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1.
Front Endocrinol (Lausanne) ; 15: 1342204, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948513

RESUMO

Purpose: Chest computed tomography (CT) is used to determine the severity of COVID-19 pneumonia, and pneumonia is associated with hyponatremia. This study aims to explore the predictive value of the semi-quantitative CT visual score for hyponatremia in patients with COVID-19 to provide a reference for clinical practice. Methods: In this cross-sectional study, 343 patients with RT-PCR confirmed COVID-19, all patients underwent CT, and the severity of lung lesions was scored by radiologists using the semi-quantitative CT visual score. The risk factors of hyponatremia in COVID-19 patients were analyzed and combined with laboratory tests. The thyroid function changes caused by SARS-CoV-2 infection and their interaction with hyponatremia were also analyzed. Results: In patients with SARS-CoV-2 infection, the total severity score (TSS) of hyponatremia was higher [M(range), 3.5(2.5-5.5) vs 3.0(2.0-4.5) scores, P=0.001], implying that patients with hyponatremia had more severe lung lesions. The risk factors of hyponatremia in the multivariate regression model included age, vomiting, neutrophils, platelet, and total severity score. SARS-CoV-2 infection impacted thyroid function, and patients with hyponatremia showed a lower free triiodothyronine (3.1 ± 0.9 vs 3.7 ± 0.9, P=0.001) and thyroid stimulating hormone level [1.4(0.8-2.4) vs 2.2(1.2-3.4), P=0.038]. Conclusion: Semi-quantitative CT score can be used as a risk factor for hyponatremia in patients with COVID-19. There is a weak positive correlation between serum sodium and free triiodothyronine in patients with SARS-CoV-2 infection.


Assuntos
COVID-19 , Hiponatremia , SARS-CoV-2 , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , Humanos , COVID-19/complicações , COVID-19/diagnóstico por imagem , Hiponatremia/etiologia , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Tomografia Computadorizada por Raios X/métodos , Idoso , Adulto , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico por imagem , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico por imagem , Pandemias , Betacoronavirus , Idoso de 80 Anos ou mais
2.
Front Med (Lausanne) ; 11: 1408297, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38947239

RESUMO

Background: Type 1 diabetes mellitus (T1DM) is frequently associated with various infections, including mycoses; however, the direct link between T1DM and fungal infections remains under-researched. This study utilizes a Mendelian randomization (MR) approach to investigate the potential causal relationship between T1DM and mycoses. Methods: Genetic variants associated with T1DM were sourced from the European Bioinformatics Institute database, while those related to fungal infections such as candidiasis, pneumocystosis, and aspergillosis were obtained from the Finngen database, focusing on European populations. The primary analysis was conducted using the inverse variance weighted (IVW) method, with additional insight from Mendelian randomization Egger regression (MR-Egger). Extensive sensitivity analyses assessed the robustness, diversity, and potential horizontal pleiotropy of our findings. Multivariable Mendelian randomization (MVMR) was employed to adjust for confounders, using both MVMR-IVW and MVMR-Egger to evaluate heterogeneity and pleiotropy. Results: Genetically, the odds of developing candidiasis increased by 5% in individuals with T1DM, as determined by the IVW method (OR = 1.05; 95% CI 1.02-1.07, p = 0.0001), with a Bonferroni-adjusted p-value of 0.008. Sensitivity analyses indicated no significant issues with heterogeneity or pleiotropy. Adjustments for confounders such as body mass index, glycated hemoglobin levels, and white blood cell counts further supported these findings (OR = 1.08; 95% CI:1.03-1.13, p = 0.0006). Additional adjustments for immune cell counts, including CD4 and CD8 T cells and natural killer cells, also demonstrated significant results (OR = 1.04; 95% CI: 1.02-1.06, p = 0.0002). No causal associations were found between T1DM and other fungal infections like aspergillosis or pneumocystosis. Conclusion: This MR study suggests a genetic predisposition for increased susceptibility to candidiasis in individuals with T1DM. However, no causal links were established between T1DM and other mycoses, including aspergillosis and pneumocystosis.

