Publications by authors named "Kang Xia"

115 Publications

MiR-6924-5p-rich exosomes derived from genetically modified Scleraxis-overexpressing PDGFRα(+) BMMSCs as novel nanotherapeutics for treating osteolysis during tendon-bone healing and improving healing strength.

Biomaterials 2021 Nov 5;279:121242. Epub 2021 Nov 5.

Department of Orthopedics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, First Affiliated Hospital of Third Military Medical University (Army Medical University), Chongqing, 400000, China. Electronic address:

Osteolysis at the tendon-bone interface can impair pullout strength during tendon-bone healing and lead to surgery failure, but the effects of clinical treatments are not satisfactory. Mesenchymal stem cell (MSC)-derived exosomes have been used as potent and feasible natural nanocarriers for drug delivery and have been proven to enhance tendon-bone healing strength, indicating that MSC-derived exosomes could be a promising therapeutic strategy. In this study, we explored Scleraxis (Scx) dynamically expressed in PDGFRα(+) bone marrow-derived mesenchymal stem cells (BMMSCs) during natural tendon-bone healing. Then, we investigated the role of PDGFRα(+) BMMSCs in tendon-bone healing after Scx overexpression as well as the underlying mechanisms. Our data demonstrated that Scx-overexpressing PDGFRα(+) BMMSCs (BMMSC) could efficiently inhibit peritunnel osteolysis and enhance tendon-bone healing strength by preventing osteoclastogenesis in an exosomes-dependent manner. Exosomal RNA-seq revealed that the abundance of a novel miRNA, miR-6924-5p, was highest among miRNAs. miR-6924-5p could directly inhibit osteoclast formation by binding to the 3'-untranslated regions (3'UTRs) of OCSTAMP and CXCL12. Inhibition of miR-6924-5p expression reversed the prevention of osteoclastogenic differentiation by BMMSC derived exosomes (BMMSC-exos). Local injection of BMMSC-exos or miR-6924-5p dramatically reduced osteoclast formation and improved tendon-bone healing strength. Furthermore, delivery of miR-6924-5p efficiently inhibited the osteoclastogenesis of human monocytes. In brief, our study demonstrates that BMMSC-exos or miR-6924-5p could serve as a potential therapy for the treatment of osteolysis during tendon-bone healing and improve the outcome.
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http://dx.doi.org/10.1016/j.biomaterials.2021.121242DOI Listing
November 2021

Immunosenescence evaluation of peripheral blood lymphocyte subsets in 957 healthy adults from 20 to 95 years old.

Exp Gerontol 2021 Oct 30;157:111615. Epub 2021 Oct 30.

Department of Laboratory Medicine, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China. Electronic address:

Immunosenescence is characterized by an age-related decline in immune system function. Major efforts have been made to identify changes in peripheral blood lymphocyte subsets accompanying immunosenescence in elderly adults. However, the change trends of some lymphocyte subsets with age are still controversial, and populations of advanced ages, such as people in their 80s or 90s, have not yet been thoroughly investigated. To provide further insight, we recruited 957 healthy donors without certain diseases with ages ranging from 20 to 95 years. Peripheral lymphocyte subsets, including T cells, CD4 T cells, CD8 T cells, B cells and NK cells, and the CD4/CD8 ratio were measured by flow cytometry. Additionally, regulatory CD4 T cells with inhibitory functions marked by CD3CD4CD25 and the expression of the costimulatory molecule CD28 on CD8 T cells were evaluated. Sex was considered at the same time. The data indicated that in elderly people, peripheral T (p < 0.001), CD4 T (p < 0.001) and B (p < 0.001) lymphocyte subsets decreased, but the NK cell population (p < 0.001) increased. More regulatory CD4 T cells may imply stronger inhibition in the elderly population. The decreased CD28 expression with age in females verified CD28 to be an immunosenescence marker and the sharply decreased CD28 expression after 75 years in males indicated a rapid immunosenescence at the late life span of the male populations. In addition, our study established reference values for peripheral lymphocyte subsets at different age stages in males and females, which are urgently needed for the clinical management and treatment of geriatric diseases.
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http://dx.doi.org/10.1016/j.exger.2021.111615DOI Listing
October 2021

Author Correction: Development of a valid Chinese version of the Cumberland Ankle Instability Tool in Chinese-speaking patients with chronic ankle instability disorders.

Sci Rep 2021 Sep 7;11(1):18149. Epub 2021 Sep 7.

Department of Orthopedics, The General Hospital of Western Theater Command, Tianhui Road 270, Chengdu City, 610000, People's Republic of China.

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http://dx.doi.org/10.1038/s41598-021-97504-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423763PMC
September 2021

Validation and Prediction of the School Psychological Capital Among Chinese College Students.

Front Psychol 2021 9;12:697703. Epub 2021 Jul 9.

School of Foreign Languages and Literature, Yunnan Normal University, Kunming, China.

This study validated the school psychological capital (PsyCap) scale in the Chinese context and examined the predictive effect of PsyCap resources on academic engagement and achievement emotions. Self-report data for PsyCap resources, student engagement, enjoyment, anxiety, and boredom toward English learning were collected from 1,000 sophomores. Item-level analyses and confirmatory factor analysis were used to verify the validity of the school PsyCap scale, and structural equation modeling was applied to reveal the predictive effect of school PsyCap resources on academic engagement and achievement emotions. Results showed that the school PsyCap scale retained superior psychometric properties. Besides, PsyCap resources were demonstrated to have a positive relationship to academic engagement and enjoyment, and a negative relationship to anxiety and boredom. The effectiveness of the school PsyCap scale was verified among Chinese college students, and besides the traditional predictors, school PsyCap is also critically important for students' academic engagement and achievement emotions. Limitations and implications are discussed.
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http://dx.doi.org/10.3389/fpsyg.2021.697703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8299118PMC
July 2021

The Effects of Sevoflurane vs. Propofol for Inflammatory Responses in Patients Undergoing Lung Resection: A Meta-Analysis of Randomized Controlled Trials.

Front Surg 2021 2;8:692734. Epub 2021 Jul 2.

Department of Anesthesiology and Perioperative Medicine, Henan University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China.

