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Abstract Despite the growing recognition of the importance of street vendors and informal markets for urban life and the economy globally, research attention has tended to focus on essential products such as food or clothes and paid less attention to cultural products, such as antiques where potential gender, and other socio-demographic, differences in vending and buying behaviours may systematically differ. To explore these issues, this study employed spatial–temporal behaviour mapping (STBM) and field observations (n = 8587) at Beijing’s Panjiayuan antiques “ghost market” a term reflecting its previously illegal/underground and mobile nature. We monitored four representative sites within the market, four times a day for six consecutive days. The data included five categories of behaviour, four age groups, and two genders. Data were recorded and analysed using ArcGIS. Results showed that, unlike common marketplaces, the antique market is primarily frequented by male vendors and buyers, replicating patterns seen in ancient Chinese paintings of men being involved in the trading of “non-essentials”. Nonetheless, we found differing gender balances depending on the time and day of the week, different age groups, and spatial settings in different market areas. We summarise the nuanced relationships between the emerging gender spatio-temporal behaviour patterns and three key factors, spatial characteristics, physical activities and the social division of labour, in the Chinese context. The study reveals how the varied spatial–temporal patterns of a large antique “ghost market” raise long-established issues of equity and inclusivity and provide empirical insights that could inform decision-making and urban planning, such as better use of dynamic lighting provision to encourage a more gender-balanced experience.

Endothelial-to-mesenchymal transition (EndMT) is a pivotal event in diabetic retinopathy (DR). This study explored the role of circRNA zinc finger protein 532 (circZNF532) in regulating EndMT in DR progression. Human retinal microvascular endothelial cells (HRMECs) were exposed to high glucose (HG) to induce the DR cell model. Actinomycin D-treated HRMECs were used to confirm the mRNA stability of phosphoinositide-3 kinase catalytic subunit δ (PIK3CD). The interaction between TATA-box-binding protein-associated factor 15 (TAF15) and circZNF532/PIK3CD was subsequently analyzed using RNA immunoprecipitation (RIP), RNA pull-down. It was found that HG treatment accelerated EndMT process, facilitated cell migration and angiogenesis, and enhanced PIK3CD and p-AKT levels in HRMECs, whereas si-circZNF532 transfection neutralized these effects. Further data showed that circZNF532 recruited TAF15 to stabilize PIK3CD, thus elevating PIK3CD expression. Following rescue experiments suggested that PIK3CD overexpression partially negated the inhibitory effect of circZNF532 silencing on EndMT, migration, and angiogenesis of HG-treated HRMECs. In conclusion, our results suggest that circZNF532 recruits TAF15 to stabilize PIK3CD, thereby facilitating EndMT in DR.

Urinary cell-free DNA (UcfDNA) is gaining recognition as an important biomarker for diagnosing bladder cancer. UcfDNA contains tumor derived DNA sequences, making it a viable candidate for non-invasive early detection, diagnosis, and surveillance of bladder cancer. The quantification and qualification of UcfDNA have demonstrated high sensitivity and specificity in the molecular characterization of bladder cancer. However, precise analysis of UcfDNA for clinical bladder cancer diagnosis remains challenging. This review summarizes the history of UcfDNA discovery, its biological properties, and the quantitative and qualitative evaluations of UcfDNA for its clinical significance and utility in bladder cancer patients, emphasizing the critical role of UcfDNA in bladder cancer diagnosis. Emerging bioactive technologies and materials currently offer promising tools for multiple UcfDNA analysis, aiming to achieve more precise and efficient capture of UcfDNA, thereby significantly enhancing diagnostic accuracy. This review also highlights breakthroughs in detection technologies and substrates with the potential to revolutionize bladder cancer diagnosis in clinic.

