Publications by authors named "Jun Guo"

1,506 Publications

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Early detection of gram-negative bacteria using metagenomic next-generation sequencing in acute respiratory distress syndrome: A case report.

Exp Ther Med 2022 Sep 15;24(3):573. Epub 2022 Jul 15.

Department of Critical Medicine, Union Jiangbei Hospital, Huazhong University of Science and Technology, Wuhan, Hubei 430100, P.R. China.

Metagenomic next-generation sequencing (mNGS) is an effective method that can be used for the identification of early pathogens in patients with suspected severe pneumonia. However, the potential of mNGS for evaluating the prognosis of acute respiratory distress syndrome (ARDS) in patients with severe pneumonia remains unclear. In the present report, hospital-acquired gram-negative bacteria infections were detected in a case using metagenomic next-generation sequencing (mNGS) in a sample of bronchoalveolar fluid. This was obtained from a 58-year-old male patient with traumatic wet lung after a neurosurgery. According to the results, of which the profiles of the resistance genes were detected by mNGS, drugs designed to control infection were adjusted, namely to polymyxin B (500,000 U/12 h), azithromycin (0.5 g/24 h) and ganciclovir (0.25 g/12 h). Following adjusting treatment for 8 days, the symptoms of lung infection and hypoxemia were markedly improved, resulting in the patient being transferred out of the intensive care unit 15 days after treatment. To conclude, observations from the present report suggest that mNGS is a useful method for the early identification of pathogens in patients with pneumonia caused by ARDS. However, further studies are required to identify the complementary role of mNGS in supporting conventional microbiological methods in routine clinical practice.
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http://dx.doi.org/10.3892/etm.2022.11510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353542PMC
September 2022

Quality assessment and relevant clinical impact of randomized controlled trials on chronic prostatitis/chronic pelvic pain syndrome.

BMC Urol 2022 Aug 8;22(1):122. Epub 2022 Aug 8.

Department of Andrology, Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing, 100091, China.

Objective: This study evaluated the quality of randomized controlled trials (RCTs) on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Methods: We searched PubMed, Web of Science, and Embase for RCTs (original articles) on CP/CPPS published from database establishment to 2021. The RCT quality assessment was performed using the Consolidated Standards of Reporting of Trials (CONSORT) statement and the improved Jadad scale.

Results: In total, 77 RCTs were included. According to the evaluation, 26 (33.77%) papers presented the description of the specific random methods, only 6 (7.79%) papers described the allocation concealment methods, and 26 (33.77%) articles referred to the "blind method". Of the RCTs, 34 (44.16%) papers recorded the number of patients who withdrew from the study, and 67 (87.01%) papers reported adverse reactions. However, few reports mentioned the sample size calculation, clinical trial registration, or information about the relevant research programs and funding. In addition, 19 (24.68%) reports had Jadad scale scores of ≥ 4 points, and 58 (75.32%) reports had Jadad scale scores of ≤ 3 points.

Conclusion: To date, the quality of RCT reports on CP/CPPS needs to be further improved, and the results of the RCTs should be accepted and utilized cautiously. It is suggested that researchers should follow the CONSORT statement and the improved Jadad scale to standardize the design and implementation of RCTs to improve the quality of RCTs and provide reliable evidence for the treatment of CP/CPPS.
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http://dx.doi.org/10.1186/s12894-022-01078-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9361679PMC
August 2022

Study on the Interaction Mechanism Between Soybean Protein Isolates and Lemon Flavor: Isomerization and Degradation of Citral.

Front Nutr 2022 21;9:929023. Epub 2022 Jul 21.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, China.

By headspace solid-phase microextraction/gas chromatography-mass spectrometry, the effects of 1% (w/v) alcohol denatured soybean protein isolates (L-SPI), native soybean protein isolates (N-SPI), as well as the thermal denaturation of soybean protein isolates (H-SPI) on low concentration (24 μmol/L) of citral was studied in aqueous. The results shows that the SPI could catalyze citral isomerization and yield methyl heptenone and acetaldehyde by inverse aldol condensation degradation. 3-Hydroxycitronelloal was formed as an intermediate in this reaction. The catalytic efficiency of the L-SPI was higher than that of N-SPI, whereas the catalytic efficiency of H-SPI was the lowest. Additionally, it shows that the catalytic efficiency increased as the pH increased. The catalytic efficiency of 7S (Soybean β-Conglycinin) was greater than that of 11S (Soy bean Proglycinin).
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http://dx.doi.org/10.3389/fnut.2022.929023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355578PMC
July 2022

Mechanosensitive Piezo channels mediate the physiological and pathophysiological changes in the respiratory system.

Respir Res 2022 Jul 29;23(1):196. Epub 2022 Jul 29.

Department of Critical Care Medicine, West China Hospital of Sichuan University, No. 17, Section 3, Renmin South Road, Wuhou District, Chengdu, 610000, Sichuan, China.

Mechanosensitive Piezo ion channels were first reported in 2010 in a mouse neuroblastoma cell line, opening up a new field for studying the composition and function of eukaryotic mechanically activated channels. During the past decade, Piezo ion channels were identified in many species, such as bacteria, Drosophila, and mammals. In mammals, basic life activities, such as the sense of touch, proprioception, hearing, vascular development, and blood pressure regulation, depend on the activation of Piezo ion channels. Cumulative evidence suggests that Piezo ion channels play a major role in lung vascular development and function and diseases like pneumonia, pulmonary hypertension, apnea, and other lung-related diseases. In this review, we focused on studies that reported specific functions of Piezos in tissues and emphasized the physiological and pathological effects of their absence or functional mutations on the respiratory system.
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http://dx.doi.org/10.1186/s12931-022-02122-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9338466PMC
July 2022

Glycine-serine-rich effector PstGSRE4 in Puccinia striiformis f. sp. tritici inhibits the activity of copper zinc superoxide dismutase to modulate immunity in wheat.

PLoS Pathog 2022 Jul 26;18(7):e1010702. Epub 2022 Jul 26.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi, P. R. China.

Puccinia striiformis f. sp. tritici (Pst) secretes an array of specific effector proteins to manipulate host immunity and promote pathogen colonization. In a previous study, we functionally characterized a glycine-serine-rich effector PstGSRE1 with a glycine-serine-rich motif (m9). However, the mechanisms of glycine-serine-rich effectors (GSREs) remain obscure. Here we report a new glycine-serine-rich effector, PstGSRE4, which has no m9-like motif but inhibits the enzyme activity of wheat copper zinc superoxide dismutase TaCZSOD2, which acts as a positive regulator of wheat resistance to Pst. By inhibiting the enzyme activity of TaCZSOD2, PstGSRE4 reduces H2O2 accumulation and HR areas to facilitate Pst infection. These findings provide new insights into the molecular mechanisms of GSREs of rust fungi in regulating plant immunity.
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http://dx.doi.org/10.1371/journal.ppat.1010702DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9321418PMC
July 2022

Glutathione S-Transferase Interactions Enhance Wheat Resistance to Powdery Mildew but Not Wheat Stripe Rust.

