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1.
Acad Radiol ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38582684

RESUMO

RATIONALE AND OBJECTIVES: To explore and validate the clinical value of ultrasound (US) viscosity imaging in differentiating breast lesions by combining with BI-RADS, and then comparing the diagnostic performances with BI-RADS alone. MATERIALS AND METHODS: This multicenter, prospective study enrolled participants with breast lesions from June 2021 to November 2022. A development cohort (DC) and validation cohort (VC) were established. Using histological results as reference standard, the viscosity-related parameter with the highest area under the receiver operating curve (AUC) was selected as the optimal one. Then the original BI-RADS would upgrade or not based on the value of this parameter. Finally, the results were validated in the VC and total cohorts. In the DC, VC and total cohorts, all breast lesions were divided into the large lesion, small lesion and overall groups respectively. RESULTS: A total of 639 participants (mean age, 46 years ± 14) with 639 breast lesions (372 benign and 267 malignant lesions) were finally enrolled in this study including 392 participants in the DC and 247 in the VC. In the DC, the optimal viscosity-related parameter in differentiating breast lesions was calculated to be A'-S2-Vmax, with the AUC of 0.88 (95% CI: 0.84, 0.91). Using > 9.97 Pa.s as the cutoff value, the BI-RADS was then modified. The AUC of modified BI-RADS significantly increased from 0.85 (95% CI: 0.81, 0.88) to 0.91 (95% CI: 0.87, 0.93), 0.85 (95% CI: 0.80, 0.89) to 0.90 (95% CI: 0.85, 0.93) and 0.85 (95% CI: 0.82, 0.87) to 0.90 (95% CI: 0.88, 0.92) in the DC, VC and total cohorts respectively (P < .05 for all). CONCLUSION: The quantitative viscous parameters evaluated by US viscosity imaging contribute to breast cancer diagnosis when combined with BI-RADS.

2.
Front Mol Neurosci ; 17: 1365978, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660385

RESUMO

Non-coding RNAs (ncRNAs) play essential regulatory functions in various physiological and pathological processes in the brain. To systematically characterize the ncRNA profile in cortical cells, we downloaded single-cell SMART-Seq v4 data of mouse cerebral cortex. Our results revealed that the ncRNAs alone are sufficient to define the identity of most cortical cell types. We identified 1,600 ncRNAs that exhibited cell type specificity, even yielding to distinguish microglia from perivascular macrophages with ncRNA. Moreover, we characterized cortical layer and region specific ncRNAs, in line with the results by spatial transcriptome (ST) data. By constructing a co-expression network of ncRNAs and protein-coding genes, we predicted the function of ncRNAs. By integrating with genome-wide association studies data, we established associations between cell type-specific ncRNAs and traits related to neurological disorders. Collectively, our study identified differentially expressed ncRNAs at multiple levels and provided the valuable resource to explore the functions and dysfunctions of ncRNAs in cortical cells.

3.
Chem Commun (Camb) ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647208

RESUMO

Mycotoxin contamination in food products may cause serious health hazards and economic losses. The effective control and accurate detection of mycotoxins have become a global concern. Even though a variety of methods have been developed for mycotoxin detection, most conventional methods suffer from complicated operation procedures, low sensitivity, high cost, and long assay time. Therefore, the development of simple and sensitive methods for mycotoxin assay is highly needed. The introduction of nucleic acid signal amplification technology (NASAT) into aptasensors significantly improves the sensitivity and facilitates the detection of mycotoxins. Herein, we give a comprehensive review of the recent advances in NASAT-based aptasensors for assaying mycotoxins and summarize the principles, features, and applications of NASAT-based aptasensors. Moreover, we highlight the challenges and prospects in the field, including the simultaneous detection of multiple mycotoxins and the development of portable devices for field detection.

