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Attention is comprised of three independent and interacting attention networks: phasic alertness, orienting, and executive control. Previous studies have explored event-related potentials associated with these attention networks and executive vigilance, there is a lack of research on the relationship between executive vigilance and the three attention networks. However, there is a lack of research on the relationship between executive vigilance and the three attention networks. The present study aims to investigate this relationship. Based on the theory of cognitive resource control, two experimental blocks were designed with the vigilance task as the control variable. A total of 39 participants completed both ANTI and ANTI-V trials (two variants of the traditional attention network test ANT) in the same period. Through analysis of behavior measures (RT) and electrophysiological results related to phasic alertness (N1, P2, and contingent negative variation), orienting (P1, N1, and P3), and executive control (N2 and slow positive potential), we found that the reaction time of the ANTI block was lower than that of the ANTI-V block under all conditions, This suggests that adding a vigilance task may lead to reduced allocation of attention resources across all three attention networks. Furthermore, the orienting ability was weaker in the ANTI-V experimental block compared to that in the ANTI block due to effects on P1 and P3 regulation by the vigilance task. The N2 amplitude of the ANTI-V block was consistently reduced under similar conditions, indicating a weakening of executive control ability. The electrophysiological results revealed that executive vigilance inhibited the component of early attention perception related to the orienting network and was also related to the ability to detect conflict in the executive control network.
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Objective: The coronavirus disease 2019 (COVID-19) spread rapidly and claimed millions of lives worldwide. Acute respiratory distress syndrome (ARDS) is the major cause of COVID-19-associated deaths. Due to the limitations of current drugs, developing effective therapeutic options that can be used rapidly and safely in clinics for treating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections is necessary. This study aims to investigate the effects of two food-extracted immunomodulatory agents, ajoene-enriched garlic extract (AGE) and cruciferous vegetables-extracted sulforaphane (SFN), on anti-inflammatory and immune responses in a SARS-CoV-2 acute lung injury mouse model. Methods: In this study, we established a mouse model to mimic the SARS-CoV-2 infection acute lung injury model via intratracheal injection of polyinosinic:polycytidylic acid (poly[I:C]) and SARS-CoV-2 recombinant spike protein (SP). After the different agents treatment, lung sections, bronchoalveolar lavage fluid (BALF) and fresh faeces were harvested. Then, H&E staining was used to examine symptoms of interstitial pneumonia. Flow cytometry was used to examine the change of immune cell populations. Multiplex cytokines assay was used to examine the inflammatory cytokines.16S rDNA high-throughput sequencing was used to examine the change of gut microbiome. Results: Our results showed that AGE and SFN significantly suppressed the symptoms of interstitial pneumonia, effectively inhibited the production of inflammatory cytokines, decreased the percentage of inflammatory cell populations, and elevated T cell populations in the mouse model. Furthermore, we also observed that the gut microbiome of genus Paramuribaculum were enriched in the AGE-treated group. Conclusion: Here, for the first time, we observed that these two novel, safe, and relatively inexpensive immunomodulatory agents exhibited the same effects on anti-inflammatory and immune responses as neutralizing monoclonal antibodies (mAbs) against interleukin 6 receptor (IL-6R), which have been suggested for treating COVID-19 patients. Our results revealed the therapeutic ability of these two immunomodulatory agents in a mouse model of SARS-CoV-2 acute lung injury by promoting anti-inflammatory and immune responses. These results suggest that AGE and SFN are promising candidates for the COVID-19 treatment.
