Publications by authors named "Jingjing Zhang"

1,127 Publications

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Fabrication of microcapsules with core-shell structure for oral delivery of dual drugs and real-time computed tomography imaging.

IET Nanobiotechnol 2021 Sep 15;15(7):619-626. Epub 2021 May 15.

Zhangjiagang Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Zhangjiagang, Jiangsu, China.

Although multidrug combinations are an effective therapeutic strategy for serious disease in clinical practice, their therapeutic effect may be reduced because they conflict with each other medicinally in certain cases. Hence, there is an urgent need to develop a single drug carrier for precise multidrug delivery to avoid this interference. A reverse coordination method is reported that fabricates a double-layer barium sulphate microcapsule ([email protected] MS) for two drugs separately loading simultaneously. In addition, BS nanoclusters were synthesised in situ inside the [email protected] MSs for real-time computed tomography (CT) imaging. The results showed that the [email protected] MSs with a particle size of approximately 2 mm exhibited a uniform sphere. Because BS nanoclusters have a high X-ray attenuation coefficient, the retention of [email protected] MSs in the digestive tract could be monitored through CT imaging in real time. More important, the core-shell structure of [email protected] MSs encapsulating two different drugs could be released in spatiotemporal order in an acidic stomach environment. The as-synthesis [email protected] MSs with a core-shell structure and real-time imaging performance provide an ideal carrier for the oral administration of multiple drugs simultaneously loaded but sequentially released.
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http://dx.doi.org/10.1049/nbt2.12058DOI Listing
September 2021

Dyspnea Measurement in Acute Heart Failure: A Systematic Review and Evidence Map of Randomized Controlled Trials.

Front Med (Lausanne) 2021 6;8:728772. Epub 2021 Oct 6.

Key Laboratory of Chinese Internal Medicine of Ministry of Education, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.

Dyspnea is the most common presenting symptom among patients hospitalized for acute heart failure (AHF). Dyspnea relief constitutes a clinically relevant therapeutic target and endpoint for clinical trials and regulatory approval. However, there have been no widely accepted dyspnea measurement standards in AHF. By systematic review and mapping the current evidence of the applied scales, timing, and results of measurement, we hope to provide some new insights and recommendations for dyspnea measurement. PubMed, Embase, Cochrane Library, and Web of Science were searched from inception until August 27, 2020. Randomized controlled trials (RCTs) with dyspnea severity measured as the endpoint in patients with AHF were included. Out of a total of 63 studies, 28 had dyspnea as the primary endpoint. The Likert scale (34, 54%) and visual analog scale (VAS) (22, 35%) were most widely used for dyspnea assessment. Among the 43 studies with detailed results, dyspnea was assessed most frequently on days 1, 2, 3, and 6 h after randomization or drug administration. Compared with control groups, better dyspnea relief was observed in the experimental groups in 21 studies. Only four studies that assessed tolvaptan compared with control on the proportion of dyspnea improvement met the criteria for meta-analyses, which did not indicate beneficial effect of dyspnea improvement on day 1 (RR: 1.16; 95% CI: 0.99-1.37; = 0.07; = 61%). The applied scales, analytical approaches, and timing of measurement are in diversity, which has impeded the comprehensive evaluation of clinical efficacy of potential therapies managing dyspnea in patients with AHF. Developing a more general measurement tool established on the unified unidimensional scales, standardized operation protocol to record the continuation, and clinically significant difference of dyspnea variation may be a promising approach. In addition, to evaluate the effect of experimental therapies on dyspnea more precisely, the screening time and blinded assessment are factors that need to be considered.
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http://dx.doi.org/10.3389/fmed.2021.728772DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526558PMC
October 2021

Active digital spoof plasmonics.

Natl Sci Rev 2020 Feb 4;7(2):261-269. Epub 2019 Oct 4.

State Key Laboratory of Millimeter Waves, Southeast University, Nanjing 210096, China.

Digital coding and digital modulation are the foundation of modern information science. The combination of digital technology with metamaterials provides a powerful scheme for spatial and temporal controls of electromagnetic waves. Such a technique, however, has thus far been limited to the control of free-space light. Its application to plasmonics to shape subwavelength fields still remains elusive. Here, we report the design and experimental realization of a tunable conformal plasmonic metasurface, which is capable of digitally coding and modulating designer surface plasmons at the deep-subwavelength scale. Based on dynamical switching between two discrete dispersion states in a controlled manner, we achieve digital modulations of both amplitude and phase of surface waves with nearly 100% modulation depth on a single device. Our study not only introduces a new approach for active dispersion engineering, but also constitutes an important step towards the realization of subwavelength integrated plasmonic circuits.
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http://dx.doi.org/10.1093/nsr/nwz148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288847PMC
February 2020

High-resolution mapping of brain vasculature and its impairment in the hippocampus of Alzheimer's disease mice.

Natl Sci Rev 2019 Nov 28;6(6):1223-1238. Epub 2019 Aug 28.

School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.

Accumulating evidence indicates the critical importance of cerebrovascular dysfunction in the pathogenesis of Alzheimer's disease (AD). However, systematic comparative studies on the precise brain vasculature of wild-type and AD model mice are still rare. Using an image-optimization method for analysing Micro-Optical Sectioning Tomography (MOST) data, we generated cross-scale whole-brain 3D atlases that cover the entire vascular system from large vessels down to smallest capillaries at submicron resolution, for both wild-type mice and a transgenic (APP/PS1) mouse model of AD. In addition to distinct vascular patterns in different brain regions, we found that the main vessels of the molecular layer of the hippocampal dentate gyrus (DG-ml) undergo abrupt changes in both diameter and branch angle, spreading a unique comb-like pattern of capillaries. By using a quantitative analysis workflow, we identified in the hippocampus of AD mice an overall reduction of the mean vascular diameter, volume fraction and branch angle, with most significant impairment in the DG-ml. In addition, virtual endoscopy revealed irregular morphological features in the vessel lumen of the AD mice, potentially contributing to the impairment of blood flow. Our results demonstrate the capability of high-resolution cross-scale evaluation of brain vasculature and underscore the importance of studying hippocampal microcirculation for understanding AD pathogenesis.
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http://dx.doi.org/10.1093/nsr/nwz124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291402PMC
November 2019

Recent progress in reactivity study and synthetic application of N-heterocyclic phosphorus hydrides.

