Publications by authors named "Qi Wang"

6,026 Publications

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What lies ahead of us? Collective future thinking in Turkish, Chinese, and American adults.

Mem Cognit 2022 May 20. Epub 2022 May 20.

Culture and Cognition Lab, College of Human Ecology, Cornell University, MVR Hall, Ithaca, NY, 14853-4401, USA.

Collective future thinking, namely the anticipation of events for a group, is a relatively new research area in memory studies. Research to date with predominantly Western populations suggests that people tend to expect negative events for their country's future. In two studies, we investigated the emotional valence and perceived control of anticipated future events of one's country and examined the roles of country identification and national well-being in collective future thinking. US and Chinese college students (Study 1) and US, Chinese, and Turkish adults of a community sample (Study 2) imagined events that could happen to their respective countries in 1 week, 1 year, and 10-15 years. Participants rated each event on emotional valence and perceived control. They also completed measures for their country identification and perceived national well-being. Chinese participants imagined future events for their country to be more positive than did the US and Turkish participants, whereas US participants reported higher perceived control by their country for the future events than did Chinese and Turks. Country identification and national well-being predicted more positive future thinking and also mediated cultural differences in future-event valence and perceived country control. These original findings shed critical light on the characteristics of collective future thinking that are shaped by societal-cultural factors.
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http://dx.doi.org/10.3758/s13421-022-01321-2DOI Listing
May 2022

SNORD15B and SNORA5C: Novel Diagnostic and Prognostic Biomarkers for Colorectal Cancer.

Biomed Res Int 2022 9;2022:8260800. Epub 2022 May 9.

Department of Radiobiology, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, China.

Colorectal cancer (CRC) is presenting a global public health problem with high incidence and mortality. Early diagnosis and treatment are the most important strategies to improve prognosis of this disease. Besides fecal occult blood test (FOBT) and colonoscopy, the most widely used methods for CRC screening currently, more effective methods for early diagnosis or prognostic prediction for CRC are needed. Small nucleolar RNAs (snoRNAs) is a class of noncoding RNAs (ncRNAs) playing crucial roles in carcinogenesis and considered to be promising tumor biomarker. In this study, we found that SNORD15B, SNORD48, and SNORA5C were significantly upregulated in CRC tissues. High levels of SNORD15B, SNORD48, or SNORA5C predicted poor clinical outcomes of CRC patients. Forced expression of SNORD15B or SNORA5C in CRC cells promoted proliferation and colony formation. In a further investigation, association between the level of SNORD15B/SNORA5C and clinicopathological parameters of CRC patient cohorts was analyzed based on data from The Cancer Genome Atlas (TCGA). We found that high expressions of SNORD15B and SNORA5C were significantly associated with age, lymphatic invasion, and history of colon polyps, and they were proved to be independent risk factors for survival of CRC patients. This study confirms that SNORD15B and SNORA5C have oncogenic effects in carcinogenesis of CRC. The findings suggest the two genes as potential diagnostic and prognostic biomarkers for CRC.
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http://dx.doi.org/10.1155/2022/8260800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110153PMC
May 2022

Burden of Coronary Heart Disease and Cancer from Dietary Exposure to Inorganic Arsenic in Adults in China, 2016.

Ann Glob Health 2022 28;88(1):28. Epub 2022 Apr 28.

MOE Key Lab of Environment and Health, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.

Background And Objectives: Inorganic arsenic (iAs) can cause a wide range of health problems, including coronary heart disease (CHD) and lung, bladder, and skin cancer. Although dietary iAs intake is the primary source of iAs, the burden of CHD and cancers from dietary iAs exposure in Chinese adults has not been well known.

Methods: To estimate the iAs exposure level in Chinese adults' diet, we systematically collected food-specific iAs concentrations in China from Chinese and English literature databases during 2000-2020. Food consumption was extracted from two nationwide food and nutrition surveys in China. The population attributable fraction was calculated based on the dose-response relationship between iAs and CHD risk. Combining the 2016 Chinese tumor registry data, we calculated the annual incidence of cancer from dietary iAs exposure to measure the disability-adjusted life year (DALY) in 2016.

Findings: The total amount of daily foodborne iAs intake was 0.55 μg/kg bw/day among Chinese adults. The DALY of foodborne iAs-associated CHD was 3,017,510, which accounted for 10.18% of total CHD DALY in Chinese adults in 2016. Moreover, the carcinogenic DALY for lung cancer, bladder cancer, and skin cancer of Chinese residents in 2016 related to dietary iAs was 314.24, 9.89, and 167.32 thousand, accounting for 2.05%, 1.70%, and 35.5% of the total cancer burden, respectively.

Conclusions: Our findings suggested that dietary iAs exposure causes a substantial disease burden in Chinese adults. More efforts for foodborne iAs control are critical to reducing the disease burden of CHD and cancer in China and other countries with similar dietary patterns.
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http://dx.doi.org/10.5334/aogh.3620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9053568PMC
May 2022

Production of Block Copolymer Poly(3-hydroxybutyrate)--poly(3-hydroxypropionate) with Adjustable Structure from an Inexpensive Carbon Source.

ACS Macro Lett 2013 Nov 22;2(11):996-1000. Epub 2013 Oct 22.

CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Qingdao 266101, China.

The block copolymers poly(3-hydroxybutyrate)--poly(3-hydroxypropionate) (P3HB--P3HP) with a wide range of 3HP fractions from 7.4 mol % to 75 mol % were biosynthesized from inexpensive carbon sources for the first time, differing from previously reported approaches based on sequential addition of precursors. The engineered strain carried two parallel synthetic pathways modulated by independent regulatory systems to produce the 3HB and 3HP monomers, respectively. Manipulating the expression levels of 3HB and 3HP pathways resulted in biosynthesis of block copolymers P3HB--P3HP with varied compositions. Nuclear magnetic resonance and differential scanning calorimetric studies demonstrated novel microstructure and thermal properties not available in related random copolymers and a blend of P3HB and P3HP homopolymers.
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http://dx.doi.org/10.1021/mz400446gDOI Listing
November 2013

MTHFD2 is a potential oncogene for its strong association with poor prognosis and high level of immune infiltrates in urothelial carcinomas of bladder.

BMC Cancer 2022 May 17;22(1):556. Epub 2022 May 17.

