Novel compound heterozygous variants in FANCI cause premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a common reproductive aging disorder due to a dramatic decline of ovarian function before 40 years of age. Accumulating evidence reveals that genetic defects, particularly those related to DNA damage response, are a crucial contributing factor to POI. We have demonstrated that the functional Fanconi anemia (FA) pathway maintains the rapid proliferation of primordial germ cells to establish a sufficient reproductive reserve by counteracting replication stress, but the clinical implications of this function in human ovarian function remain to be established. Here, we screened the FANCI gene, which encodes a key component for FA pathway activation, in our whole-exome sequencing database of 1030 patients with idiopathic POI, and identified two pairs of novel compound heterozygous variants, c.[97C > T];[1865C > T] and c.[158-2A > G];[c.959A > G], in two POI patients, respectively. The missense variants did not alter FANCI protein expression and nuclear localization, apart from the variant c.158-2A > G causing abnormal splicing and leading to a truncated mutant p.(S54Pfs*5). Furthermore, the four variants all diminished FANCD2 ubiquitination levels and increased DNA damage under replication stress, suggesting that the FANCI variants impaired FA pathway activation and replication stress response. This study first links replication stress response defects with the pathogenesis of human POI, providing a new insight into the essential roles of the FA genes in ovarian function.

Deciphering the DNA methylome in women with PCOS diagnosed using the new international evidence-based guidelines.

STUDY QUESTION: Is there any methylome alteration in women with PCOS who were diagnosed using the new international evidence-based guidelines? SUMMARY ANSWER: A total of 264 differentially methylated probes (DMPs) and 53 differentially methylated regions (DMRs) were identified in patients with PCOS and healthy controls. WHAT IS KNOWN ALREADY: PCOS is a common endocrine disorder among women of reproductive age and polycystic ovarian morphology (PCOM) is one of the main features of the disease. Owing to the availability of more sensitive ultrasound machines, the traditional diagnosis of PCOM according to the Rotterdam criteria (≥12 antral follicles per ovary) is currently debated as there is a risk of overdiagnosis. The new international evidence-based guidelines set the threshold for PCOM as ≥20 antral follicles per ovary when using endovaginal ultrasound transducers with a frequency bandwidth that includes 8 MHz. However, current DNA methylation studies in PCOS are still based on the Rotterdam criteria. This study aimed to explore aberrant DNA methylation in patients diagnosed with PCOS according to the new evidence-based guidelines. STUDY DESIGN, SIZE, DURATION: This cross-sectional case-control study included 34 PCOS cases diagnosed using new international evidence-based guidelines and 36 controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 70 women, including 34 PCOS cases and 36 controls, were recruited. DNA extracted from whole blood samples of participants were profiled using array technology. Data quality control, preprocessing, annotation, and statistical analyses were performed. Least absolute shrinkage and selection operator (LASSO) regression were used to build a PCOS diagnosis model with DNA methylation sites. MAIN RESULTS AND THE ROLE OF CHANCE: We identified 264 DMPs between PCOS cases and controls, which were mainly located in intergenic regions or gene bodies of the genome, CpG open sea sites, and heterochromatin of functional elements. Pathway enrichment analysis showed that DMPs were significantly enriched in biological processes involved in triglyceride regulation. Three of these DMPs overlapped with the PCOS susceptibility genes thyroid adenoma-associated protein (THADA), aminopeptidase O (AOPEP), and tripartite motif family-like protein 2 (TRIML2). Fifty-three DMRs were identified and their annotated genes were largely enriched in allograft rejection, thyroid hormone production, and peripheral downstream signaling effects. Two DMRs were closely related to the PCOS susceptibility genes, potassium voltage-gated channel subfamily A member 4 (KCNA4) and farnesyl-diphosphate farnesyltransferase 1 (FDFT1). Finally, based on LASSO regression, we built a methylation marker model with high accuracy for PCOS diagnosis (AUC=0.952). LIMITATIONS, REASONS FOR CAUTION: The study cohort was single-center and the sample size was relatively limited. Further analyses with a larger number of participants are required. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study to identify DNA methylation alterations in women with PCOS diagnosed using the new international evidence-based guideline, and it provided new molecular insight into the application of the new guidelines. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2021YFC2700400), Basic Science Center Program of NSFC (31988101), CAMS Innovation Fund for Medical Sciences (2021-I2M-5-001), National Natural Science Foundation of China (32370916, 82071606, 82101707, 82192874, and 31871509), Shandong Provincial Key Research and Development Program (2020ZLYS02), Taishan Scholars Program of Shandong Province (ts20190988), and Fundamental Research Funds of Shandong University. The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

The extracellular polysaccharide inhibit porcine epidemic diarrhea virus with extract and gene editing Lacticaseibacillus.

