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Abstract Purpose The objective of this study was to evaluate the clinical efficacy of a 4D digital strabismus and amblyopia visual function correction system (4D-DSAAVFCS) in combination with conventional modalities compared with conventional modalities alone in children with anisometropic amblyopia. Methods This nonrandomized controlled study collected data on best-corrected visual acuity (BCVA), simultaneous vision, fusion vision, near stereoscopic vision, the amplitude of P100 wave (graphic evoked visual potentials), and the latency of P100 wave from both eyes at the beginning of the treatment and one year later. The Mann‒Whitney U test was used to compare BCVA contrasts in different subgroups, and the independent samples t test was used to compare the amplitude and latency of P100 wave contrasts in different subgroups. The basic cure rate, simultaneous vision recovery rate, fusion vision recovery rate, and near stereoscopic vision recovery rate contrasts in different subgroups were compared via the chi-square test. Results This study included 393 children (217 boys and 176 girls) aged 3 to 12 years with anisometropic amblyopia who were treated at the Aier Eye Hospital of Wuhan University from January 2020 to December 2022. The children were divided into two groups, the 4D group (263 cases) and the traditional group (130 cases), on the basis of the treatment modality. The children in the traditional group received treatment through the conventional method of occlusion and regular training. Meanwhile, the children in the 4D group received treatment through the traditional method and the 4D-DSAAVFCS. The 4D group was divided into two age groups: 3 ~ 6 years (161 cases) and 6 ~ 12 years (102 cases). The basic cure rate of the 4D group was significantly better than that of the traditional group (χ2 = 4.318, P 0.05 ). After one year of treatment, a statistically significant difference was observed between the 4D group and the conventional group in terms of BCVA, the latency of P100 wave, and the amplitude of P100 wave (U=-1.243, t=-0.853, t=-1.546, all P

Abstract The association between tobacco smoke exposure and sleep has been widely discussed, but the correlation between serum cotinine levels and sleep health outcomes in adolescents has not been well described. This study aimed to further evaluate the association between serum cotinine levels and sleep health outcomes in adolescents using data from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. This cross-sectional study included participants aged 16–19 years from the NHANES 2005–2018. A weighted multivariate logistic regression model was used for the primary analysis. A restricted cubic spline (RCS) model was employed to investigate the non-linear association between serum cotinine levels and trouble sleeping. Subgroup analyses based on population characteristics were also conducted. In total, 2630 participants were included, which are representative of the 11.5 million US adolescents. Higher serum cotinine levels (≥ 3 ng/ml) were significantly associated with trouble sleeping in the fully adjusted model (odds ratio [OR] 1.817). The RCS model revealed a non-linear relationship between serum cotinine levels and trouble sleeping. Subgroup analyses indicated that this relationship was consistent and stable across various population characteristics. Serum cotinine levels are associated with sleep health outcomes in adolescents, with high serum cotinine levels being linked to increased trouble sleeping and longer or shorter sleep duration.

Abstract Rice grown in cadmium (Cd)-contaminated soil, is a potential threat to human health, but exogenous selenium (Se) application on rice can mitigate Cd toxicity. However, the mechanisms underlying Se mitigation of Cd stress in ratoon rice (RR) are still poorly understood. We conducted a pot experiment with moderate Cd-contaminated yellow–brown paddy soil on two rice varieties ‘Taoyouxiangzhan’ (TX) and ‘Liangyou 6326’(LY). For all treatments, 1.0 mg kg−1 sodium selenite solution was added to soil. Treatment T1 was sodium selenite only, and in the other treatments 100 mg L−1 Se solution was sprayed on the leaves at seedling stage (T2), at tillering stage (T3), and in early anthesis stage (T4). Se treatments decreased Cd accumulation in rice grains and herbage. Under foliar spraying 100 mg L−1 Se at the seedling + 1.0 mg kg−1 Se in soil (T2), leaf Cd content decreased 16.95% in the current season and grains content decreased 46.67% in the subsequent season. Furthermore, grain Se content increased 0.94 mg kg−1 for the TX variety combined with the analysis of Cd bio-accumulation factor in grains, and Se treatments effectively decreased Cd grain concentrations due to reduced Cd translocation from roots to grains. TX variety rice showed a more pronounced response to Se treatments than LY.

Abstract The emergence of spatial multi-omics has helped address the limitations of single-cell sequencing, which often leads to the loss of spatial context among cell populations. Integrated analysis of the genome, transcriptome, proteome, metabolome, and epigenome has enhanced our understanding of cell biology and the molecular basis of human diseases. Moreover, this approach offers profound insights into the interactions between intracellular and intercellular molecular mechanisms involved in the development, physiology, and pathogenesis of human diseases. In this comprehensive review, we examine current advancements in multi-omics technologies, focusing on their evolution and refinement over the past decade, including improvements in throughput and resolution, modality integration, and accuracy. We also discuss the pivotal contributions of spatial multi-omics in revealing spatial heterogeneity, constructing detailed spatial atlases, deciphering spatial crosstalk in tumor immunology, and advancing translational research and cancer therapy through precise spatial mapping.

In order to investigate the distribution and accumulation characteristics of metabolites and mineral elements in different parts of Peganum harmala L. (P. harmala), and the synergistic or antagonistic effects between them. In this study, nuclear magnetic resonance (NMR), high performance liquid chromatography (HPLC) and inductively coupled plasma optical emission spectrometer (ICP-OES) were used to determine the contents of metabolites (proline, phosphorylcholine, choline, lysine, 4-hydroxyisoleucine, asparagine, acetic acid, sucrose, harmaline and vasicine) and mineral elements (Ca, Mg, K, P, Na, Cr, Cu, Fe, Zn, Mn, Ni, C, N) in five parts of P. harmala, including root, seed, testa, stem and leaf, and to analyze the relationship among the contents of metabolites and mineral elements. The results showed that the contents of acetic acid, proline, lysine, sucrose and Fe in the root were higher than those in other parts, and the contents of harmaline, phosphorylcholine, P, C, N and Zn in the seeds were the highest. The leaves were rich in vasicine, Na, K, Ca, Mg and Mn. The principal component analysis (PCA) showed that the cumulative variance contribution of the first two principal components was 69.00 %, and the loading values of K, Cu and sucrose were higher, which was consistent with the results of biplot and cluster analysis(HCA). Correlation analysis (CA) results showed that there was a strong overall correlation between the different components of seeds and leaves, and the correlation was greater than that of other parts. The results of this study are helpful to understand the correlation of functional traits among different parts of plants, and determine the internal mechanism of controlling functional traits and the proportional relationship between traits, so as to provide a reference for the resource utilization of plants.

Abstract Nucleolar protein 12 (NOL12), one of the nucleolar proteins which are primarily expressed in the nucleolus and play key roles in RNA metabolism, cell proliferation, cell cycle, and cell survival, is widely expressed in various species and multiple organs. Although it has been reported that the mRNA of Drosophila NOL12 homolog viriato is expressed in the eyes of Drosophila, the protein expression of NOL12 in mammalian eyes remains to be elucidated. In this study, we showed through immunohistochemistry that NOL12 was present in the rat retina, with predominant distribution in the cytoplasm of the retinal neuronal cells. In the human retinoblastoma cell line WERI-Rb1, we found that altering NOL12 expression led to a change in WERI-Rb1 cell viability. Knocking down NOL12 expression decreased cell viability. In contrast, overexpressing NOL12 increased cell viability. Furthermore, increasing NOL12 expression inhibited ultraviolet (UV)-induced apoptosis. These findings demonstrated that NOL12 may play an important protective role in retinal cells. In the WERI-Rb1 cells exposed to UV irradiation, we detected that NOL12 was degraded, but this degradation could be attenuated by a pan-Caspase inhibitor. Notably, the inhibitory effect of NOL12 against UV-induced apoptosis could be restrained by increasing the expression of ATR serine/threonine kinase (ATR), a kinase that, when activated by severe DNA damage, can result in apoptosis. We also found that upregulating NOL12 inhibited the activation of ATR caused by UV irradiation. Additionally, inhibiting ATR activity reduced apoptosis resulting from both silencing NOL12 expression and UV exposure. Thus, NOL12 may protect against UV irradiation-induced retinal damage by inhibiting ATR activity.

