Acetyl-CoA carboxylase 1 depletion suppresses de novo fatty acid synthesis and mitochondrial ß-oxidation in castration-resistant prostate cancer cells.

Cancer cells, including those of prostate cancer (PCa), often hijack intrinsic cell signaling to reprogram their metabolism. Part of this reprogramming includes the activation of de novo synthesis of fatty acids that not only serve as building blocks for membrane synthesis but also as energy sources for cell proliferation. However, how de novo fatty acid synthesis contributes to PCa progression is still poorly understood. Herein, by mining public datasets, we discovered that the expression of acetyl-CoA carboxylase alpha (ACACA), which encodes acetyl-CoA carboxylase 1 (ACC1), was highly expressed in human PCa. In addition, patients with high ACACA expression had a short disease-free survival time. We also reported that depletion of ACACA reduced de novo fatty acid synthesis and PI3K/AKT signaling in the human castration-resistant PCa (CRPC) cell lines DU145 and PC3. Furthermore, depletion of ACACA downregulates mitochondrial beta-oxidation, resulting in mitochondrial dysfunction, a reduction in ATP production, an imbalanced NADP+/NADPhydrogen(H) ratio, increased reactive oxygen species, and therefore apoptosis. Reduced exogenous fatty acids by depleting lipid or lowering serum supplementation exacerbated both shRNA depletion and pharmacological inhibition of ACACA-induced apoptosis in vitro. Collectively, our results suggest that inhibition of ectopic ACACA, together with suppression of exogenous fatty acid uptake, can be a novel strategy for treating currently incurable CRPC.

IRE1 signaling regulates chondrocyte apoptosis and death fate in the osteoarthritis.

IRE1 is an important central regulator of unfolded protein response (UPR) in the endoplasmic reticulum (ER) because of its ability to regulate cell fate as a function of stress sensing. When misfolded proteins accumulated in chondrocytes ER, IRE1 disintegrates with BIP/GRP78 and undergoes dimer/oligomerization and transautophosphorylation. These two processes are mediated through an enzyme activity of IRE1 to activate endoribonuclease and generates XBP1 by unconventional splicing of XBP1 messenger RNA. Thereby promoting the transcription of UPR target genes and apoptosis. The deficiency of inositol-requiring enzyme 1α (IRE1α) in chondrocytes downregulates prosurvival factors XBP1S and Bcl-2, which enhances the apoptosis of chondrocytes through increasing proapoptotic factors caspase-3, p-JNK, and CHOP. Meanwhile, the activation of IRE1α increases chondrocyte viability and reduces cell apoptosis. However, the understanding of IRE1 responses and cell death fate remains controversial. This review provides updated data about the role IRE1 plays in chondrocytes and new insights about the potential efficacy of IRE1 regulation in cartilage repair and osteoarthritis treatment.

Metabolic Differences between Unilateral and Bilateral Renal Stones and Their Association with Markers of Kidney Injury.

PURPOSE: Urinary stone disease (USD) has been associated with an increased risk of chronic kidney disease (CKD) and end-stage renal disease in Western populations. However, the metabolic disorders associated with unilateral and bilateral renal stones and the association of these types of stones with CKD and kidney tubular injury markers, such as urine N-acetyl-ß-D-glucosaminidase (NAG) and alpha-1-microglobulin (α1-MG), have not been fully examined. MATERIALS AND METHODS: We performed a cross-sectional study of 10,281 participants in rural China in 2014. All the subjects underwent renal ultrasound to detect USD; stone formers were divided into groups with unilateral or bilateral renal stones by ultrasound examinations. CKD was defined as a decreased estimated glomerular filtration rate (eGFR, <60 mL/minute/1.73 m2) and/or albuminuria (albumin-to-creatinine ratio ≥30 mg/gm). Increased urine NAG and α1-MG levels were defined as their values above the 75th percentile of the sample distribution. RESULTS: Among all the participants, 4.9% (507) had unilateral renal stones, and 0.7% (75) had bilateral renal stones. The proportion of CKD in the nonstone, unilateral and bilateral renal stone formers was 11.0%, 19.2% and 29.7%, respectively (p for trend <0.001). Individuals with bilateral renal stones had the highest proportion of metabolic components, such as elevated blood pressure and serum glucose. In multivariate analyses after adjustment for multiple confounders, bilateral renal stones were significantly associated with an increased risk of decreased eGFR (OR 3.38; 95% CI 1.05-10.90), albuminuria (OR 3.01; 95% CI 1.76-5.13), CKD (OR 3.18; 95% CI 1.88-5.36), increased urine NAG-to-creatinine ratio (OR 1.95; 95% CI 1.21-3.16) and α1-MG-to-creatinine ratio levels (OR 2.54; 95% CI 1.56-4.12) compared with the lack of stones. CONCLUSIONS: Bilateral renal stones were associated with a higher risk of CKD and higher levels of kidney tubular injury markers. Clinicians should pay attention to metabolic disorders in bilateral renal stone formers.

