Axial compression performances and bearing capacity prediction of self-compacting fly ash concrete filled circle steel tube columns.

To solve the problem of a large amount of fly ash accumulation and study the axial compression and bearing capacity prediction of the self-compacting fly ash concrete filled circle steel tube (SCCFST) columns, eight specimens are designed to explore the impact of concrete strength grade, internal structural measures, and additional parameters. The stress, progression of deformation, and failure mode of each specimen are observed during the loading process. The load-displacement curves, load-strain curves, characteristic load and displacement, ductility, and stiffness degradation are analyzed. The findings revealed that shear deformation occurred predominantly in the middle and upper portions of the steel tubes. Enhancing the strength of the concrete or adopting internal structural measures could increase the bearing capacity and ductility of the specimens. The peak load and ductility could be increased by up to 17.6 and 53.6%, respectively. The proposed unified calculation equation for the axial compression bearing capacity of SCCFST columns demonstrates notable reliability and precision. Furthermore, these tests offer valuable references for the engineering application of various forms of SCCFST columns, which are of significant importance in practical engineering.

SMTRI: A deep learning-based web service for predicting small molecules that target miRNA-mRNA interactions.

Mature microRNAs (miRNAs) are short, single-stranded RNAs that bind to target mRNAs and induce translational repression and gene silencing. Many miRNAs discovered in animals have been implicated in diseases and have recently been pursued as therapeutic targets. However, conventional pharmacological screening for candidate small-molecule drugs can be time-consuming and labor-intensive. Therefore, developing a computational program to assist mature miRNA-targeted drug discovery in silico is desirable. Our previous work (https://doi.org/10.1002/advs.201903451) revealed that the unique functional loops formed during Argonaute-mediated miRNA-mRNA interactions have stable structural characteristics and may serve as potential targets for small-molecule drug discovery. Developing drugs specifically targeting disease-related mature miRNAs and their target mRNAs would avoid affecting unrelated ones. Here, we present SMTRI, a convolutional neural network-based approach for efficiently predicting small molecules that target RNA secondary structural motifs formed by interactions between miRNAs and their target mRNAs. Measured on three additional testing sets, SMTRI outperformed state-of-the-art algorithms by 12.9%-30.3% in AUC and 2.0%-18.4% in accuracy. Moreover, four case studies on the published experimentally validated RNA-targeted small molecules also revealed the reliability of SMTRI.

Regulatory Networks of Coresident Subgenomes during Rapid Fiber Cell Elongation in Upland Cotton.

Cotton, an intriguing plant species shaped by polyploidization, evolution, and domestication, holds particular interest due to the complex mechanisms governing fiber traits across its two subgenomes. However, the regulatory elements or transcriptional networks between subgenomes during fiber elongation remain elusive. Here, we analyzed 1,462 cotton fiber samples to reconstruct gene expression regulatory networks influencing fiber cell elongation. Inter-subgenomic eQTLs largely dictate gene transcription, with a notable tendency for the D subgenome to regulate A subgenome eGenes. This regulation showcases synchronized homoeologous gene expression driven by colocalized eQTLs and divergent patterns that diminish genetic correlations, thus leading to preferential expression in the A and D subgenomes. Hotspot456 emerged as a key regulator of fiber initiation and elongation, and artificial selection of trans-eQTLs in hotspot456 positively regulating KCS1 has facilitated cell elongation. To elucidate the roles of trans-eQTL in improved fiber breeding, experimentation confirmed the inhibition of GhTOL9 by a specific trans-eQTL via GhWRKY28, which negatively impacts fiber elongation. We propose a model where the GhWRKY28-GhTOL9 module, through the Endosomal Sorting Complex Required for Transport pathway, regulates this process. This research significantly advances our understanding of cotton's evolutionary, domestication processes, and the intricate regulatory mechanisms underlying significant plant traits.

Natural variations in the Cis-elements of GhRPRS1 contributing to petal colour diversity in cotton.

