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BACKGROUND: Left ventricular hypertrophy (LVH) is highly prevalent in haemodialysis (HD) patients and is associated with an increased risk of death. Roxadustat and recombinant human erythropoietin (rHuEPO, abbreviated as EPO) are the main treatment strategies for renal anaemia in HD patients, but it has not been clear whether there is a difference in their effect on LVH. METHODS: In this multi-centre, prospective, randomized trial of 12-month duration, study participants were randomized in a 1:1 ratio to the roxadustat group or the EPO group. The doses of both treatment regimens were adjusted so that the patients had a haemoglobin level of 10.0-12.0 g per dL. The primary study endpoint was the change from baseline to 12 months in the left ventricular mass index (LVMI, g/m2) measured by echocardiography. RESULTS: In total, 114 patients were enrolled. The mean age was 50 years, and the median dialysis duration was 33 months. Sixty-one patients were men, and 24 were diabetic. LVMI decreased from 116.18 ± 27.84 to 110.70 ± 25.74 g/m2 in the roxadustat group. However, it increased from 109.35 ± 23.41 to 114.99 ± 28.46 g/m2 in the EPO group, with a significant difference in the change in LVMI between the two groups [-5.48 (-11.60 to 0.65) vs. 5.65 (0.74 to 10.55), p < 0.05]. Changes in left ventricular mass, end-diastolic volume and 6-min walk test seemed superior in the roxadustat group. There were no significant differences in other cardiac geometry, biochemical parameters and major adverse cardiovascular events between the two groups. CONCLUSIONS: Compared to EPO, roxadustat is more helpful in the regression of LVH in HD patients.
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Anemia , Eritropoyetina , Fallo Renal Crónico , Masculino , Humanos , Persona de Mediana Edad , Femenino , Estudios Prospectivos , Diálisis Renal/efectos adversos , Anemia/etiología , Anemia/complicaciones , Eritropoyetina/uso terapéutico , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/etiología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapiaRESUMEN
The atomic precision of the subnanometer nanoclusters has provided sound proof on the structural correlation of metal complexes and larger-sized metal nanoparticles. Herein, we report the synthesis, crystallography, structural characterization, electrochemistry, and optical properties of a 133-atom intermetallic nanocluster protected by 57 thiolates (3-methylbenzenethiol, abbreviated as m-MBTH) and 3 chlorides, with the formula of Ag125Cu8(m-MBT)57Cl3. This is the largest Ag-Cu bimetallic cluster ever reported. Crystallographic analysis revealed that the nanocluster has a three-layer concentric core-shell structure, Ag7@Ag47@Ag71Cu8S57Cl3, and the Ag54 metal kernel adopts a D5h symmetry. The nuclei number is between that of the previously reported large silver cluster [Ag136(SR)64Cl3Ag0.45]- and the large silver-rich cluster Au130-xAgx(SR)55 (x = 98). All these three clusters bear a similar metallic core structure, while the main structural difference lies in the shell motif structures. Electron counting revealed an open electron shell with 73 delocalized electrons, which was verified by the electron paramagnetic resonance analysis. The DPV electrochemical measurement indicates a multielectron state quantization double-layer charging shape and single-electron sequential charging and discharging characteristic of the AgCu alloy cluster. In addition, the open-hole Z-scan test reveals the nonlinear optical absorption (2-3 optical absorption in the NIR-II/III region) of Ag125Cu8 nanoclusters.
