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1.
Adv Sci (Weinh) ; : e2402610, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38887865

RESUMO

Here, an approach to produce a hierarchical porous Fe-N-C@TABOH catalyst with densely accessible high intrinsic active FeNx sites is proposed. The method involves a single-step pyrolysis of Zn/Fe-zeolitic imidazolate framework (Zn/Fe-ZIF-H) with tetrabutylammonium hydroxide (TABOH) micelles, which is obtained by utilizing TABOH as a structural template and electronic mediator at room temperature for a brief duration of 16 min. Notably, the yield of Zn/Fe-ZIF-H is 3.5 times that of Zn/Fe-ZIF-N prepared by conventional method. Results indicate that in addition to expediting synthesis and increasing yield of the Zn/Fe-ZIF-H, the TABOH induces a hierarchical porous structure and fosters the formation of more and higher intrinsic active FeNx moieties in Fex-N-C@TABOH, showing that TABOH is a multifunctional template. Crucially, the increased mesoporosity/external surface area and optimized microenvironment of Fe-N-C@TABOH significantly enhance ORR activity by facilitating the formation of high intrinsic active FeNx sites, increasing accessible FeNx sites, and reducing mass transfer resistance. Through structure tailoring and microenvironment optimization, the resulting Fe-N-C@TABOH exhibits superior ORR performance. DFT calculation further validates that the synergistic effect of these two factors leads to low ORR barrier and optimized *OH adsorption energy. This study underscores the importance of structure and electronic engineering in the development of highly active ORR catalysts.

2.
Vet Med Sci ; 10(4): e1468, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38879882

RESUMO

BACKGROUND: Piroplasmosis is a common and prevalent tick-borne disease that affects equids. OBJECTIVES: To determine the infection and molecular characteristics of the piroplasms in donkeys from Xinjiang, northwestern China, we undertook a cross sectional study by collecting representative samples across several counties within the region. METHODS: A total of 344 blood samples were collected from adult domestic donkeys from 13 counties in Xinjiang. PCR was conducted to test for T. equi and B. caballi in the blood samples based on the equine merozoite antigen-1 (Ema-1) gene and the 48 kDa rhoptry protein (BC48) gene, respectively. RESULTS: Sixteen blood samples tested positive for piroplasms and the overall infection rate was 4.7% (16/344). Seven of the 13 counties were positive for piroplasms. Among the 16 piroplasm-positive samples, 15 were singly infected with T. equi with an infection rate of 4.4% (15/344), and coinfection with T. equi and B. caballi was detected in one sample (0.3%, 1/344) from Wushi. Four T. equi sequence genotypes were identified and grouped into different branches of the evolutionary trees. CONCLUSION: These findings suggest that the infection rate of piroplasms is low in domestic donkeys in southern Xinjiang and that T. equi genotypes have a regional distribution.


Assuntos
Babesia , Babesiose , Equidae , Theileria , Animais , Equidae/parasitologia , China/epidemiologia , Babesiose/epidemiologia , Babesiose/parasitologia , Babesia/isolamento & purificação , Babesia/genética , Babesia/classificação , Theileria/genética , Theileria/isolamento & purificação , Estudos Transversais , Feminino , Masculino , Prevalência , Theileriose/epidemiologia , Theileriose/parasitologia
3.
Environ Pollut ; : 124375, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38880327

