Treatment outcome of new pulmonary tuberculosis in Guangzhou, China 1993–2002: a register-based cohort study

<p>Abstract</p> <p>Background</p> <p>Completion of treatment for tuberculosis (TB) is of utmost priority for TB control programs. The aims of this study were to evaluate the treatment outcome of TB cases registered in Guangzhou during the period 1993–2002, and to identify factors associated with treatment success.</p> <p>Methods</p> <p>Two (of eight) districts in Guangzhou were selected randomly as objects of study and their surveillance database was analyzed to assess the treatment outcome and identify factors associated with treatment success for TB cases registered in Guangzhou. Six treatment outcome criteria were assessed based on guidelines set by the World Health Organization (WHO). Logistic regression was used to estimate risk factors for treatment outcome.</p> <p>Results</p> <p>A total of 6743 pulmonary tuberculosis cases (4903 males, 1840 females) were included in this study. The treatment success rate (including cured and complete treatment) was 88% (95%CI 87%–89%). One hundred and eight-six (2.8%) patients died and 401 (5.9%) patients defaulted treatment. In multivariate analysis, treatment success was found to be associated with young age, lack of cavitation and compliance with treatment.</p> <p>Conclusion</p> <p>The total treatment success rate in the current study was similar to the WHO target for all smear positive cases, while the failure rate and the default rate in 2002 were slightly higher. Good care of elderly patients, early diagnosis of cavitation and compliance with treatment could improve the success rate of TB treatment.</p

RIG-I contributes to the innate immune response after cerebral ischemia

BACKGROUND: Focal cerebral ischemia induces an inflammatory response that when exacerbated contributes to deleterious outcomes. The molecular basis regarding the regulation of the innate immune response after focal cerebral ischemia remains poorly understood. METHODS: In this study we examined the expression of retinoic acid-inducible gene (RIG)-like receptor-I (RIG-I) and its involvement in regulating inflammation after ischemia in the brain of rats subjected to middle cerebral artery occlusion (MCAO). In addition, we studied the regulation of RIG-I after oxygen glucose deprivation (OGD) in astrocytes in culture. RESULTS: In this study we show that in the hippocampus of rats, RIG-I and IFN-α are elevated after MCAO. Consistent with these results was an increased in RIG-I and IFN-α after OGD in astrocytes in culture. These data are consistent with immunohistochemical analysis of hippocampal sections, indicating that in GFAP-positive cells there was an increase in RIG-I after MCAO. In addition, in this study we have identified n-propyl gallate as an inhibitor of IFN-α signaling in astrocytes. CONCLUSION: Our findings suggest a role for RIG-I in contributing to the innate immune response after focal cerebral ischemia

Discovery of Pod Shatter-Resistant Associated SNPs by Deep Sequencing of a Representative Library Followed by Bulk Segregant Analysis in Rapeseed

Background: Single nucleotide polymorphisms (SNPs) are an important class of genetic marker for target gene mapping. As of yet, there is no rapid and effective method to identify SNPs linked with agronomic traits in rapeseed and other crop species. Methodology/Principal Findings: We demonstrate a novel method for identifying SNP markers in rapeseed by deep sequencing a representative library and performing bulk segregant analysis. With this method, SNPs associated with rapeseed pod shatter-resistance were discovered. Firstly, a reduced representation of the rapeseed genome was used. Genomic fragments ranging from 450–550 bp were prepared from the susceptible bulk (ten F2 plants with the silique shattering resistance index, SSRI,0.10) and the resistance bulk (ten F2 plants with SSRI.0.90), and also Solexa sequencingproduced 90 bp reads. Approximately 50 million of these sequence reads were assembled into contigs to a depth of 20-fold coverage. Secondly, 60,396 ‘simple SNPs ’ were identified, and the statistical significance was evaluated using Fisher’s exact test. There were 70 associated SNPs whose –log10p value over 16 were selected to be further analyzed. The distribution of these SNPs appeared a tight cluster, which consisted of 14 associated SNPs within a 396 kb region on chromosome A09. Our evidence indicates that this region contains a major quantitative trait locus (QTL). Finally, two associated SNPs from this region were mapped on a major QTL region

Hsp90 Inhibition Decreases Mitochondrial Protein Turnover

Cells treated with hsp90 inhibitors exhibit pleiotropic changes, including an expansion of the mitochondrial compartment, accompanied by mitochondrial fragmentation and condensed mitochondrial morphology, with ultimate compromise of mitochondrial integrity and apoptosis.We identified several mitochondrial oxidative phosphorylation complex subunits, including several encoded by mtDNA, that are upregulated by hsp90 inhibitors, without corresponding changes in mRNA abundance. Post-transcriptional accumulation of mitochondrial proteins observed with hsp90 inhibitors is also seen in cells treated with proteasome inhibitors. Detailed studies of the OSCP subunit of mitochondrial F1F0-ATPase revealed the presence of mono- and polyubiquitinated OSCP in mitochondrial fractions. We demonstrate that processed OSCP undergoes retrotranslocation to a trypsin-sensitive form associated with the outer mitochondrial membrane. Inhibition of proteasome or hsp90 function results in accumulation of both correctly targeted and retrotranslocated mitochondrial OSCP.Cytosolic turnover of mitochondrial proteins demonstrates a novel connection between mitochondrial and cytosolic compartments through the ubiquitin-proteasome system. Analogous to defective protein folding in the endoplasmic reticulum, a mitochondrial unfolded protein response may play a role in the apoptotic effects of hsp90 and proteasome inhibitors