The cotton genus comprises both diploid and allotetraploid species, and the diversity in petal colour within this genus offers valuable targets for studying orthologous gene function differentiation and evolution. However, the genetic basis for this diversity in petal colour remains largely unknown. The red petal colour primarily comes from C, G, K, and D genome species, and it is likely that the common ancestor of cotton had red petals. Here, by employing a clone mapping strategy, we mapped the red petal trait to a specific region on chromosome A07 in upland cotton. Genomic comparisons and phylogenetic analyses revealed that the red petal phenotype introgressed from G. bickii. Transcriptome analysis indicated that GhRPRS1, which encodes a glutathione S-transferase, was the causative gene for the red petal colour. Knocking out GhRPRS1 resulted in white petals and the absence of red spots, while overexpression of both genotypes of GhRPRS1 led to red petals. Further analysis suggested that GhRPRS1 played a role in transporting pelargonidin-3-O-glucoside and cyanidin-3-O-glucoside. Promoter activity analysis indicated that variations in the promoter, but not in the gene body of GhRPRS1, have led to different petal colours within the genus. Our findings provide new insights into orthologous gene evolution as well as new strategies for modifying promoters in cotton breeding.

Centrifugated lateral flow assay strips based on dual-emission carbon dots modified with europium ions for ratiometric determination and on-site discrimination of tetracyclines in environment.

Due to the serious detrimental impact on human health, antibiotic pollution particularly tetracyclines residues has become a serious problem. Herein, a multiple response fluorescent probe consisted of dual-emission carbon dots and Eu3+ (D-CDs@Eu3+) is designed for the determination and discrimination of tetracyclines (TCs). Specifically, the carboxyl and amidogen group of dual-emission carbon dots (D-CDs) can coordinate with Eu3+ to form the D-CDs@Eu3+. Upon adding TCs, the fluorescence intensities of D-CDs at 405 nm and 495 nm are quenched due to inner filter effect (IFE) and the localization of fluorescence resonance energy transfer (L-FRET) between the D-CDs@Eu3+ and TC. Simultaneously, the D-CDs@Eu3+ may chelate with TCs to enhance the occurrence of antenna effect, while the characteristic peaks of Eu3+ at 590 nm and 615 nm are enhanced. On these bases, the TCs detection is achieved with low detection limits from 46.7 to 72.0 nM. Additionally, through the distinct efficiencies of L-FRET, the discrimination of TCs is achieved. Moreover, a novel centrifugated lateral flow assay strips (CLFASs) device is developed by integrating the D-CDs@Eu3+, lateral flow assay strips and smartphone using RGB variations for TCs detection, achieving remarkable recoveries (98.6-103.7 %) in real samples. Therefore, this CLFASs device provides a reliable approach for the TCs detection, demonstrating potential applications.

Redefinition of Synovial Fibroblasts in Rheumatoid Arthritis.

The breakdown of immune tolerance and the rise in autoimmunity contribute to the onset of rheumatoid arthritis (RA), driven by significant changes in immune components. Recent advances in single-cell and spatial transcriptome profiling have revealed shifts in cell distribution and composition, expanding our understanding beyond molecular-level changes in inflammatory cytokines, autoantibodies, and autoantigens in RA. Surprisingly, synovial fibroblasts (SFs) play an active immunopathogenic role rather than remaining passive bystanders in RA, with notable alterations in their subpopulation distribution and composition. This study examines these changes in SF heterogeneity, assesses their impact on RA progression, and elucidates the immune characteristics and functions of SF subsets in the RA autoimmunity, encompassing both intrinsic and adaptive immunity. Additionally, this review discusses therapeutic strategies targeting immune SF subsets, highlighting the potential of future interventions in SF phenotypic reprogramming. Overall, this review redefines the role of SFs in RA and suggests targeting SF phenotypic reprogramming and its upstream molecules as a promising therapeutic approach to restore immune balance and modulate immune tolerance in RA.

Biological Clock Perspective in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic polyarticular pain, and its main pathological features include inflammatory cell infiltration, synovial fibroblast proliferation, and cartilage erosion. Immune cells, synovial cells and neuroendocrine factors play pivotal roles in the pathophysiological mechanism underlying rheumatoid arthritis. Biological clock genes regulate immune cell functions, which is linked to rhythmic changes in arthritis pathology. Additionally, the interaction between biological clock genes and neuroendocrine factors is also involved in rhythmic changes in rheumatoid arthritis. This review provides an overview of the contributions of circadian rhythm genes to RA pathology, including their interaction with the immune system and their involvement in regulating the secretion and function of neuroendocrine factors. A molecular understanding of the role of the circadian rhythm in RA may offer insights for effective disease management.

Sclerostin inhibition in rare bone diseases: Molecular understanding and therapeutic perspectives.

