Publications by authors named "Ming Liu"

2,537 Publications

  • Page 1 of 1

Case Report: A Rare Case of Metachronous Multiple Primary Lung Cancers in a Patient With Successful Management by Switching From Anti-PD-1 Therapy to Anti-PD-L1 Therapy.

Front Immunol 2021 2;12:683202. Epub 2021 Jun 2.

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Without global standard diagnostic criteria, distinguishing multiple primary lung cancers (MPLCs) from intrapulmonary metastasis or histologic transformation has been a big challenge in clinical practice. Here, we described a rare case of metachronous adenocarcinoma and small cell lung cancer (SCLC) in a patient who developed drug resistance to pembrolizumab. Both DNA-sequencing and RNA-sequencing were performed on primary adenocarcinoma and resistant lesions. Through the comparison of primary adenocarcinoma and novel lesion mutation profiles, along with bioinformatic estimation of immune proportion by using RNA sequence data, we revealed the origin and tumor microenvironment of the two lesions. No shared mutations were detected between lung adenocarcinoma (LUAD) and SCLC from the same patient, suggesting these two lesions might be from separate primary lung cancers. Compared to LUAD, SCLC showed a relatively cold microenvironment, including negative PD-L1. The patient obtained durable clinical benefits upon treatment with atezolizumab, without experiencing immune-related adverse events. Disease progression should be monitored with prompt re-biopsy and molecular profiling to spot a potential histologic change and to shed light on therapeutic alternatives. The use of atezolizumab, either alone or in combination with other agents, may be a potential therapeutic strategy for patients with both LUAD and SCLC.
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http://dx.doi.org/10.3389/fimmu.2021.683202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8207139PMC
June 2021

A single-domain small protein Med-ORF10 regulates the production of antitumour agent medermycin in Streptomyces.

Microb Biotechnol 2021 Jun 17. Epub 2021 Jun 17.

Helmholtz International Lab for Anti-Infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, China.

Med-ORF10, a single-domain protein with unknown function encoded by a gene located in a gene cluster responsible for the biosynthesis of a novel antitumour antibiotic medermycin, shares high homology to a group of small proteins widely distributed in many aromatic polyketide antibiotic pathways. This group of proteins contain a nuclear transport factor-2 (NTF-2) domain and appear to undergo an evolutionary divergence in their functions. Gene knockout and interspecies complementation suggested that Med-ORF10 plays a regulatory role in medermycin biosynthetic pathway. Overexpression of med-ORF10 in its wild-type strain led to significant increase of medermycin production. It was also shown by qRT-PCR and Western blot that Med-ORF10 controls the expression of genes encoding tailoring enzymes involved in medermycin biosynthesis. Transcriptome analysis and qRT-PCR revealed that Med-ORF10 has pleiotropic effects on more targets. However, there is no similar conserved domain available in Med-ORF10 compared to those of mechanistically known regulatory proteins; meanwhile, no direct interaction between Med-ORF10 and its target promoter DNA was detected via gel shift assay. All these studies suggest that Med-ORF10 regulates medermycin biosynthesis probably via an indirect mode.
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http://dx.doi.org/10.1111/1751-7915.13834DOI Listing
June 2021

Fusion gene map of acute leukemia revealed by transcriptome sequencing of a consecutive cohort of 1000 cases in a single center.

Blood Cancer J 2021 Jun 16;11(6):112. Epub 2021 Jun 16.

Division of Pathology & Laboratory Medicine, Hebei Yanda Lu Daopei Hospital, 065201, Langfang, China.

Fusion genes (FGs) are important genetic abnormalities in acute leukemias, but their variety and occurrence in acute leukemias remain to be systematically described. Whole transcriptome sequencing (WTS) provides a powerful tool for analyzing FGs. Here we report the FG map revealed by WTS in a consecutive cohort of 1000 acute leukemia cases in a single center, including 539 acute myeloid leukemia (AML), 437 acute lymphoblastic leukemia (ALL), and 24 mixed-phenotype acute leukemia (MPAL) patients. Bioinformatic analysis identified 792 high-confidence in-frame fusion events (296 distinct fusions) which were classified into four tiers. Tier A (pathogenic), B (likely pathogenic), and C (uncertain significance) FGs were identified in 61.8% cases of the total cohort (59.7% in AML, 64.5% in ALL, and 63.6% in MPAL). FGs involving protein kinase, transcription factor, and epigenetic genes were detected in 10.7%, 48.5%, and 15.1% cases, respectively. A considerable amount of novel FGs (82 in AML, 88 in B-ALL, 13 in T-ALL, and 9 in MPAL) was identified. This comprehensively described real map of FGs in acute leukemia revealed multiple FGs with clinical relevance that have not been previously recognized. WTS is a valuable tool and should be widely used in the routine diagnostic workup of acute leukemia.
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http://dx.doi.org/10.1038/s41408-021-00504-5DOI Listing
June 2021

Transcriptional Start Site Coverage Analysis in Plasma Cell-Free DNA Reveals Disease Severity and Tissue Specificity of COVID-19 Patients.

Front Genet 2021 28;12:663098. Epub 2021 May 28.

BGI-Shenzhen, Shenzhen, China.

Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. A deep understanding of the variation of biological characteristics in severe COVID-19 patients is crucial for the detection of individuals at high risk of critical condition for the clinical management of the disease. Herein, by profiling the gene expression spectrum deduced from DNA coverage in regions surrounding transcriptional start site in plasma cell-free DNA (cfDNA) of COVID-19 patients, we deciphered the altered biological processes in the severe cases and demonstrated the feasibility of cfDNA in measuring the COVID-19 progression. The up- and downregulated genes in the plasma of severe patient were found to be closely related to the biological processes and functions affected by COVID-19 progression. More importantly, with the analysis of transcriptome data of blood cells and lung cells from control group and cases with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, we revealed that the upregulated genes were predominantly involved in the viral and antiviral activity in blood cells, reflecting the intense viral replication and the active reaction of immune system in the severe patients. Pathway analysis of downregulated genes in plasma DNA and lung cells also demonstrated the diminished adenosine triphosphate synthesis function in lung cells, which was evidenced to correlate with the severe COVID-19 symptoms, such as a cytokine storm and acute respiratory distress. Overall, this study revealed tissue involvement, provided insights into the mechanism of COVID-19 progression, and highlighted the utility of cfDNA as a noninvasive biomarker for disease severity inspections.
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http://dx.doi.org/10.3389/fgene.2021.663098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194351PMC
May 2021

Prediction of Hemorrhagic Transformation After Ischemic Stroke: Development and Validation Study of a Novel Multi-biomarker Model.

