Forces driving transposable element load variation during Arabidopsis range expansion.

Genetic load refers to the accumulated and potentially life-threatening deleterious mutations in populations. Understanding the mechanisms underlying genetic load variation of transposable element (TE) insertion, a major large-effect mutation, during range expansion is an intriguing question in biology. Here, we used 1,115 global natural accessions of Arabidopsis (Arabidopsis thaliana) to study the driving forces of TE load variation during its range expansion. TE load increased with range expansion, especially in the recently established Yangtze River basin population. Effective population size, which explains 62.0% of the variance in TE load, high transposition rate, and selective sweeps contributed to TE accumulation in the expanded populations. We genetically mapped and identified multiple candidate causal genes and TEs, and revealed the genetic architecture of TE load variation. Overall, this study reveals the variation in TE genetic load during Arabidopsis expansion and highlights the causes of TE load variation from the perspectives of both population genetics and quantitative genetics.

Pembrolizumab and Enzalutamide in Patients with Abiraterone Acetate-Pretreated Metastatic Castration-Resistant Prostate Cancer: Cohort C of the Phase 1b/2 KEYNOTE-365 Study.

BACKGROUND: Limited responses have been observed in patients treated with enzalutamide after disease progression on abiraterone for metastatic castration-resistant prostate cancer (mCRPC), but androgen receptor signaling impacts T-cell function. OBJECTIVE: To evaluate the efficacy and safety of pembrolizumab plus enzalutamide in mCRPC. DESIGN, SETTING, AND PARTICIPANTS: Patients in cohort C of the phase 1b/2 KEYNOTE-365 study, who received ≥4 wk of treatment with abiraterone acetate in the prechemotherapy mCRPC state and experienced treatment failure or became drug-intolerant, were included. INTERVENTION: Pembrolizumab 200 mg intravenously every 3 wk plus enzalutamide 160 mg orally once daily. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were safety, the confirmed prostate-specific antigen (PSA) response rate, and the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 on blinded independent central review (BICR). Secondary endpoints included radiographic progression-free survival (rPFS) on BICR and overall survival (OS). RESULTS AND LIMITATIONS: A total of 102 patients received pembrolizumab plus enzalutamide. Median follow-up was 51 mo (interquartile range 37-56). The confirmed PSA response rate was 24% (95% confidence interval [CI] 16-33%). The confirmed ORR was 11% (95% CI 2.9-25%; 4/38 patients; two complete responses). Median rPFS was 6.0 mo (95% CI 4.1-6.3). Median OS was 20 mo (95% CI 17-24). Treatment-related adverse events (TRAEs) occurred in 94 patients (92%); grade 3-5 TRAEs occurred in 44 patients (43%). The incidence of treatment-related rash was higher with combination therapy than expected from the safety profile of each drug. One patient (1.0%) died of a TRAE (cause unknown). Study limitations include the single-arm design. CONCLUSIONS: Pembrolizumab plus enzalutamide had limited antitumor activity in patients who received prior abiraterone treatment without previous chemotherapy for mCRPC, with a safety profile consistent with the individual profiles of each agent. PATIENT SUMMARY: Pembrolizumab plus enzalutamide showed limited antitumor activity and manageable safety in patients with metastatic castration-resistant prostate cancer. The KEYNOTE-365 trial is registered on ClinicalTrials.gov as NCT02861573.

