Publications by authors named "Ke Ma"

568 Publications

Electrospun PCL/MoS Nanofiber Membranes Combined with NIR-Triggered Photothermal Therapy to Accelerate Bone Regeneration.

Small 2021 Oct 13:e2104747. Epub 2021 Oct 13.

Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, China.

Electrospun nanofiber membranes have been widely used for guided bone regeneration (GBR). For assistance in bone healing, photothermal therapy which renders moderate heat stimulation to defect regions by near-infrared (NIR) light irradiation has attracted much attention in recent years. Combined with photothermal therapy, novel electrospun poly(ε-caprolactone)/molybdenum disulfide (PCL/MoS ) nanofiber membranes are innovatively synthesized as GBR for bone therapy, wherein the exfoliated MoS nanosheets served as osteogenic enhancers and NIR photothermal agents. With the doping of MoS , the mechanical properties of nanofiber membranes got improved with the degradation unaffected. The composite PCL/MoS membranes show enhanced cell growth and osteogenic performance compared with PCL alone. Under NIR-triggered mild photothermal therapy, osteogenesis and bone healing are accelerated by using PCL/MoS nanofiber membranes for growth of bone mesenchymal stem cells in vitro and repair of rat tibia bone defect in vivo. The novel nanofiber membranes may be developed as intelligent GBR in the therapy of bone defects.
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http://dx.doi.org/10.1002/smll.202104747DOI Listing
October 2021

Application of laser speckle blood perfusion imaging in the evaluation of erectile function in rats.

Andrologia 2021 Oct 4:e14264. Epub 2021 Oct 4.

Department of Urology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Intracavernosal pressure measurement is the gold standard for evaluating erectile function in experimental animals, but it has the shortcoming of being invasive. This study aimed to explore the application of laser speckle perfusion imaging in evaluating erectile function in rats. Sixty Sprague Dawley rats were randomly divided into the sham operation and model groups (n = 30 each). A rat model of neuroinjury erectile dysfunction was established by surgically damaging the bilateral cavernous nerves in the model group. Simulated surgery was performed in the sham operation group; the nerves were not damaged. Erectile function was evaluated by comparing the changes in intracavernosal pressure and blood flow fluctuations when the cavernous nerve was stimulated using the same voltage parameters. Intracavernosal pressure in the model group was significantly lower than that in the other group when using 2.5 V. No significant difference was found in cavernous blood flow fluctuation between the two groups when using 0.5 V. Cavernous blood flow fluctuation in the model group after 2.5 V, 5 V and 7.5 V stimulations was significantly lower than that in the sham operation group. Evaluating erectile function in rats is feasible by measuring the cavernous blood flow using laser speckle perfusion imaging.
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http://dx.doi.org/10.1111/and.14264DOI Listing
October 2021

'First week' is the crucial period for deciding living donor liver transplantation in patients with acute-on-chronic liver failure.

Hepatol Int 2021 Oct 4. Epub 2021 Oct 4.

Department of Hepatology, Cardinal Santos Medical Centre, Manila, Philippines.

Background And Aims: Acute-on-chronic liver failure (ACLF) is a rapidly progressive illness with high short-term mortality. Timely liver transplant (LT) may improve survival. We evaluated various indices for assessment of the severity of liver failure and their application for eligibility and timing of living donor LT (LDLT).

Methods: Altogether 1021 patients were analyzed for the severity and organ failure at admission to determine transplant eligibility and 28 day survival with or without transplant.

Results: The ACLF cohort [mean age 44 ± 12.2 years, males 81%) was of sick patients; 55% willing for LT at admission, though 63% of them were ineligible due to sepsis or organ failure. On day 4, recovery in sepsis and/or organ failure led to an improvement in transplant eligibility from 37% at baseline to 63.7%. Delay in LT up to 7 days led to a higher incidence of multiorgan failure (p < 0.01) contributing to 23% of the first week and 55% of all-cause 28-day mortality. In a matched cohort analysis, the actuarial survival with LT (n = 41) and conditional survival in the absence of transplant (n = 191) were comparable, when the condition, i.e., transplant was adjusted. The comparison curve showed differentiation in survival beyond 7 days (p < 0.01).

Conclusions: ACLF is a rapidly progressive disease and risk stratification within the first week of hospitalization is needed. 'Emergent LT' should be defined in the first week in the ACLF patients; the transplant window for improving survival in a live donor setting.
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http://dx.doi.org/10.1007/s12072-021-10206-6DOI Listing
October 2021

Activation of TMEM16A Ca-activated Cl channels by ROCK1/moesin promotes breast cancer metastasis.

J Adv Res 2021 Nov 17;33:253-264. Epub 2021 Mar 17.

Department of Ion Channel Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, China.

Introduction: Transmembrane protein 16A (TMEM16A) is a Ca-activated chloride channel that plays a role in cancer cell proliferation, migration, invasion, and metastasis. However, whether TMEM16A contributes to breast cancer metastasis remains unknown.

Objective: In this study, we investigated whether TMEM16A channel activation by ROCK1/moesin promotes breast cancer metastasis.

Methods: Wound healing assays and transwell migration and invasion assays were performed to study the migration and invasion of MCF-7 and T47D breast cancer cells. Western blotting was performed to evaluate the protein expression, and whole-cell patch clamp recordings were used to record TMEM16A Cl currents. A mouse model of breast cancer lung metastasis was generated by injecting MCF-7 cells via the tail vein. Metastatic nodules in the lung were assessed by hematoxylin and eosin staining. Lymph node metastasis, overall survival, and metastasis-free survival of breast cancer patients were assessed using immunohistochemistry and The Cancer Genome Atlas dataset.

Results: TMEM16A activation promoted breast cancer cell migration and invasion as well as breast cancer metastasis in mice. Patients with breast cancer who had higher TMEM16A levels showed greater lymph node metastasis and shorter survival. Mechanistically, TMEM16A promoted migration and invasion by activating EGFR/STAT3/ROCK1 signaling, and the role of the TMEM16A channel activity was important in this respect. ROCK1 activation by RhoA enhanced the TMEM16A channel activity via the phosphorylation of moesin at T558. The cooperative action of TMEM16A and ROCK1 was supported through clinical findings indicating that breast cancer patients with high levels of TMEM16A/ROCK1 expression showed greater lymph node metastasis and poor survival.

Conclusion: Our findings revealed a novel mechanism underlying TMEM16A-mediated breast cancer metastasis, in which ROCK1 increased TMEM16A channel activity via moesin phosphorylation and the increase in TMEM16A channel activities promoted cell migration and invasion. TMEM16A inhibition may be a novel strategy for treating breast cancer metastasis.
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http://dx.doi.org/10.1016/j.jare.2021.03.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463928PMC
November 2021

Case Report: Metagenomic Next-Generation Sequencing Confirmed a Case of Central Nervous System Infection With in Non-endemic Areas.

