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1.
Sci Adv ; 10(40): eadq6727, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39365856

RESUMO

Pt-based nanoparticles (NPs) have been widely used in catalysis. However, this suffers from aggregation and/or sintering at working conditions. We demonstrate a robust strategy for stabilizing PtCo NPs under high temperature with strong interaction between M-N-C and PtCo NPs with Pt-M-N coordination, namely, "atom glue." Such atom glue for stabilizing Pt-based NPs can be extended to Zn, Mn, Fe, Ni, Co, and Cu, being a versatile strategy for stabilizing PtCo NPs, which substantially promotes the performance toward oxygen reduction reaction (ORR) and fuel cell. Impressively, the mass activity (MA) reaches 2.99 A mgPt-1 for ORR over g-Zn-N-C/PtCo, and 79.3% of the initial MA is maintained after 90K cycles in fuel cell. This work provides a versatile strategy for stabilizing Pt-based NPs via atom glue, which is likely to spark widespread interest across various fields.

2.
Chin Med ; 19(1): 134, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39367502

RESUMO

Chronic gastritis (CG) is a common inflammatory disease of chronic inflammatory lesion of gastric mucosa and in the diagnosis of gastritis in traditional Chinese medicine (TCM), CG can be classified into Cold ZHENG (syndrome in TCM) and Hot ZHENG. However, the molecular features of Cold/Hot ZHENG in CG and the mechanism of Cold/Hot herbs in formulae for CG remained unclear. In this study, we collected a transcriptomics data including 35 patients of Cold/Hot ZHENG CG and 3 scRNA-seq CG samples. And 25 formulae for CG and 89 herbs recorded in these formulae were also collected. We conduct a comprehensive analysis based on the combination of transcriptomics datasets and machine learning algorithms, to discover biomarkers for Cold/Hot ZHENG CG. Then the target profiles of the collected formulae and Cold/Hot herbs were predicted to uncover the features and biomarkers of them against Cold/Hot ZHENG CG. These biomarkers suggest that Hot ZHENG CG might be characterized by over-inflammation and exuberant metabolism, and Cold ZHENG CG showed a trend of suppression in immune regulation and energy metabolism. Biomarkers and specific pathways of Hot herbs tend to regulate immune responses and energy metabolism, while those of Cold herbs are more likely to participate in anti-inflammatory effects. Finally, the findings were verified based on public transcriptomics datasets, as well as transcriptomics and ELISA detection, taking Jin Hong tablets as a case study. Biomarkers like leptin and IL-6 together with proportions of immune cells showed significant changes after the intervention. These findings might reflect the mechanism and build a bridge between macro and micro views of Cold/Hot ZHENG as well as Cold/Hot herbs.

3.
Environ Entomol ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39349392

RESUMO

Anastatus orientalis Yang & Choi (Hymenoptera: Eupelmidae), an egg parasitoid of spotted lanternfly, Lycorma delicatula (White) (Hemiptera: Fulgoridae), has been documented emerging from host eggs in both autumn and spring, at the beginning and end of the period that spotted lanternfly eggs are present in the field, suggesting parasitoid-host specificity and synchrony. This study was designed to test whether, under conditions that simulate native and introduced ranges of spotted lanternfly, (a) A. orientalis has 2 and only 2 generations per year, (b) A. orientalis adults sometimes emerge when only nontarget species would be available for parasitization, and (c) emerging parasitoid adults can parasitize unhatched host eggs in the spring. Parasitized spotted lanternfly eggs were collected in 2019 and 2020 from Beijing, China and in 2020 and 2021 from Yantai, China. They were shipped for laboratory study in growth chambers programmed to simulate temperature and daylength for collection locations in China and in the invaded range in Pennsylvania, United States. Anastatus orientalis had a flexible lifecycle depending on environmental conditions and possibly genetic makeup, with 1-3 generations per year, and parasitoid emergence was not always synchronous with host egg availability. Additionally, given the cooler temperatures in Pennsylvania, autumn parasitoid emergence was often delayed until late October or November, no progeny were produced, and parasitoid populations died out. Anastatus orientalis does not exhibit host synchrony characteristics that would make it a good candidate for a classical biological control program.

