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Fluorescence sensing and imaging techniques are being widely studied for detecting carbon monoxide (CO) in living organisms due to their speed, sensitivity, and ease of use to biological systems. Most fluorescent probes used for this purpose are based on heavy metal ions like Pd, with a few using elements like Ru, Rh, Ir, Os, Tb, and Eu. However, these metals can be expensive and toxic to cells. There is a need for more affordable and biologically safe fluorescent probes for CO detection. Drawing inspiration from the robust affinity exhibited by heme iron toward CO, in this work, a rhodamine derivative called RBF was developed for imaging CO in living cells by binding to Fe(III) and could be used for CO sensing. A Fe(III)-based fluorescent probe for CO imaging in living cells offers advantages of cost effectiveness, low toxicity, and ease of use. The fluorescence detection using the RBF-Fe system showed a direct correlation with increasing levels of CORM-3 (LOD = 146 nM) or the exposure time of CO gas, displaying reduced fluorescence. A CO test paper based on RBF-Fe was created for simple on-site CO detection, where fluorescence would diminish in response to CO exposure, allowing rapid (2 min) visual identification. Imaging of CO in living cells was successfully conducted using the probe system, showing a decrease in fluorescence intensity as CORM-3 concentrations increased, indicating its effectiveness in monitoring CO levels accurately within living cells.
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Monóxido de Carbono , Compuestos Férricos , Colorantes Fluorescentes , Monóxido de Carbono/análisis , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Compuestos Férricos/química , Compuestos Férricos/análisis , Imagen Óptica , Rodaminas/química , Células HeLaRESUMEN
Self-assembled lipid nanoparticles (LNPs), serving as essential nanocarriers in recent COVID-19 mRNA vaccines, provide a stable and versatile platform for delivering a wide range of biological materials. Notably, LNPs with unique inverse mesostructures, such as cubosomes and hexosomes, are recognized as fusogenic nanocarriers in the drug delivery field. This study delves into the physicochemical properties, including size, lyotropic liquid crystalline mesophase, and apparent pKa of LNPs with various lipid components, consisting of two ionizable lipids (ALC-0315 and SM-102) used in commercial COVID-19 mRNA vaccines and a well-known inverse mesophase structure-forming helper lipid, phytantriol (PT). Two partial mesophase diagrams are generated for both ALC-0315/PT LNPs and SM-102/PT LNPs as a function of two factors, ionizable lipid ratio (α, 0-100 mol%) and pH condition (pH 3-11). Furthermore, the impact of different LNP stabilizers (Pluronic F127, Pluronic F108, and Tween 80) on their pH-dependent phase behavior is evaluated. The findings offer insights into the self-assembled mesostructure and ionization state of the studied LNPs with potentially enhanced endosomal escape ability. This research is relevant to developing innovative next-generation LNP systems for delivering various therapeutics.
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Alcoholes Grasos , Lípidos , Cristales Líquidos , Nanopartículas , Nanopartículas/química , Alcoholes Grasos/química , Cristales Líquidos/química , Concentración de Iones de Hidrógeno , Lípidos/química , Iones/química , LiposomasRESUMEN
OBJECTIVE: Fatty acids play a critical role in the proper functioning of the brain. This study investigated the effects of a high-fat (HF) diet on brain fatty acid profiles of offspring exposed to maternal gestational diabetes mellitus (GDM). METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish the GDM animal model. Brain fatty acid profiles of the offspring mice were measured by gas chromatography at weaning and adulthood. Protein expressions of the fatty acid transport pathway Wnt3/ß-catenin and the target protein major facilitator superfamily domain-containing 2a (MFSD2a) were measured in the offspring brain by Western blot. RESULTS: Maternal GDM increased the body weight of male offspring (P < 0.05). In weaning offspring, factorial analysis showed that maternal GDM increased the monounsaturated fatty acid (MUFA) percentage of the weaning offspring's brain (P < 0.05). Maternal GDM decreased offspring brain arachidonic acid (AA), but HF diet increased brain linoleic acid (LA) (P < 0.05). Maternal GDM and HF diet reduced offspring brain docosahexaenoic acid (DHA), and the male offspring had higher DHA than the female offspring (P < 0.05). In adult offspring, factorial analysis showed that HF diet increased brain MUFA in offspring, and male offspring had higher brain MUFA than female offspring (P < 0.05). The HF diet increased brain LA in the offspring. Male offspring had higher level of AA than female offspring (P < 0.05). HF diet reduced DHA in the brains of female offspring. The brain protein expression of ß-catenin and MFSD2a in both weaning and adult female offspring was lower in the HF + GDM group than in the CON group (P < 0.05). CONCLUSIONS: Maternal GDM increased the susceptibility of male offspring to HF diet-induced obesity. HF diet-induced adverse brain fatty acid profiles in both male and female offspring exposed to GDM.
