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Background: Reduced cardiorespiratory fitness levels are associated with increased short-term complications after surgery, and potentially exert long-lasting effects on the postoperative lives, work and educational pursuits of patients. Currently, research suggests that lifestyle interventions, such as preoperative physical exercise undertaken by patients themselves, may improve patients' cardiopulmonary fitness and reduce post-operative complications. This study aims to investigate the effectiveness and feasibility of a remote medical supervision model for prehabilitation exercise in patients undergoing thoracoscopic lung tumour resection surgery. Methods/Design: All enrolled patients will participate in a 4-week pre-operative exercise intervention to improve their cardiorespiratory fitness. During this period, patients will wear wearable devices and exercise at home based on exercise prescriptions. The exercise prescription comprises aerobic exercise (three times a week or more), muscle strengthening exercise (twice a week or more), and respiratory muscle exercise (once a day). The primary aim is to investigate whether baseline VO2max could be improved following a 4-week preoperative exercise program. Secondary objectives include changes in forced expiratory volume in 1 s and forced vital capacity, degree of acceptance of the technology, quality of life, handgrip strength, postoperative complication rate and length of hospital stay. Discussion: This study aims to evaluate the influence of preoperative prehabilitation exercises in a telemedicine active supervision mode in patients undergoing thoracoscopic lung tumour resection. As such, results of this trial might have some impact on future implementations of group- and home-based prehabilitation exercises in lung cancers. Trial registration: This study was approved by the Medical Ethics Committee of Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology (approval number: TJ-IRB20220564) with registration at ClinicalTrials.gov (identifier: NCT05608759).
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Developing drug delivery systems capable of achieving deep tumor penetration is a challenging task, yet there is a significant demand for such systems in cancer treatment. Hitchhiking on tumor-derived extracellular vesicles (EVs) represents a promising strategy for enhancing drug penetration into tumors. However, the limited drug assembly on EVs restricts its further application. Here, we present a novel approach to efficiently attach antitumor drugs to EVs using an engineered cell membrane-based vector. This vector includes the AS1411 aptamer for tumor-specific targeting, the vesicular stomatitis virus glycoprotein (VSV-G) for tumor cell membrane fusion, and a photosensitizer as the therapeutic agent while ensuring optimal drug encapsulation and stability. Upon injection, photosensitizers are firstly transferred to the tumor cell membrane and subsequently piggybacked onto EVs with the inherent secretion process. By hitchhiking with EVs, photosensitizers can be transferred layer by layer deep into the solid tumors. The results suggest that this EVs-hitchhiking strategy enables photosensitizers to penetrate deeply into tumor tissue, thereby enhancing the efficacy of phototherapy. This study offers broad application prospects for delivering drugs deeply into tumor tissues.
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Grain weight and size are major traits targeted in breeding to improve wheat (Triticum aestivum L.) yield. Here, we find that the histone acetyltransferase GENERAL CONTROL NONDEREPRESSIBLE 5 (GCN5) physically interacts with the calmodulin-binding transcription factor CAMTA2 and regulates wheat grain size and weight. gcn5 mutant grains were smaller and contained less starch. GCN5 promoted the expression of the starch biosynthesis genes SUCROSE SYNTHASE 2 (Sus2) and STARCH-BRANCHING ENZYME Ic (SBEIc) by regulating H3K9ac and H3K14ac levels in their promoters. Moreover, immunoprecipitation followed by mass spectrometry (IP-MS) revealed that CAMTA2 physically interacts with GCN5. The CAMTA2-GCN5 complex activated Sus2 and SBEIc by directly binding to their promoters and depositing H3K9ac and H3K14ac marks during wheat endosperm development. camta2 knockout mutants exhibited similar phenotypes to gcn5 mutants, including smaller grains that contained less starch. In gcn5 mutants, transcripts of high molecular weight (HMW) Glutenin (Glu) genes were downregulated, leading to reduced HMW glutenin protein levels, gluten content, and sodium dodecyl sulfate (SDS) sedimentation volume. However, the association of GCN5 with Glu genes was independent of CAMTA2, since GCN5 enrichment on Glu promoters was unchanged in camta2 knockouts. Finally, we identified a CAMTA2-AH3 elite allele that corresponded with enhanced grain size and weight, serving as a candidate gene for breeding wheat varieties with improved grain weight.
