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1.
Adv Healthc Mater ; : e2400307, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38573778

RESUMEN

Ferroptosis induction is an emerging strategy for tumor therapy. Reactive oxygen species (ROS) can induce ferroptosis but are easily consumed by overexpressed glutathione (GSH) in tumor cells. Therefore, achieving a large amount of ROS production in tumor cells without being consumed is key to efficiently inducing ferroptosis. In this study, a self-amplifying ferroptosis-inducing therapeutic agent, Pd@CeO2-Fe-Co-WZB117-DSPE-PEG-FA (PCDWD), is designed for tumor therapy. PCDWD exhibits excellent multi-enzyme activities due to the loading of Fe-Co dual atoms with abundant active sites, including peroxidase-like enzymes, catalase-like enzymes, and glutathione oxidases (GSHOx), which undergo catalytic reactions in the tumor microenvironment to produce ROS, thereby inducing ferroptosis. Furthermore, PCDWD can also deplete GSH in tumor cells, thus reducing the consumption of ROS by GSH and inhibiting the expression of GSH peroxidase 4. Moreover, the photothermal effect of PCDWD can not only directly kill tumor cells but also further enhance its own enzyme activities, consequently promoting ferroptosis in tumor cells. In addition, WZB117 can reduce the expression of heat shock protein 90 by inhibiting glucose transport, thereby reducing the thermal resistance of tumor cells and further improving the therapeutic effect. Finally, X-ray computed tomography imaging of PCDWD guides it to achieve efficient tumor therapy.

2.
Biomed Pharmacother ; 174: 116610, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38642503

RESUMEN

Depression ranks as the fourth most prevalent global disease, with suicide incidents occurring at a younger age. Sulpiride (SUL), an atypical antidepressant drug acting as a dopamine D2 receptor antagonist and possessing anti-inflammatory properties, exhibits limited ability to penetrate the blood brain barrier (BBB). This weak penetration hampers its inhibitory effect on prolactin release in the pituitary gland, consequently leading to hyperprolactinemia. In order to enhance the central nervous system efficacy of sulpiride and reduce serum prolactin levels, we covalently linked sulpiride to VPALR derived from the nuclear DNA repair protein ku70. In vivo study on depressive mice using intraperitoneal injection of VPALR-SUL demonstrated a significant increase in struggle time and total distance compared to those treated with only sulpiride while also reducing serum prolactin concentration. The pharmacokinetic study results showed that VPALR-SUL prolonged half-life and increased bioavailability. In conclusion, VPALR-SUL exhibited potential for enhancing sulpiride transport across the BBB, augmenting its antidepressant effects, and reducing serum prolactin levels. This study laid a foundation for improving sulpiride delivery and developing novel antidepressants.

3.
NPJ Parkinsons Dis ; 10(1): 70, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38548756

RESUMEN

This study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson's disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625-0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403-0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896-1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson's disease (OR: 0.801, 95%CI: 0.570-1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS.