Front Med (Lausanne) 2021 14;8:723197. Epub 2021 Sep 14.

Department of Emergency and Critical Care Medicine, Fudan University Affiliated North Huashan Hospital, Shanghai, China.

Brucellosis is a highly contagious zoonotic disease caused by bacteria that belong to the genus . It is a major endemic disease in northern China. We reported a rare case of central nervous system (CNS) infection caused by in a patient living in non-endemic areas. The medical history of the patient included chronic headache and trunk numbness. Based on the presented clinical symptoms and medical examinations, a clinical diagnosis of binocular uveo-encephalitis was made in the local hospital. The patient's symptoms were unrelieved after being treated with empiric therapy. Soon after, the patient was admitted to our hospital because of the obnubilation and coma in the trip. We ran a few examinations and sent the cerebrospinal fluid (CSF) for metagenomic next-generation sequencing (mNGS) immediately. The Magnetic resonance imaging (MRI) examination was unremarkable, and bilateral mastoid inflammation was attached. Metagenomic next-generation sequencing suggested a CNS infection caused by . Then, the results of the serum agglutination test and quantitative polymerase chain reaction assay also confirmed that. After being treated with doxycycline, rifampin, and cefatriaxone, consciousness of the patient was restored and headache diminished. Two months later, a lumbar puncture was used to check the pressure of the CSF, and the total course of treatment was more than 6 months. This case highlighted the potential value of mNGS in early clinal diagnosis. We believe that mNGS may be a complementary method for rapid identification of infection of CNS caused by the pathogen.
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http://dx.doi.org/10.3389/fmed.2021.723197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476800PMC
September 2021

Reconstitution of biosynthetic pathway for mushroom-derived cyathane diterpenes in yeast and generation of new "non-natural" analogues.

Acta Pharm Sin B 2021 Sep 3;11(9):2945-2956. Epub 2021 May 3.

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

Mushroom-derived cyathane-type diterpenes possess unusual chemical skeleton and diverse bioactivities. To efficiently supply bioactive cyathanes for deep studies and explore their structural diversity, synthesis of cyathane diterpenes in a geranylgeranyl pyrophosphate engineered is investigated. Aided by homologous analyses, one new unclustered FAD-dependent oxidase EriM accounting for the formation of allyl aldehyde and three new NADP(H)-dependent reductases in the biosynthesis of cyathanes are identified and elucidated. By combinatorial biosynthetic strategy, strains generating twenty-two cyathane-type diterpenes, including seven "unnatural" cyathane xylosides (, , , , , , and ) are established. Compounds -, , and show significant neurotrophic effects on PC12 cells in the dose of 6.3-25.0 μmol/L. These studies provide new insights into the divergent biosynthesis of mushroom-originated cyathanes and a straightforward approach to produce bioactive cyathane-type diterpenes.
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http://dx.doi.org/10.1016/j.apsb.2021.04.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8463280PMC
September 2021

Comparative and Evolutionary Analyses on the Complete Plastomes of Five Horticultural Plants.

Front Plant Sci 2021 27;12:705874. Epub 2021 Aug 27.

School of Life Sciences, Zhengzhou University, Zhengzhou, China.

Many species of the genus are important horticultural plants. They have evolved the Crassulacean acid metabolism (CAM) photosynthetic pathway to allow them to be better adapted to dry environments. Despite their importance, it is still debating whether is monophyletic, and understanding the past diversification of this genus requires a tremendous amount of effort and work being devoted to the studies of morphological and molecular characters of this genus. However, molecular information, plastic sequence data, in particular, reported on species is scarce, and this has posed a great challenge in trying to interpret the evolutionary history of this genus. In this study, plastomes of the five species, including , and , were sequenced and analyzed. The results indicate that the five plastomes are comparable in size, guanine-cytosine (GC) contents and the number of genes, which also demonstrate an insignificant difference in comparison with other species from the family Crassulaceae. About 224 simple sequence repeats (SSRs) and 144 long repeats were identified in the five plastomes, and most of these are distributed in the inverted repeat regions. In addition, highly divergent regions containing either single nucleotide polymorphism (SNP) or insertion or deletion (InDel) mutations are discovered, which could be potentially used for establishing phylogenetic relationships among members of the genus in future studies. Furthermore, phylogenetic analyses suggest that should be placed into one single genus as . Further genomic analyses also reveal that several genes are undergone positive selection. Among them, 11 genes are involved in important cellular processes, such as cell survival, electron transfer, and may have played indispensable roles in the adaptive evolution of to dry environments.
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http://dx.doi.org/10.3389/fpls.2021.705874DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429837PMC
August 2021

Transmission dynamics and the effects of non-pharmaceutical interventions in the COVID-19 outbreak resurged in Beijing, China: a descriptive and modelling study.

BMJ Open 2021 09 7;11(9):e047227. Epub 2021 Sep 7.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China

Objective: To evaluate epidemiological characteristics and transmission dynamics of COVID-19 outbreak resurged in Beijing and to assess the effects of three non-pharmaceutical interventions.

Design: Descriptive and modelling study based on surveillance data of COVID-19 in Beijing.

Setting: Outbreak in Beijing.

Participants: The database included 335 confirmed cases of COVID-19.

Methods: To conduct spatiotemporal analyses of the outbreak, we collected individual records on laboratory-confirmed cases of COVID-19 from 11 June 2020 to 5 July 2020 in Beijing, and visitor flow and products transportation data of Xinfadi Wholesale Market. We also built a modified susceptible-exposed-infected-removed model to investigate the effect of interventions deployed in Beijing.

Results: We found that the staff working in the market (52.2%) and the people around 10 km to this epicentre (72.5%) were most affected, and the population mobility entering-exiting Xinfadi Wholesale Market significantly contributed to the spread of COVID-19 (p=0.021), but goods flow of the market had little impact on the virus spread (p=0.184). The prompt identification of Xinfadi Wholesale Market as the infection source could have avoided a total of 25 708 (95% CI 13 657 to 40 625) cases if unnoticed transmission lasted for a month. Based on the model, we found that active screening on targeted population by nucleic acid testing alone had the most significant effect.

Conclusions: The non-pharmaceutical interventions deployed in Beijing, including localised lockdown, close-contact tracing and community-based testing, were proved to be effective enough to contain the outbreak. Beijing has achieved an optimal balance between epidemic containment and economic protection.
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http://dx.doi.org/10.1136/bmjopen-2020-047227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424429PMC
September 2021

Higher Serum Lysophosphatidic Acids Predict Left Ventricular Reverse Remodeling in Pediatric Dilated Cardiomyopathy.

Front Pediatr 2021 16;9:710720. Epub 2021 Aug 16.

Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

The prognosis of pediatric dilated cardiomyopathy (PDCM) is highly variable, ranging from death to cardiac function recovery. Left ventricular reverse remodeling (LVRR) represents a favorable prognosis in PDCM. Disturbance of lipid metabolism is associated with the change of cardiac function, but no studies have examined lipidomics data and LVRR. Discovery analyses were based on 540 targeted lipids in an observational, prospective China-AOCC (An Integrative-Omics Study of Cardiomyopathy Patients for Diagnosis and Prognosis in China) study. The OPLS-DA and random forest (RF) analysis were used to screen the candidate lipids. Associations of the candidate lipids were examined in Cox proportional hazards regression models. Furthermore, we developed a risk score comprising the significant lipids, with each attributed a score of 1 when the concentration was above the median. All significant findings were replicated in a validation set of the China-AOCC study. There were 59 patients in the discovery set and 24 patients in the validation set. LVRR was observed in 27 patients (32.5%). After adjusting for age, left ventricular ejection fraction (LVEF), and left ventricular end-diastolic dimension (LVEDD) z-score, lysophosphatidic acids (LysoPA) 16:0, LysoPA 18:2, LysoPA 18:1, and LysoPA 18:0 were significantly associated with LVRR in the discovery set, and hazard ratios (HRs) were 2.793 (95% CI, 1.545-5.048), 2.812 (95% CI, 1.542-5.128), 2.831 (95% CI, 1.555-5.154), and 2.782 (95% CI, 1.548-5.002), respectively. We developed a LysoPA score comprising the four LysoPA. When the LysoPA score reached 4, LVRR was more likely to be observed in both sets. The AUC increased with the addition of the LysoPA score to the LVEDD z-score (from 0.693 to 0.875 in the discovery set, from 0.708 to 0.854 in the validation set) for prediction of LVRR. Serum LysoPA can predict LVRR in PDCM patients. When the LysoPA score was combined with the LVEDD z-score, it may help in ascertaining the prognosis and monitoring effects of anti-heart failure pharmacotherapy.
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http://dx.doi.org/10.3389/fped.2021.710720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415784PMC
August 2021

Whole-transcriptome analysis of rat cavernosum and identification of circRNA-miRNA-mRNA networks to investigate nerve injury erectile dysfunction pathogenesis.

Bioengineered 2021 12;12(1):6516-6528

Department of Urology and Andrology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.

There is growing evidence that circular RNAs (circRNAs) play a vital role in many kinds of diseases, including erectile dysfunction (ED). Nevertheless, the role of circRNAs in cavernous nerve-damaging ED (CNI-ED) is unknown. Here, we aimed to discover novel circRNAs, probed their potential role in the CNI-ED, and construct a ceRNA network of circRNAs. Twelve male Sprague Dawley rats were randomly divided into 2 groups by us: bilateral cavernous nerve crush (BCNC) and control groups. Four weeks after surgery, the spongy smooth muscle tissue of the rat penis was sequenced using high-throughput full transcriptome sequencing. We analyzed the expression of circRNAs, miRNAs, and mRNAs in the two groups. Twenty circRNAs with significantly different expressions were selected for RT-qPCR. CeRNA network of circRNAs was established using Cytoscape. GO and KEGG analysis was done by R package. Sequencing showed that 4,587 circRNAs, 762 miRNAs, and 21,661 mRNAs were dysregulated in the BCNC group. The top 20 differentially expressed circRNAs were further verified via RT-qPCR. The ceRNA network contained ten circRNAs, six miRNAs, and 227 mRNAs, including 23 circRNA-miRNA pairs and 227 miRNA-mRNA pairs. GO and KEGG analysis suggested that these ten circRNAs could main regulate energy metabolism processes. A protein-protein interaction network was constructed with the mRNAs in ceRNA network, and five hub genes were identified. Our study revealed a potential link between circRNAs, miRNAs, and mRNAs in CNI-ED, suggesting that circRNAs may contribute to the occurrence of ED by regulating the cellular energy metabolism in CNI-ED.
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http://dx.doi.org/10.1080/21655979.2021.1973863DOI Listing
December 2021

Network Pharmacology-Based Strategy for Predicting Active Ingredients and Potential Targets of Franchin Polycystic Ovary Syndrome.

Evid Based Complement Alternat Med 2021 18;2021:6651307. Epub 2021 Aug 18.

Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Background: Polycystic ovary syndrome (PCOS) causes low fertility in females. () is used to clear heat and dampness, purify fire, and detoxify in traditional Chinese medicine (TCM). Although has demonstrated efficacy against PCOS in clinical practice, there are no available data regarding the bioactive components of , their targets, and molecular mechanisms underlying their effects.

Methods And Results: Network pharmacology was used to analyze the bioactive components of , their targets, and signaling pathways underlying their effects. The TCM systems pharmacology database and analysis platform (TCMSP) was used to screen 14 effective active ingredients and 218 targets of . The GeneCards, OMIM, and PharmGkb databases were used to screen 3517 disease targets for PCOS, and 102 common targets of drugs and diseases were screened using R Cytoscape that was utilized to build a drug-active ingredient-disease target interaction network, and the STRING platform was utilized to construct a common target protein-protein interaction network, including 102 nodes and 221 edges. Key targets of for the treatment of PCOS included , , , , , and . A total of 123 gene ontology (GO) terms and 129 pathways were acquired by GO and KEGG enrichment analyses. The AGEs/RAGE, TNF, IL-17, MAPK, and HIF-1 signaling pathways were closely related to PCOS and may be the core pathways involved in PCOS. Schrodinger software was used to evaluate the interaction between active components and their targets and explore binding modes. Furthermore, based on the prediction of network pharmacology study, a mouse model of PCOS was established to evaluate the curative role and underlying mechanisms of . The results showed that treatment reversed histopathological damage of the ovary and also ameliorated the mRNA and protein expression levels of the predicted hub targets (MAPK1, CXCL8, IL-6, and IL-1). These results indicated that WZYZP has a protective effect on spermatogenesis disorder, suggesting that it could be an alternative choice for male infertility therapy.

Conclusions: This preliminary study verified the basic pharmacological effects and mechanisms of , a TCM, in the treatment of PCOS. These results indicate that the therapeutic effects of on PCOS may be achieved by regulating the expression of inflammatory factors. This study provides new insights for the systematic exploration of the mechanism of traditional Chinese medicine.
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http://dx.doi.org/10.1155/2021/6651307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390140PMC
August 2021

Clinical Evaluation for Sublingual Immunotherapy With in Polysensitized Allergic Asthma Patients.

Front Med (Lausanne) 2021 5;8:645356. Epub 2021 Aug 5.

Department of Allergy Medicine, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, China.