3.
Bioorg Med Chem Lett ; 110: 129865, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950758

RESUMO

Pyruvate kinase (PK) is an essential component of cellular metabolism, converting ADP and phosphoenolpyruvate (PEP) to pyruvate in the final step of glycolysis. Of the four unique isoforms of pyruvate kinase, R (PKR) is expressed exclusively in red blood cells and is a tetrameric enzyme that depends on fructose-1,6-bisphosphate (FBP) for activation. PKR deficiency leads to hemolysis of red blood cells resulting in anemia. Activation of PKR in both sickle cell disease and beta-thalassemia patients could lead to improved red blood cell fitness and survival. The discovery of a novel series of substituted urea PKR activators, via the serendipitous identification and diligent characterization of a minor impurity in an High Throughput Screening (HTS) hit will be discussed.

4.
Nat Commun ; 15(1): 5505, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951529

RESUMO

Atmospheric rivers (ARs) reaching high-latitudes in summer contribute to the majority of climatological poleward water vapor transport into the Arctic. This transport has exhibited long term changes over the past decades, which cannot be entirely explained by anthropogenic forcing according to ensemble model responses. Here, through observational analyses and model experiments in which winds are adjusted to match observations, we demonstrate that low-frequency, large-scale circulation changes in the Arctic play a decisive role in regulating AR activity and thus inducing the recent upsurge of this activity in the region. It is estimated that the trend in summertime AR activity may contribute to 36% of the increasing trend of atmospheric summer moisture over the entire Arctic since 1979 and account for over half of the humidity trends in certain areas experiencing significant recent warming, such as western Greenland, northern Europe, and eastern Siberia. This indicates that AR activity, mostly driven by strong synoptic weather systems often regarded as stochastic, may serve as a vital mechanism in regulating long term moisture variability in the Arctic.

5.
Nat Commun ; 15(1): 5580, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961062

RESUMO

DNA methylation plays an important role in various biological processes, including cell differentiation, ageing, and cancer development. The most important methylation in mammals is 5-methylcytosine mostly occurring in the context of CpG dinucleotides. Sequencing methods such as whole-genome bisulfite sequencing successfully detect 5-methylcytosine DNA modifications. However, they suffer from the serious drawbacks of short read lengths and might introduce an amplification bias. Here we present Rockfish, a deep learning algorithm that significantly improves read-level 5-methylcytosine detection by using Nanopore sequencing. Rockfish is compared with other methods based on Nanopore sequencing on R9.4.1 and R10.4.1 datasets. There is an increase in the single-base accuracy and the F1 measure of up to 5 percentage points on R.9.4.1 datasets, and up to 0.82 percentage points on R10.4.1 datasets. Moreover, Rockfish shows a high correlation with whole-genome bisulfite sequencing, requires lower read depth, and achieves higher confidence in biologically important regions such as CpG-rich promoters while being computationally efficient. Its superior performance in human and mouse samples highlights its versatility for studying 5-methylcytosine methylation across varied organisms and diseases. Finally, its adaptable architecture ensures compatibility with new versions of pores and chemistry as well as modification types.


Assuntos
5-Metilcitosina , Ilhas de CpG , Metilação de DNA , Sequenciamento por Nanoporos , 5-Metilcitosina/metabolismo , 5-Metilcitosina/química , Sequenciamento por Nanoporos/métodos , Animais , Camundongos , Humanos , Ilhas de CpG/genética , Aprendizado Profundo , Algoritmos , Análise de Sequência de DNA/métodos , Sequenciamento Completo do Genoma/métodos , Sulfitos/química
6.
Neurospine ; 21(2): 642-655, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38955534

