Publications by authors named "W Huang"

20,355 Publications

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Research progress and application opportunities of nanoparticle-protein corona complexes.

Biomed Pharmacother 2021 Apr 10;139:111541. Epub 2021 Apr 10.

Department of immunology, School of Basic Medical Sciences and School of Pharmacy, Nanchang University, Nanchang 330006, China.

Nanoparticles (NPs) can be used to design for nanomedicines with different chemical surface properties owing to their size advantages and the capacity of specific delivery to targeted sites in organisms. The discovery of the presence of protein corona (PC) has changed our classical view of NPs, stimulating researchers to investigate the in vivo fate of NPs as they enter biological systems. Both NPs and PC have their specificity but complement each other, so they should be considered as a whole. The formation and characterization of NP-PC complexes provide new insights into the design, functionalization, and application of nanocarriers. Based on progress of recent researches, we reviewed the formation, characterization, and composition of the PC, and introduced those critical factors influencing PC, simultaneously expound the effect of PC on the biological function of NPs. Especially we put forward the opportunities and challenges when NP-PC as a novel nano-drug carrier for targeted applications. Furthermore, we discussed the pros versus cons of the PC, as well as how to make better PC in the future application of NPs.
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http://dx.doi.org/10.1016/j.biopha.2021.111541DOI Listing
April 2021

Pathogenesis of acephalic spermatozoa syndrome caused by SUN5 Variant.

Mol Hum Reprod 2021 Apr 12. Epub 2021 Apr 12.

Laboratory of Basic Medicine, Dongfang Hospital (900th Hospital of the Joint Logistics Team), Xiamen University, Fuzhou, 350025, China.

Acephalic spermatozoa syndrome (ASS) is a rare teratozoospermia that leads to male infertility. Previous work suggested a genetic origin. Variants of Sad1 and UNC84 domain containing 5 (SUN5) are the main genetic cause of ASS, however its pathogenesis remains unclear. Here, we performed whole-exome sequencing in ten unrelated ASS and identified two homozygous variants, c.381delA[p.V128Sfs7*] and c.675C>A[p.Y225X], and one compound variant, c.88 C > T[p.R30X] and c.381 delA [p.V128Sfs7*], in SUN5 in four patients. The c.381delA variant had been identified as pathogenic in previous reports, while c.675C>A and c.88 C > T were two novel variants which could lead to a premature termination codon (PTC) and resulted in loss of SUN5, and may also be pathogenic. SUN5 mRNA and protein were present at very low levels in ASS patients with SUN5 nonsense mutation. Furthermore, the distribution of outer dense fiber protein 1 (ODF1) and Nesprin3 was altered in sperm of ASS patients with SUN5 variants. The co-immunoprecipitation analysis indicated that SUN5 and ODF1, SUN5 and Nesprin3, and ODF1 and Nesprin3 interacted with each other in transfected HEK293T cells. Thus, we propose that SUN5, Nesprin3, and ODF1 may form a "triplet" structure through interactions at neck of sperm. When gene variants resulted in a loss of SUN5, the "triplet" structure disappears and then the head-tail junction becomes fragile, leading to the occurrence of ASS.
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http://dx.doi.org/10.1093/molehr/gaab028DOI Listing
April 2021

MAPLE: A Microbiome Analysis Pipeline Enabling Optimal Peptide Search and Comparative Taxonomic and Functional Analysis.

J Proteome Res 2021 Apr 13. Epub 2021 Apr 13.

Department of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Baltimore, Maryland 21201, United States.

Metaproteomics by mass spectrometry (MS) is a powerful approach to profile a large number of proteins expressed by all organisms in a highly complex biological or ecological sample, which is able to provide a direct and quantitative assessment of the functional makeup of a microbiota. The human gastrointestinal microbiota has been found playing important roles in human physiology and health, and metaproteomics has been shown to shed light on multiple novel associations between microbiota and diseases. MS-powered proteomics generally relies on genome data to define search space. However, metaproteomics, which simultaneously analyzes all proteins from hundreds to thousands of species, faces significant challenges regarding database search and interpretation of results. To overcome these obstacles, we have developed a user-friendly microbiome analysis pipeline (MAPLE, freely downloadable at http://maple.rx.umaryland.edu/), which is able to define an optimal search space by inferring proteomes specific to samples following the principle of parsimony. MAPLE facilitates highly comparable or better peptide identification compared to a sample-specific metagenome-guided search. In addition, we implemented an automated peptide-centric enrichment analysis function in MAPLE to address issues of traditional protein-centric comparison, enabling straightforward and comprehensive comparison of taxonomic and functional makeup between microbiota.
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http://dx.doi.org/10.1021/acs.jproteome.1c00114DOI Listing
April 2021

Systematic Merging of Nonfullerene Acceptor π-Extension and Tetrafluorination Strategies Affords Polymer Solar Cells with >16% Efficiency.

