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1.
Parasit Vectors ; 17(1): 214, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730303

RESUMO

BACKGROUND: Triatomines (kissing bugs) are natural vectors of trypanosomes, which are single-celled parasitic protozoans, such as Trypanosoma cruzi, T. conorhini and T. rangeli. The understanding of the transmission cycle of T. conorhini and Triatoma rubrofasciata in China is not fully known. METHODS: The parasites in the faeces and intestinal contents of the Tr. rubrofasciata were collected, and morphology indices were measured under a microscope to determine the species. DNA was extracted from the samples, and fragments of 18S rRNA, heat shock protein 70 (HSP70) and glycosomal glyceraldehyde-3-phosphate dehydrogenase (gGAPDH) were amplified and sequenced. The obtained sequences were then identified using the BLAST search engine, followed by several phylogenetic analyses. Finally, laboratory infections were conducted to test whether Tr. rubrofasciata transmit the parasite to rats (or mice) through bites. Moreover, 135 Tr. rubrofasciata samples were collected from the Guangxi region and were used in assays to investigate the prevalence of trypanosome infection. RESULTS: Trypanosoma sp. were found in the faeces and intestinal contents of Tr. rubrofasciata, which were collected in the Guangxi region of southern China and mostly exhibited characteristics typical of epimastigotes, such as the presence of a nucleus, a free flagellum and a kinetoplast. The body length ranged from 6.3 to 33.9 µm, the flagellum length ranged from 8.7 to 29.8 µm, the nucleus index was 0.6 and the kinetoplast length was -4.6. BLAST analysis revealed that the 18S rRNA, HSP70 and gGAPDH sequences of Trypanosoma sp. exhibited the highest degree of similarity with those of T. conorhini (99.7%, 99.0% and 99.0%, respectively) and formed a well-supported clade close to T. conorhini and T. vespertilionis but were distinct from those of T. rangeli and T. cruzi. Laboratory experiments revealed that both rats and mice developed low parasitaemia after inoculation with Trypanosoma sp. and laboratory-fed Tr. rubrofasciata became infected after feeding on trypanosome-positive rats and mice. However, the infected Tr. rubrofasciata did not transmit Trypanosoma sp. to their offspring. Moreover, our investigation revealed a high prevalence of Trypanosoma sp. infection in Tr. rubrofasciata, with up to 36.3% of specimens tested in the field being infected. CONCLUSIONS: Our study is the first to provide a solid record of T. conorhini from Tr. rubrofasciata in China with morphological and molecular evidence. This Chinese T. conorhini is unlikely to have spread through transovarial transmission in Tr. rubrofasciata, but instead, it is more likely that the parasite is transmitted between Tr. rubrofasciata and mice (or rats). However, there was a high prevalence of T. conorhini in the Tr. rubrofasciata from our collection sites and numerous human cases of Tr. rubrofasciata bites were recorded. Moreover, whether these T. conorhini strains are pathogenic to humans has not been investigated.


Assuntos
Insetos Vetores , Filogenia , RNA Ribossômico 18S , Triatoma , Trypanosoma , Animais , China/epidemiologia , Ratos , Camundongos , Trypanosoma/genética , Trypanosoma/isolamento & purificação , Trypanosoma/classificação , Triatoma/parasitologia , RNA Ribossômico 18S/genética , Insetos Vetores/parasitologia , Tripanossomíase/parasitologia , Tripanossomíase/transmissão , Tripanossomíase/veterinária , Tripanossomíase/epidemiologia , Fezes/parasitologia , Proteínas de Choque Térmico HSP70/genética , DNA de Protozoário/genética , Feminino , Masculino
3.
Artigo em Inglês | MEDLINE | ID: mdl-38748448

RESUMO

The development of optical humidity detection has been of considerable interest in highly integrated wearable electronics and packaged equipment. However, improving their capacities for color recognition at ultralow humidity and response-recovery rate remains a significant challenge. Herein, we propose a type of hybrid water-harvesting channel to construct brand-new passive fluorescence humidity sensors (PFHSs). Specifically, the hybrid water-harvesting channels involve porous metal-organic frameworks and a hydrophilic poly(acrylic acid) network that can capture water vapors from the ambient environment even at ultralow humidity, into which polar-responsive aggregation-induced emission molecules are doped to impart humidity-sensitive luminescence colors. As a result, the PFHSs exhibit clearly defined fluorescence signals within 0-98% RH coupling with desirable performances such as a fast response rate, precise quantitative feedback, and durable reversibility. Given the flexible processability of this system, we further upgrade the porous structure via electrostatic spinning to furnish a kind of Nano-PFHSs, demonstrating an impressive response time (<100 ms). Finally, we validate the promising applications of these sensors in electronic humidity monitoring and successfully fabricate a portable and rapid humidity indicator card.

