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1.
Sci Rep ; 14(1): 22472, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39341820

RESUMO

The existing deep estimation networks often overlook the issue of computational efficiency while pursuing high accuracy. This paper proposes a lightweight self-supervised network that combines convolutional neural networks (CNN) and Transformers as the feature extraction and encoding layers for images, enabling the network to capture both local geometric and global semantic features for depth estimation. First, depth-separable convolution is used to construct a dilated convolution residual module based on a shallow network to improve the shallow CNN feature extraction receptive field. In the transformer, a multidepth separable convolution head transposed attention module is proposed to reduce the computational burden of spatial self-attention. In the feedforward network, a two-step gating mechanism is proposed to improve the nonlinear representation ability of the feedforward network. Finally, the CNN and transformer are integrated to implement a depth estimation network with a local-global context interaction function. Compared with other lightweight models, this model has fewer model parameters and higher estimation accuracy. It also has better generalizability for different outdoor datasets. Additionally, the inference speed can reach 87 FPS, achieving better real-time performance and accounting for both inference speed and estimation accuracy.

2.
J Hazard Mater ; 479: 135573, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39236537

RESUMO

Fusarium graminearum, the primary pathogen responsible for wheat Fusarium head blight, can induce pulmonary damage through its spores. However, the detailed mechanism by which these spores cause intestinal injury is not yet fully understood. This study aimed to investigate the impact of exposure to fungal spores on the intestinal microbiota using a mice model that mimics the effects of fusarium graminearum spores on the gut microbiota and its metabolic profile. The study utilized 16S rRNA sequencing and metabolomics methodologies to analyze the contents of the cecum and feces in mice. The results showed that exposure to fungal spores led to significant changes in the composition of the intestinal microbiota in mice, characterized by an increase in Akkermansia and Staphylococcus populations. A non-targeted metabolomics analysis identified 316 metabolites associated with various metabolic pathways, particularly galactose metabolism. Pre-exposure to antibiotics before fungal spore exposure resulted in a decrease in the metabolic capacity of the intestinal microbiota in mice. This research demonstrates that fusarium graminearum spores can disrupt the intestinal microbiota and metabolome via the lung-gut axis. These findings provide valuable insights into the intestinal damage caused by fungal spores and offer important support for the development of therapeutic strategies for intestinal diseases.


Assuntos
Fusarium , Microbioma Gastrointestinal , Pulmão , Metaboloma , Esporos Fúngicos , Animais , Fusarium/metabolismo , Esporos Fúngicos/metabolismo , Pulmão/microbiologia , Pulmão/metabolismo , Camundongos , RNA Ribossômico 16S/genética , Masculino , Fezes/microbiologia , Metabolômica , Antibacterianos/farmacologia
3.
Environ Int ; 192: 109027, 2024 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-39332283

RESUMO

With the development of the pharmaceutical industry, halogenated hydrocarbons, which are the main raw materials and emissions of the pharmaceutical industry, may be defined as atmospheric emerging contaminants due to toxicity and low oxidation of the atmosphere. This study analyzed the volatile organic compounds (VOCs) emissions from four pharmaceutical companies located in the Yangtze River Delta. Samples were taken three times at each of the selected fixed and fugitive sampling sites in each company. Through testing, 141 VOCs were identified. The mean concentration and proportion of halogenated hydrocarbons from the four pharmaceutical companies were the highest of all the industries in the industrial park. They reached 18.9 ppm and 28.8 %, respectively. Fixed emissions of the companies exhibited the mean maximum concentration of dichloromethane and chlorobenzene, which are 11.4 ppm and 250.67 ppb. The mean concentration of fugitive emission of dichloromethane from the four companies in this study is lower than that of pharmaceutical companies in other studies. Newly detected halogenated hydrocarbons, such as 1,1-dichloropropanone and dichloronitromethane, present potential non-cancer and cancer risks to workers. Chlorobenzene was identified as a key potential cancer risk halogenated hydrocarbon the value of which reaches 0.00965. 2,6-dichloropyridine could be a potential emerging contaminant due to its lower MIR value and higher potential cancer risk. The study suggests that relevant pharmaceutical companies focus on the emissions of chlorobenzene and dichloromethane, which may be the atmospheric emerging contaminants for the pharmaceutical industry and focus on improve the treatment of waste gases in workshops and sewage stations.

