Publications by authors named "Min Shi"

1,010 Publications

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Changes in epidemiological features of vaccine preventable infectious diseases among three eras of national vaccination strategies from 1953 to 2018 in Shanghai, China.

Lancet Reg Health West Pac 2021 Feb 23;7:100092. Epub 2021 Jan 23.

Xuhui District Center for Disease Control and Prevention, Shanghai 200237, China.

Background: Recurring outbreaks of infectious diseases highlight the importance of population vaccination strategies. We aimed to assess the impact of national vaccination strategies on vaccine-preventable infectious diseases (VPDs) in Shanghai, China and to identify vulnerable groups that may benefit from future vaccination policies.

Methods: Infectious disease data from 1953 to 2018 was obtained from Xuhui District Center for Disease Control and Prevention, Shanghai China. We used joinpoint regression to show incidence, mortality and fatality trends and to determine annual percent change in incidence of 12 VPDs among three eras of national immunization strategies: (1)1953-1977, (2)1978-2007, and(3)2008-2018.

Findings: Incidence, mortality, and fatality from VPDs have decreased drastically over the three eras, despite the inclusion of more diseases over time. Strikingly, the overall yearly incidence of VPDs shows an increasing trend from 2000 to 2018 in Shanghai (annual percentage changes, APC:7.7,  = 0.025). In the third era (2008-2018), the three VPDs with the highest incidence were varicella (80.2 cases/100,000), hand, foot, and mouth disease (HFMD) (73.6 cases/100,000), and hepatitis (43.5 cases/100,000). A significant upward trend was also observed in hepatitis (APC:24.9, <0.001), varicella (APC:5.9,  = 0.006), and HFMD (APC:11.8,  = 0.003) from 2008-2018. Hepatitis and tuberculosis are the only VPDs with fatality cases in this period.

Interpretation: Focus is needed in controlling adult hepatitis and tuberculosis, either by introducing adult booster vaccines or by research into more effective vaccines. Varicella and HFMD are on the rise, but vaccines for these are not included in national programs. Strategies funded by government agencies or encouraged by research incentives are needed for varicella and HFMD, such as two-dose and novel multi-valent vaccines, respectively.

Funding: Chinese Ministry of Education, Shanghai Municipal Government.
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http://dx.doi.org/10.1016/j.lanwpc.2021.100092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315356PMC
February 2021

Limited Expansion of Human Hepatocytes in FAH/RAG2-Deficient Swine.

Tissue Eng Part A 2021 Jul 26. Epub 2021 Jul 26.

Mayo Clinic Minnesota, 4352, Surgery, Rochester, Minnesota, United States;

Background: The mammalian liver's regenerative ability has led researchers to engineer animals as incubators for expansion of human hepatocytes. The expansion properties of human hepatocytes in immunodeficient mice are well known. However, little has been reported about larger animals that are more scalable and practical for clinical purposes. Therefore, we engineered immunodeficient swine to support expansion of human hepatocytes and identify barriers to their clinical application.

Methods: Immunodeficient swine were engineered by knockout of recombinase activating gene 2 (RAG2) and fumarylacetoacetate hydrolase (FAH). Immature human hepatocytes (ihHCs) were injected into fetal swine by intrauterine cell transplantation (IUCT) at day 40 of gestation. Human albumin was measured as a marker of engraftment. Cytotoxicity against ihHCs was measured in transplanted piglets and control swine.

Results: Higher levels of human albumin were detected in cord blood of newborn FAH/RAG2-deficient (FR) pigs compared to immunocompetent controls (196.26 ng/dL vs 39.29 ng/dL, p = 0.008), indicating successful engraftment of ihHC after IUCT and adaptive immunity in the fetus. Although rare hepatocytes staining positively for human albumin were observed, levels of human albumin did not rise after birth but declined suggesting rejection of xenografted ihHCs. Cytotoxicity against ihHCs increased after birth 3.8% (95% CI: [2.1%, 5.4%], p < 0.001) and correlated inversely to declining levels of human albumin (p = 2.1 x 10-5, R2 = 0.17). Circulating numbers of T-cells and B-cells were negligible in FR pigs. However, circulating natural killer (NK) cells exerted cytotoxicity against ihHCs. NK cell activity was lower in immunodeficient piglets after IUCT than naive controls (30.4% vs 40.1% (p = 0.011, 95% CI for difference [2.7%, 16.7%]).

Conclusion: Immature human hepatocytes successfully engrafted in FR swine after IUCT. NK cells were a significant barrier to expansion of hepatocytes. New approaches are needed to overcome this hurdle and allow large scale expansion of human hepatocytes in immunodeficient swine.
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http://dx.doi.org/10.1089/ten.TEA.2021.0057DOI Listing
July 2021

[A case of oncocytic carcinoma at the base of the tongue with cervical lymph node metastasis and literature review].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Aug;35(8):748-751

Oncocytic carcinoma of tongue is extremely rare. This paper reports a case of malignant transformation from oncocytic adenoma to oncocytic carcinoma. A 29-year-old man complained of pharyngeal bleeding and swallowing obstruction. The tumor at the base of the tongue was surgically removed and the pathological diagnosis was oncocytic adenoma. After 5 years, the patient found a tumor of the right neck and felt pharyngeal bleeding and swallowing obstruction again. The next year, he was treated with surgery, chemotherapy and radiotherapy, and was diagnosed as oncocytic carcinoma with cervical lymph node metastasis. The patient showed no sign of recurrence until 30 months after the second operation, when tumor of tongue was detected by electronic laryngoscope. Surgery, chemotherapy and radioactive seed implantation were adopted again. Up to now, the follow-up data showed no evidence of recurrence.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.08.016DOI Listing
August 2021

Flow Cytometric Evaluation of Surface and Cytoplasmic TRBC1 Expression in the Differential Diagnosis of Immature T-Cell Proliferations.

Am J Clin Pathol 2021 Jul 24. Epub 2021 Jul 24.

Division of Hematopathology, Department of Pathology and Laboratory Medicine, Mayo Clinic, Rochester, MN, USA.

Objectives: Flow cytometric detection of T-cell clonality is challenging, particularly in differential diagnosis of immature T-cell proliferations. Studies have shown utility of TRBC1, in conjunction with other T-cell markers, as reliable means to identify T-cell clonality by flow cytometry. One limitation of surface TRBC1 (sTRBC1) evaluation is it cannot be detected in surface CD3 (sCD3)-negative T cells, such as normal or abnormal immature T-cell precursors. Here, we assess surface and cytoplasmic TRBC1 expression patterns in the differential diagnosis of T-lymphoblastic leukemia/lymphoma (T-ALL) vs normal thymocyte expansions.

Methods: Forty-three samples containing T-ALL, thymoma, normal thymus, and/or indolent T-lymphoblastic proliferation (i-TLBP), were evaluated.

