Publications by authors named "Lai Jiang"

102 Publications

Ultra-efficient antimicrobial photodynamic inactivation system based on blue light and octyl gallate for ablation of planktonic bacteria and biofilms of Pseudomonas fluorescens.

Food Chem 2021 Nov 11:131585. Epub 2021 Nov 11.

School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, UK.

Pseudomonas fluorescens is a Gram-negative spoilage bacterium and dense biofilm producer, causing food spoilage and persistent contamination. Here, we report an ultra-efficient photodynamic inactivation (PDI) system based on blue light (BL) and octyl gallate (OG) to eradicate bacteria and biofilms of P. fluorescens. OG-mediated PDI could lead to a > 5-Log reduction of viable cell counts within 15 min for P. fluorescens. The activity is exerted through rapid penetration of OG towards the cells with the generation of a high-level toxic reactive oxygen species triggered by BL irradiation. Moreover, OG plus BL irradiation can efficiently not only prevent the formation of biofilms but also scavenge the existing biofilms. Additionally, it was shown that the combination of OG/poly(lactic acid) electrospun nanofibers and BL have great potential as antimicrobial packagings for maintaining the freshness of the salamander storge. These prove that OG-mediated PDI can provide a superior platform for eradicating bacteria and biofilm.
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http://dx.doi.org/10.1016/j.foodchem.2021.131585DOI Listing
November 2021

Surface engineering of oncolytic adenovirus for a combination of immune checkpoint blockade and virotherapy.

Biomater Sci 2021 Nov 9;9(22):7392-7401. Epub 2021 Nov 9.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics and Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361102, China.

Advances in the development of modern cancer immunotherapy and immune checkpoint inhibitors have dramatically changed the landscape of cancer treatment. However, most cancer patients are refractory to immune checkpoint inhibitors because of low lymphocytic tumor infiltration and PD-L1 expression. Evidence suggests that viral oncolysis and immune checkpoint inhibitors have a synergistic effect that can improve the response to immune checkpoint inhibitors. In this study, we developed bioengineered cell membrane nanovesicles (PD1-BCMNs) with programmed cell death protein 1 (PD-1) to harbor oncolytic adenovirus (OA) and achieve a combination of immune checkpoint blockade and oncolytic virotherapy in one particle for cancer treatment. PD1-BCMNs could specifically deliver OA to tumor tissue; the infectivity and replication ability of the OA was preserved in the presence of neutralizing antibodies and Selective oncolytic effects with oncolytic adenovirus led to an up-regulated expression of PD-L1 in the tumor microenvironment, turning immunologically 'cold' tumors into immunologically 'hot' tumors, presenting more targets for further enhanced target delivery. Notably, [email protected] could effectively activate tumor-infiltrating T cells and elicit a strong anti-tumor immune response. Thus, [email protected] may provide a clinical basis for combining oncolytic virotherapy with checkpoint inhibitors, enhancing the oncolytic adenovirus targeted delivery and significantly enhancing T cell immune responses, resulting in a stronger antitumor immunity response.
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http://dx.doi.org/10.1039/d1bm00928aDOI Listing
November 2021

Multi-Task Learning-Based Immunofluorescence Classification of Kidney Disease.

Int J Environ Res Public Health 2021 10 15;18(20). Epub 2021 Oct 15.

National Clinical Research Center for Kidney Diseases, State Key Laboratory of Kidney Diseases, Institute of Nephrology of Chinese PLA, Department of Nephrology, General Hospital of Chinese PLA, Medical School of Chinese PLA, Beijing 100853, China.

Chronic kidney disease is one of the most important causes of mortality worldwide, but a shortage of nephrology pathologists has led to delays or errors in its diagnosis and treatment. Immunofluorescence (IF) images of patients with IgA nephropathy (IgAN), membranous nephropathy (MN), diabetic nephropathy (DN), and lupus nephritis (LN) were obtained from the General Hospital of Chinese PLA. The data were divided into training and test data. To simulate the inaccurate focus of the fluorescence microscope, the Gaussian method was employed to blur the IF images. We proposed a novel multi-task learning (MTL) method for image quality assessment, de-blurring, and disease classification tasks. A total of 1608 patients' IF images were included-1289 in the training set and 319 in the test set. For non-blurred IF images, the classification accuracy of the test set was 0.97, with an AUC of 1.000. For blurred IF images, the proposed MTL method had a higher accuracy (0.94 vs. 0.93, < 0.01) and higher AUC (0.993 vs. 0.986) than the common MTL method. The novel MTL method not only diagnosed four types of kidney diseases through blurred IF images but also showed good performance in two auxiliary tasks: image quality assessment and de-blurring.
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http://dx.doi.org/10.3390/ijerph182010798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8535636PMC
October 2021

Joint Learning of Multi-level Tasks for Diabetic Retinopathy Grading on Low-resolution Fundus Images.

IEEE J Biomed Health Inform 2021 Oct 14;PP. Epub 2021 Oct 14.

Diabetic retinopathy (DR) is a leading cause of permanent blindness among the working-age people. Automatic DR grading can help ophthalmologists make timely treatment for patients. However, the existing grading methods are usually trained with high resolution (HR) fundus images, such that the grading performance decreases a lot given low resolution (LR) images, which are common in clinic. In this paper, we mainly focus on DR grading with LR fundus images. According to our analysis on the DR task, we find that: 1) image super-resolution (ISR) can boost the performance of both DR grading and lesion segmentation; 2) the lesion segmentation regions of fundus images are highly consistent with pathological regions for DR grading. Based on our findings, we propose a convolutional neural network (CNN)-based method for joint learning of multi-level tasks for DR grading, called DeepMT-DR, which can simultaneously handle the low-level task of ISR, the mid-level task of lesion segmentation and the high-level task of disease severity classification on LR fundus images. Moreover, a novel task-aware loss is developed to encourage ISR to focus on the pathological regions for its subsequent tasks: lesion segmentation and DR grading. Extensive experimental results show that our DeepMT-DR method significantly outperforms other state-of-the-art methods for DR grading over three datasets. In addition, our method achieves comparable performance in two auxiliary tasks of ISR and lesion segmentation.
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http://dx.doi.org/10.1109/JBHI.2021.3119519DOI Listing
October 2021

Salidroside protects against ventilation-induced lung injury by inhibiting the expression of matrix metalloproteinase-9.

Pharm Biol 2021 Dec;59(1):760-768

Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Context: Salidroside, a compound extracted from L. (Crassulaceae), possesses many beneficial pathological effects.

Objective: To explore the effect of salidroside on ventilator-induced lung endothelial dysfunction and .

