Publications by authors named "Weimin Zhang"

395 Publications

Nanozyme Applications: A Glimpse of Insight in Food Safety.

Front Bioeng Biotechnol 2021 24;9:727886. Epub 2021 Aug 24.

College of Food Science and Engineering, Hainan University, Haikou, China.

Nanozymes own striking merits, including high enzyme-mimicking activity, good stability, and low cost. Due to the powerful and distinguished functions, nanozymes exhibit widespread applications in the field of biosensing and immunoassay, attracting researchers in various fields to design and engineer nanozymes. Recently, nanozymes have been innovatively used to bridge nanotechnology with analytical techniques to achieve the high sensitivity, specificity, and reproducibility. However, the applications of nanozymes in food applications are seldom reviewed. In this review, we summarize several typical nanozymes and provide a comprehensive description of the history, principles, designs, and applications of nanozyme-based analytical techniques in food contaminants detection. Based on engineering and modification of nanozymes, the food contaminants are classified and then discussed in detail via discriminating the roles of nanozymes in various analytical methods, including fluorescence, colorimetric and electrochemical assay, surface-enhanced Raman scattering, magnetic relaxing sensing, and electrochemiluminescence. Further, representative examples of nanozymes-based methods are highlighted for contaminants analysis and inhibition. Finally, the current challenges and prospects of nanozymes are discussed.
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http://dx.doi.org/10.3389/fbioe.2021.727886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421533PMC
August 2021

Calcium chelator BAPTA‑AM protects against iron overload‑induced chondrocyte mitochondrial dysfunction and cartilage degeneration.

Int J Mol Med 2021 10 1;48(4). Epub 2021 Sep 1.

Department of Spine Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China.

Osteoarthritis (OA) is a common joint disease that is characterized by cartilage degradation. Iron deposition in the joints is common during the pathogenic progression of OA and recent studies have indicated that iron overload is an important contributor to OA progression. Calcium chelators have been reported to inhibit iron influx via modulating transferrin receptor protein 1 internalization, and they have been identified as a potential approach to the treatment of iron overload‑induced diseases. The aim of the present study was to investigate the effect of calcium chelators on the progression of iron overload‑induced OA. Primary chondrocytes were treated with various concentrations of ferric ammonium citrate (FAC) to mimic iron overload , followed by co‑treatment with the calcium chelator BAPTA acetoxymethyl ester (BAPTA‑AM). Subsequently, intracellular iron levels, cell viability, reactive oxygen species (ROS) levels, mitochondrial function and morphological changes, as well as MMP levels, were detected using commercial kits. It was demonstrated that FAC treatment significantly promoted chondrocyte apoptosis and the expression of MMPs, and these effects were reversed by co‑treatment with BAPTA‑AM. Moreover, BAPTA‑AM suppressed iron influx into chondrocytes and inhibited iron overload‑induced ROS production and mitochondrial dysfunction. These results indicated that calcium chelators may be of value in the treatment of iron metabolism‑related diseases and iron overload‑induced OA progression.
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http://dx.doi.org/10.3892/ijmm.2021.5029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416145PMC
October 2021

NOX5 mediates the crosstalk between tumor cells and cancer-associated fibroblasts via regulating cytokine network.

Clin Transl Med 2021 Aug;11(8):e472

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China.

Activation of cancer-associated fibroblasts (CAFs) is a crucial feature for tumor malignancy. The reciprocal interplay between tumor cells and CAFs not only facilitates tumor progression and metastasis but also sustains the tumor-promoting function of CAFs. Nevertheless, how tumor cells readily adapt to these functional CAFs is still unclear. NADPH oxidase 5 (NOX5) is a strong reactive oxygen species producer overexpressed in esophageal squamous cell carcinoma (ESCC) cells. In this study, we showed that NOX5-positive ESCC cells induced normal fibroblasts (NFs) or adipose-derived mesenchymal stem cells (MSCs) to express the marker of CAFs-α smooth muscle actin. Moreover, these tumor cells reprogrammed the cytokine profile of the activated CAFs, which further stimulated NFs or MSCs to CAFs and induced lymphangiogenesis to facilitate ESCC malignancy. NOX5 activated intratumoral Src/nuclear factor-κB signaling to stimulate secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and lactate from tumor cells. Subsequently, TNF-α, IL-1β, and lactate activated CAFs, and facilitated the secretion of IL-6, IL-7, IL-8, CCL5, and transforming growth factor-β1 from CAFs. These CAFs-derived cytokines reciprocally induced the progression of NOX5-positive ESCC cells. Our findings together indicate that NOX5 serves as the driving oncoprotein to provide a niche that is beneficial for tumor malignant progression.
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http://dx.doi.org/10.1002/ctm2.472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329696PMC
August 2021

Genetic Features of Plasmid- and Chromosome-Mediated in Isolates From Animal Organs With Lesions.

Front Microbiol 2021 5;12:707332. Epub 2021 Aug 5.

College of Veterinary Medicine, Northwest A&F University, Yangling, China.

The genomic context of the gene in from animal feces has been widely reported. However, less is known about the -carrying plasmid characteristics and other functional regions of isolates from animal organs with lesions. The present study investigated the antimicrobial resistance, population structure, and genetic features of -positive strains isolated from animal organs with lesions. The antimicrobial susceptibility testing indicated that 24 -positive isolates were resistant to at least three or all antimicrobial categories. MLST analysis suggested that the dominant clone complexes (CC) were mainly CC156, CC448, and CC10. In addition, ST10596, a newly discovered sequence type in swine, failed to be classified. Meanwhile, the gene located on the different plasmids was successfully transferred to the recipients, and whole-genome sequencing indicated the gene was embedded in cassette but not flanked by IS. The gene is located on the chromosome and embedded in Tn. Furthermore, was found on the IncX3-type plasmid of J-8. The and gene of type IV secretion system (T4SS) were truncated by IS and IS and located on the IncX4- and the IncHI2/HI2A/N-type plasmids, respectively. The multidrug-resistant (MDR) region of IncHI2/HI2A/N-type plasmids contained two class 1 integrons (In, In) and four composite transposons (Tn, Tn, cn_4692_IS, cn_6354_IS). Overall, 24 -positive isolates in our study showed MDR, or even extensively drug resistant (XDR), and exhibited population diversity. The T4SS gene truncation by the insertion sequence may affect the efficiency of plasmid conjugative transfer. Furthermore, the class 1 integrons and composite transposons in the MDR region of IncHI2/HI2A/n-type plasmid contributed to the multireplicon plasmid formation, the acquisition, and transfer of antimicrobial resistance genes (ARGs).
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http://dx.doi.org/10.3389/fmicb.2021.707332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8386294PMC
August 2021

Characterization of the flavor and nutritional value of coconut water vinegar based on metabolomics.

