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BACKGROUND: A dramatic increase in fetal situs inversus diagnoses by ultrasound in the months following the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surge of December 2022 in China led us to investigate whether maternal SARS-CoV-2 exposure could be associated with elevated risk of fetal situs inversus. METHODS: In this multi-institutional, hospital-based, matched case-control study, we investigated pregnant women who underwent ultrasonographic fetal biometric assessment at gestational weeks 20-24 at our hospitals. Each pregnant woman carrying a situs inversus fetus was randomly matched with four controls based on the date of confinement. Relevant information, including SARS-CoV-2 infection, and other potential risk factors were collected. Conditional logistic regression was used to test possible associations between fetal situs inversus and SARS-CoV-2 infection at different gestational weeks as well as individual risk factors. FINDINGS: A total of 52 pregnant women diagnosed with fetal situs inversus between January 1 and October 31, 2023 and 208 matched controls with normal fetuses were enrolled. We found no association between an increased risk of fetal situs inversus with gestational SARS-CoV-2 infection or with other risk factors. However, fetal situs inversus was significantly associated with SARS-CoV-2 infection specifically in gestational weeks 4-6 (adjusted odds ratio [aOR] 6.54 [95% confidence interval 1.76-24.34]), but not with infection at other gestational ages, after adjusting for covariates. CONCLUSIONS: Increased risk of fetal situs inversus is significantly associated with maternal SARS-CoV-2 infection at gestational weeks 4-6, corresponding to the fetal developmental window for visceral lateralization in humans. FUNDING: National Key R&D Program of China, etc.
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Background: Aucklandiae Radix (CAR) and its roasted processed products (PAR) are extensively used in various Chinese patent medicines due to their diverse pharmacological activities. However, numerous side effects of CAR have been reported and the hepatotoxicity and the corresponding mechanisms have not been thoroughly investigated. Our study aims to explore the underlying mechanism of the hepatotoxic impacts of CAR. Methods: In this study, metabolomic analysis was performed using liver tissue from the mice administered with different dosages of CAR/PAR extracts to examine the hepatotoxic impacts of CAR and elucidate the underlying mechanism. Network pharmacology was employed to predict the potential molecular targets and associated signaling pathways based on the distinctive compounds between CAR and PAR. A composition-target-GO-Bio process-metabolic pathway network was constructed by integrating the hepatotoxicity-related metabolic pathways. Finally, the target proteins related with the hepatotoxic effect of CAR were identified and validated in vivo. Results: The metabolomics analysis revealed that 33 related metabolic pathways were significantly altered in the high-dose CAR group, four of which were associated with the hepatotoxicity and could be alleviated by PAR. The network identified NQO1 as the primary target of the hepatotoxic effect induced by CAR exposure, which was subsequently verified by Western Blotting. Further evidence in vivo demonstrated that Nrf2 and HO-1, closely related to NQO1, were also the main targets through which CAR induced the liver injury, and that oxidative stress should be the primary mechanism for the CAR-induced hepatotoxicity. Conclusions: This preliminary study on the hepatic toxic injury of CAR provides a theoretical basis for the rational and safe use of CAR rationally and safely in clinical settings.