Application of Duplex Droplet Digital PCR Detection of miR-888 and miR-891a in Semen Identification.

OBJECTIVES: To establish a system for simultaneous detection of miR-888 and miR-891a by droplet digital PCR (ddPCR), and to evaluate its application value in semen identification. METHODS: The hydrolysis probes with different fluorescence modified reporter groups were designed to realize the detection of miR-888 and miR-891a by duplex ddPCR. A total of 75 samples of 5 body fluids (including peripheral blood, menstrual blood, semen, saliva and vaginal secretion) were detected. The difference analysis was conducted by Mann-Whitney U test. The semen differentiation ability of miR-888 and miR-891a was evaluated by ROC curve analysis and the optimal cut-off value was obtained. RESULTS: There was no significant difference between the dual-plex assay and the single assay in this system. The detection sensitivity was up to 0.1 ng total RNA, and the intra- and inter-batch coefficients of variation were less than 15%. The expression levels of miR-888 and miR-891a detected by duplex ddPCR in semen were both higher than those in other body fluids. ROC curve analysis showed that the AUC of miR-888 was 0.976, the optimal cut-off value was 2.250 copies/µL, and the discrimination accuracy was 97.33%; the AUC of miR-891a was 1.000, the optimal cut-off value was 1.100 copies/µL, and the discrimination accuracy was 100%. CONCLUSIONS: In this study, a method for detection of miR-888 and miR-891a by duplex ddPCR was successfully established. The system has good stability and repeatability and can be used for semen identification. Both miR-888 and miR-891a have high ability to identify semen, and the discrimination accuracy of miR-891a is higher.

LPS induced PCT production via TLR-4/NF-кB passway:it is the difference of G-/G+ bacteremia rats.

Sepsis by Gram-negative bacteria infection leads to further increase in procalcitonin (PCT). Herein, we examined the expression of PCT after 24 h in rats by injecting Escherichia coli (E. coli) or Staphylococcus aureus (SA). Healthy male SD rats were divided into six groups (n = 8): (1) Control group: no treatment; (2) SA group: injected with 106CFU/ml SA suspension 0.1 ml in the tail vein; (3) SA and antibiotics group: injected with 106/ml SA bacterial suspension 0.1 ml and 4 mg/kg Cefotaxime sodium, q8h in the tail vein; (4) E. coli group: injected with 106CFU/ml E. coli suspension 0.1 ml in the tail vein; (5) E. coli and antibiotics group: injected with 106/ml E. coli bacterial suspension 0.1 ml and 4 mg/kg Cefotaxime sodium, q8h in the tail vein; and (6) Endotoxin group: injected with 5 mg/kg endotoxin in the tail vein. Expression of PCT was significantly increased in the E. coli, SA or endotoxin-induced bacteremia rats than in the control rats. Compared with SA, PCT was more significantly increased in E. coli rats. NF-κB changes were in line with PCT. Next, we investigated whether the expression of PCT decreased when TLR4 or NF-κB were inhibited after injecting E. coli in rats. A total of 40 healthy male SD rats were divided into five groups (n = 8): (1) Control group: no treatment; (2) E. coli group: injected with 106CFU/ml E. coli suspension 0.1 ml in the tail vein. (3) E. coli and PBS group: injected with 106CFU/ml E. coli suspension 0.1 ml and PBS 0.1 ml in the tail vein. (4) E. coli and TAK242: injected with 106CFU/ml E. coli suspension 0.1 ml and 3 mg/kg TAK242 in the tail vein. (5) E. coli and BAY-11-7082: injected with 106/ml E. coli suspension 0.1 ml and 25 mg/kg BAY-11-7082 in the tail vein. A marked increase of TLR4, NF-κB, LPS and PCT expression was observed in the lungs after E. coli induced bacteremia. Expressions of TLR4, NF-κB, and PCT proteins were decreased in the lungs at 24 h after injection of TAK-242 or BAY-11-7082. In summary, this study suggested that LPS is the key factor for differential expression of PCT between E. coli and SA bacteremia. E. coli induces PCT elevation via the TLR4/NF-κB pathway.

