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Pneumocystis jirovecii, the fungal agent of human Pneumocystis pneumonia, is closely related to macaque Pneumocystis. Little is known about other Pneumocystis species in distantly related mammals, none of which are capable of establishing infection in humans. The molecular basis of host specificity in Pneumocystis remains unknown as experiments are limited due to an inability to culture any species in vitro. To explore Pneumocystis evolutionary adaptations, we have sequenced the genomes of species infecting macaques, rabbits, dogs and rats and compared them to available genomes of species infecting humans, mice and rats. Complete whole genome sequence data enables analysis and robust phylogeny, identification of important genetic features of the host adaptation, and estimation of speciation timing relative to the rise of their mammalian hosts. Our data reveals insights into the evolution of P. jirovecii, the sole member of the genus able to infect humans.

Simple Summary: Changes in physiological and biochemical parameters are crucial for the reproductive performance and health of perinatal ewes. However, dynamic changes in feed utilization, rumen fermentation, and serum biochemical indexes of perinatal ewes are unclear. This study aims to explore dynamic changes in dry matter intake, nutrient digestibility, rumen fermentation, and serum biochemical indexes in perinatal ewes and their relationship with rumen microbiota. We found that the dry matter intake and glucose gradually decreased during prepartum and increased during postpartum. The digestibility of dry matter, crude protein, and acid detergent fiber increased before lambing, and decreased on day 3 after lambing. The concentrations of acetate, propionate, and butyrate gradually decreased before lambing and increased after lambing. The rumen microbiota composition was different in perinatal ewes, and the changes in dry matter intake, serum glucose, acetate, and propionate were related to rumen bacteria (g_Anaerovibrio, g_Lachnobacterium, g_Schwartzia and g_Bacillus). The results provide a basis for the regulation of physiological and biochemical parameters of perinatal ewes by rumen microbiota. Changes in physiological and biochemical parameters are crucial for the reproductive performance and health of perinatal ewes. This study investigated the temporal variations in feed intake, nutrient digestibility, serum parameters, and ruminal fermentation on days 21, 14, and 7 before lambing (Q21, Q14, and Q7) and days 3, 7, and 14 after lambing (H3, H7, and H14). The results showed that dry matter intake (DMI) and glucose (Glu) gradually decreased (p < 0.05) before lambing and increased (p < 0.05) after lambing. The digestibility of dry matter (DMD), crude protein (CPD), and acid detergent fiber (ADFD) increased (p < 0.05) before lambing, then decreased (p < 0.05) on day H3, and then increased (p < 0.05) on day H14. The rumen pH, NH3-N, and triglycerides (TG) gradually increased (p < 0.05) before lambing and were higher (p < 0.05) on day Q7 than after lambing. The concentrations of acetate, butyrate, and total volatile fatty acids (T-VFA) were lower (p < 0.05) on day Q7 than those on days Q21 and Q14, then increased (p < 0.05) after lambing. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) concentrations gradually decreased (p < 0.05) in perinatal ewes. BHBA and NEFA concentrations were lower (p < 0.05) on day Q21 than those from days Q14 to H14. The rumen microbiota compositions were different (p < 0.05) in perinatal ewes, and g_Anaerovibrio, g_Lachnobacterium, and g_Schwartzia were positively correlated (p < 0.05) with DMI, Glu, acetate, propionate, and T-VFA, and negatively correlated (p < 0.05) with LDL-C. g_Bacillus was negatively correlated (p < 0.05) with DMI, Glu, acetate, propionate, butyrate, and T-VFA, but positively correlated (p < 0.05) with rumen pH and LDL-C. In summary, the DMI, nutrient digestibility, rumen fermentation, and serum parameters changed during the perinatal period of ewes, and the changes in DMI, serum glucose, acetate, propionate, and T-VFA were related to the rumen bacteria. [ABSTRACT FROM AUTHOR]

Pneumocystis species are opportunistic mammalian pathogens that cause severe pneumonia in immunocompromised individuals. These fungi are highly host specific and uncultivable in vitro Human Pneumocystis infections present major challenges because of a limited therapeutic arsenal and the rise of drug resistance. To investigate the diversity and demographic history of natural populations of Pneumocystis infecting humans, rats, and mice, we performed whole-genome and large-scale multilocus sequencing of infected tissues collected in various geographic locations. Here, we detected reduced levels of recombination and variations in historical demography, which shape the global population structures. We report estimates of evolutionary rates, levels of genetic diversity, and population sizes. Molecular clock estimates indicate that Pneumocystis species diverged before their hosts, while the asynchronous timing of population declines suggests host shifts. Our results have uncovered complex patterns of genetic variation influenced by multiple factors that shaped the adaptation of Pneumocystis populations during their spread across mammals.IMPORTANCE Understanding how natural pathogen populations evolve and identifying the determinants of genetic variation are central issues in evolutionary biology. Pneumocystis, a fungal pathogen which infects mammals exclusively, provides opportunities to explore these issues. In humans, Pneumocystis can cause a life-threatening pneumonia in immunosuppressed individuals. In analysis of different Pneumocystis species infecting humans, rats, and mice, we found that there are high infection rates and that natural populations maintain a high level of genetic variation despite low levels of recombination. We found no evidence of population structuring by geography. Our comparisons of the times of divergence of these species to their respective hosts suggest that Pneumocystis may have undergone recent host shifts. The results demonstrate that Pneumocystis strains are widely disseminated geographically and provide a new understanding of the evolution of these pathogens.

