Publications by authors named "Lei Cheng"

878 Publications

Methanogenic archaea use a bacteria-like methyltransferase system to demethoxylate aromatic compounds.

ISME J 2021 Jun 18. Epub 2021 Jun 18.

Department of Microbiology, Institute for Water and Wetland Research, Radboud University, Nijmegen, The Netherlands.

Methane-generating archaea drive the final step in anaerobic organic compound mineralization and dictate the carbon flow of Earth's diverse anoxic ecosystems in the absence of inorganic electron acceptors. Although such Archaea were presumed to be restricted to life on simple compounds like hydrogen (H), acetate or methanol, an archaeon, Methermicoccus shengliensis, was recently found to convert methoxylated aromatic compounds to methane. Methoxylated aromatic compounds are important components of lignin and coal, and are present in most subsurface sediments. Despite the novelty of such a methoxydotrophic archaeon its metabolism has not yet been explored. In this study, transcriptomics and proteomics reveal that under methoxydotrophic growth M. shengliensis expresses an O-demethylation/methyltransferase system related to the one used by acetogenic bacteria. Enzymatic assays provide evidence for a two step-mechanisms in which the methyl-group from the methoxy compound is (1) transferred on cobalamin and (2) further transferred on the C-carrier tetrahydromethanopterin, a mechanism distinct from conventional methanogenic methyl-transfer systems which use coenzyme M as final acceptor. We further hypothesize that this likely leads to an atypical use of the methanogenesis pathway that derives cellular energy from methyl transfer (Mtr) rather than electron transfer (FH re-oxidation) as found for methylotrophic methanogenesis.
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http://dx.doi.org/10.1038/s41396-021-01025-6DOI Listing
June 2021

Modulation of the lifespan of by the controlled release of nitric oxide.

Chem Sci 2020 Jul 29;11(33):8785-8792. Epub 2020 Jul 29.

Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering Shanghai China

The frontier of nitric oxide biology has gradually shifted from mechanism elucidation to biomanipulation, cell-proliferation promotion, cell-apoptosis induction, and lifespan modulation. This warrants biocompatible nitric oxide (NO) donating materials, whose NO release is not only controlled by a bioorthogonal trigger, but also self-calibrated allowing real-time monitoring and hence an onset/offset of the NO release. Additionally, the dose of NO release should be facilely adjusted in a large dynamic range; flux and the dose are critical to the biological outcome of NO treatment. self-assembly of a PEGylated small-molecule NO donor, we developed novel NO-donating nanoparticles (PEG-NORM), which meet all the aforementioned criteria. We showcased that a low flux of NO induced cell proliferation, while a high flux induced cell oxidative stress and, ultimately, death. Notably, PEG-NORM was capable of efficiently modulating the lifespan of . The average lifespan of could be fine-tuned to be as short as 15.87 ± 0.29 days with a high dose of NO, or as long as 21.13 ± 0.41 days with a low dose of NO, compared to an average life-span of 18.87 ± 0.46 days. Thus, PEG-NORM has broad potential in cell manipulation and life-span modulation and could drive the advancement of NO biology and medicine.
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http://dx.doi.org/10.1039/c9sc06072cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163451PMC
July 2020

Variation of Metagenome From Feedstock to Digestate in Full-Scale Biogas Plants.

Front Microbiol 2021 28;12:660225. Epub 2021 May 28.

Guangdong Laboratory for Lingnan Modern Agriculture (Shenzhen Branch), Genome Analysis Laboratory of the Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.

Anaerobic digestion (AD) has been widely used to resolve the problem of organic wastes worldwide. Previous studies showed that the types of feedstock have a great influence on the AD microbiome, and a huge number of AD populations are migrated from upstream feedstocks. However, the changes of microbial compositions from feedstock to AD digestate are still less understood. We collected feedstock samples from 56 full-scale biogas plants, generated 1,716 Gb feedstock metagenomic data in total, and constructed the first comprehensive microbial gene catalog of feedstock containing 25.2 million genes. Our result indicated that the predominant phyla in feedstock are , , and , which is similar to that in AD digestate, and the microbial diversity of feedstock samples is higher than that of AD digestate samples. In addition, the relative abundance of most genes involved in methanogenesis increase from feedstock to AD digestate. Besides, the amount of antibiotic resistance genes (ARGs) and pathogenic bacteria in AD are effectively reduced compared to feedstocks. This study provides a comprehensive microbial gene catalog of feedstock, and deepens the understanding of variation of microbial communities from feedstock to AD digestate of full-scale AD. The results also suggest the potential of AD to reduce the level of ARGs and pathogens in animal manure.
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http://dx.doi.org/10.3389/fmicb.2021.660225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193575PMC
May 2021

Novel dental implant modifications with two-staged double benefits for preventing infection and promoting osseointegration and .

Bioact Mater 2021 Dec 15;6(12):4568-4579. Epub 2021 May 15.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, China.

Peri-implantitis are a major problem causing implant failure these days. Accordingly, anti-infection during the early stage and subsequent promotion of osseointegration are two main key factors to solve this issue. Micro-arc oxidation (MAO) treatment is a way to form an oxidation film on the surface of metallic materials. The method shows good osteogenic properties but weak antibacterial effect. Therefore, we developed combined strategies to combat severe peri-implantitis, which included the use of a novel compound, PD, comprising dendrimers poly(amidoamine) (PAMAM) loading dimethylaminododecyl methacrylate (DMADDM) as well as MAO treatment. Here, we explored the chemical properties of the novel compound PD, and proved that this compound was successfully synthesized, with the loading efficiency and encapsulation efficiency of 23.91% and 31.42%, respectively. We further report the two-stage double benefits capability of PD + MAO: (1) in the first stage, PD + MAO could decrease the adherence and development of biofilms by releasing DMADDM in the highly infected first stage after implant surgery both and ; (2) in the second stage, PD + MAO indicated mighty anti-infection and osteoconductive characteristics in a rat model of peri-implantitis . This study first reports the two-staged, double benefits of PD + MAO, and demonstrates its potential in clinical applications for inhibiting peri-implantitis, especially in patients with severe infection risk.
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http://dx.doi.org/10.1016/j.bioactmat.2021.04.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141509PMC
December 2021

Corrigendum: Reactive Oxygen Species in Pathogen Clearance: The Killing Mechanisms, the Adaption Response, and the Side Effects.