4.
Sex Med ; 12(4): qfae047, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39220342

RESUMO

Background: Premature ejaculation (PE) is linked with abnormal brain activity that is modifiable by electroacupuncture (EA). Aim: In this study we aimed to explore the central pathological mechanism underlying EA in treating PE. Methods: Six-week-old male Sprague-Dawley rats were divided into a PE group (n = 8) and a control group (n = 8) according to ejaculatory frequency during copulatory behavior. All rats underwent EA at the Zusanli acupoint (ST-36) for 4 weeks. Magnetic resonance imaging data were collected before and after EA. Outcomes: The behavioral parameters, plasma norepinephrine levels, fractional amplitude of low frequency fluctuation (fALFF), and regional homogeneity (ReHo) were evaluated. Results: The PE group ejaculated more times with shorter latency compared with controls. After EA, the ejaculation frequency of the PE group decreased, and the ejaculation latency period increased, with no changes observed in the control group. Norepinephrine levels were higher in the PE group than in the controls and were positively correlated with ejaculation frequency and negatively correlated with ejaculation latency. The PE group showed lower fALFF in the right striatum and higher ReHo in the brainstem compared with controls. After EA, controls showed decreased fALFF in the right striatum, left olfactory bulb, and dorsal fornix and increased ReHo in the right interpeduncular nucleus, as well as decreased ReHo in the left striatum, prelimbic system, right basal forebrain region, septal region, and olfactory bulb, while the model group exhibited increased fALFF in the right hypothalamic region, decreased fALFF in the left globus pallidum and right basal forebrain region and increased ReHo in the right interpeduncular nucleus, as well as decreased ReHo in the left striatum, olfactory bulb, basal forebrain region, dentate gyrus, right dysgranular insular cortex, and striatum. Compared with the controls after EA, the model group showed increased ReHo of the right hypothalamic region and decreased ReHo of the right dysgranular insular cortex. Clinical Implications: These findings might enhance the understanding of PE and contribute to new, targeted therapies for PE. Strengths and Limitations: The therapeutic effects might be achieved by EA inhibiting the activity in brain regions involved in ejaculatory behavior. However, the curative effect of acupuncture might be underestimated due to some curative effects of sham acupuncture used in the control group. Conclusion: In conclusion, the ejaculatory frequency of rats may be reduced and ejaculation latency could be extended by EA at ST-36, which might be achieved by the effects of this treatment on brain activity.

5.
Nat Chem Biol ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39232187

RESUMO

Protein phosphorylation is a pivotal post-translational modification modulating various cellular processes. In Gram-positive bacteria, the protein arginine kinase McsB, along with its activator McsA, has a key role in labeling misfolded and damaged proteins during stress. However, the activation mechanism of McsB by McsA remains elusive. Here we report the cryo-electron microscopy structure of a tetrameric McsA-McsB complex at 3.41 Å resolution. Biochemical analysis indicates that the homotetrameric assembly is essential for McsB's kinase activity. The conserved C-terminal zinc finger of McsA interacts with an extended loop in McsB, optimally orienting a critical catalytic cysteine residue. In addition, McsA binding decreases the CtsR's affinity for McsB, enhancing McsB's kinase activity and accelerating the turnover rate of CtsR phosphorylation. Furthermore, McsA binding also increases McsB's thermostability, ensuring its activity under heat stress. These findings elucidate the structural basis and activation mechanism of McsB in stress response.

