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1.
Front Cell Infect Microbiol ; 11: 643913, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816348

RESUMO

Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality worldwide, and inflammatory damage induced by bacterial infections is an important contributor to the etiology of COPD. Fusobacterium nucleatum, a recognized periodontal pathogen, is considered as a biomarker of lung function deterioration of COPD patients coinfected with Pseudomonas aerugionsa, but the underlying mechanism is still unclear. This study established single- and dual-species infection models, bacterial simultaneous and sequential infection models, and found that F. nucleatum could coaggregate with P. aeruginosa to synergistically invade into pulmonary epithelial cells and transiently resist P. aeruginosa-induced cytotoxic damage to amplify IL-6 and TNF-α associated inflammation in pulmonary epithelial cells simultaneously infected with P. aeruginosa and F. nucleatum. Furthermore, F. nucleatum pretreatment or subsequential infection could maintain or even aggravate P. aeruginosa-induced inflammatory cytotoxicity of pulmonary epithelial cells. These results indicate that oral pathogen F. nucleatum coaggregates with P. aeruginosa to facilitate bacterial invasion and modulates the inflammatory cytotoxicity of pulmonary epithelial cells, which may contribute to lung function deterioration of COPD patients accompanied with P. aeruginosa and F. nucleatum coinfection.

2.
Acta Biomater ; 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33831575

RESUMO

The effect of the second phase on the mechanical properties and corrosion resistance of Mg alloys has been systematically studied. However, there is limited information on the effect of the second phase on protein adsorption behavior. In the present study, the effect of the second phase on protein adsorption on the surfaces of biodegradable Mg alloys was investigated using experimental methods and molecular dynamics (MD) simulations. The experimental results showed that the effect of the second phase on fibrinogen adsorption was type-dependent. Fibrinogen preferentially adsorbed on Y-, Ce-, or Nd-involved second phases, while the second phase containing Zn inhibited its adsorption. MD simulations revealed the mechanism of the second phase that influenced protein adsorption in terms of charge distribution, surface-protein interaction energy, and water molecule distribution. Our studies proposed a deep understanding of the design of Mg-based biomaterials with superior biocompatibility. STATEMENT OF SIGNIFICANCE: : Mechanical properties, uniform degradation, and biocompatibility must be considered while designing biomedical Mg alloys. To improve the mechanical properties and corrosion resistance of Mg alloys, the second phase is usually required. However, the effects of the second phase on biocompatibility of Mg alloys have been rarely reported. Here, the influence of the second phase on protein adsorption was experimentally studied by designing Mg alloys with different types of second phase. The first principle calculation and MD simulation were used to reveal the mechanism by which the second phase influences protein adsorption. This work could be used to better elucidate the protein adsorption mechanisms and design principles to improve the biocompatibility of Mg alloys.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33646449

RESUMO

In China, there is a high prevalence of antibiotic-resistant Helicobacter pylori infections in the population. The aim of the study was to assess a new ARMS-PCR test for detection of H. pylori clarithromycin resistance (CR) and quinolone resistance (QR) mutations and evaluate the spectrum of antibiotic resistance in patients from three Chinese provinces. Sanger sequencing and multiplex ARMS-PCR were used to detect H. pylori CR and QR bacteria in gastric biopsy samples. Among the 1,182 patients enrolled with gastritis, 643 (54.4%) were positive for H. pylori. Of these, 371 (57.7%) had antibiotic-resistant strains, comprising 236 (63.6%) with a single drug antibiotic-resistant strain and 135 (36.4%) with multiple drug-resistant strains. Following Sanger sequencing analysis of 23S rRNA and gyrA gene for mutations (antibiotic resistance markers), rates of CR, QR, and multidrug resistance (CR and QR) were 19.9, 12.0, and 25.8%, respectively. The 23S rRNA CR mutation A2143G (286, 96.9%) and the gyrA QR mutations C261A (85, 31.5%) and G271A (71, 26.3%) were common. Benchmarking against Sanger sequencing results, multiplex ARMS-PCR test had a high diagnostic sensitivity and specificity for detection of CR (96 and 93%), QR (95 and 92%) and multidrug resistance (95 and 95%). Based on our findings, the high incidence of single and multiple antibiotic resistance requires the routine checking of antibiotic resistance in all patients with suspected H. pylori infections. Multiplex ARMS-PCR is a simple and rapid test that can be now used for more efficient treatment of H. pylori infections and reduces the misuse of antibiotics.

