Publications by authors named "Ling Chen"

2,825 Publications

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Seroprevalence of neutralizing antibodies against adenovirus type 26 and 35 in healthy populations from Guangdong and Shandong provinces, China.

Virol Sin 2022 Jun 25. Epub 2022 Jun 25.

Center for Infection and Immunity, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China. Electronic address:

Human adenoviruses type 26 (HAdV26) and type 35 (HAdV35) have increasingly become the choice of adenovirus vectors for vaccine application. However, the population pre-existing immunity to these two adenoviruses in China, which may reduce vaccine efficacy, remains largely unknown. Here, we established micro-neutralizing (MN) assays to investigate the seroprevalence of neutralizing antibodies (nAbs) against HAdV26 and HAdV35 in the general population of Guangdong and Shandong provinces, China. A total of 1,184 serum samples were collected, 47.0% and 15.8% of which showed HAdV26 and HAdV35 nAb activity, respectively. HAdV26-seropositive individuals tended to have more moderate nAbs titers (201-1000), while HAdV35-seropositive individuals appeared to have more low nAbs titers (72-200). The seropositive rates of HAdV26 and HAdV35 in individuals younger than 20 years old were very low. The seropositive rates of HAdV26 increased with age before 70 years old and decreased thereafter, while HAdV35 seropositive rates did not show similar characteristics. Notably, the seropositive rates and nAb levels of both HAdV26 and HAdV35 were higher in Guangdong Province than in Shandong Province, but did not exert significant differences between males and females. The seroprevalence between HAdV26 and HAdV35 showed little correlation, and no significant cross-neutralizing activity was detected. These results clarified the characteristics of the herd immunity against HAdV26 and HAdV35, and provided information for the rational development and application of HAdV26 and HAdV35 as vaccine vectors in China.
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http://dx.doi.org/10.1016/j.virs.2022.06.006DOI Listing
June 2022

Hypoxia-induced polypoid giant cancer cells in glioma promote the transformation of tumor-associated macrophages to a tumor-supportive phenotype.

CNS Neurosci Ther 2022 Jun 28. Epub 2022 Jun 28.

Department of Neurosurgery, Chinese PLA General Hospital, Beijing, China.

Aims: Polypoid giant cancer cells (PGCCs) represent a unique subgroup of stem-like cells, acting as a critical factor in promoting the recurrence of various solid tumors. The effect of PGCCs on the tumor malignancy of glioma and its immune microenvironment remains unclear.

Methods: Bioinformatic analysis was performed to investigate the relationship between M2 tumor-associated macrophages (TAMs) infiltration and survival of glioblastoma (GBM) patients. The spatial location of M2 TAMs in GBM was also investigated using the Ivy Glioblastoma Atlas Project (Ivy GAP) database. PGCCs were quantified in glioma of different grades. CoCl was used to induce PGCCs in cultures of A172 cells. PGCCs, and their progeny cells in cultures were further evaluated for morphological features, tumorsphere formation, and TAMs activation.

Results: The magnitude of M2 TAMs infiltration is significantly correlated with poor survival in GBM patients. M2 TAMs were enriched in the perinecrotic zone (PNZ) of GBM and positively correlated with hypoxic levels. Increased PGCCs were detected in glioma specimens of higher grades. CoCl induced hypoxia and the transformation of A172 cultures into PGCCs, producing the progeny cells, PGCCs-Dau, through asymmetric division. PGCCs and PGCCs-Dau possessed tumor stem cell-like features, while PGCCs-Dau enhanced the polarization of TAMs into an M2 phenotype with relevance to immunosuppression and malignancy in GBM.

Conclusions: PGCCs promote malignancy and immune-suppressive microenvironment in GBM. PGCCs or their progeny cells may be a potential therapeutic target for GBM.
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http://dx.doi.org/10.1111/cns.13892DOI Listing
June 2022

Statistical estimation and comparison of group-specific bivariate correlation coefficients in family-type clustered studies.

J Appl Stat 2022 18;49(9):2246-2270. Epub 2021 Mar 18.

Department of Neurology, Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.

Bivariate correlation coefficients (BCCs) are often calculated to gauge the relationship between two variables in medical research. In a family-type clustered design where multiple participants from same units/families are enrolled, BCCs can be defined and estimated at various hierarchical levels (subject level, family level and marginal BCC). Heterogeneity usually exists between subject groups and, as a result, subject level BCCs may differ between subject groups. In the framework of bivariate linear mixed effects modeling, we define and estimate BCCs at various hierarchical levels in a family-type clustered design, accommodating subject group heterogeneity. Simplified and modified asymptotic confidence intervals are constructed to the BCC differences and Wald type tests are conducted. A real-world family-type clustered study of Alzheimer disease (AD) is analyzed to estimate and compare BCCs among well-established AD biomarkers between mutation carriers and non-carriers in autosomal dominant AD asymptomatic individuals. Extensive simulation studies are conducted across a wide range of scenarios to evaluate the performance of the proposed estimators and the type-I error rate and power of the proposed statistical tests. Abbreviations: BCC: bivariate correlation coefficient; BLM: bivariate linear mixed effects model; CI: confidence interval; AD: Alzheimer's disease; DIAN: The Dominantly Inherited Alzheimer Network; SA: simple asymptotic; MA: modified asymptotic.
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http://dx.doi.org/10.1080/02664763.2021.1899141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225315PMC
March 2021

Risk factors of extrauterine growth restriction in very preterm infants with bronchopulmonary dysplasia: a multi-center study in China.

BMC Pediatr 2022 Jun 24;22(1):363. Epub 2022 Jun 24.

Department of Pediatrics, Peking University Third Hospital, Beijing, China.

Objective: Nutritional deficiency soon after birth is a risk factor of chronic lung disease (bronchopulmonary dysplasia, BPD). Afflicted infants are further prone to inadequate growth during hospitalization (extrauterine growth restriction, EUGR). This multi-center retrospective study investigated risk factors of EUGR, specifically in very preterm infants with BPD.

Method: Data of infants with BPD who were born less than 32 weeks gestation (n = 1010) were collected from 7 regions of China. All infants were non-small for gestational age at birth. Infants were characterized as EUGR or non-EUGR at 36 weeks gestation or discharge, or stratified by gestational age or birthweight. Logistic regression analysis was applied.

