Publications by authors named "Jing Liang"

660 Publications

Analytical Cryo-Scanning Electron Microscopy of Hydrated Polymers and Microgels.

Acc Chem Res 2021 May 4. Epub 2021 May 4.

Stevens Institute of Technology Hoboken, New Jersey 07030, United States.

ConspectusDespite the fact that scanning electron microscopes (SEM) coupled with energy-dispersive X-ray microanalysis (EDS) has been commercially available for more than a half-century, SEM/EDS continues to develop and open new opportunities to study the morphology of advanced materials. This is particularly true in applications to hydrated soft matter. Developments in field-emission electron sources that enable low-voltage imaging of uncoated polymers, silicon-drift detectors that enable high-efficiency collection of X-rays characteristic of light elements, and cryogenic methods to effectively cryo-fix hydrated samples have opened new opportunities to apply techniques relatively well established in hard-materials applications to challenging new problems involving synthetic polymers. We have applied cryo-SEM imaging and spatially resolved EDS to collect new information characterizing polyelectrolyte microgels. These are charged gel particles with dimensions in the range of 0.1-100 μm. Perhaps most notable is the fact that the high hydration levels-the samples are mostly water-allow robust calibration curves to be generated using frozen-hydrated buffers with known salt and/or hydrocarbon compositions. Such calibration curves enable quantitative composition measurements in the low-concentration extremes associated with high-swelling hydrogels. We use an experimentally derived carbon calibration curve to determine the microgel swell ratio, . The swell ratio, arguably, is the single most important gel characteristic because it is directly related to the mesh size of the networked polymer, which in turn determines many of the gel's mechanical and transport properties. While can be experimentally measured in macroscopic gels based on weight measurements in the dry and hydrated states, it is very difficult to measure in a microgel, and the fact that EDS in a cryo-SEM can determine from a single X-ray spectrum is significant. Furthermore, because of the electrostatic charge distributed along the polymer chains, the presence and concentration of counter-ions play a critical role in polyelectrolyte systems. While conceptually understood for decades, experimental measurements of counter-ion concentrations have been largely limited to a relatively small set of materials that involve macroscopic samples. By developing calibration curves from frozen-hydrated buffer of known ionic strength, we measure the concentration of Na counter-ions in microgels of poly(acrylic acid) (PAA) with a limit of detection of ∼0.014 M. Such measurements may help resolve some long-standing questions in polyelectrolyte science concerning counter-ion condensation. Even in the absence of a calibration curve, we show that spatially resolved X-ray spectroscopy can map the spatial distribution of a cationic oligopeptide complexed within a hydrated PAA microgel because of the nitrogen fingerprint that, albeit at very low concentration, is unique to the peptide. We look specifically at the case of a microgel with a so-called core-shell structure, where, again, the underlying polyelectrolyte science responsible for core-shell formation remains incompletely understood. These examples highlight how a modern cryo-SEM can be exploited to quantitatively characterize hydrated soft matter. The approach is almost certain to continue its development and impact as the base of experienced practitioners, the accessibility to well-configured microscopes, and the abundance of challenging problems involving hydrated soft matter all continue to grow.
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http://dx.doi.org/10.1021/acs.accounts.1c00109DOI Listing
May 2021

Receptor-mediated mitophagy regulates EPO production and protects against renal anemia.

Elife 2021 May 4;10. Epub 2021 May 4.

Chinese Academy of Medical Sciences, Institute of Hematology and Blood Diseases Hospital, Tianjin, China.

Erythropoietin (EPO) drives erythropoiesis and is secreted mainly by the kidney upon hypoxic or anemic stress. The paucity of EPO production in renal EPO-producing cells (REPs) causes renal anemia, one of the most common complications of chronic nephropathies. Although mitochondrial dysfunction is commonly observed in several renal and hematopoietic disorders, the mechanism by which mitochondrial quality control impacts renal anemia remains elusive. In this study, we showed that FUNDC1, a mitophagy receptor, plays a critical role in EPO-driven erythropoiesis induced by stresses. Mechanistically, EPO production is impaired in REPs in mice upon stresses, and the impairment is caused by the accumulation of damaged mitochondria, which consequently leads to the elevation of the reactive oxygen species (ROS) level and triggers inflammatory responses by up-regulating proinflammatory cytokines. These inflammatory factors promote the myofibroblastic transformation of REPs, resulting in the reduction of EPO production. We therefore provide a link between aberrant mitophagy and deficient EPO generation in renal anemia. Our results also suggest that the mitochondrial quality control safeguards REPs under stresses, which may serve as a potential therapeutic strategy for the treatment of renal anemia.
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http://dx.doi.org/10.7554/eLife.64480DOI Listing
May 2021

A stepwise processing strategy for treating highly acidic wastewater and comprehensive utilization of the products derived from different treating steps.

Chemosphere 2021 Apr 26;280:130646. Epub 2021 Apr 26.

School of Chemistry and Chemical Engineering, Guangxi University, Nanning, 530004, China.

A stepwise processing strategy, including initial neutralization, chemical mineralization, and complete neutralization treating steps, was developed to effectively treat and utilize the highly acidic wastewater derived from titanium dioxide production. Approximately 94.6% of SO, 100% of Fe, and most of other metals were recovered to produce white gypsum, schwertmannite, and Fe/FeO@biochar (Fe/FeO@BC) composite in the corresponding treating steps. The resulting effluent with neutral pH and a small amount of metal ions could be discharged to general sewage treatment plant for further processing. Schwertmannite was applied as a heterogeneous Fenton-like catalyst to stimulate HO to produce active radicals for effective degradation and mineralization of methyl orange (MO) in solution. The MO removal of 100% and total organic carbon removal of 91.1% were achieved in schwertmannite/HO reaction system, and schwertmannite exhibited good stability and reusability. Fe/FeO@BC composite was applied to remove Cr(VI), with the adsorption capacity of 67.74 mg g. The removal of Cr(VI) using Fe/FeO@BC composite was a chemisorption process, including the adsorption of Cr(VI), reduction of Cr(VI) to Cr(III), and co-precipitation of Cr(III)/Fe(III) oxides/hydroxides. This stepwise treating strategy is a promising technology for effective treatment of highly acidic industrial wastewater and comprehensive utilization of the related products.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130646DOI Listing
April 2021

Specimen number based diagnostic yields of suspicious axillary lymph nodes in core biopsy in breast cancer: clinical implications from a prospective exploratory study.

