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Abstract Background Renal cell carcinoma (RCC) is a type of cancer that can develop at any point in adulthood, spanning the range of age-related changes that occur in the body. However, the specific molecular mechanisms underlying the connections between age and genetic mutations in RCC have not been extensively investigated. Methods Clinical and genetic data from patients diagnosed with RCC were collected from two prominent medical centers in China as well as the TCGA dataset. The patients were categorized into two groups based on their prognosticated age: young adults (YAs) and older adults (OAs). Univariate and multivariate analysis were employed to evaluate the relationships between age and genetic mutations. Furthermore, a mediation analysis was conducted to assess the association between age and overall survival, with genetic disparities serving as a mediator. Results Our analysis revealed significant differences in clinical presentation between YAs and OAs with RCC, including histopathological types, histopathological tumor stage, and sarcomatoid differentiation. YAs were found to have lower mutation burden and significantly mutated genes (SMGs) of RCC. However, we did not observe any significant differences between the two groups in terms of 10 canonical oncogenic signaling pathways-related genes mutation, telomerase-related genes (TRGs) mutation, copy number changes, and genetic mutations associated with clinically actionable targeted drugs. Importantly, we demonstrate superior survival outcomes in YAs, and we confirmed the mediating effect of genetic disparities on these survival outcome differences between YAs and OAs. Conclusion Our findings reveal previously unrecognized associations between age and the molecular underpinnings of RCC. These associations may serve as valuable insights to guide precision diagnostics and treatments for RCC.

Abstract An object detection framework using thermal infrared (TIR) cameras is proposed to meet the needs of an advanced driver assistance system (ADAS) operating at night‐time and in low‐visibility conditions. The proposed detection framework, referred to as TIR‐YOLO‐ADAS, is an improvement of YOLOX for TIR object detection in ADAS. First, to address the disadvantages of TIR objects, the part of the attention mechanism is designed to enhance the discriminative ability of feature maps in the spatial and channel dimensions. Second, a focal loss function is used as the confidence loss function to enable the framework to focus on detection tasks of difficult, misclassified targets in the process of network training. The results of the ablation experiment on the Forward‐looking infrared (FLIR) thermal ADAS dataset indicate that the proposed framework significantly improves the performance of TIR object detection. Comparative experimental results further show that TIR‐YOLO‐ADAS performs favourably when compared with three representative detection algorithms. To evaluate the practicality and feasibility of the proposed framework in various applications, a qualitative assessment in real road scenarios was conducted. The experimental results confirm that the proposed framework performs promisingly and could be integrated into vehicle platforms as an ADAS module.

Abstract Bladder cancer ranks as the 10th most common cancer worldwide, with deteriorating prognosis as the disease advances. While immune checkpoint inhibitors (ICIs) have shown promise in clinical therapy in both operable and advanced bladder cancer, identifying patients who will respond is challenging. Anoikis, a specialized form of cell death that occurs when cells detach from the extracellular matrix, is closely linked to tumor progression. Here, we aimed to explore the anoikis-based biomarkers for bladder cancer prognosis and immunotherapeutic decisions. Through consensus clustering, we categorized patients from the TCGA-BLCA cohort into two clusters based on anoikis-related genes (ARGs). Significant differences in survival outcome, clinical features, tumor immune environment (TIME), and potential ICIs response were observed between clusters. We then formulated a four-gene signature, termed "Ascore", to encapsulate this gene expression pattern. The Ascore was found to be closely associated with survival outcome and served as an independent prognosticator in both the TCGA-BLCA cohort and the IMvigor210 cohort. It also demonstrated superior predictive capacity (AUC = 0.717) for bladder cancer immunotherapy response compared to biomarkers like TMB and PD-L1. Finally, we evaluated Ascore’s independent prognostic performance as a non-invasive biomarker in our clinical cohort (Gulou-Cohort1) using circulating tumor cells detection, achieving an AUC of 0.803. Another clinical cohort (Gulou-Cohort2) consisted of 40 patients undergoing neoadjuvant anti-PD-1 treatment was also examined. Immunohistochemistry of Ascore in these patients revealed its correlation with the pathological response to bladder cancer immunotherapy (P = 0.004). Impressively, Ascore (AUC = 0.913) surpassed PD-L1 (AUC = 0.662) in forecasting immunotherapy response and indicated better net benefit. In conclusion, our study introduces Ascore as a novel, robust prognostic biomarker for bladder cancer, offering a new tool for enhancing immunotherapy decisions and contributing to the tailored treatment approaches in this field.

Abstract Background Continuous and noninvasive hemoglobin (Hb) monitoring during surgery is essential for anesthesiologists to make transfusions decisions. The aim of this study was to investigate the feasibility and accuracy of noninvasive and continuous Hb monitoring using transesophageal descending aortic photoplethysmography (dPPG) in porcine model. Methods Nineteen landrace pigs, aged 3 to 5 months and weighing 30 to 50 kg, were enrolled in this study. A homemade oximetry sensor, including red (660 nm) and infrared (940 nm) lights, was placed in the esophagus for dPPG signal detection to pair with the corresponding reference Hb values (Hbi−STAT) measured by blood gas analysis. The decrease and increase changes in Hb concentration were achieved by hemodilution and transfusion. Metrics, including alternating current (AC), direct current (DC), and AC/DC for both red and infrared light were extracted from the dPPG signal. A receiver operating characteristic (ROC) curve was built to evaluate the performance of dPPG metrics in predicting the Hb “trigger threshold” of transfusion (Hb 100 g/L). Agreement and trending ability between Hb measured by dPPG (HbdPPG) and by blood gas analysis were analyzed by Bland-Altman method and polar plot graph. Error grid analysis was also performed to evaluate clinical significance of HbdPPG measurement. Results The dPPG signal was successfully detected in all of the enrolled experimental pigs, without the occurrence of a continuous loss of dPPG signal for 2 min during the entire measurement. A total of 376 pairs of dPPG signal and Hbi−STAT were acquired. ACred/DCred and ACinf/DCinf had moderate correlations with Hbi−STAT, and the correlation coefficients were 0.790 and 0.782, respectively. The areas under the ROC curve for ACred/DCred and ACinf/DCinf in predicting Hbi−STAT < 60 g/L were 0.85 and 0.75, in predicting Hbi−STAT > 100 g/L were 0.90 and 0.83, respectively. Bland-Altman analysis and polar plot showed a small bias (1.69 g/L) but a wide limit of agreement (-26.02–29.40 g/L) and a poor trend ability between HbdPPG and Hbi−STAT. Clinical significance analysis showed that 82% of the data lay within the Zone A, 18% within the Zone B, and 0% within the Zone C. Conclusion It is feasible to establish a noninvasive and continuous Hb monitoring by transesophageal dPPG signal. The ACred/DCred extracted from the dPPG signal could provide a sensitive prediction of the Hb threshold for transfusion. The Hb concentration measured by dPPG signal has a moderate correlation with that measured by blood gas analysis. This animal study may provide an experimental basis for the development of bedside HbdPPG monitoring in the future.

