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Efficient capture of 99TcO4- is the focus in nuclear waste management. For laboratory operation, ReO4- is used as a nonradioactive alternative to 99TcO4- to develop high-performance adsorbents for the treatment. However, the traditional design of new adsorbents is primarily driven by the chemical intuition of scientists and experimental methods, which are inefficient. Herein, a machine learning (ML)-assisted material genome approach (MGA) is proposed to precisely design high-efficiency adsorbents. ML models were developed to accurately predict adsorption capacity from adsorbent structures and solvent environment, thus predicting and screening the 2450 virtual pyridine polymers obtained by MGA, and it was found that halogen functionalization can enhance its adsorption efficiency. Two halogenated functional pyridine polymers (F-C-CTF and Cl-C-CTF) predicted by this approach were synthesized that exhibited excellent acid/alkali resistance and selectivity for ReO4-. The adsorption capacity reached 940.13 (F-C-CTF) and 732.74 mg g-1 (Cl-C-CTF), which were better than those of most reported adsorbents. The adsorption mechanism is comprehensively elucidated by experiment and density functional theory calculation, showing that halogen functionalization can form halogen-bonding interactions with 99TcO4-, which further justified the theoretical plausibility of the screening results. Our findings demonstrate that ML-assisted MGA represents a paradigm shift for next-generation adsorbent design.
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Exploring new high-performance anode materials is of great significance for next generation renewable energy technologies. Two-dimensional (2D) transition metal borides, named as MBenes, are receiving increasing attention in energy storage fields due to their structure-and-composition diversities and high electrical conductivities. Expanding the family of hexagonal MBenes to non-transition metal borides, we report two hexagonal IIA metal M2B2-typed MBenes and demonstrate the feasibility of exfoliation and application as anode materials for Li-ion batteries (LIBs) and Na-ion batteries (SIBs) using ab initio calculations. The predicted 2D Mg2B2 and Ca2B2 monolayers exhibit robust thermal and mechanical stabilities, inherent metallic properties, electrical conductivities, and excellent electrode performance. The outstanding theoretical specific capacities of Mg2B2 and Ca2B2 for Li/Na ions reach up to 764/527 and 859/527 mA h g-1, respectively. Furthermore, the average open-circuit voltages (OCVs) of Mg2B2 and Ca2B2 range from 0.275 to 0.395 V, indicating their suitability for anode materials. Additionally, the low diffusion energy barriers of Mg2B2 and Ca2B2 for Li/Na ions at delithiated/desodiated states (27/14 and 16/12 meV) and lithiated/sodiated states (187/58 and 52/34 meV) illustrate their excellent charge-discharge capabilities. These intriguing findings demonstrate the superior performance of the predicted IIA metal boride monolayers as promising anode materials for LIBs and SIBs and break through the limitations of transition metal MBenes as anode materials in terms of overall performance. Our study opens the door to the application of the main group metal MBenes in ion energy storage.
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Objective: To explore the association between circadian syndrome (CircS) and Metabolic Syndrome (MetS) with psoriasis. Compare the performance of MetS and CircS in predicting psoriasis. Methods: An observational study used data from the NHANES surveys conducted in 2005-2006 and 2009-2014. We constructed three multiple logistic regression models to investigate the relationship between MetS, CircS, and their components with psoriasis. The performance of MetS and CircS in predicting psoriasis was compared using five machine-learning algorithms, and the best-performing model was explained via SHAP. Then, bidirectional Mendelian randomization analyses with the inverse variance weighted (IVW) as the primary method were employed to determine the causal effects of each component. Result: A total of 9,531 participants were eligible for the study. Both the MetS (OR = 1.53, 95%CI: 1.07-2.17, P = 0.02) and CircS (OR = 1.40, 95%CI: 1.02-1.91, P = 0.039) positively correlated with psoriasis. Each CircS algorithmic model performs better than MetS, with Categorical Features+Gradient Boosting for CircS (the area under the precision-recall curve = 0.969) having the best prediction effect on psoriasis. Among the components of CircS, elevated blood pressure, depression symptoms, elevated waist circumference (WC), and short sleep contributed more to predicting psoriasis. Under the IVW methods, there were significant causal relationships between WC (OR = 1.52, 95%CI: 1.34-1.73, P = 1.35e-10), hypertension (OR = 1.68, 95%CI: 1.19-2.37, P = 0.003), depression symptoms (OR = 1.39, 95%CI: 1.17-1.65, P = 1.51e-4), and short sleep (OR = 2.03, 95%CI: 1.21-3.39, p = 0.007) with psoriasis risk. Conclusion: CircS demonstrated superior predictive ability for prevalent psoriasis compared to MetS, with elevated blood pressure, depression symptoms, and elevated WC contributing more to the prediction.
