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The increasing demands in optoelectronic applications have driven the advancement of organic-inorganic hybrid metal halides (OIMHs), owing to their exceptional optical and scintillation properties. Among them, zero-dimensional (0D) low-toxic manganese-based scintillators have garnered significant interest due to their exceptional optical transparency and elevated photoluminescence quantum yields (PLQYs), making them promising for colorful light-emitting diodes and X-ray imaging applications. In this study, two OIMH single crystals of (Br-PrTPP)2MnBr4 (Br-PrTPP = (3-bromopropyl) triphenylphosphonium) and (Br-BuTPP)2MnBr4 (Br-BuTPP = (4-bromobutyl) triphenylphosphonium) were prepared via a facile saturated crystallization method. Benefiting from the tetrahedrally coordinated [MnBr4]2- polyhedron, both of them exhibited strong green emissions peaked at 517 nm owing to the d-d electron transition of Mn2+ with near-unity PLQYs of 99.33 and 86.85%, respectively. Moreover, benefiting from the high optical transparencies and remarkable luminescence properties, these manganese halides also exhibit excellent radioluminescent performance with the highest light yield of up to 68,000 photons MeV-1, negligible afterglow (0.4 ms), and linear response to X-ray dose rate with the lowest detection limit of 45 nGyair s-1. In X-ray imaging, the flexible film made by the composite of (Br-PrTPP)2MnBr4 and PDMS shows an ultrahigh spatial resolution of 12.78 lp mm-1, which provides a potential visualization tool for X-ray radiography.
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Although organic-inorganic hybrid Mn2+ halides have advanced significantly, achieving high stability and narrow-band emission remains enormously challenging owing to the weak ionic nature and soft crystal lattice of the halide structure. To address these issues, we proposed a cationic engineering strategy of long-range cation π···π stacking and C-H···π interactions to simultaneously improve the crystal structural stability and rigidity. Herein, two organic zero-dimensional (0D) manganese halide hybrids of (BACQ)2MnX4 [BACQ = 4-(butylamino)-7-chloroquinolin-1-ium; X = Cl and Br] were synthesized. (BACQ)2MnX4 display strong green-light emissions with the narrowest full width at half-maximum (fwhm) of 39 nm, which is significantly smaller than those of commercial green phosphor ß-SiAlON:Eu2+ and most of reported manganese halides. Detailed Hirshfeld surface analyses demonstrate the rigid environment around the [MnX4]2- units originating from the interactions between [BACQ]+. The rigid crystal structure weakens the electron-phonon coupling and renders narrow fwhm of these manganese halides, which is further confirmed by temperature-dependent emission spectra. Remarkably, (BACQ)2MnX4 realizes outstanding structural and luminescence stabilities in various extreme environments. Benefiting from the excellent performance, these Mn2+ halides are used to assemble light-emitting diodes with a wide color gamut of 105% of the National Television System Committee 1931 standard, showcasing the advanced applications in liquid-crystal-display backlighting.
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The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger's suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50 of 0.43 nM. Further in vitro bioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivo antileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.
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Aprendizaje Profundo , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito , Simulación del Acoplamiento Molecular , Inhibidores de Proteínas Quinasas , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/antagonistas & inhibidores , Proteína Tirosina Quinasa p56(lck) Específica de Linfocito/metabolismo , Humanos , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Animales , Descubrimiento de Drogas , Antineoplásicos/farmacología , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , RatonesRESUMEN
Nitrogen is an essential nutrient and a major limiting element for the ocean ecosystem. Since the preindustrial era, substantial amounts of nitrogen from terrestrial sources have entered the ocean via rivers, groundwater, and atmospheric deposition. China serves as a key hub in the global nitrogen cycle, but the pathways, sources, and potential mitigation strategies for land-ocean nitrogen transport are unclear. By combining the CHANS, WRF-Chem, and WNF models, we estimated that 8 million tonnes (Tg) of nitrogen was transferred into the ocean in 2017 in China, with atmospheric deposition contributing 1/3. About half variation of the offshore chlorophyll concentration was explained by atmospheric deposition. The Bohai Sea was the hot spot of nitrogen input, estimated at 214 kg N ha-1, while other areas were around 25-51 kg N ha-1. The largest contributors are agricultural systems (4 Tg, 55%), followed by domestic sewage (2 Tg, 21%). Abatement measures could reduce nitrogen export to the ocean by 43%, and mitigating ammonia and nitrogen oxide emissions accounts for 33% of this reduction, highlighting the importance of addressing air pollution in resolving ocean pollution. The cost-benefit analysis suggests the priority of nitrogen reduction in cropland and transport systems for the ocean environment.
