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Sleep disorders are among the common comorbidities of autism spectrum disorder (ASD), which not only affect the daily life and learning ability of children but may also exacerbate other symptoms of ASD, seriously impacting the quality of life of children and their families. Given this, understanding the neurobiological mechanisms of sleep disorders in children with ASD has significant research value for developing effective intervention strategies. Melatonin, 5-HT, and orexin are key neurotransmitters that regulate the sleep-wake cycle. Through in-depth analysis of the biological functions and regulatory pathways of these neurotransmitters, new perspectives may be provided for personalized treatment of sleep disorders in children with ASD. This article reviews the research progress on melatonin, 5-HT, and orexin in sleep disorders among children with autism spectrum disorder, focusing on exploring the mechanisms of these key neurotransmitters in sleep disorders of children with ASD and how they affect the sleep-wake cycle, providing a theoretical basis for improving the sleep quality of children with ASD.

Abstract Background and Aim Currently, SARS‐CoV‐2 is still spreading rapidly and globally. A large proportion of patients with COVID‐19 developed liver injuries. The human‐induced pluripotent stem cell (iPSC)‐derived hepatocytes recapitulate primary human hepatocytes and have been widely used in studies of liver diseases. Methods To explore the susceptibility of hepatocytes to SARS‐CoV‐2, we differentiated iPSCs to functional hepatocytes and tried infecting them with different MOI (1, 0.1, 0.01) of SARS‐CoV‐2. Results The iPSC‐derived hepatocytes are highly susceptible to virus infection, even at 0.01 MOI. Other than the ancestral strain, iHeps also support the replication of SARS‐CoV‐2 variants including alpha, beta, theta, and delta. More interestingly, the ACE2 expression significantly upregulated after infection, suggesting a vicious cycle between virus infection and liver injury. Conclusions The iPSC‐derived hepatocytes can support the replication of SARS‐CoV‐2, and this platform could be used to investigate the SARS‐CoV‐2 hepatotropism and hepatic pathogenic mechanisms.

In most real world rehabilitation training, patients are trained to regain motion capabilities with the aid of functional/epidural electrical stimulation (FES/EES), under the support of gravity-assist systems to prevent falls. However, the lack of motion analysis dataset designed specifically for rehabilitation-related applications largely limits the conduct of pilot research. We provide an open access dataset, consisting of multimodal data collected via 16 electromyography (EMG) sensors, 6 inertial measurement unit (IMU) sensors, and 230 insole pressure sensors (IPS) per foot, together with a 26-sensor motion capture system, under different MOVEments and POstures for Rehabilitation Training (MovePort). Data were collected under diverse experimental paradigms. Twenty four participants first imitated multiple normal and abnormal body postures including (1) normal standing still, (2) leaning forward, (3) leaning back, and (4) half-squat, which in practical applications, can be detected as feedback to tune the parameters of FES/EES and gravity-assist systems to keep patients in a target body posture. Data under imitated abnormal gaits, e.g., (1) with legs raised higher under excessive electrical stimulation, and (2) with dragging legs under insufficient stimulation, were also collected. Data under normal gaits with low, medium and high speeds are also included. Pathological gait data from a subject with spastic paraplegia further increases the clinical value of our dataset. We also provide source codes to perform both intra- and inter-participant motion analyses of our dataset. We expect our dataset can provide a unique platform to promote collaboration among neurorehabilitation engineers.

Nanoplastic contamination has been of intense concern by virtue of the potential threat to human and ecosystem health. Animal experiments have indicated that exposure to nanoplastics (NPs) can deposit in the liver and contribute to hepatic injury. To explore the mechanisms of hepatotoxicity induced by polystyrene-NPs (PS-NPs), mice and AML-12 hepatocytes were exposed to different dosages of 20 nm PS-NPs in this study. The results illustrated that in vitro and in vivo exposure to PS-NPs triggered excessive production of reactive oxygen species and repressed nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway and its downstream antioxidase expression, thus leading to hepatic oxidative stress. Moreover, PS-NPs elevated the levels of NLRP3, IL-1β and caspase-1 expression, along with an activation of NF-κB, suggesting that PS-NPs induced hepatocellular inflammatory injury. Nevertheless, the activaton of NRF2 signaling by tert-butylhydroquinone mitigated PS-NPs-caused oxidative stress and inflammation, and inbihited NLRP3 and caspase-1 expression. Conversely, the rescuing effect of NRF2 signal activation was dramatically supressed by treatment with NRF2 inhibitor brusatol. In summary, our results demonstrated that NRF2-NLRP3 pathway is involved in PS-NPs-aroused hepatotoxicity, and the activation of NRF2 signaling can protect against PS-NPs-evoked liver injury. These results provide novel insights into the hepatotoxicity elicited by NPs exposure.