Protective effect of Phaeoporus obliquus polysaccharide against acute liver injury induced by carbon tetrachloride and alcohol in mice.

Studied the optimum extraction process of polysaccharide from Phaeoporus obliquus and the effect of Phaeoporus obliquus polysaccharide on carbon tetrachloride (CCl4)- or alcohol-induced acute liver injury in mice. The main factor in influencing the extraction rate of Phaeoporus obliquus polysaccharide were extraction power and time, which was a kind of pyran glucose by infrared spectroscopy. CCl4 and alcohol were employed respectively to establish CCl4 and alcohol-induced acute liver injury mouse models. Compared with model groups mice, Phaeoporus obliquus polysaccharide treatment at the doses of 100mg/kg and 200mg/kg exhibited an obvious reduction liver index, ALP, ALT, AST levels, MDA content and TNF-α level (p<0.01) and SOD activity was increased, which was in a dose-dependent manner. Compared with the model group, the necrosis degree of hepatocytes was obviously reduced and the small fat droplets were formed in some cytoplasm, especially in high dose group, which the liver cells recovered to the level of normal group. Rt-PCR results showed that the expression of CYP2E1 mRNA in liver tissues of Phaeoporus obliquus polysaccharide groups were significantly reduced, and the difference were statistically significant compared with the model group (p<0.05). These results demonstrated that Phaeoporus obliquus polysaccharide has significantly hepatoprotective effect on CCl4 and alcohol-induced acute liver injury in mice.

miR-885-5p inhibits proliferation and metastasis by targeting IGF2BP1 and GALNT3 in human intrahepatic cholangiocarcinoma.

The incidence of intrahepatic cholangiocarcinoma (iCCA) continues to increase worldwide, however its molecular pathogenesis remains poorly understood. Recent studies have implicated microRNAs in iCCA progression. In this study, we demonstrated that miR-885-5p was significantly decreased in iCCA tissues. Downregulation of miR-885-5p was correlated with vascular invasion, lymph node metastasis, unfavorable overall survival, and shorter disease-free survival. Silencing or overexpressing miR-885-5p by lentiviral approaches significantly influenced iCCA cell proliferation and metastasis in vitro and in vivo. Mechanistically, overexpression of miR-885-5p inhibited iCCA metastasis and proliferation by directly inhibiting GALNT3 as well as by indirectly promoting the downregulation of insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1). Furthermore, miR-885-5p inhibited iCCA metastasis by downregulating the PI3K/AKT/MMPs signaling pathway via targeting GALNT3. Collectively, we demonstrated that miR-885-5p was an important mediator of iCCA proliferation and metastasis by regulating GALNT3 and IGF2BP1, thus offering a potential target for iCCA treatment.

Laparoscopic nephrectomy for giant benign renal schwannoma: a case report and review of literature.