4.
Sci Rep ; 14(1): 10899, 2024 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740854

RESUMO

In order to obtain the best mass spectrometry identification results for using the most appropriate methods in clinical practice, we explore the optimal pretreatment methods for different species and morphologies of filamentous fungi. 98 fungal strains were treated with formic acid sandwich method, dispersion method, extraction method, and other methods using a medium element mass spectrometer (EXS3000) as a platform. Each strain had three targets, and the identification rates and confidence differences under different pre-treatment methods were compared to evaluate the identification effects of these methods. The mass spectrometry identification rates of 98 filamentous fungi obtained after pre-treatment with formic acid sandwich method, dispersion method, and extraction method were 85.71%, 82.65%, and 75.51%, respectively. The identification rate of the formic acid sandwich method was significantly higher than the other two methods (P < 0 005) has the best identification ability and the obtained confidence is also higher than the other two methods. The use of formic acid sandwich method for mass spectrometry identification of filamentous fungi can achieve ideal identification results, which is suitable for mass spectrometry identification of filamentous fungi in conventional laboratories.


Assuntos
Fungos , Espectrometria de Massas , Fungos/isolamento & purificação , Fungos/classificação , Espectrometria de Massas/métodos , Formiatos/química , Formiatos/análise , Micoses/microbiologia , Micoses/diagnóstico , Humanos
5.
Physiol Meas ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722570

RESUMO

OBJECTIVE: Impedance pneumography (IP) has provided static assessments of subjects' breathing patterns in previous studies. Evaluating the feasibility and limitation of ambulatory IP based respiratory monitoring needs further investigation on clinically relevant exercise designs. The aim of this study was to evaluate the capacity of an advanced IP in ambulatory respiratory monitoring, and its predictive value in independent ventilatory capacity quantification during cardiopulmonary exercise testing (CPET). Approach: 35 volunteers were examined with the same calibration methodology and CPET exercise protocol comprising phases of rest, unloaded, incremental load, maximum load, recovery and further-recovery. In 3 or 4 deep breaths of calibration stage, thoracic impedance and criterion spirometric volume were simultaneously recorded to produce phase-specific prior calibration coefficients (CCs). The IP measurement during exercise protocol was converted by prior CCs to volume estimation curve and thus calculate minute ventilation (VE) independent from the spirometry approach. Main results: Across all measurements, the relative error of IP-derived VE (VER) and flowrate-derived VE (VEf) was less than 13.8%. In Bland-Altman plots, the aggregate VE estimation bias was statistically insignificant for all 3 phases with pedaling exercise and the discrepancy between VERand VEffell within the 95% limits of agreement (95% LoA) for 34 or all subjects in each of all CPET phases. Significance: This work reinforces the independent use of IP as an accurate and robust alternative to flowmeter for applications in cycle ergometry CPET, which could significantly encourage the clinical use of IP and improve the convenience and comfort of CPET.

6.
Angew Chem Int Ed Engl ; : e202403391, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717757

RESUMO

Room temperature phosphorescence (RTP) materials have garnered significant attention owing to its distinctive optical characteristics and broad range of potential applications. However, the challenge remains in producing RTP materials with more simplicity, versatility, and practicality on a large scale, particularly in achieving chiral signals within a single system. Herein, we show that a straightforward and effective combination of wet spinning and twisting technique enables continuously fabricating RTP fibers with twisting-induced helical chirality. By leveraging the hydrogen bonding interactions between polyvinyl alcohol (PVA) and quinoline derivatives, along with the rigid microenvironment provided by PVA chains, typically, Q-NH2@PVA fiber demonstrates outstanding phosphorescent characteristics with RTP lifetime of 1.08 s and phosphorescence quantum yield of 24.6%, and the improved tensile strength being 1.7 times than pure PVA fiber (172 ± 5.82 vs 100 ± 5.65 MPa). Impressively, the transformation from RTP to circularly polarized room temperature phosphorescence (CP-RTP) is readily achieved by imparting left- or right-hand helical structure through simply twisting, enabling large-scale production of chiral Q-NH2@PVA fiber with dissymmetry factor of 10-2. Besides, an array of displays and encryption patterns are crafted by weaving or seaming to exemplify the promising applications of these PVA-based fibers with outstanding adaptivity in cutting-edge anti-counterfeiting technology.

