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1.
bioRxiv ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-39005376

RESUMO

Immune checkpoint inhibitors (ICIs) that target programmed cell death 1 (PD-1) have revolutionized cancer treatment by enabling the restoration of suppressed T-cell cytotoxic responses. However, resistance to single-agent ICIs limits their clinical utility. Combinatorial strategies enhance their antitumor effects, but may also enhance the risk of immune related adverse effects of ICIs. Prostaglandin (PG) E2, formed by the sequential action of the cyclooxygenase (COX) and microsomal PGE synthase (mPGES-1) enzymes, acting via its E prostanoid (EP) receptors, EPr2 and EPr4, promotes lymphocyte exhaustion, revealing an additional target for ICIs. Thus, COX inhibitors and EPr4 antagonists are currently being combined with ICIs potentially to enhance antitumor efficacy in clinical trials. However, given the cardiovascular (CV) toxicity of COX inhibitors, such combinations may increase the risk particularly of CV AEs. Here, we compared the impact of distinct approaches to disruption of the PGE2 synthesis /response pathway - global or myeloid cell specific depletion of mPges-1 or global depletion of Epr4 - on the accelerated atherogenesis in Pd-1 deficient hyperlipidemic (Ldlr-/-) mice. All strategies restrained the atherogenesis. While depletion of mPGES-1 suppresses PGE2 biosynthesis, reflected by its major urinary metabolite, PGE2 biosynthesis was increased in mice lacking EPr4, consistent with enhanced expression of aortic Cox-1 and mPges-1. Deletions of mPges-1 and Epr4 differed in their effects on immune cell populations in atherosclerotic plaques; the former reduced neutrophil infiltration, while the latter restrained macrophages and increased the infiltration of T-cells. Consistent with these findings, chemotaxis by bone-marrow derived macrophages from Epr4-/- mice was impaired. Epr4 depletion also resulted in extramedullary lymphoid hematopoiesis and inhibition of lipoprotein lipase activity (LPL) with coincident spelenomegaly, leukocytosis and dyslipidemia. Targeting either mPGES-1 or EPr4 may restrain lymphocyte exhaustion while mitigating CV irAEs consequent to PD-1 blockade.

2.
J Fluoresc ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874825

RESUMO

An iminocoumarin and tetraphenylethylene compound that exhibits aggregation-induced emission (AIE) and a significant Stokes shift (Δλ = 135 nm) in THF was created via the Knoevenagel condensation method. TPICBT could also be used as a ratiometric near-infrared fluorescent probe for the naked color identification of F- and H2S. It showed a large red shift (˃ 90 nm), good selectivity, and anti-interference. Test strip detection and cell imaging had both been accomplished using the probe. In addition, the probe could conveniently detect H2S produced during food spoilage without laboratory instruments.

3.
Small ; : e2401777, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38747025

RESUMO

Bismuth-based electrocatalysts are effective for carbon dioxide (CO2) reduction to formate. However, at room temperature, these materials are only available in solid state, which inevitably suffers from surface deactivation, declining current densities, and Faradaic efficiencies. Here, the formation of a liquid bismuth catalyst on the liquid gallium surface at ambient conditions is shown as its exceptional performance in the electrochemical reduction of CO2 (i.e., CO2RR). By doping a trace amount of bismuth (740 ppm atomic) in gallium liquid metal, a surface enrichment of bismuth by over 400 times (30 at%) in liquid state is obtained without atomic aggregation, achieving 98% Faradic efficiency for CO2 conversion to formate over 80 h. Ab initio molecular simulations and density functional theory calculations reveal that bismuth atoms in the liquid state are the most energetically favorable sites for the CO2RR intermediates, superior to solid Bi-sites, as well as joint GaBi-sites. This study opens an avenue for fabricating high-performing liquid-state metallic catalysts that cannot be reached by elementary metals under electrocatalytic conditions.