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Aprendizado de Máquina , Síndrome Metabólica , Inquéritos Nutricionais , Psoríase , Humanos , Síndrome Metabólica/epidemiologia , Psoríase/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Transtornos Cronobiológicos/epidemiologia , Transtornos Cronobiológicos/complicações , Idoso , Fatores de RiscoRESUMO
AIM OF THE STUDY: This study aimed to determine the effect of Epimedium brevicornu Maxim. (EF) on osteoporosis (OP) and its underlying molecular mechanisms, and to explore the existence of the "Gut-Bone Axis". MATERIAL AND METHODS: The impact of EF decoction (EFD) on OP was evaluated using istopathological examination and biochemical assays. Targeted metabolomics was employed to identify key molecules and explore their molecular mechanisms. Alterations in the gut microbiota (GM) were evaluated by 16S rRNA gene sequencing. The role of the GM was clarified using an antibiotic cocktail and faecal microbiota transplantation. RESULTS: EFD significantly increased the weight (14.06%), femur length (4.34%), abdominal fat weight (61.14%), uterine weight (69.86%), and insulin-like growth factor 1 (IGF-1) levels (59.48%), while reducing serum type I collagen cross-linked carboxy-terminal peptide (CTX-I) levels (15.02%) in osteoporotic mice. The mechanism of action may involve the regulation of the NLRP3/cleaved caspase-1/IL-1ß signalling pathway in improving intestinal tight junction proteins and bone metabolism. Additionally, EFD modulated the abundance of related GM communities, such as Lactobacillus, Coriobacteriaceae, bacteria of family S24-7, Clostridiales, and Prevotella, and increased propionate and butyrate levels. Antibiotic-induced dysbiosis of gut bacteria disrupted OP regulation of bone metabolism, which was restored by the recovery of GM. CONCLUSIONS: Our study is the first to demonstrate that EFD works in an OP mouse model by utilising GM and butyric acid. Thus, EF shows promise as a potential remedy for OP in the future.
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Caspase 1 , Epimedium , Microbioma Gastrointestinal , Interleucina-1beta , Proteína 3 que Contém Domínio de Pirina da Família NLR , Osteoporose , Transdução de Sinais , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Transdução de Sinais/efeitos dos fármacos , Caspase 1/metabolismo , Camundongos , Feminino , Interleucina-1beta/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Transplante de Microbiota FecalRESUMO
BACKGROUND: Our previous studies have shown that lipoxin A4 (LXA4) can serve as a potential biomarker for assessing the efficacy of exercise therapy in knee osteoarthritis (KOA), and fibroblast-like synoviocytes (FLSs) may play a crucial role in KOA pain as well as in the progression of the pathology. OBJECTIVE: By analyzing the GSE29746 dataset and collecting synovial samples from patients with different Kellgren-Lawrence (KL) grades for validation, we focused on exploring the potential effect of LXA4 on ferroptosis in FLSs through the ESR2/LPAR3/Nrf2 axis to alleviate pain and pathological advancement in KOA. METHODS: The association between FLSs ferroptosis and chondrocyte matrix degradation was explored by cell co-culture. We overexpressed and knocked down LPAR3 in vitro to explore its potential mechanism in FLSs. A rat model of monosodium iodoacetate (MIA)-induced KOA was constructed and intervened with moderate-intensity treadmill exercise and intraperitoneal injection of PHTPP to investigate the effects of the LXA4 intracellular receptor ESR2 on exercise therapy. RESULTS: ESR2, LPAR3, and GPX4 levels in the synovium decreased with increasing KL grade. After LXA4 intervention in the co-culture system, GPX4, LPAR3, and ESR2 were upregulated in FLSs, collagen II was upregulated in chondrocytes, and MMP3 and ADAM9 were downregulated. LPAR3 overexpression upregulated the expression of GPX4, Nrf2, and SOD1 in FLSs, while downregulating the expression of MMP13 and MMP3; LPAR3 knockdown reversed these changes. Moderate-intensity platform training improved the behavioral manifestations of pain in KOA rats, whereas PHTPP treatment partially reversed the improvement in synovial and cartilage pathologies induced by platform training. CONCLUSION: LXA4 inhibited FLSs ferroptosis by activating the ESR2/LPAR3/Nrf2 axis, thereby alleviating the pain and pathological progression of KOA. This study brings a new target for the treatment of KOA and also leads to a deeper understanding of the potential mechanisms of exercise therapy for KOA.
