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1.
Materials (Basel) ; 17(15)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39124349

RESUMO

As the integration of chips in 3D integrated circuits (ICs) increases and the size of micro-bumps reduces, issues with the reliability of service due to electromigration and thermomigration are becoming more prevalent. In the practical application of solder joints, an increase in the grain size of intermetallic compounds (IMCs) has been observed during the reflow process. This phenomenon results in an increased thickness of the IMC layer, accompanied by a proportional increase in the volume of the IMC layer within the joint. The brittle nature of IMC renders it susceptible to excessive growth in small-sized joints, which has the potential to negatively impact the reliability of the welded joint. It is therefore of the utmost importance to regulate the formation and growth of IMCs. The following paper presents the electrodeposition of a Ni-W layer on a Cu substrate, forming a barrier layer. Subsequently, the barrier properties between the Sn/Cu reactive couples were subjected to a comprehensive and systematic investigation. The study indicates that the Ni-W layer has the capacity to impede the diffusion of Sn atoms into Cu. Furthermore, the Ni-W layer is a viable diffusion barrier at the Sn/Cu interface. The "bright layer" Ni2WSn4 can be observed in all Ni-W coatings during the soldering reflow process, and its growth was almost linear. The structure of the Ni-W layer is such that it reduces the barrier properties that would otherwise be inherent to it. This is due to the "bright layer" Ni2WSn4 that covers the original Ni-W barrier layer. At a temperature of 300 °C for a duration of 600 s, the Ni-W barrier layer loses its blocking function. Once the "bright layer" Ni2WSn4 has completely covered the original Ni-W barrier layer, the diffusion activation energy for Sn diffusion into the Cu substrate side will be significantly reduced, particularly in areas where the distortion energy is concentrated due to electroplating tension. Both the "bright layer" Ni2WSn4 and Sn will grow rapidly, with the formation of Cu-Sn intermetallic compounds (IMCs). At temperatures of 250 °C, the growth of Ni3Sn4-based IMCs is controlled by grain boundaries. Conversely, the growth of the Ni2WSn4 layer (consumption of Ni-W layer) is influenced by a combination of grain boundary diffusion and bulk diffusion. At temperatures of 275 °C and 300 °C, the growth of Ni3Sn4-based IMCs and the Ni2WSn4 layer (consumption of Ni-W layer) are both controlled by grain boundaries. The findings of this study can inform the theoretical design of solder joints with barrier layers as well as the selection of Ni-W diffusion barrier layers for use in different soldering processes. This can, in turn, enhance the reliability of microelectronic devices, offering significant theoretical and practical value.

2.
Gastroenterology ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39147169

RESUMO

BACKGROUND AND AIMS: Peritoneal metastasis (PM) in gastric cancer (GC) is associated with poor prognosis and significant morbidity. We sought to understand the genomic, transcriptomic, and tumor microenvironment (TME) features that contribute to peritoneal organotropism in GC. METHODS: We conducted a comprehensive multi-omic analysis of 548 samples from 326 patients, including primary tumors, matched normal tissues, peritoneal metastases, and adjacent-normal peritoneal tissues. We employed whole exome sequencing, whole transcriptome sequencing, and digital spatial profiling to investigate molecular alterations, gene expression patterns, and TME characteristics associated with PM. RESULTS: Our analysis identified specific genomic alterations in primary tumors, including mutations in ELF3, CDH1, and PIGR, and TME signatures, such as stromal infiltration and M2 macrophage enrichment, associated with increased risk of PM. We observed distinct transcriptional programs and immune compositions in GCPM compared to liver metastases, highlighting the importance of the TME in transcoelomic metastasis. We found differential expression of therapeutic targets between primary tumors and PM, with lower CLDN18.2 and FGFR2b expression in PM. We unravel the roles of the TME in niche reprogramming within the peritoneum, and provide evidence of pre-metastatic niche conditioning even in early GC without clinical PM. These findings were further validated using a humanized mouse model, which demonstrated niche remodeling in the peritoneum during transcoelomic metastasis. CONCLUSION: Our study provides a comprehensive molecular characterization of GCPM and unveils key biological principles underlying transcoelomic metastasis. The identified predictive markers, therapeutic targets, and TME alterations offer potential avenues for targeted interventions and improved patient outcomes.