Infertility is a growing health concern among many couples worldwide. Men account for half of infertility cases. CatSper, a sperm-specific Ca2+ channel, is expressed on the cell membrane of mammalian sperm. CatSper plays an important role in male fertility because it facilitates the entry of Ca2+ necessary for the rapid change in sperm motility, thereby allowing it to navigate the hurdles of the female reproductive tract and successfully locate the egg. Many pollutants present in the environment have been shown to affect the functions of CatSper and sperm, which is a matter of capital importance to understanding and solving male infertility issues. Environmental pollutants can act as partial agonists or inhibitors of CatSper or exhibit a synergistic effect. In this article, we briefly describe the structure, functions, and regulatory mechanisms of CatSper, and discuss the body of literature covering the effects of environmental pollutants on CatSper.

It is crucial to employ scientifically sound models for assessing the quality of the ecological environment and revealing the strengths and weaknesses of ecosystems. This process is vital for identifying regional ecological and environmental issues and devising relevant protective measures. Among the widely acknowledged models for evaluating ecological quality, the ecological index (EI) and remote sensing ecological index (RSEI) stand out; however, there is a notable gap in the literature discussing their differences, characteristics, and reasons for selecting either model. In this study, we focused on Fangshan District, Beijing, China, to examine the differences between the two models from 2017 to 2021. We summarized the variations in evaluation indices, importance, quantitative methods, and data acquisition times, proposing application scenarios for both models. The results indicate that the ecological environment quality in Fangshan District, Beijing, remained favorable from 2017 to 2021. There was a discernible trend of initially declining quality followed by subsequent improvement. The variation in the calculation results is evident in the overall correlation between the RSEI and EI. Particularly noteworthy is the significantly smaller correlation between EI and the RSEI in 2021 than in the other two years. This discrepancy is attributed to shifts in the contribution of the evaluation indices within the RSEI model. The use of diverse quantitative methods for evaluating indicators has resulted in several variations. Notably, the evaluation outcomes of the EI model exhibit a stronger correlation with land cover types. This correlation contributes to a more pronounced fluctuation in RSEI levels from 2017 to 2021, with the EI model's evaluation results in 2019 notably surpassing those of the RSEI model. Ultimately, the most prominent disparities lie in the calculation results for water areas and construction land. The substantial difference in water areas is attributed to the distinct importance assigned to evaluation indicators between the two models. Moreover, the notable difference in construction land arises from the use of different quantification methods for evaluation indicators. In general, the EI model has suggested to be more comprehensive and effectively captures the annual comprehensive status of the ecological environment and the multiyear change characteristics of the administrative region. On the other hand, RSEI models exhibit greater flexibility and ease of implementation, independent of spatial and temporal scales. These findings contribute to a clearer understanding of the models' advantages and limitations, offering guidance for decision makers and valuable insights for the improvement and development of ecological environmental quality evaluation models.

Surface electromyography (sEMG) is commonly used as an interface in human–machine interaction systems due to their high signal-to-noise ratio and easy acquisition. It can intuitively reflect motion intentions of users, thus is widely applied in gesture recognition systems. However, wearable sEMG-based gesture recognition systems are susceptible to changes in environmental noise, electrode placement, and physiological characteristics. This could result in significant performance degradation of the model in inter-session scenarios, bringing a poor experience to users. Currently, for noise from environmental changes and electrode shifting from wearing variety, numerous studies have proposed various data-augmentation methods and highly generalized networks to improve inter-session gesture recognition accuracy. However, few studies have considered the impact of individual physiological states. In this study, we assumed that user exercise could cause changes in muscle conditions, leading to variations in sEMG features and subsequently affecting the recognition accuracy of model. To verify our hypothesis, we collected sEMG data from 12 participants performing the same gesture tasks before and after exercise, and then used Linear Discriminant Analysis (LDA) for gesture classification. For the non-exercise group, the inter-session accuracy declined only by 2.86%, whereas that of the exercise group decreased by 13.53%. This finding proves that exercise is indeed a critical factor contributing to the decline in inter-session model performance.

