Publications by authors named "Lu Song"

245 Publications

A novel G1202A mutation in a Chinese patient with pure adrenomyeloneuropathy and literature review.

Genes Dis 2021 Sep 28;8(5):709-714. Epub 2020 Jan 28.

Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, PR China.

Adrenomyeloneuropathy (AMN) is a kind of varied disease caused by gene mutation and characterized by very-long-chain fatty acids (VLCFA) accumulation. It is diagnosed by clinical features, high VLCFAs levels and gene mutation. AMN is rarely reported in Chinese population. In this study, we report the genetic and clinical features of a Chinese pure AMN patient. Meanwhile, we conducted a literature review of AMN cases to summarize the characteristics of AMN. We report a rare Chinese pure AMN case with slowly progressive weakness of the lower extremities, caused by a novel c.1202G > A mutation in gene. The literature review indicates that spastic paraplegia is the mainly clinical manifestation in patients with AMN. VLCFAs and gene test should be performed in patients with spastic paraplegia of the lower limbs to diagnose AMN.
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http://dx.doi.org/10.1016/j.gendis.2020.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278541PMC
September 2021

Joint analysis of D-dimer, N-terminal pro b-type natriuretic peptide, and cardiac troponin I on predicting acute pulmonary embolism relapse and mortality.

Sci Rep 2021 Jul 21;11(1):14909. Epub 2021 Jul 21.

Department of Respiratory and Critical Care Medicine, Kailuan General Hospital, 57 East Xinhua Rd, Tangshan, Hebei, China.

Previous studies on the adverse events of acute pulmonary embolism (APE) were mostly limited to single marker, and short follow-up duration, from hospitalization to up to 30 days. We aimed to predict the long-term prognosis of patients with APE by joint assessment of D-dimer, N-Terminal Pro-Brain Natriuretic Peptide (NT-ProBNP), and troponin I (cTnI). Newly diagnosed patients of APE from January 2011 to December 2015 were recruited from three hospitals. Medical information of the patients was collected retrospectively by reviewing medical records. Adverse events (APE recurrence and all-cause mortality) of all enrolled patients were followed up via telephone. D-dimer > 0.50 mg/L, NT-ProBNP > 500 pg/mL, and cTnI > 0.40 ng/mL were defined as the abnormal. Kaplan-Meier curve was used to compare the cumulative survival rate between patients with different numbers of abnormal markers. Cox proportional hazard regression model was used to further test the association between numbers of abnormal markers and long-term prognosis of patients with APE after adjusting for potential confounding. During follow-up, APE recurrence and all-cause mortality happened in 78 (30.1%) patients. The proportion of APE recurrence and death in one abnormal marker, two abnormal markers, and three abnormal markers groups were 7.69%, 28.21%, and 64.10% respectively. Patients with three abnormal markers had the lowest survival rate than those with one or two abnormal markers (Log-rank test, P < 0.001). After adjustment, patients with two or three abnormal markers had a significantly higher risk of the total adverse event compared to those with one abnormal marker. The hazard ratios (95% confidence interval) were 6.27 (3.24, 12.12) and 10.7 (4.1, 28.0), respectively. Separate analyses for APE recurrence and all-cause death found similar results. A joint test of abnormal D-dimer, NT-ProBNP, and cTnI in APE patients could better predict the long-term risk of APE recurrence and all-cause mortality.
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http://dx.doi.org/10.1038/s41598-021-94346-7DOI Listing
July 2021

Nucleic Acid Tests for Clinical Translation.

Chem Rev 2021 Jul 13. Epub 2021 Jul 13.

Institute of Molecular Medicine, Department of Liver Surgery, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.

Nucleic acids, including deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), are natural biopolymers composed of nucleotides that store, transmit, and express genetic information. Overexpressed or underexpressed as well as mutated nucleic acids have been implicated in many diseases. Therefore, nucleic acid tests (NATs) are extremely important. Inspired by intracellular DNA replication and RNA transcription, NATs have been extensively developed to improve the detection specificity, sensitivity, and simplicity. The principles of NATs can be in general classified into three categories: nucleic acid hybridization, thermal-cycle or isothermal amplification, and signal amplification. Driven by pressing needs in clinical diagnosis and prevention of infectious diseases, NATs have evolved to be a rapidly advancing field. During the past ten years, an explosive increase of research interest in both basic research and clinical translation has been witnessed. In this review, we aim to provide comprehensive coverage of the progress to analyze nucleic acids, use nucleic acids as recognition probes, construct detection devices based on nucleic acids, and utilize nucleic acids in clinical diagnosis and other important fields. We also discuss the new frontiers in the field and the challenges to be addressed.
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http://dx.doi.org/10.1021/acs.chemrev.1c00241DOI Listing
July 2021

Circulating Growth Differentiation Factor 15 Levels Are Associated With Risk of Both Intracerebral and Subarachnoid Hemorrhage.

Front Neurol 2021 9;12:664010. Epub 2021 Jun 9.

Department of Clinical Sciences, Lund University, Malmö, Sweden.