Department of Urology, Peking University People's Hospital, 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.

Background: The bifunctional methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase (MTHFD2) has been reported to play an oncogenic role in various types of cancers. However, the function of MTHFD2 in urothelial carcinomas of bladder (UCB) and its association with tumor immune infiltration remains unknown. We aim to examine the suitability of MTHFD2 to be a novel biomarker of bladder cancer and whether MTHFD2 is linked to immune infiltration.

Methods: RNA sequencing data and clinical information (bladder cancer samples: normal samples = 414: 19) were downloaded from The Cancer Genome Atlas official website. Western blot analysis was performed to detect MTHFD2 expression in human bladder cancer (BLCA) cells and normal urothelial cell line SV-HUC-1. Associations between MTHFD2 expression and clinicopathological features were analyzed using Mann Whitney U test or Kruskal-Wallis H test. The "survival" and "survminer" packages were utilized to plot Kaplan-Meier survival curves. Moreover, the gene set enrichment analysis (GSEA) was conducted using a clusterProfiler package. The correlation of MTHFD2 expression with immune infiltration level was estimated using the single sample GSEA (ssGSEA) algorithm. Furthermore, associations between MTHFD2 and immune checkpoint genes were evaluated using the correlation analysis.

Results: Transcriptome analysis manifested that MTHFD2 was highly expressed in UCB tissues than normal bladder tissues, which was further confirmed by western blot analysis in human BLCA cells and SV-HUC-1 cells. Moreover, MTHFD2 high expression was significantly associated with the advanced disease progression. Also, the high expression of MTHFD2 was correlated with poor prognosis, and MTHFD2 was considered as an independent prognostic factor for disease specific survival. Furthermore, a number of cancer-related pathways were enriched in MTHFD2 high group, including NF-κB activation, JAK/STAT, and cancer immunotherapy by PD1 blockade. Several immune checkpoint molecules were also strongly associated with MTHFD2 expression, including PDCD1, CD274, CTLA4, CD276, LAG3, HAVCR2, and TIGIT.

Conclusions: MTHFD2 expression was remarkably elevated in UCB, suggesting that MTHFD2 could be a promising biomarker for BLCA as well as novel target for anti-cancer immunotherapy since its close association with immune infiltration.
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http://dx.doi.org/10.1186/s12885-022-09606-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112551PMC
May 2022

Inert Pepper aptamer-mediated endogenous mRNA recognition and imaging in living cells.

Nucleic Acids Res 2022 May 17. Epub 2022 May 17.

College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers-Ministry of Education, Wuhan University, Luojiashan Street, Wuchang District, Wuhan, HuBei 430072, PR China.

The development of RNA aptamers/fluorophores system is highly desirable for understanding the dynamic molecular biology of RNAs in vivo. Peppers-based imaging systems have been reported and applied for mRNA imaging in living cells. However, the need to insert corresponding RNA aptamer sequences into target RNAs and relatively low fluorescence signal limit its application in endogenous mRNA imaging. Herein, we remolded the original Pepper aptamer and developed a tandem array of inert Pepper (iPepper) fluorescence turn-on system. iPepper allows for efficient and selective imaging of diverse endogenous mRNA species in live cells with minimal agitation of the target mRNAs. We believe iPepper would significantly expand the applications of the aptamer/fluorophore system in endogenous mRNA imaging, and it has the potential to become a powerful tool for real-time studies in living cells and biological processing.
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http://dx.doi.org/10.1093/nar/gkac368DOI Listing
May 2022

RNA modification mapping with JACUSA2.

Genome Biol 2022 May 16;23(1):115. Epub 2022 May 16.

Klaus Tschira Institute for Integrative Computational Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 669, Heidelberg, 69120, Germany.

Several high-throughput antibody-free methods for RNA modification detection from sequencing data have been developed. We present JACUSA2 as a versatile software solution and comprehensive analysis framework for RNA modification detection assays that are based on either the Illumina or Nanopore platform. Importantly, JACUSA2 can integrate information from multiple experiments, such as replicates and different conditions, and different library types, such as first- or second-strand cDNA libraries. We demonstrate its utility, showing analysis workflows for N6-methyladenosine (m6A) and pseudouridine (Ψ) detection on Illumina and Nanopore sequencing data sets. Our software and its R helper package are available as open source solutions.
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http://dx.doi.org/10.1186/s13059-022-02676-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9109409PMC
May 2022

Influence of shrub root combinations and spacing on slope stability: study case at the Yongding River flooding regime, Langfang, China.

Environ Sci Pollut Res Int 2022 May 16. Epub 2022 May 16.

Power China Huadong Engineering Corporation Limited, Hangzhou, 31122, China.

Research on the mechanism of plant root-soil consolidation is a current focus in research into the ecological restoration of banks. The stability of ecological banks is central to this research, and bank stability is closely related to plant combinations and spacing. Recent research on reinforced anchorage of plant roots has mainly focused on root length and angle, and on other parts of the root system, and only a few studies have examined the combination of different types of roots. In this study, a coupled slope stability assessment system is created, composed of root morphological parameters and involving calculations using the finite element model ABACUS. This paper selects the two banks of the lower reaches of the Tiantang River in the flood zone of Yongding River as the research area, and examines slope surface plants. And then the reinforcement effect of different shrub roots combinations and plant spacing are evaluated for determining the optimal shrub layout, with the aim of solving the instability problem of collapsible silty clay bank slopes and associated risks. The results indicated that when the shrub plant spacing is 0.65 m, the optimal shrub combination is Tamarix chinensis + Philadelphus incanus, and when the shrub plant spacing is 0.75 m, the optimal shrub combination is Tamarix chinensis + Euonymus alatus. The study found that the root system morphology and the fibrous roots amount at the foot of the slope can have different degrees of influence on the shallow soil stability of the silty clay slope under different shrubs plant spacing conditions.
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http://dx.doi.org/10.1007/s11356-022-20409-5DOI Listing
May 2022

Novel Insights Into the Sulfated Glucuronic Acid-Based Anti-SARS-CoV-2 Mechanism of Exopolysaccharides From Halophilic Archaeon .

Front Chem 2022 27;10:871509. Epub 2022 Apr 27.

