Dietary resveratrol improves the flesh quality of Siberian sturgeon (Acipenser baerii) by enhancing myofiber growth, nutrient accumulation and antioxidant capacity.

BACKGROUND: In aquaculture, sturgeons are generally maintained in the confined spaces, which not only hinders sturgeon movement, but also threatens their flesh quality that seriously concerned by aquaculture industry. As a typical antioxidant, resveratrol can improve the flesh quality of livestock and poultry. However, the mechanism of resveratrol's effect on the muscle of Siberian sturgeon is still unclear. RESULTS: In this study, the dietary resveratrol increased the myofiber diameter, the content of the amino acids, antioxidant capacity markers (CAT, LDH and SOD) levels and the expression levels of mTORC1 and MYH9 in muscle of Siberian sturgeon. Further transcriptome analysis displayed that ROS production-related pathways ("Oxidative phosphorylation" and "Chemical carcinogenes-reactive oxygen species") were enriched in KEGG analysis, and the expression levels of genes related to the production of ROS (COX4, COX6A, ATPeF1A, etc.) in mitochondria were significantly down-regulated, while the expression levels of genes related to scavenging ROS (SOD1) were up-regulated. CONCLUSIONS: In summary, this study reveals that resveratrol may promote the flesh quality of Siberian sturgeon probably by enhancing myofiber growth, nutritional value and the antioxidant capacity of muscle, which has certain reference significance for the development of a new type of feed for Siberian sturgeon.

Transcriptome analysis reveals high concentration of resveratrol promotes lipid synthesis and induces apoptosis in Siberian sturgeon (Acipenser baerii).

Resveratrol has been reported to promote immunity and decrease oxidative stress, but which demonstrates biphasic effects relied on the use concentration. In this study, the effects of diet supplement with a relative high concentration of resveratrol (0.32 mg/kg) on metabolism, antioxidation and apoptosis of liver were investigated in Siberian sturgeon. The results showed that resveratrol significantly increased the lipid synthesis and the apoptosis, but did not either activate the antioxidant NRF2/KEAP1 pathway or enhance the antioxidant enzyme activity. Transcriptome analysis revealed significant changes in regulatory pathways related to glycolipid, including PPAR signaling pathway, Insulin signaling pathway, Fatty acid biosynthesis, and Glycolysis/Gluconeogenesis. In addition, resveratrol significantly increased the lipid synthesis genes (accα and fas), fatty acid transport gene (fatp 6) and gluconeogenesis gene (gck), but decreased the survival-promoting genes (gadd45ß and igf 1). These findings highlight a significant effect of resveratrol on glycolipid metabolism in Siberian sturgeon. Moreover, this study also demonstrated that 0.32 mg/kg resveratrol has physiological toxicity to the liver of Siberian sturgeon, indicating that this dose is too high for Siberian sturgeon. Thus, our study provides a valuable insight for future research and application of resveratrol in fish.

Role of TFEB-autophagy lysosomal pathway in palmitic acid induced renal tubular epithelial cell injury.

Lysosomal dysfunction and impaired autophagic flux are involved in the pathogenesis of lipotoxicity in the kidney. Here, we investigated the role of transcription factor EB (TFEB), a master regulator of autophagy-lysosomal pathway, in palmitic acid induced renal tubular epithelial cells injury. We examined lipid accumulation, autophagic flux, expression of Ps211-TFEB, and nuclear translocation of TFEB in HK-2 cells overloaded with palmitic acid (PA). By utilizing immunohistochemistry, we detected TFEB expression in renal biopsy tissues from patients with diabetic nephropathy and normal renal tissue adjacent to surgically removed renal carcinoma (controls), as well as kidney tissues from rat fed with high-fat diet (HFD) and low-fat diet (LFD). We found significant lipid accumulation, increased apoptosis, accompanied with elevated Ps211-TFEB, decreased nuclear TFEB, reduced lysosome biogenesis and insufficient autophagy in HK-2 cells treated with PA. Kidney tissues from patients with diabetic nephropathy had lower nuclear and total levels of TFEB than that in control kidney tissues. Level of renal nuclear TFEB in HFD rats was also lower than that in LFD rats. Exogenous overexpression of TFEB increased the nuclear TFEB level in HK-2 cells treated with PA, promoted lysosomal biogenesis, improved autophagic flux, reduced lipid accumulation and apoptosis. Our results collectively indicate that PA is a strong inducer for TFEB phosphorylation modification at ser211 accompanied with lower nuclear translocation of TFEB. Impairment of TFEB-mediated lysosomal biogenesis and function by palmitic acid may lead to insufficient autophagy and promote HK-2 cells injury.

