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1.
Eur J Med Chem ; 273: 116503, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38762917

RESUMO

Photodynamic therapy (PDT), an emerging tumor therapeutic strategy has received tremendous attention. Enslaved by the high dependence of oxygen, Type-II photosensitizers (PSs) mediated PDT is restricted by the hypoxic environment of tumors. By transferring electrons to water or other substrates instead of oxygen, Type-I PSs hold the promise of achieving an ideal therapeutic effect under hypoxic conditions. In this study, three twisted-backbone PSs (CBz-TQs-1, CBz-TQs-2 and CBz-TQs-3) are synthesized and studied. Owing to different substituent effects, the ROS generation mechanism transfers from pure Type-II of their prototype PSs (TQs-1, TQs-2 and TQs-3) to mixed Type-I/II of CBz-TQs-1 and CBz-TQs-2 to pure Type-I of CBz-TQs-3. Moreover, CBz-TQs-3 exhibits an ultra-high ROS quantum yield (∼1.0). The in vitro and in vivo PDT effects of water-dissolvable nanoparticles (NPs) of CBz-TQs-3 are investigated. The results show that the phototoxicity of CBz-TQs-3 is not affected by hypoxic environments. In addition, a remarkable tumor ablation can be found after CBz-TQs-3 NPs mediated PDT on Balb/c mice with xenograft tumors. It proves that a twisted backbone strategy is beneficial for designing pure Type-I PSs with high-efficient hypoxic PDT.

2.
Langmuir ; 40(17): 8911-8920, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38624033

RESUMO

Particle rafts are a new kind of soft matter formed by self-organization on the interface, which possesses mechanical properties between fluid and solid, and they have been widely used in many industrial fields. In the present study, the compression experiment of a circular particle raft is first performed, where an SDS (sodium dodecyl sulfate)-coated metal ring is placed around its periphery. When the surfactant diffuses, the particle raft shrinks, and its shrinkage ratio increases with the increase in the surfactant concentration, where the experimental results are consistent with the numerical simulation. Next, the relationship between the initial surface tension difference of SDS and the radius shrinkage of the particle raft is obtained by dimensional analysis. In what follows, the diffusion model is built to quantify the diffusion process of SDS at the liquid-gas interface, and then the analytical concentration solution of the concentration of SDS at the periphery of particle raft is given. The particle raft is viewed as an elastic circular plate under the action of the radial pressure, which originates from the surface tension difference, which has been verified by the experimental result. These explorations cast a new light on how to apply loads to measure mechanical properties of soft matter, which also provide some inspirations on the design of microsensors and microfluidics.

3.
Sci Total Environ ; 927: 171973, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38547995

RESUMO

The aim of this study was to investigate the alleviating effect of selenomethionine (SeMet) on aflatoxin B1 (AFB1)-induced testicular injury in rabbits. Twenty-five 90-d-old rabbits were randomly divided into 5 groups (the control group, the AFB1 group, the 0.2 mg/kg SeMet + AFB1 group, the 0.4 mg/kg SeMet + AFB1 group and the 0.6 mg/kg SeMet + AFB1 group). After 1 d of the experiment, the SeMet-treated groups were fed 0.2 mg/kg SeMet, 0.4 mg/kg SeMet, or 0.6 mg/kg SeMet daily, and the remaining two groups were fed a normal diet for 30 d. On Day 31, all rabbits in the model group and the three treatment groups were fed 0.5 mg/kg AFB1 for 21 d. The levels of testosterone (T), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in rabbit plasma were detected. Rabbit semen was collected, and its quality was evaluated. Pathological changes in rabbit testes were observed by hematoxylin-eosin (HE) staining. The expression of related proteins in testicular tissue was detected by immunohistochemistry, immunofluorescence and western blot (WB) analysis. Enzyme-linked immunosorbent assays (ELISAs) were used to detect oxidative stress-related indices and inflammatory factors in testicular tissue. The results showed that AFB1 can induce oxidative stress and inflammation to activate the p38/MSK/NF-κB signalling pathway, mediate apoptosis, inhibit the proliferation and differentiation of testicular cells, destroy the integrity of the blood-testis barrier (BTB) and the normal structure of the testis, and reduce the content of sex hormones and semen quality. SeMet pretreatment significantly alleviated testicular injury oxidative stress, and the inflammatory response in rabbits. Thus, we demonstrated that SeMet restores AFB1-induced testicular toxicity by inhibiting the p38/MSK/NF-κB signalling pathway. In addition, in this study, 0.4 mg/kg SeMet had the most impactful effect.