Abstract Neovascular age-related macular degeneration (nAMD) can result in blindness if left untreated, and patients often require repeated anti-vascular endothelial growth factor injections. Although, the treat-and-extend method is becoming popular to reduce vision loss attributed to recurrence, it may pose a risk of overtreatment. This study aimed to develop a deep learning model based on DenseNet201 to predict nAMD recurrence within 3 months after confirming dry-up 1 month following three loading injections in treatment-naïve patients. A dataset of 1076 spectral domain optical coherence tomography (OCT) images from 269 patients diagnosed with nAMD was used. The performance of the model was compared with that of 6 ophthalmologists, using 100 randomly selected samples. The DenseNet201-based model achieved 53.0% accuracy in predicting nAMD recurrence using a single pre-injection image and 60.2% accuracy after viewing all the images immediately after the 1st, 2nd, and 3rd injections. The model outperformed experienced ophthalmologists, with an average accuracy of 52.17% using a single pre-injection image and 53.3% after examining four images before and after three loading injections. In conclusion, the artificial intelligence model demonstrated a promising ability to predict nAMD recurrence using OCT images and outperformed experienced ophthalmologists. These findings suggest that deep learning models can assist in nAMD recurrence prediction, thus improving patient outcomes and optimizing treatment strategies.

Starch production from fresh sweet potatoes generates process wastewater called sweet potato cell liquid (SPCL), which is rich in sweet potato protein (SPP). Currently, the commonly used protein recovery methods, such as isoelectric point precipitation and ultrafiltration, were not suitable for SPP recovery due to the low protein content of SPCL and the high cost of recovery. The feasibility of recovering SPP by SPCL acidification via inoculation-assisted fermentation was investigated in this study. The results indicated that the pH of SPCL could be reduced to approximately 4.0 within 6 h of fermentation with inoculation, resulting in an SPP extraction yield of 55.45% and purity of 66.23 g protein/100 g. With the addition of heating treatment, the extraction yield of SPP increased to 76.97–95.34%, while it maintained the purity of 66.36–70.12 g protein/100 g. The composition analysis revealed that SPP products contained sugars (below 11.5 g/100 g) in addition to protein and trace amounts of lignin and phenolics. Functional properties analysis showed that the SPP recovered by inoculation-enhanced fermentation exhibited better emulsifying and foaming properties, and higher digestibility compared to the SPP precipitated using hydrochloric acid. The method of extracting SPP from SPCL by inoculation-enhanced fermentation, as developed in this study, was a straightforward and cost-effective process that fosters significant potential for industrial applications.

Abstract The nasal cavity harbors diverse microbiota that contributes to human health and respiratory diseases. However, whether and to what extent the host genome shapes the nasal microbiome remains largely unknown. Here, by dissecting the human genome and nasal metagenome data from 1401 healthy individuals, we demonstrated that the top three host genetic principal components strongly correlated with the nasal microbiota diversity and composition. The genetic association analyses identified 63 genome-wide significant loci affecting the nasal microbial taxa and functions, of which 2 loci reached study-wide significance (p

Abstract The Illumina HiSeq platform has been a commonly used option for bacterial genome sequencing. Now the BGI DNA nanoball (DNB) nanoarrays platform may provide an alternative platform for sequencing of bacterial genomes. To explore the impact of sequencing platforms on bacterial genome assembly, quality assessment, sequence alignment, functional annotation, mutation detection, and metagenome mapping, we compared genome assemblies based on sequencing of cultured bacterial species using the HiSeq 2000 and BGISEQ-500 platforms. In addition, simulated reads were used to evaluate the impact of insert size on genome assembly. Genome assemblies based on BGISEQ-500 sequencing exhibited higher completeness and fewer N bases in high GC genomes, whereas HiSeq 2000 assemblies exhibited higher N50. The majority of assembly assessment parameters, sequences of 16S rRNA genes and genomes, numbers of single nucleotide variants (SNV), and mapping to metagenome data did not differ significantly between platforms. More insertions were detected in HiSeq 2000 genome assemblies, whereas more deletions were detected in BGISEQ-500 genome assemblies. Insert size had no significant impact on genome assembly. Taken together, our results suggest that DNBSEQ platforms would be a valid substitute for HiSeq 2000 for bacterial genome sequencing.