Results: In 65.5% of the population, the BPD was mild. Infants with severe BPD (8.3%) had the highest rate of EUGR (72.6%, P < 0.001). Groups stratified by gestational age did not differ in rates of EUGR, but the birthweight of the EUGR group was significantly lower than that of the non-EUGR (P < 0.001). Birthweights of < 1000, 1000-1499, and ≥ 1500 g showed EUGR rates of 65.9%, 43.4%, and 23.8%, respectively (P < 0.001). Overall, the independent risk factors of EUGR were: moderate-to-severe BPD, gestational hypertension, cesarean section, cumulative fasting time, time required to achieve 110 kcal/kg/d, and hemodynamically significant patent ductus arteriosus (hsPDA).

Conclusion: In very preterm infants with BPD, the lower the birthweight or the more severe the BPD, the greater the risk of EUGR. In those with hsPDA, or moderate-to-severe BPD, it is especially important to prevent EUGR through perinatal management, enteral nutrition, and nutritional strategies.
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http://dx.doi.org/10.1186/s12887-022-03405-zDOI Listing
June 2022

Nanosilicate-Reinforced Silk Fibroin Hydrogel for Endogenous Regeneration of both Cartilage and Subchondral Bone.

Adv Healthc Mater 2022 Jun 24:e2200602. Epub 2022 Jun 24.

School of Medicine, Southeast University, Nanjing, 210009, China.

Osteochondral defects are characterized by injuries to both cartilage and subchondral bone, which is a result of trauma, inflammation, or inappropriate loading. Due to the unique biological properties of subchondral bone and cartilage, developing a tissue engineering scaffold that can promote dual-lineage regeneration of cartilage and bone simultaneously remains a great challenge. In this study, we fabricated a microporous nanosilicate-reinforced enzymatically-crosslinked silk fibroin (SF) hydrogel by introducing two-dimensional montmorillonite (MMT) nanoparticles via intercalation chemistry. In vitro studies showed that SF-MMT nanocomposite hydrogel had improved mechanical properties and hydrophilicity, as well as the bioactivities to promote the osteogenic differentiation of bone marrow stem cells (BMSCs) with an increased ALP activity and calcium deposition and maintain chondrocyte phenotype with a higher aggrecan expression and a lower matrix-degrading enzyme expression (MMP3/13, ADAMTS4/5) compared with SF hydrogel. Global proteomic analysis verified the dual-lineage bioactivities of SF-MMT nanocomposite hydrogel, which were probably regulated by multiple signaling pathways. Besides, it was observed that the biophysical interaction of cells and SF-MMT nanocomposite hydrogel was partially mediated by clathrin-mediated endocytosis and its downstream processes. In vivo, SF-MMT nanocomposite hydrogel effectively promoted subchondral bone and cartilage regeneration in rabbit osteochondral defect model as evidenced by macroscopic, micro-CT, and histological evaluation. In conclusion, we developed a functionalized SF-MMT nanocomposite hydrogel with dual-lineage bioactivity for osteochondral regeneration, indicating its potential in osteochondral tissue engineering. Statement of significance Osteochondral defects involve the injuries of both articular cartilage and subchondral bone. Due to the distinct properties of these two tissues, it remains a great challenge to induce the dual-lineage regeneration of cartilage and bone simultaneously. This study developed an SF-MMT nanocomposite hydrogel by enzymatic crosslinking and intercalation chemistry, which effectively enhanced the osteogenic differentiation of BMSCs and the maintenance of chondrocyte phenotype, thereby promoting the dual-lineage regeneration of articular cartilage and subchondral bone in osteochondral defects. Therefore, SF-MMT nanocomposite hydrogel with dual-lineage bioactivity is a promising scaffold for osteochondral tissue engineering. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adhm.202200602DOI Listing
June 2022

Reduction in RF Loss Based on AlGaN Back-Barrier Structure Changes.

Micromachines (Basel) 2022 May 26;13(6). Epub 2022 May 26.

The Engineering Research Center for Optoelectronics of Guangdong Province, School of Physics and Optoelectronics, South China University of Technology, Guangzhou 510640, China.

We designed a high electron mobility transistor (HEMT) epitaxial structure based on an AlGaN/GaN heterojunction, utilizing Silvaco TCAD, and selected AlGaN with an aluminum composition of 0.1 as the back-barrier of the AlGaN/GaN heterojunction. We enhanced the confinement of the two-dimensional electron gas (2DEG) by optimizing the structural parameters of the back barrier, so that the leakage current of the buffer layer is reduced. Through these optimization methods, a lower drain leakage current and a good radio frequency performance were obtained. The device has a cut-off frequency of 48.9 GHz, a maximum oscillation frequency of 73.20 GHz, and a radio frequency loss of 0.239 dB/mm (at 6 GHz). This work provides a basis for the preparation of radio frequency devices with excellent frequency characteristics and low RF loss.
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http://dx.doi.org/10.3390/mi13060830DOI Listing
May 2022

Efficacy of Topical Intervention for Recurrent Aphthous Stomatitis: A Network Meta-Analysis.

Medicina (Kaunas) 2022 Jun 7;58(6). Epub 2022 Jun 7.

The Center of Experimental Teaching Management, Chongqing Medical University, Chongqing 400016, China.

To compare the efficacy and safety of topical interventions used for recurrent aphthous stomatitis. This network meta-analysis was conducted in accordance with the PRISMA statement. We searched four electronic databases, PubMed, Web of Science (WOS), Cochrane Central Register of Controlled Trials and Embase, for randomized controlled trials reporting efficacy and safety data on topical interventions for recurrent aphthous stomatitis. We performed a quality evaluation using a methodology based on the Cochrane Handbook. Two authors independently extracted data on healing effect, size reduction effect, symptom reduction effect, recurrence and safety assessment. Network meta-analysis was then performed using ADDIS and RevMan. : A total of 72 trials (5272 subjects) involving 29 topical interventions were included. Honey, lnsulin liposome gel, laser, amlexanox, glycyrrhiza and triamcinolone had better efficacy performance. Probiotics and chlorhexidine helped to prolong ulcer intervals and reduce recurrence. Doxycycline and penicillin had a high risk of adverse events. Hematologic evaluation showed no preference. The rank possibility of size-reducing effect and symptom-reducing effect supported the short-term effect of laser and the long-term effect of probiotics. : We recommend the use of laser as a short-term intervention during the exacerbation phase of RAS and probiotics as a long-term intervention during the exacerbation and remission phases of RAS.
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http://dx.doi.org/10.3390/medicina58060771DOI Listing
June 2022

Unveiling a Novel Source of Resistance to Bacterial Blight in Medicinal Wild Rice, .