Sujet(s)
Lésion pulmonaire aigüe , Angiotensin-converting enzyme 2 , Anti-inflammatoires , Traitements médicamenteux de la COVID-19 , COVID-19 , Modèles animaux de maladie humaine , Agents immunomodulateurs , SARS-CoV-2 , Animaux , Souris , Lésion pulmonaire aigüe/immunologie , Lésion pulmonaire aigüe/traitement médicamenteux , Lésion pulmonaire aigüe/étiologie , COVID-19/immunologie , SARS-CoV-2/immunologie , Agents immunomodulateurs/pharmacologie , Agents immunomodulateurs/usage thérapeutique , Anti-inflammatoires/usage thérapeutique , Anti-inflammatoires/pharmacologie , Angiotensin-converting enzyme 2/métabolisme , Angiotensin-converting enzyme 2/génétique , Isothiocyanates/pharmacologie , Isothiocyanates/usage thérapeutique , Sulfoxydes , Humains , Cytokines/métabolisme , Glycoprotéine de spicule des coronavirus/immunologie , Poumon/immunologie , Poumon/anatomopathologie , Poumon/virologie , Poumon/effets des médicaments et des substances chimiques , Mâle , Poly I-C , Extraits de plantes/pharmacologie , Extraits de plantes/usage thérapeutiqueRÉSUMÉ
In situ vaccines (ISVs) utilize the localized delivery of chemotherapeutic agents or radiotherapy to stimulate the release of endogenous antigens from tumors, thereby eliciting systemic and persistent immune activation. Recently, a bioinspired ISV strategy has attracted tremendous attention due to its features such as an immune adjuvant effect and genetic plasticity. M13 bacteriophages are natural nanomaterials with intrinsic immunogenicity, genetic flexibility, and cost-effectiveness for large-scale production, demonstrating the potential for application in cancer vaccines. In this study, we propose an ISV based on the engineered M13 bacteriophage targeting CD40 (M13CD40) for dendritic cell (DC)-targeted immune stimulation, named H-GM-M13CD40. We induce immunogenic cell death and release tumor antigens through local delivery of (S)-10-hydroxycamptothecin (HCPT), followed by intratumoral injection of granulocyte-macrophage colony stimulating factor (GM-CSF) and M13CD40 to enhance DC recruitment and activation. We demonstrate that this ISV strategy can result in significant accumulation and activation of DCs at the tumor site, reversing the immunosuppressive tumor microenvironment. In addition, H-GM-M13CD40 can synergize with the PD-1 blockade and induce abscopal effects in cold tumor models. Overall, our study verifies the immunogenicity of the engineered M13CD40 bacteriophage and provides a proof of concept that the engineered M13CD40 phage can function as an adjuvant for ISVs.
Sujet(s)
Bactériophage M13 , Vaccins anticancéreux , Cellules dendritiques , Microenvironnement tumoral , Vaccins anticancéreux/immunologie , Microenvironnement tumoral/immunologie , Microenvironnement tumoral/effets des médicaments et des substances chimiques , Animaux , Bactériophage M13/immunologie , Bactériophage M13/composition chimique , Souris , Cellules dendritiques/immunologie , Antigènes CD40/immunologie , Antigènes CD40/métabolisme , Souris de lignée C57BL , Femelle , Lignée cellulaire tumorale , Facteur de stimulation des colonies de granulocytes et de macrophages , Antigènes néoplasiques/immunologie , HumainsRÉSUMÉ
The role of SLC35A2 in breast cancer remains poorly understood, with limited available information on its significance. This study aimed to investigate the expression of SLC35A2 and clinicopathological variables in breast cancer patients. Immunohistochemical analysis of SLC35A2 protein was conductedon 40 adjacent non-neoplastic tissues and 320 breast cancer tissues. The study also assesed the association between SLC35A2 expression and breast cancer clinicopathological features of breast cancer, as well as its impact on overall survival. In comparison to adjacent non-neoplastic tissues, a significantly higher expression of SLC35A2 was observed in breast cancer tissues (P = 0.020), and this expression was found to be independently correlated with HER2 positivity (P = 0.001). Survival analysis indicated that patients with low SLC35A2 expression had a more favorable prognosis in HER2-positive subtype breast cancer (P = 0.017). These results suggest that SLC35A2 is overexpressed in breast cancer tissues compared to adjacent non-neoplastic tissues and may serve as a potential prognostic marker for HER2-positive subtype breast cancer. Furthermore, breast cancer patients with the HER2 positive subtype who exhibited decreased levels of SLC35A2 expression demonstrated improved long-term prognostic outcomes.
