Publications by authors named "Min Wei"

970 Publications

Ultra-bright Raman dots for multiplexed optical imaging.

Nat Commun 2021 02 26;12(1):1305. Epub 2021 Feb 26.

Department of Chemistry, Columbia University, New York, NY, USA.

Imaging the spatial distribution of biomolecules is at the core of modern biology. The development of fluorescence techniques has enabled researchers to investigate subcellular structures with nanometer precision. However, multiplexed imaging, i.e. observing complex biological networks and interactions, is mainly limited by the fundamental 'spectral crowding' of fluorescent materials. Raman spectroscopy-based methods, on the other hand, have a much greater spectral resolution, but often lack the required sensitivity for practical imaging of biomarkers. Addressing the pressing need for new Raman probes, herein we present a series of Raman-active  nanoparticles (Rdots) that exhibit the combined advantages of ultra-brightness and compact sizes (~20 nm). When coupled with the emerging stimulated Raman scattering (SRS) microscopy, these Rdots are brighter than previously reported Raman-active organic probes by two to three orders of magnitude. We further obtain evidence supporting for SRS imaging of Rdots at single particle level. The compact size and ultra-brightness of Rdots allows immunostaining of specific protein targets (including cytoskeleton and low-abundant surface proteins) in mammalian cells and tissue slices with high imaging contrast. These Rdots thus offer a promising tool for a large range of studies on complex biological networks.
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http://dx.doi.org/10.1038/s41467-021-21570-0DOI Listing
February 2021

Interactions of fluoroquinolone antibiotics with sodium hypochlorite in bromide-containing synthetic water: Reaction kinetics and transformation pathways.

J Environ Sci (China) 2021 Apr 2;102:170-184. Epub 2020 Oct 2.

School of Marine Sciences, Guangxi Key Laboratory on the Study of Coral Reefs in the South China Sea, Guangxi University, Nanning 530004, China; Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, China.

Seven popular fluoroquinolone antibiotics (FQs) in synthetic marine aquaculture water were subject to sodium hypochlorite (NaClO) disinfection scenario to investigate their reaction kinetics and transformation during chlorination. Reactivity of each FQ to NaClO was following the order of ofloxacin (OFL) > enrofloxacin (ENR) > lomefloxacin (LOM) > ciprofloxacin (CIP) ~ norfloxacin (NOR) > pipemedic acid (PIP), while flumequine did not exhibit reactivity. The coexisting chlorine ions and sulfate ions in the water slightly facilitated the oxidation of FQs by NaClO, while humic acid was inhibitable to their degradation. The bromide ions promoted degradation of CIP and LOM, but restrained oxidation of OFL and ENR. By analysis of liquid chromatography with tandem mass spectrometry (LC-MS/MS), eight kinds of emerging brominated disinfection byproducts (Br-DBPs) caused by FQ were primarily identified in the chlorinated synthetic marine culture water. Through density functional theory calculation, the highest-occupied molecular orbital (HOMO) and the lowest-unoccupied molecular orbital (LUMO) characteristic as well as the charge distribution of the FQs were obtained to clarify transformation mechanisms. Their formation involved decarboxylation, ring-opening/closure, dealkylation and halogenation. Chlorine substitution occurred on the ortho-position of FQs's N4 and bromine substitution occurred on C8 position. The piperazine ring containing tertiary amine was comparatively stable, while this moiety with a secondary amine structure would break down during chlorination. Additionally, logK and logBAF of transformation products were calculated by EPI-Suite to analyze their bioaccumulation. The values indicated that Br-DBPs are easier to accumulate in the aquatic organism relative to their chloro-analogues and parent compounds.
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http://dx.doi.org/10.1016/j.jes.2020.09.013DOI Listing
April 2021

Chemoradiotherapy and Increased Prescription Dose in Esophageal Squamous Cell Cancer: A Retrospective Study.

Biomed Res Int 2021 8;2021:3834040. Epub 2021 Feb 8.

Department of Radiation Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

To analyze the outcomes and adverse events of patients with esophageal squamous cell carcinoma (ESCC) treated with definitive chemoradiation with modified radiotherapy volume and increased radiation dose. This was a retrospective analysis of patients with ESCC treated with definitive chemoradiotherapy at the Sun Yat-sen University Cancer Center (02/2015 to 02/2017). The dose to the planning gross tumor volume (PGTV) and planning clinical tumor volume (PTV1) was 66-68 Gy (2.0-2.2 Gy/fraction). The dose to the planning regional lymph node drainage area volume (PTV2) was 46 Gy (2.0 Gy/fraction). Treatment response, adverse events, progression-free survival (PFS), overall survival (OS), and locoregional failure-free survival (LRFFS) were analyzed. Twenty-six patients were included. The median follow-up was 31 (range, 4.3-51.3) months. Sixteen (61.5%) patients had a complete response, and four (15.4%) achieved a partial response. The objective response rate was 76.9%, and the disease control rate was 80.8%. The median PFS and OS were not achieved. The 4-year PFS was 63.9%, and the 4-year OS was 71.0%. Grade 1-2 and 3-4 radiation-related esophagitis was observed in 15 (57.7%) and one (4.5%) patients, respectively. Grade 1-2 and 3-4 radiation-related pneumonitis was observed in 12 (46.2%) and one (4.5%) patients, respectively. No patients developed radiation-related heart or skin damage. The modified target volume definition and increased dose of definitive radiotherapy combined with chemotherapy in patients with ESCC had low toxicity and might improve survival, but additional trials are necessary to prove the superiority of this strategy.
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http://dx.doi.org/10.1155/2021/3834040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884139PMC
February 2021

Tetrahedral DNA nanostructures functionalized by multivalent microRNA132 antisense oligonucleotides promote the differentiation of mouse embryonic stem cells into dopaminergic neurons.

Nanomedicine 2021 Feb 19:102375. Epub 2021 Feb 19.