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Encéfalo , Diabetes Gestacional , Dieta Alta en Grasa , Ácidos Grasos , Efectos Tardíos de la Exposición Prenatal , Animales , Embarazo , Femenino , Diabetes Gestacional/metabolismo , Ratones , Dieta Alta en Grasa/efectos adversos , Encéfalo/metabolismo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Masculino , Ácidos Grasos/metabolismo , Modelos Animales de Enfermedad , Fenómenos Fisiologicos Nutricionales MaternosRESUMEN
BACKGROUND: Polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA), are critical for proper fetal brain growth and development. Gestational diabetes mellitus (GDM) could affect maternal-fetal fatty acid metabolism. OBJECTIVE: This study aimed to explore the effect of GDM and high-fat (HF) diet on the DHA transport signaling pathway in the placenta-brain axis and fatty acid concentrations in the fetal brain. METHODS: Insulin receptor antagonist (S961) and HF diet were used to establish an animal model of GDM. Eighty female C57BL/6J mice were randomly divided into control (CON), GDM, HF, and HF+GDM groups. The fatty acid profiles of the maternal liver and fetal brain were analyzed by gas chromatography. In addition, we analyzed the protein amounts of maternal liver fatty acid desaturase (FADS1/3), elongase (ELOVL2/5) and the regulatory factor sterol-regulatory element-binding protein (SREBP)-1c, and the DHA transport signaling pathway (Wnt3/ß-catenin/MFSD2a) of the placenta and fetal brain using western blotting. RESULTS: GDM promoted the decrease of maternal liver ELOVL2, ELOVL5, and SREBP-1c. Accordingly, we observed a significant decrease in the amount of maternal liver arachidonic acid (AA), DHA, and total n-3 PUFA and n-6 PUFA induced by GDM. GDM also significantly decreased the amount of DHA and n-3 PUFA in the fetal brain. GDM downregulated the Wnt3/ß-catenin/MFSD2a signaling pathway, which transfers n-3 PUFA in the placenta and fetal brain. The HF diet increased n-6 PUFA amounts in the maternal liver, correspondingly increasing linoleic acid, gamma-linolenic acid, AA, and total n-6 PUFA in the fetal brain, but decreased DHA amount in the fetal brain. However, HF diet only tended to decrease placental ß-catenin and MFSD2a amounts (P = 0.074 and P = 0.098, respectively). CONCLUSIONS: Maternal GDM could affect the fatty acid profile of the fetal brain both by downregulating the Wnt3/ß-catenin/MFSD2a pathway of the placental-fetal barrier and by affecting maternal fatty acid metabolism.
