Publications by authors named "Rong Xu"

693 Publications

Enhancing the differentiation of walking and standing via the ratio of plantar pressures.

Proc Inst Mech Eng H 2021 Dec 6:9544119211058914. Epub 2021 Dec 6.

College of Electronic and Optical Engineering, Nanjing University of Posts and Telecommunications, Nanjing, China.

Differentiation of standing and walking based on plantar pressures is helpful in developing strategies to reduce health risks in the workplace. In order to improve the differentiation ability, the paper proposes a new metric for posture differentiation, that is, the pressure ratio on the two anatomical plantar regions. The plantar pressures were collected from 30 persons during walking and standing. After verifying the normal distribution of the pressure ratio by the Monte Carlo method, two-way repeated-measures ANOVA was conducted for the pressure ratios. The advantage of the pressure ratio over two conventional pressure metrics (the average pressure and the peak pressure) is demonstrated by its much larger size effect. Furthermore, the pressure ratio permits to establish value ranges corresponding to walking and standing, which are less influenced by specific person factors, thus facilitating the design of a standardized posture recognition system. The underlying mechanism underlying the pressure ratio is discussed from the aspect of biomechanics of movement.
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http://dx.doi.org/10.1177/09544119211058914DOI Listing
December 2021

Effective adsorption of zeolite/carbon composite molecular sieve synthesized from spent bleaching earth.

Environ Sci Pollut Res Int 2021 Dec 1. Epub 2021 Dec 1.

Key Laboratory for Soft Chemistry and Functional Materials, Ministry of Education, Nanjing University of Science and Technology, Nanjing, 210094, China.

Spent bleaching earth (SBE) as an industrious solid rubbish seriously causes the environmental pollution problem. The resourceful utilization of SBE has become increasingly important. In this work, silicon and carbon ingredients derived from SBE were coincidently employed to synthesize a 4A zeolite/carbon composite molecular sieve (4A/CMS). Therein, the graphite carbon components in the form of porous lamellar scattering among the interlayer, surface, and periphery of 4A zeolite promote the rate of mass transfer for the lipophilic gas, which can effectively improve the adsorption property for the volatile organic compounds. The obtained 4A/CMS has large specific surface area, hierarchical pore structure, satisfactory adsorption capacity, and regeneration performance, and its equilibrium adsorption capacity of p-xylene can achieve 209.57 mg·g. The pseudo-first-order rate equation is appropriate for the adsorption kinetics. In the end, the formation mechanism of 4A/CMS was illuminated in detail. □ Spent bleaching earth (SBE) as an industrious solid rubbish were utilized resourcefully. Silicon and carbon ingredients from SBE were coincidently employed to synthesize 4A/CMS. Graphitic carbon with hierarchical pore promoted the rate of mass transfer of organic gas. 4A/CMS exhibited excellent adsorption capacity and regeneration performance of p-xylene.
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http://dx.doi.org/10.1007/s11356-021-17552-wDOI Listing
December 2021

Taraxasterol mitigates Con A-induced hepatitis in mice by suppressing interleukin-2 expression and its signaling in T lymphocytes.

Int Immunopharmacol 2021 Nov 27:108380. Epub 2021 Nov 27.

Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China. Electronic address:

Discovery of anti-inflammatory drugs that can suppress T lymphocyte activation and proliferation by inhibiting TCR/CD3 and IL-2/IL-2R signaling is still needed in clinic, though rapamycin and other related reagents have made great success. Taraxasterol (TAS) is an active ingredient of dandelion, an anti-inflammatory medicinal herb with low in vivo toxicity that has long been used in China. Yet the action mechanism of TAS on lymphocytes remains elusive. The anti-inflammatory effects of TAS were evaluated in C57BL/6 mouse primary lymphocytes stimulated with concanavalin A (Con A) in vitro and in mouse model of Con A-induced acute hepatitis in vivo. Our results showed that TAS significantly suppressed Con A-induced acute hepatitis in a mouse model, reducing the hepatic necrosis areas, the release of aminotransferases, and the production of IL-2 and other inflammatory cytokines. Supporting this, in vitro study also showed that TAS reduced the production of IL-2 and the expression of IL-2 receptor subunit α (CD25) upon the stimulation of Con A, which was likely mediated by suppressing NF-κB activation. The downstream pathways of IL-2/IL-2R signaling, including the activation of PI3K/PDK1/mTOR, STAT3 and STAT5, were also suppressed by TAS. Consistently, Con A-induced T cell proliferation was also inhibited by TAS in vitro. Our data indicate that TAS can suppress both T lymphocyte activation and cell proliferation by down-regulating IL-2 expression and its signaling pathway thereby ameliorating Con A-induced acute hepatitis, highlighting TAS as a potential drug candidate for treating inflammatory diseases including autoimmune hepatitis.
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http://dx.doi.org/10.1016/j.intimp.2021.108380DOI Listing
November 2021

Association of left ventricular systolic dysfunction with coronary artery dilation in Kawasaki disease patients: Assessment with cardiovascular magnetic resonance.

Eur J Radiol 2021 Dec 16;145:110039. Epub 2021 Nov 16.

Department of Radiology, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China. Electronic address:

Purpose: To quantify global and regional left ventricular (LV) strain parameters in patients with Kawasaki disease (KD) using cardiovascular magnetic resonance (CMR) tissue tracking and assess the association of coronary artery dilation (CA dilation) with LV systolic dysfunction.

Methods: Thirty-one KD patients with CA dilation, 22 patients without CA dilation and 27 age- and sex-matched normal controls underwent 3.0 T CMR examination. Z score of >2 was defined as CA dilation. Global LV strain parameters and regional LV strain parameters in 16 American Heart Association segmentation, including radial, circumferential and longitudinal peak strain (PS) and LV function were measured and compared among groups.

Results: No significant difference in LV ejection fraction has been observed among controls, KD patients with CA dilation and without CA dilation (all p > 0.05). However, global longitudinal PS (GLPS) was lower in groups with CA dilation than those without CA dilation (-12.6 ± 4.1% vs -14.9 ± 2.6%, p < 0.05). For regional strain parameters, the segments with CA dilation (n = 301) were lower than those in both normal controls (n = 416) and segments without CA dilation (n = 547) in regional radial, circumferential and longitudinal PS (all p < 0.05). The severity of CA dilation was positively correlated to GLPS and regional longitudinal PS (r = 0.388 and r = 0.222; both p < 0.05) in KD patients. After adjusting for clinical characteristics, the multivariate analysis demonstrated that Z score was independently associated with GLPS in KD patients (β = 0.469, p = 0.000, model R = 0.355).