Liaoning Provincial Center for Clinical Research on Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China; Liaoning Provincial Key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases, the First Affiliated Hospital, Dalian Medical University, Dalian, People's Republic of China. Electronic address:

MicroRNA132 (miR132) negatively regulates the differentiation of mouse embryonic stem cells (ESCs) into dopaminergic (DAergic) neurons; in contrast, antisense oligonucleotide against miR132 (miR132-ASO) effectively blocks the activity of endogenous miR132 and thereafter promotes the differentiation of DAergic neurons. However, miR132-ASO is difficult to enter cells without suitable delivery system. Tetrahedral DNA nanostructures (TDNs), as a new type of DNA-based nanocarrier, have great potential in biomedical applications, and even have been reported to promote stem cell differentiation. In this study, we developed functional multivalent DNA nanostructures by appending miR132-ASO motifs to three-dimensional TDNs (miR132-ASO-TDNs). Our data clear revealed that miR132-ASO-TDNs exposure can promote the differentiation of ESCs into DAergic neurons as well as elevate DA release from differentiated DAergic neurons. MiR132-ASO-TDNs could serve as a novel biofunctional nanomaterial to improve the efficiency of DAergic neurons differentiation. Our findings may also provide a new approach for stem cells therapy against neurodegenerative diseases.
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http://dx.doi.org/10.1016/j.nano.2021.102375DOI Listing
February 2021

Virus-Free and Live-Cell Visualizing SARS-CoV-2 Cell Entry for Studies of Neutralizing Antibodies and Compound Inhibitors.

Small Methods 2021 Feb 18;5(2):2001031. Epub 2020 Dec 18.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious Diseases School of Public Health & School of Life Sciences Xiamen University Xiamen Fujian 361102 China.

The ongoing corona virus disease 2019 (COVID-19) pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system, a genetically engineered sensor of fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process is developed. In ACE2-expressing cells, it is found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses.
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http://dx.doi.org/10.1002/smtd.202001031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883248PMC
February 2021

Analysis of Main Components in Jujube and Mulberry Extracts by High-Sensitive HPLC-ESI-Q-TOF-MS/MS.

J Chromatogr Sci 2021 Feb 17. Epub 2021 Feb 17.

Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan 430072, P R China.

In order to comprehensively reflect the cigarette quality, a method combining direct injection of diluted sample with high sensitive high-performance liquid chromatography (HPLC)- electrospray (ESI)- quadrupole (Q)- time of flight (TOF)- tandem mass spectrometry (MS/MS) was developed for the identification of major components of cigarette essences (jujube and mulberry extracts). Based on the observed relative molecular mass, MS/MS fragmentation behavior, MS/MS database and related literatures, the components of the jujube extract and mulberry extract were identified. The result shows that the composition of jujube extract and mulberry extract has some similarity. They all mainly contain amino acids, free amino compounds and Maillard reaction products, which are the main constituents of a cigarette essence.
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http://dx.doi.org/10.1093/chromsci/bmaa133DOI Listing
February 2021

Activated Microglia Exosomes Mediated miR-383-3p Promotes Neuronal Necroptosis Through Inhibiting ATF4 Expression in Intracerebral Hemorrhage.

Neurochem Res 2021 Feb 16. Epub 2021 Feb 16.

Department of Neurosurgery, Clinical Medical College, Yangzhou University, No. 98 of Nantong West Road, Yangzhou, 225001, Jiangsu Province, China.

Intracerebral hemorrhage (ICH) is the second largest type of stroke, with high mortality and morbidity, and most patients have severe sequelae. Brain injury induced by ICH includes primary damage and secondary damage, and the secondary brain injury is the main reason of neurological impairment. The hallmark of secondary brain injury is cell death. Necroptosis is a type of the cell death and plays vital roles in various neurological diseases, but the roles of necroptosis in ICH are still not fully known. Microglia cell is the type of immune cell, plays protective roles in nerve damage and modulates the activity of neurons through secreting exosomes. Exosome-contained miRNAs are also involved in the regulating neuronal activity. However, the roles and the mechanisms of microglia-secreted exosomes miRNAs in ICH neurons necroptosis need to further explore. In this study, ICH model was construct in rats and cells. Injury of cells in brain was detected by PI staining. Necroptosis in rats and cells was detected by western blot and flow cytometry. The expression of miR-383-3p was detected by RT-qPCR. The roles of activated microglia-secreted exosomes and exosome-contained miR-383-3p were detected through co-culturing medium or exosomes with neurons. The target gene of miR-383-3p was determined by luciferase assay and the expression of target gene was detected by western blot. Rescue experiments were used to confirm the mechanism of miR-383-3p in neurons necroptosis. The miR-383-3p role was verified in vivo through injecting miR-383-3p mimic into ICH rats. Here, we found that the necroptosis of neurons was increased in ICH rats through detecting the expression of RIP1 and RIP3 and PI staining. Microglia that activated by ICH promote neurons necroptosis through secreting exosomes and transferring miR-383-3p into neurons. In mechanism, miR-383-3p negatively regulated the expression of ATF4 and then promoted the necroptosis of neurons. Overall, our results provide a novel molecular basis to neurons necroptosis in ICH and may provide a new strategy to retard the secondary brain injury of ICH.
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http://dx.doi.org/10.1007/s11064-021-03268-3DOI Listing
February 2021

Enhanced antitumor efficacy of a novel oncolytic vaccinia virus encoding a fully monoclonal antibody against T-cell immunoglobulin and ITIM domain (TIGIT).

EBioMedicine 2021 Feb 10;64:103240. Epub 2021 Feb 10.

Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, No. 22, Hankou Road, Nanjing 210093, China. Electronic address:

Background: Oncolytic virotherapy with vaccinia virus (VV) can lead to effective anti-tumor immunity by turning "cold" tumors into "hot" tumors. However, its therapeutic potential is affected by the tumor's local immunosuppressive tumor microenvironment (TME). Therefore, it is necessary to explore the use of immune checkpoint inhibitors to arm oncolytic VVs to enhance their anti-tumor efficacy.