Results: All 24 cases with normal thymocytes or i-TLBPs revealed a characteristic and reproducible sCD3/sTRBC1 expression pattern indicative of polytypic T-cell maturation. In contrast, all 19 T-ALLs lacked this polytypic maturation pattern and were either completely negative for sCD3/sTRBC1 or showed a minor sCD3-positive subset with a monotypic TRBC1 expression pattern. Cytoplasmic TRBC1 evaluation in 9 T-ALLs demonstrated a monotypic intracellular TRBC1-positive (n = 4) or TRBC1-negative (n = 5) expression, indicative of clonality.

Conclusions: Our findings demonstrate flow cytometric evaluation of surface and cytoplasmic TRBC1 expression can aid detection of T-cell clonality and differential diagnosis of immature T-cell proliferations.
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http://dx.doi.org/10.1093/ajcp/aqab098DOI Listing
July 2021

Depression accelerates gastric cancer invasion and metastasis by inducing a neuroendocrine phenotype via the catecholamine/β -AR/MACC1 axis.

Cancer Commun (Lond) 2021 Jul 20. Epub 2021 Jul 20.

Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, P. R. China.

Background: Depression is a common, easily ignored, accompanied disease of gastric cancer (GC) patients and is often observed with elevated plasma catecholamine levels. Depression frequently promotes GC progression and leads to poor clinical outcomes; however, the molecular mechanisms underlying depression-induced GC progression remain poorly understood. We aimed to study the effects of depression on GC progression and explore possible mechanisms mediating the action of depression-associated catecholamines on GC.

Methods: Depression states of GC patients were graded using the Patient Health Questionnaire-9, and plasma catecholamine levels were examined by high performance liquid chromatography coupled with tandem mass spectrometry. Migrative and invasive GC cells were examined using transwell assays, and metastatic GC niches were imaged using bioluminescence technology in a depression mouse model established with chronic unpredictable mild stress. Mouse depression-like behaviors were assessed through sucrose preference, forced swimming, and tail suspension tests. Characteristics of the neuroendocrine phenotype were observed via RT-PCR, Western blotting, flow cytometry, and transmission electron microscopy.

Results: Fifty-one GC patients (age: 53.61 ± 1.79 years; cancer duration: 3.71 ± 0.33 months; depression duration: 2.37 ± 0.38 months; male-to-female ratio: 1.55:1) were enrolled in the study. Depression grade was significantly higher in GC patients showing higher plasma levels of catecholamines (epinephrine: P = 0.018; noradrenaline: P = 0.009), higher oncogene metastasis-associated in colon cancer-1 (MACC1) level (P = 0.018), and metastasis (P < 0.001). Further, depression-associated catecholamine specifically bound to the beta-2 adrenergic receptor (β -AR) and upregulated MACC1 expression, and thus promoting neuroendocrine phenotypic transformation through direct binding between MACC1 and synaptophysin. Eventually, the neuroendocrine phenotypic transformation accelerated GC invasion in vitro and metastasis in vivo. However, β -AR antagonist ICI-118,551 or MACC1 silencing effectively blocked the catecholamine-induced neuroendocrine phenotypic transformation and eliminated depression-enhanced GC migration and invasion. Moreover, β -AR blocking or MACC1 silencing prevented GC metastasis attributed to a neuroendocrine phenotype in a depression mouse model.

Conclusions: Catecholamine-induced neuroendocrine phenotypes of GC cells led to depression-accelerated GC invasion and metastasis via the β -AR/MACC1 axis, while β -AR antagonist or MACC1 silencing could reverse it, showing promising potential therapeutic strategies for improving the outcome of GC patients with comorbid depression.
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http://dx.doi.org/10.1002/cac2.12198DOI Listing
July 2021

Network meta-analysis on efficacy and safety of different anti-CGRP monoclonal antibody regimens for prophylaxis and treatment of episodic migraine.

Neurol Res 2021 Jul 19:1-18. Epub 2021 Jul 19.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, PR China.

Background: Currently, studies have shown that anti-CGRP monoclonal antibodies are effective drugs for the prophylaxis and treatment of episodic migraine. Therefore, for the first time, we classified and concluded 10 treatment regimens according to the different doses, drugs, routes of administration, and courses of treatment, so as to provide a reference for further clinical studies.

Methods: We studied relevant randomized controlled trials (RCTs) published before August 2020 on PubMed, Embase, Ovid MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials.

Results: Eleven RCTs involving 6397 patients were included in our analysis. Network meta-analysis results suggested that in the comparison of the average migraine days per month, Erenumab  (140 mg), Galcanezumab (120 mg, 240 mg), Fremanezumab (225 mg, 675 mg) were superior to placebo, Erenumab(7 mg), and the difference was statistically significant; Fremanezumab (225 mg, 675 mg) was superior to Erenumab (21 mg, 70 mg), and the difference was statistically significant; in the comparison of average medication days of acute migraine-specific drug per month, Erenumab (70 mg, 140 mg), Galcanezumab (120 mg, 240 mg), Fremanezumab (225 mg, 675 mg) was superior to placebo, and Erenumab (140 mg) and Galcanezumab (120 mg, 240 mg) were superior to Erenumab (70 mg), and the difference was statistically significant; there was no statistically significant difference in the average migraine days in the last month or in the medication days of acute migraine-specific drug.

Conclusion: Fremanezumab (225 mg) and Galcanezumab (120 mg) may be the best clinical protocol after a comprehensive assessment.
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http://dx.doi.org/10.1080/01616412.2021.1940672DOI Listing
July 2021

A visible-light mediated ring opening reaction of alkylidenecyclopropanes for the generation of homopropargyl radicals.

Chem Sci 2021 Jul 28;12(26):9088-9095. Epub 2021 May 28.

Key Laboratory for Advanced Materials and Institute of Fine Chemicals, Key Laboratory for Advanced Materials and Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry & Molecular Engineering, East China University of Science and Technology Meilong Road No. 130 Shanghai 200237 China.

Classical cyclopropylcarbinyl radical clock reactions have been widely applied to conduct mechanistic studies for probing radical processes for a long time; however, alkylidenecyclopropanes, which have a similar molecular structure to methylcyclopropanes, surprisingly have not yet attracted researcher's attention for similar ring opening radical clock processes. In recent years, photocatalytic NHPI ester activation chemistry has witnessed significant blooming developments and provided new synthetic routes for cross-coupling reactions. Herein, we wish to report a non-classical ring opening radical clock reaction using innovative NHPI esters bearing alkylidenecyclopropanes upon photoredox catalysis, providing a brand-new synthetic approach for the direct preparation of a variety of alkynyl derivatives. The potential synthetic utility of this protocol is demonstrated in the diverse transformations and facile synthesis of bioactive molecules or their derivatives and medicinal substances.
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http://dx.doi.org/10.1039/d1sc01889bDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261759PMC
July 2021

IOBR: Multi-Omics Immuno-Oncology Biological Research to Decode Tumor Microenvironment and Signatures.

Front Immunol 2021 2;12:687975. Epub 2021 Jul 2.

Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Recent advances in next-generation sequencing (NGS) technologies have triggered the rapid accumulation of publicly available multi-omics datasets. The application of integrated omics to explore robust signatures for clinical translation is increasingly emphasized, and this is attributed to the clinical success of immune checkpoint blockades in diverse malignancies. However, effective tools for comprehensively interpreting multi-omics data are still warranted to provide increased granularity into the intrinsic mechanism of oncogenesis and immunotherapeutic sensitivity. Therefore, we developed a computational tool for effective Immuno-Oncology Biological Research (IOBR), providing a comprehensive investigation of the estimation of reported or user-built signatures, TME deconvolution, and signature construction based on multi-omics data. Notably, IOBR offers batch analyses of these signatures and their correlations with clinical phenotypes, long non-coding RNA (lncRNA) profiling, genomic characteristics, and signatures generated from single-cell RNA sequencing (scRNA-seq) data in different cancer settings. Additionally, IOBR integrates multiple existing microenvironmental deconvolution methodologies and signature construction tools for convenient comparison and selection. Collectively, IOBR is a user-friendly tool for leveraging multi-omics data to facilitate immuno-oncology exploration and to unveil tumor-immune interactions and accelerating precision immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2021.687975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283787PMC
July 2021

CRIP1 cooperates with BRCA2 to drive the nuclear enrichment of RAD51 and to facilitate homologous repair upon DNA damage induced by chemotherapy.

Oncogene 2021 Jul 14. Epub 2021 Jul 14.

Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China.

Homologous recombination (HR) repair is an important determinant of chemosensitivity. However, the mechanisms underlying HR regulation remain largely unknown. Cysteine-rich intestinal protein 1 (CRIP1) is a member of the LIM/double-zinc finger protein family and is overexpressed and associated with prognosis in several tumor types. However, to date, the functional role of CRIP1 in cancer biology is poorly understood. Here we found that CRIP1 downregulation causes HR repair deficiency with concomitant increase in cell sensitivity to cisplatin, epirubicin, and the poly ADP-ribose polymerase (PARP) inhibitor olaparib in gastric cancer cells. Mechanistically, upon DNA damage, CRIP1 is deubiquitinated and upregulated by activated AKT signaling. CRIP1, in turn, promotes nuclear enrichment of RAD51, which is a prerequisite step for HR commencement, by stabilizing BRCA2 to counteract FBXO5-targeted RAD51 degradation and by binding to the core domain of RAD51 (RAD51) in coordination with BRCA2, to facilitate nuclear export signal masking interactions between BRCA2 and RAD51. Moreover, through mass spectrometry screening, we found that KPNA4 is at least one of the carriers controlling the nucleo-cytoplasmic distribution of the CRIP1-BRCA2-RAD51 complex in response to chemotherapy. Consistent with these findings, RAD51 inhibitors block the CRIP1-mediated HR process, thereby restoring chemotherapy sensitivity of gastric cancer cells with high CRIP1 expression. Analysis of patient specimens revealed an abnormally high level of CRIP1 expression in GC tissues compared to that in the adjacent normal mucosa and a significant negative association between CRIP1 expression and survival time in patient cohorts with different types of solid tumors undergoing genotoxic treatments. In conclusion, our study suggests an essential function of CRIP1 in promoting HR repair and facilitating gastric cancer cell adaptation to genotoxic therapy.
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http://dx.doi.org/10.1038/s41388-021-01932-0DOI Listing
July 2021

Identification of KRAS G12V associated clonal neoantigens and immune microenvironment in long-term survival of pancreatic adenocarcinoma.

Cancer Immunol Immunother 2021 Jul 13. Epub 2021 Jul 13.

Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin er Road, Shanghai, 200025, China.

Objective: To investigate the molecular characteristics in tumor immune microenvironment that affect long-term survival of patients with pancreatic adenocarcinoma (PAAD).

Methods: The tumor related genetic features of a female PAAD patient (over 13-year survival) who suffered from multiple recurrences and metastases, and six operations over one decade were investigated deeply. Genomic features and immune microenvironment signatures of her primary lesion as well as six metastatic tumors at different time-points were characterized.

Results: High-frequency clonal neoantigenic mutations identified in these specimens revealed the significant associations between clonal neoantigens with her prognosis after each surgery. Meanwhile, the TCGA and ICGC databases were employed to analyse the function of KRAS G12V in pancreatic cancer.

Conclusions: The genomic analysis of clonal neoantigens combined with tumor immune microenvironment could promote the understandings of personalized prognostic evaluation and the stratification of resected PAAD individuals with better outcome.
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http://dx.doi.org/10.1007/s00262-021-03012-4DOI Listing
July 2021

Thermally-Induced Intramolecular [4+2] Cycloaddition of Allylamino- or Allyloxy-Tethered Alkylidenecyclopropanes.

Chem Asian J 2021 Jul 7. Epub 2021 Jul 7.

State Key Laboratory of Organometallic Chemistry, Center for Excellence Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai, 200032, P. R. China.

A thermally-induced intramolecular [4+2] cycloaddition reaction of allylamino- or allyloxy-tethered alkylidenecyclopropanes has been reported in this paper, giving a new protocol for the rapid construction of polycyclic skeleton molecules in moderate to excellent yields with a broad substrate scope. On the basis of control experiments and DFT calculations, we disclosed that the reaction proceeded through a [4+2] cycloaddition and trace of water assisted 1,3-H shift process to give the target product.
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http://dx.doi.org/10.1002/asia.202100635DOI Listing
July 2021

Dual targeting of MEK and PI3K effectively controls the proliferation of human EGFR-TKI resistant non-small cell lung carcinoma cell lines with different genetic backgrounds.

BMC Pulm Med 2021 Jul 1;21(1):208. Epub 2021 Jul 1.

Department of Respiratory and Critical Care Medicine, Second Medical Center of Chinese PLA General Hospital, No. 28 of Fuxing Street, Haidian District, Beijing, 100853, China.

Background: Molecular targeted therapy for non-small cell lung carcinoma (NSCLC) is restricted due to resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). This study evaluated the effects of dual targeting of MEK and PI3K in human EGFR-TKI resistant NSCLC cell lines.

Methods: EGFR-TKI resistant NSCLC cell lines H1975, H460, and A549, with different mutation and amplification status in EGFR, K-RAS, PIK3CA, and MET genes, were treated with a MEK162 (MEK inhibitor) and BKM120 (PI3K inhibitor) combination or a BIBW2992 (EGFR inhibitor) and ARQ197 (MET inhibitor) combination and assayed for cell proliferation, apoptosis, and cell cycle distribution.

Results: Dual targeting of MEK and PI3K efficiently inhibited the cell proliferation, induced apoptosis and the G0/G1 cell cycle, and decreased the phosphorylation of ERK1/2, AKT, S6, and 4E-BP1. H460 cells with K-RAS and PIK3CA mutation were most sensitive to MEK162 and BKM120 combinations. H1975 cells with EGFR and PIK3CA mutation and MET amplification were sensitive to BIBW2992 and ARQ197 combinations.

