Publications by authors named "Dandan Zhang"

610 Publications

Utilization of Spent FCC Catalyst as Fine Aggregate in Non-sintered Brick: Alkali Activation and Environmental Risk Assessment.

Front Chem 2021 26;9:674271. Epub 2021 Apr 26.

State Key Laboratory of Safety and Control for Chemicals, SINOPEC Research Institute of Safety Engineering, Qingdao, China.

This study focuses on the recycling of a spent fluid catalytic cracking (FCC) catalyst to produce catalyst-based non-sintered bricks (CN-bricks) for the recovery of its aluminosilicate components and the solidification of heavy metals. The effects of the content of cement (10-20%), the proportion of FCC (10-40%), and the type of an activator (NaOH/NaSiO/NaSO) on the performance of a CN-brick were investigated in terms of the mechanical strength and leaching behavior. The results show that an optimal binder system of 20% cement + NaSO could promote the compressive strength up to 42.3 MPa; the proportion of an optimal spent FCC catalyst of 20% could achieve the lowest porosity and water absorption. The microscopic mechanism of a cementitious process was analyzed by x-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM), proving that C-S-H and ettringite (AFt) are the two main hydration products of a CN-brick. NaSO is superior to NaOH or NaSiO as an activator since NaSO takes advantage of the aluminum-rich property of a spent FCC catalyst and specifically promote the formation of a needle-like AFt. Quantitative environmental risk assessment for the utilization of a CN-brick on roads was carried out based on the leaching test of a toxicity characteristic leaching procedure (TCLP), NEN 7371 maximum availability test, and the hazard Index (HI) identification, and a final HI 0.0045 (<1.0) indicates an acceptable risk for environment and nearby residents as CN-bricks are utilized on roads for 30 years.
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http://dx.doi.org/10.3389/fchem.2021.674271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108481PMC
April 2021

Synthesis of Oxygen-Rich Bismuth Oxybromide (BiOBr) Photocatalyst for High Efficiency Degradation of Sulfadiazine Under Simulated Sunlight.

J Nanosci Nanotechnol 2021 Nov;21(11):5477-5485

School of Materials Science and Engineering, Hebei University of Engineering, Handan 056038, p. R. China.

At present, compared with other antibiotic degradation systems, there are few literatures on pho- tocatalytic degradation of sulfadiazine (SDZ). In this research, it was firstly discovered that the oxygen-rich bismuth oxybromide (BiO Br) photocatalyst can efficiently degrade SDZ under simulated sunlight. In this paper, the prepared BiOBr photocatalyst by mixed solvothermal method represented outstanding photocatalytic performance. The catalyst synthesized at 120 °C and pH = 10 showed optimum degradation function in the samples prepared at various temperatures and pH value. After 3 h of irradiation, 96.2% of SDZ solution could be decomposed. The effects of preparation conditions, catalyst dosage, initial SDZ concentration and initial SDZ pH value on photocatalytic degradation efficiency were investigated systematically. Besides, the effect of active species was studied by trapping tests, and it was concluded that 'O₂ contributes the most to the photocatalytic process. A possible photocatalytic degradation mechanism was proposed.
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http://dx.doi.org/10.1166/jnn.2021.19479DOI Listing
November 2021

Arbutin inhibits inflammation and apoptosis by enhancing autophagy via SIRT1.

Adv Clin Exp Med 2021 May 11. Epub 2021 May 11.

Department of Ophthalmology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, China.

Background: SIRT1 plays a protective role against diabetic retinopathy as it regulates inflammation, apoptosis and autophagy of cells.

Objectives: This study was designed to investigate the effects of arbutin and to identify a potential mechanism of action. Adult human retinal pigment epithelial (ARPE-19) cells were exposed to high glucose (HG) or treated with different concentrations of arbutin.

Material And Methods: The protein levels of pro-inflammatory cytokines, like tumor necrosis factor-α (TNF-α), interleukin (IL)-1β), IL-6, and p65 were assessed using enzyme-linked immunosorbent assay (ELISA). The expression of NF-κB p65 and cyclooxygenase-2 (COX-2) was detected with western blot assay. Cell apoptosis was analyzed with TUNEL assay, and expression levels of Bcl2, BAX, cleaved caspase-3, cleaved PARP, LC3II, LC3I, and beclin1 were detected with western blot assay. Autophagy levels were detected using LC3II immunofluorescence staining.

Results: Arbutin treatment markedly enhanced viability and autophagy mediators, decreased pro-inflammatory proteins and reduced apoptosis in ARPE cells under HG exposure, while increasing SIRT1 protein level. This could be blocked by Sirtinol treatment. Additionally, 3MA treatment significantly reduced the efficacy of arbutin against inflammatory markers and apoptosis in ARPE cells exposed to HG.

Conclusions: Arbutin suppressed inflammation and apoptosis of ARPE cells induced by HG by promoting autophagy via SIRT1. A potential target, SIRT1, was identified for the treatment of DR, and new effects of and action mechanisms for arbutin were found and confirmed.
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http://dx.doi.org/10.17219/acem/133493DOI Listing
May 2021

Efficacy and Safety of (Xueshuantong) in Patients With Acute Ischemic Stroke (EXPECT) Trial: Rationale and Design.

Front Pharmacol 2021 22;12:648921. Epub 2021 Apr 22.

Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, China.

Although revascularization treatment is recommended as the first-line therapy for patients with non-minor acute ischemic stroke (AIS), it only benefits a minority of patients. Previous studies have reported the positive effects of (PNS) (Xueshuantong lyophilized powder) on AIS, however, there have been no rigorous trials. This study aims to assess the efficacy and safety of PNS therapy for patients with AIS. The Evaluation of Xueshuantong in Patients with acutE ischemiC sTroke (EXPECT) trial is a multicenter, randomized, placebo-controlled, double-blind study aiming to enroll 480 patients in China. Eligible patients with AIS within 72 h of symptom onset will randomly receive either PNS or PNS placebo for 10 days and subsequently be followed up to 90 days. The primary outcome will be a change in the National Institute of Health Stroke Scale (NIHSS) score from baseline to 10 post-randomization days. The secondary outcomes include early neurological improvement (proportion of patients with NIHSS score 0-1), and Patient-Reported Outcomes Scale for Stroke score at 10 post-randomization days, the proportion of patients with life independence (modified Rankin Scale score of 0-1), the proportion of patients with a favorable outcome (Barthel Index ≥90), and Stroke-Specific Quality of Life score at 90 days. Adverse events or clinically significant changes in vital signs and laboratory parameters, regardless of the severity, will be recorded during the trial to assess the safety of PNS. To our knowledge, this study is the first double-blind trial to assess the efficacy and safety of PNS in patients with AIS. Findings of the EXPECT trial will be valuable in improving evidence regarding the clinical application of PNS therapy in patients with AIS ineligible for revascularization treatment in the reperfusion era.
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http://dx.doi.org/10.3389/fphar.2021.648921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101545PMC
April 2021

Association of angiotensin-converting enzyme gene insertion/deletion polymorphism and obstructive sleep apnoea in a Chinese population: A meta-analysis.