Methods: A novel recombinant oncolytic VV, VV-α-TIGIT, which encoded a fully monoclonal antibody against T-cell immunoglobulin and ITIM domain (TIGIT) was generated by homologous recombination with a shuttle plasmid. The anti-tumor efficacy of the VV-α-TIGIT was investigated in several subcutaneous and ascites tumor models.

Findings: The functional α-TIGIT was sufficiently produced and secreted by tumor cells infected with VV-α-TIGIT, which effectively replicated in tumor cells leading to significant oncolysis. Intratumoral injection of VV-α-TIGIT improved anti-tumor efficacy in several murine subcutaneous tumor models compared to VV-Control (without α-TIGIT insertion). Intraperitoneal injection of VV-α-TIGIT achieved approximately 70% of complete tumor regression in an ascites tumor model. At the same time, treatment with VV-α-TIGIT significantly increased the recruitment and activation of T cells in TME. Moreover, the in vivo anti-tumor activity of VV-α-TIGIT was largely dependent on CD8 T cell-mediated immunity. Finally, the tumor-bearing mice cured of VV-α-TIGIT treatment resisted rechallenge with the same tumor cells, suggesting a long-term persistence of tumor-specific immunological memory.

Interpretation: The recombinant oncolytic virus VV-α-TIGIT successfully combines the advantages of oncolytic virotherapy and intratumorally expression of immune checkpoint inhibitor against TIGIT. This novel strategy can provide information on the optimal design of novel antibody-armed oncolytic viruses for cancer immunotherapy.

Funding: This work was supported by the National Natural Science Foundation of China (81773255, 81472820, and 81700037), the Science and Technology Innovation Foundation of Nanjing University (14913414), and the Natural Science Foundation of Jiangsu Province of China (BK20171098).
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http://dx.doi.org/10.1016/j.ebiom.2021.103240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878184PMC
February 2021

Recombinant oncolytic adenovirus expressing a soluble PVR elicits long-term antitumor immune surveillance.

Mol Ther Oncolytics 2021 Mar 17;20:12-22. Epub 2020 Nov 17.

Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, China.

Oncolytic virotherapy (OVT) has been suggested to be effective. However, the suppressive effects of checkpoints and insufficient costimulatory signals limit OVT-induced antitumor immune responses. In this study, we constructed a replicative adenovirus, Ad5sPVR, that expresses the soluble extracellular domain of poliovirus receptor (sPVR). We showed that sPVR can bind to both T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) and CD226, and the binding affinity of sPVR to TIGIT is stronger than that of PVR to CD226. In the H22 hepatocellular carcinoma (HCC) ascites model, Ad5sPVR treatment increased the infiltration of CD8 T cells and the release of interferon (IFN)-γ, exhibiting an antitumor effect with long-term tumor-specific immune surveillance. In line with this, Ad5sPVR also effectively improved antitumor outcomes in solid tumors. In conclusion, while Ad5sPVR plays a role in oncolysis and transforms cold tumors into hot tumors, sPVR expressed by Ad5sPVR can block the PVR/TIGIT checkpoint and activate CD226, thereby greatly improving the efficacy of OVT. This study provides a new way to develop potential oncolytic viral drugs.
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http://dx.doi.org/10.1016/j.omto.2020.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851489PMC
March 2021

Recent advances in innovative strategies for enhanced cancer photodynamic therapy.

Theranostics 2021 15;11(7):3278-3300. Epub 2021 Jan 15.

State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China.

Photodynamic therapy (PDT), a non-invasive therapeutic modality, has received increasing attention owing to its high selectivity and limited side effects. Although significant clinical research progress has been made in PDT, the breadth and depth of its clinical application have not been fully realized due to the limitations such as inadequate light penetration depth, non-targeting photosensitizers (PSs), and tumor hypoxia. Consequently, numerous investigations put their emphasis on innovative strategies to overcome the aforementioned limitations and enhance the therapeutic effect of PDT. Herein, up-to-date advances in these innovative methods for PDT are summarized by introducing the design of PS systems, their working mechanisms and application examples. In addition, current challenges of these innovative strategies for clinical application, and future perspectives on further improvement of PDT are also discussed.
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http://dx.doi.org/10.7150/thno.54227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847668PMC
January 2021

A Novel p.Pro871Leu Missense Mutation in SPECC1L Gene Causing Craniosynostosis in a patient.

Orthod Craniofac Res 2021 Feb 1. Epub 2021 Feb 1.

Department of Plastic and Reconstructive Surgery, Shanghai 9thPeople's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.

Introduction: Craniosynostosis is one of the most common craniofacial abnormalities. It involves premature closure of one or more cranial sutures. Mutations in many genes have been and continue to be identified in patients. Settings and sample population: Whole blood samples were collected from the patient and family members.

Material And Methods: Whole exome sequencing was performed to identify potential mutations in the patient. The results were verified by Sanger sequencing by comparing SPECC1L gene sequence of blood samples from 100 unrelated population-matched controls.

Results: The patient presented with craniosynostosis with fusion of the bicoronal and sagittal sutures. A novel missense mutation (c.2612C>T, p.Pro871Leu) in the SPECC1L gene was identified. Gene analysis showed a missense mutation in exon1 of SPECC1L that led to an amino acid substitution in the region between CCD3 and calponin homology domain.

Conclusion: Our observations expand the molecular spectrum of gene mutations in craniosynostosis and emphasize the importance of gene testing in the diagnosis of craniosynostosis. The observations also reinforce the characteristics of SPECC1L-related cranial disorders.
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http://dx.doi.org/10.1111/ocr.12473DOI Listing
February 2021

The Complex Roles and Therapeutic Implications of mA Modifications in Breast Cancer.

Front Cell Dev Biol 2020 11;8:615071. Epub 2021 Jan 11.