Transcriptome analysis reveals the high temperature induced damage is a significant factor affecting the osmotic function of gill tissue in Siberian sturgeon (Acipenser baerii).

BACKGROUND: Maintaining osmotic equilibrium plays an important role in the survival of cold-water fishes. Heat stress has been proven to reduce the activity of Na+/K+-ATPase in the gill tissue, leading to destruction of the osmotic equilibrium. However, the mechanism of megatemperature affecting gill osmoregulation has not been fully elucidated. RESULTS: In this study, Siberian sturgeon (Acipenser baerii) was used to analyze histopathological change, plasma ion level, and transcriptome of gill tissue subjected to 20℃, 24℃and 28℃. The results showed that ROS level and damage were increased in gill tissue with the increasing of heat stress temperature. Plasma Cl- level at 28℃ was distinctly lower than that at 20℃ and 24℃, while no significant difference was found in Na+ and K+ ion levels among different groups. Transcriptome analysis displayed that osmoregulation-, DNA-repair- and apoptosis-related terms or pathways were enriched in GO and KEGG analysis. Moreover, 194 osmoregulation-related genes were identified. Amongst, the expression of genes limiting ion outflow, occluding (OCLN), and ion absorption, solute carrier family 4, member 2 (AE2) solute carrier family 9, member 3 (NHE3) chloride channel 2 (CLC-2) were increased, while Na+/K+-ATPase alpha (NKA-a) expression was decreased after heat stress. CONCLUSIONS: This study reveals for the first time that the effect of heat stress on damage and osmotic regulation in gill tissue of cold-water fishes. Heat stress increases the permeability of fish's gill tissue, and induces the gill tissue to keep ion balance through active ion absorption and passive ion outflow. Our study will contribute to research of global-warming-caused effects on cold-water fishes.

UNC93B1 facilitates TLR18-mediated NF-κB signal activation in Schizothorax prenanti.

Toll-like receptor 18 (TLR18), a non-mammalian TLR, has been believed to play an important role in anti-bacterial immunity of teleost fishes. UNC93B1 is a classical molecular chaperone that mediates TLRs transport from endoplasmic reticulum to the located membrane. However, TLR18-mediated signal transduction mechanism and the regulatory effect of UNC93B1 to TLR18 are still unclear in teleost fishes. In this study, the coding sequences of TLR18 and UNC93B1 were cloned from Schizothorax prenanti, named spTLR18 and spUNC93B1, respectively. The spTLR18 and spUNC93B1 are 2583 bp and 1878 bp in length, encode 860 and 625 amino acids, respectively. The spTLR18 widely expressed in various tissues with the highest expression level in liver. After stimulation of Aeromonas hydrophila, lipopolysaccharide (LPS) and Poly(I:C), the expression levels of spTLR18 were significantly increased in spleen and head kidney. The spTLR18 located in the cell membrane, while spUNC93B1 located in the cytoplasm. Luciferase and overexpression analysis showed that spTLR18 activated NF-κB and type I IFN signal pathways, and spTLR18-mediated NF-κB activation might depend on the adaptor molecule MyD88. Besides, spUNC93B1 positively regulates spTLR18-mediated NF-κB signal. Our study first uncovers TLR18-UNC93B1-mediated signal transduction mechanism, which contributes to the understanding of TLR signaling pathway in teleost fishes.

PNX14 but not PNX20 as a novel regulator of preadipocyte differentiation via activating Epac-ERK signaling pathway in Gallus gallus.

