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1.
Acta Crystallogr E Crystallogr Commun ; 80(Pt 4): 347-350, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38584727

RESUMO

The title compound, C14H12N2O4, was obtained from 2-acetyl-6-amino-naphthalene through two-step reactions of acetyl-ation and nitration. The mol-ecule comprises the naphthalene ring system consisting of functional systems bearing a acetyl group (C-2), a nitro group (C-5), and an acetyl-amino group (C-6). In the crystal, the mol-ecules are assembled into two-dimensional sheet-like structures by inter-molecular N-H⋯O and C-H⋯O hydrogen-bonding inter-actions. Hirshfeld surface analysis illustrates that the most important contributions to the crystal packing are from O⋯H/H⋯O (43.7%), H⋯H (31.0%), and C⋯H/H⋯C (8.5%) contacts.

2.
Anesthesiology ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38558232

RESUMO

BACKGROUND: The relationship between postoperative adverse events and blood pressures in the preoperative period remains poorly understood. This study tested the hypothesis that day-of-surgery preoperative blood pressures are associated with postoperative adverse events. METHODS: We conducted a retrospective, observational study of adult patients having elective procedures requiring an inpatient stay between November 2017 and July 2021 at Vanderbilt University Medical Center to examine the independent associations between preoperative systolic and diastolic blood pressures (SBP, DBP) recorded immediately before anesthesia care and number of postoperative adverse events - myocardial injury, stroke, acute kidney injury (AKI), and mortality, while adjusting for potential confounders. We used multivariable ordinal logistic regression to model the relationship. RESULTS: The analysis included 57,389 cases. The overall incidence of myocardial injury, stroke, AKI, and mortality within 30 days of surgery was 3.4% (1,967 events), 0.4% (223), 10.2% (5,871), and 2.1% (1,223), respectively. The independent associations between both SBP and DBP measurements and number of postoperative adverse events were found to be U-shaped, with greater risk both above and below SBP 143 mmHg and DBP 86 mmHg - the troughs of the curves. The associations were strongest at SBP 173 mmHg (adjusted odds ratio [aOR] 1.212 versus 143 mmHg; 95% CI, 1.021 to 1.439; p = 0.028), SBP 93 mmHg (aOR 1.339 versus 143 mmHg; 95% CI, 1.211 to 1.479; p < 0.001), DBP 106 mmHg (aOR 1.294 versus 86 mmHg; 95% CI, 1.003 to 1.17671; p = 0.048), and DBP 46 mmHg (aOR 1.399 versus 86 mmHg; 95% CI, 1.244 to 1.558; p < 0.001). CONCLUSIONS: Preoperative blood pressures both below and above a specific threshold were independently associated with a higher number of postoperative adverse events, but the data do not support specific strategies for managing patients with low or high blood pressure on the day of surgery.

3.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1318-1326, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621979

RESUMO

In order to study the neuroprotective mechanism of cinnamaldehyde on reserpine-induced Parkinson's disease(PD) rat models, 72 male Wistar rats were randomly divided into blank group, model group, Madopar group, and cinnamaldehyde high-, medium-, and low-dose groups. Except for the blank group, the other groups were intraperitoneally injected with reserpine of 0.1 mg·kg~(-1) once every other morning, and cinnamaldehyde and Madopar solutions were gavaged every afternoon. Open field test, rotarod test, and oral chewing movement evaluation were carried out in the experiment. The brain was taken and fixed. The positive expression of dopamine receptor D1(DRD1) was detected by TSA, and the changes in neurotransmitters such as dopamine(DA) and 3,4-dihydroxyphenylacetic acid(DOPAC) in the brain were detected by enzyme-linked immunosorbent assay(ELISA). The protein and mRNA expression levels of tyrosine hydroxylase(TH) and α-synuclein(α-Syn) in substantia nigra(SN) were detected by RT-PCR and Western blot. The results showed that after the injection of reserpine, the hair color of the model group became yellow and dirty; the arrest behavior was weakened, and the body weight was reduced. The spontaneous movement and exploration behavior were reduced, and the coordination exercise ability was decreased. The number of oral chewing was increased, but the cognitive ability was decreased, and the proportion of DRD1 positive expression area in SN was decreased. The expression of TH protein and mRNA was down-regulated, and that of α-Syn protein and mRNA was up-regulated. After cinnamaldehyde intervention, it had an obvious curative effect on PD model animals. The spontaneous movement behavior, the time of staying in the rod, the time of movement, the distance of movement, and the number of standing times increased, and the number of oral chewing decreased. The proportion of DRD1 positive expression area in SN increased, and the protein and mRNA expression levels of α-Syn were down-regulated. The protein and mRNA expression levels of TH were up-regulated. In addition, the levels of DA, DOPAC, and homovanillic acid(HVA) neurotransmitters in the brain were up-regulated. This study can provide a new experimental basis for clinical treatment and prevention of PD.