Abstract Background With the development of whole-genome sequencing technology, non-invasive prenatal testing (NIPT) has been applied gradually to screen chromosomal microdeletions and microduplications that cannot be detected by traditional karyotyping. However, in NIPT, some false positives and false negatives occur. This study aimed to investigate the applicability of extended NIPT (NIPT-PLUS) in the detection of chromosomal aneuploidy and microdeletion/microduplication syndrome (MMS). Methods A total of 452 pregnancies that underwent prenatal diagnostic testing (amniocentesis or chorionic villus sampling) by chromosomal microarray analysis (CMA), were screened by NIPT-PLUS from the peripheral blood sample of the pregnant women. The results of the two tested items were compared and analysed. Results Of the 452 cases, 335 (74.12%) had positive CMA results, and 117 (25.88%) had no abnormal results. A total of 86 cases of trisomy 21, 18 and 13 and sex chromosome aneuploidy (SCA) were detected by CMA and NIPT-PLUS, with a detection rate of 96.51% (83/86). Among them, the detection rates of T18, T13; 47, XXY; 47, XXX and 47 XYY were 100%, and the detection rates of T21 and 45 XO were 96.55% and 90%, respectively. The detection sensitivity of rare chromosomal trisomy (RAT) was 80% (4/5). The positive predictive values of NIPT-PLUS for chromosome aneuploidy T21, T18 and T13 and for SCA and RAT were 90.32%, 87.50%, 25.00%, 88.89% and 50%, respectively. A total of 249 cases (74.32%) of chromosomal MMS were detected by CMA. The detection rate of NIPT-PLUS was 63.86% (159/249), and 90 cases (36.14%) were missed. The larger the MMS fragment, the higher the NIPT-PLUS detection sensitivity. In addition, most small fragments were of maternal origin. Conclusion The comparison between the CMA and NIPT-PLUS techniques shows that NIPT-PLUS has high sensitivity for detecting chromosomal aneuploidy and chromosomal copy number variations (CNVs) with fragments > 5 M. However, the sensitivity of CNV for fragments

Urban green–blue space (UGBS) plays a crucial role in Chinese cities, occupying more than half of the built-up areas. Understanding the spatiotemporal dynamics and driving factors of UGBS in central Nanjing during rapid urbanization is important for studying UGBS evolution in high-density urban-area environments, providing a fundamental basis for related research and policy formulation. This study utilized remote sensing images to estimate the extent of UGBS from 2000 to 2020 and analyzed the evolution using the intensity of area change, a land transfer matrix, the multi-order adjacency index, and a boosted regression tree model. This study revealed the spatiotemporal dynamics and driving factors of UGBSs in central Nanjing from 2000 to 2020: (1) between 2000 and 2020, there was a 4.0% net increase in the total area of UGBSs in central Nanjing. (2) UGBS primarily showed marginal-type expansion, accompanied by proximity-type expansion. Spatially, new green–blue patches tended to cluster around large pre-existing natural green–blue patches. Furthermore, the expansion of UGBS shifted from the urban periphery to the urban interior. (3) Natural factors exerted a greater influence (88.3%) than socioeconomic factors (11.7%) on the expansion of UGBS. Average annual radiation (43.4%), elevation (16.5%), slope (15%), aspect (13.4%), and population density (2.8%) were the primary driving factors. Our results contribute to understanding changes in UGBS and the driving factors behind these changes, thereby providing support for the future planning, protection, and sustainable development of UGBS.