Front Microbiol 2021 13;12:685133. Epub 2021 May 13.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

[This corrects the article DOI: 10.3389/fmicb.2020.622534.].
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http://dx.doi.org/10.3389/fmicb.2021.685133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8152934PMC
May 2021

Translation and validation of TRANSITION-Q for Chinese pediatric cancer survivors.

J Pediatr Nurs 2021 May 24;61:130-135. Epub 2021 May 24.

School of Nursing, Fudan University, Shanghai 200032, China. Electronic address:

Purpose: Cancer survivorship starts at diagnosis. Transition readiness is an important indicator for pediatric cancer survivors to move from pediatric to adult medical care. Appropriate measurement of transition readiness can facilitate better cancer survivorship. This study aimed to translate and validate of the English version of the TRANSITION-Q into Chinese.

Design And Methods: The translation followed the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) best-practice guidelines for the translation and cultural adaptation of patient-reported outcome measures (PROM). A cross- psychometric testing on reliability and validity were conducted from a convenient sample of Chinese adolescent cancer survivors aged 10-19 years.

Results: Two hundred seventy-one pediatric cancer patients were recruited for the psychometric validation. The 14-item Chinese TRANSITION-Q demonstrated adequate reliability. In exploratory factorial analyses and confirmatory factor analysis, a two-factor structure emerged with a variance of 54.78%, demonstrating construct validity. Convergent validity test showed TRANSITION-Q score was significantly positively correlated with self-efficacy (r = -0.84, p = 0.002). The known-group validity demonstrated the older group (age ≥14 years) had a significantly higher mean TRANSITION-Q score than the younger group (age < 14 years) (p = 0.04).

Conclusion: The Chinese version of the TRANSITION-Q is reliable and valid and can be used in Chinese research and clinical settings.

Implications For Practice: This scale can be used in Chinese clinical and research settings to investigate understanding of transition readiness in Chinese pediatric cancer survivors.
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http://dx.doi.org/10.1016/j.pedn.2021.05.009DOI Listing
May 2021

Pain Reported by Chinese Children During Cancer Treatment: Prevalence, Intensity, Interference, and Management.

Cancer Nurs 2021 May 19. Epub 2021 May 19.

Author Affiliations: School of Nursing, Fudan University, Shanghai, China (Drs Cheng and Yuan); Shanghai University of Medicine & Health Sciences, Shanghai, China (Ms Wang); and The Hospital for Sick Children, Lawrence S. Bloomberg, Faculty of Nursing, University of Toronto, Toronto, Canada (Dr Stinson).

Background: Pain is a frequently reported and distressing symptoms during cancer treatment. However, there is limited evidence on pain reported by Chinese children with cancer.

Objectives: This study aimed to investigate the prevalence, intensity, interference, and management of pain reported by Chinese children during cancer treatment and explore the predictors of pain interference.

Methods: We conducted a cross-sectional survey to investigate the pain intensity, pain interference, co-occurring symptoms (anger, anxiety, depression, fatigue), and pain management strategies reported by children 8 years and older undergoing active cancer treatment in 4 Chinese hospitals.

Results: Data were analyzed for 187 children. The prevalence of moderate to severe pain (≥4/10) was 38.50%, with an average pain interference score of 52.97 out of 100. Approximately 24% of children were prescribed pain medicine. Pain interference and pain intensity were marginally correlated (r = 0.047, P < .01) and were both positively correlated with pain duration and co-occurring symptoms and negatively correlated with perceived pain alleviation (all P < .01). Multiple regression analyses suggested that severe pain intensity (B = 2.028, P = .003) and fatigue (B = 0.440, P < .001) significantly predicted higher levels of pain interference (R2 = 0.547, F = 23.102, P < .001).

Conclusion: Chinese children with cancer reported a low pain intensity score but a relatively high level of pain interference. According to the children's reports, pain has not been sufficiently addressed through Chinese pediatric oncology supportive care.

Implications For Practice: There is an urgent requirement for comprehensive pain assessment and standardized, targeted interventions in Chinese pediatric oncology pain management.
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http://dx.doi.org/10.1097/NCC.0000000000000958DOI Listing
May 2021

Synonymous point mutation of gtfB gene caused by therapeutic X-rays exposure reduced the biofilm formation and cariogenic abilities of Streptococcus mutans.

Cell Biosci 2021 May 17;11(1):91. Epub 2021 May 17.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, 610041, China.

Background: The shift of oral microbiota is a critical factor of radiation caries in head and neck cancer patients after the radiotherapy. However, the direct effects of irradiation on the genome and virulence of cariogenic bacteria are poorly described. Here we investigated the genomic mutations and virulence change of Streptococcus mutans (S. mutans), the major cariogenic bacteria, exposed to the therapeutic doses of X-rays.

Results: X-ray reduced the survival fraction of S. mutans and impacted its biofilm formation. We isolated a biofilm formation-deficient mutant #858 whose genome only possessed three synonymous mutations (c.2043 T > C, c.2100C > T, c.2109A > G) in gtfB gene. The "silent mutation" of c.2043 T > C in gtfB gene can cause the down-regulation of all of the gtfs genes' expression and decrease the GtfB enzyme secretion without the effect on the growth due to the codon bias. #858 and synonymous point mutation strain gtfB , similar to the gtfB gene null mutant Δ gtfB, can significantly decrease the extracellular polysaccharide production, biofilm formation and cariogenic capabilities both in vitro and in vivo compared with wild type.

Conclusion: The direct exposure of X-ray radiation can affect the genome and virulence of oral bacteria even at therapeutic doses. The synonymous mutations of genome are negligent factors for gene expression and related protein translation due to the codon usage frequency.
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http://dx.doi.org/10.1186/s13578-021-00608-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130306PMC
May 2021

The effect of local intraoperative corticosteroid application on postoperative dysphagia following anterior cervical spine surgery.

Neurosurg Rev 2021 May 12. Epub 2021 May 12.