6.
Physiol Plant ; 176(5): e14523, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39262285

RESUMO

Garlic bulbs generally possess several swelling cloves, and the swelling degree of the bulbs determines its yield and appearance quality. However, the genetic basis underlying bulb traits remains poorly known. To address this issue, we performed a genome-wide association analysis for three bulb traits: bulb weight, diameter, and height. It resulted in the identification of 51 significant associated signals from 38 genomic regions. Twelve genes from the associated regions, whose transcript abundances in the developmental bulb showed significant correlations with the investigated traits in 81 garlic accessions, were considered the candidates of the corresponding locus. We focused on five of these candidates and their variations and revealed that the promoter variations of fructose-bisphosphate aldolase-encoding Asa8G05696.1 and beta-fructofuranosidase-encoding Asa6G01167.1 are responsible for the functional diversity of these two genes in garlic population. Interestingly, our results revealed that all candidates we focused on experienced a degree of selection during garlic evolutionary history, and different genotypes of them were retained in two China-cultivated garlic groups. Taken together, these results suggest a potential involvement of those candidates in the parallel evolution of garlic bulb organs in two China-cultivated garlic groups. This study provides important insights into the genetic basis of garlic bulb traits and their evolution.


Assuntos
Alho , Estudo de Associação Genômica Ampla , Alho/genética , Alho/crescimento & desenvolvimento , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Fenótipo , Genótipo , Polimorfismo de Nucleotídeo Único/genética , Genoma de Planta/genética
7.
Open Med (Wars) ; 19(1): 20230893, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39221034

RESUMO

Insulin-like growth factor binding protein 2 (IGFBP2) is overexpressed in tumor tissues of several malignancies, including pancreatic cancer. Because of its role in tumor progression, IGFBP2 has been investigated as a tumor biomarker. However, little is known about its utility in pancreatic cancer. Plasma IGFBP2 levels were determined using enzyme-linked immunosorbent assay in 75 patients with pancreatic ductal adenocarcinoma (PDAC), 73 matched healthy controls, and 17 chronic pancreatitis patients. Our results showed that the plasma IGFPB2 level was significantly higher in PDAC patients than in patients with chronic pancreatitis and healthy controls. At a cut-off value of 333.9 ng/mL, the specificity and sensitivity were 78.08 and 65.33%, respectively. IGFBP2 level alone did not outperform carbohydrate antigen 19-9 (CA19-9) in diagnostic accuracy, but it successfully identified 9 out of 24 PDAC patients who were misidentified by CA19-9. The combination of IGFBP2 and CA19-9 was more accurate in the detection of PDAC than CA19-9 alone. IGFBP2 was more accurate than the other in discriminating between chronic pancreatitis and PDAC. Plasma IGFBP2, rather than CA19-9, was higher in the new-onset diabetes, lymph node involvement, and distant metastasis subgroups. IGFBP2 level was notably higher in stage IV cases than in stage I/II or stage III disease. However, CA19-9 did not show a difference between stages. After adjusting for lymph node involvement and distant metastasis, plasma IGFBP2 was identified as an independent prognostic marker for PDAC. The median survival time for patients with an IGFBP2 level ≥333.9 ng/mL was significantly shorter than that for patients with an IGFBP2 level <333.9 ng/mL. Marked elevation of plasma IGFBP2 in PDAC is associated with poorer survival. IGFBP2 may be considered as a supplementary biomarker for the diagnosis and prognostic prediction in Chinese pancreatic cancer patients.

8.
Crit Rev Food Sci Nutr ; : 1-23, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39230393

RESUMO

The increasing emphasis on the quality and safety of agricultural products, which are vital to global trade and consumer health, has driven the innovation of cost-effective, convenient, and rapid smart detection technologies. Smartphones, with their interdisciplinary functionalities, have become valuable tools in quantification and analysis research. Acting as portable, affordable, and user-friendly analytical devices, smartphones are equipped with high-resolution cameras, displays, memory, communication modules, sensors, and operating systems (Android or IOS), making them powerful, palm-sized remote computers. This review delves into how visual inspection technology and smartphones have enhanced the quality and safety of agricultural products over the past decade. It also evaluates the key features and limitations of existing smart rapid inspection methods for agricultural products and anticipates future advancements, offering insights into the application of smart rapid inspection technology in agriculture.

