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BACKGROUND: An issue of pressing concern is the manganese contamination in farmland soils adjacent to industrial areas. To address this, intercropping hyperaccumulator plants with crops emerges as a sustainable approach to ensuring food security. This study aims to investigate the influence of intercropping Sedum alfredii with maize or soybean on their growth and the dynamics of manganese accumulation through field experiments. RESULTS: The results showed that compared with monoculture, the Sedum alfredii-maize intercropping system exhibited a land equivalent ratio (LER) of 1.89, signifying a 71.13% augmentation in bioaccumulation amount (BCA). Additionally, it led to a significant reduction in manganese content in various organs, ranging from 17.05% to 25.50%. However, the Sedum alfredii-soybean intercropping system demonstrated a LER of 1.94, accompanied by a 66.11% increase in BCA, but did not significantly reduce the manganese content in the roots, stems, and pods of soybeans. Furthermore, manganese accumulation in maize and soybean grains was primarily attributed to the aboveground translocation of manganese. The intercropping effect on blocking manganese absorption of maize during growth and maturity is primarily attributed to the earlier manganese accumulation in intercropped maize by 2.63 to 4.35 days, and a reduction of 21.95% in the maximum manganese accumulation rate. CONCLUSIONS: The study found that manganese accumulation dynamics vary significantly depending on the crop family. Intercropping Sedum alfredii with maize enhances land-use efficiency and reduces manganese uptake by crops, making it a promising strategy for remediating manganese-contaminated farmland near industrial areas. © 2024 Society of Chemical Industry.
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Perivascular adipose tissue (PVAT) is a unique fat depot surrounding blood vessels and plays a vital role in the progression of vascular remodeling and dysfunction. PVAT exhibits remarkable differences in structure, phenotype, origin, and secretome across anatomical locations. The proximity of PVAT to neighboring vascular beds favors a niche for bidirectional communication between adipocytes and vascular smooth muscle cells, endothelial cells, and immune cells. In this review, we update our understanding of PVAT's regional differences and provide a comprehensive exploration of how these differences impact cross-talks between PVAT and the vascular wall. Different PVAT depots show different degrees of vasoprotective function and resilience to pathological changes such as obesity and vasculopathies, shaping multifaceted interactions between PVAT depots and adjacent vasculatures. The depot-specific resilience may lead to innovative strategies to manage cardiometabolic disorders.
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OBJECTIVE: The objective of this work is to develop a novel myoelectric pattern recognition (MPR) method to mitigate the concurrent interference of electrode shift and loosening, thereby improving the practicality of MPR-based gestural interfaces towards intelligent control. METHODS: A Siamese auto-encoder network (SAEN) was established to learn robust feature representations against random occurrences of both electrode shift and loosening. The SAEN model was trained with a variety of shifted-view and masked-view feature maps, which were simulated through feature transformation operated on the original feature maps. Specifically, three mean square error (MSE) losses were devised to warrant the trained model's capability in adaptive recovery of any given interfered data. The SAEN was deployed as an independent feature extractor followed by a common support vector machine acting as the classifier. To evaluate the effectiveness of the proposed method, an eight-channel armband was adopted to collect surface electromyography (EMG) signals from nine subjects performing six gestures. RESULTS: Under the condition of concurrent interference, the proposed method achieved the highest classification accuracy in both offline and online testing compared to five common methods, with statistical significance (p < 0.05). CONCLUSION: The proposed method was demonstrated to be effective in mitigating the electrode shift and loosening interferences. SIGNIFICANCE: Our work offers a valuable solution for enhancing the robustness of myoelectric control systems.