Life (Basel) 2022 Jun 2;12(6). Epub 2022 Jun 2.

Biotechnology and Germplasm Resources Institute, Yunnan Academy of Agricultural Sciences, Yunnan Provincial Key Lab of Agricultural Biotechnology, Ministry of Agriculture, Kunming 650205, China.

Bacterial blight (BB) caused by pv. () is among the oldest known bacterial diseases found for rice in Asia. It is the most serious bacterial disease in many rice growing regions of the world. A total of 47 resistance (R) genes ( to ) have been identified. Nonetheless, these R genes could possibly be defeated to lose their qualitative nature and express intermediate phenotypes. The identification of sources of novel genetic loci regulating host plant resistance is crucial to develop an efficient control strategy. Wild ancestors of cultivated rice are a natural genetic resource contain a large number of excellent genes. Medicinal wild rice () belongs to the CC genome and is a well-known wild rice in south China. In this study, was crossed with cultivated rice HY-8 and their hybrids were screened for BB resistance genes deployed through natural selection in wild rice germplasm. The molecular markers linked to R genes for BB were used to screen the genomic regions in wild parents and their recombinants. The gene coding and promoter regions of major R genes were inconsistently found in and its progenies. showed resistance to all thirty inoculated strains with non-availability of various known R genes. The results indicated the presence of novel genomic regions for BB resistance in . The present study not only provides a reference to investigate medicinal rice for R gene(s) identification against BB but also identified it as a new breeding material for BB resistance.
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http://dx.doi.org/10.3390/life12060827DOI Listing
June 2022

The Developmental Delay of Seedlings With Cotyledons Only Confers Stress Tolerance to (Chenopodiaceae) by Unique Performance on Morphology, Physiology, and Gene Expression.

Front Plant Sci 2022 6;13:844430. Epub 2022 Jun 6.

Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, China.

Cotyledons play an important role in seedling establishment, although they may just exist for a short time and become senescent upon the emergence of euphylla. So far, the detailed function of cotyledons has not been well understood. is an annual halophyte distributed in cold deserts; its cotyledons could exist for a longer time, even last until maturity, and they must exert a unique function in seedling development. Therefore, in this study, we conducted a series of experiments to investigate the morphological and physiological performances of cotyledons under salt stress at different developmental stages. The results showed that the cotyledons kept growing slowly to maintain the normal physiological activities of seedlings by balancing phytohormone levels, accumulating osmoprotectants and antioxidants, and scavenging reactive oxygen species (ROS). Salt stress activated the expression of osmoprotectant-related genes and enhanced the accumulation of related primary metabolites. Furthermore, differentially expressed transcriptional profiles of the cotyledons were also analyzed by cDNA-AFLP to gain an understanding of cotyledons in response to development and salt stress, and the results revealed a progressive increase in the expression level of development-related genes, which accounted for a majority of the total tested TDFs. Meanwhile, key photosynthetic and important salt stress-related genes also actively responded. All these performances suggest that "big cotyledons" are experiencing a delayed but active developmental process, by which may survive the harsh condition of the seedling stage.
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http://dx.doi.org/10.3389/fpls.2022.844430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9208309PMC
June 2022

[Corrigendum] BMI‑1 promotes invasion and metastasis in endometrial adenocarcinoma and is a poor prognostic factor.

Oncol Rep 2022 Aug 22;48(2). Epub 2022 Jun 22.

Department of Obstetrics and Gynecology, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong 264100, P.R. China.

Following the publication of the above paper, an interested reader drew to the authors' attention that, in Fig. 5 on p. 1637, the data panel selected to represent the 'Ishikawa/+BMI‑1 siRNA/Invasion' experiment in Fig. 5A appeared to overlap with the data shown for the 'JEC/+BMI‑1 siRNA/Migration' panel in Fig. 5C, such that they were potentially derived from the same original source. The authors have re‑examined their original data, and realize that the data panel selected for the 'Ishikawa/+BMI‑1 siRNA/Invasion' experiment in Fig. 5A was inadvertently selected incorrectly. The corrected version of Fig. 5, showing the correct data for the 'Ishikawa/+BMI‑1 siRNA/Invasion' experiment in Fig. 5A, is shown below. Note that this error did not affect the overall conclusions reported in the study. The authors are grateful to the Editor of for granting them the opportunity to publish this Corrigendum; furthermore, they apologize for any inconvenience caused to the readership of the Journal. [Oncology Reports 43: 1630‑1640, 2020; DOI: 10.3892/or.2020.7539].
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http://dx.doi.org/10.3892/or.2022.8352DOI Listing
August 2022

3D-printing of oxidized starch-based hydrogels with superior hydration properties.

Carbohydr Polym 2022 Sep 3;292:119686. Epub 2022 Jun 3.

School of Food Science and Engineering, Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, Engineering Research Center of Starch and Vegetable Protein Processing Ministry of Education, South China University of Technology, Guangzhou 510640, China. Electronic address:

High-hydration hydrogels based on carbohydrate polymers and green preparation methods have attracted intensive research focus recently. Driven by the attractive functions of starch, oxidized maize starch (OMS) was chosen and the related hydrogel (3D-OMS) was constructed by hot-extrusion 3D printing (HE-3DP). Meanwhile, the effect of different OMS concentrations (11 %-19 %) on its printability, structure and hydration properties were systematically investigated. The results showed that the formation of porous structure during HE-3DP environment contributed to rapid water absorption and well water holding capacity of 3D-OMS. Interestingly, as the OMS concentration increased from 11 % to 19 %, the 3D-OMS presented great hydration properties, with its maximum water absorption capacity and water holding capacity reaching 3013.43 % (11-OMS) and 93.53 % (19-OMS), respectively. Among them, 13 % was the best concentration for HE-3DP. Besides, 3D-OMS also exhibited good biodegradability and cytocompatibility. These results demonstrated potential for developing new starch-based biomedical hydrogel with great hydration properties through HE-3DP technology.
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http://dx.doi.org/10.1016/j.carbpol.2022.119686DOI Listing
September 2022

GSK-J4, a Specific Histone Lysine Demethylase 6A Inhibitor, Ameliorates Lipotoxicity to Cardiomyocytes Preserving H3K27 Methylation and Reducing Ferroptosis.

