Chromophore supply modulates cone function and survival in retinitis pigmentosa mouse models.

Retinitis pigmentosa (RP) is an ocular disease characterized by the loss of night vision, followed by the loss of daylight vision. Daylight vision is initiated in the retina by cone photoreceptors, which are gradually lost in RP, often as bystanders in a disease process that initiates in their neighboring rod photoreceptors. Using physiological assays, we investigated the timing of cone electroretinogram (ERG) decline in RP mouse models. A correlation between the time of loss of the cone ERG and the loss of rods was found. To investigate a potential role of the visual chromophore supply in this loss, mouse mutants with alterations in the regeneration of the retinal chromophore, 11-cis retinal, were examined. Reducing chromophore supply via mutations in Rlbp1 or Rpe65 resulted in greater cone function and survival in a RP mouse model. Conversely, overexpression of Rpe65 and Lrat, genes that can drive the regeneration of the chromophore, led to greater cone degeneration. These data suggest that abnormally high chromophore supply to cones upon the loss of rods is toxic to cones, and that a potential therapy in at least some forms of RP is to slow the turnover and/or reduce the level of visual chromophore in the retina.

Genomic dissection of additive and non-additive genetic effects and genomic prediction in an open-pollinated family test of Japanese larch.

Genomic dissection of genetic effects on desirable traits and the subsequent use of genomic selection hold great promise for accelerating the rate of genetic improvement of forest tree species. In this study, a total of 661 offspring trees from 66 open-pollinated families of Japanese larch (Larix kaempferi (Lam.) Carrière) were sampled at a test site. The contributions of additive and non-additive effects (dominance, imprinting and epistasis) were evaluated for nine valuable traits related to growth, wood physical and chemical properties, and competitive ability using three pedigree-based and four Genomics-based Best Linear Unbiased Predictions (GBLUP) models and used to determine the genetic model. The predictive ability (PA) of two genomic prediction methods, GBLUP and Reproducing Kernel Hilbert Spaces (RKHS), was compared. The traits could be classified into two types based on different quantitative genetic architectures: for type I, including wood chemical properties and Pilodyn penetration, additive effect is the main source of variation (38.20-67.46%); for type II, including growth, competitive ability and acoustic velocity, epistasis plays a significant role (50.76-91.26%). Dominance and imprinting showed low to moderate contributions (< 36.26%). GBLUP was more suitable for traits of type I (PAs = 0.37-0.39 vs. 0.14-0.25), and RKHS was more suitable for traits of type II (PAs = 0.23-0.37 vs. 0.07-0.23). Non-additive effects make no meaningful contribution to the enhancement of PA of GBLUP method for all traits. These findings enhance our current understanding of the architecture of quantitative traits and lay the foundation for the development of genomic selection strategies in Japanese larch.

Unraveling the role of PlARF2 in regulating deed formancy in Paeonia lactiflora.

MAIN CONCLUSION: PlARF2 can positively regulate the seed dormancy in Paeonia lactiflora Pall. and bind the RY cis-element. Auxin, a significant phytohormone influencing seed dormancy, has been demonstrated to be regulated by auxin response factors (ARFs), key transcriptional modulators in the auxin signaling pathway. However, the role of this class of transcription factors (TFs) in perennials with complex seed dormancy mechanisms remains largely unexplored. Here, we cloned and characterized an ARF gene from Paeonia lactiflora, named PlARF2, which exhibited differential expression levels in the seeds during the process of seed dormancy release. The deduced amino acid sequence of PlARF2 had high homology with those of other plants and contained typical conserved Auxin_resp domain of the ARF family. Phylogenetic analysis revealed that PlARF2 was closely related to VvARF3 in Vitis vinifera. The subcellular localization and transcriptional activation assay showed that PlARF2 is a nuclear protein possessing transcriptional activation activity. The expression levels of dormancy-related genes in transgenic callus indicated that PlARF2 was positively correlated with the contents of PlABI3 and PlDOG1. The germination assay showed that PlARF2 promoted seed dormancy. Moreover, TF Centered Yeast one-hybrid assay (TF-Centered Y1H), electrophoretic mobility shift assay (EMSA) and dual-luciferase reporter assay analysis (Dual-Luciferase) provided evidence that PlARF2 can bind to the 'CATGCATG' motif. Collectively, our findings suggest that PlARF2, as TF, could be involved in the regulation of seed dormancy and may act as a repressor of germination.

