Publications by authors named "Zhi Huang"

397 Publications

A graph neural network model to estimate cell-wise metabolic flux using single-cell RNA-seq data.

Genome Res 2021 Jul 22. Epub 2021 Jul 22.

Indiana University;

The metabolic heterogeneity, and metabolic interplay between cells have been known as significant contributors to disease treatment resistance. However, with the lack of a mature high-throughput single-cell metabolomics technology, we have yet to establish systematic understanding of the intra-tissue metabolic heterogeneity and cooperative mechanisms. To mitigate this knowledge gap, we developed a novel computational method, namely scFEA (single-cell Flux Estimation Analysis), to infer cell-wise fluxome from single-cell RNA-sequencing (scRNA-seq) data. scFEA is empowered by a systematically reconstructed human metabolic map as a factor graph, a novel probabilistic model to leverage the flux balance constraints on scRNA-seq data, and a novel graph neural network based optimization solver. The intricate information cascade from transcriptome to metabolome was captured using multi-layer neural networks to capitulate the nonlinear dependency between enzymatic gene expressions and reaction rates. We experimentally validated scFEA by generating an scRNA-seq dataset with matched metabolomics data on cells of perturbed oxygen and genetic conditions. Application of scFEA on this dataset demonstrated the consistency between predicted flux and the observed variation of metabolite abundance in the matched metabolomics data. We also applied scFEA on five publicly available scRNA-seq and spatial transcriptomics datasets and identified context and cell group-specific metabolic variations. The cell-wise fluxome predicted by scFEA empowers a series of downstream analysis including identification of metabolic modules or cell groups that share common metabolic variations, sensitivity evaluation of enzymes with regards to their impact on the whole metabolic flux, and inference of cell-tissue and cell-cell metabolic communications.
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http://dx.doi.org/10.1101/gr.271205.120DOI Listing
July 2021

Weakly Supervised Deep Ordinal Cox Model for Survival Prediction from Whole-slide Pathological Images.

IEEE Trans Med Imaging 2021 Jul 15;PP. Epub 2021 Jul 15.

Whole-Slide Histopathology Image (WSI) is generally considered the gold standard for cancer diagnosis and prognosis. Given the large inter-operator variation among pathologists, there is an imperative need to develop machine learning models based on WSIs for consistently predicting patient prognosis. The existing WSI-based prediction methods do not utilize the ordinal ranking loss to train the prognosis model, and thus cannot model the strong ordinal information among different patients in an efficient way. Another challenge is that a WSI is of large size (e.g., 100,000-by-100,000 pixels) with heterogeneous patterns but often only annotated with a single WSI-level label, which further complicates the training process. To address these challenges, we consider the ordinal characteristic of the survival process by adding a ranking-based regularization term on the Cox model and propose a weakly supervised deep ordinal Cox model (BDOCOX) for survival prediction from WSIs. Here, we generate amounts of bags from WSIs, and each bag is comprised of the image patches representing the heterogeneous patterns of WSIs, which is assumed to match the WSI-level labels for training the proposed model. The effectiveness of the proposed method is well validated by theoretical analysis as well as the prognosis and patient stratification results on three cancer datasets from The Cancer Genome Atlas (TCGA).
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http://dx.doi.org/10.1109/TMI.2021.3097319DOI Listing
July 2021

Extraction and characterization of a functional protein from Champ. leaf.

Nat Prod Res 2021 Jul 2:1-8. Epub 2021 Jul 2.

Laboratory of Applied Biocatalysis, School of Food Science and Engineering, South China University of Technology, Guangzhou, China.

Natural plant-derived protein with excellent bioactivities has attracted much attention so a functional protein with molecular weight of 15.2 kDa was extracted from Champ. leaf for the first time. Under the pH of 12.0, solid-liquid ratio of 1:40 (w/v), extraction time of 2.0 h, and extraction temperature of 50 °C, the highest extracting efficiency (79.25 ± 0.78%) of the Champ. leaf protein (MLP) was achieved. The main structure of MLP contained β-fold and β-corner by Fourier transform infrared spectroscopy (FTIR) and Circular dichroism (CD) spectra analysis. Additionally, MLP was predominant with glutamic acid, aspartic acid, and leucine, which could be considered as a high quality natural protein. MLP showed great water holding capacity (WHC), oil absorption capacity (OAC), as well as emulsifying and foaming properties. Simultaneously, MLP exhibited considerable antioxidant activity. These results suggested that MLP could be utilised as a promising ingredient of functional foods.
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http://dx.doi.org/10.1080/14786419.2021.1947271DOI Listing
July 2021

Inhibiting DNA-PK induces glioma stem cell differentiation and sensitizes glioblastoma to radiation in mice.

Sci Transl Med 2021 06;13(600)

Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.

Glioblastoma (GBM), a lethal primary brain tumor, contains glioma stem cells (GSCs) that promote malignant progression and therapeutic resistance. SOX2 is a core transcription factor that maintains the properties of stem cells, including GSCs, but mechanisms associated with posttranslational SOX2 regulation in GSCs remain elusive. Here, we report that DNA-dependent protein kinase (DNA-PK) governs SOX2 stability through phosphorylation, resulting in GSC maintenance. Mass spectrometric analyses of SOX2-binding proteins showed that DNA-PK interacted with SOX2 in GSCs. The DNA-PK catalytic subunit (DNA-PKcs) was preferentially expressed in GSCs compared to matched non-stem cell tumor cells (NSTCs) isolated from patient-derived GBM xenografts. DNA-PKcs phosphorylated human SOX2 at S251, which stabilized SOX2 by preventing WWP2-mediated ubiquitination, thus promoting GSC maintenance. We then demonstrated that when the nuclear DNA of GSCs either in vitro or in GBM xenografts in mice was damaged by irradiation or treatment with etoposide, the DNA-PK complex dissociated from SOX2, which then interacted with WWP2, leading to SOX2 degradation and GSC differentiation. These results suggest that DNA-PKcs-mediated phosphorylation of S251 was critical for SOX2 stabilization and GSC maintenance. Pharmacological inhibition of DNA-PKcs with the DNA-PKcs inhibitor NU7441 reduced GSC tumorsphere formation in vitro and impaired growth of intracranial human GBM xenografts in mice as well as sensitized the GBM xenografts to radiotherapy. Our findings suggest that DNA-PK maintains GSCs in a stem cell state and that DNA damage triggers GSC differentiation through precise regulation of SOX2 stability, highlighting that DNA-PKcs has potential as a therapeutic target in glioblastoma.
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http://dx.doi.org/10.1126/scitranslmed.abc7275DOI Listing
June 2021

Effectiveness of sharp recanalization of superior vena cava-right atrium junction occlusion.

