Publications by authors named "Rui Xiao"

466 Publications

Transport Modeling of Locally Photogenerated Excitons in Halide Perovskites.

J Phys Chem Lett 2021 Apr 19:3951-3959. Epub 2021 Apr 19.

Department of Physics and Astronomy, University of California-Davis, One Shields Avenue, Davis, California 95616, United States.

Excitons have fundamental impacts on optoelectronic properties of semiconductors. Halide perovskites, with long carrier lifetimes and ionic crystal structures, may support highly mobile excitons because the dipolar nature of excitons suppresses phonon scattering. Inspired by recent experimental progress, we perform device modeling to rigorously analyze exciton formation and transport in methylammonium lead triiodide under local photoexcitation by using a finite element method. Mobile excitons, coexisting with free carriers, can dominate photocurrent generation at low temperatures. The simulation results are in excellent agreement with the experimentally observed strong temperature and gate dependence of carrier diffusion. This work signifies that efficient exciton transport can substantially influence charge transport in the family of perovskite materials.
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http://dx.doi.org/10.1021/acs.jpclett.1c00507DOI Listing
April 2021

Could preoxidation always promote the subsequent hydroconversion of lignin? Two counterexamples catalyzed by Cu/CuMgAlO in supercritical ethanol.

Bioresour Technol 2021 Apr 9;332:125142. Epub 2021 Apr 9.

Key Laboratory of Energy Thermal Conversion and Control of Ministry of Education, School of Energy and Environment, Southeast University, Nanjing 210096, PR China; Key Laboratory of Renewable Energy, Guangzhou Institute of Energy Conversion, Chinese Academy of Sciences, Guangzhou 510640, PR China. Electronic address:

In this study, two counterexamples of lignin preoxidation-hydroconversion were reported. First, two lignin feedstocks were preoxidized with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in acetonitrile with various dosages (15%, 30%, and 60%). Then, these preoxidized lignins (HELOs and MWLOs) were hydroconverted in supercritical ethanol catalyzed by Cu/CuMgAlO. Total yields from HELOs were all higher than those from HEL, indicating the good promotion of DDQ preoxidation on the subsequent hydroconversion of HELOs, especially with the DDQ dosage of 15%. Differently, the promotion effect of DDQ preoxidation on the hydroconversion of MWLOs depended on the DDQ dosage as well as the reaction time. Through the comparison of two counterexamples, this work bursted the myth that preoxidation can always promote the subsequent hydroconversion of lignin, revealed the influence of lignin property, preoxidation degree, and reaction conditions on the subsequent hydroconversion of preoxidized lignin, and presented the new insight into the preoxidation-hydroconversion strategy for lignin.
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http://dx.doi.org/10.1016/j.biortech.2021.125142DOI Listing
April 2021

Heterozygous variants in SPTBN1 cause intellectual disability and autism.

Am J Med Genet A 2021 Apr 13. Epub 2021 Apr 13.

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA.

Spectrins are common components of cytoskeletons, binding to cytoskeletal elements and the plasma membrane, allowing proper localization of essential membrane proteins, signal transduction, and cellular scaffolding. Spectrins are assembled from α and β subunits, encoded by SPTA1 and SPTAN1 (α) and SPTB, SPTBN1, SPTBN2, SPTBN4, and SPTBN5 (β). Pathogenic variants in various spectrin genes are associated with erythroid cell disorders (SPTA1, SPTB) and neurologic disorders (SPTAN1, SPTBN2, and SPTBN4), but no phenotypes have been definitively associated with variants in SPTBN1 or SPTBN5. Through exome sequencing and case matching, we identified seven unrelated individuals with heterozygous SPTBN1 variants: two with de novo missense variants and five with predicted loss-of-function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities). Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4/6) and epilepsy (2/7) or abnormal electroencephalogram without overt seizures (1/7) were present in a subset. Identification of loss-of-function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis. Our findings support the essential roles of SPTBN1 in human neurodevelopment and expand the knowledge of human spectrinopathy disorders.
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http://dx.doi.org/10.1002/ajmg.a.62201DOI Listing
April 2021

Effects of rhBMP-2 on Bone Formation Capacity of Rat Dental Stem/Progenitor Cells from Dental Follicle and Alveolar Bone Marrow.

Stem Cells Dev 2021 Apr 7;30(8):441-457. Epub 2021 Apr 7.

Institute of Stomatology, First Medical Center of Chinese PLA General Hospital, Beijing, China.

Dental stem/progenitor cells are a promising cell sources for alveolar bone (AB) regeneration because of their same embryonic origin and superior osteogenic potential. However, their molecular processes during osteogenic differentiation remain unclear. The objective of this study was to identify the responsiveness of dental follicle cells (DFCs) and AB marrow-derived mesenchymal stem cells (ABM-MSCs) to recombinant human bone morphogenetic protein-2 (rhBMP-2). These cells expressed vimentin and MSC markers and did not express cytokeratin and hematopoietic stem cell markers and showed multilineage differentiation potential under specific culture conditions. DFCs exhibited higher proliferation and colony-forming unit-fibroblast efficiency than ABM-MSCs; rhBMP-2 induced DFCs to differentiate toward a cementoblast/osteoblast phenotype and ABM-MSCs to differentiate only toward a osteoblast phenotype; and rhBMP-2-induced DFCs exhibited higher osteogenic differentiation potential than ABM-MSCs. These cells adhered, grew, and produced extracellular matrix on nanohydroxyapatite/collagen/poly(l-lactide) (nHAC/PLA). During a 14-day culture on nHAC/PLA, the extracellular alkaline phosphatase (ALP) activity of DFCs decreased gradually and that of ABM-MSCs increased gradually; rhBMP-2 enhanced their extracellular ALP activity, intracellular osteocalcin (OCN), and osteopontin (OPN) protein expression; and DFCs exhibited higher extracellular ALP activity and intracellular OCN protein expression than ABM-MSCs. When implanted subcutaneously in severe combined immunodeficient mice for 3 months, DFCs+nHAC/PLA+rhBMP-2 obtained higher percentage of bone formation area, OCN, and cementum attachment protein expression and lower OPN expression than ABM-MSCs+nHAC/PLA+rhBMP-2. These results showed that DFCs possessed superior proliferation and osteogenic differentiation potential in vitro, and formed higher quantity and quality bones in vivo. It suggested that DFCs might exhibit a more sensitive responsiveness to rhBMP-2, so that DFCs enter a relatively mature stage of osteogenic differentiation earlier than ABM-MSCs after rhBMP-2 induction. The findings imply that these dental stem/progenitor cells are alternative sources for AB engineering in regenerative medicine, and developing dental tissue may provide better source for stem/progenitor cells.
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http://dx.doi.org/10.1089/scd.2020.0170DOI Listing
April 2021