Growth differentiation factor 15 (GDF-15) has been associated with the risk of developing major bleedings, including but not restricted to intracranial hemorrhages, in patients on oral anticoagulants or dual antiplatelet therapy. We hypothesized that there may be an association of GDF-15 with incidence of hemorrhagic strokes in the general population, which has not been investigated before. Two different case-control studies, one for intracerebral hemorrhage (ICH) and one for subarachnoid hemorrhage (SAH), nested within the population-based Malmö Diet and Cancer cohort, were defined using the incidence density sampling method. GDF-15 was analyzed in frozen blood samples taken at the baseline examination in 1991-1996. The associations between GDF-15 and incident ICH (220 cases, 244 controls) and incident SAH (79 cases, 261 controls), respectively, were explored using conditional logistic regression adjusting for risk factors. GDF-15 levels at baseline were higher in both incident ICH and SAH cases, compared with their respective control subjects. After adjustment for risk factors, significant relationships with high GDF-15 concentrations were observed both for incident ICH (odds ratio (OR) per 1 log2 unit: 2.27, 95% confidence interval (CI): 1.52-3.41; = 7.1 × 10) and incident SAH (OR: 2.16, 95% CI: 1.29-3.59; = 0.0032). High circulating GDF-15 levels were associated with incident ICH and incident SAH, independently of the main risk factors.
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http://dx.doi.org/10.3389/fneur.2021.664010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221424PMC
June 2021

LncRNA CASC2 Alleviates Sepsis-induced Acute Lung Injury by Regulating the miR-152-3p/PDK4 Axis.

Immunol Invest 2021 Jun 24:1-15. Epub 2021 Jun 24.

Department of Intensive Care Unit, Shanxi Provincial People's Hospital, Taiyuan, Shanxi, China.

: Acute lung injury (ALI) is an early complication of sepsis and it is also considered as an important cause of high mortality in sepsis patients. This research aimed to explore the potential role and mechanism of long non-coding RNA (lncRNA) cancer susceptibility candidate 2 (CASC2) in sepsis-induced ALI. : The levels of CASC2, microRNA-152-3p (miR-152-3p) and pyruvate dehydrogenase kinase 4 (PDK4) in sepsis patients and LPS-treated HPAEpiC were detected by quantitative real-time PCR and western blot. Cell viability and apoptosis were assessed by Counting Kit-8 (CCK-8) assay and flow cytometry. The concentrations of inflammatory factors were tested by Enzyme-linked immunosorbent assay. Oxidative stress was evaluated by the levels of reactive oxygen species and superoxide dismutase using corresponding commercial kits. The targeting relationship between miR-152-3p and CASC2 or PDK4 was verified by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays.: CASC2 and PDK4 were down-regulated, while miR-152-3p was up-regulated in sepsis patients and LPS-stimulated HPAEpiC. Overexpression of CASC2 relieved the LPS-resulted cell viability inhibition, apoptosis promotion, inflammatory and oxidative damages in HPAEpiC. In addition, miR-152-3p was a miRNA target of CASC2 and CASC2 alleviated cell injury in LPS-disposed HPAEpiC by sponging miR-152-3p. Moreover, miR-152-3p directly targeted PDK4 and CASC2 increased the PDK4 expression by depending on the sponge effect on miR-152-3p. Meanwhile, inhibition of miR-152-3p attenuated LPS-triggered HPAEpiC injury by upregulating the level of PDK4.: These results suggested that CASC2 ameliorated the LPS-induced injury in HPAEpiC via regulating miR-152-3p/PDK4 pathway.
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http://dx.doi.org/10.1080/08820139.2021.1928693DOI Listing
June 2021

Investigation of the Mechanism of Complement System in Diabetic Nephropathy via Bioinformatics Analysis.

J Diabetes Res 2021 24;2021:5546199. Epub 2021 May 24.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072 Sichuan, China.

Objectives: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) throughout the world, and the identification of novel biomarkers via bioinformatics analysis could provide research foundation for future experimental verification and large-group cohort in DN models and patients.

Methods: GSE30528, GSE47183, and GSE104948 were downloaded from Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs). The difference of gene expression between normal renal tissues and DN renal tissues was firstly screened by GEO2R. Then, the protein-protein interactions (PPIs) of DEGs were performed by STRING database, the result was integrated and visualized via applying Cytoscape software, and the hub genes in this PPI network were selected by MCODE and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to determine the molecular mechanisms of DEGs involved in the progression of DN. Finally, the Nephroseq v5 online platform was used to explore the correlation between hub genes and clinical features of DN.

Results: There were 64 DEGs, and 32 hub genes were identified, enriched pathways of hub genes involved in several functions and expression pathways, such as complement binding, extracellular matrix structural constituent, complement cascade related pathways, and ECM proteoglycans. The correlation analysis and subgroup analysis of 7 complement cascade-related hub genes and the clinical characteristics of DN showed that C1QA, C1QB, C3, CFB, ITGB2, VSIG4, and CLU may participate in the development of DN.

Conclusions: We confirmed that the complement cascade-related hub genes may be the novel biomarkers for DN early diagnosis and targeted treatment.
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http://dx.doi.org/10.1155/2021/5546199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169258PMC
May 2021

MICAL2PV suppresses the formation of tunneling nanotubes and modulates mitochondrial trafficking.

EMBO Rep 2021 Jul 6;22(7):e52006. Epub 2021 Jun 6.