Department of Neurosurgery, Xuanwu Hospital, China International Neuroscience Institute, Capital Medical University, 45 Changchun Street, Beijing, 100053, China.

Dysphagia is a common complication following anterior cervical spine surgery (ACSS). Although several literatures have reported the potential benefit of local corticosteroid application on dysphagia, its safety and efficacy are still unclear. A systematic review was performed aiming to evaluate the evidence of local corticosteroid application in prevention or treatment of postoperative dysphagia following ACSS. A systematic search was performed in September 2018 in PubMed and Embase database. The following information was extracted: study investigator, year of publication, number of patients, study design, inclusion/exclusion criteria, administration protocol of steroid, type of surgical procedure, number of levels performed, assessment methodology of dysphagia, radiologic assessment of prevertebral soft tissue swelling (PSTS), follow-up time points, outcome of dysphagia, and corticosteroid-related complications. Qualitative synthesis was performed. Finally, 5 studies met the inclusion/exclusion criteria. Four studies found that local corticosteroid application could decrease the incidence and magnitude of postoperative dysphagia while 1 study showed no effect on dysphagia significantly at 6 weeks and 3 months follow-up time. A total of 2325 patients received local corticosteroid intraoperatively; no early corticosteroid-related complication was reported. Totally, 4 adverse events occurred in long-term follow-up time, including 2 bone nonunion at 1.5 and 2.5 years postoperatively, 2 esophageal perforation at 2 months and 11 months of follow-up, respectively. Local corticosteroid application can reduce the incidence and severity of dysphagia following ACSS without increasing early corticosteroid-related complications. But further high-quality study is necessary to analyze potential delayed complications.
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http://dx.doi.org/10.1007/s10143-019-01207-zDOI Listing
May 2021

Screening and identification of microRNAs from plasma-derived extracellular vesicles (EVs) of Dazu black goat (Capra hircus) in early pregnant stages.

Gene 2021 Jul 9;790:145706. Epub 2021 May 9.

College of Animal Science and Technology, Southwest University, Chongqing Key Laboratory of Herbivore Science, Chongqing Engineering Research Center for Herbivores Resource Protection and Utilization, Chongqing 400715, PR China. Electronic address:

Previous studies have shown that extracellular vesicles (EVs) containing proteins, lipids, nucleic acids and other biological components exist in all kinds of body fluids. EVs, as an intercellular communication carrier, regulate the functions of its target cells by transporting biomacromolecules between cells. In this study, a total of six female Dazu black goats were divided into NP group (NP, non-pregnant group) and P30 (P30, 30-day pregnant group). The goats in NP group (n = 3) were in estrus, but failed to fertilize; the other goats in P30 group (n = 3) were fertilized by natural mating. Firstly, goats plasma-derived EVs were isolated using ultracentrifugation. Secondly, EVs were identified by transmission electron microscope (TEM), dynamic light scattering (DLS), and by testing its markers (CD9 and CD63) using west blotting in NP and P30 groups, respectively. Thirdly, EVs related miRNAs were sequenced and analyzed by bioinformatics method. Data shows that miR-31-5p, miR-137-3p, novel_miR_1355, novel_miR_734 and novel_miR_736 exclusively were expressed in P30 group. Their target genes were significantly enriched in the axon guidance, the Notch signaling pathway, the Wnt signaling pathway, tight junction and the Hippo signaling pathway. And miRNA-mRNA interactive network analysis reveals potential regulatory functions of miRNAs for goat during early pregnancy. These findings provided theretical references for studying the regulation of plasma-derived EVs between the fetal and placental development, and these candidate miRNAs identified might be as markers for diagnosis of goat early pregnancy.
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http://dx.doi.org/10.1016/j.gene.2021.145706DOI Listing
July 2021

Microbial cancer therapeutics: A promising approach.

Semin Cancer Biol 2021 May 9. Epub 2021 May 9.

Centre for Safe and Improved Food, Scotland's Rural College (SRUC), Kings Buildings, West Mains Road, Edinburgh, EH9 3JG, UK; Biorefining and Advanced Materials Research Center, Scotland's Rural College (SRUC), Kings Buildings, West Mains Road, Edinburgh, EH9 3JG, UK. Electronic address:

The success of conventional cancer therapeutics is hindered by associated dreadful side-effects of antibiotic resistance and the dearth of antitumor drugs' selectivity and specificity. Hence, the conceptual evolution of anti-cancerous therapeutic agents that selectively target cancer cells without impacting the healthy cells or tissues, has led to a new wave of scientific interest in microbial-derived bioactive molecules. Such strategic solutions may pave the way to surmount the shortcomings of conventional therapies and raise the potential and hope for the cure of wide range of cancer in a selective manner. This review aims to provide a comprehensive summary of anti-carcinogenic properties and underlying mechanisms of bioactive molecules of microbial origin, and discuss the current challenges and effective therapeutic application of combinatorial strategies to attain minimal systemic side-effects.
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http://dx.doi.org/10.1016/j.semcancer.2021.05.003DOI Listing
May 2021

Activity and structure of methanogenic microbial communities in sediments of cascade hydropower reservoirs, Southwest China.

Sci Total Environ 2021 Sep 4;786:147515. Epub 2021 May 4.

State Key Laboratory of Environmental Geochemistry, Institute of Geochemistry, Chinese Academy of Sciences, Guiyang 550081, China. Electronic address:

Freshwater reservoirs are an important source of the greenhouse gas methane (CH). However, little is known about the activity and structure of microbial communities involved in methanogenic decomposition of sediment organic matter (SOM) in cascade hydropower reservoirs. In this study, we targeted on sediments of three cascade reservoirs in Wujiang River, Southwest China. Our results showed that the content of sediment organic carbon (SOC) was between 3% and 11%, and it's positively correlated with both C/N ratio and recalcitrant organic carbon content of SOM. Meanwhile, SOC content was positively correlated with CH production rates but had no significant correlation with total CO production rates of the sediments, when rates were normalized to sediment volume. Resultantly, the sediment anaerobic decomposition rates hardly significantly increase along with the SOC content. These results suggested that the terrestrial organic matter accumulated after damming stimulated CH production from the reservoir sediments even though its decomposition rate was limited. Meantime, high throughput sequencing of 16S rRNA genes indicated that not only the hydrogenotrophic and acetoclastic, but also the methylotrophic methanogens (Methanomassiliicoccus) are abundant in the reservoir sediments. Moreover, metagenomic sequencing also suggested that methylotrophic methanogenesis are potentially important in the sediment of cascade reservoirs. Finally, the hydraulic residence time of the reservoir could be the key controlling factor of the structures of bacterial and archaeal communities as well as the CH production rates of the reservoir sediments.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147515DOI Listing
September 2021

The cross-kingdom interaction between Helicobacter pylori and Candida albicans.