Materials And Methods: , male ICR mice were divided into sham, ventilation, salidroside, and ventilation plus salidroside groups. The mice were ventilated for 4 h, salidroside (50 mg/kg) was administrated intraperitoneally before ventilation, dexamethasone (Dex) (5 mg/kg) was used as a positive control. , mouse lung vascular endothelial cells (MLVECs) were treated with salidroside, MMP-9 siRNA, and BAY11-7082 (10 μM), and then exposed to cyclic stretch for 4 h. Afterward, lung tissues and MLVECs were collected for further analysis.

Results: Salidroside pre-treatment significantly reversed the expression of vascular endothelial cadherin (VE-cadherin) and zonula occluden-1 (ZO-1) proteins in cyclic stretch-treated MLVECs (0.46 ± 0.09 0.80 ± 0.14, 0.49 ± 0.05 0.88 ± 0.08) and ventilated lung tissues (0.56 ± 0.06 0.83 ± 0.46, 0.49 ± 0.08 0.80 ± 0.12). The results further indicated that salidroside inhibited the expression of matrix metalloproteinase-9 (MMP-9), whereas knockdown of its expression restored the expression levels of VE-cadherin (0.37 ± 0.08 0.85 ± 0.74) and ZO-1 (0.48 ± 0.08 0.81 ± 0.11) in stretched MLVECs. Meanwhile, salidroside inhibited the NF-κB signalling pathway and alleviated lung injury.

Conclusions: Salidroside protected against stretch-induced endothelial barrier function, improving lung injury after ventilation. Thus, salidroside may be a promising therapeutic agent for patients with MV-induced lung injury.
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http://dx.doi.org/10.1080/13880209.2021.1967409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439245PMC
December 2021

Comparison of the curative effect and prognosis of stereotactic drainage and conservative treatment for moderate and small basal ganglia haemorrhage.

BMC Neurol 2021 Jul 6;21(1):268. Epub 2021 Jul 6.

Department of Ultrasound Diagnostics, The People's Hospital of China Three Gorges University, Yichang, 443000, China.

Background: Minimally invasive surgery has achieved good results in the treatment of cerebral haemorrhage.However, no large-scale clinical study has demonstrated that surgical treatment of cerebral haemorrhages less than 30 ml can improve the curative effect. Our study explored the efficacy and complication of stereotactic drainage based on the amount of cerebral hemorrhage (15-30 ml) in hypertensive basal ganglia.

Method: Sixty patients with hypertensive basal ganglia haemorrhages were divided into a control group and an experimental group with 30 patients in each group. Patients in the control group were treated conservatively. In contrast, those in the experimental group received stereotactic drainage, and urokinase was injected into the haematoma cavity after the operation. The haematoma volume at admission and 1, 3, 7 and 30 days after treatment and National Institute of Health stroke scale(NIHSS) score data were recorded. Complications after treatment in the two groups of data were compared and analysed.

Result: No significant differences in age, sex, time of treatment after onset, admission blood pressure, admission haematoma volume or admission NIHSS score were noted between these two groups (P > 0.05). After treatment, significant differences in haematoma volume were noted between the two groups on the 1st, 3rd, 7th and 30th days after treatment (P < 0.05). The amount of hematoma of patients in the experimental group was significantly reduced compared with that in the control group, and the NIHSS scores were significantly different on the 3rd, 7th and 30th days after treatment. The neurological deficit scores of patients in the experimental group were significantly reduced compared with those in the control group, and the incidence of pulmonary infection and venous thrombosis in the lower limbs of patients in the experimental group were significantly reduced (P < 0.05). ROC curve analysis showed that stereotactic drainage affected the early neurological function of patients with small and medium basal ganglia haemorrhages.

Conclusion: For patients with small and medium basal ganglia haemorrhages, stereotactic drainage can be used due to the faster drainage speed of haematomas after operation, which is beneficial to the recovery of neurological function and reduce complications.
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http://dx.doi.org/10.1186/s12883-021-02293-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258994PMC
July 2021

An integrated risk and epidemiological model to estimate risk-stratified COVID-19 outcomes for Los Angeles County: March 1, 2020-March 1, 2021.

PLoS One 2021 24;16(6):e0253549. Epub 2021 Jun 24.

Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States of America.

The objective of this study was to use available data on the prevalence of COVID-19 risk factors in subpopulations and epidemic dynamics at the population level to estimate probabilities of severe illness and the case and infection fatality rates (CFR and IFR) stratified across subgroups representing all combinations of the risk factors age, comorbidities, obesity, and smoking status. We focus on the first year of the epidemic in Los Angeles County (LAC) (March 1, 2020-March 1, 2021), spanning three epidemic waves. A relative risk modeling approach was developed to estimate conditional effects from available marginal data. A dynamic stochastic epidemic model was developed to produce time-varying population estimates of epidemic parameters including the transmission and infection observation rate. The epidemic and risk models were integrated to produce estimates of subpopulation-stratified probabilities of disease progression and CFR and IFR for LAC. The probabilities of disease progression and CFR and IFR were found to vary as extensively between age groups as within age categories combined with the presence of absence of other risk factors, suggesting that it is inappropriate to summarize epidemiological parameters for age categories alone, let alone the entire population. The fine-grained subpopulation-stratified estimates of COVID-19 outcomes produced in this study are useful in understanding disparities in the effect of the epidemic on different groups in LAC, and can inform analyses of targeted subpopulation-level policy interventions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253549PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224896PMC
July 2021

On the mechanism behind enhanced antibacterial activity of alkyl gallate esters against foodborne pathogens and its application in Chinese icefish preservation.

Food Microbiol 2021 Oct 20;99:103817. Epub 2021 Apr 20.

School of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, Zhejiang, 310035, China.

The objective of this study was to investigate antibacterial activities and action mode of alkyl gallates against three food-related bacteria. Results show that the length of the alkyl chain plays a critical role in eliciting their antibacterial activities and octyl gallate (GAC8) exhibited an outstanding bactericidal effect against these strains. A possible bactericidal mechanism of GAC8 against E. coli was fully elucidated by analyzing associated changes in cellular functions of E. coli, including assessments of membrane modification and intracellular oxidation state. Our data strongly suggested that GAC8 functions outside and inside the bacterial membrane and causes increased intracellular reactive oxygen species (hydroxyl radicals) and subsequent oxidative damage. We demonstrated that the hydroxyl radical formation induced by GAC8 is the end product of an oxidative damage cellular death pathway involving a transient depletion of NADH, the tricarboxylic acid cycle, intrinsic redox cycling activities, and stimulation of the Fenton reaction. Also, chitosan-based edible films containing GAC8 have unique superiorities for icefish preservation at 4 °C. This research highlights the effectiveness of GAC8 as an attractive antibacterial, which possesses both antioxidant and antibacterial activities and can be used as a multifunctional food additive combined with the benefit of active packaging for food preservations.
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http://dx.doi.org/10.1016/j.fm.2021.103817DOI Listing
October 2021

Intelligent Nanoparticle-Based Dressings for Bacterial Wound Infections.