8.
Bioact Mater ; 37: 331-347, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38694762

RESUMO

Engineered bacteria have shown great potential in cancer immunotherapy by dynamically releasing therapeutic payloads and inducing sustained antitumor immune response with the crosstalk of immune cells. In previous studies, FOLactis was designed, which could secret an encoded fusion protein of Fms-related tyrosine kinase 3 ligand and co-stimulator OX40 ligand, leading to remarkable tumor suppression and exerting an abscopal effect by intratumoral injection. However, it is difficult for intratumoral administration of FOLactis in solid tumors with firm texture or high internal pressure. For patients without lesions such as abdominal metastatic tumors and orthotopic gastric tumors, intratumoral injection is not feasible and peritumoral maybe a better choice. Herein, an engineered bacteria delivery system is constructed based on in situ temperature-sensitive poloxamer 407 hydrogels. Peritumoral injection of FOLactis/P407 results in a 5-fold increase in the proportion of activated DC cells and a more than 2-fold increase in the proportion of effective memory T cells (TEM), playing the role of artificial lymph island. Besides, administration of FOLactis/P407 significantly inhibits the growth of abdominal metastatic tumors and orthotopic gastric tumors, resulting in an extended survival time. Therefore, these findings demonstrate the delivery approach of engineered bacteria based on in situ hydrogel will promote the efficacy and universality of therapeutics.

9.
Front Public Health ; 12: 1348234, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590814

RESUMO

China is actively encouraging households to replace traditional solid fuels with clean energy. Based on the Chinese Families Panel Survey (CFPS) data, this paper uses propensity scores matching with the difference-in-differences model to examine the impact of clean energy in the household sector on residents' health status, and whether such an energy transition promotes health equity by favoring relatively disadvantaged social groups. The results show that: (1) The use of cleaner cooking fuels can significantly improve residents' health status; (2) The older adult and women have higher health returns from the clean energy transition, demonstrating that, from the perspective of age and gender, the energy transition contributes to the promotion of health equity; (3) The clean energy transition has a lower or insignificant health impact on residents who cannot easily obtain clean energy or replace non-clean energy at an affordable price. Most of these individuals live in low-income, energy-poor, or rural households. Thus, the energy transition exacerbates health inequalities. This paper suggests that to reduce the cost of using clean energy and help address key issues in health inequality, Chinese government efforts should focus on improving the affordability, accessibility, and reliability of clean energy.


Assuntos
Poluição do Ar em Ambientes Fechados , Humanos , Feminino , Idoso , Poluição do Ar em Ambientes Fechados/análise , Disparidades nos Níveis de Saúde , Reprodutibilidade dos Testes , China , Desigualdades de Saúde
10.
Ecol Evol ; 14(4): e11278, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628918

RESUMO

Although several phylogeographic studies of Asian snakes have been conducted, most have focused on pitvipers, with non-venomous snakes, such as colubrids or natricids, remaining poorly studied. The Chinese keelback water snake (Trimerodytes percarinatus Boulenger) is a widespread, semiaquatic, non-venomous species occurring in China and southeastern Asia. Based on mitochondrial DNA (mtDNA) and single nucleotide polymorphism (SNP) data, we explored the population genetic structure, genetic diversity, and evolutionary history of this species. MtDNA-based phylogenetic analysis showed that T. percarinatus was composed of five highly supported and geographically structured lineages. SNP-based phylogenetic analysis, principal component analysis, and population structure analysis consistently revealed four distinct, geographically non-overlapping lineages, which was different from the mtDNA-based analysis in topology. Estimation of divergence dates and ancestral area of origin suggest that T. percarinatus originated ~12.68 million years ago (95% highest posterior density: 10.36-15.96 Mya) in a region covering southwestern China and Vietnam. Intraspecific divergence may have been triggered by the Qinghai-Xizang Plateau uplift. Population demographics and ecological niche modeling indicated that the effective population size fluctuated during 0.5 Mya and 0.002 Mya. Based on the data collected here, we also comment on the intraspecific taxonomy of T. percarinatus and question the validity of the subspecies T. p. suriki.

