Chronic progressive external ophthalmoplegia (CPEO) is a classical mitochondrial ocular disorder characterized by bilateral progressive ptosis and ophthalmoplegia. Kearns -Sayre syndrome (KSS) is a multisystem disorder with PEO, cardiac conduction block, and pigmentary retinopathy. A few individuals with CPEO have other manifestations of KSS, but do not meet all the clinical diagnosis criteria, and this is called "CPEO plus."

Polymer nanoparticles modified with collagen peptides (CPs) are an attractive strategy for the oral delivery of active ingredients from Chinese medicine. Thus, in the present study, collagen cationic CPs were simply separated using ion-exchange resin from bovine CPs, to modify mixed nanomicelles (MMs) on the surface to improve the oral bioavailability of Cucurbitacin B (CuB). The physicochemical property of micelles was characterized, which confirmed the successful modification of the nanomicelles. CPs-modified nanomicelles in vitro were found to significantly increase cellular uptake and transportation. Compared to unmodified micelles, the quantity of CPs-modified micelles internalized by Caco-2 cells were 3.74 times greater and the cumulative transportation flux (AP-BL) was 2.81 times greater. The membrane transportation process of CuB-MMs-CPs was found to be associated with energy consumption and clathrin- and caveolin-mediated endocytosis. In vivo studies performed on rats indicated that in comparison to CuB and CuB-MMs, the relative bioavailability of CuB-MMs-CPs increased by 3.43 times and 2.14 times, respectively. In addition, the tumor inhibition caused by CuB-MMs-CPs was increased significantly. Therefore, the nanomicelles co-modified with isolated CPs could act as attractive carriers for oral delivery of CuB.

Root-knot nematodes, Meloidogyne spp., cause considerable damage in eggplant production. Transferring of resistance genes from wild relatives would be valuable for the continued improvement of eggplant. Solanum aculeatissimum, a wild relative of eggplant possessing resistance to Meloidogyne incognita, is potentially useful for genetically enhancing eggplant. In the present study, we have isolated and characterized a nucleotide-binding site leucine-rich repeat (NBS-LRR) resistance gene, designated as SacMi. The full-length cDNA of the SacMi gene was obtained using the technique of rapid-amplification of cDNA ends (RACE). The open reading frame of the SacMi gene was 4014 bp and encoded a protein of 1338 amino acids. Sequence analysis indicated that SacMi belong to the non- Toll/Interleukin-1 receptor (TIR)-NBS-LRR type disease-resistance genes. Interestingly, quantitative RT-PCR showed that SacMi is expressed at low levels in uninfected roots, but was up-regulated by infection with M. incognita. To investigate the role of SacMi in S. aculeatissimum resistance against M. incognica, the tobacco rattle virus (TRV)-mediated virus-induced gene silencing (VIGS) system was used. Silencing of SacMi enhanced susceptibility of S. aculeatissimum plants to M. incognita, suggesting the possible involvement of SacMi in resistance against M. incognita infection.

Assessing the potential effects of insect-resistant genetically engineered (GE) plants on collembolans is important because these common soil arthropods may be exposed to insecticidal proteins produced in GE plants by ingestion of plant residues, crop pollen, or root exudates. Laboratory studies were conducted to evaluate the potential effects of two Bacillus thuringiensis (Bt)-rice lines expressing Cry1C and Cry2A in pollen and leaves and of their non-Bt conventional isolines on the fitness of the collembolan Folsomia candida and on the activities of its antioxidant-related enzymes, superoxide dismutase and peroxidase, and of its detoxification-related enzymes, glutathione reductase and glutathione S-transferase. Survival, development, reproduction, and the intrinsic rate of increase (rm) were not significantly reduced when F. candida fed on the Bt rice pollen or leaf powder than on the non-Bt rice materials; these parameters, however, were significantly reduced when F. candida fed on non-Bt rice pollen or non-Bt leaf-based diets containing the protease inhibitor E-64 at 75 μg/g. The activities of the antioxidant-related and detoxification-related enzymes in F. candida were not significantly affected when F. candida fed on the Bt rice materials, but were significantly increased when F. candida fed on the non-Bt rice materials containing E-64. The results demonstrate that Cry1C and Cry2A are not toxic to F. candida, and also indicate the absence of unintended effects on the collembolan caused by any change in plant tissue nutritional composition due to foreign gene transformation.