Conclusion: Dual targeting regulated the proliferation of EGFR-TKI-resistant NSCLC cells, especially mutants in K-RAS and PIK3CA that are promising for EGFR-TKI-resistant NSCLC therapeutics.
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http://dx.doi.org/10.1186/s12890-021-01571-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252311PMC
July 2021

Comparative Transcriptome Analysis Reveals Sex-Based Differences during the Development of the Adult Parasitic Wasp (Hymenoptera: Braconidae).

Genes (Basel) 2021 Jun 10;12(6). Epub 2021 Jun 10.

Institute of Insect Science, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China.

The endoparasitic wasp is an important biological agent for controlling the population of , a major pest of cruciferous crops worldwide. Though the genome of has recently been reported, molecular mechanisms associated with sexual development have not been comprehensively studied. Here, we combined PacBio Iso-Seq and Illumina RNA-Seq to perform genome-wide profiling of pharate adult and adult development of male and female . Taking advantage of Iso-Seq full-length reads, we identified 14,466 novel transcripts as well as 8770 lncRNAs, with many lncRNAs showing a sex- and stage-specific expression pattern. The differentially expressed gene (DEG) analyses showed 2125 stage-specific and 326 sex-specific expressed genes. We also found that 4819 genes showed 11,856 alternative splicing events through combining the Iso-Seq and RNA-Seq data. The results of comparative analyses showed that most genes were alternatively spliced across developmental stages, and alternative splicing (AS) events were more prevalent in females than in males. Furthermore, we identified six sex-determining genes in this parasitic wasp and verified their sex-specific alternative splicing profiles. Specifically, the characterization of and splicing between male and female implies a conserved regulation mechanism of sexual development in parasitic wasps.
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http://dx.doi.org/10.3390/genes12060896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228208PMC
June 2021

The Impacts of Urbanization and Dietary Knowledge on Seaweed Consumption in China.

Foods 2021 Jun 14;10(6). Epub 2021 Jun 14.

College of Economics and Management, Huazhong Agricultural University, No.1 Shizi Shan Street, Hongshan District, Wuhan 430070, China.

Edible seaweed, a nutrient-rich and sustainable food, has a long dietary history in China. To get a better understanding of the seaweed consumption of consumers in China, this study investigates the quantity and trend of seaweed consumption of Chinese residents and employs a Tobit model to examine the effects of urbanization and dietary knowledge on seaweed consumption among residents. The results show an increasing trend of household seaweed consumption in China, including both seaweeds consumed at home (SAH) and seaweeds consumed away from home (SAFH). Households in urban areas consumed more seaweeds on average than those in rural areas. Urbanization promotes total household seaweed consumption, including SAH and SAFH, whilst dietary knowledge has a significantly positive impact on total household seaweed consumption and SAH. The findings supplement empirical evidence on the seaweed consumption behavior of Chinese residents and have important policy implications for further promoting Chinese seaweeds consumption in the context of urbanization and increasing dietary knowledge.
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http://dx.doi.org/10.3390/foods10061373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231840PMC
June 2021

S100 Calcium Binding Protein A10, A Novel Oncogene, Promotes the Proliferation, Invasion, and Migration of Hepatocellular Carcinoma.

Front Genet 2021 11;12:695036. Epub 2021 Jun 11.

Department of Oncology, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Hepatocarcinogenesis is a highly complicated process that is promoted by a series of oncogenes. Our study aims to identify novel oncogenes promoting hepatocellular carcinoma (HCC) by bioinformatic analysis and experimental validation. Here, we reported that S100 calcium binding protein A10 (S100A10) was screened out as a potential novel oncogene in HCC by integrated analysis of OEP000321 dataset and the Cancer Genome Atlas (TCGA)-Liver-Cancer data. Furthermore, S100A10 was highly expressed in HCC samples and observably associated with patients' overall survival (OS). Overexpression of S100A10 in Hep3B and Huh-7 increased the cell proliferation, whereas downregulation of S100A10 in SK-Hep-1 and HepG2 cells reduced the cell viability to almost stop growing. tumor growth assays showed that S100A10-overexpressing Hep3B cells had a larger tumor size than control. Moreover, S100A10 overexpression promoted Hep3B cells migration and invasion, and S100A10 knockdown inhibited SK-Hep-1 cells migration and invasion, . In conclusion, it is demonstrated that S100A10 is a novel oncogene in HCC, indicating a possible novel therapeutic strategy of HCC.
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http://dx.doi.org/10.3389/fgene.2021.695036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226228PMC
June 2021

Correlation of autophagy-related genes for predicting clinical prognosis in colorectal cancer.

Biomark Med 2021 Jun 25;15(10):715-729. Epub 2021 Jun 25.

Laboratory Animal Science & Technology Center, Workstation of Academician, College of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine, 1688 Meiling Road, Nanchang, 330004, PR China.

Autophagy plays a controversial role in cancer. The role of autophagy-related genes (ARGs) in colorectal cancer (CRC) was evaluated based on publicly available data from The Cancer Genome Atlas and the Human Autophagy Database. After collecting CRC-related transcript and clinical data and a list of ARGs from public databases, the Wilcoxon test was used to identify the differentially expressed ARGs between CRC and paired normal tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were used to identify the major biological properties and pathways associated with these genes. Univariate Cox regression was used to identify the prognosis-associated ARGs, and a forest plot was used to visualize the results. Kaplan-Meier analysis of the 5-year survival rate was performed. Univariate and multivariate Cox analyses were used to verify the impact of the prognosis-associated ARGs. A total of 36 differentially expressed genes (16 upregulated and 20 downregulated in CRC) were obtained from among 206 ARGs. There were 53 enriched pathways, including the p53 signaling pathway, platinum drug resistance, apoptosis, EGFR tyrosine kinase inhibitor resistance and ErbB signaling pathway (p- and q-values <0.05). Kaplan-Meier analysis showed that the 5-year survival rate was 46.0% (95% CI: 0.335-0.631) and 76.0% (95% CI: 0.651-0.886) in the high- and low-risk groups, respectively. The high-risk patients had worse survival probability (p = 6.256 × 10). Independent-samples -tests revealed that  expression was higher in patients aged ≤65 than >65 (p = 0.022);  expression was higher in patients aged ≤65 than >65 (p = 7.31 × 10), higher in M1 than M0 (p = 0.042), higher in N1-3 than N0 (p = 0.002) and higher in stage III and IV than I and II (p = 0.042); risk score was higher in N1-3 than N0 (p = 0.001) and in stage III and IV than I and II (p = 0.002); and expression was higher in M1 than M0 (p = 0.002), higher in N1-3 than N0 (p = 2.059 × 10) and higher in stage III and IV than I and II (p = 2.299 × 10). There were no differences in risk score between males and females (p = 0.593), T1-2 and T3-4 (p = 0.082) or M0 and M1 (p = 0.072). Univariate and multivariate Cox analyses showed that was a lower-risk gene, while , ,  and  were high-risk genes. Certain ARGs are potential prognostic molecular markers of poor prognosis in CRC. Additionally, the p53 signaling pathway, platinum drug resistance, apoptosis, EGFR tyrosine kinase inhibitor resistance and ErbB signaling pathway may be critical pathways regulated by ARGs in CRC.
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http://dx.doi.org/10.2217/bmm-2020-0292DOI Listing
June 2021

Development and validation of risk and prognostic nomograms for bone metastases in Chinese advanced colorectal cancer patients.