State Key Laboratory of Biochemical Engineering, National Engineering Research Center for Biotechnology (Beijing), Key Laboratory of Biopharmaceutical Production & Formulation Engineering, PLA, Institute of Processing and Engineering, Chinese Academy of Sciences, Beijing, China.

The pandemic caused by SARS-CoV-2 is the most widely spread disease in the 21st century. Due to the continuous emergence of variants across the world, it is necessary to expand our understanding of host-virus interactions and explore new agents against SARS-CoV-2. In this study, it was found exopolysaccharides (EPSs) from halophilic archaeon ATCC33960 can bind to the spike protein of SARS-CoV-2 with the binding constant K of 2.23 nM, block the binding of spike protein to Vero E6 and bronchial epithelial BEAS-2B cells, and inhibit pseudovirus infection. However, EPSs from the gene deletion mutant almost completely lost the antiviral activity against SARS-CoV-2. A significant reduction of glucuronic acid (GlcA) and the sulfation level in EPSs of was clearly observed. Our results indicated that sulfated GlcA in EPSs is possible for a main structural unit in their inhibition of binding of SARS-CoV-2 to host cells, which would provide a novel antiviral mechanism and a guide for designing new agents against SARS-CoV-2.
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http://dx.doi.org/10.3389/fchem.2022.871509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9091367PMC
April 2022

Genome Instability-Associated Long Non-Coding RNAs Reveal Biomarkers for Glioma Immunotherapy and Prognosis.

Front Genet 2022 27;13:850888. Epub 2022 Apr 27.

Department of Neurosurgery, First Affiliated Hospital of Harbin Medical University, Harbin, China.

Genome instability is a hallmark of tumors and is involved in proliferation, invasion, migration, and treatment resistance of many tumors. However, the relationship of genome instability with gliomas remains unclear. Here, we constructed genome instability-derived long non-coding RNA (lncRNA)-based gene signatures (GILncSig) using genome instability-related lncRNAs derived from somatic mutations. Multiple platforms were used to confirm that the GILncSig were closely related to patient prognosis and clinical characteristics. We found that GILncSig, the glioma microenvironment, and glioma cell DNA methylation-based stemness index (mDNAsi) interacted with each other to form a complex regulatory network. In summary, this study confirmed that GILncSig was an independent prognostic indicator for patients, distinguished high-risk and low-risk groups, and affected immune-cell infiltration and tumor-cell stemness indicators (mDNAsi) in the tumor microenvironment, resulting in tumor heterogeneity and immunotherapy resistance. GILncSig are expected to provide new molecular targets for the clinical treatment of patients with gliomas.
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http://dx.doi.org/10.3389/fgene.2022.850888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094631PMC
April 2022

Effects of a Formula with scGOS/lcFOS (9:1) and Glycomacropeptide (GMP) Supplementation on the Gut Microbiota of Very Preterm Infants.

Nutrients 2022 May 1;14(9). Epub 2022 May 1.

Department of Pediatrics, Peking University Third Hospital, Beijing 100191, China.

Microbial colonization of very preterm (VPT) infants is detrimentally affected by the complex interplay of physiological, dietary, medical, and environmental factors. The aim of this study was to evaluate the effects of an infant formula containing the specific prebiotic mixture of scGOS/lcFOS (9:1) and glycomacropeptide (GMP) on the composition and function of VPT infants' gut microbiota. Metagenomic analysis was performed on the gut microbiota of VPT infants sampled at four time points: 24 h before the trial and 7, 14, and 28 days after the trial. Functional profiling was aggregated into gut and brain modules (GBMs) and gut metabolic modules (GMMs) based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. , , and were dominant species in both the test group and the control group. After the 4-week intervention, the abundance of in the test group was significantly increased. We found two GBMs (quinolinic acid synthesis and kynurenine degradation) and four GMMs (glutamine degradation, glyoxylate bypass, dissimilatory nitrate reduction, and preparatory phase of glycolysis) were significantly enriched in the test group, respectively. The results of this study suggested that formula enriched with scGOS/lcFOS (9:1) and GPM is beneficial to the intestinal microecology of VPT infants.
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http://dx.doi.org/10.3390/nu14091901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102166PMC
May 2022

Factors Driving Microbial Community Dynamics and Potential Health Effects of Bacterial Pathogen on Landscape Lakes with Reclaimed Water Replenishment in Beijing, PR China.

Int J Environ Res Public Health 2022 Apr 22;19(9). Epub 2022 Apr 22.

Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Assessing the bacteria pathogens in the lakes with reclaimed water as major influents are important for public health. This study investigated microbial communities of five landscape lakes replenished by reclaimed water, then analyzed driven factors and identified health effects of bacterial pathogens. 16S rRNA gene sequence analysis demonstrated that , , , and were the most dominant phyla in five landscape lakes. The microbial community diversities were higher in June and July than that in other months. Temperature, total nitrogen and phosphorus were the main drivers of the dominant microbial from the Redundancy analysis (RDA) results. Various potential bacterial pathogens were identified, including , , , , and , etc, some of which are easily infectious to human. The microbial network analysis showed that some potential pathogens were nodes that had significant health effects. The work provides a basis for understanding the microbial community dynamics and safety issues for health effects in landscape lakes replenished by reclaimed water.
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http://dx.doi.org/10.3390/ijerph19095127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106022PMC
April 2022

Hepatoprotective Effects of Albumin-Encapsulated Nanoparticles of a Curcumin Derivative COP-22 against Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Injury in Mice.

Int J Mol Sci 2022 Apr 28;23(9). Epub 2022 Apr 28.

School of Pharmaceutical Sciences, Liaocheng University, 1 Hunan Street, Liaocheng 252059, China.