Assuntos
Aflatoxina B1 , Selenometionina , Testículo , Animais , Masculino , Coelhos , Aflatoxina B1/toxicidade , Selenometionina/farmacologia , Testículo/efeitos dos fármacos , Testosterona/sangue , Substâncias Protetoras/farmacologia , Doenças Testiculares/prevenção & controle , Doenças Testiculares/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Hormônio Luteinizante/sangue , Apoptose/efeitos dos fármacos
4.
Tob Use Insights ; 17: 1179173X241237216, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455141

RESUMO

Background: Electronic cigarettes (e-cigarettes) remain the most used tobacco product among young people in the United States (US). Given the need for current data on popular e-cigarette products, the current study leverages data from a rapid surveillance survey of young people and examines whether the top e-cigarette brands identified from this source align with US market data. Methodology: Data were obtained from current e-cigarette users (N = 4145) participating in the Truth Continuous Tracker Online (CTO; a cross-sectional tracking survey of 15-24 year-olds sourced from the national Dynata panel) and NielsenIQ retail scanner data, collected in 2022 and aggregated by quarter (Q1, Q2, and Q3). The top 15 e-cigarette brands were determined from respondents' endorsement in the Truth CTO and ranked total sales in NielsenIQ in nominal dollars. Results: Overall, 58% of e-cigarette brands overlapped across the Truth CTO and NielsenIQ data (60% for Q1, 47% for Q2 and 67% for Q3). Pod-based (JUUL; VUSE) and disposable (Hyde; Breeze Smoke) brands appeared as top brands in both datasets. Top brands were fairly consistent within and across quarters; though, more variability was found in the Truth CTO, relative to NielsenIQ. Many top brands were disposable. Conclusions: Results suggest that data from rapid surveillance and retail data can be used complementarily to characterize the popular e-cigarette brands currently on the US market. Many of these popular e-cigarette brands have yet to receive marketing granted orders under the US Food and Drug Administration, suggesting the need to continue monitoring e-cigarette brands among young people.

5.
Nat Commun ; 15(1): 1283, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347023

RESUMO

Additive manufacturing (AM), known as 3D printing, enables rapid fabrication of geometrically complex copper (Cu) components for electrical conduction and heat management applications. However, pure Cu or Cu alloys produced by 3D printing often suffer from either low strength or low conductivity at room and elevated temperatures. Here, we demonstrate a design strategy for 3D printing of high strength, high conductivity Cu by uniformly dispersing a minor portion of lanthanum hexaboride (LaB6) nanoparticles in pure Cu through laser powder bed fusion (L-PBF). We show that trace additions of LaB6 to pure Cu results in an improved L-PBF processability, an enhanced strength, an improved thermal stability, all whilst maintaining a high conductivity. The presented strategy could expand the applicability of 3D printed Cu components to more demanding conditions where high strength, high conductivity and thermal stability are required.

