Publications by authors named "Xiaoli Huang"

198 Publications

Cytoplasmic tail truncation of SARS-CoV-2 Spike protein enhances titer of pseudotyped vectors but masks the effect of the D614G mutation.

J Virol 2021 Sep 8:JVI0096621. Epub 2021 Sep 8.

Department of Molecular Microbiology and Immunology, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.

The high pathogenicity of SARS-CoV-2 requires it to be handled under biosafety level 3 conditions. Consequently, Spike protein pseudotyped vectors are a useful tool to study viral entry and its inhibition, with retroviral, lentiviral (LV) and vesicular stomatitis virus (VSV) vectors the most commonly used systems. Methods to increase the titer of such vectors commonly include concentration by ultracentrifugation and truncation of the Spike protein cytoplasmic tail. However, limited studies have examined whether such a modification also impacts the protein's function. Here, we optimized concentration methods for SARS-CoV-2 Spike pseudotyped VSV vectors, finding that tangential flow filtration produced vectors with more consistent titers than ultracentrifugation. We also examined the impact of Spike tail truncation on transduction of various cell types and sensitivity to convalescent serum neutralization. We found that tail truncation increased Spike incorporation into both LV and VSV vectors and resulted in enhanced titers, but had no impact on sensitivity to convalescent serum inhibition. In addition, we analyzed the effect of the D614G mutation, which became a dominant SARS-CoV-2 variant early in the pandemic. Our studies revealed that, similar to the tail truncation, D614G independently increases Spike incorporation and vector titers, but that this effect is masked by also including the cytoplasmic tail truncation. Therefore, the use of full-length Spike protein, combined with tangential flow filtration, is recommended as a method to generate high titer pseudotyped vectors that retain native Spike protein functions. Pseudotyped viral vectors are useful tools to study the properties of viral fusion proteins, especially those from highly pathogenic viruses. The Spike protein of SARS-CoV-2 has been investigated using pseudotyped lentiviral and VSV vector systems, where truncation of its cytoplasmic tail is commonly used to enhance Spike incorporation into vectors and to increase the titers of the resulting vectors. However, our studies have shown that such effects can also mask the phenotype of the D614G mutation in the ectodomain of the protein, which was a dominant variant arising early in the COVID-19 pandemic. To better ensure the authenticity of Spike protein phenotypes when using pseudotyped vectors, we recommend using full-length Spike proteins, combined with tangential flow filtration methods of concentration if higher titer vectors are required.
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http://dx.doi.org/10.1128/JVI.00966-21DOI Listing
September 2021

Microbial analysis reveals the potential colonization of pathogens in the intestine of crayfish (Procambarus clarkii) in traditional aquaculture environments.

Ecotoxicol Environ Saf 2021 Aug 25;224:112705. Epub 2021 Aug 25.

Institute of Fisheries Research, Chengdu Academy of Agricultural and Forestry Sciences, Wenjiang 611130, Sichuan, China. Electronic address:

The microbiota of the intestine produces a wide array of biologically active molecules and together act as a composite endocrine organ. Due to our limited understanding of bacterial communities in aquaculture ecosystems, it is necessary to evaluate the interactions between environmental and intestinal microbiota and the potential consequences of disease. This study taken the traditional P. clarkii culture in the Sichuan Basin as an example, and analyzed the relationships between the microbiota of the environment and host through microbial analysis and microbiological diagnosis. Our results showed that the bacterial abundance in sediment was greater than in water, followed by the intestine, and some of bacteria from the environment successfully selected to colonize the intestine. The bacterial composition in the intestines of diseased and healthy crayfish was significantly different. The bacteria that colonized and proliferated in the intestine had very low abundances in sediment and water. Two potential pathogens, Aeromonas veronii, and Citrobacter freundii, and two potential probiotics, Lactococcus garvieae and Exiguobacterium undae, were identified. Using multiple, real, and traditional P. clarkii aquaculture sites in the Sichuan Basin, this study revealed that the microbial communities of the environment and animal host did indeed interact. Furthermore, these results indicated that P. clarkii in a healthy status are capable of regulating which bacteria colonize their intestines.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112705DOI Listing
August 2021

Purification of Ethyl Linoleate from Foxtail Millet () Bran Oil via Urea Complexation and Molecular Distillation.

Foods 2021 Aug 19;10(8). Epub 2021 Aug 19.

College of Food Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), No. 3501 Daxue Road, Changqing District, Jinan 250353, China.

Foxtail millet () bran oil is rich in linoleic acid, which accounts for more than 60% of its lipids. Ethyl linoleate (ELA) is a commercially valuable compound with many positive health effects. Here, we optimized two ELA processing steps, urea complexation (UC) and molecular distillation (MD), using single-factor and response surface analyses. We aimed to obtain a highly concentrated ELA at levels that are permitted by current regulations. We identified the optimal conditions as follows: 95% ethanol-to-urea ratio = 15:1 (/), urea-to-fatty acid ratio = 2.5:1 (/), crystallization time = 15 h, and crystallization temperature = -6 °C. Under these optimal UC conditions, ELA concentration reached 45.06%. The optimal MD purification conditions were established as follows: distillation temperature = 145 °C and vacuum pressure = 1.0-5.0 × 10 mbar. Under these conditions, ELA purity increased to 60.45%. Together, UC and MD were effective in improving the total concentration of ELA in the final product. This work shows the best conditions for separating and purifying ELA from foxtail millet bran oil by UC and MD.
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http://dx.doi.org/10.3390/foods10081925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392090PMC
August 2021

O-GlcNAc transferase Ogt regulates embryonic neuronal development through modulating Wnt/β-catenin signaling.

Hum Mol Genet 2021 Aug 4. Epub 2021 Aug 4.

The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China.

