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Chalkiness is one of the most important agronomic traits in rice breeding, which directly affects the quality of rice seed. In this study, we identified a chalkiness endosperm mutant, chalk-h, from N-methyl-N-nitrosourea (MNU)-induced japonica rice cultivar Hwacheong (HC). Compared with wild type (WT)-HC, chalk-h showed severe chalkiness in the endosperm, yellowish green leaves, as well as reduced plant height. Scanning electron microscopy (SEM) analysis showed that starch grains in the chalk-h mutant were irregular in size and loosely arranged, with large gaps between granules, forming ovoid or orbicular shapes. MutMap analysis revealed that the phenotype of chalk-h is controlled by a single recessive gene LOC_Os11g39670 encoding seryl-tRNA synthetase, which is renamed as CHALK-H. A point mutation occurs in chalk-h on the sixth exon (at nucleotide 791) of CHALK-H, in which adenine (A) is replaced by thymidine (T), resulting in an amino acid codon change from glutamine (Glu) to valine (Val). The chalk-h mutant exhibited a heat-sensitive phenotype from the 3-leaf stage, including yellow-green leaves and reduced pigment content. The transcriptional expression of starch synthesis-related genes was down-regulated in the chalk-h mutants compared to WT-HC at different grain-filling stages. With an increase in temperature, the expression of photosynthesis-related genes was down-regulated in the chalk-h mutant compared to WT-HC. Overexpression of CHALK-H rescued the phenotype of chalk-h, with endosperm and leaf color similar to those of WT-HC. Our findings reveal that CHALK-H is a causative gene controlling chalkiness and leaf color of the chalk-h mutant. CHALK-H is the same gene locus as TSCD11, which was reported to be involved in chloroplast development under high temperature. We suggest that CHALK-H/TSCD11 plays important roles not only in chloroplast development, but also in photosynthesis and starch synthesis during rice growth and development, so it has great application potential in rice breeding for high quality and yield.

Abstract In recent years, to improve air quality, significant efforts have been made to reduce regional aerosols including China, Europe and North America, which have potential impacts on climate. In this study, fast and slow climate responses in China to changes in domestic and foreign anthropogenic emissions of aerosols and precursors from 2013 to 2019 are investigated using the Community Earth System Model version 1 (CESM1). Aerosol emissions changes, especially reductions in China, North America and Europe, during 2013–2019 resulted in surface air temperature increases across the Northern Hemisphere. Global aerosol changes induce a regional warming of 0.2 °C in China, equally contributed by domestic and foreign emissions changes. China’s domestic emission reductions lead to a regional average temperature rise of 0.1°C, primarily driven by rapid atmospheric adjustments over eastern China. Foreign aerosol changes, particularly reductions in North America and Europe, also contributed to a 0.1°C warming in China through slow oceanic processes. This warming in China induced by foreign aerosol changes is due to a teleconnection between the aerosol-induced anomalous regional warming in Eastern U.S.-North Atlantic Ocean-Europe and the downstream East Asian climate through anomalous wave trains propagation. The comparable influence of domestic and foreign aerosol changes on climate in China underscores the importance of international collaboration in climate mitigation endeavors.

Nitroreductase (NTR) is an enzyme expressed at an abnormally high level in solid tumors, which is associated with the hypoxia level in tumors. The establishment of a high-performance and convenient fluorescent platform for the fast monitoring of NTR is of pivotal importance. Herein, a novel host–guest complex was created by encapsulating a fluorescent substrate GP-NTR within a metal–organic capsule Zn-MPB that included a NADH mimic for the detection of hypoxia via responding to nitroreductase (NTR) with fast responsiveness and good fluorescence imaging. Notably, the double-substrate process was streamlined to a single–substrate process by the host–guest supramolecular method in the catalytic process of NTR, which enabled the reaction to be independent of the cofactor NADH supply and shortened the distance between the substrate and the active site of NTR. The increasing fluorescence intensity of Zn-MPB⊃GP-NTR exhibits a linear relationship with NTR concentration and shows a fast response toward NTR in solution in tens of seconds. Zn-MPB⊃GP-NTR also displays high sensitivity to NTR with a low detection limit of 6.4 ng/mL. Cells and in vivo studies have confirmed that Zn-MPB⊃GP-NTR could be successfully applied for the fast imaging of NTR in NTR-overexpressed tumor cells and tumor-bearing animals. The host–guest platform not only provides a new avenue for the design and optimization of a fluorescence detection platform for the rapid and quantitative detection of NTR activity, but also offers an imaging tool for the early diagnosis of hypoxia-related tumors.

By constructing a complex network model grounded in time series analysis, this study delves into the intricate relationships between the stock markets of 18 countries worldwide. Utilizing 31 distinct time series distance functions to formulate the network, we employ Hamming distance to quantify the resemblance between networks derived from different distance functions. By modulating the network density through distance percentiles (p=0.1, 0.3, 0.5), we demonstrate the similarity of various distance functions across multiple density levels. Our findings reveal that certain distance functions exhibit high degrees of similarity across varying network densities, suggesting their potential for mutual substitution in network construction. Furthermore, the centroid network identified via hierarchical cluster analysis highlights the similarities between the stock markets of different nations, mirroring the intricate interconnections within the global financial landscape. The insights gained from this study offer crucial perspectives for comprehending the intricate network structure of global financial time series data, paving the way for further analysis and prediction of global financial market dynamics.