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Background: The liver's regenerative capacity allows it to repair itself after injury. Extracellular vesicles and particles (EVPs) in the liver's interstitial space are crucial for signal transduction, metabolism, and immune regulation. Understanding the role and mechanism of liver-derived EVPs in regeneration is significant, particularly after partial hepatectomy, where the mechanisms remain unclear. Methods: A 70% hepatectomy model was established in mice, and EVPs were isolated and characterized using electron microscopy, nanocharacterization, and Western blot analysis. Combined metabolomic and transcriptomic analyses revealed ß-sitosterol enrichment in EVPs and activation of the Hedgehog signaling pathway during regeneration. The role of ß-sitosterol in EVPs on the Hedgehog pathway and its targets were identified using qRT-PCR, Western blot analysis. The regulation of carnitine synthesis by this pathway was determined using a dual luciferase assay. The effect of a ß-sitosterol diet on liver regeneration was verified in mice. Results: After 70% hepatectomy, the liver successfully regenerated without liver failure or death. At 24 hours post-surgery, tissue staining showed transient regeneration-associated steatosis (TRAS), with increased Ki67 positivity at 48 hours. EVPs displayed a spherical lipid bilayer structure with particle sizes of 70-130 nm. CD9, CD63, and CD81 in liver-derived EVPs were confirmed. Transcriptomic and metabolomic analyses showed EVPs supplementation significantly promoted carnitine synthesis and fatty acid oxidation. Tissue staining confirmed accelerated TRAS resolution and enhanced liver regeneration with EVP supplementation. Mass spectrometry identified ß-sitosterol in EVPs, which binds to Smo protein, activating the Hedgehog pathway. This led to the nuclear transport of Gli3, stimulating Setd5 transcription and inducing carnitine synthesis, thereby accelerating fatty acid oxidation. Mice with increased ß-sitosterol intake showed faster TRAS resolution and liver regeneration compared to controls. Conclusion: Liver-derived EVPs promote regeneration after partial hepatectomy. ß-sitosterol from EVPs accelerates fatty acid oxidation and promotes liver regeneration by activating Hedgehog signaling pathway.
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Vesículas Extracelulares , Proteínas Hedgehog , Hepatectomia , Regeneração Hepática , Fígado , Sitosteroides , Animais , Sitosteroides/farmacologia , Sitosteroides/química , Regeneração Hepática/efeitos dos fármacos , Regeneração Hepática/fisiologia , Vesículas Extracelulares/efeitos dos fármacos , Vesículas Extracelulares/química , Camundongos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Proteínas Hedgehog/metabolismo , Masculino , Transdução de Sinais/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Carnitina/farmacologia , Tamanho da PartículaRESUMO
Atmospheric rivers (ARs) reaching high-latitudes in summer contribute to the majority of climatological poleward water vapor transport into the Arctic. This transport has exhibited long term changes over the past decades, which cannot be entirely explained by anthropogenic forcing according to ensemble model responses. Here, through observational analyses and model experiments in which winds are adjusted to match observations, we demonstrate that low-frequency, large-scale circulation changes in the Arctic play a decisive role in regulating AR activity and thus inducing the recent upsurge of this activity in the region. It is estimated that the trend in summertime AR activity may contribute to 36% of the increasing trend of atmospheric summer moisture over the entire Arctic since 1979 and account for over half of the humidity trends in certain areas experiencing significant recent warming, such as western Greenland, northern Europe, and eastern Siberia. This indicates that AR activity, mostly driven by strong synoptic weather systems often regarded as stochastic, may serve as a vital mechanism in regulating long term moisture variability in the Arctic.
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The textile industry's high-salinity wastewater presents a significant difficulty for fractioning salts and dyes. To fractionate the dyes and salts, a high-performance CPVC composite loose nanofiltration membrane (LNM) was fabricated by interfacial polymerization. The organic phase was obtained by crosslinking polyethylenimine (PEI) with tannic acid (TA) and gallic acid (GA) using TMC. The resultant composite LNM performance was enhanced by adjusting the coating parameters, which included TA and GA concentrations as well as coating time. The study examined the effects of the total content of TA/PEI and GA/PEI concentrations on the chemical structure, surface roughness, and microstructure of the selective layer of LNM using SEM, AFM, FTIR, and water contact angle measurements. It also investigated the filtration performance of the membrane's selective layer, including pure water flux, PEG800 rejection rate, and membrane fouling analysis. However, the resultant membrane treated simulated reactive black 5 (RB5) dye wastewater. When the total content of TA/PEI is 4 kg L-1, the permeability of pure water flux is high at 7.5 L per m2 per h per bar when the total content of GA/PEI is 14 kg L-1 and the pure water flux is high at 8.8 L per m2 per h per bar. The overall PEG800 rejection rates were 97-98.98%. The optimal TA : PEI ratios reached a good pure water permeability up to 6.4 L per (m2 per h per bar) with a high rejection rate of 99.69% for a ratio 1/3 to dye, and GA : PEI ratios reached a good water permeability at 5.5 and 6.5 L per (m2 per h per bar) with rejection rates of 99.21% and 98.88% for ratio 1/3 and 3.5/10.5 for simulated RB5 dye, and the NaCl retention rate gradually decreased from 4% to 3%. The resultant LNM demonstrated promising applications in dye and salt fractionation.
