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Background To investigate the influence of diabetes duration and glycemic control, assessed by glycated hemoglobin (HbA1c) levels, on risk of incident dementia. Methods The present study is a prospective study of 461 563 participants from the UK Biobank. The age at diabetes diagnosis was determined by self-report. Diabetes duration was calculated as baseline age minus age at diagnosis. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidential intervals (CIs). Results During a median follow-up of 8.1 years, 2 233 dementia cases were recorded. As compared with normoglycemic individuals, individuals with diabetes had higher risk of all-cause dementia, and the risk increased with increasing duration of diabetes; compared with participants with diabetes duration of Conclusions Diabetes duration appeared to be associated with the risk of incident dementia due to factors beyond glycemic control. Clinicians should consider not only glycemic control but also diabetes duration in dementia risk assessments for patients with diabetes.

Background: Wealth and income are potential modifiable risk factors for dementia, but whether wealth status, which is composed of a combination of debt and poverty, and assessed by wealth and income, is associated with cognitive impairment among elderly adults remains unknown. Objective: To examine the associations of different combinations of debt and poverty with the incidence of dementia and cognitive impairment without dementia (CIND) and to evaluate the mediating role of depression in these relationships. Methods: We included 15,565 participants aged 51 years or older from the Health and Retirement Study (1992–2012) who were free of CIND and dementia at baseline. Dementia and CIND were assessed using either the modified Telephone Interview for Cognitive Status (mTICS) or a proxy assessment. Cox models with time-dependent covariates and mediation analysis were used. Results: During a median of 14.4 years of follow-up, 4,484 participants experienced CIND and 1,774 were diagnosed with dementia. Both debt and poverty were independently associated with increased dementia and CIND risks, and the risks were augmented when both debt and poverty were present together (the hazard ratios [95% confidence intervals] were 1.35 [1.08–1.70] and 1.96 [1.48–2.60] for CIND and dementia, respectively). The associations between different wealth statuses and cognition were partially (mediation ratio range: 11.8–29.7%) mediated by depression. Conclusion: Debt and poverty were associated with an increased risk of dementia and CIND, and these associations were partially mediated by depression. Alleviating poverty and debt may be effective for improving mental health and therefore curbing the risk of cognitive impairment and dementia.

Streptomycetes possess numerous gene clusters and the potential to produce large amounts of natural products. Histone deacetylase (HDAC) inhibitors play an important role in the regulation of histone modifications in fungi, but little is known about the roles of HDAC in prokaryotes. Here, we described the global effects of the HDAC inhibitor, sodium butyrate (SB), on marine-derived Streptomyces olivaceus FXJ 8.021, particularly on the activation of secondary metabolites biosynthesis. antiSMASH analysis revealed 33 secondary metabolite biosynthetic gene clusters (BGCs) in strain FXJ 8.021, among which the silent lobophorin BGC was activated by SB. Transcriptomic data showed that the expression of genes involved in lobophorin biosynthesis (ge00097-ge00139) and CoA-ester formation (e.g., ge02824), as well as glycolysis/gluconeogenesis pathway (e.g., ge01661), was mainly up-regulated in the presence of SB. Intracellular CoA-ester analysis confirmed that SB triggered the biosynthesis of CoA-ester, increasing the precursor supply for lobophorin biosynthesis. Further acetylome analysis revealed that the acetylation levels on 218 acetylation sites of 190 proteins were up-regulated and those on 411 sites of 310 proteins were down-regulated. These acetylated proteins were particularly enriched in transcriptional and translational machinery components (e.g., elongation factor GE04399), and their correlations with the proteins involved in lobophorin biosynthesis were established by protein-protein interaction network analysis, suggesting that SB might function via a complex hierarchical regulation to activate expression of lobophorin BGC. These findings provide solid evidence that acetylated proteins triggered by SB could affect the expression of genes in the biosynthesis of primary and secondary metabolites in prokaryotes.

