Publications by authors named "Jun Chen"

4,891 Publications

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A comparison of the effects of fire needle and routine acupuncture for myofascitis: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jun;100(23):e25473

Jiangxi University of Traditional Chinese Medicine, Nanchang, PR China.

Background: Myofascitis is a common disease in clinic. The main cause of the disease is aseptic inflammation of local muscles and connective tissues such as myofascial, which can be manifested as paralysis, distension, and other discomfort, local muscle stiffness, spasm or palpable strain-like nodules. Chinese medicine ascribes it to "bi disease" and "Arthralgia disease," while Western medicine believes that the disease is mainly due to local muscle and fascia edema and exudation caused by trauma or long-term strain, forcing nerves to jam and producing pain and other abnormal feelings. Although the disease is not life-threatening, the pain and distension caused by local inflammatory stimuli can affect the patient's daily life and sleep quality. The purpose of this systematic review is to evaluate the efficacy of fire needle vs routine acupuncture in the treatment of myofascitis.

Methods: Randomized controlled trials (RCTS) of fire needle vs routine acupuncture for myofascial inflammation will be comprehensively searched from inception to September 2020 on PubMed, Embase, Cochrane Library, China Biomedical Literature (CBM), China National Knowledge Infrastructure (CNKI), Chongqing VIP (CQVIP), and Wanfang. Additionally, RCT registered sites, including http://www.ClinicalTrials.gov and http://www.chictr.org.cn, also will be the search. Visual analogue scale (VAS) was used to score the pain before and after treatment. The primary outcome will be to compare the difference in pain scores between the 2 interventions. Two independent authors filtered the literature in the above database, extracted the data, and cross-checked it.

Results: This study will offer a reasonable comprehensive evidence for the treatment of myofascitis with fire needle.

Conclusion: The conclusion of this study will provide evidence to judge the effectiveness of fire needle on myofascitis.

Registration Number: INPLASY202080034.
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http://dx.doi.org/10.1097/MD.0000000000025473DOI Listing
June 2021

Anti-inflammatory effects of paeoniflorin caused by regulation of the hif1a/miR-210/caspase1/GSDMD signaling pathway in astrocytes: a novel strategy for hypoxia-induced brain injury in rats.

Immunopharmacol Immunotoxicol 2021 Jun 11:1-9. Epub 2021 Jun 11.

The First Clinical Medical College, Lanzhou University, Lanzhou, China.

Hypoxia-induced injury is a classic symptom of obstructive sleep apnea hypopnea syndrome (OSAHS), which is a risk factor of various diseases, such as hypertension, heart failure and stroke. However, there is no effective therapy for hypoxia-induced injury or OSAHS due to the elusive mechanism involved. This study aimed to assess the effects of paeoniflorin on hypoxia-induced injury and explore the underlying mechanism. Hypoxic models of SD rats and CTX-TNA2 cells were used to assess the effect of paeoniflorin, and the expressions of hif1a, miR-210, caspase1 and GSDMD were detected using western blots and RT-PCR. Plasmid transfection was performed to explore the role of miR-210 in the effect of paeoniflorin. Firstly, we confirmed that hypoxia induced severe neuronal injury and an enhancement of inflammation in the rat brain, with elevated expression of caspase1, IL1b and IL18. In addition, the results showed an activation of astrocytes and an increased level of pyroptosis under hypoxic conditions, which suggested a critical role of pyroptosis in hypoxiainduced injury of the brain. Furthermore, we found that compared with the controls, paeoniflorin treatment improved hypoxia-induced pyroptosis in astrocytes. Moreover, we detected the activation of hif1a/miR-210 signaling in the effects of paeoniflorin on astrocytes. As expected, the expression of hif1a and miR-210 was significantly upregulated in astrocytes when exposed to hypoxia, while paeoniflorin treatment reversed these enhancements. After transfection of miR-210 mimics, the attenuation of pyroptosis induced by paeoniflorin was suppressed, which was accompanied by an increase of ROS levels, as well as LDH release, indicating a critical role of miR-210 in pyroptosis in astrocytes. Our findings demonstrated that paeoniflorin improved hypoxia-induced pyroptosis in astrocytes via depressing hif1a/miR-210/caspase1/GSDMD signaling, providing robust evidence for the treatment of hypoxic injury and OSAHS.HighlightsHypoxia induces severe injury and inflammatory response in the rat brain;Hypoxia enhanced pyroptotic level and led to an activation of astrocytes.;Paeoniflorin alleviates hypoxia-induced pyroptosis in astrocytes;Transfection of miR-210 mimics suppressed the effects of paeoniflorin on hypoxia-induced pyroptosis in astrocytes.
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http://dx.doi.org/10.1080/08923973.2021.1924194DOI Listing
June 2021

Immunotherapy versus standard chemotherapy for treatment of extensive-stage small-cell lung cancer: a systematic review.

Immunotherapy 2021 Jun 11. Epub 2021 Jun 11.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Anshan Road No. 154, Heping District, Tianjin, 300052, China.

We conducted a systematic review and network meta-analysis to evaluate the efficacy of immunotherapy versus chemotherapy to treat extensive-stage small-cell lung cancer. We analyzed several eligible clinical trials using fixed or random-effects models to evaluate relative treatment effects depending on heterogeneity. In the experimental group, immunotherapy showed significant improvement in overall survival (hazard ratio [HR]: 0.82; 95% CI: 0.74-0.89; I = 31.4%; p < 0.001) and progression-free survival (HR: 0.77; 95% CI: 0.80-0.83; I = 22.7%; p < 0.001). Immunotherapy is likely to significantly improve extensive-stage small-cell lung cancer patients' overall survival and progression-free survival compared with standard chemotherapy. Anti-PD L1 exhibited superior overall survival compared with anti-PD 1 and anti-CTLA4.
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http://dx.doi.org/10.2217/imt-2020-0284DOI Listing
June 2021

Effects of preserving the bronchial artery on cough after thoracoscopic lobectomy.

Thorac Cancer 2021 Jun 10. Epub 2021 Jun 10.

Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou, China.