Recent studies showing the therapeutic effect of young blood on aging-associated deterioration of organs point to young blood as the solution for clinical problems related to old age. Given that defective autophagy has been implicated in aging and aging-associated organ injuries, this study was designed to determine the effect of young blood on aging-induced alterations in hepatic function and underlying mechanisms, with a focus on autophagy. Aged rats (22 months) were treated with pooled plasma (1 ml, intravenously) collected from young (3 months) or aged rats three times per week for 4 weeks, and 3-methyladenine or wortmannin was used to inhibit young blood-induced autophagy. Aging was associated with elevated levels of alanine transaminase and aspartate aminotransferase, lipofuscin accumulation, steatosis, fibrosis, and defective liver regeneration after partial hepatectomy, which were significantly attenuated by young plasma injections. Young plasma could also restore aging-impaired autophagy activity. Inhibition of the young plasma-restored autophagic activity abrogated the beneficial effect of young plasma against hepatic injury with aging. In vitro, young serum could protect old hepatocytes from senescence, and the antisenescence effect of young serum was abrogated by 3-methyladenine, wortmannin, or small interfering RNA to autophagy-related protein 7. Collectively, our data indicate that young plasma could ameliorate age-dependent alterations in hepatic function partially via the restoration of autophagy.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. In this study, we had analysed the copy number variations and heteroplasmic mutations of mitochondria (MT) in 88 HCC individuals. The average copy number of MT genome in normal samples was significantly greater than that in tumor samples. Overall, the number of heteroplasmic mutations in 88 tumor and their matched normal samples were 241 and 173, respectively. There was higher positive ratio of heteroplasmic mutations in tumor samples (86%) than normal samples (73%). Worthwhile mention, ND1 gene harbored greater mutation frequency and more nonsynonymous mutations in tumor samples. Interestingly, 202 tumor-specific heteroplasmic mutations were detected. Moreover, ND1, ND3, ND4, ND5 and ND6 genes had higher ratio of nonsynonymous versus synonymous mutations in tumor-specific heteroplasmic mutations. It might suggest that the disorder of NADH dehydrogenase (complex I) resulted by heteroplasmic mutations may have close relation with tumorigenesis of hepatocellular carcinoma. This study provided theoretical basis for further understanding mechanism of tumorigenesis from the perspective of mitochondrial heteroplasmic mutations.

Herpes simplex virus type 2 (HSV-2) infects human genital mucosa and establishes life-long latent infection. It is unmet need to establish a human cell-based microphysiological system for virus biology and anti-viral drug discovery. One of barriers is lacking of culture system of normal epithelial cells in vitro over decades. In this study, we established human normal vaginal epithelial cell (HNVEC) culture using co-culture system. HNVEC cells were then propagated rapidly and stably in a defined culture condition. HNVEC cells exhibited a normal diploid karyotype and formed the well-defined and polarized spheres in matrigel three-dimension (3D) culture, while malignant cells (HeLa) formed disorganized and nonpolar solid spheres. HNVEC cells had a normal cellular response to DNA damage and had no transforming property using soft agar assays. HNVEC expressed epithelial marker cytokeratin 14 (CK14) and p63, but not cytokeratin 18 (CK18). Next, we reconstructed HNVEC-derived 3D vaginal epithelium using air-liquid interface (ALI) culture. This 3D vaginal epithelium has the basal and apical layers with expression of epithelial markers as its originated human vaginal tissue. Finally, we established an HSV-2 infection model based on the reconstructed 3D vaginal epithelium. After inoculation of HSV-2 (G strain) at apical layer of the reconstructed 3D vaginal epithelium, we observed obvious pathological effects gradually spreading from the apical layer to basal layer with expression of a viral protein. Thus, we established an ex vivo 2D and 3D HSV-2 infection model that can be used for HSV-2 virology and anti-viral drug discovery.