9.
J Genet Genomics ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39241862

RESUMO

Pentatricopeptide repeat (PPR) proteins are a large group of eukaryote-specific RNA-binding proteins that play pivotal roles in plant organelle gene expression. Here, we report the function of PPR21 in mitochondrial intron splicing and its role in maize kernel development. PPR21 is a typical P-type PPR protein targeted to mitochondria. The ppr21 mutants are arrested in embryogenesis and endosperm development, leading to embryo lethality. Null mutations of PPR21 reduce the splicing efficiency of nad2 intron 1, 2, and 4 and impair the assembly and activity of mitochondrial complex I. Previous studies show that the P-type PPR protein EMP12 is required for the splicing of identical introns. However, our protein interaction analyses reveal that PPR21 does not interact with EMP12. Instead, both PPR21 and EMP12 interact with the small MutS-related (SMR) domain-containing PPR protein 1 (PPR-SMR1) and the short P-type PPR protein 2 (SPR2). PPR-SMR1 interacts with SPR2, and both proteins are required for the splicing of many introns in mitochondria, including nad2 intron 1, 2, and 4. These results suggest that a PPR21-(PPR-SMR1/SPR2)-EMP12 complex is involved in the splicing of nad2 introns in maize mitochondria.

11.
Front Vet Sci ; 11: 1410113, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39301284

RESUMO

The pathogenic nature of bacteria can be increased by cleaving antimicrobial peptides using omptins, to avoid or counter the host's natural immune defenses. Plasmid-encoded OmpT (pOmpT or ArlC) in avian pathogenic Escherichia coli (APEC), like the chromosome-encoded OmpT (cOmpT), belongs to the omptin family and both exhibit highly similar sequences and structures. Through sequence alignment and physiological examinations, pOmpT has been identified as a virulence factor, distinct from cOmpT in terms of substrate specificity. When pOmpT is compared with cOmpT regarding their proteolytic activities and target substrates, Asp267 and Ser276 on loop 5 of cOmpT are found to be binding sites that facilitate substrate anchoring and enhance substrate cleavage (protamine or synthetic peptide) by the catalytic center. Conversely, the characteristics of residues at positions 267 and 276 on loop 5 of pOmpT inhibit protamine cleavage, yet allow the specific cleavage of the human antimicrobial peptide RNase 7, which plays a role in host defense. This finding suggests a relationship between these two binding sites and substrate specificity. Furthermore, the substrate-binding sites (residues 267 and 276, particularly residue 267) of cOmpT and pOmpT are determined to be critical in the virulence of APEC. In summary, residues 267 and 276 of pOmpT are crucial for the pathogenicity of APEC and offer new insights into the determinants of APEC virulence and the development of antimicrobial drugs.

12.
Angew Chem Int Ed Engl ; 63(39): e202410123, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39132744

RESUMO

Carbon-based materials have been utilized as effective catalysts for hydrogen peroxide electrosynthesis via two-electron oxygen reduction reaction (2e ORR), however the insufficient selectivity and productivity still hindered the further industrial applications. In this work, we report the Fe-O4 motif activated graphitic carbon material which enabled highly selective H2O2 electrosynthesis operating at high current density with excellent anti-poisoning property. In the bulk production test, the concentration of H2O2 cumulated to 8.6 % in 24 h and the corresponding production rate of 33.5 mol gcat -1 h-1 outperformed all previously reported materials. Theoretical model backed by in situ characterization verified α-C surrounding the Fe-O4 motif as the actual reaction site in terms of thermodynamics and kinetics aspects. The strategy of activating carbon reaction site by metal center via oxo-bridge provides inspiring insights for the rational design of carbon materials for heterogeneous catalysis.

