Publications by authors named "Lei Chen"

4,199 Publications

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Marfan syndrome with recurrent lower left posterior toothache as the first symptom: A report on a rare case.

J Endod 2021 May 11. Epub 2021 May 11.

Departments of Oral Emergency, Stomatological Hospital, Southern Medical University, Guangzhou, Guangdong, China. Electronic address:

Marfan syndrome (MFS) is a life-threatening connective tissue disorder that affects multiple organs and systems. We report a case of MFS with recurrent lower left posterior toothache as the first symptom. A 23-year-old Asian man walked into the dental emergency room with a chief complaint of recurrent spontaneous and intermittent toothache in his lower left posterior tooth region, mimicking acute symptomatic pulpitis. He self-reported a relatively healthy medical status, without any hereditary disease. However, his disproportionately elongated body structure, high myopia, and positive wrist sign were immediately recognizable. Although there were no remarkable findings on dental examination, pectus carinatum deformity and abnormal blood pressure were later detected. He was immediately referred to a cardiologist in a medical hospital. Timely diagnosis of MFS and early surgical intervention helped avoid severe lethal consequences. The symptoms of toothache completely resolved after surgery.
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http://dx.doi.org/10.1016/j.joen.2021.05.002DOI Listing
May 2021

Identifying protein subcellular locations with embeddings-based node2loc.

IEEE/ACM Trans Comput Biol Bioinform 2021 May 14;PP. Epub 2021 May 14.

Identifying protein subcellular locations is an important topic in protein function prediction. Interacting proteins may share similar locations. Thus, it is imperative to infer protein subcellular locations by taking protein-protein interactions (PPIs) into account. In this study, we present a network embedding-based method, node2loc, to identify protein subcellular locations. node2loc first learns distributed embeddings of proteins in a protein-protein interaction (PPI) network using node2vec. Then the learned embeddings are further fed into a recurrent neural network (RNN). To resolve the severe class imbalance of different subcellular locations, Synthetic Minority Over-sampling Technique (SMOTE) is applied to artificially synthesize proteins for minority classes. node2loc is evaluated on our constructed human benchmark dataset with 16 subcellular locations and yields a Matthews correlation coefficient (MCC) value of 0.800, which is superior to baseline methods. In addition, node2loc yields a better performance on a Yeast benchmark dataset with 17 locations. The results demonstrate that the learned representations from a PPI network have certain discriminative ability for classifying protein subcellular locations. However, node2loc is a transductive method, it only works for proteins connected in a PPI network, and it needs to be retrained for new proteins. In addition, the PPI network needs be annotated to some extent with location information.
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http://dx.doi.org/10.1109/TCBB.2021.3080386DOI Listing
May 2021

Three-dimensional microspheres constructed with MoS nanosheets supported on multiwalled carbon nanotubes for optimized sodium storage.

Nanoscale 2021 May 14. Epub 2021 May 14.

School of Pharmaceutical Chemical and Materials Engineering, Taizhou University, Taizhou, 318000, P. R. China.

Molybdenum disulfide (MoS2) has been regarded as a promising anode material in the field of sodium-ion batteries (SIBs), with the advantages of high theoretical capacity and large interlayer spacings. Unfortunately, its intrinsic poor electrical conductivity and large volume changes during the sodiation/desodiation reactions still limit its practical application. To deal with this shortcoming, we built MoS2 nanosheet/multiwalled carbon nanotube (denoted as MoS2-MSs/MWCNTs) composites with a three-dimensional (3D) micro-spherical structure, assembled in situ from MoS2 nanosheets. These nanosheets are connected to each other by the MWCNTs network, which provides a highly conductive pathway for electrons/ions through interparticle and intraparticle interfaces, accelerating charge transfer and ion diffusion capabilities. More importantly, the carbon network can boost electrical conductivity and relieve structural strain. Consequently, the as-prepared MoS2-MSs/MWCNTs composite presents a high reversible specific capacity of 519 mA h g-1 at 0.1 A g-1 after 100 cycles with a capacity retention of 94.4% and excellent rate performance (227 mA h g-1 at 10 A g-1). Outstanding cycling stability was also achieved (327.1 mA h g-1 over 1000 cycles at 2 A g-1) and was characterized by scanning electron microscopy (SEM) analysis. Our findings provide a simple and effective strategy to explore anode materials with advanced sodium storage properties.
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http://dx.doi.org/10.1039/d1nr01736eDOI Listing
May 2021

The land carrying capacity and environmental risk assessment of livestock and poultry breeding considering crop planting.

Environ Sci Pollut Res Int 2021 May 12. Epub 2021 May 12.

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing, 100875, People's Republic of China.

At present, the contradiction between survival and ecology necessitates the integration of crop planting, chemical fertilizer application, and livestock and poultry breeding. Reasonably integrated crop-livestock systems (ICLSs) have become an important part of regional ecological and agricultural development. In this study, the relationship between manure nutrient demands for crops and manure nutrient supply from livestock is considered based on the balance of ICLSs in Jiangxi Province, China. The land carrying capacity index and potential of livestock breeding under uncoordinated systems are further discussed. The study also addresses water environmental risk due to surplus nutrients by integrating a traditional land carrying capacity framework and hydrological model. The results show that phosphorus absorption in land areas is the main limiting factor for the development of the livestock and poultry industries. In addition, manure nutrient demand exceeded supply in most districts, while the unbalanced regions with nutrient pollution are located in the upper and middle reaches of the Ganjiang basin. In addition, expanding the crop demand for manure or increasing the manure collection rate will help reduce environmental harm; however, attention should be paid to the risk of excessive manure returns. Additional livestock manure can be transferred to regions with developed crop planting systems. This study supports more harmonious and common ICLSs construction.
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http://dx.doi.org/10.1007/s11356-021-14310-wDOI Listing
May 2021

Knockout of Formyl Peptide Receptor-1 Attenuates Cigarette Smoke-Induced Airway Inflammation in Mice.

