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1.
Oncologist ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38907674

RESUMO

BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

2.
Biochem Biophys Res Commun ; 696: 149472, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38241809

RESUMO

Lysosomal dysfunction and impaired autophagic flux are involved in the pathogenesis of lipotoxicity in the kidney. Here, we investigated the role of transcription factor EB (TFEB), a master regulator of autophagy-lysosomal pathway, in palmitic acid induced renal tubular epithelial cells injury. We examined lipid accumulation, autophagic flux, expression of Ps211-TFEB, and nuclear translocation of TFEB in HK-2 cells overloaded with palmitic acid (PA). By utilizing immunohistochemistry, we detected TFEB expression in renal biopsy tissues from patients with diabetic nephropathy and normal renal tissue adjacent to surgically removed renal carcinoma (controls), as well as kidney tissues from rat fed with high-fat diet (HFD) and low-fat diet (LFD). We found significant lipid accumulation, increased apoptosis, accompanied with elevated Ps211-TFEB, decreased nuclear TFEB, reduced lysosome biogenesis and insufficient autophagy in HK-2 cells treated with PA. Kidney tissues from patients with diabetic nephropathy had lower nuclear and total levels of TFEB than that in control kidney tissues. Level of renal nuclear TFEB in HFD rats was also lower than that in LFD rats. Exogenous overexpression of TFEB increased the nuclear TFEB level in HK-2 cells treated with PA, promoted lysosomal biogenesis, improved autophagic flux, reduced lipid accumulation and apoptosis. Our results collectively indicate that PA is a strong inducer for TFEB phosphorylation modification at ser211 accompanied with lower nuclear translocation of TFEB. Impairment of TFEB-mediated lysosomal biogenesis and function by palmitic acid may lead to insufficient autophagy and promote HK-2 cells injury.


Assuntos
Nefropatias Diabéticas , Ácido Palmítico , Ratos , Humanos , Animais , Ácido Palmítico/farmacologia , Ácido Palmítico/metabolismo , Nefropatias Diabéticas/metabolismo , Autofagia , Lisossomos/metabolismo , Células Epiteliais/metabolismo , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo
3.
BMC Cancer ; 24(1): 902, 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39061024

RESUMO

BACKGROUND: TBK1 positively regulates the growth factor-mediated mTOR signaling pathway by phosphorylating mTOR. However, it remains unclear how the TBK1-mTOR signaling pathway is regulated. Considering that STING not only interacts with TBK1 but also with MARCH1, we speculated that MARCH1 might regulate the mTOR signaling pathway by targeting TBK1. The aim of this study was to determine whether MARCH1 regulates the mTOR signaling pathway by targeting TBK1. METHODS: The co-immunoprecipitation (Co-IP) assay was used to verify the interaction between MARCH1 with STING or TBK1. The ubiquitination of STING or TBK1 was analyzed using denatured co-immunoprecipitation. The level of proteins detected in the co-immunoprecipitation or denatured co-immunoprecipitation samples were determined by Western blotting. Stable knocked-down cells were constructed by infecting lentivirus bearing the related shRNA sequences. Scratch wound healing and clonogenic cell survival assays were used to detect the migration and proliferation of breast cancer cells. RESULTS: We showed that MARCH1 played an important role in growth factor-induced the TBK1- mTOR signaling pathway. MARCH1 overexpression attenuated the growth factor-induced activation of mTOR signaling pathway, whereas its deficiency resulted in the opposite effect. Mechanistically, MARCH1 interacted with and promoted the K63-linked ubiquitination of TBK1. This ubiquitination of TBK1 then attenuated its interaction with mTOR, thereby inhibiting the growth factor-induced mTOR signaling pathway. Importantly, faster proliferation induced by MARCH1 deficiency was weakened by mTOR, STING, or TBK1 inhibition. CONCLUSION: MARCH1 suppressed growth factors mediated the mTOR signaling pathway by targeting the STING-TBK1-mTOR axis.