Background: The purpose of this prospective study was to explore the influence of both preoperative three-dimensional (3D) reconstruction and intraoperative preservation of the bronchial artery (BA) on postoperative cough after thoracoscopic lobectomy.

Methods: A total of 60 patients who had received a combination of thoracoscopic lobectomy and systematic lymph node dissection were included in this study. They were divided into two groups, namely the BA preservation group (Group A), and conventional surgical treatment group (Group B). In group A, we used Exoview software for 3D reconstruction of the BA before the operation and the BA was preserved during the operation. 3D reconstruction of the BA was not performed before surgery in group B. The incidence of postoperative cough, the Mandarin Chinese version of the Leicester cough questionnaire (LCQ-MC), physiological, psychological and social dimensions and total score of the two groups were compared and analyzed.

Results: The scores and total scores of LCQ-MC in group B were lower than those in group A one and two months after surgery. There were significant differences between the two groups in physiological and psychological dimensions and total scores (p < 0.05), but there was no significant difference in social dimension between the two groups (p > 0.05). The incidence of postoperative cough in group A (16.7%) was lower than that in group B (30%), while the difference was not statistically significant (p = 0.222).

Conclusions: Preoperative 3D reconstruction and intraoperative preservation of the BA can reduce the severity of postoperative cough.
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http://dx.doi.org/10.1111/1759-7714.14012DOI Listing
June 2021

Influence of early thermal-oxidative ageing on the structure and properties of polyoxymethylene copolymer.

R Soc Open Sci 2021 Jun 9;8(6):210034. Epub 2021 Jun 9.

Department of Polymer Processing and Engineering, College of Polymer Science and Engineering, Sichuan University, Chengdu, Sichuan 610065, People's Republic of China.

Thermal-oxidative ageing of polyoxymethylene (POM) copolymer in the oven at 100°C for 1, 2, 3, 5, 7, 10, 14 and 21 days and the influence of early thermal-oxidative ageing on POM structure and properties were studied by means of wide-angle X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry and tensile test. Based on the results, we found that the early thermal-oxidative ageing of POM copolymer can be divided into three regions. The region I is the initial 3 days. In this region, some molecular chains rearranged, resulting in internal stress relaxation, increase of crystallinity degree and grain size due to the perfection of crystal structure; both extended chain crystal (ECC) and folded chain crystal (FCC) increased and ECC grew faster than FCC. The region II is from 3 days to 10 days, and in this region, chain scission took place in amorphous region and led to chemi-crystallization. The region III is after 10 days. In this region, the structure and performance of POM copolymer reached a stable situation at this stage. In this work, the difference between skin and core were also analysed.
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http://dx.doi.org/10.1098/rsos.210034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188004PMC
June 2021

Effects of elevated sulfate in eutrophic waters on the internal phosphate release under oxic conditions across the sediment-water interface.

Sci Total Environ 2021 May 29;790:148010. Epub 2021 May 29.

Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; School of Animal, Rural and Environmental Sciences, Nottingham Trent University, Brackenhurst Campus, NG25 0QF, UK; Integrated Water-Energy-Food Facility (iWEF), Nottingham Trent University, Nottinghamshire NG25 0QF, UK; Nanjing Xianglai Academy of Eco-environmental Science and Technology, Nanjing 210046, China. Electronic address:

Eutrophication in freshwater environments may be enhanced by the elevation of sulfate in waters, through the release of internal phosphorus (P) from anoxic sediments. However, the influence of increasing but modest sulfate concentrations (less than 3000 μM) on P release under oxic conditions across the sediment-water interface (SWI) in eutrophic freshwater is poorly understood. In this study, the profiles of P, iron (Fe), sulfur (S) and physicochemical parameters were measured in a simulated lacustrine system with varying concentrations of sulfate (970-2600 μM) in overlying water. The results indicated that elevated concentrations of sulfate increased the soluble reactive P in overlying waters under oxic conditions across the SWI. A 100 μM increase of sulfate was found to induce a 0.128 mgmd increase of P flux from surface sediments into overlying waters under oxic conditions. Higher sulfate concentrations in the overlying waters increased the concentrations of labile S(-II) in the deep sediments, due to sulfate penetration and subsequent reduction to S(-II). We also found the fluxes of labile Fe (10.34 to 18.33 mgmd) and P (2.70 to 1.33 mgmd) from deep to surface sediment were both positive and greater than the corresponding fluxes (Fe, 2.2 to 3.51 and P, 2.6 to 0.39 mgmd, respectively) from surface sediment to the overlying water, suggesting that reduction of P-bearing Fe(III)(oxyhydr)oxides in deep anoxic sediment acted as a major source of internal P release. In addition, the upward flux of Fe(II) was significantly lower under higher sulfate conditions, indicating that the Fe(II) flux could be mitigated by formation of Fe(II) sulfides in the deep sediment. Under these conditions, less Fe(II) from deep sediments could be re-oxidized and combine with P in the surface, oxic sediment, thereby reducing the retention capacity for P and leading to higher release of internal P to the water column.
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http://dx.doi.org/10.1016/j.scitotenv.2021.148010DOI Listing
May 2021

Self-Assembling Porphyrins as a Single Therapeutic Agent for Synergistic Cancer Therapy: A One Stone Three Birds Strategy.

ACS Appl Mater Interfaces 2021 Jun 10. Epub 2021 Jun 10.

Pharmaceutical Engineering Research Center, College of Pharmacy, Chongqing Medical University, Chongqing 400000, China.

