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1.
Materials (Basel) ; 17(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39274625

RESUMO

Al-Mg alloys are widely used as important engineering structural materials in aerospace engineering, transportation systems, and structural constructions due to their low density, high specific strength, corrosion resistance, welding capability, fatigue strength, and cost-effectiveness. However, the conventional Al-Mg alloys can no longer fully satisfy the demands of practical production due to difficulties caused by many defects. The high strength of Al-Mg alloys as non-heat treatment precipitation-strengthened alloys is achieved primarily by solid solution strengthening along with work hardening rather than precipitation strengthening. Therefore, severe plastic deformation (SPD) techniques can be often used to produce ultrafine-grained structures to fabricate ultra-high strength aluminum alloys. However, this approach often achieves the strengthening of material at the cost of reduced ductility. This paper comprehensively summarizes the various approaches of ultrafine/nanocrystalline materials for enhancing their plasticity, elaborates on the creation of a bimodal microstructure within the alloy, and discusses the formation of a nanotwin microstructure within the alloy and the incorporation of dispersed nanoparticles. The mechanisms underlying both the strengthening and toughening during large plastic deformation in aluminum alloys are summarized, and the future research direction of high-performance ultrafine crystalline and nanocrystalline Al-Mg aluminum alloys is prospected.

2.
Org Lett ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39259671

RESUMO

We report a novel visible-light-driven photoredox-catalyzed cascade reaction involving Conia-ene-type cyclization and Smiles rearrangement initiated from alkyne-tethered α-sulfonyl esters. This methodology not only facilitates the rapid synthesis of a broad spectrum of highly substituted methylenecarbocycles but also introduces a new mechanistic pathway with aryl group migration, surpassing the conventional 1,5-hydrogen shift typically observed in Conia-ene reactions.

3.
Bioinformatics ; 40(Suppl 2): ii120-ii127, 2024 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-39230705

RESUMO

MOTIVATION: Learning cellular dynamics through reconstruction of the underlying cellular potential energy landscape (aka Waddington landscape) from time-series single-cell RNA sequencing (scRNA-seq) data is a current challenge. Prevailing data-driven computational methods can be hampered by the lack of physical principles to guide learning from complex data, resulting in reduced prediction accuracy and interpretability when applied to infer cell population dynamics. RESULTS: Here, we propose PI-SDE, a physics-informed neural stochastic differential equation (SDE) framework that combines the Hamilton-Jacobi (HJ) equation and neural SDE to learn cellular dynamics. Grounded in potential energy theory of biological systems, PI-SDE integrates the principle of least action by enforcing the HJ equation when reconstructing cellular potential energy function. This approach not only facilitates accurate predictions, but also improves interpretability, especially in the reconstructed potential energy landscape. Through benchmarking on two real scRNA-seq datasets, we demonstrate the importance of incorporating the HJ regularization term in dynamic inference, especially in predicting gene expression at held-out time points. Meanwhile, the learned potential energy landscape provides biologically interpretable insights into the process of cell differentiation. Our framework enhances model performance, while maintaining robustness and stability. AVAILABILITY: PI-SDE software is available at https://github.com/QiJiang-QJ/PI-SDE.


Assuntos
Análise de Célula Única , Análise de Célula Única/métodos , Redes Neurais de Computação , Análise de Sequência de RNA/métodos , Humanos , RNA-Seq/métodos , Biologia Computacional/métodos , Algoritmos , Análise da Expressão Gênica de Célula Única
4.
Virol Sin ; 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39233140

