Dissection of transcriptome dysregulation and immune characterization in women with germline BRCA1 mutation at single-cell resolution.

BACKGROUND: High-grade serous carcinoma (HGSC) is the most frequent and lethal type of ovarian cancer. It has been proposed that tubal secretory cells are the origin of ovarian HGSC in women with familial BRCA1/2 mutations. However, the molecular changes underlying malignant transformation remain unknown. METHOD: We performed single-cell RNA and T cell receptor sequencing of tubal fimbriated ends from 3 BRCA1 germline mutation carriers (BRCA1 carriers) and 3 normal controls with no high-risk history (non-BRCA1 carriers). RESULTS: Exploring the transcriptomes of 19,008 cells, predominantly from BRCA1+ samples, we identified 5 major cell populations in the fallopian tubal mucosae. The secretory cells of BRCA1+ samples had differentially expressed genes involved in tumor growth and regulation, chemokine signaling, and antigen presentation compared to the wild-type BRCA1 controls. There are several novel findings in this study. First, a subset of the fallopian tubal secretory cells from one BRCA1 carrier exhibited an epithelial-to-mesenchymal transition (EMT) phenotype, which was also present in the mucosal fibroblasts. Second, we identified a previously unreported phenotypic split of the EMT secretory cells with distinct evolutionary endpoints. Third, we observed increased clonal expansion among the CD8+ T cell population from BRCA1+ carriers. Among those clonally expanded CD8+ T cells, PD-1 was significantly increased in tubal mucosae of BRCA1+ patients compared with that of normal controls, indicating that T cell exhaustion may occur before the development of any premalignant or malignant lesions. CONCLUSION: These results indicate that EMT and immune evasion in normal-looking tubal mucosae may represent early events leading to the development of HGSC in women with BRCA1 germline mutation. Our findings provide a probable molecular mechanism explaining why some, but not all, women with BRCA1 germline mutation present with early development and rapid dissemination of HGSC.

Selenium regulates the mitogen-activated protein kinase pathway to protect broilers from hexavalent chromium-induced kidney dysfunction and apoptosis.

Hexavalent chromium [Cr (VI)] is a common environmental pollutant. Although selenium (Se) can antagonize the toxicity of Cr (VI), the specific underlying mechanism has not been identified. To investigate this mechanism, we used potassium dichromate (K2Cr2O7) and selenium-rich yeast (SeY) to construct single Cr (VI)- and combined Se/Cr (VI)-exposed broiler models during a 42-day period. Broilers were randomly assigned to the control (C), SeY (Se), SeY + Cr (VI) (Se/Cr), and Cr (VI) (Cr) groups. The antagonistic mechanisms of Se and Cr (VI) were evaluated using histopathological evaluation, serum and tissue biochemical tests, real-time fluorescence quantitative polymerase chain reaction, and western blotting. The results suggested that Se alleviated the morphological and structural damage to renal tubules and glomeruli, while reducing the organ index, creatinine levels, and blood urea nitrogen levels in the kidneys of Cr (VI)-exposed broilers. Furthermore, Cr (VI) reduced the levels of superoxide dismutase and glutathione, and increased the levels of malondialdehyde, in broiler kidney tissues. However, Se alleviated Cr (VI)-induced oxidative stress by increasing the levels of superoxide dismutase and glutathione, and decreasing the levels of malondialdehyde, within a certain range. Compared to the C group, the levels of p38, JNK, p-p38, p-JNK, p-p38/p38, and p-JNK/JNK significantly increased, whereas those of ERK, p-ERK, and p-ERK/ERK decreased, in the Cr group. Compared to the Cr group, the levels of p38, JNK, p-p38, p-JNK, p-p38/p38, and p-JNK/JNK significantly decreased, whereas those of ERK, p-ERK, and p-ERK/ERK increased, in the Se/Cr group. Furthermore, the levels of p53, c-Myc, Bax, Cyt-c, caspase-9, and caspase-3 significantly increased, and those of Bcl-2 and Bcl-2/Bax significantly decreased, following Cr (VI) exposure, while Se restored the expression of these genes. In conclusion, our findings suggest that SeY can protect against Cr (VI)-induced dysfunction and apoptosis by regulating the mitogen-activated protein kinase pathway activated by oxidative stress in broiler kidney tissues.

