The mutations on the envelope glycoprotein D contribute to the enhanced neurotropism of the pseudorabies virus variant.

The pseudorabies virus (PRV) TJ strain, a variant of PRV, induces more severe neurological symptoms and higher mortality in piglets and mice than the PRV SC strain isolated in 1980. However, the mechanism underlying responsible for the discrepancy in virulence between these strains remains unclear. Our study investigated the differences in neurotropism between PRV TJ and PRV SC using both in vitro and in vivo models. We discovered that PRV TJ enters neural cells more efficiently than PRV SC. Furthermore, we found that PRV TJ has indistinguishable genomic DNA replication capability and axonal retrograde transport dynamics compared to the PRV SC. To gain deeper insights into the mechanisms underlying these differences, we constructed gene-interchanged chimeric virus constructs and assessed the affinity between envelope glycoprotein B, C, and D (gD) and corresponding receptors. Our findings confirmed that mutations in these envelope proteins, particularly gD, significantly contributed to the heightened attachment and penetration capabilities of PRV TJ. Our study revealed the critical importance of the gDΔR278/P279 and gDV338A in facilitating viral invasion. Furthermore, our observations indicated that mutations in envelope proteins have a more significant impact on viral invasion than on virulence in the mouse model. Our findings provide valuable insights into the roles of natural mutations on the PRV envelope glycoproteins in cell tropism, which sheds light on the relationship between cell tropism and clinical symptoms and offers clues about viral evolution.

High-Frequency rTMS Could Improve Impaired Memory in Mild Cognitive Impairment Patients in China: A Randomized Controlled Study.

OBJECTIVE: The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on improving memory deficits in mild cognitive impairment (MCI), as well as to provide visualized evidence for neuronal specificity by using resting-state functional magnetic resonance imaging. MATERIALS AND METHODS: Forty MCI patients were enrolled to receive 10-session and sham-controlled 10Hz-rTMS over the left dorsolateral prefrontal cortex. The resting-state functional magnetic resonance imaging combined with memory scales assessment were performed before and after the intervention. To elucidate the therapeutic mechanism of rTMS, amplitude of low-frequency fluctuations (ALFF) and functional connectivity were calculated. The Pearson correlation was used to measure the relationship between ALFF and memory performance. RESULTS: Compared with the sham group, ALFF significantly increased in the right insula, right inferior frontal gyrus-opercular part, and decreased in the left middle occipital gyrus, left angular gyrus, and left lingual gyrus after rTMS. The change in Auditory Verbal Learning Test scores were negatively correlated with ALFF decreases in the left lingual gyrus. Functional connectivity significantly increased between the posterior cingulate cortex and right supramarginal gyrus, and decreased between the right frontoinsular cortex and right supramarginal gyrus after intervention. CONCLUSION: High-frequency rTMS over the left dorsolateral prefrontal cortex could facilitate improvement on impaired memory in patients with MCI via modulating the neuronal activity and brain network.

Association of body fat and muscle tissue parameters with fatty liver disease identified by ultrasound.

AIMS: To examine the association between body fat and muscle parameters and FLD in individuals of Chinese descent. METHODS: A total of 515 participants who underwent routine check-ups between November 2019 and August 2021 were reviewed. Based on ultrasound performance, the subjects were categorized into the non-FLD group and the FLD group. The prevalence of FLD in sex subgroups was analyzed using logistic regression to calculate the odds ratios (ORs) of body composition parameters with adjustment for confounders. RESULTS: A total of 262 males and 253 females aged 20-84 years were reviewed. In both males and females, higher fat mass index (FMI) (OR: 1.989 for males vs. 1.389 for females), fat mass percent (FM%) (OR: 1.253 for males vs. 1.149 for females), visceral adipose tissue (VAT) (OR: 1.002 for males vs. 1.002 for females), and body mass index (BMI) (OR: 1.530 for males vs. 1.247 for females)were associated with increased ORs of FLD while higher lean mass percent (LM%) (OR: 0.839 for males vs. 0.856 for females)was associated with decreased ORs of FLD. Despite accounting for confounding factors, the associations remained present. Logistic regression of the quartiles of the indices showed associations with the prevalence of FLD. The trends still existed even after adjusting for confounders. CONCLUSION: Independently of age, lipid profiles and other confounders, lower VAT, FM, FMI, FM% and BMI tended to be associated with a lower prevalence of FLD, while lower LM% trended to be associated with a higher prevalence of FLD in both sexes of the general population.