AIMS To assess the associations of diabetes duration and glycaemic control (defined by plasma glycated haemoglobin [HbA1c] level) with the risks of cardiovascular disease (CVD) and all-cause mortality and to determine whether the addition of either or both to the established CVD risk factors can improve predictions. MATERIALS AND METHODS A total of 435 679 participants from the UK Biobank without CVD at baseline were included. Cox models adjusting for classic risk factors (sociodemographic and anthropometric characteristics, lipid profiles and medication use) were used, and predictive utility was determined by the C-index and net reclassification improvement (NRI). RESULTS Compared with participants without diabetes, participants with longer diabetes durations and poorer glycaemic control had a higher risk of fatal/nonfatal CVD. Among participants with diabetes, the fully-adjusted hazard ratios (HRs) for diabetes durations of 5 to

Background Risk for transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to close contacts of infected persons has not been well estimated. Objective To evaluate the risk for transmission of SARS-CoV-2 to close contacts in different settings. Design Prospective cohort study. Setting Close contacts of persons infected with SARS-CoV-2 in Guangzhou, China. Participants 3410 close contacts of 391 index cases were traced between 13 January and 6 March 2020. Data on the setting of the exposure, reverse transcriptase polymerase chain reaction testing, and clinical characteristics of index and secondary cases were collected. Measurement Coronavirus disease 2019 (COVID-19) cases were confirmed by guidelines issued by China. Secondary attack rates in different settings were calculated. Results Among 3410 close contacts, 127 (3.7% [95% CI, 3.1% to 4.4%]) were secondarily infected. Of these 127 persons, 8 (6.3% [CI, 2.1% to 10.5%]) were asymptomatic. Of the 119 symptomatic cases, 20 (16.8%) were defined as mild, 87 (73.1%) as moderate, and 12 (10.1%) as severe or critical. Compared with the household setting (10.3%), the secondary attack rate was lower for exposures in health care settings (1.0%; odds ratio [OR], 0.09 [CI, 0.04 to 0.20]) and on public transportation (0.1%; OR, 0.01 [CI, 0.00 to 0.08]). The secondary attack rate increased with the severity of index cases, from 0.3% (CI, 0.0% to 1.0%) for asymptomatic to 3.3% (CI, 1.8% to 4.8%) for mild, 5.6% (CI, 4.4% to 6.8%) for moderate, and 6.2% (CI, 3.2% to 9.1%) for severe or critical cases. Index cases with expectoration were associated with higher risk for secondary infection (13.6% vs. 3.0% for index cases without expectoration; OR, 4.81 [CI, 3.35 to 6.93]). Limitation There was potential recall bias regarding symptom onset among patients with COVID-19, and the symptoms and severity of index cases were not assessed at the time of exposure to contacts. Conclusion Household contact was the main setting for transmission of SARS-CoV-2, and the risk for transmission of SARS-CoV-2 among close contacts increased with the severity of index cases. Primary funding source Guangdong Province Higher Vocational Colleges and Schools Pearl River Scholar Funded Scheme.

Neomycin, a multicomponent aminoglycoside antibiotic, is mainly utilized in livestock husbandry and feed additives in animals. The antimicrobial potency of the main product neomycin B is higher than that of its stereoisomer neomycin C. However, the content of neomycin C as an impurity in the high-producing strain is relatively high, and its isolation or removal from neomycin B is quite difficult, which influences the widespread application of neomycin. In this work, the essential genes responsible for neomycin biosynthesis were evaluated and overexpressed to reduce the content of neomycin C. Among them, neoG and neoH are two novel regulatory genes for neomycin biosynthesis, aphA is a resistance gene, neoN encoding a radical SAM-dependent epimerase is responsible for the conversion of neomycin C to B using SAM as the cofactor, and metK is a SAM synthetase coding gene. We demonstrated that the reconstitution and overexpression of a mini-gene-cluster (PkasO*-neoN-metK-PkasO*-neoGH-aphA) could effectively reduce the accumulation of neomycin C from 19.1 to 12.7% and simultaneously increase neomycin B by ∼13.1% in the engineered strain Sf/pKCZ04 compared with the wild-type strain (Sf). Real-time quantitative polymerase chain reaction analysis revealed the remarkable up-regulation of the neoE, neoH, neoN, and metK genes situated in the mini-gene-cluster. The findings will pave a new path for component optimization and the large-scale industrial production of significant commercial antibiotics.