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Diabetes Gestacional , Ácidos Grasos Omega-3 , Humanos , Animales , Ratones , Femenino , Embarazo , Diabetes Gestacional/metabolismo , Ácidos Grasos/metabolismo , Placenta/metabolismo , beta Catenina/metabolismo , Ratones Endogámicos C57BL , Ácidos Grasos Omega-3/metabolismo , Ácidos Grasos Insaturados/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácido Araquidónico , Encéfalo/metabolismoRESUMEN
The prevalence of cardiovascular diseases continues to be a challenge for global health, necessitating innovative solutions. The potential of high-density lipoprotein (HDL) mimetic nanotherapeutics in the context of cardiovascular disease and the intricate mechanisms underlying the interactions between monocyte-derived cells and HDL mimetic showing their impact on inflammation, cellular lipid metabolism, and the progression of atherosclerotic plaque. Preclinical studies have demonstrated that HDL mimetic nanotherapeutics can regulate monocyte recruitment and macrophage polarization towards an anti-inflammatory phenotype, suggesting their potential to impede the progression of atherosclerosis. The challenges and opportunities associated with the clinical application of HDL mimetic nanotherapeutics, emphasize the need for additional research to gain a better understanding of the precise molecular pathways and long-term effects of these nanotherapeutics on monocytes and macrophages to maximize their therapeutic efficacy. Furthermore, the use of nanotechnology in the treatment of cardiovascular diseases highlights the potential of nanoparticles for targeted treatments. Moreover, the concept of theranostics combines therapy and diagnosis to create a selective platform for the conversion of traditional therapeutic medications into specialized and customized treatments. The multifaceted contributions of HDL to cardiovascular and metabolic health via highlight its potential to improve plaque stability and avert atherosclerosis-related problems. There is a need for further research to maximize the therapeutic efficacy of HDL mimetic nanotherapeutics and to develop targeted treatment approaches to prevent atherosclerosis. This review provides a comprehensive overview of the potential of nanotherapeutics in the treatment of cardiovascular diseases, emphasizing the need for innovative solutions to address the challenges posed by cardiovascular diseases.
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Enfermedades Cardiovasculares , Lipoproteínas HDL , Macrófagos , Monocitos , Humanos , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Animales , Enfermedades Cardiovasculares/tratamiento farmacológico , Monocitos/efectos de los fármacos , Nanopartículas/química , Aterosclerosis/tratamiento farmacológico , Placa Aterosclerótica/tratamiento farmacológico , Nanomedicina/métodos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacologíaRESUMEN
Acute sleep deprivation has aroused widespread concern and the relationship between acute sleep deprivation and cortisol levels is inconsistent. This study aimed to explore additional evidence and details. The PubMed, Web of Science, EMBASE, CLINAHL and Cochrane databases were searched for eligible studies published up to June 7, 2023. All analyses were performed using Review Manager 5.4 and Stata/SE 14.0. A total of 24 studies contributed to this meta-analysis. There was no significant difference in cortisol levels between participants with acute sleep deprivation and normal sleep in 21 crossover-designed studies (SMD = 0.18; 95% CI: -0.11, 0.45; p = 0.208) or 3 RCTs (SMD = 0.26; 95% CI: -0.22, 0.73; p = 0.286). Subgroup analysis revealed that the pooled effects were significant for studies using serum as the sample (SMD = 0.46; 95%CI: 0.11, 0.81; p = 0.011). Studies reporting cortisol levels in the morning, in the afternoon and in the evening did not show significant difference (p > 0.05). The pooled effects were statistically significant for studies with multiple measurements (SMD = 0.28; 95%CI: 0.03, 0.53; p = 0.027) but not for studies with single cortisol assessments (p = 0.777). When the serum was used as the test sample, the cortisol levels of individuals after acute sleep deprivation were higher than those with normal sleep.
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Hidrocortisona , Privación de Sueño , Privación de Sueño/sangre , Hidrocortisona/sangre , HumanosRESUMEN