Food Chem 2021 Aug 16;369:130872. Epub 2021 Aug 16.

School of Science, Hainan University, Haikou 570228, China; Key Laboratory of Food Nutrition and Functional Food of Hainan Province, Haikou 570228, China; Key Laboratory of Tropical Agricultural Products Processing Technology of Haikou City, Haikou 570228, China. Electronic address:

Tender Coconut water is popular for its deliciousness and nutrition. Mature coconut water, usually discarded as waste in the coconut kernel-based food industry due to its unpleasant flavor, was used as a raw material to make vinegar by liquid-state fermentation. The compounds in fresh coconut water with high odor activity values (OAVs) were isovaleric acid and acetic acid, with pungent sour tastes. The compounds with high OAVs in aged coconut water vinegar were phenylethyl acetate, isoamyl acetate and benzaldehyde, with almond, banana or pear-like aromas. Coconut water vinegar was rich in essential amino acids, especially phenylalanine. Through pathway analysis, seventeen key metabolic pathways and three key metabolic substrates (aspartate, glutamate and pyruvate) were found. According to sensory evaluation, the aged vinegar tastes better. Coconut water vinegar is delicious and nutritious, so reprocessing mature coconut water into vinegar is an appropriate way to reuse waste coconut water.
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http://dx.doi.org/10.1016/j.foodchem.2021.130872DOI Listing
August 2021

Two Foxo1 homologues in the orange-spotted grouper Epinephelus coioides: sequences, expression, and possible involvement in the activation of cyp19a1a expression in the ovary.

Fish Physiol Biochem 2021 Aug 21. Epub 2021 Aug 21.

Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, Sun Yat-Sen University, Guangzhou, 510275, People's Republic of China.

Foxo1, a member of Foxo transcription factor family, is involved in a number of physiological processes including metabolism, cell cycle progression, aging, and apoptosis. In the ovarian granulosa cell of mouse, Foxo1 is implicated to inhibit the expression of Cyp19a1, a gene encoding the aromatase that converts androgens into estrogens. Currently, the information about the expression and physiological relevance of Foxo1 homologues in the ovary of teleosts is scarce. In the present study, cDNAs encoding two forms of Foxo1, Foxo1a and Foxo1b, were isolated from the orange-spotted grouper. Phylogenetic analysis indicated that the orange-spotted groupers Foxo1a and Foxo1b were closely related to the counterparts of the ricefield eel. RT-PCR analysis showed that the orange-spotted groupers foxo1a and foxo1b were expressed in a wide range of tissues, with high levels detected in the brain regions, liver, and intestine. Quantitative real-time PCR analysis showed similar expression profiles for cyp19a1a, foxo1a, and foxo1b in the ovary during development from the primary growth to mature stages, with peak values detected at the vitellogenic stage. In situ hybridization detected mRNA of foxo1a, foxo1b, and cyp19a1a in granulosa cells surrounding vitellogenic oocytes. In vitro transfection showed that both Foxo1a and Foxo1b upregulated the orange-spotted grouper cyp19a1a promoter activities, possibly through the conserved Foxo binding site. Collectively, these results suggest that both Foxo1a and Foxo1b may be involved in the regulation of the ovarian functions in the orange-spotted grouper and the physiological roles of Foxo1 homologues in the ovary may be diversified in vertebrates.
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http://dx.doi.org/10.1007/s10695-021-01002-yDOI Listing
August 2021

The inhibitory effect Polygonum Cillinerve polysaccharide on transmissible gastroenteritis virus of swine.

Res Vet Sci 2021 Aug 8;140:47-55. Epub 2021 Aug 8.

College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, PR China. Electronic address:

Transmissible gastroenteritis virus of swine (TGEV) is one kind of the main pathogens causing viral diarrhea in pig. In this study, the inhibitory effect of Polygonum Cillinerve polysaccharide (PCP) on TGEV was studied. Firstly, MTT method was used to measure the cell viability of PCP. Then Hoechst 33258 fluorescence staining, Annexin V-FITC/PI fluorescence staining, real-time PCR and western blot were used to explore the effect of PCP on inhibiting TGEV. The results showed that PCP could significantly reduce the apoptosis rate induced by TGEV, reduce the expression of ROS, reduce TGEV replication, increase the expression levels of Bcl-2 and Bax genes, increase the expression of Bcl-2 protein, decreased the expression of Cyto c protein, and reduce the amount of cleaved caspase 3. Therefore, PCP had the better inhibitory effect on TGEV, which provided a certain theoretical basis for the prevention and treatment of TGEV.
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http://dx.doi.org/10.1016/j.rvsc.2021.08.005DOI Listing
August 2021

Characterization of novel gliotoxin biosynthesis-related genes from deep-sea-derived fungus Geosmithia pallida FS140.

Biochimie 2021 Aug 5;191:1-10. Epub 2021 Aug 5.

Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, State Key Laboratory of Applied Microbiology Southern China, Institute of Microbiology, Guangdong Academy of Sciences, China. Electronic address:

Gliotoxins are epipolythiodioxopiperazine toxins produced by the filamentous fungi, which show great potential in the treatment of liver and lung cancer because of its cytotoxicity. In this study, three novel genes related to gliotoxin biosynthesis, gliT, gliM and gliK encoding thioredoxin reductase, O-methyltransferase and gamma-glutamyl cyclotransferase, respectively, from the deep-sea-derived fungus Geosmithia pallida were cloned from G. pallida and expressed in Escherichia coli. The recombinant GliT, GliM and GliK proteins were expressed and purified by Ni affinity column, which was demonstrated by SDS-PAGE and Western blot analysis. The inclusion bodies of GliT were renatured and the corresponding enzymatic properties of the two enzymes were further investigated. Using DTNB as a substrate, GliT showed the highest enzymatic activity of 11041 mU/L at pH 7.0, and the optimal reaction temperature was 40 °C. Using EGCG as a substrate, GliM showed the highest enzymatic activity of 239.19 mU/mg at pH 7.0, the optimum temperature was 35 °C. GliK from G. pallida was firstly reported to show bi-function of glutymal cyclotransferase and acetyltransfearse actvity with highest enzymatic activity of 615.5 U/mg in this study. The results suggested the important enzymatic function of GliT, GliM and GliK in the gliotoxin biosynthesis in G. pallida, which would lay a foundation for the mechanism elucidation of the gliotoxin biosynthesis in G. pallida and the exploitation of novel gliotoxin derivaties.
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http://dx.doi.org/10.1016/j.biochi.2021.08.001DOI Listing
August 2021

MAGE-C3 promotes cancer metastasis by inducing epithelial-mesenchymal transition and immunosuppression in esophageal squamous cell carcinoma.