ACS Appl Bio Mater 2021 May 9;4(5):3849-3862. Epub 2020 Dec 9.

School of Materials Science & Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore.

Conventional wound dressing materials containing free antibiotics for bacterial wound infections are presented with several limitations, that is, lack of controlled and triggered release capabilities, and may often not be adequate to address the complex bacteria microenvironment of such infections. Additionally, the improper usage of antibiotics may also result in the emergence of drug resistant strains. While delivery systems (i.e., nanoparticles) that encapsulate antibiotics may potentially overcome some of these limitations, their therapeutic outcomes are still less than desirable. For example, premature drug release or unintended drug activation may occur, which would greatly reduce treatment efficacy. To address this, responsive nanoparticle-based antimicrobial therapies could be a promising strategy. Such nanoparticles can be functionalized to react to a single stimulus or multi stimulus within the bacteria microenvironment and subsequently elicit a therapeutic response. Such "intelligent" nanoparticles can be designed to respond to the microenvironment, that is, an acidic pH, the presence of specific enzymes, bacterial toxins, etc. or to an external stimulus, for example, light, thermal, etc. These responsive nanoparticles can be further incorporated into wound dressings to better promote wound healing. This review summarizes and highlights the recent progress on such intelligent nanoparticle-based dressings as potential wound dressings for bacteria-infected wounds, along with the current challenges and prospects for these technologies to be successfully translated into the clinic.
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http://dx.doi.org/10.1021/acsabm.0c01168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155196PMC
May 2021

Joint Learning of 3D Lesion Segmentation and Classification for Explainable COVID-19 Diagnosis.

IEEE Trans Med Imaging 2021 09 31;40(9):2463-2476. Epub 2021 Aug 31.

Given the outbreak of COVID-19 pandemic and the shortage of medical resource, extensive deep learning models have been proposed for automatic COVID-19 diagnosis, based on 3D computed tomography (CT) scans. However, the existing models independently process the 3D lesion segmentation and disease classification, ignoring the inherent correlation between these two tasks. In this paper, we propose a joint deep learning model of 3D lesion segmentation and classification for diagnosing COVID-19, called DeepSC-COVID, as the first attempt in this direction. Specifically, we establish a large-scale CT database containing 1,805 3D CT scans with fine-grained lesion annotations, and reveal 4 findings about lesion difference between COVID-19 and community acquired pneumonia (CAP). Inspired by our findings, DeepSC-COVID is designed with 3 subnets: a cross-task feature subnet for feature extraction, a 3D lesion subnet for lesion segmentation, and a classification subnet for disease diagnosis. Besides, the task-aware loss is proposed for learning the task interaction across the 3D lesion and classification subnets. Different from all existing models for COVID-19 diagnosis, our model is interpretable with fine-grained 3D lesion distribution. Finally, extensive experimental results show that the joint learning framework in our model significantly improves the performance of 3D lesion segmentation and disease classification in both efficiency and efficacy.
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http://dx.doi.org/10.1109/TMI.2021.3079709DOI Listing
September 2021

Lipid-Polymer Hybrid Nanoparticles Enhance the Potency of Ampicillin against in a Protozoa Infection Model.

ACS Infect Dis 2021 06 19;7(6):1607-1618. Epub 2021 Apr 19.

Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551.

() biofilms are implicated in endocarditis, urinary tract infections, and biliary tract infections. Coupled with internalization into host cells, this opportunistic pathogen poses great challenges to conventional antibiotic therapy. The inability of ampicillin (Amp) to eradicate bacteria hidden in biofilms and intracellular niches greatly reduces its efficacy against complicated infections. To enhance the potency of Amp against different forms of infections, Amp was loaded into Lipid-Polymer hybrid Nanoparticles (LPNs), a highly efficient nano delivery platform consisting of a unique combination of DOTAP lipid shell and PLGA polymeric core. The antibacterial activity of these nanoparticles (Amp-LPNs) was investigated in a protozoa infection model, achieving a much higher multiplicity of infection (MOI) compared with studies using animal phagocytes. A significant reduction of total was observed in all groups receiving 250 μg/mL Amp-LPNs compared with groups receiving the same concentration of free Amp during three different interventions, simulating acute and chronic infections and prophylaxis. In early intervention, no viable was observed after 3 h LPNs treatment whereas free Amp did not clear after 24 h treatment. Amp-LPNs also greatly enhanced the antibacterial activity of Amp at late intervention and boosted the survival rate of protozoa approaching 400%, where no viable protozoa were identified in the free Amp groups at the 40 h postinfection treatment time point. Prophylactic effectiveness with Amp-LPNs at a concentration of 250 μg/mL was exhibited in both bacteria elimination and protozoa survival toward subsequent infections. Using protozoa as a surrogate model for animal phagocytes to study high MOI infections, this study suggests that LPN-formulated antibiotics hold the potential to significantly improve the therapeutic outcome in highly complicated bacterial infections.
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http://dx.doi.org/10.1021/acsinfecdis.0c00774DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383308PMC
June 2021

Systemic Inflammatory Markers of Resectable Colorectal Cancer Patients with Different Mismatch Repair Gene Status.

Cancer Manag Res 2021 30;13:2925-2935. Epub 2021 Mar 30.

Department of Hepato-Pancreato-Biliary & Gastric Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang Province, 310022, People's Republic of China.

Background: We aimed to assess the differences in gene expression and systemic inflammatory markers in colorectal cancer (CRC) patients with different mismatch repair (MMR) statuses.

Methods: Bioinformatics analysis was used to identify the different expression genes in patients with CRC at different MMR statuses. A total of 208 patients with resectable colorectal cancer, including 104 deficient mismatch repair (dMMR) patients and 104 matched proficient mismatch repair (pMMR) patients, were retrospectively analyzed.

Results: Bioinformatics analysis showed that chemokine-mediated signaling pathway and inflammatory responses were the main differences in gene expression between dMMR and pMMR CRC patients. In all 208 patients with CRC, those with dMMR frequently had it located on the right side, with more mucinous adenocarcinoma and grade 3 tumors. Patients with dMMR had an earlier American Joint Committee on Cancer (AJCC) stage than pMMR patients. Meanwhile, lymph nodes (LNs) metastasis was more frequently negative in dMMR patients than pMMR patients. Interestingly, patients with CRC with dMMR had more regional lymph nodes removed during surgery, although with less metastatic cancer. Patients with resectable CRC with dMMR were more likely to have higher levels of neutrophil, monocyte, platelet, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), C-reactive protein to albumin ratio (CAR), Glasgow prognostic score (GPS) and C-reactive protein (CRP). In patients with dMMR, those with higher levels of PLR, MLR, CAR, and co-effect present had shorter overall survival (OS) significantly. It was noteworthy that the prognosis of high levels of systemic inflammatory markers did not predict prolonged OS in patients with pMMR CRC.