Front Aging Neurosci 2021 28;13:667934. Epub 2021 May 28.

Department of Neurology, Center of Cerebrovascular Diseases, West China Hospital, Sichuan University, Chengdu, China.

: We aimed to develop and validate a novel multi-biomarker model for predicting hemorrhagic transformation (HT) risk after acute ischemic stroke (AIS). : We prospectively included patients with AIS admitted within 24 h of stroke from January 1st 2016 to January 31st 2019. A panel of 17 circulating biomarkers was measured and analyzed in this cohort. We assessed the ability of individual circulating biomarkers and the combination of multiple biomarkers to predict any HT, symptomatic HT (sHT) and parenchymal hematoma (PH) after AIS. The strategy of multiple biomarkers in combination was then externally validated in an independent cohort of 288 Chinese patients. : A total of 1207 patients with AIS (727 males; mean age, 67.2 ± 13.9 years) were included as a derivation cohort, of whom 179 patients (14.8%) developed HT. The final multi-biomarker model included three biomarkers [platelets, neutrophil-to-lymphocyte ratios (NLR), and high-density lipoprotein (HDL)] from different pathways, showing a good performance for predicting HT in both the derivation cohort (c statistic = 0·64, 95% CI 0·60-0·69), and validation cohort (c statistic = 0·70, 95% CI 0·58-0·82). Adding these three biomarkers simultaneously to the basic model with conventional risk factors improved the ability of HT reclassification [net reclassification improvement (NRI) 65.6%, < 0.001], PH (NRI 64.7%, < 0.001), and sHT (NRI 71.3%, < 0.001). : This easily applied multi-biomarker model had a good performance for predicting HT in both the derivation and external validation cohorts. Incorporation of biomarkers into clinical decision making may help to identify patients at high risk of HT after AIS and warrants further consideration.
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http://dx.doi.org/10.3389/fnagi.2021.667934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193036PMC
May 2021

Intramuscular Expression of Plasmid-Encoded FVII-Fc Immunoconjugate for Tumor Immunotherapy by Targeting Tumoral Blood Vessels and Cells.

Front Oncol 2021 24;11:638591. Epub 2021 May 24.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China.

Tissue factor (TF) has been confirmed to be specifically expressed by vascular endothelial cells (VECs) in solid tumors and certain types of malignant tumor cells. Coagulation factor VII (FVII) can specifically bind to TF with high affinity, so the FVII-TF interaction provides an ideal target for tumor therapy. Expression of proteins in skeletal muscles is a simple and economical avenue for continuous production of therapeutic molecules. However, it is difficult to treat solid tumors till now due to the limited number of therapeutic proteins produced by the intramuscular gene expression system. Herein, we strived to explore whether anti-tumor effects can be achieved intramuscular delivery of a plasmid encoding a FVII-guided immunoconjugate (Icon) molecule by a previously established Pluronic L64/electropulse (L/E) technique. Our study exhibited several interesting outcomes. 1) The mouse light chain of FVII (mLFVII) molecule could guide red fluorescent protein (RFP) to accumulate predominantly at tumor sites in a TF-dependent manner. 2) Intramuscular expression of mLFVII-hFc (human IgG1 Fc) Icon could significantly inhibit the growth of both liver and lung cancers in nude mice, and the inhibition extent was proportional to the level of tumor-expressed TF. 3) The number of blood vessels and the amount of blood flow in tumors were significantly decreased in mLFVII-hFc Icon-treated mice. 4) This immunotherapy system did not display obvious side effects. Our study provided an efficient and economical system for tumor immunotherapy by targeting both blood vessels and tumor cells. It is also an open system for synergistic therapy by conveniently integrating other anticancer regimens.
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http://dx.doi.org/10.3389/fonc.2021.638591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181131PMC
May 2021

Brefeldin A Induces Apoptosis, Inhibits BCR-ABL Activation, and Triggers BCR-ABL Degradation in Chronic Myeloid Leukemia K562 Cells.

Anticancer Agents Med Chem 2021 Jun 8. Epub 2021 Jun 8.

Key Laboratory of Marine Drugs, The Ministry of Education of China, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by BCR-ABL oncoprotein. Tyrosine kinase inhibitors have been developed to inhibit the activity of BCR-ABL; however, drug resistance and side effect occur in clinic application. Therefore, it is urgent to find novel drugs for CML treatment. Under the guidance of cytotoxic activity, crude extracts of 55 fungal strains from the medicinal mangrove Acanthus ilicifolius were evaluated, and one potent cytotoxic natural compound, brefeldin A (BFA), was discovered from Penicillium sp. (HS-N-29).

Objective: This study was aimed to determine the cytotoxic activity of BFA and the effect on the activation and expression of BCR-ABL in K562 cells.

Method: We evaluated cytotoxic activity by MTT assay and soft agar clone assay and apoptosis and cell cycle distribution by Muse cell analyzer. The protein level of BCR-ABL and signaling molecules were detected by western blotting, and the mRNA level of BCR-ABL was determined by RT-PCR.

Results: BFA inhibited cell proliferation, induced G2/M cell cycle arrest, and stimulated cell apoptosis in K562 cells. Importantly, for the first time, we revealed that BFA inhibited the activation of BCR-ABL and consequently inhibited the activation of its downstream signaling molecules in K562 cells. Moreover, we found that BFA degraded BCR-ABL without affecting its transcription in K562 cells, and BFA-induced BCR-ABL degradation was related to caspase activation while not to autophagy or ubiquitinated proteasome degradation pathway.

Conclusion: Our present results indicate that BFA acts as a dual functional inhibitor and degrader of BCR-ABL, and BFA is a potential compound for chemotherapeutics to overcome CML.
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http://dx.doi.org/10.2174/1871520621666210608110435DOI Listing
June 2021

Identification of a novel plasmid-mediated carbapenemase-encoding gene in .