Renal fibrosis, a critical factor in the development of chronic kidney disease (CKD), is predominantly initiated by acute kidney injury (AKI) and subsequent maladaptive repair resulting from pharmacological or pathological stimuli. Phosphatase and tensin homolog (PTEN), also known as phosphatase and tensin-associated phosphatase, plays a pivotal role in regulating the physiological behavior of renal tubular epithelial cells, glomeruli, and renal interstitial cells, thereby preserving the homeostasis of renal structure and function. It significantly impacts cell proliferation, apoptosis, fibrosis, and mitochondrial energy metabolism during AKI-to-CKD transition. Despite gradual elucidation of PTEN’s involvement in various kidney injuries, its specific role in AKI and maladaptive repair after injury remains unclear. This review endeavors to delineate the multifaceted role of PTEN in renal pathology during AKI and CKD progression along with its underlying mechanisms, emphasizing its influence on oxidative stress, autophagy, non-coding RNA-mediated recruitment and activation of immune cells as well as renal fibrosis. Furthermore, we summarize prospective therapeutic targeting strategies for AKI and CKD-treatment related diseases through modulation of PTEN.

Cordyceps militaris, also called as bei-chong-cao, is an insect-pathogenic fungus from the Ascomycota phylum and the Clavicipitaceae family. It is a valuable filamentous fungus with medicinal and edible properties that has been utilized in traditional Chinese medicine (TCM) and as a nutritious food. Cordycepin is the bioactive compound firstly isolated from C. militaris and has a variety of nutraceutical and health-promoting properties, making it widely employed in nutraceutical and pharmaceutical fields. Due to the low composition and paucity of wild resources, its availability from natural sources is limited. With the elucidation of the cordycepin biosynthetic pathway and the advent of synthetic biology, a green cordycepin biosynthesis in Saccharomyces cerevisiae and Metarhizium robertsii has been developed, indicating a potential sustainable production method of cordycepin. Given that, this review primarily focused on the metabolic engineering and heterologous biosynthesis strategies of cordycepin.

Abstract WRKY transcription factors are pivotal regulators in various aspects of plant biology, including growth, development, secondary metabolic biosynthesis, and responses to both biotic and abiotic stresses. The legume plant Grona styracifolia is widely utilized for its medicinal properties in treating urinary calculi and combating SARS-CoV-2, owing to its bioactive component schaftoside. However, the regulatory function of GsWRKYs in schaftoside biosynthesis within G. styracifolia remains elusive. In the G. styracifolia genome, we identified a total of 102 GsWRKYs, classified phylogenetically into Group I (18), II (68), and III (16). Genomic analysis revealed an uneven distribution of GsWRKYs on chromosomes (Chr), with prevalence on Chr 1, followed by Chr 2, 3, 5, and 6. Among the 82 duplicated GsWRKYs, comprising 12, 54, and 16 members in Group I, II, and III respectively, 11 GsWRKYs were tandemly duplicated genes located across Chr 2 (2), Chr 5 (7), and Chr 9 (2). Weighted gene co-expression network analysis unveiled that 2 Group I (GsWRKY44 and GsWRKY95) and 14 Group II GsWRKYs, including two pairs of segmentally duplicated Group II GsWRKYs associated with thermomorphogenesis, exhibited coexpression with Grona styracifolia C-glycosyltransferases (GsCGT), a gene encoding a C-glucosyltransferase involved in schaftoside biosynthesis. Furthermore, GsWRKY95 demonstrated coexpression with other schaftoside biosynthetic genes. Dual-luciferase and yeast one-hybrid assays provided additional evidence that GsWRKY95 binds to the W-box of GsCGT, activating its expression. In addition, GsWRKY95- and GsCGT-coexpressing G r o na styracifolia chalcone synthase (GsCHSs), along with 11 pairs of segmentally duplicated Group II GsWRKYs, responded to both abiotic and biotic stresses. Notably, certain GsWRKYs were identified as regulators specific to schaftoside biosynthesis in stems, roots, and leaves. These findings suggest that duplication events, particularly in segmentally duplicated Group II GsWRKYs, play a pivotal role in orchestrating the hierarchical regulation of schaftoside biosynthesis. Overall, our results establish a foundation for genetically enhancing G. styracifolia to abundantly produce schaftoside, thereby contributing to its medicinal efficacy.

Rural household energy transition from biomass energy to modern energy is essential for poverty alleviation and sustainable development. Existing studies have explored the determinants of rural household energy transition, but few of them consider household energy availability for modern energy, which is crucial for rural household energy consumption especially in energy poverty areas such as the Tibetan Plateau. This study establishes an analytical framework for exploring the determinants of rural household energy transition by considering household energy availability and household characteristics. By employing the Tobit model, the empirical analysis of Pumqu River Basin (PRB) of the Tibetan Plateau is conducted. The results show that (1) biomass energy is still the dominant energy source in the PRB, with 99.27% of users and 90.77% of rural household energy consumption. (2) The limited energy accessibility in the PRB plays a significant negative role in accelerating rural household energy transition. (3) Educational level of householder, per capita living space, the number of rural household appliances, and community organizations are the drivers for rural household energy transition, whereas per capita livestock number and per capita grassland areas are the constraints. The findings of this study can help decision makers formulate effective measures to promote rural household energy transition in energy poverty area. The framework introduced can be extended for application to examine the determinants of rural household energy transition in other regions.

Allium wallichii Kunth is a herb species with potentially extensive applications because of its edible, ornamental, and pharmaceutical values. The structural characteristics and phylogenetic relationships of its chloroplast genome were determined here for the first time. The complete cp genome was found to be 152,496 bp long, with a GC content of 37.04%. It consists of four distinct regions: a large single copy (LSC) region of 82,510 bp, a small single copy (SSC) region of 17,460 bp, and two inverted repeat (IR) regions of 26,263 bp each. The genome encodes 129 genes, including 86 protein-coding genes, 37 tRNA genes, and six rRNA genes. Our phylogenetic analysis revealed that A. wallichii was closely related to Allium wallichii var. platyphyllum, which are included in the section Bromatorrhiza, subgenus Amerallium Traub of the genus Allium. Our report provides valuable information on the genetic diversity of Allium species.

Abstract Traffic prediction is an important part of intelligent transportation system. Recently, graph convolution network (GCN) is introduced for traffic flow forecasting and achieves good performance due to its superiority of representing the graph traffic road structure network. Moreover, the dynamic GCN is put forward to model the temporal property of the traffic flow. Although great progress has been made, most GCN based traffic flow forecasting methods utilize a single graph for convolution, which is considered not enough to reveal the inherent property of traffic graph as it is influenced by many factors, for example weather, season and traffic accidents etc. In this paper, an exotic graph transformer based dynamic multiple graph convolution networks (GTDMGCN) is conceived for traffic flow forecasting. Instead of the single graph, multiple graphs are constructed to modulate the complex traffic network by the proposed graph transformer network. Additionally, a temporal gate convolution is proposed to get the temporal property of traffic flow. The proposed GTDMGCN model is evaluated on four real traffic datasets of PEMS03, PEMS04, PEMS07, PEMS08, and there are average increments of 9.78%, 7.80%, 5.96% under MAE, RMSE, and MAPE metrics compared with the current results.