Bacillus subtilis partially inhibits African swine fever virus infection in vivo and in vitro based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II.

IMPORTANCE: African swine fever virus (ASFV) is a highly fatal swine disease that severely affects the pig industry. Although ASFV has been prevalent for more than 100 years, effective vaccines or antiviral strategies are still lacking. In this study, we identified four Bacillus subtilis strains that inhibited ASFV proliferation in vitro. Pigs fed with liquid biologics or powders derived from four B. subtilis strains mixed with pellet feed showed reduced morbidity and mortality when challenged with ASFV. Further analysis showed that the antiviral activity of B. subtilis was based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II. Our findings offer a promising new strategy for the prevention and control of ASFV that may significantly alleviate the economic losses in the pig industry.

Different bone health progression patterns and early-stage risk marker in glucocorticoid-treated ambulatory Duchenne muscular dystrophy.

Fractures often cause irreversible harm in Duchenne muscular dystrophy (DMD). This study investigated the trajectory of bone mineral density (BMD) using group-based trajectory modeling and identified that BMD acts as an early-stage indicator of clinically significant bone fragility. The greater the early-stage BMD, the better the 4-year bone health outcome. PURPOSE: Most Duchenne muscular dystrophy (DMD) children suffer bone loss after long-term glucocorticoid (GC) exposure, which induces scoliosis and fragility fractures. To assess the BMD progression pattern and individual medical risk markers for these phenotypes in young ambulatory boys with DMD, and provide evidence-based suggestions for clinical management of bone health. METHODS: A retrospective longitudinal cohort study of 153 boys with DMD in West China Second University Hospital (2016-2023) was performed. Group-based trajectory modeling was used to study the BMD progression pattern, and potential predictors were further analyzed by logistic regression and survival analysis. RESULTS: One hundred and fifty-three participants were included, 71 of which had more than 3 BMD records. Three BMD trajectories were identified. Baseline BMD and age-started GC and were independent predictors of trajectory attribution. The median survival time of the first observation of low BMD in GC-treated DMD boys was 5.32 (95% CI 4.05-6.59) years, and a significant difference was tested (P < 0.001) among the three trajectory groups. CONCLUSION: BMD may serve as a novel early indicating marker for monitoring bone fragility for DMD. We proposed a bone health risk stratification through BMD progression trajectory that allows us to adapt the osteoporosis warning sign in DMD from a fixed threshold approach to a more individualized strategy, where baseline BMD and age of glucocorticoid initiation can provide an earlier prediction of bone loss. Better management of primary BMD may be able to delay or avoid the onset of adverse bone health outcomes in the fifth year in children with DMD.

IL-1ß induced down-regulation of miR-146a-5p promoted pyroptosis and apoptosis of corneal epithelial cell in dry eye disease through targeting STAT3.