6.
Adv Healthc Mater ; 13(11): e2303856, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38221719

RESUMO

Porphyrin photosensitizers are the classic drugs in clinical photodynamic therapy (PDT), but the hypoxia of tumor environment and the rapid oxygen consumption of PDT severely weaken their therapeutic effect. A recently reported water-dependent reversible photoacidity therapy (W-RPAT) is O2-independence, providing a solution for the treatment of hypoxic tumors. In this work, TPP-O-PEG5, a porphyrin derivative with binary properties of PDT and W-RPAT, is designed and synthesized for the first time. The nanoparticles (NPs) of TPP-O-PEG5 encapsulated with DSPE-mPEG2000, an amphiphilic polymer approved by Food and Drug Administration, can simultaneously produce reactive oxygen species and H+ under irradiation of a 660 nm laser, and revert the H+ back under darkness, presenting strong phototoxicity to multiple tumor cell lines with no obvious difference between the IC50 values tested under normoxic (≈20% O2) and hypoxic (<0.5% O2) conditions. Excitingly, in vivo experiments show that the therapeutic effect of TPP-O-PEG5 NPs on large hypoxic tumors is better than that of NPe6, a clinical porphin PDT drug. This work provides a novel strategy for porphyrin photosensitizers to break through the limitation of hypoxic environment, and significantly improve the phototherapeutic effect on hypoxic tumors.


Assuntos
Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Fotoquimioterapia/métodos , Porfirinas/química , Porfirinas/farmacologia , Humanos , Animais , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Camundongos , Linhagem Celular Tumoral , Água/química , Nanopartículas/química , Espécies Reativas de Oxigênio/metabolismo , Camundongos Endogâmicos BALB C , Hipóxia Tumoral/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Polietilenoglicóis/química , Camundongos Nus
7.
Ecotoxicol Environ Saf ; 269: 115742, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039849

RESUMO

The purpose of this study was to explore the protective effect of SeMet on renal injury induced by AFB1 in rabbits and its molecular mechanism. Forty rabbits of 35 days old were randomly divided into control group, AFB1 group (0.3 mg AFB1/kg b.w), 0.2 mg/kg Se + AFB1 group (0.3 mg AFB1/kg b.w + 0.2 mg SeMet/kg feed) and 0.4 mg/kg Se + AFB1 group (0.3 mg AFB1/kg b.w + 0.4 mg SeMet/kg feed). The SeMet treatment group was fed different doses of SeMet diets every day for 21 days. On the 17-21 day, the AFB1 treatment group, the 0.2 mg/kg Se + AFB1 group and the 0.4 mg/kg Se + AFB1 group were administered 0.3 mg AFB1 /kg b.w by gavage (dissolved in 0.5 ml olive oil) respectively. The results showed that AFB1 poisoning resulted in the changes of renal structure, the increase of renal coefficient and serum biochemical indexes, the ascent of ROS and MDA levels, the descent of antioxidant enzyme activity, and the significant down-regulation of Nrf2, HO-1 and NQO1. Besides, AFB1 poisoning increased the number of renal apoptotic cells, rised the levels of PTEN, Bax, Caspase-3 and Caspase-9, and decreased the levels of PI3K, AKT, p-AKT and Bcl-2. In summary, SeMet was added to alleviate the oxidative stress injury and apoptosis of kidney induced by AFB1, and the effect of 0.2 mg/kg Se + AFB1 is better than 0.4 mg/kg Se + AFB1.


Assuntos
Rim , Estresse Oxidativo , Selenometionina , Animais , Coelhos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Rim/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Selenometionina/farmacologia , Aflatoxina B1/toxicidade , NAD(P)H Desidrogenase (Quinona)/efeitos dos fármacos , NAD(P)H Desidrogenase (Quinona)/metabolismo
8.
Cancer Gene Ther ; 31(2): 217-227, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37990061

