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1.
Int J Infect Dis ; : 107045, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38604470

RESUMO

BACKGROUND: The course of organ dysfunction (OD) in Corona Virus Disease 2019 (COVID-19) patients is unknown. Herein, we analyse the temporal patterns of OD in intensive care unit-admitted COVID-19 patients. METHODS: Sequential organ failure assessment scores were evaluated daily within 2 weeks of admission to determine the temporal trajectory of OD using group-based multitrajectory modelling (GBMTM). RESULTS: 392 patients were enrolled with a 28-day mortality rate of 53.6%. GBMTM identified four distinct trajectories. Group 1 (mild OD, n=64), with a median APACHE II score of 13 (IQR 9-21), had an early resolution of OD and a low mortality rate. Group 2 (moderate OD, n=140), with a median APACHE II score of 18 (IQR 13-22), had a 28-day mortality rate of 30.0%. Group 3 (severe OD, n=117), with a median APACHR II score of 20 (IQR 13-27), had a deterioration trend of respiratory dysfunction and a 28-day mortality rate of 69.2%. Group 4 (extremely severe OD, n=71), with a median APACHE II score of 20 (IQR 17-27), had a significant and sustained OD affecting all organ systems and a 28-day mortality rate of 97.2%. CONCLUSIONS: Four distinct trajectories of OD were identified, and respiratory dysfunction trajectory could predict nonpulmonary OD trajectories and patient prognosis.

2.
Cancer Biomark ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38517776

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is a prevalent form of malignancy globally. Disulfidptosis is novel programmed cell death pathway based on disulfide proteins, may have a positive impact on the development of LUAD treatment strategies. OBJECTIVE: To investigate the impact of disulfidptosis-related genes (DRGs) on the prognosis of LUAD, developed a risk model to facilitate the diagnosis and prognostication of patients. We also explored ACTN4 (DRGs) as a new therapeutic biomarker for LUAD. METHODS: We investigated the expression patterns of DRGs in both LUAD and noncancerous tissues. To assess the prognostic value of the DRGs, we developed risk models through univariate Cox analysis and lasso regression. The expression and function of ACTN4 was evaluated by qRT-PCR, immunohistochemistry and in vitro experiments. The TIMER examined the association between ACTN4 expression and immune infiltration in LUAD. RESULTS: Ten differentially expressed DRGs were identified. And ACTN4 was identified as potential risk factors through univariate Cox regression analysis (P< 0.05). ACTN4 expression and riskscore were used to construct a risk model to predict overall survival in LUAD, and high-risk demonstrated a significantly higher mortality rate compared to the low-risk cohort. qRT-PCR and immunohistochemistry assays indicated ACTN4 was upregulated in LUAD, and the upregulation was associated with clinicopathologic features. In vitro experiments showed the knockdown of ACTN4 expression inhibited the proliferation in LUAD cells. The TIMER analysis demonstrated a correlation between the expression of ACTN4 and the infiltration of diverse immune cells. Elevated ACTN4 expression was associated with a reduction in memory B cell count. Additionally, the ACTN4 expression was associated with m6A modification genes. CONCLUSIONS: Our study introduced a prognostic model based on DRGs, which could forecast the prognosis of patients with LUAD. The biomarker ACTN4 exhibits promise for the diagnosis and management of LUAD, given its correlation with tumor immune infiltration and m6A modification.

3.
Psychol Health Med ; : 1-19, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38503424

RESUMO

Suicide among college students is a challenging problem globally. Yet, the association between sleep quality, depressive symptoms, and suicidal ideation remains unclear. This study aims to understand if depressive symptoms mediate the relationship between sleep quality and suicide ideation and whether the interaction between depressive symptoms and sleep quality on suicidal ideation is additive. A total of 1182 college students were recruited, and sleep quality, depressive symptoms, and suicidal ideation were assessed using questionnaires. Univariate analysis, logistic regression analysis, linear regression models, and the Sobel test were performed. The results showed that, among college students, poor sleep quality was positively associated with suicidal ideation, and the association was mediated through depressive symptoms. Moreover, there was a significant additive interaction between poor sleep quality and depressive symptoms on suicidal ideation. These findings suggest that, in the process of preventing and treating suicidal ideation in college students with sleep disorders, we should focus on the evaluation and intervention of depressive symptoms and adopt multidisciplinary team interventions for college students with sleep disorders and depression.

