Depletion of placental brain-derived neurotrophic factor (BDNF) is attributed to premature ovarian insufficiency (POI) in mice offspring.

INTRODUCTION: Premature ovarian insufficiency (POI) is one of the causes of female infertility. Unexplained POI is increasingly affecting women in their reproductive years. However, the etiology of POI is diverse and remains elusive. We and others have shown that brain-derived neurotrophic factor (BDNF) plays an important role in adult ovarian function. Here, we report on a novel role of BDNF in the Developmental Origins of POI. METHODS: Placental BDNF knockout mice were created using CRISPR/CAS9. Homozygous knockout (cKO(HO)) mice didn't survive, while heterozygous knockout (cKO(HE)) mice did. BDNF reduction in cKO(HE) mice was confirmed via immunohistochemistry and Western blots. Ovaries were collected from cKO(HE) mice at various ages, analyzing ovarian metrics, FSH expression, and litter sizes. In one-month-old mice, oocyte numbers were assessed using super-ovulation, and oocyte gene expression was analyzed with smart RNAseq. Ovaries of P7 mice were studied with SEM, and gene expression was confirmed with RT-qPCR. Alkaline phosphatase staining at E11.5 and immunofluorescence for cyclinD1 assessed germ cell number and cell proliferation. RESULTS: cKO(HE) mice had decreased ovarian function and litter size in adulthood. They were insensitive to ovulation induction drugs manifested by lower oocyte release after superovulation in one-month-old cKO(HE) mice. The transcriptome and SEM results indicate that mitochondria-mediated cell death or aging might occur in cKO(HE) ovaries. Decreased placental BDNF led to diminished primordial germ cell proliferation at E11.5 and ovarian reserve which may underlie POI in adulthood. CONCLUSION: The current results showed decreased placental BDNF diminished primordial germ cell proliferation in female fetuses during pregnancy and POI in adulthood. Our findings can provide insights into understanding the underlying mechanisms of POI.

Sphingosine kills intracellular Pseudomonas aeruginosa and Staphylococcus aureus.

Sphingosine has been previously shown to kill many strains of pathogenic bacteria including Pseudomonas aeruginosa, Staphyloccus aureus, Acinetobacter and atypical mycobacteria. However, these studies were performed on isolated or extracellular bacteria and it is unknown whether sphingosine also targets intracellular bacteria. Here, we demonstrate that exogenously-added sphingosine directly binds to extracellular P. aeruginosa and S. aureus, but also targets and binds to intracellular bacteria. Intracellular sphingosine and bacteria were identified by sequential immunostainings. We further show that exogenously-added sphingosine also kills intracellular P. aeruginosa and S. aureus using modified gentamycin assays. Intracellular killing of P. aeruginosa and S. aureus by sphingosine is not mediated by improved phagosomal-lysosomal fusion. In summary, our data indicate that sphingosine binds to and most likely also directly kills extra- and intracellular P. aeruginosa and S. aureus.

Sex-specific associations of adolescent motherhood with cognitive function, behavioral problems, and autistic-like traits in offspring and the mediating roles of family conflict and altered brain structure.

BACKGROUND: Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. METHODS: This study included 6952 children aged 9-11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20-35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations. RESULTS: Our results revealed that children of adolescent mothers had significantly lower cognitive scores (ß, - 2.11, 95% CI, - 2.90 to - 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study. CONCLUSIONS: Our results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood.

Perinatal exposure to perfluorooctane sulfonate and the risk of hepatic inflammation in rat offspring: Perturbation of gut-liver crosstalk.

