B-Type Fumonisins in Post-Fermented Tea: Occurrence and Consumer Dietary Exposure in Guangxi, China.

Post-fermented tea (PFT), a commonly consumed beverage worldwide, is characterized by the rapid growth of its microbial groups and the substantial changes they undergo. Consequently, PFT may contain mycotoxins such as B-type fumonisins (FBs). This study aimed to assess the intake of FBs through the consumption of PFT among consumers in Guangxi, China. A novel quantitative method using high-performance liquid chromatography-mass spectrometry was used to determine the FB concentration in PFT products. Additionally, a PFT consumption survey was conducted using a face-to-face questionnaire, recording their body weight and PFT consumption patterns based on a three-day dietary recall method. Finally, hazard index was calculated to estimate the health risk of FBs from the consumption of PFT products in Guangxi. The results revealed that the occurrence of FBs in PFT was 20% (24/120), with a concentration ranging from 2.14 to 18.28 µg/kg. The results of the survey showed that the average daily consumption of PFT by consumers was 9.19 ± 11.14 g. The deterministic risk assessment revealed that only 0.026% of the provisional maximum tolerable daily intake of FBs was consumed through PFT, indicating that FB contamination in PFT is not a public health risk.

[The role and molecular mechanism of miR-494 in disease development and progression].

MicroRNA-494 (miR-494) is a small non-coding RNA located in chromosome 14q32.31 and regulates post-transcriptional gene expression by promoting the degradation of its target mRNAs via binding to the 3' untranslated regions (3'UTR). It has been reported that miR-494 plays an important role in the occurrence, development and prognosis of various diseases. Several signaling pathways modulated by miR-494 including the PTEN/PI3K/AKT, nuclear factor κ-B (NF-κB), mitogen-activated protein kinase (MAPK), transforming growth factor-ß (TGF-ß)/SMAD, and Wnt/ß-catenin are associated with physiological regulation and pathological process in many diseases. The stably expression of miR-494 in the blood stream suggests its potential as a biological marker for disease diagnosis, treatment, and prognosis. Based on recent research, we summarize the role and molecular mechanism of miR-494 in disease development and progression. We also discuss its potential as a marker for clinical diagnosis and prognosis of various diseases.

[Target gene panel method versus whole-exome sequencing in detection of idiopathic hypogonadotropic hypogonadism in males].

Objective: To compare the efficiency of the target gene panel method and whole-exome sequencing (WES) in detecting idiopathic hypogonadotropic hypogonadism (IHH), and select a more suitable gene detection method. METHODS: We selected 24 genes closely related to the molecular pathogenesis of IHH to make up the gene panel, detected the mutation sites in 73 patients with IHH using the panel method, and verified the results of sequencing with the Sanger method. Using the key words "idiopathic hypogonadotropic hypogonadism", we searched databases for relevant literature, calculated the positive rate of IHH detected by WES and compared it with that detected with the panel method. RESULTS: Of the 73 cases of IHH detected with the panel method, 7 were found with pathogenic mutations, including 2 cases of FGFR1, 2 cases of CHD7, 2 cases of KISS1R, and 1 case of NR5A1 mutation. Sanger sequencing showed that the positive rate of the panel method was 9.7%. Of the 1 336 articles retrieved, 5 met the inclusion criteria and were included, in which WES revealed a positive rate of about 30%. CONCLUSIONS: For detection of the diseases with clear mutated genes, the panel method is relatively inexpensive and has a high sequencing depth, while for detection of the diseases with complicated genetic patterns and unclear mutated genes, WES is more efficient. Further studies are needed for choice of the two methods for different purpose of detection./.

Efficacy and Safety of Tocilizumab Treatment COVID-19 Patients: A Case-Control Study and Meta-Analysis.

