Integration Analysis of Hair Follicle Transcriptome and Proteome Reveals the Mechanisms Regulating Wool Fiber Diameter in Angora Rabbits.

Fiber diameter is an important characteristic that determines the quality and economic value of rabbit wool. This study aimed to investigate the genetic determinants of wool fiber diameter through an integration analysis using transcriptomic and proteomic datasets from hair follicles of coarse and fine wool from Angora rabbits. Using a 4D label-free technique, we identified 423 differentially expressed proteins (DEPs) in hair follicles of coarse and fine wool in Angora rabbits. Eighteen DEPs were examined using parallel reaction monitoring, which verified the reliability of our proteomic data. Functional enrichment analysis revealed that a set of biological processes and signaling pathways related to wool growth and hair diameter were strongly enriched by DEPs with fold changes greater than two, such as keratinocyte differentiation, skin development, epidermal and epithelial cell differentiation, epidermis and epithelium development, keratinization, and estrogen signaling pathway. Association analysis and protein-protein interaction network analysis further showed that the keratin (KRT) family members, including KRT77, KRT82, KRT72, KRT32, and KRT10, as well as CASP14 and CDSN, might be key factors contributing to differences in fiber diameter. Our results identified DEPs in hair follicles of coarse and fine wool and promoted understanding of the molecular mechanisms underlying wool fiber diameter variation among Angora rabbits.

Facile Construction of Benzo[d][1,3]oxazocine: Reductive Radical Dearomatization of N-Alkyl Quinoline Quaternary Ammonium Salts.

Reductive radical dearomatization N-alkyl quinoline quaternary ammonium salts to synthesize structurally complex and challenging polysubstituted benzo[d][1,3]oxazocines was first reported. The mechanism showed various allyl alcohols can be converted into alkyl radicals under reduction conditions of iron/silane. These radicals then nucleophilically attack the C4 site of N-alkyl quinoline quaternary ammonium salts, and intramolecular cyclization of the resulting intermediate generates the target product. This method not only produced a series of novel polysubstituted benzo[d][1,3]oxazocines but also prepared polycyclic benzo[d][1,3]oxazocines. Finally, this strategy made up for the lack of reductive radical reports on N-alkylquinolinium salts and also had the advantages of mild reaction conditions, wide substrate range, and novel product structure.

Access to 5-Methyl-5H-naphtho[2,3-c]carbazole-8,13-dione Derivatives via Copper-Catalyzed Intramolecular Isomerization.

Carbazole-fused quinones are important compounds for their potential pharmacological activities and photophysical properties. Here, a novel copper-catalyzed intramolecular isomerization process to access a new class of naphtho[2,3-c]carbazole-8,13-dione derivatives via a furan isomerization/γ-H elimination and ß-C elimination/6π-electrocyclization/aromatization cascade is reported. Furthermore, the preliminary photophysical properties of the functional 5-methyl-5H-naphtho[2,3-c]carbazole-8,13-dione derivatives have been studied.

Effects of Inherent Minerals on Pyrolysis Behavior and Kinetics of Jimsar Oil Shale.

In order to reveal the influences of different inherent minerals on the pyrolysis behavior and kinetics of oil shale, decarburization, and desilication, samples were obtained by pickling and demineralization. The influence of inherent minerals on the activation energy of oil shale at different conversion rates and the pyrolysis kinetic model were researched by the equal conversion method and principal curve method. The results demonstrated that the average and maximum weight loss rates and volatile release characteristic index of JM-C were lower than that of JM-R; however, JM-S appeared with the opposite trend. At the initial stage (α = 0.2-0.6), the pyrolysis activation energy of JM-C was basically the same as that of JM-R, while the pyrolysis activation energy of JM-S decreased. At the later stage (α = 0.6-0.8), the pyrolysis activation energy of JM-C was higher than that of JM-R, while the activation energy of JM-S was between JM-C and JM-R. The existence of inherent carbonates reduced the pyrolysis activation energy of oil shale, but only at the later stage of pyrolysis. In addition, the existence of inherent carbonates changed the pyrolysis kinetic model of oil shale from an order model to a one-dimensional diffusion model, encompassing f(α) = (1 - α)2.5 and f(α) = 0.5α-1. However, the existence of inherent silicates increased the activation energy of oil shale pyrolysis. Moreover, its mechanism was consistent with the original model, namely, an order model, f(α) = 1 - α.