Hybrid genome de novo assembly with methylome analysis of the anaerobic thermophilic subsurface bacterium Thermanaerosceptrum fracticalcis strain DRI-13.

BMC Genomics 2021 Mar 23;22(1):209. Epub 2021 Mar 23.

Department of Microbiology, Southern Illinois University Carbondale, Carbondale, IL, USA.

Background: There is a dearth of sequenced and closed microbial genomes from environments that exceed > 500 m below level terrestrial surface. Coupled with even fewer cultured isolates, study and understanding of how life endures in the extreme oligotrophic subsurface environments is greatly hindered. Using a de novo hybrid assembly of Illumina and Oxford Nanopore sequences we produced a circular genome with corresponding methylome profile of the recently characterized thermophilic, anaerobic, and fumarate-respiring subsurface bacterium, Thermanaerosceptrum fracticalcis, strain DRI-13 to understand how this microorganism survives the deep subsurface.

Results: The hybrid assembly produced a single circular genome of 3.8 Mb in length with an overall GC content of 45%. Out of the total 4022 annotated genes, 3884 are protein coding, 87 are RNA encoding genes, and the remaining 51 genes were associated with regulatory features of the genome including riboswitches and T-box leader sequences. Approximately 24% of the protein coding genes were hypothetical. Analysis of strain DRI-13 genome revealed: 1) energy conservation by bifurcation hydrogenase when growing on fumarate, 2) four novel bacterial prophages, 3) methylation profile including 76.4% N6-methyladenine and 3.81% 5-methylcytosine corresponding to novel DNA methyltransferase motifs. As well a cluster of 45 genes of unknown protein families that have enriched DNA mCpG proximal to the transcription start sites, and 4) discovery of a putative core of bacteriophage exclusion (BREX) genes surrounded by hypothetical proteins, with predicted functions as helicases, nucleases, and exonucleases.

Conclusions: The de novo hybrid assembly of strain DRI-13 genome has provided a more contiguous and accurate view of the subsurface bacterium T. fracticalcis, strain DRI-13. This genome analysis reveals a physiological focus supporting syntrophy, non-homologous double stranded DNA repair, mobility/adherence/chemotaxis, unique methylome profile/recognized motifs, and a BREX defense system. The key to microbial subsurface survival may not rest on genetic diversity, but rather through specific syntrophy niches and novel methylation strategies.
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http://dx.doi.org/10.1186/s12864-021-07535-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988955PMC
March 2021

Machine learning models to predict electroencephalographic seizures in critically ill children.

Seizure 2021 Apr 4;87:61-68. Epub 2021 Mar 4.

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, United States; Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, United States. Electronic address:

Objective: To determine whether machine learning techniques would enhance our ability to incorporate key variables into a parsimonious model with optimized prediction performance for electroencephalographic seizure (ES) prediction in critically ill children.

Methods: We analyzed data from a prospective observational cohort study of 719 consecutive critically ill children with encephalopathy who underwent clinically-indicated continuous EEG monitoring (CEEG). We implemented and compared three state-of-the-art machine learning methods for ES prediction: (1) random forest; (2) Least Absolute Shrinkage and Selection Operator (LASSO); and (3) Deep Learning Important FeaTures (DeepLIFT). We developed a ranking algorithm based on the relative importance of each variable derived from the machine learning methods.

Results: Based on our ranking algorithm, the top five variables for ES prediction were: (1) epileptiform discharges in the initial 30 minutes, (2) clinical seizures prior to CEEG initiation, (3) sex, (4) age dichotomized at 1 year, and (5) epileptic encephalopathy. Compared to the stepwise selection-based approach in logistic regression, the top variables selected by our ranking algorithm were more informative as models utilizing the top variables achieved better prediction performance evaluated by prediction accuracy, AUROC and F1 score. Adding additional variables did not improve and sometimes worsened model performance.

Conclusion: The ranking algorithm was helpful in deriving a parsimonious model for ES prediction with optimal performance. However, application of state-of-the-art machine learning models did not substantially improve model performance compared to prior logistic regression models. Thus, to further improve the ES prediction, we may need to collect more samples and variables that provide additional information.
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http://dx.doi.org/10.1016/j.seizure.2021.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044039PMC
April 2021

Study on the effect of Mongolian medicine Qiwei Qinggan Powder on hepatic fibrosis through JAK2/STAT3 pathway.

Biosci Biotechnol Biochem 2021 Mar;85(4):775-785

Department of Pharmacology, School of Basic Medicine, Inner Mongolia Medical University, Hohhot, China.