Clinical efficacy evaluation of Erlotinib Combined with Concurrent Chemoradiotherapy in the treatment of locally advanced Pancreatic Cancer.

OBJECTIVE: To evaluate the clinical effects of erlotinib combined with concurrent chemoradiotherapy in the treatment of locally advanced pancreatic cancer. METHODS: Eighty patients with locally advanced pancreatic cancer who attended Shijiazhuang People's Hospital or Anhui Cancer Hospital between January 2018 and January 2020 were randomly divided into two groups, with 40 cases in each group. Patients in the control group were treated with concurrent chemoradiotherapy, while those in the experimental group were treated with erlotinib tablets based on the treatment regimen of the control group. Anti-tumor efficacy evaluation was conducted for all patients in both groups, and the adverse drug reactions, improvement of performance status after treatment were compared and analyzed between the two groups. RESULTS: The overall response rate of the experimental group was 47.5%, which was significantly better than the 25% of the control group (p=0.03). The incidence of adverse drug reactions in the experimental group was 40%, while that in the control group was 30%. The incidence of adverse drug reactions in the experimental group was higher than that in the control group, but there was no statistical significance (p=0.34). Moreover, the improvement rate of performance status score in the experimental group was significantly higher than that in the control group (p=0.00). CONCLUSION: Erlotinib combined with concurrent chemoradiotherapy has been preliminarily proved to be safe and effective in the treatment of locally advanced pancreatic cancer, which can improve the physical condition of patients to a certain extent without significantly increasing adverse reactions.

Transcription factor OsMADS25 improves rice tolerance to cold stress.

Cold stress is the limiting factor of rice growth and production, and it is important to clone cold stress tolerant genes and cultivate cold tolerance rice varieties. The MADS transcription factors play an important role in abiotic stress signaling in rice. This study showed that OsMADS25 was up-regulated by low temperature and abscisic acid (ABA), suggesting that OsMADS25 may be involved in ABA-dependent signaling. The OsMADS25 overexpression vector, pCambia1300-221-OsMADS25-Flag, was constructed and introduced into the rice variety Zhonghua 11 (ZH11) through Agrobacterium tumefacian-mediated genetic transformation. Two homozygous lines with high expression levels were selected for phenotypic identification. OsMADS25 overexpression lines show significantly improved cold stress tolerance and the sensitivity to ABA at the seedling stage of rice. Reactive oxygen species (ROS) was detected by diaminobenzidine (DAB) staining and nitroblue tetrazolium (NBT) staining. After treatment with cold stress, little ROS accumulation was observed in OsMADS25 overexpression lines compared to wild-type ZH11. In conclusion, OsMADS25 plays a role in scavenging reactive oxygen species (ROS) and could improve rice tolerance to cold stress involved in ABA-dependent pathway.

Study on the nutritional value and ruminal degradation characteristics of fermented waste vinegar residue by N. sitophila.

Chemical composition and rumen degradability of waste vinegar residue (WVR) as roughage feed used for mutton sheep were evaluated in this work. Compared with the unfermented WVR, the WVR fermented by N. sitophila had more (P < 0.01) ash, crude protein (CP), and true protein (TP), less (P < 0.01) ether extract (EE), and significantly more carotenoid by about 27 times. But the contents of dry matter (DM), crude fiber (CF), neutral detergent fiber (NDF), and acid detergent fiber (ADF) had no obvious differences (P > 0.05) between unfermented and fermented WVR. The results suggested that the nutritional value of fermented WVR was higher for mutton sheep as roughage feed than that of unfermented WVR. The effective degradability (ED) of DM was higher (P < 0.05) in sheep with fermented WVR-based diet. The ED of CP and NDF of fermented WVR was reduced (P < 0.01) compared with the unfermented WVR. The results further suggested that the fermentation improved the degradability of WVR, and the rumen degradability of protein by ruminal flora decreased in fermented WVR, saving more protein for the sheep post-ruminal digestion and absorption. Furthermore, the results presented here clearly indicated the potential of fermented WVR by N. sitophila as an unconventional and functional feedstuff with rich carotenoid for ruminants, which could reduce WVR discharge in vinegar brewing industry and improve ruminant production. This work laid a foundation for the development of ruminant carotenoid functional feed.

