Publications by authors named "Long Wei"

222 Publications

Exosomal mRNA and lncRNA profiles in cord blood of preeclampsia patients.

J Matern Fetal Neonatal Med 2021 Sep 1:1-11. Epub 2021 Sep 1.

Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, PR China.

Background: Exosomes are endosome-derived membrane vesicles that contain numerous RNAs and allow intercellular communication. The roles of mRNAs and lncRNAs from umbilical cord blood exosomes in the development of preeclampsia (PE) remain unclear.

Methods: In the study, microarray technology was used to construct the differential mRNA and lncRNA expression profiles in umbilical cord blood exosomes between PE patients and normal controls.

Results: Totally, 120 differentially expressed mRNAs and 248 differentially expressed lncRNAs were identified. Pathway analysis showed that the differentially expressed mRNAs were related to glycolysis/gluconeogenesis, PI3K-Akt signaling pathway and JAK-STAT signaling pathway, which are critical in PE development. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted for the differential lncRNA-associated mRNAs. We found several significantly enriched pathways were closely associated with metabolic process, cell proliferation, differentiation, and apoptosis. Moreover, the constructed pathway network revealed key pathways in PE, including apoptosis and TGF-beta signaling pathway. Further analysis of lncRNA/miRNA interactions showed that most of the lncRNAs had miRNA binding sites, and some of them were associated with PE.

Conclusions: The study highlights the importance of exosomal mRNAs and lncRNAs in umbilical cord blood, and provides new insight into the development of PE.
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http://dx.doi.org/10.1080/14767058.2021.1966413DOI Listing
September 2021

ceRNA regulatory network of FIH inhibitor as a radioprotector for gastrointestinal toxicity by activating the HIF-1 pathway.

Mol Ther Nucleic Acids 2021 Sep 19;25:173-185. Epub 2021 May 19.

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China.

Given the relentless renewal ability of intestinal crypt-base stem cells, small intestine in the gastrointestinal (GI) tract is more vulnerable to radiation-induced disruption. Through promoting epithelial integrity and reducing intracellular reactive oxygen species (ROS) levels, hypoxia-inducible factors (HIFs) have been proved to exhibit radioprotective effects in the GI tract. Therefore, enhancing stability or transcriptional activity of HIFs might be a therapeutic strategy for developing radioprotectors. Factor inhibiting HIF (FIH or HIF-1AN) can hamper transcriptional capacity of HIF-1α via interacting with Asn803 in its C-terminal domain. Previously, we discovered promoting HIF-1α transcriptional activity by FIH inhibitor-N-oxalyl-D-phenylalanine (NOFD) exerts radioprotection on cells. However, the radioprotective effect of FIH inhibitor on the GI tract and its competing endogenous RNA (ceRNA) regulatory network from the FIH/HIF axis has never been addressed. Here we verified radioprotection of NOFD for the GI tract by an animal model and performed whole-transcriptome analysis to fully elucidate the radioprotective mechanism from the FIH/HIF axis against GI syndrome. We identified two novel circular RNAs (circRNAs) (circRNA_2909 and circRNA_0323) and two long non-coding RNAs (lncRNAs) (NONMMUT140549.1 and NONMMUT148249.1) that promote expression of and in the HIF-1 pathway by sponging microRNAs (miRNAs), especially mmu-miR-92a-1-5p. The de-repression of HIF-1α transcriptional capacity by inhibiting FIH proteomic activity suggests a new therapeutic strategy in alleviating radiation-induced GI syndrome.
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http://dx.doi.org/10.1016/j.omtn.2021.05.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8368776PMC
September 2021

Lattice Boltzmann modeling of interfacial mass transfer in a multiphase system.

Phys Rev E 2021 Jul;104(1-2):015307

Research Institute of Tsinghua University in Shenzhen, Shenzhen 518057, China and iCore Group Inc., Shenzhen 518057, China.

In the present study, a numerical model based on the lattice Boltzmann method (LBM) is proposed to simulate multiphase mass transfer, referred to as the CST-LB model. This model introduced continuum species transfer (CST) formulation by an additional collision term to model the mass transfer across the multiphase interface. The boundary condition treatment of this model is also discussed. In order to verify the applicability, the CST-LB model is combined with the pseudopotential multiphase model to simulate a series of benchmark cases, including concentration jump near the interface, gas dissolution in a closed system, species transport during drainage in a capillary tube, and multiphase species transport in the porous media. This CST-LB model can also be coupled with other multiphase LBMs since the model depends on the phase fraction field, which is not explicitly limited to specified multiphase models.
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http://dx.doi.org/10.1103/PhysRevE.104.015307DOI Listing
July 2021

Is Prenatal Diagnosis Necessary for Fetal Isolated Nasal Bone Absence or Hypoplasia?

Int J Gen Med 2021 11;14:4435-4441. Epub 2021 Aug 11.

Clinical Laboratory, Changzhou Children's Hospital Affiliated to Nantong Medical University, Changzhou, Jiangsu Province, People's Republic of China.

Purpose: This study aimed to explore the value of chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in the prenatal diagnosis of fetal isolated nasal bone absence (INBA) or isolated nasal bone hypoplasia (INBH). We hope to provide additional relevant information for clinical counseling.

Patients And Methods: From November 1, 2018, to March 1, 2020, 55 pregnant women with isolated nasal bone dysplasia were admitted to the Changzhou Maternity and Child Health Care Hospital. Based on the degree of abnormality, the patients were divided into two groups: INBA and INBH. CMA was performed on all patients. The clinical data and prenatal genetic diagnoses of the two groups were retrospectively analyzed. According to the requirements of WES for samples, 12 cases with negative CMA results were selected for the WES test.

Results: A total of 55 cases with INBA or INBH met the inclusion criteria. In 35INBA fetuses, there was one case of trisomy 21 and one case of 10q11.22 deletion (5.7Mb), and the abnormality rate was 5.71% (2/35). Compared with INBA fetuses, the abnormality rate was increased in the fetuses with INBH [15.00% (3/20)] (15.00% vs 5.71%); there was one case of 1q21.1 duplication (1.3Mb), one case of Xp22.31 duplication (1.67Mb), and one case of 4p deletion (7.6Mb). In a later retrospective study, two pathogenic variants were identified in two cases after the WES test; the abnormality rate was 16.67% (2/12), which involved and genes, respectively.