4.
Chembiochem ; : e202400082, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38670922

RESUMO

Chiral tertiary alcohols are important organic compounds in science as well as in industry. However, their preparation in enantiomerically pure form is still a challenge due to their complex structure and steric hindrances compared with primary and secondary alcohols, so kinetic resolution could be an attractive approach.  Lipase A from Candida antarctica (CAL-A) has been shown to catalyze the enantioselective esterification of various tertiary alcohols with excellent enantioselectivity but low activity. Here we report a mutagenesis study by rational design to improve CAL-A activity against tertiary alcohols. Single mutants of CAL-A were selected, expressed, immobilized and screened for esterification of the tertiary alcohol 1,2,3,4-tetrahydronaphthalene-1-ol. A double mutant V278S+S429G showed a 1.5-fold higher reaction rate than that of the wild type CAL-A, while maintaining excellent enantioselectivity.

5.
Heliyon ; 10(5): e26673, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38463867

RESUMO

Background and objective: Cerebral edema (CED) is a serious complication of acute ischemic stroke (AIS), especially in patients with large hemispheric infarction (LHI). Herein, a deep learning-based approach is implemented to extract CSF from T2-Weighted Imaging (T2WI) and evaluate the relationship between quantified cerebrospinal fluid and outcomes. Methods: Patients with acute LHI who underwent magnetic resonance imaging (MRI) were included. We used a deep learning algorithm to segment the CSF from T2WI. The hemispheric CSF ratio was calculated to evaluate its relationship with the degree of brain edema and prognosis in patients with LHI. Results: For the 93 included patients, the left and right cerebrospinal fluid regions were automatically extracted with a mean Dice similarity coefficient of 0.830. Receiver operating characteristic analysis indicated that hemispheric CSF ratio was an accurate marker for qualitative severe cerebral edema (area under receiver-operating-characteristic curve 0.867 [95% CI, 0.781-0.929]). Multivariate logistic regression analysis of functional prognosis showed that previous stroke (OR = 5.229, 95% CI 1.013-26.984), ASPECT≤6 (OR = 13.208, 95% CI 1.136-153.540) and low hemispheric CSF ratio (OR = 0.966, 95% CI 0.937-0.997) were significantly associated with higher chances for unfavorable functional outcome in patients with LHI. Conclusions: Automated assessment of CSF volume provides an objective biomarker of cerebral edema that can be leveraged to quantify the degree of cerebral edema and confirm its predictive effect on outcomes after LHI.

6.
Sci Rep ; 14(1): 4183, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378847

RESUMO

Melanoma is a malignant skin tumor. This study aimed to explore and assess the effect of novel biomarkers on the progression of melanoma. Differently expressed genes (DEGs) were screened from GSE3189 and GSE46517 datasets of Gene Expression Omnibus database using GEO2R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted based on the identified DEGs. Hub genes were identified and assessed using protein-protein interaction networks, principal component analysis, and receiver operating characteristic curves. Quantitative real-time polymerase chain reaction was employed to measure the mRNA expression levels. TIMER revealed the association between aldehyde dehydrogenase 2 (ALDH2) and tumor immune microenvironment. The viability, proliferation, migration, and invasion were detected by cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing, and transwell assays. Total 241 common DEGs were screened out from GSE3189 and GSE46517 datasets. We determined 6 hub genes with high prediction values for melanoma, which could distinguish tumor samples from normal samples. ALDH2, ADH1B, ALDH3A2, DPT, EPHX2, and GATM were down-regulated in A375 and SK-MEL-2 cells, compared with the human normal melanin cell line (PIG1 cells). ALDH2 was selected as the candidate gene in this research, presenting a high diagnostic and predictive value for melanoma. ALDH2 had a positive correlation with the infiltrating levels of immune cells in melanoma microenvironment. Overexpression of ALDH2 inhibited cell viability, proliferation, migration, and invasion of A375/SK-MEL-2 cells. ALDH2 is a new gene biomarker of melanoma, which exerts an inhibitory effect on melanoma.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Melanoma/patologia , Perfilação da Expressão Gênica , Biomarcadores , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Mapas de Interação de Proteínas/genética , Microambiente Tumoral/genética , Aldeído-Desidrogenase Mitocondrial/genética
7.
Neurooncol Adv ; 6(1): vdae013, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405203