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BACKGROUND: Alcohol use and abuse remain prevalent in China, though mounting evidence shows that even drinking in moderation is detrimental to health. While many countries' intake is on the decline, China's alcohol consumption is rising fast and is on the path to overtaking countries like the United States, even on a per capita level. OBJECTIVES: This paper aims to analyze the danger of lax enforcement of laws and regulations against alcohol use and abuse and underscores the imperative for effective health interventions to curb problematic alcohol consumption in China. RESULTS: Different from their Western counterparts, Chinese drinkers often consume more spirit with a high percentage of alcohol in social settings that encourage the "ganbei culture"-making toasts with alcohol filled to the brim and downed in one go to show respect-which perpetuates excessive drinking at a fast pace. Though the country has various laws and regulations in place to curb problematic alcohol consumption, like workplace drinking, their impacts are dismal. Considering that China has 1.4 billion people, the country's uncurbed alcohol consumption trend could have a detrimental effect on national strategic objectives like "Healthy China 2030" and international ones like the Sustainable Development Goals. To further compound the situation, prevalent campaigns promoted by liquor companies-like alcohol-infused coffee, chocolate, and ice cream-may groom young people to develop alcohol consumption habits, if not addictions, for generations to come. CONCLUSIONS: We developed the Framework of 5Vs of China's "Ganbei Culture to shed light on the issue, with the hope that it, along with the overarching insights of this paper, can assist health professionals and policymakers in better guarding and improving public health against the harms of alcohol use and abuse in China and beyond.
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Lung adenocarcinoma is the most common primary lung cancer seen in the world, and identifying genetic markers is essential for predicting the prognosis of lung adenocarcinoma and improving treatment outcomes. It is well known that alterations in circadian rhythms are associated with a higher risk of cancer. Moreover, circadian rhythms play a regulatory role in the human body. Therefore, studying the changes in circadian rhythms in cancer patients is crucial for optimizing treatment. The gene expression data and clinical data were sourced from TCGA database, and we identified the circadian clock-related genes. We used the obtained TCGA-LUAD data set to build the model, and the other 647 lung adenocarcinoma patients' data were collected from two GEO data sets for external verification. A risk score model for circadian clock-related genes was constructed, based on the identification of 8 genetically significant genes. Based on ROC analyses, the risk model demonstrated a high level of accuracy in predicting the overall survival times of lung adenocarcinoma patients in training folds, as well as external data sets. This study has successfully constructed a risk model for lung adenocarcinoma prognosis, utilizing circadian rhythm as its foundation. This model demonstrates a dependable capacity to forecast the outcome of the disease, which can further guide the relevant mechanism of lung adenocarcinoma and combine behavioral therapy with treatment to optimize treatment decision-making.