Acute liver injury (ALI) is a severe syndrome and can further develop into acute liver failure (ALF) which can lead to high mortality and cause irreversible liver injuries in the clinic. Liver transplantation is the most common treatment; however, liver donors are lacking, and the progression of ALF is rapid. Nanoparticles can increase the bioavailability and the targeted accumulation of drugs in the liver, so as to significantly improve the therapeutic effect of ALI. Curcumin derivative COP-22 exhibits low cytotoxicity and effective anti-inflammatory activity; however, it has poor water solubility. In this study, COP-22-loaded bovine serum albumin (BSA) nanoparticles (22 NPs) were prepared and characterized. They exhibit effective hepatoprotective effects by inhibiting inflammation, oxidative stress, and apoptosis on Lipopolysaccharide/D-Galactosamine-induced acute liver injury of mice. The anti-inflammatory activity of 22 NPs is related to the regulation of the NF-κB signaling pathways; the antioxidant activity is related to the regulation of the Nrf2 signaling pathways; and the apoptosis activity is related to mitochondrial pathways, involving Bcl-2 family and Caspase-3 protein. These three cellular pathways are interrelated and affected each other. Moreover, 22 NPs could be passively targeted to accumulate in the liver through the retention effect and are more easily absorbed than 22.HCl salt in the liver.
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http://dx.doi.org/10.3390/ijms23094903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9102161PMC
April 2022

Fecal Microbiota Transplantation Derived from Alzheimer's Disease Mice Worsens Brain Trauma Outcomes in Wild-Type Controls.

Int J Mol Sci 2022 Apr 19;23(9). Epub 2022 Apr 19.

Department of Neurosurgery and Center for Neuroregeneration, Houston Methodist Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA.

Traumatic brain injury (TBI) causes neuroinflammation and neurodegeneration, both of which increase the risk and accelerate the progression of Alzheimer's disease (AD). The gut microbiome is an essential modulator of the immune system, impacting the brain. AD has been related with reduced diversity and alterations in the community composition of the gut microbiota. This study aimed to determine whether the gut microbiota from AD mice exacerbates neurological deficits after TBI in control mice. We prepared fecal microbiota transplants from 18 to 24 month old 3×Tg-AD (FMT-AD) and from healthy control (FMT-young) mice. FMTs were administered orally to young control C57BL/6 (wild-type, WT) mice after they underwent controlled cortical impact (CCI) injury, as a model of TBI. Then, we characterized the microbiota composition of the fecal samples by full-length 16S rRNA gene sequencing analysis. We collected the blood, brain, and gut tissues for protein and immunohistochemical analysis. Our results showed that FMT-AD administration stimulates a higher relative abundance of the genus and a decrease in compared to FMT-young in WT mice. Furthermore, WT mice exhibited larger lesion, increased activated microglia/macrophages, and reduced motor recovery after FMT-AD compared to FMT-young one day after TBI. In summary, we observed gut microbiota from AD mice to have a detrimental effect and aggravate the neuroinflammatory response and neurological outcomes after TBI in young WT mice.
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http://dx.doi.org/10.3390/ijms23094476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9103830PMC
April 2022

Telocytes in the esophageal wall of chickens: a tale of subepithelial telocytes.

Poult Sci 2022 Mar 15;101(7):101859. Epub 2022 Mar 15.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Jiangsu Province, 210095, China. Electronic address:

The esophagus is a tubular organ which act as a passage for food from oral cavity to stomach. Telocytes (TCs) are a unique type of interstitial cell whose existence in many organs of various species still remains unknown. In the present study, we used transmission electron microscopy (TEM) and immunohistochemistry (CD34, Vimentin, PDGFR-α) to identify subepithelial TCs in the esophageal wall of chickens. TEM micrographs confirmed the presence of TCs in the lamina propria, tunica submucosa, and tunica muscularis muscular layer of the esophageal wall. A large population of TCs were observed just beneath the epithelial layer of the esophageal wall, and the TCs demonstrated structural heterogenicity, featuring various cell body shapes of cell bodies and telopodes (Tps) with podoms, podomeres, and dichotomous branching. Furthermore, a large number of extracellular vesicles were found to be associated with TCs/Tps. Cellular extensions from TCs were observed in close proximity to blood vessels, immune cells, and mucosal glands. In the submucosa, Tps and immune cells were in very close contact. Immunohistochemical results showed that there were CD34+ cells, vimentin+ cells, and PDGFR-α+ cells in the subepithelium, lamina propria, and mucosal glands of the chicken esophageal wall, which was consistent with the TEM results. Overall, our data confirmed the existence of TCs in the chicken esophagus and suggested that TCs might contribute to epithelial regeneration and tissue homeostasis.
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http://dx.doi.org/10.1016/j.psj.2022.101859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108747PMC
March 2022

Endohedral σ-Diradical Nitrogen-Vacancy Diamond Nanoclusters with a Confined Magnetic Space and Strong Electronic Spin Couplings.

J Phys Chem A 2022 May 13. Epub 2022 May 13.

School of Chemistry and Chemical Engineering, Shandong University, Jinan, 250100, People's Republic of China.

The electronic properties and their modulations for the nitrogen-vacancy (NV) centers in various nanoscale diamonds are of profound current interest because of their potential applications. However, although the NV centers as chromophores in diamond are the most widely studied, surprisingly, little is known about their magnetic spin coupling properties up to now. Here, we for the first time show, using the spin-polarized DFT calculations, that the NV centers can act as unique endohedral σ-diradical magnets in diamond nanoclusters and exhibit quite strong ferromagnetic (FM) or antiferromagnetic (AFM) spin coupling characteristics due to their unique endotetrahedral structures with favorable radical-radical contacts. Although the neutral NV center (NV) in its doublet ground state exhibits quite strong AFM spin coupling among three radical C-sites (i.e., an AFM triradical center), interestingly, excess electron injection can convert it to a FM diradical magnet (i.e., the triplet ground state NV) with almost unchanged -coupling magnitude, and the -coupling of the nanocluster can be noticeably enhanced by F-termination of the surface due to triradical spin delocalization mediated by excess electron. However, interior modification (one C in the endotetrahedron core is substituted by N or B or is hydrogenated) can assign the nanocluster perfect AFM diradical character. The spin coupling strength presents a quasilinear correlation with the distance between the two C radicals in the NV core for the same size of the clusters and a high linear correlation with the energy difference between two singly occupied molecular orbitals. Clearly, the FM and AFM couplings as well as their switching behavior in such NV defect diamond nanoclusters featuring the endohedral σ-diradicals are a novel type of promising magnetic material motifs. These findings open up promising spintronic application prospects of the NV diamonds and provide helpful information for the design of inorganic magnetic materials and logic devices.
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http://dx.doi.org/10.1021/acs.jpca.2c01709DOI Listing
May 2022

Hyperoside: A review on its sources, biological activities, and molecular mechanisms.

Phytother Res 2022 May 13. Epub 2022 May 13.

College of Pharmacy, Shandong University of Traditional Chinese Medicine, Ji'nan, China.