Perfluorooctane sulfonate (PFOS) exposure is associated with harmful hepatic outcomes. Growing evidence indicates that crosstalk between the gut microbiome, immune system, and liver plays a vital role in the pathogenesis of liver diseases. However, the underlying mechanism is not fully understood. In the present study, we aimed to investigate the effects of PFOS exposure during pregnancy and lactation on hepatic inflammation in rat offspring. Features of hepatic inflammation and increased levels of aspartate-amino transferase (AST) were found in pups on postnatal day 28 (PND28) in PFOS-exposed groups. Gut microbiota analysis identified Chitinophaga, Ralstonia, and Alloprevotella as the key genera in distinguishing the PFOS-exposed group from the control group. Metabolic and transcriptomic analyses found that PFOS exposure resulted in 48 differentially expressed metabolites (DEMs) in the serum, 62 DEMs in the liver, and 289 differentially expressed genes (DEGs) in the liver of PND28 pups. The immune response is significantly enriched in PFOS-exposed liver on PND28; multi-omics analysis indicated that PFOS might lead to immune response perturbation by disturbing the metabolic profiling in the liver. The changed gut microbiota was significantly related to the serum level of the liver function index. Specifically, Alloprevotella, Chitinophage, Ruminococcus, and Allobaculum were significantly associated with the metabolic abundance changes of 4-Hydroxydebrisoquine, L-Norvaline, and Eremopetasinorol, and the gene expression changes of Acat211, Msmol, Idi1, Sqle, and Gadd45b in the liver. These findings suggest that early-life PFOS exposure may be associated with adverse hepatic inflammation in young offspring via disruption of the gut-liver crosstalk, which may provide mechanistic clues for clarifying the hepatotoxicity in offspring associated with perinatal PFOS exposure.

Buried interface modification and light outcoupling strategy for efficient blue perovskite light-emitting diodes.

Perovskite light-emitting diodes (PeLEDs) exhibit remarkable potential in the field of displays and solid-state lighting. However, blue PeLEDs, a key element for practical applications, still lag behind their green and red counterparts, due to a combination of strong nonradiative recombination losses and unoptimized device structures. In this report, we propose a buried interface modification strategy to address these challenges by focusing on the bottom-hole transport layer (HTL) of the PeLEDs. On the one hand, a multifunctional molecule, aminoacetic acid hydrochloride (AACl), is introduced to modify the HTL/perovskite interface to regulate the perovskite crystallization. Experimental investigations and theoretical calculations demonstrate that AACl can effectively reduce the nonradiative recombination losses in bulk perovskites by suppressing the growth of low-n perovskite phases and also the losses at the bottom interface by passivating interfacial defects. On the other hand, a self-assembly nanomesh structure is ingeniously developed within the HTLs. This nanomesh structure is meticulously crafted through the blending of poly-(9,9-dioctyl-fluorene-co-N-(4-butyl phenyl) diphenylamine) and poly (n-vinyl carbazole), significantly enhancing the light outcoupling efficiency in PeLEDs. As a result, our blue PeLEDs achieve remarkable external quantum efficiencies, 20.4% at 487 nm and 12.5% at 470 nm, which are among the highest reported values. Our results offer valuable insights and effective methods for achieving high-performance blue PeLEDs.

Comparing the effects of magnetite-mediated direct interspecies electron transfer with biogas mixing-driven interspecies hydrogen transfer on anaerobic digestion.

Although the promotive effect of direct interspecies electron transfer (DIET) on methane production has been well-documented, the practical applicability of DIET in different scenarios have not yet been systematically studied. This study compared the effects of magnetite-mediated DIET with conventional biogas mixing-driven interspecies hydrogen transfer (IHT) on anaerobic digestion (AD) of swine manure (SM). Compared with control, magnetite supplementation, biogas circulation, and their integration enhanced the CH4 yield by 19.3%, 25.9%, and 26.2%, respectively. Magnetite mainly enriched DIET-related syntrophic bacteria (Anaerolineae and Synergistia) and methanogens (Methanosarcina) to accelerate acidification and establish DIET, while biogas circulation mainly enriched hydrolytic bacteria (Clostridia) and hydrogenotrophic methanogens (Methanolinea and Methanobacterium) to promote hydrolysis and accelerate IHT. Coupling magnetite addition with biogas circulation led to the enrichment of the above six microorganisms to different extents. The effectiveness of the strategies for lowering the H2 pressure followed: magnetite + biogas circulation ≈ biogas circulation > magnetite. Under stress-free environment, the enhancement effect of magnetite-induced DIET was not even as pronounced as biogas circulation-a simple and common mixing strategy in commercial AD plants, and the promotion effect of magnetite was insignificant in the well-mixed digesters. In short, the magnetite-mediated DIET is not always effective in improving AD of SM.