Antimicrob Agents Chemother 2021 Jun 7:AAC0020621. Epub 2021 Jun 7.

Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, P. R. China.

We characterized a carbapenem-resistant strain of shrimp origin with various experiments and bioinformatics analysis. A novel metallo-β-lactamase gene , conferring resistance to β-lactams including meropenem and cephalosporins, was identified on a plasmid-borne composite transposon IS-IS---IS capable of generating -bearing circular intermediate. IS was found disseminated on MDR pathogens, arousing the concern of further transmission of -bearing circular intermediate to clinical Enterobacterales via such insertion sequence, which warrants further investigations.
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http://dx.doi.org/10.1128/AAC.00206-21DOI Listing
June 2021

AIE-based nanoaggregate tracker: high-fidelity visualization of lysosomal movement and drug-escaping processes.

Chem Sci 2020 Aug 28;11(47):12755-12763. Epub 2020 Aug 28.

Shanghai Key Laboratory of Functional Materials Chemistry, Key Laboratory for Advanced Materials, Institute of Fine Chemicals, Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology Shanghai 200237 China

High-fidelity imaging and long-term visualization of lysosomes are crucial for their functional evaluation, related disease detection and active drug screening. However, commercial aggregation-caused quenching probes are not conducive to precise lysosomal imaging because of their inherent drawbacks, like easy diffusion, short emission and small Stokes shift, let alone their long-term tracing due to rapid photobleaching. Herein we report a novel aggregation-induced emission (AIE)-based TCM-PI nanoaggregate tracker for direct visualization of lysosomes based on the building block of tricyano-methylene-pyridine (TCM), wherein introduced piperazine (PI) groups behave as targeting units to lysosomes upon protonation, and the self-assembled nanostructure contributes to fast endocytosis for enhanced targeting ability as well as extended retention time for long-term imaging. The piperazine-stabilized TCM-PI nanoaggregate shifts the emission maximum to 677 nm in an aqueous environment, and falls within the desirable NIR region with a large Stokes shift of 162 nm, thereby greatly reducing biological fluorescent background interference. In contrast with the commercially available LysoTracker Red, the essential AIE characteristic of high photostability can guarantee three-dimensional high-fidelity tracing with low photobleaching, and little diffusion from lysosomes, and especially overcome the AIE bottleneck to target specificity. Consequently, the AIE-based nanoaggregate tracker successfully achieves the high-fidelity and long-term tracing of lysosomal movement and even monitors the drug-escaping process from lysosomes to cell nuclei, which provides a potential tool to benefit drug screening.
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http://dx.doi.org/10.1039/d0sc04156dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163247PMC
August 2020

Genomic and transcriptional alterations in first-line chemotherapy exert a potentially unfavorable influence on subsequent immunotherapy in NSCLC.

Theranostics 2021 13;11(14):7092-7109. Epub 2021 May 13.

Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, No. 507, Zhengmin Road, Yangpu District, Shanghai 200433, China.

Recent studies in non-small cell lung cancer (NSCLC) patients have demonstrated that first-line immunotherapy is associated with better therapeutic response than second-line treatment. So far, the mechanisms need to be explored. It prompted us to evaluate the association between first-line chemotherapy and subsequent immunotherapy in NSCLC as well as its underlying mechanisms at the genomic and transcriptomic level. We launched a prospective, observational clinical study, paired tumor biopsies before and after chemotherapy were collected from NSCLC patients without tyrosine kinase inhibitor (TKI)-related driver gene mutations. The analyses included genomic and transcriptional changes performed by next-generation sequencing (NGS)-based whole-exome sequencing (WES) and messager ribonucleic acid (mRNA) sequencing. Characteristic mutational alterations in 1574 genes were investigated based on mutational status, clinicopathological factors, and chemotherapy responses. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, neoantigen prediction and intratumoral heterogeneity evaluation were also performed. Samples and information from 32 NSCLC patients without TKI-related driver gene mutations were obtained. We found that the total number of single nucleotide variants (SNV)/insertion-deletion (INDEL) mutations did not change significantly after chemotherapy. The tumor mutation burden (TMB) decreased significantly after chemotherapy in smoking patients and the decreased TMB correlated with a better survival of smoking patients. The change in copy number variations (CNVs) exhibited a decreasing trend during chemotherapy. Subsequent analysis at mRNA level revealed a significant decrease in the expression levels of genes related to antigen processing and presentation as well as other factors relevant for response to immunotherapy. Pathway enrichment analysis confirmed that the immune-related signaling pathways or biological processes were decreased after first-line chemotherapy. Our study presents an explanation for the unsatisfactory results of immunotherapy when given after chemotherapy, and suggests that first-line chemotherapy is able to influence the tumor microenvironment and decrease the efficacy of subsequent immunotherapy. The study was registered at ClinicalTrials.gov, number NCT03764917, and has completed enrolment; patients are still in follow-up.
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http://dx.doi.org/10.7150/thno.58039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171101PMC
May 2021

Generation of an iPSC line (GWCMCi002-A) from an X-linked Alport syndrome patient with a hemizygous splicing mutation (NM_000495.4, c. 1517-1 G > T) in the COL4A5 gene.

Stem Cell Res 2021 May 11;53:102388. Epub 2021 May 11.

Nephrology Department, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China. Electronic address:

Pathogenic mutations in the COL4A5 gene are the main causes of X-Linked Alport Syndrome (XLAS). Here, to better understand the pathogenic mechanism of XLAS, we generated an iPSC line (GWCMCi002-A) from the peripheral blood mononuclear cells (PBMCs) of an 8-year-old male XLAS patient with a hemizygous splicing mutation (NM_000495.4, c. 1517-1 G > T) in the COL4A5 gene. This cell line will be beneficial for the study of the pathogenic mechanism of XLAS and the development of treatment strategies.
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http://dx.doi.org/10.1016/j.scr.2021.102388DOI Listing
May 2021

Comparison of the Efficacy of Minimally Invasive and Open Surgery on Children with Neuroblastoma: A Meta-Analysis.