Department of Neurology, Center for Genetic Medicine, Lurie Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Tunneling nanotubes (TNTs) are actin-rich structures that connect two or more cells and mediate cargo exchange between spatially separated cells. TNTs transport signaling molecules, vesicles, organelles, and even pathogens. However, the molecular mechanisms regulating TNT formation remain unclear and little is known about the endogenous mechanisms suppressing TNT formation in lung cancer cells. Here, we report that MICAL2PV, a splicing isoform of the neuronal guidance gene MICAL2, is a novel TNT regulator that suppresses TNT formation and modulates mitochondrial distribution. MICAL2PV interacts with mitochondrial Rho GTPase Miro2 and regulates subcellular mitochondrial trafficking. Moreover, down-regulation of MICAL2PV enhances survival of cells treated with chemotherapeutical drugs. The monooxygenase (MO) domain of MICAL2PV is required for its activity to inhibit TNT formation by depolymerizing F-actin. Our data demonstrate a previously unrecognized function of MICAL2 in TNT formation and mitochondrial trafficking. Furthermore, our study uncovers a role of the MICAL2PV-Miro2 axis in mitochondrial trafficking, providing a mechanistic explanation for MICAL2PV activity in suppressing TNT formation and in modulating mitochondrial subcellular distribution.
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http://dx.doi.org/10.15252/embr.202052006DOI Listing
July 2021

The p75 neurotrophin receptor as a novel intermediate in L-dopa-induced dyskinesia in experimental Parkinson's disease.

Exp Neurol 2021 Aug 7;342:113740. Epub 2021 May 7.

Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200082, China. Electronic address:

In Parkinson's disease (PD), long-term administration of L-dopa often leads to L-dopa-induced dyskinesia (LID), a debilitating motor complication. The p75 neurotrophin receptor (p75NTR) is likely to play a critical role in the regulation of dendritic spine density and morphology and appears to be associated with neuroinflammation, which previously has been identified as a crucial mechanism in LID. While aberrant modifications of p75NTR in neurological diseases have been extensively documented, only a few studies report p75NTR dysfunction in PD, and no data are available in LID. Here, we explored the functional role of p75NTR in LID. In LID rats, we identified that p75NTR was significantly increased in the lesioned striatum. In 6-hydroxydopamine (6-OHDA)-hemilesioned rats, specific knockdown of striatal p75NTR levels achieved by viral vector injection into the striatum prevented the development of LID and increased striatal structural plasticity. By contrast, we found that in 6-OHDA-hemilesioned rats, striatal p75NTR overexpression exacerbated LID and facilitated striatal dendritic spine losses. Moreover, we observed that the immunomodulatory drug fingolimod attenuated LID without lessening the therapeutic efficacy of L-dopa and normalized p75NTR levels. Together, these data demonstrate for the first time that p75NTR plays a pivotal role in the development of LID and that p75NTR may act as a potential novel target for the management of LID.
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http://dx.doi.org/10.1016/j.expneurol.2021.113740DOI Listing
August 2021

Bioaerosol is an important transmission route of antibiotic resistance genes in pig farms.

Environ Int 2021 09 14;154:106559. Epub 2021 Apr 14.

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

Although pig farms are hotspots of antibiotic resistance due to intensive use of antibiotics, little is known about the abundance, diversity and transmission of airborne antibiotic resistance genes (ARGs). This study reports that bioaerosol is an important spread route of ARGs in pig farms. ARGs, mobile genetic elements (MGEs), and bacterial communities were investigated in both air and feces samples during winter and summer. The average concentration of airborne ARGs and MGEs during winter is higher than that during summer when using the ventilation system. The tetM is identified as the predominant airborne ARG with abundance of 6.3 ± 1.2 log copies/m. Clostridium and Streptococcus are two dominant bacteria and several opportunistic pathogens are detected in air samples. High temperature is favorable for more diverse bacterial communities, but relative humidity has negative effects. The wind speed promotes the spread of airborne ARGs. The network analysis results show the average fecal contribution to airborne bacteria is 19.9% and 59.4% during summer and winter, respectively. Horizontal gene transfer plays an important role in the dissemination of airborne ARGs during winter (77.8% possibility), while a lower possibility of 12.0% in summer.
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http://dx.doi.org/10.1016/j.envint.2021.106559DOI Listing
September 2021

Microscopic Afterglow Bioimaging by Ultralong Organic Phosphorescent Nanoparticles in Living Cells and Zebrafish.

Anal Chem 2021 04 14;93(16):6516-6522. Epub 2021 Apr 14.

Key Laboratory of Flexible Electronics (KLOFE) and Institute of Advanced Materials (IAM), Nanjing Tech University (NanjingTech), 30 South Puzhu Road, Nanjing 211816, China.

Compared with short-lived emission probes featuring fluorescence imaging , the use of phosphorescent probes imparts the advantage of long-lived signal persistence that distinguishes against background fluorescence interference. However, the realization of ultralong organic phosphorescent (UOP) probes with an ultralong emission lifetime in an aqueous medium is still a challenge. Here, we present a rational strategy for obtaining UOP nanoparticles (NPs) in an air-saturated aqueous medium prepared using an organic phosphor (PDBCz) and a surfactant polymer (PVP), named [email protected], showing an ultralong emission lifetime of 284.59 ms and a phosphorescence quantum efficiency of 7.6%. The excellent phosphorescence properties and water solubility of [email protected] make it a promising candidate for biological imaging. The as-prepared [email protected] NPs possess excellent luminescence intensity as well as illustrious biocompatibility both in vitro and in vivo. We demonstrate their use as an efficient phosphorescent nanoprobe both in living cells and zebrafish by capturing their afterglow emission signals under microscopy observation for the first time, realizing convenient and fast bioimaging with low cost, which allows for anti-fluorescence interference and shows promise for the future theragnostic applications in nanomedicine.
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http://dx.doi.org/10.1021/acs.analchem.1c00423DOI Listing
April 2021

Reaching the Full Potential of Electroorganic Synthesis by Paired Electrolysis.