RESUMO

Influenza B viruses (IBVs) primarily infect humans and are a common cause of respiratory infections in humans. Here, to systematically analyze the antigenicity of the IBVs Hemagglutinin (HA) protein, 31 B/Victoria and 19 B/Yamagata representative circulating strains were selected from Global Initiative of Sharing All Influenza Data (GISAID), and pseudotyped viruses were constructed with the vesicular stomatitis virus system. Guinea pigs were immunized with three doses of vaccines (one dose of DNA vaccines following two doses of pseudotyped virus vaccines) of the seven IBV vaccine strains, and neutralizing antibodies against the pseudotyped viruses were tested. By comparing differences between various vaccine strains, we constructed several pseudotyped viruses that contained various mutations based on vaccine strain BV-21. The vaccine strains showed good neutralization levels against the epidemic virus strains of the same year, with neutralization titers ranging from 370 to 840, while the level of neutralization against viruses prevalent in previous years decreased 1-10-fold. Each of the high-frequency epidemic strains of B/Victoria and B/Yamagata not only induced high neutralizing titers, but also had broadly neutralizing effects against virus strains of different years, with neutralizing titers ranging from 1000 to 7200. R141G, D197N, and R203K were identified as affecting the antigenicity of IBV. In this study, pseudotyped virus system was used to monitor the cross-neutralizing efficacy of high-frequency epidemic strains and vaccine strains recommended by the World Health Organization. Additionally, we identified three mutation sites that can seriously affect the antigenicity of B/Victoria vaccine strains. These mutation sites provide valuable references for the selection and design of a universal IBV vaccine strain in the future.

5.
Chem Biol Interact ; 403: 111221, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39233264

RESUMO

Exosomes play a crucial role in regulating extracellular communication between normal and cancer cells within the tumor microenvironment, thereby affecting tumor progression through their cargo molecules. However, the specific impact of exosomal circular RNAs (circRNAs) on the development of cadmium-induced carcinogenesis remains unclear. To address this, we investigated whether exosomes derived from normal human bronchial epithelial BEAS-2B (N-B2B) cells could transmit circRNA to cadmium-transformed BEAS-2B (Cd-B2B) cells and the potential effects on Cd-B2B cells. Our findings demonstrated a significant downregulation of circ_0004664 in Cd-B2B cells compared to N-B2B cells (P < 0.01). Overexpression of circ_0004664 in Cd-B2B cells led to a significant inhibition of cell migration and invasion (P < 0.01 or P < 0.05). Furthermore, N-B2B cells could transfer circ_0004664 into recipient Cd-B2B cells via exosomes, subsequently inhibiting cell migration and invasion (P < 0.05 or P < 0.01). Mechanistic investigations revealed that exosomal circ_0004664 functioned as a competitive endogenous RNA for miR-942-5p, resulting in an upregulation of PTEN (P < 0.05). Our study highlights the involvement of exosomal circ_0004664 in cell-cell communication during cadmium carcinogenesis, providing a novel insight into the role of exosomal circRNA in this process.

6.
Nucleic Acids Res ; 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39119904

RESUMO

Quantitative PCR (qPCR) is the gold standard for detection and quantitation of known DNA targets, but the scarcity of spectrally distinct fluorophores and filter sets limits the number of detectable targets. Here, we introduce color cycle multiplex amplification (CCMA) to significantly increase the number of detectable DNA targets in a single qPCR reaction using standard instrumentation. In CCMA, presence of one DNA target species results in a pre-programmed pattern of fluorescence increases. This pattern is distinguished by cycle thresholds (Cts) through rationally designed delays in amplification. For example, we design an assay wherein Staphylococcus aureus sequentially induces FAM, then Cy5.5, then ROX fluorescence increases with more than 3 cycles between each signal. CCMA offers notably higher potential for multiplexing because it uses fluorescence permutation rather than combination. With 4 distinct fluorescence colors, CCMA theoretically allows the detection of up to 136 distinct DNA target sequences using fluorescence permutation. Experimentally, we demonstrated a single-tube qPCR assay screening 21 sepsis-related bacterial DNA targets in samples of blood, sputum, pleural effusion and bronchoalveolar lavage fluid, with 89% clinical sensitivity and 100% clinical specificity, showing its potential as a powerful tool for advanced quantitative screening in molecular diagnostics.

