Publications by authors named "Hui Xiao"

453 Publications

The effectiveness of axillary reverse mapping in preventing breast cancer-related lymphedema: a meta-analysis based on randomized controlled trials.

Gland Surg 2021 Apr;10(4):1447-1459

Department of Breast Disease, Henan Breast Cancer Center, The affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.

Background: Here, we carried out an extensive meta-analysis to investigate the effectiveness of the use of axillary reverse mapping (ARM) during axillary lymph node dissection (ALND) in preventing breast cancer-related lymphedema (BCRL).

Methods: Database searches to identify relevant randomized controlled trials (RCTs) were performed of MEDLINE (PubMed), Web of Science, Embase, and the Cochrane Library. Eligible articles with a publication date from database establishment to December 2020 were retrieved by combining keywords including: "breast cancer", "breast carcinoma", "breast neoplasm", "axillary reverse mapping", "axillary lymph node dissection", "lymphatic arm drainage", and "lymphedema". Independent data extraction was conducted, and Review Manager (version 5.3) was used for statistical analyses.

Results: Five eligible RCTs were included in the meta-analysis. A total of 37 patients suffered arm lymphedema (37/786, 4.71%) in the experimental group (ARM during ALND), compared with 164 arm lymphedemas (164/873, 18.79%) in the control group (ALND alone). The results showed that ARM during ALND was superior to ALND alone in reducing the incidence of BCRL [OR =0.20, 95% confidence intervals (CI): 0.13-0.29, P<0.00001]; however, the 2 procedures did not differ significantly in terms of oncological safety or shoulder movement (OR =0.30, 95% CI: 0.03-2.96, P=0.30; OR =0.44, 95% CI: 0.14-1.40, P=0.17).

Conclusions: ARM during ALND can prevent and reduce the occurrence of BCRL in patients with early-stage BC during long-term follow-up. Due to the limited number of RCTs available, more in-depth, high-quality RCTs are urgently needed to provide a reliable and convincing basis for the application of ARM during ALND.
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http://dx.doi.org/10.21037/gs-21-186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102224PMC
April 2021

Three new species of the genus (Hymenoptera, Chalcidoidea, Eurytomidae) from China.

Zookeys 2021 8;1029:123-137. Epub 2021 Apr 8.

Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China Key Laboratory of Zoological Systematics and Evolution, Institute of Zoology, Chinese Academy of Sciences Beijing China.

Three new species of Walker (Hymenoptera, Eurytomidae), , and , are reported and described from mainland China. Meanwhile, Melika & Tang, 2011 (Hymenoptera, Cynipidae) is reported as a new host record of the genus . A key to Chinese and illustrations of external features of the species are provided.
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http://dx.doi.org/10.3897/zookeys.1029.60911DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050019PMC
April 2021

Glycogen synthase kinase-3β (GSK-3β) deficiency inactivates the NLRP3 inflammasome-mediated cell pyroptosis in LPS-treated periodontal ligament cells (PDLCs).

In Vitro Cell Dev Biol Anim 2021 Apr 27. Epub 2021 Apr 27.

Department of Orthodontics, Stomatological Hospital, Southern Medical University, Jiangnan South Avenue No. 366, Guangzhou, 510260, Guangdong, China.

Bacterial infection caused cell pyroptosis and gingival inflammation contributes to periodontitis progression, and lipopolysaccharide (LPS) is the main infectious agent of gram-negative bacteria, which is reported to be closely associated with gingival inflammation and periodontitis. In this study, the primary human periodontal ligament cells (PDLCs) were isolated, cultured, and exposed to LPS treatment, and the results suggested that LPS suppressed cell viability and promoted pro-inflammatory cytokines' (IL-1β, IL-18, IL-6, and TNF-α) generation and secretion in the PDLCs and its supernatants in a time- and concentration-dependent manner. Also, we noticed that LPS upregulated NLRP3, Gasdermin D, and cleaved caspase-1 to trigger pyroptotic cell death in the PDLCs. Further experiments identified that glycogen synthase kinase-3β (GSK-3β) was upregulated by LPS treatment, and inhibition of GSK-3β by its inhibitor (GSKI) or GSK-3β downregulation vectors was effective to restore normal cellular functions in LPS-treated PDLCs. Mechanistically, blockage of GSK-3β restrained NLRP3-meidated cell pyroptosis and inflammation, resulting in the recovery of cell viability and inhibition of cell death in PDLCs treated with LPS, which further ameliorated periodontitis progression. Finally, we collected the serum from periodontitis patients and healthy volunteers, and the clinical data supported that those pro-inflammatory cytokines were also upregulated in patients' serum but not in the healthy participants. Taken together, we concluded that targeting the GSK-3β/NLRP3 pathway mediated cell pyroptosis was effective to attenuate LPS-induced cell death and inflammation in PDLCs, and this study firstly investigated this issue, which broadened our knowledge in this field.
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http://dx.doi.org/10.1007/s11626-021-00583-5DOI Listing
April 2021

Retraction: Nanozyme-Initiated In Situ Cascade Reactions for Self-Amplified Biocatalytic Immunotherapy.

Adv Mater 2021 Apr;33(16):e2101383

Adv. Mater. 2021, 33, 2006363 DOI: 10.1002/adma.202006363 The above article, published online on December 6, 2020, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors, the journal Editor in Chief Jos Lenders, and Wiley-VCH GmbH. The authors asked to retract this article as subsequent experiments revealed that the conclusions of this manuscript are invalid. The generation of hydroxyl radicals by the artificial cascade enzyme-drug conjugate could not be confirmed.
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http://dx.doi.org/10.1002/adma.202101383DOI Listing
April 2021

Experimental Study of lncRNA RP11-815M8.1 Promoting Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells.

Biomed Res Int 2021 26;2021:5512370. Epub 2021 Mar 26.

Department of Orthodontics, Stomatological Hospital, Southern Medical University (Guangdong Provincial Stomatological Hospital), Guangzhou, Guangdong 510280, China.

Objective: This study is aimed at investigating the role of long noncoding RNA (lncRNA) RP11-815M8.1 in the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs).