Combining photodynamic therapy (PDT), chemodynamic therapy (CDT), and ferroptosis is a valuable means for an enhanced anticancer effect. However, traditional combination of PDT/CDT/ferroptosis faces several hurdles, including excess glutathione (GSH) neutralization and preparation complexity. In this work, a versatile multifunctional nanoparticle (HCNP) self-assembled from two porphyrin molecules, chlorin e6 and hemin, is developed. The as-constructed HCNPs exhibit a peroxidase-mimic catalytic activity, which can lead to the in situ generation of endogenous O, thereby enhancing the efficacy of PDT. Furthermore, the generation of hydroxyl radicals (OH) in the tumor environment in reaction to the high level of HO and the simultaneous disruption of intracellular GSH endow the HCNPs with the capacity of enhanced CDT, resulting in a more effective therapeutic outcome in combination with PDT. More importantly, GSH depletion further leads to the inactivation of GSH peroxide 4 and induced ferroptosis. Both in vitro and in vivo results showed that the combination of PDT/CDT/ferroptosis realizes highest antitumor efficacy significantly under laser irradiation. Therefore, by integrating the superiorities of O and OH generation capacity, GSH-depletion effect, and bioimaging into a single nanosystem, the HCNPs are a promising single therapeutic agent for tumor PDT/CDT/ferroptosis combination therapy.
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http://dx.doi.org/10.1021/acsami.1c04868DOI Listing
June 2021

Novel Affibody Molecules Targeting the HPV16 E6 Oncoprotein Inhibited the Proliferation of Cervical Cancer Cells.

Front Cell Dev Biol 2021 24;9:677867. Epub 2021 May 24.

Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.

Despite prophylactic vaccination campaigns, high-risk human papillomavirus (HPV)-induced cervical cancer remains a significant health threat among women, especially in developing countries. The initial occurrence and consequent progression of this cancer type primarily rely on, E6 and E7, two key viral oncogenes expressed constitutively, inducing carcinogenesis. Thus, E6/E7 have been proposed as ideal targets for HPV-related cancer diagnosis and treatment. In this study, three novel HPV16 E6-binding affibody molecules (Z1115, Z1171, and Z1235) were isolated from a randomized phage display library and cloned for bacterial production. These affibody molecules showed high binding affinity and specificity for recombinant and native HPV16 E6 as determined by surface plasmon resonance, indirect immunofluorescence, immunohistochemistry, and near-infrared small animal optical imaging and . Moreover, by binding to HPV16 E6 protein, Z1235 blocked E6-mediated p53 degradation, which increased the expression of some key p53 target genes, including BAX, PUMA and p21, and thereby selectively reduced the viability and proliferation of HPV16-positive cells. Importantly, Z1235 was applied in combination with HPV16 E7-binding affibody Z384 to simultaneously target the HPV16 E6/E7 oncoproteins, and this combination inhibited cell proliferation more potently than either modality alone. Mechanistic studies revealed that the synergistic antiproliferative activity depends primarily on the induction of cell apoptosis and senescence but not cell cycle arrest. Our findings provide strong evidence that three novel HPV16 E6-binding affibody molecules could form a novel basis for the development of rational strategies for molecular imaging and targeted therapy in HPV16-positive preneoplastic and neoplastic lesions.
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http://dx.doi.org/10.3389/fcell.2021.677867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181454PMC
May 2021

Soluble CD163 Identifies Those at Risk for Increased Hepatic Inflammation & Fibrosis.

Open Forum Infect Dis 2021 Jun 22;8(6):ofab203. Epub 2021 Apr 22.

Florida International University, Miami, Florida, USA.

Background: Liver disease remains a significant cause of morbidity and mortality in HIV-infected persons. Soluble CD163 is a marker of Kupffer cell activation that is highly associated with development of hepatic fibrosis. The relative contributions of HIV-associated systemic immune activation vs other etiologies of injury are poorly characterized.

Methods: We utilized subjects in the Miami Adult Studies on HIV (MASH) cohort to evaluate 464 participants including 361 people with HIV (PWH) and 103 hepatitis C virus (HCV)/HIV-uninfected controls. Subjects underwent testing for hepatic fibrosis using both magnetic resonance elastography and the Enhanced Liver Fibrosis Index. Steatosis was evaluated by magnetic resonance imaging-derived proton density fat fraction. Immune activation markers and cytokines were quantitated using Luminex methodologies.

Results: Participants with HIV with or without HCV coinfection had higher levels of sCD163 than uninfected controls ( < .05). Soluble sCD163 was highly associated with elevated alanine aminotransferase, a key marker of inflammation/injury and with hepatic fibrosis. Hepatic steatosis was also associated with a cytokine pattern suggestive of Kupffer cell activation but was not associated with an increase in sCD14 or sCD27.

Conclusions: Injury and resultant hepatic fibrosis occur by distinct though overlapping mechanistic pathways. In PWH, sCD163 is highly associated with both injury and fibrosis, suggesting that persistent systemic immune activation is a major contributor to long-term outcomes, adding to damage caused by alcohol, steatosis, and other hepatotoxic drug effects.
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http://dx.doi.org/10.1093/ofid/ofab203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180248PMC
June 2021

Treatment of intractable hiccups using combined cervical vagus nerve and phrenic nerve blocks ultrasound guidance.

Minerva Anestesiol 2021 Jun 8. Epub 2021 Jun 8.

Department of Anesthesiology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, China -

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http://dx.doi.org/10.23736/S0375-9393.21.15680-9DOI Listing
June 2021

Kinetically Controlled Self-Assembly of Binary Polymer-Grafted Nanocrystals into Ordered Superstructures via Solvent Vapor Annealing.

Nano Lett 2021 Jun 8. Epub 2021 Jun 8.

Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States.

Polymer-inorganic nanocomposites based on polymer-grafted nanocrystals (PGNCs) are enabling technologically relevant applications owing to their unique physical, chemical, and mechanical properties. While diverse PGNC superstructures have been realized through evaporation-driven self-assembly, this approach presents multifaceted challenges in experimentally probing and controlling assembly kinetics. Here, we report a kinetically controlled assembly of binary superstructures from a homogeneous disordered PGNC mixture utilizing solvent vapor annealing (SVA). Using a NaZn-type superstructure as a model system, we demonstrate that varying the solvent vapor pressure during SVA allows for exquisite control of the rate and extent of PGNC assembly, providing access to nearly complete kinetic pathways of binary PGNC crystallization. Characterization of kinetically arrested intermediates reveals that assembly follows a multistep crystallization pathway involving spinodal-like preordering of PGNCs prior to NaZn nucleation. Our work opens up new avenues for the synthesis of multicomponent PGNC superstructures exhibiting multifunctionalities and emergent properties through a thorough understanding of kinetic pathways.
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http://dx.doi.org/10.1021/acs.nanolett.1c00890DOI Listing
June 2021

Improved Stability Criteria for Discrete-Time Delayed Neural Networks via Novel Lyapunov-Krasovskii Functionals.