Conclusions: CMR tissue tracking could sensitively identify subclinical LV dysfunction in KD patients with CA dilation. LV systolic dysfunction occurs particularly in the myocardium dominated by the dilated coronary artery. CA dilation is an independent predictor of LV systolic dysfunction.
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http://dx.doi.org/10.1016/j.ejrad.2021.110039DOI Listing
December 2021

Risks of SARS-CoV-2 Breakthrough Infection and Hospitalization in Fully Vaccinated Patients With Multiple Myeloma.

JAMA Netw Open 2021 11 1;4(11):e2137575. Epub 2021 Nov 1.

Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, Ohio.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.37575DOI Listing
November 2021

fIDBAC: A Platform for Fast Bacterial Genome Identification and Typing.

Front Microbiol 2021 18;12:723577. Epub 2021 Oct 18.

Department of Infectious Diseases, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.

To study the contamination of microorganisms in the food industry, pharmaceutical industry, clinical diagnosis, or bacterial taxonomy, accurate identification of species is a key starting point of further investigation. The conventional method of identification by the 16S rDNA gene or other marker gene comparison is not accurate, because it uses a tiny part of the genomic information. The average nucleotide identity calculated between two whole bacterial genomes was proven to be consistent with DNA-DNA hybridization and adopted as the gold standard of bacterial species delineation. Furthermore, there are more bacterial genomes available in public databases recently. All of those contribute to a genome era of bacterial species identification. However, wrongly labeled and low-quality bacterial genome assemblies, especially from type strains, greatly affect accurate identification. In this study, we employed a multi-step strategy to create a type-strain genome database, by removing the wrongly labeled and low-quality genome assemblies. Based on the curated database, a fast bacterial genome identification platform (fIDBAC) was developed (http://fbac.dmicrobe.cn/). The fIDBAC is aimed to provide a single, coherent, and automated workflow for species identification, strain typing, and downstream analysis, such as CDS prediction, drug resistance genes, virulence gene annotation, and phylogenetic analysis.
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http://dx.doi.org/10.3389/fmicb.2021.723577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558511PMC
October 2021

Heterogeneous alterations in thalamic subfields in major depression disorder.

J Affect Disord 2021 12 4;295:1079-1086. Epub 2021 Sep 4.

Key Laboratory for Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China.

Background: It is well known that the thalamus is not a unitary and homogeneous entity but a complex and highly connected archeocortical structure. Although many neuroimaging studies have reported alterations in the thalamus in major depressive disorder (MDD), the structural alterations in thalamic subfields remain unclear. This study aimed to investigate changes in gray matter volume (GMV) in thalamic subfields in MDD patients.

Methods: The present study included structural images of 848 MDD patients and 794 age-matched normal controls (NC) from 17 study sites of the REST-meta-MDD consortium. We performed voxel-based morphometric analyses to calculate the GMV in the entire thalamus and its subfields using three different automated anatomical labeling atlases and subsequently compared the differences between first-episode drug-naïve major depressive disorder (FEDN), recurrent major depressive disorder (RMDD), and NC groups. We also evaluated the relationships between thalamic GMV and clinical symptoms in MDD patients.

Results: Compared to NC, the FEDN patients showed increased GMV in thalamic subfields but not in the entire thalamus, while RMDD patients showed no significant alterations in GMV in the entire thalamus and its subfields. Moreover, the mean GMV in the right anterior thalamus and left anteroventral thalamus in RMDD patients were mildly positively correlated with the Hamilton Anxiety Rating Scale scores.

Limitations: The main limitations are a single-modal analysis based on T1-weighted MR images and a cross-sectional design.

Conclusions: Our findings suggest that FEDN and RMDD patients show heterogeneous alterations across thalamic subfields, which may help us understand the pathophysiological mechanisms of MDD.
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http://dx.doi.org/10.1016/j.jad.2021.08.115DOI Listing
December 2021

All-Solid-State Lithium-Sulfur Batteries Enhanced by Redox Mediators.

J Am Chem Soc 2021 Nov 22;143(43):18188-18195. Epub 2021 Oct 22.

Department of Materials Science and Engineering, Stanford University, Stanford, California 94305, United States.

Redox mediators (RMs) play a vital role in some liquid electrolyte-based electrochemical energy storage systems. However, the concept of redox mediator in solid-state batteries remains unexplored. Here, we selected a group of RM candidates and investigated their behaviors and roles in all-solid-state lithium-sulfur batteries (ASSLSBs). The soluble-type quinone-based RM (AQT) shows the most favorable redox potential and the best redox reversibility that functions well for lithium sulfide (LiS) oxidation in solid polymer electrolytes. Accordingly, LiS cathodes with AQT RMs present a significantly reduced energy barrier (average oxidation potential of 2.4 V) during initial charging at 0.1 C at 60 °C and the following discharge capacity of 1133 mAh g. Using sulfur K-edge X-ray absorption spectroscopy, we directly tracked the sulfur speciation in ASSLSBs and proved that the solid-polysulfide-solid reaction of LiS cathodes with RMs facilitated LiS oxidation. In contrast, for bare LiS cathodes, the solid-solid LiS-sulfur direct conversion in the first charge cycle results in a high energy barrier for activation (charge to ∼4 V) and low sulfur utilization. The [email protected] cell demonstrates superior cycling stability (average Coulombic efficiency 98.9% for 150 cycles) and rate capability owing to the effective AQT-enhanced Li-S reaction kinetics. This work reveals the evolution of sulfur species in ASSLSBs and realizes the fast Li-S reaction kinetics by designing an effective sulfur speciation pathway.
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http://dx.doi.org/10.1021/jacs.1c07754DOI Listing
November 2021

Kir6.2 is essential to maintain neurite features by modulating PM20D1-reduced mitochondrial ATP generation.

Redox Biol 2021 11 15;47:102168. Epub 2021 Oct 15.

Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, Nanjing, 211166, China; Neuroprotective Drug Discovery Key Laboratory, Department of Pharmacology, Nanjing Medical University, Nanjing, 211166, China. Electronic address:

Kir6.2, a pore-forming subunit of the ATP-sensitive potassium (KATP) channels, regulates the functions of metabolically active tissues and acts as an ideal therapeutic target for multiple diseases. Previous studies have been conducted on peripheral kir6.2, but its precise physiological roles in the central nervous system (CNS) have rarely been revealed. In the current study, we evaluated the neurophenotypes and neuroethology of kir6.2 knockout (kir6.2) mice. We demonstrated the beneficial effects of kir6.2 on maintaining the morphology of mesencephalic neurons and controlling the motor coordination of mice. The mechanisms underlying the abnormal neurological features of kir6.2 deficiency were analyzed by RNA sequencing (RNA-seq). Pm20d1, a gene encoding PM20D1 secretase that promotes the generation of endogenous mitochondria uncouplers in vivo, was dramatically upregulated in the midbrain of kir6.2 mice. Further investigations verified that PM20D1-induced increase of N-acyl amino acids (N-AAAs) from circulating fatty acids and amino acids promoted mitochondrial impairments and cut down the ATP generation, which mediated the morphological defects of the mesencephalic neurons and thus led to the behavioral impairments of kir6.2 knockout mice. This study is the first evidence to demonstrate the roles of kir6.2 in the morphological maintenance of neurite and motor coordination control of mice, which extends our understanding of kir6.2/KATP channels in regulating the neurophysiological function.
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http://dx.doi.org/10.1016/j.redox.2021.102168DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8577462PMC
November 2021

Gut-microbiota-microglia-brain interactions in Alzheimer's disease: knowledge-based, multi-dimensional characterization.

Alzheimers Res Ther 2021 10 20;13(1):177. Epub 2021 Oct 20.

Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, 2103 Cornell Rd, Cleveland, OH, 44106, USA.

Background: Interactions between the gut microbiota, microglia, and aging may modulate Alzheimer's disease (AD) pathogenesis but the precise nature of such interactions is not known.

Methods: We developed an integrated multi-dimensional, knowledge-driven, systems approach to identify interactions among microbial metabolites, microglia, and AD. Publicly available datasets were repurposed to create a multi-dimensional knowledge-driven pipeline consisting of an integrated network of microbial metabolite-gene-pathway-phenotype (MGPPN) consisting of 34,509 nodes (216 microbial metabolites, 22,982 genes, 1329 pathways, 9982 mouse phenotypes) and 1,032,942 edges.

Results: We evaluated the network-based ranking algorithm by showing that abnormal microglia function and physiology are significantly associated with AD pathology at both genetic and phenotypic levels: AD risk genes were ranked at the top 6.4% among 22,982 genes, P < 0.001. AD phenotypes were ranked at the top 11.5% among 9982 phenotypes, P < 0.001. A total of 8094 microglia-microbial metabolite-gene-pathway-phenotype-AD interactions were identified for top-ranked AD-associated microbial metabolites. Short-chain fatty acids (SCFAs) were ranked at the top among prioritized AD-associated microbial metabolites. Through data-driven analyses, we provided evidence that SCFAs are involved in microglia-mediated gut-microbiota-brain interactions in AD at both genetic, functional, and phenotypic levels.

Conclusion: Our analysis produces a novel framework to offer insights into the mechanistic links between gut microbial metabolites, microglia, and AD, with the overall goal to facilitate disease mechanism understanding, therapeutic target identification, and designing confirmatory experimental studies.
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http://dx.doi.org/10.1186/s13195-021-00917-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8529734PMC
October 2021

Downregulation of HOXC6 by miR-27a ameliorates gefitinib resistance in non-small cell lung cancer.

Am J Cancer Res 2021 15;11(9):4329-4346. Epub 2021 Sep 15.

Department of Pharmacology, School of Basic Medicine, Tongji Medical College of Huazhong University of Science and Technology Wuhan, China.

Non-small cell lung cancer (NSCLC) is a major type of lung cancer. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), represented by gefitinib (Gef), are targeted drugs used for the treatment of NSCLC. However, NSCLC patients often develop resistance to tyrosine kinase inhibitors, which limits their efficacy. Homeobox gene HOXC6 is dysregulated in many cancers and contributes to chemoresistance in cancer cells. However, the role and mechanism of HOXC6 in the development of Gef resistance in NSCLC remains unclear. In the present study, we found that HOXC6 was highly expressed in Gef-resistant NSCLC cells. Further experiments showed that silencing of HOXC6 ameliorated Gef resistance in PC9/G cells whereas overexpression of HOXC6 promoted Gef resistance in PC9 cells. HOXC6 influenced Gef sensitivity in NSCLC cells by regulating cell proliferation, colony formation, cell apoptosis, cell cycle, cell mobility and other related signaling molecules or pathways. HOXC6 was also found to be a direct target of miR-27a. As expected, overexpression of miR-27a ameliorated Gef resistance by inhibiting HOXC6 expression and . Clinical analysis revealed that high HOXC6 levels and low miR-27a levels were significantly correlated with more malignant clinical features and poorer survival of NSCLC patients. In summary, the present study demonstrates that HOXC6 may be a potential therapeutic target for overcoming Gef resistance in NSCLC patients. A combination of Gef and miR-27a agomirs may be an effective intervention for Gef-resistant NSCLC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493406PMC
September 2021

Global, segmental and layer specific analysis of myocardial involvement in Duchenne muscular dystrophy by cardiovascular magnetic resonance native T1 mapping.

J Cardiovasc Magn Reson 2021 10 14;23(1):110. Epub 2021 Oct 14.

Department of Radiology, Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, West China Second University Hospital, Sichuan University, 20# Section 3 South Renmin Road, Chengdu, 610041, China.

Background: Progressive cardiomyopathy accounts for almost all mortality among Duchenne muscular dystrophy (DMD) patients.‍ Thus, our aim was to comprehensively characterize myocardial involvement by investigating the heterogeneity of native T1 mapping in DMD patients using global and regional (including segmental and layer-specific) analysis across a large cohort.

Methods: We prospectively enrolled 99 DMD patients (8.8 ± 2.5 years) and 25 matched male healthy controls (9.5 ± 2.5 years). All subjects underwent cardiovascular magnetic resonance (CMR) with cine, T1 mapping and late gadolinium enhancement (LGE) sequences. Native T1 values based on the global and regional myocardium were measured, and LGE was defined.

