Hepatic Sinusoid Capillarizate via IGTAV/FAK Pathway Under High Glucose.

The incidence of diabetic patients with non-alcoholic fatty liver disease (NAFLD) is continuously increasing worldwide. However, the specific mechanisms of NAFLD patients with diabetes are still not clear. Recent studies have indicated that integrins play an important role in NAFLD. In this study, we considered the relationship between integrin αv (IGTAV)/FAK pathway and sinusoidal capillarization. We investigated the difference between the expression of IGTAV, laminin (LN), focal adhesion kinase (FAK), and phosphor-FAK protein in human liver sinusoidal endothelial cells (HLSECs) to explore the specific mechanisms of the diseases of NAFLD with diabetes under high glucose. We cultured and identified the HLSECs and constructed the recombinant lentivirus vector with IGTAV shRNA by quantitative real-time PCR (qRT-PCR) to silence the IGTAV gene. Cells were divided into groups of 25 mmol/L glucose and 25 mmol/L mannitol. We measured the protein levels of IGTAV, LN, FAK, and phosphor-FAK by western blot at 2 h, 6 h, and 12 h before and after IGTAV gene silencing. The lentivirus vector was successfully constructed with IGTAV shRNA. The HLSECs under high glucose were observed by scanning electron microscope. SPSS19.0 was used for statistical analysis. High glucose significantly increased the expression of IGTAV, LN, and phosphor-FAK protein in HLSECs; the shRNA IGTAV could effectively inhibit the expression of phosphor-FAK and LN at 2 h and 6 h. Inhibition of the phosphor-FAK could effectively decrease the expression of LN in HLSECs at 2 h and 6 h under high glucose. Inhibition of IGTAV gene of HLSECs under high glucose could improve hepatic sinus capillarization. Inhibition of IGTAV and phosphor-FAK decreased the expression of LN. High glucose led to hepatic sinus capillarization via IGTAV/ FAK pathway.

Corrigendum: Molecular epidemiology and mechanism of Klebsiella pneumoniae resistance to ertapenem but not to other carbapenems in China.

[This corrects the article DOI: 10.3389/fmicb.2022.974990.].

Molecular epidemiology and mechanism of Klebsiella pneumoniae resistance to ertapenem but not to other carbapenems in China.

Resistance to only ertapenem is an unusual phenotype of carbapenem-resistant Klebsiella pneumoniae (CRKP). This study aimed to investigate the molecular epidemiology and underlying mechanism involved in ertapenem resistance of K. pneumoniae strains that are susceptible to meropenem and imipenem. Among the 697 K. pneumoniae strains isolated from 11 grade A hospitals in China, 245 were CRKP strains, of which 18 strains resistant only to ertapenem were isolated. The genotypes, phenotypes, drug resistance homology, and drug sensitivity were analyzed; moreover, the expressions of efflux pump components and outer membrane proteins were assessed. The whole genomes of these 18 strains were sequenced and analyzed for mutations leading to drug resistance. The results revealed that ertapenem resistance may be related to ramR mutation. The function of ramR was confirmed using gene complementation to the original strain to determine the mechanism underlying ertapenem resistance of K. pneumoniae strains. In total, 7.4% of the tested CRKP strains were resistant only to ertapenem. None of these strains contained carbapenemase genes. Of the 18 ertapenem-resistant strains, 17 expressed the efflux pump, and outer membrane protein expression was reduced or absent in 4 strains. Whole-genome sequencing revealed the presence of mutations that introduced premature ramR codons stop in 14 strains (77.78%). When a functional copy of ramR was restored in the 14 strains, the minimum inhibitory concentration of ertapenem decreased, inhibition of efflux pumps was not detected, and the expression of outer membrane protein OmpK35 was either increased or was restored. These findings reveal the existence of ertapenem-resistant K. pneumoniae exhibiting no clonal transmission between strains. Mutations in ramR were demonstrated to cause efflux pump inhibition and over-expression of outer membrane protein OmpK35 in some strains, which is implicated in ertapenem resistance only in K. pneumoniae.