In recent years, nanoplastics (NPs) and triclosan (TCS, a pharmaceutical and personal care product) have emerged as environmental pollution issues, and their combined presence has raised widespread concern regarding potential risks to organisms. However, the combined toxicity and mechanisms of NPs and TCS remain unclear. In this study, we investigated the toxic effects of polystyrene NPs and TCS and their mechanisms on KGN cells, a human ovarian granulosa cell line. We exposed KGN cells to NPs (150 μg/mL) and TCS (15 μM) alone or together for 24 hours. Co-exposure significantly reduced cell viability. Compared with exposure to NPs or TCS alone, co-exposure increased reactive oxygen species (ROS) production. Interestingly, co-exposure to NPs and TCS produced synergistic effects. We examined the activity of superoxide dismutase (SOD) and catalase (CAT), two antioxidant enzymes; it was significantly decreased after co-exposure. We also noted an increase in the lipid oxidation product malondialdehyde (MDA) after co-exposure. Furthermore, co-exposure to NPs and TCS had a more detrimental effect on mitochondrial function than the individual treatments. Co-exposure activated the NRF2–KEAP1–HO-1 antioxidant stress pathway. Surprisingly, the expression of SESTRIN2, an antioxidant protein, was inhibited by co-exposure treatments. Co-exposure to NPs and TCS significantly increased the autophagy-related proteins LC3B-II and LC3B-Ⅰ and decreased P62. Moreover, co-exposure enhanced CASPASE-3 expression and inhibited the BCL-2/BAX ratio. In summary, our study revealed the synergistic toxic effects of NPs and TCS in vitro exposure. Our findings provide insight into the toxic mechanisms associated with co-exposure to NPs and TCS to KGN cells by inducing oxidative stress, activations of the NRF2-KEAP1-HO-1 pathway, autophagy, and apoptosis.

Abstract Whole -genome sequencing projects of millions of subjects contain enormous genotypes, entailing a huge memory burden and time for computation. Here, we present GBC, a toolkit for rapidly compressing large-scale genotypes into highly addressable byte-encoding blocks under an optimized parallel framework. We demonstrate that GBC is up to 1000 times faster than state-of-the-art methods to access and manage compressed large-scale genotypes while maintaining a competitive compression ratio. We also showed that conventional analysis would be substantially sped up if built on GBC to access genotypes of a large population. GBC’s data structure and algorithms are valuable for accelerating large-scale genomic research.

Against the background of global warming, urban blue–green spaces (UBGS) are important carbon sequestration (CS) carriers that can reduce carbon emissions. However, previous studies on urban CS were mostly limited to urban green or blue spaces separately and lack a comprehensive consideration of the synergistic impact of UBGS on CS. In addition, research on the driving mechanism between urban blue–green spatial patterns (UBGSP) and CS has so far been insufficient. Therefore, in this study, we explored the correlation between UBGSP and CS, identified the affecting UBGSP factors, and proposed suggestions for planning design. We identified the UBGS of the central city of Nanjing based on Landsat-8, calculated the CS using the Carnegie-Ames-Stanford approach (CASA), and analyzed the relationship between the UBGSP and CS at both class and landscape levels by establishing sets of UBGSP indicators. At the class level, the percentage of landscape and aggregation index have positive effects on CS, whereas the landscape division and shape indexes have negative effects. Moreover, edge density and area-weighted patch fractal dimension do not correlate with CS. At the landscape level, connectance can promote the CS of UBGS. Finally, we found that the largest patch index, edge density, Shannon’s evenness index, patch cohesion index, and contagion have no significant effects. The results of this study contribute to the systematic optimization of UBGSPs, promote the integrated development of UBGSs, and provide references for urban planning practices and resource management.

Protein kinase-mediated phosphorylation plays a critical role in many biological processes. Here the authors develop a trans-omics-based algorithm called Central Kinase Inference to integrate quantitative transcriptomic and phosphoproteomic data, finding that PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest.