Chem Rec 2021 Apr 9. Epub 2021 Apr 9.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, School of Chemical Science, University of Chinese Academy of Sciences, Beijing, 100049, China.

Electroorganic synthesis has recently become a rapidly blossoming research area within the organic synthesis community. It should be noted that electrochemical reaction is always a balanced reaction system with two half-cell reactions-oxidation and reduction. Most electrochemical strategies, however, typically focus on one of the two sides for the desired transformations. Paired electrolysis has two desirable half reactions running simultaneously, thus maximizing the overall margin of atom and energy economy. Meanwhile, the spatial separation between oxidation and reduction is the essential feature of electrochemistry, offering unique opportunities for the development of redox-neutral reactions that would otherwise be challenging to accomplish in a conventional reaction flask setting. This review discusses the most recent illustrative examples of paired electrolysis with special emphasis on sequential and convergent processes.
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http://dx.doi.org/10.1002/tcr.202100025DOI Listing
April 2021

Acupuncture and related therapies for poststroke insomnia: A protocol for systematic review and network meta-analysis.

Medicine (Baltimore) 2021 Mar;100(9):e25039

Huangshi Traditional Chinese Medicine Hospital, Huangshi, Hubei, China.

Objective: To compare and evaluate the clinical effects on patients with poststroke insomnia of various acupuncture and acupuncture-related therapies.

Methods: In order to analyze the direct and indirect evidence from related studies, we used network meta-analysis (NMA). In order to collect randomized controlled trials (RCTs) of acupuncture and related therapies in the treatment of poststroke insomnia, 3 English and 4 Chinese databases were searched. After 2 researchers independently screened the literature, extracted the information, and assessed the probability of bias in the included studies, the data was analyzed using Stata15.0 and WinBUGS1.4.3 software.

Results: Based on the existing data, the pros and cons of different acupuncture-related therapies are compared extensively, the effectiveness of different acupuncture-related therapies is ranked compared to drugs with hypnotic effect in poststroke insomnia care, and the best methods or combinations of acupuncture intervention are summarized.

Conclusion: This study will provide new evidence for the safety and effectiveness of acupuncture-related therapies in the treatment of poststroke insomnia, and may be helpful for clinicians, poststroke insomnia patients, and clinical guideline makers to choose the optimal combination of acupuncture for the treatment of poststroke insomnia.

Registration Number: INPLASY202120028.
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http://dx.doi.org/10.1097/MD.0000000000025039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939198PMC
March 2021

Circular RNA circVMA21 ameliorates lipopolysaccharide (LPS)-induced acute kidney injury by targeting the miR-199a-5p/NRP1 axis in sepsis.

Biochem Biophys Res Commun 2021 Apr 26;548:174-181. Epub 2021 Feb 26.

Department of Intensive Medicine, Shanxi Provincial Peoples Hospital, Taiyuan City, Shanxi Province, China.

Background: Sepsis is a serious and elusive syndrome caused by infection, with high mortality worldwide. Circular RNAs vacuolar ATPase assembly factor (circVMA21) has been reported to be related to the inflammatory damages in sepsis. This study is designed to explore the role and mechanism of circVMA21 in the lipopolysaccharide (LPS)-induced cell injury in sepsis.

Methods: Cell viability and apoptosis were detected by CCK-8, and flow cytometry assays. CircVMA21, microRNA-199a-5p (miR-199a-5p), and Neuropilin-1 (NRP1) level were determined by RT-qPCR. Protein levels of Bcl-2, Bax, cleaved-caspase 3, and NRP1 were examined by Western blot assay. IL-1β, IL-6, and TNF-α were detected using ELISA. Superoxide Dismutase (SOD) and glutathione (GSH) were measured by the special kits. The binding relationship between miR-199a-5p and circVMA21 or NRP1 was predicted by Starbase 3.0 and then verified by a dual-luciferase reporter and RIP assays.

Results: CircVMA21 and NRP1 were decreased, and miR-199a-5p was increased in LPS-induced THP-1 cells. Moreover, circVMA21 overexpression could repress LPS-mediated cell viability, apoptosis, inflammation, and oxidative stress in THP-1 cells. The mechanical analysis suggested that circVMA21 regulated NRP1 expression through sponging miR-199a-5p.

Conclusion: CircVMA21 upregulation could attenuate LPS-triggered THP-1 cell injury through modulating the miR-199a-5p/NRP1 axis, hinting an underlying therapeutic strategy for sepsis patients.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.028DOI Listing
April 2021

Based on Network Pharmacology Tools to Investigate the Molecular Mechanism of Cordyceps sinensis on the Treatment of Diabetic Nephropathy.

J Diabetes Res 2021 5;2021:8891093. Epub 2021 Feb 5.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, 610072 Sichuan, China.