World J Clin Cases 2021 Jun;9(16):3848-3857

Department of Interventional Radiology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550000, Guizhou Province, China.

Background: Conventional recanalization techniques may fail in patients with completely occluded superior vena cava (SVC).

Aim: To analyze the effectiveness and complications of sharp recanalization for completely occluded SVC.

Methods: This was a retrospective study of patients that underwent puncture and recanalization of the SVC between January 2016 and December 2017 at our hospital. Sharp recanalization was performed using the RUPS-100 system. The patients were followed for 12 mo. The main outcomes were the patency rate of SVC and arteriovenous fistula flow during dialysis.

Results: The procedure was successful in all 14 patients (100%). Blood pressure in the distal SVC decreased in all 14 cases (100%) from 26.4 ± 2.7 cmHO to 14.7 ± 1.3 cmHO ( < 0.05). The first patency rates of the SVC at 24 h and at 3, 6, 9 and 12 mo after sharp recanalization were 100%, 92.9%, 85.7%, 78.6% and 71.4%, respectively. There were two (14.3%) severe, one (7.1%) moderate and one (7.1%) minor complication. The severe complications included one case of pericardial tamponade and one case of hemothorax.

Conclusion: The results suggest that sharp recanalization can be an additional tool to extend or renew the use of an occluded upper extremity access for hemodialysis. This could be of use in patients with long-term maintenance hemodialysis in whom the maintenance of central venous access is often a challenge.
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http://dx.doi.org/10.12998/wjcc.v9.i16.3848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180228PMC
June 2021

Novel Bisubstrate Inhibitors for Protein N-Terminal Acetyltransferase D.

J Med Chem 2021 Jun 10;64(12):8263-8271. Epub 2021 Jun 10.

Department of Medicinal Chemistry and Molecular Pharmacology, Purdue Institute for Drug Discovery, Purdue University Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907, United States.

Protein N-terminal acetyltransferase D (NatD, NAA40) that specifically acetylates the alpha-N-terminus of histone H4 and H2A has been implicated in various diseases, but no inhibitor has been reported for this important enzyme. Based on the acetyl transfer mechanism of NatD, we designed and prepared a series of highly potent NatD bisubstrate inhibitors by covalently linking coenzyme A to different peptide substrates via an acetyl or propionyl spacer. The most potent bisubstrate inhibitor displayed an apparent value of 1.0 nM. Biochemical studies indicated that bisubstrate inhibitors are competitive to the peptide substrate and noncompetitive to the cofactor, suggesting that NatD undergoes an ordered Bi-Bi mechanism. We also demonstrated that these inhibitors are highly specific toward NatD, displaying about 1000-fold selectivity over other closely related acetyltransferases. High-resolution crystal structures of NatD bound to two of these inhibitors revealed the molecular basis for their selectivity and inhibition mechanism, providing a rational path for future inhibitor development.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00141DOI Listing
June 2021

MOGONET integrates multi-omics data using graph convolutional networks allowing patient classification and biomarker identification.

Nat Commun 2021 06 8;12(1):3445. Epub 2021 Jun 8.

Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA.

To fully utilize the advances in omics technologies and achieve a more comprehensive understanding of human diseases, novel computational methods are required for integrative analysis of multiple types of omics data. Here, we present a novel multi-omics integrative method named Multi-Omics Graph cOnvolutional NETworks (MOGONET) for biomedical classification. MOGONET jointly explores omics-specific learning and cross-omics correlation learning for effective multi-omics data classification. We demonstrate that MOGONET outperforms other state-of-the-art supervised multi-omics integrative analysis approaches from different biomedical classification applications using mRNA expression data, DNA methylation data, and microRNA expression data. Furthermore, MOGONET can identify important biomarkers from different omics data types related to the investigated biomedical problems.
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http://dx.doi.org/10.1038/s41467-021-23774-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187432PMC
June 2021

Combination of endothelial progenitor cells and BB-94 significantly alleviates brain damage in a mouse model of diabetic ischemic stroke.

Exp Ther Med 2021 Jul 21;22(1):789. Epub 2021 May 21.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, P.R. China.

Ischemic stroke is a complication of chronic macrovascular disease in type 2 diabetes. However, the pathogenesis of diabetic ischemic stroke has not yet been fully clarified. The aim of the present study was to investigate the underlying effects of endothelial progenitor cells (EPCs) and the matrix metalloproteinase inhibitor BB-94 on diabetic stroke. experiments were performed using oxygen-glucose deprivation/reoxygenation (OGD/R) model cells, established using HT22 mouse hippocampal cells. MTT assays and flow cytometry revealed that BB-94 prominently induced the proliferation of the OGD/R model cells and prevented their apoptosis. When EPCs and BB-94 were applied to the OGD/R model cells in combination, proliferation was further accelerated and oxidative damage was attenuated. experiments were also performed using a middle cerebral artery occlusion (MCAO) mouse model. The results of modified neurological severity scoring and oxidative stress marker analysis demonstrated that EPCs and BB-94 prominently alleviated cerebral ischemia/reperfusion injury in the MCAO model mice. Furthermore, reverse transcription-quantitative PCR and western blot assays revealed that EPCs in combination with BB-94 significantly downregulated the expression of matrix metalloproteinases (MMPs) and upregulated the expression of tissue inhibitor of metalloproteinases 1 in OGD/R cells and MCAO model mice. The results suggest that EPCs were successfully isolated and identified, and the OGD/R cell and MCAO mouse models were successfully established. They also indicate that EPCs alone or in combination with BB-94 may exert protective effects against ischemic stroke via the reduction of MMP expression.
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http://dx.doi.org/10.3892/etm.2021.10221DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145984PMC
July 2021

Reduced expression of MiR-125a-5p aggravates LPS-induced experimental acute kidney injury pathology by targeting TRAF6.

Life Sci 2021 May 25:119657. Epub 2021 May 25.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, People's Republic of China. Electronic address:

Aims: Patients with acute kidney injury (AKI) have higher mortality, and sepsis is among its main causes. MicroRNAs (miRNAs) are essential for regulating kidney function and could have curative potential. This study explored the possibility to treat AKI with miR-125a-5p and reveal the possible mechanism.

Materials And Methods: LPS-induced mouse model and LPS-induced RAW264.7 cell model of AKI were established and treated with miR-125a-5p mimics or inhibitors. Serum creatinine and blood urea were measured to evaluate kidney function. The pathological changes of kidney tissues were detected by H&E and PAS staining technique, and the infiltration of macrophages were observed by immunohistochemistry. RAW264.7 cell viability, TRAF6 and cytokines expressions under LPS stimulation were measured. The role and therapeutic potential of miR-125a-5p were verified in vivo and in vitro after given miR-125a-5p mimics or inhibitors.