This research aimed to evaluate the antihepatic fibrosis effect and explore the mechanism of Qiwei Qinggan Powder (QGS-7) in vivo and in vitro. Carbon tetrachloride (CCl4)-treated rats and hepatic stellate cells (HSCs) were used. QGS-7 treatment significantly improved the liver function of rats as indicated by decreased serum enzymatic activities of alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. Meanwhile, the hydroxyproline of liver was significantly decreased. Histopathological results indicated that QGS-7 alleviated liver damage and reduced the formation of fibrosis septa. Moreover, QGS-7 significantly attenuated expressions of Alpha smooth muscle actin, Collagen I, Janus kinase 2 (JAK2), phosphorylation-JAK2, signal transducer and activator of transcription 3 (STAT3), phosphorylation-STAT3 in the rat hepatic fibrosis model. QGS-7 inhibited HSC proliferation and promoted it apoptosis. QGS-7 may affect hepatic fibrosis through JAK2/STAT3 signaling pathway so as to play an antihepatic fibrosis role.
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http://dx.doi.org/10.1093/bbb/zbab001DOI Listing
March 2021

Prevalence of asthma in hospitalized and non-hospitalized children with COVID-19.

J Allergy Clin Immunol Pract 2021 Mar 3. Epub 2021 Mar 3.

PolicyLab and Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, Pa; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pa; Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pa. Electronic address:

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http://dx.doi.org/10.1016/j.jaip.2021.02.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927636PMC
March 2021

Detecting cell-type-specific allelic expression imbalance by integrative analysis of bulk and single-cell RNA sequencing data.

PLoS Genet 2021 Mar 4;17(3):e1009080. Epub 2021 Mar 4.

Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.

Allelic expression imbalance (AEI), quantified by the relative expression of two alleles of a gene in a diploid organism, can help explain phenotypic variations among individuals. Traditional methods detect AEI using bulk RNA sequencing (RNA-seq) data, a data type that averages out cell-to-cell heterogeneity in gene expression across cell types. Since the patterns of AEI may vary across different cell types, it is desirable to study AEI in a cell-type-specific manner. Although this can be achieved by single-cell RNA sequencing (scRNA-seq), it requires full-length transcript to be sequenced in single cells of a large number of individuals, which are still cost prohibitive to generate. To overcome this limitation and utilize the vast amount of existing disease relevant bulk tissue RNA-seq data, we developed BSCET, which enables the characterization of cell-type-specific AEI in bulk RNA-seq data by integrating cell type composition information inferred from a small set of scRNA-seq samples, possibly obtained from an external dataset. By modeling covariate effect, BSCET can also detect genes whose cell-type-specific AEI are associated with clinical factors. Through extensive benchmark evaluations, we show that BSCET correctly detected genes with cell-type-specific AEI and differential AEI between healthy and diseased samples using bulk RNA-seq data. BSCET also uncovered cell-type-specific AEIs that were missed in bulk data analysis when the directions of AEI are opposite in different cell types. We further applied BSCET to two pancreatic islet bulk RNA-seq datasets, and detected genes showing cell-type-specific AEI that are related to the progression of type 2 diabetes. Since bulk RNA-seq data are easily accessible, BSCET provides a convenient tool to integrate information from scRNA-seq data to gain insight on AEI with cell type resolution. Results from such analysis will advance our understanding of cell type contributions in human diseases.
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http://dx.doi.org/10.1371/journal.pgen.1009080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7963069PMC
March 2021

Dietary Geranylgeranyl Pyrophosphate Counteracts the Benefits of Statin Therapy in Experimental Pulmonary Hypertension.

Circulation 2021 Mar 4. Epub 2021 Mar 4.

Department of Pathophysiology, School of Basic Medicine; Key Laboratory of Pulmonary Diseases of Ministry of Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The mevalonate pathway generates endogenous cholesterol and intermediates including geranylgeranyl pyrophosphate (GGPP). By reducing GGPP production, statins exert pleiotropic or cholesterol-independent effects. The potential regulation of GGPP homeostasis through dietary intake and the interaction with concomitant statin therapy is unknown. We developed a sensitive HPLC technique to quantify dietary GGPP and conducted proteomics, qRT-PCR screening and western blot to determine signaling cascades, gene expression, protein-protein interaction and protein membrane trafficking in wild type and transgenic rats. GGPP contents were highly variable depending on food source that differentially regulated blood GGPP levels in rats. Diets containing intermediate and high GGPP reduced or abolished the effects of statins in rats with hypoxia- and monocrotaline-induced pulmonary hypertension: this was rescuable by methyl-allylthiosulfinate and methyl-allylthiosulfinate-rich garlic extracts. In human pulmonary artery smooth muscle cells (HPASMCs) treated with statins, hypoxia activated RhoA in an extracellular GGPP-dependent manner. Hypoxia-induced ROCK2/Rab10 signaling was prevented by statin and recovered by exogenous GGPP. The hypoxia-activated RhoA/ROCK2 pathway in rat and HPASMCs upregulated the expression of Ca-sensing receptor (CaSR) and hypoxia-induced mitogenic factor/FIZZ1 (HIMF), a mechanism attenuated by statin treatment and regained with exogenous GGPP. Rab10-knockdown almost abrogated hypoxia-promoted CaSR membrane-trafficking, a process diminished by statin and resumed by exogenous GGPP. Hypoxia-induced pulmonary hypertension was reduced in rats with CaSR mutated at the binding motif of HIMF and the interaction between dietary GGPP and statin efficiency was abolished. In humans fed with a high GGPP diet, blood GGPP levels were increased, and this abolished statin-lowering effects on plasma GGPP and hypoxia-enhanced RhoA activity of blood monocytes that were both also rescued by garlic extracts. There is important dietary regulation of GGPP levels that interferes with the effects of statin therapy in experimental pulmonary hypertension. These observations rely on a key and central role of i) RhoA-ROCK2 cascade activation and ii) Rab10-faciliated CaSR membrane trafficking with iii) subsequent overexpression and binding of HIMF to CaSR. These findings warrant clinical investigation for the treatment of pulmonary hypertension and perhaps other diseases by combining statin together with garlic-derived methyl-allylthiosulfinate or garlic extracts and thus circumventing dietary GGPP variations.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.046542DOI Listing
March 2021

Effects of Different Local Analgesic Techniques on Postoperative Quality of Life and Pain in Patients Undergoing Total Hip Arthroplasty Under General Anesthesia: A Randomized Controlled Trial.