RESUMO

TNFRSF19 is a member of the tumor necrosis factor receptor superfamily, and its function exhibits variability among different types of cancers. The influence of TNFRSF19 on triple-negative breast cancer (TNBC) has yet to be definitively established. In this study, bioinformatics analyses revealed that lower TNFRSF19 was associated with the poorer prognosis, higher lymph node metastasis and lower immune infiltration. Subsequently, data obtained from the TCGA database and collection of tissue samples revealed that the mRNA and protein expression levels of TNFRSF19 were observed to be significantly reduced in TNBC tissue compared to normal tissue. Additionally, the results of in vitro experiments have demonstrated that TNFRSF19 possessed the ability to inhibit the proliferation, migration and invasive capabilities of TNBC cells. In vivo trials elucidated that TNFRSF19 could suppress tumor xenografts growth. Mechanistically, TNFRSF19 initiated caspase-independent cell death and induced paraptosis. Moreover, rescue assays demonstrated that TNFRSF19 induced-paraptosis was facilitated by MAPK pathway-mediated endoplasmic reticulum (ER) stress. In conclusion, our findings demonstrated that the upregulation of TNFRSF19 functioned as a tumor suppressor in TNBC by stimulating paraptosis through the activation of the MAPK pathway-mediated ER stress, highlighting its potential to be a new therapeutic target for TNBC.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/metabolismo , Paraptose , Linhagem Celular Tumoral , Estresse do Retículo Endoplasmático , Receptores do Fator de Necrose Tumoral/metabolismo , Proliferação de Células/genética
9.
Eur J Med Chem ; 265: 116059, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38134744

RESUMO

Most photosensitizers (PSs) for photodynamic therapy (PDT) can generate singlet oxygen through transferring energy with oxygen, called Type-II PSs. However, the microenvironment of solid tumor is usually anoxic. Type-I PSs can generate reactive oxygen species (ROS) through transferring electron to substrate, showing more efficient in PDT. But pure Type-I PSs are very rare. The relationship between PSs' chemical structure and Type-I mechanism has not been explicitly stated. In this study, two thiadiazolo [3,4-g]quinoxaline (TQ) PSs (PsCBz-1 and PsCBz-2) are synthesized through introducing carbazole groups to the 4,9-position of TQ backbone. Comparing with their prototype PS, 4,9-dibrominated TQ (TQs-4), the introduction of carbazole groups reverses the reaction mechanism of PSs from pure Type-II to pure Type-I. Excitingly, the water-dispersible nanoparticles (NPs) of PsCBz-1 can achieve strong phototoxicity in vitro under both normoxia and hypoxia through Type-I mechanism. In addition, PsCBz-1 NPs also exhibits remarkable PDT antitumor effect in vivo. This study provides a feasible design strategy for pure Type-I PSs.


Assuntos
Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/química , Quinoxalinas/farmacologia , Quinoxalinas/uso terapêutico , Neoplasias/tratamento farmacológico , Espécies Reativas de Oxigênio , Carbazóis , Microambiente Tumoral
10.
Angew Chem Int Ed Engl ; 63(7): e202317987, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38152839

RESUMO

Platinum metal (PtM, M=Ni, Fe, Co) alloys catalysts show high oxygen reduction reaction (ORR) activity due to their well-known strain and ligand effects. However, these PtM alloys usually suffer from a deficient ORR durability in acidic environment as the alloyed metal is prone to be dissolved due to its high electronegativity. Herein, we report a new class of PtMn alloy nanodendrite catalyst with low-electronegativity Mn-contraction for boosting the oxygen reduction durability of fuel cells. The moderate strain in PtMn, induced by Mn contraction, yields optimal oxygen reduction activity at 0.53 A mg-1 at 0.9 V versus reversible hydrogen electrode (RHE). Most importantly, we show that relative to well-known high-electronegativity Ni-based Pt alloy counterpart, the PtMn nanodendrite catalyst experiences less transition metals' dissolution in acidic solution and achieves an outstanding mass activity retention of 96 % after 10,000 degradation cycles. Density functional theory calculation reveals that PtMn alloys are thermodynamically more stable than PtNi alloys in terms of formation enthalpy and cohesive energy. The PtMn nanodendrite-based membrane electrode assembly delivers an outstanding peak power density of 1.36 W cm-2 at a low Pt loading and high-performance retention over 50 h operations at 0.6 V in H2 -O2 hydrogen fuel cells.