J Am Chem Soc 2021 Apr 13. Epub 2021 Apr 13.

Department of Chemistry, the Center for Light Energy Activated Redox Processes (LEAP), and the Materials Research Center (MRC), Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, United States.

The end-capping group (EG) is the essential electron-withdrawing component of nonfullerene acceptors (NFAs) in bulk heterojunction (BHJ) organic solar cells (OSCs). To systematically probe the impact of two frequent EG functionalization strategies, π-extension and halogenation, in A-DAD-A type NFAs, we synthesized and characterized four such NFAs: , , , and . To assess the relative importance of these strategies, we contrast these NFAs with the baseline acceptors, and . Up to 16.6% power conversion efficiency (PCE) in binary inverted OSCs with - combining π-extension and halogenation was achieved. When these two factors are combined, the effect on optical absorption is cumulative. Single-crystal π-π stacking distances are similar for the EG strategies of π-extension. Increasing the alkyl substituent length from to significantly alters the packing motif and eliminates the EG core interactions of . Electronic structure computations reveal some of the largest NFA π-π electronic couplings observed to date, 103.8 meV in and 47.5 meV in . Computed electronic reorganization energies, 132 and 133 meV for and , respectively, are also lower than Y6 (150 meV). BHJ blends show preferential π-face-on orientation, and both fluorination and π-extension increase NFA crystallinity. Femto/nanosecond transient absorption spectroscopy (fs/nsTA) and integrated photocurrent device analysis (IPDA) indicate that π-extension modifies the phase separation to enhance film ordering and carrier mobility, while fluorination suppresses unimolecular recombination. This systematic study highlights the synergistic effects of NFA π-extension and fluorination in affording efficient OSCs and provides insights into designing next-generation materials.
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http://dx.doi.org/10.1021/jacs.1c00211DOI Listing
April 2021

Ammonium Intercalation Induced Expanded 1T-Rich Molybdenum Diselenides for Improved Lithium Ion Storage.

ACS Appl Mater Interfaces 2021 Apr 13. Epub 2021 Apr 13.

Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), Nanjing 211816, P. R. China.

Transition metal dichalcogenides (TMDs), particularly molybdenum diselenides (MoSe), have the merits of their unique two-dimensional (2D) layered structures, large interlayer spacing (∼0.64 nm), good electrical conductivities, and high theoretical capacities when applied in lithium-ion batteries (LIBs) as anode materials. However, MoSe remains suffering from inferior stability as well as unsatisfactory rate capability because of the unavoidable volume expansion and sluggish charge transport during lithiation-delithiation cycles. Herein, we develop a simultaneous reduction-intercalation strategy to synthesize expanded MoSe (e-MoSe) with an interlayer spacing of 0.98 nm and a rich 1T phase (53.7%) by rationally selecting the safe precursors of ethylenediamine (NHCHNH), selenium dioxide (SeO), and sodium molybdate (NaMoO). It is noteworthy that NHCHNH can effectively reduce SeO and MoO forming MoSe nanosheets; in the meantime, the generated ammonium (NH) efficiently intercalates between MoSe layers, leading to charge transfer, thus stabilizing 1T phases. The obtained e-MoSe exhibits high capacities of 778.99 and 611.40 mAh g at 0.2 and 1 C, respectively, together with excellent cycling stability (retaining >90% initial capacity at 0.2 C over 100 charge-discharge cycles). It is believed that the material design strategy proposed in this paper provides a favorable reference for the synthesis of other transition metal selenides with improved electrochemical performance for battery applications.
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http://dx.doi.org/10.1021/acsami.0c22923DOI Listing
April 2021

Joint effects of HPV-related knowledge and socio-demographic factors on HPV testing behaviour among females in Shenzhen.

Eur J Public Health 2021 Apr 13. Epub 2021 Apr 13.

Department of Healthcare, Affiliated Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Shenzhen, China.

Background: Limited population-based studies explore the utilization and associated barriers or facilitators to cervical cancer screening in China. We attempted to investigate the associations of socio-demographic factors, HPV specific knowledge with HPV testing behaviour in Shenzhen, China.

Methods: A citywide cross-sectional survey was conducted from January to June 2015 in Shenzhen city by using a multistage stratified cluster sampling method. Socio-demographic information, awareness and specific knowledge of HPV, practice of HPV testing, and HPV vaccination-related attitude were collected. Multivariate logistic regression model was used to analyse possible associations.