Assuntos
Proliferação de Células , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Serina-Treonina Quinases TOR , Ubiquitina-Proteína Ligases , Ubiquitinação , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Humanos , Serina-Treonina Quinases TOR/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Linhagem Celular Tumoral , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Feminino , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Movimento Celular
4.
Langmuir ; 40(1): 818-826, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38146702

RESUMO

It is significant to understand the adsorption mechanisms of shale gas (CH4) and CO2 in shale formations to enhance CH4 recovery rates and enable geological CO2 storage. This study provides a comprehensive investigation into the adsorption behaviors of CO2 and CH4 within dry and hydrous calcite nanopores, utilizing a combination of grand canonical Monte Carlo simulations, molecular dynamics simulations, and density functional theory calculations. In dry calcite slits, the calculated results for the adsorption capacity, density profile, and isosteric heat of CO2 and CH4 reveal that CO2 possesses a stronger adsorption affinity, making it preferentially adsorb on the pore surface compared to CH4. In hydrous calcite slits, calculating the adsorption capacity and density profile of CO2 and CH4, the results show that the gas adsorption sites become progressively occupied by H2O molecules, leading to a substantial decrease in the adsorption capacity of CO2 and CH4. Furthermore, by analysis of the adsorption energy and electronic structure, the reason for the reduction of gas adsorption capacity caused by H2O is further revealed. This work has a deep understanding of the adsorption mechanisms of shale gas and CO2 in calcite and can offer valuable theoretical insights for the development of a CO2-enhanced shale gas recovery technology.

5.
Phys Chem Chem Phys ; 26(21): 15181-15191, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38752328

RESUMO

In this paper, we propose a new two-step strategy for computing ro-vibrational energy levels and wavefunctions of a triatomic molecule and apply it to CO2. A two-step method [J. Tennyson and B. T. Sutcliffe, Mol. Phys., 1986, 58, 1067] uses a basis whose functions are products of K-dependent "vibrational" functions and symmetric top functions. K is the quantum number for the molecule-fixed z component of the angular momentum. For a linear molecule, a two-step method is efficient because the Hamiltonian used to compute the basis functions includes the largest coupling term. The most important distinguishing feature of the two-step method we propose is that it uses an associated Legendre basis and quadrature rather than a K-dependent discrete variable representation. This reduces the cost of the calculation and simplifies the method. We have computed ro-vibrational energy levels with J up to 100 for CO2, on an accurate available potential energy surface which is known as the AMES-2 PES and present a subset of those levels. We have converged most levels up to 20 000 cm-1 to 0.0001 cm-1.

6.
J Nat Prod ; 87(4): 966-975, 2024 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-38441877

RESUMO

Ten new (1-10) and nine known (11-19) austocystins, along with four known anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1″-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 µM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 µM, respectively.


Assuntos
Aspergillus , Imunossupressores , Aspergillus/química , Humanos , Imunossupressores/farmacologia , Imunossupressores/química , Imunossupressores/isolamento & purificação , Estrutura Molecular , Cristalografia por Raios X , Interleucina-6/metabolismo , Antraquinonas/farmacologia , Antraquinonas/química , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Linfócitos T/efeitos dos fármacos , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Proliferação de Células/efeitos dos fármacos
7.
Acta Pharmacol Sin ; 45(5): 1060-1076, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38228910