IEEE Trans Cybern 2021 Jun 7;PP. Epub 2021 Jun 7.

This article investigates the stability problem for discrete-time neural networks with a time-varying delay by focusing on developing new Lyapunov-Krasovskii (L-K) functionals. A novel L-K functional is deliberately tailored from two aspects: 1) the quadratic term and 2) the single-summation term. When the variation of the discrete-time delay is further considered, the constant matrix involved in the quadratic term is extended to be a delay-dependent one. All these innovations make a contribution to a quadratic function with respect to the delay from the forward differences of L-K functionals. Consequently, tractable stability criteria are derived that are shown to be more relaxed than existing results via numerical examples.
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http://dx.doi.org/10.1109/TCYB.2021.3076196DOI Listing
June 2021

Sex-Based Differences in Clinical Outcomes After Arthroscopic Anterior Shoulder Stabilization: Results at 5-Year Follow-up.

Orthop J Sports Med 2021 May 20;9(5):23259671211008841. Epub 2021 May 20.

Sports Medicine Institute, Department of Sports Medicine and Arthroscopy, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

Background: The influence of patient sex on clinical outcomes after arthroscopic anterior shoulder stabilization is unclear.

Purpose: To investigate sex-based differences in clinical outcomes after arthroscopic anterior shoulder stabilization.

Study Design: Cohort study; Level of evidence, 3.

Methods: A retrospective study was conducted among 76 patients who underwent arthroscopic anterior shoulder stabilization from February 2010 to December 2017. The patients were grouped by sex. The recurrence rate of instability was compared, as were pre- and postoperative pain scores, functional outcome scores, and active range of motion (ROM). Postoperative magnetic resonance imaging (MRI) was also performed for structural assessment of the glenohumeral joint.

Results: No significant difference was found in the recurrence rate between female and male patients (13.3% vs 14.8%; ≥ .999; risk ratio, 1.107 [95% CI, 0.266-4.597]). Compared with male patients, female patients had a significantly lower preoperative Constant score (94.4 ± 6.4 vs 85.4 ± 11.1; = .002), forward flexion (173.8° ± 10.7° vs 154.0° ± 33.8°; = .011), abduction (171.0° ± 18.4° vs 142.7° ± 39.9°; = .001), and external rotation (76.6° ± 21.6° vs 67.7° ± 20.4°; = .037). Postoperatively, female patients had a significantly lower Simple Shoulder Test score compared with men (8.8 ± 1.9 vs 10.3 ± 1.6; = .005). The mean changes from pre- to postoperative Rowe score (43.6 ± 21.4 vs 31.5 ± 19.8; = .044), Constant score (9.9 ± 8.9 vs 0.8 ± 8.1; = .002), forward flexion (24.0 ± 36.2 vs 4.2 ± 10.9; = .013), abduction (36.0 ± 38.3 vs 7.6 ± 18.4; < .001), and external rotation (19.7 ± 21.3 vs 6.7 ± 26.2; = .023) in female patients were significantly higher than those in the men. There were no sex-based differences on any MRI parameter measured.

Conclusion: Female patients had a similar recurrence rate as that of male patients after arthroscopic anterior shoulder stabilization. Most postoperative clinical outcome measures showed no significant difference between the sexes. Despite worse preoperative values, more significant improvements in postoperative shoulder function and active ROM were seen in women.
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http://dx.doi.org/10.1177/23259671211008841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142006PMC
May 2021

Electrodeposition of (hydro)oxides for an oxygen evolution electrode.

Chem Sci 2020 Apr 20;11(39):10614-10625. Epub 2020 Apr 20.

Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), Renewable Energy Conversion and Storage Center, College of Chemistry, Nankai University Tianjin 300071 China

Electrochemical water splitting is a promising technology for hydrogen production and sustainable energy conversion, but the electrolyzers that are currently available do not have anodic electrodes that are robust enough and highly active for the oxygen evolution reaction (OER). Electrodeposition provides a feasible route for preparing freestanding OER electrodes with high active site utilization, fast mass transport and a simple fabrication process, which is highly attractive from both academic and commercial points of view. This minireview focuses on the recent electrodeposition strategies for metal (hydro)oxide design and water oxidation applications. First, the intrinsic advantages of electrodeposition in comparison with traditional technologies are introduced. Then, the unique properties and underlying principles of electrodeposited metal (hydro)oxides in the OER are unveiled. In parallel, illustrative examples of the latest advances in materials structural design, controllable synthesis, and mechanism understanding through the electrochemical synthesis of (hydro)oxides are presented. Finally, the latest representative OER mechanism and electrodeposition routes for OER catalysts are briefly overviewed. Such observations provide new insights into freestanding (hydro)oxides electrodes prepared electrodeposition, which show significant practical application potential in water splitting devices. We hope that this review will provide inspiration for researchers and stimulate the development of water splitting technology.
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http://dx.doi.org/10.1039/d0sc01532fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162381PMC
April 2020

Testing for mediation effect with application to human microbiome data.

Stat Biosci 2021 Jul 27;13(2):313-328. Epub 2019 Jul 27.

Division of Biostatistics, Washington University in St. Louis, St. Louis, MO 63110, USA.

Mediation analysis has been commonly used to study the effect of an exposure on an outcome through a mediator. In this paper, we are interested in exploring the mediation mechanism of microbiome, whose special features make the analysis challenging. We consider the isometric logratio transformation of the relative abundance as the mediator variable. Then, we present a de-biased Lasso estimate for the mediator of interest and derive its standard error estimator, which can be used to develop a test procedure for the interested mediation effect. Extensive simulation studies are conducted to assess the performance of our method. We apply the proposed approach to test the mediation effect of human gut microbiome between the dietary fiber intake and body mass index.
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http://dx.doi.org/10.1007/s12561-019-09253-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177450PMC
July 2021

Inhibition of p22 Suppresses Epithelial Ovarian Cancer Cell Proliferation and Tumorigenesis.

