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Abstract Corticosteroids have always been recommended for severe cases of COVID-19. However, the efficacy of treatment with corticosteroids for COVID-19 during the SARS-CoV-2 omicron outbreak in China has not been reported. Clinical data from 406 patients hospitalized for severe/critical COVID-19 from December 2022 to January 2023 at six hospitals in Chongqing were retrospectively analyzed. The primary outcome was all-cause mortality at 28 days in the groups with and without corticosteroids treatment after propensity score matching (PSM). Secondary outcomes were to compare in-hospital mortality and length of survival time with corticosteroids and those without corticosteroids. This study included 406 patients with severe or critical COVID-19, divided into the corticosteroids group (231, 56.9%) and non-corticosteroids group (175, 43.1%). After PSM, the use of corticosteroids did not reduce all-cause mortality at 28 days (42.5% vs. 39.1%). Univariate analysis showed that corticosteroids were not associated with improved all-cause mortality at 28 days [hazard ratio (HR), 1.019; 95% confidence interval (CI), 0.639–1.623; p = 0.938]. Multivariate analysis showed similar results (HR, 1.047; 95% CI, 0.633–1.732; p = 0.858). Among non-survivors, the survival time was significantly larger in those who received corticosteroids compared with the non-corticosteroid users [median 13 (IQR 6.5–15.5) vs. 6 (4-11.25), p = 0.007]. The use of systemic corticosteroids in severe/critical COVID-19 may provide certain potential survival benefits but does not improve prognosis.

Humans perceive their surrounding environments largely through their experiences of sight and hearing. The perceived environmental information then brings on neurophysiological changes, so as to influence human emotions. These mutually influenced relations have been widely utilized by many environmental psychologists to explore potential avenues for improving human emotions through design interventions. However, to date, no efficient and accurate way has been established to describe these relationships. Inspired by Russell’s model of emotion, this study aims to develop an efficient process that uses coordinate mapping and can intuitively describe the impact of visual-aural perceptive attributes on human emotions. Taking typical urban green spaces (UGSs) in Chengdu as examples, this study first measured the visual and aural characteristics of study sites perceived by people and their emotional responses. The study then established the use of emotional status on a coordinate axis, allowing each visual-aural attribute corresponding to each emotional response to be projected onto the coordinates. Results suggested that the dataset composed of 279 evaluations could be classified into three distinct types of visual-aural settings and the distribution of emotions is evidently varied in different settings. It was found that aesthetic and order of visual aspects as well as eventful and harmonious soundscape in environments are more likely to make people feel pleasure, while openness and layering of the visual landscape can easily arouse people’s positive status. The research outcome broadens the practical path of soundscape research, centring on human emotions, experiences and feelings, such as the pleasantness and arousal raised in Russell’s theory of emotion. The study also makes an empirical contribution to the design of UGSs based on multi-sensory perception and serves the purpose of improving people’s environmental experiences.

Objective: To study the effect and action mechanism of compound collagen peptides powder on chronic skin damage resulting from ultraviolet irradiation in mice. Methods: Female ICR mice were randomly divided into the following groups according to their weights: Normal, model, compound collagen peptides powder, fish collagen peptide. Mice in the model and treatment groups were irradiated on back skin using UV phototherapy apparatus to induce chronic skin damage. During the experiment, the skin appearance of mice was scored each week and photos were taken every 3 weeks. The skin water content was determined by drying method after 9 weeks. The histopathological changes of mice skin were observed using Hematoxylin-Eosin (HE) staining. The total antioxidant capacity (T-AOC) in skin was detected using fluorescene recovery after photobleaching (FRAP). The levels of type I collagen (Col I), elastin (ELN), hyaluronic acid (HA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA) and advanced glycation end products (AGEs) in the skin were examined using ELISAs. RT-PCR and Western blot analyses were performed to determine the mRNA and protein expression of transforming growth factor β1 (TGF-β1), transforming growth factor β receptor 2 (TGF-βR2), Smad2, Smad3 and Smad7. Results: Compared to the model group, mice in the compound collagen peptides powder group had less wrinkles, no epidermal damage and the skin scores were significantly decreased (P