Plant Physiol 2022 Jul 25. Epub 2022 Jul 25.

State Key Laboratory of Crop Stress Biology for Arid Areas, College of Plant Protection, Northwest A&F University, Yangling, Shaanxi 712100, China.

Wheat stripe rust and powdery mildew are important worldwide diseases of wheat (Triticum aestivum). The wheat cultivar Xingmin318 (XM318) is resistant to both wheat stripe rust and powdery mildew, which are caused by Puccinia striiformis f. sp. tritici (Pst) and Blumeria graminis f. sp. tritici (Bgt), respectively. To explore the difference between wheat defense response against Pst and Bgt, quantitative proteomic analyses of XM318 inoculated with either Pst or Bgt were performed using tandem mass tags (TMT) technology. A total of 741 proteins were identified as differentially accumulated proteins (DAPs). Bioinformatics analyses indicated that some functional categories, including antioxidant activity and immune system process, exhibited obvious differences between Pst and Bgt infections. Intriguingly, only 42 DAPs responded to both Pst and Bgt infections. Twelve DAPs were randomly selected for RT-qPCR analysis, and the mRNA expression levels of 11 were consistent with their protein expression. Furthermore, gene silencing using the virus-induced gene silencing system indicated that glutathione S-transferase (TaGSTU6) has an important role in resistance to Bgt but not to Pst. TaGSTU6 interacted with the cystathionine beta-synthase (CBS) domain-containing protein (TaCBSX3) in both Pst and Bgt infections. Knockdown of TaCBSX3 expression only reduced wheat resistance to Bgt infection. Overexpression of TaGSTU6 and TaCBSX3 in Arabidopsis (Arabidopsis thaliana) promoted plant resistance to Pseudomonas syringae pv. Tomato DC3000. Our results indicate that TaGSTU6 interaction with TaCBSX3 only confers wheat resistance to Bgt, suggesting that wheat has different response mechanisms to Pst and Bgt stress.
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http://dx.doi.org/10.1093/plphys/kiac326DOI Listing
July 2022

An anatomical feasibility study using CTA reconstruction for modified percutaneous lumbar vertebroplasty.

BMC Musculoskelet Disord 2022 Jul 21;23(1):693. Epub 2022 Jul 21.

Orthopaedics Department, First Affiliated Hospital of Tsinghua University, Beijing, China.

Background: Lumbar vertebroplasty via several different types of extrapedicular approach has been reported with acceptable clinical results yet the anatomical basis for its safety is not fully explored. Injury to the lumbar arteries (LAs) is one of the most important potential complications. However, anatomical research on the course and variability of this structure is lacking. To investigate the anatomical feasibility of percutaneous vertebroplasty for lumbar osteoporotic vertebral compression fractures via a unilateral Extrapedicular approach.

Methods: A total of 300 LAs of 30 patients with non-spinal disorders were retrospectively analyzed by computed tomographic angiography (CTA). The lateral aspect of the vertebral body was divided into 9 zones of approximately equal area. The anatomy and orientation of LAs were analyzed in detail.

Results: LAs were most commonly found in the middle third of the body (zones 4, 5, and 6); the upper 1/3 of the vertebral body had LAs distributed only anteriorly and laterally (zones 1 and 2). No arteries were observed in the postero-superior segment (zone 3). From L1 to L3 an arched pattern predominated. At L4 an inferior oblique pattern (antero-superior to postero-inferior) predominated. Limited CTA visualization at L4 and particularly L5 as well as greater anatomical variation means that there is more uncertainty at these levels.

Conclusion: From L1 to L3, the posterior superior segment (zone 1) of the vertebral body appears to be a safe area with low risk of arterial injury. This has relevance for design of a safe lumbar vertebral extrapedicular approach.
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http://dx.doi.org/10.1186/s12891-022-05586-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306169PMC
July 2022

Evaluation of Clinical Outcomes of Icotinib in Patients With Clinically Diagnosed Advanced Lung Cancer With EGFR-Sensitizing Variants Assessed by Circulating Tumor DNA Testing: A Phase 2 Nonrandomized Clinical Trial.

JAMA Oncol 2022 Jul 21. Epub 2022 Jul 21.

State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Importance: The inability to obtain a pathological diagnosis in a certain proportion of patients with clinically diagnosed advanced lung cancer impedes precision treatment in clinical practice.

Objective: To evaluate the clinical outcome of first-line icotinib in patients with clinically diagnosed advanced lung cancer with unknown pathological status and positive epidermal growth factor receptor (EGFR)-sensitizing variants assessed by circulating tumor DNA (ctDNA).

Design, Setting, And Participants: The Efficiency of Icotinib in Plasma ctDNA EGFR Mutation-Positive Patients Diagnosed With Lung Cancer (CHALLENGE) trial is a prospective, multicentered, open-label, single-arm phase 2 nonrandomized clinical trial conducted between July 1, 2017, and July 31, 2019. Patients with systemic treatment-naive, clinically diagnosed advanced peripheral lung cancer, unknown pathological status, and positive pretreatment plasma EGFR-sensitizing variants were eligible. A total of 391 potentially eligible Chinese patients from 19 centers in China were screened for ctDNA EGFR variants by 3 independent detection platforms (Super amplification refractory mutation system [SuperARMS] polymerase chain reaction, droplet digital polymerase chain reaction, and next-generation sequencing), and those with EGFR variants tested by any platform were included. Analyses were conducted from September 9 to December 31, 2021.

Interventions: Enrolled patients were treated with oral icotinib tablets (125 mg 3 times daily) until disease progression, death, or treatment discontinuation due to various reasons, such as toxic effects and withdrawing consent.

Main Outcomes And Measures: The primary end point was objective response rate (ORR). The secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and the concordance among the 3 detection platforms.

Results: Of 116 included patients, 76 (65.5%) were female, and the median (range) age was 64 (37-85) years. The median (IQR) follow-up duration was 36.3 (30.2-40.7) months. The ORR was 52.6% (95% CI, 43.1%-61.9%). The median PFS and OS were 10.3 months (95% CI, 8.3-12.2) and 23.2 months (95% CI, 17.7-28.0), respectively, and the DCR was 84.5% (95% CI, 76.6%-90.5%). The concordance rate among the 3 detection platforms was 80.1% (313 of 391), and the clinical outcomes in patients identified as positive by any platform were comparable.