4.
Microbiol Spectr ; : e0295523, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38497713

RESUMEN

In this study, we first time sequenced and analyzed the 16S rRNA gene data of predator ladybird beetles Novius pumilus and globally distributed invasive pest Icerya aegyptiaca at different stages, and combined data with bacterial genome sequences in N. pumilus to explored the taxonomic distribution, alpha and beta diversity, differentially abundant bacteria, co-occurrence network, and putative functions of their microbial community. Our finding revealed that Candidatus Walczuchella, which exhibited a higher abundance in I. aegyptiaca, possessed several genes in essential amino acid biosynthesis and seemed to perform roles in providing nutrients to the host, similar to other obligate symbionts in scale insects. Lactococcus, Serratia, and Pseudomonas, more abundant in N. pumilus, were predicted to have genes related to hydrocarbon, fatty acids, and chitin degradation, which may assist their hosts in digesting the wax shell covering the scale insects. Notably, our result showed that Lactococcus had relatively higher abundances in adults and eggs compared to other stages in N. pumilus, indicating potential vertical transmission. Additionally, we found that Arsenophonus, known to influence sex ratios in whitefly and wasp, may also function in I. aegyptiaca, probably by influencing nutrient metabolism as it similarly had many genes corresponding to vitamin B and essential amino acid biosynthesis. Also, we observed a potential horizontal transfer of Arsenophonus between the scale insect and its predator, with a relatively high abundance in the ladybirds compared to other bacteria from the scale insects.IMPORTANCEThe composition and dynamic changes of microbiome in different developmental stages of ladybird beetles Novius pumilus with its prey Icerya aegyptiaca were detected. We found that Candidatus Walczuchella, abundant in I. aegyptiaca, probably provide nutrients to their host based on their amino acid biosynthesis-related genes. Abundant symbionts in N. pumilus, including Lactococcus, Serratia, and Pseudophonus, may help the host digest the scale insects with their hydrocarbon, fatty acid, and chitin degrading-related genes. A key endosymbiont Arsenophonus may play potential roles in the nutrient metabolisms and sex determination in I. aegyptiaca, and is possibly transferred from the scale insect to the predator.

5.
Pers Soc Psychol Bull ; : 1461672241236983, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38506187

RESUMEN

Previous studies have reported mixed findings on how and why unethical behavior affects self-esteem. To address this issue, a contingent dual-process model is proposed and tested. The model postulates a negative impact of unethical behavior on self-esteem through decreased morality, a positive effect through increased competence, and the relative strength of these two paths depending on system-justifying motives. Studies using unethical behavior for self-interest (Studies 1 and 2), involving ingroup interest (Study 3), and measuring (Studies 1 and 3) and manipulating general system justification (Study 2) provide support for the model. By identifying the effects of system-justifying motives and linking the two competing paths, the model reconciles inconsistencies in previous research regarding how self-esteem is influenced by unethical behavior and reveals the underlying mechanism of this association. Accordingly, the current research constructs a motivational and superordinate framework to clarify the dynamic consequences of unethical behavior.

6.
Orthop Rev (Pavia) ; 16: 94275, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38505135

RESUMEN

Purpose: Infrapatellar pole fractures are challenging injuries that require appropriate treatment to ensure optimal functional outcomes. This study aimed to introduce the application of the Suture Bridge technique using the 5-Ethibond for the treatment of infrapatellar patella fracture. Methods: Five cases of infrapatellar pole fracture that were treated at our institution between February 2020 and September 2021. The patients included one male and four females, with an average age of 66 years (range: 60-77 years). All patients were treated with the Suture Bridge technique using the 5-Ethibond to preserve the infrapatellar pole. Results: The average operative time was 64 min (range: 50-80 min). The average blood loss during surgery was 51 mL (range: 40-60 mL). All cases demonstrated fracture healing at an average of 10 weeks (range 8-12) after surgery. The patients were followed up for an average period of 14.8 months (8-22). No wound infection or second displacement of fracture fragment was found. Full range of motion was restored in all patients within 12-14 weeks after surgery. None of the patients complained of anterior knee pain. Conclusions: Based on the findings of the study, it appears that the Suture Bridge technique using 5-Ethibond is a promising and viable option for the treatment of infrapatellar pole fractures.

7.
ACS Appl Mater Interfaces ; 16(12): 15298-15307, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38488122

RESUMEN

Functional materials that can quickly absorb and degrade mustard gas are essential for chemical warfare emergency response kits. In this study, a fiber membrane with excellent adsorption and catalytic degradation activity was developed by solution blow spinning polystyrene (PS)/polyurethane (PU) and hydrothermal in situ growth of a zirconium-based MOF (MOF-808). The mechanical properties of the PS/PU fibers were improved by adding a trimethylolpropane tris (2-methyl-1-aziridine propionate) (TTMA) cross-linking agent. Moreover, the C═O bonds in TTMA provided abundant growth sites for MOF-808 in the hydrothermal process, thereby greatly increasing the loading capacity. The fiber surface was completely covered with the MOF-808 particles within 24 h. The PS/PU/TTMA/MOF-808 fiber membrane was used for the catalytic degradation of 2-chloroethyl ethyl sulfide (CEES). The degradation efficiency reached 97.7% after 72 h, indicating its great application potential in emergency wiping cloths for mustard gas adsorption and degradation.

