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Six oxazolomycins (1–6) were isolated from the fermentation broth of a soil-borne bacterial strain, Streptomyces glaucus.

Dihuang Yinzi, as a classical Chinese medicine prescription, plays an important role for the treatment of ischemic stroke. Gut microbiota play a functional role for the expression of proinflammatory cytokines and anti-inflammatory cytokines, which further affect central nervous system and change brain function. Our research confirmed that Dihuang Yinzi can exert brain protection by inhibiting inflammatory reaction. Dihuang Yinzi can significantly decrease the contents of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-17 (IL-17) in brain, serum, and colon tissues and increase the contents of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) in cerebral ischemia-reperfusion model rats. The results of 16s rRNA high-throughput sequencing showed that Dihuang Yinzi had a significant effect on microbiome in rats. The firmicutes, bacteroidetes, and proteobacteria were dominant in Dihuang Yinzi group. The content of firmicutes increased with the increase of dosage of Dihuang Yinzi. Especially, the content of actinomycetes in the high-dose group was higher than other groups. At the genus level, the number of bacteroides in the antibiotic groups was significantly higher than that in the other treatment groups. The results suggest that Dihuang Yinzi may play important roles in treatment of ischemic stroke by regulating the gut microbiota and the inflammatory reaction in the colon tissues, serum, and brain of the model rats, to verify the scientific nature of this prescription in relieving brain inflammatory reaction and brain injury by this way and to reveal the brain-gut related mechanism of Dihuang Yinzi in treating ischemic stroke.

Background Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) RNA was found in the intestines and feces, but its clinical significance is not completely clear. We aim to characterize the longitudinal test results of SARS‐CoV‐2 RNA in anal swabs and to explore the association with disease severity. Methods We included laboratory‐confirmed coronavirus disease 2019 (COVID‐19) patients, who were hospitalized in Guangzhou Eighth People's Hospital and excluded those who had not received anal swabs for SARS‐COV‐2 RNA testing. Epidemiological, clinical, and laboratory data were obtained. Throat swabs and anal swabs were collected periodically for SARS‐COV‐2 RNA detection. Results Two hundred and seventeen eligible patients (median aged 50 years, 50.2% were females) were analyzed. 21.2% (46/217) of the patients were detected with SARS‐CoV‐2 RNA in anal swabs. The duration of viral RNA was longer, but the viral load was lower in anal swabs than throat swabs in the early stage of the disease. During a median follow‐up of 20 days, 30 (13.8%) patients were admitted to the intensive care unit (ICU) for high‐flow nasal cannula or higher‐level oxygen support measures to correct hypoxemia. Detectable viral RNA in anal swabs (adjusted hazard ratio [aHR], 2.50; 95% confidence interval [CI], 1.20‐5.24), increased C‐reactive protein (aHR, 3.14; 95% CI, 1.35‐7.32) and lymphocytopenia (aHR, 3.12; 95% CI, 1.46‐6.67) were independently associated with ICU admission. The cumulative incidence of ICU admission was higher among patients with detectable viral RNA in anal swabs (26.3% vs 10.7%, P = .006). Conclusion Detectable SARS‐CoV‐2 RNA in the digestive tract was a potential warning indicator of severe disease., Highlights We longitudinally detected the SARS‐CoV‐2 RNA in anal swabs and throat swabs, and explored the association with disease severity of COVID‐19.21.2% of COVID‐19 patients were detectable for SARS‐CoV‐2 RNA in annal swabs. The duration of virus was longer, but the viral load was lower in anal swabs than throat swabs.Patients with detectable viral RNA in anal swabs had a 2.5‐fold higher risk of ICU admission (26.3% vs. 10.7%, P = 0.006).Detectable SARS‐CoV‐2 RNA in the digestive tract was a potential warning indicator of severe disease. Screening the virus in digestive tract, close monitoring and early intervention of patients with detectable virus are needed.

Objective The purpose of this study was to investigate the expression of miRNA-223 and NLRP3 in IgA patients and the intervention of traditional Chinese medicine (TCM), so as to realize the basic pathological changes of IgA patients, the expression of miRNA-223 and NLRP3 in IgA patients and the changes of patients' body indexes before and after the treatment of TCM. Methods Firstly, according to the clinical data, patients with IgA nephropathy were divided into different groups according to their pathological changes. After that, the chemical sections and staining steps of the immune kidney were carried out. Immunohistochemical pv-9000 two-step method was used to stain it. By this method, miRNA-223 and NLRP3 genes in kidney were determined. After that, the image analysis method was used for semi quantitative experiment. Finally, the intervention of TCM was used to study the changes of indicators before and after treatment. Results miRNA-223 and NLRP3 genes could be found mainly in the cytoplasm of renal tubular epithelial cells and the interstitium of monocyte in renal tissue, and there were significant differences between miRNA-223 and NLRP3 genes in the expression levels of proteinuria alone, hematuria albuminuria alone and hematuria alone. There was a positive correlation between miRNA-223 and NLRP3 expression and 24-hour urinary protein in IgA nephropathy. In addition, it also had positive correlation with MCP-1 and IL-18. Conclusion This study could provide some direction and guidance for clinical diagnosis and treatment of IgA nephropathy.