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Microvascular decompression (MVD) is the preferred treatment for hemifacial spasm (HFS) and trigeminal neuralgia (TN), and fully endoscopic microvascular decompression (E-MVD) has been widely discussed in recent years. Considering the endoscopic diving technique used in endoscopic transsphenoidal pituitary adenoma resection, we developed the endoscopic semidiving technique. This technique involves preserving some cerebrospinal fluid (CSF) and positioning the endoscope at an appropriate distance from it; the potential advantages include reducing cerebellar retraction, accurately identifying the responsible vessels and minimizing mechanical damage. This study aimed to preliminarily evaluate the safety and feasibility of the semidiving technique in E-MVD. A total of 359 patients with HFS and TN scheduled to undergo E-MVD were included in the study. Patients with each disease were divided into a nonsemidiving technique group and a semidiving technique group. Surgical data, postoperative outcomes, complications, and recurrence rates were compared between the groups. In patients with HFS, the effective rate was 95.6% (nonsemidiving)and 92.9% (semidiving) respectively, with no statistically significant difference. The semidiving technique group had a lower incidence of postoperative permanent hearing loss compared with the nonsemidiving technique group (0% vs. 5.9%). In TN patients, no significant differences in effectiveness or postoperative complications were observed. The application of the semidiving technique in E-MVD for HFS not only ensures surgical quality and postoperative efficacy but also reduces the incidence of postoperative hearing loss, shortens the surgical duration and reduces the number of postoperative hospitalization days, aligning with the concept of enhanced recovery after surgery (ERAS).
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Espasmo Hemifacial , Cirugía para Descompresión Microvascular , Neuralgia del Trigémino , Humanos , Cirugía para Descompresión Microvascular/métodos , Femenino , Masculino , Persona de Mediana Edad , Neuralgia del Trigémino/cirugía , Anciano , Adulto , Resultado del Tratamiento , Espasmo Hemifacial/cirugía , Complicaciones Posoperatorias/epidemiología , Neuroendoscopía/métodos , Endoscopía/métodos , Neoplasias Hipofisarias/cirugíaRESUMEN
Objective: The objective of this study was to assess the short-term clinical efficacy of the short-term clinical efficacy of bone cement intramedullary support combined with locked plate fixation in the treatment of such fractures. Methods: A retrospective study including 21 patients was reviewed at an urban level one trauma center. There were 17 males and 4 females, with a mean age of 33.9 years. Gustilo grade was II (12 cases), III-A (6 cases), III-B (2 cases), and III-C (1 case). Two fractures were AO-OTA type 33A3, 9 cases were type 33C2, and 10 cases were type 33C3. After the first stage debridement and temporary external fixation, all patients received bone cement intramedullary support combined with locked plate fixation through an anterolateral incision at the second stage.. The perioperative complications, need for bone graft, alignment, and radiographic union were recorded. At 1-year follow-up, the range of knee motion was recorded, and functional results were evaluated by the Hospital for Special Surgery (HSS) knee score. Results: All 21 patients were followed up for 12-36 months, with an average of 18.7 months. 1 case had superficial wound infection, and 2 cases had partial skin edge necrosis of the original open wound. After symptomatic dressing changes, they all healed well. 4 cases had autogenous bone grafting. 18 patients (85.7%) achieved radiographic union, with a mean union time of 6.2 months. Two patients underwent secondary operation 9 months after surgery due to nonunion and finally united after autologous bone grafting. One patient developed a deep infection 8 months after surgery and was successfully treated with Masquelet technique. Finally, bone union was achieved 7 months after surgery. The alignment was good in 17 patients (81.0%). No deep infection or hardware failure occurred during 1-year follow-up. The average range of knee extension and flexion was 5.2 ° and 106.8 °, respectively. The HSS score averaged 83.6. Conclusions: Bone cement intramedullary support combined with locked plate fixation was an effective treatment modality of open distal femur fractures with high union rate, low complication, adequate alignment and satisfactory functional outcomes.