Results: LGE was present in 49 (49%) DMD patients. Global native T1 values were significantly longer in LGE-positive (LGE +) patients than in healthy controls, both in basal slices (1304 ± 55 vs. 1246 ± 27 ms, p < 0.001) and in mid-level slices (1305 ± 57 vs. 1245 ± 37 ms, p < 0.001). No significant difference in global native T1 was found between healthy controls and LGE-negative (LGE-) patients. In segmental analysis, LGE + patients had significantly increased native T1 in all analyzed segments compared to the healthy control group. Meanwhile, the comparison between LGE- patients and healthy controls showed significantly elevated values only in the basal anterolateral segment (1273 ± 62 vs. 1234 ± 40 ms, p = 0.034). Interestingly, the epicardial layer had a significantly higher native T1 in LGE- patients than in healthy controls (p < 0.05), whereas no such pattern was noticed in the global myocardium. Epicardial layer native T1 resulted in the highest diagnostic performance for distinguishing between healthy controls and DMD patients in receiver operating curve analyses (area under the curve [AUC] 0.84 for basal level and 0.85 for middle level) when compared to global native T1 and endocardial layer native T1.

Conclusions: Myocardial regional native T1, particularly epicardial native T1, seems to have potential as a novel robust marker of very early cardiac involvement in DMD patients.

Trial Registration: Chinese Clinical Trial Registry ( http://www.chictr.org.cn/index.aspx ) ChiCTR1800018340, 09/12/2018, Retrospectively registered.
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http://dx.doi.org/10.1186/s12968-021-00802-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515679PMC
October 2021

A Morphologically Stable Li/Electrolyte Interface for All-Solid-State Batteries Enabled by 3D-Micropatterned Garnet.

Adv Mater 2021 Oct 10:e2104009. Epub 2021 Oct 10.

Department of Materials Science and Engineering, Stanford University, Stanford, CA, 94305, USA.

Morphological degradation at the Li/solid-state electrolyte (SSE) interface is a prevalent issue causing performance fading of all-solid-state batteries (ASSBs). To maintain the interfacial integrity, most ASSBs are operated under low current density with considerable stack pressure, which significantly limits their widespread usage. Herein, a novel 3D-micropatterned SSE (3D-SSE) that can stabilize the morphology of the Li/SSE interface even under relatively high current density and limited stack pressure is reported. Under the pressure of 1.0 MPa, the Li symmetric cell using a garnet-type 3D-SSE fabricated by laser machining shows a high critical current density of 0.7 mA cm and stable cycling over 500 h under 0.5 mA cm . This excellent performance is attributed to the reduced local current density and amplified mechanical stress at the Li/3D-SSE interface. These two effects can benefit the flux balance between Li stripping and creep at the interface, thereby preventing interfacial degradation such as void formation and dendrite growth.
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http://dx.doi.org/10.1002/adma.202104009DOI Listing
October 2021

Increased risk for COVID-19 breakthrough infection in fully vaccinated patients with substance use disorders in the United States between December 2020 and August 2021.

World Psychiatry 2021 Oct 5. Epub 2021 Oct 5.

Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.

Individuals with substance use disorders (SUDs) are at increased risk for COVID-19 infection and for adverse outcomes of the infection. Though vaccines are highly effective against COVID-19, their effectiveness in individuals with SUDs might be curtailed by compromised immune status and a greater likelihood of exposures, added to the waning vaccine immunity and the new SARS-CoV-2 variants. In a population-based cohort study, we assessed the risk, time trends, outcomes and disparities of COVID-19 breakthrough infection in fully vaccinated SUD patients starting 14 days after completion of vaccination. The study included 579,372 individuals (30,183 with a diagnosis of SUD and 549,189 without such a diagnosis) who were fully vaccinated between December 2020 and August 2021, and had not contracted COVID-19 infection prior to vaccination. We used the TriNetX Analytics network platform to access de-identified electronic health records from 63 health care organizations in the US. Among SUD patients, the risk for breakthrough infection ranged from 6.8% for tobacco use disorder to 7.8% for cannabis use disorder, all significantly higher than the 3.6% in non-SUD population (p<0.001). Breakthrough infection risk remained significantly higher after controlling for demographics (age, gender, ethnicity) and vaccine types for all SUD subtypes, except for tobacco use disorder, and was highest for cocaine and cannabis use disorders (hazard ratio, HR=2.06, 95% CI: 1.30-3.25 for cocaine; HR=1.92, 95% CI: 1.39-2.66 for cannabis). When we matched SUD and non-SUD individuals for lifetime comorbidities and adverse socioeconomic determinants of health, the risk for breakthrough infection no longer differed between these populations, except for patients with cannabis use disorder, who remained at increased risk (HR=1.55, 95% CI: 1.22-1.99). The risk for breakthrough infection was higher in SUD patients who received the Pfizer than the Moderna vaccine (HR=1.49, 95% CI: 1.31-1.69). In the vaccinated SUD population, the risk for hospitalization was 22.5% for the breakthrough cohort and 1.6% for the non-breakthrough cohort (risk ratio, RR=14.4, 95% CI: 10.19-20.42), while the risk for death was 1.7% and 0.5% respectively (RR=3.5, 95% CI: 1.74-7.05). No significant age, gender and ethnic disparities for breakthrough infection were observed in vaccinated SUD patients. These data suggest that fully vaccinated SUD individuals are at higher risk for breakthrough COVID-19 infection, and this is largely due to their higher prevalence of comorbidities and adverse socioeconomic determinants of health compared with non-SUD individuals. The high frequency of comorbidities in SUD patients is also likely to contribute to their high rates of hospitalization and death following breakthrough infection.
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http://dx.doi.org/10.1002/wps.20921DOI Listing
October 2021

Potential long-term effect of tumor necrosis factor inhibitors on dementia risk: A propensity score matched retrospective cohort study in US veterans.

Alzheimers Dement 2021 Sep 27. Epub 2021 Sep 27.

Center for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.

Introduction: Tumor necrosis factor (TNF) inhibitors are widely used to treat rheumatoid arthritis (RA) and their potential to retard Alzheimer's disease (AD) progression has been reported. However, their long-term effects on the dementia/AD risk remain unknown.

Methods: A propensity scored matched retrospective cohort study was conducted among 40,207 patients with RA within the US Veterans Affairs health-care system from 2000 to 2020.