Quant Imaging Med Surg 2021 May;11(5):2151-2161

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background: Ultrasound (US)-guided core needle biopsy (CNB) is widely applied in the pathological diagnosis of suspicious axillary lymph nodes (ALNs) in breast cancer. However, the number of specimens removed during biopsy is currently based on the preference of the individual radiologist. This study aims to analyze the specimen number based diagnostic yields of US guided CNB of suspicious ALNs in breast cancer.

Methods: Core biopsy specimens of suspicious lymph nodes were prospectively obtained from breast cancer patients treated at our hospital between November, 2018, and July, 2019. Four specimens were obtained from each patient and labeled 1-4 in the order they were removed. Each specimen underwent pathological evaluation to determine whether metastasis had occurred. The diagnostic yields of the specimens were calculated and differences in diagnostic accuracy according to the number of specimens were evaluated by McNemar's test.

Results: A total of 167 patients were enrolled, and 139 (83.2%) cases were identified as metastasis by CNB. The diagnostic yields were: 74.2% (specimen 1), 87.8% (specimens 1-2), 91.2% (specimens 1-3), and 94.6% (specimens 1-4). The increases in diagnostic yield from specimen 1 to 1-2 and from specimens 1-2 to 1-4 were significant; however, no significant differences were detected between specimens 1-3 and the first two, or between specimens 1-4 and the first three in this sample size. The lower diagnostic abilities for the first two specimens were associated with shorter long- and short-axis lengths of lymph nodes on US.

Conclusions: Although the second specimen contributed significant diagnostic yield of suspicious axillary lymph nodes in core biopsy in breast cancer, a minimum number cannot be determined by this study. Additional specimens may improve diagnostic yield particularly in patients with small nodes.
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http://dx.doi.org/10.21037/qims-20-1030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047355PMC
May 2021

Research trends and hotspots of health-related quality of life: a bibliometric analysis from 2000 to 2019.

Health Qual Life Outcomes 2021 Apr 23;19(1):130. Epub 2021 Apr 23.

School of Health Sciences, Wuhan University, NO. 115 Donghu Road, Wuhan City, 430071, China.

Background: The number of research articles on health-related quality of life (HRQoL) has been strikingly increasing. This study aimed to explore the general trends and hotspots of HRQoL.

Methods: Based on the Web of Science database, research on HRQoL published between 2000 and 2019 were identified. A bibliometric analysis was performed based on the number of articles, citations, published journals, authors' addresses, and keywords. Descriptive analysis, visualization of geographic distribution and keyword clustering analysis were applied to the collected data.

Results: The annual number of articles showed growth over the past twenty years, but the annual total citations and annual citations per article were both in decreasing trends. Articles about HRQoL were more likely to be published in journals of multi-subject categories. The HRQoL research was mainly distributed across North America and Europe throughout the twenty years and ushered in a vigorous development worldwide after 2015. Cooperation strength between domestic institutions was much greater than that of international institutions. HRQoL research had six concentrated clusters: HRQoL, Depression, Obesity, Disability, Oncology, Fatigue.

Conclusion: This study provided an overall perspective of global research trends and hotspots in HRQoL, and a potential insight for future research. HRQoL research had experienced significant increasing development during 2000-2019, especially the HRQoL measurement instruments, however, there were significant regional disparities in scientific output in HRQoL.
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http://dx.doi.org/10.1186/s12955-021-01767-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063463PMC
April 2021

How does health literacy affect the utilization of basic public health services in Chinese migrants?

Health Promot Int 2021 Apr 11. Epub 2021 Apr 11.

Department of Social Medicine and Health Management, School of Health Sciences, Wuhan University, No.115 Donghu Road, Wuhan City 430071, China.

Previous studies have focused on the determinants of basic public health services utilization, such as socioeconomic status and mobility characteristics, rather than on health literacy. Thus, this study aimed to estimate the effect of health literacy on the utilization of basic public health services among Chinese migrants. Based on the 2016 China Migrants Dynamic Survey data (N = 2335), this study used propensity score matching approach to estimate the effect of health literacy on the utilization of basic public health services, including the establishment of health records and receipt of health education, and to explore heterogeneity in this effect based on educational attainment and urban-rural status. The findings show that high levels of health literacy increased the probability of establishing health records and receiving more health education. Also, high levels of health literacy had a positive effect on the utilization of basic public health services among Chinese migrants, especially those with less education or living in urban areas. Policy makers should more carefully consider the actual situation and needs of migrants who are living in urban areas or have less education, constructing more targeted service programs.
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http://dx.doi.org/10.1093/heapro/daab040DOI Listing
April 2021

Combination of Mesenchymal Stem Cell and Endothelial Progenitor Cell Infusion Accelerates Injured Intestinal Repair by Regulating Gut Microbiota after Hematopoietic Cell Transplantation.

Transplant Cell Ther 2021 Feb 13;27(2):152.e1-152.e9. Epub 2020 Dec 13.

Institute of Blood Diseases, Xuzhou Medical University, Xuzhou, Jiangsu, China; Department of Hematology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Key Laboratory of Bone Marrow Stem Cells, Xuzhou Medical University, Xuzhou, Jiangsu, China; School of Medical Technology, Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address:

Mesenchymal stem cells (MSC) have been widely applied for repairing intestinal barrier function and restoring immune homeostasis for pretransplantation conditioning, yet the repair process is often impaired or delayed owing to a lack of vascularity. How combined therapy with MSC and endothelial progenitor cells (EPC) for the intestinal microenvironment and repair remain unclear. In this study, BALB/c mice received syngeneic bone marrow transplantation with or without MSC or EPC infusion. The findings show that the MSC+EPC mice had greater blood capillary distribution and higher expression of tight junction protein (occludin) in the small intestinal tract. Meanwhile, the MSC+EPC cotreatment increased IL-17A levels and decreased IFN-γ levels at the early stage after transplantation. Furthermore, the MSC+EPC treatment motivated p38 mitogen-activated protein kinase (MAPK) and enhanced heat shock protein 27 (HSP27) activation, which subsequently promoted intestinal epithelial cell proliferation and down-regulated apoptosis-related molecule caspase 3 expression. Finally, the high-throughput sequencing of gut microbiota (16S) showed that the MSC+EPC treatment can inhibit the Enterococcus population (<0.5%) and stabilize the Akkermansia population (~15%), with the Akkermansia population showing significant positive correlations with p38 MAPK/phos-p38, HSP27/phos-HSP27, IL-17A, and occludin. Taken together, our results show that MSC+EPC combined therapy is beneficial for the repair of injured intestine and drives gut microbial community stability by regulating the intestinal microenvironment.
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http://dx.doi.org/10.1016/j.jtct.2020.10.013DOI Listing
February 2021

A Novel Dual Drug Approach That Combines Ivermectin and Dihydromyricetin (DHM) to Reduce Alcohol Drinking and Preference in Mice.