4.
Med Res Rev ; 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515232

RESUMO

Atropisomerism, an expression of axial chirality caused by limited bond rotation, is a prominent aspect within the field of medicinal chemistry. It has been shown that atropisomers of a wide range of compounds, including established FDA-approved drugs and experimental molecules, display markedly different biological activities. The time-dependent reversal of chirality in atropisomers poses complexity and obstacles in the process of drug discovery and development. Nonetheless, recent progress in understanding atropisomerism and enhanced characterization methods have greatly assisted medicinal chemists in the effective development of atropisomeric drug molecules. This article provides a comprehensive review of their special design thoughts, synthetic routes, and biological activities, serving as a reference for the synthesis and biological evaluation of bioactive atropisomers in the future.

5.
Adv Mater ; : e2308550, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38478729

RESUMO

The development of ultrathin, stable ferroelectric materials is crucial for advancing high-density, low-power electronic devices. Nonetheless, ultrathin ferroelectric materials are rare due to the critical size effect. Here, a novel ferroelectric material, magnesium molybdenum oxide (Mg2 Mo3 O8 ) is presented. High-quality ultrathin Mg2 Mo3 O8 crystals are synthesized using chemical vapor deposition (CVD). Ultrathin Mg2 Mo3 O8 has a wide bandgap (≈4.4 eV) and nonlinear optical response. Mg2 Mo3 O8 crystals of varying thicknesses exhibit out-of-plane ferroelectric properties at room temperature, with ferroelectricity retained even at a 2 nm thickness. The Mg2 Mo3 O8 exhibits a relatively large remanent polarization ranging from 33 to 52 µC cm- 2 , which is tunable by changing its thickness. Notably, Mg2 Mo3 O8 possesses a high Curie temperature (>980 °C) across various thicknesses. Moreover, the as-grown Mg2 Mo3 O8 crystals display remarkable stability under harsh environments. This work introduces nolanites-type crystal into ultrathin ferroelectrics. The scalable synthesis of stable ultrathin ferroelectric Mg2 Mo3 O8 expands the scope of ferroelectric materials and may prosper applications of ferroelectrics.

6.
Front Genet ; 15: 1363896, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444760

RESUMO

Introduction: As the evaluation indices, cancer grading and subtyping have diverse clinical, pathological, and molecular characteristics with prognostic and therapeutic implications. Although researchers have begun to study cancer differentiation and subtype prediction, most of relevant methods are based on traditional machine learning and rely on single omics data. It is necessary to explore a deep learning algorithm that integrates multi-omics data to achieve classification prediction of cancer differentiation and subtypes. Methods: This paper proposes a multi-omics data fusion algorithm based on a multi-view graph neural network (MVGNN) for predicting cancer differentiation and subtype classification. The model framework consists of a graph convolutional network (GCN) module for learning features from different omics data and an attention module for integrating multi-omics data. Three different types of omics data are used. For each type of omics data, feature selection is performed using methods such as the chi-square test and minimum redundancy maximum relevance (mRMR). Weighted patient similarity networks are constructed based on the selected omics features, and GCN is trained using omics features and corresponding similarity networks. Finally, an attention module integrates different types of omics features and performs the final cancer classification prediction. Results: To validate the cancer classification predictive performance of the MVGNN model, we conducted experimental comparisons with traditional machine learning models and currently popular methods based on integrating multi-omics data using 5-fold cross-validation. Additionally, we performed comparative experiments on cancer differentiation and its subtypes based on single omics data, two omics data, and three omics data. Discussion: This paper proposed the MVGNN model and it performed well in cancer classification prediction based on multiple omics data.