J Renin Angiotensin Aldosterone Syst 2020 Apr-Jun;21(2):1470320320934716. Epub 2020 Jun 17.

Department of Respiratory and Critical Care Medicine, ShenZhen Hospital of Southern Medical University, PR China.

Introduction: Many studies have investigated the association between angiotensin-converting enzyme () gene insertion/deletion (I/D) polymorphism and susceptibility to obstructive sleep apnoea (OSA). However, few have confirmed the relationship between ACE and OSA in the Chinese population. We performed a meta-analysis of studies relating the I/D polymorphism to the risk of OSA in a Chinese population.

Methods: We evaluated eligible published studies from several databases for this meta-analysis. Subgroup analyses were performed for hypertension. Pooled odds ratios and 95% confidence intervals were calculated using a fixed- or random-effects model.

Results: Ten studies were identified to analyse the association between I/D polymorphism and OSA risk. No marked associations were found in any genetic model (>0.05). Subgroup analysis showed an association with hypertension (D vs. I, DD vs. II, ID vs. DD+II, DD+ID vs. II, ID vs. II; <0.05), which was confirmed by sensitivity analyses. No obvious publication bias was found using Egger's test (>0.05).

Conclusions: The I/D polymorphism was not associated with an increased risk of OSA in a Chinese population. However, within the hypertensive subgroup, we detected a significant association between the polymorphism and OSA. More case-control investigations are required.
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http://dx.doi.org/10.1177/1470320320934716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301659PMC
June 2020

Azilsartan ameliorates ox-LDL-induced endothelial dysfunction via promoting the expression of KLF2.

Aging (Albany NY) 2021 May 4;13. Epub 2021 May 4.

Department of Cardiology, Ganzhou People’s Hospital, Ganzhou 341000, Jiangxi, China.

Background: Oxidized LDL(Ox-LDL) mediated endothelial dysfunction is involved in the pathogenesis of various cardiovascular diseases, including atherosclerosis. Azilsartan is a potent agent for the treatment of hypertension as the antagonist of the angiotensin II receptor. This study will investigate whether Azilsartan possesses a beneficial effect against endothelial cell dysfunction induced by ox-LDL and explore the underlying preliminary mechanism.

Methods: Ox-LDL was applied to construct an endothelial dysfunction model in human umbilical vascular endothelial cells (HUVECs). The expression of lectin-type oxidized LDL receptor 1 (LOX-1), endothelial nitric oxide synthase (eNOS), tight junction protein occludin, and transcriptional factor Krüppel-like factor 2 (KLF2) was detected using qRT-PCR and Western blot. ELISA and qRT-PCR were utilized to evaluate the production of chemokine monocyte chemotactic protein 1 (MCP-1) and chemokine (C-X-C motif) Ligand 1 Protein (CXCL1) in treated HUVECs. The generation of nitro oxide (NO) was determined using DAF-FM DA staining assay. KLF2 was silenced by transfecting the cells with specific Small interfering RNA (siRNA). FITC-dextran permeation assay was used to check the endothelial monolayer permeability of treated HUVECs.

Results: Firstly, the elevated expressions of LOX-1, MCP-1, and CXCL-1 induced by stimulation with ox-LDL were significantly suppressed by Azilsartan. The downregulated eNOS and reduced production of NO induced by ox-LDL were reversed by the introduction of Azilsartan. Secondly, enlarged endothelial monolayer permeability and decreased expression of occludin stimulated with ox-LDL were greatly reversed by treatment with Azilsartan but were abolished by silencing the expression of KLF2. Lastly, the inhibited expression of KLF2 induced by ox-LDL was significantly elevated by the introduction of Azilsartan.

Conclusion: Azilsartan might ameliorate ox-LDL-induced endothelial damage via elevating the expression of KLF2.
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http://dx.doi.org/10.18632/aging.202973DOI Listing
May 2021

Myelin regulatory factor deficiency is associated with the retinal photoreceptor defects in mice.

Vis Neurosci 2021 May 3;38:E005. Epub 2021 May 3.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

Previously, we reported the myelin regulatory factor (MYRF) as a candidate gene for nanophthalmos. We have also produced Myrf knockdown (Myrf+/-) mouse strain to investigate the cellular and molecular phenotypes of reduced MYRF expression in the retina. Myrf+/- mouse strain was generated using the CRISPR/Cas9 system. Optomotor response system, electroretinogram (ERG), spectral-domain optical coherence tomography (SD-OCT), histology, and immunohistochemistry were performed to evaluate retinal spatial vision, electrophysiological function, retinal thickness, and pathological changes in cone or rod photoreceptors, respectively. RNA sequencing (RNA-seq) was performed to investigate the underlying molecular mechanism linking Myrf deficiency with photoreceptor defects. The genotype and phenotype of CRISPR/Cas9-induced Myrf+/- mice and their offspring were comprehensively investigated. Photoreceptor defects were detected in the retinas of Myrf+/- mice. Visual acuity and ERG responses were decreased in Myrf+/- mice compared with the control mice (Myrf+/+). The loss of cone and rod neurons was proportional to the decreased outer nuclear layer (ONL) thickness. Moreover, RNA-seq revealed that phototransduction and estrogen signaling pathways played important roles in the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Myrf+/- mouse strain provides a good model to investigate the function of the MYRF gene. Photoreceptor defects with impaired functions of spatial vision and retinal electrophysiology indicate an important role played by MYRF in retinal development. Alterations in phototransduction and estrogen signaling pathways play important roles in linking Myrf deficiency with retinal photoreceptor defects.
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http://dx.doi.org/10.1017/S0952523821000043DOI Listing
May 2021

The effect of introducing Ga on the ZSM-5-catalyzed methanol to aromatics reaction: taking methylcyclopentane to benzene as an example.

Phys Chem Chem Phys 2021 May 30;23(18):10988-11003. Epub 2021 Apr 30.

Key Laboratory of Coal Science and Technology of Ministry of Education and Shanxi Province, Taiyuan University of Technology, No. 79 Yingze West Street, Taiyuan 030024, Shanxi, P. R. China.

