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Directly capturing atmospheric CO2 and converting it into valuable fuel through photothermal synergy is an effective way to mitigate the greenhouse effect. This study developed a gas-solid interface photothermal catalytic system for atmospheric CO2 reduction, utilizing the innovative photothermal catalyst (Cu porphyrin) CuTCPP/MXene/TiO2. The catalyst demonstrated a photothermal catalytic performance of 124 µmol·g-1·h-1 for CO and 106 µmol·g-1·h-1 for CH4, significantly outperforming individual components. Density functional theory (DFT) results indicate that the enhanced catalytic performance is attributed to the internal electric field between the components, which significantly enhances carrier utilization. The introduction of CuTCPP reduces free energy of the photothermal catalytic reaction. Additionally, the local surface plasmon resonance (LSPR) effect and high-speed electron transfer properties of MXene further boost the catalytic reaction rate. This well-designed catalyst and catalytic system offer a simple method for capturing atmospheric CO2 and converting it in-situ through photothermal catalysis.
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Bacteria-infected wounds pose challenges to healing due to persistent infection and associated damage to nerves and vessels. Although sonodynamic therapy can help kill bacteria, it is limited by the residual oxidative stress, resulting in prolonged inflammation. To tackle these barriers, novel 4 octyl itaconate-coated Li-doped ZnO/PLLA piezoelectric composite microfibers are developed, offering a whole-course "targeted" treatment under ultrasound therapy. The inclusion of Li atoms causes the ZnO lattice distortion and increases the band gap, enhancing the piezoelectric and sonocatalytic properties of the composite microfibers, collaborated by an aligned PLLA conformation design. During the infection and inflammation stages, the piezoelectric microfibers exhibit spatiotemporal-dependent therapeutic effects, swiftly eliminating over 94.2 % of S. aureus within 15 min under sonodynamic therapy. Following this phase, the microfibers capture reactive oxygen species and aid macrophage reprogramming, restoring mitochondrial function, achieving homeostasis, and shortening inflammation cycles. As the wound progresses through the healing stages, bioactive Zn2+ and Li + ions are continuously released, improving cell recruitment, and the piezoelectrical stimulation enhances wound recovery with neuro-vascularization. Compared to commercially available dressings, our microfibers accelerate the closure of rat wounds (Φ = 15 mm) without scarring in 12 days. Overall, this "one stone, four birds" wound management strategy presents a promising avenue for infected wound therapy.
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Terapia por Ultrassom , Cicatrização , Animais , Cicatrização/efeitos dos fármacos , Terapia por Ultrassom/métodos , Ratos Sprague-Dawley , Ratos , Staphylococcus aureus/efeitos dos fármacos , Óxido de Zinco/química , Camundongos , Estimulação Elétrica , Masculino , Infecções Estafilocócicas/terapia , Poliésteres/química , Espécies Reativas de Oxigênio/metabolismo , Terapia por Estimulação Elétrica/métodos , Neovascularização Fisiológica/efeitos dos fármacosRESUMO
To achieve highly efficient and environmentally degradable adsorbents for Congo red (CR) removal, we synthesized a dual-network nanocomposite cryogel composed of gelatin/carboxymethyl cellulose, loaded with Fe3O4 nanoparticles. Gelatin and sodium carboxymethylcellulose were cross-linked using transglutaminase and calcium chloride, respectively. The cross-linking process enhanced the thermal stability of the composite cryogels. The CR adsorption process exhibited a better fit to the pseudo-second-order model and Langmuir model, with maximum adsorption capacity of 698.19 mg/g at pH of 7, temperature of 318 K, and initial CR concentration of 500 mg/L. Thermodynamic results indicated that the CR adsorption process was both spontaneous and endothermic. The performance of machine learning model showed that the Extreme Gradient Boosting model had the highest test determination coefficient (R2 = 0.9862) and the lowest root mean square error (RMSE = 10.3901 mg/g) among the 6 models. Feature importance analysis using SHapley Additive exPlanations (SHAP) revealed that the initial concentration had the greatest influence on the model's prediction of adsorption capacity. Density functional theory calculations indicated that there were active sites on the CR molecule that can undergo electrostatic interactions with the adsorbent. Thus, the synthesized cryogels demonstrate promising potential as adsorbents for dye removal from wastewater.
