Publications by authors named "Xudong Zhang"

408 Publications

CD36 Signaling in Diabetic Cardiomyopathy.

Aging Dis 2021 Jun 1;12(3):826-840. Epub 2021 Jun 1.

Division of Cardiology, Tongji Hospital, Tongji Medical College and Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan, China.

Cluster of differentiation 36 (CD36), also referred to as scavenger receptor B2, has been shown to serve multiple functions in lipid metabolism, inflammatory signaling, oxidative stress, and energy reprogramming. As a scavenger receptor, CD36 interacts with various ligands, such as oxidized low-density lipoprotein (oxLDL), thrombospondin 1 (TSP-1), and fatty acid (FA), thereby activating specific downstream signaling pathways. Cardiac CD36 is mostly expressed on the surface of cardiomyocytes and endothelial cells. The pathophysiological process of diabetic cardiomyopathy (DCM) encompasses diverse metabolic abnormalities, such as enhanced transfer of cardiac myocyte sarcolemmal FA, increased levels of advanced glycation end-products, elevation in oxidative stress, impaired insulin signaling cascade, disturbance in calcium handling, and microvascular rarefaction which are closely related to CD36 signaling. This review presents a summary of the CD36 signaling pathway that acts mainly as a long-chain FA transporter in cardiac myocytes and functions as a receptor to bind to numerous ligands in endothelial cells. Finally, we summarize the recent basic research and clinical findings regarding CD36 signaling in DCM, suggesting a promising strategy to treat this condition.
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http://dx.doi.org/10.14336/AD.2020.1217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139204PMC
June 2021

Clinical analysis of patients with primary and secondary extranodal natural killer/T-cell lymphoma of central nervous system.

Hematol Oncol 2021 Jun 1. Epub 2021 Jun 1.

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Extranodal natural killer (NK)/T-cell lymphoma (NKTL) is a rare non-Hodgkin lymphoma that rarely arise exclusively in or metastasizes to the central nervous system (CNS). Globally, CNS involvement of NKTL heralds a serious prognosis and there is no standard treatment. 19 of 414 patients (4.59%) with ENKL followed were diagnosed with CNS involvement between 2006 and 2020. Two patients had primary CNS (PCNS) NKTL, and 17 patients had secondary CNS (SCNS) invasion. A total of 9 patients survived and 10 patients died. The median overall survival time was 55 months, and the median survival time after CNS invasion was 17 months. The 5-year cumulative survival probability was 45.7%. In conclusion, CNS risk evaluation and prophylaxis treatment can be carried out for patients with NK/T-cell lymphoma prognostic index risk group III/IV. In terms of treatment, systemic therapy based on methotrexate combined with radiotherapy and intrathecal chemotherapy can be selected.
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http://dx.doi.org/10.1002/hon.2894DOI Listing
June 2021

Origins and evolving functionalities of tRNA-derived small RNAs.

Trends Biochem Sci 2021 May 27. Epub 2021 May 27.

Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine, Reno, NV, USA. Electronic address:

Transfer RNA (tRNA)-derived small RNAs (tsRNAs) are among the most ancient small RNAs in all domains of life and are generated by the cleavage of tRNAs. Emerging studies have begun to reveal the versatile roles of tsRNAs in fundamental biological processes, including gene silencing, ribosome biogenesis, retrotransposition, and epigenetic inheritance, which are rooted in tsRNA sequence conservation, RNA modifications, and protein-binding abilities. We summarize the mechanisms of tsRNA biogenesis and the impact of RNA modifications, and propose how thinking of tsRNA functionality from an evolutionary perspective urges the expansion of tsRNA research into a wider spectrum, including cross-tissue/cross-species regulation and harnessing of the 'tsRNA code' for precision medicine.
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http://dx.doi.org/10.1016/j.tibs.2021.05.001DOI Listing
May 2021

Effects of freeze-thaw and chemical preconditioning on the consolidation properties and microstructure of landfill sludge.

Water Res 2021 May 15;200:117249. Epub 2021 May 15.

Shanghai Chengtou Wastewater Treatment Co., Ltd, Shanghai 201203, PR China. Electronic address:

At present, a large amount of landfill sludge(LS) has been accumulated all over the world. For environmental and engineering purposes, there is an urgent need for deep dewatering and volume reduction of LS. The deep dewatering of LS mainly uses the method of chemical preconditioning and mechanical dewatering, which is easy to cause environmental pollution and is not conducive to the subsequent resource treatment of LS. To find a more environmentally friendly and efficient method for deep dewatering of LS, an in-situ treatment method combining freeze-thaw and vacuum preloading was proposed. In this paper, based on the existing research, through compression consolidation test and MIP, SEM micro test, the consolidation properties and microstructure of LS after freeze-thaw and chemical preconditioning were studied, and the vacuum consolidation principle of different preconditioning was explored. The results show that: Both FeCl and freeze-thaw preconditioning can increase the permeability coefficient and consolidation coefficient by one to two orders of magnitude; After freeze-thaw preconditioning, the void ratio of sludge decreases and the permeability coefficient increases; Under low consolidation pressure, the mechanical properties of the two kinds of pretreated sludge changed significantly; The original sludge is mainly composed of small pores. After FeCl conditioning, the large pores and mesopores increased significantly, while the small pores decreased. After freeze-thaw, the large pores and mesopores increase greatly, while the small pores decrease greatly; The original sludge is in the form of a dispersive flocculent structure with many impurities. After freeze-thaw, the intercluster pores increase, showing a honeycomb structure. After FeCl conditioning, the sludge structure is more compact and uniform. The change of microstructure and consolidation characteristics of sludge after conditioning reflects the difference of two different preconditioning mechanisms.
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http://dx.doi.org/10.1016/j.watres.2021.117249DOI Listing
May 2021

Sodium caprylate wash during Protein A chromatography as an effective means for removing protease(s) responsible for target antibody fragmentation.