11.
Adv Sci (Weinh) ; : e2401046, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38666450

RESUMO

Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterized by excessive proliferation of rheumatoid arthritis synovial fibroblasts (RASFs) and accumulation of inflammatory cytokines. Exploring the suppression of RASFs and modulation of the RA microenvironment is considered a comprehensive strategy for RA. In this work, specifically activated nanoagents (MAHI NGs) based on the hypoxic and weakly acidic RA microenvironment are developed to achieve a second near-infrared fluorescence (NIR-II FL)/photoacoustic (PA) dual-model imaging-guided multi-treatment. Due to optimal size, the MAHI NGs passively accumulate in the diseased joint region and undergo rapid responsive degradation, precisely releasing functionalized components: endogenous melanin-nanoparticles (MNPs), hydrogen gas (H2), and indocyanine green (ICG). The released MNPs play a crucial role in ablating RASFs within the RA microenvironment through photothermal therapy (PTT) guided by accurate PA imaging. However, the regional hyperthermia generated by PTT may exacerbate reactive oxygen species (ROS) production and inflammatory response following cell lysis. Remarkably, under the acidic microenvironment, the controlled release of H2 exhibits precise synergistic antioxidant and anti-inflammatory effects with MNPs. Moreover, the ICG, the second near-infrared dye currently approved for clinical use, possesses excellent NIR-II FL imaging properties that facilitate the diagnosis of deep tissue diseases and provide the right time-point for PTT.

12.
Mater Today Bio ; 26: 101054, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38633865

RESUMO

The hypoxic tumor microenvironment (TME) of osteosarcoma (OS) is the Achilles' heel of oxygen-dependent photodynamic therapy (PDT), and tremendous challenges are confronted to reverse the hypoxia. Herein, we proposed a "reducing expenditure of O2 and broadening sources" dual-strategy and constructed ultrasmall IrO2@BSA-ATO nanogenerators (NGs) for decreasing the O2-consumption and elevating the O2-supply simultaneously. As O2 NGs, the intrinsic catalase (CAT) activity could precisely decompose the overexpressed H2O2 to produce O2 in situ, enabling exogenous O2 infusion. Moreover, the cell respiration inhibitor atovaquone (ATO) would be at the tumor sites, effectively inhibiting cell respiration and elevating oxygen content for endogenous O2 conservation. As a result, IrO2@BSA-ATO NGs systematically increase tumor oxygenation in dual ways and significantly enhance the antitumor efficacy of PDT. Moreover, the extraordinary photothermal conversion efficiency allows the implementation of precise photothermal therapy (PTT) under photoacoustic guidance. Upon a single laser irradiation, this synergistic PDT, PTT, and the following immunosuppression regulation performance of IrO2@BSA-ATO NGs achieved a superior tumor cooperative eradicating capability both in vitro and in vivo. Taken together, this study proposes an innovative dual-strategy to address the serious hypoxia problem, and this microenvironment-regulable IrO2@BSA-ATO NGs as a multifunctional theranostics platform shows great potential for OS therapy.

13.
Pattern Recognit ; 1522024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38645435

RESUMO

Deep learning models for medical image segmentation are usually trained with voxel-wise losses, e.g., cross-entropy loss, focusing on unary supervision without considering inter-voxel relationships. This oversight potentially leads to semantically inconsistent predictions. Here, we propose a contextual similarity loss (CSL) and a structural similarity loss (SSL) to explicitly and efficiently incorporate inter-voxel relationships for improved performance. The CSL promotes consistency in predicted object categories for each image sub-region compared to ground truth. The SSL enforces compatibility between the predictions of voxel pairs by computing pair-wise distances between them, ensuring that voxels of the same class are close together whereas those from different classes are separated by a wide margin in the distribution space. The effectiveness of the CSL and SSL is evaluated using a clinical cone-beam computed tomography (CBCT) dataset of patients with various craniomaxillofacial (CMF) deformities and a public pancreas dataset. Experimental results show that the CSL and SSL outperform state-of-the-art regional loss functions in preserving segmentation semantics.