4.
Biotechnol Lett ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646457

RESUMO

Cytidine is an important raw material for nucleic acid health food and genetic engineering research. In recent years, it has shown irreplaceable effects in anti-virus, anti-tumor, and AIDS drugs. Its biosynthetic pathway is complex and highly regulated. In this study, overexpression of uracil permease and a nucleoside transporter from Bacillus amyloliquefaciens related to cell membrane transport in Escherichia coli strain BG-08 was found to increase cytidine production in shake flask cultivation by 1.3-fold (0.91 ± 0.03 g/L) and 1.8-fold (1.26 ± 0.03 g/L) relative to that of the original strain (0.70 ± 0.03 g/L), respectively. Co-overexpression of uracil permease and a nucleoside transporter further increased cytidine yield by 2.7-fold (1.59 ± 0.05 g/L) compared with that of the original strain. These results indicate that the overexpressed uracil permease and nucleoside transporter can promote the accumulation of cytidine, and the two proteins play a synergistic role in the secretion of cytidine in Escherichia coli.

5.
J Int Med Res ; 49(3): 300060521999768, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33752447

RESUMO

OBJECTIVE: To assess safety and efficacy of a novel intubation laryngeal mask airway (ILMA) during the recovery period following supratentorial tumour surgery. METHODS: Patients who underwent supratentorial tumour surgery at our centre from January 2012 to December 2016 were eligible for this prospective randomised, parallel group study. We developed a novel ILMA using closely fitting laryngeal masks (No. 4/5) with 7.0/7.5 mm endotracheal tubes (ETT) plus screw fixators and anti-pollution sleeves. RESULTS: In total, 100 patients were intubated with the novel ILMA and 100 the ETT. There were no differences between groups in haemodynamic variables, oxygen saturation, exhaled CO2, or bispectral index all recorded during the 72-hour recovery period. However, there were significantly fewer incidences of coughing, less fluid drainage and lower haemoglobin levels in surgical fluid in the ILMA group compared with the ETT group. CONCLUSION: Our novel ILMA device was associated with reduced coughing, fluid drainage and blood in surgical drain during the recovery period following supratentorial tumour surgery.

6.
Sci Adv ; 7(11)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33712456

RESUMO

Traumatic brain injury (TBI) leads to high mortality rate. We aimed to identify the key cytokines favoring TBI repair and found that patients with TBI with a better outcome robustly increased concentrations of macrophage colony-stimulating factor, interleukin-6, and transforming growth factor-ß (termed M6T) in cerebrospinal fluid or plasma. Using TBI mice, we identified that M2-like macrophage, microglia, and endothelial cell were major sources to produce M6T. Together with the in vivo tracking of mCherry+ macrophages in zebrafish models, we confirmed that M6T treatment accelerated blood-borne macrophage infiltration and polarization toward a subset of tissue repair macrophages that expressed similar genes as microglia for neuroprotection, angiogenesis and cell migration. M6T therapy in TBI mice and zebrafish improved neurological function while blocking M6T-exacerbated brain injury. Considering low concentrations of M6T in some patients with poor prognostic, M6T treatment might repair TBI via generating a previously unidentified subset of tissue repair macrophages.

7.
J Org Chem ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33764062

RESUMO

A catalyst-free and transition-metal-free method for the synthesis of 1,2-diketones from aerobic alkyne oxidation was reported. The oxidation of various internal alkynes, especially more challenging aryl-alkyl acetylenes, proceeded smoothly with inexpensive, easily handled, and commercially available potassium persulfate and an ambient air balloon, achieving the corresponding 1,2-diketones with up to 85% yields. Meanwhile, mechanistic studies indicated a radical process, and the two oxygen atoms in the 1,2-diketons were most likely from persulfate salts and molecular oxygen, respectively, rather than water.

8.
Nucleic Acids Res ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33721016

RESUMO

The compact CRISPR/Cas9 system, which can be delivered with their gRNA and a full-length promoter for expression by a single adeno-associated virus (AAV), is a promising platform for therapeutic applications. We previously identified a compact SauriCas9 that displays high activity and requires a simple NNGG PAM, but the specificity is moderate. Here, we identified three compact Cas9 orthologs, Staphylococcus lugdunensis Cas9 (SlugCas9), Staphylococcus lutrae Cas9 (SlutrCas9) and Staphylococcus haemolyticus Cas9 (ShaCas9), for mammalian genome editing. Of these three Cas9 orthologs, SlugCas9 recognizes a simple NNGG PAM and displays comparable activity to SaCas9. Importantly, we generated a SlugCas9-SaCas9 chimeric nuclease, which has both high specificity and high activity. We finally engineered SlugCas9 with mutations to generate a high-fidelity variant that maintains high specificity without compromising on-target editing efficiency. Our study offers important minimal Cas9 tools that are ideal for both basic research and clinical applications.