Plastic particle pollution poses an emerging threat to ecological and human health. Laboratory animal studies have illustrated that nano-sized plastics can accumulate in the testis and cause testosterone deficiency and spermatogenic impairment. In this study, TM3 mouse Leydig cells were in vitro exposed to polystyrene nanoparticles (PS-NPs, size 20 nm) at dosages of 50, 100 and 150 μg/mL to investigate their cytotoxicity. Our results demonstrated that PS-NPs can be internalized into TM3 Leydig cells and led to a concentration-dependent decline in cell viability. Furthermore, PS-NPs stimulation amplified ROS generation and initiated cellular oxidative stress and apoptosis. Moreover, PS-NPs treatment affected the mitochondrial DNA copy number and collapsed the mitochondrial membrane potential, accompanied by a disrupted energy metabolism. The cells exposed to PS-NPs also displayed a down-regulated expression of steroidogenesis-related genes StAR, P450scc and 17β-HSD, along with a decrease in testosterone secretion. In addition, treatment with PS-NPs destructed plasma membrane integrity, as presented by increase in lactate dehydrogenase release and depolarization of cell membrane potential. In summary, these data indicated that exposure to PS-NPs in vitro produced cytotoxic effect on Leydig cells by inducing oxidative injury, mitochondrial impairment, apoptosis, and cytomembrane destruction. Our results provide new insights into male reproductive toxicity caused by NPs.

Increasing evidence shows that genetic interaction across the entire genome may explain a non-trivial fraction of genetic diseases. Digenic interaction is the simplest manifestation of genetic interaction among genes. However, systematic exploration of digenic interactive effects on the whole genome is often discouraged by the high dimension burden. Thus, numerous digenic interactions are yet to be identified for many diseases. Here, we propose a Digenic Interaction Effect Predictor (DIEP), an accurate machine-learning approach to identify the genome-wide pathogenic coding gene pairs with digenic interaction effects. This approach achieved high accuracy and sensitivity in independent testing datasets, outperforming another gene-level digenic predictor (DiGePred). DIEP was also able to discriminate digenic interaction effect from bi-locus effects dual molecular diagnosis (pseudo-digenic). Using DIEP, we provided a valuable resource of genome-wide digenic interactions and demonstrated the enrichment of the digenic interaction effect in Mendelian and Oligogenic diseases. Therefore, DIEP will play a useful role in facilitating the genomic mapping of interactive causal genes for human diseases.

As emerging organic contaminants, per- and polyfluoroalkyl substances (PFASs) have aroused worldwide concern due to their environmental persistence, ubiquitous presence, bioaccumulation, and potential toxicity. It has been demonstrated that PFASs can accumulate in human body and cause multiple adverse health outcomes. Notably, PFASs have been detected in the semen of human, posing a potential hazard to male fecundity. This article reviews the evidence about the toxic effects of exposure to PFASs on male reproduction, focusing on the sperm quality. Epidemiological studies showed that PFASs, such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were adversely associated with the semen parameters in humans, including sperm count, morphology and motility. Experimental results also confirmed that PFAS exposure led to testicular and epididymal damage, therefore impairing spermatogenesis and sperm quality. The mechanisms of reproductive toxicity of PFASs may be involved in blood-testosterone barrier destruction, testicular apoptosis, testosterone synthesis disorder, and membrane lipid composition alteration, oxidative stress and Ca2+ influx in sperm. In conclusion, this review highlighted the potential threat of exposure to PFASs to human spermatozoa.

BackgroundThe mortality rate associated with sepsis in elderly individuals is higher than that in younger individuals. The intestinal microbiota has been demonstrated to play an important role in the occurrence and development of sepsis. The purpose of this study was to investigate the differences in the intestinal microbiota between aged and adult mice with sepsis.MethodsThirty male C57BL mice were randomly divided into two groups: 15 in the adult group (AD group) and 15 in the age group (Age group). All the mice underwent caecal ligation and puncture to induce sepsis. Mice faeces were collected, and analysed using 16S rRNA sequencing. The liver and colon tissues were collected.ResultsThere were significant differences in intestinal microbiota composition between the two groups. Compared with adult sepsis mice, the diversity of intestinal microbiota in the aged group was significantly reduced and the structure of dominant intestinal microbiota was changed. In the Age group, the microbiota associated with inflammatory factors increased, and the microbiota associated with the production of SCFAs (Ruminiclostridium, Prevotellaceae_UCG-001, Rikenella, Parabacteroides, Oscillibacter, Odoribacter, Muribaculum, Lachnoclostridium, Intestinimonas, Faecalibaculum, Anaerotruncus, Alloprevotella and Absiella) decreased. The metabolic pathways related to the microbiota also changed. Moreover, the proportion of inflammatory factors in Age group was higher than that in AD group.ConclusionOur results showed that there were significant differences in the abundance and structure of microbiota between aged and adult sepsis mice, Aged sepsis mice have more severe intestinal microbiota destruction and liver tissue inflammation than adult sepsis mice.