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Cold maceration (CM) is widely applied in winemaking to improve wine aroma and overall quality. However, more efficient CM techniques for industrial-scale winemaking are still needed. This study examined the impact of CM with indigenous cryotolerant Metschnikowia pulcherrima Mp0520 (Mp-CM) on the Muscat wine aromatic characteristics. The results demonstrated a significant divergence in the types and concentrations of aroma compounds between Mp-CM wine and the control. The Mp-CM wine exhibited a significantly higher terpenes content, resulting in a Muscat wine characterized by terpenes, compared to the control predominated by esters. Additionally, the Mp-CM wine demonstrated elevated levels of α-terpineol and terpinolene, potentially enhancing the varietal aroma stability of Muscat wine. Furthermore, Mp-CM gave Muscat wine a heightened fruity aroma and a more complex aroma. These findings suggested that the Mp-CM utilized in this study offered promising avenues for enhancing the variety aroma characteristics of Muscat wine on large scale winemaking.
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Temperatura Baixa , Metschnikowia , Odorantes , Compostos Orgânicos Voláteis , Vinho , Vinho/análise , Odorantes/análise , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/análise , Metschnikowia/química , Humanos , Manipulação de Alimentos , Vitis/química , Terpenos/análise , Terpenos/químicaRESUMO
HF trimer, as the smallest and the lightest cyclic hydrogen-bonded (HB) cluster, has long been a favorite prototype system for spectroscopic and theoretical investigations of the structure, energetics, spectroscopy, and dynamics of hydrogen-bond networks. Recently, rigorous quantum 12D calculations of the coupled intra- and intermolecular vibrations of this fundamental HB trimer (J. Chem. Phys. 2023, 158, 234109) were performed, employing an older ab initio-based many-body potential energy surface (PES). While the theoretical results were found to be in reasonably good agreement with the available spectroscopic data, it was also evident that it is highly desirable to develop a more accurate 12D PES of HF trimer. Motivated by this, here we report a new, and the first fully ab initio 12D PES of this paradigmatic system. Approximately 42,540 geometries were sampled and calculated at the level of CCSD(T)-F12a/AVTZ. The permutationally invariant polynomial-neural network based Δ-machine learning approach (J. Phys. Chem. Lett. 2022, 13, 4729) was employed to perform cost-efficient calculations of the basis-set-superposition error (BSSE) correction. By strategically selecting data points, this approach facilitated the construction of a high-precision PES with BSSE correction, while requiring only a minimal number of BSSE value computations. The fitting error of the final PES is only 0.035 kcal/mol. To assess its performance, the 12D fully coupled quantum calculations of excited intra- and intermolecular vibrational states of HF trimer are carried out using the rigorous methodology developed by us earlier. The results are found to be in a significantly better agreement with the available spectroscopic data than those obtained with the previously existing semiempirical 12D PES.
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Infection is the most prevalent complication of fractures, particularly in open fractures, and often leads to severe consequences. The emergence of bacterial resistance has significantly exacerbated the burden of infection in clinical practice, making infection control a significant treatment challenge for infectious bone defects. The implantation of a structural stent is necessary to treat large bone defects despite the increased risk of infection. Therefore, there is a need for the development of novel antibacterial therapies. The advancement in antibacterial biomaterials and new antimicrobial drugs offers fresh perspectives on antibacterial treatment. Although antimicrobial 3D scaffolds are currently under intense research focus, relying solely on material properties or antibiotic action remains insufficient. Antimicrobial peptides (AMPs) are one of the most promising new antibacterial therapy approaches. This review discusses the underlying mechanisms behind infectious bone defects and presents research findings on antimicrobial peptides, specifically emphasizing their mechanisms and optimization strategies. We also explore the potential prospects of utilizing antimicrobial peptides in treating infectious bone defects. Furthermore, we propose that artificial intelligence (AI) algorithms can be utilized for predicting the pharmacokinetic properties of AMPs, including absorption, distribution, metabolism, and excretion, and by combining information from genomics, proteomics, metabolomics, and clinical studies with computational models driven by machine learning algorithms, scientists can gain a comprehensive understanding of AMPs' mechanisms of action, therapeutic potential, and optimizing treatment strategies tailored to individual patients, and through interdisciplinary collaborations between computer scientists, biologists, and clinicians, the full potential of AI in accelerating the discovery and development of novel AMPs will be realized. Besides, with the continuous advancements in 3D/4D/5D/6D technology and its integration into bone scaffold materials, we anticipate remarkable progress in the field of regenerative medicine. This review summarizes relevant research on the optimal future for the treatment of infectious bone defects, provides guidance for future novel treatment strategies combining multi-dimensional printing with new antimicrobial agents, and provides a novel and effective solution to the current challenges in the field of bone regeneration.