Front Pharmacol 2021 26;12:632225. Epub 2021 Apr 26.

Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University and Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, Chengdu, China.

The formyl peptide receptor-1 (FPR-1) has been reported to be implicated in the regulation of inflammatory disorders, while its role in cigarette smoke (CS)-induced airway inflammation has not been fully explained. In this study, we investigated the role of FPR-1 in CS-induced airway inflammation and the possible mechanism through gene knockout (KO) technology and transcriptional study. FPR-1 KO or wild-type C57BL/6 mice were exposed to mainstream CS to establish an airway inflammation model. Cell counts and pro-inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF). Lung tissues were collected for histological examination, polymerase chain reaction, Western blot, transcriptomic gene study, and related bioinformatics analysis. CS exposure induced significant histological inflammatory changes, increased neutrophils, and pro-inflammatory cytokines in the BALF of wild-type mice, which were all attenuated by KO of FPR-1. The transcriptomic gene study showed a total of 198 up-regulated genes and 282 down-regulated genes in mouse lungs. Bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) suggested these differentiated expressed genes were significantly related to the immune, chemotaxis responses, and cross-talked with a complicated network of signaling pathways including NF-κB. Western blot validated that KO of FPR-1 inhibited CS-induced NF-κB activation. Knockout of FPR-1 significantly ameliorates CS-induced airway inflammation in mice, possibly via its related immune-chemotaxis responses and inhibition of NF-κB activation.
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http://dx.doi.org/10.3389/fphar.2021.632225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110203PMC
April 2021

Phragmunis A suppresses glioblastoma through the regulation of MCL1-FBXW7 by blocking ELK1-SRF complex-dependent transcription.

Neurochem Int 2021 May 9:105051. Epub 2021 May 9.

Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, 3002# Sungang Road, Futian District, Shenzhen 518035, China. Electronic address:

Glioblastoma (GBM) is a highly aggressive brain tumour. During screening work, we found a new compound named phragmunis A (PGA), which is derived from the fruitbody of Trogia venenata, exhibits a potential cytotoxic effect on patient-derived recurrent GBM cells and temozolomide (TMZ)-resistant cell lines. The present study was designed to investigate the potential molecular mechanism of the anti-glioma effects of PGA in vitro and in vivo. Studies investigating the mechanism revealed that PGA diminished the binding efficiency of ETS family of transcription factor (ELK1) and Serum response factor (SRF), and suppressed ELK1-SRF complex-dependent transcription, which decreased the transcriptional levels of downstream genes Early growth response protein 1 (EGR1)-Polycomb ring finger (BMI1), thus inducing the imbalanced regulation between Myeloid cell leukaemia-1 (MCL1) and F-Box and WD repeat domain containing 7 (FBXW7). Finally, orthotopic xenograft models were established to confirm the anti-glioma effect of PGA on tumour growth. We showed, for the first time, that the cytotoxic effects of PGA occurred by inducing MCL1 inhibition and FBXW7 activation by blocking ELK1-SRF complex-dependent transcription. The blockage of ELK1-mediated transcription resulted in the suppression of EGR1-BMI1, which led to the upregulation of FBXW7 expression and downregulation of MCL1. These findings suggested that PGA could be a therapeutic drug candidate for the treatment of recurrent GBM by targeting the ELK1-SRF complex.
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http://dx.doi.org/10.1016/j.neuint.2021.105051DOI Listing
May 2021

Atroposelective Synthesis of Axially Chiral 4-Aryl α-Carbolines via -Heterocyclic Carbene Catalysis.

Org Lett 2021 May 11. Epub 2021 May 11.

State Key Laboratory of Natural Medicines, Department of Organic Chemistry, China Pharmaceutical University, Nanjing 210009, P. R. China.

The first catalytic asymmetric construction of axially chiral 4-aryl α-carboline skeletons has been accomplished through an -heterocyclic carbene (NHC)-catalyzed atroposelective formal [3 + 3] annulation of 4-nitrophenyl 3-arylpropiolates with 2-sulfonamidoindolines. The synthetic utility of the title compounds has been demonstrated by the diverse late-stage structural modifications. Density functional theory calculations were also conducted to illuminate the key factors for controlling the origin of the enantioselectivity. This strategy not only provides an efficient pathway to access axially chiral α-carboline atropisomers but also offers a novel catalytic enantioselective mode for the construction of axially chiral heterobiaryls by using NHC-bound alkynyl acylazoliums.
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http://dx.doi.org/10.1021/acs.orglett.1c01221DOI Listing
May 2021

[Expression and characterization of a novel halohydrin dehalogenase from Rhodospirillaceae bacterium].

Sheng Wu Gong Cheng Xue Bao 2021 Apr;37(4):1298-1311

School of Biotechnology, East China University of Science and Technology, Shanghai 200237, China.

As a class of multifunctional biocatalysts, halohydrin dehalogenases are of great interest for the synthesis of chiral β-substituted alcohols and epoxides. There are less than 40 halohydrin dehalogenases with relatively clear catalytic functions, and most of them do not meet the requirements of scientific research and practical applications. Therefore, it is of great significance to excavate and identify more halohydrin dehalogenases. In the present study, a putative halohydrin dehalogenase (HHDH-Ra) from Rhodospirillaceae bacterium was expressed and its enzymatic properties were investigated. The HHDH-Ra gene was cloned into the expression host Escherichia coli BL21(DE3) and the target protein was shown to be soluble. Substrate specificity studies showed that HHDH-Ra possesses excellent specificity for 1,3-dichloro-2-propanol (1,3-DCP) and ethyl-4-chloro-3-hydroxybutyrate (CHBE). The optimum pH and temperature for HHDH-Ra with 1,3-DCP as the reaction substrate were 8.0 and 30 °C, respectively. HHDH-Ra was stable at pH 6.0-8.0 and maintained about 70% of its original activity after 100 h of treatment. The thermal stability results revealed that HHDH-Ra has a half-life of 60 h at 30 °C and 40 °C. When the temperature is increased to 50 °C, the enzyme still has a half-life of 20 h, which is much higher than that of the reported enzymes. To sum up, the novel halohydrin dehalogenase from Rhodospirillaceae bacterium possesses good temperature and pH stability as well as catalytic activity, and shows the potential to be used in the synthesis of chemical and pharmaceutical intermediates.
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http://dx.doi.org/10.13345/j.cjb.200719DOI Listing
April 2021

Apatinib as second-line or later therapy in patients with advanced hepatocellular carcinoma (AHELP): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial.