With the proliferation of urban video surveillance systems, the abundance of surveillance video data has emerged as a pivotal asset for enhancing public safety. Within these video archives, the identification of abnormal human actions carries profound implications for security incidents. Nevertheless, existing surveillance systems primarily rely on conventional algorithms, leading to both missed incidents and false alarms. To address the challenge of automating multi-object surveillance video analysis, this study introduces a comprehensive method for the detection and recognition of multi-object abnormal actions. This study comprises a two-stage framework: the coarse detection stage employs an enhanced YOWOv2E model for spatio-temporal action detection, while the precise detection stage utilizes a two-stream network for precise action classification. In parallel, this paper presents the PSA-Dataset to address the current limitations in the field of abnormal action detection. Experimental results, collected from both public datasets and a self-built dataset, illustrate the effectiveness of the proposed method in identifying a wide spectrum of abnormal actions. This work offers valuable insights for automating the analysis of human actions in videos pertaining to public security.

Objective The efficacy of sirolimus in treating severe or refractory systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, few studies focused on mild or moderate SLE. Therefore, in this study we elucidated clinical efficacy of add-on sirolimus in patients with mild or moderate SLE.Methods Data of 17 consecutive patients with SLE were retrospectively collected. SLE Disease Activity Index-2000 (SLEDAI-2K), clinical manifestation, laboratory data and peripheral T lymphocyte subsets with cytokines were collected before and 6 months after sirolimus add-on treatment. T cell subsets were detected by flow cytometry and cytokines were determined by multiplex bead-based flow fluorescent immunoassay simultaneously. Twenty healthy controls matched with age and sex were also included in our study.Results (1) The numbers of peripheral blood lymphocytes, T cells, T helper (Th) cells, regulatory T (Treg) cells, Th1 cells, Th2 cells and Treg/Th17 ratios in patients with SLE were significantly lower, while the numbers of Th17 cells were evidently higher than those of healthy control (p

Abstract Host immune systems serving as crucial defense lines are vital resisting mechanisms against biofilm‐associated implant infections. Nevertheless, biofilms hinder the penetration of anti‐bacterial species, inhibit phagocytosis of immune cells, and frustrate host inflammatory responses, ultimately resulting in the weakness of the host immune system for biofilm elimination. Herein, a cell‐like construct is developed through encapsulation of erythrocyte membrane fragments on the surface of Fe3O4 nanoparticle‐fabricated microbubbles and then loaded with hydroxyurea (EMB‐Hu). Under ultrasound (US) stimulation, EMB‐Hu undergoes a stable oscillation manner to act in an “exocytosis” mechanism for disrupting biofilm, releasing agents, and enhancing penetration of catalytically generated anti‐bacterial species within biofilms. Additionally, the US‐stimulated “exocytosis” by EMB‐Hu can activate pro‐inflammatory macrophage polarization and enhance macrophage phagocytosis for clearance of disrupted biofilms. Collectively, this work has exhibited cell‐like microbubbles with US‐stimulated “exocytosis” mechanisms to overcome the biofilm barrier and signal macrophages for inflammatory activation, finally achieving favorable therapeutic effects against implant infections caused by methicillin‐resistant Staphylococcus aureus (MRSA) biofilms.

Objective: Brown adipose tissue (BAT) development and function are essential for maintaining energy balance. However, the key factors that specifically regulate brown adipogenesis require further identification. Here, we demonstrated that the nuclear receptor subfamily 2 group F member 6 (NR2F6) played a pivotal role in brown adipogenesis and energy homeostasis. Methods: We examined the differentiation of immortalized brown adipocytes and primary brown adipocytes when NR2F6 were deleted, and explored the mechanism through which NR2F6 regulated adipogenesis using ChIP-qPCR in vitro. Male wild type (WT) and Pdgfra-Cre-mediated deletion of Nr2f6 in preadipocytes (NR2F6-PKO) mice were fed with high fat diet (HFD) for 12 weeks, and adiposity, glucose intolerance, insulin resistance and inflammation were assessed. Results: NR2F6 exhibited abundant expression in BAT, while its expression was minimal in white adipose tissue (WAT). Within BAT, NR2F6 was highly expressed in preadipocytes, experienced a transient increase in the early stage of brown adipocyte differentiation, and significantly decreased in the mature adipocytes. Depletion of NR2F6 in preadipocytes inhibited brown adipogenesis, caused hypertrophy of brown adipocytes, and impaired thermogenic function of BAT, but without affecting WAT development. NR2F6 transcriptionally regulated PPARγ expression to promote adipogenic process in brown adipocytes. Loss of NR2F6 in preadipocytes led to increased susceptibility to diet-induced metabolic disorders. Conclusions: Our findings unveiled NR2F6 as a novel key regulator of brown adipogenesis, potentially opening up new avenues for maintaining metabolic homeostasis by targeting NR2F6.

Abstract Lymph node (LN) metastasis is one of the key prognostic factors in bladder cancer, but its underlying mechanisms remain unclear. Here, we found that elevated expression of WD repeat domain 4 (WDR4) in bladder cancer correlated with worse prognosis. WDR4 can promote the LN metastasis and proliferation of bladder cancer cells. Mechanistic studies showed that WDR4 can promote the nuclear localization of DEAD-box helicase 20 (DDX20) and act as an adaptor to bind DDX20 and Early growth response 1 (Egr1), thereby inhibiting Egr1-promoted transcriptional expression of arrestin beta 2 (ARRB2) and ultimately contributing to the progression of bladder cancer. Immunohistochemical analysis confirmed that WDR4 expression is also an independent predictor of LN metastasis in bladder cancer. Our results reveal a novel mechanism of LN metastasis and progression in bladder cancer and identify WDR4 as a potential therapeutic target for metastatic bladder cancer.

Abstract Spatiotemporal traffic data usually suffers from missing entries in the data acquisition and transmission process. Existing imputation methods only consider the global/local structure of spatiotemporal traffic data, resulting in insufficient estimation performance. Fortunately, it is found that traffic data admits the nonlocal self‐similarity (NSS) prior. This paper incorporates the global and nonlocal low‐rank priors of traffic data and proposes a tensor completion model for spatiotemporal traffic data imputation. To be specific, the proposed method uses tensor ring (TR) decomposition with an enhanced representation capability to characterize the global low‐TR‐rank prior of traffic data, e.g. the correlation of sensor and time modes of the tensor (i.e. traffic data). An implicit plug‐and‐play (PnP)‐based regularization is further utilized to exploit the NSS prior, which depicts the nonlocal similar traffic data patterns. Furthermore, the proximal alternating minimization algorithm under the PnP framework is derived to solve this model. The experiment results on various datasets and missing scenarios show the superiority of the proposed model.

In recent years, there has been extensive research and application of unsupervised monocular depth estimation methods for intelligent vehicles. However, a major limitation of most existing approaches is their inability to predict absolute depth values in physical units, as they generally suffer from the scale problem. Furthermore, most research efforts have focused on ground vehicles, neglecting the potential application of these methods to unmanned aerial vehicles (UAVs). To address these gaps, this paper proposes a novel absolute depth estimation method specifically designed for flight scenes using a monocular vision sensor, in which a geometry-based scale recovery algorithm serves as a post-processing stage of relative depth estimation results with scale consistency. By exploiting the feature correspondence between successive images and using the pose data provided by equipped navigation sensors, the scale factor between relative and absolute scales is calculated according to a multi-view geometry model, and then absolute depth maps are generated by pixel-wise multiplication of relative depth maps with the scale factor. As a result, the unsupervised monocular depth estimation technology is extended from relative depth estimation in semi-structured scenes to absolute depth estimation in unstructured scenes. Experiments on the publicly available Mid-Air dataset and customized data demonstrate the effectiveness of our method in different cases and settings, as well as its robustness to navigation sensor noise. The proposed method only requires UAVs to be equipped with monocular camera and common navigation sensors, and the obtained absolute depth information can be directly used for downstream tasks, which is significant for this kind of vehicle that has rarely been explored in previous depth estimation studies.