Conclusion: A preliminary study confirmed that molecular prenatal diagnosis should be performed in fetuses with INBA or INBH. CMA followed by WES is an effective method.
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http://dx.doi.org/10.2147/IJGM.S322359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8364966PMC
August 2021

Recent Progress on NIR-II Photothermal Therapy.

Front Chem 2021 29;9:728066. Epub 2021 Jul 29.

Tianjin Key Laboratory of Brain Science and Neuroengineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China.

Photothermal therapy is a very promising treatment method in the field of cancer therapy. The photothermal nanomaterials in near-infrared region (NIR-I, 750-900 nm) attracts extensive attention in recent years because of the good biological penetration of NIR light. However, the penetration depth is still not enough for solid tumors due to high tissue scattering. The light in the second near-infrared region (NIR-II, 1000-1700 nm) allows deeper tissue penetration, higher upper limit of radiation and greater tissue tolerance than that in the NIR-I, and it shows greater application potential in photothermal conversion. This review summarizes the photothermal properties of Au nanomaterials, two-dimensional materials, metal oxide sulfides and polymers in the NIR-II and their application prospects in photothermal therapy. It will arouse the interest of scientists in the field of cancer treatment as well as nanomedicine.
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http://dx.doi.org/10.3389/fchem.2021.728066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8358119PMC
July 2021

Automated robust SBPT planning using EUD-based prediction of SBRT plan for patients with lung cancer.

Comput Methods Programs Biomed 2021 Sep 5;209:106338. Epub 2021 Aug 5.

Raysearch China, Shanghai, PR China. Electronic address:

Purpose: To evaluate the quality of robust stereotactic body proton therapy (RSBPT) plans generated by one-clicking scripting method for patients with lung cancer.

Materials And Methods: Retrospective analysis was performed on fifty lung cancer patients whose plan with robustly stereotactic body radiation therapy (SBRT). Thirty out of fifty patients were used for training to build a regression model, based on robust SBRT reference doses, to predict EUD values of ROIs for robust SBPT planning. Thereafter, robust SBPT plans with both automated EUD-Based mimicking (Automated Robust Proton ARP) and manual (Manual Robust Proton MRP) methods were evaluated in the remaining 20 patients. Plans were compared in terms of dosimetric parameters and planning time.

Results: A statistically significantly improvement in target dose fall off was observed for ARP plans compare to MRP plans (Dose fall off: 135 for MRP and 88 for ARP, p < 0.01), while no differences in target coverage and conformity. A statistically significantly reduce in normal lung tissue were observed for ARP plans compare to MRP plans (Lung [D cGy (RBE)]: MRP: 478 vs. ARP: 351, p < 0.01; Lung [V (%)]: MRP: 16.1 vs. ARP: 12.1, p < 0.01; Lung [V (%)]: MRP: 8.5 vs. ARP: 6.8, p < 0.01). Planning time was reduced for ARP plans compare to MRP plans (optimization time: 12 min for MRP vs. 8 min for ARP; total plan time: 23 min for MRP vs. 18 min for ARP).

Conclusion: The automated robust SBPT plans using EUD-Based mimicking of SBRT reference dose improve target dose fall off, reduced the radiation doses to the lungs, reduce planning time, which might be beneficial for patient with lung cancer in clinical.
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http://dx.doi.org/10.1016/j.cmpb.2021.106338DOI Listing
September 2021

Variant of TSHR is Not a Frequent Cause of Congenital Hypothyroidism in Chinese Han Patients.

Int J Gen Med 2021 3;14:4135-4143. Epub 2021 Aug 3.

Department of Medical Genetics, Affiliated Changzhou Women and Children's Hospital, Nanjing Medical University, Changzhou, People's Republic of China.

Purpose: To screen variants of the thyroid stimulating hormone receptor () gene among congenital hypothyroidism (CH) patients.

Patients And Methods: We conducted a genetic screening of the gene in a cohort of 125 Chinese CH patients. Variants were detected by customized targeted next-generation sequencing.

Results: A total of 11 missense heterozygous variants were identified in 14 CH patients. Six variants were in the transmembrane domains, four variants were in the leucine-rich repeats and one variant was located in the hinge region of the TSHR protein. p.F525S was the most prevalent variant with an allele frequency of 0.016, followed by p.R450H with an allele frequency of 0.012. The allele frequency of most variants was higher in our cohort than those of other populations.

Conclusion: The prevalence of variants was 11.2%. Variant p.F525S was the most prevalent variant with an allele frequency of 0.016. The prevalence of variants was different from other populations.
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http://dx.doi.org/10.2147/IJGM.S322726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349214PMC
August 2021

State-of-art review on preparation, surface functionalization and biomedical applications of cellulose nanocrystals-based materials.

Int J Biol Macromol 2021 Sep 14;186:591-615. Epub 2021 Jul 14.

Department of Chemistry and the Tsinghua Center for Frontier Polyer Research, Tsinghua University, Beijing 100084, China. Electronic address:

Cellulose nanocrystals (CNCs) are a class of sustainable nanomaterials that are obtained from plants and microorganisms. These naturally derived nanomaterials are of abundant hydroxyl groups, well biocompatibility, low cost and biodegradable potential, making them suitable and promising candidates for various applications, especially in biomedical fields. In this review, the recent advances and development on the preparation, surface functionalization and biomedical applications of CNCs-based materials have been summarized and outlined. The main context of this paper could be divided into the following three parts. In the first part, the preparation strategies based on physical, chemical, enzymatic and combination techniques for preparation of CNCs have been summarized. The surface functionalization methods for synthesis CNCs-based materials with designed properties and functions were outlined in the following section. Finally, the current state about applications of CNCs-based materials for tissue engineering, medical hydrogels, biosensors, fluorescent imaging and intracellular delivery of biological agents have been highlighted. Moreover, current issues and future directions about the above aspects have also pointed out and discussed. We believe this review will attract great research attention of scientists from materials, chemistry, biomedicine and other disciplines. It will also provide some important insights on the future development of CNCs-based materials especially in biomedical fields.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.07.066DOI Listing
September 2021

The Association Between ABO Blood Group and Preeclampsia: A Systematic Review and Meta-Analysis.