Front Cardiovasc Med 2022 2;9:907747. Epub 2022 Jun 2.

Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Changes in modern lifestyle provoke a series of metabolic stresses such as hyperlipidemia. Excessive free fatty acids induce cardiomyocyte metabolic reprogramming and rearrangement of the lipid content of cardiomyocyte and promote oxidative stress. As a newly defined lipid peroxidation-related cell death pathway, the role of ferroptosis in metabolic stress-induced cardiomyocyte injury is poorly revealed. Our work indicates that GSK-J4, a histone lysine demethylase 6A/6B dual inhibitor, can alleviate palmitic acid (PA)-induced hypersensitivity to ferroptosis by suppressing H3K27 demethylation. Mechanistically, PA stimulation reduces the H3K27me3 level and hence promotes the expression of ACSL4, a key lipid modulator of ferroptosis. GSK-J4 pretreatment significantly preserves the H3K27me3 level and reduces the ACSL4 level. GSK-J4 also reduces reactive oxygen species to alleviate oxidative stress, which further decreases lipid peroxidation. Taken together, our data suggest that cardiomyocyte undergoes epigenetic reprogramming under metabolic challenges, rearranging lipid content, and sensitizing to ferroptosis. GSK-J4 can be a potential drug for treating hyperlipidemia-induced cardiomyocyte injury by targeting epigenetic modulations.
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http://dx.doi.org/10.3389/fcvm.2022.907747DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200982PMC
June 2022

Three-dimensional-printed polycaprolactone scaffolds with interconnected hollow-pipe structures for enhanced bone regeneration.

Regen Biomater 2022 30;9:rbac033. Epub 2022 May 30.

Department of Orthopaedic Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, China.

Three-dimensional (3D)-printed scaffolds are widely used in tissue engineering to help regenerate critical-sized bone defects. However, conventional scaffolds possess relatively simple porous structures that limit the delivery of oxygen and nutrients to cells, leading to insufficient bone regeneration. Accordingly, in the present study, perfusable and permeable polycaprolactone scaffolds with highly interconnected hollow-pipe structures that mimic natural micro-vascular networks are prepared by an indirect one-pot 3D-printing method. experiments demonstrate that hollow-pipe-structured (HPS) scaffolds promote cell attachment, proliferation, osteogenesis and angiogenesis compared to the normal non-hollow-pipe-structured scaffolds. Furthermore, studies reveal that HPS scaffolds enhance bone regeneration and vascularization in rabbit bone defects, as observed at 8 and 12 weeks, respectively. Thus, the fabricated HPS scaffolds are promising candidates for the repair of critical-sized bone defects.
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http://dx.doi.org/10.1093/rb/rbac033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201971PMC
May 2022

Fasting serum glucose and lymph node metastasis in non-diabetic PTC patients: a 10-Year multicenter retrospective study.

J Cancer 2022 20;13(8):2673-2682. Epub 2022 May 20.

Department of Thyroid Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Mostly current studies are limited to the impact of lymph node metastasis(LNM) on the prognosis of papillary thyroid cancer(PTC) or the impact of glucose metabolism on the occurrence of PTC, but no one has paid attention to the connection between fasting serum glucose(FSG) and LNM. The purpose of our study was to explore the relationship between FSG and LNM in non-diabetic PTC patients. In this study, we performed a multicenter, retrospective study on 6034 non-diabetic patients with PTC. The associations of FSG with three types of LNM including central lymph node metastasis (CLNM), lateral cervical lymph node metastasis (LLNM) and both were estimated. Compared with PTC patients without LNM, those with LNM had higher FSG. We also found that FSG was associated with tumor extension, maximum tumor diameter and TSH. In order to further explore the association between FSG and different types of LNM, we analyzed three groups of data separately. Our study reveals that by comparing FSG between patients without LNM and patients with three LNM types, it was statistically different in the PTC patients with CLNM and the PTC patients with CLNM combined with LLNM. Our study provides evidence for the association of FSG and LNM in non-diabetic PTC patients, with a gradual increase in FSG over the course of the PTC from no lymph node metastasis to CLNM combined with LLNM. Meanwhile, higher FSG is a risk factor for CLNM and CLNM combined with LLNM. In the future, FSG might be used as an indicator for lymph node dissection in PTC patients. However, larger relative studies are needed.
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http://dx.doi.org/10.7150/jca.71514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174864PMC
May 2022

Exploration of Different Hypoxia Patterns and Construction of a Hypoxia-Related Gene Prognostic Index in Colorectal Cancer.

Front Immunol 2022 30;13:853352. Epub 2022 May 30.

Department of Radiotherapy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Introduction: Immune checkpoint inhibitor (ICI) therapy has been proven to be a highly efficacious treatment for colorectal adenocarcinoma (COAD). However, it is still unclear how to identify those who might benefit the most from ICI therapy. Hypoxia facilitates the progression of the tumor from different aspects, including proliferation, metabolism, angiogenesis, and migration, and improves resistance to ICI. Therefore, it is essential to conduct a comprehensive understanding of the influences of hypoxia in COAD and identify a biomarker for predicting the benefit of ICI.

Methods: An unsupervised consensus clustering algorithm was used to identify distinct hypoxia-related patterns for COAD patients from TCGA and the GEO cohorts. The ssGSEA algorithm was then used to explore the different biological processes, KEGG pathways, and immune characteristics among distinct hypoxia-related clusters. Some hypoxia-related hub genes were then selected by weighted gene coexpression network analysis (WGCNA). Subsequently, univariate Cox regression analysis, multivariate Cox regression analysis, and least absolute shrinkage and selection operator (LASSO) regression were utilized to construct a hypoxia-related gene prognostic index (HRGPI). Finally, validation was also conducted for HRGPI in prognostic value, distinguishing hypoxia-related characteristics and benefits of ICI.