Hyperoside is a natural flavonol glycoside in various plants, such as Crataegus pinnatifida Bge, Forsythia suspensa, and Cuscuta chinensis Lam. Medical research has found that hyperoside possesses a broad spectrum of biological activities, including anticancer, anti-inflammatory, antibacterial, antiviral, antidepressant, and organ protective effects. These pharmacological properties lay the foundation for its use in treating multiple diseases, such as sepsis, arthritis, colitis, diabetic nephropathy, myocardial ischemia-reperfusion, pulmonary fibrosis, and cancers. Hyperoside is obtained from the plants and chemical synthesis. This study aims to provide a comprehensive overview of hyperoside on its sources and biological activities to provide insights into its therapeutic potential, and to provide a basis for high-quality studies to determine the clinical efficacy of this compound.
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http://dx.doi.org/10.1002/ptr.7478DOI Listing
May 2022

Hua-Tan-Sheng-Jing Decoction Treats Obesity With Oligoasthenozoospermia by Up-Regulating the PI3K-AKT and Down-Regulating the JNK MAPK Signaling Pathways: At the Crossroad of Obesity and Oligoasthenozoospermia.

Front Pharmacol 2022 26;13:896434. Epub 2022 Apr 26.

National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China.

Oligoasthenozoospermia is the leading cause of male infertility, seriously affecting men's health and increasing the societal medical burden. In recent years, obesity-related oligoasthenozoospermia has attracted increased attention from researchers to find a cure. This study aimed to evaluate the efficacy of Hua-Tan-Sheng-Jing decoction (HTSJD) in treating obesity with oligoasthenozoospermia, determine its active ingredients and identify its mechanism of action. The ingredients of HTSJD were determined by combining the ultra-performance liquid chromatography with mass spectrometry (UPLC-MS/MS) and systems pharmacology approach. The common pathogenesis of obesity and oligoasthenozoospermia and the potential mechanism of HTSJD against obesity with oligoasthenozoospermia were obtained through target fishing, network construction, and enrichment analyses. Further, molecular docking of the key ingredients with the upstream receptors of the key signaling pathways of the potential mechanism was used to predict their affinity. Finally, high-fat-induced obesity with oligoasthenozoospermia rat model was constructed to determine the effects of HTSJD on semen concentration, sperm motility, body weight, and serum lipid metabolism. The key proteins were validated by immunohistochemistry (IHC). A total of 70 effective components and 847 potential targets of HTSJD (H targets) were identified, of which 743 were common targets related to obesity and oligoasthenozoospermia (O-O targets) mainly enriched in the pathways related to inflammation, oxidative stress and hormone regulation. Finally, 143 common targets (H-O-O targets) for HTSJD against obesity with oligoasthenozoospermia were obtained. Combining the hub genes and the results of Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of H-O-O targets, PI3K-AKT and MAPK signaling pathways were identified as the key pathways. Molecular docking results showed that Diosgenin, Kaempferol, Quercetin, Hederagenin, Isorhamnetin may act on the related pathways by docking EGFR, IGF1R and INSR. The animal-based experiments confirmed that HTSJD improves the sperm quality of high-fat diet-fed rats by reducing their body weight and blood lipid levels, influencing the PI3K-AKT and MAPK signaling pathways and altering the corresponding protein expressions. HTSJD treats obesity with oligoasthenozoospermia by up-regulating the PI3K-AKT signaling pathway and down-regulating the MAPK signaling pathway, which are at the crossroad of obesity and oligoasthenozoospermia.
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http://dx.doi.org/10.3389/fphar.2022.896434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086321PMC
April 2022

The Interaction of Influenza A NS1 and Cellular TRBP Protein Modulates the Function of RNA Interference Machinery.

Front Microbiol 2022 26;13:859420. Epub 2022 Apr 26.

CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Influenza A virus (IAV), one of the most prevalent respiratory diseases, causes pandemics around the world. The multifunctional non-structural protein 1 (NS1) of IAV is a viral antagonist that suppresses host antiviral response. However, the mechanism by which NS1 modulates the RNA interference (RNAi) pathway remains unclear. Here, we identified interactions between NS1 proteins of Influenza A/PR8/34 (H1N1; IAV-PR8) and Influenza A/WSN/1/33 (H1N1; IAV-WSN) and Dicer's cofactor TAR-RNA binding protein (TRBP). We found that the N-terminal RNA binding domain (RBD) of NS1 and the first two domains of TRBP protein mediated this interaction. Furthermore, two amino acid residues (Arg at position 38 and Lys at position 41) in NS1 were essential for the interaction. We generated TRBP knockout cells and found that NS1 instead of NS1 mutants (two-point mutations within NS1, R38A/K41A) inhibited the process of microRNA (miRNA) maturation by binding with TRBP. PR8-infected cells showed masking of short hairpin RNA (shRNA)-mediated RNAi, which was not observed after mutant virus-containing NS1 mutation (R38A/K41A, termed PR8/3841) infection. Moreover, abundant viral small interfering RNAs (vsiRNAs) were detected and upon PR8/3841 infection. We identify, for the first time, the interaction between NS1 and TRBP that affects host RNAi machinery.
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http://dx.doi.org/10.3389/fmicb.2022.859420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9087287PMC
April 2022

Identification of potential prognostic biomarkers for hepatocellular carcinoma.

J Gastrointest Oncol 2022 Apr;13(2):812-821

Department of Orthopedics, Tianjin Nankai Hospital, Tianjin, China.

Background: The incidence of liver cancer is increasing every year. Hepatocellular carcinoma (HCC) accounts for nearly 90% of liver cancer, and the overall 5-year survival rate of become of Hepatocellular carcinoma patients less than 20%. However, the molecular mechanism of HCC progression and prognosis still requires further exploration.

Methods: In this study, we downloaded the gene expression data from the Cancer Genome Atlas (TCGA) Genomic Data and the official website of GEO database. Weighted gene co-expression network analysis (WGCNA) and Pearson's correlation coefficient were utilized to detect the gene modules. The shared differentially-expressed genes (DEGs) were screened out by a Venn diagram, and the hub genes were identified through protein-protein interaction (PPI) network analyses. GO and KEGG enrichment analyses were constructed for these hub genes. Overall survival (OS) and correlation analysis were conducted to investigate the relationship between the hub genes and clinical features.