The aim of the present study was to investigate the prevalence rate of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-positive individuals and to study the infection status of HCV RNA in HIV-infected individuals who did not have anti-HCV antibodies in the Guangxi province of China, in order to provide basis for screening and clinical treatment of hepatitis C in future. Data were collected from patients recruited via a questionnaire. Between August 2008 and January 2009, 300 HIV-infected individuals were randomly selected from various HIV monitoring points in Liuzhou and Qinzhou (Guangxi, China). In addition, 41 patients with only hepatitis C were recruited from a hospital clinic (First Affiliated Hospital of Guangxi Medical University, Nanning, China). HCV antibodies in patient serum samples were detected by ELISA. HCV RNA expression was detected using nested polymerase chain reaction (PCR), HCV RNA levels in the serum were evaluated using quantitative fluorescence PCR, and HCV genotypes were confirmed using restriction fragment length polymorphism. The infection rate of HCV in the HIV-infected people was 48.67%. The anti-HCV positive rate differed between routes of disease transmission: Anti-HCV positive rate was 63.7% among drug users, 34.96% among sex-transmitted persons and 1.37% among other persons. In the anti-HCV-negative group, the HCV RNA-positive rate was 26.62%. In the anti-HCV-positive group, HCV RNA positive rate was 78.08%. HCV RNA level of HIV/HCV coinfected patients was higher than those infected with HCV alone, and there was no difference of anti-HCV-positive rate among different levels of HCV RNA. HCV genotypes of HIV/HCV coinfected persons showed diversity across Guangxi, and the predominant ones were the 1b and mixed subtypes. The predominant HCV genotypes were 6a, mixed subtypes and 3b amongst patients that contracted HCV via drug use-related routes of transmission. The patients with HCV transmission routes other than drug-related routes possessed 1b and 1a+1b genotypes. In conclusion, there was a large proportion of HIV infected persons with mixed HCV infection in the Guangxi province of China. The present results show that 26.62% of HCV-infected persons will be fail to be diagnosed with hepatitis C virus coinfection if we simply use ELISA to detect HCV antibody. The predominant HCV genotypes were 1b, mixed, 6a and 3b in HIV/HCV coinfected persons.

Metastasis represents a key factor associated with poor prognosis of head and neck squamous cell carcinoma (HNSC). However, the underlying molecular mechanisms remain largely unknown. In this study, our liquid chromatography with tandem mass spectrometry analysis revealed a number of significantly differentially expressed membrane/membrane-associated proteins between high invasive UM1 and low invasive UM2 cells. One of the identified membrane proteins, Syntenin-1, was remarkably up-regulated in HNSC tissues and cell lines when compared to the controls, and also over-expressed in recurrent HNSC and high invasive UM1 cells. Syntenin-1 over-expression was found to be significantly associated with lymph node metastasis and disease recurrence. HNSC patients with higher syntenin-1 expression had significantly poorer long term overall survival and similar results were found in many other types of cancers based on analysis of The Cancer Genome Atlas data. Finally, knockdown of syntenin-1 inhibited the proliferation, migration and invasion of HNSC cells, and opposite findings were observed when syntenin-1 was over-expressed. Collectively, our studies indicate that syntenin-1 promotes invasion and progression of HNSC. It may serve as a valuable biomarker for lymph node metastasis or a potential target for therapeutic intervention in HNSC.

Bt rice can control yield losses caused by lepidopteran pests but may also harm nontarget species and reduce important ecosystem services. A comprehensive data set on herbivores, natural enemies, and their interactions in Chinese rice fields was compiled. This together with an analysis of the Cry protein content in arthropods collected from Bt rice in China indicated which nontarget species are most exposed to the insecticidal protein and should be the focus of regulatory risk assessment.