3.
Animals (Basel) ; 14(13)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38998073

RESUMO

Equine breeding plays an essential role in the local economic development of many countries, and it has experienced rapid growth in China in recent years. However, the equine industry, particularly large-scale donkey farms, faces a significant challenge with pregnancy losses. Unfortunately, there is a lack of systematic research on abortion during equine breeding. Several causes, both infectious and non-infectious, of pregnancy losses have been documented in equines. The infectious causes are viruses, bacteria, parasites, and fungi. Non-infectious causes may include long transportation, ingestion of mycotoxins, hormonal disturbances, twinning, placentitis, umbilical length and torsion, etc. In current review, we discuss the transmission routes, diagnostic methods, and control measures for these infectious agents. Early detection of the cause and appropriate management are crucial in preventing pregnancy loss in equine practice. This review aims to provide a comprehensive understanding of the potential causes of abortion in equines, including infectious agents and non-infectious factors. It emphasizes the importance of continued research and effective control measures to address this significant challenge in the equine industry.

4.
ACS Omega ; 9(26): 28028-28036, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38973857

RESUMO

Although the annual branches of apple trees are substantial, most of them are discarded or incinerated, resulting in a significant waste of resources and environmental pollution concerns. Therefore, it has become necessary and urgent to recycle these branches. Compared with crop straw, apple tree pruning branches exhibit a relatively elevated lignin content, which makes them an optimal feedstock for generating high-quality pyrolysis gases. Energy yield can comprehensively measure the gas production and heat value of the pyrolysis gas. Herein, the effect of reaction conditions on the energy yield of the pyrolysis gas is systematically investigated. The single-factor experimental results show that the optimal conditions are 750 °C reaction temperature, 2 °C/min heating rate, and 120 min holding time. The central composite design test of the response surface establishes that temperature has the most impact, followed by heating rate and holding time. In addition, a regression model is constructed to predict the energy yield of the pyrolysis gas. The analysis of interactions between factors indicates that factors within the lower temperature zones, higher heating rate, and shorter holding time have a more significant influence on the energy yield. These findings provide crucial guidance for the efficient production of pyrolysis gas from apple tree branches.

5.
J Oral Rehabil ; 51(9): 1684-1691, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38924570

RESUMO

OBJECTIVES: Noncarious cervical lesions (NCCLs) are multifactorial and can be caused by the anatomical structure of the teeth, erosion, abrasion and abnormal occlusion. The aim of this case-control study was to explore the risk factors for NCCLs. METHODS: Cone-beam computed tomography was used to determine whether a wedge-shaped defect existed at the cementoenamel junction. We compared 63 participants with NCCLs with 63 controls without NCCLs, matched for sex, age (±1 year) and toothbrushing-related factors (e.g., type of bristle and brushing patterns, frequency and strength). All participants were asked to complete a questionnaire about self-administered daily diet habits and health condition. Univariate and multivariate logistic regression analyses were conducted to determine the risk factors for NCCLs. RESULTS: Significant variables in the univariate analysis (i.e., p < .2) included frequency of carbonated beverage consumption, sella-nasion-point B angle (SNB) and Frankfort-mandibular plane angle (FMA). Multivariate logistic regression demonstrated that the consumption frequency of carbonated beverages (odds ratio [OR] = 3.147; 95% confidence interval [CI], 1.039-9.532), FMA (OR = 1.100; 95% CI, 1.004-1.204) and SNB (OR = 0.896; 95% CI, 0.813-0.988) was independent influencing factors. The area under the receiver operating characteristic curve (AUC) value of regression Model 1 (established with the frequency of carbonated beverage consumption, FMA, SNB and sleep bruxism) was 0.700 (95% CI, 0.607-0.792; p < .001), and that of regression Model 2 (established using the frequency of carbonated beverage consumption, FMA and SNB) was 0.704 (95% CI, 0.612-0.796; p < .001). CONCLUSIONS: The consumption frequency of carbonated beverages and FMA was risk factors for NCCLs; the higher the frequency of carbonated beverage consumption and FMA, the higher was the probability of NCCLs. SNB was a protective factor for NCCL occurrence; the larger the SNB, the lower was the probability of NCCL occurrence. These findings have further clarified the aetiology of NCCLs and provided clinicians with valuable insights into strategies for preventing the loss of dental tissue.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Colo do Dente , Escovação Dentária , Humanos , Feminino , Estudos de Casos e Controles , Fatores de Risco , Masculino , Adulto , Colo do Dente/patologia , Colo do Dente/diagnóstico por imagem , Escovação Dentária/estatística & dados numéricos , Pessoa de Meia-Idade , Bebidas Gaseificadas/efeitos adversos , Erosão Dentária/etiologia , Erosão Dentária/epidemiologia , Comportamento Alimentar , Inquéritos e Questionários
6.
Sci Rep ; 14(1): 10295, 2024 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704415