Natl Sci Rev 2021 Apr 30;8(4):nwaa253. Epub 2020 Sep 30.

Center of Basic Molecular Science, Department of Chemistry, Tsinghua University, Beijing 100084, China.

N-heterocyclic phosphines (NHPs) have recently emerged as a new group of promising catalysts for metal-free reductions, owing to their unique hydridic reactivity. The excellent hydricity of NHPs, which rivals or even exceeds those of many metal-based hydrides, is the result of hyperconjugative interactions between the lone-pair electrons on N atoms and the adjacent σ(P-H) orbital. Compared with the conventional protic reactivity of phosphines, this umpolung P-H reactivity leads to hydridic selectivity in NHP-mediated reductions. This reactivity has therefore found many applications in the catalytic reduction of polar unsaturated bonds and in the hydroboration of pyridines. This review summarizes recent progress in studies of the reactivity and synthetic applications of these phosphorus-based hydrides, with the aim of providing practical information to enable exploitation of their synthetically useful chemistry.
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http://dx.doi.org/10.1093/nsr/nwaa253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288402PMC
April 2021

TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos.

Stem Cell Reports 2021 Oct 4. Epub 2021 Oct 4.

Institute of Stem Cell and Regenerative Biology, College of Animal Science and Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction (Huazhong Agricultural University), Ministry of Education, Wuhan 430070, China; The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, China; Hubei Hongshan Laboratory, Wuhan 430070, China. Electronic address:

Pig cloning by somatic cell nuclear transfer (SCNT) frequently undergoes incomplete epigenetic remodeling during the maternal-to-zygotic transition, which leads to a significant embryonic loss before implantation. Here, we generated the first genome-wide landscapes of histone methylation in pig SCNT embryos. Excessive H3K9me3 and H3K27me3, but not H3K4me3, were observed in the genomic regions with unfaithful embryonic genome activation and donor-cell-specific gene silencing. A combination of H3K9 demethylase KDM4A and GSK126, an inhibitor of H3K27me3 writer, were able to remove these epigenetic barriers and restore the global transcriptome in SCNT embryos. More importantly, thymine DNA glycosylase (TDG) was defined as a pig-specific epigenetic regulator for nuclear reprogramming, which was not reactivated by H3K9me3 and H3K27me3 removal. Both combined treatment and transient TDG overexpression promoted DNA demethylation and enhanced the blastocyst-forming rates of SCNT embryos, thus offering valuable methods to increase the cloning efficiency of genome-edited pigs for agricultural and biomedical purposes.
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http://dx.doi.org/10.1016/j.stemcr.2021.09.012DOI Listing
October 2021

Active Spoof Plasmonics: from Design to Applications.

J Phys Condens Matter 2021 Oct 21. Epub 2021 Oct 21.

Department of Radio Engineering, Southeast University, Center for Computational Electromagnetics, Nanjing 210096, PEOPLES REPUBLIC OF CHINA, Nanjing, 210096, CHINA.

Spoof plasmonic metamaterials enable the transmission of electromagnetic energies with strong field confinement, opening new pathways to the miniaturization of devices for modern communications. The design of active, reconfigurable, and nonlinear devices for the efficient generation and guidance, dynamic modulation, and accurate detection of spoof surface plasmonic signals has become one of the major research directions in the field of spoof plasmonic metamaterials. In this article, we review recent progress in the studies on spoof surface plasmons with a special focus on the active spoof surface plasmonic devices and systems. Different design schemes are introduced, and the related applications including reconfigurable filters, high-resolution sensors for chemical and biological sensing, graphene-based attenuators, programmable and multi-functional devices, nonlinear devices, splitters, leaky-wave antennas and multi-scheme digital modulators are discussed. The presence of active SSPPs based on different design schemes makes it possible to dynamically control electromagnetic waves in real time. The promising future of active spoof plasmonic metamaterials in the communication systems is also speculated.
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http://dx.doi.org/10.1088/1361-648X/ac31f7DOI Listing
October 2021

A Bio-inspired Extended-Gate Metal-Oxide-Semiconductor Field-Effect-Transistor for Highly Sensitive Amino Acid Enantiodiscrimination.

Anal Chem 2021 Oct 21. Epub 2021 Oct 21.

Tianjin Key Laboratory of Molecular Optoelectronic Science, Department of Chemistry, School of Science, Tianjin University, Tianjin 300354, P. R. China.

As the most important small molecules revealing the origins of life, amino acids (AAs) play essential roles in living organisms and their facile enantiodiscrimination has long been a great challenge for analytical chemists. Inspired by the specific stereomatching effect between biomolecules and AA enantiomers, herein, we first developed a bio-inspired highly sensitive platform based on an extended-gate metal-oxide-semiconductor field-effect-transistor (EG-MOSFET) for highly sensitive AA enantiodiscrimination. Bovine serum albumin (BSA) was self-assembled on deposited Au surfaces to afford the extended gate (EG) sensing unit, and its enantiorecognition ability was initially verified using common electrochemical techniques. The EG was thereafter installed to a MOSFET to build the desired BSA-EG-MOSFET highly sensitive chiral sensing platform, which realized the efficient enantiodiscrimination of essential AAs with high sensitivity, where effective chiral resolution was achieved at the femtomole level to phenylalanine (Phe). Combining molecular docking and circular dichroism spectroscopy, the weak intermolecular interactions between BSA and AAs enantiomers were investigated and the mechanism for signal amplification was proposed. Our results demonstrate that the as-fabricated biosensor has great potential in highly sensitive chiral sensing fields and can also afford a potential tool for biomolecular interaction investigations.
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http://dx.doi.org/10.1021/acs.analchem.1c02460DOI Listing
October 2021

Somatostatin receptor imaging with [Ga]Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) in patients with nasopharyngeal carcinoma.