Assuntos
Acroleína/análogos & derivados , Doença de Parkinson , Ratos , Masculino , Animais , Doença de Parkinson/etiologia , Doença de Parkinson/genética , Reserpina/efeitos adversos , Reserpina/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Ratos Wistar , Substância Negra/metabolismo , RNA Mensageiro/metabolismo , Neurotransmissores/metabolismo , Tirosina 3-Mono-Oxigenase/genética , Tirosina 3-Mono-Oxigenase/metabolismo
4.
Cancer Lett ; : 216882, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38636893

RESUMO

Super enhancers (SEs) are genomic regions comprising multiple closely spaced enhancers, typically occupied by a high density of cell-type-specific master transcription factors (TFs) and frequently enriched in key oncogenes in various tumors, including neuroblastoma (NB), one of the most prevalent malignant solid tumors in children originating from the neural crest. Cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) is a newly identified super-enhancer-driven gene regulated by master TFs in NB; however, its function in NB remains unclear. Through an integrated study of publicly available datasets and microarrays, we observed a significantly elevated CDK5RAP3 expression level in NB, associated with poor patient prognosis. Further research demonstrated that CDK5RAP3 promotes the growth of NB cells, both in vitro and in vivo. Mechanistically, defective CDK5RAP3 interfered with the UFMylation system, thereby triggering endoplasmic reticulum (ER) phagy. Additionally, we provide evidence that CDK5RAP3 maintains the stability of MEIS2, a master TF in NB, and in turn, contributes to the high expression of CDK5RAP3. Overall, our findings shed light on the molecular mechanisms by which CDK5RAP3 promotes tumor progression and suggest that its inhibition may represent a novel therapeutic strategy for NB.

5.
Chem Commun (Camb) ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38616724

RESUMO

In this study, a novel electrocatalyst, namely Cu/N-pg-C derived from Cu-doped ZIF-8, was investigated for making syngas products with various H2/CO ratios. Different ratios of the electrocatalytic syngas products CO and H2 could be selected by adjusting the applied potential and hence tuning the transfer of electrons from N-doped graphitic carbon to the well-dispersed Cu nanoclusters.

6.
HGG Adv ; 5(3): 100290, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582968

RESUMO

Mendelian randomization (MR) is an instrumental variable approach used to infer causal relationships between exposures and outcomes, which is becoming increasingly popular because of its ability to handle summary statistics from genome-wide association studies. However, existing MR approaches often suffer the bias from weak instrumental variables, horizontal pleiotropy and sample overlap. We introduce MRBEE (MR using bias-corrected estimating equation), a multivariable MR method capable of simultaneously removing weak instrument and sample overlap bias and identifying horizontal pleiotropy. Our extensive simulations and real data analyses reveal that MRBEE provides nearly unbiased estimates of causal effects, well-controlled type I error rates and higher power than comparably robust methods and is computationally efficient. Our real data analyses result in consistent causal effect estimates and offer valuable guidance for conducting multivariable MR studies, elucidating the roles of pleiotropy, and identifying total 42 horizontal pleiotropic loci missed previously that are associated with myopia, schizophrenia, and coronary artery disease.

