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Synapses serve as the points of communication between neurons, consisting primarily of three components: the presynaptic membrane, synaptic cleft, and postsynaptic membrane. They transmit signals through the release and reception of neurotransmitters. Synaptic plasticity, the ability of synapses to undergo structural and functional changes, is influenced by proteins such as growth-associated proteins, synaptic vesicle proteins, postsynaptic density proteins, and neurotrophic growth factors. Furthermore, maintaining synaptic plasticity consumes more than half of the brain's energy, with a significant portion of this energy originating from ATP generated through mitochondrial energy metabolism. Consequently, the quantity, distribution, transport, and function of mitochondria impact the stability of brain energy metabolism, thereby participating in the regulation of fundamental processes in synaptic plasticity, including neuronal differentiation, neurite outgrowth, synapse formation, and neurotransmitter release. This article provides a comprehensive overview of the proteins associated with presynaptic plasticity, postsynaptic plasticity, and common factors between the two, as well as the relationship between mitochondrial energy metabolism and synaptic plasticity.
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Sinapsis , Transmisión Sináptica , Sinapsis/fisiología , Transmisión Sináptica/fisiología , Mitocondrias/metabolismo , Plasticidad Neuronal/fisiología , AutofagiaRESUMEN
Cell senescence is defined as irreversible cell cycle arrest, which can be triggered by telomere shortening or by various types of genotoxic stress. Induction of senescence is emerging as a new strategy for the treatment of cancer, especially when sequentially combined with a second senolytic drug capable of killing the resulting senescent cells, however severely suffering from the undesired off-target side effects from the senolytic drugs. Here, we prepare a bimetalic platinum-aluminum salen complex (Alumiplatin) for cancer therapy-a combination of pro-senesence chemotherapy with inâ situ senotherapy to avoid the side effects. The aluminum salen moiety, as a G-quadruplex stabilizer, enhances the salen's ability to induce cancer cell senescence and this phenotype is in turn sensitive to the cytotoxic activity of the monofunctional platinum moiety. It exhibits an excellent capability for inducing senescence, a potent cytotoxic activity against cancer cells both inâ vitro and inâ vivo, and an improved safety profile compared to cisplatin. Therefore, Alumiplatin may be a good candidate to be further developed into safe and effective anticancer agents. This novel combination of cell senescence inducers with genotoxic drugs revolutionizes the therapy options of designing multi-targeting anticancer agents to improve the efficacy of anticancer therapies.
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Aluminio , Antineoplásicos , Senescencia Celular , Etilenodiaminas , Platino (Metal) , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Etilenodiaminas/química , Etilenodiaminas/farmacología , Senescencia Celular/efectos de los fármacos , Platino (Metal)/química , Platino (Metal)/farmacología , Aluminio/química , Aluminio/farmacología , Animales , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/uso terapéutico , Ratones , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/químicaRESUMEN
The indiscriminate discharge of micropollutants (e.g., dyes, antibiotics, industrial additives, etc.) represents a significant risk to human health, and the removal of these substances from water bodies has become a prominent area of research within the field of environmental remediation. A simple hydrothermal-precipitation-photoreduction method was employed to synthesize novel Z-scheme heterojunction photocatalysts of AgBr/CoWO4/Ag. The catalysts demonstrated remarkable degradation capabilities with regard to a range of micropollutants present in wastewater. Of the catalysts tested, 5AgBr/CoWO4/Ag exhibited the highest degradation rates, reaching 98.58% for Rhodamine B, 86.82% for tetracycline hydrochloride, and 95.60% for 2-mercaptobenzothiazole within 60 min. In particular, the reaction kinetic rate of 5AgBr/CoWO4/Ag towards Rhodamine B degradation (k2 = 0.26278 L mg-1·min-1) is 9 times that of AgBr (k2 = 0.02953 L mg-1·min-1) and 113 times that of CoWO4 (k2 = 0.00233 L mg-1·min-1), which serves to highlight the exceptional photocatalytic activity of the material. The experimental data and subsequent analysis indicated that the enhanced photocatalytic performance can be attributed to two factors: firstly, the electron mediation by Ag nanoparticles leading to improved charge separation efficiency, and secondly, the formation of Z-scheme heterojunctions between AgBr and CoWO4. The cyclic tests provided confirmation of the excellent stability and recyclability of the AgBr/CoWO4/Ag photocatalysts. It is anticipated that this study will facilitate the development of novel methods for the degradation of refractory micropollutants and provide insights into environmental remediation, thereby contributing to the sustainable development of society.
