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Abstract Based on the disaster-pregnant environment and development characteristics of landslide disasters in the western region of Henan Province, a generalized model was established by taking the “oblique-cut” locking rock slope in the layered rock slope as the research object. The numerical simulation method was used to analyze the deformation and failure mechanism and stability influence law of the oblique-cut locking rock slope in western Henan under rainfall conditions. The results show that the inclination angle of the weak interlayer directly affects the deformation and failure characteristics of the slope rock mass. With the increase of the geometric parameters of the slope and the inclination angle of the weak interlayer, the failure mechanism is manifested as the slip shear failure along the level at the foot of the slope → the slip shear failure along the level at the foot of the slope (the sliding surface moves upward) → the shear failure in the middle of the slope surface → the slip shear failure along the level at the foot of the slope (the sliding surface moves downward) → the uplift shear failure at the lower edge of the rock layer. When the dip angle of the weak interlayer is constant, the slope stability decreases gradually with the increase in slope gradient and slope height, and the geometric factors of the slope control the overall change trend of the slope stability coefficient. When the slope is greater than 55° and the slope height is greater than 55 m, the shear stress of the slope locking section exceeds its shear strength, and the probability of landslide instability is greatly increased.

Abstract The causal association between vitamin E status and osteoarthritis (OA) remains controversial in previous epidemiological studies. We employed a Mendelian randomization (MR) analysis to explore the causal relationship between circulating alpha-tocopherol levels (main forms of vitamin E in our body) and OA. The instrumental variables (IVs) of circulating alpha-tocopherol levels were obtained from a Genome-wide association study (GWAS) dataset of 7781 individuals of European descent. The outcome of OA was derived from the UK biobank. Two-sample MR analysis was used to estimate the causal relationship between circulating alpha-tocopherol levels and OA. The inverse-variance weighted (IVW) method was the primary analysis in this analysis. We used the MR-Egger method to determine horizontal pleiotropic in this work. The heterogeneity effect of instrumental IVs was detected by MR-Egger and IVW analyses. Sensitivity analysis was performed by removing single nucleotide polymorphism (SNP) one by one. Three SNPs (rs964184, rs2108622, and rs11057830) (P

Abstract. Background:. T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), an inhibitory receptor expressed on T cells, plays a dysfunctional role in antiviral infection and antitumor activity. However, it is unknown whether TIGIT expression on T cells influences the immunological effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inactivated vaccines. Methods:. Forty-five people living with HIV (PLWH) on antiretroviral therapy (ART) for more than two years and 31 healthy controls (HCs), all received a third dose of a SARS-CoV-2 inactivated vaccine, were enrolled in this study. The amounts, activation, proportion of cell subsets, and magnitude of the SARS-CoV-2-specific immune response of TIGIT+CD4+ and TIGIT+CD8+ T cells were investigated before the third dose but 6 months after the second vaccine dose (0W), 4 weeks (4W) and 12 weeks (12W) after the third dose. Results:. Compared to that in HCs, the frequency of TIGIT+ CD8+ T cells in the peripheral blood of PLWH increased at 12W after the third dose of the inactivated vaccine, and the immune activation of TIGIT+CD8+ T cells also increased. A decrease in the ratio of both T naïve (TN) and central memory (TCM) cells among TIGIT+CD8+ T cells and an increase in the ratio of the effector memory (TEM) subpopulation were observed at 12W in PLWH. Interestingly, particularly at 12W, a higher proportion of TIGIT+CD8+ T cells expressing CD137 and CD69 simultaneously was observed in HCs than in PLWH based on the activation-induced marker assay. Compared with 0W, SARS-CoV-2-specific TIGIT+CD8+ T-cell responses in PLWH were not enhanced at 12W but were enhanced in HCs. Additionally, at all time points, the SARS-CoV-2-specific responses of TIGIT+CD8+ T cells in PLWH were significantly weaker than those of TIGIT-CD8+ T cells. However, in HCs, the difference in the SARS-CoV-2-specific responses induced between TIGIT+CD8+ T cells and TIGIT-CD8+ T cells was insignificant at 4W and 12W, except at 0W. Conclusions:. TIGIT expression on CD8+ T cells may hinder the T-cell immune response to a booster dose of an inactivated SARS-CoV-2 vaccine, suggesting weakened resistance to SARS-CoV-2 infection, especially in PLWH. Furthermore, TIGIT may be used as a potential target to increase the production of SARS-CoV-2-specific CD8+ T cells, thereby enhancing the effectiveness of vaccination.