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Metal pollution in sediment from construction areas raises ecological and health concerns, yet source-based sediment pollution in Bangladesh remains understudied. Our investigation focused on fifteen locations in the Kohelia River and the coastal regions near the Matarbari projects (Matarbari Power Plant, Matarbari Deep Seaport), assessing metal concentrations' sources and impacts on ecology and human well-being. Sediment quality indices indicated high Cd and Cr contamination, with sites near Matarbari projects being the most polluted. The positive matrix factorization model identified three anthropogenic sources and mixed sources. Matarbari projects contributed significantly to As (67.9 %), Mn (50.25 %), Cd (48.35 %), and Cr (41.0 %), while ship-breaking yards contributed Fe (58.0 %), Zn (55.5 %), Pb (53.8 %), and Cu (36.1 %). Ecological indices showed different impacts on aquatic life from metal pollution, but cancer risk levels stayed below the threshold set by the US Environmental Protection Agency. These findings underscore the need for targeted measures to address metal pollution.
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Surveillance de l'environnement , Sédiments géologiques , Polluants chimiques de l'eau , Bangladesh , Sédiments géologiques/composition chimique , Polluants chimiques de l'eau/analyse , Appréciation des risques , Métaux/analyse , Métaux lourds/analyse , Rivières/composition chimiqueRÉSUMÉ
Objective: Existing evidence suggests that palliative care (PC) is highly underutilized in metastatic gynecologic cancer (mGCa). This study aims to explore temporal trends and predictors for inpatient PC referral in mGCa patients who received specific critical care therapies (CCT). Methods: The National Inpatient Sample from 2003 to 2015 was used to identify mGCa patients receiving CCT. Basic characteristics were compared between patients with and without PC. Annual percentage change (APC) was estimated to reflect the temporal trend in the entire cohort and subgroups. Multivariable logistic regression was employed to explore potential predictors of inpatient PC referral. Results: In total, 122,981 mGCa patients were identified, of whom 10,380 received CCT. Among these, 1,208 (11.64%) received inpatient PC. Overall, the rate of PC referral increased from 1.81% in 2003 to 26.30% in 2015 (APC: 29.08%). A higher increase in PC usage was found in white patients (APC: 30.81%), medium-sized hospitals (APC: 31.43%), the Midwest region (APC: 33.84%), and among patients with ovarian cancer (APC: 31.35%). Multivariable analysis suggested that medium bedsize, large bedsize, Midwest region, West region, uterine cancer and cervical cancer were related to increased PC use, while metastatic sites from lymph nodes and genital organs were related to lower PC referral. Conclusion: Further studies are warranted to better illustrate the barriers for PC and finally improve the delivery of optimal end-of-life care for mGCa patients who receive inpatient CCT, especially for those diagnosed with ovarian cancer or admitted to small scale and Northeast hospitals.
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AIM: In the recent years, with the increase in the caesarean section rate, the incidence of caesarean scar pregnancy (CSP) has shown a significant upwards trend. We propose a novel, simple and rapid clinical and ultrasound (US) classification scoring system to assist in the early diagnosis of CSP. MATERIAL AND METHODS: A total of 385 patients with CSP were included in the study. All patients were given a comprehensive score, iincluding clinical data (whether HCG is consistent with gestational age and vaginal bleeding) and US findings (linea a and b, gestational sac morphology, the presence of primitive cardiac tube beat, and color Doppler aspect). The scores were analysed by ROC curve analysis, and sensitivity and specificity were calculated. RESULTS: A score of 4 has a specificity of 91.7% and a sensitivity of 95.6% in diagnose CSP. The area under the ROC curve was 0.973. CONCLUSION: This scoring system may be a reliable tool for the early diagnosis of CSP and has the characteristics of being simple and rapid. For patients with a total score of ≥4 points, CSP is suggested, and early clinical treatment can be carried out, while patients with a score of less than 4 points can temporarily retain pregnancy and be closely followed up.