Multi-omics reveal disturbance of glucose homeostasis in pregnant rats exposed to short-chain perfluorobutanesulfonic acid.

Perfluorobutanesulfonic acid (PFBS), a short-chain alternative to perfluorooctanesulfonic acid (PFOS), is widely used in various products and is increasingly present in environmental media and human bodies. Recent epidemiological findings have raised concerns about its potential adverse health effects, although the specific toxic mechanism remains unclear. This study aimed to investigate the metabolic toxicity of gestational PFBS exposure in maternal rats. Pregnant Sprague Dawley (SD) rats were randomly assigned to three groups and administered either 3% starch gel (control), 5, or 50 mg/kg bw·d PFBS. Oral glucose tolerance tests (OGTT) and lipid profiles were measured, and integrated omics analysis (transcriptomics and non-targeted metabolomics) was employed to identify changes in genes and metabolites and their relationships with metabolic phenotypes. The results revealed that rats exposed to 50 mg/kg bw·d PFBS exhibited a significant decrease in 1-h glucose levels and the area under the curve (AUC) of OGTT compared with the starch group. Transcriptomics analysis indicated significant alterations in gene expression related to cytochrome P450 exogenous metabolism, glutathione metabolism, bile acid secretion, tumor pathways, and retinol metabolism. Differentially expressed metabolites (DEMs) were enriched in pathways such as pyruvate metabolism, the glucagon signaling pathway, central carbon metabolism in cancer, and the citric acid cycle. Co-enrichment analysis and pairwise correlation analysis among genes, metabolites, and outcomes identified several differentially expressed genes (DEGs), including Gstm1, Kit, Adcy1, Gck, Ppp1r3c, Ppp1r3d, and DEMs such as fumaric acid, L-lactic acid, 4-hydroxynonenal, and acetylvalerenolic acid. These DEGs and DEMs may play a role in the modulation of glucolipid metabolic pathways. In conclusion, our results suggest that gestational exposure to PFBS may induce molecular perturbations in glucose homeostasis. These findings provide insights into the potential mechanisms contributing to the heightened risk of abnormal glucose tolerance associated with PFBS exposure.

The Gradient Effect on Cyclic Behavior of 316L Stainless Steel in the Ultrasonic Bending Test.

Nanoindentation measurements were conducted to investigate the high-cycle response of 316L stainless steel in bending fatigue. Hardness variation owing to the gradient flexure stress amplitude for different curvatures was plotted along with the thickness and length, respectively. Scanning electron microscopy (SEM) was subsequently conducted to explore the deformation characteristics in multiple layers, which had cyclic gradient stress, on the cross-section of specimens. The nanoindentation results indicated that the cyclic hardening response of 316L stainless steel is correlated with the level of stress amplitude in the high-cycle fatigue (HCF) regime. Furthermore, an analytical model was proposed to clarify the relationship between nanohardness and stress amplitude. Finally, the evolution of damage accumulation due to irreversible plastic deformation is continuous during stress reduction up to the neighboring zone at the neutral surface of the flexure beam in some individual grains.

Correction: Li et al. Recovery Behavior of the Macro-Cracks in Elevated Temperature-Damaged Concrete after Post-Fire Curing. Materials 2022, 15, 5673.

Following publication, concerns relating to the relevance of a number of citations recommend by a peer reviewer were brought to the attention of the Editorial Office [...].

The ω-3 Polyunsaturated Fatty Acid Docosahexaenoic Acid Enhances NK-Cell Antitumor Effector Functions.