Abstract. Background:. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine can induce a potent cellular and humoral immune response to protect against SARS-CoV-2 infection. However, it was unknown whether SARS-CoV-2 vaccination can induce effective natural killer (NK) cell response in people living with human immunodeficiency virus (PLWH) and healthy individuals. Methods:. Forty-seven PLWH and thirty healthy controls (HCs) inoculated with SARS-CoV-2 inactivated vaccine were enrolled from Beijing Youan Hospital in this study. The effect of SARS-CoV-2 vaccine on NK cell frequency, phenotype, and function in PLWH and HCs was evaluated by flow cytometry, and the response of NK cells to SARS-CoV-2 Omicron Spike (SARS-2-OS) protein stimulation was also evaluated. Results:. SARS-CoV-2 vaccine inoculation elicited activation and degranulation of NK cells in PLWH, which peaked at 2 weeks and then decreased to a minimum at 12 weeks after the third dose of vaccine. However, in vitro stimulation of the corresponding peripheral blood monocular cells from PLWH with SARS-2-OS protein did not upregulate the expression of the aforementioned markers. Additionally, the frequencies of NK cells expressing the activation markers CD25 and CD69 in PLWH were significantly lower than those in HCs at 0, 4 and 12 weeks, but the percentage of CD16+ NK cells in PLWH was significantly higher than that in HCs at 2, 4 and 12 weeks after the third dose of vaccine. Interestingly, the frequency of CD16+ NK cells was significantly negatively correlated with the proportion of CD107a+ NK cells in PLWH at each time point after the third dose. Similarly, this phenomenon was also observed in HCs at 0, 2, and 4 weeks after the third dose. Finally, regardless of whether NK cells were stimulated with SARS-2-OS or not, we did not observe any differences in the expression of NK cell degranulation markers between PLWH and HCs. Conclusion:. s:SARS-CoV-2 vaccine elicited activation and degranulation of NK cells, indicating that the inoculation of SARS-CoV-2 vaccine enhances NK cell immune response.

Abstract. Although antiretroviral therapy (ART) can reduce the viral load in the plasma to undetectable levels in human immunodeficiency virus (HIV)-infected individuals, ART alone cannot completely eliminate HIV due to its integration into the host cell genome to form viral reservoirs. To achieve a functional cure for HIV infection, numerous preclinical and clinical studies are underway to develop innovative immunotherapies to eliminate HIV reservoirs in the absence of ART. Early studies have tested adoptive T-cell therapies in HIV-infected individuals, but their effectiveness was limited. In recent years, with the technological progress and great success of chimeric antigen receptor (CAR) therapy in the treatment of hematological malignancies, CAR therapy has gradually shown its advantages in the field of HIV infection. Many studies have identified a variety of HIV-specific CAR structures and types of cytolytic effector cells. Therefore, CAR therapy may be beneficial for enhancing HIV immunity, achieving HIV control, and eliminating HIV reservoirs, gradually becoming a promising strategy for achieving a functional HIV cure. In this review, we provide an overview of the design of anti-HIV CAR proteins, the cell types of anti-HIV CAR (including CAR T cells, CAR natural killer cells, and CAR-encoding hematopoietic stem/progenitor cells), the clinical application of CAR therapy in HIV infection, and the prospects and challenges in anti-HIV CAR therapy for maintaining viral suppression and eliminating HIV reservoirs.

Abstract. Over the past few years, the human virome and its complex interactions with microbial communities and the immune system have gained recognition as a crucial factor in human health. Individuals with compromised immune function encounter distinctive challenges due to their heightened vulnerability to a diverse range of infectious diseases. This review aims to comprehensively explore and analyze the growing evidence regarding the role of the virome in immunocompromised disease status. By surveying the latest literature, we present a detailed overview of virome alterations observed in various immunodeficiency conditions. We then delve into the influence and mechanisms of these virome changes on the pathogenesis of specific diseases in immunocompromised individuals. Furthermore, this review explores the clinical relevance of virome studies in the context of immunodeficiency, highlighting the potential diagnostic and therapeutic gains from a better understanding of virome contributions to disease manifestations.

Abstract Although bisphenol S (BPS), as a bisphenol A (BPA) substitute, has been widely used in the commodity, it is embryotoxic in recent experiments. Nowadays, it remains unclear how BPS affects preimplantation embryos. Here, my team investigated the effects of BPS on preimplantation embryos and the possible molecular mechanisms in mice. The results showed that 10–6 mol/L BPS exposure delayed the blastocysts stage, and exposure to 10–4 mol/L BPS induced 2-cell block in mice preimplantation embryos. A significant increase in reactive oxygen species (ROS) level and antioxidant enzyme genes Sod1, Gpx1, Gpx6, and Prdx2 expression were shown, but the level of apoptosis was normal in 2-cell blocked embryos. Further experiments demonstrated that embryonic genome activation (EGA) specific genes Hsp70.1 and Hsc70 were significantly decreased, which implied that ROS and EGA activation have the potential to block 2-cell development. Antioxidant enzymes, including superoxide dismutase (SOD), coenzyme Q10 (CoQ10), and folic acid (FA) were used to further explore the roles of ROS and EGA in 2-cell block. Only 1200 U/mL SOD was found to alleviate the phenomenon of 2-cell block, reduce oxidative damage, and restore the expression of EGA-specific genes Hsp70.1 and Hsc70. Conclusively, this study demonstrates for the first time that BPS can induce 2-cell block, which is mainly mediated by ROS aggregation and results in the failure of EGA activation.