RESUMO

Background: The T2-FLAIR mismatch sign (T2FM) has nearly 100% specificity for predicting IDH-mutant and 1p/19q noncodeleted astrocytomas (astrocytomas). However, only 18.2%-56.0% of astrocytomas demonstrate a positive T2FM. Methods must be considered for distinguishing astrocytomas from negative T2FM gliomas. In this study, positive T2FM gliomas were manually distinguished from nonenhancing gliomas, and then a support vector machine (SVM) classification model was used to distinguish astrocytomas from negative T2FM gliomas. Methods: Nonenhancing gliomas (regardless of pathological type or grade) diagnosed between January 2022 and October 2022 (N = 300) and November 2022 and March 2023 (N = 196) will comprise the training and validation sets, respectively. Our method for distinguishing astrocytomas from nonenhancing gliomas was examined and validated using the training set and validation set. Results: The specificity of T2FM for predicting astrocytomas was 100% in both the training and validation sets, while the sensitivity was 42.75% and 67.22%, respectively. Using a classification model of SVM based on radiomics features, among negative T2FM gliomas, the accuracy was above 85% when the prediction score was greater than 0.70 in identifying astrocytomas and above 95% when the prediction score was less than 0.30 in identifying nonastrocytomas. Conclusions: Manual screening of positive T2FM gliomas, followed by the SVM classification model to differentiate astrocytomas from negative T2FM gliomas, may be a more effective method for identifying astrocytomas in nonenhancing gliomas.

8.
Acad Radiol ; 31(3): 1082-1090, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37689557

RESUMO

RATIONALE AND OBJECTIVES: The peritumoral region of glioblastoma (GBM) is composed of infiltrating tumor cells and vasogenic edema, which are difficult to distinguish manually on MRI. To distinguish tumor cell infiltration and vasogenic edema in GBM peritumoral regions, it is crucial to develop a method that is precise, effective, and widely applicable. MATERIALS AND METHODS: We retrieved the image characteristics of 379,730 voxels (marker of tumor infiltration) from 28 non-enhanced gliomas and 365,262 voxels (marker of edema) from the peritumoral edema region of 14 meningiomas on conventional MRI sequences (T1-weighted image, the contrast-enhancing T1-weighted image, the T2-weighted image, the T2-fluid attenuated inversion recovery image, and the apparent diffusion coefficient map). Using the SVM classifier, a model for predicting tumor cell infiltration and vasogenic edema at the voxel level was developed. The accuracy of the model's predictions was then evaluated using 15 GBM patients who underwent stereotactic biopsies. RESULTS: The area under the curve (AUC), accuracy, sensitivity, and specificity of the prediction model were 0.93, 0.84, 0.83, and 0.85 in the training set, and 0.90, 0.82, 0.83, and 0.83 in the test set (704,992 voxels), respectively. The pathology verification of 28 biopsy points with an accuracy of 0.79. CONCLUSION: At the voxel level, it seems possible to forecast tumor cell infiltration and vasogenic edema in the peritumoral region of GBM based on conventional MRI sequences.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Glioblastoma/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética/métodos , Glioma/patologia , Edema/diagnóstico por imagem
9.
Clin Immunol ; 258: 109857, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38043757

RESUMO

Systemic lupus erythematosus (SLE) is a typical systemic autoimmune disease that manifests as skin rash, arthritis, lymphadenopathy, and multiple organ lesions. Epigenetics, including DNA methylation, histone modification, and non-coding RNA regulation, mainly affect the function and characteristics of cells through the regulation of gene transcription or translation. Increasing evidence indicates that there are a variety of complex epigenetic effects in patients with SLE, which interfere with the differentiation and function of T, and B lymphocytes, monocytes, and neutrophils, and enhance the expression of SLE-associated pathogenic genes. This paper summarizes our currently knowledge regarding pathogenesis of SLE, and introduces current advances in the epigenetic regulation of SLE from three aspects: immune function, inflammatory response, and lupus complications. We propose that epigenetic changes could be used as potential biomarkers and therapeutic targets of SLE.


