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Abstract There remains a critical need for the precise control of CRISPR (clustered regularly interspaced short palindromic repeats)-based technologies. Here, we engineer a set of inducible CRISPR-based tools controllable by focused ultrasound (FUS), which can penetrate deep and induce localized hyperthermia for transgene activation. We demonstrate the capabilities of FUS-inducible CRISPR, CRISPR activation (CRISPRa), and CRISPR epigenetic editor (CRISPRee) in modulating the genome and epigenome. We show that FUS-CRISPR-mediated telomere disruption primes solid tumours for chimeric antigen receptor (CAR)-T cell therapy. We further deliver FUS-CRISPR in vivo using adeno-associated viruses (AAVs), followed by FUS-induced telomere disruption and the expression of a clinically validated antigen in a subpopulation of tumour cells, functioning as “training centers” to activate synthetic Notch (synNotch) CAR-T cells to produce CARs against a universal tumour antigen to exterminate neighboring tumour cells. The FUS-CRISPR(a/ee) toolbox hence allows the noninvasive and spatiotemporal control of genomic/epigenomic reprogramming for cancer treatment.

ABSTRACTThe decline in air quality is thought to be due to rapid land use/land cover (LULC) changes near metropolitan areas that are undergoing rapid urbanisation. Here, we quantify the characteristics and relationship between the aerosol optical depth (AOD) index and LULC changes in Hangzhou, China, since the 21st century using multispectral satellite remote sensing data. The regional study results show that the correlation between the operational AOD observations (MOD04_3K) at 3 km resolution and the in situ AOD measurements available in Hangzhou ranges from 0.48 to 0.80, and their root mean square error (RMSE) < 0.30. During the past two decades, Hangzhou has been in the stage of rapid urbanisation, and the area of construction land has increased significantly, mainly converted from cultivated land and forests. The correlation coefficients between the AOD and the changes of cultivated land, forest land, grassland and construction land in Hangzhou were 0.36, 0.86, 0.61 and 0.63, respectively, indicating a strong correlation except for the cultivated land. Finally, the temporal evolution of the correlation coefficients between the cultivated land and building land are positively correlated with AOD, while from the trend of the correlation curve, grassland, woodland and AOD show negative correlations.

In terrestrial ecosystems, carbon (C) transportation and C pool transformation processes both occur at the land-river-estuary continuum. Moreover, C budget and C balance processes are generally critical in achieving the C neutrality of terrestrial ecosystems. This study analyzes key C transportation processes at multiple interfaces that collectively constitute the land-river-estuary continuum, discusses C transportation and sedimentation processes at the land-river interface, and reveals aquatic plant C sequestration coupling processes and associated productivity. Transformation mechanisms of inorganic-organic C pools are also investigated here as well as a systematic evaluation of C transport flux within the different interfaces that constitute the land-river-estuary continuum. Results show that the net C sink of terrestrial ecosystems was 1.70 Pg C yr−1, wherein the gross primary productivity (GPP) of global terrestrial vegetation reached 123 Pg C yr−1, while rock weathering also consumed 0.30 Pg C yr−1 of atmospheric carbon dioxide (CO2). Subsequently, the C transported by the land-river-estuary continuum reached 1.70 Pg C yr−1. During this process, 0.20 Pg C is deposited and buried in inland water and 1.00 Pg C escapes from inland water systems each year. Therefore, only 0.85 Pg C is transported to the estuary. Finally, this study clarifies control mechanisms of C transportation and transformation processes at the land-river-estuary continuum. The aim of this study is to provide an important scientific basis for the quantitative analysis of C sources and sinks at the land-river-estuary continuum and C neutrality of the biosphere.

Accurate volumetric error model is the basis for accuracy design. In this paper, a universal model for volumetric error prediction considering tolerance is proposed. Firstly, geometric error parameters are obtained by analysing the motion forms of key components. Secondly, the map between geometric error and tolerance is developed using Fourier function. Subsequently, the volumetric error prediction model (VEPM) is established based on key component tolerance. The model was applied to guide the development of machine tools. Finally, model validation experiments are carried out with two configurations of machine tools. The results show that, for the horizontal grinder, the predicted values for ±45° diagonal errors are 0–2.7 μm and 0–4.5 μm, which are consistent with the measured average values of 0.03–2.33 μm and −0.10–5.46 μm, respectively. Moreover, the predicted and measured values for +45° diagonal error of the vertical grinder are −15.0–0 μm and −15.07–0 μm, respectively. The experimental results illustrate the VEPM is effective and universal. The model has the potential to be applied to the design and development of machine tools.

Abstract Introduction Physical activity (PA) is believed to play an important part in many aspects during childhood and adolescence, especially cardiorespiratory fitness and cardiometabolic health. However, whether different levels of PA in daily life influence the structure or function of heart in school-aged children remains unknown. We aimed to investigate the association between PA and cardiovascular parameters in 7-year-old children. Methods Follow-up data from the Shanghai Prenatal Cohort Study and the Shanghai Birth Cohort was analyzed. Perinatal information including both maternal and offspring datum was recorded. A refined questionnaire was used to evaluate the frequency and duration of children’s PA levels. Blood pressure, echocardiography, and anthropometry assessment were conducted during the follow-up of 7-year-old children. Results Overall, high PA level was associated with higher left ventricle posterior wall thickness in diastole (LVPWd, β coefficient: 0.36, 95% CI: 0.12, 0.61), higher left ventricle mass index (LVMI, β = 0.28, 95% CI: 0.07, 0.48), mitral E/a ratio (β = 0.47, 95% CI: 0.22, 0.71) and slower heart rate (β = -0.32, 95% CI: -0.57, -0.07), compared to low PA level. Medium PA level was associated with lower diastolic blood pressure (DBP, β = -0.18, 95% CI: -0.35, -0.01). In subgroup analysis, increased relative wall thickness (RWT) was found in high PA level boys (β = 0.36, 95% CI: 0.05, 0.67), and systolic blood pressure (SBP) showed a significant decrease in high PA level girls (β = -0.42, 95% CI: -0.78, -0.06). Conclusions This study suggested non-athlete children having higher PA level were associated with thicker left ventricle (LV) walls and better LV diastolic function, as well as slower heart rate and DBP at the age of 7. Furthermore, disparity in the association between PA level with morphological heart patterns and blood pressure existed in different sex category.

Abstract Background It is not fully established whether plasma β-amyloid(Aβ)42/Aβ40 and phosphorylated Tau181 (p-Tau181) can effectively detect Alzheimer’s disease (AD) pathophysiology in older Chinese adults and how these biomarkers correlate with astrocyte reactivity, Aβ plaque deposition, tau tangle aggregation, and neurodegeneration. Methods We recruited 470 older adults and analyzed plasma Aβ42/Aβ40, p-Tau181, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) using the Simoa platform. Among them, 301, 195, and 70 underwent magnetic resonance imaging, Aβ and tau positron emission tomography imaging. The plasma Aβ42/Aβ40 and p-Tau181 thresholds were defined as ≤0.0609 and ≥2.418 based on the receiver operating characteristic curve analysis using the Youden index by comparing Aβ-PET negative cognitively unimpaired individuals and Aβ-PET positive cognitively impaired patients. To evaluate the feasibility of using plasma Aβ42/Aβ40 (A) and p-Tau181 (T) to detect AD and understand how astrocyte reactivity affects this process, we compared plasma GFAP, Aβ plaque, tau tangle, plasma NfL, hippocampal volume, and temporal-metaROI cortical thickness between different plasma A/T profiles and explored their relations with each other using general linear models, including age, sex, APOE-ε4, and diagnosis as covariates. Results Plasma A+/T + individuals showed the highest levels of astrocyte reactivity, Aβ plaque, tau tangle, and axonal degeneration, and the lowest hippocampal volume and temporal-metaROI cortical thickness. Lower plasma Aβ42/Aβ40 and higher plasma p-Tau181 were independently and synergistically correlated with higher plasma GFAP and Aβ plaque. Elevated plasma p-Tau181 and GFAP concentrations were directly and interactively associated with more tau tangle formation. Regarding neurodegeneration, higher plasma p-Tau181 and GFAP concentrations strongly correlated with more axonal degeneration, as measured by plasma NfL, and lower plasma Aβ42/Aβ40 and higher plasma p-Tau181 were related to greater hippocampal atrophy. Higher plasma GFAP levels were associated with thinner cortical thickness and significantly interacted with lower plasma Aβ42/Aβ40 and higher plasma p-Tau181 in predicting more temporal-metaROI cortical thinning. Voxel-wise imaging analysis confirmed these findings. Discussion This study provides a valuable reference for using plasma biomarkers to detect AD in the Chinese community population and offers novel insights into how astrocyte reactivity contributes to AD progression, highlighting the importance of targeting reactive astrogliosis to prevent AD.