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Ferroptose , Lipoxinas , Fator 2 Relacionado a NF-E2 , Osteoartrite do Joelho , Sinoviócitos , Animais , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/terapia , Osteoartrite do Joelho/patologia , Ratos , Lipoxinas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Sinoviócitos/metabolismo , Humanos , Masculino , Modelos Animais de Doenças , Fibroblastos/metabolismo , Transdução de Sinais , Ratos Sprague-Dawley , Membrana Sinovial/metabolismo , Progressão da DoençaRESUMO
In this study, cobalt molybdate (CoMoO4) activated peracetic acid (PAA) was developed for water purification. CoMoO4/PAA system could remove 95% SMX with pseudo-first-order reaction rate constant of 0.15410 min-1, which was much higher than CoFe2O4/PAA, FeMoO4/PAA, and CoMoO4/persulfate systems. CoMoO4/PAA system follows a non-radical species pathway dominated by the high-valent cobalt (Co(IV)), and CH3C(O)OO⢠shows a minor contribution to decontamination. Density functional theory (DFT) calculation indicates that the generation of Co(IV) is thermodynamically more favorable than CH3C(O)OO⢠generation. The abundant Co(IV) generation was attributed to the special structure of CoMoO4 and effect of molybdenum on redox cycle of Co(II)/Co(III). DFT calculation showed that the atoms of SMX with higher ƒ0 and ƒ- values are the main attack sites, which are in accordance with the results of degradation byproducts. CoMoO4/PAA system can effectively reduce biological toxicity after the reaction. Benefiting from the selective of Co(IV) and CH3C(O)OOâ¢, the established CoMoO4/PAA system exhibits excellent anti-interference capacity and satisfactory decontamination performance under actual water conditions. Furthermore, the system was capable of good potential practical application for efficient removal of various organics and favorable reuse. Overall, this study provides a new strategy by CoMoO4 activated PAA for decontamination with high efficiency, high selectivity and favorable anti-interference.
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Background and Aims: Liver inflammation is important in guiding the initiation of antiviral treatment and affects the progression of chronic hepatitis B(CHB). The soluble programmed cell death 1 protein (sPD-1) was upregulated in inflammatory and infectious diseases and correlated with disease severity. We aimed to investigate the correlation between serum sPD-1 levels and liver inflammation in CHB patients and their role in indicating liver inflammation. Methods: 241 CHB patients who underwent liver biopsy were enrolled. The correlation between sPD-1 levels and the degree of liver inflammation was analyzed. Univariate and multivariate logistic regression analyses were performed to analyze independent variables of severe liver inflammation. Binary logistic regression analysis was conducted to construct a predictive model for severe liver inflammation, and the receiver operating characteristic curve (ROC) was used to evaluate the diagnostic accuracy of the predictive model. Results: sPD-1 was highest in CHB patients with severe liver inflammation, which was higher than that in CHB patients with mild or moderate liver inflammation (P < 0.001). Besides, sPD-1 was weakly correlated with AST (r = 0.278, P < 0.001). Multivariable analysis showed that sPD-1 was an independent predictor of severe liver inflammation. The predictive model containing sPD-1 had areas under the ROC (AUROCs) of 0.917 and 0.921 in predicting severe liver inflammation in CHB patients and CHB patients with ALT ≤ 1× upper limit of normal (ULN), respectively. Conclusions: Serum sPD-1 level is associated with liver inflammation in CHB patients, and high levels of sPD-1 reflect severe liver inflammation. Serum sPD-1 is an independent predictor of severe liver inflammation and shows improved diagnostic accuracy when combined with other clinical indicators.