Abstract Background High-copper diets have been widely used to promote growth performance of pigs, but excess copper supplementation can also produce negative effects on ecosystem stability and organism health. High-copper supplementation can damage the intestinal barrier and disturb the gut microbiome community. However, the specific relationship between high-copper-induced intestinal damage and gut microbiota or its metabolites is unclear. Objective Using fecal microbiota transplantation and metagenomic sequencing, responses of colonic microbiota to a high-copper diet was profiled. In addition, via comparison of specific bacteria and its metabolites rescue, we investigated a network of bacteria-metabolite interactions involving conversion of specific metabolites as a key mechanism linked to copper-induced damage of the colon. Results High copper induced colonic damage, Lactobacillus extinction, and reduction of SCFA (acetate and butyrate) concentrations in pigs. LefSe analysis and q-PCR results confirmed the extinction of L. johnsonii. In addition, transplanting copper-rich fecal microbiota to ABX mice reproduced the gut characteristics of the pig donors. Then, L. johnsonii rescue could restore decreased SCFAs (mainly acetate and butyrate) and colonic barrier damage including thinner mucus layer, reduced colon length, and tight junction protein dysfunction. Given that acetate and butyrate concentrations exhibited a positive correlation with L. johnsonii abundance, we investigated how L. johnsonii exerted its effects by supplementing acetate and butyrate. L. johnsonii and butyrate administration but not acetate could correct the damaged colonic barrier. Acetate administration had no effects on butyrate concentration, indicating blocked conversion from acetate to butyrate. Furthermore, L. johnsonii rescue enriched a series of genera with butyrate-producing ability, mainly Lachnospiraceae NK4A136 group. Conclusions For the first time, we reveal the microbiota-mediated mechanism of high-copper-induced colonic damage in piglets. A high-copper diet can induce extinction of L. johnsonii which leads to colonic barrier damage and loss of SCFA production. Re-establishment of L. johnsonii normalizes the SCFA-producing pathway and restores colonic barrier function. Mechanistically, Lachnospiraceae NK4A136 group mediated conversion of acetate produced by L. johnsonii to butyrate is indispensable in the protection of colonic barrier function. Collectively, these findings provide a feasible mitigation strategy for gut damage caused by high-copper diets. Video Abstract

Abstract Preventing tau aggregation is a potential therapeutic strategy in Alzheimer’s disease and other tauopathies. Recently, liquid–liquid phase separation has been found to facilitate the formation of pathogenic tau conformations and fibrillar aggregates, although many aspects of the conformational transitions of tau during the phase transition process remain unknown. Here, we demonstrate that the tau aggregation inhibitor methylene blue promotes tau liquid–liquid phase separation and accelerates the liquid-to-gel transition of tau droplets independent of the redox activity of methylene blue. We further show that methylene blue inhibits the conversion of tau droplets into fibrils and reduces the cytotoxicity of tau aggregates. Although gelation slows down the mobility of tau and tubulin, it does not impair microtubule assembly within tau droplets. These findings suggest that methylene blue inhibits tau amyloid fibrillization and accelerates tau droplet gelation via distinct mechanisms, thus providing insights into the activity of tau aggregation inhibitors in the context of phase transition.

Abstract Nonsteroidal anti-inflammatory drugs compose one of the most widely used classes of medications, but the risks for early development remain controversial, especially in the nervous system. Here, we utilized zebrafish larvae to assess the potentially toxic effects of nonsteroidal anti-inflammatory drugs and found that sulindac can selectively induce apoptosis of GABAergic neurons in the brains of zebrafish larvae brains. Zebrafish larvae exhibit hyperactive behaviour after sulindac exposure. We also found that akt1 is selectively expressed in GABAergic neurons and that SC97 (an Akt1 activator) and exogenous akt1 mRNA can reverse the apoptosis caused by sulindac. Further studies showed that sulindac binds to retinoid X receptor alpha (RXRα) and induces autophagy in GABAergic neurons, leading to activation of the mitochondrial apoptotic pathway. Finally, we verified that sulindac can lead to hyperactivity and selectively induce GABAergic neuron apoptosis in mice. These findings suggest that excessive use of sulindac may lead to early neurodevelopmental toxicity and increase the risk of hyperactivity, which could be associated with damage to GABAergic neurons.

Abstract Background Thoracic aortic aneurysm or dissections (TAADs) represent a group of life-threatening diseases. Genetic aetiology can affect the age of onset, clinical phenotype, and timing of intervention. We conducted a prospective trial to determine the prevalence of pathogenic variants in TAAD patients and to elucidate the traits related to harbouring the pathogenic variants. One hundred and one unrelated TAAD patients underwent genetic sequencing and analysis for 23 TAAD-associated genes using a targeted PCR and next-generation sequencing-based panel. Results A total of 47 variants were identified in 52 TAAD patients (51.5%), including 5 pathogenic, 1 likely pathogenic and 41 variants of uncertain significance. The pathogenic or likely pathogenic (P/LP) variants in 4 disease-causing genes were carried by 1 patient with familial and 5 patients with sporadic TAAD (5.9%). In addition to harbouring one variant causing familial TAAD, the FBN1 gene harboured half of the P/LP variants causing sporadic TAAD. Individuals with an age of onset less than 50 years or normotension had a significantly increased genetic risk. Conclusions TAAD patients with a younger age at diagnosis or normotension were more likely to carry a P/LP variant; thus, routine genetic testing will be beneficial to a better prognosis through genetically personalized care prior to acute rupture or dissection.

Abstract Oxygen isotope anomaly of nitrate aerosol (∆17O-NO3 −) contributes to understanding the atmospheric nitrogen chemistry in the polar oceans. Here, ∆17O-NO3 − of the aerosol samples was analyzed based on a cruise from East Asia to the Arctic Ocean to explore the nitrate formation mechanisms. ∆17O-NO3 − decreased with the increase of latitude, especially when after entering the Arctic Circle. ∆17O-NO3 − (e.g., 11.5‰–21.2‰) was extremely low while crossing the sea ice-covered Arctic Ocean. This is most likely influenced by the combined enhancement of hydroxyl (OH) and peroxy (HO2 + RO2) radicals derived by sea ice under permanent sunlight period. In addition, the obvious increase in the ∆17O-NO3 − of return trip with shortened daytime indicated the advantage of nocturnal pathways (NO3 related) with the higher ∆17O endmembers. The mutation of ∆17O-NO3 − can reflect the change of NOx conversion pathways to nitrate, and it can be more sensitive to the change of radical chemistry related to atmospheric oxidation.