150 Gbit/s 1 km high-sensitivity FSO communication outfield demonstration based on a soliton microcomb.

A high-sensitivity and large-capacity free space optical (FSO) communication scheme based on the soliton microcomb (SMC) is proposed. Using ultra-large bandwidth stabilized SMC with a frequency interval of 48.97 GHz as the laser source, 60 optical wavelengths modulated by 2.5 Gbit/s 16-Pulse position modulation (PPM) are transmitted in parallel. A corresponding outfield high-sensitivity 150 Gbit/s FSO communication experiment based on the SMC was carried out with 1 km space distance. Our experimental results show that the best sensitivity of the single comb wavelength which has higher OSNR can reach -52.62 dBm, and the difference is only 1.38 dB from the theoretical limit under the BER of 1 × 10-3 without forward error correction (FEC). In addition, at BER of 1 × 10-3, 16-PPM has a higher received sensitivity of 6.73dB and 3.72dB compared to on-off keying (OOK) and differential phase shift keying (DPSK) respectively. Meanwhile, taking the advantage of multi-channel SMC, 60 × 2.5 Gbit/s can achieve 150 Gbit/s large-capacity free-space transmission. For comparison, commercially available single-wavelength laser based FSO communication system have also been performed in the outfield. The outfield experimental results demonstrated the feasibility of high-sensitivity, large-capacity PPM FSO communication based on SMCs and provided a new perspective for the future development of large-capacity, long-haul FSO communication.

Rhodium-catalyzed intermolecular enantioselective Alder-ene type reaction of cyclopentenes with silylacetylenes.

The Alder-ene type reaction between alkenes and alkynes provides an efficient and atom-economic method for the construction of C-C bond, which has been widely employed in the synthesis of natural products and other functional molecules. The intramolecular enantioselective Alder-ene cycloisomerization reactions of 1,n-enynes have been extensively investigated. However, the intermolecular asymmetric version has not been reported, and remains a challenging task. Herein, we describe a rhodium-catalyzed intermolecular enantioselective Alder-ene type reaction of cyclopentenes with silylacetylenes. A variety of chiral (E)-vinylsilane tethered cyclopentenes bearing one quaternary carbon and one tertiary carbon stereocenters are achieved in high yields and enantioselectivities. The reaction undergoes carbonyl-directed migratory insertion, ß-H elimination and desymmetrization of prochiral cyclopentenes processes.

Impact on physical and mental health among medical personnel in Wuhan during COVID-19 outbreak: a cluster analysis.

Background: Increased stress among medical personnel had been reported in previous virus outbreaks. The novel coronavirus disease (COVID-19) emerged in December 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). No qualitative assessment has yet described the physical and mental health conditions of frontline medical personnel in the COVID-19 outbreaks. Methods: Here, 251 frontline medical personnel involved in COVID-19 missions completed electronic questionnaires, consisting of 31 categorical variables related to their physical and mental health status, medical history and environmental conditions. We constructed a correlation amongst these variables through pairwise Kendall rank correlation coefficient test. Then, clusters of highly correlated variables were identified using the leading eigenvector. Finally, we used the network and clusters to clarify the correlations amongst variables. Results: This qualitative study identified the six clusters. Cluster 1 was characterized by skin allergy. Cluster 2 was predominantly associated with anxiety. Cluster 3 consisted mostly of respiratory symptoms. The participants in cluster 4 had medical history. Cluster 5 and cluster 6 were characterized by disinfection and demography, respectively. Finally, we revealed three major findings. First, more than 80% of medical personnel worry about COVID-19-related infection and experience newly appearing anxiety (56.2%), airway or heart symptoms (34.3%) and skin allergies (20.3%). Second, COVID-19-related worry significantly associates with all variables in the anxiety and respiratory symptom clusters. Third, new-onset skin allergies did not associate with either disinfection or anxiety, but did associate with a previous history of allergies. Conclusions: COVID-19-related worry leads to physical and mental health problems amongst medical personnel. Effective responses and interventions could relieve a series of new-onset physical and mental health problems.