Ogt-mediated O-GlcNAcylation is enriched in the nervous system, and involves in neuronal development, brain function and neurological diseases. However, the roles of Ogt and O-GlcNAcylation in embryonic neurogenesis has remained largely unknown. Here, we show that Ogt is highly expressed in embryonic brain, and Ogt depletion reduces the proliferation of embryonic neural stem cells and migration of new born neurons. Furthermore, Ogt in cultured hippocampal neurons impaires neuronal maturation including reduced dendritic numbers and length, and immature development of spines. Mechanistically, Ogt depletion decreases the activity of Wnt/β-catenin signaling. Ectopic β-catenin rescues neuronal developmental deficits caused by Ogt depletion. Ogt also regulates human cortical neurogenesis in forebrain organoids derived from induced pluripotent stem cells. Our findings reveal the essential roles and mechanisms of Ogt-mediated O-GlcNAc modification in regulating mammalian neuronal development.
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http://dx.doi.org/10.1093/hmg/ddab223DOI Listing
August 2021

A High Starch Diet Alters the Composition of the Intestinal Microbiota of Largemouth Bass , Which May Be Associated With the Development of Enteritis.

Front Microbiol 2021 8;12:696588. Epub 2021 Jul 8.

Department of Aquaculture, College of Animal Science & Technology, Sichuan Agricultural University, Chengdu, China.

Starch is an inexpensive feed ingredient that has been widely used in fish feed. However, starch utilization by carnivorous fish is limited and excess starch is detrimental to the health of the organism. High starch diets often lead to liver damage, but the effects on the intestine are often overlooked. Therefore, in this study, two isonitrogenous and isolipidic semi-pure diets (NC: 0% α-starch, HC: 22% α-starch) were formulated and fed to largemouth bass ( for 45 days. The effects of the high starch diet on the intestine of largemouth bass were comprehensively investigated by intestinal microbiota, histopathology, ultrastructural pathology, and enzymology analyses. Feeding the HC diet did not affect the growth of largemouth bass during the experimental period. However, the high starch diet led to a reduction in the diversity and abundance of intestinal microbiota in largemouth bass, with a significant increase in the abundance of harmful bacteria () and a decrease in the abundance of beneficial bacteria (, , and ). Feeding the HC diet caused the development of enteritis, with goblet cell hyperplasia, epithelial necrosis and detachment and inflammatory cell infiltration, and leading to enlarged apical openings and mitochondrial damage in goblet cells. Long-term feeding of the HC diet inhibited intestinal α-amylase activity. changes in the intestinal microbiota, such as an increase in and a decrease in , , and , may be closely related to the development of enteritis. Therefore, adding these beneficial bacteria as probiotics may be an effective way to prevent damage to the intestine of largemouth bass from a high carbohydrate diet. Our results suggest reducing the amount of starch added to the largemouth bass diets. This study provides a reference for protecting the largemouth bass gut during modern intensive culture.
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http://dx.doi.org/10.3389/fmicb.2021.696588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297414PMC
July 2021

Salidroside activates the AMP-activated protein kinase pathway to suppress non-alcoholic steatohepatitis.

Hepatology 2021 Jul 22. Epub 2021 Jul 22.

Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.

Background & Aims: Nonalcoholic steatohepatitis (NASH) is becoming a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC). Salidroside (p-hydroxyphenethyl-β-d-glucoside) has various biological and pharmacological activities, including anti-inflammatory, antioxidant and anticancer activities. However, the therapeutic effect and underlying molecular mechanism of salidroside in NASH remain to be further clarified.

Methods & Results: In this study, we found that salidroside alleviated lipid accumulation and inflammatory response in primary hepatocytes after palmitic acid/oleic acid (PO) stimulation. In addition, salidroside effectively prevented high-fat/high-cholesterol (HFHC) diet induced NASH progression by regulating glucose metabolism dysregulation, insulin resistance, lipid accumulation, inflammation and fibrosis. Mechanistically, integrated RNA sequencing and bioinformatic analysis showed that salidroside promoted AMPK signaling pathway activation in vitro and in vivo, and this finding was further verified by determining the phosphorylation levels of AMPK. Furthermore, the protective effects of salidroside on lipid accumulation and inflammation in hepatocytes and livers induced by PO- or HFHC- stimulation were blocked by AMPK interruption.

Conclusion: Our studies demonstrate that salidroside protects against metabolic stress-induced NASH progression through activation of AMPK signaling, indicating that salidroside could be a potential new drug component for NASH therapy.
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http://dx.doi.org/10.1002/hep.32066DOI Listing
July 2021

The potential risk of antibiotic resistance of Streptococcus iniae in sturgeon cultivation in Sichuan, China.

Environ Sci Pollut Res Int 2021 Jul 21. Epub 2021 Jul 21.

College of Veterinary Medicine, Sichuan Agricultural University, Huimin Road No. 211, Wenjiang, Chengdu, Sichuan, 611130, People's Republic of China.

Sichuan, located in the upper reaches of the Yangtze River, is the gathering place of many rivers and plays an important role in sturgeon aquaculture and wild sturgeon protection in China, where it suffered the severe influence of Streptococcus iniae infection in sturgeon. However, the annual thousands of tons of antibiotic usage in Sichuan may accumulate in water and cause obstacles to the prevention of S. iniae infection. In contrast, the regional antibiotic resistance characteristics have been rarely unknown. Seventeen S. iniae strains were collected from the major sturgeon culture areas in Sichuan, and the genotyping and the distribution of antibiotic resistance profiles (ARPs) and genes (ARGs) of S. iniae were established in this study. The results showed that the isolates could be divided into four subtypes by pulsed-field gel electrophoresis analysis. Besides, most isolates showed multiple resistance to the antibiotic such as amikacin, neomycin, enrofloxacin, lincomycin, and sulfamethoxazole. Also, sturgeon-derived S. iniae has a relatively low similarity with other fish-derived S. iniae in the world but high similarity with three animal-derived pathogens from Sichuan in previous studies. Moreover, a total of 37 ARGs were detected positively based on 95 ARGs detection, in which aac(6')-Ib(aka aacA4)-01, aac(6')-Ib(aka aacA4)-02, aadA1, floR, blaTEM, sulA/folP-03, and tetA-02 were most prevalent. Our study indicated that the ARGs of sturgeon-derived S. iniae were significantly enhanced compared with the ATCC29178 strains and have a risk of accessing more ARGs from other bacteria in water in Sichuan. This study claimed that sturgeon has a potential risk in the prevention and control of Streptococcosis in Sichuan, the upper reaches of Yangtze River, based on the antibiotic resistance analysis of S. iniae, and it may also increase the risk of highly resistant S. iniae transmission into the middle and lower reaches.
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http://dx.doi.org/10.1007/s11356-021-15501-1DOI Listing
July 2021

Differences in Manifestations and Gut Microbiota Composition Between Patients With Different Henoch-Schonlein Purpura Phenotypes.