Small integral membrane protein 20 (SMIM20) could generate two main peptides, PNX14 and PNX20, which participate in multiple biological roles such as reproduction, inflammation and energy metabolism in mammals. However, little is known about their physiological functions in non-mammalian vertebrates. Using chicken (c-) as an animal model, we found cSMIM20 was moderately expressed in adipose tissues, and its expression was gradually increased during the differentiation of chicken preadipocytes, suggesting that it may play an important role in chicken adipogenesis. Further research showed cPNX14 could facilitate the differentiation of chicken preadipocytes into mature adipocytes by enhancing expression of adipogenic genes including PPARγ, CEBPα and FABP4, and promoting the formation of lipid droplets. This pro-adipogenic effect of cPNX14 was completely attenuated by Epac-specific and ERK inhibitor. Interestingly, cPNX20 failed to regulate the adipogenic genes and lipid droplet content. Collectively, our findings reveal that cPNX14 but not cPNX20 can serve as a novel adipogenesis mediator by activating the Epac-ERK signaling pathway in chickens.

Mechanic Insight into the Distinct and Common Roles of Ovariectomy Versus Adrenalectomy on Adipose Tissue Remodeling in Female Mice.

Dysfunctions of the ovaries and adrenal glands are both evidenced to cause aberrant adipose tissue (AT) remodeling and resultant metabolic disorders, but their distinct and common roles are poorly understood. In this study, through biochemical, histological and RNA-seq analyses, we comprehensively explored the mechanisms underpinning subcutaneous (SAT) and visceral adipose tissue (VAT) remodeling, in response to ovariectomy (OVX) versus adrenalectomy (ADX) in female mice. OVX promoted adipocyte differentiation and fat accumulation in both SAT and VAT, by potentiating the Pparg signaling, while ADX universally prevented the cell proliferation and extracellular matrix organization in both SAT and VAT, likely by inactivating the Nr3c1 signaling, thus causing lipoatrophy in females. ADX, but not OVX, exerted great effects on the intrinsic difference between SAT and VAT. Specifically, ADX reversed a large cluster of genes differentially expressed between SAT and VAT, by activating 12 key transcription factors, and thereby caused senescent cell accumulation, massive B cell infiltration and the development of selective inflammatory response in SAT. Commonly, both OVX and ADX enhance circadian rhythmicity in VAT, and impair cell proliferation, neurogenesis, tissue morphogenesis, as well as extracellular matrix organization in SAT, thus causing dysfunction of adipose tissues and concomitant metabolic disorders.

Efficacy of Immunization against a Novel Synthetic 13-Amino Acid Betaglycan-Binding Peptide Sequence of Inhibin α Subunit on Promoting Fertility in Female Rats.

Inhibins suppress the FSH production in pituitary gonadotrope cells by robustly antagonizing activin signaling by competitively binding to activin type II receptors (ACTR II). The binding of inhibin A to ACTR II requires the presence of its co-receptor, namely, betaglycan. In humans, the critical binding site for betaglycan to inhibin A was identified on the inhibin α subunit. Through conservation analysis, we found that a core 13-amino-acid peptide sequence within the betaglycan-binding epitope on human inhibin α subunit is highly conserved across species. Based on the tandem sequence of such a conserved 13-amino-acid betaglycan-binding epitope (INHα13AA-T), we developed a novel inhibin vaccine and tested its efficacy in promoting female fertility using the female rat as a model. Compared with placebo-immunized controls, INHα13AA-T immunization induced a marked (p < 0.05) antibody generation, enhanced (p < 0.05) ovarian follicle development, and increased ovulation rate and litter sizes. Mechanistically, INHα13AA-T immunization promoted (p < 0.05) pituitary Fshb transcription and increased (p < 0.05) serum FSH and 17ß-estradiol concentrations. In summary, active immunization against INHα13AA-T potently increased FSH levels, ovarian follicle development, ovulation rate and litter sizes, thus causing super-fertility in females. Therefore, immunization against INHα13AA is a promising alternative to the conventional approach of multiple ovulation and super-fertility in mammals.

Effect of Purslane (Portulaca oleracea L.) on Intestinal Morphology, Digestion Activity and Microbiome of Chinese Pond Turtle (Mauremys reevesii) during Aeromonas hydrophila Infection.