Many studies have demonstrated the efficacy of single-allergen sublingual immunotherapy (SLIT) in polysensitized patients with allergic rhinitis (AR), but less is reported in polysensitized patients with allergic asthma (AS). Data of 133 adult patients with house dust mite (HDM)-induced AS who had been treated for 3 years were collected. These patients were divided into the control group (treated with low to moderate dose of inhaled glucocorticoids and long-acting β2 agonists, = 37) and the SLIT group (further treated with drops, = 96). The SLIT group contained three subgroups: the single-allergen group (only sensitized to HDM, = 35), the 1- to 2-allergen group (HDM combined with one to two other allergens, = 32), and the 3-or-more-allergen group (HDM combined with three or more other allergens, = 29). The total asthma symptom score (TASS), total asthma medicine score (TAMS), and asthma control test (ACT) were assessed before treatment and at yearly visits. Forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) was assessed before treatment and at the end of SLIT. TASS and ACT scores in the control group were significantly higher than that in the single-allergen group and the 1- to 2-allergen group after 1, 2, and 3 years of SLIT and significantly higher than that in the 3-or-more-allergen group after 3-year SLIT (all < 0.05). TAMS of the control group was significantly higher than that of the other three groups after 0.5, 1, 2, and 3 years of SLIT (all < 0.05). FEV1/FVC in the control group was significantly higher than baseline after 3 years of immunotherapy ( < 0.05). Patients sensitized to HDM with/without other allergens showed similar efficacy after 3 years of SLIT. However, the initial response of patients with three or more allergens was slower during immunotherapy process.
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http://dx.doi.org/10.3389/fmed.2021.645356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374619PMC
August 2021

Effect of Pyrazosulfuron-Methyl on the Photosynthetic Characteristics and Antioxidant Systems of Foxtail Millet.

Front Plant Sci 2021 5;12:696169. Epub 2021 Aug 5.

State Key Laboratory of Sustainable Dryland Agriculture (in Preparation), College of Agronomy, Shanxi Agricultural University, Shanxi, China.

Foxtail millet ( L.) plays a principal role in food security in Africa and Asia, but it is sensitive to a variety of herbicides. This study was performed to clarify whether pyrazosulfuron-methyl can be used in foxtail millet fields and the effect of pyrazosulfuron-methyl on the photosynthetic performance of foxtail millet. Two foxtail millet varieties (Jingu 21 and Zhangzagu 10) were subjected to five doses (0, 15, 30, 60, and 120 g ai ha) of pyrazosulfuron-methyl in pot and field experiments. The plant height, leaf area, stem diameter, photosynthetic pigment contents, gas exchange parameters, chlorophyll fluorescence parameters, antioxidant enzyme activities, and antioxidant contents at 7 and 15 days after pyrazosulfuron-methyl application, and the yield of foxtail millet were measured. The results suggested that pyrazosulfuron-methyl inhibited the growth of foxtail millet and reduced the photosynthetic pigment contents, photosynthetic rate, and photosynthetic system II activity. Similarly, pyrazosulfuron-methyl decreased the antioxidant enzyme activities and antioxidant contents. These results also indicated that the toxicity of pyrazosulfuron-methyl to foxtail millet was decreased gradually with the extension of time after application; however, the foxtail millet yield was still significantly reduced. Therefore, pyrazosulfuron-methyl is not recommended for application in foxtail millet fields.
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http://dx.doi.org/10.3389/fpls.2021.696169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375152PMC
August 2021

Treatment of Donor-derived Carbapenem-resistant Klebsiella pneumoniae Infection after Renal Transplantation with Tigecycline and Extended-infusion Meropenem.

Curr Med Sci 2021 Aug 17;41(4):770-776. Epub 2021 Aug 17.

Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Objective: Donor-derived carbapenem-resistant Klebsiella pneumoniae (CRKP) infection has recently emerged as a critical early complication after renal transplantation. Although CRKP is usually sensitive to tigecycline, monotherapy with this drug is often less than effective. We investigated the efficacy of a combined regimen of tigecycline with high-dose, extended-infusion meropenem in the treatment of donor-derived CRKP infection after kidney transplantation.

Methods: From Jan. 2016 to Dec. 2017, a total of 12 CRKP isolates were detected from cultures of the organ preservation solution used for soaking the donor kidneys at our institute. Probable or possible donor-derived infection (DDI) was identified in 8 transplant recipients. Clinical data were retrospectively analyzed.

Results: Klebsiella pneumoniae carbapenemase-2 (KPC-2)-producing CRKP was reported to be positive in organ preservation solution cultures at 3.5±0.9 days after transplantation, leading to surgical site (n=3), urinary tract (n=4), and/or bloodstream (n=2) infections in 8 recipients. The drug susceptibility tests showed that CRKP was sensitive to tigecycline, but resistant to meropenem. In 7 patients who received tigecycline combined with high-dose extended-infusion meropenem, DDIs were successfully cured. The length of hospital stay was 31 (18-129) days, and the serum creatinine at discharge was 105.8±16.7 µmol/L. The one remaining patient who received tigecycline combined with intravenous-drip meropenem died of septic shock. A median follow-up of 43 months (33-55) showed no recurrence of new CRKP infection in the 7 surviving recipients.

Conclusion: It was suggested that a prompt and appropriate combination therapy using tigecycline with high-dose extended-infusion meropenem is effective in treating donor-derived KPC-2-producing CRKP infection after renal transplantation.
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http://dx.doi.org/10.1007/s11596-021-2397-zDOI Listing
August 2021

Twelve-month systemic consequences of COVID-19 in patients discharged from hospital: a prospective cohort study in Wuhan, China.

Clin Infect Dis 2021 Aug 14. Epub 2021 Aug 14.

National Medical Center for Major Public Health Events, Wuhan, China.

Background: Follow-up study of Coronavirus disease 2019 (COVID-19) survivors has rarely been reported. We aimed to investigate longitudinal changes in the characteristics of COVID-19 survivors after discharge.

Methods And Findings: A total of 594 COVID-19 survivors discharged from Tongji Hospital in Wuhan from February 10 to April 30, 2020 were included and followed up until May 17, 2021. Laboratory and radiological findings, pulmonary function tests, electrocardiogram, symptoms and signs were analyzed. 257 (51.2%) patients had at least one symptom at 3 months post-discharge, which decreased to 169 (40.0%) and 138 (28.4%) at 6-month and 12-month visit respectively. During follow-up period, insomnia, chest tightness, and fatigue were the most prevalent symptoms. Most laboratory parameters returned to normal, whereas increased incidence of abnormal liver and renal function and cardiovascular injury was evidenced after discharge. Fibrous stripes (213; 42.4%), pleural thickening and adhesions (188; 37.5%) and enlarged lymph nodes (120; 23.9%) were the most common radiographical findings at 3 months post-discharge. The abnormalities of pulmonary function included obstructive, restrictive, and mixed, which were 5.5%, 4.0%, 0.9% at 6 months post, and 1.9%, 4.7%, 0.2% at 12 months. Electrocardiogram abnormalities occurred in 256 (51.0%) patients at 3 months post-discharge, including arrhythmia, ST-T change and conduction block, which increased to 258 (61.1%) cases at 6-month visit and were maintained at high frequency (242;49.8%) at 12-month visit.