Results: Approximately one third of total 8639 women aged from 30 to 60 years old had ever received HPV testing. Overall, 67.6% of all participants demonstrated low knowledge level of HPV. High HPV knowledge level was significantly associated with HPV testing behaviour (odds ratio: 3.792, 95% confidence interval: 3.400-4.230). The impact of residence and education on testing behaviour only turned to be significant if women had low level of HPV knowledge (P for multiplicative interactions: 0.001 and <0.001, respectively), whereas monthly income exerted promotion effects apparently among those with high knowledge level (P for multiplicative interaction: 0.037).

Conclusions: Our study revealed gaps in HPV knowledge and screening participation among Chinese women, and provided novel clues that women with high HPV knowledge level would be more appeal to involve in HPV testing behaviour. The influence of HPV-related knowledge on HPV testing also lies in the joint effects with socio-demographic factors, including residence, education and monthly income.
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http://dx.doi.org/10.1093/eurpub/ckab049DOI Listing
April 2021

The critical role of background rates of possible adverse events in the assessment of COVID-19 vaccine safety.

Vaccine 2021 Mar 6. Epub 2021 Mar 6.

The Mayo Clinic, United States.

Beginning in December of 2019, a novel coronavirus, SARS-CoV-2, emerged in China and is now a global pandemic with extensive morbidity and mortality. With the emergence of this threat, an unprecedented effort to develop vaccines against this virus began. As vaccines are now being introduced globally, we face the prospect of millions of people being vaccinated with multiple types of vaccines many of which use new vaccine platforms. Since medical events happen without vaccines, it will be important to know at what rate events occur in the background so that when adverse events are identified one has a frame of reference with which to compare the rates of these events so as to make an initial assessment as to whether there is a potential safety concern or not. Background rates vary over time, by geography, by sex, socioeconomic status and by age group. Here we describe two key steps for post-introduction safety evaluation of COVID-19 vaccines: Defining a dynamic list of Adverse Events of Special Interest (AESI) and establishing background rates for these AESI. We use multiple examples to illustrate use of rates and caveats for their use. In addition we discuss tools available from the Brighton Collaboration that facilitate case evaluation and understanding of AESI.
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http://dx.doi.org/10.1016/j.vaccine.2021.03.016DOI Listing
March 2021

Incidence of chronic thromboembolic pulmonary hypertension in Taiwan.

J Formos Med Assoc 2021 Apr 9. Epub 2021 Apr 9.

Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.

Background: The diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) is complex, and the modality of treatment is surgery and targeted medication. Patients with CTEPH could have a poor prognosis if their diagnosis or treatment is delayed. The incidence of CTEPH and its clinical features are largely unknown in Taiwan, even among other Asian populations. In this study, we aimed to investigate the geodemographics of CTEPH in Taiwan and describe the practical management and treatment outcomes in patients with CTEPH.

Methods: This study retrospectively enrolled patients in the Taiwan cohort - Registry of CTEPH. The study was conducted over 2 years inclusive of follow-up. The enrolment criteria depended on the current global guideline.

Results: From January 2018 to March 2020, 107 CTEPH patients enrolled in the Taiwan registry. All patients received right heart catheterisation examinations. The overall median age was 61.4 ± 16.5 years, and the cohort was dominated by female patients (75/107). Risk factors included pulmonary embolism (81.3%), deep vein thrombosis (22.4%), and previous major surgery (20.6%). Twenty-one (19.6%) patients underwent pulmonary endarterectomy operation alone, and 38 (35.5%) patients underwent balloon pulmonary angioplasty alone.

Conclusion: To our knowledge, this is the first national cohort study that demonstrated the raw CTEPH incidence in Taiwan. It also showed the CTEPH incidence between male and female patients in the Asian population was different from the Caucasian population.
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http://dx.doi.org/10.1016/j.jfma.2021.03.022DOI Listing
April 2021

Thioacetamide-induced norepinephrine production by hepatocytes is associated with hepatic stellate cell activation and liver fibrosis.

Curr Mol Pharmacol 2021 Apr 12. Epub 2021 Apr 12.

Department of Molecular Medicine, Beckman Research Institute of City of Hope, and Department of Pathology, City of Hope National Medical Center, Duarte, California. United States.

Background: Collagen production by activated hepatic stellate cells (HSCs) to encapsulate injury is part of the natural wound-healing response in injured liver. However, persistent activation of HSCs can lead to pathological fibrogenesis. Such persistent HSC activation could be mediated by norepinephrine (NE), a reaction product of dopamine beta-hydroxylase (DBH).