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Adenocarcinoma de Pulmão , Relógios Circadianos , Neoplasias Pulmonares , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/diagnóstico , Adenocarcinoma de Pulmão/patologia , Prognóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Relógios Circadianos/genética , Feminino , Masculino , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Ritmo Circadiano/genética , Pessoa de Meia-Idade , Bases de Dados GenéticasRESUMO
BACKGROUND: The volume measurement of intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) provides critical information for precise treatment of patients with spontaneous ICH but remains a big challenge, especially for IVH segmentation. However, the previously proposed ICH and IVH segmentation tools lack external validation and segmentation quality assessment. PURPOSE: This study aimed to develop a robust deep learning model for the segmentation of ICH and IVH with external validation, and to provide quality assessment for IVH segmentation. METHODS: In this study, a Residual Encoding Unet (REUnet) for the segmentation of ICH and IVH was developed using a dataset composed of 977 CT images (all contained ICH, and 338 contained IVH; a five-fold cross-validation procedure was adopted for training and internal validation), and externally tested using an independent dataset consisting of 375 CT images (all contained ICH, and 105 contained IVH). The performance of REUnet was compared with six other advanced deep learning models. Subsequently, three approaches, including Prototype Segmentation (ProtoSeg), Test Time Dropout (TTD), and Test Time Augmentation (TTA), were employed to derive segmentation quality scores in the absence of ground truth to provide a way to assess the segmentation quality in real practice. RESULTS: For ICH segmentation, the median (lower-quantile-upper quantile) of Dice scores obtained from REUnet were 0.932 (0.898-0.953) for internal validation and 0.888 (0.859-0.916) for external test, both of which were better than those of other models while comparable to that of nnUnet3D in external test. For IVH segmentation, the Dice scores obtained from REUnet were 0.826 (0.757-0.868) for internal validation and 0.777 (0.693-0.827) for external tests, which were better than those of all other models. The concordance correlation coefficients between the volumes estimated from the REUnet-generated segmentations and those from the manual segmentations for both ICH and IVH ranged from 0.944 to 0.987. For IVH segmentation quality assessment, the segmentation quality score derived from ProtoSeg was correlated with the Dice Score (Spearman r = 0.752 for the external test) and performed better than those from TTD (Spearman r = 0.718) and TTA (Spearman r = 0.260) in the external test. By setting a threshold to the segmentation quality score, we were able to identify low-quality IVH segmentation results by ProtoSeg. CONCLUSIONS: The proposed REUnet offers a promising tool for accurate and automated segmentation of ICH and IVH, and for effective IVH segmentation quality assessment, and thus exhibits the potential to facilitate therapeutic decision-making for patients with spontaneous ICH in clinical practice.
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OBJECTIVE: To develop and evaluate the predictive value of a simplified lung ultrasound (LUS) method for forecasting respiratory support in term infants. METHODS: This observational, prospective, diagnostic accuracy study was conducted in a tertiary academic hospital between June and December 2023. A total of 361 neonates underwent LUS examination within 1 h of birth. The proportion of each LUS sign was utilized to predict their respiratory outcomes and compared with the LUS score model. After identifying the best predictive LUS sign, simplified models were created based on different scan regions. The optimal simplified model was selected by comparing its accuracy with both the full model and the LUS score model. RESULTS: After three days of follow-up, 91 infants required respiratory support, while 270 remained healthy. The proportion of confluent B-lines demonstrated high predictive accuracy for respiratory support, with an area under the curve (AUC) of 89.1% (95% confidence interval [CI]: 84.5-93.7%). The optimal simplified model involved scanning the R/L 1-4 region, yielding an AUC of 87.5% (95% CI: 82.6-92.3%). Both the full model and the optimal simplified model exhibited higher predictive accuracy compared to the LUS score model. The optimal cut-off value for the simplified model was determined to be 15.9%, with a sensitivity of 76.9% and specificity of 91.9%. CONCLUSIONS: The proportion of confluent B-lines in LUS can effectively predict the need for respiratory support in term infants shortly after birth and offers greater reliability than the LUS score model.