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Contaminación del Aire , Ecosistema , Nitrógeno/análisis , Ambiente , Contaminación Ambiental/análisis , Contaminación del Aire/análisis , China , Monitoreo del AmbienteRESUMEN
Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 µM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg-1·d-1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.
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Lesión Renal Aguda , Ferroptosis , Ratones Endogámicos C57BL , Fenilendiaminas , Animales , Ferroptosis/efectos de los fármacos , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Ratones , Masculino , Fenilendiaminas/farmacología , Fenilendiaminas/uso terapéutico , Ciclohexilaminas/farmacología , Ciclohexilaminas/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismoRESUMEN
Intensive anthropogenic activities have led to drastic changes in land use/land cover (LULC) and impacted the carbon storage in high-groundwater coal basins. In this paper, we conduct a case study on the Yanzhou Coalfield in Shandong Province of China. We further classify waterbodies by using the Google Earth Engine (GEE) to better investigate the process of LULC transformation and the forces driving it in four periods from 1985 to 2020 (i.e., 1985-1995, 1995-2005, 2005-2015, and 2015-2020). We modeled the spatiotemporal dynamics of carbon storage by using InVEST based on the transformation in LULC and its drivers, including mining (M), reclamation (R), urbanization and village relocation (U), and ecological restoration (E). The results indicate that carbon storage had depleted by 19.69 % (321099.06 Mg) owing to intensive transformations in LULC. The area of cropland shrank with the expansion of built-up land and waterbodies, and 56.31 % of the study area underwent transitions in land use in the study period. U was the primary driver of carbon loss while E was the leading driver of carbon gain. While the direct impact of M on carbon loss accounted for only 5.23 % of the total, it affected urbanization and led to village relocation. R led to the recovery of cropland and the reclamation of water for aquaculture, which in turn improved the efficiency of land use. However, it contributed only 2.09 % to the total increase in carbon storage. Numerous complicated and intertwined processes (211) drove the changes in carbon storage in the study area. The work here provides valuable information for decision-makers as well as people involved in reclamation and ecological restoration to better understand the link between carbon storage and the forces influencing it. The results can be used to integrate the goals of carbon sequestration into measures for land management.
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Minas de Carbón , Agua Subterránea , Humanos , Carbono , China , Carbón Mineral , Ecosistema , Conservación de los Recursos NaturalesRESUMEN
BACKGROUND: Studies have shown that fine particulate matter (PM2.5) remains a significant problem in developing countries and plays a critical role in the onset and progression of respiratory illnesses. Circular RNAs (circRNAs) are involved in many pathophysiological processes,but their relationship to PM2.5 pollution is largely unexplored. OBJECTIVES: To elucidate the functional role of hsa_circ_0000992 in PM2.5-induced inflammation in a human bronchial epithelial cell line (16HBE) and to clarify whether the competing endogenous RNA (ceRNA) mechanism is involved in the interrelationships between hsa_circ_0000992 and hsa-miR-936 and the inflammatory signaling pathways. METHODS: Detection of inflammatory factors in 16HBE cells exposed to PM2.5 by RT-qPCR and ELISA.High throughput sequencing and bioinformatics analysis methods were used to screen circRNA.The bioinformatics analysis method western blotting and dual-luciferase reporter gene system were used to verify mechanisms associated with circRNA. RESULTS: PM2.5 cause inflammation in the 16HBE cells. High throughput sequencing and RT-qPCR result revealed that the expression of hsa_circ_0000992 was markedly up-regulated in 16HBE exposed to PM2.5. The binding sites between hsa_circ_0000992 and hsa-miR-936 was confirmed by dual-luciferase reporter gene system.Western blotting and RT-qPCR showed that hsa_circ_0000992 can interact with hsa-miR-936 to regulate AKT serine/threonine kinase 3(AKT3),thereby activating the PI3K/AKT pathway and ultimately promoting the expression of interleukin (IL)- 1ß and IL-8. CONCLUSION: PM2.5 can induce the inflammatory response in 16HBE cells by activating the PI3K/AKT pathway. The expression of hsa_circ_0000992 increased when PM2.5 stimulated 16HBE cells,and the circRNA could then regulate the inflammatory response.Hsa_circ_0000992 regulates the hsa-miR-936/AKT3 axis through the ceRNA mechanism,thereby activating the PI3K/AKT signaling pathway,increasing the expression of cellular inflammatory factors,and promoting PM2.5-induced respiratory inflammation.
