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1.
Small ; 20(22): e2309107, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38145322

RESUMO

Synthesis of upconversion nanoparticles (UCNPs)-metal halide perovskites (MHPs) heterostructure is garnered immense attentions due to their unparalleled photophysical properties. However, the obvious difference in their structural forms makes it a huge challenge. Herein, hexagonal ß-NaYF4 and hexagonal Cs4PbBr6 are filtrated to construct the UCNP/MHP heterostructural luminescent material. The similarity in their crystal structures facilitate the heteroepitaxial growth of Cs4PbBr6 on the surface of ß-NaYF4 NPs, leading to the formation of high-quality ß-NaYF4:Yb,Tm/Cs4PbBr6 core/shell nanocrystals (NCs). Interestingly, this heterostructure endows the core/shell NCs with typically narrow-band green emission centered at 524 nm under 980 nm excitation, which should be attributed to the Förster resonance energy transfer (FRET) from Tm3+ to Cs4PbBr6. It is noteworthy that the FRET efficiency of ß-NaYF4:Yb,Tm/Cs4PbBr6 core/shell NCs (58.33%) is much higher than that of the physically mixed sample (1.84%). In addition, the reduced defect density, lattice anchoring effect, as well as diluted ionic bonding proportion induced by the core/shell structure further increase the excellent water-resistance and thermal cycling stability of Cs4PbBr6. These findings open up a new way to construct UCNP/MHP heterostructure with better multi-code luminescence performance and stability and promote its wide optoelectronic applications.

2.
Small ; 19(34): e2300047, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37127869

RESUMO

Numerous structures have been functionally optimized for directional liquid transport in nature. Inspired by lush trees' xylem that enable liquid directional transportation from rhizomes to the tip of trees, a new kind of programmable microfluidic porous matrices using projection micro-stereolithography (PµSL) based 3D printing technique is fabricated. Structural matrices with internal superhydrophilicity and external hydrophobicity are assembled for ultra-fast liquid rising enabled by capillary force. Moreover, the unidirectional microfluidic performance of the bionic porous matrices can be theoretically optimized by adjusting its geometric parameters. Most significantly, the successive programmable flow of liquid in a preferred direction inside the bionic porous matrices with tailored wettability is achieved, validating by a precisely printed liquid displayer and a microfluidic logic chip. The programmable and functional microfluidic matrices promise applications of patterned liquid flow, displayer, logic chip, cell screening, gas-liquid separation, and so on.

3.
J Nutr ; 152(12): 2922-2930, 2023 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-36130233

RESUMO

BACKGROUND: Two billion people are affected by anemia globally, mostly including women of reproductive age (WRA) and those residing in low- and middle-income countries (LMICs). Large national population-representative studies examining the impact of national grain fortification policies on the prevalence of anemia among WRA are lacking from recent years. OBJECTIVES: We aimed to determine whether mandatory national grain fortification policies reduce the prevalence of anemia among nonpregnant WRA. METHODS: We examined national food fortification policy characteristics from the Global Fortification Data Exchange (GFDx) database and anemia prevalence data from the Demographic and Health Surveys (DHSs). In total, 21 LMICs, with and without national grain fortification policies, completing ≥2 DHSs between 2000 and 2018, met study eligibility. We applied the difference-in-differences approach to compare changes in the prevalence of anemia among WRA in 10 countries with and 11 countries without fortification between each DHS year. Odds ratios (ORs) and average marginal effects, along with 95% confidence intervals (CIs) were calculated, adjusting for individual-, household-, and country-level factors. RESULTS: Our analytic study sample included 96,334 and 874,984 WRA in countries with and without fortification, respectively. Overall, countries with fortification showed 27% decreased odds of anemia (adjusted OR: 0.73; 95% CI: 0.63, 0.85) and a 7.47-percentage-point decrease in the mean anemia prevalence (average marginal effect: -7.47; 95% CI: -11.03, -3.92) from the pre- to the postfortification period, compared with countries without fortification, after controlling for selected individual-, household-, and country-level factors. CONCLUSIONS: Our findings, using nationally representative DHS data and applying a recommended analytic method to measure policy effectiveness, suggest significant reductions in anemia prevalence in WRA in countries with mandatory grain fortification compared with those without. Implementing national mandatory grain fortification in LMICs would effectively reduce anemia resulting from micronutrient deficiencies among WRA.