J Cancer 2021 19;12(14):4277-4287. Epub 2021 May 19.

Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

The aim of this study was to investigate the biological role and molecular mechanism of p22 in epithelial ovarian cancer. Immunohistochemistry was employed to determine the p22 expression level in epithelial ovarian cancer tissues. The effects of p22 on epithelial ovarian cancer cell proliferation, tumorigenesis, and chemosensitivity were evaluated by CCK-8, EdU assay, colony formation and apoptosis assays in vitro and by mouse experiments in vivo. Immunoprecipitation analyses were utilized to explore the potential mechanisms of p22 mediated downstream signaling, and RT-PCR and western blot were used to confirm the relevance. P22 expression could be detected in epithelial ovarian cancer tissues and normal fallopian epithelial cells. Silencing p22 suppressed epithelial ovarian cancer cell proliferation and colony formation capacity , and inhibited the tumor growth in nude mice bearing the A2780 xenograft . Mechanistic investigations showed that p22 regulated proteasome ubiquitination and subsequent proteasome-dependent degradation of p53 in A2780 and U87 cells . Furthermore, knockdown of p22 significantly increased the chemosensitivity of A2780 cells to cisplatin or paclitaxel. These results suggested that p22 as a pivotal oncogene during epithelial ovarian cancer carcinogenesis and p22 inhibition might be a potential therapeutic strategy for epithelial ovarian cancer.
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http://dx.doi.org/10.7150/jca.54163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176422PMC
May 2021

EML4-ALK-mediated activation of the JAK2-STAT pathway is critical for non-small cell lung cancer transformation.

BMC Pulm Med 2021 Jun 6;21(1):190. Epub 2021 Jun 6.

Department of Lung Cancer Surgery, Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.

Background: The echinoderm microtubule-associated protein-like-4 anaplastic lymphoma kinase (EML4-ALK) fusion gene was identified in a subset of non-small cell lung cancer (NSCLC) patients. They responded positively to ALK inhibitors. This study aimed to characterize the mechanisms triggered by EML4-ALK to induce NSCLC transformation.

Methods: HEK293 and NIH3T3 cells were transfected with EML4-ALK variant 3 or pcDNA3.1-NC. H2228 cells were transfected with siRNA-EML4-ALK or siRNA-NC. Cell viability and proliferation were measured by the CCK-8 and EdU methods, respectively. Flow cytometry revealed apoptosis. Gene expression profiles were generated from a signaling pathway screen in EML4-ALK-regulated lung cancer cells and verified by qPCR and Western blotting. The co-immunoprecipitation and immunohistochemistry/ immunofluorescence determined the interaction and colocalization of JAK2-STAT pathway components with EML4-ALK.

Results: Microarray identified several genes involved in the JAK2-STAT pathway. JAK2 and STAT6 were constitutively phosphorylated in H2228 cells. EML4-ALK silencing downregulated phosphorylation of STAT6. Expression of EML4-ALK in HEK293 and NIH3T3 cells activated JAK2, STAT1, STAT3, STAT5, and STAT6. In EML4-ALK-transfected HEK293 cells and EML4-ALK-positive H2228 cells, activated STAT6 and JAK2 colocalized with ALK. STAT3 and STAT6 were phosphorylated and translocated to the nucleus of H2228 cells following IL4 or IL6 treatment. Apoptosis increased, while cell proliferation and DNA replication decreased in H2228 cells following EML4-ALK knockdown. In contrast, HEK293 cell viability increased following EML4-ALK overexpression, while H2228 cell viability significantly decreased after treatment with ALK or JAK-STAT pathway inhibitors.

Conclusions: Our data suggest that the aberrant expression of EML4-ALK leads to JAK2-STAT signaling pathway activation, which is essential for the development of non-small cell lung cancer.
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http://dx.doi.org/10.1186/s12890-021-01553-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180148PMC
June 2021

Generation of an induced pluripotent stem cell line (OGHFUi001-A) from a type 1 early infantile epileptic encephalopathy with ARX mutation.

Stem Cell Res 2021 May 27;53:102367. Epub 2021 Apr 27.

Department of Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200091, People's Republic of China. Electronic address:

Type 1 early infantile epileptic encephalopathy (EIEE1) is a severe early-onset epileptic encephalopathy with arrest of psychomotor development caused by hemizygous mutations in the ARX gene, which encodes a transcription factor in fundamental brain developmental processes. A human induced pluripotent stem cell (iPSC) line, termed as OGHFUi001-A, was generated using non-integrating episomal vector technique from peripheral blood mononuclear cells (PBMCs) of a 7-year-old male EIEE1 patient, who had a hemizygous (c.989G > T: p.R330L) mutation in the ARX gene. OGHFUi001-A offers a useful cell resource to investigate pathogenic mechanisms in EIEE1, as well as a cell-based model for drug development for EIEE1.
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http://dx.doi.org/10.1016/j.scr.2021.102367DOI Listing
May 2021

Comparative efficacy of treatments for previously treated patients with advanced esophageal and esophagogastric junction cancer: A network meta-analysis.

PLoS One 2021 4;16(6):e0252751. Epub 2021 Jun 4.

Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China.

Background: It remains unclear which treatment is the most effective for previously treated patients with advanced esophageal and esophagogastric junction (EGJ) cancer. We conducted a network meta-analysis to address this important issue.

Methods: PubMed, Embase, Cochrane Library, and Web of Science databases were searched for relevant phase II and III randomized controlled trials (RCTs). Overall survival (OS) was the primary outcome of interest, which was reported as hazard ratio (HR) and 95% confidence intervals (CIs).