RESUMO

Lysine crotonylation (Kcr) is a recently discovered histone acylation modification that is closely associated with gene expression, cell proliferation, and the maintenance of stem cell pluripotency and indicates the transcriptional activity of genes and the regulation of various biological processes. During cell culture, the introduction of exogenous croconic acid disodium salt (Nacr) has been shown to modulate intracellular Kcr levels. Although research on Kcr has increased, its role in cell growth and proliferation and its potential regulatory mechanisms remain unclear compared to those of histone methylation and acetylation. Our investigation demonstrated that the addition of 5 mM Nacr to cultured bovine fibroblasts increased the expression of genes associated with Kcr modification, ultimately promoting cell growth and stimulating cell proliferation. Somatic cell nuclear transfer of donor cells cultured in 5 mM Nacr resulted in 38.1% blastocyst development, which was significantly greater than that in the control group (25.2%). This research is important for elucidating the crotonylation modification mechanism in fibroblast proliferation to promote the efficacy of somatic cell nuclear transfer.


Assuntos
Proliferação de Células , Fibroblastos , Histonas , Técnicas de Transferência Nuclear , Animais , Bovinos , Fibroblastos/metabolismo , Fibroblastos/citologia , Proliferação de Células/efeitos dos fármacos , Histonas/metabolismo , Desenvolvimento Embrionário , Blastocisto/metabolismo , Blastocisto/citologia , Lisina/metabolismo , Crotonatos/metabolismo , Células Cultivadas , Processamento de Proteína Pós-Traducional , Feminino
7.
Opt Lett ; 49(5): 1341-1344, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38427008

RESUMO

We propose and demonstrate a tunable fractional-order photonic differentiator (DIFF) that can process input pulses with a sub-gigahertz bandwidth. Our scheme utilizes the self-induced optical modulation effect observed in a silicon-on-insulator micro-ring resonator. Gaussian-like pulses with varying pulse widths between 7.5 and 20 ns are employed for differentiation, achieving an energy efficiency over 45%, to the best of our knowledge, which surpasses all previously reported schemes for input pulses with a sub-gigahertz bandwidth. We simulate the temporal dynamics of pulses to gain insight into the physical mechanisms underlying the differentiated outputs and provide a method for differentiation order adjustment, which is experimentally realized using an all-optical pump-probe technique.

8.
Bioresour Technol ; 399: 130611, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38508282

RESUMO

Glucosylglycerate (R-2-O-α-D-glucopyranosyl-glycerate, GG) is a negatively charged compatible solution with versatile functions. Here, an artificial in vitro enzymatic cascade was designed to feasibly and sustainably produce GG from affordable starch and glycerol. First, Spirochaeta thermophila glucosylglycerate phosphorylase (GGP) was carefully selected because of its excellent heterologous expression, specific activity, and thermostability. The optimized two-enzyme cascade, consisting of alpha-glucan phosphorylase (αGP) and GGP, achieved a remarkable 81 % conversion rate from maltodextrin and D-glycerate. Scaling up this cascade resulted in a practical concentration of 58 g/L GG with a 62 % conversion rate based on the added D-glycerate. Additionally, the production of GG from inexpensive starch and glycerol in one-pot using artificial four-enzyme cascade was successfully implemented, which integrates alditol oxidase and catalase with αGP and GGP. Collectively, this sustainable enzymatic cascade demonstrates the feasibility of the practical synthesis of GG and has the potential to produce other glycosides using the phosphorylase-and-phosphorylase paradigm.


