Publications by authors named "Xiang Cheng"

500 Publications

Patients' perception of the outpatient pharmaceutical service quality in hospital pharmacies with auditable pharmaceutical transactions and services in Ethiopia: a cross-sectional study.

BMJ Open 2021 May 4;11(5):e042853. Epub 2021 May 4.

Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmacy, Xi'an Jiaotong University, Xi'an, China

Objective: To ensure the availability of quality pharmaceutical products and effective pharmaceutical services, a package of interventions named auditable pharmaceutical transactions and services (APTS), was implemented in the tertiary and secondary hospitals across Ethiopia since 2014. This study aimed to evaluate outpatients' perception of pharmaceutical service quality in hospitals with APTS in Ethiopia.

Design: Cross-sectional study.

Setting: Seven hospitals of Tigray, Ethiopia.

Participants: 794 patients coming for pharmaceutical services.

Main Outcome Measures: SERVQUAL instrument was employed to collect the patient's perception of pharmaceutical services. The mean perception score of pharmaceutical service quality was the main outcome measurement.

Results: Out of 810 patients approached, 794 participated in the study (response rate of 98.02%). Overall, the mean perception score of the service quality was 3.1 of 5. Among the five dimensions of SERVQUAL, dimension of empathy achieved the highest result with a mean score of 3.71, and tangibility was the second (3.19), followed by responsiveness (3.08), assurance (2.87) and reliability (2.81). The perception of patients in tertiary hospitals of service quality was more positive compared with patients in secondary hospitals (3.265>3.011, p=0.04). However, the difference was only significant in the dimension of assurance when considering the five dimensions separately. Respondents who were older, widowed, illiterate, farmer, retired or Orthodox were found to have better quality service experience compared with others (p=0.001).

Conclusion: Generally, outpatients' perception of pharmaceutical service quality was positive. However, two dimensions of the service quality (assurance and reliability) were negatively perceived. To improve the service quality, we recommended the following: (1) managers should provide more training for pharmacists to strengthen their professional knowledge and encourage them to cooperate with other professionals; (2) the government needs to develop guidelines on information provided to patients and train the pharmacists to follow them; (3) hospitals can apply various procurement methods and efficient inventory management methods.
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http://dx.doi.org/10.1136/bmjopen-2020-042853DOI Listing
May 2021

Total parathyroidectomy with forearm autotransplantation in secondary hyperparathyroidism patients: analysis of muscle, subcutaneous and muscle + subcutaneous method.

BMC Surg 2021 May 1;21(1):226. Epub 2021 May 1.

Department of Thyroid Surgery, The Second Affiliated Hospital of Zhejiang University College of Medicine, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.

Background: Forearm autotransplantation after parathyroidectomy has turned into the standard method for secondary hyperparathyroidism (SHPT) treatment in chronic kidney disease patients. Our study aimed to explore the effects of three methods including muscle, subcutaneous and muscle + subcutaneous transplant methods on SHPT.

Methods: Seventy five SHPT patients were enrolled and assigned into the muscle + subcutaneous (M + S) (n = 26), muscle (M) (n = 35), and subcutaneous (S) (n = 14) groups. The operation efficacy evaluation included preoperative and postoperative biological characteristics such as parathyroid hormone (PTH), serum phosphorus, serum calcium and alkaline phosphatase (ALP). The data were recorded from pre-operation time point to 1, 2, 3, 6, 12, 18, 24 month (mo) postoperation periods. After operation, short-form health survey (SF-36) scores was made for life quality identification at 1, 2, 3, 6, 12, 24 time points. Symptoms about SHPT including bone pain, fracture, pruritus, and coronary artery calcification were followed-up based on the scale.

Results: Compared with the preoperative record, all the M + S, M, and S groups showed postoperative decreased levels of PTH, serum phosphorus, serum calcium, calcium-phosphorus. In M + S group, the PTH and serum calcium level kept more steady compared with the M and S groups during a 24 mo duration observation. After this, a SF-36 score scale which represents the life quality show M + S group got more scores at 3, 6, 12, 18 and 24 mo points. At last, the incidence of SHPT associated symptoms including Bone pain, Fracture, Pruritus, and Coronary artery calcification in M + S group were decreased compared with M and S groups at 1, 3, 6, 12 and 24 mo post-operation time points.

Conclusion: M + S seems to be an efficient method for medical treatment of SHPT patients in the control of PTH and serum calcium. This mixed transplant strategy improves the biochemical characterizes compared with M and S groups in SHPT patients. Furthermore, the M + S method make beneficial on clinical outcomes and life quality of patients.
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http://dx.doi.org/10.1186/s12893-021-01222-2DOI Listing
May 2021

Multicomponent Synthesis of Unsymmetrical 4,5-Disubstituted Imidazolium Salts as N-Heterocyclic Carbene Precursors: Applications in Palladium-Catalyzed Cross-Coupling Reactions.

J Org Chem 2021 Apr 28. Epub 2021 Apr 28.

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.

Various novel (a)chiral 4,5-disubstituted 1-aryl-3-alkyl-imidazolium salts were synthesized via the multicomponent reaction of diketone derivatives, sterically congested arylamines, and alkylamines. Moreover, two novel unsymmetrical bulky cycloalkyl-based NHC-Pd complexes proved highly active as catalysts for Suzuki-Miyaura and Negishi cross-coupling reactions.
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http://dx.doi.org/10.1021/acs.joc.1c00075DOI Listing
April 2021

Imaging the emergence of bacterial turbulence: Phase diagram and transition kinetics.

Sci Adv 2021 Apr 23;7(17). Epub 2021 Apr 23.

Department of Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN 55455, USA.