RESUMO

OBJECTIVE: The therapeutic benefits of exosomes obtained from mesenchymal stem cells (MSCs) in acute spinal cord injury (SCI) have been demonstrated in recent years, but the precise mechanisms remain unknown. In this study, the efficacy and mechanisms of MSC-derived exosomes (MSC-Exo) in acute SCI were investigated. METHODS: By utilizing a BV2 ferroptosis cellular model and an SCI rat model, we investigated the effects of MSC-Exo on iron death related indicators and NF-E2 related factor 2 (Nrf2)/GTP cyclolase I (GCH1)/5,6,7,8-tetrahydrobiopterin (BH4) signaling axis, as well as their therapeutic effects on SCI rats. RESULTS: The results revealed that MSC-Exo effectively inhibited the production of ferrous iron, lipid peroxidation products malonaldehyde and reactive oxygen species, and ferroptosis-promoting factor prostaglandin-endoperoxide synthase 2. Concurrently, they upregulated ferroptosis suppressors FTH-1 (ferritin heavy chain 1), SLC7A11 (solute carrier family 7 member 11), FSP1 (ferroptosis suppressor protein 1), and GPX4 (glutathione peroxidase 4), contributing to enhanced neurological recovery in SCI rats. Further analysis showed the Nrf2/GTP/BH4 signaling pathway's critical role in suppressing ferroptosis. Additionally, MSC-Exo was found to inhibit lipopolysaccharide-induced ferroptosis in BV2 cells and SCI rats by activating the Nrf2/GCH1/BH4 axis. CONCLUSION: In summary, the study demonstrates that MSC-Exo mitigates microglial cell ferroptosis via the Nrf2/GCH1/BH4 axis, showing potential for preserving and restoring neurological function post-SCI.

7.
J Biochem Mol Toxicol ; 38(7): e23763, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38984790

RESUMO

The advanced non-small cell lung cancer (NSCLC) that harbors epidermal growth factor receptor (EGFR) mutations has put a selective pressure on the discovery and development of newer EGFR inhibitors. Therefore, the present study intends to explore the pharmacological effect of Araguspongine C (Aragus-C) as anticancer agent against lung cancer. The effect of Aragus-C was evaluated on the viability of the A549 and H1975 cells. Further biochemical assays were performed to elaborate the effect of Aragus-C, on the apoptosis, cell-cycle analysis, and mitochondrial membrane potential in A549 cells. Western blot analysis was also conducted to determine the expression of EGFR in A549 cells. Tumor xenograft mice model from A549 cells was established to further elaborate the pharmacological activity of Aragus-C. Results suggest that Aragus C showed significant inhibitory activity against A549 cells as compared to H1975 cells. It has been found that Aragus-C causes the induction of apoptosis and promotes cell-cycle arrest at the G2/M phase of A549 cells. It also showed a reduction in the overexpression of EGFR in A549 cells. In tumor xenograft mice model, it showed a significant reduction of tumor volume in a dose-dependent manner, with maximum inhibitory activity was reported by the 8 mg/kg treated group. It also showed significant anti-inflammatory and antioxidant activity by reducing the level of TNF-α, IL-1ß, IL-6, and MDA, with a simultaneous increase of superoxide dismutase and glutathione peroxidase. We have demonstrated the potent anti-lung cancer activity of Aragus-C, and it may be considered as a potential therapeutic choice for NSCLC treatment.


Assuntos
Apoptose , Receptores ErbB , Neoplasias Pulmonares , Estresse Oxidativo , Ensaios Antitumorais Modelo de Xenoenxerto , Humanos , Receptores ErbB/metabolismo , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Animais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Apoptose/efeitos dos fármacos , Células A549 , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Camundongos Nus , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Camundongos Endogâmicos BALB C , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral
8.
BMC Vet Res ; 20(1): 295, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971753