Assuntos
Anemia , Alimentos Fortificados , Humanos , Feminino , Prevalência , Anemia/epidemiologia , Anemia/prevenção & controle , Reprodução , Micronutrientes
4.
Acta Pharmacol Sin ; 44(3): 561-572, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35986213

RESUMO

Nitidine chloride (NC) is a standard active component from the traditional Chinese medicine Zanthoxylum nitidum (Roxb.) DC. (ZN). NC has shown a variety of pharmacological activities including anti-tumor activity. As a number of anti-tumor drugs cause cardiotoxicity, herein we investigated whether NC exerted a cardiotoxic effect and the underlying mechanism. Aqueous extract of ZN (ZNE) was intraperitoneally injected into rats, while NC was injected into beagles and mice once daily for 4 weeks. Cardiac function was assessed using echocardiography. We showed that both ZNE administered in rats and NC administered in mice induced dose-dependent cardiac hypertrophy and dysfunction, whereas administration of NC at the middle and high dose caused death in Beagles. Consistently, we observed a reduction of cardiac autophagy levels in NC-treated mice and neonatal mouse cardiomyocytes. Furthermore, we demonstrated that autophagy-related 4B cysteine peptidase (ATG4B) may be a potential target of NC, since overexpression of ATG4B reversed the cardiac hypertrophy and reduced autophagy levels observed in NC-treated mice. We conclude that NC induces cardiac hypertrophy via ATG4B-mediated downregulation of autophagy in mice. Thus, this study provides guidance for the safe clinical application of ZN and the use of NC as an anti-tumor drug.


Assuntos
Cardiomegalia , Cisteína Endopeptidases , Animais , Cães , Camundongos , Ratos , Autofagia , Benzofenantridinas/farmacologia , Cardiomegalia/induzido quimicamente , Cardiomegalia/genética , Peptídeo Hidrolases/efeitos dos fármacos , Cisteína Endopeptidases/efeitos dos fármacos
5.
Curr Issues Mol Biol ; 44(4): 1688-1700, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35723374

RESUMO

An accurate visual reporter system to assess homology-directed repair (HDR) is a key prerequisite for evaluating the efficiency of Cas9-mediated precise gene editing. Herein, we tested the utility of the widespread promoterless EGFP reporter to assess the efficiency of CRISPR/Cas9-mediated homologous recombination by fluorescence expression. We firstly established a promoterless EGFP reporter donor targeting the porcine GAPDH locus to study CRISPR/Cas9-mediated homologous recombination in porcine cells. Curiously, EGFP was expressed at unexpectedly high levels from the promoterless donor in porcine cells, with or without Cas9/sgRNA. Even higher EGFP expression was detected in human cells and those of other species when the porcine donor was transfected alone. Therefore, EGFP could be expressed at certain level in various cells transfected with the promoterless EGFP reporter alone, making it a low-resolution reporter for measuring Cas9-mediated HDR events. In summary, the widespread promoterless EGFP reporter could not be an ideal measurement for HDR screening and there is an urgent need to develop a more reliable, high-resolution HDR screening system to better explore strategies of increasing the efficiency of Cas9-mediated HDR in mammalian cells.

6.
Mov Disord ; 37(7): 1531-1535, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35507442

RESUMO

BACKGROUND: Wilson's disease (WD) currently lacks a promising indicator that could reflect neurological impairment and monitor treatment outcome. We aimed to investigate whether serum neurofilament light chain (sNfL) functions as a candidate for disease assessment and treatment monitoring of WD. METHODS: We assessed preclinical and manifested WD patients' sNfL levels compared to controls and analyzed the differences between patients with various clinical symptoms. We then explored the correlation between clinical scales and sNfL levels. And repeated measurements were performed in 34 patients before and after treatment. RESULTS: WD patients with neurological involvement had significantly higher sNfL levels than both hepatic patients and controls. Positive correlations were found between Unified Wilson's Disease Rating Scale scores and sNfL and between semiquantitative magnetic resonance imaging scales and sNfL levels in WD patients. However, in the treatment follow-up analysis, the trend of sNfL before and after treatment disaccorded with clinical response. CONCLUSION: These findings suggest that sNfL levels can be an ideal indicator for the severity of neurological involvement but fail to evaluate change in disease condition after treatment. © 2022 International Parkinson and Movement Disorder Society.