Naphthenes are key intermediates in the formation of aromatic compounds during the methanol to aromatics (MTA) reaction, and the dehydrogenation process is more important than the hydrogen transfer process. Theoretical studies were performed to investigate the methylcyclopentane, which represents a naphthene, to benzene MTA process catalyzed by ZSM-5 before and after introducing Ga, showing that Ga-ZSM-5 was more favorable for carrying out the reaction than two H-type ZSM-5 (H-Z and H-Z) models. H-Z and H-Z are favorable for the transfer of H during ring expansion reactions and the reformation of Brønsted acids, but the dehydrogenation reactions involving H-Z and H-Z require high free-energy barriers to be overcome. Although introducing Ga to ZSM-5 is not conducive to the transfer of H after dehydrogenation, it can reduce the extremely high dehydrogenation free-energy barrier compared with H-Z and H-Z; this is mainly because Ga at dehydrogenation active centers, [GaH], can accept electrons and donate them to the H atoms of [GaH], giving H negative charge and making it easy to combine with positive B-acid H atoms that come from methylcyclopentane, cyclohexene, and cyclohexadiene to produce H. Also, analysis of the transition state structures of all DH processes shows that Ga-ZSM-5 is more favorable for promoting the combination of H to produce H than H-Z and H-Z.
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http://dx.doi.org/10.1039/d0cp05778aDOI Listing
May 2021

The Influence Mechanism of Temperature and Storage Period on Polarization Properties of Poly (Vinylidene Fluoride-Trifluoroethylene) Ultrathin Films.

Membranes (Basel) 2021 Apr 21;11(5). Epub 2021 Apr 21.

School of Mathematics, Physics and Statistics, Shanghai University of Engineering Science, Shanghai 201620, China.

The effect of testing temperature and storage period on the polarization fatigue properties of poly (vinylidene fluoride-trifluoroethylene) (P(VDF-TrFE)) ultrathin film devices were investigated. The experimental results show that, even after stored in air for 150 days, the relative remanent polarization (Pr/Pr(0)) of P(VDF-TrFE) of ultrathin films can keep at a relatively high level of 0.80 at 25 °C and 0.70 at 60 °C. To account for this result, a hydrogen fluoride (HF) formation inhibition mechanism was proposed, which correlated the testing temperature and the storage period with the microstructure of P(VDF-TrFE) molecular chain. Moreover, a theoretical model was constructed to describe the polarization fatigue evolution of P(VDF-TrFE) samples.
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http://dx.doi.org/10.3390/membranes11050301DOI Listing
April 2021

Anterior vitrectomy, phacoemulsification cataract extraction and irido-zonulo-hyaloid-vitrectomy in protracted acute angle closure crisis.

Int Ophthalmol 2021 Apr 27. Epub 2021 Apr 27.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, China.

Purpose: To describe a modified surgical approach with anterior vitrectomy, phacoemulsification (phaco) cataract extraction and irido-zonulo-hyaloid-vitrectomy (IZHV) in protracted acute angle closure crisis (AACC).

Patients And Methods: Non-comparative, retrospective case series including 21 eyes in 19 consecutive cases of protracted AACC, which persists for at least 7 days despite maximal medical and laser therapies, were included in this study. All patients underwent a modified surgical procedure with anterior vitrectomy, phaco cataract extraction, IOL implantation, goniosynechialysis (GSL) and IZHV, using modest phaco dynamic parameters with intraocular pressure (IOP) set at 30 mmHg through the procedure using Centurion® Vision System equipped with active fluidics while the anterior vitrectomy was set at 4000 or 5000 rpm. IOP and anterior chamber space were maintained through the procedure using ophthalmic viscosurgical device (OVD) injected through paracentesis whenever the Phaco or I/A probe was withdrawn from within the anterior chamber. Medical history, visual acuity (VA), IOP and anterior and posterior segment findings were recorded and compared before and after surgical treatment.

Results: The average age of all patients was 60.05 years old, while the average period of persistent AACC was 20.05 days. Preoperatively, the average IOP of all included eyes was 44.40 ± 8.42 mmHg despite maximal topical and systemic anti-glaucoma medications and/or laser surgeries, while the average VA was 1.46 ± 0.88 (log MAR). Postoperatively, IOP was well controlled in all patients with an average IOP at 12.06 ± 3.07 mmHg without any anti-glaucoma medications at follow-ups, which was decreased significantly from that in preoperative measurements (P < 0.001). Visual acuity was improved significantly at final follow-up with an average postoperative VA at 0.74 ± 0.77 (log MAR, P < 0.001). Anterior segment inflammation was surprisingly mild with no or minimal inflammatory cells or exudates. Anterior segment configuration was resolved in all the cases. There was no recurrent IOP spike, anterior chamber shallowing or severe complications during an average follow-up of 5.38 months (ranging from 3 to 6 months).

Conclusions: Protracted AACC is a complex situation while a modified surgical strategy of anterior vitrectomy, phaco cataract extraction and IZHV provides a safe and efficient solution.
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http://dx.doi.org/10.1007/s10792-021-01874-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076881PMC
April 2021

Impaired Emotional Self-Referential Processing in First-Episode Schizophrenia.

Front Psychiatry 2021 7;12:591401. Epub 2021 Apr 7.

College of Psychology, Shenzhen University, Shenzhen, China.

Impairments in self-representation are relevant to the expression of psychosis. To date, the characteristics and neural mechanisms of self-impairment in schizophrenia remain unclear. To this end, we used event-related potentials (ERPs) to measure brain activity in 56 first-episode patients with schizophrenia and 56 healthy controls. Participants judged personal trait adjectives regarding themselves, their mothers, or a public person, followed by an unexpected old/new recognition test. The recognition score for mother-reference adjectives was lower than that for self-reference adjectives in patients, while the control group showed comparatively high recognition scores for both self- and mother-referential adjectives. In addition, control subjects recognized more negative words, while patients remembered more positive words. ERP data revealed that controls exhibited typical task effects (self-reference = mother-reference > other-reference) during both automatic attention and effortful encoding periods [indexed by P2 and the late positive potential (LPP), respectively]. In contrast, patients only exhibited the task effect in the P2 amplitude. Moreover, controls exhibited larger P2 amplitudes during encoding negative than positive words, whereas patients had enhanced LPP amplitudes during memory retrieval of positive compared to negative words. These findings demonstrated self-representation dysfunction in first-episode schizophrenic patients in mother (the intimate other) referential processing and the absence of a negative memory bias.
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http://dx.doi.org/10.3389/fpsyt.2021.591401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058190PMC
April 2021

HO-1-mediated ferroptosis as a target for protection against retinal pigment epithelium degeneration.