J Pain Res 2021 24;14:527-536. Epub 2021 Feb 24.

Department of Anesthesiology, First Affiliated Hospital, Anhui Medical University, Hefei, Anhui, 230022, People's Republic of China.

Background: Both lumbosacral plexus block (LSPB) and local infiltration analgesia (LIA) can provide postoperative analgesia for patients undergoing total hip arthroplasty (THA). The current study aimed to compare the differences between LSPB and LIA on postoperative pain and quality of life (QoL) in THA patients.

Methods: A total of 117 patients aged 40-80 years, ASA I-III, were prospectively randomized into two groups: a general anesthesia plus LSPB (Group LSPB) and a general anesthesia plus LIA (Group LIA). Pain intensity and opioid consumption were recorded Within 72 hours after surgery. QoL was measured by EQ-5D and EQ-VAS questionnaires, and the incidence of postoperative pain was measured as part of the EQ-5D on day 1, day 3, day 7, and month 1, month 3, and month 6 after surgery.

Results: EQ-5D scores: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression were higher in Group LSPB versus Group LIA throughout six-month follow-ups (p = 0.039). The pain intensity was lower in Group LSPB than in Group LIA 0-12 h after surgery (2.41 vs 2.79, p = 0.01), but was higher in Group LSPB than in Group LIA 12-24 h (2.59 vs 2.05, p = 0.02) and 24-48 h (2.18 vs 1.73, p = 0.02) after surgery. There were no differences in opioid consumption between the groups during the first 72 postoperative hours. In the first month after surgery, more patients in Group LSPB than in Group LIA had no pain (52 vs 40, p = 0.04).

Conclusion: Both LSPB and LIA can provide satisfactory postoperative analgesia. The LSPB is better than LIA for long-term QoL in THA patients undergoing general anesthesia.

Clinical Trial Registration Number: The Chinese Clinical Trial Registry (ChiCTR-INR-17012545).
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http://dx.doi.org/10.2147/JPR.S289018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917318PMC
February 2021

Combinatorial glucose, nicotinic acid, and N-acetylcysteine therapy has synergistic effect in preclinical C. elegans and zebrafish models of mitochondrial complex I disease.

Hum Mol Genet 2021 Feb 27. Epub 2021 Feb 27.

Mitochondrial Medicine Frontier Program, Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA.

Mitochondrial respiratory chain disorders are empirically managed with variable antioxidant, cofactor, and vitamin 'cocktails'. However, clinical trial validated and approved compounds, or doses, do not exist for any single or combinatorial mitochondrial disease therapy. Here, we sought to pre-clinically evaluate whether rationally-designed mitochondrial medicine combinatorial regimens might synergistically improve survival, health, and physiology in translational animal models of respiratory chain complex I disease. Having previously demonstrated that gas-1(fc21) complex I subunit NDUFS2-/-  C. elegans have short lifespan that can be significantly rescued with 17 different metabolic modifiers, signaling modifiers, or antioxidants, here we evaluated 11 random combinations of these 3 treatment classes on gas-1(fc21) lifespan. Synergistic rescue occurred only with glucose, nicotinic acid, and N-acetylcysteine (Glu + NA + NAC), yielding improved mitochondrial membrane potential that reflects integrated respiratory chain function, without exacerbating oxidative stress and while reducing mitochondrial stress (UPRmt) and improving intermediary metabolic disruptions at the levels of the transcriptome, steady-state metabolites, and intermediary metabolic flux. Equimolar Glu + NA + NAC dosing in a zebrafish vertebrate model of rotenone-based complex I inhibition synergistically rescued larval activity, brain death, lactate, ATP, and glutathione levels. Overall, these data provide objective preclinical evidence in two evolutionary-divergent animal models of mitochondrial complex I disease to demonstrate that combinatorial Glu + NA + NAC therapy significantly improved animal resiliency in the face of stressors that exacerbate their underlying metabolic deficiency, thereby preventing acute neurologic and biochemical decompensation. Clinical trials are warranted to evaluate the efficacy of this lead combinatorial therapy regimen to improve resiliency and health outcomes in human subjects with mitochondrial disease.
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http://dx.doi.org/10.1093/hmg/ddab059DOI Listing
February 2021

Comprehensive Analysis of LncRNA-mRNA Expression Profiles and the ceRNA Network Associated with Pyroptosis in LPS-Induced Acute Lung Injury.

J Inflamm Res 2021 17;14:413-428. Epub 2021 Feb 17.

Department of Intensive Care Unit, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, 330000, People's Republic of China.

Purpose: To explore the molecular mechanism and search for candidate lncRNA and mRNA associated with pyroptosis in the gene expression profile of LPS-induced acute lung injury (ALI).

Methods: We investigated lncRNA and mRNA expression in lipopolysaccharide (LPS)-induced ALI at an early stage. RNA sequencing (RNA-Seq) was carried out to analyze lncRNA and mRNA expression profiles between the LPS-induced and control groups. We used bioinformatics analysis to predict target genes of early differential lncRNAs among obtained the differential mRNAs.