Eur J Nucl Med Mol Imaging 2021 Oct 19. Epub 2021 Oct 19.

Department of Nuclear Medicine & Minnan PET Center, The First Affiliated Hospital of Xiamen University, Xiamen, China.

Purpose: To explore the feasibility of [Ga]Ga-DOTATATE positron emission tomography/computed tomography (PET/CT) in patients with non-keratinizing nasopharyngeal carcinoma (NPC) and to evaluate whether [Ga]Ga-DOTATATE PET/CT could be used for non-invasive determination of somatostatin receptor 2 (SSTR2) expression in NPC.

Methods: This prospective study included patients with NPC who underwent [Ga]Ga-DOTATATE PET/CT between February and May 2021. The [Ga]Ga-DOTATATE and [F]FDG uptakes in primary and metastatic NPC lesions were calculated and compared, and the [Ga]Ga-DOTATATE uptake between SSTR2 score groups was analysed.

Results: A total of 36 participants (25 patients, initial staging; 11 patients, recurrence detection) were included; 33 patients also underwent [F]FDG PET/CT for staging/restaging as a part of their routine diagnostic workup. [Ga]Ga-DOTATATE PET/CT showed an intense tracer uptake in primary and metastatic NPC lesions. The radiotracer uptake was higher with [Ga]Ga-DOTATATE than with [F]FDG PET in primary NPC lesions (SUVmax: 12.03 vs. 10.07, P = 0.048; tumour-to-brain ratio: 36.16 vs. 0.86, P < 0.001) and regional lymph node metastases (median SUVmax: 9.11 vs. 6.12, P < 0.001) and comparable in bone and visceral metastases. Importantly, most NPC lesions showed intense SSTR2 expression (85.7%), which was strongly correlated with the [Ga]Ga-DOTATATE uptake. The SUVmax of SSTR2-negative lesions was significantly lower than that of SSTR2-positive lesions (SUVmax: 4.95 vs. 12.61, P = 0.013).

Conclusion: [Ga]Ga-DOTATATE PET/CT is a promising imaging modality for detecting primary and metastatic NPC, with favourable image contrast and comparable diagnostic efficacy when compared to [F]FDG PET/CT. An intense SSTR2 expression was observed in most NPCs, and this expression was significantly correlated with the [Ga]Ga-DOTATATE uptake.
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http://dx.doi.org/10.1007/s00259-021-05587-7DOI Listing
October 2021

Hormetic effects of zinc on growth and antioxidant defense system of wheat plants.

Sci Total Environ 2021 Oct 15:150992. Epub 2021 Oct 15.

College of Resources and Environment, Henan Agricultural University, Zhengzhou 450002, PR China. Electronic address:

Although hormesis induced by heavy metals is a well-known phenomenon, the involved biological mechanisms are not fully understood. Zinc (Zn) is an essential micronutrient for wheat, an important crop contributing to food security as a main staple food; however, excessive Zn is detrimental to the growth of wheat. The aim of this study was to evaluate morphological and physiological responses of two wheat varieties exposed to a broad range of Zn concentrations (0-1000 μM) for 14 days. Hormesis was induced by Zn in both wheat varieties. Treatment with 10-100 μM Zn promoted biomass accumulation by enhancing the photosynthetic ability, the chlorophyll content and the activities of antioxidant enzymes. Increased root/shoot ratio suggested that shoot growth was severely inhibited when Zn concentration exceeded 300 μM by reducing photosynthetic ability and the content of photosynthetic pigments. Excessive Zn accumulation (Zn treatment of 300-1000 μM) in leaf and root induced membrane injuries through lipid peroxidation as malondialdehyde (MDA) content increased with increasing Zn concentration. The results show that MDA content was higher than other treatments by 16.1-151.1% and 15.0-88.3% (XN979) and 36.8-235.7% and 20.6-83.8% (BN207) in the leaves and roots under 1000 μM Zn treatment. To defend against Zn toxicity, ascorbate (AsA), glutathione (GSH), non-protein thiols (NPT) and phytochelatin (PC) content of both wheat varieties (except leaf GSH content of BN207) was increased, while, the activities of superoxide dismutase, peroxidase, catalase, ascorbate peroxidase, and the content of soluble protein decreased by 300-1000 μM Zn. The results showed that AsA-GSH cycle and NPT and PC content of wheat seedlings play important roles in defending against Zn toxicity. This study contributes new insights into the physiological mechanisms underlying the hormetic response of wheat to Zn, which could be beneficial for optimizing plant health in changing environments and improving risk assessments.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150992DOI Listing
October 2021

A capillary electrophoresis-based variant hotspot genotyping method for rapid and reliable analysis of the phenylalanine hydroxylase gene in the Chinese Han population.

Clin Chim Acta 2021 Oct 12;523:267-272. Epub 2021 Oct 12.

Department of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu 210004, People's Republic of China. Electronic address:

Background And Aims: Hyperphenylalaninemia (HPA) is a common autosomal recessive disorder of phenylalanine metabolism, mainly caused by the deficiency of phenylalanine hydroxylase gene (PAH). A simple, fast, and accurate assay to achieve early diagnosis for children with HPA is required.

Materials And Methods: In the present study, we established a SNaPshot-based assay that allows the simultaneous genotyping of 96 hotspot variants in the PAH gene. First, 18 Chinese HPA patients were analyzed by next generation sequencing (NGS) and SNaPshot in parallel. Then, the SNaPshot assay was performed to analyze the mutational spectrum of the PAH in 4,276 individuals in Eastern China.

Results: A total of 36 variants in the PAH gene were successfully identified by NGS, while the SNaPshot assay identified 34 PAH variants in these patients. Thus, the SNaPshot assay achieved the sensitivity and specificity of 91.6% and 100.0%, respectively. Furthermore, the carrier rate was approximately 1 in 58 (1.73%) in 4,276 individuals, and c.728G > A was the most common variant.