PAFAH1B2 is a HIF1a target gene and promotes metastasis in pancreatic cancer.

Platelet-activating factor acetylhydrolase IB subunit beta (PAFAH1B2) plays important roles in inflammation and anaphylaxis. However, its primary function in pancreatic cancer remains unclear. In the current study, we report that PAFAH1B2 is overexpressed in pancreatic ductal adenocarcinoma (PDAC) and correlated inversely with patient survival. PAFAH1B2 overexpression induced epithelial-mesenchymal transition (EMT), migration and invasion in vitro and metastasis in vivo. Conversely, silencing PAFAH1B2 inhibited these aggressive phenotypes. Moreover, PAFAH1B2 overexpression in PDAC cells was directly mediated by HIF1a. PAFAH1B2 expression in PDAC clinical specimens correlated positively with HIF1a expression. Overall, our results defined PAFAH1B2 as a target gene of HIF1a and a critical driver of PDAC metastatic behaviors.

Cold stress tolerance in rice: physiological changes, molecular mechanism, and future prospects.

Low temperature is a major factor affecting rice geographical distribution growth, development, and productivity. Cold stress mediates a series of physiological and metabolite changes, such as alterations in chlorophyll fluorescence, electrolyte leakage, reactive oxygen species (ROS), malondialdehyde (MAD), sucrose, lipid peroxides, proline, and other metabolites, plant endogenous hormones abscisic acid (ABA) and gibberellin (GA) also changes. In this review, we summarize the recent research progress on physiological and metabolic changes under low temperature, cold stress related loci and QTL reported by map-based cloning and genome-wide association analysis (GWAS), and some molecular mechanisms in response to low temperature in rice. We also discuss the future prospects on breeding cold tolerance varieties of rice.

Effects of in vitro and in vivo avermectin exposure on alpha synuclein expression and proteasomal activity in pigeons.

Avermectins (AVMs) are used worldwide in agriculture and veterinary medicine. Residues of avermectin drugs, causing toxicological effects on non-target organisms, have raised great concern. The aim of this study was to investigate the effects of AVM on the expression levels of alpha synuclein (α-Syn) and proteasomal activity in pigeon (Columba livia) neurons both in vivo and in vitro. The results showed that, the mRNA and protein levels of α-Syn increased in AVM treated groups relative to control groups in the cerebrum, cerebellum and optic lobe in vivo. Dose-dependent decreases in the proteasomal activity (i.e., chymotrypsin-like, trypsin-like and peptidylglutamyl peptidehydrolase) were observed both in vivo and in vitro. The results suggested that AVM could induce the expression levels of α-Syn and inhibit the normal physiological function of proteasome in brain tissues and neurons. The information presented in this study is helpful to understand the mechanism of AVM-induced neurotoxicology in birds.

Avermectin induced global DNA hypomethylation and over-expression of heat shock proteins in cardiac tissues of pigeon.

Despite increasing evidences pointing to residues of avermectin (AVM) pose toxic effects on non-target organisms in environment, but the data in pigeon is insufficient. The alteration of global DNA methylation and response of heat shock proteins (Hsps) are important for assessing the AVM toxicity in cardiac tissues of pigeon (Columba livia). To investigate the effects of AVM exposure in cardiac tissues of pigeon, we detected the expression levels of DNA methyltransferases (Dnmts), methylated DNA-binding domain protein 2 (MBD2), and Hsp 60, 70 and 90. Pigeons were exposed to feed containing AVM (0, 20, 40 and 60mg/kg diet) for 30, 60, 90days respectively, and cardiac tissues were collected and analyzed. We found the transcriptional levels of Dnmt1, Dnmt3a and Dnmt3b mRNA were down-regulated, but the transcriptional levels of MBD2 mRNA were up-regulated by AVM exposure in cardiac tissues of pigeon. Necrocytosis, hemorrhage, infiltration of inflammatory cells and abundant vacuoles appeared in cardiac tissues after AVM exposure. Accompanying this phenotype, the mRNA transcriptional and/or protein levels of Hsp30, Hsp60, Hsp70 and Hsp90 increased. In conclusion, these results underscored AVM exposure caused DNA methylation machinery malfunctions, and induced over-expression of Hsps to improve the protective function against cardiac injury.

