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Abstract Background Ductal carcinoma in situ (DCIS) of the breast is an early stage of breast cancer, and preventing its progression to invasive ductal carcinoma (IDC) is crucial for the early detection and treatment of breast cancer. Although single-cell transcriptome analysis technology has been widely used in breast cancer research, the biological mechanisms underlying the transition from DCIS to IDC remain poorly understood. Results We identified eight cell types through cell annotation, finding significant differences in T cell proportions between DCIS and IDC. Using this as a basis, we performed pseudotime analysis on T cell subpopulations, revealing that differentially expressed genes primarily regulate immune cell migration and modulation. By intersecting WGCNA results of T cells highly correlated with the subtypes and the differentially expressed genes, we identified six key genes: FGFBP2, GNLY, KLRD1, TYROBP, PRF1, and NKG7. Excluding PRF1, the other five genes were significantly associated with overall survival in breast cancer, highlighting their potential as prognostic biomarkers. Conclusions We identified immune cells that may play a role in the progression from DCIS to IDC and uncovered five key genes that can serve as prognostic markers for breast cancer. These findings provide insights into the mechanisms underlying the transition from DCIS to IDC, offering valuable perspectives for future research. Additionally, our results contribute to a better understanding of the biological processes involved in breast cancer progression.

Abstract Endothelial cells are a heterogeneous population with various organ-specific and conserved functions that are critical to organ development, function, and regeneration. Here we report a Sox17-Erg direct reprogramming approach that uses cardiac fibroblasts to create differentiated endothelial cells that demonstrate endothelial-like molecular and physiological functions in vitro and in vivo. Injection of these induced endothelial cells into myocardial infarct sites after injury results in improved vascular perfusion of the scar region. Furthermore, we use genomic analyses to illustrate that Sox17-Erg reprogramming instructs cardiac fibroblasts toward an arterial-like identity. This results in a more efficient direct conversion of fibroblasts into endothelial-like cells when compared to traditional Etv2-based reprogramming. Overall, this Sox17-Erg direct reprogramming strategy offers a robust tool to generate endothelial cells both in vitro and in vivo, and has the potential to be used in repairing injured tissue.

Background As an important global agricultural cash crop, melon has a long history of cultivation and a wide planting area. The physiological metabolism of melon after harvest is relatively strong; if not properly stored, melon is easily invaded by external pathogens during transportation, resulting in economic losses and greatly limiting its production, development and market supply. Therefore, the storage and freshness of melon are the main challenges in realizing the annual supply of melon, so postharvest storage has received increasing amounts of attention from researchers. Methods This study used academic, PubMed, and Web of Science resources to retrieve keywords related to postharvest storage and melon quality; read, refined, classified, and sorted the retrieved literature; sorted and summarized the relevant research results; and finally completed this article. Results This article reviews the mechanism and effects of physical, chemical and biological preservation techniques on the sensory quality, compound contents and respiratory physiological activities of different varieties of melon fruits. When maintaining normal metabolism and not producing physiological disorders, melon inhibits cell wall metabolism, reactive oxygen species metabolism and the ethylene biosynthesis pathway, etc., to the greatest extent during postharvest storage, thereby reducing the material consumption of fruits, delaying the ripening and senescence process, and prolonging the postharvest life and shelf life. Conclusion The literature provides a theoretical basis for postharvest preservation technology in the melon industry in the future and provides corresponding guidance for the development of the melon industry.

Fire detection is crucial due to the exorbitant annual toll on both human lives and the economy resulting from fire-related incidents. To enhance forest fire detection in complex environments, we propose a new algorithm called FD-Net for various environments. Firstly, to improve detection performance, we introduce a Fire Attention (FA) mechanism that utilizes the position information from feature maps. Secondly, to prevent geometric distortion during image cropping, we propose a Three-Scale Pooling (TSP) module. Lastly, we fine-tune the YOLOv5 network and incorporate a new Fire Fusion (FF) module to enhance the network’s precision in identifying fire targets. Through qualitative and quantitative comparisons, we found that FD-Net outperforms current state-of-the-art algorithms in performance on both fire and fire-and-smoke datasets. This further demonstrates FD-Net’s effectiveness for application in fire detection.

