Publications by authors named "Jing Zhu"

1,254 Publications

  • Page 1 of 1

A Patient-Controlled Intravenous Analgesia With Tramadol Ameliorates Postpartum Depression in High-Risk Woman After Cesarean Section: A Randomized Controlled Trial.

Front Med (Lausanne) 2021 27;8:679159. Epub 2021 May 27.

Department of Anesthesiology, Second Affiliated Hospital of Army Medical University, People's Liberation Army of China (PLA), Chongqing, China.

Postpartum depression (PPD) is a severe psychiatric disorder. Its risk is associated with the cesarean section (CS). Currently, there are few early intervention strategies for these women with PPD who underwent CS. This was a parallel-group randomized controlled trial of singleton pregnant women who underwent elective CS in a tertiary referral hospital in China from October, 2017 to September, 2019. After operation, patients received randomly tramadol patient-controlled intravenous analgesia (PCIA; 4 mg/ml; TRA group), hydromorphone PCIA (0.04 mg/ml; HYD group), or ropivacaine patient-controlled epidural analgesia (PCEA; 1.5 mg/ml; ROP group) for 48 h in a 1:1:1 ratio. Total blinding during hospitalization was not feasible due to differences between the PCEA and PCIA treatments. All investigators who performed the follow-up were blinded to the group assignment. A total of 1,230 patients were enrolled for eligibility. Intention-to-treat analysis showed reduced incidence of PPD in the TRA group ( = 27 [6.6%]) than that in the HYD (10.2%, OR 1.62, 95% CI 0.98~2.68; = 0.059) and ROP groups (10.5%, OR 1.66, 95% CI 1.01~2.75; = 0.046) at 4 weeks post-operation, however, the difference was not statistically significant (Bonferroni corrected = 0.118, = 0.098, respectively). Subgroup analysis in high-risk women (preoperative Edinburgh Postpartum Depression Scale [EPDS] ≥10) showed a significantly lower incidence of PPD in the TRA group (16.5%) than in the HYD (32.6%) and ROP groups (30.9%) (Bonferroni corrected = 0.022 and = 0.038, respectively). The per-protocol analysis yielded similar results. Reported adverse events (AEs) were mostly mild. None of the women or infant discontinued treatment due to AEs. Tramadol PCIA after CS in high-risk women can help to reduce the risk of PPD at 4 weeks after elective CS. https://clinicaltrials.gov/ct2/show/NCT03309163?term=ETPPD&draw=2&rank=1; ClinicalTrials.gov (NCT03309163).
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http://dx.doi.org/10.3389/fmed.2021.679159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191376PMC
May 2021

Online or Offline? How Smog Pollution Affects Customer Channel Choice for Purchasing Fresh Food.

Front Psychol 2021 26;12:682981. Epub 2021 May 26.

School of Business Administration, Faculty of Business Administration, Southwestern University of Finance and Economics, Chengdu, China.

Due to fresh foods' unique characteristics, where quality, freshness, and perishability are the main concerns, consumers are more inclined to choose offline channels for purchasing foods. However, it is not well-understood how these behaviors are affected by the adverse external environment, e.g., smog pollution. Fine particulate matters (PM2.5) on smog days would irritate the respiratory tract and pose health risks to people, triggering negative emotions such as sadness and depression. People tend to stay in a clean indoor environment on smog days. An adverse external environment is causing a gradual change in people's habits and emotions. Still, its impact on shopping behaviors is a complex process in need of further study. The study fills this gap by examining the impact of smog pollution on customer channel choice. Based on data from an e-commerce retailer that operates in both online and offline channels. We find that (1) the degree of smog pollution has a significant positive effect on online channel purchasing at aggregated store-, product-, and individual- levels; (2) moreover, the retailer's in-store interactive activities would restrain this positive relationship; (3) variation of product pricing and customers' healthy eating tendency would pronounce the positive association between smog and online purchasing. These results can serve as a reference for retailers to adjust channel strategies in the face of harsh external conditions.
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http://dx.doi.org/10.3389/fpsyg.2021.682981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188480PMC
May 2021

A retrospective analysis of prognostic factors for 160 patients with stage III small cell lung cancer.

Ann Palliat Med 2021 Jun 2. Epub 2021 Jun 2.

Department of Medical Thoracic Oncology, Jilin Provincial Cancer Hospital, Changchun, China.

Background: In some patients with stage III small cell lung cancer (SCLC), it is found that the treatment mode of systemic chemotherapy followed by auxiliary radiotherapy is better than early radiotherapy, but there is no clear evidence-based medical explanation for this. This study was designed to retrospectively evaluate prognostic factors for patients with stage III SCLC and explore the best treatment mode for locally advanced SCLC.

Methods: A total of 160 patients with stage III SCLC who underwent chemotherapy or chest radiotherapy were enrolled in this study, including 103 patients at stage IIIA and 57 patients at stage IIIB. The short-term and long-term outcomes following chemotherapy and chest radiotherapy were compared between the two groups.

Results: There was no significant difference in progression-free survival (PFS) (9.5 vs. 10.0 months, P=0.065) or overall survival (OS) (14.0 vs. 14.0 months, P=0.231) between early radiotherapy and late radiotherapy in stage IIIA SCLC. PFS in stage IIIB patients was longer in the late radiotherapy group than in early radiotherapy (11.0 vs. 9.0 months, P=0.041), but the difference in OS was not statistically significant between the two groups (14.0 vs. 17.0 months, P=0.110). There was no significant difference in short-term and long-term therapeutic effects between stages IIIA and IIIB. Patients with stage IIIB who received late radiotherapy seemed to have a survival advantage, but the difference was not statistically significant (P=0.549).

Conclusions: Treatment mode had no impact on patients at stage IIIA. Late radiotherapy showed more effectiveness for patients at stage IIIB.
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http://dx.doi.org/10.21037/apm-21-50DOI Listing
June 2021

Surface Structures of MnO and the Partition of Oxidation States of Mn.

J Phys Chem Lett 2021 Jun 11:5675-5681. Epub 2021 Jun 11.

National Center for Electron Microscopy in Beijing, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, P. R. China.

The Mn(III) ions at MnO surface are hypothesized to contribute to catalytic activity in oxygen reduction reaction. However, the surface structure and stability of MnO are far less understood. Here, the atomic structures of the widespread (101) and (001) surfaces of MnO are determined by combining aberration-corrected transmission electron microscopy and DFT calculations. The surface stabilization mechanisms and the oxidation states of Mn are revealed and correlated to the catalytic activity of the surfaces. The results show that the (101) surface undergoes a subsurface reconstruction, forming a rock-salt-type surface layer. The Mn(III) ions are in the outermost layer of the (001) surface but in the subsurface of the (101) surface. The surface partition of the Mn(III) ions provides a microscopic understanding to the observed higher catalytic activity of the (001) surface relative to the (101) surface and would contribute to further development of novel catalysts based on MnO.
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http://dx.doi.org/10.1021/acs.jpclett.1c01422DOI Listing
June 2021

Methylome profiling identifies TCHH methylation in CfDNA as a noninvasive marker of liver metastasis in colorectal cancer.