Autophagy is upregulated in brain tissues of pigeons exposed to avermectin.

Avermectin (AVM) is used in agriculture and veterinary medicine for the prevention of parasitic diseases; AVM is the active component of some insecticidal and nematicidal products. Residues of AVM drugs or their metabolites in livestock feces have toxic effects on non-target aquatic and terrestrial organisms. In this study, changes in the levels of autophagy related genes and ultrastructure in pigeon brain tissues after subchronic exposure to AVM for 30, 60 and 90 d were investigated. The decrease in the mRNA levels of TORC1 and TORC2 and increase in the mRNA levels of LC3, Beclin 1, Dynein, ATG5 and ATG4B and the increase in the protein levels of LC3, Beclin 1 and Dynein in a dose- and time-dependent manner in the pigeon brain were observed. The number of autophagic vacuoles in the cerebrum, cerebellum and optic lobe increased significantly with the concentration of AVM and the exposure time. We found that the changes in the levels of autophagy related genes and the ultrastructure in the cerebrum were more obvious than in the cerebellum and the optic lobe. The results suggest that AVM could induce autophagy in pigeon brain tissues. The information presented in this study is helpful for understanding the mechanism of AVM-induced autophagy in birds.

The effects of avermectin on amino acid neurotransmitters and their receptors in the pigeon brain.

The objective of this study was to examine the effects of avermectin (AVM) on amino acid neurotransmitters and their receptors in the pigeon brain. Four groups two-month-old American king pigeons (n=20/group) were fed either a commercial diet or an AVM-supplemented diet (20mg/kg·diet, 40 mg/kg·diet, or 60 mg/kg·diet) for 30, 60, or 90 days. The contents of aspartic acid (ASP), glutamate (GLU), glycine (GLY), and γ-aminobutyric acid (GABA) in the brain tissues were determined using ultraviolet high-performance liquid chromatography (HPLC). The expression levels of the GLU and GABA receptor genes were analyzed using real-time quantitative polymerase chain reaction (qPCR). The results indicate that AVM exposure significantly enhances the contents of GABA, GLY, GLU, and ASP in the cerebrum, cerebellum, and optic lobe. In addition, AVM exposure increases the mRNA expression levels of γ-aminobutyric acid type A receptor (GABAAR), γ-aminobutyric acid type B receptor (GABABR), N-methyl-d-aspartate 1 receptor (NR1), N-methyl-d-aspartate 2A receptor (NR2A), and N-methyl-d-aspartate 2B receptor (NR2B) in a dose- and time-dependent manner. Moreover, we found that the most damaged organ was the cerebrum, followed by the cerebellum, and then the optic lobe. These results show that the AVM-induced neurotoxicity may be associated with its effects on amino acid neurotransmitters and their receptors. The information presented in this study will help supplement the available data for future AVM toxicity studies.

Avermectin induced liver injury in pigeon: mechanisms of apoptosis and oxidative stress.

Extensive use of avermectin (AVM) can result in environment pollution, and it is important to evaluate the potential impact this antibiotic has on ecological systems. Few published literatures have discussed the liver injury mechanisms induced by AVM on birds. In this study, pigeons were exposed to feed containing AVM (0, 20, 40 and 60 mg/kg diet) for 30, 60, 90 days respectively. The results showed that AVM increased the number of apoptosis and the expression level of caspase-3, 8, fas mRNA in the liver of pigeons. Ultrastructural alterations, including mitochondrial damage and chromatin aggregation, become severe with increase exposure dose. Exposure to AVM induced significant changes in antioxidant enzyme {superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px)} activities and malondialdehyde (MDA) content, augmented protein carbonyl (PCO) content and DNA-protein crosslink (DPC) coefficient, in a concentration-dependent manner in the liver of pigeons. Our results show that AVM has toxic effect in pigeon liver, and the mechanism of injury caused by AVM is closely related to apoptosis and oxidative stress.