J Laparoendosc Adv Surg Tech A 2021 Jun 1. Epub 2021 Jun 1.

Department of Pediatric Surgery, Fujian Province Maternal and Child Health Hospital, Fuzhou, China.

Evaluate the clinical efficacy and safety of minimally invasive surgery (MIS) and open surgery in the treatment of neuroblastoma (NB) in children by a meta-analysis. This is a meta-analysis. We searched for random or nonrandomized controlled study of MIS group and OPEN surgery group for the treatment of childhood NB included in PubMed, ClinicalTrials, EMBASE, and Cochrane library before January 31, 2020. Data extraction was performed in a standard format for the included studies, including tumor diameter, operation time, intraoperative bleeding, length of hospital stay (LOHS), complications, recurrence, and MYCN. Seven retrospective studies were finally included, with a total of 571 children, including 162 in MIS group and 409 in the OPEN surgery group. Compared with the OPEN surgery group, the MIS group had reduced intraoperative bleeding (mean difference [MD] = -12.72, 95% CI: -24.84 to -0.61,  < .05), and reduced l LOHS (MD = -3.35, 95% CI: -5.55 to -1.15,  < .05) and decreased postoperative recurrence (MD = 0.20, 95% CI: 0.05-0.75,  < .05). The differences between the groups were statistically significant. There was no significant difference between groups in tumor diameter (MD = -18.84, 95% CI: -48.12 to 10.43,  > .05), operation time (MD = -21.7, 95% CI: -97.52 to 54.13,  > .05), and MYCN results (odds ratio = 2.27, 95% CI: 0.56-9.18,  > .05). Preliminary evidence indicates that the treatment of NB with MIS has the advantages of less intraoperative bleeding, shorter LOHS, and less postoperative recurrence compared with open surgery.
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http://dx.doi.org/10.1089/lap.2020.0618DOI Listing
June 2021

A versatile nanoplatform based on multivariate porphyrinic metal-organic frameworks for catalytic cascade-enhanced photodynamic therapy.

J Mater Chem B 2021 Jun;9(23):4678-4689

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, China.

In recent years, the antitumor application of photodynamic therapy (PDT) has gained widespread interest in treating solid tumors. Due to the hypoxic environment in tumors, the major limit of PDT seems to be the source of oxygen. In this work, we attempted to relieve hypoxia and enhance photodynamic therapy, and therefore, designed and assembled a catalytic cascade-enhanced PDT multifunctional nanoplatform. The mentioned platform termed [email protected] is based on porphyrinic metal-organic framework (UIO) combination, which is simultaneously loaded by CaO2 NPs with polydopamine (PDA) and then the Pt raw material to further improve biocompatibility and efficiency. In a tumor microenvironment, CaO2 could react with water to generate calcium hydroxide and hydrogen peroxide, which was further decomposed by Pt nanoparticles to form oxygen, thereby facilitating the generation of cytotoxic singlet oxygen by photosensitizer TCPP under laser irradiation. Both in vitro and in vivo experiment results confirmed the excellent oxygen production capacity and enhanced PDT effect of [email protected] With guaranteed safety in PDT, the oxygen-supplying strategy might stimulate considerable interest in the development of various metal-organic materials with multifunctionality for tumor diagnosis and therapy.
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http://dx.doi.org/10.1039/d0tb02652bDOI Listing
June 2021

Potassium Fertilization Stimulates Sucrose-to-Starch Conversion and Root Formation in Sweet Potato ( (L.) Lam.).

Int J Mol Sci 2021 May 1;22(9). Epub 2021 May 1.

Institute of Integrative Plant Biology, School of Life Sciences, Jiangsu Normal University, Xuzhou 221116, China.

A field experiment was established to study sweet potato growth, starch dynamic accumulation, key enzymes and gene transcription in the sucrose-to-starch conversion and their relationships under six KO rates using Ningzishu 1 (sensitive to low-K) and Xushu 32 (tolerant to low-K). The results indicated that K application significantly improved the biomass accumulation of plant and storage root, although treatments at high levels of K, i.e., 300-375 kg KO ha, significantly decreased plant biomass and storage root yield. Compared with the no-K treatment, K application enhanced the biomass accumulation of plant and storage root by 3-47% and 13-45%, respectively, through promoting the biomass accumulation rate. Additionally, K application also enhanced the photosynthetic capacity of sweet potato. In this study, low stomatal conductance and net photosynthetic rate () accompanied with decreased intercellular CO concentration were observed in the no-K treatment at 35 DAT, indicating that was reduced mainly due to stomatal limitation; at 55 DAT, reduced in the no-K treatment was caused by non-stomatal factors. Compared with the no-K treatment, the content of sucrose, amylose and amylopectin decreased by 9-34%, 9-23% and 6-19%, respectively, but starch accumulation increased by 11-21% under K supply. The activities of sucrose synthetase (SuSy), adenosine-diphosphate-glucose pyrophosphorylase (AGPase), starch synthase (SSS) and the transcription of , , and were enhanced by K application and had positive relationships with starch accumulation. Therefore, K application promoted starch accumulation and storage root yield through regulating the activities and genes transcription of SuSy, AGPase and SSS in the sucrose-to-starch conversion.
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http://dx.doi.org/10.3390/ijms22094826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125193PMC
May 2021

Evaluation of Cell Surface Vimentin Positive Circulating Tumor Cells as a Diagnostic Biomarker for Lung Cancer.

Front Oncol 2021 14;11:672687. Epub 2021 May 14.

Department of Pulmonary and Critical Care Medicine, Guangzhou Institute of Respiratory Health, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Background: Circulating tumor cells (CTCs) represent a collection of heterogeneous cells. Studies have shown epithelial CTCs and folate receptor (FR) positive CTCs could be used as diagnostic biomarkers for lung cancer (LC). This study aimed to determine whether cell surface vimentin (CSV) positive CTCs could be used as a biomarker for LC as well.

Methods: 78 treatment-naïve non-small-cell lung cancer (NSCLC) patients, 21 patients with benign lung diseases (BLD) and 9 healthy donors (HD) were enrolled in this study. CTC detection was performed using CytoSorter mesenchymal CTC kit (CSV). The correlation between CSV positive CTCs (CSV-CTCs) and LC patients' clinicopathological characteristics would be evaluated, and diagnostic performances of CSV-CTCs and serum tumor markers for LC would be compared.