Pembrolizumab Plus Chemotherapy Followed by Pembrolizumab in Patients With Early Triple-Negative Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: In the phase 3 KEYNOTE-522 study, addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab significantly increased pathologic complete response (pCR) and event-free survival (EFS) vs neoadjuvant chemotherapy in patients with early triple-negative breast cancer. Objective: To evaluate efficacy and safety outcomes for patients enrolled in East/Southeast Asia (Asia) in KEYNOTE-522. Design, Setting, and Participants: KEYNOTE-522, a multicenter, double-blind, randomized clinical trial, enrolled 1174 patients between March 7, 2017, and September 13, 2018. For interim EFS and overall survival (OS) analyses (data cutoff, March 23, 2021), median follow-up was 39.8 months (range, 30.4-46.9 months) for pembrolizumab plus chemotherapy and 40.8 months (range, 30.1-46.9 months) for placebo plus chemotherapy. Data cutoff for pCR analysis was September 24, 2018. This secondary analysis included adults enrolled in Asia with newly diagnosed, previously untreated, nonmetastatic triple-negative breast cancer (tumor stage T1c and nodal stage N1-2 or tumor stage T2-4 and nodal stage N0-2) and Eastern Cooperative Oncology Group performance status of 0 to 1, regardless of programmed cell death ligand 1 (PD-L1) status. Intervention: Patients were randomized 2:1 to 4 cycles of pembrolizumab (200 mg every 3 weeks) or placebo plus carboplatin and paclitaxel and another 4 cycles of pembrolizumab or placebo plus doxorubicin or epirubicin and cyclophosphamide before surgery. After definitive surgery, patients received pembrolizumab or placebo every 3 weeks for 9 cycles or until recurrence or unacceptable toxic effects. Main Outcomes and Measures: The main outcome was pCR (no evidence of primary tumor after neoadjuvant therapy or carcinoma in situ after neoadjuvant therapy and no regional lymph node involvement after neoadjuvant therapy) at the time of definitive surgery and EFS. Results: A total of 216 of 1174 randomized patients (all female; median [range] age, 46.0 [24.0-71.0] years) were from Korea, Japan, Taiwan, and Singapore (136 in the pembrolizumab plus chemotherapy group and 80 in the placebo plus chemotherapy group). Of these patients, 104 (76.5%) in the pembrolizumab plus chemotherapy group and 60 (75.0%) in the placebo plus chemotherapy group had a tumor PD-L1 combined positive score of 1 or greater. Pathologic complete response was 58.7% (95% CI, 46.7%-69.9%) with pembrolizumab plus chemotherapy and 40.0% (95% CI, 26.4%-54.8%) with placebo plus chemotherapy; benefit was observed regardless of PD-L1 status. Thirteen patients (9.6%) in the pembrolizumab plus chemotherapy group and 20 patients (25.0%) in the placebo plus chemotherapy group had EFS events (hazard ratio, 0.35; 95% CI, 0.17-0.71). The 36-month EFS rate was 91.2% (95% CI, 85.0%-94.9%) with pembrolizumab plus chemotherapy and 77.2% (95% CI, 66.3%-85.0%) with placebo plus chemotherapy. Grade 3 to 4 treatment-related adverse events occurred in 109 patients (80.1%) receiving pembrolizumab plus chemotherapy and 64 patients (81.0%) receiving placebo plus chemotherapy. Conclusions and Relevance: In this subgroup analysis of patients enrolled in Asia in KEYNOTE-522, neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab led to clinically meaningful improvements in pCR and EFS vs neoadjuvant chemotherapy alone. These findings support the use of neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab as a standard-of-care therapy for patients in Asian countries with early triple-negative breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03036488.

Cyclin-dependent kinase 5 negatively regulates antiviral immune response by disrupting myeloid differentiation primary response protein 88 self-association.

As a member of the pattern recognition receptors (PRRs) involving in the innate immune system, Toll-like receptors (TLRs) can sense a wide range of microbial pathogens and combat infections by producing antimicrobial products, inflammatory cytokines, and chemokines. All TLRs, with the exception of TLR3, activate a signalling cascade via the myeloid differentiation primary response gene 88 (MyD88). Therefore, the activation of MyD88-dependent signalling pathway must be finely controlled. Herein, we identified that cyclin-dependent kinase 5 (CDK5) negatively regulated TLR-MyD88 signalling pathway by targeting MyD88. Overexpression of CDK5 reduced the production of interferons (IFNs), while a deficiency in CDK5 increased the expression of IFNs in response to vesicular stomatitis virus (VSV) infection. Mechanistically, CDK5 suppressed the formation of MyD88 homodimers, resulting in the attenuated production of IFNs induced by VSV infection. Surprisingly, its kinase activity does not play a role in this process. Therefore, CDK5 can act as an internal regulator to prevent excessive production of IFNs by restricting TLR-MyD88-induced activation of antiviral innate immunity in A549 cells.

c-MYC mediates the crosstalk between breast cancer cells and tumor microenvironment.