PLoS Pathog 2021 May 6;17(5):e1009515. Epub 2021 May 6.

State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China.

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http://dx.doi.org/10.1371/journal.ppat.1009515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101746PMC
May 2021

Insight into the function and evolution of the Wood-Ljungdahl pathway in Actinobacteria.

ISME J 2021 May 5. Epub 2021 May 5.

State Key Laboratory of Biocontrol, Guangdong Provincial Key Laboratory of Plant Resources and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), School of Life Sciences, Sun Yat-Sen University, Guangzhou, PR China.

Carbon fixation by chemoautotrophic microbes such as homoacetogens had a major impact on the transition from the inorganic to the organic world. Recent reports have shown the presence of genes for key enzymes associated with the Wood-Ljungdahl pathway (WLP) in the phylum Actinobacteria, which adds to the diversity of potential autotrophs. Here, we compiled 42 actinobacterial metagenome-assembled genomes (MAGs) from new and existing metagenomic datasets and propose three novel classes, Ca. Aquicultoria, Ca. Geothermincolia and Ca. Humimicrobiia. Most members of these classes contain genes coding for acetogenesis through the WLP, as well as a variety of hydrogenases (NiFe groups 1a and 3b-3d; FeFe group C; NiFe group 4-related hydrogenases). We show that the three classes acquired the hydrogenases independently, yet the carbon monoxide dehydrogenase/acetyl-CoA synthase complex (CODH/ACS) was apparently present in their last common ancestor and was inherited vertically. Furthermore, the Actinobacteria likely donated genes for CODH/ACS to multiple lineages within Nitrospirae, Deltaproteobacteria (Desulfobacterota), and Thermodesulfobacteria through multiple horizontal gene transfer events. Finally, we show the apparent growth of Ca. Geothermincolia and H-dependent acetate production in hot spring enrichment cultures with or without the methanogenesis inhibitor 2-bromoethanesulfonate, which is consistent with the proposed homoacetogenic metabolism.
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http://dx.doi.org/10.1038/s41396-021-00935-9DOI Listing
May 2021

Activation of the kidney sodium chloride cotransporter by the β2-adrenergic receptor agonist salbutamol increases blood pressure.

Kidney Int 2021 Apr 30. Epub 2021 Apr 30.

Department of Biomedicine, Aarhus University, Aarhus DK-8000, Denmark. Electronic address:

The thiazide-sensitive sodium-chloride-cotransporter (NCC) in the kidney distal convoluted tubule (DCT) plays an essential role in sodium and potassium homeostasis. Here, we demonstrate that NCC activity is increased by the β2-adrenoceptor agonist salbutamol, a drug prevalently used to treat asthma. Relative to β1-adrenergic receptors, the β2-adrenergic receptors were greatly enriched in mouse DCT cells. In mice, administration of salbutamol increased NCC phosphorylation (indicating increased activity) within 30 minutes but also caused hypokalemia, which also increases NCC phosphorylation. In ex vivo kidney slices and isolated tubules, salbutamol increased NCC phosphorylation in the pharmacologically relevant range of 0.01-10 μM, an effect observed after 15 minutes and maintained at 60 minutes. Inhibition of the inwardly rectifying potassium channel (Kir) 4.1 or the downstream with-no-lysine kinases (WNKs) and STE20/SPS1-related proline alanine-rich kinase (SPAK) pathway greatly attenuated, but did not prevent, salbutamol-induced NCC phosphorylation. Salbutamol increased cAMP in tubules, kidney slices and mpkDCT cells (model of DCT). Phosphoproteomics indicated that protein phosphatase 1 (PP1) was a key upstream regulator of salbutamol effects. A role for PP1 and the PP1 inhibitor 1 (I1) was confirmed in tubules using inhibitors of PP1 or kidney slices from I1 knockout mice. On normal and high salt diets, salbutamol infusion increased systolic blood pressure, but this increase was normalized by thiazide suggesting a role for NCC. Thus, β2-adrenergic receptor signaling modulates NCC activity via I1/PP1 and WNK-dependent pathways, and chronic salbutamol administration may be a risk factor for hypertension.
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http://dx.doi.org/10.1016/j.kint.2021.04.021DOI Listing
April 2021

Follistatin-Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice through Interacting with TNF- and Smad Signaling Pathway.

Oxid Med Cell Longev 2021 10;2021:6640751. Epub 2021 Apr 10.

Department of Orthopedic, Qilu Hospital, Cheeloo College of Medicine of Shandong University, Jinan, China.

Background: Inflammation plays an important role in intervertebral disc degeneration (IDD). The protein follistatin-like 1 (FSTL1) plays a proinflammatory role in a variety of inflammatory diseases.

Objectives: The purpose of this study was to investigate whether IDD could be delayed by inhibiting FSTL-1 expression.

Methods: We established a puncture-induced IDD model in wild-type and FSTL-1+/- mice and collected intervertebral discs (IVDs) from the mice. Safranin O staining was used to detect cartilage loss of IVD tissue, and HE staining was used to detect morphological changes of IVD tissue. We measured the expression of FSTL-1 and related inflammatory indicators in IVD tissues by immunohistochemical staining, real-time PCR, and Western blotting.

Results: In the age-induced model of IDD, the level of FSTL-1 increased with the exacerbation of degeneration. In the puncture-induced IDD model, FSTL-1-knockdown mice showed a reduced degree of degeneration compared with that of wild-type mice. Further experiments showed that FSTL-1 knockdown also significantly reduced the level of related inflammatory factors in IVD. In vitro experiments showed that FSTL-1 knockdown significantly reduced TNF--induced inflammation. Specifically, the expression levels of the inflammatory factors COX-2, iNOS, MMP-13, and ADAMTS-5 were reduced. Knockdown of FSTL-1 attenuated inflammation by inhibiting the expression of P-Smad1/5/8, P-Erk1/2, and P-P65.