Conclusion: dMMR CRC has presented a comprehensively distinct systemic inflammatory microenvironment. The systemic inflammatory response can predict oncological outcomes in patients with CRC with dMMR.
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http://dx.doi.org/10.2147/CMAR.S298885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019618PMC
March 2021

Upregulation of Matrix Metalloproteinase-9 Protects against Sepsis-Induced Acute Lung Injury via Promoting the Release of Soluble Receptor for Advanced Glycation End Products.

Oxid Med Cell Longev 2021 10;2021:8889313. Epub 2021 Feb 10.

School of Kinesiology, The Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai 200438, China.

Dysregulation of matrix metalloproteinase- (MMP-) 9 is implicated in the pathogenesis of acute lung injury (ALI). However, it remains controversial whether MMP-9 improves or deteriorates acute lung injury of different etiologies. The receptor for advanced glycation end products (RAGE) plays a critical role in the pathogenesis of acute lung injury. MMPs are known to mediate RAGE shedding and release of soluble RAGE (sRAGE), which can act as a decoy receptor by competitively inhibiting the binding of RAGE ligands to RAGE. Therefore, this study is aimed at clarifying whether and how pulmonary knockdown of MMP-9 affected sepsis-induced acute lung injury as well as the release of sRAGE in a murine cecal ligation and puncture (CLP) model. The analysis of GEO mouse sepsis datasets GSE15379, GSE52474, and GSE60088 revealed that the mRNA expression of MMP-9 was significantly upregulated in septic mouse lung tissues. Elevation of pulmonary MMP-9 mRNA and protein expressions was confirmed in CLP-induced mouse sepsis model. Intratracheal injection of MMP-9 siRNA resulted in an approximately 60% decrease in pulmonary MMP-9 expression. It was found that pulmonary knockdown of MMP-9 significantly increased mortality of sepsis and exacerbated sepsis-associated acute lung injury. Pulmonary MMP-9 knockdown also decreased sRAGE release and enhanced sepsis-induced activation of the RAGE/nuclear factor-B (NF-B) signaling pathway, meanwhile aggravating sepsis-induced oxidative stress and inflammation in lung tissues. In addition, administration of recombinant sRAGE protein suppressed the activation of the RAGE/NF-B signaling pathway and ameliorated pulmonary oxidative stress, inflammation, and lung injury in CLP-induced septic mice. In conclusion, our data indicate that MMP-9-mediated RAGE shedding limits the severity of sepsis-associated pulmonary edema, inflammation, oxidative stress, and lung injury by suppressing the RAGE/NF-B signaling pathway via the decoy receptor activities of sRAGE. MMP-9-mediated sRAGE production may serve as a self-limiting mechanism to control and resolve excessive inflammation and oxidative stress in the lung during sepsis.
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http://dx.doi.org/10.1155/2021/8889313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889353PMC
September 2021

Elevated angiotensin II induces platelet apoptosis through promoting oxidative stress in an AT1R-dependent manner during sepsis.

J Cell Mol Med 2021 04 23;25(8):4124-4135. Epub 2021 Feb 23.

Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Thrombocytopenia is independently related with increased mortality in severe septic patients. Renin-angiotensin system (RAS) is elevated in septic subjects; accumulating studies show that angiotensin II (Ang II) stimulate the intrinsic apoptosis pathway by promoting reactive oxygen species (ROS) production. However, the mechanisms underlying the relationship of platelet apoptosis and RAS system in sepsis have not been fully elucidated. The present study aimed to elucidate whether the RAS was involved in the pathogenesis of sepsis-associated thrombocytopenia and explore the underlying mechanisms. We found that elevated plasma Ang II was associated with decreased platelet count in both patients with sepsis and experimental animals exposed to lipopolysaccharide (LPS). Besides, Ang II treatment induced platelet apoptosis in a concentration-dependent manner in primary isolated platelets, which was blocked by angiotensin II type 1 receptor (AT1R) antagonist losartan, but not by angiotensin II type 2 receptor (AT2R) antagonist PD123319. Moreover, inhibiting AT1R by losartan attenuated LPS-induced platelet apoptosis and alleviated sepsis-associated thrombocytopenia. Furthermore, Ang II treatment induced oxidative stress level in a concentration-dependent manner in primary isolated platelets, which was partially reversed by the AT1R antagonist losartan. The present study demonstrated that elevated Ang II directly stimulated platelet apoptosis through promoting oxidative stress in an AT1R-dependent manner in sepsis-associated thrombocytopenia. The results would helpful for understanding the role of RAS system in sepsis-associated thrombocytopenia.
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http://dx.doi.org/10.1111/jcmm.16382DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051711PMC
April 2021

1-O-Hexyl-2,3,5-Trimethylhydroquinone Ameliorates the Development of Preeclampsia through Suppression of Oxidative Stress and Endothelial Cell Apoptosis.

Oxid Med Cell Longev 2021 15;2021:8839394. Epub 2021 Jan 15.

Department of Obstetrics and Gynecology, Qilu Hospital, Cheeloo College of Medicine, Shangdong University, Jinan, Shangdong 250012, China.

1-O-Hexyl-2,3,5-trimethylhydroquinone (HTHQ), a potent nuclear factor-E2-related factor 2 (Nrf2) activator, has potent antioxidant activity by scavenging reactive oxygen species (ROS). However, the role of HTHQ on the development of preeclampsia (PE) and the underlying mechanisms have barely been explored. In the present study, PE model was induced by adenovirus-mediated overexpression of soluble fms-like tyrosine kinase 1 (sFlt-1) in pregnant mice. The results showed that HTHQ treatment significantly relieved the high systolic blood pressure (SBP) and proteinuria and increased the fetal weight and fetal weight/placenta weight in preeclamptic mice. Furthermore, we found that HTHQ treatment significantly decreased soluble endoglin (sEng), endothelin-1 (ET-1), and activin A and restored vascular endothelial growth factor (VEGF) in preeclamptic mice. In addition, HTHQ treatment inhibited oxidative stress and endothelial cell apoptosis by increasing the levels of Nrf2 and its downstream haemoxygenase-1 (HO-1) protein. In line with the data in vivo, we discovered that HTHQ treatment attenuated oxidative stress and cell apoptosis in human umbilical vein endothelial cells (HUVECs) following hypoxia and reperfusion (H/R), and the HTHQ-mediated protection was lost after transfected with siNrf2. In conclusion, these results suggested that HTHQ ameliorates the development of preeclampsia through suppression of oxidative stress and endothelial cell apoptosis.
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http://dx.doi.org/10.1155/2021/8839394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840260PMC
September 2021

A Genome-Wide Association Study of Childhood Body Fatness.