7.
Nat Commun ; 15(1): 6679, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39107265

RESUMO

The efficiency and stability of perovskite module devices are mainly limited by the quality of scalable perovskite films and sub-cells' lateral contact. Here, firstly, we report constant low temperature substrate to regulate the growth of perovskite intermediate films to slow down the crystallization for obtaining high-quality homogeneous perovskite films in large scale size, which avoid the effect of the ambient temperature on the film quality. Secondly, a scribing step named P1.5 was added before the top function layers deposition, the diffusion barrier layer can be formed "naturally" at the interconnection interface without introducing any additional materials, which well alleviates the diffusion degradation process. As a result, our inverted perovskite devices exhibit a very small efficiency loss with area expansion comparable to other photovoltaic devices (for example, Cadmium Telluride), the perovskite module (aperture area 14.61 cm2) shows a certified quasi-steady-state power conversion efficiency of 22.73%, and the module maintaining over 90% of its initial efficiency after 1000 hours of continuous operation under illumination.

8.
Heliyon ; 10(14): e34722, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39130420

RESUMO

Nano-TiO2 is widely used in various fields such as industry, daily necessities, food and medicine. Previous studies have shown that it can enter mammalian tissues through the digestive tract or respiratory tract and have effects on various organs and systems. However, the effect of nano-TiO2 on the mammalian thyroid gland has not been reported. In this study, we fed SD rats with rutile nano-TiO2 at a dose of 5 mg/kg body weight for 3 weeks, and then examined the thyroid histology and thyroid function of the rats. In vitro experiments were conducted to determine the effects of nano-TiO2 on the viability, apoptosis, inflammatory factors, antioxidant enzymes, and oxidative stress of human thyroid follicular epithelial cells. Histological evidence showed abnormal morphology of rat thyroid follicles and organelle damage in follicular epithelial cells. Nano-TiO2 caused a decrease in the level of sodium/iodide symporter (NIS), an increase in the level of apoptotic protein cleaved-caspase 3, and an increase in the levels of pro-inflammatory factors IL-1ß and TNF-α in rat thyroid tissue. Nano-TiO2 also resulted in increased serum FT4 and TPO-Ab levels. In in vitro experiments, nano-TiO2 reduced the viability of human thyroid follicular cells, downregulated the levels and activities of antioxidant enzymes CAT, GPX1 and SOD, and increased the levels of ROS and MDA caused by oxidative stress. These results indicate that nano-TiO2 damages the structure and function of thyroid follicular epithelial cells through oxidative stress. Long-term exposure to nano-TiO2 could be a potential risk factor for thyroid dysfunction.

9.
BMC Cancer ; 24(1): 985, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39123182

RESUMO

BACKGROUND: In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). METHODS: Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. RESULTS: Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). CONCLUSIONS: Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas , Micro-Ondas , Veia Porta , Ablação por Radiofrequência , Humanos , Hepatectomia/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirurgia , Quimioembolização Terapêutica/métodos , Ablação por Radiofrequência/métodos , Micro-Ondas/uso terapêutico , Estudos Retrospectivos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirurgia , Idoso , Adulto , Fígado/cirurgia , Fígado/irrigação sanguínea , Embolização Terapêutica/métodos , Resultado do Tratamento , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Taxa de Sobrevida , China/epidemiologia , Terapia Combinada
10.
J Enzyme Inhib Med Chem ; 39(1): 2390909, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39206852

RESUMO

An oxidising and substituting one-pot reaction strategy has been developed to synthesise dihydromyricetin derivatives with the aim of enhancing the inhibitory activity of dihydromyricetin against SARS-CoV-2. Different ω-methoxy-ω-oxeylkyl was introduced in C7-OH site and yielded eight analogs, all of them showed good inhibitory activity against SARS-CoV-2 3CLpro with IC50 values ranging from 0.72 to 2.36 µM. In the Vero E6-cell, compound 3 has a good activity of anti-SARS-CoV-2 virus (Omicron virus BA.5) in the prevention model, with an EC50 of 15.84 µM, and so do compound 10 in the therapeutic model, with an EC50 of 11.52 µM. The results suggest that the introduction of long chain ω-oxeylkyl at C7-OH facilitate the inhibition of viral replication in the therapeutic model, which is consistent with the binding energies predicted from molecular docking conclusions. It implies that dihydromyricetin derivatives have the potential to become effective inhibitors of SARS-CoV-2 Omicron and other viruses.