Department of Breast and Thyroid Surgery, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Accumulating evidence indicates that N-methyladenosine (mA), which directly regulates mRNA, is closely related to multiple biological processes and the progression of different malignancies, including breast cancer (BC). Studies of the aberrant expression of mA mediators in BC revealed that they were associated with different BC subtypes and functions, such as proliferation, apoptosis, stemness, the cell cycle, migration, and metastasis, through several factors and signaling pathways, such as Bcl-2 and the PI3K/Akt pathway, among others. Several regulators that target mA have been shown to have anticancer effects. Fat mass and obesity-associated protein (FTO) was identified as the first mA demethylase, and a series of inhibitors that target FTO were reported to have potential for the treatment of BC by inhibiting cell proliferation and promoting apoptosis. However, the exact mechanism by which mA modifications are regulated by FTO inhibitors remains unknown. mA modifications in BC have only been preliminarily studied, and their mechanisms require further investigation.
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http://dx.doi.org/10.3389/fcell.2020.615071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829551PMC
January 2021

Effects of acute ammonia exposure on antioxidant and detoxification metabolism in clam Cyclina sinensis.

Ecotoxicol Environ Saf 2021 Mar 19;211:111895. Epub 2021 Jan 19.

Jiangsu Key Laboratory of Marine Bioresources and Environment, Jiangsu Ocean University, Lianyungang, Jiangsu Province 222005, China.

To investigate the defensive strategies of clam Cyclina sinensis in response to environmental ammonia exposure, we investigate the 96 h median lethal concentration (LC-96 h) and the 96 h safe concentration (SC) of total ammonia nitrogen (TAN) for C. sinensis, and on the basis we examined glutamine synthetase (GS) activity, glutamine content, urea content and the antioxidant enzyme activities of super oxide dismutase (SOD) and catalase (CAT) in 96 h at three different levels of TAN as 0 (control), 73.94 (T1) and 227.04 mg/L (T2). Results showed that LC-96 h and SC for C. sinensis were 65.79 and 6.58 mg/L, respectively. The LC-96 h and SC of NH were 1.70 and 0.17 mg/L, respectively. Ammonia exposure had significantly effects on SOD and CAT activities in the hepatopancreas tissue. Both the level of SOD activity and CAT activity increased with increasing concentration of TAN. No significant differences between T1 and T2 were found in GS activity from 3 h to 96 h after exposed to ammonia, whereas they were significantly higher than those in the control. Both the level of glutamine content in T1 and T2 increased significantly from 6 h to 24 h after exposed to ammonia and they were significantly higher than those in the control. There were no significantly differences were found in the level of urea concentration between T1 and T2 from 6 h to 96 h, while they were significantly higher those in the control. In conclusion, enhancing hepatopancreas antioxidant responses as well as converting ammonia into glutamine and urea worked in combination to allow C. sinensi to defend against acute ammonia exposure.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111895DOI Listing
March 2021

BMP-2 and VEGF-A modRNAs in collagen scaffold synergistically drive bone repair through osteogenic and angiogenic pathways.

Commun Biol 2021 Jan 19;4(1):82. Epub 2021 Jan 19.

Institute of Pediatric Translational Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University, 1678 Dong Fang Road, 200127, Shanghai, China.

Bone has a remarkable potential for self-healing and repair, yet several injury types are non-healing even after surgical or non-surgical treatment. Regenerative therapies that induce bone repair or improve the rate of recovery are being intensely investigated. Here, we probed the potential of bone marrow stem cells (BMSCs) engineered with chemically modified mRNAs (modRNA) encoding the hBMP-2 and VEGF-A gene to therapeutically heal bone. Induction of osteogenesis from modRNA-treated BMSCs was confirmed by expression profiles of osteogenic related markers and the presence of mineralization deposits. To test for therapeutic efficacy, a collagen scaffold inoculated with modRNA-treated BMSCs was explored in an in vivo skull defect model. We show that hBMP-2 and VEGF-A modRNAs synergistically drive osteogenic and angiogenic programs resulting in superior healing properties. This study exploits chemically modified mRNAs, together with biomaterials, as a potential approach for the clinical treatment of bone injury and defects.
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http://dx.doi.org/10.1038/s42003-020-01606-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815925PMC
January 2021

Functional nanoassemblies for the diagnosis and therapy of Alzheimer's diseases.

Wiley Interdiscip Rev Nanomed Nanobiotechnol 2021 Jan 18:e1696. Epub 2021 Jan 18.

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects populations around the world. Many therapeutics have been investigated for AD diagnosis and/or therapy, but the efficacy is largely limited by the poor bioavailability of drugs and by the presence of the blood-brain barrier. Recently, the development of nanomedicines enables efficient drug delivery to the brain, but the complex pathological mechanism of AD prevents them from successful treatment. As a type of advanced nanomedicine, multifunctional nanoassemblies self-assembled from nanoscale imaging or therapeutic agents can simultaneously target multiple pathological factors, showing great potential in the diagnosis and therapy of AD. To help readers better understand this emerging field, in this review, we first introduce the pathological mechanisms and the potential drug candidates of AD, as well as the design strategies of nanoassemblies for improving AD targeting efficiency. Moreover, the progress of dynamic nanoassemblies that can diagnose and/or treat AD in response to the endogenous or exogenous stimuli will be described. Finally, we conclude with our perspectives on the future development in this field. The objective of this review is to outline the latest progress of using nanoassemblies to overcome the complex pathological environment of AD for improved diagnosis and therapy, in hopes of accelerating the future development of intelligent AD nanomedicines. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Diagnostic Tools > in vivo Nanodiagnostics and Imaging.
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http://dx.doi.org/10.1002/wnan.1696DOI Listing
January 2021

[Mid-term effectiveness of anterior cruciate ligament revision].

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2021 Jan;35(1):58-63

Department of Orthopaedics, the First Medical Center of Chinese PLA General Hospital, Beijing, 100853, P.R.China.