AIM: To elaborate the underlying mechanisms by which IL-1ß promote progression of Dry eye disease(DED) through effect on pyroptosis and apoptosis of corneal epithelial cells(CECs). METHODS: 400 mOsM solutions were used to establish the DED model (hCECs- DED). RT-qPCR was performed to measure IL-1ß mRNA and miR-146a-5p in CECs. Western blotting was performed to measure STAT3, GSDMD, NLRP3, and Caspase-1 levels. Cell counting kit-8 assay was adopted to check cell viability. Apoptosis was detected by flow cytometry. ELISAs were performed to determine IL-18, IL-33 and LDH. The luciferase test detects targeting relationships. RESULTS: After treatment with 400 mOsM solution, cell viability decreased and apoptosis increased. Compared with hCECs, IL-1ß was increased and miR-146a-5p was decreased in hCECs-DED. At the same time, GSDMD, NLRP3, Caspase-1, IL-18, IL-33 and LDH were significantly higher in hCECs-DED than in hCECs, while IL-1ß silencing reversed this effect. In addition, IL-1ß negatively regulated miR-146a-5p. MiR-146a-5p mimics eliminated the inhibition of hCECs-DED pyroptosis and apoptosis caused by IL-1ß silencing. At the same time, miR-146a-5p reduced STAT3 levels in hCECs. CONCLUSION: Highly expressed IL-1ß promoted pyroptosis and apoptosis of hCECs- DED through downregulated miR-146a-5p and inhibited STAT3.

An electrochemical immunosensor based on hybrid self-assembled monolayers for rapid detection of Bombyx mori nucleopolyhedrovirus.

Bombyx mori nucleopolyhedrovirus (BmNPV) is highly contagious and poses a serious threat to sericulture production. Because there are currently no effective treatments for BmNPV, a rapid and simple detection method is urgently needed. This paper describes an electrochemical immunosensor for the detection of BmNPV. The immunosensor was fabricated by covalently immobilizing anti-BmNPV, a biorecognition element, onto the surface of the working gold electrode via 11-mercaptoundecanoic acid (MUA)/ß-mercaptoethanol (ME) hybrid self-assembled monolayers. Electrochemical impedance spectroscopy (EIS) and atomic force microscopy (AFM) were used to characterize the electrochemical performance and morphology of the immunosensor, respectively. Under optimum conditions, the developed immunosensor exhibited a linear response to BmNPV polyhedrin in the range of 1 × 102-1 × 108 fg/mL, with a low detection limit of 14.54 fg/mL. The immunosensor also exhibited remarkable repeatability, reproducibility, specificity, accuracy, and regeneration. Normal silkworm blood was mixed with BmNPV polyhedrin and analyzed quantitatively using this sensor, and the recovery was 92.31 %-100.61 %. Additionally, the sensor was used to analyze silkworm blood samples at different time points after BmNPV infection, and an obvious antigen signal was detected at 12 h post infection. Although this result agreed with that provided by the conventional polymerase chain reaction (PCR) method, the electroanalysis method established in this study was simpler, shorter in detection period, and lower in material cost. Furthermore, this innovative electrochemical immunosensor, developed for the ultra-sensitive and rapid detection of BmNPV, can be used for the early detection of virus-infected silkworms.

Damage to Mitochondria During the Cryopreservation, Causing ROS Leakage, Leading to Oxidative Stress and Decreased Quality of Ram Sperm.

Semen cryopreservation can achieve long-term preservation of sperm. Ice crystal damage, as well as oxidative stress, result in mitochondrial dysfunction and a reduction in sperm motility after thawing. However, limited information exists regarding the impact of reactive oxygen species (ROS) and mitochondria on the cryopreservation of ram sperm. The primary objective of this study was to investigate the relationship between ROS and mitochondria concerning sperm quality during the cryopreservation of ram sperm. This investigation assessed sperm motility, kinematic characteristics, membrane integrity, acrosome integrity, mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) levels, expression of mitochondrial respiratory genes (NDUFV2, SDHA, CYC1, and COXIV), ROS levels, malondialdehyde (MDA) content, phosphatidylserine externalisation rate, sperm ultrastructure, mtDNA copy number, expression of apoptosis-related genes (Bax, Caspase-3, and Caspase-8), Cytochrome C, and Caspase-3 content. The results showed the cryopreservation significantly (p < 0.05) decreased motility, kinetic parameters, membrane integrity, acrosome integrity, MMP, ATP, mRNA expression levels of mitochondrial respiratory-related genes, and significantly (p < 0.05) increased ROS levels, MDA content, phosphatidylserine externalisation rate, damage of sperm ultrastructure, mtDNA copy number, mRNA expression levels of apoptosis-related genes, Cytochrome C and Caspase-3 content compared to the fresh semen group. In conclusion, the cryopreservation causes damage to mitochondria, leading to increased ROS and subsequent oxidative stress. This process also initiates mitochondrial dysfunction and interferes with the electron transport chain, ultimately resulting in decreased MMP and ATP production. Furthermore, the liberation of Cytochrome C prompted the increase in Caspase-3 expression and subsequent sperm apoptosis occurred, ultimately leading to a deterioration in sperm quality after thawing.