Licorice (Glycyrrhiza uralensis Fisch), a significant traditional Chinese herbal medicine, has been extensively utilized in China to treat various ailments. Natural bioactive coumarins, glycycoumarin, glycyrin, and 3-O-methylglycyrol, were isolated from licorice, and they exhibited various pharmacological properties. In this report, we have accomplished the total synthesis of glycycoumarin, glycyrin, and 3-O-methylglycyrol in 5–7 linear steps from commercially available 2,4,6-trihydroxybenzaldehyde with yields of 12.3–21.2%. Additionally, their anti-inflammatory activities were studied and compared. Glycycoumarin, glycyrin, and 3-O-methylglycyrol exhibited different levels of anti-inflammatory activities, with glycyrin being the most potent. Mechanistic studies indicated that glycyrin exerted its anti-inflammatory properties by inhibiting the activation of TNF-α, IL-6, and IL-1β, making it a potential anti-inflammatory lead compound for further optimization and discovery of new agents.

Abstract Background Folic acid (FA) supplementation is associated with a lower risk of the neural tube and heart defects and is recommended for women of childbearing age. Although there are detailed recommendations, differences in the initiation time and duration of FA supplementation remain poorly studied. Methods A multicentre prospective study of 17,713 women was conducted. The incidence of congenital malformations in women taking a recommended dosage (e.g. 0.4 or 0.8 mg/day) of FA was compared with that in women without supplementation. The predicted probability of malformations by the initiation time and duration of FA use was estimated to determine optimal options. Results Periconceptional FA supplementation was associated with a lower and insignificant risk of congenital malformations (1.59% vs. 2.37%; odds ratio [OR] 0.69; 95% confidence interval [CI]: 0.44–1.08), heart defects (3.8 vs. 8.0 per 1000 infants; OR, 0.47; 0.21–1.02), and neural tube defects (7.0 vs. 11.5 per 10,000 infants; OR, 0.64; 0.08–5.15). FA use after pregnancy provided greater protection against total malformations. Statistically significant associations were found in women who initiated FA supplementation in the first month of gestation (OR, 0.55; 95% CI: 0.33–0.91) and in those who supplemented for 1 to 2 months (OR, 0.59; 95% CI: 0.36–0.98). Similar results were found for heart defects. The optimal initiation time was 1.5 (optimal range: 1.1 to 1.9) months before pregnancy and a duration of 4.0 (3.7 to 4.4) months was reasonable to achieve the lowest risk of congenital malformations. Heart defect prevention required an earlier initiation (2.2 vs. 1.1 months before pregnancy) and a longer duration (4.7 vs. 3.7 months) than the prevention of other malformations. Conclusions The timely initiation of FA supplementation for gestation was associated with a decreased risk of congenital malformations, which was mainly attributed to its protection against heart defects. The initiation of FA supplementation 1.5 months before conception with a duration of 4 months is the preferred option for congenital malformation prevention. Trial registration Chictr.org.cn identifier: ChiCTR-SOC-17010976.

Abstract Background Salicylic Acid (SA) is a pivotal phytohormone in plant innate immunity enhancement of triggered by various pathogens, such as Candidatus Liberibacter asiaticus (CLas), the causal agent of Huanglongbing (HLB). WRKY is a plant specific transcription factor (TF) family, which plays crucial roles in plant response to biotic stresses. So far, the evolutionary history, functions, and expression patterns under SA treatment and CLas infection of WRKY family are poorly understood in Citrus, despite the release of the genome of several Citrus species. A comprehensive genomic and expressional analysis is worth to conduct for this family. Results Here, a genome-wide identification of WRKY TFs was performed in two Citrus species: Citrus sinensis (HLB-sensitive) and Poncirus trifoliata (HLB-tolerant). In total, 52 CsWRKYs and 51 PtrWRKYs were identified, whose physical and chemical properties, chromosome locations, phylogenetic relationships and structural characteristics were comparatively analyzed. Especially, expression patterns of these WRKY genes before and after SA treatment and CLas infection were compared. Based on this result, seven pairs of orthologous WRKY genes showing opposite expression patterns in two Citrus species were screened out. Moreover, two pairs of orthologous WRKY genes with significant differences in the number or type of stress-responsive cis-elements in the promoter regions were discovered. Subcellular localization and transcriptional activation activity assays revealed that these two pairs of orthologous genes are classic WRKY TFs localize in the nucleus and could function as transcriptional activators. Conclusion In this study, we systematically analyzed the genomic characterization of WRKY family in two Citrus species, together with the analyses of expression patterns under SA signaling and CLas infection. Our study laid a foundation for further study on the function of WRKY TFs in HLB response and SA signaling of Citrus.

Abstract Background Plant cells usually sustain a stable membrane potential due to influx and/or efflux of charged ions across plasma membrane. With the growth and development of plants, different tissues and cells undergo systemic or local programmed decline. Whether the membrane potential of plasma membrane could report senescence signal of plant tissues and cells is unclear. Results We applied a maneuverable transmembrane potential (TMP) detection method with patch-clamp setup to examine the senescence signal of leaf tissue cells in situ over the whole life cycle in Arabidopsis thaliana. The data showed that the TMPs of plant tissues and cells were varied at different growth stages, and the change of TMP was higher at the vegetative growth stage than at the reproductive stage of plant growth. The distinct change of TMP was detectable between the normal and the senescent tissues and cells in several plant species. Moreover, diverse abiotic stimuli, such as heat stress, hyperpolarized the TMP in a short time, followed by depolarized membrane potential with the senescence occurring. We further examined the TMP of plant chloroplasts, which also indicates the senescence signal in organelles. Conclusions This convenient TMP detection method can report the senescence signal of plant tissues and cells, and can also indicate the potential of plant tolerance to environmental stress.

Astragali radix is a traditional medicinal herb with a long history and wide application. It is frequently used in prescriptions with other medicinal materials to replenish Qi. According to the classics of traditional Chinese medicine, Astragali radix is attributed with properties such as Qi replenishing and surface solidifying, sore healing and muscle generating, and inducing diuresis to reduce edema. Modern pharmacological studies have demonstrated that some extracts and active ingredients in Astragali radix function as antioxidants. The polysaccharides, saponins, and flavonoids in Astragali radix offer beneficial effects in preventing and controlling diseases caused by oxidative stress. However, there is still a lack of comprehensive research on the effective components and molecular mechanisms through which Astragali radix exerts antioxidant activity. In this paper, we review the active components with antioxidant effects in Astragali radix; summarize the content, bioavailability, and antioxidant mechanisms; and offer a reference for the clinical application of Astragalus and the future development of novel antioxidants.

Cinnamomum camphora seed kernel protein isolate (CPI) has attracted increasing attention due to its sustainability and potential applications. This study aimed to investigate the effects of freeze-drying (FD), vacuum-drying (VD), and spray-drying (SD) on the physicochemical and functional properties of CPI. The morphology observation results showed that the SD-CPI, SD-CPI, and VD-CPI were spherical, lamellar, and massive, respectively. Compared to FD and SD, VD had more impact on the color, surface hydrophobicity, intermolecular disulfide bonds, intrinsic fluorescence, and thermal stability of CPI. Fourier transform infrared spectroscopy (FTIR) analyses showed that among three CPI samples, VD-CPI had the highest content of β-sheet but the lowest contents of α-helix and β-turn. At different pH values, the solubility, emulsification, and foaming properties of VD-CPI were inferior to those of FD-CPI and SD-CPI. These results provide useful information on the changes in the physicochemical and functional properties of CPI subjected to different drying methods, and offer theoretical guidance for the production and use of CPI in the food industry.