Background: Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus and is a major cause of end-stage kidney disease. Cordyceps sinensis (Cordyceps, Dong Chong Xia Cao) is a widely applied ingredient for treating patients with DN in China, while the molecular mechanisms remain unclear. This study is aimed at revealing the therapeutic mechanisms of Cordyceps in DN by undertaking a network pharmacology analysis.

Materials And Methods: In this study, active ingredients and associated target proteins of Cordyceps sinensis were obtained via Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Swiss Target Prediction platform, then reconfirmed by using PubChem databases. The collection of DN-related target genes was based on DisGeNET and GeneCards databases. A DN-Cordyceps common target interaction network was carried out via the STRING database, and the results were integrated and visualized by utilizing Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to determine the molecular mechanisms and therapeutic effects of Cordyceps on the treatment of DN.

Results: Seven active ingredients were screened from Cordyceps, 293 putative target genes were identified, and 85 overlapping targets matched with DN were considered potential therapeutic targets, such as TNF, MAPK1, EGFR, ACE, and CASP3. The results of GO and KEGG analyses revealed that hub targets mainly participated in the AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, PI3K-Akt signaling pathway, and IL-17 signaling pathway. These targets were correlated with inflammatory response, apoptosis, oxidative stress, insulin resistance, and other biological processes.

Conclusions: Our study showed that Cordyceps is characterized as multicomponent, multitarget, and multichannel. Cordyceps may play a crucial role in the treatment of DN by targeting TNF, MAPK1, EGFR, ACE, and CASP3 signaling and involved in the inflammatory response, apoptosis, oxidative stress, and insulin resistance.
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http://dx.doi.org/10.1155/2021/8891093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884116PMC
February 2021

Systemic Inflammation Increases the Susceptibility to Levodopa-Induced Dyskinesia in 6-OHDA Lesioned Rats by Targeting the NR2B-Medicated PKC/MEK/ERK Pathway.

Front Aging Neurosci 2020 1;12:625166. Epub 2021 Feb 1.

Department of Neurology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The long-term administration of levodopa (L-dopa), the gold-standard treatment for Parkinson's disease (PD), is irreparably associated with L-dopa-induced dyskinesia (LID), which dramatically affects the quality of life of patients. However, the underlying molecular mechanisms of how LID exacerbates remain unknown. Neuroinflammation in the striatum plays an active role in LID. These findings prompt an investigation of non-neuronal mechanisms of LID. This study will examine the effects of systemic inflammation in the development and progression of LID. To evaluate the possible influence of systemic inflammation in the appearance of LID, the PD rats received an intraperitoneal (IP) injection of various concentrations of lipopolysaccharides (LPS, 1, 2, and 5 mg/kg) or saline. One day later, these PD rats started to receive daily treatment with L-dopa (6 mg/kg) along with benserazide (6 mg/kg) or saline for 21 days, and dyskinesia was evaluated at several time points. Moreover, the activation of microglia and astrocytes and the molecular changes in NR2B and mGLUR5 signaling pathways were measured. We found that systemic inflammatory stimulation with LPS exacerbated the intensity of abnormal involuntary movements (AIMs) induced by L-dopa treatment in 6-hydroxydopamine (6-OHDA) lesioned rats. The LPS injection activated the gliocytes and increased the levels of proinflammatory cytokines in the striatum in LID rats. The PD rats that received the LPS injection showed the overexpression of p-NR2B and NR2B, as well as activated PKC/MEK/ERK and NF-κB signal pathways in response to the L-dopa administration. On the contrary, clodronate-encapsulated liposomes (Clo-lipo), which could suppress the inflammatory response induced by peripheral LPS injection, improved behavioral dysfunction, inhibited neuroinflammation, prevented NR2B overexpression, and decreased the phosphorylation of PKC/MEK/ERK and NF-κB signaling pathways. This study suggests that systemic inflammation, by exacerbating preexisting neuroinflammation and facilitating NR2B subunit activity, may play a crucial role in the development of LID. The administration of Clo-lipo restores the effects of LPS and decreases the susceptibility to LID in 6-OHDA lesioned rats.
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http://dx.doi.org/10.3389/fnagi.2020.625166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882708PMC
February 2021

A fatal outcome from SARS-CoV-2 infection: One case report of a young man with multiple organ damage.

Radiol Infect Dis 2020 Dec 31;7(4):208-212. Epub 2020 Jul 31.

Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.

The coronavirus disease 2019 (COVID-19) first emerged in Wuhan, China on December 2019 and has become a severe public health issue worldwide. A 36-year-old man was presented to the hospital staff with a fever that had already persisted for a three-day period, general weakness and diarrhea. He had no chronic diseases and was tested positive for COVID-19 with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid. During his hospitalization, several abnormal indicators appeared in his laboratory tests, which implied systemic inflammation and multiple organ damage. A series of chest radiographs monitored the dynamic process of lung lesions, which could predict the clinical changes of the patient. His condition deteriorated rapidly, resulting in death due to acute respiratory distress syndrome (ARDS) on hospital day 13. The case indicates that inflammatory response may appear in people infected with SARS-CoV-2 and may lead to multiple organ damage (especially pancreatic damage). When a COVID-19 patient is entering into the critical stage, their condition could rapidly deteriorate.
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http://dx.doi.org/10.1016/j.jrid.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834659PMC
December 2020

Aerosol transmission, an indispensable route of COVID-19 spread: case study of a department-store cluster.