ω-3 polyunsaturated fatty acids (PUFA) are known to directly repress tumor development and progression. In this study, we explored whether docosahexaenoic acid (DHA), a type of ω-3 PUFA, had an immunomodulatory role in inhibiting tumor growth in immunocompetent mice. The number of natural killer (NK) cells but not the number of T or B cells was decreased by DHA supplementation in various tissues under physiologic conditions. Although the frequency and number of NK cells were comparable, IFNγ production by NK cells in both the spleen and lung was increased in DHA-supplemented mice in the mouse B16F10 melanoma tumor model. Single-cell RNA sequencing revealed that DHA promoted effector function and oxidative phosphorylation in NK cells but had no obvious effects on other immune cells. Using Rag2-/- mice and NK-cell depletion by PK136 antibody injection, we demonstrated that the suppression of B16F10 melanoma tumor growth in the lung by DHA supplementation was dependent mainly on NK cells. In vitro experiments showed that DHA directly enhanced IFNγ production, CD107a expression, and mitochondrial oxidative phosphorylation (OXPHOS) activity and slightly increased proliferator-activated receptor gamma coactivator-1α (PGC-1α) protein expression in NK cells. The PGC-1α inhibitor SR-18292 in vitro and NK cell-specific knockout of PGC-1α in mice reversed the antitumor effects of DHA. In summary, our findings broaden the current knowledge on how DHA supplementation protects against cancer growth from the perspective of immunomodulation by upregulating PGC-1α signaling-mediated mitochondrial OXPHOS activity in NK cells.

Single-cell multi-omics analysis of lineage development and spatial organization in the human fetal cerebellum.

Human cerebellum encompasses numerous neurons, exhibiting a distinct developmental paradigm from cerebrum. Here we conducted scRNA-seq, scATAC-seq and spatial transcriptomic analyses of fetal samples from gestational week (GW) 13 to 18 to explore the emergence of cellular diversity and developmental programs in the developing human cerebellum. We identified transitory granule cell progenitors that are conserved across species. Special patterns in both granule cells and Purkinje cells were dissected multidimensionally. Species-specific gene expression patterns of cerebellar lobes were characterized and we found that PARM1 exhibited inconsistent distribution in human and mouse granule cells. A novel cluster of potential neuroepithelium at the rhombic lip was identified. We also resolved various subtypes of Purkinje cells and unipolar brush cells and revealed gene regulatory networks controlling their diversification. Therefore, our study offers a valuable multi-omics landscape of human fetal cerebellum and advances our understanding of development and spatial organization of human cerebellum.

Interactive effects of grassland utilization and climatic factors govern the plant diversity-soil C relationship in steppe of North China.

The relationship between plant diversity and the ecosystem carbon pool is important for understanding the role of biodiversity in regulating ecosystem functions. However, it is not clear how the relationship between plant diversity and soil carbon content changes under different grassland use patterns. In a 3-year study from 2013 to 2015, we investigated plant diversity and soil total carbon (TC) content of grasslands in northern China under different grassland utilization methods (grazing, mowing, and enclosure) and climatic conditions. Shannon-Wiener and Species richness index of grassland were significantly decreased by grazing and mowing. Plant diversity was positively correlated with annual precipitation (AP) and negatively correlated with annual mean temperature (AMT). AP was the primary regulator of plant diversity. Grazing and mowing decreased TC levels in grasslands compared with enclosures, especially in topsoil (0-20 cm). The average TC content was decreased by 58 % and 36 % in the 0-10 cm soil layer, while it was decreased by 68 % and 39 % in 10-20 cm soil layer. TC was positively correlated with AP and negatively correlated with AMT. Principal component analysis (PCA) showed that plant diversity was positively correlated with soil TC, and the correlation decreased with an increase in the soil depth. Overall, this study provides a theoretical basis for predicting soil carbon storage in grasslands under human disturbances and climate change impacts.