Assuntos
Degeneração Hepatolenticular , Biomarcadores , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/terapia , Humanos , Filamentos Intermediários , Imageamento por Ressonância Magnética , Resultado do Tratamento
7.
Mikrochim Acta ; 189(4): 140, 2022 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-35275270

RESUMO

A facile and rapid SERS strategy for S. typhimurium detection based on hybridization chain reaction (HCR) self-assembled G-quadruplex DNAzyme (GQH DNAzyme)-controlled plasmonic coupling was developed. GQH DNAzyme is introduced as a biocatalyst to catalyze the oxidation of L-cysteines to cysteines (thiols to disulfides) to assist SERS signal transduction. This is the first time that the self-assembled split GQH DNAzyme-controlled plasmonic coupling is integrated with SERS sensing. The results reveal the proposed SERS strategy can quantify S. typhimurium with a wide linear range (5 to 105 cfu mL-1) and a low detection limit (4 cfu mL-1; n = 5, mean ± standard deviation) and RSD of 7%. The method exhibited preeminent detection performance in spiked samples with recoveries of 93.1-117%. The proposed strategy has great potential for being a versatile SERS platform for detecting a wide spectrum of analytes by replacing them with the corresponding recognition elements. Therefore, this study not only creates a practical platform for pathogenic bacteria identification and related food safety testing and environmental monitoring, but also provides a new paradigm for building SERS sensor. A facile and rapid SERS strategy for S. Typhimurium detection based on hybridization chain reaction (HCR) self-assembled G-quadruplex DNAzyme-controlled plasmonic coupling.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Quadruplex G , Técnicas Biossensoriais/métodos , DNA Catalítico/metabolismo , Limite de Detecção , Salmonella typhimurium/genética , Salmonella typhimurium/metabolismo
8.
Clin Gastroenterol Hepatol ; 19(3): 590-596, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32485301

RESUMO

BACKGROUND & AIMS: Wilson disease is an autosomal recessive disorder that impairs copper homeostasis and is caused by homozygous or compound heterozygous mutations in ATP7B, which encodes a copper-transporting P-type ATPase. Patients have variable clinical manifestations and laboratory test results, resulting in diagnostic dilemmas. We aimed to identify factors associated with symptoms and features of Wilson disease from a large cohort, over 15 years. METHODS: We collected data from 715 patients (529 with symptoms, 146 without symptoms, and 40 uncategorized) and a genetic confirmation of Wilson's disease (mean age of diagnosis, 18.84 years), recruited from 3 hospitals in China from 2004 through 2019. We analyzed clinical data along with serum levels of ceruloplasmin (available from 636 patients), 24-hr urinary copper excretion (collected from 131 patients), Kayser-Fleisher rings (copper accumulation in eyes, with neurologic data from 355 patients), and magnetic resonance imaging (MRI) abnormalities. Differences among the groups were analyzed using 1-way analysis of variance followed by Tukey multiple comparison test. RESULTS: Of the 529 patients with symptoms, 121 had hepatic features, 355 had neurologic features, 28 had osteomuscular features (premature osteoarthritis, skeletal deformities, and pathological bone fractures), and 25 had psychiatric symptoms. Age of onset was significantly younger in patients with hepatic (16.94 ± 1.03 years; P = .0105) or osteomuscular features (13 ± 1.33 years; P = .0001) than patients with neurological features (19.48 ± 0.46 years). Serum levels of ceruloplasmin differed among asymptomatic patients and patients with osteomuscular or neurologic symptoms of Wilson disease. Serum levels of ceruloplasmin ranged from 18.93 mg/L to approximately 120.00 mg/L (quantiles of 0.025 to approximately 0.975). Fifty-one of 131 patients (39%) had urinary copper excretion levels below 100 µg/24 hr; there was significant variation in levels of urinary copper excretion between patients older than 14 years vs 14 years or younger. Of the 355 patients with neurologic features, 244 patients (69%) had abnormal findings from MRI and Kayser-Fleisher rings; only 1 patient with abnormal findings from brain MRI was negative for Kayser-Fleisher rings. CONCLUSIONS: Serum level of ceruloplasmin, 24-hour urinary copper excretion, and Kayser-Fleisher rings can be used to identify patients who might have Wilson disease. Patients with serum levels of ceruloplasmin below 120 mg/L and children with urinary copper excretion above 40 µg should undergo genetic testing for Wilson's disease. Patients with movement disorders and brain MRI abnormalities without Kayser-Fleisher rings are not likely to have Wilson disease.


