) diseases. Regarding the special anatomic structure and physiological characteristics of EAC, careful selection of applicable biomaterials was essential step towards effective management of EAC conditions. The bioactive materials can provide reasonable biocompatibility, reduce risk of host pro-inflammatory response and immune rejection, and promote the healing process. In therapeutic procedure, biomaterials were employed for covering or packing the wound, protection of the damaged tissue, and maintaining of normal structures and functions of the EAC. Therefore, understanding and application of biomaterials was key to obtaining great rehabilitation in therapy of EAC diseases. In clinical practice, biomaterials were recognized as an important part in the treatment of different EAC diseases. The choice of biomaterials was distinct according to the requirements of various diseases. As a result, awareness of property regarding different biomaterials was fundamental for appropriate selection of therapeutic substances in different EAC diseases. In this review, we firstly introduced the characteristics of EAC structures and physiology, and EAC pathologies were summarized secondarily. From the viewpoint of biomaterials, the different materials applied to individual diseases were outlined in categories. Besides, the underlying future of therapeutic EAC biomaterials was discussed.

Abstract This study examined Education for Sustainable Development (ESD) in China spanning over two decades(1998–2023). Assisted with text mining tool of Itginsight, by combining latent Dirichlet allocation (LDA) modeling with social network analysis(SNA) and sentiment analysis, this study constructed a visualized analysis of the research status of ESD and explores the topics distribution and sentiment trends of Chinese scholars regarding ESD. The analysis shows that studies concerning ESD are displaying a “trending-declining” tendency with ample space for greater expansion. Existing researches have predominantly exhibited a predilection towards objectives, ideologies, methodologies, and themes concerning ESD. After further modeling, mapping multicluster topics, and conducting sentiment analysis on highly cited literature, it is found the focus of this discipline lies more on environmental education from different aspects, and an overriding sense of positivity concerning the inherent potential of ESD to drive transformative societal change is found. Despite the intricacies of various research themes, the scholarly consensus is that ESD represents a vital and indispensable means of addressing the pressing environmental and social challenges of our epoch, which should be optimized both theoretically and practically.

Abstract Background Caloric value is an important indicator of grassland ecosystem function, but the response of caloric value to nitrogen (N) addition and mowing is still unclear. We explored the adaptive changes of plant caloric value and energy standing crop along a N addition gradient after six-year NH4NO3 addition and mowing treatments in an Inner Mongolian temperate meadow steppe in northern China. Results We found that the response of plant caloric value to N addition at different organizational levels was diverse. The caloric value of legumes increased linearly with N addition rates. The caloric value of grasses exhibited a non-linear response trend, initially increasing followed by saturation or decrease, with a N response threshold present. Due to the dominance of grass species, the caloric value at the community level followed a similar pattern to that of the grasses along the N addition gradient. Under mowing, the caloric value of plants at each organizational level increased and usually mowing enhanced the N response threshold. Amongst these, the N response threshold of Leymus chinensis increased from 3.302 to 5.443 g N m−2 yr−1, grasses increased from 4.414 to 5.746 g N m−2 yr−1, and community increased from 5.373 to 9.216 g N m−2 yr−1. Under non-mowing treatment, the N response thresholds of the most dominant species, Leymus chinensis, and community energy standing crop were 10.001 and 15.119 g N m−2 yr−1, respectively. Under mowing, the energy standing crops showed a linear increasing trend. Conclusions N response thresholds of plant caloric value and energy standing crop vary at different organizational levels (community > functional group > species). The results reveal varying regulatory capabilities of plants on the ecological environment at different organizational levels. These findings enhance our understanding of plant-environment interactions in grassland ecosystems under N deposition from an energy perspective, which is of great significance to clarify the response mechanism of grassland ecosystem structure and function to N deposition.