RESUMO

Water pollution caused by antibiotics and synthetic dyes and imminent energy crises due to limited fossil fuel resources are issues of contemporary decades. Herein, we address them by enabling the multifunctionality in dual Z-scheme MoS2/WO3-x/AgBiS2 across photolysis, photo Fenton-like, and night catalysis. Defect, basal, and facet-engineered WO3-x is modified with MoS2 and AgBiS2, which extended its photoresponse from the UV-NIR region, inhibited carrier recombination, and reduced carrier transfer resistance. The electric field rearrangement leads to a flow of electrons from MoS2 and AgBiS2 to WO3-x and intensifies the electron population, which is crucial for night catalysis. When MoS2/WO3-x/AgBiS2 was employed against doxycycline hydrochloride (DOXH), it removed 95.65, 81.11, and 77.92 % of DOXH in 100 minutes during photo-Fenton (PFR), night-Fenton (NFR), and photocatalytic (PCR) reactions, respectively. It also effectively removed 91.91, 98.17, 99.01, and 98.99 % of rhodamine B (RhB), Congo red (CR), methylene blue (MB), and methylene orange (MO) in Fenton reactions, respectively. ESR analysis consolidates the ROS generation feature of MoS2/WO3-x/AgBiS2 using H2O2 with and without irradiation. This work provides a strategy to eliminate the deficiencies of WO3-x and is conducive to the evolution of applications seeking to combat environmental and energy crises.

4.
Vet Microbiol ; 293: 110089, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38678845

RESUMO

Brucellosis is a zoonotic disease that affects wild and domestic animals. It is caused by members of the bacterial genus Brucella. Guanylate-binding protein 1 (GBP1) is associated with microbial infections. However, the role of GBP1 during Brucella infection remains unclear. This investigation aimed to identify the association of GBP1 with brucellosis. Results showed that Brucella infection induced GBP1 upregulation in RAW 264.7 murine macrophages. Small interfering GBP1 targeting RNAs were utilized to explore how GBP1 regulates the survival of Brucella intracellularly. Results revealed that GBP1 knockdown promoted Brucella's survival ability, activated Nod-like receptor (NLR) containing a pyrin domain 3 (NLRP3) and absent in melanoma 2 (AIM2) inflammatory corpuscles, and induced pro-inflammatory cytokines IFN-γ and IL-1ß. Furthermore, Brucella stimulated the expression of GBP1 in bone marrow-derived macrophages (BMDMs) and mice. During the inhibition of GBP1 in BMDMs, the intracellular growth of Brucella increased. In comparison, GBP1 downregulation enhanced the accumulation of Brucella-induced reactive oxygen species (ROS) in macrophages. Overall, the data indicate a significant role of GBP1 in regulating brucellosis and suggest the function underlying its suppressive effect on the survival and growth of Brucella intracellularly.


Assuntos
Brucelose , Proteínas de Ligação ao GTP , Macrófagos , Animais , Camundongos , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Macrófagos/microbiologia , Brucelose/microbiologia , Células RAW 264.7 , Brucella/genética , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos C57BL
5.
Comput Biol Med ; 171: 108229, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38447500

RESUMO

Conventional COVID-19 testing methods have some flaws: they are expensive and time-consuming. Chest X-ray (CXR) diagnostic approaches can alleviate these flaws to some extent. However, there is no accurate and practical automatic diagnostic framework with good interpretability. The application of artificial intelligence (AI) technology to medical radiography can help to accurately detect the disease, reduce the burden on healthcare organizations, and provide good interpretability. Therefore, this study proposes a new deep neural network (CNN) based on CXR for COVID-19 diagnosis - CodeNet. This method uses contrastive learning to make full use of latent image data to enhance the model's ability to extract features and generalize across different data domains. On the evaluation dataset, the proposed method achieves an accuracy as high as 94.20%, outperforming several other existing methods used for comparison. Ablation studies validate the efficacy of the proposed method, while interpretability analysis shows that the method can effectively guide clinical professionals. This work demonstrates the superior detection performance of a CNN using contrastive learning techniques on CXR images, paving the way for computer vision and artificial intelligence technologies to leverage massive medical data for disease diagnosis.