Results: We identified four hypoxia-related clusters and found that different hypoxia response patterns induced different prognoses significantly. Again, we found different hypoxia response patterns presented distinct characteristics of biological processes, signaling pathways, and immune features. Severe hypoxia conditions promoted activation of some cancer-related signaling pathways, including Wnt, Notch, ECM-related pathways, and remodeled the tumor microenvironment of COAD, tending to present as an immune-excluded phenotype. Subsequently, we selected nine genes (ANO1, HOXC6, SLC2A4, VIP, CD1A, STC2, OLFM2, ATP6V1B1, HMCN2) to construct our HRGPI, which has shown an excellent prognostic value. Finally, we found that HRGPI has an advantage in distinguishing immune and molecular characteristics of hypoxia response patterns, and it could also be an excellent predictive indicator for clinical response to ICI therapy.

Conclusion: Different hypoxia response patterns activate different signaling pathways, presenting distinct biological processes and immune features. HRGPI is an independent prognostic factor for COAD patients, and it could also be used as an excellent predictive indicator for clinical response to ICI therapy.
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http://dx.doi.org/10.3389/fimmu.2022.853352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196334PMC
June 2022

Longitudinal analysis reveals age-related changes in the T cell receptor repertoire of human T cell subsets.

J Clin Invest 2022 Jun 16. Epub 2022 Jun 16.

Laboratory of Molecular Biology and Immunology, National Institute on Aging, NIH, Baltimore, United States of America.

A diverse T cell receptor (TCR) repertoire is essential for protection against a variety of pathogens and T cell repertoire size is believed to decline with age. However, the precise size of human TCR repertoire in total and subsets of T cells, and their changes with age are not fully characterized. We conducted a longitudinal analysis of the human blood TCRα and TCRβ repertoire of CD4+ and CD8+ T cell subsets using a unique molecular identifier (UMI) based RNAseq method. Thorough analysis of 1.9 x 108 T cells yielded the lower estimate of TCR repertoire richness in an adult at 3.8 x 108. Alterations of TCR repertoire with age were observed in all four subsets of T cells. The greatest reduction was observed in naïve CD8+ T cells; the greatest clonal expansion was in memory CD8+ T cells, and the highest increased retention of TCR sequences was in memory CD8+ T cells. Our results demonstrated that age-related TCR repertoire attrition is subset specific and more profound for CD8+ than CD4+ T cells, suggesting aging has a more profound impact on the cytotoxic than on the helper T cell functions. This may explain the increased susceptibility of older adults to the novel infections.
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http://dx.doi.org/10.1172/JCI158122DOI Listing
June 2022

The Utilization of Dual Second Sacral Alar-Iliac Screws for Spinopelvic Fixation in Patients with Severe Kyphoscoliosis.

Orthop Surg 2022 Jun 13. Epub 2022 Jun 13.

Department of Spine Surgery, Nanjing Drum Tower Hospital, The Clinical College of Nanjing Medical University, Nanjing, 210008, China.

Objectives: As a new pelvic fixation technique, the dual S2AI screws fixation technique could provide highly stable distal strength, and have wide clinical prospect in the correction of severe kyphoscoliosis. However, the ideal trajectory parameters, indications and clinical outcomes of this technique have not been reported so far. This study aimed to determine the anatomical parameters of dual S2AI screws in the normal Chinese adult population, investigating the indications of this technique and evaluating the feasibility and clinical outcomes.

Methods: Fifteen males and 15 females with normal pelvis underwent a pelvic CT scan to determine ideal dual S2AI screws trajectories. Sagittal angle (SA), transverse angle (TA), maximal length (ML), sacral length, and skin distance were measured. Subsequently, we retrospectively reviewed the data of 16 patients (seven males and nine females) who underwent dual S2AI screw fixation and 23 patients who underwent single S2AI screw fixation between January 2014 and December 2019. Preoperative, postoperative, and latest follow-up measurements of Cobb angle, coronal balance (CB), spinal pelvic obliquity (SPO), and regional kyphosis (RK) were obtained. The mean follow-up time was 16.7 ± 7.1 months (range: 12-30 months). Independent t-test was used to determine the difference in the analysis of the trajectories. The paired sample non-parametric Wilcoxon test was performed to assess the changes in radiographic parameters between different time points and different groups.

Results: For both male and females, the proximal S2AI screws had significantly higher TA and ML, but a lower SA than distal screws. Females showed significantly more caudal (SA: 25.03° ± 2.32° vs. 29.82° ± 2.47°, t = 7.742, P < 0.001) trajectories of distal screw. Additionally, ML in the females were significantly shorter than that in males (106.81 mm ± 6.79 mm vs. 101.63 mm ± 6.55 mm, t = 3.007, P = 0.003, 124.41 mm ± 7.57 mm vs. 116.23 mm ± 7.03 mm, t = 4.337, P < 0.001). Eight had unilateral and eight had bilateral dual S2AI screw placement. Respectively, both the single S2AI and dual S2AI groups showed significant postoperative improvement of Cobb angle, RK angle and SPO angle. In patients with dual S2AI screws fixation, two patients found that screws loosening occurred in one of dual screws at 1-year follow-up, and in patients with single S2AI screws fixation, six patients found screw loosing as well as two patients found screw breakage at 1-year follow-up. None of all patients had any prominent loss of correction.

Conclusion: The ideal trajectory of dual S2AI screw could be well established. The dual S2AI screw fixation technique is feasible in patients with severe kyphoscoliosis, and provides satisfactory correction of deformity with few postoperative complications.
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http://dx.doi.org/10.1111/os.13348DOI Listing
June 2022

Clinical relevance of glomerular C4d deposition in children with early IgA nephropathy or Henoch-Schönlein purpura nephropathy.

Pediatr Nephrol 2022 Jun 13. Epub 2022 Jun 13.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28th Fuxing Road, Beijing, 100045, China.

Background: Both IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephropathy (HSPN) are characterized by glomerular mesangial IgA deposition. Several large studies on adults have suggested that glomerular C4d deposition has prognostic value in IgAN. However, there are few relevant studies on the clinical value of C4d deposition in children with IgAN or HSPN.

Methods: We performed a retrospective cohort study in pediatric patients with IgAN or HSPN. Clinicopathological data were collected at the time of kidney biopsy. Kidney C4d deposition was analyzed by immunohistochemistry. The end point was defined as a ≥ 20% decrease in estimated glomerular filtration from baseline.