Assuntos
Glicerol , Amido , Glucosídeos/metabolismo , Fosforilases/metabolismo
9.
Genes (Basel) ; 15(2)2024 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-38397242

RESUMO

Numerous studies have shown that combining populations from similar or closely related genetic breeds improves the accuracy of genomic predictions (GP). Extensive experimentation with diverse Bayesian and genomic best linear unbiased prediction (GBLUP) models have been developed to explore multi-breed genomic selection (GS) in livestock, ultimately establishing them as successful approaches for predicting genomic estimated breeding value (GEBV). This study aimed to assess the effectiveness of using BayesR and GBLUP models with linkage disequilibrium (LD)-weighted genomic relationship matrices (GRMs) for genomic prediction in three different beef cattle breeds to identify the best approach for enhancing the accuracy of multi-breed genomic selection in beef cattle. Additionally, a comparison was conducted to evaluate the predictive precision of different marker densities and genetic correlations among the three breeds of beef cattle. The GRM between Yunling cattle (YL) and other breeds demonstrated modest affinity and highlighted a notable genetic concordance of 0.87 between Chinese Wagyu (WG) and Huaxi (HX) cattle. In the within-breed GS, BayesR demonstrated an advantage over GBLUP. The prediction accuracies for HX cattle using the BayesR model were 0.52 with BovineHD BeadChip data (HD) and 0.46 with whole-genome sequencing data (WGS). In comparison to the GBLUP model, the accuracy increased by 26.8% for HD data and 9.5% for WGS data. For WG and YL, BayesR doubled the within-breed prediction accuracy to 14.3% from 7.1%, outperforming GBLUP across both HD and WGS datasets. Moreover, analyzing multiple breeds using genomic selection showed that BayesR consistently outperformed GBLUP in terms of predictive accuracy, especially when using WGS. For instance, in a mixed reference population of HX and WG, BayesR achieved a significant accuracy of 0.53 using WGS for HX, which was a substantial enhancement over the accuracies obtained with GBLUP models. The research further highlights the benefit of including various breeds in the reference group, leading to enhanced accuracy in predictions and emphasizing the importance of comprehensive genomic selection methods. Our research findings indicate that BayesR exhibits superior performance compared to GBLUP in multi-breed genomic prediction accuracy, achieving a maximum improvement of 33.3%, especially in genetically diverse breeds. The improvement can be attributed to the effective utilization of higher single nucleotide polymorphism (SNP) marker density by BayesR, resulting in enhanced prediction accuracy. This evidence conclusively demonstrates the significant impact of BayesR on enhancing genomic predictions in diverse cattle populations, underscoring the crucial role of genetic relatedness in selection methodologies. In parallel, subsequent studies should focus on refining GRM and exploring alternative models for GP.


Assuntos
Genoma , Genômica , Bovinos/genética , Animais , Teorema de Bayes , Genoma/genética , Genômica/métodos , Desequilíbrio de Ligação , Polimorfismo de Nucleotídeo Único/genética
10.
CNS Neurosci Ther ; 30(2): e14613, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38379185

