Publications by authors named "Kun Xiao"

137 Publications

Advances in the Regulation of Macrophage Polarization by Mesenchymal Stem Cells and Implications for ALI/ARDS Treatment.

Front Immunol 2022 8;13:928134. Epub 2022 Jul 8.

Center of Pulmonary & Critical Care Medicine, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a common condition with high mortality. ALI/ARDS is caused by multiple etiologies, and the main clinical manifestations are progressive dyspnea and intractable hypoxemia. Currently, supportive therapy is the main ALI/ARDS treatment, and there remains a lack of targeted and effective therapeutic strategies. Macrophages are important components of innate immunity. M1 macrophages are pro-inflammatory, while M2 macrophages are anti-inflammatory and promote tissue repair. Mesenchymal stem cells (MSCs) are stem cells with broad application prospects in tissue regeneration due to their multi-directional differentiation potential along with their anti-inflammatory and paracrine properties. MSCs can regulate the balance of M1/M2 macrophage polarization to improve the prognosis of ALI/ARDS. In this paper, we review the mechanisms by which MSCs regulate macrophage polarization and the signaling pathways associated with polarization. This review is expected to provide new targets for the treatment of ALI/ARDS.
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http://dx.doi.org/10.3389/fimmu.2022.928134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307903PMC
July 2022

Mechanism of TLR4 mediated immune effect in transfusion-induced acute lung injury based on Slit2/Robo4 signaling pathway.

Transfus Apher Sci 2022 Jul 8:103500. Epub 2022 Jul 8.

Department of Transfusion Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China. Electronic address:

Background: Transfusion-related acute lung injury (TRALI) is the infusion of blood or blood system.

Objective: To explore the mechanism of TLR4-mediated T cell immune effect in TRALI.

Methods: In this animal study, a mouse model of LPS-induced TRALI was established. Sixty adult C57/BL6 mice (wild-type, WT) were randomly divided into 5 groups: 1) normal WT type, 2) LPS control group of WT type lipopolysaccharide, 3) WT type TRALI group (LPS + MHC-I mAb), 4) (TLR4 antibody) lipopolysaccharide LPS control group, 5) (TLR4 antibody) TRALI group (LPS + MHC-I mAb). Mice were injected with LPS (0.1 mg/kg) and MHC-I mAb (2 mg/kg) into the tail vein. H&E staining was performed to detect pathological features. The myeloperoxidase (MPO) activity and the level of inflammatory cytokines in lung tissue homogenate supernatant were measured. Blood, spleen single-cell suspension, and bronchoalveolar lavage fluid were collected to detect the ratio of Treg and Th17 cells by flow cytometry. RT-PCR and WB were used to detect mRNA or protein expression.

Results: TLR4 mAb treatment alleviated the pathogenesis of LPS-induced TRALI in vivo, the MPO activity, and the level of proinflammatory factors in lung tissues. TLR4 exerted its function by changing of Treg/Th17 ratio via the SLIT2/ROBO4 signaling pathway and downregulating CDH5 and SETSIP.

Conclusion: TLR4 mediates immune response in the LPS-induced TRALI model through the SLIT2/ROBO4 signaling pathway.
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http://dx.doi.org/10.1016/j.transci.2022.103500DOI Listing
July 2022

Administration of krill oil extends lifespan of fish Nothobranchius guentheri via enhancement of antioxidant system and suppression of NF-κB pathway.

Fish Physiol Biochem 2022 Jul 14. Epub 2022 Jul 14.

Institute of Evolution & Marine Biodiversity and Department of Marine Biology, Ocean University of China, 5 Yushan Road, Qingdao, 266003, China.

Krill oil (KO) extracted from Antarctic krill (Euphausia superba) mainly comprises phospholipids and triglycerides. KO has been shown to prolong the median lifespan of the nematode Caenorhabditis elegans, but to shorten the lifespan of long-lived F1 mice; therefore, it remains controversial over the life-extending property of KO. In this study, we clearly demonstrated that dietary intake of KO extended both the mean and maximum lifespans of aged male Nothobranchius guentheri (p < 0.05), reduced the accumulation of lipofuscin (LF) (p < 0.05) in the gills and senescence-associated β-galactosidase (SA-β-Gal) (p < 0.05) in the caudal fins, and lowered the levels of protein oxidation (p < 0.05), lipid peroxidation (p < 0.01), and reactive oxygen species (ROS) (p < 0.01) in the muscles and livers, indicating that KO possesses rejuvenation and anti-aging activity. We also showed that KO enhanced the activities of antioxidant enzymes catalase (CAT) (p < 0.05), superoxide dismutase (SOD) (p < 0.05), and glutathione peroxidase (GPX) (p < 0.05) in aged male N. guentheri. In addition, KO administration effectively reversed histological lesions including inflammatory cell infiltration and structural collapse in the muscles and livers of aged N. guentheri and suppressed the nuclear factor kappa-B (NF-κB) signaling pathway (p < 0.05), a master regulator of inflammation. Altogether, our study indicates that KO has anti-aging and rejuvenation property. It also suggests that KO exerts its anti-aging and rejuvenation effects via enhancement of the antioxidant system and suppression of the NF-κB signaling pathway.
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http://dx.doi.org/10.1007/s10695-022-01102-3DOI Listing
July 2022

TMEM106A transcriptionally regulated by promoter methylation is involved in invasion and metastasis of hepatocellular carcinoma.

Acta Biochim Biophys Sin (Shanghai) 2022 May 25. Epub 2022 May 25.

Liver Cancer Institute, Zhongshan Hospital, Fudan University & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200032, China.

Expression of transmembrane protein 106A (TMEM106A) has been reported to be dysregulated in several types of cancers. However, the role of TMEM106A in hepatocellular carcinoma (HCC) is still unknown. In the present study, we demonstrate that TMEM106A is markedly downregulated in HCC compared with normal liver tissue. In particular, tumor-specific DNA methylation of TMEM106A is frequently observed in tumor tissues from HCC patients. Immunohistochemistry and pyrosequencing reveal a significant relationship between TMEM106A methylation and downregulation of protein expression. Receiver operating characteristic (ROC) curve analysis reveals that methylation of TMEM106A in tumor samples is different from that in non-malignant adjacent tissues of HCC patients. Moreover, HCC patients with TMEM106A hypermethylation have a poor clinical prognosis. 5-Aza-2'-deoxycytidin treatment of hypermethylated TMEM106A in highly metastatic HCC cells increases the expression of TMEM106A. Functional assays reveal that overexpression of TMEM106A significantly suppresses the malignant behavior of HCC cells in vitro and decreases tumorigenicity and lung metastasis in vivo. Mechanistically, TMEM106A inhibits epithelial mesenchymal transition (EMT) of HCC cells through inactivation of the Erk1/2/Slug signaling pathway. In conclusion, our findings demonstrate that TMEM106A is an inhibitor of HCC EMT and metastasis, and TMEM106A is often transcriptionally downregulated by promoter methylation, which results in reduced levels of TMEM106A protein and predicts poor survival outcomes for HCC patients.
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http://dx.doi.org/10.3724/abbs.2022069DOI Listing
May 2022

The First National Remote Emergency System for Malignant Hyperthermia (MH-NRES) in China: Protocol for the Design, Development, and Evaluation of a WeChat Applet.