Assuntos
Degeneração Hepatolenticular , Adolescente , Ceruloplasmina/metabolismo , Criança , Cobre/metabolismo , Testes Genéticos , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/genética , Humanos
9.
Metab Brain Dis ; 36(8): 2273-2281, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34347207

RESUMO

Aceruloplasminemia (ACP) is a rare disorder of iron overload resulting from ceruloplasmin (CP) variants. Because of its rarity and heterogeneity, the diagnosis of ACP is often missed or misdiagnosed. Here, we aim to present a clinical spectrum of ACP and raise more attention to the early diagnosis. Whole exome sequencing (WES) was performed in a Chinese female patient suspected with ACP and her clinical data were collected in detail. The PubMed databases was searched for published ACP patients within the last decade, and we present a systematic review of their clinical features with data extracted from these researches. A novel pathogenic variant (c.2689delC) and a known pathogenic variant (c.606dupA) within ceruloplasmin gene were identified in our patient and confirmed the diagnosis of ACP. Then we reviewed 51 ACP patients including the case we reported here. A possible timeline of symptoms was discovered, anemia appears first (29.7 years old on average), followed by diabetes (37.3 years old) and finally neurological symptoms (50.7 years old). The delay in diagnosis was significantly shortened in patients without neurological symptoms. Biochemical triad including anemia, low to undetectable serum ceruloplasmin, low serum iron and/or hyperferritinemia, showed better sensitivity in diagnosis than clinical triad including diabetes, neurological symptoms, and retinal degeneration. Due to the variable symptom spectrum, patients with ACP often visit different departments, which can lead to misdiagnosis. Clinical attention needs to be paid to symptoms and tests that have a warning effect. Prompt diagnosis in the early stage of the disease can be beneficial.


Assuntos
Ceruloplasmina , Distúrbios do Metabolismo do Ferro , Adulto , Ceruloplasmina/deficiência , Ceruloplasmina/genética , Ceruloplasmina/metabolismo , China , Feminino , Humanos , Distúrbios do Metabolismo do Ferro/diagnóstico , Distúrbios do Metabolismo do Ferro/genética , Distúrbios do Metabolismo do Ferro/patologia , Pessoa de Meia-Idade , Mutação/genética , Doenças Neurodegenerativas
10.
Mikrochim Acta ; 188(8): 255, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264390

RESUMO

As an extremely important post-transcriptional regulator, miRNAs are involved in a variety of crucial biological processes, and the abnormal expressions of miRNAs are closely related to a variety of diseases. In this work, for the first time, we designed a nucleic acid lock nanostructure for specific detection of miRNA-21, which changes the self-structure to "active conformation" by binding the target, in order to generate triggers to initiate the subsequent reaction. Emphatically, this flexible nucleic acid lock is capable of self-cleaving without the assistance of external component, overcoming the disadvantages of the complex design and requiring protease assistance in traditional nanostructure. Moreover, the combination of DNAzyme and RCA technology not only greatly improves the efficiency of signal amplification but also enables primer generation to simultaneous cascade RCA amplification. Additionally, the electrochemical detection technology based on silver nanoclusters overcomes the shortcomings of traditional detection methods such as low sensitivity and complex operation. The detection limit achieved was 9.3 aM with a wide dynamic response ranging from 10 aM to 100 pM (at the DPV peak of - 0.5 V), which is comparable to most of the reported studies. Therefore, our work provided an ultra-sensitive way for the detection of miRNAs using nanostructures and revealed an effective means for disease theranostics and cancer diagnosis. In this work, for the first time, we designed a nucleic acid lock nanostructure based on its self-structural transformation for the specific detection of miRNA. And the combination of DNAzyme and cascade RCA reaction greatly improved the signal amplification efficiency.