Nine major cell populations among 46,716 cells were identified in mouse intestinal ischemia‒reperfusion (II/R) injury by single-cell RNA sequencing. For enterocyte cells, 11 subclusters were found, in which enterocyte cluster 1 (EC1), enterocyte cluster 3 (EC3), and enterocyte cluster 8 (EC8) were newly discovered cells in ischemia 45 min/reperfusion 720 min (I 45 min/R 720 min) group. EC1 and EC3 played roles in digestion and absorption, and EC8 played a role in cell junctions. For TA cells, after ischemia 45 min/reperfusion 90 min (I 45 min/R 90 min), many TA cells at the stage of proliferation were identified. For Paneth cells, Paneth cluster 3 was observed in the resting state of normal jejunum. After I 45 min/R 90 min, three new subsets were found, in which Paneth cluster 1 had good antigen presentation activity. The main functions of goblet cells were to synthesize and secrete mucus, and a novel subcluster (goblet cluster 5) with highly proliferative ability was discovered in I 45 min/R 90 min group. As a major part of immune system, the changes in T cells with important roles were clarified. Notably, enterocyte cells secreted Guca2b to interact with Gucy2c receptor on the membranes of stem cells, TA cells, Paneth cells, and goblet cells to elicit intercellular communication. One marker known as glutathione S-transferase mu 3 (GSTM3) affected intestinal mucosal barrier function by adjusting mitogen-activated protein kinases (MAPK) signaling during II/R injury. The data on the heterogeneity of intestinal cells, cellular communication and the mechanism of GSTM3 provide a cellular basis for treating II/R injury.

Abstract Phytopathogens secrete numerous effectors that facilitate their infection and colonization processes. However, the pathogenic mechanism of effectors in Cytospora chrysosperma, the causal agent of canker disease in many woody plants, remains poorly understood. In this study, we identified five glycoside hydrolase family 12 (GH12) effector genes in C. chrysosperma genome, all of which were significantly upregulated during the infection stages. Among them, CcEG1, which contains an additional carbohydrate-binding module family 1 domain (CBM1) at the C-terminal, was selected for further analysis. Transient expression studies showed that CcEG1 was localized to the apoplastic region of Nicotiana benthamiana and acted as an elicitor to induce cell death, and activate the expression of genes involved in salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) signaling pathways. Furthermore, the GH12 domain (position 43–249) was sufficient for cell death-inducing activity, rather than the CBM1 domain. Additionally, the leucine-rich repeat (LRR) receptor-like kinases NbBAK1 and NbSOBIR1 were required for defense responses triggered by CcEG1. Intriguingly, deletion of CcEG1 did not affect fungal pathogenicity, growth, response to hydrogen peroxide and cell wall integrity agents, but affected cellulase utilization. In conclusion, our results suggest that CcEG1 induces coreceptors NbBAK1- and NbSOBIR1- dependent plant immunity, increasing our understanding about fungal pathogenesis during the interaction between C. chrysosperma and its host.

Abstract Machine learning is widely used to infer ground-level concentrations of air pollutants from satellite observations. However, a single pollutant is commonly targeted in previous explorations, which would lead to duplication of efforts and ignoration of interactions considering the interactive nature of air pollutants and their common influencing factors. We aim to build a unified model to offer a synchronized estimation of ground-level air pollution levels. We constructed a multi-output random forest (MORF) model and achieved simultaneous estimation of hourly concentrations of PM2.5, PM10, O3, NO2, CO, and SO2 in China, benefiting from the world’s first geostationary air-quality monitoring instrument Geostationary Environment Monitoring Spectrometer. MORF yielded a high accuracy with cross-validated R2 reaching 0.94. Meanwhile, model efficiency was significantly improved compared to single-output models. Based on retrieved results, the spatial distributions, seasonality, and diurnal variations of six air pollutants were analyzed and two typical pollution events were tracked.

Serial correlations within temperature time series serve as indicators of the temporal consistency of climate events. This study delves into the serial correlations embedded in global surface air temperature (SAT) data. Initially, we preprocess the SAT time series to eradicate seasonal patterns and linear trends, resulting in the SAT anomaly time series, which encapsulates the inherent variability of Earth's climate system. Employing diverse statistical techniques, we identify three distinct types of serial correlations: short-term, long-term, and nonlinear. To identify short-term correlations, we utilize the first-order autoregressive model, AR(1), revealing a global pattern that can be partially attributed to atmospheric Rossby waves in extratropical regions and the Eastern Pacific warm pool. For long-term correlations, we adopt the standard detrended fluctuation analysis, finding that the global pattern aligns with long-term climate variability, such as the El Niño-Southern Oscillation (ENSO) over the Eastern Pacific. Furthermore, we apply the horizontal visibility graph (HVG) algorithm to transform the SAT anomaly time series into complex networks. The topological parameters of these networks aptly capture the long-term correlations present in the data. Additionally, we introduce a novel topological parameter, Δσ, to detect nonlinear correlations. The statistical significance of this parameter is rigorously tested using the Monte Carlo method, simulating fractional Brownian motion and fractional Gaussian noise processes with a predefined DFA exponent to estimate confidence intervals. In conclusion, serial correlations are universal in global SAT time series and the presence of these serial correlations should be considered carefully in climate sciences.