Single-cell landscape of the cellular microenvironment in three different colonic polyp subtypes in children.

BACKGROUND: The understanding of the heterogeneous cellular microenvironment of colonic polyps in paediatric patients with solitary juvenile polyps (SJPs), polyposis syndrome (PJS) and Peutz-Jeghers syndrome (PJS) remains limited. METHODS: We conducted single-cell RNA sequencing and multiplexed immunohistochemistry (mIHC) analyses on both normal colonic tissue and different types of colonic polyps obtained from paediatric patients. RESULTS: We identified both shared and disease-specific cell subsets and expression patterns that played important roles in shaping the unique cellular microenvironments observed in each polyp subtype. As such, increased myeloid, endothelial and epithelial cells were the most prominent features of SJP, JPS and PJS polyps, respectively. Noticeably, memory B cells were increased, and a cluster of epithelial-mesenchymal transition (EMT)-like colonocytes existed across all polyp subtypes. Abundant neutrophil infiltration was observed in SJP polyps, while CX3CR1hi CD8+ T cells and regulatory T cells (Tregs) were predominant in SJP and JPS polyps, while GZMAhi natural killer T cells were predominant in PJS polyps. Compared with normal colonic tissues, myeloid cells exhibited specific induction of genes involved in chemotaxis and interferon-related pathways in SJP polyps, whereas fibroblasts in JPS polyps had upregulation of myofiber-associated genes and epithelial cells in PJS polyps exhibited induction of a series of nutrient absorption-related genes. In addition, the TNF-α response was uniformly upregulated in most cell subsets across all polyp subtypes, while endothelial cells and fibroblasts separately showed upregulated cell adhesion and EMT signalling in SJP and JPS polyps. Cell-cell interaction network analysis showed markedly enhanced intercellular communication, such as TNF, VEGF, CXCL and collagen signalling networks, among most cell subsets in polyps, especially SJP and JPS polyps. CONCLUSION: These findings strengthen our understanding of the heterogeneous cellular microenvironment of polyp subtypes and identify potential therapeutic approaches to reduce the recurrence of polyps in children.

Treatment of Staphylococcus aureus infection with sphingosine in ex vivo perfused and ventilated lungs.

BACKGROUND: Ex vivo lung perfusion (EVLP) has expanded the donor pool for lung transplantation. Pulmonary Staphylococcus aureus infection, especially that caused by multidrug-resistant strains, is a severe threat to posttransplantation outcomes. Sphingosine is a lipid compound that exhibits broad-spectrum antibacterial activity. Therefore, we aimed to evaluate the effects of S aureus infection on EVLP and whether sphingosine administration during EVLP prevents infection with S aureus. METHODS: Eighteen pigs were randomly assigned to 3 groups: uninfected, infected with S aureus with NaCl treatment, or infected with sphingosine treatment. Bacterial numbers were determined before and after treatment. Sphingosine concentrations in the lung tissues were determined using biochemical assays. Lung histology, lung physiological parameters, perfusate content, lung weight, and cell death were measured to analyze the effects of infection and sphingosine administration on EVLP. RESULTS: Sphingosine administration significantly reduced the bacterial load. The concentration of sphingosine in the bronchial epithelium was elevated after sphingosine administration. S aureus infection increased pulmonary artery pressure and pulmonary vascular resistance. Lung edema, histology scores, lactate and lactate dehydrogenase levels in the perfusate, ΔPO2 in the perfusate, static lung compliance, and lung peak airway pressure did not differ among the groups. CONCLUSIONS: Infection of S aureus did not affect the lung function during EVLP but induced higher pulmonary artery pressure and pulmonary vascular resistance. Administration of sphingosine effectively eliminated S aureus without side effects in isolated, perfused, and ventilated pig lungs.

Maternal urban particulate matter (SRM 1648a) exposure disrupted the cellular immune homeostasis during early life: The potential attribution of altered placental transcriptome profile.