Conclusion: Knockdown of FSTL-1 attenuated inflammation by inhibiting the TNF- response and Smad pathway activity and ultimately delayed IDD.
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http://dx.doi.org/10.1155/2021/6640751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055391PMC
May 2021

Morphological Indicator for Directed Evolution of with a High Heavy Metal Removal Efficiency.

Environ Sci Technol 2021 Jun 29;55(12):7880-7889. Epub 2021 Apr 29.

Department of Chemistry, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.

In the past few decades, microalgae-based bioremediation methods for treating heavy metal (HM)-polluted wastewater have attracted much attention by virtue of their environment friendliness, cost efficiency, and sustainability. However, their HM removal efficiency is far from practical use. Directed evolution is expected to be effective for developing microalgae with a much higher HM removal efficiency, but there is no non-invasive or label-free indicator to identify them. Here, we present an intelligent cellular morphological indicator for identifying the HM removal efficiency of in a non-invasive and label-free manner. Specifically, we show a strong monotonic correlation (Spearman's ρ = -0.82, = 2.1 × 10) between a morphological meta-feature recognized via our machine learning algorithms and the Cu removal efficiency of 19 clones. Our findings firmly suggest that the morphology of cells can serve as an effective HM removal efficiency indicator and hence have great potential, when combined with a high-throughput image-activated cell sorter, for directed-evolution-based development of with an extremely high HM removal efficiency for practical wastewater treatment worldwide.
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http://dx.doi.org/10.1021/acs.est.0c05278DOI Listing
June 2021

The virulence factor GroEL directs the osteogenic and adipogenic differentiation of human periodontal ligament stem cells through the involvement of JNK/MAPK and NF-κB signaling.

J Periodontol 2021 Apr 29. Epub 2021 Apr 29.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Objective: GroEL, a bacterial metabolite, is an important stimulator of inflammation. The aim of this study is to confirm the effect of the virulence factor GroEL on differentiation potential of periodontal ligament (PDL) stem cells (PDLSCs) and the potential mechanisms.

Methods: PDLSCs were obtained from extracted human premolars. GroEL was administered to osteogenic- and adipogenic-induced hPDLSCs. Alkaline phosphatase (ALP) staining, Alizarin Red staining and Oil Red staining were performed. Gene and protein expression were separately measured by qPCR and Western blotting. The expression and localization of activated signaling factors were confirmed by immunofluorescence staining. The inhibitors of myeloid differentiation factor 88 (MyD88, an adaptor protein of TLRs), JNK/MAPK and NF-κB signaling were used to verify their specific effects.

Results: First, we found that GroEL inhibited the osteogenic differentiation and enhanced the adipogenic differentiation of hPDLSCs. Next, we found that GroEL increased the expression of TLR2 and TLR4 and GroEL activated JNK/MAPK and NF-κB signaling, which can be blocked by inhibition of MyD88. Finally, we found that inhibition of MyD88 restored GroEL-induced osteogenic and adipogenic differentiation and blocking JNK/MAPK or NF-κB signaling partly restored GroEL effects.

Conclusion: In the current study, we revealed a potential interaction between bacteria and host cells by showing that GroEL directs the osteogenic and adipogenic differentiation of hPDLSCs by the involvement of JNK/MAPK and NF-κB signaling. This study provides evidence that bacterial products can influence the differentiation of stem cells and reveals potential effect of GroEL on the context of tissue regeneration.
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http://dx.doi.org/10.1002/JPER.20-0869DOI Listing
April 2021

Expanded diversity of Asgard archaea and their relationships with eukaryotes.

Nature 2021 May 28;593(7860):553-557. Epub 2021 Apr 28.

Shenzhen Key Laboratory of Marine Microbiome Engineering, Institute for Advanced Study, Shenzhen University, Shenzhen, P. R. China.

Asgard is a recently discovered superphylum of archaea that appears to include the closest archaeal relatives of eukaryotes. Debate continues as to whether the archaeal ancestor of eukaryotes belongs within the Asgard superphylum or whether this ancestor is a sister group to all other archaea (that is, a two-domain versus a three-domain tree of life). Here we present a comparative analysis of 162 complete or nearly complete genomes of Asgard archaea, including 75 metagenome-assembled genomes that-to our knowledge-have not previously been reported. Our results substantially expand the phylogenetic diversity of Asgard and lead us to propose six additional phyla that include a deep branch that we have provisionally named Wukongarchaeota. Our phylogenomic analysis does not resolve unequivocally the evolutionary relationship between eukaryotes and Asgard archaea, but instead-depending on the choice of species and conserved genes used to build the phylogeny-supports either the origin of eukaryotes from within Asgard (as a sister group to the expanded Heimdallarchaeota-Wukongarchaeota branch) or a deeper branch for the eukaryote ancestor within archaea. Our comprehensive protein domain analysis using the 162 Asgard genomes results in a major expansion of the set of eukaryotic signature proteins. The Asgard eukaryotic signature proteins show variable phyletic distributions and domain architectures, which is suggestive of dynamic evolution through horizontal gene transfer, gene loss, gene duplication and domain shuffling. The phylogenomics of the Asgard archaea points to the accumulation of the components of the mobile archaeal 'eukaryome' in the archaeal ancestor of eukaryotes (within or outside Asgard) through extensive horizontal gene transfer.
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http://dx.doi.org/10.1038/s41586-021-03494-3DOI Listing
May 2021

The noncovalent conjugations of human serum albumin (HSA) with MS/AK and the effect on anti-oxidant capacity as well as anti-glycation activity of Monascus yellow pigments.

Food Funct 2021 Apr 1;12(8):3692-3704. Epub 2021 Apr 1.

State Key Laboratory of Food Nutrition and Safety, College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, PR China.