Lancet Gastroenterol Hepatol 2021 May 7. Epub 2021 May 7.

Department of Intervention, Fujian Cancer Hospital, Fuzhou, China.

Background: Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma.

Methods: AHELP was a randomised, double-blind, placebo-controlled, phase 3 trial done at 31 hospitals in China, in patients (aged ≥18 years) with advanced hepatocellular carcinoma who had previously been refractory or intolerant to at least one line of systemic chemotherapy or targeted therapy. Patients were randomly assigned (2:1) to receive apatinib 750 mg or placebo orally once daily in 28-day treatment cycles. Group allocation was done with a central randomisation system, with a block size of six, and was stratified by Eastern Cooperative Oncology Group performance status, previous sorafenib treatment, and presence of vascular invasion or extrahepatic metastasis. The primary endpoint was overall survival, which was defined as time from randomisation to death from any cause, and was analysed in patients who were randomly assigned and received at least one dose of the study drug. Safety analyses were done in patients who received at least one dose of the study treatment and had post-dose safety assessments. This trial is registered with ClinicalTrials.gov, NCT02329860.

Findings: Between April 1, 2014, and May 3, 2017, 400 eligible patients were randomly assigned to receive apatinib (n=267) or placebo (n=133). Seven patients (six in the apatinib group and one in the placebo group) did not receive study treatment and were excluded from efficacy analyses. Overall survival was significantly improved in the apatinib group compared with the placebo group (median 8·7 months [95% CI 7·5‒9·8] vs 6·8 months [5·7‒9·1]; hazard ratio 0·785 [95% CI 0·617‒0·998], p=0·048). 387 patients (257 in the apatinib group and 130 in the placebo group) had a safety assessment after study treatment and were included in safety analyses. The most common treatment-related adverse events of grade 3 or 4 were hypertension (71 [28%] patients in the apatinib group vs three [2%] in the placebo group), hand-foot syndrome (46 [18%] vs none), and decreased platelet count (34 [13%] vs one [1%]). 24 (9%) patients in the apatinib group and 13 (10%) in the placebo group died due to adverse events, but none of these deaths were deemed to be related to treatment by investigators.

Interpretation: Apatinib significantly improved overall survival in patients with pretreated advanced hepatocellular carcinoma compared with placebo, with a manageable safety profile.

Funding: Jiangsu Hengrui Medicine.
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http://dx.doi.org/10.1016/S2468-1253(21)00109-6DOI Listing
May 2021

Starch/tea polyphenols nanofibrous films for food packaging application: From facile construction to enhance mechanical, antioxidant and hydrophobic properties.

Food Chem 2021 Apr 22;360:129922. Epub 2021 Apr 22.

National R&D Center for Se-rich Agricultural Products Processing, Hubei Engineering Research Center for Deep Processing of Green Se-rich Agricultural Products, School of Modern Industry for Selenium Science and Engineering, Wuhan Polytechnic University, Wuhan 430023, PR China.

Starch based food packaging has been receiving increasing attention. However, the inherent poor properties of starch restrict its practical applications in the versatile material science field. In this study, a fast, simple, and environmentally friendly route to construct polyfunctional starch/tea polyphenols nanofibrous films (STNFs) by one-step temperature-assisted electrospinning was developed. The effects of introduction of tea polyphenols (TP) on the mechanical and antioxidant activity of STNFs were comprehensively investigated. Results of ABTS·+ free radical scavenging assay showed that the antioxidant activity of STNFs was endowed by addition of TP with optimum mechanical properties confirmed by tensile test. More interestingly, the hydrophobicity of STNFs was improved dramatically with increasing cross-linking time as indicated by water contact angle (WCA) measurement showing no effect on the antioxidant activity of the films. The results of this work offer a major step forward to promote functional starch-based materials for sustainable application in food packaging.
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http://dx.doi.org/10.1016/j.foodchem.2021.129922DOI Listing
April 2021

The efficacy of radiofrequency ablation versus cryoablation in the treatment of single hepatocellular carcinoma: A population-based study.

Cancer Med 2021 May 7. Epub 2021 May 7.

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

Background: Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC), but it is difficult to use against tumors in some locations and often leads to incomplete ablation as a result of the heat-sink effect. This study was conducted to evaluate the efficacy of cryoablation compared with that of RFA in the treatment of single HCC.

Methods: This retrospective study was conducted based on the Surveillance, Epidemiology, and End Results (SEER) database. From 2004 to 2015, patients aged 40 to 79 diagnosed with HCC were included in the study. A propensity score matching (PSM) model was used to reduce selection biases.

Results: Before PSM, the median overall survival (mOS) and median cancer-specific survival (mCSS) in the RFA group were slightly longer than those in the cryoablation group (p > 0.05). In the subgroup analysis, the mOS and mCSS of patients with tumor sizes <3, 3-5, and >5 cm who received RFA treatment were longer than those of patients given cryoablation treatment, but there was no significant difference (p > 0.05). Similar results were presented in patients at American Joint Committee on Cancer (AJCC) stages I and II. After PSM, the mOS and mCSS were slightly better in the RFA group than the cryoablation group but without significant differences. Univariate and multivariate analysis showed that cryoablation treatment was not an unfavorable factor for OS and CSS before or after PSM (p > 0.05). In the multivariable competing risk model, non-cancer-specific death was taken as a competing factor and cryoablation was also not unfavorable for the survival of patients before and after PSM (p > 0.05).