Conclusions: Physiological, laboratory, radiological or electrocardiogram abnormalities, particularly those related to renal, cardiovascular, liver functions are common in patients who recovered from COVID-19 up to 12months post-discharge.
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http://dx.doi.org/10.1093/cid/ciab703DOI Listing
August 2021

Early Predictors of the Increase in Perihematomal Edema Volume After Intracerebral Hemorrhage: A Retrospective Analysis From the Risa-MIS-ICH Study.

Front Neurol 2021 27;12:700166. Epub 2021 Jul 27.

Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Perihematomal edema (PHE) is associated with poor functional outcomes after intracerebral hemorrhage (ICH). Early identification of risk factors associated with PHE growth may allow for targeted therapeutic interventions. We used data contained in the risk stratification and minimally invasive surgery in acute intracerebral hemorrhage (Risa-MIS-ICH) patients: a prospective multicenter cohort study. Patients' clinical, laboratory, and radiological data within 24 h of admission were obtained from their medical records. The absolute increase in PHE volume from baseline to day 3 was defined as iPHE volume. Poor outcome was defined as modified Rankin Scale (mRS) of 4 to 6 at 90 days. Binary logistic regression was used to assess the relationship between iPHE volume and poor outcome. The receiver operating characteristic curve was used to find the best cutoff. Linear regression was used to identify variables associated with iPHE volume (ClinicalTrials.gov Identifier: NCT03862729). One hundred ninety-seven patients were included in this study. iPHE volume was significantly associated with poor outcome [ = 0.003, odds ratio (OR) 1.049, 95% confidence interval (CI) 1.016-1.082] after adjustment for hematoma volume. The best cutoff point of iPHE volume was 7.98 mL with a specificity of 71.4% and a sensitivity of 47.5%. Diabetes mellitus ( = 0.043, β = 7.66 95% CI 0.26-15.07), black hole sign ( = 0.002, β = 18.93 95% CI 6.84-31.02), and initial ICH volume ( = 0.018, β = 0.20 95% CI 0.03-0.37) were significantly associated with iPHE volume. After adjusting for hematoma expansion, the black hole sign could still independently predict the increase of PHE ( < 0.001, β = 21.62 95% CI 10.10-33.15). An increase of PHE volume >7.98 mL from baseline to day 3 may lead to poor outcome. Patients with diabetes mellitus, black hole sign, and large initial hematoma volume result in more PHE growth, which should garner attention in the treatment.
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http://dx.doi.org/10.3389/fneur.2021.700166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353085PMC
July 2021

Inhibition of Rev-erbα ameliorates muscular dystrophy.

Exp Cell Res 2021 Sep 6;406(2):112766. Epub 2021 Aug 6.

Department of Diabetes Complications & Metabolism, Beckman Research Institute of City of Hope, Duarte, CA, 91010, USA. Electronic address:

Duchene muscular dystrophy leads to progressive muscle structural and functional decline due to chronic degenerative-regenerative cycles. Enhancing the regenerative capacity of dystrophic muscle provides potential therapeutic options. We previously demonstrated that the circadian clock repressor Rev-erbα inhibited myogenesis and Rev-erbα ablation enhanced muscle regeneration. Here we show that Rev-erbα deficiency in the dystrophin-deficient mdx mice promotes regenerative myogenic response to ameliorate muscle damage. Loss of Rev-erbα in mdx mice improved dystrophic pathology and muscle wasting. Rev-erbα-deficient dystrophic muscle exhibit augmented myogenic response, enhanced neo-myofiber formation and attenuated inflammatory response. In mdx myoblasts devoid of Rev-erbα, myogenic differentiation was augmented together with up-regulation of Wnt signaling and proliferative pathways, suggesting that loss of Rev-erbα inhibition of these processes contributed to the improvement in regenerative myogenesis. Collectively, our findings revealed that the loss of Rev-erbα function protects dystrophic muscle from injury by promoting myogenic repair, and inhibition of its activity may have therapeutic utilities for muscular dystrophy.
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http://dx.doi.org/10.1016/j.yexcr.2021.112766DOI Listing
September 2021

MicroRNA-27b-3p downregulates FGF1 and aggravates pathological cardiac remodelling.

Cardiovasc Res 2021 Aug 6. Epub 2021 Aug 6.

Beijing Anzhen Hospital, Capital Medical University; The Key Laboratory of Remodelling-Related Cardiovascular Diseases, Ministry of Education; Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, 100029, China.

Aims: The heart undergoes pathological remodelling under increased stress and neuronal imbalance. MicroRNAs (miRNAs) are involved in post-transcriptional regulation of genes in cardiac physiology and pathology. However, the mechanisms underlying miRNA-mediated regulation of pathological cardiac remodelling remain to be studied. This study aimed to explore the function of endogenous microRNA-27b-3p (miR-27b-3p) in pathological cardiac remodelling.

Methods And Results: miR-27b-3p expression was elevated in the heart of a transverse aortic constriction (TAC)-induced cardiac hypertrophy mouse model. MiR-27b-knockout mice showed significantly attenuated cardiac hypertrophy, fibrosis, and inflammation induced by two independent pathological cardiac hypertrophy models, TAC and Angiotensin II (Ang II) perfusion. Transcriptome sequencing analysis revealed that miR-27b deletion significantly downregulated TAC-induced cardiac hypertrophy, fibrosis, and inflammatory genes. We identified fibroblast growth factor 1 (FGF1) as a miR-27b-3p target gene in the heart and was upregulated in miR-27b-null mice. We found that both recombinant FGF1 (rFGF1) and inhibition of miR-27b-3p enhanced mitochondrial oxidative phosphorylation (OXPHOS) and inhibited cardiomyocyte hypertrophy. Importantly, rFGF1 administration inhibited cardiac hypertrophy and fibrosis in TAC or Ang II-induced models, and enhanced OXPHOS by activating PGC1α/β.

Conclusions: Our study demonstrated that miR-27b-3p induces pathological cardiac remodelling and suggests that inhibition of endogenous miR-27b-3p or administration of FGF1 might have the potential to suppress cardiac remodelling in a clinical setting.

Translational Perspective: MicroRNAs (miRNAs) are involved in post-transcriptional regulation of genes in cardiac physiology and pathology. However, the mechanisms underlying miRNA-mediated regulation of pathological cardiac remodelling remain to be studied. We show for the first time that miR-27b deletion attenuates cardiac hypertrophy, fibrosis, and inflammation and that rFGF1 administration inhibits cardiac hypertrophy and fibrosis in TAC- or Ang II-induced models, and enhances OXPHOS by activating PGC1α/β. Our findings suggest that miR-27b-3p and FGF1 may be potential therapeutic targets to treat conditions characterised by pathological cardiac remodelling.
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http://dx.doi.org/10.1093/cvr/cvab248DOI Listing
August 2021

RSPH14 regulates the proliferation, cell cycle progression, and apoptosis of non-small cell lung cancer cells.