Inflammatory cytokines are increased during one-lung ventilation in patients undergoing lung resection, and this increase can be fatal. Propofol and sevoflurane are the main anesthetics used for these patients. Unfortunately, there is no consensus on the best choice of an anesthetic agent concerning an inflammatory response in patients undergoing lung resection. This meta-analysis aimed to compare the effects of propofol and sevoflurane on the inflammatory response in patients undergoing lung resection. We searched electronic databases to identify randomized controlled trials comparing the effects of different anesthetics (sevoflurane vs. propofol) on the inflammatory response. The primary outcome concerned the concentration of systemic inflammatory cytokines. The secondary outcomes concerned the concentrations of inflammatory cytokines in the bronchoalveolar lavage (BAL) fluid from the dependent and independent lung. Random effects analysis of the meta-analyses were performed to synthesize the evidence and to assess the concentrations of inflammatory factors in the sevoflurane and propofol groups. Eight trials involving 488 participants undergoing lung resection with one-lung ventilation were included. There was no significant difference in the concentrations of systemic interleukin (IL)-6, IL-10, or tumor necrosis factor α between the sevoflurane and propofol groups. Compared with the propofol group, BAL levels of IL-6 in the dependent ventilated lung were decreased in the sevoflurane group (three trials, 256 participants; standardized mean difference [SMD], -0.51; 95% confidence interval [CI], -0.90 to -0.11; = 0.01; = 46%). The BAL levels of IL-6 in the independent ventilated lung were also decreased by sevoflurane (four trials, 362 participants; SMD, -0.70; 95% [CI], -0.93 to -0.47; < 0.00001; = 0%). There was no difference in the systemic inflammatory response between the sevoflurane and propofol groups. However, compared with propofol, sevoflurane can reduce the local alveolar inflammatory response. Additional research is necessary to confirm whether the inflammatory response is direct or indirect.
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http://dx.doi.org/10.3389/fsurg.2021.692734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282814PMC
July 2021

Individualized positive end-expiratory pressure (PEEP) during one-lung ventilation for prevention of postoperative pulmonary complications in patients undergoing thoracic surgery: A meta-analysis.

Medicine (Baltimore) 2021 Jul;100(28):e26638

Department of Anesthesia and Perioperative Medicine, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, Henan, China.

Background: Positive end-expiratory pressure (PEEP) is an important part of the lung protection strategies for one-lung ventilation (OLV). However, a fixed PEEP value is not suitable for all patients. Our objective was to determine the prevention of individualized PEEP on postoperative complications in patients undergoing one-lung ventilation.

Method: We searched the PubMed, Embase, and Cochrane and performed a meta-analysis to compare the effect of individual PEEP vs fixed PEEP during single lung ventilation on postoperative pulmonary complications. Our primary outcome was the occurrence of postoperative pulmonary complications during follow-up. Secondary outcomes included the partial pressure of arterial oxygen and oxygenation index during one-lung ventilation.

Result: Eight studies examining 849 patients were included in this review. The rate of postoperative pulmonary complications was reduced in the individualized PEEP group with a risk ratio of 0.52 (95% CI:0.37-0.73; P = .0001). The partial pressure of arterial oxygen during the OLV in the individualized PEEP group was higher with a mean difference 34.20 mm Hg (95% CI: 8.92-59.48; P = .0004). Similarly, the individualized PEEP group had a higher oxygenation index, MD: 49.07mmHg, (95% CI: 27.21-70.92; P < .0001).

Conclusions: Individualized PEEP setting during one-lung ventilation in patients undergoing thoracic surgery was associated with fewer postoperative pulmonary complications and better perioperative oxygenation.
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http://dx.doi.org/10.1097/MD.0000000000026638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284741PMC
July 2021

Plasma therapy cured a COVID-19 patient with long duration of viral shedding for 49 days: The clinical features, laboratory tests, plasma therapy, and implications for public health management.

MedComm (2020) 2020 May 27. Epub 2020 May 27.

Department of Biochemistry and Molecular Biology Third Military Medical University (Army Medical University) Chongqing People's Republic of China.

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http://dx.doi.org/10.1002/mco2.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7262084PMC
May 2020

Development of a valid Chinese version of the Cumberland Ankle Instability Tool in Chinese-speaking patients with chronic ankle instability disorders.

Sci Rep 2021 05 7;11(1):9747. Epub 2021 May 7.

Department of Orthopedics, The General Hospital of Western Theater Command, Tianhui Road 270, Chengdu City, 610000, People's Republic of China.

As an effective scale for the condition assessment of patients with chronic ankle instability (CAI), the Cumberland Ankle Instability Tool (CAIT) is the most widely used scale, and its original version is written in English. Therefore, the purpose of our study is to apply the CAIT to Chinese patients and evaluate its responsiveness, reliability, and validity in terms of Chinese patients with CAI. First, we adapted the CAIT into the Chinese edition (CAIT-C), through which cross-cultural adaptation and translation can be carried out in a five-step procedure. Next, recruited patients completed the three periods of the Foot and Ankle Ability Measure (FAAM), CAIT-C, and the Medical Outcomes Study Short-Form 36 (SF-36) scales. Afterward, to assess the responsiveness, reliability, and validity, we calculated the standardized response mean (SRM), effect size (ES), Spearman's correlation coefficient (r), minimal detectable change (MDC), standard error of measurement (SEM), intraclass correlation coefficient (ICC), and Cronbach's alpha. Generally, in the use of CAI, 131, 119, and 86 patients favorably completed the three periods of the scales. The CAIT-C was proven to have good test-retest reliability (ICC = 0.930) and fine internal consistency (Cronbach's alpha = 0.845-0.878). The low-value of MDC (0.04-2.28) and SEM (1.73) show it is possible to detect clinical changes when we take advantage of CAIT-C. Good or moderate correlations (r = 0.422-0.738) were gained from the physical subscales of the SF-36 and the subscales of the FAAM and the CAIT-C. Fair or poor correlations (r = 0.003-0.360) were gained between the mental subscales of the SF-36 and the CAIT-C, which sufficiently indicated that the CAIT-C had good validity. Moreover, good responsiveness was observed in the CAIT-C (ES = 1.316, SRM = 1.418). The CAIT-C scale is an effective, valid, and reliable tool to evaluate Chinese CAI patients.
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http://dx.doi.org/10.1038/s41598-021-87848-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105356PMC
May 2021

AgroSeek: a system for computational analysis of environmental metagenomic data and associated metadata.

BMC Bioinformatics 2021 Mar 10;22(1):117. Epub 2021 Mar 10.

Department of Computer Science, Virginia Polytechnic Institute and State University, 24061, Blacksburg, USA.

Background: Metagenomics is gaining attention as a powerful tool for identifying how agricultural management practices influence human and animal health, especially in terms of potential to contribute to the spread of antibiotic resistance. However, the ability to compare the distribution and prevalence of antibiotic resistance genes (ARGs) across multiple studies and environments is currently impossible without a complete re-analysis of published datasets. This challenge must be addressed for metagenomics to realize its potential for helping guide effective policy and practice measures relevant to agricultural ecosystems, for example, identifying critical control points for mitigating the spread of antibiotic resistance.