RESUMO

AIMS: Alzheimer's disease (AD) is a significant global health concern, and it is crucial that we find effective methods to prevent or slow down AD progression. Recent studies have highlighted the essential role of blood vessels in clearing Aß, a protein that contributes to AD. Scientists are exploring blood biomarkers as a potential tool for future AD diagnosis. One promising method that may help prevent AD is remote ischemic conditioning (RIC). RIC involves using sub-lethal ischemic-reperfusion cycles on limbs. However, a comprehensive understanding of how RIC can prevent AD and its long-term effectiveness is still lacking. Further research is essential to fully comprehend the potential benefits of RIC in preventing AD. METHODS: Female wild-type (WT) and APP/PS1 transgenic rats, aged 12 months, underwent ovariectomy and were subsequently assigned to WT, APP/PS1, and APP/PS1 + RIC groups. RIC was conducted five times a week for 4 weeks. The rats' depressive and cognitive behaviors were evaluated using force swimming, open-field tests, novel objective recognition, elevated plus maze, and Barnes maze tests. Evaluation of the neurovascular unit (NVU), synapses, vasculature, astrocytes, and microglia was conducted using immunofluorescence staining (IF), Western blot (WB), and transmission electron microscopy (TEM). Additionally, the cerebro-vasculature was examined using micro-CT, and cerebral blood flow (CBF) was measured using Speckle Doppler. Blood-brain barrier (BBB) permeability was determined by measuring the Evans blue leakage. Finally, Aß levels in the rat frontal cortex were measured using WB, ELISA, or IF staining. RESULTS: RIC enhanced memory-related protein expression and rescued depressive-like behavior and cognitive decline in APP/PS1 transgenic rats. Additionally, the intervention protected NVU in the rat frontal cortex, as evidenced by (1) increased expression of TJ (tight junction) proteins, pericyte marker PDGFRß, and glucose transporter 1 (GLUT1), as well as decreased VCAM1; (2) mitigation of ultrastructure impairment in neuron, cerebral vascular, and astrocyte; (3) upregulation of A2 astrocyte phenotype markers and downregulation of A1 phenotype markers, indicating a shift toward a healthier phenotype. Correspondingly, RIC intervention alleviated neuroinflammation, as evidenced by the decreased Iba1 level, a microglia marker. Meanwhile, RIC intervention elevated CBF in frontal cortex of the rats. Notably, RIC intervention effectively suppressed Aß toxicity, as demonstrated by the enhancement of α-secretase and attenuation of ß-secretase (BACE1) and γ- secretase and Aß1-42 and Aß1-40 levels as well. CONCLUSION: Chronic RIC intervention exerts vascular and neuroprotective roles, suggesting that RIC could be a promising therapeutic strategy targeting the BBB and NVU during AD development.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Camundongos , Ratos , Feminino , Animais , Barreira Hematoencefálica/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Camundongos Transgênicos , Ratos Transgênicos , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Ácido Aspártico Endopeptidases/uso terapêutico , Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/terapia , Modelos Animais de Doenças , Presenilina-1/genética , Presenilina-1/metabolismo
11.
PLoS One ; 19(2): e0297868, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38358991

RESUMO

Entrepreneurial ventures are established in large numbers in China. The success rate of these entrepreneurial ventures is lower than that of new startups. Mismanagement and a lack of creative skills among entrepreneurs are cited as reasons for entrepreneurial failure in China. The current study investigates the impact of entrepreneurial networking and new venture intention on entrepreneurial success in China, with psychological capital and entrepreneurial optimism serving as moderators. 483 responses were collected from business students in China for data analysis. The findings of the study reveal that the impact of entrepreneurial networking and new venture intention on entrepreneurial success in China, with the moderating role of psychological capital and entrepreneurial optimism, is significant. The theoretical framework of this research has novelty as it introduces new moderating relationships of psychological capital and entrepreneurial optimism in the model of entrepreneurial success. Practically, this study has revealed that entrepreneurial success can be achieved with entrepreneurial networking, entrepreneurial optimism, psychological capital, and new venture intention. The directions of this research point out additional gaps in the literature that scholars should discuss in subsequent studies.


Assuntos
Comércio , Empreendedorismo , Humanos , China , Análise de Dados , Estudantes
12.
Medicine (Baltimore) ; 103(1): e36840, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-38181256