ABSTRACT The endophyte is closely related to medicinal plant growth and development, stress resistance, and active ingredients’ accumulation. However, a seasonal succession of endophytes and the association with active ingredients is still unclear. In this study, we used high-throughput sequencing methods to compare the endophyte diversity of Rheum palmatum under different seasons and analyze the association between endophytes and five active ingredients. The results show that the diversity of endophytic fungi increased and then decreased, while bacterial diversity increased with the change of season. Community composition showed that the dominant genera of endophytic fungi were different under the different seasons, while the dominant genera of endophytic bacteria were Delftia. Analysis of co-occurrence network maps showed that the connectivity and complexity of endophytic fungi and bacterial networks decreased with the change of season. Spearman analysis indicated that the active ingredients of R. palmatum were significantly positive correlation with genera of endophytic fungi (Chalara). FUNGuild and PICRUSt predictive analysis indicated that the function of endophytic fungi and bacteria, respectively, were symbiotroph and metabolism, and relative abundances were different under the different seasons. Our results help elucidate the mechanism of medicinal plant–endophyte interaction.IMPORTANCEThrough the investigation of the seasonal succession of endophytes and the association with active ingredients in Rheum palmatum, we found that the diversity and composition of endophytes in R. palmatum exhibited seasonal dynamics, and the active ingredients of R. palmatum showed a significantly positive correlation with the genus of endophytic fungi (Chalara). Our results may lay a foundation for understanding the interaction mechanism of endophyte and medicinal plant, and can also provide a theoretical basis for sustainable production of medicinal plants.

ABSTRACT Females and males of dioecious plants have evolved sex-specific characteristics in terms of their morphological and physiological properties. However, little is known about the difference in rhizosphere microbes in dioecious plants. In this study, we used amplicon sequencing to analyze the differences in rhizosphere microbial diversity and community composition of males and females of dioecious Hippophae tibetana at different habitats, and their key factors in driving the differences were investigated. The results showed that there were differences in the diversity, community composition, and connectivity and complexity of the co-occurrence network of rhizosphere microbes between females and males of the dioecious H. tibetana at different habitats. Zoopagomycota is a unique phylum of rhizosphere fungi in the males of the dioecious H. tibetana, while Dependentiae is a unique phylum of rhizosphere bacteria in the females of the dioecious H. tibetana. Linear discriminant analysis effect size (LEfSe) analysis indicated significant enrichment of species at different levels, suggesting that these species could be potential biomarkers for females and males of H. tibetana. Spearman’s analysis showed that the dominant genera of rhizosphere fungi were significantly positively correlated with soil physicochemical properties (total nitrogen and phosphorus; organic matter; available phosphorus, potassium and nitrogen; salt content; water content). PICRUSt and FUNGuild predictive analysis indicated that the function of rhizosphere fungi was different between females and males of the dioecious H. tibetana at different habitats, while metabolites were the dominant functions of rhizosphere bacteria in all samples. These results highlighted the sexual discrimination of rhizosphere microbes on the dioecious plants and provided important knowledge for females and males of the dioecious plant–microbe interaction.IMPORTANCEThis study explores the differences in rhizosphere microbes of dioecious Hippophae tibetana at different habitats and their key factors in driving the differences. Through employing amplicon sequencing techniques, we found that rhizosphere microbial communities and diversity were different between females and males of the dioecious H. tibetana at different habitats, and there notably existed unique phylum and potential biomarkers of rhizosphere microbes between females and males of the dioecious H. tibetana. Rhizosphere fungi were significantly positively correlated with soil physicochemical properties. This study reveals the differences in rhizosphere microbes of dioecious H. tibetana at different habitats and driving factors; it also contributes to our understanding of the dioecious plant–microbe interaction.

Abstract. Background:. Intrauterine valvuloplasty is an innovative therapy, which promotes ventricular growth and function in some congenital heart diseases (CHDs). The technique remains challenging and can only be performed in a few centers. This study aimed to assess the feasibility and mid-term outcomes of fetal cardiac intervention (FCI) in fetuses with critical CHD in an experienced tertiary center. Methods:. Five fetal aortic valvuloplasty (FAV) or fetal pulmonary valvuloplasty (FPV) procedures were performed in our fetal heart center between August 2018 and May 2022. Technical success was defined as crossing the aortic or pulmonary valve and balloon inflation, followed by evidence of increased blood flow across the valve and/or new regurgitation. Follow-up clinical records and echocardiography were obtained during the prenatal and postnatal periods. Results:. Five fetuses received FAV or FPV, including critical aortic stenosis ( n = 2) and pulmonary atresia with intact ventricular septum ( n = 3). The mean maternal age was 33.0 ± 2.6 years. The median gestational age (GA) at diagnosis was 24 weeks (range, 22–26 weeks). The median GA at intervention was 29 weeks (range, 28–32 weeks). All five cases underwent successful or partially successful procedures. One patient had pulmonary valve perforation without balloon dilation. No procedure-related deaths or significant complications occurred. However, one neonatal death occurred due to heart and renal failure. The median follow-up period was 29.5 months (range, 8.0–48.0 months). The four surviving patients had achieved biventricular circulation, exhibited improved valve, and ventricular development at the last follow-up visit. Conclusion:. Intrauterine FCI could be performed safely with good prognosis in critical CHD.

Abstract In the present study, a new turbomolecular pump (TMP) performance prediction algorithm is proposed according to the variable surface combined blade row (VSCBR) geometric model. The simulation calculation program is designed to perform structural optimization and flow field analysis. Research on the pumping performance of the traditional straight blade row (TSBR) indicates that when the blade velocity ratio is greater than 1, the increase in the pumping speed and compression ratio of the TMP gradually tends to stabilize. Response surface methodology is used to optimize the structural parameters of the first four stages of the combined blade row. The optimized VSCBR increases the pumping speed by 18.2% compared to that of the TSBR. The flow field analysis based on the optimized VSCBR shows that gas molecules reaching the rear blades are likely to approach the outlet, and the proportion of gas molecules in this region exceeds 50%. Therefore, the blades we designed should be conducive to additional gas molecules reaching the outlet.

Abstract The three-dimensional (3D) organization of genome is fundamental to cell biology. To explore 3D genome, emerging high-throughput approaches have produced billions of sequencing reads, which is challenging and time-consuming to analyze. Here we present Microcket, a package for mapping and extracting interacting pairs from 3D genomics data, including Hi-C, Micro-C, and derivant protocols. Microcket utilizes a unique read-stitch strategy that takes advantage of the long read cycles in modern DNA sequencers; benchmark evaluations reveal that Microcket runs much faster than the current tools along with improved mapping efficiency, and thus shows high potential in accelerating and enhancing the biological investigations into 3D genome. Microcket is freely available at https://github.com/hellosunking/Microcket .

Abstract In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients. Here, through in-depth integration of tumor transcriptome and patients’ prognoses across cancers, we investigated dysregulated and prognosis-associated genes and catalogued such important genes in a cancer type-dependent manner. Utilizing the expression matrices of these genes, we built models to quantitatively evaluate the malignant levels of tumors across cancers, which could add value to the clinical staging system for improved prediction of patients’ survival. Furthermore, we performed a transcriptome-based molecular subtyping on hepatocellular carcinoma, which revealed three subtypes with significantly diversified clinical outcomes, mutation landscapes, immune microenvironment, and dysregulated pathways. As tumor transcriptome was commonly profiled in clinical practice with low experimental complexity and cost, this work proposed easy-to-perform approaches for practical clinical promotion towards better healthcare and precision oncology of cancer patients.