Large-scale mortality due to Aeromonas hydrophila (A. hydrophila) infection has considerably decreased the yield of the Chinese pond turtle (Mauremys reevesii). Purslane is a naturally active substance with a wide range of pharmacological functions, but its antibacterial effect on Chinese pond turtles infected by A. hydrophila infection is still unknown. In this study, we investigated the effect of purslane on intestinal morphology, digestion activity, and microbiome of Chinese pond turtles during A. hydrophila infection. The results showed that purslane promoted epidermal neogenesis of the limbs and increased the survival and feeding rates of Chinese pond turtles during A. hydrophila infection. Histopathological observation and enzyme activity assay indicated that purslane improved the intestinal morphology and digestive enzyme (α-amylase, lipase and pepsin) activities of Chinese pond turtle during A. hydrophila infection. Microbiome analysis revealed that purslane increased the diversity of intestinal microbiota with a significant decrease in the proportion of potentially pathogenic bacteria (such as Citrobacter freundii, Eimeria praecox, and Salmonella enterica) and an increase in the abundance of probiotics (such as uncultured Lactobacillus). In conclusion, our study uncovers that purslane improves intestinal health to protect Chinese pond turtles against A. hydrophila infection.

Spexin2 Is a Novel Food Regulator in Gallus gallus.

Spexin2 (SPX2), a paralog of SPX1, is a newly identified gene in non-mammalian vertebrates. Limited studies in fish have evidenced its important role in food intake and energy balance modulation. However, little is known about its biological functions in birds. Using the chicken (c-) as a model, we cloned the full-length cDNA of SPX2 by using RACE-PCR. It is 1189 base pair (bp) in length and predicted to generate a protein of 75 amino acids that contains a 14 amino acids mature peptide. Tissue distribution analysis showed that cSPX2 transcripts were detected in a wide array of tissues, with abundant expression in the pituitary, testis, and adrenal gland. cSPX2 was also observed to be ubiquitously expressed in chicken brain regions, with the highest expression in the hypothalamus. Its expression was significantly upregulated in the hypothalamus after 24 or 36 h of food deprivation, and the feeding behavior of chicks was obviously suppressed after peripheral injection with cSPX2. Mechanistically, further studies evidenced that cSPX2 acts as a satiety factor via upregulating cocaine and amphetamine regulated transcript (CART) and downregulating agouti-related neuropeptide (AGRP) in hypothalamus. Using a pGL4-SRE-luciferase reporter system, cSPX2 was demonstrated to effectively activate a chicken galanin II type receptor (cGALR2), a cGALR2-like receptor (cGALR2L), and a galanin III type receptor (cGALR3), with the highest binding affinity for cGALR2L. Collectively, we firstly identified that cSPX2 serves as a novel appetite monitor in chicken. Our findings will help clarify the physiological functions of SPX2 in birds as well as its functional evolution in vertebrates.

[Blood Lipid Indicators and Different Clinical Classifications of Dyslipidemia and Diabetic Kidney Disease: Correlation and Predictive Value].

Objective: To explore the relationship between blood lipid indicators and different clinical classifications of dyslipidemia and diabetic kidney disease (DKD) and to compare the value of different clinical classifications of dyslipidemia for predicting DKD. Methods: Continuously enrollment of subjects was conducted at the First Affiliated Hospital of Chongqing Medical University and the Yongchuan Hospital of Chongqing Medical University between October 2020 and October 2021. A total of 356 type 2 diabetes mellitus (T2DM) patients admitted to the two hospitals were enrolled. They were divided into DKD group ( n=126) and simple T2DM group ( n=230) according to whether their T2DM was combined with DKD. In addition, 250 healthy individuals undergoing physical examination during the same period were enrolled for the control group. The blood pressure, blood lipid, blood glucose, and the kidney function indicators of the three groups were measured. The effects of different classifications of dyslipidemia on DKD were analyzed with unconditional logistic regression models, the receiver operating characteristic (ROC) curve was constructed, the area under the curve ( AUC) of ROC was calculated, and the value of different classifications of dyslipidemia for predicting DKD was analyzed. Results: The diastolic blood pressure (DBP), systolic blood pressure (SBP), total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C), serum creatinine (Scr), uric acid (UA), and glycosylated hemoglobin A1c (HbA1c) of the DKD group and the simple T2DM group were significantly higher than those of the control group, while the high-density lipoprotein cholesterol (HDL-C) levels of the DKD group and the simple T2DM group were lower than that of the control group (all P<0.05). The disease course of T2DM, DBP, SBP, TC, TG, Scr, UA and HbA1c of the DKD group were significantly higher than those of the T2DM group (all P<0.05). After adjusting for the effects of T2DM disease course, DBP, SBP, Scr, UA and HbA1c, the results showed that TC ( OR=1.426, 95% CI: 1.088-1.868) and TG ( OR=1.404, 95% CI: 1.075-1.833) were independent risk factors for DKD, and that hypercholesterolemia ( OR=1.817, 95% CI: 1.040-3.177) and mixed hyperlipidemia ( OR=2.148, 95% CI: 1.110-4.159) were independent risk factors for DKD (all P<0.05). The AUC (95% CI) of hypercholesterolemia was 0.789 (0.729-0.871). The AUC (95% CI) of mixed hyperlipidemia was 0.671 (0.579-0.760). Hypercholesterolemia showed better predictive value for the diagnosis and prediction of DKD. Conclusion: Among the blood lipid indicators, TC and TG are independent risk factors of DKD. In the clinical classifications of dyslipidemia, hypercholesterolemia and mixed hyperlipidemia are independent risk factors of DKD. Hypercholesterolemia can be used as a predictor to screen for DKD among T2DM patients and is well suited for extensive application in outpatient screening.