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Nexus approach provides an effective perspective for implementing synergetic management of water resources. In this study, an interval two-stage chance-constrained water rights trading planning model under water-ecology-food nexus perspective (ITCWR-WEF) is proposed to analyze the interaction between water trading and water-ecology-food (WEF) nexus, which fills in the water resources management gaps from a novel nexus perspective. ITCWR-WEF incorporates hydrological simulation with soil and water assessment tool (SWAT), water rights configuration with interval two-stage chance-constrained programming (ITCP), and multi-criterion analysis with Technique for Order Preference by Similarity to an Ideal Solution (TOPSIS). The developed ITCWR-WEF is applied to a real case of Daguhe watershed, which has characteristics of water scarcity, food producing areas and fragile ecosystem. Initial water rights allocation is addressed before the trading. Mechanisms analysis is designed to reveal mutual effect of water rights trading and WEF nexus. Optimal water management scenario is identified through multi-criterion analysis. Results reveal that the mechanism of water rights trading with WEF nexus under low constraint-violation risk level of water availability and environment capacity is recommended to promote the rational water resources allocation to balance the economic goals, water environment and water supply security, as well as ecological and food water demand guarantees.
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Conservación de los Recursos Hídricos , Recursos Hídricos , Abastecimiento de Agua , Recursos Hídricos/provisión & distribución , Abastecimiento de Agua/estadística & datos numéricos , Conservación de los Recursos Hídricos/métodos , Conservación de los Recursos Hídricos/estadística & datos numéricos , Agricultura/métodos , Agricultura/estadística & datos numéricosRESUMEN
BACKGROUND: Evidence indicates that the Sport Education Model (SEM) has demonstrated effectiveness in enhancing students' athletic capabilities and fostering their enthusiasm for sports. Nevertheless, there remains a dearth of comprehensive reviews examining the impact of the SEM on students' attitudes toward physical education learning. PURPOSE: The purpose of this review is to elucidate the influence of the SEM on students' attitudes toward physical education learning. METHODS: Employing the preferred reporting items of the Systematic Review and Meta-analysis (PRISMA) statement guidelines, a systematic search of PubMed, SCOPUS, EBSCOhost (SPORTDiscus and CINAHL Plus), and Web of Science databases was conducted in mid-January 2023. A set of keywords associated with the SEM, attitudes toward physical education learning, and students were employed to identify relevant studies. Out of 477 studies, only 13 articles fulfilled all the eligibility criteria and were consequently incorporated into this systematic review. The validated checklist of Downs and Black (1998) was employed for the assessment, and the included studies achieved quality scores ranging from 11 to 13. The ROBINS-I tool was utilized to evaluate the risk of bias in the literature, whereby only one paper exhibited a moderate risk of bias, while the remainder were deemed to have a high risk. RESULTS: The findings unveiled significant disparities in cognitive aspects (n = 8) and affective components (n = 12) between the SEM intervention and the Traditional Teaching (TT) comparison. Existing evidence suggests that the majority of scholars concur that the SEM yields significantly superior effects in terms of students' affective and cognitive aspects compared to the TT. CONCLUSIONS: Nonetheless, several issues persist, including a lack of data regarding junior high school students and gender differences, insufficient frequency of weekly interventions, inadequate control of inter-group atmosphere disparities resulting from the same teaching setting, lack of reasonable testing, model fidelity check and consideration for regulating variables, of course, learning content, and unsuitable tools for measuring learning attitudes. In contrast, the SEM proves more effective than the TT in enhancing students' attitudes toward physical learning. SYSTEMATIC REVIEW REGISTRATION: ( https://inplasy.com/ ) (INPLASY2022100040).