Pancreatic cancer is a leading cause of cancer-related deaths worldwide. Conventional therapies often provide limited success, necessitating the need for novel therapeutic strategies. Oncolytic viruses (OVs) are a class of viruses that specifically target and kill cancer cells while leaving normal cells unharmed. These viruses have shown promise in the treatment of various cancers, including pancreatic cancer. However, their use in clinical settings has been limited by several factors. Their inability to efficiently infect and kill tumor cells. To overcome this limitation, a cell membrane-coated oncolytic virus was developed. However, the necessity of homologous and nonhomologous tumor cell membranes for their function has not yet been proven. This novel virus displayed increased infectivity and killing activity against tumor cells compared to nonhomologous tumor cell membranes and noncoated viruses. We believe that the homologous tumor cell membranes-coated OVs can enhance the therapeutic potential for pancreatic cancer therapy.

Background: Evidence suggests that maternal exposure to heat might increase the risk of preterm birth (PTB), but no study has investigated the effect from urban heat island (UHI) at individual level. Aims: Our study aimed to investigate the association between individual UHI exposure and PTB. Methods: We utilized data from the ongoing China Birth Cohort Study (CBCS), encompassing 103,040 birth records up to December 2020. UHI exposure was estimated for each participant using a novel individual assessment method based on temperature data and satellite-derived land cover data. We used generalized linear mixed-effects models to estimate the association between UHI exposure and PTB, adjusting for potential confounders including maternal characteristics and environmental factors. Results: Consistent and statistically significant associations between UHI exposure and PTB were observed up to 21 days before birth. A 5 °C increment in UHI exposure was associated with 27 % higher risk (OR = 1.27, 95 % confident interval: 1.20, 1.34) of preterm birth in lagged day 1. Stratified analysis indicated that the associations were more pronounced in participants who were older, had higher pre-pregnancy body mass index level, of higher socioeconomic status and living in greener areas. Conclusion: Maternal exposure to UHI was associated with increased risk of PTB. These findings have implications for developing targeted interventions for susceptible subgroups of pregnant women. More research is needed to validate our findings of increased risk of preterm birth due to UHI exposure among pregnant women.

Human Action Recognition (HAR) is an essential topic in computer vision and artificial intelligence, focused on the automatic identification and categorization of human actions or activities from video sequences or sensor data. The goal of HAR is to teach machines to comprehend and interpret human movements, gestures, and behaviors, allowing for a wide range of applications in areas such as surveillance, healthcare, sports analysis, and human-computer interaction. HAR systems utilize a variety of techniques, including deep learning, motion analysis, and feature extraction, to capture and analyze the spatiotemporal characteristics of human actions. These systems have the capacity to distinguish between various actions, whether they are simple actions like walking and waving or more complex activities such as playing a musical instrument or performing sports maneuvers. HAR continues to be an active area of research and development, with the potential to enhance numerous real-world applications by providing machines with the ability to understand and respond to human actions effectively. In our study, we developed a HAR system to recognize actions in tennis using an attention-based gated recurrent unit (GRU), a prevalent recurrent neural network. The combination of GRU architecture and attention mechanism showed a significant improvement in prediction power compared to two other deep learning models. Our models were trained on the THETIS dataset, one of the standard medium-sized datasets for fine-grained tennis actions. The effectiveness of the proposed model was confirmed by three different types of image encoders: InceptionV3, DenseNet, and EfficientNetB5. The models developed with InceptionV3, DenseNet, and EfficientNetB5 achieved average ROC-AUC values of 0.97, 0.98, and 0.81, respectively. While, the models obtained average PR-AUC values of 0.84, 0.87, and 0.49 for InceptionV3, DenseNet, and EfficientNetB5 features, respectively. The experimental results confirmed the applicability of our proposed method in recognizing action in tennis and may be applied to other HAR problems.

Abstract Background Toxoplasma gondii is an obligate intracellular apicomplexan parasite and is responsible for zoonotic toxoplasmosis. It is essential to develop an effective anti-T. gondii vaccine for the control of toxoplasmosis, and this study is to explore the immunoprotective effects of a live attenuated vaccine in mice and cats. Methods First, the ompdc and uprt genes of T. gondii were deleted through the CRISPR-Cas9 system. Then, the intracellular proliferation and virulence of this mutant strain were evaluated. Subsequently, the immune responses induced by this mutant in mice and cats were detected, including antibody titers, cytokine levels, and subsets of T lymphocytes. Finally, the immunoprotective effects were evaluated by challenge with tachyzoites of different strains in mice or cysts of the ME49 strain in cats. Furthermore, to discover the effective immune element against toxoplasmosis, passive immunizations were carried out. GraphPad Prism software was used to conduct the log-rank (Mantel–Cox) test, Student’s t test and one-way ANOVA. Results The RHΔompdcΔuprt were constructed by the CRISPR-Cas9 system. Compared with the wild-type strain, the mutant notably reduced proliferation (P

Abstract Previous studies have shown the potential of immunogenic cell death-related modalities in myeloma. The significance of IL5RA in myeloma and immunogenic cell death remains unknown. We analyzed IL5RA expression, the gene expression profile, and secretory protein genes related to IL5RA level using GEO data. Immunogenic cell death subgroup classification was performed using the ConsensusClusterPlus and pheatmap R package. Enrichment analyses were based on GO/KEGG analysis. After IL5RA-shRNA transfection in myeloma cells, cell proliferation, apoptosis, and drug sensitivity were detected. P

