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1.
Angew Chem Int Ed Engl ; : e202409006, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896505

RESUMO

Proton exchange membranes with high selectivity are urgently required in energy and electronic technologies. Nafion, a state-of-the-art commercial proton exchange membrane material, faces significant challenges. It suffers from the permeation of undesirable substances, like hydrogen in fuel cells and vanadium ions in redox flow batteries, due to the unmatched sizes between its ionic domains (3~5 nm) and these substances. In this work, we present a supramolecular modification strategy that simultaneously enhances the proton conductivity and selectivity of Nafion. We employ fluoroalkyl-grafted polyoxometalate (POMs) nanoclusters as supramolecular additives to modify Nafion via co-assembly. These POMs can precisely and robustly decorate at Nafion ionic domains, with their fluoroalkyl chains anchoring into the perfluorinated matrix while their inorganic clusters stay in the ionic regions. The hybrid membranes, with continuous proton hopping sites and nanoscale steric hindrance offered by POMs, exhibit a 56% increase in proton conductivity and a 100% improvement in proton/vanadium selectivity. This leads to significantly enhanced power density and energy efficiency in fuel cells and vanadium flow batteries, respectively. These results underscore the intriguing potential of molecular cluster additives in improving the functions of ion-conducting membranes.

2.
Mol Immunol ; 172: 68-75, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38901181

RESUMO

OBJECTIVE: MicroRNA-23b-3p has been demonstrated to act as a safeguard against several autoimmune diseases. However, its role in Sjögren's syndrome (SS) remains unclear. METHODS: In order to investigate its role in SS, we administered agomiR-23b-3p or agomiR-NC to non-obese diabetic (NOD) mice via tail vein weekly for 6 weeks. The study examined the saliva flow rate, histological changes in submandibular glands, and levels of autoantibodies. Additionally, the levels of several cytokines, cell apoptosis, and NF-κB signaling were evaluated. The protective effect of miR-23b-3p was confirmed in a cell model. RESULTS: The results demonstrated that miR-23b-3p overexpression improved salivary flow rates, inhibited lymphocyte infiltration, reduced cytokine levels, and suppressed cell apoptosis in NOD mice. Moreover, NF-κB signaling was inactivated following miR-23b-3p overexpression. In a cellular model of SS, overexpression of miR-23b-3p protected submandibular gland epithelial cells exposed to IFN-γ against apoptosis and inflammation by targeting SOX6. CONCLUSIONS: The study concludes that miR-23b-3p alleviates SS by targeting SOX6 and inhibiting the NF-κB signaling pathway. The miR-23b-3p/SOX6 axis represents a promising avenue for the development of novel therapeutic strategies for SS.

3.
J Agric Food Chem ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905352

RESUMO

The overuse of antibiotics in animal farming and aquaculture has led to multidrug-resistant methicillin-sensitive Staphylococcus aureus (MR-MSSA) becoming a common pathogen in foodborne diseases. Sophora flavescens Ait. serves as a traditional plant antibacterial agent and functional food ingredient. A total of 30 compounds (1-30) were isolated from the root bark of S. flavescens, consisting of 20 new compounds (1-20). In the biological activity assay, compound 1 demonstrated a remarkable inhibitory effect on MR-MSSA, with an MIC of 2 µg/mL. Furthermore, 1 was found to rapidly eliminate bacteria, inhibit biofilm growth, and exhibit exceptionally low cytotoxicity. Mechanistic studies have revealed that 1 possesses an enhanced membrane-targeting ability, binding to the bacterial cell membrane components phosphatidylglycerol (PG), phosphatidylethanolamine (PE), and cardiolipin (CL). This disruption of bacterial cell membrane integrity increases intracellular reactive oxygen species, protein and DNA leakage, reduced bacterial metabolism, and ultimately bacterial death. In summary, these findings suggest that compound 1 holds promise as a lead compound against MR-MSSA.