Redox Biol 2021 Apr 17;43:101971. Epub 2021 Apr 17.

Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, 200011, PR China. Electronic address:

Oxidative stress-mediated retinal pigment epithelium (RPE) degeneration plays a vital role in retinal degeneration with irreversible visual impairment, most notably in age-related macular degeneration (AMD), but a key pathogenic factor and the targeted medical control remain controversial and unclear. In this work, by sophisticated high-throughput sequencing and biochemistry investigations, the major pathologic processes during RPE degeneration in the sodium iodate-induced oxidative stress model has been identified to be heme oxygenase-1 (HO-1)-regulated ferroptosis, which is controlled by the Nrf2-SLC7A11-HO-1 hierarchy, through which ferrous ion accumulation and lethal oxidative stress cause RPE death and subsequently photoreceptor degeneration. By direct knockdown of HO-1 or using HO-1 inhibitor ZnPP, the specific inhibition of HO-1 overexpression has been determined to significantly block RPE ferroptosis. In mice, treatment with ZnPP effectively rescued RPE degeneration and achieved superior therapeutic effects: substantial recovery of the retinal structure and visual function. These findings highlight that targeting HO-1-mediated RPE ferroptosis could serve as an effectively retinal-protective strategy for retinal degenerative diseases prevention, including AMD.
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http://dx.doi.org/10.1016/j.redox.2021.101971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099560PMC
April 2021

Icebreaker-inspired Janus nanomotors to combat barriers in the delivery of chemotherapeutic agents.

Nanoscale 2021 Apr 25;13(13):6545-6557. Epub 2021 Mar 25.

School of Life Science and Engineering, Key Laboratory of Advanced Technologies of Materials, Ministry of Education, Southwest Jiaotong University, Chengdu 610031, P.R. China.

Cancer chemotherapy remains challenging to pass through various biological and pathological barriers such as blood circulation, tumor infiltration and cellular uptake before the intracellular release of antineoplastic agents. Herein, icebreaker-inspired Janus nanomotors (JMs) are developed to address these transportation barriers. Janus nanorods (JRs) are constructed via seed-defined growth of mesoporous silica nanoparticles on doxorubicin (DOX)-loaded hydroxyapatite (HAp) nanorods. One side of JRs is grafted with urease as the motion power via catalysis of physiologically existed urea, and hyaluronidase (HAase) is on the other side to digest the viscous extracellular matrices (ECM) of tumor tissues. The rod-like feature of JMs prolongs the blood circulation, and the self-propelling force and instantaneous digestion of hyaluronic acid along the moving paths promote extravasation across blood vessels and penetration in tumor mass, leading to 2-fold higher drug levels in tumors after JM administration than those with JRs. The digestion of ECM in the diffusion paths is more effective to enhance drug retention and diffusion in tumors compared with enzyme-mediated motion. The ECM digestion and motion capabilities of JMs show no influence on the endocytosis mechanism, but lead to over 3-fold higher cellular uptake than those of pristine JRs. The JM treatment promotes therapeutic efficacy in terms of survival prolongation, tumor growth inhibition and cell apoptosis induction and causes no tumor metastasis to lungs with normal alveolar spaces. Thus, the self-driven motion and instantaneous clearance of diffusion routes demonstrate a feasible strategy to combat a series of biological barriers in the delivery of chemotherapeutic agents in favor of antitumor efficacy.
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http://dx.doi.org/10.1039/d0nr08853fDOI Listing
April 2021

Ganoderic acid A exerted antidepressant-like action through FXR modulated NLRP3 inflammasome and synaptic activity.

Biochem Pharmacol 2021 Apr 20;188:114561. Epub 2021 Apr 20.

School of Medicine, Yunnan University, Kunming 650091, China; The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital & Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing 100088, China. Electronic address:

Major depressive disorder (MDD) is a common, chronic, recurrent disease. The existing drugs are ineffective for approximately half of patients, so the development of antidepressant drugs with novel mechanisms is urgent. Cumulative evidence has shown neuro-inflammation plays a key role in the etiology of major depressive disorder. Clinical studies implicated that bile acids, an important component of gut-brain axis, inhibit neuro-inflammation and mediate the pathophysiology of the MDD. Here, we found that ganoderic acid A (GAA) modulated bile acid receptor FXR (farnesoid X receptor), inhibited brain inflammatory activity, and showed antidepressant effects in the chronic social defeat stress depression model, tail suspension, forced swimming, and sucrose preference tests. GAA directly inhibited the activity of the NLRP3 inflammasome, and activated the phosphorylation and expression of the AMPA receptor by modulating FXR in the prefrontal cortex of mice. If we knocked out FXR or injected the FXR-specific inhibitor z-gugglesterone (GS), the antidepressant effects induced by GAA were completely abolished. These results suggest that GAA modulates the bile acid receptor FXR and subsequently regulates neuroimmune and antidepressant behaviors. GAA and its receptor FXR have potential as targets for the treatment of MDD.
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http://dx.doi.org/10.1016/j.bcp.2021.114561DOI Listing
April 2021

Xinmailong Attenuates Doxorubicin-Induced Lysosomal Dysfunction and Oxidative Stress in H9c2 Cells via HO-1.

Oxid Med Cell Longev 2021 27;2021:5896931. Epub 2021 Mar 27.

Department of Cardiology, Brain Hospital of Hunan Province, Changsha, Hunan, China.