Sclerostin emerges as a novel target for bone anabolic therapy in bone diseases. Osteogenesis imperfecta (OI) and X-linked hypophosphatemia (XLH) are rare bone diseases in which therapeutic potential of sclerostin inhibition cannot be ignored. In OI, genetic/pharmacologic sclerostin inhibition promoted bone formation of mice, but responses varied by genotype and age. Serum sclerostin levels were higher in young OI-I patients, while lower in adult OI-I/III/IV. It's worth investigating whether therapeutic response of OI to sclerostin inhibition could be clinically predicted by genotype and age. In XLH, preclinical/clinical data suggested factors other than identified FGF23 contributing to XLH. Higher levels of circulating sclerostin were detected in XLH. Sclerostin inhibition promoted bone formation in Hyp mice, while restored phosphate homeostasis in age-/gender-dependent manner. The role of sclerostin in regulating phosphate metabolism deserves investigation. Sclerostin/FGF23 levels of XLH patients with/without response to FGF23-antibody warrants study to develop precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy. Notably, OI patients were associated with cardiovascular abnormalities, so were XLH patients receiving conventional therapy. Targeting sclerostin loop3 promoted bone formation without cardiovascular risks. Further, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety. The Translational Potential of this Article. Preclinical data on the molecular understanding of sclerostin inhibition in OI and therapeutic efficacy in mouse models of different genotypes, as well as clinical data on serum sclerostin levels in patients with different phenotypes of OI, were reviewed and discussed. Translationally, it would facilitate to develop clinical prediction strategies (e.g. based on genotype and age, not just phenotype) for OI patients responsive to sclerostin inhibition. Both preclinical and clinical data suggested sclerostin as another factor contributing to XLH, in addition to the identified FGF23. The molecular understanding and therapeutic effects of sclerostin inhibition on both promoting bone anabolism and improving phosphate homostasis in Hyp mice were reviewed and discussed. Translationaly, it would facilitate the development of precise sclerostin/FGF23 inhibition strategy or synergistic/additive strategy for the treatment of XLH. Cardiovascular risk could not be ruled out during sclerostin inhibition treatment, especially for OI and XLH patients with cardiovascular diseases history and cardiovascular abnormalities. Studies on the role of sclerostin in inhiting bone formation and protecting cardiovascular system were reviewed and discussed. Translationaly, blockade of sclerostin loop3-LRP4 interaction while preserving sclerostin loop2-ApoER2 interaction could be a potential precise sclerostin inhibition strategy for OI and XLH with cardiovascular safety.

Artificial Intelligence-Based Microfluidic Platform for Detecting Contaminants in Water: A Review.

Water pollution greatly impacts humans and ecosystems, so a series of policies have been enacted to control it. The first step in performing pollution control is to detect contaminants in the water. Various methods have been proposed for water quality testing, such as spectroscopy, chromatography, and electrochemical techniques. However, traditional testing methods require the utilization of laboratory equipment, which is large and not suitable for real-time testing in the field. Microfluidic devices can overcome the limitations of traditional testing instruments and have become an efficient and convenient tool for water quality analysis. At the same time, artificial intelligence is an ideal means of recognizing, classifying, and predicting data obtained from microfluidic systems. Microfluidic devices based on artificial intelligence and machine learning are being developed with great significance for the next generation of water quality monitoring systems. This review begins with a brief introduction to the algorithms involved in artificial intelligence and the materials used in the fabrication and detection techniques of microfluidic platforms. Then, the latest research development of combining the two for pollutant detection in water bodies, including heavy metals, pesticides, micro- and nanoplastics, and microalgae, is mainly introduced. Finally, the challenges encountered and the future directions of detection methods based on industrial intelligence and microfluidic chips are discussed.

Mime: A flexible machine-learning framework to construct and visualize models for clinical characteristics prediction and feature selection.

The widespread use of high-throughput sequencing technologies has revolutionized the understanding of biology and cancer heterogeneity. Recently, several machine-learning models based on transcriptional data have been developed to accurately predict patients' outcome and clinical response. However, an open-source R package covering state-of-the-art machine-learning algorithms for user-friendly access has yet to be developed. Thus, we proposed a flexible computational framework to construct a machine learning-based integration model with elegant performance (Mime). Mime streamlines the process of developing predictive models with high accuracy, leveraging complex datasets to identify critical genes associated with prognosis. An in silico combined model based on de novo PIEZO1-associated signatures constructed by Mime demonstrated high accuracy in predicting the outcomes of patients compared with other published models. Furthermore, the PIEZO1-associated signatures could also precisely infer immunotherapy response by applying different algorithms in Mime. Finally, SDC1 selected from the PIEZO1-associated signatures demonstrated high potential as a glioma target. Taken together, our package provides a user-friendly solution for constructing machine learning-based integration models and will be greatly expanded to provide valuable insights into current fields. The Mime package is available on GitHub (https://github.com/l-magnificence/Mime).

Mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.

An earlier study found that respiratory cadmium chloride (CdCl2) exposure caused COPD-like lung injury. This study aimed to explore whether mitochondrial dysfunction-mediated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury. Adult C57BL/6 mice were exposed to CdCl2 (10 mg/L) aerosol for six months. Beta-galactosidase-positive cells, p21 and p16 were increased in CdCl2-exposed mouse lungs. The in vitro experiments showed that γ-H2AX was elevated in CdCl2-exposed alveolar epithelial cells. The cGAS-STING pathway was activated in CdCl2-exposed alveolar epithelial cells and mouse lungs. Cxcl1, Cxcl9, Il-10, Il-1ß and Mmp2, several senescence-associated secretory phenotypes (SASP), were upregulated in CdCl2-exposed alveolar epithelial cells. Mechanistically, CdCl2 exposure caused SIRT3 reduction and mitochondrial dysfunction in mouse lungs and alveolar epithelial cells. The in vitro experiment found that Sirt3 overexpression attenuated CdCl2-induced alveolar epithelial senescence and SASP. The in vivo experiments showed that Sirt3 gene knockout exacerbated CdCl2-induced alveolar epithelial senescence, alveolar structure damage, airway inflammation and pulmonary function decline. NMN, an NAD+ precursor, attenuated CdCl2-induced alveolar epithelial senescence and SASP in mouse lungs. Moreover, NMN supplementation prevented CdCl2-induced COPD-like alveolar structure damage, epithelial-mesenchymal transition and pulmonary function decline. These results suggest that mitochondrial dysfunction-associated alveolar epithelial senescence is involved in CdCl2-induced COPD-like lung injury.

Exposure to 1-nitropyrene after weaning induces anxiety-like behavior partially by inhibiting steroid hormone synthesis in prefrontal cortex.

1-Nitropyrene (1-NP) is a neurodevelopmental toxicant. This study was to evaluate the impact of exposure to 1-NP after weaning on anxiety-like behavior. Five-week-old mice were administered with 1-NP (0.1 or 1 mg/kg) daily for 4 weeks. Anxiety-like behaviour was measured using elevated-plus maze (EPM) and open field test (OFT). In EPM test, time spending in open arm and times entering open arm were reduced in 1-NP-treated mice. In OFT test, time spent in the center region and times entering the center region were diminished in 1-NP-treated mice. Prefrontal dendritic length and number of dendrite branches were decreased in 1-NP-treated mice. Prefrontal PSD95, an excitatory postsynaptic membrane protein, and gephyrin, an inhibitory postsynaptic membrane protein, were downregulated in 1-NP-treated mice. Further analysis showed that peripheral steroid hormones, including serum testosterone (T) and estradiol (E2), testicular T, and ovarian E2, were decreased in 1-NP-treated mice. Interestingly, T and E2 were diminished in 1-NP-treated prefrontal cortex. Prefrontal T and E2 synthases were diminished in 1-NP-treated mice. Mechanistically, GCN2-eIF2α, a critical pathway that regulates ribosomal protein translation, was activated in 1-NP-treated prefrontal cortex. These results indicate that exposure to 1-NP after weaning induces anxiety-like behaviour partially by inhibiting steroid hormone synthesis in prefrontal cortex.

Enrichment of Trypsin Inhibitor from Soybean Whey Wastewater Using Different Precipitating Agents and Analysis of Their Properties.