13.
Ecotoxicol Environ Saf ; 284: 116894, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39154500

RESUMO

BACKGROUND: Ambient air pollution might serve as a prognostic factor for ovarian cancer (OC) survival, yet the relationships between plant-based diet indices (PDIs) and OC survival remain unclear. We aimed to investigate the associations of comprehensive air pollution and PDIs with OC survival and explored the effects of air pollution-diet interactions. METHODS: The present study encompassed 658 patients diagnosed with OC. The overall plant-based diet index (PDI), the healthful PDI (hPDI), and the unhealthful PDI (uPDI) were evaluated by a self-reported validated food frequency questionnaire. In addition, an air pollution score (APS) was formulated by summing the concentrations of particulate matter with a diameter of 2.5 microns or less, ozone, and nitrogen dioxide. Cox proportional hazard models were applied to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs). The potential interactions of APS with PDIs in relation to overall survival (OS) were assessed on both multiplicative and additive scales. RESULTS: Throughout a median follow-up of 37.60 (interquartile: 24.77-50.70) months, 123 deaths were confirmed. Comparing to the lowest tertiles, highest uPDI was associated with lower OS of OC (HR = 2.06, 95 % CI = 1.30, 3.28; P-trend < 0.01), whereas no significant associations were found between either overall PDI or hPDI and OC survival. Higher APS (HR for per interquartile range = 1.27, 95 % CI = 1.01, 1.60) was significantly associated with worse OC survival, and the association was exacerbated by adherence to uPDI. Notably, an additive interaction was identified between combined air pollution and uPDI (P < 0.005 for high APS and high uPDI). We also found that adherence to overall PDI aggravated associations of air pollution with OC survival (P-interaction = 0.006). CONCLUSIONS: Joint exposure to various ambient air pollutants was significantly associated with lower survival among patients with OC, particularly for those who predominantly consumed unhealthy plant-based foods.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Neoplasias Ovarianas , Material Particulado , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Neoplasias Ovarianas/mortalidade , Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricos , Material Particulado/análise , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Adulto , Dieta Vegetariana , Modelos de Riscos Proporcionais , Ozônio/análise , Idoso , Dióxido de Nitrogênio/análise , Exposição Ambiental/estatística & dados numéricos , Exposição Ambiental/efeitos adversos , Estudos de Coortes , Dieta Baseada em Plantas
14.
Poult Sci ; 103(10): 104142, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39106694

RESUMO

Avian pathogenic Escherichia coli (APEC) can spread beyond the intestines and cause systemic infections, leading to various clinical manifestations, including airsacculitis, pericarditis, perihepatitis and colisepticemia. The mechanisms facilitating this extraintestinal infections are not fully understood. In this study, we investigate how the tolA gene affects APEC virulence by encoding a protein involved in maintaining outer membrane integrity. We constructed a tolA deletion mutant of APEC strain E058 and evaluated its growth and survival in various environments, including in vitro cultures and in vivo infection models in chickens. We found that the motility-defective ΔtolA mutant exhibits reduced biofilm formation ability and weakened resistance to the environmental stresses, suggesting an important role for TolA in APEC's survival. The lack of tolA gene affects the bacterial ability to resist the host's immune system, such as complement-mediated serum killing or phagocytosis, as shown by the serum killing and macrophage phagocytosis assays. Additionally, in vivo infection studies using chickens demonstrated that the ΔtolA mutant displayed attenuated virulence, evidenced by reduced mortality and lower tissue bacterial burden. Reverse transcription quantitative real-time PCR (RT-qPCR) analysis revealed that inactivation of tolA led to downregulation of virulence genes associated with serum resistance (traT) and flagellar biosynthesis (fliR). Taken together, our findings demonstrate the multifaceted role of TolA protein in promoting the survival, immune evasion, biofilm formation, and virulence of APEC E058. This suggests that targeting TolA could potentially offer new strategies for combating APEC infections.


Assuntos
Biofilmes , Galinhas , Infecções por Escherichia coli , Proteínas de Escherichia coli , Escherichia coli , Doenças das Aves Domésticas , Animais , Doenças das Aves Domésticas/microbiologia , Infecções por Escherichia coli/veterinária , Infecções por Escherichia coli/microbiologia , Virulência , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Escherichia coli/fisiologia , Escherichia coli/patogenicidade , Escherichia coli/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
16.
BMC Genomics ; 25(1): 752, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39090561