Summary: Background: Cervical squamous cell carcinoma (CSCC) and adenocarcinoma (CAde) are two major pathological types of cervical cancer (CC), but their high-resolution heterogeneity of tumor and immune microenvironment remains elusive. Methods: Here, we performed single-nucleus RNA sequencing (snRNA-seq) from five CSCC and three CAde samples, and systematically outlined their specific transcriptome atlas. Findings: We found CD8+ T cells in CSCC were more cytotoxic but lower exhausted compared to those in CAde, and phagocytic MRC1+ macrophages were specifically enriched in CSCC. Interestingly, we discovered that pro-tumoral cancer-associated myofibroblasts (myoCAFs) and cancer-associated vascular-fibroblasts (vCAFs) were more abundant in CSCC, and further verified their pro-metastatic roles in vitro. Furthermore, we also identified some specific chemotherapy drugs for CSCC (Dasatinib and Doramapimod) and CAde (Pyrimethamine and Lapatinib) by revealing their heterogeneity in transcriptomic profiles of malignant epithelial cells, and further verified their specific sensitivity in cell lines and constructed CC-derived organoids. Cell–cell communication networks revealed that the pathways of NRG1-ERBB2, and FN1-ITAG3 were specific for CAde and CSCC, respectively, which may partly explain the specificities of identified chemotherapy drugs. Interpretation: Our study described the immune heterogeneity and specific cellular interactions between CSCC and CAde, which could provide insights for uncovering pathogenesis and designing personalized treatment. Fundings: National Key R&D Program of China (2021YFC2701201), National Natural Science Foundation of China (82072895, 82141106, 82103134, 81903114).

Background The present study aims to use structural equation modelling (SEM) with multiple regression pathways to examine direct and indirect links from diet and metabolic traits to microvascular endothelial dysfunction (ED) among middle-aged Chinese males.Methods The study was conducted in middle-aged Chinese males, who underwent a health check-up between 2018 and 2019. Data on lifestyle behaviour factors (physical activity, diet pattern, sleep quality and diet data underwent factor analysis in advance) and metabolic risk factors referring to metabolic traits were introduced into the SEM to examine inter-relationship among these factors and their association with ED, as evaluated by the reactive hyperaemia index (RHI).Results Both exploratory factor analysis and confirmatory factor analysis identified two major dietary patterns: ‘prudent pattern’ and ‘western pattern’. The univariate test suggested that only triglycerides (TGs) and prudent dietary pattern were directly associated with RHI. Furthermore, prudent dietary pattern had an indirect association with RHI via TG (prudent diet→TG: β=−0.15, p

Here the authors developed a nucleolus Hi-C technique (nHi-C) for enriching nucleolus-associated interactions, and revealed specific heterochromatin interaction patterns within and around nucleoli in human cells at high resolution.

Abstract Background Severe neonatal thrombocytopenia is a rare disease with multiple etiologies. Severe thrombocytopenia with bleeding is life-threatening and has attracted significant attention from clinicians. However, only a few studies have focused on the association between severe thrombocytopenia and bleeding. Thus, this study aimed to describe the neonates’ postnatal age at which severe thrombocytopenia was first recognized, clinical characteristics, bleeding patterns, and outcomes and to evaluate the association between minimum platelet count and bleeding. Methods A single-center retrospective cohort study for neonates with severe thrombocytopenia (platelet count ≤ 50 × 109/L) was conducted. Neonates who were admitted to our neonatal intensive care unit between October 2016 and February 2021 and developed severe thrombocytopenia were analyzed. Data were collected retrospectively until the patients were referred to other hospitals, discharged, or deceased. Results Among the 5819 neonatal inpatients, 170 with severe thrombocytopenia were included in this study. More than 30% of the patients had severe thrombocytopenia in the first 3 days of life. Among the 118 neonates with bleeding, 47 had more than one type of pathological bleeding. Neonates with very severe thrombocytopenia (point estimate: 53.7%, 95% confidence interval [CI]: 44.2%–63.1%) had a higher incidence rate of cutaneous bleeding than those with severe thrombocytopenia (point estimate: 23.4%, 95% CI: 12.3%–34.4%). The gestational age (median: 36.2 [interquartile range [IQR]: 31.4–39.0] weeks) and birth weight (median: 2310 [IQR: 1213–3210] g) of the major bleeding group were the lowest among no bleeding, minor bleeding, and major bleeding groups. Regression analysis controlled for confounders and confirmed that a lower platelet count (odds ratio [OR]: 2.504 [95% CI: 1.180–5.314], P = 0.017) was associated with a significant increase in the rate of bleeding. Very severe thrombocytopenia (point estimate: 49.1%, 95% CI: 39.6%–58.6%) had a higher rate of platelet transfusion than severe thrombocytopenia (point estimate: 5.7%, 95% CI: 0.7%–10.7%). The mortality rate was higher in neonates with bleeding than in those without bleeding (point estimates with 95% CI: 33.1% [24.4%–41.7%] vs. 7.7% [0.2%–15.2%]). Conclusions These findings describe the incidence of severe thrombocytopenia and demonstrate that a lower platelet count is associated with an increased bleeding rate in patients with severe thrombocytopenia.

Abstract Introduction Although aerobic physical exercise may improve osteoporosis during ageing, the underlying mechanism of the favorable effects remains unclear. The aim of this study was to examine the localized and generalized proinflammatory indicators and the adaptive skeletal responses to treadmill training in aged rats to explore the potential mechanisms by which treadmill training impacts bone deterioration in a natural aged rat model. Materials and methods A total of 24 Sprague Dawley (SD) rats were included in this study. Sixteen of all these animals were twenty-four months natural aged male SD rats, which were distributed into two groups (n = 8/group): AC group with sham treadmill training, and AT group with 8 weeks treadmill training. The remaining 8 were six months male SD rats matched subline and supplier, which were used as the adult control group with sham treadmill training (YC group, n = 8). The serum, bone marrow, fresh femur, tibia, and lumbar spine were harvested for molecular biological analysis, bone mineral density (BMD) testing, and micro-CT analysis after 8 weeks of treadmill training. Results After 8 weeks of intervention, the results showed that treadmill training increased BMD and inhibited deterioration of bone microarchitecture of hind limb bones. Further analysis showed that treadmill training increased serum P1CP concentration and decreased serum CTX-1level. Interestingly, treadmill training down-regulated the protein expressions of proinflammatory indicators, including NLRP3, proCaspase1, cleaved Caspase1, IL-1β, and GSDMD-N, and the mRNA levels of NLRP3, Caspase1, and IL-1β of the bone marrow. In addition, treadmill training also inhibited serum TNF-α and IL-1β concentration. However, 8 weeks of treadmill training did not increase BMD and bone microarchitecture in the lumbar spine. Conclusion Treadmill training mitigates the ageing-induced bone loss and reverses the deterioration of bone microarchitecture in hind limbs probably through inhibiting NLRP3/Caspase1/IL-1β signaling to attenuate low-grade inflammation and improve the inflammatory bone microenvironment.

Abstract Background Grain size and chalkiness is a critical agronomic trait affecting rice yield and quality. The application of transcriptomics to rice has widened the understanding of complex molecular responsive mechanisms, differential gene expression, and regulatory pathways under varying conditions. Similarly, metabolomics has also contributed drastically for rice trait improvements. As master regulators of plant growth and development, phys influence seed germination, vegetative growth, photoperiodic flowering, shade avoidance responses. OsPHYB can regulate a variety of plant growth and development processes, but little is known about the roles of rice gene OsPHYB in modulating grain development. Results In this study, rice phytochrome B (OsPHYB) was edited using CRISPR/Cas9 technology. We found that OsPHYB knockout increased rice grain size and chalkiness, and increased the contents of amylose, free fatty acids and soluble sugar, while the gel consistency and contents of proteins were reduced in mutant grains. Furthermore, OsPHYB is involved in the regulation of grain size and chalk formation by controlling cell division and complex starch grain morphology. Transcriptomic analysis revealed that loss of OsPHYB function affects multiple metabolic pathways, especially enhancement of glycolysis, fatty acid, oxidative phosphorylation, and antioxidant pathways, as well as differential expression of starch and phytohormone pathways. An analysis of grain metabolites showed an increase in the free fatty acids and lysophosphatidylcholine, whereas the amounts of sugars, alcohols, amino acids and derivatives, organic acids, phenolic acids, alkaloids, nucleotides and derivatives, and flavonoids decreased, which were significantly associated with grain size and chalk formation. Conclusions Our study reveals that, OsPHYB plays an important regulatory role in the growth and development of rice grains, especially grain size and chalkiness. Furthermore, OsPHYB regulates grain size and chalkiness formation by affecting gene metabolism interaction network. Thus, this study not only revealed that OsPHYB plays a vital role in regulating grain size and chalkiness of rice but reveal new functions and highlighted the importance and value of OsPHYB in rice grain development and provide a new strategy for yield and quality improvement in rice breeding.