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Artificial ion channel membranes hold high promise in water treatment, nanofluidics, and energy conversion, but it remains a great challenge to construct such smart membranes with both reversible ion-gating capability and desirable ion selectivity. Herein, we constructed a smart MXene-based membrane via p-phenylenediamine functionalization (MLM-PPD) with highly stable and aligned two-dimensional subnanochannels, which exhibits reversible ion-gating capability and ultrahigh metal ion selectivity similar to biological ion channels. The pH-sensitive groups within the MLM-PPD channel confers excellent reversible Mg2+-gating capability with a pH-switching ratio of up to 100. The mono/divalent metal-ion selectivity up to 1243.8 and 400.9 for K+/Mg2+ and Li+/Mg2+, respectively, outperforms other reported membranes. Theoretical calculations combined with experimental results reveal that the steric hindrance and stronger PPD-ion interactions substantially enhance the energy barrier for divalent metal ions passing through the MLM-PPD, and thus leading to ultrahigh mono/divalent metal-ion selectivity. This work provides a new strategy for developing artificial-ion channel membranes with both reversible ion-gating functionality and high-ion selectivity for various applications.
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Canais Iônicos , Metais , Nitritos , Elementos de Transição , Íons , Cátions Bivalentes , Membranas Artificiais , Concentração de Íons de HidrogênioRESUMO
BACKGROUND: Chronic shoulder pain is a common musculoskeletal problem associated with unreleased pain and functional dysfunction that can evolve into central sensitization. Some forms of manual therapy may exacerbate pain and central sensitization. This study investigated the impact of joint position sense therapy (JPST), a moderate joint proprioception training technique, on central sensitization, shoulder functional dysfunction, and pain in patients with chronic shoulder pain compared with more intense exercises or aggressive manual therapies. METHODS: We assessed the pressure pain threshold (PPT) in 30 patients with and 30 patients without chronic shoulder pain. The assessment focused on 4 muscle sites: deltoid, upper trapezius, brachioradialis, and tibialis anterior. Thirty patients with chronic shoulder pain were randomly divided into the JPST and control groups. The JPST group underwent additional shoulder joint position-sense training. The efficiency outcomes were the disabilities of the arm, shoulder, and hand questionnaire, visual analog scale (VAS), and PPT, evaluated at baseline and after the intervention. RESULTS: Significant differences were observed in the PPT values at the brachioradialis (Pâ <â .05), deltoid (Pâ <â .01), and trapezius (Pâ <â .001) among the non-chronic and chronic groups, but not in the tibialis anterior muscle (Pâ >â .05). Although both control and JPST interventions effectively improved the disabilities of the arm, shoulder, and hand questionnaire score, pain intensity, and PPT values in the upper limb, the outcomes in the JPST group were significantly different from those in the control group. CONCLUSIONS: Generalized hyperalgesia changes limited to the upper limbs were observed in patients with chronic shoulder pain. JPST has beneficial effects on pain control and functional dysfunction in patients with chronic shoulder pain.
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Sensibilização do Sistema Nervoso Central , Dor de Ombro , Humanos , Dor de Ombro/terapia , Extremidade Superior , Manejo da Dor , PropriocepçãoRESUMO
The intellectual property of deep networks can be easily "stolen" by surrogate model attack. There has been significant progress in protecting the model IP in classification tasks. However, little attention has been devoted to the protection of image processing models. By utilizing consistent invisible spatial watermarks, the work [1] first considered model watermarking for deep image processing networks and demonstrated its efficacy in many downstream tasks. Its success depends on the hypothesis that if a consistent watermark exists in all prediction outputs, that watermark will be learned into the attacker's surrogate model. However, when the attacker uses common data augmentation attacks (e.g., rotate, crop, and resize) during surrogate model training, it will fail because the underlying watermark consistency is destroyed. To mitigate this issue, we propose a new watermarking methodology, "structure consistency", based on which a new deep structure-aligned model watermarking algorithm is designed. Specifically, the embedded watermarks are designed to be aligned with physically consistent image structures, such as edges or semantic regions. Experiments demonstrate that our method is more robust than the baseline in resisting data augmentation attacks. Besides that, we test the generalization ability and robustness of our method to a broader range of adaptive attacks.