INTRODUCTION: As the pandemic progresses, the pathophysiology of COVID-19 is becoming more apparent, and the potential for tocilizumab is increasing. However, the clinical efficacy and safety of tocilizumab in the treatment of COVID-19 patients remain unclear. METHODS: To assess the efficacy and safety of tocilizumab treatment in COVID-19 patients, we performed a retrospective case-control study. The study was conducted, including 95 patients treated with tocilizumab plus standard treatment and matched controls with 95 patients treated with standard treatment therapy by propensity score from February to April 2020. We searched some databases using the search terms for studies published from January 1, 2020, to June 1, 2021. RESULTS: Our case-control study found a lower mortality rate in the tocilizumab treatment group than in the standard treatment group (9.47% versus 16.84%, P = 0.134), but the results were not statistically significant. We also found that the mortality rate in tocilizumab treatment groups was significantly lower than in the standard treatment group in the stratified ICU analysis (OR 0.52, 95% CI 0.44-0.61, P = 0.048 and OR 0.31, 95% CI 0.10-0.99, P = 0.044). We selected 49 studies (including 6568 cases and 11,660 controls) that met the inclusion criteria in the meta-analysis. In the overall analysis, we performed a meta-analysis that showed significantly decreased mortality after patients received tocilizumab (OR 0.81, 95% CI 0.69-0.95, P = 0.008). We also revealed significant associations within some subgroups. The sequential trial analysis showed a true-positive result. No significant associations were observed between tocilizumab and elevated secondary infection risk, discharge, adverse events, and mechanical ventilation in the overall analysis. CONCLUSION: Tocilizumab significantly decreased mortality in COVID-19 patients with no increased discharge, secondary infection risk, adverse events, and mechanical ventilation in a meta-analysis. Our data suggest that clinicians should pay attention to tocilizumab therapy as an effective and safe treatment for COVID-19 patients.

Lifelong Aerobic Exercise Alleviates Sarcopenia by Activating Autophagy and Inhibiting Protein Degradation via the AMPK/PGC-1α Signaling Pathway.

Sarcopenia is an aging-induced syndrome characterized by a progressive reduction of skeletal muscle mass and strength. Increasing evidence has attested that appropriate and scientific exercise could induce autophagy or optimize the functional status of autophagy, which plays a critical role in senescent muscular dystrophy. As a publicly recognized strategy for extending lifespan and improving the health of the elderly, the underlying mechanisms of lifelong regular aerobic exercise for the prevention of sarcopenia have not been fully elucidated. To explore the role of lifelong aerobic exercise in the beneficial regulation of autophagic signaling pathways in senescent skeletal muscle, the natural aging mice were used as the sarcopenia model and subjected to lifelong treadmill running to evaluate corresponding parameters related to skeletal muscle atrophy and autophagic signaling pathways. Compared with the young control mice, the aged mice showed a significant reduction in skeletal muscle mass, gastrocnemius muscle weight/body weight (GMW/BW) ratio, and cross-sectional areas (CSA) of skeletal muscle fibers (p < 0.01). In contrast, lifelong aerobic exercise effectively rescued these reduced biomarkers associated with muscle atrophy. Moreover, as shown in the activated AMPK/PGC-1α signaling pathway, lifelong aerobic exercise successfully prevented the aging-induced impairment of the ubiquitin-proteasome system (UPS), excessive apoptosis, defective autophagy, and mitochondrial dysfunction. The exercise-induced autophagy suppressed the key regulatory components of the UPS, inhibited excessive apoptosis, and optimized mitochondrial quality control, thereby preventing and delaying aging-induced skeletal muscle atrophy.

Upregulated IL-6 Indicates a Poor COVID-19 Prognosis: A Call for Tocilizumab and Convalescent Plasma Treatment.

A comprehensive understanding of the dynamic changes in interleukin-6 (IL-6) levels is essential for monitoring and treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). By analyzing the correlations between IL-6 levels and health conditions, underlying diseases, several key laboratory detection indices, and the prognosis of 1,473 patients with the coronavirus disease 2019 (COVID-19), the role of IL-6 during SARS-CoV-2 infection was demonstrated. Our results indicated that IL-6 levels were closely related to age, sex, body temperature, oxygen saturation (SpO2) of blood, and underlying diseases. As a stable indicator, the changes in IL-6 levels could indicate the inflammatory conditions during a viral infection. Two specific treatments, namely, tocilizumab and convalescent plasma therapy (CPT), decreased the level of IL-6 and relieved inflammation. CPT has an important role in the therapy for patients with critical COVID-19. We also found that patients with IL-6 levels, which were 30-fold higher than the normal level, had a poor prognosis compared to patients with lower levels of IL-6.