8.
Health Sci Rep ; 7(3): e1947, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38440261

RESUMEN

Background and Aims: It is demonstrated that lipid metabolism disorders are associated with the reproductive performances of assisted reproductive technology. However, it is little known whether hyperlipidemia is associated with the endometrial receptivity and pregnancy outcomes of patients undergoing frozen-thawed embryo transfer (FET). Methods: This was a retrospective analysis involving 554 infertile women undergoing FET. The patients were divided into the hyperlipidemia group (n = 224) and control group (n = 320) based on the levels of serum lipids. The clinical and laboratory indexes between the two groups were compared. Meanwhile, the stratified analysis based on body mass index (BMI) and endometrial preparation protocols was performed. The independent samples t-test, Mann-Whitney U test, χ2 test and multiple logistic regression analysis were used to compare and analyze the data. Results: The patients with hyperlipidemia had significantly higher serum lipids levels and BMI and lower clinical pregnancy and implantation rates than those with normal blood lipids (p < 0.05). The impact of hyperlipidemia on pregnancy outcomes was independent of BMI. The multiple logistic regression analysis showed that higher cholesterol was associated with lower pregnancy rate and implantation rate (p < 0.05). Regardless of blood lipid levels, the patients undergoing the hormone replacement therapy (HRT) protocol had higher estradiol levels and lower progesterone levels compared with the stimulated cycles (STC) (p < 0.05). Moreover, the clinical pregnancy rate and implantation rate of the HRT protocol were higher than those of the STC, although there was no significant difference between the two. Conclusion: Hyperlipidemia especially higher cholesterol has a negative effect on the pregnancy outcomes of the patients undergoing FET. Actively implementing lipid-lowering treatment and the HRT protocol seem more friendly for these patients.

9.
BMC Psychol ; 12(1): 112, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38429758

RESUMEN

BACKGROUND: Identifying moral behavior in complex situations is the key ability for children to develop prosocial behavior. The theory of mind (ToM) and empathy provide the cognition and emotional motivation required for the development of moral sensitivity. In this study, we investigated the associations among ToM, empathy, and moral sensitivity and explored the possible differences between Chinese preschool children aged 4 and 5 years. METHODS: One hundred and thirty children completed the unexpected-content and change-of-location tasks as well as questionnaires about empathy and moral sensitivity individually. A one-way analysis of variance and the multi-group mediation SEM were used to examine the associations of the three variables and age differences. RESULTS: The scores of 5-year-old children in the dimensions of care, fairness, authority, and sanctity and the total score were higher than those of 4-year-old children. Moral sensitivity was positively correlated with both ToM and empathy after we controlled for verbal IQ and gender. Multigroup mediation analyses showed age-based differences in the associations among moral sensitivity, ToM, and empathy. Empathy's mediation effect was partial among 4-year-old children and complete among 5-year-old children. CONCLUSIONS: These findings contribute to understanding the cognitive and emotional factors in the formation of children's moral sensitivity. They also point to a promising approach to promoting the development of moral sensitivity and evidence for educators to understand the process of children's socialization.