The MYC oncogenic family is dysregulated in diverse tumors which is generally linked to the poor prognosis of tumors. The members in MYC family are transcription factors which are responsible for the regulation of various genes expression. Among them, c-MYC is closely related to the progression of tumors. Furthermore, c-MYC aberrations is tightly associated with the prevalence of breast cancer. Tumor microenvironment (TME) is composed of many different types of cellular and non-cellular factors, mainly including cancer-associated fibroblasts, tumor-associated macrophages, vascular endothelial cells, myeloid-derived suppressor cells and immune cells, all of which can affect the diagnosis, prognosis, and therapeutic efficacy of breast cancer. Importantly, the biological processes occurred in TME, such as angiogenesis, immune evasion, invasion, migration, and the recruition of stromal and tumor-infiltrating cells are under the modulation of c-MYC. These findings indicated that c-MYC serves as a critical regulator of TME. Here, we aimed to summarize and review the relevant research, thus to clarify c-MYC is a key mediator between breast cancer cells and TME. Video Abstract.

Pembrolizumab plus Olaparib in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort A Study.

BACKGROUND: Pembrolizumab and olaparib have shown single-agent activity in patients with previously treated metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: To evaluate the efficacy and safety of pembrolizumab plus olaparib in mCRPC. DESIGN, SETTING, AND PARTICIPANTS: Cohort A of the phase 1b/2 KEYNOTE-365 study enrolled patients with molecularly unselected, docetaxel-pretreated mCRPC whose disease progressed within 6 mo of screening. INTERVENTION: Pembrolizumab 200 mg intravenously every 3 wk plus olaparib 400-mg capsule or 300-mg tablet orally twice daily. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were safety, confirmed prostate-specific antigen (PSA) response rate, and objective response rate (ORR) as per Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, by blinded independent central review. The secondary endpoints included radiographic progression-free survival (rPFS) and overall survival (OS). RESULTS AND LIMITATIONS: Of 104 enrolled patients, 102 were treated. The median age was 70 yr (interquartile range [IQR], 65-76), and 59 patients (58%) had measurable disease as per RECIST v1.1. The median time from the first dose to database cutoff was 24 mo (IQR, 22-47). The confirmed PSA response rate was 15%. The confirmed ORR was 8.5% (five partial responses) for patients with measurable disease. The median rPFS was 4.5 mo (95% confidence interval [CI], 4.0-6.5) and median OS was 14 mo (95% CI, 10.4-18.2). Clinical activity was consistent across the programmed death ligand 1 (PD-L1)-positive and homologous recombination repair mutation subgroups. Treatment-related adverse events (TRAEs) occurred in 93 patients (91%). Grade 3-5 TRAEs occurred in 49 patients (48%). Six deaths (5.9%) were due to adverse events; two (myocardial infarction and unknown cause) were attributed to treatment. Limitations of the study include the single-arm design. CONCLUSIONS: Pembrolizumab plus olaparib had a safety profile consistent with the profiles of the individual agents and demonstrated antitumor activity in previously treated patients with molecularly unselected, docetaxel-pretreated mCRPC. PATIENT SUMMARY: Pembrolizumab plus olaparib showed antitumor activity and expected safety in patients with metastatic castration-resistant prostate cancer.

Mycoplasma pneumoniae infection and recurrent respiratory tract infection in children / 公共卫生与预防医学

Objective To analyze the risk factors of mycoplasma pneumoniae (MP) infection and recurrent respiratory tract infection (RRTI) in children, and to provide reference for early clinical intervention. Methods A total of 648 RRTI children admitted to our hospital from October 2018 to December 2020 were selected. Serum MP antibody levels were detected by semi-quantitative method. According to whether the children were combined with mycoplasma infection, they were divided into experimental group (MP positive, n=283) and control group (MP negative, n=365). Age, gender, body mass index, nutrient deficiency, preterm birth, anemia, onset season, collective living, antibiotics application were collected from the two groups. Logistic regression was used to analyze the independent risk factors of MP infection in RRTI children. Results Among of 648 RRTI children, 283 (43.67%) had MP infection. There was no statistical significance in MP infection of pneumonia in children of different ages and genders between the two groups (P>0.05).There were statistically significant differences between the two groups in nutrient deficiency, onset season, length of hospital stay, days of fever, group living, application of antibiotics and invasive operation (P<0.05). Logistic regression analysis showed that the onset season, length of hospital stay, group living were independent risk factors for MP infection in RRTI children (P<0.05). Conclusion The risk of MP infection in RRTI children is higher, and the main risk factors are onset season, length of hospital stay, group living and application of antibiotics.