Abstract Genomic information on alfalfa adaptation to long-term grazing is useful for alfalfa genetic improvement. In this study, 14 alfalfa populations were collected from long-term grazing sites (> 25 years) across four soil zones in western Canada. Alfalfa cultivars released between 1926 and 1980 were used to compare degree of genetic variation of the 14 populations. Six agro-morphological and three nutritive value traits were evaluated from 2018 to 2020. The genotyping-by-sequencing (GBS) data of the alfalfa populations and environmental data were used for genotype-environment association (GEA). Both STRUCTURE and UPGMA based on 19,853 SNPs showed that the 14 alfalfa populations from long-term grazing sites had varying levels of parentages from alfalfa sub-species Medicago sativa and M. falcata. The linear regression of STRUCTURE membership probability on phenotypic data indicated genetic variations of forage dry matter yield, spring vigor and plant height were low, but genetic variations of regrowth, fall plant height, days to flower and crude protein were still high for the 14 alfalfa populations from long-term grazing sites. The GEA identified 31 SNPs associated with 13 candidate genes that were mainly associated with six environmental factors of. Candidate genes underlying environmental factors were associated with a variety of proteins, which were involved in plant responses to abiotic stresses, i.e., drought, cold and salinity-alkali stresses.

Abstract Background Radiotherapy is the primary therapeutic option for glioblastoma. Some studies proved that radiotherapy increased the release of exosomes from cells. The mechanism by which these exosomes modify the phenotype of microglia in the tumor microenvironment to further determine the fate of irradiated glioblastoma cells remains to be elucidated. Methods We erected the co-culture system of glioblastoma cells and microglia. After radiation, we analyzing the immunophenotype of microglia and the proliferation of radiated glioblastoma cells. By whole transcriptome sequencing, we analyzed of circRNAs in exosomes from glioblastoma cells and microglia. We used some methods, which included RT-PCR, dual-luciferase reporter, et al., to identify how circ_0012381 from radiated glioblastoma cell-derived exosomes regulated the immunophenotype of microglia to further affect the proliferation of radiated glioblastoma cells. Results Radiated glioblastoma cell-derived exosomes markedly induced M2 microglia polarization. These M2-polarized microglia promoted the proliferation of irradiated glioblastoma cells. Circ_0012381 expression was increased in the irradiated glioblastoma cells, and circ_0012381 entered the microglia via exosomes. Circ_0012381 induced M2 microglia polarization by sponging with miR-340-5p to increase ARG1 expression. M2-polarized microglia suppressed phagocytosis and promoted the growth of the irradiated glioblastoma cells by CCL2/CCR2 axis. Compared with the effects of radiotherapy alone, the inhibition of exosomes significantly inhibited the growth of irradiated glioblastoma cells in a zebrafish model. Conclusions Our data suggested that the inhibition of exosome secretion might represent a potential therapeutic strategy to increase the efficacy of radiotherapy in patients with glioblastoma.

BackgroundCoffee is the most commonly consumed beverage among children and adolescences. Caffeine was demonstrated to be associated with bone metabolism. However, the relationship between caffeine intake and BMD in children and adolescents remains unclear. This study aimed to identified relationship between caffeine consumption and bone mineral density (BMD) in children and adolescents.MethodsBased on National Health and Nutrition Examination Survey (NHANES), we conducted an epidemiological cross-section study to measure the relationship between caffeine consumption and BMD in children and adolescents by multivariate linear regression models. Then, five methods of Mendelian randomization (MR) analyses were performed to estimate their causal relationship between coffee and caffeine intake and BMD in children and adolescents. MR-Egger and inverse-variance weighted (IVW) were used to evaluate the heterogeneity effect of instrumental variables (IVs).ResultsIn epidemiological studies, individuals with the highest quartile of caffeine intake do not have a significant change in femur neck BMD (β = 0.0016, 95% CI: -0.0096, 0.0129, P = 0.7747), total femur BMD (β = 0.0019, P = 0.7552), and total spine BMD (β = 0.0081, P = 0.1945) compared with the lowest quartile. In MR analysis, the IVW-random effect indicates no causal relationship between coffee consumption and TB- BMD (β = 0.0034, P = 0.0910). Other methods of MR analyses and sensitivity analysis reveals consistent findings. Similarly, the fixed-effects IVW method shows no causal association between caffeine intake and TB-BMD in children and adolescents (β = 0.0202, P = 0.7828).ConclusionsOur study does not support a causal relationship between caffeine consumption and BMD in children and adolescents. However, more studies are needed to verify our findings, such as its underlying molecular mechanisms and the long-term impact of early caffeine exposure at a younger age.