Conclusions And Relevance: This prospective phase 2 nonrandomized clinical trial suggests that for patients with clinically diagnosed advanced lung cancer with unknown pathological status, ctDNA-based EGFR genotyping could help decision-making in particular clinical situations, while still warranting future larger-scaled real-world exploration.

Trial Registration: ClinicalTrials.gov Identifier: NCT03346811.
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http://dx.doi.org/10.1001/jamaoncol.2022.2719DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9305594PMC
July 2022

Whole-Exome Sequencing Uncovers Specific Genetic Variation Difference Based on Different Modes of Drug Resistance in Small Cell Lung Cancer.

Front Oncol 2022 30;12:891938. Epub 2022 Jun 30.

Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.

The poor survival rate of small cell lung cancer (SCLC) is mainly related to the condition that patients with SCLC often have good responses to first-line chemotherapy initially, but later on, most of these patients relapse rapidly due to resistance to further treatment. In this study, we attempted to analyze whole-exome sequencing data based on the largest sample size to date, to develop a classifier to predict whether a patient will be chemorefractory or chemosensitive and to explicate the risk of recurrence that affects the prognosis of patients. We showed the different characteristics of somatic mutational signatures, somatic mutation genes, and distinct genome instability between chemorefractory and chemosensitive SCLC patients. Amplified mutations in the chemosensitive group inhibited the regulation of the cell cycle process, transcription factor binding, and B-cell differentiation. Analysis of deletion mutation also suggested that detection of the chromosomal-level variation might influence our treatment decisions. Higher PD-L1 expressions (based on TPS methods) were mostly present among chemosensitive patients ( = 0.026), while there were no differences in PD-L1 expressions (based on CPS methods) and CD8 TILs between the two groups. According to the model determined by logistic regression, each sample was endowed with a predictive probability value (PV). The samples were divided into a high-risk group (>0.55) and a low-risk group (≤0.55), and the survival analysis showed obvious differences between the two groups. This study provides a reference basis to translate this knowledge into practice, such as formulating personalized treatment plans, which may benefit Chinese patients with SCLC.
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http://dx.doi.org/10.3389/fonc.2022.891938DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280676PMC
June 2022

Proliferation Marker Ki67 as a Stratification Index of Adjuvant Chemotherapy for Resectable Mucosal Melanoma.

Front Oncol 2022 30;12:895672. Epub 2022 Jun 30.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education, Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital and Institute, Beijing, China.

Background: Adjuvant chemotherapy has been shown to produce a favorable prognosis for patients with resectable mucosal melanoma (MM), resulting in the need for stratification to optimally select patients to benefit from adjuvant therapy. This study analyzed Ki67 as a potential stratification index for adjuvant chemotherapy in resectable MM.

Methods: Patients with resected MM who received subsequent adjuvant therapy in Beijing Cancer Hospital between 2010 and 2018 were retrospectively enrolled and analyzed. Relapse-free survival (RFS) and melanoma-specific survival (MSS) curves were used to perform the survival comparisons across different subgroups.

Results: From Jan 2010 to Dec 2018, 1106 MM patients were screened from a database of 4706 patients and 175 of these patients were finally enrolled. A total of 100 patients received temozolomide (TMZ)-based adjuvant chemotherapy and 75 patients received high-dose interferon-α2b (HDI) adjuvant therapy. Compared with HDI, patients who received TMZ-based adjuvant chemotherapy had significantly superior RFS (21.0 vs. 9.6 months, P = 0.002). For patients with low Ki67 expression (<30%), the two regimens showed no significant difference for impact on RFS (33.9 vs. 22.7 months, P = 0.329). However, for patients with high Ki67 expression (≥30%), TMZ-based adjuvant chemotherapy achieved favorable RFS compared with HDI (18.0 vs. 6.7 months, P < 0.001) and tended to improve MSS compared to HDI (41.4 vs. 25.1 months, P = 0.067).

Conclusion: Compared with HDI, adjuvant chemotherapy may be more relevant for patients with Ki67 ≥ 30%. Ki67 may serve as a potential index to distinguish populations benefiting from adjuvant chemotherapy in resectable MM, and may provide a basis for stratification in the selection of adjuvant regimens.
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http://dx.doi.org/10.3389/fonc.2022.895672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9280123PMC
June 2022

PCSK9 Modulates Macrophage Polarization-Mediated Ventricular Remodeling after Myocardial Infarction.

J Immunol Res 2022 4;2022:7685796. Epub 2022 Jul 4.

Department of Cardiology, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China.

Background And Aims: An increasing number of high-risk patients with coronary heart disease (similar to acute myocardial infarction (AMI)) are using PCSK9 inhibitors. However, whether PCSK9 affects myocardial repair and the molecular mechanism of PCSK9 modulation of immune inflammation after AMI are not known. The present research investigated the role of PCSK9 in the immunomodulation of macrophages after AMI and provided evidence for the clinical application of PCSK9 inhibitors after AMI to improve cardiac repair.

Methods And Results: Wild-type C57BL6/J (WT) and PCSK9 mouse hearts were subjected to left anterior descending (LAD) coronary artery occlusion to establish an AMI model. Correlation analysis showed that higher PCSK9 expression indicated worse cardiac function after AMI, and PCSK9 knockout reduced infarct size, improved cardiac function, and attenuated inflammatory cell infiltration compared to WT mice. Notably, the curative effects of PCSK9 inhibition were abolished after the systemic depletion of macrophages using clodronate liposomes. PCSK9 showed a regulatory effect on macrophage polarization in vivo and in vitro. Our studies also revealed that activation of the TLR4/MyD88/NF-B axis was a possible mechanism of PCSK9 regulation of macrophage polarization.

Conclusion: Our data suggested that PCSK9 modulated macrophage polarization-mediated ventricular remodeling after myocardial infarction.
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http://dx.doi.org/10.1155/2022/7685796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273409PMC
July 2022

Effects of probiotic administration on the digestibility characteristics and growth performance of finishing beef cattle fed a total mixed ration containing different levels of corn stover.

Anim Sci J 2022 Jan;93(1):e13751

College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Heilongjiang Provincial Key Laboratory of Efficient Utilization of Feed Resources and Nutrition Manipulation in Cold Region, Daqing, China.