Conclusion: Cryoablation is non-inferior to RFA therapy for single HCC patients without lymph node invasion or distant metastasis.
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http://dx.doi.org/10.1002/cam4.3923DOI Listing
May 2021

Determination and dietary risk assessment of 284 pesticide residues in local fruit cultivars in Shanghai, China.

Sci Rep 2021 May 6;11(1):9681. Epub 2021 May 6.

Institute for Agro-Food Standards and Testing Technology, Shanghai Academy of Agricultural Sciences, 1000 Jinqi Road, Shanghai, 201403, China.

The presence of pesticide residues has become one of the main risk factors affecting the safety and quality of agro-food. In this study, a multi-residue method for the analysis of 284 pesticides in five local fruit cultivars in Shanghai was developed based on ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The limits of determination and the limits of quantitation of pesticides were 0.6-10 and 2-30 μg/kg, respectively. A total of 44, 10, 10, 18, and 7 pesticides were detected in strawberries, watermelons, melons, peaches, and grapes, respectively. The pesticide levels in 95.0% of the samples were below the maximum residual limits (MRLs) prescribed by China, and in 66.2% of the samples below the EU MRLs. The dietary risk assessment study showed big differences in the chronic and acute exposure risk values among different Chinese consumer groups. Through fruit consumption, children/females showed higher exposure risks than adults/males. But both the risk values were less than 100%, indicating that potential dietary risk induced by the pesticides was not significant for Chinese consumers. Nevertheless, certain measures are needed for both growers and the government in order to decrease the MRL-exceeding rate of pesticide residues and ensure the quality and safety of fruits for consumers.
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http://dx.doi.org/10.1038/s41598-021-89204-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102495PMC
May 2021

Pd-Catalysed direct C(sp)-H fluorination of aromatic ketones: concise access to anacetrapib.

Chem Commun (Camb) 2021 May;57(37):4544-4547

Catalytic Hydrogenation Research Center, State Key Laboratory Breeding Base of Green Chemistry-Synthesis Technology, Key Laboratory of Green Pesticides and Cleaner Production Technology of Zhejiang Province, Zhejiang University of Technology, Hangzhou 310014, P. R. China.

The Pd-cataylsed direct ortho-C(sp2)-H fluorination of aromatic ketones has been developed for the first time. The reaction features good regioselectivity and simple operations, constituting an alternative shortcut to access fluorinated ketones. A concise synthesis of anacetrapib has also been achieved by using late-stage C-H fluorination as a key step.
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http://dx.doi.org/10.1039/d1cc01047fDOI Listing
May 2021

Controlled release of KGF-2 for regulation of wound healing by KGF-2 complexed with "lotus seedpod surface-like" porous microspheres.

J Mater Chem B 2021 May 5. Epub 2021 May 5.

Department of Intensive Care, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Keratinocyte growth factor-2 (KGF-2) can regulate the proliferation and differentiation of keratinocyte, which plays a remarkable role in maintaining normal tissue structure and promoting wound healing. As an effective strategy, KGF-2 solution is widely used in the treatment of wounds in clinical applications. However, KGF-2 in solution cannot achieve sustained release, which results in drug loss and unnecessary waste. Polysaccharide hemostasis microspheres (PHMs) are an ideal drug loading platform due to their special "lotus seedpod surface-like" morphology and structure. Herein, to realize the controllable release of KGF-2, PHMs loaded with KGF-2 (KGF-2@PHMs) were prepared. It was found that the bioavailability of KGF-2 was improved greatly. Most importantly, KGF-2@PHMs can reduce inflammation and accelerate the wound healing process due to the controlled release of KGF-2. KGF-2@PHMs might be a potential alternative strategy for wound healing in future clinical applications.
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http://dx.doi.org/10.1039/d1tb00148eDOI Listing
May 2021

The Landscape of Cell-free HBV Integrations and Mutations in Cirrhosis and Hepatocellular Carcinoma Patients.

Clin Cancer Res 2021 May 4. Epub 2021 May 4.

Berry Oncology Corporation, Beijing, China.

Purpose: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful non-invasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear.

Experimental Design: A cSMART (Circulating Single-Molecule Amplification and Resequencing Technology)-based method (SIM) was developed to simultaneously investigate HBV integration and mutation landscapes on cfDNA with HBV-specific primers covering the whole HBV genome. 481 HCC and 517 liver cirrhosis (LC) patients were recruited in the study.

Results: A total of 6,861 integration breakpoints including TERT and KMT2B were discovered in HCC cfDNA, more than in LC. The concentration of circulating tumor DNA (ctDNA) was positively correlated with the detection rate of these integration hotspots and total HBV integration events in cfDNA. To track the origin of HBV integrations in cfDNA, whole-genome sequencing (WGS) was performed on their paired tumor tissues. The paired comparison of WGS data from tumor tissues and SIM data from cfDNA confirmed most recurrent integration events in cfDNA originated from tumor tissue. The mutational landscape across the whole HBV genome was firstly generated for both HBV genotype C and B. A region from nt1100 to nt1500 containing multiple HCC risk mutation sites (OR>1) was identified as a potential HCC-related mutational hot-zone.

Conclusions: Our study provides an in-depth delineation of HBV integration/mutation landscapes at cfDNA level and did a comparative analysis with their paired tissues. These findings shed light on the possibilities of non-invasive detection of virus insertion/mutation.
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http://dx.doi.org/10.1158/1078-0432.CCR-21-0002DOI Listing
May 2021

Effect of embryo cryopreservation duration on pregnancy-related complications and birthweight after frozen-thawed embryo transfer: a retrospective cohort study.

