A practical preparation of bicyclic boronates via metal-free heteroatom-directed alkenyl sp2-C‒H borylation.

Bicyclic boronates play critical roles in the discovery of functional materials and antibacterial agents, especially against deadly bacterial pathogens. Their practical and convenient preparation is in high demand but with great challenge. Herein, we report an efficient strategy for the preparation of bicyclic boronates through metal-free heteroatom-directed alkenyl sp2-C‒H borylation. This synthetic approach exhibits good functional group compatibility, and the corresponding boronates bearing halides, aryls, acyclic and cyclic frameworks are obtained with high yields (43 examples, up to 95% yield). Furthermore, a gram-scale experiment is conducted, and downstream transformations of the bicyclic boronates are pursued to afford natural products, drug scaffolds, and chiral hemiboronic acid catalysts.

Study on Bayesian Skew-Normal Linear Mixed Model and Its Application in Fire Insurance.

Fire insurance is a crucial component of property insurance, and its rating depends on the forecast of insurance loss claim data. Fire insurance loss claim data have complicated characteristics such as skewness and heavy tail. The traditional linear mixed model is commonly difficult to accurately describe the distribution of loss. Therefore, it is crucial to establish a scientific and reasonable distribution model of fire insurance loss claim data. In this study, the random effects and random errors in the linear mixed model are firstly assumed to obey the skew-normal distribution. Then, a skew-normal linear mixed model is established using the Bayesian MCMC method based on a set of U.S. property insurance loss claims data. Comparative analysis is conducted with the linear mixed model of logarithmic transformation. Afterward, a Bayesian skew-normal linear mixed model for Chinese fire insurance loss claims data is designed. The posterior distribution of claim data parameters and related parameter estimation are employed with the R language JAGS package to obtain the predicted and simulated loss claim values. Finally, the optimization model in this study is used to determine the insurance rate. The results demonstrate that the model established by the Bayesian MCMC method can overcome data skewness, and the fitting and correlation with the sample data are better than the log-normal linear mixed model. Hence, it can be concluded that the distribution model proposed in this paper is reasonable for describing insurance claims. This study innovates a new approach for calculating the insurance premium rate and expands the application of the Bayesian method in the fire insurance field.

Prolonged Intermittent Renal Replacement Therapy Combined with Hemoperfusion Can Improve Early Recovery of Moderate and Severe Acute Pancreatitis, Especially in Patients with Acute Kidney Injury.

INTRODUCTION: The aim of this study was to investigate the efficacy of prolonged intermittent renal replacement therapy (PIRRT) plus hemoperfusion (HP) in treating moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP). METHODS: A total of 105 MSAP and SAP patients were enrolled. Sixty of them received routine internal medical therapy (control group), and 45 received PIRRT and HP in addition to routine internal medical therapy (PIRRT + HP group). The vital signs, laboratory results, and the Acute Physiology and Chronic Health Evaluation II (APACHE II) score were compared between the two groups before treatment and on the 3rd and 7th days of treatment. RESULTS: No deaths or treatment-related serious adverse reactions occurred in both groups. After 3 and 7 days of treatment, the APACHE II score decreased more significantly in the PIRRT + HP group than in the control group (3 days: 5.47 [±3.30] vs. 7.53 [±3.89], p = 0.005. 7 days: 4.82 [±3.49] vs. 6.87 [±3.54], p = 0.004). After 3 days of treatment, the inflammatory combination parameters systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) in the PIRRT + HP group decreased more significantly than those in the control group (SII: 1,239.00 [737.80-1,769.00] vs. 2,013.00 [1,260.00-3,167.00], p = 0.001. NLR: 8.78 [±4.52] vs. 11.88 [±7.30], p = 0.009). After 7 days of treatment, SII, NLR, and hypersensitive C-reactive protein decreased significantly compared with baseline, but no statistical differences between the two groups were observed. AST in both groups remained stable with treatment. There was no significant difference in baseline creatinine between the two groups of AKI patients, but after 3 and 7 days of treatment, the proportion of acute kidney injury (AKI) patients in the PIRRT + HP group whose creatinine decreased by 50% from baseline or fell to the normal range was significantly higher than that in the control group (p < 0.05). CONCLUSION: PIRRT + HP therapy could not only improve the general conditions, as measured by APACHE II score, but also reduce the inflammatory cascade of patients with acute pancreatitis. For MSAP and SAP patients complicated with AKI, this therapy may accelerate the recovery of renal function.