In this study, we aimed to assess the effects of probiotic administration on the digestibility characteristics and growth performance of finishing beef cattle fed a total mixed ration (TMR) containing different levels of corn stover. One hundred and sixty Simmental × Continental crossbred bulls were randomly allocated to two animal houses (80 bulls each) and randomly assigned four TMR differing in the level of corn stover-high (HCT) and low (LCT)-with or without probiotics in each animal house. Feeding HCT supplemented with probiotics increased (P < 0.05) the apparent digestibility of crude protein (CP), ether extract (EE), neutral detergent fiber (NDF), and acid detergent fiber (ADF). Regardless of probiotic supplementation, the nitrogen intake and fecal nitrogen levels of animals fed HCT were lower than those fed LCT (P < 0.05). Additionally, feeding probiotics increased (P < 0.05) the efficiency of ruminal fermentation, final body weight, and average daily gain (ADG) of animals, with this effect being stronger in animals fed HCT. In conclusion, supplementing probiotics with HCT has a positive effect on the growth of finishing beef cattle, thereby providing economic benefits.
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http://dx.doi.org/10.1111/asj.13751DOI Listing
January 2022

Protein nanoparticle-induced osmotic pressure gradients modify pulmonary edema through hyperpermeability in acute respiratory distress syndrome.

J Nanobiotechnology 2022 Jul 6;20(1):314. Epub 2022 Jul 6.

School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, Jiangsu, People's Republic of China.

Acute respiratory distress syndrome (ARDS), caused by noncardiogenic pulmonary edema (PE), contributes significantly to Coronavirus 2019 (COVID-19)-associated morbidity and mortality. We explored the effect of transmembrane osmotic pressure (OP) gradients in PE using a fluorescence resonance energy transfer-based Intermediate filament (IF) tension optical probe. Angiotensin-II- and bradykinin-induced increases in intracellular protein nanoparticle (PN)-OP were associated with inflammasome production and cytoskeletal depolymerization. Intracellular protein nanoparticle production also resulted in cytomembrane hyperpolarization and L-VGCC-induced calcium signals, which differed from diacylglycerol-induced calcium increment via TRPC6 activation. Both pathways involve voltage-dependent cation influx and OP upregulation via SUR1-TRPM4 channels. Meanwhile, intra/extracellular PN-induced OP gradients across membranes upregulated pulmonary endothelial and alveolar barrier permeability. Attenuation of intracellular PN, calcium signals, and cation influx by drug combinations effectively relieved intracellular OP and pulmonary endothelial nonselective permeability, and improved epithelial fluid absorption and PE. Thus, PN-OP is pivotal in pulmonary edema in ARDS and COVID-19, and transmembrane OP recovery could be used to treat pulmonary edema and develop new drug targets in pulmonary injury.
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http://dx.doi.org/10.1186/s12951-022-01519-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257569PMC
July 2022

Ginsenoside Rg1 ameliorates sepsis-induced acute kidney injury by inhibiting ferroptosis in renal tubular epithelial cells.

J Leukoc Biol 2022 Jun 30. Epub 2022 Jun 30.

Department of Critical Care Medicine, Union Jiangbei Hospital, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Acute kidney injury (AKI) represents a prevailing complication of sepsis, and its onset involves ferroptosis. Ginsenoside Rg1 exerts a positive effect on kidney diseases. This study explored the action of ginsenoside Rg1 in sepsis-induced AKI (SI-AKI) by regulating ferroptosis in renal tubular epithelial cells (TECs). Sepsis rat models were established using cecal ligation and puncture (CLP) and cell models were established by treating human renal TECs (HK-2) with LPS to induce ferroptosis. Serum creatinine (SCr) and blood urea nitrogen (BUN) and urine KIM1 contents in rats were determined by ELISA kits. Kidney tissues were subjected to immunohistochemical and H&E stainings. Iron concentration, malondialdehyde (MDA), glutathione (GSH), and ferroptosis-related protein (ferritin light chain [FTL], ferritin heavy chain [FTH], GSH peroxidase 4 [GPX4], and Ferroptosis suppressor protein 1 [FSP1]) levels in kidney tissues and HK-2 cells were measured using ELISA kits and Western blotting. HK-2 cell viability was detected by cell counting kit-8, and cell death was observed via propidium iodide staining. Reactive oxygen species accumulation in cells was detected using C11 BODIPY 581/591 as a molecular probe. In CLP rats, ginsenoside Rg1 reduced SCr, BUN, KIM1, and NGAL levels, thus palliating SI-AKI. Additionally, ginsenoside Rg1 decreased iron content, FTL, FTH, and MDA levels, and elevated GPX4, FSP1, and GSH levels, thereby inhibiting lipid peroxidation and ferroptosis. Moreover, FSP1 knockdown annulled the inhibition of ginsenoside Rg1 on ferroptosis. In vitro experiments, ginsenoside Rg1 raised HK-2 cell viability and lowered iron accumulation and lipid peroxidation during ferroptosis, and its antiferroptosis activity was dependent on FSP1. Ginsenoside Rg1 alleviates SI-AKI, possibly resulting from inhibition of ferroptosis in renal TECs through FSP1.
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http://dx.doi.org/10.1002/JLB.1A0422-211RDOI Listing
June 2022

Clinicopathological characteristics and prognosis of metastatic collecting duct carcinoma.

Urol Oncol 2022 Aug 27;40(8):385.e1-385.e8. Epub 2022 Jun 27.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Genitourinary Oncology, Peking University Cancer Hospital & Institute, Beijing, China. Electronic address:

Objective: To investigate the clinicopathological characteristics, response to different treatment regimens, and prognostic factors of metastatic collecting duct carcinoma (CDC).

Patients And Methods: Information of patients with metastatic CDC was retrieved from a database including clinical and survival data. Survival outcomes were analyzed with the Kaplan-Meier method, and prognostic factors were identified with the Cox proportional hazard model.

Results: Fifty patients with metastatic CDC were included in this study. Most patients had an advanced T stage (58% T3-4) and high WHO/ISUP grade (86% G3-4). Twenty-nine patients (58%) developed metastases from an early stage, 42% had distant metastases at diagnosis, and 28% received cytoreductive nephrectomy. In the first-line setting, the objective response rate was 27.0%, and the median progression-free survival was 6.4 months (95%CI 4.9-7.9) for 37 patients who received chemotherapy combined with sorafenib. One PR was seen in 4 patients who received anti-PD-1 antibody plus axitinib. The median overall survival for the whole population was 12.6 months (95%CI 7.8-17.4). In univariate analyses, advanced T stage, East Cooperative Oncology Group Performance Score ≥1, anemia, elevated lactate dehydrogenase, and no response to first-line treatment was associated with poor prognosis (P < 0.05). In multivariate analyses, advanced T stage and anemia were independently associated with a poorer prognosis. The Memorial Sloan-Kettering Cancer Center (MSKCC) model (P = 0.002) predicted the prognosis of metastatic CDC patients more accurately than the International Metastatic Renal-Cell Carcinoma Database Consortium (IMDC) model (P = 0.063).