Transcriptome analysis of divergent residual feed intake phenotypes in the M. longissimus thoracis et lumborum of Wannan Yellow rabbits.

Introduction: Feed efficiency is an important economic trait in rabbit meat production. The identification of molecular mechanisms and candidate genes for feed efficiency may improve the economic and environmental benefits of the rabbit meat industry. As an alternative to the conventional feed conversion ratio, residual feed intake (RFI) can be used as an accurate indicator of feed efficiency. Methods: RNA sequencing was used to identify the differentially expressed genes (DEGs) in the M. longissimus thoracis et lumborum of eight Wannan Yellow rabbits with excessively high or low RFIs (HRFI or LRFI, respectively). Thereafter, Gene Ontology (GO) analysis, enrichment using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, gene set enrichment analysis (GSEA), and protein-protein interaction (PPI) network analysis was conducted. Results: In total, 445 DEGs were identified in the M. longissimus thoracis et lumborum of rabbits with high and low RFIs. The significantly enriched GO terms identified in these two groups were primarily involved in energy and mitochondrial metabolism and oxidation-reduction processes. KEGG analysis identified 11 significantly enriched pathways, including oxidative phosphorylation, PI3K-Akt signaling, and extracellular matrix-receptor interaction pathways. According to GSEA, the expressions of genes and pathways related to mitochondrial function were upregulated in HRFI rabbits, whereas genes with upregulated expressions in LRFI rabbits were related to immune response and energy metabolism. Additionally, PPI network analysis revealed five potential candidate genetic markers. Conclusion: Comparative analysis of the M. longissimus thoracis et lumborum transcriptomes in HRFI and LRFI rabbits revealed FOS, MYC, PRKACB, ITGA2, and FN1 as potential candidate genes that affect feed efficiency in rabbits. In addition, key signaling pathways involved in oxidative phosphorylation and PI3K-Akt and ECM-receptor interaction signaling impact rabbit feed efficiency. These findings will aid in breeding programs to improve feed efficiency and optimize RFI selection of rabbits for meat production.

Semen quality and seminal plasma metabolites in male rabbits (Oryctolagus cuniculus) under heat stress.

Heat stress causes infertility in male rabbits in summer. This study was conducted to determine the effects of heat stress on semen quality and seminal plasma metabolites of male rabbits. To achieve these objectives, the temperature and humidity index (THI) was used to determine the stress state of male rabbits during different months, thereby the rabbits were divided into heat stress and no heat stress groups. The quality of the semen and the biochemical indices of seminal plasma were then analyzed. Next the plasma metabolites of rabbits in both groups were evaluated using the ultra-high performance liquid chromatography-mass spectroscopy (UPLC-MS)/MS technique. Our results showed that the THI value of the rabbit housing in May was 20.94 (no heat stress). The THI value of the housing in August was 29.10 (heat stress group, n = 10). Compared with the non-heat stress group, the sperm motility, density, and pH in the heat stress group (n = 10) were significantly decreased (P < 0.01); the semen volume decreased significantly (P < 0.05); and the sperm malformation rate increased significantly (P < 0.01). The number of grade A sperm significantly decreased, while the numbers of B and C grade sperm significantly increased (P < 0.01). The total sperm output (TSO), total motile sperm (TMS), and total functional sperm fraction (TFSF) decreased significantly (P < 0.01). Heat stress protein 70 (HSP70) and acid phosphatase (ACP) in the seminal plasma of rabbits in the heat stress group (n = 20) were significantly increased (P < 0.01). Seminal plasma testosterone (T), α-glucosidase (α-Glu), and fructose decreased significantly (P < 0.01). The concentrations of Mg2+ (P < 0.05), Na+ (P < 0.01), and K+ (P < 0.01) in metal ions were significantly decreased. These findings indicated that heat stress severely affected the quality of the male rabbit semen. Furthermore, UPLC-MS/MS technology was used to analyze the seminal plasma samples of rabbits in the heat stress group and non-heat stress group (n = 9 for each group). In total, 346 metabolites were identified, with variable importance in project (VIP) > 1.0, fold change (FC) > 1.5 or < 0.667, and P < 0.05 as the threshold. A total of 71 differential metabolites were matched, including stearic acid, betaine, arachidonic acid, L-malic acid, and indole. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of differential metabolites revealed 51 metabolic pathways, including synthesis and degradation of ketones, serine and threonine metabolism, tryptophan metabolism, and the citric acid cycle. Our study has shown that the sperm motility, sperm pH value, and sperm density of male rabbits decreased significantly under heat stress, and the sperm malformation rate increased significantly. Furthermore, the quality of semen was shown to deteriorate and the energy metabolism pathway was disturbed. These findings provide a theoretical reference for alleviating the adaptive heat stress in male rabbits.