Simple Summary: Intensively managing the use of concentrate supplementation to complement nutrition can increase production costs and reduce producers' income. Considering the frequently large price fluctuations for soybean meal, an alternative is the replacement of local protein sources in ruminant feeding. In this study, we compared the effects of different sources of protein (soybean meal, cottonseed meal, peanut meal, rapeseed meal, and distillers' dried grains with solubles) on the growth, digestibility, and rumen fermentation of growing lambs. Our results showed that when soybean meal was totally replaced with either cottonseed meal, peanut meal, rapeseed meal, or distillers' dried grains with solubles, there was no impact on the average daily gain of growing lambs, but digestibility was reduced. Our study provides a theoretical basis for the rational selection and utilization of proteins from different sources, which helps us to optimize the feeding management of growing lambs. Considering the frequently large price fluctuations for soybean meal, an alternative is the increased use of locally produced high-protein ingredients. The objective of this study was to evaluate the effects of the total replacement of soybean meal with different sources of protein on the growth performance, nutrient digestibility, serum parameters, rumen fermentation parameters, and bacterial communities in growing lambs. Sixty sheep with similar body weights (38.46 ± 0.71 kg) were distributed to one of five treatments: soybean meal (SBM); cottonseed meal (COM); peanut meal (PEM); rapeseed meal (RAM); and distillers' dried grains with solubles (DDGS). The experiment lasted 62 days with a 10-day adaptation period and a 52-day growing period. The results indicated that the body weight and average daily gain were not affected by different protein sources (p > 0.05), but the dry matter intake of the SBM group was lower than that of the other groups (p < 0.05); otherwise, the feed efficiency was higher (p < 0.05). The digestion of dry matter was higher in the SBM, COM, and RAM groups than in the DDGS and PEM groups (p < 0.05). Meanwhile, compared to the other groups, the SBM group had the highest digestion of gross energy and crude protein (p < 0.05). In addition, the concentration of glutathione peroxidase was highest in the SBM group (p < 0.05). Regarding the rumen fermentation, the SBM group had the highest concentration of NH3-N (p < 0.05). The rumen bacterial community was not affected by treatments (p > 0.05). In conclusion, the total replacement of soybean meal with cottonseed, peanut, rapeseed, or DDGS reduced digestibility but did not impact the body weight or average daily gain of growing lambs and had no effect on the immune function and rumen bacterial community; thus, they can be used to substitute the soybean meal. [ABSTRACT FROM AUTHOR]

Background: Premature ovarian insufficiency (POI) is an important cause of female infertility and seriously impacts the physical and psychological health of patients. Human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exs, H-Exs) have exhibited protective effects on ovarian function with unclear mechanisms. Methods: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify POI-associated circRNAs and miRNAs. The relationship between HucMSC-derived exosomal circBRCA1/miR-642a-5p/FOXO1 axis and POI was examined by RT-qPCR, Western blotting, reactive oxygen species (ROS) staining, senescence-associated β-gal (SA-β-gal) staining, JC-1 staining, TEM, oxygen consumption rate (OCR) measurements and ATP assay in vivo and in vitro. RT-qPCR detected the expression of circBRCA1 in GCs and serum of patients with normal ovarian reserve function (n = 50) and patients with POI (n = 50); then, the correlation of circBRCA1 with ovarian reserve function indexes was analyzed. Results: Herein, we found that circBRCA1 was decreased in the serum and ovarian granulosa cells (GCs) of patients with POI and was associated with decreased ovarian reserve. H-Exs improved the disorder of the estrous cycles and reproductive hormone levels, reduced the number of atretic follicles, and alleviated the apoptosis and senescence of GCs in rats with POI. Moreover, H-Exs mitigated mitochondrial damage and reversed the reduced circBRCA1 expression induced by oxidative stress in GCs. Mechanistically, FTO served as an eraser to increase the stability and expression of circBRCA1 by mediating the m6A demethylation of circBRCA1, and exosomal circBRCA1 sponged miR-642a-5p to block its interaction with FOXO1. CircBRCA1 insufficiency aggravated mitochondrial dysfunction, mimicking FTO or FOXO1 depletion effects, which was counteracted by miR-642a-5p inhibition. Conclusion: H-Exs secreted circBRCA1 regulated by m6A modification, directly sponged miR-642a-5p to upregulate FOXO1, resisted oxidative stress injuries in GCs and protected ovarian function in rats with POI. Exosomal circBRCA1 supplementation may be a general prospect for the prevention and treatment of POI. [ABSTRACT FROM AUTHOR]

