Publications by authors named "Lei Cao"

778 Publications

The application of locking-taper implants in posterior area implant restoration with insufficient occlusal-gingival distances.

Am J Transl Res 2021 15;13(6):7221-7227. Epub 2021 Jun 15.

Department of Stomatology, Jiaozhou Central Hospital of Qingdao Qingdao, Shandong Province, China.

Objective: We aimed to investigate the effect of locking-taper implants on restoration in the posterior teeth area with insufficient occlusal-gingival distances.

Methods: Forty-five patients undergoing dental implants in our hospital with occlusal-gingival distances under 5 mm in the posterior teeth area were recruited for this retrospective study. A total of 78 locking-taper implants were implanted in these patients. The patients were followed up for two years to observe the implant retention rate, the implant bone heights at different time points after the restoration, and the effects of the different implant placement depths on the marginal bone mass at the implants. Meanwhile, we evaluated the peri-implant soft tissue status by measuring the modified plaque index, the gingival index, and probing the depths. The postoperative complications and the patient satisfaction levels were also analyzed.

Results: During the 2-year follow-up, the patients' implant retention rate was 100.00%. The implant placement depths did not affect the marginal bone masses at the implants at T0-T1 or T1-T2 (T0: the day after the restoration, T1: at one year after the restoration, T2: at two years after the restoration, all P>0.05). The peri-implant soft tissues in most of the patients were in good condition, and only a few patients had a small amount of plaque or slight gingival swelling. The average probe depth was 3.23±1.20 mm during the follow-up. Only one patient had abutment loosening, and one had a dental prosthesis fall off. The patients did not feel any numbness, continuous pain, or other abnormalities during the follow-up, and the overall patient satisfaction rate was over 97.78%.

Conclusion: Locking-taper implants can achieve good clinical outcomes in the restoration of the posterior area with insufficient occlusal-gingival distances. The implants can achieve a high implant retention rate, have no adverse effects on the peri-implant soft tissues, have a low complication rate, cause no significant marginal bone mass loss at the implants, and have a high patient satisfaction rate.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290773PMC
June 2021

[Effect of early mechanical ventilation on the expression of inflammatory factors and prognosis in patients with severe traumatic brain injury].

Zhonghua Wei Zhong Bing Ji Jiu Yi Xue 2021 Jun;33(6):727-730

Department of Critical Care Medicine, Xinhua Hospital Chongming Branch, Shanghai 202150, China.

Objective: To observe the effect of early mechanical ventilation on the expression of inflammatory factors and prognosis of patients with severe traumatic brain injury (sTBI).

Methods: From January 2017 to December 2020, 138 patients with sTBI admitted to the department of the emergency of Xinhua Hospital Chongming Branch were enrolled. Although some patients were admitted to hospital without acute respiratory failure, their Glasgow coma score (GCS) were less than 8, they bad risk of hypoxia, so early mechanical ventilation was required. According to the patient's condition and the willingness of family members, patients were divided into mechanical ventilation group (tracheal intubation mechanical ventilation) and conventional oxygen inhalation group (nasal catheter or mask oxygen inhalation) in the end. The arterial partial pressure of oxygen (PaO), arterial partial pressure of carbon dioxide (PaCO), oxygenation index (PaO/FiO), tumor necrosis factor-α (TNF-α), and interleukin (IL-6, IL-10) levels at admission, preoperation and 72 hours postoperation, as well as GCS before operation and 1 week after operation, the duration and number of patients successfully evacuated from the ventilator within 1 week after surgery were observed and analyzed.

Results: A total of 138 sTBI patients were enrolled in the study, including 72 cases in the mechanical ventilation group and 66 cases in the routine oxygen inhalation group. In the two groups, PaO, PaO/FiO and IL-10 were higher, and PaCO, TNF-α and IL-6 were lower at 72 hours post operation than that before operation. Moreover, the changes in the mechanical ventilation group were more significant than those in the conventional oxygen inhalation group [PaO (1 mmHg = 0.133 kPa): 94.6±7.7 vs. 92.5±6.8, PaO/FiO (mmHg): 351±94 vs. 319±89, IL-10 (ng/L): 8.2±2.7 vs. 7.4±1.8, PaCO (mmHg): 35.6±1.8 vs. 37.5±2.7, TNF-α(ng/L): 71.5±6.3 vs. 96.8±15.5, IL-6 (ng/L): 10.8±3.9 vs. 14.4±6.5, all P < 0.05]. There were 17 patients with severe respiratory insufficiency or failure in the conventional oxygen inhalation group before operation. Compared with the conventional oxygen inhalation group, the GCS score (11.7±3.1 vs. 9.1±4.6) and the proportion of successful weaning [62.5% (45/72) vs. 44.0% (29/66)] were significantly higher, and the duration of successful weaning (hours: 63.5±28.6 vs. 88.1±33.9) was significantly shorter in the mechanical ventilation group 1 week after operation.

Conclusions: Early mechanical ventilation in sTBI patients can significantly improve oxygen supply, inhibit the release of pro-inflammatory factors, reduce secondary brain damage, and effectively improve the prognosis.
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http://dx.doi.org/10.3760/cma.j.cn121430-20210111-00046DOI Listing
June 2021

MG53 suppresses NFκB activation to mitigate age-related heart failure.

JCI Insight 2021 Jul 22. Epub 2021 Jul 22.

Department of Surgery, The Ohio State University, Columbus, United States of America.

Aging is associated with chronic oxidative stress and inflammation that impact the tissue repair and regeneration capacity. MG53 is a TRIM family protein that facilitates repair of cell membrane injury in a redox-dependent manner. Here we demonstrate that the expression of MG53 is reduced in failing human heart and aging mouse heart, concomitant with elevated NFκB activation. We evaluate the safety and efficacy of longitudinal, systemic administration of recombinant human MG53 (rhMG53) protein in aged mice. Echocardiography and pressure-volume loop measurements reveal beneficial effects of rhMG53 treatment in improving heart function of aging mice. Biochemical and histological studies demonstrate the cardioprotective effects of rhMG53 are linked to suppression of NFκB-mediated inflammation, reducing apoptotic cell death and oxidative stress in the aged heart. Repetitive administrations of rhMG53 in aged mice do not have adverse effects on major vital organ functions. These findings support the therapeutic value of rhMG53 in treating age-related decline in cardiac function.
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http://dx.doi.org/10.1172/jci.insight.148375DOI Listing
July 2021

Lower tibial shaft spiral fracture concurrent with distal tibial triplane fracture.