Methods: RT-PCR was used to detect the expression of lncRNA RP11-815M8.1 before and after osteogenic differentiation of hBMSCs. The lncRNA RP11-815M8.1 in hBMSCs was overexpressed or silenced via lentiviral transfection. The transfection efficiency was detected by RT-PCR, and the proliferation of hBMSCs was determined by CCK-8. After 14 days of osteogenic differentiation of transfected hBMSCs, the expression of osteogenic transcription factors (ALP, OCN, OPN, Runx2, and Osterix) was detected by alizarin red staining and RT-PCR. The mRNAs directly regulated by lncRNA RP11-815M8.1 and targeted miRNAs were analyzed according to the positional relationship between lncRNA and mRNA in the genome and miRanda software.

Results: The expression of lncRNA RP11-815M8.1 enhanced with increasing osteogenic differentiation time of hBMSCs. Two days after the transfection of hBMSCs, lncRNA RP11-815M8.1 expression was significantly increased in the overexpression group and significantly decreased in the knockdown group, compared to control cells. The CCK-8 assay showed that overexpression and knockdown of lncRNA RP11-815M8.1 did not affect the proliferation of hBMSCs. After 14 days of differentiation of hBMSCs, stronger alizarin red staining was observed in the overexpression groups, and the expression of osteogenic transcription factors was increased in the overexpression group compared to the control. In the knockdown group, alizarin red staining and the expression of osteogenic transcription factors were decreased. Bioinformatics analysis showed that lncRNA RP11-815M8.1 was directly associated with one mRNA, 27 interacting miRNAs, and 20 miRNA-targeted mRNAs.

Conclusion: The osteogenic differentiation of hBMSCs can be promoted by lncRNA RP11-815M8.1 in vitro.
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http://dx.doi.org/10.1155/2021/5512370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019361PMC
March 2021

Regulation of Anion Channel LRRC8 Volume-Regulated Anion Channels in Transport of 2'3'-Cyclic GMP-AMP and Cisplatin under Steady State and Inflammation.

J Immunol 2021 May 7;206(9):2061-2074. Epub 2021 Apr 7.

The Center for Microbes, Development and Health, Chinese Academy of Sciences Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China;

The recently identified anion channel LRRC8 volume-regulated anion channels (VRACs) are heteromeric hexamers constituted with the obligate LRRC8A subunit paired with at least one of the accessory LRRC8B to LRRC8E subunits. In addition to transport chloride, taurine, and glutamate, LRRC8 VRACs also transport the anticancer agent cisplatin and STING agonists 2'3'-cyclic GMP-AMP (cGAMP) and cyclic dinucleotides; hence, they are implicated in a variety of physiological and pathological processes, such as cell swelling, stroke, cancer, and viral infection. Although the subunit composition largely determines VRAC substrate specificity, the opening of various VRAC pores under physiological and pathological settings remains enigmatic. In this study, we demonstrated that VRACs comprising LRRC8A and LRRC8E (LRRC8A/E-containing VRACs), specialized in cGAMP transport, can be opened by a protein component present in serum under resting condition. Serum depletion ablated the tonic activity of LRRC8A/E-containing VRACs, decreasing cGAMP transport in various human and murine cells. Also, heating or proteinase K treatment abolished the ability of serum to activate VRAC. Genetic analyses revealed a crucial role for cGAMP synthase (cGAS) in serum/TNF-promoted VRAC activation. Notably, the presence of cGAS on the plasma membrane, rather than its DNA-binding or enzymatic activity, enabled VRAC activation. Moreover, phospholipid PIP2 seemed to be instrumental in the membrane localization of cGAS and its association with VRACs. Corroborating a role for LRRC8A/D-containing VRACs in cisplatin transport, serum and TNF markedly potentiated cisplatin uptake and killing of cancer cells derived from human or mouse. Together, these observations provide new insights into the complex regulation of VRAC activation and suggest a novel approach to enhance the efficacy of cGAMP and cisplatin in treating infection and cancer.
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http://dx.doi.org/10.4049/jimmunol.2000989DOI Listing
May 2021

The Effects of Bioactive Compounds from Blueberry and Blackcurrant Powder on Oat Bran Pastes: Enhancing In Vitro Antioxidant Activity and Reducing Reactive Oxygen Species in Lipopolysaccharide-Stimulated Raw264.7 Macrophages.

Antioxidants (Basel) 2021 Mar 5;10(3). Epub 2021 Mar 5.

Department of Wine, Food and Molecular Biosciences, Faculty of Agriculture & Life Sciences, Lincoln University, Christchurch 7647, New Zealand.

In this study, blueberry and blackcurrant powder were chosen as the phenolic-rich enrichments for oat bran. A Rapid Visco Analyser was used to form blueberry and blackcurrant enriched oat pastes. An in vitro digestion process evaluated the changes of phenolic compounds and the in vitro antioxidant potential of extracts of pastes. The anthocyanidin profiles in the extracts were characterised by the pH differential method. The results showed that blueberry and blackcurrant powder significantly increased the content of phenolic compounds and the in vitro antioxidant capacity of pastes, while the total flavonoid content decreased after digestion compared to the undigested samples. Strong correlations between these bioactive compounds and antioxidant values were observed. Lipopolysaccharide-stimulated RAW264.7 macrophages were used to investigate the intracellular antioxidant activity of the extracts from the digested oat bran paste with 25% enrichment of blueberry or blackcurrant powder. The results indicated that the extracts of digested pastes prevented the macrophages from experiencing lipopolysaccharide (LPS)-stimulated intracellular reactive oxygen species accumulation, mainly by the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signalling pathway. These findings suggest that the bioactive ingredients from blueberry and blackcurrant powder enhanced the in vitro and intracellular antioxidant capacity of oat bran pastes, and these enriched pastes have the potential to be utilised in the development of the functional foods.
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http://dx.doi.org/10.3390/antiox10030388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7998505PMC
March 2021

Wide-range optical fiber temperature sensor based on up-conversion luminescent nanocrystals.

