The relationship of immune cells with autism spectrum disorder: a bidirectional Mendelian randomization study.

BACKGROUND: Observational studies have indicated a correlation between immunological inflammation and the risk of autism spectrum disorder (ASD). However, the causal relationship between immunological inflammation and ASD remains uncertain. METHODS: Immunity-wide data sources were retrieved from the GWAS catalog. Genetic summary data on ASD were retrieved from two independent GWAS. We performed two independent bi-directional, two-sample Mendelian randomization (MR) analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between ASD and immune cell signatures. RESULTS: We have discovered 26 potential correlations between genetic predisposition in the immunophenotypes and ASD. The meta-analysis of the two inverse variance weighted (IVW)-produced estimates provided further evidence supporting the potential causal relationship between immunophenotypes and ASD. Based on the findings of the reverse MR analysis, it was determined that there are two potential negative causal relationships between ASD and immunophenotypes. However, the meta-analysis of the two IVW-derived MR estimates indicated that immunophenotypes were not significantly influenced by ASD (OR = 0.87, 95% CI = 0.73 -1.03, P = 0.09; OR = 0.91, 95% CI = 0.81-1.01, P = 0.08). CONCLUSIONS: This study expanded immune cell subtypes that were potentially causally associated with ASD risk as well as identified ASD-specific immune cell subtypes. The discovery has the potential to lead to earlier detection and more effective treatment techniques.

Distribution and relationship of antibiotics, heavy metals and resistance genes in the upstream of Hanjiang River Basin in Shiyan, China.

The upstream basin of Hanjiang River is an important water source for the middle route of China's South-to-North Water Diversion Project. The quality of water and soil in the Hanjiang River have enormous biological and environmental impacts, and resistant genetic contamination has emerged, but only few studies are concerned the correlation between heavy metals and metal resistance genes (MRGs). In this study, 8 antibiotics and 19 heavy metals were analyzed, the results showed that the highest antibiotic content was tetracycline, with mean concentrations of 43.201 µg/kg and 0.022 µg/L. Mn was the highest heavy metal in soil with a content of 1408.284 µg/kg, and in water was Zn with a content of 10.611 µg/L. We found that the most abundant antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) in the study area were bacA and arsT genes, coding for resistance mechanisms to bacitracin and arsenic, respectively. The data showed that heavy metals had a greater impact on antibiotic resistance genes than antibiotics, and the correlation between resistance genes was significantly positive. This work expands our understanding of the correlations of antibiotics, heavy metals, and resistance genes in the Hanjiang River, indicating that more attention should be paid to the effects of resistance genes and the quality of water.

Association between gut microbiota and postpartum depression: A bidirectional Mendelian randomization study.

BACKGROUNDS: Empirical investigations have shown an association between gut microbiota and postpartum depression (PPD); nevertheless, the precise cause-and-effect relationship between these two variables remains ambiguous. This research aimed to examine the possible reciprocal causal relationship between the gut microbiota and PPD. METHODS: In this work, we used Mendelian randomization (MR) to analyze the relationship between the gut microbiota (n = 18,340) and PPD (n = 67,205). We obtained the relevant SNPs from publicly accessible genome-wide association studies (GWAS). The SNP estimations were combined by the inverse-variance weighted (IVW) method, including sensitivity analyses such as weighted median, MR Egger, and MR Pleiotropy Residual Sum and Outlier (PRESSO). RESULTS: We have identified strong correlations between six bacterial characteristics and the likelihood of developing PPD. Our research revealed that the genus Ruminococcaceae UCG010, the family Veillonellaceae, and the class Clostridia had a beneficial effect on preventing PPD. The class Alphaproteobacteria, genus Slackia, and order NB1n were found to have a significant negative impact on PPD. The sensitivity studies conducted on these bacterial features consistently confirmed these finding. LIMITATIONS: It is crucial to acknowledge that our study was conducted just within a European society, which may restrict its applicability to other groups. CONCLUSIONS: The findings from our MR investigation indicate a potential causal relationship between certain kinds of gut bacteria and PPD. Additional investigation is required to elucidate the influence of gut microbiota on the advancement of PPD.