Ambient fine particular matter (PM2.5) exposure has been associated with numerous adverse effects including triggering functional disorders of the placenta and inducing immune imbalance in offspring. However, how maternal PM2.5 exposure impacts immune development during early life is not fully understood. In the current study, we exposed mice with low-, middle-, and high-dose PM2.5 during pregnancy to investigate the potential link between the transcriptional changes in the placenta and immune imbalance in mice offspring induced by PM2.5 exposures. Using flow cytometry, we found that the proportions of B cells, CD3+CD4+ T cells, CD3+CD8+ T cells, and macrophage (Mφ) cells were altered in the blood of PM2.5-exposed mice pups but not dendritic cells (DCs) and natural killer cells (NKs). Using bulk RNA sequencing, we found that PM2.5 exposure altered the transcriptional profile which indicated an inhibition of the complement and coagulation cascades in the placenta. Weighted gene co-expression network analysis (WGCNA) revealed the potential crosstalk between the perturbation of placental gene expression and the changes of immune cell subsets in pups on postnatal day 10 (PND10). Specifically, WGCNA identified a cluster of genes including Defb15, Defb20, Defb25, Cst8, Cst12, and Adam7 that might regulate the core immune cell types in PND10 pups. Although the underlying mechanisms of how maternal PM2.5 exposure induces peripheral lymphocyte disturbance in offspring still remain much unknown, our findings here shed light on the potential role of placental dysfunction in these adverse effects.

Transcriptomic and metabolomic profile changes in the liver of Sprague Dawley rat offspring after maternal PFOS exposure during gestation and lactation.

Epidemiological and experimental research has indicated an association between perfluorooctane sulfonate (PFOS) exposure and liver disease. However, the potential hepatotoxic effects and mechanisms of low-level prenatal PFOS exposure in offspring remain ambiguous. The objective of this research was to examine the alterations in liver transcriptomic and metabolomic profiles in offspring rats at postnatal day (PND) 30 following gestational and lactational exposure to PFOS (from gestational day 1 to 20 and PND 1 to 21). Pregnant Sprague-Dawley rats were separated into a control group (3% starch gel solution, oral gavage) and a PFOS exposure group (0.03 mg/kg body weight per day, oral gavage). Histopathological changes in liver sections were observed by hematoxylin and eosin staining. Biochemical analysis was conducted to evaluate changes in glucose and lipid metabolism. Transcriptomic and metabolomic analyses were utilized to identify significant genes and metabolites associated with alterations of liver glucose and lipid metabolism through an integrated multi-omics analysis. No significant differences were found in the measured biochemical parameters. In total, 167 significant differentially expressed genes (DEGs) related to processes such as steroid biosynthesis, PPAR signaling pathway, and fat digestion and absorption were identified in offspring rats in the PFOS exposure group. Ninety-five altered metabolites were exhibited in the PFOS exposure group, such as heptaethylene glycol, lysoPE (0:0/18:0), lucidenic acid K, and p-Cresol sulfate. DEGs associated with steroid biosynthesis, PPAR signaling pathway, fat digestion and absorption were significantly upregulated in the PFOS exposure group (P < 0.05). The analysis of correlations indicated that there was a significant inverse correlation between all identified differential metabolites and the levels of fasting blood glucose, high-density lipoprotein, and triglycerides in the PFOS exposure group (P < 0.05). Our findings demystify that early-life PFOS exposure can lead to alterations in transcriptomic and metabolomic profiles in the offspring's liver, which provided mechanistic insights into the potential hepatotoxicity and developmental toxicity associated with environmentally relevant levels of PFOS exposure.

Identification and validation of major-effect quantitative trait locus QMS-5B associated with male sterility in photo-thermo-sensitive genic male sterile wheat.