Key Findings: LPS-induced mice had increasing serum creatinine and urea, and evident pathological changes, including severe tubular dilatation and macrophages infiltration. TRAF6 expression in the kidney was significantly higher, while miR-125a-5p expression was suppressed. MiR-125a-5p targeted TRAF6, and its overexpression deactivated NF-κB signaling pathway, reducing downstream TNF-α, IL-1β and IL-6 expressions. MiR-125a-5p mimics rescued LPS-induced kidney damage and suppressed pro-inflammatory cytokines expression through inhibiting TRAF6/NF-κB axis.

Significance: We highlighted that miR-125a-5p could inhibit LPS-induced acute inflammation in the kidney through targeting TRAF6/NF-κB axis. These results might contribute to the development of molecular therapy in AKI.
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http://dx.doi.org/10.1016/j.lfs.2021.119657DOI Listing
May 2021

miR-204 silencing reduces mitochondrial autophagy and ROS production in a murine AD model via the TRPML1-activated STAT3 pathway.

Mol Ther Nucleic Acids 2021 Jun 15;24:822-831. Epub 2021 Feb 15.

Department of Neurology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P.R. China.

Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD), whereby accumulation of damaged mitochondria in conjunction with impaired mitophagy contributes to neurodegeneration. Various non-transcribed microRNAs (miRNAs) are involved in this process. In the present study, we aimed to decipher the participation of miR-204 in a murine AD model. Primary hippocampal neurons were isolated from mice and treated with β-amyloid 1-42 (Aβ1-42) to establish a cell model of AD. Dichloro-dihydro-fluorescein diacetate and dihydrorhodamine 123 staining assays were performed to measure total reactive oxygen species (ROS) and mitochondrial ROS production in neurons, and MitoSOX staining was done to analyze mitochondrial ROS production in hippocampus. Furthermore, mitochondrial autophagy was observed in hippocampus from amyloid precursor protein/pesenilin-1 AD modeled mice, and their cognitive function was assessed by Morris water maze. Mitochondrial damage, ROS production, and mitochondrial autophagy were observed in AD cell model induced by Aβ1-42. In AD, signal transducer and activator of transcription 3 (STAT3) and transient receptor potential mucolipin-1 (TRPML1) expression was downregulated, although miR-204 expression was upregulated. TRPML1 overexpression, downregulation of miR-204, or STAT3 pathway activation reduced the Aβ1-42-induced mitochondrial damage, along with ROS production and mitochondrial autophagy and . Silencing of miR-204 could upregulate TRPML1 expression, thus suppressing ROS production and mitochondrial autophagy in AD through STAT3 pathway.
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http://dx.doi.org/10.1016/j.omtn.2021.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121631PMC
June 2021

miR-142-3p and HMGB1 Are Negatively Regulated in Proliferation, Apoptosis, Migration, and Autophagy of Cartilage Endplate Cells.

Cartilage 2021 May 6:19476035211012444. Epub 2021 May 6.

Surgical Department of Thoracolumbar, the Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia, China.

Background: Cartilage endplate (CEP) degeneration plays a vital role in the pathological process of intervertebral disc degeneration. It has been previously reported that microRNAs may participate in the occurrence and development of intervertebral disc degeneration through regulating its target genes directly. The regulatory roles of miR-142-3p/HMGB1 in some orthopedic diseases have been determined successively, but there was no report about the degeneration of CEP. Therefore, we aimed to determine the regulation of miR-142-3p/HMGB1 or potential molecular mechanisms on proliferation, apoptosis, migration, and autophagy of CEP cells.

Methods: The target gene of miR-142-3p was determined by double luciferase assay. We selected ATDC5 cell lines. CCK-8 method was used to detect cell proliferation. Real-time fluorescence quantitative polymerase chain reaction was used to determine gene expression levels, and western blot analysis was used to determine protein expression levels. We chose flow cytometry to measure cell apoptosis and cell cycle.

Results: The result of luciferase detection showed that the target gene of miR-142-3p in CEP cells was HMGB1. Knockdown of the miR-142-3p inhibited the expression level of HMGB1, the proliferation and migration of CEP cells, but it promoted apoptosis of CEP cells. In addition, the detection results of the proteins related to apoptosis or autophagy showed that knockdown of miR-142-3p promoted apoptosis and autophagy.

Conclusion: The negative regulation of miR-142-3p/HMGB1 can affect the proliferation, apoptosis, migration, and autophagy of CEP cells. Our results provide a new idea for the targeted treatment of CEP degeneration by inhibiting the expression of HMGB1.
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http://dx.doi.org/10.1177/19476035211012444DOI Listing
May 2021

Gene expression and DNA methylation analyses suggest that two immune related genes are prognostic factors of colorectal cancer.

BMC Med Genomics 2021 Apr 28;14(1):116. Epub 2021 Apr 28.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, China Agricultural University, Beijing, 100193, People's Republic of China.

Background: Colorectal cancer (CRC) is the second most prevalent cancer, as it accounts for approximately 10% of all annually diagnosed cancers. Studies have indicated that DNA methylation is involved in cancer genesis. The purpose of this study was to investigate the relationships among DNA methylation, gene expression and the tumor-immune microenvironment of CRC, and finally, to identify potential key genes related to immune cell infiltration in CRC.

Methods: In the present study, we used the ChAMP and DESeq2 packages, correlation analyses, and Cox regression analyses to identify immune-related differentially expressed genes (IR-DEGs) that were correlated with aberrant methylation and to construct a risk assessment model.

Results: Finally, we found that HSPA1A expression and CCRL2 expression were positively and negatively associated with the risk score of CRC, respectively. Patients in the high-risk group were more positively correlated with some types of tumor-infiltrating immune cells, whereas they were negatively correlated with other tumor-infiltrating immune cells. After the patients were regrouped according to the median risk score, we could more effectively distinguish them based on survival outcome, clinicopathological characteristics, specific tumor-immune infiltration status and highly expressed immune-related biomarkers.

Conclusion: This study suggested that the risk assessment model constructed by pairing immune-related differentially expressed genes correlated with aberrant DNA methylation could predict the outcome of CRC patients and might help to identify those patients who could benefit from antitumor immunotherapy.
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http://dx.doi.org/10.1186/s12920-021-00966-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080337PMC
April 2021

Associations between dietary patterns and anaemia in 6- to 23-month-old infants in central South China.