Asunto(s)
Empatía , Teoría de la Mente , Humanos , Preescolar , Principios Morales , Emociones , China
10.
J Biol Chem ; 300(4): 107199, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38508309

RESUMEN

Porcine reproductive and respiratory syndrome virus (PRRSV), a highly infectious virus, causes severe losses in the swine industry by regulating the inflammatory response, inducing tissue damage, suppressing the innate immune response, and promoting persistent infection in hosts. Interleukin-13 (IL-13) is a cytokine that plays a critical role in regulating immune responses and inflammation, particularly in immune-related disorders, certain types of cancer, and numerous bacterial and viral infections; however, the underlying mechanisms of IL-13 regulation during PRRSV infection are not well understood. In this study, we demonstrated that PRRSV infection elevates IL-13 levels in porcine alveolar macrophages. PRRSV enhances m6A-methylated RNA levels while reducing the expression of fat mass and obesity associated protein (FTO, an m6A demethylase), thereby augmenting IL-13 production. PRRSV nonstructural protein 9 (nsp9) was a key factor for this modulation. Furthermore, we found that the residues Asp567, Tyr586, Leu593, and Asp595 were essential for nsp9 to induce IL-13 production via attenuation of FTO expression. These insights delineate PRRSV nsp9's role in FTO-mediated IL-13 release, advancing our understanding of PRRSV's impact on host immune and inflammatory responses.

11.
Heliyon ; 10(4): e26209, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38390181

RESUMEN

The investigation of peptide drugs has become essential in the development of innovative medications for hypertension. In this study, a sensitive high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method was developed to determine the plasma concentration and stability of the antihypertensive peptide FR-6 in rats. An isotopically labeled peptide (with an unchanged sequence) was utilized as an internal standard (IS) for validation purposes. Subsequently, this assay was employed to examine the pharmacokinetics of different administration methods (tail vein and gavage) in Sprague Dawley (SD) rats. Extracted plasma samples underwent sample preparation through methanol protein precipitation, followed by elution of FR-6 on Wondasil C18 Superb column (4.6 × 150 mm, 5 µm), using a mobile phase consisting of formic acid (0.1%) in water (A) and formic acid (0.125%)-ammonium formate (2 mM) in methanol (B). Ion pairs corresponding to FR-6 and IS were monitored via multiple reaction monitoring (MRM) under positive ion mode: m/z 400.7 â†’ 285.1 for FR-6 and m/z 406.1 â†’ 295.1 for IS detection respectively. The method exhibited excellent linearity with respect to FR-6 concentrations. In addition, the inter-day and intra-day precision were 0.61-6.85% and 1.76-11.75%; the inter-day and intra-day accuracy were -7.28-0.13% and -7.20-2.28%, respectively. In conclusion, the matrix effect, extraction recovery, and stability data were validated according to FDA recommended acceptance criteria for bioanalytical methods. This validated method serves as a reliable tool for determining the concentration of antihypertensive peptide FR-6, and has been successfully applied in pharmacokinetic studies involving rats.

12.
Angew Chem Int Ed Engl ; 63(12): e202317304, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38298089

RESUMEN

Pyroptosis is an effective anti-tumor strategy. However, monometallic pyroptosis biotuners have not been explored until now. Here, we discover for the first time that biodegradable monometallic Al can act as a pyroptosis biotuner for tumor therapy. pH-sensitive Al nanoparticles (Al@P) are obtained by equipping polyethylene glycol-b-(poly(methyl methacrylate)-co-poly(4-vinylpyridine), which can exert their effect at the tumor site without affecting normal cells. The H2 and Al3+ release by Al@P in the acidic environment of tumors disrupts the redox balance and ionic homeostasis in tumor cells, thus generating large amounts of reactive oxygen species (ROS), leading to caspase-1 activation, gasdermin D cleavage, and IL-1ß/LDH release, which induces canonical pyroptotic death. Meanwhile, the prodrug Doxorubicin (Pro-DOX) is successfully loaded onto Al@P (Al@P-P) and can be activated by ROS to release DOX in the tumor cells, thus further improving the tumor-killing efficiency. Ultimately, Al@P-P is degradable and exhibits efficient tumor inhibition.