Results: Sixteen RCTs involving 3372 patients and evaluating 15 treatments were included in this network meta-analysis. Ramucirumab+chemotherapy (CT) (HR = 0.52, 95% CI: 0.35-0.77) and use of programmed death receptor 1 (PD-1) inhibitors, including camrelizumab (HR = 0.71, 95% CI: 0.57-0.88), sintilimab (HR = 0.70, 95% CI: 0.50-0.98), nivolumab (HR = 0.76, 95% CI: 0.62-0.94), and pembrolizumab (HR = 0.84, 95% CI: 0.72-0.98), conferred better OS than CT; however, this OS benefit was not observed for PD-L1 inhibitor (avelumab) and other target agents (trastuzumab, everolimus, gefitinib, and anlotinib). In subgroup analysis, ramucirumab+CT and pembrolizumab showed significant improvement in OS, when compared to CT, in esophageal/EGJ adenocarcinoma (AC) cases; moreover, all PD-1 inhibitors had significant OS advantage over CT in treating esophageal squamous cell carcinoma (SCC). Based on treatment ranking in terms of OS, ramucirumab+CT and camrelizumab were ranked the best treatments for patients with AC and SCC, respectively.

Conclusions: Ramucirumab+CT and PD-1 inhibitors were superior to CT for previously treated cases of advanced esophageal/EGJ cancer. Ramucirumab+CT seemed to be the most effective treatment in patients with esophageal/EGJ AC, while use of PD-1 inhibitors, especially camrelizumab, was likely to be the optimal treatment in patients with esophageal SCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252751PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8177625PMC
June 2021

Diagnostic accuracy of 3D magnetic resonance elastography for assessing histologic grade of hepatocellular carcinoma: comparison of three methods for positioning region of interest.

Abdom Radiol (NY) 2021 Jun 3. Epub 2021 Jun 3.

Department of Radiology, The Third Affiliated Hospital, Sun Yat-Sen University (SYSU), Tianhe Road, No 600, Guangzhou, Guangdong, 510630, People's Republic Of China.

Purpose: To assess the influence of region of interest (ROI) placement on the predictive value of 3D MRE in differentiating the histologic grade of HCC.

Methods: 85 patients with pathologically confirmed HCCs were analyzed using 3D MRE imaging, two radiologists measured the tumor stiffness with three different ROI positioning methods. Intraclass correlation coefficient (ICC) was expressed in terms of inter- and intra-observer agreements. Kruskal-Wallis rank test or one-way ANOVA was used to compare the difference in MRE stiffness across the three-ROI positioning methods. Receiver operating characteristic curve analysis (ROC) was performed, and the area under curve (AUC) was measured to evaluate the diagnostic performance.

Results: There were 64 (75%) well-or-moderately differentiated HCCs and 21(25%) poorly differentiated HCCs included finally. Almost excellent inter- and intra-observer agreements (all ICC > 0.82) were observed for all three-ROI methods, the volumetric method has the highest values (inter-observer ICC 0.967, intra-observer ICC 0.919, 0.926, respectively). The mean stiffnesses of poorly differentiated HCC obtained by two readers were significantly higher than well-or-moderately differentiated HCC with volumetric method (7.07 ± 1.57 Kpa, 5.00 ± 1.49 Kpa, and 6.85 ± 1.49 Kpa, 4.94 ± 1.48 Kpa, respectively) and three-ROI method (6.14 ± 1.71 Kpa, 4.91 ± 1.56 Kpa and 5.94 ± 1.61 Kpa, 4.84 ± 1.54 Kpa, respectively) but not on single-ROI method (p > 0.005), for the diagnostic performance, the highest area under the curve (AUC) with a value of 0.837, 0.812 by using the volumetric method, followed by the three-ROI method (0.713, 0.754) and single-ROI method.

Conclusion: Different ROI positioning methods significantly affect HCC tumor stiffness measurements. The whole tumor volumetric analysis is superior to ROI-based methods for predicting the grade of HCC.
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http://dx.doi.org/10.1007/s00261-021-03150-4DOI Listing
June 2021

Wearable triboelectric nanogenerators for heart rate monitoring.

Chem Commun (Camb) 2021 Jun 4. Epub 2021 Jun 4.

Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Cardiovascular diseases are currently the leading cause of death globally and are projected to remain the leading cause in 2040, making heart rate an important physiological indicator that should be regularly monitored. Current heart rate monitoring techniques, including photoplethysmography and electrocardiography, are inconvenient for continuous biomonitoring in a wearable way. With a collection of compelling features, such as light weight and high sensitivity, triboelectric nanogenerators (TENGs) have become an emerging and cost-effective biotechnology for long-term and continuous heart rate monitoring in a wearable manner. In this review, we systematically discuss the biomechanics of heart beat, working mechanisms of TENGs, and exemplary applications of TENGs for self-powered heart rate monitoring. Finally, we conclude with a discussion of the potential for technology development in the future.
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http://dx.doi.org/10.1039/d1cc02091aDOI Listing
June 2021

Genome-Wide Analysis of the DUF4228 Family in Soybean and Functional Identification of in Response to Drought and Salt Stresses.

Front Plant Sci 2021 17;12:628299. Epub 2021 May 17.

College of Life Sciences/College of Agronomy, Jilin Agricultural University, Changchun, China.

Domain of unknown function 4228 (DUF4228) proteins are a class of proteins widely found in plants, playing an important role in response to abiotic stresses. However, studies on the DUF4228 family in soybean ( L.) are sparse. In this study, we identified a total of 81 genes in soybean genome, named systematically based on their chromosome distributions. Results showed that these genes were unevenly distributed on the 20 chromosomes of soybean. The predicted soybean DUF4228 proteins were identified in three groups (Groups I-III) based on a maximum likelihood phylogenetic tree. Genetic structure analysis showed that most of the genes contained no introns. Expression profiling showed that genes were widely expressed in different organs and tissues in soybean. RNA-seq data were used to characterize the expression profiles of genes under the treatments of drought and salt stresses, with nine genes showing significant up-regulation under both drought and salt stress further functionally verified by promoter (-acting elements) analysis and quantitative real-time PCR (qRT-PCR). Due to its upregulation under drought and salt stresses based on both RNA-seq and qRT-PCR analyses, was selected for further functional analysis in transgenic plants. Under drought stress, the degree of leaf curling and wilting of the -overexpressing (-OE) line was lower than that of the empty vector (EV) line. -OE lines also showed increased proline content, relative water content (RWC), and chlorophyll content, and decreased contents of malondialdehyde (MDA), HO, and O. Under salt stress, the changes in phenotypic and physiological indicators of transgenic plants were the same as those under drought stress. In addition, overexpression of the gene promoted the expression of marker genes under both drought and salt stresses. Taken together, the results indicated that genes play important roles in response to abiotic stresses in soybean.
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http://dx.doi.org/10.3389/fpls.2021.628299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166234PMC
May 2021

Silencing HIPPI Suppresses Tumor Progression in Non-Small-Cell Lung Cancer by Inhibiting DNA Replication.