Objective: To investigate the potential paracrine role of NE in hepatotoxin thioacetamide (TAA)-induced liver fibrosis.

Methods/results: In TAA-treated mice, fibrotic liver tissue showed significant increases in the mRNA expression of DBH up to 14-fold and collagen up to 7-fold. Immunohistochemical staining showed increased DBH protein expression in fibrotic liver tissue. Parenchymal hepatocyte cell line HepG2 expressed DBH and secreted NE, and the conditioned medium of HepG2 cells promoted collagenesis in nonparenchymal HSC cell line LX-2. TAA treatment increased DBH expression by 170% in HepG2 cells, as well as increased NE by 120% in the conditioned medium of HepG2 cells. The conditioned medium of TAA-treated HepG2 cells was used to culture LX-2 cells, and was found to increase collagen expression by 80% in LX-2 cells. Collagen expression was reduced by pre-treating HepG2 cells with siRNA targeting DBH or by adding NE antagonists to the conditioned medium. Finally, TAA-induced oxidative stress in HepG2 cells was associated with induction of DBH expression.

Conclusion: Collectively, our results suggest a potential role for DBH/NE-mediated crosstalk between hepatocytes and HSCs in fibrogenesis. From a therapeutic standpoint, antagonism of DBH/NE induction in hepatocytes might be a useful strategy to suppress pathological fibrogenesis.
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http://dx.doi.org/10.2174/1874467214666210412144416DOI Listing
April 2021

Synthesis and biological evaluation of phenothiazine derivative-containing hydroxamic acids as potent class II histone deacetylase inhibitors.

Eur J Med Chem 2021 Apr 1;219:113419. Epub 2021 Apr 1.

Ph.D. Program in Drug Discovery and Development Industry, College of Pharmacy, Taipei Medical University, Taipei, Taiwan; Graduate Institute of Pharmacognosy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. Electronic address:

The pathogenesis of Alzheimer's disease (AD) has been associated with dysregulation of histone deacetylases (HDACs). Previously, acridine-based HDAC inhibitors have shown potential in ameliorating HDAC activity and enhancing neurite outgrowth. In this study, the acridine ring was modified using various phenothiazine derivatives. Several resulting compounds exhibited potent enzyme-inhibiting activity towards class II HDACs when compared to the clinically approved HDAC inhibitor SAHA. Compound 4f demonstrated the highest class II HDAC inhibition (IC = 4.6-600 nM), as well as promotion of neurite outgrowth. Importantly, compound 4f displayed no cytotoxicity against neuron cells. Compound 4f was further evaluated for cellular effects. Altogether, these findings show a potential strategy in HDAC inhibition for treatment of the neurological disease.
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http://dx.doi.org/10.1016/j.ejmech.2021.113419DOI Listing
April 2021

Case Report: Coinheritance of Germline Mutations in and in Colorectal Cancer.

Front Oncol 2021 25;11:658389. Epub 2021 Mar 25.

Department of Oncology, Nanjing Tongren Hospital, Nanjing, China.

Deleterious mutations in gene cause the autosomal dominant familial adenomatous polyposis (FAP) which is typically characterized by the occurrence of hundreds to thousands of colorectal adenomas that eventually lead to colorectal cancers (CRCs). are the two major susceptibility genes for breast and ovarian cancers. Here, we reported a coinheritance of mutations in and genes in a 20-year-old CRC patient with typical clinical features for FAP. Multiple relatives in the family of the patient were affected by colorectal and other cancers. Next-generation sequencing analysis using a panel consisting of 53 hereditary cancer related genes revealed a maternally inherited (exon15cn_del) mutation and a paternally inherited (p.lle1824AspfsX3) mutation. This is the first coexistence of and mutations in a CRC patient with the mutation inheritance pattern comprehensively characterized in the family. The patient underwent a colonoscopy and a subtotal colectomy and was subsequently diagnosed with colonic adenocarcinomas accompanied with hundreds of tubulovillous adenomas. The case reveals the scenario where two disease-causing mutations of different hereditary tumor syndromes coexist, and illustrates the importance of evaluating detailed family history and performing a multiple-gene panel test in patients with hereditary cancer.
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http://dx.doi.org/10.3389/fonc.2021.658389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8030582PMC
March 2021

T1a triple negative breast cancer has the worst prognosis among all the small tumor (<1 cm) of TNBC and HER2-rich subtypes.

Gland Surg 2021 Mar;10(3):943-952

Department of Breast Surgery, Peking Union Medical College Hospital, Beijing, China.