Results: We screened out 27 shared DEGs, and the mainly enriched GO terms were mitotic nuclear division, chromosomal region, and tubulin binding. Furthermore, the top three enriched KEGG pathways were "cell cycle", "oocyte meiosis", and "p53 signaling pathway". According to the Maximal Clique Centrality (MCC) algorithm, the top 10 candidate hub genes were , , , , , , , , , and , among which BIRC5, CDC20, and UBE2C showed a strong correlation with the OS.

Conclusions: Three hub genes (, , and ) were identified and found to be correlated to the progression and prognosis of HCC. These may become potential targets for HCC therapy.
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http://dx.doi.org/10.21037/jgo-22-303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9086056PMC
April 2022

Antimicrobial Mechanisms of Enterocin CHQS Against Candida albicans.

Curr Microbiol 2022 May 13;79(7):191. Epub 2022 May 13.

School of Chemical Engineering and Technology, Tianjin University, Tianjin, 300350, China.

Candida albicans is the most common fungal pathogen in hospital-acquired infections, which is extremely harmful to health. The increasing fungal infections is requiring the rapid development of novel antifungal agents. In this study, the antimicrobial activity of CHQS, an enterocin isolated from Enterococcus faecalis TG2 against C. albicans was confirmed by the minimum inhibitory concentration, minimum fungicidal concentration, and time-kill curve. Aniline blue and calcofluor white staining methods showed that CHQS remarkably affected β-1,3-glucan and chitin cell wall components and made cell wall more vulnerable. The C. albicans cell wall rupture and intracellular vacuolation were observed by TEM and SEM. Moreover, CHQS induced the accumulation of intracellular reactive oxygen species and decreased mitochondrial membrane potential. These results suggested that CHQS might have a complex multi-target antimicrobial mechanism against C. albicans. In addition, the use of CHQS combined with amphotericin B showed synergistic antimicrobial effects against C. albicans. In conclusion, enterocin CHQS, a natural product with antimicrobial effect, might has a bright future for the development of new antifungal drugs.
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http://dx.doi.org/10.1007/s00284-022-02878-6DOI Listing
May 2022

Rapid quantitative analysis and suspect screening of per-and polyfluorinated alkyl substances (PFASs) in aqueous film-forming foams (AFFFs) and municipal wastewater samples by Nano-ESI-HRMS.

Water Res 2022 May 3;219:118542. Epub 2022 May 3.

Department of Chemistry and Environmental Science, New Jersey Institute of Technology, Newark, NJ, United States. Electronic address:

A rapid analytical method for per- and polyfluoroalkyl substances (PFASs) combining nano-electrospray ionization and high-resolution mass spectrometry (Nano-ESI-HRMS) was developed and applied to aqueous film-forming foams (AFFFs) and wastewater samples collected from three local wastewater treatment plants (WWTPs). This method exhibited high sensitivity with lower limits of detection (LODs) of 3.2∼36.2 ng/L for 22 target PFAS analytes. In AFFF formulations, Nano-ESI-HRMS enabled the first-time detection of trifluoromethanesulfonic acid (TFMS), perfluoroethyl cyclohexanesulfonate (PFECHS), 6:2 fluorotelomer sulfonyl amido sulfonic acid (6:2 FTSAS-SO), N-ammoniopropyl perfluoroalkanesulfonamidopropylsulfonate (N-AmP-FASAPS, n = 3-6), ketone-perfluorooctanesulfonic acid (Keto-PFOS), fluorotelomer unsaturated amide sulfonic acid (FTUAmS, n = 7), and 6:2 fluorotelomer amide (6:2 FTAm). Their structures were verified by the tandem MS analysis using collision-induced dissociation. Further, the combination of absolute and semi-quantification results revealed 16 PFASs from 9 PFAS classes as dominant AFFF constituents, accounting for 88.2∼96.5% of the total detected anionic and zwitterionic PFASs, including perfluorinated sulfonic acids (PFSAs, n = 1,4∼8), 6:2 fluorotelomer sulfonates (6:2 FTS), fluorotelomer thioether amido sulfonic acid (FTSAS, n = 6,8), fluorotelomer sulfinyl amido sulfonic acid (FTSAS-SO, n = 6,8), N-AmP-FASAPS (n = 6), 6:2 fluorotelomer sulfonamide alkylbetaine (6:2 FTAB), perfluoroalkylsulfonamido amino carboxylate (PFASAC, n = 6), 2-((perfluorooctyl)thio)acetatic acid (Thio-8:2 FTCA), and 6:2 FTAm. At WWTPs, aerobic and anaerobic biotransformation of PFAS precursors at the aeration tanks and secondary clarifiers were evident by the generation of mid/short-chain perfluoroalkyl acids, such as perfluoroheptanoic acid (PFHpA), perfluorohexanoic acid (PFHxA), perfluoropentanoic acid (PFPeA), as well as the emergence of ultrashort trifluoroacetic acid (TFA) and TFMS and several novel fluorotelomer carboxylic acids (FTCAs). Overall, Nano-ESI-HRMS enabled comprehensive PFAS quantitative analysis and suspect screening, applicable for rapid investigation and assessment of PFAS-related exposure and treatment in environmental matrixes. Our results also revealed that AFFFs and municipal wastewaters are two key sources contributing to the prevalent detection of ultrashort-chain PFASs (e.g., TFMS and TFA) in water.
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http://dx.doi.org/10.1016/j.watres.2022.118542DOI Listing
May 2022

Developing dietary curcumin mono-carbonyl piperidinone analogs as Nrf2-dependent cytoprotectors against oxidative damage: Structure-activity relationship and mechanisms.

Free Radic Biol Med 2022 May 10;186:66-75. Epub 2022 May 10.

