Patient-derived tumor-like cell clusters for personalized chemo- and immunotherapies in non-small cell lung cancer.

Many patient-derived tumor models have emerged recently. However, their potential to guide personalized drug selection remains unclear. Here, we report patient-derived tumor-like cell clusters (PTCs) for non-small cell lung cancer (NSCLC), capable of conducting 100-5,000 drug tests within 10 days. We have established 283 PTC models with an 81% success rate. PTCs contain primary tumor epithelium self-assembled with endogenous stromal and immune cells and show a high degree of similarity to the original tumors in phenotypic and genotypic features. Utilizing standardized culture and drug-response assessment protocols, PTC drug-testing assays reveal 89% overall consistency in prospectively predicting clinical outcomes, with 98.1% accuracy distinguishing complete/partial response from progressive disease. Notably, PTCs enable accurate prediction of clinical outcomes for patients undergoing anti-PD1 therapy by combining cell viability and IFN-γ value assessments. These findings suggest that PTCs could serve as a valuable preclinical model for personalized medicine and basic research in NSCLC.

Sleep disturbance in Angelman syndrome patients.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by abnormal expression of the maternal ubiquitin protein ligase E3A gene (UBE3A). As one of the most challenging symptoms and important focuses of new treatment, sleep disturbance is reported to occur in 70-80% of patients with AS and has a serious impact on the lives of patients and their families. Although clinical studies and animal model studies have provided some clues, recent research into sleep disorders in the context of AS is still very limited. It is generally accepted that there is an interaction between neurodevelopment and sleep; however, there is no recognized mechanism for sleep disorders in AS patients. Accordingly, there are no aetiologically specific clinical treatments for AS-related sleep disorders. The most common approaches involve ameliorating symptoms through methods such as behavioural therapy and symptomatic pharmacotherapy. In recent years, preclinical and clinical studies on the targeted treatment of AS have emerged. Although precision therapy for restoring the UBE3A level and the function of its signalling pathways is inevitably hindered by many remaining obstacles, this approach has the potential to address AS-related sleep disturbance.

HO-1 upregulation promotes mitophagy-dependent ferroptosis in PM2.5-exposed hippocampal neurons.

Fine particulate matter (PM2.5) has been extensively implicated in the pathogenesis of neurodevelopmental disorders, but the underlying mechanism remains unclear. Recent studies have revealed that PM2.5 plays a role in regulating iron metabolism and redox homeostasis in the brain, which is closely associated with ferroptosis. In this study, the role and underlying mechanism of ferroptosis in PM2.5-induced neurotoxicity were investigated in mice, primary hippocampal neurons, and HT22 cells. Our findings demonstrated that exposure to PM2.5 could induce abnormal behaviors, neuroinflammation, and neuronal loss in the hippocampus of mice. These effects may be attributed to ferroptosis induced by PM2.5 exposure in hippocampal neurons. RNA-seq analysis revealed that the upregulation of iron metabolism-related protein Heme Oxygenase 1 (HO-1) and the activation of mitophagy might play key roles in PM2.5-induced ferroptosis in HT22 cells. Subsequent in vitro experiments showed that PM2.5 exposure significantly upregulated HO-1 in primary hippocampal neurons and HT22 cells. Moreover, PM2.5 exposure activated mitophagy in HT22 cells, leading to the loss of mitochondrial membrane potential, alterations in the expression of autophagy-related proteins LC3, P62, and mTOR, as well as an increase in mitophagy-related protein PINK1 and PARKIN. As a heme-degradation enzyme, the upregulation of HO-1 promotes the release of excess iron, genetically inhibiting the upregulation of HO-1 in HT22 cells could prevent both PM2.5-induced mitophagy and ferroptosis. Furthermore, pharmacological inhibition of mitophagy in HT22 cells reduced levels of ferrous ions and lipid peroxides, thereby preventing ferroptosis. Collectively, this study demonstrates that HO-1 mediates PM2.5-induced mitophagy-dependent ferroptosis in hippocampal neurons, and inhibiting mitophagy or ferroptosis may be a key therapeutic target to ameliorate neurotoxicity following PM2.5 exposure.