A human induced pluripotent stem cell line (iPSC), FDCHi010-A, was derived from the peripheral blood of a 3-year-old patient with the c.2062C > T (p.R688*) mutation in the AHDC1 gene. The established cell line displayed a typical human embryonic stem cell-like morphology, exhibited a normal euploid karyotype, and fully expressed pluripotency markers. In addition, it retained the ability to differentiate to three germ layers. This cell line with a specific mutation may provide a useful tool for studying the pathogenesis and drug therapy screening of Xia-Gibbs syndrome caused by the AHDC1 gene.

Abstract Purpose To estimate the frequency of age-related macular degeneration (AMD) among people who underwent health examination in Hunan, China and to determine the relationship between dietary pattern and the risk of AMD. Methods The Questionnaire was used to collect dietary data from 56,775 study participants of ≥ 50 years old who underwent health examination at the Department of Health Management, the Third Xiangya Hospital of Central South University between January 2017 and December 2019. The diagnosis of AMD was based on the results of color fundus photography (CFP), spectral-domain optical coherence tomography (OCT) and multispectral imaging (MSI). After excluding participants with incomplete records or other ocular disease that may affect the results of fundus examination, a total of 43,672 study participants were included. The univariate and multivariate logistic regression analyses were used to determine the relationship between dietary pattern and the frequency of AMD. Results Among the 43,672 study participants, 1080 (2.5%) had early AMD: the frequencies were 2.6% (n = 674) in men and 2.3% (n = 406) in women; the frequencies were 1.0% (n = 289), 3.6% (n = 401), 9.1% (n = 390) in 50–59, 60–69, ≥ 70 years old, respectively. And the age-standard frequency was 6.6% over the 60 years old in Hunan China. The high-salt intake increased the risk of early AMD [odds ratio (OR) = 1.61, 95% confidence interval (CI) = 1.54–1.68], whereas the intake of meat decreased the risk (OR = 0.90, 95% CI = 0.81–0.99). Conclusion In Hunan China, there was a high frequency of early AMD detected through health examination over the 60 years old. And high-salt intake increases the risk of early AMD, whereas intake of meat decreases the risk. Modulating the dietary pattern and reducing the salt intake as an AMD prevention strategy warrant further study.

Abstract Background Evidence for the association of thyroid dysfunction and autoantibody positivity with preterm birth remains controversial. We aimed to study the association of maternal thyroid dysfunction and autoantibody positivity with the risk of preterm birth. Method A hospital-based cohort study of 40,214 women was conducted. Gestational age-specific percentiles of the FT4 and TSH concentrations were used for the definition of thyroid dysfunction. Autoantibody positivity was identified when the concentration > the threshold. The association of thyroid dysfunction and autoantibody positivity with the risk of preterm birth was estimated. Results No significant higher risk of preterm birth was found for women with variants of thyroid dysfunction or autoantibody positive than euthyroid women. Sensitivity and stratification analyses indicated that thyroperoxidase antibody (TPOAb) positivity in the first trimester (odds ratio [OR], 1.49; 95% confidence interval [CI], 1.17–1.90) and overt hypothyroidism restricted to women negative for TPOAb (OR, 4.94; 95%CI: 1.64–14.84) was associated with an increased risk of preterm birth. Modification effects of gestational age were found for women who had the test ≤18 and > 18 weeks. Continuous FT4 measurements tested ≤18 weeks of gestation were associated with a higher risk of preterm birth (OR, 1.13, 95% CI: 1.00–1.28), while a negative relationship for FT4 concentrations tested > 18 weeks of gestation (OR = 0.68, 95% CI: 0.48–0.97). Conclusions Some specific thyroid function abnormalities were associated with an increased risk of preterm birth. Interaction between gestational age and FT4 concentration on the risk of preterm birth was identified, with a critical node of 18 weeks of gestation.

Air pollution is of high relevance to human health. In this study, multiple machine-learning (ML) models—linear regression, random forest (RF), AdaBoost, and neural networks (NNs)—were used to explore the potential impacts of air-pollutant concentrations on the incidence of pediatric respiratory diseases in Taizhou, China. A number of explainable artificial intelligence (XAI) methods were further applied to analyze the model outputs and quantify the feature importance. Our results demonstrate that there are significant seasonal variations both in the numbers of pediatric respiratory outpatients and the concentrations of air pollutants. The concentrations of NO2, CO, and particulate matter (PM10 and PM2.5), as well as the numbers of outpatients, reach their peak values in the winter. This indicates that air pollution is a major factor in pediatric respiratory diseases. The results of the regression models show that ML methods can capture the trends and turning points of clinic visits, and the non-linear models were superior to the linear ones. Among them, the RF model served as the best-performing model. The analysis on the RF model by XAI found that AQI, O3, PM10, and the current month are the most important predictors affecting the numbers of pediatric respiratory outpatients. This shows that the number of outpatients rises with an increasing AQI, especially with the increasing of particulate matter. Our study indicates that ML models with XAI methods are promising for revealing the underlying impacts of air pollution on the pediatric respiratory diseases, which further assists the health-related decision-making.

Abstract Stem solidness is an important agronomic trait for increasing the ability of wheat to resist lodging. In this study, four new synthetic hexaploid wheat with solid stems were developed from natural chromosome doubling of F1 hybrids between a solid-stemmed durum wheat (Triticum turgidum ssp. durum, 2n = 4x = 28, AABB) and four Aegilops tauschii (2n = 2x = 14, DD) accessions. The solid expression of the second internode at the base of the stem was stable for two synthetic hexalpoid wheat Syn-SAU-117 and Syn-SAU-119 grown in both the greenhouse and field. The lodging resistance of four synthetic solid-stem wheats is stronger than that of CS, and Syn-SAU-116 has the strongest lodging resistance, followed by Syn-SAU-119. The paraffin sections of the second internode showed that four synthetic wheat lines had large outer diameters, well-developed mechanical tissues, large number of vascular bundles, and similar anatomical characteristics with solid-stemmed durum wheat. The chromosomal composition of four synthetic hexaploid wheat was identified by FISH (fluorescence in situ hybridization) using Oligo-pSc119.2-1 and Oligo-pTa535-1. At adult stage, all four synthetic hexaploid wheat showed high resistance to mixed physiological races of stripe rust pathogen (CYR31, CYR32, CYR33, CYR34). These synthetic hexaploid wheat lines provide new materials for the improvement of common wheat.

As a new computing paradigm, mobile edge computing (MEC) enables users to execute computation-intensive tasks at the network edge nodes (ENs) through computation offloading. Energy consumption of computation offloading is envisioned as a significant metric to satisfy the high quality of experience (QoE). In multi-ENs MEC networks, computation scheduling and power control of each user is tightly coupled with task offloading. Moreover, due to the stochastic task arrivals and unknown wireless channel conditions, it is challenging to allocate resources for efficient offloading without prior information of tasks and channels. In this paper, we propose an individualized utility metric of each user. We formulate the problem of computation scheduling and power control of each user as a stochastic optimization problem. We aim to maximize the long-term averaged utility quality of all users by jointly optimizing the computation scheduling, task-partition factor and power control. We use Lyapunov optimization technique to convert the long-term stochastic problem into a series of deterministic sub-problems in each time slot. We propose an online algorithm for utility quality maximization (OAUQM). The asymptotic optimality and queue stability of our algorithm are analyzed. Experimental simulations are conducted to evaluate the performance of the proposed algorithm against the benchmark offloading algorithms in terms of utility quality and energy consumption.