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BACKGROUND: Locking plates are widely used in open reduction internal fixation (ORIF) for proximal humeral fracture (PHF). However, the optimal surgical treatment of unstable, displaced PHF in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes of surgical treatment of PHF in the elderly with locking plate (LP) alone and locking plate combined with 3D printed polymethylmethacrylate (PMMA) prosthesis augmentation (LP-PA). METHODS: From May 2015 to April 2021, a total of 97 patients aged ≥ 60 years with acute unstable PHF who underwent osteosynthesis with either LP (46 patients) or LP-PA (51 patients) were retrospectively analyzed. For the LP-PA group, a customized proximal humeral prosthesis made of PMMA cement was intra-operatively fabricated by a three-dimensional (3D) printed prototype mold for the humeral medial support. Radiological outcomes were analyzed by measuring the value of neck-shaft angle (NSA) and humeral head height (HHH). The clinical outcomes were evaluated using Constant-Murley Score (CMS), Disabilities of the Arm Shoulder and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) score, and the shoulder range of motion (ROM). Pain was measured using a visual analogue scale (VAS). RESULTS: At the one-year follow-up, all fractures healed radiologically and clinically. The mean changes of NSA and HHH over the follow-up period were markedly smaller in the LP-PA group (3.8 ± 0.9° and 1.7 ± 0.3 mm) than those in the LP group (9.7 ± 2.1° and 3.2 ± 0.6 mm, both P < 0.0001). The LP-PA group also presented lower DASH score (17.1 ± 3.6), higher ASES score (89.5 ± 11.2) and better ROM in forward elevation (142 ± 26°) and external rotation (59 ± 11°) compared to the LP group (28.9 ± 4.8 for DASH score, P < 0.0001; 82.3 ± 9.0 for ASES score, P < 0.001; 129 ± 21° for forward elevation, P = 0.008; and 52 ± 9° for external rotation, P = 0.001). There was no significant difference in overall complication rate between the two groups, although the complication rate of screw perforation was higher in the LP-PA group (P = 0.172). CONCLUSIONS: For PHF in elderly patients, the combination of LP fixation and PMMA prosthesis augmentation effectively improved humeral head support and reduction maintenance, providing satisfactory outcomes both radiologically and clinically. This technique also reduced the incidence of screw perforation associated with plate fixation alone, making it a reasonable option to ensure satisfactory clinical outcomes.
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1,2,4-butanetriol (BT) is a polyol with unique chemical properties, which has a stereocenter and can be divided into D-BT (the S-enantiomer) and L-BT (the R-enantiomer). BT can be used for the synthesis of 1,2,4-butanetriol trinitrate, 3-hydroxytetrahydrofuran, polyurethane, and other chemicals. It is widely used in the military industry, medicine, tobacco, polymer. At present, the BT is mainly synthesized by chemical methods, which are accompanied by harsh reaction conditions, poor selectivity, many by-products, and environmental pollution. Therefore, BT biosynthesis methods with the advantages of mild reaction conditions and green sustainability have become a current research hotspot. In this paper, the research status of microbial synthesis of BT was summarized from the following three aspects: (1) the biosynthetic pathway establishment for BT from xylose; (2) metabolic engineering strategies employed for improving BT production from xylose; (3) other substrates for BT production. Finally, the challenges and prospects of biosynthetic BT were discussed for future methods to improve competitiveness for industrial production.
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Butanoles , Xilosa , Contaminación AmbientalRESUMEN
The flame retardants and electromagnetic interference (EMI) shielding performance were enhanced by using imidazolium-functionalized polyurethane (IPU) modified multi-walled carbon nanotubes (CNTs) and ammonium polyphosphate (APP) for polylactic acid (PLA)/polycaprolactone (PCL) composites. The PLA/PCL/10APP/8CNT/1.6IPU composite containing 10 wt% APP and 8 wt% imidazolium modified CNTs reached the limiting oxygen index (LOI) value of 30.3 % and passed the V-0 rating in UL-94 tests. Moreover, the peak of the heat release rate (pHRR) and total heat release (THR) for this composite reached around 302 kW/m2 and 64 KJ/m2, which were decreased by 39.1 % and 15.8 % compared with that of PLA/PCL/10APP composite. The improved flame retardancy was attributed to the interplay of catalytic, barrier, and condensed char forming of imidazolium-modified CNTs and APP. IPU catalyzed the charring effect of the polymer matrix during combustion and regulated the migration of more CNTs to disperse at the two-phase interface. The dispersion of imidazolium-modified CNTs and co-continuous phase structure of the composites can establish continuous conductive pathways. The PLA/PCL/APP/CNT/IPU composite obtained a higher conductivity compared to the PLA/PCL/APP/CNT composite and whose EMI SE reached 33.9 dB, which is a promising candidate for next-generation sustainable and protective plastics.