FEBS Open Bio 2021 Oct 25;11(10):2715-2726. Epub 2021 Aug 25.

Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center of Cancer, Tianjin, China.

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, and it is characterized by a high incidence. It is important to understand the molecular mechanisms that determine the progression and metastasis of NSCLC in order to develop more effective therapies and identify novel diagnostic indicators of NSCLC. RSPH14 has been reported to be related to multiple human diseases, including duodenal adenocarcinoma and meningiomas, but the role of RSPH14 in NSCLC remains unclear. The present study aimed to investigate the molecular function and clinical significance of RSPH14 in NSCLC. Analyses of public datasets and clinical samples demonstrated that RSPH14 expression was upregulated in NSCLC samples compared with normal samples. In addition, high RSPH14 expression was associated with a shorter overall survival time in patients with NSCLC. Notably, RSPH14 knockdown suppressed the proliferation and cell cycle progression and enhanced the apoptosis of NSCLC cells. Mechanically, tandem mass tag analysis demonstrated that RSPH14 can affect multiple processes, including the AMPK signaling pathway, calcium ion import regulation, glucose transmembrane transporter activity, and glucose transmembrane transport. Taken together, the results of the present study suggest that RSPH14 may be a promising prognostic factor and therapeutic target for NSCLC.
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http://dx.doi.org/10.1002/2211-5463.13266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487038PMC
October 2021

Two-branch 3D convolutional neural network for motor imagery EEG decoding.

J Neural Eng 2021 08 13;18(4). Epub 2021 Aug 13.

Shien-Ming Wu School of Intelligent Engineering, South China University of Technology, Guangzhou, People's Republic of China.

The original motor imagery electroencephalography (MI-EEG) data contains not only temporal features but also a large number of spatial features related to the distribution of electrodes on the brain. However, in the process of MI-EEG decoding, most of the current convolutional neural network (CNN) based methods do not make the utmost of the spatial features related to electrode distribution.In this study, we adopt a concise 3D representation for the MI-EEG data to take full advantage of the spatial features and propose a two-branch 3D CNN (TB-3D CNN) for the 3D representation of MI-EEG data. First, the spatial and temporal features of the input 3D samples are extracted by the spatial and temporal feature learning branches, respectively, to avoid the mutual interference between the temporal and spatial features. Then, the central loss is introduced into the TB-3D CNN framework to further improve the MI-EEG decoding accuracy. And a 3D data augmentation method based on the cyclic translation of time dimension is proposed for the 3D representation method to alleviate the overfitting problem.Some experiments are conducted on the famous BCI competition IV 2a dataset to evaluate the effectiveness of the proposed MI-EEG decoding method. The experimental results comparison with some state-of-the-art methods demonstrates that the average accuracy of our method is 4.42% higher than that of the best of the comparative methods.The proposed MI-EEG decoding method has great promise to improve the performance of motor imagery brain-computer interface system.
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http://dx.doi.org/10.1088/1741-2552/ac17d6DOI Listing
August 2021

A novel multiple subdivision-based algorithm for quantitative assessment of retinal vascular tortuosity.

Exp Biol Med (Maywood) 2021 Jul 25:15353702211032898. Epub 2021 Jul 25.

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

Vascular tortuosity as an indicator of retinal vascular morphological changes can be quantitatively analyzed and used as a biomarker for the early diagnosis of relevant disease such as diabetes. While various methods have been proposed to evaluate retinal vascular tortuosity, the main obstacle limiting their clinical application is the poor consistency compared with the experts' evaluation. In this research, we proposed to apply a multiple subdivision-based algorithm for the vessel segment vascular tortuosity analysis combining with a learning curve function of vessel curvature inflection point number, emphasizing the human assessment nature focusing not only global but also on local vascular features. Our algorithm achieved high correlation coefficients of 0.931 for arteries and 0.925 for veins compared with clinical grading of extracted retinal vessels. For the prognostic performance against experts' prediction in retinal fundus images from diabetic patients, the area under the receiver operating characteristic curve reached 0.968, indicating a good consistency with experts' predication in full retinal vascular network evaluation.
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http://dx.doi.org/10.1177/15353702211032898DOI Listing
July 2021

Multifunctional Conjugated Ligand Engineering for Stable and Efficient Perovskite Solar Cells.

Adv Mater 2021 Aug 5;33(32):e2100791. Epub 2021 Jul 5.

Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, 47907, USA.

Surface passivation is an effective way to boost the efficiency and stability of perovskite solar cells (PSCs). However, a key challenge faced by most of the passivation strategies is reducing the interface charge recombination without imposing energy barriers to charge extraction. Here, a novel multifunctional semiconducting organic ammonium cationic interface modifier inserted between the light-harvesting perovskite film and the hole-transporting layer is reported. It is shown that the conjugated cations can directly extract holes from perovskite efficiently, and simultaneously reduce interface non-radiative recombination. Together with improved energy level alignment and the stabilized interface in the device, a triple-cation mixed-halide medium-bandgap PSC with an excellent power conversion efficiency of 22.06% (improved from 19.94%) and suppressed ion migration and halide phase segregation, which lead to a long-term operational stability, is demonstrated. This strategy provides a new practical method of interface engineering in PSCs toward improved efficiency and stability.
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http://dx.doi.org/10.1002/adma.202100791DOI Listing
August 2021

Therapeutic Effect of Electronic Endoscopic Hematoma Removal on Hypertensive Basal Ganglia Cerebral Hemorrhage Based on Smart Medical Technology.

J Healthc Eng 2021 8;2021:7486249. Epub 2021 Jun 8.

Graduate School of Hebei North University, Handan 056008, Hebei, China.