Front Cell Infect Microbiol 2021 1;11:641997. Epub 2021 Jul 1.

Department of Pediatrics, Fujian Medical University Union Hospital, Fuzhou, China.

Background: Gut microbiota plays an important role in the pathogenesis of immune-mediated diseases. However, the complex pathogenesis of Henoch-Schonlein Purpura (HSP) remains elusive. This study aimed to characterize the gut microbiota in HSP patients and explore the potential association between gut microbiota composition and phenotypic changes in HSP.

Methods: 16SrRNA gene sequencing and bioinformatic analyses were performed using total DNA extracted from the fecal microbiota of 34 children with HSP, including 18 primary cases, 16 recurrent cases, and 23 healthy children.

Results: The diversity indexes showed significant differences in the microbial community among the primary HSP groups, the recurrent HSP group and healthy controls. The abundance of in the recurrent HSP group was significantly higher than that in the primary HSP group, and the constructed ROC curve had an AUC value of 0.750. According to the Spearman correlation analysis, the abundance of was positively associated with the serum IgG level in children with HSP, while the abundance of was negatively correlated with the complement component 3 (C3). The diversity indexes of gut microbiota in the HSP group with abdominal symptoms were higher than those in the HSP group without GI involvement, and also higher than those in the healthy control group. In the HSP group with GI involvement, the abundance of was decreased, while the abundance of and was increased, compared to the HSP group without GI involvement.

Conclusions: The gut microbiota of children with HSP was different from that of healthy children. The genus has a diagnostic value for HSP recurrence. and may affect IgG and complement C3 levels in children with HSP. Abdominal symptoms in HSP children were related to gut microbiota ( and butyric acid-producing bacteria).
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http://dx.doi.org/10.3389/fcimb.2021.641997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8281929PMC
July 2021

Selective Inhibition of the Second Bromodomain of BET Family Proteins Results in Robust Antitumor Activity in Preclinical Models of Acute Myeloid Leukemia.

Mol Cancer Ther 2021 Jul 12. Epub 2021 Jul 12.

Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Dual bromodomain BET inhibitors that bind with similar affinities to the first and second bromodomains across BRD2, BRD3, BRD4, and BRDT have displayed modest activity as monotherapy in clinical trials. Thrombocytopenia, closely followed by symptoms characteristic of gastrointestinal toxicity, have presented as dose-limiting adverse events that may have prevented escalation to higher dose levels required for more robust efficacy. ABBV-744 is a highly selective inhibitor for the second bromodomain of the four BET family proteins. In contrast to the broad antiproliferative activities observed with dual bromodomain BET inhibitors, ABBV-744 displayed significant antiproliferative activities largely although not exclusively in cancer cell lines derived from acute myeloid leukemia and androgen receptor positive prostate cancer. Studies in acute myeloid leukemia xenograft models demonstrated antitumor efficacy for ABBV-744 that was comparable with the pan-BET inhibitor ABBV-075 but with an improved therapeutic index. Enhanced antitumor efficacy was also observed with the combination of ABBV-744 and the BCL-2 inhibitor, venetoclax compared with monotherapies of either agent alone. These results collectively support the clinical evaluation of ABBV-744 in AML (Clinical Trials.gov identifier: NCT03360006).
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http://dx.doi.org/10.1158/1535-7163.MCT-21-0029DOI Listing
July 2021

Clinical Characteristics of Paracentral Acute Middle Maculopathy in Eyes with Retinal Vascular Occlusion Diseases in Chinese Patients.

J Ophthalmol 2021 18;2021:8867570. Epub 2021 Jun 18.

Department of Ophthalmology, Shanghai General Hospital of Nanjing Medical University, Shanghai, China.

Aim: To investigate the incidence and clinical characteristics of paracentral acute middle maculopathy (PAMM) and its relationship with prominent middle limiting membrane (p-MLM) sign in eyes with retinal artery occlusion (RAO) or retinal vein occlusion (RVO) in a Chinese clinical setting.

Methods: In this retrospective observational study from January 2015 to May 2020, multimodal imaging data of 807 eyes including 555 consecutive patients with RVO or 252 consecutive patients with RAO were reviewed. All patients were scanned using the spectrum-domain optical coherence tomography (OCT), and some of them underwent color fundus photography, fundus fluorescence angiography, en face OCT, and OCT angiography.

Results: PAMM was detected in 49 eyes of 49 RAO patients and 29 eyes of 29 RVO patients. The mean ages at presentation were 64.49 ± 13.90 years and 54.00 ± 18.48 years in RAO and RVO patients (=0.006), respectively. Eyes with RAO were more prone to develop PAMM (19.44% [49/252] vs. 5.23% [29/555]; < 0.001). Of the 78 eyes with PAMM, 24 eyes (7 eyes with RVO and 17 eyes with RAO) were found with p-MLM sign. An interesting phenomenon that had been overlooked before was that the hyperreflective line of the p-MLM sign was usually continuous, regardless of the type of PAMM lesion.

Conclusions: This series is the largest to date to describe the clinical characteristics of PAMM and p-MLM sign in Chinese patients. The incidence of PAMM and p-MLM sign in patients with RAO was relatively higher than that in patients with RVO. These signs alone probably represent milder ischemia and prompt us to carry out a comprehensive and meticulous examination to prevent the further development of the disease. In addition, the hyperreflective line of the p-MLM sign was usually continuous, which could support the totally venous nature of the retinal deep capillary plexus to some extent.
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http://dx.doi.org/10.1155/2021/8867570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235965PMC
June 2021

Breast cancer cell line toxicity of a flavonoid isolated from Baccharis densiflora.

BMC Complement Med Ther 2021 Jul 2;21(1):188. Epub 2021 Jul 2.

Department of Biology, Lund University, Lund, Sweden.

Background: Flavonoids are compounds of interest in the search for new anti-cancer therapies. We have previously isolated the methoxyflavones 5,4'-dihydroxy-6,7,8,3'-tetramethoxyflavone (8-methoxycirsilineol), 5,4'-dihydroxy-6,7,8-trimethoxyflavone (xanthomicrol), and 5,4,'3'-trihydroxy-6,7,8-trimethoxyflavone (sideritoflavone) from Baccharis densiflora. Herein, we investigate the toxicity of these methoxyflavones in human breast-derived cell line. Our main aim was to focus on the cancer stem cell (CSC) sub-population of JIMT-1 breast cancer cells.