Simple Summary: Abnormal prolactin levels can lead to male infertility. However, the regulation mechanism of prolactin in the epididymis is still unclear. We studied the effects of prolactin on the epididymis function of Yanshan Cashmere bucks using the prolactin inhibitor bromocriptine. The results show that the inhibition of prolactin decreased the serum estradiol concentrations and the expression of the prolactin receptor protein in the epididymis (p < 0.05). The inhibition of prolactin also increased the height of the epididymal epithelium in the caput and cauda, as well as the diameter of the epididymal duct in the caput (p < 0.05). Meanwhile, prolactin inhibition decreased the duct diameter in the epididymal cauda (p < 0.05). Then, transcriptome analyses showed that the differentially expressed genes ESR2, MAPK10, JUN, ACTL7A, and CALML4 were enriched in multiple pathways, including the estrogen signaling pathway, the GnRH signaling pathway, the cAMP signaling pathway, the chemical carcinogenesis–reactive oxygen species pathway, steroid binding, and calcium ion binding, which may be the key genes in the prolactin regulation of epididymal function. This study provides new insights into the molecular mechanisms of prolactin regulating epididymis function in bucks. Yanshan Cashmere bucks are seasonal breeding animals and an important national genetic resource. This study aimed to investigate the involvement of prolactin (PRL) in the epididymal function of bucks. Twenty eleven-month-old Cashmere bucks were randomly divided into a control (CON) group and a bromocriptine (BCR, a prolactin inhibitor, 0.06 mg/kg body weight (BW)) treatment group. The experiment was conducted from September to October 2020 in Qinhuangdao City, China, and lasted for 30 days. Blood was collected on the last day before the BCR treatment (day 0) and on the 15th and 30th days after the BCR treatment (days 15 and 30). On the 30th day, all bucks were transported to the local slaughterhouse, where epididymal samples were collected immediately after slaughter. The left epididymis was preserved in 4% paraformaldehyde for histological observation, and the right epididymis was immediately preserved in liquid nitrogen for RNA sequencing (RNA-seq). The results show that the PRL inhibitor reduced the serum PRL and estradiol (E2) concentrations (p < 0.05) and tended to decrease luteinizing hormone (LH) concentrations (p = 0.052) by the 30th day, but no differences (p > 0.05) occurred by either day 0 or 15. There were no differences (p > 0.05) observed in the follicle-stimulating hormone (FSH), testosterone (T), and dihydrotestosterone (DHT) concentrations between the two groups. The PRL receptor (PRLR) protein was mainly located in the cytoplasm and intercellular substance of the epididymal epithelial cells. The PRL inhibitor decreased (p < 0.05) the expression of the PRLR protein in the epididymis. In the BCR group, the height of the epididymal epithelium in the caput and cauda increased, as did the diameter of the epididymal duct in the caput (p < 0.05). However, the diameter of the cauda epididymal duct decreased (p < 0.05). Thereafter, a total of 358 differentially expressed genes (DEGs) were identified in the epididymal tissues, among which 191 were upregulated and 167 were downregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that ESR2, MAPK10, JUN, ACTL7A, and CALML4 were mainly enriched in the estrogen signaling pathway, steroid binding, calcium ion binding, the GnRH signaling pathway, the cAMP signaling pathway, and the chemical carcinogenesis–reactive oxygen species pathway, which are related to epididymal function. In conclusion, the inhibition of PRL may affect the structure of the epididymis by reducing the expression of the PRLR protein and the secretion of E2. ESR2, MAPK10, JUN, ACTL7A, and CALML4 could be the key genes of PRL in its regulation of epididymal reproductive function. [ABSTRACT FROM AUTHOR]

In this work, different proportions of N-doped carbon quantum dots/porous Co3O4 (NCQDs/p-Co3O4) NCQDs/Co3O4 composite photocatalysts were prepared by a simple self-assembly method. It was demonstrated by a series of characterizations that 50% NCQDs/Co3O4 has a good visible light response and low electrochemical impedance. The photocatalytic degradation of TC was investigated by the 50% NCQDs/p-Co3O4 composite photocatalyst, and the results showed that the degradation effect of TC reached 81.2% within 120 min. The higher photocatalytic activity of 50% NCQDs/p-Co3O4 was analyzed probably because NCQDs can improve the separation efficiency of photogenerated electron–hole pairs and p-Co3O4 can provide a larger specific surface area and thus has more active sites. This study provides a new strategy for improving the photodegradation activity of Co3O4 photocatalysts. [ABSTRACT FROM AUTHOR]