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BACKGROUND: The aim of this study was to investigate patient survival and factors associated with survival in second primary non-Hodgkin lymphoma (NHL) compared with the first primary NHL. METHODS: The retrospective cohort study used data from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2014. Demographic characteristics, histological types, Ann Arbor stage, and treatment information were collected. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for factors associated with overall survival (OS) and cancer-specific survival (CSS) in the first and second primary NHLs. RESULTS: Of 318,168 cases followed for 5 years, 299,248 patients developed the first primary NHL and 18,920 patients developed the second primary NHL. This study identified a rising incidence of first and second primary NHL from 2000 to 2014. For the second primary NHL, the OS risk was higher when compared to the first primary NHL (HR: 1.13, 95% CI: 1.11 to 1.15, P <0.001). Risk factors that negatively affected OS in the first primary NHL included being male, over 40 years of age, certain marital statuses, specific histological types, and advanced disease stages. In contrast, being of White race and having histological types such as Follicular Lymphoma (FL), Marginal Zone Lymphoma (MZL), and mantle B-cell NHL were associated with better OS outcomes. Treatments like surgery, radiation therapy, and chemotherapy were associated with a lower risk of OS and CSS in the first primary NHL. For the second primary NHL, the detrimental risk factors were similar but also included being over the age of 60. Certain histological types showed a lower OS risk relative to diffuse Large B-cell Lymphoma (DLBCL). While surgery and chemotherapy were beneficial for OS, radiation therapy did not improve survival in second primary NHL cases. Notably, undergoing chemotherapy for the first primary cancer increased the OS risk in the second primary NHL, whereas surgery and radiation seemed to offer a protective effect against OS risk in the second primary NHL (all P <0.05). CONCLUSION: Our findings emphasize the need for tailored strategies in managing the second primary NHL, given the distinct survival patterns and risk factor profiles compared to the first primary NHL. Future research should aim to further elucidate these differences to improve prognosis and treatment approaches for second primary NHL patients.
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Linfoma não Hodgkin , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Estudos de Coortes , Estudos Retrospectivos , Incidência , Programa de SEER , Linfoma não Hodgkin/terapia , Linfoma não Hodgkin/tratamento farmacológico , PrognósticoRESUMO
Background and objective: The brain-computer interface (BCI) system based on steady-state visual evoked potentials (SSVEP) is expected to help disabled patients achieve alternative prosthetic hand assistance. However, the existing study still has some shortcomings in interaction aspects such as stimulus paradigm and control logic. The purpose of this study is to innovate the visual stimulus paradigm and asynchronous decoding/control strategy by integrating augmented reality technology, and propose an asynchronous pattern recognition algorithm, thereby improving the interaction logic and practical application capabilities of the prosthetic hand with the BCI system. Methods: An asynchronous visual stimulus paradigm based on an augmented reality (AR) interface was proposed in this paper, in which there were 8 control modes, including Grasp, Put down, Pinch, Point, Fist, Palm push, Hold pen, and Initial. According to the attentional orienting characteristics of the paradigm, a novel asynchronous pattern recognition algorithm that combines center extended canonical correlation analysis and support vector machine (Center-ECCA-SVM) was proposed. Then, this study proposed an intelligent BCI system switch based on a deep learning object detection algorithm (YOLOv4) to improve the level of user interaction. Finally, two experiments were designed to test the performance of the brain-controlled prosthetic hand system and its practical performance in real scenarios. Results: Under the AR paradigm of this study, compared with the liquid crystal display (LCD) paradigm, the average SSVEP spectrum amplitude of multiple subjects increased by 17.41%, and the signal-noise ratio (SNR) increased by 3.52%. The average stimulus pattern recognition accuracy was 96.71 ± 3.91%, which was 2.62% higher than the LCD paradigm. Under the data analysis time of 2s, the Center-ECCA-SVM classifier obtained 94.66 ± 3.87% and 97.40 ± 2.78% asynchronous pattern recognition accuracy under the Normal metric and the Tolerant metric, respectively. And the YOLOv4-tiny model achieves a speed of 25.29fps and a 96.4% confidence in the prosthetic hand in real-time detection. Finally, the brain-controlled prosthetic hand helped the subjects to complete 4 kinds of daily life tasks in the real scene, and the time-consuming were all within an acceptable range, which verified the effectiveness and practicability of the system. Conclusion: This research is based on improving the user interaction level of the prosthetic hand with the BCI system, and has made improvements in the SSVEP paradigm, asynchronous pattern recognition, interaction, and control logic. Furthermore, it also provides support for BCI areas for alternative prosthetic control, and movement disorder rehabilitation programs.