Obesity (Silver Spring) 2021 02;29(2):446-453

Department of Epidemiology, University of Washington, Seattle, Washington, USA.

Objective: This study aimed to uncover genetic contributors to adiposity in early life.

Methods: A genome-wide association study of childhood body fatness in 34,401 individuals within the Nurses' Health Studies and the Health Professionals Follow-up Study was conducted. Data were imputed to the 1000 Genomes Phase 3 version 5 reference panel.

Results: A total of 1,354 single-nucleotide polymorphisms (P < 10 ) were selected for replication in a previously published genome-wide association study of childhood BMI. Nineteen significant genome-wide (P < 5 × 10 ) regions were observed, fourteen of which were previously associated with childhood obesity and five were novel: BNDF (P = 7.58 × 10 ), PRKD1 (P = 1.43 × 10 ), 20p13 (P = 2.05 × 10 ), FHIT (P = 1.77 × 10 ), and LOC101927575 (P = 3.22 × 10 ). The BNDF, FHIT, and PRKD1 regions were previously associated with adult BMI. LOC101927575 and 20p13 regions have not previously been associated with adiposity phenotypes. In a transcriptome-wide analysis, associations for POMC at 2p23.3 (P = 3.36 × 10 ) and with TMEM18 at 2p25.3 (P = 3.53 × 10 ) were observed. Childhood body fatness was genetically correlated with hip (r = 0.42, P = 4.44 × 10 ) and waist circumference (r = 0.39, P = 5.56 × 10 ), as well as age at menarche (r = -0.37, P = 7.96 × 10 ).

Conclusions: Additional loci that contribute to childhood adiposity were identified, further explicating its genetic architecture.
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http://dx.doi.org/10.1002/oby.23070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7842657PMC
February 2021

The Adrenal Cortex, an Underestimated Site of SARS-CoV-2 Infection.

Front Endocrinol (Lausanne) 2020 8;11:593179. Epub 2021 Jan 8.

Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: The majority of the critically ill patients may have critical illness-related corticosteroid insufficiency (CIRCI). The therapeutic effect of dexamethasone may be related to its ability to improve cortical function. Recent study showed that dexamethasone can reduce COVID-19 deaths by up to one third in critically ill patients. The aim of this article is to investigate whether SARS-CoV-2 can attack the adrenal cortex to aggravate the relative adrenal insufficiency.

Methods: We summarized the clinical features of COVID-19 reported in currently available observational studies. ACE2 and TMPRSS2 expression was examined in human adrenal glands by immunohistochemical staining. We retrospectively analyzed serum cortisol levels in critically ill patients with or without COVID-19.

Results: High percentage of critically ill patients with SARS-COV-2 infection in the study were treated with vasopressors. ACE2 receptor and TMPRSS2 serine protease were colocalized in adrenocortical cells in zona fasciculata and zona reticularis. We collected plasma cortisol concentrations in nine critically ill patients with COVID-19. The cortisol levels of critically ill patients with COVID-19 were lower than those in non-COVID-19 critically ill group. Six of the nine COVID-19 critically ill patients had random plasma cortisol concentrations below 10 µg/dl, which met the criteria for the diagnosis of CIRCI.

Conclusion: We demonstrate that ACE2 and TMPRSS2 are colocalized in adrenocortical cells, and that the cortisol levels are lower in critically ill patients with COVID-19 as compared to those of non-COVID-19 critically ill patients. Based on our findings, we recommend measuring plasma cortisol level to guide hormonal therapy.
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http://dx.doi.org/10.3389/fendo.2020.593179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7820749PMC
January 2021

DRD1 downregulation contributes to mechanical stretch-induced lung endothelial barrier dysfunction.

Theranostics 2021 1;11(6):2505-2521. Epub 2021 Jan 1.

Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.

The lung-protective effects of dopamine and its role in the pathology of ventilator-induced lung injury (VILI) are emerging. However, the underlying mechanisms are still largely unknown. To investigate the contribution of dopamine receptor dysregulation in the pathogenesis of VILI and therapeutic potential of dopamine D1 receptor (DRD1) agonist in VILI. The role of dopamine receptors in mechanical stretch-induced endothelial barrier dysfunction and lung injury was studied in DRD1 knockout mice, in isolated mouse lung vascular endothelial cells (MLVECs), and in lung samples from patients who underwent pulmonary lobectomy with mechanical ventilation for different time periods. DRD1 was downregulated in both surgical patients and mice exposed to mechanical ventilation. Prophylactic administration of dopamine or DRD1 agonist attenuated mechanical stretch-induced lung endothelial barrier dysfunction and lung injury. By contrast, pulmonary knockdown or global knockout of DRD1 exacerbated these effects. Prophylactic administration of dopamine attenuated mechanical stretch-induced α-tubulin deacetylation and subsequent endothelial hyperpermeability through DRD1 signaling. We identified that cyclic stretch-induced glycogen-synthase-kinase-3β activation led to phosphorylation and activation of histone deacetylase 6 (HDAC6), which resulted in deacetylation of α-tubulin. Upon activation, DRD1 signaling attenuated mechanical stretch-induced α-tubulin deacetylation and subsequent lung endothelial barrier dysfunction through cAMP/exchange protein activated by cAMP (EPAC)-mediated inactivation of HDAC6. This work identifies a novel protective role for DRD1 against mechanical stretch-induced lung endothelial barrier dysfunction and lung injury. Further study of the mechanisms involving DRD1 in the regulation of microtubule stability and interference with DRD1/cAMP/EPAC/HDAC6 signaling may provide insight into therapeutic approaches for VILI.
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http://dx.doi.org/10.7150/thno.46192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806475PMC
July 2021

A Hierarchical Approach Using Marginal Summary Statistics for Multiple Intermediates in a Mendelian Randomization or Transcriptome Analysis.