Opt Lett 2021 Apr;46(7):1600-1603

In this study, an optical fiber temperature sensor based on up-conversion luminescence (UCL) is proposed. The core part is a new plan of the sensing unit, which is constructed with UCL materials of : , nanocrystals by fiber fusion technology to achieve a wide range of temperature measurements. Experimental results show that the proposed optical fiber temperature sensor shows significant spectrum-temperature characteristics in 80-373 K temperature range. Its relative sensitivities at low temperature and normal temperature are 2.2×10/ with a determination coefficient of 0.957 and 9.1×10/ with a determination coefficient of 0.994, respectively. This type of sensor also has good mechanical strength and system stability and shows great potential for development, particularly in the aerospace field with large temperature differences.
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http://dx.doi.org/10.1364/OL.419059DOI Listing
April 2021

Optical coherence tomography angiography helps distinguish multiple sclerosis from AQP4-IgG-seropositive neuromyelitis optica spectrum disorder.

Brain Behav 2021 May 30;11(5):e02125. Epub 2021 Mar 30.

Department of Neurology, Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Introduction: The aim was to characterize the optical coherence tomography (OCT) angiography measures in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) and to evaluate their disease discrimination capacity.

Methods: Patients with MS (n = 83) and AQP4-IgG-seropositive NMOSD (n = 91) with or without a history of optic neuritis, together with healthy controls (n = 34), were imaged. The main outcome measures were peripapillary retinal nerve fiber layer (pRNFL) thickness, macular ganglion cell-inner plexiform layer (GC-IPL) thickness, macular vessel density (VD), and perfusion density (PD) in the superficial capillary plexus. Diagnostic accuracy was assessed using the area under the receiver operating characteristics curve.

Results: Compared with patients with MS, those with NMOSD had a significantly smaller average thickness of the pRNFL and GC-IPL (80.0 [59.0; 95.8] μm versus 92.0 [80.2; 101] μm, p < .001; 68.0 [56.0; 81.0] μm, versus 74.5 [64.2; 81.0] μm, p < .001) and significantly smaller whole VD and PD areas (15.6 [12.6; 17.0] mm versus 16.7 [14.8; 17.7] mm , p < .001; 0.38 [0.31; 0.42] mm versus 0.40 [0.37; 0.43] mm , p < .01). The combination of structural parameters (average thickness of the pRNFL and GC-IPL) with microvascular parameters (temporal-inner quadrant of VD, temporal-inner, nasal-inferior, and nasal-outer quadrant of PD) was revealed to have a good diagnostic capability for discriminating between NMOSD and MS.

Conclusions: OCT angiography reveals different structural and microvascular retinal changes in MS and AQP4-IgG-seropositive NMOSD. These combined structural and microvascular parameters might be promising biomarkers for disease diagnosis.
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http://dx.doi.org/10.1002/brb3.2125DOI Listing
May 2021

A Novel Normalized Cross-Correlation Speckle-Tracking Ultrasound Algorithm for the Evaluation of Diaphragm Deformation.

Front Med (Lausanne) 2021 12;8:612933. Epub 2021 Mar 12.

Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, China.

To develop a two-dimensional normalized cross-correlation (NCC)-based ultrasonic speckle-tracking algorithm for right diaphragm deformation analysis. Six healthy and eight mechanical ventilation patients were enrolled in this study. Images were acquired by a portable ultrasound system in three sections. DICOM data were processed with NCC to obtain the interframe/cumulative vertical and horizontal displacements, as well as the global strain of the right diaphragm, with continuous tracking and drift correction. The NCC algorithm can track the contraction and relaxation of the right diaphragm by following the respiratory movement continuously. For all three sections, the interframe and accumulated horizontal displacements were both significantly larger than the corresponding vertical displacements (interframe values: 0.031, 0.004, and 0.000; cumulative values: 0.039, 0.001, and <0.0001). For the global strain of the right diaphragm, there was no significant difference between each pair of sections (all > 0.05), regardless of whether the horizontal interval of the initial diaphragm point was 1, 3, 5, or 10 times in the sampling interval. This study developed a novel diaphragm deformation ultrasound imaging method. This method can be used to estimate the diaphragm interframe/accumulated displacement in the horizontal and vertical directions and the global strain on three different imaging planes, and it was found that the strain was not sensitive to the imaging plane.
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http://dx.doi.org/10.3389/fmed.2021.612933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994279PMC
March 2021

Effect of nursing intervention to guide early postoperative activities on rapid rehabilitation of patients undergoing abdominal surgery: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Mar;100(12):e24776

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China.

Background: Postoperative complications after abdominal surgery are high, and there is no reliable intervention program to prevent them. Some studies have pointed out that early postoperative activities have advantages in preventing the occurrence of complications, but lack of evidence-based basis. The purpose of this study is to systematically evaluate the effect of nursing intervention is guiding early postoperative activities on the rapid recovery of patients undergoing abdominal surgery.

Methods: China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database and Chinese Biomedical Database, PubMed, Embase, Web of Science and the Cochrane Library will be searched by computer, and a randomized controlled study is conducted on early participation in exercise programs after abdominal surgery from the establishment of the database to January 2021. The language is limited to English and Chinese. The quality of the included study is independently extracted and the literature quality is evaluated by 2 researchers, and the included literature is analyzed by Meta using RevMan5.3 software.

Results: This study will evaluate the effect of nursing intervention is guiding early postoperative activities on the rapid rehabilitation of patients undergoing abdominal surgery through the indexes of postoperative quality of life score, the incidence of complications, mortality, length of stay and so on.

Conclusion: This study will provide reliable evidence-based basis for establishing a reasonable and effective postoperative activity guidance program for patients undergoing abdominal surgery.

Ethics And Dissemination: Private information from individuals will not be published. This systematic review also does not involve endangering participant rights. Ethical approval will not be required. The results may be published in a peer-reviewed journal or disseminated at relevant conferences.