Background: Triple negative breast cancer (TNBC), accounting for 15% of all breast cancer cases, was usually considered as the most aggressive subtype. The present study evaluated the prognosis of T1a TNBC and the impact of tumor size on T1 TNBC survival in large-scale population.

Methods: This retrospective study enrolled T1a/T1b/T1c TNBC and HER2/hormone receptor (HoR) patients diagnosed between 2010 to 2012 from the Surveillance, Epidemiology, and End Results database. The following information was extracted for further analyses: demographic variables including age at diagnosis, race, marital status, laterality, histological grade, T/N stage, American Joint Committee on Cancer (AJCC) stage, radiation therapy, survival and cause of death. Kaplan-Meier method and Cox regression were engaged for breast cancer specific survival (BCSS) and overall survival (OS) analyses.

Results: In all, the present study enrolled 6,953 TNBC and 2,648 HER2/HoR patients. T1a TNBC which generally omitted adjuvant chemotherapy had worse prognosis than T1a HER2/HoR [BCSS: hazard ratio (HR) 3.23, 95% confidence interval (CI): 1.05-9.09, P=0.03; OS: HR 2.63, 95% CI: 1.25-5.56, P=0.01] and T1b HER2/HoR (BCSS: HR 5.26, 95% CI: 1.61-16.7, P=0.006; OS: HR 3.03, 95% CI: 1.27-7.14, P=0.013) tumors which both were recommended by the National Comprehensive Cancer Network (NCCN) guideline to have chemotherapy. T1a TNBC also showed a trend with poorer prognosis than T1b TNBC, but did not reach statistical significance.

Conclusions: T1a TNBC had the worst prognosis among all small tumors (<1 cm) of TNBC and HER2/HoR subtypes, indicating the necessity of more intensive adjuvant treatment.
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http://dx.doi.org/10.21037/gs-20-762DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033067PMC
March 2021

Stiffness of aortic arch and carotid arteries increases in -knockout mice with high-fat diet: evidence from echocardiography.

Am J Transl Res 2021 15;13(3):1352-1364. Epub 2021 Mar 15.

Department of Medicine, University of Illinois at Chicago Chicago, IL 60612, USA.

Arterial stiffness is an effective predictor of atherosclerosis. Measurement of pulse-wave velocity (PWV) is a gold-standard approach to study arterial stiffness. This study aims to examine arterial stiffness and heart functions via echocardiography at an early stage of atherosclerosis. A model of atherosclerosis in -knockout ( ) mice fed on high-fat diet (HFD) was used, with normal chow diet (ND) as a control. Stiffness of aortic arch and carotid arteries and left ventricular (LV) systolic/diastolic functions were measured by echocardiography. The plasma cholesterol levels and atherosclerotic plaque areas in the aortas were measured. The PWV values of aortic arch and carotid arteries were compared at 2, 4, 6 and 8 weeks with different diets. Compared with ND mice, PWV values in aortic arch and carotid arteries were significantly increased in HFD mice after 8 weeks (Aortic arch: 516.65 ± 216.89 cm/s vs. 192.53 ± 71.71 cm/s; Carotid arteries: 514.26 ± 211.01 cm/s vs. 188.03 ± 75.14 cm/s, respectively; both < 0.01) accompanied by the decrease in LV systolic/diastolic functions. These were well correlated with the increase in plasma cholesterol levels. Echo-based PWV measurement in the aortic arch was found more sensitive to predict atherosclerosis than in the carotid arteries in mice. Measuring aortic arch PWV via echocardiography could represent a new diagnostic strategy for early detection of atherosclerosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014403PMC
March 2021

Irradiated whole-cell vaccine suppresses hepatocellular carcinoma growth in mice via Th9 cells.

Oncol Lett 2021 May 22;21(5):409. Epub 2021 Mar 22.

Central Laboratory, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.