Objective: To assess the mid-term effectiveness of anterior cruciate ligament (ACL) revision and to analyze the relevant factors that may affect the surgical outcomes.

Methods: The clinical data of 24 patients who underwent ACL revision surgery between April 2009 and July 2018 and were followed up for more than 2 years were retrospectively analyzed. There were 20 males and 4 females with a median age of 30 years [interquartile distance (IQR) was (25, 36) years]. The median body mass index was 24.45 kg/m and IQR was (22.93, 25.93) kg/m . The median time between ACL revision and reconstruction was 41 months and IQR was (15, 85) months. The direct cause of the failure of reconstruction surgery included 14 cases of trauma, 8 cases of no obvious cause, and 2 cases of infection. During the revision operation, 14 patients had a poor bone tunnel position, all of which were drilled with new tunnels, the remaining 10 patients were freshly modified on the basis of the original bone tunnel. Seventeen patients used autogenous tendon revision, 7 patients used LARS ligament; 16 patients had cartilage injury. The Lysholm score, the International Knee Documentation Committee (IKDC) score, and the Tegner sports rating score were used for functional evaluation before operation, at 1 year after operation, and at last follow-up. The Likert satisfaction score was recorded at last follow-up.

Results: Patients were followed up with a median time of 47 months and IQR was (32, 61) months. The Lysholm score, IKDC score, and Tegner sports rating score were significantly improved at 1 year after operation and at last follow-up when compared with preoperative scores ( <0.05). There was no significant difference between at last follow-up and at 1 year after operation ( >0.05). At last follow-up, the median Likert satisfaction score was 4.0 and IQR was (3.0, 4.5). According to the presence or absence of cartilage damage and the type of graft, the above scores at last follow-up were compared between the groups, and the differences were not significant ( >0.05). At last follow-up, 2 patients had graft fractures due to trauma again, and autogenous iliac bones were taken to fill the bone tunnel, and the second stage was revised; the rest of the patients recovered satisfactorily.

Conclusion: With preoperative identification of the cause of ACL reconstruction failure, the stability and function of knee joint can be significantly improved by selecting appropriate bone tunnels and grafts during the revision and by active rehabilitation exercises.
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http://dx.doi.org/10.7507/1002-1892.202008125DOI Listing
January 2021

Greater Biofilm Formation and Increased Biodegradation of Polyethylene Film by a Microbial Consortium of sp. and sp.

Microorganisms 2020 Dec 12;8(12). Epub 2020 Dec 12.

State Key Laboratory of Grassland Agro-Ecosystems, Institute of Arid Agroecology, School of Life Sciences, Lanzhou University, Lanzhou 730000, China.

The widespread use of polyethylene (PE) mulch films has led to a significant accumulation of plastic waste in agricultural soils. The biodegradation of plastic waste by microorganisms promises to provide a cost-effective and environmentally-friendly alternative for mitigating soil plastic pollution. A large number of microorganisms capable of degrading PE have been reported, but degradation may be further enhanced by the cooperative activity of multiple microbial species. Here, two novel strains of sp. and sp. were isolated from agricultural soils and shown to grow with PE film as a sole carbon source. sp. mainly grew in the suspension phase of the culture, and sp. formed substantial biofilms on the surface of the PE film, indicating that these strains were of different metabolic types and occupied different microenvironments with contrasting nutritional access. Individual strains were able to degrade the PE film to some extent in a 90-day inoculation experiment, as indicated by decreased hydrophobicity, increased carbonyl index and CO evolution, and the formation of biofilms on the film surface. However, a consortium of both strains had a much greater effect on these degradation properties. Together, these results provide new insights into the mechanisms of PE biodegradation by a microbial consortium composed of different types of microbes with possible metabolic complementarities.
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http://dx.doi.org/10.3390/microorganisms8121979DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764375PMC
December 2020

NiSn Atomic Pair on Integrated Electrode for Synergistic Electrocatalytic CO2 Reduction.

Angew Chem Int Ed Engl 2020 Dec 14. Epub 2020 Dec 14.

Beijing University of Chemical Technology, Science College, Beisanhuan East Road No.15, 100029, Beijing, CHINA.

Electrochemical CO 2 reduction (CO 2 RR) to value-added chemicals offers an efficient way to mitigate global warming and energy supply issues. However, the development of highly efficient electrocatalysts for CO 2 RR to boost reaction efficiency and guide understanding of catalytic mechanism remains a huge challenge. Herein, we demonstrate a NiSn atomic pair electrocatalyst (NiSn-APC) on a hierarchical integrated electrode, which exhibits a synergistic effect in simultaneously promoting the activity and selectivity of CO 2 RR to formate. The NiSn atomic pair consist of adjacent Ni and Sn coordinated with four nitrogen atoms (N 4 -Ni-Sn-N 4 ) respectively, which is confirmed by high-angle annular dark field-scanning transmission electron microscopy (HAADF-STEM) and extended X-ray absorption fine structure (EXAFS). Typically, the as-prepared NiSn-APC displays an exceptional activity toward CO 2 RR to formate with a turnover frequency of 4752 h -1 , a formate productivity of 36.7 mol h -1 g Sn -1 and an utilization degree of active sites (57.9%), which are superior to the previously reported single-atomic catalysts (SACs). Moreover, both in situ attenuated total reflection-infrared (ATR-IR) spectroscopy and density functional theory (DFT) calculation verify the electron redistribution of Sn imposed by adjacent Ni, which reduces the energy barrier of *OCHO intermediate and makes this potential-determining step thermodynamically spontaneous. The NiSn synergistic catalysis for CO 2 RR in this work provides a successful paradigm for rational design and preparation of atomic pair electrocatalysts with largely enhanced performance.
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http://dx.doi.org/10.1002/anie.202014655DOI Listing
December 2020

Sequential release of double drug (graded distribution) loaded gelatin microspheres/PMMA bone cement.