Effects of hydrolysable tannins from Terminalia citrina on type III secretion system (T3SS) and their intestinal metabolite urolithin B represses Salmonella T3SS through Hha-H-NS-HilD-HilC-RtsA-HilA regulatory pathway.

Gamma-proteobacteria is a class of gram-negative opportunistic pathogens existing in the intestinal flora, often leading to diarrhea and intestinal infectious diseases, and plays an important role in maintaining intestinal homeostasis. Type III secretion system (T3SS), an important virulence system, is closely related to the adhesion and invasion and pathogenicity to host cells. Therefore, anti-virulence agents targeting T3SS are important strategies for controlling pathogenic infections. In this study, the anti-Salmonella T3SS active compounds neochebulagic acid (1), ellagic acid (2) and urolithin M5 (3) were isolated from seed extract of Terminalia citrina by activity-guided isolation method. Based on the fact that urolithins are the main and stable intestinal microbiota metabolites of hydrolysable tannins, we found that the metabolite urolithin B repressed translation and secretion of SipC through the Hha-H-NS-HilD-HilC-RtsA-HilA regulatory pathway. The results provide evidence for Terminalia seeds and ellagitannin-rich berries and nuts in regulating intestinal homeostasis and treating bacterial infection.

Pembrolizumab Plus Docetaxel and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Long-term Results from the Phase 1b/2 KEYNOTE-365 Cohort B Study.

BACKGROUND: Patients with metastatic castration-resistant prostate cancer (mCRPC) frequently receive docetaxel after they develop resistance to abiraterone or enzalutamide and need more efficacious treatments. OBJECTIVE: To evaluate the efficacy and safety of pembrolizumab plus docetaxel and prednisone in patients with mCRPC. DESIGN, SETTING, AND PARTICIPANTS: The trial included patients with mCRPC in the phase 1b/2 KEYNOTE-365 cohort B study who were chemotherapy naïve and who experienced failure of or were intolerant to ≥4 wk of abiraterone or enzalutamide for mCRPC with progressive disease within 6 mo of screening. INTERVENTION: Pembrolizumab 200 mg intravenously (IV) every 3 wk (Q3W), docetaxel 75 mg/m2 IV Q3W, and prednisone 5 mg orally twice daily. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoints were safety, the prostate-specific antigen (PSA) response rate, and the objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included time to PSA progression; the disease control rate (DCR) and duration of response (DOR) according to RECIST v1.1 by BICR; ORR, DCR, DOR, and radiographic progression-free survival (rPFS) according to Prostate Cancer Working Group 3-modified RECIST v1.1 by BICR; and overall survival (OS). RESULTS AND LIMITATIONS: Among 104 treated patients, 52 had measurable disease. The median time from allocation to data cutoff (July 9, 2020) was 32.4 mo, during which 101 patients discontinued treatment, 81 (78%) for disease progression. The confirmed PSA response rate was 34% and the confirmed ORR (RECIST v1.1) was 23%. Median rPFS and OS were 8.5 mo and 20.2 mo, respectively. Treatment-related adverse events (TRAEs) occurred in 100 patients (96%). Grade 3-5 TRAEs occurred in 46 patients (44%). Seven AE-related deaths (6.7%) occurred (2 due to treatment-related pneumonitis). Limitations of the study include the single-arm design and small sample size. CONCLUSIONS: Pembrolizumab plus docetaxel and prednisone demonstrated antitumor activity in chemotherapy-naïve patients with mCRPC treated with abiraterone or enzalutamide for mCRPC. Safety was consistent with profiles for the individual agents. Further investigation is warranted. PATIENT SUMMARY: We evaluated the efficacy and safety of the anti-PD-1 antibody pembrolizumab combined with the chemotherapy drug docetaxel and the steroid prednisone for patients with metastatic prostate cancer resistant to androgen deprivation therapy , and who never received chemotherapy. The combination showed antitumor activity and manageable safety in this patient population. This trial is registered on ClinicalTrials.gov as NCT02861573.

Toxoplasma gondii infection in pet cats and their owners in northeastern China:an important public health concern.