Cancer Commun (Lond) 2021 Aug 4. Epub 2021 Aug 4.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, 100142, P. R. China.

Background: Evading immune surveillance is necessary for tumor metastasis. Thus, there is an urgent need to better understand the interaction between metastasis and mechanisms of tumor immune evasion. In this study, we aimed to clarify a novel mechanism that link tumor metastasis and immunosuppression in the development of esophageal squamous cell carcinoma (ESCC).

Methods: The expression of melanoma-associated antigen C3 (MAGE-C3) was detected using immunohistochemistry. Transwell assays were used to evaluate the migration and invasion ability of esophageal squamous cell carcinoma (ESCC) cells. Metastasis assays in mice were used to evaluate metastatic ability in vivo. Lymphocyte-mediated cytotoxicity assays were performed to visualize the immune suppression function on tumor cells. RNA sequencing was performed to identify differentially expressed genes between MAGE-C3 overexpressing ESCC cells and control cells. Gene ontology (GO) enrichment analyses was performed to identify the most altered pathways influenced by MAGE-C3. The activation of the interferon-γ (IFN-γ) pathway was analyzed using Western blotting, GAS luciferase reporter assays, immunofluorescence, and flow cytometry. The role of MAGE-C3 in the IFN-γ pathway was determined by Western blotting and immunoprecipitation. Furthermore, immunohistochemistry and flow cytometry analysis monitored the changes of infiltrated T cell populations in murine lung metastases.

Results: MAGE-C3 was overexpressed in ESCC tissues. High expression of MAGE-C3 had a significant association with the risk of lymphatic metastasis and poor survival in patients with ESCC. Functional experiments revealed that MAGE-C3 promoted tumor metastasis by activating the epithelial-mesenchymal transition (EMT). MAGE-C3 repressed antitumor immunity and regulated cytokine secretion of T cells, implying an immunosuppressive function. Mechanistically, MAGE-C3 facilitated IFN-γ signaling and upregulated programmed cell death ligand 1 (PD-L1) by binding with IFN-γ receptor 1 (IFNGR1) and strengthening the interaction between IFNGR1 and signal transducer and activator of transcription 1 (STAT1). Interestingly, MAGE-C3 displayed higher tumorigenesis in immune-competent mice than in immune-deficient nude mice, confirming the immunosuppressive role of MAGE-C3. Furthermore, mice bearing MAGE-C3-overexpressing tumors showed worse survival and more lung metastases with decreased CD8 infiltrated T cells and increased programmed cell death 1 (PD-1) CD8 infiltrated T cells.

Conclusion: MAGE-C3 enhances tumor metastasis through promoting EMT and protecting tumors from immune surveillance, and could be a potential prognostic marker and therapeutic target.
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http://dx.doi.org/10.1002/cac2.12203DOI Listing
August 2021

Autophagy-Related Three-Gene Prognostic Signature for Predicting Survival in Esophageal Squamous Cell Carcinoma.

Front Oncol 2021 15;11:650891. Epub 2021 Jul 15.

Department of Oncology, Cancer Institute, Peking University Shenzhen Hospital, Shenzhen Peking University-Hong Kong University of Science and Technology (PKU-HKUST) Medical Center, Shenzhen, China.

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignant tumors in China, and its prognosis remains poor. Autophagy is an evolutionarily conserved catabolic process involved in the occurrence and development of ESCC. In this study, we described the expression profile of autophagy-related genes (ARGs) in ESCC and developed a prognostic prediction model for ESCC patients based on the expression pattern of ARGs. We used four ESCC cohorts, GSE53624 (119 samples) set as the discovery cohort, The Cancer Genome Atlas (TCGA) ESCC set (95 samples) as the validation cohort, 155 ESCC cohort, and Oncomine cohort were used to screen and verify differentially expressed ARGs. We identified 34 differentially expressed genes out of 222 ARGs. In the discovery cohort, we divided ESCC patients into three groups that showed significant differences in prognosis. Then, we analyzed the prognosis of 34 differentially expressed ARGs. Three genes [poly (ADP-ribose) polymerase 1 (PARP1), integrin alpha-6 (ITGA6), and Fas-associated death domain (FADD)] were ultimately obtained through random forest feature selection and were constructed as an ARG-related prognostic model. This model was further validated in TCGA ESCC set. Cox regression analysis confirmed that the three-gene signature was an independent prognostic factor for ESCC patients. This signature effectively stratified patients in both discovery and validation cohorts by overall survival ( = 5.162E-8 and = 0.052, respectively). We also constructed a clinical nomogram with a concordance index of 0.713 to predict the survival possibility of ESCC patients by integrating clinical characteristics and the ARG signature. The calibration curves substantiated fine concordance between nomogram prediction and actual observation. In conclusion, we constructed a new ARG-related prognostic model, which shows the potential to improve the ability of individualized prognosis prediction in ESCC.
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http://dx.doi.org/10.3389/fonc.2021.650891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8321089PMC
July 2021

Nr5a homologues in the ricefield eel Monopterus albus: Alternative splicing, tissue-specific expression, and differential roles on the activation of cyp19a1a promoter in vitro.

Gen Comp Endocrinol 2021 Oct 26;312:113871. Epub 2021 Jul 26.