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Educación y Entrenamiento Físico , Humanos , Deportes/psicología , Estudiantes/psicología , Modelos Educacionales , Actitud , AprendizajeRESUMEN
Phototheranostics have emerged as a promising subset of cancer theranostics owing to their potential to provide precise photoinduced diagnoses and therapeutic outcomes. However, the design of phototheranostics remains challenging due to the nature of tumors and their microenvironment, including limitations to the oxygen supply, high rates of recurrence and metastasis, and the immunosuppressive state of cancer cells. Here we report a dual-functional oxygen-independent phototheranostic agent, Ni-2, rationally designed to provide a near-infrared (NIR) photoactivated thermal- and hydroxyl radical (â¢OH)-enhanced photoimmunotherapeutic anticancer response. Under 880 nm laser irradiation, Ni-2 exhibited high photostability and excellent photoacoustic and photothermal effects with a photothermal conversion efficacy of 58.0%, as well as novel photoredox features that allowed the catalytic conversion of H2O2 to â¢OH upon photooxidation of Ni(II) to Ni(III). As a multifunctional photoagent, Ni-2 was found not only to inhibit tumor growth in a CT26 tumor-bearing mouse model but also to activate an immune response via a combination of photothermal- and H2O2-induced effects. When combined with an antiprogrammed death-ligand 1 (aPD-L1), Ni-2 treatment allowed for the suppression of distant tumor growth and cancer metastasis. Collectively, the present results provide support for the proposition that Ni-2 or its analogues could emerge as useful tools for photoimmunotherapy. They also highlight the potential of appropriately designed 3d transition metal complexes as "all- in-one" phototheranostics.
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Nanopartículas , Neoplasias , Ratones , Animales , Níquel , Peróxido de Hidrógeno , Nanomedicina Teranóstica/métodos , Fototerapia/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Oxígeno , Inmunoterapia , Línea Celular Tumoral , Microambiente TumoralRESUMEN
BACKGROUND: Patients undergoing prostate biopsies (PBs) suffer from low positive rates and potential risk for complications. This study aimed to develop and validate an ultrasound (US)-based radiomics score for pre-biopsy prediction of prostate cancer (PCa) and subsequently reduce unnecessary PBs. METHODS: Between December 2015 and March 2018, 196 patients undergoing initial transrectal ultrasound (TRUS)-guided PBs were retrospectively enrolled and randomly assigned to the training or validation cohort at a ratio of 7:3. A total of 1044 radiomics features were extracted from grayscale US images of each prostate nodule. After feature selection through the least absolute shrinkage and selection operator (LASSO) regression model, the radiomics score was developed from the training cohort. The prediction nomograms were developed using multivariate logistic regression analysis based on the radiomics score and clinical risk factors. The performance of the nomograms was assessed and compared in terms of discrimination, calibration, and clinical usefulness. RESULTS: The radiomics score consisted of five selected features. Multivariate logistic regression analysis demonstrated that the radiomics score, age, total prostate-specific antigen (tPSA), and prostate volume were independent factors for prediction of PCa (all p < 0.05). The integrated nomogram incorporating the radiomics score and three clinical risk factors reached an area under the curve (AUC) of 0.835 (95% confidence interval [CI], 0.729-0.941), thereby outperforming the clinical nomogram which based on only clinical factors and yielded an AUC of 0.752 (95% CI, 0.618-0.886) (p = 0.04). Both nomograms showed good calibration. Decision curve analysis indicated that using the integrated nomogram would add more benefit than using the clinical nomogram. CONCLUSION: The radiomics score was an independent factor for pre-biopsy prediction of PCa. Addition of the radiomics score to the clinical nomogram shows incremental prognostic value and may help clinicians make precise decisions to reduce unnecessary PBs.