Progressive meristem and single-cell transcriptomes reveal the regulatory mechanisms underlying maize inflorescence development and sex differentiation.

Maize develops separate ear and tassel inflorescences with initially similar morphology but ultimately different architecture and sexuality. The detailed regulatory mechanisms underlying these changes still remain largely unclear. In this study, through analyzing the time-course meristem transcriptomes and floret single-cell transcriptomes of ear and tassel, we revealed the regulatory dynamics and pathways underlying inflorescence development and sex differentiation. We identified 16 diverse gene clusters with differential spatiotemporal expression patterns and revealed biased regulation of redox, programmed cell death, and hormone signals during meristem differentiation between ear and tassel. Notably, based on their dynamic expression patterns, we revealed the roles of two RNA-binding proteins in regulating inflorescence meristem activity and axillary meristem formation. Moreover, using the transcriptional profiles of 53 910 single cells, we uncovered the cellular heterogeneity between ear and tassel florets. We found that multiple signals associated with either enhanced cell death or reduced growth are responsible for tassel pistil suppression, while part of the gibberellic acid signal may act non-cell-autonomously to regulate ear stamen arrest during sex differentiation. We further showed that the pistil-protection gene SILKLESS 1 (SK1) functions antagonistically to the known pistil-suppression genes through regulating common molecular pathways, and constructed a regulatory network for pistil-fate determination. Collectively, our study provides a deep understanding of the regulatory mechanisms underlying inflorescence development and sex differentiation in maize, laying the foundation for identifying new regulators and pathways for maize hybrid breeding and improvement.

Polystyrene microplastics enhance oxidative dissolution but suppress the aquatic acute toxicity of a commercial cadmium yellow pigment under simulated irradiation.

Commercial cadmium yellow (CdS) pigment widely coexist with microplastics (MPs) in surface water, thus it is important to understand how MPs affect CdS pigment stability and toxicity under irradiation. Herein, the dissolution of CdS pigment (krelease = 0.118 h-1) under irradiation was visibly increased to 0.144 h-1 by polystyrene (PS) MPs, due to reactive species generation such as 1O2, •OH and 3PS* , while O2•- was unimportant to this process. The O2, humic acid, photoaging status of PS MPs could promote PS MPs-related CdS pigment dissolution rate by modifying reactive species generation. However, the CO32-, PO43- and alkaline condition significantly decreased the dissolution rate to 0.091, 0.053 and 0.094 h-1, respectively, through modifying free Cd2+ stability. Comparably, PS MPs-related CdS pigment dissolution was relatively slow in natural water samples (krelease = 0.075 h-1). PS MPs at environmental concentration can also promote CdS pigment dissolution and Cd2+ release, but suppress acute toxicity of CdS pigment to zebrafish larvae as increasing 10 h survival from 65% to 85% by adsorbing the Cd2+ and decreasing Cd2+ bioavailability. This study emphasized the environmental risks and human safety of CdS pigment should be carefully evaluated in the presence of PS MPs in aquatic environments.

Review and prospect of immune checkpoint blockade therapy represented by PD-1/PD-L1 in the treatment of clear cell renal cell carcinoma.

As a common tumor of the urinary system, the morbidity and mortality related to renal carcinoma, are increasing annually. Clear cell renal cell carcinoma (CCRCC) is the most common subtype of renal cell carcinoma, accounting for approximately 75% of the total number of patients with renal cell carcinoma. Currently, the clinical treatment of ccRCC involves targeted therapy, immunotherapy, and a combination of the two. In immunotherapy, PD-1/PD-L1 blocking of activated T cells to kill cancer cells is the most common treatment. However, as treatment progresses, some patients gradually develop resistance to immunotherapy. Meanwhile, other patients experience great side effects after immunotherapy, resulting in a survival status far lower than the expected survival rate. Based on these clinical problems, many researchers have been working on the improvement of tumor immunotherapy in recent years and have accumulated numerous research results. We hope to find a more suitable direction for future immunotherapy for ccRCC by combining these results and the latest research progress.

A multi-omics integrative network map of maize.