Association of depressive symptoms with retirement in Chinese employees: evidence from national longitudinal surveys from 2011 to 2018.

BACKGROUND: The relationship between depressive symptoms and retirement remains controversial. Thus, we aimed to explore the effect of retirement on individuals' depressive symptoms in Chinese employees. METHODS: In this panel data analysis, a data set from China Health and Retirement Longitudinal Study (CHARLS) in 2011, 2013, 2015 and 2018 was adopted with a total of 1390 employees aged ≥ 45-years-old who had complete follow-up for the four waves. Random-effects logistic regression was used to examine the associations between retirement and depressive symptoms. RESULTS: After adjusting several socio-demographic variables, retirement still increases the risk of depressive symptoms in the retirees (odds ratio 1.5, 95% CI 1.14-1.97). Through subgroup analysis, we found that people who are male, with lower education level, married, living in rural areas, suffering from chronic diseases, and those who do not participate in social activities are more likely to experience depression after retirement. CONCLUSIONS: Retirement can increase the depression risk of Chinese employees. It is necessary to formulate relevant supporting policies to reduce the risk of depression.

Establishment and Validation of Risk Prediction Model for Postpartum Hemorrhage for Pregnant Women ≥35 Years of Age in Natural Delivery.

Context: After the age of 35, women's fertility and physical function gradually decline, and this can significantly increase the risks of postpartum hemorrhage (PPH) after delivery. Sufficient exploration of prenatal indicators of PPH for older pregnant women are still lacking. Objective: The study intended to examine the factors influencing postpartum hemorrhage (PPH) in natural delivery for pregnant women ≥35 years of age and to establish a reliable risk-prediction model. Design: The research team performed a retrospective study. Setting: The study took place at Suzhou Ninth People's Hospital in Suzhou, Jiangsu Province, China. Participants: Participants were 351 pregnant women who had undergone a prenatal examination and vaginal delivery at the hospital between January 2019 and October 2022. Groups: The research team divided participants into two groups: (1) a PPH group, with 52 participants who experienced PPH, and (2) a non-PPH group, with 299 participants who had no PPH. Outcome Measures: The research team: (1) conducted single-factor analysis of the two groups' demographic and clinical characteristics; (2) performed multivariate logistic regression analysis to find the factors influencing PPH; (3) built a risk-prediction model based on the results; and (4) analyzed the model's identification ability, proofreading ability, and clinical applicability using a goodness-of-fit test, a receiver operating characteristic (ROC) curve, a calibration curve, and a decision curve. The team used the SPSS 22.0 and R software for statistical analysis. Results: The incidence of PPH was 14.81%, for the 52 out of 351 participants. The PPH group's age (P < .001), rate of pregnancy-induced hypertension (P = .008), length of the third stage of labor (P = .001), and newborn's birth weight (P < .001) were significantly greater and its FIB before delivery was significantly lower than those of the non-PPH group. The high expression of fibrinogen (FIB) before delivery indicates it may be a protective factor against PPH. The multivariate analysis indicated that a greater age (P = .013), pregnancy-induced hypertension (P = .002), a low FIB level (P < .001), a long third stage of labor (P = .012), and a low birth weight for the newborn (P = .006) were all significantly related to PPH. The research team validated the risk-prediction model, which indicated that the model had good recognition ability (AUC = 0.873). The optimal critical value was 34%, and the sensitivity and specificity were 0.869 and 0.826, respectively. In the comparison of the PPH value that the model predicted and the participants' actual PPH incidence (U = -0.006, Brier = 0.089), the deviation of the model wasn't statistically significant (χ2 = 5.964, P = .651). The analysis of the decision curve found that the net benefits for pregnant women ≥35 years of age were higher than those of the other two extreme curves, showing that the model was clinically effective. Conclusions: The PPH risk-prediction model for vaginal delivery for pregnant women ≥35 years of age showed that a greater age, pregnancy-induced hypertension, a lower prelabor FIB, a longer third stage of labor, and a higher birth weight for the newborn were significantly related to the incidence of PPH and that its use could be clinically helpful.