[Pseudomonas Aeruginosa Affects the Function of Pulmonary Vascular Endothelial Cells].

Objective To investigate the impact of Pseudomonas aeruginosa(PA) infection on the function of pulmonary vascular endothelial cells,and explore the mechanism of this bacterium in exacerbating lung inflammation in mice. Methods Two hours after human lung microvascular endothelial cell(HULEC-5a) were infected with the PA strain PAO1,the mRNA levels of autophagy-related gene 5(ATG5),6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3(PFKFB3),and calcium adhesion protein 5(CDH5) were determined by reverse transcription real-time fluorescent quantitative PCR(RT-qPCR).The protein levels of ATG5,PFKFB3,and vascular endothelial calcium adhesion protein(VE-cadherin) were detected by immunofluorescence.After the expression of ATG5 and PFKFB3 was respectively knocked down by small interfering RNA(siRNA),RT-qPCR was employed to measure the mRNA levels of ATG5,PFKFB3,and CDH5,and immunofluorescence to detect the protein levels of PFKFB3 and VE-cadherin.In addition,the lactate assay kit was used to determine the level of lactate in the cells.After mice were infected with PAO1,lung inflammation was assessed through histopathological section staining.Confocal microscopy was employed to capture and analyze fluorescence-labeled PFKFB3 and VE-cadherin in endothelial cells. Results Compared with the control group,the HULEC-5a cells infected with PAO1 showed up-regulated mRNA and protein levels of PFKFB3(all P<0.05),down-regulated mRNA level of CDH5(P=0.023),disrupted continuity and down-regulated protein level of VE-cadherin(P<0.001),and elevated lactate level(P=0.017).Compared with PAO1-infected HULEC-5a cells,knocking down PFKFB3 led to the up-regulated mRNA level of CDH5(P=0.043),lowered lactate level(P=0.047),and restored continuity of VE-cadherin;knocking down ATG5 led to up-regulated mRNA and protein levels of PFKFB3(P=0.013 and P=0.003),elevated lactate level(P=0.015),and down-regulated mRNA level of CDH5(P=0.020) and protein level of VE-cadherin(P=0.001).The HE staining results showed obvious red blood cell leakage,inflammatory cell infiltration,alveolar septal widening,and partial detachment of vascular endothelial cells in the alveoli of PA-infected mice.Immunofluorescence staining showed up-regulated expression of PFKFB3 and decreased fluorescence signal of VE-cadherin in endothelial cells of infected mice compared with normal mice. Conclusion PA may regulate the PFKFB3 pathway via AGT5 to disrupt the function of pulmonary vascular endothelial cells,thereby exacerbating the inflammation in the lungs of mice.

Nondestructive Determination of Epicarp Hardness of Passion Fruit Using Near-Infrared Spectroscopy during Storage.

The hardness of passion fruit is a critical feature to consider when determining maturity during post-harvest storage. The capacity of near-infrared diffuse reflectance spectroscopy (NIRS) for non-destructive detection of outer and inner hardness of passion fruit epicarp was investigated in this work. The passion fruits' spectra were obtained using a near-infrared spectrometer with a wavelength range of 10,000-4000 cm-1. The hardness of passion fruit's outer epicarp (F1) and inner epicarp (F2) was then measured using a texture analyzer. Moving average (MA) and mean-centering (MC) techniques were used to preprocess the collected spectral data. Competitive adaptive reweighted sampling (CARS), successive projection algorithm (SPA), and uninformative variable elimination (UVE) were used to pick feature wavelengths. Grid-search-optimized random forest (Grids-RF) models and genetic-algorithm-optimized support vector regression (GA-SVR) models were created as part of the modeling process. After MC preprocessing and CARS selection, MC-CARS-Grids-RF model with 7 feature wavelengths had the greatest prediction ability for F1. The mean square error of prediction set (RMSEP) was 0.166 gN. Similarly, following MA preprocessing, the MA-Grids-RF model displayed the greatest predictive performance for F2, with an RMSEP of 0.101 gN. When compared to models produced using the original spectra, the R2P for models formed after preprocessing and wavelength selection improved. The findings showed that near-infrared spectroscopy may predict the hardness of passion fruit epicarp, which can be used to identify quality during post-harvest storage.