Abstract Background Implicit absenteeism is very common among nurses. Poor perceived social support of intensive care unit nurses has a negative impact on their mental and physical health. There is evidence that lack of occupational coping self-efficacy can promote implicit absenteeism; however, the relationship between lack of occupational coping self-efficacy in perceived social support and implicit absenteeism of intensive care unit nurses is unclear. Therefore, this study aimed to evaluate the role of perceived social support between lack of occupational coping self-efficacy and implicit absenteeism of intensive care unit nurses, and to provide reliable evidence to the management of clinical nurses. Methods A cross-sectional study of 517 intensive care unit nurses in 10 tertiary hospitals in Sichuan province, China was conducted, of which 474 were valid questionnaires with a valid recovery rate of 91.6%. The survey tools included the Chinese version of Implicit Absenteeism Scale, the Chinese version of Perceived Social Support Scale, the Chinese version of Occupational Coping Self-Efficacy Scale and the Sociodemographic characteristics. Descriptive analysis and Pearson correlation analysis were performed using SPSS version 22.0, while the mediating effects were performed using AMOS version 24.0. Results The average of intensive care unit nurses had a total implicit absenteeism score of (16.87 ± 3.98), in this study, the median of intensive care unit nurses’ implicit absenteeism score was 17, there were 210 intensive care unit nurses with low implicit absenteeism (44.3%) and 264 ICU nurses with high implicit absenteeism (55.7%). A total perceived social support score of (62.87 ± 11.61), and a total lack of occupational coping self-efficacy score of (22.78 ± 5.98). The results of Pearson correlation analysis showed that implicit absenteeism was negatively correlated with perceived social support (r = -0.260, P

Abstract Angiogenesis is extensively involved in embryonic development and requires complex regulation networks, whose defects can cause a variety of vascular abnormalities. Cis-regulatory elements control gene expression at all developmental stages, but they have not been studied or profiled in angiogenesis yet. In this study, we exploited public DNase-seq and RNA-seq datasets from a VEGFA-stimulated in vitro angiogenic model, and carried out an integrated analysis of the transcriptome and chromatin accessibility across the entire process. Totally, we generated a bank of 47,125 angiogenic cis-regulatory elements with promoter (marker by H3K4me3) and/or enhancer (marker by H3K27ac) activities. Motif enrichment analysis revealed that these angiogenic cis-regulatory elements interacted preferentially with ETS family TFs. With this tool, we performed an association study using our WES data of TAPVC and identified rs199530718 as a cis-regulatory SNP associated with disease risk. Altogether, this study generated a genome-wide bank of angiogenic cis-regulatory elements and illustrated its utility in identifying novel cis-regulatory SNPs for TAPVC, expanding new horizons of angiogenesis as well as vascular abnormality genetics.

Abstract Introduction The Guangdong-Hong Kong-Macao Greater-Bay-Area of South China has an 86 million population and faces a significant challenge of Alzheimer’s disease (AD). However, the characteristics and prevalence of AD in this area are still unclear due to the rarely available community-based neuroimaging AD cohort. Methods Following the standard protocols of the Alzheimer’s Disease Neuroimaging Initiative, the Greater-Bay-Area Healthy Aging Brain Study (GHABS) was initiated in 2021. GHABS participants completed clinical assessments, plasma biomarkers, genotyping, magnetic resonance imaging (MRI), β-amyloid (Aβ) positron emission tomography (PET) imaging, and tau PET imaging. The GHABS cohort focuses on pathophysiology characterization and early AD detection in the Guangdong-Hong Kong-Macao Greater Bay Area. In this study, we analyzed plasma Aβ42/Aβ40 (A), p-Tau181 (T), neurofilament light, and GFAP by Simoa in 470 Chinese older adults, and 301, 195, and 70 had MRI, Aβ PET, and tau PET, respectively. Plasma biomarkers, Aβ PET, tau PET, hippocampal volume, and temporal-metaROI cortical thickness were compared between normal control (NC), subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia groups, controlling for age, sex, and APOE-ε4. The prevalence of plasma A/T profiles and Aβ PET positivity were also determined in different diagnostic groups. Results The aims, study design, data collection, and potential applications of GHABS are summarized. SCD individuals had significantly higher plasma p-Tau181 and plasma GFAP than the NC individuals. MCI and dementia patients showed more abnormal changes in all the plasma and neuroimaging biomarkers than NC and SCD individuals. The frequencies of plasma A+/T+ (NC; 5.9%, SCD: 8.2%, MCI: 25.3%, dementia: 64.9%) and Aβ PET positivity (NC: 25.6%, SCD: 22.5%, MCI: 47.7%, dementia: 89.3%) were reported. Discussion The GHABS cohort may provide helpful guidance toward designing standard AD community cohorts in South China. This study, for the first time, reported the pathophysiology characterization of plasma biomarkers, Aβ PET, tau PET, hippocampal atrophy, and AD-signature cortical thinning, as well as the prevalence of Aβ PET positivity in the Guangdong-Hong Kong-Macao Greater Bay Area of China. These findings provide novel insights into understanding the characteristics of abnormal AD pathological changes in South China’s older population.

The evasion of carbon dioxide (CO2) from lakes significantly influences the global carbon equilibrium. Amidst global climatic transformations, the role of Qingzang Plateau (QZP) lakes as carbon (C) sources or sinks remains a subject of debate. Furthermore, accurately quantifying their contribution to the global carbon budget presents a formidable challenge. Here, spanning half a century (1970–2020), we utilize a synthesis of literature and empirical field data to assess the CO2 exchange flux of QZP lakes. We find markedly higher CO2 exchange flux in the southeast lakes than that in the northern and western regions from 1970 to 2000. During this time, both freshwater and saltwater lakes served primarily as carbon sources. The annual CO2 exchange flux was estimated at 2.04 ± 0.37 Tg (Tg) C yr−1, mainly influenced by temperature fluctuations. The CO2 exchange flux patterns underwent a geographical inversion between 2000 and 2020, with increased levels in the west and decreased levels in the east. Notably, CO2 emissions from freshwater lakes diminished, and certain saltwater lakes in the QTP transitioned from carbon sources to sinks. From 2000 to 2020, the annual CO2 exchange flux from QZP lakes is estimated at 1.34 ± 0.50 Tg C yr−1, with solar radiation playing a more pronounced role in carbon emissions. Cumulatively, over the past five decades, QZP lakes have generally functioned as carbon sources. Nevertheless, the total annual CO2 emissions have declined since the year 2000, indicating a potential shift trend from being a carbon source to a sink, mirroring broader patterns of global climate change. These findings not only augment our understanding of the carbon cycle in plateau aquatic systems but also provide crucial data for refining China's carbon budget.

Abstract Plant growth promoting microbe assisted phytoremediation is considered a more effective approach to rehabilitation than the single use of plants, but underlying mechanism is still unclear. In this study, we combined transcriptomic and physiological methods to explore the mechanism of plant growth promoting microbe Trichoderma citrinoviride HT-1 assisted phytoremediation of Cd contaminated water by Phragmites australis. The results show that the strain HT-1 significantly promoted P. australis growth, increased the photosynthetic rate, enhanced antioxidant enzyme activities. The chlorophyll content and the activity of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) were increased by 83.78%, 23.17%, 47.60%, 97.14% and 12.23% on average, and decreased the content of malondialdehyde (MDA) by 31.10%. At the same time, strain HT-1 improved the absorption and transport of Cd in P. australis, and the removal rate of Cd was increased by 7.56% on average. Transcriptome analysis showed that strain HT-1 induced significant up-regulated the expression of genes related to oxidative phosphorylation and ribosome pathways, and these upregulated genes promoted P. australis remediation efficiency and resistance to Cd stress. Our results provide a mechanistic understanding of plant growth promoting microbe assisted phytoremediation under Cd stress.