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Césarienne , Grossesse extra-utérine , Grossesse , Humains , Femelle , Césarienne/effets indésirables , Cicatrice/imagerie diagnostique , Cicatrice/complications , Grossesse extra-utérine/imagerie diagnostique , Grossesse extra-utérine/étiologie , Échographie/méthodes , Diagnostic précoce , Études rétrospectivesRÉSUMÉ
Exercise preconditioning (EP) is a line of scientific inquiry into the short-term biochemical mediators of cardioprotection in the heart. This study examined the involvement of autophagy induced by energy metabolism in myocardial remodelling by EP and myocardial protection. A total of 120 healthy male Sprague Dawley (SD) rats were randomly divided into six groups. Plasma cTnI, HBFP staining and electrocardiographic indicators were examined in the context of myocardial ischemic/hypoxic injury and protection. Western blotting and fluorescence double labelling were used to investigate the relationship between energy metabolism and autophagy in EP-resistant myocardial injury caused by exhaustive exercise. Compared with those in the C group, the levels of myocardial ischemic/hypoxic injury were significantly increased in the EE group. Compared with those in the EE group, the levels of myocardial ischemic/hypoxic injury were significantly decreased in the EEP + EE and LEP + EE groups. Compared with that in the EE group, the level of GLUT4 in the sarcolemma was significantly increased, and the colocalization of GLUT4 with the sarcolemma was significantly increased in the EEP + EE and LEP + EE groups (P < 0.05). LC3-II and LC3-II/LC3-I levels of the EEP + EE group were significantly elevated compared with those in the EE group (P < 0.05). The levels of p62 were significantly decreased in the EEP + EE and LEP + EE groups compared with the EE group (P < 0.05). EP promotes GLUT4 translocation and induced autophagy to alleviate exhaustive exercise-induced myocardial ischemic/hypoxic injury.
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Conditionnement physique d'animal , Rats , Mâle , Animaux , Rat Sprague-Dawley , Myocarde/métabolisme , Autophagie , Coeur , Hypoxie/métabolismeRÉSUMÉ
Inducible costimulator ligand (ICOSL) expressed on cancer cells has immunoregulatory functions in various malignancies. However, the role of ICOSL in triple-negative breast cancer (TNBC) remains unclear. In this study, the role and expression of ICOSL in TNBC were analyzed using the cBioPortal and GEPIA databases. Then the role of ICOSL in Foxp3+ Treg cell differentiation, reversal of p38 pathway activation and cell proliferation, migration and apoptosis was determined in vitro. Finally, the effect of ICOSL expression on TNBC progression was verified in a nude mouse model of TNBC. We here observed that ICOSL expression in TNBC was found to be related to relapse-free survival, and Treg abundance was positively correlated with ICOSL expression, as demonstrated by database analyses. In vitro experiments showed that ICOSL overexpression (OE) in MDA-MB-231 cells induced cocultured T cells to differentiate into Foxp3+ Treg cells and promoted secretion of the tumor-promoting factors IL-10 and IL-4. Furthermore, in vitro experiments showed that ICOSL reversed p38 phosphorylation and promoted the proliferation, invasion, and metastasis of MDA-MB-231 ICOSL-OE cells. Finally, tumor progression was found to be promoted by ICOSL expression in a TNBC nude mouse model. Together, ICOSL expression can enhance tumor cell growth by inducing Foxp3+ Treg cell differentiation and reversing p38 pathway activation in TNBC.