RESUMO

To investigate the influencing factors of in-hospital acute heart failure (AHF) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to construct and validate a risk prediction nomogram model. Three Hundred Thirty patients with AECOPD admitted to our hospital from June 2020 to June 2023 were retrospectively analyzed as a training set for the construction of the model. Three Hundred Twenty-five AECOPD patients admitted to the Second People's Hospital of Hefei from 2006 to June 2023 were also collected as the validation set for the validation of the model. A nomogram model was constructed to predict the risk of nosocomial AHF in patients with AECOPD, and C-index and receiver operating characteristic curve were drawn to assess the predictive predictive efficacy of the model. Model fit was evaluated by Hosmer-Lemeshow test, calibration curve was drawn to evaluate the calibration of the model; decision curve was drawn to analyze the net benefit rate of this nomogram model. Multivariate logistic regression analysis indicated that body mass index, mmRC grade, neutrophils, lymphocytes, hemoglobin, creatinine, PO2, PCO2, and Homocysteine were independent risk factors for in-hospital AHF in patients with AECOPD. To construct a nomogram model for risk prediction of in-hospital AHF in patients with AECOPD. The C-index of the training set was 0.949 (95% CI: 0.91-0.961); the C-index of the validation set was 0.936 (95% CI: 0.911-0.961) suggesting good model discrimination. The receiver operating characteristic curve calculated area under curve for the training set was 0.949 (95% CI: 0.928-0.97); area under curve for the validation set was 0.936 (95% CI: 0.91-0.961) suggesting good model accuracy. The results of Hosmer-Lemeshoe goodness-of-fit test and calibration curve analysis showed that the calibration curve of this nomogram model was close to the ideal curve. The clinical decision curve also showed good clinical net benefit of the nomogram model. Body mass index, mmRC grade, neutrophils, lymphocytes, hemoglobin, creatinine, PO2, PCO2, and Homocysteine are risk factors for in-hospital AHF in AECOPD patients, and nomogram models constructed based on the above factors have some predictive value for in-hospital AHF in AECOPD patients. It is also vital for nursing staff to strengthen nursing care.


Assuntos
Insuficiência Cardíaca , Doença Pulmonar Obstrutiva Crônica , Humanos , Creatinina , Nomogramas , Estudos Retrospectivos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Homocisteína , Doença Pulmonar Obstrutiva Crônica/complicações , Hemoglobinas
13.
J Colloid Interface Sci ; 659: 320-329, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38176241

RESUMO

The efficacy of imaging-guided photodynamic therapy (PDT) is compromised by the attenuation of fluorescence and decline in reactive oxygen species (ROS) generation efficiency in the physiological environment of conventional photosensitizers, limited near-infrared (NIR) absorption, and high systemic cytotoxicity. This paper presents the synthesis of two cyclometalated Ir (III) complexes (Ir-thpy and Ir-ppy) by using a triphenylamine derivative (DPTPA) as the primary ligand and their encapsulation into an amphiphilic phospholipid to form nanoparticles (NPs). These complexes exhibit aggregation-induced emission features and remarkably enhanced ROS generation compared to Chlorin e6 (Ce6). Moreover, Ir-thpy NPs possess the unique ability to selectively target mitochondria, leading to depolarization of the mitochondrial membrane potential and ultimately triggering apoptosis. Notably, Ir-thpy NPs exhibit exceptional photocytotoxicity even towards cisplatin-resistant A549/DDP tumor cells. In vivo two-photon imaging verified the robust tumor-targeting efficacy of Ir-thpy NPs. The in vivo results unequivocally demonstrate that Ir-thpy NPs exhibit excellent tumor ablation along with remarkable biocompatibility. This study presents a promising approach for the development of multifunctional Ir-NPs for two-photon imaging-guided PDT and provides novel insights for potential clinical applications in oncology.


Assuntos
Nanopartículas , Fotoquimioterapia , Irídio/farmacologia , Espécies Reativas de Oxigênio , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Mitocôndrias , Linhagem Celular Tumoral
14.
Hepatology ; 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38051951