Assuntos
Antivirais , Desenho de Fármacos , Flavonóis , SARS-CoV-2 , Antivirais/farmacologia , Antivirais/síntese química , Antivirais/química , Chlorocebus aethiops , SARS-CoV-2/efeitos dos fármacos , Células Vero , Flavonóis/farmacologia , Flavonóis/síntese química , Flavonóis/química , Animais , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Replicação Viral/efeitos dos fármacos , Estrutura Molecular , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , Humanos
11.
Zhonghua Nan Ke Xue ; 30(4): 300-305, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-39210415

RESUMO

OBJECTIVE: To investigate the application value of ultrasound technology in transurethral enucleation and resection of the prostate (TUERP). METHODS: This study included 78 BPH patients admitted in our hospital from June 2021 to June 2023, aged 70.68±8.63 years and with the indication of surgery. We randomly divided them into two groups to receive TUERP (the control group, n = 39) and ultrasound-assisted TUERP (the US-TUERP group, n = 39). We statistically analyzed and compared the relevant parameters obtained before and after operation between the two groups. RESULTS: No statistically significant differences were observed in the operation time and bladder irrigation time between the two groups (P > 0.05). More glandular tissues were removed but less intraoperative bleeding and fewer perioperative complications occurred in the US-TUERP group than in the control. Compared with the baseline, IPSS, postvoid residual urine volume (PVR), quality of life score (QOL) and maximum urinary flow rate (Qmax) were significantly improved in both groups at 1 and 3 months after surgery, even more significantly in the US-TUERP than in the control group (P < 0.05). CONCLUSION: US-TUERP helps achieve complete resection of the hyperplastic prostatic tissue along the surgical capsule at the anatomical level, with a higher safety, fewer perioperative complications, and better therapeutic effects.


Assuntos
Próstata , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Ultrassonografia , Humanos , Masculino , Ressecção Transuretral da Próstata/métodos , Idoso , Hiperplasia Prostática/cirurgia , Próstata/cirurgia , Qualidade de Vida , Resultado do Tratamento , Duração da Cirurgia
12.
IEEE Trans Image Process ; 33: 4568-4583, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39150807

RESUMO

High-quality panoramic images with a Field of View (FoV) of 360° are essential for contemporary panoramic computer vision tasks. However, conventional imaging systems come with sophisticated lens designs and heavy optical components. This disqualifies their usage in many mobile and wearable applications where thin and portable, minimalist imaging systems are desired. In this paper, we propose a Panoramic Computational Imaging Engine (PCIE) to achieve minimalist and high-quality panoramic imaging. With less than three spherical lenses, a Minimalist Panoramic Imaging Prototype (MPIP) is constructed based on the design of the Panoramic Annular Lens (PAL), but with low-quality imaging results due to aberrations and small image plane size. We propose two pipelines, i.e. Aberration Correction (AC) and Super-Resolution and Aberration Correction (SR&AC), to solve the image quality problems of MPIP, with imaging sensors of small and large pixel size, respectively. To leverage the prior information of the optical system, we propose a Point Spread Function (PSF) representation method to produce a PSF map as an additional modality. A PSF-aware Aberration-image Recovery Transformer (PART) is designed as a universal network for the two pipelines, in which the self-attention calculation and feature extraction are guided by the PSF map. We train PART on synthetic image pairs from simulation and put forward the PALHQ dataset to fill the gap of real-world high-quality PAL images for low-level vision. A comprehensive variety of experiments on synthetic and real-world benchmarks demonstrates the impressive imaging results of PCIE and the effectiveness of the PSF representation. We further deliver heuristic experimental findings for minimalist and high-quality panoramic imaging, in terms of the choices of prototype and pipeline, network architecture, training strategies, and dataset construction. Our dataset and code will be available at https://github.com/zju-jiangqi/PCIE-PART.