7.
Compr Rev Food Sci Food Saf ; 23(3): e13338, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38629461

RESUMO

Mycotoxins, ubiquitous contaminants in food, present a global threat to human health and well-being. Mitigation efforts, such as the implementation of sound agricultural practices, thorough food processing, and the advancement of mycotoxin control technologies, have been instrumental in reducing mycotoxin exposure and associated toxicity. To comprehensively assess mycotoxins and their toxicodynamic implications, the deployment of effective and predictive strategies is imperative. Understanding the manner of action, transformation, and cumulative toxic effects of mycotoxins, moreover, their interactions with food matrices can be gleaned through gene expression and transcriptome analyses at cellular and molecular levels. MicroRNAs (miRNAs) govern the expression of target genes and enzymes that play pivotal roles in physiological, pathological, and toxicological responses, whereas acute phase proteins (APPs) exert regulatory control over the metabolism of therapeutic agents, both endogenously and posttranscriptionally. Consequently, this review aims to consolidate current knowledge concerning the regulatory role of miRNAs in the initiation of toxicological pathways by mycotoxins and explores the potential of APPs as biomarkers following mycotoxin exposure. The findings of this research highlight the potential utility of miRNAs and APPs as indicators for the detection and management of mycotoxins in food through biological processes. These markers offer promising avenues for enhancing the safety and quality of food products.


Assuntos
MicroRNAs , Micotoxinas , Humanos , Micotoxinas/análise , MicroRNAs/genética , Contaminação de Alimentos/análise , Proteínas de Fase Aguda
8.
Microsyst Nanoeng ; 10: 54, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38654844

RESUMO

In implantable electrophysiological recording systems, the headstage typically comprises neural probes that interface with brain tissue and integrated circuit chips for signal processing. While advancements in MEMS and CMOS technology have significantly improved these components, their interconnection still relies on conventional printed circuit boards and sophisticated adapters. This conventional approach adds considerable weight and volume to the package, especially for high channel count systems. To address this issue, we developed a through-polymer via (TPV) method inspired by the through-silicon via (TSV) technique in advanced three-dimensional packaging. This innovation enables the vertical integration of flexible probes, amplifier chips, and PCBs, realizing a flexible, lightweight, and integrated device (FLID). The total weight of the FLIDis only 25% that of its conventional counterparts relying on adapters, which significantly increased the activity levels of animals wearing the FLIDs to nearly match the levels of control animals without implants. Furthermore, by incorporating a platinum-iridium alloy as the top layer material for electrical contact, the FLID realizes exceptional electrical performance, enabling in vivo measurements of both local field potentials and individual neuron action potentials. These findings showcase the potential of FLIDs in scaling up implantable neural recording systems and mark a significant advancement in the field of neurotechnology.

9.
Vasc Endovascular Surg ; : 15385744241249293, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649827

RESUMO

OBJECTIVES: Non-A non-B aortic dissection (AD) is a rare and life-threatening medical emergency, and it has been controversial whether it should be managed as type B aortic dissection (TBAD). The study aims to compare in-hospital and follow-up outcomes between patients with non-A non-B AD and those with TBAD treated by endovascular based treatment (EBT). METHODS: From January 2017 to December 2021, 96 consecutive patients with non-A non-B AD met the inclusion criteria and underwent EBT. Patients with TBAD were matched to patients with non-A non-B AD at a 1:1 ratio using propensity score matching analysis to correct for baseline confounding factors. The primary endpoint was all-cause mortality. Aortic-related events were defined as dissection-related death, aortic rupture, retrograde type A aortic dissection, reintervention, and type Ia endoleak. RESULTS: Patients with non-A non-B AD required more TEVAR-related adjunctive procedures compared to TBAD patients during EBT and they required a longer ICU length of stay (36.0 vs 24.0 hours, P < .05) as well as a longer hospitalization (8.0 vs 7.0 days, P < .05) after EBT. There was no statistical difference in overall survival after EBT for patients with TBAD and non-A non-B AD. However, compared to patients with TBAD, non-A non-B AD patients had a higher rate of reintervention and experienced more aortic-related late events during follow-up. CONCLUSION: Patients with non-A non-B acute AD who are treated with EBT do not have higher in-hospital or follow-up mortality rates compared to patients with type B AD. However, there is an increased risk of reintervention and aortic-related late events after the intervention during follow-up.