Assuntos
Artrite , Lúpus Eritematoso Sistêmico , Humanos , Epigênese Genética , Metilação de DNA , Artrite/genética , Diferenciação Celular
10.
Adv Sci (Weinh) ; 10(33): e2303377, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37870208

RESUMO

Neural interfaces for stable access to the spinal cord (SC) electrical activity can benefit patients with motor dysfunctions. Invasive high-density electrodes can directly extract signals from SC neuronal populations that can be used for the facilitation, adjustment, and reconstruction of motor actions. However, developing neural interfaces that can achieve high channel counts and long-term intraspinal recording remains technically challenging. Here, a biocompatible SC hyperflexible electrode array (SHEA) with an ultrathin structure that minimizes mechanical mismatch between the interface and SC tissue and enables stable single-unit recording for more than 2 months in mice is demonstrated. These results show that SHEA maintains stable impedance, signal-to-noise ratio, single-unit yield, and spike amplitude after implantation into mouse SC. Gait analysis and histology show that SHEA implantation induces negligible behavioral effects and Inflammation. Additionally, multi-unit signals recorded from the SC ventral horn can predict the mouse's movement trajectory with a high decoding coefficient of up to 0.95. Moreover, during step cycles, it is found that the neural trajectory of spikes and low-frequency local field potential (LFP) signal exhibits periodic geometry patterns. Thus, SHEA can offer an efficient and reliable SC neural interface for monitoring and potentially modulating SC neuronal activity associated with motor dysfunctions.


Assuntos
Movimento , Neurônios , Humanos , Camundongos , Animais , Eletrodos , Neurônios/fisiologia , Movimento/fisiologia , Eletroencefalografia/métodos
11.
Heliyon ; 9(8): e18709, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37576301

RESUMO

Objective: To investigate the distribution of axial length (AL) and posterior staphyloma (PS) in congenital cataract (CC) patients. The correlation between AL and the concentration of tissue transglutaminase (TGM2) in the aqueous humor (AH) of cataractous eyes was also evaluated. Methods: Cross-sectional data were collected from 499 children with CC who underwent phacoemulsification, anterior vitrectomy, and IOL implantation. AL measured by IOLMaster or A-scan ultrasonography and the presence of PS examined by B-scan ultrasonography were recorded. TGM2 levels in AH of 15 CC patients with normal axial length (NAL) and 15 CC patients with PS or long axial length (LAL) were measured by enzyme-linked immunosorbent assay. Results: The presence of PS in congenital cataractous eyes was 11.02%, and the presence of PS + LAL in congenital cataractous eyes was 29.06%. The AH levels of TGM2 in the cataractous group with NAL were lower than those in the cataractous group with PS or LAL (P < 0.001). The concentration of TGM2 in AH were positively correlated with AL of the patients' eyes (P = 0.001). Additionally, we found that TGM2 expressed in the cytoplasm of lens epithelial cells of cataractous eyes, and the expression level increased with the AL value. Conclusions: This study begins to lay the groundwork for investigating the characteristics of PS and LAL in patients with CC. Furthermore, AL was positively correlated with AH levels of TGM2.

12.
Mol Biol Evol ; 40(6)2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37341536

RESUMO

Three prevalent SARS-CoV-2 variants of concern (VOCs) emerged and caused epidemic waves. It is essential to uncover advantageous mutations that cause the high transmissibility of VOCs. However, viral mutations are tightly linked, so traditional population genetic methods, including machine learning-based methods, cannot reliably detect mutations conferring a fitness advantage. In this study, we developed an approach based on the sequential occurrence order of mutations and the accelerated furcation rate in the pandemic-scale phylogenomic tree. We analyzed 3,777,753 high-quality SARS-CoV-2 genomic sequences and the epidemiology metadata using the Coronavirus GenBrowser. We found that two noncoding mutations at the same position (g.a28271-/u) may be crucial to the high transmissibility of Alpha, Delta, and Omicron VOCs although the noncoding mutations alone cannot increase viral transmissibility. Both mutations cause an A-to-U change at the core position -3 of the Kozak sequence of the N gene and significantly reduce the protein expression ratio of ORF9b to N. Using a convergent evolutionary analysis, we found that g.a28271-/u, S:p.P681H/R, and N:p.R203K/M occur independently on three VOC lineages, suggesting that coordinated changes of S, N, and ORF9b proteins are crucial to high viral transmissibility. Our results provide new insights into high viral transmissibility co-modulated by advantageous noncoding and nonsynonymous changes.