Curr Med Imaging 2021 Jul 16. Epub 2021 Jul 16.

Department of Radiology, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, Hebei Province, China.

Background: The clinical and imaging features of lower tibial shaft spiral fracture, concurrent with distal tibial triplane fracture, are not clear.

Introduction: Consequently, this study was aimed to investigate these features for correct diagnosis, treatment, and prevention of possible premature physeal arrest or angular deformation.

Method: Patients with lower tibial shaft spiral fracture concurrent with distal tibial triplane fracture were enrolled, and the clinical, imaging, treatment, and follow-up data were analyzed.

Result: Five patients with lower tibial shaft spiral fracture concurrent with distal tibial triplane fracture were found, including four men and one woman with an age range of 12-15 years (mean 13.6). Injury to the distal tibial epiphysis was missed in the diagnosis in plain radiography reports, but careful reevaluation confirmed distal tibial epiphysis fracture in four cases, including Salter-Harris type II in three cases and type III in one case. The remaining case had no apparent distal tibial epiphysis injury in the plain radiograph. CT scan revealed that all five patients had distal tibial triplane fracture of the lateral type, including two fragments in three cases and three fragments in two cases. The fracture was divided into type I(within the articular weight-bearing line) in three cases, type II (outside the articular weight-bearing line) in two cases that were based on the involvement of the articular surface by the fracture line. For the lower tibial fracture, one patient was treated with closed reduction and fixation with an elastic nail, three patients had internal plate fixation, and the remaining patient had cast immobilization. Having followed up for 3-11 months (mean 7), all the distal tibial fractures and the triplane fractures were healed without varus or valgus deformity in the ankle.

Conclusion: Distal tibial triplane fracture can be readily missed in plain radiography and should be suspected in patients with distal tibial spiral fracture, which should be evaluated with a computed tomographic scan.
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http://dx.doi.org/10.2174/1573405617666210716170213DOI Listing
July 2021

Optimized response of the AlGaN/GaN heterostructure with asymmetric gratings at oblique incidence in the terahertz regime.

J Opt Soc Am A Opt Image Sci Vis 2021 Jul;38(7):933-939

The performance of terahertz (THz) detectors based on two-dimensional electron gas (2DEG) with the aid of a subwavelength gratings coupler depends critically on the amplitude difference of an electric field with positive and negative scattering orders. An efficient method was proposed to enhance the current response of the AlGaN/GaN material in the frequency range from 0 to 5 THz under oblique incidence of THz radiation with asymmetric gratings, where the optimal incidence angle exists. The case of symmetric gratings was also studied for comparison. The results will be useful for the theoretical and experimental optimization of grating-assisted THz detectors without electrical bias.
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http://dx.doi.org/10.1364/JOSAA.425358DOI Listing
July 2021

Iron and nitrogen-co-doped carbon quantum dots for the sensitive and selective detection of hematin and ferric ions and cell imaging.

Analyst 2021 Jul;146(15):4954-4963

CAS Key Laboratory of Biomedical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science (CAS), Suzhou 215163, P. R. China.

Iron, nitrogen-co-doped carbon quantum dots (Fe,N-CDs) were prepared via a simple one-step hydrothermal method. The quantum yield of fluorescence reached about 27.6% and the blue-emissive Fe,N-CDs had a mean size of 3.76 nm. The as-prepared carbon quantum dots showed good solubility, a high quantum yield, good biocompatibility, low cytotoxicity, and high photostability. Interestingly, the as-prepared Fe,N-CDs exhibited good selectivity and sensitivity toward both hematin and ferric ions, and the limit of detection for hematin and ferric ions was calculated to be about 0.024 μM and 0.64 μM, respectively. At the same time, Fe,N-CDs were used for imaging HeLa cells and showed that most Fe,N-CDs were detained in the lysosome. Thus, this fluorescent probe has potential application in the quantitative detection of hematin or Fe3+ in a complex environment and for determining Fe3+ at the cellular level.
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http://dx.doi.org/10.1039/d1an00828eDOI Listing
July 2021

HP0487 contributes to the virulence of Streptococcus suis serotype 2 by mediating bacterial adhesion and anti-phagocytosis to neutrophils.

Vet Microbiol 2021 Jun 23;260:109164. Epub 2021 Jun 23.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, 430070, China; Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, 430070, China; Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Wuhan, 430070, China. Electronic address:

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that poses a serious threat to human health and the swine industry. The survival and travel in the bloodstream are the important causes for SS2, contributing to bacteremia, septicemia even septic shock. However, the related mechanism remains largely unknown. Preliminary experiment demonstrated that SS2 could largely attach to the surface of neutrophils, implying that this phenomenon maybe contributed to the travel of SS2 in bloodstream and then influenced its pathogenicity. To confirm this hypothesis, using a previously established screening method that combines affinity chromatography (based on liquid chromatography-tandem mass spectrometry) with shotgun proteomics, three candidate proteins (HP0487, HP1765, and HP1111) were identified from SS2 that could interact with neutrophils. Next, by constructing the deletion mutations, we demonstrated that HP0487 of three proteins could significantly influence the adhesion of SS2 to neutrophils. Furthermore, HP0487 was shown to contribute to the anti-phagocytosis of SS2 to neutrophils and RAW264.7 cells. More importantly, the deletion of HP0487 significantly reduced lethality and bacterial loads in vivo of SS2. Thus, our findings demonstrate that HP0487 contributes to SS2 virulence by mediating the adhesion and anti-phagocytosis of SS2 to neutrophils, promoting a better understanding about the pathogenesis of SS2.
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http://dx.doi.org/10.1016/j.vetmic.2021.109164DOI Listing
June 2021

Cyan-emitting silicon quantum dots as a fluorescent probe directly used for highly sensitive and selective detection of chlorogenic acid.

Talanta 2021 Oct 29;233:122465. Epub 2021 Apr 29.

CAS Key Laboratory of Biomedical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Science (CAS), Suzhou, 215163, China. Electronic address:

As an important bioactive component in plants, chlorogenic acid (CGA) has been widely studied for its potential role in human health. In this work, cyan fluorescent silicon quantum dots were successfully synthesized via a simple one-pot method for the rapid detection of CGA. The optimal excitation and emission wavelength of the obtained SiQDs was 350 nm and 470 nm, respectively. When the CGA was added, the maximum emission intensity of the SiQDs can be effectively quenched due to dynamic and static mixed quenching mechanisms. More significantly, there was a remarkable linear correlation between fluorescence quenching efficiency and a broad concentration of CGA solution range from 10 to 150 μmol/L with a limit of detection (LOD) of 0.43 μmol/L. Furthermore, the proposed SiQDs were successfully applied to analyze CGA in coffee beans and instant coffee after simple pretreatment with satisfactory results. Based on these, a high sensitivity and excellent selectivity fluorescent probe detection system was constructed, and it provides a valuable platform for the detection of CGA and has broad application prospects in the biological and pharmaceutical analysis field.
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http://dx.doi.org/10.1016/j.talanta.2021.122465DOI Listing
October 2021

Bionic Birdlike Imaging Using a Multi-Hyperuniform LED Array.