J Dev Orig Health Dis 2021 May 5:1-10. Epub 2021 May 5.

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.

Frozen embryo transfer (FET) has been adopted by growing number of reproductive medicine centers due to the improved outcome compared with fresh embryo transfer. However, few studies have focused on the impact of embryo cryopreservation duration on pregnancy-related complications and neonatal birthweight. Thus, a retrospective cohort study including all FET cycles with livebirth deliveries in a university affiliated hospital from May 2010 to September 2017 was conducted. These deliveries were grouped by the cryopreservation duration of the transferred embryo (≤3 months, 4-6 months, 7-12 months, and >12 months). The associations between embryo cryopreservation duration and pregnancy-related complications were evaluated among the groups using multinomial logistic regression. Neonatal birthweight was compared according to the stratification of singletons and multiples using multinomial and multilevel logistic regression, respectively. Among all 12,158 FET cycles, a total of 3864 livebirth deliveries comprising 2995 singletons and 1739 multiples were included. Compared with those within 3 months, women undergoing FET after a cryopreservation time longer than 3 months did not show any increased risk of gestational diabetes mellitus, gestational hypertension, preeclampsia, meconium staining of the amniotic fluid, or preterm birth. Furthermore, the risk of lower birthweight, macrosomia, small-for-gestational-age, or large-for-gestational-age for either singletons or multiples was not affected by long-term cryopreservation. In summary, embryo cryopreservation duration does not have negative effects on pregnancy-related complications or birthweight after FET.
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http://dx.doi.org/10.1017/S2040174421000192DOI Listing
May 2021

A biomolecule chiral interface base on BSA for electrochemical recognition of amine enantiomers.

Chirality 2021 May 2. Epub 2021 May 2.

Changzhou University Huaide College, Jingjiang, China.

A composite chiral interface (BSA-MB-MWCNTs) was prepared from bovine serum albumin (BSA), methylene blue (MB), and multi-walled carbon nanotubes (MWCNTs) for chiral recognition of amine enantiomers (1S, 2S)-N,N'-dimethyl-1,2-cyclohexanediamine and (1R, 2R)-N,N'-dimethyl-1,2-cyclohexanediamine. The BSA-based composite was characterized by field emission scanning electron microscopy (FESEM) and ultraviolet-visible spectroscopy (UV-Vis). The electrochemical responses towards the two enantiomers were analyzed via cyclic voltammetry (CV), electrochemical AC impedance method (EIS), and differential-pulse voltammetry (DPV). The experimental results showed that the combination of MWCNTs and BSA could effectively improve the overall identification efficiency, and the peak current displayed by the S-enantiomer is larger, indicating that the prepared chiral surface has stronger interaction with the R-enantiomer. Under optimized condition, the current value of the oxidation peak of the chiral modified electrode showed a good linear relationship towards the amine concentration in the range of 5.0 × 10 to 5.0 × 10 mmol·L . The proposed electrochemical chiral interface is easy to handle and provides a promising electrochemical sensing platform that can be used to identify chiral amine enantiomers.
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http://dx.doi.org/10.1002/chir.23314DOI Listing
May 2021

The relationship among primary anatomic subsite and risk and distribution of second malignant neoplasms in patients with stage I/II diffuse large B-cell lymphoma: An analysis of the surveillance, epidemiology, and end results database.

Transl Oncol 2021 Apr 28;14(7):101106. Epub 2021 Apr 28.

Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Collaborative Innovation Center of Hematology, Huazhong University of Science and Technology, Wuhan, China.

Background: Recent studies have reported that diffuse large B-cell lymphoma (DLBCL) involving different primary extranodal sites have distinct clinicopathological characteristics and prognosis. However, the risk of secondary malignant neoplasms (SMNs) in DLBCL survivors with different primary extranodal sites are unknown.

Methods: A total of 40,714 patients diagnosed with stage I/II DLBCL were included from the Surveillance, Epidemiology, and End Results (SEER) database from 1983 to 2015.The standardized incidence ratio (SIR) and absolute excess risk (AER) were used to assess the risk of SMNs.

Results: The results show that the risk of SMN was significantly higher in extranodal DLBCL than in the US general population (SIR, 1.18; 95% CI, 1.11-1.26), and the risk of developing SMN remains significantly elevated with increased latency. Moreover, there were multiple site-specific risk patterns. There was a 22%, 44%, 66%, 123% and 151% increased risk of SMN 10 years after primary gastrointestinal tract, head/neck, skeletal, lung and liver/pancreas DLBCL diagnosis, respectively. There was a significant decrease risk of SMN with increasing age at diagnosis for primary gastrointestinal tract and skeletal DLBCL. In addition, DLBCL patients with primary sites in the gastrointestinal tract, thyroid and liver/pancreas had the highest incidences of secondary stomach cancer, second thyroid cancer, and second hepatobiliary cancer, respectively, which indicated that the initial site of DLBCL may predict the type of SMN.

Conclusions: The strategies for cancer surveillance after extranodal DLBCL diagnosis may need to be individualized according to the subsite of extranodal DLBCL.
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http://dx.doi.org/10.1016/j.tranon.2021.101106DOI Listing
April 2021

Evaluation of lignin inhibition in anaerobic digestion from the perspective of reducing the hydrolysis rate of holocellulose.

Bioresour Technol 2021 Apr 24;333:125204. Epub 2021 Apr 24.