10.
Cell Death Discov ; 10(1): 186, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649363

RESUMO

Neuroblastoma (NB) is a common childhood tumor with a high incidence worldwide. The regulatory role of RNA N6-methyladenosine (m6A) in gene expression has attracted significant attention, and the impact of methyltransferase-like 14 (METTL14) on tumor progression has been extensively studied in various types of cancer. However, the specific influence of METTL14 on NB remains unexplored. Using data from the Target database, our study revealed significant upregulation of METTL14 expression in high-risk NB patients, with strong correlation with poor prognosis. Furthermore, we identified ETS1 and YY1 as upstream regulators that control the expression of METTL14. In vitro experiments involving the knockdown of METTL14 in NB cells demonstrated significant inhibition of cell proliferation, migration, and invasion. In addition, suppressing METTL14 inhibited NB tumorigenesis in nude mouse models. Through MeRIP-seq and RNA-seq analyses, we further discovered that YWHAH is a downstream target gene of METTL14. Mechanistically, we observed that methylated YWHAH transcripts, particularly those in the 5' UTR, were specifically recognized by the m6A "reader" protein YTHDF1, leading to the degradation of YWHAH mRNA. Moreover, the downregulation of YWHAH expression activated the PI3K/AKT signaling pathway, promoting NB cell activity. Overall, our study provides valuable insights into the oncogenic effects of METTL14 in NB cells, highlighting its role in inhibiting YWHAH expression through an m6A-YTHDF1-dependent mechanism. These findings also suggest the potential utility of a biomarker panel for prognostic prediction in NB patients.

11.
Nat Commun ; 15(1): 3385, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649715

RESUMO

There is a long-standing debate about the magnitude of the contribution of gene-environment interactions to phenotypic variations of complex traits owing to the low statistical power and few reported interactions to date. To address this issue, the Gene-Lifestyle Interactions Working Group within the Cohorts for Heart and Aging Research in Genetic Epidemiology Consortium has been spearheading efforts to investigate G × E in large and diverse samples through meta-analysis. Here, we present a powerful new approach to screen for interactions across the genome, an approach that shares substantial similarity to the Mendelian randomization framework. We identify and confirm 5 loci (6 independent signals) interacted with either cigarette smoking or alcohol consumption for serum lipids, and empirically demonstrate that interaction and mediation are the major contributors to genetic effect size heterogeneity across populations. The estimated lower bound of the interaction and environmentally mediated heritability is significant (P < 0.02) for low-density lipoprotein cholesterol and triglycerides in Cross-Population data. Our study improves the understanding of the genetic architecture and environmental contributions to complex traits.

12.
Disabil Health J ; : 101616, 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38514296

RESUMO

BACKGROUND: Meeting the 24-h movement guidelines (i.e., physical activity, sedentary behavior, sleep) could generate health benefits to people with disabilities. However, no systematic reviews or meta-analyses have examined the prevalence of meeting these guidelines and associations with health indicators in this group. OBJECTIVE: This systematic review and meta-analysis aimed to examine the prevalence of meeting the 24-h movement guidelines and associations with health indicators among people with disabilities. METHODS: Six electronic databases were searched for studies published in English from inception to May 31, 2023. Meta-analyses with the random-effects model were used to determine the prevalence of meeting the 24-h movement guidelines. Qualitative syntheses were employed to describe the associations between meeting the guidelines and health indicators. RESULTS: Twenty-four studies comprising 77510 participants (41.6% females) with disabilities aged 6-65 years from eight countries were identified. Overall, 6.97% of the participants with disabilities met all 24-h movement guidelines, and 16.65% met none of the guidelines. Significant age (P = 0.006) and disability type (P = 0.001) differences were found in meeting all guidelines. Participants with disabilities who met all guidelines reported better psychosocial health indicators (9/9 studies) than those met none or only one of the guidelines. There was limited evidence or research for other health indicators. CONCLUSION: There is some evidence showing that the prevalence of meeting all 24-h movement guidelines in people with disabilities is low. Meanwhile, there is preliminary evidence suggesting that meeting all guidelines is associated with better psychosocial health than meeting none of the guidelines.