Assuntos
DNA Catalítico/química , DNA/química , MicroRNAs/química , Sequência de Bases , Técnicas Biossensoriais , Técnicas Eletroquímicas , Células HeLa , Humanos , Limite de Detecção , Células MCF-7 , Nanopartículas Metálicas/química , Técnicas de Amplificação de Ácido Nucleico , Prata/química
11.
J Am Chem Soc ; 141(25): 10091-10098, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31146522

RESUMO

Molybdenum nitrogenase catalyzes the reduction of dinitrogen into ammonia, which requires the coordinated transfer of eight electrons to the active site cofactor (FeMoco) through the intermediacy of an [8Fe-7S] cluster (P-cluster), both housed in the molybdenum-iron protein (MoFeP). Previous studies on MoFeP from two different organisms, Azotobacter vinelandii ( Av) and Gluconacetobacter diazotrophicus ( Gd), have established that the P-cluster is conformationally flexible and can undergo substantial structural changes upon two-electron oxidation to the POX state, whereby a backbone amidate and an oxygenic residue (Ser or Tyr) ligate to two of the cluster's Fe centers. This redox-dependent change in coordination has been implicated in the conformationally gated electron transfer in nitrogenase. Here, we have investigated the role of the oxygenic ligand in Av MoFeP, which natively contains a Ser ligand (ßSer188) to the P-cluster. Three variants were generated in which (1) the oxygenic ligand was eliminated (ßSer188Ala), (2) the P-cluster environment was converted to the one in Gd MoFeP (ßPhe99Tyr/ßSer188Ala), and (3) two oxygenic ligands were simultaneously included (ßPhe99Tyr). Our studies have revealed that the P-cluster can become compositionally labile upon oxidation and reversibly lose one or two Fe centers in the absence of the oxygenic ligand, while still retaining wild-type-like dinitrogen reduction activity. Our findings also suggest that Av and Gd MoFePs evolved with specific preferences for Ser and Tyr ligands, respectively, and that the structural control of these ligands must extend beyond the primary and secondary coordination spheres of the P-cluster. The P-cluster adds to the increasing number of examples of inherently labile Fe-S clusters whose compositional instability may be an obligatory feature to enable redox-linked conformational changes to facilitate multielectron redox reactions.


Assuntos
Proteínas de Bactérias/química , Proteínas Ferro-Enxofre/química , Nitrogenase/química , Azotobacter vinelandii/enzimologia , Proteínas de Bactérias/genética , Gluconacetobacter/enzimologia , Proteínas Ferro-Enxofre/genética , Mutação , Nitrogenase/genética , Oxirredução , Conformação Proteica , Estabilidade Proteica , Serina/química , Tirosina/química
12.
Med Sci Monit ; 22: 4786-4793, 2016 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-27924072

RESUMO

BACKGROUND Endometrial lesions are common in obstetrics and gynecology, including endometrial polyps, uterine adenomyosis, and malignant endometrial adenocarcinoma. Endometrial lesions seriously affect women's health, fertility, quality of life, and life safety. As a pro-apoptosis gene, p53 is considered to be closely related with human tumors. Murine double mimute 2 (MDM2) is an oncogene that can promote tumor occurrence and development. P53 and MDM2 expression and significance in different types of endometrial lesions have not been fully elucidated. MATERIAL AND METHODS Normal endometrium, endometrial polyps, uterine adenomyosis, and endometrial adenocarcinoma tissue samples were collected. Real-time PCR was used to detect p53 and MDM2 mRNA expression. Immunohistochemical staining and Western blot analysis were applied to test p53 and MDM2 protein expression. Their correlation with clinical staging of endometrial adenocarcinoma was analyzed. RESULTS P53 and MDM2 mRNA and protein expression were significantly elevated in the endometrial polyps group and the endometrial adenocarcinoma group compared with the normal control group (P<0.05). Their levels increased more obviously in endometrial adenocarcinoma compared with endometrial polyps (P<0.05). P53 and MDM2 mRNA and protein expression were slightly enhanced in uterine adenomyosis compared with normal controls, but this difference lacked statistical significance (P>0.05). P53 and MDM2 mRNA and protein level showed a positive correlation. Significantly higher expression of p53 or MDM2 was observed in patients with stage III compared to those in patients with stage II. Higher expression was also observed in patients with stage II than in patients with stage I. CONCLUSIONS P53 and MDM2 mRNA and protein were elevated in endometrial polyps and endometrial adenocarcinoma and their expressions were correlated with clinical staging of endometrial adenocarcinoma. They can promote cancer occurrence and development, and can be treated to assist diagnosis and provide a reference for treatment.