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BACKGROUND: CD2-associated protein (CD2AP) is a podocyte-associated gene and its reduced expression is associated with the development of proteinuria and glomerulosclerosis. However, few studies have focused on the correlation between the expression and prognosis of CD2AP in renal clear cell carcinoma (ccRCC). Therefore, we aimed to assess the regulation of CD2AP expression and prognostic value in ccRCC. METHODS: Multiple databases were employed to examine the expression of CD2AP in ccRCC. RT-qPCR, Western Blot and immunohistochemistry were used to validate CD2AP expression in different cell lines and tissue samples. Kaplan-Meier analysis and ROC curve analysis were performed on the predictive prognostic performance of CD2AP. COX regression was used to construct CD2AP-related prognostic models. The TIMER and TISIDB databases were used to analyze the correlation of tumor-infiltrating immune cells with gene expression, mutations, somatic copy number variation, and immune molecules. Mass spectrometry was used to detect methylation status of the promoter CpG site of CD2AP in multiple cells. RESULTS: We found that CD2AP expression was downregulated in ccRCC and its lower expression level was correlation with worse patient prognosis, higher tumor stage and grade and distant metastasis through analysis of databases, ccRCC cell lines and clinical tissue samples. Moreover, database and mass spectrometry techniques identified and validated cg12968598 hypermethylation as one of the key reasons for the downregulation of CD2AP expression. CD2AP expression was also associated with macrophage and neutrophil infiltration. CONCLUSIONS: Taken together, our results suggest that CD2AP can be used as a diagnostic and prognostic biomarker in ccRCC patients and that DNA hypermethylation plays an important role in reducing CD2AP expression.
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Proteínas Adaptadoras de Transdução de Sinal , Carcinoma de Células Renais , Carcinoma , Proteínas do Citoesqueleto , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Variações do Número de Cópias de DNA , Prognóstico , Neoplasias Renais/genética , BiomarcadoresRESUMO
Notwithstanding the prominent performance shown in various applications, point cloud recognition models have often suffered from natural corruptions and adversarial perturbations. In this paper, we delve into boosting the general robustness of point cloud recognition, proposing Point-Cloud Contrastive Adversarial Training (PointCAT). The main intuition of PointCAT is encouraging the target recognition model to narrow the decision gap between clean point clouds and corrupted point clouds by devising feature-level constraints rather than logit-level constraints. Specifically, we leverage a supervised contrastive loss to facilitate the alignment and the uniformity of hypersphere representations, and design a pair of centralizing losses with dynamic prototype guidance to prevent features from deviating outside their belonging category clusters. To generate more challenging corrupted point clouds, we adversarially train a noise generator concurrently with the recognition model from the scratch. This differs from previous adversarial training methods that utilized gradient-based attacks as the inner loop. Comprehensive experiments show that the proposed PointCAT outperforms the baseline methods, significantly enhancing the robustness of diverse point cloud recognition models under various corruptions, including isotropic point noises, the LiDAR simulated noises, random point dropping, and adversarial perturbations. Our code is available at: https://github.com/shikiw/PointCAT.
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Immune checkpoints (ICPs) play a crucial role in regulating the immune response. In the tumor, malignant cells can hijack the immunosuppressive effects of inhibitory ICPs to promote tumor progression. Extracellular vesicles (EVs) are produced by a variety of cells and contain bioactive molecules on their surface or within their lumen. The expression of ICPs has also been detected in EVs. In vitro and in vivo studies have shown that extracellular vesicle immune checkpoints (EV ICPs) have immunomodulatory effects and are involved in tumor immunity. EV ICPs isolated from the peripheral blood of cancer patients are closely associated with the tumor progression and the prognosis of cancer patients. Blocking inhibitory ICPs has been recognized as an effective strategy in cancer treatment. However, the efficacy of immune checkpoint inhibitors (ICIs) in cancer treatment is hindered by the emergence of therapeutic resistance, which limits their widespread use. Researchers have demonstrated that EV ICPs are correlated with clinical response to ICIs therapy and were involved in therapeutic resistance. Therefore, it is essential to investigate the immunomodulatory effects, underlying mechanisms, and clinical significance of EV ICPs in cancer. This review aims to comprehensively explore these aspects. We have provided a comprehensive description of the cellular origins, immunomodulatory effects, and clinical significance of EV ICPs in cancer, based on relevant studies.