FASEB J 2021 Jul;35(7):e21720

Division of General Surgery, Peking University First Hospital, Beijing, China.

Methylation of circulating free DNA (CfDNA) has emerged as an efficient marker of tumor screening and prognostics. However, no efficient methylation marker has been developed for monitoring liver metastasis (LM) in colorectal cancer (CRC). Utilizing methylome profiling and bisulfite sequencing polymerase chain reaction of paired primary and LM sites, significantly increased methylation of TCHH was identified in the process of LM in CRC in the present study. Methylight analysis of TCHH methylation in CfDNA displayed a promisingly discriminative power between CRC with and without LM. Besides, significant coefficient of TCHH methylation and LM tumor volume was also validated. Together, these results indicated the potential of TCHH methylation in CfDNA as a monitoring marker of LM in CRC.
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http://dx.doi.org/10.1096/fj.202100266RDOI Listing
July 2021

Contribution of Growth Arrest-Specific 5/miR-674 to the Hypothalamus Pituitary Adrenal Axis Regulation Effect by Electroacupuncture following Trauma.

Neuroimmunomodulation 2021 Jun 7:1-13. Epub 2021 Jun 7.

Department of Orthopedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.

Background: Electroacupuncture (EA) can improve trauma-induced hypothalamus pituitary adrenal axis (HPA) hyperactivity. However, the mechanism underlying the EA effect has not been fully understood.

Methods And Study Design: This study was undertaken to explore the role of hypothalamic growth arrest-specific 5 (Gas5) in the regulation of EA on HPA axis function post-surgery. Paraventricular nuclear Gas5 levels were upregulated in rats using an intracerebroventricular injection of pAAV-Gas5. Primary hypothalamic neurons and 293T cells were cultured for miRNA and siRNAs detection. Radioimmunoassay, PCR, Western blot, and immunohistochemistry were used for HPA axis function evaluation.

Results: The overexpression of Gas5 abolished the effect of EA on the regulation of trauma-induced HPA axis hyperactivity. Using a bioinformatics analysis and dual luciferase assay, we determined that miRNA-674 was a target of Gas5. Additionally, miRNA-674 levels were found to have decreased in trauma rats, and this effect was reversed after EA intervention. TargetScan analysis showed that serum and glucocorticoid inducible kinase 1 (SGK1) were targets of miR-674. Moreover, we found that SGK1 protein levels increased in trauma rats and SGK1 expression inhibition alleviated HPA axis abnormality post-surgery. EA could improve the number of hypothalamus iba-1 positive cells and hypothalamic interleukin 1 beta protein expression.

Conclusions: Our study demonstrated the involvement of the hypothalamic Gas5/miRNA-674/SGK1 signaling pathway in EA regulation of HPA axis function after trauma.
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http://dx.doi.org/10.1159/000513385DOI Listing
June 2021

Swi6B, an alternative splicing isoform of Swi6, mediates the cell wall integrity of Ganoderma lucidum.

Environ Microbiol 2021 Jun 7. Epub 2021 Jun 7.

Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture, Microbiology Department, College of Life Sciences, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China.

The cell wall integrity (CWI) signaling activates the transcription factor Swi6 through a MAPK signaling cascade in response to cell wall stresses. In this study, we observed two different mRNA variants of swi6 (GlSwi6A and GlSwi6B) existed, due to alternative splicing. Besides, the expression level of GlSwi6B was higher than that of the GlSwi6A mRNA variant. The co-silencing of GlSwi6A and GlSwi6B was more sensitive to cell wall stress compared with WT, resulting in a decrease of 78% and 76% in chitin and β-1,3-d-glucan content respectively. However, only the overexpression of GlSwi6B decreased the sensitivity to cell wall stress and increased the content of chitin and β-1,3-d-glucan compared with the WT strain. Furthermore, Y1H, EMSA and BLI assays revealed that the GlSwi6B could bind to the promoters of chitin and glucan synthesis genes (GL24454 and GL18134). However, the binding phenome has not been observed in the isoform GlSwi6A. Taken together, our results found two different transcripts generated from Swi6, in which the alternative splice isoform of GlSwi6B participates in regulating the CWI of G. lucidum. This study provides the first insight into the alternative splicing isoform of GlSwi6B in the regulation of CWI signaling in fungi.
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http://dx.doi.org/10.1111/1462-2920.15627DOI Listing
June 2021

Single-cell transcriptomic analysis reveals a hepatic stellate cell-activation roadmap and myofibroblast origin during liver fibrosis.

Hepatology 2021 Jun 5. Epub 2021 Jun 5.

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.

Hepatic stellate cells (HSCs) and portal fibroblasts (PFs) are the major sources of collagen-producing myofibroblasts during liver fibrosis, depending on different etiologies. However, the mechanisms by which their dynamic gene expression directs the transition from the quiescent to the activated state-as well as their contributions to fibrotic myofibroblasts-remain unclear. Here, we analyze the activation of HSCs and PFs in CCL - and bile duct ligation (BDL)-induced fibrosis mouse models, using single-cell RNA-sequencing and lineage tracing. We demonstrate that HSCs, rather than PFs, undergo dramatic transcriptomic changes, with the sequential activation of inflammatory, migrative, and ECM-producing programs. The data also reveal that HSCs are the exclusive source of myofibroblasts in CCL -treated liver, while PFs are the major source of myofibroblasts in early cholestatic liver fibrosis. Single-cell and lineage-tracing analysis also uncovers differential gene expression features between HSCs and PFs; for example, nitric oxide (NO) receptor soluble guanylate cyclase (sGC) is exclusively expressed in HSCs, but not in PFs. The sGC stimulator Riociguat potently reduced liver fibrosis in CCL -treated livers but showed no therapeutic efficacy in BDL livers. This study provides a transcriptional roadmap for the activation of HSCs during liver fibrosis and yields comprehensive evidence that the differential transcriptomic features of HSCs and PFs, along with their relative contributions to liver fibrosis of different etiologies, should be considered in developing effective anti-fibrotic therapeutic strategies.
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http://dx.doi.org/10.1002/hep.31987DOI Listing
June 2021

Membrane recruitment of Atg8 by Hfl1 facilitates turnover of vacuolar membrane proteins in yeast cells approaching stationary phase.

BMC Biol 2021 Jun 4;19(1):117. Epub 2021 Jun 4.

State Key Laboratory of Microbial Metabolism and Joint International Research Laboratory of Metabolic & Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China.

Background: The vacuole/lysosome is the final destination of autophagic pathways, but can also itself be degraded in whole or in part by selective macroautophagic or microautophagic processes. Diverse molecular mechanisms are involved in these processes, the characterization of which has lagged behind those of ATG-dependent macroautophagy and ESCRT-dependent endosomal multivesicular body pathways.