4.
Membranes (Basel) ; 14(3)2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38535280

RESUMO

Proton ceramic fuel cells offer numerous advantages compared with conventional fuel cells. However, the practical implementation of these cells is hindered by the poor sintering activity of the electrolyte. Despite extensive research efforts to improve the sintering activity of BCZY, the systematic exploration of the utilization of NiO as a sintering additive remains insufficient. In this study, we developed a novel BaCe0.55Zr0.35Y0.1O3-δ (BCZY) electrolyte and systematically investigated the impact of adding different amounts of NiO on the sintering activity and electrochemical performance of BCZY. XRD results demonstrate that pure-phase BCZY can be obtained by sintering the material synthesized via solid-state reaction at 1400 °C for 10 h. SEM analysis revealed that the addition of NiO has positive effects on the densification and grain growth of BCZY, while significantly reducing the sintering temperature required for densification. Nearly fully densified BCZY ceramics can be obtained by adding 0.5 wt.% NiO and annealing at 1350 °C for 5 h. The addition of NiO exhibits positive effects on the densification and grain growth of BCZY, significantly reducing the sintering temperature required for densification. An anode-supported full cell using BCZY with 0.5 wt.% NiO as the electrolyte reveals a maximum power density of 690 mW cm-2 and an ohmic resistance of 0.189 Ω cm2 at 650 °C. Within 100 h of long-term testing, the recorded current density remained relatively stable, demonstrating excellent electrochemical performance.

5.
Front Oncol ; 14: 1356778, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38549944

RESUMO

Introduction: Triple-negative breast cancer (TNBC) is characterized by its aggressive nature and absence of specific therapeutic targets, necessitating the reliance on chemotherapy as the primary treatment modality. However, the drug resistance poses a significant challenge in the management of TNBC. In this study, we investigated the role of DDX58 (DExD/H-box helicase 58), also known as RIG-I, in TNBC chemoresistance. Methods: The relationship between DDX58 expression and breast cancer prognosis was investigated by online clinical databases and confirmed by immunohistochemistry analysis. DDX58 was knockout by CRISPR-Cas9 system (DDX58-KO), knockdown by DDX58-siRNA (DDX58-KD), and stably over expressed (DDX58-OE) by lentivirus. Western blotting, immunofluorescence and qPCR were used for related molecules detection. Apoptosis was analyzed through flow cytometry (Annexin V/7AAD apoptosis assay) and Caspase 3/7 activity assay. Results: Patients with lower expression of DDX58 led to lower rate of pathological complete response (pCR) and worse prognosis by online databases and hospital clinical data. DDX58-KD cells showed multiple chemo-drugs resistance (paclitaxel, doxorubicin, 5-fluorouracil) in TNBC cell lines. Similarly, DDX58-KO cells also showed multiple chemo-drugs resistance in a dosage-dependent manner. In the CDX model, tumours in the DDX58-KO group had a 25% reduction in the tumour growth inhibition rate (IR) compared to wild-type (WT) group after doxorubicin (Dox) treatment. The depletion of DDX58 inhibited proliferation and promoted the migration and invasion in MDA-MB-231 cells. The findings of our research indicated that DDX58-KO cells exhibit a reduction in Dox-induced apoptosis both in vivo and in vitro. Mechanistically, Dox treatment leads to a significant increase in the expression of double-stranded RNAs (dsRNAs) and activates the DDX58-Type I interferon (IFN) signaling pathway, ultimately promoting apoptosis in TNBC cells. Discussion: In the process of TNBC chemotherapy, the deficiency of DDX58 can inhibit Dox-induced apoptosis, revealing a new pathway of chemotherapy resistance, and providing a possibility for developing personalized treatment strategies based on DDX58 expression levels.

6.
J Sci Food Agric ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38497362

RESUMO

BACKGROUND: Due to the high level of organic acids - primarily citric acid - black, red, and white currants have an excessively sour taste, making taste adjustment during processing challenging. This study investigated and evaluated the effects of an inoculation dose of the acid-reducing yeast Issatchenkia terricola WJL-G4 on several aspect such as physicochemical properties, chromaticity, active substances, and antioxidant capacity. A sensory evaluation was also conducted. RESULTS: The results indicated that, when the inoculation dose increased from 2% to 12%, the total phenol, total flavonoid, and total anthocyanin content, and antioxidant capacity in currant juice decreased. A low inoculation dose (2-4%) was beneficial for preserving the total phenol and total flavonoid content. Although the levels of most phenolic compounds decreased, the concentrations of caffeic acid, p-coumaric acid, ferulic acid, rutin, and epicatechin were significantly higher than the control after fermentation. Overall acceptability and taste scores of fermented currants improved compared with those of the control group. CONCLUSION: This experiment provided an effective solution, with a theoretical basis, to the problems of the sour taste and harsh flavor of currant juice. © 2024 Society of Chemical Industry.