Recovering valuable active substances from the by-products of agricultural processing is a crucial concern for scientific researchers. This paper focuses on the enrichment of soybean trypsin inhibitor (STI) from soybean whey wastewater using either ammonium sulfate salting or ethanol precipitation, and discusses their physicochemical properties. The results show that at a 60% ethanol content, the yield of STI was 3.983 mg/mL, whereas the yield was 3.833 mg/mL at 60% ammonium sulfate saturation. The inhibitory activity of STI obtained by ammonium sulfate salting out (A-STI) was higher than that obtained by ethanol precipitation (E-STI). A-STI exhibited better solubility than E-STI at specific temperatures and pH levels, as confirmed by turbidity and surface hydrophobicity measurements. Thermal characterization revealed that both A-STI and E-STI showed thermal transition temperatures above 90 °C. Scanning electron microscopy demonstrated that A-STI had a smooth surface with fewer pores, while E-STI had a rough surface with more pores. In conclusion, there was no significant difference in the yield of A-STI and E-STI (p < 0.05); however, the physicochemical properties of A-STI were superior to those of E-STI, making it more suitable for further processing and utilization. This study provides a theoretical reference for the enrichment of STI from soybean whey wastewater.

Using a combination of δ13CDIC-DOC-difference in dissolved inorganic and organic carbon, δ2H, and δ18O to localize leachate leaks at landfill sites in China.

The investigation of leachate leakage at numerous landfill sites is urgently needed. This study presents an exploration of environmental tracing methods using δ2H and δ13C-difference in dissolved carbon (δ13CDIC-DOC) to localize leachate leak points at landfill sites. δ2H, δ13CDIC, δ13CDOC, δ18O, and an array of physicochemical indices (e.g., total dissolved solids, temperature, and oxidation reduction potential) were monitored in both leachate and groundwater from different zones of a landfill site in China during the year of 2021-2023. Moreover, data for these parameters (i.e., the isotopic composition and physicochemical indices) from twelve published landfill cases were also collected, and these groundwater/leachate data points were located within 1 km away from the landfill boundary. Then statistical analyses, such as Pearson correlation analysis and redundancy analysis (RDA), were performed using both the detected and collected parameters at landfill sites. Consequently, the intensity of interaction between leachate and background groundwater was found to significantly control the isotopic fractionation features of hydrogen and carbon, and both the content of major contamination indicators (total dissolved solids, chemical oxygen demand, and ammoniacal nitrogen) and the oxidation reduction potential were the key impact factors. Accordingly, the water type used to indicate leachate leakage points was determined to be leachate that significantly interacted with the background groundwater or precipitation (LBGP). δ2H showed a perfect linear correlation (0.81 ≤ r2 < 1.0) with δ13CDIC-DOC in leachate under highly anaerobic landfill conditions, and the δ2H & δ13CDIC-DOC combinations in the LBGP were significantly different from those in the other water types. For groundwater with total dissolved solids lower than 1400 mg/L at landfill sites, a strong positive linear correlation (r = 0.83) was revealed between δ13CDIC and δ13CDOC. Based on these insights, δ2H versus δ13CDIC-DOC plots and RDA using δ2H and δ13CDIC-DOC as response variables were proposed to localize leak points at both lined landfills and leachate facilities. These findings further understanding of the isotopic fractionation features of hydrogen, carbon, and oxygen and provide novel environmental tracer methods for investigating leachate leak points at MSW landfill sites.

Polystyrene nanoplastics distinctly impact cadmium uptake and toxicity in Arabidopsis thaliana.

The ubiquitous presence of micro- and nanoplastics (MNPs) in soil has raised concerns regarding their potential effects on terrestrial plants. The coexistence and interactions between MNPs and heavy metals altering their phytotoxicity deserves further investigation. In this study, we explored the impacts of various concentrations of polystyrene nanoplastics (PS-NPs) and cadmium (Cd) alone or in combination on the growth and development of Arabidopsis thaliana. Additionally, we examined the effects of combined stress on the uptake and translocation of Cd within Arabidopsis thaliana. Our findings revealed several key insights: PS-NPs exhibited the capability to internalize in the maturation zone of Arabidopsis roots; the presence of Cd changed the particle size and zeta potential of PS-NPs; the presence of PS-NPs heightened Cd accumulation in the underground parts of Arabidopsis seedlings, leading to a stronger oxidative stress response in these regions; the composite stress exerted a more pronounced effect on the growth and development of Arabidopsis compared to individual stresses. Interestingly, while higher PS-NPs concentrations hindered Cd migration from roots to leaves, they also acted as carriers for Cd uptake in Arabidopsis roots. These findings shed light on the combined impacts of MNPs and heavy metals on plant physiology, offering theoretical insights to guide risk assessment strategies for MNPs and heavy metals in terrestrial ecosystems.

Mitochondrial GPX4 acetylation is involved in cadmium-induced renal cell ferroptosis.