Abstract Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a life-threatening autoimmune disease that often results in kidney failure caused by crescentic glomerulonephritis (GN). To date, treatment of most patients with ANCA-GN relies on non-specific immunosuppressive agents, which may have serious adverse effects and be only partially effective. Here, using spatial and single-cell transcriptome analysis, we characterize inflammatory niches in kidney samples from 34 patients with ANCA-GN and identify proinflammatory, cytokine-producing CD4+ and CD8+ T cells as a pathogenic signature. We then utilize these transcriptomic profiles for digital pharmacology and identify ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, as the strongest therapeutic drug to use. Moreover, four patients with relapsing ANCA-GN are treated with ustekinumab in combination with low-dose cyclophosphamide and steroids, with ustekinumab given subcutaneously (90 mg) at weeks 0, 4, 12, and 24. Patients are followed up for 26 weeks to find this treatment well-tolerated and inducing clinical responses, including improved kidney function and Birmingham Vasculitis Activity Score, in all ANCA-GN patients. Our findings thus suggest that targeting of pathogenic T cells in ANCA-GN patients with ustekinumab might represent a potential approach and warrants further investigation in clinical trials.

Abstract Colorectal cancer (CRC) ranks among the leading causes of cancer-related mortality worldwide, posing a significant public health challenge. Despite advancements in treatment strategies, prognosis for advanced CRC remains poor. Here, we investigate the role of CLK3 and its interaction with the c-Myc signaling pathway in CRC progression. Our study reveals significant overexpression of CLK3 in CRC tumor tissues, correlating with disease advancement, and demonstrates that CLK3 promotes CRC cell proliferation, mediated by its activation of MYC signaling through upregulation of c-MYC expression. In vivo experiments confirm the oncogenic role of CLK3, with its loss resulting in decreased tumor growth and c-MYC expression. These findings highlight CLK3 as a potential therapeutic target in CRC, offering insights into novel treatment strategies.

Abstract Respiratory pathogens infecting the human respiratory system are characterized by their diversity, high infectivity, rapid transmission, and acute onset. Traditional detection methods are time-consuming, have low sensitivity, and lack specificity, failing to meet the needs of rapid clinical diagnosis. Nucleic acid aptamers, as an emerging and innovative detection technology, offer novel solutions with high specificity, affinity, and broad target applicability, making them particularly promising for respiratory pathogen detection. This review highlights the progress in the research and application of nucleic acid aptamers for detecting respiratory pathogens, discussing their selection, application, potential in clinical diagnosis, and future development. Notably, these aptamers can significantly enhance the sensitivity and specificity of detection when combined with detection techniques such as fluorescence, colorimetry and electrochemistry. This review offers new insights into how aptamers can address the limitations of traditional diagnostic methods and advance clinical diagnostics. It also highlights key challenges and future research directions for the clinical application of nucleic acid aptamers.

Abstract We investigated the clinical characteristics of primary aldosteronism (PA) screened from patients with hypertension in China. The participants were hypertensive patients who were suspected of PA and registered in the China Primary Aldosteronism Prospective Study. Plasma aldosterone‐to‐renin ratio (ARR) was used as the screening test. In patients screened positive for PA, that is, an ARR exceeding the thresholds and plasma aldosterone concentration (PAC) > 100 pg/mL, a confirmatory test was performed for diagnosis. Patients with PA underwent a CT scan and adrenal venous sampling for subtyping. Of the 1497 screened patients, 754 (50.4%) had an ARR exceeding the diagnostic threshold and 637 (84.5% of those eligible) were registered. These registered hypertensive patients with suspected PA had a mean (standard deviation) age of 52.6 ± 12.1 years, and included 442 (58.6%) women. In multiple stepwise logistic regression, the significant odds ratios for the presence of diagnosed (n = 490) versus suspected and non‐diagnosed PA (n = 147) were 4.54 (95% CI: 2.78‐7.39) for a history of hypokalemia, 0.79 (95% CI: 0.64‐0.98) for a 0.9 mmol/l higher serum total cholesterol, and 2.25 (95% CI: 1.63‐3.10) for a doubling of PAC in the supine or standing/sitting position. In multiple stepwise logistic regression, the significant odds ratios for the presence of unilateral (n = 135) versus bilateral PA (n = 53) were 3.04 (95% CI: 1.90‐4.87) for a 0.4 mmol/l lower minimum serum potassium concentration and 1.86 (95% CI: 1.20‐2.86) for a 0.3 mmol/l higher serum high‐density lipoprotein cholesterol. PA might be a biochemical continuum in the adrenal hypersecretion of aldosterone as well as hypokalemia.