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Status researchers have recognized virtue, competence, and dominance as distinct, viable routes to attaining status. While acknowledging that these routes could be compatible and may not operate independently, prior research relying on a variable-centered perspective has largely neglected their potentially complex interactions. This article integrates a person-centered perspective with the variable-centered perspective to explore how different routes conjointly shape workplace status. Study 1A (N = 537) employs latent profile analysis, an inductive person-centered method, to re-analyze existing survey data, identifying seven distinct profiles of virtue, competence, and dominance that people use to attain status. Study 1B (N = 988) confirms the existence of these profiles in an independent sample of full-time U.S. workers, albeit with nuanced differences in levels. Across our initial studies, these profiles differ in status attainment, with a profile characterized by high virtue and competence but low dominance associated with the highest status-a key discovery challenging to uncover using the variable-centered approach alone. Study 2 (N = 792), a preregistered experiment manipulating the three routes in hypothetical scenarios, gathers causal evidence confirming these profiles' varying effectiveness. Study 3 (N = 785), another preregistered experiment using refined manipulations, corroborates the findings of Study 2 and provides evidence for the relevance of these causal insights to real-life workplace contexts. This research has several crucial implications: reaching the top requires a combination of multiple routes; conflating virtue and competence under the umbrella of "prestige" obscures their unique contributions; and dominance's positive effect on status is not universally applicable. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Compensation and intracellular storage of PD-L1 may compromise the efficacy of antibody drugs targeting the conformational blockade of PD1/PD-L1 on the cell surface. Alternative therapies aiming to reduce the overall cellular abundance of PD-L1 thus might overcome resistance to conventional immune checkpoint blockade. Here we show by bioinformatics analysis that colon adenocarcinoma (COAD) with high microsatellite instability (MSI-H) presents the most promising potential for this therapeutic intervention, and that overall PD-L1 abundance could be controlled via HSC70-mediated lysosomal degradation. Proteomic and metabolomic analyses of mice COAD with MSI-H in situ unveil a prominent acidic tumor microenvironment. To harness these properties, an artificial protein, IgP ß, is engineered using pH-responsive peptidic foldamers. This features customized peptide patterns and designed molecular function to facilitate interaction between neoplastic PD-L1 and HSC70. IgP ß effectively reduces neoplastic PD-L1 levels via HSC70-mediated lysosomal degradation, thereby persistently revitalizing the action of tumor-infiltrating CD8 + T cells. Notably, the anti-tumor effect of lysosomal-degradation-based therapy surpasses that of antibody-based immune checkpoint blockade for MSI-H COAD in multiple mouse models. The presented strategy expands the use of peptidic foldamers in discovering artificial protein drugs for targeted cancer immunotherapy.
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Adenocarcinoma , Antígeno B7-H1 , Neoplasias del Colon , Lisosomas , Inestabilidad de Microsatélites , Linfocitos T Citotóxicos , Microambiente Tumoral , Lisosomas/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/inmunología , Antígeno B7-H1/genética , Animales , Adenocarcinoma/inmunología , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/metabolismo , Neoplasias del Colon/inmunología , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Ratones , Humanos , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos , Linfocitos T Citotóxicos/inmunología , Línea Celular Tumoral , Proteolisis/efectos de los fármacos , Femenino , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéuticoRESUMEN
OBJECTIVE: In Guangdong Province, hepatitis C virus (HCV) had been found to confer resistance to direct-acting antivirals (DAAs). There were few studies of HCV subtypes and resistance-associated substitutions (RASs) of HCV in different high-risk populations. In this study, we aimed to determine the subtype distribution and the RASs in high-risk population groups, including drug users (DU), men who have sex with men (MSM), female sex workers (FSW), and male patients with sexually transmitted diseases (STD) in Guangdong Province (a highly developed province with a large population). METHODS: Using a city-based sampling strategy,1356 samples were obtained from different population groups. Phylogenetic analyses determined subtypes based on Core, NS5B, or NS5A sequences. HCV subtype distribution and RASs in various risk groups and regions were analyzed. RESULTS: Ten subtypes, of which 6 h and 6 k were novel in Guangdong, were identified. The primary subtype among all risk groups was 6a. RASs in 1b and 3a were different from those observed in other studies. Subtype 3b in western Guangdong was higher than the other three regions. No RASs were found in 6a or any other genotype 6. CONCLUSIONS: The HCV subtypes are expanding in high-risk populations in Guangdong. Drug use by other risk groups and commercial sex by DU may bridge the dissemination of 6a from DU to other populations. The RAS profiles of 1b and 3a differed from those reported in studies conducted in southwestern China. Further research is required to determine the reason for this discrepancy. Moreover, the combination of RASs was high in subtype 3b. To guide HCV treatment of subtype 3b, pretreatment subtyping of HCV genotype 3 should be considered in western cities in the near future.
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This study comprehensively explores the clinical characteristics, diagnostic approaches, and treatment methods for liver mucinous cystic neoplasms (MCN). A retrospective analysis was conducted on seven individuals diagnosed with MCN, admitted to the Fifth Medical Center of the PLA General Hospital between October 2016 and May 2023. Preoperative AFP was negative, while CA19-9 was elevated in two cases. Surgical resection was performed for all patients. The patients showed favorable postoperative recovery. Follow-up revealed an excellent overall survival rate, except for one case of invasive carcinoma resulting in tumor recurrence and metastasis 6 months after surgery. MCN poses a diagnostic challenge due to the absence of distinct clinical and radiological features, leading to potential misdiagnosis and inappropriate treatment. Patients with suspected liver cystic diseases should consider the possibility of MCN. Surgical resection has proven to be a practical approach with satisfactory therapeutic outcomes.