4.
Geriatr Nurs ; 58: 238-246, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38838406

RESUMO

OBJECTIVE: To evaluate the effectiveness of home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices in patients with heart disease. METHODS: We searched eight electronic databases under the guidance of Cochrane Handbook and PRISMA recommendations. RESULTS: The meta-analysis included data from 14 articles (15 RCTs) representing 1314 participants. A significant improvement in left ventricular ejection fraction [MD = 2.12, 95 % CI (1.21, 3.04), P < 0.001], 6-minute walk distance [MD = 40.00, 95 % CI (21.72, 58.29), P < 0.001] and peak oxygen intake [MD = 2.24, 95 % CI (1.38, 3.10), P < 0.001] were observed in the home-based cardiac telerehabilitation group. But it had no difference in anxiety [SMD = -0.83, 95 % CI (-1.65, -0.02), P = 0.05] and depression [SMD = -0.59, 95 % CI (-1.26, 0.09), P = 0.09]. Subgroup analyses revealed that interventions of no less than 3 months improved anxiety [SMD = -1.11, 95 % CI (-2.05, -0.18), P = 0.02] and depression [SMD = -1.01, 95 % CI (-1.93, -0.08), P = 0.03]. CONCLUSION: Home-based cardiac telerehabilitation based on wearable electrocardiogram or heart rate monitoring devices has a positive effect on cardiac function. Long-term (≥ 3 months) cardiac rehabilitation might benefit individuals suffering from anxiety or depression.

5.
Talanta ; 277: 126335, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38823323

RESUMO

Developing a simple, economical, sensitive, and selective method for label-free direct detection analytes is attractive, especially the strategies that could achieve signal amplification without complicated operations. Herein, a dual-fluorescence colorimetric nanoswitch sensing platform for label-free direct melamine (MEL) detection was established. We first explored the relationship between MEL-induced aggregation of gold nanoparticles (AuNPs) and size and determined the optimal size to be 37 nm. Using surfactant Triton X-100 to modify AuNPs and clarify possible interaction mechanisms to improve detection performance. The dynamic changes of surface plasmon resonance absorption peaks in the dispersed and aggregated states of AuNPs were skillfully utilized to match the emission of multicolor gold nanoclusters to trigger the multi-inner filter effect. Accompanied by the addition of MEL-induced AuNPs to change from dispersed to aggregated state, the fluorescence of green-emitting and red-emitting gradually turned on and turned off, respectively. The fluorescence turn-on mode detection limit was 10 times higher than the colorimetric method and as low as 5.5 ng/mL; the detection took only 10 min. The sensor detected MEL in spiked milk samples with a good recovery in the range of 81.2-111.0 % with a coefficient of variation less than 11.4 % and achieved a good correlation with commercial kits. The proposed sensor integrates numerous merits of label-free, multi-signal readout, self-calibration, simple operations, and economical, which provides a promising tool for convenient on-site detection of MEL.

6.
Front Endocrinol (Lausanne) ; 15: 1394306, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38883600

RESUMO

Introduction: Iodine serves as a crucial precursor for the synthesis of thyroid hormones and plays an import role in both pregnant women and their offspring. The relationships between iodine nutritional status and maternal thyroid function and neonatal outcomes remain inconclusive in areas with adequate iodine nutrition. This study aims to investigate their correlations. Methods: Blood, morning urine and 24-hour urine were collected from the pregnant women to measure thyroid functions, serum iodine concentration (SIC), morning urine iodine concentration (UIC) and 24-hour urine iodine excretion (24-hour UIE). Indicators of their offspring's neonatal indexes were recorded. Results: A total of 559 pregnant women were enrolled in this study. The iodine indicators including Tg, 24-hour UIE and morning UIC were significantly different among the euthyroid pregnant women and those with different thyroid disorders. The levels of FT3, FT4, and SIC exhibited a gradual decline and the concentration of TSH exhibited a gradual increase trend throughout the progression of pregnancy in euthyroid pregnant women. There were no significant differences in neonatal outcomes and neonatal TSH values among euthyroid pregnant women and thyroid disorders pregnant women. SIC had a significant impact on maternal FT4 levels throughout all three trimesters, with varying degrees of importance observed in each trimester. TSH level emerged as the primary determinant of FT4 during the first trimester, while SIC exerted a predominant influence on FT4 levels in the second and third trimesters. The prevalence of thyroid disorders in pregnant women was the lowest when the SIC of pregnant women was probable in the range of 60~70 µg/L, 24-hours UIE was in the range of 250~450 µg, and Tg was in the range of 9~21 µg/L. Maternal TSH exhibited a notable influence on neonatal TSH levels, particularly at the 50th and 75th quantiles. Among the iodine nutritional indicators, SIC and morning UIC demonstrated higher AUC values for abnormal FT4 and TSH, respectively. Discussion: The iodine nutrition status of pregnant women exerts an impact on their thyroid function and prevalence of thyroid disorders, and neonatal TSH was affected by maternal TSH. SIC may be a better indicator for iodine nutritional assessment than other indexes.