Asunto(s)
Metacrilatos , Neoplasias , Polietilenglicoles , Piroptosis , Humanos , Aluminio/farmacología , Especies Reactivas de Oxígeno , Neoplasias/tratamiento farmacológico , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico
13.
Int Ophthalmol ; 44(1): 34, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38332205

RESUMEN

PURPOSE: To explore the associations between central anterior chamber depth (CACD) and other anterior segment biometric parameters and to determine the possible determinants of CACD in short, normal, and long eyes. METHODS: The biometric data of pre-operation patients aged 50-80 years with coexisting cataract and primary angle-closure disease or senile cataract were reviewed. Axial length (AL), CACD, lens thickness (LT), central corneal thickness (CCT), and white-to-white distance (WTW) were measured by Lenstar optical biometry (Lenstar 900). The data of 100 normal eyes (AL = 22 to 26 mm), 100 short eyes (AL ≤ 22 mm), and 100 long eyes (AL ≥ 26 mm) were consecutively collected for subsequent analyses. RESULTS: The mean age of the subjects was 66.60 ± 7.85 years, with 25.7% of the sample being men. Both CACD and WTW were found to be smallest in short eyes and were smaller in normal eyes than in long eyes (F = 126.524, P < 0.001; F = 28.458, P < 0.001). The mean LT was significantly thicker in short eyes than in normal and long eyes (4.66 mm versus 4.49 mm versus 4.40 mm; F = 18.099, P < 0.001). No significant differences were observed in CCT between the three AL groups (F = 2.135, P = 0.120). Stepwise regression analysis highlighted AL, LT, and WTW as three independent factors associated with CACD in the normal AL group. In the short AL group and long AL group, LT and WTW were independent factors associated with CACD. CONCLUSIONS: CACD increases as AL elongates and reaches a peak when AL exceeds 26 mm. Furthermore, CACD showed inverse correlation with LT and positive correlation with WTW. A relatively small WTW results in an anteriorly positioned lens, and thus, a decrease in CACD.


Asunto(s)
Catarata , Cristalino , Lentes Intraoculares , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , Cristalino/diagnóstico por imagen , Catarata/complicaciones , Catarata/diagnóstico , Biometría/métodos , Cámara Anterior/diagnóstico por imagen , Longitud Axial del Ojo
14.
Microb Biotechnol ; 17(2): e14416, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38381051

RESUMEN

Many traditional fermented foods and beverages industries around the world request the addition of multi-species starter cultures. However, the microbial community in starter cultures is subject to fluctuations due to their exposure to an open environment during fermentation. A rapid detection approach to identify the microbial composition of starter culture is essential to ensure the quality of the final products. Here, we applied single-cell Raman spectroscopy (SCRS) combined with machine learning to monitor Oceanobacillus species in Daqu starter, which plays crucial roles in the process of Chinese baijiu. First, a total of six Oceanobacillus species (O. caeni, O. kimchii, O. iheyensis, O. sojae, O. oncorhynchi subsp. Oncorhynchi and O. profundus) were detected in 44 Daqu samples by amplicon sequencing and isolated by pure culture. Then, we created a reference database of these Oceanobacillus strains which correlated their taxonomic data and single-cell Raman spectra (SCRS). Based on the SCRS dataset, five machine-learning algorithms were used to classify Oceanobacillus strains, among which support vector machine (SVM) showed the highest rate of accuracy. For validation of SVM-based model, we employed a synthetic microbial community composed of varying proportions of Oceanobacillus species and demonstrated a remarkable accuracy, with a mean error was less than 1% between the predicted result and the expected value. The relative abundance of six different Oceanobacillus species during Daqu fermentation was predicted within 60 min using this method, and the reliability of the method was proved by correlating the Raman spectrum with the amplicon sequencing profiles by partial least squares regression. Our study provides a rapid, non-destructive and label-free approach for rapid identification of Oceanobacillus species in Daqu starter culture, contributing to real-time monitoring of fermentation process and ensuring high-quality products.