Assuntos
COVID-19 , Aprendizado Profundo , Humanos , COVID-19/diagnóstico por imagem , Teste para COVID-19 , Inteligência Artificial , Redes Neurais de Computação
6.
J Colloid Interface Sci ; 662: 250-262, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38350348

RESUMO

Tetracycline (TC) antibiotics and dyes are the prevalent water contaminants, and their removal from the water through photocatalysis is a plausible approach. However, most semiconductors in their pristine form need to be improved to be exploited in photocatalysis owing to poor photoresponse, intense carrier recombination, and inertness without irradiation. Herein, we demonstrate the modification of defective WO3-x by rGO and AgBiS2 in the form of WO3-x/rGO/AgBiS2 (R2). It exploits the superior conductivity and synergism of rGO to inhibit carrier recombination; thereby, Z-scheme heterojunction with AgBiS2 provides high redox potential. Defects in WO3-x enable electron (e-) storage in R2, which decomposes H2O2 to generate ROS without irradiation. Owing to these essences and broad-spectrum response, it removed 93.72, 82.77, and 84.82% of TC during photo-Fenton (PFR), night-Fenton (NFR), and photocatalytic (PCR) reactions, respectively. Its removal rates reached 94.74, 81.54, and 87.50% against rhodamine B (RhB) during PFR, NFR, and PCR, respectively. It is superior to memory catalysis (MC) and conventional Fenton reactions (CFR) because it can perform without and with irradiation across a broader pH range. So, this work is conducive to designing WO3-x-based catalysts to combat environmental and energy crises.

7.
iScience ; 27(2): 108873, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38318371

RESUMO

Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related death worldwide. Epithelial-mesenchymal transition (EMT) plays an important role in malignant tumor progression. Recently, accumulating evidence has shown that autophagy is involved in the regulation of EMT-induced migration. Therefore, the exploration of targets to inhibit EMT by targeting autophagy is important. In this study, we found that OVO-like zinc finger 2 (OVOL2) may be a key target for regulating autophagy-induced EMT. Firstly, we found that OVOL2 expression was dramatically downregulated in LUAD. Low expression of OVOL2 is an indicator of poor prognosis in LUAD. In vitro experiments have shown that downregulation of OVOL2 expression induces EMT, thereby promoting malignant biological behavior, such as proliferation, migration, and invasion of LUAD cells. Interestingly, autophagy is a key step in regulating OVOL2 and inducing EMT. Furthermore, OVOL2 regulates autophagy through the MAPK signaling pathway, ultimately inhibiting the malignant progression of LUAD.

9.
Brain Imaging Behav ; 18(1): 73-82, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37874444

RESUMO

Type 2 diabetes mellitus (T2DM) and cognitive dysfunction are highly prevalent disorders worldwide. Although visual network (VN) alteration and functional-structural coupling are potential warning factors for mild cognitive impairment (MCI) in T2DM patients, the relationship between the three in T2DM without MCI is unclear. Thirty T2DM patients without MCI and twenty-nine healthy controls (HC) were prospectively enrolled. Visual components (VC) were estimated by independent component analysis (ICA). Degree centrality (DC), amplitude of low frequency fluctuation (ALFF) and fractional anisotropy (FA) were established to reflect functional and structural characteristics in these VCs respectively. Functional-structural coupling coefficients were further evaluated using combined FA and DC or ALFF. Partial correlations were performed among neuroimaging indicators and neuropsychological scores and clinical variables. Three VCs were selected using group ICA. Deteriorated DC, ALFF and DC-FA coefficients in the VC1 were observed in the T2DM group compared with the HC group, while FA and ALFF-FA coefficients in these three VCs showed no significant differences. In the T2DM group, DC in the VC1 positively correlated with 2 dimensions in the California Verbal Learning Test, including Trial 4 and Total trial 1-5. The impaired DC-FA coefficients in the VC1 markedly affected the Total perseverative responses % of the Wisconsin Card Sorting Test. These findings indicate that DC and DC-FA coefficients in VN may be potential imaging biomarkers revealing early cognitive deficits in T2DM.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Humanos , Imageamento por Ressonância Magnética , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Neuroimagem
10.
Biotechnol Bioeng ; 121(2): 696-709, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37994547