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BACKGROUND AND AIM: Gut microbiome-targeted therapies (MTTs), including prebiotics, probiotics, synbiotics, and fecal microbiota transplantation (FMT), have been widely used in inflammatory bowel diseases (IBD), but the best MTTs has not yet been confirmed. We performed a network meta-analysis (NMA) to examine this in ulcerative colitis (UC) and Crohn's disease (CD). METHODS: We searched for randomized controlled trials (RCTs) on the efficacy and safety of MTTs as adjuvant therapies for IBD until December 10, 2023. Data were pooled using a random effects model, with efficacy reported as pooled relative risks with 95% CIs, and interventions ranked according to means of surfaces under cumulative ranking values. RESULTS: Thirty-eight RCTs met the inclusion criteria. Firstly, we compared the efficacy of MTTs in IBD patients. Only FMT and probiotics were superior to placebo in all outcomes, but FMT ranked best in improving clinical response rate and clinical and endoscopic remission rate, and probiotics ranked second in reducing clinical relapse rate showed significant efficacy, while prebiotics ranked first showed nonsignificant efficacy. Subsequently, we conducted NMA for specific MTT formulations in UC and CD separately, which revealed that FMT, especially combined FMT via colonoscopy and enema, showed significant efficacy and was superior in improving clinical response and remission rate of active UC patients. As for endoscopic remission and clinical relapse, multistrain probiotics based on specific genera of Lactobacillus and Bifidobacterium showed significant efficacy and ranked best in UC. In CD, we found that no MTTs were significantly better than placebo, but synbiotics comprising Bifidobacterium and fructo-oligosaccharide/inulin mix and Saccharomyces ranked best in improving clinical remission and reducing clinical relapse, respectively. Moreover, FMT was safe in both UC and CD. CONCLUSIONS: FMT and multistrain probiotics showed superior efficacy in UC. However, the efficacy of MTTs varies among different IBD subtypes and disease stages; thus, the personalized treatment strategies of MTTs are necessary.
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Cardiac fibrosis is featured cardiac fibroblast activation and extracellular matrix accumulation. Ac4C acetylation is an important epigenetic regulation of RNAs that has been recently discovered, and it is solely carried out by NAT10, the exclusive enzyme used for the modification. However, the potential regulatory mechanisms of ac4C acetylation in myocardial fibrosis following myocardial infarction remain poorly understood. In our study, we activated fibroblasts in vitro using TGF-ß1 (20 ng/mL), followed by establishing a myocardial infarction mouse model to evaluate the impact of NAT10 on collagen synthesis and cardiac fibroblast proliferation. We utilized a NAT10 inhibitor, Remodelin, to attenuate the acetylation capacity of NAT10. In the cardiac fibrosis tissues of chronic myocardial infarction mice and cultured cardiac fibroblasts (CFs) in response to TGF-ß1 treatment, there was an elevation in the levels of NAT10 expression. This increase facilitated proliferation, the accumulation of collagens, as well as fibroblast-to-myofibroblast transition. Through the administration of Remodelin, we effectively reduced cardiac fibrosis in myocardial infarction mice by inhibiting NAT10's ability to acetylate mRNA. Inhibition of NAT10 resulted in changes in collagen-related gene expression and ac4C acetylation levels. Mechanistically, we found that NAT10 upregulates the acetylation modification of BCL-XL mRNA and enhances the stability of BCL-XL mRNA, thereby upregulating its protein expression, inhibiting the activation of Caspase3 and blocking the apoptosis of CFs. Therefore, the crucial involvement of NAT10-mediated ac4C acetylation is significant in the cardiac fibrosis progression, affording promising molecular targets for the treatment of fibrosis and relevant cardiac diseases.