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Neoplasias de la Próstata , Humanos , Masculino , Estudios Retrospectivos , Neoplasias de la Próstata/diagnóstico por imagenRESUMEN
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive polyarthritis that leads to cartilage and bone damage. Pre-clinical RA is a prolonged state before clinical arthritis and RA develop, in which autoantibodies (antibodies against citrullinated proteins, rheumatoid factors) can be present due to the breakdown of immunologic self-tolerance. As early treatment initiation before the onset of polyarthritis may achieve sustained remission, optimize clinical outcomes, and even prevent RA progression, the pre-clinical RA stage is showing the prospect to be the window of opportunity for RA treatment. Growing evidence has shown the role of the gut microbiota in inducing systemic inflammation and polyarthritis via multiple mechanisms, which may involve molecular mimicry, impaired intestinal barrier function, gut microbiota-derived metabolites mediated immune regulation, modulation of the gut microbiota's effect on immune cells, intestinal epithelial cells autophagy, and the interaction between the microbiome and human leukocyte antigen alleles as well as microRNAs. Since gut microbiota alterations in pre-clinical RA have been reported, potential therapies for modifying the gut microbiota in pre-clinical RA, including natural products, antibiotic therapy, fecal microbiota transplantation, probiotics, microRNAs therapy, vitamin D supplementation, autophagy inducer-based treatment, prebiotics, and diet, holds great promise for the successful treatment and even prevention of RA via altering ongoing inflammation. In this review, we summarized current studies that include pathogenesis of gut microbiota in RA progression and promising therapeutic strategies to provide novel ideas for the management of pre-clinical RA and possibly preventing arthritis progression.
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Artritis Reumatoide , Enfermedades Autoinmunes , Microbioma Gastrointestinal , MicroARNs , Humanos , InflamaciónRESUMEN
BACKGROUND: Primary retroperitoneal mucinous cystic tumours with borderline malignancy (PRMC-BM) are rare and difficult to diagnose preoperatively. We are the first to report two cases of PRMC-BM which mimic a duplex kidney and evaluate the outcomes of different surgical procedures. CASE PRESENTATION: We describe two cases of retroperitoneal cystic tumours. Both were diagnosed with duplex kidney with hydronephrosis on computed tomography scan. The first patient underwent robot-assisted laparoscopic surgery and was found to have a retroperitoneal cystic tumour. The other patient underwent an ultrasound-guided puncture before surgery and was diagnosed with retroperitoneal lymphangioma. Retroperitoneal cystectomy was performed using an open transperitoneal procedure. The final pathologic diagnosis in both cases implies PRMC-BM. The open surgical approach was associated with a shorter operation time, less intraoperative blood loss, and protected cyst wall integrity by comparing the different surgical approaches. During follow-up, the patient in the first case had tumour recurrence six months post-surgery, and the other patient was healthy without recurrence or metastasis 12 months post-surgery. CONCLUSIONS: Primary retroperitoneal mucinous cystic tumours with borderline malignancy can be enclosed within the kidney and misdiagnosed as other cystic diseases of the urinary system. Thus, an open surgical approach may be more suitable for this type of tumour.