Abstract Background and Objective Abiraterone acetate tablet is an inhibitor of androgen synthesis, primarily for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluated the bioequivalence and pharmacokinetics of the reference and test formulations of abiraterone acetate tablets in healthy Chinese volunteers. Methods A single-center, open, single-dose, randomized, three-period, three-sequence, semi-repeat (only repeated reference formulations), and reference formulation-corrected fasting reference-scaled average bioequivalence test was conducted in 36 healthy volunteers included in this study. Volunteers were randomly assigned to one of three groups in a 1:1:1 ratio. There was a minimum 7-day washout period between each dose. Blood samples were collected at prescribed time intervals, the plasma concentration of abiraterone acetate tablets was determined by liquid chromatography-tandem mass spectrometry, and adverse events were recorded. Results Under fasting conditions, the maximum plasma concentration (C max) was 27.02 ± 14.21 ng/mL, area under the concentration-time curve from time zero to time t (AUC t ) was 125.30 ± 82.41 h·ng/mL, and AUC from time zero to infinity (AUC ∞ ) was 133.70 ± 83.99 h·ng/mL. The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of AUC t and AUC ∞ were in the range of 0.8000–1.2500, and the coefficient of variation (CVWR) of C max was more than 30%. The Critbound result was − 0.0522, and the GMR was between 0.8000 and 1.2500. Conclusion Both test and reference formulations of abiraterone acetate tablets were bioequivalent in healthy Chinese subjects under fasting conditions. Trial registration ClinicalTrials.gov identifier NCT04863105, registered 26 April 2021—retrospectively registered ( https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000ARAA&selectaction=Edit&uid=U00050YQ&ts=2&cx=-vbtjri

Abstract Methane (CH4) is the second most potent greenhouse gas (GHG), and China emerges as the largest anthropogenic CH4 emitter by country. Current limited CH4 monitoring systems in China are unfortunately inadequate to support carbon management. Here we use the Weather Research and Forecasting model (WRF) coupled with a GHG module and satellite constrained emissions to simulate the spatiotemporal distribution of CH4 over East Asia in 2017. Model evaluations using both satellite retrievals and ground-based observations indicate reliable performance. We further inter-compare four proper orthogonal decomposition (POD)-based sensor placement algorithms and find they are able to capture main spatial features of surface CH4 under an oversampled condition. The QR pivot algorithm exhibits superiority in capturing high CH4, and it offers the best reconstruction with both high efficiency and accuracy. Areas with high CH4 concentrations and intense anthropogenic activities remain underrepresented by current CH4 sampling studies, leading to notable reconstruction error over central and eastern China. Optimal planning of 160 sensors guided by the QR pivot algorithm can yield reasonable reconstruction performance and costs of site construction. Our results can provide valuable references for future planning of CH4 monitoring sites.

Abstract Background Self-sampling HPV test and thermal ablation are effective tools to increase screening coverage and treatment compliance for accelerating cervical cancer elimination. We assessed the cost-effectiveness of their combined strategies to inform accessible, affordable, and acceptable cervical cancer prevention strategies. Methods We developed a hybrid model to evaluate costs, health outcomes, and incremental cost-effectiveness ratios (ICER) of six screen-and-treat strategies combining HPV testing (self-sampling or physician-sampling), triage modalities (HPV genotyping, colposcopy or none) and thermal ablation, from a societal perspective. A designated initial cohort of 100,000 females born in 2015 was considered. Strategies with an ICER less than the Chinese gross domestic product (GDP) per capita ($10,350) were considered highly cost-effective. Results Compared with current strategies in China (physician-HPV with genotype or cytology triage), all screen-and-treat strategies are cost-effective and self-HPV without triage is optimal with the most incremental quality-adjusted life-years (QALYs) gained (220 to 440) in rural and urban China. Each screen-and-treat strategy based on self-collected samples is cost-saving compared with current strategies (−$818,430 to −$3540) whereas more costs are incurred using physician-collected samples compared with current physician-HPV with genotype triage (+$20,840 to +$182,840). For screen-and-treat strategies without triage, more costs (+$9404 to +$380,217) would be invested in the screening and treatment of precancerous lesions rather than the cancer treatment compared with the current screening strategies. Notably, however, more than 81.6% of HPV-positive women would be overtreated. If triaged with HPV 7 types or HPV16/18 genotypes, 79.1% or 67.2% (respectively) of HPV-positive women would be overtreated with fewer cancer cases avoided (19 cases or 69 cases). Conclusions Screen-and-treat strategy using self-sampling HPV test linked to thermal ablation could be the most cost-effective for cervical cancer prevention in China. Additional triage with quality-assured performance could reduce overtreatment and remains highly cost-effective compared with current strategies.

With the increasingly fierce market competition, customers’ needs are gradually becoming more complicated, specialized, customized, and personalized. How manufacturing enterprises adopt innovation strategies to achieve value-added products as well as value co-creation with customers is an important initiative for enterprises to maintain differentiated advantages in market competition. Therefore, the creation of service value has gradually become more and more important. The related research on manufacturing servitization has attracted extensive attention in recent years. Manufacturing servitization is the evolution process of manufacturing enterprises gradually from product-dominant logic to service-dominant logic. The purpose of this study is to explore the dynamic evolution of manufacturing servitization from the perspective of innovation strategy and analyze the dynamic evolution mechanism. This study shows the latest research progress of theories related to manufacturing servitization and lays the theoretical foundation for research on the mechanism of the dynamic evolution of manufacturing servitization. This study proposes a three-stage dynamic evolution model of manufacturing servitization: product production, technological innovation, and service innovation. This study primarily employs the research methods of model construction and computer simulation. Based on the Nelson–Winter model, this study establishes a decision model for manufacturing servitization innovation strategy. This study conducts a computer simulation study on the dynamic evolution of manufacturing servitization from the perspective of innovation strategy and draws conclusions. This study is of great significance for manufacturing enterprises in making appropriate service-oriented innovation strategy decisions in the context of the service-oriented transformation occurring widely in the manufacturing industry.