BACKGROUND: This meta-analysis aimed to assess the safety and efficacy of robotic-assisted natural orifice specimen extraction surgery (NOSE) compared to traditional robotic transabdominal wall specimen retrieval surgery (TWSR) for colorectal cancer. METHODS: A systematic search was conducted in three electronic databases (PubMed, Web of Science and Embase) from inception to August 2023. Primary outcomes included postoperative complications, the number of lymph nodes harvested, overall survival and disease-free survival. Secondary outcomes included the postoperative visual analog scale (VAS) score, the additional use of analgesics, the restoration of gastrointestinal function, blood loss, the mean operation time, and length of postoperative hospital stay. RESULTS: In this meta-analysis, a total of 717 patients from 6 observational studies met the inclusion criteria. Compared with the TWSR group, the NOSE group had greater benefits in terms of overall postoperative complications [odds ratios (OR) 0.55; 95% confidence intervals (CI) = 0.34 to 0.89; P = 0.01, I2 = 0%)], the number of lymph nodes harvested [weighted mean differences (WMD) = 1.18; 95% CI = 0.15 to 2.21; P = 0.02, I2 = 0%)], the rate of wound infection (OR 0.17; 95% CI = 0.04 to 0.80; P = 0.02, I2 = 0%), the passed flatus time (WMD = - 0.35 days; 95% CI = - 0.60 to - 0.10; P = 0.007, I2 = 73%), the additional use of analgesics (OR 0.25; 95% CI = 0.15 to 0.40; P < 0.001, I2 = 0%), the diet recovery time (WMD = - 0.56; 95% CI = - 1.00 to - 0.11; P = 0.01, I2 = 78%) and the postoperative VAS score (WMD = - 1.23; 95% CI = - 1.63 to - 0.83; P < 0.001, I2 = 65%). There were no significant differences in the blood loss (WMD = - 5.78 ml; 95% CI = - 17.57 to 6.00; P = 0.34, I2 = 90%), mean operation time (WMD = 14.10 min; 95% CI = - 3.76 to 31.96; P = 0.12) (I2 = 93%), length of postoperative hospital stay (WMD = - 0.47 day; 95% CI = - 0.98 to 0.03; P = 0.07, I2 = 51%), incidences of postoperative ileus (OR 1.0; 95% CI = 0.22 to 4.46; P = 1.00, I2 = 0%), anastomotic leakage (OR 0.73; 95% CI = 0.33 to 1.60; P = 0.43, I2 = 0%), and intra-abdominal abscess (OR 1.59; 95% CI = 0.47 to 5.40; P = 0.46, I2 = 0%), or 3-year overall survival [hazard ratio (HR) = 1.07, 95% CI = 0.60 to 1.94; P = 0.81)] or disease-free survival (HR = 0.94, 95% CI = 0.54 to 1.63; P = 0.82, I2 = 0%). CONCLUSION: This meta-analysis showed that the NOSE group had better postoperative outcomes than did the TWSR group and that NOSE was a safe and viable alternative to TWSR. More large-sample reviews and further randomized trials are warranted.
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Neoplasias Colorrectales , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Neoplasias Colorrectales/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Cirugía Endoscópica por Orificios Naturales/métodos , Tiempo de Internación/estadística & datos numéricos , Tempo OperativoRESUMEN
Micromechanical resonators have aroused growing interest as biological and chemical sensors, and microcantilever beams are the main research focus. Recently, a resonant microcantilever with an integrated heater has been applied in on-chip thermogravimetric analysis (TGA). However, there is a strong relationship between the mass sensitivity of a resonant microcantilever and the location of adsorbed masses. Different sampling positions will cause sensitivity differences, which will result in an inaccurate calculation of mass change. Herein, an integrated H-shaped resonant beam with uniform mass sensitivity and temperature distribution is proposed and developed to improve the accuracy of bio/chemical sensing and TGA applications. Experiments verified that the presented resonant beam possesses much better uniformity of sensitivity and temperature distribution compared with resonant microcantilevers. Gas-sensing and TGA experiments utilizing the integrated resonant beam were also carried out and exhibited good measurement accuracy.
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In the postantibiotic era, the pathogenicity and resistance of pathogens have increased, leading to an increase in intestinal inflammatory disease. Bacterial infections remain the leading cause of animal mortality. With increasing resistance to antibiotics, there has been a significant decrease in resistance to both inflammation and disease in animals, thus decreasing production efficiency and increasing production costs. These side effects have serious consequences and have detracted from the development of China's pig industry. Microcin C7 (McC7) demonstrates potent antibacterial activity against a broad spectrum of pathogens, stable physicochemical properties, and low toxicity, reducing the likelihood of resistance development. Thus, McC7 has received increasing attention as a potential clinical antibacterial and immunomodulatory agent. McC7 has the potential to serve as a new generation of antibiotic substitutes; however, its commercial applications in the livestock and poultry industry have been limited. In this review, we summarize and discuss the biosynthesis, biochemical properties, structural characteristics, mechanism of action, and immune strategies of McC7. We also describe the ability of McC7 to improve intestinal health. Our aim in this study was to provide a theoretical basis for the application of McC7 as a new feed additive or new veterinary drug in the livestock and poultry breeding industry, thus providing a new strategy for alleviating resistance through feed and mitigating drug resistance. Furthermore, this review provides insight into the new functions and anti-infection mechanisms of bacteriocin peptides and proposes crucial ideas for the research, product development, and application of bacteriocin peptides in different fields, such as the food and medical industries.
