Publications by authors named "Hong Ma"

1,085 Publications

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Association of central obesity with hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy.

Aliment Pharmacol Ther 2021 Jun 22. Epub 2021 Jun 22.

Guangzhou, China.

Background: Obesity is typically associated with metabolic dysfunction, but its impact on hepatocellular carcinoma (HCC) remains unclear in patients with chronic hepatitis B (CHB).

Aim: To study the effect of obesity on HCC development in patients with CHB receiving antiviral therapy.

Methods: We included patients from a Chinese multicentre, prospective, observational, treated CHB cohort in this study. General obesity was evaluated by body-mass index (BMI). Central obesity was evaluated by waist circumference, waist-to-hip ratio and waist-to-height ratio.

Results: A total of 5754 nucleos(t)ide analogue treated patients were enrolled in the analysis. The 5-year cumulative incidence of HCC was 2.9%. Waist-to-height ratio performed better in predicting HCC development than BMI, waist circumference or waist-to-hip ratio. Patients with central obesity (defined as waist-to-height ratio >0.5) had significantly higher 5-year incidence of HCC than those without central obesity in the overall population (3.9% vs 2.1%, hazard ratio [HR]: 2.06, P = 0.0001) and 745 propensity score matched pairs (4.7% vs 2.3%, HR: 2.04, P = 0.026), respectively. Besides cirrhosis status and aMAP HCC risk score, central obesity was also independently associated with HCC risk (HR: 1.63, P = 0.013). Waist-to-height ratio gain within 1 year was associated with a significantly higher HCC risk with an adjusted HR value of 1.88 (95% confidence interval: 1.12-3.13, P = 0.017).

Conclusions: Central obesity, evaluated by the waist-to-height ratio, was associated with a twofold increase in HCC risk among CHB patients receiving antiviral treatment, highlighting the important role of abnormal metabolic function in the progression of liver disease.
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http://dx.doi.org/10.1111/apt.16469DOI Listing
June 2021

TBX20 Contributes to Balancing the Differentiation of Perivascular Adipose-Derived Stem Cells to Vascular Lineages and Neointimal Hyperplasia.

Front Cell Dev Biol 2021 2;9:662704. Epub 2021 Jun 2.

Department of Cardiology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Background: Perivascular adipose-derived stem cells (PVASCs) can contribute to vascular remodeling, which are also capable of differentiating into multiple cell lineages. The present study aims to investigate the mechanism of PVASC differentiation toward smooth muscle cells (SMCs) and endothelial cells (ECs) as well as its function in neointimal hyperplasia.

Methods: Single-cell sequencing and bulk mRNA sequencing were applied for searching key genes in PVASC regarding its role in vascular remodeling. PVASCs were induced to differentiate toward SMCs and ECs , which was quantitatively evaluated using immunofluorescence, quantitative real-time PCR (QPCR), and Western blot. Lentivirus transfections were performed in PVASCs to knock down or overexpress TBX20. , PVASCs transfected with lentivirus were transplanted around the guidewire injured femoral artery. Hematoxylin-eosin (H&E) staining was performed to examine their effects on neointimal hyperplasia.

Results: Bulk mRNA sequencing and single-cell sequencing revealed a unique expression of TBX20 in PVASCs. TBX20 expression markedly decreased during smooth muscle differentiation while it increased during endothelial differentiation of PVASCs. TBX20 knockdown resulted in the upregulation of SMC-specific marker expression and activated Smad2/3 signaling, while inhibiting endothelial differentiation. In contrast, TBX20 overexpression repressed the differentiation of PVASCs toward smooth muscle cells but promoted endothelial differentiation . Transplantation of PVASCs transfected with TBX20 overexpression lentivirus inhibited neointimal hyperplasia in a murine femoral artery guidewire injury model. On the contrary, neointimal hyperplasia significantly increased in the TBX20 knockdown group.

Conclusion: A subpopulation of PVASCs uniquely expressed TBX20. TBX20 could regulate SMC and EC differentiation of PVASCs . Transplantation of PVASCs after vascular injury suggested that PVASCs participated in neointimal hyperplasia via TBX20.
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http://dx.doi.org/10.3389/fcell.2021.662704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8206642PMC
June 2021

Impact of corticosteroid use on outcomes of non-small-cell lung cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

J Clin Pharm Ther 2021 Jun 17. Epub 2021 Jun 17.

Department of Oncology and Hematology, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, China.

What Is Known And Objective: Administration of corticosteroids to immune checkpoint inhibitors (ICI)-treated patients has raised concerns due to doubts about ICIs' efficacy under those conditions. Hence, we reviewed studies comparing overall and progression-free survival (OS and PFS) outcomes in patients with non-small-cell lung carcinoma (NSCLC) treated with ICI and either with or without corticosteroids for any reason.

Methods: We searched the PubMed Central, Cochrane library, EMBASE and MEDLINE databases from inception until February 2021 for relevant publications. We used the Newcastle-Ottawa scale to assess the quality of the identified studies. We used the published data to carry out a meta-analysis with a random-effects model and report pooled odds ratios (ORs) with 95% confidence intervals (CIs).

Results: We included data from 14 studies with 5461 participants in the meta-analysis. Most studies were retrospective in nature and of low quality, and most of them were conducted in the USA and in European countries. Nivolumab is the most common ICI used in the included studies followed by pembrolizumab. We found that patients using corticosteroids had reduced OSs (pooled HR, 1.82; 95% CI, 1.51-2.18) and PFSs (pooled HR, 1.69; 95% CI, 1.41-2.04) than the patients not using corticosteroids. We identified significant heterogeneity and publication bias for both the outcomes. However, the sensitivity analysis revealed that the estimates were robust to the individual study effects.

What Is New And Conclusion: Our findings suggest that corticosteroids significantly reduce the OS and PFS of patients with NSCLC under ICI therapy. Hence, clinicians and oncologists should consider this information when prescribing corticosteroids for this target population.
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http://dx.doi.org/10.1111/jcpt.13469DOI Listing
June 2021

Photon-recycling effect in perovskites for photovoltaic applications: a Monte Carlo study.