The clinical use of doxorubicin (DOX) is limited by its cardiotoxicity, which is closely associated with oxidative stress. Xinmailong (XML) is a bioactive peptide extracted from American cockroaches, which has been mainly applied to treat chronic heart failure in China. Our previous study showed that XML attenuates DOX-induced oxidative stress. However, the mechanism of XML in DOX-induced cardiotoxicity remains unclear. Heme oxygenase-1 (HO-1), an enzyme that is ubiquitously expressed in all cell types, has been found to take antioxidant effects in many cardiovascular diseases, and its expression is protectively upregulated under DOX treatment. Lysosome and autophagy are closely involved in oxidative stress as well. It is still unknown whether XML could attenuate doxorubicin-induced lysosomal dysfunction and oxidative stress in H9c2 cells via HO-1. Thus, this study was aimed at investigating the involvement of HO-1-mediated lysosomal function and autophagy flux in DOX-induced oxidative stress and cardiotoxicity in H9c2 cells. Our results showed that XML treatment markedly increased cell proliferation and SOD activity, improved lysosomal function, and ameliorated autophagy flux block in DOX-treated H9c2 cells. Furthermore, XML significantly increased HO-1 expression following DOX treatment. Importantly, HO-1-specific inhibitor (Znpp) or HO-1 siRNA could significantly attenuate the protective effects of XML against DOX-induced cell injury, oxidative stress, lysosomal dysfunction, and autophagy flux block. These results suggest that XML protects against DOX-induced cardiotoxicity through HO-1-mediated recovery of lysosomal function and autophagy flux and decreases oxidative stress, providing a novel mechanism responsible for the protection of XML against DOX-induced cardiomyopathy.
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http://dx.doi.org/10.1155/2021/5896931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019640PMC
March 2021

Correlation of the ratio of IgM/IgG concentration to days after symptom onset (IgM/T or IgG/T) with disease severity and outcome in non-critical COVID-19 patients.

Am J Transl Res 2021 15;13(3):1197-1208. Epub 2021 Mar 15.

Department of Respiratory and Critical Care Medicine, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University Nanjing 210002, China.

Background: Correlation of SARS-CoV-2 serum antibodies with COVID-19 development and outcome has not been fully studied. Due to the time dynamic of antibodies, the antibody concentration of the same patient varies greatly at different times during the course of the disease. Therefore, our study used IgM/T or IgG/T (the ratio of serum antibody concentration to days after symptom onset) to reflect the patient's humoral immune status, and analyzed their correlation with COVID-19 development and outcome.

Methods: Clinical data of 50 non-critical COVID-19 patients were retrospectively analyzed. Time-resolved fluorescence immunochromatography was used to quantitatively detect SARS-CoV-2 IgM and IgG. Correlation analysis was performed.

Results: IgM antibody was positive on day 5 of symptom onset, increased within 2 weeks, and then gradually decreased. However, IgG antibody was positive on week 2 of symptom onset and continued to increase since. Additionally, IgM/T, but not IgG/T of recovery period (Spearman ρ=0.17; P=0.283), was negatively correlated with disease course in 2 weeks of symptom onset (Spearman ρ=-0.860; P=0.000). IgG/T of recovery period was positively correlated with clinical classification (Spearman ρ=0.432; P=0.004), number of involved lung lobes (Spearman ρ=0.343; P=0.026), and lung lesions (Spearman ρ=0.472; P=0.002).

Conclusions: Within 2 weeks of symptom onset, higher IgM/T indicates faster recovery and shorter disease course. In recovery period, higher IgG/T suggests more serious disease. IgM/T or IgG/T may predict disease severity and outcome in non-critical COVID-19 patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014342PMC
March 2021

LncRNA LHFPL3-AS1 Promotes Oral Squamous Cell Carcinoma Growth and Cisplatin Resistance Through Targeting miR-362-5p/CHSY1 Pathway.

Onco Targets Ther 2021 31;14:2293-2300. Epub 2021 Mar 31.

Department of Stomatology, Shenzhen Longhua District Central Hospital, Shenzhen, 518000, People's Republic of China.

Background: Oral squamous cell carcinoma (OSCC) is a common oral cancer. The current study aims to elucidate the potential roles of long noncoding RNA (lncRNA) LHFPL3-AS1 in OSCC development.

Methods: Gene expression was measured by qRT-PCR in tumor tissues and cell lines. Loss-of-function assays were performed to analyze the effects of LHFPL3-AS1 on malignant behaviors. Bioinformatics analysis was conducted to explore the downstream signaling pathway of LHFPL3-AS1 in OSCC.

Results: LHFPL3-AS1 was highly expressed in OSCC tissues and cell lines. LHFPL3-AS1 was upregulated in cisplatin-resistant tumor cell lines. LHFPL3-AS1 level was correlated with survival rate. LHFPL3-AS1 knockdown suppressed OSCC proliferation, migration and invasion. LHFPL3-AS1 downregulation reduced cisplatin resistance of OSCC cells. LHFPL3-AS1 was the competing endogenous RNA (ceRNA) for miR-194-5p to enhance CHSY1 expression.

Conclusion: LHFPL3-AS1/miR-362-5p/CHSY1 signaling pathway plays essential roles in regulating OSCC development and cisplatin resistance.
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http://dx.doi.org/10.2147/OTT.S298679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020056PMC
March 2021

Clinical and CT features of mild-to-moderate COVID-19 cases after two sequential negative nucleic acid testing results: a retrospective analysis.

BMC Infect Dis 2021 Apr 8;21(1):333. Epub 2021 Apr 8.

Department of Respiratory and Critical Care Medicine, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, 210002, China.

Background: The clinical and imaging features of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections that progressed to coronavirus disease 2019 (COVID-19) have been explored in numerous studies. However, little is known about these features in patients who received negative respiratory nucleic acid test results after the infections resolved. In this study, we aim to describe these features in a group of Chinese patients.

Methods: This retrospective study includes 51 patients with mild-to-moderate COVID-19 (median age: 34.0 years and 47.1% male) between January 31 and February 28, 2020. Demographic, clinical, laboratory, and computed tomography (CT) imaging data were collected before and after two consecutive negative respiratory SARS-CoV-2 tests.

Results: Following a negative test result, the patients' clinical symptoms continued to recover, but abnormal imaging findings were observed in all moderate cases. Specifically, 77.4% of patients with moderate COVID-19 exhibited multi-lobar lung involvement and lesions were more frequently observed in the lower lobes. The most common CT imaging manifestations were ground-glass opacities (51.6%) and fibrous stripes (54.8%%). Twelve of the 31 patients with moderate COVID-19 underwent repeated chest CT scans after a negative SARS-CoV-2 test. Among them, the ground-glass opacities decreased by > 60% within 1 week in seven patients (58.3%), but by < 5% in four patients (13.8%).

Conclusions: Following a positive and subsequent negative SARS-CoV-2 tests, patients with COVID-19 continued to recover despite exhibiting persistent clinical symptoms and abnormal imaging findings.
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http://dx.doi.org/10.1186/s12879-021-06013-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027977PMC
April 2021

Ganoderic Acid A Attenuates LPS-Induced Neuroinflammation in BV2 Microglia by Activating Farnesoid X Receptor.

Neurochem Res 2021 Apr 5. Epub 2021 Apr 5.

School of Medicine, Yunnan University, 2 Cuihu North Road, Kunming, 650091, Yunnan, People's Republic of China.

