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Abstract Puncture biopsy, especially those preserved by formalin fixed paraffin embedding (FFPE) samples, play an important role in various research purposes. Diverse single‐nucleus RNA sequencing (snRNA‐seq) techniques have been developed for FFPE samples, however, how to perform high‐throughput snRNA‐seq on small FFPE puncture samples is still a challenge. Here, the previously developed snRNA‐seq technique (snRandom‐seq) is optimized by implementing a pre‐indexing procedure for the minimal puncture FFPE samples. In analyzing 20 samples from various solid tumors, optimized snRandom‐seq still detected ≈17 000 genes and 12 000 long non‐coding RNAs (lncRNAs), achieving precise clustering based on tissue origin. A head‐to‐head comparison with 10× Genomics on fresh biopsy samples showed a similar gene detection rate, with significantly enhanced lncRNA detection, indicating that the optimized snRandom‐seq technique maintains its established gene detection advantages even when applied to small samples. Utilizing 7 puncture FFPE samples of liver metastases from 3 colorectal cancer patients pre‐ and post‐immunotherapy, the cellular developmental trajectories are reconstructed and revealed dynamic spatiotemporal heterogeneity during treatment, including insights into pseudoprogression of immunotherapy. Therefore, the optimized snRandom‐seq offers a solution for high‐throughput single‐cell RNA and non‐coding RNA analysis in minimal puncture FFPE sample.

Abstract Background Chinese medical schools have offered both professional and academic degrees for postgraduate students. However, there is limited information about the attitudes of professional-degree and academic-degree students. We aimed to examine the attitudes of full-time postgraduate students towards the curriculum, stratified by degree type. Methods A 29-item online questionnaire was distributed to postgraduate students in West China School of Medicine of Sichuan University in 2020. The questionnaire was designed to collect students’ demographic characteristics, attitudes towards curricular provision and content, and classroom organization. A comparison was made between groups based on degree type (academic degree versus professional degree). Results Overall, 645 out of 908 students at West China School of Medicine completed the questionnaire. Comparing with students pursuing academic degrees, professional-degree students were more interested if the curriculum included specialized knowledge and clinical skills, and expressed concerns over the excessive compulsory courses and inadequate optional courses (p

As a typical complex network system, the operating environment of rail transit network (RTN) is complex and demanding. This study aims to accurate assess the weaknesses and vulnerability of RTN, which is crucial for ensuring its smooth operation. Taking Chongqing Rail Transit (CRT) as an example, this study developed a network topology model using the spatial L method and analyzed the network structure characteristics, along with the importance of key nodes under different indicators, based on complex network theory. Additionally, this study analyzed the geographical spatial distribution characteristics of nodes based on the topography and urban spatial structure of Chongqing. Then, this study classified the nodes in the RTN according to basic topological indicators, namely degree, betweenness centrality, network efficiency, and passenger flow volume (PFV). The results indicated six cluster of nodes, reflecting the variability in node vulnerability concerning overall influence (providing alternative paths, reducing path length), regional aggregation capacity, and transportation capacity. Finally, this study proposed targeted management strategies for different clusters of nodes and their respective geographical locations, providing necessary references for rational planning, safety protection, and sustainable construction of RTN.

IntroductionCloud fitness is transforming indoor exercise for young people in China. Recent studies have explored the correlation between media use and health-promoting behavior by examining the motivation of individuals and the credibility of influencers. However, the role of media affordance has thus far been largely overlooked. Drawing on the theory of Stimulus-Organism-Response (SOR), the study investigated the indirect effect of visibility affordance on the intention to exercise with fitness influencers in the context of cloud fitness through psychological variables.MethodsThis paper, based on the online survey data (N = 456), analyses the effect of visibility affordance on the intention to fitness following with influencers. A moderated parallel mediation model was constructed to examine the relationship among related variables.ResultsThe paper draws the following conclusions: (1) Visibility affordance is positively related to the intention to exercise with fitness influencers. (2) Both the sense of social presence and immersion positively mediate the relationship between visibility affordance and the intention to exercise with fitness influencers. (3) The perceived popularity of the influencer positively moderates the relationship between social presence and the intention to exercise with fitness influencers and moderates the mediating role of social presence.DiscussionConsequently, this study enhances the existing body of knowledge in exercise behavior and health communication literature, and provides practical implications for short video platform, influencers and individuals in promoting healthier behaviors.