7.
Food Funct ; 15(7): 3752-3764, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38506160

RESUMO

This study aimed to elucidate the effect of tyrosol (TYR) on the amelioration of nonalcoholic fatty liver disease (NAFLD). Male C57BL/6J mice were fed a low-fat diet (LFD), a high-fat diet (HFD), or a HFD supplemented with 0.025% (w/w) TYR (TYR) for 16 weeks. Following a 16-week intervention, the TYR cohort exhibited diminished final body weight and hepatic lipid accumulation, compared to HFD fed mice. Liver metabolomics analysis revealed that TYR increased the hepatic levels of spermidine, taurine, linoleic acid, malic acid and eicosapentaenoic acid (EPA), indicating the beneficial effect of TYR on lipid homeostasis. Using molecular docking analysis and the luciferase assay, we found that TYR acts as a ligand and binds with peroxisome proliferator-activated receptor-α (PPARα), which plays a pivotal role in the modulation of hepatic lipid metabolism, thereby activating the transcription of downstream genes. Our results suggest that TYR alleviates NAFLD in HFD-fed mice probably by the modulation of the PPARα signaling pathway.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Álcool Feniletílico/análogos & derivados , Humanos , Masculino , Animais , Camundongos , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Metabolismo dos Lipídeos , Dieta Hiperlipídica/efeitos adversos , PPAR alfa/genética , PPAR alfa/metabolismo , Simulação de Acoplamento Molecular , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Lipídeos/farmacologia
8.
Food Chem ; 447: 138954, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-38461716

RESUMO

Real-time optical sensing of mercury has been developed rapidly in recent years but remains challenging such as bearing background interference. Herein, a Hg2+ and base dual-activatable ultrasensitive chemiluminescent probe CL-Hg based on benzothiazole-phenoxyl-dioxetane with profits of excitation light-free and minimal interference is presented. The photophysical properties study and sensing performance verified CL-Hg is coupled with unique advantages of long-term detection (more than 400 min), ultrahigh sensitivity (LOD = 0.52 nM), and high specificity to Hg2+, and visualization detection by the paper-based test strips. More importantly, CL-Hg showed the qualitative and quantitative detection capability for Hg2+ with great recyclability in real samples of water, seafood, and beverages, holding great potential for on-site monitoring of Hg2+ levels in the actual samples. To our knowledge, this is the first work achieving the detection of Hg2+ by chemiluminescence. Overall, the Hg2+-activated visualization platform offers a practical method for detecting Hg2+ in various application scenarios.


Assuntos
Mercúrio , Mercúrio/análise , Água , Bebidas , Corantes Fluorescentes
9.
Science ; 383(6688): 1245-1252, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38484052

RESUMO

The minor spliceosome, which is responsible for the splicing of U12-type introns, comprises five small nuclear RNAs (snRNAs), of which only one is shared with the major spliceosome. In this work, we report the 3.3-angstrom cryo-electron microscopy structure of the fully assembled human minor spliceosome pre-B complex. The atomic model includes U11 small nuclear ribonucleoprotein (snRNP), U12 snRNP, and U4atac/U6atac.U5 tri-snRNP. U11 snRNA is recognized by five U11-specific proteins (20K, 25K, 35K, 48K, and 59K) and the heptameric Sm ring. The 3' half of the 5'-splice site forms a duplex with U11 snRNA; the 5' half is recognized by U11-35K, U11-48K, and U11 snRNA. Two proteins, CENATAC and DIM2/TXNL4B, specifically associate with the minor tri-snRNP. A structural analysis uncovered how two conformationally similar tri-snRNPs are differentiated by the minor and major prespliceosomes for assembly.