Pine wood nematode disease, commonly referred to as pine wilt, poses a grave threat to forest health, leading to profound ecological and economic impacts. Originating from the pine wood nematode, this disease not only causes the demise of pine trees but also casts a long shadow over the entire forest ecosystem. The accurate identification of infected trees stands as a pivotal initial step in developing effective prevention and control measures for pine wilt. Nevertheless, existing identification methods face challenges in precisely determining the disease status of individual pine trees, impeding early detection and efficient intervention. In this study, we leverage the capabilities of unmanned aerial vehicle (UAV) remote sensing technology and integrate the VGG classical small convolutional kernel network with U-Net to detect diseased pine trees. This cutting-edge approach captures the spatial and characteristic intricacies of infected trees, converting them into high-dimensional features through multiple convolutions within the VGG network. This method significantly reduces the parameter count while enhancing the sensing range. The results obtained from our validation set are remarkably promising, achieving a Mean Intersection over Union (MIoU) of 81.62%, a Mean Pixel Accuracy (MPA) of 85.13%, an Accuracy of 99.13%, and an F1 Score of 88.50%. These figures surpass those obtained using other methods such as ResNet50 and DeepLab v3+. The methodology presented in this research facilitates rapid and accurate monitoring of pine trees infected with nematodes, offering invaluable technical assistance in the prevention and management of pine wilt disease.

Leveraging data from various modalities to enhance multimodal segmentation tasks is a well-regarded approach. Recently, efforts have been made to incorporate an array of modalities, including depth and thermal imaging. Nevertheless, the effective amalgamation of cross-modal interactions remains a challenge, given the unique traits each modality presents. In our current research, we introduce the semantic guidance fusion network (SGFN), which is an innovative cross-modal fusion network adept at integrating a diverse set of modalities. Particularly, the SGFN features a semantic guidance module (SGM) engineered to boost bi-modal feature extraction. It encompasses a learnable semantic guidance convolution (SGC) designed to merge intensity and gradient data from disparate modalities. Comprehensive experiments carried out on the NYU Depth V2, SUN-RGBD, Cityscapes, MFNet, and ZJU datasets underscore both the superior performance and generalization ability of the SGFN compared to the current leading models. Moreover, when tested on the DELIVER dataset, the efficiency of our bi-modal SGFN displayed a mIoU that is comparable to the hitherto leading model, CMNEXT.

The significance of radiation shielding is on the rise due to the expanding areas exposed to radiation emissions. Consequently, there is a critical need to develop metal alloys and composites that exhibit excellent capabilities in absorbing neutron and gamma rays for effective radiation shielding. Low-density Ti-based alloys with controlled structural properties can be used for radiation protection purposes. The present research investigates boron-doped Ti-based alloy, Ti50Cu30Zr15B5, which is synthesized by arc melting technique, and its structural, mechanical properties, neutron, and gamma-ray transmission rate were investigated. Monte Carlo N-Particle simulation (MCNP6.2) code is used for calculating the Thermal (2.53 × 10−8 MeV) and fast (2 MeV) neutron transmission ratio (I/I0) dependent on the sample thickness. The Phy-x program is employed for calculating the gamma-ray LAC, MAC, HVL, TVL, and MFP values. The calculated neutron shielding performance parameters of Ti50Cu30Zr15B5 alloy were compared with materials in the literature. It was found that Ti50Cu30Zr15B5 alloy demonstrated impressive physical characteristics, suggesting that it can serve as a promising alloy for neutron and gamma-ray shielding applications.

Under global warming and rapid urbanization, heat extremes, ozone pollution, and their co-occurrences are emerging and posing severe risks to human health. However, possibly different characteristics of independent heat days (IHD), independent ozone pollution (IOP) and compound heat-ozone pollution (CHOP) events are unclear. In this study, we present an investigation of the spatial distribution and mechanisms associated with IHD, IOP and CHOP events during May–October in 2014–2022 by taking the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) of China as an example. The results show that central GBA faces higher compound risk than northwestern and southeastern regions. IHD events are primarily driven by extremely high temperatures and accompanied by anomalous anticyclone and high pressure at both lower and upper troposphere levels, under the joint effects of the South Asian high and western North Pacific subtropical high. IOP events are predominantly accompanied by decreased cloud cover, air humidity and enhanced downward solar radiation. CHOP events are influenced by increases in both temperature and downward solar radiation. The circulation patterns of CHOP events are somewhat similar to IOP but with much stronger magnitude and faster developing process, and both are likely related to tropical cyclone activities. Our findings can strengthen the early forecasting of these extreme events and mitigate their negative impacts.

As a new generation of necessary terminals for future homes, smart homes have become one of the essential mediums for smart aging at home. This paper aims to explore how older adults who age at home can overcome the digital divide of the new medium and achieve social participation in the home context to realize active aging. Based on the theory of social compensation, we select the smart-home smart screen, a representative new medium product in China, and carry out open coding, spindle coding, selective coding, and theoretical construction of the original interview data through the grounded theory research method. The results show that the main factors affecting the social compensation of older adults to smart home social media include user interface quality, interaction quality, content quality, and service quality, and these four factors are used as external variables to compensate older adults socially, thereby stimulating the emotional experience and perception changes at the cognitive level of older adults and then affecting the adoption and acceptance of smart home social media by older adults. This study refines the factors influencing the older adults’ use of smart home social media from the perspective of social compensation. It explains the mechanism of acceptable behavior of older adults, bridging the gap in previous literature on the influencing factors and behavioral mechanisms of older adults of smart home social media. This paper provides a theoretical basis and guidance for the subsequent academic research and software development practice of social media under new technological devices to further help older adults in China achieve active and healthy aging.