Regulation of Fuzheng Huayu capsule on inhibiting the fibrosis-associated hepatocellular carcinogenesis.

In the current study, bioinformatics analysis of the hepatocellular carcinoma (HCC) dataset was conducted with the hepatoprotective effect of the Fuzheng Huayu (FZHY) capsule against the diethylnitrosamine-induced HCC progression analyzed. Eight cell clusters were defined and tanshinone IIA, arachidonic acid, and quercetin, compounds of the FZHY capsule, inhibit HCC progression-related fibrosis by regulating the expression of PLAU and IGFBP3. Combined with the ameliorative effect of the FZHY capsule against liver dysfunctions and expression of PLAU and IGFBP3, our study confirmed the effect of the FZHY capsule on inhibiting the fibrosis-associated HCC progression via regulating the expression of PLAU and IGFBP3.

H2O2 Significantly Affects Larix kaempferi × Larix olgensis Somatic Embryogenesis.

Larch is widely distributed throughout the world and is an important species for timber supply and the extraction of industrial raw materials. In recent years, the hybrid breeding of Larix kaempferi and Larix olgensis has shown obvious heterosis in quick-growth, stress resistance and wood properties. However, its growth and development cycle is too long to meet general production needs. In order to shorten the breeding cycle, we have for the first time successfully established and optimized a somatic embryogenesis system for Larix kaempferi × Larix olgensis. We found that the highest rate of embryonal-suspensor mass (ESM) induction was observed when late cotyledonary embryos were used as explants. The induced ESMs were subjected to stable proliferation, after which abscisic acid (ABA) and polyethylene glycol (PEG) were added to successfully induce somatic embryos. Treatment with PEG and ABA was of great importance to somatic embryo formation and complemented each other's effect. ABA assisted embryo growth, whereas PEG facilitated the formation of proembryo-like structures. On top of this, we studied in more detail the relationship between redox homeostasis and the efficiency of somatic embryogenesis (frequency of ESM induction). During subculture, we observed the gradual formation of three distinct types of ESM. The Type I ESM is readily able to form somatic embryos. In contrast to type I, the type III ESM suffers from severe browning, contains a higher level of hydrogen peroxide (H2O2) and demonstrates a decreased ability to form somatic embryos. External treatment with H2O2 decreased the somatic embryogenesis efficiency of Type I and type III ESMs, or the higher the exogenous H2O2 content, the lower the resulting somatic embryogenesis efficiency. We found that treatment with the H2O2 scavenger DMTU (dimethylthiourea) could significantly increase the somatic embryogenesis efficiency of the type III ESM, as a result of a decline in endogenous H2O2 content. Overall, these findings have contributed to setting up a successful somatic embryogenesis system for larch production.

PSMD12-Mediated M1 Ubiquitination of Influenza A Virus at K102 Regulates Viral Replication.