11.
J Phys Condens Matter ; 36(13)2023 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-38096581

RESUMO

By combining first-principles density-functional calculations and thermodynamics, we investigated the thermodynamic stability and mechanical properties of 15 quaternary high-entropy metal disilicides composed of silicon and four of the six refractory transition metals Ti, Zr, Hf, V, Nb, and Ta. We constructed a three-dimensional diagram specified by two thermodynamic parameters (the mixing enthalpy and the ratio of the entropy term in the Gibbs free energy to enthalpy) and a structural parameter (the lattice size difference). The obtained diagram allows us to predict that, except for TiZrHfVSi8, the formation of all other fourteen single-phase metal disilicides is thermodynamically favorable. Our calculations show that, for the formation of each of the 14 metal disilicides, the driving force suppresses the resistance at temperatures well below the melting point, suggesting that it is feasible to synthesize these high-entropy materials. One of these (TiHfNbTaSi8) has already been experimentally realized. Furthermore, the values of the mechanical parameters and melting points of the predicted fourteen quaternary high-entropy metal disilicides are all greater than the corresponding average values of the four single-metal disilicides.

12.
Front Plant Sci ; 14: 1260625, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38126009

RESUMO

In the production of edible fungi, the use of degraded strains in cultivation incurs significant economic losses. Based on micro-hyperspectral imaging and machine learning, this study proposes an early, nondestructive method for detecting different degradation degrees of Pleurotus geesteranus strains. In this study, an undegraded strain and three different degradation-level strains were used. During the mycelium growth, 600 micro-hyperspectral images were obtained. Based on the average transmittance spectra of the region of interest (ROI) in the range of 400-1000 nm and images at feature bands, feature spectra and images were extracted using the successive projections algorithm (SPA) and the deep residual network (ResNet50), respectively. Different feature input combinations were utilized to establish support vector machine (SVM) classification models. Based on the results, the spectra-input-based model performed better than the image-input-based model, and feature extraction improved the classification results for both models. The feature-fusion-based SPA+ResNet50-SVM model was the best; the accuracy rate of the test set was up to 90.8%, which was better than the accuracy rates of SPA-SVM (83.3%) and ResNet50-SVM (80.8%). This study proposes a nondestructive method to detect the degradation of Pleurotus geesteranus strains, which could further inspire new methods for the phenotypic identification of edible fungi.

13.
NPJ Breast Cancer ; 9(1): 93, 2023 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-37957150

RESUMO

Microcalcification (MC) is a valuable diagnostic indicator of breast cancer, and it is reported to be associated with increased tumor aggressiveness and poor prognosis. Nevertheless, the exact potential molecular mechanism is not completely understood. Here, we find that the mineralized invasive breast cancer (IBC) cells not only increased their proliferation and migration, but also showed the characteristic of doxorubicin resistance. The PI3K/AKT signaling pathway is associated with the generation of calcification in IBC, and it activates the transcription and translation of its downstream hypoxia-inducible factor 1α (HIF1α). Knockdown of HIF1α protein significantly downregulated cell proliferation and migration while calcification persists. Meanwhile, calcified breast cancer cells restored sensitivity to doxorubicin because of suppressed HIF1α expression. In addition, we provide initial data on the underlying value of HIF1α as a biomarker of doxorubicin resistance. These findings provide a new direction for exploring microcalcifications in IBC.

14.
Org Lett ; 25(40): 7428-7433, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37791679

RESUMO

A B(C6F5)3-catalyzed controllable inter/intra-/intermolecular Si-C bond formation process has been developed from trihydrosilane and dienamide with alkenes, anilines, or aryl iodides. A variety of 1,4-azasilinanes have been generated with diverse exo-cyclic heteroleptic disubstitutions on silicon, thereby expanding the range of silaazacyclic rings available for the discovery of silicon-containing drugs.