Sensors (Basel) 2021 Jun 14;21(12). Epub 2021 Jun 14.

School of Instrumentation and Optoelectronic Engineering, Beihang University, Beijing 100191, China.

Digital cameras obtain color information of the scene using a chromatic filter, usually a Bayer filter, overlaid on a pixelated detector. However, the periodic arrangement of both the filter array and the detector array introduces frequency aliasing in sampling and color misregistration during demosaicking process which causes degradation of image quality. Inspired by the biological structure of the avian retinas, we developed a chromatic LED array which has a geometric arrangement of multi-hyperuniformity, which exhibits an irregularity on small-length scales but a quasi-uniformity on large scales, to suppress frequency aliasing and color misregistration in full color image retrieval. Experiments were performed with a single-pixel imaging system using the multi-hyperuniform chromatic LED array to provide structured illumination, and 208 fps frame rate was achieved at 32 × 32 pixel resolution. By comparing the experimental results with the images captured with a conventional digital camera, it has been demonstrated that the proposed imaging system forms images with less chromatic moiré patterns and color misregistration artifacts. The concept proposed verified here could provide insights for the design and the manufacturing of future bionic imaging sensors.
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http://dx.doi.org/10.3390/s21124084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231846PMC
June 2021

Combined strategies for effective cancer immunotherapy with a novel anti-CD47 monoclonal antibody.

Cancer Immunol Immunother 2021 Jun 24. Epub 2021 Jun 24.

Innovent Biologics (Suzhou) Co., Ltd, 168 Dongping Street, Suzhou Industrial Park, Suzhou, 215123, Jiangsu, China.

CD47 is a widely expressed cell-surface protein that regulates phagocytosis mediated by cells of the innate immune system, such as macrophages and dendritic cells. CD47 serves as the ligand for a receptor on these innate immune cells, signal regulatory protein (SIRP)-α, which in turn inhibits phagocytosis. Several targeted CD47 therapeutic antibodies have been investigated clinically; however, how to improve its therapeutic efficacy remains unclear. Herein, we developed a CD47 blocking antibody, named IBI188, that could specifically block the CD47-SIRP-α axis, which transduces the "don't eat me" signal to macrophages. In vitro phagocytosis assays demonstrated the pro-phagocytosis ability of IBI188. Furthermore, several in vivo models were chosen to evaluate the anti-tumor efficacy of IBI188. IBI188 treatment upregulated cell movement- and inflammation-related genes in macrophages. Synergism was observed when combined with an anti-CD20 therapeutic antibody, whose function depends on antibody-dependent cellular cytotoxicity/phagocytosis (ADCC/ADCP). CD47 expression was evaluated following azacytidine (AZA) treatment, a standard-of-care for patients with multiple myeloma; enhanced anti-tumor efficacy was observed in the combination group in AML xenograft models. Notably, IBI188 treatment increased vascular endothelial growth factor-A (VEGF-A) levels in a solid tumor model, and combined treatment with an anti-VEGF-A antibody and IBI188 resulted in an enhanced anti-tumor effect. These data indicate that IBI188 is a therapeutic anti-CD47 antibody with anti-tumor potency, which can be enhanced when used in combination with standard-of-care drugs for cancer treatment.
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http://dx.doi.org/10.1007/s00262-021-02989-2DOI Listing
June 2021

Category-Aware Chronic Stress Detection on Microblogs.

IEEE J Biomed Health Inform 2021 Jun 18;PP. Epub 2021 Jun 18.

People today live a stressful life. Compared with acute stress, long-term chronic stress is more harmful, and may cause or exacerbate many serious health problems, including high blood pressure, heart disease, chronic pain, and mental diseases. With social media becoming an integral part of our daily lives for information sharing and self-expression, detecting category-aware long-standing chronic stress from a large volume of historic open posts made by social media users is possible. In this study, we construct a data set containing 971 chronically stressed users with totally 54,546 open posts on Sina microblog from July 5, 2018 to December 1, 2019, and design two techniques for category-aware chronic stress detection: (1) a stress-oriented word embedding on the basis of an existing pre-trained word embedding, aiming to strengthen the sensibility of stress-related expressions for linguistic post analysis; (2) a multi-attention model with three layers (i.e., category-attention layer, posts self-attention layer, and category-specific post attention layer), aiming to capture inter-relevance from a sequence of posts and infer long-term stress categories and stress levels. The experimental results show that the proposed multi-attention model equipped with the stress-oriented word embedding can achieve (accuracy 80.65%, recall 80.92%, precision 80.48%, and F1-measure 80.70%) in detecting category-aware stress levels, (accuracy 86.49%, recall 86.79%, precision 86.68%, and F1-measure 86.71%) in detecting chronic stress levels only, and (accuracy 93.07%, recall 92.56%, precision 93.15%, and F1-measure 92.85%) in detecting chronic stress categories only. Limitations and implications of the study are also discussed at the end of the paper.
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http://dx.doi.org/10.1109/JBHI.2021.3090467DOI Listing
June 2021

Ultrasensitive detection of circulating tumour DNA via deep methylation sequencing aided by machine learning.

Nat Biomed Eng 2021 Jun 15;5(6):586-599. Epub 2021 Jun 15.

Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai, China.

The low abundance of circulating tumour DNA (ctDNA) in plasma samples makes the analysis of ctDNA biomarkers for the detection or monitoring of early-stage cancers challenging. Here we show that deep methylation sequencing aided by a machine-learning classifier of methylation patterns enables the detection of tumour-derived signals at dilution factors as low as 1 in 10,000. For a total of 308 patients with surgery-resectable lung cancer and 261 age- and sex-matched non-cancer control individuals recruited from two hospitals, the assay detected 52-81% of the patients at disease stages IA to III with a specificity of 96% (95% confidence interval (CI) 93-98%). In a subgroup of 115 individuals, the assay identified, at 100% specificity (95% CI 91-100%), nearly twice as many patients with cancer as those identified by ultradeep mutation sequencing analysis. The low amounts of ctDNA permitted by machine-learning-aided deep methylation sequencing could provide advantages in cancer screening and the assessment of treatment efficacy.
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http://dx.doi.org/10.1038/s41551-021-00746-5DOI Listing
June 2021

Amplified and label-free electrochemical detection of a protease biomarker by integrating proteolysis-triggered transcription.