Benzophenone glycosides are a major type of polyphenols present in guava. To date, there is still poor understanding of the relationship between benzophenone glycosides and the hepatoprotective effects attributed to this edible fruit. Herein, the protective effects of guavinoside B (GUB), a main benzophenone glycoside present in guava fruit, against acetaminophen (APAP)-induced liver injury were investigated in vitro and in vivo. Fluorescence measurement demonstrated that GUB (at a concentration of 30 μM) significantly reduced the intracellular ROS levels in APAP-treated HepG2 cells. In addition, GUB (100 mg kg-1 d-1) pretreatment markedly alleviated APAP-induced hepatocyte infiltration and necrosis in C57BL/6 mice, and improved serum and hepatic biochemical parameters, such as ALT, AST, SOD, GSH, ROS, MDA, and TNF-α levels. RT-PCR and western blot experiments revealed that GUB up-regulated Nrf2, GCLC and NQO1, while reducing p-JNK gene expression in the liver. The fermentation experiment further revealed that the displayed beneficial effects of GUB in vivo might be related to the gut microbial metabolite gallic acid. These promising data suggested that GUB showed potent hepatoprotective effects through regulating the Nrf2 and JNK signaling pathways. Further investigation of the absorption and metabolism of benzophenones would be warranted to promote the utilization of these phenolics as functional food ingredients against oxidative stress-induced chronic diseases.

The current study was designed to investigate the inhibitory effects of dichloromethane extract of fermentation broth by co-culture of Morchella esculenta and Coprinus comatus (DCMM) on human glioma U251 cells in vitro and its possible underlying mechanisms. The proliferation of U251 cells was inhibited by DCMM with different concentrations by the CCK-8 assay. Besides, flow cytometry assay was used to evaluate the DCMM promoted U251 cell apoptosis rate in a dose-dependent manner. DCMM with different concentrations (10 μg·mL-1, 20 μg·mL-1, and 40 μg·mL-1) significantly enhanced the expression of caspases-3 activity after 24 h. In addition, DCMM with different concentrations significantly increased caspase-3 and Bax, and decreased Bcl-2 expressions at both mRNA and protein levels. DCMM can remarkably inhibit the proliferation and promote cell apoptosis of human glioma U251 cells. The possible underlying mechanisms could be related to induction of apoptosis of human glioma U251 cells by mitochondrial intrinsic pathway.

Background Little is known about the ultrasonographic features of fetal isolated redundant foramen ovale flap (RFOF). Additionally, false positive diagnosis of aortic coarctation (CoA) may be related to the presence of an RFOF. This study aimed to explore the ultrasonographic features of RFOF and its differential diagnosis with CoA. Methods This was a retrospective cohort study that included 54 fetuses: 15 with isolated RFOF, 9 with CoA, and 30 normal fetuses of matched gestational age. The correlations of foramen ovale flap diameter (FOFD)/left atrial diameter (LAD) with right atrial diameter (RAD)/LAD, right ventricular diameter (RVD)/left ventricular diameter (LVD), and pulmonary artery diameter (PAD)/aortic diameter (AoD) were analyzed, and a quadratic regression model was established. Differences in FOFD/LAD, RAD/LAD, RVD/LVD, PAD/AoD, and aortic isthmus diameter were compared among the three groups. Results (1) Noticeable RAD/LAD, RVD/LVD, and PAD/AoD increases, aortic arch dysplasia, and aortic isthmus narrowing were found in the RFOF group (all p r = 0.825, 0.862, 0.846, all p p > 0.05). Conclusions Isolated RFOF has specific ultrasound features, and the degree of disproportion between the left and right heart is consistent with the severity of RFOF. Measurement and calculation of FOFD/LAD may help distinguish between RFOF and CoA.

Between 30% and 50% of survivors of cardiac arrest (CA) suffer from cognitive deficits. However, no effective medical intervention is available to alleviate cognitive deficits. Baclofen is known to protect damaged neurons, but researchers have still not clearly whether baclofen alleviates CA-induced cognitive deficits. The present study aimed to investigate whether baclofen protects against post-CA cognitive deficits and to reveal the protective mechanism of baclofen. Rats underwent 10 min of asphyxia to establish CA models. Intriguingly, our results indicated that baclofen improved spatial memory 72 h after CA. Baclofen increased plasticity-related protein (PSD95, and GAP43) expression in the brain after CA. Baclofen reduced microglial number and the release of inflammatory factors (IL-1β and IL-18). Furthermore, baclofen significantly reduced the expression of pyroptosis-related molecules after CA. Notably, activation of NLRP3 abolished the anti-pyroptosis effect of baclofen and reduced the expression of synaptic plasticity-related proteins after CA. Taken together, this study first shows that baclofen attenuates cognitive deficits induced by brain injury after CA. The mechanism is at least partially attributed to baclofen regulating pyroptosis by inhibition of NLRP3 activation.

Talaromycosis is a life-threatening fungal disease commonly seen in patients with acquired immunodeficiency syndrome (AIDS), which is endemic in Southern China and Southeast countries. The diagnostic methods available for talaromycosis are relatively time-consuming and yield a high mortality. Therefore, early diagnosis of talaromycosis is extremely important. We aimed to determine a potential method for assisting in its early diagnosis. A total of 283 patients with AIDS admitted to our hospital were prospectively included in this cross-sectional study and divided into those with Talaromyces marneffei (TSM group, n=93) and those without Talaromyces marneffei (non-TSM group, n=190). The diagnostic accuracy of the Mp1p enzyme immunoassay (EIA), galactomannan (GM) assay, and blood culture performed within 3 days of hospitalisation were evaluated, using talaromycosis confirmed by culture and/or pathology as the gold standard. The positivity rates in the Mp1p EIA, GM assay, and blood culture were 72%, 64.5%, and 81.7%, respectively, in the TSM group. The sensitivity, specificity, and positive and negative predictive values of the Mp1p EIA were 72.0% (67/93), 96.8% (184/190), 91.8% (67/73), and 87.6% (184/210), respectively. The Mp1p EIA showed a substantial agreement with the gold standard (kappa: 0.729) and superiority to the GM assay (kappa: 0.603); it also showed a superior diagnostic accuracy in the patients with CD4+ counts of