Opt Lett 2021 Jun;46(12):2988-2991

Photon recycling has been shown to play an important role in the optoelectronic properties and device performance of perovskite solar cells recently. However, there lacks an analytical method to accurately predict the dynamics of charge carriers and photons and the device performance with photon recycling due to the complexity of multiple electron-photon conversion processes involved in photon recycling. We propose a model based on the Monte Carlo simulation method that combines charge carrier diffusion and photon radiation transport to analyze the effects of photon recycling on electron-photon dynamics and device performance of perovskite solar cells. We show that the carrier lifetime can be significantly boosted by photon recycling in the radiative limit, which yields a 37 meV increase in the open-circuit voltage for a 500 nm thick perovskite solar cell. Our results provide insights for the working mechanisms of perovskite solar cells, and the new model can be further applied to other types of solar cells with photon recycling.
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http://dx.doi.org/10.1364/OL.427600DOI Listing
June 2021

Hydrogen Binding Initiated Activation of O-H Bonds on a Nitrogen-Doped Surface for Catalytic Oxidation of Biomass Hydroxyl Compounds.

Angew Chem Int Ed Engl 2021 Jun 14. Epub 2021 Jun 14.

Chinese Academy of Sciences, Dalian Institute of Chemical Physics, 457 Zhongshan Road, 116023, Dalian, CHINA.

Hydrogen binding of molecules on specific solid surface is an attractive interaction that can be employed as driving force for chemical bond activation, material directed assembly, protein protection, etc. However, the lack of quantitative characterization method for hydrogen bonds (HBs) on surface seriously limits its application. Herein, we measured the standard Gibbs free energy change (ΔG 0 ) of surface HBs using NMR technique. HBs accepting ability of surface was investigated in term of comparing ΔG 0 values by employing model biomass platform 5-hydroxymethylfurfural on a series of Co-N-C-n catalysts with electron-rich doped-nitrogen contents adjusted. Reducing the ΔG 0 effectively improves HBs accepting ability of the nitrogen-doped surface, and promotes the O-H bonds selectively initiated activation in the oxidation of 5-hydroxymethylfurfural. As a result, the reaction kinetics is accelerated and the rate constant is significantly increased. In addition to excellent catalytic performance, the turnover frequency (TOF) value for this oxidation is extremely higher than the reported non-noble metal catalysts.
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http://dx.doi.org/10.1002/anie.202103604DOI Listing
June 2021

Chinese mental health workers' family-focused practices: a cross-sectional survey.

BMC Health Serv Res 2021 Jun 9;21(1):569. Epub 2021 Jun 9.

Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.

Background: Mental disorders impose heavy burdens on patients' families and children. It is imperative to provide family-focused services to avoid adverse effects from mental disorders on patients' families and children. However, implementing such services requires a great deal of involvement of mental health workers. This study investigated the attitudes, knowledge, skills, and practices in respect to family-focused practices (FFP) in a sample of Chinese mental health workers.

Methods: A cross-sectional study design was employed to examine the attitudes, knowledge, skills, and practices of a convenience sample of Chinese mental health workers in respect to FFP, using the Chinese version of the Family-Focused Mental Health Practice Questionnaire (FFMHPQ).

Results: In total, 515 mental health workers participated in our study, including 213 psychiatrists, 269 psychiatric nurses, and 34 allied mental health professionals (20 clinical psychologists, 9 mental health social workers, and 4 occupational therapists). Compared with psychiatric nurses, psychiatrists and allied mental health professionals provided more support for families and children of patients with mental illness and were more willing to receive further training in FFP. However, there were no significant differences on knowledge, skills, and confidence across different profession types. After adjusting for demographic and occupational variables, previous training in FFP was positively associated with mental health workers' knowledge, skills, and confidence about FFP, but not actual support to families and children.

Conclusions: Professional differences on FFP exist in Chinese mental health workers. Training is needed to engage psychiatrists and other allied workforce in dissemination and implementation of FFP in China.
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http://dx.doi.org/10.1186/s12913-021-06572-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191031PMC
June 2021

Epstein-Barr virus-associated intracranial myopericytoma in a child: case report and review of literature.

Childs Nerv Syst 2021 Jun 8. Epub 2021 Jun 8.

Division of Neurosurgery, Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines.

Background: Myopericytomas are benign soft tissue tumors which are rarely found as intracranial masses.

Methods: A review of SCOPUS and PubMed databases for case reports and case series was done for patients with intracranial myopericytomas. Data on demographics, clinical features, imaging, surgical management employed, and outcomes were collected.

Results: We found a total of 9 cases in the literature and we describe an additional case from our own experience. The mean age at presentation was 50.1 years (32-64 years), with a female predominance. Most tumors were in the posterior fossa and were multifocal in AIDS patients. The most common clinical manifestations were visual disturbances, headaches, and vomiting. An association with EBV was reported in two cases and was also found in our own case. Gross total excision and even subtotal excision were definitive therapies with no recurrences reported with a mean follow-up of 22.7 months. Our case is the first EBV-associated intracranial myopericytoma in a child.

Conclusion: Intracranial myopericytomas are rare; some have an association with EBV and immunodeficient states. Surgery is the only necessary treatment and outcomes are generally favorable for these benign neoplasms.
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http://dx.doi.org/10.1007/s00381-021-05220-wDOI Listing
June 2021

Construction and External Validation of a Ferroptosis-Related Gene Signature of Predictive Value for the Overall Survival in Bladder Cancer.

Front Mol Biosci 2021 21;8:675651. Epub 2021 May 21.

Department of Urology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.