Institute of Aquatic Economic Animals and Guangdong Province Key Laboratory for Aquatic Economic Animals, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China; Guangdong Provincial Engineering Technology Research Center for Healthy Breeding of Important Economic Fish, Sun Yat-Sen University, Guangzhou, China. Electronic address:

Nr5a (Fushi tarazu factor 1, Ftz-F1) homologues belong to the nuclear receptor superfamily, and are involved in the regulation of reproduction in vertebrates. Four genes encoding Nr5a homologues were present in the genome of ricefield eel, which are designated as nr5a1a, nr5a1b, nr5a2, and nr5a5 in the present study. Alternatively spliced transcripts were identified for nr5a1a and nr5a1b genes. Sequence analysis indicated that nr5a5 is possibly a paralog of nr5a2, and nr5a1b is lost during evolution in some teleosts including tilapia and medaka. Ricefield eel nr5a genes exhibit tissue-specific expression patterns, with nr5a1a and nr5a1b resembling that of the SF-1/Ad4BP (NR5A1) subfamily, and nr5a2 and nr5a5 resembling that of the NR5A2/LRH/FTF subfamily. Transcriptomic analysis revealed parallel expression profiles of nr5a1a, foxl2, and cyp19a1a in ovarian follicles during vitellogenesis, with peak values at the late vitellogenic stage. Real-time PCR indicated that the expression levels of nr5a1a and foxl2 in gonads were decreased significantly during the sexual transition from female to the late intersexual stage. In vitro transient transfection assay showed that Nr5a1a up-regulated ricefield eel cyp19a1a promoter activities synergistically with Foxl2. However, Nr5a1b, Nr5a2, and Nr5a5 could neither activate ricefield eel cyp19a1a promoter alone nor enhance the stimulatory effects of Foxl2 on cyp19a1a promoter activities. Collectively, the above data suggest that Nr5a homologues may have diverse and differential roles in the tissues of ricefield eels. The up-regulation of gonadal nr5a1a and foxl2 during vitellogenesis may be important for the ovarian development whereas their down-regulation during the sexual transition period may be important for the sex change process of ricefield eels, possibly through the regulation of cyp19a1a gene expression.
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http://dx.doi.org/10.1016/j.ygcen.2021.113871DOI Listing
October 2021

How Effective Is the Green Development Policy of China's Yangtze River Economic Belt? A Quantitative Evaluation Based on the PMC-Index Model.

Int J Environ Res Public Health 2021 07 19;18(14). Epub 2021 Jul 19.

School of Public Administration, Central China Normal University, Wuhan 430079, China.

Although many countries around the world, especially China, highlight the strategy of green development, there has been little research evaluating the effectiveness of green development policies in local area. This study explores 16 policy texts with the theme of green development in the Yangtze River Economic Belt in China. Using the Policy Modeling Consistency Index (PMC-Index) model, the paper establishes a multi-input-output policy table and scientifically and systematically evaluates these policies. The results show that the average PMC index of the 16 policy texts is 6.83, indicating a high overall quality of policy texts. The index identifies two states of policy effectiveness as being good and excellent; 50% of the total texts fall into these categories and do not fall into the category of having a low level of policy effectiveness. Five indicators, including policy timeliness, social benefits, policy audience scope, and incentives and constraints, significantly impact the PMC-Index of the policy. Six representative policy samples were selected and analyzed. The advantages and disadvantages of the policy can be more fully understood by the degree of depression of the PMC's three-dimensional curved surface (PMC-Surface) model. Finally, the paper provides theoretical recommendations for the optimization of the green development policies.
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http://dx.doi.org/10.3390/ijerph18147676DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8303228PMC
July 2021

Transcatheter Aortic Valve Implantation Assisted by Extracorporeal Membrane Oxygenation for the Treatment of Aortic Stenosis with Cardiogenic Shock.

Arq Bras Cardiol 2021 07;117(1 suppl 1):33-37

Departamento de Cirurgia Cardíaca, Hospital Sir Run Run Shaw, Escola de Medicina, Universidade de Zhejiang, Zhejiang - China.

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http://dx.doi.org/10.36660/abc.20201358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291898PMC
July 2021

Enzymatic browning in relation to permeation of oxygen into the kernel of postharvest areca nut under different storage temperatures.

Food Sci Nutr 2021 Jul 24;9(7):3768-3776. Epub 2021 May 24.

College of Food Science and Engineering Hainan University Haikou China.

Previous study indicates that kernel of areca nut is susceptible to enzymatic browning caused by phenolic oxidation, which involves the ingression of oxygen into interior tissue. However, the reason for permeation of oxygen into the interior of areca nut and its possible influencing factors (e.g., temperatures) are little known. In the present study, we set three storage temperatures (25, 10, and 5°C) and investigated the effects on kernel browning and related physic-biochemical and tissue morphological changes. The results showed that the most severe kernel browning was observed in areca nut stored at 25°C, followed by 5°C. Comparatively, a slower browning development was found in areca nut stored at 10°C. More serious kernel browning at 25 and 5°C might be attributed to increased membrane permeability and aggravated tissue damage in view of morphological observations on pericarp, mesocarp, and kernel shell. Higher lignin content and phenylalanine ammonia-lyase activity were observed in mesocarp of areca nuts stored at 25 and 5°C as compared to 10°C, indicating that mesocarp lignification could facilitate the permeability of oxygen. Furthermore, the data showed that storage at 25 and 5°C induced the higher polyphenol oxidase activity while accelerating the decline in total phenolic content in areca nut kernel, which could contribute to higher occurrence of enzymatic browning reaction compared to that at 10°C. These results suggest that natural senescence at 25°C and severe chilling stress at 5°C could be influencing factors triggering the permeation of oxygen, leading to internal kernel browning in areca nut.
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http://dx.doi.org/10.1002/fsn3.2341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269670PMC
July 2021

SNORA42 promotes oesophageal squamous cell carcinoma development through triggering the DHX9/p65 axis.

Genomics 2021 Sep 26;113(5):3015-3029. Epub 2021 Jun 26.

Research Center, the Fourth Hospital of Hebei Medical University, Shijiazhuang, 050011, Hebei, China. Electronic address:

Small nucleolar RNAs (snoRNAs) are an important group of non-coding RNAs that have been reported to play a key role in the occurrence and development of various cancers. Here we demonstrate that Small nucleolar RNA 42 (SNORA42) enhanced the proliferation and migration of Oesophageal squamous carcinoma cells (ESCC) via the DHX9/p65 axis. Our results found that SNORA42 was significantly upregulated in ESCC cell lines, tissues and serum of ESCC patients. The high expression level of SNORA42 was positively correlated with malignant characteristics and over survival probability of patients with ESCC. Through in vitro and in vivo approaches, we demonstrated that knockdown of SNORA42 significantly impeded ESCC growth and metastasis whereas overexpression of SNORA42 got opposite effects. Mechanically, SNORA42 promoted DHX9 expression by attenuating DHX9 transports into the cytoplasm, to protect DHX9 from being ubiquitinated and degraded. From the KEGG analysis of Next-Generation Sequencing, the NF-κB pathway was one of the most regulated pathways by SNORA42. SNORA42 enhanced phosphorylation of p65 and this effect could be reversed by NF-κB inhibitor, BAY11-7082. Moreover, SNORA42 activated NF-κB signaling through promoting the transcriptional co-activator DHX9 interacted with p-p65, inducing NF-κB downstream gene expression. In summary, our study highlights the potential of SNORA42 is up-regulated in ESCC and promotes ESCC development partly via interacting with DHX9 and triggering the DHX9/p65 axis.
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http://dx.doi.org/10.1016/j.ygeno.2021.06.036DOI Listing
September 2021

Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial.