Assuntos
COVID-19 , COVID-19/genética , SARS-CoV-2/genética , Evolução Biológica , Mutação , Pandemias
13.
Neurobiol Dis ; 183: 106181, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37271287

RESUMO

Acquired peripheral hearing loss in midlife is considered the primary modifiable risk factor for dementia, while the underlying pathological mechanism remains poorly understood. Excessive noise exposure is the most common cause of acquired peripheral hearing loss in modern society. This study was designed to investigate the impact of noise-induced hearing loss (NIHL) on cognition, with a focus on the medial prefrontal cortex (mPFC), a brain region that is involved in both auditory and cognitive processes and is highly affected in patients with cognitive impairment. Adult C57BL/6 J mice were randomly assigned to a control group and seven noise groups: 0HPN, 12HPN, 1DPN, 3DPN, 7DPN, 14DPN, and 28DPN, which were exposed to broadband noise at a 123 dB sound pressure level (SPL) for 2 h and sacrificed immediately (0 h), 12 h, or 1, 3, 7, 14, or 28 days post-noise exposure (HPN, DPN), respectively. Hearing assessment, behavioral tests, and neuromorphological studies in the mPFC were performed in control and 28DPN mice. All experimental animals were included in the time-course analysis of serum corticosterone (CORT) levels and mPFC microglial morphology. The results illustrated that noise exposure induced early-onset transient serum CORT elevation and permanent moderate-to-severe hearing loss in mice. 28DPN mice, in which permanent NIHL has been verified, exhibited impaired performance in temporal order object recognition tasks concomitant with reduced structural complexity of mPFC pyramidal neurons. The time-course immunohistochemical analysis in the mPFC revealed significantly higher morphological microglial activation at 14 and 28 DPN, preceded by a remarkably higher amount of microglial engulfed postsynaptic marker PSD95 at 7 DPN. Additionally, lipid accumulation in microglia was observed in 7DPN, 14DPN and 28DPN mice, suggesting a driving role of lipid handling deficits following excessive phagocytosis of synaptic elements in delayed and sustained microglial abnormalities. These findings provide fundamentally novel information concerning mPFC-related cognitive impairment in mice with NIHL and empirical evidence suggesting the involvement of microglial malfunction in the mPFC neurodegenerative consequences of NIHL.


Assuntos
Perda Auditiva Provocada por Ruído , Camundongos , Animais , Perda Auditiva Provocada por Ruído/complicações , Perda Auditiva Provocada por Ruído/patologia , Microglia/patologia , Camundongos Endogâmicos C57BL , Transtornos da Memória , Lipídeos
14.
Int J Mol Sci ; 24(10)2023 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-37240034

RESUMO

Abnormal uterine bleeding is a common benign gynecological complaint and is also the most common symptom of endometrial cancer (EC). Although many microRNAs have been reported in endometrial carcinoma, most of them were identified from tumor tissues obtained at surgery or from cell lines cultured in laboratories. The objective of this study was to develop a method to detect EC-specific microRNA biomarkers from liquid biopsy samples to improve the early diagnosis of EC in women. Endometrial fluid samples were collected during patient-scheduled in-office visits or in the operating room prior to surgery using the same technique performed for saline infusion sonohysterography (SIS). The total RNA was extracted from the endometrial fluid specimens, followed by quantification, reverse transcription, and real-time PCR arrays. The study was conducted in two phases: exploratory phase I and validation phase II. In total, endometrial fluid samples from 82 patients were collected and processed, with 60 matched non-cancer versus endometrial carcinoma patients used in phase I and 22 in phase II. The 14 microRNA biomarkers, out of 84 miRNA candidates, with the greatest variation in expression from phase I, were selected to enter phase II validation and statistical analysis. Among them, three microRNAs had a consistent and substantial fold-change in upregulation (miR-429, miR-183-5p, and miR-146a-5p). Furthermore, four miRNAs (miR-378c, miR-4705, miR-1321, and miR-362-3p) were uniquely detected. This research elucidated the feasibility of the collection, quantification, and detection of miRNA from endometrial fluid with a minimally invasive procedure performed during a patient in-office visit. The screening of a larger set of clinical samples was necessary to validate these early detection biomarkers for endometrial cancer.