Molecules 2021 Mar 22;26(6). Epub 2021 Mar 22.

Titus Family Department of Clinical Pharmacy, University of Southern California School of Pharmacy, Los Angeles, CA 90089, USA.

Alcohol use disorder (AUD) affects over 18 million people in the US. Unfortunately, pharmacotherapies available for AUD have limited clinical success and are under prescribed. Previously, we established that avermectin compounds (ivermectin [IVM] and moxidectin) reduce alcohol (ethanol/EtOH) consumption in mice, but these effects are limited by P-glycoprotein (Pgp/ABCB1) efflux. The current study tested the hypothesis that dihydromyricetin (DHM), a natural product suggested to inhibit Pgp, will enhance IVM potency as measured by changes in EtOH consumption. Using a within-subjects study design and two-bottle choice study, we tested the combination of DHM (10 mg/kg; i.p.) and IVM (0.5-2.5 mg/kg; i.p.) on EtOH intake and preference in male and female C57BL/6J mice. We also conducted molecular modeling studies of DHM with the nucleotide-binding domain of human Pgp that identified key binding residues associated with Pgp inhibition. We found that DHM increased the potency of IVM in reducing EtOH consumption, resulting in significant effects at the 1.0 mg/kg dose. This combination supports our hypothesis that inhibiting Pgp improves the potency of IVM in reducing EtOH consumption. Collectively, we demonstrate the feasibility of this novel combinatorial approach in reducing EtOH consumption and illustrate the utility of DHM in a novel combinatorial approach.
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http://dx.doi.org/10.3390/molecules26061791DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004700PMC
March 2021

Slow Walking in Individuals with Chronic Post-Stroke Hemiparesis: Speed Mediated Effects of Gait Kinetics and Ankle Kinematics.

Brain Sci 2021 Mar 13;11(3). Epub 2021 Mar 13.

Department of Physical Therapy, University of Nevada, Las Vegas, NV 89154, USA.

Post-stroke rehabilitation often aims to increase walking speeds, as faster walking is associated with improved functional status and quality of life. However, for successful community ambulation, ability to modulate (increase and decrease) walking speeds is more important than walking continuously at constant speeds. Increasing paretic propulsive forces to increase walking speed has been extensively examined; however, little is known about the mechanics of slow walking post-stroke. The primary purpose of this study was to identify the effects of increased and decreased walking speeds on post-stroke kinetics and ankle kinematics. Fifteen individuals with chronic post-stroke hemiparesis and 15 non-neurologically impaired controls walked over an instrumented treadmill under: slow, self-selected, and fast walking speeds. We examined the peak propulsive forces, propulsive impulse, peak braking forces, braking impulse, and ankle kinematics under each condition. When walking at slow walking speeds, paretic limbs were unable to reduce braking impulse and peak propulsive force or modulate ankle kinematics. Impaired modulation of paretic gait kinetics during slow walking places people post-stroke at high risks for slip-related falls. These findings suggest the need for developing gait retraining paradigms for slow walking in individuals chronically post-stroke that target the ability of the paretic limb to modulate braking forces.
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http://dx.doi.org/10.3390/brainsci11030365DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000078PMC
March 2021

Ferrocene-Based Metal-Organic Framework Nanosheets as a Robust Oxygen Evolution Catalyst.

Angew Chem Int Ed Engl 2021 Mar 26. Epub 2021 Mar 26.

State Key Laboratory of Fine Chemicals, Dalian University of Technology, 116024, Dalian, P. R. China.

We report the synthesis of two-dimensional metal-organic frameworks (MOFs) on nickel foam (NF) by assembling nickel chloride hexahydrate and 1,1'-ferrocenedicarboxylic acid (NiFc-MOF/NF). The NiFc-MOF/NF exhibits superior oxygen evolution reaction (OER) performance with an overpotential of 195 mV and 241 mV at 10 and 100 mA cm , respectively under alkaline conditions. Electrochemical results demonstrate that the superb OER performance originates from the ferrocene units that serve as efficient electron transfer intermediates. Density functional theory calculations reveal that the ferrocene units within the MOF crystalline structure enhance the overall electron transfer capacity, thereby leading to a theoretical overpotential of 0.52 eV, which is lower than that (0.81 eV) of the state-of-the-art NiFe double hydroxides.
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http://dx.doi.org/10.1002/anie.202101878DOI Listing
March 2021

Effects of Clostridium butyricum on growth performance, metabonomics and intestinal microbial differences of weaned piglets.

BMC Microbiol 2021 Mar 22;21(1):85. Epub 2021 Mar 22.

College of Animal Science and Technology, Shihezi University, Shihezi, Xinjiang, 832003, People's Republic of China.

Background: Weaning stress of piglets causes a huge economic loss to the pig industry. Balance and stability of the intestinal microenvironment is an effective way to reduce the occurance of stress during the weaning process. Clostridium butyricum, as a new microecological preparation, is resistant to high temperature, acid, bile salts and some antibiotics. The aim of present study is to investigate the effects of C. butyricum on the intestinal microbiota and their metabolites in weaned piglets.