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Antibacterianos , Bacteriocinas , Bacteriocinas/farmacología , Bacteriocinas/química , Bacteriocinas/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/uso terapéutico , Animales , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/uso terapéutico , Porcinos , HumanosRESUMEN
Waterlogging stress is an important abiotic stress that adversely affects maize growth and yield. The mechanism regulating the early stage of the maize response to waterlogging stress is largely unknown. In this study, CM37 and cmh15 seedlings were treated with waterlogging stress and then examined in terms of their physiological changes. The results indicated that inbred line cmh15 is more tolerant to waterlogging stress and less susceptible to peroxide-based damages than CM37. The RNA sequencing analysis identified 1,359 down-regulated genes and 830 up-regulated genes in the waterlogging-treated cmh15 plants (relative to the corresponding control levels). According to the Gene Ontology analysis for the differentially expressed genes (DEGs), some important terms were identified which may play important roles in the response to waterlogging stress. Moreover, enriched Kyoto Encyclopedia of Genes and Genomes pathways were also identified for the DEGs. Furthermore, the substantial changes in the expression of 36 key transcription factors may be closely related to the maize in response to waterlogging stress. This study offers important insights into the mechanism in regulating maize tolerance to waterlogging stress, with important foundations for future research.
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Identifying terrain parameters is important for high-fidelity simulation and high-performance control of planetary rovers. The wheel-terrain interaction classes (WTICs) are usually different for rovers traversing various types of terrain. Every terramechanics model corresponds to its wheel-terrain interaction class (WTIC). Therefore, for terrain parameter identification of the terramechanics model when rovers traverse various terrains, terramechanics model switching corresponding to the WTIC needs to be solved. This paper proposes a speed-independent vibration-based method for WTIC recognition to switch the terramechanics model and then identify its terrain parameters. In order to switch terramechanics models, wheel-terrain interactions are divided into three classes. Three vibration models of wheels under three WTICs have been built and analyzed. Vibration features in the models are extracted and non-dimensionalized to be independent of wheel speed. A vibration-feature-based recognition method of the WTIC is proposed. Then, the terrain parameters of the terramechanics model corresponding to the recognized WTIC are identified. Experiment results obtained using a Planetary Rover Prototype show that the identification method of terrain parameters is effective for rovers traversing various terrains. The relative errors of estimated wheel-terrain interaction force with identified terrain parameters are less than 16%, 12%, and 9% for rovers traversing hard, gravel, and sandy terrain, respectively.
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Recent studies have suggested that rail transit not only facilitates urban growth but also promotes urban agglomeration. Yet research that links industrial agglomeration with rail transit is scant-what types of industries are likely to cluster near rail stations? To what extent can rail transit access be seen as having an influence on industrial agglomeration? And how do these interactions vary as rail transit proximity increases? To answer these and related questions, we investigate the relationship between industrial agglomeration and rail transit in the Dallas-Fort Worth metropolitan area using the Longitudinal Employer Dynamics (LEHD) employment data from 2014 at the census block level. First, we use the Local Indicator of Spatial Association statistics (LISA) tests to identify industrial agglomeration patterns within the study area. We then use logistics models to reveal the relationship between rail transit proximity and industrial agglomeration. Our study finds that the impacts of rail transit on industrial agglomeration, in terms of magnitudes and signs, are mixed across industries. The varying results suggest that the benefits of rail transit access exhibit considerable demand from certain industry sectors including the manufacturing, knowledge, and services industries, while exerting weaker forces in pulling agglomeration in its immediate environs among other industries (including the retail trade sector). In practice, these results are useful for justifying evidence-based rail transit planning.