Protein Expr Purif 2021 May 20;186:105907. Epub 2021 May 20.

Technology and Process Development (TPD), WuXi Biologics, 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai, 200131, China. Electronic address:

For recombinant proteins produced in Chinese hamster ovary (CHO) cells, fragmentation is a common phenomenon that results in generation of product-related low-molecular-weight (LMW) species. Recently while purifying a bispecific antibody (bsAb), we observed that the target protein experienced cleavage at a couple of potential sites, leading to truncated products. Further studies suggest that the cleavage can likely be attributed to residual CHO cell protease activity. In order to maximally remove potential protease(s) that contribute fragmentation, we optimized Protein A chromatography by adding sodium caprylate (SC) to the wash buffer. Upon optimization, fragmentation of Protein A eluate happened to a much lesser degree as compared to that of eluate from unoptimized process, and the increased sample stability is in accordance with significantly reduced host cell protein (HCP) level. Taken together, the data suggest that SC wash during Protein A chromatography is an effective means for removing HCPs including endogenous protease(s) that are responsible for target antibody fragmentation.
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http://dx.doi.org/10.1016/j.pep.2021.105907DOI Listing
May 2021

Corrigendum to "Polar auxin transport May Be responsive to specific features of flavonoid structure" [Phytochemistry 185 (2021) 112702].

Phytochemistry 2021 May 18;188:112801. Epub 2021 May 18.

Germplasm Bank of Wild Species, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China. Electronic address:

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http://dx.doi.org/10.1016/j.phytochem.2021.112801DOI Listing
May 2021

A real-time loop-mediated isothermal amplification for detection of the wheat dwarf virus in wheat and the insect vector Psammotettix alienus.

Plant Dis 2021 May 18. Epub 2021 May 18.

Northwest A&F University, College of Plant Protection, State Key Laboratory of Crop Stress Biology for Arid Areas, Yangling, China;

Wheat dwarf virus (WDV, genus Mastrevirus, family Geminiviridae) is an economically important and widespread pathogen of cereal crops. It causes huge yield loss in wheat due to the unavailability of resistant varieties and rapid transmission by the vector leafhopper, Psammotettix alienus (Dahlb). To monitor and forecast this viral disease, an early diagnosis method is required for WDV detection in both infected plants and the virus vectors. In this study, we developed a real-time loop-mediated isothermal amplification (LAMP) assay for WDV detection. The positive sample could be detected within 28-32 min by following a simple and cost-effective procedure. The real-time LAMP assay showed a sensitivity of 2.7×105-6 copies/µL for detection and a high specificity for WDV amplification, with a similar accuracy to qPCR. Furthermore, a tube-closed dye method facilitates the inspection of the LAMP reaction and avoids cross contamination in the detection of the virus. This valuable detection assay could serve as an important tool for diagnosis and forecasting wheat dwarf disease intensity in the field.
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http://dx.doi.org/10.1094/PDIS-10-20-2279-REDOI Listing
May 2021

RIPK3 Suppresses the Progression of Spontaneous Intestinal Tumorigenesis.

Front Oncol 2021 30;11:664927. Epub 2021 Apr 30.

Laboratory of Inflammation and Molecular Pharmacology, Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences & Biomedical Research Institute, Hubei University of Medicine, Shiyan, China.

Receptor-interacting protein 3 (RIPK3), a member of the family of serine/threonine protein kinases, emerged as a critical regulator of necroptosis. Downregulated expression of RIPK3 is correlated with poor prognosis in multiple tumor types. Here, we show that RIPK3 is involved in the progression of spontaneous intestinal tumorigenesis. As a clinical correlate, reduced expression of RIPK3 is positively associated with histological grade, lymphatic metastasis and poor prognosis in CRC patients. RIPK3-deficient ( ) mice exhibit increased tumor formation in spontaneous intestinal tumorigenesis. tumors promote hyperactivation of IL-6/STAT3 signaling, which exacerbates proliferation and inhibits apoptosis. Blocking IL-6 signaling suppressed tumor formation and reduced STAT3 activation in mice. Thus, our results reveal that RIPK3 is a tumor suppressor in spontaneous intestinal tumorigenesis, and implicate targeting the IL-6/STAT3 signaling axis as a potential therapeutic strategy for intestinal tumor patients with reduced RIPK3.
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http://dx.doi.org/10.3389/fonc.2021.664927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120274PMC
April 2021

Bioorthogonal catalytic patch.

Nat Nanotechnol 2021 May 10. Epub 2021 May 10.

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P. R. China.

Bioorthogonal catalysis mediated by transition metals has inspired a new subfield of artificial chemistry complementary to enzymatic reactions, enabling the selective labelling of biomolecules or in situ synthesis of bioactive agents via non-natural processes. However, the effective deployment of bioorthogonal catalysis in vivo remains challenging, mired by the safety concerns of metal toxicity or complicated procedures to administer catalysts. Here, we describe a bioorthogonal catalytic device comprising a microneedle array patch integrated with Pd nanoparticles deposited on TiO nanosheets. This device is robust and removable, and can mediate the local conversion of caged substrates into their active states in high-level living systems. In particular, we show that such a patch can promote the activation of a prodrug at subcutaneous tumour sites, restoring its parent drug's therapeutic anticancer properties. This in situ applied device potentiates local treatment efficacy and eliminates off-target prodrug activation and dose-dependent side effects in healthy organs or distant tissues.
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http://dx.doi.org/10.1038/s41565-021-00910-7DOI Listing
May 2021

Ferroptosis as a mechanism to mediate p53 function in tumor radiosensitivity.