Results: A total of 78 lncRNAs and 248 mRNAs were upregulated at 2 hours and downregulated at 9 hours, and 21 lncRNAs and 107 mRNAs were downregulated at 2 and upregulated at 9 hours in early ALI models. We predicted 7 cis-and trans-regulated target genes of the top 20 lncRNAs. Gene Ontology (GO) analysis indicated that the target genes for the screened lncRNAs were most enriched in three-terms: regulation of protein serine/threonine kinase activity, pertussis, and cellular response to LPS. Additionally, target genes of lncRNAs were the top three enriched in pertussis, osteoclast differentiation, and cAMP signaling pathways with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We also identified vital mRNAs and lncRNAs. Protein-protein interaction (PPI) network analysis suggested that Tnf, Jun, and Atf3 were the top three key genes. Hub lncRNA4344 (NONRATT004344.2) and cis-regulated target mRNA (NLRP3) were validated in vitro. Finally, luciferase assay results confirmed that lncRNA4344 sponged miR-138-5p to promote pyroptosis in inflammatory responses to LPS-induced acute lung injury by targeting NLRP3.

Conclusion: Based on analysis of lncRNA and mRNA expression profiles by RNA-Seq and experimental verification, this study is the first to reveal that lncRNA4344 sponged miR-138-5p to promote pyroptosis in inflammatory responses of LPS-induced acute lung injury by targeting NLRP3. These newly identified lncRNA, miRNA, and mRNA might be novel potential targets for early treatment and prevention in early ALI.
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http://dx.doi.org/10.2147/JIR.S297081DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898231PMC
February 2021

Correlates of CGM Use Trajectories in Children and Adolescents with Type 1 Diabetes.

Diabetes Technol Ther 2021 Feb 19. Epub 2021 Feb 19.

Children's Hospital of Philadelphia, Endocrinology/diabetes, 34th St and Civic Center Blvd., Suite 1NW30, Philadelphia, Pennsylvania, United States, 19104;

The goal of this study was to characterize trajectories of CGM use in youth five through 12 weeks after starting CGM and examine what factors differentiate between the trajectory groups. Parent-youth dyads completed assessments before starting CGM. Days of CGM use between weeks 5 and 12 were accessed via cloud based data repository. Three patterns of use were observed among 96 youth (mean age 13.4±2.75 years; 75% white): Sustained High, Declining, and Sustained Low. Youth in the Sustained Low and Declining groups were more likely than those in the Sustained High group to use a receiver (versus smart phone). There were no differences between the trajectory groups with respect to age, race, ethnicity, income, or insulin regimen. Future research should examine trajectory groups over a longer follow-up period and identify baseline factors that reliably predict which youth will have low or declining CGM use over time.
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http://dx.doi.org/10.1089/dia.2020.0668DOI Listing
February 2021

Glass Transition Behavior of Wet Polymers.

Authors:
Hai Li Rui Xiao

Materials (Basel) 2021 Feb 4;14(4). Epub 2021 Feb 4.

Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province, Department of Engineering Mechanics, Zhejiang University, Hangzhou 310027, China.

We have performed a systematical investigation on the glass transition behavior of amorphous polymers with different solvent concentrations. Acrylate-based amorphous polymers are synthesized and treated by isopropyl alcohol to obtain specimens with a homogenous solvent distribution. The small strain dynamic mechanical tests are then performed to obtain the glass transition behaviors. The results show that the wet polymers even with a solvent concentration of more than 60 wt.% still exhibit a glass transition behavior, with the glass transition region shifting to lower temperatures with increasing solvent concentrations. A master curve of modulus as a function of frequency can be constructed for all the polymer-solvent systems via the time-temperature superposition principle. The relaxation time and the breadth of the relaxation spectrum are then obtained through fitting the master curve using a fractional Zener model. The results indicate that the breadth of the relaxation spectrum has been greatly expanded in the presence of solvents, which has been rarely reported in the literature. Thus, this work can potentially advance the fundamental understanding of the effects of solvent on the glass transition behaviors of amorphous polymers.
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http://dx.doi.org/10.3390/ma14040730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915364PMC
February 2021

In Situ Exosomal MicroRNA Determination by Target-Triggered SERS and FeO@TiO-Based Exosome Accumulation.

ACS Sens 2021 03 8;6(3):852-862. Epub 2021 Feb 8.

Beijing Key Laboratory of New Molecular Diagnosis Techniques for Infectious Dedication, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing 100850, P. R. China.

Exosomal microRNAs (miRNAs) have been proved to be important biomarkers for the early diagnosis of cancers. However, the accurate quantification of exosomal miRNAs is hampered either by laborious exosome isolation and lysis or by RNA extraction and the amplification process. Here, we reported an in situ platform for direct exosomal miRNAs from serum samples. First, locked nucleic acid (LNA)-modified Au@DTNB (DTNB is the Raman reporter molecule 5,5'-dithiobis-(2-nitrobenzoic acid)) was synthesized as surface-enhanced Raman scattering (SERS) tags to enter into exosomes and assemble with target miRNAs to induce hot-spot SERS signals. Second, FeO@TiO nanoparticles were added to enrich the exosomes through affinity interaction of the TiO shell for further SERS detection. Based on the platform, target miRNAs can be directly qualified in situ with a detection limit of 0.21 fM, which is better or comparable with quantitative reverse transcription polymerase chain reaction (qRT-PCR) and other in situ methods reported before. Moreover, neither capture antibody nor ultracentrifugation pretreatment was needed in the whole detection procedure. Using exosomal miRNA-10b as a proof of concept, pancreatic ductal adenocarcinoma (PDAC) patients can be recognized from normal controls (NCs) with an accuracy of 99.6%. The simple and sensitive in situ exosomal miRNA detection assay can be seen as a noninvasive liquid biopsy assay for clinical cancer diagnostic adaption.
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http://dx.doi.org/10.1021/acssensors.0c01900DOI Listing
March 2021

Knockdown of Alpha-1 Antitrypsin with antisense oligonucleotide does not exacerbate smoke induced lung injury.