BACKGROUND: Limited information about Toxoplasma gondii infection in pet cats and their owners is available in China. METHODS: In this study, blood samples were randomly collected from 306 pet cats and 397 corresponding pet owners in Jilin province, northeastern China. Sera from the pet cats and the pet owners were tested for anti-T. gondii antibodies using an modified agglutination test (MAT) and an enzyme-linked immunosorbent assay (ELISA), respectively. Moreover, the risk factors for T. gondii infection in pet cats and corresponding pet owners were explored. RESULT: In total, 62 sera out of 306 examined pet cats (20.3%) and 18.1% (72/397) pet cat owners were seropositive for T. gondii, respectively. The results of statistical analysis showed that both pet cats and their owners from rural area had significantly higher T. gondii seroprevalence than those from urban area (p < 0.001). Moreover, owners of pet cas who have the knowledge of zoonotic protozoan diseases had a significantly lower T. gondii seroprevalence than those without the knowledge of zoonotic protozoan diseases (p < 0.001). CONCLUSIONS: The present results revealed that the seroprevalence of T. gondii infection are widespread in pet cats and their owners in Jilin province, northeastern China. Residence area and understanding knowledge of zoonotic protozoan diseases are considered to be raleted to the T. gondii infection. Hence, it is necessary to highlight the dangers and protection methods of zoonotic protozoan diseases caused by pet cats, especially in rural area.

Description of a remarkable new species of Isoperla (Plecoptera: Perlodidae), with supplements for Isoperla kozlovi Zhiltzova, 1972 from China.

A remarkable new species of Isoperla Banks, 1906, Isoperla chongxui sp. nov. from Henan Province of China is described and illustrated. The new species is characterized by the conspicuous abdominal tergal processes in males. Comparisons are made between the new species and its congeners. New descriptions and illustrations are provided for Isoperla kozlovi Zhiltzova, 1972 from northeastern China. Isoperla fengi Wu Claassen, 1934 and Isoperla curvispina (Wu, 1938) are considered nomen dubia due to lost types and poor original descriptions.

Complete mitochondrial genome and phylogenetic position of Filchneria songi in Perlodidae (Insecta: Plecoptera).

The complete mitochondrial genome of the perlodid stonefly, Filchneria songi Chen, 2019 was sequenced and analyzed. This double strand, circular molecule is 16,028 bp in length with an A + T content of 70.1%, and contains 13 PCGs, 22 tRNA genes, and two rRNA genes. A 1099-bp long control region was detected, with a high A + T content of 81.9%. Gene arrangement was conserved in the mitogenome of F. songi. Most PCGs use standard start codons and ended with complete stop codons. The phylogenetic analysis supported that F. songi was closely related with species of Perlodes Banks, 1903.

[Dragon-tiger fighting needling therapy in treatment of painful diabetic peripheral neuropathy: a randomized controlled trial].

OBJECTIVE: To compare the clinical therapeutic effect on painful diabetic peripheral neuropathy (PDPN) between dragon-tiger fighting needling and pregabalin capsules. METHODS: A total of 60 patients with PDPN were randomized into an observation group and a control group, 30 cases in each one. On the base of treatment with routine anti-hyperglycaemic measures and nutritional neurotherapy, the dragon-tiger fighting needling was exerted at Sanyinjiao (SP 6), Zusanli (ST 36), Yinlingquan (SP 9) and Xuehai (SP 10) in the observation group, once daily. Pregabalin capsules were prescribed for oral administration in the control group, 75 mg, twice a day. The treatment for 2 weeks was as one course and 2 courses of treatment were required in total. The score of visual analogue scale (VAS), the score of MOS item short form health survey (SF-36) and nerve conduction velocity before and after treatment were compared between the two groups. The clinical therapeutic effect was evaluated in the two groups. RESULTS: After treatment, VAS score was reduced as compared with before treatment in the two groups (P<0.05). The reducing range of VAS score in the observation group was larger than the control group (P<0.05). After treatment, the sensory nerve conduction velocity (SNCV) and motor nerve conduction velocity (MNCV) of median nerve and posterior tibial nerve were all improved as compared with before treatment in the two groups (P<0.05). SNCV and MNCV in the observation group were higher than the control group (P<0.05). After treatment, the score of each item in SF-36 was increased as compared with before treatment in the two groups (P<0.05) and the score of each item in SF-36 in the observation group was higher than the control group (P<0.05). The total effective rate was 86.7% (26/30) in the observation group, better than 60.0% (18/30) in the control group (P<0.05). CONCLUSION: The dragon-tiger fighting needling therapy relieves painful symptoms, improves the quality of life and increases nerve conduction velocity in the patients with diabetic peripheral neuropathy, and the therapeutic effect is better than oral administration of pregabalin capsules.