Results: A total of 2510 patients with RA prescribed TNF inhibitors were 1:2 matched to control patients. TNF inhibitor use was associated with reduced dementia risk (hazard ratio [HR]: 0.64, 95% confidence interval [CI]: 0.52-0.80), which was consistent as the study period increased from 5 to 20 years after RA diagnosis. TNF inhibitor use also showed a long-term effect in reducing the risk of AD (HR: 0.57, 95% CI: 0.39-0.83) during the 20 years of follow-up.

Conclusion: TNF inhibitor use is associated with lower long-term risk of dementia/AD among US veterans with RA.
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http://dx.doi.org/10.1002/alz.12465DOI Listing
September 2021

Nursing Interns' Attitudes Toward, Preferences for, and Use of Diabetes Virtual Simulation Teaching Applications in China: National Web-Based Survey.

JMIR Mhealth Uhealth 2021 09 9;9(9):e29498. Epub 2021 Sep 9.

Clinical Nursing Teaching and Research Section, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: Diabetes has placed heavy social and economic burdens on society and families worldwide. Insufficient knowledge and training of frontline medical staff, such as nurses, interns, and residents, may lead to an increase in acute and chronic complications among patients with diabetes. However, interns have insufficient knowledge about diabetes management. The factors that affect interns' current level of diabetes-related knowledge are still unclear. Therefore, understanding the behavioral intentions of interns is essential to supporting the development and promotion of the use of virtual simulation teaching applications.

Objective: This study aimed to identify the determinants of nursing interns' intentions to use simulation-based education applications.

Methods: From December 1, 2020, to February 28, 2021, the web-based survey tool Sojump (Changsha Xingxin Information Technology Co) was used to survey nursing interns in hospitals across China. Two survey links were sent to 37 partner schools in 23 major cities in China, and they were disseminated through participants' WeChat networks. Multiple regression analysis was used to determine the association between demographic information and basic disease information and the use of the application for treating adult patients.

Results: Overall, 883 nursing interns from 23 provinces in China responded to the survey. Among them, the virtual simulation utilization rate was 35.6% (314/883) and the awareness rate was 10.2% (90/883). In addition, among the interns, only 10.2% (90/883) correctly understood the concept of virtual simulation, and most of them (793/883, 89.8%) believed that scenario-simulation training or the use of models for teaching are all the same. Multiple regression analysis showed that the educational level, independent learning ability, and professional identity of the interns were related to use of the application (P<.05). Skills and knowledge that the interns most wanted to acquire included the treatment of hypoglycemia (626/883, 70.9%), functional test simulation (610/883, 69.1%), and blood glucose monitoring technology (485/883, 54.9%). A total of 60.5% (534/883) of the interns wanted to acquire clinical thinking skills, while 16.0% (141/883) wanted to acquire operational skills. Nursing trainees believed that the greatest obstacles to virtual simulation included limited time (280/883, 31.7%), the degree of simulation (129/883, 14.6%), the demand for satisfaction (108/883, 12.2%), and test scores (66/883, 7.5%).

Conclusions: The understanding and usage rate of diabetes virtual simulation teaching applications by Chinese nursing interns is very low. However, they have high requirements regarding this teaching method. Conducting high-quality randomized controlled trials and designing applications that are suitable for the needs of different nurse trainees will increase students' interest in learning and help improve diabetes knowledge among nursing interns.
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http://dx.doi.org/10.2196/29498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461537PMC
September 2021

Relationship Between Smoking and Pressure Injury Risk: A Systematic Review and Meta-Analysis.

Wound Manag Prev 2021 Sep;67(9):34-46

School of Public Health, Nantong University, Nantong, Jiangsu.

Background: Smoking is a risk factor for many diseases.

Purpose: This study explored the relationship between current or past smoking and pressure injury (PI) risk through a systematic review and meta-analysis.

Methods: The databases PubMed, Web of Science, and China National Knowledge Infrastructure were searched for the years between 2001 and 2020. Quality of evidence was estimated by the Newcastle-Ottawa Scale. The random effects model was applied to assess the odds ratios (OR) and 95% confidence intervals (CI); pooled adjusted OR and 95% CI, subgroup analysis, publication bias, sensitivity analyses, and meta-regression analysis were performed.

Results: Fifteen (15) studies (12 retrospective and 3 prospective) comprising data on 11 304 patients were eligible for inclusion in the review. The meta-analysis demonstrated that smoking increased the risk of PI (OR = 1.498; 95% CI, 1.058-2.122), and the pooled adjusted OR (1.969) and 95% CI (1.406-2.757) confirmed this finding. Publication bias was not detected by funnel plot, Begg's test (P = .322), or Egger's test (P = .666). Subgroup analyses yielded the same observations in both retrospective (OR = 1.607; 95% CI, 1.043-2.475) and prospective (OR = 1.218; 95% CI, 0.735-2.017) studies. The results were consistent across sensitivity analyses (OR = 1.07; 95% CI, 1.043- 2.475). Relevant heterogeneity moderators were not identified by meta-regression analysis with PI incidence (P = .466), years of patient data included (P = .637), mean patient age (P = .650), and diabetes mellitus diagnosis (P = .509).

Conclusion: This study found that individuals who are current or formers smokers have an almost 1.5 times higher risk of PI development than do those who do not smoke.
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September 2021

Group 2 innate lymphoid cells in patients with nonasthmatic eosinophilic bronchitis.

Allergy 2021 Aug 29. Epub 2021 Aug 29.

Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

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http://dx.doi.org/10.1111/all.15068DOI Listing
August 2021

The total resection rate of glioma can be improved by the application of US-MRI fusion combined with contrast-enhanced ultrasound.

Clin Neurol Neurosurg 2021 Sep 14;208:106892. Epub 2021 Aug 14.

Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China. Electronic address:

Objective: This study was performed to evaluate the diagnostic performance of ultrasound-magnetic resonance imaging (MRI) fusion combined with contrast-enhanced ultrasound and to explore its role in improving the total tumor resection rate.

Methods: Between January 2018 and December 2018, 16 patients in the observation group and 23 patients in the control group were enrolled in this study. The tumor depth and brain shift distance were analyzed, as well as the peak intensity and microvessel density of different grades of gliomas in the observation group. Finally, we compared the difference in total resection rate between the observation and control groups.