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MicroARNs , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Células Epiteliales/metabolismo , Material Particulado/toxicidad , Inflamación/inducido químicamente , Inflamación/genética , LuciferasasRESUMEN
We assess the associations between personality traits and co-occurrence of depressive symptoms and high BMI from adolescence to early adulthood. We employed a nationally representative cohort in China from 2010 to 2020 year. We included adolescents aged 10-19 years without depressive symptoms and unhealthy weight status (obesity, overweight, or thinness) at baseline and excluded those without any measurement of depressive symptoms or BMI at follow-ups. We assessed baseline personality traits in 7 dimensions of conscientiousness, openness, neuroticism, agreeableness, extraversion, self-esteem, and responsibility. We also assessed the combined effects of these 7 dimensions of personality traits by generating individual-level personality trait risk scores based on the weighted sum of all these 7 dimensions of personality traits. We measured the co-occurrence of depressive symptoms and high BMI using both a single measurement of depressive symptoms and BMI at the last follow-up and repeated measurements of them over 10 years. We used the multinomial logistic regression models to examine the exposure-outcome associations. At baseline, we included 1778 individuals (mean age: 14.4 year; female: 853 (48.0%)). At follow-ups, we observed increased risk of co-occurrence of depressive symptoms and high BMI per 1-SD increase in neuroticism score (1.95-2.38 odds ratio) or 1-SD decrease in self-esteem and conscientiousness (0.63-0.80 odds ratio; all P values < 0.05); we observed no evidence of associations between openness, agreeableness, extraversion, or responsibility and the risk of co-occurrence of depressive symptoms and high BMI (all P values > 0.05). For the combined effects of the 7 dimensions of personality traits, we found an elevated risk of co-occurrence of depressive symptoms and high BMI per 1-SD increase in the personality trait risk scores (OR (95% CI), single measurement at the last follow-up: 2.01, 1.66 to 2.43; trajectory classification using the repeated measurements 2.30, 1.55 to 3.42; average level using the repeated measurements: 2.27, 1.93 to 2.67). In this national cohort in China, personality traits were found to be associated with the co-occurrence of depressive symptoms and high BMI from adolescence to early adulthood. These findings highlight the importance of stratifying individuals based on their personality traits and providing targeted interventions for those at risk of comorbid depression and obesity.
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BACKGROUND AND OBJECTIVES: To evaluate the potential benefits of Bacteroides fragilis 839 (BF839), a next-generation probiotics, in reducing myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patient. METHODS AND STUDY DESIGN: 40 women with early breast cancer were randomly assigned to the BF839 (n=20) or placebo (n=20) during the administration of adjuvant chemotherapy (4 cycles of epirubicin 100mg/m2 and cyclophosphamide 600mg/m2). Myelosuppression and gastrointestinal adverse effects were monitored in both groups. RESULTS: Throughout the four treatment cycles, the percentage of patients experiencing myelosuppression was 42.5% in the BF839 group, significantly lower than the 66.3% observed in the control group (p=0.003). Two patients in the BF839 group and three patients in the placebo group received recombinant human granulocyte colony-stimulating factor (rhG-CSF) due to leuko-penia/neutropenia. When considering an ITT analysis, which included all patients regardless of rhG-CSF treatment, the BF839 group exhibited less reduction from baseline in white blood cells (-0.31±1.19 vs -1.15±0.77, p=0.012) and neutrophils (0.06±1.00 vs -0.84±0.85, p=0.004) compared to the placebo group. The difference became even more significant when excluding the patients who received rhG-CSF injections. Throughout the four treatment cycles, compared to the placebo group, the BF839 group had significantly lower rates of 3-4 grade nausea (35.0% vs 71.3%, p=0.001), vomiting (20.0% vs 45.0%, p=0.001), and diarrhea (15.0% vs 30.0%, p=0.023). CONCLUSIONS: These findings suggest that BF839 has the potential to effectively mitigate myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patients.