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Neoplasias Hepáticas , Humanos , Femenino , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Hígado/patología , Hígado/cirugía , Hígado/metabolismo , Hígado/diagnóstico por imagen , Resultado del TratamientoRESUMEN
There was no significant difference in the composition and content of fatty acids in eggs among different breeds initially, but following the supplementation of flaxseed oil, Dwarf Layer were observed to deposit more n-3 polyunsaturated fatty acid (PUFA) in eggs. Currently, there is limited research on the mechanisms underlying the differences in egg composition among different breeds. Therefore, in this study, 150 twenty-four-wk-old hens of each breed, including the Dwarf Layer and White Leghorn, were fed either a basal diet or a diet supplemented with 2.5% flaxseed oil. After 28 d, eggs and liver samples were collected to determine fatty acid composition, and serum, liver, intestine, and follicles were collected for subsequent biochemical, intestinal morphology, and lipid metabolism-related genes expression analysis. Duodenal contents were collected for microbial analysis. The results showed that there was no significant difference in the content and deposition efficiency of total n-3 PUFA in the liver of the 2 breeds, but the content and deposition efficiency of total n-3 PUFA in the egg of Dwarf Layer were significantly higher than those of White Leghorn after feeding flaxseed oil. Flaxseed oil and breeds did not have significant effects on cholesterol (CHO), free fatty acids (NEFA), low-density lipoprotein (LDL), and estrogen (E2) levels. After feeding with flaxseed oil, the villus height and the villus-to-crypt ratio in both breeds were increased and duodenal crypt depth was decreased. The villus-to-crypt ratio (4.78 vs. 3.60) in the duodenum of Dwarf Layer was significantly higher than that in White Leghorn after feeding with flaxseed oil. Flaxseed oil can impact the gut microbiota in the duodenum and reduce the microbiota associated with fatty acid breakdown, such as Romboutsia, Subdolibranulum, Lachnochlostridium, and Clostridium. This may mean that less ALA can be decomposed and more ALA can be absorbed into the body. Additionally, after feeding flaxseed oil, the mRNA levels of elongation enzymes 5 (ELOVL5), fatty acid desaturase 1 (FADS1), and fatty acid transporter 1 (FATP1) in the liver of Dwarf Layer were significantly higher than those in White Leghorn, while the mRNA levels of peroxisome proliferator-activated receptor alpha (PPAR), carnitine palmitoyl transferase 1 (CPT1), Acyl CoA oxidase 1 (ACOX1), and Acyl-CoA synthetase (ACSL) were significantly lower than those in White Leghorn. The mRNA level of FABP1 in the duodenum of Dwarf Layer was significantly higher than that of White Leghorn, while the mRNA level of FATP1 was significantly lower than that of White Leghorn. The protein levels of ELOVL5 in the liver of Dwarf Layer and very low-density lipoprotein receptor (VLDLR) in the follicles were significantly higher than those of White Leghorn. In summary, after feeding flaxseed oil, the higher ratio of villus height to crypt depth in Dwarf Layer allows more α-linolenic acid (ALA) to be absorbed into the body. The higher mRNA expression of FADS1, ELOVL5, and FATP1, as well as the higher protein expression of ELOVL5 in the liver of Dwarf Layer enhance the conversion of ALA into DHA. The higher protein expression of VLDLR in follicles of Dwarf Layer allows more n-3 PUFA to deposit in the follicles. These combined factors contribute to the Dwarf Layer's ability to deposit higher levels of n-3 PUFA in eggs, as well as improving the deposition efficiency of n-3 PUFA.