Conclusion: In summary, SNaPshot can accurately and rapidly detect PAH gene variants at a comparable performance and lower cost as compared with NGS. Our results suggest that SNaPshot may serve as a promising approach for a routine genetic test in clinical practice.
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http://dx.doi.org/10.1016/j.cca.2021.10.009DOI Listing
October 2021

SERPINE2/PN-1 regulates the DNA damage response and radioresistance by activating ATM in lung cancer.

Cancer Lett 2021 Oct 11. Epub 2021 Oct 11.

Department of Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang Chinese Medical University, Hangzhou, 310006, China; Department of Oncology, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China. Electronic address:

Although the DNA damage response (DDR) is associated with the radioresistance characteristics of lung cancer cells, the specific regulators and underlying mechanisms of the DDR are unclear. Here, we identified the serine proteinase inhibitor clade E member 2 (SERPINE2) as a modulator of radiosensitivity and the DDR in lung cancer. Cells exhibiting radioresistance after ionizing radiation show upregulation of SERPINE2, and SERPINE2 knockdown improves tumor radiosensitivity in vitro and in vivo. Functionally, SERPINE2 deficiency causes a reduction in homologous recombination repair, rapid recovery of cell cycle checkpoints, and suppression of migration and invasion. Mechanistically, SERPINE2 knockdown inhibits the accumulation of p-ATM and the downstream repair protein RAD51 during DNA repair, and RAD51 can restore DNA damage and radioresistance phenotypes in lung cancer cells. Furthermore, SERPINE2 can directly interact with MRE11 and ATM to facilitate its phosphorylation in HR-mediated DSB repair. In addition, high SERPINE2 expression correlates with dismal prognosis in lung adenocarcinoma patients, and a high serum SERPINE2 concentration predicts a poor response to radiotherapy in non-small cell lung cancer patients. In summary, these findings indicate a novel regulatory mechanism by which SERPINE2 modulates the DDR and radioresistance in lung cancer.
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http://dx.doi.org/10.1016/j.canlet.2021.10.001DOI Listing
October 2021

Investigation of the Release Mechanism and Mould Resistance of Citral-Loaded Bamboo Strips.

Polymers (Basel) 2021 Sep 28;13(19). Epub 2021 Sep 28.

College of Chemistry and Materials Engineering, Zhejiang A & F University, Hangzhou 311300, China.

In the present study, the sustained-release system loading citral was synthesised by using PNIPAm nanohydrogel as a carrier and analysed its drug-release kinetics and mechanism. Four release models, namely zero-order, first-order, Higuchi, and Peppas, were employed to fit the experimental data, and the underlying action mechanism was analysed. The optimised system was applied to treat a bamboo mould, followed by assessment of the mould-proof performance. Our experimental results revealed that the release kinetics equation of the system conformed to the first order; the higher the external temperature, the better the match was. In the release process, PNIPAm demonstrated a good protection and sustained-release effect on citral. Under the pressure of 0.5 MPa, immersion time of 120 min, and the system concentration ratio of 1, the optimal drug-loading parameters were obtained using the slow-release system with the best release parameters. Compared to the other conditions, bamboos treated with pressure impregnation demonstrated a better control effect on bamboo mould, while the control effect on , , , and mixed mould was 100% after 28 days. Moreover, the structure and colour of bamboo remained unchanged during the entire process of mould control.
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http://dx.doi.org/10.3390/polym13193314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512208PMC
September 2021

BRCA2 in mammalian meiosis.

Trends Cell Biol 2021 Oct 5. Epub 2021 Oct 5.

Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg SE-40530, Sweden. Electronic address:

Breast cancer type 2 susceptibility protein (BRCA2) is a central regulator of homologous recombination in somatic cells and safeguards genomic integrity against DNA double-strand breaks (DSBs). Recent evidence suggests that association with unique meiosis-specific cofactors allows BRCA2 to facilitate homologous recombination in germ cells.
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http://dx.doi.org/10.1016/j.tcb.2021.09.003DOI Listing
October 2021

mmBCFA C17iso ensures endoplasmic reticulum integrity for lipid droplet growth.

J Cell Biol 2021 Nov 8;220(11). Epub 2021 Oct 8.

Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, Yunnan, China.

In eukaryote cells, lipid droplets (LDs) are key intracellular organelles that dynamically regulate cellular energy homeostasis. LDs originate from the ER and continuously contact the ER during their growth. How the ER affects LD growth is largely unknown. Here, we show that RNAi knockdown of acs-1, encoding an acyl-CoA synthetase required for the biosynthesis of monomethyl branched-chain fatty acids C15iso and C17iso, remarkably prevented LD growth in Caenorhabditis elegans. Dietary C17iso, or complex lipids with C17iso including phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol, could fully restore the LD growth in the acs-1RNAi worms. Mechanistically, C17iso may incorporate into phospholipids to ensure the membrane integrity of the ER so as to maintain the function of ER-resident enzymes such as SCD/stearoyl-CoA desaturase and DGAT2/diacylglycerol acyltransferase for appropriate lipid synthesis and LD growth. Collectively, our work uncovers a unique fatty acid, C17iso, as the side chain of phospholipids for determining the ER homeostasis for LD growth in an intact organism, C. elegans.
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http://dx.doi.org/10.1083/jcb.202102122DOI Listing
November 2021

IL-13 Derived Type 2 Innate Lymphocytes Ameliorates Cardiomyocyte Apoptosis Through STAT3 Signaling Pathway.

Front Cell Dev Biol 2021 20;9:742662. Epub 2021 Sep 20.