Benign giant renal schwannoma is rarely found and the diagnosis difficulty only depends on physical and imagological examination. Pathological examination is essential to confirm the diagnosis of renal schwannoma. Nephrectomy and tumorectomy are primary treatments for renal schwannoma. Although most of the reported patients present satisfactory outcome, however, there is still not sufficient evidence to reveal the biological characteristics and post-operation recurrence rate of renal schwannoma. Herein, we report a rare case of giant and complicated renal schwannoma. A 56-years-old female patient was admitted to the urology department due to left lower back pain for approximately 5 days. No positive signs and other special abnormalities were found. CT scan presented a soft tissue tumor with inhomogeneous enhanced in the renal hilum. Surgery was performed to excise the tumor and left renal. Renal schwannoma was confirmed by pathological examination. At the 6-month follow-up, no evidence of recurrence was found. Our present report could provide more material for further study.

Cooperative activation of PI3K by Ras and Rho family small GTPases.

Phosphoinositide 3-kinases (PI3Ks) and Ras and Rho family small GTPases are key regulators of cell polarization, motility, and chemotaxis. They influence each other's activities by direct and indirect feedback processes that are only partially understood. Here, we show that 21 small GTPase homologs activate PI3K. Using a microscopy-based binding assay, we show that K-Ras, H-Ras, and five homologous Ras family small GTPases function upstream of PI3K by directly binding the PI3K catalytic subunit, p110. In contrast, several Rho family small GTPases activated PI3K by an indirect cooperative positive feedback that required a combination of Rac, CDC42, and RhoG small GTPase activities. Thus, a distributed network of Ras and Rho family small GTPases induces and reinforces PI3K activity, explaining past challenges to elucidate the specific relevance of different small GTPases in regulating PI3K and controlling cell polarization and chemotaxis.

Different types of low back pain in relation to pre- and post-natal maternal depressive symptoms.

BACKGROUND: Low back pain (LBP) is a common musculoskeletal problem during pregnancy, with an estimated prevalence ranging from 30-78% (Mota MJ et al. J Back Musculoskelet Rehabil 28(2):351-7,2015 and Abebe E et al. J Med Sc Tech 3(3). 37-44,2014). Women reporting LBP are at increased risk of developing perinatal depression. Pregnancy-related LBP is highly heterogeneous and can be divided into lumbar pain (LP), posterior pelvic pain (PPP), and combined pain (CP). Therefore, the purpose of this study was to investigate the associations between LBP and perinatal depressive symptoms. METHODS: This was a retrospective case-control study conducted from January 2016 to April 2019. A total of 484 pregnant women were enrolled in this study: a case group of 242 pregnant women who were diagnosed with LBP and an age-matched control group of 242 pregnant women without LBP. The Edinburgh Postnatal Depression Scale (EPDS), LBP characteristics, and questionnaires about pregnancy that included demographic, parity, work, comorbidity, and previous pregnancy data were completed and compared between the case group and the control group. RESULTS: A total of 68 of 242 (28.1%) women experienced PPP, 142 (58.7%) had lumbar pain(LP), and 32 (13.2%) had combined pain. Furthermore, 26.5% of women with prenatal depression in the LP subgroup remained depressed 6 months postnatally, while the percentages for women in the PPP subgroup and CP subgroup were just 10.6% and 15.6%, respectively. The percentage of women who recovered anytime between delivery and six months postnatally in the PPP subgroup was significantly higher than that in the LP subgroup (31.7% vs. 14.7%, P < 0.001). CONCLUSIONS: There is a difference in the prevalence of prenatal, postnatal, and perinatal depressive symptoms among pregnant women with different types of LBP. It is necessary to screen prenatal and postnatal depression separately and differentiate the types of LBP during pregnancy. Attention to these factors may help to outline better management strategies to improve maternal health.

[Genome-wide analysis of LBD(lateral organ boundaries domain) gene family in Cannabis sativa of traditional Chinese medicine hemp seed].