Front Cardiovasc Med 2021 21;8:665069. Epub 2021 Jun 21.

Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

This meta-analysis comprehensively evaluated the association between ABO blood group and the risk of preeclampsia (PE). Systematic review and meta-analysis. PubMed, Web of Science, and ScienceDirect databases from their inception to September 23, 2020. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were obtained through random-effects and fixed-effects models according to heterogeneity. Meta-regression analysis was applied to explore the source of heterogeneity. We conducted a subgroup analysis by the publication year, study design, state, and Newcastle-Ottawa Scale (NOS) score. In addition, we calculated the rate of each ABO blood group in PE by total pooled effects. A total of 12 articles with 714,153 patients were included in our analysis. Compared with people without PE (control group), the O blood group presented a lower risk of PE (OR 0.95, 95% CI 0.93-0.97). The AB (OR 1.46, 95% CI 1.12-1.91) blood group presented a higher risk. However, the total pooled OR and 95% CI for the A (OR 1.02, 95% CI 0.90-1.16) and B (OR 1.02, 95% CI 0.98-1.05) blood groups were not significant. The funnel plot and linear regression equation showed that there was no publication bias for the O, A, or B blood groups (all > 0.05). However, the funnel plot and linear regression equation for the AB blood group were obviously asymmetric ( < 0.05), and the publication bias persisted even after the trim-and-fill method was applied ( < 0.05). Multivariable meta-regression analysis did not find a specific source of heterogeneity. The A blood group showed an association with early-onset PE (OR 0.53, 95% CI 0.33-0.83), and the other blood groups showed no significant differences. In PE, the rates of the O, A, B, and AB blood groups decreased gradually (0.39, 0.33, 0.19, 0.07). These findings suggest that pregnant women with AB blood group are more likely to develop PE, and more attention should be paid to AB blood group whose blood pressure is high but not sufficient to diagnose PE. Prospero CRD42021227930.
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http://dx.doi.org/10.3389/fcvm.2021.665069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256995PMC
June 2021

Retinex-Based Fast Algorithm for Low-Light Image Enhancement.

Entropy (Basel) 2021 Jun 13;23(6). Epub 2021 Jun 13.

School of Mechanical Engineering, Sichuan University, Chengdu 610065, China.

We proposed the Retinex-based fast algorithm (RBFA) to achieve low-light image enhancement in this paper, which can restore information that is covered by low illuminance. The proposed algorithm consists of the following parts. Firstly, we convert the low-light image from the RGB (red, green, blue) color space to the HSV (hue, saturation, value) color space and use the linear function to stretch the original gray level dynamic range of the V component. Then, we estimate the illumination image via adaptive gamma correction and use the Retinex model to achieve the brightness enhancement. After that, we further stretch the gray level dynamic range to avoid low image contrast. Finally, we design another mapping function to achieve color saturation correction and convert the enhanced image from the HSV color space to the RGB color space after which we can obtain the clear image. The experimental results show that the enhanced images with the proposed method have better qualitative and quantitative evaluations and lower computational complexity than other state-of-the-art methods.
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http://dx.doi.org/10.3390/e23060746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231777PMC
June 2021

Abnormal Fibrinogen Level as a Prognostic Indicator in Coronavirus Disease Patients: A Retrospective Cohort Study.

Front Med (Lausanne) 2021 14;8:687220. Epub 2021 Jun 14.

Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

The coronavirus disease (COVID-19) pandemic poses a global threat, and identification of its prognostic biomarkers could prove invaluable. Fibrinogen (FIB) could be one such indicator as coagulation and fibrinolysis abnormalities are common among COVID-19 patients. We examined the role of FIB levels in the prognosis of COVID-19. This retrospective cohort study enrolled 1,643 COVID-19 patients from the Leishenshan Hospital in Wuhan, China. The follow-up was conducted from February 8, 2020 to April 15, 2020. The cohort was divided into three groups according to the FIB level on admission, and associations with mortality and disease severity were determined using Cox and logistic regression analyses, respectively. Further, Kaplan-Meier (K-M) analyses by log-rank tests were used to assess the survival of patients with varying FIB levels. Patients with FIB < 2.2 g/L [hazard ratio (HR): 9.02, 95% confidence interval (CI): 1.91-42.59, = 0.006] and >4.2 g/L (HR: 4.79, 95% CI: 1.14-20.20, = 0.033) showed higher mortality risks compared to those with FIB between 2.2 and 4.2 g/L. The survival curves showed similar results in K-M analyses ( < 0.001). Additionally, an elevated FIB level was associated with a greater risk of developing critical disease (odds ratio: 2.16, 95% CI: 1.04-4.46, = 0.038) than a FIB level within the normal range. Abnormal FIB levels may be associated with mortality risk among COVID-19 patients and could predict critical disease development. Thus, assessment of FIB levels may assist in determining the prognosis of COVID-19 patients.
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http://dx.doi.org/10.3389/fmed.2021.687220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236504PMC
June 2021

Isomerization Dynamics in the Symmetric and Asymmetric Fragmentation of Ethane Dications.

J Phys Chem Lett 2021 Jun 17;12(24):5789-5795. Epub 2021 Jun 17.

Institute of Modern Physics, Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai 200433, China.