Abstract Background New “noncardiac” problems in children with congenital heart disease (CHD), such as developmental delay or long-term neurodevelopmental impairments, have attracted considerable attention in recent years. It is hypothesized that exercise might attenuate CHD-associated neurodevelopmental impairments; however, this has not been thoroughly investigated. The objective of this prospective, single-blinded, randomized controlled experiment was to evaluate the impact of customized home-based exercise for children with CHD. Methods Children aged 0–5 years with echocardiography-confirmed simple CHD subtypes who were scheduled to undergo cardiac catheterization were screened for enrolment. Among 420 screened CHD children, 192 were enrolled and randomly assigned at a 1:1 ratio to receive a 6-month intervention (30 min daily customized home-based exercise program with supervision for no less than 5 days per week, combined with home-based exercise education) or control treatment (home-based education). The primary outcome was motor development (gross motor quotient (GMQ), fine motor quotient (FMQ), and total motor quotient (TMQ)). The secondary outcomes were cardiac function and structure, bone quality, physical development, parental anxiety, caregiver burden, and quality of life. Children and their families were assessed before and 1, 3, and 6 months after catheterization; 183 (95.3%) children were included in the primary analysis. Results After 6-month treatment, the intervention group significantly increased their motor quotient, which was consistently higher than that of the control group (GMQ p 0.017). For parents, higher quality of life level (total score p = 0.016) was observed in the intervention group; while effects of exercise on the anxiety (rude score p = 0.159, standard score p = 0.159) or the Zarit caregiver burden scale score (p = 0.404) were non-significant. No adverse events occurred during the study period. Conclusions Customized home-based exercise improved motor development in children with CHD. While the long-term effects of parent training in home-based exercise are unknown, the study results suggest positive outcomes. Trial registration A home-based exercise program in congenital heart disease children with cardiac catheterization: a randomized controlled trial. ( http://www.chictr.org.cn/ , ChiCTR-IOR-16007762, January 14, 2016).

In response to the issue of reduced horizontal bearing capacity due to inadequate compaction of backfill soil in traditional grillage foundations, a novel grillage root foundation is proposed in this study. That is, the root is introduced into undisturbed soil at a traditional grillage foundation base plate. To assess the applicability of this innovative foundation under horizontal loading conditions, on-site experimental research was conducted. It was employed to comparatively analyze the load–displacement curves, changes in internal forces of steel components, and the development patterns of soil cracks around the foundation between traditional grillage foundations and various sizes of grillage root foundations subjected to horizontal loading. The results indicate that the horizontal bearing capacity of the grillage root foundation increased by 1.3 times compared to traditional grillage foundations, with economic benefits surpassing those of the traditional counterparts. The determination of the “m” value serves as the proportional coefficient of the horizontal resistance coefficient of the foundation soil, and the synthesis of the reactive force provided by the soil to the roots contribute to enhancements in soil resistance and the horizontal bearing capacity of the foundation. The horizontal load at which cracks appear in the grillage root foundation exceeds that of the traditional metal grillage foundation, with a slower rate of development. Finite element analysis was conducted to optimize the arrangement of roots, maximizing the foundation’s bearing capacity. This research provides certain references in terms of enhancing foundation bearing capacity, reducing ground treatment costs, and promoting sustainable development.

At present, in the process of weld induction heat treatment, the common method is to carry out centralized induction heating in the weld area, which will lead to large radial temperature difference of the weld, poor controllability of temperature distribution and easy to cause the defects of residual stress concentration in the weld area. To solve the above problems, this paper adopts the two-sided method to conduct induction heating on both sides of the weld, and at the same time, the auxiliary pulse current is passed into the weld to improve the quality of the weld. ANSYS finite element software is used to establish a multi-field coupling prediction model of electric-magnetic-thermal structure, and explore the distribution law of the auxiliary pulse current and the temperature field of the weld. Finally, an experimental study of pulsed current assisted two-sided induction heating is carried out. Temperature test and metallographic test were carried out respectively to verify the effectiveness of pulsed current assisted induction heating technology.

Sea buckthorn (Hippophae rhamnoides ssp. sinensis) is a deciduous shrub or small tree in the Elaeagnaceae family. It is dioecious, featuring distinct structures in female and male flowers. The MADS-box gene family plays a crucial role in flower development and differentiation of floral organs in plants. However, systematic information on the MADS-box family in sea buckthorn is currently lacking. This study presents a genome-wide survey and expression profile of the MADS-box family of sea buckthorn. We identified 92 MADS-box genes in the H. rhamnoides ssp. Sinensis genome. These genes are distributed across 12 chromosomes and classified into Type I (42 genes) and Type II (50 genes). Based on the FPKM values in the transcriptome data, the expression profiles of HrMADS genes in male and female flowers of sea buckthorn showed that most Type II genes had higher expression levels than Type I genes. This suggesting that Type II HrMADS may play a more significant role in sea buckthorn flower development. Using the phylogenetic relationship between sea buckthorn and Arabidopsis thaliana, the ABCDE model genes of sea buckthorn were identified and some ABCDE model-related genes were selected for qRT-PCR analysis in sea buckthorn flowers and floral organs. Four B-type genes may be involved in the identity determination of floral organs in male flowers, and D-type genes may be involved in pistil development. It is hypothesized that ABCDE model genes may play an important role in the identity of sea buckthorn floral organs. This study analyzed the role of MADS-box gene family in the development of flower organs in sea buckthorn, which provides an important theoretical basis for understanding the regulatory mechanism of sex differentiation in sea buckthorn.

In recent years, landscape pattern optimization has been regarded as a cutting-edge science in various fields, and basin hydrology is no exception. Its effect on basin water purification has also been focused on. Based on the analysis of land use types and landscape patterns in the Danjiangkou Reservoir Basin, and combined with the determination of water quality indicators in the Danjiangkou Reservoir Basin, the relationship between the spatial pattern of Landscape Morphology and water quality was studied; It is found that among the basic characteristic indicators of many basins, the main influencing factors of water quality with high Variable importance for the projection (VIP>1) are IJI (Interspersion and Juxtaposition Index), COHE (Patch Cohesion Index), AI (Aggregation Index), PD (Patch Density), ED (Edge Density); Using PLSR (Partial Least Squares Regression) analysis, the main influencing factors of water quality were discussed. It was found that there was a significant negative regression relationship (Rc

The relationship between political economy and green innovation has been one of the most dynamic research in the field of green development recently. In this study, we conduct a scientometric analysis of 117 academic literature related to the field published from January 2005 to September 2023 using CiteSpace. The findings show an explosive growth trend of literature on this topic since 2020. Most of the literature used panel data to empirically explore the relationship between political economy and green innovation. Researchers have not only investigated the impact of political connections on green innovation, but also studied the mediating effects of these variables. The majority opinion is that political connections are detrimental to corporate green innovation. From the perspective of the sources of the literature, Chinese universities and scholars pay more attention to this field. Finally, we find that the literature related to political economy and green innovation is mainly published in energy-related journals.

Bisphenol AF (BPAF), an analogue of bisphenol A (BPA), is commonly found in manufacturing industries and known for its endocrine-disrupting properties. Despite potential similarities in adverse effects with BPA, limited toxicological data exist specifically for BPAF and its impact on male reproductive physiology. This mini-review aims to elucidate the influence of BPAF on the male reproductive system, focusing on estrogenic effects, effects on the hypothalamus-pituitary-gonad (HPG) axis, steroidogenesis, spermatogenesis, and transgenerational reproductive toxicity. Additionally, we outline the current insights into the potential mechanisms underlying BPAF-induced male reproductive disorders. BPAF exposure, either directly or maternally, has been associated with detrimental effects on male reproductive functions, including damage to the blood-testis barrier (BTB) structure, disruptions in steroidogenesis, testis dysfunction, decreased anogenital distance (AGD), and defects in sperm and semen quality. Mechanistically, altered gene expression in the HPG axis, deficits in the steroidogenesis pathway, activation of the aromatase pathway, cascade effects induced by reactive oxygen species (ROS), activation of ERK signaling, and immunological responses collectively contribute to the adverse effects of BPAF on the male reproductive system. Given the high prevalence of male reproductive issues and infertility, along with the widespread environmental distribution of bisphenols, this study provides valuable insights into the negative effects of BPAF. The findings underscore the importance of considering the safe use of this compound, urging further exploration and regulatory attention to decrease potential risks associated with BPAF exposure.