Emerging evidence indicates that hyperglycemia has an adverse impact on the knee joint which, in turn, may increase the risk of knee osteoarthritis (OA), but evidence from the real-life settings of large-scale cohort studies remains unclear. We sought to evaluate the association of glycemic control and the risk of symptomatic knee OA in a community-based cohort of older adults.We conducted a prospective analysis of 10,730 participants without knee OA. Comprehensive blood biomarker data were obtained. Diabetes mellitus (DM) was defined mainly using a glycosylated hemoglobin (HbADuring a median follow-up of 5 years, knee OA developed in 1,089 participants (108 with DM and 971 without). Knee OA was related to DM (hazard ratio [HR] 1.29 [95% confidence interval (95% CI) 1.02-1.78]), bad glycemic regulation in DM patients (HR 1.41 [95% CI 1.05-2.09]), and long-term DM (≥5 versus5 years; HR 1.49 [95% CI 1.02-2.17]). High levels of HbADM, bad glycemic management, and long-term DM are potential risk factors of symptomatic knee OA independent of age and body mass index. Targeting blood glucose, in addition to bodyweight, may be an important avenue for prevention of knee OA.

The relationship between body mass index (BMI) and cognitive impairment remains controversial, especially in older people. This study aims to confirm the association of phenotypic and genetic obesity with cognitive impairment and the benefits of adhering to a healthy lifestyle. This prospective study included 10,798 participants (aged ≥ 50 years) with normal cognitive function from the Health and Retirement Study in the United States. Participants were divided into low (lowest quintile), intermediate (quintiles 2–4), and high (highest quintile) groups according to their polygenic risk score (PRS) for BMI. The risk of cognitive impairment was estimated using Cox proportional hazard models. Higher PRS for BMI was associated with an increased risk, whereas phenotypic obesity was related to a decreased risk of cognitive impairment. Never smoking, moderate drinking, and active physical activity were considered favourable and associated with a lower risk of cognitive impairment compared with current smoking, never drinking, and inactive, respectively. A favourable lifestyle was associated with a low risk of cognitive impairment, even in subjects with low BMI and high PRS for BMI. This study suggest that regardless of obesity status, including phenotypic and genetic, adhering to a favourable lifestyle is beneficial to cognitive function.

BackgroundThe prevalence of diabetes is on the rise globally coupled with its associated complications, such as diabetic nephropathy (DN). Obesity has been identified as a risk factor for the development of DN but it is still unclear which obesity index is the best predictor of incident DN.MethodsData from the participants with type 2 diabetes mellitus (T2DM) in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study were used to examine the sex-specific association between waist circumference (WC), waist-to-height ratio (WHtR), and body mass index (BMI) with incident DN risk.ResultsAmong the 8,887 participants with T2DM (5,489 men and 3,398 women), 5,296 participants (3,345 men and 1,951 women) developed the DN composite outcome during a follow-up period of 24302 person-years. Among men, null associations were observed between all anthropometric measures with incident DN in the multivariate analysis although the 3rd quartile of WHtR showed marginally significant results (P = 0.052). However, among women, both central and general obesity measures were associated with increased risks of incident DN. Compared with participants in the WC nd to the 4th quartile of WHtR were 1.09 (95% CI 0.96-1.25), 1.12 (95% CI 0.98-1.28), and 1.14 (95% CI 1.00-1.30) respectively; also, compared with the normal BMI category, the fully adjusted HRs and 95% CIs for class I – class III obese were 1.36 (95% CI 1.10 – 1.67), 1.43 (95% CI 1.16 – 1.78) and 1.32 (95% CI 1.05 – 1.66) respectively.ConclusionsAmong participants with T2DM, higher levels of both central and general obesity indexes were associated with DN risk among women but not in men. Women with T2DM should maintain a healthy weight targeted at reducing both central and general obesity to enhance nephroprotection. Trial registration: ClinicalTrials.gov., no. NCT00000620.

Background As magnetic resonance angiography (MRA) has been increasingly used in the follow-up of intracranial aneurysms (IAs) as a non-invasive technique, the knowledge framework and areas of research interest in intracranial aneurysms magnetic resonance angiography (IAMRA) change approximately every 10 years. However, few studies have quantitatively analyzed the published literature in this field. In the present study, we used scientometrics to survey the knowledge field, development trends, and research focus of IAMRA with the aim of providing a reference for further study. Methods We collected articles on IAMRA published from 2004 (Jan 1, 2004) to 2020 (May 24, 2020). Web of Science Core Collection databases (WoSCCd) including the Science Citation Index Expanded were searched. An experienced staff member from the Department of Radiology at Southern Medical University, assisted in screening articles for relevant articles. We used ArcGIS (a mapping and location analytics platform) to perform geographic visualization. Excel 2016 was used to analyze the literature data, including number of publications, impact factor (IF), and publication year. CiteSpace V was used to conduct a series of literature feature clustering, including author co-citation analysis, reference co-citation analysis (RCA), and burst keywords analysis. Results A total of 1,272 articles on IAMRA published between 2004 and 2020 were included. Of 257 journals, American Journal of Neuroradiology (IF 2018: 3.256) published the most IAMRA articles (109 publications, 8.57%), followed by Journal of Neurosurgery (IF 2018: 4.131, 51 publications, 4.16%), and Neuroradiology (IF 2018: 2.504, 51 publications, 4.01%). Of 56 countries, the USA published the most, with 347 articles [27.28%, IF: 3.14 (average IF of all journals in the country)], followed by Japan (242 articles, 19.03%, IF: 2.38), Germany (135 articles, 10.61%, IF: 3.21), and China (101 articles, 7.94%, IF: 2.86). A total of 1387 institutions published articles, with the Mayo Clinic publishing the most (33 articles, 2.59%), followed by Shanghai Jiao Tong University (25 article, 1.97%), Seoul National University (23 articles, 1.81%), and University Medical Center Utrecht (19 articles, 1.49%). Of 399 authors, Rinkel ranked first with 19 articles, followed by Li MH (18 articles), Uchino A (15 articles), and Saito N (13 articles). Cluster RCA showed that the first cluster was "#0 growth", followed by "#1 Guglielmi detachable coils". Timeline views showed that the time span of "#0 growth" was the closest to today. The modularity value was 0.6971, and the mean silhouette value was 0.5477. According to the burst keyword analysis, "risk factors associated to rupture" was the topic with the strongest burst since 2017. Studies conducted in several countries suggested that age is inversely related to the risk of rupture, which implies the importance of MRA follow-up for patients of different age. Conclusions From 2004 to 2020, the number of published IAMRA-related articles gradually increased. The USA and Western Europe lead in the field, with a concentration of cutting-edge talents and high-level scientific research institutions. A synthesis of the clustering results of RCA and burst keyword analysis indicated that unruptured IA growth, stent-assisted coil embolization, and risk factors associated to rupture were the current hotspots in IAMRA research.

Background Higher fluctuation of cholesterol has been shown associated with cognitive decline. But the association between unidirectional variation of cholesterol and cognition remains unclear. In the present study, we examined the association between variation of cholesterol from normal to high level or from high to normal level and cognition. Methods A total of 4,915 participants (mean age, 57.7 years; 49.2% female) with normal cognition in baseline (2011) from the China Health and Retirement Longitudinal Study (CHARLS) were included. Plasma total cholesterol (TC), non-high-density lipoprotein cholesterol (NHDL-C), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were divided into two clusters according to cutoff in 2011 and 2015, respectively. Participants were divided into four groups: normal-normal, normal-high, high-normal and high-high. Cognitive functions were assessed by episodic memory and mental intactness. The binary logistic regression was used to analyze the association of cholesterol variation with cognitive decline. Results Participants with increased cholesterol were more likely had lower incidence of cognitive decline. The fluctuations of cholesterol were more likely occurred in females. The odds ratio (OR) and 95% confidence interval (CI) of global cognitive decline in normal-high compared with normal-normal group of TC was 0.61 (0.36–1.03), and significant only in females [OR and 95% CI: 0.50 (0.26–0.97)]; the risk of memory function decline in high-normal group compared with high-high group was increased both in males [OR and 95% CI: 1.98 (1.02–4.05)] and females [OR and 95% CI: 1.61 (1.01–2.74)]. The similarly results were shown in NHDL-C groups [OR and 95% CI of global cognitive decline in normal-high group: 0.50 (0.26–0.95) for overall; 0.38 (0.17–0.85) for females]; but the risk of memory function decline in high-normal group only increased in females [OR and 95% CI: 1.64 (1.02–2.25)]. The risk of mental intactness decline in males significantly decreased in high-normal group of LDL-C compared with high-high group [OR and 95% CI: 0.30 (0.13–0.67)] and increased in high-high compared with normal-normal group [OR and 95% CI: 2.27 (1.18–2.98)]. Conclusions Longitudinal decreasing of TC or NHDL-C is detrimental to cognitive function, especially in females. But LDL-C is still a risk factor of cognitive decline in males.

Introduction The relationship between variability in cardiometabolic and inflammatory parameters and cognitive changes is unknown. This study investigates the association of visit-to-visit variability in BMI, mean arterial pressure, total cholesterol, triglycerides, HbA1c, high-sensitivity C-reactive protein, ferritin, and fibrinogen with cognitive decline. Methods This population-based cohort study included 2,260 individuals (mean age=63.0 [SD=7.5] years) free of cognitive diseases who underwent ≥3 clinical measurements from 2004 to 2019. Variability was expressed as variability independent of the mean across visits. Participants were divided on the basis of quartiles of variability score, a scoring system generated to explore the composite effect of parameter variability (range=0−24), where 0 points were assigned for Quartile 1, 1 point was assigned for Quartile 2, 2 points were assigned for Quartile 3, and 3 points were assigned for Quartile 4, each for the variability of 8 parameters measured as variability independent of the mean. Linear mixed models evaluated the longitudinal associations with cognitive decline in memory and verbal fluency. All analyses were conducted in 2020−2021. Results Higher BMI, mean arterial pressure, total cholesterol, HbA1c, and ferritin variability were linearly associated with cognitive decline irrespective of their mean values. In addition, participants in the highest quartile of variability score had a significantly worse cognitive decline rate in memory (−0.0224 points/year, 95% CI= −0.0319, −0.0129) and verbal fluency (−0.0088 points/year, 95% CI= −0.0168, −0.0008) than those in the lowest quartile. Conclusions A higher variability in cardiometabolic and inflammatory parameters was significantly associated with cognitive decline. Stabilizing these parameters may serve as a target to preserve cognitive functioning.

Neomycin, a multicomponent aminoglycoside antibiotic, is mainly utilized in livestock husbandry and feed additives in animals. The antimicrobial potency of the main product neomycin B is higher than that of its stereoisomer neomycin C. However, the content of neomycin C as an impurity in the high-producing strain is relatively high, and its isolation or removal from neomycin B is quite difficult, which influences the widespread application of neomycin. In this work, the essential genes responsible for neomycin biosynthesis were evaluated and overexpressed to reduce the content of neomycin C. Among them

The phenomenon of COVID-19 patients tested positive for SARS-CoV-2 after discharge (redetectable as positive, RP) emerged globally. The data of incidence rate and risk factors for RP event and the clinical features of RP patients may provide recommendations for virus containment and cases management for COVID-19. We prospectively collected and analyzed the epidemiological, clinical and virological data from 285 adult patients with COVID-19 and acquired their definite clinical outcome (getting PCR positive or not during post-discharge surveillance). By March 10, 27 (9.5%) discharged patients had tested positive for SARS-CoV-2 in their nasopharyngeal swab after a median duration of 7·0 days (IQR 5·0–8·0). Compared to first admission, RP patients generally had milder clinical symptoms, lower viral load, shorter length of stay and improved pulmonary conditions at readmission (p0.05). A prolonged duration of viral shedding (>10 days) during the first hospitalization [adjusted odds ratio [aOR]: 5.82, 95% confidence interval [CI]: 2.50–13.57 for N gene; aOR: 9.64, 95% CI: 3.91–23.73 for ORF gene] and higher Ct value (ORF) in the third week of the first hospitalization (aOR: 0.69; 95% CI: 0.50–0.95) were associated with RP events. In conclusion, RP events occurred in nearly 10% of COVID-19 patients shortly after the negative tests, were not associated with worsening symptoms and unlikely reflect reinfection. Patients’ lack of efficiency in virus clearance was a risk factor for RP result. It is noteworthy that elder RP patients (≥ 60 years old) were more susceptible to clinical symptoms at readmission., Author summary The baseline enrolled 285 patients admitted to Guangzhou Eighth People’s Hospital (Guangzhou, Guangdong) with a diagnosis of COVID-19. We reported the epidemiology, clinical laboratory, radiological characteristics, virological results, treatment, and definite outcomes (getting PCR retested positive (RP) or not during post-discharge surveillance) of the cases. RP events occurred in nearly 10% of cases, were not associated with worsening symptoms and unlikely reflect reinfection. The lack of efficiency in virus clearance was a risk factor for RP result. Elder RP patients (≥ 60 years old) were more susceptible to clinical symptom at readmission. In the context of numerous COVID-19 cases showed SARS-CoV-2 positive again after discharged, the data in China may provide recommendations for post-discharge management, especially for other developing countries.

Background: The Northern Hemisphere faces the prospect of the coronavirus disease 2019 (COVID-19) pandemic and a simultaneous epidemic of seasonal influenza. However, the clinical impacts of single and dual infections with influenza A (H1N1) and SARS-CoV-2 haven’t been well described. Objectives: We aim to compare the clinical features, severity and outcome among patients with single and dual infections with influenza A (H1N1) and SARS-CoV-2. Methods: Characteristics and outcomes in adults (≥18 years) hospitalized for H1N1 infection (n = 220) were retrospectively compared with cases hospitalized for SARS-CoV-2 infection (n = 249) and co-infection with both viruses (n = 36) in a single-center study in Guangzhou, China. Results: Compared with COVID-19 infection, patients with H1N1 were more likely to have clinical symptoms (P 20 d), pneumonia, secondary bacterial infections and admittance to ICU, compared with H1N1 patients (P < 0.05). Conclusion: COVID-19 patients have a higher incidence of pneumonia during hospitalization whilst fewer onset symptoms than H1N1 patients. Co-infection was more found in older age and was associated with poorer clinical outcomes.

Data are limited on the viral load, viral shedding patterns, and potential infectivity of asymptomatic patients (APs) with coronavirus disease 2019 (COVID-19). This study included 31 adult patients who were virologically confirmed to have COVID-19 but were asymptomatic on admission. Among these 31 patients, 22 presented symptoms after admission and were defined as asymptomatic patients in the incubation period (APIs); the other nine patients remained asymptomatic during hospitalization and were defined as asymptomatic patients (APs). The median cycle threshold (Ct) value of APs (39.0, interquartile range (IQR) 37.5-39.5) was significantly higher than that of APIs (34.5, IQR 32.2-37.0), indicating a lower viral load in APs. However, the duration of viral shedding remained similar in the two groups (7 days, IQR 5-14 days vs. 8 days, IQR 5-16 days). The study findings demonstrated that although APs with COVID-19 have a lower viral load, they still have certain period of viral shedding, which suggests the possibility of transmission during their asymptomatic period. Further longitudinal surveillance of these asymptomatic cases via virus nucleic acid testing are warranted.