BackgroundThe purpose of this study was to investigate the correlation between serum 25(OH)D concentrations and all-cause mortality in patients with kidney stone disease (KSD) as the effects of a deficiency in 25-hydroxyvitamin D on KSD patients are currently unclear.MethodsFor our prospective cohort study, we included 2,916 participants from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. The National Death Index (NDI) was utilized to identify all causes of death and cause-specific mortality until December 31, 2018. We calculated hazard ratios (HR) and 95% confidence intervals (CIs) using multivariate Cox regression models.ResultsDuring the 18,859 person-years of follow-up, a total of 375 fatalities occurred, including 83 deaths from cardiovascular disease (CVD) and 79 deaths from cancer. At baseline, individuals with higher blood 25(OH)D concentrations had lower levels of glucose, glycohemoglobin, CRP, and insulin, as well as higher levels of HDL cholesterol (P < 0.01). In the fully adjusted model (Model 3), compared to the group with the lowest 25(OH)D concentrations, those with serum 25(OH)D concentrations ≥75 nmol/L had hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.48 (0.26, 0.87) for all-cause mortality (P=0.02, P for trend = 0.02). The association between serum 25(OH)D concentrations and all-cause mortality in KSD patients was found to be significantly non-linear. A 7% decrease in the risk of death from all causes was observed for each unit-nmol/L increase in serum 25(OH)D concentrations when the concentrations were below 27.7 nmol/L (P < 0.05).ConclusionBased on the findings, KSD patients with insufficient serum 25(OH)D concentrations were at a higher risk of all-cause mortality. Therefore, it is crucial to maintain sufficient blood 25(OH)D concentrations and prevent 25(OH)D insufficiency in order to extend the lifespan of KSD patients.

Abstract Flexible Zn–air batteries (FZABs) exhibit low cost and inherent safety and have potential for application in wearable electronic devices. Nevertheless, balancing the high energy density and flexibility of the self-supported electrodes in FZABs is still a challenge. Herein, we develop a novel superassembly strategy for the preparation of N, S-codoped porous carbon frameworks (NS@CFs) as cathodes in FZABs. Benefiting from the abundant heteroatom defect sites, NS@CF exhibits excellent electrocatalytic performance for the oxygen reduction reaction (ORR), including high electrochemical activity and long-term stability. When used as the cathode in a liquid flowing ZAB, NS@CF exhibited a power density of 221 mW cm−2 and achieved a 60% improvement over Pt/C-based ZABs. This new ZAB exhibited a high specific capacity of 792 mA h gZn −1, excellent long-term durability and cycling stability, which is superior to those of ZABs assembled with commercial Pt/C cathodes. In addition, the flexible NS@CF with directional channels can be used as independent air cathodes for FZABs, where it provides small charge/discharge voltage gaps, a power density of 49 mW cm−2 and outstanding cycling stability. This work provides a novel strategy for designing and fabricating highly efficient integrated electrodes for flexible and wearable electrochemical devices.

Crocosphaera and Cyanothece are both unicellular, nitrogen-fixing cyanobacteria that prefer different environments. Whereas Crocosphaera mainly lives in nutrient-deplete, open oceans, Cyanothece is more common in coastal, nutrient-rich regions. Despite their physiological similarities, the factors separating their niches remain elusive. Here we performed physiological experiments on clone cultures and expand upon a simple ecological model to show that their different niches can be sufficiently explained by the observed differences in their photosynthetic capacities and rates of carbon (C) consumption. Our experiments revealed that Cyanothece has overall higher photosynthesis and respiration rates than Crocosphaera. A simple growth model of these microorganisms suggests that C storage and consumption are previously under-appreciated factors when evaluating the occupation of niches by different marine nitrogen fixers.

Abstract 4-Androstene-3,17-dione (4-AD) and 22-hydroxy-23,24-bisnorchol-4-ene-3-one (BA) are the most important and representative C19- and C22-steroidal materials. The optimalization of sterol production with mycobacterial phytosterol conversion has been investigated for decades. One of the major challenges is that current industrial mycobacterial strains accumulate unignorable impurities analogous to desired sterol intermediates, significantly hampering product extractions and refinements. Previously, we identified Mycobacterium neoaurum HGMS2 as an efficient 4-AD-producing strain (Wang et al. in Microb Cell Fact. 19:187, 2020). Recently, we have genetically modified the HGMS2 strain to remove its major impurities including ADD and 9OH-AD (Li et al. in Microb Cell Fact. 20:158, 2021). Unexpectedly, the modified mutants started to significantly accumulate BA compared with the HGMS2 strain. In this work, while we attempted to block BA occurrence during 4-AD accumulation in HGMS2 mutants, we identified a few loop pathways that regulated metabolic flux switching between 4-AD and BA accumulations and found that both the 4-AD and BA pathways shared a 9,10-secosteroidial route. One of the key enzymes in the loop pathways was Hsd4A1, which played an important role in determining 4-AD accumulation. The inactivation of the hsd4A1 gene significantly blocked the 4-AD metabolic pathway so that the phytosterol degradation pathway flowed to the BA metabolic pathway, suggesting that the BA metabolic pathway is a complementary pathway to the 4-AD pathway. Thus, knocking out the hsd4A1 gene essentially made the HGMS2 mutant (HGMS2 Δhsd4A1 ) start to efficiently accumulate BA. After further knocking out the endogenous kstd and ksh genes, an HGMS2 Δhsd4A1 mutant, HGMS2 Δhsd4A1/Δkstd1 , enhanced the phytosterol conversion rate to BA in 1.2-fold compared with the HGMS2 Δhsd4A1 mutant in pilot-scale fermentation. The final BA yield increased to 38.3 g/L starting with 80 g/L of phytosterols. Furthermore, we knocked in exogenous active kstd or ksh genes to HGMS2 Δhsd4A1/Δ kstd1 to construct DBA- and 9OH-BA-producing strains. The resultant DBA- and 9OH-BA-producing strains, HGMS2 Δhsd4A1/kstd2 and HGMS2 Δkstd1/Δhsd4A1/kshA1B1 , efficiently converted phytosterols to DBA- and 9OH-BA with the rates of 42.5% and 40.3%, respectively, and their final yields reached 34.2 and 37.3 g/L, respectively, starting with 80 g/L phytosterols. Overall, our study not only provides efficient strains for the industrial production of BA, DBA and 9OH-BA but also provides insights into the metabolic engineering of the HGMS2 strain to produce other important steroidal compounds.