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Antineoplásicos , Neoplasias de la Mama , Femenino , Humanos , Antineoplásicos/efectos adversos , Bacteroides fragilis , Neoplasias de la Mama/tratamiento farmacológico , Ciclofosfamida/efectos adversos , Epirrubicina/efectos adversos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Proteínas Recombinantes/uso terapéuticoRESUMEN
Zero-dimensional (0D) hybrid metal halides have been emerged as room-temperature phosphorescence (RTP) materials, but synchronous optimization of multiple phosphorescence performance in one structural platform remains less resolved, and stable RTP activity in aqueous medium is also unrealized due to serious instability toward water and oxygen. Herein, we demonstrated a photophysical tuning strategy in a new 0D hybrid zinc halide family of (BTPP)2ZnX4 (BTPP = benzyltriphenylphosphonium, X = Cl and Br). Infrequently, the delicate combination of organic and inorganic species enables this family to display multiple ultralong green afterglow and efficient self-trapped exciton (STE) associated cyan phosphorescence. Compared with inert luminescence of [BTPP]+ cation, incorporation of anionic [ZnX4]2- effectively enhance the spin-orbit coupling effect, which significantly boosts the photoluminescence quantum yield (PLQY) up to 30.66% and 54.62% for afterglow and phosphorescence, respectively. Synchronously, the corresponding luminescence lifetime extend to 143.94 ms and 0.308 µs surpassing the indiscernible phosphorescence of [BTPP]X salt. More importantly, this halide family presents robust RTP emission with nearly unattenuated PLQY in water and harsh condition (acid and basic aqueous solution) over half a year. The highly efficient integrated afterglow and STE phosphorescence as well as ultrahigh aqueous state RTP realize multiple anti-counterfeiting applications in wide chemical environments.
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OBJECTIVE: Exploring the clinical efficacy, safety, and surgical techniques of two-way rendezvous and trenching method for transurethral holmium laser prostatectomy in the treatment of benign prostatic hyperplasia. METHODS: Retrospective analysis of clinical data on preoperative, intraoperative, and postoperative follow-up of 326 patients with benign prostatic hyperplasia who underwent two-way rendezvous and trenching method of transurethral holmium laser prostatectomy at the Urology Department of Wujin People's Hospital in Changzhou City from January 2020 to January 2023. RESULTS: Compared with preoperative measures, IPSS symptom score, quality of life (QoL) score, maximum urinary flow rate (Qmax), and residual urine volume (PVR) were significantly improved at 1, 6, and 12 months postoperatively (P<0.05). Thirty two patients with normal and regular sexual life pre-operation were observed. There were no significant changes in their IIEF-5 score and Erectile Hardness Scale (EHGS) score after surgery compared with pre-operation (P<0.05). There were 9 patients (28.12%) with retrograde ejaculation after surgery. CONCLUSION: The two-way rendezvous and trenching method of transurethral holmium laser prostatectomy is a safe and effective method for treating benign prostatic hyperplasia, with precise results, high safety, minimal trauma, and fast postoperative recovery.