IntroductionIn spine surgery, poor bone condition is associated with several complications like adjacent segment fractures, proximal junctional kyphosis, and screw loosening. Our study explored the prevalence of osteoporosis in spinal surgery patients older than 50 years through a systematic review and meta-analysis.MethodsThis systematic review and meta-analysis were conducted according to the PRISMA criteria. Three electronic databases, including PubMed, EMBASE, and Web of Science, were searched from inception to August 2022. We used the random-effects model to calculate the overall estimates, and the heterogeneity was measured using Cochran's Q and I2 tests. Meta-regression and subgroup analyses were used to determine the source of the heterogeneity.ResultsBased on the inclusion and criteria, we chose ten studies with 2958 individuals for our analysis. The prevalence of osteoporosis, osteopenia, and osteoporosis/osteopenia in the spinal surgery patients was 34.2% (95%CI: 24.5%-44.6%), 43.5% (95%CI: 39.8%-47.2%), and 78.7% (95%CI: 69.0%-87.0%), respectively. Regarding different diagnoses, the prevalence was highest in patients with lumbar scoliosis (55.8%; 95%CI: 46.8%-64.7%) and the lowest in patients with cervical disc herniation (12.9%; 95%CI: 8.1%-18.7%). In age groups 50-59, 50-69,70-79, the prevalence was 27.8%, 60.4%, 75.4% in females, and 18.9%, 17.4%, 26.1% in males.ConclusionsThis study showed a high prevalence of osteoporosis in patients undergoing spine surgery, especially in females, people of older age, and patients who received degenerative scoliosis and compression fractures. Current osteoporosis screening standards for patients undergoing spine surgery may not be adequate. Orthopedic specialists should make more efforts regarding preoperative osteoporosis screening and treatment.

IntroductionBone mineral density (BMD) in adolescence is a crucial determinant in osteoporosis and fragility fractures in older age. Vitamin E is the most abundant lipid-soluble antioxidant present in the blood. However, the association of vitamin E status with BMD in children and adolescents remains unclear.MethodsWe first measured the association of vitamin E status (serum α- and γ tocopherol) with BMD in children and adolescents with the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression models were performed to evaluate their relationship after adjusting for a large range of covariates. Stratified analyses and interaction tests were used to explore their effects on different genders, ages, and races/ethnicities.Results13,606 children and adolescents from NHANES (2005-2006, 2017-2018) were included in our analysis. Compared with the lowest α-tocopherol quartile, individuals in the highest α-tocopherol quartile are likelier to be Non-Hispanic White and have a higher value of poverty income ratio (PIR). They have a lower value of serum phosphorus and lumbar spine BMD. Every 1umol/L increase in serum α- and γ- tocopherol, the lumbar spine BMD decreased by -0.0016 and -0.0068 g/cm2. Compared with the lowest quartile serum α- and γ- tocopherol concentration, individuals in the highest quartile have a -0.0223 and -0.0329 g/cm2 lower mean BMD, respectively. Interaction effects suggest that the negative effect is more prominent among female youth, individuals aged 8-13 years, non-Hispanic whites, Mexican Americans, and non-Hispanic blacks.ConclusionsOur study indicates serum α- and γ-tocopherol are negatively correlated with lumbar BMD. Age, gender, and race may have a modifying effect on this relationship. Our study has an important clinical implication. A higher vitamin E status for children and adolescents could not improve BMD, even decrease BMD. More prospective research with stronger evidence is needed to verify our findings and their underlying mechanisms.

Abstract Remarkable progress in ageing research has been achieved over the past decades. General perceptions and experimental evidence pinpoint that the decline of physical function often initiates by cell senescence and organ ageing. Epigenetic dynamics and immunometabolic reprogramming link to the alterations of cellular response to intrinsic and extrinsic stimuli, representing current hotspots as they not only (re-)shape the individual cell identity, but also involve in cell fate decision. This review focuses on the present findings and emerging concepts in epigenetic, inflammatory, and metabolic regulations and the consequences of the ageing process. Potential therapeutic interventions targeting cell senescence and regulatory mechanisms, using state-of-the-art techniques are also discussed.