Assuntos
Iodo , Estado Nutricional , Testes de Função Tireóidea , Glândula Tireoide , Tireotropina , Humanos , Feminino , Gravidez , Iodo/urina , Iodo/sangue , Tireotropina/sangue , Recém-Nascido , Adulto , Glândula Tireoide/fisiologia , Glândula Tireoide/metabolismo , Complicações na Gravidez/sangue , Complicações na Gravidez/epidemiologia , Doenças da Glândula Tireoide/sangue , Doenças da Glândula Tireoide/epidemiologia , Adulto Jovem
7.
Acta Pharm Sin B ; 14(5): 2097-2118, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38799640

RESUMO

Choline acetyltransferase (ChAT)-positive neurons in neural stem cell (NSC) niches can evoke adult neurogenesis (AN) and restore impaired brain function after injury, such as acute ischemic stroke (AIS). However, the relevant mechanism by which ChAT+ neurons develop in NSC niches is poorly understood. Our RNA-seq analysis revealed that dimethylarginine dimethylaminohydrolase 1 (DDAH1), a hydrolase for asymmetric NG,NG-dimethylarginine (ADMA), regulated genes responsible for the synthesis and transportation of acetylcholine (ACh) (Chat, Slc5a7 and Slc18a3) after stroke insult. The dual-luciferase reporter assay further suggested that DDAH1 controlled the activity of ChAT, possibly through hypoxia-inducible factor 1α (HIF-1α). KC7F2, an inhibitor of HIF-1α, abolished DDAH1-induced ChAT expression and suppressed neurogenesis. As expected, DDAH1 was clinically elevated in the blood of AIS patients and was positively correlated with AIS severity. By comparing the results among Ddah1 general knockout (KO) mice, transgenic (TG) mice and wild-type (WT) mice, we discovered that DDAH1 upregulated the proliferation and neural differentiation of NSCs in the subgranular zone (SGZ) under ischemic insult. As a result, DDAH1 may promote cognitive and motor function recovery against stroke impairment, while these neuroprotective effects are dramatically suppressed by NSC conditional knockout of Ddah1 in mice.

8.
FEBS J ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602252

RESUMO

Adaptation to hypoxia has attracted much public interest because of its clinical significance. However, hypoxic adaptation in the body is complicated and difficult to fully explore. To explore previously unknown conserved mechanisms and key proteins involved in hypoxic adaptation in different species, we first used a yeast model for mechanistic screening. Further multi-omics analyses in multiple species including yeast, zebrafish and mice revealed that glycerophospholipid metabolism was significantly involved in hypoxic adaptation with up-regulation of lysophospholipid acyltransferase (ALE1) in yeast, a key protein for the formation of dipalmitoyl phosphatidylcholine [DPPC (16:0/16:0)], which is a saturated phosphatidylcholine. Importantly, a mammalian homolog of ALE1, lysophosphatidylcholine acyltransferase 1 (LPCAT1), enhanced DPPC levels at the cell membrane and exhibited the same protective effect in mammalian cells under hypoxic conditions. DPPC supplementation effectively attenuated growth restriction, maintained cell membrane integrity and increased the expression of epidermal growth factor receptor under hypoxic conditions, but unsaturated phosphatidylcholine did not. In agreement with these findings, DPPC treatment could also repair hypoxic injury of intestinal mucosa in mice. Taken together, ALE1/LPCAT1-mediated DPPC formation, a key pathway of glycerophospholipid metabolism, is crucial for cell viability under hypoxic conditions. Moreover, we found that ALE1 was also involved in glycolysis to maintain sufficient survival conditions for yeast. The present study offers a novel approach to understanding lipid metabolism under hypoxia and provides new insights into treating hypoxia-related diseases.