Results: CTC detection rates (average CTC count: range) in LC patients, patients with BLD and HD were 83.33% (2.47: 0-8), 47.62% (0.5: 0-3) and 0% (0: 0), respectively. CSV-CTCs could be used to differentiate LC patients from the patients with BLD and HD ( < 0.0001). CSV-CTCs were correlated with cancer stage, lymph node involvement and distant metastasis ( = 0.0062, 0.0014 and 0.0021, respectively). With a CTC cut-off value of 2, CSV-CTCs would have a sensitivity and specificity of 0.67 and 0.87, respectively, for diagnosing LC. CSV-CTC positive rates showed statistical differences among HD, BLD patients and LC patients at different cancer stages ( < 0.0001). Furthermore, CSV-CTC positive rates were positively correlated with tumor size, lymph node involvement and distant metastasis ( = 0.0163, 0.0196 and 0.03, respectively). CSV-CTCs had a better diagnostic performance than serum tumor makers, such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA125) and CA153.

Conclusion: When CTC cut-off is set to 2 CTCs per 7.5 mL of blood, CSV-CTCs can be considered as an acceptable biomarker for diagnosing LC with a sensitivity and specificity of 0.67 and 0.87, respectively.
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http://dx.doi.org/10.3389/fonc.2021.672687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162210PMC
May 2021

Creating porosity in a trianglimine macrocycle by heterochiral pairing.

Chem Commun (Camb) 2021 Jun 27;57(50):6141-6144. Epub 2021 May 27.

Materials Innovation Factory and Chemistry Department, University of Liverpool, Liverpool, L7 3NY, UK.

Macrocycles are usually non-porous or barely porous in the solid-state because of their small intrinsic cavity sizes and tendency to close-pack. Here, we use a heterochiral pairing strategy to introduce porosity in a trianglimine macrocycle, by co-crystallising two macrocycles with opposing chiralities. The stable racemic trianglimine crystal contains an interconnected pore network that has a Brunauer-Emmett-Teller (BET) surface area of 355 m g.
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http://dx.doi.org/10.1039/d1cc01650dDOI Listing
June 2021

Functional characterization of a loss-of-function mutant I324M of arginine vasopressin receptor 2 in X-linked nephrogenic diabetes insipidus.

Sci Rep 2021 May 26;11(1):11057. Epub 2021 May 26.

Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, 300052, China.

X-linked nephrogenic diabetes insipidus (X-linked NDI) is a rare inherited disease mainly caused by lost-of-function mutations in human AVPR2 gene encoding arginine vasopressin receptor 2 (V2R). Our focus of the current study is on exploration of the functional and biochemical properties of Ile324Met (I324M) mutation identified in a pedigree showing as typical recessive X-linked NDI. We demonstrated that I324M mutation interfered with the conformation of complex glycosylation of V2R. Moreover, almost all of the I324M-V2R failed to express on the cell surface due to being captured by the endoplasmic reticulum control system. We further examined the signaling activity of DDAVP-medicated cAMP and ERK1/2 pathways and the results revealed that the mutant receptor lost the ability in response to DDAVP stimulation contributed to the failure of accumulation of cAMP and phosphorylated ERK1/2. Based on the characteristics of molecular defects of I324M mutant, we selected two reagents (SR49059 and alvespimycin) to determine whether the functions of I324M-V2R can be restored and we found that both compounds can significantly "rescue" I324M mutation. Our findings may provide further insights for understanding the pathogenic mechanism of AVPR2 gene mutations and may offer some implications on development of promising treatments for patients with X-linked NDI.
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http://dx.doi.org/10.1038/s41598-021-90736-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154955PMC
May 2021

Letter to the Editor: T1a 0- to 2-cm Small Renal Masses.

Authors:
Boda Guo Ming Liu

J Natl Compr Canc Netw 2021 05;19(5):xxviii

aDepartment of Urology, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; and.

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http://dx.doi.org/10.6004/jnccn.2021.7020DOI Listing
May 2021

Identification of Key Genes With Differential Correlations in Lung Adenocarcinoma.

Front Cell Dev Biol 2021 5;9:675438. Epub 2021 May 5.

Tumor Biological Diagnosis and Treatment Center, The Third Affiliated Hospital of Soochow University, Changzhou, China.

Background: With the advent of large-scale molecular profiling, an increasing number of oncogenic drivers contributing to precise medicine and reshaping classification of lung adenocarcinoma (LUAD) have been identified. However, only a minority of patients archived improved outcome under current standard therapies because of the dynamic mutational spectrum, which required expanding susceptible gene libraries. Accumulating evidence has witnessed that understanding gene regulatory networks as well as their changing processes was helpful in identifying core genes which acted as master regulators during carcinogenesis. The present study aimed at identifying key genes with differential correlations between normal and tumor status.

Methods: Weighted gene co-expression network analysis (WGCNA) was employed to build a gene interaction network using the expression profile of LUAD from The Cancer Genome Atlas (TCGA). R package DiffCorr was implemented for the identification of differential correlations between tumor and adjacent normal tissues. STRING and Cytoscape were used for the construction and visualization of biological networks.

Results: A total of 176 modules were detected in the network, among which yellow and medium orchid modules showed the most significant associations with LUAD. Then genes in these two modules were further chosen to evaluate their differential correlations. Finally, dozens of novel genes with opposite correlations including ATP13A4-AS1, HIGD1B, DAP3, and ISG20L2 were identified. Further biological and survival analyses highlighted their potential values in the diagnosis and treatment of LUAD. Moreover, real-time qPCR confirmed the expression patterns of ATP13A4-AS1, HIGD1B, DAP3, and ISG20L2 in LUAD tissues and cell lines.

Conclusion: Our study provided new insights into the gene regulatory mechanisms during transition from normal to tumor, pioneering a network-based algorithm in the application of tumor etiology.
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http://dx.doi.org/10.3389/fcell.2021.675438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131847PMC
May 2021

Maternal gestational diabetes and childhood hyperlipidemia.