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Quistes , Hidronefrosis , Neoplasias Retroperitoneales , Humanos , Recurrencia Local de Neoplasia , RiñónRESUMEN
To elucidate the protective mechanism of lobetyolin on oxygen-glucose deprivation/reperfusion (OGD/R)-induced damage in BV2 microglial cells. The OGD/R model was established using a chemical modeling method to simulate in vivo brain ischemia in lobetyolin-pretreated BV2 cells. The optimum lobetyolin dosage, chemical concentration, and OGD/R modeling duration were screened. The changes in cell morphology were observed, and the levels of immune response-related factors, including tumor necrosis factor-α (TNF-α), interleukin-6, inducible nitric oxide synthase (iNOS), and cluster of differentiation (CD)206, were detected using the enzyme-linked immunosorbent assay. The expression of chemokine-like-factor-1 (CKLF1), hypoxia-inducible factor (HIF)-1α, TNF-α, and CD206, was detected using western blotting. The gene expression of M1 and M2 BV2 phenotype markers was assessed using quantitative polymerase chain reaction (qPCR). The localization of M1 and M2 BV2 markers was detected using immunofluorescence analysis. The results showed that lobetyolin could protect BV2 cells from OGD/R-induced damage. After OGD/R, CKLF1/C-C chemokine receptor type 4 (CCR4) levels increased in BV2 cells, whereas the CKLF1/CCR4 level was decreased due to lobetyolin pretreatment. Additionally, BV2 cells injured with OGD/R tended to be M1 type, but lobetyolin treatment shifted the phenotype of BV2 cells from M1 type to M2 type. Lobetyolin decreased the expression of TNF-α and HIF-1α but increased the expression of transforming growth factor-ß (TGF-ß) in BV2 cells, indicating a dose-effect relationship. The qPCR results showed that lobetyolin decreased the expression of CD16, CD32, and iNOS at the gene level and increased the expression of C-C-chemokine ligand-22 and TGF-ß. The immunofluorescence analysis showed that lobetyolin decreased CD16/CD32 levels and increased CD206 levels. Lobetyolin can protect BV2 cells from OGD/R-induced damage by regulating the phenotypic polarization of BV2 and decreasing inflammatory responses. Additionally, CKLF1/CCR4 may participate in regulating lobetyolin-induced polarization of BV2 cells via the HIF-1α pathway.
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Oxígeno , Daño por Reperfusión , Humanos , Oxígeno/metabolismo , Microglía/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Glucosa/metabolismo , Fenotipo , Daño por Reperfusión/metabolismo , Quimiocinas/metabolismo , Reperfusión , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
In recent years, lanthanide (Ln) porphyrinoids have received increasing attention as theranostics. Broadly speaking, the term 'theranostics' refers to agents designed to allow both disease diagnosis and therapeutic intervention. This Review summarises the history and the 'state-of-the-art' development of Ln porphyrinoids as theranostic agents. The emphasis is on the progress made within the past decade. Applications of Ln porphyrinoids in near-infrared (NIR, 650-1700 nm) fluorescence imaging (FL), magnetic resonance imaging (MRI), radiotherapy, and chemotherapy will be discussed. The use of Ln porphyrinoids as photo-activated agents ('phototheranostics') will also be highlighted in the context of three promising strategies for regulation of porphyrinic triplet energy dissipation pathways, namely: regioisomeric effects, metal regulation, and the use of expanded porphyrinoids. The goal of this Review is to showcase some of the ongoing efforts being made to optimise Ln porphyrinoids as theranostics and as phototheranostics, in order to provide a platform for understanding likely future developments in the area, including those associated with structure-based innovations, functional improvements, and emerging biological activation strategies.
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Elementos de la Serie de los Lantanoides , Imagen por Resonancia Magnética/métodos , Medicina de Precisión , Nanomedicina Teranóstica/métodosRESUMEN
Baseflow is pivotal in maintaining catchment ecological health and improving sustainable economic development. The Yellow River Basin (YRB) is northern China's most important water supplier. However, it faces water shortage due to synergistic effects between natural conditions and anthropogenic activities. Investigating baseflow characteristics quantitively is, therefore, beneficial to promoting the sustainable development of the YRB. In this study, daily ensemble means baseflow data derived from four revised baseflow separation algorithms (i.e., the United Kingdom Institute of Hydrology (UKIH), Lyne-Hollick, Chapman-Maxwell, and Eckhardt methods) - was obtained from 2001 to 2020. Thirteen baseflow dynamics signatures were extracted to investigate baseflow spatiotemporal variations and their determinants across the YRB. The main findings were: (1) There were significant spatial distribution patterns of baseflow signatures, and most signatures had higher values in upstream and downstream reaches than in the middle reaches. There were also mixing patterns with higher values in middle and downstream reaches simultaneously. (2) The magnitude of temporal variation in baseflow signatures was most strongly correlated with catchment terrain (r = -0.4), vegetation growth (r > 0.3), and cropland coverage (r > 0.4). (3) There was a strong synergistic effect of multiple factors (e.g., soil textures, precipitation and vegetation conditions) on baseflow signature values. This study provided a heuristic evaluation of baseflow characteristics in the YRB, contributing to water resources management in the YRB and similar catchments.
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Algoritmos , Efectos Antropogénicos , Hidrología , Ríos , Agua , ChinaRESUMEN
With advances and developments in hysteroscopy, cystoscopy, transurethral resection of bladder tumor, and arthroscopy, transurethral resection of prostate (TURP) syndrome has been increasingly reported. TURP syndrome is often accompanied by severe hyponatremia, fluid overload, and a plasma hypotonic state, resulting in heart failure and pulmonary and cerebral edema. Conventional treatment methods, such as intravenous infusion of hyperosmotic saline, can rapidly reverse the downward trend of serum sodium levels in efforts to prevent and treat cerebral edema. However, this may not be suitable for patients with cardiac and renal insufficiency and may induce central pontine myelinolysis due to the possibility of worsening volume load and difficulty in controlling the correction rate of serum sodium. The patient described in this report presented with severe hyponatremia (sodium<100 mmol/L) combined with intraoperative pulmonary edema; his cardiac function and oxygenation status deteriorated after an intravenous infusion of 3% hypertonic saline. He underwent continuous renal replacement therapy (CRRT) to prevent the progression of multiple-organ edema and cardiac insufficiency. CRRT has demonstrated efficacy in the treatment of chronic hyponatremia in patients with renal failure, and can slowly and continuously correct water-electrolyte imbalance, acid-base imbalance, and volume overload. TURP syndrome with severe hyponatremia and pulmonary edema was diagnosed; accordingly, the patient was treated with 3% hypertonic saline, furosemide, and CRRT, without the development of overt neurological sequelae.
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Edema Encefálico , Terapia de Reemplazo Renal Continuo , Hiponatremia , Edema Pulmonar , Resección Transuretral de la Próstata , Masculino , Humanos , Hiponatremia/etiología , Hiponatremia/terapia , Hiponatremia/diagnóstico , Resección Transuretral de la Próstata/efectos adversos , Edema Pulmonar/etiología , Edema Encefálico/complicaciones , Terapia de Reemplazo Renal Continuo/efectos adversos , SodioRESUMEN
This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1ß, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(ß-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and ß-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1ß, IL-6, CGRP, and NO in rat serum, increased VEGF and ß-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and ß-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1ß. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing ß-EP levels.
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Isquemia Encefálica , FN-kappa B , Ratas , Masculino , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa/genética , Inhibidor NF-kappaB alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Quinasa I-kappa B/metabolismo , Quinasa I-kappa B/farmacología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/farmacología , Interleucina-6/genética , Péptido Relacionado con Gen de Calcitonina/farmacología , Ratas Sprague-Dawley , Transducción de Señal , Isquemia Encefálica/tratamiento farmacológico , ComprimidosRESUMEN
The gallium ion (Ga3+ ) has long been believed to disrupt ferric homeostasis in the body by competing with iron cofactors in metalloproteins, ultimately leading to cell death. This study revealed that through an indirect pathway, gallium can trigger ferroptosis, a type of non-apoptotic cell death regulated by iron. This is exemplified by the gallium complex of the salen ligand (Ga-1); we found that Ga-1 acts as an effective anion transporter that can affect the pH gradient and change membrane permeability, leading to mitochondrial dysfunction and the release of ferrous iron from the electron transfer chain (ETC). In addition, Ga-1 also targeted protein disulfide isomerases (PDIs) located in the endoplasmic reticulum (ER) membrane, preventing the repair of the antioxidant glutathione (GSH) system and thus enforcing ferroptosis. Finally, a combination treatment of Ga-1 and dietary polyunsaturated fatty acids (PUFAs), which enhances lipid peroxidation during ferroptosis, showed a synergistic therapeutic effect both in vitro and in vivo. This study provided us with a strategy to synergistically induce Ferroptosis in tumor cells, thereby enhancing the anti-neoplastic effect.