Results: Here we show that as yeast cells gradually exhaust available nutrients and approach stationary phase, multiple vacuolar integral membrane proteins with unrelated functions are degraded in the vacuolar lumen. This degradation depends on the ESCRT machinery, but does not strictly require ubiquitination of cargos or trafficking of cargos out of the vacuole. It is also temporally and mechanistically distinct from NPC-dependent microlipophagy. The turnover is facilitated by Atg8, an exception among autophagy proteins, and an Atg8-interacting vacuolar membrane protein, Hfl1. Lack of Atg8 or Hfl1 led to the accumulation of enlarged lumenal membrane structures in the vacuole. We further show that a key function of Hfl1 is the membrane recruitment of Atg8. In the presence of Hfl1, lipidation of Atg8 is not required for efficient cargo turnover. The need for Hfl1 can be partially bypassed by blocking Atg8 delipidation.

Conclusions: Our data reveal a vacuolar membrane protein degradation process with a unique dependence on vacuole-associated Atg8 downstream of ESCRTs, and we identify a specific role of Hfl1, a protein conserved from yeast to plants and animals, in membrane targeting of Atg8.
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http://dx.doi.org/10.1186/s12915-021-01048-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176713PMC
June 2021

Facile strategy to prepare polyimide nanofiber assembled aerogel for effective airborne particles filtration.

J Hazard Mater 2021 Aug 24;415:125739. Epub 2021 Mar 24.

College of Materials Science and Engineering, Donghua University, Shanghai 201620, People's Republic of China; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Donghua University, Shanghai 201620, People's Republic of China. Electronic address:

Polyimide nanofiber (PINF) aerogel materials have received extensive attention as heat insulation, sensors and filtration media due to their excellent thermodynamic properties and unique porous structure. However, PINF must be difficult to disperse in organic solvents (dioxane or dimethyl sulfoxide) and dimensional instability has been regarded as issues that limits the preparation of PINF aerogels, especially in the water. So, it is of great significance to prepare polyimide aerogels with stable structure using water as a dispersant. In this work, the electrospun polyimide nanofiber precursor (polyamic acid (PAA) nanofiber (PAANF)) is uniformly dispersed in water, and triethylamine is added to terminated PAA oligomer as a binder. The resultant PINF aerogel has excellent mechanical properties with outstanding elasticity and a maximum compressive stress of 7.03 kpa at 50% strain. Furthermore, due to the extremely high porosity (98.4%) and hierarchical porous structure, the aerogel exhibits a high filtration efficiency (99.83%) for PM2.5, while the pressure drop is lower than that of the corresponding nanofiber membrane materials, which will facilitate its application in high temperature filtration and other fields.
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http://dx.doi.org/10.1016/j.jhazmat.2021.125739DOI Listing
August 2021

Thymic stromal lymphopoietin participates in the TLR2-and TLR4-dependent immune response triggered by Aspergillus fumigatus in human corneal cells.

Exp Eye Res 2021 May 31;209:108644. Epub 2021 May 31.

Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, 250012, PR China. Electronic address:

Fungal keratitis constitutes a serious vision-threatening disease. Toll-like receptors (TLRs) comprise key mediators of innate immunity triggered by Aspergillus fumigatus (AF) in the cornea, but the messenger between innate and adaptive immunity remained unknown. Thymic stromal lymphopoietin (TSLP) represents a critical factor of adaptive immunity. Here we investigated the expression of TSLP in corneal epithelial and stromal cells challenged by AF and its relationship with TLRs. We stimulated corneal cells with TLR ligands zymosan or lipopolysaccharide (LPS), human recombinant TSLP, or AF hyphae for various periods, with or without prior TLR2, TLR4, or TSLP inhibition. TLR2, TLR4, TSLP, IL-8, and TNF-α release and expression were measured via enzyme-linked immunosorbent analysis, quantitative polymerase chain reaction, or western blot. Corneal cell stimulation with zymosan or LPS induced up-regulated TSLP expression. Enhanced TSLP expression was associated with AF treatment in human corneal cells; TLR2 or TLR4 inhibition impaired the AF-induced TSLP levels. Human recombinant TSLP augmented TLR2 and TLR4 expression; RNA interference of TSLP attenuated TLR, IL-8, and TNF-α expression stimulated by AF hyphae. These findings indicated that TSLP participates in the immune response of corneal cells triggered by AF, which is closely related to TLR function, and the innate immunity mediated by TLRs could be enhanced by TSLP. Innate immunity may therefore transmit inflammatory signals to adaptive immunity through activation of TSLP; in turn, adaptive immunity likely exerts certain regulatory effects on innate immunity via TSLP. That is, TSLP could interact with innate immunity mediated by TLR2 and TLR4 in human corneal cells challenged by AF and thus may serve as a messenger between the innate and adaptive immune responses in AF keratitis.
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http://dx.doi.org/10.1016/j.exer.2021.108644DOI Listing
May 2021

Effect of Ionizing Radiation on the Bacterial and Fungal Endophytes of the Halophytic Plant .

Microorganisms 2021 May 13;9(5). Epub 2021 May 13.

State Key Laboratory of Agrobiotechnology and Key Laboratory of Soil Microbiology, Ministry of Agriculture, College of Biological Sciences, China Agricultural University, Beijing 100193, China.

Endophytic bacteria and fungi colonize plants that grow in various types of terrestrial and aquatic ecosystems. Our study investigates the communities of endophytic bacteria and fungi of halophyte growing in stressed habitats with ionizing radiation. The geochemical factors and radiation (at low, medium, high level and control) both affected the structure of endophytic communities. The bacterial class Actinobacteria and the fungal class Dothideomycetes predominated the endophytic communities of . Aerial tissues of had higher fungal diversity, while roots had higher bacterial diversity. Radiation had no significant effect on the abundance of bacterial classes. Soil pH, total nitrogen, and organic matter showed significant effects on the diversity of root endophytes. Radiation affected bacterial and fungal community structure in roots but not in aerial tissues, and had a strong effect on fungal co-occurrence networks. Overall, the genetic diversity of both endophytic bacteria and fungi was higher in radioactive environments, however negative correlations were found between endophytic bacteria and fungi in the plant. The genetic diversity of both endophytic bacteria and fungi was higher in radioactive environments. Our findings suggest that radiation affects root endophytes, and that the endophytes associated with aerial tissues and roots of follow different mechanisms for community assembly and different paradigms in stress response.
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http://dx.doi.org/10.3390/microorganisms9051050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152737PMC
May 2021

NAD+ deficiency and mitochondrial dysfunction in granulosa cells of women with polycystic ovary syndrome‡.

Biol Reprod 2021 May 29. Epub 2021 May 29.