Heilongjiang Academy of Agricultural Sciences Postdoctoral Programme, Harbin 150086, PR China; Rural Energy & Environmental Protection Institute of Heilongjiang Academy of Agricultural Sciences, Key Laboratory Combining Farming & Animal Husbandry, Key Laboratory of Straw Energy Utilization, Harbin 150086, PR China. Electronic address:

In this study, Anaerobic Digestion Model No. 1 (ADM1) were modified to simulate anaerobic digestion (AD) process of microcrystalline cellulose (MCC) and five lignocellulosic substrates, with the goal of predicting the hydrolysis rates of holocellulose fractions in environments with and without lignin inhibition. After model verification, the hydrolysis rate constant of MCC, i.e., the hydrolyzability of cellulose without lignin inhibition, was 3.227 d, while those of the holocellulose fractions of five lignocellulosic substrates (I_k) were in the range of 1.270 d to 3.364 d (average of 2.242 d), which demonstrated remarkable suppression of holocellulose hydrolysis by lignin. Lignin inhibition index (LII) was proposed as an indicator to intuitively quantify and characterize the lignin inhibitory strength in a specific substrate. A series of factors with the potential to affect the LII were analyzed sequentially. This study provides an advanced understanding of the participation and behavior of lignin in the AD process.
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http://dx.doi.org/10.1016/j.biortech.2021.125204DOI Listing
April 2021

Dynamic low-coherence interferometry using a double Fizeau cavity.

Opt Lett 2021 May;46(9):2051-2054

The coexistence of anti-vibration and a common optical path is difficult to realize in dynamic Fizeau interferometry. To address this problem, we propose a dynamic low-coherence interferometry (DLI) using a double Fizeau cavity. The DLI method is a new optical model that creatively renders both surfaces of the RM to interfere with the test surface, utilizing a low-coherence source and optical path matching to construct the common-path -polarized Fizeau cavity (-FC) and carrier-frequency -polarized Fizeau cavity (-FC). The relative tilt phases of the -FC are calculated using the carrier frequency interferograms; then the final phase is retrieved with the relative tilt phases and -FC interferograms. The experimental results demonstrate that the DLI method can provide high-precision phase measurement in a vibration environment.
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http://dx.doi.org/10.1364/OL.416939DOI Listing
May 2021

Perinatal outcomes of neonates born from different endometrial preparation protocols after frozen embryo transfer: a retrospective cohort study.

BMC Pregnancy Childbirth 2021 Apr 29;21(1):341. Epub 2021 Apr 29.

International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, No.910, Hengshan Rd., Shanghai, 200030, China.

Background: Previous studies have focused on pregnancy outcomes after frozen embryo transfer (FET) performed using different endometrial preparation protocols. Few studies have evaluated the effect of endometrial preparation on pregnancy-related complications. This study was designed to explore the association between different endometrial preparation protocols and adverse obstetric and perinatal complications after FET.

Methods: We retrospectively included all FET cycles (n = 12,950) in our hospital between 2010 and 2017, and categorized them into three groups, natural cycles (NC), hormone replacement therapy (HRT) and ovarian stimulation (OS) protocols. Pregnancy-related complications and subsequent neonatal outcomes were compared among groups.

Results: Among all 12,950 FET cycles, the live birth rate was slightly lower for HRT cycles than for NC (HRT vs. NC: 28.15% vs. 31.16%, p < 0.001). The pregnancy loss rate was significantly higher in OS or HRT cycles than in NC (HRT vs. NC: 17.14% vs. 10.89%, p < 0.001; OS vs. NC: 16.44% vs. 10.89%, p = 0.001). Among 3864 women with live birth, preparing the endometrium using OS or HRT protocols increased the risk of preeclampsia, and intrahepatic cholestasis of pregnancy (ICP) in both singleton and multiple deliveries. Additionally, OS and HRT protocols increased the risk of low birth weight (LBW) and small for gestational age (SGA) in both singletons and multiples after FET.

Conclusion: Compared with HRT or OS protocols, preparing the endometrium with NC was associated with the decreased risk of pregnancy-related complications, as well as the decreased risk of LBW and SGA after FET.
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http://dx.doi.org/10.1186/s12884-021-03791-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086106PMC
April 2021

Transcriptional Regulation of Thrombin-Induced Endothelial VEGF Induction and Proangiogenic Response.

Cells 2021 Apr 15;10(4). Epub 2021 Apr 15.

Department of Nephrology and Internal Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.

Thrombin, the ligand of the protease-activated receptor 1 (PAR1), is a well-known stimulator of proangiogenic responses in vascular endothelial cells (ECs), which are mediated through the induction of vascular endothelial growth factor (VEGF). However, the transcriptional events underlying this thrombin-induced VEGF induction and angiogenic response are less well understood at present. As reported here, we conducted detailed promotor activation and signal transduction pathway studies in human microvascular ECs, to decipher the transcription factors and the intracellular signaling events underlying the thrombin and PAR-1-induced endothelial VEGF induction. We found that c-FOS is a key transcription factor controlling thrombin-induced EC VEGF synthesis and angiogenesis. Upon the binding and internalization of its G-protein-coupled PAR-1 receptor, thrombin triggers ERK1/2 signaling and activation of the nuclear AP-1/c-FOS transcription factor complex, which then leads to transcription, extracellular secretion, and concomitant proangiogenic responses of ECs. In conclusion, exposure of human microvascular ECs to thrombin triggers signaling through the PAR-1-ERK1/2-AP-1/c-FOS axis to control gene transcription and VEGF-induced angiogenesis. These observations offer a greater understanding of endothelial responses to thromboinflammation, which may help to interpret the results of clinical trials tackling the conditions associated with endothelial injury and thrombosis.
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http://dx.doi.org/10.3390/cells10040910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8071415PMC
April 2021

LncMyoD Promotes Skeletal Myogenesis and Regulates Skeletal Muscle Fiber-Type Composition by Sponging miR-370-3p.

Genes (Basel) 2021 Apr 17;12(4). Epub 2021 Apr 17.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China.