J Mater Chem B 2021 01;9(2):508-522

Institute of Orthopaedics, Xi'jing Hospital, Fourth Military Medical University, Xi'an 710032, P. R. China.

Drugs are loaded into PMMA bone cement to reduce the risk of infection in freshly implanted prostheses or to promote the differentiation and growth of osteoblasts. However, the same method of loading of drugs in the bone cement cannot simultaneously achieve an effective antibacterial response and long-term treatment outcomes for osteoporosis based on a patient's clinical needs. In the present study, gentamicin sulfate (GS)/alendronate (ALN)-dual-loaded gelatin modified PMMA bone cement (GAPBC) was fabricated to provide rapid and continuous antibiotic release and long-term anti-osteoporotic therapy. Specifically, the gelatin microspheres were loaded with the drugs using separate methodologies, namely, ALN was loaded during fabrication of the gelatin microspheres after which GS was absorbed onto the gelatin from solution. The results demonstrate that sequential release of the GS and ALN was achieved, GS release playing a major role over the first 24 hours and ALN release dominant after 3 weeks of immersion in PBS, resulting from the graded distribution within the gelatin microspheres, and the final drug release ratio of GS (73.6%) and ALN (68.5%) from the modified bone cement was significantly higher than from PMMA bone cement. Therefore, GAPBC represents a potential drug carrier for future clinical applications.
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http://dx.doi.org/10.1039/d0tb01452dDOI Listing
January 2021

Multicomponent Transition Metal Dichalcogenide Nanosheets for Imaging-Guided Photothermal and Chemodynamic Therapy.

Adv Sci (Weinh) 2020 Dec 30;7(23):2000272. Epub 2020 Sep 30.

State Key Laboratory of Chemical Resource Engineering Beijing Advanced Innovation Center for Soft Matter Science and Engineering Beijing University of Chemical Technology Beijing 100029 P. R. China.

Transition metal dichalcogenides (TMDs) have received considerable attention due to their strong absorption in the near-infrared (NIR) region, strong spin-orbit coupling, and excellent photothermal conversion efficiency (PCE). Herein, CoFeMn dichalcogenide nanosheets (CFMS NSs) are prepared via facile vulcanization of a lamellar CoFeMn-layered double hydroxide (LDH) precursor followed by polyvinyl pyrrolidone modification (to give CFMS-PVP NSs), and found to show excellent photoacoustic (PA) imaging and synergistic photothermal/chemodynamic therapy (PTT/CDT) performance. The as-prepared CFMS-PVP NSs inherit the ultrathin morphology of the CoFeMn-LDH precursor and exhibit an outstanding photothermal performance with a of 89.0%, the highest PCE reported to date for 2D TMD materials. Moreover, 50% of maximum catalytic activity (Michaelis-Menten constant, ) is attained by CFMS-PVP NSs with 0.26 × 10 m HO at 318 K, markedly lower than the endogenous concentration of HO inside tumor cells. In addition, complete apoptosis of HepG2 cancer cells and complete tumor elimination in vivo are observed after treatment with CFMS-PVP NSs at a low dose, substantiating the NSs' remarkable PTT/CDT efficacy. This work provides a new and facile approach for the synthesis of high-quality multicomponent TMD nanosheets with precise process control, the potential for mass production, and outstanding performance, providing great promise in cancer theranostics.
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http://dx.doi.org/10.1002/advs.202000272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709983PMC
December 2020

Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infection.

Emerg Microbes Infect 2021 Dec;10(1):37-50

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People's Republic of China.

Hepatitis B e antigen (HBeAg) is a widely used marker both for chronic hepatitis B (CHB) clinical management and HBV-related basic research. However, due to its high amino acid sequence homology to hepatitis B core antigen (HBcAg), most of available anti-HBe antibodies are cross-reactive with HBcAg resulting in high interference against accurate measurement of the status and level of HBeAg. In the study, we generated several monoclonal antibodies (mAbs) targeting various epitopes on HBeAg and HBcAg. Among these mAbs, a novel mAb 16D9, which recognizes the SKLCLG (aa -10 to -5) motif on the N-terminal residues of HBeAg that is absent on HBcAg, exhibited excellent detection sensitivity and specificity in pairing with another 14A7 mAb targeting the HBeAg C-terminus (STLPETTVVRRRGR, aa141 to 154). Based on these two mAbs, we developed a novel chemiluminescent HBeAg immunoassay (NTR-HBeAg) which could detect HBeAg derived from various HBV genotypes. In contrast to widely used commercial assays, the NTR-HBeAg completely eliminated the cross-reactivity with secreted HBcAg from precore mutant (G1896A) virus in either cell culture or patient sera. The improved specificity of the NTR-HBeAg assay enables its applicability in cccDNA-targeting drug screening in cell culture systems and also provides an accurate tool for clinical HBeAg detection.
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http://dx.doi.org/10.1080/22221751.2020.1862631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832009PMC
December 2021

Combining the best of two worlds: Stimulated Raman excited fluorescence.

J Chem Phys 2020 Dec;153(21):210901

Department of Chemistry, Columbia University, New York, New York 10027, USA.

The pursuit of a hybrid spectroscopy that combines the superb sensitivity of fluorescence and the high chemical specificity of Raman scattering has lasted for 40 years, with multiple experimental and theoretical attempts in the literature. It was only recently that the stimulated Raman excited fluorescence (SREF) process was successfully observed in a broad range of fluorophores. SREF allows single-molecule vibrational spectroscopy and imaging in the optical far field without relying on plasmonic enhancement. In this perspective, we will first review the historical efforts that lead to the successful excitation and detection of SREF, followed by the underlying physical principles, then the remaining technical challenges will be discussed, and, at last, the future opportunities in this old but yet newly emerged spectroscopy are outlined.
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http://dx.doi.org/10.1063/5.0030204DOI Listing
December 2020

Discovery of Pamiparib (BGB-290), a Potent and Selective Poly (ADP-ribose) Polymerase (PARP) Inhibitor in Clinical Development.