Center for Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Polycystic ovary syndrome (PCOS) is a prevalent heterogeneous endocrine disorder characterized by ovulation dysfunction, androgen excess, ovarian polycystic changes, insulin resistance, and infertility. Although underlying mechanisms for PCOS are still unknown, inflammation and mitochondrial dysfunction in granulosa cells (GCs) of PCOS patients have been reported. Here, we found that Nicotinamide Adenine Dinucleotide (NAD+) levels in GCs of PCOS patients was significantly decreased when compared with controls. Also, we found that higher expression of inflammation factors, increased reactive oxygen species (ROS) accumulation, lower adenosine triphosphate (ATP) generation, and decreased mitochondrial membrane potential, as well as abnormal mitochondrial dynamics in GCs of PCOS patients. In addition, the NAD+ levels were decreased after activation of inflammation in human granulosa-like tumor cell line (KGN) treated by Lipopolysaccharide (LPS). However, supplementation of nicotinamide riboside (NR), a NAD+ precursor, could largely restore the NAD+ content, reduce ROS levels and improve mitochondrial function demonstrated by increased mitochondrial membrane potential and ATP generation in LPS-treated KGN cells. Our data suggested that inflammation decreased NAD+ levels in GCs of PCOS patients, while supplementation of NR could restore NAD+ levels and alleviated mitochondrial dysfunction in GCs of PCOS patients.
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http://dx.doi.org/10.1093/biolre/ioab078DOI Listing
May 2021

Long-Term Observation and Sequencing Analysis of SKPs-Derived Corneal Endothelial Cell-Like Cells for Treating Corneal Endothelial Dysfunction.

Cell Transplant 2021 Jan-Dec;30:9636897211017830

Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong, China.

Corneal endothelial dysfunction is a principal cause of visual deficiency. Corneal transplantation is the most effective treatment for corneal endothelial dysfunction. However, a severe shortage of available donor corneas or human corneal endothelial cells (HCECs) remains a global challenge. Previously, we acquired corneal endothelial cell-like cells (CEC-like cells) derived from human skin-derived precursors (SKPs). CEC-like cells were injected into rabbit and monkey corneal endothelial dysfunction models and exerted excellent therapeutic effect. In this study, we prolonged the clinical observation in the monkey experiment for 2 years. Polymerase chain reaction (PCR) and DNA sequencing were carried out to confirm the existence of CEC-like cells. Histological examinations were carried out to show the corneal morphology. Further transcriptome sequencing was also carried out on HCEC, CEC-like cells before transplantation and after transplantation. We found that the monkeys cornea remained transparent and normal thickness. The total endothelial cell density decreased gradually, but tended to be stable and remained in a normal range during 2-year observation. The CEC-like cells persist during observation and could adapt to the microenvironment after transplantation. The gene expression pattern of CEC-like cells was similar to HCEC and changed slightly after transplantation. In conclusion, this study presented a brand-new insight into CEC-like cells and further provided a promising prospect of cell-based therapy for corneal endothelial dysfunction. The renewable cell source, novel derivation method and simple treatment strategy may be clinically applied in regenerative medicine in the future.
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http://dx.doi.org/10.1177/09636897211017830DOI Listing
May 2021

Orexin A improves the cognitive impairment induced by chronic intermittent hypoxia in mice.

Brain Res Bull 2021 Aug 27;173:203-210. Epub 2021 May 27.

Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, China. Electronic address:

The orexin neuron in lateral hypothalamus (LH) was involved in the regulation of sleep-wake cycle. However, the effect of orexin A (OXA) on cognitive impairment resulting from diverse diseases remains controversial. In this study, we investigated the effect of OXA on cognitive impairment induced by chronic intermittent hypoxia (CIH) in mice. Adult (10 weeks old) male C57BL/6 mice were randomly divided into the following four groups: normoxia control (NC)+normal saline (NS), NC + OXA, CIH + NS and CIH + OXA group. Following the CIH mice models establishment, OXA was injected into the right lateral ventricles of mice by a micro-injection system. Water maze test was used to assess spatial memory abilities of the mice. The expression of OXA and c-Fos in LH were analyzed by immunofluorescence staining. Apoptotic cell death and oxidative stress in hippocampus were evaluated using multiple methods including TUNEL, western blot and biochemical analysis. Behavioral tests revealed that CIH significantly increased the escape latency and time of arriving platform, of which were markedly decreased by OXA treatment. Similarly, the CIH + NS group was worse than NC + NS group in terms of the number of platform crossing and time in the target quadrant, of which were also significantly improved by OXA treatment. The number of OXA + neuron in LH was decreased, but the percentage of c-Fos+/OXA + neuron in LH was remarkably increased by CIH. Furthermore, we found that micro-injection of OXA attenuated CIH-induced apoptotic cell death and oxidative stress in the hippocampus. Our results suggested that OXA might improve cognitive impairment induced by CIH through inhibiting hippocampal apoptosis and oxidative stress.
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http://dx.doi.org/10.1016/j.brainresbull.2021.05.022DOI Listing
August 2021

Functions and Targets of miR-335 in Cancer.

Onco Targets Ther 2021 20;14:3335-3349. Epub 2021 May 20.

Department of Oncology, The Affiliated Jiangning Hospital with Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.

MicroRNAs (miRNAs) are small non-coding RNAs (18~25 nt in length) that act as master regulators of eukaryotic gene expression. They might play an oncogenic or tumor-suppressive role in multiple cancers. In recent decades, several studies have focused on the functions and mechanisms of miR-335 in cancer. The expression level of miR-335 in tissues and cells varies with cancer types, and miR-335 has been proposed as a potential biomarker for the prognosis of cancer. Besides, miR-335 may serve as an oncogene or tumor suppressor via regulating different targets or pathways in tumor initiation, development, and metastasis. Furthermore, miR-335 also influences tumor microenvironment and drug sensitivity. MiR-335 is regulated by various factors such as lncRNAs and microRNAs. In this review, we reveal the functions and targets of miR-335 in various cancers and its potential application as a possible biomarker in prognostic judgment and treatment of malignant tumors.
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http://dx.doi.org/10.2147/OTT.S305098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144171PMC
May 2021

Ethoxyquin is neuroprotective and partially prevents somatic and autonomic neuropathy in db/db mouse model of type 2 diabetes.

Sci Rep 2021 May 24;11(1):10749. Epub 2021 May 24.