Increasing evidences demonstrate that environmental stressors are important inducers of acute kidney injury (AKI). This study aimed to investigate the impact of exposure to Cd, an environmental stressor, on renal cell ferroptosis. Transcriptomics analyses showed that arachidonic acid (ARA) metabolic pathway was disrupted in Cd-exposed mouse kidneys. Targeted metabolomics showed that renal oxidized ARA metabolites were increased in Cd-exposed mice. Renal 4-HNE, MDA, and ACSL4, were upregulated in Cd-exposed mouse kidneys. Consistent with animal experiments, the in vitro experiments showed that mitochondrial oxidized lipids were elevated in Cd-exposed HK-2 cells. Ultrastructure showed mitochondrial membrane rupture in Cd-exposed mouse kidneys. Mitochondrial cristae were accordingly reduced in Cd-exposed mouse kidneys. Mitochondrial SIRT3, an NAD+-dependent deacetylase that regulates mitochondrial protein stability, was reduced in Cd-exposed mouse kidneys. Subsequently, mitochondrial GPX4 acetylation was elevated and mitochondrial GPX4 protein was reduced in Cd-exposed mouse kidneys. Interestingly, Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3-/- mice. Conversely, Cd-induced mitochondrial oxidized lipids were attenuated in nicotinamide mononucleotide (NMN)-pretreated HK-2 cells. Moreover, Cd-evoked mitochondrial GPX4 acetylation and renal cell ferroptosis were alleviated in NMN-pretreated mouse kidneys. These results suggest that mitochondrial GPX4 acetylation, probably caused by SIRT3 downregulation, is involved in Cd-evoked renal cell ferroptosis.

Prenatal 1-Nitropyrene Exposure Causes Autism-Like Behavior Partially by Altering DNA Hydroxymethylation in Developing Brain.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, characterized by social communication disability and stereotypic behavior. This study aims to investigate the impact of prenatal exposure to 1-nitropyrene (1-NP), a key component of motor vehicle exhaust, on autism-like behaviors in a mouse model. Three-chamber test finds that prenatal 1-NP exposure causes autism-like behaviors during the weaning period. Patch clamp shows that inhibitory synaptic transmission is reduced in medial prefrontal cortex of 1-NP-exposed weaning pups. Immunofluorescence finds that prenatal 1-NP exposure reduces the number of prefrontal glutamate decarboxylase 67 (GAD67) positive interneurons in fetuses and weaning pups. Moreover, prenatal 1-NP exposure retards tangential migration of GAD67-positive interneurons and downregulates interneuron migration-related genes, such as Nrg1, Erbb4, and Sema3F, in fetal forebrain. Mechanistically, prenatal 1-NP exposure reduces hydroxymethylation of interneuron migration-related genes through inhibiting ten-eleven translocation (TET) activity in fetal forebrain. Supplement with alpha-ketoglutarate (α-KG), a cofactor of TET enzyme, reverses 1-NP-induced hypohydroxymethylation at specific sites of interneuron migration-related genes. Moreover, α-KG supplement alleviates 1-NP-induced migration retardation of interneurons in fetal forebrain. Finally, maternal α-KG supplement improves 1-NP-induced autism-like behaviors in weaning offspring. In conclusion, prenatal 1-NP exposure causes autism-like behavior partially by altering DNA hydroxymethylation of interneuron migration-related genes in developing brain.

Comparative chloroplast-specific SNP and nSCoT markers analysis and population structure study in kiwifruit plants.