Department of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

The involvement of cardiomyopathy during sepsis means higher mortality and prolonged length of hospital stay. Many efforts have been made to alleviate the apoptosis of cardiomyocytes in sepsis. The huge potential of IL-13 in tissue repair has attracted increasing attention. In the present study, we used LPS-treated mice or primary cardiomyocytes as a sepsis model to explore the anti-apoptotic ability of IL-13. It was found that an increased level of exogenous IL-13 was beneficial to the recovery of heart function in sepsis, and this anti-apoptotic effect of IL-13 was probably through enhancing the phosphorylation of STAT3 Ser727. In addition, we identified that the heart protective effect of IL-13 was associated with type 2 innate lymphocytes (ILC2). All these findings may provide a potential promising treatment for sepsis-induced cardiomyopathy.
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http://dx.doi.org/10.3389/fcell.2021.742662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488199PMC
September 2021

Quantification of HER2 in COS7 cells using quantum weak measurement.

Opt Express 2021 Sep;29(19):30337-30347

A Mach-Zehnder interferometer system based on weak measurement was set up to determinate the concentration variation of molecule by measuring the phase difference change between the two optical paths. The spectrum of the light was recorded to monitor the concentration of trastuzumab (Herceptin), which is a humanised monoclonal antibody, targeted to human epidermal growth factor receptor 2 (HER2). The trastuzumab targeting to HER2 was real-time detected and continuously monitored, the HER2 numbers of COS7 cells on a coverslip was determined at pico-molar level. Our weak measurement enabled method proposes an alternative approach for the concentration detection of molecules, providing a promising functional tool for the quantification of HER2 in cancer cells, possibly promoting fields such as the diagnosis and treatment of cancer.
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http://dx.doi.org/10.1364/OE.437400DOI Listing
September 2021

Astrocytic YAP prevents the demyelination through promoting expression of cholesterol synthesis genes in experimental autoimmune encephalomyelitis.

Cell Death Dis 2021 Oct 5;12(10):907. Epub 2021 Oct 5.

School of Pharmacy, and Department of Neurosurgery of the Affiliated Hospital, Hangzhou Normal University, Hangzhou, Zhejiang, China.

Cholesterols are the main components of myelin, and are mainly synthesized in astrocytes and transported to oligodendrocytes and neurons in the adult brain. It has been reported that Hippo/yes-associated protein (YAP) pathways are involved in cholesterol synthesis in the liver, however, it remains unknown whether YAP signaling can prevent the demyelination through promoting cholesterol synthesis in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of multiple sclerosis characterized by neuroinflammation and demyelination. Here, we found that YAP was upregulated and activated in astrocytes of spinal cords of EAE mice through suppression of the Hippo pathway. YAP deletion in astrocytes aggravated EAE with earlier onset, severer inflammatory infiltration, demyelination, and more loss of neurons. Furthermore, we found that the neuroinflammation was aggravated and the proliferation of astrocytes was decreased in YAP-CKO EAE mice. Mechanically, RNA-seq revealed that the expression of cholesterol-synthesis pathway genes such as HMGCS1 were decreased in YAP astrocytes. qPCR, western blot, and immunostaining further confirmed the more significant reduction of HMGCS1 in spinal cord astrocytes of YAP-CKO EAE mice. Interestingly, upregulation of cholesterol-synthesis pathways by diarylpropionitrile (DPN) (an ERβ-ligand, to upregulate the expression of HMGCS1) treatment partially rescued the demyelination deficits in YAP-CKO EAE mice. Finally, activation of YAP by XMU-MP-1 treatment promoted the expression of HMGCS1 in astrocytes and partially rescued the demyelination and inflammatory infiltration deficits in EAE mice. These findings identify unrecognized functions of astrocytic YAP in the prevention of demyelination through promoting cholesterol synthesis in EAE, and reveal a novel pathway of YAP/HMGCS1 for cholesterol synthesis in EAE pathology.
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http://dx.doi.org/10.1038/s41419-021-04203-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8492624PMC
October 2021

Genome mining of novel rubiginones from Streptomyces sp. CB02414 and characterization of the post-PKS modification steps in rubiginone biosynthesis.

Microb Cell Fact 2021 Oct 2;20(1):192. Epub 2021 Oct 2.

Xiangya International Academy of Translational Medicine, Central South University, Tongzipo Road, #172, Yuelu District, Changsha, 410013, Hunan, China.

Background: Rubiginones belong to the angucycline family of aromatic polyketides, and they have been shown to potentiate the vincristine (VCR)-induced cytotoxicity against VCR-resistant cancer cell lines. However, the biosynthetic gene clusters (BGCs) and biosynthetic pathways for rubiginones have not been reported yet.

Results: In this study, based on bioinformatics analysis of the genome of Streptomyces sp. CB02414, we predicted the functions of the two type II polyketide synthases (PKSs) BGCs. The rub gene cluster was predicted to encode metabolites of the angucycline family. Scale-up fermentation of the CB02414 wild-type strain led to the discovery of eight rubiginones, including five new ones (rubiginones J, K, L, M, and N). Rubiginone J was proposed to be the final product of the rub gene cluster, which features extensive oxidation on the A-ring of the angucycline skeleton. Based on the production profiles of the CB02414 wild-type and the mutant strains, we proposed a biosynthetic pathway for the rubiginones in CB02414.

Conclusions: A genome mining strategy enabled the efficient discovery of new rubiginones from Streptomyces sp. CB02414. Based on the isolated biosynthetic intermediates, a plausible biosynthetic pathway for the rubiginones was proposed. Our research lays the foundation for further studies on the mechanism of the cytochrome P450-catalyzed oxidation of angucyclines and for the generation of novel angucyclines using combinatorial biosynthesis strategies.
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http://dx.doi.org/10.1186/s12934-021-01681-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487521PMC
October 2021

Insight into the activation mechanisms of biochar by boric acid and its application for the removal of sulfamethoxazole.

J Hazard Mater 2021 Sep 24;424(Pt A):127333. Epub 2021 Sep 24.