MicroRNA-4485 ameliorates severe influenza pneumonia via inhibition of the STAT3/PI3K/AKT signaling pathway.

The present study aimed to explore the potential roles and mechanism of microRNA-4485 (miR-4485) in severe influenza pneumonia. miR-4485 expression was detected in patients with severe H1N1 pneumonia using quantitative PCR. Furthermore, the effects of aberrantly expressed miR-4485 on H1N1-infected A549 cells were investigated using Cell Counting Kit-8, terminal deoxynucleotidyl transferase dUTP nick end labeling, western blotting and (ELISA) assays. Furthermore, the regulatory relationships between miR-4485 and the STAT3-mediated PI3K/AKT/mTOR signaling pathway were explored using a luciferase reporter and rescue assay. MiR-4485 expression was downregulated following H1N1 infection and in patients with H1N1 pneumonia. In addition, miR-4485 alleviated H1N1-induced A549 cell injury by promoting cell viability and the production of cytokines, as well as reducing apoptosis in A549 cells. Furthermore, STAT3 was revealed to be a target gene of miR-4485. Additionally, STAT3 silencing reversed the protective effects of miR-4485 knockdown on H1N1-induced cell injury via inhibition of the PI3K/AKT/mTOR signaling pathway. In conclusion, miR-4485 inhibited H1N1-induced severe pneumonia in A549 cells by targeting STAT3 via the PI3K/AKT/mTOR signaling pathway.

Circular RNA circ_0001105 protects the intestinal barrier of septic rats by inhibiting inflammation and oxidative damage and YAP1 expression.

The integrity of the intestinal barrier is critical for protecting the host against the intestinal lumen and pathogens. The roles of circRNAs in the intestinal barrier dysfunction in sepsis remained unclear. The present study aims to investigate the role of circ_0001105 in the intestinal mucosal permeability, oxidative damage and morphological changes during sepsis. We found that upregulation of circ_0001105 decreased the levels of serum D-lactic acid, diamine oxidase and fluorescence isothiocyanate dextran in septic rats. Upregulation of circ_0001105 also decreased the malondialdehyde content but enhanced superoxide dismutase activity in the intestinal tissues. Upregulation of circ_0001105 reduced the production of tumor necrosis factor α, interleukin (IL)-6, and IL-1ß and the expression of YAP1. Furthermore, upregulation of circ_0001105 improved the survival of rats with sepsis. In summary, our findings showed that circ_0001105 protects the intestinal barrier function of septic rats by inhibiting intestinal inflammation, oxidative damage and YAP1 expression. Our results provide a novel insight for developing sepsis treatment.

Nickel-Catalyzed Reductive 1,2-Dialkynylation of Alkenes Bearing an 8-Aminoquinoline Directing Group.

An unprecedented nickel-catalyzed reductive 1,2-dialkynylation of alkenes bearing an 8-aminoquinoline directing group has been developed. This method proceeded through a migratory insertion/reductive-coupling process under mild conditions with a wide substrate scope and good functional group tolerance, providing direct access to the synthetically flexible 1,5-diynes. Moreover, the 1,2-dialkynylation products could be further converted to borate-ester- or azide-functionalized 1,5-dienes, ditriazole, ß-diyne primary amide, and trisubstituted benzene.