RESUMO

BACKGROUND: Fatty liver in dairy cows is a common metabolic disease defined by triglyceride (TG) buildup in the hepatocyte. Clinical diagnosis of fatty liver is usually done by liver biopsy, causing considerable economic losses in the dairy industry owing to the lack of more effective diagnostic methods. Therefore, this study aimed to investigate the potential utility of blood biomarkers for the diagnosis and early warning of fatty liver in dairy cows. RESULTS: A total of twenty-four lactating cows within 28 days after parturition were randomly selected as experimental animals and divided into healthy cows (liver biopsy tested, n = 12) and cows with fatty liver (liver biopsy tested, n = 12). Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the macroelements and microelements in the serum of two groups of cows. Compared to healthy cows (C), concentrations of calcium (Ca), potassium (K), magnesium (Mg), strontium (Sr), selenium (Se), manganese (Mn), boron (B) and molybdenum (Mo) were lower and copper (Cu) was higher in fatty liver cows (F). Meanwhile, the observed differences in macroelements and microelements were related to delivery time, with the greatest major disparity between C and F occurring 7 days after delivery. Multivariable analysis was used to test the correlation between nine serum macroelements, microelements and fatty liver. Based on variable importance projection and receiver operating characteristic (ROC) curve analysis, minerals Ca, Se, K, B and Mo were screened as the best diagnostic indicators of fatty liver in postpartum cows. CONCLUSIONS: Our data suggested that serum levels of Ca, K, Mg, Se, B, Mo, Mn, and Sr were lower in F than in C. The most suitable period for an early-warning identification of fatty liver in cows was 7 days after delivery, and Ca, Se, K, B and Mo were the best diagnostic indicators of fatty liver in postpartum cows.


Assuntos
Doenças dos Bovinos , Fígado Gorduroso , Período Periparto , Animais , Bovinos/sangue , Feminino , Doenças dos Bovinos/sangue , Doenças dos Bovinos/diagnóstico , Fígado Gorduroso/veterinária , Fígado Gorduroso/sangue , Fígado Gorduroso/diagnóstico , Período Periparto/sangue , Biomarcadores/sangue , Manganês/sangue , Oligoelementos/sangue , Molibdênio/sangue , Fígado/química , Potássio/sangue , Boro/sangue , Selênio/sangue , Cálcio/sangue , Magnésio/sangue , Gravidez
9.
World J Oncol ; 15(4): 579-591, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38993248

RESUMO

Background: Lymph node status is a prominent prognostic factor for intrahepatic cholangiocarcinoma (ICC). However, the prognostic value of performing lymph node dissection (LND) in patients with clinical node-negative ICC remains controversial. The aim of this study was to evaluate the clinical value of LND on long-term outcomes in this subgroup of patients. Methods: We retrospectively analyzed patients who underwent radical liver resection for clinically node-negative ICC from three tertiary hepatobiliary centers. The propensity score matching analysis at 1:1 ratio based on clinicopathological data was conducted between patients with and without LND. Recurrence-free survival (RFS) and overall survival (OS) were compared in the matched cohort. Results: Among 303 patients who underwent radical liver resection for ICC, 48 patients with clinically positive nodes were excluded, and a total of 159 clinically node-negative ICC patients were finally eligible for the study, with 102 in the LND group and 57 in the non-LND group. After propensity score matching, two well-balanced groups of 51 patients each were analyzed. No significant difference of median RFS (12.0 vs. 10.0 months, P = 0.37) and median OS (22.0 vs. 26.0 months, P = 0.47) was observed between the LND and non-LND group. Also, LND was not identified as one of the independent risks for survival. Among 51 patients who received LND, 11 patients were with positive lymph nodes (lymph node metastasis (LNM) (+)) and presented significantly worse outcomes than those with LND (-). On the other hand, postoperative adjuvant therapy was the independent risk factor for both RFS (hazard ratio (HR): 0.623, 95% confidence interval (CI): 0.393 - 0.987, P = 0.044) and OS (HR: 0.585, 95% CI: 0.359 - 0.952, P = 0.031). Furthermore, postoperative adjuvant therapy was associated with prolonged survivals of non-LND patients (P = 0.02 for RFS and P = 0.03 for OS). Conclusions: Based on the data, we found that LND did not significantly improve the prognosis of patients with clinically node-negative ICC. Postoperative adjuvant therapy was associated with prolonged survival of ICC patients, especially in non-LND individuals.