Telocytes and their structural relationships with surrounding cell types in the skin of silky fowl by immunohistochemistrical, transmission electron microscopical and morphometric analysis.

Telocytes (TCs), a novel type of interstitial cells, were identified in various animals. Since TCs have not observed in avian skin, hence, we carried out immunohistochemistrical and transmission electron microscopical studies in the skin of the silky fowl to investigate the TCs. TCs appear as CD34, c-Kit, and PDGFRα immunopositive. The elongated TCs with 2 long and thin telopodes (Tps) are located in the dermis. Generally, a TC possesses a fusiform, ovoid and polygonal cell body with 2 Tps (lengths = 5.27-21.85 µm), which are uneven in thickness including thick sections - podoms (diameters = 0.40-0.47 µm) and thin sections - podomers (diameters = 0.03-0.04 µm). TCs/Tps are observed frequently in close proximity to neighboring cell types/structures, such as adipocytes, collagen fibers, and capillaries. Under a magnified field, homocellular TCs/Tps contacts are observed through gap junctions (distances = 0.01-0.05 µm), whereas some of TCs/Tps have heterocellular close contacts by point contacts with surrounding cells, including stem cells and melanocytes. The multivisicular bodies, especially exosomes (diameters = 0.09-0.23 µm) releasing from TCs/Tps are observed in close proximity to TCs/Tps. Our results illustrated that the novel type of interstitial cells - TCs are present in the dermis of the silky fowl, and they have special structural relationships with surrounding cell types. The study provides histological evidence for TCs involvement in intercellular communication, skin regeneration, and pigmentogenesis in avian skin.

Ternary catalyst Mn-Fe-Ce/Al2O3 for the ozonation of phenol pollutant: performance and mechanism.

In this study, a novel ternary catalyst Mn-Fe-Ce/Al2O3 was synthesized by co-impregnation method, and was characterized by XRD, SEM, XPS, and FTIR. The catalytic performance of this ternary catalyst was evaluated in the heterogeneous catalytic ozonation of phenol pollutants and it improved the removal rate and mineralization degree of phenol pollutants. The changes of dissolved ozone in water and the TBA experiment proved that the ternary catalyst could accelerate the decomposition of ozone into hydroxyl radicals, thus accelerating the oxidation of phenol. Phosphate experiments and surface hydroxyl density measurements proved that surface hydroxyl was the active site of the catalyst. XPS analysis showed that the ternary catalysts accelerated electron transfer through the redox cycles of Mn2+-Mn3+-Mn4+, Fe2+-Fe3+, and Ce3+-Ce4+, which also contributed to the high catalytic activity. Moreover, the catalyst maintained high catalytic activity after five cycles of use. Therefore, the ternary catalyst was considered an efficient and promising catalyst for catalytic ozonation system.

Aggressive Quarantine Measures Reduce the High Morbidity of COVID-19 in Patients on Maintenance Hemodialysis and Medical Staff of Hemodialysis Facilities in Wuhan, China.