Methods: Initially, dose response experiments yielding inhibitory concentration 50 (IC) values were performed using MCF-7, HCC1937, and JIMT-1 breast cancer, and the MCF-10A normal-like breast cell lines to get an understanding of toxic ranges. Due to a clear difference in the toxicity of the flavones, only sideritoflavone was selected for further studies using the JIMT-1 cell line. Effects on the CSC sub-population was investigated using flow cytometry-based methods. A wound healing assay and digital holographic microscopy were used to investigate effects on cell movement. A reporter assay was used to study effects on signal transduction pathways and Western blot for protein expression.

Results: The dose response data showed that 8-methoxycirsilineol was non-toxic at concentrations below 100 μM, that the IC of xanthomicrol was between 50 and 100 μM, while sideritoflavone was highly toxic with a single digit μM IC in all cell lines. Treatment of the JIMT-1 cells with 2 μM sideritoflavone did not selectively effect the CSC sub-population. Instead, sideritoflavone treatment inhibited the proliferation of both the non-CSC and the CSC sub-populations to the same extent. The inhibition of cell proliferation resulted in an accumulation of cells in the G phase of the cell cycle and the treated cells showed an increased level of γ-H2A histone family member X indicating DNA double strand breaks. Analysis of the effect of sideritoflavone treatment on signal transduction pathways showed activation of the Wnt, Myc/Max, and transforming growth factor-β pathways. The level of p65/nuclear factor kappa-light-chain-enhancer of activated Β cells was increased in sideritoflavone-treated cells. Cell movement was decreased by sideritoflavone treatment.

Conclusions: Altogether our data show that the methoxyflavone sideritoflavone has favourable anti-cancer effects that may be exploited for development to be used in combination with CSC specific compounds.
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http://dx.doi.org/10.1186/s12906-021-03349-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254278PMC
July 2021

Adiponectin protects obesity-related glomerulopathy by inhibiting ROS/NF-κB/NLRP3 inflammation pathway.

BMC Nephrol 2021 Jun 10;22(1):218. Epub 2021 Jun 10.

Department of Endocrinology, The Third Affiliated Hospital of Soochow University, No.185 Bureau Front Street, 213003, Changzhou City, China.

Background: Adiponectin is an adipocytokine that plays a key regulatory role in glucose and lipid metabolism in obesity. The prevalence of obesity has led to an increase in the incidence of obesity-related glomerulopathy (ORG). This study aimed to identify the protective role of adiponectin in ORG.

Methods: Small-interfering RNA (siRNA) against the gene encoding adiponectin was transfected into podocytes. The oxidative stress level was determined using a fluorometric assay. Apoptosis was analyzed by flow cytometry. The expressions of podocyte markers and pyrin domain containing protein 3 (NLRP3) inflammasome-related proteins were measured by qRT-PCR, immunohistochemistry, and Western blot.

Results: Podocytes treated with palmitic acid (PA) showed downregulated expressions of podocyte markers, increased apoptosis, upregulated levels of NLRP3 inflammasome-related proteins, increased production of inflammatory cytokines (IL-18 and IL-1β), and induced activation of NF-κB as compared to the vehicle-treated controls. Decreased adiponectin expression was observed in the serum samples from high fat diet (HFD)-fed mice. Decreased podocin expression and upregulated NLRP3 expression were observed in the kidney samples from high fat diet (HFD)-fed mice. Treatment with adiponectin or the NLRP3 inflammasome inhibitor, MCC950, protected cultured podocytes against podocyte apoptosis and inflammation. Treatment with adiponectin protected mouse kidney tissues against decreased podocin expression and upregulated NLRP3 expression. The knockout of adiponectin gene by siRNA increased ROS production, resulting in the activation of NLRP3 inflammasome and the phosphorylation of NF-κB in podocytes. Pyrrolidine dithiocarbamate, an NF-κB inhibitor, prevented adiponectin from ameliorating FFA-induced podocyte injury and NLRP3 activation.

Conclusions: Our study showed that adiponectin ameliorated PA-induced podocyte injury in vitro and HFD-induced injury in vivo via inhibiting the ROS/NF-κB/NLRP3 pathway. These data suggest the potential use of adiponectin for the prevention and treatment of ORG.
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http://dx.doi.org/10.1186/s12882-021-02391-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191043PMC
June 2021

Vitamin E succinate exerts anti-tumour effects on human cervical cancer cells via the CD47-SIRPɑ pathway both and .

J Cancer 2021 5;12(13):3877-3886. Epub 2021 May 5.

Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Vitamin E succinate (RRR-a-tocopheryl succinate, VES) acts as a potent agent for cancer therapy and has no toxic and side effects on normal tissue cells. However, the mechanism by which VES mediates the effects are not yet fully understood. Here, we hypothesised that VES mediates antitumour activity on human cervical cancer cells via the CD47-SIRPɑ pathway and . Results indicated that the human cervical cancer HeLa cells treated with VES were more efficiently engulfed by THP-1-derived macrophages. In response to VES, the protein expression of CD47 on cell membranes and the mRNA level of CD47 in different human cervical cancer cells significantly decreased. And the level of calreticulin (CRT) mRNA in the VES-treated cells increased. By contrast, CRT protein expression was not altered. miRNA-155, miRNA-133 and miRNA-326 were up-regulated in the VES-treated HeLa cells. Knocking down miRNA-155 and miRNA-133 by RNA interference increased CD47 protein expression in the VES-treated cells. efficacy was determined in BALB/C nude mice with HeLa xenografts. Results showed that VES reduced tumour growth, increased overall survival and inhibited CD47 in the tumour transcriptionally and translationally. Furthermore, inflammatory factors (TNF-α, IL-12, IFN-γ, IL-2 and IL-10) in the spleen were altered because of VES treatment. Our results suggest that VES-induced antitumour activity is coupled to the CD47-SIRPɑ pathway in human cervical HeLa cancer cells.
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http://dx.doi.org/10.7150/jca.52315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176246PMC
May 2021

Methodology for Comprehensive Detection of Pyroptosis.