The medical and health industry has successively experienced three stages of digital medical treatment, local area network medical treatment, and internet medical treatment. With the rapid development of technologies such as the Internet of Things, big data, and artificial intelligence, emerging applications and service models have gradually penetrated into all aspects of the medical and health field. At this point, the informatization development process of the medical industry has entered the stage of smart medical treatment. (Smart medical system is a new medical system that improves users' medical experience and provides users with better services. Due to the cumbersome, complicated, and mechanically rigid environment of the past medical service, there was no uniform standard. In order to create a reliable and open medical service environment, an intelligent medical system came into being.). A diversified technical foundation and smart medical protection, conducive to providing patients with high-quality medical services, are established. This article mainly introduces the analysis of the therapeutic effect of smart medical electronic endoscopic hematoma removal on hypertensive basal ganglia cerebral hemorrhage and aims to inject advanced technology and vitality of smart medical treatment into the treatment of hypertensive basal ganglia cerebral hemorrhage by hematoma removal and help the doctor to treat the patient. This article proposes the research methods of smart medical application in the treatment of hypertensive basal ganglia cerebral hemorrhage with electronic endoscopic hematoma removal, including smart medical overview, intracranial hematoma removal for hypertensive basal ganglia cerebral hemorrhage, and smart medical bioelectric signal classification. The recognition algorithm is used to realize the smart medical application of the electronic endoscopic hematoma removal in the treatment of hypertensive cerebral hemorrhage in the basal ganglia area. The experimental results show that the removal of intracranial hematoma based on smart medicine can effectively improve the removal rate of intracranial hematoma, with a recovery rate of 26.73% and a significant efficiency of 36.49%.
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http://dx.doi.org/10.1155/2021/7486249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208846PMC
June 2021

Honokiol inhibits proliferation of colorectal cancer cells by targeting anoctamin 1/TMEM16A Ca -activated Cl channels.

Br J Pharmacol 2021 Oct 16;178(20):4137-4154. Epub 2021 Aug 16.

Department of Ion Channel Pharmacology, School of Pharmacy, China Medical University, Shenyang, China.

Background And Purpose: Ca -activated Cl channels (Ano1 channels) contribute to the pathogenesis of colorectal cancer. Honokiol is known to inhibit cell proliferation and tumour growth in colorectal cancer. However, the molecular target of honokiol remains unclear. This study aimed to investigate whether honokiol inhibited cell proliferation of colorectal cancer by targeting Ano1 channels.

Experimental Approach: Patch-clamp techniques were performed to study the effect of honokiol on Ca -activated Cl currents in HEK293 cells overexpressing Ano1- or Ano2-containing plasmids or in human colorectal carcinoma SW620 cells. Site-directed mutagenesis was used to identify the critical residues for honokiol-induced Ano1 inhibition. Proliferation of SW620 cells or human intestinal epithelial NCM460 cells by CCK-8 assays.

Key Results: Honokiol blocked Ano1 currents in Ano1-overexpressing HEK293 cells and SW620 cells. Honokiol more potently inhibited Ano1 currents than Ano2 currents. Three amino acids (R429, K430 and N435) were critical for honokiol-induced Ano1 inhibition. The R429A/K430L/N435G mutation reduced the sensitivity of Ano1 to honokiol. Honokiol inhibited SW620 cell proliferation, and this effect was reduced by Ano1-shRNAs. Furthermore, Ano1 overexpression promoted proliferation in NCM460 cells with low Ano1 endogenous expression and resulted in an increased sensitivity to honokiol. Overexpression of the R429A/K430L/N435G mutation reduced WT Ano1-induced increase in the sensitivity of NCM460 cells to honokiol.

Conclusion And Implications: We identified a new anticancer mechanism of honokiol, through the inhibition of cell proliferation, by targeting Ano1 Ca -activated Cl channels.
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http://dx.doi.org/10.1111/bph.15606DOI Listing
October 2021

A New Model of Heart Failure Post-Myocardial Infarction in the Rat.

J Vis Exp 2021 06 10(172). Epub 2021 Jun 10.

College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine; Shandong Co-Innovation Center of Classic TCM Formula, Shandong Provincial Education Department;

Ligation of the left anterior descending (LAD) coronary artery has been widely used to establish the rat model of heart failure (HF) post myocardial infarction (MI). However, the disadvantages of this model include high mortality rate after ligation and larger variations both in the infarct size and the degree of impaired cardiac function. In addition, a ventilator or exteriorization of the heart is indispensable for the previous models, which complicates the procedure during the ligation. In this study, we developed a reliable and reproducible model without the ventilator or exteriorization of the heart by ligating the LAD coronary artery. Four weeks after the procedure, we found that the serum concentrations of CK-MB, NT-proBNP, and Renin, which were used to assist diagnoses of MI and HF, were significantly higher in the MI group compared to the sham group. In contrast, the value of left ventricle ejection fraction (LVEF) in the MI group was obviously less than in the sham group. Furthermore, the infarct size and cardiac fibrosis area were individually confirmed and quantitatively analyzed by TTC staining and Masson's trichrome staining. Smaller variations were found in either infarct size or fibrosis area in the MI group, which helped to develop a reliable and reproducible model of HF post-MI. This new model of HF post-MI in the rat is vital for studying the potential mechanisms of MI and HF. This new method can be used to develop the new drug for treatment of MI and HF in rats by using pharmacological strategies.
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http://dx.doi.org/10.3791/62540DOI Listing
June 2021

Efficacy and safety of pulsed radiofrequency modulation of thoracic dorsal root ganglion or intercostal nerve on postherpetic neuralgia in aged patients: a retrospective study.

BMC Neurol 2021 Jun 24;21(1):233. Epub 2021 Jun 24.

Department of Pain, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, PR China.

Background: Postherpetic neuralgia (PHN) is common in elderly patients and can be alleviated by pulsed radiofrequency (PRF). However, PRF treatments display different efficacy on different nerves. The purpose of this study was to evaluate the efficacy and safety of ultrasound-guided PRF modulation on thoracic dorsal root ganglion (DRG) or intercostal nerve (ICN) for PHN in aged patients and to provide a theoretical basis for clinical treatment.

Methods: We classified aged patients into two groups, DRG group and ICN group, based on the needle tip position. Visual analogue scale (VAS) and concise health status questionnaire (Short-form 36 health/survey questionnaire, SF-36) were used to evaluate the pain intensity and the life quality of the patients before and 2, 4 and 12 weeks after the PRF treatments. We also recorded the adverse reactions during the treatments.

Results: After the PRF treatment, the scores of VAS and SF-36 (assessing general health perception, social function, emotional role, mental health, and pain) improved significantly in both groups (P < 0.05). The mean VAS score in the DRG group was significantly lower than that in the ICN group 2 weeks after treatment, and remained for 12 weeks. The SF-36 scores in the DRG group were significantly higher than those in the ICN group (P < 0.05). We found a similar incidence of adverse reactions between the two groups (P > 0.05).

Conclusions: PRF therapy is safe and effective for elderly patients with postherpetic neuralgia. However, PRF treatment in dorsal root ganglion is superior to that in intercostal nerve with improving VAS and SF-36 scores to a greater extent in older patients.

Trial Registration: ChiCTR2100044176 .
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http://dx.doi.org/10.1186/s12883-021-02286-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8223296PMC
June 2021

The role of circTMOD3 in regulating LPS-induced acute inflammation and injury in human lung fibroblast WI-38 cells.

Exp Lung Res 2021 Sep 20;47(7):311-322. Epub 2021 Jun 20.

Department of Pediatrics, Affiliated Hospital of Yan'an University, Yan'an, China.