This paper proposes an operational strategy based on the theory of transaction utility, aiming to mitigate the negative impact of customers’ free-riding behaviour. This operational strategy is named the reference price mechanism (RPM), in which the retailer gives a reference price that may be different from the retail price, and the customer’s purchase decision is affected by the reference price. Based on the Hotelling model, we develop a duopoly game by considering the free-riding cost to systematically discuss the effectiveness of the RPM. The results show that the brick-and-mortar/online retailer can benefit from implementing the RPM separately, vice versa. If both retailers implement the RPM, only the retailer with the higher reference price can attain more profits. In addition, there is a threshold of the free-riding cost that can affect whether the retailers implement the RPM.

CHARGE syndrome (OMIM 214800) is an autosomal dominant disease with coloboma, heart defects, atresia of choanae and retardation of growth and/or development, etc. CHD7 mutation is the major known pathogenic cause in patients with CHARGE syndrome. A human iPSC line with a novel heterozygous mutation (CHD7 c.2939 T > C) was constructed from peripheral blood mononuclear cells of a patient with CHARGE syndrome. The iPSC line showed normal karyotype, highly expressed pluripotency markers, and had differentiation potential of three germ layers. This iPSC line provides a useful model to study the underlying mechanisms and drug screening of CHARGE syndrome.

ObjectiveTo understand the infection characteristics and risk factors for infection by analyzing multicenter clinical data of newly diagnosed multiple myeloma (NDMM) patients.MethodsThis study reviewed 564 NDMM patients from 2 large tertiary hospitals from January 2018 to December 2021, of whom 395 comprised the training set and 169 comprised the validation set. Thirty-eight variables from first admission records were collected, including patient demographic characteristics, clinical scores and characteristics, laboratory indicators, complications, and medication history, and key variables were screened using the Lasso method. Multiple machine learning algorithms were compared, and the best performing algorithm was used to build a machine learning prediction model. The model performance was evaluated using the AUC, accuracy, and Youden’s index. Finally, the SHAP package was used to assess two cases and demonstrate the application of the model.ResultsIn this study, 15 important key variables were selected, namely, age, ECOG, osteolytic disruption, VCD, neutrophils, lymphocytes, monocytes, hemoglobin, platelets, albumin, creatinine, lactate dehydrogenase, affected globulin, β2 microglobulin, and preventive medicine. The predictive performance of the XGBoost model was significantly better than that of the other models (AUROC: 0.8664), and it also performed well for the expected dataset (accuracy: 68.64%).ConclusionA machine learning algorithm was used to establish an infection prediction model for NDMM patients that was simple, convenient, validated, and performed well in reducing the incidence of infection and improving the prognosis of patients.

Background: Kidney renal clear cell carcinoma (KIRC) is the most common pathological subtype of renal cell cancer. APOBEC3 activity has been identified in a variety of human cancers. Although its involvement in cancer has been studied widely, its influence on the tumor immune microenvironment remains poorly understood. Therefore, this study aimed to focus on the effect of APOBEC3 on tumor immune microenvironment of KIRC. Methods: In this study, we comprehensively analyzed the expression and prognostic significance of the APOBEC3 family in pan-cancer using multiple databases. The functions of key APOBEC3 family members were further investigated in KIRC, with APOBEC3G determined to be a candidate biomarker for unfavorable prognosis. We subsequently explored the correlation of APOBEC3G with the tumor immune environment in KIRC by analyzing the Cancer Genome Atlas (TCGA) dataset, then validated the prognostic significance and PD-L1 correlation of APOBEC3G by using tissue microarrays which included 233 primary tumor samples from patients with renal clear cell carcinoma. Results: The APOBEC3 family was overexpressed in KIRC and high APOBEC3 expression predicted poor prognosis. In addition, APOBEC3G was positively correlated with the expression of immunoinhibitors such as TIGIT, LAG3, CD96, PD-1, and CTLA4. In addition, APOBEC3G had a positive correlation with immunosuppressive cells, including regulatory T cell and myeloid-derived suppressor cell. Finally, based on 233 clinical samples, we validated that high expression of APOBEC3G contributed to a poor prognosis for KIRC patients and the positive relationship between APOBEC3G and PD-L1 expression. High APOBEC3G expression was also found to be more common in patients with sarcomatoid histology (P = 0.0026). Conclusions: Our study showed that APOBEC3G was a prognostic biomarker correlated with the immune response in KIRC. In addition, APOBE3G had a positive correlation with PD-L1 expression and sarcomatoid histology, perhaps suggesting the potential impact of APOBEC3G on immunotherapy.

Abstract The effective treatment of advanced cervical cancer remains challenging. Herein, single‐nucleus RNA sequencing (snRNA‐seq) and SpaTial enhanced resolution omics‐sequencing (Stereo‐seq) are used to investigate the immunological microenvironment of cervical squamous cell carcinoma (CSCC). The expression levels of most immune suppressive genes in the tumor and inflammation areas of CSCC are not significantly higher than those in the non‐cancer samples, except for LGALS9 and IDO1. Stronger signals of CD56+ NK cells and immature dendritic cells are found in the hypermetabolic tumor areas, whereas more eosinophils, immature B cells, and Treg cells are found in the hypometabolic tumor areas. Moreover, a cluster of pro‐tumorigenic cancer‐associated myofibroblasts (myCAFs) are identified. The myCAFs may support the growth and metastasis of tumors by inhibiting lymphocyte infiltration and remodeling of the tumor extracellular matrix. Furthermore, these myCAFs are associated with poorer survival probability in patients with CSCC, predict resistance to immunotherapy, and might be present in a small fraction (< 30%) of patients with advanced cancer. Immunohistochemistry and multiplex immunofluorescence staining are conducted to validate the spatial distribution and potential function of myCAFs. Collectively, these findings enhance the understanding of the immunological microenvironment of CSCC and shed light on the treatment of advanced CSCC.

Ensemble prediction systems (EPSs) serve as a popular technique to provide probabilistic precipitation prediction in short- and medium-range forecasting. However, numerical models still suffer from imperfect configurations associated with data assimilation and physical parameterization, which can lead to systemic bias. Even state-of-the-art models often fail to provide high-quality precipitation forecasting, especially for extreme events. In this study, two deep-learning-based models—a shallow neural network (NN) and a deep NN with convolutional layers (CNN)—were used as alternative post-processing approaches to further improve the probabilistic forecasting of precipitation over China with 1–7 lead days. A popular conventional method—the censored and shifted gamma distribution-based ensemble model output statistics (CSG EMOS)—was used as the baseline. Re-forecasts run using a frozen EPS—Global Ensemble Forecast System version 12—were collected as the raw ensembles spanning from 2000 to 2019. The re-forecast data were generated once per day and consisted of one control run and four perturbed members. We used the calendar year 2018 as the validation period and 2019 as the testing period, and the remaining 18 years of data were used for training. According to the results, in terms of the continuous ranked probability score (CRPS) and the Brier score, the CNN model significantly outperforms the shallow NN model, as well as the CSG EMOS approach and the raw ensemble, especially for heavy or extreme precipitation events (those exceeding 50 mm/day). A remarkable degradation was seen when reducing the size of training samples from 18 years of data to two years. The spatial distribution of the CRPS shows that the stations in central China were better calibrated than those in other regions. With a lead time of 1 day, the CNN model was found to be superior to the other models (in terms of the CRPS) at 74.5% of the study stations. These results indicate that deep NNs can serve as a promising approach to the statistical post-processing of probabilistic precipitation forecasting.

