Explore the vast range of titles available.

Background This study examines global trends in acquired immune deficiency syndrome (AIDS) incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2019, focusing on regional disparities in AIDS incidence, mortality, and DALYs across various levels of socio-demographic index (SDI). It also investigates variations in AIDS incidence, mortality, and DALYs across different age groups, and projects specific trends for the next 25 years. Methods Comprehensive data on AIDS from 1990 to 2019 in 204 countries and territories was obtained from a GBD study. This included information on AIDS incidence, mortality, DALYs, and age-standardized rates (ASRs). Projections for AIDS incidence and mortality over the next 25 years were generated using the Bayesian age-period-cohort model. Results From 1990 to 2019, the global incidence of HIV cases increased from 1,989,282 to 2,057,710, while the age-standardized incidence rate (ASIR) decreased from 37.59 to 25.24 with an estimated annual percentage change (EAPC) of -2.38. The ASIR exhibited an upward trend in high SDI and high-middle SDI regions, a stable trend in middle SDI regions, and a downward trend in low-middle SDI and low SDI regions. In regions with higher SDI, the ASIR was higher in males than in females, while the opposite was observed in lower SDI regions. Throughout 1990 to 2019, the age-standardized death rate (ASDR) and age-standardized DALY rate remained stable, with EAPCs of 0.24 and 0.08 respectively. Countries with the highest HIV burden affecting women and children under five years of age are primarily situated in lower SDI regions, particularly in sub-Saharan Africa. Projections indicate a significant continued decline in the age-standardized incidence and mortality rates of AIDS over the next 25 years, for both overall and by gender. Conclusions The global ASIR decreased from 1990 to 2019. Higher incidence and death rates were observed in the lower SDI region, indicating a greater susceptibility to AIDS among women and < 15 years old. This underscores the urgent need for increased resources to combat AIDS in this region, with focused attention on protecting women and < 15 years old as priority groups. The AIDS epidemic remained severe in sub-Saharan Africa. Projections for the next 25 years indicate a substantial and ongoing decline in both age-standardized incidence and mortality rates.

Two kinds of ultra-high strength cold rolled dual phase steels have been developed by designing C-Si-Mn-Cr and C-Si-Mn-Cr-Mo alloy systems. Tensile strength and elongation of both steels exceed 1100 MPa and 10%,respectively. The microstructures of both steels consist of massive martensite and ferrite. And the massive martensite of Mo-free steel disperses in the ferrite with volume fraction of 64%. However,the massive martensite of Mo-containing steel is connected or closed by small martensite islands each other,and martensite volume fraction is 69%. As to Mo-free steel,the yield strength,yield ratio,and work hardening exponent n are 548 MPa,0.49,and 0.26,respectively. As for Mo-containing one,the yield strength,yield ratio,and n value are 746 MPa,0.66,and 0.33,respectively. Besides,the ferrite of Mo-free steel is deformed at the initial stage of plastic deformation. However,for Mo-containing one,Mo solution strengthened ferrite and small overaged martensite islands are deformed preferentially at small strain,which causes the yield strength to reach approximately 200 MPa higher than that of Mo-free steel.

The high-temperature mechanical properties and microstructure of forging billets of C-Si-Mn-Cr and C-Si-Mn-Cr-Mo ultra-high-strength cold-rolled steels（tensile strength≥1000 MPa,elongation≥10%） were studied.Through the comparison of reduction in area and hot deformation resistance at 600-1300°C,the Mo-containing steel was found to possess a higher strength and a better plasticity than the Mo-free one.The equilibrium phase diagram and atom fraction of Mo in different phases at different temperatures were calculated by Thermo-Calc software（TCW）.The results analyzed by using transmission electron microscopy and TCW show that precipitates in the Mo-containing steel are primarily M23C6,which promote pearlite formation.The experimental data also show that a lower ductility point existing in the Mo-free steel at 850°C is eliminated in the Mo-containing one.This is mainly due to the segregation of Mo at grain boundaries investigated by electron probe microanalysis（EPMA）,which improves the strength of grain boundaries.

The morphology of manganese sulfide formed during thin slab continuous casting process in low-carbon steel produced by compact strip production （CSP） technique was investigated. Using transmission electron microscopy analysis, it was seen that a majority of manganese sulfides precipitated at austenite grain boundaries, the morphologies of which were spherical or close to the spherical shape and the size of MnS precipitates ranged from 30 nm to 100 nm. A mathematical model of the manganese sulfide precipitation in this process was developed based on classical nucleation theory. Under the given conditions, the starting and finishing precipitation temperatures of MnS in the continuous casting thin slab of the studied low-carbon steel are 1 189 ℃ and 1 171 ℃, respectively, and the average diameter of MnS precipitates is about 48 nm within this precipitation temperature range. The influences of chemical components and thermo-mechanical processing conditions on the precipitation behavior of MnS in the same process were also discussed.