Abstract Therapeutic tumor vaccines have attracted considerable attention in the past decade; they can induce tumor regression, eradicate minimal residual disease, establish lasting immune memory and avoid non-specific and adverse side effects. However, the challenge in the field of therapeutic tumor vaccines is ensuring the delivery of immune components to the lymph nodes (LNs) to activate immune cells. The clinical response rate of traditional therapeutic tumor vaccines falls short of expectations due to inadequate lymph node delivery. With the rapid development of nanotechnology, a large number of nanoplatform-based LN-targeting nanovaccines have been exploited for optimizing tumor immunotherapies. In addition, some nanovaccines possess non-invasive visualization performance, which is benefit for understanding the kinetics of nanovaccine exposure in LNs. Herein, we present the parameters of nanoplatforms, such as size, surface modification, shape, and deformability, which affect the LN-targeting functions of nanovaccines. The recent advances in nanoplatforms with different components promoting LN-targeting are also summarized. Furthermore, emerging LNs-targeting nanoplatform-mediated imaging strategies to both improve targeting performance and enhance the quality of LN imaging are discussed. Finally, we summarize the prospects and challenges of nanoplatform-based LN-targeting and /or imaging strategies, which optimize the clinical efficacy of nanovaccines in tumor immunotherapies.

Abstract The advent of drug-resistant pathogens results in the occurrence of stubborn bacterial infections that cannot be treated with traditional antibiotics. Antibacterial immunotherapy by reviving or activating the body’s immune system to eliminate pathogenic bacteria has confirmed promising therapeutic strategies in controlling bacterial infections. Subsequent studies found that antimicrobial immunotherapy has its own benefits and limitations, such as avoiding recurrence of infection and autoimmunity-induced side effects. Current studies indicate that the various antibacterial therapeutic strategies inducing immune regulation can achieve superior therapeutic efficacy compared with monotherapy alone. Therefore, summarizing the recent advances in nanomedicine with immunomodulatory functions for combating bacterial infections is necessary. Herein, we briefly introduce the crisis caused by drug-resistant bacteria and the opportunity for antibacterial immunotherapy. Then, immune-involved multimodal antibacterial therapy for the treatment of infectious diseases was systematically summarized. Finally, the prospects and challenges of immune-involved combinational therapy are discussed. Graphical Abstract

In recent years, an increasing number of reports have explored the wound healing mechanism of these two traditional Chinese herbal medicines- Panax ginseng and Panax notoginseng, but there is no systematic research on the related core functions and different mechanisms in the treatment of wound healing up to now. Based on network pharmacology and meta-analysis, the present work aimed to comprehensively review the commonality and diversity of P. ginseng and P. notoginseng in wound healing. In this study, a wound healing-related ''ingredients-targets'' network of two herbs was constructed. Thereafter, meta-analysis of the multiple target lists by Metascape showed that these two medicines significantly regulated blood vessel development, responses to cytokines and growth factors and oxygen levels, cell death, cell proliferation and differentiation, and cell adhesion. To better understand the discrepancy between these two herbs, it was found that common signaling pathways including Rap1, PI3K/AKT, MAPK, HIF-1 and Focal adhesion regulated the functions listed above. In parallel, the different pathways including renin-angiotensin system, RNA transport and circadian rhythm, autophagy, and the different metabolic pathways may also explained the discrepancies in the regulation of the above-mentioned functions, consistent with the Traditional Chinese Medicine theory about the effects of P. ginseng and P. notoginseng.

Abstract Background Microalgae are widely considered as multifunctional cell factories that are able to transform the photo-synthetically fixed CO2 to numerous high-value compounds, including lipids, carbohydrates, proteins and pigments. However, contamination of the algal mass culture with fungal parasites continues to threaten the production of algal biomass, which dramatically highlights the importance of developing effective measures to control the fungal infection. One viable solution is to identify potential metabolic pathways that are essential for fungal pathogenicity but are not obligate for algal growth, and to use inhibitors targeting such pathways to restrain the infection. However, such targets remain largely unknown, making it challenging to develop effective measures to mitigate the infection in algal mass culture. Results In the present study, we conducted RNA-Seq analysis for the fungus Paraphysoderma sedebokerense, which can infect the astaxanthin-producing microalga Haematococcus pluvialis. It was found that many differentially expressed genes (DEGs) related to folate-mediated one-carbon metabolism (FOCM) were enriched in P. sedebokerense, which was assumed to produce metabolites required for the fungal parasitism. To verify this hypothesis, antifolate that hampered FOCM was applied to the culture systems. Results showed that when 20 ppm of the antifolate co-trimoxazole were added, the infection ratio decreased to ~ 10% after 9 days inoculation (for the control, the infection ratio was 100% after 5 days inoculation). Moreover, application of co-trimoxazole to H. pluvialis mono-culture showed no obvious differences in the biomass and pigment accumulation compared with the control, suggesting that this is a potentially algae-safe, fungi-targeted treatment. Conclusions This study demonstrated that applying antifolate to H. pluvialis culturing systems can abolish the infection of the fungus P. sedebokerense and the treatment shows no obvious disturbance to the algal culture, suggesting FOCM is a potential target for antifungal drug design in the microalgal mass culture industry.

Abstract Solar-thermal storage with phase-change material (PCM) plays an important role in solar energy utilization. However, most PCMs own low thermal conductivity which restricts the thermal charging rate in bulk samples and leads to low solar-thermal conversion efficiency. Here, we propose to regulate the solar-thermal conversion interface in spatial dimension by transmitting the sunlight into the paraffin-graphene composite with side-glowing optical waveguide fiber. This inner-light-supply mode avoids the overheating surface of the PCM, accelerates the charging rate by 123% than that of the traditional surface irradiation mode and increases the solar thermal efficiency to ~94.85%. Additionally, the large-scale device with inner-light-supply mode works efficiently outdoors, indicating the potential of this heat localization strategy in practical application.

Abstract Diastolic dysfunction is a major cardiac dysfunction, and an important predisposing factor is age. Although exercise training is often used for the prevention and treatment of cardiovascular disease nowadays, little is currently known about whether exercise interventions associated with the slowing of cardiac aging are related to mtp‐related pathways. In the present study, the UAS/Tub‐Gal4 system was used to knockdown whole‐body mtp expression levels in Drosophila, which underwent 2 weeks of endurance training. By conducting different assays and quantifying different indicators, we sought to investigate the relationship between mtp, exercise, and age‐related diastolic dysfunction. We found that (1) Drosophila in the mtpRNAi youth group exhibited age‐related diastolic dysfunction and had a significantly shorter mean lifespan. (2) Endurance exercise could improve diastolic dysfunction and prolong lifespan in aged Drosophila. (3) Endurance exercise could increase the expression levels of apolpp and Acox3, and decrease the levels of TC, LDL‐C, and TG in the aged group. In summary, aging causes age‐associated diastolic dysfunction in Drosophila, and systemic knockdown of mtp causes premature age‐associated diastolic dysfunction in young Drosophila. Besides, endurance exercise improves age‐related diastolic dysfunction and prolongs lifespan.