We experimentally study the emergence of collective bacterial swimming, a phenomenon often referred to as bacterial turbulence. A phase diagram of the flow of 3D suspensions spanned by bacterial concentration, the swimming speed of bacteria, and the number fraction of active swimmers is systematically mapped, which shows quantitative agreement with kinetic theories and demonstrates the dominant role of hydrodynamic interactions in bacterial collective swimming. We trigger bacterial turbulence by suddenly increasing the swimming speed of light-powered bacteria and image the transition to the turbulence in real time. Our experiments identify two unusual kinetic pathways, i.e., the one-step transition with long incubation periods near the phase boundary and the two-step transition driven by long-wavelength instabilities deep inside the turbulent phase. Our study provides not only a quantitative verification of existing theories but also insights into interparticle interactions and transition kinetics of bacterial turbulence.
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http://dx.doi.org/10.1126/sciadv.abd1240DOI Listing
April 2021

Synthesis and Biological Activity of Novel Pyrazolo[3,4-d]pyrimidin-4-one Derivatives as Potent Antifungal Agent.

Pest Manag Sci 2021 Apr 9. Epub 2021 Apr 9.

School of Science, Anhui Agricultural University, Hefei, China.

Background: To promote the discovery and development of new fungicide with novel scaffolds or modes of action, a series of novel 5-(2-chloroethyl)-1-phenyl-6-(pyridin-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized, and evaluated for their antifungal activities.

Results: The bioassay data showed that compound 8IIId (EC = 1.93 mg/L) is superior to boscalid (EC = 6.71 mg/L) against Valsa mali. We introduced chiral groups on the structure of 8IIId, and two chiral configurations were respectively synthesized, which are 8Vc and 8Vd. Surprisingly, 8Vc showed significant antifungal activities against Valsa mali and Physalospora piricola with EC values of 0.22 and 0.55 mg/L. Physiological and biochemical studies showed that the primary action mechanism of compound 8Vc on Valsa mali may involve changing mycelial morphology and increasing cell membrane permeability.

Conclusion: These results demonstrated that 8Vc could be further modified as fungicide and provided a valuable reference for antifungal agents with pyrazolo[3,4-d]pyrimidin-4-one skeleton.
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http://dx.doi.org/10.1002/ps.6406DOI Listing
April 2021

Systemic immune-inflammation index predicts postoperative acute kidney injury in hepatocellular carcinoma patients after hepatectomy.

Medicine (Baltimore) 2021 Apr;100(14):e25335

Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.

Abstract: The systemic immune-inflammation index (SII) is an independent prognostic predictor of hepatocellular carcinoma (HCC). The present investigation examined whether an association exists between preoperative SII value and postoperative acute kidney injury (pAKI) in HCC patients.The study included 479 hepatitis B virus (HBV)-associated HCC patients undergoing hepatectomy. The SII was calculated as P × N/L, where P, N, and L represent the counts of platelets, neutrophils, and lymphocytes in routine blood test, respectively. After propensity score matching, logistic regression analysis was used to explore independent predictors of pAKI in HCC patients.pAKI was confirmed in 51 patients (10.8%). The average SII value was higher in patients with pAKI than patients without pAKI. After multivariate logistic regression analysis, SII, history of hypertension, and tumor size, among others, were found to be predictors of pAKI. The optimal threshold value of SII for predicting pAKI was found to be 547.84 × 109/L. Multivariate analysis performed after propensity score matching confirmed that SII ≥ 547.84 × 109/L was an independent predictor of pAKI.The preoperative SII qualifies as a novel, independent predictor of pAKI in HCC patients with HBV infection who underwent hepatectomy.
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http://dx.doi.org/10.1097/MD.0000000000025335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036044PMC
April 2021

A composite risk model predicts disease progression in early stages of COVID-19: A propensity score-matched cohort study.

Ann Clin Biochem 2021 Apr 21:45632211011194. Epub 2021 Apr 21.

Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Recently, studies on COVID-19 have focused on the epidemiology of the disease and clinical characteristics of patients, as well as on the risk factors associated with mortality during hospitalization in critical COVID-19 cases. However, few research has been performed on the prediction of disease progression in particular group of patients in the early stages of COVID-19.

Methods: The study included 338 patients with COVID-19 treated at two hospitals in Wuhan, China, from December 2019 to March 2020. Predictors of the progression of COVID-19 from mild to severe stages were selected by the logistic regression analysis.

Results: COVID-19 progression to severe and critical stages was confirmed in 78 (23.1%) patients. The average value of the neutrophil-to-lymphocyte ratio (NLR) was higher in patients in the disease progression group than in the improvement group. Multivariable logistic regression analysis revealed that elevated NLR, LDH and IL-10 were independent predictors of disease progression. The optimal cut-off value of NLR was 3.75. The values of the area under the curve, reflecting the accuracy of predicting COVID-19 progression by NLR was 0.739 (95%CI: 0.605-0.804). The risk model based on NLR, LDH and IL-10 had the highest area under the ROC curve.

Conclusions: The performed analysis demonstrates that high concentrations of NLR, LDH and IL-10 were independent risk factors for predicting disease progression in patients at the early stage of COVID-19. The risk model combined with NLR, LDH and IL-10 improved the accuracy of the prediction of disease progression in patients in the early stages of COVID-19.
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http://dx.doi.org/10.1177/00045632211011194DOI Listing
April 2021

MIB1 upregulates IQGAP1 and promotes pancreatic cancer progression by inducing ST7 degradation.

Mol Oncol 2021 Apr 1. Epub 2021 Apr 1.

Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Despite recent progress in cancer treatment, the prognosis of patients with pancreatic cancer still remains poor. Pancreatic tumors are reported to display high molecular heterogeneity. Elucidating the molecular mechanisms underlying pancreatic cancer progression is essential for improving patient treatment and survival. The overexpression of E3 ubiquitin ligase mind bomb 1 (MIB1) was previously described in pancreatic cancer cells, where it enhanced tumor cell proliferation. However, the role of MIB1 in pancreatic cancer progression remains elusive. In the present study, we confirmed that MIB1 expression is elevated in pancreatic cancer tissues and that high levels of MIB associate with unfavorable prognosis. Overexpression of MIB1 enhanced proliferation and invasion of pancreatic cancer cells both in vitro and in vivo. We further investigated the molecular mechanisms downstream of MIB1 and observed for the first time that MIB1 targets suppressor of tumorigenicity 7 protein (ST7), previously described as suppressor of tumorigenicity, for proteasomal degradation. Furthermore, we found that ST7 suppressed tumor growth by downregulating IQ motif containing GTPase activating protein 1 (IQGAP1) in pancreatic tumor cells. Thus, these data show that MIB1 promotes pancreatic cancer progression by inducing ST7 degradation followed by downregulation of IQGAP1 in pancreatic cancer cells. In conclusion, our research shows that the MIB1/ST7/IQGAP1 axis is essential for pancreatic cancer progression, and MIB1 inhibition may serve as a novel therapeutic strategy in patients with pancreatic cancer.
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http://dx.doi.org/10.1002/1878-0261.12955DOI Listing
April 2021

High efficiency in-situ biogas upgrading in a bioelectrochemical system with low energy input.

Water Res 2021 Jun 15;197:117055. Epub 2021 Mar 15.

Department of Physical and Biological Sciences, Western New England University, 1215 Wilbraham Rd, Springfield, MA 01119, USA.

Biogas produced from anaerobic digestion usually contains 30%-50% CO much of which must be removed, before utilization. Bioelectrochemical biogas upgrading approaches show promise, however, they have not yet been optimized for practical applications. In this study, a bioelectrochemical system with low energy input (applied cathode potential of -0.5 V vs. standard hydrogen electrode, SHE) was used for in-situ biogas upgrading. High efficiency CO conversion (318.5 mol/d/m) was achieved when the system was operated with an organic load of 1.7 kgCOD/(m d). Methane content in the upgraded biogas was 97.0% and CO concentrations stayed below 3%, which is comparable to biogas upgraded with more expensive and less sustainable physiochemical approaches. The high efficiency of this approach could likely be attributed to a significant enrichment of Methanothrix (92.7%) species on the cathode surface that were expressing genes involved in both acetogenic methanogenesis and direct electron transfer (DET). Electromethanogenesis by these organisms also increased proton consumption and created a higher pH that increased the solubility of CO in the bioreactor. In addition, CO removal from the biogas was likely further enhanced by an enrichment of Actinobacillus species known to be capable of CO fixation. Artificial neural network (ANN) models were also used to estimate CH production under different loading conditions. The ANN architecture with 10 neurons at hidden layers fit best with a mean square error of 6.06 × 10 and R of 0.99.
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http://dx.doi.org/10.1016/j.watres.2021.117055DOI Listing
June 2021

MAL2 interacts with IQGAP1 to promote pancreatic cancer progression by increasing ERK1/2 phosphorylation.

Biochem Biophys Res Commun 2021 May 26;554:63-70. Epub 2021 Mar 26.

Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Pancreatic cancer is a digestive tract malignancy characterized by an occult onset and rapid progression. The genetic heterogeneity of pancreatic cancer is closely related to its highly malignant biological behavior. The myelin and lymphocyte protein 2 (MAL2) is upregulated in multiple cancers at the transcriptional level. However, the exact role of MAL2 in pancreatic cancer remains elusive. In this study, we demonstrated that MAL2 protein and mRNA levels were upregulated in pancreatic cancer. MAL2 overexpression was significantly associated with poor prognosis in patients with pancreatic cancer. We further showed that MAL2 interacted with IQGAP1 to increase ERK1/2 phosphorylation levels, which promoted pancreatic cancer progression. Therefore, these results suggest that MAL2 could be a novel therapeutic target for pancreatic cancer.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.146DOI Listing
May 2021

Neuronal-Plasticity and Reward-Propagation Improved Recurrent Spiking Neural Networks.

Front Neurosci 2021 12;15:654786. Epub 2021 Mar 12.

Research Center for Brain-Inspired Intelligence, Institute of Automation, Chinese Academy of Sciences (CASIA), Beijing, China.

Different types of dynamics and plasticity principles found through natural neural networks have been well-applied on Spiking neural networks (SNNs) because of their biologically-plausible efficient and robust computations compared to their counterpart deep neural networks (DNNs). Here, we further propose a special Neuronal-plasticity and Reward-propagation improved Recurrent SNN (NRR-SNN). The historically-related adaptive threshold with two channels is highlighted as important neuronal plasticity for increasing the neuronal dynamics, and then global labels instead of errors are used as a reward for the paralleling gradient propagation. Besides, a recurrent loop with proper sparseness is designed for robust computation. Higher accuracy and stronger robust computation are achieved on two sequential datasets (i.e., TIDigits and TIMIT datasets), which to some extent, shows the power of the proposed NRR-SNN with biologically-plausible improvements.
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http://dx.doi.org/10.3389/fnins.2021.654786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994752PMC
March 2021

ATP6V0d2 Suppresses Alveoli Macrophage Alternative Polarization and Allergic Asthma via Degradation of PU.1.

Allergy Asthma Immunol Res 2021 May;13(3):479-497

Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan, China.

Purpose: Macrophages are important regulators of environmental allergen-induced airway inflammation and asthma. ATP6V0d2 is a subunit of vacuolar ATPase highly expressed in macrophages. However, the functions of ATP6V0d2 in the regulation of pathogenesis of allergic asthma remain unclear. The aim of this study is to determine the function and related molecular mechanisms of macrophage protein ATP6V0d2 in allergic asthma.

Methods: We compared the disease severity between female C57BL/6 wild-type and mice in an ovalbumin (OVA)-induced asthma model. We also investigated the association of expression of , and with disease severity among asthmatic patients.