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Pulmão , Valor Preditivo dos Testes , Ultrassonografia , Humanos , Recém-Nascido , Feminino , Estudos Prospectivos , Masculino , Pulmão/diagnóstico por imagem , Ultrassonografia/métodos , Respiração Artificial/métodos , Nascimento a Termo/fisiologia , SeguimentosRESUMO
Background: Despite widespread application of minimally invasive video-assisted thoracic surgery (VATS), postoperative pain following this procedure is still a constant clinical challenge. Serratus anterior plane (SAP) block is one of the regional analgesic techniques with promising outcomes. However, due to the limited duration of action, optimal analgesia is often not achieved with a single injection. We tested whether in patients who have been subjected to routine SAP block under preoperative anesthesia, the addition of a second SAP block 24 hours after surgery, improves quality of recovery, lowers postoperative opioid consumption, and reduces the prevalence of chronic pain. Methods: The present study is a single institutional, prospective, randomized, triple-blinded, placebo-controlled study. Ninety patients undergoing VATS from January 2022 to April 2022 were randomized at 1:1 ratio to receive ultrasound-guided second SAP block with 15 mL 0.375% ropivacaine (SAP block group) or 15 mL normal saline (control group) 24 hours after both groups received routine SAP block with 15 mL 0.375% ropivacaine. The primary outcome was quality of patient recovery, measured using 40-item quality of recovery questionnaire (QoR-40) at postoperative day 2 (POD 2). Secondary outcomes included: postoperative pain scores at rest, postoperative opioid consumptions, number of times that patient controlled analgesia (PCA) pump button was pressed, perioperative complications and adverse effects, prevalence of chronic pain at 2nd and 3rd month postoperatively, and length of hospital stay (LOS). Results: A total of 83 patients completed the study: 43 patients in SAP block group and 40 patients in the control group. The global QoR-40 scores on POD 2 and POD 3 were significantly higher among SAP block group patients (180.07±11.34, 182.09±8.20) compared with the control group (172.18±6.15, 177.50±6.94) (P=0.01, P=0.008) respectively. Postoperative pain scores, opioid consumptions and incidence of postoperative nausea and vomiting were significantly lower among patients in SAP block group versus control group. There were no statistically significant differences in perioperative complications and LOS between the two groups. The prevalence of chronic pain at the 2nd and 3rd month postoperatively for patients in SAP block group and control group was 16.3%, 14%, and 32.5%, 27.5% respectively. Conclusions: In patients undergoing VATS, application of ultrasound-guided second SAP block 24 hours after surgery improved postoperative quality of life, reduced opioid consumption and related side effects, and lowered the prevalence of chronic pain.
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We aimed to uncover the pathological mechanism of ischemic stroke (IS) using a combined analysis of untargeted metabolomics and proteomics. The serum samples from a discovery set of 44 IS patients and 44 matched controls were analyzed using a specific detection method. The same method was then used to validate metabolites and proteins in the two validation sets: one with 30 IS patients and 30 matched controls, and the other with 50 IS patients and 50 matched controls. A total of 105 and 221 differentially expressed metabolites or proteins were identified, and the association between the two omics was determined in the discovery set. Enrichment analysis of the top 25 metabolites and 25 proteins in the two-way orthogonal partial least-squares with discriminant analysis, which was employed to identify highly correlated biomarkers, highlighted 15 pathways relevant to the pathological process. One metabolite and seven proteins exhibited differences between groups in the validation set. The binary logistic regression model, which included metabolite 2-hydroxyhippuric acid and proteins APOM_O95445, MASP2_O00187, and PRTN3_D6CHE9, achieved an area under the curve of 0.985 (95% CI: 0.966-1) in the discovery set. This study elucidated alterations and potential coregulatory influences of metabolites and proteins in the blood of IS patients.
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Biomarcadores , AVC Isquêmico , Metabolômica , Proteômica , Humanos , Biomarcadores/sangue , Metabolômica/métodos , Proteômica/métodos , AVC Isquêmico/sangue , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos de Casos e ControlesRESUMO
Background: Neonatal sleep is pivotal for their growth and development, yet manual interpretation of raw images is time-consuming and labor-intensive. Quantitative Electroencephalography (QEEG) presents significant advantages in terms of objectivity and convenience for investigating neonatal sleep patterns. However, research on the sleep patterns of healthy neonates remains scarce. This study aims to identify QEEG markers that distinguish between different neonatal sleep cycles and analyze QEEG alterations across various sleep stages in relation to postmenstrual age. Methods: From September 2023 to February 2024, full-term neonates admitted to the neonatology department at the Obstetrics and Gynecology Hospital of Fudan University were enrolled in this study. Electroencephalographic (EEG) recordings were obtained from neonates aged 37-42 weeks, within 1-7 days post-birth. The ROC curve was employed to evaluate QEEG features related to amplitude, range EEG (rEEG), spectral density, and connectivity across different sleep stages. Furthermore, regression analyses were performed to investigate the association between these QEEG characteristics and postmenstrual age. Results: The alpha frequency band's spectral_diff_F3 emerged as the most potent discriminator between active sleep (AS) and quiet sleep (QS). In distinguishing AS from wakefulness (W), the theta frequency's spectral_diff_C4 was the most effective, whereas the delta frequency's spectral_diff_P4 excelled in differentiating QS from W. During AS and QS phases, there was a notable increase in entropy within the delta frequency band across all monitored brain regions and in the spectral relative power within the theta frequency band, correlating with postmenstrual age (PMA). Conclusion: Spectral difference showcases the highest discriminative capability across awake and various sleep states. The observed patterns of neonatal QEEG alterations in relation to PMA are consistent with the maturation of neonatal sleep, offering insights into the prediction and evaluation of brain development outcomes.