Abstract Formalin-fixed paraffin-embedded (FFPE) tissues constitute a vast and valuable patient material bank for clinical history and follow-up data. It is still challenging to achieve single cell/nucleus RNA (sc/snRNA) profile in FFPE tissues. Here, we develop a droplet-based snRNA sequencing technology (snRandom-seq) for FFPE tissues by capturing full-length total RNAs with random primers. snRandom-seq shows a minor doublet rate (0.3%), a much higher RNA coverage, and detects more non-coding RNAs and nascent RNAs, compared with state-of-art high-throughput scRNA-seq technologies. snRandom-seq detects a median of >3000 genes per nucleus and identifies 25 typical cell types. Moreover, we apply snRandom-seq on a clinical FFPE human liver cancer specimen and reveal an interesting subpopulation of nuclei with high proliferative activity. Our method provides a powerful snRNA-seq platform for clinical FFPE specimens and promises enormous applications in biomedical research.

ObjectiveTo determine the association between the burden of cerebral small vessel disease (CSVD) due to hypertensive angiopathy (HA) and cerebral amyloid angiopathy (CAA) on MRI in patients with primary intracerebral hemorrhage (ICH).MethodsPatients with primary ICH admitted to our center from March 2012 to November 2021 were consecutively enrolled. We used multivariate binary and ordinal regression analyses to assess the association between HA-CSVD burden and CAA-CSVD burden. Lobar cerebral microbleeds (CMBs) were categorized into three level of severity: 0–1, 2–4, and ≥ 5 lobar CMBs. A high CAA-CSVD score was defined as a CAA-CSVD score of ≥3.ResultsOverall, 222 participants (mean age 59.88 ± 13.56) were included into analysis. Age and ICH etiology differed among different lobar CMB severity and between the presence and absence of high CAA-CSVD score (all p

The construction of tourist villages is an important implementation path for promoting the new urbanization strategy in China. The optimization of their spatial pattern and functional adjustment is a key way to achieve high-quality urban development. The purpose of this study is to determine the influencing factors of public space vitality in tourist villages from the perspective of human behavior activities and to provide design support strategies for enhancing the vitality of public spaces in tourist villages. Using Mochou Village as an example, physical and behavioral network models were used to conduct a quantitative study of the vitality characteristics, and Quantitative Analysis of Precedence (QAP) regression was used to investigate the influence factors. The results demonstrate that spatial characteristics, such as “small block size, high street density”, and grid-like street structure and squares, as well as factors such as store concentration, sight lines, street length, spatial openness, and street width, significantly impact the vitality of public spaces in tourist villages. The analysis of the characteristics of the vitality of public space networks in tourist villages and the discussion of the influencing factors of public space vitality in this study can provide guidance for evaluating the vitality of public spaces and designing public spaces with high vitality in tourist villages.

With the deceleration of urban expansion, the adaptive reuse of industrial heritage buildings has emerged as a novel area of research. In previous times, the majority of approaches to adapting industrial heritage buildings relied on experiential knowledge, which lacked the ability to objectively assess the relationship between spaces and engage in rational planning. However, the social network analysis method offers an objective and comprehensive means of perceiving the spatial structure and analyzing its issues from a detached perspective. This study presents a proposal for addressing three spatial challenges encountered during the conversion of industrial heritage buildings into public buildings. It also suggests spatial optimization strategies to overcome these challenges. The Sanlinqiao Thermal Bottle Factory is selected as the research subject, and a spatial network structure model is constructed to analyze the existing issues using the social network analysis method. The proposed spatial optimization strategies are then applied, and the optimized space is evaluated through a re-analysis of the spatial layout. The spatial utilization rate has been significantly improved, leading to an effective enhancement of the spatial vitality of the site. This study presents a spatial strategy aimed at converting industrial heritage buildings into public buildings, thereby offering valuable insights for similar projects involving the transformation of industrial heritage sites.