Objectives To comprehensively analyse the prevalence of drug resistance and the transmission characteristics of CRF59_01B strains in infected patients in Guangdong, China. Methods CRF59_01B-infected individuals were recruited, and the HIV-1 pol region was amplified. Drug resistance-associated mutations (DRMs) and antiretroviral susceptibility were examined using the Stanford University HIV Drug Resistance Database to analyse pretreatment drug resistance (PDR) and acquired drug resistance (ADR). Genetic transmission networks were extracted from the maximum likelihood phylogenetic tree with Cluster Picker and visualized with Cytoscape. Results Two hundred and twenty-five CRF59_01B-infected individuals, comprising 35 ART-experienced and 190 ART-naive individuals, were recruited. No patients harboured PI DRMs, 5.33% (12/225) of the patients harboured NRTI DRMs and 11.11% (25/225) of the patients harboured NNRTI DRMs. The overall prevalence of strains with ADR was 51.43% (18/35), while the prevalence of strains with PDR was 2.63% (5/190). A total of 20 transmission networks, involving 25.78% (58/225) database-derived sequences, were identified. The networks ranged in size from 2 to 10 individuals, of which most (55.00%, 11/20) were made up of two individuals. Among the 225 study subjects, 9.78% (22/225) had 1 link and 16.00% (36/225) had ≥2 links. Conclusions The overall prevalence of CRF59_01B strains with ADR among the ART-experienced patients was high. Although the overall prevalence of CRF59_01B strains with PDR among the ART-naive patients was low, it is necessary to remain vigilant regarding some important DRMs.

Our previous studies have found that caprylic acid (C8:0) can improve blood lipids and reduce inflammation levels and may be related to the upregulation of the p-JAK2/p-STAT3 pathway by ABCA1. This study aims to investigate the effects of C8:0 and eicosapentaenoic acid (EPA) on lipids, inflammatory levels, and the JAK2/STAT3 pathway in ABCA1-deficient mice (ABCA1−/−) and ABCA1 knock-down (ABCA1-KD) RAW 264.7 cells. Twenty 6-week ABCA1−/− mice were randomly divided into four groups and fed a high-fat diet, or a diet of 2% C8:0, 2% palmitic acid (C16:0) or 2% EPA for 8 weeks, respectively. The RAW 264.7 cells were divided into the control or control + LPS group, and the ABCA1-KD RAW 264.7 cells were divided into ABCA1-KD with LPS (LPS group), ABCA1-KD with LPS + C8:0 (C8:0 group), and ABCA1-KD with LPS + EPA (EPA group). Serum lipid profiles and inflammatory levels were measured, and ABCA1 and JAK2/STAT3 mRNA and protein expressions were determined by RT-PCR and Western blot analyses, respectively. Our results showed that serum lipid and inflammatory levels increased in ABCA1−/− mice (p < 0.05). After the intervention of different fatty acids in ABCA1−/− mice, TG and TNF-α were significantly lower, while MCP-1 increased significantly in the C8:0 group (p < 0.05); however, LDL-C, TC, TNF-α, IL-6, and MCP-1 levels decreased significantly and IL-10 increased significantly in the EPA group (p < 0.05). In the aorta of ABCA1−/− mice, C8:0 significantly decreased p-STAT3 and p-JAK2 mRNA, while EPA significantly reduced TLR4 and NF-κBp65 mRNA. In the ABCA1-KD RAW 264.7 cells, TNF-α and MCP-1 were increased significantly and IL-10 and IL-1β were significantly decreased in the C8:0 group (p < 0.05). The protein expressions of ABCA1 and p-JAK2 were significantly higher, and the NF-κBp65 was significantly lower in the C8:0 and EPA groups (p < 0.05). Meanwhile, compared to the C8:0 group, the NF-κBp65 protein expression was significantly lower in the EPA group (p < 0.05). Our study showed that EPA had better effects than C8:0 on inhibiting inflammation and improving blood lipids in the absence of ABCA1. C8:0 may be involved mainly in inhibiting inflammation through upregulation of the ABCA1 and p-JAK2/p-STAT3 pathways, while EPA may be involved mainly in inhibiting inflammation through the TLR4/NF-κBp65 signaling pathway. The upregulation of the ABCA1 expression pathway by functional nutrients may provide research targets for the prevention and treatment of atherosclerosis.

Phenolipids are characteristic phytochemicals of Syzygium genus. However, the antidiabetic potential and underlying molecular mechanism of these components are not fully elucidated. Herein, we studied the anti-diabetic effects of jambone E (JE), a phenolipid from S. cumini, with in vitro and in vivo models. Data from current study showed that JE enhanced glucose consumption and uptake, promoted glycogen synthesis, and suppressed gluconeogenesis in insulin resistant (IR)-HepG2 cells and primary mouse hepatocytes. JE also attenuated streptozotocin-induced hyperglycemia and hyperlipidemia in type 1 diabetic (T1D) mice. Eleven metabolites (e.g. trimethylamine n-oxide, 4-pyridoxic acid, phosphatidylinositol 39:4, phenaceturic acid, and hippuric acid) were identified as potential serum biomarkers for JE's antidiabetic effects by an untargeted metabolomics approach. The further molecular mechanistic study revealed that JE up-regulated phosphorylation levels of protein kinase B (AKT), glycogen synthase kinase 3 beta, and forkhead box O1 (FoxO1), promoted nuclear exclusion of FoxO1 whilst decreased gene expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, phosphoenolpyruvate carboxykinase and glucose 6-phosphatase in IR-HepG2 cells and T1D mice. Our data suggested that JE might be a potent activator for AKT-mediated insulin signaling pathway, which was confirmed by the usage of AKT inhibitor and AKT-target siRNA interference, as well as the cellular thermal shift assay. Findings from the current study shed light on the anti-diabetic effects of phenolipids in the Syzygium species, which supports the use of medicinal plants in the Syzygium genus for potential pharmaceutical applications.