JMIR Res Protoc 2022 Jun 10;11(6):e37084. Epub 2022 Jun 10.

Department of Anesthesiology, Sichuan University West China Hospital, Chengdu, China.

Background: Malignant hyperthermia (MH) is a rare life-threatening anesthetic emergency. With respect to the high fatality rate, difficulty in early recognition, and the lack of disease-specific drug (ie, dantrolene) in China, more effort is needed to strengthen early diagnosis and effective treatment of MH emergencies. Nowadays, mobile health (mHealth) apps are changing the way of medical practice; they can serve as an accessible tool to help anesthesiologists deal with MH crises. However, no related mHealth-based emergency system is available currently.

Objective: The aim of this study is to outline the protocol for the development of a WeChat applet used to design a National Remote Emergency System for Malignant Hyperthermia (MH-NRES) in China, as well as the protocol for the evaluation of the user experience and perception of the system.

Methods: The system adopts the client-server architecture, with a custom user interface operating as clients and the back-end system operating as the server. The client-side software was developed using uni-app technology with Vue.js-based framework, which consists of 6 modules: Quick Diagnosis, Dantrolene Mobilization, Instruction on Dantrolene Use, MH Treatment, Recovery Period Treatment, and DNA Test and Biopsy. The back-end system was developed based on the Spring framework. The system will be evaluated by administrating a modified user version of the Mobile App Rating Scale. Pilot testing will be conducted in Sichuan Province, China, and a subsequent evaluation on a national scale is planned.

Results: The theoretical framework design of this system was completed in August 2021. The development of the system was completed in February 2022, and the refinement is currently ongoing. Pilot testing after the implementation of the system in Sichuan Province is planned to take 2 months, and the subsequent evaluation on a national scale is planned to take 2 months.

Conclusions: We have described a novel approach using the WeChat applet to develop the MH-NRES. Findings from the usability testing process in the current study may lead to refinements and is expected to suggest that this system is both feasible and welcomed by anesthesiologists. Depending on the availability of research funding, this system will be extended nationally across China.

International Registered Report Identifier (irrid): PRR1-10.2196/37084.
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http://dx.doi.org/10.2196/37084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233253PMC
June 2022

Association Between Cerebral Autoregulation and Long-Term Outcome in Patients With Acute Ischemic Stroke.

Neurologist 2022 May 23. Epub 2022 May 23.

Department of Neurology, the First Affiliated Hospital of Shenzhen University Shenzhen Second People's Hospital.

Background: Dynamic cerebral autoregulation (CA) is known to be impaired in patients with acute ischemic stroke (AIS), but whether or not dynamic CA can predict long-term outcomes is unclear.

Materials And Methods: This prospective study included 103 patients with AIS between September 2017 and April 2019. We measured the middle cerebral artery blood flow velocity and blood pressure within 7 days of AIS onset using a transcranial Doppler and Finometer, respectively. We conducted transfer function analysis to calculate dynamic CA indices (phase and gain), with lower phase and higher gain parameters reflecting less efficient CA. We followed up all patients after 3 and 12 months. Patients with 12-month modified Rankin Scale scores of <2 and ≥2 were defined as having favorable and unfavorable outcomes, respectively. We then analyzed the predictors of unfavorable outcomes after 3 and 12 months using logistic regression.

Results: The ipsilesional phase parameter was significantly lower in patients with unfavorable outcomes than in those with favorable outcomes. Multiple logistic regression analysis revealed that the ipsilesional phase parameter and the National Institutes of Health Stroke Scale score were nonmodifiable predictors of short-term and long-term outcomes. Moreover, in receiver operating characteristic analysis, the area under the curve of the ipsilesional phase parameter was 0.646 (95% confidence interval: 0.513-0.779, P=0.044). Notably, the optimal cut-off value was 20.33 degrees (sensitivity: 63%, specificity: 70%).

Conclusion: Dynamic CA is an independent predictor of outcomes at 3 and 12 months in patients with AIS.
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http://dx.doi.org/10.1097/NRL.0000000000000422DOI Listing
May 2022

Case Report: Abdominal Cocoon With Jejuno-Ileo-Colonic Fistula.

Front Surg 2022 28;9:856583. Epub 2022 Apr 28.

Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Introduction: Abdominal cocoon is a unique peritoneal disease that is frequently misdiagnosed. The occurrence of the abdominal cocoon with a jejuno-ileo-colonic fistula has not been previously reported.

Case Presentation: We admitted a 41-year-old female patient with an abdominal cocoon and a jejuno-ileo-colonic fistula. She was admitted to our hospital for the following reasons: "the menstrual cycle is prolonged for half a year, and fatigue, palpitations, and shortness of breath for 2 months". On the morning of the 4th day of admission, the patient experienced sudden, severe, and intolerable abdominal pain after defecating. An emergency abdominal CT examination revealed intestinal obstruction. Surgery was performed, and the small intestine and colon were observed to be conglutinated and twisted into a mass surrounded by a fibrous membrane, and an enteroenteric fistula was observed between the jejunum, ileum, and sigmoid colon. We successfully relieved the intestinal obstruction and performed adhesiolysis. The patient was discharged from our hospital on the 6th postoperative day, then she recovered and was discharged from Feicheng People's Hospital after another 11 days of conservative treatment, and she recovered well-during the 2-month follow-up period.

Conclusion: Abdominal cocoon coexisting with a jejuno-ileo-colonic fistula is very rare. During the process of abdominal cocoon treatment, the patient's medical history should be understood in detail before the operation, and the abdominal organs should be carefully evaluated during the operation to avoid missed diagnoses.
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http://dx.doi.org/10.3389/fsurg.2022.856583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9095931PMC
April 2022

Early prediction of moderate-to-severe condition of inhalation-induced acute respiratory distress syndrome via interpretable machine learning.