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The adult mammalian cardiomyocyte has a limited capacity for self-renewal, which leads to the irreversible heart dysfunction and poses a significant threat to myocardial infarction patients. In the past decades, research efforts have been predominantly concentrated on the cardiomyocyte proliferation and heart regeneration. However, the heart is a complex organ that comprises not only cardiomyocytes but also numerous noncardiomyocyte cells, all playing integral roles in maintaining cardiac function. In addition, cardiomyocytes are exposed to a dynamically changing physical environment that includes oxygen saturation and mechanical forces. Recently, a growing number of studies on myocardial microenvironment in cardiomyocyte proliferation and heart regeneration is ongoing. In this review, we provide an overview of recent advances in myocardial microenvironment, which plays an important role in cardiomyocyte proliferation and heart regeneration.
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Executing go/no-go or approach/avoidance responses toward a stimulus can change its evaluation. To explain these effects, some theoretical accounts propose that executing these responses inherently triggers affective reactions (i.e., action execution), while others posit that the evaluative influences originate from interpreting these responses as valenced actions (i.e., action interpretation). To test the role of action execution and action interpretation in these evaluative effects, we developed a novel training task that combined both go/no-go and approach/avoidance actions orthogonally. Participants either responded or did not respond (i.e., go/no-go) to control a shopping cart on screen, and as a result, either collected or did not collect (i.e., approach/avoidance) certain food items. When the task instructions referred to the go/no-go actions (Experiment 1, N = 148), we observed an effect of these actions. Participants evaluated no-go items less positively than both go and untrained items. No effect of approach/avoidance actions was observed. Contrarily, when the task instructions referred to the approach/avoidance actions (Experiment 2, N = 158), we observed an approach/avoidance effect. Participants evaluated approached items more positively and avoided items less positively than untrained items. No effect of go/no-go actions was observed. This suggests that action interpretation determined whether go/no-go or approach/avoidance actions influenced stimulus evaluation, when the same motor responses were made. Further examination of the role of action interpretation can inform theories of how actions influence stimulus evaluation, and facilitate the use of these interventions in applied settings.
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Background: A subset of patients undergoing thyroid surgery for presumed benign thyroid disease presented with papillary thyroid microcarcinoma (PTMC). A non-invasive and precise method for early recognition of PTMC are urgently needed. The aim of this study was to construct and validate a nomogram that combines intratumoral and peritumoral radiomics features as well as clinical features for predicting PTMC in the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) 3 nodules using ultrasonography. Methods: A retrospective review was conducted on a cohort of 221 patients who presented with ACR TI-RADS 3 nodules. These patients were subsequently pathologically diagnosed with either PTMC or benign thyroid nodules. These patients were randomly divided into a training and test cohort with an 8:2 ratio for developing the clinical model, intratumor-region model, peritumor-region model and the combined-region model respectively. The radiomics features were extracted from ultrasound (US) images of each patient. We employed K-nearest neighbor (KNN) model as the base model for building the radiomics signature and clinical signature. Finally, a radiomics-clinical nomogram that combined intratumoral and peritumoral radiomics features as well as clinical features was developed. The prediction performance of each model was assessed by the area under the curve (AUC), sensitivity, specificity and calibration curve. Results: A total of 23 radiomics features were selected to develop radiomics models. The combined-region radiomics model showed favorable prediction efficiency in both the training dataset (AUC: 0.955) and the test dataset (AUC: 0.923). A radiomics-clinical nomogram was constructed and achieved excellent calibration and discrimination, which yielded an AUC value of 0.950, a sensitivity of 0.950 and a specificity of 0.920. Conclusions: This study proposed the nomogram that contributes to the accurate and intuitive identification of PTMC in ACR TI-RADS 3 nodules.
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Lung cancer is one of the most common malignant tumors in the world, of which non-small cell lung cancer (NSCLC) is the majority. The emergence of immune checkpoint inhibitors (ICIs) has greatly changed the treatment strategy of NSCLC and improved the prognosis of patients. However, in reality, only a small number of patients can achieve long-term benefit. Therefore, the identification of reliable predictive biomarkers is essential for the selection of treatment modalities. With the development of molecular biology and genome sequencing technology in recent years, as well as the in-depth understanding of tumor and its host immune microenvironment, research on biomarkers has emerged in an endless stream. This review focuses on the predictive biomarkers of immunotherapy efficacy in NSCLC, in order to provide some guidance for precision immunotherapy.â©.
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Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologiaRESUMO
BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.