Multi-level feature fusion and joint refinement for simultaneous object pose estimation and camera localization.

Object pose estimation and camera localization are critical in various applications. However, achieving algorithm universality, which refers to category-level pose estimation and scene-independent camera localization, presents challenges for both techniques. Although the two tasks keep close relationships due to spatial geometry constraints, different tasks require distinct feature extractions. This paper pays attention to a unified RGB-D based framework that simultaneously performs category-level object pose estimation and scene-independent camera localization. The framework consists of a pose estimation branch called SLO-ObjNet, a localization branch called SLO-LocNet, a pose confidence calculation process and object-level optimization. At the start, we obtain the initial camera and object results from SLO-LocNet and SLO-ObjNet. In these two networks, we design there-level feature fusion modules as well as the loss function to achieve feature sharing between two tasks. Then the proposed approach involves a confidence calculation process to determine the accuracy of object poses obtained. Additionally, an object-level Bundle Adjustment (BA) optimization algorithm is further used to improve the precision of these techniques. The BA algorithm establishes relationships among feature points, objects, and cameras with the usage of camera-point, camera-object, and object-point metrics. To evaluate the performance of this approach, experiments are conducted on localization and pose estimation datasets including REAL275, CAMERA25, LineMOD, YCB-Video, 7 Scenes, ScanNet and TUM RGB-D. The results show that this approach outperforms existing methods in terms of both estimation and localization accuracy. Additionally, SLO-LocNet and SLO-ObjNet are trained on ScanNet data and tested on 7 Scenes and TUM RGB-D datasets to demonstrate its universality performance. Finally, we also highlight the positive effects of fusion modules, loss function, confidence process and BA for improving overall performance.

Research on Human-Robot Collaboration Method for Parallel Robots Oriented to Segment Docking.

In the field of aerospace, large and heavy cabin segments present a significant challenge in assembling space engines. The substantial inertial force of cabin segments' mass often leads to unexpected motion during docking, resulting in segment collisions, making it challenging to ensure the accuracy and quality of engine segment docking. While traditional manual docking leverages workers' expertise, the intensity of the labor and low productivity are impractical for real-world applications. Human-robot collaboration can effectively integrate the advantages of humans and robots. Parallel robots, known for their high precision and load-bearing capacity, are extensively used in precision assembly under heavy load conditions. Therefore, human-parallel-robot collaboration is an excellent solution for such problems. In this paper, a framework is proposed that is easy to realize in production, using human-parallel-robot collaboration technology for cabin segment docking. A fractional-order variable damping admittance control and an inverse dynamics robust controller are proposed to enhance the robot's compliance, responsiveness, and trajectory tracking accuracy during collaborative assembly. This allows operators to dynamically adjust the robot's motion in real-time, counterbalancing inertial forces and preventing collisions between segments. Segment docking assembly experiments are performed using the Stewart platform in this study. The results show that the proposed method allows the robot to swiftly respond to interaction forces, maintaining compliance and stable motion accuracy even under unknown interaction forces.

Avenue to novel o-carboranyl boron compounds - reactivity study of o-carborane-fused aminoborirane towards organic azides.

Herein we report the reactivity study of o-carborane-fused bis(trimethylsilyl)aminoborirane towards three different types of organic azides, i.e., aryl, alkyl, and silyl azides. The reaction with ArN3 (Ar = 2,6-iPr2C6H4, 2,6-C6H3Cl2, 2,4,6-C6H2Br3, C6F5) resulted in the cycloaddition of ArN3 to the borirane BN unit accompanied by silyl migration. Conversely, in the reaction with BnN3, only the BnN3 : borirane 1 : 2 ring expansion product was obtained. Finally, the reaction with Me3SiN3 resulted in a formal nitrene insertion product under thermal conditions. All of the newly obtained o-carborane-fused BN-containing heterocycles were fully characterized, and the mechanism of these substituent-dependent reactions was studied using DFT calculations.