7,8-Dihydroxyflavone Alleviates Anxiety-Like Behavior Induced by Chronic Alcohol Exposure in Mice Involving Tropomyosin-Related Kinase B in the Amygdala.

Alcohol use-associated disorders are highly comorbid with anxiety disorders; however, their mechanism remains unknown. The amygdala plays a central role in anxiety. We recently found that 7,8-dihydroxyflavone (7,8-DHF) significantly reduces withdrawal symptoms in a rat model of chronic intermittent alcohol (ethanol) exposure. This study aimed to determine the role of 7,8-DHF in regulating anxiety induced by chronic alcohol exposure and its associated underlying mechanism. Male C57BL/6J mice were exposed to chronic intermittent alcohol for 3 weeks followed by alcohol withdrawal for 12 h with or without 7,8-DHF administered intraperitoneally. All mice were tested using an open field test and elevated plus maze to assess anxiety-like behaviors. Synaptic activity and intrinsic excitability in basal and lateral amygdala (BLA) neurons were assessed using electrophysiological recordings. 7,8-DHF alleviated alcohol-induced anxiety-like behavior and attenuated alcohol-induced enhancement of activities in BLA pyramidal neurons. Furthermore, 7,8-DHF prevented alcohol withdrawal-evoked augmentation of glutamatergic transmission in the amygdala and had no effect on GABAergic transmission in the amygdala, as demonstrated by unaltered frequency and amplitude of spontaneous inhibitory postsynaptic currents. Microinjection of K252a, a tropomyosin-related kinase B (TrkB) antagonist, into the BLA blocked the effects of 7,8-DHF on anxiety-like behavior and neuronal activity in the BLA. Our findings suggest that 7,8-DHF alleviates alcohol-induced anxiety-like behavior induced by chronic alcohol exposure through regulation of glutamate transmission involving TrKB in the BLA.

The interaction effects between TLR4 and MMP9 gene polymorphisms contribute to aortic aneurysm risk in a Chinese Han population.

BACKGROUND: A cross-talk between Toll-like receptor 4 (TLR4) and matrix metalloproteinase 9 (MMP9) plays a vital role in aortic pathophysiology. The objective of this study was to evaluate the interactions between TLR4 and MMP9 polymorphisms in the risk of aortic aneurysm (AA) and its subtypes. METHODS: KASP method was used to detect polymorphisms of TLR4 (rs11536889 and rs1927914) and MMP9 (rs17576) in 472 AA patients and 498 controls. According to location and size, AA patients were further classified into abdominal AA (AAA), thoracic AA (TAA), and large AA (>5.0 cm), small AA(≤5.0 cm), respectively. RESULTS: The significant interaction effect of TLR4rs1927914 with MMP9rs17576 polymorphisms was observed for the risk of TAA (Pinteraction = 0.038, OR = 6.186) and large AA (Pinteraction = 0.044, OR = 5.892). There were epistatic effects between TLR4rs1927914 and MMP9rs17576 polymorphisms on the risk of overall AA, AAA, TAA and large AA when they were present together. Moreover, the cumulative effects of the pairwise interaction TLR4rs1927914-MMP9rs17576 were associated with an increased risk of overall AA (Ptrend = 0.032) and AAA (Ptrend = 0.031). CONCLUSIONS: The novel interaction between TLR4rs1927914 and MMP9rs17576 polymorphisms could increase the risk of AA disease or its subtypes by exerting epistatic and cumulative effects.

Rhynchophylline Attenuates Senescence of Endothelial Progenitor Cells by Enhancing Autophagy.

The increase of blood pressure accelerates endothelial progenitor cells (EPCs) senescence, hence a significant reduction in the number of EPCs is common in patients with hypertension. Autophagy is a defense and stress regulation mechanism to assist cell homeostasis and organelle renewal. A growing number of studies have found that autophagy has a positive role in repairing vascular injury, but the potential mechanism between autophagy and senescence of EPCs induced by hypertension has rarely been studied. Therefore, in this study, we aim to explore the relationship between senescence and autophagy, and investigate the protective effect of rhynchophylline (Rhy) on EPCs. In angiotensin II (Ang II)-treated EPCs, enhancing autophagy through rapamycin mitigated Ang II-induced cell senescence, on the contrary, 3-methyladenine aggravated the senescence by weakening autophagy. Similarly, Rhy attenuated senescence and improved cellular function by rescuing the impaired autophagy in Ang II-treated EPCs. Furthermore, we found that Rhy promoted autophagy by activating AMP-activated protein kinase (AMPK) signaling pathway. Our results show that enhanced autophagy attenuates EPCs senescence and Rhy rescues autophagy impairment to protect EPCs against Ang II injury.