4.
Sensors (Basel) ; 24(18)2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39338712

RESUMO

Using first-principles theory, this work purposes Ru-doped Janus WSSe (Ru-WSSe) monolayer as a potential gas sensor for detection of three typical gas species (CO, C2H2, and C2H4), in order to evaluate the operation status of the oil-immersed transformers. The Ru-doping behavior on the WSSe surface is analyzed, giving rise to the preferred doping site by the replacement of a Se atom with the formation energy of 0.01 eV. The gas adsorption of three gas species onto the Ru-WSSe monolayer is conducted, and chemisorption is identified for all three gas systems with the adsorption energy following the order: CO (-2.22 eV) > C2H2 (-2.01 eV) > C2H4 (-1.70 eV). Also, the modulated electronic properties and the frontier molecular orbital are investigated to uncover the sensing mechanism of Ru-WSSe monolayer upon three typical gases. Results reveal that the sensing responses of the Ru-WSSe monolayer, based on the variation of energy gap, to CO, C2H2, and C2H4 molecules are calculated to be 1.67 × 106, 2.10 × 105, and 9.61 × 103, respectively. Finally, the impact of the existence of O2 molecule for gas adsorption and sensing is also analyzed to uncover the potential of Ru-WSSe monolayer for practical application in the air atmosphere. The obtained high electrical responses manifest strong potential as a resistive sensor for detection of three gases. The findings hold practical implications for the development of novel gas sensing materials based on Janus WSSe monolayer. We anticipate that our results will inspire further research in this domain, particularly for applications in electrical engineering where the reliable detection of fault gases is paramount for maintaining the integrity and safety of power systems.

5.
Phytomedicine ; 134: 155993, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39244943

RESUMO

BACKGROUND: Chinese dragon's blood, the red resin of Dracaena cochinchinensis (Lour.) S. C. Chen., is widely used to treat cardiovascular and cerebrovascular diseases in China. Longxuetongluo Capsule (LTC) is a total phenolic compound extracted from Chinese dragon's blood, currently used in treating ischemic stroke. Myocardial injury can be aggravated after reperfusion of ischemic myocardium, which is called myocardial ischemia-reperfusion injury (MIRI), and the mechanism of MIRI is complex. However, the exact effect and mechanism of LTC on MIRI are still unclear. We explore the effect of LTC on alleviating MIRI based on mitochondrial dysfunction and oxidative stress. AIM OF THE STUDY: To explore the cardioprotective mechanism of LTC against MIRI. MATERIALS AND METHODS: A rat MIRI model was constructed through ligation of the left anterior descending coronary artery, and LTC was given continuously for 28 days before surgery. The H9c2 cardiomyocyte injury model was induced by oxygen-glucose deprivation/reperfusion (OGD/R), and LTC was given 24 h before OGD. Myocardial ischemia areas were detected with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cardiac histopathological changes were detected with hematoxylin-eosin (HE) staining. And biochemical indexes were detected with serum biochemical kit. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining and flow cytometry were used to detect apoptosis. Fluorescent probes were used to observe reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), Ca2+and other indexes. MitoTracker staining and immunofluorescence were used to observe the morphology of mitochondria and translocation of dynamin-related protein 1 (Drp1). Finally, immunohistochemistry and Western blotting were used to examine the expression of proteins related to apoptosis, mitochondrial fission and fusion and oxidative stress. RESULTS: LTC could ameliorate cardiac pathological changes, decrease myocardial infarct area and the content or level of relevant serum cardiac enzymes, indicating that LTC could alleviate MIRI. Meanwhile, LTC could inhibit cardiomyocyte apoptosis via regulating apoptosis-related protein expression, and it could restore mitochondrial morphology, maintain ΔΨm, inhibit mitochondrial ROS generation and Ca2+ accumulation, increase the expression of mitochondrial fusion protein 2 (Mfn2), decrease the level of phosphorylation dynamin-related protein 1 (p-Drp1), and regulate ATP synthesis, thereby significantly ameliorating mitochondrial dysfunction. Moreover, LTC significantly reduced the expression of NADPH oxidase 2 (NOX2), NADPH oxidase 4 (NOX4) and neutrophil cytosolic factor 2 (NOXA2/p67phox), and reduced ROS production. CONCLUSION: The study demonstrated that LTC could inhibit MIRI induced cardiomyocyte apoptosis by inhibiting ROS generation and mitochondrial dysfunction, and these fundings suggested that LTC can be used to alleviate MIRI, which provides a potential therapeutic approach for future treatment of MIRI.