Results: Using ultrasound during operations, we found a significant negative correlation between brain shift distance and tumor depth, with correlation coefficient r=-0.868(P<0.05). In glioma, the peak intensity and microvessel density increased synchronously with glioma grade(r=0.806, P<0.05). The total resection rate of lesions was significantly higher in the observation group than in the control group (P<0.05).

Conclusions: The application of ultrasound-MRI fusion combined with contrast-enhanced ultrasound can improve the total resection rate of lesions, thus playing an important role in clinical practice.
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http://dx.doi.org/10.1016/j.clineuro.2021.106892DOI Listing
September 2021

A Structural Equation Model of Health-Related Quality of Life in Chinese Patients With Rheumatoid Arthritis.

Front Psychiatry 2021 4;12:716996. Epub 2021 Aug 4.

Center for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, China.

The aim of this study was to examine how body image, Disease Activity Score in 28 joints, the feeling of being anxious, depression, fatigue, quality of sleep, and pain influence the quality of life (QoL) in patients with rheumatoid arthritis (RA). A multicenter cross-sectional survey with convenience sampling was conducted from March 2019 and December 2019, 603 patients with RA from five hospitals were evaluated using the Body Image Disturbance Questionnaire, Disease Activity Score in 28 joints, Hospital Anxiety and Depression Scale, Fatigue Severity Scale, Pittsburgh Sleep Quality Index, Short Form 36 Health Survey, and Global Pain Scale. The relationship between quality of life and other variables was evaluated by using the structural equation model (SEM). A total of 580 patients were recruited. SEM fitted the data very well with a root mean square error of approximation (RMSEA) of 0.072. Comparative fit index of 0.966, and Tucker-Lewis index of 0.936. The symptoms and the normalized factor load of six variables showed that the normalized factor load of pain was 0.99. The QoL model was used to fit an SEM to systematically verify and analyze the population disease data, biological factors, and the direct and indirect effects of the symptom group on the QoL, and the interactions between the symptoms. Therefore, the diagnosis, treatment and rehabilitation of RA is a long-term, dynamic, and complex practical process. Patients' personal symptoms, needs, and experiences also vary greatly. Comprehensive assessment of patients' symptoms, needs, and experiences, as well as the role of social support cannot be ignored, which can help to meet patients' nursing needs, improve their mood and pain-based symptom management, and ultimately improve patients' QoL.
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http://dx.doi.org/10.3389/fpsyt.2021.716996DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371236PMC
August 2021

Correction: PLK1/vimentin signaling facilitates immune escape by recruiting Smad2/3 to PD-L1 promoter in metastatic lung adenocarcinoma.

Cell Death Differ 2021 Aug 17. Epub 2021 Aug 17.

Department of Pharmacy, College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do, Korea.

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http://dx.doi.org/10.1038/s41418-021-00842-8DOI Listing
August 2021

Bioaugmentation improves the anaerobic co-digestion of cadmium-containing plant residues and cow manure.

Environ Pollut 2021 Nov 2;289:117885. Epub 2021 Aug 2.

MOE Key Laboratory of Cell Activities and Stress Adaptations, School of Life Sciences, Lanzhou University, Lanzhou, Gansu, 730000, PR China; Key Laboratory for Resources Utilization Technology of Unconventional Water of Gansu Province, Gansu Academy of Membrane Science and Technology, Duanjiatanlu #1272, Lanzhou, 730020, PR China. Electronic address:

Phytoremediation causes a large quantity of phytoremediation residues rich in heavy metals (HMs). This kind of plant residue can be used as a substrate for anaerobic digestion (AD) to reduce the content of HM-containing biomass, but high concentrations of HMs will inhibit the digestion efficiency and reduce the conversion efficiency of plant residues. Bioaugmentation may be an effective method to improve the degradation efficiency and methane yield of plant residues rich in HMs. In this study, a cellulose-degrading anaerobic bacteria Paracoccus sp. Termed strain LZ-G1 was isolated from cow dung, which can degrade cellulose and simultaneously adsorb Cd. The Cd (10 mg/L)-adsorbtion efficiency and cellulose (463.12 g/kg)-degradation rate were 65.1 % and 60.59 %, respectively. In addition, using the strain LZ-G1 bioaugmented Cd-containing plant residues and cow manure mixed AD system, the system's biogas and methane production significantly increased (98.97 % and 142.03 %, respectively). During the AD process, the strain LZ-G1 was successfully colonized in the digestion system. Furthermore, the microbial community analysis revealed that LZ-G1 bioaugmentation alleviates the toxicity of free Cd to the microbial community in the AD system, regulates and restores the archaea genus dominant in the methanogenesis stage, and restores the relative abundance of dominant bacteria associated with biomass hydrolysis. The restoration of the microbial community increased the biogas yield and methane production rate. Thus, bioaugmentation provides an easy and a feasible method for the actual on-site treatment of HM-rich phytoremediation residues.
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http://dx.doi.org/10.1016/j.envpol.2021.117885DOI Listing
November 2021

Gout-associated monosodium urate crystal-induced necrosis is independent of NLRP3 activity but can be suppressed by combined inhibitors for multiple signaling pathways.

Acta Pharmacol Sin 2021 Aug 10. Epub 2021 Aug 10.

Department of Immunobiology, College of Life Science and Technology, Jinan University, Guangzhou, 510632, China.

Monosodium urate (MSU) crystals, the etiological agent of gout, are formed in joints and periarticular tissues due to long-lasting hyperuricemia. Although MSU crystal-triggered NLRP3 inflammasome activation and interleukin 1β (IL-1β) release are known to have key roles in gouty arthritis, recent studies revealed that MSU crystal-induced necrosis also plays a critical role in this process. However, it remains unknown what forms of necrosis have been induced and whether combined cell death inhibitors can block such necrosis. Here, we showed that MSU crystal-induced necrosis in murine macrophages was not dependent on NLRP3 inflammasome activation, as neither genetic deletion nor pharmacological blockade of the NLRP3 pathway inhibited the necrosis. Although many cell death pathways (such as ferroptosis and pyroptosis) inhibitors or reactive oxygen species inhibitors did not have any suppressive effects, necroptosis pathway inhibitors GSK'872 (RIPK3 inhibitor), and GW806742X (MLKL inhibitor) dose-dependently inhibited MSU crystal-induced necrosis. Moreover, a triple combination of GSK'872, GW806742X, and IDN-6556 (pan-caspase inhibitor) displayed enhanced inhibition of the necrosis, which was further fortified by the addition of MCC950 (NLRP3 inhibitor), suggesting that multiple cell death pathways might have been triggered by MSU crystals. Baicalin, a previously identified inhibitor of NLRP3, inhibited MSU crystal-induced inflammasome activation and suppressed the necrosis in macrophages. Besides, baicalin gavage significantly ameliorated MSU crystal-induced peritonitis in mice. Altogether, our data indicate that MSU crystals induce NLRP3-independent necrosis, which can be inhibited by combined inhibitors for multiple signaling pathways, highlighting a new avenue for the treatment of gouty arthritis.
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http://dx.doi.org/10.1038/s41401-021-00749-7DOI Listing
August 2021