Abstract This study employs China's Yangtze River Economic Belt strategy as a quasi‐natural experiment to investigate the impact of prioritizing green development on economic growth. Our empirical findings show that the strategy significantly reduces urban industrial wastewater discharge. It helps transition the region's industries towards technology‐driven service sectors while maintaining a steady economic growth rate. On average, cities in the Yangtze River Economic Belt see a 21.9% decrease in annual industrial wastewater discharge, a 1.9% increase in economic growth rate, a 4.9% rise in the proportion of service industries' contribution to GDP, and a 2.4% increase in the number of employees in productive service industries. Moreover, our empirical results highlight the heterogeneity in the effects of the strategy across different regions, which can be attributed to factors such as population density, infrastructure, levels of human capital, and government governance. The implementation of the Yangtze River Economic Belt strategy offers valuable insights for developing countries on how to balance between economic development and environmental protection.

Blue light induced eye damage (BLED) belongs to modern diseases. It is an ophthalmic disease caused by prolonged exposure to electronic devices or screens containing a large amount of high-energy short waves (blue light). Specific symptoms include dryness and discomfort in the eyes, blurred vision, headache, insomnia, and in severe cases, it may also cause various eye diseases such as cataracts and glaucoma. At present, the development of health products and drugs for eye blue light injury faces many difficulties. Therefore, further exploration and research are needed on the pathogenesis, pathophysiology, and pharmacological mechanisms of blue light injury. Natural medicine ingredients and preparations have unique advantages in targeting eye blue light injury fatigue products due to their multi-component synergistic effects, overall regulation, and mild and safe characteristics. Starting from the disease-related mechanisms and pathophysiological characteristics of eye blue light injury, this article elucidates the pharmacological mechanisms of various drugs for treating eye blue light injury. At the same time, it reviews the research on in vitro cultured cell and animal model conditions for blue light injury eyes, in order to provide reference for subsequent blue light injury modeling experiments. And explore future research directions to provide new ideas and methods for the prevention and treatment of BLED.

Chlorophyll density (ChD) can reflect the photosynthetic capacity of the winter wheat population, therefore achieving real-time non-destructive monitoring of ChD in winter wheat is of great significance for evaluating the growth status of winter wheat. Derivative preprocessing has a wide range of applications in the hyperspectral monitoring of winter wheat chlorophyll. In order to research the role of fractional-order derivative (FOD) in the hyperspectral monitoring model of ChD, this study based on an irrigation experiment of winter wheat to obtain ChD and canopy hyperspectral reflectance. The original spectral reflectance curves were preprocessed using 3 FOD methods: Grünwald-Letnikov (GL), Riemann-Liouville (RL), and Caputo. Hyperspectral monitoring models for winter wheat ChD were constructed using 8 machine learning algorithms, including partial least squares regression, support vector regression, multi-layer perceptron regression, random forest regression, extra-trees regression (ETsR), decision tree regression, K-nearest neighbors regression, and gaussian process regression, based on the full spectrum band and the band selected by competitive adaptive reweighted sampling (CARS). The main results were as follows: For the 3 types of FOD, GL-FOD was suitable for analyzing the change process of the original spectral curve towards the integer-order derivative spectral curve. RL-FOD was suitable for constructing the hyperspectral monitoring model of winter wheat ChD. Caputo-FOD was not suitable for hyperspectral research due to its insensitivity to changes in order. The 3 FOD calculation methods could all improve the correlation between the original spectral curve and Log(ChD) to varying degrees, but only the GL method and RL method could observe the change process of correlation with order changes, and the shorter the wavelength, the smaller the order, and the higher the correlation. The bands screened by CARS were distributed throughout the entire spectral range, but there was a relatively concentrated distribution in the visible light region. Among all models, CARS was used to screen bands based on the 0.3-order RL-FOD spectrum, and the model constructed using ETsR reached the best accuracy and stability. Its R2c, RMSEc, R2v, RMSEv, and RPD were 1.0000, 0.0000, 0.8667, 0.1732, and 2.6660, respectively. In conclusion, based on the winter wheat ChD data set and the corresponding canopy hyperspectral data set, combined with 3 FOD calculation methods, 1 band screening method, and 8 modeling algorithms, this study constructed hyperspectral monitoring models for winter wheat ChD. The results showed that based on the 0.3-order RL-FOD, combined with the CARS screening band, ETsR modeling has the highest accuracy, and hyperspectral estimation of winter wheat ChD can be realized. The results of this study can provide some reference for the rapid and nondestructive estimation of ChD in winter wheat.