Biosens Bioelectron 2021 Oct 5;190:113372. Epub 2021 Jun 5.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Hunan Provincial Key Laboratory of Biomacromolecular Chemical Biology, Hunan University, Changsha, 410082, PR China.

Cell-free synthetic biology provides a promising strategy for developing high-performance biosensors by integrating with advanced testing technologies. However, the combination of synthetic biology with electrochemical testing techniques is still underdeveloped. Here, we proposed an electrochemical biosensor for the label-free and ultrasensitive detection of target protease biomarker by coupling a protease-responsive RNA polymerase (PR) for signal amplification. Taking tumor biomarker matrix metalloprotease-2 (MMP-2) as a model protease, we employed PR to transduce each proteolysis reaction mediated by MMP-2 into multiple programmable RNA outputs that can be captured by the DNA probes immobilized on a gold electrode. Moreover, the captured RNAs are designed to contain a guanine-rich sequence that can form G-quadruplex and bind to hemin in the presence of potassium ions. In this scenario, the activity of MMP-2 is converted and amplified into the electrochemical signals of hemin. Under the optimal conditions, this PR-based electrochemical biosensor enabled the sensitive detection of MMP-2 in a wide linear dynamic range from 10 fM to 1.0 nM, with a limit of detection of 7.1 fM. Moreover, the proposed biosensor was further applied in evaluating MMP-2 activities in different cell cultures and human tissue samples, demonstrating its potential in the analysis of protease biomarkers in complex clinical samples.
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http://dx.doi.org/10.1016/j.bios.2021.113372DOI Listing
October 2021

Retraction notice to MicroRNA-539 Inhibits the Epithelial-Mesenchymal Transition of Esophageal Cancer Cells by Twist-Related Protein 1-Mediated Modulation of Melanoma-Associated Antigen A4 [Oncology Research 26(4) (2018) 529-536].

Oncol Res 2021 Jun;28(6):686

Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical SciencesBeijingP.R. China.

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http://dx.doi.org/10.3727/096504020X16231418632584DOI Listing
June 2021

Systematic screening reveals synergistic interactions that overcome MAPK inhibitor resistance in cancer cells.

Cancer Biol Med 2021 Jun 9. Epub 2021 Jun 9.

Department of Cell Biology, Basic Medical College, Army Medical University (Third Military Medical University), Chongqing 400038, China.

Objective: Effective adjuvant therapeutic strategies are urgently needed to overcome MAPK inhibitor (MAPKi) resistance, which is one of the most common forms of resistance that has emerged in many types of cancers. Here, we aimed to systematically identify the genetic interactions underlying MAPKi resistance, and to further investigate the mechanisms that produce the genetic interactions that generate synergistic MAPKi resistance.

Methods: We conducted a comprehensive pair-wise sgRNA-based high-throughput screening assay to identify synergistic interactions that sensitized cancer cells to MAPKi, and validated 3 genetic combinations through competitive growth, cell viability, and spheroid formation assays. We next conducted Kaplan-Meier survival analysis based on The Cancer Genome Atlas database and conducted immunohistochemistry to determine the clinical relevance of these synergistic combinations. We also investigated the MAPKi resistance mechanisms of these validated synergistic combinations by using co-immunoprecipitation, Western blot, qRT-PCR, and immunofluorescence assays.

Results: We constructed a systematic interaction network of MAPKi resistance and identified 3 novel synergistic combinations that effectively targeted MAPKi resistance ( + + , and + ). We next analyzed their clinical relevance and the mechanisms by which they sensitized cancer cells to MAPKi exposure. Specifically, we discovered a novel protein complex, HDGF-LGR5, that adaptively responded to MAPKi to enhance cancer cell stemness, which was up- or downregulated by the inhibitors of ITGB3 + JNK or ITGB3 + IGF1R.

Conclusions: Pair-wise sgRNA library screening provided systematic insights into elucidating MAPKi resistance in cancer cells. ITGB3- + IGF1R-targeting drugs (cilengitide + linsitinib) could be used as an effective therapy for suppressing the adaptive formation of the HDGF-LGR5 protein complex, which enhanced cancer stemness during MAPKi stress.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0560DOI Listing
June 2021

Pathological complete response to neoadjuvant ceritinib of a crizotinib-resistant, stage IIIB non-small cell lung cancer with ALK rearrangement: A case report.

Thorac Cancer 2021 07 9;12(14):2130-2133. Epub 2021 Jun 9.

Department of Thoracic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

The treatment of stage IIIB non-small cell lung cancer (NSCLC) is complicated, the best strategy is chosen individually and surgery is usually not recommended. A 50-year-old female was diagnosed with locally advanced lung adenocarcinoma (stage IIIB, T2bN3M0). Fluorescence in situ hybridization (FISH) analysis revealed an ALK rearrangement. Crizotinib was administered and progression was seen after five months. The patient then received ceritinib with a palliative intent, which led to downstaging (IIIA[N2]) with a radiological and metabolic response. Right lower lobe lobectomy was performed at 12 months post-surgery, and the patient is still disease-free according to the last computed tomography (CT) scan. The unintended downstaging from ceritinib provided a chance for resection in our patient who had ALK-positive stage IIIB NSCLC after the failure of first-line crizotinib, indicating potential usage of ceritinib in the neoadjuvant setting. Future perspective trials are warranted to investigate the role of ceritinib in earlier stages as a primary drug.
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http://dx.doi.org/10.1111/1759-7714.14045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287007PMC
July 2021

Neutrophil to Lymphocyte Ratio Is Increased and Associated With Left Ventricular Diastolic Function in Newly Diagnosed Essential Hypertension Children.

Front Pediatr 2021 19;9:576005. Epub 2021 May 19.

Department of Cardiology, Children's Hospital of Soochow University, Suzhou, China.