RESUMO

Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro. Through high-throughput sequencing, we identified the SHH-initiated Hedgehog signaling pathway playing an important role in this process. We demonstrated that triptolide directly bound to HNF1A, one of the transcription factors of SHH, and inhibited HNF1A/SHH expression, ensuing in attenuation of Hedgehog signaling. In NSCLC tumor tissue microarrays and cancer network databases, we found a positive correlation between HNF1A and SHH expression. Our results illuminate a novel molecular mechanism through which triptolide targets and inhibits HNF1A, thereby impeding the activation of the Hedgehog signaling pathway and reducing the expression of ABCB1. This study suggests the potential clinical application of triptolide and provides promising prospects in targeting the HNF1A/SHH pathway as a therapeutic strategy for NSCLC patients with paclitaxel resistance. Schematic diagram showing that triptolide overcomes paclitaxel resistance by mediating inhibition of the HNF1A/SHH/ABCB1 axis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Diterpenos , Resistencia a Medicamentos Antineoplásicos , Compostos de Epóxi , Proteínas Hedgehog , Fator 1-alfa Nuclear de Hepatócito , Neoplasias Pulmonares , Paclitaxel , Fenantrenos , Compostos de Epóxi/farmacologia , Compostos de Epóxi/uso terapêutico , Humanos , Fenantrenos/farmacologia , Fenantrenos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Hedgehog/metabolismo , Fator 1-alfa Nuclear de Hepatócito/metabolismo , Fator 1-alfa Nuclear de Hepatócito/genética , Animais , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Camundongos Nus , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Camundongos , Camundongos Endogâmicos BALB C , Células A549
8.
Acta Pharmacol Sin ; 45(9): 1793-1808, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38740904

RESUMO

The circadian clock is the inner rhythm of life activities and is controlled by a self-sustained and endogenous molecular clock, which maintains a ~ 24 h internal oscillation. As the core element of the circadian clock, BMAL1 is susceptible to degradation through the ubiquitin-proteasome system (UPS). Nevertheless, scant information is available regarding the UPS enzymes that intricately modulate both the stability and transcriptional activity of BMAL1, affecting the cellular circadian rhythm. In this work, we identify and validate UBR5 as a new E3 ubiquitin ligase that interacts with BMAL1 by using affinity purification, mass spectrometry, and biochemical experiments. UBR5 overexpression induced BMAL1 ubiquitination, leading to diminished stability and reduced protein level of BMAL1, thereby attenuating its transcriptional activity. Consistent with this, UBR5 knockdown increases the BMAL1 protein. Domain mapping discloses that the C-terminus of BMAL1 interacts with the N-terminal domains of UBR5. Similarly, cell-line-based experiments discover that HYD, the UBR5 homolog in Drosophila, could interact with and downregulate CYCLE, the BMAL1 homolog in Drosophila. PER2-luciferase bioluminescence real-time reporting assay in a mammalian cell line and behavioral experiments in Drosophila reveal that UBR5 or hyd knockdown significantly reduces the period of the circadian clock. Therefore, our work discovers a new ubiquitin ligase UBR5 that regulates BMAL1 stability and circadian rhythm and elucidates the underlying molecular mechanism. This work provides an additional layer of complexity to the regulatory network of the circadian clock at the post-translational modification level, offering potential insights into the modulation of the dysregulated circadian rhythm.


Assuntos
Fatores de Transcrição ARNTL , Ritmo Circadiano , Ubiquitina-Proteína Ligases , Ubiquitinação , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Fatores de Transcrição ARNTL/metabolismo , Fatores de Transcrição ARNTL/genética , Animais , Humanos , Ritmo Circadiano/fisiologia , Células HEK293 , Proteólise , Relógios Circadianos/fisiologia , Proteínas Circadianas Period/metabolismo , Proteínas Circadianas Period/genética
9.
BMC Med Imaging ; 24(1): 117, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773416