PLoS One 2021 4;16(2):e0246040. Epub 2021 Feb 4.

College of Physicians and Surgeons, Columbia University Medical Center, New York, New York, United States of America.

Alpha-1 Antitrypsin (AAT) is a serum protease inhibitor that regulates increased lung protease production induced by cigarette smoking. Mutations in the Serpina1 gene cause AAT to form hepatoxic polymers, which can lead to reduced availability for the protein's primary function and severe liver disease. An AAT antisense oligonucleotide (ASO) was previously identified to be beneficial for the AATD liver disease by blocking the mutated AAT transcripts. Here we hypothesized that knockdown of AAT aggravates murine lung injury during smoke exposure and acute exacerbations of chronic obstructive pulmonary disease (COPD). C57BL/6J mice were randomly divided into 4 groups each for the smoking and smoke-flu injury models. The ASO and control (No-ASO) were injected subcutaneously starting with smoking or four days prior to influenza infection and then injected weekly at 50 mg/kg body weight. ASO treatment during a 3-month smoke exposure significantly decreased the serum and lung AAT expression, resulting in increased Cela1 expression and elastase activity. However, despite the decrease in AAT, neither the inflammatory cell counts in the bronchoalveolar lavage fluid (BALF) nor the lung structural changes were significantly worsened by ASO treatment. We observed significant differences in inflammation and emphysema due to smoke exposure, but did not observe an ASO treatment effect. Similarly, with the smoke-flu model, differences were only observed between smoke-flu and room air controls, but not as a result of ASO treatment. Off-target effects or compensatory mechanisms may account for this finding. Alternatively, the reduction of AAT with ASO treatment, while sufficient to protect from liver injury, may not be robust enough to lead to lung injury. The results also suggest that previously described AAT ASO treatment for AAT mutation related liver disease may attenuate hepatic injury without being detrimental to the lungs. These potential mechanisms need to be further investigated in order to fully understand the impact of AAT inhibition on protease-antiprotease imbalance in the murine smoke exposure model.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246040PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861354PMC
February 2021

A novel role of the mitochondrial iron-sulfur cluster assembly protein ISCU-1/ISCU in longevity and stress response.

Geroscience 2021 Feb 1. Epub 2021 Feb 1.

Department of Aging and Geriatric Research, Institute on Aging, University of Florida, PO Box 100143, Gainesville, FL, 32610, USA.

As an ancient cellular co-factor ubiquitously present in all domains of life, nearly all iron-sulfur ([Fe-S]) clusters are assembled in the mitochondrion. Although multiple mitochondrion-derived signalings are known to be key players in longevity regulation, whether the mitochondrial [Fe-S] cluster assembly machinery modulates lifespan is previously unknown. Here, we find that ISCU-1, the C. elegans ortholog of the evolutionarily conserved iron-sulfur cluster (ISC) assembly machinery central protein ISCU, regulates longevity and stress response. Specifically, ISCU-1 accelerates aging in the intestine. Moreover, we identify the Nrf2 transcription factor SKN-1 and a nuclear hormone receptor NHR-49 as the downstream factors of ISCU-1. Lastly, a mitochondrial outer membrane protein phosphatase PGAM-5 appears to link ISCU-1 to SKN-1 and NHR-49 in lifespan regulation. Together, we have identified a novel function of mitochondrial ISC assembly machinery in longevity modulation and stress response.
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http://dx.doi.org/10.1007/s11357-021-00327-zDOI Listing
February 2021

Dissolved organic nitrogen in wastewater treatment processes: Transformation, biosynthesis and ecological impacts.

Environ Pollut 2021 Jan 6;273:116436. Epub 2021 Jan 6.

Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Environmental Resource Sciences, Zhejiang University, 310058, Hangzhou, China; State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, 150090, China. Electronic address:

With the upgrade of wastewater treatment plants (WWTPs) to meet more stringent discharge limits for nutrients, dissolved organic nitrogen (DON) is present at an increasing percentage (up to 85%) in the effluent. Discharged DON is of great environmental concern due to its potentials in stimulating algal growth and forming toxic nitrogenous disinfection by-products (N-DBPs). This article systematically reviewed the characteristics, transformation and ecological impacts of wastewater DON. Proteins, amino acids and humic substances are the abundant DON compounds, but a large fraction (nearly 50%) of DON remains uncharacterized. Biological treatment processes play a dominant role in DON transformation (65-90%), where DON serves as both nutrient and energy sources. Despite of the above progress, critical knowledge gaps remain in DON functional duality, relationship with dissolved inorganic nitrogen (DIN) species, and coupling/decoupling with the dissolved organic carbon (DOC) pool. Development of more rapid and accurate quantification methods, modeling transformation processes, and assessing DON-associated eutrophication and N-DBP formation risks should be given priority in further investigations.
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http://dx.doi.org/10.1016/j.envpol.2021.116436DOI Listing
January 2021

Impacts of organics on the microbial ecology of wastewater anammox processes: Recent advances and meta-analysis.

Water Res 2021 Mar 6;191:116817. Epub 2021 Jan 6.