13.
J Hazard Mater ; 469: 133961, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38490148

RESUMO

Aeration of sediments could induce the release of endogenous heavy metals (HMs) into overlying water. In this study, experiments involving FeS oxygenation and contaminated sediment aeration were conducted to explore the sequestering role of zeolite in the released HMs during sediment aeration. The results reveal that the dynamic processes of Fe(II) oxidation play a crucial role in regulating HMs migration during both FeS oxygenation and sediment aeration in the absence of zeolite. Based on the release of HMs, Fe(II) oxidation can be delineated into two stages: stage I, where HMs (Mn2+, Zn2+, Cd2+, Ni2+, Cu2+) are released from minerals or sediments into suspension, and stage II, released HMs are partially re-sequestered back to mineral phases or sediments due to the generation of Fe-(oxyhydr) oxide. In contrast, the addition of zeolite inhibits the increase of HMs concentration in suspension during stage I. Subsequently, the redistribution of HMs between zeolite and the newly formed Fe-(oxyhydr) oxide occurs during stage II. This redistribution of HMs generates new sorption sites in zeolite, making them available for resorbing a new load of HMs. The outcomes of this study provide potential solutions for sequestering HMs during the sediment aeration.

14.
J Colloid Interface Sci ; 664: 868-881, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38493652

RESUMO

Conversion of CO2 into high value-added fuels through the photothermal effect is an effective approach for utilizing solar energy. In this study, we prepared the CN-based photocatalyst Py-CTN-Au with both donor-acceptor (D-A) system and dual photothermal effects using a simple two-step method involving calcination and photo-deposition. Real-time monitoring with a thermal imaging camera revealed that Py-CTN-Au0.5 achieved a maximum stable temperature of 180 °C, which was approximately 1.2 times higher than that of Py-CTN (155 °C) and 1.9 times higher than that of g-CN (95 °C) under the same reaction conditions. Under the optimized reaction conditions, Py-CTN-Au0.5 exhibited a CO release rate of 30.59 umol g-1 after 4 h of reaction, which was 7.3 times higher than that of pure g-CN (4.18 umol g-1). The D-A system not only facilitated the separation and transformation of charge carriers but also induced a photothermal effect to accelerate the photoreduction of CO2. Additionally, the cocatalyst Au nanoparticles (Au NPs) further enhanced the charge carrier dynamics and photothermal effect by increasing the built-in electric field intensity and localized surface plasmon resonance (LSPR) effect, respectively. The dual photothermal effects resulting from the non-radiative photon conversion of the D-A structure and the Au NPs LSPR effect, along with the enhanced charge carrier dynamics, catalyzed the efficient photoreduction of CO2. DFT simulations were used to confirm the effect of D-A system and Au NPs. In-situ FTIR results demonstrated that the synergistic photothermal effect promoted the formation of the key intermediate species COOH*, which is beneficial for the photocatalytic reduction of CO2. This study provides valuable insights into the multiple photothermal synergistic effects in photocatalytic reactions.

15.
Nature ; 627(8004): 680-687, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38448587

RESUMO

Methods for selective covalent modification of amino acids on proteins can enable a diverse array of applications, spanning probes and modulators of protein function to proteomics1-3. Owing to their high nucleophilicity, cysteine and lysine residues are the most common points of attachment for protein bioconjugation chemistry through acid-base reactivity3,4. Here we report a redox-based strategy for bioconjugation of tryptophan, the rarest amino acid, using oxaziridine reagents that mimic oxidative cyclization reactions in indole-based alkaloid biosynthetic pathways to achieve highly efficient and specific tryptophan labelling. We establish the broad use of this method, termed tryptophan chemical ligation by cyclization (Trp-CLiC), for selectively appending payloads to tryptophan residues on peptides and proteins with reaction rates that rival traditional click reactions and enabling global profiling of hyper-reactive tryptophan sites across whole proteomes. Notably, these reagents reveal a systematic map of tryptophan residues that participate in cation-π interactions, including functional sites that can regulate protein-mediated phase-separation processes.