13.
Sci Rep ; 14(1): 18738, 2024 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-39134566

RESUMO

To evaluate the impact of neoadjuvant chemotherapy on perioperative immune function in breast cancer patients, focusing on CD3+, CD4+, CD8+, and natural killer (NK) cells, as well as the CD4+/CD8+ ratio. We retrospectively reviewed medical records of breast cancer patients who underwent surgery with or without neoadjuvant chemotherapy at our medical center from January 2020 to December 2022. Patients were matched 1:1 based on propensity scores. Immune cell proportions and the CD4+/CD8+ ratio were compared on preoperative day one and postoperative days one and seven. Among matched patients, immune cell proportions and the CD4+/CD8+ ratio did not significantly differ between those who received neoadjuvant chemotherapy and those who did not at any of the three time points. Similar results were observed in chemotherapy-sensitive patients compared to the entire group of patients who did not receive neoadjuvant chemotherapy. However, chemotherapy-insensitive patients had significantly lower proportions of CD4+ and NK cells, as well as a lower CD4+/CD8+ ratio, at all three time points compared to patients who did not receive neoadjuvant chemotherapy. Neoadjuvant chemotherapy may impair immune function in chemotherapy-insensitive patients, but not in those who are sensitive to the treatment.


Assuntos
Neoplasias da Mama , Células Matadoras Naturais , Terapia Neoadjuvante , Pontuação de Propensão , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Neoplasias da Mama/cirurgia , Feminino , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Pessoa de Meia-Idade , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Adulto , Idoso , Período Perioperatório , Relação CD4-CD8 , Quimioterapia Adjuvante/métodos
14.
World J Gastroenterol ; 30(27): 3304-3313, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39086752

RESUMO

BACKGROUND: The efficacy of Vonoprazan-amoxicillin dual therapy (VAT) in the treatment of Helicobacter pylori (H. pylori) is controversial. AIM: To evaluate the efficacy of VAT in the Chinese population. METHODS: This prospective, multicenter, randomized, open-label, and two-stage study was conducted at 23 centers in Fujian, China (May 2021-April 2022). H. pylori-infected patients were randomized to bismuth quadruple therapy (BQT), BQT-Vonoprazan (BQT-V), seven-day VAT (VAT-7), ten-day VAT (VAT-10), and fourteen-day VAT (VAT-14) groups. The primary endpoint was the H. pylori eradication rate. The secondary endpoint was the frequency of adverse events. This study was registered with the Chinese Clinical Trial Registry, ChiCTR2100045778. RESULTS: In the first stage, VAT-7 and BQT-V groups were selected for early termination because less than 23 among 28 cases were eradicated. In the second stage, the eradication rates for BQT, VAT-10, and VA-14 were 80.2% [95% confidence interval (95%CI): 71.4%-86.8%], 93.2% (86.6%-96.7%), 92.2% (85.3%-96.0%) in the intention-to-treat (ITT) analysis, and 80.9% (95%CI: 71.7%-87.5%), 94.0% (87.5%-97.2%), and 93.9% (87.4%-97.2%) in the per-protocol analysis. The ITT analysis showed a higher eradication rate in the VAT-10 and VAT-14 groups than in the BQT group (P = 0.022 and P = 0.046, respectively). The incidence of adverse events in the VAT-10 and VAT-14 groups was lower than in the BQT group (25.27% and 13.73% vs 37.62%, respectively; P < 0.001). CONCLUSION: VAT with a duration of 10 or 14 days achieves a higher eradication rate than the BQT, with a more tolerable safety profile in H. pylori-infected patients in Fujian.