7.
Int J Mol Sci ; 25(4)2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38396956

RESUMO

Ramshorn snails from the family Planorbidae are important freshwater snails due to their low trophic level, and some of them act as intermediate hosts for zoonotic trematodes. There are about 250 species from 40 genera of Planorbidae, but only 14 species from 5 genera (Anisus, Biomphalaria, Bulinus, Gyraulus, and Planorbella) have sequenced complete mitochondrial genomes (mitogenomes). In this study, we sequenced and assembled a high-quality mitogenome of a ramshorn snail, Polypylis sp. TS-2018, which represented the first mitogenome of the genus. The mitogenome of Polypylis sp. TS-2018 is 13,749 bp in length, which is shorter than that of most gastropods. It contains 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, and 2 ribosomal RNA (rRNA). We compared mitogenome characteristics, selection pressure, and gene rearrangement among all of the available mitogenomes of ramshorn snails. We found that the nonsynonymous and synonymous substitution rates (Ka/Ks) of most PCGs indicated purifying and negative selection, except for atp8 of Anisus, Biomphalaria, and Gyraulus, which indicated positive selection. We observed that transpositions and reverse transpositions occurred on 10 tRNAs and rrnS, which resulted in six gene arrangement types. We reconstructed the phylogenetic trees using the sequences of PCGs and rRNAs and strongly supported the monophyly of each genus, as well as three tribes in Planorbidae. Both the gene rearrangement and phylogenetic results suggested that Polypylis had a close relationship with Anisus and Gyraulus, while Bulinus was the sister group to all of the other genera. Our results provide useful data for further investigation of species identification, population genetics, and phylogenetics among ramshorn snails.


Assuntos
Acanthaceae , Genoma Mitocondrial , Animais , Filogenia , Genoma Mitocondrial/genética , Caramujos/genética , RNA Ribossômico/genética , RNA de Transferência/genética
8.
J Am Chem Soc ; 146(6): 3764-3772, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38304977

RESUMO

TiO2-supported Pt species have been widely applied in numerous critical reactions involving photo-, thermo-, and electrochemical-catalysis for decades. Manipulation of the state of the Pt species in Pt/TiO2 catalysts is crucial for fine-tuning their catalytic performance. Here, we report an interesting discovery showing the epitaxial growth of PtO2 atomic layers on rutile TiO2, potentially allowing control of the states of active Pt species in Pt/TiO2 catalysts. The presence of PtO2 atomic layers could modulate the geometric configuration and electronic state of the Pt species under reduction conditions, resulting in a spread of the particle shape and obtaining a Pt/PtO2/TiO2 structure with more positive valence of Pt species. As a result, such a catalyst exhibits exceptional electrocatalytic activity and stability toward hydrogen evolution reaction, while also promoting the thermocatalytic CO oxidation, surpassing the performance of the Pt/TiO2 catalyst with no epitaxial structure. This novel epitaxial growth of the PtO2 structure on rutile TiO2 in Pt/TiO2 catalysts shows its potential in the rational design of highly active and economical catalysts toward diverse catalytic reactions.

9.
Sci Rep ; 14(1): 3934, 2024 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365831

RESUMO

Novel methods are required to enhance lung cancer detection, which has overtaken other cancer-related causes of death as the major cause of cancer-related mortality. Radiologists have long-standing methods for locating lung nodules in patients with lung cancer, such as computed tomography (CT) scans. Radiologists must manually review a significant amount of CT scan pictures, which makes the process time-consuming and prone to human error. Computer-aided diagnosis (CAD) systems have been created to help radiologists with their evaluations in order to overcome these difficulties. These systems make use of cutting-edge deep learning architectures. These CAD systems are designed to improve lung nodule diagnosis efficiency and accuracy. In this study, a bespoke convolutional neural network (CNN) with a dual attention mechanism was created, which was especially crafted to concentrate on the most important elements in images of lung nodules. The CNN model extracts informative features from the images, while the attention module incorporates both channel attention and spatial attention mechanisms to selectively highlight significant features. After the attention module, global average pooling is applied to summarize the spatial information. To evaluate the performance of the proposed model, extensive experiments were conducted using benchmark dataset of lung nodules. The results of these experiments demonstrated that our model surpasses recent models and achieves state-of-the-art accuracy in lung nodule detection and classification tasks.


Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Humanos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Redes Neurais de Computação , Pulmão/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos
10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(1): 190-197, 2024 Jan 20.
Artigo em Chinês | MEDLINE | ID: mdl-38322514