Asunto(s)
Algoritmos , Espectrometría Raman , Reproducibilidad de los Resultados , Bases de Datos Factuales , Aprendizaje Automático
15.
Environ Sci Pollut Res Int ; 31(11): 16884-16898, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38329664

RESUMEN

With increasing concerns about climate change and resource-environmental limitations, the green development of the mining industry has become mainstream and gained much support. Driven by the concept of sustainable and green development, China has made the advancement of green mine construction a crucial part of establishing an eco-society and has put forward the overall goal of green mines. An important future strategy is to evaluate a large number of mines. However, developing scientific, reliable, and comprehensive index systems and evaluation methods is extremely difficult because of the objective complexity of green mine evaluation and the fuzziness of some indicators. The kernel method and intuitionistic fuzzy set can effectively handle these problems. This study proposed a comprehensive evaluation index system and a hybrid evaluation method based on the kernel distance measure and intuitionistic fuzzy TOPSIS method. The index system contains 22 indicators considering six aspects: mining area environment, resource development mode, comprehensive utilization of resources, energy saving and emission reduction, technical innovation, and corporation management. The hybrid evaluation method was applied to the practical assessment of ten green mines in Panxi, China. Comparative analyses were carried out to demonstrate its applicability and sensitivity. The results verify that the hybrid method can fully depict the construction achievements of green mines in all aspects with strong reliability and stability. This approach is a valuable reference for evaluators and decision-makers in government departments.


Asunto(s)
Lógica Difusa , Reproducibilidad de los Resultados , China
16.
Adv Mater ; : e2310421, 2024 Jan 25.
Artículo en Inglés | MEDLINE | ID: mdl-38270289

RESUMEN

Vascular microenvironment is found to be closely related to immunotherapy efficacy. Identification and ultrasound imaging of the unique vascular characteristics, able to predict immune microenvironment, is important for immunotherapy decision-making. Herein, it is proved that high CD93 expression in the tumor vessels is closely related to the poor immune response of prostate cancer. For ultrasound molecular imaging of CD93, CD93-targeted microbubbles (MBs) consist a gaseous core and the MMRN2 (Multimerin-2) containing cell membrane (CM) /lipid hybrid membrane is then synthesized. In vitro and in vivo assays demonstrate that these MBs can recognize CD93 efficiently and then accumulate within tumor regions highly expressing CD93. Contrast-enhanced ultrasound (CEUS) imaging with CD93-targeted MBs demonstrates that targeted ultrasound intensity is negatively related to inflammatory tumor immune microenvironment (TIME) and cytotoxic T cell infiltration. Together, endothelial expression of CD93 in tumor is a unique predictor of immunosuppressive microenvironment and CD93-targeted MBs have a great potential to evaluate tumor immune status.

17.
Adv Sci (Weinh) ; 11(12): e2305891, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38263860

RESUMEN

PDL1 blockade therapy holds great promise in cancer immunotherapy. Ultrasound imaging of PDL1 expression in the tumor is of great importance in predicting the therapeutic efficacy. As a proof-of-concept study, a novel ultrasound contrast agent has been innovated here to image and block PDL1 in the tumor tissue. Briefly, extracellular vesicles (EVs) are engineered to display truncated PD1 (tPD1) on the surface to bind PDL1 with high affinity by fusion to EV-abundant transmembrane protein PTGFRN. The engineered EVs are then encapsulated with Ca(HCO3)2 via electroporation and designated as Gp-EVtPD1, which would recognize PDL1 highly expressed cells and produce gas in the endosomes and lysosomes. On the one hand, the echogenic signal intensity correlates well with the PDL1 expression and immune response inhibition in the tumor. On the other hand, during the trajectory of Gp-EVtPD1 in the recipient cells, tPD1 on the EV binds PDL1 and triggers the PDL1 endocytosis and degradation in endosomes/lysosomes in a sequential manner, and thus boosts the anti-tumor immunity of cytotoxic T cells. In summary, Gp-EVtPD1 serves as a novel ultrasound contrast agent and blocker of PDL1, which might be of great advantage in imaging PDL1 expression and conquering immune checkpoint blocker resistance.