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Fibroblastos , Fibrose , Infarto do Miocárdio , Animais , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Infarto do Miocárdio/genética , Acetilação , Camundongos , Fibroblastos/metabolismo , Fibroblastos/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Masculino , Proliferação de Células , Modelos Animais de Doenças , Fator de Crescimento Transformador beta1/metabolismo , Colágeno/metabolismo , Camundongos Endogâmicos C57BL , Apoptose , Acetiltransferase N-Terminal E/metabolismo , Acetiltransferase N-Terminal E/genética , Acetiltransferases N-Terminal/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patologiaRESUMO
Background: Psychiatric symptoms directly associated with SARS-CoV-2 virus infection have been reported sporadically in children. More cases of new-onset psychosis without severe cardinal symptoms, altered consciousness level, and psychogenic drug usage would offer compelling grounds for the association between the virus infection and psychosis. Methods: We collected the clinical data of pediatric patients with new onset psychiatric symptoms after the SARS-CoV-2 virus infection from December 2022 to Feb 2023 and followed up with them for 1 year. These children did not have severe respiratory, cardiovascular, or systemic symptoms. They were not given psychogenic drugs. We also searched Pubmed to identify previously reported acute onset psychiatric cases related to SARS-CoV-2 virus infection in children. We summarized these patients' clinical symptoms, laboratory examination, treatment, and prognosis. Results: We reported 11 new cases of psychiatric disease directly related to SARS-CoV-2 virus infection and reviewed 12 previously reported cases among children and adolescents. They had various psychiatric symptoms within 3 weeks after the virus infection. Brain MRI and EEG recording did not reveal remarkable abnormalities. The cerebrospinal fluid analysis (CSF) could find increased protein, immunoglobulin, and IL-8 levels, disrupted blood-brain barrier, and positive oligoclonal band in a minority of the patients. Most of the patients had good outcomes. Conclusion: New-onset psychiatric symptoms directly related to SARS-CoV-2 virus infection are not rare phenomena among pediatric patients. CSF tests support the presence of central immune responses in some patients. Although these patients received different treatments, most of them had good prognoses.
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Introduction: Studying the behavioral responses and movement trajectories of insects under different stimuli is crucial for developing more effective biological control measures. Therefore, accurately obtaining the movement trajectories and behavioral parameters of insects in three-dimensional space is essential. Methods: This study used the litchi pest Thalassodes immissaria as the research object. A special binocular vision observation system was designed for nighttime movement. A thermal infrared camera was used for video recording of T. immissaria in a lightless environment. Moreover, a multi-object tracking method based on the YOLOX-GMM and SORT-Pest algorithms was proposed for tracking T. immissaria in thermal infrared images. By obtaining the central coordinates of the two T. immissaria in the video, target matching and 3D trajectory reconstruction in the parallel binocular system were achieved. Results: Error analysis of the T. immissaria detection and tracking model, as well as the 3D reconstruction model, showed that the average accuracy of T. immissaria detection reached 89.6%, tracking accuracy was 96.9%, and the average error of the reconstructed 3D spatial coordinates was 15 mm. Discussion: These results indicate that the method can accurately obtain the 3D trajectory and motion parameters of T. immissaria. Such data can greatly contribute to researchers' comprehensive understanding of insect behavioral patterns and habits, providing important support for more targeted control strategies.