Objective Previous studies on osteoporotic vertebral fractures are usually based on the neutral posture of spine; however, the fractures are usually associated with the flexion posture of spine. Therefore, we aimed to ascertain the relationship between vertebral compression fractures and thoracolumbar hyperflexion Cobb angles (TLHCobb) and determine the clinical cut‐off of the TLHCobb angle. Methods In this retrospective case–control study, TLHCobbs were collected from 154 postmenopausal women (67.45 ± 6.68 years) with vertebral compression fractures (study group) and 310 postmenopausal women (66.57 ± 8.22 years) without vertebral compression fractures (control group) from June 2017 to July 2019. Demographic data, clinical data, and quantitative computed tomography (QCT) findings were compared between the groups. Chi‐squared tests, unpaired t‐tests, and Mann Whitney U were used to assess the group characteristics and proportions. Logistic regression was used to examine the association between vertebral compression fractures and TLHCobb. The cut‐off of the TLHCobb was determined by ROC curve and Youden's index. Results Fracture prevalence was higher in the higher TLHCobb study group than that in the control group [OR = 2.81 (2.15–3.67)] after adjusting for age, BMI, and QCT findings. TLHCobbs at and >20.05° were associated with an increased fracture prevalence and ORs of 2.79 (1.82–4.27) and 4.83 (3.24–7.20), respectively. TLHCobb, disk height (semiquantitative grading score) and QCT values differed between the study and control groups (p 20.05° can be an indicator of vertebral fracture.

Coxsackievirus A16 (CVA16) is one of the major pathogens responsible for human hand, foot, and mouth disease (HFMD), which has threatened the health of young children, particularly in Asia-Pacific nations. Vaccination is an effective strategy for protecting children from CVA16 infection. However, there is currently no licensed CVA16 vaccine for use in humans. In this study, we isolated a high-growth CVA16 virus strain in MRC-5 cells and developed an MRC-5-adapted vaccine candidate strain termed CVA16-393 via two rounds of plaque purification. The CVA16-393 strain was grouped into the B1b subgenotype and grew to a titre of over 107 TCID50/ml in MRC-5 cells. The VP1 gene region of this strain, which contains the major neutralizing epitopes, displayed high stability during serial passages. The inactivated whole-virus vaccine produced by the CVA16-393 strain induced an effective neutralizing antibody response in Meriones unguiculatus (gerbils) after two doses of intraperitoneal inoculation. One week after the booster immunization, the geometric mean titres of the neutralizing antibodies for the 10246, 40812TXT, 11203SD, TJ-224 and CA16-194 strains from different regions of China were 137.8, 97.8, 113.4, 64.1 and 122.3, respectively. A CVA16 vaccine dose above 25 U was also able to provide 100% cross-protection against lethal challenges with these five clinical strains in gerbils. Immunization at a one-week interval could maintain a high level of neutralizing antibody titres for at least 8 weeks. Thus, the vaccine produced by this CVA16-393 strain might be promising.

Abstract Background Adequate sedation is essential for pediatric patients undergoing 3Tesla (T) magnetic resonance imaging (MRI). Using propofol alone is associated with patient arousing and adverse airway events. This study aimed to assess esketamine vs dexmedetomidine adjunct to propofol sedation for pediatric 3 T MRI. Methods In this randomized, double-blind, controlled trial, 114 pediatric patients aged between 6 months and 8 years were randomly assigned, in a 1:1 ratio, to the esketamine–propofol group or the dexmedetomidine–propofol group. Sedation was provided with esketamine or dexmedetomidine in combination with propofol titration. The primary outcome was the total dose of propofol. Secondary outcomes included propofol infusion dose, adverse events, time to emergence from sedation, and time to discharge from recovery room. Results A total of 111 patients completed this study (56 in the esketamine–propofol group and 55 in the dexmedetomidine–propofol group). All MRI procedures were successfully performed under sedation. The total median (IQR) dose of propofol was significantly lower in the esketamine–propofol group (159.8 [121.7, 245.2] μg/kg/min) than that in the dexmedetomidine–propofol group (219.3 [188.6, 314.8] μg/kg/min) (difference in medians [95% CI] = − 66.9 [− 87.8 to − 43.0] μg/kg/min, P

In this paper, a typical teaching building of a university in Urumqi, Xinjiang was taken as the research object. Based on the existing maintenance structure, DesignBuilder software was used to explore the differences in energy consumption and carbon emissions generated by ordinary hot water heating system, ground thermal radiation heating and electric heating under different ventilation times. The effects of intermittent heating and continuous heating on heating energy consumption and carbon emission were studied by software simulation. Conclusion On the condition of ensuring indoor thermal comfort, electric heating is suitable for teaching buildings in Urumqi city, and intermittent heating is not suitable, continuous heating should be used. The heating system with the highest indoor comfort level is the ground heat radiation heating system, and the carbon emission is the ordinary hot water heating system. When the ratio of window and wall area under electric heating increases by 5%, the total heating energy consumption and carbon emission of buildings will increase by 10.8%–16.2% in the heating season, and the heating heat load of buildings will increase by 6.4%–8.2%.