BMC Pulm Med 2022 May 12;22(1):193. Epub 2022 May 12.

College of Pulmonary and Critical Care Medicine, Chinese People's Liberation Army General Hospital, Beijing, 100853, China.

Background: Several studies have investigated the correlation between physiological parameters and the risk of acute respiratory distress syndrome (ARDS), in addition, etiology-associated heterogeneity in ARDS has become an emerging topic quite recently; however, the intersection between the two, which is early prediction of target conditions in etiology-specific ARDS, has not been well-studied. We aimed to develop and validate a machine-learning model for the early prediction of moderate-to-severe condition of inhalation-induced ARDS.

Methods: Clinical expertise was applied with data-driven analysis. Using data from electronic intensive care units (retrospective derivation cohort) and the three most accessible vital signs (i.e. heart rate, temperature, and respiratory rate) together with feature engineering, we applied a random forest approach during the time window of 90 h that ended 6 h prior to the onset of moderate-to-severe respiratory failure (the ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ≤ 200 mmHg).

Results: The trained random forest classifier was validated using two independent validation cohorts, with an area under the curve of 0.9127 (95% confidence interval 0.8713-0.9542) and 0.9026 (95% confidence interval 0.8075-1), respectively. A Stable and Interpretable RUle Set (SIRUS) was used to extract rules from the RF to provide guidelines for clinicians. We identified several predictive factors, including resp_96h_6h_min < 9, resp_96h_6h_mean ≥ 16.1, HR_96h_6h_mean ≥ 102, and temp_96h_6h_max > 100, that could be used for predicting inhalation-induced ARDS (moderate-to-severe condition) 6 h prior to onset in critical care units. ('xxx_96h_6h_min/mean/max': the minimum/mean/maximum values of the xxx vital sign collected during a 90 h time window beginning 96 h prior to the onset of ARDS and ending 6 h prior to the onset from every recorded blood gas test).

Conclusions: This newly established random forest‑based interpretable model shows good predictive ability for moderate-to-severe inhalation-induced ARDS and may assist clinicians in decision-making, as well as facilitate the enrolment of patients in prevention programmes to improve their outcomes.
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http://dx.doi.org/10.1186/s12890-022-01963-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098141PMC
May 2022

Glucose-PEG2000-DSPE modified carbamazepine nano system alleviated cell apoptosis and oxidative stress in epilepsy.

Nucleosides Nucleotides Nucleic Acids 2022 15;41(7):671-683. Epub 2022 Apr 15.

Department of Neurology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.

Investigations on the effects of newly constructed glucose-PEG2000-DSPE modified carbamazepine nano system on oxidative stress damage and cell apoptosis in epilepsy. The nano system was constructed by egg yolk lecithin, cholesterol, GLUPEG2000-DSPE, and carbamazepine as per the molar ratio of 95:20:5:6.35. The particle size, zeta potential, and release rate of carbamazepine was determined using a microscope and a microplate reader. The cells toxicity was detected for determine the optimal concentration of carbamazepine nano system. Cell uptake, cell apoptosis ratio and ROS level was determined by flow cytometry analysis. The in vivo studies were performed using male Wistar rats. H&E staining was employed for histological evaluation. Immunofluorescence was utilized for measure the expression level of GLUT1. ELISA assay was obtained for detecting the levels of SOD, GSH-Px and MDA. The results shown the average particle size was 108.57 ± 3.42 nm, and the mean zeta potential was -52.75 ± 1.48 mV. The modified carbamazepine liposomes exhibited higher release rate. Cell uptake indicated that carbamazepine nano system could be successfully internalized into cells. Flow cytometry analysis revealed the carbamazepine nano system dramatically decreased cell apoptosis rate and downregulated ROS level. Moreover, carbamazepine nano system improved histological status, increased GLUT1 expression and decreased oxidative stress in vivo. In conclusion, glucose-PEG2000-DSPE modified carbamazepine nano system ameliorated cell apoptosis and oxidative stress damage in epilepsy.
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http://dx.doi.org/10.1080/15257770.2022.2061714DOI Listing
July 2022

Correlation Analysis of the Microbiome and Immune Function in the Lung-Gut Axis of Critically Ill Patients in the ICU.

Front Med (Lausanne) 2022 18;9:808302. Epub 2022 Mar 18.

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

Objective: Critical illnesses in the intensive care unit (ICU) have been a global burden. We aimed to determine the correlation between the lung and gut in critically ill patients to find novel evidence of the lung-gut axis, which may be a new treatment for patients with critical illness in the ICU.

Methods: We collected bronchoalveolar lavage specimens and fecal samples of 31 patients with critical illness within 24 h after admission. Metagenomics was used to detect lung and intestinal samples. Immune cells were detected by flow cytometry.

Results: There are 86 common species in both lung and gut. The abundance of is high in both the lung and gut of patients with critical illness in the respiratory intensive care unit (RICU). in the lung and gut is correlated with different immune cells. In addition, in the lung and gut might share the same source, supporting the concept of a gut-lung axis in humans.

Conclusions: The microbiome in the lung and gut showed a correlation to some extent, and in the lung and gut might share the same source. In addition, the microbiome showed a correlation with immunity, indicating a potential therapeutic target in patients with critical illness. The lung-gut axis might play an important role in patients with critical illness in the RICU.
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http://dx.doi.org/10.3389/fmed.2022.808302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971608PMC
March 2022

Impact of preceding noncurative endoscopic submucosal dissection on patients with early gastric cancer who undergo subsequent surgery: a meta-analysis.

Expert Rev Gastroenterol Hepatol 2022 Apr 4;16(4):373-382. Epub 2022 Apr 4.

Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China.

Background: The influence of preceding noncurative endoscopic submucosal dissection (ESD) on the efficacy of subsequent surgery is still controversial among early gastric cancer (EGC), especially for laparoscopic gastrectomy. The present meta-analysis was conducted to compare clinical outcomes between patients with EGC who underwent noncurative ESD before surgery (ESD group) and those who underwent direct surgery (non-ESD group).

Methods: Related databases were searched, and articles comparing differences between ESD and non-ESD groups were included for meta-analysis.

Results: Ten retrospective studies with 3465 participants were included in this meta-analysis. Compared with the non-ESD group, the ESD group was older and had more males, smaller tumors, more differentiated tumors and a higher proportion of pT1b, a shorter operation time, fewer dissected lymph nodes, a lower rate of positive lymph nodes and a lower rate of D2 dissection. There was no significant difference in intraoperative blood loss, postoperative complication rate, postoperative hospital stay or long-term prognosis, etc.