J Med Chem 2020 12 2;63(24):15541-15563. Epub 2020 Dec 2.

Poly (ADP-ribose) polymerase (PARP) plays a significant role in DNA repair responses; therefore, this enzyme is targeted by PARP inhibitors in cancer therapy. Here we have developed a number of fused tetra- or pentacyclic dihydrodiazepinoindolone derivatives with excellent PARP enzymatic and cellular PARylation inhibition activities. These efforts led to the identification of pamiparib (BGB-290, ), which displays excellent PARP-1 and PARP-2 inhibition with IC of 1.3 and 0.9 nM, respectively. In a cellular PARylation assay, this compound inhibits PARP activity with IC = 0.2 nM. Cocrystal of pamiparib shows similar binding sites with PARP with other PARP inhibitors, but pamiparib is not a P-gp substrate and shows excellent drug metabolism and pharmacokinetics (DMPK) properties with significant brain penetration (17-19%, mice). The compound is currently being investigated in phase III clinical trials as a maintenance therapy in platinum-sensitive ovarian cancer and gastric cancer.
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http://dx.doi.org/10.1021/acs.jmedchem.0c01346DOI Listing
December 2020

Comprehensive Analysis of Volatile Compounds in Mouthpiece Cigarette Adhesive by Coupling Headspace with Gas Chromatography-Mass Spectrometry.

J AOAC Int 2020 Nov 30. Epub 2020 Nov 30.

Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, China.

Background: Some volatile compounds in mouthpiece cigarette adhesive emit irritating odors and affect the taste of smoking cigarettes. Therefore, it is necessary to monitor the volatile compounds in mouthpiece cigarette adhesive.

Objectives: A rapid and simple analytical method of volatile compounds in mouthpiece cigarette adhesive was established.

Methods: In this study, headspace (HS) injection coupled with gas chromatography-mass spectrometry (GC-MS) was utilized for qualitative and quantitative analysis. Initially, the volatile compounds in mouthpiece cigarette adhesives were detected by HS-GC-MS, followed by spectrum library retrieval. The detected compounds with the similarity to spectrum library of more than 85% were further identified by comparing the retention time and mass spectra of the detected volatile compounds and those of the corresponding standard samples. The quantitative analysis of 9 identified volatile compounds was performed.

Results: Eleven volatile compounds in the mouthpiece cigarette adhesive were accurately identified. The quantitative analytical method of 9 volatile compounds in mouthpiece cigarette adhesive was validated to have good linearities (R2 > 0.9932) within the range of 20-5000 ng/g. The detection limits of 9 compounds were within the range of 3.1-147.7 ng/g. The intra- and inter-day relative standard deviations (RSDs) were less than 19.8%. The recoveries of these 9 compounds spiked into mouthpiece cigarette adhesive were from 68.1% to 108.3%.

Conclusions: The proposed method is rapid, simple, and accurate for qualitative and quantitative analysis of volatile compounds in the mouthpiece cigarette adhesive.

Highlights: The developed analytical method is expected to be used to monitor volatile compounds in various adhesives.
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http://dx.doi.org/10.1093/jaoacint/qsaa160DOI Listing
November 2020

Applications of ion level nanosensors for neuroscience research.

Nanomedicine (Lond) 2020 12 30;15(29):2871-2881. Epub 2020 Nov 30.

Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.

Ion activities are tightly associated with brain physiology, such as intracranial cell membrane potential, neural activity and neuropathology. Thus, monitoring the ion levels in the brain is of great significance in neuroscience research. Recently, nanosensors have emerged as powerful tools for monitoring brain ion levels and dynamics. With controllable structures and functions, nanosensors have been intensively used for monitoring neural activity and cell function and can be used in disease diagnosis. Here, we summarize the recent advances in the design and application of ion level nanosensors at different physiological levels, aiming to draw a connection of the interrelated intracranial ion activities. Furthermore, perspectives on the rationally designed ion level nanosensors in understanding the brain functions are highlighted.
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http://dx.doi.org/10.2217/nnm-2020-0320DOI Listing
December 2020

Ultrathin-shell IrCo hollow nanospheres as highly efficient electrocatalysts towards the oxygen evolution reaction in acidic media.

Nanoscale 2020 Dec 26;12(47):24070-24078. Epub 2020 Nov 26.

Guangxi Key Laboratory of Electrochemical Energy Materials; Key Laboratory of New Processing Technology for Non-ferrous Metal and Materials, Ministry of Education; Collaborative Innovation Center of Sustainable Energy Materials, School of Physical Science and Technology, Guangxi University, Nanning, 530004, China.

Improving the utilization of Ir electrocatalysts for the oxygen evolution reaction (OER) to significantly reduce their loading is essential for low-cost hydrogen production in proton exchange membrane water electrolysis. Herein, IrCo hollow nanospheres featuring a novel structure with ultrathin continuous shells which have only eleven atomic layers (2.26 nm) were synthesized by a facile sequential reduction route using NaBH as a reducing agent at room temperature. It is revealed that the key intermediate in the formation of hollow nanospheres is amorphous cobalt boride formed between Co and NaHB in the first reducing step. The average diameter of the IrCo nanospheres was found to be 73.71 nm with the atomic ratio of 47.1% and 52.9% for Co and Ir, respectively. The IrCo hollow nanospheres exhibit highly efficient OER activity and long-term durability with a low overpotential of 284 mV at 10 mA cm (32.5 μg cm) and a high mass activity of 8.49 A mg (5.7 times higher than that of commercial IrO (1.49 A mg) at 1.7 V. The performance is also proved using an overall water splitting device with the overpotential of 318 mV to achieve 10 mA cm as well as a 17 mV shift at 5 mA cm after 14 h. This improvement is critically attributed to the advantages of the hollow structure, ultrathin continuous shells which are oxidized into IrOin situ and strong lattice strain effects induced by the specific hollow structure and alloying Co into Ir crystal lattices (1.6% against metallic iridium). These characteristics endow the hollow nanospheres with great potential to minimize the Ir loading dramatically for practical applications, compared to other previously reported structures like nanoparticles, nanoneedles and nanowires.
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http://dx.doi.org/10.1039/d0nr06601jDOI Listing
December 2020

Enhanced Enzymatic Hydrolysis and Structure Properties of Bamboo by Moderate Two-Step Pretreatment.

