Publications by authors named "Tao Cai"

242 Publications

Does letrozole treatment have favorable effects on the lipid profile? A systematic review and meta-analysis of randomized clinical trials.

Steroids 2021 Jun 8;172:108875. Epub 2021 Jun 8.

Department of Medical Service, No. 901 Hospital of Joint Logistics Support Force, Hefei City, Anhui Province 230001, China. Electronic address:

As an aromatase inhibitor, letrozole reduces estrogen levels, affecting lipid indices because of the positive role of estrogens in modulating lipoproteins and lipids. Thus, our aim was to meta-analyze data regarding letrozole administration and its effects on the traditional lipid profile. A systematic review and meta-analysis of randomized clinical trials (RCTs) were performed based on the PRISMA guidelines. Web of Science, Scopus, PubMed/Medline, and EMBASE databases were searched until February 11, 2021. From 341 potentially relevant publications, 8 RCTs were selected. All studies used 2.5 mg/d of letrozole. Total cholesterol changed significantly by -6.28 mg/dL (95% CI: -8.73, -3.84, P < 0.001) and HDL-C by -4.40 mg/dL (95% CI: -5.30 to -3.50, p < 0.001) in letrozole group when compared to the control group. Taking into account this comparison between groups, in contrast, LDL-C (WMD: -2.50 mg/dL, 95% CI: -9.94, 4.93, p = 0.510) and triglycerides (WMD: -0.89 mg/dL, 95% CI: -6.87 to 5.07, p = 0.768) did not alter. In conclusion, letrozole administration decreased the concentrations of HDL-C and tocal cholesterol, but not of triglycerides and LDL-C.
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http://dx.doi.org/10.1016/j.steroids.2021.108875DOI Listing
June 2021

Corrigendum to "Mitigating NO emissions from an ammonia-fueled micro-power system with a perforated plate implemented" [J. Hazard. Mater. 401 (2021) 123848].

Authors:
Tao Cai Dan Zhao

J Hazard Mater 2021 Jun 4;418:126179. Epub 2021 Jun 4.

Department of Mechanical Engineering, College of Engineering, University of Canterbury, Private Bag 4800, Christchurch 8140, New Zealand. Electronic address:

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http://dx.doi.org/10.1016/j.jhazmat.2021.126179DOI Listing
June 2021

Soybean residue based biochar prepared by ball milling assisted alkali activation to activate peroxydisulfate for the degradation of tetracycline.

J Colloid Interface Sci 2021 Oct 19;599:631-641. Epub 2021 Apr 19.

College of Environmental Science and Engineering, Hunan University, Lushan South Road, Yuelu District, Changsha 410082, PR China; Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Lushan South Road, Yuelu District, Changsha 410082, PR China. Electronic address:

The advanced oxidation process (AOPs) has caused great concern in recent years. Among them, biochar has been widely studied as a catalyst for advanced oxidation process because of its low price and low environmental risk. In this study, a novel ball milling assisted KOH activation biochar (MKBC) was prepared and applied in peroxydisulfate (PDS) activation to degrade tetracycline hydrochloride (TC-H). In comparison with the oxidation (3.48%) by PDS alone and adsorption (36.19%) by MKBC alone, the removal rate of TC-H was increased to 84.15% in the MKBC/PDS system, indicating that MKBC can successfully activate PDS. Besides, the catalytic activity of the MKBC to activate PDS for the degradation of TC-H is 58.33% higher than that of pristine biochar (PBC). In addition, MKBC has outstanding stability that after three repeated experiments, the removal rate of TC-H by the MKBC/PDS system still remains 77.35%. Meanwhile, the mechanism was investigated that the singlet oxygen (O) seized the principal position in the degradation of TC-H in the PDS/MKBC system. This study explored a novel, solvent-free and economic method to propose this extraordinary biochar, which provided a new strategy for the future research of biochar.
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http://dx.doi.org/10.1016/j.jcis.2021.04.074DOI Listing
October 2021

Atlas of breast cancer infiltrated B-lymphocytes revealed by paired single-cell RNA-sequencing and antigen receptor profiling.

Nat Commun 2021 04 12;12(1):2186. Epub 2021 Apr 12.

National Institute of Biological Sciences, Beijing, China.

To gain mechanistic insights into the functions and developmental dynamics of tumor-infiltrated immune cells, especially B-lymphocytes, here we combine single-cell RNA-sequencing and antigen receptor lineage analysis to characterize a large number of triple-negative breast cancer infiltrated immune cells and report a comprehensive atlas of tumor-infiltrated B-lymphocytes. The single-cell transcriptional profiles reveal significant heterogeneity in tumor-infiltrated B-cell subgroups. The single-cell antigen receptor analyses demonstrate that compared with those in peripheral blood, tumor-infiltrated B-cells have more mature and memory B-cell characteristics, higher clonality, more class switching recombination and somatic hypermutations. Combined analyses suggest local differentiation of infiltrated memory B-cells within breast tumors. The B-cell signatures based on the single-cell RNA-sequencing results are significantly associated with improved survival in breast tumor patients. Functional analyses of tumor-infiltrated B-cell populations suggest that mechanistically, B-cell subgroups may contribute to immunosurveillance through various pathways. Further dissection of tumor-infiltrated B-cell populations will provide valuable clues for tumor immunotherapy.
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http://dx.doi.org/10.1038/s41467-021-22300-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042001PMC
April 2021

Unique MIL-53(Fe)/PDI Supermolecule Composites: Z-Scheme Heterojunction and Covalent Bonds for Uprating Photocatalytic Performance.