Assuntos
Cátions , Ciclização , Indicadores e Reagentes , Proteínas , Triptofano , Cátions/química , Indicadores e Reagentes/química , Oxirredução , Proteoma/química , Triptofano/química , Peptídeos/química , Química Click , Proteínas/química
16.
Exp Eye Res ; 242: 109862, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38490292

RESUMO

The continual exposure of retinal tissues to oxidative stress leads to discernible anatomical and physiological alterations. Specifically, the onslaught of oxidative damage escalates the irreversible death of retinal pigmented epithelium (RPE) cells, pinpointed as the fundamental pathological event in dry age-related macular degeneration (AMD). There is a conspicuous lack of effective therapeutic strategies to counteract this degenerative process. This study screened a library of antioxidants for their ability to protect RPE cells against oxidative stress and identified L-ergothioneine (EGT) as a potent cytoprotective agent. L-ergothioneine provided efficient protection against oxidative stress-damaged RPE and maintained cell redox homeostasis and normal physiological functions. It maintained the normal structure of the retina in mice under oxidative stress conditions. Transcriptomic analysis revealed that EGT counteracted major gene expression changes induced by oxidative stress. It upregulated antioxidant gene expression and inhibited NRF2 translocation. The inhibition of NRF2 abolished EGT's protective effects, suggesting that NRF2 activation contributes to its mechanism of action. In conclusion, we identified EGT as a safe and effective small-molecule compound that is expected to be a novel antioxidative agent for treating AMD.

17.
Front Bioeng Biotechnol ; 12: 1276795, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38449677

RESUMO

Dynamic assessment of cerebral blood flow (CBF) is crucial for guiding personalized management and treatment strategies, and improving the prognosis of stroke. However, a safe, reliable, and effective method for dynamic CBF evaluation is currently lacking in clinical practice. In this study, we developed a CBF monitoring system utilizing electromagnetic coupling sensing (ECS). This system detects variations in brain conductivity and dielectric constant by identifying the resonant frequency (RF) in an equivalent circuit containing both magnetic induction and electrical coupling. We evaluated the performance of the system using a self-made physical model of blood vessel pulsation to test pulsatile CBF. Additionally, we recruited 29 healthy volunteers to monitor cerebral oxygen (CO), cerebral blood flow velocity (CBFV) data and RF data before and after caffeine consumption. We analyzed RF and CBFV trends during immediate responses to abnormal intracranial blood supply, induced by changes in vascular stiffness, and compared them with CO data. Furthermore, we explored a method of dynamically assessing the overall level of CBF by leveraging image feature analysis. Experimental testing substantiates that this system provides a detection range and depth enhanced by three to four times compared to conventional electromagnetic detection techniques, thereby comprehensively covering the principal intracranial blood supply areas. And the system effectively captures CBF responses under different intravascular pressure stimulations. In healthy volunteers, as cerebral vascular stiffness increases and CO decreases due to caffeine intake, the RF pulsation amplitude diminishes progressively. Upon extraction and selection of image features, widely used machine learning algorithms exhibit commendable performance in classifying overall CBF levels. These results highlight that our proposed methodology, predicated on ECS and image feature analysis, enables the capture of immediate responses of abnormal intracranial blood supply triggered by alterations in vascular stiffness. Moreover, it provides an accurate diagnosis of the overall CBF level under varying physiological conditions.