Hydrogen- or proton-migration-induced isomerization has recently been of concern for its critical role in the dissociation of organic molecules of astrophysical or biological relevance. Herein we present a combined experimental and theoretical study of the two-body C-C bond breakdown dissociation of ethane dication. For the asymmetric fragmentation channel CH + CH, the kinetic energy release measurements and quantum chemical calculations demonstrate that the reaction pathway involving hydrogen-migration-induced isomerization of [CH-CH] to [CH-CH] can be accessed the lowest triplet state rather than the ground singlet state of ethane dication. Interestingly, it is found that a considerable proportion of the yield of symmetric fragmentation CH + CH, which is usually considered from a direct Coulomb explosion and seemingly independent of isomerization, could come from the dissociation of ethane dication in the ground singlet state with the involvement of [CH-CH] isomerization to intermediate [HC(H)CH] of the diborane-like double-bridged structure.
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http://dx.doi.org/10.1021/acs.jpclett.1c01276DOI Listing
June 2021

circMTO1 sponges microRNA-219a-5p to enhance gallbladder cancer progression via the TGF-β/Smad and EGFR pathways.

Oncol Lett 2021 Jul 27;22(1):563. Epub 2021 May 27.

Department of Hepatobiliary Surgery, Lanzhou No. 2 People's Hospital, Lanzhou, Gansu 730046, P.R. China.

Circular mitochondrial translation optimization 1 homologue (circMTO1) has been reported to regulate the tumorigenesis of different types of cancer; however, the role of circMTO1 in gallbladder cancer (GBC) remains unknown. The present study aimed to identify the potential miRNAs and target genes of circMTO1 during GBC progression, and clarify the regulatory mechanism between circMTO1 and miRNAs or target genes. The present study performed MTT and Transwell assays, and Annexin V staining to assess cell viability, migration and apoptosis, respectively. In addition, a lymphatic vessel formation assay was performed to assess tube formation of human dermal lymphatic endothelial cells (HDLECs), and GBC-SD and NOZ cells. The results demonstrated that circMTO1 knockdown significantly attenuated the viability and migration of GBC cells and tube formation of HDLECs, and promoted apoptosis, indicating a tumor-promoting role of circMTO1. In addition, transfection with microRNA (miRNA/miR)-219a-5p inhibitor rescued short hairpin RNA-circMTO1-inhibited tumorigenesis of GBC cells, suggesting that miR-219a-5p acts as a downstream effector for circMTO1. Mechanistically, transfection with miR-219a-5p mimic suppressed the expression levels of Smad2/4 and epidermal growth factor receptor. Analysis of The Cancer Genome Atlas datasets revealed that circMTO1 expression was associated with overall survival and the stage of patients with GBC. Taken together, the results of the present study provide novel insight for the role of circMTO1-induced GBC tumorigenesis via regulation of miR-219a-5p expression.
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http://dx.doi.org/10.3892/ol.2021.12824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185704PMC
July 2021

Simultaneous surface functionalization and drug loading: A novel method for fabrication of cellulose nanocrystals-based pH responsive drug delivery system.

Int J Biol Macromol 2021 Jul 2;182:2066-2075. Epub 2021 Jun 2.

Department of Chemistry and the Tsinghua Center for Frontier Polymer Research, Tsinghua University, Beijing 100084, China.

Herein, a novel strategy for surface functionalization and drug loading of cellulose nanocrystals (CNCs) through formation of hydrazone bonds between functionalized CNCs and aldehyde group containing polyethylene glycol (CHO-PEG)/anticancer drug doxorubicin (DOX) was reported for the first time. DOX could be loaded on PEGylated CNCs with high capacity and released from drug complexes (P-CNCs-D) with pH dependent behavior. The biological evaluation results demonstrated that drug carriers (CNCs-EBO-NH) showed negative cytotoxicity while DOX could be transported into cells and exhibits desirable anticancer effects. As compared with other method, the method developed in this work is rather simple and effective and can be achieved for simultaneous for surface functionalization and drug loading in a one-pot route. This work will open a new avenue for fabrication of various multifunctional composites based on other carbohydrate polymers or materials and to explore their applications in biomedical fields.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.193DOI Listing
July 2021

Effect of Third-Stage Heat Treatments on Microstructure and Properties of Dual-Phase Titanium Alloy.

Materials (Basel) 2021 May 24;14(11). Epub 2021 May 24.

College of Materials and Metallurgy, Guizhou University, Guiyang 550025, China.

Two-phase TC21 titanium alloy samples were solution-treated at 990 °C (β phase zone) and cooled by furnace cooling (FC), air cooling (AC), and water quenching (WQ), respectively. The second solution stage treatment was carried out at 900 °C (α + β phase zone), then aging treatment was performed at 590 °C. The influence of the size and quantity of the α phase on the properties of the sample were studied. The experimental results showed as the cooling rate increased after the first solution stage treatment, wherein the thickness of primary layer α gradually decreased, and the tensile strength and yield strength gradually increased. After the second solution stage treatment, the tensile properties of samples increased due to the quantity of layers α increased. The aging treatment promoted the precipitation of the dispersed α phase and further improved the tensile strength. After the third solution stage treatments, the FC samples with more β-phase had the best comprehensive mechanical properties.
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http://dx.doi.org/10.3390/ma14112776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197205PMC
May 2021

A novel peptide ameliorates TNFα- and LPS-induced endothelia dysfunction in preeclampsia.

Am J Hypertens 2021 May 26. Epub 2021 May 26.

Women's Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, 210004, China.

Objective: To investigate the protective effects of the novel peptide AEDPPE on tumor necrosis factor α (TNFα)- and lipopolysaccharide (LPS)-induced injury in the vascular endothelium in preeclampsia.

Methods: The effects of AEDPPE on TNFα-induced vascular endothelial injury were assessed by enzyme-linked immunosorbent assay (ELISA), quantitative real-time quantitative PCR (qRT-PCR), mitochondrial membrane potential assay, cell counting kit-8(CCK-8) assay, THP-1 monocyte-human umbilical vein endothelial cell(HUVEC) adhesion assay, endothelial tube-forming assay, transcriptomic analysis, preeclamptic symptom analysis and histological analysis in preeclampsia-like rat models induced by LPS.