9.
Clin Cosmet Investig Dermatol ; 17: 891-900, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660588

RESUMO

Purpose: The purpose of this study was to investigate the comprehensive impact of family history of psoriasis, lesion size, disease severity, and the possibility of joint involvement on patients' quality of life(QoL). Patients and Methods: Data from 5961 patients with psoriasis recruited from 440 hospitals throughout China were analyzed. The effects of family history of psoriasis, Body Surface Area(BSA), Psoriasis Area and Severity Index(PASI), and Psoriasis Epidemiology Screening Tool(PEST) on their Dermatology Life Quality Index(DLQI) were studied using a moderated chained mediated effects test. Results: A total of 912 patients (15.30%) had a family history of psoriasis, and 5071 patients (85.10%) had plaque psoriasis. In patients with plaque psoriasis, the variables of family history, PASI, PEST, and DLQI were positively correlated with each other. Additionally, in patients with other types of psoriasis, PASI was positively correlated with PEST and DLQI. Age was positively correlated with PASI and PEST and negatively correlated with DLQI in patients with plaque psoriasis; their Body Mass Index(BMI) and disease duration were in positive correlation with PASI and PEST. The mediation effect of PASI and PEST between family history and DLQI was remarkable in patients with plaque psoriasis and not in those with other types of psoriasis. BSA moderated the association between family history and PASI in patients with plaque psoriasis. Conclusion: PASI and PEST play a chain mediating role in the relationship between family history and DLQI in patients with plaque psoriasis, and high levels of BSA increase the ability of family history to positively predict PASI in plaque psoriasis, thereby affecting the patient's QoL.

10.
J Agric Food Chem ; 72(15): 8581-8594, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38590167

RESUMO

Our previous study showed that Lactiplantibacillus plantarum Y42 in the biofilm state can produce more exopolysaccharides and surface-layer proteins and showed a stronger promoting effect on intestinal barrier function than that in the planktonic state. In this study, oral administration of the live/pasteurized planktonic or biofilm L. plantarum Y42 and its metabolites (exopolysaccharides and surface-layer proteins) increased the expression of Occludin, Claudin-1, ZO-1, and MUC2 in the gut of the Balb/C mice after exposure to Listeria monocytogenes ATCC 19115 and inhibited the activation of the NLRP3 inflammasome pathway, which in turn reduced the levels of inflammatory cytokines IL-1ß and IL-18 in the serum of the mice. Furthermore, oral administration of the live/pasteurized planktonic or biofilm L. plantarum Y42 and its metabolites increased the abundance of beneficial bacteria (e.g., Lachnospiraceae_NK4A136_group and Prevotellaceae_UCG-001) while reducing the abundance of harmful bacteria (e.g., norank_f__Muribaculaceae) in the gut of the mice, in line with the increase of short-chain fatty acids and indole derivatives in the feces of the mice. Notably, biofilm L. plantarum Y42 exerted a better preventing effect on the intestinal barrier dysfunction of the Balb/C mice due to the fact that biofilm L. plantarumY42 expressed more exopolysaccharides and surface-layer proteins than the planktonic state. These results provide data support for the use of exopolysaccharides and surface-layer proteins extracted from biofilm-state L. plantarum Y42 as functional food ingredients in preventing intestinal barrier dysfunction.


Assuntos
Enteropatias , Listeria monocytogenes , Camundongos , Animais , Camundongos Endogâmicos BALB C , Citocinas , Biofilmes
11.
J Evid Based Integr Med ; 29: 2515690X241241859, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38544476

RESUMO

BACKGROUND: Pulse width, which can reflect qi, blood excess, and deficiency, has been used for diagnosing diseases and determining the prognosis in traditional Chinese medicine (TCM). This study aimed to devise an objective method to measure the pulse width based on an array pulse diagram for objective diagnosis. METHODS: The channel 6, the region wherein the pulse wave signal is the strongest, is located in the middle of the pulse sensor array and at the guan position of cunkou during data collection. Therefore, the main wave (h1) time of the pulse wave was collected from the channel 6 through calculation. The left h1 time was collected from the remaining 11 channels. The amplitudes at these time points were extracted as the h1 amplitudes for each channel. However, the pulse width could not be calculated accurately at 12 points. Consequently, a bioharmonic spline interpolation algorithm was used to interpolate the h1 amplitude data obtained from the horizontal and vertical points, yielding 651 (31 × 21) h1 amplitude data. The 651 data points were converted into a heat map to intuitively calculate the pulse width. The pulse width was calculated by multiplying the number of grids on the vertical axis with the unit length of the grid. The pulse width was determined by TCM doctors to verify the pulse width measurement accuracy. Meanwhile, a color Doppler ultrasound examination of the volunteers' radial arteries was performed and the intravascular meridian widths of the radial artery compared with the calculated pulse widths to determine the reliability. RESULTS: The pulse width determined using the maximal h1 amplitude method was comparable with the radial artery intravascular meridian widths measured using color Doppler ultrasound. The h1 amplitude was higher in the high blood pressure group and the pulse width was greater. CONCLUSIONS: The pulse width determined using the maximal h1 amplitude was objective and accurate. Comparison between the pulse widths of the normal and high blood pressure groups verified the reliability of the method.