Methods Mol Biol 2021 ;2255:149-157

College of Animal Science & Technology, Sichuan Agricultural University, Chengdu, Sichuan, China.

Pyroptosis is a new type of programmed cell death identified in recent years, which destroys the integrity of cell membranes by punching pores on them, resulting in cell lysis. Light- and dark-colored vesicles/pore-like structures on the membranes of pyroptotic cells are generally observed using light microscope, accompanied by cell swelling and cytoplasmic release. However, due to the release of the cell contents in both pyroptosis and necrosis, it is difficult to distinguish them solely by morphological characteristics. The mechanism of pyroptosis involves three major signaling pathways, all activating downstream gasdermin (GSDM) D and E, which results in the formation of pores (10-15 nm) on the cell membrane, while small cytoplasmic molecules such as interleukin (IL)-1 and IL-18 flow out from the pores and cause inflammation. The occurrence of pyroptosis can be determined by a combination of markers. These include cleavage of GSDM D and E, activation and release of IL-1β and IL-18, and activation of cysteinyl aspartate specific proteinase (caspase-1, -3, -4, -5, and -11). This chapter discusses several common methods to assist researchers in detecting pyroptosis.
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http://dx.doi.org/10.1007/978-1-0716-1162-3_13DOI Listing
June 2021

The association between ambient air pollution and birth defects in five major ethnic groups in Liuzhou, China.

BMC Pediatr 2021 05 14;21(1):232. Epub 2021 May 14.

Department of Population and Quantitative Health Sciences, Albert Sherman Center, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605, USA.

Background: Studies suggest that exposure to ambient air pollution during pregnancy may be associated with increased risks of birth defects (BDs), but conclusions have been inconsistent. This study describes the ethnic distribution of major BDs and examines the relationship between air pollution and BDs among different ethnic groups in Liuzhou city, China.

Methods: Surveillance data of infants born in 114 registered hospitals in Liuzhou in 2019 were analyzed to determine the epidemiology of BDs across five major ethnic groups. Concentrations of six air pollutants (PM2.5, PM10, SO2, CO, NO2, O3) were obtained from the Liuzhou Environmental Protection Bureau. Logistic regression was used to examine the associations between ambient air pollution exposure and risk of BDs.

Results: Among 32,549 infants, 635 infants had BDs, yielding a prevalence of 19.5 per 1000 perinatal infants. Dong ethnic group had the highest prevalence of BDs (2.59%), followed by Yao (2.57%), Miao (2.35%), Zhuang (2.07%), and Han (1.75%). Relative to the Han ethnic group, infants from Zhuang, Miao, Yao and Dong groups had lower risks of congenital heart disease, polydactyly, and hypospadias. The Zhuang ethnic group had higher risks of severe thalassemia, cleft lip and/or palate, and syndactyls. Overall BDs were positively correlated with air pollutants PM (aOR =1.14, 95% CI:1.12 ~ 2.43; aOR =1.51, 95% CI:1.13 ~ 2.03 for per 10μg/mg3 increment) and CO (aOR =1.36, 95% CI:1.14 ~ 2.48; aOR =1.75, 95% CI:1.02 ~ 3.61 for every 1 mg /m3 increment) in second and third month of pregnancy. SO was also significantly associated with BDs in the second month before the pregnancy (aOR = 1.31; 95% CI: 1.20 ~ 3.22) and third month of pregnancy (aOR =1.75; 95% CI:1.02 ~ 3.61). Congenital heart disease, polydactyl, cleft lip and/or palate were also significantly associated with PM, SO and CO exposures. However, no significant association was found between birth defects and O, PM and NO exposures (P > 0.05).

Conclusion: This study provides a comprehensive description of ethnic differences in BDs in Southwest China and broadens the evidence of the association between air pollution exposure during gestation and BDs.
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http://dx.doi.org/10.1186/s12887-021-02687-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120832PMC
May 2021

Wrinkle and near-resonance effects on the vibrational and electronic properties in compressed monolayer MoSe.

Phys Chem Chem Phys 2021 May 13;23(20):11709-11716. Epub 2021 May 13.

State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun, 130012, China.

Pressure has been considered as an effective technique to modulate the structural, electronic, and optical properties of transition metal dichalcogenide (TMDs) materials. Here, by performing in situ high pressure Raman, photoluminescence (PL) and absorption measurements, we systematically investigated the vibrational and electronic properties evolution of monolayer MoSe grown on a SiO/Si substrate under high pressure. When the pressure increased up to 4.84 GPa, an unexpected phonon mode at 367 cm appeared, which was identified as the Raman-inactive A'' mode and was activated under high pressure. Combined with the analysis of absorption spectroscopy, this phenomenon can be attributed to the pressure-induced wrinkle and near-resonance effects in compressed monolayer MoSe. Subsequently, A' split into two peaks after 7.44 GPa, providing further distinct evidence for the pressure-induced wrinkle effect in compressed monolayer MoSe. Moreover, this wrinkle effect can also lead to a rapid quenching of photoluminescence in monolayer MoSe. These results suggest that the substrate plays an important role in determining the vibrational and electronic properties of compressed monolayer MoSe, and can provide valuable information on the electronic and optoelectronic applications of monolayer MoSe under extreme conditions.
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http://dx.doi.org/10.1039/d0cp06283aDOI Listing
May 2021

Dietary isoleucine improved flesh quality, muscle antioxidant capacity, and muscle growth associated with AKT/TOR/S6K1 and AKT/FOXO3a signaling in hybrid bagrid catfish (Pelteobagrus vachelli♀ × Leiocassis longirostris♂).

J Anim Sci Biotechnol 2021 Apr 19;12(1):53. Epub 2021 Apr 19.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, 611130, China.

Background: Muscle is the complex and heterogeneous tissue, which comprises the primary edible part of the trunk of fish and mammals. Previous studies have shown that dietary isoleucine (Ile) exerts beneficial effects on growth in aquatic animals. However, there were limited studies regarding the benefits of Ile on fish muscle and their effects on flesh quality and muscle growth. Thus, this study was conducted to explore whether dietary Ile had affected flesh quality and muscle growth in hybrid bagrid catfish (Pelteobagrus vachelli♀ × Leiocassis longirostris♂).