School of Civil Engineering, Beijing International Scientific and Technological Cooperation Base of Water Pollution Control Techniques for Antibiotics and Resistance genes, Beijing Jiaotong University, 3 Shangyuancun, Beijing 100044, China. Electronic address:

Sulfamethoxazole (SMX) is frequently detected in the environment and causes a huge threaten to human health. Biochar (BC) is a metal-free adsorbent and generally exhibits a good adsorption capacity for SMX. However, the current activated methods usually result in the high energy consumption and low yield of the biochar. In this study, biochar was activated by boric acid under limited oxygen condition. The yield of biochar was increased by 103% after the activated by boric acid. The specific surface area of BC was significantly increased from 766.6 m·g to 1190.6 m·g. The intensity of the (111) diamond peak of B-BC was higher than that of BC, suggesting that boric acid affected the surface pyrolysis temperature of biochar. The proposed roles of boric acid in the activation process were to: 1) enhance the generation of micropores during the pyrolysis process; 2) improve the yield of biochar via the transformation pathways of C-corresponding bonds and physical blocking. The boric acid activated biochar (B-BC) had a higher adsorption capacity for SMX than BC under the various aqueous conditions. Hence, boric acid activated biochar is a promising porous adsorbent to enhance the removal of SMX and achieve practical application.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127333DOI Listing
September 2021

Polarization-insensitive ultra-short waveguide taper.

Opt Lett 2021 Oct;46(19):5027-5030

Waveguide taper, a key component in the photonic integrated circuit (PIC), enables on-chip mode conversion, but large-footprint tapers are detrimental to the PIC, which desires compact and efficient devices. Polarization sensitivity also limits the tapers in the applications involving orthogonal modes. In this work, we design an efficient polarization-insensitive ultra-short MMI-based waveguide taper, through the mode spreading principle and the self-image principle. The proposed taper is 26.3 µm long, one order of magnitude shorter than the standard linear taper. We fabricate the taper, and experimentally demonstrate that it exhibits a high transmission efficiency of ∼70 and a wide 1 dB bandwidth of >54, for both TE and TM polarizations.
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http://dx.doi.org/10.1364/OL.436223DOI Listing
October 2021

Combined Approach of Compression Molding and Magnetic Attraction to Micropatterning of Magnetic Polydimethylsiloxane Composite Surfaces with Excellent Anti-Icing/Deicing Performance.

ACS Appl Mater Interfaces 2021 Oct 29;13(40):48153-48162. Epub 2021 Sep 29.

Guangdong Provincial Key Laboratory of Functional Soft Condensed Matter, School of Materials and Energy, Guangdong University of Technology, Guangzhou 510006, P. R. China.

The accumulation of ice and contaminants on the surface of composite insulators will cause high energy consumption or even major hazards to power systems. In this work, the polydimethylsiloxane (PDMS) silicone rubber was modified by surface micropatterning and material compositing. Highly crosslinked poly(cyclotriphosphazene--4,4'-sulfonyldiphenol) (PZS) was used to directly coat ferroferric oxide (FeO) nanoparticles. The obtained core-shell [email protected] microspheres were loaded with carbon nanotubes (CNTs) to get CNTs/[email protected] as the photothermal magnetic filler. The PDMS/CNTs/[email protected] surfaces with micronscale truncated cones were prepared via a combined method of compression molding and magnetic attraction. The 1H,1H,2H,2H-perfluorodecyltrichlorosilane-coated template and magnetic field can increase the height of the microstructure to ∼76 μm and maintain the contact angle of microstructured PDMS/CNTs/[email protected] surfaces at a high level (∼152°). Compared with the flat PDMS surface, the micronscale truncated cones extend the freezing time from 4.5 to 11.5 min and also undermine the ice adhesion strength from ∼25 to ∼17 kPa for the microstructured PDMS/CNTs/[email protected] surface. The temperature of the PDMS/CNTs/[email protected] surface molded with magnetic attraction increases linearly with time and the internal magnetic fillers and achieves 280 °C in 10 s. The efficiency of temperature rise is increased by ∼46%, and hence the entire frozen water droplet can melt within 20 s. The strategy combining active deicing with passive anti-icing undoubtedly promotes the development of high efficiency anti-icing materials and can be applied on insulators to prevent icing flashover.
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http://dx.doi.org/10.1021/acsami.1c15428DOI Listing
October 2021

Preparation of Cross-linked Chitosan Quaternary Ammonium Salt Hydrogel Films Loading Drug of Gentamicin Sulfate for Antibacterial Wound Dressing.

Mar Drugs 2021 Aug 25;19(9). Epub 2021 Aug 25.

Key Laboratory of Coastal Biology and Bioresource Utilization, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai 264003, China.

Hydrogels, possessing high biocompatibility and adaptability to biological tissue, show great usability in medical applications. In this research, a series of novel cross-linked chitosan quaternary ammonium salt loading with gentamicin sulfate (CTMCSG) hydrogel films with different cross-linking degrees were successfully obtained by the reaction of chitosan quaternary ammonium salt (TMCS) and epichlorohydrin. Fourier transform infrared spectroscopy (FTIR), thermal analysis, and scanning electron microscope (SEM) were used to characterize the chemical structure and surface morphology of CTMCSG hydrogel films. The physicochemical property, gentamicin sulphate release behavior, cytotoxicity, and antibacterial activity of the CTMCSG against and were determined. Experimental results demonstrated that CTMCSG hydrogel films exhibited good water stability, thermal stability, drug release capacity, as well as antibacterial property. The inhibition zone of CTMCSG hydrogel films against and could be up to about 30 mm. Specifically, the increases in maximum decomposition temperature, mechanical property, water content, swelling degree, and a reduction in water vapor permeability of the hydrogel films were observed as the amount of the cross-linking agent increased. The results indicated that the CTMCSG-4 hydrogel film with an interesting physicochemical property, admirable antibacterial activity, and slight cytotoxicity showed the potential value as excellent antibacterial wound dressing.
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http://dx.doi.org/10.3390/md19090479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8468143PMC
August 2021

Animal models of stroke.

Animal Model Exp Med 2021 Sep 15;4(3):204-219. Epub 2021 Sep 15.

Affiliated Hospital of Guangdong Medical University & Key Laboratory of Zebrafish Model for Development and Diseases of Guangdong Medical University Zhanjiang China.