Monascin (MS) and ankaflavin (AK), as typical yellow lipid-soluble pigments identified from Monascus-fermented products, have been confirmed to possess diverse biological activities such as anti-oxidation, reversing diabetes, and anti-atherosclerosis, and have received increasing attention in recent years. Certainly Monascus-fermented product with a high content of MS/AK is also a concern. The current work explored interactions between MS/AK and human serum albumin (HSA) as well as their influence on the anti-oxidant properties of MS/AK. Moreover, the anti-glycation potential of Monascus-fermented products rich in MS and AK (denoted as Mps) was assessed. The results showed that the fluorescence emission of HSA was quenched by MS/AK through a static quenching mechanism, and MS-HSA and AK-HSA complexes were mainly formed by van der Waals forces and hydrophobic interactions, but AK showed a higher binding affinity than MS. Although the DPPH radical-scavenging abilities of MS-HSA and AK-HSA complexes declined, Mps significantly reduced the formation of fructosamine, α-dicarbonyl compounds and advanced glycation end products (AGEs) in the in vitro glycation model (HSA-glucose). Notably, approximately 80% of fluorescent-AGEs were suppressed by Mps at a concentration of 0.95 mg mL, while aminoguanidine (AG, a reference standard) caused only 65% decrease at the same concentration. Although radical scavenging and metal chelating activities could justify the observed anti-glycation activity of Mps, in-depth research on the structures of other functional compounds present in Mps except MS/AK and reaction mechanisms should be performed. Overall, the present study proved that Mps would be promising sources of food-based anti-glycation agents because of their superior inhibitory effect on AGEs.
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http://dx.doi.org/10.1039/d0fo03025bDOI Listing
April 2021

Differential roles of two isoforms of dopamine D2 receptors in l-dopa-induced abnormal involuntary movements in mice.

Neuroreport 2021 May;32(7):555-561

Department of Pharmaceutical Sciences, Ben and Maytee Fisch College of Pharmacy, The University of Texas at Tyler, Tyler, Texas, USA.

l-dopa and dopamine D2 receptor (D2R) agonists are commonly used to relieve the motor deficits of Parkinson's disease. However, long-term treatment with l-dopa or D2R agonists can induce adverse effects such as abnormal involuntary movements (AIMs), which are major limiting factors in achieving long-term control of parkinsonian syndromes. The pathophysiological mechanisms involved in the development of dopaminergic agonist-induced adverse effects are not well understood. Here, we examined the role of two D2R isoforms, D2S and D2L, in l-dopa-induced AIMs using dopamine D2L knockout (D2L KO) mice (expressing purely D2S) and wild-type mice (expressing predominantly D2L). We found that D2L KO mice displayed markedly enhanced AIMs in response to chronic treatment of l-dopa compared to wild-type mice. The l-dopa-induced enhancement of AIMs in D2L KO mice was significantly reduced by the D2R antagonist eticlopride. D2L KO mice also displayed markedly enhanced AIMs in response to chronic treatment with quinpirole, a preferential D2R agonist. These results suggest that D2S contributes more than D2L to dopaminergic agonist-induced AIMs. Our findings may uncover a new factor that contributes to the pathophysiology of dopaminergic drug-induced AIMs, a characteristic manifestation of dyskinesia and also present in psychosis. There is a possibility that the increased ratio of D2S to D2L in the brain plays a significant role in the development of AIM side effects induced by l-dopa or D2R agonists. See Video Abstract, http://links.lww.com/WNR/A622.
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http://dx.doi.org/10.1097/WNR.0000000000001623DOI Listing
May 2021

Correction to: A novel classification and its clinical significance in Chiari I malformation with syringomyelia based on high‑resolution MRI.

Eur Spine J 2021 Apr 10. Epub 2021 Apr 10.

Department of Neurosurgery, Division of Spine, China, International Neurological Institute, Xuanwu Hospital, Capital Medical University, 45 Changchun Street, Beijing, 100053, People's Republic of China.

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http://dx.doi.org/10.1007/s00586-021-06787-3DOI Listing
April 2021

Resilience analysis of the nexus across water supply, power generation and environmental systems from a stochastic perspective.

J Environ Manage 2021 Jul 3;289:112513. Epub 2021 Apr 3.

State Key Laboratory of Water Resources and Hydropower Engineering Science, Wuhan University, Wuhan, 430072, China; Research Institute for Water Security (RIWS), Wuhan University, Wuhan, 430072, People's Republic of China; Hubei Provincial Key Lab of Water System Science for Sponge City Construction, Wuhan University, Wuhan, 430072, China.

Effects of external disturbances such as the population change on dynamics of water supply, power generation and environmental (WPE) systems have seldom been investigated. Following the WPE nexus profiled in the study of Feng et al. (2016), this study incorporated stochasticity of population, water supply and power generation into the modeling of the dynamical system in the Hehuang region of China, and further quantified resilience measures to understand the system's ability to withstand stochastic disturbances. First, the stochastic differential equations were used to improve the simulation of stochasticity in the WPE nexus. Next, the transient probability distribution functions (pdfs) of system variables, obtained by Monte Carlo simulation, were used to describe the evolutionary process of the system. Finally, the stationary pdfs of variables which reflect stable states of the system were derived to calculate four resilience measures. It is shown that: (1) The system approached a stable state after Year 2400 by calculating the L2 norm of the difference between transient and stationary pdfs. (2) The environmental system was identified as the most vulnerable subsystem because of its long convergence time. (3) The water supply system did not change greatly and it would remain stable at its current low level, i.e., water consumption per capita would be less than 80m. The method adopted in this study is conducive to avoiding risk and the results provide valuable insights for regional management of a WPE nexus.
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http://dx.doi.org/10.1016/j.jenvman.2021.112513DOI Listing
July 2021

Dental Restorative Materials for Elderly Populations.

Polymers (Basel) 2021 Mar 8;13(5). Epub 2021 Mar 8.

State Key Laboratory of Oral Diseases, West China School of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu 610064, China.