Lancet Oncol 2021 08 23;22(8):1162-1174. Epub 2021 Jun 23.

Jiangsu Hengrui Pharmaceuticals, Shanghai, China.

Background: The addition of camrelizumab to gemcitabine and cisplatin showed promising activity as first-line therapy in patients with recurrent or metastatic nasopharyngeal carcinoma in a phase 1 trial. We therefore compared camrelizumab plus gemcitabine and cisplatin with placebo plus gemcitabine and cisplatin in a randomised phase 3 trial.

Methods: In this randomised, double-blind, phase 3 trial done at 28 hospitals in China, patients were eligible if they were aged 18-75 years, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and had previously untreated recurrent or metastatic nasopharyngeal carcinoma. Patients were randomly assigned (1:1; using an interactive web-response system with a block size of four) to receive either camrelizumab (200 mg on day 1) or matching placebo intravenously, plus gemcitabine and cisplatin (gemcitabine 1000 mg/m on days 1 and 8; cisplatin 80 mg/m on day 1) intravenously every 3 weeks for four to six cycles, followed by maintenance therapy with camrelizumab or placebo, until radiographic progression, unacceptable toxicity, start of new anticancer treatment, investigator decision, or withdrawal of consent. Stratification factors used in randomisation were liver metastases, previous radical concurrent chemoradiotherapy, and ECOG performance status. The allocation sequence was generated by an independent randomisation group. The primary endpoint was progression-free survival per independent review committee. The significance threshold for independent review committee-assessed progression-free survival was p=0·0086 (one-sided) at the interim analysis. Efficacy and safety analyses included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03707509, and is closed for enrolment but is ongoing.

Findings: Between Nov 13, 2018, and Nov 29, 2019, 343 patients were screened and 263 were eligible and were randomly assigned to the camrelizumab group (n=134) or placebo group (n=129). At the prespecified interim analysis (June 15, 2020), independent review committee-assessed progression-free survival was significantly longer in the camrelizumab group (median 9·7 months [95% CI 8·3-11·4]) than in the placebo group (median 6·9 months [5·9-7·3]; hazard ratio 0·54 [95% CI 0·39-0·76]; one-sided p=0·0002). As of Dec 31, 2020, the most common grade 3 or worse adverse events of any cause were decreased white blood cell count (89 [66%] of 134 patients in the camrelizumab group vs 90 [70%] of 129 patients in the placebo group), decreased neutrophil count (86 [64%] vs 85 [66%]), anaemia (53 [40%] vs 57 [44%]), and decreased platelet count (53 [40%] vs 52 [40%]). Serious adverse events were reported in 59 (44%) of 134 patients in the camrelizumab group and 48 (37%) of 129 patients in the placebo group. Treatment-related deaths occurred in five (4%) patients in the camrelizumab group (two unknown cause of death, one multiple organ dysfunction syndrome, one pharyngeal haemorrhage, and one arrhythmia) and one (<1%) patient in the placebo group (unknown cause of death).

Interpretation: Our findings suggest that camrelizumab plus gemcitabine and cisplatin could be a new standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma in the first-line setting. Longer follow-up is needed to confirm this conclusion.

Funding: Jiangsu Hengrui Pharmaceuticals (formerly Jiangsu Hengrui Medicine).

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(21)00302-8DOI Listing
August 2021

Food additives: From functions to analytical methods.

Crit Rev Food Sci Nutr 2021 Jun 1:1-21. Epub 2021 Jun 1.

School of Life and Health Sciences, The Chinese University of Hong Kong, Shenzhen, P.R. China.

Food additives refer to all kinds of trace substances used in food or food processing to preserve flavor or enhance food taste, appearance, or other qualities. At present, artificial synthetic food additives have gradually replaced the natural food additives and many problems related to food additives, involving the abuse of food additives, excessive additives or even toxic additives. Obviously, food additives can bring people great sensory enjoyment and commercial convenience, but they may also cause potential risks to human health. So, it is of high significance to conduct quantitative analysis on the content of food additives. According to their functions and the regulatory requirements of food additives, this review starts from the classification and structures of various food additives involving colorants, preservatives, antioxidants, sweeteners, emulsifiers, stabilizers, thickeners, gelling agents. It then summarizes and discusses analytical methods for quantification of food additives including modern immunoassays and other biotechnological methods. The proposed review aspires to fill in the knowledge gap of food additives between academia and industry by covering all kinds of analytical methods for quantifying food additives.
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http://dx.doi.org/10.1080/10408398.2021.1929823DOI Listing
June 2021

Feed-forward activation of STAT3 signaling limits the efficacy of c-Met inhibitors in esophageal squamous cell carcinoma (ESCC) treatment.

Mol Carcinog 2021 07 21;60(7):481-496. Epub 2021 May 21.

Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital & Institute, Beijing, China.

c-Hepatocyte growth factor receptor (Met) inhibitors have demonstrated clinical benefits in some types of solid tumors. However, the efficacy of c-Met inhibitors in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we discovered that c-Met inhibitors induced "Signal Transducer and Activator of Transcription (STAT3)-addiction" in ESCC cells, and the feedback activation of STAT3 in ESCC cells limits the tumor response to c-Met inhibition. Mechanistically, c-Met inhibition increased the autocrine of several cytokines, including CCL2, interleukin 8, or leukemia inhibitory factor, and facilitated the interactions between the receptors of these cytokines and Janus Kinase1/2 (JAK1/2) to resultantly activate JAKs/STAT3 signaling. Pharmacological inhibition of c-Met together with cytokines/JAKs/STAT3 axis enhanced cancer cells regression in vitro. Importantly, combined c-Met and STAT3 inhibitors synergistically suppressed tumor growth and promoted the apoptosis of tumor cells without producing systematic toxicity. These findings suggest that inhibition of the STAT3 feedback loop may augment the response to c-Met inhibitors via the STAT3-mediated oncogene addiction in ESCC cells.
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http://dx.doi.org/10.1002/mc.23306DOI Listing
July 2021

Indole diketopiperazine alkaloids from the deep-sea-derived fungus sp. FS445.

Nat Prod Res 2021 May 12:1-9. Epub 2021 May 12.

State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangdong Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, China.