Results: Here we introduce AgroSeek, a centralized web-based system that provides computational tools for analysis and comparison of metagenomic data sets tailored specifically to researchers and other users in the agricultural sector interested in tracking and mitigating the spread of ARGs. AgroSeek draws from rich, user-provided metagenomic data and metadata to facilitate analysis, comparison, and prediction in a user-friendly fashion. Further, AgroSeek draws from publicly-contributed data sets to provide a point of comparison and context for data analysis. To incorporate metadata into our analysis and comparison procedures, we provide flexible metadata templates, including user-customized metadata attributes to facilitate data sharing, while maintaining the metadata in a comparable fashion for the broader user community and to support large-scale comparative and predictive analysis.

Conclusion: AgroSeek provides an easy-to-use tool for environmental metagenomic analysis and comparison, based on both gene annotations and associated metadata, with this initial demonstration focusing on control of antibiotic resistance in agricultural ecosystems. Agroseek creates a space for metagenomic data sharing and collaboration to assist policy makers, stakeholders, and the public in decision-making. AgroSeek is publicly-available at https://agroseek.cs.vt.edu/ .
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http://dx.doi.org/10.1186/s12859-021-04035-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944603PMC
March 2021

Tungsten Hexanitride with Single-Bonded Armchairlike Hexazine Structure at High Pressure.

Phys Rev Lett 2021 Feb;126(6):065702

Department of Geological Sciences, Jackson School of Geosciences, The University of Texas at Austin, Austin, Texas 78712, USA.

WN_{6} phase discovered at 126-165 GPa after heating of W in nitrogen. XRD refinements reveal a unit cell in space group R3[over ¯]m which is consistent with the WN_{6} structure with armchairlike hexazine (N_{6}) rings, while strong A_{1g} Raman mode confirms its N─N single bonds. Density functional theory (DFT) calculations reveal balanced contributions of attractive interactions between W and covalent N_{6} rings, and repulsions between N_{6} rings that make WN_{6} ultrastiff and tough. The WN_{6} phase displays long bond lengths in the nearest N-N and pressure-enhanced electronic band gap, which pave the way for finding novel nitrides.
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http://dx.doi.org/10.1103/PhysRevLett.126.065702DOI Listing
February 2021

Lactic acid promotes metastatic niche formation in bone metastasis of colorectal cancer.

Cell Commun Signal 2021 01 21;19(1). Epub 2021 Jan 21.

College of Medicine, Southwest Jiaotong University, North Section 1 No.111, Second Ring Road, Chengdu, 610000, People's Republic of China.

Background: To investigate the effect of lactic acid (LA) on the progression of bone metastasis from colorectal cancer (CRC) and its regulatory effects on primary CD115 (+) osteoclast (OC) precursors.

Methods: The BrdU assay, Annexin-V/PI assay, TRAP staining and immunofluorescence were performed to explore the effect of LA on the proliferation, apoptosis and differentiation of OC precursors in vitro and in vivo. Flow cytometry was performed to sort primary osteoclast precursors and CD4(+) T cells and to analyze the change in the expression of target proteins in osteoclast precursors. A recruitment assay was used to test how LA and Cadhein-11 regulate the recruitment of OC precursors. RT-PCR and Western blotting were performed to analyze the changes in the mRNA and protein expression of genes related to the PI3K-AKT pathway and profibrotic genes. Safranin O-fast green staining, H&E staining and TRAP staining were performed to analyze the severity of bone resorption and accumulation of osteoclasts.

Results: LA promoted the expression of CXCL10 and Cadherin-11 in CD115(+) precursors through the PI3K-AKT pathway. We found that CXCL10 and Cadherin-11 were regulated by the activation of CREB and mTOR, respectively. LA-induced overexpression of CXCL10 in CD115(+) precursors indirectly promoted the differentiation of osteoclast precursors through the recruitment of CD4(+) T cells, and the crosstalk between these two cells promoted bone resorption in bone metastasis from CRC. On the other hand, Cadherin-11 mediated the adhesion between osteoclast precursors and upregulated the production of specific collagens, especially Collagen 5, which facilitated fibrotic changes in the tumor microenvironment. Blockade of the PI3K-AKT pathway efficiently prevented the progression of bone metastasis caused by lactate.

Conclusion: LA promoted metastatic niche formation in the tumor microenvironment through the PI3K-AKT pathway. Our study provides new insight into the role of LA in the progression of bone metastasis from CRC. Video Abstract.
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http://dx.doi.org/10.1186/s12964-020-00667-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818572PMC
January 2021

Colonization and bioweathering of monazite by Aspergillus niger: solubilization and precipitation of rare earth elements.

Environ Microbiol 2021 07 1;23(7):3970-3986. Epub 2021 Feb 1.

Geomicrobiology Group, School of Life Sciences, University of Dundee, Dundee, Scotland, DD1 5EH, UK.

Geoactive fungi play a significant role in bioweathering of rock and mineral substrates. Monazite is a phosphate mineral containing the rare earth elements (REE) cerium, lanthanum and neodymium. Little is known about geomicrobial transformations of REE-bearing minerals which are also relevant to REE biorecovery from terrestrial and extra-terrestrial reserves. The geoactive soil fungus Aspergillus niger colonized monazite in solid and liquid growth media without any apparent growth inhibition. In a glucose-minerals salts medium, monazite enhanced growth and mycelium extensively covered rock particle surfaces, probably due to the provision of phosphate and essential trace metals. Teeth-like and pagoda-like etching patterns indicated monazite dissolution, with extensive precipitation of secondary oxalate minerals. Biomechanical forces ensued causing aggressive bioweathering effects by tunnelling, penetration and splitting of the ore particles. High amounts of oxalic acid (~46 mM) and moderate amounts of citric acid (~5 mM) were produced in liquid media containing 2% (wt./vol.) monazite, and REE and phosphate were released. Correlation analysis suggested that citric acid was more effective than oxalic acid in REE mobilization, although the higher concentration of oxalic acid also implied complexant activity, as well as the prime role in REE-oxalate precipitation.
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http://dx.doi.org/10.1111/1462-2920.15402DOI Listing
July 2021

Spatial distribution and temporal change of antibiotics in soils amended with manure using two field application methods.

Sci Total Environ 2021 Mar 1;759:143431. Epub 2020 Nov 1.