A Brighton Collaboration standardized template with key considerations for a benefit/risk assessment for a soluble glycoprotein vaccine to prevent disease caused by Nipah or Hendra viruses.

Vaccine 2021 09 7;39(38):5436-5441. Epub 2021 Aug 7.

Brighton Collaboration, a Program of the Task Force for Global Health, Decatur, GA, USA.

Auro Vaccines LLC has developed a protein vaccine to prevent disease from Nipah and Hendra virus infection that employs a recombinant soluble Hendra glycoprotein (HeV-sG) adjuvanted with aluminum phosphate. This vaccine is currently under clinical evaluation in a Phase 1 study. The Benefit-Risk Assessment of VAccines by TechnolOgy Working Group (BRAVATO; ex-V3SWG) has prepared a standardized template to describe the key considerations for the benefit-risk assessment of protein vaccines. This will help key stakeholders to assess potential safety issues and understand the benefit-risk of such a vaccine platform. The structured and standardized assessment provided by the template may also help contribute to improved public acceptance and communication of licensed protein vaccines.
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http://dx.doi.org/10.1016/j.vaccine.2021.07.030DOI Listing
September 2021

Wetting-regulated gas-involving (photo)electrocatalysis: biomimetics in energy conversion.

Chem Soc Rev 2021 Sep 20;50(18):10674-10699. Epub 2021 Sep 20.

School of Chemical & Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459 Singapore.

(Photo)electrolysis of water or gases with water to species serving as industrial feedstocks and energy carriers, such as hydrogen, ammonia, ethylene, propanol, , has drawn tremendous attention. Moreover, these processes can often be driven by renewable energy under ambient conditions as a sustainable alternative to traditional high-temperature and high-pressure synthesis methods. In addition to the extensive studies on catalyst development, increasing attention has been paid to the regulation of gas transport/diffusion behaviors during gas-involving (photo)electrocatalytic reactions towards the goal of creating industrially viable catalytic systems with high reaction rates, excellent long-term stabilities and near-unity selectivities. Biomimetic surfaces and systems with special wetting capabilities and structural advantages can shed light on the future design of (photo)electrodes and address long-standing challenges. This article is dedicated to bridging the fields of wetting and catalysis by reviewing the cutting-edge design methodologies of both gas-evolving and gas-consuming (photo)electrocatalytic systems. We first introduce the fundamentals of various in-air/underwater wetting states and their corresponding bioinspired structural properties. The relationship amongst the bubble transport behavior, wettability, and porosity/tortuosity is also discussed. Next, the latest implementations of wetting-related design principles for gas-evolving reactions ( the hydrogen evolution reaction and oxygen evolution reaction) and gas-consuming reactions ( the oxygen reduction reaction and CO reduction reaction) are summarized. For photoelectrode designs, additional factors are taken into account, such as light absorption and the separation, transport and recombination of photoinduced electrons and holes. The influences of wettability and 3D structuring of (photo)electrodes on the catalytic activity, stability and selectivity are analyzed to reveal the underlying mechanisms. Finally, remaining questions and related future perspectives are outlined.
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http://dx.doi.org/10.1039/d1cs00258aDOI Listing
September 2021

ADAM17 and NF-κB p65 form a positive feedback loop that facilitates human esophageal squamous cell carcinoma cell viability.

Int J Clin Exp Pathol 2021 15;14(7):845-854. Epub 2021 Jul 15.

Department of Gastroenterology, Affiliated Hospital 2 of Nantong University Nantong 226001, China.

A Disintegrin and metalloproteinase 17 (ADAM17) was proposed to cooperate with NF-κB p65, promoting tumorigenesis and progression of several human cancers. However, the role of ADAM17 remains unknown in human esophageal squamous cell carcinoma (ESCC). In this study, gene expression analyses and cell viability assays suggested that knockdown of ADAM17 suppressed ESCC cell viability. Gene expression analyses and ChIP-qPCR revealed that NF-κB p65 positively regulated ADAM17 expression by binding to the ADAM17 promoter. Rescue experiments showed that overexpression of ADAM17 in NF-κB p65-depleted ESCC cells restored cell viability. In addition, western blot analyses and ChIP-qPCR indicated that ADAM17 was responsible for the persistent activation of NF-κB p65 and contributed to ADAM17 expression in ESCC cells. In conclusion, we propose that ADAM17-activated NF-κB p65 signaling positively regulates ADAM17 expression, and facilitates ESCC cell viability.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339723PMC
July 2021

Circulating IL-17 Level Is Positively Associated with Disease Activity in Patients with Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis.

Biomed Res Int 2021 21;2021:9952463. Epub 2021 Jul 21.

Faculty of Nursing, Chiang Mai University, Chiangmai, Thailand.