Effects of medication adherence on disease activity in chronic obstructive pulmonary disease: a systematic review and meta-analysis.

The disease activity of Chronic obstructive pulmonary disease (COPD) patients is often measured, which can could be related to medication adherence. Yet, there is no systematic inventory of studies comparing adherents and non-adherent patients in terms of disease activity. The systematic review and meta-analysis aimed to reveal the effect of medication adherence on disease activity in patients with COPD. For the present meta-analysis, studies comparing medication adherence in adherents and non-adherent patients were screened and included. Results were expressed as mean difference (MD) and 95% CI. A total of eleven identified studies matched the inclusion criteria, reporting on a total of 6,346 COPD patients in the analysis. The number of exacerbations in COPD patients over a year was significantly lower in non-adherent patients than in adherent subjects (MD = 0.69, 95% CI [0.36,1.01], P < 0.0001). Similarly, a significant difference was observed between medication-adherent and non-adherent groups in FEV1 (MD = -166.47, 95% CI [-255.03, -77.92], P= 0.0002). Interestingly, the results of the meta-analysis showed no significant difference between medication-adherent and non-adherent patients in SGRQ (MD = -0.85, 95% CI [-4.98, 3.27], P= 0.68), CAT (MD = -0.83, 95% CI [-1.78, 0.13], P= 0.09), and FEV1% (MD = -3.33, 95% CI [-6.83, 0.17], P= 0.06).The studies performed suggested that clinical medical staff should pay attention to the medication behavior of COPD patients and effectively improve the medication adherence of patients.

TgMORN2, a MORN Family Protein Involved in the Regulation of Endoplasmic Reticulum Stress in Toxoplasma gondii.

MORN proteins play a key role in the cytoskeletal structure of eukaryotes and are essential for the close arrangement of the endoplasmic reticulum and plasma membrane. A gene with nine MORN motifs (TGGT1_292120, named TgMORN2) was identified in the Toxoplasma gondii genome; it was presumed to belong to the MORN protein family and to have the function of forming the cytoskeleton, which affects the survival of T. gondii. However, the genetic deletion of MORN2 did not noticeably affect parasite growth and virulence. Using adjacent protein labeling techniques, we identified a network of TgMORN2 interactions, which mainly included endoplasmic reticulum stress (ER stress)-related proteins. In exploring these data, we found that the pathogenicity of the KO-TgMORN2 strain was significantly reduced in the case of tunicamycin-induced ER stress. Reticulon TgRTN (TGGT1_226430) and tubulin ß-Tubulin were identified as interaction proteins of TgMORN2. Collectively, TgMORN2 plays a role in ER stress, which lays a foundation for further research on the function of the MORN protein in T. gondii.

Feline Calicivirus Proteinase-Polymerase Protein Degrades mRNAs To Inhibit Host Gene Expression.