Liver cancer is one of the most common malignant tumors with no available satisfactory treatment. The aim of the present study was to investigate the anti-tumor effect of an irradiated hepatocellular carcinoma (HCC) whole-cell vaccine and its underlying mechanisms. Hepa1-6 and H22 HCC cell lines were irradiated in preparation for whole-cell vaccine production. Subsequently, two HCC tumor-bearing mouse models were created by injecting these Hepa1-6 and H22 cells into the abdominal skin of C57BL/6 and ICR mice, respectively. The mice were immunized with the corresponding whole-cell vaccine the next day, and then once a week until the end of the experimental period. Tumor growth, blood T helper (Th)9 cells and plasma interleukin (IL)-9 levels were monitored during the immunization period. Th9 cells were also induced by co-culture of the whole-cell vaccine with lymphocytes from the spleen and lymph nodes of the corresponding mice. Alterations of gene expression in transcription factor (TF) were determined by reverse transcription-quantitative PCR, and Th9 cells were detected using flow cytometry. The whole-cell vaccine effectively suppressed HCC tumor growth, as indicated by slower tumor growth and a smaller tumor size in the immunized group compared with the control. The percentage of blood Th9 cells and the concentration of plasma IL-9 were significantly increased in the immunized group. The whole-cell vaccine also induced Th9 cell differentiation and upregulated the expression of TFs PU.1, interferon regulatory factor 4 and basic leucine zipper transcriptional factor ATF-like. These results suggest that the irradiated HCC whole-cell vaccine inhibited tumor growth by increasing Th9 cell numbers in HCC mice.
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http://dx.doi.org/10.3892/ol.2021.12670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020379PMC
May 2021

Up-Regulation of Glycogen Synthesis and Degradation Enzyme Level Maintained Myocardial Glycogen in Huddling Brandt's Voles Under Cool Environments.

Front Physiol 2021 26;12:593129. Epub 2021 Mar 26.

College of Life Sciences, Qufu Normal University, Qufu, China.

Small mammals exhibit limited glucose use and glycogen accumulation during hypothermia. Huddling is a highly evolved cooperative behavioral strategy in social mammals, allowing adaptation to environmental cooling. However, it is not clear whether this behavior affects the utilization of glycogen in cold environments. Here, we studied the effects of huddling on myocardial glycogen content in Brandt's voles () under a mild cold environment (15°C). Results showed that (1) Compared to the control (22°C) group (CON), the number of glycogenosomes more than tripled in the cool separated group (CS) in both males and females; whereas the number of glycogenosomes increased in females but was maintained in males in the cool huddling group (CH). (2) Glycogen synthase (GS) activity in the CS group remained unchanged, whereas glycogen phosphorylase (GYPL) activity decreased, which mediated the accumulation of glycogen content of the CS group. (3) Both GS and GYPL activity increased which may contribute to the stability of glycogen content in CH group. (4) The expression levels of glucose transporters GLUT1 and GLUT4 increased in the CS group, accompanied by an increase in glucose metabolism. These results indicate that the reduced glycogen degradation enzyme level and enhanced glucose transport may lead to an increase in myocardial glycogen content of the separated voles under cool environment; while the up-regulation of glycogen synthesis and degradation enzyme level maintained myocardial glycogen content in the huddling vole.
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http://dx.doi.org/10.3389/fphys.2021.593129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033036PMC
March 2021

Circularly polarized luminescence from organic micro-/nano-structures.

Light Sci Appl 2021 Apr 12;10(1):76. Epub 2021 Apr 12.

State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM) & Institute of Flexible Electronics (Future Technology), Nanjing University of Posts & Telecommunications (NUPT), 9 Wenyuan Road, 210023, Nanjing, Jiangsu, China.

Circularly polarized light exhibits promising applications in future displays and photonic technologies. Circularly polarized luminescence (CPL) from chiral luminophores is an ideal approach to directly generating circularly polarized light, in which the energy loss induced by the circularly polarized filters can be reduced. Among various chiral luminophores, organic micro-/nano-structures have attracted increasing attention owing to the high quantum efficiency and luminescence dissymmetry factor. Herein, the recent progress of CPL from organic micro-/nano-structures is summarized. Firstly, the design principles of CPL-active organic micro-/nano-structures are expounded from the construction of micro-/nano-structure and the introduction of chirality. Based on these design principles, several typical organic micro-/nano-structures with CPL activity are introduced in detail, including self-assembly of small molecules, self-assembly of π-conjugated polymers, and self-assembly on micro-/nanoscale architectures. Subsequently, we discuss the external stimuli that can regulate CPL performance, including solvents, pH value, metal ions, mechanical force, and temperature. We also summarize the applications of CPL-active materials in organic light-emitting diodes, optical information processing, and chemical and biological sensing. Finally, the current challenges and prospects in this emerging field are presented. It is expected that this review will provide a guide for the design of excellent CPL-active materials.
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http://dx.doi.org/10.1038/s41377-021-00516-7DOI Listing
April 2021

Development of DNA-compatible hydroxycarbonylation reactions using chloroform as a source of carbon monoxide.

Bioorg Med Chem 2021 Mar 26;38:116118. Epub 2021 Mar 26.