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Vesículas Extracelulares , Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Vesículas Extracelulares/imunologia , Neoplasias/imunologia , Neoplasias/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologia , Imunomodulação , Animais , Proteínas de Checkpoint Imunológico/metabolismo , Proteínas de Checkpoint Imunológico/genética , Imunoterapia/métodos , Microambiente Tumoral/imunologiaRESUMO
BACKGROUND: Therapies for diffuse large B-cell lymphoma (DLBCL) are limited due to the diverse gene expression profiles and complicated immune microenvironments, making it an aggressive lymphoma. Beyond this, researches have shown that ferroptosis contributes to tumorigenesis, progression, and metastasis. We thus are interested to dissect the connection between ferroptosis and disease status of DLBCL. We aim at generating a valuable prognosis gene signature for predicting the status of patients of DLBCL, with focus on ferroptosis-related genes (FRGs). OBJECTIVE: To examine the connection between ferroptosis-related genes (FRGs) and clinical outcomes in DLBCL patients based on public datasets. METHODS: An expression profile dataset for DLBCL was downloaded from GSE32918 (https://www.ncbi.nlm.nih.gov/geo/ query/acc.cgi?acc=gse32918), and a ferroptosis-related gene cluster was obtained from the FerrDb database (http://www. zhounan.org/ferrdb/). A prognostic signature was developed from this gene cluster by applying a least absolute shrinkage and selection operator (LASSO) Cox regression analysis to GSE32918, followed by external validation. Its effectiveness as a biomarker and the prognostic value was determined by a receiver operator characteristic curve mono factor analysis. Finally, functional enrichment was evaluated by the package Cluster Profiler of R. RESULTS: Five ferroptosis-related genes (FRGs) (GOP1, GPX2, SLC7A5, ATF4, and CXCL2) associated with DLBCL were obtained by a multivariate analysis. The prognostic power of these five FRGs was verified by TCGA (https://xenabrowser.net/datapages/?dataset=TCGA.DLBC.sampleMap%2FHiSeqV2_PANCAN&host=https%3A%2F%2Ftcga.xenahubs.net&removeHub=https%3A%2F%2Fxena.treehouse.gi.ucsc.edu%3A44) and GEO (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=gse 32918) datasets, with ROC analyses. KEGG and GO analyses revealed that upregulated genes in the high-risk group based on the gene signature were enriched in receptor interactions and other cancer-related pathways, including pathways related to abnormal metabolism and cell differentiation. CONCLUSION: The newly developed signature involving GOP1, GPX2, SLC7A5, ATF4, and CXCL2 has the potential to serve as a prognostic biomarker. Furthermore, our results provide additional support for the contribution of ferroptosis to DLBCL.
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Biomarcadores Tumorais , Ferroptose , Linfoma Difuso de Grandes Células B , Humanos , Ferroptose/genética , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/mortalidade , Prognóstico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica , Sistema y+ de Transporte de Aminoácidos/genética , Feminino , TranscriptomaRESUMO
OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.
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Dor Lombar , Modalidades de Fisioterapia , Humanos , Dor Lombar/reabilitação , Dor Lombar/terapia , Consenso , Ensaios Clínicos Controlados Aleatórios como Assunto , Feminino , Dor Aguda/terapia , Dor Aguda/reabilitação , MasculinoRESUMO
BACKGROUND: Numerous inflammatory skin diseases are associated with the gut microbiota. Studies of the association between gut microbiota and inflammatory skin diseases have yielded conflicting results owing to confounding factors, and the causal relationship between them remains undetermined. METHODS: Two-sample Mendelian randomization (MR) was used to examine the association between gut microbiota and four common inflammatory skin diseases: acne, psoriasis, urticaria and atopic dermatitis. The summary statistics of the gut microbiota from the largest available genome-wide association study meta-analysis (n = 13,266) conducted by the MiBioGen consortium along with the summary statistics of the four diseases were obtained from the FinnGen consortium. Causal relationships were assessed using the inverse variance weighted (IVW), weighted median, MR-Egger and maximum likelihood methods, and several sensitivity analyses were performed to ensure the accuracy of the results. Finally, reverse and multivariable MR analyses were performed to verify the robustness of the results. RESULTS: We found causal associations of Bacteroidaceae [odds ratio (OR), 2.25; 95% confidence interval (CI), 1.48-3.42; pivw = 0.0001], Allisonella (OR, 1.42; 95% CI, 1.18-1.70; pivw = 0.0002) and Bacteroides (OR, 2.25; 95% CI, 1.48-3.42; pivw = 0.0001) with acne, the Eubacterium fissicatena group with psoriasis (OR, 1.22; 95% CI, 1.10-1.35; pivw = 0.0002) and Intestinibacter with urticaria (OR, 1.28; 95% CI, 1.13-1.45; pivw = 0.0001). These results were corrected for a false discovery rate. Sensitivity analyses were performed to validate the robustness of the associations and reverse MR confirmed that the results were not influenced by the reverse effect. CONCLUSION: Our study revealed that some gut microbiota are risk factors for inflammatory skin diseases, providing new information on potential therapeutic targets. Additionally, a possible association with the gut-skin axis was confirmed. Further research is required to elucidate the mechanisms underlying these relationships.