Results: The expression of in sputum cells of asthmatic patients and in the lungs of OVA-challenged mice was enhanced compared to healthy subjects and their counterparts, respectively. However, -deficient mice exaggerated inflammatory cell infiltration as well as enhanced alternative activated macrophage (AAM) polarization and mucus production in an OVA-induced asthma model. Furthermore, we found that Atp6v0d2 promoted lysosomal degradation of Pu.1, which induced AAM polarization and Ccl17 production. Among asthma patients, expression was inversely associated with disease severity, whereas and expression was positively associated with disease severity.

Conclusions: Our results identify macrophage Atp6v0d2, as an induced feedback inhibitor of asthma disease severity by promoting Pu.1 lysosomal degradation, which may in turn leads to reduced AAM polarization and Ccl17 production.
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http://dx.doi.org/10.4168/aair.2021.13.3.479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984956PMC
May 2021

Prospective Study on Plasma MicroRNA-4286 and Incident Acute Coronary Syndrome.

J Am Heart Assoc 2021 Mar 10;10(6):e018999. Epub 2021 Mar 10.

Department of Occupational and Environmental Health Key Laboratory of Environment and Health Ministry of Education and State Key Laboratory of Environmental Health (Incubating) School of Public Health Tongji Medical CollegeHuazhong University of Science and Technology Wuhan China.

Background Mounting evidence suggests that circulating microRNAs (miRNAs) are critical indicators of cardiovascular disease. However, prospective studies linking circulating miRNAs to incident acute coronary syndrome (ACS) are limited, and the underlying effect of associated miRNA on incident ACS remains unknown. Methods and Results Based on a 2-stage prospective nested case-control design within the Dongfeng-Tongji cohort, we profiled plasma miRNAs from 23 pairs of incident ACS cases and controls by microarray and validated the candidate miRNAs in 572 incident ACS case-control pairs using quantitative real-time polymerase chain reaction. We observed that plasma miR-4286 was associated with higher risk of ACS (adjusted odds ratio according to an interquartile range increase, 1.26 [95% CI, 1.07-1.48]). Further association analysis revealed that triglyceride was positively associated with plasma miR-4286, and an interquartile range increase in triglyceride was associated with an 11.04% (95% CI, 3.77%-18.83%) increase in plasma miR-4286. In addition, the Mendelian randomization analysis suggested a potential causal effect of triglyceride on plasma miR-4286 ( coefficients: 0.27 [95% CI, 0.01-0.53] and 0.27 [95% CI, 0.07-0.47] separately by inverse variance-weighted and Mendelian randomization-pleiotropy residual sum and outlier tests). Moreover, the causal mediation analysis indicated that plasma miR-4286 explained 5.5% (95% CI, 0.7%-17.0%) of the association of triglyceride with incident ACS. Conclusions Higher level of plasma miR-4286 was associated with an increased risk of ACS. The upregulated miR-4286 in plasma can be attributed to higher triglyceride level and may mediate the effect of triglyceride on incident ACS.
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http://dx.doi.org/10.1161/JAHA.120.018999DOI Listing
March 2021

[Effects of acute high altitude hypoxia on EEG power in different emotional states].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2020 Nov;36(6):556-561

Zhejiang Sci-Tech University, Hangzhou 310018.

To investigate the effects of acute high altitude hypoxia on EEG power in different emotional states. This study was two-factor within-subject design (2 levels of oxygen environment ×4 levels of emotion type). Twelve male subjects aged between 20 and 25 years old were induced to produce four different types of emotions by emotional picture evoked paradigm: low valence and low arousal(LVLA), high valence and low arousal(HVLA), low valence and high arousal(LVHA), high valence and high arousal(HVHA). Brain Products 32 was used to collect EEG signals under different emotional states. The next day, a constant depressed oxygen chamber was used to simulate a 4 300 m plateau hypoxia environment, and the same group of subjects used the same experimental paradigm to collect EEG signals 10h after hypoxia. The collected EEG signals were analyzed by power spectrum (FFT), and the five frequency bands (Delta, Theta, Alpha, beta, gamma) of the frontal lobe (F3\Fz\F4) were analyzed by variance analysis of two-factor repeated measurements. FFT analysis found that before and after acute hypoxia, the whole brain distribution of alpha wave in four emotional states was mainly concentrated in frontal and parietal leaves; the distribution of alpha wave in the whole brain was the least in relaxed emotional state. The results of the two-factor repeated measurement ANOVA showed that: ①the power of delta\ beta band was significantly affected by the oxygen environment(<0.05), and the power was enhanced under hypoxia. ②The power index of theta\ alpha band showed a significant interaction between the oxygen environment and emotional types(<0.05). Except for the HVLA emotional state, the power of theta alpha band was significantly enhanced under hypoxia. ③ The two factors had no significant influence on the gamma band(>0.05). Under the four kinds of emotional states, the difference of the influence of oxygen environment on brain activity was mainly in the frontal lobe, parietal lobe and part of temporal lobe. Of the four types of emotions, the oxygen environment had the least significant effect on brain activity in HVLA emotional states, while the rest showed significant differences.
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http://dx.doi.org/10.12047/j.cjap.5978.2020.117DOI Listing
November 2020

An integrated strategy to enhance performance of anaerobic digestion of waste activated sludge.

Water Res 2021 May 25;195:116977. Epub 2021 Feb 25.