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BACKGROUND: The field of neonatal sleep analysis is burgeoning with devices that purport to offer alternatives to polysomnography (PSG) for monitoring sleep patterns. However, the majority of these devices are limited in their capacity, typically only distinguishing between sleep and wakefulness. This study aims to assess the efficacy of a novel wearable electroencephalographic (EEG) device, the LANMAO Sleep Recorder, in capturing EEG data and analyzing sleep stages, and to compare its performance against the established PSG standard. METHODS: The study involved concurrent sleep monitoring of 34 neonates using both PSG and the LANMAO device. Initially, the study verified the consistency of raw EEG signals captured by the LANMAO device, employing relative spectral power analysis and Pearson correlation coefficients (PCC) for validation. Subsequently, the LANMAO device's integrated automated sleep staging algorithm was evaluated by comparing its output with expert-generated sleep stage classifications. RESULTS: Analysis revealed that the PCC between the relative spectral powers of various frequency bands during different sleep stages ranged from 0.28 to 0.48. Specifically, the correlation for delta waves was recorded at 0.28. The automated sleep staging algorithm of the LANMAO device demonstrated an overall accuracy of 79.60â¯%, Cohen kappa of 0.65, and F1 Score of 76.93â¯%. Individual accuracy for Wake at 87.20â¯%, NREM at 85.70â¯%, and REM Sleep at 81.30â¯%. CONCLUSION: While the LANMAO Sleep Recorder's automated sleep staging algorithm necessitates further refinement, the device shows promise in accurately recording neonatal EEG during sleep. Its potential for minimal invasiveness makes it an appealing option for monitoring sleep conditions in newborns, suggesting a novel approach in the field of neonatal sleep analysis.
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Eletroencefalografia , Polissonografia , Humanos , Recém-Nascido , Eletroencefalografia/métodos , Eletroencefalografia/instrumentação , Polissonografia/métodos , Polissonografia/instrumentação , Masculino , Feminino , Fases do Sono/fisiologia , Dispositivos Eletrônicos Vestíveis , Sono/fisiologia , Processamento de Sinais Assistido por Computador , AlgoritmosRESUMO
As a prevalent neurodegenerative disorder, Parkinson's disease is associated with oxidative stress. Our recent investigations revealed that reactive oxygen species (ROS) and PD-toxins like 6-hydroxydopamine (6-OHDA) can induce neuronal apoptosis through over-activation of Akt signaling. Chlorogenic acid (CGA), a natural acid phenol abundant in the human diet, is well-documented for its ability to mitigate intracellular ROS. In this study, we utilized CGA to treat experimental models of PD both in vitro and in vivo. Our study results demonstrated that SH-SY5Y and primary neurons exhibited cell apoptosis in response to 6-OHDA. Pretreatment with CGA significantly attenuated PD toxins-induced large amount of ROS, inhibiting Erk1/2 activation, preventing Akt inhibition, and hindering neuronal cell death. Combining the Erk1/2 inhibitor U0126 with CGA could reverse 6-OHDA-induced Akt inhibition, ROS, and apoptosis in the cells. Crucially, the Akt activator SC79 and ROS scavenger NAC both could eliminate excessive ROS via Akt and Erk1/2 signaling pathways, and CGA further potentiated these effects in PD models. Behavioral experiments revealed that CGA could alleviate gait abnormalities in PD model mice. The neuroprotective effects have been demonstrated in several endocrine regions and in the substantia nigra tissue, which shows the positive tyrosine hydroxylase (TH). Overall, our results suggest that CGA prevents the activation of Erk1/2 and inactivation of Akt by removing excess ROS in PD models. These findings propose a potential strategy for mitigating neuronal degeneration in Parkinson's disease by modulating the Akt/Erk1/2 signaling pathway through the administration of CGA and/or the use of antioxidants to alleviate oxidative stress.