Abstract Background Calcium oxalate (CaOx), the major constituent of most kidney stones, induces inflammatory infiltration and injures renal tubular cells. However, the role of γδT cells in CaOx-mediated kidney injury remains unclear. Therefore, this study investigated the distribution of intrarenal γδT cells and T cell receptor δ (TCRδ) immune repertoires in response to interactions with CaOx crystals. Methods CaOx crystal mouse model was established by glyoxylate injection. Flow cytometer was used to analyze the expression of CD69 and IL-17 from intrarenal γδT cells. Furthermore, TCR immune repertoire sequencing (IR-Seq) was used to monitor the profile of the TCRδ immune repertoire. Results Our results indicated that CaOx crystals lead to obvious increases in the expression and activation of intrarenal γδT cells. In TCRδ immune repertoire, the majority of V/J gene and V–J/V–D–J combination segments, barring individual exceptions, were similar between kidneys with CaOx formation and control kidneys. Impressively, high complementarity determining region 3 (CDR3) diversity was observed in response to CaOx crystal formation along with distinct CDR3 distribution and abundance. Conclusion Our work suggests the presence of aberrant γδT cell activation and reconstitution of the TCRδ immune repertoire in response to CaOx crystal deposition.

Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis in Asia, and vaccination is the most effective way to prevent JE. Although several licensed vaccines were widely used, there is still a demand for developing safer, cheaper, and more effective JE vaccines. In the current study, a virus-like particle (VLP) vaccine candidate containing the envelope structural protein of JEV expressed by the Pichia pastoris was assembled in vitro. It elicited a robust humoral and cellular immune response in mice model, conferring immunodeficient mice complete protection against lethal doses of JEV challenge. Furthermore, pigs immunized with VLP alone without adjuvant via intramuscular produced high neutralizing antibodies against JEV. Consequently, this study showed a new design of JEV subunit vaccine based on VLP strategy and demonstrated the potential for clinical application.

Leaf tooth can indicate several systematically informative features and is extremely useful for circumscribing fossil leaf taxa. Moreover, it can help discriminate species or even higher taxa accurately. Previous studies extract features that are not strictly defined in botany; therefore, a uniform standard to compare the accuracies of various feature extraction methods cannot be used. For efficient and automatic retrieval of plant leaves from a leaf database, in this study, we propose an image-based description and measurement of leaf teeth by referring to the leaf structure classification system in botany. First, image preprocessing is carried out to obtain a binary map of plant leaves. Then, corner detection based on the curvature scale-space (CSS) algorithm is used to extract the inflection point from the edges; next, the leaf tooth apex is extracted by screening the convex points; then, according to the definition of the leaf structure, the characteristics of the leaf teeth are described and measured in terms of number of orders of teeth, tooth spacing, number of teeth, sinus shape, and tooth shape. In this manner, data extracted from the algorithm can not only be used to classify plants, but also provide scientific and standardized data to understand the history of plant evolution. Finally, to verify the effectiveness of the extraction method, we used simple linear discriminant analysis and multiclass support vector machine to classify leaves. The results show that the proposed method achieves high accuracy that is superior to that of other methods.

Background: Takayasu arteritis (TA) is a rare inflammatory arteriopathy of unknown etiology. The aim of this study was to investigate the genetic susceptibility to TA in a Chinese population. Methods: Four single nucleotide polymorphisms (SNPs) those locate in the IL12B region (rs56167332), the MLX region (rs665268), the FCGR2A/FCGR3A locus (rs10919543), and the HLA-B/MICA locus (rs12524487), associated with TA in different population, were genotyped in 123 Chinese TA patients and 147 healthy controls from January 2013 to August 2014. A Chi-square test was used to test for genotype/allele frequencies variants. Results: Among the four SNPs, rs10919543 was found to be significantly associated with TA in the studied population. The GG genotype of rs10919543 at the FCGR2A/FCGR3A locus is a high risk factor (odds ratio [OR] = 6.532, 95% confidence interval [CI] = 2.402 − 17.763, P < 0.001) for TA. Among TA patients, the level of eosinophil granulocytes (Eos) in the peripheral blood was observed to be higher in the GG group of rs10919543 (n = 23, Eos = 0.11 [0.08, 0.17] ×109/L) than the GA + AA group (n = 100, Eos = 0.08 [0.05, 0.13] ×109/L, P = 0.028). No correlation between the genotypes of the other three SNPs and TA patients was observed. Conclusions: Our findings revealed unique genetic pattern in Chinese TA patients that may be partly responsible for the higher risk of TA in this population. FCGR2A/FCGR3A-related immune disorder might contribute to the etiology of TA.