Onco Targets Ther 2021 27;14:3467-3480. Epub 2021 May 27.

Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.

Introduction: Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 80%-85% of all cases of lung cancer. Huntingtin interacting protein-1 interacting protein (HIPPI) is a transcription regulator and plays an important role in apoptotic cell death. However, the role of HIPPI in NSCLC remains unclear.

Methods: Immunohistochemistry (IHC) and qRT-PCR were performed for expression analysis. The roles of HIPPI were studied using cell counting kit-8 (CCK-8), colony formation, flow cytometry, wound healing, Transwell invasion assays and mouse xenograft model. Gene microarray analysis and bioinformatics analysis were used to identify differentially expressed genes after HIPPI silencing.

Results: HIPPI is highly expressed in NSCLC tissues relative to adjacent normal tissues. Targeting HIPPI by RNA interference inhibits NSCLC cell proliferation in vitro and tumor growth in vivo. HIPPI silencing also attenuates cell migration and invasion and enhances cisplatin sensitivity in NSCLC cells. Mechanistic investigation suggests that HIPPI can positively regulate the expression of MCM2, MCM6 and MCM8, which are key regulators of DNA replication. Furthermore, consistent with HIPPI, MCM2, MCM6 and MCM8 are also upregulated in NSCLC tissues.

Conclusion: Our study highlights the importance of HIPPI for tumor biology in NSCLC and suggests that HIPPI may be a potential therapeutic target for NSCLC treatment.
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http://dx.doi.org/10.2147/OTT.S305388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166357PMC
May 2021

Circ-PNPT1 contributes to gestational diabetes mellitus (GDM) by regulating the function of trophoblast cells through miR-889-3p/PAK1 axis.

Diabetol Metab Syndr 2021 Jun 1;13(1):58. Epub 2021 Jun 1.

Department of Obsterics, Maternal and Child Health Hospital of Hubei Province, No.745 Wulu Road, Hongshan District, Wuhan City, 430070, Hubei Province, China.

Background: Gestational diabetes mellitus (GDM) is the most common medical complication of pregnancy. CircRNA polyribonucleotide nucleotidyltransferase 1 (circ-PNPT1) has been found to be abnormally expressed in GDM patients. However, function and mechanism of circ-PNPT1 in GDM remain largely undefined.

Methods: Levels of circ-PNPT1, microRNA (miR)-889-3p and PAK1 (p21 (RAC1) activated kinase 1) were detected using quantitative real-time polymerase chain reaction and Western blot assays. Cell viability, apoptosis, migration and invasion were determined using cell counting kit-8 assay, flow cytometry, transwell and wound healing assays, respectively. The binding interaction between miR-889-3p and circ-PNPT1 or PAK1 was verified using dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Exosomes were obtained from culture media by the use of commercial kits and qualified by transmission electron microscopy (TEM).

Results: Circ-PNPT1 was highly expressed in the placental tissues of GDM and high glucose (HG)-induced trophoblast cells. Knockdown of circ-PNPT1 reversed HG-induced arrest of trophoblast cell viability, migration, invasion and the promotion of cell apoptosis. Mechanistically, we confirmed circ-PNPT1 could promote the expression of PAK1, the target of miR-889-3p, by directly sponging miR-889-3p, and circ-PNPT1 regulated HG-induced trophoblast cell dysfunction by miR-889-3p/PAK1 axis. Further studies showed circ-PNPT1 was packaged into exosomes and could be internalized by surrounding trophoblast cells.

Conclusion: Circ-PNPT1 promoted HG-induced trophoblast cell biological dysfunction through miR-889-3p/PAK1 axis. Meanwhile, it could be transferred from HG-induced trophoblast cells to surrounding untreated cells via exosomes.
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http://dx.doi.org/10.1186/s13098-021-00678-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8171017PMC
June 2021

Clinical characteristics and risk factors for poor prognosis among HIV patients with Talaromyces marneffei bloodstream infection.

BMC Infect Dis 2021 Jun 1;21(1):514. Epub 2021 Jun 1.

Department of Infection and Immunity, Shanghai Public Health Clinical Center, Shanghai, China.

Background: Talaromyces marneffei (TM) bloodstream infection is common in Acquired Immunodeficiency Syndrome (AIDS) patients with extreme immunodeficiency in Southeast Asia and South China, however, clinical case study on TM bloodstream infection is scarce. We retrospectively analyzed the clinical characteristics of TM bloodstream infection in hospitalized AIDS patients and determined the outcomes of hospitalization after diagnosis in our hospital over the past 5 years.

Methods: From January 2015 to July 2020, 87 cases of TM detected by blood culture in patients admitted to our center were collected. The admission complaints, blood cells, biochemistry, CD4 and CD8 cell counts and 1,3-β-D-glucan (BDG), procalcitonin (PCT), CRP level on the day of blood culture test, and outcomes during hospitalization were analyzed. Logistic regression analysis was performed for the risk factors for poor prognosis (60 cases). Spearman correlation analysis was used to analyze the correlation between peripheral blood cells, albumin and the time required for TM turnaround in blood culture. The difference was statistically significant when the P value was < 0.05.

Results: A total of 87 patients were collected, with a median age of 34 years, a median hemoglobin of 94 g/L and CD4 count of 7/μl. The rate of TM bloodstream infection among all in-hospital patients increased from 0.99% in 2015 to 2.09% in 2020(half year). Patients with TM bloodstream infection with CD8 count < 200/μl had a 12.6-fold higher risk of poor prognosis than those with CD8 count > 200/μl (p = 0.04), and those with BDG < 100 pg/mL had a 34.9-fold higher risk of poor prognosis than those with BDG > 100 pg/mL (p = 0.01).