Stroke is a devastating disease with high morbidity and mortality. Animal models are indispensable tools that can mimic stroke processes and can be used for investigating mechanisms and developing novel therapeutic regimens. As a heterogeneous disease with complex pathophysiology, mimicking all aspects of human stroke in one animal model is impossible. Each model has unique strengths and weaknesses. Models such as transient or permanent intraluminal thread occlusion middle cerebral artery occlusion (MCAo) models and thromboembolic models are the most commonly used in simulating human ischemic stroke. The endovascular filament occlusion model is characterized by easy manipulation and accurately controllable reperfusion and is suitable for studying the pathogenesis of focal ischemic stroke and reperfusion injury. Although the reproducibility of the embolic model is poor, it is more convenient for investigating thrombolysis. Rats are the most frequently used animal model for stroke. This review mainly outlines the stroke models of rats and discusses their strengths and shortcomings in detail.
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http://dx.doi.org/10.1002/ame2.12179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446711PMC
September 2021

Effects of fertilizer under different dripline spacings on summer maize in northern China.

Sci Rep 2021 Sep 23;11(1):18922. Epub 2021 Sep 23.

Key Laboratory of Plant Nutrition and Fertilizer, Ministry of Agriculture and Rural Affairs/ Institute of Agricultural Resources and Regional Planning, Chinese Academy of Agricultural Sciences, 12 South Road, Zhongguancun, Haidian District, Beijing, 100081, People's Republic of China.

Maximizing grain yields with effective fertilization technologies and minimizing nitrogen losses is essential in agroecosystems. In this research, we conducted a two-year field experiment to explore whether dripline spacing and fertilization rate would affect maize grain yield. Two dripline spacings (i.e., one drip line per row of maize with a row space of 60 cm and one drip line per two rows of maize) and two fertilization rates (i.e., high fertilization level: N, 180 kg ha; PO, 90 kg ha; and KO, 90 kg ha and low level: N, 139.5 kg ha; PO, 76.5 kg ha; and KO, 76.5 kg ha) were employed in this research. The results showed that maize yield was significantly affected by both dripline spacing and fertilization rate. The maize yield was 10.2% higher in the treatment with one drip line per two rows than that in the treatment with one drip line per row. Maize yield increased by 10.9% at the high fertilization level compared to that at the low fertilization level. The quantity of cumulative ammonia volatilization was reduced by 15.1% with one drip line per two rows compared to that with one drip line per row, whereas it increased by 26.9% at the high fertilization level compared with that at the low fertilization level. These results indicated that one drip line per two rows with a high fertilization rate increased the yield and could reduce the environmental burden, which may be economically beneficial and environmentally sound for maize fertigation for green agricultural development.
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http://dx.doi.org/10.1038/s41598-021-98016-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8460782PMC
September 2021

HM-3-HSA exhibits potent anti-angiogenesis and antitumor activity in hepatocellular carcinoma.

Eur J Pharm Sci 2021 Sep 21;167:106017. Epub 2021 Sep 21.

Institute of Microbiology, School of Life Sciences, Lanzhou University, Lanzhou 730000, China; Gansu High Throughput Screening and Creation Center for Health Products, School of Pharmacy, Lanzhou University, Lanzhou 730000, China. Electronic address:

HM-3-HSA is an antitumor fusion protein which improved the pharmacokinetics of HM-3. Previous studies reported that HM-3-HSA enhanced antitumor activity of HM-3 in melanoma cells. However, the efficacy and the mechanism of HM-3-HSA in hepatocellular carcinoma, especially its effect on tumor angiogenesis, have not been elucidated. Herein, we showed that HM-3-HSA significantly inhibited the H22 and SMMC-7721 tumor xenografts growth and tumor angiogenesis in vivo, indicating the antitumor activity exerted by HM-3-HSA was closely corrected with its potency on tumor angiogenesis. To investigate the anti-angiogenic mechanism, we evaluated the efficacy of HM-3-HSA in HUVECs in vitro. The results showed that multiple steps of tumor angiogenesis, including endothelial cell proliferation, migration, invasion and tube formation, were substantially inhibited by HM-3-HSA. Mechanism investigations revealed that HM-3-HSA could bind HUVECs via integrin αvβ3 and α5β1 and inhibited phosphorylation of the downstream protein kinases including FAK, Src and PI3 K. Our study was the first to report the activity of HM-3-HSA against hepatocellular carcinoma and tumor angiogenesis as well as the underlying mechanism by which HM-3-HSA to exert its anti-angiogenic activity.
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http://dx.doi.org/10.1016/j.ejps.2021.106017DOI Listing
September 2021

Fabrication of hydrophilic zwitterionic microspheres via inverse suspension polymerization for the enrichment of N-glycopeptides.

Mikrochim Acta 2021 09 20;188(10):348. Epub 2021 Sep 20.

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.

A kind of zwitterionic microsphere was prepared via one-step inverse suspension polymerization employing 3-[N,N-dimethyl-[2-(2-methylpropyl-2-enyloxy) ethyl] ammonium] propane-1-sulfonate (MSA) and N,N-methylene bisacrylamide (BIS) as the precursors. The preparation conditions were carefully investigated and optimized by regulating the content of total monomers, ratio of MSA to BIS, ratio of water to oil, and content of stabilizer. The properties of microspheres were characterized by helium ion microscopy (HIM), Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS), N adsorption/desorption measurement, and water contact angle measurement. The particle size of resulting polydisperse microspheres ranged from 15-25 μm, exhibiting high specific surface area of 138 m g. Owing to great hydrophilicity, the resulting zwitterionic microspheres could be directly used as hydrophilic interaction chromatography (HILIC) sorbent to enrich glycopeptides from biosamples without any chemical modification. A total of 19 N-glycopeptides was enriched from 10 μg of IgG digest. Besides, up to 383 N-glycopeptides and 224 N-glycosylation sites were unambiguously identified from 2 μL of human serum digest by cLC-MS/MS after enrichment with zwitterionic microspheres, indicating their great enrichment performance to N-glycopeptides. The approach of preparing hydrophilic zwitterionic microspheres contains only one synthesis reaction and is suitable for large-scale preparation.
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http://dx.doi.org/10.1007/s00604-021-05010-wDOI Listing
September 2021

Claudin-5 Affects Endothelial Autophagy in Response to Early Hypoxia.