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Terapia por Láser , Láseres de Estado Sólido , Hiperplasia Prostática , Resección Transuretral de la Próstata , Masculino , Humanos , Próstata , Hiperplasia Prostática/diagnóstico , Calidad de Vida , Láseres de Estado Sólido/uso terapéutico , Estudios Retrospectivos , Resección Transuretral de la Próstata/métodos , Resultado del Tratamiento , Terapia por Láser/métodos , HolmioRESUMEN
OBJECTIVE: Comparison of clinical efficacy between transurethral holmium laser prostate enucleation (two-way rendezvous and trenching method) and transurethral plasma enucleation. METHODS: A total of 483 patients with benign prostatic hyperplasia who were admitted to our hospital from December 2019 to December 2022 were randomly divided into an observation group (245 cases) and a control group (238 cases) using a random number table method. The observation group underwent transurethral holmium laser prostatectomy, while the control group underwent transurethral plasma prostatectomy,evaluate the efficacy of two surgical methods. RESULT: The IPSS symptom score, quality of life (QOL) score, maximum urinary flow rate (Qmax), residual urine volume (PVR) and other indicators were significantly improved in both groups after 6 months of surgery compared to before (P<0.05), and there was no statistically significant difference between the two groups (P>0.05). The incidence of postoperative complications in the observation group was significantly lower than that in the control group (P<0.05). There was no statistically significant difference in sexual function and retrograde ejaculation between the two groups of patients(P>0.05). CONCLUSION: Both surgical methods have good surgical efficacy, but compared with prostate plasma resection, holmium laser prostatectomy can reduce intraoperative bleeding in patients with BPH, effectively shorten catheter retention time, patient hospitalization time, and postoperative bladder flushing time, resulting in higher quality of life and safety.
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Terapia por Láser , Láseres de Estado Sólido , Hiperplasia Prostática , Resección Transuretral de la Próstata , Masculino , Humanos , Hiperplasia Prostática/complicaciones , Calidad de Vida , Láseres de Estado Sólido/uso terapéutico , Resección Transuretral de la Próstata/métodos , Próstata/cirugía , Terapia por Láser/métodos , Resultado del Tratamiento , HolmioRESUMEN
Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males. However, the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood, especially in teleosts. In this study, cyp17a1-/- zebrafish ( Danio rerio) exhibited excessive visceral adipose tissue (VAT), lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis (DNL) enzymes. The assay for transposase accessible chromatin with sequencing (ATAC-seq) results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/- fish compared to cyp17a1+/+ male fish, including stearoyl-CoA desaturase ( scd) and fatty acid synthase ( fasn). Androgen response element (ARE) motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+ male fish but not in cyp17a1-/- fish. Both androgen receptor ( ar)-/- and wild-type (WT) zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue, lipid content, and up-regulated expression and activity of hepatic de novo lipogenesis enzymes. The Ar agonist BMS-564929 reduced the content of VAT and lipid content, and down-regulated acetyl-CoA carboxylase a ( acaca), fasn, and scd expression. Mechanistically, the rescue effect of testosterone on cyp17a1-/- fish in terms of phenotypes was abolished when ar was additionally depleted. Collectively, these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish, thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.
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Andrógenos , Lipogénesis , Masculino , Animales , Andrógenos/farmacología , Lipogénesis/genética , Pez Cebra/genética , Testosterona , Lípidos , Transducción de Señal , CromatinaRESUMEN
Numerous guidelines have called for personalized interventions to address childhood obesity. The role of fat mass and obesity-associated gene (FTO) in the risk of childhood obesity has been summarized. However, it remains unclear whether FTO could influence individual responses to obesity interventions, especially in children. To address this, we systematically reviewed 12,255 records across 10 databases/registers and included 13 lifestyle-based obesity interventions (3980 children with overweight/obesity) reporting changes in body mass index (BMI) Z-score, BMI, waist circumference, waist-to-hip ratio, and body fat percentage after interventions. These obesity-related outcomes were first compared between children carrying different FTO genotypes (rs9939609 or its proxy) and then synthesized by random-effect meta-analysis models. The results from single-group interventions showed no evidence of associations between FTO risk allele and changes in obesity-related outcomes after interventions (e.g., BMI Z-score: -0.01; 95% CI: -0.04, 0.01). The results from controlled trials showed that associations between the FTO risk allele and changes in obesity-related outcomes did not differ by intervention/control group. To conclude, the FTO risk allele might play a minor role in the response to obesity interventions among children. Future studies might pay more attention to the accumulation effect of multiple genes in the intervention process among children.