Guava is a popular fruit consumed worldwide with beneficial effects in regulation of glucose and lipid metabolism. Although polysaccharides are a major phytochemical component of guava, to date, the alleviative effects of polysaccharides from the guava fruit against diet-induced obesity remain unclear. The relationship between the anti-obesity effects of guava polysaccharide (GP) and gut microbiota is unknown. In current study, seven-week-old C57BL/6 mice were fed high-fat diet (HFD) supplemented with GP (100 mg/kg) by oral gavage for 11 weeks. GP supplementation alleviated HFD-induced body weight gain and visceral obesity, and reduced serum cholesterol, triglyceride, and LDL-C levels. In addition, GP ameliorated insulin resistance and prevented hepatic lipid accumulation and meta-inflammation in both liver and adipose tissues in obese mice. Remarkably, GP treatment restored the Firmicutes/Bacteroidetes ratio, induced growth of beneficial bacteria including Clostridium XlVa, Parvibacter, and Enterorhabdus, and decreased in inflammation-related bacteria Mucispirillum in mice fecal samples, accompanied with enhanced production of colonic short chain fatty acids especially butyric acid. However, the metabolic benefits of GP diminished in antibiotics-treated HFD-fed mice. Overall, GP improved metabolic profiles in HFD-induced obese mice via the mediation of gut microbiota-dependent pathways. GP might be developed and utilized as prebiotics in nutraceutical and food industry.

To explore the effects of Chinese raspberry (Fu-Pen-Zi) on diabetes, a polyphenol-enriched extract (FPZ) was prepared. Streptozotocin (STZ)-induced diabetic mice were daily administered FPZ (30 mg/kg body weight) for 18 days, the anti-diabetic effects were evaluated. Compared to STZ alone mice, FPZ-treatment ameliorated STZ-induced type 1 diabetes, reduced body weight loss (by 71.61%), hyperglycemia (fasting blood glucose reduced by 19.23%), hyperlipidemia (hepatic triglycerides reduced by 15.50%) and skeletal muscle atrophy (quadriceps mass increased by 21.46%). FPZ protected pancreatic β-cells from STZ-induced damage and promoted insulin secretion, preserved insulin signaling in liver tissues and skeletal muscles. FPZ improved glucose tolerance, modulated liver glycogen metabolism, and inhibited hepatic gluconeogenesis via activating insulin/Akt/Gsk3β and LKB1/AMPK signaling. Moreover, FPZ reduced liver oxidative stress and steatosis, reduced Atrogin-1 and Trim63 expression, contributes to muscle atrophy inhibition. This study highlights the potential usage of FPZ as nutritional interventions for type 1 diabetes and muscle atrophy management.

The chemical characteristics and hypolipidemic effects of alkylphenols in the fruit of Syzygium jambos were investigated in this study. Three cardanols (1-3; 1 as a new compound) and three alkylresorcinols (4-6) were isolated and identified from S. jambos fruit. Cardanols 1 and 2 (10-40 μM) suppressed lipids accumulation and reduced triglyceride content in oleic acid-overloaded HepG2 cells via the activation of AMPK/PPARα signaling pathways. Furthermore, the biological distribution of cardanols after an oral intake in mice was investigated. Compound 2 was detected in mice plasma, feces, and adipose tissues after a single oral intake (80 mg/kg body weight). In addition, an alkylphenols-enriched S. jambos fruit extract containing two bioactive compounds (95.9 and 198.6 μg/mg of compounds 1 and 2, respectively) was prepared. Findings from the current study highlight the potential usage of cardanols as well as S. jambos fruit for the management of dyslipidemia.

Clinacanthus nutans Lindau (Family: Acanthaceae) is a medicinal herb widely distributed in the tropic and subtropic areas of Asia. C. nutans is traditionally consumed as vegetable or herbal tea, as well as a folk medicine for anticancer and antifungal activities. However, to date, chemical constituent responsible for observed health beneficial effects of this medicinal plant is not clear. In the current study, 32 compounds (1−32), including three new megastigmanes (1–3) were isolated from the aerial parts of C. nutans. Their structures were elucidated on the basis of comprehensive NMR, MS, and CD spectroscopic data analysis, as well as chemical hydrolysis. Among the isolates, cycloartane triterpenoids (9, 10, and 12) displayed moderate anti-proliferative effects against HepG2 cell growth with IC50 values ranging from 9.12 to 19.89 μM. Data obtained from flow cytometry analysis and western blotting assays revealed that compounds 9 and 12 induced apoptosis of HepG2 cells by modulating the expression of proteins associated to mitochondrial-mediated apoptotic pathway. Furthermore, megastigmanes 1, 2, 7, and 8 enhanced the anti-Candida albicans activity of amphotericin B (AmB), supporting the synergistic effects between megastigmanes and AmB. This is the first report of anticancer and antifungal potential of cycloartane triterpenoids and megastigmanes in C. nutans, which shed useful insights on the relationship between C. nutans's chemical constituent and its beneficial effects to health. Findings from this study support further development of this medicinal plant for potential pharmaceutical applications.