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Caproatos , Retardadores de Llama , Lactonas , Nanotubos de Carbono , Poliésteres , Catálisis , Conductividad Eléctrica , PolifosfatosRESUMEN
NLRC5, the largest member of the nucleotide-binding and oligomerization domain (NOD)-like receptor (NLR) family, has been reported to participate in the regulation of immune function and is associated with chronic inflammatory diseases. However, the biological function of NLRC5 in hepatocellular carcinoma (HCC) has not been fully demonstrated. The aim of this study is to evaluate NLRC5 expression in the tumor tissues of HCC patients undergoing surgical treatment, assess its prognostic value, and explore its relationship with critical immune-related molecules within the tumor microenvironment. A total of 100 patients with hepatitis B virus-associated HCC receiving surgical treatment were enrolled in the study. Immunohistochemical results were obtained by scoring the intensity of cellular staining and the percentage of positive cells in the tissue sections. The association between NLRC5 expression levels and the main clinicopathological factors was analyzed by Chi-square test method. The prognostic values were analyzed by COX regression model and the Kaplan-Meier survival curve. Receiver operating characteristic (ROC) curve analysis was performed to assess the predictive performance of NLRC5 in postoperative patients with HCC. IHC showed that high expression of NLRC5 was observed in 67% of HCC tissue samples. Chi-square test showed that NLRC5 was a risk factor associated with tumor number, satellite nodule, and envelope invasion. Kaplan-Meier survival curves and COX survival analysis showed that high expression of NLRC5 was significantly associated with decreased overall survival (OS) in HCC patients (HR = 1.79, 95% CI 1.03-3.12, p = .041). However, univariate logistic regression analysis revealed that NLRC5 showed positive relationship with GZMB and CD8α suggesting its role in immune escape of HCC. ROC curve analysis showed that the combination of tumor number, envelope invasion, and NLRC5 expression (area under the curve = 0.824, sensitivity = 77.30%, specificity = 82.4%) can more accurately evaluate the prognosis of HCC patients compared to the combination of only tumor number and envelope invasion (area under the curve = 0.690, sensitivity = 43.9%, specificity = 94.1%).NLRC5 plays a crucial role in progression of HCC and can be considered as a potential prognostic and predictive biomarker. Targeting NLRC5 may provide an attractive therapeutic approach for HCC.
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Biomarcadores de Tumor , Carcinoma Hepatocelular , Péptidos y Proteínas de Señalización Intracelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Masculino , Femenino , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Persona de Mediana Edad , Pronóstico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Adulto , Anciano , Estimación de Kaplan-Meier , Curva ROC , Microambiente Tumoral , Inmunohistoquímica , Relevancia ClínicaRESUMEN
Introduction: Periodicity, self-excitation, and time ratio asymmetry are the fundamental characteristics of the human gait. In order to imitate these mentioned characteristics, a pattern generator with four degrees of freedom is proposed based on cardioid oscillators developed by the authors. Method: The proposed pattern generator is composed of four coupled cardioid oscillators, which are self-excited and have asymmetric time ratios. These oscillators are connected with other oscillators through coupled factors. The dynamic behaviors of the proposed oscillators, such as phase locking, time ratio, and self-excitation, are analyzed via simulations by employing the harmonic balance method. Moreover, for comparison, the simulated trajectories are compared with the natural joint trajectories measured in experiments. Results and discussion: Simulation and experimental results show that the behaviors of the proposed pattern generator are similar to those of the natural lower limb. It means the simulated trajectories from the generator are self-excited without any additional inputs and have asymmetric time ratios. Their phases are locked with others. Moreover, the proposed pattern generator can be applied as the reference model for the lower limb exoskeleton controlling algorithm to produce self-adjusted reference trajectories.