15.
Cell Signal ; 112: 110918, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37827342

RESUMO

BACKGROUND: PROS1 is an encoding gene that can generate protein S. This protein is a glycoprotein found in plasma that conducts physiological functions with vitamin K. However, the impact of its expression remains absent in the progression and prognosis of breast cancer (BC). METHODS: In this study, we comprehensively explored the expression of PROS1 in BC and its relationship with BC patient survival, prognosis, and other clinicopathological features. We investigated how PROS1 influenced the malignant biological behavior of BC cells. A series of enrichment analyses were conducted, and the immune landscape was explored in BC affected by PROS1. We also determined correlations between PROS1 and common drug sensitivities used for BC treatments. RESULTS: PROS1 had low expression in BC, which tended to result in poor survival of BC patients. Overexpressed PROS1 inhibited the migration and invasion of BC cells as well as the epithelial-mesenchymal transition process by downregulating SNAIL. Functional enrichment analyses revealed that PROS1 was more active in extracellular matrix (ECM) organization and structural constituent, ECM-receptor interaction, and other pathways with its related genes. PROS1 was also found to affect immune activity, including various immune cells infiltrating BC. BC patients with high PROS1 expression tended to have lower IC50 values of three common medications and obtained better efficacy. CONCLUSIONS: PROS1 can become a promising prognostic factor and a possible therapeutic target in BC patients and suppress BC cell metastatic potential. In addition, PROS1 is a crucial factor in immune infiltration in BC.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Prognóstico , Neoplasias da Mama/genética , Transição Epitelial-Mesenquimal/genética , Biologia Computacional , Biomarcadores , Proteína S
16.
Prev Med Rep ; 36: 102416, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37753384

RESUMO

Purpose: Temporal patterns of daily tobacco product use among ever users from the Truth Longitudinal Cohort (TLC) between 2018 and 2019 were explored. Methods: The sample (N = 5274) includes individuals (15-36 years), residing in the United States, who had ever used any tobacco product at Wave 7 (February - May 2018) and provided tobacco use information at Wave 9 (September - December 2019). Results: There was a nonsignificant 1.1 percentage point increase in daily tobacco use (on at least 25 of the past 30 days), from 14.6% (95% CI: 12.8, 16.6) to 15.7% (95% CI: 13.8, 17.7). Tobacco product use remained stable over time, as 65.3% (95% CI: 56.4, 73.3) of daily cigarette smokers, 57.0% (95% CI: 43.6, 69.4) of daily e-cigarette vapers, and 8.5% (95% CI: 2.0, 29.3) of daily dual users stayed with their primary tobacco product. There was also some evidence of switching, as 7.5% (95% CI: 3.7, 14.8) of daily cigarette smokers became daily e-cigarette vapers and 2.3% (95% CI: 0.7, 6.8) of daily e-cigarette vapers became daily cigarette smokers. Discussion: Although most daily tobacco users were likely to continue using their primary product, some daily users transitioned to daily use of other products - suggesting that policies and public education focused on reducing overall nicotine use are essential for addressing the nicotine epidemic among young people.

17.
ISA Trans ; 142: 478-491, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37659869

RESUMO

This paper is concerned with the fault detection problem for the rotary steerable drilling tool system under unknown vibrations and limited computational resources. Firstly, the drilling tool system can be modeled by a nonlinear stochastic system with unknown time-varying noise covariances. Then, the dynamic event-triggered mechanism is introduced to save computational resources, and the caused transmission error is completely decoupled by nonuniform sampling. Subsequently, a novel unscented Kalman filter is proposed by combining the expectation maximization method to estimate states when noise covariances are unknown. A residual and an evaluation function are constructed to detect faults. Finally, a numerical simulation and an experiment on a drilling tool prototype validate the superior performance of the proposed fault detection scheme, which has lower missed alarm rates and consumes less time than existing methods.