10.
Animal Model Exp Med ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38988280

RESUMO

BACKGROUND: Dengue fever, an acute insect-borne infectious disease caused by the dengue virus (DENV), poses a great challenge to global public health. Hepatic involvement is the most common complication of severe dengue and is closely related to the occurrence and development of disease. However, the features of adaptive immune responses associated with liver injury in severe dengue are not clear. METHODS: We used single-cell sequencing to examine the liver tissues of mild or severe dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection, and the immune interaction between macrophages and T cells. Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results. RESULTS: Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated. The reason may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type, and the macrophages then inhibit T cell immunity through the TGF-ß signaling pathway. In addition, the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice. CONCLUSIONS: In this study, single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice. Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.

11.
Sensors (Basel) ; 24(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39001164

RESUMO

Hyperspectral detection of the change rate of organic matter content in agricultural remote sensing requires a high signal-to-noise ratio (SNR). However, due to the large number and efficiency limitation of the components, it is difficult to improve the SNR. This study uses high-efficiency convex grating with a diffraction efficiency exceeding 50% across the 360-850 nm range, a back-illuminated Complementary Metal Oxide Semiconductor (CMOS) detector with a 95% efficiency in peak wavelength, and silver-coated mirrors to develop an imaging spectrometer for detecting soil organic matter (SOM). The designed system meets the spectral resolution of 10 nm in the 360-850 nm range and achieves a swath of 100 km and a spatial resolution of 100 m at an orbital height of 648.2 km. This study also uses the basic structure of Offner with fewer components in the design and sets the mirrors of the Offner structure to have the same sphere, which can achieve the rapid adjustment of the co-standard. This study performs a theoretical analysis of the developed Offner imaging spectrometer based on the classical Rowland circular structure, with a 21.8 mm slit length; simulates its capacity for suppressing the +2nd-order diffraction stray light with the filter; and analyzes the imaging quality after meeting the tolerance requirements, which is combined with the surface shape characteristics of the high-efficiency grating. After this test, the grating has a diffraction efficiency above 50%, and the silver-coated mirrors have a reflection value above 95% on average. Finally, the laboratory tests show that the SNR over the waveband exceeds 300 and reaches 800 at 550 nm, which is higher than some current instruments in orbit for soil observation. The proposed imaging spectrometer has a spectral resolution of 10 nm, and its modulation transfer function (MTF) is greater than 0.23 at the Nyquist frequency, making it suitable for remote sensing observation of SOM change rate. The manufacture of such a high-efficiency broadband grating and the development of the proposed instrument with high energy transmission efficiency can provide a feasible technical solution for observing faint targets with a high SNR.

12.
Angew Chem Int Ed Engl ; : e202410666, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39007416

RESUMO

Near-infrared region (NIR; 650-1700 nm) dyes offer many advantages over traditional dyes with absorption and emission in the visible region. However, developing new NIR dyes, especially organic dyes with long wavelengths, small molecular weight, and excellent stability and biocompatibility, is still quite challenging. Herein, we present a general method to enhance the absorption and emission wavelengths of traditional fluorophores by simply appending a charge separation structure, dihydropyridopyrazine. These novel NIR dyes not only exhibited greatly redshifted wavelengths compared to their parent dyes, but also displayed a small molecular weight increase together with retained stability and biocompatibility. Specifically, dye NIR-OX, a dihydropyridopyra-zine derivative of oxazine with a molecular mass of 386.2 Da, exhibited an absorption at 822 nm and an emission extending to 1200 nm, making it one of the smallest molecular-weight NIR-II emitting dyes. Thanks to its rapid metabolism and long wave-length, NIR-OX enabled high-contrast bioimaging and assessment of cholestatic liver injury in vivo and also facilitated the evalua-tion of the efficacy of liver protection medicines against cholestatic liver injury.