To identify whether ferroptosis-related genes play predictive roles in bladder cancer patients and to develop a ferroptosis-related gene signature to predict overall survival outcomes. We downloaded the mRNA expression files and clinical data of 256 bladder samples (188 bladder tumour and 68 nontumour samples) from the GEO database and 430 bladder samples (411 bladder tumour and 19 nontumour samples) from the TCGA database. A multigene signature based on prognostic ferroptosis-related genes was constructed by least absolute shrinkage and selection operator Cox regression analysis in the GEO cohort. The TCGA cohort was used to validate the ferroptosis-related gene signature. Next, functional enrichment analysis, including both Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses, was performed to elucidate the mechanism underlying the signature. The ssGSEA scores of 16 immune cells and 13 immune-related pathway activities between the high-risk and low-risk groups were also analysed in our study. Thirty-three (67.3%) ferroptosis-related genes were differentially expressed between bladder tumour samples and nontumour samples in the GEO cohort. The intersection of prognostic ferroptosis-related genes and differentially expressed genes identified four prognostic targets, including ALOX5, FANCD2, HMGCR and FADS2. The least absolute shrinkage and selection operator Cox regression successfully built a 4-gene signature: risk score value = e (each gene's normalized expression * each gene's coefficient). Univariate and multivariate Cox regression analyses were performed in both the GEO and TCGA cohorts to test the independent prognostic value of the 4-gene risk signature. Multivariate Cox regression analysis in the GEO cohort identified age ( < 0.001), grade ( = 0.129) and risk score ( = 0.016) as independent prognostic predictors for overall survival. Multivariate Cox regression analysis in the TCGA cohort also identified age ( = 0.002), stage ( < 0.001) and risk score ( = 0.006) as independent prognostic predictors for overall survival. The type II IFN response was determined to be significantly weakened in the high-risk group in both the GEO and TCGA cohorts. We successfully built a ferroptosis-related gene signature of significant predictive value for bladder cancer. These results suggest a novel research direction for targeted therapy of bladder cancer in the future.
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http://dx.doi.org/10.3389/fmolb.2021.675651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175978PMC
May 2021

A multicenter survey of perioperative anxiety in China: Pre- and postoperative associations.

J Psychosom Res 2021 May 19;147:110528. Epub 2021 May 19.

Department of Anesthesiology, Pain and Sleep Medicine, Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine, Chinese Academy of Sciences, Beijing, China; School of Anesthesiology, Weifang Medical University, Weifang, Shangdong, China. Electronic address:

Objectives: To describe patient characteristics associated with preoperative anxiety and subsequently assess the relationship between preoperative anxiety and postoperative anxiety, pain, sleep quality, nausea and vomiting.

Methods: The study collected data from patients undergoing elective operation from 12 hospitals in China. The State-Trait Anxiety Inventory (STAI) and the Athens Insomnia Scale (AIS) were used to assess anxiety and sleep quality before surgery. Evaluations of anxiety, pain, sleep quality, nausea and vomiting were quantified using the Visual Analogue Scale on postoperative days 1 and 2.

Results: Data from 997 patients were analyzed. Preoperatively, 258 (25.9%) patients had high anxiety (STAI-State>44). Multivariate analyses showed a significant relationship between high anxiety and female gender (OR: 1.66, 95% CI: 1.08-2.57, p = 0.02), highly invasive surgery (OR: 2.29, 95% CI: 1.29-4.06, p = 0.005), higher trait anxiety (OR: 1.24, 95% CI: 1.20-1.28, p < 0.001) and insomnia (AIS ≥ 6, OR: 1.79, 95% CI: 1.17-2.76, p = 0.008). Preoperative anxiety demonstrated a negative correlation with postoperative anxiety following highly invasive surgery; this became a positive relationship following less invasive surgery. Preoperative anxiety was also positively related to postoperative pain and poor sleep quality. The correlation between preoperative anxiety and postoperative nausea and vomiting was not statistically significant.

Conclusion: Female gender, highly invasive surgery, higher trait anxiety and insomnia are independent risk factors for high preoperative anxiety. Surgical invasiveness influences association between pre- and postoperative anxiety. Higher preoperative anxiety is related to poorer sleep quality and more severe pain postoperatively.
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http://dx.doi.org/10.1016/j.jpsychores.2021.110528DOI Listing
May 2021

Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis.

Mol Metab 2021 May 18;53:101257. Epub 2021 May 18.

Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, China. Electronic address:

Background: Phosphoenolpyruvate carboxykinase (PCK) has been almost exclusively recognized as a critical enzyme in gluconeogenesis, especially in the liver and kidney. Accumulating evidence has shown that the enhanced activity of PCK leads to increased glucose output and exacerbation of diabetes, whereas the defects of PCK result in lethal hypoglycemia. Genetic mutations or polymorphisms are reported to be related to the onset and progression of diabetes in humans.

Scope Of Review: Recent studies revealed that the PCK pathway is more complex than just gluconeogenesis, depending on the health or disease condition. Dysregulation of PCK may contribute to the development of obesity, cardiac hypertrophy, stroke, and cancer. Moreover, a regulatory network with multiple layers, from epigenetic regulation, transcription regulation, to posttranscription regulation, precisely tunes the expression of PCK. Deciphering the molecular basis that regulates PCK may pave the way for developing practical strategies to treat metabolic dysfunction.

Major Conclusions: In this review, we summarize the metabolic and non-metabolic roles of the PCK enzyme in cells, especially beyond gluconeogenesis. We highlight the distinct functions of PCK isoforms (PCK1 and PCK2), depict a detailed network regulating PCK's expression, and discuss its clinical relevance. We also discuss the therapeutic potential targeting PCK and the future direction that is highly in need to better understand PCK-mediated signaling under diverse conditions.
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http://dx.doi.org/10.1016/j.molmet.2021.101257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190478PMC
May 2021

Detection of Hepatitis B Virus M204V Mutation Quantitatively via Real-time PCR.

J Clin Transl Hepatol 2021 Apr 16;9(2):143-148. Epub 2021 Mar 16.

Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center of Digestive Diseases, Beijing, China.

Background And Aims: Drug-resistant DNA mutations of the hepatitis B virus (HBV) affect treatment response in chronic hepatitis B patients. We have established a new, sensitive, specific, accurate and convenient real-time PCR method to detect HBV mutations quantitatively.

Methods: Blood samples were collected from patients showing viral breakthrough, primary nonresponse, or poor response during treatment, and mutations were detected via direct sequencing to assess our method. A plasmid containing the M204V mutation was synthesized and standard curves plotted.

Results: The determination coefficient for linear correlation between Ct and log plasmid copy numbers was 0.996, where Ct value was -3.723log (DNA concentration) +48.647. Coefficients of variation indicated good reproducibility. Correctness was within tolerable bias. Limit of detection was 10 copies/mL. Specificity, accuracy, positive predictive value and negative predictive value were 92.86%, 100%, 96.88%, 100% and 94.74%, respectively.

Conclusions: These results show that our method can be used to detect HBV M204V mutations with the advantages of sensitivity, specificity and efficiency, providing a new choice for monitoring drug resistance.
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http://dx.doi.org/10.14218/JCTH.2020.00118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111100PMC
April 2021

Posttraumatic stress disorder and professional burnout among local government staff seven years after the Wenchuan earthquake in China: A longitudinal study.