Results: There was no statistical significance in the growth performance and the incidence of diarrhoea among the weaned piglets treated with C. butyricum during 0-21 days experimental period. Analysis of 16S rRNA gene sequencing results showed that the operational taxonomic units (OTUs), abundance-based coverage estimator (ACE) and Chao index of the CB group were found to be significantly increased compared with the NC group (P < 0.05). Bacteroidetes, Firmicutes and Tenericutes were the predominant bacterial phyla in the weaned piglets. A marked increase in the relative abundance of Megasphaera, Ruminococcaceae_NK4A214_group and Prevotellaceae_UCG-003, along with a decreased relative abundance of Ruminococcaceae_UCG-005 was observed in the CB group, when compared with the NC group (P < 0.05). With the addition of C. butyricum, a total of twenty-two significantly altered metabolites were obtained in the feces of piglets. The integrated pathway analysis by MetaboAnalyst indicated that arginine and proline metabolism; valine, leucine and isoleucine biosynthesis; and phenylalanine metabolism were the main three altered pathways, based on the topology. Furthermore, Spearman's analysis revealed some altered gut microbiota genus such as Oscillospira, Ruminococcaceae_NK4A214_group, Megasphaera, Ruminococcaceae_UCG-005, Prevotella_2, Ruminococcaceae_UCG-002, Rikenellaceae_RC9_gut_group and Prevotellaceae_UCG-003 were associated with the alterations in the fecal metabolites (P < 0.05), indicating that C. butyricum presented a potential protective impact through gut microbiota. The intestinal metabolites changed by C. butyricum mainly involved the variation of citrulline, dicarboxylic acids, branched-chain amino acid and tryptophan metabolic pathways.

Conclusions: Overall, this study strengthens the idea that the dietary C. butyricum treatment can significantly alter the intestinal microbiota and metabolite profiles of the weaned piglets, and C. butyricum can offer potential benefits for the gut health.
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http://dx.doi.org/10.1186/s12866-021-02143-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7983215PMC
March 2021

The effect of pressure variation on droplet size distribution of dispersed oil under simulated deep-water conditions.

Heliyon 2021 Mar 11;7(3):e06291. Epub 2021 Mar 11.

Northern Region Persistent Organic Pollution Control (NRPOP) Laboratory, Faculty of Engineering and Applied Science, Memorial University of Newfoundland, St. John's, NL A1B 3X5, Canada.

Droplet size distribution of dispersed oil in deep-water is critical to the transport and biodegradation of spilled oil in deep-sea. Few studies have focused on the effects of pressure on chemically dispersed oil through experiments. This study thus simulated how the crude oil homogenously pre-dispersed by Corexit 9500A using baffled flasks would behave after being exposed to deep-water conditions. Key factors included dispersant-to-oil ratio (DOR), mixing energy (energy dissipation rate and Kolmogorov microscale), and pressure (up to 150 bar). The variations of pressure were demonstrated to have insignificant effects on the size distribution of pre-dispersed oil. Both the average and medium droplet sizes were correlated negatively with DOR and mixing energy in an established model with a p-value ≤ 0.0011. The log-normal and log-logistic distributions provided a reasonable fit to simulate the droplet size distribution. The two parameters of log-logistic distribution were dependent on DOR and mixing energy with a p-value < 0.005. The results would be valuable to advance the understanding of the behaviours and trajectories of chemically dispersed oil under deep-water conditions. The research helped provide more scientific evidence to improve the understanding of dispersed oil behaviours under high pressure and support deep-sea oil spill research and potential extension of the existing results from shallow water to deep water conditions.
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http://dx.doi.org/10.1016/j.heliyon.2021.e06291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966848PMC
March 2021

Pretreatment method for hypochlorite decon water before GC analysis of HD, VX, and GD.

Water Sci Technol 2021 Mar;83(5):985-992

Institute of Chemical Defense, Beijing, China E-mail:

Active chlorine decontaminants like hypochlorite are used to destroy chemical warfare agents (CWAs) such as HD, VX and GD due to the former's strong oxidation capacity and high nucleophilicity. In this paper, experiments were performed to identify the main factors affecting agent recovery from decon water. Based on the results, a method to recover residual CWAs from hypochlorite decon water before quantitative determination by GC was developed. The results showed that the extraction solvent was a critical determinant of high CWA recovery. Dichloromethane was more suitable than petroleum either, especially for samples containing GD or low residual CWAs. For VX-containing samples, the use of an alkali solution improved VX recovery. Neutralization was also important for a high CWA recovery, especially for samples with low CWA concentrations and/or strong decontaminant reactivity. The use of 15% sodium sulfite as the neutralization solution gave the best results for hypochlorite decon water. When the optimized conditions of simultaneous sodium sulfite neutralization and dichloromethane extraction were used, the recovery of HD, VX and GD in hypochlorite decon water was greater than 85% at a concentration range of 20 mg/L to 10,000 mg/L.
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http://dx.doi.org/10.2166/wst.2021.034DOI Listing
March 2021

Effects of augmented somatosensory input using vibratory insoles to improve walking in individuals with chronic post-stroke hemiparesis.

Gait Posture 2021 May 23;86:77-82. Epub 2021 Jan 23.

Department of Industrial Engineering and Engineering Management, National Tsing-Hua University, Hsinchu, Taiwan.

Background: Stroke survivors suffer from hemiparesis and somatosensory impairments, which adversely impact walking performance, placing them at higher risks for trips and falls. Post-stroke, somatosensory deficits are commonly observed as impaired interpretation of afferent input and increased threshold. Diminishing or augmenting somatosensory inputs via various techniques have been demonstrated to be able to modify static and dynamic balance, postural and locomotor control in non-neurologically impaired as well as neurologically impaired individuals.

Research Question: We sought to investigate whether enhancing somatosensory input using vibratory insoles, can improve post-stroke gait. We hypothesized that with augmentation of somatosensory input at the soles via vibratory insoles would improve post-stroke gait via increased propulsive forces, decreased braking forces and increased ankle angle movements in the paretic legs of individuals with chronic post-stroke hemiparesis.

Methods: Fifteen individuals with chronic post-stroke hemiparesis and 15 age-similar non-neurologically impaired controls participated in this cross-sectional study. Enhanced somatosensory stimulation was delivered using a pair of tactor-embedded insoles, providing suprathreshold vibratory stimulation to the bottom of the feet. Participants walked over an instrumented treadmill with self-selected speeds, under 5 conditions: no insole in shoe (NT), insoles in shoe with no vibration (BOFF), vibration under both feet (BON), vibration under one foot only (ION, CON). Kinetics and kinematics during walking were recorded and analyzed offline.

Results: Suprathreshold vibratory stimulations did not alter gait kinetics under any stimulation conditions. We observed increased paretic ankle dorsiflexions in the paretic legs, when vibratory stimuli were applied unilaterally.