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Purpose: The aim of this systematic review was to (1) estimate the prevalence of adhering to the MSE guidelines (at least 2 times/days a week) among adults; and (2) synthesize evidence on the correlates of adhering to the MSE guidelines. Methods: Five electronic databases were searched (March 2022), with a total of 30 observational studies consisting of 2,629,508 participants meeting the eligibility criteria. A meta-analysis was conducted to pool the prevalence of adhering to the MSE guidelines using the results of 21 eligible studies (study aim 1); and data reporting correlates of adhering to the MSE guidelines using 12 eligible studies were synthesized and categorized based on the Socioecological Model Framework (study aim 2). Results: Overall, 22.8 % (95%CI: 18.18 % â 27.77 %) of adults adhered to the MSE guidelines, and 23 potential correlates at five levels were examined. Five variables (i.e., sex, age, education level, socioeconomic status) at the sociodemographic level and two variables (i.e., body mass index, self-rated health) at the physical related level were identified as consistent correlates, but displaying weak to moderate association strengths. Conclusions: Less than a quarter of adults meet the MSE guidelines and multidimensional correlates are associated with the adherence to the guidelines, particularly sociodemographic correlates (e.g., sex, age, and educational level). Findings highlight the need to further promote the importance of engaging in MSE among adults and investing effective interventions that not only provide opportunities for MSE for adults, but also facilitate the development of skills and confidence to engage in MSE.
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Background: Reaching movements are crucial for daily living and rehabilitation, for which Fitts' Law describes a speed-accuracy trade-off that movement time increases with task difficulty. This study aims to investigate whether cortical activation in motor-related areas is directly linked to task difficulty as defined by Fitts' Law. Understanding this relationship provides a physiological basis for parameter selection in therapeutic exercises. Methods: Sixteen healthy subjects performed 2D reaching movements using a rehabilitation robot, with their cortical responses detected using functional near-infrared spectroscopy (fNIRS). Task difficulty was manipulated by varying target size and distance, resulting in 3 levels of index-of-difficulty (ID). Kinematic signals were recorded alongside cortical activity to assess the relationship among movement time, task difficulty, and cortical activation. Results: Our results showed that movement time increased with ID by 0.2974s/bit across all subjects (conditional r2 = 0.6434, p < 0.0001), and all subjects showed individual trends conforming Fitts' Law (all p < 0.001). Neither activation in BA4 nor in BA6 showed a significant correlation with ID (p > 0.05), while both the target size and distance, as well as the interaction between them, showed a significant relationship with BA4 or BA6 activation (all p < 0.05). Conclusion: This study found that although kinematic measures supported Fitts' Law, cortical activity in motor-related areas during reaching movements did not correlate directly with task difficulty as defined by Fitts' Law. Additional factors such as muscle activation may call for different cortical control even when difficulty was identical.
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Sonodynamic therapy (SDT) has been extensively studied as a new type of non-invasive treatment for mammary cancer. However, the poor water solubility and defective biocompatibility of sonosensitizers during SDT hinder the sonodynamic efficacy. Herein, a nanoplatform has been developed to achieve high efficient SDT against mammary cancer through the host-guest interaction of ß-cyclodextrin/5-(4-hydroxyphenyl)-10,15,20-triphenylporphyrin (ß-CD-TPP) and ferrocenecarboxylic acid/chitooligosaccharides (FC-COS). Moreover, the glucose oxidase (GOx) was loaded through electrostatic adsorption, which efficiently restricts the energy supply in tumor tissues, thus enhancing the therapeutic efficacy of SDT for tumors. Under optimal conditions, the entire system exhibited favorable water solubility, suitable particle size and viable biocompatibility. This facilitated the integration of the characteristics of starvation therapy and sonodynamic therapy, resulting in efficient inhibition of tumor growth with minimal side effects in vivo. This work may provide new insights into the application of natural oligosaccharides for construct multifunctional nanocarrier systems, which could optimize the design and development of sonodynamic therapy strategies and even combination therapy strategies.