Effect of atrazine and chlorpyrifos exposure on cytochrome P450 contents and enzyme activities in common carp gills.

Chlorpyrifos (CPF) and atrazine (ATR) are the most widely used organophosphate insecticides and triazine herbicides, respectively, worldwide. This study aimed at investigating the effects of ATR, CPF and mixture on common carp gills following 40-d exposure and 40-d recovery experiments. Cytochrome P450 content, activities of aminopyrine N-demethylase (APND) and erythromycin N-demethylase (ERND) and the mRNA levels of the CYP1 family (CYP1A, CYP1B, and CYP1C) were determined. In total, 220 common carps were divided into eleven groups, and each group was treated with a specific concentration of ATR (4.28, 42.8 and 428 µg/L), CPF (1.16, 11.6 and 116 µg/L) or ATR-CPF mixture (1.13, 11.3 and 113 µg/L). The results showed that P450 content and activities of APND and ERND in fish exposed to ATR and mixture were significantly higher than those in the control group. After the 40-d recovery treatment (i.e., depuration), the P450 content and the activities of APND and ERND in fish decreased to the background levels. A similar tendency was also found in the mRNA levels of the CYP1 family (CYP1A, CYP1B, and CYP1C) in common carp gills. The CPF-treated fish showed no significant difference from the control groups, except for a significant CYP1C induction. These results indicated that CYP enzyme levels are induced by ATR but were only slightly affected by CPF in common carp gills. In addition, the ATR and CPF exposure showed an antagonistic effect on P450 enzymes in common carp gills.

Antioxidant response and histopathological changes in brain tissue of pigeon exposed to avermectin.

Avermectins (AVMs) are the active components of some insecticidal and nematicidal products used in agriculture and veterinary medicine for the prevention of parasitic diseases. Residues of AVM drugs or their metabolites in livestock feces have toxic effects on non-target aquatic and terrestrial organisms. In this study, oxidative stress responses and pathological changes on pigeon brain tissues and serum after subchronic exposure to AVM for 30, 60 and 90 days were investigated. The decrease in antioxidant enzyme (superoxide dismutase, SOD and glutathione peroxidase, GSH-Px) activities and increase in methane dicarboxylic aldehyde content in a dose-time-dependent manner in the brain and serum of pigeon were observed. The protein carbonyl content, an indicator of protein oxidation, and DNA-protein crosslink coefficient were significantly augmented with dose-time-dependent properties. The microscopic structures of the cerebrum, cerebellum and optic lobe altered obviously, the severity of which increased with the concentration of AVM and exposure time. The results imply that AVM could induce oxidative damage to the brain tissue and serum of pigeon. The information presented in this study is helpful to understand the mechanism of AVM-induced oxidative stress in birds.

[Effect of modified sijunzi decoction on the bone metabolism of adriamycin induced nephropathy rats].