Front Environ Sci Eng 2021 25;15(3):46. Epub 2020 Dec 25.

Tianjin Centers for Disease Control and Prevention, Tianjin, 300350 China.

Patients with COVID-19 have revealed a massive outbreak around the world, leading to widespread concerns in global scope. Figuring out the transmission route of COVID-19 is necessary to control further spread. We analyzed the data of 43 patients in Baodi Department Store (China) to supplement the transmission route and epidemiological characteristics of COVID-19 in a cluster outbreak. Incubation median was estimated to endure 5.95 days (2-13 days). Almost 76.3% of patients sought medical attention immediately uponillness onset. The median period ofillness onsetto hospitalization and confirmation were 3.96 days (0-14) and 5.58 days (1-21), respectively. Patients with different cluster case could demonstrate unique epidemiological characteristics due to the particularity of outbreak sites. SRAS-CoV-2 can be released into the surrounding air through patient's respiratory tract activities, and can exist for a long time for long-distance transportation. SRAS-CoV-2 RNA can be detected in aerosol in different sites, including isolation ward, general ward, outdoor, toilet, hallway, and crowded public area. Environmental factors influencing were analyzed and indicated that the SARS-CoV-2 transportation in aerosol was dependent on temperature, air humidity, ventilation rate and inactivating chemicals (ozone) content. As for the infection route of case numbers 2 to 6, 10, 13, 16, 17, 18, 20 and 23, we believe that aerosol transmission played a significant role in analyzing their exposure history and environmental conditions in Baodi Department Store. Aerosol transmission could occur in some cluster cases when the environmental factors are suitable, and it is an indispensable route of COVID-19 spread.
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http://dx.doi.org/10.1007/s11783-021-1386-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771204PMC
December 2020

The first mitochondrial genome from the Sterrhinae (Lepidoptera: Geometridae) and its phylogenetic implications.

Mitochondrial DNA B Resour 2019 Dec 12;5(1):214-215. Epub 2019 Dec 12.

College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, Henan, China.

In this study, the complete mitochondrial genome of a geometrid species, (Prout), was sequenced. The mitogenome is a circular, double-stranded molecule, with 15,950 bp in size. The typical 37 mitochondrial genes (13 PCGs, 22 tRNAs, and 2 rRNAs) and an A + T-rich region are included. Gene content and arrangement are highly conserved and typical of Lepidoptera. Interestingly, the mitogenome is rich in microsatellite sequences of (TA) with a scattered distribution in six intergenic regions. Phylogenetic analyses based on the combined 37 mitochondrial genes show that the Larentiinae and Ennominae are monophyletic. The Sterrhinae, which is represented by the only sequenced in this study, shows a closer relationship with the Larentiinae than Ennominae, which confirms previous morphological studies.
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http://dx.doi.org/10.1080/23802359.2019.1699467DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748674PMC
December 2019

Complete mitochondrial genome of the (Lepidoptera: Geometridae) and its phylogenetic implications.

Mitochondrial DNA B Resour 2019 Nov 20;4(2):4142-4143. Epub 2019 Nov 20.

College of Life Science and Agronomy, Zhoukou Normal University, Zhoukou, PR China.

In this study, the complete mitochondrial genome of (Mabille) was sequenced and its phylogenetic implications were investigated. The mitogenome is a circular, double-stranded molecule, with 15,602 bp in length. The typical 37 mitochondrial genes (13 protein-coding genes (PCGs), 22 tRNAs, and 2 rRNAs) and an A + T-rich region are included. Gene content and arrangement are highly conserved and typical of Lepidoptera. Phylogenetic analyses based on the combined 37 mitochondrial genes consistently recovered the Larentiinae and Ennominae involved are reciprocally monophyletic with the highest supports. The was clustered with other two members of the Larentiinae, reinforcing that of previous morphological studies.
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http://dx.doi.org/10.1080/23802359.2019.1692725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707744PMC
November 2019

TLR9 Rs352140 polymorphism contributes to a decreased risk of bacterial meningitis: evidence from a meta-analysis.

Epidemiol Infect 2020 11 4;148:e294. Epub 2020 Nov 4.

Department of Critical Care Medicine, Sichuan Cancer Hospital & Institute, Chengdu610041, People's Republic of China.

Some studies have suggested that the Toll-like receptor 9 polymorphism (TLR9 rs352140) is closely related to the risk of bacterial meningitis (BM), but this is subject to controversy. This study set out to estimate whether the TLR9 rs352140 polymorphism confers an increased risk of BM. Relevant literature databases were searched including PubMed, Embase, the Cochrane Library and China National Knowledge Infrastructure (CNKI) up to August 2020. Seven case-control studies from four publications were enrolled in the present meta-analysis. Odds ratios (OR) and confidence intervals (95% CI) were calculated to estimate associations between BM risk and the target polymorphism. Significant associations identified were allele contrast (A vs. G: OR 0.66, 95% CI 0.59-0.75, P = 0.000), homozygote comparison (AA vs. AG/GG: OR 0.62, 95% CI 0.49-0.78, P = 0.000), heterozygote comparison (A vs. G: OR 0.74, 95% CI 0.61-0.91, P = 0.005), recessive genetic model (AA vs. AG/GG: OR 0.78, 95% CI 0.65-0.93, P = 0.006) and dominant genetic model (AA vs. AG/GG: OR 0.70, 95% CI 0.57-0.85, P = 0.000). The findings indicate that, in contrast to some studies, the TLR9 rs352140 polymorphism is associated with a decreased risk for BM.
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http://dx.doi.org/10.1017/S0950268820002666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7770465PMC
November 2020

Illuminating single genomic loci in live cells by reducing nuclear background fluorescence.