Results: AEDPPE alleviated the upregulation of antiangiogenic factors including sFlt-1, ET-1 and tPA and attenuated the reduction in mitochondrial potential induced by TNFα in HUVECs.In addition, AEDPPE treatment counteracted the decrease in tube formation and decreased the numbers of THP-1 monocytes attached to HUVECs caused by TNFα. Mechanistically, cytokine -cytokine receptor interactions enriched many genes and the TNF signaling pathway may be involved in this phenomenon. Moreover, cotreatment with LPS and AEDPPE significantly reversed the preeclampsia-like phenotype including hypertension and proteinuria and improved the functions of the kidney and placenta.

Conclusions: AEDPPE effectively ameliorated the vascular endothelial injury induced by TNFα and LPS in preeclampsia. We suggest that AEDPPE may be a novel therapeutic candidate for preeclampsia treatment. These findings demonstrate that AEDPPE may play an effective role in ameliorating vascular endothelial dysfunction and be a potential therapeutic agent for preeclampsia.
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http://dx.doi.org/10.1093/ajh/hpab086DOI Listing
May 2021

A mitochondria-targeted thiazoleorange-based photothermal agent for enhanced photothermal therapy for tumors.

Bioorg Chem 2021 08 30;113:104954. Epub 2021 Apr 30.

Allan H. Conney Laboratory for Anticancer Research, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen 529020, China. Electronic address:

Organic small molecules with near-infrared (NIR) absorption hold great promise as the phototheranostic agents for clinical translation by virtue of their inherent merits such as well-defined chemical structure, high purity and good reproducibility. Probes that happen to be based on cyanine dyes exhibit strong NIR-absorbing and efficient photothermal conversion, representing a new class of photothermal agents (PAs) for photothermal therapy (PTT), and taking into account the heat susceptibility of Mitochondria (Mito), we designed and prepared a mitochondria-targeted organic small molecule (Mito-BWQ) based on thiazole orange maternal unit that can effectively kill tumor cells through the hyperpyrexia generated in the lesions under exogenous laser irradiation. The Confocal laser scanning microscope was employed to determine the preferential targeting of Mito-BWQ to the mitochondria of MCF-7 cells and U87 cells. When subjected to 600 nm laser radiation, Mito-BWQ produced an increase in temperature in test systems and this increase was dependent on both the laser power and probe concentration. In vitro tests, cytotoxicity was observed when cells were incubated with Mito-BWQ and exposed to laser irradiation. The PTT in vivo also showed that Mito-BWQ performed remarkably in tumor inhibition. This study thus provides a vital starting point for the creation of thiazole orange-based PTT formulations and promotes further advances in the field of PAs-based anticancer research and therapy.
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http://dx.doi.org/10.1016/j.bioorg.2021.104954DOI Listing
August 2021

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.

Age Ageing 2021 Sep;50(5):1546-1556

Critical Care and Peri-operative Medicine, Monash Health, Melbourne, Australia.

Background: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients.

Objective And Design: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome.

Subjects And Methods: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay.

Results: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05).

Conclusions: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.
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http://dx.doi.org/10.1093/ageing/afab078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437072PMC
September 2021

Behavior of bladder-type inflatable anchors in sand: Physical modeling.

Sci Prog 2021 Apr-Jun;104(2):368504211015106

Key Laboratory of Metallogenic Prediction of Nonferrous Metals and Geological Environment Monitoring (Central South University), Ministry of Education, Changsha, Hunan, China.

This paper describes an investigation into the performance and pull-out capacity of a bladder-type inflatable anchor. The inflatable anchor is a type of support member used in foundation pit support engineering. Based on improvements and innovations, the multi-bladder-type inflatable anchor consists of two or more hydraulically inflated rubber membranes that are embedded in unconsolidated earth and then inflated to provide pull-out capacity. The primary objective of this study was to investigate the impact of inflation pressure, embedment depth, number of bladders, bladder length, and rubber film thickness on the pull-out capacity and displacement of the inflatable anchor. The tests were carried out in a cylindrical steel test chamber filled with medium coarse sand. The pull-out behavior of the bladder-type inflatable anchor and the five variables was investigated, and the benchmark values for all tests are determined by similarity ratio. Compared with the single bladder inflatable anchor, under the same conditions, the ultimate pull-out capacity of the two bladder-type inflatable anchor is 1.2 times higher, with ultimate displacement only 37.5% of the former, the ultimate pull-out capacity of the three bladder-type inflatable anchor is 1.7 times higher, with ultimate displacement only 32.3% of the former. The two bladder-type inflatable anchor is superior to the single bladder inflatable anchor and the multi-bladder-type has higher ultimate pull-out capacity and greater stiffness. The inflation pressure and the rubber film thickness have a significant influence on the bearing capacity. The number of bladders effectively controls the ultimate displacement.
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http://dx.doi.org/10.1177/00368504211015106DOI Listing
May 2021

Ultrasensitive Nanopore Sensing of Mucin 1 and Circulating Tumor Cells in Whole Blood of Breast Cancer Patients by Analyte-Triggered Triplex-DNA Release.

ACS Appl Mater Interfaces 2021 May 27;13(18):21030-21039. Epub 2021 Apr 27.

Department of Laboratory Medicine, State Key Laboratory of Biotherapy and Cancer Center, Med+X Center for Manufacturing, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China.