State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou, Gansu, 730000, China. Electronic address:

Developing nuclear factor erythroid-2 related factor 2 (Nrf2)-dependent cytoprotectors against oxidative damage is of concern because they can effectively reduce the risk of oxidative stress-related diseases, such as cancer and inflammation. This work was aimed to develop more active Nrf2-dependent cytoprotectors than curcumin, a well-known dietary Nrf2 activator and cancer chemopreventive agent. Herein we designed a panel of curcumin-inspired mono-carbonyl piperidinone analogs differentiated by placing distinct electron-withdrawing and electron-donating groups on its two aromatic rings in the ortho, meta, or para position to the linker of α, β-unsaturated piperidinone. Among these, the ortho-fluorine-substituted CN-2F surfaced as a promising lead molecule, which was significantly superior to the parent curcumin in protecting HepG2 cells from oxidative damage induced by tert-butyl hydroperoxide. Mechanically, by virtue of its Michael receptor units and ortho-substituted mode, CN-2F activated Nrf2 signaling by covalently modifying Cys-151 and Cys-288 residues at Keap1, promoting phosphorylation of JNK, ERK and p38, as well as inhibiting Nrf2 degradation. This work reveals the structural determinants and the activity mechanisms of CN-2F as an Nrf2-dependent cytoprotector, and gives useful information on how to design curcumin-inspired Nrf2 activators and cytoprotectors.
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http://dx.doi.org/10.1016/j.freeradbiomed.2022.05.009DOI Listing
May 2022

Interactions of two phosphate ester monomers with hydroxyapatite and collagen fibers and their contributions to dentine bond performance.

J Dent 2022 May 10;122:104159. Epub 2022 May 10.

Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, Jiangsu Province Key Laboratory of Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing 210029, China. Electronic address:

Objectives: To evaluate the interactions of two phosphate ester monomers [10-methacryloyloxydecyl dihydrogen phosphate (10-MDP) and dipentaerythritol penta-acrylate phosphate (PENTA)] with hydroxyapatite and collagen and understand their influence on dentine bonding.

Methods: Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, X-ray diffraction, nuclear magnetic resonance, ultraviolet-visible, and molecular docking were applied for separately evaluating the interactions of two monomers with hydroxyapatite and collagen. Hydrophilicity tests and morphological observation were employed to characterize pretreated dentine. Microtensile bond strength (μTBS) and nanoleakage were investigated to evaluate the bonding performance. Hydroxyproline assay, in situ zymography, and matrix metalloproteinase-9 (MMP-9) activity assay were used to confirm the MMP inhibition.

Results: Chemoanalytic characterization confirmed the interactions of 10-MDP and PENTA with hydroxyapatite and collagen. The interactions of PENTA were weaker than 10-MDP. PENTA possessed better dentine tubule sealing after etching than 10-MDP. Dentine treated with PENTA was more hydrophilic than 10-MDP. 10-MDP and PENTA treating significantly increased the initial μTBS than the control group without primer conditioning. μTBS decreased significantly during aging, and the decrease was more severe in the PENTA group than 10-MDP. The 10-MDP and PENTA groups exhibited relatively less fluorescence than the control. The relative inhibition percentages of MMP-9 decreased in the order of 10-MDP-Ca salt, 10-MDP and PENTA. The 10-MDP, PENTA, and 10-MDP-Ca salt groups showed significantly lower hydroxyproline contents than the control.

Conclusions: Although PENTA adsorbed on hydroxyapatite, it did not form a stable calcium salt. The interactions of 10-MDP with hydroxyapatite and collagen are different than those of PENTA.

Clinical Significance: The sealing of dentinal tubules by PENTA and the inhibition of MMP by 10-MDP and its calcium salts contribute to improving the dentine bonding durability.
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http://dx.doi.org/10.1016/j.jdent.2022.104159DOI Listing
May 2022

Dermal Microvascular Units in Domestic Pigs (): Role as Transdermal Passive Immune Channels.

Front Vet Sci 2022 25;9:891286. Epub 2022 Apr 25.

MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.

The dermal microvascular unit (DMU) is a perivascular functional unit in the dermis. It is composed of microvascular and capillary lymphatics surrounded by immune cells. In this study, jet needle-free injection system was used to injected biocompatible carbon nanoparticles into the cervical skin of domestic pigs () and assessed the morphological distribution of DMUs by hematoxylin erythrosine staining, immunohistochemistry (IHC), and transmission electron microscopy (TEM), and TEM was also used to observe the ultrastructural changes of DMUs after jet needle-free injection. Following our study, we identified DMUs in the dermis stratum papillare and similar structures in the dermis stratum reticulare, but the aggregation of CD68 and CD1a cells in the dermis stratum papillare of DMUs by IHC confirmed that DMUs act as reservoirs of dermal immune cells, while similar structures in the dermis stratum reticulare should not be considered as DMUs. Ultrastructure of DMUs was revealed by TEM. Marvelous changes were found following xenobiotics attack, including the rearrangement of endothelial cells and pericytes, and the reactivity of immune cells. Novel interstitial cell telocyte (TC) was also identified around the microvasculature, which may have been previously known as the veil cell. Our results successfully identified the distribution of DMUs in the skin of domestic pigs, which might act as reservoirs of immune cells in the skin and play a role in immune surveillance and immune defense.
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http://dx.doi.org/10.3389/fvets.2022.891286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083201PMC
April 2022

Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development.

Burns Trauma 2022 9;10:tkac013. Epub 2022 May 9.

Department of Dermatology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.

Background: A keloid is a disease of excessive fibrosis that is characterized by the aberrant proliferation of fibroblasts. However, the molecular mechanisms of fibroblasts during the development of keloids remain unclear. This study aims to identify new molecular targets that promote the proliferation and migration of keloid fibroblasts, providing new ideas for the prevention and treatment of keloids.

Methods: We utilized bioinformatics tools to analyze data from keloid fibroblasts (KFs) available in the Gene Expression Omnibus (GEO) database to identify the key genes involved in keloid development. Homeobox C6 () emerged as a hub gene in KFs from the GEO database was verified in keloid tissue samples and KFs using reverse transcription-quantitative polymerase chain reaction, western blot (WB) and immunohistochemistry. Subsequently, the effects of downregulated expression on the cellular behaviors of KFs were examined by performing Cell Counting Kit-8, flow cytometry, transwell migration and WB assays. Meanwhile, we performed transcriptome sequencing and gene set enrichment analysis (GSEA) to further explore HOXC6-related mechanisms and validated the signaling pathways by performing a series of experiments.

Results: was the top-ranking hub gene of KFs in microarray datasets from GEO and was upregulated in keloid tissue samples and KFs. Downregulation of inhibited proliferation, migration and extracellular matrix (ECM) accumulation and promoted KF apoptosis. GSEA predicted that the hypoxia signaling pathway was associated with in KFs. Transcriptome sequencing suggested that the extracellular regulated protein kinase (ERK) pathway was one of the downstream pathways of in KFs. Our experiments confirmed that hypoxia-inducible factor-1α (HIF-1α) upregulates , contributing to KFs proliferation, migration, apoptosis inhibition and collagen accumulation through the ERK signaling pathway.