Departments of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Ethoxyquin (EQ), a quinolone-based antioxidant, has demonstrated neuroprotective properties against several neurotoxic drugs in a phenotypic screening and is shown to protect axons in animal models of chemotherapy-induced peripheral neuropathy. We assessed the effects of EQ on peripheral nerve function in the db/db mouse model of type II diabetes. After a 7 week treatment period, 12-week-old db/db-vehicle, db/+ -vehicle and db/db-EQ treated animals were evaluated by nerve conduction, paw withdrawal against a hotplate, and fiber density in hindlimb footpads. We found that the EQ group had shorter paw withdrawal latency compared to vehicle db/db group. The EQ group scored higher in nerve conduction studies, compared to vehicle-treated db/db group. Morphology studies yielded similar results. To investigate the potential role of mitochondrial DNA (mtDNA) deletions in the observed effects of EQ, we measured total mtDNA deletion burden in the distal sciatic nerve. We observed an increase in total mtDNA deletion burden in vehicle-treated db/db mice compared to db/+ mice that was partially prevented in db/db-EQ treated animals. These results suggest that EQ treatment may exert a neuroprotective effect in diabetic neuropathy. The prevention of diabetes-induced mtDNA deletions may be a potential mechanism of the neuroprotective effects of EQ in diabetic neuropathy.
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http://dx.doi.org/10.1038/s41598-021-89781-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144207PMC
May 2021

Weighted Gene Co-expression Network Analysis Identifies CALD1 as a Biomarker Related to M2 Macrophages Infiltration in Stage III and IV Mismatch Repair-Proficient Colorectal Carcinoma.

Front Mol Biosci 2021 29;8:649363. Epub 2021 Apr 29.

Department of General Surgery, Peking University First Hospital, Beijing, China.

Immunotherapy has achieved efficacy for advanced colorectal cancer (CRC) patients with a mismatch-repair-deficient (dMMR) subtype. However, little immunotherapy efficacy was observed in patients with the mismatch repair-proficient (pMMR) subtype, and hence, identifying new immune therapeutic targets is imperative for those patients. In this study, transcriptome data of stage III/IV CRC patients were retrieved from the Gene Expression Omnibus database. The CIBERSORT algorithm was used to quantify immune cellular compositions, and the results revealed that M2 macrophage fractions were higher in pMMR patients as compared with those with the dMMR subtype; moreover, pMMR patients with higher M2 macrophage fractions experienced shorter overall survival (OS). Subsequently, weighted gene co-expression network analysis and protein-protein interaction network analysis identified six hub genes related to M2 macrophage infiltrations in pMMR CRC patients: , , , , , and . Univariate and multivariate Cox regression analyses then determined as the independent prognostic biomarker for OS. was upregulated specifically the in CMS4 CRC subtype, and single-sample Gene Set Enrichment Analysis (ssGSEA) revealed that was significantly correlated with angiogenesis and TGF-β signaling gene sets enrichment scores in stage III/IV pMMR CRC samples. The Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm and correlation analysis revealed that was significantly associated with multiple immune and stromal components in a tumor microenvironment. In addition, GSEA demonstrated that high expression of was significantly correlated with antigen processing and presentation, chemokine signaling, leukocyte transendothelial migration, vascular smooth muscle contraction, cytokine-cytokine receptor interaction, cell adhesion molecules, focal adhesion, MAPK, and TGF-beta signaling pathways. Furthermore, the proliferation, invasion, and migration abilities of cancer cells were suppressed after reducing expression in CRC cell lines. Taken together, multiple bioinformatics analyses and cell-level assays demonstrated that could serve as a prognostic biomarker and a prospective therapeutic target for stage III/IV pMMR CRCs.
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http://dx.doi.org/10.3389/fmolb.2021.649363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116739PMC
April 2021

How Aconiti Radix Cocta can Treat Gouty Arthritis Based on Systematic Pharmacology and UPLC-QTOF-MS/MS.

Front Pharmacol 2021 30;12:618844. Epub 2021 Apr 30.

Pharmacy College, Jiangxi University of Traditional Chinese Medicine, Nanchang, China.

Gouty arthritis (GA) is a common metabolic disease caused by a long-term disorder of purine metabolism and increased serum levels of uric acid. The processed product of dried root of Debeaux ( cocta, ARC) is used often in traditional Chinese medicine (TCM) to treat GA, but its specific active components and mechanism of action are not clear. First, we used ultra-performance liquid chromatography-quadrupole/time-of-flight tandem mass spectrometry to identify the chemical spectrum of ARC. Based on this result, we explored the active components of ARC in GA treatment and their potential targets and pathways. Simultaneously, we used computer simulations, cell experiments and animal experiments to verify the prediction results of systems pharmacology. , we used aurantiamide acetate (AA) to treat monosodium urate (MSU)-stimulated THP-1 cells and demonstrated the reliability of the prediction by western blotting and real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). ELISAs kit were used to measure changes in levels of proinflammatory factors in rats with GA induced by MSU to demonstrate the efficacy of ARC in GA treatment. Forty-three chemical constituents in ARC were identified. ARC could regulate 65 targets through 29 active components, and then treat GA, which involved 1427 Gene Ontology (GO) terms and 146 signaling pathways. Signaling pathways such as proteoglycans in cancer, C-type lectin receptor signaling pathway, and TNF signaling pathway may have an important role in GA treatment with ARC. results showed that the active components songoramine and ignavine had high binding to mitogen-activated protein kinase p38 alpha (MAPK14) and matrix metallopeptidase (MMP)9, indicating that ARC treatment of GA was through multiple components and multiple targets. experiments showed that AA in ARC could effectively reduce expression of MAPK14, MMP9, and cyclooxygenase2 (PTGS2) in THP-1 cells stimulated by MSU, whereas it could significantly inhibit the mRNA expression of Caspase-1, spleen tyrosine kinase (SYK), and PTGS2. Animal experiments showed that a ARC aqueous extract could significantly reduce expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and intereleukin (IL)-18 in the serum of GA rats stimulated by MSU. Hence, ARC may inhibit inflammation by regulating the proteoglycans in cancer-associated signaling pathways. ARC treatment of GA may have the following mechanisms, ARC can reduce MSU crystal-induced joint swelling, reduce synovial tissue damage, and reduce the expression of inflammatory factors in serum. AA in ARC may inhibit inflammation by regulating the protein expression of MAPK14, MMP9, and PTGS2 and the mRNA expression of caspase-1, SYK, and PTGS2.
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http://dx.doi.org/10.3389/fphar.2021.618844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121251PMC
April 2021

New Insights into the Quantitative Relationship between Surface Chemistry of Fullerene (C60) and Solubility Parameters and Compatibility with Polymers.

J Phys Chem B 2021 05 12;125(20):5420-5433. Epub 2021 May 12.

College of Science, Nanjing Forestry University, Nanjing 210037, China.

The quantitative relationship between the surface chemistry of carbon materials and the compatibility with polymers is a fundamental and vital physical chemistry problem in the field of polymer nanocomposites. Traditional experimental methods are difficult to solve this problem, so no theory has been formed to guide the functionalization of carbon materials. In this work, the quantitative relationship between functional groups and Hildebrand (δ) and transformed Hansen (δ and δ) solubility parameters of fullerene (C60) was determined by molecular dynamics simulation. Besides, which solubility parameter can more accurately predict the compatibility between C60 and three typical polymers with different polarity as a function of grafting ratio is investigated. Very interestingly, no matter which group is grafted, δ and δ of C60 show a slight increase first and then a decrease with the grafting ratio, whereas δ first increases abruptly and then decreases slightly. The introduction of polar groups (-OH, -COOH, and -NH) is conducive to improving the compatibility between C60 and polymers, whereas the introduction of the nonpolar group (-CH) is not. In terms of predicting compatibility, the Hildebrand solubility parameter is better than the Hansen solubility parameter due to the nonpolar nature of the polymers, even for nitrile butadiene rubber. Finally, the optimum grafting ratios corresponding to the maximum binding energies of C60/polymers mixtures were obtained. This study provides a new understanding of the functionalization of C60 at the molecular level and promotes the development of the theory of the thermodynamics of mixing.
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http://dx.doi.org/10.1021/acs.jpcb.1c01969DOI Listing
May 2021

Atomic-scale insights into quantum-order parameters in bismuth-doped iron garnet.