Assuntos
Hipertensão , Humanos , Reprodutibilidade dos Testes , Frequência Cardíaca , Pressão Sanguínea/fisiologia , Medicina Tradicional Chinesa/métodos
12.
J Hazard Mater ; 469: 134068, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38521040

RESUMO

The abuse of olaquindox (OLA) as both an antimicrobial agent and a growth promoter poses significant threats to the environment and human health. While nanoreactors have proven effective in hazard detection, their widespread adoption has been hindered by tedious chemical processes and limited functionality. In this study, we introduce a novel green self-assembly strategy utilizing invertase, horseradish peroxidase, antibodies, and gold nanoclusters to form an aggregation-induced emission-type zeolitic imidazolate framework-8 nanoreactor. The results demonstrate that the lateral flow immunoassay not only allows for qualitative naked eye detection but also enables optical analysis through the fluorescence generated by aggregated gold nanoclusters and enzyme-catalyzed enhancement of visible colorimetric signals. To accommodate more detection scenarios, the photothermal effects and redox reactions of the nanoreactor can fulfill the requirements of thermal sensing and electrochemical analysis for smartphone applications. Remarkably, the proposed approach achieves a detection limit 17 times lower than conventional methods. Besides, the maximum linear range spans from 0.25 to 5 µg/L with high specificity, and the recovery is 85.2-112.9% in environmental water and swine urine. The application of this high-performance nanoreactor opens up avenues for the construction of multifunctional biosensors with great potential in monitoring hazardous materials.


Assuntos
Quinoxalinas , Smartphone , Zeolitas , Animais , Biônica , Ouro , Nanotecnologia , Suínos
13.
Anal Chim Acta ; 1298: 342384, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38462339

RESUMO

BACKGROUND: The utilization of inner filter effect (IFE) brings more opportunities for construction of fluorescence immunoassays but remains a great challenge, especially how to select best donor in the face of extensive fluorescent nanomaterials. Aflatoxin B1 possesses high toxicity among mycotoxins and is frequently found in agricultural products that may significantly threaten to human health. Therefore, with the help of signal transduction mechanism of IFE to develop a convenient and sensitive approach for AFB1 detection is of great significance in ensuring food safety. RESULTS: Herein, the classical alkaline phosphatase (ALP) catalyzes hydrolysis of p-nitrophenylphosphate to produce p-nitrophenol (PNP) was employed as a model reaction, which intends to explore tunable multicolor fluorescence of gold nanoclusters (AuNCs) for matching PNP to maximize IFE efficiency. The luminescent green-emitting AuNCs were selected as an optimal donor in terms of excellent spectral overlap, high photoluminescence, and adequate system adaptability, thus achieving a 22-fold increase in sensitivity improvement compared to colorimetric method for ALP detection. The fluorescence quenching mechanism between PNP and AuNCs was validated as IFE by studying ultraviolet absorption, zeta potentials and fluorescence lifetime. In light of this, we integrated a highly specific antibody-antigen recognition system, efficient enzymatic reaction and excellent optical characteristics of AuNCs to develop dual-mode immunoassay for AFB1 monitoring. The sensitivity of fluorometric immunoassay was lower to 0.06 ng/mL, which obtained a 3.5-fold improvement compared to "gold standard" ELISA. Their practicability and applicability were confirmed in the tap water, corn, wheat and peanuts samples. SIGNIFICANCE: This work provides an easy-to-understand screening procedure to select optimal donor-acceptor pairs in IFE analysis. Furthermore, we expect that integration of IFE-based signal conversion strategy into mature immunoassay not only extends the signal types, simplifies signal amplification steps, and reduces the false-positive/false-negative rates, but also provides a simple, convenient, and versatile strategy for monitoring of trace other contaminants.