Methods: A total of 630 hybrid fish, with an initial average body weight of 33.11 ± 0.09 g, were randomly allotted into seven experimental groups with three replicates each, and respectively fed seven diets with 5.0, 7.5, 10.0, 12.5, 15.0, 17.5, and 20.0 g Ile/kg diets for 8 weeks.

Results: In the present study, we demonstrated that Ile significantly: (1) increased muscle protein and lipid contents and the frequency distribution of myofibers with ≤ 20 μm and ≥ 50 μm of diameter; (2) improved pH value, shear force, cathepsin B and L activities, hydroxyproline content, resilience, cohesiveness, and decreased cooking loss, lactate content, hardness, springiness, gumminess, and chewiness; (3) decreased reactive oxygen species (ROS), malondialdehyde (MDA), and protein carbonyl (PC) contents, GCLC and Keap1 mRNA levels, and up-regulated CuZnSOD, CAT, GPX1a, GST, and Nrf2 mRNA levels; (4) up-regulated the insulin-like growth factor 1, 2 (IGF-1, IGF-2), insulin-like growth factor 1 receptor (IGF-1R), proliferating cell nuclear antigen (PCNA), Myf5, Myod, Myog, Mrf4, and MyHC mRNA levels, and decreased MSTN mRNA level; (5) increased muscle protein deposition by activating AKT-TOR-S6K1 and AKT-FOXO3a signaling pathways.

Conclusion: These results revealed that dietary Ile improved flesh quality, which might be due to increasing nutritional content, physicochemical, texture parameters, and antioxidant ability; promoting muscle growth by affecting myocytes hyperplasia and hypertrophy, and muscle protein deposition associated with protein synthesis and degradation signaling pathways. Finally, the quadratic regression analysis of chewiness, ROS, and protein contents against dietary Ile levels suggested that the optimal dietary Ile levels for hybrid bagrid catfish was estimated to be 14.19, 12.36, and 12.78 g/kg diet, corresponding to 36.59, 31.87, and 32.96 g/kg dietary protein, respectively.
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http://dx.doi.org/10.1186/s40104-021-00572-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054373PMC
April 2021

Integrin α10-Antibodies Reduce Glioblastoma Tumor Growth and Cell Migration.

Cancers (Basel) 2021 Mar 9;13(5). Epub 2021 Mar 9.

Xintela AB, Medicon Village, Scheeletorget 1, SE-223 81 Lund, Sweden.

Glioblastoma (GB) is the most common and the most aggressive form of brain tumor in adults, which currently lacks efficient treatment strategies. In this study, we investigated the therapeutic effect of function-blocking antibodies targeting integrin α10β1 on patient-derived-GB cell lines in vitro and in vivo. The in vitro studies demonstrated significant inhibiting effects of the integrin α10 antibodies on the adhesion, migration, proliferation, and sphere formation of GB cells. In a xenograft mouse model, the effect of the antibodies on tumor growth was investigated in luciferase-labeled and subcutaneously implanted GB cells. As demonstrated by in vivo imaging analysis and caliper measurements, the integrin α10-antibodies significantly suppressed GB tumor growth compared to control antibodies. Immunohistochemical analysis of the GB tumors showed lower expression of the proliferation marker Ki67 and an increased expression of cleaved caspase-3 after treatment with integrin α10 antibodies, further supporting a therapeutic effect. Our results suggest that function-blocking antibody targeting integrin α10β1 is a promising therapeutic strategy for the treatment of glioblastoma.
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http://dx.doi.org/10.3390/cancers13051184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980568PMC
March 2021

Braiding and All Quantum Operations with Majorana Modes in 1D.

Phys Rev Lett 2021 Mar;126(11):117701

Kavli Institute of Nanoscience, Delft University of Technology, 2628 CJ Delft, Netherlands.

We propose a scheme to perform braiding and all other unitary operations with Majorana modes in one dimension that, in contrast to previous proposals, is solely based on resonant manipulation involving the first excited state extended over the modes. The detection of the population of the excited state also enables initialization and read-out. We provide an elaborated illustration of the scheme with a concrete device.
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http://dx.doi.org/10.1103/PhysRevLett.126.117701DOI Listing
March 2021

Ogt controls neural stem/progenitor cell pool and adult neurogenesis through modulating Notch signaling.

Cell Rep 2021 Mar;34(13):108905

The Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China; The Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou 310029, China; National Clinical Research Center for Child Health, Hangzhou 310052, China; Zhejiang University Cancer Center, Zhejiang University, Hangzhou 310029, China. Electronic address:

Ogt catalyzed O-linked N-acetylglucosamine (O-GlcNAcylation, O-GlcNAc) plays an important function in diverse biological processes and diseases. However, the roles of Ogt in regulating neurogenesis remain largely unknown. Here, we show that Ogt deficiency or depletion in adult neural stem/progenitor cells (aNSPCs) leads to the diminishment of the aNSPC pool and aberrant neurogenesis and consequently impairs cognitive function in adult mice. RNA sequencing reveals that Ogt deficiency alters the transcription of genes relating to cell cycle, neurogenesis, and neuronal development. Mechanistic studies show that Ogt directly interacts with Notch1 and catalyzes the O-GlcNAc modification of Notch TM/ICD fragment. Decreased O-GlcNAc modification of TM/ICD increases the binding of E3 ubiquitin ligase Itch to TM/ICD and promotes its degradation. Itch knockdown rescues neurogenic defects induced by Ogt deficiency in vitro and in vivo. Our findings reveal the essential roles and mechanisms of Ogt and O-GlcNAc modification in regulating mammalian neurogenesis and cognition.
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http://dx.doi.org/10.1016/j.celrep.2021.108905DOI Listing
March 2021

Evaluation of pathology and environmental variables contributing to hepatopancreatic necrosis syndrome of Chinese mitten crab, Eriocheir sinensis.

Ecotoxicol Environ Saf 2021 Jun 25;215:112157. Epub 2021 Mar 25.