Diabet Med 2021 May 22:e14606. Epub 2021 May 22.

Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.

Aims: Aim of this study is to assess dyslipidemia risk between children exposed to maternal gestational diabetes mellitus (GDM) and those not exposed.

Methods: We recruited 1144 mother-child pairs (572 GDM and 572 non-GDM women matched by their offspring's age and sex). The age of offspring ranged from 3 to 9 years old. We used general linear models to compare mean values of different lipid profiles among children born to mothers with and without GDM. Logistic regression models were used to assess associations of maternal GDM with abnormal lipid profiles in offspring.

Results: After adjustment for maternal and children's characteristics, children born to mothers with GDM had lower mean values of high-density-lipoprotein (HDL) cholesterol (1.40 ± 0.01 vs. 1.50 ± 0.01; p < 0.001) and higher mean levels of triglycerides/HDL cholesterol ratio (0.37 ± 0.01 vs. 0.35 ± 0.01; p < 0.05) in comparison with their counterparts born to mothers without GDM. Multivariate-adjusted odds ratios among children exposed to mothers with GDM compared with the counterparts were 2.11 (95% confidence interval [CI 1.15-3.88]) for low HDL cholesterol and 1.35 (95% CI 1.00-1.81) for high triglycerides/HDL cholesterol ratio, respectively.

Conclusions: Maternal GDM was associated with an increased risk of hyperlipidemia in the offspring during early childhood aged from 3 to 9 years old.
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http://dx.doi.org/10.1111/dme.14606DOI Listing
May 2021

Dark Photon and Muon g-2 Inspired Inelastic Dark Matter Models at the High-Energy Intensity Frontier.

Phys Rev Lett 2021 May;126(18):181801

Los Alamos National Laboratory, Los Alamos, New Mexico 87545, USA.

We study hidden-sector particles at past (CERN-Hamburg-Amsterdam-Rome-Moscow Collaboration and NuCal), present (NA62, SeaQuest, and DarkQuest), and future (LongQuest) experiments at the high-energy intensity frontier. We focus on exploring the minimal vector portal and the next-to-minimal models in which the productions and decays are decoupled. These next-to-minimal models have mostly been devised to explain experimental anomalies while avoiding existing constraints. We demonstrate that proton fixed-target experiments provide one of the most powerful probes for the MeV to few GeV mass range of these models, using inelastic dark matter (iDM) as an example. We consider an iDM model with a small mass splitting that yields the observed dark matter relic abundance, and a scenario with a sizable mass splitting that can also explain the muon g-2 anomaly. We set strong limits based on the CERN-Hamburg-Amsterdam-Rome-Moscow Collaboration and NuCal experiments, which come close to excluding iDM as a full-abundance thermal dark matter candidate in the MeV to GeV mass range. We also make projections based on NA62, SeaQuest, and DarkQuest and update the constraints of the minimal dark photon parameter space. We find that NuCal sets the only existing constraint in ε∼10^{-8}-10^{-4} regime, reaching ∼800  MeV in dark photon mass due to the resonant enhancement of proton bremsstrahlung production. These studies also motivate LongQuest, a three-stage retooling of the SeaQuest experiment with short (≲5  m), medium (∼5  m), and long (≳35  m) baseline tracking stations and detectors as a multipurpose machine to explore new physics.
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http://dx.doi.org/10.1103/PhysRevLett.126.181801DOI Listing
May 2021

Comparison of changes in wound healing parameters following treatment with three topical wound care products using a laser wound model.

Am J Transl Res 2021 15;13(4):2644-2652. Epub 2021 Apr 15.

Department of Oral and Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine Shanghai 200011, China.

Purpose: This study intended to analyze the differences in the efficacy of three topical wound care products on wound healing in patients undergoing surgery under the laser wound model.

Method: A total of 130 patients in the department of dermatology enrolled for retrospective analysis. These patients were divided into group A (n=43, Zihua Shaoshang Ruangao), group B (n=43, Shengji Yuhong Gao), and group C (n=44, Shirun Shaoshang Gao), respectively, according to the type of wound care product administrated. The efficacy was compared during one month of treatment.

Results: There was little difference among groups A, B, and C in VAS score, FGF, EGF, and concentration of substance P (SP) at 1, 3, 5, 7, and 10 days after surgery (>0.05), and a significant difference in these parameters among different time points was observed for intra-group comparison (<0.05). There was no significant difference in the symptom scores at 1, 5, 10, 15, 20, 25, and 30 days after surgery among the three groups (>0.05), while there was statistically significant difference at different time points in the same group (<0.05). The wound healing rates at 10, 20, and 30 days after surgery were 25.58%, 65.12%, and 95.35% in group A, 20.93%, 67.44%, and 100.00% in group B and 25.00%, 59.09%, and 97.73% in group C respectively (>0.05). The patients' satisfaction rate towards the appearance was 95.35% in group A, 97.67% in group B, and 97.73% in group C (>0.05).

Conclusion: The three kinds of wound care products, namely Zihua Shaoshang Ruangao, Shengji Yuhong Gao and Shirun Shaoshang Gao, exhibited good efficacy on the wound care of patients after dermatologic surgery. The wounds could be improved quickly, and patients were highly satisfied with the new appearance of the wound. Clinically, wound care products can be selected according to the stock of products in the hospital and patients' preferences.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129399PMC
April 2021

Does the Internet Expand the Educational Gap Among Different Social Classes? The Protective Role of Future Orientation.

Front Psychol 2021 4;12:647351. Epub 2021 May 4.

Nanjing Zhonghua High School, Nanjing, China.

Amid the social background of China where the Internet has penetrated into every corner of an adolescent's life, we were concerned of the role of Internet usage in influencing the educational gap among social classes. We investigated the mediating role of Internet usage preference for entertainment in the relationship between the family socioeconomic status (SES) and the adolescent's academic achievement and explored the moderating role of future orientation in the relationship. A total of 614 junior high school students were recruited to complete a questionnaire survey, including questionnaires for family SES, Internet usage preference, and adolescent future orientation. The results showed that (1) the relationship between family SES and academic achievement was mediated by Internet usage preference for entertainment; (2) the indirect effect was moderated by future orientation, such that the negative association between family SES and Internet usage preference for entertainment was only indicated in adolescents with low future orientation; and (3) the direct association between family SES and Internet usage preference for entertainment was moderated by future orientation.
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http://dx.doi.org/10.3389/fpsyg.2021.647351DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129519PMC
May 2021

Attenuated serum vasoactive intestinal peptide concentrations are correlated with disease severity of non-traumatic osteonecrosis of femoral head.