Oncogene 2021 May 29;40(20):3533-3547. Epub 2021 Apr 29.

Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Ferroptosis, a form of regulated cell death triggered by lipid peroxidation, was recently identified as an important mechanism in radiotherapy (RT)-mediated tumor suppression and radioresistance, although the exact genetic contexts in which to target ferroptosis in RT remains to be defined. p53 is the most commonly mutated gene in human cancers and a major effector to RT. Here, we identify ferroptosis as a critical mechanism to mediate p53 function in tumor radiosensitivity. Mechanistically, RT-mediated p53 activation antagonizes RT-induced SLC7A11 expression and represses glutathione synthesis, thereby promoting RT-induced lipid peroxidation and ferroptosis. p53 deficiency promotes radioresistance in cancer cells or tumors at least partly through SLC7A11-mediated ferroptosis inhibition. Ferroptosis inducers (FINs) that inhibit SLC7A11 exert significant radiosensitizing effects in tumor organoids and patient-derived xenografts with p53 mutation or deficiency. Finally, we show that RT-induced ferroptosis correlates with p53 activation and better clinical outcomes to RT in cancer patients. Together, our study uncovers a previously unappreciated role of ferroptosis in p53-mediated radiosensitization and suggest using FINs in combination with RT to treat p53-mutant cancers.
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http://dx.doi.org/10.1038/s41388-021-01790-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141034PMC
May 2021

Clinical study on acupuncture treatment of hypertension with hyperactivity of liver yang.

Medicine (Baltimore) 2021 Apr;100(17):e25668

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine.

Introduction: Hypertension can lead to different degrees complications of cardiovascular and cerebrovascular, and increase the risk of sudden death. Acupuncture has become a complementary alternative therapy for hypertension because of its antihypertensive and nontoxic side effects. However, there is still lack of evidence-based medicine evidence for an effective acupuncture antihypertensive prescription. The purpose of this study is to evaluate the effect of a special acupuncture prescription on hypertension with hyperactivity of liver yang.

Methods: In this randomized controlled trial, we will recruit 56 hypertensive patients with hyperactivity of liver yang. Then the patients will be randomly divided into control group and experimental group. The control group will be treated with western medicine, and the experimental group will be treated with medicine combined with acupuncture. The intervention will last 4 weeks. The indices will be collected before acupuncture, after acupuncture, and 2 weeks after acupuncture. The primary outcome will be 24-hour ambulatory blood pressure. The secondary outcomes will be clinic blood pressure, anxiety and depression score, and the syndrome score of hyperactivity of liver yang. The auxiliary indicators will be blood pressure load values and salt sensitivity risk rate. The exploratory indicator will be acupoint diagnosis. The safety evaluation indicator will be incidence of adverse events.

Discussion: The results of this study will provide favorable evidence for the efficacy and safety of acupuncture in reducing blood pressure, and explore the positive reaction acupoints which related to hypertension.
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http://dx.doi.org/10.1097/MD.0000000000025668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084090PMC
April 2021

Ibrutinib combined with venetoclax for the treatment of relapsed/refractory diffuse large B cell lymphoma.

Ann Hematol 2021 Jun 26;100(6):1509-1516. Epub 2021 Apr 26.

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, China.

Treatment outcomes of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) are far from satisfactory. Certain efficacy of ibrutinib has been observed in non-GCB subtype DLBCL patients. This study aimed to investigate the efficacy and safety of ibrutinib plus BCL2 inhibitor venetoclax in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression. Combinational therapy (ibrutinib 560mg/day; venetoclax started 1 week later, oral dose increased from 100 to 400mg/day in 3 weeks) was conducted, and one cycle was 4 weeks. Both drugs were stopped when disease progress or serious adverse reactions appear. The primary end-point was overall response rate (ORR) at two cycles. From December 2018 to July 2020, a total of 13 patients were treated with the combined therapy. Among them, eleven (84.6%) patients previously received at least two treatment regimens, eight (61.5%) patients were C-myc and BCL2 double expression. The ORR at two cycles was 61.5%, with 3 (23.1%) patients achieved complete remission (CR) and 5 (38.4%) patients achieved partial remission (PR). The ORR at four cycles and six cycles was 53.8% and 46.2%, respectively. The median duration of response was 11 months (range, 1.5-13.6 months). The median progression-free survival and overall survival were 5.6 months (range, 0.4-15.6) and 11.3 months (range, 2.8-17.2), respectively. The most common adverse event was grade 1/2 neutropenia (53.8%), and nonhematologic toxicities included Grade1/2 diarrhea (46.2%) and elevated liver enzymes (30.8%). Combined therapy of ibrutinib and venetoclax showed promising efficacy and synergistic effects in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression, and the toxicities were well-tolerated.
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http://dx.doi.org/10.1007/s00277-021-04535-7DOI Listing
June 2021

Genetic engineering cellular vesicles expressing CD64 as checkpoint antibody carrier for cancer immunotherapy.

Theranostics 2021 7;11(12):6033-6043. Epub 2021 Apr 7.

Department of Pharmacology, Molecular Cancer Research Center, School of Medicine, Sun Yat-Sen University, Guangzhou/Shenzhen, China.