Key Laboratory of Environment Remediation and Ecological Health, Ministry of Education, College of Environmental Resource Sciences, Zhejiang University, Hangzhou 310058, China; Zhejiang Province Key Laboratory for Water Pollution Control and Environmental Safety, Hangzhou 310058, China. Electronic address:

Anaerobic ammonium oxidation (anammox) represents a promising technology for wastewater nitrogen removal. Organics management is critical to achieving efficient and stable performance of anammox or integrated processes, e.g., denitratation-anammox. The aim of this systematic review is to synthesize the state-of-the-art knowledge on the multifaceted impacts of organics on wastewater anammox community structure and function. Both exogenous and endogenous organics are discussed with respect to their effects on the biofilm/granule structure and function, as well as the interactions between anammox bacteria (AnAOB) and a broad range of coexisting functional groups. A global core community consisting of 19 taxa is identified and a co-occurrence network is constructed by meta-analysis on the 16S rDNA sequences of 149 wastewater anammox samples. Correlations between core taxa, keystone taxa, and environmental factors, including COD, nitrogen loading rate (NLR) and C/N ratio are obtained. This review provides a holistic understanding of the microbial responses to different origins and types of organics in wastewater anammox reactors, which will facilitate the design and operation of more efficient anammox-based wastewater nitrogen removal process.
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http://dx.doi.org/10.1016/j.watres.2021.116817DOI Listing
March 2021

Functional crosstalk between Long non-coding RNAs and the NLRP3 inflammasome in the regulation of diseases.

Mol Immunol 2021 03 11;131:191-200. Epub 2021 Jan 11.

Department of Intensive Care Unit, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Dong Lake District, Nanchang, Jiangxi Province, 330000, China. Electronic address:

Emerging evidence has indicated that long noncoding RNAs (lncRNAs) are involved in various pathophysiological processes of disease, such as cancer occurrence, viral invasion, and inflammatory damage. The main inflammatory body component, nod-like receptor protein 3 (NLRP3), is the trigger point of inflammatory reactions and inflammation-related diseases and coordinates the body's response to inflammation. At present, increasing evidence shows that the interaction of lncRNAs and the NLRP3 inflammasome plays an important role in the inflammatory response and different diseases. This may be involved in the development and progression of various diseases by activating signalling pathways and a variety of molecular regulatory mechanisms-this article reviews progress in research on the relationship between lncRNAs and the NLRP3 inflammasome under different conditions.
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http://dx.doi.org/10.1016/j.molimm.2020.12.038DOI Listing
March 2021

Depressive symptoms and allostatic load have a bidirectional association among Puerto Rican older adults.

Psychol Med 2021 Jan 14:1-13. Epub 2021 Jan 14.

Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.

Background: Depression is strongly associated with chronic disease; yet, the direction of this relationship is poorly understood. Allostatic load (AL) provides a framework for elucidating depression-disease pathways. We aimed to investigate bidirectional, longitudinal associations of baseline depressive symptoms or AL with 5-year AL or depressive symptoms, respectively.

Methods: Data were from baseline, 2-year, and 5-year visits of 620 adults (45-75 years) enrolled in the Boston Puerto Rican Health Study. The Center for Epidemiology Studies Depression (CES-D) scale (0-60) captured depressive symptoms, which were categorized at baseline as low (<8), subthreshold (8-15), or depression-likely (⩾16) symptoms. AL was calculated from 11 parameters of biological functioning, representing five physiological systems. Baseline AL scores were categorized by the number of dysregulated parameters: low (0-2), moderate (3-5), or high (⩾6) AL. Multivariable, multilevel random intercept and slope linear regression models were used to examine associations between 3-category baseline CES-D score and 5-year continuous AL score, and between baseline 3-category AL and 5-year continuous CES-D score.

Results: Baseline subthreshold depressive symptoms [(mean (95% CI)): 4.8 (4.5-5.2)], but not depression-likely symptoms [4.5 (4.2-4.9)], was significantly associated with higher 5-year AL scores, compared to low depressive symptoms [4.3 (3.9-4.7)]. Baseline high AL [19.4 (17.6-21.2)], but not low AL [18.5 (16.5-20.6)], was significantly associated with higher 5-year CES-D score, compared to baseline moderate AL [16.9 (15.3-18.5)].

Conclusions: Depressive symptoms and AL had a bi-directional relationship over time, indicating a nuanced pathway linking depression with chronic diseases among a minority population.
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http://dx.doi.org/10.1017/S0033291720005139DOI Listing
January 2021

Fluoxetine ameliorates depressive symptoms by regulating lncRNA expression in the mouse hippocampus.

Zool Res 2021 Jan;42(1):28-42

State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medical Chemistry, Kunming Institute of Botany, the Chinese Academy of Sciences, Kunming, Yunnan 650201, China.

Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity. The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise. Recent studies have demonstrated that altered expressions of long non-coding RNAs (lncRNAs) in the brain affect neurodevelopment and manifest modulating functions during the depression. However, most lncRNAs have not yet been studied. Herein, we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors, as well as their corresponding response following antidepressant fluoxetine treatment. A chronic unpredictable mild stress (CUMS) mouse model was applied. A six-week fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors. In addition, differential expression analysis of lncRNAs was performed following RNA-sequencing. A total of 282 lncRNAs (134 up-regulated and 148 down-regulated) were differentially expressed in CUMS-induced mice relative to non-stressed counterparts ( <0.05). Moreover, 370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention. Gene Ontology (GO) analyses showed an association between significantly dysregulated lncRNAs and protein binding, oxygen binding, and transport activity, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways. Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus. The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840451PMC
January 2021

Fluoxetine ameliorates depressive symptoms by regulating lncRNA expression in the mouse hippocampus.

Zool Res 2021 Jan;42(1):28-42

State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medical Chemistry, Kunming Institute of Botany, the Chinese Academy of Sciences, Kunming, Yunnan 650201, China.