13.
J Steroid Biochem Mol Biol ; 243: 106577, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38971336

RESUMO

An UPLC-APCI-MS/MS method was developed for the simultaneous determination of cholesterol, 7-dehydrocholesterol (7DHC) and eight oxysterols including 27-hydroxycholesterol (27OHC), 7α-hydroxycholesterol (7αOHC), 7ß-hydroxycholesterol (7ßOHC), 24S-hydroxycholesterol (24SOHC), 25-hydroxycholesterol (25OHC), 7α,24S-dihydroxycholesterol (7α,24SdiOHC), 7α,25-dihydroxycholesterol (7α,25diOHC), and 7α,27-dihydroxycholesterol (7α,27diOHC). It has been used for quantitative analysis of cholesterol, 7DHC and eight oxysterols in hepatocellular carcinoma (HCC) cells, plasma and tumor tissue samples. And the above compounds were extracted from the biological matrix (plasma and tissue) using liquid-liquid extraction with hexane/isopropanol after saponification to cleave the steroids from their esterified forms without further derivatization. Then cholesterol, 7DHC and oxysterols were separated on a reversed phase column (Agilent Zorbax Eclipse plus, C18) within 8 min using a gradient elution with 0.1 % formic acid in H2O and methanol and detected by an APCI triple quadrupole mass spectrometer. The lower limit of quantification (LLOQ) of the cholesterol, 7DHC and oxysterols ranged from 3.9 ng/mL to 31.25 ng/mL, and the recoveries ranged from 83.0 % to 113.9 %. Cholesterol, 7DHC and several oxysterols including 27OHC, 7αOHC and 7ßOHC were successfully quantified in HCC cells, plasma, tissues and urine of HCC mice. Results showed that 27OHC was at high levels in three kind of HCC cells and tumor tissues as well as plasma samples from both HepG2 and Huh7 bearing mice model,and the high levels of 27OHC in tumors were associated with HCC development. Moreover, the levels of cholesterol in HCC cells and tumor issues varied in different HCC cells and mice model. Oxysterols profiling in biological samples might provide complementary information in cancer diagnosis.

14.
ISA Trans ; 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39033077

RESUMO

Data-driven based batch process monitoring is of critical importance in ensuring stable operating processes and consistent product quality. For long-duration batch processes, it is unrealistic to involve expensive data to train a statistical model for monitoring. To model the inherently batch-wise and variable-wise dynamics, nonlinearity, and time-varying characteristics, this paper proposes a local learning-based two-dimensional subspace identification (LL-2D-SID) scheme based on the similarity between the ongoing batch and the previous batches. The similarity is estimated by the extended extrapolative time-warping. Unlike the conventional statistical models using rich batch data, LL-2D-SID through online optimizing mechanism using limited batch data still has good prediction performance. The application of the sintering process in the polytetrafluoroethylene production has demonstrated that the LL-2D-SID based process monitoring scheme can not only accurately track temperature changes but also timely give fault alarms with a lower error alarm rate than the other SID-based process monitoring schemes.