Conclusions: Our findings first revealed that acts as an oncogenic driver in the molecular mechanisms of fibroblasts in keloids. The HIF-1α/HOXC6/ERK axis promotes proliferation, migration and ECM production by KFs, contributing to the progression of keloids. Taken together, HOXC6 may serve as a promising novel therapeutic target and new focus for research designed to understand the pathogenesis of keloids.
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http://dx.doi.org/10.1093/burnst/tkac013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9085412PMC
May 2022

mRNA microarray analysis for the identification of potential biomarkers for vital reaction in burned skin: a preliminary pilot study.

Forensic Sci Med Pathol 2022 May 11. Epub 2022 May 11.

Department of Forensic Pathology, School of Forensic Medicine, Southern Medical University, No. 1023, South Shatai Road, Guangzhou, 510515, China.

The identification of ante- and post-mortem burns is challenging in forensic pathology. In this study, microarray analysis was used to detect the mRNA expression profiles in the skin of an experimental burn mouse model; the results were validated using RT-qPCR. Differentially expressed mRNAs (DE-mRNAs) were assessed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Our results revealed that mRNA expression of 501 genes was significantly different, of which 273 were upregulated and 228 were downregulated in ante-mortem burned mice skin. The expression levels of eight random mRNAs were consistent when measured using the microarray assay-based method and RT-qPCR. Genes from different functional categories and signalling pathways were enriched, including interleukin-20 binding, type IV hypersensitivity, negative regulation of acute inflammatory response, sensory organ development, endocytosis, neuroactive ligand-receptor interaction, and Jak-STAT signalling pathway. Only five of the eight mRNAs exhibited consistent changes in expression between burned skin samples of mice and human autopsy specimens. Our findings showed that DE-mRNAs revealed using microarray are potential biomarkers of ante-mortem burns. However, DE-mRNAs identified from experimental animal models cannot be directly extended to autopsy specimens without careful validation.
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http://dx.doi.org/10.1007/s12024-022-00474-5DOI Listing
May 2022

Water-soluble bright NIR AIEgens with hybrid ROS for wash-free mitochondrial "off-on" imaging and photodynamic therapy.

Chem Commun (Camb) 2022 May 11. Epub 2022 May 11.

Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China.

Several aggregation-induced emission luminogens (AIEgens) with excellent water-solubility and near-infrared emission were designed and synthesized for wash-free "off-on" mitochondrial imaging and photodynamic therapy of HeLa cells. The AIEgen TEPP exhibits both bright near-infrared emission ( = 17.8%) and high hybrid ROS productivity (including OH˙ and O).
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http://dx.doi.org/10.1039/d2cc01559eDOI Listing
May 2022

Caffeine Ameliorates AKT-Driven Nonalcoholic Steatohepatitis by Suppressing Lipogenesis and MyD88 Palmitoylation.

J Agric Food Chem 2022 May 10. Epub 2022 May 10.

College of Pharmacy, Hubei University of Chinese Medicine, Wuhan 430065, People's Republic of China.

Dysregulated hepatic lipogenesis represents a promising druggable target for treating nonalcoholic steatohepatitis (NASH). This work aims to evaluate the therapeutic efficacy of caffeine in a NASH mouse model displaying increased hepatic lipogenesis driven by constitutive hepatic overexpression of the active v-akt murine thymoma viral oncogene homolog (AKT). Caffeine was administered in the AKT mice to study the efficacy . AKT-transfected and insulin-stimulated human hepatoma cells were used for experiments. The results demonstrated that caffeine ameliorated hepatic steatosis and inflammatory injury . Mechanistically, caffeine repressed the AKT/mTORC1 and SREBP-1/ACC/FASN signaling in mice and . Furthermore, caffeine impaired NF-κB activation by stabilizing IκBα, resulting in a reduction of proinflammatory mediators interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α). Notably, caffeine abolished mTORC1/FASN-dependent MyD88 palmitoylation, which could be essential for its anti-inflammatory potential. Collectively, these results suggest that caffeine consumption could be advantageous in the prevention and therapy of NASH, especially in the subset accompanied by increased lipogenesis.
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http://dx.doi.org/10.1021/acs.jafc.2c01013DOI Listing
May 2022

TROP2 as Patient-Tailoring but Not Prognostic Biomarker for Breast Cancer.

Onco Targets Ther 2022 3;15:509-520. Epub 2022 May 3.

Biotherapeutics Discovery Research Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, People's Republic of China.

Purpose: Trophoblast cell surface antigen 2 (TROP2) has emerged as a promising target of antibody-drug conjugates (ADCs) for triple-negative breast cancer (TNBC), as well as other breast cancers (BCs). This study aims to investigate the biomarker value of TROP2 for patient-tailoring and prognostic for BC patients, including TNBC.

Methods: The levels of TROP2 expression in 404 Chinese BC tissues on tissue microarrays (TMAs) were quantified by immunohistochemistry and their correlations to the clinicopathological factors and the overall survival rate were analyzed. Also, BC cell lines and patient-derived organoids (PDOs) with different TROP2 expression levels were employed to investigate the correlation between TROP2 expression levels and the therapeutic responses to DS001, a TROP2-directed ADC molecule with stable linker and potent payload.

Results: TROP2 overexpression was identified in significantly more ( = 0.046) tumor tissues (41.08%, 99/241) than normal adjacent tissues (31.29%, 51/163) from Chinese BC patients, and in significantly more ( = 0.024) TNBC patients (59.38%, 19/32) than in other BC types (38.28%, 80/209). BC cell line with the lowest TROP2 expression level failed to respond to DS001 treatment. The levels of TROP2 expression were determined to be significantly correlated with the potencies of DS001 treatment, but not with the overall survival rates of the patients.

Conclusion: Our results demonstrated that TROP2 could serve as a patient-tailoring and predictive biomarker for ADC therapeutics but not as a general prognostic biomarker to predicate patient survival.
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http://dx.doi.org/10.2147/OTT.S354048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9078428PMC
May 2022
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