Narcolepsy is a sleep-wake disorder with an onset commonly seen in individuals aged 10–30 years. Due to various reasons, the diagnosis of narcolepsy often experiences a delay of at least ten years. Diagnosing narcolepsy in children is particularly challenging due to atypical symptoms, leading to frequent misdiagnosis or missed diagnoses. We report a case of narcolepsy in a four-year-old girl to provide insights into the early diagnosis and treatment of narcolepsy in children. As a chronic condition, narcolepsy can lead to decreased quality of life, including psychological issues such as depression and anxiety. Furthermore, there are few randomized controlled trials involving pediatric narcolepsy patients. To provide a comprehensive treatment approach for pediatric narcolepsy, we review the current progress in the treatment of narcolepsy in children.

The acceleration of urbanization and development of marine resources has led to the imbalance of land structure, which threatens the sustainable development of the human living environment. Exploring the spatial distribution patterns of land-sea and its spatio-temporal evolution characteristics is an important initiative to resolve conflicts and optimise the spatial structure of land-sea use. Taking the Liaoning Coastal Economic Belt as an example, this paper constructs a system to measure the value of Production-Living-Ecological Functions (PLEF) of the coastal zone and realizes the identification of Production-Living-Ecological Spaces (PLES) and the division of their combination patterns. At the same time, it analyses the spatio-temporal evolution of PLES using land use transfer matrix, center of gravity transfer and standard deviation ellipse models and explores the interaction mechanism of PLES from the perspective of land-sea coordination. The results show that: (1) The production and living spaces on land are concentrated near the coastline, and the ecological space is mainly distributed in the mountainous forest area. The sea is dominated by the production space, and the living and ecological spaces occupy a relatively small proportion. (2) While the land has significant multifunctionality, the sea has a single PLEF, with the production function dominating and accounting for more than 90%. (3) In the period 2005–2010, the frequency of mutual transformation of the different PLES was the highest. The increase is mainly in the living space on land and the production space at sea. (4) From 2005 to 2010, the patterns of land and sea PLES changed significantly, and from 2010 to 2020, they were relatively stable. This study analyses the spatial structure of land-sea from the perspective of spatial multifunctionality and proposes optimization schemes based on land-sea interactions, which can provide decision support for the identification and optimization of coastal zone space and sustainable development.

Abstract Background Activin A, a noteworthy member of the TGF‐β superfamily. Activin A can regulate the biological functions of various immune cells, such as macrophages, neutrophils, NK cells, etc. The purpose of this study is to investigate the regulatory effect and related mechanisms of activin A on CD8+ T cells. Methods This study established a mouse subcutaneous transplantation model of hepatoma to explore whether activin A has a regulatory effect of CD8+ T cells. And reveal the biological characteristics of ActRIIA high CD8+ T cells. Results We discovered that CD8+ T cells express ActRIIA, ActRIIB, and Smad2,3,4. Unlike high‐dose activin A, low‐dose activin A increased the content of CD8+ T cells while also suppressing tumor growth. In addition, low‐dose activin A promoted expression of perforin, granzyme B, CD69, CD11c, CD49b, Ki67 and ActRIIA in CD8+ T cells. And the results indicated that high‐dose activin A promotes the expression of PPM1A in T cells, while low‐dose activin A has no effect on these cells. The tumor contained more ActRIIA high CD8+ T cells compared to the peripheral blood and spleen. ActRIIA high CD8+ T cells highly express cytotoxic molecules and cytokines. And ActRIIA high CD8+ T cells not only expressed high levels of activation/co‐stimulatory markers CD69, CD278, and CD28, but also high levels of inhibitory markers CD366 and KLRG1. Different chemokine receptors displayed varying levels of expression in ActRIIA high CD8+ T cells. Additionally, these cells have a high proliferative potential. Finally, overexpression of Mettl3 inhibited the expression of ActRIIA in CD8+ T cells. Conclusions This study demonstrated that low‐dose activin A enhanced the anti‐tumor effect of CD8+ T cells, and ActRIIA high CD8+ T cells actively contribute to tumor immunity.