Depression is a prevalent mental disorder that is associated with aging and contributes to increased mortality and morbidity. The overall prevalence of geriatric depression with clinically significant symptoms is currently on the rise. Recent studies have demonstrated that altered expressions of long non-coding RNAs (lncRNAs) in the brain affect neurodevelopment and manifest modulating functions during the depression. However, most lncRNAs have not yet been studied. Herein, we analyzed the transcriptome of dysregulated lncRNAs to reveal their expressions in a mouse model exhibiting depressive-like behaviors, as well as their corresponding response following antidepressant fluoxetine treatment. A chronic unpredictable mild stress (CUMS) mouse model was applied. A six-week fluoxetine intervention in CUMS-induced mice attenuated depressive-like behaviors. In addition, differential expression analysis of lncRNAs was performed following RNA-sequencing. A total of 282 lncRNAs (134 up-regulated and 148 down-regulated) were differentially expressed in CUMS-induced mice relative to non-stressed counterparts ( <0.05). Moreover, 370 differentially expressed lncRNAs were identified in CUMS-induced mice after fluoxetine intervention. Gene Ontology (GO) analyses showed an association between significantly dysregulated lncRNAs and protein binding, oxygen binding, and transport activity, while the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these dysregulated lncRNAs might be involved in inflammatory response pathways. Fluoxetine effectively ameliorated the symptoms of depression in CUMS-induced mice by regulating the expression of lncRNAs in the hippocampus. The findings herein provide valuable insights into the potential mechanism underlying depression in elderly people.
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http://dx.doi.org/10.24272/j.issn.2095-8137.2020.294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840451PMC
January 2021

Characteristics of Very Low Frequency Sound Propagation in Full Waveguides of Shallow Water.

Sensors (Basel) 2020 Dec 30;21(1). Epub 2020 Dec 30.

Acoustic Science and Technology Laboratory, Harbin Engineering University, Harbin 150001, China.

This work is concerned with the characteristics of very low frequency sound propagation (VLF, ≤100 Hz) in the shallow marine environment. Under these conditions, the classical hypothesis of considering the sea bottom as a fluid environment is no longer appropriate, and the sound propagation characteristics at the sea bottom should be also considered. Hence, based on the finite element method (FEM), and setting the sea bottom as an elastic medium, a proposed model which unifies the sea water and sea bottom is established, and the propagation characteristics in full waveguides of shallow water can be synchronously discussed. Using this model, the effects of the sea bottom topography and the various geoacoustic parameters on VLF sound propagation and its corresponding mechanisms are investigated through numerical examples and acoustic theory. The simulation results demonstrate the adaptability of the proposed model to complex shallow water waveguides and the accuracy of the calculated acoustic field. For the sea bottom topography, the greater the inclination angle of an up-sloping sea bottom, the stronger the leak of acoustic energy to the sea bottom, and the more rapid the attenuation of the acoustic energy in sea water. The effect of a down-sloping sea bottom on acoustic energy is the opposite. Moreover, the greater the pressure wave (P-wave) speed in the sea bottom, the more acoustic energy remains in the water rather than leaking into the bottom; the influence laws of the density and the shear wave (S-wave) speed in the sea bottom are opposite.
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http://dx.doi.org/10.3390/s21010192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795552PMC
December 2020

[Progress in researches on spontaneously mutated mouse model of male infertility].

Authors:
Shuang Lu Rui Xiao

Zhonghua Nan Ke Xue 2020 May;26(5):468-471

Key Laboratory of Molecular Pathology of Inner Mongolia Autonomous Region, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010059, China.

Male infertility in animals are caused by many factors and mostly by genetic mutations. Spontaneously mutated mice have long been used as important animal models for basic medical researches on human genetic diseases and as valuable research tools for discovering new genes and their functions. Spontaneously mutated mice are often detected as random genetic events in zoos or research institutions that house large groups of mice, and they carry various phenotypes, some of which can cause male sterility. This review summarizes the types of spontaneously mutated mice carrying male infertility-related phenotypes to provide an animal model for the study of male infertility.
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May 2020

[Male infertility - related gene knockout mouse models].

Zhonghua Nan Ke Xue 2020 Apr;26(4):357-363

Key Laboratory of Molecular Pathology, Inner Mongolia Medical University, Hohhot, Inner Mongolia 010000, China .

The pathogenesis of male infertility is rather complicated. The establishment of animal models, especially mouse models, of male infertility, provides a model basis for the studies of the roles and molecular mechanisms of infertility-related genes. Currently there are mainly three types of mouse models for biomedical researches, namely, the mouse model made by the knockout, knock-in or gene capture method, transgenic mouse model, and chemically induced point mutant mouse model. This review summarizes male infertility - related gene knockout mouse models, aiming to find a suitable animal model for studying the pathogenesis of male infertility.
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April 2020

Distinct temporal actions of different types of unfolded protein responses during aging.

J Cell Physiol 2021 Jul 21;236(7):5069-5079. Epub 2020 Dec 21.

Department of Aging and Geriatric Research, College of Medicine, Institute on Aging, University of Florida, Gainesville, Florida, USA.

Proteotoxic stress is a common challenge for all organisms. Among various mechanisms involved in defending such stress, the evolutionarily conserved unfolded protein responses (UPRs) play a key role across species. Interestingly, UPRs can occur in different subcellular compartments including the endoplasmic reticulum (UPR ), mitochondria (UPR ), and cytoplasm (UPR ) through distinct mechanisms. While previous studies have shown that the UPRs are intuitively linked to organismal aging, a systematic assay on the temporal regulation of different type of UPRs during aging is still lacking. Here, using Caenorhabditis elegans (C. elegans) as the model system, we found that the endogenous UPRs (UPR , UPR , and UPR ) elevate with age, but their inducibility exhibits an age-dependent decline. Moreover, we revealed that the temporal requirements to induce different types of UPRs are distinct. Namely, while the UPR can only be induced during the larval stage, the UPR can be induced until early adulthood and the inducibility of UPR is well maintained until mid-late stage of life. Furthermore, we showed that different tissues may exhibit distinct temporal profiles of UPR inducibility during aging. Collectively, our findings demonstrate that UPRs of different subcellular compartments may have distinct temporal mechanisms during aging.
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http://dx.doi.org/10.1002/jcp.30215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026671PMC
July 2021