Background Transmitted drug resistance (TDR) that affects the effectiveness of the first-line antiretroviral therapy (ART) regimen is becoming prevalent worldwide. However, its prevalence and transmission among HIV-1 treatment-naïve patients in Guangdong, China are rarely reported. We aimed to comprehensively analyze the prevalence of TDR and the transmission clusters of HIV-1 infected persons before ART in Guangdong. Methods The HIV-1 treatment-naïve patients were recruited between January 2018 and December 2018. The HIV-1 pol region was amplified by reverse transcriptional PCR and sequenced by sanger sequencing. Genotypes, surveillance drug resistance mutations (SDRMs) and TDR were analyzed. Genetic transmission clusters among patients were identified by pairwise Tamura-Nei 93 genetic distance, with a threshold of 0.015. Results A total of 2368 (97.17%) HIV-1 pol sequences were successfully amplified and sequenced from the enrolled 2437 patients. CRF07_BC (35.90%, 850/2368), CRF01_AE (35.56%, 842/2368) and CRF55_01B (10.30%, 244/2368) were the main HIV-1 genotypes circulating in Guangdong. Twenty-one SDRMs were identified among fifty-two drug-resistant sequences. The overall prevalence of TDR was 2.20% (52/2368). Among the 2368 patients who underwent sequencing, 8 (0.34%) had TDR to protease inhibitors (PIs), 22 (0.93%) to nucleoside reverse transcriptase inhibitors (NRTIs), and 23 (0.97%) to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Two (0.08%) sequences showed dual-class resistance to both NRTIs and NNRTIs, and no sequences showed triple-class resistance. A total of 1066 (45.02%) sequences were segregated into 194 clusters, ranging from 2 to 414 sequences. In total, 15 (28.85%) of patients with TDR were included in 9 clusters; one cluster contained two TDR sequences with the K103N mutation was observed. Conclusions There is high HIV-1 genetic heterogeneity among patients in Guangdong. Although the overall prevalence of TDR is low, it is still necessary to remain vigilant regarding some important SDRMs.

Background We launched a retrospective analysis of SARS-CoV-2 antibodies in 192 patients with COVID-19, aiming to depict the kinetic profile of SARS-CoV-2 antibodies and explore the factors related to SARS-CoV-2 antibody expression. Methods Data on 192 confirmed patients with COVID-19 between January and February 2020 was collected from the designated hospital that received patients with COVID-19 in Guangzhou, China. Moreover, a cohort of 130 suspected patients with COVID-19 and 209 healthy people were also enrolled in this study. IgM and IgG antibodies to SARS-CoV-2 were detected by the chemiluminescence immunoassay kits in different groups. Results A total of 192 COVID-19 cases were analyzed, of which had 81.8% anti-SARS-CoV-2 IgM detected and 93.2% anti-SARS-CoV-2 IgG detected, respectively, at the time of sampling. The kinetics of anti-SARS-CoV-2 IgM and IgG showed that, the confirmed cases had anti-SARS-CoV-2 IgM seroconversion occurred 5–10 days after the onset of the symptoms, and then IgM rose rapidly to reach a peak within around 2–3 weeks, maintaining at its peak for 1 week before its decline. While they had anti-SARS-CoV-2 IgG seroconversion simultaneously or sequentially with IgM, reaching its peak within around 3 to 4 weeks and began to decline after the fifth week. Besides, correlation analysis showed that in patients with COVID-19 the level of IgM was related to gender and disease severity (P Conclusion The findings of this study show that anti-SARS-CoV-2 IgM and IgG can be important assisting COVID-19 diagnosis, especially in the early phase of infection. Furthermore, antibody expression in patients with COVID-19 is also correlated with disease severity, age, gender, and virus clearance or continuous replication.

Novel core-shell-shell Fe@SiO 2 @(MnZn)Fe 2 O 4 soft magnetic composites (SMCs) with low core loss and high permeability were fabricated by a facile continuous chemical co-precipitation route and subsequent powder metallurgy technique. The typical double-shell structure for Fe@SiO 2 @(MnZn)Fe 2 O 4 powders was composed of a SiO 2 −(MnZn)Fe 2 O 4 mixed outer layer and an SiO 2 inner network embedded with trace amounts of (MnZn)Fe 2 O 4 . In comparison with Fe@SiO 2 SMCs, the Fe@SiO 2 @(MnZn)Fe 2 O 4 SMCs presented a notable flat high frequency characteristic up to 1 MHz, much higher permeability, and lower core loss which reduced with decreasing (MnZn)Fe 2 O 4 layer thickness. Fe@SiO 2 @(MnZn)Fe 2 O 4 SMCs prepared with 4 mL (MnZn)Fe 2 O 4 solution exhibited stable permeability of 64.0–63.5 up to 1 MHz and low core loss of 0.9–30.6 W/kg in 1–150 kHz. The strong magnetic coupling between the thin (MnZn)Fe 2 O 4 layer and Fe cores effectively reduced the air-gap thickness and demagnetization field giving rise to a high permeability. The low core loss could be attributed to the full separation of Fe core by thin dielectric−electrically insulating magnetic coupled with a SiO 2 /(MnZn)Fe 2 O 4 insulating layer. Our findings might shed insight on the design of novel SMCs with low core loss and high permeability.

Reactive oxygen species and subsequent oxidative stress are reported to play important roles in chronic metabolic diseases. Plant-derived polyphenols, especially food-derived phenolics, have attracted a lot of attention due to their potential usage against oxidative stress-related diseases. The leaf of Psidium guajava (known as guava) is regarded as a good resource of polyphenols and its products are commercially available in Japan as functional foods against multiple chronic metabolism disorders. In the course of finding novel polyphenols with antioxidative activities from guava leaf, 11 acylated phenolic glycosides (1-11), including 5 new oleuropeic acid-conjugated phenolic glycosides, named guajanosides A-E (1, 2, and 5-7), along with 17 known meroterpenoides (12-28), were isolated and identified. Their structures were determined by spectroscopic data analysis, chemical degradation, and acid hydrolysis. Compounds 1, 2, and 5-11 displayed potent reactive oxygen species-scavenging activity in lipopolysaccharide-stimulated RAW 264.7 macrophage cells. Western blot revealed that compound 6 markedly increased the expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone dehydrogenase 1 (NQO1), and the glutamate-cysteine ligase catalytic subunit. The current study revealed the presence of oleuropeic acid-derived phenolic glycosides in guava leaf and highlighted the potential usage of this type of phenolics against oxidative stress-related metabolic diseases via activation of the Nrf2 signaling pathway.

