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1.
Commun Biol ; 5(1): 32, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017648

RESUMO

As a master regulator of the balance between NO signaling and protein S-nitrosylation, S-nitrosoglutathione (GSNO) reductase (GSNOR) is involved in various developmental processes and stress responses. However, the proteins and specific sites that can be S-nitrosylated, especially in microorganisms, and the physiological functions of S-nitrosylated proteins remain unclear. Herein, we show that the ganoderic acid (GA) content in GSNOR-silenced (GSNORi) strains is significantly lower (by 25%) than in wild type (WT) under heat stress (HS). Additionally, silencing GSNOR results in an 80% increase in catalase (CAT) activity, which consequently decreases GA accumulation via inhibition of ROS signaling. The mechanism of GSNOR-mediated control of CAT activity may be via protein S-nitrosylation. In support of this possibility, we show that CAT is S-nitrosylated (as shown via recombinant protein in vitro and via GSNORi strains in vivo). Additionally, Cys (cysteine) 401, Cys642 and Cys653 in CAT are S-nitrosylation sites (assayed via mass spectrometry analysis), and Cys401 may play a pivotal role in CAT activity. These findings indicate a mechanism by which GSNOR responds to stress and regulates secondary metabolite content through protein S-nitrosylation. Our results also define a new S-nitrosylation site and the function of an S-nitrosylated protein regulated by GSNOR in microorganisms.

2.
Anal Chem ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35018772

RESUMO

Biomimetic DNA walking machines have gained great success in scrutinizing the microscopic world and sensitive biosensing of disease biomarkers. Despite superb achievements, the research on DNA walking machines for simultaneous detection of multiple analytes is still rare, while the design and realization of multiplexing are considered as an important bottleneck. The multiplex detection of biomarkers can not only improve the specificity of bioassays but also avoid the squander of valuable biological specimens. Herein, we reported multiplex three-dimensional (3D) DNA walking machines based on high-resolution inductively coupled plasma mass spectrometry (HR-ICPMS) for lung cancer-associated miRNA detection. In the presence of lung cancer-associated target miRNAs (miR-21, miR-141, and miR-125b), DNA walking machines were stimulated and operated to liberate a large number of lanthanide elements (Tb, Ho, and Tm), and then the signals were collected simultaneously by HR-ICPMS. The recovery test of target miRNAs in human serum and the simultaneous monitoring experiment of three miRNAs in human lung cancer cell line (A549) and normal cell line (HBE) specimens display satisfactory analysis capabilities for complex biological samples. Thanks to the vast potential of lanthanide tags and the modular design, the proposed bioassay might flexibly detect different miRNA combinations with corresponding sets of DNA walking machines to meet the requirements of various tasks.

5.
ACS Biomater Sci Eng ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34984904

RESUMO

Subperiosteal implants represent an alternative implant approach for cases with severe bone atrophy. Although some successful clinical cases have been reported, the biomechanical stability of subperiosteal implants remains unclear, and more data are needed to confirm the feasibility of this approach. Therefore, this study investigated the biomechanical characteristics of subperiosteal implants based on histological observation, clinical cases, and finite element analysis. Finite element analysis indicated that subperiosteal implants with a lattice-like structure could better disperse the stress to the underlying bone surface. A novel customized subperiosteal implant was then digitally designed and fabricated using an additive manufacturing technology. Six beagle dogs received such customized subperiosteal implants. Histological and microcomputed tomography examination showed new bone growth into and around the implant. Patient-specific subperiosteal implants were placed into the edentulous mandibular bone, with immediate loading. The implant was functional, without pain or infection, over a 12 month observation period. Images taken 12 months post-operatively showed new bone formation and osseointegration of the device. This indicated that 3D-printed lattice-like subperiosteal implants have sufficient stability for the rehabilitation of severely atrophic ridges.