ACS Appl Mater Interfaces 2021 Apr 1;13(14):16364-16373. Epub 2021 Apr 1.

College of Environmental Science and Engineering, Hunan University, Lushan South Road, Yuelu District, Changsha 410082, People's Republic of China.

It is important to find an effective way to enhance the photocatalytic efficiency of metal-organic frameworks. In this work, an organic supermolecule perylene diimide (PDI) semiconductor with a carboxyl terminal was added into the synthesis process of MIL-53(Fe) crystals. The PDI/MIL-53(Fe) (PM) composite photocatalyst was first obtained. The TC-H photodegradation rate of the most efficient 5PM was nearly 94.08% within 30 min, whose apparent reaction rate constant () is 4 times that of PDI and 33 times that of MIL-53(Fe), respectively. By investigation and characterization, it has been found that PDI nanofibers were dispersed and fixed in MIL-53(Fe) and bonded to each other by covalent bonds. The radical trap experiments and electron spin resonance analysis illustrated that hydroxyl radical (·OH), superoxide radical (·O), and photogenerated holes (h) were active species. Combined with the band structure of PDI and MIL-53(Fe), it is proposed that the PM photocatalyst was a Z-scheme heterojunction mechanism. Therefore, PM photocatalysts showed excellent charge separation and transfer ability. The performance improvement of 5PM is due to enhanced visible light absorption, efficient charge separation, and excellent redox potential. Five cyclic photocatalytic tests and experiments further demonstrate that the 5PM photocatalyst has a promising future for pollutant removal.
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http://dx.doi.org/10.1021/acsami.1c01308DOI Listing
April 2021

A Fast Spatial Pool Learning Algorithm of Hierarchical Temporal Memory Based on Minicolumn's Self-Nomination.

Comput Intell Neurosci 2021 17;2021:6680833. Epub 2021 Mar 17.

Department of Computer Science and Communication Engineering, Jiangsu University, Zhenjiang, China.

As a new type of artificial neural network model, HTM has become the focus of current research and application. The sparse distributed representation is the basis of the HTM model, but the existing spatial pool learning algorithms have high training time overhead and may cause the spatial pool to become unstable. To overcome these disadvantages, we propose a fast spatial pool learning algorithm of HTM based on minicolumn's nomination, where the minicolumns are selected according to the load-carrying capacity and the synapses are adjusted using compressed encoding. We have implemented the prototype of the algorithm and carried out experiments on three datasets. It is verified that the training time overhead of the proposed algorithm is almost unaffected by the encoding length, and the spatial pool becomes stable after fewer iterations of training. Moreover, the training of the new input does not affect the already trained results.
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http://dx.doi.org/10.1155/2021/6680833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994094PMC
March 2021

OXPHOS deficiency activates global adaptation pathways to maintain mitochondrial membrane potential.

EMBO Rep 2021 04 3;22(4):e51606. Epub 2021 Mar 3.

Graduate School of Peking Union Medical College, Beijing, China.

Reduction of mitochondrial membrane potential (Δψ ) is a hallmark of mitochondrial dysfunction. It activates adaptive responses in organisms from yeast to human to rewire metabolism, remove depolarized mitochondria, and degrade unimported precursor proteins. It remains unclear how cells maintain Δψ , which is critical for maintaining iron-sulfur cluster (ISC) synthesis, an indispensable function of mitochondria. Here, we show that yeast oxidative phosphorylation mutants deficient in complex III, IV, V, and mtDNA, respectively, exhibit activated stress responses and progressive reduction of Δψ . Extensive omics analyses of these mutants show that these mutants progressively activate adaptive responses, including transcriptional downregulation of ATP synthase inhibitor Inh1 and OXPHOS subunits, Puf3-mediated upregulation of import receptor Mia40 and global mitochondrial biogenesis, Snf1/AMPK-mediated upregulation of glycolysis and repression of ribosome biogenesis, and transcriptional upregulation of cytoplasmic chaperones. These adaptations disinhibit mitochondrial ATP hydrolysis, remodel mitochondrial proteome, and optimize ATP supply to mitochondria to convergently maintain Δψ , ISC biosynthesis, and cell proliferation.
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http://dx.doi.org/10.15252/embr.202051606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025004PMC
April 2021

Machine learning-based cytokine microarray digital immunoassay analysis.

Biosens Bioelectron 2021 May 20;180:113088. Epub 2021 Feb 20.

Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA; Michigan Center for Integrative Research in Critical Care, University of Michigan, Ann Arbor, MI, 48109, USA; Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI, 48109, USA. Electronic address:

Serial measurement of a large panel of protein biomarkers near the bedside could provide a promising pathway to transform the critical care of acutely ill patients. However, attaining the combination of high sensitivity and multiplexity with a short assay turnaround poses a formidable technological challenge. Here, the authors develop a rapid, accurate, and highly multiplexed microfluidic digital immunoassay by incorporating machine learning-based autonomous image analysis. The assay has achieved 12-plexed biomarker detection in sample volume <15 μL at concentrations < 5 pg/mL while only requiring a 5-min assay incubation, allowing for all processes from sampling to result to be completed within 40 min. The assay procedure applies both a spatial-spectral microfluidic encoding scheme and an image data analysis algorithm based on machine learning with a convolutional neural network (CNN) for pre-equilibrated single-molecule protein digital counting. This unique approach remarkably reduces errors facing the high-capacity multiplexing of digital immunoassay at low protein concentrations. Longitudinal data obtained for a panel of 12 serum cytokines in human patients receiving chimeric antigen receptor-T (CAR-T) cell therapy reveals the powerful biomarker profiling capability. The assay could also be deployed for near-real-time immune status monitoring of critically ill COVID-19 patients developing cytokine storm syndrome.
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http://dx.doi.org/10.1016/j.bios.2021.113088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896497PMC
May 2021

Novel MSX1 variants identified in families with nonsyndromic oligodontia.

Int J Oral Sci 2021 01 8;13(1). Epub 2021 Jan 8.

Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China.

The goal of this study was to identify MSX1 gene variants in multiple Chinese families with nonsyndromic oligodontia and analyse the functional influence of these variants. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variants in five families with nonsyndromic oligodontia, and a series of bioinformatics databases were used for variant confirmation and functional prediction. Phenotypic characterization of the members of these families was described, and an in vitro analysis was performed for functional evaluation. Five novel MSX1 heterozygous variants were identified: three missense variants [c.662A>C (p.Q221P), c.670C>T (p.R224C), and c.809C>T (p.S270L)], one nonsense variant [c.364G>T (p.G122*)], and one frameshift variant [c.277delG (p.A93Rfs*67)]. Preliminary in vitro studies demonstrated that the subcellular localization of MSX1 was abnormal with the p.Q221P, p.R224C, p.G122*, and p.A93Rfs*67 variants compared to the wild type. Three variants (p.Q221P, p.G122*, and p.A93Rfs*67) were classified as pathogenic or likely pathogenic, while p.S270L and p.R224C were of uncertain significance in the current data. Moreover, we summarized and analysed the MSX1-related tooth agenesis positions and found that the type and variant locus were not related to the severity of tooth loss. Our results expand the variant spectrum of nonsyndromic oligodontia and provide valuable information for genetic counselling.
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http://dx.doi.org/10.1038/s41368-020-00106-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794556PMC
January 2021

Proteome-Wide Alterations of Asymmetric Arginine Dimethylation Associated With Pancreatic Ductal Adenocarcinoma Pathogenesis.

Front Cell Dev Biol 2020 3;8:545934. Epub 2020 Dec 3.

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

Arginine methylation catalyzed by protein arginine methyltransferases (PRMTs) performs essential roles in regulating cancer initiation and progression, but its implication in pancreatic ductal adenocarcinoma (PDAC) requires further elucidation. In this study, asymmetric dimethylarginine (ADMA)-containing peptides in PDAC cell line PANC-1 were identified by label-free quantitative proteomics combined with affinity purification, using human non-cancerous pancreatic ductal epithelium cell line HPDE6c7 as the control. In total, 289 ADMA sites in 201 proteins were identified in HPDE6c7 and PANC-1 cells, including 82 sites with lower dimethylation and 37 sites with higher dimethylation in PANC-1 cells compared with HPDE6c7 cells. These ADMA-containing peptides demonstrated significant enrichment of glycine and proline residues in both cell lines. Importantly, leucine residues were significantly enriched in ADMA-containing peptides identified only in HPDE6c7 cells or showing lower dimethylation in PANC-1 cells. ADMA-containing proteins were significantly enriched in multiple biological processes and signaling cascades associated with cancer development, such as spliceosome machinery, the Wnt/β-catenin, Hedgehog, tumor growth factor beta (TGF-β), and mitogen-activated protein kinase (MAPK) signaling pathways. Moreover, PDAC cell lines with enhanced cell viability showed lower PRMT4 protein abundance and global ADMA-containing protein levels compared with HPDE6c7. PRMT4 overexpression partially recovered ADMA-containing protein levels and repressed viability in PANC-1 cells. These results revealed significantly altered ADMA-containing protein profiles in human pancreatic carcinoma cells, which provided a basis for elucidating the pathogenic roles of PRMT-mediated protein methylation in pancreatic cancer.
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http://dx.doi.org/10.3389/fcell.2020.545934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744470PMC
December 2020

A Progressive Somatic Cell Niche Regulates Germline Cyst Differentiation in the Drosophila Ovary.

Curr Biol 2021 Feb 18;31(4):840-852.e5. Epub 2020 Dec 18.