Twelve indole diketopiperazine alkaloids (‒) including four new ones aspechinulins A‒D (, , and ) were isolated from the deep-sea-derived fungus sp. FS445. Their structures were elucidated through spectroscopic analysis and the absolute configurations were determined by analyzing the experimental ECD data as well as the quantum chemical calculations. Compounds , and represented the first examples of indole diketopiperazine derivatives constructing a C unit at 11-NH through an imide linkage. The NO production inhibitory activity of the isolated compounds was evaluated and compounds ‒, and exhibited potential inhibitory activities against NO production with the IC values in the range of 20 ∼ 90 µM.
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http://dx.doi.org/10.1080/14786419.2021.1925271DOI Listing
May 2021

Nlp promotes autophagy through facilitating the interaction of Rab7 and FYCO1.

Signal Transduct Target Ther 2021 Apr 16;6(1):152. Epub 2021 Apr 16.

State Key Laboratory of Molecular Oncology, National Cancer center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Autophagy is the main degradation pathway to eliminate long-lived and aggregated proteins, aged or malfunctioning organelles, which is essential for the intracellular homeostasis and prevention of malignant transformation. Although the processes of autophagosome biogenesis have been well illuminated, the mechanism of autophagosome transport remains largely unclear. In this study, we demonstrated that the ninein-like protein (Nlp), a well-characterized centrosomal associated protein, was able to modulate autophagosome transport and facilitate autophagy. During autophagy, Nlp colocalized with autophagosomes and physically interacted with autophagosome marker LC3, autophagosome sorting protein Rab7 and its downstream effector FYCO1. Interestingly, Nlp enhanced the interaction between Rab7 and FYCO1, thus accelerated autophagic flux and the formation of autophagolysosomes. Furthermore, compared to the wild-type mice, NLP deficient mice treated with chemical agent DMBA were prone to increased incidence of hepatomegaly and liver cancer, which were tight associated with the hepatic autophagic defect. Taken together, our findings provide a new insight for the first time that the well-known centrosomal protein Nlp is also a new regulator of autophagy, which promotes the interaction of Rab7 and FYCO1 and facilitates the formation of autophagolysosome.
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http://dx.doi.org/10.1038/s41392-021-00543-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050283PMC
April 2021

Structural Tuning of a Flexible and Porous Polypyrrole Film by a Template-Assisted Method for Enhanced Capacitance for Supercapacitor Applications.

ACS Appl Mater Interfaces 2021 Apr 6;13(15):17726-17735. Epub 2021 Apr 6.

Shanghai Electrochemical Energy Devices Research Center, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Constructing a rational electrode structure for supercapacitors is critical to accelerate the electrochemical kinetics process and thus promote the capacitance. Focusing on the flexible supercapacitor electrode, we synthesized a three-dimensional (3D) porous polypyrrole (PPy) film using a modified vapor phase polymerization method with the use of a porous template (CaCO). The porous design provided the PPy film with an improved surface area and pore volume. The porous PPy film electrode was studied as a binder-free electrode for supercapacitors. It was found that the abundant interpenetrated pores created by the CaCO templates within the 3D framework are beneficial to overcoming the diffusion-controlled limit in the overall electrochemical process. It was revealed by electrochemical investigation that a more pseudocapacitive contribution than diffusion-controlled process contribution was observed in the total charge in the redox reaction. The galvanostatic charge/discharge (GCD) measurements showed that the optimized 3D porous PPy film electrode delivered a high capacitance of 313.6 F g and an areal capacitance of 98.0 mF cm at 1.0 A g in a three-electrode configuration, which is nearly three times that of the dense counterpart electrode synthesized in the absence of the CaCO template. A specific capacitance of 62.5 F g at 0.5 A g and 31.1 F g at 10 A g was obtained in a symmetric capacitor device. In addition, the porous structure provided the PPy film with the attractive capability of accommodating the volume change during the doping/dedoping process. This is essential for the PPy film to maintain a long cycling life in a practical operation for a supercapacitor. It turned out that a high capacitance retention up to 81.3% after 10,000 GCD cycles was obtained for the symmetric supercapacitor device with the 3D porous PPy electrode (57.1% capacitive retention was observed for the dense PPy electrode). The strategy and the insight analysis are expected to provide valuable guidance for the design and the synthesis of flexible and wearable film electrodes with high performance.
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http://dx.doi.org/10.1021/acsami.1c03553DOI Listing
April 2021

Endoluminal Motion Recognition of a Magnetically-Guided Capsule Endoscope Based on Capsule-Tissue Interaction Force.

Sensors (Basel) 2021 Mar 30;21(7). Epub 2021 Mar 30.

Beijing Advanced Innovation Center for Intelligent Robots and Systems, Beijing Institute of Technology, Beijing 100081, China.

A magnetically-guided capsule endoscope, embedding flexible force sensors, is designed to measure the capsule-tissue interaction force. The flexible force sensor is composed of eight force-sensitive elements surrounding the internal permanent magnet (IPM). The control of interaction force acting on the intestinal wall can reduce patient's discomfort and maintain the magnetic coupling between the external permanent magnet (EPM) and the IPM during capsule navigation. A flexible force sensor can achieve this control. In particular, by analyzing the signals of the force sensitive elements, we propose a method to recognize the status of the motion of the magnetic capsule, and provide corresponding formulas to evaluate whether the magnetic capsule follows the motion of the external driving magnet. Accuracy of the motion recognition in Ex Vivo tests reached 94% when the EPM was translated along the longitudinal axis. In addition, a method is proposed to realign the EPM and the IPM before the loss of their magnetic coupling. Its translational error, rotational error, and runtime are 7.04 ± 0.71 mm, 3.13 ± 0.47∘, and 11.4 ± 0.39 s, respectively. Finally, a control strategy is proposed to prevent the magnetic capsule endoscope from losing control during the magnetically-guided capsule colonoscopy.
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http://dx.doi.org/10.3390/s21072395DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036640PMC
March 2021

Food Safety in Post-COVID-19 Pandemic: Challenges and Countermeasures.

Biosensors (Basel) 2021 Mar 4;11(3). Epub 2021 Mar 4.

Key Laboratory of Food Nutrition and Functional Food of Hainan Province, College of Food Science and Engineering, Hainan University, Haikou 570228, China.

