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Protein kinases C (PKCs) are a family of serine/threonine kinases involved in various cellular processes, including proliferation, differentiation, cell survival, and apoptosis. Here, we report the identification, structure-activity relationship (SAR), and 3D-QSAR studies of 69 natural indolocarbazoles, including 15 new compounds, from marine streptomyces strains. Interestingly, we found that the chair conformational isomer of 7-oxo-staurosporine (compound 15) inhibited PKCθ more potently than the corresponding boat isomer. An evaluation of kinase selectivity and antitumor efficacy revealed that 15 was a potent dual PKCθ/δ inhibitor and that it could efficiently inhibit tumor growth in pancreatic cancer (PC) by inducing cellular apoptosis and suppressing the NF-κB/p-P65 pathway. In addition, we demonstrated that overexpression of p-PKCδ and p-P65 was associated with poor survival rates in patients with PC, and p-PKCθ expression also showed significant positive correlations with p-PKCδ and p-P65 levels. Finally, the PC patient-derived xenograft model further confirmed the potential anti-PC efficacy of 15.

This study aimed to determine the spatiotemporal distribution and epidemiological characteristics of hospital admissions for carbon monoxide poisoning (COP) in Guangdong, China, from 2013 to 2020.Data on age- and sex- specific numbers of hospital admissions due to COP in Guangdong (2013-2020) were collected. Daily temperatures were downloaded through the China Meteorological Data Sharing Service System. We analyzed temporal trends through time series decomposition and used spatial autocorrelation analysis to detect spatial clustering. The distributed lag nonlinear model was used to quantify the effects of temperature.There were 48,854 COP admissions over the study period. The sex ratio (male to female) was 1:1.74. The concentration ratios (M) ranged from 0.73-0.82. The highest risk occurred in January (season index = 3.59). Most cases were concentrated in the northern mountainous areas of Guangdong with high-high clustering. COP in the study region showed significant spatial autocorrelation, and the global Moran'sCOP in Guangdong province showed significant temporal and spatial heterogeneity. Low temperature was associated with a high risk of COP, and the influence had a lag lasting 7 days.

We aimed to investigate and interpret the associations between socioeconomic factors and the prevalence, awareness, treatment, and control of hypertension at the provincial level in China.A nationally and provincially representative sample of 179,059 adults from the China Chronic Disease and Nutrition Surveillance study in 2015-2016 was used to estimate hypertension burden. The spatial Durbin error model was fitted to investigate socioeconomic factors associated with hypertension indicators.Overall, it was estimated that 29.20% of the participants were hypertensive nationwide, among whom, 34.32% were aware of their condition, 27.69% had received antihypertensive treatment, and 7.81% had controlled their condition. Per capita gross domestic product (GDP) was associated with hypertension prevalence (coefficient: -2.95, 95%Hypertension indicators were not only directly influenced by socioeconomic factors of local area but also indirectly affected by characteristics of geographical neighbors. Population-level strategies should involve optimizing supportive socioeconomic environment by integrating clinical care and public health services to decrease hypertension burden.

Eleven new pyrimidine nucleosides (1-11) and 12 known analogues (12-23) were isolated from the marine-derived Streptomyces sp. SSA28. All of the new structures were elucidated by extensive NMR spectroscopic analysis and HRESIMS data. The absolute configurations of compound 1 were determined by X-ray diffraction. The configurations of 2-16 were investigated by ECD calculations. Compounds 11-16 showed cytotoxicity against HCT-116 human colon cancer cell lines with IC50 values from 0.39 ± 0.03 to 6.63 ± 0.47 μM.

To explore the association between soil selenium levels and the risk of diabetes in Chinese adults aged 35-74 years.Data for this study were derived from the China Chronic Diseases and Behavioral Risk Factors Surveillance 2010 survey. Selenium concentrations in soil were obtained from the Atlas of Soil Environmental Background Values in China. A two-level binary logistic regression model was used to determine the association between soil selenium concentrations and the risk of diabetes, with participants nested within districts/counties.A total of 69,332 participants aged 35-74 years, from 158 districts/counties were included in the analysis. Concentrations of selenium in soil varied greatly across the 158 districts/counties, with a median concentration of 0.219 mg/kg (Excessive selenium concentrations in soil could increase the risk of diabetes among Chinese adults aged 35-74 years.

Eleven new pyrimidine nucleosides (

Four new medermycin-type naphthoquinones, strepoxepinmycins A-D (1-4), and one known compound, medermycin (5), were identified from Streptomyces sp. XMA39. Their structures were elucidated by analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and ECD calculations. Among these compounds, strepoxepinmycin A (1) represents a rare 5,10-oxepindione ring system typically formed by a Baeyer-Villiger oxidation, and strepoxepinmycin B (2) is an isolation artifact derived from 1. Bioactivity evaluations of these compounds showed that compounds 3 and 4 exhibited cytotoxicity against HCT-116 and PC-3 cancer cell lines and 4 exhibited moderate inhibition of ROCK 2 protein kinase. In addition, all of the new compounds showed antibacterial activity against Escherichia coli and methicillin-resistant Staphylococcus aureus and antifungal activity against Candida albicans.

Aiming to improve positioning precision of the GPS/INS integrated navigation system during GPS outages, a novel model combined with strong tracking Kalman filter (STKF) and improved Radial Basis Function Neural Network(IRBFNN) algorithms is proposed and tested. STKF is used to estimate INS errors as a replacement of Kalman filter (KF), and IRBFNN is trained based on STKF when GPS works well and applied to predict INS errors during GPS outages. In the IRBF neural network, the width of the hidden layer and kernel function are optimized by using genetic algorithm to obtain a high precision generalization ability of RBF network structure. The simulation indicate that the proposed model can effectively provide high accurate corrections to the standalone INS during GPS outages.

By analyzing the relationship between the GDOP value and the area of the polygon formed with the endpoints of the satellite-receiver unit vectors in 2-D, the optimal satellite-receiver geometry (SRG) and the minimum GDOP value of n satellites( 4 n  ) in 3-D were deduced in this paper. Based on the minimum GDOP value and the optimal SRG in 3-D, a satellite selection algorithm is proposed to solve the problem of selecting more than 4 satellites from GNSS (Global Navigation Satellite Systems). The good performance of this algorithm on improving satellite selection efficiency with less sacrifice of the GDOP value is illustrated by simulation.

To analyze the stress distribution induced by simulated intra-oral loads on ceramometal crowns with different length of shoulder porcelain in labial margins.Eighteen two-dimensional finite element models of the maxillary central incisor restored with ceramometal crowns were constructed which were designed with different labial terminal locations of metal coping. Different coping alloys and marginal designs were employed in the crown models. The stresses of porcelain veneers and adhesive layers in all models were estimated with different loading locations and angles.Although coping alloys and marginal designs were different, the labial terminal locations of metal coping had no influence on the stress distribution of porcelain veneers and adhesive layers.The coping design of short labial margin to add the length of shoulder porcelain of ceramometal restorations can be used clinically.