Assuntos
Fosfatase Alcalina , Nanopartículas Metálicas , Humanos , Limite de Detecção , Fosfatase Alcalina/análise , Hidrólise , Espectrometria de Fluorescência/métodos , Fluorometria , Corantes
14.
Adv Healthc Mater ; 13(14): e2303839, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38334034

RESUMO

Metal-organic framework (MOF)-based drug delivery nanomaterials for cancer therapy have attracted increasing attention in recent years. Here, an enhanced chemodynamic anti-tumor therapy strategy by promoting the Fenton reaction by using core-shell zeolitic imidazolate framework-8 (ZIF-8)@Fe3O4 as a therapeutic platform is proposed. Carboxymethyl cellulose (CMC) is used as a stabilizer of Fe3O4, which is then decorated on the surface of ZIF-8 via the electrostatic interaction and serves as an efficient Fenton reaction trigger. Meanwhile, the pH-responsive ZIF-8 scaffold acts as a container to encapsulate the chemotherapeutic drug doxorubicin (DOX). The obtained DOX-ZIF-8@Fe3O4/CMC (DZFC) nanoparticles concomitantly accelerate DOX release and generate more hydroxyl radicals by targeting the lysosomes in cancer cells. In vitro and in vivo studies verify that the DZFC nanoparticles trigger glutathione peroxidase 4 (GPX4)-dependent ferroptosis via the activation of the c-Jun N-terminal kinases (JNK) signaling pathway, following to achieve the chemo/ferroptosis synergistic anti-tumor efficacy. No marked toxic effects are detected during DZFC treatment in a tumor-bearing mouse model. This composite nanoparticle remarkably suppresses the tumor growth with minimized systemic toxicity, opening new horizons for the next generation of theragnostic nanomedicines.


Assuntos
Doxorrubicina , Ferroptose , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Doxorrubicina/química , Doxorrubicina/farmacologia , Animais , Humanos , Camundongos , Ferroptose/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Antineoplásicos/química , Antineoplásicos/farmacologia , Carboximetilcelulose Sódica/química , Camundongos Nus , Zeolitas/química , Imidazóis
15.
Adv Mater ; 36(15): e2310306, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38194699

RESUMO

The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2+ lung cells during a viral infection cycle shall prevent viral Spike (S) protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, dual-drug-combined (TMPRSS2 inhibitor Camostat and CTSL inhibitor E-64d) nanocarriers (NCs) are constructed conjugated with an anti-human ACE2 (hACE2) antibody and employ Red Blood Cell (RBC)-hitchhiking, termed "Nanoengineered RBCs," for targeting lung cells. The significant therapeutic efficacy of the dual-drug-loaded nanoengineered RBCs in pseudovirus-infected K18-hACE2 transgenic mice is reported. Notably, the modular nanoengineered RBCs (anti-receptor antibody+NCs+RBCs) precisely target key proteases of host cells in the lungs to block the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of virus variations. These findings are anticipated to benefit the development of a series of novel and safe host-cell-protecting antiviral therapies.


Assuntos
COVID-19 , Catepsina L , SARS-CoV-2 , Inibidores de Serina Proteinase , Animais , Camundongos , Enzima de Conversão de Angiotensina 2/metabolismo , Catepsina L/antagonistas & inibidores , Catepsina L/metabolismo , COVID-19/prevenção & controle , COVID-19/virologia , Eritrócitos , Pulmão/metabolismo , Peptídeo Hidrolases/metabolismo , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Serina Endopeptidases/metabolismo , Inibidores de Serina Proteinase/farmacologia , Inibidores de Serina Proteinase/uso terapêutico
16.
Parasitol Res ; 123(1): 104, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38240890

RESUMO

Tetrahymenosis is caused by the ciliated protozoan Tetrahymena and is responsible for serious economic losses to the aquaculture industry worldwide. However, information regarding the molecular mechanism leading to tetrahymenosis is limited. In previous transcriptome sequencing work, it was found that one of the two ß-tubulin genes in T. pyriformis was significantly expressed in infected fish, we speculated that ß-tubulin is involved in T. pyriformis infecting fish. Herein, the potential biological function of the ß-tubulin gene in Tetrahymena species when establishing infection in guppies was investigated by cloning the full-length cDNA of this T. pyriformis ß-tubulin (BTU1) gene. The full-length cDNA of T. pyriformis BTU1 gene was 1873 bp, and the ORF occupied 1134 bp, whereas 5' UTR 434 bp, and 3' UTR 305 bp whose poly (A) tail contained 12 bases. The predicted protein encoded by T. pyriformis BTU1 gene had a calculated molecular weight of 42.26 kDa and pI of 4.48. Moreover, secondary structure analysis and tertiary structure prediction of BTU1 protein were also conducted. In addition, morphology, infraciliature, phylogeny, and histopathology of T. pyriformis isolated from guppies from a fish market in Harbin were also investigated. Furthermore, qRT-PCR analysis and experimental infection assays indicated that the expression of BTU1 gene resulted in efficient cell proliferation during infection. Collectively, our data revealed that BTU1 is a key gene involved in T. pyriformis infection in guppies, and the findings discussed herein provide valuable insights for future studies on tetrahymenosis.