Asian J Psychiatr 2021 Jul 10;61:102689. Epub 2021 May 10.

Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China.

Although local government staff are crucial in post-quake reconstruction, their long-term psychological and professional consequences remain unclear. This longitudinal study investigated changes of posttraumatic stress disorder (PTSD) and professional burnout over seven years, and their underlying relationship. The study assessed 250 staff at one year (T) after the earthquake, and 162 (64.8 %) were followed up at seven years (T). PTSD and professional burnout were assessed with the Short Screening Scale for DSM-IV PTSD and the burnout subscale of Professional Quality of Life Scale (ProQOL), respectively, at both time points. Longitudinal changes in PTSD and burnout were examined and cross-lagged panel analyses were conducted to test the relationship between PTSD and burnout. The rates of positive cases of PTSD screening were 23.2 % at T and 11.1 % at T. The percentages of moderate burnout were 61.7 % at T and 23.5 % at T. Scores of PTSD (z = -5.70, p < 0.001) and burnout (t = 10.07, p < 0.001) from T to T decreased. The cross-lagged analysis indicated that burnout at T predicted PTSD at T (β = 0.19, p = 0.025). In conclusion, the Wenchuan earthquake has long-lasting negative effects on local government staff, although they can recover over time. Interventions to reduce professional burnout after disaster may does be beneficial to decrease the risk of PTSD in the long run.
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http://dx.doi.org/10.1016/j.ajp.2021.102689DOI Listing
July 2021

Analysis of paralogs in target enrichment data pinpoints multiple ancient polyploidy events in Alchemilla s.l. (Rosaceae).

Syst Biol 2021 May 12. Epub 2021 May 12.

Department of Plant and Microbial Biology, University of Minnesota-Twin Cities, 1445 Gortner Avenue, St. Paul, MN 55108, USA.

Target enrichment is becoming increasingly popular for phylogenomic studies. Although baits for enrichment are typically designed to target single-copy genes, paralogs are often recovered with increased sequencing depth, sometimes from a significant proportion of loci, especially in groups experiencing whole-genome duplication (WGD) events. Common approaches for processing paralogs in target enrichment data sets include random selection, manual pruning, and mainly, the removal of entire genes that show any evidence of paralogy. These approaches are prone to errors in orthology inference or removing large numbers of genes. By removing entire genes, valuable information that could be used to detect and place WGD events is discarded. Here we used an automated approach for orthology inference in a target enrichment data set of 68 species of Alchemilla s.l. (Rosaceae), a widely distributed clade of plants primarily from temperate climate regions. Previous molecular phylogenetic studies and chromosome numbers both suggested ancient WGDs in the group. However, both the phylogenetic location and putative parental lineages of these WGD events remain unknown. By taking paralogs into consideration and inferring orthologs from target enrichment data, we identified four nodes in the backbone of Alchemilla s.l. with an elevated proportion of gene duplication. Furthermore, using a gene-tree reconciliation approach we established the autopolyploid origin of the entire Alchemilla s.l. and the nested allopolyploid origin of four major clades within the group. Here we showed the utility of automated tree-based orthology inference methods, previously designed for genomic or transcriptomic data sets, to study complex scenarios of polyploidy and reticulate evolution from target enrichment data sets.
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http://dx.doi.org/10.1093/sysbio/syab032DOI Listing
May 2021

Role of nucleus accumbens microRNA-181a and MeCP2 in incubation of heroin craving in male rats.

Psychopharmacology (Berl) 2021 May 1. Epub 2021 May 1.

Laboratory of Behavioral Neuroscience, Ningbo Kangning Hospital, Ningbo Institute of Microcirculation and Henbane, School of Medicine, Ningbo University, Ningbo, 315010, Zhejiang, People's Republic of China.

Rationale: Epigenetic regulation has been implicated in the incubation of drug craving (the time-dependent increase in drug seeking after prolonged withdrawal from drug self-administration). There is little information available on the role of microRNAs in incubation of heroin craving.

Objective: This study aimed to investigate the roles and mechanisms of miR-181a and methyl CpG binding protein 2 (MeCP2) in the nucleus accumbens (NAc) in incubation of heroin seeking.

Methods: MiRNA sequencing was used to predict potential miRNAs, and miRNA profiles were performed in the NAc after 1 day or 14 days after withdrawal from heroin self-administration. Following 14 days of heroin self-administration, rats were injected of lentiviral vectors into the NAc and evaluated for the effects of overexpression of miR-181a or knockdown of MeCP2 on non-reinforced heroin seeking after 14 withdrawal days.

Results: Lever presses during the heroin-seeking tests were higher after 14 withdrawal days than after 1 day (incubation of heroin craving). miR-181a expression in NAc was lower after 14 withdrawal days than after 1 day, and meCP2 expression in NAc was higher after 14 days than after 1 day. Luciferase activity assay showed that the 3'UTR of MeCP2 is directly regulated by miR-181a. Overexpression of miR-181a in NAc decreased heroin seeking after 14 withdrawal days and decreased MeCP2 mRNA and protein expression. Knockdown of MeCP2 expression in NAc by LV-siRNA-MeCP2 also decreased heroin seeking after 14 withdrawal days.

Conclusions: Results indicate that incubation of heroin craving is mediated in part by time-dependent decreases in NAc miR181a expression that leads to time-dependent increases in MeCP2 expression. Our data suggest that NAc miR-181a and MeCP2 contribute to incubation of heroin craving.
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http://dx.doi.org/10.1007/s00213-021-05854-3DOI Listing
May 2021

Zoledronic acid modulates osteoclast apoptosis through activation of the NF-κB signaling pathway in ovariectomized rats.

Exp Biol Med (Maywood) 2021 Apr 29:15353702211011052. Epub 2021 Apr 29.

Department of Pathology, Guizhou Medical University School of Medicine, Guizhou 550004, P.R. China.