Copper-Induced In Vivo Gene Amplification in Budding Yeast.

In the biotechnological industry, multicopy gene integration represents an effective strategy to maintain a high-level production of recombinant proteins and to assemble multigene biochemical pathways. In this study, we developed copper-induced in vivo gene amplification in budding yeast for multicopy gene expressions. To make copper as an effective selection pressure, we first constructed a copper-sensitive yeast strain by deleting the CUP1 gene encoding a small metallothionein-like protein for copper resistance. Subsequently, the reporter gene fused with a proline-glutamate-serine-threonine-destabilized CUP1 was integrated at the δ sites of retrotransposon (Ty) elements to counter the copper toxicity at 100 µM Cu2+. We further demonstrated the feasibility of modulating chromosomal rearrangements for increased protein expression under higher copper concentrations. In addition, we also demonstrated a simplified design of integrating the expression cassette at the CUP1 locus to achieve tandem duplication under high concentrations of copper. Taken together, we envision that this method of copper-induced in vivo gene amplification would serve as a robust and useful method for protein overproduction and metabolic engineering applications in budding yeast.

PANoptosis: bridging apoptosis, pyroptosis, and necroptosis in cancer progression and treatment.

This comprehensive review explores the intricate mechanisms of PANoptosis and its implications in cancer. PANoptosis, a convergence of apoptosis, pyroptosis, and necroptosis, plays a crucial role in cell death and immune response regulation. The study delves into the molecular pathways of each cell death mechanism and their crosstalk within PANoptosis, emphasizing the shared components like caspases and the PANoptosome complex. It highlights the significant role of PANoptosis in various cancers, including respiratory, digestive, genitourinary, gliomas, and breast cancers, showing its impact on tumorigenesis and patient survival rates. We further discuss the interwoven relationship between PANoptosis and the tumor microenvironment (TME), illustrating how PANoptosis influences immune cell behavior and tumor progression. It underscores the dynamic interplay between tumors and their microenvironments, focusing on the roles of different immune cells and their interactions with cancer cells. Moreover, the review presents new breakthroughs in cancer therapy, emphasizing the potential of targeting PANoptosis to enhance anti-tumor immunity. It outlines various strategies to manipulate PANoptosis pathways for therapeutic purposes, such as targeting key signaling molecules like caspases, NLRP3, RIPK1, and RIPK3. The potential of novel treatments like immunogenic PANoptosis-initiated therapies and nanoparticle-based strategies is also explored.

MG53 protects against Coxsackievirus B3-induced acute viral myocarditis in mice by inhibiting NLRP3 inflammasome-mediated pyroptosis via the NF-κB signaling pathway.

Pyroptosis, a novel programmed cell death mediated by NOD-like receptor protein 3 (NLRP3) inflammasome, is a critical pathogenic process in acute viral myocarditis (AVMC). Mitsugumin 53 (MG53) is predominantly expressed in myocardial tissues and has been reported to exert cardioprotective effects through multiple pathways. Herein, we aimed to investigate the biological function of MG53 in AVMC and its underlying regulatory mechanism in pyroptosis. BALB/c mice and HL-1 cells were infected with Coxsackievirus B3 (CVB3) to establish animal and cellular models of AVMC. As inflammation progressed in the myocardium, we found a progressive decrease in myocardial MG53 expression, accompanied by a significant enhancement of cardiomyocyte pyroptosis. MG53 overexpression significantly alleviated myocardial inflammation, apoptosis, fibrosis, and mitochondrial damage, thereby improving cardiac dysfunction in AVMC mice. Moreover, MG53 overexpression inhibited NLRP3 inflammasome-mediated pyroptosis, reduced pro-inflammatory cytokines (IL-1ß/18) release, and suppressed NF-κB signaling pathway activation both in vivo and in vitro. Conversely, MG53 knockdown reduced cell viability, facilitated cell pyroptosis, and increased pro-inflammatory cytokines release in CVB3-infected HL-1 cells by promoting NF-κB activation. These effects were partially reversed by applying the NF-κB inhibitor BAY 11-7082. In conclusion, our results suggest that MG53 acts as a negative regulator of NLRP3 inflammasome-mediated pyroptosis in CVB3-induced AVMC, partially by inhibiting the NF-κB signaling pathway. MG53 is a promising candidate for clinical applications in AVMC treatment.