Assuntos
Amoxicilina , Antibacterianos , Quimioterapia Combinada , Infecções por Helicobacter , Helicobacter pylori , Inibidores da Bomba de Prótons , Pirróis , Sulfonamidas , Humanos , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/diagnóstico , Pessoa de Meia-Idade , Masculino , Sulfonamidas/efeitos adversos , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/isolamento & purificação , Feminino , Estudos Prospectivos , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Amoxicilina/uso terapêutico , China/epidemiologia , Quimioterapia Combinada/métodos , Pirróis/uso terapêutico , Pirróis/efeitos adversos , Pirróis/administração & dosagem , Resultado do Tratamento , Adulto , Inibidores da Bomba de Prótons/uso terapêutico , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Antibacterianos/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Idoso , População do Leste Asiático
15.
Int Immunopharmacol ; 140: 112728, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39098227

RESUMO

Imatinib-induced skin rash poses a significant challenge for patients with gastrointestinal stromal tumor, often resulting in treatment interruption or discontinuation and subsequent treatment failure. However, the underlying mechanism of imatinib-induced skin rashes in gastrointestinal stromal tumor patients remains unclear. A total of 51 patients (27 with rash and 24 without rash) were enrolled in our study. Blood samples were collected concomitantly with the onset of clinical manifestations of rashes, and simultaneously collecting clinical relevant information. The imatinib concentration and untargeted metabolomics were performed by ultra-high-performance liquid chromatography-tandem mass spectrometry. There were no significant differences in age, gender, imatinib concentration and white blood cells count between the rash group and the control group. However, the rash group exhibited a higher eosinophil count (P<0.05) and lower lymphocyte count (P<0.05) compared to the control group. Untargeted metabolomics analysis found that 105 metabolites were significantly differentially abundant. The univariate analysis highlighted erucamide, linoleoylcarnitine, and valine betaine as potential predictive markers (AUC≥0.80). Further enriched pathway analysis revealed primary metabolic pathways, including sphingolipid signaling pathway, sphingolipid metabolism, cysteine and methionine metabolism, biosynthesis of unsaturated fatty acids, arginine and proline metabolism, and biosynthesis of amino acids. These findings suggest that the selected differential metabolites could serve as a foundation for the prediction and management of imatinib-induced skin rash in gastrointestinal stromal tumor patients.


Assuntos
Antineoplásicos , Exantema , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Mesilato de Imatinib , Metabolômica , Humanos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Exantema/induzido quimicamente , Neoplasias Gastrointestinais/tratamento farmacológico , Idoso , Adulto
16.
Emerg Microbes Infect ; 13(1): 2399273, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39207222

RESUMO

The incidence of tuberculosis (TB) has declined more slowly in rural than urban areas in China, and data on the patterns of transmission and the high-risk populations in rural areas remains scarce. We conducted a population-based study of culture-positive pulmonary TB patients diagnosed in rural Linzhou City, Henan Province from July 2018 to February 2023. Genomic clusters were defined based on whole-genome sequencing and risk factors for clustering were identified by logistic regression. Transmission events were inferred with phybreak and transmission links were sought through epidemiological investigation of clustered patients. Logistic regression was used to explore the relationship between genomic differences of patient isolates and geographical distances of patient residences. Spatial hotspots were defined using kernel density estimation. Of 455 culture-positive patients, 430 were included in the final analysis. Overall, 192 (44.7%,192/430) patients were grouped into 49 clusters. Clusters containing ≥5 patients accounted for 18.4% (9/49) of the clusters and clustering was highest in student patients. No super-spreaders were detected. Confirmed epidemiologic links were identified for only 18.2% of clustered patients. The clustering risk decreased rapidly with increasing distances between patient residences, but 77.6% of clustered patient pairs lived ≥5.0 km apart. Both the Central Subdistrict and Rencun Township were identified as hotspots for TB transmission. Recent transmission appears to be an important driver of the TB burden in Linzhou. The formulation of effective strategies to reduce TB incidence in rural areas will require further studies to identify high-risk populations and venues where local inhabitants congregate and transmit the infection.