Proc Natl Acad Sci U S A 2021 May;118(20)

National Center for Electron Microscopy in Beijing, School of Materials Science and Engineering, Tsinghua University, 100084 Beijing, People's Republic of China;

Bismuth and rare earth elements have been identified as effective substituent elements in the iron garnet structure, allowing an enhancement in magneto-optical response by several orders of magnitude in the visible and near-infrared region. Various mechanisms have been proposed to account for such enhancement, but testing of these ideas is hampered by a lack of suitable experimental data, where information is required not only regarding the lattice sites where substituent atoms are located but also how these atoms affect various order parameters. Here, we show for a Bi-substituted lutetium iron garnet how a suite of advanced electron microscopy techniques, combined with theoretical calculations, can be used to determine the interactions between a range of quantum-order parameters, including lattice, charge, spin, orbital, and crystal field splitting energy. In particular, we determine how the Bi distribution results in lattice distortions that are coupled with changes in electronic structure at certain lattice sites. These results reveal that these lattice distortions result in a decrease in the crystal-field splitting energies at Fe sites and in a lifted orbital degeneracy at octahedral sites, while the antiferromagnetic spin order remains preserved, thereby contributing to enhanced magneto-optical response in bismuth-substituted iron garnet. The combination of subangstrom imaging techniques and atomic-scale spectroscopy opens up possibilities for revealing insights into hidden coupling effects between multiple quantum-order parameters, thereby further guiding research and development for a wide range of complex functional materials.
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http://dx.doi.org/10.1073/pnas.2101106118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157958PMC
May 2021

G2 and S phase-expressed-1 acts as a putative tumor promoter in cervical cancer by enhancing Wnt/β-catenin signaling via modulation of GSK-3β.

Environ Toxicol 2021 May 11. Epub 2021 May 11.

Department of Physiology and Pathophysiology, Air Force Medical University, Xi'an, China.

G2 and S phase-expressed-1 (GTSE1) is currently identified as a key regulator of carcinogenesis. However, the involvement of GTSE1 in cervical cancer is unclear. The aims of this work were to explore the relationship between GTSE1 and cervical cancer. Our data elucidated high GTSE1 expression in cervical cancer tissue, which predicted a poor prognosis in cervical cancer patients. GTSE1 knockdown had tumor-suppressive effects in cervical cancer cells by inhibiting cell proliferative and invasive abilities. GTSE1 knockdown decreased the level of phosphorylated glycogen synthase kinase-3β (GSK-3β) and active β-catenin, resulted in inactivation of Wnt/β-catenin signaling. Suppression of GSK-3β remarkably abolished the GTSE1-knockdown-induced inhibitory effects on Wnt/β-catenin signaling. Suppression of Wnt/β-catenin signaling abolished the GTSE1-overexpression-induced oncogenic effects. Notably, GTSE1 knockdown impeded the in vivo tumorigenicity of cervical cancer cells. In short, this work demonstrates that GTSE1 is overexpressed in cervical cancer and GTSE1 suppression exerts a tumor-inhibiting role in cervical cancer by down-regulating Wnt/β-catenin signaling. Our work underlines a crucial relevance between GTSE1 and cervical cancer progression and suggests GTSE1 as a promising therapeutic target for cervical cancer.
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http://dx.doi.org/10.1002/tox.23158DOI Listing
May 2021

Preeclampsia Prevalence, Risk Factors, and Pregnancy Outcomes in Sweden and China.

JAMA Netw Open 2021 May 3;4(5):e218401. Epub 2021 May 3.

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.

Importance: Preeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. Within-country studies have reported racial differences in the presentation and outcome, but little is known about differences between countries.

Objective: To compare preeclampsia prevalence, risk factors, and pregnancy outcomes between the Swedish and Chinese populations.

Design, Setting, And Participants: This cross-sectional study compared deliveries from the Swedish national Medical Birth Register (2007-2012) and the China Labor and Delivery Survey (2015-2016). The Swedish Medical Birth Register records maternal, pregnancy, and neonatal information for nearly all deliveries in Sweden. The China Labor and Delivery Survey was conducted throughout China, and these data were reweighted to enable national comparisons. Participants included 555 446 deliveries from Sweden and 79 243 deliveries from China. Data management and analysis was conducted from November 2018 to August 2020 and revised in February to March 2021.

Exposures: Maternal characteristics, parity, multiple gestation, chronic and gestational diabetes, cesarean delivery.

Main Outcomes And Measures: Preeclampsia prevalence and risk factors, overall and for mild and severe forms and rates of adverse neonatal outcomes compared with pregnancies with no gestational hypertension.

Results: The 555 446 Swedish pregnancies and 79 243 Chinese pregnancies had mean (SD) maternal age of 30.9 (5.3) years and 28.6 (4.6) years, respectively. The overall prevalence of preeclampsia was similar in Sweden and China, 16 068 (2.9%) and 1803 (2.3%), respectively, but with 5222 cases (32.5%) considered severe in Sweden and 1228 cases (68.1%) considered severe in China. Obesity (defined as BMI ≥28 in China and BMI ≥30 in Sweden) was a stronger risk factor in China compared with Sweden (China: odds ratio [OR], 5.12; 95% CI, 3.82-6.86; Sweden: OR, 3.49; 95% CI, 3.31-3.67). Nulliparity had a much stronger association with severe preeclampsia in Sweden compared with China (Sweden: OR, 3.91; 95% CI, 3.65-4.18; China: OR, 1.65; 95% CI, 1.20-2.25). The overall stillbirth rate for singleton in China was more than 3-fold higher than in Sweden (846/77 512[1.1%] vs 1753/547 219 [0.3%], P < .001), and 10-fold higher among women with preeclampsia (66/1652 [4.6%] vs 60/14 499[0.4%], P < .001).

Conclusions And Relevance: In this study, the prevalence rates of preeclampsia in Sweden and China were similar, but women in China had more severe disease and worse pregnancy outcomes than women in Sweden. The associations of obesity and nulliparity with preeclampsia suggest a role for lifestyle and health care factors but may reflect some differences in pathophysiology. These findings have relevance for current efforts to identify high-risk pregnancies and early serum markers because the value of risk prediction models and biomarkers may be population specific.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.8401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111481PMC
May 2021

Targeted resequencing showing novel common and rare genetic variants increases the risk of asthma in the Chinese Han population.