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Diabetic cardiomyopathy (DCM) is a prevalent myocardial microvascular complication of the myocardium with a complex pathogenesis. Investigating the pathogenesis of DCM can significantly contribute to enhancing its prevention and treatment strategies. Our study revealed an upregulation of lysine acetyltransferase 2 A (Kat2a) expression in DCM, accompanied by a decrease in N6-methyladenosine (m6A) modified Kat2a mRNA levels. Our study revealed an upregulation of lysine acetyltransferase 2 A (Kat2a) expression in DCM, accompanied by a decrease in N6-methyladenosine (m6A) modified Kat2a mRNA levels. Functionally, inhibition of Kat2a effectively ameliorated high glucose-induced cardiomyocyte injury both in vitro and in vivo by suppressing ferroptosis. Mechanistically, Demethylase alkB homolog 5 (Alkbh5) was found to reduce m6A methylation levels on Kat2a mRNA, leading to its upregulation. YTH domain family 2 (Ythdf2) played a crucial role as an m6A reader protein mediating the degradation of Kat2a mRNA. Furthermore, Kat2a promoted ferroptosis by increasing Tfrc and Hmox1 expression via enhancing the enrichment of H3K27ac and H3K9ac on their promoter regions. In conclusion, our findings unveil a novel role for the Kat2a-ferroptosis axis in DCM pathogenesis, providing valuable insights for potential clinical interventions.
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Cardiomiopatías Diabéticas , Ferroptosis , Hemo-Oxigenasa 1 , Histona Acetiltransferasas , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/patología , Cardiomiopatías Diabéticas/genética , Animales , Ferroptosis/genética , Humanos , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Ratones , Histona Acetiltransferasas/metabolismo , Histona Acetiltransferasas/genética , Masculino , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Adenosina/análogos & derivados , Adenosina/metabolismoRESUMEN
With the global population expected to reach 9.7 billion by 2050, there is an urgent need for advanced materials that can address existing and developing environmental issues. Many current synthesis processes are environmentally unfriendly and often lack control over size, shape, and phase of resulting materials. Based on knowledge from biological synthesis and assembly processes, as well as their resulting functions (e.g., photosynthesis, self-healing, anti-fouling, etc.), researchers are now beginning to leverage these biological blueprints to advance bio-inspired pathways for functional materials for water treatment, air purification and sensing. The result has been the development of novel materials that demonstrate enhanced performance and address sustainability. Here, an overview of the progress and potential of bio-inspired methods toward functional materials for environmental applications is provided. The challenges and opportunities for this rapidly expanding field and aim to provide a valuable resource for researchers and engineers interested in developing sustainable and efficient processes and technologies is discussed.
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Leveraging solar energy through photocatalytic hydrogen production from water stands out as one of the most promising approaches to address the energy and environmental challenges. The choice of catalyst profoundly influences the outcomes of photocatalytic reactions, and constructing heterojunctions has emerged as a widely applied strategy to overcome the limitations associated with single-phase photocatalysts. MoO3, renowned for its high chemical stability, encounters issues such as low photocatalytic efficiency and fast recombination of photogenerated electrons and holes. To tackle these challenges, the morphology of MoO3 has been controlled to form nanorods, simultaneously suppressing the aggregation of the catalyst and increasing the number of surface-active sites. Moreover, to facilitate the separation of photogenerated charge carriers, Cd0.9Zn0.1S nanoparticles with a twin crystal structure are deposited on the surface of MoO3, establishing an S-scheme heterojunction. Experimental findings demonstrate that the synergistic effects arising from the well-defined morphology and interface interactions extend the absorption range to visible light response, improve charge transfer activity, and prolong the lifetime of charge carriers. Consequently, Cd0.9Zn0.1S/MoO3 S-scheme heterojunctions exhibit outstanding photocatalytic hydrogen production performance (3909.79 µmol g-1 h-1) under visible light irradiation, surpassing that of MoO3 by nearly nine fold.