The M1 of influenza A virus (IAV) is important for the virus life cycle, especially for the assembly and budding of viruses, which is a multistep process that requires host factors. Identifying novel host proteins that interact with M1 and understanding their functions in IAV replication are of great interest in antiviral drug development. In this study, we identified 19 host proteins in DF1 cells suspected to interact with the M1 protein of an H5N6 virus through immunoprecipitation (IP)/mass spectrometry. Among them, PSMD12, a 26S proteasome regulatory subunit, was shown to interact with influenza M1, acting as a positive host factor in IAV replication in avian and human cells. The data showed that PSMD12 promoted K63-linked ubiquitination of M1 at the K102 site. H5N6 and PR8 with an M1-K102 site mutant displayed a significantly weaker replication ability than the wild-type viruses. Mechanistically, PSMD12 promoted M1-M2 virus-like particle (VLP) release, and an M1-K102 mutation disrupted the formation of supernatant M1-M2 VLPs. An H5N6 M1-K102 site mutation or knockdown PSMD12 disrupted the budding release of the virus in chicken embryo fibroblast (CEF) cells, which was confirmed by transmission electron microscopy. Further study confirmed that M1-K102 site mutation significantly affected the virulence of H5N6 and PR8 viruses in mice. In conclusion, we report the novel host factor PSMD12 which affects the replication of influenza virus by mediating K63-linked ubiquitination of M1 at K102. These findings provide novel insight into the interactions between IAV and host cells, while suggesting an important target for anti-influenza virus drug research. IMPORTANCE M1 is proposed to play multiple biologically important roles in the life cycle of IAV, which relies largely on host factors. This study is the first one to identify that PSMD12 interacts with M1, mediates K63-linked ubiquitination of M1 at the K102 site, and thus positively regulates influenza virus proliferation. PSMD12 promoted M1-M2 VLP egress, and an M1-K102 mutation affected the M1-M2 VLP formation. Furthermore, we demonstrate the importance of this site to the morphology and budding of influenza viruses by obtaining mutant viruses, and the M1 ubiquitination regulator PSMD12 has a similar function to the M1 K102 mutation in regulating virus release and virus morphology. Additionally, we confirm the reduced virulence of H5N6 and PR8 (H1N1) viruses carrying the M1-K102 site mutation in mice. These findings provide novel insights into IAV interactions with host cells and suggest a valid and highly conserved candidate target for antiviral drug development.

Photoredox/Nickel Dual-Catalyzed Stereoselective Synthesis of Distal Cyano-Substituted Enamides.

Herein, the efficient photoredox/nickel dual-catalyzed cyanoalkylation reaction of enamides is illustrated. A wide scope of enamides and cycloketone oxime esters was well-tolerated, affording the synthetically versatile and geometrically defined ß-cyanoalkylated enamide scaffolds. The synthetic practicality of this protocol was revealed by gram-scale reactions, further transformations of enamides, and late-stage modifications of biologically active molecules.

Identification of miR-192 target genes in porcine endometrial epithelial cells based on miRNA pull-down.

INTRODUCTION: MicroRNAs (miRNAs)-a class of small endogenous non-coding RNAs-are widely involved in post-transcriptional gene regulation of numerous physiological processes. High-throughput sequencing revealed that the miR-192 expression level appeared to be significantly higher in the blood exosomes of sows at early gestation than that in non-pregnant sows. Furthermore, miR-192 was hypothesized to have a regulatory role in embryo implantation; however, the target genes involved in exerting the regulatory function of miR-192 required further elucidation. METHODS: In the present study, potential target genes of miR-192 in porcine endometrial epithelial cells (PEECs) were identified through biotin-labeled miRNA pull-down; functional and pathway enrichment analysis was performed via gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Bioinformatic analyses were concurrently used to predict the potential target genes associated with sow embryo implantation. In addition, double luciferase reporter vectors, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), and Western blot were performed to verify the targeting and regulatory roles of the abovementioned target genes. RESULTS: A total of 1688 differentially expressed mRNAs were identified via miRNA pull-down. Through RT-qPCR, the accuracy of the sequencing data was verified. In the bioinformatics analysis, potential target genes of miR-192 appeared to form a dense inter-regulatory network and regulated multiple signaling pathways, such as metabolic pathways and the PI3K-Akt, MAPKs, and mTOR signaling pathways, that are relevant to the mammalian embryo implantation process. In addition, CSK (C-terminal Src kinase) and YY1 (Yin-Yang-1) were predicted to be potential candidates, and we validated that miR-192 directly targets and suppresses the expression of the CSK and YY1 genes. CONCLUSION: We screened 1688 potential target genes of miR-192 were screened, and CSK and YY1 were identified as miR-192 target genes. The outcomes of the present study provide novel insights into the regulatory mechanism of porcine embryo implantation and the identification of miRNA target genes.