RNA-seq coupling two different methods of castration reveals new insights into androgen deficiency-caused degeneration of submaxillary gland in male Sprague Dawley rats.

BACKGROUND: Salivary gland (SMG) degeneration and dysfunction are common symptoms that occur after sex hormone deprivation, but the underlying mechanisms remain largely unknown. Additionally, immunocastration, which causes drop of sex hormones, has been developed as an alternative to surgical castration, however whether it exerts similar effects as surgical castration on the salivary glands is unknown. Through histological and RNA-seq analysis, we assessed changes in morphology and transcriptome of SMG in response to immunocastration (IM) versus surgical castration (bilateral orchiectomy, ORC). RESULTS: Compared to entire males (EM), ORC caused severe degeneration of SMG in rats, as evidenced by both decreased (P < 0.01) SMG weight and organ index, and by decreased (P < 0.01) quantity of SMG acini and ducts. IM had minimal effects (P > 0.05) on SMG weight and organ index, but it still caused degeneration (P < 0.05) of the acini and ducts. Even though, the quantity of both SMG acini and ducts was much higher (P < 0.001) in IM than in ORC. Functional enrichment analysis of the common regulated genes by ORC/IM revealed disrupted epithelial cell development, angiogenesis, anatomical structure morphogenesis and enhanced cell death are associated with SMG degeneration in deprivation of androgens. Integrated data analysis shown that there existed a selective hyperfunction of SMG ribosome and mitochondrion in ORC but not in IM, which might be associated with more severe degeneration of SMG in ORC than in IM. CONCLUSIONS: Our findings suggested that both surgical castration and immunocastration caused SMG degeneration by disrupting epithelial cell development, angiogenesis, anatomical structure morphogenesis and enhancing cell death. But, surgical castration selectively induced hyperfunction of SMG ribosome and mitochondrion, thus causing more severe degeneration of SMG than immunocastration.

Identification and functional characteristics of two TLR5 subtypes in S. grahami.

TLR5, as a member of Toll-like receptors (TLRs) family in mammals, is responsible for recognizing bacterial flagellin and initiating innate immunity, but its function is still unclear in fish species. In this study, two family members of TLR5 were cloned and identified from Sinocyclocheilus grahami (S. grahami), named sgTLR5a and sgTLR5b. The length of coding sequence of sgTLR5a and sgTLR5b is 2,622 bp and 2,658 bp, encoding 873 and 885 amino acids, respectively. Molecular phylogenetic analysis indicates that sgTLR5a and sgTLR5b have the closest genetic relationship with TLR5M (membrane-type) of Cyprinus carpio and Schizothorax prenanti, respectively. sgTLR5a and sgTLR5b were widely expressed in various tested tissues, of which the expression levels were the highest in skin tissue. After stimulations of Aeromonas hydrophila (A. hydrophila) and flagellin, the expression levels of sgTLR5a and sgTLR5b in liver, spleen and head kidney tissues were strongly up-regulated, but LPS stimulation only increased the expression of sgTLR5b in these tissues. The luciferase reporter assay displayed that sgTLR5a and sgTLR5b could specifically recognize bacterial flagellin and A. hydrophila and activate the downstream NF-κB signaling pathway in HEK293T cells. Moreover, the overexpression of sgTLR5a and sgTLR5b in EPC cells up-regulated the expression levels of IL-8 and TNF. sgTLR5a and sgTLR5b were observed to locate in the intracellular region by confocal microscope. Interestingly, we found that the NF-κB signaling pathway was positively regulated by co-transfecting sgTLR5a or sgTLR5b with TLR trafficking chaperone sgUNC93B1. In conclusion, our results reveal sgTLR5a and sgTLR5b may play an important role in antibacterial response by activating the NF-κB signaling pathway.