Am J Epidemiol 2021 06;190(6):1148-1158

Previous research has demonstrated the usefulness of hierarchical modeling for incorporating a flexible array of prior information in genetic association studies. When this prior information consists of estimates from association analyses of single-nucleotide polymorphisms (SNP)-intermediate or SNP-gene expression, a hierarchical model is equivalent to a 2-stage instrumental or transcriptome-wide association study (TWAS) analysis, respectively. We propose to extend our previous approach for the joint analysis of marginal summary statistics to incorporate prior information via a hierarchical model (hJAM). In this framework, the use of appropriate estimates as prior information yields an analysis similar to Mendelian randomization (MR) and TWAS approaches. hJAM is applicable to multiple correlated SNPs and intermediates to yield conditional estimates for the intermediates on the outcome, thus providing advantages over alternative approaches. We investigated the performance of hJAM in comparison with existing MR and TWAS approaches and demonstrated that hJAM yields an unbiased estimate, maintains correct type-I error, and has increased power across extensive simulations. We applied hJAM to 2 examples: estimating the causal effects of body mass index (GIANT Consortium) and type 2 diabetes (DIAGRAM data set, GERA Cohort, and UK Biobank) on myocardial infarction (UK Biobank) and estimating the causal effects of the expressions of the genes for nuclear casein kinase and cyclin dependent kinase substrate 1 and peptidase M20 domain containing 1 on the risk of prostate cancer (PRACTICAL and GTEx).
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http://dx.doi.org/10.1093/aje/kwaa287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521785PMC
June 2021

Pinocembrin Inhibits the Proliferation, Migration, Invasiveness, and Epithelial-Mesenchymal Transition of Colorectal Cancer Cells by Regulating LACTB.

Cancer Biother Radiopharm 2020 Dec 31. Epub 2020 Dec 31.

Department of Colorectal Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.

Colorectal cancer (CRC) is a common malignancy of digestive tract. Pinocembrin (PINO) has been discovered to have proapoptotic effect on CRC. This study aimed to elucidate how other biological behaviors of CRC cells were affected under PINO treatment. The effect of PINO on HT29 and HCT116 cells were detected through treatment of different concentrations of PINO. The role of LACTB in PINO treatment was investigated by transfection of siRNA-LACTB. Cell counting kit-8 assay, wound healing assay, and Transwell assay were conducted to evaluate the proliferation, migration, and invasiveness of CRC cells, respectively. Western blot or quantitative reverse transcription-polymerase chain reaction was carried out to measure the expressions of LACTB, matrix metalloproteinase (MMP)-2, E-cadherin, and N-cadherin. Gradient PINO inhibited the viability, migration, invasiveness, and expressions of MMP-2 and N-cadherin in CRC cells, while promoted E-cadherin and LACTB expressions. Silencing LACTB promoted the viability, migration, invasiveness, and expressions of MMP-2 and N-cadherin in CRC cells and inhibited E-cadherin expression. PINO counteracted the effect of silenced LACTB, and yet silencing LACTB partially abolished the effect of PINO on CRC cells. PINO inhibited the proliferation, migration, invasiveness, and epithelial-to-mesenchymal transition of CRC cells by regulating LACTB.
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http://dx.doi.org/10.1089/cbr.2020.4052DOI Listing
December 2020

Neuropsychiatric symptoms are early indicators of an upcoming metabolic decline in Alzheimer's disease.

Transl Neurodegener 2021 01 4;10(1). Epub 2021 Jan 4.

Alzheimer's Disease Research Unit, McGill Centre for Studies in Aging, McGill University, Montréal, Québec, Canada.

Background: Neuropsychiatric symptoms (NPS) are increasingly recognized as early non-cognitive manifestations in the Alzheimer's disease (AD) continuum. However, the role of NPS as an early marker of pathophysiological progression in AD remains unclear. Dominantly inherited AD (DIAD) mutation carriers are young individuals who are destined to develop AD in future due to the full penetrance of the genetic mutation. Hence, the study of DIAD mutation carriers enables the evaluation of the associations between pure AD pathophysiology and metabolic correlates of NPS without the confounding effects of co-existing pathologies. In this longitudinal study, we aimed to identify regional brain metabolic dysfunctions associated with NPS in cognitively intact DIAD mutation carriers.

Methods: We stratified 221 cognitively intact participants from the Dominantly Inherited Alzheimer's Network according to their mutation carrier status. The interactions of NPS measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q), age, and estimated years to symptom onset (EYO) as a function of metabolism measured by [F]flurodeoxyglucose ([F]FDG) positron emission tomography, were evaluated by the mixed-effects regression model with family-level random effects in DIAD mutation carriers and non-carriers. Exploratory factor analysis was performed to identify the neuropsychiatric subsyndromes in DIAD mutation carriers using the NPI-Q sub-components. Then the effects of interactions between specific neuropsychiatric subsyndromes and EYO on metabolism were evaluated with the mixed-effects regression model.

Results: A total of 119 mutation carriers and 102 non-carriers were studied. The interaction of higher NPI-Q and shorter EYO was associated with more rapid declines of global and regional [F]FDG uptake in the posterior cingulate and ventromedial prefrontal cortices, the bilateral parietal lobes and the right insula in DIAD mutation carriers. The neuropsychiatric subsyndromes of agitation, disinhibition, irritability and depression interacted with the EYO to drive the [F]FDG uptake decline in the DIAD mutation carriers. The interaction of NPI and EYO was not associated with [F]FDG uptake in DIAD mutation non-carriers.

Conclusions: The NPS in cognitively intact DIAD mutation carriers may be a clinical indicator of subsequent metabolic decline in brain networks vulnerable to AD, which supports the emerging conceptual framework that NPS represent early manifestations of neuronal injury in AD. Further studies using different methodological approaches to identify NPS in preclinical AD are needed to validate our findings.
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http://dx.doi.org/10.1186/s40035-020-00225-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780680PMC
January 2021

Estimation of COVID-19 risk-stratified epidemiological parameters and policy implications for Los Angeles County through an integrated risk and stochastic epidemiological model.

medRxiv 2020 Dec 14. Epub 2020 Dec 14.

Background: Health disparities have emerged with the COVID-19 epidemic because the risk of exposure to infection and the prevalence of risk factors for severe outcomes given infection vary within and between populations. However, estimated epidemic quantities such as rates of severe illness and death, the case fatality rate (CFR), and infection fatality rate (IFR), are often expressed in terms of aggregated population-level estimates due to the lack of epidemiological data at the refined subpopulation level. For public health policy makers to better address the pandemic, stratified estimates are necessary to investigate the potential outcomes of policy scenarios targeting specific subpopulations.

Methods: We develop a framework for using available data on the prevalence of COVID-19 risk factors (age, comorbidities, BMI, smoking status) in subpopulations, and epidemic dynamics at the population level and stratified by age, to estimate subpopulation-stratified probabilities of severe illness and the CFR (as deaths over observed infections) and IFR (as deaths over estimated total infections) across risk profiles representing all combinations of risk factors including age, comorbidities, obesity class, and smoking status. A dynamic epidemic model is integrated with a relative risk model to produce time-varying subpopulation-stratified estimates. The integrated model is used to analyze dynamic outcomes and parameters by population and subpopulation, and to simulate alternate policy scenarios that protect specific at-risk subpopulations or modify the population-wide transmission rate. The model is calibrated to data from the Los Angeles County population during the period March 1 - October 15 2020.