Previous studies on the relationship between the circulating level of interleukin-17 (IL-17) and disease activity in systemic lupus erythematosus (SLE) were contradictory. This study is aimed at quantitatively assessing the correlation between the circulating IL-17 level and disease activity in SLE patients. A systematic search for related literature was conducted via PubMed, Web of Science, EMBASE, and Cochrane Library (up to January 26, 2021). The relationship between circulating IL-17 levels and SLE activity was evaluated using Fisher's value, which was then converted to . The standardized mean difference (SMD) and its 95% confidence interval (CI) were used to describe the difference between the circulating IL-17 level in patients with active and inactive SLE. STATA 16.0 was used to perform statistical analysis. Random-effects model was performed to synthesize data. Twenty-six studies involving 1,560 SLE patients were included in this review. The pooled value was 0.38 (95% CI: 0.25-0.50; = 83.8%, < 0.001) between the SLE activity and circulating level of IL-17. Patients with active SLE had higher level of circulating IL-17 than that of inactive (pooled SMD = 0.95, 95% CI: 0.38-1.53; = 90.5%, < 0.001). The subgroup analysis suggested that the region and detection method of circulating IL-17 might not be a source of heterogeneity. No significant publication bias was found. In summary, circulating IL-17 level has a low positive relationship with SLE activity. It is necessary to carefully consider the use of circulating IL-17 as a biomarker of the disease activity in SLE patients. The relationship between the circulating level of IL-17 and SLE activity should be further confirmed in randomized controlled studies.
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http://dx.doi.org/10.1155/2021/9952463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318742PMC
September 2021

Artificial light reduces foraging opportunities in wild least horseshoe bats.

Environ Pollut 2021 Nov 8;288:117765. Epub 2021 Jul 8.

Jilin Provincial Key Laboratory of Animal Resource Conservation and Utilization, Northeast Normal University, 2555 Jingyue Street, Changchun, 130117, China; College of Life Science, Jilin Agricultural University, 2888 Xincheng Street, Changchun, 130118, China. Electronic address:

Artificial light at night has been proposed as a global threat to biodiversity. Insectivorous bats are strictly nocturnal animals that are vulnerable to disruption from artificial light. Given that many light-sensitive bats tend to avoid night light during roost departure, it is often assumed that nighttime light pollution reduces their foraging opportunities, albeit empirical evidence in support of this hypothesis remains elusive. Here, we used least horseshoe bats, Rhinolophus pusillus, to assess whether white artificial light is detrimental for the opportunities of foraging. We manipulated the levels of ambient illumination and perceived predation risk inside the bat roost. We monitored bats' emergence activity using high-speed video and audio recording systems. DNA-based faecal dietary analysis and insect survey were applied to determine activity time of prey in foraging areas. Following experimentally manipulation of white light-emitting diode (LED) lighting 0-15 min after sunset, bat pass, flight duration, and echolocation pulse emission decreased. The mean emergence time of bats flying out was delayed by 14 min under lit treatment compared with the dark control. Only 10% of bats left for foraging during 40 min of light exposure. Aversive effects of LED light on bat emergence were robust regardless of the presence of a potential predator. Insect prey reached a peak of abundance between 30 and 60 min after sunset. These results demonstrate that white artificial light hinders evening emergence behavior in least horseshoe bats, leading to a mismatch between foraging onset and peak food availability. Our findings highlight that light pollution overrides foraging onset, suggesting the importance of improving artificial lighting scheme near the roosts of light-sensitive bats.
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http://dx.doi.org/10.1016/j.envpol.2021.117765DOI Listing
November 2021

Case Report: Predominant Tubulointerstitial Lupus Nephritis or the Combination With IgG4-Related Disease?

Front Med (Lausanne) 2021 28;8:684889. Epub 2021 Jun 28.

Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.

Isolated or dominant tubulointerstitial lupus nephritis is rare. Here, we reported a 67-year-old man diagnosed with systemic lupus erythematosus (SLE) based on clinical and laboratory criteria, who was showing impaired renal function and non-nephrotic range proteinuria in the past 2 years. Renal biopsy showed almost normal glomeruli, but the tubulointerstitium showed "storiform" pattern with interstitial infiltration of IgG3 predominant plasma cells. Immunofluorescence showed linear and granular staining of IgG and C1q along TBM and interstitium. He started on medium dose of oral steroids and mycophenolate mofetil, which were gradually tapered. As a result, his renal function improved over a few days. Now, he continued on low dose steroids and mycophenolate mofetil with no evidence of relapse.
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http://dx.doi.org/10.3389/fmed.2021.684889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273166PMC
June 2021

Effects of water stably-enriched with oxygen as a novel method of tissue oxygenation on mitochondrial function, and as adjuvant therapy for type 2 diabetes in a randomized placebo-controlled trial.

PLoS One 2021 14;16(7):e0254619. Epub 2021 Jul 14.

Department of Medicine, Changi General Hospital, Singapore, Singapore.

Background: Diabetes mellitus is associated with inadequate delivery of oxygen to tissues. Cellular hypoxia is associated with mitochondrial dysfunction which increases oxidative stress and hyperglycaemia. Hyperbaric oxygenation therapy, which was shown to improve insulin sensitivity, is impractical for regular use. We evaluated the effects of water which is stably-enriched with oxygen (ELO water) to increase arterial blood oxygen levels, on mitochondrial function in the presence of normal- or high-glucose environments, and as glucose-lowering therapy in humans.

Methods: We compared arterial blood oxygen levels in Sprague-Dawley rats after 7 days of ad libitum ELO or tap water consumption. Mitochondrial stress testing, and flow cytometry analysis of mitochondrial mass and membrane potential, were performed on human HepG2 cells cultured in four Dulbecco's Modified Eagle Medium media, made with ELO water or regular (control) water, at normal (5.5 mM) or high (25 mM) glucose concentrations. We also randomized 150 adults with type 2 diabetes (mean age 53 years, glycated haemoglobin HbA1c 8.9% [74 mmol/mol], average duration of diabetes 12 years) to drink 1.5 litres daily of bottled ELO water or drinking water.

Results: ELO water raised arterial oxygen tension pO2 significantly (335 ± 26 vs. 188 ± 18 mmHg, p = 0.006) compared with tap water. In cells cultured in control water, mitochondrial mass and membrane potential were both significantly lower at 25 mM glucose compared with 5.5 mM glucose; in contrast, mitochondrial mass and membrane potential did not differ significantly at normal or high glucose concentrations in cells cultured in ELO water. The high-glucose environment induced a greater mitochondrial proton leak in cells cultured in ELO water compared to cells cultured in control medium at similar glucose concentration. In type 2 diabetic adults, HbA1c decreased significantly (p = 0.002) by 0.3 ± 0.7% (4 ± 8 mmol/mol), with ELO water after 12 weeks of treatment but was unchanged with placebo.

Conclusions: ELO water raises arterial blood oxygen levels, appears to have a protective effect on hyperglycaemia-induced reduction in mitochondrial mass and mitochondrial dysfunction, and may be effective adjuvant therapy for type 2 diabetes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254619PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8279347PMC
November 2021
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