Sci China Life Sci 2021 May 26;64(5):667-677. Epub 2020 Oct 26.

National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.

The tagging of genomic loci in living cells provides visual evidence for the study of genomic spatial organization and gene interaction. CRISPR/dCas9 (clustered regularly interspaced short palindromic repeats/deactivated Cas9) labeling system labels genes through binding of the dCas9/sgRNA/fluorescent protein complex to repeat sequences in the target genomic loci. However, the existence of numerous fluorescent proteins in the nucleus usually causes a high background fluorescent readout. This study aims to limit the number of fluorescent modules entering the nucleus by redesigning the current CRISPR/dCas9-SunTag labeling system consisting of dCas9-SunTag-NLS (target module) and scFv-sfGFP-NLS (signal module). We removed the nuclear location sequence (NLS) of the signal module and inserted two copies of EGFP into the signal module. The ratio of the fluorescent intensity of the nucleus to that of the cytoplasm (N/C ratio) was decreased by 71%, and the ratio of the signal to the background (S/B ratio) was increased by 1.6 times. The system can stably label randomly selected genomic loci with as few as 9 repeat sequences.
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http://dx.doi.org/10.1007/s11427-020-1794-2DOI Listing
May 2021

USP6NL mediated by LINC00689/miR-142-3p promotes the development of triple-negative breast cancer.

BMC Cancer 2020 Oct 14;20(1):998. Epub 2020 Oct 14.

Department of Breast Surgery, Taian City Central Hospital, Taian, 271000, Shandong, China.

Background: Triple-negative breast cancer (TNBC), in part because of the high metastasis rate, is one of the most prevalent causes of malignancy-related mortality globally. Ubiquitin specific peptidase 6 N-terminal like (USP6NL) has been unmasked to be implicated in some human cancers. However, the precise biological function of USP6NL in TNBC has not been defined.

Methods: RNA expression was examined by real-time quantitative PCR (RT-qPCR), while USP6NL protein level was tested through western blot. Besides, cell proliferation was assessed by using colony formation assay, whereas cell apoptosis estimated by flow cytometry analysis, JC-1 assay and TUNEL assay. Transwell assays were adopted to detect the migration and invasion of indicated TNBC cells. Immunofluorescence (IF) assay evaluated epithelial-mesenchymal transitions (EMT) progress in TNBC. Further, RNA immunoprecipitation (RIP), RNA pull down and luciferase reporter assays were implemented for measuring the mutual interplay among USP6NL, miR-142-3p and long intergenic non-protein coding RNA 689 (LINC00689).

Results: Elevated USP6NL level was uncovered in TNBC cells. RNA interference-mediated knockdown of USP6NL inhibited TNBC cell growth, motility and EMT. Further, USP6NL was proved as the target of a tumor-inhibitor miR-142-3p, and LINC00689 augmented USP6NL expression by absorbing miR-142-3p. Importantly, miR-142-3p deficiency or USP6NL overexpression fully abolished the inhibitory effect of LINC00689 silence on TNBC cellular behaviors.

Conclusion: All data revealed the important role of USP6NL/LINC00689/miR-142-3p signaling in TNBC. The findings might provide a new and promising therapeutic biomarker for treating patients with TNBC.
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http://dx.doi.org/10.1186/s12885-020-07394-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559130PMC
October 2020

Elevated Troponin Results in a Patient on Immunotherapy for Crohn's Disease.

J Appl Lab Med 2021 Mar;6(2):554-559

Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA.

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http://dx.doi.org/10.1093/jalm/jfaa088DOI Listing
March 2021

Strain localisation and failure at twin-boundary complexions in nickel-based superalloys.

Nat Commun 2020 09 29;11(1):4890. Epub 2020 Sep 29.

School of Materials, University of Manchester, M13 9PL, Manchester, UK.

Twin boundaries (TBs) in Ni-based superalloys are vulnerable sites for failure in demanding environments, and a current lack of mechanistic understanding hampers the reliable lifetime prediction and performance optimisation of these alloys. Here we report the discovery of an unexpected γ″ precipitation mechanism at TBs that takes the responsibility for alloy failure in demanding environments. Using multiscale microstructural and mechanical characterisations (from millimetre down to atomic level) and DFT calculations, we demonstrate that abnormal γ″ precipitation along TBs accounts for the premature dislocation activities and pronounced strain localisation associated with TBs during mechanical loading, which serves as a precursor for crack initiation. We clarify the physical origin of the TBs-related cracking at the atomic level of γ″-strengthened Ni-based superalloys in a hydrogen containing environment, and provide practical methods to mitigate the adverse effect of TBs on the performance of these alloys.
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http://dx.doi.org/10.1038/s41467-020-18641-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524752PMC
September 2020

Leptin, Obesity, and Hypertension: A Review of Pathogenetic Mechanisms.