National Institute of Biological Sciences, No. 7 Science Park Road, Zhongguancun Life Science Park, Beijing 102206, China; Tsinghua Institute of Multidisciplinary Biomedical Research, Tsinghua University, Beijing 102206, China. Electronic address:

In the germarium of the Drosophila ovary, developing germline cysts are surrounded by a population of somatic escort cells that are known to function as the niche cells for germline differentiation; however, the underlying molecular mechanisms of this niche function remain poorly understood. Through single-cell gene expression profiling combined with genetic analyses, we here demonstrate that the escort cells can be spatially and functionally divided into two successive domains. The anterior escort cells (aECs) specifically produce ecdysone, which acts on the cystoblast to promote synchronous cell division, whereas the posterior escort cells (pECs) respond to ecdysone signaling and regulate soma-germline cell adhesion to promote the transition from 16-cell cyst-to-egg chamber formation. The patterning of the aEC and pEC domains is independent of the germline but is dependent on JAK/STAT signaling activity, which emanates from the posterior. Thus, a heterogeneous population of escort cells constitutes a stepwise niche environment to orchestrate cystoblast division and differentiation toward egg chamber formation.
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http://dx.doi.org/10.1016/j.cub.2020.11.053DOI Listing
February 2021

Retrospective Clinical Evaluation of Negative-Pressure Wound Therapy for Infection Prevention Following Malignant Pelvic Bone Tumor Resection Reconstruction.

Adv Skin Wound Care 2021 Jan;34(1):1-6

At the Tenth People's Hospital affiliated with Tongji University, Tongji University School of Medicine, in Shanghai, China, Tao Cai, MD, is a resident physician; Lei Zhang, MD, is an attending physician; Kunpeng Zhu, MD, is a physician; Jianping Hu, MD, is a physician; Taichen Zhan, MD, is a physician; Liwei Liu, MD, is an anesthetist; Cheng Li, MD, is an anesthetist; and Chunlin Zhang, MD, is a professor. Acknowledgments: The results of this project were previously reported at the 19th conference of the International Society of Limb Salvage, Osaka, Japan.

Objective: To evaluate the clinical outcomes of negative-pressure wound therapy (NPWT) for infection prevention following pelvic reconstruction after malignant bone tumor resection.

Methods: The study involved 82 patients who underwent pelvic reconstruction following en-bloc resection of malignant bone tumors between January 2003 and January 2016. Forty patients were treated with NPWT via implantation of vacuum-sealing drainage (VSD) materials into the pelvic cavity to prevent infection and wound problems (VSD group), and the remaining 42 patients underwent conventional treatment (control group). Study authors compared the inpatient length of stay, antibiotic use, drainage volume, time to wound closure, and infection rates between groups. Investigators also conducted cell cultures of the wound cavity washing fluid and hematoxylin-eosin staining for VSD materials to find recurrent tumor cells.

Results: In the VSD group, one patient (2.5%) had a superficial wound problem. In the control group, 18 patients (42.9%) had deep infection or wound problems. The VSD group had a significantly decreased infection rate, duration of antibiotic administration and inpatient stay, as well as increased wound healing compared with the control group (P < .05). Further, no tumor cells were observed in the VSD material or the wound cavity washing fluid.

Conclusions: The application of NPWT with VSD material may be an effective and reliable method for preventing infection in patients who undergo pelvic reconstruction following malignant tumor resection.
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http://dx.doi.org/10.1097/01.ASW.0000723280.71047.73DOI Listing
January 2021

Rapid removal of organic pollutants by a novel persulfate/brochantite system: Mechanism and implication.

J Colloid Interface Sci 2021 Mar 8;585:400-407. Epub 2020 Dec 8.

College of Environmental Science and Engineering, Hunan University, Lushan South Road, Yuelu District, Changsha 410082, PR China; Key Laboratory of Environmental Biology and Pollution Control (Hunan University), Ministry of Education, Lushan South Road, Yuelu District, Changsha 410082, PR China.

Using natural minerals as persulfate activators can develop effective and economical in situ chemical oxidation technology for environmental remediation. Yet, few natural minerals can provide a high activation efficiency. Here, we demonstrate that brochantite (CuSO(OH)), a natural mineral, can be used as a persulfate activator for the rapid degradation of tetracycline hydrochloride (TC-H). Approximately 70% of TC-H was removed in CuSO(OH)/PDS within 5 min, which much higher than that of CuP (61.99%), CuO (29.75%), CNT (25.83%), FeO, (14.48%) and MnO (9.76%). Experiments and theoretical calculations suggested that surface copper acts as active sites induce the production of free radicals. The synergistic effect of Cu/S promotes the cycle between Cu/Cu. Sulfate radicals and hydroxyl radicals are the main reactive oxygen species that are responsible for the rapid removal of TC-H. The findings of this work show a novel persulfate/brochantite system and provide useful information for the environmental remediation.
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http://dx.doi.org/10.1016/j.jcis.2020.11.106DOI Listing
March 2021

Cascade Radical Annulation of 2-Alkynylthio(seleno)anisoles with Acetone or Acetonitrile: Synthesis of 3-Acetomethyl- or Cyanomethyl-Substituted Benzothio(seleno)phenes.

J Org Chem 2021 Jan 7;86(1):1002-1011. Epub 2020 Dec 7.

Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China.

An efficient method for the direct preparation of 3-aceto(cyano)methyl-substituted benzothio(seleno)phenes has been achieved through C(sp)-H bond activation of easily available acetone or acetonitrile and cascade radical cyclization reaction. In this cascade radical cyclization reaction, C(sp)-C(sp) and C(sp)-S bonds, as well as benzenethio(seleno)phene skeletons, can be built along with the cleavage of the C(sp)-S bond, demonstrating the high step-economics and efficiency of this approach.
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http://dx.doi.org/10.1021/acs.joc.0c02444DOI Listing
January 2021

Association Between Serum IgG Concentrations and Prognosis in IgA Nephropathy.