Assuntos
Apoptose , Medicamentos de Ervas Chinesas , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Estresse Oxidativo , Ratos Sprague-Dawley , Animais , Estresse Oxidativo/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Masculino , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Linhagem Celular , Dinaminas/metabolismo
6.
Langmuir ; 40(40): 21067-21076, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39329510

RESUMO

Understanding the interlayer interaction between 2D layered structures is critical for the construction of various micro- and nanoscale functional devices. However, both the normal and the tangential interlayer interactions between 2D layered materials have rarely been studied simultaneously. In this work, an immersion and lift-up method is proposed to wrap a layer of graphene flakes onto a plasma-pretreated atomic force microscopy (AFM) nanoprobe for the measurements of interaction forces by AFM. The normal interactions (adhesion force and adhesion energy) and tangential interactions (friction force) between two different probes (Pt-coated probe and graphene-wrapped probe) and two different 2D graphene materials [graphene and graphene oxide (GO)] were systematically measured, respectively. The adhesion energies of Pt-GO, Pt-graphene, graphene-GO, and graphene-graphene were measured to be 0.72 ± 0.05, 0.41 ± 0.03, 0.19 ± 0.02, and 0.10 ± 0.02 J m-2, respectively. The graphene-graphene contact pair showed the lowest adhesion force (5.57 ± 1.03 nN) and adhesion energy (0.10 ± 0.02 J m-2), which was attributed to the strong covalent bonds and charge density distribution. The friction coefficients of Pt-GO, graphene-GO, Pt-graphene, and graphene-graphene were determined to be 0.38, 0.14, 0.054, and 0.013. The graphene-graphene tribo-pair exhibited a superlow friction state for a long time, which was attributed to incommensurate contact and weak van der Waals interactions. These findings provide a technical route to reveal the interlayer interactions of various 2D layered materials, which can be widely applied in microelectromechanical systems.

7.
Indian J Microbiol ; 64(3): 1035-1043, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39282164

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly infectious pathogen that poses a serious threat to human life and health. This study aimed to provide a scientific basis for the rational clinical use of antimicrobial drugs for treating MRSA infections and inform the development of preventive and control measures by analyzing the clinical distribution and resistance characteristics of MRSA in a hospital in Hebei China. To accomplish this, bacterial identification and drug sensitivity experiments were performed with 1858 Staphylococcus aureus (S. aureus) strains collected from a hospital from January 2018 to December 2022 using a phoenixTM-100 bacterial identification drug sensitivity analyzer. The experimental data were analyzed using WHONET 5.6 software, and the MRSA strains detected were analyzed for their clinical distribution and drug resistance. Of the 1858 S. aureus strains isolated, 429 were MRSA. Sputum samples had the highest MRSA detection rates (52.45%). Critical care medicine had the highest rate of MRSA (12.59%), followed by dermatology (9.79%). MRSA resistance to tetracycline increased by 13.9% over 5 years; resistance to quinupristin/dalfopristin also increased but remained low (1.9%). Resistance decreased to gentamicin, rifampicin, ciprofloxacin, and cotrimoxazole, though most significantly to erythromycin and clindamycin, exceeding 77% and 83%, respectively. No strains were resistant to vancomycin, teicoplanin, or linezolid, and drug resistance was most prevalent in patients ≥ 60 years old. This study will aid in improving the diagnosis and treatment of MRSA infections.

8.
Zookeys ; 1211: 251-348, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39290238

RESUMO

A checklist of 488 fall webworm Hyphantriacunea (Drury) natural enemies was compiled based on documentation in previous research across its world distribution, including 289 predators and 199 parasitoids. Predators in the checklist include 67 species from 17 families of Insecta, 1 species of Chilopoda, 183 species from 22 families of Arachnida, 1 species of Reptilia, 4 species from 2 families of Amphibia, 33 species from 18 families of Aves. In addition, the checklist includes fall webworm parasitoids from 18 families of Insecta. Among continents, 128 predators and 76 parasitoids were distributed in North America, 78 predators and 62 parasitoids in Asia, and 88 predators and 68 parasitoids in Europe.