FK866 exhibits a protective effect on D-galactosamine (GaIN)/lipopolysaccharide (LPS) and concanavalin A (ConA)-induced acute liver failure (ALF), but the mechanism by which FK866 affords this benefit has not yet been elucidated. Autophagy has a protective effect on acute liver injury. However, the contribution of autophagy to FK866-conferred hepatoprotection is still unclear. This study aimed to investigate whether FK866 could attenuate GaIN/LPS and ConA-induced ALF through c-jun-N-terminal kinase (JNK)-dependent autophagy. In vivo, Mice were pretreated with FK866 at 24, 12, and 0.5 h before treatment with GaIN/LPS and ConA. 3-methyladenine (3MA) or rapamycin were used to determine the role of autophagy in FK866-conferred hepatoprotection. In primary hepatocytes, autophagy was inhibited by 3MA or autophagy-related protein 7 (Atg7) small interfering RNA (siRNA). JNK was suppressed by SP600125 or Jnk siRNA. FK866 alleviated hepatotoxicity and increased autophagy while decreased JNK activation. Suppression of autophagy abolished the FK866-conferred protection. Inhibition of JNK increased autophagy and exhibited strongly protective effect. Collectively, FK866 could ameliorate GaIN/LPS and ConA-induced ALF through induction of autophagy while suppression of JNK. These findings suggest that FK866 acts as a simple and applicable preconditioning intervention to protect against ALF; autophagy and JNK may also provide therapeutic targets for ALF treatment.

Type 2 diabetes (T2D) is a high-risk factor for Alzheimer's disease (AD) due to impaired insulin signaling pathway in brain. Capsaicin is a specific transient receptor potential vanilloid 1 (TRPV1) agonist which was proved to ameliorate insulin resistance. In this study, we investigated whether dietary capsaicin could reduce the risk of AD in T2D. T2D rats were fed with capsaicin-containing high fat (HF) diet for 10 consecutive days (T2D+CAP). Pair-fed T2D rats (T2D+PF) fed with the HF-diet of average dose of T2D+CAP group were included to control for the effects of reduced food intake and body weight. Capsaicin-containing standard chow was also introduced to non-diabetic rats (NC+CAP). Blood glucose and insulin were monitored. The phosphorylation level of tau at individual sites, the activities of phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) and glycogen synthase kinase-3β (GSK-3β) were analyzed by Western blots. The results revealed that the levels of phosphorylated tau protein at sites Ser199, Ser202 and Ser396 in hippocampus of T2D+CAP group were decreased significantly, but these phospho-sites in T2D+PF group didn't show such improvements compared with T2D group. There were almost no changes in non-diabetic rats on capsaicin diet (NC+CAP) compared with the non-diabetic rats with normal chow (NC). Increased activity of PI3K/AKT and decreased activity of GSK-3β were detected in hippocampus of T2D+CAP group compared with T2D group, and these changes did not show in T2D+PF group either. These results demonstrated that dietary capsaicin appears to prevent the hyperphosphorylation of AD-associated tau protein by increasing the activity of PI3K/AKT and inhibiting GSK-3β in hippocampus of T2D rats, which supported that dietary capsaicin might have a potential use for the prevention of AD in T2D.

There is limited literature investigating the effects of body mass index (BMI) and androgen level on in vitro fertilization (IVF) outcomes with a gonadotropin-releasing hormone (GnRH)-antagonist protocol in polycystic ovary syndrome (PCOS). Androgen-related variation in the effect of body mass index (BMI) on IVF outcomes remains unknown.

Previous studies have indicated that osteogenic protein-1 has protective effects on the biological functions of intervertebral disc cells. Hyperosmolarity is an important physicochemical factor within the disc nucleus pulposus (NP) region, which obviously promotes NP cell apoptosis.

Vitamin A (retinol) is important for multiple functions in mammals. In testis, the role of vitamin A in the regulation of testicular functions is clearly involved in rodents. It is essential for sperm production. Vitamin A deficiency adversely affects testosterone secretion. Adult Leydig cells are responsible for testosterone production in male. The role of vitamin A in regulating the differentiation of Leydig cells is still unknown. In this study, we explored the roles and underlying mechanisms of vitamin A in Leydig cell differentiation. We found that vitamin A could regulate the Leydig cells differentiation. Leydig cell differentiation is adversely affected in mice maintained on a vitamin A-free diet. This effect is mediated by alcohol dehydrogenase 1 (ADH1). ADH1 could increase retinoic acid (RA) synthesis, then RA facilitates Leydig cell differentiation by activating the steroidogenic factor 1 gene (Nr5a1) promoter activity, which consequently promotes Leydig cell specific gene expression, resulting in progenitor Leydig cells differentiation into functional Leydig cells. This is the first study connecting a metabolic enzyme of retinol (ADH1) to the the regulation of Leydig cell differentiation, which will provide experimental evidence for the development of therapeutics to promote Leydig regeneration through the administration of a RA signaling regulator or a vitamin A supplement.