Characterization of prolactin (PRL) and PRL receptor (PRLR) in Chinese soft-shelled turtle: Molecular identification, ligand-receptor interaction and tissue distribution.

Prolactin (PRL) plays crucial roles in many physiological and pathological processes through activating its specific membrane-anchored receptor (PRLR). Although this ligand-receptor pair has been extensively studied in mammals, birds and fishes, researches examining their significance is rather scarce in reptiles. Additionally, the interaction mechanism of PRL-PRLR has abortively understood across vertebrates, since two tandem repeated ligand-binding domains of PRLR have been identified in birds and few reptiles. To lay the foundation to clarify their roles and ligand-receptor interaction in reptiles, using Chinese soft-shelled turtle as model, the cDNAs containing open reading frame of PRL and PRLR were cloned. The cloned PRL consisted of 710 bp and encoded a precursor of 228 amino acid (-aa), while PRLR was 2658 bp in length and predicted to generate a 828-aa precursor. Furthermore, the recombinant PRL protein with high-purity was prepared from Escherichia coli (E. coli) strain Rosetta gamiB (DE3) by using cobalt resin. Using the 5 × STAT5-Luciferase reporter system, we found PRLR and PRLR-M2 (the PRLR-mutant lacking membrane-distal ligand-binding domain) could be dose-dependently activated by recombinant PRL, thereby triggering the intracellular JAK2-STAT5 signaling cascade, suggesting PRL-PRLR is functional in Chinese soft-shelled turtle, and the membrane-proximal ligand-binding domain of PRLR is the critical domain involving in PRL-binding. Quantitative real-time PCR revealed that PRL was predominantly and abundantly expressed in pituitary, while PRLR exhibited ubiquitous expression in all of the tissues examined. Collectively, our data indicate the PRL-PRLR pair may function in reptiles including Chinese soft-shelled turtle, in a way similar to that in birds.

Prognosis and risk factors for cardiac valve calcification in Chinese end-stage kidney disease patients on combination therapy with hemodialysis and hemodiafiltration.

BACKGROUND: Cardiac valve calcification (CVC) is an important risk factor for cardiovascular complications. However, limited data are available concerning the prevalence, clinical features and risk factors for CVC in end-stage kidney disease (ESKD) patients. In this study, we aimed to assess these parameters in Chinese ESKD patients receiving combination therapy with hemodialysis and hemodiafiltration. METHODS: We conducted a cross-sectional study on 293 ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration at the First Affiliated Hospital of Chongqing Medical University from October 2014 to December 2015. CVC was evaluated via echocardiography. RESULTS: ESKD patients with CVC had a higher prevalence of diabetes mellitus, aortic and/or coronary artery calcification, arrhythmia, heart failure and coronary heart disease; increased systolic, diastolic and pulse pressure; longer duration of hemodialysis and hypertension; reduced hemoglobin, albumin and high-density lipoprotein cholesterol levels; and increased serum calcium and calcium-phosphorus product levels compared with those without CVC. Logistic regression analysis showed that increased dialysis duration (p = 0.006, OR = 2.25), serum calcium levels (p = 0.046, OR = 2.04) and pulse pressure (p < 0.001, OR = 3.22), the presence of diabetes (p = 0.037, OR = 1.81) and decreased serum albumin levels (p = 0.047, OR = 0.54) were risk factors for CVC. The correlation analysis indicated a significantly increased CVCs prevalence with an increase prevalence of heart failure, aortic and coronary artery calcification. CONCLUSIONS: CVC represents a common complication and a danger signal for cardiovascular events in ESKD patients undergoing combination therapy of hemodialysis and hemodiafiltration. The presence of diabetes, increased pulse pressure, long dialysis duration, hypoalbuminemia and high serum calcium levels were independent risk factors for CVC.