15.
Medicine (Baltimore) ; 103(29): e38953, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39029064

RESUMO

To investigate the efficacy of Frankincense-Myrrh in lumbar Intervertebral degenerative diseases (LIDD). The active components of frankincense-myrrh was retrieved with a unique system pharmacology platform for Traditional Chinese Medicine Systems Pharmacology (TCMSP). The LIDD-related target genes were screened with DisGeNET and Genecards databases. Then, STRING & Cytoscape were used for analyzing the Protein-Protein Interaction network. DAVID was used for analyzing Gene Ontology (GO) & Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, molecules of AutoDockVina and Pymol were used for docking the molecules for verifying active ingredients and key targets' binding force. The 105 LIDD-related targets identified in Ruxiang (RX)-Moyao (MY) involve 53 active ingredients. In addition, topological analysis was conducted for identifying the 12 key targets. According to the analysis results of GO & KEGG, RX-MY is significant for treating LIDD through participating in many pathways and biological processes, such as signaling pathways of inflammatory response reactive process, MAP kinase activity, TNF, and MAPK, etc. According to the dock results, the active components oxo-tirucalic, acid, isofouquierone, (7S, 8R, 9S, 10R, 13S, 14S,17Z)-17-ethylidene-7-hydroxy-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15-decahydrocyclopenta [a] phenanthrene-3,16-dion in RX-MY binds actively. The basic pharmacological action and RX-MY-related mechanism in the treatment of LIDD was revealed in this study for the first time. It is predicted that the results may provide a treatment plan for RX-MY with replacement of NSAIDs and warrant investigation of new therapeutic alternatives for LIDD. However, these predictions should be validated by relevant pharmacological trials.


Assuntos
Degeneração do Disco Intervertebral , Simulação de Acoplamento Molecular , Farmacologia em Rede , Degeneração do Disco Intervertebral/tratamento farmacológico , Humanos , Farmacologia em Rede/métodos , Mapas de Interação de Proteínas/efeitos dos fármacos , Medicina Tradicional Chinesa/métodos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Vértebras Lombares
16.
Adv Mater ; : e2406246, 2024 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-39032067

RESUMO

Mixed tin-lead (Sn-Pb) perovskites have attracted the attention of the community due to their narrow bandgap, ideal for photovoltaic applications, especially tandem solar cells. However, the oxidation and rapid crystallization of Sn2+ and the interfacial traps hinder their development. Here, cross-linkable [6,6]-phenyl-C61-butyric styryl dendron ester (C-PCBSD) is introduced during the quenching step of perovskite thin film processing to suppress the generation of surface defects at the electron transport layer interface and improve the bulk crystallinity. The C-PCBSD has strong coordination ability with Sn2+ and Pb2+ perovskite precursors, which retards the crystallization process, suppresses the oxidation of Sn2+, and improves the perovskite bulk and surface crystallinity, yielding films with reduced nonradiative recombination and enhanced interface charge extraction. Besides, the C-PCBSD network deposited on the perovskite surface displays superior hydrophobicity and oxygen resistance. Consequently, the devices with C-PCBSD obtain PCEs of up to 23.4% and retained 97% of initial efficiency after 2000 h of storage in a N2 atmosphere.

17.
ACS Nano ; 18(28): 18693-18700, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38958405

RESUMO

Facing the challenge of information security in the current era of information technology, optical encryption based on metasurfaces presents a promising solution to this issue. However, most metasurface-based encryption techniques rely on limited decoding keys and struggle to achieve multidimensional complex encryption. It hinders the progress of optical storage capacity and puts encryption security at a disclosing risk. Here, we propose and experimentally demonstrate a multidimensional encryption system based on chip-integrated metasurfaces that successfully incorporates the simultaneous manipulation of three-dimensional optical parameters, including wavelength, direction, and polarization. Hence, up to eight-channel augmented reality (AR) holograms are concealed by near- and far-field fused encryption, which can only be extracted by correctly providing the three-dimensional decoding keys and then vividly exhibit to the authorizer with low crosstalk, high definition, and no zero-order speckle noise. We envision that the miniature chip-integrated metasurface strategy for multidimensional encryption functionalities promises a feasible route toward the encryption capacity and information security enhancement of the anticounterfeiting performance and optically cryptographic storage.