Osf Registration Number: DOI 10.17605/OSF.IO/59MD4.
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http://dx.doi.org/10.1097/MD.0000000000024776DOI Listing
March 2021

Precision control of mTORC1 is crucial for the maintenance and IL-13 responsiveness of alveolar macrophages.

Int Immunopharmacol 2021 Jun 17;95:107552. Epub 2021 Mar 17.

CAS Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, CAS Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address:

Alveolar macrophages (AMs) are the lung resident macrophages critically involved in pulmonary homeostasis and immune response. Recent researches have uncovered a diversity of regulators responsible for the development, maintenance, and function of AMs. Nevertheless, the molecular underpinnings that determine the developmental and functional specification of AMs remain incompletely understood. Here, we investigated the role of the TSC1-mTOR pathway in murine AMs by genetic ablating Tsc1 or mTor alleles through Cd11c-Cre or LysM-Cre. Flow cytometry analyses revealed a prominent decrease in AMs in Tsc1 and Tsc1 mice. Moreover, a reduction in AMs was also noted in mTor or Rptor mice. Further evidence implicated that elevation in cell death, most likely aberrant apoptosis or/and necroptosis, might be attributable to disrupted AM homeostasis. Whereas a diversity of cytokines involved in AM homeostasis and function triggered mTOR activation, only the IL-13 signaling, particularly Jak1 and Stat3 activation, was affected by TSC1 in macrophages. Further, select genes induced by IL-13, including AM surface markers such as Pparg, Fabp4/5, Nfil3 and Car4, and M2 hallmarks such as Arg1, Fizz, Ym1 and Clec7a were fine-tuned by the TSC1-mTOR pathway. Therefore, our results demonstrated that the TSC1-mTOR pathway has a crucial role in the homeostasis and functional specification of AMs through integrating cytokine signaling with metabolic cues.
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http://dx.doi.org/10.1016/j.intimp.2021.107552DOI Listing
June 2021

Mn/Mn co-doped LaMAlO (M = Mg, Zn) luminescent materials: electronic structure, energy transfer and optical thermometric properties.

Dalton Trans 2021 Apr 16;50(13):4651-4662. Epub 2021 Mar 16.

Key Laboratory of In-Fiber Integrated Optics, Ministry Education of China, and College of Physics and Opotoelectronic Engineering, Harbin Engineering University, Harbin 150001, China.

Dual-emitting manganese ion doped LaMAlO (M = Mg, Zn) phosphors were prepared by substituting Zn/Mg with Mn and replacing Al with Mn. The LaMAlO:xMn,yMn phosphors show a narrow green emission band of the Mn ions at 514 nm and a red emission band of the Mn ions at 677 nm. In addition, the thermal stability of luminescence shows that the response of Mn and Mn to the temperature is obviously different in LaMAlO, implying the potential of the prepared phosphors as optical thermometers. The decay lifetime of Mn was changed with temperature due to the different fluorescence intensity ratios of Mn and Mn, and a dual-mode optical temperature-sensing mechanism was studied in the temperature range of -50-200 °C. The maximum relative sensitivities (S) are calculated as 3.22 and 3.13% K, respectively. The unique optical thermometric features demonstrate the application potential of LaMAlO:Mn,Mn in optical thermometry.
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http://dx.doi.org/10.1039/d1dt00153aDOI Listing
April 2021

Activation of ATF4 triggers trabecular meshwork cell dysfunction and apoptosis in POAG.

Aging (Albany NY) 2021 03 10;13(6):8628-8642. Epub 2021 Mar 10.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Primary open angle glaucoma (POAG) is the leading cause of irreversible blindness. Dysfunction of the trabecular meshwork (TM), resulting in decreased outflow of aqueous humor and increased intraocular pressure (IOP), plays an important role in the pathogenesis of POAG. However, the underlying mechanisms still remain unclear. In this study, we demonstrated that the eIF2-α/ATF4/CHOP branch of unfolded protein response (UPR) was activated in human trabecular meshwork cells (HTMCs) upon tert-butyl hydroperoxide (TBHP) exposure. Inhibition of ATF4 ameliorated TBHP-induced apoptosis and inflammatory cytokine production, while ectopic expression of ATF4 increased the expression of endothelial leukocyte adhesion molecule (ELAM)-1 and IL-8 in HTMCs. Furthermore, we found that ATF4 inhibition reduced tunicamycin-induced caspase-3 activation, ROS production, ELAM-1 expression, and HTMCs phagocytosis impairment. By an study in mice, we showed that overexpression of ATF4 in the TM induced C/EBP homologous protein (CHOP) expression and TM cells apoptosis, contributing to inflammatory cytokine production, and probably IOP elevation. More importantly, upregulation of ATF4 and CHOP, and colocalization of ATF4 with ELAM-1 were found in the TM of POAG patients. These results suggest that ATF4 is a critical mediator of oxidative stress and ER stress-induced TM cell dysfunction and apoptosis in POAG.
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http://dx.doi.org/10.18632/aging.202677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034903PMC
March 2021

Effects of Different Short-Term UV-B Radiation Intensities on Metabolic Characteristics of .

Int J Mol Sci 2021 Feb 22;22(4). Epub 2021 Feb 22.

College of Marine Life Sciences, Ocean University of China, Qingdao 266000, China.

The effects of ultraviolet (UV) radiation, particularly UV-B on algae, have become an important issue as human-caused depletion of the protecting ozone layer has been reported. In this study, the effects of different short-term UV-B radiation on the growth, physiology, and metabolism of were examined. The growth of decreased, and the bleaching phenomenon occurred in the thalli. The contents of total amino acids, soluble sugar, total protein, and mycosporine-like amino acids (MAAs) increased under different UV-B radiation intensities. The metabolic profiles of differed between the control and UV-B radiation-treated groups. Most of the differential metabolites in were significantly upregulated under UV-B exposure. Short-term enhanced UV-B irradiation significantly affected amino acid metabolism, carbohydrate metabolism, glutathione metabolism, and phenylpropane biosynthesis. The contents of phenylalanine, tyrosine, threonine, and serine were increased, suggesting that amino acid metabolism can promote the synthesis of UV-absorbing substances (such as phenols and MAAs) by providing precursor substances. The contents of sucrose, D-glucose-6-phosphate, and beta-D-fructose-6-phosphate were increased, suggesting that carbohydrate metabolism contributes to maintain energy supply for metabolic activity in response to UV-B exposure. Meanwhile, dehydroascorbic acid (DHA) was also significantly upregulated, denoting effective activation of the antioxidant system. To some extent, these results provide metabolic insights into the adaptive response mechanism of to short-term enhanced UV-B radiation.
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http://dx.doi.org/10.3390/ijms22042180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927003PMC
February 2021

Environmental enrichment implies GAT-1 as a potential therapeutic target for stroke recovery.