PurposeAs a new human resource management practice, idiosyncratic deals are personalized employment arrangements negotiated between employees and employers and intended to benefit them both. It plays an important role in attracting, retaining and motivating employees to promote breakthrough innovation. Based on the input-process-output (I-P-O) model, this paper examines the relationship between team idiosyncratic deals and team breakthrough innovation, the mediating role of team exploratory-exploitative knowledge sharing, and the moderating roles of team transactive memory systems and team cognitive flexibility.Participants and methodsIn order to reduce the effects of common method biases and causal lag effect, this study is divided into three stages for data collection, with a time interval of 1 month. Eighty teams (406 employees) from six enterprises in Shanghai and Hangzhou were selected as samples, and the hypothesis test was carried out by hierarchical regression analysis, bootstrap, and Johnson-Neyman method.ResultsThe results show that higher team idiosyncratic deals are associated with higher team breakthrough innovation through higher team exploratory-exploitative knowledge sharing, and that team transactive memory systems and team cognitive flexibility positively moderate the mediating effect of team exploratory-exploitative knowledge sharing in the relationship between team idiosyncratic deals and team breakthrough innovation in the first stage and the second stage, respectively. Under the joint effect of high team transactive memory systems and high team cognitive flexibility, the mediating effect of team exploratory-exploitative knowledge sharing is stronger.ConclusionThe research results break through the previous research framework of social exchange theory, and I-P-O model to explore the influence mechanism of team idiosyncratic deals, in order to promote the sustainable growth of team breakthrough innovation through this non-standard work arrangement. It is hoped that this research can inspire modern enterprises to create team idiosyncratic deals for valuable teams engaged in breakthrough innovation, which are more conducive to give full play to their heterogeneous talents, and finally help enterprises break through the industry bottleneck and win the market competition.

Nitrogen is one of the important factors for high yield of rice. Apart from high yield, high quality has become the current urgent demand for rice production. Grain-filling stage is crucial for rice yield and quality formation. However, the effect of nitrogen on grain-filling characteristics and the relationship of grain-filling characteristics and rice quality of mid-season indica rice were still unclear. A field experiment was carried out to ascertain the critical grain-filling characteristics that contribute to rice milling quality, appearance quality and cooking and eating quality under nitrogen applications. The results showed that nitrogen applications prolonged the duration of superior and inferior grain filling. The mean grain-filling rate (Gmean) and the maximum grain-filling rate (Gmax) of the inferior grains were positively correlated with chalky kernel rate, chalkiness, and amylose content. The time reaching the maximum grain-filling rate (Tmax G) of the inferior grains was positively correlated with brown rice rate, milled rice rate, and head milled rice rate. Chalky kernel rate and chalkiness were negatively correlated with peak paste viscosity and breakdown viscosity. Less amylose content and more crude protein content were detected in nitrogen application of Liangyoupei 9 and Y Liangyou 2 both in 2016 and 2017. According to the correlation analysis, better cooking and eating quality of Y Liangyou 2 which had less amylose content might result from its higher Gmax and Gmean of inferior grain than that of Liangyoupei 9 in the treatments of nitrogen application. These results indicated that the prolonging grain-filling duration and increasing grain weight at the maximum grain-filling rate of inferior grains contributed to the improvement of milling quality, appearance quality, and cooking and eating quality of mid-season indica rice under appropriate nitrogen applications.

Abstract Graft‐versus‐host disease (GVHD) is a major life‐threatening complication of allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Inflammatory signaling pathways promote T‐cell activation and are involved in the pathogenesis of GVHD. Suppressor of cytokine signaling 1 (SOCS1) is a critical negative regulator for several inflammatory cytokines. However, its regulatory role in T‐cell activation and GVHD has not been elucidated. Multiomics analysis of the transcriptome and chromatin structure of granulocyte‐colony‐stimulating‐factor (G‐CSF)‐administered hyporesponsive T cells from healthy donors reveal that G‐CSF upregulates SOCS1 by reorganizing the chromatin structure around the SOCS1 locus. Parallel in vitro and in vivo analyses demonstrate that SOCS1 is critical for restraining T cell activation. Loss of Socs1 in T cells exacerbates GVHD pathogenesis and diminishes the protective role of G‐CSF in GVHD mouse models. Further analysis shows that SOCS1 inhibits T cell activation not only by inhibiting the colony‐stimulating‐factor 3 receptor (CSF3R)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, but also by restraining activation of the inflammasome signaling pathway. Moreover, high expression of SOCS1 in T cells from patients correlates with low acute GVHD occurrence after HSCT. Overall, these findings identify that SOCS1 is critical for inhibiting T cell activation and represents a potential target for the attenuation of GVHD.

Abstract Background A lack of information on specific and interventional factors for stillbirth has made designing preventive strategies difficult, and the stillbirth rate has declined more slowly than the neonatal death rate. We compared the prevalence of stillbirth among the offspring of women with or without abnormal placental perfusion (APP). Methods We conducted a hospital-based retrospective cohort study involving women with a singleton pregnancy between 2012 and 2016 (N = 41,632). Multivariate analysis was performed to compare the prevalence of stillbirth in infants exposed to APP (defined as any abnormality in right or left uterine artery pulsatility index or resistance index [UtA-PI, −RI] [e.g., > 95th percentile] or presence of early diastolic notching) with that in those not exposed to APP. Results Stillbirths were more common among women with APP than among those with normal placental perfusion (stillbirth rate, 4.3 ‰ vs 0.9 ‰; odds ratio (OR), 4.2; 95% confidence interval (CI), 2.2 to 8.0). The association strengths were consistent across groups of infants exposed to APP that separately defined by abnormality in right or left UtA-PI or -RI (OR ranged from 3.2 to 5.3; all P ≤ 0.008). The associations were slightly stronger for the unexplained stillbirths. Most of the unexplained stillbirth risk was attributed to APP (59.0%), while a foetal sex disparity existed (94.5% for males and 58.0% for females). Women with normal placental perfusion and a male foetus had higher credibility (e.g., higher specificities) in excluding stillbirths than those with APP and a female foetus at any given false negative rate from 1 to 10% (93.4% ~ 94.1% vs. 12.3% ~ 14.0%). Conclusions APP is associated with and accounts for most of the unexplained stillbirth risk. Different mechanisms exist between the sexes. The performance of screening for stillbirth may be improved by stratification according to sex and placental perfusion.

To explore the differences in hoarding strategies of rodents for different seeds in various seasons, we labeled and released the seeds of Pinus koraiensis, Corylus mandshurica, Quercus mongolica and Prunus sibirica in temperate forests of Northeast China and investigated the fate of the seeds in spring and autumn. The analysis showed that the hoarding strategies of the rodents varied substantially between seasons. The seeds were consumed faster in the spring than in the autumn. More than 50% of the seeds in the two seasons were consumed by the 16th day. It took 36 days to consume 75% of the seeds in the spring and 44 days in the autumn. The rate of consumption of the seeds in the spring was greater than in the autumn, and the rate of spread of the seeds was greater in the autumn. The distances of removal for the consumption and dispersal of seeds in the spring (3.26 ± 3.21 m and 4.15 ± 3.52 m, respectively) were both shorter than those in the autumn (3.74 ± 3.41 m and 4.87 ± 3.94 m, respectively). In addition, the fate of different seeds varied significantly owing to differences in hoarding strategies. The seeds of the three preferred species, P. koraiensis, C. mandshurica, and Q. mongolica, were quickly consumed. More than 90% of the seeds of these species were consumed. Only 21% of Pr. sibirica seeds were slowly consumed, and the two seasons had the same seed consumption rate patterns: the consumption rate of P. koraiensis seeds was the highest, followed by C. mandshurica, then Q. mongolica, and finally Pr. sibirica. The median removal times of the two seasons were different, but the rules were the same: P. koraiensis was the shortest, followed by C. mandshurica, and the third was Q. mongolica. In both seasons, the most predated in situ seeds were those of P. koraiensis; the most hoarded seeds were those of C. mandshurica, and the most unconsumed seeds were those of Pr. sibirica.