Serum matrix metalloproteinase-9 is a valuable biomarker for identification of abdominal and thoracic aortic aneurysm: a case-control study.

BACKGROUND: Matrix metalloproteinase-9 (MMP9) has been reported to play a key role in the pathogenesis of aortic aneurysm. However, few studies have assessed serum MMP9 levels in both abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA). In this study, we investigated the serum levels of MMP9 in aortic aneurysm to evaluate its predictive and diagnostic efficacy for AAA and TAA, and explored the association of MMP9 with circulating laboratory markers. METHODS: A total of 296 subjects were enrolled, including 105 AAA patients, 79 TAA patients and 112 healthy controls. The levels of serum MMP9 were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to control group, both AAA and TAA patients had higher serum MMP9 levels in the overall comparison and subgroup analysis based on subjects aged<65 years, either male or female, hypertension, non-diabetes and non-hyperlipidemia (all P<0.05). Moreover, MMP9 levels were significantly higher in TAA group than those in AAA group in the total comparison, and this discrepancy was also found in the non-diabetes, non-hyperlipidemia and aortic diameter ≥ 5.5 cm subgroup analysis. Serum MMP9 levels were influenced by age and hypertension. There was a positive association of serum MMP9 with CRP (r = 0.33, P < 0.001) and Hcy (r = 0.199, P = 0.033). Multiple logistic analyses showed that serum MMP9 was an independent risk factor for AAA and TAA. Based on receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of MMP9 for predicting TAA was 0.83 with 70% sensitivity and 91% specificity, while the AUC of MMP9 to detect AAA was 0.69 and the sensitivity and specificity were 50% and 88%. CONCLUSIONS: Serum MMP9 was closely related to the existence of aortic aneurysms and could be a valuable marker for the discrimination of aortic aneurysm, especially for TAA.

Development of a TaqMan probe-based quantitative reverse transcription PCR assay for detection of Getah virus RNA.

Getah virus (GETV), a mosquito-borne virus that mainly infects horses and pigs, has emerged and spread in China. We developed a highly specific and reproducible TaqMan probe-based quantitative reverse transcription PCR (RT-qPCR) assay targeting the non-structural protein 1 of GETV, whose detection limit is 25.5 copies/µL, which is 100-fold higher than that of conventional RT-PCR. RT-qPCR was used to detect GETV RNA in mosquito and animal clinical samples, showing that the accuracy of RT-qPCR was higher than that of conventional RT-PCR. The newly developed RT-qPCR assay may be a useful alternative tool for rapid, simple and specific diagnosis of GETV infection.

Combined effects of fruit and vegetables intake and physical activity on the risk of metabolic syndrome among Chinese adults.

BACKGROUND: Unbalanced dietary intake and insufficient physical activity (PA) have been recognized as risk factors for metabolic syndrome (MetS). We aimed to examine the independent and combined effects of fruit and vegetables (FV) intake and PA on MetS. METHODS AND FINDINGS: A cross-sectional survey was conducted among residents of China in 2009, with fasting blood samples collected. Participants were divided into sufficient/insufficient FV intake and adequate/ inadequate PA groups according to self-reported questionnaires. MetS was defined using the NCEP-ATPIII criteria. The difference of individual MetS components was compared across different PA or FV groups. Multivariable logistic regression was used to assess association between FV/PA and the risk of MetS. A total of 7424 adults were included in the current study. MetS was prevalent in 28.7% of participants, with 24.7% and 32.9% in male and female, respectively. Compared with those with inadequate PA and insufficient FV intake, participants with the combination of adequate PA and sufficient FV intake had the lowest risk of MetS (OR = 0.69,95%CI: 0.59-0.82), following by the group with adequate PA time but insufficient FV intake (OR = 0.74, 95%CI:0.65-0.83). CONCLUSION: Findings of the current study show that the combination of sufficient FV intake and adequate PA was significantly associated with reduced MetS risk among adult residents of China.