Understanding food safety hazard risks is essential to avoid potential negative heath impacts in the food supply chain in a post-COVID-19 pandemic era. Development of strategies for virus direction in foods plays an important role in food safety and verification. Early warning, tracing, and detection should be implemented as an integrated system in order to mitigate thecoronavirus disease 2019 (COVID-19) outbreak, in which the detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is critical as it not only concerns screening of populations but also monitoring of possible contaminated sources such as the food supply chain. In this review, we point out the consequences in different aspects of our daily life in the post-COVID-19 pandemic from the perspective of the food supply chain and the food industry. We summarize the possible transmission routes of COVID-19 in the food supply chain before exploring the development of corresponding detection tools of SARS-CoV-2. Accordingly, we compare different detection methods for the virus in foods, including different pretreatments of food matrices in the virus detection. Finally, the future perspectives are proposed.
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http://dx.doi.org/10.3390/bios11030071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000942PMC
March 2021

Bioactivity-guided isolation of immunomodulatory compounds from the fruits of Ligustrum lucidum.

J Ethnopharmacol 2021 Jun 30;274:114079. Epub 2021 Mar 30.

College of Veterinary Medicine, Northwest A&F University, 712100, Yangling, PR China. Electronic address:

Ethnopharmacological Relevance: The fruits of Ligustrum lucidum (FLL) W.T. Aiton (Oleaceae) is included in the 2020 "Chinese Pharmacopoeia" and is widely used in traditional Chinese medicine as a tonic. In recent years, FLL has been reported to improve immune function, but the bioactive compounds and mechanisms of FLL remain poorly characterized.

Aim Of The Study: To identify FFL compounds with strong immune activity and explore their molecular mechanisms.

Materials And Methods: The phagocytic activity of RAW264.7 macrophages and proliferation activity of spleen lymphocytes were used to guide the isolation of bioactive compounds from FLL extracts. Lymphocyte subpopulations, Ca concentrations, and surface molecule expression were analyzed using flow cytometry. Cytokine secretion was examined using ELISA. FITC-OVA uptake was observed using fluorescence microscopy. NF-κB activation was analyzed using western blotting.

Results: The extraction and isolation produced ten compounds, namely oleuropeinic acid, nuezhenide, isonuezhenide, salidroside, isoligustrosidic acid, ligulucidumosides A, 8(E)-nuezhenide, hydroxytyrosol, oleuropein, and p-hydroxyphenethyl 7-β-D-glucosideelenolic acid ester were isolated and identified from FLL-Bu-30%. Immunoactivity experiments showed that hydroxytyrosol had the strongest macrophage phagocytotic and lymphocyte proliferation-promoting activities. Further studies showed that hydroxytyrosol could significantly enhance lymphocyte subsets CD3, CD4/CD8, and CD3CD4CD8, promote IL-4, IFN-γ, and TNF-α secretion, and increase intracellular Ca concentrations. In addition, the results from RAW264.7 macrophages showed that hydroxytyrosol increased FITC-OVA uptake, induced TNF-α and IL-1β production, upregulated MHC-II, CD80, and CD86 expression, promoted cytoplasmic IκB-α degradation, and increased nuclear NF-κB p65 levels.

Conclusion: Our study provides substantial evidence regarding the mechanism of the immunomodulatory effects of compounds from FLL.
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http://dx.doi.org/10.1016/j.jep.2021.114079DOI Listing
June 2021

Downregulation of ITGA6 confers to the invasion of multiple myeloma and promotes progression to plasma cell leukaemia.

Br J Cancer 2021 May 30;124(11):1843-1853. Epub 2021 Mar 30.

Department of Cell Biology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou, China.

Background: Secondary plasma cell leukaemia (sPCL) is an aggressive form of multiple myeloma (MM), but the mechanism underlying MM progresses into PCL remains unknown.

Methods: Gene expression profiling of MM patients and PCL patients was analysed to identify the molecular differences between the two diseases. Cox survival regression and Kaplan-Meier analysis were performed to illustrate the impact of integrin subunit alpha 6 (ITGA6) on prognosis of MM. Invasion assays were performed to assess whether ITGA6 regulated the progression of MM to PCL.

Results: Gene expression profiling analyses showed that cell metastasis pathways were enriched in PCL and ITGA6 was differentially expressed between PCL and MM. ITGA6 expression was an independent prognostic factor for event-free survival (EFS) and overall survival (OS) of MM patients. Moreover, the stratification ability of the International Staging System (ISS) of MM was improved when including ITGA6 expression. Functional studies uncovered that increased ITGA6 reduced the myeloma cell invasion. Additionally, low expression of ITGA6 resulted from epigenetic downregulating of its anti-sense non-coding RNA, ITGA6-AS1.

Conclusion: Our data reveal that ITGA6 gradually decreases during plasma cell dyscrasias progression and low expression of ITGA6 contributes to myeloma metastasis. Moreover, ITGA6 abundance might help develop MM prognostic stratification.
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http://dx.doi.org/10.1038/s41416-021-01362-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144434PMC
May 2021

Long Noncoding RNA VESTAR Regulates Lymphangiogenesis and Lymph Node Metastasis of Esophageal Squamous Cell Carcinoma by Enhancing VEGFC mRNA Stability.

Cancer Res 2021 Jun 26;81(12):3187-3199. Epub 2021 Mar 26.

State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Lymph node metastasis is one of the most malignant clinical features in patients with esophageal squamous cell carcinoma (ESCC). Understanding the mechanism of lymph node metastasis will provide treatment strategies for patients with ESCC. Long noncoding RNAs (lncRNA) play a critical role in the development and progression of human cancers. However, the role and mechanism of lncRNAs in lymph node metastasis remain largely unknown. Here we show that mRNA stability-associated long noncoding RNA (VESTAR) is involved in lymph node metastasis of ESCC. VESTAR was overexpressed in ESCC tissues and was predictive of poor prognosis in patients with ESCC. In ESCC, NXF1 and SRSF3 facilitated nuclear export of VESTAR to the cytoplasm, which was associated with lymph node metastasis. Depletion of VESTAR inhibited ESCC-associated lymphangiogenesis and lymphatic metastasis. Mechanistically, VESTAR directly bound and stabilized mRNA. VESTAR also interacted with HuR, a positive regulator of mRNA stability, and increased HuR binding to mRNA. Our study reveals a novel lncRNA-guided mechanism of lymph node metastasis in ESCC and may provide a potential target for treatment of ESCC lymphatic metastasis. SIGNIFICANCE: These findings illustrate the lncRNA-guided regulation of mRNA stability via direct RNA-RNA interactions, highlighting a therapeutic target for patients with ESCC with lymphatic metastasis.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-1713DOI Listing
June 2021

An experimental study on the use of a sequencing-batch membrane bioreactor (SBMBR) for the treatment of mixed municipal wastewater.