RESUMO

Intensified fed-batch (IFB), a popular cell culture intensification strategy, has been widely used for productivity improvement through high density inoculation followed by fed-batch cultivation. However, such an intensification strategy may counterproductively induce rapidly progressing cell apoptosis and difficult-to-sustain productivity. To improve culture performance, we developed a novel cell culture process intermittent-perfusion fed-batch (IPFB) which incorporates one single or multiple cycles of intermittent perfusion during an IFB process for better sustained cellular and metabolic behaviors and notably improved productivity. Unlike continuous perfusion or other semi-continuous processes such as hybrid perfusion fed-batch with only early-stage perfusion, IPFB applies limited times of intermittent perfusion in the mid-to-late stage of production and still inherits bolus feedings on nonperfusion days as in a fed-batch culture. Compared to IFB, an average titer increase of ~45% was obtained in eight recombinant CHO cell lines studied. Beyond IPFB, ultra-intensified IPFB (UI-IPFB) was designed with a markedly elevated seeding density of 20-80 × 106 cell/mL, achieved through the conventional alternating tangential flow filtration (ATF) perfusion expansion followed with a cell culture concentration step using the same ATF system. With UI-IPFB, up to ~6 folds of traditional fed-batch and ~3 folds of IFB productivity were achieved. Furthermore, the application grounded in these two novel processes showed broad-based feasibility in multiple cell lines and products of interest, and was proven to be effective in cost of goods reduction and readily scalable to a larger scale in existing facilities.


Assuntos
Técnicas de Cultura Celular por Lotes , Reatores Biológicos , Cricetinae , Animais , Cricetulus , Células CHO , Perfusão
11.
Front Neurosci ; 17: 1301778, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38125399

RESUMO

Background: Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are aging related diseases with high incidence. Because of the correlation of incidence rate and some possible mechanisms of comorbidity, the two diseases have been studied in combination by many researchers, and even some scholars call AD type 3 diabetes. But the relationship between the two is still controversial. Methods: This study used seed-based d mapping software to conduct a meta-analysis of the whole brain resting state functional magnetic resonance imaging (rs-fMRI) study, exploring the differences in amplitude low-frequency fluctuation (ALFF) and cerebral blood flow (CBF) between patients (AD or T2DM) and healthy controls (HCs), and searching for neuroimaging evidence that can explain the relationship between the two diseases. Results: The final study included 22 datasets of ALFF and 22 datasets of CBF. The results of T2DM group showed that ALFF increased in both cerebellum and left inferior temporal gyrus regions, but decreased in left middle occipital gyrus, right inferior occipital gyrus, and left anterior central gyrus regions. In the T2DM group, CBF increased in the right supplementary motor area, while decreased in the middle occipital gyrus and inferior parietal gyrus. The results of the AD group showed that the ALFF increased in the right cerebellum, right hippocampus, and right striatum, while decreased in the precuneus gyrus and right superior temporal gyrus. In the AD group, CBF in the anterior precuneus gyrus and inferior parietal gyrus decreased. Multimodal analysis within a disease showed that ALFF and CBF both decreased in the occipital lobe of the T2DM group and in the precuneus and parietal lobe of the AD group. In addition, there was a common decrease of CBF in the right middle occipital gyrus in both groups. Conclusion: Based on neuroimaging evidence, we believe that T2DM and AD are two diseases with their respective characteristics of central nervous activity and cerebral perfusion. The changes in CBF between the two diseases partially overlap, which is consistent with their respective clinical characteristics and also indicates a close relationship between them. Systematic review registration: PROSPERO [CRD42022370014].