This research is aimed to study the resistance and molecular epidemiological characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP).

Background: Clear cell renal cell carcinoma (ccRCC) is characterized by high metastatic potential, and the epithelial-mesenchymal transition (EMT) has been shown to play a key role in multiple cancer progression, migration and metastasis and is the leading cause of poor prognosis. Currently, tumor necrosis factor-α-induced protein 8 (TNFAIP8/TIPE) is a newly discovered tumorigenesis factor, and TNFAIP8 and the EMT influence the migration of renal cancer cells. Methods: In this study, we first analyzed the relationship between TNFAIP8 and ccRCC using bioinformatics, followed by immunohistochemistry to evaluate the relationship between the two in clinical samples. Subsequently, reverse transcription PCR and western blotting confirmed the expression of TNFAIP8 in ccRCC cells. Furthermore, we measured the migration and invasion abilities by using wound healing and transwell assays after overexpression or knockdown of TNFAIP8 in cells. In addition, we verified whether TNFAIP8 affects the EMT process in ccRCC by quantitative real-time PCR, western blotting, immunohistochemistry and immunofluorescence experiments. Results: Through database analysis, we found that TNFAIP8 was highly expressed in ccRCC patients and was positively correlated with tumor stage and grade, indicating that TNFAIP8 is associated with the development of advanced ccRCC and poor prognosis. We subsequently confirmed that TNFAIP8 was abnormally overexpressed in clinical samples and ccRCC cell lines and that TNFAIP8 promoted ccRCC cell migration and invasion in vitro. Finally, we found that TNFAIP8 regulated EMT-related molecule expression and regulated the EMT process. Conclusion: High expression of TNFAIP8 reinforces migration and regulates the EMT in ccRCC, conferring the metastatic potential of ccRCC and suggesting that TNFAIP8 may be a potential therapeutic target for the treatment of advanced ccRCC.

The expression of C-terminal phosphorylated Smad3 (pSmad3C) is down-regulated with the progression of liver disease. Thus, we hypothesized that pSmad3C expression may be negatively related to liver disease. To develop novel therapeutic strategies, a suitable animal model is required that will allow researchers to study the effect of Smad3 domain-specific phosphorylation on liver disease progression. The current study aimed to construct a new mouse model with the Smad3 C-terminal phosphorylation site mutation and to explore the effects of this mutation on CCl4 -induced inflammation. Smad3 C-terminal phosphorylation site mutant mice were generated using TetraOne™ gene fixed-point knock-in technology and embryonic stem cell microinjection. Resulting mice were identified by genotyping, and the effects on inflammation were explored in the presence or absence of CCl4 . No homozygous mice were born, indicating that the mutation is embryonic lethal. There was no significant difference in liver phenotype and growth between the wild-type (WT) and heterozygous (HT) mice in the absence of reagent stimulation. After CCl4 -induced acute and chronic liver damage, liver pathology, serum transaminase (ALT/AST) expression and levels of inflammatory factors (IL-6/TNF-α) were more severely altered in HT mice than in WT mice. Furthermore, pSmad3C protein levels were lower in liver tissue from HT mice. These results suggest that Smad3 C-terminal phosphorylation may have a protective effect during the early stages of liver injury. In summary, we have generated a new animal model that will be a novel tool for future research on the effects of Smad3 domain-specific phosphorylation on liver disease progression.

MiR-133a has been confirmed to be involved in the development of multiple cancers including non-small cell lung cancer (NSCLC). However, the precise molecular mechanism has not yet been fully elucidated. The purpose of this study was to investigate the functional role and underlying mechanism of miR-133a in the progression of NSCLC.

Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk. Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear.