Three new LmbU targets outside lmb cluster inhibit lincomycin biosynthesis in Streptomyces lincolnensis.

BACKGROUND: Antibiotics biosynthesis is usually regulated by the cluster-situated regulatory gene(s) (CSRG(s)), which directly regulate the genes within the corresponding biosynthetic gene cluster (BGC). Previously, we have demonstrated that LmbU functions as a cluster-situated regulator (CSR) of lincomycin. And it has been found that LmbU regulates twenty non-lmb genes through comparative transcriptomic analysis. However, the regulatory mode of CSRs' targets outside the BGC remains unknown. RESULTS: We screened the targets of LmbU in the whole genome of Streptomyces lincolnensis and found fourteen candidate targets, among which, eight targets can bind to LmbU by electrophoretic mobility shift assays (EMSA). Reporter assays in vivo revealed that LmbU repressed the transcription of SLINC_0469 and SLINC_1037 while activating the transcription of SLINC_8097. In addition, disruptions of SLINC_0469, SLINC_1037, and SLINC_8097 promoted the production of lincomycin, and qRT-PCR showed that SLINC_0469, SLINC_1037, and SLINC_8097 inhibited transcription of the lmb genes, indicating that all the three regulators can negatively regulate lincomycin biosynthesis. CONCLUSIONS: LmbU can directly regulate genes outside the lmb cluster, and these genes can affect both lincomycin biosynthesis and the transcription of lmb genes. Our results first erected the cascade regulatory circuit of LmbU and regulators outside lmb cluster, which provides the theoretical basis for the functional research of LmbU family proteins.

More than sleep problems? Testing five key health behaviors as reasons for quality of life issues among shift workers.

BACKGROUND: The shift work schedule is a common work arrangement that can disrupt typical sleep-wake rhythms and lead to negative health consequences. The present study aims to examine the effect of shift work on health-related quality of life (QoL) and explore potential behaviorial mediators (i.e., sleep, eating, exercise, smoking, drinking). METHODS: A cross-sectional survey was conducted among 4,449 petroleum workers in southwest China. Data on shift work status, health behaviors, and physical and mental health QoL were collected. We tested our model using path analysis and the Monte Carlo approach among 2,129 included participants. RESULTS: After adjusting for covariates, shift work did not exhibit a significant direct association with QoL. However, shift work indirectly related to poorer physical health quality of life via less frequent healthy food consumption; shift work also indirectly related to poorer mental health QoL via both less frequent healthy food consumption and physical exercise. No significant indirect effects were found via sleeping, smoking, or drinking. CONCLUSIONS: Results suggest that shift work presents a challenge for QoL among Chinese petroleum workers due to their lesser engagement in two specific health behaviors: healthy eating and physical exercise. Healthy eating and exercise may present an even more prominent threat to shift workers' QoL than sleep and substance use. Strategies targeting shift work schedule as well as eating and exercise behaviors may help protect against poor QoL and adverse physical and mental health outcomes in this vulnerable group.

Identification of and solution for false D-dimer results.

BACKGROUND: Clinically, D-dimer (DD) levels are mainly used to exclude diseases such as deep venous thrombosis (DVT). In clinical testing, DD assays can be subjected to interference that may cause false results, which directly affect the clinical diagnosis. Our hypothesis was that the 95% confidence intervals (CIs) of the fibrin degradation product (FDP)/DD and fibrinogen (Fib)/DD ratios were used to identify these false results and corrected via multiple dilutions. METHODS: In total, 16 776 samples were divided into three groups according to the DD levels detected by Sysmex CS5100 and CA7000: Group A, DD ≥ 2.0 µg/mL fibrinogen equivalent unit (FEU); group B, 0.5 < DD < 2.0 µg/mL FEU; and group C, DD ≤ 0.5 µg/mL FEU. The 95% CIs of the FDP/DD and Fib/DD ratios were calculated. Six abnormal DD results were found according to the 95% CIs. For verification, we performed multiple dilutions, compared the results with those of other instruments, and tested the addition of heterophilic blocking reagent (HBR). RESULTS: The median and 95% CI of the FDP/DD ratio were 3.76 and 2.25-8.15 in group A, 5.63 and 2.86-10.58 in group B, 10.23 and 0.91-47.71 in groups C, respectively. For the Fib/DD ratio, the 95% CIs was 0.02-2.21 in group A, 0.68-8.15 in group B, and 3.82-55.27 in groups C. Six abnormal results were identified after multiple dilutions, by comparison with other detection systems, and after HBR addition. CONCLUSIONS: The FDP/DD ratio is more reliable for identifying false results. If the FDP/DD ratio falls outside the 95% CI, it should be verified by different methods.

What makes D-dimer assays suspicious-heterophilic antibodies?

BACKGROUND: Heterophilic antibodies are still an important source of interference in immunoassays, but reports of interference with D-dimers are rare. Are D-dimer level abnormalities, found in the clinic, caused by heterophilic antibodies as well, or are other mechanisms involved? We will elaborate on this issue through two different examples in this article. METHODS: Serum from two patients with significantly elevated levels of D-dimers were measured and compared by different methods, diluted, and dealt with heterophilic antibody blockers. At the same time, to retrieve the interference, we focused on the cause of D-dimer false positives and made a systematic review of the literature. RESULTS: The D-dimer values were normal (0.49 and 0.15 µg/mL) detected with different testing method and decreased after addition of heterophilic antibody blocking reagent. According to literature data, there were 66.7% (4/6) references showed the interference were heterophilic antibody. CONCLUSIONS: The influence of heterophilic antibodies on the measurement of D-dimers remains a big challenge. Different measuring instruments and methods may have significant differences in the measurement of D-dimers. By using a combination of instrumental methods for measuring, incorporating heterophilic antibody blockers, and combining with clinical performance and imaging data, most of the interference can be eliminated.

Discovery of Two New Sorbicillinoids by Overexpression of the Global Regulator LaeA in a Marine-Derived Fungus Penicillium dipodomyis YJ-11.

Overexpression of the global regulator LaeA in a marine-derived fungal strain of Penicillium dipodomyis YJ-11 induced obvious morphological changes and metabolic variations. Further chemical investigation of the mutant strain afforded a series of sorbicillinoids including two new ones named 10,11-dihydrobislongiquinolide (1) and 10,11,16,17-tetrahydrobislongiquinolide (2), as well as four known analogues, bislongiquinolide (3), 16,17-dihydrobislongiquinolide (4), sohirnone A (5), and 2',3'-dihydrosorbicillin (6). The results support that the global regulator LaeA is a useful tool in activating silent gene clusters in Penicillium strains to obtain previously undiscovered compounds.

[Quantitative Analysis of Mn in Soil Samples Using LIBS].

The trace element of Manganese element in the agricultural farm (Anhui Huaiyuan Nongkang) soil was quantitatively analyzed by Laser-induced breakdown spectroscopy. The line of 403.1 nm was selected as the analysis line of Mn. The matrix element of Fe in soil was chosen as the internal calibration element and the analysis line was 407.2 nm. Ten soil samples were used to construct calibration curves with traditional method and internal standard method, and four soil samples were selected as test samples. The experimental results showed that the fitting correlation coefficient (r) is 0.954 when using the traditional method, the maximum relative error of the measurement samples is 5.72%, and the detection limit of Mn in soil is 93 mg x kg(-1). While using the internal standard method to construct the calibration curve, the fitting correlation coefficient (r) is 0.983, the relative error of measurement samples is reduced to 4.1%, and the detection limit of Mn in soil is 71 mg x kg(-1). The result indicates that LIBS technique can be used to detect trace element Mn in soil. In a certain extent, the internal standard method can improve the accuracy of measurement.

Association of Apolipoprotein E Gene Polymorphism with Type 2 Diabetic Nephropathy in the Southern Chinese Population.

Background: Common polymorphisms within the apolipoprotein E (APOE) gene are rs429358 and rs7412, which result in three major alleles (ɛ2, ɛ3, and ɛ4) and six genotypes (E2/E2, E2/E3, E3/E3, E3/E4, E4/E4, and E2/E4). Although APOE gene polymorphisms have been suggested to be associated with the development of diabetic nephropathy (DN), their potential association remains unclear in different regions. This study aims to unveil the genetic effects of APOE gene polymorphisms on DN susceptibility and serum lipid profiles in southern Chinese population. Methods: A total of 306 DN patients and 483 type 2 diabetic patients as controls were included in the study. The APOE gene polymorphisms were analyzed by polymerase chain reaction (PCR) microarray gene chip. Relevant medical records and information of these participants were collected. Results: There were statistically significant differences (p < 0.05) in gender, SBP, hypertension, hyperuricemia, UTP, TG and HDL-C between DN patients and controls. DN patients exhibited a higher frequency of the ε2 allele and E2/E3 genotype than controls (p < 0.001). Logistic regression analysis indicated that the ε2 allele and E2/E3 genotype were independent risk factors (adjusted OR: 3.237, 95% CI: 1.789-5.854, p < 0.001; adjusted OR: 3.453, 95% CI: 1.873-6.368, p < 0.001), while the ε3 allele or E3/E3 genotype might serve as protective role (adjusted OR: 0.395, 95% CI: 0.255-0.612, p < 0.001) for development of DN. Conclusion: Our study indicates a correlation between APOE polymorphisms and DN in the southern Chinese Hakka population. Specifically, individuals carrying the APOE ε2 allele and E2/E3 genotype are at a higher risk of developing DN. Conversely, those with the APOE ε3 allele and E3/E3 genotype have a lower risk of DN in southern Chinese population.

Spatial Pattern Characteristics and Factors for the Present Status of Rural Settlements in the Lijiang River Basin Based on ArcGIS.

In China, rural settlements have undergone significant changes in response to dramatic socioeconomic shifts. However, there has not been any report on rural settlements in the Lijiang River Basin. In this study, ArcGIS 10.2 (including hot spot analysis and kernel density estimation) and Fragstats 4.2 (such as the landscape pattern index) software were used to analyze the spatial pattern and causes of rural settlements in the Lijiang River Basin. The Lijiang River Basin is mainly dominated by micro- and small-sized rural settlements with small areas. Moreover, the results of a hot spot analysis showed that micro- and small-sized rural settlements were mainly located in the upper reaches, and medium- and large-sized rural settlements were mainly located in the middle and lower reaches. The kernel density estimation results showed that the distribution characteristics of the rural settlements in the upper, middle, and lower reaches were significantly different. The spatial forms of rural settlements were affected by physiographic factors such as elevation and slope, karst landforms, and river trunk channels as well as the national policy system, tourism economic development, town distribution, historical heritage, and minority culture. This study is the first to systematically elaborate on the rural settlement pattern and its internal logic from the perspective of the Lijiang River Basin, providing a basis for the optimization and construction of the rural settlement pattern.

Clinical, epidemiological, and drug resistance insights into HIV-positive patients in Meizhou, China.

The acquired immunodeficiency syndrome (AIDS) epidemic, resulting from human immunodeficiency virus (HIV) infection, exhibits distinct regional characteristics. This study undertakes a retrospective analysis of the epidemiological and clinical features of 195 HIV-positive cases in Meizhou, China, from May 1, 2018 to December 31, 2019. Western blotting (WB) confirmed and assessed these cases. Notably, the majority of cases emanated from socio-economic groups with comparatively lower levels of education, with 80% being male. Strikingly, 90% of the cases were found to be in the middle to late stages of infection based on CD4+ T cell counts. Among the 30 different serum antibody profiles examined, reactivity with seven bands (p24, p31, gp41, p51, p66, gp120, and gp160) emerged as the most commonly observed WB pattern. The absence of specific bands, specifically p55 (17.44%), p39 (32.31%), and p17 (25.64%) were most frequent, with the detection frequency of p17 bands significantly reduced among cases in the AIDS and middle stages. An analysis of drug resistance genotypes indicated that, despite viral mutations conferring resistance to certain reverse transcriptase inhibitors, the first-line treatment regimen remained effective for patients in Meizhou. Notably, mutations resistant to protease inhibitors were infrequent (2.7%), suggesting that incorporating protease inhibitors into the treatment regimen may enhance therapeutic outcomes for local patients. These findings provide essential insights into the specific epidemiological patterns, serum antibody profiles, and drug resistance genotypes of HIV-infected patients in Meizhou. Significantly, this research contributes to the formulation of future treatment strategies tailored to the local context.