RESUMO

Pseudorabies have caused enormous economic losses in China's pig industry and have recurred on many large pig farms since late 2011. The disease is caused by highly pathogenic, antigenic variant pseudorabies virus (vPRV) strains. Our laboratory isolated a pseudorabies virus in 2015 and named it XJ5. The pathogenic ability of this mutant strain was much stronger than that of the original isolate. After we sequenced its whole genome (GenBank accession number: OP512542), we found that its overall structure was not greatly changed compared with that of the previous strain Ea (KX423960.1). The whole genome alignment showed that XJ5 had a strong genetic relationship with the strains isolated in China after 2012 reported in GenBank. Based on the isolation time of XJ5 and the mutation and recombination analysis of programs, we found that the whole genome homology of XJ5 and other strains with Chinese isolates was greater than 95%, while the homology with strains outside Asia was less than 94%, which indicated that there may be some recombination and mutation patterns. We found that virulent PRV isolates emerged successively in China in 2011 and formed two different evolutionary clades from foreign isolates. At the same time, this may be due to improper immunization and the presence of wild strains in the field, and recent reports have confirmed that Bartha vaccine strains recombine with wild strains to obtain new pathogenic strains. We performed genetic evolution analysis of XJ5 isolated and sequenced in our laboratory to trace its possible mutations and recombination. We found that XJ5 may be the result of natural mutation of a virus in a branch of mutant strains widely existing in China.


Assuntos
Evolução Molecular , Genoma Viral , Herpesvirus Suídeo 1 , Mutação , Filogenia , Pseudorraiva , Recombinação Genética , Herpesvirus Suídeo 1/genética , Herpesvirus Suídeo 1/isolamento & purificação , China , Animais , Suínos , Pseudorraiva/virologia , Doenças dos Suínos/virologia , Sequenciamento Completo do Genoma
17.
Natl Sci Rev ; 11(9): nwae069, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39144743

RESUMO

Although magnetism undoubtedly influences life on Earth, the science behind biological magnetic sensing is largely a mystery, and it has proved challenging, especially in the life sciences, to harness the interactions of magnetic fields (MFs) with matter to achieve specific ends. Using the well-established radical pair (RP) mechanism, we here demonstrate a bottom-up strategy for the exploitation of MF effects in living cells by translating knowledge from studies of RP reactions performed in vitro. We found an unprecedented MF dependence of the reactivity of singlet oxygen (1O2) towards electron-rich substrates (S) such as anthracene, lipids and iodide, in which [S ˙+ O2 ˙-] RPs are formed as a basis for MFs influencing molecular redox events in biological systems. The close similarity of the observed MF effects on the biologically relevant process of lipid peroxidation in solution, in membrane mimics and in living cells, shows that MFs can reliably be used to manipulate 1O2-induced cytotoxicity and cell-apoptosis-related protein expression. These findings led to a 'proof-of-concept' study on MF-assisted photodynamic therapy in vivo, highlighting the potential of MFs as a non-invasive tool for controlling cellular events.

18.
Int J Surg ; 110(8): 4716-4726, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39143707

RESUMO

BACKGROUND: In recent years, the widespread use of lipid-lowering drugs, especially statins, has attracted people's attention. Statin use may be potentially associated with a reduced risk of breast cancer. OBJECTIVE: To explore the relationship between statin use and cancer risk. And further explore the potential role of statins in the adjuvant treatment of breast cancer. METHODS: Data for the Mendelian randomization portion of the study were obtained from genome-wide association studies of common cancers in the UK Biobank and FinnGen studies and from the Global Lipid Genetics Consortium's low density lipoprotein (LDL). In addition, the impacts of statins and chemotherapy drugs on breast cancer were examined using both in vitro and in vivo models, with particular attention to the expression levels of the immune checkpoint protein PD-L1 and its potential to suppress tumor growth. RESULTS: Data from about 3.8 million cancer patients and ~1.3 million LDL-measuring individuals were analyzed. Genetically proxied HMGCR inhibition (statins) was associated with breast cancer risk reduction (P=0.0005). In vitro experiments showed that lovastatin significantly inhibited paclitaxel-induced PD-L1 expression and assisted paclitaxel in suppressing tumor cell growth. Furthermore, the combination therapy involving lovastatin and paclitaxel amplified CD8+ T-cell infiltration, bolstering their tumor-killing capacity and enhancing in vivo efficacy. CONCLUSION: The utilization of statins is correlated with improved prognoses for breast cancer patients and may play a role in facilitating the transition from cold to hot tumors. Combination therapy with lovastatin and paclitaxel enhances CD8+ T-cell activity and leads to better prognostic characteristics.