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Ferroptosis , Muerte Celular , Hierro/metabolismo , Peroxidación de Lípido , Antioxidantes/metabolismo , Glutatión/metabolismoRESUMEN
IgA Nephropathy (IgAN) is one of the most common causes of chronic kidney damage worldwide. Identifying new genetic factors associated with IgAN risk is of invaluable importance. To explore the association between polymorphisms of IL-23R and IL-17A and the susceptibility of IgAN, 164 IgAN patients and 192 healthy controls were genotyped for five SNPs in a Chinese Han population. A comparative analysis between genotype distributions, clinical indexes and pathological grades in the IgAN patients was also performed. The GG genotype and a G allele of rs7517847 were associated with a decreased IgAN risk (OR: 0.545; 95% CI: 0.299-0.993; p = 0.046; OR: 0.730; 95% CI: 0.541-0.984; p = 0.039) compared to the TT genotype and T allele respectively. Furthermore, the AA genotype of rs2275913 appeared to reduce the IgAN risk (OR: 0.405; 95% CI: 0.209-0.786; p = 0.007) compared to the GG genotype. Consistently, individuals harboring an AA genotype had a lower IgAN risk (OR: 0.380; 95% CI: 0.211-0.686; p = 0.001) under the recessive model. Our study demonstrated for the first time the significant associations of rs7517847 in IL-23R and rs2275913 in IL-17A with the risk of IgAN in Chinese Han.
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Glomerulonefritis por IGA , Interleucina-17/genética , Receptores de Interleucina/genética , Estudios de Casos y Controles , China , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Glomerulonefritis por IGA/genética , Humanos , Masculino , Polimorfismo de Nucleótido SimpleRESUMEN
Earth-abundant metal-based theranostics, agents that integrate diagnostic and therapeutic functions within the same molecule, may hold the key to the development of low-cost personalized medicines. Here, we report a set of O-linked nonaromatic benzitripyrrin (C^N^N^N) macrocyclic organonickel(II) complexes, Ni-1-4, containing strong σ-donating M-C bonds. Complexes Ni-1-4 are characterized by a square-planar coordination geometry as inferred from the structural studies of Ni-1. They integrate photothermal therapy, photothermal imaging, and photoacoustic imaging (PAI) within one system. This makes them attractive as potential phototheranostics. Relative to traditional Ni(II) porphyrins, such as F20TPP (tetrapentafluorophenylporphyrin), the lowest energy absorption of Ni-1 is shifted into the near infrared region, presumably as a consequence of Ni-C bonding. Ultrafast transient absorption spectroscopy combined with theoretical calculations revealed that, upon photoexcitation, a higher population of ligand-centered and 3MLCT states is seen in Ni-1 relative to NiTPBP (TPBP = 6,11,16,21-tetraphenylbenziporphyrin). Encapsulating Ni-1 in 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] (DSPE-PEG2000) afforded nanoparticles, Ni-1@DSPE, displaying red-shifted absorption features, as well as good photothermal conversion efficiency (â¼45%) in aqueous media. Proof-of-principle experiments involving thrombus treatment were carried out both in vitro and in vivo. It was found that Ni-1@DSPE in combination with 785 nm photo-irradiation for 3 min (0.3 W/cm2) proved successful in removing blood clots from a mouse thrombus model as monitored by photoacoustic imaging (PAI). The present work highlights the promise of organonickel(II) complexes as potential theranostics and the benefits that can accrue from manipulating the excited-state features of early transition-metal complexes via, for example, interrupting π-conjugation pathways.