Neuroinflammation plays an important role in the onset and progression of neurodegenerative diseases. Microglia-mediated neuroinflammation have been proved to be the main reason for causing the neurodegenerative diseases. Ganoderic acid A (GAA), isolated from Ganoderma lucidum, showed anti-inflammatory effect in metabolism diseases. However, little research has been focused on the effect of GAA in neuroinflammation and the related mechanism. In the present study, lipopolysaccharide(LPS)-stimulated BV2 microglial cells were used to evaluate the anti-inflammatory capacity of GAA. Our data showed that GAA significantly suppressed LPS-induced BV2 microglial cells proliferation and activation in vitro. More strikingly, GAA promoted the conversion of BV2 microglial cells from M1 status induced by LPS to M2 status. Furthermore, GAA inhibited the pro-inflammatory cytokines release and promoted neurotrophic factor BDNF expression in LPS-induced BV2 microglial cells. Finally, we found that the expression of farnesoid-X-receptor (FXR) was prominently downregulated in LPS-stimulated BV2 microglial cells, antagonism of FXR with z-gugglesterone and FXR siRNA can reverse the effect of GAA in LPS-induced BV2 microglial cells. Taking together, our findings demonstrate that GAA can significantly inhibit LPS-induced neuroinflammation in BV2 microglial cells via activating FXR receptor.
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http://dx.doi.org/10.1007/s11064-021-03303-3DOI Listing
April 2021

A Practical Nomogram to Predict Early Death in Advanced Epithelial Ovarian Cancer.

Front Oncol 2021 19;11:655826. Epub 2021 Mar 19.

Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China.

Ovarian cancer is a common gynecological malignancy, most of which is epithelial ovarian cancer (EOC). Advanced EOC is linked with a higher incidence of premature death. To date, no effective prognostic tools are available to evaluate the possibility of early death in patients with advanced EOC. Advanced (FIGO stage III and IV) EOC patients who were enrolled in the Surveillance, Epidemiology, and End Results database between 2004 and 2015 were regarded as subjects and studied. We aimed to construct a nomogram that can deliver early death prognosis in patients with advanced EOC by identifying crucial independent factors using univariate and multivariate logistic regression analyses to help deliver accurate prognoses. In total, 13,403 patients with advanced EOC were included in this study. Three hundred ninety-seven out of a total of 9,379 FIGO stage III patients died early. There were 4,024 patients with FIGO stage IV, 414 of whom died early. Nomograms based on independent prognostic factors have the satisfactory predictive capability and clinical pragmatism. The internal validation feature of the nomogram demonstrated a high level of accuracy of the predicted death. By analyzing data from a large cohort, a clinically convenient nomogram was established to predict premature death in advanced EOC. This tool can aid clinicians in screening patients who are at higher risk for tailoring treatment plans.
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http://dx.doi.org/10.3389/fonc.2021.655826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017286PMC
March 2021

Soil nitrogen dynamics at a regional scale along a precipitation gradient in secondary grassland of China.

Sci Total Environ 2021 Mar 26;781:146736. Epub 2021 Mar 26.

Key Laboratory of Soil Ecology and Health in Universities of Yunnan Province, School of Ecology and Environmental Sciences, Yunnan University, Kunming 650091, PR China. Electronic address:

The availability of soil inorganic nitrogen (N) is primarily regulated by the rates of soil N transformation, including mineralization, ammonification, nitrification, and denitrification, and are sensitive to climate, plant, and soil factors. However, the interactive effects among these factors regulating soil N transformation rates in ecosystems across large spatial scales remain unclear. Here, we investigated the spatial patterns of the potential N mineralization, nitrification, ammonification, and denitrification rates in relation to plant traits and soil edaphic conditions across a 600-km precipitation gradient in secondary grasslands of South China. The soil potential N mineralization and nitrification rates significantly increased with increasing precipitation. However, the soil potential N ammonification and denitrification rates did not significantly vary with precipitation. Moreover, the soil potential N nitrification and denitrification rates significantly increased with increasing soil pH, whereas the potential N mineralization and ammonification rates decreased with increasing soil pH. The soil potential N mineralization rate was positively correlated with soil labile N but negatively correlated with soil recalcitrant C and N contents. Our results revealed that changes in soil NH-N and pH along precipitation gradients primarily controlled the potential N mineralization, nitrification, and ammonification rates. In contrast, soil NO-N, soil pH, and plant N inputs predominantly regulated the potential N denitrification rate. Overall, our results reveal that soil N transformation varies along the precipitation gradient, and these results need to be considered when studying the effects of climate change on N cycling in grassland ecosystems across diverse environments.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146736DOI Listing
March 2021

A series of carboxymethyl cellulose-based antimicrobial peptide mimics were synthesized for antimicrobial applications.

Carbohydr Polym 2021 Jun 16;261:117822. Epub 2021 Feb 16.

Guangdong Institute of Microbiology, Guangdong Academy of Sciences, State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Open Laboratory of Applied Microbiology, Guangzhou 510070, PR China. Electronic address:

Inspired by antimicrobial peptides (AMP) which could alleviate drug resistance pressure, antimicrobial peptide mimics (AMPMs) were designed timely. Here, carboxymethyl cellulose (CMC) -based AMPMs were constructed by introducing different diamines on CMC effectively. Firstly, CMC was degraded to be oligomers with different molecular weights, followed by amination reactions with different diamines respectively. After protonation, a series of AMPMs with different structures were synthesized successfully. Their antibacterial effect has been evaluated by dynamic growth curves and microdilution method. The images snapped by the confocal laser scanning microscope and transmission electron microscope have fully proved its great lethality. And the antibacterial mechanism measured by flow cytometry analysis and zeta potential detection demonstrated that the destruction of membrane potential leads to bacteria death. The excellent blood compatibility and negligible drug resistance has also been confirmed. In addition, the synthesis method is simple and environmental-friendly.
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http://dx.doi.org/10.1016/j.carbpol.2021.117822DOI Listing
June 2021

Identification of long noncoding RNAs with machine learning methods: a review.

Brief Funct Genomics 2021 Mar 23. Epub 2021 Mar 23.

Second Affiliated Hospital, Harbin Medical University, Harbin, China.