Assuntos
Poecilia , Tetrahymena pyriformis , Tetrahymena , Animais , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Tetrahymena/genética , Poecilia/genética , DNA Complementar/metabolismo , Tetrahymena pyriformis/genética , Tetrahymena pyriformis/metabolismo , RNA Mensageiro/metabolismo
17.
Biol Trace Elem Res ; 202(1): 133-144, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37103640

RESUMO

The objective of the present study was to explore the effects of maternal iodine excess during pregnancy on infants' neurodevelopment and physical development. A total of 143 mother-child pairs were enrolled in this cohort study. Maternal blood samples were collected during the obstetric examination. A mother-child questionnaire survey was conducted, and infants' blood samples were collected during the newborn physical examination. Infants' single-spot urine samples were collected, and intellectual, motor, and physical development were assessed at 2 months of age. The median (IQR) maternal serum iodine concentrations (SICs) in the first, second, and third trimesters of pregnancy were 91.2 (74.4, 102.2) µg/L, 81.2 (70.6, 94.8) µg/L, and 82.0 (68.9, 100.3) µg/L, respectively. In the first trimester of pregnancy, infants' psychomotor developmental index (PDI), body mass index (BMI) and weight-for-length Z score (WLZ) were higher with maternal suitable SIC (40 ~ 92 µg/L) than with maternal excess SIC (P < 0.05). Infants' PDI, BMI, weight-for-age Z score (WAZ) and WLZ were negatively correlated with maternal SIC (P < 0.05). Maternal excess SIC had a slightly negative effect on infants' MDI (OR = 1.304, P = 0.035, 95% CI = 1.019 ~ 1.668), PDI (OR = 1.124, P = 0.001, 95% CI = 1.052 ~ 1.200) and BMI (OR = 0.790, P = 0.005, 95% CI = 0.669 ~ 0.933). In the third trimester, infants' length-for-age Z score (LAZ) was higher with maternal high SIC (> 92 µg/L) (P = 0.015), and maternal SIC was positively correlated with infants' urine iodine concentration (UIC) (P = 0.026). Maternal iodine excess in the first trimester had a slightly negative effect on infants' intellectual, motor, and physical development. In the third trimester, maternal iodine excess only may have a positive impact on infants' height. Additionally, maternal iodine status was closely related to infants' iodine status.


Assuntos
Iodo , Lactente , Gravidez , Recém-Nascido , Feminino , Humanos , Estudos de Coortes , Iodo/urina , Inquéritos e Questionários , Índice de Massa Corporal , Estado Nutricional
18.
J Eur Acad Dermatol Venereol ; 38(3): 496-512, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38073580

RESUMO

The prevalence rates of attention deficit hyperactivity disorder (ADHD), depression, anxiety and suicide are increasing in patients with atopic dermatitis (AD), although no research has systematically examined these trends yet. Here, we explore the prevalence of the occurrence of comorbidities, such as ADHD, depression, anxiety and suicide with AD. We searched seven electronic databases from inception to October 2022 to identify relevant studies, and the Agency for Healthcare Research and Quality (AHRQ) and Newcastle-Ottawa Scale (NOS) tools were used to assess the quality of observational studies. Statistical analysis was performed using R software. Publication bias was evaluated using Egger's and Begg's linear tests. The global prevalence rates of ADHD, depression, anxiety and suicidal ideation in patients with AD were 7%, 17%, 21% and 13%, respectively, between 1998 and October 2022. Among children (aged <18 years), North American children with AD had the highest prevalence rates of ADHD (10%), depression (13%) and anxiety (20%). Among the adult (aged ≥18 years) population, patients with AD in Africa had the highest prevalence rates of depression (36%) and anxiety (44%), while Asian adults with AD had the highest prevalence rates of ADHD (7%) and suicidal ideation (20%). These results highlight the high prevalence and comorbidity rates of mental illnesses with AD, which should be brought to the attention of patients with AD and their physicians.