3044 Cases reveal important prognosis signatures of COVID-19 patients.

Critical patients and intensive care unit (ICU) patients are the main population of COVID-19 deaths. Therefore, establishing a reliable method is necessary for COVID-19 patients to distinguish patients who may have critical symptoms from other patients. In this retrospective study, we firstly evaluated the effects of 54 laboratory indicators on critical illness and death in 3044 COVID-19 patients from the Huoshenshan hospital in Wuhan, China. Secondly, we identify the eight most important prognostic indicators (neutrophil percentage, procalcitonin, neutrophil absolute value, C-reactive protein, albumin, interleukin-6, lymphocyte absolute value and myoglobin) by using the random forest algorithm, and find that dynamic changes of the eight prognostic indicators present significantly distinct within differently clinical severities. Thirdly, our study reveals that a model containing age and these eight prognostic indicators can accurately predict which patients may develop serious illness or death. Fourthly, our results demonstrate that different genders have different critical illness rates compared with different ages, in particular the mortality is more likely to be attributed to some key genes (e.g. ACE2, TMPRSS2 and FURIN) by combining the analysis of public lung single cells and bulk transcriptome data. Taken together, we urge that the prognostic model and first-hand clinical trial data generated in this study have important clinical practical significance for predicting and exploring the disease progression of COVID-19 patients.

The paradoxical problem with COVID-19 ocular infection: Moderate clinical manifestation and potential infection risk.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which induced mainly the respiratory damage also caused ocular surface symptoms. However, the detailed description of ocular manifestations, severity fluctuations in confirmed COVID-19 adult patients still lacked. We analyzed onset clinical symptoms and duration, ocular symptoms, needs for medication, outcomes in 28 conjunctivitis patients who were extracted from 3198 COVID-19 patients hospitalized in Huoshenshan Hospital and Taikangtongji Hospital, Wuhan, China. The expression levels of ACE2, TMPRSS2, ANPEP, DPP4, NRP1 on fetal and adult ocular surface and mouse lacrimal glands were assessed by single cell seq analysis. Our results indicated that conjunctivitis was a rare and self-limited complication in adults with COVID-19 while the existence of coronavirus receptors on human ocular surface and mouse lacrimal glands indicated the risk of SARS-CoV-2 infection. Our research firstly examined SARS-CoV-2 receptors, including the new discovered one, NRP1, on the fetal ocular surface and in the mouse lacrimal glands.

Clinical outcomes for COVID-19 patients with diabetes mellitus treated with convalescent plasma transfusion in Wuhan, China.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is wreaking havoc on public health systems worldwide. The diagnosis of COVID-19 is well defined, but efficacious treatment is lacking. There is a big gap in knowledge regarding COVID-19 patients receiving convalescent plasma transfusion (CPT), especially those also suffering from diabetes mellitus (DM). In this study, among 3059 COVID-19 patients admitted to Wuhan Huoshenshan Hospital of China, we documented the characteristics of 39 COVID-19 patients with DM receiving CPT and compared their baseline information and clinical outcomes to COVID-19 patients with DM receiving conventional treatment. We also performed the propensity-matched comparison of COVID-19 patients with DM between conventional treatment and CPT. The CPT was efficacious and beneficial for COVID-19 patients with DM, including severe or critically ill patients, without obvious adverse effects. Our data demonstrated that CPT significantly improved the clinical outcomes of COVID-19 patients with DM, especially the cure rate and duration of hospitalization compared with that in COVID-19 patients with DM receiving conventional treatment. This study not only provided a deeper understanding of characteristics in COVID-19 patients with DM receiving CPT but also highlighted the efficaciousness of CPT for COVID-19 patients with DM.

Potential False-Positive and False-Negative Results for COVID-19 IgG/IgM Antibody Testing After Heat-Inactivation.

Objectives: With the worldwide spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), various antibody detection kits have been developed to test for SARS-CoV-2- specific IgG, IgM, and total antibody. However, the use of different testing methods under various heat-inactivation conditions might affect the COVID-19 detection results. Methods: Seven different antibody detection kits produced by four manufacturers for detection of SARS-CoV-2 IgG, IgM, and total antibody were tested at Wuhan Huoshenshan Hospital, China. Most of the kits used the indirect immunity, capture, and double-antigen sandwich methods. The effects of various heat-inactivation conditions on SARS-CoV-2-specific IgG, IgM, and total antibody detection were analyzed for the different test methods. Results: Using the indirect immunity method, values for SARS-CoV-2 IgG antibody significantly increased and those for IgM antibody decreased with increasing temperature of heat-inactivation using indirect immunity method. However, values for SARS-CoV-2 IgM and total antibody showed no change when the capture and double-antigen sandwich methods were used. The changes in IgG and IgM antibody values with the indirect immunity method indicated that heat-inactivation could affect COVID-19 detection results obtained using this method. In particular, 18 (22.2%) SARS-CoV-2 IgM positive samples were detected as negative with heat-inactivation at 65°C for 30 min, and one (25%) IgG negative sample was detected as positive after heat-inactivation at 56°C for 60 min and 60°C for 30 min. Conclusions: Heat-inactivation could increase SARS-CoV-2 IgG antibody values, and decrease IgM antibody values, causing potential false-positive or false-negative results for COVID-19 antibody detection using the indirect immunity method. Thus, before conducting antibody testing, the testing platforms should be evaluated in accordance with the relevant requirements to ensure accurate COVID-19 detection results.