The characterization of circulating tumor cells (CTCs) by liquid biopsy has a great potential for precision medicine in oncology. Here, a universal and tandem logic-based strategy is developed by combining multiple nanomaterials and nanopore sensing for the determination of mucin 1 protein (MUC1) and breast cancer CTCs in real samples. The strategy consists of analyte-triggered signal conversion, cascaded amplification via nanomaterials including copper sulfide nanoparticles (CuS NPs), silver nanoparticles (Ag NPs), and biomaterials including DNA hydrogel and DNAzyme, and single-molecule-level detection by nanopore sensing. The amplification of the non-DNA nanomaterial gives this method considerable stability, significantly lowers the limit of detection (LOD), and enhances the anti-interference performance for complicated samples. As a result, the ultrasensitive detection of MUC1 could be achieved in the range of 0.0005-0.5 pg/mL, with an LOD of 0.1 fg/mL. Moreover, we further tested MUC1 as a biomarker for the clinical diagnosis of breast cancer CTCs under double-blind conditions on the basis of this strategy, and MCF-7 cells could be accurately detected in the range from 5 to 2000 cells/mL, with an LOD of 2 cells/mL within 6 h. The detection results of the 19 clinical samples were highly consistent with those of the clinical pathological sections, nuclear magnetic resonance imaging, and color ultrasound. These results demonstrate the validity and reliability of our method and further proved the feasibility of MUC1 as a clinical diagnostic biomarker for CTCs.
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http://dx.doi.org/10.1021/acsami.1c03538DOI Listing
May 2021

Differential circular RNA expression profiles in umbilical cord blood exosomes from preeclampsia patients.

BMC Pregnancy Childbirth 2021 Apr 15;21(1):303. Epub 2021 Apr 15.

Department of Neonatology, The Affiliated Wuxi Children's Hospital of Nanjing Medical University, Wuxi, 214023, China.

Background: Exosomal circular RNAs (circRNAs) are emerging as important regulators of physiological development and disease pathogenesis. However, the roles of exosomal circRNAs from umbilical cord blood in preeclampsia (PE) occurrence remains poorly understood.

Methods: We used microarray technology to establish the differential circRNA expression profiles in umbilical cord blood exosomes from PE patients compared with normal controls. Bioinformatics analysis was conducted to further predict the potential effects of the differentially expressed circRNAs and their interactions with miRNAs.

Results: According to the microarray data, we identified 143 significantly up-regulated circRNAs and 161 significantly down-regulated circRNAs in umbilical cord blood exosomes of PE patients compared with controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses showed that circRNA parental genes involved in the regulation of metabolic process, trophoblast growth and invasion were significantly enriched, which play important roles in PE development. Moreover, pathway network was constructed to reveal the key pathways in PE, such as PI3K-Akt signaling pathway. Further circRNA/miRNA interactions analysis demonstrated that most exosomal circRNAs had miRNA binding sites, and some miRNAs were associated with PE.

Conclusions: Our results highlight the importance of exosomal circRNAs in the pathogenesis of PE and lay a foundation for extensive studies on the role of exosomal circRNAs in PE development.
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http://dx.doi.org/10.1186/s12884-021-03777-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051099PMC
April 2021

Comparing the Value of Cystatin C and Serum Creatinine for Evaluating the Renal Function and Predicting the Prognosis of COVID-19 Patients.

Front Pharmacol 2021 22;12:587816. Epub 2021 Mar 22.

Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Coronavirus disease- (COVID-19-) related renal function abnormality is associated with poor prognosis. However, the clinical significance of dynamic changes in renal function indicators has not been studied, and no studies have evaluated the renal function in COVID-19 patients by cystatin C. This study aimed to evaluate the effect of abnormal renal function on admission on prognosis of COVID-19 patients and the prognostic value of various renal function indicators. A total of 1,764 COVID-19 patients without a history of chronic kidney disease were categorized into two groups, an elevated cystatin C group and a normal cystatin C group, based on the results of renal function tests on admission. The clinical characteristics were compared between the two groups, and logistic or Cox regression analyses were performed to explore the associations between elevated cystatin C/serum creatinine levels and disease severity and survival. We also performed receiver operating characteristic (ROC) curve, Kaplan-Meier survival, and curve fitting analyses. When adjusted for several significant clinical variables, elevated cystatin C levels on admission were independent predictors of disease severity ( < 0.001), and elevated creatinine levels were independent predictors of death ( = 0.020). Additionally, the ROC curve analysis shows that elevated cystatin C levels [area under the curve (AUC): 0.656] have a better predictive value for disease severity than elevated creatinine levels (AUC: 0.540). The survival curves of patients with elevated cystatin C/creatinine levels show a sharper decline than those of patients with normal cystatin C/creatinine levels ( < 0.001). The curve fitting analysis revealed that, compared to the flat curves of cystatin C and creatinine levels for patients who survived, the curves for patients who died kept rising, and cystatin C levels rose above the normal range earlier than creatinine. Elevated cystatin C, which occurs earlier than serum creatinine, is useful for the early detection of renal function abnormality and might have better predictive value for disease severity in COVID-19 patients, while elevated serum creatinine may have a better predictive value for risks of death.
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http://dx.doi.org/10.3389/fphar.2021.587816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019901PMC
March 2021

Clinical importance of the distribution of pulmonary artery embolism in acute pulmonary embolism.

J Int Med Res 2021 Apr;49(4):3000605211004769

Department of Geriatrics, Linyi People's Hospital, Linyi, China.

Objective: To explore the clinical importance of the distribution of pulmonary artery embolism in acute pulmonary embolism (APE).

Methods: Sixty-four patients with APE were classified into mixed-type and distal-type pulmonary embolism groups. Their right ventricular systolic pressure (RVSP) and disease duration were recorded, and the diameter of their right ventricles was measured by ultrasound. The computed tomography angiographic clot load was determined as a Mastora score.

Results: Patients with distal-type pulmonary embolisms had significantly lower RVSPs (44.92 ± 17.04 vs 55.69 ± 17.66 mmHg), and significantly smaller right ventricular diameters (21.08 ± 3.06 vs 23.37 ± 3.48 mm) than those with mixed-type pulmonary embolisms. Additionally, disease duration was significantly longer in patients with distal-type pulmonary embolisms (14.33 ± 11.57 vs 8.10 ± 7.10 days), and they had significantly lower Mastora scores (20.91% ± 18.92% vs 43.96% ± 18.30%) than patients with mixed-type pulmonary embolisms. After treatment, RVSPs decreased significantly in patients with both distal-type and mixed-type pulmonary embolisms. Right ventricle diameters also decreased significantly in patients with mixed-type pulmonary embolisms after treatment.