12.
Int Microbiol ; 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37982990

RESUMO

The intestinal microbiota plays significant role in the physiology and functioning of host organisms. However, there is limited knowledge of the composition and evolution of microbiota-host relationships from wild ancestors to modern domesticated species. In this study, the 16S rRNA gene V3-V4 in the intestinal contents of different pig breeds was analyzed and was compared using high-throughput sequencing. This identified 18 323 amplicon sequence variants, of which the Firmicutes and Actinobacteria phyla and Bifidobacterium and Allobaculum genera were most prevalent in wild pigs (WP). In contrast, Proteobacteria and Firmicutes predominated in Chinese Shanxi Black pigs (CSB), while Firmicutes were the most prevalent phylum in Large White pigs (LW) and Iberian pigs (IB), followed by Bacteroidetes in IB and Proteobacteria in LW. At the genus level, Shigella and Lactobacillus were most prevalent in CSB and LW, while Actinobacillus and Sarcina predominated in IB. Differential gene expression together with phylogenetic and functional analyses indicated significant differences in the relative abundance of microbial taxa between different pig breeds. Although many microbial taxa were common to both wild and domestic pigs, significant diversification was observed in bacterial genes that potentially influence host phenotypic traits. Overall, these findings suggested that both the composition and functions of the microbiota were closely associated with domestication and the evolutionary changes in the host. The members of the microbial communities were vertically transmitted in pigs, with evidence of co-evolution of both the hosts and their intestinal microbial communities. These results enhance our understanding and appreciation of the complex interactions between intestinal microbes and hosts and highlight the importance of applying this knowledge in agricultural and microbiological research.

13.
Int J Mol Sci ; 24(15)2023 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-37569377

RESUMO

Sonodynamic therapy (SDT) is an emerging non-invasive cancer treatment method in the field of nanomedicine, which has the advantages of deep penetration, good therapeutic efficacy, and minimal damage to normal tissues. Sonosensitizers play a crucial role in the process of SDT, as their structure and properties directly determine the treatment outcome. Inorganic sonosensitizers, with their high stability and longer circulation time in the human body, have great potential in SDT. In this review, the possible mechanisms of SDT including the ultrasonic cavitation, reactive oxygen species generation, and activation of immunity are briefly discussed. Then, the latest research progress on inorganic sonosensitizers is systematically summarized. Subsequently, strategies for optimizing treatment efficacy are introduced, including combination therapy and image-guided therapy. The challenges and future prospects of sonodynamic therapy are discussed. It is hoped that this review will provide some guidance for the screening of inorganic sonosensitizers.


Assuntos
Neoplasias , Terapia por Ultrassom , Humanos , Neoplasias/terapia , Neoplasias/diagnóstico , Terapia Combinada , Nanomedicina Teranóstica , Nanomedicina , Espécies Reativas de Oxigênio
14.
Nat Commun ; 14(1): 5093, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37607912

RESUMO

Antimicrobial peptides (AMPs) are important mediators of intestinal immune surveillance. However, the regional heterogeneity of AMPs and its regulatory mechanisms remain obscure. Here, we clarified the regional heterogeneity of intestinal AMPs at the single-cell level, and revealed a cross-lineages AMP regulation mechanism that bile acid dependent transcription factors (BATFs), NR1H4, NR1H3 and VDR, regulate AMPs through a ligand-independent manner. Bile acids regulate AMPs by perturbing cell differentiation rather than activating BATFs signaling. Chromatin accessibility determines the potential of BATFs to regulate AMPs at the pre-transcriptional level, thus shaping the regional heterogeneity of AMPs. The BATFs-AMPs axis also participates in the establishment of intestinal antimicrobial barriers of fetuses and the defects of antibacterial ability during Crohn's disease. Overall, BATFs and chromatin accessibility play essential roles in shaping the regional heterogeneity of AMPs at pre- and postnatal stages, as well as in maintenance of antimicrobial immunity during homeostasis and disease.