There is an urgent need for new antifungal agents to treat or combat fungal infection in humans and plants. Antifungal nucleoside antibiotics are an important family of natural products with distinctive structural features. Understanding their biosynthetic machinery is of great importance for the improvement of antibiotics titers. More importantly, it is a requisite for combinatorial biosynthesis to create hybrid nucleoside antibiotics. We herein focus on findings on the natural and designed biosynthesis of this important family of nucleoside antibiotics.

BackgroundRapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Guangzhou and elsewhere in China. Modes of contact and risk of transmission among close contacts have not been well estimated.MethodsWe included 4950 closes contacts from Guangzhou, and extracted data including modes of contact, laboratory testing, clinical characteristics of confirmed cases and source cases. We used logistic regression analysis to explore the risk factors associated with infection of close contacts.ResultsAmong 4950 closes contacts, the median age was 38.0 years, and males accounted for 50.2% (2484). During quarantine period, 129 cases (2.6%) were diagnosed, with 8 asymptomatic (6.2%), 49 mild (38.0%), and 5 (3.9%) severe to critical cases. The sensitivity of throat swab was 71.32% and 92.19% at first to second PCR test. Among different modes of contact, household contacts were the most dangerous in catching with infection of COVID-19, with an incidence of 10.2%. As the increase of age for close contacts and severity of source cases, the incidence of COVID-19 presented an increasing trend from 1.8% (0-17 years) to 4.2% (60 or over years), and from 0.33% for asymptomatic, 3.3% for mild, to 6.2% for severe and critical source cases, respectively. Manifestation of expectoration in source cases was also highly associated with an increased risk of infection in their close contacts (13.6%). Secondary cases were in general clinically milder and were less likely to have common symptoms than those of source cases.ConclusionsIn conclusion, the proportion of asymptomatic and mild infections account for almost half of the confirmed cases among close contacts. The household contacts were the main transmission mode, and clinically more severe cases were more likely to pass the infection to their close contacts. Generally, the secondary cases were clinically milder than those of source cases.

Background: The phenomenon of patients recovering from COVID-19 who tested positive for SARS-CoV-2 after discharge (redetectable as positive, RP) has been repor

Background: Rapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Guangzhou and elsewhere in China Modes of contact and risk of transmission

Staurosporine, belonging to indolocarbazole compounds, is regarded as an excellent lead compound for synthesizing antitumor agents as a potent inhibitor against various protein kinases. In this study, two separate clusters (cluster A and cluster B), corresponding to biosyntheses of K-252c (staurosporine aglycone) and sugar moiety, were identified in Streptomyces fradiae CGMCC 4.576 and heterologously expressed in Streptomyces coelicolor M1146 separately or together. StaR, a cluster-situated LAL family regulator, activates staurosporine biosynthesis by binding to the promoter regions of staO-staC and staG-staN. The conserved sequences GGGGG and GCGCG were found through gradually truncating promoters of staO and staG, and further determined by mutational experiments. Overexpression of staR with the supplementation of 0.01 g L-1 FeSO4 increased staurosporine production to 5.2-fold compared with that of the parental strain Streptomyces fradiae CGMCC 4.576 in GYM medium. Our results provided an approach for improvement of staurosporine production mediated by a positive regulator and established the basis for dissecting the regulatory mechanisms of other indolocarbazole compounds with clinical application value.

Neomycin, an aminoglycoside antibiotic, is widely used in the livestock husbandry due to its higher antimicrobial activity and availability of feed additives in animals. However, its production yield is relatively low and cannot meet the needs of developing market and clinical application. Here, the entire natural neo cluster was cloned from Streptomyces fradiae CGMCC 4.576 by φBT1 integrase-mediated site-specific recombination. Then, the rational reconstruction of the neo cluster was performed by using λ-Red-mediated PCR targeting for improving neomycin production. In order to coordinate with this attempt, the supplementation of suitable precursors was carried out. The constructed recombinant strain Sf/pKCZ03 has multi-copy of the neo cluster modified by disrupting the negative regulatory gene neoI and replacing the native promoter of the neoE-D with PkasO*. Compared to the yield (1282 mg/L) of Streptomyces fradiae CGMCC 4.576, the engineered strain Sf/pKCZ03 had a 36% enhancement of neomycin production. Quantitative real-time PCR analysis revealed the increased transcription of structural genes (neoE, neoB, neoL, aacC8) and regulatory genes (neoR, neoH) in Sf/pKCZ03. Additionally, under the supplementation of 1 g/L N-acetyl-D-glucosamine and 5 g/L L-glutamine, the yield of engineered strain Sf/pKCZ03 showed 62% and 107% improvements compared to that of the wild-type strain in the original medium, respectively. These findings demonstrated that engineering the antibiotic gene cluster in combination with precursors feeding was an effective approach for strain improvement, and would be potentially extended to other Streptomyces for large-scale production of commercialized antibiotics.