Hypertension is associated with cardiac structural and functional changes, including left ventricular hypertrophy (LVH) and LV systolic dysfunction diastolic dysfunction. Neutrophil-to-lymphocyte ratio (NLR) is a novel inflammatory biomarker associated with cardiovascular diseases. The current study aimed to evaluate NLR in children with newly diagnosed essential hypertension and its relationship between blood pressure and cardiac changes. Sixty-five children with newly diagnosed essential hypertension and 54 healthy children were included. Clinical characteristics, blood cell counts, and biochemical parameters were collected. LVH was assessed by calculation of LV mass index (LVMI), and LV systolic function was evaluated by measuring LV ejection fraction and fractional shortening. LV diastolic function was primarily assessed with E/E' ratio by Doppler and echocardiography. The hypertension children had significantly higher LVMI and E/E' ratio than the controls, whereas there was no difference in LV systolic function between the two groups. The NLR was significantly higher in the hypertension group than the control group. Moreover, NLR was positively correlated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels in the hypertension group. Additionally, a significantly positive correlation between NLR and E/E' ratio was found in the hypertension group. However, NLR was not related to LVH and LV systolic function indicators in hypertension children. NLR is elevated in hypertension children, and it is associated positively with office blood pressure levels. Moreover, NLR may help assess LV diastolic function in hypertension children.
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http://dx.doi.org/10.3389/fped.2021.576005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169980PMC
May 2021

Effects of extract on lung adenocarcinoma.

Exp Ther Med 2021 Aug 25;22(2):794. Epub 2021 May 25.

Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Lung adenocarcinoma is the most common subtype of non-small cell lung carcinoma. Tanshinone I is an important fat-soluble component in the extract of that has been reported to inhibit lung adenocarcinoma cell proliferation. However, no studies have clearly demonstrated changes in lung adenocarcinoma gene expression and signaling pathway enrichment following Tanshinone I treatment. And it remains unclear whether salvianolate has an effect on lung adenocarcinoma. The present study downloaded the GSE9315 dataset from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) and the underlying signaling pathways involved after Tanshinone I administration in the lung adenocarcinoma cell line CL1-5. The results revealed that there were 28 and 102 DEGs in the low dosage group (0.01 and 0.10 µg/ml Tanshinone I) and medium dosage groups (1 and 10 µg/ml Tanshinone I), respectively. In the low dosage group, DEGs were mainly enriched in 'positive regulation of T-helper cell differentiation' and 'protein complex'. In the medium dosage group, 102 DEGs were enriched in 'MAPK cascade' and 'extracellular exosome'. Kyoto Encyclopedia of Genes and Genomes pathway analysis demonstrated enrichment of both groups in the PI3K-Akt signaling pathway. Furthermore, there were nine overlapping DEGs [ADP ribosylation factor-interacting protein 2, chemokine (C-X-C motif) ligand 6, SH2 domain-containing adaptor protein B, Src homology 2 domain-containing transforming protein1, collagen type VI α1 chain, elastin, integrin subunit α, endoplasmic reticulum mannosyl-oligosaccharide 1,2-α-mannosidase and sterile α motif domain-containing 9 like] between the two groups, which serve to be potential targets for the treatment of lung adenocarcinoma. The present study also investigated the possible effects of salvianolate on lung adenocarcinoma using nude mouse xenograft models injected with the A549 cell line. The data revealed that salvianolate not only suppressed lung adenocarcinoma tumor growth of in nude mice, but also downregulated the expression levels of ATP7A and ATP7B, which are important proteins in the tumorigenesis and chemotherapy of lung adenocarcinoma. The present study provided evidence for the potential use of extract for treating lung adenocarcinomas in the clinic.
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http://dx.doi.org/10.3892/etm.2021.10226DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170645PMC
August 2021

Generating Instructive Questions from Multiple Articles to Guide Reading in E-Bibliotherapy.

Sensors (Basel) 2021 May 6;21(9). Epub 2021 May 6.

Centre for Computational Mental Healthcare, Department of Computer Science and Technology, Research Institute of Data Science, Tsinghua University, Beijing 100084, China.

E-Bibliotherapy deals with adolescent psychological stress by manually or automatically recommending multiple reading articles around their stressful events, using electronic devices as a medium. To make E-Bibliotherapy really useful, generating instructive questions before their reading is an important step. Such a question shall (a) attract teens' attention; (b) convey the essential message of the reading materials so as to improve teens' active comprehension; and most importantly (c) highlight teens' stress to enable them to generate emotional resonance and thus willingness to pursue the reading. Therefore in this paper, we propose to generate instructive questions from the multiple recommended articles to guide teens to read. Four solutions based on the neural encoder-decoder model are presented to tackle the task. For model training and testing, we construct a novel large-scale QA dataset named TeenQA, which is specific to adolescent stress. Due to the extensibility of question expressions, we incorporate three groups of automatic evaluation metrics as well as one group of human evaluation metrics to examine the quality of the generated questions. The experimental results show that the proposed Encoder-Decoder with Summary on Contexts with Feature-rich embeddings (ED-SoCF) solution can generate good questions for guiding reading, achieving comparable performance on some semantic similarity metrics with that of humans.
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http://dx.doi.org/10.3390/s21093223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125783PMC
May 2021

Sargahydroquinoic Acid, a Cyclooxygenase-2 Inhibitor, Attenuates Inflammatory Responses by Regulating NF-κB Inactivation and Nrf2 Activation in Lipopolysaccharide-Stimulated Cells.

Inflammation 2021 May 29. Epub 2021 May 29.

Department of Food Science and Nutrition, Pukyong National University, Nam-gu, Busan, 48513, Republic of Korea.

Sargahydroquinoic acid (SHQA) is a major plastoquinone in Sargassum macrocarpum and has shown the capacity to prevent inflammation and oxidative stress. However, the protective mechanisms were unclear. The molecular mechanisms of SHQA on ameliorating inflammation and oxidative stress have been investigated, using lipopolysaccharide (LPS)-stimulated macrophages. SHQA was isolated and purified from S. macrocarpum and the anti-inflammatory mechanisms were explored using LPS-stimulated murine macrophage RAW 264.7 cells. SHQA did not change the expression of cyclooxygenase-2 (COX-2) but inhibited the activity of COX-2. As a result, SHQA significantly diminished the secretions of nitric oxide (NO), prostaglandin E (PGE), and multiple pro-inflammatory cytokines. LPS-induced activation of nuclear factor-κB (NF-κB) was inhibited by SHQA by preventing the degradation of inhibitor κB-α (IκBα). NF-κB activation was also downregulated by the inhibition of Akt phosphorylation in LPS-stimulated cells. Furthermore, SHQA induced the expression of heme oxygenase 1 via Nrf2 activation. These results indicated that SHQA inhibited LPS-induced expressions of inflammatory mediators via suppressing the Akt-mediated NF-κB pathway as well as upregulating the Nrf2/HO-1 pathway. Our findings suggest that SHQA might be a potential therapeutic agent in various inflammatory diseases.
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http://dx.doi.org/10.1007/s10753-021-01488-xDOI Listing
May 2021

Enhancing extracellular production of recombinant proteins in Escherichia coli by co-expressing with a haloarchaeal protein containing a putative LolA-like domain.