OBJECTIVE: To explore the effect of Modified Sijunzi Decoction (MSD) on the bone metabolism of prednisone intervened adriamycin-induced nephropathy rats. METHODS: The adriamycin-induced nephropathy rat model was prepared. Totally 50 SD rats were randomly divide into five groups, i.e., the model group, the hormone group, the Chinese medicine (CM) group, the CM + hormone group, and the normal control group. The 24-h urine samples were collected on the 7th, 21st, and 35th day after modeling. The 24-h urine protein was measured by biuret colorimetry. Serum levels of osteoprotegerin (OPG), receptor activator of nuclear factor-kappaB ligand (RANKL), osteocalcin (BGP), and tartrate-resistant acid phosphatase (TRACP) were determined by ELISA. Expressions of OPG and RANKL in the tibia tissue were detected using real-time quantitative PCR and Western blot. RESULTS: (1) Compared with the normal control group, the 24-h urine protein increased in each group on the 7th, 21st, and 35th day (P < 0.05, P < 0.01). Compared with the model group, the 24-h urinary protein decreased in the hormone group and the CM + hormone group (P < 0.05, P < 0.01). The decrement was more obvious along with the treatment time went by (P < 0.05, P < 0.01). There was statistical difference in the reduction of urine protein on the 35th day between the CM group and the model group (P < 0.05). (2) Compared with the 21st-day of the same group, the serum levels of TRACP and RANKL increased (P < 0.05, P < 0.01). Compared with the model group, the serum levels of the TRACP and RANKL increased (P < 0.05, P < 0.01), OPG and BGP decreased (P < 0.05, P < 0.01) in the hormone group. Compared with the CM group at the same period, serum OPG level decreased and the RANKL level increased in the hormone group and the CM + hormone group (P < 0.05, P < 0.01). Besides, the serum level of TRACP increased and BGP decreased (P < 0.05, P < 0.01). Compared with the hormone group at the same period, OPG and BGP increased (P < 0.05, P < 0.01), RANKL decreased (P < 0.01) in the CM + hormone group. On the 35th day TRACP decreased (P < 0.01). (3) Compared with the normal group, mRNA expressions of OPG and RANKL on the 21st day increased (P < 0.05, P < 0.01), mRNA expressions of OPG and RANKL on the 35th day decreased in the model group (P < 0.01). Compared with the CM group at the same period, OPG mRNA expression decreased (P < 0.01) and RANKL mRNA expression increased in the hormone group (P < 0.05). OPG mRNA expression decreased in the CM +hormone group (P < 0.05). (4) Compared with the hormone group on the 21st day, the OPG level decreased and the RANKL protein increased (both P < 0.05). RANKL decreased in the CM + hormone group (P < 0.05). Compared with the model group at the same period, OPG decreased and RANKL increased in the hormone group (P < 0.01). Compared with the CM group at the same period, OPG decreased (P < 0.01), RANKL increased (P < 0.01) in the hormone group and the CM + hormone group. Compared with the hormone group at the same period, OPG increased and RANKL decreased in the CM + hormone group (both P < 0.01). CONCLUSIONS: Prednisone could induce osteoporosis through the OPG/RANKL/RANK pathway. MSZ could slow down the formation of prednisone-induced osteoporosis through promoting osteoblast differentiation, and inhibiting osteoclastogenesis.

Selenium regulates Nrf2 signaling to prevent hepatotoxicity induced by hexavalent chromium in broilers.

Hexavalent chromium (Cr(Ⅵ)) is considered to be a common environmental pollutant, which widely exists in industrial effluents and wastes and then potentially noxious effects to the health of the poultry. Studies have reported that selenium (Se), which is one of the essential trace elements of the poultry and participates in the oxidative metabolism, can alleviate Cr(Ⅵ)-induced organ damage by inhibiting oxidative stress, but its specific molecular mechanism remains unclear. Herein, animal models of Cr(Ⅵ)- and Se-exposure were constructed using broilers to investigate the antagonistic mechanism of Se to Cr(Ⅵ)-induced hepatotoxicity. In this experiment, the four groups of broiler models were used as the research objects: control, Se, Se plus Cr, and Cr groups. Histopathology and ultrastructure liver changes were observed. Liver-somatic index, serum biochemistry, oxidative stress, Nrf2 pathway related factors, and autophagy-related genes were also determined. Overall, Se was found to ameliorate the disorganized structure, hepatic insufficiency, and oxidative damage caused by Cr(Ⅵ) exposure. Electron microscopy analysis further showed that the number of autophagosomes was obviously decreased after Se treatment compared to Cr group. Furthermore, gene and protein expression analyses illustrated that the levels of Nrf2, glutathione peroxidase 1 (GPx-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), and mechanistic target of rapamycin (mTOR) in the Se&Cr group was upregulated, along with decreased expression of Beclin 1, ATG5 and LC3 compared to the Cr group. These suggest that Se can repair the oxidative lesion and autophagy induced by Cr(Ⅵ) exposure in broiler livers by upregulating the Nrf2 signaling pathway.