Ann Transl Med 2021 May;9(10):875

Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background: Bone metastases (BM) from colorectal cancer (CRC) are often accompanied by extraosseous metastases, resulting in a dismal prognosis. The present study aimed to determine the risk factors for BM in metastatic CRC (mCRC) and the prognostic factors for CRC patients with BM.

Methods: The study was based on a training cohort of 214 mCRC patients (of which, 101 patients had BM) from our center, and a validation cohort of 511 mCRC patients (of which, 173 patients had BM) from another institute. Risk and prognostic nomograms for BM were developed using univariate and multivariate analyses. The goodness of fit, discrimination, and calibration performance of the nomograms were assessed by R, concordance statistics (C-statistics), and the calibration curve. The results were internally validated using bootstrap resampling in the training cohort, and externally validated in the validation cohort.

Results: The novel BM risk nomogram comprised seven variables [degree of tumor differentiation, N-stage, serum alkaline phosphatase (ALP), lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), liver metastasis, and lung metastasis]. It showed good performance, with an R of 0.447 and a C-statistic of 0.846 [95% confidence interval (CI), 0.793 to 0.898] in the training cohort, and an R of 0.325 and a C-statistic of 0.792 (95% CI, 0.750 to 0.834) in the validation cohort. The optimal cutoff value to identify individuals at low or high risk was 56% probability, with a sensitivity of 71.3% and a specificity of 89.4%. The prognostic nomogram included five factors (tumor differentiation, number of extra-BM organs, number of BM lesions, ALP, and LDH), and had an R of 0.284 and a C-statistic of 0.723 (95% CI, 0.657 to 0.789) in the training set. This nomogram was externally validated in the validation cohort, with an R of 0.182 and a C-statistic of 0.682 (95% CI, 0.638 to 0.726).

Conclusions: The developed and validated risk and prognostic nomograms showed good performance for predicting the occurrence of BM in mCRC as well as the prognosis of CRC patients with BM. The risk nomogram can be used as a cost-effective preliminary screening tool prior to bone scanning.
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http://dx.doi.org/10.21037/atm-21-2550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184451PMC
May 2021

PSC-MSC-Derived Exosomes Protect against Kidney Fibrosis and through the SIRT6/-Catenin Signaling Pathway.

Int J Stem Cells 2021 Jun 30. Epub 2021 Jun 30.

Department of Thoracic Surgery, Xi'an Chest Hospital, Xi'an, China.

Background And Objectives: Chronic kidney disease (CKD) has a major impact on the quality of life of patients, and renal fibrosis is a critical pathological change in the disease. It is very important to control the process of renal fibrosis to improve the quality of life of patients with CKD. The pathological mechanism of renal fibrosis is very complicated, and the current treatment strategy also has many flaws.

Methods And Results: To explore a better treatment, we collected exosomes from pluripotent stem cell (PSC)-derived mesenchymal stem cells (MSC) and verified their therapeutic effect on renal fibrosis through and experiments. In this study, we found that PSC-MSC-derived comes could prevent the epithelial differentiation of NRK-52E cells, and with increasing exosome concentrations, the effect was improved. Furthermore, PSC-MSC-derived exosomes could reduce the pathological process of renal fibrosis, reduce inflammatory reactions and improve renal function in UUO mice. Moreover, the protective effect of exosomes against renal fibrosis may be achieved by increasing the expression of SIRT6 and decreasing the expression of -catenin and its downstream products.

Conclusions: These findings suggest the possibility of PSC-MSC-derived exosomes as a new, effective therapeutic tool for kidney fibrosis.
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http://dx.doi.org/10.15283/ijsc20184DOI Listing
June 2021

A serpin (CvT-serpin15) of teratocytes contributes to microbial-resistance in Plutella xylostella during Cotesia vestalis parasitism.

Pest Manag Sci 2021 Jun 21. Epub 2021 Jun 21.

Institute of Insect Sciences, Zhejiang University, 866 Yuhangtang Road, 310058, Hangzhou, China.

Background: Parasitic wasps are important group of entomophagous insects for pest control. As parasitic wasps often lay eggs on or into their associated hosts, parasitoids evolve to utilize several factors including venom, polydnavirus (PDV) to alter host physiology for successful parasitism. Some taxa of endoparasitoids produce teratocytes, which are a type of cells that are released into host insects when wasp eggs hatch. Teratocytes display multifunction in parasitism such as host nutritional exploration, immune and developmental regulation, by secreting plenty of proteins into host hemocoel.

Results: A serpin (CvT-serpin15) secreted by teratocytes was characterized. QPCR results showed the expressional level of CvT-serpin15 was upregulated following bacterial challenges. Enzyme activity experiment indicated the recombinant CvT-serpin15 protein could interfere the growth of Gram-positive bacteria Staphylococcus aureus. The survival rate assay demonstrated CvT-serpin15 increased survival rate of P. xylostella infected by S. aureus.

Conclusion: CvT-serpin15 secreted by teratocytes would boost the host immune system when pathogens invade host hemocoel during parasitism, and ultimately protect the development of wasp larva from bacterial infection.
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http://dx.doi.org/10.1002/ps.6515DOI Listing
June 2021

Copper-Catalyzed Synthesis of Indolyl Benzo[]carbazoles and Their Photoluminescence Property.

Org Lett 2021 Jul 18;23(13):5133-5137. Epub 2021 Jun 18.

State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, University of Chinese Academy of Science, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China.

A copper-catalyzed cascade cyclization of dihydroisobenzofurans with indoles for the rapid construction of indoly benzo[]carbazoles has been reported, providing the desired products in moderate to good yields under mild conditions along with a broad substrate scope and good functional group tolerance. The photoluminescence property of these indoly benzo[]carbazoles has also been investigated.
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http://dx.doi.org/10.1021/acs.orglett.1c01659DOI Listing
July 2021

First Report of Leaf Spot Caused by Ramularia sphaeroidea on Vicia villosa var. glabrescens in China.

Plant Dis 2021 Jun 15. Epub 2021 Jun 15.

Lanzhou University, College of Pastoral Agriculture Science and Technology, No. 768, Jiayuguan West Road, Lanzhou, Gansu, China, 730020.