Conclusion: T Stage and anemia were independent prognostic factors for metastatic CDC. MSKCC was more accurate than the IMDC model to predict the outcome. Chemotherapy plus sorafenib demonstrated substantial efficacy in the first-line setting. Anti-PD-1 plus axitinib showed a preliminary antitumor effect and is worthy of further exploration.
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http://dx.doi.org/10.1016/j.urolonc.2022.05.014DOI Listing
August 2022

Sequence-Dependent Tyrosine-Containing Peptide Nanoassemblies for Sensing Tyrosinase and Melanoma.

ACS Macro Lett 2022 07 28;11(7):875-881. Epub 2022 Jun 28.

Quantum Biophotonic Lab, Key Laboratory of Optical Technology and Instrument for Medicine, Ministry of Education, School of Optical-Electrical and Computer-Engineering, University of Shanghai for Science and Technology, Shanghai 200093, China.

Tyrosine-containing peptide nanoassemblies have received tremendous attention because of their potential applications in biomedicine and nanomaterial fields. However, a current outstanding challenge is to direct the equilibrium between oxidative polymerization of precursors and the noncovalent assembly to precisely tune their specific nanostructures and functionalities through the rational design of peptide sequences. With a simple library of tripeptides containing tyrosine, glycine, and lysine, here we demonstrate how amino acid sequence encodes the property of tripeptide nanoassemblies by modulating the enzymatic oxidation of tyrosinase with the accompanied self-assembly, and thus select the pathways toward fluorescent or melanin-like nanoassemblies. The fluorescence of tripeptide nanoassemblies has been demonstrated in sensing both tyrosinase and melanoma. Our findings will provide inspiration of peptide sequence design for generating the complex bioactive peptide nanomaterials for biomedical applications.
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http://dx.doi.org/10.1021/acsmacrolett.2c00180DOI Listing
July 2022

Molecular characterization of a novel virga-like virus associated with wheat.

Arch Virol 2022 Sep 25;167(9):1909-1913. Epub 2022 Jun 25.

State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agroproducts, Key Laboratory of Biotechnology in Plant Protection of MOA of China and Institute of Plant Virology, Ningbo University, Ningbo, 315211, China.

In this work, we report the detection of a novel single-strand RNA virus from wheat, tentatively named "Triticum aestivum-associated virga-like virus 1" (TaAVLV1). Further characterization revealed that the complete genome of TaAVLV1 is divided into two segments, RNA1 and RNA2, which are 3530 and 3466 nt in length, excluding their respective polyA tails, and each contains only one open reading frame (ORF). The ORF of RNA1 encodes an RNA-dependent RNA polymerase (RdRp), while the ORF of RNA2 encodes a putative protein with methyltransferase and helicase domains. Phylogenetic analysis showed that the RdRp of TaAVLV1 is closely related to those of members of the unclassified virga-like virus group in the family Virgaviridae. Thus, we have identified TaAVLV1 as a putative novel virga-like virus belonging to the family Virgaviridae.
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http://dx.doi.org/10.1007/s00705-022-05473-zDOI Listing
September 2022

Adjuvant-Protein Conjugate Vaccine with Built-In TLR7 Agonist on S1 Induces Potent Immunity against SARS-CoV-2 and Variants of Concern.

ACS Infect Dis 2022 Jul 24;8(7):1367-1375. Epub 2022 Jun 24.

Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, International Joint Research Center for Intelligent Biosensing Technology and Health, Hubei International Scientific and Technological Cooperation Base of Pesticide and Green Synthesis, College of Chemistry, Central China Normal University, Wuhan 430079, China.

With the global pandemic of the new coronavirus disease (COVID-19), a safe, effective, and affordable mass-produced vaccine remains the current focus of research. Herein, we designed an adjuvant-protein conjugate vaccine candidate, in which the TLR7 agonist (TLR7a) was conjugated to S1 subunit of SARS-CoV-2 spike protein, and systematically compared the effect of different numbers of built-in TLR7a on the immune activity for the first time. As the number of built-in TLR7a increased, a bell-shaped reaction was observed in three TLR7a-S1 conjugates, with TLR7a(10)-S1 (with around 10 built-in adjuvant molecules on one S1 protein) eliciting a more potent immune response than TLR7a(2)-S1 and TLR7a(18)-S1. This adjuvant-protein conjugate strategy allows the built-in adjuvant to provide cluster effects and prevents systemic toxicity and facilitates the co-delivery of adjuvant and antigen. Vaccination of mice with TLR7a(10)-S1 triggered a potent humoral and cellular immunity and a balanced Th1/Th2 immune response. Meanwhile, the vaccine induces effective neutralizing antibodies against SARS-CoV-2 and all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). It is expected that the adjuvant-protein conjugate strategy has great potential to construct a potent recombinant protein vaccine candidate against various types of diseases.
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http://dx.doi.org/10.1021/acsinfecdis.2c00259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260725PMC
July 2022

A piecewise sine waveguide for terahertz traveling wave tube.

Sci Rep 2022 Jun 21;12(1):10449. Epub 2022 Jun 21.

School of Electronic Science and Engineering, University of Electronic Science and Technology University of China, Chengdu, 610054, China.

In this paper, a piecewise sine waveguide (PWSWG) is proposed as the slow-wave structure (SWS) to develop high-power terahertz (THz) traveling wave tubes (TWTs). The PWSWG is an improvement over the rectangular waveguide wherein its two E-planes simultaneously oscillate up and down along the longitudinal direction. The oscillation curve in the H-plane is a piecewise sine curve formed by inserting line segments into the peaks and troughs of the sine curve. The simulation analysis and experimental verification show that the PWSWG offers the advantages of large interaction impedance and excellent electromagnetic transmission performance. Furthermore, the calculation results of beam-wave interaction show that the TWT based on PWSWG SWS can generate a radiated power of 253.1 W at the typical frequency of 220 GHz, corresponding to a gain of 37.04 dB and an interaction efficiency of 6.92%. Compared with the conventional SWG TWTs, the PWSWG TWT has higher interaction efficiency and shorter saturation tube length. In conclusion, the PWSWG proposed in this paper can be considered a suitable SWS for high-power THz radiation sources.
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http://dx.doi.org/10.1038/s41598-022-14587-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213447PMC
June 2022

A novel maladaptive unfolded protein response as a mechanism for small bowel resection-induced liver injury.

Am J Physiol Gastrointest Liver Physiol 2022 Sep 21;323(3):G165-G176. Epub 2022 Jun 21.

Division of Pediatric Surgery, Department of Surgery, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri.