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Background: The long-term monitoring of biventricular function is essential to identify potential functional decline in patients following the arterial switch operation (ASO). The underlying pathophysiological mechanisms responsible for altered biventricular hemodynamics in ASO patients are not yet well understood. This study sought to: (I) compare the biventricular kinetic energy (KE) and vorticity of ASO patients and age- and sex-matched controls; (II) investigate the associations of four-dimensional (4D) flow biventricular hemodynamics parameters and neo-aortic root dilation, supravalvular pulmonary stenosis, and pulmonary artery transvalvular pressure difference. Methods: A total of 34 patients with dextro-transposition of the great arteries (D-TGA) who underwent ASO, and 17 age- and gender-matched healthy controls were prospectively recruited for this study. All the subjects underwent cine and 4D flow and late gadolinium enhancement scans, and all the patients underwent echocardiography within two weeks of cardiovascular magnetic resonance (CMR) imaging. The following four flow components were analyzed: direct flow, retained inflow, delayed ejection flow, and residual volume. In addition, the following six phasic blood flow KE parameters, normalized to the end-diastolic volume (EDV) and vorticity, were analyzed for both the left ventricle (LV) and right ventricle (RV): peak systolic phase, average systolic phase, peak diastolic phase, average diastolic phase, peak E-wave phase, and peak A-wave phase. The independent sample Student's t-test, Mann-Whitney U-test, univariable and multivariable stepwise regression analyses, intra and inter-observer variability analyses were used to compare patients and controls. Results: In relation to the LV, the D-TGA patients had significantly decreased average vorticity, peak systolic vorticity, systolic vorticity, diastolic vorticity, and peak A-wave vorticity compared to the controls (all P<0.01). In relation to the RV, the pulmonary stenosis group had significantly increased peak E- and A-wave kinetic energy normalized to the end-diastolic volume (KEiEDV), and peak and average vorticity compared to the non-pulmonary stenosis group (all P<0.05). in the multivariable logistic regression model analysis, diastolic KEiEDV, peak E-wave KEiEDV peak A-wave KEiEDV, and average vorticity were associated a with transvalvular pressure difference (ß=13.54, P<0.001 for diastolic KEiEDV; ß=105.26, P<0.001 for peak E-wave KEiEDV; ß=-49.36, P=0.027 for peak A-wave KEiEDV; and ß=-56.37, P<0.001 for average vorticity). Conclusions: We found that 4D flow biventricular hemodynamics were more sensitive markers than the ejection fraction in the postoperative D-TGA patients. The RV diastolic KEiEDV parameters and average vorticity were risk factors for pulmonary artery obstruction in the multivariable model.
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Background: Breast cancer is one of the most common malignancies in women worldwide, and early and accurate diagnosis is crucial for improving treatment outcomes. Conventional ultrasound (CUS) is a widely used screening method for breast cancer; however, the subjective nature of interpreting the results can lead to diagnostic errors. The current study sought to estimate the effectiveness of using a GoogLeNet deep-learning convolutional neural network (CNN) model to identify benign and malignant breast masses based on CUS. Methods: A literature search was conducted of the Embase, PubMed, Web of Science, Wanfang, China National Knowledge Infrastructure (CNKI), and other databases to retrieve studies related to GoogLeNet deep-learning CUS-based models published before July 15, 2023. The diagnostic performance of the GoogLeNet models was evaluated using several metrics, including pooled sensitivity (PSEN), pooled specificity (PSPE), the positive likelihood ratio (PLR), the negative likelihood ratio (NLR), the diagnostic odds ratio (DOR), and the area under the curve (AUC). The quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies Scale (QUADAS). The eligibility of the included literature were independently searched and assessed by two authors. Results: All of the 12 studies that used pathological findings as the gold standard were included in the meta-analysis. The overall average estimation of sensitivity and specificity was 0.85 [95% confidence interval (CI): 0.80-0.89] and 0.86 (95% CI: 0.78-0.92), respectively. The PLR and NLR were 6.2 (95% CI: 3.9-9.9) and 0.17 (95% CI: 0.12-0.23), respectively. The DOR was 37.06 (95% CI: 20.78-66.10). The AUC was 0.92 (95% CI: 0.89-0.94). No obvious publication bias was detected. Conclusions: The GoogLeNet deep-learning model, which uses a CNN, achieved good diagnostic results in distinguishing between benign and malignant breast masses in CUS-based images.