The usage of expressed somatic mutations may have a unique advantage in identifying active cancer driver mutations. However, accurately calling mutations from RNA-seq data is difficult due to confounding factors such as RNA-editing, reverse transcription, and gap alignment. In the present study, we proposed a framework (named RNA-SSNV, https://github.com/pmglab/RNA-SSNV) to call somatic single nucleotide variants (SSNV) from tumor bulk RNA-seq data. Based on a comprehensive multi-filtering strategy and a machine-learning classification model trained with comprehensively curated features, RNA-SSNV achieved the best precision–recall rate (0.880–0.884) in a testing dataset and robustly retained 0.94 AUC for the precision–recall curve in three validation adult-based TCGA (The Cancer Genome Atlas) datasets. We further showed that the somatic mutations called by RNA-SSNV tended to have a higher functional impact and therapeutic power in known driver genes. Furthermore, VAF (variant allele fraction) analysis revealed that subclonal harboring expressed mutations had evolutional selection advantage and RNA had higher detection power to rescue DNA-omitted mutations. In sum, RNA-SSNV will be a useful approach to accurately call expressed somatic mutations for a more insightful analysis of cancer drive genes and carcinogenic mechanisms.

Abstract Background This study aimed to overexpress or silence connexin 43 (Cx43) and A‐kinase anchoring protein 95 (AKAP95) in human A549 cells to explore their effects on cyclins and on G1/S conversion when the interrelationship of Cx43, AKAP95, and cyclin E1/E2 changes. Methods The study mainly used Western blot analysis and Co‐immuno precipitation to detect the target protein in Cx43/AKAP95 over expressed human A549 cells, and the relationship of proteins Cx43, AKAP95 and Cyclin E during G1‐S phase was explored with qualitative and quantitative analysis. Results The overexpression of Cx43 inhibited the expression of cyclin D1 and E1 by accelerating their degradation and reduced the Cdk2 activity that blocked the DNA transcription activity. However, the overexpression of AKAP95 increased the expression of cyclin D1 and E1 and inhibited their degradation, and enhanced the Cdk2 activity that promoted the DNA transcription activity. Cx43 and AKAP95 competitively bound to cyclin E1/E2, and the competitive binding affected the Cdk2 activity, Rb phosphorylation, DNA transcription activity, and G1/S conversion. Conclusions This study showed that the expression of ERK1/2, PKA, and PKB increased when BEAS‐2B cells were treated with PDGF‐BB, suggesting that ERK1/2, PKA, and PKB might be involved in the binding of AKAP95 with cyclin E, or the separation of AKAP95 from Cx43 from cyclin E1/E2. The specific mechanism underlying this process still needs further exploration.

With the advancement of technology, medical imaging technology has been greatly improved. This article mainly studies the nursing before and after coronary angiography in cardiovascular medicine based on medical imaging technology. This paper proposes a multimodal medical image fusion algorithm based on multiscale decomposition and convolution sparse representation. The algorithm first decomposes the preregistered source medical image by NSST, takes the subimages of different scales as training images, and optimizes the subdictionaries of different scales; then convolution and sparse the subimages on each scale encoding to obtain the sparse coefficients of different subimages; secondly, the combination of improved L1 norm and improved spatial frequency (novel sum-modified SF (NMSF)) is used for high-frequency subimage coefficients, and the fusion of low-frequency subimages improved the rule of combining the L1 norm and the regional energy; finally, the final fused image is obtained by inverse NSST of the fused low-frequency subband and high-frequency subband. Experimental analysis found that the bifurcation angle has nothing to do with the damage of the branch vessels after the main branch stent is placed. The bifurcation angle greater than 50° is an independent predictor of MACE after stent extrusion for bifurcation lesions. Experimental results show that the proposed method has good performance in contrast enhancement, detail extraction, and information retention, and it improves the quality of the fusion image.