14.
J Transl Med ; 22(1): 341, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594751

RESUMO

BACKGROUND: Chemoimmunotherapy has shown promising advantages of eliciting immunogenic cell death and activating anti-tumor immune responses. However, the systemic toxicity of chemotherapy and tumor immunosuppressive microenvironment limit the clinical application. METHODS: Here, an injectable sodium alginate hydrogel (ALG) loaded with nanoparticle albumin-bound-paclitaxel (Nab-PTX) and an immunostimulating agent R837 was developed for local administration. Two murine hepatocellular carcinoma and breast cancer models were established. The tumor-bearing mice received the peritumoral injection of R837/Nab-PTX/ALG once a week for two weeks. The antitumor efficacy, the immune response, and the tumor microenvironment were investigated. RESULTS: This chemoimmunotherapy hydrogel with sustained-release character was proven to have significant effects on killing tumor cells and inhibiting tumor growth. Peritumoral injection of our hydrogel caused little harm to normal organs and triggered a potent antitumor immune response against both hepatocellular carcinoma and breast cancer. In the tumor microenvironment, enhanced immunogenic cell death induced by the combination of Nab-PTX and R837 resulted in 3.30-fold infiltration of effector memory T cells and upregulation of 20 biological processes related to immune responses. CONCLUSIONS: Our strategy provides a novel insight into the combination of chemotherapy and immunotherapy and has the potential for clinical translation.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Camundongos , Animais , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Imiquimode/farmacologia , Imiquimode/uso terapêutico , Morte Celular Imunogênica , Linhagem Celular Tumoral , Neoplasias Hepáticas/tratamento farmacológico , Imunoterapia/métodos , Imunidade , Microambiente Tumoral
15.
Nat Commun ; 15(1): 3035, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38600088

RESUMO

People living with HIV (PLWH) experience increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors associated with this vulnerability remain uncertain. In the general population, alterations in the N-glycans on IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG N-glycans in cross-sectional and longitudinal samples from 1214 women and men, living with and without HIV. PLWH exhibit an accelerated accumulation of pro-aging-associated glycan alterations and heightened expression of senescence-associated glycan-degrading enzymes compared to controls. These alterations correlate with elevated markers of inflammation and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit a reduced ability to elicit anti-HIV Fc-mediated immune activities. These findings hold potential for the development of biomarkers and tools to identify and prevent premature aging and comorbidities in PLWH.


Assuntos
Senilidade Prematura , Infecções por HIV , Masculino , Humanos , Feminino , Imunoglobulina G , Estudos Transversais , Envelhecimento , Inflamação/complicações , Polissacarídeos
16.
Heliyon ; 10(7): e28867, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38601545

RESUMO

Thyroid storm (TS) leading to acute liver failure is rare but fatal in clinical practice and hepatic failure can remarkably limit medication options for TS. We successfully cured a patient with TS complicated with acute hepatic failure using therapeutic plasma exchange (TPE) and a double plasma molecular absorption system (DPMAS) and summarized the case characteristics of 10 similar critical patients reported worldwide. We recommend that patients with TS complicated with liver failure disuse propylthiouracil or methimazole. TPE should be utilized to rapidly decrease thyroid hormone levels, and DPMAS should be considered for supportive treatment in the presence of hepatic encephalopathy or dramatic bilirubin elevations.

17.
J Hazard Mater ; 470: 134160, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38574665

RESUMO

OBJECTIVE: To investigate the effects of polycyclic aromatic hydrocarbons(PAHs) on puberty in boys. METHODS: 695 subjects were selected from four primary schools in Chongqing, China. 675 urine samples from these boys were collected four PAH metabolites: 1-hydroxypyrene, 2-hydroxynaphthoic, 2-hydroxyfluorene, and 9-hydroxyphenanthrene. Pubertal development of 695 boys was assessed at follow-up visits starting in December 2015 and occurring every six months thereafter until now, data used in this article ending in June 2021. A total of 12 follow-up visits were performed. Cox proportional hazards regression models were used to analyze the relationship between PAH metabolite concentrations and indicators of pubertal timing. RESULTS: The mean age at puberty onset of testicular volume, facial hair, pubic hair, first ejaculation, and axillary hair in boys was 11.66, 12.43, 12.51, 12.72 and 13.70 years, respectively. Cox proportional hazards regression models showed that boys with moderate level of 1-OHPyr exposure was associated with earlier testicular development (hazard ratio [HR] = 1.276, 95% confidence interval [CI]: 1.006-1.619), with moderate level of 2-OHNap were at higher risk of early testicular development (HR = 1.273, 95% CI: 1.002-1.617) and early axillary hair development (HR = 1.355, 95% CI: 1.040-1.764), with moderate level of 2-OHFlu was associated with earlier pubic hair development (HR = 1.256, 95% CI: 1.001-1.577), with high level of 9-OHPhe were at higher risk of early fisrt ejaculation (HR = 1.333, 95% CI: 1.005-1.767) and early facial hair development (HR = 1.393, 95% CI: 1.059-1.831). CONCLUSION: Prepubertal exposure to PAHs may be associated with earlier pubertal development in boys.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Puberdade , Humanos , Masculino , Hidrocarbonetos Policíclicos Aromáticos/urina , Hidrocarbonetos Policíclicos Aromáticos/toxicidade , Criança , Adolescente , Puberdade/efeitos dos fármacos , Estudos Longitudinais , China , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Poluentes Ambientais/toxicidade , Poluentes Ambientais/urina , Maturidade Sexual/efeitos dos fármacos , Testículo/efeitos dos fármacos , Modelos de Riscos Proporcionais
18.
Materials (Basel) ; 17(7)2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-38611994