Assuntos
Dermatite Atópica , Transtornos Mentais , Adolescente , Adulto , Humanos , Ansiedade/epidemiologia , Comorbidade , Dermatite Atópica/epidemiologia , Transtornos Mentais/epidemiologia , Saúde Mental , Prevalência , Estudos Observacionais como Assunto
19.
Int J Biol Macromol ; 256(Pt 1): 128310, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38007023

RESUMO

This study describes the cloning and characterization of Period 1a and Period 1b genes and the analysis of their mRNA and protein expression in Amur minnow (Phoxinus lagowskii) after exposure to different light cycles. The full-length P. lagowskii Per1a and Per1b genes encode proteins consisting of 1393 and 1409 amino acids, and share high homology with the per1 genes of other freshwater fish species. The Per1a and Per1b genes were widely expressed within the brain, eye, and peripheral tissues. The acrophase of the Per1a gene in the pituitary gland occurred during the dark phase at ZT15 (zeitgeber time 15, 12 L: 12 D) and ZT18 (8 L, 16 D), whereas the acrophase of the Per1b gene in the pituitary gland was observed during the light phase. Our study suggests that the expression of Per1a and Per1b in P. lagowskii varied depending on differences in circadian rhythm patterns. The results of our dual-luciferase reporter assays demonstrated that the P. lagowskii Per1b gene enhances the activation of NF-κB. This study is the first to examine the circadian clock gene Per1a and Per1b in the high-latitude fish P. lagowskii, offering valuable insights into the effects of different light periods on this fish species.


Assuntos
Relógios Circadianos , Cipriniformes , Animais , Relógios Circadianos/genética , Distribuição Tecidual , Ritmo Circadiano/genética , Cipriniformes/genética , RNA Mensageiro/genética , Clonagem Molecular
20.
Neurol Sci ; 45(4): 1447-1454, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37991640

RESUMO

Neurolymphomatosis (NL) is an uncommon malignant lymphoma characterized by selective infiltration of the central and peripheral nervous system. In this case report, we present a patient diagnosed with diffuse large B-cell lymphoma who initially manifested with peripheral neuropathy, primarily characterized by weakness of the left lower limb. By exploring its clinical manifestations, ancillary tests, and reviewing the relevant literature, we aim to deepen our understanding, diagnosis, and treatment of this disease. A 48-year-old male patient presented to the Department of Neurology, Hematology, and Neurosurgery with complaint of left lower limb weakness that had persisted for over 11 months. Initial laboratory tests and cerebrospinal fluid analysis yielded negative results. Electromyography examination indicated damage to the left lumbar plexus and iliac plexus nerves raising suspicions of nerve root involvement. Enhanced MRI of the lumbosacral plexus nerves revealed thickening and enhanced signals in left nerve roots at T12-L1, L1-2, and L3-4 levels. Additionally, local thickening and enhancement of signals were observed in the left erector spine muscle, psoas major, and iliopsoas muscles compared to the contralateral side. PEC/CT imaging displayed multiple soft tissue density shadows in the left foraminal area at the T12-1 and L1-2 levels. Bone marrow examination excluded hematological disease. Subsequent biopsy of the left foraminal nerve root at T12-L1 and the vertebral muscle at L3 level confirmed a diagnosis of diffuse large B-cell malignant lymphoma, indicating PNSL due to the involvement of multiple nerve roots. Following diagnosis, the patient underwent chemotherapy, resulting in the alleviation of his symptoms. Diagnosing PNSL can be challenging due to the nonspecific clinical manifestations and often inconclusive laboratory test results. Misdiagnosis and delayed diagnosis are common pitfalls. Electromyography may reveal damage to the affected peripheral nerves, while MR imaging might show nerve root thickening, and PET/CT can demonstrate increased lesion uptake. However, the definitive diagnosis relies on a biopsy of the lesion. Treatment for PNSL typically involves chemotherapy.


Assuntos
Linfoma Difuso de Grandes Células B , Neoplasias do Sistema Nervoso Periférico , Masculino , Humanos , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Sistema Nervoso Periférico/patologia , Neoplasias do Sistema Nervoso Periférico/diagnóstico , Nervos Periféricos
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