Objective Circadian rhythm disruption (CRD) has been associated with inflammation and immune disorders, but its role in SLE progression is unclear. We aimed to investigate the impact of circadian rhythms on immune function and inflammation and their contribution to SLE progression to lupus nephritis (LN).Methods This study retrospectively analysed the clinical characteristics and transcriptional profiles of 373 samples using bioinformatics and machine-learning methods. A flare risk score (FRS) was established to predict overall disease progression for patients with lupus. Mendelian randomisation was used to analyse the causal relationship between CRD and SLE progression.Results Abnormalities in the circadian pathway were detected in patients with SLE, and lower enrichment levels suggested a disease state (normalised enrichment score=0.6714, p=0.0062). The disruption of circadian rhythms was found to be closely linked to lupus flares, with the FRS showing a strong ability to predict disease progression (area under the curve (AUC) of 5-year prediction: 0.76). The accuracy of disease prediction was improved by using a prognostic nomogram based on FRS (AUC=0.77). Additionally, Mendelian randomisation analysis revealed an inverse causal relationship between CRD and SLE (OR 0.6284 (95% CI 0.3630 to 1.0881), p=0.0485) and a positive causal relationship with glomerular disorders (OR 0.0337 (95% CI 1.634e-3 to 6.934e-1), p=0.0280).Conclusion Our study reveals that genetic characteristics arising from CRD can serve as biomarkers for predicting the exacerbation of SLE. This highlights the crucial impact of CRD on the progression of lupus.

Under the background of the continuous progress of China's agricultural reform, the development of characteristic agriculture is an important field of agricultural development in the country and even the world. Yunnan has unique advantages in geography, location, climate, and human resources, and has unique conditions for the development of agriculture with plateau characteristic. However, the sustainable development of agriculture with plateau characteristic is affected and restricted by many factors. How to promote the sustainable development of agriculture with plateau characteristic is an important research topic, and it is also the main purpose of this study. Therefore, through literature analysis and investigation, this study studies the advantages and disadvantages, development status, main problems, countermeasures and suggestions, macro development direction, and theoretical research methods of characteristic agriculture in the Yunnan plateau. This paper analyzes the advantages and disadvantages of the Decision-making Trial and Evaluation Laboratory (DEMATEL) and the Adversarial Interpretation Structure Modeling Method (AISM) and proposes to combine the two models to make up for each other and improve the accuracy of model analysis. On this basis, a set of identification and evaluation systems of factors affecting the sustainable development of agriculture with plateau characteristic is established, which can comprehensively and accurately identify and evaluate various influencing factors, and provide a scientific basis for the sustainable development of agriculture with plateau characteristic. Finally, combined with the relevant statistical data of Yunnan Province from 2009 to 2020 and many results calculated by the model, the factors affecting the sustainable development of agriculture with plateau characteristic were comprehensively analyzed. The results show that transportation, environment, and insurance support factors are the root factors that affect the sustainable development of agriculture with plateau characteristic, while the regional economy, scientific and technological support, and the development of agricultural enterprises are of high importance. Financial support, the level of agricultural mechanization, the quality of labor, and other factors can not be ignored. Finally, according to the results of the analysis, the corresponding policy recommendations are put forward to provide a reference for the sustainable development of plateau characteristic agriculture in Yunnan Province.