Bone mass loss (osteoporosis) seen in postmenopausal women is an adverse factor for implant denture. Using an ovariectomized rat model, we studied the mechanism of estrogen-deficiency-caused bone loss and the therapeutic effect of Zoledronic acid. We observed that ovariectomized-caused resorption of bone tissue in the mandible was evident at four weeks and had not fully recovered by 12 weeks post-ovariectomized compared with the sham-operated controls. Further evaluation with a TUNEL assay showed ovariectomized enhanced apoptosis of osteoblasts but inhibited apoptosis of osteoclasts in the mandible. Zoledronic acid given subcutaneously as a single low dose was shown to counteract both of these ovariectomized effects. Immunohistochemical staining showed that ovariectomized induced the protein levels of RANKL and the 65-kD subunit of the NF-κB complex mainly in osteoclasts, as confirmed by staining for TRAP, a marker for osteoclasts, whereas zoledronic acid inhibited these inductions. Western blotting showed that the levels of RANKL, p65, as well as the phosphorylated form of p65, and IκB-α were all higher in the ovariectomized group than in the sham and ovariectomized + zoledronic acid groups at both the 4th- and 12th-week time points in the mandible. These data collectively suggest that ovariectomized causes bone mass loss by enhancing apoptosis of osteoblasts and inhibiting apoptosis of osteoclasts. In osteoclasts, these cellular effects may be achieved by activating RANKL-NF-κB signalling. Moreover, zoledronic acid elicits its therapeutic effects in the mandible by counteracting these cellular and molecular consequences of ovariectomized.
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http://dx.doi.org/10.1177/15353702211011052DOI Listing
April 2021

Glutamine metabolism: from proliferating cells to cardiomyocytes.

Metabolism 2021 Apr 24;121:154778. Epub 2021 Apr 24.

Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China. Electronic address:

Glutamine is a major energy source for rapidly dividing cells, such as hematopoietic stem cells and cancer cells. Reliance on glutamine is therefore regarded as a metabolic hallmark of proliferating cells. Moreover, reprogramming glutamine metabolism by various factors, including tissue type, microenvironment, pro-oncogenes, and tumor suppressor genes, can facilitate stem cell fate decisions, tumor recurrence, and drug resistance. However, the significance of glutamine metabolism in cardiomyocytes, an end-differentiated cell type, is not fully understood. Existing evidence suggests important roles of glutamine metabolism in the development of cardiovascular diseases. In this review, we have focused on glutaminolysis and its regulatory network in proliferating cells. We have summarized current findings about the role of glutamine utilization in cardiomyocytes and have discussed possibilities of targeting glutamine metabolism for the treatment of cardiovascular diseases.
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http://dx.doi.org/10.1016/j.metabol.2021.154778DOI Listing
April 2021

Single cell dual-omics reveals the transcriptomic and epigenomic diversity of cardiac non-myocytes.

Cardiovasc Res 2021 Apr 11. Epub 2021 Apr 11.

Department of Pathology and Laboratory Medicine.

Aims: The precise cellular identity and molecular features of non-myocytes (nonCM) in a mammalian heart at a single cell level remain elusive. Depiction of epigenetic landscape with transcriptomic signatures using the latest single-cell multi-omics has the potential to unravel the molecular programs underlying the cellular diversity of cardiac non-myocytes. Here, we characterized the molecular and cellular features of cardiac nonCM populations in the adult murine heart at the single cell level.

Methods And Results: Through single-cell dual omics analysis, we mapped the epigenetic landscapes, characterized the transcriptomic profiles and delineated the molecular signatures of cardiac nonCMs in the adult murine heart. Distinct cis-regulatory elements and trans-acting factors for the individual major nonCM cell types (endothelial cells, fibroblast, pericytes and immune cells) were identified. In particular, unbiased sub-clustering and functional annotation of cardiac fibroblasts (FB) revealed extensive FB heterogeneity and identified FB subtypes with functional states related to cellular response to stimuli, cytoskeleton organization and immune regulation, respectively. We further explored the function of marker genes Hsd11b1 and Gfpt2 that label major FB sub-populations and determined the distribution of Hsd11b1+ and Gfp2+ FBs in murine healthy and diseased hearts.

Conclusions: In summary, we characterized the nonCM cellular identity at the transcriptome and epigenome levels using single-cell omics approaches and discovered previously unrecognized cardiac fibroblast subpopulations with unique functional states.

Translational Perspective: Our research identified discrete cell types of nonCM in the heart and differentially expressed genes with regulatory factors. Unveiling the heterogeneity of nonCMs and molecular signatures of each cell type or subtypes allows for study, precise capture and manipulation of specific cell type(s) in heart and will provide insights into the development of therapeutics for cardiovascular diseases.
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http://dx.doi.org/10.1093/cvr/cvab134DOI Listing
April 2021

A longitudinal study on emotional distress among local government staff seven years after the 2008 Wenchuan earthquake in China.

BMC Public Health 2021 04 9;21(1):702. Epub 2021 Apr 9.

Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Haidian District Huayuan North Road No. 51, Beijing, 100191, China.

Background: The current study examined the change in local government staff's emotional distress over 7 years after the 2008 Wenchuan earthquake, and the influence of earthquake exposure and professional quality of life (ProQOL) on emotional distress.

Methods: This longitudinal study assessed 250 participants at 1 year after the earthquake; 162 (64.8%) were followed up at 7 years. Emotional distress was assessed with the Self-Reporting Questionnaire (SRQ) at both time points. We assessed ProQOL, including compassion satisfaction, burnout, and secondary traumatic stress, and earthquake exposure at 1 year. Wilcoxon signed-rank tests were performed to test longitudinal changes in emotional distress. Hierarchical multiple regression was conducted to examine the effect of earthquake exposure and ProQOL.

Results: The positive screening rate of emotional distress (SRQ ≥ 8) was 37.6 and 15.4% at one and 7 years, respectively. Emotional distress scores declined over time (p < 0.001). Earthquake exposure and ProQOL predicted one-year (ps < 0.05) but not seven-year emotional distress, whereas burnout predicted both one-year (p = 0.018) and seven-year (p = 0.047) emotional distress.

Conclusions: Although emotional distress can recover over time, it persists even 7 years later. Actions to reduce burnout during the early stage of post-disaster rescue have long-term benefits to staff's psychological outcomes.
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http://dx.doi.org/10.1186/s12889-021-10726-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033268PMC
April 2021

Dipeptidyl-peptidase 3 protects oxygen-glucose deprivation/reoxygenation-injured hippocampal neurons by suppressing apoptosis, oxidative stress and inflammation via modulation of Keap1/Nrf2 signaling.