Assuntos
Mycobacterium tuberculosis , População Rural , Humanos , China/epidemiologia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Mycobacterium tuberculosis/classificação , Estudos Prospectivos , Adulto Jovem , Fatores de Risco , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/transmissão , Tuberculose Pulmonar/microbiologia , Sequenciamento Completo do Genoma , Incidência , Idoso , Adolescente , Análise por Conglomerados , Tuberculose/epidemiologia , Tuberculose/transmissão , Tuberculose/microbiologia
17.
Transl Oncol ; 49: 102068, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39121828

RESUMO

OBJECTIVE: Nucleotide metabolic reprogramming as a hallmark of cancer is closely related to the occurrence and progression of cancer. We aimed to comprehensively analyze the nucleotide metabolism-related gene set and clinical significance in gliomas. METHODS: The RNA sequencing data of 702 gliomas from the Cancer Genome Atlas (TCGA) dataset were included as the training set, and the RNA sequencing data from the other three datasets (CGGA, GSE16011, and Rembrandt) were used as independent validation sets. Survival curve, Cox regression analysis, time-dependent ROC curve and nomogram model were performed to evaluate prognostic power of signature. R language was the main tool for bioinformatic analysis and graphical work. RESULTS: Based on the expression profiles of nucleotide metabolism-related genes, consensus clustering identified two robust clusters with different prognosis. We then developed a nucleotide metabolism-related signature that was closely related to clinical, pathological, and genomic characteristics of gliomas. And ROC curve showed that our signature was a potential biomarker for mesenchymal subtype. Survival curve and Cox regression analysis revealed signature as an independent prognostic factor for gliomas. In addition, we constructed a nomogram model to predict individual survival. Finally, functional analysis showed that nucleotide metabolism not only affected cell division and cell cycle, but also was associated with immune response in gliomas. CONCLUSION: We developed a nucleotide metabolism-related signature to predict prognosis and provided new insights into the role of nucleotide metabolism in gliomas.

18.
Cancer Lett ; 601: 217149, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39117066

RESUMO

Understanding the determinants of long-term liver metastasis (LM) outcomes in gastrointestinal stromal tumor (GIST) patients is crucial. We established the feature selection model of intratumoral microbiome at the surgery, achieving robust predictive accuracies of 0.953 and 0.897 AUCs in discovery (n = 74) and validation (n = 34) cohorts, respectively. Notably, despite the significant reduction in LM occurrence with adjuvant imatinib (AI) treatment, intratumoral microbiome exerted independently stronger effects on post-operative LM. Employing both 16S and full-length rRNA sequencing, we pinpoint intracellular Shewanella algae as a foremost LM risk factor in both AI- and non-AI-treated patients. Experimental validation confirmed S. algae's intratumoral presence in GIST, along with migration/invasion-promoting effects on GIST cells. Furthermore, S. algae promoted LM and impeded AI treatment in metastatic mouse models. Our findings advocate for incorporating intratumoral microbiome evaluation at surgery, and propose S. algae as a therapeutic target for LM suppression in GIST.


Assuntos
Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Mesilato de Imatinib , Neoplasias Hepáticas , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/microbiologia , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/microbiologia , Animais , Camundongos , Feminino , Masculino , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/microbiologia , Quimioterapia Adjuvante/métodos , Pessoa de Meia-Idade , Microbiota/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Idoso
19.
Clin Exp Med ; 24(1): 177, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105936