J Clin Lab Anal 2021 Jun 9;35(6):e23813. Epub 2021 May 9.

Division of Cardiology, Departments of Internal Medicine and Genetic Diagnosis Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Although studies have identified hundreds of genetic variants associated with asthma risk, a large fraction of heritability remains unexplained, especially in Chinese individuals.

Methods: To identify genetic risk factors for asthma in a Han Chinese population, 211 asthma-related genes were first selected based on database searches. The genes were then sequenced for subjects in a Discovery Cohort (284 asthma patients and 205 older healthy controls) using targeted next-generation sequencing. Bioinformatics analysis and statistical association analyses were performed to reveal the associations between rare/common variants and asthma, respectively. The identified common risk variants underwent a validation analysis using a Replication Cohort (664 patients and 650 controls).

Results: First, we identified 18 potentially functional rare loss-of-function (LOF) variants in 21/284 (7.4%) of the asthma cases. Second, using burden tests, we found that the asthma group had nominally significant (p < 0.05) burdens of rare nonsynonymous variants in 10 genes. Third, 23 common single-nucleotide polymorphisms were associated with the risk of asthma, 7/23 (30.4%) and 9/23 (39.1%) of which were modestly significant (p < 9.1 × 10 ) in the Replication Cohort and Combined Cohort, respectively. According to our cumulative risk model involving the modestly associated alleles, middle- and high-risk subjects had a 2.0-fold (95% CI: 1.621-2.423, p = 2.624 × 10 ) and 6.0-fold (95% CI: 3.623-10.156, p = 7.086 × 10 ) increased risk of asthma, respectively, compared with low-risk subjects.

Conclusion: This study revealed novel rare and common genetic risk factors for asthma, and provided a cumulative risk model for asthma risk prediction and stratification in Han Chinese individuals.
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http://dx.doi.org/10.1002/jcla.23813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183914PMC
June 2021

Community structure of environmental microorganisms associated with COVID-19 affected patients.

Aerobiologia (Bologna) 2021 May 4:1-9. Epub 2021 May 4.

College of Pulmonary and Critical Care Medicine, Chinese PLA General Hospital, Beijing, 100853 China.

To clarify the characteristics and distribution of hospital environmental microbiome associated with confirmed COVID-19 patients. Environmental samples with varying degrees of contamination which were associated with confirmed COVID-19 patients were collected, including 13 aerosol samples collected near eight patients in different wards, five swabs from one patient's skin and his personal belongings, and two swabs from the surface of positive pressure respiratory protective hood and the face shield from a physician who had close contact with one patient. Metagenomic next-generation sequencing (mNGS) was used to analyze the composition of the microbiome. One of the aerosol samples (near patient 4) was detected positive for COVID-19, and others were all negative. The environmental samples collected in different wards possessed protean compositions and community structures, the dominant genera including , , , , , and . Top 10 of genera accounted for more than 76.72%. Genera abundance and proportion of human microbes and pathogens radiated outward from the patient, while the percentage of environmental microbes increased. The abundance of the pathogenic microorganism of medical supplies is significantly higher than other surface samples. The microbial compositions of the aerosol collected samples nearby the patients were mostly similar to those from the surfaces of the patient's skin and personal belongings, but the abundance varied greatly. The positive rate of COVID-19 RNA detected from aerosol around patients in general wards was quite low. The ward environment was predominantly inhabited by species closely related to admitted patients. The spread of hospital microorganisms via aerosol was influenced by the patients' activity.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10453-021-09708-5.
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http://dx.doi.org/10.1007/s10453-021-09708-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093081PMC
May 2021

Enantiomeric profiling of a chiral benzothiazole necroptosis inhibitor.

Bioorg Med Chem Lett 2021 Jul 6;43:128084. Epub 2021 May 6.

School of Pharmacy, Ningxia Medical University, 1160 Shengli Street, Yinchuan 750004, China; School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China. Electronic address:

Necroptosis is a form of programmed cell death that contributes to the pathophysiology of multiple diseases. Development of small-molecule anti-necroptosis agents has great promising clinical therapeutic relevance. The benzothiazole compounds were discovered by our group from an in-house fluorine-containing compound library as potent necroptosis inhibitors. Herein, a chiral dimethylcyclopropyl benzothiazole necroptosis inhibitor was developed and the enantiomeric profiling resulted that the (S) form was generally more potent than the (R) counterpart in 2 ~ 4-fold toward cell necroptosis, receptor-interacting protein (RIP) kinases 1 and 3. The chiral compounds could significantly inhibit the expression of the phosphorylation of RIPK1, RIPK3 and MLKL in necroptotic cells. The molecular modelling studies predicted the binding modes of the enantiomers with RIP and explained their activity differences, guiding further rational design of the chiral necroptosis inhibitors.
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http://dx.doi.org/10.1016/j.bmcl.2021.128084DOI Listing
July 2021

GCN4 regulates secondary metabolism through activating antioxidant genes expression under nitrogen limitation in .

Appl Environ Microbiol 2021 May 7. Epub 2021 May 7.

Key Laboratory of Agricultural Environmental Microbiology, Ministry of Agriculture; Microbiology Department, College of Life Sciences, Agricultural University, Jiangsu, Nanjing 210095, People's Republic of China.

Nitrogen limitation has been widely reported to affect the growth and development of fungi, and the transcription factor GCN4 (general control nonderepressible 4) is involved in nitrogen restriction. Here, we found that nitrogen limitation highly induced the expression of GCN4 and promoted the synthesis of ganoderic acid (GA), an important secondary metabolite in The activated GCN4 is involved in regulating GA biosynthesis. Besides, the accumulation of ROS is also affecting the synthesis of GA under nitrogen restrictions. The silencing of the gene led to further accumulation of ROS and increased the content of GA. Further studies found that GCN4 activated the transcription of antioxidant enzyme biosynthesis genes , , and (encoding glutathione reductase, glutathione-s-transferase, and catalase, respectively) through direct binding to the promoter of these genes to reduce the ROS accumulation. In conclusion, our study found that GCN4 directly interacts with the ROS signaling pathway to negatively regulate GA biosynthesis under nitrogen-limiting conditions. This provides an essential insight into the understanding of GCN4 transcriptional regulation of the ROS signaling pathway and enriches the knowledge of nitrogen regulation mechanisms in fungal secondary metabolism of Nitrogen has been widely reported to regulate secondary metabolism in fungi. Our study assesses the specific nitrogen regulatory mechanisms in We found that GCN4 directly interacts with the ROS signaling pathway to negatively regulate GA biosynthesis under nitrogen-limiting conditions. Our research highlights a novel insight that GCN4, the nitrogen utilization regulator, participates in secondary metabolism through ROS signal regulation. Besides, this also provides a theoretical foundation for exploring the regulation of other physiological processes by GCN4 through ROS in fungi.
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http://dx.doi.org/10.1128/AEM.00156-21DOI Listing
May 2021

PINK1 contained in huMSC-derived exosomes prevents cardiomyocyte mitochondrial calcium overload in sepsis via recovery of mitochondrial Ca efflux.