Lacticaseibacillus is one of the predominant microorganisms in gut from human and animal, and the lacticaseibacillus have effective applications against the viral diarrhea of piglets in the farm. However, the function and the concrete cell single pathways of the active ingredient from lacticaseibacillus was not clear within anti-infection in the postbiotics research. Here, we compared the biological function of extracellular polysaccharides (EPS) purified from lacticaseibacillus casei (L. casei) and gene editing lacticaseibacillus casei with the CRISPER-Cas9 technology, which were with the ability of antioxidation and anti-inflammation, and the EPS could also inhibit the ROS production within the Porcine Small Intestinal Epithelial Cells-J2 (IPEC-J2). Interestingly, we found that both of EPS and genome editing lacticaseibacillus casei could specifically target the IFN-λ expression in the IPEC-J2, which was beneficial against the PEDV infection in the virus replication and production with the qRT-PCR and indirect immunofluorescence methods. Finally, the STAT3 cell single pathway was stimulated to transcribe IFN-λ with the EPS to elucidate the detailed mechanism of activating type III IFN signals receptor of IL-10R2, which play the function between anti-inflammation and anti-virus in the PEDV infection. Taken together, our research linked a postbiotics of EPS with the antiviral infection of PEDV, which suggest that the lacticaseibacillus itself still have displayed the potential immunomodulatory activities, and highlight the immunomodulatory potential of EPS-producing microbes.

High Retention Immobilization of Iodine in B-Bi-Zn Oxide Glass Using Bi2O3 as a Stabilizer under a N2 Atmosphere.

The immobilization of iodine waste suffers from serious iodine loss during heat treatment. Herein, we reported on the high iodine retention immobilization of simulated radioiodine-contaminated Bi0-SiO2 sorbent in B-Bi-Zn oxide glass using Bi2O3 as a stabilizer under a N2 atmosphere. The effects of the Bi2O3 content and sintering atmosphere on the iodine immobilization behaviors (iodine retention ratio, phase composition, microstructure, and chemical stability) were investigated. It was found that the decomposition of BiI3 was prevented by adding Bi2O3 and sintering in a N2 atmosphere. The iodine retention ratio in the obtained glass waste form was significantly enhanced with increasing Bi2O3 content and sintering in the N2 atmosphere due to the synergistic effect. The achieved record-high iodine retention (92.22 ± 2.6%) was much higher than that of conventional heat treatment route (18.01 ± 3.5%). The results demonstrated that iodine was effectively immobilized through the formation of stable BixOyI (Bi5O7I and BiOI). Furthermore, the obtained iodine waste form exhibited excellent compactness and chemical stability. Owing to its high iodine retention ratio, this route can be employed to effectively immobilize radioactive iodine.

Stress response of ABI5 to BR stress and its regulation on hypocotyls growth in Arabidopsis thaliana.

Abscisic acid-insensitive 5 (ABI5) is a basic leucine zipper (bZIP) transcription factor that is abundantly expressed in seeds. It plays a central role in regulating the abscisic acid (ABA) signal of seed germination and early seedling growth. Brassinosteroid (BR) is a new type of plant endogenous hormone, which has many physiological functions such as regulating plant growth and development and response to adversity stress. It has recently been discovered that under brassinolide stress, BIN2 (BRASSINOSTEROID INSENSITIVE2) and BES1 (BRI1-EMS-SUPPRESSOR 1) in the BR signaling pathway can inhibit the expression of ABI5 and promote Arabidopsis thaliana seed germination. In order to further explore the function of ABI5 under BR stress, this study analyzed the ABI5 expression characteristics during seed germination, identified Arabidopsis ABI5 gene deletion mutant abi5-1 and analyzed its function under BR stress, the results of which indicated that ABI5 was abundantly expressed in Arabidopsis dry seeds and responded to BR stress during germination. Under normal conditions, there was no significant difference between the hypocotyls of abi5-1 and wild-type seedlings; but under BR stress, the hypocotyls of abi5-1 seedlings were significantly longer than those of wild-type seedlings. These results reveal that ABI5 regulates the growth of Arabidopsis hypocotyls under BR stress, thereby providing a basis for in-depth understanding of the molecular mechanism of ABI5 regulation on plant development.