Significance: Vibratory stimulations applied at suprathreshold intensity to the bottom of the feet to augment somatosensory feedback can potentially be used as a low-cost solution to address the inadequate toe clearance during walking in people post-stroke, which is an important goal in post-stroke rehabilitation.
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http://dx.doi.org/10.1016/j.gaitpost.2021.01.016DOI Listing
May 2021

TRPS1 drives heterochromatic origin refiring and cancer genome evolution.

Cell Rep 2021 Mar;34(10):108814

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Health Science Center, Beijing 100191, China; Department of Biochemistry and Molecular Biology, School of Medicine, Hangzhou Normal University, Hangzhou 311121, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China. Electronic address:

Exploitation of naturally occurring genetic mutations could empower the discovery of novel aspects of established cancer genes. We report here that TRPS1, a gene linked to the tricho-rhino-phalangeal syndrome (TRPS) and recently identified as a potential breast cancer driver, promotes breast carcinogenesis through regulating replication. Epigenomic decomposition of TRPS1 landscape reveals nearly half of H3K9me3-marked heterochromatic origins are occupied by TRPS1, where it encourages the chromatin loading of APC/C, resulting in uncontrolled origin refiring. TRPS1 binds to the genome through its atypical H3K9me3 reading via GATA and IKAROS domains, while TRPS-related mutations affect its chromatin binding, replication boosting, and tumorigenicity. Concordantly, overexpression of wild-type but not TRPS-associated mutants of TRPS1 is sufficient to drive cancer genome amplifications, which experience an extrachromosomal route and dynamically evolve to confer therapeutic resistance. Together, these results uncover a critical function of TRPS1 in driving heterochromatin origin firing and breast cancer genome evolution.
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http://dx.doi.org/10.1016/j.celrep.2021.108814DOI Listing
March 2021

Antituberculosis Drugs (Rifampicin and Isoniazid) Induce Liver Injury by Regulating NLRP3 Inflammasomes.

Mediators Inflamm 2021 19;2021:8086253. Epub 2021 Feb 19.

Nanchong Key Laboratory of Individualized Drug Therapy, Nanchong, Sichuan, China.

Patients being treated for pulmonary tuberculosis often suffer liver injury due to the effects of anti-TB drugs, and the underlying mechanisms for those injuries need to be clarified. In this study, rats and hepatic cells were administrated isoniazid (INH) and rifampin (RIF) and then treated with NLRP3-inflammasome inhibitors (INF39 and CP-456773) or NLRP3 siRNA. Histopathological changes that occurred in liver tissue were examined by H&E staining. Additionally, the levels IL-33, IL-18, IL-1, NLRP3, ASC, and cleaved-caspase 1 expression in the liver tissues were also determined. NAT2 and CYP2E1 expression were identified by QRT-PCR analysis. Finally, assays were performed to examine the effects of siRNA targeting NLRP3. Treatment with the antituberculosis drugs caused significant liver injuries, induced inflammatory responses and oxidative stress (OS), activated NLRP3 inflammasomes, reduced the activity of drug-metabolizing enzymes, and altered the antioxidant defense system in rats and hepatic cells. The NLRP3 inflammasome was required for INH- and RIF-induced liver injuries that were produced by inflammatory responses, OS, the antioxidant defense system, and drug-metabolizing enzymes. This study indicated that the NLRP3 inflammasome is involved in antituberculosis drug-induced liver injuries (ATLIs) and suggests NLRP3 as a potential target for attenuating the inflammation response in ATLIs.
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http://dx.doi.org/10.1155/2021/8086253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914095PMC
February 2021

The HIF-1α antisense long non-coding RNA drives a positive feedback loop of HIF-1α mediated transactivation and glycolysis.

Nat Commun 2021 02 26;12(1):1341. Epub 2021 Feb 26.

Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.

Hypoxia-inducible factor-1 (HIF-1) is a master driver of glucose metabolism in cancer cells. Here, we demonstrate that a HIF-1α anti-sense lncRNA, HIFAL, is essential for maintaining and enhancing HIF-1α-mediated transactivation and glycolysis. Mechanistically, HIFAL recruits prolyl hydroxylase 3 (PHD3) to pyruvate kinase 2 (PKM2) to induce its prolyl hydroxylation and introduces the PKM2/PHD3 complex into the nucleus via binding with heterogeneous nuclear ribonucleoprotein F (hnRNPF) to enhance HIF-1α transactivation. Reciprocally, HIF-1α induces HIFAL transcription, which forms a positive feed-forward loop to maintain the transactivation activity of HIF-1α. Clinically, high HIFAL expression is associated with aggressive breast cancer phenotype and poor patient outcome. Furthermore, HIFAL overexpression promotes tumor growth in vivo, while targeting both HIFAL and HIF-1α significantly reduces their effect on cancer growth. Overall, our results indicate a critical regulatory role of HIFAL in HIF-1α-driven transactivation and glycolysis, identifying HIFAL as a therapeutic target for cancer treatment.
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http://dx.doi.org/10.1038/s41467-021-21535-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7910558PMC
February 2021

Design of an Extreme Low Cutoff Frequency Highpass Frontend for CMOS ISFET via Direct Tunneling Principle.

IEEE Trans Biomed Circuits Syst 2021 Feb 26;PP. Epub 2021 Feb 26.

In this work, ISFET frontends utilising the direct tunneling current to eliminate trapped charge are proposed. The principle has been investigated and verified via silicon-imitated ISFET first, where silicon capacitors are used to imitate the passivation ones. Because the dominant tunneling components depend on the potential difference between Gate and Drain terminals, a source-follower structure could itself perform a highpass filter with time constant at 10-100 seconds level. Additionally, a time-constant regulation mechanism is presented by feeding the output signal back to the drain terminal of ISFETs, achieving a regulation factor over 50, namely from 4.7 seconds to 243.4 seconds in our implementation. Afterwards in chemical test, proposed ISFETs have been verified in terms of unit passivation capacitance, linearity, noise and sensitivity for ISFETs with 3 different top metal areas. It is found that approximately 30 mV/pH sensitivity can be achieved, and for the first time we managed to derive the relation between chemical flicker noise and sensing metal area.
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http://dx.doi.org/10.1109/TBCAS.2021.3062445DOI Listing
February 2021

The effects of myeloablative or non-myeloablative total body irradiations on intestinal tract in mice.

Biosci Rep 2021 Mar;41(3)

Institute of Blood Diseases, Xuzhou Medical University, Xuzhou, Jiangsu 221002, China.