Abstract Background The efficacy of immune checkpoint inhibitors (ICIs) in pleural mesothelioma has recently been established. The response to ICIs can be predicted by quantitative analysis of cells and their spatial distribution in the tumor microenvironment (TME). However, the detailed composition of the TME in pleural mesothelioma has not been reported. We evaluated the association between the TME and response to ICIs in this cancer. Methods A retrospective analysis of 22 pleural mesothelioma patients treated with nivolumab in different centers was performed using surgical specimens. Four patients had a partial response to nivolumab (response group) and 18 patients had stable or progressive disease (nonresponse group). The number of CD4, CD8, FoxP3, CK, and PD‐L1 positive cells, cell density, and cell‐to‐cell distance were analyzed by multiplex immunofluorescence. Results PD‐L1 expression did not differ significantly between the response and nonresponse groups. The density of total T cells and of CD8+ T cells was significantly higher in the response than in the nonresponse group. CD8+ T cells were more clustered and located closer to tumor cells, whereas regulatory T cells were located further from tumor cells in the response than in the nonresponse group. Conclusions High density and spatial proximity of CD8+ T cells to tumor cells were associated with better response to nivolumab, whereas the proximity of regulatory T cells to tumor cells was associated with worse response, suggesting that the distinct landscape of the TME could be a potential predictor of ICI efficacy in pleural mesothelioma.

Inflammatory bowel diseases (IBD) are chronic intestinal disorders that result from an inappropriate inflammatory response to the microbiota in genetically susceptible individuals, often triggered by environmental stressors. Part of this response is the persistent inflammation and tissue injury associated with deficiency or excess of reactive oxygen species (ROS). The NADPH oxidase NOX1 is highly expressed in the intestinal epithelium, and inactivating NOX1 missense mutations are considered a risk factor for developing very early onset IBD. Albeit NOX1 has been linked to wound healing and host defence, many questions remain about its role in intestinal homeostasis and acute inflammatory conditions. Here, we used in vivo imaging in combination with inhibitor studies and germ-free conditions to conclusively identify NOX1 as essential superoxide generator for microbiota-dependent peroxynitrite production in homeostasis and during early endotoxemia. NOX1 loss-of-function variants cannot support peroxynitrite production, suggesting that the gut barrier is persistently weakened in these patients. One of the loss-of-function NOX1 variants, NOX1 p. Asn122His, features replacement of an asparagine residue located in a highly conserved HxxxHxxN motif. Modelling the NOX1-p22phox complex revealed near the distal heme an internal pocket restricted by His119 and Asn122 that is part of the oxygen reduction site. Functional studies in several human NADPH oxidases show that substitution of asparagine with amino acids with larger side chains is not tolerated, while smaller side chains can support catalytic activity. Thus, we identified a previously unrecognized structural feature required for the electron transfer mechanism in human NADPH oxidases.

IntroductionNature-based solutions (NBS) have been used to address a wide range of urban environmental challenges, an important aspect of which is to improve human health and well-being. However, most relevant studies focus either on what positive influences nature may have or on identifying what natural factors can have these benefits. Few have investigated the sensory composition of nature and the effects of nature in different sensory aspects on human health. Setting out from the multi-sensory perspective, this study aims to explore human behavior and emotional response from visual and aural contact with urban nature.MethodsTaking Jiangjia Art Garden in Chengdu as an example, natural attributes such as its visual (landscape) and aural (sound source) characteristics as well as people’s activities (behavioral responses) were measured by on-site mapping analysis. This was done while a questionnaire-based survey was conducted to investigate people’s emotional responses regarding their overall satisfaction, pleasantness, calm, and agreeableness.ResultsThe results indicated that nature-dominated visual landscapes such as grassland, waterscapes, and woodlands, as well as natural sounds such as bird sounds, chirp sounds, and wind sounds were found to be positively correlated to the vitality of activities and people’s emotional status. Regarding behavioral responses, it was shown that grasslands and woodlands are more likely to be attractive places for recreation, and the vitality measured became extremely high when these two were paired with lakes. As for the emotional responses, people’s perceived overall satisfaction, calm, and agreeableness were equally reflected in their behavioral patterns, suggesting a strong relationship with natural factors.DiscussionThe research findings were visually presented in behavior and emotional maps to provide direct cues of informing the future design of high-quality urban green spaces and promoting the application of aural-visual experience in the design of urban nature areas.