9.
Infect Immun ; 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33722928

RESUMO

H9N2 avian influenza virus has been continuously circulating among poultry and could infect mammals, indicating that this virus is a potential pandemic strain. During influenza pandemics, secondary bacterial (particularly pneumococcal) pneumonia usually contributes to excess mortality. In the present study, we observed the dynamic effect of H9N2 virus infection on host defense against secondary pneumococcal infection in mice. BALB/c mice were intranasally inoculated with 1.2 × 105 plaque forming units (PFU) of H9N2 virus followed by 1 × 106 colony forming units of Streptococcus pneumoniae on 7, 14 or 28 days post-H9N2 infection (D.P.I.). The bacterial load, histopathology, body weight and survival were assessed after pneumococcal infection. Our results showed that H9N2 virus infection had no significant impact on host resistance to secondary pneumococcal infection on 7 D.P.I. However, H9N2 virus infection increased pulmonary pneumococcal clearance and reduced pneumococcal pneumonia-induced morbidity after secondary pneumococcal infection on 14 or 28 D.P.I., as reflected by significantly decreased bacterial loads, markedly alleviated pulmonary histopathological changes and significantly reduced weight loss in mice infected with H9N2 virus followed by S. pneumoniae compared with mice infected only with S. pneumoniae Further, the significantly decreased bacterial loads were observed when mice were previously infected with a higher dose (1.2 × 106 PFU) of H9N2 virus. Besides, similar to the results obtained in BALB/c mice, improvement in pulmonary pneumococcal clearance was also observed in C57BL/6 mice. Overall, our results showed that pulmonary pneumococcal clearance is improved after resolution of H9N2 virus infection in mice.

10.
BMC Psychiatry ; 21(1): 152, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726704

RESUMO

INTRODUCTION: To explore the prevalence of depressive symptoms and the associated risk factors in frontline nurses under COVID-19 pandemic. METHODS: This cross-sectional study was conducted from February 20, 2020 to March 20, 2020 and involved 562 frontline nurses. The effective response rate was 87.68%. After propensity score matched, there were 498 participants left. Extensive characteristics, including demographics, dietary habits, life-related factors, work-related factors, and psychological factors were collected based on a self-reported questionnaire. Specific scales measured the levels of sleep quality, physical activity, depressive symptoms, perceived organization support and psychological capital. Adjusted odds ratios and 95% confidence intervals were determined by binary paired logistic regression. RESULTS: Of the nurses enrolled in the study, 50.90% had depressive symptoms. Three independent risk factors were identified: poor sleep quality (OR = 1.608, 95% CI: 1.384-1.896), lower optimism of psychological capital (OR = 0.879, 95% CI: 0.805-0.960) and no visiting friend constantly (OR = 0.513, 95% CI: 0.286-0.920). CONCLUSIONS: This study revealed a considerable high prevalence of depressive symptoms in frontline nurses during the COVID-19 outbreak, and identified three risk factors, which were poor sleep quality, lower optimism of psychological capital, and no visiting friend constantly. Protecting mental health of nurses is important for COVID-19 pandemic control and their wellbeing. These findings enrich the existing theoretical model of depression and demonstrated a critical need for additional strategies that could address the mental health in frontline nurses for policymakers.


Assuntos
Pandemias , Ansiedade , Estudos Transversais , Depressão/epidemiologia , Humanos , Prevalência , Pontuação de Propensão , Fatores de Risco
11.
Traffic Inj Prev ; : 1-6, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33739223

RESUMO

OBJECTIVE: Driver posture monitoring is useful for evaluating the readiness to take over from highly automated driving systems as well as for designing intelligent restraint systems to reduce injury. The aim of this study was to develop a real-time and robust driver posture monitoring system using pressure measurement. METHODS: Driver motion and pressure measurement were collected from 23 differently sized participants performing 42 driving and non-driving activities. Nine typical driver postures were identified by analyzing trunk and feet positions in 3 D space for classification. One deep learning classifier and two Random Forest classifiers were trained respectively on pressure distribution, absolute and relative pressure features extracted from pressure measurement. Leave-One-Out cross-validation was performed to evaluate the performance of the classifiers. RESULTS: Without considering feet positions, all the classifiers could provide reliable recognition of the normal trunk position for standard driving with an accuracy around 98%. With help of a reference sitting position, the best performance was achieved by Random Forest classifier trained on the relative pressure features with an average classification accuracy of 80.5% across 9 typical postures and 23 drivers. The main errors were related to the recognition of feet positions when applying braking and relaxing both feet on the floor. CONCLUSIONS: Pressure measurement could be a good alternative or complementary to camera based driver postural monitoring system. Results show that all classifiers proposed in the work could predict the trunk position for standard driving. With help of an initial posture, Random Forest classifier with relative pressure features could classify trunk positions with high accuracy. However, further effort is needed to improve the accuracy of feet position prediction especially by adding more foot related task data.