Results: We enrolled 75 children, including 36 children with IgAN and 39 with HSPN. The prevalence of C4d deposition was 36% (27/75). C4d deposition was more abundant in children with proteinuria ≥ 50 mg/kg/day (51.9% versus 20.8%, P = 0.006) or nephrotic syndrome (37.0% versus 10.4%, P = 0.006). Mesangial hypercellularity (hazard ratio [HR], 5.745, 95% confidence interval [CI], 1.670-19.761, P = 0.006) and IgM deposition (HR, 4.522, 95% CI, 1.321-15.478, P = 0.016) were associated with C4d deposition. After a median follow-up of 22 months, seven (19.4%) IgAN patients and one (2.6%) HSPN patient had decreased kidney function. In children with IgAN, positive C4d was associated with decreased kidney function (P = 0.047).

Conclusion: Glomerular C4d deposition was associated with mesangial hypercellularity and glomerular IgM deposition in IgAN and HSPN. Glomerular C4d deposition may be a risk factor for eGFR decline in children with IgAN. A higher resolution version of the Graphical abstract is available as Supplementary information.
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http://dx.doi.org/10.1007/s00467-022-05585-3DOI Listing
June 2022

Contrast-enhanced ultrasonography for assessing histopathology in pediatric immunoglobulin A nephropathy and Henoch-Schönlein purpura nephritis.

Pediatr Radiol 2022 Jun 13. Epub 2022 Jun 13.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Background: Glomerular disease, including immunoglobulin A nephropathy (IgAN) and Henoch-Schönlein purpura nephritis, is one of the most common kidney diseases in children. The diagnosis of these diseases depends on pathological biopsy, although this procedure is seriously limited by its invasive and high-risk nature.

Objective: To investigate the potential of contrast-enhanced ultrasonography (CEUS) for evaluating the histopathological severity of IgAN and Henoch-Schönlein purpura nephritis (HSPN).

Materials And Methods: We investigated a total of 13 children with IgAN and 12 children with HSPN confirmed by renal histopathology. We reevaluated the pathological lesions of the children according to the Oxford classification and the Lee grading system and then all the children underwent CEUS. Using SonoLiver software, we constructed time-intensity curves of CEUS for regions of interest in the renal cortex. We analyzed CEUS quantitative parameters for IgAN and HSPN and used Spearman correlation analysis to examine the correlation between CEUS parameters and clinicopathological indexes in the study cohort.

Results: The CEUS parameters rise time (RT) and time to peak (TTP) were significantly higher in children with Lee grade IV than in those with Lee grades II or III. Spearman correlation analysis revealed a positive correlation between rise time and time to peak with Lee grade in the overall cohort of children, and a positive correlation between rise time and time to peak and severity of crescents in the Oxford classification scoring system.

Conclusion: Contrast-enhanced US may be used as a noninvasive imaging technique to evaluate the severity of renal pathology and formation of crescents in children with IgAN and HSPN.
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http://dx.doi.org/10.1007/s00247-022-05399-3DOI Listing
June 2022

Role of PGC-1α in fiber type conversion in the palatopharyngeus muscle of OSA patients.

J Clin Lab Anal 2022 Jun 12:e24551. Epub 2022 Jun 12.

Department of Otolaryngology-Head and Neck, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guang zhou, China.

Background: Obstructive sleep apnea (OSA) has a high incidence and is harmful to health. It is characterized by repeated collapse of the upper airway. However, the mechanism underlying upper airway collapse is unclear.

Methods: Patients with OSA and chronic tonsillitis were studied. Pathological changes in palatopharyngeus muscle were detected. The expression of peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) and nuclear respiratory factor-1 (NRF-1) in muscles was detected by PCR and Western blotting. Immunofluorescence staining was used to detect the expression of type I and type II myofibril.

Results: The structure of the palatopharyngeus muscle was changed, and the expression of PGC-1α and NRF-1 was decreased in the OSA group compared with that in the control group. The expression of PGC-1α, NRF-1, and type I myofibril in C2C12 myoblasts was decreased by intermittent hypoxia exposure. The expression of type I myofibril was decreased when knocking down PGC-1α.

Conclusion: OSA patients exhibited pathological damage in palatopharyngeus muscle. PGC-1α was involved in the fiber type conversion in palatopharyngeus muscle caused by intermittent hypoxia.
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http://dx.doi.org/10.1002/jcla.24551DOI Listing
June 2022

Detecting of mycoplasma genitalium infection in surgically treated infertile women.

Asian J Surg 2022 Jun 9. Epub 2022 Jun 9.

Department of Gynecology and Obstetrics, West China Second University Hospital of Sichuan University, Chengdu, PR China; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.asjsur.2022.05.126DOI Listing
June 2022

PCDHB14 promotes ferroptosis and is a novel tumor suppressor in hepatocellular carcinoma.

Oncogene 2022 Jun 10. Epub 2022 Jun 10.

Department of Pathology, Xiangya Hospital, Central South University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, Hunan, 410078, P. R. China.

Liver cancer, a result of multifactorial interplay between heredity and the environment, is one of the leading causes of cancer-related death worldwide. Hepatocellular carcinoma (HCC) is the most common histologic type of primary liver cancer. Here, we reported that deficiency in PCDHB14, a member of the cadherin superfamily, participates in the progression of HCC. We found that PCDHB14 is inactivated by aberrant methylation of its promoter in HCC patients and that PCDHB14 functions as a tumor suppressor to promote cell cycle arrest, inhibit cell proliferation, and induce ferroptosis. Furthermore, PCDHB14 ablation dramatically enhanced diethylenenitrite-induced HCC development. Mechanistically, PCDHB14 is induced by p53, and increased PCDHB14 downregulates the expression of SLC7A11, which is critical for ferroptosis. This effect is mediated by accelerated p65 protein degradation resulting from PCDHB14 promoting E3 ubiquitin ligase RNF182-mediated ubiquitination of p65 to block p65 binding to the promoter of SLC7A11. This study reports the new discovery that PCDHB14 serves as a potential prognostic marker for HCC.
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http://dx.doi.org/10.1038/s41388-022-02370-2DOI Listing
June 2022

Effect of starch-catechin interaction on regulation of starch digestibility during hot-extrusion 3D printing: Structural analysis and simulation study.

Food Chem 2022 Nov 4;393:133394. Epub 2022 Jun 4.