Findings: We estimate a rate of 0.23 (95% CI: 0.13,0.33) of infections observed before April 15, which increased over the epidemic course to 0.41 (0.11,0.69). Overall population-average IFR( ) estimates for LAC peaked at 0.77% (0.38%,1.15%) on May 15 and decreased to 0.55% (0.24%,0.90%) by October 15. The population-average IFR( ) stratified by age group varied extensively across subprofiles representing each combination of the additional risk factors considered (comorbidities, BMI, smoking). We found median IFRs ranging from 0.009%-0.04% in the youngest age group (0-19), from 0.1%-1.8% for those aged 20-44, 0.36%-4.3% for those aged 45-64, and 1.02%-5.42% for those aged 65+. In the group aged 65+ for which the rate of unobserved infections is likely much lower, we find median CFRs in the range 4.4%-23.45%. The initial societal lockdown period avoided overwhelming healthcare capacity and greatly reduced the observed death count. In comparative scenario analysis, alternative policies in which the population-wide transmission rate is reduced to a moderate and sustainable level of non-pharmaceutical interventions (NPIs) would not have been sufficient to avoid overwhelming healthcare capacity, and additionally would have exceeded the observed death count. Combining the moderate NPI policy with stringent protection of the at-risk subpopulation of individuals 65+ would have resulted in a death count similar to observed levels, but hospital counts would have approached capacity limits.

Interpretation: The risk of severe illness and death of COVID-19 varies tremendously across subpopulations and over time, suggesting that it is inappropriate to summarize epidemiological parameters for the entire population and epidemic time period. This includes variation not only across age groups, but also within age categories combined with other risk factors analyzed in this study (comorbidities, obesity status, smoking). In the policy analysis accounting for differences in IFR across risk groups in comparing the control of infections and protection of higher risk groups, we find that the strict initial lockdown period in LAC was effective because it both reduced overall transmission and protected individuals at greater risk, resulting in preventing both healthcare overload and deaths. While similar numbers of deaths as observed in LAC could have been achieved with a more moderate NPI policy combined with greater protection of individuals 65+, this would have come at the expense of overwhelming the healthcare system. In anticipation of a continued rise in cases in LAC this winter, policy makers need to consider the trade offs of various policy options on the numbers of the overall population that may become infected, severely ill, and that die when considering policies targeted at subpopulations at greatest risk of transmitting infection and at greatest risk for developing severe outcomes.
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http://dx.doi.org/10.1101/2020.12.11.20209627DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756248PMC
December 2020

Efficient replacement of long DNA fragments via non-homologous end joining at non-coding regions.

J Mol Cell Biol 2021 04;13(1):75-77

Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Shanghai Research Center for Brain Science and Brain-Inspired Intelligence, Chinese Academy of Sciences, Shanghai 200031, China.

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http://dx.doi.org/10.1093/jmcb/mjaa051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035993PMC
April 2021

Viewport-based CNN: A Multi-task Approach for Assessing 360° Video Quality.

IEEE Trans Pattern Anal Mach Intell 2020 Oct 5;PP. Epub 2020 Oct 5.

For 360° video, the existing visual quality assessment (VQA) approaches are designed based on either the whole frames or the cropped patches, ignoring the fact that subjects can only access viewports. When watching 360° video, subjects select viewports through head movement (HM) and then fixate on attractive regions within the viewports through eye movement (EM). Therefore, this paper proposes a two-staged multi-task approach for viewport-based VQA on 360° video. Specifically, we first establish a large-scale VQA dataset of 360° video, called VQA-ODV, which collects the subjective quality scores and the HM and EM data on 600 video sequences. By mining our dataset, we find that the subjective quality of 360° video is related to camera motion, viewport positions and saliency within viewports. Accordingly, we propose a viewport-based convolutional neural network (V-CNN) approach for VQA on 360° video, which has a novel multi-task architecture composed of a viewport proposal network (VP-net) and viewport quality network (VQ-net). The VP-net handles the auxiliary tasks of camera motion detection and viewport proposal, while the VQ-net accomplishes the auxiliary task of viewport saliency prediction and the main task of VQA. The experiments validate that our V-CNN approach significantly advances state-of-the-art VQA performance on 360° video and it is also effective in the three auxiliary tasks.
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http://dx.doi.org/10.1109/TPAMI.2020.3028509DOI Listing
October 2020

Potential mechanism and key genes involved in mechanical ventilation and lipopolysaccharide‑induced acute lung injury.

Mol Med Rep 2020 Nov 14;22(5):4265-4277. Epub 2020 Sep 14.

Department of Anesthesiology and Surgical Intensive Care Unit, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China.

Mechanical ventilation (MV) and lipopolysaccharide (LPS) infection are common causes of acute lung injury. The aim of the present study was to identify the key genes and potential mechanisms involved in mechanical ventilation (MV) and lipopolysaccharide (LPS)‑induced acute lung injury (ALI). Gene expression data of adult C57BL/6 mice with ALI induced by inhaling LPS, MV and LPS + MV were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) associated with MV, LPS and LPS + MV were screened, followed by functional enrichment analysis, protein‑protein interaction network construction, and prediction of transcription factors and small molecule drugs. Finally, the expression of key genes was verified in vivo using reverse transcription‑quantitative PCR. A total of 63, 538 and 1,635 DEGs were associated with MV, LPS and LPS + MV, respectively. MV‑associated genes were significantly enriched in the 'purine ribonucleotide metabolic process'. LPS and LPS + MV‑associated genes were significantly enriched in 'cellular response to cytokine stimulus' and 'cell chemotaxis'. All three conditions were enriched in 'TNF signaling pathway' and 'IL‑17 signaling pathway'. Expression levels of C‑X‑C motif chemokine ligand (CXCL)2, CXCL3 and CXCL10 were upregulated in the LPS and LPS + MV groups. Adenosine A2b receptor, zinc finger and BTB domain‑containing 16 and hydroxycarboxylic acid receptor 2 were identified as DEGs in the MV group. Compared with the control group, Early growth response 1 and activating TF 3 was upregulated in all three groups. Similarities and differences were observed among the MV‑ and LPS‑induced ALI, and MV may enhance the effects of LPS on gene expression. MV may affect urine ribonucleotide metabolic‑related processes, whereas LPS may cause cell chemotaxis and cytokine stimulus responses in ALI progression. The inflammatory response was shared by MV and LPS. The results of the present study may provide insight into a theoretical basis for the study and treatment of ALI.
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http://dx.doi.org/10.3892/mmr.2020.11507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7533521PMC
November 2020

Recognition of atopic keratoconjunctivitis during treatment with dupilumab for atopic dermatitis.