Metabolic Profiles and cDNA-AFLP Analysis of Salvia miltiorrhiza and Salvia castanea Diel f. tomentosa Stib

Plants of the genus Salvia produce various types of phenolic compounds and tanshinones which are effective for treatment of coronary heart disease. Salvia miltiorrhiza and S. castanea Diels f. tomentosa Stib are two important members of the genus. In this study, metabolic profiles and cDNA-AFLP analysis of four samples were employed to identify novel genes potentially involved in phenolic compounds and tanshinones biosynthesis, including the red roots from the two species and two tanshinone-free roots from S. miltiorrhiza. The results showed that the red roots of S. castanea Diels f. tomentosa Stib produced high contents of rosmarinic acid (21.77 mg/g) and tanshinone IIA (12.60 mg/g), but low content of salvianolic acid B (1.45 mg/g). The red roots of S. miltiorrhiza produced high content of salvianolic acid B (18.69 mg/g), while tanshinones accumulation in this sample was much less than that in S. castanea Diels f. tomentosa Stib. Tanshinones were not detected in the two tanshinone-free samples, which produced high contents of phenolic compounds. A cDNA-AFLP analysis with 128 primer pairs revealed that 2300 transcript derived fragments (TDFs) were differentially expressed among the four samples. About 323 TDFs were sequenced, of which 78 TDFs were annotated with known functions through BLASTX searching the Genbank database and 14 annotated TDFs were assigned into secondary metabolic pathways through searching the KEGGPATHWAY database. The quantitative real-time PCR analysis indicated that the expression of 9 TDFs was positively correlated with accumulation of phenolic compounds and tanshinones. These TDFs additionally showed coordinated transcriptional response with 6 previously-identified genes involved in biosynthesis of tanshinones and phenolic compounds in S. miltiorrhiza hairy roots treated with yeast extract. The sequence data in the present work not only provided us candidate genes involved in phenolic compounds and tanshinones biosynthesis but also gave us further insight into secondary metabolism in Salvia

Angiopreventive Efficacy of Pure Flavonolignans from Milk Thistle Extract against Prostate Cancer: Targeting VEGF-VEGFR Signaling

The role of neo-angiogenesis in prostate cancer (PCA) growth and metastasis is well established, but the development of effective and non-toxic pharmacological inhibitors of angiogenesis remains an unaccomplished goal. In this regard, targeting aberrant angiogenesis through non-toxic phytochemicals could be an attractive angiopreventive strategy against PCA. The rationale of the present study was to compare the anti-angiogenic potential of four pure diastereoisomeric flavonolignans, namely silybin A, silybin B, isosilybin A and isosilybin B, which we established previously as biologically active constituents in Milk Thistle extract. Results showed that oral feeding of these flavonolignans (50 and 100 mg/kg body weight) effectively inhibit the growth of advanced human PCA DU145 xenografts. Immunohistochemical analyses revealed that these flavonolignans inhibit tumor angiogenesis biomarkers (CD31 and nestin) and signaling molecules regulating angiogenesis (VEGF, VEGFR1, VEGFR2, phospho-Akt and HIF-1α) without adversely affecting the vessel-count in normal tissues (liver, lung, and kidney) of tumor bearing mice. These flavonolignans also inhibited the microvessel sprouting from mouse dorsal aortas ex vivo, and the VEGF-induced cell proliferation, capillary-like tube formation and invasiveness of human umbilical vein endothelial cells (HUVEC) in vitro. Further studies in HUVEC showed that these diastereoisomers target cell cycle, apoptosis and VEGF-induced signaling cascade. Three dimensional growth assay as well as co-culture invasion and in vitro angiogenesis studies (with HUVEC and DU145 cells) suggested the differential effectiveness of the diastereoisomers toward PCA and endothelial cells. Overall, these studies elucidated the comparative anti-angiogenic efficacy of pure flavonolignans from Milk Thistle and suggest their usefulness in PCA angioprevention

Action Mechanism of Inhibin α-Subunit on the Development of Sertoli Cells and First Wave of Spermatogenesis in Mice