Department of Aquaculture, College of Animal Science & Technology, Sichuan Agricultural University, Wenjiang 611130, Sichuan, China. Electronic address:

Hepatopancreatic Necrosis Syndrome (HPNS) severely impacts the Chinese mitten crab (Eriocheir sinensis) industry. However, little knowledge of the aetiology and pathogenesis of the disease causes significant difficulties in its prevention and control. In this study, we conducted a pathological analysis of HPNS through time-integrated large-volume sampling, to clarify the disease characteristics and mechanism of HPNS-afflicted crabs; besides, animal models were constructed to verify the pathological diagnosis. The results showed that the hepatopancreas was the principal target organ of HPNS; multiple correspondence analysis revealed that the main histopathological characteristics included non-interstitial atrophic hepatopathy diseases such as hepatic tubule atrophy, dilated hepatic tubules, and hepatic tubule necrosis. Additionally, the muscles also showed signs of disease, including myofibre atrophy, necrosis, and inflammation. Ultrastructural studies showed prominent apoptosis and autophagy-like alterations in the hepatopancreas of HPNS-afflicted crabs. Further, the establishment of animal models revealed that the double variate stimulation of environmental variables such as abamectin/sewage with nutrition deficiency could result in HPNS-similar lesions. Based on these studies, we concluded that HPNS is a chronic hepatopancreas-initiated energy-consumed disease with a low likelihood of pathogen but a high probability of environment and nutrition.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112157DOI Listing
June 2021

A New Superconducting 3R-WS Phase at High Pressure.

J Phys Chem Lett 2021 Apr 26;12(13):3321-3327. Epub 2021 Mar 26.

State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun 130012, China.

High-pressure investigation has been shown to be of paramount significance for changing the conventional lattice or bringing fascinating properties, especially inducing superconducting phases. Here we studied the application of pressure to the recently synthesized 2M-WS with the record (8.8 K) among transition metal dichalcogenides (TMDs) at ambient pressure by electrical resistance investigations, synchrotron X-ray studies, and theoretical calculations. in the initial 2M-WS dropped from the maximum to become undetected, accompanied by a phase transition into a semiconductor, 3R-WS, at 15 GPa. The successive metallization and superconducting transitions in 3R-WS were observed at 48.8 GPa with ≈ 2.5 K. This is the first experimental case in which superconductivity has been realized in the 3R phase among TMDs. We propose that the degradation of superconductivity in 2M-WS and the reemergence of superconductivity in 3R-WS are mainly attributable to changes in the density of states near the Fermi surface driven by the interlayer coupling.
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http://dx.doi.org/10.1021/acs.jpclett.1c00312DOI Listing
April 2021

Case Report: Acute Retinal Necrosis after Intravitreal Ranibizumab for Exudative Macular Degeneration.

Optom Vis Sci 2021 03;98(3):206-211

Significance: Acute retinal necrosis (ARN) may occur after intravitreal ranibizumab (IVR) treatment for patients with exudative age-related macular degeneration (AMD). Awareness of this unusual but devastating complication after IVR is needed. Early identification may help provide timely antiviral treatment and prevent irreversible visual loss.

Purpose: This study aimed to report a case of ARN after IVR in a patient with exudative AMD.

Case Report: A 67-year-old male patient complained of blurred vision in his left eye for 1 month. The patient was diagnosed with exudative AMD after detailed ophthalmic clinical evaluations. He received IVR once in his left eye. Three days after IVR, he developed varicella-zoster virus-associated ARN, which was treated with systemic and intravitreal antiviral therapy. Because of progressive inflammation, the patient underwent 25G pars plana vitrectomy with silicone oil tamponade. Seven months later, the patient was administered intravitreal aflibercept once in his left eye. Three months after intravitreal aflibercept, he underwent removal of silicone oil, and retinal detachment occurred 2 weeks after the surgery because of low IOP, and the patient eventually discontinued treatment.

Conclusions: This study reports the first case of varicella-zoster virus-associated ARN after IVR. Early ARN may be very difficult to distinguish from intraocular inflammation after IVR. Therefore, early detection of viral DNA in the intraocular fluid using polymerase chain reaction is recommended. Immediate antiviral treatment may be beneficial to prevent severe visual loss.
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http://dx.doi.org/10.1097/OPX.0000000000001649DOI Listing
March 2021

Autolysis in Crustacean Tissues after Death: A Case Study Using the Hepatopancreas.

Biomed Res Int 2021 12;2021:2345878. Epub 2021 Jan 12.

Department of Aquaculture, College of Animal Science & Technology, Sichuan Agricultural University, Wenjiang Chengdu, 611130 Sichuan, China.

Autolysis is an internal phenomenon following the death of an organism that leads to the degradation of tissues. In order to explore the initial stages of autolysis and attempt to establish reference standards for tissue changes after death, we studied the rapidly autolyzing tissue of the crayfish hepatopancreas. Samples from the hepatopancreas of crayfish were examined 0, 5, 10, 30, 60, and 120 minutes after death. Histological and ultrapathological examinations and evaluations and apoptotic cell counts were conducted to determine the initiation time and degree of autolysis. The results showed that autolysis in the hepatopancreas of crayfish began within 5 minutes. Initially, autolysis manifested in the swelling of hepatic tubular cells and the widening of mesenchyme. Cells undergoing autolysis showed severe organelle necrolysis. Based on these observations, tissue samples should be collected and preserved within five minutes to avoid interfering with histopathological diagnoses.
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http://dx.doi.org/10.1155/2021/2345878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817300PMC
February 2021

CAP1, a target of miR-144/451, negatively regulates erythroid differentiation and enucleation.

J Cell Mol Med 2021 03 26;25(5):2377-2389. Epub 2021 Jan 26.

Department of Animal Sciences, College of Agriculture and Natural Resources, Michigan State University, East Lansing, MI, USA.

The exact molecular mechanism underlying erythroblast enucleation has been a fundamental biological question for decades. In this study, we found that miR-144/451 critically regulated erythroid differentiation and enucleation. We further identified CAP1, a G-actin-binding protein, as a direct target of miR-144/451 in these processes. During terminal erythropoiesis, CAP1 expression declines along with gradually increased miR-144/451 levels. Enforced CAP1 up-regulation inhibits the formation of contractile actin rings in erythroblasts and prevents their terminal differentiation and enucleation. Our findings reveal a negative regulatory role of CAP1 in miR-144/451-mediated erythropoiesis and thus shed light on how microRNAs fine-tune terminal erythroid development through regulating actin dynamics.
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http://dx.doi.org/10.1111/jcmm.16067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7933962PMC
March 2021

Infection-Induced Rhabdomyolysis in an Elderly Patient on Stable Rosuvastatin Therapy: A Case Report and Review of the Literature.