HitGen Inc., Building 6, No. 8 Huigu 1(st) East Road, Tianfu International Bio-Town, Shuangliu District, Chengdu 610200, Sichuan, PR China. Electronic address:

A robust palladium-catalyzed hydroxycarbonylation of aryl halides on DNA has been developed. Instead of Mo(CO) as a source of carbon monoxide as previously described in the literature, chloroform was used as a surrogate in this report for the purpose of avoiding to use a large excess of molybdenum reagent which is not totally soluble in aqueous reaction mixtures.
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http://dx.doi.org/10.1016/j.bmc.2021.116118DOI Listing
March 2021

A facile method for vancomycin C-terminus functionalization and derivatization through hydrazide.

Bioorg Med Chem Lett 2021 Apr 8:128027. Epub 2021 Apr 8.

School of Pharmacy, Jinzhou Medical University, Jinzhou 121001, PR China. Electronic address:

Over 60-year clinical use of vancomycin led to the emergence of vancomycin-resistant bacteria and threatened our health. To combat vancomycin-resistant strains, numerous vancomycin analogues were developed, such as Telavancin, Oritavancin and Dalbavancin. Extra structures embedded on C-terminus has been proved to be an effective strategy to promote antibacterial activity of vancomycin against vancomycin-resistant strains. Here, we reported a facile strategy, inspired by native chemical ligation, for vancomycin C-terminus functionalization and derivatization. The introduction of C-terminal hydrazide on vancomycin not only provided us an accessible method for C-terminus functionalization through carbonyl azide and thioester, also acted as an efficient site for vancomycin structure modifications. Based on hydrazide-vancomycin, we effectively conjugated cysteine and cysteine containing peptides onto vancomycin C-terminus, and two fluorescent FITC-vancomycin were prepared through Cys-Maleimide conjugation. Meanwhile, we introduced lipophilic structures onto vancomycin C-terminus via the hydrazide moiety. The obtained vancomycin derivatives were evaluated against both Gram-positive and negative bacteria strains.
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http://dx.doi.org/10.1016/j.bmcl.2021.128027DOI Listing
April 2021

Limited efficacy with additional adverse effect of anti-adhesion barrier at primary cesarean section.

J Formos Med Assoc 2021 Apr 7. Epub 2021 Apr 7.

Department of Obstetrics & Gynecology, MacKay Memorial Hospital, Taipei 104, Taiwan; MacKay Junior College of Medicine, Nursing and Management, New Taipei City 251, Taiwan; Department of Medicine, MacKay Medical College, New Taipei City 252, Taiwan. Electronic address:

Background/purpose: In our experience, adhesion after the primary CS is generally minimal or nonexistent. However, adhesion barriers users have experienced more febrile episodes that may require therapeutic antibiotics during the postcesarean period. We evaluated clinical efficacy of HA-CMC and ORC to prevent adhesion at secondary CS and the post-operative outcome at primary and secondary CS.

Methods: This retrospective study includes 199 Asian women undergoing primary and secondary cesarean section between January1, 2011, and September 31, 2019. We used linear and logistic regression to analyze risk factors of postcesarean fever. An interaction term analysis was performed to examine the effect of surgical site infection risk factors and use of adhesion barrier on postcesarean fever rates.

Results: We found that use of adhesion barrier at the primary cesarean section is associated with a significantly higher incidence of postcesarean fever (p = 0.045), which is an independent risk factor of postcesarean fever (adjusted hazard ratio (Adj-HR)= 3.53, 95% CI = 1.03-10.24, p = 0.045). The strongest risk factor for postcesarean fever is the use of anti-adhesion film during emergency cesarean section (p = 0.041). In the subgroup of labor before operation and emergency cesarean section, adhesion barrier user had significant higher risk of postcesarean fever than nonuser (p = 0.018, Adj-HR = 12.12, 95% CI = 1.53-95.78; emergency cesarean section: p = 0.016, Adj-HR = 12.71, 95% CI = 1.62-99.62).

Conclusion: Use of anti-adhesion films during emergency cases and with a significantly higher risk of postcesarean fever which potentially means increased risk of surgical site infection. Therefore, we do not suggest routine application of anti-adhesion films during cesarean deliveries especially in emergency cesarean section or in a woman having labor before operation.
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http://dx.doi.org/10.1016/j.jfma.2021.03.012DOI Listing
April 2021

Development of omics biomarkers for estrogen exposure using mRNA, miRNA and piRNAs.

Aquat Toxicol 2021 Mar 12;235:105807. Epub 2021 Mar 12.