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Aflatoxin B1 (AFB1), a pernicious constituent of the aflatoxin family, predominantly contaminates cereals, oils, and their derivatives. Acknowledged as a Class I carcinogen by the World Health Organization (WHO), the expeditious and quantitative discernment of AFB1 remains imperative. This investigation delineates that aluminum ions can precipitate the coalescence of iodine-modified silver nanoparticles, thereby engendering hot spots conducive for label-free AFB1 identification via Surface-Enhanced Raman Spectroscopy (SERS). This methodology manifests a remarkable limit of detection (LOD) at 0.47 fg/mL, surpassing the sensitivity thresholds of conventional survey techniques. Moreover, this method has good anti-interference ability, with a relative error of less than 10% and a relative standard deviation of less than 6% in quantitative results. Collectively, these findings illuminate the substantial application potential and viability of this approach in the quantitative analysis of AFB1, underpinning a significant advancement in food safety diagnostics.
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Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical applied as a plasticizer. As an environmental toxicant, DEHP poses a serious health threat. Many studies have revealed that DEHP can cause lead to various degrees of damage to the kidney. However, the evidence of DEHP-induced renal ferroptosis has not been reported. The purpose of this work was to probe the specific role of lipophagy in DEHP-induced renal injury and to investigate the relationship between lipophagy and ferroptosis. Quail were treated with DEHP (250 mg/kg BW/day, 500 mg/kg BW/day and 750 mg/kg BW/day) for 45 days. Microstructural and ultrastructural observations showed that DEHP caused damage to glomerular and tubular cells, and autophagy with multilayer structures were observed, suggesting that DEHP can induce lipophagy. The results indicated that the iron homeostasis was abnormal and the lipid peroxidation was increased. SLC7A11 and SLC3A2 were down-regulated. PTGS2, ACSL4 and LPCAT3 were elevated. In conclusion, DEHP could induce lipid peroxidation, lead to ferroptosis, and damage renal cells. Therefore, the relationship between lipophagy and ferroptosis was elucidated, which provided a new basis for intervention and prevention of DEHP increased diseases.
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Dietilhexil Ftalato , Ferroptosis , Ácidos Ftálicos , Animales , Coturnix , Codorniz , Dietilhexil Ftalato/toxicidad , RiñónRESUMEN
The accumulation of senescent cells in kidneys is considered to contribute to age-related diseases and organismal aging. Mitochondria are considered a regulator of cell senescence process. Atrazine as a triazine herbicide poses a threat to renal health by disrupting mitochondrial homeostasis. Melatonin plays a critical role in maintaining mitochondrial homeostasis. The present study aims to explore the mechanism by which melatonin alleviates atrazine-induced renal injury and whether parkin-mediated mitophagy contributes to mitigating cell senescence. The study found that the level of parkin was decreased after atrazine exposure and negatively correlated with senescent markers. Melatonin treatment increased serum melatonin levels and mitigates atrazine-induced renal tubular epithelial cell senescence. Mechanistically, melatonin maintains the integrity of mitochondrial crista structure by increasing the levels of mitochondrial contact site and cristae organizing system, mitochondrial transcription factor A (TFAM), adenosine triphosphatase family AAA domain-containing protein 3A (ATAD3A), and sorting and assembly machinery 50 (Sam50) to prevent mitochondrial DNA release and subsequent activation of cyclic guanosine 5'-monophosphate-adenosine 5'-monophosphate synthase pathway. Furthermore, melatonin activates Sirtuin 3-superoxide dismutase 2 axis to eliminate the accumulation of reactive oxygen species in the kidney. More importantly, the antisenescence role of melatonin is largely determined by the activation of parkin-dependent mitophagy. These results offer novel insights into measures against cell senescence. Parkin-mediated mitophagy is a promising drug target for alleviating renal tubular epithelial cell senescence.