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Antibacterianos , Infecções Comunitárias Adquiridas , Levofloxacino , Quinolonas , Humanos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Levofloxacino/uso terapêutico , Levofloxacino/efeitos adversos , Levofloxacino/administração & dosagem , Método Duplo-Cego , Antibacterianos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Adulto , Idoso , Resultado do Tratamento , Quinolonas/uso terapêutico , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Administração Intravenosa , Infusões Intravenosas , Adulto Jovem , Pneumonia/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Bacteriana/microbiologia , Idoso de 80 Anos ou maisRESUMO
PURPOSE: The Boston naming test (BNT), as a simple, fast, and easily administered neuropsychological test, was demonstrated to be useful in detecting language function. In this study, BNT was investigated whether it could be a screening tool for early postoperative cognitive dysfunction (POCD). METHODS: This prospective observational cohort study included 132 major noncardiac surgery patients and 81 nonsurgical controls. All participants underwent a mini-mental state examination (MMSE) and BNT 1 day before and 7 days after surgery. Early POCD was assessed by reliable change index and control group results. RESULTS: Seven days after surgery, among 132 patients, POCD was detected in 30 (22.7%) patients (95% CI, 15.5%-30.0%) based on MMSE, and 45 (34.1%) patients (95% CI, 26.3%-41.9%) were found with postoperative language function decline based on BNT and MMSE. Agreement between the BNT spontaneous naming and MMSE total scoring was moderate (Kappa .523), and the sensitivity of BNT spontaneous naming for detecting early POCD was .767. Further analysis showed that areas under receiver operating characteristics curves (AUC) did not show statistically significant differences when BNT spontaneous naming (AUC .862) was compared with MMSE language functional subtests (AUC .889), or non-language functional subtests (AUC .933). CONCLUSION: This study indicates the feasibility of implementing the BNT spontaneous naming test to screen early POCD in elderly patients after major noncardiac surgery.
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Despite the dominance of unsupervised and self-supervised anomaly detection methods in the current satellite fault diagnosis domain, supervised anomaly detection offers a superior alternative for high-sensitivity detection and lightweight deployment requirements specific to subsystems or components, such as attitude control systems (ACSs). This article addresses the issues of over-design and insufficient accuracy in the CNN network design for satellite ACS fault diagnosis by introducing the modified particle swarm optimization-advanced convolution blocks-based CNN (MPSO-ACBCNN) method. First, we present the ACBCNN, a lightweight, flexible-layer CNN architecture. This architecture leverages advanced convolution blocks (ACBs), which incorporate numerous efficient design elements to enhance feature extraction capabilities within power spectral density (PSD) graphs of various fault samples, and employs classical dense connection methods to prevent the issue of gradient vanishing. Second, we devise the MPSO-ACBCNN algorithm to optimize the ACBCNN fault diagnosis architecture for specified ACS using MPSO. In MPSO-ACBCNN, several optimizations to the canonical PSO are implemented, including the fitness design that balances the tradeoff between total parameter quantity and the training effectiveness, and methods to ensure feasible solutions, etc. Finally, numerical experimental results demonstrate the effectiveness and superiority of MPSO-ACBCNN in fault diagnosis for ACS.
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MicroRNAs have been studied extensively in neurodegenerative diseases. In a previous study, miR-153 promoted neural differentiation and projection formation in mouse hippocampal HT-22 cells. However, the pathways and molecular mechanism underlying miR-153-induced neural differentiation remain unclear. To explore the molecular mechanism of miR-153 on neural differentiation, we performed RNA sequencing on miR-153-overexpressed HT-22 cells. Based on RNA sequencing, differentially expressed genes (DEGs) and pathways in miR-153-overexpressed cells were identified. The Database for Annotation, Visualization and Integrated Discovery and Gene Set Enrichment Analysis were used to perform functional annotation and enrichment analysis of DEGs. Targetscan predicted the targets of miR-153. The Search Tool for the Retrieval of Interacting Genes and Cytoscape, were used to construct protein-protein interaction networks and identify hub genes. Q-PCR was used to detect mRNA expression of the identified genes. The expression profiles of the identified genes were compared between embryonic days 9.5 (E9.5) and E11.5 in the embryotic mouse brain of the GDS3442 dataset. Cell Counting Kit-8 assay was used to determine cell proliferation and cellular susceptibility to amyloid ß-protein (Aß) toxicity in miR-153-overexpressed cells. The results indicated that miR-153 increased cell adhesion/Ca2+ (Cdh5, Nrcam, and P2rx4) and Bdnf/Ntrk2 neurotrophic signaling pathway, and decreased ion channel activity (Kcnc3, Kcna4, Clcn5, and Scn5a). The changes in the expression of the identified genes in miR-153-overexpressed cells were consistent with the expression profile of GDS3442 during neural differentiation. In addition, miR-153 overexpression decreased cellular susceptibility to Aß toxicity in HT-22 cells. In conclusion, miR-153 overexpression may promote neural differentiation by inducing cell adhesion and the Bdnf/Ntrk2 pathway, and regulating electrophysiological maturity by targeting ion channels. MiR-153 may play an important role in neural differentiation; the findings provide a useful therapeutic direction for neurodegenerative diseases.