Exploring the effect of use contexts on user engagement toward tourism short video platforms.

With tourism short video platforms' increasingly fierce competition, retaining existing users and improving engagement has taken on greater theoretical and practical significance. Based on the self-system model of motivational development, this study, involving an empirical analysis of 252 user data samples, establishes a research model to determine how the use contexts affect users' psychological process and finally lead to behavioral engagement. In particular, four use contexts of tourism short video platforms are proposed-namely, information acquisition, leisure and entertainment, attention obtainment, and social interaction. Different use contexts differ in the degree to which they satisfy users' three psychological needs, thus influence their attitudinal engagement and behavioral engagement. The research results can provide theoretical and practical references on how to improve user engagement toward tourism short video platforms.

Trends in Incidence and Mortality of Stroke in China From 1990 to 2019.

Objective: Stroke is a leading cause of mortality and morbidity globally. This study aimed to analyze the burden and 30-year trends of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) in China. Methods: Data that include incidence and mortality of stroke in China from January 1, 1990 to December 31, 2019 were derived from the Global Burden of Disease (GBD) study 2019. The absolute numbers of incident cases and deaths over the time, and age-standardized rates per 100,000, such as age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR), were analyzed. Results: In 2019, there were 3.9 (95% uncertainty intervals (UI) 3.4-4.5) million incident cases and 2.1 (3.4-4.5) million deaths related to stroke in China. The ASIR and ASMR of stroke in China was 200 (176-230) and 127 (110-144). From 1990 to 2019, the ASIR of ischemic stroke had increased by 35.0% (29.0-40.0) while the ASIR of ICH and SAH had decreased by -53.0% (-56.0 to -50.0) and by -39.0% (-44.0 to -35.0), respectively. The ASMR of ischemic stroke had increased by 3.0% (-26.0 to 16.0) while the ASMR of ICH and SAH had decreased by -48.0% (-59.0 to -38.0) and by -84.0% (-89.0 to -69.0), respectively. Conclusion: Although the incidence and mortality rates of stroke in China were decreased from 1990 to 2019, the number of incident cases and deaths nearly doubled. A sharp increase in the incidence rate of ischemic stroke was observed. A higher incidence rate of ischemic stroke in the women was also observed.

Heterologous expression and metabolic engineering tools for improving terpenoids production.

Terpenoids, also referred to as isoprenoids, are the largest group of natural compounds which have contributed significantly to the pharmaceutical industry. The challenges in producing bioactive terpenoids from their original host or by organic synthesis methods spurred the endeavors of producing terpenoids in heterologous host. Modern advances utilizing synthetic biology and biological engineering tools have provided a variety of pharmaceutical terpenoids in large-scale and with diversified structures. In this review, we will summarize the progress in production of typical terpenoids skeletons using heterologous expression method assisted by metabolic engineering techniques, with the purpose of enlightening further efforts in developing advanced cell factories for producing terpenoid based pharmaceuticals.

Overexpression of Global Regulator PbrlaeA Leads to the Discovery of New Polyketide in Fungus Penicillium Brocae HDN-12-143.

Overexpression of the PbrlaeA gene of the fungus Penicillium brocae HDN-12-143 resulted in the isolation of four compounds including fumigatin chlorohydrin (1), whose configuration has not been reported before, and one new compound iso-fumigatin chlorohydrin (2). All structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data, 13C NMR calculations, and ECD calculations. Compounds 1 and 2 exhibited cytotoxic activity against HL-60 with IC50 of 18.63 and 24.83 µM.