Abstract Background Bladder cancer (BLCA) is one of the most diagnosed cancers in humans worldwide. Recently, immunotherapy has become a main treatment option for BC. However, most BLCA patients do not respond to immune checkpoint inhibitors or relapse after immunotherapy. Therefore, it is very important to identify novel biomarkers for the prediction of immunotherapy response in B patients. Methods Pancancer single‐cell RNA sequencing (scRNA‐seq) data were used to identify the clusters of CD4+ T cells in the tumour microenvironment (TME). The clinical significance of key CD4+ T‐cell clusters was evaluated based on the survival data of two independent immunotherapy bladder cancer (BLCA) cohorts. We also investigated the function of key clusters of CD4+ T cell in the TME of BC cells in vitro. Results This study identified two novel exhausted CD4+ T‐cell subpopulations with the expression of PD1hi CD200hi or PD1hi CD200low in BC patients. Moreover, BLCA patients with a high level of PD1hi CD200hi CD4+ exhausted T cell showed immunotherapy resistance. Cell function analysis demonstrated that PD1hi CD200hi CD4+ exhausted T cell can promote epithelial–mesenchymal transition (EMT) and angiogenesis in BLCA cells. In addition, PD1hi CD200hi CD4+ exhausted T cells were shown to communicate with malignant BLCA cells through the GAS6–AXL axis. Finally, we also found that GAS6 expression is upregulated in B cells by METTL3‐mediated m6A modification. Conclusions PD1hi CD200hi CD4+ exhausted T cell may serve as a novel biomarker for poor prognosis and immunotherapy resistance in B. Targeted inhibitors of PD1hi CD200hi CD4+ exhausted T cells may help improve the efficacy of immunotherapy.

Environmental justice research largely focuses on the allocation of public resources in terms of quantified distribution and accessibility. This study suggests that the quality of landscape equity, an important urban resource, should be evaluated as it typically appears as a combination of elements. This brings another perspective to the attention of landscape equity in addition to the provision equity: the equity in the quality and level of provision. From this perspective, this study explores the equitable role of streetscape qualities in promoting human physical, mental, and social health. Using street view images, questionnaires, artificial intelligence-based image analysis, geographic information system-based cluster analysis, and correlational analysis, the spatial distribution of health promotion streetscapes and health-influential streetscape elements were presented and compared within the scope of the Shanghai Outer Ring Road. The results disclosed an uneven distribution of streetscapes that can promote human health within research sites. Streets with poor health ratings are concentrated in the Huangpu, Hongkou, and Yangpu districts, primarily in the western part of Shanghai around Shanghai Railway Station, People’s Square, and Yuyuan Garden, where the old city centre is located. Compared with the distribution of health-influential elements, less healthy streets are more likely to be accompanied by low visibility of ‘vegetation’ and a high proportion of ‘buildings’. Streetscape design implications were then discussed in terms of providing people with equal health opportunities. Research outcomes inspired an essential quality perspective in health equity research, and it can be especially helpful when the provision and accessibility can hardly be moderated in high-density cities.