ABSTRACTBackground Non-responsiveness is a major barrier in current cancer immune checkpoint blockade therapies, and the mechanism has not been elucidated yet. Therefore, it is necessary to discover the mechanism and biomarkers of tumor immunotherapeutic resistance.Methods Bioinformatics analysis was performed based on CD8+ T cell infiltration in multiple tumor databases to screen out genes related to anti-tumor immunity. Associations between Regulator of G-protein signaling 1 (RGS1) and IFNγ-STAT1 signaling, and MHCI antigen presentation pathway were examined by RT-qPCR, western blotting, and flow cytometry. The modulatory mechanisms of RGS1 were investigated via CHIP-qPCR and dual-luciferase assay. The clinical and therapeutic implications of RGS1 were comprehensively investigated using tumor cell lines, mouse models, and clinical samples receiving immunotherapy.Results RGS1 was identified as the highest gene positively correlated with immunogenicity among RGS family. Inhibition of RGS1 in neoplastic cells dampened anti-tumor immune response and elicited resistance to immunotherapy in both renal and lung murine subcutaneous tumors. Mechanistically, RGS1 enhanced the binding of activating transcription factor 3 (ATF3) to the promoter of interferon gamma receptor 1 (IFNGR1), activated STAT1 and the subsequent expression of IFNγ-inducible genes, especially CXCL9 and MHC class I (MHCI), thereby influenced CD8+ T cell infiltration and antigen presentation and processing. Clinically, lower expression level of RGS1 was associated with resistance of PD1 inhibition therapy and shortened progression-free survival among 21 NSCLC patients receiving immunotherapy.Conclusions Together, these findings uncover a novel mechanism that elicits immunotherapy resistance and highlight the function of tumor-intrinsic RGS1, which brings new insights for future strategies to sensitize anti-PD1 immunotherapy.

The specific mechanism of clear cell renal cell carcinoma (ccRCC) progression, a pathological type that accounts for the highest proportion of RCC, remains unclear. In this study, bioinformatics analysis of scRNA-seq dataset in ccRCC revealed that MIOX was a gene specifically down-regulated in tumor epithelial cells of ccRCC. Analysis of the TCGA database further validated the association between decreased MIOX mRNA levels and ccRCC malignant phenotype and poor prognosis. Immunohistochemistry indicated the down-regulation of MIOX in ccRCC tissues compared to paired adjacent renal tissues, with further down-regulation of MIOX in the primary tumors of patients with primary metastasis compared to those without metastasis. Also, patients with low expression of MIOX showed shorter metastasis-free survival (MFS) compared to those with high MIOX expression. In vitro results showed that overexpression of MIOX in ccRCC cells inhibited the proliferation, migration and invasion and promoted apoptosis. Mechanistically, up-regulation of MIOX inhibited autophagy to elevate the levels of ROS, and thus suppressed STAT3/c-Myc-mediated epithelial-mesenchymal transition in ccRCC cells. In vivo data further confirmed that increased MIOX expression suppressed the growth and proliferation of RCC cells and reduced the ability of RCC cells to form metastases in the lung. This study demonstrates that MIOX is an important regulatory molecule of ccRCC, which is conducive to understanding the potential molecular mechanism of ccRCC progression.

ABSTRACTIn the past several decades, noble metal nanoclusters (NMNCs) have been developed as an emerging class of luminescent materials due to their superior photo-stability and biocompatibility, but their luminous quantum yield is relatively low and the physical origin of the bright photoluminescence (PL) of NMNCs remain elusive, which limited their practical application. As the well-defined structure and composition of NMNCs have been determined, in this mini-review, the effect of each component (metal core, ligand shell and interfacial water) on their PL properties and corresponded working mechanism were comprehensively introduced, and a model that structural water molecules dominated p band intermediate state was proposed to give a unified understanding on the PL mechanism of NMNCs and a further perspective to the future developments of NMNCs by revisiting the development of our studies on the PL mechanism of NMNCs in the past decade.

Efficiently removing clouds from remote sensing imagery presents a significant challenge, yet it is crucial for a variety of applications. This paper introduces a novel sparse function, named the tri-fiber-wise sparse function, meticulously engineered for the targeted tasks of cloud detection and removal. This function is adept at capturing cloud characteristics across three dimensions, leveraging the sparsity of mode-1, -2, and -3 fibers simultaneously to achieve precise cloud detection. By incorporating the concept of tensor multi-rank, which describes the global correlation, we have developed a tri-fiber-wise sparse-based model that excels in both detecting and eliminating clouds from images. Furthermore, to ensure that the cloud-free information accurately matches the corresponding areas in the observed data, we have enhanced our model with an extended box-constraint strategy. The experiments showcase the notable success of the proposed method in cloud removal. This highlights its potential and utility in enhancing the accuracy of remote sensing imagery.

Objectives We conducted a systematic review and meta-analysis to determine the efficacy of non-conventional synthetic disease-modifying antirheumatic drug (ncs-DMARD) strategies on patients with rheumatoid arthritis (RA)-associated interstitial lung disease (ILD).Methods PubMed, EMBASE, the Cochrane Library and Web of Science were searched for relevant articles from inception to 1 June 2022. The results obtained from the analysis were expressed as mean difference (MD), effect size and 95% CI.Results A total of 17 studies, including 1315 patients with RA-ILD, were eligible. The ncs-DMARDs included abatacept, rituximab, tocilizumab, tumour necrosis factor and Janus kinase inhibitors. Compared with the baseline, there were no significant changes in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and diffusion lung capacity for carbon monoxide (DLCO) values in the pooled data after ncs-DMARD treatment (alone or combined with conventional therapy) (p=0.36 for FVC; p=0.96 for FEV1 and p=0.46 for DLCO). Of note, FVC was obviously increased in rituximab subgroup (MD=−4.62, 95% CI −8.90 to −0.33, p=0.03). Also, high-resolution CT non-progression rate and fatality rate due to ILD progression in patients with RA-ILD were 0.792 (95% CI 0.746 to 0.834, p=0.015) and 0.049 (95% CI 0.035 to 0.065, p=0.000), respectively.Conclusion ncs-DMARDs alone or combined with conventional therapy might be an optimal and promising treatment for stabilising or improving ILD in patients with RA-ILD.PROSPERO registration number CRD42022356816.

Docetaxel (DTX) plays an important role in treating advanced prostate cancer (PCa). However, nearly all patients receiving DTX therapy ultimately progress to DTX resistance. How to address DTX resistance in PCa remains a key challenge for all urologists. Small ankyrin 1 (sAnk1) is an integral membrane protein in the endoplasmic reticulum. In the present study, we identified that sAnk1 is upregulated in PCa tissues and is positively associated with DTX therapy resistance in PCa. Further investigation demonstrated that overexpression of sAnk1 can significantly increase the DTX‐resistant ability of PCa cells in vitro and in vivo. In addition, overexpression of sAnk1 could enhance oxidative phosphorylation (OXPHOS) levels in PCa cells, which was consistent with the higher OXPHOS levels observed in DTX‐resistant PCa cells as compared to DTX‐sensitive PCa cells. sAnk1 was also found to interact with polypyrimidine‐tract‐binding protein (PTBP1), an alternative splicing factor, and suppressed PTBP1‐mediated alternative splicing of the pyruvate kinase gene (PKM). Thus, overexpression of sAnk1 decreased the ratio of PKM2/PKM1, enhanced the OXPHOS level, and ultimately promoted the resistance of PCa cells to DTX. In summary, our data suggest that sAnk1 enhances DTX resistance in PCa cells.