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Apoptose , Ácido Clorogênico , Sistema de Sinalização das MAP Quinases , Neurônios , Fármacos Neuroprotetores , Estresse Oxidativo , Doença de Parkinson , Proteínas Proto-Oncogênicas c-akt , Espécies Reativas de Oxigênio , Ácido Clorogênico/farmacologia , Animais , Apoptose/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Oxidopamina , Masculino , Nitrilas/farmacologia , Modelos Animais de Doenças , Butadienos/farmacologiaRESUMO
Herein, we present a high efficiency system based on biochar loaded with layered manganese dioxide to remove tetracycline and heavy metals from livestock wastewater. Under the optimal conditions, the degradation efficiencies of TC in the δ-MnO2/BC/PS system were 85.5% at 25 °C and 38.5% at 5 °C. Radical quenching experiments revealed that radical reactions in the δ-MnO2/BC/PS system were weak under 15 °C. Adsorption degradation experiments showed that the system maintained good adsorption performance at 5 °C. Galvanic cell experiments and cyclic voltammetry showed that the δ-MnO2/BC material had good electrochemical activity and high stability in response to temperature, indicating that TC was degraded by a nonradical pathway that was not limited by temperature, such as electron transfer. Copper ion was important coadsorbent and coactivator of the reaction system. Furthermore, FTIR, XPS, and X-ray diffraction (XRD) analyses showed that Cu(II) in the system was involved in changing the manganese valence state in the δ-MnO2/BC material and increasing the -OH content of BC. Comparison of the different products generated during metabolic testing revealed that the reaction pathway of the system at low temperature (5 °C) differed from that at normal temperature (25 °C). The δ-MnO2/BC material demonstrated good removal ability for antibiotics and heavy metals at normal and low temperatures in actual biogas slurry. The study provides insight for improving the efficiency of environmentally friendly treatments of aquaculture wastewater in cold regions, which is of great significance for resource utilization.
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Antibacterianos , Carvão Vegetal , Cobre , Compostos de Manganês , Metais Pesados , Óxidos , Eliminação de Resíduos Líquidos , Águas Residuárias , Poluentes Químicos da Água , Compostos de Manganês/química , Águas Residuárias/química , Poluentes Químicos da Água/química , Óxidos/química , Carvão Vegetal/química , Cobre/química , Metais Pesados/química , Adsorção , Antibacterianos/química , Eliminação de Resíduos Líquidos/métodos , Sulfatos/química , Temperatura Baixa , TemperaturaRESUMO
BACKGROUND: Establishing causal relationships between metabolic biomarkers and neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD) is a challenge faced by observational studies. In this study, our aim was to investigate the causal associations between plasma metabolites and neurodegenerative diseases using Mendelian Randomization (MR) methods. METHODS: We utilized genetic associations with 1400 plasma metabolic traits as exposures. We used large-scale genome-wide association study (GWAS) summary statistics for AD and PD as our discovery datasets. For validation, we performed repeated analyses using different GWAS datasets. The main statistical method employed was inverse variance-weighted (IVW). We also conducted enrichment pathway analysis for IVW-identified metabolites. RESULTS: In the discovered dataset, there are a total of 69 metabolites (36 negatively, 33 positively) potentially associated with AD, and 47 metabolites (24 negativelyï¼ 23 positively) potentially associated with PD. Among these, 4 significant metabolites overlap with significant metabolites (PIVW < 0.05)in the validation dataset for AD, and 1 metabolite overlaps with significant metabolites in the validation dataset for PD. Three metabolites serve as common potential metabolic markers for both AD and PD, including Tryptophan betaine, Palmitoleoylcarnitine (C16:1), and X-23655 levels. Further pathway enrichment analysis suggests that the SLC-mediated transmembrane transport pathway, involving tryptophan betaine and carnitine metabolites, may represent potential intervention targets for treating AD and PD. CONCLUSION: This study offers novel insights into the causal effects of plasma metabolites on degenerative diseases through the integration of genomics and metabolomics. The identification of metabolites and metabolic pathways linked to AD and PD enhances our comprehension of the underlying biological mechanisms and presents promising targets for future therapeutic interventions in AD and PD.