Background and objectiveInsulin-like growth factor-1 (IGF-1) regulates cardiomyocyte survival, hypertrophy, and ageing. We aimed to investigate the potential correlation between IGF-1 and interventricular septal (IVS) thickening.MethodsMedical record data were obtained from patients hospitalized between May 1, 2012 and April 30, 2022. All patients underwent echocardiography and had laboratory data on plasma IGF-1. We analyzed the relationship between IGF-1 levels and IVS thickening based on logistic regression models.ResultsPropensity score matching at 1:4 ratio was performed for 180 patients with IVS thickening and 1,964 patients without IVS thickening. Finally, 180 (case group) and 623 (control group) patients were enrolled. Of the total 803 patients, the mean age was 59 years, and 59.7% were male. In multivariate-adjusted models that adjusted for propensity scores, the risk of IVS thickening increased with increasing IGF-1 levels; specifically, the risk of IVS thickening increased per 1 ng/mL [odds ratio (OR) 1.003; 95% confidence interval (CI): 1.002–1.004; P < 0.001], per 5 ng/mL (OR, 1.016; 95% CI, 1.010–1.022; P < 0.001), and per 10 ng/mL(OR, 1.032; 95% CI, 1.019–1.045; P < 0.001) increase in IGF-1 levels. When the IGF-1 levels were expressed as a categorical variable, the increased levels of IGF-1 led to an increased risk of IVS thickening; specifically, the OR of IVS thickening for T3 >152.00 ng/mL was 2.020 (95% CI: 1.310–3.115, P < 0.01) compared with T1 164.00 ng/mL, 45–60 years when IGF-1 value > 140.34 ng/mL and ≥ 60 years when IGF-1 value >108.20 ng/mL. In female patients aged 45–60 years, the risk of IVS thickening increased when the IGF-1 levels were >207.45 ng/mL. However, IGF-1 was not significantly correlated with IVS thickening in female patients aged 18–45 and ≥60 years. Sensitivity analysis by excluding those with acromegaly did not change the relationship between IGF-1 and the risk of IVS thickening.ConclusionThe plasma IGF-1 levels were related to the risk of IVS thickening irrespective of blood pressure.

BackgroundThe covered self-expandable metallic stents (SEMS) have been used to manage benign tracheobronchial stenosis, especially the complex post-tuberculosis (TB) tracheobronchial stenosis (PTTS) with cartilage destruction or malacia. This procedure could lead to stent-related tracheoesophageal fistula (TEF).Case presentationA 21-year-old woman, who had one covered Y-shaped SEMS inserted to manage complex PTTS 2 years ago, presented with dyspnea and frequent coughing on drinking water. The bronchoscopy confirmed extensive granulation tissue hyperplasia and a TEF on the upper edge of the covered SEMS. The covered SEMS was removed in three steps, and another fully covered Y-shape SEMS (Microtech Co., Ltd., Nanjing, China) was inserted to restore patency in the tracheobronchial tree and occlude the TEF orifice. Recombinant bovine basic fibroblast growth factor (rbFGF) (6,000 IU/time) was sprayed into and around the fistula through the V-System single-use cannula via the flexible bronchoscope every other week. The patient showed sustained clinical and radiographic improvement, and the TEF healed.ConclusionWe presented a three-step bronchoscopic approach to managing a stent-related TEF in a patient with complex PTTS. Subsequently, regular bronchoscopic debridement of granulation tissue developing on the upper edge of SEMS is necessary to maintain the stent patency and reduce the risk of recurrent stent-related TEF. A fully covered SEMS associated with the local administration of rbFGF seems to offer an alternative simplified one-stage procedure for the temporary management of TEF combined with complex PTTS in non-surgical candidates.

Success in delivering dynamic urban coastal zones is considered essential, as it brings enormous opportunities to the social, economic, ecological, and cultural development of the cities in addition to benefitting the coastal zones. However, the environmental drivers contributing to urban coastal zone vitality remain uncertain due to unclarified spatial boundaries and the influences of diverse characteristics from surrounding contexts. This study aims at exploring environmental drivers that can vitalize urban coastal zones and can inform an effective way to instruct design procedures. It sets out from clarifying the spatial boundaries of urban coastal zones and emphasizing the mutual connections among its spatial components. A data-driven multi-method approach is used to analyze spatial forms, traffic organizations, land uses, landscape characteristics, and coastal functions of the eight typical coastal cases selected in different countries. Results suggested that six typical coastal zone types can be classified based on landscape characteristics and coastal functions, while the other vitality-related aspects, spatial forms, traffic organizations, and land uses are analyzed to imply design requirements for each type. It is found that requirements on vitality-related aspects of the six types evidently vary with the coastal functions, but there are similarities among the types with similar landscape characteristics.