Assuntos
Neoplasias do Endométrio/metabolismo , Proteínas Proto-Oncogênicas c-mdm2/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenomiose/genética , Adenomiose/metabolismo , Adenomiose/patologia , Adulto , Idoso , Diagnóstico Diferencial , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pólipos/genética , Pólipos/metabolismo , Pólipos/patologia , Proteínas Proto-Oncogênicas c-mdm2/genética , Qualidade de Vida , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteína Supressora de Tumor p53/genética
13.
Pharmaceuticals (Basel) ; 17(4)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38675484

RESUMO

Zanthoxylum nitidum (Roxb.) DC. (Z. nitidum) is a traditional Chinese medicinal plant that is indigenous to the southern regions of China. Previous research has provided evidence of the significant anti-inflammatory, antibacterial, and anticancer properties exhibited by Z. nitidum. The potential therapeutic effects and cardiac toxicity of Z. nitidum remain uncertain. The aim of this research was to investigate the potential therapeutic properties of the four main compounds of Z. nitidum in cardiovascular diseases, their impact on the electrical activity of cardiomyocytes, and the underlying mechanism of their anti-inflammatory effects. We selected the four compounds from Z. nitidum with a high concentration and specific biological activity: nitidine chloride (NC), chelerythrine chloride (CHE), magnoflorine chloride (MAG), and hesperidin (HE). A proteomic analysis was conducted on the myocardial tissues of beagle dogs following the administration of NC to investigate the role of NC in vivo and the associated biological processes. A bioinformatic analysis was used to predict the in vivo biological processes that MAG, CHE, and HE were involved in. Molecular docking was used to simulate the binding between compounds and their targets. The effect of the compounds on ion channels in cardiomyocytes was evaluated through a patch clamp experiment. Organ-on-a-chip (OOC) technology was developed to mimic the physiological conditions of the heart in vivo. Proteomic and bioinformatic analyses demonstrated that the four compounds of Z. nitidum are extensively involved in various cardiovascular-related biological pathways. The findings from the patch clamp experiments indicate that NC, CHE, MAG, and HE elicit a distinct activation or inhibition of the IK1 and ICa-L in cardiomyocytes. Finally, the anti-inflammatory effects of the compounds on cardiomyocytes were verified using OOC technology. NC, CHE, MAG, and HE demonstrate anti-inflammatory effects through their specific interactions with prostaglandin-endoperoxide synthase 2 (PTGS2) and significantly influence ion channels in cardiomyocytes. Our study provides a foundation for utilizing NC, CHE, MAG, and HE in the treatment of cardiovascular diseases.