BMC Public Health 2021 04 9;21(1):699. Epub 2021 Apr 9.

Hunan University of Medicine, No. 492 Jinxi South Road, Huaihua, 418000, Hunan, China.

Background: Anaemia is prevalent in children. Therefore, this study examined the association between dietary patterns and anaemia among children in central South China.

Methods: Cross-sectional studies were conducted in Mayang, central South China, in 2015 and 2018. Diet data were collected using a questionnaire, and dietary patterns were identified via exploratory factor analysis. Haemoglobin was measured to assess anaemia status. Associations between dietary patterns and anaemia were assessed using a logistic regression model.

Results: The mean age of the infants surveyed was 14.06 months in 2015 and 16.58 months in 2018. Four dietary patterns were identified among infants aged 6-23 months: a diversified diet consisting mainly of tubers, dairy products, beans and bean products; a traditional diet consisting mainly of cereals, water, soup, vegetables and fruit; mainly breast milk, with a little powdered formula; or mainly multi-nutrient powders. The prevalence of anaemia in infants decreased from 29.49% in 2015 to 20.26% in 2018.In infants fed a diversified diet or multi-nutrient powders with top-quartile (Q4) scores, the risk of anaemia was reduced by 45%(adjusted odds ratio [AOR] = 0.55, 95%CI0.30-0.99, P = 0.047) or 59% (AOR = 0.41, 95% CI0.22-0.78, P = 0.006), respectively, compared to infants in the lowest quartile (Q1). Infants fed mainly breast milk had a 3.26-fold greater risk of anaemia compared to those with Q1 scores (AOR = 3.26, 95% CI 1.83-5.81, P < 0.001).

Conclusions: Four dietary patterns were identified among infants aged 6-23 months in central South China. Infants should be fed a variety of food groups to improve their anaemia status.
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http://dx.doi.org/10.1186/s12889-021-10699-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033660PMC
April 2021

MK801 regulates the expression of key osteoarthritis factors in osteoarthritis synovial fibroblasts through complement C5.

Res Vet Sci 2021 May 3;136:377-384. Epub 2021 Mar 3.

Department of Anesthesiology, Guizhou Medical University, Guiyang 550002, PR China. Electronic address:

Background: Osteoarthritis is currently one of the most common chronic diseases. As life expectancy increases, its prevalence and incidence are expected to rise. At present, more and more evidences prove the correlation between the complement system and osteoarthritis (OA). This study aims to investigate complement C5's influence on the effect of MK801 on osteoarthritis synovial fibroblasts (OA-SFs).

Methods: We used IL-1b to induce OA-SFs derived from mice to obtain OA-SFs. And we performed RT-PCR and Western Blot assays to evaluate the expression levels of associated mRNA and protein. The alteration of MAC expression on OA-SFs cell membrane was evaluated by immunofluorescence assay. The expression of related inflammatory factors of OA-SFs was evaluated by ELISA experiment.

Results: MK801 could significantly inhibit the expression of osteoarthritis (OA) marker factors, such as: membrane attack complex (MAC), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-13 (MMP13). Meanwhile, MK801 can significantly inhibit the expression of complement C5 (C5) in OA-SFs. Immunofluorescence assay showed that MAC expression on OA-SFs cell membrane was significantly inhibited by MK801. The nucleo-plasmic separation experiment demonstrated that MK801 could significantly inhibit the activation of Nuclear factor-κB (NF-κB) signaling pathway in OA-SFs. Futhermore, koncking down the expression of C5 reversed the inhibition MK801 on the expression of OA-SFs inflammatory factors.

Conclusions: These results illustrated two points: first, MK801 inhibited the generation of MAC and the release of inflammation factors in OA-SFs through C5; second: MK801 inhibited the activation of NF-κB signaling pathway in OA-SFs.
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http://dx.doi.org/10.1016/j.rvsc.2021.03.003DOI Listing
May 2021

Exploring the effects of formula feeding on infant immune development in China: A prospective cohort study.

Asia Pac J Clin Nutr 2021 ;30(1):104-112

Department of toxicology, Hunan Provincial Center for Disease Control and Prevention, Hunan, China. Email:

Background And Objectives: The worldwide exclusive breastfeeding rate is suboptimal and this study aims to evaluate effects on infant immune development of formula feeding.

Methods And Study Design: A prospective study including 221 infants fed with breast milk or formula was conducted. At 3-month and 9-month, the concentrations of total immunoglobulin (Ig)G, IgM, IgA, IgG1, IgG2, interleukin (IL)-4, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) were measured by using enzyme-linked immunosorbent assay (ELISA). Natural killer (NK) cell activity and lymphocyte transformation testing were conducted. Furthermore, the occurrence of infantile diarrhea, respiratory infections and allergic diseases were questioned.

Results: The levels of total IgG (Z=-3.21, p=0.001), IgG1 (Z=-2.12, p=0.034), IFN-γ (t=-2.09, p=0.039) and NK cell activity (t=-2.14, p=0.034) were significant higher in formula-fed infants compared to breast-fed after 3 months. At 9-month, the levels of total IgG (Z=-4.34, p<0.001), IgA (Z=-2.05, p=0.041) and TNF-α (t=-2.10, p=0.037) of formula-fed infants were higher, but the lymphocyte stimulation index (t=2.76, p=0.007) was lower than breast-fed infants. While, no significant differences were found in the incidences of diarrhea and respiratory tract infection (p>0.05).

Conclusions: This investigation suggested that formula- and breast-feeding have different contributions to infant immune development, but the formula feeding would not cause significantly increase of diarrhea and respiratory infections.
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http://dx.doi.org/10.6133/apjcn.202103_30(1).0013DOI Listing
January 2021

PDIA6 contributes to aerobic glycolysis and cancer progression in oral squamous cell carcinoma.

World J Surg Oncol 2021 Mar 24;19(1):88. Epub 2021 Mar 24.

Department of Interventional Radiology, the Affiliated Cancer Hospital of Guizhou Medical University, Guiyang, 550002, People's Republic of China.

Background/objective: Accumulated evidence has demonstrated that aerobic glycolysis serves as a regulator of tumor cell growth, invasion, and angiogenesis. Herein, we explored the role of protein disulfide isomerase family 6 (PDIA6) in the aerobic glycolysis and the progression of oral squamous cell carcinoma (OSCC).

Methods: The expression pattern of PDIA6 in OSCC tissues was determined by qPCR and western blotting. Lentivirus and small interfering RNAs (siRNAs) were introduced into cells to upregulate and downregulate PDIA6 expression. CCK-8, flow cytometry, transwell, and xenotransplantation models were applied to detect cell proliferation, apoptosis, migration, invasion, and tumorigenesis, respectively.