Comparison of urinary TIMP-2 and IGFBP7 cut-offs to predict acute kidney injury in critically ill patients: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are recently identified urinary biomarkers of acute kidney injury (AKI) in critically ill patients. Because their predictive accuracies vary widely, a meta-analysis was performed to evaluate the accuracy of previously reported urinary TIMP-2 and IGFBP7 cut-offs for predicting AKI. METHODS: This meta-analysis was reported following the guideline of PRISMA. Four databases, PubMed, the Cochrane Library, the ISI Web of Knowledge, and Embase, were systematically searched from inception to June 2018 by 2 investigators, who independently selected studies, extracted relevant data, and evaluated study quality. A bivariate model was used to calculate the pooled estimates. RESULTS: The search identified 5 studies with 1619 critically ill patients. Urinary TIMP-2 and IGFBP7 cut-off points of 0.3 (ng/ml)/1000 had a sensitivity of 0.89 [95% confidence interval (CI) 0.85-0.93], a specificity of 0.48 (95% CI 0.45-0.51) and a diagnostic odds ratio (DOR) of 8.33 (95% CI 5.55-12.52). The area under the curve (AUC) estimated by the summary receiver operating characteristic (SROC) curve was 0.748. Based on 891 critically ill patients from 4 studies, urinary TIMP-2 and IGFBP7 cut-off points of 2.0 (ng/ml)/1000 had a sensitivity of 0.45 (95% CI 0.37-0.53), a specificity of 0.93 (95% CI 0.91-0.95) and a DOR of 11.43 (95% CI 7.43-17.57). The AUC estimated by SROC was 0.844. CONCLUSION: Cut-off values around 0.3 (ng/ml)/1000 (high sensitivity) and 2.0 (ng/ml)/1000 (high specificity) could be accurate surrogate biomarkers predicting AKI in critically ill patients. The urinary TIMP-2 and IGFBP7 cut-off point of 2.0 (ng/mL)/1000 appears to have the highest overall accuracy. TRIAL REGISTRATION: PROSPERO registration number 2018: CRD42018084457 Registered on 11 February 2018.

Clinical efficacy of nutrition support therapy combined with antibiotics in the patients of community-acquired pneumonia and its influence on serum pct and crp.

To analyze the clinical efficacy of nutrition support therapy combined with antibiotics in the treatment of patients with ICU severe community-acquired pneumonia and its effect on serum procalcitonin (PCT) and C reactive protein (CRP). A total of 90 patients with ICU severe community-acquired pneumonia treated in hospital from September 2016 to June 2017.The patients were randomly divided into A group and B group 45 cases in each group. Both groups were given antibiotic treatment of azithromycin plus cefuroxime sodium in which the A group received enteral nutrition support therapy while the B group parenteral nutritional support therapy. Levels of serum prealbumin (PA), albumin (ALB), transferrin (TF), procalcitonin (PCT) and C reactive protein (CRP) before and after treatment were compared. Before treatment there was found no significant difference in serum PA, ALB and TF levels (p>0.05) while after treatment, the serum levels of PA, ALB and TF in the A group were significantly higher than those in the B group (p<0.05). The effective rate of the A group was 88.9%, higher than that of the B group (p<0.05). In patients with ICU severe community-acquired pneumonia, the treatment of enteral nutrition support therapy combined with antibacterial drugs of azithromycin and cefuroxime sodium can effectively improve the indexes of PA, ALB and TF. The reduce levels of serum PCT and CRP with the good prognosis is important in popularization and application in clinical practices.

Clinical Features and Prognostic Factors in Elderly Ewing Sarcoma Patients.

BACKGROUND Elderly patients with Ewing sarcoma have a very poor prognosis, and treatment remains a challenge. However, the outcomes and potential prognostic factors of elderly Ewing sarcoma patients are rarely documented. Therefore, we investigated the prognosis of this special cohort and determine independent prognostic factors. MATERIAL AND METHODS A cohort of Ewing sarcoma patients aged over 40 years from 1973 to 2015 was identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method and a Cox proportional hazard regression model were used for the prognostic analysis. RESULTS A total of 162 patients were included with a mean age of 53 years. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates of the entire group were 43.7% and 47.9%, respectively. The sex, location, tumor size, and radiation treatment had no effect on survival outcomes on univariate analysis. Tumor stage, surgery, and chemotherapy were significant indicators of both OS and CSS on multivariable analysis. CONCLUSIONS Surgery in combination with chemotherapy had a significant survival benefit in elderly Ewing sarcoma patients and should be recommended.