Deleting specific residues from the HNH linkers creates a CRISPR-SpCas9 variant with high fidelity and efficiency.

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR-associated (Cas) systems are immunological defenses used in archaea and bacteria to recognize and destroy DNA from external invaders. The CRISPR-SpCas9 system harnessed from Streptococcus pyogenes (SpCas9) has become the most widely utilized genome editing tool and shows promise for clinical application. However, the off-target effect is still the major challenge for the genome editing of CRISPR-SpCas9. Based on analysis of the structure and cleavage procedures, we proposed two strategies to modify the SpCas9 structure and reduce off-target effects. Shortening the HNH or REC3 linkers (Strategy #1) aimed to move the primary position of HNH or REC3 far away from the single-guide RNA (sgRNA)/DNA hybrid (hybrid), while elongating the helix around the sgRNA (Strategy #2) aimed to strengthen the contacts between SpCas9 and the sgRNA/DNA. We designed 11 SpCas9 variants (variant No.1- variant No.11) and verified their efficiencies on the classic genome site EMX1-1, EMX1-1-OT1, and EMX1-1-OT2. The top three effective SpCas9 variants, variant No.1, variant No.2, and variant No.5, were additionally validated on other genome sites. The further selected variant No.1 was compared with two previous SpCas9 variants, HypaCas9 (a hyper-accurate Cas9 variant released in 2017) and eSpCas9 (1.1) (an "enhanced specificity" SpCas9 variant released in 2016), on two genome sites, EMX1-1 and FANCF-1. The results revealed that the deletion of Thr769 and Gly906 could substantially decrease off-target effects, while maintaining robust on-target efficiency in most of the selected genome sites.

MAX transcriptionally enhances PD-L1 to inhibit CD8+ T cell-mediated killing of lung adenocarcinoma cells.

Immune checkpoint blockade (ICB) therapies, such as monoclonal antibodies against the PD-1/PD-L1 immune checkpoint pathway, have been a major breakthrough in the treatment of lung cancer especially lung adenocarcinoma (LUAD), but their effectiveness is limited. High expression of PD-L1 in tumor cells is one of the key reasons evading immune surveillance, yet the mechanisms that regulate PD-L1 expression are not fully understood. By analyzing the chromatin immunoprecipitation sequencing data of MYC-associated X-factor (MAX) based on lung cancer cell lines, we found that the transcriptional regulator MAX is able to bind to the promoter region of the PD-L1 gene. Further, we performed several molecular biology experiments to determine that MAX promotes PD-L1 transcription in LUAD cells, which in turn assists LUAD cells to evade killing by CD8+ T cells, an effect that can be reversed by anti-PD-L1 antibody. In LUAD, the expression of MAX is positively correlated with PD-L1 and the infiltration of CD8+ T cells. Importantly, we further identified that high expression of the MAX/PD-L1 axis is associated with poor overall survival and fist progression of patients with LUAD. Thus, this study sheds light on the mechanism by which MAX inhibits CD8+ T cell-mediated killing of LUAD cells by activating PD-L1 transcription, and MAX may serve as a potential combinatorial target for ICB therapies that block the PD-1/PD-L1 pathway in LUAD.

Hair Follicle Transcriptome Analysis Reveals Differentially Expressed Genes That Regulate Wool Fiber Diameter in Angora Rabbits.