18.
Langmuir ; 40(26): 13458-13466, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38887034

RESUMO

Single-atom catalysts (SACs) are attractive in one-carbon (C1) chemistry because of their high atom efficiency. However, it is a great challenge for understanding the dynamic roles of SACs under operating conditions. Here, isolated Pt atoms trapped on defective CeO2 surface are investigated by experiments, especially operando techniques, which offers basic understanding of the nature and dynamic evolution of the Pt-CeO2 interface in dry reforming of methane (DRM). The Pt-Olattice configuration is highly active for CH4 dissociation at the expense of the Olattice atoms, which in turn promotes the H-assisted dissociation of CO2. The transformation of Pt atoms between positive and metallic states is driven by the DRM reaction, which is essential for rendering highly efficient catalysis. The dynamic evolution of Pt atoms favors to eliminate the reactive intermediates, such as carbonates and formates. The dynamic nature of the Pt-CeO2 interface in the DRM reaction shows a similar picture to the Yin and Yang transformation in ancient Chinese Tai Ji wisdom.

19.
Int J Mol Sci ; 25(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891866

RESUMO

Vibrio fluvialis is an emerging foodborne pathogenic bacterium that can cause severe cholera-like diarrhea and various extraintestinal infections, posing challenges to public health and food safety worldwide. The arginine deiminase (ADI) pathway plays an important role in bacterial environmental adaptation and pathogenicity. However, the biological functions and regulatory mechanisms of the pathway in V. fluvialis remain unclear. In this study, we demonstrate that L-arginine upregulates the expression of the ADI gene cluster and promotes the growth of V. fluvialis. The ADI gene cluster, which we proved to be comprised of two operons, arcD and arcACB, significantly enhances the survival of V. fluvialis in acidic environments both in vitro (in culture medium and in macrophage) and in vivo (in mice). The mRNA level and reporter gene fusion analyses revealed that ArgR, a transcriptional factor, is necessary for the activation of both arcD and arcACB transcriptions. Bioinformatic analysis predicted the existence of multiple potential ArgR binding sites at the arcD and arcACB promoter regions that were further confirmed by electrophoretic mobility shift assay, DNase I footprinting, or point mutation analyses. Together, our study provides insights into the important role of the ArgR-ADI pathway in the survival of V. fluvialis under acidic conditions and the detailed molecular mechanism. These findings will deepen our understanding of how environmental changes and gene expression interact to facilitate bacterial adaptations and virulence.


Assuntos
Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Hidrolases , Animais , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Camundongos , Hidrolases/metabolismo , Hidrolases/genética , Regiões Promotoras Genéticas , Óperon/genética , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Vibrio/genética , Vibrio/metabolismo , Vibrio/patogenicidade , Arginina/metabolismo , Família Multigênica , Virulência/genética , Viabilidade Microbiana
20.
NPJ Vaccines ; 9(1): 119, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926425

RESUMO

Persistent infection with high-risk human papillomavirus (HPV) is widely recognized as the primary cause of cervical and other malignant cancers. There are six licensed prophylactic vaccines available against HPV, but none of them shows any significant therapeutic effect on pre-existing infections or lesions. Thus, a prophylactic vaccine also endowed with therapeutic activity would afford protection regardless of the vaccine recipients HPV-infection status. Here, we describe the refinement and further potentiation of a dual-purpose HPV nanoparticle vaccine (hereafter referred to as cPANHPVAX) relying on eight different HPV L2 peptide epitopes and on the E7 oncoantigens from HPV16 and 18. cPANHPVAX not only induces anti-HPV16 E7 cytotoxic T-cell responses in C57BL/6 mice, but also anti-HPV18 E7 T-cell responses in transgenic mice with the A2.DR1 haplotype. These cytotoxic responses add up to a potent, broad-coverage humoral (HPV-neutralizing) response. cPANHPVAX safety was further improved by deletion of the pRb-binding domains of E7. Our dual-purpose vaccine holds great potential for clinical translation as an immune-treatment capable of targeting active infections as well as established HPV-related malignancies, thus benefiting both uninfected and infected individuals.

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