IntroductionCoastal wetlands play an important role in the global ecosystem, yet they are increasingly facing ecological degradation due to pollution and the spread of invasive Spartina alterniflora (S. alterniflora). Among the environmental challenges, microplastics (MPs) contamination in S. alterniflora-invaded coastal wetlands is of growing concern. However, the effects of MPs pollution in S. alterniflora-invaded coastal wetlands are not clear.MethodsThis study investigated the effects of S. altemiflora invasion on the distribution of MPs and the effects of MPs pollution on the physicochemical properties of sediments and the structure of microbial communities in the Tiaozini wetland of Jiangsu Province, China.Results and discussionThe total MPs abundance of the S. altemiflora single-plant area was the highest (16.338 x103 items/kg d.w.). Polyurethane and Chlorinated polyisoprene are typical MPs types in the study area. Polyurethane exhibits high abundance at all sampling sites, while Chlorinated polyisoprene is one of the dominant MPs types in the single-plant and sub-mature area of S. alterniflora. The results showed that the invasion of S. alterniflora promoted the accumulation of MPs in the sediments of the coastal wetland. This accumulation increased the total organic carbon (TOC), available phosphorus (AP) and total nitrogen (TN) contents. Moreover, MPs pollution increased the ALP and SUC enzyme activities of sediment. In addition, MPs contamination increased the abundance of Proteobacteria and Bacteroidota in the sediments. This study highlights the complex interactions between MPs pollution and S. alterniflora invasion, providing the foundation for understanding the synergistic impacts of these stressors on coastal wetland ecosystems.

BackgroundHJIG is a potential treatment for erectile dysfunction (ED) that has been used in China for over 20 years. We conducted a multi-center, double-blind, randomized, placebo-controlled trial to evaluate the effectiveness and safety of the Chinese Herbal Medicine, Hongjing I granule (HJIG), in patients with mild to moderate erectile dysfunction (ED).MethodsThis study is structured as a randomized, double-blind, placebo-controlled trial, executed across multiple centers. The recruitment strategy is primarily oriented towards patients demonstrating a pronounced preference for solely leveraging traditional Chinese medicine (TCM) interventions, a preference that is widely observed within TCM healthcare settings. A total of 100 patients, presenting with mild to moderate ED, specifically linked to the traditional diagnostic criteria of qi deficiency and blood stasis, will be enrolled. These participants will be randomly distributed between the HJIG (N = 50) and placebo (N = 50) arms. The designated treatment period is set at 8 weeks. Primary outcome measures encompass the International Index of Erectile Function-Erectile Function domain (IIEF-EF) score, the Sexual Encounter Profile (SEP), and scores derived from the traditional Chinese medicine symptom evaluation.ResultsOf the 122 men enrolled, the baseline IIEF-EF score averaged 16.00 [IQR: 13.00, 18.00]. Eight weeks post-randomization, the HJIG group demonstrated a mean change in IIEF-EF scores of 7.80 (±3.25), compared to 3.33 (±3.90) in the placebo group, signifying a marked difference (P < 0.001). The median alterations in SEP3 scores were 0.50 [IQR: 0.36, 0.75] for the HJIG group and 0.50 [0.20, 0.67] for the placebo group, revealing a statistically relevant distinction (P = 0.05). In both primary outcomes, HJIG proved superior to the placebo. Additionally, improvements in TCM symptom scores were notably greater in the HJIG group relative to the placebo, with no adverse events reported across both groups.ConclusionThe Hongjing I granule significantly improved symptoms in patients with mild to moderate ED. However, to validate these findings, further extended randomized trials are warranted.Clinical Trial RegistrationThe study has been registered in the Chinese Clinical Trial Registry (ChiCTR) and the registration number was ChiCTR2000041127.

Abstract Parrot feather (Myriophyllum aquaticum) is an introduced, noninvasive amphibious plant found in coastal provinces, but it has the potential to become an invasive species in China. The plant is heterophyllous, with both emergent (aerial) and submerged (aquatic) leaves, and has two distinct root types: aquatic (adventitious) and edaphic (sediment) root systems. This morphological plasticity allows M. aquaticum to effectively absorb nutrients from different layers of the environment, making it a suitable model plant for exploring nutrient dynamics in both water and soil systems and investigating how wetland plants respond to cultural eutrophication. We designed an outdoor mesocosm experiment to assess plant growth traits and root topological indices in response to different nitrogen (N) and phosphorus (P) concentrations. The results indicated that the plant has a high tolerance to N loading. In contrast, the P content had greater impacts than the N content on plant growth and root topological indices, indicating that the P content was the main influencing factor affecting and suppressing the development of M. aquaticum. The aquatic or edaphic root branching did not change, but the aquatic root topology of M. aquaticum exhibited similar stable trends with increasing P concentration, indicating typical herringbone branching; additionally, its edaphic roots exhibited decreasing topological indices, indicating more typical dichotomous branching with increasing P concentration. The plant has a high tolerance to N, and it may become invasive following the current trend of increasing cultural eutrophication.