Urban fringe areas are locations that compete between urban development and ecological protection; their ecological spatial boundaries face the risk of erosion and degradation. Previous studies have so far focused on the core area inside the ecological space. However, research on the ecological boundary zone has so far been insufficient. The delineation of ECR is based on large-scale administrative units, while it is less precise at the level of small-scale rural areas. This study selected Paifang village in Nanjing City as the study area and built a Bayesian network model to predict the ecological space boundary for 2030. The study also identified the driving factors and their mechanisms affecting the changes in the rural ecological space in an urban fringe area and put forward targeted suggestions for its protection. The results suggested that: (1) The ecological space of Paifang village will expand in 2030. Specifically, agricultural land has the greatest potential for restoration of ecological space, followed by shrubland and grassland, and water bodies and their surrounding areas are potentially shrinking ecological space. (2) Artificial construction activities will disturb the ecological space, with the change in agricultural land being the main factor affecting the change in the ecological space boundary. (3) The Ecological Conservation Redline has a significant effect on the protection of the rural ecological space. The results of this study can provide a reference for rural planning and the formulation of protection policies in urban fringe areas.

Organic acids and soluble sugars are the major determinants of fruit organoleptic quality. Additionally, DNA methylation has crucial regulatory effects on various processes. However, the epigenetic modifications in the regulation of organic acid and soluble sugar accumulation in apple fruits remain uncharacterized. In this study, DNA methylation and the transcriptome were compared between ‘Honeycrisp’ and ‘Qinguan’ mature fruits, which differ significantly regarding soluble sugar and organic acid contents. In both ‘Honeycrisp’ and ‘Qinguan’ mature fruits, the CG context had the highest level of DNA methylation, and then CHG and CHH contexts. The number and distribution of differentially methylated regions (DMRs) varied among genic regions and transposable elements. The DNA methylation levels in all three contexts in the DMRs were significantly higher in ‘Honeycrisp’ mature fruits than in ‘Qinguan’ mature fruits. A combined methylation and transcriptome analysis revealed a negative correlation between methylation levels and gene expression in DMRs in promoters and gene bodies in the CG and CHG contexts and in gene bodies in the CHH context. Two candidate genes (MdTSTa and MdMa11), which encode tonoplast-localized proteins, potentially associated with fruit soluble sugar contents and acidity were identified based on expression and DNA methylation levels. Overexpression of MdTSTa in tomato increased the fruit soluble sugar content. Moreover, transient expression of MdMa11 in tobacco leaves significantly decreased the pH value. Our results reflect the diversity in epigenetic modifications influencing gene expression and will facilitate further elucidating the complex mechanism underlying fruit soluble sugar and organic acid accumulation.

Body weight (BW) is one of the most important economic traits for animal production and breeding, and it has been studied extensively for its phenotype–genotype associations. While mapping studies have mostly aimed at finding as many loci as possible that contributed to the variation in BW, the role of other factors in its genetic architecture, including their frequencies in the population and their interactions, have been largely overlooked. To comprehensively characterized the genetic architecture of BW, we performed a genome-wide association study (GWAS) both at the single-marker and haplotype level on birds from four indigenous Chinese chicken breeds (Chahua, Silkie, Langshan, and Beard), rather than studying crosses between two founder lines. Additionally, samples from two more breeds (Red Junglefowl and Recessive White) were included to better reflect variable genetic characteristics across populations. Six loci were mapped in this study, revealing the polygenic basis underlying BW. Moreover, by further examining the frequencies of the significantly associated haplotypes in each subpopulation and their effect sizes, most of the loci were found to affect BW in the Beard chicken breed alone. Two loci in GGA9 and GGA27, however, had a common effect on BW across subpopulations, showing that different underlying genetic mechanisms contribute to the phenotypic variability. These findings, particularly the variable genetic architectures found in different loci, improve our understanding of the overall genetic contributions to the large variability in BW among Chinese indigenous chicken breeds. These findings thus will have important implications for future chicken breeding.