Two Synthetic Peptides Corresponding to the Human Follicle-Stimulating Hormone ß-Subunit Promoted Reproductive Functions in Mice.

A follicle stimulating hormone (FSH) is widely used in the assisted reproduction and a synthetic peptide corresponding to a receptor binding region of the human (h) FSH-ß-(34−37) (TRDL) modulated reproduction. Furthermore, a 13-amino acid sequence corresponding to hFSH-ß-(37−49) (LVYKDPARPKIQK) was recently identified as the receptor binding site. We hypothesized that the synthetic peptides corresponding to hFSH-ß-(37−49) and hFSH-ß-(34−49), created by merging hFSH-ß-(34−37) and hFSH-ß-(37−49), modulate the reproductive functions, with the longer peptide being more biologically active. In male or female prepubertal mice, a single injection of 200 µg/g BW ip of hFSH-ß-(37−49) or hFSH-ß-(34−49) hastened (p < 0.05) puberty, whereas the same treatments given daily for 4 d promoted (p < 0.05) the gonadal steroidogenesis and gamete formation. In addition of either peptide to the in vitro cell cultures, promoted (p < 0.05) the proliferation of primary murine granulosa cells and the estradiol production by upregulating the expression of Ccnd2 and Cyp19a1, respectively. In adult female mice, 200 µg/g BW ip of either peptide during diestrus antagonized the FSH-stimulated estradiol increase and uterine weight gain during proestrus. Furthermore, hFSH-ß-(34−49) was a more potent (p < 0.05) reproductive modulator than hFSH-ß-(37−49), both in vivo and in vitro. We concluded that hFSH-ß-(37−49) and especially hFSH-ß-(34−49), have the potential for reproductive modulation.

Resveratrol Improves the Digestive Ability and the Intestinal Health of Siberian Sturgeon.

The lack of detailed information on nutritional requirement results in limited feeding in Siberian sturgeon. In this study, resveratrol, a versatile natural extract, was supplemented in the daily diet, and the digestive ability and microbiome were evaluated in the duodena and valvular intestines of Siberian sturgeon. The results showed that resveratrol increased the activity of pepsin, α-amylase, and lipase, which was positively associated with an increase in the digestive ability, but it did not influence the final body weight. Resveratrol improved the digestive ability probably by distinctly enhancing intestinal villus height. Microbiome analysis revealed that resveratrol changed the abundance and composition of the microbial community in the intestine, principally in the duodenum. Random forests analysis found that resveratrol significantly downregulated the abundance of potential pathogens (Citrobacter freundii, Vibrio rumoiensis, and Brucella melitensis), suggesting that resveratrol may also improve intestinal health. In summary, our study revealed that resveratrol improved digestive ability and intestinal health, which can contribute to the development of functional feed in Siberian sturgeon.

[A Cross-sectional Study of Osteoporosis and Cardiovascular Calcification in Patients with Chronic Kidney Disease at Different CKD Stages].