Iran J Kidney Dis 2020 Dec;14(6):454-462

Department of Nephrology, Shenzhen Second People's Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen 518037, China.

Introduction: To investigate the relationship between serum IgG (sIgG) concentration and the prognosis of IgA nephropathy (IgAN).

Methods: A total of 309 patients with biopsy-proven IgAN in the Second Referral Hospital of Shenzhen were enrolled between 2010/01 and 2017/06. Patients were divided into 3 groups on the basis of sIgG tertiles: < 8.99 g/L (Group G1), 8.99 to 11.17 g/L (Group G2), and > 11.17 g/L (Group G3).

Results: As the level of sIgG increased, there was a decrease in DBP, serum creatinine, 24h urine proteinuria and an increase in serum albumin (all P < .05). In terms of pathological manifestations, with increasing sIgG levels, there was a tendency of decline in the Lee's grading system or high-grade tubular atrophy/interstitial fibrosis or in the proportion of glomerular sclerosis and the ratio of crescent (all P < .05). Kaplan-Meier analysis indicated that the cumulative renal survivals rates were significantly higher in patients with elevated sIgG (P < .05). Cox regression analysis showed that after adjusting for gender, age, BMI, and clinical indicators (BP, 24h urine proteinuria, eGFR, M, E, S, T, and the ratio of crescent), decreased sIgG level at the time of renal biopsy is an independent risk factor for unfavorable outcomes in IgAN. Furthmore, every 1 g/L decrease in sIgG level was associated with a 1.74-fold (95% CI: 1.30 to 5.38) increased risk of the incidence of composite renal outcomes.

Conclusions: Decreased serum IgG level at baseline might be a kind of predictive marker for the poor prognosis of IgAN.
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December 2020

A New Embedded Key-Value Store for NVM Device Simulator.

Micromachines (Basel) 2020 Dec 2;11(12). Epub 2020 Dec 2.

The School of Computer Science, Communication Engineering of Jiangsu University, Zhenjiang 212013, China.

The non-volatile memory (NVM) device is a useful way to solve the memory wall in computers. However, the current I/O software stack in operating systems becomes a performance bottleneck for applications based on NVM devices, especially for key-value stores. We analyzed the characteristics of key-value stores and NVM devices and designed a new embedded key-value store for an NVM device simulator named PMEKV. The embedded processor in NVM devices was used to manage key-value pairs to reduce the data transfer between NVM devices and key-value applications. Meanwhile, it also cut down the data copy between the user space and the kernel space in the operating system to alleviate the I/O software stacks on the efficiency of key-value stores. The architecture, data layout, management strategy, new interface and log strategy of PMEKV are given. Finally, a prototype of PMEKV was implemented based on PMEM. We used YCSB to test and compare it with Redis, MongDB, and Memcache. Meanwhile, the Redis for PMEM named PMEM-Redis and PMEM-KV were also used to test and compared with PMEKV. The results show that PMEKV had the advantage of throughput and adaptability compared with the current key-value stores.
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http://dx.doi.org/10.3390/mi11121075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7761609PMC
December 2020

Rapid single-molecule digital detection of protein biomarkers for continuous monitoring of systemic immune disorders.

Blood 2021 Mar;137(12):1591-1602

Department of Mechanical Engineering.

Digital protein assays have great potential to advance immunodiagnostics because of their single-molecule sensitivity, high precision, and robust measurements. However, translating digital protein assays to acute clinical care has been challenging because it requires deployment of these assays with a rapid turnaround. Herein, we present a technology platform for ultrafast digital protein biomarker detection by using single-molecule counting of immune-complex formation events at an early, pre-equilibrium state. This method, which we term "pre-equilibrium digital enzyme-linked immunosorbent assay" (PEdELISA), can quantify a multiplexed panel of protein biomarkers in 10 µL of serum within an unprecedented assay incubation time of 15 to 300 seconds over a 104 dynamic range. PEdELISA allowed us to perform rapid monitoring of protein biomarkers in patients manifesting post-chimeric antigen receptor T-cell therapy cytokine release syndrome, with ∼30-minute sample-to-answer time and a sub-picograms per mL limit of detection. The rapid, sensitive, and low-input volume biomarker quantification enabled by PEdELISA is broadly applicable to timely monitoring of acute disease, potentially enabling more personalized treatment.
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http://dx.doi.org/10.1182/blood.2019004399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065241PMC
March 2021

A digital protein microarray for COVID-19 cytokine storm monitoring.

Lab Chip 2021 01 19;21(2):331-343. Epub 2020 Nov 19.

Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.