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BACKGROUND: Donation after circulatory death (DCD) heart transplantation (HTx) significantly expands the donor pool and reduces waitlist mortality. However, high-level evidence-based data on its safety and effectiveness are lacking. This meta-analysis aimed to compare the outcomes between DCD and donation after brain death (DBD) HTxs. METHODS: Databases, including MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials, were systematically searched for randomized controlled trials and observational studies reporting the outcomes of DCD and DBD HTxs published from 2014 onward. The data were pooled using random-effects models. Risk ratios (RRs) with 95% confidence intervals (CIs) were used as the summary measures for categorical outcomes and mean differences were used for continuous outcomes. RESULTS: Twelve eligible studies were included in the meta-analysis. DCD HTx was associated with lower 1-y mortality rate (DCD 8.13% versus DBD 10.24%; RRâ =â 0.75; 95% CI, 0.59-0.96; P â =â 0.02) and 5-y mortality rate (DCD 14.61% versus DBD 20.57%; RRâ =â 0.72; 95% CI, 0.54-0.97; P â =â 0.03) compared with DBD HTx. CONCLUSIONS: Using the current DCD criteria, HTx emerges as a promising alternative to DBD transplantation. The safety and feasibility of DCD hearts deserve further exploration and investigation.
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Transplante de Coração , Doadores de Tecidos , Humanos , Transplante de Coração/mortalidade , Transplante de Coração/efeitos adversos , Resultado do Tratamento , Morte Encefálica , Fatores de Risco , Sobrevivência de Enxerto , Fatores de Tempo , Seleção do Doador , Obtenção de Tecidos e Órgãos/métodos , Listas de Espera/mortalidade , Pessoa de Meia-Idade , Feminino , Masculino , AdultoRESUMO
Finding novel therapeutic modalities, improving drug delivery efficiency and targeting, and reducing the immune escape of tumor cells are currently hot topics in the field of tumor therapy. Bacterial therapeutics have proven highly effective in preventing tumor spread and recurrence, used alone or in combination with traditional therapies. In recent years, a growing number of researchers have significantly improved the targeting and penetration of bacteria by using genetic engineering technology, which has received widespread attention in the field of tumor therapy. In this paper, we provide an overview and assessment of the advancements made in the field of tumor therapy using genetically engineered bacteria. We cover three major aspects: the development of engineered bacteria, their integration with other therapeutic techniques, and the current state of clinical trials. Lastly, we discuss the limitations and challenges that are currently being faced in the utilization of engineered bacteria for tumor therapy.
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Bactérias , Engenharia Genética , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Animais , Bactérias/genética , Imunoterapia/métodos , Sistemas de Liberação de MedicamentosRESUMO
Thymic negative selection of the T cell receptor (TCR) repertoire is essential for establishing self-tolerance and acquired allograft tolerance following organ transplantation. However, it is unclear whether and how peripheral clonal deletion of alloreactive T cells induces transplantation tolerance. Here, we establish that programmed cell death protein 1 (PD-1) is a hallmark of alloreactive T cells and is associated with clonal expansion after alloantigen encounter. Moreover, we found that diphtheria toxin receptor (DTR)-mediated ablation of PD-1+ cells reshaped the TCR repertoire through peripheral clonal deletion of alloreactive T cells and promoted tolerance in mouse transplantation models. In addition, by using PD-1-specific depleting antibodies, we found that antibody-mediated depletion of PD-1+ cells prevented heart transplant rejection and the development of experimental autoimmune encephalomyelitis (EAE) in humanized PD-1 mice. Thus, these data suggest that PD-1 is an attractive target for peripheral clonal deletion and induction of immune tolerance.