Appl Microbiol Biotechnol 2021 Jun 27;105(11):4609-4620. Epub 2021 May 27.

State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, 430072, China.

Escherichia coli represents one of the most widely used hosts for recombinant protein production, but its limited capacity for producing extracellular proteins is often cited as a drawback. NJ7G_0991 is an extracellular protein of the haloarchaeon Natrinema sp. J7-2 and comprises a signal peptide, a putative LolA-like domain, and a C-terminal domain of unknown function. Here, we found that the full-length (0991) and the C-terminal domain-deletion variant (0991ΔC) of NJ7G_0991, but not its signal peptide-deletion variant (0991ΔS), were efficiently released into the culture supernatant of E. coli without extensive cell lysis as determined by β-galactosidase activity assay. After lysozyme treatment, E. coli cells producing 0991 or 0991ΔC, but not 0991ΔS, were converted from rod-shaped forms to spheres, suggesting that the secretion of 0991 or 0991ΔC into the periplasm leads to an increase of outer membrane permeability of E. coli. A pelB signal peptide was fused to the N-terminus of the LolA-like domain, and the resulting variant PelB-0991ΔC could be released into the culture supernatant of E. coli more efficiently than 0991ΔC. By using PelB-0991ΔC as a co-expression partner, the extracellular production level of a recombinant thermostable subtilase WF146 could be enhanced by up to 14-fold, and the extracellular concentration of an active site variant of WF146 (WF146-SA) reached up to 129 mg/l. To the best of our knowledge, this is the first report on archaeal protein-based co-expression system for extracellular production of recombinant proteins in E. coli. KEY POINTS: • The haloarchaeal protein NJ7G_0991 can be efficiently released into the culture supernatant of E. coli. • The recombinant NJ7G_0991 increases the outer membrane permeability of E. coli. • The LolA-like domain of NJ7G_0991 can be used as a co-expression partner to improve extracellular production of recombinant proteins in E. coli.
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http://dx.doi.org/10.1007/s00253-021-11352-5DOI Listing
June 2021

Sargahydroquinoic acid (SHQA) suppresses cellular senescence through Akt/mTOR signaling pathway.

Exp Gerontol 2021 08 20;151:111406. Epub 2021 May 20.

Department of Food Science and Nutrition, Pukyong National University, Daeyeon 3-dong, Nam-gu, Busan 608-737, South Korea. Electronic address:

Aim: The effects of sargahydroquinoic acid (SHQA) on cellular senescence and the underlying mechanisms were investigated using human umbilical vascular endothelial cells (HUVECs).

Methods: SHQA or DMSO was supplemented into the medium. Low dose of HO was used to induce premature senescence. Replicative senescence was achieved by continuously culturing cells until they reached a plateau phase. Senescence biomarkers, including p53, p21, and p16 proteins, and SA-β-Gal activity were measured.

Results: Pretreatment of SHQA significantly suppressed the oxidative stress-induced protein expression of p53, p21, and p16, as well as the activity of SA-β-Gal. Additionally, SHQA also delayed the replicative senescence as indicated by an increased population doubling number, reduced protein expression of p53, p21, and p16, as well as a decreased SA-β-Gal activity. SHQA inhibited the phosphorylation of Akt, mTOR, and downstream targets of mTOR, such as p-S6K, which was elevated by premature senescence and replicative senescence. In the absence of senescence stimuli, SHQA also inhibited the Akt/mTOR signaling pathway and promoted autophagy.

Conclusions: SHQA suppressed senescence induced by oxidative stress and replication through inhibiting the Akt/mTOR pathway. With the potential of acting as an Akt/mTOR inhibitor, SHQA might be useful for developing anti-ageing therapy.
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http://dx.doi.org/10.1016/j.exger.2021.111406DOI Listing
August 2021

LMO3 reprograms visceral adipocyte metabolism during obesity.

J Mol Med (Berl) 2021 Aug 20;99(8):1151-1171. Epub 2021 May 20.

Department of Laboratory Medicine, Medical University of Vienna, 1090, Vienna, Austria.

Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. We recently identified LIM domain only 3 (LMO3) in human mature visceral adipocytes; however, its function in these cells is currently unknown. The aim of this study was to determine the potential involvement of LMO3-dependent pathways in the modulation of key functions of mature adipocytes during obesity. Based on a recently engineered hybrid rAAV serotype Rec2 shown to efficiently transduce both brown adipose tissue (BAT) and white adipose tissue (WAT), we delivered YFP or Lmo3 to epididymal WAT (eWAT) of C57Bl6/J mice on a high-fat diet (HFD). The effects of eWAT transduction on metabolic parameters were evaluated 10 weeks later. To further define the role of LMO3 in insulin-stimulated glucose uptake, insulin signaling, adipocyte bioenergetics, as well as endocrine function, experiments were conducted in 3T3-L1 adipocytes and newly differentiated human primary mature adipocytes, engineered for transient gain or loss of LMO3 expression, respectively. AAV transduction of eWAT results in strong and stable Lmo3 expression specifically in the adipocyte fraction over a course of 10 weeks with HFD feeding. LMO3 expression in eWAT significantly improved insulin sensitivity and healthy visceral adipose tissue expansion in diet-induced obesity, paralleled by increased serum adiponectin. In vitro, LMO3 expression in 3T3-L1 adipocytes increased PPARγ transcriptional activity, insulin-stimulated GLUT4 translocation and glucose uptake, as well as mitochondrial oxidative capacity in addition to fatty acid oxidation. Mechanistically, LMO3 induced the PPARγ coregulator Ncoa1, which was required for LMO3 to enhance glucose uptake and mitochondrial oxidative gene expression. In human mature adipocytes, LMO3 overexpression promoted, while silencing of LMO3 suppressed mitochondrial oxidative capacity. LMO3 expression in visceral adipose tissue regulates multiple genes that preserve adipose tissue functionality during obesity, such as glucose metabolism, insulin sensitivity, mitochondrial function, and adiponectin secretion. Together with increased PPARγ activity and Ncoa1 expression, these gene expression changes promote insulin-induced GLUT4 translocation, glucose uptake in addition to increased mitochondrial oxidative capacity, limiting HFD-induced adipose dysfunction. These data add LMO3 as a novel regulator improving visceral adipose tissue function during obesity. KEY MESSAGES: LMO3 increases beneficial visceral adipose tissue expansion and insulin sensitivity in vivo. LMO3 increases glucose uptake and oxidative mitochondrial activity in adipocytes. LMO3 increases nuclear coactivator 1 (Ncoa1). LMO3-enhanced glucose uptake and mitochondrial gene expression requires Ncoa1.
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http://dx.doi.org/10.1007/s00109-021-02089-9DOI Listing
August 2021

Dual-Mobility Cup Total Hip Arthroplasty for Displaced Femoral Neck Fractures: A Retrospective Study With a Median Follow-Up of 5 Years.