Evaluation of Liquid Organic Acids on the Performance, Chyme pH, Nutrient Utilization, and Gut Microbiota in Broilers under High Stocking Density.

This study aimed to evaluate the efficacy of organic acids (OAs) in starter broilers and to investigate whether supplemental OAs could alleviate the high stocking density (HSD) stress condition in grower broilers. A total of 408 1-day-old Arbor Acres broilers were assigned into two groups without or with liquid OAs in the starter phase. In the grower phase, each group in the starter phase was divided into a normal stocking density and an HSD. The OA dose was 0.16% at the starter and grower phases. The results showed that at the starter phase, OAs decreased the chyme pH in gizzard and duodenum and increased the activities of chymotrypsin and α-amylase in the duodenal chyme (p < 0.05). In the grower phase, an HSD decreased the growth performance and the ether extract digestibility (p < 0.01). The supplementation of OAs decreased the chyme pH in the gizzard, proventriculus, and duodenum and increased the lipase and α-amylase activities (p < 0.05). The supplemental OAs increased the dry matter and total phosphorous digestibility and the contents of acetic acids, butyric acids, isovaleric acids, and valeric acids (p < 0.05). For cecal microbial compositions at the genus level, an HSD decreased the relative abundance of Blautia, Norank_f__norank_o__RF39, and Alistipes, while supplemental OAs increased the relative abundance of Norank_f__norank_o__RF39 (p < 0.05). In conclusion, although there were no interaction effects between OAs and stocking densities in the present study, it was clear that the supplementation of OAs has beneficial effects on the chyme pH, enzymes activities, and nutrient digestibility in broilers, while an HSD existed adverse effects on the growth performance, nutrient digestibility, and gut microbiota balance in grower broilers.

OsPMS1 Mutation Enhances Salt Tolerance by Suppressing ROS Accumulation, Maintaining Na+/K+ Homeostasis, and Promoting ABA Biosynthesis.

World-wide, rice (Oryza sativa L.) is an important food source, and its production is often adversely affected by salinity. Therefore, to ensure stable rice yields for global food security, it is necessary to understand the salt tolerance mechanism of rice. The present study focused on the expression pattern of the rice mismatch repair gene post-meiotic segregation 1 (OsPMS1), studied the physiological properties and performed transcriptome analysis of ospms1 mutant seedlings in response to salt stress. Under normal conditions, the wild-type and ospms1 mutant seedlings showed no significant differences in growth and physiological indexes. However, after exposure to salt stress, compared with wild-type seedlings, the ospms1 mutant seedlings exhibited increased relative water content, relative chlorophyll content, superoxide dismutase (SOD) activity, K+ and abscisic acid (ABA) content, and decreased malondialdehyde (MDA) content, Na+ content, and Na+/K+ ratio, as well as decreased superoxide anion (O2-) and hydrogen peroxide (H2O2) accumulation. Gene ontology (GO) analysis of the differentially expressed genes (DEGs) of ospms1 mutant seedlings treated with 0 mM and 150 mM NaCl showed significant enrichment in biological and cytological processes, such as peroxidase activity and ribosomes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis showed that the DEGs specifically enriched ascorbate and aldarate metabolism, flavone and flavonol biosynthesis, and glutathione metabolism pathways. Further quantitative real-time reverse transcription-PCR (qRT-PCR) analysis revealed significant changes in the transcription levels of genes related to abscisic acid signaling (OsbZIP23, OsSAPK6, OsNCED4, OsbZIP66), reactive oxygen scavenging (OsTZF1, OsDHAR1, SIT1), ion transport (OsHAK5), and osmoregulation (OsLEA3-2). Thus, the study's findings suggest that the ospms1 mutant tolerates salt stress at the seedling stage by inhibiting the accumulation of reactive oxygen species, maintaining Na+ and K+ homeostasis, and promoting ABA biosynthesis.

Selenium-Enriched Yeast Relieves Hexavalent Chromium Toxicity by Inhibiting NF-κB Signaling Pathway in Broiler Spleens.