Targeting peptide-enhanced antibody and CD11c+ dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice.

Enterotoxigenic Escherichia coli (ETEC) remains a massive burden in developing countries with increasing morbidity and mortality rates; it is also an important pathogen in the farming industry and is a leading cause of bacterial diarrhea. Our previous study showed that nanometer-sized inclusion bodies (IBs) of the fimbrial adhesin subunit protein (FaeG), mutation heat-stable enterotoxin a (mSTa), heat-labile enterotoxin b (LTb), and STb (nontargeting) fusion protein as an oral vaccine induced both systemic and mucosal immune responses. In this study, to enhance the protective efficacy to ETEC, we used Yersinia enterocolitica adhesive and M-cell-targeting peptides to analyze high-efficiency antigen-specific immune presentation in the gut. Here, we showed that immunization with the IBs of ETEC-FaeG-mSTa-LTb-STb-induced a specific systemic and mucosal immune response in the gut, whereas the combination of both targeting peptides resulted in the highest titer, protective immune response against ETEC. A lymphocyte proliferation assay has shown that the IBs induced immunologic memory. The specific antibody of the targeting groups could effectively neutralize toxins, thereby protecting the cells of the small intestine and reducing the level of cAMP and cGMP, and the groups with double targeting showed the best effect. The most important finding was that the targeting peptides stimulate the T helper (Th) cells through Th17 and Th1 and that Th1 cells dominated the cellular immune response. We found that the targeting peptide could also activate CD11c+ on lymphoid dendritic cells, which processed and presented antigens to T cells through Th1-mediated IFN-γ and IL-12, thereby enhancing the antibody titers. The double-targeting peptide had a better effect on stimulating the immune cells to enhance the antibody titers.-Jiang, X., Xia, S., He, X., Ma, H., Feng, Y., Liu, Z., Wang, W., Tian, M., Chen, H., Peng, F., Wang, L., Zhao, P., Ge, J., Liu, D. Targeting peptide-enhanced antibody and CD11c+ dendritic cells to inclusion bodies expressing protective antigen against ETEC in mice.

Manganese dioxide-loaded mesoporous SBA-15 silica composites for effective removal of strontium from aqueous solution.

Manganese dioxide-loaded mesoporous SBA-15 silica (MnO2/SBA-15) composites with short pore length were aprepared for the first time by simply immersing SBA-15 into a KMnO4 and MnCl2 mixed solution. Adsorption of Sr2+ from aqueous solution by using the MnO2/SBA-15 was investigated by varying the pH, contact time, initial Sr2+ concentration, MnO2 content and temperature. The adsorption process was rapid during the first 40 min and reached equilibrium in 120 min. The Sr2+ adsorption capacity increased with increasing pH, MnO2 content and temperature, and the adsorption capacity of SBA-15 was significantly improved by the loading of MnO2. Moreover, the experimental adsorption data were analyzed using different equilibrium isotherm, kinetic and thermodynamic models. The results showed that the isotherm data were well-described by the Langmuir model. The maximum Sr2+ adsorption capacity was determined to be 75.1 mg g-1 at 283 K based on the Langmuir model. The analyzed kinetic data indicated that the Sr2+ adsorption process was well fitted by the pseudo-second order model. Furthermore, the thermodynamic parameters of adsorption were also determined from the equilibrium constant values obtained at different temperatures. The results suggested that the adsorption process was spontaneous and endothermic, and the overall mechanism of Sr2+ adsorption was a combination of physical and chemical processes.