Early exercise intervention promotes myelin repair in the brains of ischemic rats by inhibiting the MEK/ERK pathway.

Our previous studies have shown that early exercise intervention after stroke increases neural activity and synaptic plasticity and promotes the recovery of nerve fiber bundle integrity in the brain. However, the effect of exercise on the repair of myelin in the brain and the related mechanism are still unclear. In this study, we randomly divided the rats into three groups. Before and after 28 days of intervention, body weight, nerve function, the infarct size, white matter fiber bundle integrity, and nerve myelin structure and function were observed by measuring body weight, analysis of modified neurological severity score, CatWalk gait analysis, MRI, luxol fast blue staining, immunofluorescence, and transmission electron microscopy. Changes in the expression of proteins in the MEK/ERK pathway were assessed. The results showed that early exercise intervention resulted in neurological recovery, decreased the infarct volume and increased nerve fiber integrity, the myelin coverage area, myelin basic protein (MBP) fluorescence intensity expression, and myelin thickness. Furthermore, the expression level of MBP was significantly increased after early exercise intervention, while the expression levels of p-MEK1/2 and p-ERK1/2 were significantly reduced. In the cell study, MBP expression levels were significantly higher in the oxygen and glucose deprivation and administration group.In summary, early exercise intervention after stroke can promote myelin repair by inhibiting the MEK/ERK signaling pathway.

Association Between Long-Term Exposure to Ambient Air Pollution and the Risk of Mild Cognitive Impairment in a Chinese Urban Area: A Case-Control Study.

Background: As a prodromal stage of dementia, significant emphasis has been placed on the identification of modifiable risks of mild cognitive impairment (MCI). Research has indicated a correlation between exposure to air pollution and cognitive function in older adults. However, few studies have examined such an association among the MCI population inChina. Objective: We aimed to explore the association between air pollution exposure and MCI risk from the Hubei Memory and Aging Cohort Study. Methods: We measured four pollutants from 2015 to 2018, 3 years before the cognitive assessment of the participants. Logistic regression models were employed to calculate odds ratios (ORs) to assess the relationship between air pollutants and MCI risk. Results: Among 4,205 older participants, the adjusted ORs of MCI risk for the highest quartile of PM2.5, PM10, O3, and SO2 were 1.90 (1.39, 2.62), 1.77 (1.28, 2.47), 0.56 (0.42, 0.75), and 1.18 (0.87, 1.61) respectively, compared with the lowest quartile. Stratified analyses indicated that such associations were found in both males and females, but were more significant in older participants. Conclusions: Our findings are consistent with the growing evidence suggesting that air pollution increases the risk of mild cognitive decline, which has considerable guiding significance for early intervention of dementia in the older population. Further studies in other populations and broader geographical areas are warranted to validate these findings.

The composition of phenolic compounds in Chinese olive (Canarium album L.) cultivars and their contribution to the anti-inflammatory properties of the cultivars.