RESUMO

Objective: To create a novel chitosan antibacterial hemostatic sponge (NCAHS) and to evaluate its material and biological properties. Methods: Chitosan, a polysaccharide, was used as the sponge substrate and different proportions of sodium tripolyphosphate (STPP), glycerol, and phenol sulfonyl ethylamine were added to prepare the sponges through the freeze-drying method. The whole-blood coagulation index (BCI) was used as the screening criterion to determine the optimal concentrations of chitosan and the other additives and the hemostatic sponges were prepared accordingly. Zein/calcium carbonate (Zein/CaCO3) composite microspheres loaded with ciprofloxacin hydrochloride were prepared and added to the hemostatic sponges to obtain NCAHS. Scanning electron microscope was used to observe the microscopic morphology and porosity of the NCAHS. The water absorption rate, in vitro antibacterial susceptibility rate against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), in vitro coagulation performance, and hemocompatibility of NCAHS were examined. The coagulation performance of NCAHS was evaluated by using rabbit liver injury and rabbit auricular artery hemorrhageear models and commercial hemostatic sponge (CHS) was used as a control. The in vivo biocompatibility, including such aspects as cytotoxicity, skin irritation in animals, and acute in vivo toxicity, of the NCAHS extracts was examined by using as a reference the national standards for biological evaluation of medical devices. Results: The NCAHS prepared with 1.5% chitosan (W/V), 0.01% STPP (W/V), 0% glycerol (V/V), 0.15% phenol-sulfonyl-ethylamine (V/V), Zein and CaCO3 at the mixing ratio of 5∶1 (W/W), Zein at the final mass concentration of 2.5 g/L, and ethanol at the final concentration of 17.5% (V/V) were fine and homogeneous, possessing a honeycomb-like porous structure with a pore size of about 200 µm. The NCAHS thus prepared had the lowest BCI value. The water absorption ([2362.16±201.15] % vs. [1102.56±91.79]%) and in vitro coagulation performance (31.338% vs. 1.591%) of NCAHS were significantly better than those of CHS (P<0.01). Tests with the in vivo auricular artery hemorrhage model ([36.00±13.42] s vs. [80.00±17.32] s) and rabbit liver bleeding model ([30.00±0] s vs. [70.00±17.32] s) showed that the hemostasis time of NCAHS was significantly shorter than that of CHS (P<0.01). NCAHS had significant inhibitory ability against S. aureus and E. coli. In addition, NCAHS showed good in vitro and in vivo biocompatibility. Conclusion: NCAHS is a composite sponge that shows excellent antimicrobial properties, hemostatic effect, and biocompatibility. Therefore, its extensive application in clinical settings is warranted.


Assuntos
Quitosana , Hemostáticos , Zeína , Animais , Coelhos , Quitosana/química , Hemostáticos/farmacologia , Escherichia coli , Glicerol/farmacologia , Staphylococcus aureus , Zeína/farmacologia , Hemostasia , Antibacterianos/farmacologia , Hemorragia , Água/farmacologia , Etilaminas/farmacologia , Fenóis/farmacologia
11.
Eur J Pharmacol ; 967: 176395, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38350592

RESUMO

Cardiac fibrosis, the hallmark of cardiovascular disease, is characterized by excessive deposition of extracellular matrix in the heart. Emerging evidence indicates that cardiac fibroblasts (CFs) play pivotal roles in driving cardiac fibrosis. However, due to incomplete insights into CFs, there are limited effective approaches to prevent or reverse cardiac fibrosis currently. Palmatine, a protoberberine alkaloid extracted from traditional Chinese botanical remedies, possesses diverse biological effects. This study investigated the potential therapeutic value and mechanism of palmatine against cardiac fibrosis. Adult male C57BL/6 mice were treated with vehicle, isoproterenol (ISO), or ISO plus palmatine for one week. After echocardiography assessment, mice hearts were collected for histopathology, real-time polymerase chain reaction, and Western blot analyses. Primary rat CFs were utilized in vitro. Compared to control, ISO-treated mice exhibited cardiac hypertrophy and structural abnormalities; however, treatment with palmatine ameliorated these effects of ISO. Moreover, palmatine treatment mitigated ISO-induced cardiac fibrosis. Network pharmacology and molecular docking analysis showed that palmatine strongly binds the regulators of cardiac fibrosis including signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin. Furthermore, palmatine reduced the elevated fibrotic factor expressions and overactivated STAT3 induced by ISO, Transformed growth factor ß1 (TGF-ß1), or interleukin-6 both in vivo and in vitro. Additionally, blocking STAT3 suppressed the TGF-ß1-induced CF activation. Collectively, these data demonstrated that palmatine attenuated cardiac fibrosis partly by inhibiting fibroblast activation through the STAT3 pathway. This provides an experimental basis for the clinical treatment of cardiac fibrosis with palmatine.