Assuntos
Íntrons , RNA Nuclear Pequeno , Spliceossomos , Humanos , Microscopia Crioeletrônica , Ribonucleoproteínas Nucleares Pequenas/química , Sítios de Splice de RNA , Splicing de RNA , RNA Nuclear Pequeno/química , Spliceossomos/química , Conformação de Ácido Nucleico
10.
J Appl Microbiol ; 135(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38449343

RESUMO

AIMS: This study aimed to investigate the changes of cell membrane structure and function of Issatchenkia terricola under citric acid by performing physiological analysis. METHODS AND RESULTS: The membrane integrity, surface hydrophobicity, structure, fluidity, apoptosis, and fatty acid methyl esters composition of I. terricola WJL-G4 cells were determined by propidium iodide staining, microbial adhesion to hydrocarbon test, transmission electron microscopy analysis, fluorescence anisotropy, flow cytometry, and gas chromatography-mass, respectively. The results showed that with the increasing of citric acid concentrations, the cell vitality, membrane integrity, and fluidity of I. terricola reduced; meanwhile, apoptosis rate, membrane permeable, hydrophobicity, and ergosterol contents augmented significantly. Compared to control, the activities of Na+, K+-ATPase, and Ca2+, Mg2+-ATPase increased by 3.73-fold and 6.70-fold, respectively, when citric acid concentration increased to 20 g l-1. The cells cracked and their cytoplasm effused when the citric acid concentration reached 80 g l-1. CONCLUSIONS: I. terricola could successfully adjust its membrane structure and function below 60 g l-1 of citric acid. However, for citric acid concentrations above 80 g l-1, its structure and function were dramatically changed, which might result in reduced functionality.


Assuntos
Estruturas da Membrana Celular , Ácido Cítrico , Pichia , Ácido Cítrico/farmacologia , Ácidos Graxos/farmacologia , Membrana Celular , Fluidez de Membrana
11.
Front Plant Sci ; 15: 1344972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38425798

RESUMO

Over the past several decades, a decreasing trend in solar radiation has been observed during the wheat growing season. The effects of shade stress on grain yield formation have been extensively studied. However, little information on shade stress's effects on protein formation warrants further investigation. Two wheat cultivars were grown under three treatments, no shade as the control group (CK), shading from the joint to the anthesis stage (S1), and shading from the joint to the mature stage (S2), to investigate the effects of shade stress on the free amino acids of the caryopsis and endosperm and protein accumulation during grain filling. The dry mass of caryopsis and endosperm was significantly decreased under shade stress, whereas Glu, Ser, Ala, and Asp and protein relative content increased during grain filling. The observed increases in total protein in S1 and S2 were attributed to the increases in the SDS-isoluble and SDS-soluble protein extracts, respectively. S1 improved polymer protein formation, but S2 delayed the conversion of albumins and globulins into monomeric and polymeric proteins. Moreover, shade stress increased the proportion of SDS-unextractable polymeric protein, which represented an increase in the degree of protein polymerization. The polymerization of protein interrelations between protein components and accumulation in caryopsis and endosperm provided novel insights into wheat quality formation under shade stress.

12.
Sci Rep ; 14(1): 5963, 2024 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472340

RESUMO

After ecological restoration of high and steep slopes in the project disturbed area, soil properties, soil microorganisms, litter types and root types change with the succession of vegetation cover communities. However, the effects of different vegetation successional stages on soil respiration dynamics remain unclear. To elucidate trends and drivers of soil respiration in the context of vegetation succession, we used spatio-temporal alternative applied research. Vegetated concrete-restored slopes (VC) with predominantly herbaceous (GS), shrub (SS), and arborvitae (AS) vegetation were selected, and naturally restored slopes (NS) were used as control. SRS1000 T soil carbon flux measurement system was used to monitor soil respiration rate. The results showed that soil respiration (RS) and fractions of all four treatments showed a single-peak curve, with peaks concentrated in July and August. During the succession of vegetation from herbaceous to arborvitae on VC slopes, RS showed a decreasing trend, and GS was significantly higher than AS by 45%; Compared to NS, RS was 29.81% and 21.56% higher in GS and SS successional stages, respectively, and 27.51% lower in AS stage. RS was significantly and positively correlated with nitrate nitrogen (NO3--N) and microbial biomass nitrogen (MBN), both of which are important factors in regulating RS under vegetation succession. A bivariate model of soil temperature and water content explains the variability of Rs better. Overall, RS was higher than NS in the transition stage and lower than NS in the equilibrium stage of the vegetation community on VC slopes, and the RS decreases gradually with the vegetation succession of artificial ecological restoration slopes.