Despite widespread concern regarding cytokine storms leading to severe morbidity in COVID-19, rapid cytokine assays are not routinely available for monitoring critically ill patients. We report the clinical application of a digital protein microarray platform for rapid multiplex quantification of cytokines from critically ill COVID-19 patients admitted to the intensive care unit (ICU) at the University of Michigan Hospital. The platform comprises two low-cost modules: (i) a semi-automated fluidic dispensing/mixing module that can be operated inside a biosafety cabinet to minimize the exposure of the technician to the virus infection and (ii) a 12-12-15 inch compact fluorescence optical scanner for the potential near-bedside readout. The platform enabled daily cytokine analysis in clinical practice with high sensitivity (<0.4 pg mL), inter-assay repeatability (∼10% CV), and rapid operation providing feedback on the progress of therapy within 4 hours. This test allowed us to perform serial monitoring of two critically ill patients with respiratory failure and to support immunomodulatory therapy using the selective cytopheretic device (SCD). We also observed clear interleukin-6 (IL-6) elevations after receiving tocilizumab (IL-6 inhibitor) while significant cytokine profile variability exists across all critically ill COVID-19 patients and to discover a weak correlation between IL-6 to clinical biomarkers, such as ferritin and C-reactive protein (CRP). Our data revealed large subject-to-subject variability in patients' response to COVID-19, reaffirming the need for a personalized strategy guided by rapid cytokine assays.
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http://dx.doi.org/10.1039/d0lc00678eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855944PMC
January 2021

Selenium-doped calcium phosphate biomineral reverses multidrug resistance to enhance bone tumor chemotherapy.

Nanomedicine 2021 02 10;32:102322. Epub 2020 Nov 10.

Department of Orthopaedic Surgery, Institute of Bone Tumor, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, PR China. Electronic address:

The construction of a functional drug delivery system to reverse the multidrug resistance (MDR) of bone tumors in cases of failed chemotherapy remains a challenge. Herein, we demonstrate a selenium-doped calcium phosphate (Se-CaP) biomineral with high biocompatibility, biodegradability and pH-sensitive drug release properties. Se-CaP may not only serve as an effective drug-carrier to enhance the uptake of doxorubicin (DOX), but may also synchronously induce caspases-mediated apoptosis of osteosarcoma by generating intracellular reactive oxygen species (ROS). Furthermore, in vitro and in vivo studies obviously demonstrate that Se-CaP can reverse the MDR of osteosarcoma by down-regulating the expression of MDR-related ABC (ATP binding cassette) transporters proteins (ABCB1 and ABCC1). Finally, DOX-loaded Se-CaP can significantly inhibit DOX-resistant MG63 (MG63/DXR) tumor growth in nude mice. Considering its biomimetic chemical properties, the Se-CaP biomineral, with the multiple functions mentioned above, could be a promising candidate for treating bone tumors with MDR characteristics.
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http://dx.doi.org/10.1016/j.nano.2020.102322DOI Listing
February 2021

Down-regulated expression of transient receptor potential ankyrin 1 in lichen simplex chronicus.

Ann Palliat Med 2020 Nov 10;9(6):3757-3765. Epub 2020 Nov 10.

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: Lichen simplex chronicus (LSC) is an acquired chronic dermatosis that is often accompanied by severe paroxysmal pruritus, and its pathogenesis to date is still unclear. Transient receptor potential channel A1 (TRPA1) is a non-selective cation channel. TRPA1 is widely expressed in skin, sensory neurons, and various other tissues, along with various biological functions and activation mechanisms. This study aimed to explore the changes in TRPA1 expression in human LSC and provide evidence for further research on the role of TRPA1 in chronic pruritus.

Methods: A total of 21 skin lesion specimens from LSC patients with skin pruritus lasting more than 6 weeks, and 28 normal skin tissue specimens through the skin biopsy from June 2018 to February 2019 were collected. The expression of TRPA1 in these skin tissues was evaluated through western blotting, quantitative reverse transcription PCR (qRT-PCR), and immunohistochemical analysis. The changes of inflammatory mediators, including interleukin (IL)-6, IL-13, endothelin-1 (ET-1), and thymic stromal lymphopoietin (TSLP), as well as substance P, are also analyzed by qRT-PCR. TRPA1 was detected using immunohistochemistry for all skin layers, the basal layer, and around the blood vessels of the dermis.

Results: The expression of TRPA1 in LSC specimens was significantly decreased as compared with that in the normal specimens (P<0.05). Also, TRPA1 protein levels were consistently decreased in LSC specimens (P<0.05). Simultaneously, the mRNA expressions of TRPA1, IL-6, IL-13, ET-1, TSLP, and substance P presented with no significant differences between LSC and normal specimens.

Conclusions: TRPA1 expression is proved downregulated in skin lesions of LSC patients with skin pruritus, indicating that TRPA1 serves as a crucial role in the pathogenesis of human LSC.
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http://dx.doi.org/10.21037/apm-20-1712DOI Listing
November 2020

Synthesis of Ligustrazine from Acetaldehyde by a Combined Biological-Chemical Approach.

ACS Synth Biol 2020 11 6;9(11):2902-2908. Epub 2020 Nov 6.

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.