Assuntos
Alcaloides de Berberina , Cardiomiopatias , Fator de Crescimento Transformador beta1 , Ratos , Masculino , Animais , Camundongos , Fator de Crescimento Transformador beta1/metabolismo , Fator de Transcrição STAT3/metabolismo , Simulação de Acoplamento Molecular , Camundongos Endogâmicos C57BL , Cardiomiopatias/metabolismo , Isoproterenol/farmacologia , Fibroblastos , Fibrose , Miocárdio/metabolismo , Mamíferos
12.
Cell Rep Med ; 5(2): 101382, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38237596

RESUMO

The prevalence of heart failure (HF) subtypes, which are classified by left ventricular ejection fraction (LVEF), demonstrate significant sex differences. Here, we perform sex-stratified genome-wide association studies (GWASs) on LVEF and transcriptome-wide Mendelian randomization (MR) on LVEF, all-cause HF, HF with reduced ejection fraction (HFrEF), and HF with preserved ejection fraction (HFpEF). The sex-stratified GWASs of LVEF identified three sex-specific loci that were exclusively detected in the sex-stratified GWASs. Three drug target genes show sex-differential effects on HF/HFrEF via influencing LVEF, with NPR2 as the target gene for the HF drug Cenderitide under phase 2 clinical trial. Our study highlights the importance of considering sex-differential genetic effects in sex-balanced diseases such as HF and emphasizes the value of sex-stratified GWASs and MR in identifying putative genetic variants, causal genes, and candidate drug targets for HF, which is not identifiable using a sex-combined strategy.


Assuntos
Insuficiência Cardíaca , Humanos , Masculino , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/genética , Função Ventricular Esquerda , Volume Sistólico , Estudo de Associação Genômica Ampla , Prognóstico , Análise da Randomização Mendeliana , Transcriptoma/genética
13.
Nat Commun ; 15(1): 693, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38267445

RESUMO

Ferroelectric tunnel junctions are promising towards high-reliability and low-power non-volatile memories and computing devices. Yet it is challenging to maintain a high tunnelling electroresistance when the ferroelectric layer is thinned down towards atomic scale because of the ferroelectric structural instability and large depolarization field. Here we report ferroelectric tunnel junctions based on samarium-substituted layered bismuth oxide, which can maintain tunnelling electroresistance of 7 × 105 with the samarium-substituted bismuth oxide film down to one nanometer, three orders of magnitude higher than previous reports with such thickness, owing to efficient barrier modulation by the large ferroelectric polarization. These ferroelectric tunnel junctions demonstrate up to 32 resistance states without any write-verify technique, high endurance (over 5 × 109), high linearity of conductance modulation, and long retention time (10 years). Furthermore, tunnelling electroresistance over 109 is achieved in ferroelectric tunnel junctions with 4.6-nanometer samarium-substituted bismuth oxide layer, which is higher than commercial flash memories. The results show high potential towards multi-level and reliable non-volatile memories.

14.
Mol Oncol ; 18(1): 170-189, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37867415

RESUMO

Endoribonuclease DICER is an RNase III enzyme that mainly processes microRNAs in the cytoplasm but also participates in nuclear functions such as chromatin remodelling, epigenetic modification and DNA damage repair. The expression of nuclear DICER is low in most human cancers, suggesting a tight regulation mechanism that is not well understood. Here, we found that ubiquitin carboxyl-terminal hydrolase 7 (USP7), a deubiquitinase, bounded to DICER and reduced its nuclear protein level by promoting its ubiquitination and degradation through MDM2, a newly identified E3 ubiquitin-protein ligase for DICER. This USP7-MDM2-DICER axis impaired histone γ-H2AX signalling and the recruitment of DNA damage response (DDR) factors, possibly by influencing the processing of small DDR noncoding RNAs. We also showed that this negative regulation of DICER by USP7 via MDM2 was relevant to human tumours using cellular and clinical data. Our findings revealed a new way to understand the role of DICER in malignant tumour development and may offer new insights into the diagnosis, treatment and prognosis of cancers.