Assuntos
Cromatina , Intestinos , Cromatina/genética , Peptídeos Antimicrobianos , Ácidos e Sais Biliares , Fatores de Transcrição/genética
15.
Nat Commun ; 14(1): 3701, 2023 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-37349302

RESUMO

Non-aqueous sodium-ion batteries (SiBs) are a viable electrochemical energy storage system for grid storage. However, the practical development of SiBs is hindered mainly by the sluggish kinetics and interfacial instability of positive-electrode active materials, such as polyanion-type iron-based sulfates, at high voltage. Here, to circumvent these issues, we proposed the multiscale interface engineering of Na2.26Fe1.87(SO4)3, where bulk heterostructure and exposed crystal plane were tuned to improve the Na-ion storage performance. Physicochemical characterizations and theoretical calculations suggested that the heterostructure of Na6Fe(SO4)4 phase facilitated ionic kinetics by densifying Na-ion migration channels and lowering energy barriers. The (11-2) plane of Na2.26Fe1.87(SO4)3 promoted the adsorption of the electrolyte solution ClO4- anions and fluoroethylene carbonate molecules, which formed an inorganic-rich Na-ion conductive interphase at the positive electrode. When tested in combination with a presodiated FeS/carbon-based negative electrode in laboratory- scale single-layer pouch cell configuration, the Na2.26Fe1.87(SO4)3-based positive electrode enables an initial discharge capacity of about 83.9 mAh g-1, an average cell discharge voltage of 2.35 V and a specific capacity retention of around 97% after 40 cycles at 24 mA g-1 and 25 °C.


Assuntos
Ferro , Sulfatos , Adsorção , Eletrodos
16.
J Proteomics ; 283-284: 104938, 2023 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-37230328

RESUMO

GntR10 is a transcriptional regulator in Brucella. Nuclear factor-kappa B (NF-κB) is involved in many cellular activities, playing major roles in orchestrating the expression of inflammatory genes and regulating protein function that is essential for pathogenic bacteria during infection. GntR10 deletion was previously found to affect the growth and the virulence of Brucella and expression levels of target genes of GntR10 in mice. However, the mechanisms of affection of NF-κB regulated by Brucella GntR10 are still unclear. Here, GntR10 deletion could regulate the expression of LuxR-type transcriptional activators (VjbR and BlxR) of the quorum sensing system (QSS) and type IV secretion system (T4SS) effectors (BspE and BspF) of Brucella. It could further inhibit the activation of the regulator NF-κB and affect the virulence of Brucella. This research provides new insights into the designing of Brucella vaccines and the screening of drug targets. SIGNIFICANCE: Transcriptional regulators are predominant bacterial signal transduction factors. The pathogenicity of Brucella is due to its ability to regulate the expression of virulence related genes including quorum sensing system (QSS) and type IV secretion system (T4SS). Transcriptional regulators are designed to regulate gene expression and enact an appropriate adaptive physiological response. Here, we show that Brucella transcriptional regulator GntR10 regulated the expression of QSS and T4SS effectors, which affected the activation of NF-κB.


Assuntos
Brucella , Camundongos , Animais , Brucella/metabolismo , NF-kappa B/metabolismo , Sistemas de Secreção Tipo IV/metabolismo , Percepção de Quorum/genética , Regulação Bacteriana da Expressão Gênica , Proteínas de Bactérias/metabolismo
17.
Nat Commun ; 14(1): 1487, 2023 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-36932071

RESUMO

High entropy oxides (HEOs) with chemically disordered multi-cation structure attract intensive interest as negative electrode materials for battery applications. The outstanding electrochemical performance has been attributed to the high-entropy stabilization and the so-called 'cocktail effect'. However, the configurational entropy of the HEO, which is thermodynamically only metastable at room-temperature, is insufficient to drive the structural reversibility during conversion-type battery reaction, and the 'cocktail effect' has not been explained thus far. This work unveils the multi-cations synergy of the HEO Mg0.2Co0.2Ni0.2Cu0.2Zn0.2O at atomic and nanoscale during electrochemical reaction and explains the 'cocktail effect'. The more electronegative elements form an electrochemically inert 3-dimensional metallic nano-network enabling electron transport. The electrochemical inactive cation stabilizes an oxide nanophase, which is semi-coherent with the metallic phase and accommodates Li+ ions. This self-assembled nanostructure enables stable cycling of micron-sized particles, which bypasses the need for nanoscale pre-modification required for conventional metal oxides in battery applications. This demonstrates elemental diversity is the key for optimizing multi-cation electrode materials.