LBD(lateral organ boundaries)transcription factors play an important role in the regulation of plant growth, development and secondary metabolism. In order to explore the function of LBD genes in cannabis, the Cannabis sativa genome and transcriptome were used to identify the C. sativa LBD gene family, and analyzed their expression patterns. Our results showed that the cannabis LBD contains 32 members, which were divided into two major categories, seven sub-families. Class Ⅰ was divided into 5 sub-families, named Class Ⅰ_a to Class Ⅰ_e, while Class Ⅱ was divided into 2 sub-families, including Class Ⅱ_a and Class Ⅱ_b. Analysis showed that the number of amino acids encoded LBDs was between 172 and 356, and the isoelectric point was between 4.92 and 9.43. The mole-cular weight of LBD was between 18 862.92 Da and 40 081.33 Da, and most members are located in the nucleus. Chromosome positioning of LBD showed that 32 members were unevenly distributed on 10 chromosomes of C. sativa LBD transcription factor domain, gene structure and motifs are relatively conservative, and the characteristics of different class members are similar. The upstream promoter region of the gene contains a variety of cis-acting elements related to plant hormones and environmental factors, C. sativa LBD genes have different expression patterns in the stems, leaves, and flowers of ZYS varieties(low tetrahydrocannabinol, high cannabidiol). The members of the LBD gene family are mainly expressed in the flowers and stems of ZYS varieties, while members expressed in the leaves very few; Class Ⅱ members CsLBD21 and CsLBD23 are expressed in flowers and stems, and CsLBD8 and CsLBD18 are expressed in flowers, stems and leaves. These genes may participate in the growth and development of cannabis and affect the biosynthesis of cannabinoids. This study laid the foundation for the subsequently functional research of the cannabis LBD gene family.

[Molecular regulatory mechanisms of hypoxia-inducible factor and interventional effect of Chinese herbal medicine].

Hypoxia-inducible factors(HIFs)are the key transcription factors that sense and regulate cellular oxygen concentration in vivo. HIF-1 is composed of 2 subunits,α and ß,in which,the molecular regulatory mechanism of HIF-1α involves the main processes of its degradation and activation. The degradation of HIF-1α is regulated by oxygen-dependent pathways,including "von hippel-lindau protein(pVHL)-dependent pathway" and "pVHL-independent pathway". The activation of HIF-1α is regulated by oxygen-independent pathways,including mammalian target of rapamycin(mTOR)/eukaryotic initiation factor 4 E-binding protein 1(4 EBP1)/HIF-1α pathway,phosphatidylinositol 3-kinase(PI3 K)/proteirrserinc-threonine kinases(Akt)/HIF-1α pathway and silent information regulator1(Sirt1)/HIF-1α pathway. In recent years,based on the molecular regulatory mechanism of HIFs,Roxadustat,a new drug for the treatment of renal anemia has been developed. Besides, some macromolecular substances with similar pharmacological effect to HIFs have been found in the extracts from Chinese herbal medicine(CHM),such as emodin,notoginseng triterpenes,honokiol and clematichinenoside. These natural macromolecular substances play the regulatory roles in inflammatory response,epigenetic modification and auto-phagy. It is worth noting that,for common hypoxic-related diseases including diabetic kidney disease,HIFs-mediated "pyroptosis" may be a new target of CHMs for clearing dampness and heat and its representative classical prescriptions(Ermiao Pills)in treating inflammatory injury in cells and tissues.

[Study on chemical bibenzyls in Dendrobium gratiosissimum].