[Visualization studies on research status of the ventilator-associated pneumonia based on SinoMed database].

OBJECTIVE: To survey the distribution pattern and subject domain knowledge of the literatures about ventilator-associated pneumonia (VAP). METHODS: Literatures about VAP published until December 2017 were identified in SinoMed database for statistics and analysis. The information of author, organization and province was extracted by BICOMS software for generating co-occurrence matrix, at the same time, the topic words were cluster analyzed by Gcluto software to generate topical visual surface maps and visualization matrices, and the current research hotspots were analyzed. NetDraw from Ucinet 6.0 software was used to arrange the relationship among topic words according to the centrality, and the social network diagrams of authors, authors' provinces and institutions were draw to analyze the current status of VAP research cooperation. RESULTS: 4 851 VAP-related literatures were retrieved preliminarily, and 43 were excluded from abstracts, news reports, information and missing literatures. Finally, a total of 4 808 articles were enrolled in the visual analysis. From 2001 to 2004, the number of VAP-related literatures published was less than 10. Since 2009, the number of VAP documents had increased steadily, from 2010 to 2017, the peak period of publications reached 91.7% (4 411/4 808). According to the analysis of the amount of publications, the top three of 34 provincial administrative regions that published VAP-related literature in China were Guangdong Province (n = 628), Jiangsu Province (n = 478) and Zhejiang Province (n = 404), the number of hospitals issued by the First Affiliated Hospital of Chongqing Medical University was the largest (n = 20); there was only one journal with more than 100 articles, and there were 154 journals with only one article, accounting for 34.8% of the total number of journals. A total of 9 921 authors participated in the VAP-related literature writing, the number of high-yielding authors was not large, and the institution could not establish an effective social network diagram, suggesting that communication and cooperation should be strengthened in hospitals and outside hospitals. The results of the topic words social network analysis showed that the VAP research field was centered around the core of "mechanical ventilation", "intensive care unit (ICU)", "risk factor analysis", "nursing", "etiological analysis", "preventive measures" and "pathogens". The current research hotspots were at the edge of the network map, such as "drug sensitivity analysis", "Acinetobacter baumannii", "bronohoalveolar lavage (BAL)" and "acute exacerbation of chronic obstructive pulmonary disease (AECOPD)". By clustering 80 high-frequency topic words, at present, VAP research hotspots were mainly focus on five topics: obstructive pulmonary disease, especially in acute exacerbation, was prone to VAP; concerned about newborns and children's VAP; types, drug resistance and selection of antimicrobial agents for VAP pathogens in ICU; clinical efficacy and prognosis of VAP through preventive measures, pulmonary supportive care and comprehensive care interventions; oral care and airway management during mechanical ventilation was also the key aspect of the treatment of VAP. CONCLUSIONS: In recent years, the academics had attached great importance to the study of VAP, the number of publications had reached a historical peak, and the research direction was diverse. However, it was necessary to strengthen cooperation among research institutes, collect and count epidemiological data, improve and expand the research quality and scale of clinical diagnosis, nurse, prevention, pathogen distribution and drug resistance analysis.

Carapax Trionycis extracts inhibit fibrogenesis of activated hepatic stellate cells via TGF-ß1/Smad and NFκB signaling.