To replicate efficiently and evade the antiviral immune response of the host, some viruses degrade host mRNA to induce host gene shutoff via encoding shutoff factors. In this study, we found that feline calicivirus (FCV) infection promotes the degradation of endogenous and exogenous mRNAs and induces host gene shutoff, which results in global inhibition of host protein synthesis. Screening assays revealed that proteinase-polymerase (PP) is a most effective factor in reducing mRNA expression. Moreover, PP from differently virulent strains of FCV could induce mRNA degradation. Further, we found that the key sites of the PP protein required for its proteinase activity are also essential for its shutoff activity but also required for viral replication. The mechanism analysis showed that PP mainly targets Pol II-transcribed RNA in a ribosome-, 5' cap-, and 3' poly(A) tail-independent manner. Moreover, purified glutathione S-transferase (GST)-PP fusion protein exhibits RNase activity in vitro in assays using green fluorescent protein (GFP) RNA transcribed in vitro as a substrate in the absence of other viral or cellular proteins. Finally, PP-induced shutoff requires host Xrn1 to complete further RNA degradation. This study provides a newly discovered strategy in which FCV PP protein induces host gene shutoff by promoting the degradation of host mRNAs. IMPORTANCE Virus infection-induced shutoff is the result of targeted or global manipulation of cellular gene expression and leads to efficient viral replication and immune evasion. FCV is a highly contagious pathogen that persistently infects cats. It is unknown how FCV blocks the host immune response and persistently exists in cats. In this study, we found that FCV infection promotes the degradation of host mRNAs and induces host gene shutoff via a common strategy. Further, PP protein for different FCV strains is a key factor that enhances mRNA degradation. An in vitro assay showed that the GST-PP fusion protein possesses RNase activity in the absence of other viral or cellular proteins. This study demonstrates that FCV induces host gene shutoff by promoting the degradation of host mRNAs, thereby introducing a potential mechanism by which FCV infection inhibits the immune response.

Immunophenotype in acute exacerbation of chronic obstructive pulmonary disease: a cross-sectional study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease, and the immune inflammatory response is thought to play an important role in pathogenesis. However, the immunophenotype of patients with COPD is unknown. Herein, we evaluated the immunophenotype of patients with acute exacerbation of COPD (AECOPD). METHODS: A cross-sectional study was conducted in West China Hospital from September 2018 to October 2019. The proportion of CD4 + T lymphocyte subtypes (Th1, Th2, Th17 and Treg) and levels of serum cytokines in the peripheral blood of patients with AECOPD, stable COPD (SCOPD), healthy smokers (HSs)and healthy controls (HCs) were evaluated. RESULTS: A total of 15 HCs, 19 HSs, 42 patients with SCOPD, and 55 patients with AECOPD were included. Compared to patients with SCOPD, Th1 cells, Th17 cells, Treg cell ratio, Th1/Th2 cell ratio, and the levels of C-reactive protein, interleukin (IL)-6, and IL-10 were significantly increased in patients with AECOPD (P < 0.001), while the proportion of Th2 cells was significantly reduced (P < 0.01). The proportion of Th17 cells was positively correlated with COPD Assessment Test score (r = 0.266, P = 0.009), modified Medical Research Council dyspnea score (r = 0.858, P < 0.0001), and Th1 cell ratio (r = 0.403, P < 0.0001) and negatively correlated with forced vital capacity (r = - 0.367, P = 0.009) and proportion of Th2 cells (r = - 0.655, P < 0.0001). CONCLUSIONS: The immunophenotype of patients with AECOPD shows abnormal activation of Th1, Th17, and Treg cells. There is a correlation between the proportion of Th17 cells and the severity of COPD; therefore, this may represent a novel index for the evaluation of COPD severity. TRIAL REGISTRATION: China Clinical Trials Registry, ChiCTR1800018452, registered 19 September 2018, https://www.chictr.org.cn/index.aspx .

Efficacy of targeted therapy in patients with HER2-positive non-small cell lung cancer: A systematic review and meta-analysis.

Anti-human epidermal growth factor receptor 2 (HER2) therapy is an effective treatment for HER2-positive gastric and breast malignancies. However, the efficacy of HER2-targeted therapy in non-small cell lung cancer (NSCLC) patients with HER2 alterations remains controversial. We searched studies on HER2-targeted therapy in NSCLC patients that reported objective response rate (ORR), disease control rate (DCR) and progressionfree survival (PFS) published from database inception to 30 May 2021. A total of 32 trials involving 958 patients were included. The ORRs of HER2-TKIs targeted therapy, humanised monoclonal antibody, trastuzumab-based treatment and antibody-drug conjugate (ADC) (T-DM1) were 22% (95% CI 11-31), 23% (95% CI 20-65), 26% (95% CI 14-39) and 16% (95% CI _6-37), while that of ADC (DS-8201) was 60% (95% CI 35-85). The DCRs of these groups were 59% (95% CI 49-69), 39% (95% CI _9-88), 63% (95% CI 37-89), 31% (95% CI 4-58) and 87% (95% CI 62-112), respectively. In the subgroup analysis, numerically higher ORRs and DCRs were observed in the poziotinib (38%; 75%) and pyrotinib (35%; 83%) groups. The median PFSs of these groups were 5.51 months, 3.09 months, 4.61 months, 2.65 months and 12.04 months, respectively. HER2-targeted therapy can be considered an acceptable treatment strategy for NSCLC patients with HER2 alterations. In particular, ADC (DS-8201), pyrotinib and poziotinib demonstrated promising anti-tumour activity in HER2-positive NSCLC.