Int Immunopharmacol 2021 Jul 31;96:107595. Epub 2021 Mar 31.

Anesthesiology Department, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China. Electronic address:

Dipeptidyl-peptidase 3 (DPP3) plays a key role in regulating apoptosis, oxidative stress and inflammation under various pathological conditions, however, whether DPP3 regulates apoptosis and oxidative stress in neurons undergoing cerebral ischemia/reperfusion injury has not yet been well studied. The goals of this work were to evaluate the role of DPP3 in the regulation of oxygen-glucose deprivation/reoxygenation (OGD/R)-induced apoptosis, oxidative stress and inflammation in HT22 hippocampal neurons. Here, we showed that DPP3 expression was elevated in response to OGD/R in neurons. Knockdown of DPP3 exacerbated OGD/R-induced apoptosis, oxidative stress and inflammation, whilst up-regulation of DPP3 alleviated OGD/R-induced apoptosis, oxidative stress and inflammation in HT22 neurons. Further results revealed that DPP3 enhanced the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and promoted transcriptional activity of the anti-oxidant response element (ARE). Additionally, DPP3 was shown to regulate Nrf2/ARE activation in a kelch-like ECH-associated protein 1 (Keap1)-dependent manner. Notably, inhibition of Nrf2 markedly reversed the DPP3-mediated neuroprotective effects against OGD/R injury. Taken together, these findings demonstrate that DPP3 exerts a neuroprotective role in OGD/R-injured neurons by suppressing neuronal apoptosis, oxidative stress and inflammation via modulation of Keap1/Nrf2 signaling. This work suggests DPP3 as a potential target for providing neuroprotective effects during cerebral ischemia/reperfusion injury.
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http://dx.doi.org/10.1016/j.intimp.2021.107595DOI Listing
July 2021

Spatially Multiplexing of Metasurface for Manipulating the Focused Trefoil and Cinquefoil Vector Light Field.

Nanomaterials (Basel) 2021 Mar 27;11(4). Epub 2021 Mar 27.

College of Physics and Electronics, Shandong Normal University, Jinan 250014, China.

The trefoil and cinquefoil vector field are of essential significance for fundamental topology properties as the Hopf link and trefoil knots in the light field. The spatially multiplexing metasurfaces were designed with two sets of periodical nanoslits arranged alternately, each had independent geometric spiral phases and metalens phases to produce and focus vortex of the corresponding circular polarized (CP) light. By arranging the orientations of the two slit sets, the two CP vortices of the desired topological charges were obtained, the superposition of the vortices were realized to generate the vector field. With the topological charges of the vortices set to one and two, and three and two, respectively, the focused trefoil and cinquefoil vector light fields were acquired. The work would be important in broadening the applications of metasurface in areas as vector beam generations and topology of light field.
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http://dx.doi.org/10.3390/nano11040858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066709PMC
March 2021

Heme Oxygenase-1 in Macrophages Impairs the Perfusion Recovery After Hindlimb Ischemia by Suppressing Autolysosome-Dependent Degradation of NLRP3.

Arterioscler Thromb Vasc Biol 2021 05 25;41(5):1710-1723. Epub 2021 Mar 25.

Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

[Figure: see text].
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http://dx.doi.org/10.1161/ATVBAHA.121.315805DOI Listing
May 2021

Regional brain network and behavioral alterations in EGR3 gene transfected rat model of schizophrenia.

Brain Imaging Behav 2021 Mar 15. Epub 2021 Mar 15.

School of Life Science, Beijing Institute of Technology, No.5 Zhongguancun South Street, Haidian District, Beijing, 100081, China.

Schizophrenia is a severe psychiatric disease while its etiology and effective treatment are not completely clear. A rat model of schizophrenia was previously established by transfecting EGR3 gene into the hippocampus of rats. This study aimed to investigate the behavioral and cerebral alterations of the schizophrenic model rats and the risperidone effects. Twenty-six rats were divided into 3 groups: schizophrenia model group (E group), risperidone treatment group (T group), and healthy control group (H group). Morris water maze and open field test were used as behavioral tests, resting-state functional magnetic resonance imaging (fMRI) was performed after EGR3 gene transfection and risperidone therapy. Graph analyses were used for examining cerebral alterations of the rats. Behavioral tests demonstrated reduced spatial working memory and exploring unfamiliar space ability in schizophrenic model rats. Graph analyses revealed reduced regional architectures in the olfactory bulb, nucleus accumbens, and pineal gland in group E compared to group H (p < 0.05), while group T showed increased regional architecture in pineal gland compared to group E (p < 0.05). Besides, the regional architectures in the olfactory bulb, nucleus accumbens were lower in group T than group H, while the hippocampus showed increased regional architecture in group T compared to group H (p < 0.05). Schizophrenia induced several regional alterations in the cerebrum while risperidone can reverse part of these alterations. This study lends support for future research on the pathology of schizophrenia and provides new insights on the role of risperidone in schizophrenia.
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http://dx.doi.org/10.1007/s11682-021-00462-3DOI Listing
March 2021

Measuring Subthalamic Nucleus Volume of Parkinson's Patients and Evaluating Its Relationship with Clinical Scales at Pre- and Postdeep Brain Stimulation Treatment: A Magnetic Resonance Imaging Study.

Biomed Res Int 2021 25;2021:6646416. Epub 2021 Feb 25.

Department of Radiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu Province, China.

This study investigated potential imaging biomarkers for predicting the efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN) in patients with Parkinson's disease (PD). A total of 59 PD patients and 50 healthy control subjects underwent high-resolution 3-dimensional T1-weighted brain magnetic resonance imaging. Bilateral STN volumes were compared between the 2 groups, and a correlation analysis was performed to assess the relationship between bilateral STN volumes or intracranial volume (ICV) and pre- or postoperative clinical scale scores. The results showed that the left STN volume differed significantly between PD patients and controls. In patients, the left STN volume was negatively correlated with pre- and postoperative quality of life scores and positively correlated with Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment scores; ICV was also positively correlated with the MMSE score. These findings indicate that changes in the left STN volume are a useful biomarker for evaluating the clinical outcome of PD patients following DBS.
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http://dx.doi.org/10.1155/2021/6646416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932794PMC
May 2021

Fluoxetine and Ketamine Reverse the Depressive but Not Anxiety Behavior Induced by Lesion of Cholinergic Neurons in the Horizontal Limb of the Diagonal Band of Broca in Male Rat.