J Orthop Surg Res 2021 May 20;16(1):325. Epub 2021 May 20.

Department of Orthopedics, Linyi People's Hospital, Jie Fang Road East, No.27, Linyi, 276003, Shandong Province, China.

Background And Objective: The neuropeptide vasoactive intestinal peptide is a 28-amino acid neuropeptide that has been shown to stimulate bone repair and angiogenesis. The purpose of this study was to explore the potential role of serum VIP concentration in osteonecrosis of femoral trauma (ONFH).

Methods: One hundred five patients diagnosed with non-traumatic ONFH and 103 healthy individuals were enrolled in our study. Serum VIP, tumor necrosis factor-α (TNF-α), interluekin-1 beta (IL-1β), and macrophage colony-stimulating factor (M-CSF) levels also were detected using the commercial ELISA kit. Radiographic progression was evaluated using FICAT classification. The clinical severity of ONFH was assessed by visual analog score (VAS) and Harris Hip Score (HHS). Receiver-operating characteristic (ROC) curve was performed to test the potential diagnostic value of VIP in radiographic progression.

Results: The serum VIP level of patients with non-traumatic ONFH was significantly lower than that of healthy controls. There was no significant difference between the alcohol group, the steroid-induction group, and the idiopathic group. Serum VIP levels were significantly higher in ONFH patients with femoral head pre-collapse stage than collapse stage. Serum VIP levels were significantly lower. FICAT 4 non-traumatic ONFH patients had significantly lower serum concentrations of VIP when compared with FICAT 3 and FICAT 2. Moreover, serum VIP levels were significantly lower in ONFH patients with FICAT 3 than FICAT 2. Serum VIP levels were negatively related to FICAT stage. In addition, serum VIP levels were negatively associated with VAS score and positively associated with HHS score. Last, we found serum VIP levels were negatively associated with serum TNF-α and IL-1β levels. ROC curve analysis indicated that decreased serum VIP could serve as a decent biomarker with regard to the diagnosis of radiographic progression.

Conclusion: Attenuated serum VIP concentrations are correlated with disease severity of non-traumatic ONFH. Decreased serum VIP may serve as a potential indicator of non-traumatic ONFH.
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http://dx.doi.org/10.1186/s13018-021-02486-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136083PMC
May 2021

Analysis of adversity quotient of nursing students in Macao: A cross-section and correlation study.

Int J Nurs Sci 2021 Apr 24;8(2):204-209. Epub 2021 Feb 24.

School of Health Science and Sports, Macao Polytechnic Institute, Macao SAR, China.

Objectives: To investigate the adversity quotient (AQ) of Macao undergraduate nursing students and analyse its influencing factors.

Methods: A cross-section design was used, and a convenience sample of nursing students ( = 158 valid) was selected from a tertiary institute in Macao. In addition to demographic questions, the Chinese versions of the Adversity Quotient Scale, the Emotional Intelligence (EI) Scale, the Simplified Coping Style Questionnaire and the Parenting Styles Scale were used to assess the students' characteristics.

Results: The average AQ score of the students was 116.72 ± 11.39. AQ scores were negatively correlated with coping-negative, and maternal style (excessive interference, excessive protection) ( = -0.332,  < 0.001;  = -0.167,  = 0.036). Coping-negative entered the regression equation ( = 19.154,  < 0.001). The female nursing students had higher scores in ownership dimension of AQ than their male counterparts (31.98 ± 3.26 vs. 29.21 ± 3.08,  = -4.442,  < 0.001).

Conclusions: The average AQ scores of Macao undergraduate nursing students were moderate. The female nursing students are more likely to attribute the cause of adversity to themselves, and specific psychosocial and cultural issues may be at play. There is a necessity for Macao nursing students to improve their ability to overcome setbacks. Special attention should be paid to the cultivation of students' positive coping styles.
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http://dx.doi.org/10.1016/j.ijnss.2021.02.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105537PMC
April 2021

Mechanical thrombectomy versus medical care alone in large ischemic core: An up-to-date meta-analysis.

Interv Neuroradiol 2021 May 14:15910199211016258. Epub 2021 May 14.

Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Objective: We compared outcomes and adverse events of thrombectomy versus medical management in acute ischemic stroke (AIS) patients with baseline large infarct core.

Methods: We searched Ovid MEDLINE(R) ALL, Cochrane Library Clinical Controlled Trials and EMBASE from inception to January 2021 for studies comparing thrombectomy and medical management alone in AIS patients who had ASPECTS <=7 or ischemic core volume >=50 ml. Imaging modalities to valuate ASPECTS and core volume were without restriction. The functional outcome was measured by mRS (modified Rankin Scale) score 0-2 at 90 days or discharge. The safety end point included the rates of mortality and sICH (symptomatic intracranial hemorrhage) or PH2 (parenchymal hematoma type 2).

Results: Fourteen studies with a total of 2547 patients (thrombectomy n = [1197]; medical care alone [n = 1350]) fulfilled our criteria. As for patients with low ASPECTS, pooled results indicated a higher odds of good functional outcome (OR = 3.47; 95% CI 1.99 to 6.07; P < 0.0001, I=66%) and a lower risk of mortality (OR = 0.62; 95% CI 0.46 to 0.83; P = 0.001, I=32%) in thrombectomy group compared with no thrombectomy group, but the risk of sICH or PH2 did not differ between two groups. As for patients with large core volume, both functional outcome and safety end point between two groups showed no statistically significant difference.

Conclusion: Thrombectomy remained safe and effective by careful selection in patients with low ASPECTS. More studies were warranted to explore contraindications for mechanical thrombectomy in AIS patients, especially in patients with large core volume.
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http://dx.doi.org/10.1177/15910199211016258DOI Listing
May 2021

Thymoquinone sensitizes human hepatocarcinoma cells to TRAIL-induced apoptosis via oxidative DNA damage.