Soil microorganisms are greatly affected by their microenvironment. To reveal the influence of different land use patterns on the composition and diversity of soil bacterial and fungal communities, this study analyzed microbial (bacteria and fungi) community composition and diversity under different land use patterns (vegetable land, wasteland, woodland, cultivated land) based on 16S rRNA, 18S rRNA, and high-throughput sequencing method in the Taojia River Basin. Spearman analysis and redundancy analysis (RDA) were used to explore the correlation between soil physicochemical properties and soil fungal and bacterial community composition, and a partial least squares path model (PLS-PM) was constructed to express the causal relationship between soil physicochemical properties and soil bacterial and fungal community diversity. The results showed that the soil bacterial species richness was highest in vegetable land and the lowest in the wasteland. Proteobacteria is the dominant phylum (20.69%–32.70%), and Actinobacteria is the dominant class (7.99%–16.95%). The species richness of fungi in woodland was the highest, while was the lowest in cultivated land. The dominant phylum of fungi in vegetable land, woodland, and cultivated land is Mucoromycota, 29.39%, 41.36%, and 22.67%, respectively. Ascomycota (42.16%) is the dominant phylum in wasteland. Sordariomyetes of Ascomycota is the dominant class in wasteland and cultivated land. Mortierellomycetes and Glomeromycetes of Mucoromycota are the dominant class in vegetable land and woodland. The results of the Spearman analysis revealed that the dominant groups in the bacterial and fungal communities had significant correlations with soil pH, clay, and sand (p < 0.01). The RDA results showed that soil clay, pH, and moisture were the key environmental factors affecting the diversity of soil microbial communities. Fungal diversity is more affected by different land use patterns than bacteria. These results provided a theoretical basis for the changes in soil microbial community composition and diversity in river basins.

Scheduling is one of the key technologies used in unmanned aerial vehicle (UAV) swarms. Scheduling determines whether a task can be completed and when the task is complete. The distributed method is a fast way to realize swarm scheduling. It has no central node and UAVs can freely join or leave it, thus making it more robust and flexible. However, the two most representative methods, the Consensus-Based Bundle Algorithm (CBBA) and the Performance Impact (PI) algorithm, pursue the minimum cost impact of tasks, which have optimization limitations and are easily cause task conflicts. In this paper, a new concept called “task consideration” is proposed to quantify the impact of tasks on scheduling and the regression of the task itself, balancing the exploration of the UAV for the minimum-impact task and the regression of neighboring tasks to improve the optimization and convergence of scheduling. In addition, the conflict resolution rules are modified to fit the proposed method, and the exploration of tasks is increased by a new removal method to further improve the optimization. Finally, through extensive Monte Carlo experiments, compared with CBBA and PI, the proposed method is shown to perform better in terms of task allocation and total travel time, and with the increase in the number of average UAV tasks, the number of iterations is less and the convergence is faster.

Seed dormancy is a key factor used to determine seed germination in rice production. So far, only a few genes controlling seed dormancy have been reported, and the genetic mechanism of rice seed dormancy is still elusive. In this study, a population of 195 diverse re-sequenced accessions from 40 countries was evaluated for the seed germination rate (GR) without dormancy breaking (WDB) as a control and under dry heating (DH) and gibberellic acid (GA) treatments, as dormancy breaking agents to identify QTLs for seed dormancy. Phenotypic assessment revealed that these accessions had abundant variations in seed dormancy. GWAS using 1,120,223 high-quality single nucleotide polymorphisms (SNPs) and a mixed linear model (MLM) incorporating both principal components (PCs) and kinship (K) identified 30 QTLs on 10 chromosomes, accounting for 7.3–20.4% of the phenotypic variance in GR. Ten of the QTLs were located in the regions of previously reported QTLs, while the rest were novel ones. Thirteen high-confidence candidate genes were predicted for the four QTLs detected in two or three conditions (qGR4-4, qGR4-5, qGR8 and qGR11-4) and one QTL with a large effect (qGR3). These genes were highly expressed during seed development and were significantly regulated by various hormone treatments. This study provides new insights into the genetic and molecular basis of rice seed dormancy/germination. The accessions with moderate and strong dormancy and markers for the QTLs and candidate genes are useful for attaining a proper level of seed dormancy.

Objective: To characterize and compare the microbiome signature in the maternal, intrauterine, and fetal environments and the associated bacterial species in women who experienced preterm birth and term birth. Methods: A total of 140 women with singleton pregnancies were enrolled in this study. Among them, 31 experienced spontaneous preterm delivery (gestational age < 37 weeks), and 28 of them experienced vaginal delivery at term. Maternal peripheral blood, saliva, and vaginal discharge samples and fetal membrane, amniotic fluid, and cord blood samples were collected immediately after delivery under sterile conditions. DNA was isolated from the fetal membrane and umbilical cord blood samples, and the V3–V4 region of the bacterial 16S rRNA gene was sequenced. The sequence data were quality-filtered, chimera-checked, and organized into operational taxonomic units (OTUs) based on phylogeny. Principal coordinate analysis of beta diversity measures was used for visualization. The linear discriminant analysis effect size (LEfSe) algorithm and Wilcoxon test were used to differentiate the microbiomes found in the fetal membranes and cord blood in the cases of preterm birth. Results: OTU analysis based on the 16S rRNA gene showed similar microbiomes in the maternal peripheral blood, amniotic fluid, fetal membranes, and cord blood. However, the LEfSe algorithm revealed significantly different bacterial compositions in the fetal environment between the preterm and term groups, with some of the bacterial species originating from the maternal peripheral blood or saliva. Conclusions: The bacteria in the intrauterine and fetal environments may originate from other body sites through hematogenous transmission, and may cause the occurrence of preterm birth.

Nanomaterials have attracted attention as antibacterial agents and have several modes of action. Here, the authors report on 2D transition metal disulphide nanosheets with hole boosted electron donation/withdrawal for enhanced antibacterial and biofilm activity caused by electron damage.

CRISPR-Cas systems are prokaryotic adaptive immunity against invading phages and plasmids. Phages have evolved diverse protein inhibitors of CRISPR-Cas systems, called anti-CRISPR (Acr) proteins, to neutralize this CRISPR machinery. In response, bacteria have co-evolved Cas variants to escape phage’s anti-CRISPR strategies, called anti-anti-CRISPR systems. Here we explore the anti-CRISPR allosteric inhibition and anti-anti-CRISPR rescue mechanisms between Streptococcus thermophilus Cas9 (St1Cas9) and the anti-CRISPR protein AcrIIA6 at the atomic level, by generating mutants of key residues in St1Cas9. Extensive unbiased molecular dynamics simulations show that the functional motions of St1Cas9 in the presence of AcrIIA6 differ substantially from those of St1Cas9 alone. AcrIIA6 binding triggers a shift of St1Cas9 conformational ensemble towards a less catalytically competent state; this state significantly compromises protospacer adjacent motif (PAM) recognition and nuclease activity by altering interdependently conformational dynamics and allosteric signals among nuclease domains, PAM-interacting (PI) regions, and AcrIIA6 binding motifs. Via in vitro DNA cleavage assays, we further elucidate the rescue mechanism of efficiently escaping AcrIIA6 inhibition harboring St1Cas9 triple mutations (G993K/K1008M/K1010E) in the PI domain and identify the evolutionary landscape of such mutational escape within species. Our results provide mechanistic insights into Acr proteins as natural brakes for the CRISPR-Cas systems and a promising potential for the design of allosteric Acr peptidomimetics.

International trade of goods is also flows of CO2. As a key exporter of harvested wood products (HWPs), China emits a large amount of CO2 to meet the consumption of other countries. This article uses an MRIO model to quantify the embodied CO2 emissions of China’s HWP sectors in international trade based on the WIOD database. China’s CO2 emissions from a production perspective were 121.25 Mt, more than four times those from a consumption perspective. China was a net exporter for embodied CO2 in HWP sectors, while the US was China’s largest importer. In addition, the furniture sector exported more embodied CO2 by international trade than those from the wood and paper sectors. Based on the unbalances of exports and imports, establishing a common international standard to share the responsibility for CO2 emissions is of great urgency in HWP sectors. This article facilitates promoting CO2 emission reduction in HWP sectors and references China’s future participation in international trade and environmental negotiations.