Nineteen compounds were isolated and structurally characterized from an ethanol extract of Dendrobium gratiossimum, including dendrogratiol A(1), DDB-1(2), 3,4-dihydroxyl-5,3',4'-trimethoxybibenzyl(3), amoenylin(4), chrysotoxine(5), DTB(6), 3,4,4'-trihydroxyl-5,3'-dimethoxybenzyl(7), 3-methylgiga(8), aloifol(9), gigantol tetramethyl ether(10), batatasin Ⅲ(11), moscatilin(12), moniliformine(13), gigantol(14), DMB(15), flavanthrinin(16), cannithrene-2(17), 3,4-dihydroxyl-5,4'-dimethoxystilbene(18) and 4-hydroxy-3,5,4'-trimethoxystilbene(19). 1 was a new compound, and 2-10, 16, 18 and 19 were obtained from this plant species for the first time. In vitro cytotoxic and antiviral activities of these isolates were evaluated, which displayed that 4 showed moderate cytotoxicity against human hepatoma cell line HepG2 with the IC_(50) of 10.15 µmol·L~(-1); 7 and 12 exhibited moderate inhibitory activity towards HIV virus with the IC_(50) of 9.35 and 9.15 µmol·L~(-1), respectively; and 10 displayed inhibitory activity against IAV virus with the IC_(50) of 8.90 µmol·L~(-1).

Salmonella exploits host Rho GTPase signalling pathways through the phosphatase activity of SopB.

Salmonella uses Type 3 secretion systems (T3SSs) to deliver virulence factors, called effectors, into host cells during infection. The T3SS effectors promote invasion into host cells and the generation of a replicative niche. SopB is a T3SS effector that plays an important role in Salmonella pathogenesis through its lipid phosphatase activity. Here, we show that SopB mediates the recruitment of Rho GTPases (RhoB, RhoD, RhoH, and RhoJ) to bacterial invasion sites. RhoJ contributes to Salmonella invasion, and RhoB and RhoH play an important role in Akt activation. R-Ras1 also contributes to SopB-dependent Akt activation by promoting the localised production of PI(3,4)P2 /PI(3,4,5)P3 . Our studies reveal new signalling factors involved in SopB-dependent Salmonella infection.

PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front.

Cells migrate by directing Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42) activities and by polymerizing actin toward the leading edge of the cell. Previous studies have proposed that this polarization process requires a local positive feedback in the leading edge involving Rac small GTPase and actin polymerization with PI3K likely playing a coordinating role. Here, we show that the pleckstrin homology and RhoGEF domain containing G3 (PLEKHG3) is a PI3K-regulated Rho guanine nucleotide exchange factor (RhoGEF) for Rac1 and Cdc42 that selectively binds to newly polymerized actin at the leading edge of migrating fibroblasts. Optogenetic inactivation of PLEKHG3 showed that PLEKHG3 is indispensable both for inducing and for maintaining cell polarity. By selectively binding to newly polymerized actin, PLEKHG3 promotes local Rac1/Cdc42 activation to induce more local actin polymerization, which in turn promotes the recruitment of more PLEKHG3 to induce and maintain cell front. Thus, autocatalytic reinforcement of PLEKHG3 localization to the leading edge of the cell provides a molecular basis for the proposed positive feedback loop that is required for cell polarization and directed migration.

Synthetic Lateral Metal-Semiconductor Heterostructures of Transition Metal Disulfides.

Lateral heterostructures with planar integrity form the basis of two-dimensional (2D) electronics and optoelectronics. Here we report that, through a two-step chemical vapor deposition (CVD) process, high-quality lateral heterostructures can be constructed between metallic and semiconducting transition metal disulfide (TMD) layers. Instead of edge epitaxy, polycrystalline monolayer MoS2 in such junctions was revealed to nucleate from the vertices of multilayered VS2 crystals, creating one-dimensional junctions with ultralow contact resistance (0.5 kΩ·µm). This lateral contact contributes to 6-fold improved field-effect mobility for monolayer MoS2, compared to the conventional on-top nickel contacts. The all-CVD strategy presented here hence opens up a new avenue for all-2D-based synthetic electronics.

Efficient and tumor-specific knockdown of MTDH gene attenuates paclitaxel resistance of breast cancer cells both in vivo and in vitro.