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Complejos de Coordinación , Nanopartículas , Elementos de Transición , Animales , Complejos de Coordinación/química , Ligandos , Metales/química , Ratones , Nanopartículas/químicaRESUMEN
INTRODUCTION AND HYPOTHESIS: Surgical repair of vesicouterine fistula (VUF) can be performed through transvaginal and transabdominal routes. Transvaginal repair of VUF has been rarely reported. This study is aimed at demonstrating the feasibility and experience of transvaginal repair of VUF, and presents a step-by-step concrete surgical technique. METHODS: We presented a video of a 36-year-old woman who developed VUF after a second cesarean section. The patient underwent a transvaginal surgical repair in the prone jackknife position. We also presented the clinical data of another two patients with VUF, and summarized the experience of all three patients in whom the same technique was performed. RESULTS: The operative times of the three patients were 120, 200, and 180 min respectively. No surgical complications were observed. After a follow-up of 2-3.5 years, none of the patients had vaginal leakage. CONCLUSION: Transvaginal repair of VUF in the prone jackknife position is a feasible and effective procedure for restoring the anatomy. However, there is still a need for well-designed studies with a large number of patients to identify the most promising approach.
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Fístula , Fístula de la Vejiga Urinaria , Enfermedades Uterinas , Adulto , Cesárea/efectos adversos , Femenino , Fístula/etiología , Fístula/cirugía , Humanos , Tempo Operativo , Embarazo , Fístula de la Vejiga Urinaria/cirugía , Enfermedades Uterinas/etiología , Enfermedades Uterinas/cirugíaRESUMEN
VO2+ (3d1 ) and Cu2+ (3d9 ) are the two complementary states that usually show opposite distortions when they are doped in crystals. In this work, the optical absorption spectra (OAS), electron paramagnetic resonance (EPR) parameters, and local structure (LS) for VO2+ (and Cu2+ ) in MgNH4 PO4 ·6H2 O (MPPH) are uniformly investigated on the basis of the high-order perturbation formulas for a 3d1 (and 3d9 ) ion in tetragonally compressed (and elongated) octahedra, respectively. In the calculated formulas, the required crystal-field parameters can be obtained from the superposition model and reasonably linked with the LS distortion for VO2+ and Cu2+ centers. Based on the calculations, the tetragonal compressed [VO(H2 O)5 ]2+ cluster (and tetragonal elongated [Cu(H2 O)6 ]2+ cluster) is found to suffer tetragonal compression ratio of 1.65% and tetragonal elongation ratio of 3.8% along C4 -axis, respectively, due to the Jahn-Teller (JT) effect. The theoretical EPR parameters based on the above lattice distortions agree well with the experimental data, and the LS of the VO2+ and Cu2+ centers in MPPH is discussed.
RESUMEN
Water related problems, including water scarcity and pollution, have become increasingly urgent challenges especially in arid and semiarid regions. Two-dimensional water trading (2DWT) mechanism has been designed to unify the quantity and quality of water for relieving the water crisis. This study aims to develop a risk aversion optimization-two dimensional water trading model (RAO-2DWTM) for planning the regional-scale water resources management system (RWMS). This is the first attempt on planning RWMS through risk aversion optimization within the two-dimensional water trading framework. RAO-2DWTM cannot only support in-depth analysis regarding the effect of decision maker's preferences on system risk in different trading scenarios, but also reflect the interaction between water right trading and effluent trading, as well as disclose the optimal scheme of water resource management under uncertainties. Twenty four scenarios associated with different trading scenarios and robust levels are analyzed. The optimization scheme under the optimal risk control level is determined based on TOPSIS. Results revealed that 2DWT would bring high benefit with reduced risk cost, water deficit and emissions, implying the effectiveness of 2DWT mechanism. The results also disclosed that risk aversion behavior can mitigate water scarcity and pollution, as well as reduce risk cost, but may lead to some losses of system benefit. Consequently, decision makers should make trade-offs between system benefit and risk in identifying desired trading schemes.