Acute radiation injury caused by high-dose radiation exposure severely impedes the application of radiotherapy in cancer management. To deeply understand the side effects of radiation on intestinal tract, an irradiation murine model was applied and evaluated. C57BL/6 mice were given 4 Gy non-myeloablative irradiation, 8 Gy myeloablative irradiation and non-irradiation (control), respectively. Results demonstrated that the 8 Gy myeloablative irradiations significantly damaged the gut barrier along with decreasing MECA32 and ZO-1. However, a slight increase in MECA32 and ZO-1 was detected in the 4 Gy non-myeloablative irradiations treatment from day 5 to day 10. Further, the irradiations affected the expression of P38 and JNK mitogen-activated protein kinase (MAPK) but not ERK1/2 MAPK signal pathway. Moreover, irradiation had adverse effects on hematopoietic system, altered the numbers and percentages of intestinal inflammatory cells. The IL-17/AhR had big increase in the gut of 4 Gy irradiation mice at day 10 compared with other groups. Both 8 Gy myeloablative and 4 Gy non-myeloablative irradiation disturbed the levels of short-chain fatty acids (SCFAs) in intestine. Meanwhile, high dosage of irradiation decreased the intestinal bacterial diversity and altered the community composition. Importantly, the fatty acids generating bacteria Bacteroidaceae and Ruminococcaceae played key roles in community distribution and SCFAs metabolism after irradiation. Collectively, the irradiation induced gut barrier damage with dosages dependent that led to the decreased p38 MAPK and increased JNK MAPK, unbalanced the mononuclear cells (MNCs) of gut, disturbed intestinal bacterial community and SCFAs level.
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http://dx.doi.org/10.1042/BSR20202993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926181PMC
March 2021

Triptolide Attenuates Vascular Calcification by Upregulating Expression of miRNA-204.

Front Pharmacol 2020 11;11:581230. Epub 2021 Jan 11.

Drug Research and Development Center, School of Pharmacy, Third-Grade Pharmacology Laboratory of State, Administration of Traditional Chinese Medicine, Anhui Provincial Engineering Research Center for Polysaccharide Drugs, Wannan Medical College, Wuhu, China.

Triptolide (TP), a naturally derived compound from , has been proven effective in protecting against cardiovascular system, but the molecular mechanisms underlying its protective effects are poorly understood. In the current study, we sought to test the potential protective role of TP in the regulation of vascular calcification in a rat model and explore whether TP attenuates medial vascular calcification by upregulating miRNA-204. Vitamin D3 plus nicotine (VDN) was used to induce a vascular calcification (VC) model of rat aorta. Von Kossa and Hematoxylin-Eosin staining were applied to assess the degree of calcification of rat aortas. Calcium content and alkaline phosphatase activity were measured. Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was applied to quantify miRNA-204 expression. The localization of runt-related transcription factor-2 (RUNX2) and bone morphogenetic protein-2 (BMP2) expressions were detected by immunohistochemistry and western blotting. Administration of TP greatly reduced vascular calcification in a dose-dependent manner compared with VC controls. The increase in ALP activity and calcium content was ameliorated by TP. Moreover, protein expression levels of BMP2 and RUNX2 were significantly reduced in calcified aortas. MiRNA-204 expression was increased in the TP-treated groups compared with VC controls and the effects of TP were reversed by the intravenous injection of miRNA-204-interfering lentivirus. However, the miRNA-204-overexpressing lentivirus had no additional effects on ALP activity, calcium content, BMP2 and RUNX2 expressions compared with those from TP group. TP inhibited BMP2 and RUNX2 expression and attenuated vascular calcification via upregulating the level of miRNA-204. TP appears to be a potential new therapeutic option for treating vascular calcification.
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http://dx.doi.org/10.3389/fphar.2020.581230DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883594PMC
January 2021

Immune abscopal effect of microwave ablation for lung metastases of endometrial carcinoma.

J Cancer Res Ther 2020 ;16(7):1718-1721

Department of Oncology, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Lung Cancer Institute, Weihai, Shandong, China.

Increasing evidence support that microwave ablation (MWA) induces spontaneous abscopal regression of the tumor, also called as the abscopal effect. Although the abscopal effect after MWA is a rare event, several studies have suggested that this effect is the result of the activation of the immune system induced by the death of immunogenic tumor cells. Here, we have presented the case of a 65-year-old woman with primary endometrial cancer who developed bilateral pulmonary metastases. After local MWA of one lesion in her right lung, progressive regression of the other lesions in the right and left lungs was recorded. This case supports the hypothesis that the abscopal effect is attributable to the activation of the systemic immune response.
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http://dx.doi.org/10.4103/jcrt.JCRT_1399_20DOI Listing
January 2020

Primary Squamous Cell Carcinoma of the Liver is Rare but Hostile: Case Series and Comprehensive Review of the Literature.

Cancer Manag Res 2021 29;13:829-837. Epub 2021 Jan 29.

Department of Oncology, The First Affiliated Hospital of Shandong First Medical University, Jinan, People's Republic of China.

Primary squamous cell carcinoma (SCC) of the liver is an uncommon cancer type. Only dozens of such cases have been reported in the literature. We reviewed three cases with primary SCC of the liver in a single center from January 2013 to October 2019. One case was positive for hepatitis B infection and simultaneously diagnosed with sigmoid adenocarcinoma and liver cyst. The second patient presented with hepatolithiasis. The remaining one had no history of prior liver insult, hepatic infection or any pre-existing hepatic cysts. Two cases had a long survival of more than one year through chemotherapy, or radical surgery plus transarterial chemoembolization. We also found 25 patients with primary hepatic SCC in the Surveillance, Epidemiology and End Results (SEER) database from 1997 to 2016. The median age was 67 years (range 33-87 years). The median overall survival and disease-specific survival were 7.7 months (range 0.0-76.0 months) and 2.0 months (range 0.0-20.0 months), respectively. Furthermore, patients receiving surgery had a longer median OS (20.0 versus 6.0 months, = 0.016) and DSS (48.0 versus 8.0 months, = 0.03) than those receiving palliative treatment. Only 20% of all cases survived for more than a year. Although primary SCC of the liver has an unfavorable prognosis, radical surgery and systematic treatment might be helpful for clinical management.
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http://dx.doi.org/10.2147/CMAR.S290523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7853432PMC
January 2021

Comorbidities and factors influencing frequent gout attacks in patients with gout: a cross-sectional study.