Abstract Fluorescent‐magneto nanoemitters have gained considerable attention for their applications in mechanical controlling‐assisted optical signaling. However, the incompatibility between magnetic and fluorescent components often leads to functional limitations in traditional magneto@fluorescence nanostructure. Herein, we introduce a new compact‐discrete spatial arrangement on a “fluorescence@magneto” core–shell nanostructure consisting of a close‐packed aggregation‐induced emission luminogen (AIEgen) core and a discrete magnetic shell. This structural design effectively eliminates the optical and magnetic interferences between the dual components by facilitating AIEgens loading in core region and reducing the magnetic feeding amount through effective exposure of the magnetic units. Thereby, the resulting magneto‐AIEgen nanoparticle (MANP) demonstrates “win‐win” performances: (i) high fluorescent intensity contributed by AIEgens stacking‐enhanced photoluminescence and reduced photons loss from the meager magnetic shell; (ii) marked magnetic activity due to magneto extraposition‐minimized magnetic shielding. Accordingly, the dual functions‐retained MANP provides a proof of concept for construction of an immunochromatographic sensing platform, where it enables bright fluorescent labeling after magnetically enriching and separating procalcitonin and lipoarabinomannan in clinical human serum and urine, respectively, for the clinical diagnosis of bacterial infections‐caused inflammation and tuberculosis. This study not only inspires the rational design of magnetic‐fluorescent nanoemitter but also highlights promising potential in magneto‐assisted point‐of‐care test and biomedicine applications.

Previous research investigating the correlation between prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and subsequent blood pressure (BP) in offspring has yielded limited and contradictory findings. This study was conducted to investigate the potential relationship between maternal PFAS levels during pregnancy and subsequent BP in early childhood. A total of 129 expectant mothers from the Shanghai Birth Cohort were included in the study. Using high-performance liquid chromatography/tandem mass spectrometry, we measured ten PFAS compounds in maternal plasma throughout the pregnancy. When the children reached the age of 4, we examined their systolic BP (SBP) and diastolic BP (DBP), along with mean arterial pressure (MAP) and pulse pressure (PP). Data interpretation employed multiple linear and logistic regression models, complemented by Bayesian kernel machine regression (BKMR).We found that the majority of PFAS concentrations remained stable during pregnancy. The linear and BKMR models indicated a positive relationship between the PFAS mixture in maternal plasma and offspring's DBP and MAP, with perfluorohexanesulphonic acid (PFHxS) having the most significant influence (PFHxS and DBP [first trimester:β=3.03, 95%CI: (1.01,5.05); second trimester: β=2.35, 95%CI: (0.94,3.75); third trimester: β=2.57, 95%CI:(0.80,4.34)]; MAP [first trimester:β=2.55, 95%CI: (0.64,4.45); second trimester: β=2.28, 95%CI: (0.95,3.61); third trimester: β=2.35, 95%CI:(0.68,4.01)]). Logistic regression highlighted an increased risk of prehypertension and hypertension in offspring with higher maternal PFHxS concentrations during all three trimesters [first trimester: OR=2.53, 95%CI:(1.11,5.79), second trimester: OR=2.05, 95%CI:(1.11,3.78), third trimester: OR=3.08, 95%CI:(1.40,6.79)]. A positive correlation was identified between the half-lives of PFAS and the odds ratio (OR) of prehypertension and hypertension in childhood (β=0.139, P=0.010). In conclusion, this research found maternal plasma PFAS concentrations to be positively associated with BP in offspring, with PFHxS showing the most significant influence. This correlation remained consistent throughout pregnancy, and this effect was proportional to the half-lives of PFAS.

Abstract Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid‐gestational age—the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case–control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.

Abstract Background Humans are widely exposed to perfluoroalkyl substances (PFAS), which have been found to be associated with various adverse birth outcomes. As blood pressure (BP) is an important parameter reflecting cardiovascular health in early life, it is necessary to investigate the association of PFAS exposure during early lifetime and BP in childhood. Therefore, we investigated the potential association between PFAS levels in umbilical cord blood and BP of the offspring at 4 years of age in a prospective cohort study. Methods PFAS in umbilical cord blood samples after birth were measured with high-performance liquid chromatography/tandem mass spectrometry in the Shanghai Birth Cohort. BP was measured at 4 years of age in the offspring. Multiple linear regression model was used to investigate the association between individual PFAS level and BP of the offspring. Bayesian kernel machine regression (BKMR) was used to analyze the relationship between the PFAS mixture and BP of the offspring, while weighted quantile sum (WQS) regression was utilized for sensitivity analysis. Results A total of 129 mother-child pairs were included in our analysis. In multiple linear regressions, we observed that long-chain PFAS, mainly including perfluorooctane sulfonate (PFOS), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUA), was negatively associated with systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial blood pressure (MAP). BKMR showed that an increase in umbilical cord blood PFAS mixture levels was significantly associated with a decrease in SBP, DBP and MAP [Estimated differences (SD): -0.433 (0.161); -0.437 (0.176); -0.382 (0.179), respectively]. The most important component in the association with SBP, DBP, and MAP was PFUA. PFDoA was found to be positively associated with SBP, DBP and MAP in both models. Sensitivity analysis with WQS regression showed consistent results. Conclusion Our findings suggested that umbilical blood PFAS exposure was negatively associated with BP in offspring at 4 years of age, including SBP, DBP, and MAP.

With the growing influence of slow population growth and population aging, China has established the birth policy and issued a series of documents to promote maternal and fetal health and improve the birth rate. With the increase in prevalence of birth defects, timely diagnosis and intervention in utero provide possibilities to reduce unnecessary abortions and offer better prognosis. Congenital heart disease (CHD), as one of the most common congenital birth defects, is the leading cause of mortality in patients aged

To meet the urgent need for a new design concept and solve the inaccuracy of existing performance prediction algorithms for high-speed turbomolecular pumps (TMPs), a new algorithm based on a novel twisted rotor blade is proposed. In this algorithm, the blade angle of the turbine rotor row progressively decreases from the root to the tip of the blade tooth. The feasibility and accuracy of the simulation algorithm were verified through experiments. The dependence of the simulation results on the number of simulated molecules was discussed. Both theoretical analysis and simulations confirmed the necessity of setting a twisted rotor blade in the turbine combined blade row. A comparative analysis on the performance of conventional straight-blade and twisted-blade structures based on the first-four stages of turbine combined blade rows of the F-63/55 TMP was conducted. The results indicated that the maximum pumping speed coefficient and maximum compression ratio of the optimised twisted-blade structure increased by 4.59% and 22.26%, respectively. This novel blade structure overcomes the limitations of the conventional straight-blade structure. Progressively decreasing the rotor blade angle from the root to the tip of the blade tooth is beneficial for improving the performance of TMPs. This study provides a new design concept and performance prediction algorithm for the structural optimisation of high-speed TMPs.

Using creativity to promote recreational services is crucial. Accordingly, creative linguistic landscapes (CLLs) are being used to improve visitors' experiences in some recreational zones. However, relevant research is still in its early stages. Therefore, this study was conducted. It summarized the leisure function categories and function evaluation indicators of CLLs in recreational zones respectively based on image materials and related online reviews. The leisure function outcomes of all CLL types were ranked using the fuzzy PROMETHEE method; based on this ranking, a CLL configuration optimization mode was suggested. The findings reveal the following. (1) Currently, there are mainly nine leisure function types of CLL in practice, although the type structure is severely imbalanced; there are 12 primary corresponding function evaluation indicators, although each of them draws significantly different attention. (2) There are notable variations among the outcomes of different types of functions of CLL: mood adjustment is the most advantageous function of CLL for leisure services, followed by emotional guidance and cognitive building functions; (3) According to the study findings, in the configuration of CLL, which aims at leisure function optimization, the "function focusing and coordinating mode (the superior functions of CLL are focused on and its various functions are coordinated)" should be adopted. The results provide meaningful lessons for the establishment of rational and effective CLL in recreational zones.

Introduction: This study investigates the geographical distribution and fractal characteristics of the medical service network in China, using the “Good Doctor website” as a case study.Methods: Data for this study were extracted from the Good Doctor website Health Community. A two-tiered hierarchical network model was developed to analyze the geographical distribution and fractal characteristics of the medical service network in China.Results: Results unveil the hierarchical nature of hospital distribution and the interconnectivity among healthcare institutions. Shandong Province as a central node within the national hospital network, and networks of secondary hospitals show significant self-similarity and scale-free properties.Discussion: The small world and fractal characteristics shed light on the rapid dissemination of medical information and the robustness of the healthcare network. The results offer a novel perspective for understanding and optimizing the distribution of medical resources, and help improve the efficiency of healthcare services supply.