The block-term tensor decomposition model with multilinear rank-$(L_{r},L_{r},1)$ terms (or the “${\mathsf{LL1}}$ tensor decomposition” in short) offers a valuable alternative formulation for hyperspectral unmixing (HU), which ensures the identifiability of the endmembers/abundances in cases where classic matrix factorization (MF) approaches cannot provide such guarantees. However, the existing ${\mathsf{LL1}}$-tensor-decomposition-based HU algorithms use a three-factor parameterization of the tensor (i.e., the hyperspectral image cube), which causes difficulties in incorporating structural prior information arising in HU. Consequently, their algorithms often exhibit high per-iteration complexity and slow convergence. This article focuses on ${\mathsf{LL1}}$ tensor decomposition under structural constraints and regularization terms in HU. Our algorithm uses a two-factor reparameterization of the tensor model. Like in the MF-based approaches, the factors correspond to the endmembers and abundances in the context of HU. Thus, the proposed framework is natural to incorporate physics-motivated priors in HU. To tackle the formulated optimization problem, a two-block alternating gradient projection (GP)-based algorithm is proposed. Carefully designed projection solvers are proposed to implement the GP algorithm with a relatively low per-iteration complexity. An extrapolation-based acceleration strategy is proposed to expedite the GP algorithm. Such an extrapolated multiblock algorithm only had asymptotic convergence assurances in the literature. Our analysis shows that the algorithm converges to the vicinity of a stationary point within finite iterations, under reasonable conditions. Empirical study shows that the proposed algorithm often attains orders-of-magnitude speedup and substantial HU performance gains compared with the existing ${\mathsf{LL1}}$-decomposition-based HU algorithms.

Abstract Background At present, there are multiple hypotheses regarding the mechanisms underlying the effect of exercise on the postoperative inflammatory factors and the IGF system among breast cancer patients, especially. To determine the underlying mechanisms, prevent the recurrence of breast cancer and improve its prognosis, this paper will systematically evaluate the impact of exercise on inflammatory factors and the IGF system in breast cancer survivors. Methods The PubMed, Embase, Web of Science, CNKI, Wanfang and VIP (Chinese scientific and technical journals) databases were systematically searched until April 2021. The search terms included 'exercise', 'inflammatory factor', 'IGF system' and 'breast cancer'. A total of 1066 relevant articles were retrieved. The articles were screened according to inclusion and exclusion criteria, such as study population, intervention method and type of experiment, and 11 articles were ultimately included. All statistical results were analysed using STATA 14.0 and Rstudio 4.1.1. Results We found that exercise significantly reduced the level of IGF-1 (WMD, -19.947 ng/ml; 95% CI, -22.669 to -17.225; P = 0.000). Subgroup analysis showed that in the studies with an intervention period > 12 weeks, exercise significantly reduced IL-6 levels (WMD, -0.761 pg/ml; 95% CI, -1.369 to -0.153; p = 0.014), while in the studies with an intervention period ≤ 12 weeks, exercise significantly reduced CRP (WMD, -2.381 mg/L; 95% CI, -4.835 to 0.073, P = 0.001) and IL-10 levels (WMD, -7.141 pg/ml, 95% CI, -10.853 to -3.428; P = 0.000). In addition, aerobic exercise plus resistance training significantly reduced IL-6 levels (WMD, -1.474 pg/ml; 95% CI, -1.653 to -1.296; P = 0.000). The results of the sensitivity analysis showed that after excluding the studies with high heterogeneity, exercise significantly reduced the TNF-α levels in patients with breast cancer (WMD, -1.399 pg/ml; 95% CI, -1.718 to -1.080; P = 0.000). Conclusion Exercise reduces the postoperative levels of IGF-1, IL-6, CRP, IL-10 and TNF-α among patients with breast cancer, which may have a significant impact on inhibiting breast cancer recurrence and improving its prognosis. Future studies should examine the effects of different durations and types of exercise to develop individualized exercise prescriptions for breast cancer patients.

Objective The aim of the meta-analysis was to explore effects of resistance exercise (RE) on body composition and physical function in patients with prostate cancer (PCa).Data sources We searched the electronic databases of Pubmed, Embase, Cochrane, and web of science. Published studies have been collected from these databases. Search terms include resistance training, strength training, RE, androgen suppression therapy, androgen deprivation therapy and PCa, with a deadline of 31 March 2022.Main results These studies showed significant improvements of body composition(Lean body mass MD: 1.12 95% CI [0.48, 1.76], p 0.05), 400 m walk (MD: –21.74 95% CI [–45.53, 2.05], p > 0.05) and times up and go (MD: –0.50 95% CI [–1.03, 0.03], p > 0.05) were not obvious. Subgroup analyses showed that RE for ≥ 6 months (compared with RE intervention for < 6 months) and starting exercise immediately after androgen deprivation therapy (ADT) (compared with delayed exercise after ADT) resulted in more significant improvements in body composition. Furthermore, the results showed that the exercise intensity of 8–12 RM significantly improved body composition.Conclusions RE seems to be a promising approach in order to improve body composition and physical function in PCa patients to offset their treatment-related side effects. RE should be used as a means of rehabilitation and care for PCa. Starting exercise immediately after ADT and extending exercise time while choosing the right intensity can better improve the patients’ body composition and function. Registration number INPLASY202280019

Abstract The mechanisms underlying the effects of cancer-associated fibroblasts (CAFs) on cancer stemness and tumor progression in renal cell carcinoma (RCC) have not been elucidated yet. In the present study, we found that the enrichment of CAFs was positively associated with tumor progression and cancer stemness in RCC. Further investigation revealed that CAFs could enhance cancer stemness through delivering exosomes to RCC cells, and miR-181d-5p was identified as the critical exosomal miRNA in CAF-secreted exosomes by small RNA sequencing and subsequent screening assays. Mechanistically, exosomal miR-181d-5p transferred from CAFs to RCC cells directly suppressed the expression of ring finger protein 43 (RNF43) and activated Wnt/β-catenin signaling pathway, thus promoted cancer stemness and tumor progression. Overexpression of RNF43 strongly suppressed stemness properties and the effects could be reverted by miR-181d-5p. Overall, our findings revealed a crucial mechanism by which CAF-secreted exosomal miRNAs to enhance cancer stemness and thus promote RCC progression, suggesting a new avenue based on CAF-secreted miRNAs for more effective targeted therapies.

Abstract Background Angong Niuhuang Pill (ANP), a renowned precious traditional Chinese medicine prescription, is extensively utilized for the clinical treatment of stroke, meningitis and encephalorrhagia in China. As a classic resuscitation-inducing aromatic prescription, ANP has been investigated for its pharmacological effects in recent years, while the volatile composition in ANP still lacks comprehensive elucidation. Method To better explore the volatile constituents in ANP, a qualitative analysis method was developed based on gas chromatography coupled with mass spectrometry. Furthermore, a validated quantitative method was established to determine 21 main compounds in 8 batches of commercially available ANP samples by gas chromatography-tandem mass spectrometry. The quantitative data were successively subjected to Pearson correlation coefficient analysis. Additionally, the absorbed volatile constituents in rat plasma after single oral administration of ANP have also been characterized. Results A total of 93 volatile constituents including 29 sesquiterpenoids, 28 monoterpenoids, 13 fatty acids and their esters, 7 alkanes, 6 ketones, 3 phenols, 3 aldehydes, 2 benzoate esters, and 2 other types, were preliminarily characterized, which primarily originated from Borneolum, Moschus, Curcumae Radix, and Gardeniae Fructus. d-Borneol, isoborneol and muscone were the top three abundant ingredients (> 600 μg/g) in 8 batches of ANP samples. Subsequently, the average Pearson correlation coefficient of the contents of 21 analytes was 0.993, inferring the high batch-to-batch similarity among 8 batches. After oral administration of ANP, d-borneol, isoborneol, muscone and camphor were the main volatile constituents absorbed in the rat plasma. Conclusion This research may be helpful for the comprehensive quality control study of ANP, and provide for guarantee the clinical efficacy of ANP.