Assuntos
Carbono , Solo , Carbono/análise , Biomassa , Nitrogênio/análise , Microbiologia do Solo , Ecossistema , China
13.
Biomed Opt Express ; 15(2): 1021-1037, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38404321

RESUMO

We present a fully automatic montage pipeline for adaptive optics SLO retinal images. It contains a flexible module to estimate the translation between pairwise images. The user can change modules to accommodate the alignment of the dataset using the most appropriate alignment technique, provided that it estimates the translation between image pairs and provides a quantitative confidence metric for the match between 0 and 1. We use these pairwise comparisons and associated metrics to construct a graph where nodes represent frames and edges represent the overlap relations. We use a small diameter spanning tree to determine the best pairwise alignment for each image based on the entire set of image relations. The final stage of the pipeline is a blending module that uses dynamic programming to improve the smoothness of the transition between frames. Data sets ranging from 26 to 119 images were obtained from individuals aged 24 to 81 years with a mix of visually normal control eyes and eyes with glaucoma or diabetes. The resulting automatically generated montages were qualitatively and quantitatively compared to results from semi-automated alignment. Data sets were specifically chosen to include both high quality and medium quality data. The results obtained from the automatic method are comparable or better than results obtained by an experienced operator performing semi-automated montaging. For the plug-in pairwise alignment module, we tested a technique that utilizes SIFT + RANSAC, Normalized cross-correlation (NCC) and a combination of the two. This pipeline produces consistent results not only on outer retinal layers, but also on inner retinal layers such as a nerve fiber layer or images of the vascular complexes, even when images are not of excellent quality.

14.
Food Chem ; 445: 138661, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38350195

RESUMO

To improve the poor water solubility and oral bioavailability of tyrosol, novel tyrosol liposomes (Tyr-LPs) were prepared by pH-driven method. Fourier transform infrared (FTIR) absorption spectra and X-ray diffraction (XRD) analysis indicated that Tyr-LPs were successfully encapsulated and tyrosol was in an amorphous state in liposomes. When tyrosol content in Tyr-LP was 1.33 mg/ml and the Tyr:LP (mass ratio) = 1:2, favorable dispersibility of Tyr-LP was exhibited, with an instability index of 0.049 ± 0.004, PDI of 0.274 ± 0.003, and the EE of 94.8 ± 2.5 %. In vivo pharmacokinetic studies showed that after oral administration of tyrosol or Tyr-LP (Tyr:LP = 1:2), concentration-versus-time curve (AUC0-720mins) and maximum concentration (Cmax) values of Tyr-LP was respectively 1.5-fold (P < 0.01) and 2.25-fold (P < 0.01) higher than tyrosol, which indicated that the oral bioavailability of tyrosol was effectively improved in Tyr-LPs. Our study thereby provides theoretical support for the application of Tyr-LP for optimal delivery of tryosol.


Assuntos
Lipopolissacarídeos , Lipossomos , Álcool Feniletílico/análogos & derivados , Ratos , Animais , Disponibilidade Biológica , Ratos Sprague-Dawley , Solubilidade , Administração Oral , Concentração de Íons de Hidrogênio
15.
Food Chem ; 445: 138708, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38387314