Theranostics 2021 27;11(8):3760-3780. Epub 2021 Jan 27.

Department of Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

Stroke is a leading cause of adult disability worldwide, but no drug provides functional recovery during the repair phase. Accumulating evidence demonstrates that environmental enrichment (EE) promotes stroke recovery by enhancing network excitability. However, the complexities of utilizing EE in a clinical setting limit its translation. We used multifaceted approaches combining electrophysiology, chemogenetics, optogenetics, and floxed mice in a mouse photothrombotic stroke model to reveal the key target of EE-mediated stroke recovery. EE reduced tonic gamma-aminobutyric acid (GABA) inhibition and facilitated phasic GABA inhibition in the peri-infarct cortex, thereby promoting network excitability and stroke recovery. These beneficial effects depended on GAT-1, a GABA transporter regulating both tonic and phasic GABA signaling, as EE positively regulated GAT-1 expression, trafficking, and function. Furthermore, GAT-1 was necessary for EE-induced network plasticity, including structural neuroplasticity, input synaptic strengthening in the peri-infarct cortex, output synaptic strengthening in the corticospinal tract, and sprouting of uninjured corticospinal axons across the midline into the territory of denervated spinal cord, and functional recovery from stroke. Moreover, restoration of GAT-1 function in the peri-infarct cortex by its overexpression showed similar beneficial effects on stroke recovery as EE exposure. GAT-1 is a key molecular substrate of the effects of EE on network excitability and consequent stroke recovery and can serve as a novel therapeutic target for stroke treatment during the repair phase.
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http://dx.doi.org/10.7150/thno.53316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914370PMC
January 2021

Effects of temperature on growth, development and the leptin signaling pathway of Bufo gargarizans.

J Therm Biol 2021 Feb 29;96:102822. Epub 2020 Dec 29.

College of Life Science, Shaanxi Normal University, Xi'an, 710119, China. Electronic address:

Climate change is one of the most important causes of the decline in amphibians. Changes in temperature have an important effect on the growth and development and energy metabolism of amphibians. The aim of this study is to unravel the effects of temperature on the leptin signaling pathway of Bufo gargarizans and its molecular mechanisms. Our results showed that high temperature accelerated the development rate of tadpoles, but reduced body size and mass, while low temperature deferred the development of tadpoles, but increased size and mass. Both high temperature and low temperature exposure caused pathological damage of the liver in B. gargarizans. The results of RT-qPCR revealed that the high temperature treatment significantly upregulated the transcript levels of genes related to thyroid hormone (DIO2 (D2), Thyroid Hormone Receptor-α (TRα)) and the leptin signaling pathway (Leptin Receptor (LepR), Janus kinase 1 (JAK1), Janus kinase 2 (JAK2), Tyrosine kinase 2 (TYK2), Signal Transducer And Activator Of Transcription 3 (STAT3), Signal Transducer And Activator Of Transcription 3.1 (STAT3.1), and Signal Transducer And Activator Of Transcription 6 (STAT6)), while there was a decrease of mRNA expression of these genes (TRα, Thyroid Hormone Receptor-Beta (TRβ), LepR, JAK1, and TYK2) in the liver of tadpoles exposed to high temperature compared with the intermediate temperature treatment. Therefore, our results suggested that temperature extremes might interfere with the thyroid and leptin signaling pathways and affect the growth and development of B. gargarizans. Furthermore, tissue injury of the liver could occur due to exposure to temperature extremes. This work promotes public awareness of environmental protection and species conservation needs, also provides valuable experimental data and a theoretical basis for the protection of amphibians.
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http://dx.doi.org/10.1016/j.jtherbio.2020.102822DOI Listing
February 2021

Practice in Information Technology Support for Fangcang Shelter Hospital during COVID-19 Epidemic in Wuhan, China.

J Med Syst 2021 Feb 19;45(4):42. Epub 2021 Feb 19.

Information Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

In confronting the sudden epidemic of COVID-19, China and other countries have been under great deal of pressure to block virus transmission and reduce death cases. Fangcang shelter hospital, which is converted from large-scale public venue, is proposed and proven to be an effective way for administering medical care and social isolation. This paper presents the practice in information technology support for a Fangcang shelter hospital in Wuhan, China. The experiences include the deployment strategy of IT infrastructure, the redesign of function modules in the hospital information system (HIS), equipment maintenance and medical staff training. The deployment strategy and HIS modules have ensured smoothness and efficiency of clinical work. The team established a quick response mechanism and adhered to the principle of nosocomial infection control. Deployment of network and modification of HIS was finished in the 48 hours before patient admittance. A repair hotline and remote support for equipment and software were available whenever medical workers met with any questions. No engineer ever entered the contaminated areas and no one was infected by the coronavirus during the hospital operation. Up to now, Fangcang shelter hospital is adopted by many regions around the world facing the collapse of their medical systems. This valuable experience in informatization construction and service in Wuhan may help participators involving in Fangcang shelter hospital get better information technology support, and find more practical interventions to fight the epidemic.
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http://dx.doi.org/10.1007/s10916-021-01721-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894969PMC
February 2021

Big Data, Extracting Insights, Comprehension, and Analytics in Cardiology: An Overview.

J Healthc Eng 2021 30;2021:6635463. Epub 2021 Jan 30.

Department of Computer Science and Information Technology, University of Malakand, Chakdara, Pakistan.