Am J Ther 2021 Jan 5. Epub 2021 Jan 5.

The Center of Gerontology and Geriatrics, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.

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http://dx.doi.org/10.1097/MJT.0000000000001325DOI Listing
January 2021

Synthesis of Cyclopentadienes for Cyclopentadienyl Ligands via Cp*Rh-Catalyzed Formal sp C-H Activation/Spiroannulations.

Org Lett 2021 Feb 13;23(3):757-761. Epub 2021 Jan 13.

Department of Material Chemistry, School of Chemistry and Xi'an Key Laboratory of Sustainable Energy Materials Chemistry, Xi'an Jiaotong University, Xi'an 710049, P.R. China.

An efficient Cp*Rh-catalyzed formal C(sp)-H activation/spiroannulation of alkylidene Meldrum's acids with alkynes has been developed using catalytical Cu(OAc) and air as the oxidant. This reaction demonstrates a new and straightforward approach to spirocyclopentadienes with Meldrum's acid moieties in good to excellent yields under mild reaction conditions with a broad substrate scope. Notably, this protocol provides a novel and straightforward approach to cyclopentadienes with various substitution patterns and the corresponding cyclopentadienyl-type ligands from simple substrates.
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http://dx.doi.org/10.1021/acs.orglett.0c03982DOI Listing
February 2021

Clinical Characteristics of 204 Children With Human Adenovirus Type 7 Pneumonia Identified by Whole Genome Sequencing in Liuzhou, China.

Pediatr Infect Dis J 2021 02;40(2):91-95

Department of Pediatrics, University of California San Francisco-Fresno, San Francisco, CA.

Background: Clinical knowledge of human adenovirus type 7 (HAdV-7) pneumonia in children remains limited. Moreover, predictors for disease severity are largely unknown.

Methods: This is a retrospective study of children hospitalized at Liuzhou Maternal and Child Health Hospital, China, with HAdV-7 pneumonia in 2018-2019. Demographics, clinical characteristics, laboratory results, and imaging data were collected. HAdV-7 was identified in plasma using whole genome sequencing, which yielded quantitative HAdV-7 sequence numbers.

Results: There were 204 children; 145 (71%) were <2 years of age. There were 68 children with severe pneumonia (SP) and 136 with nonsevere pneumonia (NSP). Up to 43% in SP group with respiratory failure (SP-RF) were <12 months of age. Median duration of fever before hospitalization was shorter in NSP group than SP groups (P < 0.01). Fourteen (6.9%) underwent mechanical ventilation. There was a significant difference in mean plasma HAdV-7 sequence numbers among SP-RF, SP without respiratory failure (SP-NRF), and NSP groups (2485 ± 165, 2034 ± 124, and 286 ± 35, respectively) (P < 0.01). In a logistic regression analysis, we found that elevated plasma HAdV-7 sequence numbers significantly increased the risk of severe HAdV-7 pneumonia (OR 1.80, 95% confidence interval: 1.59-2.60, P < 0.01) after adjusting for age, fever duration, platelet counts, and serum lactate dehydrogenase levels.

Conclusions: Over two-thirds of children hospitalized with HAdV-7 pneumonia were <2 years of age. Approximately 40% of those with SP associated with respiratory failure were <12 months of age. Those with SP exhibited higher plasma HAdV-7 sequence numbers. Thus, plasma HAdV-7 sequence numbers have a potential in predicting severity of HAdV-7 pneumonia in children.
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http://dx.doi.org/10.1097/INF.0000000000002925DOI Listing
February 2021

Synthesis of molecular metallic barium superhydride: pseudocubic BaH.

Nat Commun 2021 Jan 11;12(1):273. Epub 2021 Jan 11.

State Key Laboratory of Superhard Materials, College of Physics, Jilin University, Changchun, 130012, China.

Following the discovery of high-temperature superconductivity in the La-H system, we studied the formation of new chemical compounds in the barium-hydrogen system at pressures from 75 to 173 GPa. Using in situ generation of hydrogen from NHBH, we synthesized previously unknown superhydride BaH with a pseudocubic (fcc) Ba sublattice in four independent experiments. Density functional theory calculations indicate close agreement between the theoretical and experimental equations of state. In addition, we identified previously known P6/mmm-BaH and possibly BaH and BaH as impurities in the samples. Ab initio calculations show that newly discovered semimetallic BaH contains H and H molecular units and detached H chains which are formed as a result of a Peierls-type distortion of the cubic cage structure. Barium dodecahydride is a unique molecular hydride with metallic conductivity that demonstrates the superconducting transition around 20 K at 140 GPa.
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http://dx.doi.org/10.1038/s41467-020-20103-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801595PMC
January 2021

ASK1/p38‑mediated NLRP3 inflammasome signaling pathway contributes to aberrant retinal angiogenesis in diabetic retinopathy.

Int J Mol Med 2021 02 24;47(2):732-740. Epub 2020 Dec 24.

Department of Ophthalmology, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China.

Diabetic retinopathy (DR) is the leading cause of blindness among the working‑age population in several countries. Despite the available treatments, some patients are diagnosed at the late stages of the disease when treatment is more difficult. Hence, it is crucial that novel targets are identified in order to improve the clinical therapy of DR. In the present study, an animal model of DR and a cell model using primary human retinal microvascular endothelial cells exposed to high glucose were constructed to examine the association between apoptosis signal‑regulating kinase 1 (ASK1)/p38 and NLR family pyrin domain containing 3 (NLRP3) in DR. The results revealed that DR induced inflammatory response and microvascular cell proliferation. NLRP3 contributed to DR‑mediated inflammatory development and progression, which promoted the expression of inflammatory‑related cytokines. In addition, NLRP3 promoted the tube formation of retinal microvascular endothelial cells and angiogenesis. Moreover, further research indicated that the NLRP3‑mediated aberrant retinal angiogenesis in DR was regulated by ASK1 and p38. It was thus suggested that ASK1/p38 may be novel target for the treatment of DR.
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http://dx.doi.org/10.3892/ijmm.2020.4833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797434PMC
February 2021
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