RESUMO

BACKGROUND: Coronary inflammation induces changes in pericoronary adipose tissue (PCAT) can be detected by coronary computed tomography angiography (CCTA). Our aim was to investigate whether different PCAT radiomics model based on CCTA could improve the prediction of major adverse cardiovascular events (MACE) within 3 years. METHODS: This retrospective study included 141 consecutive patients with MACE and matched to patients with non-MACE (n = 141). Patients were randomly assigned into training and test datasets at a ratio of 8:2. After the robust radiomics features were selected by using the Spearman correlation analysis and the least absolute shrinkage and selection operator, radiomics models were built based on different machine learning algorithms. The clinical model was then calculated according to independent clinical risk factors. Finally, an overall model was established using the radiomics features and the clinical factors. Performance of the models was evaluated for discrimination degree, calibration degree, and clinical usefulness. RESULTS: The diagnostic performance of the PCAT model was superior to that of the RCA-model, LAD-model, and LCX-model alone, with AUCs of 0.723, 0.675, 0.664, and 0.623, respectively. The overall model showed superior diagnostic performance than that of the PCAT-model and Cli-model, with AUCs of 0.797, 0.723, and 0.706, respectively. Calibration curve showed good fitness of the overall model, and decision curve analyze demonstrated that the model provides greater clinical benefit. CONCLUSION: The CCTA-based PCAT radiomics features of three major coronary arteries have the potential to be used as a predictor for MACE. The overall model incorporating the radiomics features and clinical factors offered significantly higher discrimination ability for MACE than using radiomics or clinical factors alone.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Tecido Adiposo Epicárdico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Tecido Adiposo Epicárdico/diagnóstico por imagem , Aprendizado de Máquina , Radiômica , Estudos Retrospectivos
10.
Eur Spine J ; 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39095489

RESUMO

OBJECTIVE: This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed. METHODS: We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed. RESULTS: A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4%, 95.7%, and 93.8%, respectively); the area under the receiver operating characteristic curve (AUC) was 0.981, similar to the results of internal validation using bootstrap resampling (1000 replicates) and external validation set, indicating good clinical predictive ability. CONCLUSIONS: This study develop a good diagnostic model based on both CT and MRI, as well as laboratory findings, which may help clinicians distinguish between TS and PS.

11.
Pestic Biochem Physiol ; 202: 105956, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879338

RESUMO

Pepper southern blight, caused by Sclerotium rolfsii, is a devastating soil-borne disease resulting in significant loss to pepper, Capsicum annuum L. production. Here, we isolated an antagonistic bacterial strain XQ-29 with antifungal activity against S. rolfsii from rhizospheric soil of pepper. Combining the morphological and biochemical characteristics with the 16S rDNA sequencing, XQ-29 was identified as Streptomyces griseoaurantiacus. It exhibited an inhibition of 96.83% against S. rolfsii and displayed significant inhibitory effects on Botrytis cinerea, Phytophthora capsica and Rhizoctonia solani. Furthermore, XQ-29 significantly reduced the pepper southern blight by 100% and 70.42% during seedling and growth stages, respectively. The antifungal mechanism involved altering the mycelial morphology, disrupting cell wall and membrane integrity, accompanied by accumulation of reactive oxygen species and lipid peroxidation in S. rolfsii mycelia. Furthermore, XQ-29 promoted growth and stimulated resistance of pepper plants by increasing defense-related enzyme activities and upregulating defense-related genes. Correspondingly, XQ-29 harbors numerous functional biosynthesis gene clusters in its genome, including those for siderophores and melanin production. The metabolic constituents present in the ethyl acetate extracts, which exhibited an EC50 value of 85.48 ± 1.62 µg/mL, were identified using LC-MS. Overall, XQ-29 demonstrates significant potential as a biocontrol agent against southern blight disease.


Assuntos
Botrytis , Capsicum , Doenças das Plantas , Rhizoctonia , Streptomyces , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Capsicum/microbiologia , Streptomyces/genética , Streptomyces/fisiologia , Botrytis/efeitos dos fármacos , Botrytis/fisiologia , Rhizoctonia/fisiologia , Rhizoctonia/efeitos dos fármacos , Basidiomycota/fisiologia , Phytophthora/fisiologia , Phytophthora/efeitos dos fármacos , Agentes de Controle Biológico/farmacologia , Antifúngicos/farmacologia
12.
Sheng Li Xue Bao ; 76(1): 59-76, 2024 Feb 25.
Artigo em Zh | MEDLINE | ID: mdl-38444132