Networks are powerful tools to uncover functional roles of genes in phenotypic variation at a system-wide scale. Here, we constructed a maize network map that contains the genomic, transcriptomic, translatomic and proteomic networks across maize development. This map comprises over 2.8 million edges in more than 1,400 functional subnetworks, demonstrating an extensive network divergence of duplicated genes. We applied this map to identify factors regulating flowering time and identified 2,651 genes enriched in eight subnetworks. We validated the functions of 20 genes, including 18 with previously unknown connections to flowering time in maize. Furthermore, we uncovered a flowering pathway involving histone modification. The multi-omics integrative network map illustrates the principles of how molecular networks connect different types of genes and potential pathways to map a genome-wide functional landscape in maize, which should be applicable in a wide range of species.

Development of a Novel Sphingolipid Signaling Pathway-Related Risk Assessment Model to Predict Prognosis in Kidney Renal Clear Cell Carcinoma.

This study aimed to explore underlying mechanisms by which sphingolipid-related genes play a role in kidney renal clear cell carcinoma (KIRC) and construct a new prognosis-related risk model. We used a variety of bioinformatics methods and databases to complete our exploration. Based on the TCGA database, we used multiple R-based extension packages for data transformation, processing, and statistical analyses. First, on analyzing the CNV, SNV, and mRNA expression of 29 sphingolipid-related genes in various types of cancers, we found that the vast majority were protective in KIRC. Subsequently, we performed cluster analysis of patients with KIRC using sphingolipid-related genes and successfully classified them into the following three clusters with significant prognostic differences: Cluster 1, Cluster 2, and Cluster 3. We performed differential analyses of transcription factor activity, drug sensitivity, immune cell infiltration, and classical oncogenes to elucidate the unique roles of sphingolipid-related genes in cancer, especially KIRC, and provide a reference for clinical treatment. After analyzing the risk rates of sphingolipid-related genes in KIRC, we successfully established a risk model composed of seven genes using LASSO regression analysis, including SPHK1, CERS5, PLPP1, SGMS1, SGMS2, SERINC1, and KDSR. Previous studies have suggested that these genes play important biological roles in sphingolipid metabolism. ROC curve analysis results showed that the risk model provided good prediction accuracy. Based on this risk model, we successfully classified patients with KIRC into high- and low-risk groups with significant prognostic differences. In addition, we performed correlation analyses combined with clinicopathological data and found a significant correlation between the risk model and patient's M, T, stage, grade, and fustat. Finally, we developed a nomogram that predicted the 5-, 7-, and 10-year survival in patients with KIRC. The model we constructed had strong predictive ability. In conclusion, we believe that this study provides valuable data and clues for future studies on sphingolipid-related genes in KIRC.

Polystyrene microplastics protect lettuce (Lactuca sativa) from the hazardous effects of Cu(OH)2 nanopesticides.

Copper-based nanopesticides are released into the environment during foliar spray application, and they could, on their own or in combination with microplastics (MPs), pose threats to environmental safety and human health. In this study, Cu(OH)2 nanowires greatly decreased the vigor of lettuce seeds (p< 0.01) and the root length of lettuce seedlings (p< 0.01) and significantly altered the lettuce antioxidant defence system and MDA content (p< 0.05). Released Cu2+ played a critical role in the toxicity mechanism of Cu(OH)2 nanowires in lettuce seedlings, as evidenced by the substantial accumulation of Cu in the seedling roots (p< 0.01) rather than in the leaves. Polystyrene (PS) MPs (1 mg/L) stimulated lettuce seedling growth, as shown by the (highly) significant increase in root and leaf length and in the seed vigor index (p< 0.01 or 0.05). Notably, PS MPs (1 mg/L) neutralized the hazardous effects of 1 mg/L Cu(OH)2 nanowire treatment on lettuce growth, as reflected by the vitality and root length of the seedlings returning to normal levels. The PS MPs (1 mg/L) absorbed on middle root surfaces and strongly hindered Cu accumulation in lettuce roots, which was the predominant mechanism by which PS MPs suppressed the hazardous effects of the Cu(OH)2 nanowires. This study strengthens the understanding of the toxicity and toxicity mechanisms of Cu(OH)2 nanowires with or without PS MPs in the environment.