Extremely reduced oxygen (O2) levels are detrimental to myogenic differentiation and multinucleated myotube formation, and chronic exposure to high-altitude hypoxia has been reported to be an important factor in skeletal muscle atrophy. However, how chronic hypoxia causes muscle dysfunction remains unknown. In the present study, we found that severe hypoxia (1% O2) significantly inhibited the function of C2C12 cells (from a myoblast cell line). Importantly, the impairment was continuously manifested even during culture under normoxic conditions for several passages. Mechanistically, we revealed that histone deacetylases 9 (HDAC9), a member of the histone deacetylase family, was significantly increased in C2C12 cells under hypoxic conditions, thereby inhibiting intracellular autophagy levels by directly binding to the promoter regions of Atg7, Beclin1, and LC3. This phenomenon resulted in the sequential dephosphorylation of GSK3β and inactivation of the canonical Wnt pathway, impairing the function of the C2C12 cells. Taken together, our results suggest that hypoxia-induced myoblast dysfunction is due to aberrant epigenetic regulation of autophagy, and our experimental evidence reveals the possible molecular pathogenesis responsible for some muscle diseases caused by chronic hypoxia and suggests a potential therapeutic option.

In this paper, the global pinning synchronization problem of a class of complex dynamical networks with hybrid couplings, time delays, random data packet dropouts and multiple stochastic disturbances is investigated. The hybrid couplings are portrayed in three forms: constant couplings, discrete-delay couplings and distributed-delay couplings. The phenomenon of random packet dropouts is described as a binary random variable which obeys the Bernoulli distribution taking values of 0 and 1 with a certain probability. Multiple noisy processes herein are characterized by Brownian motions, which act on all coupling terms as well as the overall dynamics equation. By applying the Lyapunov method and stochastic analysis technique, sufficient conditions are established to ensure the considered stochastic delayed complex network to globally synchronize to a reference trajectory in the mean-square sense via the developed randomly occurring pinning control strategy. The obtained criteria are within the framework of linear matrix inequations. Finally, a simulation example is presented to verify the feasibility and effectiveness of the derived theoretical results.

Background Radiation exposure negatively affects the regenerative ability and makes reconstruction of bone defects after tumor section difficult. miR-34a is involved in radiation biology and bone metabolism. The aim of this study was to investigate whether miR-34a could contribute to bone regeneration in irradiated bone defects. Methods The expression of miR-34a was analyzed during the osteoblastic differentiation of irradiated BMSCs and bone formation in irradiated bone defects. miR-34a mimics and miR-34a inhibitor were used to upregulate or suppress the expression of miR-34a in BMSCs irradiated with 2 or 4 Gy X-ray radiation. In vitro osteogenesis and subcutaneous osteogenesis were used to assess the effects of miR-34a on the osteogenic ability of radiation-impaired BMSCs. Collagen-based hydrogel containing agomiR-34a or antagomiR-34a were placed into the 3-mm defects of irradiated rat tibias to test the effect of miR-34a on bone defect healing after irradiation. Results miR-34a was upregulated in the process of bone formation after irradiation. Transfecting radiation-impaired BMSCs with miR-34a mimics enhanced their osteoblastic differentiation in vitro by targeting NOTCH1. Overexpression of miR-34a enhanced the ectopic bone formation of irradiated BMSCs. In situ delivery of miR-34a promoted bone regeneration in irradiated bone defects. Conclusions miR-34a promoted the osteoblastic differentiation of BMSCs and enhanced the ectopic bone formation after irradiation. miR-34a promoted bone defect healing in irradiated rat tibias. miR-34a-targeted therapy might be a promising strategy for promoting the reconstruction of bone defects after radiotherapy. Electronic supplementary material The online version of this article (10.1186/s13287-019-1285-y) contains supplementary material, which is available to authorized users.

Objectives The aim of this study was to evaluate the reliability and validity of the Chinese version of the Stigma Scale for Chronic Illness (SSCI) in patients with stroke. Methods In total, 220 patients with stroke were recruited to complete the scale. The reliability of the SSCI was evaluated using internal consistency and test-retest methods. Exploratory factor analysis (EFA) was conducted to identify domains of the SSCI. Convergent validity was determined by analyzing the correlation between SSCI scores, activities of daily living (ADL) and depression. Results Construct validity was determined by factor analysis, extracting three factors with eigenvalues greater than 1, explaining 30.5%, 25.7%, and 8.5% of the variance, respectively, and accounting for 64.8% of the variance. All items had factor loadings above 0.40. The first factor comprised questions related to 'self-stigma' (items 1-13). The second (items 14-22) and third (items 23-24) factors aggregated questions related to 'enacted stigma'. In terms of convergent validity, the SSCI total scale was moderately correlated to the Barthel Index (BI) and the Self-rating Depression Scale (SDS). Cronbach's alpha value (internal reliability) for the total SSCI score was 0.949, and the intraclass correlation coefficient value (test-retest reliability) was 0.802. Discussion The results provide initial evidence that the SSCI is a reliable and validated measure for evaluating stigma in stroke patients in China.