RESUMO

Intracerebral hemorrhage (ICH) is the most common subtype of stroke with high disability and high mortality rates. Due to the hypertension with arteriosclerosis, hemopathy and cerebrovascular amyloidosis, the influx of blood from ruptured vessels into the brain destroys the cerebral parenchyma and results in dysfunction of central nervous system because of hematoma compression and a series of toxic metabolites. The cerebral parenchyma consists of gray and white matter. The white matter consists of myelinated axons and oligodendrocytes, whereas the gray matter consists of neuronal cell bodies and dendrites. Currently, most of studies have explored the mechanisms of gray matter injury. But researches of white matter injury (WMI) are still in their infancy, which may be partially responsible for the failure of treatments with neuroprotectants targeting degenerating neuronal cells. In recent years, researchers have progressively identified pathophysiological mechanisms of WMI after ICH including mass effect, neuroinflammation and oxidative stress, but information on the molecular mechanisms of WMI and its effective treatment remains limited. In this paper, we will describe the structure and function of white matter, summarize pathology of WMI and focus on the research advances in the molecular mechanisms and therapeutic strategies of WMI after ICH.


Assuntos
Acidente Vascular Cerebral , Substância Branca , Humanos , Hemorragia Cerebral/terapia , Encéfalo , Córtex Cerebral
13.
Entropy (Basel) ; 26(1)2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38248178

RESUMO

In this paper, a unified gas kinetic particle (UGKP) method is developed for radiative transfer in both absorbing and anisotropic scattering media. This numerical method is constructed based on our theoretical work on the model reduction for an anisotropic scattering system. The macroscopic solver of this method directly solves the macroscopic anisotropic diffusion equations, eliminating the need to solve higher-order moment equations. The reconstruction of macroscopic scattering source in the microscopic solver, based on the multiscale equivalent phase function we proposed in this work, has also been simplified as one single scattering process, significantly reducing the computational costs. The proposed method has also the property of asymptotic preserving. In the optically thick regime, the proposed method solves the diffusion limit equations for an anisotropic system. In the optically thin regime, the kinetic processes of photon transport are simulated. The consistency and efficiency of the proposed method have been validated by numerical tests in a wide range of flow regimes. The novel equivalent scattering source reconstruction can be used for various transport processes, and the proposed numerical scheme is widely applicable in high-energy density engineering applications.

14.
Zhongguo Zhong Yao Za Zhi ; 49(11): 3113-3124, 2024 Jun.
Artigo em Zh | MEDLINE | ID: mdl-39041170

RESUMO

This study aims to analyze the current situation of outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) treatment for Alzheimer's disease(AD), so as to provide a reference for establishing a core indicator set in this field. The researchers systematically searched CNKI, Wanfang, VIP, Sino Med, EMbase, PubMed, Medline, and Cochrane Library. Independent screening of literature and extraction of information was conducted according to the inclusion and exclusion criteria. In addition, the Ro B 2. 0 tool was used for bias risk assessment. A total of 78 RCTs were included, involving 6 379 patients,with 122 kinds of outcome indicators. According to functional attributes, the outcome indicators could be categorized into seven groups:TCM diseases(3 kinds, 13 times), symptoms and signs(26 kinds, 196 times), physical and chemical tests(68 kinds, 149 times),qua-lity of life(1 kind, 2 times), long-term prognosis(2 kinds, 2 times), economic evaluation(0 kind), safety events(21 kinds,194 times), and other indicators(1 kind, 1 time). The results show that the literature evaluation of RCTs of TCM treatment for AD is generally risky, and there are some problems in the selection of outcome indicators, such as lack of TCM characteristics, insignificant distinction between primary and secondary outcome indicators, lack of long-term prognosis and economic evaluation indicators, and non-standard safety event reports. It is suggested that future researchers should establish a core indicator set for AD that highlights the characteristics of TCM and then work to improve the quality of clinical trials.