DNA Repair (Amst) 2021 Jul 15;103:103117. Epub 2021 Apr 15.

Department of General Surgery, the First Hospital Affiliated of Shandong First Medical University (Qianfoshan Hospital), Jinan, Shandong, 250014, China. Electronic address:

Introduction: Hepatocellular carcinoma (HCC) remains one of the most predominant types of digestive system malignancies worldwide. TNF-related apoptosis-inducing ligand (TRAIL) is a biological cytokine with the mentioned specificity, but some tumor cells' resistance limits its use as a therapeutic approach. The present study aimed to investigate thymoquinone (TQ) and TRAIL's combined effect and the potential mechanisms in human hepatic HepG2 carcinoma cells.

Methods: Cell viability and IC dose for TQ and TRAIL, alone and in combination, were determined using the MTT method. ELISA evaluated the expression levels of 8-Hydroxy-2'-deoxyguanosine. The apoptosis rate was assessed by flow cytometry, ELISA cell death assay, and caspase 8 activity assays. The mRNA and protein evaluation of candidate genes, including survivin, Bcl-2, XIAP, c-IAP1, c-IAP2, and c-FLIP, were accomplished before and after the treatment using qRT-PCR and Western blot analysis, respectively.

Results: Our results showed that TQ synergistically increased TRAIL's cell toxic effects as follows: TQ plus TRAIL > TRAIL > TQ. TQ could sensitize the HepG2 cells against the TRAIL-induced apoptosis and amplify the caspase 8 activity. This outcome is achieved by decreasing the mRNA and protein expression levels of anti-apoptotic genes.

Conclusions: Our findings suggest that TQ can sensitize the human HCC cell line HepG2 against TRAIL by inducing the death receptor pathway. Moreover, these agents' combinational therapy might promise a therapeutic regimen for improving the clinical efficacy of TRAIL-induced apoptosis in patients with HCC.
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http://dx.doi.org/10.1016/j.dnarep.2021.103117DOI Listing
July 2021

No obvious association exists between mean platelet volume and hypertension subtypes.

Biomark Med 2021 Jun 14;15(8):577-584. Epub 2021 May 14.

Tianjin Key Laboratory of Lung Cancer Metastasis & Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, 300052, PR China.

To determine the association between mean platelet volume (MPV) and hypertension subtypes. 44,281 Chinese individuals were enrolled in this cross-sectional study. The mean blood pressure decreased with increasing MPV in females (p = 0.001) and increased MPV seemed to be a potential protective factor for isolated diastolic hypertension in models 1 and 2. The OR (CI) was 0.878 (0.789-0.976) for model 1 and 0.880 (0.789-0.981) for model 2 in males and 0.646 (0.495-0.841) for model 1 and 0.657 (0.503-0.858) for model 2 in females, when MPV was analyzed as a categorical variable. The OR (CI) was 0.947 (0.911-0.985) for Model 1 and 0.947 (0.910-0.985) for Model 2 in males, and 0.886 (0.807-0.973) for Model 1 and 0.892 (0.813-0.978) for Model 2 in females when MPV was analyzed as a continuous variable. However, the statistical difference of OR disappeared when we added blood-related covariates in Model 3. No obvious association exists between MPV and hypertension subtypes. Other blood parameters might have a greater impact on hypertension subtypes.
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http://dx.doi.org/10.2217/bmm-2020-0305DOI Listing
June 2021

SO Capture Using Porous Organic Cages.

Angew Chem Int Ed Engl 2021 May 12. Epub 2021 May 12.

Department of Chemistry, Materials Innovation Factory, Leverhulme Centre for Functional Materials Design, University of Liverpool, Liverpool, L69 7ZD, UK.

We report the first experimental investigation of porous organic cages (POCs) for the demanding challenge of SO capture. Three structurally related N-containing cage molecular materials were studied. An imine-functionalized POC (CC3) showed modest and reversible SO capture, while a secondary-amine POC (RCC3) exhibited high but irreversible SO capture. A tertiary amine POC (6FT-RCC3) demonstrated very high SO capture (13.78 mmol g ; 16.4 SO molecules per cage) combined with excellent reversibility for at least 50 adsorption-desorption cycles. The adsorption behavior was investigated by FTIR spectroscopy, C CP-MAS NMR experiments, and computational calculations.
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http://dx.doi.org/10.1002/anie.202104555DOI Listing
May 2021

Precise Identification of the Dimethyl Sulfoxide Triggered Tricarbonyldichlororuthenium(II) Dimer for Releasing CO.

J Phys Chem Lett 2021 May 12;12(19):4658-4665. Epub 2021 May 12.

Beijing National Laboratory for Condensed Matter Physics and CAS Key Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.

Low concentrations of carbon monoxide (CO) can play vital roles in pharmacological and physiological functions in the human body. The transition-metal carbonyl complexes of the tricarbonyldichlororuthenium(II) dimer [Ru(CO)Cl (CORM-2)] were proposed as CO-releasing molecules (CORMs) to improve the delivery efficiency of CO for therapeutic effects. The accurate identification of final products for CORMs in solution and the detailed mechanisms of the release of CO were the essential prerequisite for its effective physiological application, which have been deficient. In this study, utilizing the cutting-edge two-dimensional (2D) IR spectroscopy, with the intrinsic vibrational modes and the coupling information on dynamics of intramolecular vibrational energy redistribution (IVR), the final products of A, B, C, and E are accurately identified when CORM-2 is dissolved in dimethyl sulfoxide (DMSO). Furthermore, with the clues on intermolecular interaction and chemical exchange dynamics between different products, the transformations between different products are also directly characterized for the first time. These findings challenge the results from the classic 1D spectroscopic pattern, and they evidently demonstrated that the release of CO from CORM-2 in DMSO was slow and complicated with multiple reaction pathways. Combining with DFT simulations, the detailed mechanisms of release of CO for CORM-2 dissolved in DMSO are schematically proposed, which can significantly contribute to its drug optimization and pharmacological as well as physiological applications.
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http://dx.doi.org/10.1021/acs.jpclett.1c00905DOI Listing
May 2021