RESUMO

Raspberry leaves were subjected to steam explosion at 0.5 and 1.0 MPa for 60-120 s, aiming to disrupt their physical and chemical structure and, consequently, promote the release of phenolic compounds into the leaf aqueous infusion. Under optimal condition of 1.0 MPa for 60 s, steam explosion led to a notable 23 % increase in total phenolic content, a 29 % elevation in ABTS radical scavenging capacity, and a 13 % rise in DPPH radical scavenging capacity of the aqueous infusion. Utilizing UHPLC-Q-TOF-MS/MS and UHPLC-QE-MS/MS techniques, respectively, a total of 39 phenolic compounds were identified from raspberry leaves, and the changes in the contents of the most important 11 species were analyzed following steam explosion. Through correlation analysis and considering the content of each phenolic compound, it was inferred that the heightened antioxidant capacity of the aqueous infusion primarily stemmed from a substantial increase in the release of ellagic acid after steam explosion.


Assuntos
Rubus , Vapor , Água , Espectrometria de Massas em Tandem , Fenóis/análise , Antioxidantes/química , Nutrientes/análise , Folhas de Planta/química
16.
ACS Med Chem Lett ; 15(2): 230-238, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38352836

RESUMO

Herein, we disclose a powerful strategy for the functionalization of the antitumor natural alkaloid noscapine by utilizing photoredox/nickel dual-catalytic coupling technology. A small collection of 37 new noscapinoids with diverse (hetero)alkyl and (hetero)cycloalkyl groups and enhanced sp3 character was thus synthesized. Further in vitro antiproliferative activity screening and SAR study enabled the identification of 6o as a novel, potent, and less-toxic anticancer agent. Furthermore, 6o exerts superior cellular activity via an unexpected S-phase arrest mechanism and could significantly induce cell apoptosis in a dose-dependent manner, thereby further highlighting its potential in drug discovery as a promising lead compound.

17.
J Adv Res ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38341033

RESUMO

BACKGROUND: Plant-derived extracellular vesicles (PDEVs) are membrane vesicles characterized by a phospholipid bilayer as the basic skeleton that is wrapped by various functional components of proteins and nucleic acids. An increasing number of studies have confirmed that PDEVs can be a potential treatment of inflammatory bowel disease (IBD) and can, to some extent, compensate for the limitations of existing therapies. AIM OF REVIEW: This review summarizes the recent advances and potential mechanisms underlying PDEVs obtained from different sources to alleviate IBD. In addition, the review discusses the possible applications and challenges of PDEVs, providing a theoretical basis for exploring novel and practical therapeutic strategies for IBD. KEY SCIENTIFIC CONCEPTS OF REVIEW: In IBD, the crosstalk mechanism of PDEVs may regulate the intestinal microenvironment homeostasis, especially immune responses, the intestinal barrier, and the gut microbiota. In addition, drug loading enhances the therapeutic potential of PDEVs, particularly regarding improved tissue targeting and stability. In the future, not only immunotherapy based on PDEVs may be an effective treatment for IBD, but also the intestinal barrier and intestinal microbiota will be a new direction for the treatment of IBD.

18.
BMC Biol ; 22(1): 29, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317233

RESUMO

BACKGROUND: Cyclic Nucleotide-Binding Domain (CNBD)-family channels display distinct voltage-sensing properties despite sharing sequence and structural similarity. For example, the human Ether-a-go-go Related Gene (hERG) channel and the Hyperpolarization-activated Cyclic Nucleotide-gated (HCN) channel share high amino acid sequence similarity and identical domain structures. hERG conducts outward current and is activated by positive membrane potentials (depolarization), whereas HCN conducts inward current and is activated by negative membrane potentials (hyperpolarization). The structural basis for the "opposite" voltage-sensing properties of hERG and HCN remains unknown. RESULTS: We found the voltage-sensing domain (VSD) involves in modulating the gating polarity of hERG. We identified that a long-QT syndrome type 2-related mutation within the VSD, K525N, mediated an inwardly rectifying non-deactivating current, perturbing the channel closure, but sparing the open state and inactivated state. K525N rescued the current of a non-functional mutation in the pore helix region (F627Y) of hERG. K525N&F627Y switched hERG into a hyperpolarization-activated channel. The reactivated inward current induced by hyperpolarization mediated by K525N&F627Y can be inhibited by E-4031 and dofetilide quite well. Moreover, we report an extracellular interaction between the S1 helix and the S5-P region is crucial for modulating the gating polarity. The alanine substitution of several residues in this region (F431A, C566A, I607A, and Y611A) impaired the inward current of K525N&F627Y. CONCLUSIONS: Our data provide evidence that a potential cooperation mechanism in the extracellular vestibule of the VSD and the PD would determine the gating polarity in hERG.