The ongoing evolution of SARS-CoV-2 is a significant concern, especially with the decrease in clinical sequencing efforts, which impedes the ability of public health sectors to prepare for the emergence of new variants and potential COVID-19 outbreaks. Wastewater-based epidemiology (WBE) has been proposed as a surveillance program to detect and monitor the SARS-CoV-2 variants being transmitted in communities. However, research is limited in evaluating the effectiveness of wastewater collection at sentinel sites for monitoring disease prevalence and variant dynamics, especially in terms of inferring the epidemic patterns on a broader scale, such as at the state/province level. This study utilized a multiplexed tiling amplicon-based sequencing (ATOPlex) to track the longitudinal dynamics of variant of concern (VOC) in wastewater collected from municipalities in Queensland, Australia, spanning from 2020 to 2022. We demonstrated that wastewater epidemiology measured by ATOPlex exhibited a strong and consistent correlation with the number of daily confirmed cases. The VOC dynamics observed in wastewater closely aligned with the dynamic profile reported by clinical sequencing. Wastewater sequencing has the potential to provide early warning information for emerging variants. These findings suggest that WBE at sentinel sites, coupled with sensitive sequencing methods, provides a reliable and long-term disease surveillance strategy.

Abstract Immunotherapy targeting PD‐L1 is still ineffective for a wide variety of tumors with high unpredictability. Deploying combined immunotherapy with alternative targeting is practical to overcome this therapeutic resistance. Here, the deficiency of serine‐threonine kinase STK24 is observed in tumor cells causing substantial attenuation of tumor growth in murine syngeneic models, a process relying on cytotoxic CD8+ T and NK cells. Mechanistically, STK24 in tumor cells associates with and directly phosphorylates AKT at Thr21, which promotes AKT activation and subsequent PD‐L1 induction. Deletion or inhibition of STK24, by contrast, blocks IFN‐γ‐mediated PD‐L1 expression. Various murine models indicate that in vivo silencing of STK24 can significantly enhance the efficacy of the anti‐PD‐1 blockade strategy. Elevated STK24 levels are observed in patient specimens in multiple tumor types and inversely correlated with intratumoral infiltration of cytotoxic CD8+ T cells and with patient survival. The study collectively identifies STK24 as a critical modulator of antitumor immunity, which engages in AKT and PD‐L1/PD‐1 signaling and is a promising target for combined immunotherapy.

Based on introducing the technical characteristics of FY-3G, which is China's first precipitation measurement satellite and successfully launched at 09∶36 BT on April 16 in 2023, this paper focuses on the precipitation detection capabilities and application prospect in rainstorm monitoring of FY-3G. The results show that, with an orbit at 407 km and an inclination angle of 50°, and equipped with a dual-frequency Ka/Ku band precipitation measurement radar, microwave, and optical imaging instruments, the FY-3G satellite can detect the three-dimensional structure of disastrous weather systems such as typhoon, heavy rainfall, and other strong convection events in most of China. At the design level, FY-3G has precipitation detection capabilities comparable to the current US Second Generation Global Precipitation Measurement Program (GPM) Core Satellite (GPMCO), but better payload types, quantities, and channel settings compared with the GPMCO satellite. After the service operation, the FY-3G satellite, together with other polar-orbiting meteorological satellites such as FY-3 AM, PM, and EM, as well as high-orbit geostationary satellites, will form the Fengyun precipitation detection constellation system, which will improve the overall precipitation detection capability of the Fengyun Satellite constellation and provide stronger basic support for meteorological disaster prevention and mitigation.