Abstract Dendritic cell (DC)‐based cancer immunotherapy has exhibited remarkable clinical prospects because DCs play a central role in initiating and regulating adaptive immune responses. However, the application of traditional DC‐mediated immunotherapy is limited due to insufficient antigen delivery, inadequate antigen presentation, and high levels of immunosuppression. To address these challenges, engineered biomaterials have been exploited to enhance DC‐mediated immunotherapeutic effects. In this review, vital principal components that can enhance DC‐mediated immunotherapeutic effects are first introduced. The parameters considered in the rational design of biomaterials, including targeting modifications, size, shape, surface, and mechanical properties, which can affect biomaterial optimization of DC functions, are further summarized. Moreover, recent applications of various engineered biomaterials in the field of DC‐mediated immunotherapy are reviewed, including those serve as immune component delivery platforms, remodel the tumor microenvironment, and synergistically enhance the effects of other antitumor therapies. Overall, the present review comprehensively and systematically summarizes biomaterials related to the promotion of DC functions; and specifically focuses on the recent advances in biomaterial designs for DC activation to eradicate tumors. The challenges and opportunities of treatment strategies designed to amplify DCs via the application of biomaterials are discussed with the aim of inspiring the clinical translation of future DC‐mediated cancer immunotherapies.

PurposeBreast cancer is one of the most common malignant cancers in women, seriously endangering the physical and mental health of patients. In this study, we developed an app for breast cancer patients undergoing radiotherapy or chemotherapy with a focus on exercise interventions, supplemented by nutritional and psychological interventions, to verify the applicability of the app for these patients and its impact on their quality of life, sleep, and psychological state. We also investigated the patients’ experience and perceptions of the app.MethodsA total of 17 participants, aged 42–58 years, were recruited for this study using a mixed-methods design, including quantitative group pre-and post-test scores and qualitative interview results. The participants used the app for 8–18 weeks depending on their radiotherapy or chemotherapy cycle. During the radiotherapy or chemotherapy period, the participants used the “Yun Dong Ru Kang” exercise rehabilitation app to perform aerobic exercises twice a week, as well as rehabilitation exercises appropriate to their radiotherapy or chemotherapy stage, and used the app on their own the rest of the time. The primary results included their scores on the PSSUQ overall assessment usability questionnaire, the users’ use of the app, and the results of the interviews; the secondary indicators were quality of life, sleep status, and anxiety and depression status.ResultsAn overall score of 6.2 (out of 7 points) on the PSSUQ questionnaire indicates the high usability; the average use time per subject per week was 97.69 ± 11.82 min, which exceeds the minimum use time, but the average use time tended to decrease as the use time was postponed. Promoted articles on nutritional diets received the most hits. The results of the interviews were consistent with the questionnaire scores, with the majority of participants believing that the means of exercise should be enriched and the interface optimized, while the reduction in the length of use was related to the participants’ own state of learning about calisthenics. In the results of the Breast Cancer-Specific Scale FACT-B, there was a significant increase (p

Abstract Background Reducing postoperative pain due to the thoracotomy incisions in patients undergoing transapical transcatheter aortic valve implantation remains a challenge. Methods We introduced ultrasound-guided serratus anterior plane block (SAPB) in a patient with severe aortic insufficiency and chronic obstructive pulmonary disease before surgical intervention. Results The patient’s postoperative 1 h, 4 h, and 12 h resting visual analogue scale scores were 3, 1, and 1 without single injection of morphine or dezocine for rescue analgesia. Conclusions Ultrasound-guided SAPB could improve analgesia after transapical transcatheter aortic valve implantation.

Abstract Background At present, there is a lack of direct evidence to confirm whether the recommendations of the World Health Organization can play a role in fitness and disease prevention in the Chinese population. Therefore, we aimed to analyse 7-year longitudinal survey data to explore whether the physical activity volume recommended by the World Health Organization can help Chinese middle-aged and elderly people reduce the risk of heart disease. Methods Data for the 8327 participants who were finally included in this study were derived from the 7-year data of the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018. The physical activity volume is expressed by the product of physical frequency and duration, and heart disease is screened according to self-reported diagnosis and related treatment. The relationship between different physical activity volume groups and the incidence rate of heart disease was determined by a multivariate Cox proportional hazards regression model. Results After adjusting for all covariates, participants meeting the WHO’s recommendations had a 20% lower risk of heart disease than those who did not meet the WHO’s recommendations (HR = 0.80, 95% = 0.68–0.96). Subgroup analysis showed that among the participants meeting the WHO’s recommendations, men (HR = 0.71) had a lower risk of heart disease than women (HR = 0.74); in addition, the risk of heart disease was significantly reduced in participants who were middle-aged (26%), had a normal BMI range (49%), did not have hypertension (24%), did not have hyperlipidaemia (21%) and did not have lung disease (21%). It should be noted that the risk of heart disease was reduced by 72 and 67% in participants with untreated hyperlipidaemia and untreated lung disease, respectively. Conclusions This study revealed that meeting the WHO’s recommendations for physical activity volume can reduce the risk of heart disease in middle-aged and older people in China and can also effectively prevent heart disease for people with some common chronic diseases, such as hyperlipidaemia and lung disease. The results showed that physical activity for leisure and exercise had a lower preventive effect on heart disease than physical activity for a job, which may be related to the inappropriate leisure and exercise methods of the participants. Trial registration IRB00001052–11015.

Abstract Background Bladder cancer is the most common malignant tumor of the urinary system. Surgical resection and chemotherapy are the two mainstream treatments for bladder cancer. However, the outcomes are not satisfactory for patients with advanced bladder cancer. There is a need to further explore more effective targeted therapeutic strategies. Methods Proteomics were performed to compare protein expression differences between human bladder cancer tissues and adjacent normal tissues. The function of GPD1 on bladder cancer cells were confirmed through in vivo and in vitro assays. Transcriptomics and metabolomics were performed to reveal the underlying mechanisms of GPD1. Virtual screening was used to identify allosteric activator of GPD1. Results Here, we used proteomics to find that GPD1 expression was at low levels in bladder cancer tissues. Further investigation showed that GPD1 overexpression significantly promoted apoptosis in bladder cancer cells. Based on transcriptomics and metabolomics, GPD1 promotes Ca2+ influx and apoptosis of tumor cells via the lysoPC-PAFR-TRPV2 axis. Finally, we performed a virtual screening to obtain the GPD1 allosteric activator wedelolactone and demonstrated its ability to inhibit bladder tumor growth in vitro and in vivo. Conclusions This study suggests that GPD1 may act as a novel tumor suppressor in bladder cancer. Pharmacological activation of GPD1 is a potential therapeutic approach for bladder cancer.

The mechanisms that confer lung-specific metastasis in renal cell carcinomas (RCC) remain to be detailed. Here the authors show that LAPTM5 contributes to lung-specific metastasis of RCCs by suppressing BMP signalling and thus, enhancing self-renewal and cancer stem cell-like traits of RCCs.