Assuntos
Canal de Potássio ERG1 , Ativação do Canal Iônico , Humanos , Sequência de Aminoácidos , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Ativação do Canal Iônico/genética , Mutação , Nucleotídeos Cíclicos , Canal de Potássio ERG1/genética
19.
Clin Exp Med ; 24(1): 42, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400850

RESUMO

Infection is the leading cause of morbidity and mortality in patients with multiple myeloma (MM). Studying the relationship between different traits of Coronavirus 2019 (COVID-19) and MM is critical for the management and treatment of MM patients with COVID-19. But all the studies on the relationship so far were observational and the results were also contradictory. Using the latest publicly available COVID-19 genome-wide association studies (GWAS) data, we performed a bidirectional Mendelian randomization (MR) analysis of the causality between MM and different traits of COVID-19 (SARS-CoV-2 infection, COVID-19 hospitalization, and severe COVID-19) and use multi-trait analysis of GWAS(MTAG) to identify new associated SNPs in MM. We performed co-localization analysis to reveal potential causal pathways between diseases and over-representation enrichment analysis to find involved biological pathways. IVW results showed SARS-CoV-2 infection and COVID-19 hospitalization increased risk of MM. In the reverse analysis, the causal relationship was not found between MM for each of the different symptoms of COVID-19. Co-localization analysis identified LZTFL1, MUC4, OAS1, HLA-C, SLC22A31, FDX2, and MAPT as genes involved in COVID-19-mediated causation of MM. These genes were mainly related to immune function, glycosylation modifications and virus defense. Three novel MM-related SNPs were found through MTAG, which may regulate the expression of B3GNT6. This is the first study to use MR to explore the causality between different traits of COVID-19 and MM. The results of our two-way MR analysis found that SARS-CoV-2 infection and COVID-19 hospitalization increased the susceptibility of MM.


Assuntos
COVID-19 , Mieloma Múltiplo , Humanos , Teorema de Bayes , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Mieloma Múltiplo/genética , COVID-19/genética , SARS-CoV-2/genética
20.
World Neurosurg ; 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38369106

RESUMO

OBJECTIVE: This study aimed to systematically evaluate the optimal surgical fusion approach for lumbar spondylolisthesis, to provide the latest and most reliable evidence for future clinical practice. METHODS: A comprehensive search of the PubMed, Ovid-Embase, Web of Science, Cochrane, and Scopus databases was conducted from inception to September 1, 2023, to identify relevant records. Two independent reviewers performed the literature screening, data extraction, and assessment of study quality. RESULTS: Fifteen randomized controlled trials involving 892 patients met the inclusion criteria. The network evidence plot showed that posterolateral fusion and posterior lumbar interbody fusion (PLIF) were the most used fusion techniques. The network meta-analysis results revealed that minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) had a significantly greater improvement in the Oswestry Disability Index (ODI) compared to endoscopic-TLIF, while PLIF had a significantly better fusion effect than posterolateral fusion. Furthermore, no statistically significant differences were observed between other fusion surgeries in terms of improving ODI, fusion rate, complications, or the improvement of visual analog scale-low back pain. The surface under the cumulative ranking curve results indicated that MIS-TLIF had the greatest potential for improving ODI, visual analog scale-low back pain, and complications, while PLIF had the greatest potential for increasing fusion rates. However, the existing selection bias, measurement bias, reporting bias, and publication bias may have reduced the reliability of the meta-analysis results. CONCLUSIONS: Among the various fusion surgeries for lumbar spondylolisthesis, MIS-TLIF appears to provide the greatest benefit to patients. However, more high-quality, large-scale studies are needed to further investigate the treatment efficacy of different fusion surgeries for lumbar spondylolisthesis.

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