Transcriptomics Analysis on Excellent Meat Quality Traits of Skeletal Muscles of the Chinese Indigenous Min Pig Compared with the Large White Breed.

The Min pig (Sus scrofa) is a well-known indigenous breed in China. One of its main advantages over European breeds is its high meat quality. Additionally, different cuts of pig also show some different traits of meat quality. To explore the underlying mechanism responsible for the differences of meat quality between different breeds or cuts, the longissimus dorsi muscle (LM) and the biceps femoris muscle (BF) from Min and Large White pigs were investigated using transcriptome analysis. The gene expression profiling identified 1371 differentially expressed genes (DEGs) between LM muscles from Min and Large White pigs, and 114 DEGs between LM and BF muscles from the same Min pigs. Gene Ontology (GO) enrichment of biological functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that the gene products were mainly involved in the IRS1/Akt/FoxO1 signaling pathway, adenosine 5'-monophosphate-activated protein kinase (AMPK) cascade effects, lipid metabolism and amino acid metabolism pathway. Such pathways contributed to fatty acid metabolism, intramuscular fat deposition, and skeletal muscle growth in Min pig. These results give an insight into the mechanisms underlying the formation of skeletal muscle and provide candidate genes for improving meat quality. It will contribute to improving meat quality of pigs through molecular breeding.

Identification of Candidate Genes for Min Pig Villi Hair Traits by Genome-Wide Association of Copy Number Variation.

The Min pig is a famous native pig breed in northeast China, which has the special genetic character of villi hair growth in cold seasons. At present, little research has focused on the genetic mechanism of villi hair growth in Min pigs. Copy number variations (CNVs) are a type of variant that may influence many traits. In this study, we first investigated the phenotype of Large White × Min pigs' F2 pig villi hair in detail and then performed a CNV-based genome-wide association study (GWAS) between CNVs and pig villi hair appearance. Finally, a total number of 15 significant CNVRs were found to be associated with Min pig villi hair. The most significant CNVR was located on chromosome 1. Nearest gene annotation analysis indicated that the pig villi hair traits may be associated with the biological process of the G-protein-coupled receptor signaling pathway. QTL overlapping analysis found that among the CNVRs, 14 CNVRs could be co-located with known QTLs. Some genes such as MCHR2, LTBP2, and GFRA2 may be candidate genes for pig villi traits and are worth further study. Our study may provide a basic reference for the selection and breeding of cold-resistant pigs and outdoor breeding.

Crosstalk between trace elements and T-cell immunity during early-life health in pigs.

With gradual ban on the use of antibiotics, the deficiency and excessive use of trace elements in intestinal health is gaining attention. In mammals, trace elements are essential for the development of the immune system, specifically T-cell proliferation, and differentiation. However, there remain significant gaps in our understanding of the effects of certain trace elements on T-cell immune phenotypes and functions in pigs. In this review, we summarize the specificity, development, subpopulations, and responses to pathogens of porcine T cells and the effects of functional trace elements (e.g., iron, copper, zinc, and selenium) on intestinal T-cell immunity during early-life health in pigs. Furthermore, we discuss the current trends of research on the crosstalk mechanisms between trace elements and T-cell immunity. The present review expands our knowledge of the association between trace elements and T-cell immunity and provides an opportunity to utilize the metabolism of trace elements as a target to treat various diseases.

Characterization of Growth Secondary Hair in Min Pig Activated by Follicle Stem Cell Stimulated by Wnt and BMP Signaling Pathway.

In China, the national-level protected pig, the Min pig, is characterized by the development of secondary hairs and hair follicles in winter. Factors that dominate the genotype in the growth of secondary hairs are not clear through the concrete cell signaling pathways. This study compared hair phenotypes based on morphological structure, transcriptomics, and potential targeting molecules in the breeds of Min, Berkshire, and Yorkshire pigs. The results indicated that Min pigs have specific characteristics for the growth of secondary hairs compared with the Berkshire and Yorkshire pigs. The transcriptome analyses and quantitative reverse transcription-polymerase chain reaction results revealed that secondary hair growth was activated by follicle stem cells. The specific inhibitors of Wnt and BMP were studied using respective signals. The density of follicles, activity of follicle stem cells, and relative gene expression results have shown that Wnt and BMP stimulate the activity of follicle stem cells, and the Wnt signaling molecule has a significantly better effect than the BMP signaling molecule on stem cells. Wnt and BMP can promote the growth of local secondary hair and gene expression. Therefore, this study was conducted to verify the development mechanisms of secondary hairs, which have potential applications in laboratory animals and comparative medicine.