Abstract Immunotherapy has emerged as a robust clinical strategy for cancer treatment. PD1/PD-L1 inhibitors have been used as second-line therapy for urothelial carcinoma due to the high tumor mutational burden. Despite the efficacy of the treatment is significant, the response rate is still poor. The tumor immune microenvironment plays a key role in the regulation of immunotherapeutic efficacy. However, a comprehensive understanding of the intricate microenvironment in clinical samples remains unclear. To obtain detailed systematic tumor immune profile, we performed an in-depth immunoassay on 12 human urothelial carcinoma tissue samples and 14 paratumor tissue samples using mass cytometry. Among the large number of cells assayed, we identified 71 T-cell phenotypes, 30 tumor-associated macrophage phenotypes. T cell marker expression profiles showed that almost all T cells in the tumor tissue were in a state of exhaustion. CD38 expression on tumor-associated macrophages (TAMs) was significantly higher than PDL1, and CD38+ TAMs were closely associated with immunosuppression. CD38 may be a more suitable target for immunotherapy in urothelial carcinoma compared to PD1/PDL1. This single-cell analysis of clinical samples expands our insights into the immune microenvironment of urothelial carcinoma and reveals potential biomarkers and targets for immunotherapy development.

Abstract In an electrocatalytic process, the cognition of the active phase in a catalyst has been regarded as one of the most vital issues, which not only boosts the fundamental understanding of the reaction procedure but also guides the engineering and design for further promising catalysts. Here, based on the oxygen evolution reaction (OER), the stepwise evolution of the dominant active phase is demonstrated in the LaNiO3 (LNO) catalyst once the single‐crystal thin film is decorated by LNO nanoparticles. It is found that the OER performance can be dramatically improved by this decoration, and the catalytic current density at 1.65 V can be enhanced by ≈1000% via ≈109 cm−2 nanoparticle adhesion after extracting the contribution of surface enlargement. Most importantly, a transition of the active phase from LNO to NiOOH via surface reconstruction with the density of LNO nanoparticles is demonstrated. Several mechanisms in terms of this active phase transition are discussed involving lattice orientation‐induced change of the surface energy profile, the lattice oxygen participation, and the A/B‐site ions leaching during OER cycles. This study suggests that the active phases in transition metal‐based OER catalysts can transform with morphology, which should be corresponding to distinct engineering strategies.

With the widespread prevalence of drug-resistant pathogens, traditional antibiotics have limited effectiveness and do not yield the desired outcomes. Recently, alternative antibacterial therapies based on ultrasound (US) have been explored to overcome the crisis of bacterial pathogens. Antimicrobial sonodynamic therapy (aSDT) offers an excellent solution that relies on US irradiation to produce reactive oxygen species (ROS) and achieve antibiotic-free mediated antimicrobial effects. In addition, aSDT possesses the advantage of superior tissue penetrability of US compared to light irradiation, demonstrating great feasibility in treating deep infections. Although existing conventional sonosensitizers can produce ROS for antimicrobial activity, some limitations, such as low penetration rate, nonspecific distribution and poor ROS production under hypoxic conditions, result in suboptimal sterilization in aSDT. Recently, emerging nanosonosensitizers have enormous advantages as high-performance agents in aSDT, which overcome the deficiencies of conventional sonosensitizers as described above. Thus, nanosonosensitizer-mediated aSDT has a bright future for the management of bacterial infections. This review classifies the current available nanosonosensitizers and provides an overview of the mechanisms, biomedical applications, recent advances and perspectives of aSDT.

Hypoxia is a negative prognostic indicator of solid tumors, which not only changes the survival state of tumors and increases their invasiveness but also remarkably reduces the sensitivity of tumors to treatments such as radiotherapy, chemotherapy and photodynamic therapy. Thus, developing therapeutic strategies to alleviate tumor hypoxia has recently been considered an extremely valuable target in oncology. In this review, nanotechnological strategies to elevate oxygen levels in tumor therapy in recent years are summarized, including (I) improving the hypoxic tumor microenvironment, (II) oxygen delivery to hypoxic tumors, and (III) oxygen generation in hypoxic tumors. Finally, the challenges and prospects of these nanotechnological strategies for alleviating tumor hypoxia are presented.

Shexiang Xintongning tablet (SXXTN) is a traditional Chinese medicine (TCM) preparation for the treatment of coronary heart disease (CHD) angina pectoris. However, due to the complexity of the compounds in SXXTN, the active chemical components responsible for the therapeutic effect are still ambiguous. The purpose of our study was to characterize the chemical profile of SXXTN and quantify the representative chemicals. The high-performance liquid chromatography coupled with time-of-flight mass spectrometry (HPLC-QTOF MS) method and gas chromatograph coupled with mass spectrometry (GC–MS) method were utilized to identify the chemical constituents of SXXTN. A total of 140 compounds including alkaloids, ginsenosides, organic acids, esters, triterpenes, phthalides and amino acid were identified in accordance with their retention times, accurate masses and characteristic MS/MS fragment patterns. Forty-four volatile components were characterized by GC–MS through NIST database matching. In the further research of quantitative analysis, 40 non-volatile compounds and 17 volatile compounds were determined and successfully applied for detecting in 7 batches of SXXTN samples by high performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (HPLC-QQQ MS) and gas chromatograph coupled with triple-quadrupole tandem mass spectrometry (GC-QQQ MS) in multiple reaction monitoring (MRM) mode, respectively. The quantitative methods were verified in linearity, precision, repeatability stability and recovery. The above results indicated that the established method was practical and reliable for synthetical quality evaluation of SXXTN. In addition, our study might supplement the chemical evidence for disclosing the material basis of its therapeutic effects.

Abstract Lymph node (LN) metastasis is associated with unfavorable prognosis of bladder cancer (BCa). Although lymphangiogenesis is functionally important in LN metastasis of tumors, the potential mechanism in BCa remains unclear. Here, we clarified a regulatory mechanism of circRNA-mediated lymphangiogenesis and LN metastasis in BCa based on next-generation sequencing data. We revealed that circDHTKD1 was positively associated with LN metastasis and significantly upregulated in BCa. By analyzing the co-expression patterns of circDHTKD1 and differentially expressed mRNAs, we identified that circDHTKD1 facilitated lymphangiogenesis by upregulating CXCL5. Mechanistically, circDHTKD1 directly interacted with miR-149-5p, and antagonized the repression of miR-149-5p on CXCL5. Furthermore, circDHTKD1-induced CXCL5 expression recruited and activated neutrophils, which participated in lymphangiogenesis by secreting VEGF-C. Our study supports circDHTKD1 as a promising diagnostic and therapeutic target for LN metastasis in BCa.

Abstract Background Moschus is a rare and precious natural medicine. Due to the properties of resources scarcity and expensive price of natural musk, artificial musk has been developed as substitute materials in some prescriptions. Rapid and accurate identification of natural or artificial musk in complex traditional Chinese medicine (TCM) preparations is also a challenge. Method A strategy from non-targeted to targeted gas chromatography-mass spectrometry (GC–MS) metabolomics was developed for discrimination of natural and artificial musk. Firstly, GC–MS-based non-targeted analysis combined with chemometrics was used to find the potential chemical markers to distinguish natural musk and artificial musk. Subsequently, targeted metabolomics was used to analyze musk in preparations with multiple reaction monitoring (MRM) mode by use gas chromatography coupled with triple quadrupole mass spectrometry (GC-QQQ MS). Results Two chemical markers named prasterone and androsterone have been selected and could be detected in all Compound Pien Tze Huang preparations (CPZHs) containing artificial musk, while the CPZHs containing natural musk did not detect two markers with S/N (signal to noise ratio) less than 3. Conclusion Our work provides an applicable approach to select the practical chemical markers for the assessment of musk in preparations to realize the traceability of musk in TCM and improve the quality control of musk-containing preparations.