Conclusion: Patients with mixed-type pulmonary embolisms are significantly more susceptible to pulmonary hypertension, enlarged right ventricular diameters, and shorter durations of disease than those with distal-type pulmonary embolisms. The distribution of pulmonary artery embolism in APE can provide a clinical reference.
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http://dx.doi.org/10.1177/03000605211004769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033481PMC
April 2021

Three functionally redundant plant-specific paralogs are core subunits of the SAGA histone acetyltransferase complex in Arabidopsis.

Mol Plant 2021 Jul 15;14(7):1071-1087. Epub 2021 Mar 15.

College of Life Sciences, Beijing Normal University, Beijing, China; National Institute of Biological Sciences, Beijing 102206, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 10084, China. Electronic address:

The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is an evolutionarily conserved histone acetyltransferase complex that has a critical role in histone acetylation, gene expression, and various developmental processes in eukaryotes. However, little is known about the composition and function of the SAGA complex in plants. In this study, we found that the SAGA complex in Arabidopsis thaliana contains not only conserved subunits but also four plant-specific subunits: three functionally redundant paralogs, SCS1, SCS2A, and SCS2B (SCS1/2A/2B), and a TAF-like subunit, TAFL. Mutations in SCS1/2A/2B lead to defective phenotypes similar to those caused by mutations in the genes encoding conserved SAGA subunits HAG1 and ADA2B, including delayed juvenile-to-adult phase transition, late flowering, and increased trichome density. Furthermore, we demonstrated that SCS1/2A/2B are required for the function of the SAGA complex in histone acetylation, thereby promoting the transcription of development-related genes. These results together suggest that SCS1/2A/2B are core subunits of the SAGA complex in Arabidopsis. Compared with SAGA complexes in other eukaryotes, the SAGA complexes in plants have evolved unique features that are necessary for normal growth and development.
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http://dx.doi.org/10.1016/j.molp.2021.03.014DOI Listing
July 2021

Rhizobium symbiosis modulates the accumulation of arsenic in Medicago truncatula via nitrogen and NRT3.1-like genes regulated by ABA and linalool.

J Hazard Mater 2021 08 8;415:125611. Epub 2021 Mar 8.

College of Grassland Agriculture, Northwest A&F University, Yangling, Shaanxi 712100, People's Republic of China. Electronic address:

Arsenic (As) contamination is a worldwide problem and threatens human health. Here, we found that Rhizobium symbiosis can improve the tolerance to arsenate [As(V)], and a wild type R. meliloti Rm5038 symbiosis can significantly decrease the accumulation of As in Medicago truncatula shoots. The As content in plants could be decreased by nitrogen and the mutation of nitrate transporter NRT3.1. The expression of M. truncatula NRT3.1-like gene NRT3.1L1 could reverse the As(V)-tolerance phenotype of the Arabidopsis nrt3.1 mutant. Rm5038 symbiosis significantly increased the level of nitrogen in the shoot and reduced the expression of NRT3.1Ls in plants afflicted by As(V). The genetic analyses of aba2-1, pyr1/pyl1/2/4/5/8, and abi1-2/abi2-2/hab1-1/pp2ca-1 mutants revealed that abscisic acid (ABA) signaling regulates the tolerance of plants to As(V). ABA and linalool could promote the expression of NRT3.1Ls, however, their root biosynthesis was inhibited by ammonium, the first form of nitrogen fixed by Rhizobium symbiosis. Moreover, ABA and linalool may also control As and nitrate accumulation in Rhizobium symbionts via signaling pathways other than ammonia and NRT3.1Ls. Thus, Rhizobium symbiosis modulates the accumulation of As in plants via nitrogen and NRT3.1Ls regulated by ABA and linalool, which provides novel approaches to reduce As accumulation in legume crops.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125611DOI Listing
August 2021

Therapeutic role of d-pinitol on experimental colitis via activating Nrf2/ARE and PPAR-γ/NF-κB signaling pathways.

Food Funct 2021 Mar 24;12(6):2554-2568. Epub 2021 Feb 24.

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.

Ulcerative colitis is a recrudescent intestinal inflammation coupled with diarrhea, weight loss, pus, and blood stool, which seriously impacts the quality of patient life. d-Pinitol, which can be a food supplement isolated from the food plant-like soybeans, Ceratonia siliqua Linn and Bruguiera gymnorrhiza, has been proved to show anti-oxidative and anti-inflammatory effects. However, the potential mechanism of d-pinitol still remains ill-defined contemporarily. In the current study, the therapeutic effect and potential mechanisms of d-pinitol against colitis were investigated. Oxidative stress and inflammation of experimental colitis were caused by 3% DSS treatment once daily for 7 days. During DSS treatment, the mice of the positive drug group and three other groups were orally administered SASP or d-pinitol once daily. Clinical symptoms were analyzed, and macroscopic scores were calculated. The levels of oxidative and inflammatory cytokines were measured using assay kits and RT-PCR. Additionally, the protein expression of the Nrf2/ARE pathway and PPAR-γ was measured by Western blot. Results showed that d-pinitol enormously alleviated DSS-induced bodyweight loss, colon shortening, and histological injuries, achieving a therapeutic efficacy superior to SASP. Moreover, the oxidative stress and colonic inflammatory response were mitigated. d-pinitol not only significantly activated the Nrf2/ARE signaling pathway via facilitating the translocation of Nrf2 from sitoplazma to cytoblast, upregulating the protein expression levels of GCLC, GCLM, HO-1, and NQO1, but also improved the PPAR-γ level by binding to the active site of PPAR-γ, when suppressing NF-κB p65 and IκBα phosphorylation. In conclusion, d-pinitol exhibited a dramatic anti-colitis efficacy by activating the Nrf2/ARE pathway and PPAR-γ. Hence, d-pinitol may be a promising therapeutic drug against UC in the future.
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http://dx.doi.org/10.1039/d0fo03139aDOI Listing
March 2021

Co-delivery of PSMA antigen epitope and mGM-CSF with a cholera toxin-like chimeric protein suppressed prostate tumor growth via activating dendritic cells and promoting CTL responses.