14.
Biochem Pharmacol ; 226: 116381, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38909786

RESUMO

The escalating prevalence of obesity presents formidable challenges, necessitating the development of effective therapeutic strategies. In this study, we aimed to elucidate the preventive effects on obesity of tetrahydroberberrubine (THBru), a derivative of berberine (BBR) and to unravel its underlying mechanism. Using an obese mouse model induced by a high-fat diet (HFD), THBru was found to markedly ameliorate obesity, as evidenced by reduced body weight, decreased Lee's index, diminished fat mass in epididymal white adipose tissue (WAT) and brown adipose tissue (BAT), alongside improved dyslipidemia. Notably, at the same dose, THBru exhibited superior efficacy compared to BBR. RNA-sequencing and gene set enrichment analysis indicated THBru activated thermogenesis, which was further confirmed in WAT, BAT, and 3T3-L1 cells. Bioinformatics analysis of RNA-sequencing data revealed the candidate gene Pgc1α, a key regulator involved in thermogenesis. Moreover, THBru was demonstrated to elevate the expression of PGC1α by stabilizing its mRNA in WAT, BAT and 3T3-L1 cells. Furthermore, PGC1α knockdown blocked the pro-thermogenic and anti-obesity action of THBru both in vivo and in vitro. This study unravels the preventive effects of THBru on obesity through the activation of PGC1α-mediated thermogenesis, thereby delineating its potential therapeutic implications for obesity and associated disorders.

16.
J Mol Diagn ; 25(1): 57-67, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36343861

RESUMO

Wilson disease (WD) is a hereditary disorder of copper metabolism, resulting from mutations within ATP7B. Early diagnosis is essential for affected individuals. However, there are still patients with clinically suspected WD who do not have detectable pathogenic variants, which makes diagnosis difficult and delays treatment. This study included such patients from the authors' center and screened for the full-length sequence of ATP7B by next-generation sequencing. Newly identified synonymous and intronic variants were then analyzed with in silico tools. A minigene system was constructed to determine the pathogenicity of these variants in terms of splicing and blood RNA extraction, and RT-PCR experiments were performed on several patients to verify the splicing alterations. The phenotypes of the patients were also analyzed. Fourteen suspected pathogenic variants, including nine synonymous and five intronic variants, were detected in 12 patients with clinically suspected WD. Among them, four synonymous variants (c.1050G>A, c.1122C>G, c.3243G>A, and c.4014T>A) and four intronic variants (c.1543 +40G>A, c.1707+6_1707+16del, c.1870-49A>G, and c.2731-67A>G) resulted in splicing changes in ATP7B. After the above analysis, the diagnosis of WD could be confirmed in eight clinically suspected patients with WD who showed a late age of onset.


Assuntos
ATPases Transportadoras de Cobre , Degeneração Hepatolenticular , Humanos , Degeneração Hepatolenticular/diagnóstico , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/metabolismo , Íntrons/genética , Mutação , Splicing de RNA/genética , Virulência , ATPases Transportadoras de Cobre/genética
17.
J Nutr Educ Behav ; 55(9): 644-650, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37395692

RESUMO

OBJECTIVE: To examine the association between food insecurity and dysfunctional eating behaviors among adults in Puerto Rico. METHODS: Data from 865 participants were obtained from baseline interviews from the Puerto Rico Observational Study of Psychosocial, Environmental, and Chronic Disease Trends (PROSPECT) cohort. The association between food insecurity and emotional eating (EE) and uncontrolled eating (UE) (categorized as no/moderate/high) was examined using multinomial logistic models. Potential mediation by perceived stress was explored. RESULTS: The prevalence of food insecurity was 20.3%. Compared with adults with food security, adults with food insecurity had higher odds of both moderate EE (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.18-3.09) and high EE (OR, 2.85; 95% CI, 1.75-4.64), and both moderate UE (OR, 1.78; 95% CI, 0.91-3.50) and high UE (OR, 3.28; 95% CI, 1.70-6.33). Perceived stress slightly attenuated these associations. CONCLUSIONS AND IMPLICATIONS: Food insecurity was associated with a higher likelihood of engaging in dysfunctional eating behaviors. Interventions alleviating food insecurity or stress might help adults sustain healthy eating behaviors.