9.
J Pharm Biomed Anal ; 250: 116407, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39151297

RESUMO

Reduning injection (RDN) is a traditional chinese medicine injection widely used in clinical practice. In this study, qualitative and quantitative analysis of RDN were conducted by UPLC-Orbitrap MS/MS simultaneously. Totally 118 compounds were identified and 34 compounds were quantified in RDN. The method with completed method validation proved the high sensitivity and efficiency of the method and it was applied to quantify compounds in RDN. Multivariate statistical analysis method selected 11 key variables that affect the content consistency of RDN. 20 batches with high biological potency were screened by cox-2 enzyme activity assay. Spectrum-effect relationship analysis and multivariate statistical analysis showed that 7 batches were high-quality selected after comprehensive quality evaluation and 9 compounds were key indicators for screening it. This strategy including fingerprint, qualitative analysis and multiple-component quantification could be well applied to modern quality evaluation of RDN, which could be valuable for the further quality control of more other traditional Chinese medicines.


Assuntos
Medicamentos de Ervas Chinesas , Controle de Qualidade , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/análise , Cromatografia Líquida de Alta Pressão/métodos , Análise Multivariada , Medicina Tradicional Chinesa/métodos , Reprodutibilidade dos Testes
10.
ACS Appl Mater Interfaces ; 16(35): 46872-46878, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39172985

RESUMO

With the rapid development of mobile communication technology, the POI (piezoelectric on insulator) structure has gained recognition in the field of RF filtering. However, transverse modes remain in the passband of corresponding surface acoustic wave (SAW) devices, which impedes their application in crowded spectra. This article introduces a groove configuration to suppress transverse modes for POI SAW resonators employing a 50°YX-LiTaO3/SiO2/Si multilayered structure. First, the response of conventional POI SAW resonators was calculated by the 3D periodic FEM method, and the results indicate that transverse modes caused by energy leakage to busbar regions are serious in POI SAW resonators. Then, the groove configuration was adopted to confine energy within the aperture region by reducing the velocity at the end of IDT electrodes, and the groove dimension was optimized to achieve a nearly spurious-free response in the passband. Finally, experimental results of fabricated one-port SAW resonators with optimal groove configuration were provided to validate the suppression of transverse modes and the enhancement of the Q factor in the POI SAW resonator.

11.
Lung Cancer ; 195: 107928, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39197359

RESUMO

PURPOSE: The mesothelin-targeting antibody-drug conjugate anetumab ravtansine was evaluated in combination with the programmed cell death-1 (PD-1) inhibitor pembrolizumab based on the common expression of mesothelin and reports of activity in mesothelioma. PATIENTS AND METHODS: A phase 1 safety run-in of the combination of anetumab ravtansine (6.5 mg/kg iv q3weeks) and pembrolizumab (200 mg, IV q3weeks) was conducted, followed by a phase 2 randomization to the combination or pembrolizumab alone at medical centers across the United States and Canada in the National Cancer Institute's Experimental Therapeutics Clinical Trials Network. Patients with pleural mesothelioma that expressed mesothelin and had previously received platinum-based therapy were eligible. RESULTS: In phase 1 (n = 12) only one dose limiting toxicity was observed and the rules for dose reduction were not met. In phase 2, there was no difference in the confirmed response rates between the combination group (n = 18, 2 partial responses [PR], 11 %) and the pembrolizumab group (n = 17, 1 PR, 6 %; z = -0.5523, p = 0.29116). The median PFS was 12.2 months (95 % CI 5.1-not evaluable [NE]) for the combination, and 3.9 months for pembrolizumab (95 % CI 2.1-NE)(HR=0.55, p = 0.20). Patients with high baseline levels of soluble mesothelin who received anetumab ravtansine had a median PFS of 5 months. CONCLUSIONS: The numeric difference in PFS between treatment groups was not statistically significant, likely related to a smaller than planned sample size. High levels of soluble mesothelin should potentially be considered to select against the use of mesothelin-targeting therapies in development that are neutralized by soluble mesothelin.


Assuntos
Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica , Mesotelioma , Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Feminino , Idoso , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Mesotelioma/tratamento farmacológico , Mesotelioma/mortalidade , Mesotelioma/patologia , Mesotelina , Maitansina/análogos & derivados , Maitansina/uso terapêutico , Maitansina/efeitos adversos , Idoso de 80 Anos ou mais , Neoplasias Pleurais/tratamento farmacológico , Neoplasias Pleurais/patologia , Neoplasias Pleurais/mortalidade , Proteínas Ligadas por GPI/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Imunoconjugados
12.
Adv Mater ; 36(41): e2406034, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39152937