Parkinson's disease (PD) is the second most common neurodegenerative disorder with prominent dopamine (DA) neuron degeneration. PD affects millions of people worldwide, but currently available therapies are limited to temporary relief of symptoms. As an effort to discover disease-modifying therapeutics, we have conducted a screen of 1,403 bioactive small molecule compounds using an in vivo whole organism screening assay in transgenic larval zebrafish. The transgenic model expresses the bacterial enzyme nitroreductase (NTR) driven by the tyrosine hydroxylase (th) promotor. NTR converts the commonly used antibiotic pro-drug metronidazole (MTZ) to the toxic nitroso radical form to induce DA neuronal loss. 57 compounds were identified with a brain health score (BHS) that was significantly improved compared to the MTZ treatment alone after FDR adjustment (padj

Abstract Nanoparticles-based glues have recently been shown with substantial potential for hydrogel adhesion. Nevertheless, the transformative advance in hydrogel-based application places great challenges on the rapidity, robustness, and universality of achieving hydrogel adhesion, which are rarely accommodated by existing nanoparticles-based glues. Herein, we design a type of nanohesives based on the modulation of hydrogel mechanics and the surface chemical activation of nanoparticles. The nanohesives can form robust hydrogel adhesion in seconds, to the surface of arbitrary engineering solids and biological tissues without any surface pre-treatments. A representative application of hydrogel machine demonstrates the tough and compliant adhesion between dynamic tissues and sensors via nanohesives, guaranteeing accurate and stable blood flow monitoring in vivo. Combined with their biocompatibility and inherent antimicrobial properties, the nanohesives provide a promising strategy in the field of hydrogel based engineering.

The development of new urban areas in Beijing has alleviated overcrowding in old urban centers and has ample public spaces for recreational activities. However, these public spaces are not ideally designed and have not been as successful as expected. Few studies have investigated the ineffective use of these public spaces in terms of microclimatic and thermal comfort factors. Our study investigated microclimatic factors, the subjective assessment of thermal comfort, the intensity of human activities, and the spatial features of public spaces in conjunction with surrounding buildings in a mixed commercial and residential complex in the Fangshan District, Beijing. We used a mixed-methods approach comprising microclimate measurements, questionnaires (n = 150), spatiotemporal behavior mapping, and field measurements. Our results showed that the human perception of the microclimate is related to the exposure duration and other microclimatic factors. The perception of people who spend longer periods outdoors is often inconsistent with objectively measured thermal comfort values. Activity intensity (low, medium, and high) was also related to the duration of time spent outdoors. Microclimatic factors affect the number of people at different activity intensities and the trajectory of the activities. Different spatial features cause different microclimate formations and can directly influence the human subjective assessment of thermal comfort. This study uniquely links the microclimate to human perceptions, physical activities, and spatial features in service of redesigning public spaces. We developed a comprehensive methodology that expands the post-occupancy evaluation and proposes new urban public space designs that consider microclimates. This study also provides a new perspective for promoting physical activity by enhancing the thermal comfort of the environment to achieve physical and mental health goals.

Parkinson's disease (PD) is a common neurodegenerative disorder without effective disease-modifying therapeutics. Here, we establish a chemogenetic dopamine (DA) neuron ablation model in larval zebrafish with mitochondrial dysfunction and robustness suitable for high-content screening. We use this system to conduct an in vivo DA neuron imaging-based chemical screen and identify the Renin-Angiotensin-Aldosterone System (RAAS) inhibitors as significantly neuroprotective. Knockdown of the angiotensin receptor 1 (agtr1) in DA neurons reveals a cell-autonomous mechanism of neuroprotection. DA neuron-specific RNA-seq identifies mitochondrial pathway gene expression that is significantly restored by RAAS inhibitor treatment. The neuroprotective effect of RAAS inhibitors is further observed in a zebrafish Gaucher disease model and Drosophila pink1-deficient PD model. Finally, examination of clinical data reveals a significant effect of RAAS inhibitors in delaying PD progression. Our findings reveal the therapeutic potential and mechanisms of targeting the RAAS pathway for neuroprotection and demonstrate a salient approach that bridges basic science to translational medicine.