The unfolded protein response (UPR) is a complex adaptive signaling pathway activated by the accumulation of misfolded proteins in the endoplasmic reticulum (ER). ER stress (ERS) triggers a cascade of responses that converge upon C/EBP homologous protein (CHOP) to drive inflammation and apoptosis. Herein, we sought to determine whether liver injury and fibrosis after small bowel resection (SBR) were mediated by a maladaptive hepatic ERS/UPR. C57BL/6 mice underwent 50% proximal SBR or sham operation. Markers of liver injury and UPR/ERS pathways were analyzed. These were compared with experimental groups including dietary fat manipulation, tauroursodeoxycholic acid (TUDCA) treatment, distal SBR, and global CHOP knockout (KO). At 10 wk, proximal SBR had elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST) ( < 0.005) and greater hepatic tumor necrosis factor-α (TNFα) ( = 0.001) and collagen type 1 α1 (COL1A1) ( = 0.02) than shams. SBR livers had increased CHOP and p-eIF2α, but were absent in activating transcription factor 4 (ATF4) protein expression. Low-fat diet (LFD), TUDCA, and distal SBR groups had decreased liver enzymes, inflammation, and fibrosis ( < 0.05). Importantly, they demonstrated reversal of hepatic UPR with diminished CHOP and robust ATF4 signal. CHOP KO-SBR had decreased ALT but not AST compared with wild-type (WT)-SBR ( = 0.01, = 0.12). There were no differences in TNFα and COL1A1 ( = 0.09, = 0.50). SBR-induced liver injury, fibrosis is associated with a novel hepatic UPR/ERS response characterized by increased CHOP and decreased ATF4. LFD, TUDCA, and ileocecal resection rescued the hepatic phenotype and reversed the UPR pattern. Global CHOP KO only partially attenuated liver injury. This underscores the significance of disruptions to the gut/liver axis after SBR and potentiates targets to mitigate the progression of intestinal failure-associated liver disease. The unfolded protein response (UPR) is a complex signaling cascade that converges upon C/EBP-homologous protein (CHOP). Under conditions of chronic cellular stress, the UPR shifts from homeostatic to proapoptotic leading to inflammation and cell death. Here, we provide evidence that small bowel resection-induced liver injury and fibrosis are mediated by a maladaptive hepatic UPR. Low-fat diet, TUDCA treatment, and ileocecal resection rescued the hepatic phenotype and reversed the UPR pattern.
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http://dx.doi.org/10.1152/ajpgi.00302.2021DOI Listing
September 2022

Analysis of risk factors associated with breast cancer in women: a systematic review and meta-analysis.

Transl Cancer Res 2022 May;11(5):1344-1353

Department of Nursing, Shanxi Bethune Hospital, Taiyuan, China.

Background: The aim of the present study was to explore the risk factors and protective factors related to breast cancer onset in women, but there is still a big debate in this respect. Therefore, it is necessary to systematically review the risk factors induced by breast cancer by using meta methods to guide clinical prevention and treatment.

Methods: Studies on factors related to breast cancer onset in Chinese women were retrieved from articles from Chinese, international databases published and organizations and websites, and registers from January 2014 to January 2021. Articles were independently screened, extracted, and evaluated for quality by 2 researchers. The Cochrane Collaboration Center provided Review Manger 5.2 software [Cochrane Information Management System (IMS)] for statistical analysis, and the risk ratio of dichotic variables was adopted.

Results: History of benign breast disease [odds ratio (OR) 1.03, 95% confidence interval (CI): 0.95-1.12, P=0.42], family history of breast cancer (OR: 2.02, 95% CI: 1.83-2.23, P<0.00001), menopause onset >50 years of age (OR: 1.78, 95% CI: 1.62-1.95, P<0.00001), and use of oral contraceptives (OR: 1.16, 95% CI: 1.02-1.32, P=0.02) were found to be breast cancer risk factors. The number of term pregnancies (OR: 0.80, 95% CI: 0.66-0.97, P=0.03) and breastfeeding (OR: 0.84, 95% CI: 0.74-0.96, P=0.01) were found to be protective factors for breast cancer.

Conclusions: In order to control the occurrence of breast cancer, effective measures should be taken to effectively avoid related risk factors, and breastfeeding and high-risk population screening should be advocated.
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http://dx.doi.org/10.21037/tcr-22-193DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189186PMC
May 2022

Oriented preparation of Large-Area uniform CsTeI perovskite film for high performance X-ray detector.

J Colloid Interface Sci 2022 Oct 3;624:629-636. Epub 2022 Jun 3.

State Key Laboratory of Solidification Processing, Key Laboratory of Radiation Detection Materials and Devices, and School of Materials Science and Engineering, Northwestern Polytechnical University, Xi'an 710072, China. Electronic address:

Large-area flexible perovskite films are attracting widespread research interest for applications in wearable solar cells, portable photodetectors, bendable X-ray imaging detectors and other implantable optoelectronic devices. In this work, a facile mobile platform assisted electrospray method is developed to prepare large-area (100 cm) lead-free CsTeI film on flexible polyimide substrate. The spraying parameters are coupled with the growth temperature to achieve a dynamic balance. The as-prepared film by optimized process shows high uniformity in grain size, thickness and X-ray response without pinholes and cracks. Moreover, oriented nucleation is more likely to occur on the flexible organic substrates for less growth stress and mismatch stress, leading to preferred (222) plane orientation. X-ray detectors prepared with the films exhibit a resistivity of 1.9 × 10 Ω·cm, an X-ray sensitivity of 226.8 μC⋅Gy⋅cm and a transient response rise time as fast as 42 ms under 50 kV X-ray at an electrical field of 6.67 × 10 V·mm. The modified electrospray method shows great potential applications for large-area devices of radiography, solar cell and other optoelectronic devices.
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http://dx.doi.org/10.1016/j.jcis.2022.06.003DOI Listing
October 2022

Delayed Onset Heparin-Induced Thrombocytopenia Presenting as Fever of Unknown Origin.

Am J Med 2022 Jun 6. Epub 2022 Jun 6.

Department of Internal Medicine, University of Florida College of Medicine, Jacksonville.

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http://dx.doi.org/10.1016/j.amjmed.2022.05.019DOI Listing
June 2022

Steroid profile in dried blood spots by liquid chromatography tandem mass spectrometry: Application to newborn screening for congenital adrenal hyperplasia in China.

Steroids 2022 Sep 31;185:109056. Epub 2022 May 31.

Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, China. Electronic address:

Background: Newborn screening for congenital adrenal hyperplasia (CAH) using 17-hydroxyprogesterone dissociation-enhanced, lanthanide fluorescence immunoassay (DELFIA) generates a large number of false-positive results. The present study aimed to improve the sensitivity of the CAH neonatal screening by including second-tier steroid profiling in dried blood spots (DBS) using liquid chromatography tandem mass spectrometry (LC-MS/MS).

Methods: We developed and validated a LC-MS/MS method for simultaneous determination of six steroids in DBS, including androstenedione, testosterone, 17-hydroxyprogesterone, 11-deoxycortisol, 21-deoxycortisol, and cortisol. Two 5-mm blood spots were eluted by internal standard working solution. We analyzed 1170 DBS samples from neonates to determine gestational age-specific reference intervals. In order to test the specificity of the second-tier method, we analyzed 707 cards with a positive screening by DELFIA.

Results: Values of intra- and inter-day precision coefficients of variance and accuracy were 2.0%-13.3% and 85.8%-114.5%, respectively. Recovery ranged from 85.0% to 106.9%. The lower limit of quantification was 0.5 ng/mL for 21-deoxycortisol, 0.25 ng/mL for 17-hydroxyprogesterone and cortisol, and 0.1 ng/mL for testosterone, androstenedione, and 11-deoxycortisol. In addition, the linearity range was 0.25-50 ng/mL (R > 0.99). According to the 17-hydroxyprogesterone levels and ratios of (androstenedione + 17-hydroxyprogesterone)/cortisol in the 707 positive screening samples, 77 neonates should receive recall visit. The number of false-positive results reduced by 89.1%. Totally, 18 newborns were diagnosed with 21-hydroxylase deficiency, one with P450 oxidoreductase deficiency and one with 11β-hydroxylase deficiency. With two-tier screening, the positive predictive value increased to 26.0%.

Conclusions: The second-tier steroid profiling by LC-MS/MS reduced the false-positive rate and improved the positive predictive value of CAH screening. We suggest applying this steroid profiling assay as a second-tier test for CAH screening in China.
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http://dx.doi.org/10.1016/j.steroids.2022.109056DOI Listing
September 2022

Extracts Attenuate CFA-Induced Inflammatory Pain via TRPV1 in Mice.

Evid Based Complement Alternat Med 2022 23;2022:4684830. Epub 2022 May 23.

School of Medicine, Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China.

, belonging to the family Apiaceae, is a well-known herbal medicine. The roots of are commonly used for the treatment of headache, toothache, abscess, furunculosis, and acne. However, little is known about their analgesic molecular mechanism underlying pain relief. In this study, we used behavioral tests to assess the analgesic effect of the ADE ( extracts) on CFA (complete Freund's adjuvant)-induced inflammatory pain mice models. TRPV1 (Transient Receptor Potential Cation Channel Subfamily Member 1) protein activity in dorsal root ganglion (DRG) was assessed with a calcium imaging assay. TRPV1 expression was detected with western blot and immunohistochemistry. Then, we examined the constituents of ADE using combined ultra-performance liquid chromatography-quadrupole time-of-light mass spectrometry (UPLC/Q-TOF-MS). Our results showed that ADE effectively attenuated mechanical and thermal hypersensitivities in CFA-induced inflammatory pain model in mice. ADE also significantly reduced the activity and the protein expression of TRPV1 in DRG from CFA mice. Therefore, ADE might be an attractive and suitable analgesic agent for the management of chronic inflammatory pain.
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http://dx.doi.org/10.1155/2022/4684830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9152374PMC
May 2022

Enabling dual valorization of lignocellulose by fluorescent lignin carbon dots and biochar-supported persulfate activation: Towards waste-treats-pollutant.

J Hazard Mater 2022 08 4;435:129072. Epub 2022 May 4.

Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.

The rationally-designed lignocellulose valorization that promotes a novel "waste-treats-pollutant" standpoint is highly desired yet still challenging for the spread of biomass industry. At this point, a cascade technique with the assistance of deep eutectic solvent (DES) fractionation is tailored to dually valorize wheat straw into fluorescent lignin carbon dots (LCDs) and bimetallic Mg-Fe oxide-decorated biochar (MBC) via solvothermal engineering and co-precipitation/pyrolysis respectively. Benefitting from the abundance of β-aryl ether and hydroxyl groups in DES-extracted lignin, the photoluminescence LCDs emit blue color in a wide excitation span, which can be adopted to selectively detect ferric ions (Fe) in a broad dosage scale with a highly linear correlation of 10-50 μM. Taking advantages of the MBC-aided persulfate activation, we propose the efficient arbidol removal system with a universal concentration of 20-200 ppm in the scalable pH ranging from 3 to 11. The dominate migration pathways involving with active oxygen species and surface electron transfer are comprehensively studied via electron paramagnetic resonance, radical-quenching experiments, and theoretical arithmetic. With the endeavor of biorefineries, this full-scale platform ignites the dazzling wildfire from dual lignocellulose valorization that will also seek its accurate position in the kingdoms of functional materials and wastewater restoration.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129072DOI Listing
August 2022

Exosomal circRNA BTG2 derived from RBP-J overexpressed-macrophages inhibits glioma progression via miR-25-3p/PTEN.

Cell Death Dis 2022 May 28;13(5):506. Epub 2022 May 28.

Department of Neurosurgery, The Yancheng Clinical College of Xuzhou Medical University, The First people's Hospital of Yancheng, Yancheng, P. R. China.

Macrophage-derived exosomes (Mφ-Exos) are involved in tumor progression, but its role in glioma is not fully understood. RBP-J is related to macrophage activation. In this study, we assess the role of exosomes derived from RBP-J-overexpressed macrophages (RBP-J OE Mφ-Exos) in glioma. The circular RNA (circRNA) profiles in RBP-J OE Mφ-Exos and THP-1-like macrophages (WT Mφ)-Exos were evaluated using circRNA microarray. Then the functions of Mφ-Exo-circRNA in glioma cells were assessed via CCK-8, EdU, Transwell invasion, and nude mouse assays. Besides, luciferase reporter assay, RNA immunoprecipitation, and Pearson's correlation analysis were adopted to confirm interactions. We found that circRNA BTG (circBTG2) is upregulated in RBP-J OE Mφ-Exos compared to WT Mφ-Exos. RBP-J OE Mφ-Exos co-culture and circBTG2 overexpression inhibited proliferation and invasion of glioma cells, whereas circBTG2 knockdown promotes tumor growth in vivo. The effects of RBP-J OE Mφ-Exos on glioma cells can be reversed by the circBTG2 knockdown. In conclusions, Exo-circBTG2 secreted from RBP-J OE Mφ inhibits tumor progression through the circBTG2/miR-25-3p/PTEN pathway, and circBTG2 is probably a diagnostic biomarker and potential target for glioma therapy.
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http://dx.doi.org/10.1038/s41419-022-04908-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148311PMC
May 2022

Gestational exposure to fluoride impairs cognition in C57 BL/6 J male offspring mice via the p-Creb1-BDNF-TrkB signaling pathway.