The development of skeletal muscle is a highly ordered and complex biological process. Increasing evidence has shown that noncoding RNAs, especially long-noncoding RNAs (lncRNAs) and microRNAs, play a vital role in the development of myogenic processes. In this study, we observed that lncMyoD regulates myogenesis and changes myofiber-type composition. miR-370-3p, which is directly targeted by lncMyoD, promoted myoblast proliferation and inhibited myoblast differentiation in the C2C12 cell line, which serves as a valuable model for studying muscle development. In addition, the inhibition of miR-370-3p promoted fast-twitch fiber transition. Further analysis indicated that acyl-Coenzyme A dehydrogenase, short/branched chain (ACADSB) is a target gene of miR-370-3p, which is also involved in myoblast differentiation and fiber-type transition. Furthermore, our data suggested that miR-370-3p was sponged by lncMyoD. In contrast with miR-370-3p, lncMyoD promoted fast-twitch fiber transition. Taken together, our results suggest that miR-370-3p regulates myoblast differentiation and muscle fiber transition and is sponged by lncMyoD.
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http://dx.doi.org/10.3390/genes12040589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8072939PMC
April 2021

Cross-Antigenicity between EV71 Sub-Genotypes: Implications for Vaccine Efficacy.

Viruses 2021 04 21;13(5). Epub 2021 Apr 21.

National Institutes for Food and Drug Control, Beijing 102600, China.

Enterovirus A-71 (EV71) is a global, highly contagkkious pathogen responsible for severe cases of hand-food-mouth-disease (HFMD). The use of vaccines eliciting cross neutralizing antibodies (NTAbs) against the different circulating EV71 sub-genotypes is important for preventing HFMD outbreaks. Here, we tested the cross-neutralizing activities induced by EV71 genotype/sub-genotype A, B0-B4, C1, C2, C4, and C5 viruses using rats. Differences were noted in the cross-neutralization of the 10 sub-genotypes tested but there were generally good levels of cross-neutralization except against genotype A virus, against which neutralization antibody titres (NTAb) where the lowest with NTAbs being the highest against sub-genotype B4. Moreover, NTAb responses induced by C4, B4, C1, and C2 viruses were homogenous, with values of maximum/minimum NTAb ratios (MAX/MIN) against all B and C viruses ranging between 4.0 and 6.0, whereas MAX/MIN values against B3 and A viruses were highly variable, 48.0 and 256.0, respectively. We then dissected the cross-neutralizing ability of sera from infants and children and rats immunized with C4 EV71 vaccines. Cross-neutralizing titers against the 10 sub-genotypes were good in both vaccinated infants and children and rats with the MAX/MIN ranging from 1.8-3.4 and 5.1-7.1, respectively, which were similar to those found in naturally infected patients (2.8). Therefore, we conclude that C4 EV71 vaccines can provide global protection to infants and children against HFMD caused by different sub-genotypes.
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http://dx.doi.org/10.3390/v13050720DOI Listing
April 2021

Predicting gene phenotype by multi-label multi-class model based on essential functional features.

Mol Genet Genomics 2021 Apr 29. Epub 2021 Apr 29.

School of Life Sciences, Shanghai University, Shanghai, 200444, People's Republic of China.

Phenotype is one of the most significant concepts in genetics, which is used to describe all the characteristics of a research object that can be observed. Considering that phenotype reflects the integrated features of genotype and environment factors, it is hard to define phenotype characteristics, even difficult to predict unknown phenotypes. Restricted by current biological techniques, it is still quite expensive and time-consuming to obtain sufficient structural information of large-scale phenotype-associated genes/proteins. Various bioinformatics methods have been presented to solve such problem, and researchers have confirmed the efficacy and prediction accuracy of functional network-based prediction. But general functional descriptions have highly complicated inner structures for phenotype prediction. To further address this issue and improve the efficacy of phenotype prediction on more than ten kinds of phenotypes, we first extract functional enrichment features from GO and KEGG, and then use node2vec to learn functional embedding features of genes from a gene-gene network. All these features are analyzed by some feature selection methods (Boruta, minimum redundancy maximum relevance) to generate a feature list. Such list is fed into the incremental feature selection, incorporating some multi-label classifiers built by RAkEL and some classic base classifiers, to build an optimum multi-label multi-class classification model for phenotype prediction. According to recent researches, our method has indeed identified many literature-supported genes/proteins and their associated phenotypes, and even some candidate genes with re-assigned new phenotypes, which provide a new computational tool for the accurate and effective phenotypic prediction.
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http://dx.doi.org/10.1007/s00438-021-01789-8DOI Listing
April 2021

Simultaneous Vascular Reconstruction and Cervical Anastomosis in McKeown Esophagectomy.

Front Surg 2021 8;8:646811. Epub 2021 Apr 8.

Department of Thoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.

A stomach was considered ineligible to be an ideal conduit conventionally if its right gastroepiploic artery (RGEA) were injured. However, both sufficient blood flow and good venous return are crucial to the success of reconstruction. And there lacks robust evidence regarding the surgical techniques of reconstructing RGEA and right gastroepiploic vein (RGEV) and performing cervical anastomosis with gastric conduit simultaneously. Herein, we summarized the key surgical techniques for simultaneous vascular reconstruction and gastric conduit anastomosis in McKeown esophagectomy.
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http://dx.doi.org/10.3389/fsurg.2021.646811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060638PMC
April 2021

The kynurenine derivative 3-HAA sensitizes hepatocellular carcinoma to sorafenib by upregulating phosphatases.

Theranostics 2021 3;11(12):6006-6018. Epub 2021 Apr 3.