Healthcare system facilitates the treatment of patients with the support of wearable, smart, and handheld devices, as well as many other devices. These devices are producing a huge bulk of data that need to be moulded for extracting meaningful insights from them for the useful use of researchers and practitioners. Various approaches, methods, and tools are in use for doing so and to extract meaningful information in the field of healthcare. This information is being used as evidence to further analyze the data for the early care of patient and to devise treatment. Early care and treatment can facilitate healthcare and the treatment of the patient and can have immense potentiality of dropping the care cost and quality refining of care and can decrease waste and chances of error. To facilitate healthcare in general and cardiology in specific, the proposed study presents an overview of the available literature associated with big data, its insights, and analytics. The presented report will help practitioners and researchers to devise new solutions for early care in healthcare and in cardiology.
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http://dx.doi.org/10.1155/2021/6635463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868142PMC
January 2021

TSC1 Suppresses Macrophage Necroptosis for the Control of Infection by Fungal Pathogen .

Immunohorizons 2021 Feb 17;5(2):90-101. Epub 2021 Feb 17.

The Center for Microbes, Development and Health, Chinese Academy of Sciences, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 200031 Shanghai, China;

is the most common, opportunistic human fungal pathogen whose complex interplay with the host innate immune system remains incompletely understood. In this study, we revealed that infection macrophages with triggers prominent cell death, which is largely attributed to the RIPK3/MLKL-mediated necroptosis. Our results further demonstrated that the TSC1-mTOR pathway plays a pivotal role in the control of macrophage necroptosis upon engaging the Dectin-1/2 and TLR-2/4 pathways through fungal components β-glucan/α-mannan or Sel1, respectively. Notably, the rapamycin-sensitive mTORC1 pathway, rather than the rapamycin-insensitive mTORC2 pathway, was responsible for elevated activation of RIPK1, RIPK3, and MLKL in TSC1-deficient macrophages. Following systemic infection with , mice with macrophage/neutrophil-specific deletion of () showed heightened fungal burden in multiple organs, such as the kidney, liver, and spleen, severe morbidity, and mortality. Notably, kidneys exhibited prominent cell death and concomitant loss of tissue-resident macrophages, which likely contributing to a dampened phagocytosis of fungal pathogens. Together, our data demonstrate a crucial role for the TSC1-mTOR pathway in the regulation of macrophage necroptosis and suggest that both Dectin- and TLRs-induced necroptosis may undermine the immune defense effector functions of these innate receptors during infection.
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http://dx.doi.org/10.4049/immunohorizons.2000093DOI Listing
February 2021

Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®.

NPJ Breast Cancer 2021 Feb 12;7(1):15. Epub 2021 Feb 12.

Clinical Trials and Statistics Unit (ICR-CTSU), Division of Clinical Studies, The Institute of Cancer Research, London, UK.

Multi-gene prognostic signatures including the Oncotype® DX Recurrence Score (RS), EndoPredict® (EP) and Prosigna® (Risk Of Recurrence, ROR) are widely used to predict the likelihood of distant recurrence in patients with oestrogen-receptor-positive (ER+), HER2-negative breast cancer. Here, we describe the development and validation of methods to recapitulate RS, EP and ROR scores from NanoString expression data. RNA was available from 107 tumours from postmenopausal women with early-stage, ER+, HER2- breast cancer from the translational Arimidex, Tamoxifen, Alone or in Combination study (TransATAC) where previously these signatures had been assessed with commercial methodology. Gene expression was measured using NanoString nCounter. For RS and EP, conversion factors to adjust for cross-platform variation were estimated using linear regression. For ROR, the steps to perform subgroup-specific normalisation of the gene expression data and calibration factors to calculate the 46-gene ROR score were assessed and verified. Training with bootstrapping (n = 59) was followed by validation (n = 48) using adjusted, research use only (RUO) NanoString-based algorithms. In the validation set, there was excellent concordance between the RUO scores and their commercial counterparts (r(RS) = 0.96, 95% CI 0.93-0.97 with level of agreement (LoA) of -7.69 to 8.12; r(EP) = 0.97, 95% CI 0.96-0.98 with LoA of -0.64 to 1.26 and r(ROR) = 0.97 (95% CI 0.94-0.98) with LoA of -8.65 to 10.54). There was also a strong agreement in risk stratification: (RS: κ = 0.86, p < 0.0001; EP: κ = 0.87, p < 0.0001; ROR: κ = 0.92, p < 0.001). In conclusion, the calibrated algorithms recapitulate the commercial RS and EP scores on individual biopsies and ROR scores on samples based on subgroup-centreing method using NanoString expression data.
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http://dx.doi.org/10.1038/s41523-021-00216-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881187PMC
February 2021

NG-Circos: next-generation Circos for data visualization and interpretation.

NAR Genom Bioinform 2020 Sep 3;2(3):lqaa069. Epub 2020 Sep 3.

Division of Computational Biomedicine, Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA 92697, USA.

Circos plots are widely used to display multi-dimensional next-generation genomic data, but existing implementations of Circos are not interactive with limited support of data types. Here, we developed next-generation Circos (NG-Circos), a flexible JavaScript-based circular genome visualization tool for designing highly interactive Circos plots using 21 functional modules with various data types. To our knowledge, NG-Circos is the most powerful software to construct interactive Circos plots. By supporting diverse data types in a dynamic browser interface, NG-Circos will accelerate the next-generation data visualization and interpretation, thus promoting the reproducible research in biomedical sciences and beyond. NG-Circos is available at https://wlcb.oit.uci.edu/NG-Circos and https://github.com/YaCui/NG-Circos.
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http://dx.doi.org/10.1093/nargab/lqaa069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671351PMC
September 2020

The clinical value of high-density lipoprotein in the evaluation of new coronavirus pneumonia.

Adv Clin Exp Med 2021 Feb;30(2):153-156

The First Affiliated Hospital of Nanchang University, China.

Background: The new coronavirus pneumonia (NCP, COVID-19) outbreak began in Wuhan in December 2019. The new coronavirus (2019 novel coronavirus (2019-nCoV)) can cause multiple organ damage, mainly to lung tissue, and induce inflammation in the body.