Front Behav Neurosci 2021 18;15:602708. Epub 2021 Feb 18.

Zhejiang Provincial Key Laboratory of Addiction, Ningbo Kangning Hospital, School of Medicine, Ningbo University, Ningbo, China.

The basal forebrain cholinergic system is involved in cognitive processes, but the role of the basal forebrain cholinergic system in depression is unknown. We investigated whether a lesion of cholinergic neurons in the horizontal limb of the diagonal band of Broca (HDB) produces depressive-like behavior and whether fluoxetine or ketamine inhibits such depressive-like behaviors. Here, in rats, we used 192 IgG-saporin to eliminate the cholinergic neurons of the HDB and evaluated depressive-like behaviors using a preference test for sucrose solution and the forced swimming test. Fourteen days after the injection of 192 IgG-saporin into the HDB, the rats exhibited a significantly fewer number of choline acetyltransferase positive cell density in HDB, accompanied with neuronal loss in the entire hippocampus. Meanwhile, these rats significantly reduced preference for sucrose solution, increased immobility time in the forced swimming test, reduced locomotor activity, decreased context dependent memory in fear conditioning and the time spent in the open arms of the plus-maze. A single dose of ketamine (10 mg/kg) increased the sucrose solution consumption, reduced the immobility time in the forced swim test (FST), and increased locomotor activity compared to vehicle-treated rats. Moreover, in rats that were continuously treated with fluoxetine (10 mg/kg/day for 11 days), the sucrose solution consumption increased, the immobility time in the FST decreased, and locomotor activity increased compared to vehicle-treated rats. The present results demonstrate that a lesion of HDB cholinergic neurons results in depressive-like and anxiety-like behaviors and that antidepressants such as fluoxetine or ketamine, can reverse these depressive-like behaviors but not anxiety-like behaviors, and suggest that a lesion of HDB cholinergic neurons and followed hippocampus damage may be involved in the pathogenesis of depression.
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http://dx.doi.org/10.3389/fnbeh.2021.602708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930217PMC
February 2021

Nuclear phylotranscriptomics and phylogenomics support numerous polyploidization events and hypotheses for the evolution of rhizobial nitrogen-fixing symbiosis in Fabaceae.

Mol Plant 2021 May 22;14(5):748-773. Epub 2021 Feb 22.

Department of Biology, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA 16802, USA. Electronic address:

Fabaceae are the third largest angiosperm family, with 765 genera and ∼19 500 species. They are important both economically and ecologically, and global Fabaceae crops are intensively studied in part for their nitrogen-fixing ability. However, resolution of the intrasubfamilial Fabaceae phylogeny and divergence times has remained elusive, precluding a reconstruction of the evolutionary history of symbiotic nitrogen fixation in Fabaceae. Here, we report a highly resolved phylogeny using >1500 nuclear genes from newly sequenced transcriptomes and genomes of 391 species, along with other datasets, for a total of 463 legumes spanning all 6 subfamilies and 333 of 765 genera. The subfamilies are maximally supported as monophyletic. The clade comprising subfamilies Cercidoideae and Detarioideae is sister to the remaining legumes, and Duparquetioideae and Dialioideae are successive sisters to the clade of Papilionoideae and Caesalpinioideae. Molecular clock estimation revealed an early radiation of subfamilies near the K/Pg boundary, marked by mass extinction, and subsequent divergence of most tribe-level clades within ∼15 million years. Phylogenomic analyses of thousands of gene families support 28 proposed putative whole-genome duplication/whole-genome triplication events across Fabaceae, including those at the ancestors of Fabaceae and five of the subfamilies, and further analyses supported the Fabaceae ancestral polyploidy. The evolution of rhizobial nitrogen-fixing nodulation in Fabaceae was probed by ancestral character reconstruction and phylogenetic analyses of related gene families and the results support the hypotheses of one or two switch(es) to rhizobial nodulation followed by multiple losses. Collectively, these results provide a foundation for further morphological and functional evolutionary analyses across Fabaceae.
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http://dx.doi.org/10.1016/j.molp.2021.02.006DOI Listing
May 2021

Influence of verapamil on the pharmacokinetics of rotundic acid in rats and its potential mechanism.

Pharm Biol 2021 Dec;59(1):200-208

State Key Laboratory of Drug Delivery and Pharmacokinetics, Tianjin Institute of Pharmaceutical Research, Tianjin, China.

Context: Rotundic acid (RA), a plant-derived pentacyclic triterpene acid, has been reported to possess extensive pharmacological activities. The poor bioavailability limits its further development and potential clinic application.

Objective: To clarify the potential mechanism for poor oral bioavailability.

Materials And Methods: The single-dose pharmacokinetics of orally administered RA (10 mg/kg) in Sprague-Dawley rats without or with verapamil (25 or 50 mg/kg) were investigated. Additionally, MDCKII-MDR1 and Caco-2 cell monolayers, five recombinant human cytochrome P450 (rhCYP) enzymes (1A2, 2C8, 2C9, 2D6 and 3A4), and rat liver microsomes were also conducted to investigate its potential mechanism.

Results: Verapamil could significantly affect the plasma concentration of RA. Co-administered verapamil at 25 and 50 mg/kg, the AUC increased from 432 ± 64.2 to 539 ± 53.6 and 836 ± 116 ng × h/mL, respectively, and the oral clearance decreased from 23.6 ± 3.50 to 18.7 ± 1.85 and 12.2 ± 1.85 L/h/kg, respectively. The MDCKII-MDR1 cell assay showed that RA might be a P-gp substrate. The rhCYPs experiments indicated that RA was mainly metabolized by CYP3A4. Additionally, verapamil could increase the absorption of RA by inhibiting the activity of P-gp, and slow down the intrinsic clearance of RA from 48.5 ± 3.18 to 12.0 ± 1.06 µL/min/mg protein.