Abstract Cancer-secreted exosomes are critical mediators of cancer-host crosstalk. In the present study, we showed the delivery of miR-21-5p from colorectal cancer (CRC) cells to endothelial cells via exosomes increased the amount of miR-21-5p in recipient cells. MiR-21-5p suppressed Krev interaction trapped protein 1 (KRIT1) in recipient HUVECs and subsequently activated β-catenin signaling pathway and increased their downstream targets VEGFa and Ccnd1, which consequently promoted angiogenesis and vascular permeability in CRC. A strong inverse correlation between miR-21-5p and KRIT1 expression levels was observed in CRC-adjacent vessels. Furthermore, miR-21-5p expression in circulating exosomes was markedly higher in CRC patients than in healthy donors. Thus, our data suggest that exosomal miR-21-5p is involved in angiogenesis and vascular permeability in CRC and may be used as a potential new therapeutic target.

BackgroundSelf-expanding metallic stent (SEMS) is a palliative therapy for patients with malignant central airway obstruction (CAO) or tracheoesophageal fistula (TEF). Despite this, many patients experience death shortly after SEMS placement.AimsWe aimed to investigate the effect of SEMS on the palliative treatment between malignant CAO and malignant TEF patients and investigate the associated prognostic factors of the 3-month survival.MethodsWe performed a single-center, retrospective study of malignant CAO or TEF patients receiving SEMS placement. Clinical data were collected using the standardized data abstraction forms. Data were analyzed using SPSS 22.0. A two-sided P-value

Environmental perception studies have long been constrained by research scales due to the difficulties in obtaining users’ perceptive data and constructing their relation to environmental attributes. With the help of big data from street view images, this study compares the visual comfort of streets across four Chinese megacities with evidently distinct geographical characteristics. A multi-method approach involving traditional comfort measurements, image analysis based on deep learning algorithms and spatial mapping using geographic information systems was used to investigate the visual components of urban streets at the city scale and their influential mechanisms. In general, the four cities ranked by visual comfort were Beijing first, then Shenzhen, Shanghai and Guangzhou. The results also suggested that the spatial distribution of the four cities’ street visual comfort is obviously different. In Shanghai and Beijing, streets with a higher comfort level are mostly concentrated within the central city, while the highly comfort streets are mostly distributed along the coast and rivers in Shenzhen and Guangzhou. Thus, it is reasonable to speculate that the streets’ visual comfort relates significantly to their urban planning and construction process. Moreover, seven indicators have been identified as influential to street comfort, among which ‘vegetation’, ‘terrain’ and ‘rider’ are positive indicators, while ‘architecture’, ‘pedestrians’, ‘motorcycles’ and ‘bicycles’ have negative influences. Comparing street comfort indicators of the four case study cities, it was observed that ‘vegetation’ and ‘terrain’ have the most consistent positive influences across cities, while the high visibility of ‘building’ on streets is most likely to lead to a low level of perceived comfort. The research outcomes provide applicable cues for large-scale street evaluation research and illustrate an efficient street design approach that can both respond to local characteristics and human perceptive needs.

BackgroundColorectal cancer (CRC) is a common malignant solid tumor with an extremely low survival rate after relapse. Previous investigations have shown that autophagy possesses a crucial function in tumors. However, there is no consensus on the value of autophagy-associated genes in predicting the prognosis of CRC patients. This work screens autophagy-related markers and signaling pathways that may participate in the development of CRC, and establishes a prognostic model of CRC based on autophagy-associated genes.MethodsGene transcripts from the TCGA database and autophagy-associated gene data from the GeneCards database were used to obtain expression levels of autophagy-associated genes, followed by Wilcox tests to screen for autophagy-related differentially expressed genes. Then, 11 key autophagy-associated genes were identified through univariate and multivariate Cox proportional hazard regression analysis and used to establish prognostic models. Additionally, immunohistochemical and CRC cell line data were used to evaluate the results of our three autophagy-associated genes EPHB2, NOL3, and SNAI1 in TCGA. Based on the multivariate Cox analysis, risk scores were calculated and used to classify samples into high-risk and low-risk groups. Kaplan-Meier survival analysis, risk profiling, and independent prognosis analysis were carried out. Receiver operating characteristic analysis was performed to estimate the specificity and sensitivity of the prognostic model. Finally, GSEA, GO, and KEGG analysis were performed to identify the relevant signaling pathways.ResultsA total of 301 autophagy-related genes were differentially expressed in CRC. The areas under the 1-year, 3-year, and 5-year receiver operating characteristic curves of the autophagy-based prognostic model for CRC were 0.764, 0.751, and 0.729, respectively. GSEA analysis of the model showed significant enrichment in several tumor-relevant pathways and cellular protective biological processes. The expression of EPHB2, IL-13, MAP2, RPN2, and TRAF5 was correlated with microsatellite instability (MSI), while the expression of IL-13, RPN2, and TRAF5 was related to tumor mutation burden (TMB). GO analysis showed that the 11 target autophagy genes were chiefly enriched in mRNA processing, RNA splicing, and regulation of the mRNA metabolic process. KEGG analysis showed enrichment mainly in spliceosomes. We constructed a prognostic risk assessment model based on 11 autophagy-related genes in CRC.ConclusionA prognostic risk assessment model based on 11 autophagy-associated genes was constructed in CRC. The new model suggests directions and ideas for evaluating prognosis and provides guidance to choose better treatment strategies for CRC.