RESUMO

Coagulation disorders are common in Kawasaki disease (KD). The main objectives of the present study were to probe the associations of coagulation profiles with clinical classification, IVIG responsiveness, coronary artery abnormalities (CAAs) in the acute episode of KD. A total of 313 KD children were recruited and divided into six subgroups, including complete KD (n = 217), incomplete KD (n = 96), IVIG-responsive KD (n = 293), IVIG-nonresponsive KD (n = 20), coronary artery noninvolvement KD (n = 284) and coronary artery involvement KD (n = 29). Blood samples were collected within 24-h pre-IVIG therapy and 48-h post-IVIG therapy. Coagulation profiles, conventional inflammatory mediators and blood cell counts were detected. Echocardiography was performed during the period from 2- to 14-day post-IVIG infusion. In addition, 315 sex- and age-matched healthy children were enrolled as the controls. (1) Before IVIG therapy, coagulation disorders were more prone to appear in KD patients than in healthy controls, and could be overcome by IVIG therapy. FIB and DD significantly increased in the acute phase of KD, whereas reduced to normal levels after IVIG therapy. (2) PT and APTT were significantly longer in patients with complete KD when compared with their incomplete counterparts after IVIG therapy. (3) The larger δDD, δFDP and the smaller δPT, δINR predicted IVIG nonresponsiveness. (4) The higher δDD and δFDP correlated with a higher risk for CAAs (DD: r = -0.72, FDP: r = -0.54). Coagulation disorders are correlated with complete phenotype, IVIG nonresponsiveness and CAA occurrence in the acute episode of KD, and can be rectified by synergistic effects of IVIG and aspirin.


Assuntos
Imunoglobulinas Intravenosas , Síndrome de Linfonodos Mucocutâneos , Humanos , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/sangue , Síndrome de Linfonodos Mucocutâneos/complicações , Imunoglobulinas Intravenosas/uso terapêutico , Masculino , Feminino , Pré-Escolar , Lactente , Criança , Vasos Coronários/patologia , Vasos Coronários/diagnóstico por imagem , Ecocardiografia , Coagulação Sanguínea/efeitos dos fármacos , Resultado do Tratamento , Transtornos da Coagulação Sanguínea/tratamento farmacológico , Transtornos da Coagulação Sanguínea/etiologia , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/tratamento farmacológico
20.
Int J Biol Macromol ; 277(Pt 2): 134231, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39074699

RESUMO

To investigate the impact of chlorantraniliprole on Procambarus clarkii, acute toxicity tests were performed. Results indicated that 96 h post-exposure to chlorantraniliprole (60 mg/L) led to the separation of the hepatopancreas basement membrane, causing cell swelling, rupture, and vacuolation. Moreover, acid phosphatase (ACP) and alkaline phosphatase (AKP) activities exhibited divergent trends across four concentrations of chlorantraniliprole (0, 30, 60, and 90 mg/L). Hydrogen peroxide (H2O2) and catalase (CAT) levels significantly increased, while total superoxide dismutase (T-SOD) and malonaldehyde (MDA) activities decreased, indicating oxidative stress in the hepatopancreas. A total of 276 differentially expressed genes (DEGs) were identified, with 204 up-regulated and 72 down-regulated. Out of these, 114 DEGs were successfully annotated and classified into 99 pathways, with a primary focus on the cytochrome P450-mediated xenobiotic metabolism pathway. The DEGs enriched in this pathway, along with transcriptome data, were validated using quantitative-polymerase chain reaction. This study enhances the transcriptome database of P. clarkii and provides fundamental insights into its immune defense and antioxidant mechanisms. Additionally, it lays a theoretical foundation for future research on disease prevention in P. clarkii within rice-shrimp culture systems.


Assuntos
Sistema Enzimático do Citocromo P-450 , Xenobióticos , ortoaminobenzoatos , Animais , ortoaminobenzoatos/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Xenobióticos/metabolismo , Inativação Metabólica/genética , Astacoidea/genética , Astacoidea/efeitos dos fármacos , Astacoidea/metabolismo , Transcriptoma/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Perfilação da Expressão Gênica , Hepatopâncreas/metabolismo , Hepatopâncreas/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos
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