The Oral Inactivated Porcine Epidemic Diarrhea Virus Presenting in the Intestine Induces Mucosal Immunity in Mice with Alginate-Chitosan Microcapsules.

The porcine epidemic diarrhea virus, PEDV, which causes diarrhea, vomiting and death in piglets, causes huge economic losses. Therefore, understanding how to induce mucosal immune responses in piglets is essential in the mechanism and application against PEDV infection with mucosal immunity. A method of treatment in our research was used to make an oral vaccine that packaged the inactive PEDV with microencapsulation, which consisted of sodium alginate and chitosan, and adapted the condition of the gut in mice. The in vitro release experiment of microcapsules showed that inactive PEDV was not only easily released in saline and acid solutions but also had an excellent storage tolerance, and was suitable for use as an oral vaccine. Interestingly, both experimental groups with different doses of inactive virus enhanced the secretion of specific antibodies in the serum and intestinal mucus, which caused the effective neutralization against PEDV in the Vero cell by both IgG and IgA, respectively. Moreover, the microencapsulation could stimulate the differentiation of CD11b+ and CD11c+ dendritic cells, which means that the microencapsulation was also identified as an oral adjuvant to help phagocytosis of dendritic cells in mice. Flow cytometry revealed that the B220+ and CD23+ of the B cells could significantly increase antibody production with the stimulation from the antigens' PEDV groups, and the microencapsulation could also increase the cell viability of B cells, stimulating the secretion of antibodies such as IgG and IgA in mice. In addition, the microencapsulation promoted the expression of anti-inflammatory cytokines, such as IL-10 and TGF-ß. Moreover, proinflammatory cytokines, such as IL-1, TNF-α, and IL-17, were inhibited by alginate and chitosan in the microencapsulation groups compared with the inactivated PEDV group. Taken together, our results demonstrate that the microparticle could play the role of mucosal adjuvant, and release inactivated PEDV in the gut, which can effectively stimulate mucosal and systemic immune responses in mice.

Loss in the Antibacterial Ability of a PyrR Gene Regulating Pyrimidine Biosynthesis after Using CRISPR/Cas9-Mediated Knockout for Metabolic Engineering in Lactobacillus casei.

Lactobacillus casei (L. casei) has four possible mechanisms: antimicrobial antagonism, competitional adhesion, immunoregulation, and the inhibition of bacterial toxins. To delineate the metabolic reactions of nucleotides from L. casei that are associated with mechanisms of inhibiting pathogens and immunoregulation, we report that a PyrR-deficient L. casei strain was constructed using the CRISPR-Cas9D10A tool. Furthermore, there were some changes in its basic biological characterization, such as its growth curve, auxotroph, and morphological damage. The metabolic profiles of the supernatant between the PyrR-deficient and wild strains revealed the regulation of the synthesis of genetic material and of certain targeting pathways and metabolites. In addition, the characteristics of the PyrR-deficient strain were significantly altered as it lost the ability to inhibit the growth of pathogens. Moreover, we identified PyrR-regulating pyrimidine biosynthesis, which further improved its internalization and colocalization with macrophages. Evidence shows that the PyrR gene is a key active component in L. casei supernatants for the regulation of pyrimidine biosynthesis against a wide range of pathogens.

Mycotoxins in livestock feed in China - Current status and future challenges.

Mycotoxins are toxic metabolites or secondary metabolites produced by fungi and exist widely in all kinds of food and feed raw materials. They have led to many poisoning events and brought huge economic losses to livestock and poultry breeders every year. At present, the main challenges in the field of feed mycotoxin prevention and control are the high contamination rate, high coexistence rate, high detection cost and lagging research and development of prevention and control technology. Based on research data and results published by Chinese scholars in academic journals at home and abroad in recent years, this paper summarizes the status and causes of mycotoxin contamination in different feeds in China. At the same time, problems exist in the detection of mycotoxin contamination in Chinese feed. It is hoped to provide guidelines for the prevention and control of mycotoxin contamination.