RESUMO

Metallic lithium is the most competitive anode material for next-generation high-energy batteries. Nevertheless, the extensive volume expansion and uncontrolled Li dendrite growth of lithium metal not only cause potential safety hazards but also lead to low Coulombic efficiency and inferior cycling lifespan for Li metal batteries. Herein, a multifunctional dendrite-free composite anode (Li/SnS2) is proposed through an in situ melt-infusion strategy. In this configuration, the 3D cross-linked porous Li2S/Li22Sn5 framework facilitates the rapid penetration of electrolytes and accommodates the volume expansion during the repeated Li-plating process. Meanwhile, the lithiophilic Li2S phases with a low Li+ transport barrier ensure preferential Li deposition, effectively avoiding uneven electron distribution. Moreover, the Li22Sn5 electron conductors with appropriate Li+ bonding ability guarantee rapid charge transport and mass transfer. Most importantly, the steady multifunctional skeleton with sufficient inner interfaces (Li2S/Li22Sn5) in the whole electrode, not only realizes the redistribution of the localized free electron, contributing to the decomposition of Li clusters, but also induces a planar deposition model, thus restraining the generation of Li dendrites. Consequently, an unprecedented cyclability of over 6 500 h under an ultrahigh areal capacity of 10 mAh cm-2 and a current rate of 20 mA cm-2 is achieved for the prepared Li2S/Li22Sn5 composite anode. Moreover, the assembled Li/SnS2||LiFePO4 (LFP) pouch full-cells also demonstrate remarkable rate capability and a convincing cycling lifespan of more than 2 000 cycles at 2 C.

13.
Front Vet Sci ; 11: 1435827, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39044742

RESUMO

Canine circovirus (CanineCV) is a recently identified member of the Circoviridae family. Since its discovery in 2011, CanineCV has been detected in different countries worldwide, infecting both domestic and wild canids. The virus is potentially associated with gastrointestinal and respiratory illnesses. In 2016, CanineCV was reported in the southwestern region of Guangxi, China. However, its prevalence in other provinces in the Southwest region remained unknown. This study collected a total of 208 serum samples from domestic dogs in Sichuan, China in 2022 to investigate the prevalence of CanineCV. Among these samples, 26 tested positive for CanineCV, resulting in a positivity rate of 12.5%. Additionally, 12 strains were sequenced, 9 of which had a sequence length of 2,063 nucleotides (nt), 2 of the other threes had a length of 2,062 nts and another was 2,064 nt. Notably, a frameshift mutation was identified, resulting in a truncated ORF1 and the occurrence of a novel sequence comprised of 13 amino acids at the end of the replicate protein (Rep). This mutation could affect the replication cycle of the virus. Phylogenetic and evolutionary analyses revealed that the isolates belonged to the CanineCV-3 genotype and were prevalent in the Southeast and the Southwest regions of China, as well as in the neighboring countries alongside other strains of the same genotype. Collectively, this epidemiological investigation widens our understanding of the genetic diversity of CanineCV in Southwest China and provides insights into viral evolution.

14.
iScience ; 27(7): 110024, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38979010

RESUMO

Pyrrolidine (PyD) has an important impact on the environment and human health. However, there is currently no method for trace detection of PyD. Here, we successfully designed diaminomethylene-4H-pyran (1) as the first specific fluorescent probe for PyD. Only by adding PyD to probe 1, there is blue fluorescence at 455 nm, and the color of the solution changes from colorless to yellow. The detection limit is 1.12 × 10-6 M, and the response time is less than 5 min. Meanwhile, probe 1 can also sense the gaseous PyD and detect PyD in actual water samples. Moreover, due to the low biological toxicity, probe 1 can detect the exogenous PyD in zebrafish. The preliminary mechanism shows that probe 1 and PyD undergo a combination-type chemical reaction to generate a new substance 1-PyD. Therefore, the 100% atom utilization reaction enables probe 1 to exhibit specific adsorption and removal of PyD.

15.
J Clin Oncol ; 42(25): 3033-3046, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38954785

RESUMO

PURPOSE: Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts. METHODS: This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier: NCT02496208). RESULTS: The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients. CONCLUSION: CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.