Assuntos
Neoplasias do Endométrio , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Biomarcadores Tumorais/genética , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/patologia , Endométrio/metabolismo , Transcrição Reversa , Biomarcadores
15.
Opt Express ; 31(8): 13518-13527, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37157488

RESUMO

A broadband, electrically controlled, reconfigurable, circularly polarized reflective metasurface is presented. The chirality of the metasurface structure is changed by switching active elements, which benefits from the tunable current distributions generated by the elaborately designed structure under x-polarized and y-polarized waves. Notably, the proposed metasurface unit cell maintains a good circular-polarization efficiency in a broadband range of 6.82-9.96 GHz (fractional bandwidth of 37%) with a phase difference of π between the two states. As a demonstration, a reconfigurable circularly polarized metasurface containing 8 × 8 elements was simulated and measured. The results verify that the proposed metasurface can flexibly control circularly polarized waves in a broadband, realizing beam splitting, mirror reflection, and other beam manipulations from 7.4 GHz to 9.9 GHz (fractional bandwidth of 28.9%) by simply adjusting the loaded active elements. The proposed reconfigurable metasurface may offer a promising approach to electromagnetic wave manipulation or communication systems.

16.
J Neuroradiol ; 50(2): 258-265, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35346748

RESUMO

PURPOSE: Epilepsy is a common symptom in patients with frontal lobe glioma. Tumor-related epilepsy was recently considered a type of network disease. Glioma can severely influence the integrity of the white matter network. The association between white matter network changes and presurgical epilepsy remains unclear in glioma patients. This study aims to identify alterations to the subcortical brain networks caused by glioma and glioma-related epilepsy. METHODS: Sixty-one patients with frontal lobe gliomas were enrolled and stratified into the epileptic and non-epileptic groups. Additionally, 14 healthy participants were enrolled after matching for age, sex, and education level. All participants underwent diffusion tensor imaging. Graph theoretical analysis was applied to reveal topological changes in their white matter networks. Regions affected by tumors were excluded from the analysis. RESULTS: Global efficiency was significantly decreased (p = 0.008), while the shortest path length increased (p = 0.02) in the left and right non-epileptic groups compared to the controls. A total of five edges exhibited decreased fiber count in the non-epileptic group (p < 0.05, false discovery rate-corrected). The topological properties and connectional edges showed no significant differences when comparing the epileptic groups and the controls. Additionally, the degree centrality of several nodes connected to the alternated edges was also diminished. CONCLUSIONS: Compared to the controls, the epilepsy groups showed raletively intact WM networks, while the non-epileptsy groups had damaged network with lower efficiency and longer path length. These findings indicated that the occurrence of glioma related epilepsy have association with white matter network intergrity.


Assuntos
Epilepsia , Glioma , Substância Branca , Humanos , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imagem de Tensor de Difusão/métodos , Encéfalo/patologia , Epilepsia/patologia , Lobo Frontal/diagnóstico por imagem , Glioma/complicações , Glioma/diagnóstico por imagem , Glioma/patologia
17.
Insect Sci ; 30(3): 758-770, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36342954

RESUMO

Temperature is one of the most important environmental factors that affect organisms, especially ectotherms, due to its effects on protein stability. Understanding the general rules that govern thermostability changes in proteins to adapt high-temperature environments is crucial. Here, we report the amino acid substitutions of phosphoglucose isomerase (PGI) related to thermostability in the Glanville fritillary butterfly (Melitaea cinxia, Lepidoptera: Nymphalidae). The PGI encoded by the most common allele in M. cinxia in the Chinese population (G3-PGI), which is more thermal tolerant, is more stable under heat stress than that in the Finnish population (D1-PGI). There are 5 amino acid substitutions between G3-PGI and D1-PGI. Site-directed mutagenesis revealed that the combination of amino acid substitutions of H35Q, M49T, and I64V may increase PGI thermostability. These substitutions alter the 3D structure to increase the interaction between 2 monomers of PGI. Through molecular dynamics simulations, it was found that the amino acid at site 421 is more stable in G3-PGI, confining the motion of the α-helix 420-441 and stabilizing the interaction between 2 PGI monomers. The strategy for high-temperature adaptation through these 3 amino acid substitutions is also adopted by other butterfly species (Boloria eunomia, Aglais urticae, Colias erate, and Polycaena lua) concurrent with M. cinxia in the Tianshan Mountains of China, i.e., convergent evolution in butterflies.