School of Plant and Environmental Sciences, Virginia Tech, Blacksburg, VA 24061, USA. Electronic address:

Compared to surface application, manure subsurface injection significantly reduces transport of manure-associated antibiotics via surface runoff. However, the environmental fate of antibiotics in manure injection slits is unknown. A field investigation was conducted to monitor distribution and dissipation of pirlimycin, tylosin, chlortetracycline, and sulfamerazine in soil following either surface application or subsurface injection of liquid dairy manure. A simulated rainfall was conducted on days 0, 3, and 7 after manure application. Soil samples were collected before, on the day of, and 5, 14, 60, and 180 days after the simulated rainfall. Around an hour after manure application, antibiotic concentrations in injection slits were 4-49 and 4-26 times higher than those outside the slits and in surface application plots, respectively. Antibiotics concentrated in the injection slits for an extended time with limited horizontal and vertical movement, exposing the microbial community inside the slits to an elevated level of antibiotics. Dissipation of antibiotics was the fastest during the first 14 d after manure application before slowing down. There were no significant differences in antibiotic dissipation patterns in soils amended with manure using two application methods. Although the half-lives ranged from 3-11 d for pirlimycin, 3-10 d for sulfamerazine, 5-12 d for tylosin, and 3-21 day for chlortetracycline; pirlimycin, sulfamerazine, and tylosin remained detectable in soil even 180 d after the single manure application, indicating that soils could be a long-term source for antibiotics to the surrounding environment. Overall, in addition to resulting in less surface runoff of antibiotics from the fields, manure subsurface injection can also retain antibiotics in the injection slits and limit their movement overtime. However, more studies are needed to better understand if elevated levels of antibiotics, nutrients, organic matter, and water would result in "hot zones" for antibiotic resistance development in the manure subsurface injected fields.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143431DOI Listing
March 2021

Dietary fats suppress the peritoneal seeding of colorectal cancer cells through the TLR4/Cxcl10 axis in adipose tissue macrophages.

Signal Transduct Target Ther 2020 10 15;5(1):239. Epub 2020 Oct 15.

Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), 400038, Chongqing, China.

Peritoneal carcinomatosis (PC) of colorectal cancer (CRC) is a terminal phase of malignancy with no effective strategies for the prevention of this condition. Here we established PC models in mice by intraperitoneal engraftment of CRC cells and revealed an unexpected role for a high-fat diet (HFD) in preventing metastatic seeding in the visceral fat. Mechanistically, the HFD stimulated the activation of adipose tissue macrophages (ATMs) toward an M1-like phenotype and enhanced ATM tumor phagocytosis in a TLR4-dependent manner. Furthermore, the TLR4-Cxcl10 axis in ATMs promoted T cell recruitment, and M1-like macrophages stimulated T cell activation in tumor-seeded fats. The inhibitory effect of the HFD on tumor seeding was abolished with the ablation of macrophages, inactivation of T cells, or blockade of the TLR4-Cxcl10 axis in macrophages. Finally, we showed that a HFD and conventional chemotherapeutic agents (oxaliplatin or 5-fluorouracil) synergistically improved the survival of tumor-seeded mice. Collectively, our findings demonstrate that peritoneal seeding of CRC can be suppressed by short-term treatment with a HFD in the early phase, providing a novel concept for the management of these patients in the clinic.
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http://dx.doi.org/10.1038/s41392-020-00327-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566605PMC
October 2020

Validation of Predictors of Disease Severity and Outcomes in COVID-19 Patients: A Descriptive and Retrospective Study.

Med (N Y) 2020 Dec 19;1(1):128-138.e3. Epub 2020 May 19.

Department of Biochemistry and Molecular Biology, Third Military Medical University (Army Medical University), Chongqing 400038, People's Republic of China.

Background: The severity and outcome of COVID-19 cases has been associated with the percentage of circulating lymphocytes (LYM%), levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin (PCT), lactic acid (LA), and viral load (ORF1ab Ct). However, the predictive power of each of these indicators in disease classification and prognosis remains largely unclear.

Methods: We retrospectively collected information on the above parameters in 142 patients with COVID-19, stratifying them by survival or disease severity.

Findings: CRP, PCT, IL-6, LYM%, and ORF1ab Ct were significantly altered between survivors and non-survivors. LYM%, CRP, and IL-6 were the most sensitive and reliable factors in distinguishing between survivors and non-survivors. These indicators were significantly different between critically ill and severe/moderate patients. Only LYM% levels were significantly different between severe and moderate types. Among all the investigated indicators, LYM% was the most sensitive and reliable in discriminating between critically ill, severe, and moderate types and between survivors and non-survivors.

Conclusions: CRP, PCT, IL-6, LYM%, and ORF1ab Ct, but not LA, could predict prognosis and guide classification of COVID-19 patients. LYM% was the most sensitive and reliable predictor for disease typing and prognosis. We recommend that LYM% be further investigated in the management of COVID-19.

Funding: This study was supported in part by awards from the National Natural Science Foundation of China, the Foundation and Frontier Research Project of Chongqing, and the Chongqing Youth Top Talent Project.
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http://dx.doi.org/10.1016/j.medj.2020.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7235581PMC
December 2020

Changes of root microbial populations of natively grown plants during natural attenuation of V-Ti magnetite tailings.

Ecotoxicol Environ Saf 2020 Sep 7;201:110816. Epub 2020 Jun 7.

College of Resources, Sichuan Agricultural University, Chengdu, 611130, China. Electronic address:

Mine tailings contain dangerously high levels of toxic metals which pose a constant threat to local ecosystems. Few naturally grown native plants can colonize tailings site and the existence of their root-associated microbial populations is poorly understood. The objective of this study was to give further insights into the interactions between native plants and their microbiota during natural attenuation of abandoned V-Ti magnetite mine tailings. In the present work, we first examined the native plants' potential for phytoremediation using plant/soil analytical methods and then investigated the root microbial communities and their inferred functions using 16 S rRNA-based metagenomics. It was found that in V-Ti magnetite mine tailings the two dominant plants Bothriochloa ischaemum and Typha angustifolia were able to increase available nitrogen in the rhizosphere soil by 23.3% and 53.7% respectively. The translocation factors (TF) for both plants indicated that B. ischaemum was able to accumulate Pb (TF = 1.212), while T. angustifolia was an accumulator of Mn (TF = 2.502). The microbial community structure was more complex in the soil associated with T. angustifolia than with B. ischaemum. The presence of both plants significantly reduced the population of Acinetobacter. Specifically, B. ischaemum enriched Massilia, Opitutus and Hydrogenophaga species while T. angustifolia significantly increased rhizobia species. Multivariate analyses revealed that among all tested soil variables Fe and total organic carbon (TOC) could be the key factors in shaping the microbial structure. The putative functional analysis indicated that soil sample of B. ischaemum was abundant with nitrate/nitrite reduction-related functions while that of T. angustifolia was rich in nitrogen fixing functions. The results indicate that these native plants host a diverse range of soil microbes, whose community structure can be shaped by plant types and soil variables. It is also possible that these plants can be used to improve soil nitrogen content and serve as bioaccumulators for Pb or Mn for phytoremediation purposes.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110816DOI Listing
September 2020

Colorectal cancer cells promote osteoclastogenesis and bone destruction through regulating EGF/ERK/CCL3 pathway.