Assuntos
Neoplasias , Ribonuclease III , Humanos , Dano ao DNA , Reparo do DNA , Neoplasias/genética , Neoplasias/tratamento farmacológico , Proteínas Nucleares/genética , Ribonuclease III/genética , Ribonuclease III/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Peptidase 7 Específica de Ubiquitina/genética , Peptidase 7 Específica de Ubiquitina/metabolismo , Ubiquitinação
15.
Appl Health Econ Health Policy ; 22(1): 85-95, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37910314

RESUMO

OBJECTIVE: To assess the cost effectiveness of the second COVID-19 booster vaccination with different age groups. METHODS: We developed a decision-analytic Susceptible-Exposed-Infected-Recovered (SEIR)-Markov model by five age groups (0-4 years, 5-11 years 12-17 years, 18-49 years, and 50+ years) and calibrated the model by actual mortality in each age group in the USA. We conducted five scenarios to evaluate the cost effectiveness of the second booster strategy and incremental benefits if the strategy would expand to 18-49 years and 12-17 years, from a health care system perspective. The analysis was reported according to the Consolidated Health Economic Evaluation Reporting Standards 2022 statement. RESULTS: Implementing the second booster strategy for those aged ≥ 50 years cost $823 million but reduced direct medical costs by $1166 million, corresponding to a benefit-cost ratio of 1.42. Moreover, the strategy also resulted in a gain of 2596 quality-adjusted life-years (QALYs) during the 180-day evaluation period, indicating it was dominant. Further, vaccinating individuals aged 18-49 years with the second booster would result in an additional gain of $1592 million and 8790 QALYs. Similarly, expanding the vaccination to individuals aged 12-17 years would result in an additional gain of $16 million and 403 QALYs. However, if social interaction between all age groups was severed, vaccination expansion to ages 18-49 and 12-17 years would no longer be dominant but cost effective with an incremental cost-effectiveness ratio (ICER) of $37,572 and $26,705/QALY gained, respectively. CONCLUSION: The second booster strategy was likely to be dominant in reducing the disease burden of the COVID-19 pandemic. Expanding the second booster strategy to ages 18-49 and 12-17 years would remain dominant due to their social contacts with the older age group.


Assuntos
COVID-19 , Análise de Custo-Efetividade , Humanos , Idoso , Análise Custo-Benefício , Pandemias , COVID-19/prevenção & controle , Vacinação , Anos de Vida Ajustados por Qualidade de Vida
16.
Angew Chem Int Ed Engl ; 63(5): e202312663, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38032817

RESUMO

Azomethine imines, as a prominent class of 1,3-dipolar species, hold great significance and potential in organic and medicinal chemistry. However, the reported synthesis of centrally chiral azomethine imines relies on kinetic resolution, and the construction of axially chiral azomethine imines remains unexplored. Herein, we present the synthesis of axially chiral azomethine imines through copper- or chiral phosphoric acid catalyzed ring-closure reactions of N'-(2-alkynylbenzylidene)hydrazides, showcasing high efficiency, mild conditions, broad substrate scope, and excellent enantioselectivity. Furthermore, the biological evaluation revealed that the synthesized axially chiral azomethine imines effectively protect dorsal root ganglia (DRG) neurons by inhibiting apoptosis induced by oxaliplatin, offering a promising therapeutic approach for chemotherapy-induced peripheral neuropathy (CIPN). Remarkably, the (S)- and (R)-atropisomers displayed distinct neuroprotective activities, underscoring the significance of axial stereochemistry.


Assuntos
Compostos Azo , Iminas , Tiossemicarbazonas , Estereoisomerismo , Compostos Azo/farmacologia , Catálise
17.
Cell Oncol (Dordr) ; 47(1): 37-54, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37642916

RESUMO

Lung cancer, being the most widespread and lethal form of cancer globally, has a high incidence and mortality rate primarily attributed to challenges associated with early detection, extensive metastasis, and frequent recurrence. In the context of lung cancer development, noncoding RNA molecules have a crucial role in governing gene expression and protein synthesis. Specifically, tRNA-derived fragments (tRFs), a subset of noncoding RNAs, exert significant biological influences on cancer progression, encompassing transcription and translation processes as well as epigenetic regulation. This article primarily examines the mechanisms by which tRFs modulate gene expression and contribute to tumorigenesis in lung cancer. Furthermore, we provide a comprehensive overview of the current bioinformatics analysis of tRFs in lung cancer, with the objective of offering a systematic and efficient approach for studying the expression profiling, functional enrichment, and molecular mechanisms of tRFs in this disease. Finally, we discuss the clinical significance and potential avenues for future research on tRFs in lung cancer. This paper presents a comprehensive systematic review of the existing research findings on tRFs in lung cancer, aiming to offer improved biomarkers and drug targets for clinical management of lung cancer.