Immune checkpoint blockade therapies, especially those targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) have achieved impressive clinical responses in multiple types of cancers. To optimize the therapeutic effect of the checkpoint antibodies, many strategies including targeting delivery, controlled release, and cellular synthesis have been developed. However, within these strategies, antibodies were attached to drug carriers by chemical bonding, which may affect the steric configuration and function of the antibodies. Herein, we prepared cluster of differentiation 64 (CD64), a natural catcher of the fragment crystalline (Fc) of monomeric immunoglobulin G (IgG), and over-expressed it on the cell membrane nanovesicles (NVs) as PD-L1 antibody delivery vehicle (CD64-NVs-aPD-L1), which was employed to disrupt the PD-1/PD-L1 immunosuppressive signal axis for boosting T cell dependent tumor elimination. Meanwhile, chemical immunomodulatory drug cyclophosphamide (CP) was also encapsulated in the vesicle (CD64-NVs-aPD-L1-CP), to simultaneously restrain the regulatory T cells (Tregs) and invigorate Ki67CD8 T cells, then further enhance their anti-tumor ability. : The cell membrane NVs overexpressing CD64 were incubated with PD-L1 antibody and chemotherapeutic agent CP to prepare CD64-NVs-aPD-L1-CP. The CD64-NVs-aPD-L1-CP could simultaneously interrupt the immunosuppressive effect of PD-L1 and decrease the inhibition of Tregs, leading to tumor growth suppression and survival time extension. Conclusion: CD64-NVs are charismatic carriers to achieve both checkpoint blockade and immunomodulatory drugs for combined cancer immunotherapy.
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http://dx.doi.org/10.7150/thno.48868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058713PMC
April 2021

CXCL13 promotes intestinal tumorigenesis through the activation of epithelial AKT signaling.

Cancer Lett 2021 Jul 22;511:1-14. Epub 2021 Apr 22.

Laboratory of Inflammation and Molecular Pharmacology, School of Basic Medical Sciences & Biomedical Research Institute, Hubei Key Laboratory of Embryonic Stem Cell Research, Hubei University of Medicine, Shiyan 442000, China. Electronic address:

The excessive release of proinflammatory chemokines promotes cell proliferation and tumor growth in colorectal cancer. However, their regulatory functions and molecular pathogenesis have not been well elucidated. Here, we observed the upregulation of chemokine (C-X-C motif) ligand 13 (CXCL13) in human colorectal cancers and mouse intestinal tumors. Both CXCL13 deficiency and blockade of CXCL13 signaling ameliorated disease progression. CXCL13 promoted intestinal tumorigenesis through the activation of the AKT signaling pathway in a C-X-C chemokine receptor type 5 (CXCR5)-dependent manner. Intestinal microbiota translocation drove CXCL13 production in dendritic cells through the activation of NF-κB signaling. Inhibition of microbiota translocation decreased CXCL13 production and ameliorated intestinal tumorigenesis. Together, the results of this study identify a role for the CXCL13-CXCR5 axis is involved in the crosstalk between chemokines and cell growth during the development of intestinal tumorigenesis, which also provides a therapeutic strategy for targeting CXCL13/CXCR5 in the future clinical treatment of intestinal tumors.
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http://dx.doi.org/10.1016/j.canlet.2021.04.012DOI Listing
July 2021

Concentrated small extracellular vesicles from menstrual blood-derived stromal cells improve intrauterine adhesion, a pre-clinical study in a rat model.

Nanoscale 2021 Apr 13;13(15):7334-7347. Epub 2021 Apr 13.

Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110022, China.

We previously reported that transplantation of menstrual blood-derived stromal cells (MenSCs) significantly improved fertility restoration in intrauterine adhesion (IUA). However, it is difficult to obtain menstrual blood samples in some severe IUA patients who have amenorrhea or oligomenorrhea. Thus, a safe and effective stem cell replacement therapy is necessary to promote endometrial regeneration. Recent studies demonstrated that the effects of MenSCs are partly mediated in a paracrine manner via small extracellular vesicles (sEVs). To explore this possibility, we performed a pre-clinical study to investigate whether concentrated MenSC-derived sEVs (MenSCs-sEVs) are sufficient to repair IUA and the mechanisms underlying their action. Rat IUA models were established by mechanical injury, followed by the administration of MenSCs or MenSCs-sEVs through intrauterine transplantation. Consistent with the efficacy of MenSCs, MenSCs-sEVs effectively recovered the morphology, promoted regeneration of the glands and angiogenesis, and reversed endometrial fibrosis in the IUA uterus. The endometrial receptivity and pregnancy outcome significantly improved after repeated MenSCs-sEVs transplantations. In addition, all rats in the MenSCs-sEVs group had no hematological or biochemical abnormalities. Three-dimensional fluorescence imaging suggested that MenSCs tended to migrate through the bloodstream, whereas MenSCs-sEVs had a better localized therapeutic effect. Moreover, MenSCs and MenSCs-sEVs inhibited the TGFβ1/SMAD3 pathway in the IUA endometrium, while promoting the phosphorylation of SMAD1/5/8 and ERK 1/2 and upregulating the expression of BMP7. Thus, MenSCs-sEVs safely and effectively enhanced endometrial restoration, suggesting a promising non-cellular therapy for endometrial regeneration and a key role in MenSC-mediated IUA treatment.
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http://dx.doi.org/10.1039/d0nr08942gDOI Listing
April 2021

Placental diseases associated with assisted reproductive technology.

Reprod Biol 2021 Jun 13;21(2):100505. Epub 2021 Apr 13.