Long noncoding RNAs (lncRNAs) are noncoding RNAs with a length greater than 200 nucleotides. Studies have shown that they play an important role in many life activities. Dozens of lncRNAs have been characterized to some extent, and they are reported to be related to the development of diseases in a variety of cells. However, the biological functions of most lncRNAs are currently still unclear. Therefore, accurately identifying and predicting lncRNAs would be helpful for research on their biological functions. Due to the disadvantages of high cost and high resource-intensiveness of experimental methods, scientists have developed numerous computational methods to identify and predict lncRNAs in recent years. In this paper, we systematically summarize the machine learning-based lncRNAs prediction tools from several perspectives, and discuss the challenges and prospects for the future work.
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http://dx.doi.org/10.1093/bfgp/elab017DOI Listing
March 2021

Organic multicomponent microparticle libraries.

Nat Commun 2021 03 23;12(1):1838. Epub 2021 Mar 23.

Department of Chemistry, School of Science, Tianjin University, Tianjin, P. R. China.

Multimetallic nanostructures can be synthesized by integrating up to seven or eight metallic elements into a single nanoparticle, which represent a great advance in developing complex multicomponent nanoparticle libraries. Contrary, organic micro- and nanoparticles beyond three π-conjugated components have not been explored because of the diversity and structural complexity of molecular assemblies. Here, we report a library of microparticles composed of an arbitrary combination of four luminescent organic semiconductors. We demonstrate that the composition and emission color of each domain as well as its spatial distribution can be rationally modulated. Unary, binary, ternary, and quaternary microparticles are thus realized in a predictable manner based on the miscibility of the components, resulting in mixed-composition phases or alloyed or phase separated heterostructures. This work reports a simple yet available synthetic methodology for rational modulation of organic multicomponent microparticles with complex architectures, which can be used to direct the design of functional microparticles.
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http://dx.doi.org/10.1038/s41467-021-22060-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988115PMC
March 2021

β-Amyloid Peptide 1-42-Conjugated Magnetic Nanoparticles for the Isolation and Purification of Glycoproteins in Egg White.

ACS Appl Mater Interfaces 2021 Mar 17;13(12):14028-14036. Epub 2021 Mar 17.

Institute of Translational Medicine, Department of Pharmacy, Shenyang Medical College, Shenyang 110034, China.

Aβ-conjugated magnetic nanoparticles, Aβ@MNP, were prepared by covalently coupling Aβ to hyperbranched polyethyleneimine (PEI)-modified magnetic nanoparticles via -(3-dimethylaminopropyl)-'-ethylcarbodiimide hydrochloride (EDC). Aβ's high binding capacity to glycosyl groups facilitates Aβ@MNP composite to be a promising selective adsorbent for glycoproteins in egg whites. In our study, under conditions of pH 4.0, the adsorption efficiency of Aβ@MNP composite for ovalbumin (100 μg mL) was 98.4% and its maximum adsorption capacity was 344.8 mg g ; under the condition of pH 4.0 and 200 mmol L NaCl, its adsorption efficiencies for ovalbumin and ovotransferrin were 96.9% and 60.0%, respectively. According to these primary data, in practice, ovalbumin was removed from egg white by Aβ@MNP composite at pH 4.0 (step I), and then after adding NaCl until the final salt concentration reached 200 mmol L (pretreated egg white), we utilized the same adsorbent to further isolate/purify glycoproteins (step II). SDS-PAGE results showed that Aβ@MNP composite could largely remove ovalbumin in step I and could isolate/purify the remaining ovalbumin and ovotransferrin in step II. LC-MS/MS analysis results showed that the removal of ovalbumin reduced its percentage in egg white samples from 32.93% to 11.05% in step I and the remaining ovalbumin and ovotransferrin were enriched in step II, where the final percentage reached 11.6% and 12.6%, respectively. In summary, 81 protein species were identified after two-step extraction with Aβ@MNP on egg white, while only 46 protein species were identified directly from raw egg white without any pretreatment. This work well illustrates the excellent adsorption performance of Aβ@MNP composite to glycoproteins and its potential in the application of proteomic studies on low-abundance proteins in egg white.
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http://dx.doi.org/10.1021/acsami.1c02356DOI Listing
March 2021

Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Buyang Huanwu Decoction in the Treatment of Ischemic Stroke.

Evid Based Complement Alternat Med 2021 26;2021:8815447. Epub 2021 Feb 26.

Neurology Department of Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China.

Methods: The bioactive components and potential targets of BHD were screened by TCMSP, BATMAN-TCM, ETCM, and SymMap databases. Besides, compounds that failed to find the targets from the above databases were predicted through STITCH, SwissTargetPrediction, and SEA. Moreover, six databases were searched to mine targets of IS. The intersection targets were obtained and analyzed by GO and KEGG enrichment. Furthermore, BHD-IS PPI network, compound-target network, and herb-target-pathway network were constructed by Cytoscape 3.6.0. Finally, AutoDock was used for molecular docking verification.

Results: A total of 235 putative targets were obtained from 59 active compounds in BHD. Among them, 62 targets were related to IS. PPI network showed that the top ten key targets were IL6, TNF, VEGFA, AKT1, etc. The enrichment analysis demonstrated candidate BHD targets were more frequently involved in TNF, PI3K-Akt, and NF-kappa B signaling pathway. Network topology analysis showed that was the main herb in BHD, and the key components were quercetin, beta-sitosterol, kaempferol, stigmasterol, etc. The results of molecular docking showed the active components in BHD had a good binding ability with the key targets.

Conclusions: Our study demonstrated that BHD exerted the effect of treating IS by regulating multitargets and multichannels with multicomponents through the method of network pharmacology and molecular docking.
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http://dx.doi.org/10.1155/2021/8815447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937485PMC
February 2021

Progress on functional mechanisms of colorectal cancer causal SNPs in post-GWAS.

Yi Chuan 2021 Mar;43(3):203-214

Department of Pathology, School of Medicine, Zhejiang University, Hangzhou 310058, China;Department of Medical Oncology of The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310058, China;Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou 310058, China;

Colorectal cancer (CRC) is caused by genetic and environmental factors, and the genetic component plays a significant role in CRC development. Currently, genome-wide association studies (GWAS) have identified a large number of genetic loci associated with CRC risk. In the post-GWAS era, more and more efforts focus on deciphering the biological mechanisms behind these potential causal variants by using multi-omics data and functional experiments. Many analyses have revealed that most risk single nucleotide polymorphisms (SNPs) are located in non-coding regions and these variants may regulate the expression of target genes by altering the transcription factor-binding motif, epigenetic modification, chromatin accessibility or 3D genome conformation. Results obtained from post-GWAS era have highlighted the possibility of moving from association to function. In this review, we summarize the current status of CRC post-GWAS studies and discusses the clinical application as well as future directions of CRC GWAS, in order to better gain insight into the molecular basis of CRC and provide evidence for prevention.
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http://dx.doi.org/10.16288/j.yczz.20-320DOI Listing
March 2021

Joint association of cigarette smoking and PM with COPD among urban and rural adults in regional China.