Background Chemotherapy‐induced cardiovascular disease is a growing concern in the elderly population who have survived cancer, yet the underlying mechanism remains poorly understood. We investigated the role of ALKBH5 (AlkB homolog 5), a primary N6‐methyladenosine (m6A) demethylase, and its involvement in m6A methylation‐mediated regulation of targets in aging‐associated doxorubicin‐induced cardiotoxicity. Methods and Results To validate the relationship between doxorubicin‐induced cardiotoxicity and aging, we established young and old male mouse models. ALKBH5 expression was modulated through adeno‐associated virus 9 (in vivo), Lentivirus, and siRNAs (in vitro) to examine its impact on cardiomyocyte m6A modification, doxorubicin‐induced cardiac dysfunction, and remodeling. We performed mRNA sequencing, methylated RNA immunoprecipitation sequencing, and molecular assays to unravel the mechanism of ALKBH5‐m6A modification in doxorubicin‐induced cardiotoxicity. Our data revealed an age‐dependent increase in doxorubicin‐induced cardiac dysfunction, remodeling, and injury. ALKBH5 expression was elevated in aging mouse hearts, leading to reduced global m6A modification levels. Through mRNA sequencing and methylated RNA immunoprecipitation sequencing analyses, we identified ARID2 (AT‐rich interaction domain 2) as the downstream effector of ALKBH5‐m6A modulation in cardiomyocytes. Further investigations revealed that ARID2 modulates DNA damage response and enhances doxorubicin‐induced cardiomyocyte apoptosis. Conclusions Our findings provide insights into the role of ALKBH5‐m6A modification in modulating doxorubicin‐induced cardiac dysfunction, remodeling, and cardiomyocyte apoptosis in male mice. These results highlight the potential of ALKBH5‐targeted treatments for elderly patients with cancer in clinical settings.

In order to improve the comprehensive mechanical properties of Zn–3Mg alloy to meet application requirements of medical metal implants, spark plasma sintering (SPS) was adopted to prepare Zn–3Mg–xAg alloy (x = 0, 1, 1.5, 2, 2.5). Electron backscatter diffraction (EBSD)observation was adopted to investigate the growth twins in Zn–3Mg–xAg alloy, and then influences of Ag element on compactness, microstructure, tensile and compression properties of the zinc-based alloy were studied. Results showed that the length of growth twins first increased, then decreased with the increase of Ag element. Growth twins improved the ductility of alloy by turning the hard oriented grains into soft ones. The Zn–3Mg–1.5Ag alloy showed the best comprehensive mechanical properties due to the joint effect of solid solution strengthening, precipitation phase strengthening, fine grain strengthening and defect weakening. The tensile strength of Zn–3Mg–1.5Ag was 273.8 ± 16.9 MPa, which was 2.5 and 1.6 times that of Zn and Zn–3Mg respectively; the elongation was 10.67 ± 0.77%, which was 3.6 and 2.6 times that of Zn and Zn–3Mg respectively. Compressive strength of Zn–3Mg–1.5Ag was 543.7 ± 38.1 MPa, which was 3.8 times that of Zn; fracture strain of Zn–3Mg–1.5Ag was 20.49 ± 1.21%, which was 2 and 1.5 times of pure Zn and Zn–3Mg alloy.

The current study aimed to provide a precise assessment of the genetic parameters associated with growth and white spot syndrome virus (WSSV) resistance traits in Pacific white shrimp (Litopenaeus vannamei). This was achieved through a controlled WSSV challenge assay and the analysis of phenotypic values of five traits: body weight (BW), overall length (OL), body length (BL), tail length (TL), and survival hour post-infection (HPI). The analysis included test data from a total of 1017 individuals belonging to 20 families, of which 293 individuals underwent whole-genome resequencing, resulting in 18,137,179 high-quality SNP loci being obtained. Three methods, including pedigree-based best linear unbiased prediction (pBLUP), genomic best linear unbiased prediction (GBLUP), and single-step genomic BLUP (ssGBLUP) were utilized. Compared to the pBLUP model, the heritability of growth-related traits obtained from GBLUP and ssGBLUP was lower, whereas the heritability of WSSV resistance was higher. Both the GBLUP and ssGBLUP models significantly enhanced prediction accuracy. Specifically, the GBLUP model improved the prediction accuracy of BW, OL, BL, TL, and HPI by 4.77%, 21.93%, 19.73%, 19.34%, and 63.44%, respectively. Similarly, the ssGBLUP model improved prediction accuracy by 10.07%, 25.44%, 25.72%, 19.34%, and 122.58%, respectively. The WSSV resistance trait demonstrated the most substantial enhancement using both genomic prediction models, followed by body size traits (e.g., OL, BL, and TL), with BW showing the least improvement. Furthermore, the choice of models minimally impacted the assessment of genetic and phenotypic correlations. Genetic correlations among growth traits ranged from 0.767 to 0.999 across models, indicating high levels of positive correlations. Genetic correlations between growth and WSSV resistance traits ranged from (−0.198) to (−0.019), indicating low levels of negative correlations. This study assured significant advantages of the GBLUP and ssGBLUP models over the pBLUP model in the genetic parameter estimation of growth and WSSV resistance in L. vannamei, providing a foundation for further breeding programs.

Abstract This study proposes a novel, new ensemble model (NEM) designed to simulate the maximum water level increases caused by storm surges in a frequently cyclone‐affected coastal water of Hong Kong, China. The model relies on storm and water level data spanning 1978–2022. The NEM amalgamates three machine learning algorithms: Random Forest (RF), Gradient Boosting Decision Tree (GBDT), and XGBoost (XGB), employing a stacking technique for integration. Six parameters, determined using the Random Forest and Recursive Feature Elimination algorithms (RF‐RFE), are used as input features for the NEM. These parameters are the nearest wind speed, gale distance, nearest air pressure, minimum distance, maximum pressure drop within 24 hr, and large wind radius. Model assessment results suggest that the NEM exhibits superior performance over RF, GBDT, and XGB, delivering high stability and precision. It reaches a coefficient of determination (R2) up to 0.95 and a mean absolute error (MAE) that fluctuates between 0.08 and 0.20 m for the test data set. An interpretability analysis conducted using the SHapley Additive exPlanations (SHAP) method shows that gale distance and nearest wind speed are the most significant features for predicting peak water level increases during storm surges. The results of this study could provide practical implications for predictive models concerning storm surges. These findings present essential tools for the mitigation of coastal disasters and the improvement of marine disaster warning systems.

Left ventricular outflow tract obstruction (LVOTO), a major form of outflow tract malformation, accounts for a substantial portion of congenital heart defects (CHDs). Unlike its prevalence, the genetic architecture of LVOTO remains largely unknown. To unveil the genetic mutations and risk genes potentially associated with LVOTO, we enrolled a cohort of 106 LVOTO patients and 100 healthy controls and performed a whole-exome sequencing (WES). 71,430 rare deleterious mutations were found in LVOTO patients. By using gene-based burden testing, we further found 32 candidate genes enriched in LVOTO patient including known pathological genes such as GATA5 and GATA6. Most variants of 32 risk genes occur simultaneously rather exclusively suggesting polygenic inherence of LVOTO and 14 genes out of 32 risk genes interact with previously discovered CHD genes. Single cell RNA-seq further revealed dynamic expressions of GATA5, GATA6, FOXD3 and MYO6 in endocardium and neural crest lineage indicating the mutations of these genes lead to LVOTO possibly through different lineages. These findings uncover the genetic architecture of LVOTO which advances the current understanding of LVOTO genetics.