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Quitosano , Oligosacáridos , Especies Reactivas de Oxígeno , Terapia por Ultrasonido , Oligosacáridos/química , Oligosacáridos/farmacología , Animales , Quitosano/química , Quitosano/farmacología , Femenino , Especies Reactivas de Oxígeno/metabolismo , Ratones , Terapia por Ultrasonido/métodos , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacología , Ratones Endogámicos BALB C , Línea Celular Tumoral , Glucosa Oxidasa/metabolismo , Glucosa Oxidasa/química , Nanopartículas/química , Quitina/química , Quitina/análogos & derivados , Quitina/farmacología , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Compuestos Ferrosos/química , Compuestos Ferrosos/farmacología , Neoplasias de la Mama/terapia , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Metalocenos/química , Metalocenos/farmacología , Porfirinas/química , Porfirinas/farmacologíaRESUMEN
Microplastics (MPs) usually appear in the aquatic environment as complex pollutants with other environmental pollutants, such as levofloxacin (LVFX). After 45-day exposure to LVFX and MPs with different particle sizes at environmental levels, we measured the weight, snout-to-vent length (SVL), and development stages of Rana nigromaculata. Furthermore, we analyzed proteins and genes related to immune system and thyroid axis regulation, intestinal histological, and bioaccumulation of LVFX and MPs in the intestine and brain to further explore the toxic mechanism of co-exposure. We found MPs exacerbated the effect of LVFX on growth and development, and the order of inhibitory effects is as follows: LVFX-MP3>LVFX-MP1>LVFX-MP2. 0.1 and 1 µm MP could penetrate the blood-brain barrier, interact with LVFX in the brain, and affect growth and development by regulating thyroid axis. Besides, LVFX with MPs caused severer interference on thyroid axis compared with LVFX alone. However, 10 µm MP was prone to accumulating in the intestine, causing severe histopathological changes, interfering with the intestinal immune system and influencing growth and development through immune enzyme activity. Thus, we concluded that MPs could regulate the thyroid axis by interfering with the intestinal immune system.
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Sistema Inmunológico , Levofloxacino , Microplásticos , Tamaño de la Partícula , Glándula Tiroides , Animales , Glándula Tiroides/efectos de los fármacos , Microplásticos/toxicidad , Sistema Inmunológico/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidadRESUMEN
Non-small cell lung cancer (NSCLC) is characterized by a high incidence rate and poor prognosis worldwide. A deeper insight into the pathogenesis of NSCLC and identification of novel therapeutic targets are essential to improve the prognosis of NSCLC. In this study, we revealed that fibrinogen-like protein 1 (FGL1) promotes proliferation, migration, and invasion of NSCLC cells. Mechanistically, we found that Stat3 acts as a transcription factor and can be recruited to the FGL1 promoter, enhancing FGL1 promoter activity. Lysine-specific demethylase 4A (KDM4A) interacts with Stat3 and facilitates the removal of methyl groups from H3K9me3, thereby enhancing Stat3-mediated transcription of FGL1. Furthermore, we observed that Stat3 and KDM4A promote NSCLC cell proliferation, migration, and invasion partly by upregulating FGL1 expression. Additionally, the expression of FGL1 was significantly higher in cancer tissues (n = 90) than in adjacent non-cancerous tissues (n = 90). Furthermore, patients with high FGL1 expression had a shorter overall survival (OS) compared to those with low FGL1 expression. We measured the expression levels of FGL1 on circulating tumor cells (CTCs) in 65 patients and found that patients with a dynamic decrease in FGL1 expression on CTCs exhibited a better therapeutic response. These findings suggest that the dynamic changes in FGL1 expression can serve as a potential biomarker for predicting treatment efficacy in NSCLC. Overall, this study revealed the significant role and regulatory mechanisms of FGL1 in the development of NSCLC, suggesting its potential as a therapeutic target for patients with NSCLC. Future studies should provide more personalized and effective treatment options for patients with NSCLC to improve clinical outcomes.
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Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas , Progresión de la Enfermedad , Histona Demetilasas con Dominio de Jumonji , Neoplasias Pulmonares , Factor de Transcripción STAT3 , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Ratones , Animales , Histona Demetilasas con Dominio de Jumonji/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Femenino , Metástasis de la Neoplasia , Fibrinógeno/metabolismo , Fibrinógeno/genética , Masculino , Línea Celular Tumoral , Proliferación Celular , Movimiento Celular , Pronóstico , Regulación Neoplásica de la Expresión GénicaRESUMEN
Water has been recognized in promoting material removal, traditionally ascribed to friction reduction and thermal dissipation. However, the physicochemical interactions between water and the workpiece have often been overlooked. This work sheds light on how the physicochemical interactions that occur between water (H2O) and copper (Cu) workpiece influence material deformations during the cutting process. ReaxFF molecular dynamics simulations were employed as the primary method to study the atomistic physical and chemical interactions between the applied medium and the workpiece. Upon contact with the Cu surface, H2O dissociated into OH- ions, H+ ions, and traces of O2- ions. The OH- and O2- ions chemically reacted with Cu to form bonds that weakened the Cu-Cu bonds by elongation, while the H+ ions gained electrons and diffused into the Cu lattice as H- ions. The weakening of surface Cu bonds promoted plastic deformation and reduced the difficulty of material removal. Meanwhile, further addition of H2O molecules saw a plateau in hydrolysis and more dominance of H2O physical adsorption on Cu, which weakens the elongation of Cu-Cu bonds. While the ideal case for atomic-scale material removal was found with an optimal number of 240 H2O molecules, the presented Cu material state with more H2O molecules could account for the observations in microcutting. The constricted nature of physical adsorption and hydrogen ion diffusion in the surface layer prevented the propagation of dislocations through the surface, which subsequently caused pinning points to be closer together during chip formation as observed by smaller chip fold widths on the microscale. Theoretical and experimental analysis identified the importance of accounting for physicochemical interactions between surface media and the workpiece when considering material deformations at micronanoscale.