OBJECTIVE: To investigate the status of osteoporosis and cardiovascular calcification in patients with chronic kidney disease (CKD) with different stages, and analyze the correlation between the stages and markers of bone metabolism To correlation. METHODS: A total of 368 CKD patients at stage 3-5 who were treated in First Affiliated Hospital Affiliate to Chongqing Medical University and Chongqing Fuling Central Hospital from July 2017 to January 2018 were enrolled. A total of 60 healthy people who underwent physical examination in the hospital during the same period were enrolled as control group. Age, gender and body mass index (BMI) of all study objects at enrollment time were collected. The levels of estimate glomerular filtration rate (eGFR), serum calcium (Ca), phosphorus (P), albumin (ALB), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BALP), procollagen Ⅰ N-terminal peptide (PINP) and ß-crosslaps (ß-CTX) were detected. The occurrence of osteoporosis, vascular calcification and heart valve calcification was detected. Pearson correlation analysis was applied to analyze correlation between eGFR, serum bone metabolism markers and osteoporosis, cardiovascular calcification. RESULTS: Compared with control group, levels of serum P, iPTH, BALP, PINP and ß-CTX were significantly increased in CKD stage 3-5 group ( P<0.05), while levels of eGFR and serum Ca were decreased ( P<0.05). With the increase of CKD staging, changes of their levels were more significant ( P<0.05). The incidence of vascular calcification and heart valve calcification in CKD stage 5 hemodialysis group was higher than that in CKD stage 3-4 group and CKD stage 5 without dialysis group ( P<0.05). eGFR was positively correlated with serum Ca in CKD patients at stage 3-5 ( P<0.05), while negatively correlated with serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). The occurrence of osteoporosis, vascular calcification and heart valve calcification was negatively correlated with increase of eGFR and serum Ca levels in CKD patients at stage 3-5 ( P<0.05), while positively correlated with increase of levels of serum P, iPTH, BALP, PINP and ß-CTX ( P<0.05). CONCLUSION: The levels of serum bone metabolism markers and eGFR are closely related to occurrence of osteoporosis and cardiovascular calcification in CKD patients at stage 3-5.

PINK1/Parkin mediated mitophagy ameliorates palmitic acid-induced apoptosis through reducing mitochondrial ROS production in podocytes.

Diabetic nephropathy (DN), the primary cause of end-stage renal disease (ESRD), is often accompanied by dyslipidemia, which is closely related to the occurrence and development of DN and even the progression to ESRD. Mitophagy, the selective degradation of damaged and dysfunctional mitochondria by autophagy, is a crucial mitochondrial quality control mechanism, and largely regulated by PINK1 (PTEN-induced putative kinase 1)/Parkin signaling pathway. In the present study, we demonstrated that PA induced mitochondrial damage and excessive mitoROS generation in podocytes. We also found PA treatment resulted in the activation of mitophagy by increasing co-localization of GFP-LC3 with mitochondria and enhancing the formation of mitophagosome, stabilization of PINK1 and mitochondrial translocation of Parkin, which indicated that PINK1/Parkin pathway was involved in PA-induced mitophagy in podocytes. Furthermore, inhibition of mitophagy by silencing Parkin dramatically aggravated PA-induced mitochondrial dysfunction, mitoROS production, and further enhanced PA-induced apoptosis of podocytes. Finally, we showed that PINK1/Parkin pathway were up-regulated in kidney of high fat diet (HFD)-induced obese rats. Taken together, our results suggest that PINK1/Parkin mediated mitophagy plays a protective role in PA-induced podocytes apoptosis through reducing mitochondrial ROS production and that enhancing mitophagy provides a potential therapeutic strategy for kidney diseases with hyperlipidemia, such as DN.

Phenotype-to-genotype approach reveals head-circumference-associated genes in an autism spectrum disorder cohort.

The genotype-first approach has been successfully applied and has elucidated several subtypes of autism spectrum disorder (ASD). However, it requires very large cohorts because of the extensive genetic heterogeneity. We investigate the alternate possibility of whether phenotype-specific genes can be identified from a small group of patients with specific phenotype(s). To identify novel genes associated with ASD and abnormal head circumference using a phenotype-to-genotype approach, we performed whole-exome sequencing on 67 families with ASD and abnormal head circumference. Clinically relevant pathogenic or likely pathogenic variants account for 23.9% of patients with microcephaly or macrocephaly, and 81.25% of those variants or genes are head-size associated. Significantly, recurrent pathogenic mutations were identified in two macrocephaly genes (PTEN, CHD8) in this small cohort. De novo mutations in several candidate genes (UBN2, BIRC6, SYNE1, and KCNMA1) were detected, as well as one new candidate gene (TNPO3) implicated in ASD and related neurodevelopmental disorders. We identify genotype-phenotype correlations for head-size-associated ASD genes and novel candidate genes for further investigation. Our results also suggest a phenotype-to-genotype strategy would accelerate the elucidation of genotype-phenotype relationships for ASD by using phenotype-restricted cohorts.