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Background: Targeted agents are widely utilized in the treatment of ulcerative colitis (UC). Hence, a comprehensive understanding of comparative drug efficacy in UC is of great importance for drug development and clinical practice. Our objective was the quantitative evaluation of the comparative efficacy of targeted agents for UC. Methods: Three mathematical models were developed based on data from randomized controlled trials in patients with moderate-to-severe UC to describe the time-course and dose-response of efficacy defined as clinical remission, clinical response, and endoscopic improvement, as well as the placebo effect. The covariate effects were further evaluated. Model simulation was performed in a hypothetical population to compare the efficacies across different drugs. Results: The analysis dataset was composed of data from 35 trials of 12 drugs in UC. Time-response relationships were evaluated that indicated a gradual onset of drug efficacy in adalimumab, ozanimod, and Janus kinase (JAK) inhibitors. The dose-response relationships were estimated for each drug respectively. Patient age, disease duration, baseline weight, prior tumor necrosis factor (TNF) inhibitor exposure, and current treatment with corticosteroid showed an impact on efficacy, suggesting that younger patients with shorter UC duration without prior anti-TNF treatment and current corticosteroids therapy tend to display greater treatment effects. Conclusion: This study developed three longitudinal models for UC to quantitatively describe the efficacy of targeted agents, as well as the influencing factors of efficacy. Infliximab and upadacitinib were determined to be the most effective biological and small targeted molecules, respectively. These findings may provide valuable implications for guiding future decision-making in clinical practice and drug development for UC.
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The conditioning regimen is an important part of autologous hematopoietic stem cell transplantation (ASCT). We explored the efficacy and safety of an optimized BEAC (adjusted-dose, intermediate-dose cytarabine and reduced-dose cyclophosphamide, AD-BEAC) conditioning regimen for non-Hodgkin lymphoma (NHL). A total of 141 NHL patients received AD-BEAC or a standard-dose BEAC (SD-BEAC) conditioning regimen from January 2007 to December 2017, and 104 patients were included in the study after 1:1 propensity matching. The 5-year overall survival (OS) and progression free survival (PFS) rates were significantly higher with AD-BEAC than with SD-BEAC (82.7% vs. 67.3%, P = 0.039; 76.9% vs. 57.7%, P = 0.039). Transplant-related mortality (TRM) was 3.8% in both the AD-BEAC and SD-BEAC groups. The AD-BEAC group had lower incidence of oral ulcers and cardiotoxicity than the SD-BEAC group. An optimized BEAC conditioning regimen is an effective conditioning regimen for ASCT in NHL with acceptable toxicity, that is more effective and safer than a standard BEAC conditioning regimen.
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Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Citarabina , Trasplante de Células Madre Hematopoyéticas , Linfoma no Hodgkin , Acondicionamiento Pretrasplante , Trasplante Autólogo , Humanos , Acondicionamiento Pretrasplante/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma no Hodgkin/terapia , Linfoma no Hodgkin/mortalidad , Ciclofosfamida/administración & dosificación , Ciclofosfamida/uso terapéutico , Persona de Mediana Edad , Masculino , Femenino , Citarabina/administración & dosificación , Citarabina/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Resultado del Tratamiento , Anciano , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The interaction between the gut microbiota and mercaptopurine (6-MP), a crucial drug used in pediatric acute lymphoblastic leukemia (ALL) treatment, has not been extensively studied. Here we reveal the significant perturbation of gut microbiota after 2-week 6-MP treatment in beagles and mice followed by the functional prediction that showed impairment of SCFAs production and altered amino acid synthesis. And the targeted metabolomics in plasma also showed changes in amino acids. Additionally, targeted metabolomics analysis of feces showed changes in amino acids and SCFAs. Furthermore, ablating the intestinal microbiota by broad-spectrum antibiotics exacerbated the imbalance of amino acids, particularly leading to a significant decrease in the concentration of S-adenosylmethionine (SAM). Importantly, the depletion of gut microbiota worsened the damage of small intestine caused by 6-MP, resulting in increased intestinal permeability. Considering the relationship between toxicity and 6-MP metabolites, we conducted a pharmacokinetic study in pseudo germ-free rats to confirm that gut microbiota depletion altered the methylation metabolites of 6-MP. Specifically, the concentration of MeTINs, a secondary methylation metabolite, showed a negative correlation with SAM, the pivotal methyl donor. Additionally, we observed a strong correlation between Alistipes and SAM levels in both feces and plasma. In conclusion, our study demonstrates that 6-MP disrupts the gut microbiota, and depleting the gut microbiota exacerbates 6-MP-induced intestinal toxicity. Moreover, SAM derived from microbiota plays a crucial role in influencing plasma SAM and the methylation of 6-MP. These findings underscore the importance of comprehending the role of the gut microbiota in 6-MP metabolism and toxicity.