Objective: This study aimed to explore the phenolic compounds (PCs) present in three Chinese olive (Canarium album L.) cultivars and the contribution of these PCs to the anti-inflammatory activities of the cultivars. Methods: Ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap/mass spectrometry (UPLC-Q-Exactive/MS) was used to identify and quantify the PCs present in three Chinese olive cultivars, "Na zhong," "Tan xiang," and "Xiang zhong". 2,2-diphenyl-1-picrylhydrazyl (DPPH); 2,2'-azinobis (3-ethylbenzothiazoline 6-sulfonate) (ABTS); and oxygen radical absorption capacity (ORAC) assays were used to assess the antioxidant activities of the PCs. Furthermore, we analyzed the anti-inflammatory action of these PCs using lipopolysaccharide (LPS)-induced RAW264.7 cells. Results: A total of 44 PCs were identified in the three cultivars. Of these, 17 PCs were previously unidentified in Chinese olive. Among the cultivars, the free phenolics (FPs) of "Tan xiang" showed the strongest antioxidant activity. All cultivars have shown significant inhibition of TNF-α and IL-6 production. Clustering correlation analysis showed galloyl-bis-HHDP-glucose and paeonol have significant anti-inflammatory ability in FPs. Quininic, galloylquinic acid, 4-hydroxycinnamic acid and gallic acid hexoside have shown significant inhibition of IL-6 production in BPs. Furthermore, gallic acid, catechin, syringic acid, and nobiletin exhibit negative correlation in FPs and positive correlation in BPs of cytokine production, while corilagin and methyl ellagic acid pentoside exhibited opposite correlation. Conclusion: In summary, this study contributed to the literature on PCs in Chinese olives and the potential health benefits of FPs and BPs.

CircUSP1 as a novel marker promotes gastric cancer progression via stabilizing HuR to upregulate USP1 and Vimentin.

Circular RNAs (circRNAs) play a crucial role in regulating various tumors. However, their biological functions and mechanisms in gastric cancer (GC) have not been well understood. Here, we discovered a stable cytoplasmic circRNA named circUSP1 (hsa_circ_000613) in GC. CircUSP1 upregulation in GC tissues was correlated with tumor size and differentiation. We observed that circUSP1 promoted GC growth and metastasis. Mechanistically, circUSP1 mainly interacted with the RRM1 domain of an RNA-binding protein (RBP) called HuR, stabilizing its protein level by inhibiting ß-TrCP-mediated ubiquitination degradation. The oncogenic properties of HuR mediated promotive effects of circUSP1 in GC progression. Moreover, we identified USP1 and Vimentin as downstream targets of HuR in post-transcriptional regulation, mediating the effects of circUSP1. The parent gene USP1 also enhanced the viability and mobility of GC cells. Additionally, tissue-derived circUSP1 could serve as an independent prognostic factor for GC, while plasma-derived circUSP1 showed promise as a diagnostic biomarker, outperforming conventional markers including serum alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 199 (CA19-9). Our study highlights that circUSP1 promotes GC progression by binding to and stabilizing oncogenic HuR, thereby facilitating the upregulation of USP1 and Vimentin at the post-transcriptional level. These findings suggest that circUSP1 could be a potential therapeutic target and a diagnostic and prognostic biomarker for GC.

Spatiotemporal evolution characteristics and driving forces of vegetation cover variations in the Chengdu-Chongqing region of China under the background of rapid urbanization.

The research on the spatiotemporal changes and driving factors of ecosystems in rapidly urbanizing regions has always been a topic of widespread concern. As the fourth pole of China's economic development, the research on the Chengdu-Chongqing region has reference significance for the urbanization process of developing countries such as India, Brazil, and South Africa.The normalized difference vegetation index (NDVI) has been widely applied in studies of plant and ecosystem changes. Based on MODIS NDVI data from 2001 to 2020 and meteorological data of the same period, this study reveals the evolution of NDVI in the Chengdu-Chongqing region from three aspects: the spatiotemporal variation characteristics of NDVI, the prediction of future trends in vegetation coverage, and the response of vegetation to climate change and human activities. During the period of plant growth, the mean NDVI achieved a value of 0.78, and the vegetation coverage rate is increasing year by year. According to the Hurst index, the future NDVI in Chengdu-Chongqing region will tend to decrease, and its trend is opposite to that of the past period of time. The Chengdu-Chongqing region vegetation positively affected by human activities is greater than those negatively affected, and in terms of vegetation degradation, the impact of human activities is greater than climate change.

Discovery of novel covalent inhibitors of DJ-1 through hybrid virtual screening.