Aim： To investigate the effects of the transducer of ErbB-2.1 （TOB1） on the proliferation, migration and invasion of human lung cancer cells in vitro. Methods： Human lung cancer cell lines （95-D, A549, NCI-H1299, NCI-H1975, NCI-H661, NCI-H446, NCI-H1395, and Calu-3） and the normal human bronchial epithelial （HBE） cell line were tested. The expression levels of TOB1 in the cells were determined with Western blot and RT-PCR analyses. TOBl-overexpressing cell line 95-D/TOB1 was constructed using lipofectamine-induced TOB1 recombinant plasmid transfection and selective G418 cell culture. The A549 cells were transcend-transfected with TOBI-siRNA. MTT assay, flow cytometry and Western blot analysis were used to examine the effects of TOB1 on cancer cell proliferation and wound healing. Transwell invasive assay was performed to evaluate the effects of TOB1 on cancer cell migration and invasion. The activity of MMP2 and MMP9 was measured using gelatin zymography assay. Results： The expression levels of TOB1 in the 8 human lung cancer cell lines were significantly lower than that in HBE cells. TOB1 overexpression inhibited the proliferation of 95-D cells, whereas TOB1 knockdown with TOBI-siRNA promoted the growth of A549 cells. Decreased cell migration and invasion were detected in 95-D/TOB1 cells, and the suppression of TOB1 enhanced the metastasis in A549 cells. TOB1 overexpression not only increased the expression of the phosphatase and tensin homolog （PTEN）, an important tumor suppressor, but also regulated the downstream effectors in the PI3K/PTEN signaling pathway, including Akt, ERK1/2, etc. In contrast, decreased expression of TOB1 oppositely regulated the expression of these factors. TOB1 also regulates the gelatinase activity of MMP2 and MMP9 in lung cancer cells. Conclusion： The results demonstrate that the PI3K/PTEN pathway, which is essential for carcinogenesis, angiogenesis, and metastasis, may be one of the possible signaling pathways for regulation of proliferation and metastasis of human lung cancer cells by TOB1 in vitro.

Objectives To assess the mutation effects of ethambutol (EMB) resistance-associated genes, including embCAB operon, ubiA , embR , and aftA , on the EMB resistance levels among multidrug-resistant tuberculosis (MDR-TB) isolates from China. Methods A total of 159 MDR-TB from China had their EMB MICs quantified, and the sequences of the four ethambutol resistance-associated regions were analyzed. A multivariate regression model was established to evaluate the effects of mutations on EMB resistance. Results Our results showed that overall 95.6% (109/114 isolates) of EMB-resistant isolates harbored at least one mutation within the regions associated with EMB resistance. Most mutations were in embB , particularly in the embB 300-500, and the embC-embA intergenic regions. Mutations in other genes were seldom seen and mainly occurred along with mutations in the embB or the embC-embA among the EMB-resistant isolates. DNA sequencing of the embB 300-500 and the embC-embA was the most effective approach for detecting EMB resistance, with an accuracy of 91.2%. Nevertheless, some EMB-susceptible isolates still had a single mutation in the gene related to EMB resistance. Moreover, there was a significant correlation between EMB high-level resistance and multiple mutations. Conclusion Distinct individual mutations, as well as multiple concurrent mutations, within EMB resistance-associated genes, contributed to variable levels of EMB resistance. These results have broadened our understanding of the molecular characteristics of EMB resistance in China.