Geriatr Orthop Surg Rehabil 2021 30;12:21514593211013244. Epub 2021 Apr 30.

Department of Urinary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Yuexiu District, Guangzhou, China.

Introduction: Patient outcomes following modern dual-mobility cup total hip arthroplasty (DM-THA) remains a concern. Few reports have focused on the use of modern DM-THA in the setting of Asian populations for displaced osteoporotic femoral neck fractures (FNFs). This study aimed to investigate the outcomes of Chinese population with displaced osteoporotic FNFs initially treated with modern DM-THA.

Materials And Methods: Data from 112 consecutive patients (112 hips) with displaced osteoporotic FNFs initially treated with modern DM-THA during 2011-2018 were retrospectively analyzed. Follow-ups were performed at 3 months, 6 months, 12 months, and then every 1 year after surgery. The primary endpoint was the Harris Hip Score (HHS); the secondary endpoint was the main orthopedic complication rate.

Results: The mean HHS improved from 58.62 (±15.79) prior to surgery to 86.13 (±9.92) at the final follow-up. The main complication rate was 14.2% (16/112). Sixteen complications in 10 patients were recorded. Of the 16 complications, there were 2 (1.7%) cases requiring revision DM-THA, 3 (2.6%) cases of loosening, 2 (1.7%) cases of migration, 3 (2.6%) intra-prosthetic dislocation (IPD), 4 (3.5%) cases of tilting, and 2 (1.7%) cases of severe wear. The need for revision was attributed to prosthesis loosening associated with poor bony quality.

Conclusion: In patients with displaced osteoporotic FNFs, DM-THA may yield favorable functional outcomes and a low rate of main orthopedic complications, in particular, a low dislocation rate.
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http://dx.doi.org/10.1177/21514593211013244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114288PMC
April 2021

Osimertinib versus afatinib in patients with T790M-positive, non-small-cell lung cancer and multiple central nervous system metastases after failure of initial EGFR-TKI treatment.

BMC Pulm Med 2021 May 19;21(1):172. Epub 2021 May 19.

Department of Neurosurgery, The First Affiliated Hospital, Sun Yat-Sen University, No. 58, Zhongshan 2nd Road, Yuexiu District, Guangzhou, 510080, China.

Background: The purpose of this study was to compare the efficacy of osimertinib (OSI) versus afatinib (AFA) in patients with T790M-positive, non-small-cell lung cancer (NSCLC) and multiple central nervous system (CNS) metastases after failure of initial epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) treatment.

Methods: Consecutive patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment were retrospectively identified from our medical institution during 2016-2018 and underwent either oral 80 daily OSI or oral 40 daily AFA every 3 weeks for up to 6 cycles, until disease progression, intolerable adverse events (AEs), or death. The co-primary endpoints were overall survival (OS) and progression-free survival (PFS).

Results: The cohort consisted of 124 patients (OSI: n = 60, mean age = 64.24 years [SD: 12.33]; AFA: n = 64, mean age = 64.13 years [SD: 13.72]). After a median follow-up of 24 months (range, 3 to 28), a significant improvement in OS was detected (hazard ratio [HR] 0.59, 95% confidence interval [CI], 0.39-0.91; p = 0.0160; median, 13.7 months [95% CI, 11.1-14.8] for OSI vs 9.6 months [95% CI, 8.4-10.2] for AFA). The median duration of PFS was significantly longer with OSI than with AFA (HR 0.62; 95% CI, 0.41-0.91; p = 0.014; median, 4.5 months [95% CI, 3.5-5.7] vs 3.9 months [95% CI, 3.1-4.8]). The proportion of grade 3 or higher adverse events (AEs) was lower with OSI (22.4%) than with AFA (39.4%).

Conclusions: In patients with T790M-positive NSCLC and multiple CNS metastases after failure of initial EGFR-TKI treatment, OSI may be associated with significantly improved survival benefit compared with AFA, with a controllable tolerability profile.
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http://dx.doi.org/10.1186/s12890-021-01539-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135149PMC
May 2021

Comparative and quantitative analysis of COVID-19 epidemic interventions in Chinese provinces.

Results Phys 2021 Jun 13;25:104305. Epub 2021 May 13.

NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theragnostic, Harbin Medical University, Harbin, Heilongjiang Province, China.

A mathematical model was developed to evaluate and compare the effects and intensity of the coronavirus disease 2019 prevention and control measures in Chinese provinces. The time course of the disease with government intervention was described using a dynamic model. The estimated government intervention parameters and area difference between with and without intervention were considered as the intervention intensity and effect, respectively. The model of the disease time course without government intervention predicted that by April 30, 2020, about 3.08% of the population would have been diagnosed with coronavirus disease 2019 in China. Guangdong Province averted the most cases. Comprehensive intervention measures, in which social distancing measures may have played a greater role than isolation measures, resulted in reduced infection cases. Shanghai had the highest intervention intensity. In the context of the global coronavirus disease 2019 pandemic, the prevention and control experience of some key areas in China (such as Shanghai and Guangdong) can provide references for outbreak control in many countries.
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http://dx.doi.org/10.1016/j.rinp.2021.104305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117536PMC
June 2021

Targeted delivery of neural progenitor cell-derived extracellular vesicles for anti-inflammation after cerebral ischemia.

Theranostics 2021 19;11(13):6507-6521. Epub 2021 Apr 19.

Department of Neurobiology, Key Laboratory of Human Functional Genomics of Jiangsu, Nanjing Medical University, Nanjing, Jiangsu Province 211166, China.