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Background: Stable angina pectoris (SAP), as a common type of coronary heart disease (CHD), is characterized by transient retrosternal squeezing pain or suffocation induced by exercise, mood swings, or other stress. Most patients with stable angina pectoris do not benefit from interventional therapy and medication, so optimizing treatment plans has important clinical significance. Jiuxin pill is a Chinese patent medicine developed by Huatuo Chinese Medicine Co. Ltd. (Bozhou, China) to relieve the symptoms of stable angina pectoris (SAP). However, there is a lack of evidence support from high-quality clinical studies. Methods: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, 170 patients with SAP were recruited from 11 centers in China. The patients were randomized to either the treatment group (Jiuxin pill, 2 pills, bid) or the control group (Jiuxin pill simulant, 2 pills, bid) without changing the original conventional western medicine. The trial was set up with a run-in period of 7 days, a treatment period of 28 ± 2 days, and a follow-up period of 28 ± 2 days. Total exercise time (TED) in the treadmill test and Seattle Angina Questionnaire (SAQ) scores were set as the main efficacy outcomes, and the 1-minute heart rate recovery (HRR1), metabolic equivalents (METs), maximum ST segment depression, Borg perceived exertion after exercise, the average number of angina attacks per week, usage of nitroglycerin, drug withdrawal and reduction rate, information scoring of four diagnostic methods in traditional Chinese medicine and incidence of major adverse cardiovascular events were set as the secondary efficacy outcomes. Adverse events were monitored throughout the trial. Discussion: In China, the use of Chinese patent medicine in the treatment of stable angina pectoris is more common. This trial evaluated the efficacy and safety of the Jiuxin pill in the treatment of patients with SAP, and the trial results provide high-quality research evidence for its clinical application. Trial Registration: This trial has been registered in the China Clinical Trial Registry on 11 June 2022 (Registration No.: ChiCTR2200060780, https://www.chictr.org.cn/showproj.html?proj=172352).
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Osteoporosis is a chronic metabolic disease that increases bone fragility and, leads to severe osteoporotic fractures. In recent years, the use of high-throughput omics to explore physiological and pathological biomarkers related to bone metabolism has gained popularity. In this review, we first briefly review the technical approaches of proteomics. Additionally, we summarize the relevant literature in the last decade to provide a comprehensive overview of advances in human proteomics related to osteoporosis. We describe the specific roles of various proteins related to human bone metabolism, highlighting their potential as biomarkers for risk assessment, early diagnosis and disease course monitoring in osteoporosis. Finally, we outline the main challenges currently faced by human proteomics in the field of osteoporosis and offer suggestions to address these challenges, to inspire the search for novel osteoporosis biomarkers and a foundation for their clinical translation. In conclusion, proteomics is a powerful tool for discovering osteoporosis-related biomarkers, which can not only provide risk assessment, early diagnosis and disease course monitoring, but also reveal the underlying mechanisms of disease and provide key information for personalized treatment. The translational potential of this article: This review provides an insightful summary of recent human-based studies on osteoporosis-associated proteomics, which can aid the search for novel osteoporosis biomarkers based on human proteomics and the clinical translation of research results.
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Aims: This study aimed to assess the effects of Low-to-Moderate Intensity Continuous Training (LMICT), Moderate-Intensity Interval Training (MIIT), and Reduced-Exertion High-Intensity Training (REHIT) on blood glucose regulation, functional recovery, and lipid levels in individuals who have experienced a stroke and are diagnosed with Type 2 Diabetes Mellitus (T2DM). Methods: Forty-two T2DM stroke patients were randomly allocated to four groups: LMICT, MIIT, REHIT, and a control group (CON). Participants continuously monitored their blood glucose levels throughout the intervention using continuous glucose monitoring (CGM) devices. The study comprised two exercise intervention cycles: the first lasting from Day 3 to Day 14 and the second from Day 15 to Day 28, with the initial two days serving as contrasting periods. Primary outcomes encompassed CGM-derived blood glucose measurements, the Barthel Index (BI), Fugl-Meyer Assessment lower-extremity subscale (FMA-LE), and alterations in triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c). Results: Compared with the CON, the MIIT group showed significant improvements in mean glucose (MG), glucose standard deviation (SD), time above range (TAR), and time in range (TIR). The REHIT group exhibited significantly reduced time below range (TBR), glucose SD, and coefficient of variation (CV). Regarding lipid levels, although the REHIT group achieved a significant reduction in TG levels compared with the CON, the overall effects of LMICT, MIIT, and REHIT on lipid profiles were relatively modest. Concerning functional recovery, the REHIT group significantly improved the BI and FMA-LE. Conclusion: Although the short-term quantitative impact of exercise on lipid levels may be limited, both REHIT and MIIT significantly improved glycemic management and reduced glucose variability in post-stroke patients with Type 2 Diabetes Mellitus. Additionally, REHIT notably enhanced functional recovery.