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Purpose: This research aims to explore the mechanism underlying the relationship between RhoA/ROCK signaling and Connexin43 (Cx43) in retinal endothelial cell dysfunction and to evaluate the protective effect of ROCK inhibitors against retinal endothelial cell dysfunction in diabetic retinopathy (DR) models. Methods: TUNEL staining, hematoxylin and eosin staining, a retinal digestion assay, and Evans blue assay were conducted to explore the effect of fasudil in alleviating retinal dysfunction induced by DR. ELISA, the CCK-8 assay, and flow cytometry were conducted to study inflammation, viability, and apoptosis of mouse retinal microvascular endothelial cells treated with high glucose and ROCK inhibitors. The qRT-PCR and Western blotting were used to evaluate the expression of RhoA, ROCK1, ROCK2, MLC, pMLC, and Cx43. Co-immunoprecipitation was used to verify the interaction between pMLC and Cx43. Immunofluorescence and scrape-loading and dye transfer were used to evaluate the expression and function of Cx43. Results: Marked endothelial cell dysfunction resulting from the activation of RhoA/ROCK1 signaling was found in in vivo and in vitro models of DR. Via interaction with pMLC, which is downstream of RhoA/ROCK1, a significant downregulation of Cx43 was observed in retinal endothelial cells. Treatment with ROCK inhibitors ameliorated retinal endothelial dysfunction in vitro. The ROCK inhibitor, fasudil, significantly alleviated retinal dysfunction as shown by a decrease of retinal acellular capillaries, an improvement of vascular permeability, and a reduction of cell apoptosis in vivo. Conclusions: Our study highlights a novel mechanism that high glucose could activate RhoA/ROCK1/pMLC signaling, which targets the expression and localization of Cx43 and is responsible for cell viability, apoptosis, and inflammation, resulting in retinal endothelial cell injury. ROCK inhibitors markedly ameliorate endothelial cell dysfunction, suggesting their therapeutic potential for diabetic retinopathy.
Sujet(s)
Rétinopathie diabétique , rho-Associated Kinases , Animaux , Connexine 43/métabolisme , Rétinopathie diabétique/métabolisme , Cellules endothéliales/métabolisme , Glucose/métabolisme , Glucose/pharmacologie , Inflammation/métabolisme , Souris , Transduction du signal , Protéine G RhoA/métabolismeRÉSUMÉ
Based on the panel data of China Health and Retirement Longitudinal Study (CHARLS) in 2011, 2015, and 2018, this paper used the difference-in-difference (DID) method to evaluate the implementation effect how the Long-Term Care Insurance (LTCI) policy impacted on the medical expenses and the health status of the middle-aged and elder population. The empirical results show that LTCI has reduced the outpatient and inpatient quantity by 0.1689 and 0.1093 per year, and cut the outpatient and inpatient expenses by 23.9% and 19.8% per year. Moreover, the implementation of LTCI has improved the self-rated health, the activity of daily living (ADL), as well as the mental health. These conclusions verify the implementation value of LTCI system and provide policy implications for the medical reform and the further LTCI implementation in a larger scale.
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État de santé , Assurance soins de longue durée , Chine , Études longitudinales , Santé mentaleRÉSUMÉ
Retinal endothelial cells (RECs) are the primary target cells for diabetes-induced vascular damage. The P2X7/NLRP3 pathway plays an essential role in amplifying inflammation via an ATP feedback loop, promoting the inflammatory response, pyroptosis, and apoptosis of RECs in the early stages of diabetic retinopathy induced by hyperglycemia and inflammation. 3TC, a type of nucleoside reverse transcriptase inhibitor, is effective against inflammation, as it can targeting formation of the P2X7 large pore formation. Hence, our aim was to evaluated the anti-inflammatory effects and potential mechanisms of action of 3TC in vitro in retinal microvascular endothelial cells treated with high-glucose (HG) and lipopolysaccharide (LPS), as well as in vivo in the retinas of C57BL/6J male mice with streptozotocin-induced diabetes. The expression of inflammasome-related proteins P2X7 and NLRP3, and apoptosis in the retinas of 3TC-treated diabetic mice were compared to those of untreated diabetic mice. Furthermore, the anti-inflammatory, anti-apoptotic, and anti-pyroptotic effects of 3TC were evaluated in vitro in cultured mice retinal endothelial cells. Co-application of HG and LPS significantly increased the secretion of IL-6, IL-1ß, and TNF-α, and ATP levels, whereas 3TC decreased cell inflammation, apoptosis, and pyroptosis. Inhibition of P2X7R and NLRP3 inflammasome activation decreased NLRP3 inflammasome-mediated injury. 3TC prevented cytokine and ATP release following co-application of HG and LPS/BzATP. Our findings provide new insights regarding the mechanisms of action of 3TC in diabetic environment-induced retinal injury, including apoptosis and pyroptosis.