Effects of dietary mannan oligosaccharides (MOS) supplementation on metabolism, inflammatory response and gut microbiota of juvenile Nile tilapia (Oreochromis niloticus) fed with high carbohydrate diet.

High-carbohydrate diet could achieve cost-sparing effect in aquafeed, but it may cause adverse effects on the growth condition or health status of fish. In order to reduce the adverse effects caused by high carbohydrate diet, mannan oligosaccharides (MOS), a commonly used prebiotics, was used as the feed additive to feed juvenile Nile tilapia (Oreochromis niloticus) (1.19 ± 0.01g) for ten weeks. Three treatments including CON (35% carbohydrate diet), HC (45% carbohydrate diet) and HM (45% carbohydrate supplemented diet with 5 g/kg MOS) were involved. The results showed that MOS supplementation increased the weight gain and body length of juvenile Nile tilapia compared with the HC group. Addition of MOS decreased serum glucose and liver glycogen by increasing enzymes activity related to glycolysis. Furthermore, supplementation of MOS decreased the high carbohydrate diet induced triglycerides accumulation in liver by reducing the expression level of genes related to TG synthesis. Dietary MOS also down-regulated the gene expression level of inflammation factors in liver. Intestinal bacterial composition analyses showed that supplementation of MOS in high carbohydrate diet altered the gut microbial composition and enriched pathways related to the glucose metabolism based on KEGG analyses. In general, our results demonstrated that MOS supplementation in high carbohydrate diet could regulate glucose and lipid homeostasis which may be related to the alteration of gut microbiota. These findings shed light on the application of prebiotics to increase the growth performance, alleviate the metabolic disorders and regulate inflammatory response in aquaculture.

Bacillus amyloliquefaciens protects Nile tilapia against Aeromonas hydrophila infection and alleviates liver inflammation induced by high-carbohydrate diet.

Carbohydrates are widely distributed in nature as an important nutritional substance and energy source. However, the utilization efficiency of carbohydrates is very poor in fish. Over consumption of carbohydrates will cause excessive inflammatory response and result in lower pathogen resistance in fish. Probiotics have been widely used to prevent inflammation, but the underlying mechanism still needs more exploration. In this study, three diets, including a control diet (CD), a high-carbohydrate diet (HD) and the HD supplemented with Bacillus amyloliquefaciens SS1 (HDB) were used to feed Nile tilapia for 10 weeks. At the end of the feeding trial, fish were challenged with Aeromonas hydrophila (A. hydrophila) for 7 days. The data showed that the addition of Bacillus amyloliquefaciens SS1 (B. amyloliquefaciens SS1) significantly increased the survival rate and enhanced the respiratory burst activity of head kidney leukocytes in Nile tilapia. B. amyloliquefaciens SS1 treatment significantly elevated the anti-oxidative capability, which was evidenced by higher activities of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC), and higher content of reduced glutathione (GSH) in the serum. Administration with B. amyloliquefaciens SS1 effectively suppressed inflammatory response in the liver by inhibiting nuclear factor kappa-B (NF-κB)/interleukin-1 beta (IL-1ß) inflammatory signaling pathway. In vitro analysis suggested that intestinal bacteria derived-acetate has the antioxidant capability, which may account for the alleviation of inflammation. Overall, this study demonstrated that dietary supplementation with B. amyloliquefaciens SS1 protected Nile Tilapia against A. hydrophila infection and suppressed liver inflammation by enhancing antioxidant capability.