Conclusion: Preceding noncurative ESD has no negative impact on the short- and long-term results of additional gastrectomy (open surgery or laparoscopic surgery).
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http://dx.doi.org/10.1080/17474124.2022.2057298DOI Listing
April 2022

Corrigendum: VvMYB15 and VvWRKY40 Positively Co-regulated Anthocyanin Biosynthesis in Grape Berries in Response to Root Restriction.

Front Plant Sci 2022 22;13:850160. Epub 2022 Feb 22.

Department of Plant Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.

[This corrects the article DOI: 10.3389/fpls.2021.789002.].
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http://dx.doi.org/10.3389/fpls.2022.850160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906401PMC
February 2022

Characterization of Five Effectors Associated with PsoRPM3.

Int J Mol Sci 2022 Jan 28;23(3). Epub 2022 Jan 28.

Laboratory of Fruit Physiology and Molecular Biology, China Agricultural University, Beijing 100193, China.

Root-knot nematodes (RKNs) are devastating parasites that invade thousands of plants. In this study, five RKN effectors, which might interact with resistance protein PsoRPM3, were screened and identified. In situ hybridisation results showed that MiCal, MiGST_N_4, MiEFh and MiACPS are expressed in the subventral oesophageal glands (SvG), and MiTSPc hybridization signals are found in the dorsal esophageal gland (DG) of in the pre-J2. RT-qPCR data indicated that the expression of , , , and genes are highly expressed in of pra-J2 and J3/J4 stages. The expression of increased significantly in the female stage of . Moreover, all effectors found in this study localize in the cytoplasm and nucleus when transiently expressed in plant cells. In addition, MiGST_N_4, MiEFh, MiACPS and MiTSPc can elicit the ROS burst and strong hypersensitive response (HR), as well as significant ion leakage. Our data suggest that MiGST_N_4, MiEFh, MiACPS and MiTSPc effectors may be involved in triggering the immune response of the host plant.
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http://dx.doi.org/10.3390/ijms23031498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8836280PMC
January 2022

Potential roles of vitamin D binding protein in attenuating liver injury in sepsis.

Mil Med Res 2022 01 20;9(1). Epub 2022 Jan 20.

Center of Pulmonary and Critical Care Medicine, Chinese People's Liberation Army (PLA) General Hospital, No. 28, Fuxing Street, Haidian District, Beijing, 100853, China.

Background: In sepsis, vitamin D binding protein (VDBP) has been shown to be low-expressed. The current study examined the relationship between serum VDBP level and liver injury in sepsis patients, as well as in a mouse model for sepsis and in cultured liver epithelial cell line exposed to lipopolysaccharide (LPS).

Methods: The human study included 78 sepsis patients and 50 healthy volunteers. Sepsis patients were categorized into sepsis survivor group (n = 43) and sepsis non-survivor group (n = 35) based on 28-day mortality for data analysis. Adult male C57BL/6 mice were subjected to cecal ligation and puncture (CLP). Serum samples were collected on day 1, 3, 5 and 7 to determine the levels of VDBP, 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)D], interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Potential protective effects of VDBP overexpression against LPS-induced liver damage were examined in cultured THLE2 cells.

Results: Serum levels of VDBP, 25(OH)D, and 1,25(OH)D were significantly lower in sepsis patients vs. the healthy control (P < 0.001), as well as in the sepsis non-survivor group vs. the sepsis survivor group (P < 0.001, P = 0.0338, or P = 0.0013, respectively). Lower serum VDBP level was associated with higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (r = - 0.2565, P = 0.0234) and Sequential Organ Failure Assessment score (r = - 0.3522, P = 0.0016), but lower serum albumin (ALB, r = 0.4628, P < 0.001) and total protein (TP, r = 0.263, P = 0.02). In CLP mice, there was a 5-day period of serum VDBP reduction, followed by return towards the baseline on day 7. VDBP was also decreased in LPS-treated THLE2 cells (P < 0.001). VDBP overexpression reduced LPS-induced THLE2 damage. Reduced damage was associated with decreased oxidative stress and inactivation of the c-Jun N-terminal kinase signaling pathway.

Conclusion: VDBP may be protective against sepsis-induced liver injury.
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http://dx.doi.org/10.1186/s40779-022-00365-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772176PMC
January 2022

VvMYB15 and VvWRKY40 Positively Co-regulated Anthocyanin Biosynthesis in Grape Berries in Response to Root Restriction.

Front Plant Sci 2021 9;12:789002. Epub 2021 Dec 9.

Department of Plant Science, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.

In most grapevine planting regions, especially in south of China, plenty of rainfall and high water level underground are the characteristic of the area, a series of problem during fruit ripening easily caused poor color quality. Thereby affecting fruit quality, yield and economic benefits. The accumulation of anthocyanin is regulated by transcriptional regulatory factor and a series of cultivation measures, root restriction can make plants in the environment of stress and stress relief, root restriction induced the higher expression of and , and consistent with anthocyanin accumulation. Whether and how root restriction-inducible VvMYB15 and VvWRKY40 transcription factor regulate anthocyanin synthesis in grape berry is still unclear. In this study, we identified that the transient overexpression of and alone or both in strawberry fruits and grape berries can promote anthocyanin accumulation and increase the expression level of anthocyanin biosynthetic genes, indicating VvMYB15 and VvWRKY40 play a positive regulator of anthocyanin biosynthesis. Furthermore, we confirmed that both VvMYB15 and VvWRKY40 specifically bind to the promoter region of '' and , and the expression of '' and is further activated through the heterodimer formation between VvMYB15 and VvWRKY40. Finally, we confirmed that VvMYB15 promoted anthocyanin accumulation by interacting with VvWRKY40 in grape berries, our findings provide insights into a mechanism involving the synergistic regulation of root restriction-dependent coloration and biosynthesis a VvMYB15 and VvWRKY40 alone or both in grape berries.
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http://dx.doi.org/10.3389/fpls.2021.789002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695491PMC
December 2021

Identification of MBW Complex Components Implicated in the Biosynthesis of Flavonoids in Woodland Strawberry.

Front Plant Sci 2021 8;12:774943. Epub 2021 Nov 8.

School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, China.