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Diabète expérimental , Rétinopathie diabétique , Adénosine triphosphate/métabolisme , Animaux , Anti-inflammatoires/métabolisme , Anti-inflammatoires/pharmacologie , Apoptose , Diabète expérimental/métabolisme , Rétinopathie diabétique/métabolisme , Cellules endothéliales/métabolisme , Inflammasomes/métabolisme , Inflammation/métabolisme , Lamivudine/métabolisme , Lipopolysaccharides/métabolisme , Lipopolysaccharides/pharmacologie , Mâle , Souris , Souris de lignée C57BL , Protéine-3 de la famille des NLR contenant un domaine pyrine/génétique , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Pyroptose , Transduction du signalRÉSUMÉ
To explore the relevant RNA-binding proteins (RBPs) and alternative splicing events (ASEs) in diabetic retinopathy (DR). We devised a comprehensive work to integrate analyses of the differentially expressed genes, including differential RBPs, and variable splicing characteristics related to DR in human retinal endothelial cells induced by low glucose and high glucose in dataset GSE117238. A total of 2320 differentially expressed genes (DEGs) were identified, including 1228 upregulated genes and 1092 downregulated genes. Further analysis screened out 232 RBP genes, and 42 AS genes overlapped DEGs. We selected high expression and consistency six RBP genes (FUS, HNRNPA2B1, CANX, EIF1, CALR, and POLR2A) for coexpression analysis. Through analysis, we found eight RASGs (MDM2, GOLGA2P7, NFE2L1, KDM4A, FAM111A, CIRBP, IDH1, and MCM7) that could be regulated by RBP. The coexpression network was conducted to further elucidate the regulatory and interaction relationship between RBPs and AS. Apoptotic progress, protein phosphorylation, and NF-kappaB cascade revealed by the functional enrichment analysis of RASGs regulated by RBPs were closely related to diabetic retinopathy. Furthermore, the expression of differentially expressed RBPs was validated by qRT-PCR in mouse retinal microvascular endothelial cells and retinas from the streptozotocin mouse model. The results showed that Fus, Hnrnpa2b1, Canx, Calr, and Polr2a were remarkedly difference in high-glucose-treated retinal microvascular endothelial cells and Fus, Hnrnpa2b1, Canx, and Calr were remarkedly difference in retinas from streptozotocin-induced diabetic mice compared to control. The regulatory network between identified RBPs and RASGs suggests the presence of several signaling pathways possibly involved in the pathogenesis of DR. The verified RBPs should be further addressed by future studies investigating associations between RBPs and the downstream of AS, as they could serve as potential biomarkers and targets for DR.
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Épissage alternatif/physiologie , Glycémie/métabolisme , Cellules endothéliales/effets des médicaments et des substances chimiques , Protéines de liaison à l'ARN/métabolisme , Rétine/effets des médicaments et des substances chimiques , Épissage alternatif/effets des médicaments et des substances chimiques , Animaux , Modèles animaux de maladie humaine , Cellules endothéliales/métabolisme , Souris , Souris de lignée NOD , Protéines de liaison à l'ARN/effets des médicaments et des substances chimiques , Réaction de polymérisation en chaine en temps réel/méthodes , Réaction de polymérisation en chaine en temps réel/statistiques et données numériques , Rétine/métabolismeRÉSUMÉ
Gel spinning is the industrial method of choice for combining hydrophilic ultra-high molecular weight (UHMW) polymer resins with a hydrophobic support polymer to produce composite filaments for cytapheresis. Cytapheresis is a medical technique for removal of leukocytes from blood. Gel spinning is used to avoid high melt viscosity and thermal sensitivity of UHMW resins and the high melt temperature of the substrate resin but requires the recovery of toxic solvents. The UHMW resin is used because it forms a stable gel phase in the presence of water; a lower molecular weight resin (LMW) simply dissolves. UHMW and LMW resins were both poly(ethylene oxide) (PEO) and the substrate was polyarylsulfone (PAS). The literature indicated PEO undergoes non-oxidative thermal degradation above 200 °C and PAS is processed up to 350 °C. Dynamic oscillatory shear rheometry was used to study 0, 25, 40, 50, 60, and 75 wt. % UHMW PEO in LMW PEO to take advantage of the sensitivity of viscosity to changes in molecular weight and material configuration, indicating degradation. Samples were exposed to 220 °C, 230 °C, 240 °C, 250 °C, 275 °C, and 300 °C temperatures for 5 min to explore conditions that could result in sample degradation. The viscosity decreased less with increasing UHMW PEO content for samples exposed to the same temperature and the viscosity decreased more with increasing exposure temperature for samples with the same UHMW PEO content. Parameters were regressed from observed data to predict the change in molecular weight via empiricisms relating the viscosity to molecular weight, shear rate, temperature, and time.