Assuntos
Borboletas , Fritillaria , Animais , Borboletas/genética , Borboletas/metabolismo , Glucose-6-Fosfato Isomerase/genética , Glucose-6-Fosfato Isomerase/metabolismo , Substituição de Aminoácidos , Temperatura
18.
ACS Nano ; 16(9): 15215-15225, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36048506

RESUMO

Metallic group VIB transition metal dichalcogenides (1T-TMDs) have attracted great interest because of their outstanding performance in electrocatalysis, supercapacitors, batteries, and so on, whereas the strict fabrication conditions and thermodynamical metastability of 1T-TMDs greatly restrict their extensive applications. Therefore, it is significant to obtain stable and high-concentration 1T-TMDs in a simple and large-scale strategy. Herein, we report a facile and large-scale synthesis of high-concentration 1T-TMDs via an ionic liquid (IL) assisted hydrothermal strategy, including 1T-MoS2 (the obtained MoS2 sample was denoted as MoS2-IL), 1T-WS2, 1T-MoSe2, and 1T-WSe2. More importantly, we found that IL can adsorb on the surface of 1T-MoS2, where the steric hindrance, π-π stacking, and hydrogen bonds of ionic liquid collectively induce the formation of the 1T-MoS2. In addition, DFT calculation reveals that electrons are transferred from [BMIM]SCN (1-butyl-3-methylimidazolium thiocyanate) to 1T-MoS2 layers by hydrogen bonds, which enhances the stability of 1T-MoS2, so the MoS2-IL performs with high stability for 180 days at room temperature without obvious change. Furthermore, the MoS2-IL exhibits excellent HER performance with an overpotential of 196 mV at 10 mA cm-2 in acid conditions.

19.
J Org Chem ; 87(19): 13367-13374, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36075004

RESUMO

The use of 2-carboxyphenylboronic acid (5 mol %) and oxalic acid (10 mol %) with 2-butanone as a solvent for the racemization of a range of enantiomerically pure secondary and tertiary alcohols is demonstrated. The process is postulated to proceed via reversible Brønsted acid-catalyzed C-O bond cleavage through an achiral carbocation intermediate.

20.
World J Surg Oncol ; 20(1): 304, 2022 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-36138439

RESUMO

BACKGROUND: Tumor deposits (TDs) have been identified as an independent prognostic factor in gastric cancer (GC). However, the associated clinicopathological factors and how to simply and reasonably incorporate TD into the TNM staging system remain undetermined. The aim of the current study was therefore to assess the significance of TD among radically resected GC patients. METHODS: We retrospectively reviewed 1915 patients undergoing radical resection between 2007 and 2012. The patients were classified into two groups according to TD status (absent vs. present), and the clinicopathologic characteristics, DFS, and OS were compared. Associations of TD presence with other clinicopathologic factors were evaluated by logistic regression analysis. Univariate and multivariate Cox regression analyses were performed to determine the prognostic factors for DFS and OS in the primary cohort. Propensity score matching (PSM) was performed to reduce the possibility of selection bias according to the presence of TD. External validation of previously proposed modified staging systems incorporating TD was conducted. RESULTS: The detection rate of TD was 10.5% (201/1915). The presence of TD was significantly related to unfavorable clinicopathologic variables, including advanced T and N categories. According to the multivariate Cox regression analysis, the presence of TD was identified as an independent prognostic factor for DFS and OS in the primary cohort (both P < 0.001). In the after-PSM cohort, TD presence also significantly shortened DFS and OS. In the external validation, one system that incorporated TD into the pTNM stage had the best performance. CONCLUSIONS: The presence of TD was significantly associated with poor survival in radically resected GC patients. The incorporation of TD into the TNM staging system can further improve the predictive capability. A multicenter cohort with a large sample size is needed to determine the appropriate method of incorporation.


Assuntos
Neoplasias Gástricas , China/epidemiologia , Extensão Extranodal , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/patologia
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