Assuntos
Anilidas , Protocolos de Quimioterapia Combinada Antineoplásica , Ipilimumab , Nivolumabe , Piridinas , Neoplasias Urogenitais , Humanos , Masculino , Anilidas/uso terapêutico , Anilidas/efeitos adversos , Ipilimumab/uso terapêutico , Ipilimumab/efeitos adversos , Ipilimumab/administração & dosagem , Nivolumabe/uso terapêutico , Nivolumabe/efeitos adversos , Piridinas/uso terapêutico , Piridinas/efeitos adversos , Pessoa de Meia-Idade , Idoso , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Neoplasias Urogenitais/tratamento farmacológico , Neoplasias Urogenitais/patologia , Idoso de 80 Anos ou mais , Intervalo Livre de Progressão
16.
Biomed Pharmacother ; 176: 116908, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38850668

RESUMO

Non-alcoholic fatty liver disease (NAFLD), particularly advanced non-alcoholic steatohepatitis (NASH), leads to irreversible liver damage. This study investigated the therapeutic effects and potential mechanism of a novel extract from traditional Chinese medicine Alisma orientale (Sam.) Juzep (AE) on free fatty acid (FFA)-induced HepG2 cell model and high-fat diet (HFD) + carbon tetrachloride (CCl4)-induced mouse model of NASH. C57BL/6 J mice were fed a HFD for 10 weeks. Subsequently, the mice were injected with CCl4 to induce NASH and simultaneously treated with AE at daily doses of 50, 100, and 200 mg/kg for 4 weeks. At the end of the treatment, animals were fasted for 12 h and then sacrificed. Blood samples and liver tissues were collected for analysis. Lipid profiles, oxidative stress, and histopathology were examined. Additionally, a polymerase chain reaction (PCR) array was used to predict the molecular targets and potential mechanisms involved, which were further validated in vivo and in vitro. The results demonstrated that AE reversed liver damage (plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatocyte ballooning, hepatic steatosis, and NAS score), the accumulation of hepatic lipids (TG and TC), and oxidative stress (MDA and GSH). PCR array analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that AE protects against NASH by regulating the adipocytokine signaling pathway and influencing nuclear receptors such as PPARα. Furthermore, AE increased the expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PPARGC1α) and reversed the decreased expression of PPARα in NASH mice. Moreover, in HepG2 cells, AE reduced FFA-induced lipid accumulation and oxidative stress, which was dependent on PPARα up-regulation. Overall, our findings suggest that AE may serve as a potential therapeutic approach for NASH by inhibiting lipid accumulation and reducing oxidative stress specifically through the PPARα pathway.


Assuntos
Alisma , Dieta Hiperlipídica , Hepatopatia Gordurosa não Alcoólica , Extratos Vegetais , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Alisma/química , Tetracloreto de Carbono , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Células Hep G2 , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , PPAR alfa/metabolismo , Transdução de Sinais/efeitos dos fármacos
17.
Front Pharmacol ; 15: 1393693, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855753

RESUMO

Colorectal cancer is a common malignant tumor with high mortality, for which chemotherapy resistance is one of the main reasons. The high expression of ABCG2 in the cancer cells and expulsion of anticancer drugs directly cause multidrug resistance (MDR). Therefore, the development of new ABCG2 inhibitors that block the active causes of MDR may provide a strategy for the treatment of colorectal cancer. In this study, we find that dorsomorphin (also known as compound C or BML-275) potently inhibits the transporter activity of ABCG2, thereby preserving the chemotherapeutic agents mitoxantrone and doxorubicin to antagonize MDR in ABCG2-overexpressing colorectal cancer cells. Additionally, dorsomorphin does not alter ABCG2 protein expression. The results of molecular docking studies show that dorsomorphin is bound stably to the ABCG2-binding pocket, suggesting that dorsomorphin is a potent ABCG2 inhibitor that attenuates ABCG2-mediated MDR in colorectal cancer.

18.
Materials (Basel) ; 17(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38893935

RESUMO

The inferior mechanical performance and freeze-thaw (FT) resistance of recycled concrete are mostly due to the significant water absorption and porosity of recycled coarse particles. In this study, different dosages of zeolite powder were used in recycled concrete. A series of macroscopic tests were used to evaluate the workability and FT durability of zeolite powder-modified recycled concrete (ZPRC). X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to reveal the micro-mechanisms of FT resistance in ZPRC. The results show that the increase in zeolite powder content leads to a decrease in the slump and water absorption of ZPRC. Additionally, ZPRC with 10% zeolite powder has superior mechanical characteristics and tolerance to FT conditions. The higher strength and FT resistance of the ZPRC can be attributed to the particle-filling effect, water storage function, and pozzolanic reaction of zeolite powder, which results in a denser microstructure. The particle-filling effect of zeolite powder promotes the reduction of surface pores in recycled coarse aggregates (RCAs). The water storage function of zeolite powder can provide water for the secondary hydration of cement particles while reducing the free water content in ZPRC. The pozzolanic reaction of zeolite powder can also promote the generation of hydrated calcium silicate and anorthite, thereby making the microstructure of ZPRC more compact. These results provide theoretical guidance for the engineering application of recycled concrete in cold regions.