Assuntos
Antígeno B7-H1 , Neoplasias da Mama , Linfócitos T CD8-Positivos , Inibidores de Hidroximetilglutaril-CoA Redutases , Paclitaxel , Neoplasias da Mama/tratamento farmacológico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/metabolismo , Feminino , Paclitaxel/farmacologia , Paclitaxel/administração & dosagem , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Prognóstico , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Camundongos , Animais , Lovastatina/farmacologia , Lovastatina/administração & dosagem , Estudo de Associação Genômica Ampla
19.
Phys Chem Chem Phys ; 26(35): 23144-23151, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39189163

RESUMO

In this paper, we innovatively stack multiple resonant units of photoconductive silicon to design an ultra-broadband metamaterial absorber. By manipulating the conductivity of the silicon with a pump beam, adjustments are made to the amplitude of the wide absorption spectrum spanning 6.6 THz, enabling functional switching from total reflection to near-perfect ultra-broadband absorption. By integrating vanadium dioxide as an intermediary layer, a dual-mode switchable absorber is realized, offering dual control functionalities. Temperature changes enable the absorber to switch between dual-band absorption and ultra-broadband absorption, while variations in pump beam intensity allow for further amplitude adjustments within the absorption spectrum. Impedance matching theory and near-field analysis provide the necessary physical foundation for understanding broadband absorption. Structural parameters, incident angle, and polarization angle of the incident electromagnetic waves are also studied to demonstrate the device's robustness. Our proposed absorbers not only greatly broaden the absorption bandwidth of silicon-based absorbers, but also offer versatility, polarization insensitivity, and robustness over a wide range of incidence angles. Moreover, our design ideas are useful for broadening the bandwidth and enhancing absorption, which enables wider applications in ultra-broadband terahertz absorption and promises extensive prospects.

20.
Biomolecules ; 14(8)2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39199378

RESUMO

BACKGROUND: Accumulating evidence indicates that PSAT1 not only reprogrammed metabolic function but also exhibits "moonlighting" functions in promoting tumor malignancy. However, the underlying molecular mechanisms of PSAT1 promoting ER-negative breast cancer cell migration need further investigation. METHODS: Briefly, the PSAT1 and ITGA2 expression in cells and tissues was detected using qRT-PCR, immunofluorescence staining and western blot assay. The effect of PSAT1 and ITGA2 was verified both in vitro and in vivo. RNA-seq analysis explored a series of differently expressed genes. The regulation between SP1 and ITGA2 was investigated by ChIP analysis. RESULTS: We reported PSAT1 was highly expressed in ER-breast cancer tissues and tumor cells and positively correlated with metastasis. Moreover, RNA-seq analysis explored a series of differently expressed genes, including ITGA2, in PSAT1 overexpressed cells. Mechanistically, PSAT1 facilitated breast cancer metastasis via the p-AKT/SP1/ITGA2 axis. We further elucidated that PSAT1 promoted the entry of SP1 into the nucleus through the upregulation of p-AKT and confirmed ITGA2 is a target of SP1. In addition, enhanced cell migration was remarkably reversed by ITGA2 depletion or p-AKT inhibitor treatment. CONCLUSION: This study clarified the mechanism of PSAT1 in promoting ER-negative breast cancer metastasis, which may provide mechanistic clues for attenuating breast cancer metastasis.


Assuntos
Neoplasias da Mama , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Integrina alfa2 , Metástase Neoplásica , Proteínas Proto-Oncogênicas c-akt , Fator de Transcrição Sp1 , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Integrina alfa2/metabolismo , Integrina alfa2/genética , Células MCF-7 , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Estrogênio/genética , Transdução de Sinais , Fator de Transcrição Sp1/metabolismo , Fator de Transcrição Sp1/genética
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