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Obesidad Infantil , Niño , Humanos , Índice de Masa Corporal , Predisposición Genética a la Enfermedad , Genotipo , Obesidad Infantil/genética , Obesidad Infantil/prevención & control , Pérdida de PesoRESUMEN
BACKGROUND: Primary central nervous system lymphoma (PCNSL) is an aggressive lymphoma that primarily affects the central nervous system. Current treatments, such as surgery, chemotherapy, and whole-brain radiotherapy, often fail to achieve satisfactory results. The prognosis for patients with refractory or relapsed (R/R) PCNSL is bleak. The optimal treatment for refractory or relapsed PCNSL is poorly defined due to a limited number of studies in this setting. Bruton's tyrosine kinase (BTK) inhibitors, as part of targeted therapy regimens, have undergone testing in several clinical trials against PCNSL and have shown promising results in the treatment of R/R PCNSL. In this meta-analysis, we aim to explore and critically appraise the evidence regarding the efficacy of BTK inhibitors in the treatment of refractory or relapsed PCNSL. METHODS: A systematic search was conducted on multiple databases including PubMed, Embase, Cochrane library, Wanfang Data Knowledge Service Platform, and CNKI, covering the period up to November 2023. The inclusion criteria for studies were patients with R/R PCNSL who received BTK inhibitors, and reported data on overall response rate (ORR) and complete remission (CR). The pooled rates were calculated using a random-effects or fixed-effects model with a double arcsine transformation, and 95% CIs were determined for all outcomes. RESULTS: In total, 1 studies involving 185 patients were identified and included in the meta-analysis. The pooled complete remission (CR) rate of BTK inhibitors-based treatment for R/R PCNSL was found to be 50%. Subgroup analysis revealed that the CR rates for BTK inhibitor monotherapy, BTK inhibitor combined with chemotherapy, and BTK inhibitor combined with radiotherapy for R/R PCNSL were 7%, 68%, and 80%, respectively. The ORR for BTK inhibitors-based treatment for R/R PCNSL was 70%. Subgroup analysis showed that the ORR rates for BTK inhibitor monotherapy and BTK inhibitor combined with chemotherapy for R/R PCNSL were 55% and 83%, respectively. The most common adverse events (AEs) reported were hematologic AEs, including neutropenia, anemia, and thrombocytopenia. Severe nonhematologic AEs included rash, febrile neutropenia, increased levels of aspartate aminotransferase, and increased blood bilirubin. CONCLUSIONS: BTK inhibitors can be regarded as a safe and effective treatment option for R/R PCNSL, thereby providing a potential new avenue for R/R PCNSL treatment. However, it is important to note that further large-sample prospective randomized controlled trials are needed to validate these findings and establish their wider applicability.
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Agammaglobulinemia Tirosina Quinasa , Neoplasias del Sistema Nervioso Central , Recurrencia Local de Neoplasia , Inhibidores de Proteínas Quinasas , Humanos , Agammaglobulinemia Tirosina Quinasa/antagonistas & inhibidores , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Linfoma/tratamiento farmacológicoRESUMEN
Considering the instability and toxicity of 3D Pb-based perovskite nanocrystals, lead-free low-dimensional organic-inorganic hybrid metal halides have attracted widespread attention as potential substitutes. Herein, two new tin-based 0D halides [H4BAPP]SnBr5·Br and [H4BAPP]SnCl5·Cl·H2O (BAPP = 1,4-bis(3-aminopropyl)piperazine) were synthesized successfully based on [SnX5]3- as an emission center. Typically, [H4BAPP]SnBr5·Br and [H4BAPP]SnCl5·Cl·H2O display broadband yellow and yellow-green light emissions originating from the radiative recombination of self-trapped excitons (STEs). The photoluminescence quantum yields (PLQYs) of the two compounds were calculated to be 19.27% and 2.36%, respectively. Furthermore, the excellent chemical and thermal stability and broadband light emissions reveal their potential application in solid-state white lighting diodes.
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Environmentally friendly and highly efficient blue luminescent materials are an unremitting pursuit in the optoelectronic field. Herein, we assembled a new 0D lead-free metal halide of (F-PPA)ZnBr4, which exhibits narrow blue light emission with a remarkable PLQY of 50.15%, high stability and high detection sensitivity toward UV light. These results indicate the potential for the application of low-dimensional zinc-based halides in multiple optoelectronic devices.