Results: A high expression pattern of PDIA6 was observed in OSCC tissues, which was closely associated with lower overall survival and malignant clinical features in OSCC. Compared with the control group, overexpression of PDIA6 induced significant enhancements in cell growth, migration, invasiveness, and tumorigenesis and decreased cell apoptosis, while knockdown of PDIA6 caused opposite results. In addition, overexpression of PDIA6 increased glucose consumption, lactate production, and ATP level in OSCC cells.

Conclusion: This study demonstrated that PDIA6 expression was elevated in OSCC tissues, and overexpression of it promoted aerobic glycolysis and OSCC progression.
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http://dx.doi.org/10.1186/s12957-021-02190-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992853PMC
March 2021

Design, synthesis and bioactivity study on 5-phenylfuran derivatives as potent reversal agents against P-glycoprotein-mediated multidrug resistance in MCF-7/ADR cell.

Eur J Med Chem 2021 Apr 2;216:113336. Epub 2021 Mar 2.

College of Pharmaceutical Science & Green Pharmaceutical Collaborative Innovation Center of Yangtze River Delta Region, Zhejiang University of Technology, Hangzhou, 310014, China. Electronic address:

P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a phenomenon in which cells become resistant to structurally and mechanistically unrelated drugs resulting in low intracellular drug concentrations. It is one of the noteworthy problems in malignant tumor clinical therapeutics. So P-gp protein is one of the ideal targets to solve MDR. Based on the lead compound 5m obtained from our previous work, a series of furan derivatives featuring alkyl-substituted phenols and 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline were designed and synthesized as reversal agents against P-gp in this paper. Compound 16 containing isopropoxy possessed good potency against P-gp mediated MDR in MCF-7/ADR (IC (doxorubicin) = 0.73 μM, RF = 69.6 with 5 μM 16 treated). Western blot results and Rh123 accumulation assays showed that 16 effectively inhibited P-gp efflux function but not its expression. The preliminary structure-activity relationship and docking studies demonstrated that compound 16 would be a potential P-gp inhibitor. Most worthy of mention is that compound 16 has achieved satisfactory results in combination with a variety of anti-tumor drugs, such as doxorubicin, paclitaxel, and vincristine. This study forwards a hopeful P-gp inhibitor for withstanding malignant tumor cell with multidrug resistance setting the basis for further studies.
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http://dx.doi.org/10.1016/j.ejmech.2021.113336DOI Listing
April 2021

Emerging role of free triiodothyronine in patients with anti-N-methyl-D-aspartate receptor encephalitis.

Sci Rep 2021 Mar 15;11(1):6045. Epub 2021 Mar 15.

Department of Neurology, Zhengzhou University First Affiliated Hospital, Zhengzhou city, 450052, Henan Province, China.

We aimed to investigate the role of free triiodothyronine (FT3) in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. 137 consecutive inpatients (2016-2019) were registered prospectively and followed up for 12 months. 96 eligible patients were included in the study. The modified Rankin scale (mRS) score was collected, and the score of 3-6 was defined as a poor outcome. The patients were equally classified into 3 subgroups based on their FT3 levels obtained within 24 h of admission, and the subgroup differences were analyzed by parametric or nonparametric tests as appropriate. Logistic regression analysis was performed. We found that there was no difference in the mRS scores upon admission among 3 subgroups, however, patients in the low-FT3 subgroup tended to have higher disease severity during hospitalization and worse outcome in follow-up visits, represented by higher chances of intense care unit (ICU) admission (P < 0.001), longer hospital stay (P < 0.001), greater maximum mRS scores during hospitalization (P = 0.011), lower rates of getting clinical improvement within 4 weeks of starting treatment (P = 0.006), and higher percentages of poor 1-year outcome (P = 0.002). The level of FT3 was an independent factor correlated with ICU admission (P = 0.002) and might be a potential predictor for 1-year outcome. Our preliminary results suggest that the FT3 may be a risk factor involved in the evolution and progression of anti-NMDAR encephalitis, whereas the underline mechanisms remain to be explored. Attention should be paid to these patients with relatively low FT3 upon admission, which might possibly aid clinical prediction and guide clinical decision-making.
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http://dx.doi.org/10.1038/s41598-021-85596-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960963PMC
March 2021

Gradient Biomineralized Silk Fibroin Nanofibrous Scaffold with Osteochondral Inductivity for Integration of Tendon to Bone.

ACS Biomater Sci Eng 2021 03 10;7(3):841-851. Epub 2020 Jul 10.

Key Laboratory of Biorheological Science and Technology, Ministry of Education, Bioengineering College, Chongqing University, Chongqing 400044, P. R. China.

Enthesis injury repair remains a huge challenge because of the unique biomolecular composition, microstructure, and mechanics in the interfacial region. Surgical reconstruction often creates new bone-scaffold interfaces with mismatched properties, resulting in poor osseointegration. To mimic the natural interface tissue structures and properties, we fabricated a nanofibrous scaffold with gradient mineral coating based on 10 × simulated body fluid (SBF) and silk fibroin (SF). We then characterized the physicochemical properties of the scaffold and evaluated its biological functions both in vitro and in vivo. The results showed that different areas of SF nanofibrous scaffold had varying levels of mineralization with disparate mechanical properties and had different effects on bone marrow mesenchymal stem cell growth and differentiation. Furthermore, the gradient scaffolds exhibited an enhancement of integration in the tendon-to-bone interface with a higher ultimate load and more fibrocartilage-like tissue formation. These findings demonstrate that the silk-based nanofibrous scaffold with gradient mineral coating can regulate the formation of interfacial tissue and has the potential to be applied in interface tissue engineering.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01683DOI Listing
March 2021

TSUNAMI: Translational Bioinformatics Tool Suite for Network Analysis and Mining.

Genomics Proteomics Bioinformatics 2021 Mar 8. Epub 2021 Mar 8.

Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis IN 46202, USA. Electronic address:

Gene co-expression network (GCN) mining identifies gene modules with highly correlated expression profiles across samples/conditions. It enables researchers to discover latent gene/molecule interactions, identify novel gene functions, and extract molecular features from certain disease/condition groups, thus helping to identify disease biomarkers. However, there lacks an easy-to-use tool package for users to mine GCN modules that are relatively small in size with tightly connected genes that can be convenient for downstream gene set enrichment analysis, as well as modules that may share common members. To address this need, we developed an online GCN mining tool package: TSUNAMI (Tools SUite for Network Analysis and MIning). TSUNAMI incorporates our state-of-the-art lmQCM algorithm to mine GCN modules for both public and user-input data (microarray, RNA-seq, or any other numerical omics data), and then performs downstream gene set enrichment analysis for the identified modules. It has several features and advantages: 1) a user-friendly interface and real-time co-expression network mining through a web server; 2) direct access and search of NCBI GEO and TCGA databases, as well as user-input gene expression matrices for GCN module mining; 3) multiple co-expression analysis tools to choose from, all of which are highly flexible in regards to parameter selection options; 4) identified GCN modules are summarized to eigengenes, which are convenient for users to check their correlation with other clinical traits; 5) integrated downstream Enrichr enrichment analysis and links to other gene set enrichment tools; and 6) visualization of gene loci by Circos plot in any step of the process. The web service is freely accessible through URL: https://shiny.ph.iu.edu/TSUNAMI/. Source code is available at https://github.com/huangzhii/TSUNAMI/.
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http://dx.doi.org/10.1016/j.gpb.2019.05.006DOI Listing
March 2021

Paraspeckle Promotes Hepatocellular Carcinoma Immune Escape by Sequestering IFNGR1 mRNA.

Cell Mol Gastroenterol Hepatol 2021 Mar 2;12(2):465-487. Epub 2021 Mar 2.

School of Life Sciences, Westlake University, Hangzhou. Electronic address:

Background & Aims: Hepatocellular carcinoma (HCC) is the most common type of hepatic malignancies, with poor prognosis and low survival rate. Paraspeckles, which are unique subnuclear structures, are recently found to be involved in the development of various tumors, including HCC, and are related to induction in chemoresistance of HCC. This study aimed to investigate the possibility of paraspeckle in HCC cells participating in immune escape and its underlying mechanism in vitro and in vivo.

Methods: Expression of NEAT1_2, the framework of paraspeckle, in HCC cells and tissues was detected by qRT-PCR and RNA-FISH. mRNAs interacted with NEAT1_2 were pull-downed and sequenced in C-terminal S1-aptamer-tagged NEAT1_2 endogenously expressed HCC cells constructed using CRISPR-CAS9 knock-in technology. The effects of paraspeckle on HCC sensitivity to T-cell-mediated cytolysis were detected by T-cell mediated tumor cell killing assay. The roles of NEAT1_2 or NONO on IFNGR1 expression and IFN-γ signaling by applying gene function loss analysis in HCC cells were detected by qRT-PCR, RNA immunoprecipitation, Western blotting, and ELISA. The role of paraspeckle during adoptive T-cell transfer therapy for HCC in vivo was performed with a subcutaneous xenograft mouse.

Results: Paraspeckle in HCC cells is negatively related to T-cell-mediated cytolysis. Destruction of paraspeckle in HCC cells by knockdown of NEAT1_2 or NONO significantly improved the sensibility of resistant HCC cells to T-cell killing effects. Furthermore, IFNGR1 mRNA, which is sequestered by NEAT1_2 and NONO, is abundant in paraspeckle of T-cell killing-resistant HCC cells. Incapable IFN-γ-IFNGR1 signaling accounts for paraspeckle mediated-adoptive T-cell therapy resistance. Moreover, NEAT1_2 expression negatively correlates with IFNGR1 expression in clinical HCC tissues.

Conclusions: Paraspeckle in HCC cells helps tumor cells escape from immunosurveillance through sequestering IFNGR1 mRNA to inhibiting IFN-γ-IFNGR1 signaling, thereby avoiding T-cell killing effects. Collectively, our results hint that NEAT1_2 highly expressed HCC patient is more resistant to T-cell therapy in clinic, and NEAT1_2 may be potential target for HCC immunotherapy.
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http://dx.doi.org/10.1016/j.jcmgh.2021.02.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255817PMC
March 2021

Hypoperfusion assessed by pressure reactivity index is associated with delayed cerebral ischemia after subarachnoid hemorrhage: an observational study.

Chin Neurosurg J 2021 Mar 2;7(1):16. Epub 2021 Mar 2.

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

Background: Dysfunction of cerebral autoregulation is one of the pathophysiological mechanisms that causes delayed cerebral ischemia (DCI) after subarachnoid hemorrhage (SAH). Pressure reactivity index (PRx) have been confirmed to reflect the level of cerebral autoregulation and used to derive optimal cerebral perfusion pressure (CPPopt). The goal of this study is to explore the associations between autoregulation, CPPopt, PRx, and DCI.

Methods: Continuous intracranial pressure (ICP), arterial blood pressure (ABP), and cerebral perfusion pressure (CPP) signals acquired from 61 aSAH patients were retrospectively analyzed. PRx was calculated and collected by Pneumatic computer system. The CPP at the lowest PRx was determined as the CPPopt. The duration of a hypoperfusion event (dHP) was defined as the cumulative time that the PRx was > 0.3 and the CPP was
Results: Data from 52 patients were included in the final analysis of 61 patients. The mean %dHP in DCI was 29.23% and 10.66% in control. The mean %ΔCPPopt < - 10 mmHg was 22.28%, and 5.90% in control. The %dHP (p < 0.001) and the %ΔCPPopt < - 10mmHg (p < 0.001) was significantly longer in the DCI group. In multivariate logistic regression model, %ΔCPPopt <- 10 mmHg (p < 0.001) and %dHP (p < 0.001) were independent risk factor for predicting DCI, and %ΔCPPopt <- 10 mmHg (p = 0.010) and %dHP (p = 0.026) were independent risk factor for predicting unfavorable outcomes.

Conclusions: The increase of duration of hypoperfusion events and duration of CPP below CPPopt over 10 mmHg, evaluated as time of lowered CPP, is highly indicative of DCI and unfavorable outcomes.
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http://dx.doi.org/10.1186/s41016-021-00231-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923615PMC
March 2021

Orientation-independent reaction activity monitoring with single particle and data analytics.

J Colloid Interface Sci 2021 May 1;590:458-466. Epub 2021 Feb 1.

Key Laboratory of Luminescence Analysis and Molecular Sensing (Southwest University), Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, PR China.