Comparative study of optical coherence tomograph and histological images of eustachian tube nasopharyngeal region and adjacent structures in vivo and ex-vivo miniature pigs.

OBJECTIVES: Optical Coherence Tomograph (OCT) imaging technology can be used to examine, in vivo, the human ET. At present, it is impossible to achieve the OCT scanning vivo and ex vivo in the same individual human body, or study the consistency between OCT images and histological images of the eustachian tube nasopharyngeal region and adjacent structures. The aim of this study was to determine the consistency between OCT images and histological sections in vivo and ex vivo in miniature pigs. METHODS: OCT imaging was performed on five adult miniature pigs in vivo and ex vivo. The images of the eustachian tube OCT (ET-OCT), nasopharynx OCT (NP-OCT) and histological cross sections were further studied. RESULTS: All five miniature pigs achieved the OCT scan successfully, acquiring ET-OCT and NP-OCT images in vivo and ex vivo on both sides. The acquired ET OCT images closely matched the histological images, revealing details of the cartilage, submucosa, glands, and mucosa. The lower segment of the ET wall mucosa had an abundance of glands and submucosal tissues, with more low-signal areas appearing in the ex vivo images. The NP-OCT images of the nasopharynx matched the details of the mucosa and submucosal tissues. The ex-vivo OCT images showed thicker mucosa and more scattered slightly lower signal areas compared to the vivo OCT images. CONCLUSIONS: ET-OCT images and NP-OCT images matched the histological structure of eustachian tube nasopharyngeal region structures in miniature pigs both in vivo and ex vivo. OCT images may be sensitive to changes in edema and ischemia status. There is a great potential for morphological assessment of inflammation, edema, injure, mucus gland status.

miR-133a-3p regulates the growth of hair follicle stem cells in white goats from the Yangtze River Delta.

The Yangtze River Delta white goats are the sole goat breed producing brush hair of high quality. Owing to the particularities of its wool production, a higher demand is placed on breeding efforts for this animal. Studies on the developmental mechanisms of the aligned hair follicle stem cells (HFSCs) provide a theoretical basis for molecular breeding. In the present study, HFSCs were isolated using the technique of immunohistochemistry from the cervical spinal skin tissue samples from the fetal sheep, and the miR-133a-3p expression was confirmed using quantitative reverse-transcription PCR (RT-qPCR) and western blotting experiments from the isolated HFSCs. Additionally, the effects on the proliferation and apoptosis of HFSCs were detected using flow cytometry and 5-ethynyl-2'-deoxyuridine assays, along with other methods, following the overexpression of miR-133a-3p or its inhibition. The experimental results revealed that miR-133a-3p overexpressed could inhibit the proliferation of HFSCs and promote apoptosis by specifically targeting DUSP6. While the miR-133a-3p knockdown could promote the proliferation but inhibit the apoptosis of the HFSCs. Meanwhile, the miR-133a-3p knockdown experiments showed opposite outcomes. These results illustrate the presence of a relevant network between DUSP6 and miR-133a-3p, which regulates the production of superior-quality brush hair.

Insights into the regulation of MAP3K1 in hair follicle stem cells by transcriptome analysis.