Conclusions: TM bloodstream infection is becoming more common in advanced AIDS patients in endemic areas. For those patients with extremely low CD4 and CD8 cell counts below 200/μl is with an increased risk of poor prognosis.
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http://dx.doi.org/10.1186/s12879-021-06232-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170804PMC
June 2021

Comparative Study of Chemical Compositions and Antioxidant Capacities of Oils Obtained from 15 Macadamia () Cultivars in China.

Foods 2021 May 10;10(5). Epub 2021 May 10.

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China.

The planting area of macadamia in China accounted for more than one third of the world's planted area. The lipid compositions, minor components, and antioxidant capacities of fifteen varieties of macadamia oil (MO) in China were comparatively investigated. All varieties of MO were rich in monounsaturated fatty acids, mainly including oleic acid (61.74-66.47%) and palmitoleic acid (13.22-17.63%). The main triacylglycerols of MO were first time reported, including 19.2-26.1% of triolein, 16.4-18.2% of 1-palmitoyl-2,3-dioleoyl-glycerol, and 11.9-13.7% of 1-palmitoleoyl-2-oleoyl-3-stearoyl-glycerol, etc. The polyphenol, α-tocotrienol and squalene content varied among the cultivars, while Fuji (791) contained the highest polyphenols and squalene content. Multiple linear regression analysis indicated the polyphenols and squalene content positively correlated with the antioxidant capacity. This study can provide a crucial directive for the breeding of macadamia and offer an insight into industrial application of MO in China.
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http://dx.doi.org/10.3390/foods10051031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8151099PMC
May 2021

Using MR elastography to assess portal hypertension and response to beta-blockers in patients with cirrhosis.

Liver Int 2021 Jun 1. Epub 2021 Jun 1.

Centre of Gastroenterology, Medical division, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.

Background: MR elastography can determine organ-related stiffness, which reflects the degree of fibrosis. Liver stiffness increases in cirrhosis, and stiffness increases further post-prandially due to increased portal blood in-flow. Non-selective beta-blockers (NSBB) reduce the portal venous inflow, but their effect on liver and spleen stiffness are disputed.

Aims: To assess whether MR elastography of the liver or spleen reflects the severity of cirrhosis, whether treatment with NSBB changes liver and spleen stiffness, and whether changes in stiffness can predict the effect of NSBB on portal pressure.

Methods: Fifty-two patients with cirrhosis underwent liver vein catheterization and two-dimensional (2D) MR elastography on separate days. Thirty-six of the patients had a hepatic venous pressure gradient (HVPG) of ≥12mmHg and were tested prior to, and after, intravenous infusion of NSBB using HVPG measurement and MR elastography.

Results: HVPG showed a strong, positive, linear relationship with liver stiffness (r =0.92; p<0.001) and spleen stiffness (r =0.94; p<0.001). The cut-off points for identifying patients with a HVPG ≥12mmHg was 7.7kPa for liver stiffness (sensitivity 0.78, specificity 0.64) and 10.5kPa for spleen stiffness (sensitivity 0.8, specificity 0.79). Intravenous administration of NSBB significantly decreased spleen stiffness by 6.9% (CI: 3.5;10.4, p<0.001), but NSBB had no consistent effect on liver stiffness. However, changes in spleen stiffness was not related to the HVPG response (p=0.75).

Conclusions: 2D MR elastographic estimation of liver or spleen stiffness reflects the degree of portal hypertension in patients with liver cirrhosis, but changes in stiffness after NSBB do not predict the effect on HVPG.
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http://dx.doi.org/10.1111/liv.14981DOI Listing
June 2021

Regulating Electrocatalytic Oxygen Reduction Activity of Metal Coordination Polymer via d-π Conjugation.

Angew Chem Int Ed Engl 2021 May 29. Epub 2021 May 29.

Nankai University, College of Chemistry, CHINA.

Non-noble transition metal complexes have attracted growing interest as efficient electrocatalysts for oxygen reduction reaction (ORR) while their activities still lack rational and effective regulation. Herein, we propose a d-π conjugation strategy for rough and fine tuning of ORR activity in TM-BTA (TM = Mn/Fe/Co/Ni/Cu, BTA = 1,2,4,5-benzenetetramine) coordination polymers. By first-principle calculations, we elucidate that the strong d-π conjugation elevates the [[EQUATION]] / [[EQUATION]] orbitals of TM centers to enhance intermediate absorption and strengthens the electronic modulation effect from substitute groups on ligands. Based on this strategy, Co-TABQ (tetramino benzoquinone) are found to approach the top of ORR activity volcano. The synthesized Co-TABQ with atomically distributed Co on carbon nanotubes exhibits a half-wave potential of 0.85 V and a specific current of 130 mA mgmetal-1 at 0.8 V, outperforming the benchmark Pt/C. The high activity, low peroxide yield, and considerable durability of Co-BTA and Co-TABQ promise their application in oxygen electrocatalysis. This study provides mechanistic insight into the rational design of transition metal complexes catalysts.
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http://dx.doi.org/10.1002/anie.202104494DOI Listing
May 2021

Correction to: HnRNP F/H associate with hTERC and telomerase holoenzyme to modulate telomerase function and promote cell proliferation.

Cell Death Differ 2021 May 27. Epub 2021 May 27.

Peking University Research Center on Aging, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, Department of Integration of Chinese and Western Medicine, School of Basic Medical Science, Peking University, 100191, Beijing, China.

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http://dx.doi.org/10.1038/s41418-021-00806-yDOI Listing
May 2021

Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy.

Nat Commun 2021 05 27;12(1):3187. Epub 2021 May 27.

Shanghai Pudong Hospital & Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.

Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form "micro-thrombi" with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic ([email protected]) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. [email protected] is found efficiently impeded EMT, inhibited the formation of "micro-thrombi", and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, [email protected] efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.
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http://dx.doi.org/10.1038/s41467-021-23466-5DOI Listing
May 2021