Wool fiber diameter (WFD) is an important index of wool traits and the main determinant of wool quality and value. However, the genetic determinants of fiber diameter have not yet been fully elucidated. Here, coarse and fine wool of Wan strain Angora rabbits and their hair follicle traits were characterized. The results indicated significant differences in the diameters of wool fibers and their hair follicles. The RNA sequencing (RNA-Seq) technique was used to identify differences in gene expression in hair follicles between coarse and fine wool. In total, 2574 differentially expressed genes (DEGs) were found between the two hair follicle groups. Transcription factors, keratin-associated protein (KAP) and keratin (KRT) families, and ECM-related genes may control the structure of fine fibers in rabbits. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that skin development, epidermal cell and keratinocyte differentiation, epithelium development, and Notch and ribosome signaling pathways were significantly enriched, respectively. GSEA further filtered six important pathways and related core genes. PPI analysis also mined functional DEGs associated with hair structure, including LEF1, FZD3, SMAD3, ITGB6, and BMP4. Our findings provide valuable information for researching the molecular mechanisms regulating wool fiber and could facilitate enhanced selection of super-fine wool rabbits through gene-assisted selection in the future.

Bovine colostrum promoted ileal health in newborn lambs at 24 h after birth: insight from intestinal morphology and innate immunity.

The contribution of colostrum to passive immunity transfer and intestinal protection in newborn ruminants is well known; however, it is currently unclear how colostrum intake affects intestinal innate immunity. We investigated the effects of bovine colostrum intake on ileal morphology, expression of genes involved in intestinal innate immunity, and serum concentrations of inflammatory cytokines in newborn lambs. Twenty-seven newborn male Hu lambs were used, of which 18 were bottle-fed either bovine colostrum (C24h; n = 9) or bovine mature milk (M24h; n = 9) within the first 2 h after birth at an intake of approximately 8% of BW; the remaining nine lambs did not receive any feeding (N24h). Blood and ileal tissue samples were collected after the lambs were slaughtered at 24 h after birth. Ileal villus height and villus height-to-crypt depth ratio were significantly higher in C24h than those in N24h and M24h lambs (P < 0.01). Messenger RNA (mRNA) abundance of toll-like receptor (TLR)-2, TLR3, TLR4, TLR6, TLR7, TLR8 and tumour necrosis factor alpha in the ileum was lower in C24h than that in N24h lambs (P < 0.05). Moreover, C24h lambs had a lower TLR3 mRNA abundance (P < 0.01) and a trend of lower TLR6 (P = 0.06) and interleukin 1 beta (P = 0.08) expression compared with those in M24h lambs. We also observed strong positive correlations of tumour necrosis factor alpha expression with that of TLR2 (r = 0.71; P < 0.001), TLR4 (r = 0.88; P < 0.001) and TLR8 (r = 0.83; P < 0.001). Interestingly, the expression of barrier-related molecules, including mucin-13, lysozyme, claudin (CLDN)-1, CLDN2, CLDN4, CLDN7, CLDN12, occludin, zonula occluden-1 and junctional adhesion molecule-1, was consistently lower in C24h lambs than that in N24h and M24h lambs (P < 0.05). These results indicated that the beneficial roles of colostrum intake on intestinal protection in newborn lambs were associated with low TLR expression, which was reflected by improved intestinal development and reduced inflammatory response. Further studies using fluorescence in situ hybridisation and immunohistochemical methods are needed to further explore the mechanisms underlying the lower expression of intestinal barrier-related molecules due to colostrum feeding.

"One body and two wings" novel nanozyme combined with photothermal therapy for Combat Drug-Resistant Bacteria.

Bacterial resistance caused by antibiotic therapy is a serious problem. Therefore, there is an urgent need to find alternative methods to overcome bacterial resistance. Herein, we synthesized a new type of iridium oxide (IrOx) as an alternative to antibiotics. Iridium oxide not only has good catalytic properties, but also has photothermal properties, and then realizes the "one body and two wings" strategy to enhance the antibacterial effect. Research results show that near-infrared light can enhance the peroxidase catalytic activity of IrOx and generate highly toxic hydroxyl radicals (·OH) by catalyzing hydrogen peroxide (H2O2). Hydroxyl radicals have a high redox potential, which can overcome the drug resistance of gram-positive and negative bacteria. Importantly, IrOx has no obvious cellular and in vivo toxicity. Accordingly, the novel photothermal nanozyme is expected to be applied to bacterial infectious diseases, such as wound healing, sepsis, and implant-related infections.

LINC00205 Promotes Tumor Malignancy of Lung Adenocarcinoma Through Sponging miR-185-5p.