Advanced Water Management Centre, The University of Queensland, St Lucia, QLD 4072, Australia. Electronic address:

Anaerobic digestion (AD) is an essential process in wastewater treatment plants as it can reduce the amount of waste activated sludge (WAS) for disposal, and also enables the recovery of bioenergy (i.e. methane). Here, a new pretreatment method to enhance anaerobic digestion was achieved by treating thickened WAS (TWAS) with ferric (as FeCl) and nitrite simultaneously for 24-hour at room temperature. Biochemical methane potential tests showed markedly improved degradability in the pretreated TWAS, with a relative increase in hydrolysis rate by 30%. A comparative experiment with the operation of two continuous-flow anaerobic digesters further demonstrated the improvement in biogas quantity and quality, digestate disposal, and phosphorus recovery in the experimental digester. The dosed FeCl (i.e. ~6 mM) decreased the pH of TWAS to ~5, which led to the formation of free nitrous acid (FNA, HNO) at parts per million levels (i.e. ~6 mg N/L), after dosing nitrite at 250 mg NO-N/L. This FNA treatment caused a 26% increase in methane yield and volatile solids destruction, 55% reduction in the viscosity of sludge in digester, and 24% less polymer required in further digestate dewatering. In addition, the dosed Fe(III) was reduced to Fe(II) which precipitated sulfide and phosphorus, leading to decreased hydrogen sulfide concentration in biogas, and increased percentage of vivianite in the total crystalline iron species in digested sludge. Our study experimentally demonstrated that combined dosing of FeCl and nitrite is a useful pretreatment strategy for improving anaerobic digestion of WAS.
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http://dx.doi.org/10.1016/j.watres.2021.116977DOI Listing
May 2021

Corrigendum: Dual-Targeting Nanoparticle-Mediated Gene Therapy Strategy for Hepatocellular Carcinoma by Delivering Small Interfering RNA.

Front Bioeng Biotechnol 2021 11;9:656268. Epub 2021 Feb 11.

Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

[This corrects the article DOI: 10.3389/fbioe.2020.00512.].
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http://dx.doi.org/10.3389/fbioe.2021.656268DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906225PMC
February 2021

Phosphate recovery as vivianite using a flow-electrode capacitive desalination (FCDI) and fluidized bed crystallization (FBC) coupled system.

Water Res 2021 Apr 18;194:116939. Epub 2021 Feb 18.

UNSW Water Research Centre, School of Civil and Environmental Engineering, University of New South Wales, Sydney, NSW 2052, Australia; UNSW Centre for Transformational Environmental Technologies, Yixing, Jiangsu Province 214206, P. R. China. Electronic address:

It is critical to both effectively remove and recover phosphate (P) from wastewater given the wide-ranging environmental (i.e., preventing eutrophication and restoring water quality) and economic (i.e., overcoming P resource scarcity) benefits. More recently, considerable academic effort has been devoted towards harvesting P as vivianite, which can be used as a potential slow-release fertilizer and possible reagent for the manufacture of lithium iron phosphate (LiFePO), the precursor in fabricating Li-ion secondary batteries. In this study, we propose an innovative P recovery process, in which P is first preconcentrated via a flow-electrode capacitive deionization (FCDI) device followed by immobilization as vivianite crystals in a fluidized bed crystallization (FBC) column. The effects of different operational parameters on FCDI P preconcentration performance and energy consumption are investigated. Results show that 63% of P can be removed and concentrated in the flow-electrode chamber with a reasonable energy requirement under optimal operating conditions. The FBC system resulted in immobilization of ~80% of P as triangular or quadrangular pellets, which were verified to be high-purity vivianite crystals by scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDX) and extended X-ray absorption fine structure (EXAFS) spectroscopy. This study provides a pathway for efficient recovery of P as a value-added product (i.e., vivianite) from P-rich wastewaters.
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http://dx.doi.org/10.1016/j.watres.2021.116939DOI Listing
April 2021

Hessian-MRLoG: Hessian information and multi-scale reverse LoG filter for pulmonary nodule detection.

Comput Biol Med 2021 Apr 16;131:104272. Epub 2021 Feb 16.

Computer Department, Jingdezhen Ceramic Institute, Jingdezhen, 333403, China.

Computer-aided detection (CADe) of pulmonary nodules is an effective approach for early detection of lung cancer. However, due to the low contrast of lung computed tomography (CT) images, the interference of blood vessels and classifications, CADe has the problems of low detection rate and high false-positive rate (FPR). To solve these problems, a novel method using Hessian information and multi-scale reverse Laplacian of Gaussian (LoG) (Hessian-MRLoG) is proposed and developed in this work. Also, since the intensity distribution of the LoG operator and the lung nodule in CT images are inconsistent, and their shapes are mismatched, a multi-scale reverse Laplacian of Gaussian (MRLoG) is constructed. In addition, in order to enhance the effectiveness of target detection, the second-order partial derivatives of MRLoG are partially adjusted by introducing an adjustment factor. On this basis, the Hessian-MRLoG model is developed, and a novel elliptic filter is designed. Ultimately, in this study, the method of Hessian-MRLoG filtering is proposed and developed for pulmonary nodule detection. To verify its effectiveness and accuracy, the proposed method was used to analyze the LUNA16 dataset. The experimental results revealed that the proposed method had an accuracy of 93.6% and produced 1.0 false positives per scan (FPs/scan), indicating that the proposed method can improve the detection rate and significantly reduce the FPR. Therefore, the proposed method has the potential for application in the detection, localization and labeling of other lesion areas.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104272DOI Listing
April 2021

Inhibition of fibroblast IL-6 production by ACKR4 deletion alleviates cardiac remodeling after myocardial infarction.

Biochem Biophys Res Commun 2021 Apr 18;547:139-147. Epub 2021 Feb 18.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China; Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Fibrotic scarring is tightly linked to the development of heart failure in patients with post-myocardial infarction (MI). Atypical chemokine receptor 4 (ACKR4) can eliminate chemokines, such as C-C chemokine ligand 21 (CCL21), which is independently associated with heart failure mortality. However, the role of ACKR4 in the heart during MI is unrevealed. This study aimed to determine whether ACKR4 modulates cardiac remodeling following MI and to illuminate the potential molecular mechanisms. The expression of ACKR4 was upregulated in the border/infarct area, and ACKR4 was predominantly expressed in cardiac fibroblasts (CFs). Knockout of ACKR4 protected against adverse ventricular remodeling in mice post-MI. These protective effects of ACKR4 deficiency were independent of dendritic cell immune response but could be attributed to downregulated CF-derived IL-6, affecting CF proliferation and endothelial cell (EC) functions, which consequently inhibited cardiac fibrosis. ACKR4 promoted IL-6 generation and proliferation of CFs. Besides, ACKR4 induced endothelial-to-mesenchymal transition (EndMT) in ECs through IL-6 paracrine effect. The p38 MAPK/NF-κB signaling pathway was involved in ACKR4 facilitated IL-6 generation. Moreover, ACKR4 overexpression in vivo via AAV9 carrying a periostin promoter aggravated heart functional impairment post-MI, which was abolished by IL-6 neutralizing antibody. Therefore, our study established a novel link between ACKR4 and IL-6 post-MI, indicating that ACKR4 may be a novel therapeutic target to ameliorate cardiac remodeling.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.013DOI Listing
April 2021