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Glicemia , Diabetes Mellitus Tipo 2 , Terapia por Exercício , Exercício Físico , Controle Glicêmico , Lipídeos , Acidente Vascular Cerebral , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Controle Glicêmico/métodos , Pessoa de Meia-Idade , Glicemia/metabolismo , Glicemia/análise , Idoso , Lipídeos/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/terapia , Exercício Físico/fisiologia , Terapia por Exercício/métodos , Reabilitação do Acidente Vascular Cerebral/métodosRESUMO
Acute myeloid leukemia (AML), which has distinct genetic abnormalities, has unique clinical and biological features. In this study, the incidence, clinical characteristics, induction treatment response, and outcomes of a large cohort of Chinese AML pediatric patients treated according to the BCH-AML 2005 protocol were analyzed. RUNX1-RUNX1T1 was the most common fusion transcript, followed by the CBFß-MHY11 and KMT2A rearrangements. FLT3-ITD and KIT mutations are associated with unfavorable clinical features and induction responses, along with KMT2A rearrangements, DEK-NUP214, and CBF-AML. The 5-year event-free survival (EFS) and overall survival (OS) rates of our cohort were 53.9 ± 3.7% and 58.5 ± 3.6%, with the best survival found among patients with CBFß-MYH11 and the worst survival among those with DEK-NUP214. In addition, we found that patients with FLT3-ITD mutation had adverse outcomes and that KIT mutation had a negative impact on OS in RUNX1-RUNX1T1+ patients. Furthermore, the risk classification and response to treatment after each induction block also influenced the prognosis, and HSCT after first remission could improve OS in high-risk patients. Not achieving complete remission after induction 2 was found to be an independent prognostic factor for OS and EFS. These findings indicate that genetic abnormalities could be considered stratification factors, predict patient outcomes, and imply the application of targeted therapy.
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Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Feminino , Criança , Pré-Escolar , China/epidemiologia , Adolescente , Lactente , Estudos de Coortes , Mutação , Proteínas de Fusão Oncogênica/genética , Resultado do Tratamento , PrognósticoRESUMO
Time reversal symmetry breaking in superconductors, resulting from external magnetic fields or spontaneous magnetization, often leads to unconventional superconducting properties. In this way, an intrinsic phenomenon called the Fulde-Ferrell-Larkin-Ovchinnikov (FFLO) state may be realized by the Zeeman effect. Here, we construct the FFLO state in an artificial CrOCl/NbSe2 van der Waals (vdW) heterostructure by utilizing the superconducting proximity effect of NbSe2 flakes. The proximity-induced superconductivity demonstrates a considerably weak gap of about 0.12 meV, and the in-plane upper critical field reveals the behavior of the FFLO state. First-principles calculations uncover the origin of the proximitized superconductivity, which indicates the importance of Cr vacancies or line defects in CrOCl. Moreover, the FFLO state could be induced by the inherent large spin splitting in CrOCl. Our findings not only provide a practical scheme for constructing the FFLO state but also inspire the discovery of an exotic FFLO state in other two-dimensional vdW heterostructures.