BMC Pulm Med 2021 Mar 15;21(1):87. Epub 2021 Mar 15.

Nanjing Municipal Center for Disease Control and Prevention, 3, Zizhulin, Nanjing, 210037, China.

Background: Cigarette smoking and PM are important risk factors of Chronic Obstructive Pulmonary Disease (COPD). However, the joint association of cigarette smoking and PM with COPD is unknown.

Methods: A community-based study was conducted among urban and rural adults aged 40 + years between May and December of 2015 in Jiangsu Province, China. The outcome variable was spirometry-defined COPD. Explanatory measures were smoking status (non-smokers or smokers) and PM exposure [low level (< 75 μg/m) or high level (≥ 75 μg/m)]. Mixed-effects logistic regression models were applied to calculate the odds ratio (OR) and 95% confidence interval (CI) to investigate the associations of cigarette smoking and PM with COPD.

Results: The prevalence of COPD was 11.9% (95% CI = 10.9%, 13.0%) within the overall 3407 participants in this study. After adjustment for potential confounders and community-level clustering effect, smokers tended to develop COPD relative to non-smokers (OR = 2.46, 95% CI 1.76, 3.43), while only smokers exposed to high level PM were more likely to experience COPD (OR = 1.36; 95% CI 1.01, 1.83) compared to their counterparts exposed to low level PM. Meanwhile, compared to non-smokers who exposed to low level PM, non-smokers who exposed to high level PM (OR = 1.10, 95% CI 0.74, 1.64), smokers who exposed to low (OR = 2.22, 95% CI 1.51, 3.27) or high level PM (OR = 3.14, 95% CI 2.15, 4.59) were, respectively, more like to develop COPD.

Conclusions: Cigarette smoking was positively associated with COPD among overall participants, while PM was in positive relation to COPD among smokers only. Moreover, cigarette smoking and PM might have an additive effect on the risk of COPD among adult smokers aged 40 years or older in China.
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http://dx.doi.org/10.1186/s12890-021-01465-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962238PMC
March 2021

Sex-Specific Associations of Polymorphisms With Schizophrenia in a Han Chinese Cohort.

Front Genet 2021 23;12:627874. Epub 2021 Feb 23.

Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.

: To investigate the effects of microRNA-137 () polymorphisms (rs1198588 and rs2660304) on the risk of schizophrenia in a Han Chinese population. : Schizophrenia was diagnosed according to the DSM-5. Clinical symptoms and cognitive functions were assessed with the Positive and Negative Symptom Scale (PANSS) and Brief Assessment of Cognition in Schizophrenia (BACS), respectively. The polymorphisms were genotyped by improved multiplex ligation detection reaction (iMLDR) technology in 1,116 patients with schizophrenia and 1,039 healthy controls. : Significant associations were found between schizophrenia and in the distributions of genotypes ( = 0.037 for rs1198588; = 0.037 for rs2660304, FDR corrected) and alleles ( = 0.043 for rs1198588; = 0.043 for rs2660304, FDR corrected) of two SNPs. When the population was stratified by sex, we found female-specific associations between and schizophrenia in terms of genotype and allele distributions of rs1198588 ( = 4.41, = 0.036 and = 4.86, = 0.029, respectively, FDR corrected) and rs2660304 ( = 4.74, =0.036 and = 4.80, = 0.029, respectively, FDR corrected). Analysis of the haplotype rs1198588-rs2660304 showed a significant association with schizophrenia in haplotype T-T [ = 4.60, = 0.032, OR = 1.32, 95% CI (1.02-1.70)]. Then, significant female-specific associations were found with the haplotypes T-T and G-A [ = 4.92, = 0.027, OR = 1.62, 95% CI (1.05-2.50); = 4.42, = 0.035, OR = 0.62, 95% CI (0.39-0.97), respectively]. When the TT genotype of rs1198588 was compared to the GT+GG genotype, a clinical characteristics analysis also showed a female-specific association in category instances ( = 2.76, = 0.042, FDR corrected). : The polymorphisms within the gene are associated with susceptibility to schizophrenia, and a female-specific association of with schizophrenia was reported in a Han Chinese population.
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http://dx.doi.org/10.3389/fgene.2021.627874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942225PMC
February 2021

Ganoderma lucidum polysaccharides ameliorated depression-like behaviors in the chronic social defeat stress depression model via modulation of Dectin-1 and the innate immune system.

Brain Res Bull 2021 Jun 8;171:16-24. Epub 2021 Mar 8.

Yunnan University, School of Medicine, 2 Cuihu North Road, Kunming, Yunnan, 650091, PR China. Electronic address:

Major depressive disorder (MDD) is a prevalent, chronic, and recurrent disease. At least one-third of patients have treatment-resistant depression; therefore, there is an urgent need for novel drug development. Cumulative studies have suggested an inflammatory mechanism for the pathophysiology of MDD. Ganoderma lucidum polysaccharides (GLP) is an anti-inflammatory and immunomodulatory agent. Here, we found that an injection of GLP led to a rapid and robust antidepressant effect after 60 min in the tail suspension test. This antidepressant effect remained after 5 days of treatment with GLP in the forced swim test. Unlike psychostimulants, GLP did not show a hyperactive effect in the open field test. After 60 min or 5 days of treatment, GLP exhibited an antidepressant effect in a chronic social defeat stress (CSDS) depression animal model. Moreover, after 5 days of treatment, GLP attenuated the expression of the proinflammatory cytokines IL-1β and TNF-α, enhanced the expression of the anti-inflammatory cytokine IL-10 and the neurotrophic factor BDNF, and inhibited the activation of microglia and proliferation of astrocytes in the hippocampus of CSDS mice. In addition, after 5 days of treatment, GLP significantly enhanced GluA1 S845 phosphorylation as well as GluA1 and GluA2 expression levels in the hippocampus of CSDS mice. To determine whether the antidepressant effect was mediated by Dectin-1, we found that GLP treatment enhanced Dectin-1 expression in the hippocampus in CSDS mice, and the Dectin-1-specific inhibitor laminarin almost completely blocked the antidepressant effect of GLP. This study identified GLP, an agonist of Dectin-1, as a novel and rapid antidepressant with clinical potential and multiple beneficial mechanisms, particularly in regulating the neuroimmune system and, subsequently, AMPA receptor function.
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http://dx.doi.org/10.1016/j.brainresbull.2021.03.002DOI Listing
June 2021