Single-particle analysis is the most powerful method to obtain accurate local information for understanding and monitoring chemical reactions. However, investigations about obtaining comprehensive information at the single-particle level to overcome individual errors and sampling randomness have not been reported to date. Plasmonic nanorods, which have excellent anisotropic optical and chemical properties, make us in situ acquisition of conformation and dynamics of the biological information. On the basis of their anisotropic optical properties of the plasmonic nanorods such as Au nanorods (AuNRs) and data analytics, herein we developed a high-throughput resonance scattering imaging method of AuNRs under dark-field microscopy (DFM) to monitor orientation-independent reaction activity of AuNRs. Data analytics are introduced to determine a large number of AuNRs orientation obtained from a series of polarized DFM images, allowing us to real-time monitor reaction activity of AuNRs at all orientations, and also makes it possible to study the global and local reaction processes of AuNRs at single-particle level. Our method is expected to provide a new strategy for analytical study and single-particle sensing in chemistry.
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http://dx.doi.org/10.1016/j.jcis.2021.01.082DOI Listing
May 2021

Aligned Biofunctional Electrospun PLGA-LysoGM1 Scaffold for Traumatic Brain Injury Repair.

ACS Biomater Sci Eng 2020 04 4;6(4):2209-2218. Epub 2020 Mar 4.

School of Medicine, Chongqing University, Chongqing 400044, China.

Due to poor regenerative capabilities of the brain, a treatment for traumatic brain injury (TBI) presents a serious challenge to modern medicine. Biofunctional scaffolds that can support neuronal growth, guide neurite elongation, and re-establish impaired brain tissues are urgently needed. To this end, we developed an aligned biofunctional scaffold (aPLGA-LysoGM1), in which poly (lactic--glycolic acid) (PLGA) was functionalized with sphingolipid ceramide -deacylase (SCDase)-hydrolyzed monosialotetrahexosylganglioside (LysoGM1) and electrospinning was used to form an aligned fibrous network. As a ganglioside of neuronal membranes, the functionalized LysoGM1 endows the scaffold with unique biological properties favoring the growth of neuron and regeneration of injured brain tissues. Moreover, we found that the aligned PLGA-LysoGM1 fibers acted as a topographical cue to guide neurite extension, which is critical for organizing the formation of synaptic networks (neural networks). Systematic in vitro studies demonstrated that the aligned biofunctional scaffold promotes neuronal viability, neurite outgrowth, and synapse formation and also protects neurons from pressure-related injury. Additionally, in a rat TBI model, we demonstrated that the implantation of aPLGA-LysoGM1 scaffold supported recovery from brain injury, as more endogenous neurons were found to migrate and infiltrate into the defect zone compared with alternative scaffold. These results suggest that the aligned biofunctional aPLGA-LysoGM1 scaffold represents a promising therapeutic strategy for brain tissue regeneration following TBI.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01636DOI Listing
April 2020

Low expression of miR-142-3p promotes intervertebral disk degeneration.

J Orthop Surg Res 2021 Jan 14;16(1):55. Epub 2021 Jan 14.

Department of Thoracolumbar Spine Surgery, The Second Affiliated Hospital of Inner Mongolia Medical University, No. 1 Yingfang Road, Hohhot City, 010059, Inner Mongolia, China.

Background: Intervertebral disk degeneration (IDD) is a degenerative disease characterized by cytoplasm loss and extracellular matrix degradation. Numerous evidence reported that miRNAs participated in IDD development. Nevertheless, the function of miR-142-3p in IDD development remains unknown. This study mainly explored the potential role and function of miR-142-3p in IDD development.

Methods: One percent fetal bovine serum was used to induce the degeneration of ATDC5 cells, and miR-142-3p level was examined by qRT-PCR. Then, miR-142-3p mimic/inhibitor and its corresponding negative control were transfected into ATDC5 normal and degenerative cells. Viability, migration, invasion, apoptosis, cycle, Bax, Bcl-2, P62, and Beclin1 expression levels were assessed using CCK8, wound healing assay, annexin V-FITC/PI staining, western blot, and qRT-PCR, respectively.

Results: The results revealed that the expression levels of MMP13, ADAMTS5, MMP3, and Col-X were increased as well as the expression levels of SOX-9 and Col-II were reduced in ATDC5 degenerative cells, indicating the degeneration model was constructed. We observed that miR-142-3p was decreased in ATDC5 degenerative cells and its suppression could promote ATDC5 cell degeneration. However, miR-142-3p overexpression could reverse the cell viability inhibition, as well as apoptosis and autophagy enhancement in ATDC5 degenerative cells.

Conclusions: Our results proved that miR-142-3p may play an important role in disk degeneration. Further animal study is needed to illustrate the role of the miR-142-3p in IDD development.
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http://dx.doi.org/10.1186/s13018-020-02194-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809750PMC
January 2021

Combinatorial analyses reveal cellular composition changes have different impacts on transcriptomic changes of cell type specific genes in Alzheimer's Disease.

Sci Rep 2021 01 11;11(1):353. Epub 2021 Jan 11.

Department of Medical and Molecular Genetics, Indiana University, School of Medicine, Indianapolis, IN, 46202, USA.

Alzheimer's disease (AD) brains are characterized by progressive neuron loss and gliosis. Previous studies of gene expression using bulk tissue samples often fail to consider changes in cell-type composition when comparing AD versus control, which can lead to differences in expression levels that are not due to transcriptional regulation. We mined five large transcriptomic AD datasets for conserved gene co-expression module, then analyzed differential expression and differential co-expression within the modules between AD samples and controls. We performed cell-type deconvolution analysis to determine whether the observed differential expression was due to changes in cell-type proportions in the samples or to transcriptional regulation. Our findings were validated using four additional datasets. We discovered that the increased expression of microglia modules in the AD samples can be explained by increased microglia proportions in the AD samples. In contrast, decreased expression and perturbed co-expression within neuron modules in the AD samples was likely due in part to altered regulation of neuronal pathways. Several transcription factors that are differentially expressed in AD might account for such altered gene regulation. Similarly, changes in gene expression and co-expression within astrocyte modules could be attributed to combined effects of astrogliosis and astrocyte gene activation. Gene expression in the astrocyte modules was also strongly correlated with clinicopathological biomarkers. Through this work, we demonstrated that combinatorial analysis can delineate the origins of transcriptomic changes in bulk tissue data and shed light on key genes and pathways involved in AD.
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http://dx.doi.org/10.1038/s41598-020-79740-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801680PMC
January 2021

ISO/IEEE 11073 Treadmill Interoperability Framework and its Test Method: Design and Implementation.

JMIR Med Inform 2020 Dec 9;8(12):e22000. Epub 2020 Dec 9.

Bioengineering College, Chongqing University, Chongqing, China.

Background: Regular physical activity is proven to help prevent and treat noncommunicable diseases such as heart disease, stroke, diabetes, and breast and colon cancer. The exercise data generated by health and fitness devices (eg, treadmill, exercise bike) are very important for health management service providers to develop personalized training programs. However, at present, there is little research on a unified interoperability framework in the health and fitness domain, and there are not many solutions; besides, the privatized treadmill data transmission scheme is not conducive to data integration and analysis.