Transcriptome Analysis Reveals Genes Contributed to Min Pig Villi Hair Follicle in Different Seasons.

The Min pig, a local pig breed in China, has a special trait which has intermittent villus and coat hair regeneration. However, the regulation and mechanism of villus in Min pigs have not yet been described. We observed and described the phenotype of Min pig dermal villi in detail and sequenced the mRNA transcriptome of Min pig hair follicles. A total of 1520 differentially expressed genes (DEG) were obtained.K-means hierarchical clustering showed that there was a significant expression pattern difference in winter compared with summer. Gene enrichment and network analysis results showed that the hair growth in Min pigs was closely related to the composition of desmosomes and regulated by an interaction network composed of eight core genes, namely DSP, DSC3, DSG4, PKP1, TGM1, KRT4, KRT15, and KRT84. Methylation analysis of promoters of target genes showed that the PKP1 gene was demethylated. Our study will help to supplement current knowledge of the growth mechanism of different types of hair.

Effects of residual monensin in livestock manure on nitrogen transformation and microbial community during "crop straw feeding-substrate fermentation-mushroom cultivation" recycling system.

Although crop-livestock integration recycling systems improve nitrogen (N) utilization in agroecosystems, there are limited studies regarding impacts of residual antibiotics in livestock manure on N transformation in entire recycling system. The objective was to evaluate effects of feeding monensin on N recycling during "straw feeding-substrate fermentation-mushroom cultivation". This experiment contained 3 steps. During straw feeding, beef cattle were allocated into 2 groups and fed diets with or without monensin, respectively. During fermentation, beef cattle manure (with or without monensin) and straw (corn or wheat) and were co-fermented for 35 d to produce substrates. During cultivation, Agaricus bisporus was cultivated on 4 substrates to recycle N in the form of mushrooms. Rates of N retention during fermentation were significant higher for monensin and corn straw treatments and there was an significant interaction between straw and antibiotic on N retention rate during cultivation. However, residual monensin significantly reduced amount of recycled N during entire recycling system, due to changes in N transformation-associated enzyme activity, ammonification and denitrification plus microbial community structure and succession. Specifically, residual monensin inhibited growth of dominant bacterial phylum Bacteroidetes and fungal phylum Neocallimastigomycota, and increased bacterial phylla Actinobacteriota and Firmicutes. These alterations in functional microbes increased N retention rates but reduced mushroom yields in antibiotic treatments during cultivation. In conclusion, monensin decreased the N recycling rate in recycling system, but also reduced N losses during fermentation by inhibiting ammonification and denitrification, so, avoiding antibiotics usage is an effective strategy to improve the efficiency of recycling systems.

Facile synthesis of novel Bi0-SBA-15 adsorbents by an improved impregnation reduction method for highly efficient capture of iodine gas.

Development of high efficient adsorbents to capture iodine is of great significance for the active development of nuclear power. Herein, Bi0-SBA-15 was firstly synthesized and applied for capture of iodine gas. Bi0-SBA-15 materials were prepared by an improved impregnation reduction method. The benefit of this method was that the Bi0 nanoparticles with flocculent and spherical morphologies were loaded on the surface of SBA-15, which provide abundant active sites for iodine and improve the utilization rate of active sites, so as to attain a record high capture capacity (up to 925 mg/g within 60 min) and high stablitiy (91.2%) at 200 °C. The results demonstrated that the loading of Bi0 on the surface showed a significant impact on the structure of Bi0-SBA-15 and did greatly enhance the iodine capture. Furthermore, the high iodine capture capacity mainly derived from the chemical adsorption in the stable form of BiI3. The obtained Bi0-SBA-15 materials exhibited excellent aqueous and irradiation stability. Thus, the results indicated that the new and highly efficient Bi0-SBA-15 was a potential radioactive iodine gas capture material.

Evaluation of dietary Perilla frutescens seed on performance and carcass quality in finishing castrated male Songliao black pigs.