Abstract Background Emerging evidence suggests that LMNB1 is involved in the development of multiple cancer types. However, there is no study reporting the potential role of LMNB1 in a systematic pan-cancer manner. Methods The gene expression level and potential oncogenic roles of LMNB1 in The Cancer Genome Atlas (TCGA) database were analyzed with Tumor Immune Estimation Resource version 2 (TIMER2.0), Gene Expression Profiling Interactive Analysis version 2 (GEPIA2), UALCAN and Sangerbox tools. Pathway enrichment analysis was carried out to explore the possible mechanism of LMNB1 on tumorigenesis and tumor progression. The therapeutic effects of LMNB1 knockdown combined with PARP inhibition on human cancers were further investigated in vitro. Results LMNB1 upregulation is generally observed in the tumor tissues of most TCGA cancer types, and is verified in kidney renal clear cell carcinoma using clinical specimens of our institute. High level of LMNB1 expression usually predicts poor overall survival and disease free survival for patients with tumors. Mechanically, LMNB1 level is positively correlated with CD4+ Th2 cell infiltration and DNA homologous recombination repair gene expression. In vitro experiments reveal that targeting LMNB1 has a synergistic effect on prostate cancer with PARP inhibitor treatment. Conclusions LMNB1 is a biomarker of CD4+ Th2 cell infiltration and DNA homologous recombination repair in human cancers. Blockage of LMNB1 combined with PARP inhibitor treatment could be a promising therapeutic strategy for patients with cancers.

Abstract Background Systemic sclerosis (SSc) is an autoimmune disease with high morbidity and mortality characterized by fibrosis of the skin and internal organs. Some studies have investigated the use of stem cells to treat SSc. Herein, a systematic review and meta-analysis was conducted to determine the efficacy and safety of mesenchymal stem cells (MSCs) in the treatment of SSc. Methods PubMed, Embase, Cochrane Library, Web of Science, OVID, China National Knowledge Infrastructure and Wanfang databases were searched up to February 1, 2021. Literature screening, data extraction and quality assessment were conducted independently by two researchers in according to the inclusion and exclusion criteria. The discrepancies were resolved by a third researcher. Results A total of 9 studies encompassing 133 SSc patients were included in the study. Compared to the baseline after treatment with MSCs: 1. The modified Rodnan skin score (mRSS) was significantly reduced in patients with SSc (P

Obesity is a prevalent metabolic disorder associated with various diseases, including cardiovascular conditions. While exercise is recognized as an effective approach for preventing and treating obesity, its underlying molecular mechanisms remain unclear. This study aimed to explore the impact of regular exercise on high-fat-diet-induced obesity and cardiac dysfunction in Drosophila, shedding light on its molecular mechanisms by identifying its regulation of the dfoxo and dsrebp signaling pathways. Our findings demonstrated that a high-fat diet leads to weight gain, fat accumulation, reduced climbing performance, and elevated triglyceride levels in Drosophila. Additionally, cardiac microfilaments in these flies exhibited irregularities, breakages, and shortening. M-mode analysis revealed that high-fat-diet-fed Drosophila displayed increased heart rates, shortened cardiac cycles, decreased systolic intervals, heightened arrhythmia indices, reduced diastolic diameters, and diminished fractional shortening. Remarkably, regular exercise effectively ameliorated these adverse outcomes. Further analysis showed that regular exercise reduced fat synthesis, promoted lipolysis, and mitigated high-fat-diet-induced cardiac dysfunction in Drosophila. These results suggest that regular exercise may mitigate high-fat-diet-induced obesity and cardiac dysfunction in Drosophila by regulating the dfoxo and dsrebp signaling pathways, offering valuable insights into the mechanisms underlying the beneficial effects of exercise on obesity and cardiac dysfunction induced by a high-fat diet.

In this paper, the anti-cancer activity and molecular mechanisms of the isomers of AD-1 and AD-2 (20(R)-AD-1, 20(R)-AD-2, 20(S)-AD-1 and 20(S)-AD-2) were investigated. The results indicated that all of the four compounds obviously suppressed the viability of various cancer cells, and the anti-cancer activity of 20(R)-AD-1 and 20(R)-AD-2 was significantly better than 20(S)-AD-1 and 20(S)-AD-2, especially for gastric cancer cells (BGC-803). Then, the differences in the anti-cancer mechanisms of the isomers were investigated. The data showed that 20(R)-AD-1 and 20(R)-AD-2 induced apoptosis and decreased MMP, up-regulated the expression of cytochrome C in cytosol, transferred Bax to the mitochondria, suppressed oxidative phosphorylation and glycolysis and stimulated reactive oxygen species (ROS) production. Apoptosis can be attenuated by the reactive oxygen species scavenger N-acetylcysteine. However, 20(S)-AD-1 and 20(S)-AD-2 barely exhibited the same results. The results indicated that 20(R)-AD-1 and 20(R)-AD-2 suppressed cellular energy metabolism and caused apoptosis through the mitochondrial pathway, which ROS generation was probably involved in. Above all, the data support the development of 20(R)-AD-1 and 20(R)-AD-2 as potential agents for human gastric carcinoma therapy.

In this paper, three kinds of rosin-based macroporous adsorption resins with carboxyl group (-COOH), ester group (-OR) and hydroxyl group (-OH) were synthesized. The adsorption characteristics of the three resins for Panax notoginseng saponins were investigated by static adsorption method. The results showed that the adsorption effect of the macroporous resin with -COOH as functional group was the best, the adsorption process accorded with the Langmuir model, and the adsorption kinetics was more consistent with the quasi-second order equation, the adsorption thermodynamic parameters ΔS was 159.46 J·mol−1·K−1, ΔH was 30.73 kJ·mol−1, indicating that the adsorption was a spontaneous endothermic process driven by entropy. When Panax notoginseng saponins were desorbed with 40% ethanol, the purity of Panax notoginseng saponins could be increased from 35.37% to 74.56%. The adsorption capacity of the resin was almost unchanged after being reused for 10 times. Through quantum chemical calculation, it was proved that the excellent performance of the macroporous adsorption resin with-COOH as functional group in the adsorption of Panax notoginseng saponins was mainly due to the role of hydrogen bond. The cytotoxicity test showed that the resin was safe and environmentally friendly, and the safety of the resin was better than that of the commercial resin D-101. Therefore, the prepared rosin-based macroporous resin with carboxyl groups was suitable for the separation and purification of Panax notoginseng saponins, and had certain application prospects.

The purpose of this systematic review and meta-analysis was to explore the effects of different soccer practices on fundamental movement skills (FMS) of children of different ages and genders, in order to help children to improve their fundamental movement skills through soccer practice more effectively. The databases of CNKI, Wanfang database, Pubmed, Web of science and Cochrane library were searched to collect relevant studies on the effects of soccer practices on FMS, and the quality of the included studies was evaluated by using the Cochrane Risk of Bias Tool, and Meta-analysis was conducted by Review Manager 5.4 software. 16 studies were finally included, with a total of 3,121 subjects were included. The results showed that soccer had a positive effect on linear sprint ability [SMD 95% CI = −0.37 (−0.61, −0.14), P = 0.002], horizontal jump [SMD 95% CI = 0.22 (−0.34, 0.77), P = 0.003], object control [SMD 95% CI = 1.32 (0.8, 1.85), P = 0.0003], Closed-eye single-leg test [SMD 95% CI = 0.87(0.48,1.25), P