Hairy vetch is widely grown in southwestern China for green manure and forage. In December 2019, a leaf disease occurred on 80% plants of in an eight-hectare field in Qujing(N 25°28'12″, E 103°36'22″), Yunnan Province, China. The disease leaves had irregular, brown to dark brown leaf spots with white mold. Twenty diseased leaves from five plants were randomly collected from the field. The leaf samples were sterilized with 75% ethanol for 30 s and 1% NaClO for 75 s, rinsed three times with sterile distilled water, surface water removed with sterile filter paper, and placed onto potato dextrose agar (PDA) for culture at 20oC. The obtained fungal isolates were purified by transferring 1 to 2 mm hyphal tips onto fresh PDA plates and cultured under the same temperature condition. The isolates grew slowly, at a rate of 0.7 mm/d at 20℃ for 4 weeks. A diseased plant specimen (accession MHLZU19326) and three isolates (accessions YN1931401, YN1931402, and YN1931403) were deposited in the Mycological Herbarium of Lanzhou University (MHLZU). Conidia from the PDA cultures were hyaline, spherical, smooth, aseptate, and measured 2.13 to 3.67 × 4.56 to 5.77 μm (n = 50). Conidiophores were hyaline, smooth, and straight. DNA of purified isolates was extracted and the nuclear ribosomal internal transcribed spacer (ITS), , and genes were amplified and sequenced with primers ITS1/ITS4 (White et al. 1990), EF1-728F/EF2 (Carbone and Kohn 1999;O'Donnell et al. 1998), CylH3F/CylH3R (Crous et al. 2004), and gpd1/gpd2 (Berbee et al. 1999), respectively. DNA sequences of isolates YN1931401, YN1931402, and YN1931403 were deposited in GenBank for the ITS (accessions MW092181, MW332205, and MW332206), (MW448172 to MW448174), (MW448175 to MW448177), and (MW448178 to MW448180). These sequences had the highest similarities with sequences of Sacc. in GenBank, 99%(514∕516, 515∕517, and 514∕517 bp) for ITS, 99% (402∕403, 403∕405, and 405∕405bp) for , 99% (377∕378, 378∕378, and 376∕378bp) for , and 100% (558∕557, 557∕559 and 561∕565 bp) for . A phylogenetic tree generated with the sequences clustered the fungus closely with . Infection experiments were carried out with 50 plants of in 10 pots. A conidial suspension of 1. 0 × 106 conidia/ml with 0.01% Tween 80 was prepared by adding sterile distilled water to the YN1931401 culture and scraping with a sterile scalpel. The leaves of 25 healthy plants were sprayed with the conidial suspension, and those of the 25 control plants were sprayed with sterile water. All plants were covered with clear polyethylene bags for 3 days to maintain high humidity and then grown in a greenhouse at diurnal cycles of 18℃ for 18h with light and 22℃ for 6 h in dark. Ten days post-inoculation, the inoculated plants exhibited brown lesions similar to the symptoms observed in the field (Fig. 1-F), whereas no symptoms appeared on the control plants. The same fungus was re-isolated and identified as described above. has been reported on and in Ethiopia and Israel (Braun 1998), on various species including in California, the United States (Koike et al. 2004) and on in China (Zhang et al. 2006), but to our knowledge, this is the first report of this fungus causing leaf spot on in China.
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http://dx.doi.org/10.1094/PDIS-04-21-0862-PDNDOI Listing
June 2021

MiR-130a-3p Has Protective Effects in Alzheimer's Disease via Targeting DAPK1.

Am J Alzheimers Dis Other Demen 2021 Jan-Dec;36:15333175211020572

Affiliated Mental Health Center, Zhejiang University School of Medicine, Zhejiang, China.

The present study investigated the role and potential mechanisms of miR-130a-3p in AD. SH-SY5Y cells were treated with Aβ 1-42 to construct AD cell models. APP/PS1 mice were used for the animal experiments.  MiR-130a-3p was downregulated in Aβ-induced SH-SY5Y cells. Overexpression of miR-130a-3p attenuates Aβ induced SH-SY5Y cell apoptosis. Low miR-130a-3p expression was detected in the hippocampus tissues of AD mice. The Morris water maze (MWM) results indicated that miR-130a-3p upregulation reduced the escape latency time and increased the time of AD mice spent in the target quadrant. DAPK1 was the target gene of miR-130a-3p. High DAPK1 mRNA level was detected in Aβ treated PC 12 cells and in the hippocampus tissues of AD mice. It was concluded that overexpression of miR-130a-3p may attenuate Aβ-induced neurotoxicity and improve the cognitive function of AD mice via targeting DAPK1.
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http://dx.doi.org/10.1177/15333175211020572DOI Listing
June 2021

Comparative transcriptome analysis reveals a potential mechanism for host nutritional manipulation after parasitization by Leptopilina boulardi.

Comp Biochem Physiol Part D Genomics Proteomics 2021 Jun 7;39:100862. Epub 2021 Jun 7.

Institute of Insect Sciences, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China; Ministry of Agriculture Key Lab of Molecular Biology of Crop Pathogens and Insect Pests, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Biology of Crop Pathogens and Insects of Zhejiang Province, Zhejiang University, Hangzhou 310058, China. Electronic address:

Parasitoids have been extensively found to manipulate nutrient amounts of their hosts to benefit their own development and survival, but the underlying mechanisms are largely unknown. Leptopilina boulardi (Hymenoptera: Figitidae) is a larval-pupal endoparasitoid wasp of Drosophila melanogaster whose survival relies on the nutrients provided by its Drosophila host. Here, we used RNA-seq to compare the gene expression levels of the host midgut at 24 h and 48 h post L. boulardi parasitization. We obtained 95 and 191 differentially expressed genes (DEGs) in the parasitized host midgut at 24 h and 48 h post L. boulardi parasitization, respectively. A KEGG analysis revealed that several metabolic pathways were significantly enriched in the upregulated DEGs, and these pathways included "starch and sucrose metabolism" and "galactose metabolism". A functional annotation analysis showed that four classes of genes involved in carbohydrate digestion process had increased expression levels in the midgut post L.boulardi parasitization than nonparasitized groups: glucosidase, mannosidase, chitinase and amylase. Genes involved in protein digestion process were also found among the DEGs, and most of these genes, which belonged to the metallopeptidase and serine-type endopeptidase families, were found at higher expression levels in the parasitized host midgut comparing with nonparasitized hosts. Moreover, some immune genes, particularly those involved in the Toll and Imd pathways, also exhibited high expression levels after L.boulardi parasitization. Our study provides large-scale transcriptome data and identifies sets of DEGs between parasitized and nonparasitized host midgut tissues at 24 h and 48 h post L. boulardi parasitization. These resources help improve our understanding of how parasitoid infection affects the nutrient components in the hosts.
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http://dx.doi.org/10.1016/j.cbd.2021.100862DOI Listing
June 2021

Topology and Content Co-Alignment Graph Convolutional Learning.

IEEE Trans Neural Netw Learn Syst 2021 Jun 11;PP. Epub 2021 Jun 11.