RESUMO

BACKGROUND AND AIMS: Cross talk between tumor cells and immune cells enables tumor cells to escape immune surveillance and dictate responses to immunotherapy. Previous studies have identified that downregulation of the glycolytic enzyme fructose-1,6-bisphosphate aldolase B (ALDOB) in tumor cells orchestrated metabolic programming to favor HCC. However, it remains elusive whether and how ALDOB expression in tumor cells affects the tumor microenvironment in HCC. APPROACH AND RESULTS: We found that ALDOB downregulation was negatively correlated with CD8 + T cell infiltration in human HCC tumor tissues but in a state of exhaustion. Similar observations were made in mice with liver-specific ALDOB knockout or in subcutaneous tumor models with ALDOB knockdown. Moreover, ALDOB deficiency in tumor cells upregulates TGF-ß expression, thereby increasing the number of Treg cells and impairing the activity of CD8 + T cells. Consistently, a combination of low ALDOB and high TGF-ß expression exhibited the worst overall survival for patients with HCC. More importantly, the simultaneous blocking of TGF-ß and programmed cell death (PD) 1 with antibodies additively inhibited tumorigenesis induced by ALDOB deficiency in mice. Further mechanistic experiments demonstrated that ALDOB enters the nucleus and interacts with lysine acetyltransferase 2A, leading to inhibition of H3K9 acetylation and thereby suppressing TGFB1 transcription. Consistently, inhibition of lysine acetyltransferase 2A activity by small molecule inhibitors suppressed TGF-ß and HCC. CONCLUSIONS: Our study has revealed a novel mechanism by which a metabolic enzyme in tumor cells epigenetically modulates TGF-ß signaling, thereby enabling cancer cells to evade immune surveillance and affect their response to immunotherapy.

15.
Opt Express ; 31(25): 42191-42205, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38087598

RESUMO

Large-area copper layer removal is one of the essential processes in manufacturing printed circuit boards (PCB) and frequency selective surfaces (FSS). However, laser direct ablation (LDA) with one-step scanning is challenging in resolving excessive substrate damage and material residue. Here, this study proposes a laser scanning strategy based on the laser-induced active mechanical peeling (LIAMP) effect generated by resin decomposition. This scanning strategy allows the removal of large-area copper layers from FR-4 copper-clad laminates (FR-4 CCL) in one-step scanning without additional manual intervention. During the removal process, the resin decomposition in the laser-irradiated area provides the mechanical tearing force, while the resin decomposition in the laser-unirradiated area reduces the interfacial adhesion force and provides recoil pressure. By optimizing scanning parameters to control the laser energy deposition, the substrate damage and copper residue can be effectively avoided. In our work, the maximum removal efficiency with different energy densities, pulse duration, and repetition frequency are 31.8 mm2/ms, 30.25 mm2/ms, and 82.8 mm2/ms, respectively. Compared with the reported copper removal using laser direct write lithography technology combined with wet chemical etching (LDWL+WCE) and LDA, the efficiency improved by 8.3 times and 66 times. Predictably, the laser scanning strategy and the peeling mechanism are simple and controllable, which have potential in electronics, communications, and aerospace.

16.
Opt Lett ; 48(24): 6496-6499, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38099782

RESUMO

Reflective dynamic focusing devices (RDFDs) have shown their potential in laser scanning as high-performance laser Z-direction focusing devices. However, the scanning range of RDFD-based scanners is limited by aberrations during dynamic focusing. An aspheric symmetry correction (ASC) method was proposed to extend the effective scanning range. An aspheric lens was introduced to correct the optical path difference (OPD) and optimize aberrations. As a result, the scanning range in the three-dimensional (3D) space increased by 15.2%. The ASC method has been proven to extend the 3D scanning range of RDFD-based scanners and may have broad application prospects.

17.
Sci Rep ; 13(1): 19108, 2023 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-37925532

RESUMO

Surface roughness affects the near-wall fluid velocity profile and surface drag, and is commonly quantified by the equivalent sand-grain roughness [Formula: see text]. It is essential to estimate [Formula: see text] for accurate fluid dynamic problem modeling. While numerous roughness correlation formulas have been proposed to predict [Formula: see text] in the fully rough regime, most of them are restricted to certain roughness types, with various geometric parameters considered in each case, leading to ongoing disagreements regarding its parameterization and lack of universality. In this study, a Particle Swarm Optimized Backpropagation (PSO-BP) method is proposed to predict [Formula: see text] based on the selected surface parameters from previous DNS, LES, and experimental results for flow behavior over various surface roughness. The PSO-BP model's ability to predict [Formula: see text] in the fully rough region is evaluated and compared with both the existing roughness correction formulas as well as the traditional BP model. An optimized polynomial function is also proposed to serve as a 'white box' for predicting [Formula: see text]. It turns out that the PSO-BP method has better performance in the evaluation metrics compared to other methods, yielding a Mean Absolute Error (MAE) of 0.0390, a Mean Squared Error (MSE) of 0.0026 and a Mean Absolute Percentage Error (MAPE) of 28.12%. This novel approach for estimating [Formula: see text] has practical applicability and holds promise for improving the precision and efficiency of calculations related to equivalent sand-grain roughness, and thus provides more accurate and effective solutions for CFD and other engineering applications.