Background: DJ-1 is a ubiquitously expressed protein with multiple functions. Its overexpression has been associated with the occurrence of several cancers, positioning DJ-1 as a promising therapeutic target for cancer treatment. Methods: To find novel inhibitors of DJ-1, we employed a hybrid virtual screening strategy that combines structure-based and ligand-based virtual screening on a comprehensive compound library. Results: In silico study identified six hit compounds as potential DJ-1 inhibitors that were assessed in vitro at the cellular level. Compound 797780-71-3 exhibited antiproliferation activity in ACHN cells with an IC50 value of 12.18 µM and was able to inhibit the Wnt signaling pathway. This study discovers a novel covalent inhibitor for DJ-1 and paves the way for further optimization.

Screening and early warning system for chronic obstructive pulmonary disease with obstructive sleep apnoea based on the medical Internet of Things in three levels of healthcare: protocol for a prospective, multicentre, observational cohort study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent respiratory diseases in China and impose significant burdens on the healthcare system. Moreover, the co-occurrence of COPD and OSA exacerbates clinical outcomes significantly. However, comprehensive epidemiological investigations in China remain scarce, and the defining characteristics of the population affected by COPD and OSA, alongside their intrinsic relationship, remain ambiguous. METHODS AND ANALYSIS: We present a protocol for a prospective, multicentre, observational cohort study based on a digital health management platform across three different healthcare tiers in five sites among Chinese patients with COPD. The study aims to establish predicative models to identify OSA among patients with COPD and to predict the prognosis of overlap syndrome (OS) and acute exacerbations of COPD through the Internet of Things (IoT). Moreover, it aims to evaluate the feasibility, effectiveness and cost-effectiveness of IoT in managing chronic diseases within clinical settings. Participants will undergo baseline assessment, physical examination and nocturnal oxygen saturation measuring. Specific questionnaires screening for OSA will also be administered. Diagnostic lung function tests and polysomnography will be performed to confirm COPD and OSA, respectively. All patients will undergo scheduled follow-ups for 12 months to record the changes in symptoms, lung functions and quality of life. Primary outcomes include the prevalence and characteristics of OS, while secondary outcomes encompass OS prognosis and the feasibility of the management model in clinical contexts. A total of 682 patients with COPD will be recruited over 12-24 months. ETHICS AND DISSEMINATION: The study has been approved by Peking University Third Hospital, and all study participants will provide written informed consent. Study results will be published in an appropriate journal and presented at national and international conferences, as well as relevant social media and various stakeholder engagement activities. TRIAL REGISTRATION NUMBER: NCT04833725.

Fully dispersed cobalt diatomic site with significantly improved Fenton-like catalysis performance for organic pollutant degradation.

A novel strategy for better catalytic performance in terms of precisely tuning the metal atom number of active centers is gradually getting attention. In this paper, the Co atom pair sites on N-doped porous carbon was engineered. The binuclear Co2 site structure was identified by aberration-corrected scanning transmission electron microscopy and X-ray absorption spectroscopy. As expected, the Co2NC display an outstanding Fenton-like catalysis activity in tetracycline degradation with turnover frequency exceeding 0.91 min-1 that is approximately 4 times higher than the conventional CoN4 site. The EPR tests indicated that the ROS strength stimulated by the binuclear site was much stronger than that of single site. Theoretical density functional theory calculations reveal that the optimized adsorption configuration is the O1 of peroxymonosulfate (PMS) interacting with two Co atoms, leading to stronger interaction effect and electron transfer for PMS comparing to single atom sites.

Hydroalkoxylation of Enamides Catalyzed by N-Heteroarenium Iodides.

A facile and novel N-heteroarenium iodide-catalyzed hydroalkoxylation of enamides has been described. The protocol provides easy access to N,O-acetals, which proved to be a versatile synthetic synthon. The hydrosulfonylation, hydroamination, and hydrophosphorylation products of enamide could be indirectly provided from N,O-acetals. The reaction mechanism was further investigated, which indicated that the hydroalkoxylation of enamides was driven by weak coordination between enamide and the contact ion pair of N-heteroarenium iodide.