Department of Obstetrics and Gynecology, Tangdu Hospital, Air Force Military Medical University, Xi'an, 710038, China.

The placenta develops from the outer trophoblastic layer following the differentiation of the fertilized ovum and is therefore more susceptible to epigenetic regulatory changes caused by environmental interventions and influences during assisted reproductive technology. Furthermore, the placenta regulates the development of the fetal heart, brain, kidneys, bones, and other tissues and organs [1]. Placental dysplasia leads to poor perinatal outcomes as well as long-term health risks later in life, including neurodevelopmental disorders, tumors, and adult metabolic syndrome [2,3]. In view of the decisive role of the placenta during intrauterine fetal development, Graham J. Burton, an expert in placentology from the University of Cambridge, formally proposed the theory of "placenta-derived chronic diseases" in 2018 based on embryonic-derived diseases [4]. In this review, we summarized the changes in placental morphology and structure, growth dynamics, imprinted and non-imprinted genes, and other aspects attributable to assisted reproduction technology. Our review provides a theoretical basis for further research on placental changes caused by assisted reproductive technology that are most strongly associated with an increased risk of neonatal long-term diseases.
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http://dx.doi.org/10.1016/j.repbio.2021.100505DOI Listing
June 2021

Propofol modulates the proliferation, invasion and migration of bladder cancer cells through the miR‑145‑5p/TOP2A axis.

Mol Med Rep 2021 Jun 13;23(6). Epub 2021 Apr 13.

Department of Anesthesiology, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610041, P.R. China.

Propofol‑based anesthesia has been reported to reduce the recurrence and metastasis of a number of cancer types following surgical resection. However, the effects of propofol in bladder cancer (BC) are yet to be fully elucidated. The aim of the present study was to investigate the functions of propofol in BC and their underlying mechanisms. In the study, the expression of microRNA (miR)‑145‑5p in BC tissues and cell lines was evaluated using reverse transcription‑quantitative PCR, and the effects of propofol on BC cells were determined using cell viability, wound healing and Transwell cell invasion assays, bioinformatics analysis, western blotting, immunohistochemistry and tumor xenograft models. It was found that propofol significantly suppressed the proliferation, migration and invasion of BC cells . In addition, propofol induced miR‑145‑5p expression in a time‑dependent manner, and miR‑145‑5p knockdown attenuated the inhibitory effects of propofol on the proliferation, migration and invasion of BC cells. Topoisomerase II α (TOP2A) was a direct target of miR‑145‑5p, and silencing TOP2A reversed the effects of miR‑145‑5p knockdown in propofol‑treated cells. Furthermore, propofol suppressed tumor xenograft growth, which was partially attenuated by miR‑145‑5p knockdown. The present study provided novel insight into the advantages of surgical intervention with propofol anesthesia in patients with BC.
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http://dx.doi.org/10.3892/mmr.2021.12078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060790PMC
June 2021

Psychometric properties of the Chinese Parent Version of the Autism Spectrum Rating Scale: Rasch analysis.

Autism 2021 Apr 12:13623613211004054. Epub 2021 Apr 12.

Children's Hospital of Fudan University, China.

Lay Abstract: The Autism Spectrum Rating Scale is a behavioural rating scale completed by parents and teachers that is useful for identifying children with an autism spectrum disorder. The development of a modified Autism Spectrum Rating Scale suitable for use in China is important for the identification of children in China with an autism spectrum disorder. In this study, we examined the Modified Chinese Autism Spectrum Rating Scale using a statistical technique known as Rasch analysis. Rasch analysis tests whether the questionnaire meets the standards for modern scientific measurement. We used Rasch analysis to examine data from 2013 children in China including 420 diagnosed with an autism spectrum disorder who had been rated by a parent or grandparent. After removing a small number of items (questions), the Modified Chinese Autism Spectrum Rating Scale met the stringent criteria for Rasch measurement. The availability of a reliable and precise tool for assessing behaviours characteristic of an autism spectrum disorder in Chinese children will improve the identification and diagnosis of autism spectrum disorder in China, thus enabling better provision of support services.
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http://dx.doi.org/10.1177/13623613211004054DOI Listing
April 2021

IRAK-M knockout promotes allergic airway inflammation, but not airway hyperresponsiveness, in house dust mite-induced experimental asthma model.

J Thorac Dis 2021 Mar;13(3):1413-1426

Departments of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Background: IL-1 receptor associated-kinase (IRAK)-M, expressed by airway epithelium and macrophages, was shown to regulate acute and chronic airway inflammation exhibiting a biphasic response in an OVA-based animal model. House dust mite (HDM) is a common real-life aeroallergen highly relevant to asthma pathogenesis. The role of IRAK-M in HDM-induced asthma remains unknown. This study was aimed to investigate the effect of IRAK-M on allergic airway inflammation induced by HDM using IRAK-M knockout (KO) mice and the potential underlying mechanisms.

Methods: IRAK-M KO and wild-type (WT) mice were sensitized and challenged with HDM. The differences in airway inflammation were evaluated 24 hours after the last challenge between the two genotypes of mice using a number of cellular and molecular biological techniques. mechanistic investigation was also involved.

Results: Lung expression of IRAK-M was significantly upregulated by HDM in the WT mice. Compared with the WT controls, HDM-treated IRAK-M KO mice showed exacerbated infiltration of inflammatory cells, particularly Th2 cells, in the airways and mucus overproduction, higher epithelial mediators IL-25, IL-33 and TSLP and Th2 cytokines in bronchoalveolar lavage (BAL) fluid. Lung IRAK-M KO macrophages expressed higher percentage of costimulatory molecules OX40L and CD 80 and exhibited enhanced antigen uptake. However, IRAK-M KO didn't impact the airway hyperreactivity (AHR) indirectly induced by HDM.