KEY MESSAGE: QMS-5B, a major QTL for photo-thermo-sensitive genic male sterility in wheat, was fine mapped in a 2.15 Mb region harboring a serine/threonine protein kinase gene TraesCS5B03G0887500, which was the most likely candidate gene. Genic male sterility is an essential trait in the utilization of heterosis and hybrid seed production for wheat. Currently, genic male sterile genes have been reported in wheat mutants, but the sterile genes controlling photo-thermo-sensitive genic male sterility in wheat have not been studied systematically. Here, 235 doubled haploid lines derived from a cross between photo-thermo-sensitive genic male sterile line BS462 and its restorer line CP279 were used to map male sterile gene by GenoBaits® Wheat 100 K Panel, bulked segregant exome sequencing (BSE-Seq) and wheat 660 K array. As a result, the major stable QTL on chromosome 5B, QMS-5B, was identified in all four environments, accounting for 7.3-36.4% of the phenotypic variances. Ulteriorly, QMS-5B was delimited to an approximate 2.15 Mb physical interval between KASP-5B5 and KASP-5B6 using kompetitive allele-specific PCR (KASP) markers. Within the interval, twenty-nine high-confidence genes were predicted according to Chinese Spring RefSeq v2.1. TraesCS5B03G0887500, encoding a serine/threonine protein kinase, was identified as the most likely candidate gene for QMS-5B based on weighted gene co-expression network analysis. Expression analysis confirmed that TraesCS5B03G0887500 was significantly differentially expressed in anthers of BS462 and CP279 at different stages under fertile and sterile environments. In addition, flanking KASP marker KASP-5B6 can effectively genotype male sterile lines and restorer lines, and can be used for molecular marker-assisted selection. This study provides insights into for exploring the mechanism of photo-thermo-sensitive genic male sterility in wheat.

Composition of ex vivo perfusion solutions and kinetics define differential cytokine/chemokine secretion in a porcine cardiac arrest model of lung preservation.

Background: Ex vivo lung perfusion (EVLP) uses continuous normothermic perfusion to reduce ischemic damage and to improve post-transplant outcomes, specifically for marginal donor lungs after the donation after circulatory death. Despite major efforts, the optimal perfusion protocol and the composition of the perfusate in clinical lung transplantation have not been identified. Our study aims to compare the concentration levels of cytokine/chemokine in different perfusion solutions during EVLP, after 1 and 9 h of cold static preservation (CSP) in a porcine cardiac arrest model, and to correlate inflammatory parameters to oxygenation capacities. Methods: Following cardiac arrest, the lungs were harvested and were categorized into two groups: immediate (I-EVLP) and delayed EVLP (D-EVLP), after 1 and 9 h of CSP, respectively. The D-EVLP lungs were perfused with either Steen or modified Custodiol-N solution containing only dextran (CD) or dextran and albumin (CDA). The cytokine/chemokine levels were analyzed at baseline (0 h) and after 1 and 4 h of EVLP using Luminex-based multiplex assays. Results: Within 4 h of EVLP, the concentration levels of TNF-α, IL-6, CXCL8, IFN-γ, IL-1α, and IL-1ß increased significantly (P < 0.05) in all experimental groups. The CD solution contained lower concentration levels of TNF-α, IL-6, CXCL8, IFN-γ, IL-2, IL-12, IL-10, IL-4, IL-1RA, and IL-18 (P < 0.05) compared with those of the Steen solution. The concentration levels of all experimental groups have correlated negatively with the oxygenation capacity values (P < 0.05). Protein concentration levels did not reach statistical significance for I-EVLP vs. D-EVLP and CD vs. CDA solutions. Conclusion: In a porcine cardiac arrest model, a longer period of CSP prior to EVLP did not result in an enhanced protein secretion into perfusates. The CD solution reduced the cytokine/chemokine secretion most probably by iron chelators and/or by the protecting effects of dextran. Supplementing with albumin did not further reduce the cytokine/chemokine secretion into perfusates. These findings may help in optimizing the preservation procedure of the lungs, thereby increasing the donor pool of organs.