Equations for predicting DXA-measured visceral adipose tissue mass based on BMI or weight in adults.

BACKGROUND: Obesity, especially presenting with excessive amounts of visceral adipose tissue (VAT), is strongly associated with insulin resistance (IR), atherosclerosis, metabolic syndrome, and cardiovascular diseases (CVDs). AIMS: To construct a predication equation for estimating VAT mass using anthropometric parameters and validate the models with a validation group. METHODS: Five hundred fifteen subjects (366 for the derivation group and 149 for the validation group) were enrolled in the study. The anthropometric parameters, blood lipid profile, and VAT mass were accessed from medical records. Stepwise regression was applied to develop prediction models based on the dual X-ray absorptiometry (DXA)-measured VAT mass in the derivation group. Bland-Altman plots and correlation analysis were performed to validate the agreements in the validation group. The performance of the prediction equations was evaluated with the Hosmer-Lemeshow test and area under the curve (AUC). RESULTS: Model 1, which included age, sex, body mass index (BMI), triglyceride (TG), high-density lipoprotein (HDL), and the grade of hepatic steatosis, had a variance of 70%, and model 2, which included age, sex, weight, height, TG, HDL, and the grade of hepatic steatosis, had a variance of 74%. The VAT mass measured by DXA was correlated with age, sex, height, weight, BMI, TG, HDL, and grade of hepatic steatosis. In the validation group, the VAT mass calculated by the prediction equations was strongly correlated with the DXA-VAT mass (r = 0.870, r = 0.875, respectively). The AUC, sensitivity, and specificity of the two prediction equations were not significantly different (both P = 0.933). CONCLUSION: The study suggests that prediction equations including age, sex, height, BMI, weight, TG, HDL, and the grade of hepatic steatosis could be useful tools for predicting VAT mass when DXA is not available.

Effects of the Otago Exercise Program in older hypertensive patients with pre-frailty.

[Purpose] We aimed to investigate the effects of the Otago Exercise Program in older hypertensive patients with pre-frailty. [Participants and Methods] Participants were randomly divided into the (Otago Exercise Program OEP) group (n=37) and the control group (n=38). The OEP group completed the exercise step 3 times during hospitalization. For 12 weeks, the OEP group exercised at home and the control group completed daily walking activities ≥3 times per week. [Results] There were significant differences in FRAIL scale score, 10-meter gait speed, one-leg standing test results, and functional reach test results between the two groups. In addition to the above indicators, the differences in diastolic blood pressure were also statistically significant between the two groups before and after intervention. [Conclusion] The OEP can improve frailty and the ability to perform activity in older hypertensive patients with pre-frailty. Diastolic blood pressure decreases significantly after intervention.

GmFULa improves soybean yield by enhancing carbon assimilation without altering flowering time or maturity.

KEY MESSAGE: GmFULa improved soybean yield by enhancing carbon assimilation. Meanwhile, different from known yield-related genes, it did not alter flowering time or maturity. Soybean (Glycine max (L.) Merr.) is highly demanded by a continuously growing human population. However, increasing soybean yield is a major challenge. FRUITFULL (FUL), a MADS-box transcription factor, plays important roles in multiple developmental processes, especially fruit and pod development, which are crucial for soybean yield formation. However, the functions of its homologs in soybean are not clear. Here, through haplotype analysis, we found that one haplotype of the soybean homolog GmFULa (GmFULa-H02) is dominant in cultivated soybeans, suggesting that GmFULa-H02 was highly selected during domestication and varietal improvement of soybean. Interestingly, transgenic overexpression of GmFULa enhanced vegetative growth with more biomass accumulated and ultimately increased the yield but without affecting the plant height or changing the flowering time and maturity, indicating that it enhances the efficiency of dry matter accumulation. It also promoted the yield factors like branch number, pod number and 100-seed weight, which ultimately increased the yield. It increased the palisade tissue cell number and the chlorophyll content to promote photosynthesis and increase the soluble sugar content in leaves and fresh seeds. Furthermore, GmFULa were found to be sublocalized in the nucleus and positively regulate sucrose synthases (SUSs) and sucrose transporters (SUTs) by binding with the conserved CArG boxes in their promoters. Overall, these results showed GmFULa promotes the capacity of assimilation and the transport of the resultant assimilates to increase yield, and provided insights into the link between GmFULa and sucrose synthesis with transport-related molecular pathways that control seed yield.