Metab Syndr Relat Disord 2020 11 1;18(9):399-405. Epub 2020 Sep 1.

Department of Medical Sciences, Frank H. Netter School of Medicine, NH-MED, Quinnipiac University, Hamden, Connecticut, USA.

The adipokine leptin is expressed at higher concentrations in obese subjects, who also incidentally have a higher prevalence of hypertension. The pathogenesis of this obesity-related hypertension is controversial and is believed to be related to many factors including increased sympathetic activity, abnormalities of the renin-angiotensin system, sodium retention, and an endotheliopathy acting independently or in concert with increased circulating leptin. This review discusses the potential mechanisms through which changes in leptin signal transduction pathways in tissues with the leptin receptor, especially the hypothalamus, mediate the pathogenetic relationships between obesity and hypertension. The hypothesis is explored that leptin effects on blood pressure (BP) are meditated by the downstream effects of hypothalamic leptin signaling and ultimately result in activation of specific melanocortin receptors located on sympathetic neurons in the spinal cord. The physiological consequences of this sympathetic activation of the heart and kidney are activation of the renin-angiotensin system, sodium retention and circulatory expansion and finally, elevated BP. This sequence of events has been elegantly demonstrated with leptin infusion and gene knockout studies in animal models but has not been convincingly reproducibly confirmed in humans. Further studies in human subjects on the specific roles of hypothalamic leptin in essential hypertension are indicated as elucidation of the signaling pathways should provide better understanding of the role of weight loss in BP control and afford an additional mechanism for pharmacologic control of BP in adults and children at risk of cardiovascular disease.
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http://dx.doi.org/10.1089/met.2020.0065DOI Listing
November 2020

CT features of coronavirus disease 2019 (COVID-19) in the original district of this disease (Wuhan): a pictorial review.

Radiol Infect Dis 2020 Sep 30;7(3):91-96. Epub 2020 Jul 30.

Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.

On December 31, 2019, the Wuhan Health Commission reported the discovery of an "unexplained" pneumonia for the first time; the pathogen was confirmed as novel coronavirus pneumonia (2019-nCoV) on January 7, 2020. As one of the important examination methods for the Corona Virus Disease 2019 (COVID-19), Computed Tomography (CT) examination plays an important role in the clinical discovery of suspected cases, diagnosis, and treatment review. This paper reviews the published papers in order to offer help in early clinical screening, disease diagnosis, disease severity determination and post-treatment review.
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http://dx.doi.org/10.1016/j.jrid.2020.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392110PMC
September 2020

Experimental and Density Functional Theory Studies on 1,1,1,4,4,4-Hexafluoro-2-Butene Pyrolysis.

Molecules 2020 Aug 21;25(17). Epub 2020 Aug 21.

State Key Laboratory of Fire Science, University of Science and Technology of China, Hefei 230027, China.

A series of thermal decomposition experiments were conducted over a temperature range of 873-1073 K to evaluate the thermal stability of 1,1,1,4,4,4-hexafluoro-2-butene (HFO-1336mzz(Z)) and the production of hydrogen fluoride (HF). According to the detected products and experimental phenomena, the thermal decomposition of HFO-1336mzz(Z) could be divided into three stages. Our experimental results showed that HF concentration gradually increased with the elevation of thermal decomposition temperature. In this present study, a total of seven chemical reaction pathways of HFO-1336mzz(Z) pyrolysis were proposed to explore the generated mechanism on products through density functional theory (DFT) with M06-2X/6-311++(d,p) level theory. The thermal decomposition mechanism of pure HFO-1336mzz(Z) was discussed and the possible formation pathways of HF and other main products were proposed.
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http://dx.doi.org/10.3390/molecules25173799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7503914PMC
August 2020

Analysis of prediction and early warning indexes of patients with COVID-19.

Expert Rev Respir Med 2020 12 23;14(12):1257-1260. Epub 2020 Jul 23.

Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Shanxi Medical University , Taiyuan, China.

Background: The aim was to compare the laboratory data of patients with suspected and confirmed new coronavirus pneumonia (COVID-19) and look for diagnostic predictive and early warning indicators, which will help to better manage the disease.

Methods: A total of 36 confirmed COVID-19 patients were divided into the general (n = 17) and critical group (n = 19). The suspected group enrolled 23 suspected COVID-19 patients with the negative nucleic acid test result. We collected all patients' clinical characteristics and some laboratory indicators at the time of admission and conducted Logistic regression analysis after comparing the differences between groups.

Results: There were no significant differences in age, gender, disease duration, fever history, and comorbidities between the suspected and general group (P > 0.05); however, fibrinogen was statistically different (P < 0.05). Compared with the general group, the oxygenation index and lymphocytes were significantly reduced and the Neutrophil-to-lymphocyte Ratio (NLR) and total bilirubin were increased in the critical group (P < 0.05). The fibrinogen OR value was 2.52 (95% CI 1.18-5.36, P = 0.017) and the NLR OR value was 2.91 (95% CI 1.36-6.21, P = 0.006).

Conclusions: Fibrinogen is a valuable diagnostic predictor for patients with suspected COVID-19. For confirmed COVID-19 patients, the NLR is a valuable early warning indicator.
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http://dx.doi.org/10.1080/17476348.2020.1793674DOI Listing
December 2020