Novel core@shell@shell structured carbonyl iron powder (CIP)@SiO2@ Mn0.6Zn0.4Fe2O4 ferrite composites having great microwave absorption characteristics were successfully synthesized using chemical co-precipitation. The microstructure, morphology and microwave absorption performance of CIP@SiO2@Mn0.6Zn0.4Fe2O4 ferrite composites were systematically investigated. The results show that both coating layers of SiO2 and Mn0.6Zn0.4Fe2O4 are uniform and fine. The prepared CIP@SiO2@Mn0.6Zn0.4Fe2O4 composites in this study display better dielectric loss and frequency characteristic at high frequency than CIP, CIP@SiO2 and CIP@Mn0.6Zn0.4Fe2O4. The results of electromagnetic parameters also indicate that the enhanced microwave absorption performance primarily originates from the substantial contributions of magnetic loss to reflection loss. The optimal value of reflection loss of CIP@SiO2@Mn0.6Zn0.4Fe2O4 having the thickness of 2 mm can reach up to −44.24 dB at 11.57 GHz as well as the bandwidth (RL ≤ −10 dB) from 9.04 to 16.16 GHz among the frequency range from 2 to 18 GHz. In addition, the greatly enhanced microwave absorption performance is attributed to good wave impedance matching, high attenuation constant, multi-relaxation processes and multiple interfacial polarization.

A numerical correction algorithm (NCA) is proposed to improve the accuracy of atmospheric temperature profile in clear and cloudy days based on the weighting functions of different frequencies. The weighting functions of atmospheric brightness temperatures (BTs) with respect to temperature profiles are analyzed in detail. A performance assessment of the microwave radiometer (MWR) MP-3000A is operated with the observations from March to August 2018 in Harbin China (126.40∘E 45.46∘N). And a numerical method is used to calculate weighting functions with the downwelling monochromatic radiative transfer model (MonoRTM). According to the weighting functions, a cost function is defined in NCA to minimize the biases between the measured and calculated BTs by correcting the measured temperature profiles. A simulation is designed to examine the NCA based on the methodology and data. The experimental results show that the NCA can adjust the temperature profiles below 5 km. However, there is almost no improvement above 5 km because of the attenuation of radiation. And the statistic results show that the RMSE and MAE of temperature profiles corrected with NCA are reduced by 12.5% and 17.9% when compared with the uncorrected observations. Especially, both of the RMSE and MAE of the temperature profiles below 2 km are reduced by more than 50%.

In this paper, the problem of containment control is investigated for a class of multi-agent systems with second-order integrator dynamics. A directed graph is considered, and a pair of matrix norm and vector norm is designed. Accounting for the limitation of the finite bandwidth channels, quantized communication topology based on the encoding–decoding strategy is designed, in which the quantizers only have finite quantization levels and it is independent of the initial state of agents. Moreover, the quantizer and controller are jointly designed only using the estimated value of the neighbors’ state information to ensure the system stability with less communication resource. The relationship between the quantization levels and sampling interval is established to guarantee that all the quantizers are not saturated, and thus ensure the asymptotic stability of the system. And a vector norm induced by a constructed matrix norm is applied to reduce the lower boundary of the communication data rate which is free from the dimension and number of agents. Finally, simulation examples are given to show the effectiveness of the new designed techniques.

Four subsurface flow constructed wetlands (SFCWs) filled with different substrates including ceramsite, ceramsite + pyrite, ceramsite + ferrous sulfide, and ceramsite + pyrite + ferrous sulfide (labeled as SFCW-S1, SFCW-S2, SFCW-S3, and SFCW-S4) were constructed, and the removal of nitrogen and phosphorus by these SFCWs coupled with intermittent aeration in the front section was discussed. The key findings from different substrate analyses, including nitrification and denitrification rate, enzyme activity, microbial community structure, and the X-ray diffraction, revealed the nitrogen and phosphorus removal mechanism. The results showed that the nitrogen and phosphorus removal efficiency for SFCW-S1 always remains the lowest, and the phosphorus removal efficiency for SFCW-S4 is recorded as the highest one. However, after controlling the dissolved oxygen by intermittent aeration in the front section of SFCWs, the nitrogen and phosphorus removal efficiencies of SFCWs-S2 and S4 becomes higher than those of SFCW-S1, and SFCW-S3. It was noticed that the pollutants were removed mainly in the front section of the SFCWs. Both precipitation and adsorption on the substrate were the main mechanisms for phosphorus removal. A minute difference of nitrification rate and ammonia monooxygenase activity was observed in the SFCWs aeration zone. The denitrification rates, nitrate reductase, nitrite reductase, and electron transport system activity for SFCW-S2 and SFCW-S4 were higher than those detected for SFCW-S1 and SFCW-S3 in the non-aerated zone. Proteobacteria was the largest phyla found in the SFCWs. Moreover, Thiobacillus occupied a large proportion found in SFCW-S2, and SFCW-S4, and it played a crucial role in pyrite-driven autotrophic denitrification.

BACKGROUND The aim of this study was to assess the interaction between thyroid malignancies and thyroid anterior capsule by ultrasound quantification to determine extra-capsular invasion. MATERIAL AND METHODS A total of 145 patients preoperatively diagnosed with malignant nodules under the thyroid anterior capsule were selected and routinely examined by ultrasound. The length of the nodules (from the junction of the nodule capsule to the deepest point of the nodule, vertical diameter, V) and the distance between the nodule protruding from thyroid capsule and the highest protruding (ledge length, L) nodule were used to obtain the L/V ratio. These parameters where then used to compare the efficacy of predicting extra-thyroid extension (ETE) between L/V, the aspect ratio of the tumor, and manual judgment. RESULTS Out of 145 nodules, there were 63 ETEs and 82 non-ETEs determined by ultrasound. Extra-capsular invasion was associated with L//V ratio, but there was no significant correlation between capsular invasion and AR (aspect ratio), age, location, or presence of clustered calcification. The ability of the ratio of L/V to predict extra-capsular invasion was superior to the predictive ability of the AR ratio. With a Youden index of 0.593, the L/V ratio was 0.2325. The use of the L/V ratio to determine the presence of ETE was superior to subjective visual judgment. CONCLUSIONS The calculation of L/V ratio by ultrasound could more precisely predict the ETE compared with manual judgment, which indirectly reflects the interaction between thyroid capsule and malignant nodules. The above conclusions need to be confirmed by a range of cases.