The introduction of oxygen in ZnTe provides an isoelectronic radiative defect that can form an intermediate band attractive for optoelectronic applications. ZnTe also exhibits native deep level emission in close spectral proximity to oxygen emission, which can obscure the understanding of these electronic states. The photoluminescence characteristics of ZnTe epitaxial layers on GaAs are studied with the intentional introduction of oxygen and native deep levels. Native deep level emission at 1.8 eV demonstrates a reduced quenching in emission at increasing temperature and dominates at room temperature. However, the overall radiative emission of oxygen states at 1.9 eV in ZnTeO is reduced in samples in which native deep level emission is present. Despite the radiative nature and weak temperature dependence of luminescence efficiency, oxygen incorporation demonstrates significantly higher radiative emission that is maximized with the reduction of the native deep level emission.

Hole diffusion lengths were determined for two epitaxial n-type ZnSe layers by fitting the measured photoluminescence spectra to a theoretical expression which contains the measured absorption constants. The room temperature hole diffusion lengths are found to be 0.1 and 0.06 μm for ZnSe with electron concentrations of 1.6 × 1017 and 9.0 × 1017 cm-13, respectively. These short diffusion lengths are attributed to a strong Hall-Shockley-Read recombination.

Thermal emission from a deep level to the conduction band in zinc selenide gives an apparent activation energy of 0.33 eV. The photoionization spectrum shows two thresholds, attributed to transitions from the level to the Г and L valleys. An intervalley spacing of 1.26 ± 0.06 eV is deduced.

The M-centre produces a deep level in ZnSe which is characterized by a distinctive peak in the photoionization spectrum to the valence band, the peak being at 0.83 eV. The centre occurs in most samples of ZnSe whatever the growth method. It can provide the dominant recombination route and therefore can be the limiting factor in the production of efficient blue luminescence at room temperature. Its identity is unclear. We have made photocapacitance measurements on ZnSe epitaxial layers grown by MOCVD. We find that previously published spectra are a superposition of the M-centre spectrum and the spectrum of another centre. The concentration of the M-centre varies with the growth conditions. In the past the carrier mobility and the ratio of near-band-edge to deep-level radiative emission intensity have been used as figures of merit for ZnSe. Our work indicates that the M-centre concentration could be at least as important in material characterization.

The resistivity of n-type MOCVD ZnSe with as-grown carrier concentration of 1018 cm-3 can be changed by three orders of magnitude by annealing between 300 and 400°C. The process involved has an activation energy of only 0.26 eV and appears to be caused by a lattice defect acting as an acceptor.

It is shown that the blue luminescence band appearing at room temperature in ZnSe is seen in metalorganic chemical vapor deposition (MOCVD) epilayers with carrier concentration 1×1018 cm−3. The photon energy at the emission peak is the same in this material as in material with much lower carrier concentration. Properties of the blue band are surveyed to discriminate between different possible assignments. It is concluded that Shirakawa and Kukimoto [J. Appl. Phys. 51, 2014 (1980)] were correct in assigning it to a transition between a free hole and an electron bound to a donor. However, not all donors contribute. There is a cutoff energy within the spread of donor levels above which there is negligible contribution to the emission. It is suggested that the cutoff corresponds to a localization edge of the same nature as the mobility edge.