Sequential Sonogashira/intramolecular aminopalladation/cross-coupling of -ethynyl-anilines catalyzed by a single palladium source: rapid access to 2,3-diarylindoles.

Org Biomol Chem 2021 Feb;19(6):1329-1333

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.

We have developed a practical and efficient one-pot protocol for the synthesis of 2,3-diarylindoles via Pd-catalyzed bis-arylative cyclization of various o-ethynylanilines with aryl iodides. Mechanism studies showed that a Pd-catalyzed Sonogashira reaction took place firstly, giving an internal alkyne intermediate, which subsequently underwent intramolecular aminopalladation/cross-coupling to give access to 2,3-diarylindoles. The present methodology exhibits a broad substrate scope, producing various 2,3-diaryl indoles bearing two different aryl groups.
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http://dx.doi.org/10.1039/d0ob02295kDOI Listing
February 2021

SNP rs2243828 in MPO associated with myeloperoxidase level and atrial fibrillation risk in Chinese Han population.

J Cell Mol Med 2020 09 16;24(17):10263-10266. Epub 2020 Jul 16.

Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research and Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China.

Previous studies shown that myeloperoxidase (MPO) level is higher in patients with atrial fibrillation (AF); however, no genetic evidence between MPO and AF risk in human population was observed. Therefore, the present study was aimed to investigate the association between rs2243828, a variant in promoter region of MPO and the risk of AF in Chinese GeneID population. The results demonstrated that the minor G allele of rs2243828 showed a significant association with AF in two independent population (GeneID-north population with 694 AF cases and 710 controls, adjusted P = 6.25 × 10 with an odds ratio was 0.77, GeneID-central population with 1106 cases and 1501 controls, P = 9.88 × 10 with an odds ratio was 0.75). The results also showed G allele was significantly associated with lower plasma concentration of myeloperoxidase in general population. We also observed a significant difference of odds ratio between subgroups of hypertension and non-hypertension. Therefore, our findings identified variant in MPO associated with risk of AF and it may give strong evidence to link the inflammation with the incidence of AF.
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http://dx.doi.org/10.1111/jcmm.15644DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520285PMC
September 2020

Loss of Wip1 aggravates brain injury after ischaemia/reperfusion by overactivating microglia.

Stroke Vasc Neurol 2021 Jan 15. Epub 2021 Jan 15.

Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China.

Background And Purpose: The inflammatory response mediated by microglia/macrophages is closely related to cerebral ischaemia/reperfusion injury. Wild-type p53-induced protein phosphatase 1 (Wip1), a serine/threonine phosphatase, is expressed in various tissues. A growing number of reports have suggested that Wip1 is a negative regulator of inflammation in peripheral tissue; however, its role in the central nervous system (CNS) remains unclear. This study aimed to clarify whether Wip1 can inhibit CNS inflammation by regulating microglia/macrophage functions after ischaemic injury.

Methods: A model of middle cerebral artery occlusion and reperfusion was established in mice. CNS inflammation was simulated by lipopolysaccharide treatment of primary microglia. Laser speckle imaging was used to monitor regional cerebral blood flow. Behavioural outcomes were assessed with a TreadScan gait analysis system. TTC staining was used to evaluate the infarct volume, and western blotting and immunofluorescence staining were applied to detect the phenotypical transformation of microglia. ELISA was performed to detect the levels of inflammatory factors.

Results: Wip1 expression was increased after ischaemia/reperfusion. Wip1-knockout (KO) mice displayed more severe brain injury than wild-type mice, as indicated by aggravated motor dysfunction, greater brain infarct volumes and higher expression of inflammatory cytokines (interleukin-6 and tumour necrosis factor alpha) in the brain. We also found that Wip1 depletion increased microglial/macrophage activation in both in vitro and in vivo models, which all showed activation of microglia/macrophages. Lentivirus- reversed the injury induced by Wip1-KO.

Conclusions: Our results suggest that Wip1 may inhibit neuroinflammation by inhibiting microglial/macrophage activation after brain ischaemia/reperfusion injury.
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http://dx.doi.org/10.1136/svn-2020-000490DOI Listing
January 2021

Ion-exchange enabled synthetic swarm.

Nat Nanotechnol 2021 03 11;16(3):288-295. Epub 2021 Jan 11.

Department of Chemistry, The University of Hong Kong, Hong Kong, China.

Active matters are out-of-equilibrium systems that convert energy from the environment to mechanical motion. Non-reciprocal interaction between active matters may lead to collective intelligence beyond the capability of individuals. In nature, such emergent behaviours are ubiquitously observed in animal colonies, giving these species remarkable adaptive capability. In artificial systems, however, the emergence of non-trivial collective intelligent dynamics remains undiscovered. Here we show that a simple ion-exchange reaction can couple self-propelled ZnO nanorods and sulfonated polystyrene microbeads together. Chemical communication is established that enhances the reactivity and motion of both nanorods and the microbeads, resulting in the formation of an active swarm of nanorod-microbead complexes. We demonstrate that the swarm is capable of macroscopic phase segregation and intelligent consensus decision-making.
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http://dx.doi.org/10.1038/s41565-020-00825-9DOI Listing
March 2021

Expression and function of Ndel1 during the differentiation of neural stem cells induced by hippocampal exosomesticle.