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Due to the presence of the blood-brain barrier (BBB), the delivery of general drugs into the brain tissue remains to be a tricky problem. For patients with brain metastases from breast cancer, drug delivery systems must overcome this physical barrier. Targeted nano vehicles arise as a promising alternative to deliver drugs to brain tissues successively. Herein, a dual targeting micelle drug delivery system loaded with paclitaxel (PTX) and lapatinib (LPTN) was developed for combinational therapy of brain metastases. In our study, it was shown the micelles modified with Angiopep-2 had high loading efficiency of paclitaxel and lapatinib (Ang-MIC-PTX/LP). In addition, Ang-MIC-PTX/LP could transport across the in vitro BBB model and accumulate in breast cancer cells. After intravenous injection, Ang-MIC significantly accumulated in the brain metastasis. Ang-MIC-PTX/LP could also extend the life span of brain metastasis mouse models. Overall, this study provided a promising method for treatment of brain metastases from breast cancer.
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Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Tumeurs du cerveau/traitement médicamenteux , Tumeurs du cerveau/secondaire , Tumeurs du sein/anatomopathologie , Systèmes de délivrance de médicaments , Lapatinib/administration et posologie , Micelles , Paclitaxel/administration et posologie , Animaux , Protocoles de polychimiothérapie antinéoplasique/métabolisme , Transport biologique , Barrière hémato-encéphalique/métabolisme , Encéphale/métabolisme , Tumeurs du cerveau/anatomopathologie , Modèles animaux de maladie humaine , Femelle , Humains , Injections veineuses , Lapatinib/métabolisme , Lapatinib/pharmacologie , Souris , Paclitaxel/métabolisme , Paclitaxel/pharmacologie , Peptides , Cellules cancéreuses en cultureRÉSUMÉ
Frequent marine heatwaves (MHWs), concurrent with climate warming, threaten global low-latitude, pristine coral reefs, leading to growing interest in identifying marginal coral reefs (relatively high-latitude and/or turbid reef environments) that can serve as thermal refugia from mass coral bleaching. However, the thermal refugia potential of marginal reefs remains controversial. We evaluated the thermal refugia potential of inshore reefs in the northern South China Sea (nSCS), a globally typical marginal reef system, by characterizing the long-term trend of MHW intensity and frequency and assessing thermal stress during a mass bleaching event in summer 2020. An unprecedented peak intensity of around 20 °C-weeks of cumulative heat stress, associated with a prolonged anomalous western Pacific subtropical high (WPSH) and weakened monsoon activity, induced record-breaking bleaching. The geographical variability of bleaching was strongly related to the extent of heat exposure and satellite-derived temperature anomalies. Under ongoing global warming, the frequency and intensity of MHWs over nSCS coral habitats show a markedly increasing trend, especially during the last decade. Intense MHWs and coral bleaching have already occurred throughout all El Niño-Southern Oscillation (ENSO) phases (e.g., 2010, 2015, and 2020). Climate change has pushed marginal coral reefs to or beyond the limits of their resilience, and frequent MHW events have amplified the increasing risk of thermal stress. There are no long-term thermal refugia for marginal reefs in the nSCS.