Assuntos
Doença de Alzheimer , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como Assunto , Doença de Alzheimer/tratamento farmacológico , Humanos , Medicamentos de Ervas Chinesas/uso terapêutico , Resultado do Tratamento , Idoso
15.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2722-2727, 2024 May.
Artigo em Zh | MEDLINE | ID: mdl-38812172

RESUMO

This study investigated the chemical and biological activity of the secondary metabolites from an endophytic fungus Fusa-rium solani MBM-5 of Datura arborea. A total of six alkenoic acid compounds, including a new compound and five known ones, were isolated from the ethyl acetate extract of F. solani MBM-5 by using the chromatographic methods(open ODS column chromatography, silica gel column chromatography, Sephadex LH-20, and semi-preparative HPLC). The structures of the compounds were identified by using their physical and chemical data, spectroscopic methods(UV, IR, NMR, and HR-ESI-MS), and Mosher's reaction, which were fusaridioic acid E(1), fusaridioic acid C(2), fusaridioic acid A(3), L660282(4), hymeglusin(5), and hymeglnone(6). Compound 1 is new. MTT assay and Griss method were used to evaluate the growth inhibition of all the compounds against two tumor cells, as well as their influence and anti-inflammatory action on the release of NO from LPS-induced RAW264.7 cells. The results showed that compound 5 had strong growth inhibition activity against A549 and HepG2 cell lines, with IC_(50) values of 4.70 and 13.57 µmol·L~(-1), respectively. Compounds 1 and 6 significantly inhibited the release of NO from LPS-induced RAW264.7 cells, with IC_(50) values of 77.00 and 70.33 µmol·L~(-1), respectively.


Assuntos
Endófitos , Fusarium , Metabolismo Secundário , Fusarium/efeitos dos fármacos , Fusarium/química , Camundongos , Humanos , Animais , Endófitos/química , Linhagem Celular Tumoral , Células RAW 264.7 , Estrutura Molecular , Óxido Nítrico/metabolismo , Proliferação de Células/efeitos dos fármacos
16.
Zhongguo Zhong Yao Za Zhi ; 49(6): 1632-1640, 2024 Mar.
Artigo em Zh | MEDLINE | ID: mdl-38621948

RESUMO

This study aims to explore the effects of tetramethylpyrazine(TMP) on pharmacokinetics in plasma and brain dialysate and neuropathic pain in the rat model of partial sciatic nerve injury(SNI), and to investigate the correlation between the analgesic effect of TMP and its concentrations in the plasma and brain dialysate. Male SD rats were randomized into Sham, SNI, and SNI+TMP groups. Mechanical stimulation with von frey filaments and cold spray method were employed to evaluate the mechanical sensitivity and cold sensitivity of rats. Another two groups, Sham+TMP and SNI+TMP, were used to intubate the common jugular vein and implant microdialysis probes into the anterior cingulate gyrus(ACC), respectively.After intraperitoneal injection of TMP at a dose of 80 mg·kg~(-1), automatic blood collection and intracerebral microdialysis(perfusion rate of 1 µL·min~(-1)) systems were used to collect the blood and brain dialysate for 24 h. HSS T3 C_(18) reversed-phase chromatographic column(2.1 mm×50 mm, 2.5 µm) was used for liquid chromatographic separation. Gradient elution was carried out with the mobile phase of methanol-water(containing 0.005% formic acid) at a flow rate of 0.25 mL·min~(-1). Electrospray ion source was used for mass spectrometry, and the scanning mode was multi-reaction monitoring under the positive ion mode. The ion pairs for quantitative analysis were TMP m/z 137/122 and aspirin m/z 179/137, respectively. DAS 2.11 was used to calculate the pharmacokinetic parameters. The optimal time of TMP to exert the analgesia effect and inhibit cold pain sensitivity was 60 min after treatment. The TMP in the plasma and brain dialysate of SNI rats showed the T_(max) of 15 min and 30 min, the C_(max) of(2 866.43±135.39) and(1 462.14±197.38) µg·L~(-1), the AUC_(0-t) of(241 463.30±28 070.31) and(213 115.62±32 570.07) µg·min·L~(-1), the MRT_(0-t) of(353.13±47.73) and(172.16±12.72) min, and the CL_Z of 0.73 and 0.36 L·min·kg~(-1), respectively. The analgesic effect of TMP had a significant correlation with the blood drug concentration in the ACC, which indicated that this method was suitable for the detection of TMP in rat plasma and brain dialysate. The method is accurate, reliable, and sensitive and can realize the important value of the application of correlation analysis theory of "automatic blood collection-microdialysis/PK-PD" in the research on neuropathic pain.