Pulmonary fibrosis (PF) is an interstitial lung disease with complex pathological mechanism, and there is currently a lack of therapeutics that can heal it completely. Using gene therapy with drugs provides promising therapeutic strategies for synergistically reversing PF. However, improving the intracellular accumulation and transfection efficiency of therapeutic nucleic acids is still a critical issue that urgently needs to be addressed. Herein, we developed lipid nanoparticles (PEDPs) with high transfection efficiency coloaded with pDNA of nuclear factor erythroid 2-related factor 2 (pNrf2) and pirfenidone (PFD) for PF therapy. PEDPs can penetrate biological barriers, accumulate at the target, and exert therapeutic effects, eventually alleviating the oxidative stress imbalance in type II alveolar epithelial cells (AECs II) and inhibiting myofibroblast overactivation through the synergistic effects of Nrf2 combined with PFD, thus reversing PF. In addition, we systematically engineered various liposomes (LNPs), demonstrated that reducing the polyethylene glycol (PEG) proportion could significantly improve the uptake and transfection efficiency of the LNPs, and proposed a possible mechanism for this influence. This study clearly reveals that controlling the composition ratio of PEG in PEDPs can efficiently deliver therapeutics into AECs II, improve pNrf2 transfection, and synergize with PFD in a prospective strategy to reverse PF.

Abstract Intermittent fasting (IF) is a promising paradigm for weight loss which has been shown to modulate the gut microbiota based on 16S rRNA gene amplicon sequencing. Here, 72 Chinese volunteers with a wide range of body mass index (BMI) participated in a three-week IF program during which an average loss of 3.67 kg body weight accompanied with improved clinical parameters was observed irrespective of initial anthropometric and gut microbiota status. Fecal samples were collected before and after the intervention and subjected to shotgun metagenomic sequencing. De novo assembly yielded 2934 metagenome-assembled genomes (MAGs). Profiling revealed significant enrichment of Parabacteroides distasonis and Bacteroides thetaiotaomicron after the intervention, with inverse correlations between their relative abundances and parameters related to obesity and atherosclerotic cardiovascular diseases (ASCVD). MAGs enriched after the intervention showed high richness and diversity of carbohydrate-active enzymes, with an increased relative abundances of genes related to succinate production and glutamate fermentation.

BackgroundAlthough previous research has made substantial progress in developing high-performance artificial intelligence (AI)–based computer-aided diagnosis (AI-CAD) systems in various medical domains, little attention has been paid to developing and evaluating AI-CAD system in ophthalmology, particularly for diagnosing retinal diseases using optical coherence tomography (OCT) images. ObjectiveThis diagnostic study aimed to determine the usefulness of a proposed AI-CAD system in assisting ophthalmologists with the diagnosis of central serous chorioretinopathy (CSC), which is known to be difficult to diagnose, using OCT images. MethodsFor the training and evaluation of the proposed deep learning model, 1693 OCT images were collected and annotated. The data set included 929 and 764 cases of acute and chronic CSC, respectively. In total, 66 ophthalmologists (2 groups: 36 retina and 30 nonretina specialists) participated in the observer performance test. To evaluate the deep learning algorithm used in the proposed AI-CAD system, the training, validation, and test sets were split in an 8:1:1 ratio. Further, 100 randomly sampled OCT images from the test set were used for the observer performance test, and the participants were instructed to select a CSC subtype for each of these images. Each image was provided under different conditions: (1) without AI assistance, (2) with AI assistance with a probability score, and (3) with AI assistance with a probability score and visual evidence heatmap. The sensitivity, specificity, and area under the receiver operating characteristic curve were used to measure the diagnostic performance of the model and ophthalmologists. ResultsThe proposed system achieved a high detection performance (99% of the area under the curve) for CSC, outperforming the 66 ophthalmologists who participated in the observer performance test. In both groups, ophthalmologists with the support of AI assistance with a probability score and visual evidence heatmap achieved the highest mean diagnostic performance compared with that of those subjected to other conditions (without AI assistance or with AI assistance with a probability score). Nonretina specialists achieved expert-level diagnostic performance with the support of the proposed AI-CAD system. ConclusionsOur proposed AI-CAD system improved the diagnosis of CSC by ophthalmologists, which may support decision-making regarding retinal disease detection and alleviate the workload of ophthalmologists.