Abstract Objective Recombinant immunotoxins (RITs) are antibody-toxin fusion proteins that can selectively eliminate populations of cells expressing specific surface receptors. They are in evaluation as therapeutic agents for cancer. RITs based on Pseudomonas exotoxin A (PE) are in use clinically for the treatment of hairy cell leukemia, and under trial for the treatment of other cancers. In an effort to improve the efficacy of PE-based RITs, we evaluated the potential of combination therapy with several common antibiotics (tetracycline, chloramphenicol, streptomycin, linezolid, fusidic acid, and kanamycin) on human cell lines HEK293, OVCAR8, and CA46. Antibiotics were selected based on their potential to inhibit mitochondrial protein synthesis and disrupt energy metabolism in cancer cells. Results Tetracycline, chloramphenicol, linezolid, and fusidic acid alone killed cultured human cells at high concentrations. At high but nontoxic concentrations of each antibiotic, only chloramphenicol treatment of the Burkitt’s lymphoma cell line CA46 showed enhanced cytotoxicity when paired with an anti-transferrin receptor/PE RIT. This result, however, could not be replicated in additional Burkitt’s lymphoma cell lines Ramos and Raji. Although the six antibiotics we tested are not promising candidates for RIT combination therapy, we suggest that fusidic acid could be considered independently as a potential cancer therapeutic.

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Similar to light detection and ranging (lidar), profile radar can detect forest vertical structure directly. Recently, the first Ku-band profile radar system designed for forest applications, called Tomoradar, has been developed and evaluated in boreal forest. However, the physical relationships between the waveform and forest structure parameters such as height, leaf area index (LAI), and aboveground biomass are still unclear, which limits later forestry applications. Therefore, it is necessary to develop a theoretical model to simulate the relationship and interpret the mechanism behind. In this study, we extend the Radiosity Applicable to Porous IndiviDual objects (RAPID2) model to simulate the profile radar waveform of forest stands. The basic assumption is that the scattering functions of major components within forest canopy are similar between profile radar and the side-looking radar implemented in RAPID2, except several modifications. These modifications of RAPID2 mainly include: (a) changing the observation angle from side-looking to nadir-looking; (b) enhancing the ground specular scattering in normal direction using Fresnel coefficient; (c) increasing the timing resolution and recording waveform. The simulated waveforms were evaluated using two plots of Tomoradar waveforms at co- and cross- polarizations, which are collected in thin and dense forest stands respectively. There is a good agreement (R2 ≥ 0.80) between the model results and experimental waveforms in HH and HV polarization modes and two forest scenes. After validation, the extended RAPID2 model was used to explore the sensitivity of the stem density, single tree LAI, crown shape, and twig density on the penetration depth in the Ku-band. Results indicate that the backscattering of the profile radar penetrates deeper than previous studies of synthetic aperture radar (SAR), and the penetration depth tends to be several meters in Ku-band. With the increasing of the needle and twig density in the microwave propagation path, the penetration depth decreases gradually. It is worth noting that variation of stem density seems to have the least effect on the penetration depth, when there is no overlapping between the single tree crowns.

The commonly believed mechanism of colistin against Gram-negative bacteria is to cause cell membrane lysis, whereas the mechanism of colistin against Gram-positive bacteria is extremely fragmented. In this study, we found that colistin treatment on Bacillus subtilis WB800, Paenibacillus polymyxa C12 and Paenibacillus polymyxa ATCC842 enhances not only the activities of α-ketoglutaric dehydrogenase and malate dehydrogenase in tricarboxylic acid (TCA) cycle, but also the relative expression levels of their encoding genes. Additionally, the oxaloacetate concentration also increases. Interestingly, the analysis of the relative expression of genes specific for respiratory chain showed that colistin treatment stimulates the respiratory chain in Gram-positive bacteria. Accordingly, the NAD+/NADH ratio increases and the oxidative level is then boosted up. As a result, the intensive oxidative damages are induced in Gram-positive bacteria and cells are killed. Notably, both rotenone and oligomycin, respectively, inhibiting NADH dehydrogenase and phosphorylation on respiratory chain can downgrade oxidative stress formation, thus alleviating the colistin-induced killing of Gram-positive cells. Besides, thiourea-based scavenging for reactive oxygen species also rescues the colistin-subjected cells. These data collectively demonstrate that colistin stimulates both TCA cycle and respiratory chain in Gram-positive bacteria, leading to the enhancement of NADH metabolism and resulting in the generation of oxidative damages in Gram-positive cells. Our studies provide a better understanding of antibacterial mechanism of colistin against Gram-positive bacteria, which is important for knowledge on bacterial resistance to colistin happening via the inhibition of respiratory chain and manipulation of its production.