Background: Circular RNAs (circRNAs) have been implicated in the molecular etiology of pediatric pneumonia. Here, we investigated the precise action of circRNA tropomodulin 3 (circTMOD3, hsa_circ_0035292) in cell injury and inflammation induced by lipopolysaccharide (LPS). Cell viability was gauged by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis and cycle distribution were assessed by flow cytometry. Enzyme-linked immunosorbent assay (ELISA) was used to measure interleukin-6 (IL-6), IL-1β and tumor necrosis factor alpha (TNF-α) production. The levels of circTMOD3, microRNA (miR)-146b-3p, and C-X-C motif chemokine receptor 1 (CXCR1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Ribonuclease (RNase) R, Actinomycin D and subcellular localization assays were done to characterize circTMOD3. The direct relationship between miR-146b-3p and circTMOD3 or CXCR1 was confirmed by dual-luciferase reporter assays. Our data showed that LPS induced the expression of circTMOD3 in WI-38 cells. CircTMOD3 was resistant to RNase R and was mainly present in the cytoplasm. Silencing endogenous circTMOD3 alleviated WI-38 cell injury and inflammation triggered by LPS. Mechanistically, circTMOD3 directly targeted miR-146b-3p, and CXCR1 was a direct and functional target of miR-146b-3p. CircTMOD3 regulated LPS-induced cell inflammation and injury by targeting miR-146b-3p, and miR-146b-3p-mediated suppression of CXCR1 impacted LPS-evoked cytotoxicity and inflammation. Furthermore, circTMOD3 functioned as a competing endogenous RNA (ceRNA) for miR-146b-3p to induce CXCR1 expression. Our findings demonstrated the regulation of circTMOD3 in LPS-induced cell injury and inflammation at least partially via miR-146b-3p-independent modulation of CXCR1.
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http://dx.doi.org/10.1080/01902148.2021.1940376DOI Listing
September 2021

STING Contributes to Host Defense Against Pneumonia Through Suppressing Necroptosis.

Front Immunol 2021 31;12:636861. Epub 2021 May 31.

Key Laboratory of Zoonosis Research, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China.

STING (Stimulator of interferon genes) is known as an important adaptor protein or direct sensor in the detection of nucleotide originating from pathogens or the host. The implication of STING during pulmonary microbial infection remains unknown to date. Herein, we showed that STING protected against pulmonary infection by suppressing necroptosis. STING deficiency resulted in increased mortality, more bacteria burden in BALF and lungs, severe destruction of lung architecture, and elevated inflammatory cells infiltration and inflammatory cytokines secretion. STING deficiency also had a defect in bacterial clearance, but did not exacerbate pulmonary inflammation during the early stage of infection. Interestingly, TUNEL staining and LDH release assays showed that STING mice had increased cell death than WT mice. We further demonstrated that STING mice had decreased number of macrophages accompanied by increased dead macrophages. Our and findings further demonstrated this cell death as necroptosis. The critical role of necroptosis was detected by the fact that MLKL mice exhibited decreased macrophage death and enhanced host defense to infection. Importantly, blocking necroptosis activation rescued host defense defect against pneumonia in STING mice. Hence, these results reveal an important role of STING in suppressing necroptosis activation to facilitate early pathogen control during pulmonary infection.
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http://dx.doi.org/10.3389/fimmu.2021.636861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202078PMC
May 2021

Dapagliflozin: a sodium-glucose cotransporter 2 inhibitor, attenuates angiotensin II-induced cardiac fibrotic remodeling by regulating TGFβ1/Smad signaling.

Cardiovasc Diabetol 2021 06 11;20(1):121. Epub 2021 Jun 11.

Cardiovascular Department, The First Affiliated Hospital, Fujian Medical University, Fujian Institute of Hypertension, 20 Chazhong Road, Fuzhou, 350005, China.

Background: Cardiac remodeling is one of the major risk factors for heart failure. In patients with type 2 diabetes, sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of the first hospitalization for heart failure, possibly through glucose-independent mechanisms in part, but the underlying mechanisms remain largely unknown. This study aimed to shed light on the efficacy of dapagliflozin in reducing cardiac remodeling and potential mechanisms.

Methods: Sprague-Dawley (SD) rats, induced by chronic infusion of Angiotensin II (Ang II) at a dose of 520 ng/kg per minute for 4 weeks with ALZET® mini-osmotic pumps, were treated with either SGLT2 inhibitor dapagliflozin (DAPA) or vehicle alone. Echocardiography was performed to determine cardiac structure and function. Cardiac fibroblasts (CFs) were treated with Ang II (1 μM) with or without the indicated concentration (0.5, 1, 10 μM) of DAPA. The protein levels of collagen and TGF-β1/Smad signaling were measured along with body weight, and blood biochemical indexes.

Results: DAPA pretreatment resulted in the amelioration of left ventricular dysfunction in Ang II-infused SD rats without affecting blood glucose and blood pressure. Myocardial hypertrophy, fibrosis and increased collagen synthesis caused by Ang II infusion were significantly inhibited by DAPA pretreatment. In vitro, DAPA inhibit the Ang II-induced collagen production of CFs. Immunoblot with heart tissue homogenates from chronic Ang II-infused rats revealed that DAPA inhibited the activation of TGF-β1/Smads signaling.

Conclusion: DAPA ameliorates Ang II-induced cardiac remodeling by regulating the TGF-β1/Smad signaling in a non-glucose-lowering dependent manner.
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http://dx.doi.org/10.1186/s12933-021-01312-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196449PMC
June 2021

Poisoning Attack against Estimating from Pairwise Comparisons.

IEEE Trans Pattern Anal Mach Intell 2021 Jun 8;PP. Epub 2021 Jun 8.

As pairwise ranking becomes broadly employed for elections, sports competitions, recommendation, and so on, attackers have strong motivation and incentives to manipulate the ranking list. They could inject malicious comparisons into the training data to fool the victim. Such a technique is called '`poisoning attack'' in regression and classification tasks. In this paper, to the best of our knowledge, we initiate the first systematic investigation of data poisoning attack on pairwise ranking algorithms, which can be formalized as the dynamic and static games between the ranker and the attacker, and can be modeled as certain kinds of integer programming problems. To break the computational hurdle of the underlying integer programming problems, we reformulate them into the distributionally robust optimization (DRO) problems, which are computational tractable. Based on such DRO formulations, we propose two efficient poisoning attack algorithms and establish the associated theoretical guarantees. The effectiveness of the suggested poisoning attack strategies is demonstrated by a series of toy simulations and several real data experiments. These experimental results show that the proposed methods can significantly reduce the performance of the ranker in the sense that the correlation between the true ranking list and the aggregated results can be decreased dramatically.
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http://dx.doi.org/10.1109/TPAMI.2021.3087514DOI Listing
June 2021
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