Conclusions: The findings indicate that IRAK-M protects allergic airway inflammation, not AHR, by modifying activation and antigen uptake of lung macrophages following HDM stimulation. Optimal regulation of IRAK-M might indicate an intriguing therapeutic avenue for allergic airway inflammation.
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http://dx.doi.org/10.21037/jtd-20-2133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024803PMC
March 2021

Structural features of five types of maize starch granule subgroups sorted by flow cytometry.

Food Chem 2021 Sep 22;356:129657. Epub 2021 Mar 22.

Key Laboratory of Biology and Genetic Improvement of Maize in Arid Area of Northwest Region, Ministry of Agriculture, College of Agronomy, Northwest A&F University, Yangling Shaanxi 712100, China. Electronic address:

Subgroups of starch granules from five maize phenotypes including waxy-, normal-, popcorn-, sweet corn- and high-amylose maize were sorted by flow cytometry (FC) utilizing the side scatter channel (SSC) and forward scatter channel (FSC). SSC and FSC mainly reflecting internal object complexity, and object size, respectively. Subgroups with higher FSC signal always showed higher SSC signal, indicating larger granules exhibited higher internal structural complexity. Wide-angle and small-angle X-ray scattering analysis showed that the subgroups showing high SSC signal intensity also had high lamellar scattering intensity, and low crystallinity. Vibrational transitions of bonds analyzed by Fourier Transform Infrared Spectroscopy (FT-IR) showed that the subgroups of maize starches, except sweet corn starch, with high SSC signal had high intensities at 1045 and 1022 cm. Hence, our data demonstrate that the structural complexity detected by the SSC signal is mainly associated with lamellar and crystalline features of starch granules.
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http://dx.doi.org/10.1016/j.foodchem.2021.129657DOI Listing
September 2021

PANDORA-seq expands the repertoire of regulatory small RNAs by overcoming RNA modifications.

Nat Cell Biol 2021 Apr 5;23(4):424-436. Epub 2021 Apr 5.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.

Although high-throughput RNA sequencing (RNA-seq) has greatly advanced small non-coding RNA (sncRNA) discovery, the currently widely used complementary DNA library construction protocol generates biased sequencing results. This is partially due to RNA modifications that interfere with adapter ligation and reverse transcription processes, which prevent the detection of sncRNAs bearing these modifications. Here, we present PANDORA-seq (panoramic RNA display by overcoming RNA modification aborted sequencing), employing a combinatorial enzymatic treatment to remove key RNA modifications that block adapter ligation and reverse transcription. PANDORA-seq identified abundant modified sncRNAs-mostly transfer RNA-derived small RNAs (tsRNAs) and ribosomal RNA-derived small RNAs (rsRNAs)-that were previously undetected, exhibiting tissue-specific expression across mouse brain, liver, spleen and sperm, as well as cell-specific expression across embryonic stem cells (ESCs) and HeLa cells. Using PANDORA-seq, we revealed unprecedented landscapes of microRNA, tsRNA and rsRNA dynamics during the generation of induced pluripotent stem cells. Importantly, tsRNAs and rsRNAs that are downregulated during somatic cell reprogramming impact cellular translation in ESCs, suggesting a role in lineage differentiation.
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http://dx.doi.org/10.1038/s41556-021-00652-7DOI Listing
April 2021

Improved lithium-ion battery performance by introducing oxygen-containing functional groups by plasma treatment.

Nanotechnology 2021 Apr 14;32(27). Epub 2021 Apr 14.

School of Physical Science and Technology, Lanzhou University, Lanzhou 730000, People's Republic of China.

Metal sulfides are often used as cathode materials for lithium-ion batteries (LIBs) owing to their high theoretical specific capacity; however, excessively fast capacity decay during charging/discharging and rapid shedding during cycling limits their practical application in batteries. In this study, we proposed a strategy using plasma treatment combined with the solvothermal method to prepare cobalt sulfide (CoS)-carbon nanofibers (CNFs) composite. The plasma treatment could introduce oxygen-containing polar groups and defects, which could improve the hydrophilicity of the CNFs for the growth of the CoS, thereby increasing the specific capacity of the composite electrode. The results show that the composite electrode present a high discharge specific capacity (839 mAh gat a current density of 100 mA g) and good cycle stability (the capacity retention rate almost 100% at 2000 mA gafter 500 cycles), attributing to the high conductivity of the CNFs. This study proves the application of plasma treatment and simple vulcanization method in high-performance LIBs.
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http://dx.doi.org/10.1088/1361-6528/abf37dDOI Listing
April 2021

Interleukin-6 reverses Adriamycin resistance in nasal NK/T-cell lymphoma via downregulation of ABCC4 and inactivation of the JAK2/STAT3/NF-κB/P65 pathway.

Environ Toxicol Pharmacol 2021 Jul 23;85:103639. Epub 2021 Mar 23.

Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, PR China. Electronic address:

Chemotherapy is generally effective for extranodal natural killer (NK)/T-cell lymphoma (ENKTCL), nasal type. Nevertheless, multidrug resistance (MDR) remains a key challenge in treating nasal NK/T-cell lymphoma. Interleukin-6 (IL-6) is reportedly an important regulator of MDR in many cancers, implicating a role of IL-6 in the chemotherapy response. However, the effects and mechanism of IL-6 in nasal NK/T-cell lymphoma remain unclear. Herein, we demonstrated that the IL-6 serum level was decreased in nasal NK/T-cell lymphoma patients compared to chronic rhinitis patients. Lower serum levels of IL-6 were closely correlated with Ki67 expression and patient survival. ATP-binding cassette (ABC) drug transporter ABCC4 in patients was abnormally upregulated. IL-6 significantly inhibited resistance to Adriamycin (ADM) in ADM-resistant SNK-6 cells (SNK-6/ADM). Moreover, IL-6 resulted in cell cycle arrest and led to apoptosis in SNK-6/ADM cells. Furthermore, IL-6 decreased ABCC4, p-JAK2, p-STAT3, and phospho-NF-κB p65 expression in SNK-6/ADM cells. IL-6 in combination with ADM inhibited tumor growth and increased the survival of SNK-6/ADM xenograft mice. In conclusion, our findings suggest that IL-6 can inhibit the upregulation of ABCC4 and inactivate the JAK2/STAT3/NF-κB/P65 pathway to sensitize NK/T-cell lymphoma to ADM, indicating that combination therapy with IL-6 and other chemotherapeutic drugs may be effective in reversing acquired resistance in nasal NK/T-cell lymphoma.
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http://dx.doi.org/10.1016/j.etap.2021.103639DOI Listing
July 2021

MLKL inhibits intestinal tumorigenesis by suppressing STAT3 signaling pathway.

Int J Biol Sci 2021 17;17(3):869-881. Epub 2021 Feb 17.

Laboratory of Inflammation and Molecular Pharmacology, Hubei Key Laboratory of Embryonic Stem Cell Research, School of Basic Medical Sciences & Biomedical Research Institute, Hubei University of Medicine, Shiyan 442000, China.

Mixed lineage kinase domain-like protein (MLKL) plays an important role in necroptosis, but the role and mechanism of MLKL in intestinal tumorigenesis remain unclear. Here, we found that hematopoietic- and nonhematopoietic-derived MLKL affected intestinal inflammation, but nonhematopoietic-derived MLKL primarily inhibited intestinal tumorigenesis. Loss of MLKL enhanced intestinal regeneration and the susceptibility to intestinal tumorigenesis in mice by hyperactivating the Janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) axis. Furthermore, MLKL deficiency increased interleukin-6 (IL-6) production in dendritic cells. Administration of anti-IL-6R antibody therapy reduced intestinal tumorigenesis in mice. Notably, low MLKL expression in human colorectal tumors, which enhanced STAT3 activation, was associated with decreased overall survival. Together, our results reveal that MLKL exhibits a suppressive effect during intestinal tumorigenesis by suppressing the IL-6/JAK2/STAT3 signals.
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http://dx.doi.org/10.7150/ijbs.56152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975698PMC
February 2021

Linc-KILH potentiates Notch1 signaling through inhibiting KRT19 phosphorylation and promotes the malignancy of hepatocellular carcinoma.

Int J Biol Sci 2021 8;17(3):768-780. Epub 2021 Feb 8.

The Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University, 29 XingLongXiang Road, Changzhou, Jiangsu 213000, P.R. China.

Long noncoding RNAs (LncRNAs) are emerging as crucial regulators in the pathophysiological process of various tumors, including HCC. Here, we identify a novel lncRNA Linc-KILH (KRT19 interacting long noncoding RNA in hepatocellular carcinoma), which is significantly up-regulated in HCC tissues and positively correlated with larger tumor size, severer microvascular invasion, more intrahepatic metastasis and decreased survival of HCC patients. Silence of Linc-KILH remarkably inhibited the proliferation and metastasis abilities of KRT19-positive HCC cells and . Mechanistically, Linc-KILH interacts with KRT19 and then inhibits the phosphorylation of KRT19 on Ser35, thereby, enhancing the translocation of KRT19 from cytoplasm to membrane in KRT19 positive HCC cells. Additionally, we validated that KRT19 interacts with β-catenin but not RAC1 in HCC cells. Linc-KILH enhanced the interaction between β-catenin and KRT19 in cytoplasm and promoted the nuclear translocation of β-catenin in HCC cells. Furthermore, Linc-KILH could enhance the promoting function of KRT19 on Notch1 signaling with the existence of KRT19 in HCC cells. Collectively, we revealed that Linc-KILH exerts a vital function in KRT19 positive HCC progression and may likely be developed into an effective therapeutic target for HCC.
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http://dx.doi.org/10.7150/ijbs.52279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975697PMC
February 2021

ARRB1 Drives Gallbladder Cancer Progression by Facilitating TAK1/MAPK Signaling Activation.

J Cancer 2021 30;12(7):1926-1935. Epub 2021 Jan 30.

Department of Hepato-biliary-pancreatic Surgery, The Affiliated Changzhou No. 2 People's Hospital of Nanjing Medical University, XingLong Road 29#, Changzhou, Jiangsu 213000, P.R. China.