19.
Sci Rep ; 14(1): 13917, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886497

RESUMO

Chinese rose (Rosa chinensis) is an important ornamental plant, with economic, cultural, and symbolic significance. During the application of outdoor greening, adverse environments such as high temperature and drought are often encountered, which affect its application scope and ornamental quality. The starch phosphorylase (Pho) gene family participate in the synthesis and decomposition of starch, not only related to plant energy metabolism, but also plays an important role in plant stress resistance. The role of Pho in combating salinity and high temperature stress in R. chinensis remains unknown. In this work, 4 Phos from R. chinensis were detected with Pfam number of Pho (PF00343.23) and predicted by homolog-based prediction (HBP). The Phos are characterized by sequence lengths of 821 to 997 bp, and the proteins are predicted to subcellularly located in the plastid and cytoplasm. The regulatory regions of the Phos contain abundant stress and phytohormone-responsive cis-acting elements. Based on transcriptome analysis, the Phos were found to respond to abiotic stress factors such as drought, salinity, high temperature, and plant phytohormone of jasmonic acid and salicylic acid. The response of Phos to abiotic stress factors such as salinity and high temperature was confirmed by qRT-PCR analysis. To evaluate the genetic characteristics of Phos, a total of 69 Phos from 17 species were analyzed and then classified into 3 groups in phylogenetic tree. The collinearity analysis of Phos in R. chinensis and other species was conducted for the first time. This work provides a view of evolution for the Pho gene family and indicates that Phos play an important role in abiotic stress response of R. chinensis.


Assuntos
Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Rosa , Amido Fosforilase , Estresse Fisiológico , Estresse Fisiológico/genética , Rosa/genética , Rosa/enzimologia , Rosa/metabolismo , Amido Fosforilase/genética , Amido Fosforilase/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica , Secas , Genoma de Planta , Salinidade
20.
Am J Surg ; 234: 172-178, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38755026

RESUMO

BACKGROUND: Vessels encapsulating tumor clusters (VETC) pattern of hepatocellular carcinoma (HCC) are associated with unfavorable prognosis. This study aimed to establish a nomogram model to predict VETC patterns based on preoperative CT imaging features. PATIENTS AND METHODS: Patients who underwent surgical resection between January 1, 2016 and August 31, 2022 were retrospectively included. Predictors associated with VETC pattern were determined by using logistic regression analyses, and a nomogram model was constructed. Prognostic factors associated with recurrence-free survival (RFS) after surgical resection were identified by using Cox regression analyses. RESULTS: A total of 84 patients were included for CT analysis. All patients underwent radical surgical resection. AST/ALT >1.07(odds ratio [OR], 4.91; 95 â€‹% CI: 1.11, 21.68; P â€‹< â€‹0.05), intratumoral necrosis (OR, 4.99; 95 â€‹% CI: 1.25, 19.99; P â€‹< â€‹0.05) and enhancing capsule (OR, 3.32; 95 â€‹% CI: 1.27, 8.94; P â€‹< â€‹0.05) were independent predictors of VETC pattern. These features were used for the construction of nomogram model, which showed comparable prediction performance, with AUC value of 0.767 (95%CI [0.662, 0.852]). CK19 status (Hazard ratio [HR], 2.02; 95 â€‹% CI: 1.06, 3.86; P â€‹< â€‹0.05), the number of tumors (HR, 3.31; 95 â€‹% CI: 1.47, 7.45; P â€‹< â€‹0.05) and VETC pattern (HR, 2.52; 95 â€‹% CI: 1.31, 4.86; P â€‹< â€‹0.05) were independent predictors of postoperative RFS. CONCLUSION: A nomogram model based on preoperative CT imaging features could be used for the characterization of VETC pattern, and has prognostic significance for postoperative RFS in patients with HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nomogramas , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Prognóstico , Hepatectomia , Idoso , Valor Preditivo dos Testes
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