Basic Medical Institute; Hongqiao International Institute of Medicine, Tongren Hospital; Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

: Sorafenib is the only FDA-approved first-line target drug for HCC patients. However, sorafenib merely confers 3-5 months of survival benefit with less than 30% of HCC patients sensitive to sorafenib therapy. Thus, it's necessary to develop a sensitizer for hepatocellular carcinoma (HCC) to sorafenib. : The principal component analysis, gene ontology, and KEGG analysis are utilized following RNA-sequencing. The mass spectrometry analysis following immunoprecipitation is performed to discover the phosphatase targets. Most importantly, both the cell line-derived xenograft (CDX) and the patient-derived xenograft (PDX) mouse model are used to determine the effect of 3-HAA on sorafenib-resistant HCC . : In nude mice carrying HCC xenograft, tumor growth is inhibited by sorafenib or 3-HAA alone. When used in combination, the treatment particularly prevents the xenograft from growing. Combined treatment also suppresses the growth of sorafenib-resistant (≥30mg/kg) PDXs. In a set of mechanistic experiments, we find enhanced AKT activation and decreased apoptotic cells in and acquired sorafenib-resistant HCC cells and tissues. 3-HAA decreases AKT phosphorylation and increases the apoptosis of HCC in both cultured cells and mouse xenografts by upregulation of phosphatases PPP1R15A/DUSP6. PPP1R15A/PPP1α directly reduces Akt phosphorylation while DUSP6 decreases Akt activity through inhibiting PDK1. The AKT activator abolishes 3-HAA inhibition of HCC growth and in mice. : This study demonstrates that 3-HAA sensitizes HCC cells to sorafenib by upregulation of phosphatases, suggesting it as a promising molecule for HCC therapy.
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http://dx.doi.org/10.7150/thno.59841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058709PMC
April 2021

MYC-Protein Arginine Methyltransferase 5 Axis Defines the Tumorigenesis and Immune Response in Hepatocellular Carcinoma.

Hepatology 2021 Apr 25. Epub 2021 Apr 25.

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths globally with poor outcome and limited therapeutic options. Although the MYC oncogene is frequently dysregulated in HCC, it is thought to be undruggable. Thus, the current study aimed to identify the critical downstream metabolic network of MYC and develop new therapies for MYC-driven HCC. Liver cancer was induced in mice with hepatocyte-specific disruption of Myc and control mice by administration of diethylnitrosoamine (DEN). Liquid chromatography coupled with mass spectrometry-based metabolomic analyses revealed that urinary dimethylarginine, especially symmetric dimethylarginine (SDMA), was increased in the HCC mouse model in a MYC-dependent manner. Analyses of human samples demonstrated a similar induction of SDMA in the urines from HCC patients. Mechanistically, Prmt5, encoding protein arginine methyltransferase 5, which catalyzes SDMA formation from arginine, was highly induced in HCC and identified as a direct MYC target gene. Moreover, GSK3326595, a PRMT5 inhibitor, suppressed the growth of liver tumors in human MYC-overexpressing transgenic mice that spontaneously develop HCC. Inhibition of PRMT5 exhibited anti-proliferative activity via upregulation of the tumor suppressor gene Cdkn1b/p27. In addition, GSK3326595 induced lymphocyte infiltration and MHC II expression, which might contribute to the enhanced anti-tumor immune response. Combination of GSK3326595 with anti-PD-1 immune checkpoint therapy (ICT) improved therapeutic efficacy in HCC. This study revealed that PRMT5 is an epigenetic executer of MYC leading to repression of the transcriptional regulation of downstream genes that promote hepatocellular carcinogenesis, highlights a mechanism-based therapeutic strategy for MYC-driven HCC via PRMT5 inhibition through synergistically suppressed proliferation and enhanced anti-tumor immunity, and finally provides an opportunity to mitigate the resistance of "immune-cold" tumor to ICT.
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http://dx.doi.org/10.1002/hep.31864DOI Listing
April 2021

Non-coding RNA: insights into the mechanism of methamphetamine neurotoxicity.

Mol Cell Biochem 2021 Apr 25. Epub 2021 Apr 25.

Department of Clinical Pharmacology, School of Pharmacy, China Medical University, No.77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, People's Republic of China.

Chronic exposure of the methamphetamine has been shown to lead to neurotoxicity in rodents and humans. The manifestations of methamphetamine neurotoxicity include methamphetamine use disorder, methamphetamine abuse, methamphetamine addiction and methamphetamine behavioral sensitization. Repeated use of methamphetamine can cause methamphetamine use disorder. The abuse and addiction of methamphetamine are growing epidemic worldwide. Repeated intermittent exposure to methamphetamine can cause behavioral sensitization. In addition, many studies have shown that changes in the expression of non-coding RNA in the ventral tegmental area and nucleus accumbens will affect the behavioral effects of methamphetamine. Non-coding RNA plays an important role in the behavioral effects of methamphetamine. Therefore, it is important to study the relationship between methamphetamine and non-coding RNA. The purpose of this review is to study the non-coding RNA associated with methamphetamine neurotoxicity to search for the possible therapeutic target of the methamphetamine neurotoxicity.
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http://dx.doi.org/10.1007/s11010-021-04160-yDOI Listing
April 2021

Soil fungal diversity and community assembly: affected by island size or type?

FEMS Microbiol Ecol 2021 May;97(5)

State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.

Fungi have a huge biodiversity and play important roles in soil biogeochemical cycling in island ecosystems. Although island biogeography has been widely studied for macroorganisms, fungal community assembly in true islands and its relationship with island area are less documented. We examined soil fungal communities in 18 oceanic islands of two types (eight non-coral islands and 10 coral islands) using the Illumina MiSeq sequencing technique. Our results showed that fungal α-diversity (species richness) was substantially different among the oceanic islands, with a higher value in non-coral islands than in coral islands. Fungal α-diversity was significantly affected by soil potassium and magnesium (Mg) and plant communities in non-coral islands, whereas only soil Mg significantly affected it in coral islands. Soil fungal community composition was significantly different in the non-coral and coral islands and was influenced by soil property, plant community and spatial distance. The ecological stochasticity model showed that the fungal community assembly was mainly governed by deterministic processes regardless of island type. Fungal β-diversity, but not α-diversity, increased significantly with increasing island area. These findings have implications for the better prediction of soil fungal community dynamics in island systems and biodiversity conservation in fragmented habitats.
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http://dx.doi.org/10.1093/femsec/fiab062DOI Listing
May 2021