Ferroptosis is a newly discovered type of cell death mainly triggered by uncontrolled lipid peroxidation, and it could potentially have a significant impact on the development and progression of tetralogy of Fallot (TOF). Our project aims to identify and validate potential genes related to ferroptosis in TOF. We obtained sequencing data of TOF from the GEO database and ferroptosis-related genes from the ferroptosis database. We employed bioinformatics methods to analyze the differentially expressed mRNAs (DEmRNAs) and microRNAs between the normal control group and TOF group and identify DEmRNAs related to ferroptosis. Protein–protein interaction analysis was conducted to screen hub genes. Furthermore, a miRNA–mRNA–TF co-regulatory network was constructed to utilize prediction software. The expression of hub genes was further validated through quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). After conducting the differential gene analysis, we observed that in TOF, 41 upregulated mRNAs and three downregulated mRNAs associated with ferroptosis genes were found. Further Gene Ontology/Kyoto Encyclopedia of Genes and Genomes analysis revealed that these genes were primarily involved in molecular functions and biological processes related to chemical stress, oxidative stress, cellular response to starvation, response to nutrient levels, cellular response to external stimulus, and cellular response to extracellular stimulus. Furthermore, we constructed a miRNA–mRNA–TF co-regulatory network. qRT-PCR analysis of the right ventricular tissues from human cases showed an upregulation in the mRNA levels of KEAP1 and SQSTM1. Our bioinformatics analysis successfully identified 44 potential genes that are associated with ferroptosis in TOF. This finding significantly contributes to our understanding of the molecular mechanisms underlying the development of TOF. Moreover, these findings have the potential to open new avenues for the development of innovative therapeutic approaches for the treatment of this condition.

The lack of diagnostic taxonomic characteristics in some species complexes leave the species delimitation of Oxytropis DC. unresolved. Seed morphological features have proved to be useful diagnostic and taxonomic characteristics in Fabaceae. However, there are few systematic studies on the seed characteristics of Oxytropis. Here, we used scanning electron and stereoscopic microscopy to investigate the seed characteristics of 35 samples obtained from 21 Oxytropis species from northwest China. Our examination showed two main types of hilum positions, terminal and central, and five different types of seed shapes: prolonged semielliptic, reniform, prolonged reniform, quadratic, and cardiform. Seven different sculpturing patterns were identified: scaled, regulated, lophate with stellated testa cells, simple reticulate, rough, compound reticulate, and lophate with rounded testa cells. The seeds ranged from 1.27 to 2.57 mm in length and from 1.18 to 2.02 mm in width, and the length-to-width ratio ranged from 0.89 to 1.55 mm. The seed shape was constant within species and was useful for species delimitation within the genus Oxytropis when combined with other macroscopic traits. In contrast, the sculpturing patterns were highly variable at the species level and could not be used for species identification. Results of the cluster analysis and principal component analysis (PCA) indicated that the seed traits of Oxytropis species are useful for taxa identification at the species level, but have low taxonomic value at the section level.

Abstract Background Current evidence relating birthweight and gestational age to cardiovascular risk is conflicting. Whether these factors have independent or interactive impacts on cardiovascular parameters during early childhood remains unclear. The goal of this study was to explore whether there were any independent and interactive effects of gestational age and birthweight on blood pressure, left ventricle (LV) structure, and function in 4 years old. Methods This study included 1194 children in the Shanghai Birth Cohort from 2013 to 2016. Information about the mothers and children was recorded at time of birth using a questionnaire. Follow-up measurements, including anthropometric, blood pressure, and echocardiography, were taken between 2018 and 2021, when the children were 4 years old. Multiple linear or logistic regressions and restricted cubic spline were used to explore the association of birthweight and gestational age with cardiovascular measurements. Results Gestational age had a significant negative correlation with both systolic blood pressure [β = − 0.41, 95% CI: (− 0.76, − 0.07)] and mean arterial pressure [β = − 0.36, 95%CI: (− 0.66, − 0.07)]. The risk of prehypertension decreased with increased gestational age [OR = 0.54, 95% CI: (0.32, 0.93)]. The relationship between birthweight with blood pressure was U-shape (P for non-linear

Abstract Background To better assist with the design of future clinical trials for Alzheimer’s disease (AD) and aid in our understanding of the disease’s symptomatology, it is essential to clarify what roles β-amyloid (Aβ) plaques and tau tangles play in longitudinal tau accumulation inside and outside the medial temporal lobe (MTL) as well as how age, sex, apolipoprotein E (APOE) ε4 (APOE-ε4), and Klotho-VS heterozygosity (KL-VShet) modulate these relationships. Methods We divided the 325 Aβ PET-positive (A+) participants into two groups, A+/T− (N = 143) and A+/T+ (N = 182), based on the threshold (1.25) of the temporal meta-ROI 18F-flortaucipir (FTP) standardized uptake value ratio (SUVR). We then compared the baseline and slopes of A+/T− and A+/T+ individuals’ Aβ plaques and temporal meta-ROI tau tangles with those of A−/T− cognitively unimpaired individuals (N = 162) without neurodegeneration. In addition, we looked into how baseline Aβ and tau may predict longitudinal tau increases and how age, sex, APOE-ε4, and KL-VShet affect these associations. Results In entorhinal, amygdala, and parahippocampal (early tau-deposited regions of temporal meta-ROI), we found that baseline Aβ and tau deposition were positively linked to more rapid tau increases in A+/T− participants. However, in A+/T+ individuals, the longitudinal tau accumulation in fusiform, inferior temporal, and middle temporal cortices (late tau-deposited regions of temporal meta-ROI) was primarily predicted by the level of tau tangles. Furthermore, compared to older participants (age ≥ 65), younger individuals (age < 65) exhibited faster Aβ-dependent but slower tau-related tau accumulations. Additionally, compared to the KL-VShet− group, KL-VShet+ individuals showed a significantly lower rate of tau accumulation associated with baseline entorhinal tau in fusiform and inferior temporal regions. Conclusion These findings offer novel perspectives to the design of AD clinical trials and aid in understanding the tau accumulation inside and outside MTL in AD. In particular, decreasing Aβ plaques might be adequate for A+/T− persons but may not be sufficient for A+/T+ individuals in preventing tau propagation and subsequent downstream pathological changes associated with tau.

Cell free DNA is produced through a non-random process. Here, the authors use orientation-aware fragmentation analysis to identify DNA methylation as a regulator of nuclease function.

Abstract Extracellular matrix (ECM) not only serves as a support for tumor cell but also regulates cell–cell or cell–matrix cross-talks. Collagens are the most abundant proteins in ECM. Several studies have found that certain collagen genes were overexpressed in gastric cancer (GC) tissues and might serve as potential biomarkers and therapeutic targets in GC patients. However, the expression patterns of all collagen family genes in GC tissue and their functions are still not clear. With RNA sequencing (RNA-Seq) data, microarray data, and corresponding clinical data obtained from TCGA, GTEx, and GEO databases, bioinformatics analyses were performed to investigate the correlation between the expression patterns of collagen family genes and GC progression. We found that quite many of the collagen family genes were overexpressed in GC tissues. The increase in mRNA expression of most of these overexpressed collagen genes happened between T1 and T2 stage, which indicates the significance of collagens in tumor enlargement of GC. Notably, the mRNA expressions of these differentially expressed collagens genes were highly positively correlated. The elevated expression of a large number of collagen genes in early T stage might greatly change the composition and structure organization of ECM, contributing to ECM remodeling in GC progression.

Imaging non-repetitive loci in living cells remains challenging. Here, the authors engineered an inducible system whereby biomolecular assemblies can be guided to specific genomic loci by a nuclease-defective Cas9, allowing the simultaneous imaging and manipulation of the loci.

As a highly productive and biologically diverse ecosystem, wetlands provide unique habitat for a wide array of plant and animal species. Owing to the strong disturbance by human activities and climate change, wetland degradation and fragmentation have become a common phenomenon across the globe. The Guangdong–Hong Kong–Macao Greater Bay Area (GBA) is a typical case. The GBA has experienced explosive growth in the population and economy since the early 1980s, which has resulted in complicated transitions between wetlands and non-wetlands. However, our knowledge about the transformation paths, associated drivers, and ecological influence of the GBA’s wetlands is still very limited. Taking advantage of the land use maps generated from Landsat observations over the period of 1980–2020, here, we quantified the spatiotemporal transformation paths of the GBA’s wetlands and analyzed the associated drivers and ecological influence. We found that the dominant transformation path between wetland and non-wetland was from wetland to built-up land, which accounted for 98.4% of total wetland loss. The primary transformation path among different wetland types was from coastal shallow water and paddy land to reservoir/pond, with the strongest transformation intensity in the 1980s. The driving forces behind the wetland change were found to vary by region. Anthropogenic factors (i.e., population growth and urbanization) dominated in highly developed cities, while climate factors and aquaculture had a greater influence in underdeveloped cities. The findings presented in this study will provide a reference for wetland management and planning in the GBA.