18.
J Imaging Inform Med ; 37(1): 196-208, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38343213

RESUMO

Lung cancer is the leading cause of cancer death. Since lung cancer appears as nodules in the early stage, detecting the pulmonary nodules in an early phase could enhance the treatment efficiency and improve the survival rate of patients. The development of computer-aided analysis technology has made it possible to automatically detect lung nodules in Computed Tomography (CT) screening. In this paper, we propose a novel detection network, TiCNet. It is attempted to embed a transformer module in the 3D Convolutional Neural Network (CNN) for pulmonary nodule detection on CT images. First, we integrate the transformer and CNN in an end-to-end structure to capture both the short- and long-range dependency to provide rich information on the characteristics of nodules. Second, we design the attention block and multi-scale skip pathways for improving the detection of small nodules. Last, we develop a two-head detector to guarantee high sensitivity and specificity. Experimental results on the LUNA16 dataset and PN9 dataset showed that our proposed TiCNet achieved superior performance compared with existing lung nodule detection methods. Moreover, the effectiveness of each module has been proven. The proposed TiCNet model is an effective tool for pulmonary nodule detection. Validation revealed that this model exhibited excellent performance, suggesting its potential usefulness to support lung cancer screening.

19.
Clin Exp Pharmacol Physiol ; 51(4): e13846, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38382536

RESUMO

Hyperglycaemia is a key factor in the progression of diabetes complications. Dapagliflozin (DAPA), a new type of hypoglycaemic agent, has been shown to play an important role in anti-apoptotic, anti-inflammatory and antioxidant activities. Previous studies have demonstrated an endothelial protective effect of DAPA, but the underlying mechanism was still unclear. Autophagy is a homeostatic cellular mechanism that circulates unfolded proteins and damaged organelles through lysosomal dependent degradation. In this study, we aimed to investigate whether DAPA plays a protective role against high glucose (HG)-induced endothelial injury through regulating autophagy. The results showed that DAPA treatment resulted in increased cell viability. Additionally, DAPA treatment decreased interleukin (IL)-1ß, IL-6, and tumour necrosis factor-α levels in endothelial cells subjected to HG conditions. We observed that HG inhibited autophagy, and DAPA increased the autophagy level by inhibiting the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway. Chloroquine reversed all of these beneficial effects as an autophagy inhibitor. In summary, the endothelial protective effect of DAPA in HG can be attributed in part to its role in activating of autophagy via the AKT/mTOR signalling pathway. Therefore, suggesting that the activation of autophagy by DAPA may be a novel target for the treatment of HG-induced endothelial cell injury.


Assuntos
Autofagia , Compostos Benzidrílicos , Glucosídeos , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Endoteliais da Veia Umbilical Humana , Serina-Treonina Quinases TOR/metabolismo , Glucose/metabolismo
20.
Genes (Basel) ; 15(2)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38397155

RESUMO

Porcine epidemic diarrhea (PED) virus (PEDV) is one of the main pathogens causing diarrhea in piglets and fattening pigs. The clinical signs of PED are vomiting, acute diarrhea, dehydration, and mortality resulting in significant economic losses and becoming a major challenge in the pig industry. PEDV possesses various crucial structural and functional proteins, which play important roles in viral structure, infection, replication, assembly, and release, as well as in escaping host innate immunity. Over the past few years, there has been progress in the study of PEDV pathogenesis, revealing the crucial role of the interaction between PEDV viral proteins and host cytokines in PEDV infection. At present, the main control measure against PEDV is vaccine immunization of sows, but the protective effect for emerging virus strains is still insufficient, and there is no ideal safe and efficient vaccine. Although scientists have persistently delved their research into the intricate structure and functionalities of the PEDV genome and viral proteins for years, the pathogenic mechanism of PEDV remains incompletely elucidated. Here, we focus on reviewing the research progress of PEDV structural and nonstructural proteins to facilitate the understanding of biological processes such as PEDV infection and pathogenesis.


Assuntos
Infecções por Coronavirus , Vírus da Diarreia Epidêmica Suína , Vacinas , Animais , Suínos , Feminino , Infecções por Coronavirus/veterinária , Proteínas Virais , Diarreia/veterinária
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