Biosci Rep 2020 06;40(6)

College of Medicine, Southwest Jiaotong University, North Section 1 No. 111, Second Ring Road, Chengdu 610000, China.

Bone metastasis of colorectal cancer (CRC) cells leads to osteolysis. Aberrant activation of osteoclasts is responsible for bone resorption in tumor. In general, bone marrow-derived monocytes (BMMs) differentiate into osteoclasts, however, how CRC cells interact with BMMs and how to regulate the differentiation is elusive. We here report that CRC cells promote bone resorption in bone metastasis. Transcriptomic profiling revealed CCL3 up-regulated in MC-38 conditional medium treated BMMs. Further investigation demonstrated that CCL3 produced by BMMs facilitated cell infusion and thus promoted the osteoclastogenesis. In addition, CRC cells derived EGF stimulated the production of CCL3 in BMMs through activation of ERK/CREB pathway. Blockage of EGF or CCL3 can efficiently attenuate the osteolysis in bone metastasis of CRC.
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http://dx.doi.org/10.1042/BSR20201175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315727PMC
June 2020

A microfluidics-derived growth factor gradient in a scaffold regulates stem cell activities for tendon-to-bone interface healing.

Biomater Sci 2020 Jul 27;8(13):3649-3663. Epub 2020 May 27.

Center of Sports Medicine of Orthopaedic Department, Southwest hospital, Third Military Medical University, Chongqing 400038, China.

Treatment of tendon-to-bone interface injury has long been challenging in sports medicine. The major obstacle lies with the complicated three-layer structure of the tissue that consists of a bone region with osteocytes, a tendon region with tenocytes and a transitional region with chondrocytes. Conventional tissue engineering approaches using simply biomaterial scaffolds, stem cells and combinations of them had limited abilities to reconstruct the gradient structure with normal biomechanical properties. We herein aim to construct a three-layer structure with bone marrow-derived stem cells and tendon stem cells cultured in a decellularized tendon scaffold, through application of a gradient of biological cues in the longitudinal direction of the scaffold that guides the stem cells to differentiate and remodel the extracellular matrix in response to different medium concentrations in different regions. A microfluidic chip, on which a tree-like flow pattern was implemented, was adopted to create the concentration gradient in a dichotomous manner. We screened for an optimized seeding ratio between the two stem cell types before incubation of the scaffold in the medium concentration gradient and surgical implantation. Histology and immunohistochemistry assessments, both qualitatively and semi-quantitatively, showed that the microfluidic system provided desired guidance to the seeded stem cells that the healing at 8-week post-implantation presented a similar structure to that of a normal tendon-to-bone interface, which was outstanding compared to treatments without gradient guidance, stem cells or scaffolds where chaotic and fibrotic structures were obtained. This strategy offers a potentially translational tissue engineering approach for better outcomes in tendon-to-bone healing.
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http://dx.doi.org/10.1039/d0bm00229aDOI Listing
July 2020

Exosomes Derived from Bone Marrow Stromal Cells (BMSCs) Enhance Tendon-Bone Healing by Regulating Macrophage Polarization.

Med Sci Monit 2020 May 5;26:e923328. Epub 2020 May 5.

Sports Medicine Center, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing, China (mainland).

BACKGROUND Inflammation after tendon-bone junction injury results in the formation of excessive scar tissue and poor biomechanical properties. Recent research has shown that exosomes derived from bone marrow stromal cells (BMSCs) can modulate inflammation during tissue healing. Thus, our study aimed to enhance tendon-bone healing by use of BMSC-derived exosomes (BMSC-Exos). MATERIAL AND METHODS The mouse tendon-bone reconstruction model was established, and the mice were randomly divided into 3 groups: the control group, the hydrogel group, and the hydrogel+exosome group, with 30 mice in each group. At 7 days, 14 days, and 1 month after surgery, tendon-bone junction samples were harvested, and the macrophage polarization and tendon-bone healing were evaluated based on histology, immunofluorescence, and quantitative RT-PCR (qRT-PCR) analysis. RESULTS In the early phase, we observed significantly higher numbers of M2 macrophages and more anti-inflammatory and chondrogenic-related factors in the hydrogel+BMSC-Exos group compared with the control group and the hydrogel group. The M1 macrophages and related proinflammatory factors decreased. Cell apoptosis decreased in the hydrogel+BMSC-Exos group, while cell proliferation increased; in particular, the CD146+ stem cells substantially increased. At 1 month after surgery, there was more fibrocartilage in the hydrogel+BMSC-Exos group than in the other groups. Biomechanical testing showed that the maximum force, strength, and elastic modulus were significantly improved in the hydrogel+BMSC-Exos group. CONCLUSIONS Our study provides evidence that the local administration of BMSC-Exos promotes the formation of fibrocartilage by increasing M2 macrophage polarization in tendon-to-bone healing, leading to improved biomechanical properties. These findings provide a basis for the potential clinical use of BMSC-Exos in tendon-bone repair.
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http://dx.doi.org/10.12659/MSM.923328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218969PMC
May 2020

The Agpat4/LPA axis in colorectal cancer cells regulates antitumor responses via p38/p65 signaling in macrophages.

Signal Transduct Target Ther 2020 03 27;5(1):24. Epub 2020 Mar 27.

Department of Biochemistry and Molecular Biology, Southwest Medical University, Luzhou, 646000, China.

Lipid metabolic reprogramming plays an essential role in regulating the progression of colorectal cancer (CRC). However, the effect of lysophosphatidic acid (LPA) metabolism on CRC development is incompletely characterized. Here, we compared the mRNA levels of human CRC tissues to those of paracarcinoma tissues and focused on the notably enriched LPA metabolic pathways. We identified and verified that 1-acylglycerol-3-phosphate O-acyltransferase 4 (Agpat4) was aberrantly expressed in CRC tissues and predicted poor survival in CRC patients. Manipulating Agpat4 expression in CRC cells did not affect the growth or migration of CRC cells in vitro, whereas Agpat4 silencing suppressed CRC cell growth in subcutaneous and peritoneal xenograft models. Mechanistically, Agpat4 silencing-induced LPA release from CRC cells and polarized macrophages to an M1-like phenotype through LPA receptors 1 and 3. This M1 activation, characterized by elevated p38/p65 signaling and increased proinflammatory cytokines, promoted the infiltration and activation of CD4 and CD8 T cells in the tumor microenvironment. Modulation of the Agpat4/LPA/p38/p65 axis regulated macrophage polarization, T-cell activity and CRC progression. Notably, combined therapy with LPA and regular chemotherapy drugs synergistically suppressed CRC development. Taken together, our results showed that the Agpat4/LPA axis in CRC cells regulated p38/p65 signaling-dependent macrophage polarization, T-cell activation, and CRC progression. The Agpat4/LPA/p38/p65 axis might represent a potential target for therapy in the clinic.
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http://dx.doi.org/10.1038/s41392-020-0117-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7099097PMC
March 2020

Monazite transformation into Ce- and La-containing oxalates by Aspergillus niger.