Front Physiol 2021 31;12:737474. Epub 2021 Aug 31.

Affiliated Hospital of Guangdong Medical University & Key Laboratory of Zebrafish Model for Development and Disease of Guangdong Medical University, Zhanjiang, China.

Hypoxic injury to cerebrovascular endothelial cells (ECs) after stroke leads to blood-brain barrier (BBB) dysfunction, which is commonly associated with disruptions of endothelial tight junctions (TJs) and increased permeability. Therefore, maintaining the structural integrity and proper function of the BBB is essential for the homeostasis and physiological function of the central nervous system (CNS). Our previous study revealed that autophagy functions on protecting the BBB by regulating the dynamics of Claudin-5, the essential TJ protein, under short-term starvation or hypoxia conditions. Here, we show that in zebrafish and cells, loss of membranous Claudin-5 conversely determine the occurrence of hypoxia-induced autophagy in cerebrovascular ECs. Absence of endothelial Claudin-5 could partly attenuate endothelial cell apoptosis caused by short-term hypoxic injury. Mechanism studies revealed that under hypoxic conditions, the existence of membranous Claudin-5 affects the stimulation of hypoxia inducible factor 1 subunit alpha (HIF-1a) and the inducible nitric oxide synthase (iNOS), which are responsible for the translocation of and endocytosis of caveole-packaged Claudin-5 into cytosol. Meanwhile, loss of Claudin-5 affects the generation of reactive oxygen species (ROS) and the downstream expression of BCL2/adenovirus E1B 19kDa protein interacting protein 3 (Bnip3). These together suppress the endothelial autophagy under hypoxia. This finding provides a theoretical basis for clarifying the mechanism of hypoxia-induced BBB injury and its potential protection mechanisms.
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http://dx.doi.org/10.3389/fphys.2021.737474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438321PMC
August 2021

Selenite induced breast cancer MCF7 cells apoptosis through endoplasmic reticulum stress and oxidative stress pathway.

Chem Biol Interact 2021 Nov 11;349:109651. Epub 2021 Sep 11.

Department of Nutrition, School of Public Health, Xuzhou Medical University, China. Electronic address:

Selenium is an essential trace element for human, and has anti-tumor effects. In this study, we investigated the anti-tumor activity of sodium selenite (NaSeO) and explored its possible mechanisms involved in a breast cancer cell line. We found that NaSeO could inhibit the cell viability of MCF7 cells, yet with minimal damage to human umbilical vein endothelial cells (HUVECs). The results of Hoechst staining and Western Blot showed that NaSeO induced apoptosis of MCF7 cells. NaSeO activated endoplasmic reticulum stress (ERS), as evidenced by the up-regulation of ERS-related proteins, including ATF6, p-eIF2α, ATF4, and CHOP, and the down-regulation of PERK. ATF6, p-eIF2α and apoptosis were decreased by pre-treatment with an ERS inhibitor (4-PBA). NaSeO activated oxidative stress (OS) through increasing ROS generation and decreasing mitochondrial membrane potential (MMP) which induced apoptosis. Pre-treatment with an antioxidant (NAC) attenuated NaSeO-induced OS and cell apoptosis. Furthermore, ERS and OS had mutual effects. Pre-treatment with 4-PBA could act against the up-regulation of ROS and the down-regulation of MMP. Pre-treatment with NAC attenuated the expression of ATF6. At the same time, we found that treatment with NaSeO promoted the phosphorylation of p38 and JNK, while inhibiting the phosphorylation of ERK. However, the up-regulation was inhibited after pre-treatment of NAC, and pre-treatment with 4-PBA inhibited the increase only of p38. Based on these results, our study provides a mechanistic understanding of how NaSeO has antitumor effects against MCF7 cells through the OS and ERS pathway. OS and ERS interact with each other, and p38 is regulated by them.
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http://dx.doi.org/10.1016/j.cbi.2021.109651DOI Listing
November 2021

Metabolic Surgery Improves the Unbalanced Proportion of Peripheral Blood Myeloid Dendritic Cells and T Lymphocytes in Obese Patients.

Eur J Endocrinol 2021 Sep 1. Epub 2021 Sep 1.

Z Zhou, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, 410011, China.

Background: Obesity is associated with impaired immune function and chronic low-grade inflammation. Metabolic surgery is one of the most effective therapies for treating obesity and related metabolic disorders. We aimed to explore the pathophysiological roles of peripheral DCs and T lymphocytes in metabolic surgery.

Method: In this observational cohort study, a total of 106 individuals, including obese participants with or without T2DM, overweight subjects and normal controls, were recruited. All obese participants underwent laparoscopic sleeve gastrectomy surgery and returned for evaluation of the clinical indicators after surgery. We evaluated the frequencies of circulating DCs subsets (mDCs and pDCs), the pro-inflammatory (Th1 and Th17) and antiinflammatory (Th2 and Treg) T cell subsets by flow cytometry.

Results: Compared with the normal controls, the frequencies of mDCs, Th1 and Th17 cells increased, while Treg and Th2 cells decreased in the obese participants. The frequency of mDCs and Th1 cells consistently declined after surgery compared with baseline in the obese patients and were restored to the levels observed in the normal controls after surgery. Moreover, the frequency of Treg cells was increased at 6 months after surgery in the obese patients with T2DM, and Th17 cells declined at 6 months after surgery in the severely obese patients without T2DM.

Conclusion: This study indicates that metabolic surgery can effectively improve imbalanced immune cells in peripheral blood and restore the proportion of immune cells to a normal range during a 12-month follow-up.
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http://dx.doi.org/10.1530/EJE-21-0620DOI Listing
September 2021
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