Carapax Trionycis is used as a traditional Chinese medicine with a long history of clinical application in China, and it represents an essential medication used for liver fibrosis treatment. Previous studies demonstrated that Carapax Trionycis extracts protect liver against fibrosis in CCL4-induced animal models. This study investigated the anti-fibrotic molecular mechanisms exerted by Carapax Trionycis extracts with molecular weight less than 6 KD (CT6) in rat hepatic stellate cell line HSC-T6 activated by TGF-ß1. HSC-T6 cells induced by TGF-ß1 were used to evaluate CT6 anti-fibrotic effect in vitro. CCK8 was used to evaluate cell viability and CT6 effect on HSC-T6 proliferation. ELISA was performed to detect the presence of inflammatory cytokines. Western blot and q-PCR were performed to explore the molecular mechanisms. Our data demonstrated that CT6 did not clearly affect cell viability but suppressed TGF-ß1-induced HSC-T6 proliferation. Collagen I and α-smooth muscle actin (α-SMA) protein levels were decreased by CT6 in TGF-ß1-induced HSC-T6, followed by the inhibition of TIMP1, TIMP2 and TGF-ß1/Smad pathway. Furthermore, CT6 decreased Jun D and p-p65 protein levels, down-regulated Tgf-ß1, Tnf-α, Il-1ß, Il-6 mRNA and TNF-α, IL-1ß and IL-6 expression in TGF-ß1-treated HSC-T6. These results suggested that CT6 inhibited HSC-T6 activation induced by TGF-ß1, indicating the potential therapeutic effect of these extracts against liver fibrosis.

[Treatment of thoracolumbar burst fracture with subtotal vertebrectomy, decompression and strut grafting through posterolateral approach].

OBJECTIVE: To explore the clinical effect of subtotal vertebrectomy, decompression and strut grafting in treating thoracolumbar burst fractures through posterolateral approach via posterior midline incision. METHODS: From May 2005 to July 2008, 14 patients with thoracolumbar burst fractures were treated with subtotal vertebrectomy, decompression and strut grafting through posterolateral approach via posterior midline incision. There were 9 males and 5 females, ranging in age from 24 to 68 years, with an average of 42.3 years. All patients were single segment fractures, of them, T11 was in 1 case, T12 in 5, L1 in 5 and L2 in 3. According to AO classification in spinal fracture, type A3 was in 5 cases, B1 in 3, B2 in 3, C1 in 2, C2 in 1. According to the ASIA classification in neurological function, grade A was in 3 cases, B in 3, C in 5, D in 2, E in 1. The height of anterior border vertebral body, volume of spinal canal and neurological function were analyzed by X-ray films, CT scanning and ASIA classification preoperative, postoperative and at final follow-up. RESULTS: Operative time was from 3.5 to 5.5 hours with the mean of 4.0 hours; bleeding during operation was from 800 to 2 600 ml with the mean of 1 300 ml. Two cases with nerve root injury recovered without special handling after 3-6 months; 1 case with leakage of cerebrospinal fluid restored through lumbar cerebrospinal fluid drainage; 1 case with pleura tear healed through closed thoracic drainage. No iatrogenic vascular injury or infection was found. The follow-up time was from 8 to 36 months with the mean of 16.5 months. All patients had neurofunctional recovery at different degree, except that 3 patients in grade A. The height of anterior border vetebral body restored from (42.25 +/- 11.87)% preoperatively to (94.38 +/- 3.08)% postoperatively, and (92.87 +/- 3.32)% at final follow-up (P<0.05); volume of spinal canal (the actual volume of spinal canal/normal volume of spine canal) increased from (45.63 +/- 6.88)% preoperatively to (95.26 +/- 3.31)% postoperatively, and (96.13 +/- 2.56)% at final follow-up (P<0.05). Cobb angle were corrected from (25.64 +/- 4.40) degrees preoperatively to (5.80 +/- 1.14) degrees postoperatively; Cobb angle lost from 0 degrees to 6 degrees at final follow-up with (8.10 +/- 2.65) degrees. All patients obtained complete bony fusion without pseudarthrosis formation at final follow-up. CONCLUSION: Subtotal vertebrectomy decompression and strut grafting through posterolateral approach via posterior midline incision is an effective and safe method in treating thoracolumbar burst fracture, which can restored height of intervertebral body, volume of spinal canal and physiological flexion of spinal column, and retain spinal permanent stability.