Flavonoids belong to the family of polyphenolic secondary metabolites and contribute to fruit quality traits. It has been shown that MBW complexes (MYB-bHLH-WD40) regulate the flavonoids biosynthesis in different plants, but only a limited number of MBW complexes have been identified in strawberry species in general. In this study, we identified 112 R2R3-MYB proteins in woodland strawberry; 12 of them were found to have potential functions in regulating flavonoids biosynthesis by phylogenetic analysis. qRT-PCR assays showed that , , , , , and mostly expressed at green stage of fruit development, aligned with proanthocyanidins accumulation; and showed higher expression levels at turning and ripe stages, aligned with anthocyanins accumulation. These results suggest that different MYBs might be involved in flavonoids biosynthesis at specific stages. Furthermore, FvMYB proteins were demonstrated to interact with FvbHLH proteins and induce expression from the promoters of and genes, which encode key enzymes in flavonoids biosynthesis. The co-expression of FvMYB and FvbHLH proteins in strawberry fruits also promoted the accumulation of proanthocyanidins. These findings confirmed and provided insights into the biofunction of MBW components in the regulation of flavonoid biosynthesis in woodland strawberry.
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http://dx.doi.org/10.3389/fpls.2021.774943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606683PMC
November 2021

N6-methyladenosine reader YTH N6-methyladenosine RNA binding protein 3 or insulin like growth factor 2 mRNA binding protein 2 knockdown protects human bronchial epithelial cells from hypoxia/reoxygenation injury by inactivating p38 MAPK, AKT, ERK1/2, and NF-κB pathways.

Bioengineered 2022 05;13(5):11973-11986

College of Pulmonary & Critical Care Medicine, Chinese People's Liberation Army (Pla) General Hospital, Beijing, China.

Lung ischemia/reperfusion (I/R) injury (LIRI) is a common complication after lung transplantation, embolism, and trauma. N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of I/R injury. However, there are no or few reports of m6A-related regulators in LIRI till now. In this text, dysregulated genes in lung tissues of LIRI rats versus the sham group were identified by RNA sequencing (RNA-seq). RNA-seq outcomes revealed that only YTH N6-methyladenosine RNA binding protein 3 (YTHDF3) and insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) were differentially expressed in the LIRI versus sham group among 20 m6A-related regulators. Next, the functions and molecular mechanisms of YTHDF3 and IGF2BP2 in LIRI were investigated in a hypoxia/reoxygenation-induced BEAS-2B cell injury model . Results showed that YTHDF3 or IGF2BP2 knockdown attenuated hypoxia/reoxygenation-mediated inhibitory effects on cell survival and cell cycle progression and inhibited hypoxia/reoxygenation-induced cell apoptosis and pro-inflammatory cytokine secretion in BEAS-2B cells. Genes that could be directly regulated by YTHDF3 or IGF2BP2 were identified based on prior experimental data and bioinformatics analysis. Moreover, multiple potential downstream pathways of YTHDF3 and IGF2BP2 were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis of the above-mentioned genes. Among these potential pathways, we demonstrated that YTHDF3 or IGF2BP2 knockdown inhibited hypoxia/reoxygenation-activated p38, ERK1/2, AKT, and NF-κB pathways in BEAS-2B cells. In conclusion, YTHDF3 or IGF2BP2 knockdown weakened hypoxia/reoxygenation-induced human lung bronchial epithelial cell injury by inactivating p38, AKT, ERK1/2, and NF-κB pathways.
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http://dx.doi.org/10.1080/21655979.2021.1999550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9211071PMC
May 2022

[A polycyclic aromatic hydrocarbon degrading strain and its potential of degrading phenanthrene in various enhanced systems].

Sheng Wu Gong Cheng Xue Bao 2021 Oct;37(10):3696-3707

Jiangxi Province Key Laboratory of Mining and Metallurgy Environmental Pollution Control, School of Resource and Environmental Engineering, Jiangxi University of Science and Technology, Ganzhou 341000, Jiangxi, China.

Polycyclic aromatic hydrocarbons (PAHs) are a class of common environmental pollutants that pose threats to human health. In this study, a mesophilic bacterial strain CFP312 (grown at 15-37 °C, optimal at 30 °C) was isolated from PAHs-contaminated soil samples. It was identified as Moraxella sp. by morphological observation, physiological and biochemical test, and 16S rRNA gene phylogeny analysis. This is the first reported PAHs degrading strains in Moraxella. Degradation analysis showed that 84% and 90% of the loaded phenanthrene (400 mg/L) were degraded within 48 h and 60 h, and the degradation rates reached 1.21 and 1.29 mg/(L·h), respectively. During the degradation of phenanthrene, phenanthrene-3,4-dihydrodiol was detected as an intermediate. Based on this, it was proposed that double oxygenation at the positions 3 and 4 of phenanthrene was the first step of biodegradation. Adaptability of strain CFP312 to different enhanced phenanthrene-degradation systems was tested in aqueous-organic system, micellar aqueous system, and cloud point system. Strain CFP312 showed good adaptability to different systems. In addition, the bacterium can rapidly degrade the phenanthrene in contaminated soil in slurry-aqueous system, indicating great potential in environmental remediation.
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http://dx.doi.org/10.13345/j.cjb.210212DOI Listing
October 2021

Targeting RNA with Next- and Third-Generation Sequencing Improves Pathogen Identification in Clinical Samples.

Adv Sci (Weinh) 2021 12 23;8(23):e2102593. Epub 2021 Oct 23.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.

Fast and accurate identification of microbial pathogens is critical for the proper treatment of infections. Traditional culture-based diagnosis in clinics is increasingly supplemented by metagenomic next-generation-sequencing (mNGS). Here, RNA/cDNA-targeted sequencing (meta-transcriptomics using NGS (mtNGS)) is established to reduce the host nucleotide percentage in clinic samples and by combining with Oxford Nanopore Technology (ONT) platforms (meta-transcriptomics using third-generation sequencing, mtTGS) to improve the sequencing time. It shows that mtNGS improves the ratio of microbial reads, facilitates bacterial identification using multiple-strategies, and discovers fungi, viruses, and antibiotic resistance genes, and displaying agreement with clinical findings. Furthermore, longer reads in mtTGS lead to additional improvement in pathogen identification and also accelerate the clinical diagnosis. Additionally, primary tests utilizing direct-RNA sequencing and targeted sequencing of ONT show that ONT displays important potential but must be further developed. This study presents the potential of RNA-targeted pathogen identification in clinical samples, especially when combined with the newest developments in ONT.
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http://dx.doi.org/10.1002/advs.202102593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8655164PMC
December 2021

Interaction between PSMD10 and GRP78 accelerates endoplasmic reticulum stress-mediated hepatic apoptosis induced by homocysteine.

Gut Pathog 2021 Oct 19;13(1):63. Epub 2021 Oct 19.

NHC Key Laboratory of Metabolic Cardiovascular Diseases Research, Yinchuan, 750004, Ningxia, People's Republic of China.