MAP3K1 is a significant member of the MAPK family, and its expressed MEKK1 protein has a wide range of biological activities and is an essential node in the MAPK signaling pathway. A significant number of studies have revealed that MAP3K1 plays a complicated function in the control of cell proliferation, apoptosis, invasion and movement, participates in the regulation of the immune system, and plays an important role in wound healing, tumorigenesis and other processes. In this study, we looked at the involvement of MAP3K1 in the control of hair follicle stem cells (HFSCs). Overexpression of MAP3K1 significantly promoted the proliferation of HFSCs by inhibiting apoptosis and promoting the transition from S phase to G2 phase. The transcriptome identified 189 (MAP3K1_OE) and 414 (MAP3K1_sh) differential genes. The two pathways with the most significant enrichment of differentially expressed genes were the IL-17 signaling pathway and TNF signaling pathway, and the significantly enriched terms in the GO enrichment analysis involved regulation of response of external stimulus, inflammatory and cytokine. Indicate that MAP3K1 can function as a promoting factor in HFSCs through the induction of cell cycle transition from S phase to G2 phase can inhibition apoptosis by mediating crosstalk among several pathways and cytokines.HIGHLIGHTSAbnormal MAP3K1 expression in hair follicle stem cells (HFSCs) can impair HFSC proliferation and apoptosis.MAP3K1 controls hair follicle stem cell proliferation via modulating cell apoptosis and the ratio of cells in S phase/G2 phase.The differential genes shared by MAP3K1_sh and MAP3K1_OE are enriched in GO terms such as inflammation, adipocyte differentiation, acute inflammation, and so on.

DUSP6 inhibits the proliferation of hair follicle stem cells (HFSCs) in vitro.

RNA-seq has shown that the DUSP6 and MAPK signaling pathways are associated with the production of high-quality brush hair (type III hair) in Yangtze River Delta white goats. However, there are few reports on the regulatory effects of DUSP6 expression on hair follicle stem cells (HFSCs) and cellular processes, as well as the underlying mechanism. Here, we investigated the effect of DUSP6 level in HFSCs and the molecular mechanism underlying the functional regulation of HFSCs by DUSP6. Overexpression of DUSP6 significantly suppressed the proliferation of HFSCs by inducing cell cycle arrest in the G1 phase and by promoting apoptosis. Transcriptome analysis revealed a total of 217 differentially expressed genes between DUSP6-overexpressing and control HFSCs, of which 33 (15.2%) were upregulated in DUSP6-overexpressing cells. The two pathways with the most significant enrichment of differentially expressed genes were the TNF signaling pathway and cytokine-cytokine receptor interaction pathway, and the significantly enriched terms in the GO enrichment analysis involved cell attachment and cytokines. These results indicate that DUSP6 can function as an inhibitory factor in HFSCs through the induction of cell cycle arrest in the G1 phase and can promote apoptosis by mediating crosstalk among several pathways and cytokines.HighlightsWe constructed DUSP6 overexpression vectors to detect mRNA and protein expression levels related to high-quality brush hair in MAPK signaling pathway.We found that high expression level of DUSP6 can inhibit the proliferation of hair follicle stem cells (HFSCs) and promote cell apoptosis of HFSCs.DUSP6 may be involved in the growth regulation of HFSCs like Other studies in cancer, tumors by regulating the expression of cytokines, changing the transmission of signals between cells, activating or suppressing immune-related pathways.

Graves' Disease in Children Presenting With Fragility Fracture: A Case Report.

Background: Adults with hyperthyroidism have been found to have decreased bone mineral density (BMD) and higher fracture risk. The most typical cause of hyperthyroidism is Graves' disease. However, there are limited studies on how hyperthyroidism affects bone metabolism and fractures in children. We describe a unique instance of a patient who initially displayed a fragility fracture and was ultimately identified with Graves' disease after biochemical evaluations. Case Summary: A 2-year-8-month-old female presented with fragility fractures three times in only 7 months. A series of examinations were performed to evaluate any possible malformations or abnormalities of bone metabolism. Graves' disease was found, and drug therapies were employed (methimazole, propranolol, calcium carbonate, vitamin D). Since children with Graves' disease and fragility fractures have been uncommonly described in the past, a stringent and thorough long-term follow-up was initiated. Conclusions: Children with undiagnosed Graves' disease had a higher risk of fractures and osteoporosis. This case suggests that BMD measurement may be necessary for the initial evaluation of Graves' disease in children.