12.
Gerontology ; : 1-10, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33657570

RESUMO

AIMS: Using specials wearable sensors, we explored changes in gait and balance parameters, over time, in elderly patients at high risk of diabetic foot, wearing different types of footwear. This assessed the relationship between gait and balance changes in elderly diabetic patients and the development of foot ulcers, in a bid to uncover potential benefits of wearable devices in the prognosis and management of the aforementioned complication. METHODS: A wearable sensor-based monitoring system was used in middle-elderly patients with diabetes who recently recovered from neuropathic plantar foot ulcers. A total of 6 patients (age range: 55-80 years) were divided into 2 groups: the therapeutic footwear group (n = 3) and the regular footwear (n = 3) group. All subjects were assessed for gait and balance throughout the study period. Walking ability and gait pattern were assessed by allowing participants to walk normally for 1 min at habitual speed. The balance assessment program incorporated the "feet together" standing test and the instrumented modified Clinical Test of Sensory Integration and Balance. Biomechanical information was monitored at least 3 times. RESULTS: We found significant differences in stride length (p < 0.0001), stride velocity (p < 0.0001), and double support (p < 0.0001) between the offloading footwear group (OG) and the regular footwear group on a group × time interaction. The balance test embracing eyes-open condition revealed a significant difference in Hip Sway (p = 0.004), COM Range ML (p = 0.008), and COM Position (p = 0.004) between the 2 groups. Longitudinally, the offloading group exhibited slight improvement in the performance of gait parameters over time. The stride length (odds ratio 3.54, 95% CI 1.34-9.34, p = 0.018) and velocity (odds ratio 3.13, 95% CI 1.19-8.19, p = 0.033) of OG patients increased, converse to the double-support period (odds ratio 6.20, 95% CI 1.97-19.55, p = 0.002), which decreased. CONCLUSIONS: Special wearable devices can accurately monitor gait and balance parameters in patients in real time. The finding reveals the feasibility and effectiveness of advanced wearable sensors in the prevention and management of diabetic foot ulcer and provides a solid background for future research. In addition, the development of foot ulcers in elderly diabetic patients may be associated with changes in gait parameters and the nature of footwear. Even so, larger follow-up studies are needed to validate our findings.

13.
EMBO Rep ; 22(4): e50994, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33565211

RESUMO

The ability of neural stem cells (NSCs) to switch between quiescence and proliferation is crucial for brain development and homeostasis. Increasing evidence suggests that variants of histone lysine methyltransferases including KMT5A are associated with neurodevelopmental disorders. However, the function of KMT5A/Pr-set7/SETD8 in the central nervous system is not well established. Here, we show that Drosophila Pr-Set7 is a novel regulator of NSC reactivation. Loss of function of pr-set7 causes a delay in NSC reactivation and loss of H4K20 monomethylation in the brain. Through NSC-specific in vivo profiling, we demonstrate that Pr-set7 binds to the promoter region of cyclin-dependent kinase 1 (cdk1) and Wnt pathway transcriptional co-activator earthbound1/jerky (ebd1). Further validation indicates that Pr-set7 is required for the expression of cdk1 and ebd1 in the brain. Similar to Pr-set7, Cdk1 and Ebd1 promote NSC reactivation. Finally, overexpression of Cdk1 and Ebd1 significantly suppressed NSC reactivation defects observed in pr-set7-depleted brains. Therefore, Pr-set7 promotes NSC reactivation by regulating Wnt signaling and cell cycle progression. Our findings may contribute to the understanding of mammalian KMT5A/PR-SET7/SETD8 during brain development.