Transcriptional mechanism of differential sugar accumulation in pulp of two contrasting mango (Mangifera indica L.) cultivars.

Temporal transcriptome analysis combined with targeted metabolomics was employed to investigate the mechanisms of high sugar accumulation in fruit pulp of two contrasting mango cultivars. Ten sugar metabolites were identified in mango pulp with the most dominant being d-glucose. Analysis of the gene expression patterns revealed that the high-sugar cultivar prioritized the conversion of sucrose to d-glucose by up-regulating invertases and ß-glucosidases and increased other genes directly contributing to the synthesis of sucrose and d-glucose. In contrast, it repressed the expression of genes converting sucrose, d-glucose and other sugars into intermediates compounds for downstream processes. It also strongly increased the expression of alpha-amylases which may promote high degradation of starch into d-glucose. Besides, ¾ of the sugar transporters was strongly up-regulated, indicative of their preponderant role in sugar accumulation in mango fruit. Overall, this study provides a good insight into the regulation pattern of high sugar accumulation in mango pulp.

Oncogenic microRNA-765 promotes the growth and metastasis of breast carcinoma by directly targeting ING4.

Previous investigations have proved that microRNA (miR)-765 is significantly overexpressed in multiple tumor types. Nevertheless, the underlying molecular mechanism of miR-765 in mediating breast carcinoma cell growth and metastasis remains unclear. Quantitative real-time polymerase chain reaction was used to determine the levels of miR-765 and inhibitor of growth 4 (ING4) in breast carcinoma tissues and breast carcinoma cells. Cell proliferation, colony formation, wound healing, and Transwell invasion assays were used to analysis the role of miR-765 on breast carcinoma cell growth and aggressiveness. The expressions of ING4 were determined using Western blot analysis and immunohistochemical staining. The direct target of ING4 and miR-765 was confirmed using the luciferase reporter assay. Nude mice were subcutaneously implanted with miR-765 inhibitor transfected MDA-MB-231 cells to determine the potential role of miR-765 in tumor growth in vivo. We observed that miR-765 is overexpressed in breast carcinoma tissue and breast cancer cells. By using luciferase reporter gene bioassay, we find that ING4 is the direct target of miR-765 in breast carcinoma. The level of ING4 is inversely associated with the level of miR-765. The gain-of-function and loss-of-function experiments in vitro indicate that the downregulation of miR-765 suppresses the growth, mobility, and invasion abilities of breast cancer cells by inhibiting ING4. In addition, overexpression of ING4 suppresses the aggressiveness of the MDA-BA-231 cell that is induced by miR-761 in vitro. In this study, we prove that miR-765 regulates the growth and metastasis of breast cancer via modulating miR-765-ING4-negative feedback loop.

[Promoting tanshinone synthesis of Salvia miltiorrhiza root by a seed endophytic fungus, Phoma herbarum D603].

The interaction of endophytes and host plant is an effective mean to regulate the growth and secondary metabolism of medicinal plants. Here we want to elucidate the effects and mechanism of Phoma herbarum D603 on the root development and tanshinone synthesis in root of Salvia miltiorrhiza by endophyte-plant coculture system. The mycelium of P. herbarum D603 was colonized in the root tissue space, and formed a stable symbiotic relationship with host plant. The in vitro activities analysis showed that the concentration of IAA produced by D603 can reach(6.45±0.23) µg·mL~(-1), and this strain had some abilities of phosphorus solubilization and siderophore production activities. The coculture experiment showed that strain D603 can significantly promote the synthesis and accumulation of tanshinones in the root of S. miltiorrhiza, in which after 8 weeks of treatment with D603, the content of tanshinone Ⅱ_A in the roots reached up to(1.42±0.59) mg·g~(-1). By the qRT-PCR analysis results, we found that D603 could improve the expression levels of some key genes(DXR, DXS, GGPP, HMGR, CPS) of tanshinone biosynthesis pathway in host plant S. miltiorrhiza, but the promoting effect mainly occurred in the early stage of the interaction, and the enzyme activity level decreased in varying degrees of the later stage. In summary, seed-associated endophyte P. herbarum D603 can promote the growth and root development of S. miltiorrhiza by producing hormones, promoting nutrient absorption and siderophore production, and promote the synthesis and accumulation of tanshinones by regulating the expression level of key genes in the synthetic pathway in S. miltiorrhiza.