INTRODUCTION: Maintenance hemodialysis (MHD) patients are highly vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Medical staff of dialysis facilities without sufficient biosecurity protection are susceptible once exposed to asymptomatic coronavirus disease 2019 (COVID-19) patients. This study evaluated the epidemiological characteristics of COVID-19 in all MHD patients and medical staff of dialysis facilities in Wuhan, China. METHODS: We collected COVID-19 morbidity and mortality data from MHD patients and medical staff from 52 hemodialysis centers in Wuhan. Then, we analyzed the symptoms and signs of patients and staff in our hospital (Tongji Hospital in Wuhan), and chest CT, SARS-CoV-2 nucleic acid detection and laboratory tests were performed. After aggressive quarantine of the COVID-19 patients, we followed up on the prognosis of them. RESULTS: We analyzed the hemodialysis data from Wuhan and found that 10% of MHD patients and 6.0% of medical staff were suspected of COVID-19. Further detection of SARS-CoV-2 nucleic acid showed that 1.7% of MHD patients and 2.9% of medical staff were confirmed as having COVID-19. In our facility, 18.9% (46/244) of patients and 9.5% (6/63) of medical staff were suspected of COVID-19. Among them, 2.9% (7/244) of MHD patients and 4.8% (3/63) of medical staff tested positive for SARS-CoV-2 were confirmed as having COVID-19. Interestingly, 87.0% of MHD patients suspected of COVID-19 did not have obvious symptoms, but the CT screening showed features of viral pneumonia. There were no significant differences in symptoms, CT findings, comorbidity and laboratory findings of SARS-CoV-2 nucleic-acid-positive and -negative patients. We followed up these patients and found that 57 patients with COVID-19 died (COVID-19 mortality 8.9%). Two patients from our dialysis center with COVID-19 (mortality 4.3%) died. No new infections occurred in our dialysis center after aggressive quarantine was initiated. CONCLUSIONS: The SARS-CoV-2 infection rates in MHD patients and medical staff in dialysis facilities were both high in Wuhan. Frequent chest CT and SARS-CoV-2 nucleic acid detection were needed to screen COVID-19 patients in dialysis facilities. Through the lessons of this experience on the aggressive diagnosis and quarantine measures of COVID-19 patients, we hope medical staff avoid more infections in serious epidemic areas.

Loss-of-function mutations in KEAP1 drive lung cancer progression via KEAP1/NRF2 pathway activation.

BACKGROUND AND PURPOSE: Targeted therapy and immunotherapy have led to dramatic change in the treatment of lung cancer, however, the overall 5-year survival rate of lung cancer patients is still suboptimal. It is important to exploit new potential of molecularly targeted therapies. High-frequency somatic mutations in KEAP1/NRF2 (27.9%) have been identified in lung squamous cell carcinoma. In this research, we explored the role of KEAP1 somatic mutations in the development of LSCC and whether a nuclear factor erythroid 2-related factor 2(NRF2) inhibitor be potential to target lung cancer carrying KEAP1/NRF2 mutations. METHODS: Lung cancer cell lines A549 and H460 with loss-of-function mutations in KEAP1 stably transfected with wild-type (WT) KEAP1 or somatic mutations in KEAP1 were used to investigate the functions of somatic mutations in KEAP1. Flow cytometry, plate clone formation experiments, and scratch tests were used to examine reactive oxygen species, proliferation, and migration of these cell lines. RESULTS: The expression of NRF2 and its target genes increased, and tumor cell proliferation, migration, and tumor growth were accelerated in A549 and H460 cells stably transfected with KEAP1 mutants compared to control cells with a loss-of-function KEAP1 mutation and stably transfected with WT KEAP1 in both in vitro and in vivo studies. The proliferation of A549 cell line trasfected with the R320Q KEAP1 mutant was inhibited more apparent than that of the A549 cell line trasfected with WT KEAP1 after treatment with NRF2 inhibitor ML385. CONCLUSION: Somatic mutations of KEAP1 identified from patients with LSCC likely promote tumorigenesis mediated by activation of the KEAP1/NRF2 antioxidant stress response pathway. NRF2 inhibition with ML385 could inhibit the proliferation of tumor cells with KEAP1 mutation. Video abstract.