The incidence of dental caries, especially root caries, has risen in elderly populations in recent years. Specialized restorative materials are needed due to the specific site of root caries and the age-related changes in general and oral health in the elderly. Unfortunately, the restorative materials commonly used clinically cannot fully meet the requirements in this population. Specifically, the antibacterial, adhesive, remineralization, mechanical, and anti-aging properties of the materials need to be significantly improved for dental caries in the elderly. This review mainly discusses the strengths and weaknesses of currently available materials, including amalgam, glass ionomer cement, and light-cured composite resin, for root caries. It also reviews the studies on novel anti-caries materials divided into three groups, antimicrobial, remineralization, and self-healing materials, and explores their potential in the clinical use for caries in the elderly. Therefore, specific restorative materials for caries in the elderly, especially for root caries, need to be further developed and applied in clinical practice.
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http://dx.doi.org/10.3390/polym13050828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7962827PMC
March 2021

An in vivo protein landscape of the mouse DCT during high dietary K or low dietary Na intake.

Am J Physiol Renal Physiol 2021 May 29;320(5):F908-F921. Epub 2021 Mar 29.

Department of Biomedicine, Faculty of Health Sciences, Aarhus University, Aarhus, Denmark.

The hormone aldosterone is essential for maintaining K and Na balance and controlling blood pressure. Aldosterone has different effects if it is secreted due to hypovolemia or hyperkalemia. The kidney distal convoluted tubule (DCT) is believed to play a central role in mediating the differential responses to aldosterone. To determine the alterations in the DCT that may be responsible for these effects, male mice with green fluorescent protein expression specifically in the DCT were maintained on diets containing low NaCl (hypovolemic state) or high potassium citrate (hyperkalemic state) for 4 days, and DCT cells were isolated using fluorescence-activated cell sorting. This pure population of DCT cells was subjected to analysis by liquid chromatography-coupled tandem mass spectrometry. Over 3,000 proteins were identified in the DCT, creating the first proteome of the mouse DCT. Of the identified proteins, 210 proteins were altered in abundance following a low-NaCl diet and 625 proteins following the high-K diet. Many of these changes were not detectable by analyzing whole kidney samples from the same animals. When comparing responses to high-K versus low-Na diets, protein translation, chaperone-mediated protein folding, and protein ubiquitylation were likely to be significantly altered in the DCT subsequent to a high-K diet. In conclusion, this study defines an in vivo protein landscape of the DCT in male mice following either a low-NaCl or a high-K diet and acts as an essential resource for the kidney research community. The mineralocorticoid aldosterone, essential for maintaining body K and Na balance, has different effects if secreted due to hypovolemia or hyperkalemia. Here, we used proteomics to profile kidney distal convoluted tubule (DCT) cells isolated by a novel FACS approach from mice fed a low-Na diet (mimicking hypovolemia) or a high-K diet (mimicking hyperkalemia). The study provides the first in-depth proteome of the mouse DCT and insights into how it is physiologically regulated.
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http://dx.doi.org/10.1152/ajprenal.00064.2021DOI Listing
May 2021

Interactions Between Neutrophils and Periodontal Pathogens in Late-Onset Periodontitis.

Front Cell Infect Microbiol 2021 12;11:627328. Epub 2021 Mar 12.

State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, National Clinical Research Center for Oral Diseases, Sichuan University, Chengdu, China.

Late-onset periodontitis is associated with a series of inflammatory reactions induced by periodontal pathogens, such as , a keystone pathogen involved in periodontitis. Neutrophils are the most abundant leukocytes in the periodontal pocket/gingival crevice and inflamed periodontal tissues. They form a "wall" between the dental plaque and the junctional epithelium, preventing microbial invasion. The balance between neutrophils and the microbial community is essential to periodontal homeostasis. Excessive activation of neutrophils in response to periodontal pathogens can induce tissue damage and lead to periodontitis persistence. Therefore, illuminating the interactions between neutrophils and periodontal pathogens is critical for progress in the field of periodontitis. The present review aimed to summarize the interactions between neutrophils and periodontal pathogens in late-onset periodontitis, including neutrophil recruitment, neutrophil mechanisms to clear the pathogens, and pathogen strategies to evade neutrophil-mediated elimination of bacteria. The recruitment is a multi-step process, including tethering and rolling, adhesion, crawling, and transmigration. Neutrophils clear the pathogens mainly by phagocytosis, respiratory burst responses, degranulation, and neutrophil extracellular trap (NET) formation. The mechanisms that pathogens activate to evade neutrophil-mediated killing include impairing neutrophil recruitment, preventing phagocytosis, uncoupling killing from inflammation, and resistance to ROS, degranulation products, and NETs.
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http://dx.doi.org/10.3389/fcimb.2021.627328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994856PMC
March 2021

Viral etiology and epidemiology of pediatric patients hospitalized for acute respiratory tract infections in Macao: a retrospective study from 2014 to 2017.

BMC Infect Dis 2021 Mar 26;21(1):306. Epub 2021 Mar 26.

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao SAR, China.

Background: Acute respiratory infections (ARIs) are among the leading causes of hospitalization in children. Understanding the local dominant viral etiologies is important to inform infection control practices and clinical management. This study aimed to investigate the viral etiology and epidemiology of respiratory infections among pediatric inpatients in Macao.

Methods: A retrospective study using electronic health records between 2014 and 2017 at Kiang Wu Hospital was performed. Nasopharyngeal swab specimens were obtained from hospitalized children aged 13 years or younger with respiratory tract diseases. xMAP multiplex assays were employed to detect respiratory agents including 10 respiratory viruses. Data were analyzed to describe the frequency and seasonality.

Results: Of the 4880 children enrolled in the study, 3767 (77.1%) were positive for at least one of the 13 viral pathogens tested, of which 2707 (55.5%) being male and 2635 (70.0%) under 2 years old. Among the positive results, there were 3091 (82.0%) single infections and 676 (18.0%) multiple infections. The predominant viruses included human rhinovirus/enterovirus (HRV/EV 27.4%), adenovirus (ADV, 15.8%), respiratory syncytial virus B (RSVB, 7.8%) and respiratory syncytial virus A (RSVA, 7.8%). The detection of viral infection was the most prevalent in autumn (960/1176, 81.6%), followed by spring (1095/1406, 77.9%), winter (768/992, 77.4%), and summer (944/1306, 72.3%), with HRV/EV and ADV being most commonly detected throughout the 4 years of study period. The detection rate of viral infection was highest among ARI patients presented with croup (123/141, 87.2%), followed by lower respiratory tract infection (1924/2356, 81.7%) and upper respiratory tract infection (1720/2383, 72.2%). FluA, FluB and ADV were positive factors for upper respiratory tract infections. On the other hand, infection with RSVA, RSVB, PIV3, PIV4, HMPV, and EV/RHV were positively associated with lower respiratory tract infections; and PIV1, PIV2, and PIV3 were positively associated with croup.