Abstract Background Heterotaxy syndrome (HTX) is caused by aberrant left–right patterning early in embryonic development, which results in abnormal positioning and morphology of the thoracic and abdominal organs. Currently, genetic testing discerns the underlying genetic cause in less than 20% of sporadic HTX cases, indicating that genetic pathogenesis remains poorly understood. In this study, we aim to garner a deeper understanding of the genetic factors of this disease by documenting the effect of different matrix metalloproteinase 21 (MMP21) variants on disease occurrence and pathogenesis. Methods Eighty-one HTX patients with complex congenital heart defects and 89 healthy children were enrolled, and we investigated the pathogenetic variants related to patients with HTX by exome sequencing. Zebrafish splice-blocking Morpholino oligo-mediated transient suppression assays were performed to confirm the potential pathogenicity of missense variants found in these patients with HTX. Results Three MMP21 heterozygous non-synonymous variants (c.731G > A (p.G244E), c.829C > T (p.L277F), and c.1459A > G (p.K487E)) were identified in three unrelated Chinese Han patients with HTX and complex congenital heart defects. Sanger sequencing confirmed that all variants were de novo. Cell transfection assay showed that none of the variants affect mRNA and protein expression levels of MMP21. Knockdown expression of mmp21 by splice-blocking Morpholino oligo in zebrafish embryos revealed a heart looping disorder, and mutant human MMP21 mRNA (c.731G > A, c.1459A > G, heterozygous mRNA (wild-type&c.731G > A), as well as heterozygous mRNA (wild-type& c.1459A > G) could not effectively rescue the heart looping defects. A patient with the MMP21 p.G244E variant was identified with other potential HTX-causing missense mutations, whereas the patient with the MMP21 p.K487E variant had no genetic mutations in other causative genes related to HTX. Conclusion Our study highlights the role of the disruptive heterozygous MMP21 variant (p.K487E) in the etiology of HTX with complex cardiac malformations and expands the current mutation spectrum of MMP21 in HTX.

Abstract Background Chasmogamous (CH)–cleistogamous (CL) dimorphic flowers are developed in Viola prionantha. However, the environmental and genetic factors necessary for the CH–CL transition are unknown. Results In the present work, short-day (SD) conditions induced CH flowers, whereas long days (LDs) triggered CL flowers in V. prionantha. Compared to fully developed CH flowers, CL flowers had less mature stamens, no nectar glands, and immature petals. Comparative transcriptomics revealed differentially expressed genes (DEGs) during CL and CH development. Core genes in the photoperiod pathway, such as V. prionantha orthologs of GIGANTEA (GI), CONSTANS (CO), and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1), which promote floral induction, were highly expressed in CL flowers, whereas UNUSUAL FLORAL ORGANS (UFO) and B-class MADS-box genes for floral organ identity and development showed an opposite alteration. Moreover, genes in the glycolytic process, sucrose metabolic process, and fatty acid biosynthetic process were all highly expressed in CH flowers. Interestingly, V. prionantha orthologs of the B-class MADS-box genes APETALA3 (AP3) and PISTILLATA (PI) might relate to these sugar–fatty acid processes and were co-expressed with GAIP-B-like and YABBY5 (YAB5), which regulate the development of the petal, stamen, and nectary. Compared to CH flowers, DEGs and hub genes in the most significantly correlated modules of the gene co-expression network, which are involved in abiotic and biotic responses, were upregulated in CL flowers. Conclusions We proposed an integrative model for transcription regulation of genes in the photoperiod pathway, floral organ development, stress response, and sugar–fatty acid processes to determine CH–CL flower development in V. prionantha. Particularly, under LDs, activated GI may induce genes involved in the stress-response pathways, and then downregulated AP3 and PI or UFO to inhibit the sugar–fatty acid metabolic processes, together forming CL flowers. In contrast, CH flowers were produced under SDs. This work provides novel insights into the developmental evolution of dimorphic flowers in Viola.

To explore the performance differences among offspring obtained by the intra- and inter-strain crosses, strain A with outstanding WSSV resistance and strain B with outstanding growth of Litopenaeus vannamei were used to construct four experimental groups in a complete diallel cross. 27 growth-related phenotypic traits and WSSV resistance represented by the surviving hours post-infection were obtained via the growth and the virus challenge test. Mixed linear model along with physical pedigree were utilized to calculate the least squares means, correlations, heritability and heterosis. The results showed that crossbreeding can realize character complementation of advantage strain. The performance of WSSV resistance was ranked AA> BA> AB> BB, and the reciprocal crosses performed significantly better than intra-strain group BB. Most growth-related traits in two reciprocal cross groups were also significantly better than those in AA group. Comparisons between the two reciprocal crosses showed that BA cross was better than AB in terms of WSSV resistance and growth. Heterosis of WSSV resistance in BA cross was 5.74∼10.18% greater than that in AB, meanwhile the absolute weight gain rate of BA cross was 4.83% higher than that of AB. The heritability estimates of body length and body weight were 0.0278 and 0.339, both of which reached medium level. The genetic and phenotypic correlations among growth-related traits were from 0.36 to 0.99 and 0.32 to 0.99, respectively. In term of WSSV resistance, the heritability estimate was 0.135 ± 0.082. The genetic and phenotypic correlations between WSSV resistance and growth-related traits were from − 0.034 to − 0.573 and − 0.001 to − 0.202, respectively. The results showed that hybrid offspring obtained by crossing female parents with outstanding WSSV resistance and male parents with outstanding growth culminated in a superior heterosis in both traits. This study provides basic reference data for L. vannamei breeding of new strains that are disease resistant and fast-growing.

The aim of this study was to clarify the mechanism by which thinning alters stand structure and affects forest productivity by characterizing changes in stand quantitative maturity age, stand diameter distribution, structural heterogeneity, and forest productivity of Chinese fir plantations at different thinning times and intensities. Our findings provide insights into how the density of stands could be modified to enhance the yield and timber quality of Chinese fir plantations. The significance of differences in individual tree volume, stand volume, and timber merchantable volume was determined using one-way analysis of variance and post hoc Duncan tests. The stand quantitative maturity age was obtained using the Richards equation. The quantitative relationship between stand structure and productivity was determined using a generalized linear mixed model. We found that (1) the quantitative maturity age of Chinese fir plantations increased with thinning intensity, and the quantitative maturity age was much greater under commercial thinning than under pre-commercial thinning. (2) Individual tree volume and the proportion of medium-sized and large-sized timber merchantable volume increased with stand thinning intensity. Thinning promoted increases in stand diameter. pre-commercially thinned stands were dominated by medium-diameter trees when the quantitative maturity age was reached, whereas commercially thinned stands were dominated by large-diameter trees. The living trees volume will decrease immediately after thinning, and then it will gradually increase with the age of the stand. When the stand volume included both living trees volume and thinned volume, thinned stands increased stand volume compared with unthinned stands. In pre-commercial thinning stands, the greater the intensity of thinning, the greater the increase in stand volume, and the opposite was true for commercial thinning. (3) Thinning also reduced heterogeneity in stand structure, which was lower after commercial thinning than after pre-commercial thinning. The productivity of pre-commercially thinned stands increased with thinning intensity, whereas that of commercially thinned stands decreased with thinning intensity. (4) The structural heterogeneity of pre-commercially and commercially thinned stands was negatively and positively correlated with forest productivity, respectively. In the Chinese fir plantations in the hilly terrain of the northern Chinese fir production area, when pre-commercial thinning was performed in the ninth year to a residual density of 1750 trees per hectare, the stand quantitative maturity age was reached in year 30, medium-sized timber accounted for 75.2% of all trees, and the stand volume was 667.9 m3 per hectare. This thinning strategy is favorable for producing medium-sized Chinese fir timber. When commercial thinning was performed in year 23, the optimal residual density was 400 trees per hectare. When the stand quantitative maturity age was reached in year 31, large-sized timber accounted for 76.6% of all trees, and the stand volume was 574.5 m3 per hectare. This thinning strategy is favorable for producing large-sized Chinese fir timber.