Department of Physics, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR. Electronic address:

Recent developments of hot-extrusion 3D printing (HE-3DP) have made it possible to manipulate starch digestibility. This work investigated the regulating mechanism of starch-catechin (EC) interactions on rice starch digestibility during HE-3DP by using modern analytical techniques and computational models. The results showed that the HE-3DP processing with starch-EC interactions could significantly decrease the starch digestibility (p < 0.05) due to the formation of ordered structures including short-range ordered structure, nano-aggregates and V-type crystalline structure. Meanwhile, molecular dynamics simulations were performed to reveal the mechanism of EC as an enzyme inhibitor to enhance the resistant starch contents of rice starch to 46.1%. Results showed that EC could loosely attach to starch chains, thereby facilitating binding to Trp59 of pancreatic α-amylase and preventing starch from binding to its active pocket. These findings provide useful structural information for EC to reduce starch digestibility in the HE-3DP environment.
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http://dx.doi.org/10.1016/j.foodchem.2022.133394DOI Listing
November 2022

Association between plasma growth arrest-specific protein 6 and carotid atherosclerosis in type 2 diabetes mellitus.

Nutr Metab Cardiovasc Dis 2022 May 19. Epub 2022 May 19.

Department of Endocrinology and Metabolism, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.

Background And Aims: Growth arrest-specific 6 protein (Gas6) has been established to play important roles in various biological processes, but little is currently known on the role of Gas6 signaling in humans. This research explored the association between Gas6 expression and carotid atherosclerosis (AS) in type 2 diabetes mellitus (T2DM).

Methods And Results: As many as 126 T2DM patients were recruited in this study and classified into two groups based on their carotid intima-media thickness (CIMT). Meanwhile, 50 healthy individuals were recruited for the normal control group (NC). The subgroups were compared in terms of clinical data and Gas6 expression levels. Gas6 levels were decreased in T2DM patients with or without AS compared to NC subjects (9.64 ± 1.41 ng/ml, 11.38 ± 2.08 ng/ml, and 13.64 ± 2.61 ng/ml, respectively) (p < 0.001). The interaction between Gas6 and AS in T2DM was analyzed by logistic regression model and receiver operating characteristic (ROC) curve analysis. Decreased Gas6 expression was an independent risk factor relevant to AS in T2DM (p = 0.027). The area under the ROC curve to estimate the diagnostic value of low Gas6 expression for AS in T2DM was 0.750. The correlation between Gas6 and other parameters was evaluated by Pearson correlation analysis and linear regression model. Body mass index (BMI), hemoglobin A1c (HbA1c) and tumor necrosis factor-α(TNF-α) were independently correlated with Gas6.

Conclusion: Low Gas6 expression is an independent risk factor for AS in T2DM. Gas6 expression is affected by BMI, HbA1c and TNF-α levels.
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http://dx.doi.org/10.1016/j.numecd.2022.05.007DOI Listing
May 2022

DigestPath: A benchmark dataset with challenge review for the pathological detection and segmentation of digestive-system.

Med Image Anal 2022 May 24;80:102485. Epub 2022 May 24.

Mathematics for Real-World Systems Centre for Doctoral Training, University of Warwick, UK; Department of Computer Science, University of Warwick, UK.

Examination of pathological images is the golden standard for diagnosing and screening many kinds of cancers. Multiple datasets, benchmarks, and challenges have been released in recent years, resulting in significant improvements in computer-aided diagnosis (CAD) of related diseases. However, few existing works focus on the digestive system. We released two well-annotated benchmark datasets and organized challenges for the digestive-system pathological cell detection and tissue segmentation, in conjunction with the International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI). This paper first introduces the two released datasets, i.e., signet ring cell detection and colonoscopy tissue segmentation, with the descriptions of data collection, annotation, and potential uses. We also report the set-up, evaluation metrics, and top-performing methods and results of two challenge tasks for cell detection and tissue segmentation. In particular, the challenge received 234 effective submissions from 32 participating teams, where top-performing teams developed advancing approaches and tools for the CAD of digestive pathology. To the best of our knowledge, these are the first released publicly available datasets with corresponding challenges for the digestive-system pathological detection and segmentation. The related datasets and results provide new opportunities for the research and application of digestive pathology.
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http://dx.doi.org/10.1016/j.media.2022.102485DOI Listing
May 2022

Proteomics and post-translational modifications analysis of umbilical mesenchymal stem cells aging.

Anal Biochem 2022 Sep 3;652:114770. Epub 2022 Jun 3.

Laboratory of Interdisciplinary Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address:

Mesenchymal stem cells (MSCs) are considered to be critical for regenerative medicine. However, long-term culturing of MSCs will induce aging of MSCs, and thereafter impair cellular function. Changes in proteomics have been reported to be involved in cell aging, and therefore investigations on cell aging of MSCs at levels of proteomics and post-translational protein modifications (PTM) are ultimately important. In the present study, human umbilical cord mesenchymal stem cells (hUMSCs) were exposed to different culture conditions for either 7 or 30 days. Proteins changes during cell culture were investigated using tandem mass tag (TMT) labeling quantitative approach, and N-glycosylation patterns were analyzed using multistage mass spectrometry. We identified 66 proteins (fold change >1.50) that were differentially expressed in long-term culture. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that aging exerts a side effect on hUMSCs by affecting various molecular functions and biological processes, such as lysosome, autophagy and post-translational protein modification. Glycosylation analysis indicates that cell N-glycan patterns are associated with aging of MSCs. Our results presented here should contribute to future studies on cell aging and cellular quality controls related to MSCs as regenerative medicine.
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http://dx.doi.org/10.1016/j.ab.2022.114770DOI Listing
September 2022

The Efficacy and Safety of the Combined Therapy of Sodium-Glucose Co-Transporter-2 Inhibitors and Angiotensin Receptor-Neprilysin Inhibitor in Patients With Heart Failure With Reduced Ejection Fraction: A Meta-Analysis of the EMPEROR-Reduced and DAPA-HF Sub-Analysis.

Front Cardiovasc Med 2022 18;9:882089. Epub 2022 May 18.

Department of Geriatric Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, China.

Background: Both sodium-glucose co-transporter-2 (SGLT-2) inhibitors and angiotensin receptor-neprilysin inhibitor (ARNI) were recommended to treat heart failure with reduced ejection fraction (HFrEF). However, no trial was conducted to assess the efficacy and safety of the combined therapy of SGLT-2 inhibitors and ARNI in patients with HFrEF.