US Environmental Protection Agency, Office of Research and Development, 26 W. Martin Luther King Dr., Cincinnati, OH 45268, United States. Electronic address:

The number of chemicals requiring risk evaluation exceeds our capacity to provide the underlying data using traditional methodology. This has led to an increased focus on the development of novel approach methodologies. This work aimed to expand the panel of gene expression-based biomarkers to include responses to estrogens, to identify training strategies that maximize the range of applicable concentrations, and to evaluate the potential for two classes of small non-coding RNAs (sncRNAs), microRNA (miRNA) and piwi-interacting RNA (piRNA), as biomarkers. To this end larval Pimephales promelas (96 hpf +/- 1h) were exposed to 5 concentrations of 17α- ethinylestradiol (0.12, 1.25, 2.5, 5.0, 10.0 ng/L) for 48 h. For mRNA-based biomarker development, RNA-seq was conducted across all concentrations. For sncRNA biomarkers, small RNA libraries were prepared only for the control and 10.0 ng/L EE2 treatment. In order to develop an mRNA classifier that remained accurate over the range of exposure concentrations, three different training strategies were employed that focused on 10 ng/L, 2.5 ng/L or a combination of both. Classifiers were tested against an independent test set of individuals exposed to the same concentrations used in training and subsequently against concentrations not included in model training. Both random forest (RF) and logistic regression with elastic net regularizations (glmnet) models trained on 10 ng/L EE2 performed poorly when applied to lower concentrations. RF models trained with either the 2.5 ng/L or combination (2.5 + 10 ng/L) treatments were able to accurately discriminate exposed vs. non-exposed across all but the lowest concentrations. glmnet models were unable to accurately classify below 5 ng/L. With the exception of the 10 ng/L treatment, few mRNA differentially expressed genes (DEG) were observed, however, there was marked overlap of DEGs across treatments. Overlapping DEGs have well established linkages to estrogen and several of the 81 DEGs identified in the 10 ng/L treatment have been previously utilized as estrogenic biomarkers (vitellogenin, estrogen receptor-β). Following multiple test correction, no sncRNAs were found to be differentially expressed, however, both miRNA and piRNA classifiers were able to accurately discriminate control and 10 ng/L exposed organisms with AUCs of 0.83 and 1.0 respectively. We have developed a highly discriminative estrogenic mRNA biomarker that is accurate over a range of concentrations likely to be found in real-world exposures. We have demonstrated that both miRNA and piRNA are responsive to estrogenic exposure, suggesting the need to further investigate their regulatory roles in the estrogenic response.
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March 2021

AFB-induced mice liver injury involves mitochondrial dysfunction mediated by mitochondrial biogenesis inhibition.

Ecotoxicol Environ Saf 2021 Apr 7;216:112213. Epub 2021 Apr 7.

Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, China.

Aflatoxin B1 (AFB) pollutes foodstuffs and feeds, causing a food safety problem and seriously endangering human and animal health. Liver is the principal organ for AFB accumulation and biotransformation, during which AFB can cause acute and chronic liver damage, however, the specific mechanism is not completely clear. Mitochondria are the primary organelle of cellular bio-oxidation, providing 95% energy for liver to execute its multiple functions. Therefore, we speculated that mitochondrial dysfunction is involved in AFB-induced liver injury. To verify the hypothesis, a total of eighty healthy male mice were randomly divided into four groups on average, and exposed with 0, 0.375, 0.75 and 1.5 mg/kg body weight AFB by intragastric administration for 30 d. The results displayed that AFB triggered liver injury accompanied by oxidative stress. AFB exposure also damaged mitochondria structure, decreased mitochondrial membrane potential (MMP), as well as increased cytoplasmic cytochrome c (Cyt-c) protein expression, Bax, p53, Caspase-3/9 protein and/or mRNA expression levels and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine-5'-triphosphate (dUTP) nick end labeling (TUNEL) staining positive cells in mice liver. Meanwhile, AFB exposure elevated pyruvate content, inhibited tricarboxylic acid (TCA) cycle rate-limiting enzymes and electron transport chain (ETC) complexes I-V activities, disturbed ETC complexes I-V subunits mRNA expression levels and reduced adenosine triphosphate (ATP) level in mice liver. These results indicated that AFB destroyed mitochondrial structure, activated mitochondrion-dependent apoptosis and induced mitochondrial dysfunction. In addition, AFB disrupted mitochondrial biogenesis, presented as the abnormalities of protein and/or gene expression levels of voltage dependent anion channel protein 1 (VDAC1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (Nrf1) and mitochondrial transcription factor A (Tfam). This may contribute to hepatic and mitochondrial lesions induced by AFB. These results provide a new perspective for elucidating the mechanisms of AFB hepatotoxicity.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112213DOI Listing
April 2021