Objectives: To investigate the changes of high-density lipoprotein (HDL) level in patients with COVID-19 and assess its value in the evaluation and prognosis of this disease.

Material And Methods: This paper is a cross-sectional retrospective study. Eighty-six severe COVID-19 patients, 132 non-severe COVID-19 patients and 76 healthy individuals (control group) were recruited to measure triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) using enzyme-coupled colorimetry.

Results: The serum HDL-C level in COVID-19 group was 1.02 ±0.28 mmol/L which was significantly lower than in control group (1.52 ±0.55 mmol/L) (p < 0.05). In addition, the serum HDL-C level in severe COVID-19 group was 0.83 ±1.67 mmol/L, which was significantly lower than that in non-severe COVID-19 group (1.15 ±0.27 mmol/L) (p < 0.05).

Conclusions: Changes in HDL levels in patients with COVID-19 can reflect the severity of the disease and have a clinical significance in establishing the prognosis.
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http://dx.doi.org/10.17219/acem/130606DOI Listing
February 2021

Comparison of survival in non-metastatic inflammatory and other T4 breast cancers: a SEER population-based analysis.

BMC Cancer 2021 Feb 6;21(1):138. Epub 2021 Feb 6.

Department of breast disease, Henan Breast Cancer Center, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No.127, Dongming Road, Zhengzhou, 450008, China.

Background: Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored.

Methods: Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type.

Results: Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR-/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR-/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR-/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216-0.902; P = 0.025) and HR-/HER2- cohort (HR = 1.738; 95% CI: 1.192-2.534; P = 0.004).

Conclusions: Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR-/HER2+ subtype is associated with a better outcome, and HR-/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.
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http://dx.doi.org/10.1186/s12885-021-07855-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868017PMC
February 2021

Impacts of earthworm introduction and cadmium on microbial communities composition and function in soil.

Environ Toxicol Pharmacol 2021 Apr 2;83:103606. Epub 2021 Feb 2.

College of Life Science, Shaanxi Normal University, Xi'an, 710119, China. Electronic address:

Heavy metal contamination of soil has become a public concern. Earthworms are key players in the functioning and service of soil ecosystems, with comprehension of their introduction in the polluted soil offering new insights into the protection of soil resources. In the present study, we evaluated the effects of earthworm (Eisenia fetida) introduction and Cd (0, 10, 30, and 60 mg kg of Cd) exposure upon soil microbial community using 16S rRNA gene amplicon sequencing. Our research demonstrated that Gemmatimonadetes and Deinococcus-Thermus upregulated significantly, while Chryseolinea showed an obvious decreasing trend after earthworm introduction. In Cd contaminated soil, many genera exhibited a greater presence of Cd-dependent bacteria, namely Cd-tolerant bacteria such as Altererythrobacter and Luteimonas, and a decrease of sensitive bacteria, such as Amaricoccus and Haliangium. Moreover, functional prediction analysis of soil microbiota indicated that earthworm introduction and Cd exposure changed functional pathways of soil microorganisms. The results obtained in this study are beneficial for understanding soil microbial community impacted by earthworm, and for exploring Cd resistant or tolerant bacteria, with potentially significant findings for soil biodiversity and Cd bioremediation.
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http://dx.doi.org/10.1016/j.etap.2021.103606DOI Listing
April 2021

Adaptor Template Oligo-Mediated Sequencing (ATOM-Seq) is a new ultra-sensitive UMI-based NGS library preparation technology for use with cfDNA and cfRNA.

Sci Rep 2021 Feb 4;11(1):3138. Epub 2021 Feb 4.

GeneFirst Ltd, Building E5, Culham Science Centre, Abingdon, OX14 3DB, UK.

Liquid biopsy testing utilising Next Generation Sequencing (NGS) is rapidly moving towards clinical adoption for personalised oncology. However, before NGS can fulfil its potential any novel testing approach must identify ways of reducing errors, allowing separation of true low-frequency mutations from procedural artefacts, and be designed to improve upon current technologies. Popular NGS technologies typically utilise two DNA capture approaches; PCR and ligation, which have known limitations and seem to have reached a development plateau with only small, stepwise improvements being made. To maximise the ultimate utility of liquid biopsy testing we have developed a highly versatile approach to NGS: Adaptor Template Oligo Mediated Sequencing (ATOM-Seq). ATOM-Seq's strengths and versatility avoid the major limitations of both PCR- and ligation-based approaches. This technology is ligation free, simple, efficient, flexible, and streamlined, and it offers novel advantages that make it perfectly suited for use on highly challenging clinical material. Using reference and clinical materials, we demonstrate detection of known SNVs down to allele frequencies of 0.1% using as little as 20-25 ng of cfDNA, as well as the ability to detect fusions from RNA. We illustrate ATOM-Seq's suitability for clinical testing by showing high concordance rates between paired cfDNA and FFPE clinical samples.
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http://dx.doi.org/10.1038/s41598-021-82737-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862664PMC
February 2021

Mimicking Neurotransmitter Activity and Realizing Algebraic Arithmetic on Flexible Protein-Gated Oxide Neuromorphic Transistors.

ACS Appl Mater Interfaces 2021 Feb 3;13(6):7784-7791. Epub 2021 Feb 3.

School of Physical Science and Technology, Ningbo University, Ningbo, Zhejiang 315211, People's Republic of China.