Background: The liver plays an important role in production and metabolism of homocysteine (Hcy), which has been reported to be involved in liver injury. In our previous work, we confirm that Hcy can induce liver injury by activating endoplasmic reticulum (ER) stress. However, the underlying mechanisms remain largely unknown.

Results: In present study, we established the Hcy-induced liver injury model by feeding cbs mice with high methionine diet, and found that a considerable mass of disordered arrangement of hepatocytes and enlarged space between hepatocytes were frequently occurred in the liver of cbs mice, accompanied with elevated expression levels of apoptosis-related proteins. In addition, Hcy could activate ER stress both in cbs mice and hepatocytes. Mechanistically, Hcy promoted the expression levels of proteasome 26S subunit non-ATPase 10 (PSMD10) in hepatocytes; and the expression of ER stress indicators and apoptosis-associated proteins were significantly suppressed when PSMD10 was silenced in hepatocytes under Hcy treatment. Moreover, bioinformatics analysis and luciferase reporter assay demonstrated that PSMD10 was a target gene of miR-212-5p. Consistently, miR-212-5p overexpression could inhibit ER stress-mediated apoptosis of hepatocytes under Hcy treatment. With the help of co-immunoprecipitation assay, we identified that the interaction between PSMD10 and GRP78 accelerated ER stress-mediated hepatic apoptosis induced by Hcy.

Conclusions: Our findings indicate that miR-212-5p directly targets PSMD10 and subsequently activates ER stress to promote Hcy-induced apoptosis of hepatocytes. We propose that endogenous PSMD10 physically interacts with GRP78 to regulate ER stress. Our study may provide the therapeutic target for the liver injury induced by Hcy.
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http://dx.doi.org/10.1186/s13099-021-00455-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8527788PMC
October 2021

Diversity of Macrophages in Lung Homeostasis and Diseases.

Front Immunol 2021 24;12:753940. Epub 2021 Sep 24.

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

Lung macrophages play important roles in the maintenance of homeostasis, pathogen clearance and immune regulation. The different types of pulmonary macrophages and their roles in lung diseases have attracted attention in recent years. Alveolar macrophages (AMs), including tissue-resident alveolar macrophages (TR-AMs) and monocyte-derived alveolar macrophages (Mo-AMs), as well as interstitial macrophages (IMs) are the major macrophage populations in the lung and have unique characteristics in both steady-state conditions and disease states. The different characteristics of these three types of macrophages determine the different roles they play in the development of disease. Therefore, it is important to fully understand the similarities and differences among these three types of macrophages for the study of lung diseases. In this review, we will discuss the physiological characteristics and unique functions of these three types of macrophages in acute and chronic lung diseases. We will also discuss possible methods to target macrophages in lung diseases.
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http://dx.doi.org/10.3389/fimmu.2021.753940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500393PMC
October 2021

Overexpression of PsoRPM3, an NBS-LRR gene isolated from myrobalan plum, confers resistance to Meloidogyne incognita in tobacco.

Plant Mol Biol 2021 Oct 1;107(3):129-146. Epub 2021 Oct 1.

Laboratory of Fruit Physiology and Molecular Biology, China Agricultural University, Beijing, China.

Key Messages: We reported an NBS-LRR gene, PsoRPM3, is highly expressed following RKN infection, initiating an HR response that promotes plant resistance. Meloidogyne spp. are root-knot nematodes (RKNs) that cause substantial economic losses worldwide. Screening for resistant tree resources and identifying plant resistance genes is currently the most effective way to prevent RKN infestations. Here, we cloned a novel TIR-NB-LRR-type resistance gene, PsoRPM3, from Xinjiang wild myrobalan plum (Prunus sogdiana Vassilcz.) and demonstrated that its protein product localized to the nucleus. In response to Meloidogyne incognita infection, PsoRPM3 gene expression levels were significantly higher in resistant myrobalan plum plants compared to susceptible plants. We investigated this difference, discovering that the - 309 to - 19 bp region of the susceptible PsoRPM3 promoter was highly methylated. Indeed, heterologous expression of PsoRPM3 significantly enhanced the resistance of susceptible tobacco plants to M. incognita. Moreover, transient expression of PsoRPM3 induced a hypersensitive response in tobacco, whereas RNAi-mediated silencing of PsoRPM3 in transgenic tobacco reduced this hypersensitive response. Several hypersensitive response marker genes were considerably up-regulated in resistant myrobalan plum plants when compared with susceptible counterparts inoculated with M. incognita. PsoPR1a (a SA marker gene), PsoPR2 (a JA marker gene), and PsoACS6 (an ET signaling marker gene) were all more highly expressed in resistant than in susceptible plants. Together, these results support a model in which PsoRPM3 is highly expressed following RKN infection, initiating an HR response that promotes plant resistance through activated salicylic acid, jasmonic acid, and ethylene signaling pathways.
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http://dx.doi.org/10.1007/s11103-021-01185-1DOI Listing
October 2021

Early correction of coagulopathy reduces the 28day mortality in adult patients with largearea burns.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Aug;46(8):851-857

Department of Blood Transfusion, First Affiliated Hospital of Nanchang University, Nanchang 330006.

Objectives: Coagulation dysfunction caused by large-area burns is an independent risk factor for the 28-day mortality of adult patients. However, whether early (48 hours after admission) correction of coagulopathy can reduce the 28-day mortality of adult patients with large-area burns has not been clarified. The purpose of this study was to investigate the effect of early correction of coagulopathy on the 28-day mortality in the adult patients with large-area burns.

Methods: Medical records of burn patients with blood transfusion who were hospitalized in the Department of Burn, First Affiliated Hospital of Nanchang University from April 2014 to July 2019 were retrieved. Among them, 573 adult patients with large-area burns were selected as the research subjects. The patients were divided into an experimental group (patients had early rectification of coagulation dysfunction, =290) and a control group (patients without early rectification of coagulation dysfunction, =283). The basic clinical data and prognostic indicators of the 2 groups were compared. Logistic univariate regression analysis was used to screen the influential factors of 28-day mortality in adult patients with large-area burns, and further logistic multivariate regression analysis was carried out to obtain independent risk factors and protective factors. Kaplan-Meier method was used to draw the survival curve for the 2 groups of patients, and log-rank test was used.