18.
BMC Cancer ; 23(1): 851, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37697245

RESUMO

BACKGROUND: A number of human diseases have been associated with Centromere protein N (CENPN), but its role in breast cancer is unclear. METHODS: A pan-cancer database of Genotype Tissue Expression (GTEx) and the Cancer Genome Atlas (TCGA) were used to examine the expression of CENPN. Using TCGA clinical survival data and breast cancer specimens from our center for validation, the relationship between CENPN expression, breast cancer prognosis, and clinicopathological characteristics of patients was examined. Bioinformatics was utilized to conduct an enrichment study of CENPN. Additionally, the potential of CENPN as a predictive biomarker for immunotherapy success was confirmed by analyzing the co-expression of CENPN with immune-checkpoint related genes, reviewing the TCGA database, and evaluating the correlation between CENPN expression and immune cell infiltration. Using the CCK8 test and colony formation assay, CENPN was evaluated for its ability to inhibit breast cancer cell proliferation. Transwell assays and scratch tests were used to assess the impact of CENPN on breast cancer cell migration. RESULTS: CENPN is found in a wide range of tumors, including breast cancer. Additional investigation revealed that CENPN was co-expressed with the majority of immune checkpoint-related genes, had the potential to serve as a predictive biomarker for immunotherapy effectiveness, and that high CENPN expression was linked to high Tregs and low CD8 + T cells and NK cells. Breast cancer cells' malignant characteristics, such as migration and cell proliferation, were inhibited by CENPN knockdown. CONCLUSIONS: According to our findings, CENPN may be an oncogene in breast cancer, as well as a new therapeutic target for immune checkpoint inhibitors.


Assuntos
Neoplasias da Mama , Proteínas Cromossômicas não Histona , Feminino , Humanos , Neoplasias da Mama/genética , Proliferação de Células/genética , Biologia Computacional , Oncogenes
19.
Front Cell Dev Biol ; 11: 1166916, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37152280

RESUMO

Malignant melanoma (MM) is the most metastatic and aggressive form of skin cancer, and carries a high risk of death. Immune-checkpoint inhibitor therapy and molecular-targeted therapy can prolong the survival of patients with advanced MM significantly. However, the low response rate and inevitable drug resistance prevent further improvements in efficacy, which is closely related to the tumor microenvironment (TME). The TME refers to the tumor stroma, including fibroblasts, keratinocytes, immune cells, soluble molecules, and extracellular matrix (ECM). The dynamic interaction between the TME and tumor cells is very important for the growth, local invasion, and metastatic spread of tumor cells. A patient-derived organoid (PDO) model involves isolation of tumor tissue from patients with MM and culturing it in vitro in a three-dimensional pattern. Compared with traditional cultivation methods, the PDO model preserves the heterogeneity of the tissue structure of MM and demonstrates the interaction between MM cells and the TME. It can reproduce the characteristics of proliferation, migration, and invasion of MM cells, and better simulate the structural function of MM in vivo. This review explores the role of each TME component in development of the PDO model. This review will provide a reference for research on the drug screening and targeted treatment using PDOs, particularly for the immunotherapy of MM.

20.
Bioinspir Biomim ; 18(4)2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37187174

RESUMO

With the rapid development of origami technology, worm-inspired origami robots have attracted tremendous interest owing to their colourful locomotion behaviours, such as creeping, rolling, climbing and obstacle crossing. In the present study, we aim to engineer a worm-inspired robot based on knitting process with paper, which could realize complicated functions associated large deformation and exquisite locomotion patterns. At first we fabricate the backbone of the robot by using the paper-knitting technique. The experiment shows that the backbone of the robot can endure significant deformation during the tension, compression and bending process, and this feature ensures it can achieve the desired targets of motion. Next, the magnetic forces and torques under the actuation of permanent magnets are analysed, which are just the driving forces of the robot. We then consider three formats of motion on the robot, i.e. the inchworm motion, the Omega motion, and the hybrid motion. Typical examples for the robot fulfil desired tasks are given, including sweeping obstacles, climbing the wall and delivering cargoes. Detailed theoretical analyses and numerical simulations are performed to illustrate these experimental phenomena. The results show that the developed origami robot is equipped with such characteristics as lightweight and great flexibility, which is sufficiently robust in various environments. These promising performances shed new light on design and fabrication of bio-inspired robots with good intelligence.


Assuntos
Robótica , Locomoção , Imãs , Movimento (Física) , Campos Magnéticos
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