Pigs share many anatomical and physiological features with humans, offering a unique and viable model for biomedical research. Although porcine female germline stem cells (FGSCs) were identified in the juvenile ovary, no reports described the isolation and purification of FGSCs from the pig at sexual maturity. Here, we isolated, purified, and cultured FGSCs from porcine ovaries at sexual maturity. Furthermore, we established and characterized the porcine FGSC (pFGSC) lines. In addition, we found that pFGSC lines could differentiate into oocytes when injection into tissue grafts, including human ovarian tissues. The results show that FGSCs exist in ovaries of Banna mini-pigs at juvenile and sexually maturity. These findings have implications in animal biotechnology applications and regeneration medicine.

Background: The association of metabolic syndrome (MS) with left ventricular (LV) hypertrophy is controversial. The objective of our study was to investigate the influence of MS on LV mass and geometry in community-based hypertensive patients among Han Chinese. Materials and Methods: This study included 1733 metabolic syndrome patients according to the International Diabetes Federation (IDF) definition and 2373 non-MS hypertension patients. LV hypertrophy was diagnosed by the criteria of LV mass ≥49.2 g/m 2.7 for men and 46.7 g/m 2.7 for women. LV geometric patterns (normal, concentric remodeling, concentric or eccentric hypertrophy) were calculated according to LV hypertrophy and relative wall thickness. Logistic regression analysis was used to determine odds ratio (OR) and 95% confidence interval (CI) of MS for LV hypertrophy and LV geometry abnormality. Results: The LV mass and LV mass index were higher in the MS group than in the non-MS group. In multiple adjusted models. LV mass index, LV mass, interventricular septum, and post wall were raised with the increased number of MS disorders. MS was associated with increased LV hypertrophy risk (unadjusted OR 1.38; 95% CI 1.21-1.57); age, sex, and blood pressure (BP; adjusted OR 1.39; 95% CI 1.22-1.59). MS was also associated with increased risk of eccentric hypertrophy in male and female patients. MS was only associated with increased risk of concentric hypertrophy in female patients; and MS was not associated with concentric remodeling. Conclusion: LV mass and LV mass index were associated with the increased number of MS disorders in the Chinese community-based hypertensive population. MS was not only associated with increased LV hypertrophy risk, but also associated with concentric and eccentric LV geometry abnormality, especially in females.

OBJECTIVE:To evaluate the changes in the jaws and the upper airways of unilateral temporomandibular joint ankylosis patients who underwent condylar reconstruction via autogenous coronoid process grafts using cone-beam computed tomography (CBCT). STUDY DESIGN:The 27 included patients underwent CBCT examinations at three stages: T0 (within two weeks before surgery), T1 (two weeks after surgery), and T2 (an average of 13 months after surgery). Forty items related to the maxillofacial hard tissues and the upper airway collected at the three times and the coronoid process graft volumes after surgery were compared. RESULTS:Some integral items related to the mandibular hard tissues exhibited statistical difference shortly after surgery. Some integral items related to maxillofacial hard tissues changing obviously long period after surgery may result from graft remodeling. Asymmetry-related item regarding local neo-condyle and some airway items were significantly different between T0 and T1. Due to variations in graft remodeling, some related local asymmetry items and airway items differed significantly between T0 and T2. CONCLUSIONS:Anteriorly and inferiorly located neo-condyles and a trend toward the pronation of the mandible were observed and the narrowness of the upper airway was improved shortly after surgery. The grafts remodeled differently and some integral and asymmetry items related to neo-condyle changed. The improvements in the upper airway were slightly reduced.

SRCIN1 (SRC kinase signalling inhibitor 1) is a new tumor suppressor gene. Previous studies showed that SRCIN1 played a tumor suppressor role in the development of lung cancer and breast cancer. However, the role of SRCIN1 in osteosarcoma is still unknown. In this study, we demonstrated that SRCIN1 was downregulated in osteosarcoma cell lines compared with osteoblastic cell line. Moreover, SRCIN1 was downregulated in osteosarcoma tissues compared with the adjacent tissues. Further investigation revealed that overexpression of SRCIN1 inhibited the osteosarcoma cell line MG-63 proliferation. This effect was confirmed by measuring the ki-67 and PCNA expression. SRCIN1 overexpression promoted E-cadherin expression and suppressed N-cadherin, Vimentin and Snail expression, suggesting that SRCIN1 overexpression inhibited EMT of the osteosarcoma cell. In addition, ectopic expression of SRCIN1 inhibited the MG-63 cell colony formation and invasion. These data suggested that SRCIN1 acted as a tumor suppressor gene in the development of osteosarcoma.