Lipid metabolism in ferroptosis and ferroptosis-based cancer therapy.

Ferroptosis refers to iron-dependent, specialized, and regulated-necrosis mediated by lipid peroxidation, which is closely related to a variety of diseases, including cancer. Tumor cells undergo extensive changes in lipid metabolism, including lipid peroxidation and ferroptosis. Changes in lipid metabolism are critical for the regulation of ferroptosis and thus have important roles in cancer therapy. In this review, we introduce the characteristics of ferroptosis and briefly analyze the links between several metabolic mechanisms and ferroptosis. The effects of lipid peroxides, several signaling pathways, and the molecules and pathways involved in lipid metabolism on ferroptosis were extensively analyzed. Finally, our review highlights some ferroptosis-based treatments and presents some methods and examples of how these treatments can be combined with other treatments.

Glassy or Amorphous? A Demonstration Using G-Phase Copper Containing a Fivefold Twinning Structure.

The G-phase, a new metastable phase with its potential energy sitting right in the middle of the glass and crystal, was recently discovered in some simulations when the molten metallic liquid was quenched down to room temperature. In comparison with ordinary glass, the G-phase has a more ordered short-range structure but a similarly disordered long-range structure. The question is whether the G-phase can be termed a new type of glass. In this work, G-phase Cu is made in a molecular dynamics simulation using rapid quenching or isothermal annealing. Weak oscillations are found in the long-range atomic structure. The pseudo-fictive temperature is significantly lower than the Kauzmann temperature; fivefold twinning structures are distinguished in the G-phase whose constituent atoms are face-center-cubic or hexagonal-cubic-packed. This evidence suggests that G-phase Cu is not a glass. However, the G-phase is also metastable against crystallization. Therefore, G-phase Cu is neither a glass nor a crystal but belongs to a new mesophase.

Metallic Mimosa pudica: A 3D biomimetic buckling structure made of metallic glasses.

Metallic Mimosa pudica, a three-dimensional (3D) biomimetic structure made of metallic glass, is formed via laser patterning: Blooming, closing, and reversing of the metallic M. pudica can be controlled by an applied magnetic field or by manual reshaping. An array of laser-crystallized lines is written in a metallic glass ribbon. Changes in density and/or elastic modulus due to laser patterning result in an appropriate size mismatch between the shrunken crystalline regions and the glassy matrix. The residual stress and elastic distortion energy make the composite material to buckle within the elastic limit and to obey the minimum elastic energy criterion. This work not only provides a programming route for constructing buckling structures of metallic glasses but also provides clues for the study of materials with automatic functions desired in robotics, electronic devices, and, especially, medical devices in the field of medicine, such as vessel scaffolds and vascular filters, which require contactless expansion and contraction functions.

Aitongxiao improves pain symptoms of rats with cancer pain by reducing IL-1, TNF-α, and PGE2.

OBJECTIVE: To explore the mechanism of Aitongxiao in improving pain symptoms of rats with cancer pain. METHODS: Walker 256 breast cancer cells were injected into the right tibial bone marrow cavity of normal female rats to establish a rat model of tibial cancer pain. The rats with successful model replication were randomly divided into normal group (NG), Hank solution group (HSG), cancer pain model group (CPMG), and Aitongxiao+cancer pain model group (ATX+CPMG). The pain response score, mechanical pain hindpaw withdrawal threshold, and latent heat pain of rats were evaluated, and the changes of serum IL-1ß, TNF-α, PGE2 and blood cell counts of rats were detected. RESULTS: Compared with the NG, the pain response score was increased, the mechanical pain hindpaw withdrawal threshold and latent heat pain were decreased, and IL-1ß, TNF-α, and PGE2 were increased in CPMG. Compared with the CPMG, the pain response score was decreased, the mechanical pain hindpaw withdrawal threshold and latent heat pain were increased, and IL-1ß, TNF-α, and PGE2 were decreased in ATX+CPMG. There was no significant change in blood cell count in each group. CONCLUSION: Aitongxiao can improve the pain symptoms of rats with tibial cancer pain. Its mechanism may be related to the reduction of IL-1ß, TNF-α, and PGE2 levels.