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Excessive induction of inflammatory and immune responses is widely considered as one of vital factors contributing to the pathogenesis and progression of central nervous system (CNS) diseases. Neutrophils are well-studied members of inflammatory and immune cell family, contributing to the innate and adaptive immunity. Neutrophil-released neutrophil extracellular traps (NETs) play an important role in the regulation of various kinds of diseases, including CNS diseases. In this review, current knowledge on the biological features of NETs will be introduced. In addition, the role of NETs in several popular and well-studied CNS diseases including cerebral stroke, Alzheimer's disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and neurological cancers will be described and discussed through the reviewing of previous related studies.
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Enfermedades del Sistema Nervioso Central , Trampas Extracelulares , Esclerosis Múltiple , Humanos , Sistema Nervioso Central , NeutrófilosRESUMEN
A quantitative water detection method is urgently needed in storage facilities, space exploration, and the chemical industry. Although numerous physical techniques have been widely utilized to determine the water content, they still suffer from many disadvantages such as highly expensive special instruments, complicated analysis processes, etc. Hence, a convenient, rapid, and sensitive water analysis method is highly desirable. Herein, we developed a visual fluorescence sensing technology for water detection based on reversible PL off-on switching of organic-inorganic hybrid zero-dimensional (0D) manganese halides. In this work, a family of hybrid manganese halides were synthesized through a facile solution method, namely, [NH4(18-Crown-6)]2MnBr4, [Ca(18-Crown-6)·3H2O](18-Crown-6)MnBr4, [NH4(dibenzo-18-Crown-6)]2MnBr4, and [Ca(dibenzo-18-Crown-6)·2H2O]MnBr4. Excited by UV light, these highly crystalline manganese halides exhibit strong green light emissions from the d-d electron transition of Mn2+ with near-unity photoluminescence quantum yield and submillisecond lifetime. Benefiting from the dynamic and weak ionic bonding interactions, these 0D manganese halides display reversible water-response on/off luminescence switching but fail in any other aprotic solvents. Therefore, these 0D hybrid manganese halides can be explored as ultrafast visual fluorescence probes to detect the trace amount of water in organic solvents with multiple superiorities of rapid response time (< 2 s), ultralow detection limit (9.71 ppm), excellent repeatability, etc. The reversible water-response luminescent on/off switching also provides a binary optical gate with advanced applications in anticounterfeiting and information security, etc.
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HCC, also known as hepatocellular carcinoma, is a frequently occurring form of cancer with an unfavorable prognosis. This research constructed a prognostic signature related to ubiquitination and investigated its correlation with the response to immunotherapy in HCC. The Molecular Signatures Database provided a compilation of genes associated with ubiquitination. A gene signature related to ubiquitination was obtained through Cox regression using the Least Absolute Shrinkage and Selection Operator method. The genetic factors CPY26B1, MCM10, SPINK4, and TRIM54 notably impacted the outcomes of HCC. The patients were divided into two groups: one group had a high risk of poor survival while the other had a low risk but a greater chance of controlling HCC progression. Both univariate and multivariate analyses using Cox regression found the risk score to be an independent predictor of HCC prognosis. Gene set enrichment analysis (GSEA) indicated enrichment in cell cycle and cancer-related microRNAs in high-risk groups. The tumor microenvironment (TME), response to immunotherapy, and effectiveness of chemotherapy medications positively correlated with the risk score. In the high-risk group, erlotinib showed higher IC50 values compared to the low-risk group which exhibited higher IC50 values for VX-11e, AKT inhibitor VIII, AT-7519, BMS345541, Bortezomib, CP466722, FMK, and JNK-9L. The results of RT-qPCR revealed that the expression of four UEGs was higher in tumor tissue as compared to normal tissue. Based on the genes that were expressed differently and associated with ubiquitination-related tumor categorization, we have developed a pattern of four genes and a strong nomogram that can predict the prognosis of HCC, which could be useful in identifying and managing HCC.