Efficacy and safety of dupilumab for the treatment of uncontrolled asthma: a meta-analysis of randomized clinical trials.

BACKGROUND: Several recent clinical trials have assessed the effects of dupilumab in uncontrolled asthma, but reached no definite conclusion. We therefore conducted this meta-analysis to evaluate the overall efficacy and safety of dupilumab for the treatment of uncontrolled asthma. METHODS: All randomized controlled trials were included. Standard mean differences (SMD) or relative risks (RR) were calculated using Fixed-or random-effects models. RESULTS: Five studies involving 3369 patients were identified. Pooled analysis showed significant improvements in the first-second forced expiratory volume (FEV1) (SMD = 4.29, 95% CI: 2.78-5.81) and Asthma Quality of Life Questionnaire scores (SMD = 4.39, 95% CI: 1.44-7.34). Dupilumab treatments were also associated with significantly decreased 5-item Asthma Control Questionnaire scores (SMD = - 4.95, 95% CI: - 7.30 to - 2.60), AM and PM asthma symptom scores (SMD = - 5.09, 95% CI: - 6.40 to - 3.77; SMD = - 4.92, 95% CI: - 5.98 to - 3.86, respectively), and severe exacerbation risk (RR = 0.73; 95% CI: 0.67-0.79) compared with placebo, with similar incidence of adverse events (RR = 1.0; 95% CI: 0.96-1.04). CONCLUSION: Dupilumab treatment is relatively well-tolerated and could significantly improve FEV1, symptoms, asthma control, and quality of life, and reduced severe exacerbation risk in patients with uncontrolled asthma.

ATP-binding cassette sub-family a member1 gene mutation improves lipid metabolic abnormalities in diabetes mellitus.

BACKGROUND: Patients with diabetes mellitus were often accompanied with hyperlipidemia. ATP-binding cassette sub-family A member1 (ABCA1) promotes the efflux of lipids and thereby mediates the metabolism of cholesterol. The aim of our study was to determine the associations of ABCA1 gene polymorphisms with the risks of diabetes mellitus and dyslipidemia in diabetic patients. METHODS: We retrieved literature about the relationship between ABCA1 gene polymorphisms (C69T and R230C) and the risk of diabetes through PubMed, Web of Science, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Cochrane database. Weighted mean difference (WMD) and odds ratio (OR) were used to compare continuous and dichotomous variables, respectively, accompanied by their 95% confidence interval (CI). RESULTS: A total of 1746 diabetic patients and 1292 non-diabetic controls were enrolled. All subjects were Caucasians. ABCA1 R230C T allele was significantly associated with reduced the risk of diabetes (OR = 0.75, 95% CI = 0.57-0.98, P = 0.04). There was no association of ABCA1 C69T gene polymorphisms with the risk of diabetes. However, subgroup analyses showed that the ABCA1 C69T gene mutation significantly reduced the risk of hypertriglyceridemia in diabetic patients as compared with that in non-diabetic subjects (dominant model: WMD =0.66, 95% CI = 0.52-0.8, P < 0.0001; recessive model: WMD = 0.47, 95%CI = 0.11-0.83, P = 0.01). CONCLUSIONS: ABCA1 R230C T allele gene mutation is a protective in decreasing the risk of diabetes in Caucasians and ABCA1 C69T gene mutation markedly influences the level of lipid metabolism in diabetic patients.