Boson-peak-like anomaly caused by transverse phonon softening in strain glass.

Strain glass is a glassy state with frozen ferroelastic/martensitic nanodomains in shape memory alloys, yet its nature remains unclear. Here, we report a glassy feature in strain glass that was thought to be only present in structural glasses. An abnormal hump is observed in strain glass around 10 K upon normalizing the specific heat by cubed temperature, similar to the boson peak in metallic glass. The simulation studies show that this boson-peak-like anomaly is caused by the phonon softening of the non-transforming matrix surrounding martensitic domains, which occurs in a transverse acoustic branch not associated with the martensitic transformation displacements. Therefore, this anomaly neither is a relic of van Hove singularity nor can be explained by other theories relying on structural disorder, while it verifies a recent theoretical model without any assumptions of disorder. This work might provide fresh insights in understanding the nature of glassy states and associated vibrational properties.

3D genome architecture coordinates trans and cis regulation of differentially expressed ear and tassel genes in maize.

BACKGROUND: Maize ears and tassels are two separate types of inflorescence which are initiated by similar developmental processes but gradually develop distinct architectures. However, coordinated trans and cis regulation of differentially expressed genes determining ear and tassel architecture within the 3D genome context is largely unknown. RESULTS: We identify 56,055 and 52,633 open chromatin regions (OCRs) in developing maize ear and tassel primordia using ATAC-seq and characterize combinatorial epigenome features around these OCRs using ChIP-seq, Bisulfite-seq, and RNA-seq datasets. Our integrative analysis of coordinated epigenetic modification and transcription factor binding to OCRs highlights the cis and trans regulation of differentially expressed genes in ear and tassel controlling inflorescence architecture. We further systematically map chromatin interactions at high-resolution in corresponding tissues using in situ digestion-ligation-only Hi-C (DLO Hi-C). The extensive chromatin loops connecting OCRs and genes provide a 3D view on cis- and trans-regulatory modules responsible for ear- and tassel-specific gene expression. We find that intergenic SNPs tend to locate in distal OCRs, and our chromatin interaction maps provide a potential mechanism for trait-associated intergenic SNPs that may contribute to phenotypic variation by influencing target gene expression through chromatin loops. CONCLUSIONS: Our comprehensive epigenome annotations and 3D genome maps serve as valuable resource and provide a deep understanding of the complex regulatory mechanisms of genes underlying developmental and morphological diversities between maize ear and tassel.

BRIF-Seq: Bisulfite-Converted Randomly Integrated Fragments Sequencing at the Single-Cell Level.

Single-cell bisulfite sequencing (scBS-seq) was developed to assess DNA methylation heterogeneity in human and mouse. However, the reads are under-represented in regions with high DNA methylation, because these regions are usually fragmented into long segments and are seldom sequenced on the Illumina platform. To reduce the read distribution bias and maximize the use of these long segments, we developed bisulfite-converted randomly integrated fragments sequencing (BRIF-seq), a method with high rates of read mapping and genome coverage. Single microspore of maize, which has a highly methylated and repetitive genome, was used to perform BRIF-seq. High coverage of the haploid genome was obtained to evaluate the methylation states of CG, CHG, and CHH (H = A, C, or T). Compared with scBS-seq, BRIF-seq produced reads that were distributed more evenly across the genome, including regions with high DNA methylation. Surprisingly, the methylation rates among the four microspores within one tetrad were similar, but differed significantly among tetrads, suggesting that non-simultaneous methylation reprogramming could occur among tetrads. Similar levels of heterogeneity, which often occur in low-copy regions, were detected in different genetic backgrounds. These results suggest that BRIF-seq can be applied for single-cell methylome analysis of any species with diverse genetic backgrounds.

Subsurface reconstruction and saturation of surface bonds.