Nitrogen-doping carbon dots have attracted broad interest in recent years due to their excellent spectral properties and promising applications. However, the luminescence mechanism of these carbon dots still lacks support from time-resolved spectroscopy. In this work, carbon dots were synthesized using p-phenylenediamine as a precursor (p-CDs), and their excited state dynamics were studied using transient absorption and time-resolved fluorescence spectroscopy. Experimental results reveal the origins of dual fluorescence and the synergistic effect mechanism involving the core state, the surface state, and solvent relaxation. Fluorescence lifetime imaging of p-CDs was performed in cells, highlighting their great potential for applications in biological fields.

BackgroundTransient Receptor Potential Melastatin 4 (TRPM4), a non-selective cation channel, plays a critical role in cardiac conduction abnormalities. Brg1, an ATP-dependent chromatin remodeler, is essential for regulating gene expression in both heart development and disease. Our previous studies demonstrated Brg1 impacted on cardiac sodium/potassium channels and electrophysiological stability, its influence on TRPM4 expression and function remained unexplored.MethodsWe investigated the role of Brg1 in regulating TRPM4 expression and function through overexpression and knockdown experiments in mouse cardiomyocytes and TRPM4-overexpressing HEK293 cells by western blot, qPCR, immunofluorescence staining and patch clamp techniques. Cardiomyocytes were exposed to hypoxia for 12 h to mimic cardiac stress, and Brg1 inhibition was performed to assess its impact on TRPM4 under hypoxia. Bioinformatic analyses (STRING and JASPAR databases), Co-immunoprecipitation (Co-IP), dual luciferase reporter assays, and Chromatin Immunoprecipitation (ChIP) were employed to study the interaction between Brg1, RUNX1, and TRPM4 transcription regulation.ResultsBrg1 positively regulated TRPM4 expression in mouse cardiomyocytes and modulated TRPM4 current in TRPM4-overexpressing HEK293 cells. Brg1 inhibition markedly diminishes TRPM4’s hyperexpression in cardiomyocytes exposed to hypoxia. Integrative analyses utilizing STRNG databases and Protein Data Bank unveiled a putative interaction between Brg1 and the transcription factor RUNX1, and we substantiated the interaction between Brg1 and RUNX1. Several binding sites of RUNX1 with the TRPM4 promoter region were predicted by the JASPAR database, and empirical validation substantiated Brg1 modulated TRPM4 promoter activity via RUNX1 engagement. ChIP confirmed that Brg1 interacted with RUNX1 forming a transcriptional complex that located in TRPM4 promoter.ConclusionOur study demonstrated that Brg1 and RUNX1 formed a transcriptional complex that modulated TRPM4 expression and function, especially under hypoxic conditions. These findings provided new insights into TRPM4 regulation and highlighted its potential as a therapeutic target for cardiac hypoxia-related disorders.

This study aims to investigate the influence of corn cob particles on pore structure of mortar. By using NMR technology, the pore parameters of fast-hardening sulfoaluminate cement mortar (SAC) and ordinary Portland cement mortar (PO) were measured and compared. The influence of corncob particles on the mechanical properties of eco-mortar was evaluated by uniaxial compression test. The results indicate that medium and large pores of both SAC and PO increases with corn cob particle, as well as the porosity. The fractal dimensions of harmful and multiple harmful pores are negatively correlated with the volume fraction of corn cob particles. The addition of corn cob particles reduced the overall fractal dimension of the mortar and decreased the complexity of internal pores. The probability density function of grayscale values transitions from being “thin and tall” to “short and wide”, with an increasing proportion of high grayscale values. This leads to an increase in the proportion of large pores within the mortar, resulting in a continuous deterioration of pore structure. The addition of corn cob particles greatly reduces the strength of SAC and PO, but the peak stress of SAC is higher than that of PO. When corn cob particle content is 30 wt% and 50 wt%, the peak stress of SAC is increased by 23.37% and 14.25%, respectively, compared with the peak stress of PO.