Results: The differences of the burn area/the total body surface area (TBSA), III° burn area, 24-hour urine volume and rehydration volume, 48-hour fresh frozen plasma transfusion volume, and 48-hour activated partial thromboplastin time (APTT) between the 2 groups were statistically significant (all <0.05). The duration of mechanical ventilation in the experimental group was shorter than that in the control group, and the 28-day mortality in the experimental group was significantly lower than that in the control group (10% vs 24%, both <0.05). The results of logistic univariate regression analysis showed that burn area/TBSA, III° burn area, inhalation injury, length of hospital stay, mechanical ventilation time, 48-hour frozen plasma infusion, and 48-hour coagulation dysfunction correction were the influential factors of 28-day mortality of adult patients with large-area burns and coagulation dysfunction at admission (all <0.05). Logistic multivariate regression analysis showed that the burn area/TBSA (OR=1.058, 95% CI 0.921 to 1.214, =0.022) and III° burn area (OR=1.085, 95% CI 1.009 to 1.168, =0.027) were independent risk factors for 28-day mortality of adult patients with large-area burns, while 48-hour frozen plasma transfusion volume (OR=0.098, 95% CI 0.012 to 0.789, =0.029) and 48-hour coagulation dysfunction correction (OR=0.103, 95% CI 0.015 to 0.679, =0.018) were independent protective factors. Kaplan-Meier survival curve analysis showed that 28-day survival rates of the experimental group and the control group were 90% and 76%, respectively. The difference between them was statistically significant (χ=14.270, <0.001).

Conclusions: The burn area/TBSA and III° burn area are independent risk factors for 28-day mortality in adult patients with large-area burns. The 48-hour frozen plasma transfusion volume and 48-hour correction of coagulopathy are independent protective factors. Early correction of coagulation dysfunction is beneficial to reducing the 28-day mortality for the adult patients with large-area burns.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.190817DOI Listing
August 2021

Novel Role of miR-18a-5p and Galanin in Rat Lung Ischemia Reperfusion-Mediated Response.

Oxid Med Cell Longev 2021 14;2021:6621921. Epub 2021 Aug 14.

Center of Pulmonary & Critical Care Medicine, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Lung ischemia reperfusion (IR) is known to occur after lung transplantation or cardiac bypass. IR leads to tissue inflammation and damage and is also associated with increased morbidity and mortality. Various receptors are known to partake in activation of the innate immune system, but the downstream mechanism of tissue damage and inflammation is yet unknown. MicroRNAs (miRNAs) are in the forefront in regulating ischemia reperfusion injury and are involved in inflammatory response. Here, we have identified by high-throughput approach and evaluated a distinct set of miRNAs that may play a role in response to IR in rat lung tissue. The top three differentially expressed miRNAs were validated through quantitative PCRs in the IR rat lung model and an model of IR of hypoxia and reoxygenation exposed type II alveolar cells. Among the miRNAs, miR-18a-5p showed consistent downregulation in both the model systems on IR. Cellular and molecular analysis brought to light a crucial role of this miRNA in ischemia reperfusion. miR-18a-5p plays a role in IR-mediated apoptosis and ROS production and regulates the expression of neuropeptide Galanin. It also influences the nuclear localization of transcription factor: nuclear factor-erythroid 2-related factor (Nrf2) which in turn may regulate the expression of the miR-18a gene. Thus, we have not only established a rat model for lung IR and enumerated the important miRNAs involved in IR but have also extensively characterized the role of miR-18a-5p. This study will have important clinical and therapeutic implications for and during transplantation procedures.
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http://dx.doi.org/10.1155/2021/6621921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8420977PMC
January 2022

Safety and efficacy of indocyanine green fluorescence imaging-guided radical gastrectomy: a systematic review and meta-analysis.

Expert Rev Gastroenterol Hepatol 2021 Nov 7;15(11):1319-1328. Epub 2021 Sep 7.

Department of Gastroenterological Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Background: The clinical value of indocyanine green (ICG) in laparoscopic radical gastrectomy remains controversial. We performed this meta-analysis to investigate the safety and efficacy of ICG fluorescence imaging-guided radical gastrectomy.

Methods: All relevant studies published until 30 October 2020 were retrieved from several databases. Fixed- and random-effects models were used to analyze the results based on different heterogeneity levels. Data were expressed as odds ratios or weighted mean differences along with 95% confidence intervals. The Grading of Recommendations, Assessment, Development, and Evaluation system scale was used for quality of evidence evaluation.

Results: This meta-analysis included six cohort studies that investigated 622 patients. Compared with conventional radical gastrectomy, ICG fluorescence imaging-guided gastrectomy facilitates complete lymph node dissection, reduces intraoperative blood loss, and shortens the length of postoperative hospitalization. Moreover, we observed no significant intergroup differences in the operative time, first exhaust time, and postoperative complications.

Conclusion: ICG fluorescence imaging-guided radical gastrectomy scores over conventional gastrectomy and appears to be a promising approach in patients who require radical gastrectomy. However, further research is warranted to explore the potential long-term survival benefit of ICG fluorescence imaging in patients with gastric cancer.
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http://dx.doi.org/10.1080/17474124.2021.1970530DOI Listing
November 2021

Albumin-Globulin Ratio Is an Independent Determinant of 28-Day Mortality in Patients with Critical Illness.

Dis Markers 2021 25;2021:9965124. Epub 2021 Aug 25.

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

Background: Critical illness in the intensive care unit (ICU) has been a global health priority. Systemic nutritional status has turned out to be related to the prognosis of critically ill patients. The albumin-globulin ratio (AGR) has been reported to be a novel prognostic factor of many diseases. This study is aimed at investigating whether the AGR could predict the mortality risk in critically ill patients.

Methods: We enrolled 582 adult patients admitted to the respiratory intensive care unit (RICU). We collected the clinical and laboratory data. X-tile software was used to determine the optimal cut-off values for the AGR. Patients were divided into three groups according to the AGR (low AGR group with AGR < 0.8, medium AGR group with AGR ranging from 0.8 to 1.1, and high AGR group with AGR > 1.1). Kaplan-Meier analysis was used for survival analysis. A Cox proportional hazard model was applied to the univariate and multivariate analyses for the potential predictors associated with survival.

Results: Our present study showed that the AGR was related to the 28-day survival of critically ill patients in the RICU. The rate of pneumonia in the low AGR group was significantly higher than that in the other groups. Patients with a lower AGR present an increased risk of 28-day mortality compared to patients with a higher AGR. Cox regression analysis showed that the AGR might be an independent predictor of prognosis to 28-day survival in critically ill patients in the RICU. Medium and high AGR values remained independently associated with better 28-day survival than low AGR values (HR: 0.484 (0.263-0.892) ( = 0.02); HR: 0.332 (0.166-0.665) ( = 0.002)).