Assuntos
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Epigênese Genética , RNA de Transferência/genética , RNA de Transferência/metabolismo , RNA não Traduzido , Regulação Neoplásica da Expressão Gênica
18.
Dev Comp Immunol ; 152: 105109, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38061436

RESUMO

Complement component 3d (C3d), the final cleavage product of complement component C3, interacts with CR2 and thus plays a crucial role in linking the innate and adaptive immune systems. Additionally, human C3d executes various functions in its dimeric form, which is more effective than its monomeric form. In this study, we aimed to explored whether chicken C3d (chC3d) exhibits similar characteristics, namely dimerization and binding of dimeric chC3d to chicken CR2 (chCR2). We investigated the interaction and co-localization of chC3d with itself using coimmunoprecipitation and confocal laser scanning microscopy, respectively. Then, dimeric chC3d was detected using native polyacrylamide gel electrophoresis and western blotting, and its equilibrium dissociation constant KD (827 nM) was determined using surface plasmon resonance. Finally, the interaction modes of dimeric chC3d were identified using molecular docking simulations, which revealed that dimeric chC3d could crosslink with chCR2 receptor. Overall, our findings will facilitate future explorations of the chicken complement system.


Assuntos
Complemento C3d , Receptores de Complemento 3d , Animais , Humanos , Receptores de Complemento 3d/química , Receptores de Complemento 3d/metabolismo , Galinhas , Simulação de Acoplamento Molecular , Fatores Imunológicos , Receptores de Complemento
19.
Histol Histopathol ; : 18682, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38059279

RESUMO

AIMS: To investigate the clinicopathological characteristics and potential diagnostic pitfalls of bronchiolar adenoma (BA) combined with lung adenocarcinoma (LUAD) in the same lesion. METHODS: We analyzed eight cases of BA combined with LUAD from our hospital pathology department between July 2020 and January 2022, and summarized their clinical data, radiological features, histopathological characteristics and immunohistochemical phenotypes. RESULTS: Upon macroscopic examination, the lesions were characterized by gray-white or gray-brown solid nodules with well-defined borders, measuring 0.6-1.8cm in maximum diameter. The incidence of proximal-type BA (6/8) was higher than that of distal-type BA (2/8), and they combined with different stages of LUAD, including adenocarcinoma in situ, minimally invasive adenocarcinoma, invasive adenocarcinoma, and invasive mucinous adenocarcinoma (IMA). Immunohistochemistry showed that cytokeratin 5/6 and P40 were positive in the continuous basal cell layer in BA, but only scattered positive basal cells were seen at the junction of BA and LUAD. TTF-1 was positive in proximal-type BA ciliated cells in five cases and in LUAD cells in seven cases, and weakly positive in some basal cells. One case of IMA and mucinous cells of BA were TTF-1 negative. There was partially positive Napsin-A expression in BA luminal cells and LUAD cells of all cases except IMA. CONCLUSION: There is no obvious boundary when BA and LUAD are in the same lesion. The luminal epithelial cells in the area where the two components migrate toward each other are atypical and lack a continuous underlying basal cell layer. Microscopic diagnosis should be aided by immunohistochemistry.

20.
Nanomaterials (Basel) ; 13(23)2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-38063704

RESUMO

Defects are an inevitable occurrence during the manufacturing and use of ferromagnetic materials, making it crucial to study the microscopic mechanism of magnetostrictive properties of ferromagnetic materials with defects. This paper conducts molecular dynamics simulations on low-dimensional iron thin films containing hole or crack defects, analyzes and compares the impact of defect size on magnetostrictive properties, and investigates the microscopic mechanism of their effects. The results indicate that the saturation magnetostrictive strains of the defect models do not increase monotonically as the defect size increases. Additionally, it is discovered that the arrangement of atomic magnetic moments in the initial magnetic moment configuration also affects the magnetostrictive properties. When controlling the size of the hole or crack within a certain defect area, it is found that the hole size has less influence on the initial magnetic moment configuration, resulting in a smaller corresponding change in the saturation strain and thus having a lesser impact on the magnetostrictive properties. Conversely, when the crack size changes, the arrangement of the atomic magnetic moments in the initial magnetic moment configuration changes more significantly, resulting in a greater corresponding change in saturation strain, and thus having a greater impact on the magnetostriction performance.

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