Conclusions: This is the first study in Macao to determine the viral etiology and epidemiology of pediatric patients hospitalized for ARIs. The study findings can contribute to the awareness of pathogen, appropriate preventative measure, accurate diagnosis, and proper clinical management of respiratory viral infections among children in Macao.
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http://dx.doi.org/10.1186/s12879-021-05996-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995389PMC
March 2021

The contribution of infection to clinical outcomes in bronchiectasis: a prospective cohort study.

Ann Med 2021 12;53(1):459-469

Department of Respiratory and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.

Objectives: The impact of on the prognosis of bronchiectasis remains controversial. This study aimed to explore the prognostic value of in adult patients with bronchiectasis in central-southern China.

Patients And Methods: This prospective cohort study enrolled 1,234 patients with bronchiectasis between 2013 and 2019. The independent impact of on all-cause mortality, annual exacerbations, and hospitalizations was assessed.

Results: was isolated from 244 patients (19.8%). A total of 188 patients died over a follow-up period of 16 (1-36) months. Patients with had a longer disease course, poorer lung function, more lung lobe involvement, and more severe Bronchiectasis Severity Index (BSI) stage than those without . The independent impact of was observed on frequent hospitalizations but not on mortality and frequent exacerbations. Moderate- or high-risk comorbidities increased the risk of mortality (hazard ratio [HR]: 1.93, 95% confidence interval [CI]: 1.26-2.95), and this effect was magnified by the presence of (HR: 2.11, 95% CI: 1.28-3.48).

Conclusions: infection acts as a marker of disease severity as well as predictor of frequent hospitalizations. had no independent effect on all-cause mortality. combined with moderate- or high-risk comorbidities posed an increased risk of mortality. The management of comorbidities may be a critical target during the treatment of infection in bronchiectasis.KEY MESSAGE: increased the risk of frequent hospitalizations; however, it had no independent impact on all-cause mortality. combined with moderate- or high-risk comorbidities posed an increased risk of mortality.The management of comorbidities may be a critical target during the treatment of infection in bronchiectasis.
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http://dx.doi.org/10.1080/07853890.2021.1900594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993380PMC
December 2021

Identification and characteristics of the three subgroups of pain in Chinese children and adolescents with cancer.

J Pediatr Nurs 2021 Mar 19. Epub 2021 Mar 19.

School of Nursing, Fudan University, Shanghai, China. Electronic address:

Purpose: Pain is a distressing symptom for children and adolescents with cancer and is experienced by individuals differently. This study sought to determine subgroups according to their pain experiences, and how demographic, clinical, and quality of life (QOL)-related characteristics might differ across subgroups.

Design And Methods: This cross-sectional study recruited 187 pediatric patients with cancer aged 8 to 17 years old and asked them to complete measures of pain intensity, pain duration, pain interference and pain control using the Chinese translation of the validated questionnaire from the Pain Squad app, as well as 7 PROMIS measures assessing QOL-related outcomes. Latent profile analysis (LPA) was used to identify latent subgroups.

Results: Three subgroups of children were identified: low-pain/low-duration (69.5%), moderate-pain/high-duration (19.8%), and high-pain/moderate-duration (10.7%). Hospitalized children were more likely to be in the moderate-pain/high-duration subgroup. Children in the high-pain/moderate-duration subgroup were more likely to be cared for by unemployed caregivers. Scores on depressive symptoms (p = 0.002), anger (p < 0.001), anxiety (p = 0.045), fatigue (p = 0.044), and mobility (p = 0.008) questionnaire were significantly worse in the high-pain/moderate-duration subgroup than the other two subgroup.

Practice Implications: This study provides a scientific foundation for further studies exploring predictive factors related to pain experiences. More targeted treatment strategies targeting the specific characteristics of each subgroup will help improve patients' QOL and use of medical resources.

Conclusions: The 3 identified pain subgroups demonstrate the heterogeneity in pain experiences among pediatric patients with cancer. Knowledge of these subgroups can assist clinicians in better identifying and targeting pain treatment for children with cancer.
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http://dx.doi.org/10.1016/j.pedn.2021.01.015DOI Listing
March 2021

Ecotoxicity Risk of Low-Dose Methylmercury Exposure to : Multigenerational Toxicity and Population Discrepancy.

Chem Res Toxicol 2021 Apr 19;34(4):1114-1123. Epub 2021 Mar 19.

Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Key Laboratory of Environmental Toxicology and Pollution Control Technology of Anhui Province, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.

Methylmercury (MeHg) is a common organic form of mercury in water, which has been linked to several forms of biological toxicity. However, studies on the ecotoxicity risk of long-term exposure to low-dose MeHg are insufficient for the assessment of environmental safety. In the present study, the effects of MeHg on multiple generations (P0-F3) and population of were investigated under long-term, low-dose exposure. We investigated the multigenerational toxicity of MeHg by analyzing reproductive and developmental indicators. According to our results, exposure to 100 nM MeHg had little effect on the parental generation (P0) but caused serious reproductive toxicity in the offspring (F1-F3), and the effect of MeHg was aggravated with each passing generation. The genes related to apoptosis and DNA damage were upregulated in the F3 generation. Pearson correlation analysis showed that the changes in these genes were closely related to the apoptosis of gonadal cells. Furthermore, chronic exposure to MeHg (from 100 to 1000 nM group) caused a sharp decline in population size and triggered the "bag of worms" phenotype. Genes related to vulvar development were downregulated in the F3 generation after treatment with 100 nM MeHg. These data suggest that long-term low-dose MeHg exposure adversely affected and its offspring and triggered multigenerational toxicity and population discrepancy.
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http://dx.doi.org/10.1021/acs.chemrestox.0c00518DOI Listing
April 2021