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BACKGROUND: The energy supply of certain cancer cells depends on aerobic glycolysis rather than oxidative phosphorylation. Our previous studies have shown that withaferin A (WA), a lactone compound derived from Withania somnifera, suppresses skin carcinogenesis at least partially by stabilizing IDH1 and promoting oxidative phosphorylation. Here, we have extended our studies to evaluate the anti-tumor effect of WA in liver cancer. METHODS: Differential expression of glycolysis-related genes between liver cancer tissues and normal tissues and prognosis were verified using an online database. Glycolysis-related protein expression was detected using western blot after overexpression and knockdown of IDH1 and mitochondrial membrane potential assay based on JC-1, and mitochondrial complex I activity was also detected. The inhibitory effect of WA on the biological functions of HepG2 cells was detected along with cell viability using MTT assay, scratch assay, clone formation assay, glucose consumption and lactate production assay. Western blot and qRT-PCR were used to detect the expression of proteins and genes related to IDH1, p53 and HIF1α signaling pathways. RESULTS: We first identified that IDH1 expression was downregulated in human liver cancer cells compared to normal liver cells. Next, we found that treatment of HepG2 cells with WA resulted in significantly increased protein levels of IDH1, accompanied by decreased levels of several glycolytic enzymes. Furthermore, we found that WA stabilized IDH1 proteins by inhibiting the degradation by the proteasome. The tumor suppressor p53 was also upregulated by WA treatment, which played a critical role in the upregulation of IDH1 and downregulation of the glycolysis-related genes. Under hypoxic conditions, glycolysis-related genes were induced, which was suppressed by WA treatment, and IDH1 expression was still maintained at higher levels under hypoxia. CONCLUSION: Taken together, our results indicated that WA suppresses liver cancer tumorigenesis by p53-mediated IDH1 upregulation, which promotes mitochondrial respiration, thereby inhibiting the HIF-1α pathway and blocking aerobic glycolysis.
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Glucólisis , Subunidad alfa del Factor 1 Inducible por Hipoxia , Isocitrato Deshidrogenasa , Neoplasias Hepáticas , Transducción de Señal , Proteína p53 Supresora de Tumor , Witanólidos , Humanos , Witanólidos/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Glucólisis/efectos de los fármacos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Transducción de Señal/efectos de los fármacos , Isocitrato Deshidrogenasa/genética , Isocitrato Deshidrogenasa/metabolismo , Proliferación Celular/efectos de los fármacos , Células Hep G2 , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Carcinogénesis/efectos de los fármacosRESUMEN
Electrocoagulation technology, due to its simplicity and ease of operation, is often considered for treating arsenic-contaminated groundwater. However, challenges such as anode wear have hindered its development and application. This study aims to develop a siderite-filled anode electrocoagulation system for efficient removal of As(iii) and investigate its effectiveness. The impact of operational parameters on the removal rate of As(iii) was analyzed through single-factor tests, and the stability and superiority of the device were evaluated. The response surface methodology was employed to analyze the interactions between various factors and determine the optimal operational parameters by integrating data from these tests. Under conditions where the removal rate of As reached 99.3 ± 0.37%, with an initial concentration of As(iii) at 400 µg L-1, current intensity at 30 mA, initial solution pH value at 7, and Na2SO4 concentration at 10 mM. The flocculant used was subjected to characterization analysis to examine its structure, morphology, and elemental composition under these optimal operational parameters. The oxidation pathway for As(iii) within this system relies on integrated results from direct electrolysis as well as ËO2 -, ËOH, and Fe(iv) mediated oxidation processes. The elimination of arsenic encompasses two fundamental mechanisms: firstly, the direct adsorption of As(iii) by highly adsorbent flocculants like γ-FeOOH and magnetite (Fe3O4); secondly, the oxidation of As(iii) into As(v), followed by its reaction with siderite or other compounds to generate a dual coordination complex or iron arsenate, thus expediting its eradication. The anodic electrocoagulation system employing siderite as a filler exhibits remarkable efficiency and cost-effectiveness, while ensuring exceptional stability, thereby providing robust theoretical underpinnings for the application of electrocoagulation technology in arsenic removal.
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Here, amphiphile GCH based on glutamide-cyanostilbene is designed and synthesized, it is found that it can assembly in acetonitrile, and shows circular dichroism signals. After Z-E isomerizaition by UV irradiation, the CD signal of the assembly can be inverted. Unexpectedly, after another heating and cooling process, the circular dichroism signals can be totally inverted even though the E-isomers are in minority. Finally, the molecular dynamics (MD) simulations deeply elucidate the supramolecuar chirality inversion mechanism. This work brings some new insights into the control of chirality inversion, which may provide a perspective for the smart chiroptical materials construction.