Conclusion: The AGR might be an independent predictor of prognosis in critically ill patients.
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http://dx.doi.org/10.1155/2021/9965124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413056PMC
January 2022

Transcription Factor Assists Xinjiang Wild Myrobalan Plum () Disease Resistance Protein to Resist .

Plants (Basel) 2021 Jul 29;10(8). Epub 2021 Jul 29.

Laboratory of Fruit Physiology and Molecular Biology, China Agricultural University, Beijing 100193, China.

The root-knot nematode () causes huge economic losses in the agricultural industry throughout the world. Control methods against these polyphagous plant endoparasites are sparse, the preferred one being the deployment of plant cultivars or rootstocks bearing resistance genes against species. Our previous study has cloned one resistance gene, , from Xinjiang wild myrobalan plum (). However, the function of remains elusive. In the present study, we have investigated the regulatory mechanism of in plant defense responses to . Our results indicate that fewer giant cells were detected in the roots of the transgenic tobacco than wild tobacco lines after incubation with . Transient transformations of full-length and TN structural domains of have induced significant hypersensitive responses (HR), suggesting that TIR domain might be the one which caused HR. Further, yeast two-hybrid results revealed that the full-length and LRR domain of could interact with the transcription factor . The addition of increased the ROS levels and induced HR. Thus, our data revealed that the LRR structural domain of may be associated with signal transduction. Moreover, we did not find any relative inductions of defense-related genes , and in , which has been incubated with . In summary, our work has shown the key functional domain of in the regulation of defense responses to in .
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http://dx.doi.org/10.3390/plants10081561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402125PMC
July 2021

Decipering the Molecular Mechanism of ACE2 Regulating A549 Cells.

Front Genet 2021 19;12:653725. Epub 2021 Jul 19.

Center of Pulmonary and Critical Care Medicine, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Angiotensin-converting enzyme 2 (ACE2) is an aminopeptidase that functions as a part of the renin-angiotensin system (RAS). The RAS pathway plays a crucial role in regulating the local blood flow within a tissue. As a consequence, the role of ACE2 in regulating vasculature properties has been widely appreciated. Additionally, ACE2 has also been reported to show anti-tumorigenic activity. However, the mechanistic basis of this function has remained largely unexplored. In the current study, using a lentivirus-based expression system in lung cancer cells (A549), we show that ACE2 overexpression reduces the viability and migratory potential of cancer cells, highlighting the robust anti-tumorigenic effects of ACE2 function. Moreover, a quantitative proteome-level comparison between ACE2 overexpressed (OE) and empty vector-controlled (NC) cells reveals a large number (227) of differentially expressed proteins (DEPs) that may have contributed to this phenomenon. Functional enrichment of these DEPs has uncovered that most of them perform binding activities and enzymatic reactions associated with metabolic pathways and various post-transcriptional gene expression regulatory mechanisms. Besides, cellular component analysis reveals that the DEPs function across a range of compartments within a cell with a relatively heterogeneous distribution. Our study, therefore, supports the previously established anti-tumorigenic effects of ACE2 overexpression in lung cancer cells. An analysis based on comprehensive, unbiased, and quantitative proteomics, we have provided a rigorous mechanistic explanation for its functions.
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http://dx.doi.org/10.3389/fgene.2021.653725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8329961PMC
July 2021

Advances in mesenchymal stem cell-mediated tissue repair of lung injury.

Authors:
Kun Xiao Li-Xin Xie

Chronic Dis Transl Med 2021 Jun 31;7(2):75-78. Epub 2021 Mar 31.

Department of Pulmonary & Critical Care Medicine, Chinese PLA General Hospital, Beijing 100853, China.

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http://dx.doi.org/10.1016/j.cdtm.2021.02.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8180469PMC
June 2021

Effect of the infusion ration between frozen plasma and plasma substitutes on the prognosis of adult patients with major burn in shock stage.

Zhong Nan Da Xue Xue Bao Yi Xue Ban 2021 Apr;46(4):393-399

Department of Blood Transfusion, First Affiliated Hospital of Nanchang University, Nanchang 330006.

Objectives: In recent years, it has been reported that the anti-shock effect of plasma substitutes in adult patients with major burn in shock stage is not good. However, due to the shortage of clinical frozen plasma supply, it is impossible to guarantee that frozen plasma is used as colloidal solution for anti-shock treatment. The purpose of this study is to explore the effect of the infusion ration between frozen plasma and plasma substitutes on the prognosis of adult patients with major burn in shock stage.

Methods: This study enrolled 586 adult patients with major burn by selecting the hospitalization burn patients, who had been hospitalized at the Jiangxi province burn center from September 2014 to April 2019. The patients with the infusion ratio of frozen plasma to plasma substitutes ≥2꞉1 at 48 hours after admission were included in the experimental group, otherwise they were included in the control group. The basic clinical data and clinical prognosis indicator in the 2 groups were compared. Logistic univariate regression analysis was used to screen the influential factors of 30-day mortality in adult patients with major burn, and logistic multivariate regression analysis was used to obtain independent risk and protective factors; Kaplan-Meier method was used to draw the survival curve of the 2 groups, and log-rank test was used to compare the 30-day survival rate of the 2 groups.

Results: There were significant differences in the infusion volume of frozen plasma and plasma substitutes between the 2 groups at 48 hours after admission (both <0.05). The duration of mechanical ventilation in the experimental group was shorter than that in the control group, the percentage of continuous renal replacement therapy (CRRT) in the experimental group was lower than that in the control group, and the in-hospital mortality and 30-day mortality in the experimental group were lower than those in the control group, the differences were statistically significant (all <0.05). The percentage of burn area and total body surface area (TBSA) was an independent risk factor for 30-day mortality of adult patients with major burn (OR=1.228, 95% CI 1.010 to 1.439, =0.039), while the infusion ration between of frozen plasma and plasma substitutes 48 hours after admission was an independent protective factor (OR=0.016, 95% CI 0.001 to 0.960, =0.023). The 30-day survival rate of the experimental group was significantly higher than that in the control group (<0.001).

Conclusions: Infusion ration between frozen plasma to plasma substitutes at 48 hours after admission is an independent protective factor for 30-day mortality of adult patients with major burn. In the early stage of adult patients with major burn, frozen plasma should be used as the anti-shock therapy as far as possible (frozen plasma꞉plasma substitute ≥2꞉1) to improve the prognosis and reduce the of 30-day mortality.
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http://dx.doi.org/10.11817/j.issn.1672-7347.2021.190565DOI Listing
April 2021
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