Environ Microbiol 2020 04 13;22(4):1635-1648. Epub 2020 Mar 13.

Geomicrobiology Group, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland, UK.

Monazite is a naturally occurring lanthanide (Ln) phosphate mineral [Ln (PO ) ] and is the main industrial source of the rare earth elements (REE), cerium and lanthanum. Endeavours to ensure the security of supply of elements critical to modern technologies view bioprocessing as a promising alternative or adjunct to new methods of element recovery. However, relatively little is known about microbial interactions with REE. Fungi are important geoactive agents in the terrestrial environment and well known for properties of mineral transformations, particularly phosphate solubilization. Accordingly, this research examined the capability of a ubiquitous geoactive soil fungus, Aspergillus niger, to affect the mobility of REE in monazite and identify possible mechanisms for biorecovery. It was found that A. niger could grow in the presence of monazite and mediated the formation of secondary Ce and La-containing biominerals with distinct morphologies including thin sheets, orthorhombic tablets, acicular needles, and rosette aggregates which were identified as cerium oxalate decahydrate (Ce (C O ) ·10H O) and lanthanum oxalate decahydrate (La (C O ) ·10H O). In order to identify a means for biorecovery of REE via oxalate precipitation the bioleaching and bioprecipitation potential of biomass-free spent culture supernatants was investigated. Although such indirect bioleaching of REE was low from the monazite with maximal lanthanide release reaching >40 mg L , leached REE were efficiently precipitated as Ce and La oxalates of high purity, and did not contain Nd, Pr and Ba, present in the original monazite. Geochemical modelling of the speciation of oxalates and phosphates in the reaction system confirmed that pure Ln oxalates can be formed under a wide range of chemical conditions. These findings provide fundamental knowledge about the interactions with and biotransformation of REE present in a natural mineral resource and indicate the potential of oxalate bioprecipitation as a means for efficient biorecovery of REE from solution.
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http://dx.doi.org/10.1111/1462-2920.14964DOI Listing
April 2020

Fate of pirlimycin and antibiotic resistance genes in dairy manure slurries in response to temperature and pH adjustment.

Sci Total Environ 2020 Mar 26;710:136310. Epub 2019 Dec 26.

Department of Statistics, Virginia Tech, Blacksburg, VA, USA.

Quantifying the fate of antibiotics and antibiotic resistance genes (ARGs) in response to physicochemical factors during storage of manure slurries will aid in efforts to reduce the spread of resistance when manure is land-applied. The objectives of this study were to determine the effects of temperature (10, 35, and 55 °C) and initial pH (5, 7, 9, and 12) on the removal of pirlimycin and prevalence of ARGs during storage of dairy manure slurries. We collected and homogenized feces and urine from five lactating dairy cows treated with pirlimycin and prepared slurries by mixing manure and sterile water. Aliquots (200 mL) of slurry were transferred and incubated in 400 mL glass beakers under different temperatures (10, 35, and 55 °C) or initial pH (5, 7, 9, and 12). Pirlimycin concentration and abundances of 16S rRNA, mefA, tet(W), and cfxA as indicators of total bacteria and ARGs corresponding to macrolide, tetracycline, and β-lactam resistance, respectively, were analyzed during manure incubation. The thermophilic environment (55 °C) increased the deconjugation and removal of pirlimycin, while the acidic shock at pH 5 increased deconjugation but inhibited removal of pirlimycin, suggesting that the chemical stability of pirlimycin could be affected by temperature and pH. The thermophilic environment decreased mefA relative abundance on day 7 and 28 (P = 0.02 and 0.04), which indicates that the bacteria that encoded mefA gene were not thermotolerant. Although mefA relative abundance was greater at the pH 9 shock than the rest of pH treatments on day 7 (P = 0.04), no significant pH effect was observed on day 28. The tet(W) abundance under initial pH 12 shock was less than other pH shocks on day 28 (P = 0.01), while no temperature effect was observed on day 28. There was no significant temperature and initial pH effect on cfxA abundance at any time point during incubation, implying that the bacteria that carrying cfxA gene are relatively insensitive to these environmental factors. Overall, directly raising temperature and pH can facilitate pirlimycin removal and decrease mefA and tet(W) relative abundances during storage of manure slurries.
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http://dx.doi.org/10.1016/j.scitotenv.2019.136310DOI Listing
March 2020

A Roadmap for the Development of Ivermectin as a Complementary Malaria Vector Control Tool.

Am J Trop Med Hyg 2020 02;102(2s):3-24

US President’s Malaria Initiative/US Centers for Disease Control and Prevention

In the context of stalling progress against malaria, resistance of mosquitoes to insecticides, and residual transmission, mass drug administration (MDA) of ivermectin, an endectocide used for neglected tropical diseases (NTDs), has emerged as a promising complementary vector control method. Ivermectin reduces the life span of mosquitoes that feed on treated humans and/or livestock, potentially decreasing malaria parasite transmission when administered at the community level. Following the publication by WHO of the preferred product characteristics for endectocides as vector control tools, this roadmap provides a comprehensive view of processes needed to make ivermectin available as a vector control tool by 2024 with a completely novel mechanism of action. The roadmap covers various aspects, which include 1) the definition of optimal dosage/regimens for ivermectin MDA in both humans and livestock, 2) the risk of resistance to the drug and environmental impact, 3) ethical issues, 4) political and community engagement, 5) translation of evidence into policy, and 6) operational aspects of large-scale deployment of the drug, all in the context of a drug given as a prevention tool acting at the community level. The roadmap reflects the insights of a multidisciplinary group of global health experts who worked together to elucidate the path to inclusion of ivermectin in the toolbox against malaria, to address residual transmission, counteract insecticide resistance, and contribute to the end of this deadly disease.
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http://dx.doi.org/10.4269/ajtmh.19-0620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008306PMC
February 2020

Short communication: Increasing temperature and pH can facilitate reductions of cephapirin and antibiotic resistance genes in dairy manure slurries.

J Dairy Sci 2020 Mar 15;103(3):2877-2882. Epub 2020 Jan 15.

Department of Dairy Science, Virginia Tech, Blacksburg 24061.