RESUMO

The impacts of various aggregate particle sizes and cement contents on the internal structure of pervious concrete were investigated. Accordingly, test blocks with different aggregate particle sizes and cement contents were dissected and photographed. Subsequently, the captured images were processed using the ImageJ software (1.53i) to analyze the profiles of the test blocks and identify the internal mesoscopic parameters of the pervious concrete. This study discusses the relationship between microscopic parameters and macroscopic factors based on experimental results. It also fits functional equations linking the permeability coefficient with pore parameters, matrix parameters, and compressive strength. The results indicated that, as the aggregate size increased, the internal pore diameter of the pervious concrete increased, whereas the total area and width of the cement matrix decreased. This resulted in a low permeability coefficient and high compressive strength of the test block. Increasing the cement content in pervious concrete reduced the porosity and increased the width and area of the internal matrix. Consequently, the permeability coefficient decreased, and the compressive strength of the test block increased.

19.
Artigo em Inglês | MEDLINE | ID: mdl-38573719

RESUMO

Participants in an eye-movement experiment performed a modified version of the Landolt-C paradigm (Williams & Pollatsek, 2007) to determine if there are preferred viewing locations when they searched for target squares embedded in linear arrays of spatially contiguous clusters of squares (i.e., sequences of one to four squares having missing segments of variable size and orientation). The results of this experiment indicate that, although the peaks of the single- and first-of-multiple-fixation landing-site distributions were respectively located near the centers and beginnings of the clusters, thereby replicating previous patterns that have been interpreted as evidence for the default saccadic-targeting hypothesis, the same dissociation was evident on nonclusters (i.e., arbitrarily defined regions of analysis). Furthermore, properties of the clusters (e.g., character number and gap size) influenced fixation durations and forward saccade length, suggesting that ongoing stimulus processing affects decisions about when and where (i.e., how far) to move the eyes. Finally, results of simulations using simple oculomotor-based, default-targeting, and dynamic-adjustment models indicated that the latter performed better than the other two, suggesting that the dynamic-adjustment strategy likely reflects the basic perceptual and motor constraints shared by a variety of visual tasks, rather than being specific to Chinese reading. The theoretical implications of these results for existing and future accounts of eye-movement control are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

20.
Front Biosci (Landmark Ed) ; 29(4): 163, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38682179

RESUMO

BACKGROUND: Glucocorticoids (GCs) are commonly used as the primary chemotherapy for lymphoid malignancies, including acute lymphoblastic leukemia (ALL). However, the development of GC resistance limits their prolonged use. METHODS: In this study, we investigated the potential of a newly synthesized indole derivative called LWX-473, in combination with the classic GC Dexamethasone (DEX), to enhance the responsiveness of Jurkat cells to GC treatment. RESULTS: Our findings demonstrate that LWX-473 alone or in combination with DEX significantly improves GC-induced cell apoptosis and arrests the cell cycle in the G1 phase. Notably, the combination of LWX-473 and DEX exhibits superior efficacy in killing Jurkat cells compared to LWX-473 alone. Importantly, this compound demonstrates reduced toxicity towards normal cells. CONCLUSIONS: Our study reveals that LWX-473 has the ability to restore the sensitivity of Jurkat cells to DEX by modulating the mitochondrial membrane potential, activating the expression of DEX-liganded glucocorticoid receptor (GR), and inhibiting key molecules in the JAK/STAT signaling pathway. These findings suggest that LWX-473 could be a potential therapeutic agent for overcoming GC resistance in lymphoid malignancies.


Assuntos
Apoptose , Dexametasona , Resistencia a Medicamentos Antineoplásicos , Glucocorticoides , Indóis , Potencial da Membrana Mitocondrial , Receptores de Glucocorticoides , Humanos , Células Jurkat , Apoptose/efeitos dos fármacos , Dexametasona/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glucocorticoides/farmacologia , Indóis/farmacologia , Receptores de Glucocorticoides/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
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