18.
Technol Cancer Res Treat ; 22: 15330338231152350, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36727222

RESUMO

Background: Chemotherapy combined with antivascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor monoclonal antibodies is the most promising approach to prolong survival and improve the quality of life of patients with unresectable metastatic colorectal cancer (mCRC). Anlotinib is an oral antiangiogenic tyrosine kinase inhibitor that targets VEGF receptors 1/2/3, fibroblast growth factor receptors 1-4, and platelet-derived growth factor receptors a/ß. Since anlotinib combined with oxaliplatin and capecitabine (CAPEOX) as a first-line treatment was previously shown to be effective and safe for patients with RAS/BRAF wild-type (WT) mCRC, we designed this randomized, open-label, parallel-group, non-inferiority, phase III study to evaluate the efficacy and safety of anlotinib plus CAPEOX versus bevacizumab plus CAPEOX in patients with RAS/BRAF WT mCRC. Methods/design: The primary inclusion criteria are Eastern Cooperative Oncology Group performance status 0/1, confirmed RAS/BRAF WT colorectal adenocarcinoma, and unresectable metastases assessed by a multidisciplinary team. The main exclusion criteria are as follows: high microsatellite instability or deficient mismatch repair status, resectable or potentially resectable metastases, and previous systemic therapy for mCRC. A total of 698 patients will be randomized into the anlotinib and bevacizumab groups in a 1:1 ratio. Patients will receive 4 to 8 cycles of induction therapy (CAPEOX plus anlotinib or bevacizumab), followed by maintenance treatment (capecitabine plus anlotinib or bevacizumab) until disease progression or unacceptable toxicity. Progression-free survival (PFS) assessed by an independent review committee is the primary endpoint, whereas investigator-assessed PFS, overall survival, objective response rate, disease control rate, duration of response, resection rate of liver metastases, quality of life, and safety are the secondary endpoints. Enrollment commenced in May 2021. Discussion: A prospective, randomized, phase III trial will provide a meaningful comparison of the efficacy and safety of anlotinib plus CAPEOX with standard treatment for patients with unresectable RAS/BRAF WT mCRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Neoplasias Colorretais , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Capecitabina , Ensaios Clínicos Fase III como Assunto , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Estudos Prospectivos , Proteínas Proto-Oncogênicas B-raf/genética , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Chem Commun (Camb) ; 59(16): 2311-2314, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36748302

RESUMO

Water-soluble Ag-doped InP/ZnS quantum dots (QDs) with high photoluminescence quantum yield were synthesized and characterized. Their maximum two- and three-photon absorption cross sections are determined as ∼1.7 × 104 GM at 820 nm and ∼1.7 × 10-76 cm6 s2 photon-2 at 1260 nm. Importantly, for the first time, we demonstrated that Ag-doped InP/ZnS QDs can be used for type-I photodynamic therapy and are more suitable for the hypoxic environment of tumors.

20.
Anal Chem ; 95(4): 2129-2133, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36576397

RESUMO

Three-dimensional nondestructive, nanoresolution, and in situ visualization of protein spatial localization in a large, thick single cell remains challenging. In this study, we designed a multifunctional iron oxide (Fe@BFK) nanoprobe that possesses fluorescence and hard X-ray imaging signals. This probe can specifically target the human epidermal growth factor receptor 2 (HER2) protein and help optimize the label condition and selection of suitable samples for X-ray imaging. Combining 30 nm resolution synchrotron radiation hard X-ray nanocomputed tomography and the X-ray-sensitive Fe@BFK nanoprobe, a 3D localization of HER2 on SK-BR-3 cells was obtained for the first time. HER2 was mainly localized and cluster-distributed on the cell membrane with a heterogeneous pattern. This study provides a novel method for the in situ and nondestructive synchrotron radiation imaging of the desired protein localization in large, thick cells and evaluation of the true cellular distribution of a nanoprobe with high resolution.


Assuntos
Tomografia por Raios X , Humanos , Fluorescência
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