A fully substituted 3-silolene functions as promising building block for hyperbranched poly(silylenevinylene).

A 3-silolene derivative, 2,2,5,5-tetrakis(dimethylsilyl)-1,1-dimethyl-3,4-diphenyl-3-silolene (TDMSHS), is first synthesized and characterized by X-ray diffraction crystallography and spectroscopic methods. Hydrosilylation polymerization of TDMSHS with 1,1-dimethyl-2,5-bis(4-ethynylphenyl)-3,4-diphenylsilole in the presence of Karstedt's catalyst generates a stereoregular silole-containing hyperbranched poly(silylenevinylene) (hb-SPSV) with a high molecular weight (M(w) = 146,000, M(w)/M(n) = 1.5) in high yield (≈95%). hb-SPSV exhibits excellent thermal stability and strong fluorescence, and the emission of its aggregates in aqueous mixture can be quenched efficiently by picric acid with large quenching constants K(SV) up to 414400 M(-1).

[Study on phenotypic and genotypic characterization of clinical multidrug-resistant Escherichia coli isolates].

OBJECTIVE: To study the mechanisms on drug susceptibility and resistance of clinically multidrug-resistant Escherichia coli isolates, to provide information on related treatment. METHODS: The susceptibility of E. coli strains that isolated from different kinds of samples in the last 3 years on drugs was analyzed by agar dilution test, with strains that exhibiting resistances to cefotaxime, ciprofloxacin and amikacin simultaneously collected for further analysis. Resistant genes which mediate resistance to ß-lactamases, fluoroquinolone and aminoglycoside as well as phylogenic type were detected by PCR amplification while genetic relation was analyzed by PFGE. Transferability of resistant plasmids was identified by conjugation test. RESULTS: In total, 137 multidrug-resistant E. coli isolates were collected. Only 1% of the isolates exhibited resistance to both imipenem and meropenem while 4% of the strains were resistant to piperacillin/tazobactam. Most (85%) of the isolates were positive to ESBL and majority of them produced CTX-M. Target substitution and production of methylases were the main mechanisms causing resistance to fluoroquinolones and aminoglycosides respectively. CONCLUSION: The main source of clinical multidrug-resistance was collected from urine samples. Carbapenem and enzyme inhibitor-containing antibiotics seemed to be the available antibiotics that were sensitivity to the clinically multidrug-resistant E. coli isolates.

[Immunosuppressant dexamethasone can significantly extend the expression of hepatitis B virus antigens in the HBV mouse model by hydrodynamic transfection method].

To develop a HBV infection mouse model by hydrodynamic-based transfection and further to optimize the method of development of HBV infection mouse model. We first developed a construct which contained inverted terminal repeat elements (ITR) of adeno-associated virus (AAV) and 1. 3 copies of HBV genome (ayw subtype). The pAAV-HBV1. 3 DNA was then injected hydrodynamically into the tail veins of C57BL/6 mice in 5 seconds. The virus load in serum and liver was assayed by ELISA and Real-time PCR. The expression of virus antigen and the pathologic changes of liver were analyzed by HE and immunohistochemical staining. Meanwhile, to develop HBV transfected immunosuppressied mouse, mice were injected intraperitoneally triple with 0.2 ml dexamethason (50 mg/kg) every two days before HBV transfection. The levels of HBsAg and HBeAg were assayed by ELISA. Our data showed: (1) HBsAg and HBeAg were positive (100%) in serum and liver of experimental normal mouse at day 10 after HBV transfection, and became negative at day 30 and day 60. Meanwhile the viral load in serum and liver in experimental group was significantly higher than that in control group at day 10, 30 and 60 after HBV transfection (P < 0.01, P < 0.05, respectively). (2) HBsAg and HBeAg in serum in immunosuppressed mouse model were positive until 60 days. In conclusion, a HBV infection mouse model was developed successfully by hydrodynamic-based transfection. By suppressing the immune status of mice injected with dexamethasone, the expression of HBV antigens was extended longer than that in normal adult mice. These models pave a way for HBV research and evaluation of HBV vaccine and drug development.