BACKGROUND: Kiwifruit (Actinidiaceae family) is an economically important fruit tree in China and New Zealand. It is a typical dioecious plant that has undergone frequent natural hybridization, along with chromosomal ploidy diversity within the genus Actinidia, resulting in higher genetic differences and horticultural diversity between interspecific and intraspecific traits. This diversity provides a rich genetic base for breeding. China is not only the original center of speciation for the Actinidia genus but also its distribution center, housing the most domesticated species: A. chinensis var. chinensis, A. chinensis var. deliciosa, A. arguta, and A. polygama. However, there have been relatively few studies on the application of DNA markers and the genetic basis of kiwifruit plants. By combining information from chloroplast-specific SNPs and nuclear SCoT (nSCoT) markers, we can uncover complementary aspects of genetic variation, population structure, and evolutionary relationships. In this study, one chloroplast DNA (cpDNA) marker pair was selected out of nine cpDNA candidate pairs. Twenty nSCoT markers were selected and used to assess the population structure and chloroplast-specific DNA haplotype diversity in 55 kiwifruit plants (Actinidia), including 20 samples of A. chinensis var. chinensis, 22 samples of A. chinensis var. deliciosa, 11 samples of A. arguta, and two samples of A. polygama, based on morphological observations collected from China. RESULTS: The average genetic distance among the 55 samples was 0.26 with chloroplast-specific SNP markers and 0.57 with nSCoT markers. The Mantel test revealed a very small correlation (r = 0.21). The 55 samples were categorized into different sub-populations using Bayesian analysis, the Unweighted Pair Group Method with the Arithmetic Mean (UPGMA), and the Principal Component Analysis (PCA) method, respectively. Based on the analysis of 205 variable sites, a total of 15 chloroplast-specific DNA haplotypes were observed, contributing to a higher level of polymorphism with an Hd of 0.78. Most of the chloroplast-specific DNA haplotype diversity was distributed among populations, but significant diversity was also observed within populations. H1 was shared by 24 samples, including 12 of A. chinensis var. chinensis and 12 of A. chinensis var. deliciosa, indicating that H1 is an ancient and dominant haplotype among the 55 chloroplast-specific sequences. H2 may not have evolved further.The remaining haplotypes were rare and unique, with some appearing to be exclusive to a particular variety and often detected in single individuals. For example, the H15 haplotype was found exclusively in A. polygama. CONCLUSION: The population genetic variation explained by chloroplast-specific SNP markers has greater power than that explained by nSCoTs, with chloroplast-specific DNA haplotypes being the most efficient. Gene flow appears to be more evident between A. chinensis var. chinensis and A. chinensis var. deliciosa, as they share chloroplast-specific DNA haplotypes, In contrast, A.arguta and A. polygama possess their own characteristic haplotypes, derived from the haplotype of A. chinensis var. chinensis. Compared with A. chinensis, the A.arguta and A. polygama showed better grouping. It also seems crucial to screen out, for each type of molecular marker, especially haplotypes, the core markers of the Actinidia genus.

Arsenic exposure causes decline in sperm motility accompanied by energy metabolism disorders in mouse testes.

Arsenic (As) is a notorious environmental toxicant widely present in various natural environments. As exposure has been correlated with the decline in sperm motility. Yet, the mechanism has not been fully elucidated. Adult male C57 mice were given 0, 1, or 15 mg/L NaAsO2 for 10 weeks. The mature seminiferous tubules and sperm count were decreased in As-exposed mice. Sperm motility and several sperm motility parameters, including average path velocity (VAP), straight-line velocity (VSL), curvilinear velocity (VCL), beat-cross frequency (BCF), linearity (LIN), straightness (STR), and amplitude of lateral head displacement (ALH), were declined in As-exposed mice. RNA sequencing and transcriptomics analyses revealed that differentially expressed genes (DEGs) were mainly enriched in metabolic pathways. Untargeted metabolomics analyses indicated that energy metabolism was disrupted in As-exposed mouse testes. Gene set enrichment analysis showed that glycolysis and oxidative phosphorylation were disturbed in As-exposed mouse testes. As-induced disruption of testicular glucose metabolism and oxidative phosphorylation was further validated by RT-PCR and Western blotting. In conclusion, As exposure causes decline in sperm motility accompanied by energy metabolism disorders in mouse testes.

A potassium-chloride co-transporter with altered genome architecture functions as a suppressor in glioma.

Gliomas, the most lethal tumours in brain, have a poor prognosis despite accepting standard treatment. Limited benefits from current therapies can be attributed to genetic, epigenetic and microenvironmental cues that affect cell programming and drive tumour heterogeneity. Through the analysis of Hi-C data, we identified a potassium-chloride co-transporter SLC12A5 associated with disrupted topologically associating domain which was downregulated in tumour tissues. Multiple independent glioma cohorts were included to analyse the characterization of SLC12A5 and found it was significantly associated with pathological features, prognostic value, genomic alterations, transcriptional landscape and drug response. We constructed two SLC12A5 overexpression cell lines to verify the function of SLC12A5 that suppressed tumour cell proliferation and migration in vitro. In addition, SLC12A5 was also positively associated with GABAA receptor activity and negatively associated with pro-tumour immune signatures and immunotherapy response. Collectively, our study provides a comprehensive characterization of SLC12A5 in glioma and supports SLC12A5 as a potential suppressor of disease progression.