Molecular Characterization and Function of the Nogo-66 Receptor (NgR1) Gene in the Chinese Tree Shrew.

BACKGROUND: Nogo-66 receptor (NgR1) is a glycosylphosphatidylinositol-linked cell surface receptor with high affinity for Nogo-66. The binding of Nogo-66 to NgR1 plays a key role in inhibiting neurite growth, limiting synaptic plasticity and mediating Mammalian Reovirus (MRV) infection. The Chinese tree shrew (Tupaia belangeri chinensis) is, a new and valuable experimental animal that is widely used in biomedical research. Although susceptible to MRV, little is known about tree shrew NgR1 and its role in MRV infection. METHODS: In this study, we cloned NgR1 form the Chinese tree shrew by RACE technology and analyzed its characteristics, spatial structure and its tissue expression. We also examined the expression pattern of NgR1 in the response of tree shrew primary nerve cells (tNC) to MRV1/TS/2011 infection. RESULTS: Tree shrew NgR1 was found to have a closer relationship to human NgR1 (90.34%) than to mouse NgR1. Similar to the protein structure of human NgR1, the tree shrew NgR1 has the same leucine-rich repeat (LRR) domain structure that is capped by C-terminal and N-terminal cysteine-rich modules. The tree shrew NgR1 mRNAs were predominantly detected in the central nervous system (CNS), and tree shrew NgR1 can mediate infection by MRV1/TS/2011. CONCLUSIONS: Taken together, these results help to elucidate the function of NgR1 and provide a basis for using the tree shrew as an animal model for studies of the nervous system and infectious diseases.

Effects of different management practices on soil microbial community structure and function in alpine grassland.

Management practices, such as grazing exclusion and reseeding, have been implemented to mitigate the degradation of grassland. Low grazing intensities and reseeding increase grass production. Nevertheless, few studies have investigated the effects of these measures on the soil microbial community structure and function in the Qinghai Tibetan Plateau (QTP). To reveal the effects of management practices on soil microbes and give a reference to assess and improve ecosystems functions, we here evaluated the impact of various types of grazing (exclusion, seasonal, and traditional), reseeding (annual oat (Avena fatua) grassland (RO) and perennial artificial grassland cultivated >10 y), and integrated restoration (weed control and no-tillage reseeding) measures on soil microbial community structure and function in the QTP. The Shannon-Wiener diversity indices were highest for prokaryotes under RO and for fungi under integrated grassland restoration. Relative Actinobacteria abundance was higher under seasonal grazing than that under integrated grassland restoration. The latter had relatively higher abundances of Betaproteobacteria, Alphaproteobacteria, and Deltaproteobacteria and comparatively lower abundance of Thermoleophilia. There were significantly higher abundances of plant pathogens under seasonal grazing than those under other managements. There were significantly high proportions of pathotrophs and saprotrophs (10.0%) under seasonal and traditional grazing, respectively. The proportion of pathotrophs under integrated restoration (10.0%) was about seven-fold greater than that under grazing exclusion (1.5%). The relative differences among treatments in terms of soil water content, plant biomass, and soil C:N partially explained the differences in their prokaryotic community compositions. Increases in soil organic carbon and C:N may explain the observed changes in the soil fungal communities. The management practices affected soil microorganisms mainly by altering the soil nutrient profile. Grazing attracted specific pathotrophs and saprotrophs while repelling certain plant pathogens. Hence, modulations in soil microbial community structure and function must be considered in the process of planning for the implementation of grassland degradation management measures.