The emerging role of long noncoding RNAs (lncRNAs) in cancer, especially in lung adenocarcinoma (LUAD), is attracting increasingly more attention as a potential therapeutic target. However, whether lncRNA LINC00205 regulates the malignancy of LUAD has not been characterized. In this study, we discovered that LINC00205 was markedly upregulated in LUAD tissues and cell lines and correlated with poor prognosis of patients with LUAD. Our data showed that LINC00205 promoted the migration and proliferation of LUAD cells in vitro and tumor growth in vivo. Notably, the tumor suppressor miR-185-5p was found to be a direct target of LINC00205. In addition, miR-185-5p diminished the promotion of cell proliferation and migration mediated by LINC00205, whereas miR-185-5p inhibition had the opposite effect. In summary, our results show that LINC00205 contributes to LUAD malignancy by sponging miR-185-5p, which provides new insight into LUAD progression.

Analysis of histology and long noncoding RNAs involved in the rabbit hair follicle density using RNA sequencing.

BACKGROUND: Hair follicle density influences wool fibre production, which is one of the most important traits of the Wan Strain Angora rabbit. However, molecular mechanisms regulating hair follicle density have remained elusive. RESULTS: In this study, hair follicle density at different body sites of Wan Strain Angora rabbits with high and low wool production (HWP and LWP) was investigated by histological analysis. Haematoxylin-eosin staining showed a higher hair follicle density in the skin of the HWP rabbits. The long noncoding RNA (lncRNA) profile was investigated by RNA sequencing, and 50 and 38 differentially expressed (DE) lncRNAs and genes, respectively, were screened between the HWP and LWP groups. A gene ontology analysis revealed that phospholipid, lipid metabolic, apoptotic, lipid biosynthetic, and lipid and fatty acid transport processes were significantly enriched. Potential functional lncRNAs that regulate lipid metabolism, amino acid synthesis, as well as the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and hedgehog signalling pathways, were identified. Consequently, five lncRNAs (LNC_002171, LNC_000797, LNC_005567, LNC_013595, and LNC_020367) were considered to be potential regulators of hair follicle density and development. Three DE lncRNAs and genes were validated by quantitative real-time polymerase chain reaction (q-PCR). CONCLUSIONS: LncRNA profiles provide information on lncRNA expression to improve the understanding of molecular mechanisms involved in the regulation of hair follicle density.

Comparative proteomic characterization of bovine milk containing ß-casein variants A1A1 and A2A2, and their heterozygote A1A2.

BACKGROUND: Genetic variants of ß-casein are cosnidered to affect the components of milk. However, limited data are available on the bovine protein components correlated with ß-casein variants at the proteome level. In the present study, cows producing milk containing ß-casein variants (A1A1 and A2A2) and their heterozygote (A1A2) were identified using a high-resolution melting method, and milk samples were collected and tested. Comparative analyses of casein micelles, whey and milk fat globule membrane fractions in each milk variant were performed using a label-free proteomics approach. RESULTS: The results obtained showed that ceruloplasmin and cathelicidin-2 were the most abundant proteins in milk containing variant A1A1; lactoferrin and CD5 molecule-like were the most abundant proteins in milk containing variant A2A2; and selenoprotein P and osteopontin were the most abundant proteins in milk containing heterozygote A1A2. Differences in protein components in milk containing the different ß-casein variants were visualized using hierarchical clustering, and profiles were separated using principal components analysis. The differentially expressed proteins in milk containing A1A1, A2A2 or A1A2 were predominantly involved in response to stress and defense response according to their Gene Ontology annotations. CONCLUSION: Our findings provide new insights into differentially expressed milk proteins corresponding to the presence of different ß-casein variants. This knowledge will help determine their potential biological functions in dairy products and the effects on human health. © 2020 Society of Chemical Industry.

Pregnancy with giant ovarian dysgerminoma: A case report and literature review.