Aim： The herbal prescription Chang＇an Ⅱ is derived from a classical TCM formula Tong-Xie-Yao-Fang for the treatment of liver-qi stagnation and spleen deficiency syndrome of irritable bowel syndrome （IBS）. In this study we investigated the effects of Chang＇an II on the intestinal mucosal immune barrier in a rat post-inflammation IBS （PI-IBS） model. Methods： A rat model of PI-IBS was established using a multi-stimulation paradigm including early postnatal sibling deprivation, bondage and intrarectal administration of TNBS. Four weeks after TNBS administration, the rats were treated with Chang＇an Ⅱ（2.85, 5.71 and 11.42 g·kg^-1·d^-1, ig） for 14 d. Intestinal sensitivity was assessed based on the abdominal withdrawal reflex （AWR） scores and fecal water content. Open field test and two-bottle sucrose intake test were used to evaluate the behavioral changes. CD4^＋ and CD8^＋ cells were counted and IL-1β and IL-4 levels were measured in intestinal mucosa. Transmission electron microscopy was used to evaluate ultrastructural changes of the intestinal mucosal barrier. Results： PI-IBS model rats showed significantly increased AWR reactivity and fecal water content, and decreased locomotor activity and sucrose intake. Chang＇an II treatment not only reduced AWR reactivity and fecal water content, but also suppressed the anxiety and depressive behaviors. Ultrastructural study revealed that the gut mucosal barrier function was severely damaged in PI-IBS model rats, whereas Chang＇an II treatment relieved intestinal mucosal inflammation and repaired the gut mucosal barrier. Furthermore, PI-IBS model rats showed a significantly reduced CD4＋^/CD8^＋ cell ratio in lamina propria and submucosa, and increased IL-1β and reduced IL-4 expression in intestinal mucosa, whereas Chang＇an Ⅱ treatment reversed PI-IBS-induced changes in CD4^＋/CD8^＋ cell ratio and expression of IL-1β and IL-4. Conclusion： Chang＇an Ⅱ treatment protects the intestinal mucosa against PI-IBS through anti-inflammatory, immunomodulatory and anti-anxiety effects.

To investigate the mutations within the whole gene of and analyze their effects on rifampin (RIF) resistance based on crystal structure. We sequenced the entire gene in 175 tuberculosis isolates and quantified their minimum inhibitory concentrations using microplate-based assays. Additionally, the structural interactions between wild-type/mutant RpoB and RIF were also analyzed. Results revealed that a total of 34 mutations distributed across 17 different sites within the whole gene were identified. Of the 34 mutations, 25 could alter the structural interaction between RpoB and RIF and contribute to RIF resistance. Statistical analysis showed that S450L, H445D, H445Y and H445R mutations were associated with high-level RIF resistance, while D435V was associated with moderate-level RIF resistance. Some mutations within the gene could affect the interaction between RpoB and RIF and thus are associated with RIF resistance. These findings could be helpful to design new antibiotics and develop novel diagnostic tools for drug resistance in TB.

Photoacid generators (PAGs) are compounds capable of producing hydrogen protons (H+) upon irradiation, including irreversible and reversible PAGs, which have been widely studied in photoinduced polymerization and degradation for a long time. In recent years, the applications of PAGs in the biomedical field have attracted more attention due to their promising clinical value. So, an increasing number of novel PAGs have been reported. In this review, the recent progresses of PAGs for biomedical applications is systematically summarized, including tumor treatment, antibacterial treatment, regulation of protein folding and unfolding, control of drug release and so on. Furthermore, a concept of water‐dependent reversible photoacid (W‐RPA) and its antitumor effect are highlighted. Eventually, the challenges of PAGs for clinical applications are discussed. With the growing demand for biomaterials, many PAGs have been designed and synthetized for biomedical applications. Here, the recent progresses of PAGs for tumor treatment is summarized, antibacterial treatment, regulation of protein folding and unfolding, control of drug release and so on. Furthermore, W‐RPA and its applications are highlighted. Finally, the challenges of PAGs for clinical applications are discussed.

Oxidative phosphorylation (OXPHOS) in the mitochondrial inner membrane is a therapeutic target in many diseases. Neural stem cells (NSCs) show progress in improving mitochondrial dysfunction in the central nervous system (CNS). However, translating neural stem cell-based therapies to the clinic is challenged by uncontrollable biological variability or heterogeneity, hindering uniform clinical safety and efficacy evaluations. We propose a systematic top-down design based on membrane self-assembly to develop neural stem cell-derived oxidative phosphorylating artificial organelles (SAOs) for targeting the central nervous system as an alternative to NSCs. We construct human conditionally immortal clone neural stem cells (iNSCs) as parent cells and use a streamlined closed operation system to prepare neural stem cell-derived highly homogenous oxidative phosphorylating artificial organelles. These artificial organelles act as biomimetic organelles to mimic respiration chain function and perform oxidative phosphorylation, thus improving ATP synthesis deficiency and rectifying excessive mitochondrial reactive oxygen species production. Conclusively, we provide a framework for a generalizable manufacturing procedure that opens promising prospects for disease treatment. Regulating oxidative phosphorylation and restoring redox homeostasis are crucial in neurological disorders. Here, the authors develop a top-down membrane self-assembly strategy to develop stem cell-derived artificial organelles (SAOs) that mimic mitochondrial oxidative phosphorylation without the risks associated with stem cell therapy.