6.
Nanoscale ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34985067

RESUMO

Monitoring the expression level of the intracellular tumor suppressor gene p21 mRNA is essential to reveal the progress and prognosis of a tumor. Methods widely reported for the detection of p21 mRNA are the real-time polymerase chain reaction and Northern blot. However, these methods only detect mRNA in vitro and cannot realize the in situ monitoring of the p21 mRNA expression level in living cells. Additionally, the sensor for the real-time tracking and monitoring of the p21 mRNA location without the help of a transfection reagent in living cells is still limited. Herein, a novel sticky-flare was constructed for the dynamic monitoring of the temporal and spatial variations of p21 mRNA in living cells. The nanoprobe consists of AuNP, a recognition sequence modified with Cy5, and a thiol-modified DNA sequence. The thiol oligonucleotide strand could act partially complementary to the Cy5-modified oligonucleotide strand to form a double-stranded DNA linked to AuNP, resulting in the fluorescence quenching of Cy5 due to the energy transfer from Cy5 to the gold sphere. In the presence of p21 mRNA, the Cy5-modified recognition nucleic acid specifically bound to p21 mRNA to form a more stable double chain and escaped from the gold sphere, leading to the recovery of red fluorescence. Our method is better than other methods in its ability to quantify the spatial distribution and expression level of p21 mRNA in living cells and discriminate various tumor cell lines with different p21 mRNA expression levels by the naked eye. Particularly, the sticky-flare probe used in this assay could allow the visual evaluation of the tumor treatment effect and the determination of the tumor progression stage by enabling monitoring of the relative expression level of p21 mRNA in tumor cells after cisplatin treatment. The method reported here is accurate, reliable and needs no auxiliary tools (transfection reagent), and thereby provides a promising route for the prognostic evaluation and drug development of cancer treatment in the future.

7.
J Hazard Mater ; 427: 128204, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-35007804

RESUMO

Metal leaching and catalytic stability are the key issues in Fenton-like reaction. Herein, a hollow yolk-shell nanoreactor (HYSCN) with shell confined Co species was fabricated for peroxymonosulfate (PMS) activation to degrade carbamazepine (CBZ). The uniform Co nanoparticles were completely anchored in a hollow void, further confined by a porous N-doped carbon shell. The unique construction significantly reduces Co species leaching in PMS activation and enhances catalytic stability. Co leaching came from HYSCN dropped by almost fourfold compared to CN-8 without shell confined (0.403 mg/L to 0.120 mg/L). The catalytic stability is also greatly improved, confirming the dominant role of heterogeneous catalysis in the HYSCN/PMS system. HYSCN exhibits excellent catalytic performance compared to a solid structure (SCSCN), demonstrating the significance of hollow structures. Mechanism study found that HO•, SO4•- and 1O2 induced in HYSCN/PMS system and the relative contributions were distinguished and quantified by stoichiometric methods. The UPLC-Q-TOF-MS/MS was used to identify the CBZ degraded intermediate products and the possible degradation pathway was proposed. This study will provide theoretical guidance for reducing metal leaching and improving catalytic stability in the PMS activation.

8.
Food Chem ; 378: 132089, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35032798

RESUMO

Collagen from tilapia skin was extracted and confirmed as type I collagen. Collagen was then hydrolyzed with alcalase for 4 h and the released peptides were identified. The structure-activity relationship of collagen-released peptides showed that proline at position C3 played a key role in improving ACE inhibitory activity, while proline at position C2 had a negative effect. Collagen peptide release kinetics showed that with the extension of time, the number of peptides increased dramatically at first, decreased, and then tended to be stable. This indicated that collagen peptides mainly originated from primary enzymolysis at the first stage and began to undergo secondary hydrolysis in the second stage. Afterwards, secondary enzymolysis was dominant at the third stage and finally remained stable at final two stages. Understanding the pattern of collagen peptide release kinetics might offer a powerful approach in the collagen-peptide food processing industry to better control food safety and quality.

10.
Adv Sci (Weinh) ; : e2103697, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35038246

RESUMO

Few intravenously administered mesenchymal stromal cells (MSCs) engraft to the injured myocardium, thereby limiting their therapeutic efficacy for the treatment of ischemic heart injury. Here, it is found that irisin pretreatment increases the cardiac homing of adipose tissue-derived MSCs (ADSCs) administered by single and multiple intravenous injections to mice with MI/R by more than fivefold, which subsequently increases their antiapoptotic, proangiogenic, and antifibrotic effects in rats and mice that underwent MI/R. RNA sequencing, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis, and loss-of-function studies identified CSF2RB as a cytokine receptor that facilitates the chemotaxis of irisin-treated ADSCs in the presence of CSF2, a chemokine that is significantly upregulated in the ischemic heart. Cardiac-specific CSF2 knockdown blocked the cardiac homing and cardioprotection abilities of intravenously injected irisin-treated ADSCs in mice subjected to MI/R. Moreover, irisin pretreatment reduced the apoptosis of hydrogen peroxide-induced ADSCs and increased the paracrine proangiogenic effect of ADSCs. ERK1/2-SOD2, and ERK1/2-ANGPTL4 are responsible for the antiapoptotic and paracrine angiogenic effects of irisin-treated ADSCs, respectively. Integrin αV/ß5 is identified as the irisin receptor in ADSCs. These results provide compelling evidence that irisin pretreatment can be an effective means to optimize intravenously delivered MSCs as therapy for ischemic heart injury.