In traditional graph neural networks (GNNs), graph convolutional learning is carried out through topology-driven recursive node content aggregation for network representation learning. In reality, network topology and node content each provide unique and important information, and they are not always consistent because of noise, irrelevance, or missing links between nodes. A pure topology-driven feature aggregation approach between unaligned neighborhoods may deteriorate learning from nodes with poor structure-content consistency, due to the propagation of incorrect messages over the whole network. Alternatively, in this brief, we advocate a co-alignment graph convolutional learning (CoGL) paradigm, by aligning topology and content networks to maximize consistency. Our theme is to enforce the learning from the topology network to be consistent with the content network while simultaneously optimizing the content network to comply with the topology for optimized representation learning. Given a network, CoGL first reconstructs a content network from node features then co-aligns the content network and the original network through a unified optimization goal with: 1) minimized content loss; 2) minimized classification loss; and 3) minimized adversarial loss. Experiments on six benchmarks demonstrate that CoGL achieves comparable and even better performance compared with existing state-of-the-art GNN models.
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http://dx.doi.org/10.1109/TNNLS.2021.3084125DOI Listing
June 2021

The Abnormal Functional Connectivity in the Locus Coeruleus-Norepinephrine System Associated With Anxiety Symptom in Chronic Insomnia Disorder.

Front Neurosci 2021 21;15:678465. Epub 2021 May 21.

Department of Neurology, The Third Affiliated Hospital of Anhui Medical University, Heifei, China.

Background: Mental syndromes such as anxiety and depression are common comorbidities in patients with chronic insomnia disorder (CID). The locus coeruleus noradrenergic (LC-NE) system is considered to be crucial for modulation of emotion and sleep/wake cycle. LC-NE system is also a critical mediator of the stress-induced anxiety. However, whether the LC-NE system contributes to the underlying mechanism linking insomnia and these comorbidities remain unclear. This study aimed to investigate the LC-NE system alterations in patients with insomnia and its relationship with depression and anxiety symptoms.

Materials And Methods: Seventy patients with CID and 63 matched good sleep control (GSC) subjects were recruited and underwent resting-state functional MRI scan. LC-NE functional network was constructed by using seed-based functional connectivity (FC) analysis. The alterations in LC-NE FC network in patients with CID and their clinical significance was explored.

Results: Compared with GSC group, the CID group showed decreased left LC-NE FC in the left inferior frontal gyrus, while they had increased LC-NE FC in the left supramarginal gyrus and the left middle occipital gyrus (MOG). For the right LC-NE FC network, decreased FC was found in left dorsal anterior cingulate cortex (dACC). Interesting, the increased LC-NE FC was located in sensory cortex, while decreased LC-NE FC was located in frontal control cortex. In addition, the FC between the left LC and left MOG was associated with the duration of the disease, while abnormal FC between right LC and left dACC was associated with the anxiety scores in patients with CID.

Conclusion: The present study found abnormal LC-NE functional network in patients with CID, and the altered LC-NE function in dACC was associated with anxiety symptoms in CID. The present study substantially extended our understanding of the neuropathological basis of CID and provided the potential treatment target for CID patients who also had anxiety.
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http://dx.doi.org/10.3389/fnins.2021.678465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175797PMC
May 2021

Interpreting sulfhemoglobin and methemoglobin in patients with cyanosis: An overview of patients with M-hemoglobin variants.

Int J Lab Hematol 2021 Jun 6. Epub 2021 Jun 6.

Division of Hematopathology, Mayo Clinic, Rochester, MN, USA.

Introduction: Methemoglobin (MetHb) and sulfhemoglobin (SHb) measurements are useful in the evaluation of cyanosis. When one or both values are elevated, additional analysis is important to establish the etiology of the disorder. Methemoglobinemia occurs from acquired or hereditary causes with diverse treatment considerations, while true sulfhemoglobinemia is only acquired and treatment is restricted to toxin removal. Some toxic exposures can result in a dual increase in MetHb and SHb. Hereditary conditions, such as M-Hemoglobin variants (M-Hbs), can result in increased MetHb and/or SHb values but are clinically compensated and do not require treatment if they are cyanotic but otherwise clinically well.

Methods: Herein, we report 53 hemoglobin variant cases that have associated MetHb and SHb levels measured by an adapted Evelyn-Malloy laboratory assay method.

Results: Our data indicate M-Hbs cause variable patterns of MetHb and SHb elevation in a fairly reproducible pattern for the particular variant. In particular, α globin chain M-Hbs can mimic acquired sulfhemoglobinemia due to an isolated increased SHb value.

Conclusion: If the patient appears clinically well other than cyanosis, M-Hbs should be considered early in the evaluation process to differentiate from acquired conditions to avoid unnecessary testing and treatment regimens and prompt genetic counseling.
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http://dx.doi.org/10.1111/ijlh.13581DOI Listing
June 2021

Development of a Sensitive Diagnostic Assay for Parkinson Disease Quantifying α-Synuclein-Containing Extracellular Vesicles.

Neurology 2021 05 23;96(18):e2332-e2345. Epub 2021 Mar 23.

From the Departments of Pathology (Z.H., T.S., P.A., D.S., M.B., L.S., K.B., T.K., C.P., M.S., J.Z.), Neurology (C.P.Z.), and Psychiatry and Behavioral Sciences (E.R.P.), University of Washington School of Medicine, Seattle; Department of Neurology (Z.H.), West China Medical School, Sichuan University, Chengdu; Department of Pathology (C.T., J.Z.), Central Laboratory (J.Z.), The First Affiliated Hospital and School of Medicine, and National Health and Disease Human Brain Tissue Resource Center (J.Z.), Zhejiang University, Hangzhou; Geriatric Research, Education, and Clinical Center (C.P.Z.) and Mental Illness Research, Education, and Clinical Centre (E.R.P.), Veterans Affairs Puget Sound Health Care System, Seattle, WA; Parkinson's Disease Research, Education, and Clinical Care Center (J.F.Q.), Portland VA Medical Center; Department of Neurology (J.F.Q.), Oregon Health and Science University, Portland; Department of Pathology (T.J.M.), Stanford University School of Medicine, Palo Alto, CA; and Department of Neurology (J.A.), St. Olav's Hospital, Trondheim, Norway.

Objective: To develop a reliable and fast assay to quantify the α-synuclein (α-syn)-containing extracellular vesicles (EVs) in CSF and to assess their diagnostic potential for Parkinson disease (PD).

Methods: A cross-sectional, multicenter study was designed, including 170 patients with PD and 131 healthy controls (HCs) with a similar distribution of age and sex recruited from existing center studies at the University of Washington and Oregon Health and Science University. CSF EVs carrying α-syn or aggregated α-syn were quantified using antibodies against total or aggregated α-syn, respectively, and highly specific, sensitive, and rapid assays based on the novel Apogee nanoscale flow cytometry technology.