15.
Oxid Med Cell Longev ; 2021: 6610124, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33603948

RESUMO

Nonalcoholic fatty liver disease is the most common liver disease worldwide. Hepatic steatosis and oxidative stress are the main characteristics of NAFLD (nonalcoholic fatty liver disease), which also affect its prognosis. Bixin acts as novel Nrf2 (NF-E2 p45-related factor 2) activator with the cytoprotection against oxidative stress and inflammation; this study mainly focused on the mechanism of Nrf2 activation by bixin and explored its potential feasibilities in long-term high-fat diet- (HFD-) caused hepatic steatosis and inflammatory response in vitro and in vivo. Bixin was found to activate Nrf2 signals by the modification of critical Keap1 (Kelch-like ECH-associated protein 1) cystine and competitive interaction with Keap1 with upregulating P62 mRNA and protein expression. In human liver cells exposed to FFA (free fatty acid), bixin displayed a pronounced cytoprotective activity with upregulation of Nrf2-mediated gene expression, such as PPARα and its targets related with fatty acid oxidation. In HFD-fed mice, systemic administration of bixin attenuated lipid accumulation, decreased oxidant inflammatory damage in the liver, and reduced circulating lipid levels through Nrf2. Different from most of other established inducers, bixin activated Nrf2 signals through two different mechanisms with safe administration for protection of oxidant inflammatory damage and attenuation of lipid accumulation in the in vivo long-term HFD-fed mice. Bixin represents a prototype Nrf2 activator that displays cytoprotective activity upon system administration targeting hepatic steatosis and oxidant inflammation originating from long-term HFD-fed mice. And bixin-based Nrf2-directed systemic intervention may also provide therapeutic benefit in protecting other organs in the process of metabolic syndrome.

16.
G3 (Bethesda) ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33617633

RESUMO

Plant long non-coding RNAs (lncRNAs) function in diverse biological processes, and lncRNA expression is under epigenetic regulation, including by cytosine DNA methylation. However, it remains unclear whether 5-methylcytosine (5mC) play a similar role in different sequence contexts (CG, CHG, and CHH). In this study, we characterized and compared the profiles of genome-wide lncRNA profiles (including long intergenic non-coding RNAs [lincRNAs] and long noncoding natural antisense transcripts [lncNATs]) of a null mutant of the rice DNA methyltransferase 1, OsMET1-2 (designated OsMET1-2-/-) and its isogenic wild type (OsMET1-2+/+). The En/Spm transposable element (TE) family, which was heavily methylated in OsMET1-2+/+, was transcriptionally de-repressed in OsMET1-2-/- due to genome-wide erasure of CG methylation, and this led to abundant production of specific lncRNAs. In addition, RdDM-mediated CHH hypermethylation was increased in the 5'-upstream genomic regions of lncRNAs in OsMET1-2-/-. The positive correlation between the expression of lincRNAs and that of their proximal protein-coding genes was also analyzed. Our study shows that CG methylation negatively regulates the TE-related expression of lncRNA and demonstrates that CHH methylation is also involved in the regulation of lncRNA expression.

17.
Medicine (Baltimore) ; 100(3): e23918, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33545962

RESUMO

BACKGROUND: Obesity is an independent risk factor for the occurrence and development of diabetes. Patients with diabetes combined with obesity will face serious burdens such as increase in insulin resistance and difficulty in blood glucose control. As a safe, effective, economical, and simple intervention, Tuina is more acceptable to the public than drugs. The objective of this systematic evaluation and meta-analysis is to evaluate the efficacy and safety of Tuina for diabetes with obesity. METHODS: We will search the following electronic databases: PubMed, Embase, Cochrane Library, Web of science, Chinese National Knowledge Infrastructure (CNKI), Sino Med, Wanfang, Chinese Clinical Trial Registry System, China Biomedical Literature Database (CBM). The time limit for retrieving studies is from establishment to November 2020 for each database. Randomized controlled clinical trials related to Tuina intervention on diabetes with obesity will be included. Data synthesis, sensitivity analysis, subgroup analysis as well as the assessment of bias risk will be conducted by using Stata V.13.0 and Review manager 5.3 software. RESULTS: This study will provide a quantitative and standardized evaluation for the efficacy of Tuina therapy on diabetes with obesity. CONCLUSION: This systematic review and meta-analysis will provide the high-quality evidence of whether Tuina is an effective intervention for diabetes with obesity. REGISTRATION NUMBER: INPLASY2020110106.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Obesidade Mórbida , Diabetes Mellitus Tipo 2/complicações , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisões Sistemáticas como Assunto , Resultado do Tratamento
18.
Cells ; 10(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466414