Quantifying antibiotics and antibiotic resistance genes (ARG) in manure exposed to various temperature and pH treatments could guide the development of cost-effective manure handling methods to minimize the spread of antibiotic resistance following land application of manure. This study aimed to investigate the effect of various temperatures and initial pH shocks on the persistence of a cephalosporin antibiotic and ARG in dairy manure slurries. Feces and urine were collected from 5 healthy dairy cows administered with cephapirin (cephalosporin antibiotic) at dry-off via intramammary infusion and were mixed with sterile water to generate manure slurries. In a 28-d incubation study, dairy manure slurries either were continuously exposed to 1 of 3 temperatures (10, 35, and 55°C) or received various initial pH (5, 7, 9, and 12) shocks. Cephapirin was detected in the initial samples and on d 1 following all treatments, but it was undetectable thereafter. This indicates that cephapirin can be rapidly degraded irrespective of temperature and pH treatments. However, degradation was greater on d 1 with the mesophilic (35°C) and thermophilic (55°C) environments compared with the psychrophilic environment (10°C). Increasing pH beyond neutral also accelerated degradation as cephapirin concentrations were lower on d 1 after initial alkaline adjustments (pH 9 and 12) than after neutral and acidic adjustments (pH 7 and 5). No significant effect of temperature or initial pH was observed on abundances of a β-lactam ARG, cfxA, and a tetracycline ARG, tet(W), implying that bacteria that encoded cfxA or tet(W) genes were not sensitive to temperature or pH in dairy manure slurries. However, abundances of a macrolide ARG, mefA, were decreased in the psychrophilic and thermophilic environments and also following exposure to a strong alkaline shock (pH 12). Our results suggest that increasing temperature or pH during storage of dairy manure slurries could be used together with other on-farm practices that are tailored to reduce the transfer of ARG from manure to the environment following land application.
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http://dx.doi.org/10.3168/jds.2019-17453DOI Listing
March 2020

Effect of mangrove species on removal of tetrabromobisphenol A from contaminated sediments.

Chemosphere 2020 Apr 18;244:125385. Epub 2019 Nov 18.

Key Laboratory of Ministry of Education for Coastal and Wetland Ecosystems, College of the Environment and Ecology, Xiamen University, Xiamen, 361102, China; State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, 361102, China. Electronic address:

The increase levels of tetrabromobisphenol A (TBBPA) in mangrove wetlands is of concern due to its potential toxic impacts on ecosystem. A 93-day greenhouse pot experiment was conducted to investigate the effects of mangrove plants, A. marina and K. obovata, on TBBPA degradation in sediment and to reveal the associated contributing factor(s) for its degradation. Results show that both mangrove species could uptake, translocate, and accumulate TBBPA from mangrove sediments. Compared to the unplanted sediment, urease and dehydrogenase activity as well as total bacterial abundance increased significantly (p < 0.05) in the sediment planted with mangrove plants, especially for K. obovata. In the mangrove-planted sediment, the Anaerolineae genus was the dominant bacteria, which has been reported to enhance TBBPA dissipation, and its abundance increased significantly in the sediment at early stage (0-35 day) of the greenhouse experiment. Compared to A. marina-planted sediment, higher enrichment of Geobater, Pseudomonas, Flavobacterium, Azoarcus, all of which could stimulate TBBPA degradation, was observed for the K. obovata-planted sediment during the 93-day growth period. Our mass balance result has suggested that plant-induced TBBPA degradation in the mangrove sediment is largely due to elevated microbial activities and total bacterial abundance in the rhizosphere, rather than plant uptake. In addition, different TBBPA removal efficiencies were observed in the sediments planted with different mangrove species. This study has demonstrated that K. obovata is a more suitable mangrove species than A. marina when used for remediation of TBBPA-contaminated sediment.
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http://dx.doi.org/10.1016/j.chemosphere.2019.125385DOI Listing
April 2020

On the mechanism of antibiotic resistance and fecal microbiota transplantation.

Math Biosci Eng 2019 08;16(6):7057-7084

School of Mathematical Sciences, Soochow University, Suzhou 215006, P. R. China.

Antibiotic resistance is a growing threat to human health and is caused by mainly the overuse of antibiotics in clinical medicine. Clinically, drug resistance emerges after a series of antibiotic treatments, implying that each treatment changes the intestinal flora composition and the accumulations of these changes induce the resistance. But mathematically, this cumulative effect cannot be achieved by a general population model, because the system will return to its pre-treatment state (an isolated steady state) after each cure. Based on the fact that sensitive bacteria and resistant bacteria are similar in most respects except their reactions to antibiotics, we developed a mathematical model with a specific phase-space structure: instead of isolated points, the steady states of this system compose one-dimensional manifolds (line segments). This structure explains the fundamental mechanism of antibiotic resistance: after antibiotic treatment, the system cannot return to the pretreatment healthy steady state but rather slightly moves along the manifold to a different steady state. Each use of antibiotics can change the ratio of resistant to susceptible pathogens in the host. The change the ratio can persist and accumulate, and finally promotes the emergence of antimicrobial resistance. We also assessed key factors (such as pathogen composition, the amount and composition of beneficial bacteria, medication duration and bactericidal rates of drugs) influencing the development of drug resistance. In addition, we clarified how fecal microbiota transplantation affects the treatment of antibiotic-resistant infections. The effect is essentially a transfer towards the healthy state in the phase space. Finally, based on the mechanisms revealed by the mathematical models, we suggested some strategies to delay or prevent the emergence of drug resistance. These findings not only provide a solid theoretical basis for the treatment of antimicrobial resistance, but also inspire clues to the phenomenon of drug resistance.
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http://dx.doi.org/10.3934/mbe.2019354DOI Listing
August 2019

Aspirin promotes tenogenic differentiation of tendon stem cells and facilitates tendinopathy healing through regulating the GDF7/Smad1/5 signaling pathway.

J Cell Physiol 2020 05 21;235(5):4778-4789. Epub 2019 Oct 21.

Department of Orthopeadics/Sports Medicine Center, State Key Laboratory of Trauma, Burn and Combined Injury, Southwest Hospital, Third Military Medical University, Chongqing, China.