Soluble sugars and organic acids are the main determinants of fruit organoleptic quality. To investigate the genes responsible for the soluble sugar and organic acid contents of apple fruits, a label-free proteomic analysis involving liquid chromatography (LC)-mass spectrometry (MS)/MS was conducted with the fruits of two Malus species, M. sargentii and M. niedzwetzkyana, which exhibit significant differences in soluble sugar and organic acid contents. A total of 13,036 unique peptides and 1,079 differentially-expressed proteins were identified. To verify the LC-MS/MS results, five candidate proteins were further analyzed by parallel reaction monitoring. The results were consistent with the LC-MS/MS data, which confirmed the reliability of the LC-MS/MS analysis. The functional annotation of the differentially-expressed proteins, based on the gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, revealed that they were mainly related to biological processes and cellular components. Additionally, the main enriched KEGG pathways were related to metabolic processes. Moreover, 31 proteins involved in soluble sugar metabolism, organic acid metabolism, and H+-transport were identified. The results of this study may be useful for the comprehensive characterization of the complex mechanism regulating apple fruit-soluble sugar and organic acid contents.

Significant variation in organic acid components was detected in mature fruits of 101 apple accessions using high-performance liquid chromatography. The Malus species predominantly accumulated malic acid and citric acid, whereas wild fruits exhibited significantly higher levels of organic acid content than that in cultivated fruits. Differential accumulation patterns during fruit developmental stages was detected between malic acid and citric acid, thus suggesting a complex genetic regulation mechanism of organic acid metabolism in apple fruit. A highly positive correlation was detected between fruit total organic acid content with malic acid and citric acid content, thus suggesting that malic acid and citric acid are the principal determinants of apple fruit acidity. In contrast to malic acid, citric acid was predominantly detected in partial wild apples, while extremely low to undetectable concentrations of citric acid were observed in cultivated apple fruits; this is likely due to the genetic effects of parental characters. Our results provide vital information that could be useful for future studies on genetic analysis and improvement of organic acid accumulation in apple fruits.

Context • Diabetic nephropathy (DN) is a common microvascular complication in diabetic patients. The pathogenesis of DN is complex. Inflammatory response may play a key role as a common downstream pathway. Objective • The study intended to explore the relationship between the levels of plasma nucleotide-binding oligomeric domain-like receptor protein 3 (NLRP3 inflammasome), interleukin-1β (IL-1β), and IL-18 and the progression of type 2 diabetic nephropathy to clarify their relationship with type 2 diabetes mellitus (T2DM) and to provide evidence for clinical treatment. Design • The research team performed a controlled observational study. Setting • The study took place at Baoding No. 1 Central Hospital in Baoding, Hebei, China. Participants • Participants were 153 patients with T2DM who received treatment at the hospital between October 2020 and October 2021. The research team allocated 30 participants without evidence of DN to the control group. Based on the DN stage, the team assigned the 123 remaining participants to one of five observation groups: (1) 32 participants with stage 1 DN to the DN1 group, (2) 31 participants with stage 2 DN to the DN2 group, (3) 30 participants with stage 3 DN to the DN3 group, (4) 30 participants with stage 4 DN to the DN4 group, and (5) 29 participants with stage 5 DN to the DN5 group. Outcome Measures • The research team measured participants’ levels of “nucleotide binding oligomeric domain-like receptor protein 3” (NLRP3), interleukin-1 beta (IL-1β), and IL-18 and used the Spearman rank correlation analysis to determine the correlation between those levels and the DN stages. Results • The levels of NLRP3, IL-1β and IL-18 in all the five observation groups were significantly higher than those in the control group (all P<.01). The levels were also significantly higher: (1) in the DN2, DN3, DN4, and DN5 groups than those in the DN1 group (all P<.01); (2) in the DN3, DN4, and DN5 groups than those in the DN2 group (all P<.01); (3) in the DN4 and DN5 groups than those in the DN3 group (all P < .01); and (4) in the DN5 groups than those in the DN4 group (all P < .01). The Spearman rank correlation analysis showed that the NLRP3, IL-1β, and IL-18 levels were significantly positively correlated with the DN stage (P=.01). Conclusions • NLRP3, IL-1β and IL-18 played an important role in the progression of T2DM, and their levels increased with the aggravation of DN. Therefore, the plasma levels of NLRP3, IL-1β and IL-18 can be useful as indicators of the occurrence and development of DN and can provide clinical guidance for the early diagnosis of DN and for the determination and adjustment of treatment plans. [ABSTRACT FROM AUTHOR]