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Microbioma Gastrointestinal , Mercaptopurina , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Mercaptopurina/farmacocinética , Mercaptopurina/metabolismo , Perros , Ratones , Masculino , S-Adenosilmetionina/metabolismo , Heces/microbiología , Heces/química , Ratas , Metabolómica , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Aminoácidos/metabolismo , Antimetabolitos Antineoplásicos/farmacocinética , Antimetabolitos Antineoplásicos/efectos adversos , Antimetabolitos Antineoplásicos/toxicidad , Antibacterianos/farmacocinética , Antibacterianos/farmacología , Antibacterianos/efectos adversos , Ratones Endogámicos C57BLRESUMEN
Atrazine (ATZ) is a widely used herbicide that has toxic effects on animals. Melatonin (MLT) is a natural hormone with strong antioxidant properties. However, the effect of MLT on the glucose metabolism disorder caused by ATZ is still unclear. Mice were divided into four groups randomly and given 21 days of gavage: blank control group (Con), 5 mg/kg MLT group (MLT), 170 mg/kg ATZ group (ATZ), and 170 mg/kg ATZ and 5 mg/kg MLT group (ATZ + MLT). The results show that ATZ alters mRNA levels of metabolic enzymes related to glycogen synthesis and glycolysis and increased metabolites (glycogen, lactate, and pyruvate). ATZ causes abnormalities in glucose metabolism in mouse liver, interfering with glycemia regulation ability. MLT can regulate the endoplasmic reticulum to respond to disordered glucose metabolism in mice liver. This study suggested that MLT has the power to alleviate the ATZ-induced glycogen overdeposition and glycolytic deficit.
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Atrazina , Herbicidas , Melatonina , Ratones , Animales , Atrazina/farmacología , Melatonina/farmacología , Herbicidas/farmacología , Hígado/metabolismo , Estrés del Retículo Endoplásmico , Glucógeno/metabolismo , Glucosa/metabolismoRESUMEN
The atomic precision of sub-nanometer-sized metal nanoclusters makes it possible to elucidate the kinetics of metal nanomaterials from the molecular level. Herein, the size reduction of an atomically precise [Au23(CHT)16]- (HCHT = cyclohexanethiol) cluster upon ligand exchange with HSAdm (1-adamantanethiol) has been reported. During the 16 h conversion of [Au23(CHT)16]- to Au16(SR)12, the neutral 6e Au21(SR)15, and its 1e-reduction state, i.e. the 5e, cationic radical, [Au21(SR)15]+, are active intermediates to account for the formation of thermodynamically stable Au16 products. The combination of spectroscopic monitoring (with UV-vis and ESI-MS) and DFT calculations indicates the preferential size-reduction on the corner Au atoms on the core surface and the terminal Au atoms on longer AunSn+1 staples. This study provides a reassessment on the electronic state of the Au21 structure and highlights the single electron transfer processes in cluster systems and thus the importance of the EPR analysis on the mechanistic issues.