Stem Cell Res Ther 2021 May 6;12(1):269. Epub 2021 May 6.

Chongqing Key Laboratory of Pediatrics, Chongqing, People's Republic of China.

Background: Sepsis is a systemic inflammatory response to a local severe infection that may lead to multiple organ failure and death. Previous studies have shown that 40-50% of patients with sepsis have diverse myocardial injuries and 70 to 90% mortality rates compared to 20% mortality in patients with sepsis without myocardial injury. Therefore, uncovering the mechanism of sepsis-induced myocardial injury and finding a target-based treatment are immensely important.

Objective: The present study elucidated the mechanism of sepsis-induced myocardial injury and examined the value of human umbilical cord mesenchymal stem cells (huMSCs) for protecting cardiac function in sepsis.

Methods: We used cecal ligation and puncture (CLP) to induce sepsis in mice and detect myocardial injury and cardiac function using serological markers and echocardiography. Cardiomyocyte apoptosis and heart tissue ultrastructure were detected using TdT-mediated dUTP Nick-End Labeling (TUNEL) and transmission electron microscopy (TEM), respectively. Fura-2 AM was used to monitor Ca uptake and efflux in mitochondria. FQ-PCR and Western blotting detected expression of mitochondrial Ca distribution regulators and PTEN-induced putative kinase 1 (PINK1). JC-1 was used to detect the mitochondrial membrane potential (Δψm) of cardiomyocytes.

Results: We found that expression of PINK1 decreased in mouse hearts during sepsis, which caused cardiomyocyte mitochondrial Ca efflux disorder, mitochondrial calcium overload, and cardiomyocyte injury. In contrast, we found that exosomes isolated from huMSCs (huMSC-exo) carried Pink1 mRNA, which could be transferred to recipient cardiomyocytes to increase PINK1 expression. The reduction in cardiomyocyte mitochondrial calcium efflux was reversed, and cardiomyocytes recovered from injury. We confirmed the effect of the PINK1-PKA-NCLX axis on mitochondrial calcium homeostasis in cardiomyocytes during sepsis.

Conclusion: The PINK1-PKA-NCLX axis plays an important role in mitochondrial calcium efflux in cardiomyocytes. Therefore, PINK1 may be a therapeutic target to protect cardiomyocyte mitochondria, and the application of huMSC-exo is a promising strategy against sepsis-induced heart dysfunction.
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http://dx.doi.org/10.1186/s13287-021-02325-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101124PMC
May 2021

MiR-205-5p suppresses angiogenesis in gastric cancer by downregulating the expression of VEGFA and FGF1.

Exp Cell Res 2021 Jul 4;404(2):112579. Epub 2021 May 4.

Department of General Surgery, Peking University First Hospital, Beijing, 100034, China. Electronic address:

Anti-angiogenic therapy represents one of the most promising treatment modalities for human cancers. However, the response to antiangiogenic therapy in gastric cancer (GC) remains dismal. To help identify new strategies for antiangiogenic therapy in GC, we evaluated miR-205-5p expression in GC tissues from TCGA database and our hospital, and its functions in angiogenesis were explored in vitro and in vivo. We investigated miR-205-5p expression and microvessel densities (MVDs) in GC tissues and liver metastases from patients. The function and mechanisms of miR-205-5p were examined in human cell lines and in xenograft mouse models. Associations between miR-205-5p expression and clinical characteristics were analyzed using either Pearson's χ test or Fisher's exact test. Differences in overall survival (OS) distributions were evaluated using the log-rank test. Differences in measurement data were compared using Student's t-test and one-way ANOVA. We found that miR-205-5p expression was downregulated in GC tissues and was negatively correlated with CD31 expression in both TCGA and our clinical samples. GC cell lines expressed low levels of miR-205-5p, and miR-205-5p upregulation significantly impaired the proliferation and angiogenesis of GC cells. Moreover, vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 1 (FGF1) expression and activation of extracellular-related kinase (ERK) signaling were suppressed by miR-205-5p. MiR-205-5p inhibition promoted malignant phenotypes by enhancing VEGFA and FGF1 expression, as well as the activation of ERK signaling. Angiogenesis and ERK signaling were decreased in response to VEGFA and FGF1 downregulation induced by miR-205-5p overexpression. The dual-luciferase reporter assay showed that VEGFA and FGF1 were direct targets of miR-205-5p. Xenograft mouse models revealed that miR-205-5p suppressed tumor growth by inhibiting neovascularization. Altogether, these results demonstrate that miR-205-5p suppresses angiogenesis in GC by attenuating the expression of VEGFA and FGF1, indicating that upregulation of miR-205-5p may represent as an antiangiogenic therapy for GC.
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http://dx.doi.org/10.1016/j.yexcr.2021.112579DOI Listing
July 2021

A nonsynonymous polymorphism (rs117179004, T392M) of hyaluronidase 1 (HYAL1) is associated with increased risk of idiopathic pulmonary fibrosis in Southern Han Chinese.

J Clin Lab Anal 2021 Jun 4;35(6):e23782. Epub 2021 May 4.

Department of Internal Medicine and Genetic Diagnosis Center, Tongji Hospital, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan, China.

Background: Idiopathic pulmonary fibrosis (IPF) is a genetic heterogeneous disease with high mortality and poor prognosis. Hyaluronidase 1 (HYAL1) was found to be upregulated in fibroblasts from IPF patients, and overexpression of HYAL1 could prevent human fetal lung fibroblast proliferation. However, the genetic correlation between the HYAL1 and IPF or connective tissue diseases related interstitial lung disease (CTD-ILD) has not been determined.

Methods: A two-stage study was conducted in Southern Han Chinese population. We sequenced the coding regions and flanking regulatory regions of HYAL1 in stage one (253 IPF cases and 125 controls). A statistically significant variant was further genotyped in stage two (162 IPF cases, 182 CTD-ILD cases, and 225 controls).

Results: We identified a nonsynonymous polymorphism (rs117179004, T392M) significantly associated with increased IPF risk (dominant model: OR = 2.239, 95% CI = 1.212-4.137, p = 0.010 in stage one; OR = 2.383, 95% CI = 1.376-4.128, p = 0.002 in stage two). However, we did not observe this association in CTD-ILD (OR = 1.401, 95% CI = 0.790-2.485, p = 0.248).

Conclusion: Our findings suggest that the nonsynonymous polymorphism (rs117179004, T392M) may confer susceptibility to IPF in Southern Han Chinese, but is not associated with susceptibility to CTD-ILD.
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http://dx.doi.org/10.1002/jcla.23782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183947PMC
June 2021