Appl Biochem Biotechnol 2020 Nov 25. Epub 2020 Nov 25.

Institute of Chemical Industry of Forest Products, CAF, National Engineering Laboratory for Biomass Chemical Utilization; Key and Open Laboratory of Forest Chemical Engineering, SFA; Key Laboratory of Biomass Energy and Material, Nanjing, 210042, Jiangsu Province, People's Republic of China.

A moderate two-step pretreatment method was investigated to improve the enzymatic saccharification of bamboo residues. SEM and FTIR were employed to characterize the structure changes. Fed-batch enzymatic saccharification was performed to obtain high concentration of fermentable sugar. Bamboo was impregnated at low severity of conditions (room temperature, 2% HSO or 2% NaOH, 48 h) to initially alter the structure of bamboo, and then further pretreated by steam explosion at 1.0 MPa for 6 min. The highest delignification of 51% and the highest enzymatic hydrolysis of 47.1% were reached at 2% NaOH impregnation followed by steam explosion. The changes in the structural characteristics showed beneficial effects on the enzymatic hydrolysis. When a mixer of cellulase (30 FPU) and β-glucosidase (10 CBU) was further used, the maximum enzymatic hydrolysis of 78.9% and total glucose yield of 68.2% were obtained. The maximum sugar release from the holocellulose was 500 mg/g bamboo, approximately 83.3% conversion efficiency based on monomeric sugar recovery. With fed-batch saccharification, a final substrate loading of 30% brought 107.7 g/L glucose, 35.81 g/L xylose, and 7.82 g/L arabinose release, respectively. This study provided an effective strategy for potential utilization of bamboo residues.
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http://dx.doi.org/10.1007/s12010-020-03472-xDOI Listing
November 2020

Different functional connectivity modes of the right fronto-insular cortex in akinetic-rigid and tremor-dominant Parkinson's disease.

Neurol Sci 2020 Nov 24. Epub 2020 Nov 24.

Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China.

Background: Patients with akinetic-rigid Parkinson's disease (AR-PD) are more prone to cognitive decline and depressive symptoms than tremor-dominant PD (TD-PD) patients. The right fronto-insular cortex (rFIC), as a key node of salience network, plays a critical role in the switching between central executive network and default mode network. In this study, we explored the functional connectivity mode of rFIC with triple-brain networks, namely default mode network, salience network, and central executive network, in two motor subtypes of PD.

Methods: We recruited 44 PD patients (including the TD-PD group and AR-PD group) and 18 age-matched healthy controls (HCs). We performed functional connectivity (FC) analysis of resting-state functional MRI.

Results: Compared with TD-PD, decreased FC were found in the right insular cortex and bilateral anterior cingulate gyrus in AR-PD. Compared with HCs, decreased FC in the bilateral insula, the anterior cingulate gyrus, the precentral gyrus, and the right medial frontal gyrus were found; therein, the FC value of rFIC-precentral gyrus was positively correlated with the Unified Parkinson's Disease Rating Scale-II score in AR-PD (p = 0.0482, r = 0.4162). While TD-PD showed decreased FC in the left insula as well as bilateral anterior cingulate gyrus when compared with HCs, and the FC value of the rFIC-left insula was positively correlated with its Hamilton Depression Rating Scale score (p = 0.02, r = 0.50).

Conclusion: The functional connectivity mode of rFIC in AR-PD differed from that in TD-PD. The decreased rFIC FC with the other nodes of salience network might be a potential indicator for AR-PD patients prone to develop cognitive decline and depressive symptoms.
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http://dx.doi.org/10.1007/s10072-020-04917-1DOI Listing
November 2020

Incidence of cerebrovascular disease as a comorbidity in patients with COVID-19: A meta-analysis.

Aging (Albany NY) 2020 11 23;12(23):23450-23463. Epub 2020 Nov 23.

Department of Neurosurgery, Clinical Medical College of Yangzhou University, Yangzhou 225001, Jiangsu, China.

It is essential to know whether COVID-19 patients have a history of cerebrovascular disease, as it may be predictive of prognosis and useful for allocation of limited medical resources. This meta-analysis was performed to assess the incidence of cerebrovascular disease as a comorbidity in COVID-19 patients. The PubMed, Cochrane Library, Embase, CNKI, WFSD, and VIP databases were systematically searched. The pooled analysis of relevant data was conducted using RevMan 5.3 software. The primary outcome was incidence of cerebrovascular disease as a comorbidity. Forty-seven studies involving 16,143 COVID-19 patients were included in this analysis. The incidences of a history of cerebrovascular disease and hypertension in COVID-19 patients were estimated to be 3.0% (95% CI, 2.0%-4.0%; P<0.00001) and 23.0% (95% CI, 16.0%-29.0%; P<0.00001), respectively. The incidence of dizziness/headache as the first symptom in COVID-19 patients was estimated to be 14.0% (95% CI, 8.0%-20.0%; P<0.00001). Subgroup analyses indicated that country, sex ratio, and sample size are potential influencing factors affecting the incidences of cerebrovascular disease, hypertension, and dizziness/headache. These findings suggest that cerebrovascular disease is an underlying comorbidity among patients with COVID-19. In addition, patients experiencing dizziness/headache as the first symptom of COVID-19 should receive a neurological examination.
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http://dx.doi.org/10.18632/aging.104086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7762481PMC
November 2020