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Low discovery rates for new antibiotics, commercial disincentives to invest, and inappropriate use of existing drugs have created a perfect storm of antimicrobial resistance (AMR). This "silent pandemic" of AMR looms as an immense, global threat to human health. In tandem, many potential novel drug candidates are not progressed due to elevated hydrophobicity, which may result in poor intracellular internalization and undesirable serum protein binding. With a reducing arsenal of effective antibiotics, enabling technology platforms that improve the outcome of treatments, such as repurposing existing bioactive agents, is a prospective option. Nanocarrier (NC) mediated drug delivery is one avenue for amplifying the therapeutic outcome. Here, the performance of several antibiotic classes encapsulated within the lipid-based cubosomes is examined. The findings demonstrate that encapsulation affords significant improvements in drug concentration:inhibition outcomes and assists in other therapeutic challenges associated with internalization, enzyme degradation, and protein binding. We emphasize that a currently sidelined compound, novobiocin, became active and revealed a significant increase in inhibition against the pathogenic Gram-negative strain, Pseudomonas aeruginosa. Encapsulation affords co-delivery of multiple bioactives as a strategy for mitigating failure of monotherapies and tackling resistance. The rationale in optimized drug selection and nanocarrier choice is examined by transport modeling which agrees with experimental inhibition results. The results demonstrate that lipid nanocarrier encapsulation may alleviate a range of challenges faced by antibiotic therapies and increase the range of antibiotics available to treat bacterial infections.
Asunto(s)
Antibacterianos , Portadores de Fármacos , Lípidos , Pseudomonas aeruginosa , Antibacterianos/química , Antibacterianos/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Portadores de Fármacos/química , Lípidos/química , Nanopartículas/química , Pruebas de Sensibilidad Microbiana , Humanos , Sistemas de Liberación de MedicamentosRESUMEN
BACKGROUND: This study aimed to evaluate the effectiveness and safety of 2D laparoscopy vs 3D laparoscopy for the treatment of colorectal cancer. METHODS: A literature search was conducted through PubMed, Web of Science, and Embase from their inception to January 2024. Studies investigating different outcomes of colorectal surgery were included. Results are presented as odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs). The protocol for this review has been registered on PROSPERO (CRD42024504902). RESULTS: A total of 10 publications were retrieved in this article. The 3D group is associated with a significant improvement in intraoperative blood loss (MD = -8.04, 95% CI = -14.18 to -1.89, P = 0.01, I2 = 55%), operative time (MD = -17.33, 95% CI = -29.15 to -5.51, P = 0.004, I2 = 90%), and postoperative hospital stay (MD = -0.23, 95% CI = -0.43 to -0.04, P = 0.02, I2 = 48%) compared to that of patients treated in the 2D group, particularly for rectal cancer patients above three results (MD = -10.36, 95% CI = -15.00 to -5.73, P < 0.001, I2 = 0%), (MD = -18.85, 95% CI = -34.88 to -2.82, P = 0.02, I2 = 57%), and (MD = -0.93, 95% CI = -1.53 to -0.34, P = 0.002, I2 = 0%), respectively. There was no significant statistical difference in the time of pass flatus (MD = -0.14, 95% CI = -0.49 to 0.21, P = 0.44, I2 = 79%) and the number of dissected lymph nodes (MD = 0.36, 95% CI = -0.49 to 1.21, P = 0.41, I2 = 45%), but the 3D group had an earlier postoperative pass flatus for rectal cancer patients (MD = -0.46, 95% CI = -0.66 to -0.27, P<0.001, I2 = 0%) and the more number of dissected lymph nodes for colon cancer patients (MD = 1.54, 95% CI = 0.05 to 3.03, P = 0.04, I2 = 69%) than the 2D group. There was no significant difference in postoperative overall complication (OR = 0.94, 95% CI = 0.67 to 1.31, P = 0.71, I2 = 0%) and anastomotic leakage (OR = 0.93, 95% CI = 0.48 to 1.80, P = 0.83, I2 = 0%) in the two groups, regardless of rectal cancer and colon surgery patients. CONCLUSION: This meta-analysis demonstrates that 3D laparoscopy could reduce the amount of blood loss, accelerate postoperative pass flatus, and shorten the operation time and postoperative hospital stay over 2D for radical rectal cancer surgery, without obvious advantage for radical colon cancer surgery. Moreover, 3D laparoscopy increases the number of dissected lymph nodes for radical colon cancer surgery but may not be observed in rectal cancer surgery.