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The therapeutic response of microsatellite instability-high (MSI-H) colorectal cancer (CRC) to immune checkpoint inhibitors (ICI) is indeed surprising; however, the emergence of acquired resistance poses an even greater threat to the survival of these patients. Herein, bioinformatics analysis of MSI-H CRC samples revealed that Wnt signaling pathway represents a promising target for acquired immune reactivation, while subsequent analysis and biochemical testing substantiated the inclination of Wnt-hyperactive CRC cells to engage in macropinocytosis with human serum albumin (HSA). These findings have inspired us to develop an engineered HSA that not only possesses the ability to specifically target cancer cells but also effectively suppresses the Wnt/ß-catenin cascade within these malignant cells. In pursuit of this objective, a comprehensive screening of reported Wnt small-molecule inhibitors was conducted to evaluate their affinity with HSA, and it was discovered that Carnosic acid (CA) exhibited the highest affinity while simultaneously revealing multiple binding sites. Further investigation revealed that CA HSA the capability to engineer HSA into spherical and size-tunable nanostructures known as eHSA (Engineering HSA particle), which demonstrated optimized macropinocytosis-dependent cellular internalization. As anticipated, eHSA effectively suppressed the Wnt signaling pathway and reactivated the acquired immune response in vivo. Furthermore, eHSA successfully restored sensitivity to Anti-PD1's anticancer effects in both subcutaneous and orthotopic mouse homograft models of MSI-H CRC, as well as a humanized hu-PBMC patient-derived orthotopic xenograft (PDOX) mouse model of MSI-H CRC, all while maintaining a favorable safety profile. The collective implementation of this clinically viable immune reactivation strategy not only enables the delivery of Wnt inhibitors for CRC therapy, but also serves as an exemplary demonstration of precision-medicine-guided nanopharmaceutical development that effectively harnesses specific cellular indications in pathological states.
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Neoplasias Colorrectales , Inmunoterapia , Inestabilidad de Microsatélites , Albúmina Sérica Humana , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/metabolismo , Animales , Inestabilidad de Microsatélites/efectos de los fármacos , Ratones , Albúmina Sérica Humana/química , Vía de Señalización Wnt/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Ratones Desnudos , Proliferación Celular/efectos de los fármacosRESUMEN
Transition metal sulfides are widely used in supercapacitor electrode materials and exhibit excellent performance because of their rich variety, low price, and high theoretical specific capacity. At present, the main methods to prepare transition metal sulfides include the hydrothermal method and the electrochemical method. In order to further improve their electrochemical performance, two aspects can be addressed. Firstly, by controllable synthesis of nanomaterials, porous structures and large surface areas can be achieved, thereby improving ion transport efficiency. Secondly, by combining transition metal sulfides with other energy storage materials, such as carbon materials and metal oxides, the synergy between different materials can be fully utilized. However, future research still needs to address some challenges. In order to guide further in-depth research, it is necessary to combine the current research-derived knowledge and propose a direction for future development of transition metal sulfide electrode materials.