Source tracing of pathogens is critical for the control and prevention of infectious diseases. Genome sequencing by high throughput technologies is currently feasible and popular, leading to the burst of deciphered bacterial genome sequences. Utilizing the flooding genomic data for source tracing of pathogens in outbreaks is promising, and challenging as well. Here, we employed Yersinia pestis genomes from a plague outbreak at Xinghai county of China in 2009 as an example, to develop a simple two-step strategy for rapid source tracing of the outbreak. The first step was to define the phylogenetic position of the outbreak strains in a whole species tree, and the next step was to provide a detailed relationship across the outbreak strains and their suspected relatives. Through this strategy, we observed that the Xinghai plague outbreak was caused by Y. pestis that circulated in the local plague focus, where the majority of historical plague epidemics in the Qinghai-Tibet Plateau may originate from. The analytical strategy developed here will be of great help in fighting against the outbreaks of emerging infectious diseases, by pinpointing the source of pathogens rapidly with genomic epidemiological data and microbial forensics information.

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by abnormal remodeling of small, peripheral pulmonary arteries. Germline mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene are a major risk factor for developing PAH. At present, the correlation between the BMPR2 mutation and the patient's prognosis remains controversial despite several investigations. In this study, we explored the functional effects of four BMPR2 mutations to dissect the functional significance of the BMPR2 gene defect. Cellular immunofluorescence assay of four mutants (Tyr67Cys, Thr268fs, Ser863Asn, and Gln433X) revealed that the BMPR2 protein containing Thr268fs, Ser863Asn, or Gln433X exhibited abnormal subcellular localization. The BrdU incorporation and TUNEL assay suggested that any of the BMPR2 mutations Thr268fs, Ser863Asn, or Gln433X could improve endothelial cell apoptosis and decrease cell proliferation. All of the four mutants could inhibit nitric oxide (NO) synthesis in HLMVE cells, and ET-1 levels increased in the cells transfected with mutant Ser863Asn. Our results will improve the understanding of the genotype-phenotype correlations and mechanisms associated with BMPR2 mutations.

PURPOSE: Protein kinase plays an essential role in controlling cardiac growth and hypertrophic remodeling. The cardiac troponin I-interacting kinase (TNNI3K), a novel cardiac specific kinase, is associated with cardiomyocyte hypertrophy. However, the precise function of TNNI3K in regulating cardiac remodeling has remained controversial. METHODS AND RESULTS: In a rat model of cardiac hypertrophy generated by transverse aortic constriction, myocardial TNNI3K expression was significantly increased by 1.62 folds (P

Local features in volumetric images have been used to identify correspondences of localized anatomical structures for brain morphometry. However, the correspondences are often sparse thus ineffective in reflecting the underlying structures, making it unreliable to evaluate specific morphological differences. This paper presents a morphometry method (MEACOLP) based on correspondences with improved effectiveness and accuracy. A novel two-level scale-invariant feature transform is used to enhance the detection repeatability of local features and to recall the correspondences that might be missed in previous studies. Template patterns whose correspondences could be commonly identified in each group are constructed to serve as the basis for morphometric analysis. A matching algorithm is developed to reduce the identification errors by comparing neighboring local features and rejecting unreliable matches. The two-sample t-test is finally adopted to analyze specific properties of the template patterns. Experiments are performed on the public OASIS database to clinically analyze brain images of Alzheimer's disease (AD) and normal controls (NC). MEACOLP automatically identifies known morphological differences between AD and NC brains, and characterizes the differences well as the scaling and translation of underlying structures. Most of the significant differences are identified in only a single hemisphere, indicating that AD-related structures are characterized by strong anatomical asymmetry. In addition, classification trials to differentiate AD subjects from NC confirm that the morphological differences are reliably related to the groups of interest.

As an ancient Chinese healing modality which has gained increasing popularity in modern society, acupuncture involves stimulation with fine needles inserted into acupoints. Both traditional literature and clinical data indicated that modulation effects largely depend on specific designated acupoints. However, scientific representations of acupoint specificity remain controversial. In the present study, considering the new findings on the sustained effects of acupuncture and its time-varied temporal characteristics, we employed an electrophysiological imaging modality namely magnetoencephalography with a temporal resolution on the order of milliseconds. Taken into account the differential band-limited signal modulations induced by acupuncture, we sought to explore whether or not stimulation at Stomach Meridian 36 (ST36) and a nearby non-meridian point (NAP) would evoke divergent functional connectivity alterations within delta, theta, alpha, beta and gamma bands. Whole-head scanning was performed on 28 healthy participants during an eyes-closed no-task condition both preceding and following acupuncture. Data analysis involved calculation of band-limited power (BLP) followed by pair-wise BLP correlations. Further averaging was conducted to obtain local and remote connectivity. Statistical analyses revealed the increased connection degree of the left temporal cortex within delta (0.5-4 Hz), beta (13-30 Hz) and gamma (30-48 Hz) bands following verum acupuncture. Moreover, we not only validated the closer linkage of the left temporal cortex with the prefrontal and frontal cortices, but further pinpointed that such patterns were more extensively distributed in the ST36 group in the delta and beta bands compared to the restriction only to the delta band for NAP. Psychophysical results for significant pain threshold elevation further confirmed the analgesic effect of acupuncture at ST36. In conclusion, our findings may provide a new perspective to lend support for the specificity of neural expression underlying acupuncture.