Clin Rheumatol 2021 Feb 4. Epub 2021 Feb 4.

Department of Rheumatology and Immunology, Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, 510630, China.

Objectives: The objective was to identify the comorbidities of gout, to compare gender difference and independent factors of frequent gout attacks (> 20 times).

Method: Demographic, clinical variables, self-reported comorbidities, and biochemical variables (i.e., initial serum uric acid (UA) and UA at visit) were collected in this cross-sectional study. Gout attack times were recorded as ≤ 5, 6-10, 11-20, and > 20. Adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated to explore the association between selected risk factors and frequent gout attacks.

Results: Six hundred fifty-three gout patients with a mean age of 48.3 ± 15.8 years were included, 84.7% of whom were males. The median gout duration was 6.0 (3.0-12.0) years. The most common comorbidities involved hypertension (166, 25.4%), coronary artery disease (CAD) (67, 10.3%), chronic kidney disease (66, 10.1%), and hyperlipidemia (57, 8.7%). Abnormalities including nephrolithiasis (29.4%), hydronephrosis (3.2%), and gallstones (11.9%) were also found. Although female patients had a longer disease duration and more CAD, they had a lower level of UA, creatine, and C-reactive protein (CRP) but higher high-density lipoprotein cholesterol (HDL-C) (p < 0.05). A positive correlation between UA and triglycerides was found in females (p = 0.039). Patients with renal insufficiency or nephrolithiasis had longer disease duration and more gout attacks (p < 0.001). In multivariable regression analysis, only gout duration (OR = 7.89, p < 0.001) and UA (OR = 1.48, p < 0.001) was independent factors of frequent gout attacks.

Conclusions: Comorbidity screening involving dyslipidemia is often neglected in gout patients. Gout duration and UA are the risk factors of frequent gout attacks. Key Points • Comorbidities can be overlooked if the screening for lipid levels, cardiovascular disease, and kidney disease is not completed. • There are differences in comorbidities and biochemical findings between male and female patients with gout. • Gout duration and serum uric acid level are independent risk factors of frequent gout attacks.
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http://dx.doi.org/10.1007/s10067-021-05595-wDOI Listing
February 2021

Comprehensive landscape and future perspectives of circular RNAs in colorectal cancer.

Mol Cancer 2021 02 3;20(1):26. Epub 2021 Feb 3.

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

Colorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research.
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http://dx.doi.org/10.1186/s12943-021-01318-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856739PMC
February 2021

The miR-1185-2-3p-GOLPH3L pathway promotes glucose metabolism in breast cancer by stabilizing p53-induced SERPINE1.

J Exp Clin Cancer Res 2021 Jan 28;40(1):47. Epub 2021 Jan 28.

Taishan People's Hospital, Postdoctoral Innovation Practice Base of Southern Medical University, Taishan, 529200, China.

Background: Phosphatidylinositol-4-phosphate-binding protein GOLPH3L is overexpressed in human ductal carcinoma of the breast, and its expression levels correlate with the prognosis of breast cancer patients. However, the roles of GOLPH3L in breast tumorigenesis remain unclear.

Methods: We assessed the expression and biological function of GOLPH3L in breast cancer by combining bioinformatic prediction, metabolomics analysis and RNA-seq to determine the GOLPH3L-related pathways involved in tumorigenesis. Dual-luciferase reporter assay and coimmunoprecipitation (Co-IP) were used to explore the expression regulation mechanism of GOLPH3L.

Results: We demonstrated that knockdown of GOLPH3L in human breast cancer cells significantly suppressed their proliferation, survival, and migration and suppressed tumor growth in vivo, while overexpression of GOLPH3L promoted aggressive tumorigenic activities. We found that miRNA-1185-2-3p, the expression of which is decreased in human breast cancers and is inversely correlated with the prognosis of breast cancer patients, is directly involved in suppressing the expression of GOLPH3L. Metabolomics microarray analysis and transcriptome sequencing analysis revealed that GOLPH3L promotes central carbon metabolism in breast cancer by stabilizing the p53 suppressor SERPINE1.

Conclusions: In summary, we discovered a miRNA-GOLPH3L-SERPINE1 pathway that plays important roles in the metabolism of breast cancer and provides new therapeutic targets for human breast cancer.
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http://dx.doi.org/10.1186/s13046-020-01767-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842049PMC
January 2021

Changes of Metabolites in Acute Ischemic Stroke and Its Subtypes.

Front Neurosci 2020 11;14:580929. Epub 2021 Jan 11.

Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Existing techniques have many limitations in the diagnosis and classification of ischemic stroke (IS). Considering this, we used metabolomics to screen for potential biomarkers of IS and its subtypes and to explore the underlying related pathophysiological mechanisms. Serum samples from 99 patients with acute ischemic stroke (AIS) [the AIS subtypes included 49 patients with large artery atherosclerosis (LAA) and 50 patients with small artery occlusion (SAO)] and 50 matched healthy controls (HCs) were analyzed by non-targeted metabolomics based on liquid chromatography-mass spectrometry. A multivariate statistical analysis was performed to identify potential biomarkers. There were 18 significantly different metabolites, such as oleic acid, linoleic acid, arachidonic acid, L-glutamine, L-arginine, and L-proline, between patients with AIS and HCs. These different metabolites are closely related to many metabolic pathways, such as fatty acid metabolism and amino acid metabolism. There were also differences in metabolic profiling between the LAA and SAO groups. There were eight different metabolites, including L-pipecolic acid, 1-Methylhistidine, PE, LysoPE, and LysoPC, which affected glycerophospholipid metabolism, glycosylphosphatidylinositol-anchor biosynthesis, histidine metabolism, and lysine degradation. Our study effectively identified the metabolic profiles of IS and its subtypes. The different metabolites between LAA and SAO may be potential biomarkers in the context of clinical diagnosis. These results highlight the potential of metabolomics to reveal new pathways for IS subtypes and provide a new avenue to explore the pathophysiological mechanisms underlying IS and its subtypes.
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http://dx.doi.org/10.3389/fnins.2020.580929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829509PMC
January 2021

Clinical characteristics, rates of blindness, and geographic features of PACD in China.

Can J Ophthalmol 2021 Jan 21. Epub 2021 Jan 21.

The Eye Hospital of Wenzhou Medical University, Wenzhou, China.