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In order to survive and replicate, Salmonella has evolved mechanisms to gain access to intestinal epithelial cells of the crypt. However, the impact of Salmonella Typhimurium on stem cells and progenitors, which are responsible for the ability of the intestinal epithelium to renew and protect itself, remains unclear. Given that intestinal organoids growth is sustained by stem cells and progenitors activity, we have used this model to document the effects of Salmonella Typhimurium infection on epithelial proliferation and differentiation, and compared it to an in vivo model of Salmonella infection in mice. Among gut segments, the caecum was preferentially targeted by Salmonella. Analysis of infected crypts and organoids demonstrated increased length and size, respectively. mRNA transcription profiles of infected crypts and organoids pointed to upregulated EGFR-dependent signals, associated with a decrease in secretory cell lineage differentiation. To conclude, we show that organoids are suited to mimic the impact of Salmonella on stem cells and progenitors cells, carrying a great potential to drastically reduce the use of animals for scientific studies on that topic. In both models, the EGFR pathway, crucial to stem cells and progenitors proliferation and differentiation, is dysregulated by Salmonella, suggesting that repeated infections might have consequences on crypt integrity and further oncogenesis.
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Diferenciación Celular , Receptores ErbB , Organoides , Infecciones por Salmonella , Salmonella typhimurium , Células Madre , Animales , Organoides/microbiología , Células Madre/metabolismo , Ratones , Salmonella typhimurium/patogenicidad , Salmonella typhimurium/fisiología , Infecciones por Salmonella/microbiología , Infecciones por Salmonella/patología , Receptores ErbB/metabolismo , Receptores ErbB/genética , Mucosa Intestinal/microbiología , Mucosa Intestinal/patología , Proliferación Celular , Modelos Animales de Enfermedad , Ratones Endogámicos C57BLRESUMEN
Two new cationic meso-thiazolium-BODIPY-based water-soluble and red-shifted fluorescent probes were constructed for the first time. They can monitor cellular viscosity in dual organelles and show aggregation-induced emission (AIE), which is ascribed to the efficient restricted rotation of meso-thiazolium in viscous or hindered systems. Probe 3 with an N-benzyl group shows better AIE as compared to probe 2 with an N-methyl group.
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Introduction: This study set out to understand the association between teaching practices, teacher confidence, competence, self-efficacy, and the resulting student outcomes. Methods: Data regarding teaching behaviours were collected via video recording and then evaluated using the MASTER Observation Tool. The information about demographics, self-reported teaching confidence, competence, self-efficacy, and student outcomes was collected using questionnaires. The association between teacher characteristics, and teacher and/or student outcome variables were tested using a one-way analysis of variance (ANOVA). Results: A total of ten primary schools were involved, including 597 children (age range: 10-12 years, grade 4-6) and 16 grade 4-6 PE teachers (with 16 PE classes). Most of the Physical Education (PE) lesson time was spent in training-form activities (60.2% ± 9.1), followed by instructional time (33.1% ± 8.6%), reflection (3.4% ± 2.3%), and warm-up (2.9% ± 2.0 %). It was observed that teaching behaviours and student outcomes were significantly better in urban than rural areas. Smaller class sizes (21-30 children) were found to have more positive feedback than larger ones (41-50 children). PE teachers with more than 10 years of teaching experience reported more teaching competence and self-efficacy than teachers with less than 10 years of experience. PE teachers with class sizes of 21-30 children enjoyed significantly better scores in self-efficacy than classes with 41-50 children. They also scored more highly in confidence and competence than classes with 41-50 and 51-60 pupils. Conclusion: The current study confirmed that teachers dedicated a large proportion of lesson time to PE delivering training-form activities, followed by instructional time. Teaching behaviour and student outcomes were associated with location and class size, but not gender. The study contributes to our understanding of PE instruction in Chinese primary schools and offers preliminary evidence to improve future PE teaching strategies in the country.
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BACKGROUND: Esophageal cancer (EC) metastasized to the kidney is extremely rare clinically. Here, we present a case of metachronous renal metastasis of esophageal squamous cell carcinoma (ESCC) through epithelial-mesenchymal transition (EMT). CASE PRESENTATION: A 60-year-old patient, male, complained of left waist pain for 5 days, 11 months after radical esophagectomy. Laboratory tests revealed haematuria. Both CT and PET-CT scan showed retroperitoneal lymph nodes and left renal masses. Subsequently the patient received a left nephrectomy and lymph nodes resection, and squamous cell carcinoma of kidney and renal hilar lymph nodes was diagnosed, combined with morphology, medical history and immunophenotype, it was presumed to be metastasis of ESCC through the EMT pathway. CONCLUSIONS: The renal metastasis of squamous cell carcinoma should be considered in patients with history of EC, although this is very rare. Histopathological examination combined with immunochemical detection is helpful in differential diagnosis.