J Am Acad Dermatol 2021 Jul 19;85(1):265-267. Epub 2020 Sep 19.

Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, Iowa. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.09.046DOI Listing
July 2021

Factors affecting airway compliance and resistance in children receiving general anesthesia during adenotonsillectomy.

Medicine (Baltimore) 2020 Sep;99(36):e22101

Department of Anesthesiology, Shanghai Ninth People's Hospital.

Airway compliance is an important index in the surgery of pediatric patients. This study aimed to explore factors affecting dynamic airway compliance (Cdyn) and airway resistance (Raw) after general anesthesia endotracheal intubation for adenotonsillectomy of pediatric patients.A prospective study was undertaken of 107 children who underwent adenotonsillectomy in Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine between January and June 2018. The values of Cdyn and Raw were recorded at 5, 10, and 15 minute during general anesthesia endotracheal intubation. Univariate analysis and multiple linear regression analysis were performed for factors that affected Cdyn and Raw.Of the 107 patients aged 56.67 ± 18.28 months, 69 (64%) patients were male, and 26 (24%) and 12 (11%) had an upper respiratory infection in the past week and 1 to 2 weeks, respectively. During anesthesia, Cdyn showed a decreasing trend (P < .001) while Raw showed an increasing trend (P < .001). Multivariate analysis revealed that height (β=0.177-0.193) had the strongest correlation with Cdyn; rales during pulmonary auscultation (β= -2.727 to -1.363) and sputum suction (β= -1.670 to -0.949) were also associated with Cdyn (all P < .05). Height was the factor with the strongest negative correlation with Raw (β= -0.382 to -0.305). Rales during pulmonary auscultation (β=10.063-11.326) and sputum suction (β=3.863-9.003) were also associated with Raw (All P < .05).Height, rales during preoperative auscultation and sputum suction were all associated with intraoperative Cydn and Raw for pediatric patients undergoing adenotonsillectomy and should be considered before the surgery.
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http://dx.doi.org/10.1097/MD.0000000000022101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478555PMC
September 2020

Conditions that promote the formation of black bloom in aquatic microcosms and its effects on sediment bacteria related to iron and sulfur cycling.

Sci Total Environ 2021 Jan 21;751:141869. Epub 2020 Aug 21.

School of Resources and Environmental Science, Wuhan University, Wuhan 430079, PR China. Electronic address:

Black bloom occurs frequently in eutrophic waters. We investigated the conditions promoted the formation of black bloom via in-situ measurement in two aquatic microcosms and the effects of black bloom on the bacterial community composition. Although larger changes in dissolved oxygen (DO) were detected in the Hydrilla verticillata-dominated microcosm over the 90-day simulation, black bloom occurred more readily in the phytoplankton-dominated than macrophyte-dominated microcosm under conditions of O depletion and temperature above 30 °C. The sediment bacterial community composition shifted after black bloom; the relative abundance of Thiobacillus and Sideroxydans, which oxidize iron (Fe) and sulfur (S), decreased by 47% and 48%, respectively, in the phytoplankton-dominated microcosm and by 18% and 20% in the macrophyte-dominated microcosm. By contrast, Desulfatiglans increased by 13% and 19%, respectively, after black bloom. Furthermore, inter-taxa correlations remarkably changed according to co-occurrence network analysis. Thirty-six different taxa from the phylum to the genus level were identified as biomarkers of sediments collected before and after the black bloom event. Most of these biomarkers are related to Fe/S cycling in aquatic ecosystems.
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http://dx.doi.org/10.1016/j.scitotenv.2020.141869DOI Listing
January 2021

Peroxiredoxin-1 Overexpression Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Oxidative Stress and Cardiomyocyte Apoptosis.

Oxid Med Cell Longev 2020 29;2020:2405135. Epub 2020 Jul 29.

Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.

. Previous research has shown that peroxiredoxin 1 (Prdx1) is an important modulator of physiological and pathophysiological cardiovascular events. This study is aimed at investigating the role and underlying mechanism of Prdx1 in doxorubicin- (DOX-) induced cardiotoxicity. Cardiac-specific expression of Prdx1 was induced in mice, and the mice received a single dose of DOX (15 mg/kg) to generate cardiotoxicity. First, our study demonstrated that Prdx1 expression was upregulated in the heart and in cardiomyocytes after DOX treatment. Second, we provided direct evidence that Prdx1 overexpression ameliorated DOX-induced cardiotoxicity by attenuating oxidative stress and cardiomyocyte apoptosis. Mechanistically, we found that DOX treatment increased the phosphorylation level of apoptosis signal-regulating kinase-1 (ASK1) and the downstream protein p38 in the heart and in cardiomyocytes, and these effects were decreased by Prdx1 overexpression. In contrast, inhibiting Prdx1 promoted DOX-induced cardiac injury via the ASK1/p38 pathway. These results suggest that Prdx1 may be an effective therapeutic option to prevent DOX-induced cardiotoxicity.
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http://dx.doi.org/10.1155/2020/2405135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411498PMC
May 2021

Estimating the effects of copy-number variants on intelligence using hierarchical Bayesian models.

Genet Epidemiol 2020 11 11;44(8):825-840. Epub 2020 Aug 11.

Lady Davis Institute, Jewish General Hospital, Montreal, Canada.

It is challenging to estimate the phenotypic impact of the structural genome changes known as copy-number variations (CNVs), since there are many unique CNVs which are nonrecurrent, and most are too rare to be studied individually. In recent work, we found that CNV-aggregated genomic annotations, that is, specifically the intolerance to mutation as measured by the pLI score (probability of being loss-of-function intolerant), can be strong predictors of intellectual quotient (IQ) loss. However, this aggregation method only estimates the individual CNV effects indirectly. Here, we propose the use of hierarchical Bayesian models to directly estimate individual effects of rare CNVs on measures of intelligence. Annotation information on the impact of major mutations in genomic regions is extracted from genomic databases and used to define prior information for the approach we call HBIQ. We applied HBIQ to the analysis of CNV deletions and duplications from three datasets and identified several genomic regions containing CNVs demonstrating significant deleterious effects on IQ, some of which validate previously known associations. We also show that several CNVs were identified as deleterious by HBIQ even if they have a zero pLI score, and the converse is also true. Furthermore, we show that our new model yields higher out-of-sample concordance (78%) for predicting the consequences of carrying known recurrent CNVs compared with our previous approach.
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http://dx.doi.org/10.1002/gepi.22344DOI Listing
November 2020
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