11.
J Affect Disord ; 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34995705

RESUMO

BACKGROUND: This study examined the extent to which the network structure of anxiety and depression among adolescents identified during the peak of the COVID-19 pandemic could be cross-validated in a sample of adolescents assessed after the COVID-19 peak. METHODS: Two cross-sectional surveys were conducted between February 20 and 27, 2020 and between April 11 and 19, 2020, respectively. Depressive and anxiety symptoms were assessed using 20-item the Center for Epidemiological Studies-Depression and 7-item Generalized Anxiety Disorder, respectively. Anxiety-depression networks of the first and second assessments were estimated separately using a sparse Graphical Gaussian Model combined with the graphical least absolute shrinkage and selection operator method. A Network Comparison Test was conducted to assess differences between the two networks. RESULTS: The most central symptoms in the first and second survey networks were Depressed affect and Nervousness. Compared with connections in the first survey network, connections in the second survey network analysis between Relax- Nervousness-Depressive affect-Interpersonal problems (diff, contrast: second survey-first survey. diff=-0.04, P=0.04; diff=-0.03, P=0.03; diff=-0.03, P=0.04), and Irritability-Somatic complaints (diff=-0.04, P=0.02) were weaker while connections of Somatic complaints-Nervousness (diff=0.05, P<0.001), Somatic complaints-Depressive affect (diff=0.03, P=0.009), and Irritability-Control worry-Restlessness (diff=0.02, P=0.03; diff=0.05, P=0.02) were stronger. CONCLUSIONS: Depressed affect emerged as a robust central symptom and bridge symptom across Anxiety-Depression networks. Considering the negative impact of depression and anxiety on daily life, timely interventions targeting depressed affect should be implemented to reduce the co-occurrence of anxious and depressed symptoms among adolescents during the COVID-19 pandemic.

12.
Mol Ther Nucleic Acids ; 27: 256-275, 2022 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-35024240

RESUMO

Existing studies have revealed that microRNAs (miRNAs) have a role in cognitive deficits in Alzheimer's disease (AD). However, the function and pathophysiological mechanism of deregulated miRNAs underlying AD pathology remain to be investigated. The present study aimed to clarify the role and mechanism of miR-148a-3p in AD. RNA sequencing, qRT-PCR, and western blot analysis were used to identify the aberrant expression and signaling of miR-148a-3p within cells, mice, and patients with AD. Molecular biology techniques involving luciferase reporter assays, gene overexpression and silencing, chromatin immunoprecipitation, and adeno-associated virus-based miRNA overexpression were used to explore the biological function and mechanisms of miR-148a-3p. Downregulation of miR-148a-3p was identified in AD. Upregulation of miR-148a-3p was found to protect neuronal cells against Aß-associated tau hyperphosphorylation by directly targeting p35/CDK5 and PTEN/p38 mitogen-activated protein kinase (MAPK) pathways. A mutual regulatory link between miR-148a-3p and PTEN using a feedforward arrangement was confirmed via promotion of transcription and expression of miR-148a-3p by way of the PTEN/Akt/CREB pathway. Significantly, in vivo targeting of miR-148a-3p signaling ameliorated cognitive deficits by decreasing p35/PTEN-elicited tau hyperphosphorylation, accompanied by feedforward transduction of the PTEN/Akt/CREB pathway. In conclusion, the present study implicated the miR-148a-3p/p35/PTEN pathway as an essential contributor to tau hyperphosphorylation and feedforward regulation in AD.

14.
17.
J Integr Plant Biol ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35023269

RESUMO

The transcription factor CONSTANS (CO) integrates day-length information to induce the expression of florigen FLOWERING LOCUS T (FT) in Arabidopsis. We recently reported that the C-terminal CCT domain of CO forms a complex with NUCLEAR FACTOR-YB/YC to recognize multiple cis-elements in the FT promoter, and the N-terminal tandem B-box domains form a homomultimeric assembly. However, the mechanism and biological function of CO multimerization remained unclear. Here, we report that CO takes on a head-to-tail oligomeric configuration via its B-boxes to mediate FT activation in long days. The crystal structure of B-boxesCO reveals a closely connected tandem B-box fold forming a continuous head-to-tail assembly through unique CDHH zinc fingers. Mutating the key residues involved in CO oligomerization resulted in a non-functional CO, as evidenced by the inability to rescue co mutants. By contrast, a transgene encoding a human-p53-derived tetrameric peptide in place of the B-boxesCO rescued the co mutant, emphasizing the essential role of B-boxesCO -mediated oligomerization. Furthermore, we found that the four TGTG-bearing cis-elements in FT proximal promoter are required for FT activation in long days. Our results suggest that CO forms a multimer to bind to the four TGTG motifs in the FT promoter to mediate FT activation. This article is protected by copyright. All rights reserved.