Stem Cell Res Ther 2021 Jan 9;12(1):51. Epub 2021 Jan 9.

Department of Human Anatomy, Institute of Neurobiology, Medical School of Nantong University, No. 19 Qixiu Road, No. 3 Building of Qixiu Campus, Nantong, 226001, Jiangsu, China.

Background: In the brain of adult mammals, neural stem cells persist in the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus, which are specialized niches with proliferative capacity. Most neural stem cells are in a quiescent state, but in response to extrinsic stimuli, they can exit from quiescence and become reactivated to produce new neurons, so neural stem cells are considered to be a potential source for cell replacement therapy of many nervous system diseases. We characterized the expression of Ndel1 during the differentiation of neural stem cells induced by hippocampus exosomes, and assessed the effect of Ndel1 on neural stem cells differentiation.

Methods: Hippocampal exosomes were isolated and extracted, and co-cultured exosomes with neural stem cells. Western blot, flow cytometry, and immunofluorescence analyses were used to analyze expression of neuronal markers. Further, utilizing high-throughput RNA sequencing technology, we found that nudE neurodevelopment protein 1-like 1 was significantly upregulated in exosomes derived from denervated hippocampus, and then characterized its mechanism and function during neural stem cells differentiation by qRT-PCR, western blot, flow cytometry, and immunofluorescence analyses.

Results: Our results revealed that exosomes of denervated hippocampus promoted the differentiation of neural stem cells into neuron. Hence, we identified that nudE neurodevelopment protein 1-like 1 was significantly upregulated and highly expressed in the nervous system. In addition, we found that miR-107-3p may regulate neural stem cell differentiation by targeting Ndel1.

Conclusions: Our results revealed that deafferentation of the hippocampal exosomes co-cultured with neural stem cells could promote them to differentiate into neurons. Hence, we found that miR-107-3p may regulate neural stem cells differentiation by targeting Ndel1. Importantly, Ndel1 enhanced spatial learning and hippocampal neurogenesis in rats after fimbria fornix transection in vivo. These findings set the stage for a better understanding of neurogenesis, a process that 1 day may inspire new treatments for central nervous system diseases.
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http://dx.doi.org/10.1186/s13287-020-02119-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796549PMC
January 2021

Identification and Verification of Immune-Related Gene Prognostic Signature Based on ssGSEA for Osteosarcoma.

Front Oncol 2020 15;10:607622. Epub 2020 Dec 15.

Department of Orthopedics, Second Xiangya Hospital, Central South University, Changsha, China.

Osteosarcoma is the most common malignant bone tumor in children and adolescence. Multiple immune-related genes have been reported in different cancers. The aim is to identify an immune-related gene signature for the prospective evaluation of prognosis for osteosarcoma patients. In this study, we evaluated the infiltration of immune cells in 101 osteosarcoma patients downloaded from TARGET using the ssGSEA to the RNA-sequencing of these patients, thus, high immune cell infiltration cluster, middle immune cell infiltration cluster and low immune cell infiltration cluster were generated. On the foundation of high immune cell infiltration cluster vs. low immune cell infiltration cluster and normal vs. osteosarcoma, we found 108 common differentially expressed genes which were sequentially submitted to univariate Cox and LASSO regression analysis. Furthermore, GSEA indicated some pathways with notable enrichment in the high- and low-immune cell infiltration cluster that may be helpful in understanding the potential mechanisms. Finally, we identified seven immune-related genes as prognostic signature for osteosarcoma. Kaplan-Meier analysis, ROC curve, univariate and multivariate Cox regression further confirmed that the seven immune-related genes signature was an innovative and significant prognostic factor independent of clinical features. These results of this study offer a means to predict the prognosis and survival of osteosarcoma patients with uncovered seven-gene signature as potential biomarkers.
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http://dx.doi.org/10.3389/fonc.2020.607622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771722PMC
December 2020

Hypoxia Augments Cerebral Inflammation in a Dextran Sulfate Sodium-Induced Colitis Mouse Model.

Front Cell Neurosci 2020 9;14:611764. Epub 2020 Dec 9.

Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing, China.

The importance of hypoxia in the pathophysiology of inflammatory bowel disease (IBD) is increasingly being realized; also, hypoxia seems to be an important accelerator of brain inflammation, as has been reported by our group and others. IBD is a chronic intestinal disorder that leads to the development of inflammation, which is related to brain dysfunction. However, no studies have reported whether hypoxia is associated with IBD-induced neuroinflammation. Therefore, the objective of the present study was to determine whether hypoxia augments cerebral inflammation in a DSS-induced colitis mouse model. The mouse model was developed using 3% DSS for five days combined with exposure to hypoxic conditions (6,000 m) for two days. Mice were randomly divided into four groups: control group, DSS group, hypoxia group, and DSS plus hypoxia group. The results demonstrated that DSS combined with hypoxia resulted in up-regulation of colonic and plasmatic proinflammatory cytokines. Meanwhile, DSS plus hypoxia increased expression of Iba1, which is a marker of activated microglia, accompanied by increased expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in the brain. Moreover, the expression of tight junction proteins, such as zonula occludens-1 (ZO-1), occludin, and claudin-5, was markedly downregulated. The current study provides new insight into how hypoxia exposure induces excessive inflammatory responses andpathophysiological consequences in the brain in a DSS-induced colitis model.
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http://dx.doi.org/10.3389/fncel.2020.611764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756107PMC
December 2020

The role of hippocampus niche exosomes in rat hippocampal neurogenesis after fimbria-fornix transection.

J Biol Chem 2020 Dec 17. Epub 2020 Dec 17.

The Jiangsu Key Laboratory of Neuroregeneration, The Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Co-innovation Center of Neuroregeneration, China.