Results: No significant differences in the number and size distribution of total EVs between patients with PD and HCs in CSF were observed. When examining the total α-syn-positive and aggregated α-syn-positive EV subpopulations, the proportions of both among all detected CSF EVs were significantly lower in patients with PD compared to HCs ( < 0.0001). While each EV subpopulation showed better diagnostic sensitivity and specificity than total CSF α-syn measured directly with an immunoassay, a combination of the 2 EV subpopulations demonstrated a diagnostic accuracy that attained clinical relevance (area under curve 0.819, sensitivity 80%, specificity 71%).

Conclusion: Using newly established, sensitive nanoscale flow cytometry assays, we have demonstrated that total α-syn-positive and aggregated α-syn-positive EVs in CSF may serve as a helpful tool in PD diagnosis.

Classification Of Evidence: This study provides Class III evidence that total and aggregated α-syn-positive EVs in CSF identify patients with PD.
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http://dx.doi.org/10.1212/WNL.0000000000011853DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166433PMC
May 2021

Tumor Exosomes Reprogrammed by Low pH Are Efficient Targeting Vehicles for Smart Drug Delivery and Personalized Therapy against their Homologous Tumor.

Adv Sci (Weinh) 2021 05 16;8(10):2002787. Epub 2021 Mar 16.

State Key Laboratory of Biochemical Engineering Institute of Process Engineering Chinese Academy of Sciences No. 1 Bei-Er-Tiao, Zhong-Guan-Cun, Haidian District Beijing 100190 P. R. China.

As membrane-bound extracellular vesicles, exosomes have targeting ability for specific cell types, and the cellular environment strongly impacts their content and uptake efficiency. Inspired by these natural properties, the impacts of various cellular stress conditions on the uptake efficiency of tumor iterated exosomes are evaluated, and low-pH treatment caused increased uptake efficiency and retained cell-type specificity is found. Lipidomics analyses and molecular dynamics simulations reveal a glycerolipid self-aggregation-based mechanism for the enhanced homologous uptake. Furthermore, these low-pH reprogrammed exosomes are developed into a smart drug delivery platform, which is capable of specifically targeting tumor cells and selectively releasing diverse chemodrugs in response to the exosome rupture by the near-infrared irradiance-triggered burst of reactive oxygen species. This platform exerts safe and enhanced antitumor effects demonstrated by multiple model mice experiments. These results open a new avenue to reprogram exosomes for smart drug delivery and potentially personalized therapy against their homologous tumor.
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http://dx.doi.org/10.1002/advs.202002787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132050PMC
May 2021

CD2 and CD7 are sensitive flow cytometry screening markers for T-lineage acute leukemia(s): a study of 465 acute leukemia cases.

Hum Pathol 2021 May 18;114:66-73. Epub 2021 May 18.

Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, MN, 55905, USA. Electronic address:

T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) is a rare acute leukemia that expresses cytoplasmic CD3 (cCD3) and frequently lacks surface CD3. Given that routine flow cytometric testing for cCD3 may not be feasible and cCD3 interpretation may be difficult, we investigate if surface CD2 and/or CD7 expression on blasts can be used by flow cytometry to screen for T-lineage acute leukemia. We retrospectively reviewed flow cytometric data from 233 acute leukemias (36 T-ALL/LBL, 8 mixed-phenotype acute leukemia T/myeloid, 80 acute myeloid leukemia, 97 B-ALL/LBL, 8 mixed-phenotype acute leukemia B/myeloid, and 4 acute undifferentiated leukemia cases). Uniform expression (≥75% of blasts) of CD2 and/or CD7 was seen in all 44 cCD3-positive cases but in only 11% (20/189) of cCD3-negative acute leukemias, thus demonstrating 100% sensitivity and 89% specificity in the identification of cCD3-positive (T-lineage) acute leukemia. To avoid selection bias, we prospectively studied 232 consecutive acute leukemias for which cCD3, CD2, and CD7 were automatically performed in all cases. Similar to the retrospective study, uniform expression of CD2 and/or CD7 on blasts showed 100% sensitivity and 88% specificity in the screening for cCD3-positive (T-lineage) acute leukemia. Therefore, acute leukemias with uniform expression of CD2 and/or CD7 warrant further testing for cCD3 to evaluate for T-lineage acute leukemia. Blasts that lack both uniform CD2 and CD7 expression do not require additional cCD3 testing. We propose that CD2 and CD7 could be utilized in a limited antibody flow cytometry panel as a sensitive, robust, and cost-effective way to screen for T-lineage acute leukemia.
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http://dx.doi.org/10.1016/j.humpath.2021.05.007DOI Listing
May 2021

Effect of different administration and dosage of dexmedetomidine in the reduction of emergence agitation in children: a meta-analysis of randomized controlled trials with sequential trial analysis.

Transl Pediatr 2021 Apr;10(4):929-957

Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Background: Beneficial effects of dexmedetomidine (DEX) against emergence agitation (EA) in children remain controversial. We performed a more comprehensive meta-analysis to evaluate the protective effect of different administration routes, timing, patterns, and doses of DEX on EA in children.

Methods: The randomized controlled trials about DEX preventing EA in children were searched in PubMed, Cochrane Library, Embase, and Web of Sciences up to October 7, 2020. The traditional meta-analysis and subgroup analysis were performed to study the influence of DEX on EA in children. The sequential trial analysis (TSA) further analyzed the pooled results to evaluate meta-analyses' robustness. Grading of recommendation, assessment, development, and evaluation (GRADE) was used to assess evidence quality.

Results: Sixty-seven studies with 5,688 pediatric patients were included. DEX significantly decreased EA in children compared to placebo [RR 0.29, 95% confidence intervals (CI): 0.25-0.34] and midazolam (RR 0.34, 95% CI: 0.25-0.45), with firm evidence from TSA. Notably, using DEX significantly reduced severe EA incidence (RR 0.23, 95% CI: 0.16-0.32), with firm evidence by TSA and high quality of GRADE. Pre-specified subgroup analyses revealed firm and high-quality evidence for a reduction of EA, only if the perineural route administers DEX (RR 0.24, 95% CI: 0.14-0.41), as premedication (RR 0.27, 95% CI: 0.20-0.36), as continuous dosage (RR 0.25, 95% CI: 0.18-0.33), at high dose (RR 0.24, 95% CI: 0.18-0.31). The pooled results also showed that DEX reduced the incidence of PONV compared to placebo (RR 0.43, 95% CI: 0.33-0.55). Evidence for DEX's influence on other secondary outcomes (emergence time, time in PACU, rescue analgesia, hypotension, and bradycardia) is insufficient to draw any conclusion.

Conclusions: Our findings confirm the beneficial effects of DEX on EA, severe EA, and PONV in children. There was firm and high-quality evidence for the efficacy of DEX in preventing EA in children when perineural routes administered DEX, as premedication, as continuous dosage, and at a high dose. The best dose, route, patterns, and timing of DEX and influence on other outcomes call for further studies.
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http://dx.doi.org/10.21037/tp-21-105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107879PMC
April 2021
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