Assuntos
Acne Vulgar , Dermatite Atópica , Microbioma Gastrointestinal , Análise da Randomização Mendeliana , Psoríase , Humanos , Microbioma Gastrointestinal/genética , Psoríase/microbiologia , Psoríase/genética , Acne Vulgar/microbiologia , Dermatite Atópica/microbiologia , Urticária/microbiologia , Estudo de Associação Genômica AmplaRESUMO
Studies on the Fe(VI)/S(IV) process have focused on improving the efficiency of emerging contaminants (ECs) degradation under alkaline conditions. However, the performance and mechanisms under varying pH levels remain insufficiently investigated. This tudy delved into the efficiency and mechanism of Fe(VI)/S(IV) process using sulfamethoxazole (SMX) and ibuprofen (IBU) as model contaminants. We found that pH was crucial in governing the generation of reactive species, and both Fe(V/IV) and SO4â¢- were identified in the reaction system. Specifically, an increase in pH favored the formation of SO4â¢-, while the formation of Fe(VI) to Fe(V/IV) became more significant at lower pH. At pH 3.2, Fe(III) resulting from the Fe(VI) self-decay reactedwith HSO3-to produce SO4â¢-and â¢OH. Under near-neutral conditions, the coexistance of Fe(V/IV) and SO4â¢- in abundance contributed to the optimal oxidation of both pollutants in the Fe(VI)/S(IV) process, with the removal exceeding 74% in 5 min. Competitive quenching experiments showed that the contributions of Fe(V/IV) to SMX and IBU destruction dimished, while the contributions of radicals increased with an increase in pH. However, this evolution was slower during SMX degradation compared to IBU degradation. A comprehensive understnding of pH as the key factor is essential for the optimization of the sulfite-activated Fe(VI) oxidation process in water treatment.
Assuntos
Ferro , Poluentes Químicos da Água , Purificação da Água , Compostos Férricos , Poluentes Químicos da Água/análise , Cinética , Oxirredução , Sulfametoxazol , Purificação da Água/métodos , IbuprofenoRESUMO
Heat shock proteins play crucial roles in various biochemical processes, encompassing protein folding and translocation. HSP90B1, a conserved member of the heat shock protein family, growing evidences have demonstrated that it might be closely associated with cancer development. In the present study, we employed multi-omics analyses and cohort validations to explore the dynamic expression of HSP90B1 in pan-cancer and comprehensively evaluate HSP90B1 as a novel biomarker that hold promise for precision cancer diagnostics and therapeutics. The results suggest HSP90B1 was highly expressed in various kinds of tumors, often correlating with a poor prognosis. Notably, methylation of HSP90B1 emerged as a protective factor in several cancer types. In immune infiltration analysis, the expression of HSP90B1 in most tumors showed a negative association with CD8 + T cells. HSP90B1 expression was positively correlated with microsatellite instability and tumor mutational burden. HSP90B1 expression was also discovered to be positively correlated with tumor metabolism, cell cycle-related pathways and the expression of immune checkpoint genes. The expression of HSP90B1 was mainly negatively correlated with immunostimulatory genes and positively correlated with immunosuppressive genes, as well as strongly correlated with chemokines and their receptor genes. In addition, the HSP90B1 inhibitor PU-WS13 demonstrated significant efficacy in suppressing cancer cell proliferation in both leukemic and solid tumor cells, and remarkably reduced the expression of the cancer cell surface immune checkpoint PD-L1. The single-cell RNA sequencing analysis further highlighted that HSP90B1 was significantly higher in tumor cells compared to surrounding cells, revealing a potential target therapeutic window. Taken together, HSP90B1 emerges as a promising avenue for breakthroughs in cancer diagnosis, prognosis and therapy. This study provides a rationale for HSP90B1 targeted cancer diagnosis and therapy in future.