Characterization and expression analysis of chalcone synthase gene family members suggested their roles in the male sterility of a wheat temperature-sensitive genic male sterile (TGMS) line.

Chalcone synthase (CHS), also known as the plants-specific type III polyketide synthases (PKSs), catalyzes the first key step in the biosynthesis of plant flavonoids. Flavonoids are one of the most important secondary metabolites which participate in flower pigmentation and pollen fertility. Recent reports have demonstrated the role of the CHS family in plant pollen exine formation. This study focused on the potential roles of CHS in the pollen exine formation of wheat. In the present study, a genome-wide investigation of the CHS family was carried out, and 87 CHS genes were identified in wheat. TaCHS3, TaCHS10, and TaCHS13 are wheat orthologs of Arabidopsis LESS ADHESIVE POLLEN (LAP5); TaCHS58, TaCHS64, and TaCHS67 are wheat orthologs of AtLAP6. TaCHS3, TaCHS10, and TaCHS67 showed anther-specific patterns. The expression of TaCHS3, TaCHS10, and TaCHS67 was positively co-expressed with sporopollenin biosynthetic genes, including TaCYP703A2, TaCYP704B1, TaDRL1, TaTKPR2, and TaMS2. Coincidently, the expression of TaCHS3, TaCHS10, and TaCHS67, together with those sporopollenin biosynthetic genes, were repressed at the tetrads and uninucleate stages in the temperature-sensitive genic male-sterile (TGMS) line BS366 under sterile conditions. Wheat anther-specific CHS genes might participate in the exine formation of BS366 through co-expressing with sporopollenin biosynthetic genes, which will undoubtedly provide knowledge of the roles of CHS in wheat pollen development.

Transcriptomics integrated with metabolomics reveals perfluorobutane sulfonate (PFBS) exposure effect during pregnancy and lactation on lipid metabolism in rat offspring.

Emerging epidemiological evidence indicates potential associations between gestational perfluorobutane sulfonate (PFBS) exposure and adverse metabolic outcomes in offspring. However, the underlying mechanisms remain unclear. Our study aimed to investigate PFBS exposure effects during pregnancy and lactation on rat offspring lipid profiles and the possible underlying mechanisms. Although the biochemical index difference including total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alanine amino transaminase (ALT), aspartate amino transferase (AST), and fasting blood glucose between exposed groups and the control group was not significant, transcriptome analyses showed that the differentially expressed genes (DEGs) in the 50 mg/kg/day PFBS exposure group were significantly related to protein digestion and absorption, peroxisome proliferator activated-receptor (PPAR) signaling pathway, xenobiotic metabolism by cytochrome P450, glycine, serine and threonine metabolism, ß-alanine metabolism, bile secretion, unsaturated fatty acid (FA) biosynthesis, and alanine, aspartate and glutamate metabolism. Untargeted metabolomics analyses identified 17 differential metabolites in the 50 mg/kg/day PFBS exposure group. Among these, phosphatidylserine [PS (18:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z))], lysoPE (18:1(11Z)/0:0), and PS (14:0/20:4(5Z,8Z,11Z,14Z)) were significantly correlated with phospholipid metabolism disorders. Correlation analysis indicated the DEGs, including FA binding protein (Fabp4), spermine oxidase (Smox), Fabp2, acyl-CoA thioesterase 5 (Acot5), sarcosine dehydrogenase (Sardh), and amine oxidase, copper-containing 3 (Aoc3) that significantly enriched in xenobiotic metabolism by cytochrome P450 and glycine, serine, and threonine metabolism signaling pathways were highly related to the differential metabolite pantetheine 4'-phosphate. Pantetheine 4'-phosphate was significantly negatively associated with non-high-density lipoprotein (non-HDL) and TC levels. Collectively, our study indicated that maternal PFBS exposure at a relatively low level could alter gene expression and metabolic molecules in lipid metabolism-related pathway series in rat offspring, although the effects on metabolic phenotypes were not significant within the limited observational period, using group-wise and trend analyses.