Tendinopathy is a common musculoskeletal system disorder in sports medicine, but regeneration ability of injury tendon is limited. Tendon stem cells (TSCs) have shown the definitive treatment evidence for tendinopathy and tendon injuries due to their tenogenesis capacity. Aspirin, as the representative of nonsteroidal anti-inflammatory drugs for its anti-inflammatory and analgestic actions, has been commonly used in treating tendinopathy in clinical, but the effect of aspirin on tenogenesis of TSCs is unclear. We hypothesized that aspirin could promote injury tendon healing through inducing TSCs tenogenesis. The aim of the present study is to make clear the effect of aspirin on TSC tenogenesis and tendon healing in tendinopathy, and thus provide new treatment evidence and strategy of aspirin for clinical practice. First, TSCs were treated with aspirin under tenogenic medium for 3, 7, and 14 days. Sirius Red staining was performed to observe the TSC differentiation. Furthermore, RNA sequencing was utilized to screen out different genes between the induction group and aspirin treatment group. Then, we identified the filtrated molecules and compared their effect on tenogenesis and related signaling pathway. At last, we constructed the tendinopathy model and compared biomechanical changes after aspirin intake. From the results, we found that aspirin promoted tenogenesis of TSCs. RNA sequencing showed that growth differentiation factor 6 (GDF6), GDF7, and GDF11 were upregulated in induction medium with the aspirin group compared with the induction medium group. GDF7 increased tenogenesis and activated Smad1/5 signaling. In addition, aspirin increased the expression of TNC, TNMD, and Scx and biomechanical properties of the injured tendon. In conclusion, aspirin promoted TSC tenogenesis and tendinopathy healing through GDF7/Smad1/5 signaling, and this provided new treatment evidence of aspirin for tendinopathy and tendon injuries.
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http://dx.doi.org/10.1002/jcp.29355DOI Listing
May 2020

Plasma metabolite profiling reveals potential biomarkers of giant cell tumor of bone by using NMR-based metabolic profiles: A cross-sectional study.

Medicine (Baltimore) 2019 Oct;98(40):e17445

Department of Orthopedics.

Giant cell tumor (GCT) of bone is a locally aggressive bone tumor, which accounts for 4% to 5% of all primary bone tumors. At present, the early diagnosis and postoperative recurrence monitoring are still more difficult due to the lack of effective biomarkers in GCT. As an effective tool, metabolomics has played an essential role in the biomarkers research of many tumors. However, there has been no related study of the metabolomics of GCT up to now. The purpose of this study was to identify several key metabolites as potential biomarkers for GCT by using nuclear magnetic resonance (NMR)-based metabolic profiles.Patients with GCT in our hospital were recruited in this study and their plasma was collected as the research sample, and plasma collected from healthy subjects was considered as the control. NMR was then utilized to detect all samples. Furthermore, based on correlation coefficients, variable importance for the projection values and P values of metabolites obtained from multidimensional statistical analysis, the most critical metabolites were selected as potential biomarkers of GCT. Finally, relevant metabolic pathways involved in these potential biomarkers were determined by database retrieval, based on which the metabolic pathways were plotted.Finally, 28 GCT patients and 26 healthy volunteers agreed to participate in the study. In the multidimensional statistical analysis, all results showed that there was obvious difference between the GCT group and the control group. Ultimately, 18 metabolites with significant differences met the selection condition, which were identified as potential biomarkers. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) and Human Metabolome Database (HMD) database searching and literature review, these metabolites were found to be mainly correlated with glucose metabolism, fat metabolism, amino acid metabolism, and intestinal microbial metabolism. These metabolic disorders might, in turn, reflect important pathological processes such as proliferation and migration of tumor cells and immune escape in GCT.Our work showed that these potential biomarkers identified appeared to have early diagnostic and relapse monitoring values for GCT, which deserve to be further investigated. In addition, it also suggested that metabolomics profiling approach is a promising screening tool for the diagnosis and relapse monitoring of GCT patients.
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http://dx.doi.org/10.1097/MD.0000000000017445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6783185PMC
October 2019

Predictions on High-Power Trivalent Metal Pentazolate Salts.

J Phys Chem Lett 2019 Oct 1;10(20):6166-6173. Epub 2019 Oct 1.

National Laboratory of Solid State Microstructures, School of Physics and Collaborative Innovation Center of Advanced Microstructures , Nanjing University , Nanjing 210093 , China.

High-energy-density materials (HEDMs) have been intensively studied for their significance in fundamental sciences and practical applications. Here, using the molecular crystal structure search method based on first-principles calculations, we have predicted a series of metastable energetic trivalent metal pentazolate salts MN (M= Al, Ga, Sc, and Y). These compounds have high energy densities, with the highest nitrogen content among the studied nitrides so far. Pentazolate N molecules stack up face-to-face and form wave-like patterns in the 222 and symmetries. The strong covalent bonding and very weak noncovalent interactions with nonbonded overlaps coexist in these ionic-like structures. We find MN molecular structures are mechanically stable up to high temperature (∼1000 K) and ambient pressure. More importantly, these trivalent metal pentazolate salts have high detonation pressure (∼80 GPa) and velocity (∼12 km/s). Their detonation pressures exceeding that of TNT and HMX make them good candidates for high-brisance green energetic materials.
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http://dx.doi.org/10.1021/acs.jpclett.9b02383DOI Listing
October 2019

[Mid-term effectiveness of arthrolysis and hinged external fixation for treatment of stiff elbow caused by heterotrophic ossification].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2019 Oct;33(10):1299-1304

Department of Orthopedics/Sports Medicine Center, the First Affiliated Hospital of Army Medical University of Chinese PLA, Chongqing, 445000,

Objective: To evaluate the mid-term effectiveness of arthrolysis and hinged external fixation for the treatment of stiff elbow caused by heterotrophic ossification.

Methods: Between January 2014 and December 2017, 11 patients with stiff elbow caused by heterotrophic ossification were admitted. There were 9 males and 2 females with an average age of 32 years (range, 14-48 years), and left side in 6 cases and right side in 5 cases. The cause of stiff elbow included humerus fracture in 5 cases, ulna fracture in 2 cases, fracture of capitulum radii in 1 case, dislocation of capitulum radii in 1 case, terrible triad of the elbow in 1 case, and soft tissue injury in 1 case. The disease duration ranged from 7 to 18 months (mean, 11 months). Preoperative active range of motion of elbow was (19.6±17.5)° and Mayo score was 34.1±9.7. All patients received the treatment of arthrolysis and debridement of heterotrophic ossification lesion combining hinged external fixator, and active and passive rehabilitation with the help of hinged external fixator. The hinged external fixators were removed after 2 months.

Results: All patients were followed up 13-36 months (mean, 19.1 months). All incisions healed by first intention, and no complication of infection or nerve lesion occurred postoperatively. At last follow-up, the results of X-ray films showed that no heterotrophic ossification recurred. The active range of motion of elbow was (116.4±16.6)° and Mayo score was 93.2±7.8, showing significant differences when compared with preoperative ones ( =17.508, =0.000; =16.618, =0.000).

Conclusion: The application of arthrolysis and debridement of heterotrophic ossification lesion combining hinged external fixator can improve the elbow's range of motion significantly and obtain a good mid-term effectiveness.
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http://dx.doi.org/10.7507/1002-1892.201902002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8337636PMC
October 2019
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