This study was conducted to investigate the molecular mechanisms of selenium (Se) antagonism of hexavalent chromium (Cr6+)-induced toxicity. Potassium dichromate (K2Cr2O7) and selenium-enriched yeast (SeY) were used to construct the single Cr6+ and combined Se/Cr6+ exposure broiler models, and then the broilers were randomly divided into four groups (C group, Se group, Se/Cr6+ group, and Cr6+ group). After a 42-day experiment, the spleen tissues of broilers were excised and weighted. The antagonistic mechanisms of Se and Cr6+ were evaluated using histopathological assessment, serum biochemical tests, oxidative stress kits, ELISA, qPCR, and Western blotting. On the whole, there were no significant changes between the C and Se groups. The spleen organ index in the Cr6+ group was significantly decreased, but SeY increased spleen organ index to a certain extent. The levels of SOD and GSH were reduced, and the MDA content was elevated by Cr6+; however, these changes were mitigated by Se/Cr6+ exposure. Importantly, Cr6+ exposure induced a series of histopathological injuries in broiler spleen tissues, while these symptoms were significantly relieved in the Se/Cr6+group. Furthermore, Cr6+ significantly decreased the levels of T-globulin, IgA, IgM, and IgG in serum. Contrarily, dramatically more T-globulin IgA, IgM, and IgG were found in the Se/Cr6+group than in the Cr6+ group. Revealed by the results of qPCR and WB, the expressions of NF-κB, IκBα, and p-IκBα were upregulated in Cr6+ groups, while they were downregulated in Se/Cr6+ group compared to that in Cr6+ group. Besides IFN-γ and IL-2, the expressions of pro-inflammatory cytokines were significantly increased by Cr6+ exposure, but the SeY supplement relived the expression levels mediated by Cr6+ exposure. In conclusion, our findings suggest SeY has biological activity that can protect broiler spleens from immunosuppression and inflammation induced by Cr6+, and we speculate that the NF-κB signaling pathway is one of its mechanisms.

Low Level of Dietary Organic Trace Minerals Improved Egg Quality and Modulated the Status of Eggshell Gland and Intestinal Microflora of Laying Hens During the Late Production Stage.

This study aimed to investigate the effects of dietary organic trace minerals on egg quality and intestinal microflora of laying hens during the late production stage. In total, 1,080 Jinghong-1 laying hens aged 57 weeks were randomly assigned to five treatment groups: CON, basal diet containing about 6, 29, 49, and 308 mg·kg-1 of Cu, Mn, Zn, and Fe; IT100, basal diet supplemented with 10, 80, 80, and 60 mg·kg-1 of Cu, Mn, Zn, and Fe (each as inorganic sulfates), respectively; OT20, basal diet supplemented with 2, 16, 16, and 12 mg·kg-1 of Cu, Mn, Zn, and Fe (each as organic trace minerals chelated with lysine and methionine in the ratio of 2:1 amino acid: organic trace minerals), respectively; OT30, basal diet supplemented with 3, 24, 24, and 18 mg·kg-1 of organic Cu, Mn, Zn, and Fe, respectively; and OT50, basal diet supplemented with 5, 40, 40, and 30 mg·kg-1 of organic Cu, Mn, Zn, and Fe, respectively. Overall, OT20, OT30, and OT50 had equal or higher potential to promote Cu, Mn, Zn, and Fe deposition in egg yolks compared with IT100. In addition, OT50 enhanced the eggshell breaking strength and the antioxidant status of the eggshell gland. Cecal microbiota, including Barnesiellaceae and Clostridia, were significantly decreased in IT100- and OT50-treated hens compared with the CON group. Clostridia UCG-014 was negatively correlated with eggshell weight and OCX-32. In conclusion, reduced supplementation of organic trace minerals can improve the eggshell quality and trace mineral deposition, possibly by modulating genes involved in the eggshell formation in the eggshell gland and by controling of the potentially harmful bacteria Barnesiellaceae and Clostridiales in the cecum. Inorganic trace minerals may be effectively replaced by low level of complex organic trace minerals in laying hens during the late production stage.