Objective: This article will expand the IEEE 11073-PHD standard protocol family, develop standards for health and fitness device (using treadmill as an example) based on the latest version of the 11073-20601 optimized exchange protocol, and design protocol standards compliance testing process and inspection software, which can automatically detect whether the instantiated object of the treadmill meets the standard.

Methods: The study includes the following steps: (1) Map the data transmitted by the treadmill to the 11073-PHD objects; (2) Construct a programming language structure corresponding to the 11073-PHD application protocol data unit (APDU) to complete the coding and decoding part of the test software; and (3) Transmit the instantiated simulated treadmill data to the gateway test software through transmission control protocol for standard compliance testing.

Results: According to the characteristics of the treadmill, a data exchange framework conforming to 11073-PHD is constructed, and a corresponding testing framework is developed; a treadmill agent simulation is implemented, and the interoperability test is performed. Through the designed testing process, the corresponding testing software was developed to complete the standard compliance testing of the treadmill.

Conclusions: The extended research of IEEE 11073-PHD in the field of health and fitness provides a potential new idea for the data transmission framework of sports equipment such as treadmills, which may also provide some help for the development of sports health equipment interoperability standards.
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http://dx.doi.org/10.2196/22000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758169PMC
December 2020

Phenolic and Volatile Compounds in the Production of Sugarcane Vinegar.

ACS Omega 2020 Dec 17;5(47):30587-30595. Epub 2020 Nov 17.

Key Laboratory of Sugarcane Biotechnology and Genetic Improvement (Guangxi), Ministry of Agriculture and Rural Affairs/ Guangxi Key Laboratory of Sugarcane Genetic Improvement/ Sugarcane Research Institute, Guangxi Academy of Agricultural Sciences, Nanning 530 007, Guangxi, China.

This study aimed to explore the dynamic variations in the phenolic and volatile organic compounds of sugarcane vinegar subjected to different production processes. The determination of phenolic and volatile organic compounds was performed by UPLC-MS and solid phase micro extraction (SPME) coupled with gas chromatography combined with mass spectrometry (GC-MS). The complete fermentation process of sugarcane lasted nine days, and production of vinegar of up to 3.04% (w/v), total acids, and 4.1° alcoholicity was accomplished. Various phenolic compounds of sugarcane juice (non-sterilized) and those of alcoholic and acetic acid fermentation were obtained after nine days of fermentation. These were benzoic acid (2.024, 1.002, and 1.027 mg L), ferulic acid (0.060, 0.205, and 1.124 mg L), quinic acid (0.019, 0.074, and 0.031 mg L), chlorogenic acid (0.349, 1.635, and 1.217 mg L), apigenin (0.002, 0.099, and 0.004 mg L), kaempferol (0.003, 0.336, and 0.003 mg L), caffeic acid (-, 0.005, and 0.005 mg L), luteolin (0.003, 0.323, and 0.005 mg L), and -coumaric acid (0.018, 0.015, and 0.027 mg L). Forty-five volatile organic compounds were also identified. The sugarcane juice can be commercialized as an alternative to wine as it presents characteristics of an alcoholic fermented beverage.
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http://dx.doi.org/10.1021/acsomega.0c04524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714267PMC
December 2020

Repetitive transcranial magnetic stimulation (rTMS) fails to improve cognition in patients with parkinson's disease: a Meta-analysis of randomized controlled trials.

Int J Neurosci 2020 Nov 18:1-14. Epub 2020 Nov 18.

Department of Neurology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Neuroscience Institute, Guangzhou, China.

Background: Cognitive decline is one of the greatest concerns for patients with Parkinson's disease (PD) and their care partners. Repetitive transcranial magnetic stimulation (rTMS) is a nonpharmacological treatment option used to improve cognitive function in PD, but its efficacy is unclear. We performed a meta-analysis to determine whether rTMS improves cognition in PD patients.

Methods: Eligibility criteria (PICOS) were as follows: (1) 'P': The patients participating were diagnosed with idiopathic PD; (2) 'I': Intervention using rTMS; (3) 'C': Sham stimulation as control; (4) 'O': The outcome of the study included cognitive evaluations; (5) 'S': The study adopted randomized controlled design. The standardized mean difference (SMD) of change of score was applied to measure efficacy, and we used Version 2 of the Cochrane tool to assess risk of bias.

Results: Twelve studies met the inclusion criteria. Compared with sham-controlled group, the pooled result showed a non-significant short-term effect of rTMS on global cognition (SMD: -0.15, 95% CI: -0.59 to 0.29, = 36.7%), executive function (SMD: 0.03, 95% CI: -0.21 to 0.26, = 0.0%), and attention and working memory (SMD: 0.05, 95% CI: -0.25 to 0.35, = 0.0%). Long-term outcomes were either shown to be statistically nonsignificant.

Conclusions: Based on a limited number of studies, rTMS fails to improve cognition in PD. We call for additional high-quality randomized controlled trials with adequate sample sizes to determine the efficacy of rTMS.
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http://dx.doi.org/10.1080/00207454.2020.1809394DOI Listing
November 2020

Discovery of 12O-A Novel Oral Multi-Kinase Inhibitor for the Treatment of Solid Tumor.

Molecules 2020 Nov 9;25(21). Epub 2020 Nov 9.

Department of Medicinal Chemistry, School of Medicine, Nankai University, 94 Weijin Road, Tianjin 300071, China.

A novel series of pyrimidine-benzotriazole derivatives have been synthesized and evaluated for their anticancer activity against human solid tumor cell lines. The most promising molecule was identified for its excellent antiproliferative activities, especially against the SiHa cell line with IC value as 0.009 μM. Kinase inhibition assay assessed was a potential multi-kinase inhibitor, which possessed potent inhibitory activities against cyclin-dependent kinases (CDKs) and fms-like tyrosine kinase (FLT) with IC values in the nanomolar range. Molecular docking studies illustrated that the introduction of triazole moiety in was critical for CDKs inhibition. In addition, inhibited cancer cell proliferation, colony-formation, and cell cycle progression and provoked apoptotic death in vitro. In an SiHa xenograft mouse model, a once-daily dose of compound at 20 mg/kg significantly suppressed the tumor growth without obvious toxicity. Taken together, provided valuable guide for further structural optimization for CDKs and FLT inhibitors.
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http://dx.doi.org/10.3390/molecules25215199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664879PMC
November 2020
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