Objective: To analyze the rates of blindness with the demographics and clinical characteristics of patients with primary angle-closure disease (PACD) to provide a comprehensive epidemiologic reference in China.

Methods: A retrospective analysis was conducted in the Chinese Glaucoma Study Consortium database, which is a national multicenter glaucoma research alliance of 111 hospitals participating between December 21, 2015 and September 9, 2018. The diagnosis of PACD was made by qualified physicians through examination. Comparison of sex, age, family history, subtypes of PACD, and blindness were analyzed.

Results: A total of 5762 glaucoma patients were included, of which 4588 (79.6%) had PACD. Of PACD patients, 72.1% were female with the sex ratio (F/M) of 2.6, and the average age of patients was 63.8±9.3 years with the majority between 60 and 70 years. Additionally, 30% of these patients had low vision in one eye, 8.8% had low vision in both eyes, 1.7% had blindness in one eye, and 0.3% had blindness in both eyes. There were statistical differences with regards to age between male and female patients with PACD, with male patients being older on average. Primary angle-closure glaucoma was more commonly diagnosed in males (60%) compared to females (35.9%), whereas acute primary angle closure (APAC) was more commonly diagnosed in females (54.3%) compared to males (37.7%). The visual acuity in APAC patients was lower and the rate of low vision and blindness was higher than other subtypes.

Conclusion: PACD was the major type of glaucoma in Chinese hospitals. There were more female patients with PACD, mostly between 60 and 70 years old, with higher rates of APAC in women. APAC resulted in the worst visual outcomes of all PACD subtypes.
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http://dx.doi.org/10.1016/j.jcjo.2020.12.010DOI Listing
January 2021

Engineering of stepwise-targeting chitosan oligosaccharide conjugate for the treatment of acute kidney injury.

Carbohydr Polym 2021 Mar 31;256:117556. Epub 2020 Dec 31.

Institute of Drug Discovery Technology, Ningbo University, Ningbo, 315211, Zhejiang, China. Electronic address:

Acute kidney injury (AKI) is a common and serious clinical syndrome of acute renal dysfunction in a short period. One of therapeutic interventions for AKI is to reduce ROS massively generated in the mitochondria and then ameliorate cell damage and apoptosis induced by oxidative stress. In this study, stepwise-targeting chitosan oligosaccharide, triphenyl phosphine-low molecular weight chitosan-curcumin (TPP-LMWC-CUR, TLC), was constructed for sepsis-induced AKI via removing excessive ROS in renal tubular epithelial cells. Benefiting from good water solubility and low molecular weight, TLC was rapidly and preferentially distributed in the renal tissues and then specifically internalized by tubular epithelium cells via interaction between Megalin receptor and LMWC. The intracellular TLC could further delivery CUR to mitochondria due to high buffering capacity of LMWC and delocalized positive charges of TPP. Both in vitro and in vivo pharmacodynamic results demonstrated the enhanced therapeutic effect of TLC in the treatment of AKI.
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http://dx.doi.org/10.1016/j.carbpol.2020.117556DOI Listing
March 2021

Glutamine's protection against brain damage in septic rats via increased protein oxygen-N-acetylglucosamine modification.

Neuroreport 2021 02;32(3):214-222

Department of Anesthesiology, Zhongda Hospital, Southeast University, Nanjing, China.

Objective: This study aimed to observe the effect of glutamine (Gln) on brain damage in septic rats and explore its possible mechanism.

Methods: Ninety-three Sprague-Dawley rats were randomly divided into five groups: sham operation group, sepsis group, Gln-treated group, quercetin/Gln-treated group, and alloxan/Gln-treated group. The rats in each group were continuously monitored for mean arterial pressure (MAP) and heart rate changes for 16 h. Neuroreflex scores were measured 24 h after surgery. The water content of the brain tissue was measured. Plasma neuron enolase and cysteine protease-3 were measured using the ELISA. The expression levels of heat shock protein 70 (HSP70) and oxygen-N-acetylglucosamine (O-GlcNAc) were determined by western blot analysis. Finally, the brain tissue was observed via hematoxylin and eosin staining.

Results: The brain tissue water content, plasma neuron enolase content, brain tissue cysteine protease-3 content, and nerve reflex score were significantly lower in the Gln-treated group than in the sepsis group (P < 0.05). At the same time, the pathological brain tissue damage in the Gln-treated group was also significantly reduced. It is worth noting that the expression of HSP70 and the protein O-GlcNAc modification levels in the Gln-treated group were significantly elevated than the levels in the sepsis group (P < 0.05), and reversed by pretreatment with the HSP and O-GlcNAc inhibitors quercetion and alloxan.

Conclusions: Gln can attenuate brain damage in rats with sepsis, which may be associated with increased protein O-GlcNAc modification.
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http://dx.doi.org/10.1097/WNR.0000000000001582DOI Listing
February 2021

Network controllability-based algorithm to target personalized driver genes for discovering combinatorial drugs of individual patients.

Nucleic Acids Res 2021 04;49(7):e37

Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy Science, Shanghai 200031, China.

Multiple driver genes in individual patient samples may cause resistance to individual drugs in precision medicine. However, current computational methods have not studied how to fill the gap between personalized driver gene identification and combinatorial drug discovery for individual patients. Here, we developed a novel structural network controllability-based personalized driver genes and combinatorial drug identification algorithm (CPGD), aiming to identify combinatorial drugs for an individual patient by targeting personalized driver genes from network controllability perspective. On two benchmark disease datasets (i.e. breast cancer and lung cancer datasets), performance of CPGD is superior to that of other state-of-the-art driver gene-focus methods in terms of discovery rate among prior-known clinical efficacious combinatorial drugs. Especially on breast cancer dataset, CPGD evaluated synergistic effect of pairwise drug combinations by measuring synergistic effect of their corresponding personalized driver gene modules, which are affected by a given targeting personalized driver gene set of drugs. The results showed that CPGD performs better than existing synergistic combinatorial strategies in identifying clinical efficacious paired combinatorial drugs. Furthermore, CPGD enhanced cancer subtyping by computationally providing personalized side effect signatures for individual patients. In addition, CPGD identified 90 drug combinations candidates from SARS-COV2 dataset as potential drug repurposing candidates for recently spreading COVID-19.
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http://dx.doi.org/10.1093/nar/gkaa1272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053130PMC
April 2021