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Biomarcadores , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Doença de Parkinson , Humanos , Doença de Parkinson/sangue , Doença de Parkinson/genética , Biomarcadores/sangue , Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Doenças Neurodegenerativas/sangue , Doenças Neurodegenerativas/genética , MetabolômicaRESUMO
PURPOSE: This paper is to offer insights for designing research utilizing Olink technology to identify biomarkers and potential therapeutic targets for disease treatment. EXPERIMENTAL DESIGN: We discusses the application of Olink technology in oncology, cardiovascular, respiratory and immune-related diseases, and Outlines the advantages and limitations of Olink technology. RESULTS: Olink technology simplifies the search for therapeutic targets, advances proteomics research, reveals the pathogenesis of diseases, and ultimately helps patients develop precision treatments. CONCLUSIONS: Although proteomics technology has been rapidly developed in recent years, each method has its own disadvantages, so in the future research, more methods should be selected for combined application to verify each other.
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Recently, due to physical aging, diseases, accidents, and other factors, the population with lower limb disabilities has been increasing, and there is consequently a growing demand for wheelchair products. Modern product design tends to be more intelligent and multi-functional than in the past, with the popularization of intelligent concepts. This supports the design of a new, fully functional, intelligent wheelchair that can assist people with lower limb disabilities in their day-to-day life. Based on the UCD (user-centered design) concept, this study focused on the needs of people with lower limb disabilities. Accordingly, the demand for different functions of intelligent wheelchair products was studied through a questionnaire survey, interview survey, literature review, expert consultation, etc., and the function and appearance of the intelligent wheelchair were then defined. A brain-machine interface system was developed for controlling the motion of the intelligent wheelchair, catering to the needs of disabled individuals. Furthermore, ergonomics theory was used as a guide to determine the size of the intelligent wheelchair seat, and eventually, a new intelligent wheelchair with the features of climbing stairs, posture adjustment, seat elevation, easy interaction, etc., was developed. This paper provides a reference for the design upgrade of the subsequently developed intelligent wheelchair products.
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Interfaces Cérebro-Computador , Estudos de Viabilidade , Cadeiras de Rodas , Humanos , Pessoas com Deficiência , Desenho de Equipamento , Ergonomia/métodos , Design Centrado no Usuário , Inquéritos e QuestionáriosRESUMO
Introduction: Objective: this study investigated the effect of sunlight on vitamin D and hemoglobin levels among the residents of Ningbo, China. The impact of gender, age, and season on vitamin D and hemoglobin levels was also explored. Methods: a total of 8,481 research subjects, including 5,146 men and 3,335 women, who were permanent residents of Ningbo and received health checkups at Ningbo Second Hospital, were included in the study. Ningbo City climate bulletin data from 2019 to 2022 was also included. Results: the study subjects received an average of 132.20 ± 40.05 h of sunlight exposure per month and had average vitamin D levels of 19.63 ± 6.61 ng/ml. Hemoglobin levels were adequate in 85.4 % of the participants and deficient in 14.6 %. Sunlight exposure correlated positively with vitamin D and negatively with hemoglobin levels. Regression analysis indicated that gender, age, and season affected vitamin D and hemoglobin levels to different degrees. Conclusion: in Ningbo, vitamin D deficiency was common in adults while hemoglobin levels were mostly normal. The amount of sunlight exposure had a significant effect on vitamin D and hemoglobin levels and this relationship was impacted by gender, age, and season.