RATIONALE: Dysgerminoma is an extraordinarily rare neoplasm arising from the malignant germ cells of the ovary. Early antenatal diagnosis and proper management of the neoplasm to improve maternal-neonatal results are the considerable challenges facing the gyne-oncologist. We summarize the clinical features and discuss treatment strategies of the ovary dysgerminoma (OD). Besides, we also review the literature on OD in PubMed, Web of Science Core Collection, Library of Congress, and LISTA from 1939 to 2019 to evaluate its clinical characteristics, feto-maternal compromise, management, and fertility outcome. PATIENT CONCERNS: A 25-year-old pregnant woman reported lower abdominal pain and vomiting. DIAGNOSIS: The patient was diagnosed as right OD. INTERVENTIONS: She received a cesarean section due to severe abdominal pain, delivered a healthy girl at 38 C 4 weeks of gestation, and accepted fertility-preserving surgery. However, the patient refused chemotherapy postoperatively. OUTCOMES: The patient was followed up 42 days, 3 months, and 6 months after surgery, and no tumor recurrence was observed. LESSONS: OD has non-specificity characteristics, including age, symptoms, image date, and tumor marks. However, these abnormal indicators may provide some evidence for accurate antenatal diagnosis. The management strategies should be considered comprehensively on an individual basis, and fertility-preserving surgery should be carried out in the second trimester if further pregnancy is desired. Adjuvant chemotherapy needs to be applied to the treatment of OD patients with The International Federation of Gynecology and Obstetrics (FIGO) stages II, III, and IV and timely chemotherapy is suggested if there are several weeks before the expected date of delivery. The overall prognosis of OD patients is excellent.

Primary ovarian carcinoid: Two cases report and review of literature.

INTRODUCTION: Carcinoid tumor is one of the most frequent neuroendocrine tumors, and the majority of which are usually observed in the lungs and gastrointestinal tract. The prevalence of ovarian carcinoids is merely 0.1% in ovarian neoplasms and 1% in carcinoid tumors. We described 2 rare cases in our hospital of primary ovarian carcinoid (POC), causing carcinoid syndrome (CS) of the diarrhea, constipation, and carcinoid heart disease. Besides, we also reviewed related literatures about its origin, variant, clinical manifestation, diagnosis methods, pathological features, treatment strategies and prognosis from 2009 to 2019. PATIENT CONCERNS: Case 1 was a 61-year-old postmenopausal woman and presented with diarrhea, abdominal pain, enlargement, bloating and dizziness. Case 2 was a 49-year-old patient who complained of constipation, abdominal pain, bloating, and headache. DIAGNOSIS: Both patients were diagnosed as primary ovarian carcinoid, insular type. INTERVENTIONS: Total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), omentectomy, pelvic lymphadenectomy, and appendectomy without chemotherapy were performed in case 1. Cervix resection, right salpingo-oophorectomy, appendectomy, and pelvic lesion resection with chemotherapy was conducted in case 2. OUTCOMES: Both patients achieved satisfactory treatment effects. The follow-up period was 18 and 17 months in case 1 and case 2, respectively. Case 1 encountered carcinoid heart disease and received percutaneous transluminal coronary angioplasty (PTCA) postoperatively. Case 2 suffered multiple metastases postoperatively. However, after effective treatment, both patients were in good condition during follow-up duration. CONCLUSION: POC is an extraordinarily rare disease, and commonly with a satisfactory outcome. TAH+BSO with or without postoperative chemotherapy has been considered as an acceptable treatment strategy for POC patients.

Analysis of histological and microRNA profiles changes in rabbit skin development.

The periodic regrowth of rabbit fur is economically important. Here, we aimed to characterise the histological traits and microRNA (miRNA) expression profiles in the skin tissue of Wan Strain Angora rabbits at different weeks after plucking. Haematoxylin-eosin staining showed that hair follicles were in the telogen phase in the first week, while they were in the anagen phase from the fourth to twenty-fourth weeks. In addition, two small RNA libraries derived from skin samples of Wan Strain Angora rabbits at telogen and anagen stages yielded over 24 million high-quality reads. Specifically, 185 miRNAs were differentially expressed between the telogen and anagen phases. The function of the differentially expressed miRNAs was explored by comparing them with known mammalian miRNAs and by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis of their predicted targets. Five new functional miRNAs were validated using quantitative real-time PCR. Moreover, the fibroblast growth factor 5 (FGF5) gene was verified to be a target of conservative_NC_013672.1_9290 and conservative_NC_013675.1_10734. We investigated differential miRNA profiles between the telogen and anagen phases of the hair cycle and our findings provide a basis for future studies focusing on the mechanisms of miRNA-mediated regulation of rabbit hair follicle cycling.

PMS2 germline mutation c.1577delA (p.Asp526Alafs*69)-induced Lynch syndrome-associated endometrial cancer: A case report.