Ligustrazine is an important active alkaloid in medicine and in the food industry. Here, we developed a combined biological-chemical approach to produce ligustrazine from acetaldehyde. First, we constructed a whole-cell biocatalytic system to produce the precursor acetoin from acetaldehyde by overexpressing formolase (FLS). Second, a two-step strategy was developed to enhance protein expression of FLS by codon usage optimization at the first 14 codons and the introduction of an overlapping gene before the start codon. Through expression optimization and directed evolution of FLS, we improved the titer of acetoin about 40 fold when the concentration of acetaldehyde was 1.5 M. Finally, after reaction conditions optimization, the titer of acetoin and ligustrazine reached 222 g L and 94 g L, with a 86.5% and 48% conversion rate from acetaldehyde, respectively. The developed one-pot synthesis for acetoin and ligustrazine is expected to be applied to industrial production in the future with the advantages of a green process, high efficiency, and low cost.
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http://dx.doi.org/10.1021/acssynbio.0c00113DOI Listing
November 2020

Mitigating NO emissions from an ammonia-fueled micro-power system with a perforated plate implemented.

J Hazard Mater 2021 Jan 6;401:123848. Epub 2020 Sep 6.

School of Aerospace Engineering, Beijing Institute of Technology, Beijing, 100083, China.

In this work, three-dimensional numerical simulations with a simplified reaction mechanism are conducted to investigate the effect of implementing a perforated plate in an ammonia-fueled micro-power systems on the NO emission behavior. Detailed analyses on 1) the perforated plate hole dimensionless width w, dimensionless location l as well as the material property are performed. Results show that with an optimized perforated plate implemented, the NO emission is reduced by up to 73.3 % compared to those in the absence of perforated plates. The decrease is mainly due to the formation of a recirculation zone with a low flame temperature. Increasing w is shown to play a positive role in minimizing the NO generation, while l leads to a reverse trend resulting from the size variation of the recirculation zone. In contrast, the plate material has a negligible effect on NO emissions. It is also shown that the pressure loss P is varied non-monotonically with l, but monotonically with w and the NH volumetric flow rate. Furthermore, the conjugate heat transfer between the plate and combustion products has a certain impact on P. The present work shed lights on reducing NO emissions by implementing a well-designed perforated plate for practical micro-power systems.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123848DOI Listing
January 2021

LINC00210 exerts oncogenic roles in glioma by sponging miR-328.

Exp Ther Med 2020 Dec 2;20(6):137. Epub 2020 Oct 2.

Department of Neurosurgery, Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.

Long non-coding RNAs (lncRNAs) have been reported to serve key roles in human cancer types, including glioma. However, to the best of our knowledge, the expression and function of lncRNA LINC00210 in glioma have not previously been investigated. The present study was conducted to explore the regulatory role of LINC00210 in glioma cells. The present study demonstrated that LINC00210 was significantly upregulated in glioma tissues, and high expression of LINC00210 was significantly associated with advanced clinical stage and poor prognosis in patients with glioma. It was found that LINC00210 knockdown significantly inhibited the proliferation and migration of U251 and T98G cells. The results of luciferase reporter assays indicated that LINC00210 could directly target microRNA (miR)-328 in glioma cells, and miR-328 expression was negatively correlated with LINC00210 expression in glioma tissues. LINC00210 knockdown significantly promoted the expression of miR-328 in U251 and T98G cells. Moreover, silencing miR-328 impaired the inhibitory effects of LINC00210 knockdown on the proliferation and migration of U251 and T98G cells. Therefore, the present results suggested that LINC00210 may exert an oncogenic role in glioma via sponging miR-328.
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http://dx.doi.org/10.3892/etm.2020.9266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581018PMC
December 2020

Functional study of novel PAX9 variants: The paired domain and non-syndromic oligodontia.

Oral Dis 2020 Oct 20. Epub 2020 Oct 20.

Department of Prosthodontics, Peking University School and Hospital of Stomatology and National Clinical Research Centre for Oral Diseases and National Engineering Laboratory for Digital and Material Technology of Stomatology and Beijing Key Laboratory of Digital Stomatology, Beijing, China.

Objectives: To investigate pathogenic variants of the paired box 9 (PAX9) gene in patients with non-syndromic oligodontia, and the functional impact of these variants.

Subjects And Methods: Whole exome sequencing and Sanger sequencing were utilized to detect gene variants in a cohort of 80 patients diagnosed with non-syndromic oligodontia. Bioinformatic and conformational analyses, fluorescence microscopy and luciferase reporter assay were employed to explore the functional impact.

Results: We identified three novel variants in the PAX9, including two frameshift variants (c.211_212insA; p.I71Nfs*246 and c.236_237insAC; p.T80Lfs*6), and one missense variant (c.229C > G; p.R77G). Familial co-segregation verified an autosomal-dominant inheritance pattern. Conformational analyses revealed that the variants resided in the paired domain, and could cause corresponding structural impairment of the PAX9 protein. Fluorescence microscopy showed abnormal subcellular localizations of frameshift variants, and luciferase assay showed impaired downstream transactivation activities of the bone morphogenetic protein 4 (BMP4) gene in all variants.

Conclusions: Our findings broaden the spectrum of PAX9 variants in patients with non-syndromic oligodontia and support that paired domain structural impairment and the dominant-negative effect are likely the underlying mechanisms of PAX9-related non-syndromic oligodontia. Our findings will facilitate genetic diagnosis and counselling, and help lay the foundation for precise oral health therapies.
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http://dx.doi.org/10.1111/odi.13684DOI Listing
October 2020

Comparative analysis of rare EDAR mutations and tooth agenesis pattern in EDAR- and EDA-associated nonsyndromic oligodontia.