Ischemic stroke remains a major cause of death, and anti-inflammatory strategies hold great promise for preventing major brain injury during reperfusion. In the past decade, stem cell-derived extracellular vesicles (EVs) have emerged as novel therapeutic effectors in immune modulation. However, the intravenous delivery of EVs into the ischemic brain remains a challenge due to poor targeting of unmodified EVs, and the costs of large-scale production of stem cell-derived EVs hinder their clinical application. EVs were isolated from a human neural progenitor cell line, and their anti-inflammatory effects were verified . To attach targeting ligands onto EVs, we generated a recombinant fusion protein containing the arginine-glycine-aspartic acid (RGD)-4C peptide (ACDCRGDCFC) fused to the phosphatidylserine (PS)-binding domains of lactadherin (C1C2), which readily self-associates onto the EV membrane. Subsequently, in a middle cerebral artery occlusion (MCAO) mouse model, the RGD-C1C2-bound EVs (RGD-EV) were intravenously injected through the tail vein, followed by fluorescence imaging and assessment of proinflammatory cytokines expression and microglia activation. The neural progenitor cell-derived EVs showed intrinsic anti-inflammatory activity. The RGD-EV targeted the lesion region of the ischemic brain after intravenous administration, and resulted in a strong suppression of the inflammatory response. Furthermore, RNA sequencing revealed a set of 7 miRNAs packaged in the EVs inhibited MAPK, an inflammation related pathway. These results point to a rapid and easy strategy to produce targeting EVs and suggest a potential therapeutic agent for ischemic stroke.
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http://dx.doi.org/10.7150/thno.56367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120222PMC
July 2021

Environmental activation of a hypothalamic BDNF-adipocyte IL-15 axis regulates adipose-natural killer cells.

Brain Behav Immun 2021 07 12;95:477-488. Epub 2021 May 12.

The Ohio State University Comprehensive Cancer Center, The James Cancer Hospital and Solove Research Institute, Columbus, OH 43210, United States; Department of Cancer Biology and Genetics, College of Medicine, The Ohio State University, Columbus, OH 43210, United States. Electronic address:

Physical and social environments influence immune homeostasis within adipose tissue, yet the mechanisms remain poorly defined. We report that an enriched environment (EE) housing modulates the immune cell population in white adipose tissue of mice including an increase in the abundance of natural killer (NK) cells. EE upregulates the expression of IL-15 and its receptor IL-15Rα specifically within mature adipocytes. Mechanistically, we show that hypothalamic brain-derived neurotrophic factor (BDNF) upregulates IL-15 production in adipocytes via sympathetic β-adrenergic signaling. Overexpressing BDNF mediated by recombinant adeno-associated virus (rAAV) vector in the hypothalamus expands adipose NK cells. Conversely, inhibition of hypothalamic BDNF signaling via gene transfer of a dominant negative TrkB receptor suppresses adipose NK cells. In white adipose tissue, overexpression of IL-15 using an adipocyte-specific rAAV vector stimulates adipose NK cells and inhibits the progression of subcutaneous melanoma, whereas local IL-15 knockdown blocks the EE effect. These results suggest that bio-behavioral factors regulate adipose NK cells via a hypothalamic BDNF-sympathoneural-adipocyte IL-15 axis. Targeting this pathway may have therapeutic significance for cancer.
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http://dx.doi.org/10.1016/j.bbi.2021.05.005DOI Listing
July 2021

Biochemical and metabolic responses of the deep-sea mussel Bathymodiolus platifrons to cadmium and copper exposure.

Aquat Toxicol 2021 Jul 2;236:105845. Epub 2021 May 2.

Center of Deep Sea Research, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China; CAS Key Laboratory of Marine Ecology and Environmental Sciences, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China; University of Chinese Academy of Sciences, Beijing 10049, China. Electronic address:

Greater interest in commercial deep-sea mining has been accompanied by mounting environmental concerns, including metal contamination resulting from mining activities. However, little is known about the toxic effects of metal exposure on deep-sea life. Given its ability to accumulate metals from the surrounding environment, its wide distribution at both vents and seeps, and its high abundance, the deep-sea mussel Bathymodiolus platifrons could serve as an ideal model to investigate the toxicological responses of deep-sea organisms to metal exposure. Here, we evaluated metal accumulation, traditional metal-related biomarkers, namely acid phosphatase (ACP), alkaline phosphatase (AKP), superoxide dismutase, catalase, reduced glutathione, metallothioneins, and malondialdehyde, as well as metabolic profiles in the gills of B. platifrons after a 7-day exposure to copper (100 μg/L), cadmium (500 μg/L), or copper-plus-cadmium treatments (100 μg/L Cu and 500 μg/L Cd). Metal exposure concentrations selected in this study can be found in deep-sea hydrothermal environments. Metal exposure resulted in significant metal accumulation in the gills of the mussel, indicating that B. platifrons has promise for use as an indicator of deep-sea metal pollution levels. Traditional biomarkers (AKP, ACP, and measured antioxidants) revealed cellular injury and oxidative stress in mussels following metal exposure. Metabolic responses in the three treatment groups indicated that metal exposure perturbed osmoregulation, energy metabolism, and nucleotide metabolism in mussels, in a response marked by differentially altered levels of amino acids, hypotaurine, betaine, succinate, glucose 6-phosphate, fructose 6-phosphate, guanosine, guanosine 5'-monophosphate, and inosine. Nevertheless, several uniquely altered metabolites were found in each treatment exposure group, suggesting dissimilar modes of toxicity between the two metal types. In the Cd-exposed group, the monosaccharide D-allose, which is involved in suppressing mitochondrial ROS production, was downregulated, a response consistent with oxidative stress in Cd-exposed B. platifrons. In the Cu-exposed group, the detected alterations in dopamine, dopamine-related, and serotonin-related metabolites together suggest disturbed neurotransmission in Cu-exposed B. platifrons. In the Cu-plus-Cd group, we detected a decline in fatty acid levels, implying that exposure to both metals jointly exerted a negative influence on the physiological functioning of the mussel. To the best of our knowledge, this is the first study to investigate changes in metabolite profiles in Bathymodiolus mussels exposed to metal. The findings reported here advance our understanding of the adverse impact of metal exposure on deep-sea life and can inform deep-sea mining assessments through the use of multiple biomarkers.
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http://dx.doi.org/10.1016/j.aquatox.2021.105845DOI Listing
July 2021

SARS-CoV-2 promote autophagy to suppress type I interferon response.

Signal Transduct Target Ther 2021 05 8;6(1):180. Epub 2021 May 8.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, China.

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http://dx.doi.org/10.1038/s41392-021-00574-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105701PMC
May 2021
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