18.
Nat Prod Res ; : 1-7, 2023 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-37943069

RESUMO

A new morphinan alkaloid (6S, 9S, 13 R, 14S)-6-O-acetyl-7,8-Didehydro-4-hydroxy-3,7-dimethoxymorphinan-6-ol (1), and a new naturally occurring cularine alkaloid (S)-2, 3, 12, 12a-tetrahydro-5, 6, 9, 10-tetramethoxy-1-methyl-1H-[1]benzoxepino[2, 3, 4-ij]isoquinoline(5), along with four known alkaloids were isolated from the roots of Stephania cepharantha. The structures of these compounds were elucidated based on spectroscopic data analyses. Cytotoxic activities of the compounds against three human cancer cell lines (A549, MCF-7 and SW480) were also evaluated.

19.
Front Netw Physiol ; 3: 1257710, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38020240

RESUMO

This study developed and investigated a comprehensive multiscale computational model of a mechanically ventilated ARDS lung to elucidate the underlying mechanisms contributing to the development or prevention of VILI. This model is built upon a healthy lung model that incorporates realistic airway and alveolar geometry, tissue distensibility, and surfactant dynamics. Key features of the ARDS model include recruitment and derecruitment (RD) dynamics, alveolar tissue viscoelasticity, and surfactant deficiency. This model successfully reproduces realistic pressure-volume (PV) behavior, dynamic surface tension, and time-dependent descriptions of RD events as a function of the ventilation scenario. Simulations of Time-Controlled Adaptive Ventilation (TCAV) modes, with short and long durations of exhalation (T Low - and T Low +, respectively), reveal a higher incidence of RD for T Low + despite reduced surface tensions due to interfacial compression. This finding aligns with experimental evidence emphasizing the critical role of timing in protective ventilation strategies. Quantitative analysis of energy dissipation indicates that while alveolar recruitment contributes only a small fraction of total energy dissipation, its spatial concentration and brief duration may significantly contribute to VILI progression due to its focal nature and higher intensity. Leveraging the computational framework, the model may be extended to facilitate the development of personalized protective ventilation strategies to enhance patient outcomes. As such, this computational modeling approach offers valuable insights into the complex dynamics of VILI that may guide the optimization of ventilation strategies in ARDS management.

20.
Animals (Basel) ; 13(20)2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37893940

RESUMO

(1) Background: Myostatin (MSTN) is a protein that regulates skeletal muscle development and plays a crucial role in maintaining animal body composition and muscle structure. The loss-of-function mutation of MSTN gene can induce the muscle hypertrophic phenotype. (2) Methods: Growth indexes and blood parameters of the cattle of different months were analyzed via multiple linear regression. (3) Results: Compared with the control group, the body shape parameters of F2 cattle were improved, especially the body weight, cross height, and hip height, representing significant development of hindquarters, and the coat color of the F2 generation returned to the yellow of Luxi cattle. As adults, MSTN gene-edited bulls have a tall, wide acromion and a deep, wide chest. Both the forequarters and hindquarters are double-muscled with clear muscle masses. The multiple linear regression demonstrates that MSTN gene-edited hybrid beef cattle gained weight due to the higher height of the hindquarters. Significant differences in blood glucose, calcium, and low-density lipoprotein. Serum insulin levels decreased significantly at 24 months of age. MSTN gene editing improves the adaptability of cattle. (4) Conclusions: Our findings suggest that breeding with MSTN gene-edited Luxi bulls can improve the growth and performance of hybrid cattle, with potential benefits for both farmers and consumers.

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