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BACKGROUND: Nanozymes, a new class of nanomaterials, have emerged as promising substitutes for enzymes in biosensor design due to their exceptional stability, affordability, and ready availability. While nanozymes address many limitations of natural enzymes, they still face challenges, particularly in achieving the catalytic activity levels of their natural counterparts. This indicates the need for enhancing the sensitivity of biosensors based on nanozymes. The catalytic activity of nanozyme can be significantly improved by regulating its size, morphology, and surface composition of nanomaterial. RESULTS: In this work, a kind of hollow core-shell structure was designed to enhance the catalytic activity of nanozymes. The hollow core-shell structure material consists of a nanozymes core layer, a hollow layer, and a MOF shell layer. Taking the classic peroxidase like Fe3O4 as an example, the development of a novel nanozyme@MOF, specifically p-Fe3O4@PDA@ZIF-67, is detailed, showcasing its application in enhancing the sensitivity of sensors based on Fe3O4 nanozymes. This innovative nanocomposite, featuring that MOF layer was designed to adsorb the signal molecules of the sensor to improve the utilization rate of reactive oxygen species generated by the nanozymes catalyzed reactions and the hollow layer was designed to prevent the active sites of nanozymes from being cover by the MOF layer. The manuscript emphasizes the nanocomposite's remarkable sensitivity in detecting hydrogen peroxide (H2O2), coupled with high specificity and reproducibility, even in complex environments like milk samples. SIGNIFICANCE AND NOVELTY: This work firstly proposed and proved that Fe3O4 nanozyme@MOF with hollow layer structure was designed to improve the catalytic activity of the Fe3O4 nanozyme and the sensitivity of the sensors based on Fe3O4 nanozyme. This research marks a significant advancement in nanozyme technology, demonstrating the potential of structural innovation in creating high-performance, sensitive, and stable biosensors for various applications.
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Técnicas Biosensibles , Estructuras Metalorgánicas , Técnicas Biosensibles/métodos , Estructuras Metalorgánicas/química , Óxido Ferrosoférrico/química , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/análisis , Indoles/química , Catálisis , Límite de Detección , Nanoestructuras/química , Nanocompuestos/química , Imidazoles , Polímeros , ZeolitasRESUMEN
Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by Fusarium strains that is harmful to the intestinal health of animals and is widely present in contaminated crops. The objective of this study was to investigate the potential therapeutic target of ZEN-induced jejunal damage in weaned gilts. Sixteen weaned gilts either received a basal diet or a basal diet supplemented with 3.0 mg/kg ZEN in a 32-day experiment. The results showed that ZEN at the concentration of 3.0 mg/kg diet activated the inflammatory response and caused oxidative stress of gilts (P < 0.05). ZEN exposure resulted in the up-regulation (P < 0.05) of the Exchange protein directly activated by the cAMP 1/Ras-related protein1/c-Jun N-terminal kinase (Epac1/Rap1/JNK signaling pathway in the jejunum of gilts in vivo and in the intestinal porcine epithelial cells in vitro. The cell viability, EdU-positive cells, and the mRNA expression of B-cell lymphoma-2 (Bcl-2) were decreased, whereas the reactive oxygen species production and the mRNA expressions of Bcl-2-associated X (Bax) and Cysteine-aspartic acid protease 3 (Caspase3) were increased (P < 0.05) by ZEN. However, ZEN increased the mRNA expression of Bcl-2 and decreased the mRNA expressions of Bax and caspase3 (P < 0.05) after the Epac1 was blocked. These results collectively indicated that 3.0 mg ZEN /kg diet induced jejunal damage via the Epac1/Rap1/JNK signaling pathway.
RESUMEN
Atrazine (ATR) is a widely used herbicide worldwide that can cause kidney damage in humans and animals by accumulation in water and soil. Lycopene (LYC), a carotenoid with numerous biological activities, plays an important role in kidney protection due to its potent antioxidant and anti-inflammatory effects. The current study sought to investigate the role of interactions between mtDNA and the cGAS-STING signaling pathway in LYC mitigating PANoptosis and inflammation in kidneys induced by ATR exposure. In our research, 350 mice were orally administered LYC (5 mg/kg BW/day) and ATR (50 or 200 mg/kg BW/day) for 21 days. Our results reveal that ATR exposure induces a decrease in mtDNA stability, resulting in the release of mtDNA into the cytoplasm through the mPTP pore and the BAX pore and the mobilization of the cGAS-STING pathway, thereby inducing renal PANoptosis and inflammation. LYC can inhibit the above changes caused by ATR. In conclusion, LYC inhibited ATR exposure-induced histopathological changes, renal PANoptosis, and inflammation by inhibiting the cGAS-STING pathway. Our results demonstrate the positive role of LYC in ATR-induced renal injury and provide a new therapeutic target for treating renal diseases in the clinic.