Discussion And Conclusions: These findings indicated that verapamil could significantly affect the pharmacokinetic profiles of RA in rats. It was demonstrated that P-gp and CYP3A were involved in the transport and metabolism of RA, which might contribute to the low oral bioavailability of RA.
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http://dx.doi.org/10.1080/13880209.2021.1871634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894426PMC
December 2021

Fanconi Anemia Ortholog FANCM Regulates Meiotic Crossover Distribution in Plants.

Plant Physiol 2021 Feb 12. Epub 2021 Feb 12.

State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Biodiversity Sciences and Ecological Engineering, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai 200438, China.

Meiotic recombination increases genetic diversity and manipulation of its frequency and distribution holds great promise in crop breeding. In Arabidopsis thaliana, FANCM (a homolog of mammalian Fanconi anemia complementation group M) suppresses recombination and its function seems conserved in other species including the rosids Brassica spp. and pea (Pisum sativum), and the monocot rice (Oryza sativa). To examine the role of FANCM during meiotic recombination in lettuce (Lactuca sativa, an asterid), we characterized the function of lettuce LsFANCM and found that it can functionally substitute for AtFANCM in transgenic Arabidopsis plants. Moreover, three independent CRISPR/Cas9-edited lettuce Lsfancm mutants showed reduced pollen viability and seed setting. Unexpectedly, analyses of chromosome behavior revealed that 77.8% of Lsfancm meiocytes exhibited univalents. The normal formation of double-strand breaks in DNA and the discontinuous assembly of synaptonemal complex in Lsfancm mutants supports the hypothesis that LsFANCM might be dispensable for the initiation of meiotic recombination but required for normal synapsis. Furthermore, the frequency of lettuce HEI10 (Human Enhancer of Invasion 10) foci, a marker for Class-I crossovers (COs), was similar between WT and Lsfancm. Strikingly, the distribution of LsHEI10 foci and chiasmata in Lsfancm meiotic chromosomes was markedly different from the WT. A similar alteration in the distribution of Class-I COs was also observed in the Arabidopsis Atfancm mutant. Taken together, these results demonstrate that FANCM is important for shaping the distribution of meiotic Class-I COs in plants, and reveal an evolutionarily divergent role for FANCM in meiotic bivalent formation between Arabidopsis and lettuce.
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http://dx.doi.org/10.1093/plphys/kiab061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154078PMC
February 2021

Phylotranscriptomic insights into Asteraceae diversity, polyploidy, and morphological innovation.

J Integr Plant Biol 2021 Feb 9. Epub 2021 Feb 9.

Department of Biology, the Huck Institutes of the Life Sciences, the Pennsylvania State University, University Park, Pennslyvania, 16802, USA.

Biodiversity is not evenly distributed among related groups, raising questions about the factors contributing to such disparities. The sunflower family (Asteraceae, >26,000 species) is among the largest and most diverse plant families, but its species diversity is concentrated in a few subfamilies, providing an opportunity to study the factors affecting biodiversity. Phylotranscriptomic analyses here of 244 transcriptomes and genomes produced a phylogeny with strong support for the monophyly of Asteraceae and the monophyly of most subfamilies and tribes. This phylogeny provides a reference for detecting changes in diversification rates and possible factors affecting Asteraceae diversity, which include global climate shifts, whole-genome duplications (WGDs), and morphological evolution. The origin of Asteraceae was estimated at ~83 Mya, with most subfamilies having diverged before the Cretaceous-Paleocene boundary. Phylotranscriptomic analyses supported the existence of 41 WGDs in Asteraceae. Changes to herbaceousness and capitulescence with multiple flower-like capitula, often with distinct florets and scaly pappus/receptacular bracts, are associated with multiple upshifts in diversification rate. WGDs might have contributed to the survival of early Asteraceae by providing new genetic materials to support morphological transitions. The resulting competitive advantage for adapting to different niches would have increased biodiversity in Asteraceae.
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http://dx.doi.org/10.1111/jipb.13078DOI Listing
February 2021

Viral vector platforms within the gene therapy landscape.

Signal Transduct Target Ther 2021 Feb 8;6(1):53. Epub 2021 Feb 8.

Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, MA, USA.

Throughout its 40-year history, the field of gene therapy has been marked by many transitions. It has seen great strides in combating human disease, has given hope to patients and families with limited treatment options, but has also been subject to many setbacks. Treatment of patients with this class of investigational drugs has resulted in severe adverse effects and, even in rare cases, death. At the heart of this dichotomous field are the viral-based vectors, the delivery vehicles that have allowed researchers and clinicians to develop powerful drug platforms, and have radically changed the face of medicine. Within the past 5 years, the gene therapy field has seen a wave of drugs based on viral vectors that have gained regulatory approval that come in a variety of designs and purposes. These modalities range from vector-based cancer therapies, to treating monogenic diseases with life-altering outcomes. At present, the three key vector strategies are based on adenoviruses, adeno-associated viruses, and lentiviruses. They have led the way in preclinical and clinical successes in the past two decades. However, despite these successes, many challenges still limit these approaches from attaining their full potential. To review the viral vector-based gene therapy landscape, we focus on these three highly regarded vector platforms and describe mechanisms of action and their roles in treating human disease.
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http://dx.doi.org/10.1038/s41392-021-00487-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868676PMC
February 2021

Primary parasagittal myoepithelioma in a paediatric patient: review of the literature and illustrative case.

BMJ Case Rep 2021 Jan 27;14(1). Epub 2021 Jan 27.

Division of Neurosurgery, Department of Neurosciences, University of the Philippines Manila-Philippine General Hospital, Manila, Philippines.

Myoepithelial tumours are a rare form of salivary gland neoplasm, and their occurrence in the central nervous system is exceedingly rare. The authors report the case of an 18-year-old Filipino man presenting with headache and weakness, and on imaging showing an extensive parasagittal tumour at the left posterior parietal area with extracalvarial extension. There was no systemic disease. The patient underwent surgery to excise the tumour, with histopathology showing findings consistent with myoepithelioma. There was no further treatment, given the benign histology of the lesion, but there was recurrence after 8 months. Repeat surgery was done for the patient and he is for adjuvant radiotherapy. This appears to be the 10th reported case of a central nervous myoepithelioma, and the first case in the Philippines of a primary parasagittal myoepithelioma in a paediatric patient. Further information is needed to provide diagnostic and therapeutic recommendations.
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http://dx.doi.org/10.1136/bcr-2020-236479DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843331PMC
January 2021