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Anthozoa , Refuge , Animaux , Récifs de corail , El Nino-oscillation australe , Réchauffement de la planète , TempératureRÉSUMÉ
The use of light-emitting diode (LED)-based photodynamic therapies in the treatment of periodontitis is increasing because these modalities are effective, safe, and painless. They are not subject to acquired drug resistance or environmental issues and are associated with no complications when used appropriately. These light sources have also been used in combination with pharmacological measures to synergize their effects and optimize therapeutic outcomes. This review focuses on optical devices used in treating periodontitis and delineates the current applications of various methods, including their utility and efficacy. The application of LEDs in periodontology is described.
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Anti-infectieux , Parodontite , Photothérapie dynamique , Antibactériens , Humains , Parodontite/traitement médicamenteux , Photothérapie dynamique/méthodes , Photosensibilisants/pharmacologie , Photosensibilisants/usage thérapeutiqueRÉSUMÉ
By using the viewpoint of modern computational algebraic geometry, we explore properties of the optimization landscapes of deep linear neural network models. After providing clarification on the various definitions of "flat" minima, we show that the geometrically flat minima, which are merely artifacts of residual continuous symmetries of the deep linear networks, can be straightforwardly removed by a generalized L2-regularization. Then, we establish upper bounds on the number of isolated stationary points of these networks with the help of algebraic geometry. Combining these upper bounds with a method in numerical algebraic geometry, we find all stationary points for modest depth and matrix size. We demonstrate that, in the presence of the non-zero regularization, deep linear networks can indeed possess local minima which are not global minima. Finally, we show that even though the number of stationary points increases as the number of neurons (regularization parameters) increases (decreases), higher index saddles are surprisingly rare.
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Exercise preconditioning (EP) can alleviate myocardial ischemic/hypoxic injury by inducing endogenous cardioprotection. Hematoxylin-eosin (HE), hematoxylin-basic fuchsin-picric acid (HBFP), and chromotrope-2R brilliant green (C-2R BG) staining have been used to visualize myocardial ischemic/hypoxic changes in previous EP studies, but comprehensive evaluation and comparisons of these methods are lacking. This study evaluated ischemic/hypoxic changes in adjacent myocardial sections by HE, HBFP, and C-2R BG and compared the characteristics of sections stained by these three methods to show changes associated with exercise-induced myocardial ischemic/hypoxic injury. Rats were randomly divided into four groups: control (C), exercise preconditioning (EP), exhaustive exercise (EE), and exercise preconditioning + exhaustive exercise (EP + EE). Adjacent myocardial sections were stained as described above and compared to evaluate the effects of exercise-induced myocardial ischemic/hypoxic injury. The three staining methods revealed consistent localization patterns of myocardial ischemic/hypoxic injury in all groups. Results suggest that EP can alleviate exhaustive exercise-induced myocardial ischemic/hypoxic injury, and the three staining methods are suitable for the histological study of exercise-induced myocardial ischemic/hypoxic injury and protection. HE staining is a simple procedure but is not specific for myocardial ischemic/hypoxic injury. HBFP and C-2R BG staining can be used to specifically visualize myocardial ischemic/hypoxic injury.
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Ischémie myocardique/métabolisme , Myocarde/métabolisme , Conditionnement physique d'animal/physiologie , Animaux , Autophagie/physiologie , Hypoxie cellulaire/physiologie , Protéine-3 liant les acides gras/métabolisme , Mâle , Rats , Rat Sprague-DawleyRÉSUMÉ
We introduce an efficient dynamical tree method that enables us to explicitly demonstrate the thermoremanent magnetization memory effect in a hierarchical energy landscape. Our simulation nicely reproduces the nontrivial waiting-time and waiting-temperature dependences in this nonequilibrium phenomenon. We further investigate the condensation effect, in which a small set of microstates dominates the thermodynamic behavior in the multilayer trap model. Importantly, a structural phase transition of the multilayer tree model is shown to coincide with the onset of the condensation phenomenon. Our results underscore the importance of hierarchical structure and demonstrate the intimate relation between the glassy behavior and structure of barrier trees.