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Deleção Clonal , Tolerância Imunológica , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1 , Animais , Receptor de Morte Celular Programada 1/imunologia , Camundongos , Deleção Clonal/imunologia , Tolerância Imunológica/imunologia , Humanos , Encefalomielite Autoimune Experimental/imunologia , Transplante de Coração , Linfócitos T/imunologia , Camundongos Knockout , Camundongos Endogâmicos BALB C , FemininoRESUMO
A photoredox-catalyzed unsymmetrical diamination of alkenes by using N-aminopyridinium salts and nitriles as the amination reagents has been developed. Various vicinal diamines were obtained in moderate to excellent yields under mild reaction conditions. Furthermore, this protocol could be applied in the late-stage modification of pharmaceuticals and natural products. Preliminary mechanistic studies suggested that this methodology may undergo a radical pathway followed by a Ritter-type reaction.
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Background and aims: The cachexia index (CXI) is a novel biomarker for estimating cancer cachexia. The cachexia index based on hand-grip strength (H-CXI) has been recently developed as a simple proxy for CXI. The present study aims to compare both the H-CXI and CXI for the prediction of cancer cachexia and postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. Methods: Patients who underwent radical operations for colorectal cancer were included in this study. Cancer cachexia was diagnosed according to the international consensus outlined by Fearon et al. The cachexia index (CXI) was calculated as [skeletal muscle index (SMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR)]. The H-CXI was calculated as [hand-grip strength (HGS)/height2 × serum albumin/NLR]. The SMI was measured based on the preoperative CT images at the third lumbar vertebra (L3) level. HGS was measured before surgery. Results: From July 2014 to May 2021, a total of 1,411 patients were included in the present study, of whom 361 (25.6%) were identified as having cancer cachexia. Patients with cachexia had a lower CXI (p < 0.001) and lower H-CXI (p < 0.001) than those without cachexia. A low CXI but not low H-CXI independently predicted cancer cachexia in the multivariate analysis (OR 1.448, p = 0.024). Both a low CXI (HR 1.476, p < 0.001 for OS; HR 1.611, p < 0.001 for DFS) and low H-CXI (HR 1.369, p = 0.007 for OS; HR 1.642, p < 0.001 for DFS) were independent predictors for overall survival (OS) and disease-free survival (DFS) after adjusting for the same covariates. A low H-CXI but not low CXI was an independent risk factor for postoperative complications (OR 1.337, p = 0.044). No significant association was found between cancer cachexia and postoperative complications. Conclusion: The CXI and H-CXI exhibited better prognostic value than cancer cachexia for the prediction of postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. The H-CXI was a superior index over the CXI in predicting short-term clinical outcomes, whereas the CXI demonstrated a closer correlation with Fearon's criteria for cancer cachexia. Ideal tools for the assessment of cancer cachexia should incorporate not only weight loss but also muscle mass, physical function, and inflammatory state.
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To enhance the specificity and sensitivity, cut the cost, and realize joint detection of multiple indicators, an immunoassay system based on the technology of time-resolved fluorescence resonance energy transfer (TR-FRET) was studied. Due to the FRET of the reagent, the donor probe and acceptor probe emitted specific fluorescence to enhance specificity. Long-lifetime specific fluorescence from the acceptor probe was combined with time-resolved technology to enhance sensitivity. A xenon flash lamp and a photomultiplier tube (PMT) were selected as the light source and detector, respectively. A filter-switching mechanism was placed in the light path, so the fluorescence signal from the donor and acceptor was measured alternately. The instrument's design is given, and some specificI parts are described in detail. Key technical specifications of the instrument and procalcitonin (PCT), C-reactive protein (CRP), and interleukin-6(IL-6) were tested, and the test results were presented subsequently. The CV value of the self-designed counting module is better than 0.01%, and the instrument noises for 620 nm and 665 nm are 41.44 and 10.59, respectively. When set at 37 °C, the temperature bias (B) is 0.06 °C, and the temperature fluctuation is 0.10 °C. The CV and bias are between ±3% and 5%, respectively, when pipetting volumes are between 10 µL and 100 µL. Within the concentration range of 0.01 nM to 10 nM, the luminescence values exhibit linear regression correlation coefficients greater than 0.999. For PCT detection, when the concentration ranges from 0.02 ng/mL to 50 ng/mL, the correlation coefficient of linear fitting exceeds 0.999, and the limit of quantification is 0.096 ng/mL. For CRP and IL-6, the detection concentration ranges from 0 ng/mL to 500 ng/mL and 0 ng/mL to 20 ng/mL, respectively, with limits of quantification of 2.70 ng/mL and 2.82 ng/mL, respectively. The experimental results confirm the feasibility of the technical and instrumental solutions.