OBJECTIVES: This study was conducted to investigate the effects of dietary supplementation of Perilla frutescens seed (PFS) on growth performance, blood profiles, meat quality and meat nutrient characteristics in finishing castrated male Songliao black pigs. METHODS: A total of 80 castrated male Songliao black pigs with an average initial body weight (BW) of 84.1 ± 2.1 kg were used in a 75 days feeding trial. All pigs were randomly assigned into four dietary treatments: CON, basal diet; PFS3.0, basal diet + 3.0% of PFS; PFS6.0, basal diet + 6.0% of PFS and PFS9.0, basal diet + 9.0% of PFS. RESULTS: As a result of this experiment, dietary supplementation of PFS improved the growth performance parameters, blood albumin and blood lipid parameters. Whereas, on FBW, average daily feed intake and average daily gain there showed a non-dose-dependent manner that pigs in PFS9.0 had lowest performance compared with other two PFS treatments. Furthermore, meat colour of yellowness, pH, cook meat rate, moisture, crude protein and crude fat were increased by PFS addition. However, lower growth performance was observed in PFS9.0 group. As well as, dietary inclusion of PFS also alters the meat amino acid composition and meat fatty acids composition. Particularly, umami amino acid contents and polyunsaturated fatty acid were all enhanced by PFS addition. CONCLUSIONS: In summary, dietary supplementation of PFS have beneficial effects on the performance and meat quality and nutritional values in Songliao black pigs.

Ferroptosis and Its Multifaceted Role in Cancer: Mechanisms and Therapeutic Approach.

Ferroptosis, a new type of non-apoptotic cell death modality, is different from other modes of cell death and has been primarily found in tumor cells. Previous studies have reported that ferroptosis can be triggered by specific modulators (e.g., drugs, nutrients, and iron chelators), leading to increased intracellular lipid reactive oxygen species (ROS) accumulation and iron overload. Recent reports have shown that ferroptosis at the cellular and organism levels can prevent an inflammatory storm and cancer development. Emerging evidence suggests potential mechanisms (e.g., system Xc-, glutathione peroxidase 4 (GPX4), lipid peroxidation, glutathione (GSH), and iron chelators) are involved in ferroptosis, which may mediate biological processes such as oxidative stress and iron overload to treat cancer. To date, there are at least three pathways that mediate ferroptosis in cancer cells: system Xc-/GSH/GPX4, FSP1/CoQ10/NAD(P)H, and ATG5/ATG7/NCOA4. Here, we summarize recent advances in the occurrence and development of ferroptosis in the context of cancer, the associations between ferroptosis and various modulators, and the potential mechanisms and therapeutic strategies targeting ferroptosis for the treatment of cancer.

Improvement of Ulcerative Colitis by Aspartate via RIPK Pathway Modulation and Gut Microbiota Composition in Mice.

The intestine requires a great deal of energy to maintain its health and function; thus, energy deficits in the intestinal mucosa may lead to intestinal damage. Aspartate (Asp) is an essential energy source in the intestinal mucosa and plays a vital part in gut health. In the current study, we hypothesized that dietary supplementation of Asp could alleviate DSS-induced colitis via improvement in the colonic morphology, oxidative stress, cell apoptosis, and microbiota composition in a mouse model of dextran. Asp administration decreased the disease activity index, apoptosis, myeloperoxidase, eosinophil peroxidase, and proinflammatory cytokine (IL-1ß and TNF-α) concentrations in the colonic tissue, but improved the body weight, average daily food intake, colonic morphology, and antioxidant-related gene (GPX1 and GPX4) expression in DSS-treated mice. Expression levels of RIPK1 and RIPK3 were increased in the colon following Asp administration in the DSS-induced mice, whereas the MLKL protein expression was decreased. 16S rRNA sequencing showed that Asp treatment increased the abundance of Lactobacillus and Alistipes at the gene level, and Bacteroidetes at the phylum level, but decreased the abundance of Actinobacteria and Verrucomicrobia at the phylum level. Asp may positively regulate the recovery of DSS-induced damage by improving the immunity and antioxidative capacity, regulating RIPK signaling and modulating the gut microbiota composition.