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Chlorantraniliprole (CHL), a favored agricultural insecticide, is renowned for its high efficiency and broad-spectrum effectiveness against lepidoptera insects. However, the urgency for new insecticide development is underscored by the intricate multistep preparation process and modest overall yields of CHL, along with the escalating challenge of insect resistance. In response, we have crafted CHL mimics from proline employing computer-aided drug design. Molecular docking analysis of CHL's interactions with the ryanodine receptor (RyR) revealed that the nitrogen atom within the pyrazole moiety does not engage in pivotal interactions. Its removal may not abolish bioactivity entirely but could substantially simplify the synthetic process, thereby enhancing atom economy. This revelation prompted the exclusion of nitrogen and the subsequent formation of a pyrrole ring, enabling the meticulous design of synthetic pathways characterized by cost-effective precursors, streamlined synthesis, the avoidance of toxic reagents, minimal instrumentation, and high yields in the pursuit of innovative RyR modulators. Among these modulators, A1 and B1, obtained with yields exceeding 60%, showcased exceptional insecticidal potency, with LC50 values spanning from 0.12 to 1.47 mg L-1 against P. xylostella and M. separate. The inhibitory effects of these two compounds on insect detoxification enzymes imply a reduced likelihood of eliciting resistance in comparison to CHL, a finding further corroborated by their insecticidal potency against resistant pests. Moreover, molecular docking, MD simulations, and DFT calculations provided valuable structural insights, potentially unraveling the superior insecticidal activity of these two molecules, and thus paving the way for developing more potent insecticides.
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Frostbite is the most common cold injury and is caused by both immediate cold-induced cell death and the gradual development of localized inflammation and tissue ischemia. Delayed healing of frostbite often leads to scar formation, which not only causes psychological distress but also tends to result in the development of secondary malignant tumors. Therefore, a rapid healing method for frostbite wounds is urgently needed. Herein, we used a mouse skin model of frostbite injury to evaluate the recovery process after frostbite. Moreover, single-cell transcriptomics was used to determine the patterns of changes in monocytes, macrophages, epidermal cells and fibroblasts during frostbite. Most importantly, human-induced pluripotent stem cell (hiPSC) -derived skin organoids combining with gelatin-hydrogel were constructed for the treatment of frostbite. The results showed that skin organoid treatment significantly accelerated wound healing by reducing early inflammation after frostbite and increasing the proportions of epidermal stem cells. Moreover, in the later stage of wound healing, skin organoids reduced the overall proportions of fibroblasts, significantly reduced fibroblast-to-myofibroblast transition by regulating the integrin α5ß1-FAK pathway, and remodeled the extracellular matrix (ECM) through degradation and reassembly mechanisms, facilitating the restoration of physiological ECM and reducing the abundance of ECM associated with abnormal scar formation. These results highlight the potential application of organoids for promoting the reversal of frostbite-related injury and the recovery of skin functions. This study provides a new therapeutic alternative for patients suffering from disfigurement and skin dysfunction caused by frostbite.
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Active immunization (vaccination) induces long-lasting immunity with memory, which takes weeks to months to develop. Passive immunization (transfer of neutralizing antibodies) provides immediate protection, yet with high cost and effects being comparatively short-lived. No currently approved adjuvants are compatible with formulations to combine active and passive immunizations, not to mention their huge disparities in administration routes and dosage. To solve this, we engineered the Fc fragment of human IgG1 into a hexamer nanoparticle and expressed its afucosylated form in Fut8-/- CHO cells, naming it "FcRider." FcRider is highly soluble with long-term stability, easily produced at high levels equivalent to those of therapeutic antibodies, and is amenable to conventional antibody purification schemes. Most importantly, FcRider possesses endogenous adjuvant activities. Using SWHEL B cell receptor (BCR) transgenic mice, we found that HEL-FcRider induced GL7+ germinal center B cells and HEL-specific IgG. Similarly, immunizing mice with UFO-BG-FcRider, a fusion containing the stabilized human immunodeficiency virus-1 (HIV-1) Env protein as immunogen, promoted somatic hypermutation and generation of long CDR3 of the IgG heavy chains. Intramuscular injection of (Fba + Met6)3-FcRider, a fusion with two peptide epitopes from Candida albicans cell surface, stimulated strong antigen-specific IgG titers. In three different models, we showed that afucosylated FcRider functions as a multivalent immunogen displayer and stimulates antigen-specific B cells without any exogenous adjuvant. As an antibody derivative, afucosylated FcRider could be a novel platform combining vaccines and therapeutic antibodies, integrating active and passive immunizations into single-modality "hybrid immunization" to provide complete and long-lasting protection against infections, and may open new avenues in cancer immunotherapy as well.