Surface reconstructions and stabilization mechanisms have been great challenges for insulators. Based on accurate determination of the long-sought atomic structure of the spinel (1 1 1) surface, here we show that the surface is stabilized by an unconventional mechanism. In general, solid surfaces have unsaturated chemical bonds and are prone to atomic reconstruction to saturate them. The spinel (1 1 1) surface, however, has the surface bonds fully saturated, while the unsaturated bonds remain only in the subsurface. It undergoes a reconstruction that keeps the topmost atomic layer unchanged, but has the subsurface atoms completely rearranged. Such a reconstruction results in a perfect compensation of the surface polarity and a large reduction in the surface energy. This work provides surprising insights into the surface stability and physical and chemical behaviors of complex oxides and insulators.

Roles of p38 and JNK protein kinase pathways activated by compound cantharidin capsules containing serum on proliferation inhibition and apoptosis of human gastric cancer cell line.

The aim of the present study was to investigate the inhibitory effect of compound cantharides capsules (CCCs) on the viability and apoptosis of human gastric cancer cell lines, BGC-823 and SGC-7901, and to detect its regulation of gene expression levels, as well as its inhibition mechanisms. Each cell line was grouped into a control group, CCC serum group, 5-fluorouracil (5-FU) group, combination therapy group (CCC serum + 5-FU) and serum control group. Growth curves were measured and flow cytometry was used to detect cell apoptosis and cell viability. The mRNA expression level of proliferation-related C-MYC and p53 genes were assayed by reverse transcription-quantitative polymerase chain reaction. Protein phosphorylation levels of proliferating cell nuclear antigen, p38 mitogen-activated protein kinase, extracellular signal-related kinase 1/2, c-Jun N-terminal kinase (JNK) and IκB were assayed by western blotting. The combined CCC serum and 5-FU group exhibited a higher inhibition rate in both cell lines and CCC serum therapy demonstrated a similar effect to 5-FU treatment, as demonstrated in the MTT and cell growth assay. Combined therapy significantly decreased the C-MYC mRNA expression levels and increased p53 mRNA expression levels (P<0.05). Combined therapy of 5-FU and CCC was more significant compared with CCC serum or 5-FU only (P<0.05). P38 and JNK-related protein phosphorylation are involved in apoptosis initiated by CCC combined 5-FU therapy. Combined therapy was able to significantly inhibit human gastric cancer cell growth (P<0.05), and advance cell apoptosis compared with CCC serum only. CCC serum resulted in downregulation of the c-Myc gene and upregulation of the p53 gene. p38 and JNK-related protein phosphorylation is involved in the inhibition of cell viability and apoptosis of human gastric cancer cell lines.

Cloning, molecular evolution and functional characterization of ZmbHLH16, the maize ortholog of OsTIP2 (OsbHLH142).

The transcription factor ZmbHLH16, the maize ortholog of OsTIP2 (OsbHLH142), was isolated in the present study. Tissue expression analysis showed that ZmbHLH16 is preferentially expressed in male reproductive organs. Subcellular location analysis of ZmbHLH16 via rice protoplast indicated that it is located in the nucleus. Through nucleotide variation analysis, 36 polymorphic sites in ZmbHLH16, including 23 single nucleotide polymorphisms and 13 InDels, were detected among 78 maize inbred lines. Neutrality tests and linkage disequilibrium analysis showed that ZmbHLH16 experienced no significant evolutionary pressure. Yeast one-hybrid experiment showed that the first 80 residues in the N-terminus of ZmbHLH16 had transactivation activity, whereas the full length did not. Genome-wide coexpression analysis showed that 395 genes were coexpressed with ZmbHLH16. Among these genes, the transcription factor ZmbHLH51 had similar expression pattern and identical subcellular localization to those of ZmbHLH16. Subsequently, the interaction between ZmbHLH51 and ZmbHLH16 was verified by yeast two-hybrid experiment. Through yeast two-hybrid analysis of series truncated ZmbHLH16 fragments, we found not only the typical bHLH domain [175-221 amino acids (a.a.)], but also that the 81-160 a.a. and 241-365 a.a. of ZmbHLH16 could interact with ZmbHLH51. All these results lay the foundation for further understanding the functions of ZmbHLH16.