Assuntos
Encéfalo , Neuralgia , Pirazinas , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Neuralgia/tratamento farmacológico , Nervo Isquiático , Analgésicos
19.
Sci Rep ; 14(1): 9594, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38671032

RESUMO

Knowledge graphs are now widely used in various domains, including Question-and-answer systems, intelligent search and recommendation systems, and intelligent decision-making systems. However, knowledge graphs inevitably contain inaccurate and incomplete knowledge during the creation process, which leads to a reduction in the usefulness of knowledge graphs. Therefore, to assess the usefulness of knowledge graphs based on specific application requirements, quality assessment is particularly important. Among them, accuracy assessment, as a necessary dimension, reflects the degree of correctness of the triples. However, in the actual assessment process, the existing assessment methods do not consider the user's needs and do not implement the concept of "Fitness for Use". Meanwhile, it takes a lot of labor cost to evaluate the accuracy of large-scale knowledge graphs. Therefore, to ensure the accuracy of the assessment in a cost-saving way while meeting the needs of users, we propose and implement a novel accuracy assessment method that focuses on the requirements of users by designing an effective sampling method to obtain accurate assessment results that are more practical and instructive for users. Finally, the performance of our proposed method is evaluated by comparing it with the real accuracy rate, and the experimental results show that the accuracy rate obtained by the proposed method is very close to the real accuracy rate, and the sample size is minimized.

20.
Transl Cancer Res ; 13(7): 3556-3574, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39145082

RESUMO

Background: Osteosarcoma (OS) poses significant challenges in treatment and lacks reliable prognostic markers. Epigenetic alterations play a crucial role in disease progression. This study aimed to develop an accurate prognostic signature for OS using epigenetic modification genes (EMGs). Methods: The Therapeutically Applicable Research to Generate Effective Treatments (TARGET)-OS cohort was analyzed. Univariate Cox analysis identified survival-associated EMGs. Based on least absolute shrinkage and selection operator (LASSO) regression and multivariate analysis, a 6-gene prognostic signature termed the epigenetic modification-related prognostic signature (EMRPS) was derived in the testing cohort. Kaplan-Meier and receiver operating characteristic (ROC) curve analysis confirmed predictive accuracy through internal and external validation (GEO accession GSE21257). A prognostic nomogram incorporating EMRPS and clinical features was constructed. Transcriptomic analysis including differential gene expression, Gene Ontology (GO), gene set enrichment analysis (GSEA), and immune infiltration analysis was conducted to explore mechanisms linking EMRPS to OS prognosis. Additionally, EMRPS impact on drug sensitivity was predicted. Results: A 6-gene EMRPS comprising DDX24, DNAJC1, HDAC4, SIRT7, SP140 and UHRF2 was successfully developed. The high-risk group showed significantly shorter survival, consistently observed in both internal and external validation. EMRPS demonstrated high predictive efficacy for 1-, 3-, and 5-year overall survival, with area under curve (AUC) >0.85 in training and ~0.7 in testing. The nomogram integrating age, gender, metastasis status, and EMRPS exhibited high predictive performance based on concordance index analysis. Mechanistic analysis indicated the low-risk group had increased immune infiltration and activity with higher immune checkpoint expression, reflecting an immune-activated tumor microenvironment (TME) suitable for immunotherapy. Drug sensitivity analysis revealed the low-risk group had increased sensitivity to cisplatin, a first-line OS chemotherapy. Conclusions: Our study successfully established an efficient EMRPS and nomogram, highlighting their potential as novel prognostic markers and indicators for selecting appropriate immunotherapy and chemotherapy candidates in OS treatment.

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