Assuntos
Comportamento Alimentar , Abastecimento de Alimentos , Humanos , Adulto , Porto Rico/epidemiologia , Emoções , Insegurança Alimentar
18.
Chem Sci ; 14(33): 8914-8923, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37621427

RESUMO

Recently, the polarization effect has been receiving tremendous attention, as it can result in improved stability and charge transfer efficiency of metal-halide perovskites (MHPs). However, realizing the polarization effect on CsPbX3 NCs still remains a challenge. Here, metal ions with small radii (such as Mg2+, Li+, Ni2+, etc.) are introduced on the surface of CsPbX3 NCs, which facilitate the arising of electric dipole and surface polarization. The surface polarization effect promotes redistribution of the surface electron density, leading to reinforced surface ligand bonding, reduced surface defects, near unity photoluminescence quantum yields (PLQYs), and enhanced stability. Moreover, further introduction of hydroiodic acid results in the in situ formation of tert-butyl iodide (TBI), which facilitates the successful synthesis of pure iodine-based CsPbI3 NCs with high PLQY (95.3%) and stability under ambient conditions. The results of this work provide sufficient evidence to exhibit the crucial role of the surface polarization effect, which promotes the synthesis of high-quality MHPs and their applications in the fields of optoelectronic devices.

19.
Heliyon ; 9(6): e17347, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37441410

RESUMO

Background: Increasing evidence has shown that the risk of tuberculosis (TB) might be related to the exposure to air pollutants; however, the findings are inconsistent and studies on long-term air pollutant exposure and TB risk are scarce. This study aime to assess the relationship between monthly exposure to air pollution and TB risk in Nantong, China. Methods: We collected the time series data on the number of TB cases, as well as environmental and socioeconomic covariates from January 2005 to December 2020. The impact of air pollutant exposure on TB risk was evaluated using the distributed lag nonlinear model (DLNM). Stratified analyses were conducted to examine the effect modifications of sex and age on the association between air pollutants and TB risk. Sensitivity analyses were applied to test the stability of the model. Results: There were a total of 54,096 cases of TB in Nantong during the study period. In the single-pollutant model, for each 10 µg/m3 increase in concentration, the pooled relative risks (RRs) of TB reached the maximum to 1.10 (95% confidence interval (CI): 1.04-1.16, lag 10 months) for particulate matter with aerodynamic diameter less than 2.5 µm (PM2.5), 1.05 (95% CI: 1.01-1.10, lag 9 months) for particulate matter with aerodynamic diameter less than 10 µm (PM10), and 1.11 (95%CI: 1.04-1.19, lag 10 months) for nitrogen dioxide (NO2). Ozone (O3) did not show significant effect on TB risk. Effect modifications of sex and age on the association between air pollutants and TB risk were not observed. The multi-pollutant model results showed no significant variation compared with the single-pollutant model. Conclusions: Our study suggests that air pollutants pose a substantial threat to the TB risk. Reducing air pollution might be crucial for TB prevention and control.

20.
Talanta ; 252: 123833, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36057165

RESUMO

Statistics show that food poisoning caused by Salmonella typhimurium (S. Typhimurium) often tops the list of bacterial food poisoning types in countries around the world. However, detecting traces of S. Typhimurium in real samples remains challenging. In recent years, primer exchange reaction (PER), a new isothermal amplification strategy, has rapidly attracted the attention of researchers in the field of biosensing. In this work, We developed a nanostructure called DNA arch bridge (DAB) and combined the DAB with cascade PER technology to construct a novel bidirectional PER (B-PER) for ultra-sensitive detection of pathogenic bacteria as a novel fluorescent biosensor. This strategy relies on the B-PER reaction mediated by binding of the target and adaptor, which occurs with the assistance of Klenow Fragment (KF) (3'-5'exo) polymerase and produces a good deal of G-quadruplex sequences that generate a fluorescent signal by embedding fluorescent dyes. Under the best conditions, the biosensor achieves ultrasensitive detection of S. Typhimurium, and the detection limit of the strategy is 9.3 cfu mL-1 over the linear detection scope of 101-105 cfu mL-1. The method has the merits of facile operation, rapid response, and high sensitivity. Furthermore, the biosensor is expected to achieve ultrasensitive detection of various small molecules through recognizing different target and primer sequences. Therefore, our proposed strategy provides an efficient, stable, universal, and practical sensing platform for pathogen and other small molecules detection.


Assuntos
Técnicas Biossensoriais , Doenças Transmitidas por Alimentos , Humanos , Salmonella typhimurium/genética , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico/métodos , Técnicas Biossensoriais/métodos , DNA/genética , Corantes Fluorescentes/química
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