Four subsurface flow constructed wetlands (SFCWs) filled with different substrates including ceramsite, ceramsite+pyrite, ceramsite+ferrous sulfide, and ceramsite+pyrite+ferrous sulfide (labeled as SFCW-S1, SFCW-S2, SFCW-S3, and SFCW-S4) were constructed, and the removal of nitrogen and phosphorus by these SFCWs coupled with intermittent aeration in the front section was discussed. The key findings from different substrate analyses, including nitrification and denitrification rate, enzyme activity, microbial community structure, and the X-ray diffraction, revealed the nitrogen and phosphorus removal mechanism. The results showed that the nitrogen and phosphorus removal efficiency for SFCW-S1 always remained the lowest, and the phosphorus removal efficiency for SFCW-S4 was recorded as the highest one. However, after controlling the dissolved oxygen by intermittent aeration in the front section of SFCWs, the nitrogen and phosphorus removal efficiencies of SFCWs-S2 and S4 became higher than those of SFCW-S1, and SFCW-S3. It was noticed that the pollutants were removed mainly in the front section of the SFCWs. Both precipitation and adsorption on the substrate were the main mechanisms for phosphorus removal. A minute difference of nitrification rate and ammonia monooxygenase activity was observed in the SFCWs' aeration zone. The denitrification rates, nitrate reductase, nitrite reductase, and electron transport system activity for SFCW-S2 and SFCW-S4 were higher than those detected for SFCW-S1 and SFCW-S3 in the non-aerated zone. Proteobacteria was the largest phyla found in the SFCWs. Moreover, Thiobacillus occupied a large proportion found in SFCW-S2, and SFCW-S4, and it played a crucial role in pyrite-driven autotrophic denitrification.

Dual therapy with lopinavir/ritonavir (LPV/r) plus lamivudine (3TC) has been demonstrated to be non-inferior to the triple drug regimen including LPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) in 48-week studies. However, little is known about the long-term efficacy and drug resistance of this simplified strategy. A randomized, controlled, open-label, non-inferiority trial (ALTERLL) was conducted to assess the efficacy, drug resistance, and safety of dual therapy with LPV/r plus 3TC (DT group), compared with the first-line triple-therapy regimen containing tenofovir (TDF), 3TC plus efavirenz (EFV) (TT group) in antiretroviral therapy (ART)-naïve HIV-1–infected adults in Guangdong, China. The primary endpoint was the proportion of patients with plasma HIV-1 RNA < 50 copies/ml at week 144. Between March 1 and December 31, 2015, a total of 196 patients (from 274 patients screened) were included and randomly assigned to either the DT group (n = 99) or the TT group (n = 97). In the primary intention-to-treat (ITT) analysis at week 144, 95 patients (96%) in the DT group and 93 patients (95.9%) in the TT group achieved virological inhibition with plasma HIV-1 RNA + cell count (247.0 vs. 204.5 cells/mm3; p = 0.074) or the CD4/CD8 ratio (0.47 vs. 0.49; p = 0.947) from baseline, or the inflammatory biomarker levels through week 144 compared with the TT group. For the subgroup analysis, baseline high viremia (HIV-1 RNA > 100,000 copies/ml) and genotype BC did not affect the primary endpoint or the mean increase in CD4+ cell count or CD4/CD8 ratio from baseline at week 144. However, in patients with genotype AE, the DT group showed a higher mean increase in CD4+ cell count from baseline through 144 weeks than the TT group (308.7 vs. 209.4 cells/mm3; p = 0.038). No secondary HIV resistance was observed in either group. Moreover, no severe adverse event (SAE) or death was observed in any group. Nonetheless, more patients in the TT group (6.1%) discontinued the assigned regimen than those in the DT group (1%) due to adverse events. Dual therapy with LPV/r plus 3TC manifests long-term non-inferior therapeutic efficacy, low drug resistance, good safety, and tolerability compared with the first-line triple-therapy regimen in Guangdong, China, indicating dual therapy is a viable alternative in resource-limited areas.Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR1900024611].

Host immune response and viral factors are involved in disease progression in patients with chronic hepatitis B virus (HBV) infection. However, the relationship between HBV quasispecies and liver fibrosis progression remains unclear. In this study, 447 patients with chronic HBV infection, including 239 with chronic hepatitis B (CHB), 104 with liver cirrhosis (LC) and 104 with hepatocellular carcinoma (HCC) were enrolled. The 239 CHB patients were divided into groups F1, F2, and F3 according to liver fibrosis score. Four fragments of the HBV genome were determined and analyzed using next-generation sequencing. Specific mutations, such as A1762T, G1764A and G1896A, in the BCP/PC region were more common in patients with advanced liver disease and formed the majority of the viral quasispecies pool in patients with LC and HCC. The viral complexity and diversity increased as the fibrosis progressed, especially in patients with CHB who were comparable in age but at different stages of fibrosis. Patients with early-stage fibrosis experienced higher purifying selection pressure in the four sequenced regions, whereas different protein-coding region experienced different negative selection with disease progression. HBV quasispecies diversity may increase fibrosis progression in CHB patients with aging under immune selection.