This study proposes AVARA, an innovative adaptive Voronoi diagram algorithm explicitly designed for residential areas containing adjacent polygons. AVARA addresses the complex task of balancing computational efficiency and boundary position accuracy in existing Voronoi algorithms based on occurrence element discretization and difficulties constructing Voronoi diagrams for topologically adjacent polygonal objects. AVARA leverages interpolation strategies established on the classification result of neighbor pairs using co-edge relationships of residential area centroids. Additionally, AVARA incorporates graphical Boolean operations and node merging. The experiments used residential area datasets at 1:50,000, 1:10,000, and 1:2,000 map scales. The results showed that AVARA outperformed the Voronoi diagram algorithms based on intervisible points (VBIVP) and the equal-interval dense point method (VBEDP). AVARA achieved the highest accuracy rate in constructing Voronoi diagrams, with a 50% improvement. It also exhibited superior local position accuracy, demonstrating significant time performance improvements of 349.12% and 90.7% using datasets at map scales of 1:50,000 and 1:10,000, respectively. In the experiment using a dataset at a map scale of 1:2,000, AVARA consumed slightly less time than VBEDP with a 0.6 m interval. These findings highlight the significant overall advantage of AVARA. Additionally, the effectiveness of the algorithm was further validated using a large-scale building dataset.

Background Cellular senescence, macrophages infiltration, and vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation participate in the pathophysiology of vascular calcification in chronic kidney disease (CKD). Senescent macrophages are involved in the regulation of inflammation in pathological diseases. In addition, senescent cells spread senescence to neighboring cells via Interferon-induced transmembrane protein3 (IFITM3). However, the role of senescent macrophages and IFITM3 in VSMCs calcification remains unexplored.Aims To explore the hypothesis that senescent macrophages contribute to the calcification and senescence of VSMCs via IFITM3.Methods Here, the macrophage senescence model was established using Lipopolysaccharides (LPS). The VSMCs were subjected to supernatants from macrophages (MCFS) or LPS-induced macrophages (LPS-MCFS) in the presence or absence of calcifying media (CM). Senescence-associated β-galactosidase (SA-β-gal), Alizarin red (AR), immunofluorescent staining, and western blot were used to identify cell senescence and calcification.Results The expression of IFITM3 was significantly increased in LPS-induced macrophages and the supernatants. The VSMCs transdifferentiated into osteogenic phenotype, expressing higher osteogenic differentiation markers (RUNX2) and lower VSMCs constructive makers (SM22α) when cultured with senescent macrophages supernatants. Also, senescence markers (p16 and p21) in VSMCs were significantly increased by senescent macrophages supernatants treated. However, IFITM3 knockdown inhibited this process.Conclusions Our study showed that LPS-induced senescence of macrophages accelerated the calcification of VSMCs via IFITM3. These data provide a new perspective linking VC and aging, which may provide clues for diagnosing and treating accelerated vascular aging in patients with CKD.

Mycoviruses can alter the biological characteristics of host fungi, including change virulence or pathogenicity of phytopathogens and entomopathogenic fungi (EPF). However, most studies on the mycoviruses found in EPF have focused on the effects of the viruses on the virulence of host fungi towards insect pests, with relatively few reports on the effects to the host fungi with regard to plant disease resistance in hosts. The present study investigated the effects of the mycovirus Beauveria bassiana chrysovirus 2 (BbCV2) virus infection on host biological characteristics, evaluated antagonistic activity of BbCV2 against two phytopathogenic fungi (Sclerotinia sclerotiorum and Botrytis cinerea), and transcriptome analysis was used to reveal the interactions between viruses and hosts. Our results showed that BbCV2 virus infection increased B. bassiana‘s growth rate, spore production, and biomass, it also enhanced the capacity of host fungi and their metabolic products to inhibit phytopathogenic fungi. BbCV2 virus infection reduced the contents of the two pathogens in tomato plants significantly, and transcriptome analysis revealed that the genes related to competition for ecological niches and nutrition, mycoparasitism and secondary metabolites in B. bassiana were significantly up-regulated after viral infection. These findings indicated that the mycovirus infection is an important factor to enhance the ability of B. bassiana against plant disease after endophytic colonization. We suggest that mycovirus infection causes a positive effect on B. bassiana against phytopathogens, which should be considered as a potential strategy to promote the plant disease resistance of EPF.