Hum Mutat 2020 11 16;41(11):1957-1966. Epub 2020 Sep 16.

Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Clinical Research Center for Oral Diseases, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China.

Nonsyndromic oligodontia is a rare congenital anomaly. Mutations in the ectodysplasin A receptor (EDAR) gene are the primary cause of hypohidrotic ectodermal dysplasia but are rarely reported in nonsyndromic oligodontia. This study investigated EDAR mutations in multiplex nonsyndromic oligodontia and comparatively analyzed the EDAR- and EDA-related tooth agenesis patterns. Mutation screening was carried out using whole-exome sequencing and familial segregation. Evolutionary conservation and conformational analyses were used to evaluate the potential pathogenic influence of EDAR mutants. EDAR mutations were found to occur in 10.7% of nonsyndromic oligodontia cases. We reported seven heterozygous mutations of EDAR, including five novel mutations (c.404G>A, c.871G>A, c.43G>A, c.1072C>T, and c.1109T>C) and two known mutations (c.319A>G and c.1138A>C). Genotype-phenotype correlation analysis demonstrated that the EDAR-related tooth agenesis pattern was markedly different from EDA. The mandibular second premolars were most frequently missing (57.69%) in EDAR-mutated patients. Our results provide new evidence for the genotypic study of nonsyndromic oligodontia and suggest that EDAR haploinsufficiency results in nonsyndromic tooth agenesis. Furthermore, the distinct pattern between EDAR- and EDA-related tooth agenesis can be used as a guide for mutation screening during the clinical genetic diagnosis of this genetic disorder.
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http://dx.doi.org/10.1002/humu.24104DOI Listing
November 2020

Is increased symptom interval associated with advanced stage and poorer outcome? A prospective multicenter study of 220 patients with osteosarcoma around the knee.

Cancer Epidemiol 2020 08 6;67:101776. Epub 2020 Jul 6.

Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Objective: Osteosarcoma is rare disease and there is a strong controversy about the potential impact of symptom interval on the stage of disease and patients' outcomes. We want to assess whether increased symptom interval (SI) is associated with advanced tumor stage and poor prognosis for patients with osteosarcoma.

Methods: We analyzed prospectively collected data of 220 patients younger than 40 years who had osteosarcoma around the knee. Symptom interval was analyzed to evaluate its impact on metastases at diagnosis, tumor volume, chemotherapy response and overall survival.

Results: The median of SI was 64.5 (Q1-Q3: 42-88) days. The 5-year overall survival rate for patients with different length of symptom interval (<42 days, 42-64 days, 65-87 days, > = 88 days) were 0.78 (95 %CI: 0.67-0.89), 0.49 (95 %CI: 0.35-0.63), 0.52 (95 %CI:0.39-0.65), and 0.65 (95 %CI:0.53-0.77) respectively(p = 0.013). Nonparametric test showed increased SI was associated with metastases at diagnosis (p = 0.008), but not associated with large tumor volume or poor chemotherapy response. Cox regression mode test showed that patient with increased SI had higher hazard ratio (42-64 days HR: 2.586 (95 %CI:1.360-4.915); 65-87 days, HR: 2.225 (95 %CI:1.170-4.233)) for poor outcomes compared to short SI (<42 days), though it was not significant in multivariate analysis (p = 0.182).

Conclusion: Increased SI but not the longest SI is associated with higher incidence of metastases at diagnosis; patients can benefit from an earlier diagnosis in terms of survival.
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http://dx.doi.org/10.1016/j.canep.2020.101776DOI Listing
August 2020

A Digital Protein Microarray for COVID-19 Cytokine Storm Monitoring.

medRxiv 2020 Jun 17. Epub 2020 Jun 17.

Despite widespread concern for cytokine storms leading to severe morbidity in COVID-19, rapid cytokine assays are not routinely available for monitoring critically ill patients. We report the clinical application of a machine learning-based digital protein microarray platform for rapid multiplex quantification of cytokines from critically ill COVID-19 patients admitted to the intensive care unit (ICU) at the University of Michigan Hospital. The platform comprises two low-cost modules: (i) a semi-automated fluidic dispensing/mixing module that can be operated inside a biosafety cabinet to minimize the exposure of technician to the virus infection and (ii) a 12-12-15 inch compact fluorescence optical scanner for the potential near-bedside readout. The platform enabled daily cytokine analysis in clinical practice with high sensitivity (<0.4pg/mL), inter-assay repeatability (~10% CV), and near-real-time operation with a 10 min assay incubation. A cytokine profiling test with the platform allowed us to observe clear interleukin-6 (IL-6) elevations after receiving tocilizumab (IL-6 inhibitor) while significant cytokine profile variability exists across all critically ill COVID-19 patients and to discover a weak correlation between IL-6 to clinical biomarkers, such as Ferritin and CRP. Our data revealed large subject-to-subject variability in a patient's response to anti-inflammatory treatment for COVID-19, reaffirming the need for a personalized strategy guided by rapid cytokine assays.
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http://dx.doi.org/10.1101/2020.06.15.20131870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310633PMC
June 2020