Multiglycosides of Tripterygium wilfordii Hook f (GTW), a Chinese herb-derived medicine used as a remedy for rheumatoid arthritis, are considered to be a reversible anti-fertility drug affecting the mammalian spermatids. However, the mechanism behind this effect is still unknown. To study the possible mechanism behind the impact of GTW on spermatogenesis, we administered 4 groups of 4-week-old male mice with different doses of GTW. We found a dose-dependent decrease in the number of germ cells after 40 days of GTW treatment, and an increase in apoptotic cells from the low-dose to the high-dose group. During this same period the dimethylated level of histone H3 lysine 9 (H3K9me2) in GTW-treated testes germ cells declined. Additionally, spermatogonial stem cells (SSCs) from 6-day-old mice were isolated to evaluate the possible effect of GTW or triptolide on development of SSCs. We found a significantly higher incidence of apoptosis and lower dimethylation level of H3K9me2 in the SSCs of GTW or triptolide treatment than in controls. Thus, these data suggest that the GTW-induced apoptosis might be responsible for the fertility impairment in mice. This damage could be traced back to the early stages of spermatogenesis. GTW also affected the epigenetic modification of H3K9 in spermatogenesis. Molecular dynamics simulation suggested that triptolide and dimethylated or trimethylated H3K9 might have similar interaction mechanisms with EED (embryonic ectoderm development). These candidate activation mechanisms provide the first glimpse into the pathway of GTW-induced gonad toxicity, which is crucial for further research and clinical application.

In our previous study, complete protection was observed in Chinese-origin rhesus macaques immunized with SV1 (20 µg F1 and 10 µg rV270) and SV2 (200 µg F1 and 100 µg rV270) subunit vaccines and with EV76 live attenuated vaccine against subcutaneous challenge with 6×10(6) CFU of Y. pestis. In the present study, we investigated whether the vaccines can effectively protect immunized animals from any pathologic changes using histological and immunohistochemical techniques. In addition, the glomerular basement membranes (GBMs) of the immunized animals and control animals were checked by electron microscopy. The results show no signs of histopathological lesions in the lungs, livers, kidneys, lymph nodes, spleens and hearts of the immunized animals at Day 14 after the challenge, whereas pathological alterations were seen in the corresponding tissues of the control animals. Giemsa staining, ultrastructural examination, and immunohistochemical staining revealed bacteria in some of the organs of the control animals, whereas no bacterium was observed among the immunized animals. Ultrastructural observation revealed that no glomerular immune deposits on the GBM. These observations suggest that the vaccines can effectively protect animals from any pathologic changes and eliminate Y. pestis from the immunized animals. The control animals died from multi-organ lesions specifically caused by the Y. pestis infection. We also found that subcutaneous infection of animals with Y. pestis results in bubonic plague, followed by pneumonic and septicemic plagues. The histopathologic features of plague in rhesus macaques closely resemble those of rodent and human plagues. Thus, Chinese-origin rhesus macaques serve as useful models in studying Y. pestis pathogenesis, host response and the efficacy of new medical countermeasures against plague.

BACKGROUND: DFR (different region) analysis has been developed for typing Yesinia pestis in our previous study, and in this study, we extended this method by using 23 DFRs to investigate 909 Chinese Y. pestis strains for validating DFR-based genotyping method and better understanding adaptive microevolution of Y. pestis. METHODOLOGY/PRINCIPAL FINDINGS: On the basis of PCR and Bionumerics data analysis, 909 Y. pestis strains were genotyped into 32 genomovars according to their DFR profiles. New terms, Major genomovar and Minor genomovar, were coined for illustrating evolutionary relationship between Y. pestis strains from different plague foci and different hosts. In silico DFR profiling of the completed or draft genomes shed lights on the evolutionary scenario of Y. pestis from Y. pseudotuberculosis. Notably, several sequenced Y. pestis strains share the same DFR profiles with Chinese strains, providing data for revealing the global plague foci expansion. CONCLUSIONS/SIGNIFICANCE: Distribution of Y. pestis genomovars is plague focus-specific. Microevolution of biovar Orientalis was deduced according to DFR profiles. DFR analysis turns to be an efficient and inexpensive method to portrait the genome plasticity of Y. pestis based on horizontal gene transfer (HGT). DFR analysis can also be used as a tool in comparative and evolutionary genomic research for other bacteria with similar genome plasticity.