RATIONALE: Lynch syndrome (LS) is an autosomal dominant cancer predisposition condition caused by germline heterozygous mutations in mismatch repair (MMR) genes. However, as one of the MMR genes, PMS2 mutation-induced LS-associated endometrial cancer (LSAEC) was rarely reported. PATIENT CONCERNS: A 26-year-old female patient suffered from prolonged menstrual period and increased menstrual flow for 2 months. DIAGNOSES: The patient was diagnosed with cervix CIN III, endometrial cancer (EC), anemia, and LS. INTERVENTIONS: Total hysterectomy, bilateral salpingectomy, pelvic lymphadenectomy were performed for treating EC, while ovariectomy was refused by the patient. The patient underwent postoperative chemotherapy with paclitaxel combined with carboplatin for 6 courses of treatment. Laparoscopic partial enterectomy was applied for treating colon cancer 5 years later after the surgery treatment for EC. Besides, Sanger sequencing and high-throughput genome sequencing were employed to detect the genetic status of the family that included two generations with four members. Immunohistochemistry (IHC) staining was used to identify the function of PMS2 mutation. OUTCOMES: The 26-year-old Chinese patient suffered from LSAEC and recovered well after surgery. A PMS2 germline heterozygous mutation (c.1577delA) was confirmed by gene sequencing 5 years later. In addition, PMS2 mutation was verified by IHC. The patient was followed up for 7 years. LESSONS: Carrying PMS2 germline mutation (c.1577delA) confers an extremely high susceptibility of suffering from LS-associated cancers. Thus, close clinical monitoring and prophylactic surgery are highly recommended to reduce the morbidity and mortality of LS-associated cancers.

miRNA-344b-1-3p modulates the autophagy of NR8383 cells during Aspergillus fumigatus infection via TLR2.

Autophagy serves a pivotal role in host defense during fungal infections, and the contribution by toll-like receptor 2 (TLR2) has been well demonstrated. It has been reported that microRNA-344a-1-3p (miR-344a-1-3p) can directly target TLR2. However, the expression of TLR2 significantly decreases during Aspergillus fumigatus infection. Therefore, the specific role of miR-344a-1-3p in the host defense against A. fumigatus infection remains to be elucidated. In the present study, A. fumigatus infection increased the expression of TLR2 and induced autophagy, which was indicated by increasing expression levels of autophagy-related protein 5 (ATG5), Beclin-1, light chain 3 (LC3)-1 and LC3-II, as measured by western blot analysis, and an increased number of GFP-LC3 puncta, as measured by fluorescence. Following transfection with miR-344a-1-3p mimics and/or TLR2, miR-344b-1-3p significantly inhibited the expression of TLR2, Beclin-1, ATG5, LC3-I and LC3-II, whereas the overexpression of TLR2 significantly attenuated the inhibitory effect on autophagy by miR-344b-1-3p. Collectively, these findings demonstrate that A. fumigatus can be controlled by the induction of autophagy following de-repression of the expression of TLR2, mediated by miR-344a-1-3p.

Analyses of histological and transcriptome differences in the skin of short-hair and long-hair rabbits.

BACKGROUND: Hair fibre length is an important economic trait of rabbits in fur production. However, molecular mechanisms regulating rabbit hair growth have remained elusive. RESULTS: Here we aimed to characterise the skin traits and gene expression profiles of short-hair and long-hair rabbits by histological and transcriptome analyses. Haematoxylin-eosin staining was performed to observe the histological structure of the skin of short-hair and long-hair rabbits. Compared to that in short-hair rabbits, a significantly longer anagen phase was observed in long-hair rabbits. In addition, by RNA sequencing, we identified 951 genes that were expressed at significantly different levels in the skin of short-hair and long-hair rabbits. Nine significantly differentially expressed genes were validated by quantitative real-time polymerase chain reaction. A gene ontology analysis revealed that epidermis development, hair follicle development, and lipid metabolic process were significantly enriched. Further, we identified potential functional genes regulating follicle development, lipid metabolic, and apoptosis as well as important pathways including extracellular matrix-receptor interaction and basal cell carcinoma pathway. CONCLUSIONS: The present study provides transcriptome evidence for the differences in hair growth between short-hair and long-hair rabbits and reveals that lipid metabolism and apoptosis might constitute major factors contributing to hair length.