Recently, flexible neuromorphic devices have attracted extensive attention for the construction of perception cognitive systems with the ultimate objective to achieve robust computation, efficient learning, and adaptability to evolutionary changes. In particular, the design of flexible neuromorphic devices with data processing and arithmetic capabilities is highly desirable for wearable cognitive platforms. Here, an albumen-based protein-gated flexible indium tin oxide (ITO) ionotronic neuromorphic transistor was proposed. First, the transistor demonstrates excellent mechanical robustness against bending stress. Moreover, spike-duration-dependent synaptic plasticity and spike-amplitude-dependent synaptic plasticity behaviors are not affected by bending stress. With the unique protonic gating behaviors, neurotransmission processes in biological synapses are emulated, exhibiting three characteristics in neurotransmitter release, including quantal release, stochastic release, and excitatory or inhibitory release. In addition, three types of spike-timing-dependent plasticity learning rules are mimicked on the ITO ionotronic neuromorphic transistor. Most interestingly, algebraic arithmetic operations, including addition, subtraction, multiplication, and division, are implemented on the protein gated neuromorphic transistor for the first time. The present work would open a promising biorealistic avenue to the scientific community to control and design wearable "green" cognitive platforms, with potential applications including but not limited to intelligent humanoid robots and replacement neuroprosthetics.
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http://dx.doi.org/10.1021/acsami.0c22047DOI Listing
February 2021

protoscoleces promotes proliferation and invasion of hepatocellular carcinoma cells.

Cytotechnology 2021 Feb 8;73(1):13-22. Epub 2020 Nov 8.

State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Xinjiang Medical University, Urumqi, 830054 Xinjiang People's Republic of China.

There may exist a connection between infection and cancer development. Here, it is aimed to investigate specific effects of protoscoleces (PSCs) on the proliferation and invasion capacities of hepatocellular carcinoma (HCC) cells in vitro and ex vitro. HepG2 cells were cultured with different quantities of PSCs in vitro. MTT analysis was used to evaluate effects of PSCs on the proliferation of HepG2 cells. Besides, scratch and transwell assays were respectively used for the detection of HepG2 cells migration and invasion capacities after co-culture with PSCs. Then, HepG2 cells were subcutaneously transplanted into nude mice with or without PSCs. From the 25th day of transplantation, the volume of subcutaneous lesions was measured every four days. At the 37th day, subcutaneous lesions were removed and their weight was evaluated. H&E staining was used for detecting basic pathological changes. HepG2 cells grew well without obvious morphological changes. Proliferation rate and migration capacity of HepG2 cells were higher in the co-culture group than the control group, which was closely associated with quantities of PSCs and co-culture time length. Moreover, HepG2 cells co-cultured with PSCs had stronger invasion ability than the control HepG2 cells. Importantly, there existed significant differences in the volume and weight of subcutaneous lesions after transplanting HepG2 cells with PSCs than the control group. HepG2 cells were also more pathologically heterogeneous in morphology after transplantation with PSCs. Thus, PSCs may promote proliferation and invasion of HCC cells.
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http://dx.doi.org/10.1007/s10616-020-00437-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7817750PMC
February 2021

BAFF, involved in B cell activation through the NF-κB pathway, is related to disease activity and bone destruction in rheumatoid arthritis.

Acta Pharmacol Sin 2021 Jan 22. Epub 2021 Jan 22.

Institute of Clinical Pharmacology, Anhui Medical University/Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry of China/Anti-inflammatory Immune Drugs Collaborative Innovation Center of Anhui Province, Hefei, 230032, China.

B cell activating factor of TNF family (BAFF) is a member of TNF ligand superfamily and plays a key role in B cell homeostasis, proliferation, maturation, and survival. In this study, we detected BAFF level, the expressions of BAFF receptors and important molecules in NF-κB pathway in rheumatoid arthritis (RA) patients and analyzed the correlation between BAFF level and clinical variables, laboratory parameters or X-ray scores in order to elucidate the roles of BAFF in RA. A total of 50 RA patients and 50 healthy controls (HCs) were enrolled. We showed that the serum BAFF level in RA patients was significantly higher than that of HCs, and the percentages of B cell subsets (CD19 B cells, CD19CD27 B cells, CD19CD20CD27 B cells, and CD19CD20CD27 B cells) in the serum of RA patients were significantly increased compared with those of HCs. The percentages of CD19BAFFR B cells, CD19 BCMA B cells, and CD19 TACI B cells in RA patients were significantly increased compared with those in HCs. The expression of important molecules in the NF-κB pathway (MKK3, MKK6, p-P38, p-P65, TRAF2, and p52) was significantly higher in RA patients than in HCs, but p100 level in RA patients was lower than that in HCs. The serum BAFF level was positively correlated with C-reactive protein, rheumatoid factor, disease activity score (in 28 joints), swollen joint counts, tender joint counts, and X-ray scores. When normal B cells were treated with BAFF in vitro, the percentages of the B cell subset and the expression of BAFF receptors were significantly upregulated. BAFF also promoted the expression of MKK3, MKK6, p-P38, p-P65, TRAF2, and p52. In conclusion, this study demonstrates that BAFF level is correlated with the disease activity and bone destruction of RA. BAFF is involved in the differentiation, proliferation, and activation of B cells in RA through NF-κB signaling pathway, suggesting that BAFF might be an ideal therapeutic target for RA.
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http://dx.doi.org/10.1038/s41401-020-00582-4DOI Listing
January 2021

Two immunogenic recombinant protein vaccine candidates showed disparate protective efficacy against Zika virus infection in rhesus macaques.

Vaccine 2021 Feb 13;39(6):915-925. Epub 2021 Jan 13.

Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address:

Zika virus (ZIKV) infection has caused major public health problems recently. To develop subunit vaccines for ZIKV, we have previously constructed recombinant ZIKV envelope protein domain III (EDIII), and the entire ectodomain (E80, which comprises EDI, EDII and EDIII), as vaccine candidates and showed both of them being immunogenic and protective in murine models. In this follow-up study, we compared these vaccine candidates in non-human primates. Both of them elicited neutralizing antibody responses, but only E80 immunization inhibited ZIKV infection in both peripheral blood and monkey tissues, whereas EDIII increased blood ZIKV RNA through possibly antibody-dependent enhancement. Further investigations revealed that the virion-binding antibody response in E80 immunized monkeys persisted longer and stronger than in EDIII immunized monkeys. These results demonstrate that E80 is superior to EDIII as a vaccine candidate, and that the magnitude, quality and durability of virion-binding neutralizing antibodies are correlates of protection.
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http://dx.doi.org/10.1016/j.vaccine.2020.12.077DOI Listing
February 2021