Asunto(s)
Vesículas Extracelulares , Neoplasias , Humanos , Medios de Contraste , Inmunoterapia/métodos , Ultrasonografía
18.
Psychol Rep ; : 332941241226907, 2024 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-38193445

RESUMEN

Nomophobia is the state of being anxious or disturbed when feeling disconnected from the digital world and can have a significant impact on individuals' health and well-being. Drawing upon attachment theory and the previous literature on nomophobia, this study aims to understand how attachment anxiety influences nomophobia and whether this relationship differs between males and females. In the Human Penguin Project (HPP) (N = 1221; 12 countries; participants aged ≥20 years), the Experiences in Close Relationships Questionnaire-Revised (ECR-R), the Toronto Alexithymia Scale (TAS-20), the Perceived Stress Scale (PSS), and the Nomophobia Questionnaire (NMP-Q) were used to assess attachment anxiety, alexithymia, perceived stress, and nomophobia, respectively. The results demonstrated that (1) there were significant positive correlations between attachment anxiety, nomophobia, alexithymia, and perceived stress. Additionally, (2) there was a direct and significant effect of attachment anxiety on nomophobia, and alexithymia and perceived stress partially mediated this relationship. Finally, (3) gender significantly moderated the relationship between attachment anxiety and nomophobia. Specifically, the predicted effect was significant in both males and females, but the direct effect of attachment anxiety and nomophobia was stronger in males.

19.
NAR Cancer ; 6(1): zcad063, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38213995

RESUMEN

Cis-regulatory elements (CREs) and super cis-regulatory elements (SCREs) are non-coding DNA regions which influence the transcription of nearby genes and play critical roles in development. Dysregulated CRE and SCRE activities have been reported to alter the expression of oncogenes and tumor suppressors, thereby regulating cancer hallmarks. To address the strong need for a comprehensive catalogue of dysregulated CREs and SCREs in human cancers, we present TSCRE (http://tscre.zsqylab.com/), an open resource providing tumor-specific and cell type-specific CREs and SCREs derived from the re-analysis of publicly available histone modification profiles. Currently, TSCRE contains 1 864 941 dysregulated CREs and 68 253 dysregulated SCREs identified from 1366 human patient samples spanning 17 different cancer types and 9 histone marks. Over 95% of these elements have been validated in public resources. TSCRE offers comprehensive annotations for each element, including associated genes, expression patterns, clinical prognosis, somatic mutations, transcript factor binding sites, cancer-type specificity, and drug response. Additionally, TSCRE integrates pathway and transcript factor enrichment analyses for each study, enabling in-depth functional and mechanistic investigations. Furthermore, TSCRE provides an interactive interface for users to explore any CRE and SCRE of interest. We believe TSCRE will be a highly valuable platform for the community to discover candidate cancer biomarkers.

20.
Sci Rep ; 14(1): 1064, 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38212380

RESUMEN

This paper proposes a fluid classifier for a tight reservoir using a quantum neural network (QNN). It is difficult to identify the fluid in tight reservoirs, and the manual interpretation of logging data, which is an important means to identify the fluid properties, has the disadvantages of a low recognition rate and non-intelligence, and an intelligent algorithm can better identify the fluid. For tight reservoirs, the logging response characteristics of different fluid properties and the sensitivity and relevance of well log parameter and rock physics parameters to fluid identification are analyzed, and different sets of input parameters for fluid identification are constructed. On the basis of quantum neural networks, a new method for combining sample quantum state descriptions, sensitivity analysis of input parameters, and wavelet activation functions for optimization is proposed. The results of identifying the dry layer, gas layer, and gas-water co-layer in the tight reservoir in the Sichuan Basin of China show that different input parameters and activation functions affect recognition performance. The proposed quantum neural network based on hybrid parameters and a wavelet activation function has higher fluid identification accuracy than the original quantum neural network model, indicating that this method is effective and warrants promotion and application.

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