Rationale and Design of the ADIDAS Study: Association Between Dapagliflozin-Induced Improvement and Anemia in Heart Failure Patients.

BACKGROUND: Heart failure (HF) is one of the most serious health concerns worldwide. Anemia is a highly prevalent comorbidity and outcome predictor in HF patients. Sodium glucose co-transport 2 (SGLT2) inhibitors have been demonstrated to reduce the risk of cardiovascular death and HF hospitalization in HF patients. PURPOSE: This investigator-initiated, interventional, prospective, double-blind, multicenter study is designed to investigate whether anemia correction is one of the prerequisites and determinants related to the beneficial effects of dapagliflozin in HF patients. METHODS AND RESULTS: Up to 2030 HF participants receiving standard care will be randomly assigned to either oral dapagliflozin 10 mg once daily or placebo 10 mg once daily for 12 months. The primary outcome is the composite incidence of hospital admission for HF and all-cause death. Secondary outcomes include change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) score and change in 6-min walk distance and hemoglobin level. Patients will be followed for 12 months after randomization. CONCLUSIONS: The ADIDAS trial offers an opportunity to assess the hemoglobin change and association between hemoglobin change and readmissions due to heart failure and all-cause death in patients with heart failure treated with dapagliflozin or placebo. This study could highlight if dynamic hemoglobin change is related to the outcome for HF patients. TRIAL REGISTRATION: ClinicalTrials.gov ; NCT04707261. Registration date, 2020/12/01, "retrospectively registered".

A First Expression, Purification and Characterization of Endo-ß-1,3-Glucanase from Penicillium expansum.

ß-1,3-glucanase plays an important role in the biodegradation, reconstruction, and development of ß-1,3-glucan. An endo-ß-1,3-glucanase which was encoded by PeBgl1 was expressed, purified and characterized from Penicillium expansum for the first time. The PeBgl1 gene was amplified and transformed into the competent cells of E. coli Rosetta strain with the help of the pET-30a cloning vector. The recombinant protein PeBgl1 was expressed successfully at the induction conditions of 0.8 mmol/L IPTG at 16 °C for 16 h and then was purified by nickel ion affinity chromatography. The optimum reaction temperature of PeBgl1 was 55 °C and it had maximal activity at pH 6.0 according to the enzymatic analysis. Na2HPO4-NaH2PO4 buffer (pH 6.0) and NaCl have inhibitory and enhancing effects on the enzyme activities, respectively. SDS, TritonX-100 and some metal ions (Mg2+, Ca2+, Ba2+, Cu2+, and Zn2+) have an inhibitory effect on the enzyme activity. The results showed that PeBgl1 protein has good enzyme activity at 50-60 °C and at pH 5.0-9.0, and it is not a metal dependent enzyme, which makes it robust for storage and transportation, ultimately holding great promise in green biotechnology and biorefining.

Proteomic Analysis of Apple Response to Penicillium expansum Infection Based on Label-Free and Parallel Reaction Monitoring Techniques.

Blue mold, caused by Penicillium expansum, is the most destructive fungal disease of apples and causes great losses during the post-harvest storage of the fruit. Although some apple cultivars are resistant to P. expansum, there has been little information on the molecular mechanism of resistance. In this study, differential proteomic analysis was performed on apple samples infected and uninfected with P. expansum. Parallel reaction monitoring (PRM) technology was used to target and verify the expression of candidate proteins. The label-free technique identified 343 differentially expressed proteins, which were mainly associated with defense responses, metal ion binding, stress responses, and oxidative phosphorylation. The differential expression of enzymes related to reactive oxygen species (ROS) synthesis and scavenging, the activation of defense-related metabolic pathways, and the further production of pathogenesis-related proteins (PR proteins) during P. expansum infection in apples, and direct resistance to pathogen invasion were determined. This study reveals the mechanisms of apple response at the proteomic level with 9 h of P. expansum infection.

Clinical metagenomic sequencing for diagnosis of pulmonary tuberculosis.