Exosomes transfer signaling molecules such as proteins, lipids and RNAs to facilitate cell-cell communication and play an important role in the stem cell microenvironment. In previous work we demonstrated that rat fimbria-fornix transection (FFT) enhances neurogenesis from neural stem cells (NSCs) in the subgranular zone (SGZ). However, how neurogenesis is modulated after denervation remains unknown. Here, we investigated whether exosomes in a denervated hippocampal niche may affect neurogenesis. Using the FFT rat model, we extracted hippocampal exosomes and identified them using Western blots, transmission electron microscopy (TEM) and nanoparticle size measurement. We also used RNA sequencing and bioinformatic analysis of exosomes to identify noncoding RNA expression profiles and neurogenesis-related miRNAs, respectively. RNA sequencing analysis demonstrated 9 upregulated and 15 downregulated miRNAs. miR-3559-3P and miR-6324 increased gradually after FFT. Thus, we investigated the function of miR-3559-3P and miR-6324 with NSC proliferation and differentiation assays. Transfection of miR-3559-3p and miR-6324 mimics inhibited the proliferation of NSCs and promoted the differentiation of NSCs into neurons, while miR-3559-3p and miR-6324 inhibitors promoted NSC proliferation and inhibited neuronal differentiation. Additionally, the exosome marker molecules CD9, CD63, and Alix were expressed in exosomes extracted from the hippocampal niche. Finally, TEM showed that exosomes were ~100 nm in diameter and had a "saucer-like" bilayer membrane structure. Taken together, these findings suggest that differentially expressed exosomes and their related miRNAs in the denervated hippocampal niche can promote differentiation of NSCs into neurons.
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http://dx.doi.org/10.1074/jbc.RA120.015561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7948408PMC
December 2020

The application possibility of acellular dermal matrix decorated with nano-silver in the reconstruction of contaminated abdominal wall.

Mater Sci Eng C Mater Biol Appl 2021 Feb 17;119:111645. Epub 2020 Oct 17.

Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China. Electronic address:

Acellular dermal matrix (ADM) is a biomaterial, which commonly used for repair of tissue defects; however, infection is the main factor underlying the failure of treatments involving ADM. To enhance the anti-infection ability of ADM, we constructed a new form of ADM that was decorated with nano-silver ('NS-ADM'). The introduction of nano-silver did not destroy the decellularized structure of ADM, and no significant difference was detected with regards to the maximum tensile force when compared between NS-ADM and ADM (P = 0.351). NS-ADM was not cytotoxic to cell growth when the concentration of nano-silver solution ≤ 25 ppm and exhibited strong antibacterial activity in vitro. Besides, when rats were inoculated with 10 CFU/mL, there were significantly lower bacterial counts in the NS-ADM group than in the ADM group when assessed seven days after surgery (P = 0.047); no significant differences were detected on days 14 and 28. Although there were no significant differences in bacterial counts on days 7, 14, or 21 between the two groups (rats were inoculated with 10 CFU/mL), the number of rats showing reduced bacterial counts or clearing was higher in the NS-ADM group than in the ADM group. Rats that were inoculated with 10 CFU/mL showed repair failure. Overall, NS-ADM is a promising antibacterial biomaterial for repairing contaminated soft-tissue defects, in which antibacterial properties are superior to ADM. The antibacterial activity of NS-ADM was limited for severe infections, and further in vivo studies are needed to evaluate its efficacy and biosafety.
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http://dx.doi.org/10.1016/j.msec.2020.111645DOI Listing
February 2021

Close Homolog of L1 Deficiency Exacerbated Intestinal Epithelial Barrier Function in Mouse Model of Dextran Sulfate Sodium-Induced Colitis.

Front Physiol 2020 6;11:584508. Epub 2020 Nov 6.

Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing, China.

The cell adhesion molecule CHL1, which belongs to the immunoglobulin superfamily, functions in a variety of physiological and pathological processes, including neural development, tissue injury, and repair. We previously found that the loss of CHL1 exacerbated the dextran sulfate sodium (DSS)-induced colitis in mice. In the present study, we further addressed the role of CHL1 in mouse model of DSS-induced colitis and its' potential mechanism. Colon tissues were collected from CHL1, CHL1, and CHL1 mice after DSS induction to investigate the effects of CHL1 on the development of colitis. The data showed that CHL1 was expressed in intestine tissue, and expression of CHL1 was increased by DSS-induced inflammation. CHL1 deficiency induced more pronounced colitis features, exacerbated inflammation, and damage to colonic tissues in DSS-induced mice. Moreover, colonic tissues of CHL1 mice showed a marked increase in neutrophil and macrophage infiltration, be accompanied by more severe damage to intestinal epithelial cells and higher fluorescein isothiocyanate (FITC) leakage. Our results revealed deficiency of CHL1 exacerbated DSS-induced colitis, and this pathogenesis was potentially mediated by disruption of intestinal barrier integrity, indicating that CHL1 may be an attractive therapeutic target for inflammatory bowel diseases (IBDs) in mice.
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http://dx.doi.org/10.3389/fphys.2020.584508DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677258PMC
November 2020

DGAT1 protects tumor from lipotoxicity, emerging as a promising metabolic target for cancer therapy.

Mol Cell Oncol 2020 Sep 8;7(6):1805257. Epub 2020 Sep 8.

Department of Radiation Oncology, James Comprehensive Cancer Center and College of Medicine at the Ohio State University, Columbus, OH, USA.

We recently demonstrated that glioblastoma, the most lethal brain cancer, upregulates diacylglycerol O-acyltransferase 1 (DGAT1) to store excess fatty acids into triglycerides to prevent lipotoxicity and promote tumor growth. Targeting DGAT1 resulted in marked tumor cell death by triggering extensive oxidative stress, indicating that DGAT1 could be a promising target for cancer therapy.
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http://dx.doi.org/10.1080/23723556.2020.1805257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671038PMC
September 2020