Introducción: Objetivo: este estudio investigó el efecto de la luz solar sobre los niveles de vitamina D y hemoglobina entre los residentes de Ningbo, China. También se exploró el impacto del género, la edad y la estación del año en los niveles de vitamina D y hemoglobina. Métodos: se incluyeron en el estudio un total de 8481 sujetos de investigación, incluidos 5146 hombres y 3335 mujeres, que eran residentes permanentes de Ningbo y recibieron controles médicos en el Segundo Hospital de Ningbo. También se incluyeron datos del boletín climático de la ciudad de Ningbo de 2019 a 2022. Resultados: los sujetos del estudio recibieron un promedio de 132,20 ± 40,05 h de exposición solar al mes y tuvieron niveles promedio de vitamina D de 19,63 ± 6,61 ng/ml. Los niveles de hemoglobina fueron adecuados en el 85,4 % de los participantes y deficientes en el 14,6 %. La exposición a la luz solar se correlacionó positivamente con la vitamina D y negativamente con los niveles de hemoglobina. El análisis de regresión indicó que el género, la edad y la estación del año afectaron los niveles de vitamina D y hemoglobina en diferentes grados. Conclusión: en Ningbo, la deficiencia de vitamina D era común en los adultos, mientras que los niveles de hemoglobina eran en su mayoría normales. La cantidad de exposición a la luz solar tuvo un efecto significativo sobre los niveles de vitamina D y hemoglobina y esta relación se vio afectada por el género, la edad y la estación del año.
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Hemoglobinas , Estações do Ano , Luz Solar , Deficiência de Vitamina D , Vitamina D , Humanos , Masculino , Feminino , China/epidemiologia , Vitamina D/sangue , Hemoglobinas/análise , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/sangue , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Fatores Sexuais , Adolescente , Fatores EtáriosRESUMO
Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule IL17 inhibitors have previously been described. Herein, we report the discovery of a novel class of small molecule IL17A inhibitors, identified via a DNA-encoded chemical library screen, and their subsequent optimization to provide in vivo efficacious inhibitors. These new protein-protein interaction (PPI) inhibitors bind in a previously undescribed mode in the IL17A protein with two copies binding symmetrically to the central cavities of the IL17A homodimer.
Assuntos
DNA , Descoberta de Drogas , Interleucina-17 , Bibliotecas de Moléculas Pequenas , Interleucina-17/metabolismo , Interleucina-17/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , DNA/metabolismo , DNA/química , Humanos , Animais , Relação Estrutura-Atividade , Ligação Proteica , CamundongosRESUMO
Organophosphate esters (OPEs) have garnered significant attention in recent years. In view of the enormous ecosystem services value and severe degradation of coral reefs in the South China Sea, this study investigated the occurrence, distribution, and bioaccumulation of 11 OPEs in five coral regions: Daya Bay (DY), Weizhou Island (WZ), Sanya Luhuitou (LHT), Xisha (XS) Islands, and Nansha (NS) Islands. Although OPEs were detected at a high rate, their concentration in South China Sea seawater (1.56 ± 0.89 ng L-1) remained relatively low compared to global levels. All OPEs were identified in coral tissues, with Luhuitou (575 ± 242 ng g-1 dw) showing the highest pollution levels, attributed to intense human activities. Coral mucus, acting as a defense against environmental stresses, accumulated higher ∑11OPEs (414 ± 461 ng g-1 dw) than coral tissues (412 ± 197 ng g-1 dw) (nonparametric test, p < 0.05), and their compositional characteristics varied greatly. In the case of harsh aquatic environments, corals increase mucus secretion and then accumulate organic pollutants. Tissue-mucus partitioning varied among coral species. Most OPEs were found to be bioaccumulative (BAFs >5000 L kg-1) in a few coral tissue samples besides Triphenyl phosphate (TPHP). Mucus' role in the bioaccumulation of OPEs in coral shouldn't be ignored.