RESUMO

Parkinson's disease (PD) is an age-dependent neurodegenerative condition. Leucine-rich repeat kinase 2 (LRRK2) mutations are the most frequent cause of sporadic and autosomal dominant PD. The exact role of LRRK2 protective variants (R1398H, N551K) together with a pathogenic mutant (G2019S) in aging and neurodegeneration is unknown. We generated the following myc-tagged UAS-LRRK2 transgenic Drosophila: LRRK2 (WT), N551K, R1398H, G2019S single allele, and double-mutants (N551K/G2019S or R1398H/G2019S). The protective variants alone were able to suppress the phenotypic effects caused by the pathogenic LRRK2 mutation. Next, we conducted RNA-sequencing using mRNA isolated from dopaminergic neurons of these different groups of transgenic Drosophila. Using pathway enrichment analysis, we identified the top 10 modules (p < 0.05), with "LRRK2 in neurons in Parkinson's disease" among the candidates. Further dissection of this pathway identified the most significantly modulated gene nodes such as eEF1A2, ACTB, eEF1A, and actin cytoskeleton reorganization. The induction of the pathway was successfully restored by the R1398H protective variant and R1398H-G2019S or N551K-G2019S rescue experiments. The oxidoreductase family of genes was also active in the pathogenic mutant and restored in protective and rescue variants. In summary, we provide in vivo evidence supporting the neuroprotective effects of LRRK2 variants. RNA sequencing of dopaminergic neurons identified upregulation of specific gene pathways in the Drosophila carrying the pathogenic variant, and this was restored in the rescue phenotypes. Using protective gene variants, our study identifies potential new targets and provides proof of principle of a new therapeutic approach that will further our understanding of aging and neurodegeneration in PD.

19.
Chem Soc Rev ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33475099

RESUMO

Porphyrin-based frameworks, as specific kinds of metal-organic frameworks (MOFs) and covalent organic frameworks (COFs), have been widely used in energy-related conversion processes, including the oxygen reduction reaction (ORR), oxygen evolution reaction (OER) and CO2 reduction reaction (CO2RR), and also in energy-related storage technologies such as rechargeable Zn-air batteries. This review starts by summarizing typical crystal structures, molecular building blocks, and common synthetic procedures of various porphyrin-based frameworks used in energy-related technologies. Then, a brief introduction is provided and representative applications of porphyrin-based frameworks in ORR, OER, Zn-air batteries, and CO2RR are discussed. The performance comparison of these porphyrin-based frameworks in each field is also summarized and discussed, which pinpoints a clear structure-activity relationship. In addition to utilizing highly active porphyrin units for catalytic conversions, regulating the porous structures of porphyrin-based frameworks will enhance mass transfer and growing porphyrin-based frameworks on conductive supports will accelerate electron transfer, which will result in the improvement of the electrocatalytic performance. This review is therefore valuable for the rational design of more efficient porphyrin-based framework catalytic systems in energy-related conversion and storage technologies.

20.
Theranostics ; 11(1): 14-26, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391458

RESUMO

Rationale: Liver fibrosis is frequently associated with gut barrier dysfunction, and the lipopolysaccharides (LPS) -TLR4 pathway is common to the development of both. Intestinal alkaline phosphatase (IAP) has the ability to detoxify LPS, as well as maintain intestinal tight junction proteins and gut barrier integrity. Therefore, we hypothesized that IAP may function as a novel therapy to prevent liver fibrosis. Methods: Stool IAP activity from cirrhotic patients were determined. Common bile duct ligation (CBDL) and Carbon Tetrachloride-4 (CCl4)-induced liver fibrosis models were used in WT, IAP knockout (KO), and TLR4 KO mice supplemented with or without exogenous IAP in their drinking water. The gut barrier function and liver fibrosis markers were tested. Results: Human stool IAP activity was decreased in the setting of liver cirrhosis. In mice, IAP activity and genes expression decreased after CBDL and CCl4 exposure. Intestinal tight junction related genes and gut barrier function were impaired in both models of liver fibrosis. Oral IAP supplementation attenuated the decrease in small intestine tight junction protein gene expression and gut barrier function. Liver fibrosis markers were significantly higher in IAP KO compared to WT mice in both models, while oral IAP rescued liver fibrosis in both WT and IAP KO mice. In contrast, IAP supplementation did not attenuate fibrosis in TLR4 KO mice in either model. Conclusions: Endogenous IAP is decreased during liver fibrosis, perhaps contributing to the gut barrier dysfunction and worsening fibrosis. Oral IAP protects the gut barrier and further prevents the development of liver fibrosis via a TLR4-mediated mechanism.

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