OBJECTIVES: The aim of this study is to investigate the clinical usefulness of metagenomic Next-generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) samples to discriminate pulmonary tuberculosis (PTB) from Non-TB community-acquired pneumonia (CAP) in PTB suspects. METHODS: We investigate the performance of mNGS on BALF samples from 110 PTB suspects, in comparison with conventional microbiological testing (solid media culture, acid-fast bacilli staining (AFS), Xpert) of BALF or sputum samples and final clinical diagnosis. RESULTS: We finally clinically diagnosed 48 cases of pulmonary tuberculosis patients and 62 cases of non-tuberculosis patients. Comparing to the final clinical diagnosis, mNGS produced a sensitivity of 47.92%, which was similar to that of Xpert (45.83%) and culture (46.81%), but much higher than that of AFS (29.17%) for TB diagnosis in BALF samples. Apart from detecting Mycobacterium tuberculosis, mNGS also identified mixed infections in PTB patients, including 3 fungal cases and 1 bacteria case. Meanwhile, mNGS efficiently identified 14 of 22 (63.63%) cases of non-tuberculous mycobacteria (NTM), 7 cases of fungi, 1 case of viral infection, and other common bacterial pathogens in Non-PTB group. Finally, mNGS identified 67.23% infection cases within 3 days, while the conventional methods identified 49.58% infection cases for over 90 days. CONCLUSION: Our data show that mNGS of BALF represents a potentially effective tool for the rapid diagnosis of PTB suspects.

Pooled analysis of prognostic value and clinical significance of Rab1A expression in human solid tumors.

BACKGROUND: This study aims to assess the relationship between Rab1A expression and clinicopathological parameters and prognosis of patients with human solid cancer by summarizing the studies included. METHODS: PubMed, EMBASE, The Cochrane Library, and other sources were searched for relative studies. The risk ratios (RRs) and confidence interval (CI) were used to assess association between Rab1A expression and clinical parameters and prognosis in solid cancer patients. RESULTS: Eight studies were included in the final analysis with 800 patients. The results revealed that expression of Rab1A was significantly related with differentiation (RR = 0.883, 95%CI = 0.782-0.997, P = .044), lymph node metastasis (RR = 0.835, 95%CI = 0.753-0.926, P = .001), tumor-lymph node-metastasis (TNM) stage (RR = 1.190, 95%CI = 1.071-1.322, P < .001) and tumor size (RR = 0.818, 95%CI = 0.730-0.915, P < .001). What is more, no significant difference was seen in 1-year survival between high and low expression of Rab1A in multiple malignancies (RR = 0.855, 95%CI = 0.697-1.050, P = .136). However, increased Rab1A revealed poorer prognosis with 2-year survival (RR = 0.760, 95%CI = 0.701-0.824, P < .001), 3-year survival (RR = 0.669, 95%CI = 0.604-0.742, P < .001), 4-year survival (RR = 0.622, 95%CI = 0.554-0.698, P < .001) and 5-year survival (RR = 0.525, 95%CI = 0.458-0.698, P < .001). Expression of Rab1A was increased obviously in solid cancer tissues compared with the adjacent normal tissue (RR = 4.78, 95%CI 4.05-5.63, P = .015). CONCLUSION: This study revealed Rab1A expression links closely with tumor size, differentiation, lymph node metastasis, TNM stage and poor prognosis of human solid cancer patients. It may act as a biomarker of prognosis and a novel therapeutic target in solid cancer.

Drug resistance mutation profiles of the drug-naïve and first-line regimen-treated HIV-1-infected population of Suzhou, China.

Little is known about the prevalence of drug-resistant mutations in HIV-1-positive individuals in Suzhou, China. To elucidate the transmitted drug resistance (TDR) and acquired drug resistance mutation (ADR) profiles, we collected blood specimens from 127 drug-naïve and 117 first-line drug-treated HIV-1-infected individuals sampled from 2014 to 2016 in Suzhou. We successfully amplified pol fragments from 100 drug-naïve and 20 drug-treated samples. We then determined the drug-resistant mutations to protease (PR) and reverse-transcriptase (RT) inhibitors according to the Stanford drug resistance database. Overall, 11 and 13 individuals had transmitted (drug-naïve group) and acquired (treated group) resistance mutations, respectively. Six transmitted drug-resistant mutations were found, including two mutations (L33F and L76V) in the protease region and four (K70N/E and V179D/E) in the RT region. Only L76V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors. All 13 treated participants who had major drug resistance mutations demonstrated intermediate to high resistance to efavirenz and nevirapine, and six had a treatment duration of less than three months. No major mutations to RT inhibitors were found, implying that the epidemic of transmitted resistance mutations was not significant in this area. Our results suggest that more frequent virus load and drug resistance mutation tests should be conducted for individuals receiving antiretroviral treatment, especially for newly treated patients. Our research provides insights into the occurrence of HIV-1 drug resistance in Suzhou and will help to optimize the treatment strategy for this population.