Methods: We performed a meta-analysis of the prespecified subgroups from DAPA-HF and EMPEROR-Reduced trials. The primary endpoint was the composite risk of cardiovascular death or hospitalization for heart failure. The risk of cardiovascular death, all-cause death, a composite of serious adverse renal outcomes, and volume depletion were also estimated.

Results: The risk of the composite of cardiovascular death or hospitalization for heart failure was reduced in combined therapy of SGLT-2 inhibitors and ARNI, compared with ARNI monotherapy (RR.68, 95% CI.53 to.85, = 0.001). When compared with SGLT-2 inhibitors monotherapy, the events of cardiovascular death (RR.64, 95% CI.46 to 0.87, = 0.005) and all-cause death (RR.72, 95% CI.55 to.94, = 0.01) were significantly less in combined therapy, accompanied by elevated incidence of volume depletion (RR 1.55, 95% CI 1.22 to 1.96, = 0.0003).

Conclusion: Combined therapy has additional benefits over monotherapy in patients with HFrEF, however, it is accompanied by a possibly higher risk of volume depletion.
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http://dx.doi.org/10.3389/fcvm.2022.882089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157547PMC
May 2022

Blockade of NLRP3/Caspase-1/IL-1 Regulated Th17/Treg Immune Imbalance and Attenuated the Neutrophilic Airway Inflammation in an Ovalbumin-Induced Murine Model of Asthma.

J Immunol Res 2022 25;2022:9444227. Epub 2022 May 25.

Department of Pediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Asthma is a heterogeneous inflammatory disorder of the airways, and multiple studies have addressed the vital role of the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)/caspase-1/interleukin-1 (IL-1) pathway in asthma, but its impact on ovalbumin- (OVA-) induced neutrophilic asthma remains unclear. Here, we explored this pathway's effect on airway inflammation in neutrophilic asthma to clarify whether blocking this signaling could alleviate asthmatic airway inflammation. Using an established OVA-induced neutrophilic asthma mouse model, we provided asthmatic mice with a highly selective NLRP3 inhibitor, MCC950, and a specific caspase-1 inhibitor, Ac-YVAD-cmk. Our results indicated that asthmatic mice exhibited increased airway hyperresponsiveness, neutrophil infiltration, and airway mucus hypersecretion, upregulated retinoid-related orphan receptor-t (RORt) mRNA expression, and downregulated fork head box p3 (Foxp3) mRNA expression, which was concurrent with NLRP3 inflammasome activation and upregulation of caspase-1, IL-1, and IL-18 expression in lung. Treatment of NLRP3 inflammasome inhibitors significantly attenuated airway hyperresponsiveness, airway inflammation, and reversed T helper 17 (Th17)/regulatory T (Treg) cell imbalance in asthmatic mice. We propose that the NLRP3/caspase-1/IL-1 pathway plays an important role in the pathological process of neutrophilic asthma and provides evidence that blocking this pathway could potentially be a treatment strategy to ameliorate airway inflammation in asthma after validation with future experimental and clinical studies.
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http://dx.doi.org/10.1155/2022/9444227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9159827PMC
June 2022

Durable complete response to neoantigen-loaded dendritic-cell vaccine following anti-PD-1 therapy in metastatic gastric cancer.

NPJ Precis Oncol 2022 Jun 3;6(1):34. Epub 2022 Jun 3.

BGI-Shenzhen, Shenzhen, 518083, China.

Absract: Neoantigens are ideal targets for dendritic cell (DC) vaccines. So far, only a few neoantigen-based DC vaccines have been investigated in clinical trials. Here, we reported a case of a patient with metastatic gastric cancer who received personalized neoantigen-loaded monocyte-derived dendritic cell (Neo-MoDC) vaccines followed by combination therapy of the Neo-MoDC and immune checkpoint inhibitor (ICI). The patient developed T cell responses against neoantigens after receiving the Neo-MoDC vaccine alone. The following combination therapy triggered a stronger immune response and mediated complete regression of all tumors for over 25 months till October, 2021. Peripheral blood mononuclear cells recognized seven of the eight vaccine neoantigens. And the frequency of neoantigen-specific T cell clones increased obviously after vaccination. Overall, this report describing a complete tumor regression in a gastric cancer patient mediated by Neo-MoDC vaccine in combination with ICI, and suggesting a promising treatment for patients with metastatic gastric cancer.
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http://dx.doi.org/10.1038/s41698-022-00279-3DOI Listing
June 2022

Different Binding Modes of SARS-CoV-1 and SARS-CoV-2 Fusion Peptides to Cell Membranes: The Influence of Peptide Helix Length.

J Phys Chem B 2022 Jun 6. Epub 2022 Jun 6.

Guizhou Provincial Key Laboratory of Computational Nano-Material Science, Guizhou Education University, Guiyang 550018, China.

Although the amino acid sequences of SARS-CoV-1 and SARS-CoV-2 fusion peptides (FPs) are highly conserved, the cryo-electron microscopy structures of the SARS-CoV-1 and SARS-CoV-2 spike proteins show that the helix length of SARS-CoV-1 FP is longer than that of SARS-CoV-2 FP. In this work, we simulated the membrane-binding models of SARS-CoV-1 and SARS-CoV-2 FPs and compared the binding modes of the FPs with the POPC/POPE/cholesterol bilayer membrane. Our simulation results show that the SARS-CoV-2 FP binds to the bilayer membrane more effectively than the SARS-CoV-1 FP. It is seen that the short N-terminal helix of SARS-CoV-2 FP is more favorable to insert into the target membrane than the long N-terminal helix of SARS-CoV-1 FP. Meanwhile, the potential of mean force calculations showed that the SARS-CoV-2 FP would prefer only one binding mode (N-terminal binding), whereas the SARS-CoV-1 FP has two favorable membrane-binding modes (C-terminal and N-terminal binding modes). Moreover, in the case of SARS-CoV-1 FP binding to the target membrane, the transition between the two binding modes is relatively fast. Finally, we discovered that the membrane-binding mode would influence the helix length of SARS-CoV-1 FP, while the helix length of SARS-CoV-2 FP could be stably maintained in the membrane-bound configurations. This work suggests that the short helix might endow the FP with high membrane-anchoring strength. In particular, the membrane-penetrating residues (Phe, Ile, and Leu) of short α-helix interact with the cell membrane more strongly than those of long α-helix.
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http://dx.doi.org/10.1021/acs.jpcb.2c01295DOI Listing
June 2022
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