BACKGROUND: Drug resistance of paclitaxel (TAX), the first-line chemotherapy drug for breast cancer, was reported to develop in 90% of patients with breast cancer, especially metastatic breast cancer. Investigating the mechanism of TAX resistance of breast cancer cells and developing the strategy improving its therapeutic efficiency are crucial to breast cancer cure. METHODS AND RESULTS: We here report an elegant nanoparticle (NP)-based technique that realizes efficient breast cancer treatment of TAX. Using lentiviral vector-mediated gene knockdown, we first demonstrated that TAX therapeutic efficiency was closely correlated with metadherin (MTDH) gene expression in breast cancer cell lines. This finding was also supported by efficacy of TAX treatment in breast cancer patients from our clinical studies. Specifically, TAX treatment became more effective when MTDH expression was decreased in MCF-7 cancer cells by the blocking nuclear factor-kappa B (NF-κB) pathway. Based on these findings, we subsequently synthesized a polymeric NP that could co-deliver MTDH-small interfering RNA (MTDH-siRNA) and TAX into the breast cancer tumors in tumor-bearing mice. The NPs were composed of a cationic copolymer, which wrapped TAX in the inside and adsorbed the negatively charged siRNA on their surface with high drug-loading efficiency and good stability. CONCLUSIONS: NP-based co-delivery approach can effectively knock down the MTDH gene both in vitro and in vivo, which dramatically inhibits breast tumor growth, achieving effective TAX chemotherapy treatment without overt side effects. This study provides a potential therapeutic strategy for the treatment of a wide range of solid tumors highly expressing MTDH.

Compared cardiorespiratory endurance and musculoskeletal legs explosive power in students of Tsinghua University Beijing China and University of Sindh Pakistan.

OBJECTIVE: To assess the health-related physical fitness status of students and the attributes of performance in terms of endurance and power. METHODS: The cross-sectional study was conducted at University of Sindh, Jamshoro, Pakistan, and Tsinghua University, Beijing, China, during academic session of January 2012 to December 2013, and comprised an equal number of male and female students aged 18-23 years. Prior to the assessment, physical activity readiness questionnaire was filled by all the subjects, while standardised health-related physical fitness criterion was used to make comparisons in terms of oxygen consumption. . RESULTS: There were 600 subjects in all; 300(50%) at each of the two centres, and at both centres, there were 150(25%) boys and 150(25%) girls. Both for power and endurance, mean values of Chinese students were significantly better than their Pakistani counterparts (p<0.05). CONCLUSIONS: Chinese students had better health-related physical fitness levels than Pakistani students of either gender.

Release of Infectious Hepatitis C Virus from Huh7 Cells Occurs via a trans-Golgi Network-to-Endosome Pathway Independent of Very-Low-Density Lipoprotein Secretion.

UNLABELLED: The release of infectious hepatitis C virus (HCV) particles from infected cells remains poorly characterized. We previously demonstrated that virus release is dependent on the endosomal sorting complex required for transport (ESCRT). Here, we show a critical role of trans-Golgi network (TGN)-endosome trafficking during the assembly, but principally the secretion, of infectious virus. This was demonstrated by both small interfering RNA (siRNA)-mediated silencing of TGN-associated adaptor proteins and a panel of dominant negative (DN) Rab GTPases involved in TGN-endosome trafficking steps. Importantly, interfering with factors critical for HCV release did not have a concomitant effect on secretion of triglycerides, ApoB, or ApoE, indicating that particles are likely released from Huh7 cells via pathways distinct from that of very-low-density lipoprotein (VLDL). Finally, we show that HCV NS2 perturbs TGN architecture, redistributing TGN membranes to closely associate with HCV core protein residing on lipid droplets. These findings support the notion that HCV hijacks TGN-endosome trafficking to facilitate particle assembly and release. Moreover, although essential for assembly and infectivity, the trafficking of mature virions is seemingly independent of host lipoproteins. IMPORTANCE: The mechanisms by which infectious hepatitis C virus particles are assembled and released from the cell are poorly understood. We show that the virus subverts host cell trafficking pathways to effect the release of virus particles and disrupts the structure of the Golgi apparatus, a key cellular organelle involved in secretion. In addition, we demonstrate that the mechanisms used by the virus to exit the cell are distinct from those used by the cell to release lipoproteins, suggesting that the virus effects a unique modification to cellular trafficking pathways.