Colorectal cancer (CRC) is the primary cause of cancer-related death worldwide; however, specific and sensitive tools for the early diagnosis and targeted therapy of CRC are currently lacking. High-throughput sequencing technology revealed that gene expression of long-chain non-coding RNAs (lncRNAs) in a number of cancers directly or indirectly interferes with various biological processes. Emerging evidence suggests that lncRNAs regulate target genes and play an important role in the biological processes of malignancies, including CRC. Many carcinostatic/oncogenic lncRNAs have been identified as biomarkers for metastasis and prognosis in CRC; hence, they serve as therapeutic tools. In this article, we systematically review the literature on the disordered lncRNAs in CRC from four aspects: DNA transcription, RNA level regulation, post-translational level, and the translation of lncRNAs into polypeptides. Subsequently, we analyze the mechanism through which lncRNAs participate in the biological process of CRC. Finally, we discuss the application and prospects of these lncRNAs in CRC.

Ionic liquids (ILs) are a class of pure ions with melting points lower than 100 °C. They are getting more and more attention because of their high thermal stability, high ionic conductivity and dielectric properties. The unique dielectric properties aroused by the ion motion of ILs makes ILs-contained inorganics or organics responsive to electric field and have great application potential in smart electrorheological (ER) fluids which can be used as the electro-mechanical interface in engineering devices. In this review, we summarized the recent work of various kinds of ILs-contained inorganic ionogels and poly(ionic liquid)s (PILs) as ER materials including their synthesis methods, ER responses and dielectric analysis. The aim of this work is to highlight the advantage of ILs in the synthesis of dielectric materials and their effects in improving ER responses of the materials in a wide temperature range. It is expected to provide valuable suggestions for the development of ILs-contained inorganics and PILs as electric field responsive materials.

TNFα is one of the initial and important mediators to activate downstream signaling pathways by binding to trimerized TNFα receptors (TNFR), and thus is an ideal drug target for cancer therapy. Taking advantage of intrinsic homotimerization of the globular domain of adiponectin (gAD), we have developed a novel TNFα antagonist, the trimerized fusion protein named sTNFRII-gAD. However, our previously-used CHO expression system yielded less than 10 mg/L of sTNFRII-gAD. To produce large quantities of sTNFRII-gAD efficiently, we used a modified CHO-S cell expression system, which is based on a pMH3 vector with non-coding GC-rich DNA fragments for high-level gene expression. We obtained stable clones that produced 75 mg/L of sTNFRII-gAD in the 96-well plate, adapted the clones to 40 ml suspension serum-free batch culture, then optimized the culturing conditions to scale up the fed-batch culture in a 3 L shake-flask and finally in a 5 L AP30 bioreactor. We achieved a final yield of 52 mg/L of sTNFRII-gAD. The trimerized sTNFRII-gAD exhibited the higher affinity to TNFα with a dissociation constant (Kd) of 5.63 nM than the dimerized sTNFRII-Fc with a Kd of 13.4 nM, and further displayed the higher TNFα-neutralizing activity than sTNFRII-Fc (p