Vaccine 2021 03 19;39(11):1609-1620. Epub 2021 Feb 19.

School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, PR China. Electronic address:

Subunit vaccines derived from tumor antigens play a role in tumor therapy because of their unique advantages. However, because of the weak immunogenicity of peptides in subunit vaccines, it is difficult to trigger an effective cytotoxic T lymphocyte (CTL) response, which is critical for cancer therapy. A requirement for the activation of CTL cells by exogenous antigens is the stimulation of antigen presenting cells (APC) with the help of adjuvants and cross-presentation to T lymphocytes. Standard nonconjugated adjuvant-peptide mixtures do not ensure co-targeting of the antigen and the adjuvant to the same APC, which limits the effects of adjuvants. In this study, a fusion protein consisting of murine granulocyte-macrophage colony stimulating factor (mGM-CSF) fused with CTA2 (A2 subunit of cholera toxin) was generated and assembled with CTB-PSMA624-632 (prostate specific membrane antigen (PSMA) peptide 624-632 fused to CTB) to obtain a cholera toxin-like protein. The chimeric protein retained the biological activity of mGM-CSF and had stronger GM1 binding activity than (CTB-PSMA624-632)5. C57BL/6J mice immunized with the CT-like chimeric protein exhibited delayed tumor growth following challenge with human PSMA-EGFP-expressing RM-1 cells. Experiment results showed that the CT-like chimeric protein could induce the maturation of DC cells and improve CTL responses. Overall, these results indicate that the nasal administration of a CT-like chimeric protein vaccine results in the development of effective immunity against prostate tumor cells and might be useful for future clinical anti-tumoral applications.
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http://dx.doi.org/10.1016/j.vaccine.2021.02.002DOI Listing
March 2021

Decreased CO Levels as Indicators of Possible Mechanical Ventilation-Induced Hyperventilation in COVID-19 Patients: A Retrospective Analysis.

Front Public Health 2020;8:596168. Epub 2021 Jan 8.

Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China.

Six months since the outbreak of coronavirus disease (COVID-19), the pandemic continues to grow worldwide, although the outbreak in Wuhan, the worst-hit area, has been controlled. Thus, based on the clinical experience in Wuhan, we hypothesized that there is a relationship between the patient's CO levels and prognosis. COVID-19 patients' information was retrospectively collected from medical records at the Leishenshan Hospital, Wuhan. Logistic and Cox regression analyses were conducted to determine the correlation between decreased CO levels and disease severity or mortality risk. The Kaplan-Meier curve analysis was coupled with the log-rank test to understand COVID-19 progression in patients with decreased CO levels. Curve fitting was used to confirm the correlation between computed tomography scores and CO levels. Cox regression analysis showed that the mortality risk of COVID-19 patients correlated with decreased CO levels. The adjusted hazard ratios for decreased CO levels in COVID-19 patients were 8.710 [95% confidence interval (CI): 2.773-27.365, < 0.001], and 4.754 (95% CI: 1.380-16.370, = 0.013). The adjusted odds ratio was 0.950 (95% CI: 0.431-2.094, = 0.900). The Kaplan-Meier survival curves demonstrated that patients with decreased CO levels had a higher risk of mortality. Decreased CO levels increased the mortality risk of COVID-19 patients, which might be caused by hyperventilation during mechanical ventilation. This finding provides important insights for clinical treatment recommendations.
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http://dx.doi.org/10.3389/fpubh.2020.596168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7874065PMC
February 2021

Molecular Recognition and Imaging of Human Telomeric G-Quadruplex DNA in Live Cells: A Systematic Advancement of Thiazole Orange Scaffold To Enhance Binding Specificity and Inhibition of Gene Expression.

J Med Chem 2021 02 9;64(4):2125-2138. Epub 2021 Feb 9.

School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, P. R. China.

A series of fluorescent ligands, which were systematically constructed from thiazole orange scaffold, was investigated for their interactions with G-quadruplex structures and antitumor activity. Among the ligands, compound was identified to exhibit excellent specificity toward telomere G4-DNA over other nucleic acids. The affinity of -Htg24 was almost 5 times higher than that of double-stranded DNA and promoter G4-DNA. Interaction studies showed that may bind to both G-tetrad and the lateral loop near the 5'-end. The intracellular colocalization with BG4 and competition studies with BRACO19 reveal that may interact with G4-structures. Moreover, reduces the telomere length and downregulates hTERC and hTERT mRNA expression in HeLa cells. The cytotoxicity of against cancer cells (IC = 12.7-16.2 μM) was found to be generally higher than noncancer cells (IC = 52.3 μM). The findings may support that the ligand is telomere G4-DNA specific and may provide meaningful insights for anticancer drug design.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01656DOI Listing
February 2021

High-performance coded aperture gamma camera based on monolithic GAGG:Ce crystal.

Rev Sci Instrum 2021 Jan;92(1):013106

Beijing Engineering Research Center of Radiographic Techniques and Equipment, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049, China.

A 50 × 50 × 10 mm monolithic gadolinium aluminum gallium garnet (GdAlGaO; GAGG):Ce crystal coupled to a 8 × 8 silicon photomultiplier (SiPM) array was developed; it showed very good system uniformity and a high energy resolution of 7.4% at 662 keV. By using a convolutional neural network-based positioning algorithm and a fan-beam calibration method, the detector achieved a position resolution of ∼1.4 mm and a depth of interaction resolution of ∼2 mm. Based on this high-performance monolithic detector, we developed a coded aperture gamma camera. A 1-mCi Cs-137 source centered at a 2-m distance from the mask could be reconstructed with a signal-to-noise ratio of 6.5 in 1 s. Furthermore, the imaging ability of a low-energy Am-241 source and a low-activity Cs-137 source when the background-to-signal ratio was approximately 1:1 and a double low-activity source (Cs-137 and Na-22) was demonstrated. It is shown that the monolithic-crystal-based coded aperture gamma camera can achieve high performance and has a large potential for further improvement.
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http://dx.doi.org/10.1063/5.0035991DOI Listing
January 2021
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