Inhibin is an important marker of Sertoli cell (SC) activity in animals with impaired spermatogenesis. However, the precise relationship between inhibin and SC activity is unknown. To investigate this relationship, we partially silenced both the transcription and translation of the gene for the α-subunit of inhibin, Inha, using recombinant pshRNA vectors developed with RNAi-Ready pSIREN-RetroQ-ZsGreen Vector (Clontech Laboratories, Mountain View, Calif). We found that Inha silencing suppresses the cell-cycle regulators Cyclin D1 and Cyclin E and up-regulates the cell-cycle inhibitor P21 (as detected by Western blot analysis), thereby increasing the number of SCs in the G1 phase of the cell cycle and decreasing the amount in the S-phase of the cell cycle (as detected by flow cytometry). Inha silencing also suppressed Pdgfa, Igf1, and Kitl mRNA levels and up-regulated Tgfbrs, Inhba, Inhbb, Cyp11a1, Dhh, and Tjp1 mRNA levels (as indicated by real-time polymerase chain reaction [PCR] analysis). These findings indicate that Inha has the potential to influence the availability of the ligand inhibin and its antagonist activin in the SC in an autocrine manner and inhibit the progression of SC from G1 to S. It may also participate in the development of the blood–testis barrier, Leydig cells, and spermatogenesis through its effect on Dhh, Tjp1, Kitl, and Pdgfa. Real-time PCR and Western blot analyses of Inha, Inhba, and Inhbb mRNA and Inha levels over time show that Inha plays an important role in the formation of round spermatid during the first wave of spermatogenesis in mice

Mesoporous Ternary Nitrides of Earth-Abundant Metals as Oxygen Evolution Electrocatalyst

As sustainable energy becomes a major concern for modern society, renewable and clean energy systems need highly active, stable, and low-cost catalysts for the oxygen evolution reaction (OER). Mesoporous materials offer an attractive route for generating efficient electrocatalysts with high mass transport capabilities. Herein, we report an efficient hard templating pathway to design and synthesize three-dimensional (3-D) mesoporous ternary nickel iron nitride (Ni3FeN). The as-synthesized electrocatalyst shows good OER performance in an alkaline solution with low overpotential (259 mV) and a small Tafel slope (54 mV dec(−1)), giving superior performance to IrO(2) and RuO(2) catalysts. The highly active contact area, the hierarchical porosity, and the synergistic effect of bimetal atoms contributed to the improved electrocatalytic performance toward OER. In a practical rechargeable Zn–air battery, mesoporous Ni(3)FeN is also shown to deliver a lower charging voltage and longer lifetime than RuO(2). This work opens up a new promising approach to synthesize active OER electrocatalysts for energy-related devices. [Image: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40820-020-0412-8) contains supplementary material, which is available to authorized users

A Modified Sagittal Spine Postural Classification and Its Relationship to Deformities and Spinal Mobility in a Chinese Osteoporotic Population

BACKGROUND: Abnormal posture and spinal mobility have been demonstrated to cause functional impairment in the quality of life, especially in the postmenopausal osteoporotic population. Most of the literature studies focus on either thoracic kyphosis or lumbar lordosis, but not on the change of the entire spinal alignment. Very few articles reported the spinal alignment of Chinese people. The purpose of this study was threefold: to classify the spinal curvature based on the classification system defined by Satoh consisting of the entire spine alignment; to identify the change of trunk mobility; and to relate spinal curvature to balance disorder in a Chinese population. METHODOLOGY/PRINCIPAL FINDINGS: 450 osteoporotic volunteers were recruited for this study. Spinal range of motion and global curvature were evaluated noninvasively using the Spinal-Mouse® system and sagittal postural deformities were characterized. RESULTS: We found a new spine postural alignment consisting of an increased thoracic kyphosis and decreased lumbar lordosis which we classified as our modified round back. We did not find any of Satoh's type 5 classification in our population. Type 2 sagittal alignment was the most common spinal deformity (38.44%). In standing, thoracic kyphosis angles in types 2 (58.34°) and 3 (58.03°) were the largest and lumbar lordosis angles in types 4 (13.95°) and 5 (-8.61°) were the smallest. The range of flexion (ROF) and range of flexion-extension (ROFE) of types 2 and 3 were usually greater than types 4 and 5, with type 1 being the largest. CONCLUSIONS/SIGNIFICANCE: The present study classified and compared for the first time the mobility, curvature and balance in a Chinese population based on the entire spine alignment and found types 4 and 5 to present the worst balance and mobility. This study included a new spine postural alignment classification that should be considered in future population studies

Amyloid Precursor Protein Is Trafficked and Secreted via Synaptic Vesicles

A large body of evidence has implicated amyloid precursor protein (APP) and its proteolytic derivatives as key players in the physiological context of neuronal synaptogenesis and synapse maintenance, as well as in the pathology of Alzheimer's Disease (AD). Although APP processing and release are known to occur in response to neuronal stimulation, the exact mechanism by which APP reaches the neuronal surface is unclear. We now demonstrate that a small but relevant number of synaptic vesicles contain APP, which can be released during neuronal activity, and most likely represent the major exocytic pathway of APP. This novel finding leads us to propose a revised model of presynaptic APP trafficking that reconciles existing knowledge on APP with our present understanding of vesicular release and recycling