Water Sci Technol 2021 Mar;83(6):1459-1469

China Metallurgical Group Corporation Lu 'an Water co. LTD, Lu'an, Anhui 237000, China.

Several water treatment techniques have been combined using the sequencing batch reactor with the membrane bioreactor for addressing water pollution. However, cleaning of the membrane is dependent on the approach involved as well as the operating conditions. In the present study, the sequencing-batch membrane bioreactor was used to treat real mixed municipal wastewater. The pollutant removal and membrane filtration performances were examined. The results show that the average removal rates of chemical oxygen demand (COD), total nitrogen, NH-N, total phosphorus, and turbidity were 90.75, 63.52, 92.85, 87.58, and 99.48%, respectively, when the system was in continuous operation for 95 days. The membrane had a significant effect on COD and turbidity removal and provided stable performances for nitrogen and phosphorus removal. By observing the appearance of the membrane modules before and after the cleaning operation, it was concluded that the deposited sludge and granular sediment on the membrane surface can be effectively removed by hydraulic cleaning. In addition, recovery of membrane filtration performance to 60% of that of a new membrane can be achieved. Furthermore, we found that different sequences and duration of cleaning have different effects on the recovery of membrane filtration performance.
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http://dx.doi.org/10.2166/wst.2021.064DOI Listing
March 2021

Extracellular vesicles derived from oesophageal cancer containing P4HB promote muscle wasting via regulating PHGDH/Bcl-2/caspase-3 pathway.

J Extracell Vesicles 2021 03 10;10(5):e12060. Epub 2021 Mar 10.

State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China.

Cachexia, characterized by loss of skeletal muscle mass and function, is estimated to inflict the majority of patients with oesophageal squamous cell carcinoma (ESCC) and associated with their poor prognosis. However, its underlying mechanisms remain elusive. Here, we developed an ESCC-induced cachexia mouse model using human xenograft ESCC cell lines and found that ESCC-derived extracellular vesicles (EVs) containing prolyl 4-hydroxylase subunit beta (P4HB) induced apoptosis of skeletal muscle cells. We further identified that P4HB promoted apoptotic response through activating ubiquitin-dependent proteolytic pathway and regulated the stability of phosphoglycerate dehydrogenase (PHGDH) and subsequent antiapoptotic protein Bcl-2. Additionally, we proved that the P4HB inhibitor, CCF642, not only rescued apoptosis of muscle cells in vitro, but also prevented body weight loss and muscle wasting in ESCC-induced cachexia mouse model. Overall, these findings demonstrate a novel pathway for ESCC-induced muscle wasting and advocate for the development of P4HB as a potential intervention target for cachexia in patients with ESCC.
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http://dx.doi.org/10.1002/jev2.12060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944388PMC
March 2021

Pheochromocytoma-related cardiomyopathy presenting as acute myocardial infarction: A case report.

Medicine (Baltimore) 2021 Mar;100(11):e24984

Intensive Care Unit, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou.

Introduction: Pheochromocytoma (PHEO)-related cardiomyopathy is a rare condition in which release of a large amount of catecholamines leads to severe vasoconstriction, coronary vasospasm, myocardial ischemia, injury, and necrosis. Its clinical manifestations can be similar to those of acute coronary syndrome.

Patient Concerns: A 63-year-old woman was diagnosed with acute non-ST segment elevation myocardial infarction following chest pain for 8 hours. The results of coronary angiography were normal. The patient developed dyspnea, cough with frothy pink sputum, paroxysmal sweating, arrhythmia, and blood pressure fluctuation, and was transferred to the intensive care unit for monitoring and treatment.

Diagnosis: PHEO, catecholamine cardiomyopathy (CICMP).

Intervention: After monitoring the pulse index continuous cardiac output and treatment with α and β adrenergic receptor blockers for 18 days, laparoscopic resection of the left adrenal mass was performed.

Outcomes: The patient's condition improved and she was discharged 31 days after admission. Outpatient follow-up examinations 1 month and 1 year later did not show recurrence.

Lessons: PHEO can cause CICMP, the manifestations of which are partly similar to those of takotsubo cardiomyopathy (TTC). Once the patient's condition stabilizes, surgery should be considered. Fluid management is necessary, and agents such as α and β adrenergic receptor blockers should be administered.
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http://dx.doi.org/10.1097/MD.0000000000024984DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982151PMC
March 2021

Docetaxel maintenance therapy versus best supportive care after first-line chemotherapy with different dose docetaxel plus cisplatin for advanced non-small cell lung cancer (TFINE study, CTONG-0904): an open-label, randomized, phase III trial.

Ann Transl Med 2021 Feb;9(4):338

Sanofi (China) Investment Co., Ltd. Shanghai Branch, Shanghai, China.

Background: Maintenance therapy is important in the management of advanced non-small cell lung cancer (NSCLC). The present TFINE study assessed the efficacy and safety of docetaxel continuation maintenance (DCM) therapy after first-line treatment with different doses of docetaxel plus cisplatin.

Methods: In this open-label, randomized, phase III study, newly diagnosed patients with advanced NSCLC were initially randomized (R1, 1:1) to receive first-line treatment with cisplatin 75 mg/m plus docetaxel 75 mg/m (DC75) or 60 mg/m (DC60) for up to 4 cycles. Patients without progression were further randomized (R2, 1:2) to best supportive care (BSC) or DCM (60 mg/m) for up to 6 cycles. The primary endpoint was progression-free survival (PFS) after R2, and the secondary endpoints included best response rate in first-line treatment, overall survival (OS), time to progression (TTP), and toxicities.

Results: A total of 375 patients were enrolled in R1 and 184 of these patients continued in R2. DCM significantly prolonged PFS compared to BSC (HR =0.57, median PFS =5.8 . 3.0 months, P=0.002). The response rates were 30.2% and 23.9% in the DC75 and DC60 groups, respectively (P=0.17). There was no significant difference in OS (12.3 . 13.7 months, P=0.77). Additionally, 47.8% and 45.7% of patients reported AEs in the DC75 and DC60 groups, respectively. Diarrhea was more frequent with DC75 than with DC60 (8.6% . 3.2%, P=0.029). Other toxicities were comparable between the 2 docetaxel dose groups.

Conclusions: Continuation maintenance treatment with docetaxel is well tolerated and improves PFS in patients with NSCLC. The docetaxel dose of 60 mg/m may be preferred due to similar efficacy and less diarrhea.

Trial Registration: NCT01038661.
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http://dx.doi.org/10.21037/atm-20-8078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944306PMC
February 2021
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