Ecotoxicol Environ Saf 2022 Jul 25;239:113682. Epub 2022 May 25.

Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China. Electronic address:

Fluoride exposure has a detrimental effect on neurodevelopment, while the underlying processes remain unknown. The goal of this study was to investigate how fluoride impacts synaptogenesis, with a focus on the phosphorylation of Creb1 (p-Creb1)-brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) pathway. We generated a sodium fluoride (NaF) model using C57 BL/6 J mice exposed to 100 mg/L NaF from gestation day 1 (GD1) to GD20. It was identified that NaF treatment impaired the learning and memory abilities of the male offspring, reduced dendritic spine density, lowered postsynaptic density protein-95 (PSD95) and synaptophysin (SYN) expression in the male offspring's hippocampus, indicating that synaptic dysfunction may contribute to the cognitive impairment in the NaF model. In addition, in vivo experiment demonstrated that the protein abundance of BDNF and the ratio of p-Creb1 to Creb1 were increased in the hippocampus of NaF offspring, while the level of TrkB was reduced. Similarly, PC12 cells treated with NaF also showed increased expression of BDNF and decreased levels of TrkB. Notably, fluoride treatment increased p-Creb1 in vitro, while inhibiting p-Creb1 by 66615 significantly alleviated the effects of NaF exposure, indicating that p-Creb1 exerts a regulatory function in the BDNF-TrkB pathway. Altogether, these results demonstrated prenatal fluoride exposure triggered neurotoxicity in the male offspring hippocampus was linked to synaptogenesis damage caused by activating p-Creb1, which disrupted the BDNF-TrkB pathway.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113682DOI Listing
July 2022

Periprocedural Outcomes Associated With Use of a Left Atrial Appendage Occlusion Device in China.

JAMA Netw Open 2022 05 2;5(5):e2214594. Epub 2022 May 2.

Department of Cardiology, Xijing Hospital, Xi'an, China.

Importance: Left atrial appendage occlusion (LAAO) has emerged as an alternative to anticoagulation for patients with atrial fibrillation. However, the performance of LAAO among East Asian patients is unknown.

Objective: To document the procedural success rate and configurations, major adverse event rates, and antithrombotic medication regimens during and after LAAO procedures among patients in China.

Design, Setting, And Participants: In this cohort study, consecutive patients from 39 Chinese centers undergoing LAAO were prospectively enrolled between April 1, 2019, and October 31, 2020. Periprocedural and intraprocedural techniques and postprocedural medications were left to the surgeon's discretion. Data were analyzed from July 1 to November 1, 2021.

Exposure: LAAO for patients with atrial fibrillation.

Main Outcomes And Measures: The main outcomes were procedural success and complication rates periprocedure and major adverse event rates of death, stroke, systemic embolism, and bleeding events at 30 days postprocedure; the composite end point of death, stroke, and systemic embolism was also analyzed. Unadjusted and multivariable-adjusted logistic regression analyses were performed to assess the associations of periprocedural techniques (types of anesthesia, intraprocedural imaging modalities, and combined ablation procedure) with 30-day adverse events.

Results: Among 3096 enrolled participants, 1782 participants (57.6%) were men, and the mean (SD) age was 69 (9) years. Participants had a high risk of stroke (mean [SD] cardiovascular risk score, 4.0 [1.8]) and a moderate-to-high risk of bleeding (mean [SD] bleeding risk score, 2.4 [1.2]). A total of 1287 procedures (41.6%) were performed under local anesthesia, while 493 procedures (15.9%) used only fluoroscopy guidance. In 1297 procedures (41.9%), LAAO implantation was combined with radiofrequency ablation or cryoablation for atrial fibrillation. Procedural success was achieved in 3032 patients (97.9%). At 30-day follow-up, the rate of the composite end point of death, stroke, or systemic embolism was 0.52% (95% CI, 0.32%-0.84%), and the rate of any life-threatening or major bleeding was 1.23% (95% CI, 0.90%-1.68%). No significant associations were observed between the procedural success or 30-day adverse events and the types of anesthesia (general or local), intraprocedural imaging (transesophageal echocardiography, fluoroscopy, or intracardiac echocardiography), or whether a combined ablation procedure was performed or not. In centers performing at least 40 procedures per year, compared with those performing fewer than 40 procedures per year, procedural success was significantly higher (adjusted odd ratio [aOR], 1.97; 95% CI, 1.01-3.53; P = .02) and risk of life-threatening or major bleeding was significantly lower (aOR, 0.42; 95% CI, 0.21-0.87; P = .02).

Conclusions And Relevance: These findings suggest that patients with a high risk of stroke and moderate to high risk of bleeding who underwent implantation of a LAAO device in Chinese centers had high rates of procedural success and low rates of short-term ischemic and bleeding events.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.14594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157261PMC
May 2022

Determination of Transdermal Rate of Metallic Microneedle Array through an Impedance Measurements-Based Numerical Check Screening Algorithm.

Micromachines (Basel) 2022 Apr 30;13(5). Epub 2022 Apr 30.

School of Electronics and Information Technology, State Key Laboratory of Optoelectronic Materials and Technologies, Guangdong Province Key Laboratory of Display Material and Technology, Sun Yat-Sen University, Guangzhou 510006, China.

Microneedle systems have been widely used in health monitoring, painless drug delivery, and medical cosmetology. Although many studies on microneedle materials, structures, and applications have been conducted, the applications of microneedles often suffered from issues of inconsistent penetration rates due to the complication of skin-microneedle interface. In this study, we demonstrated a methodology of determination of transdermal rate of metallic microneedle array through impedance measurements-based numerical check screening algorithm. Metallic sheet microneedle array sensors with different sizes were fabricated to evaluate different transdermal rates. In vitro sensing of hydrogen peroxide confirmed the effect of transdermal rate on the sensing outcomes. An FEM simulation model of a microneedle array revealed the monotonous relation between the transdermal state and test current. Accordingly, two methods were primely derived to calculate the transdermal rate from the test current. First, an exact logic method provided the number of unpenetrated tips per sheet, but it required more rigorous testing results. Second, a fuzzy logic method provided an approximate transdermal rate on adjacent areas, being more applicable and robust to errors. Real-time transdermal rate estimation may be essential for improving the performance of microneedle systems, and this study provides various fundaments toward that goal.
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http://dx.doi.org/10.3390/mi13050718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9146767PMC
April 2022
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