Gallbladder carcinoma (GBC) is the most common malignancy of the biliary tract, with a dismal 5-year survival of 5%. Recently, ARRB1, as a molecular scaffold, has been proposed to participate in the progression of multiple malignancies. However, the effect and regulatory mechanisms of ARRB1 in GBC have not been investigated. Our study aimed to explore the biological functional status and the possible molecular mechanisms of ARRB1 with respect to GBC progression. The survey showed that human GBC tissues exhibited increased levels of ARRB1 compared with normal tissues, and the high expression of ARRB1 was associated with poor prognosis of GBC patients. A series of and functional experiments based on knockdown of ARRB1 uncovered that ARRB1 enhanced GBC cell proliferation, migration, and invasion. Furthermore, we reported that TAK1, a component of the TNF /MAPK pathway, is a vital downstream effector of ARRB1. In addition, siTAK1 could abolish the functional changes between ARRB1 overexpression GBC cells and control ones. Our data revealed that ARRB1 facilitated the carcinogenesis and development of GBC through TNF/TAK1/MAPK axis, suggesting that ARRB1 may be a promising biomarker and treatment target for GBC patients.
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http://dx.doi.org/10.7150/jca.53325DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974532PMC
January 2021

Highly Controllable Etchless Perovskite Microlasers Based on Bound States in the Continuum.

ACS Nano 2021 Apr 17;15(4):7386-7391. Epub 2021 Mar 17.

Ministry of Industry and Information Technology Key Lab of Micro-Nano Optoelectronic Information System, Shenzhen Graduate School, Harbin Institute of Technology, Shenzhen 518055, People's Republic of China.

Lead halide perovskites have been promising materials for lasing applications. Despite that a series of perovskite microlasers have been reported, their lasing modes are confined by either the as-grown morphology or the etched boundary. The first one is quite random and incompatible with integration, whereas the latter one strongly spoils the laser performances. Herein, we propose and experimentally demonstrate a robust and generic mechanism to realize well-controlled perovskite microlasers without the etching process. By patterning a one-dimensional polymer grating onto a perovskite film, we show that the symmetry-protected bound states in the continuum (BICs) can be formed in it. The intriguing properties of BICs including a widely spread mode profile and high factor, associated with the exceptional gain of perovskite, produce single-mode microlasers with high repeatability, controllability, directionality, and a polarization vortex. This mechanism can also be extended to two-dimensional nanostructures, enabling BIC lasers with different topological charges.
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http://dx.doi.org/10.1021/acsnano.1c00673DOI Listing
April 2021

Apatinib with etoposide capsules as a third- or further-line therapy for extensive-stage small cell lung cancer: an open-label, multicenter, single-arm phase II trial.

Transl Lung Cancer Res 2021 Feb;10(2):889-899

Department of Internal Medicine, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China.

Background: Patients with extensive-stage small-cell lung cancer (ES-SCLC) have a particularly poor prognosis. And the treatment options for patients with relapsed or refractory ES-SCLC are limited. Thus, we conducted an open-label, multicenter, single-arm phase II clinical trial to assess the efficacy and safety of apatinib plus etoposide capsules as the third- or further-line treatment in ES-SCLC patients.

Methods: Patients with ES-SCLC who experienced disease progression following 2 to 3 previous therapies from 11 medical centers in China were enrolled to receive apatinib (250 mg/d, continuously) and etoposide capsules (50 mg/d, on day 1-21, per 28 days). The treatment continued until disease progression, treatment intolerance, or death. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and safety.

Results: Fifty-six patients with relapsed or refractory ES-SCLC were enrolled from January 2018 to February 2020 and 53 of them were eventually included in the evaluation population. The median follow-up was 9.8 months. At the data cut-off time (March 5, 2020), 39 patients (74%) had died and 44 (83%) had progressed. The median PFS was 3.0 months (95% CI, 2.1-3.9) and the median OS was 5.0 months (95% CI, 3.6-6.4). No complete responses were seen. Eleven patients (21%) showed a best response of partial response and 37 (70%) patients achieved stable disease. The ORR was 20.8% (11/53), and the disease control rate (DCR) was 90.6% (48/53). The 6-month OS rate was 40.1% (95% CI, 26.2-54). After 12 months, the OS rate was 18.4% (95% CI, 4.7-32.1). Possible treatment-related grade III/IV adverse events included leukopenia [8 (15.1%)], neutropenia [7 (13.2%)], anemia [4 (7.4%)], and hand-foot syndrome [2 (3.8%)]. During the study, no mortality occurred as a consequence of treatment.

Conclusions: Apatinib combined with etoposide capsules exhibits efficacy and has an acceptable safety profile. It could be used as a later-line treatment for ES-SCLC patients who have been heavily pretreated with standard therapies. Further exploration of apatinib combined with etoposide capsules in phase III trials is warranted.
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http://dx.doi.org/10.21037/tlcr-20-1235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947412PMC
February 2021

Proteomics analysis of the hypothalamus in spontaneously hypertensive rats treated with twirling reinforcing manipulation, twirling reducing manipulation or electroacupuncture.

Exp Ther Med 2021 Apr 19;21(4):381. Epub 2021 Feb 19.

School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, P.R. China.

Hypertension is one of the primary risk factors for cardiovascular diseases. Numerous proteins serve a critical role in hypertension. Acupuncture has been widely used as a treatment for hypertension in China. The results of the current study suggested that electroacupuncture (EA), twirling reinforcing manipulation (TRFM) and twirling reducing manipulation (TRDM) may be useful in the treatment of hypertension. Additionally, proteome analysis of spontaneously hypertensive rats treated with EA, TRFM and TRDM was performed. There were 117 (EA group), 61 (TRFM group) and 86 (TRDM group) differentially expressed proteins (DEPs) identified in the respective experimental groups compared with the model group. Moreover, parallel reaction monitoring assays were used to validate the reliability of the DEPs. The majority of the results were consistent with previous proteomics results, in particular that for expression of neudesin neurotrophic factor (NENF). NENF may potentially represent an antihypertensive drug target.
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http://dx.doi.org/10.3892/etm.2021.9812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918484PMC
April 2021