18.
J Transl Med ; 20(1): 16, 2022 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-34991592

RESUMO

Multiple myeloma is characterized by osteolytic lesions caused by reduced bone formation and activated bone resorption. An important feature of myeloma is a failure of bone healing after successful treatment. In this work, clinical studies indicated a highly positive correlation between bone marrow bacteria abundance and bone lesion numbers of myeloma patients in complete remission. Coculture experiments demonstrated that marrow Escherichia coli (E. coli) promotes osteoclast differentiation and inhibits osteoblast differentiation. Mechanism studies showed that E. coli lipopolysaccharides (LPS) activated NF-κB p65 signaling and reduced phosphorylated smad1/5/9 binding ability with RUNX2 promoter, leading to decreased RUNX2 expression in osteoblast progenitors. Additionally, LPS enhanced phosphorylated NF-κB p65 binding ability with NFATc1 promoter, leading to increased NFATc1 expression in osteoclast progenitors. In vivo studies revealed E. coli contributes to osteolytic bone lesion, and elimination of E. coli infection assists healing of bone lesion in mouse model of myeloma in complete remission. These findings establish a heretofore unrecognized effect for E. coli in the genesis of myeloma bone disease and suggest a new treatment strategy.

19.
Sensors (Basel) ; 22(1)2022 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-35009872

RESUMO

With the rapid development of land mobile satellite (LMS) systems, large scale sensors and devices are willing to request wireless services, which is a challenge to the quality of service requirement and spectrum resources utilization on onboard LMS systems. Under this situation, the non-orthogonal multiple access (NOMA) is regarded as a promising technology for improving spectrum efficiency of LMS systems. In this paper, we analyze the ergodic capacity (EC) of NOMA-based multi-antenna LMS systems in the presence of imperfect limitations, i.e., channel estimation errors, imperfect successive interference cancellation, and co-channel interference. By considering multiple antennas at the satellite and terrestrial sensor users, the closed-form expression for EC of the NOMA-based LMS systems with imperfect limitations is obtained. Monte Carlo simulations are provided to verify theoretical results and reveal the influence of key parameters on system performance.

20.
BMC Neurol ; 22(1): 5, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979998

RESUMO

BACKGROUND: Sleep characteristics associated with dementia are poorly defined and whether their associations vary by demographics and APOE genotype among older adults are unclear. METHODS: This population-based cross-sectional study included 4742 participants (age ≥ 65 years, 57.1% women) living in rural China. Sleep parameters were measured using the self-rated questionnaires of the Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale. Global cognitive function was assessed with the Mini-Mental State Examination (MMSE). Dementia was diagnosed following the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria, and the National Institute on Aging-Alzheimer's Association criteria for Alzheimer's disease (AD). Data were analysed using multiple logistic and general linear regression models. RESULTS: Dementia was diagnosed in 173 participants (115 with AD). Multivariable-adjusted odds ratio (OR) of dementia was 1.71 (95%CI, 1.07-2.72) for sleep duration ≤4 h/night (vs. > 6-8 h/night), 0.76 (0.49-1.18) for > 4-6 h/night, 1.63 (1.05-2.55) for > 8 h/night, 1.11 (1.03-1.20) for lower sleep efficiency (per 10% decrease), and 1.85 (1.19-2.89) for excessive daytime sleepiness. Very short sleep duration (≤4 h/night), lower sleep efficiency, and excessive daytime sleepiness were significantly associated with being diagnosed with AD (multivariable-adjusted OR range = 1.12-2.07; p < 0.05). The associations of sleep problems with dementia and AD were evident mainly among young-old adults (65-74 years) or APOE ε4 carriers. Among dementia-free participants, these sleep characteristics were significantly associated with a lower MMSE score. CONCLUSIONS: Self-reported sleep problems in dementia are characterized by very short or long sleep duration, low sleep efficiency, and excessive daytime sleepiness, especially among young-old people and APOE ε4 carriers. TRIAL REGISTRATION: ChiCTR1800017758 (Aug 13, 2018).


Assuntos
Doença de Alzheimer , Demência/epidemiologia , Sono , Idoso , Doença de Alzheimer/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , População Rural , Autorrelato
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