With rising global temperatures, wildfires frequently occur worldwide during the summer season. The timely detection of these fires, based on unmanned aerial vehicle (UAV) images, can significantly reduce the damage they cause. Existing Convolutional Neural Network (CNN)-based fire detection methods usually use multiple convolutional layers to enhance the receptive fields, but this compromises real-time performance. This paper proposes a novel real-time semantic segmentation network called FireFormer, combining the strengths of CNNs and Transformers to detect fires. An agile ResNet18 as the encoding component tailored to fulfill the efficient fire segmentation is adopted here, and a Forest Fire Transformer Block (FFTB) rooted in the Transformer architecture is proposed as the decoding mechanism. Additionally, to accurately detect and segment small fire spots, we have developed a novel Feature Refinement Network (FRN) to enhance fire segmentation accuracy. The experimental results demonstrate that our proposed FireFormer achieves state-of-the-art performance on the publicly available forest fire dataset FLAME—specifically, with an impressive 73.13% IoU and 84.48% F1 Score.

Abstract Background Albumin infusion is the primary therapeutic strategy for septic patients with liver cirrhosis. Although recent studies have investigated the efficacy of albumin in the resuscitation stage of septic patients with liver cirrhosis, it remains unclear whether daily albumin administration can improve outcomes. Furthermore, the indications for initiating albumin therapy are not well defined. Methods Septic patients with liver cirrhosis were obtained from the Medical Information Mart for Intensive Care (MIMIC-IV 2.0) database. Marginal structural Cox models were employed to investigate the association between daily albumin infusion and 28-day mortality. We also aimed to explore under what circumstances enrolled patients could benefit most from albumin administration, based on the clinical parameters collected on the day of albumin infusion, including serum albumin concentration, serum lactate concentration, mean arterial pressure (MAP), and vasopressor dosage. Results A total of 2265 patients were included in the final analysis, of whom 1093 (48.3%) had received albumin treatment at least once. The overall 28-day mortality was 29.6%. After marginal structural modeling, daily albumin infusion was associated with a reduced risk of 28-day death (hazard ratio, 0.76; 95% CI 0.61–0.94). We found that patients benefit most from albumin infusion when initiated on the day of serum albumin concentration between 2.5 and 3.0 g/dL, serum lactate concentration greater than or equal to 2 mmol/L, MAP less than 60 mmHg, or vasopressor dosage between 0.2 and 0.3 mcg/kg/min (norepinephrine equivalent, NEE). Conclusions Albumin infusion is associated with a reduction in mortality in septic patients with liver cirrhosis under specific circumstances. Serum albumin concentration, serum lactate, MAP, and vasopressor dosage were found to be modifiers of treatment effectiveness and should be considered when deciding to initial albumin infusion.

The deterioration of soil and water resources resulting from tropical rainforest (TR) conversion to monoculture plantations (e.g., rubber monoculture; RM) could be restrained and restored through intercropping. However, the response of soil properties and forest water conservation function to forest conversion, i.e., the conversion of RM to rubber rainforest (RR: derived from the invasion of wild native plants in abandoned RM), is still unclear. We involved four forests types, TR, RM, rubber-tea agroforestry (RTA), and RR, as transitional steps of forest conversion through a space-for-time substitution approach to examine the dynamic of soil physical, hydrological and chemical properties during the forest conversion (from TR to RM, RM to RTA, RTA to RR, and retransformation into TR). The results show that SOC, TN, TP, and TK decreased in the order of TR > RR > RTA > RM, which was followed by the trend of soil hydrological and physical properties among these forest types. The interrelation between soil physical and chemical properties was mediated by water flow behaviours. High macroporosity and related low Ks in TR favoured the occurrence of water flow behaviours. Water flow behaviours not only influenced the distribution of soil chemical elements but also played a crucial role in forming appropriate conditions for nutrient turnover. The co-occurrence of preferential and matrix flow was more prevalent in the rainy season than dry season due to the higher frequency and higher amount of rainwater. The preferential flow promoted the soil water flow in the water flow paths and enhanced water storage in the soil pores. In short, the soil properties and soil water supply decreased in the following order: TR > RR > RTA > RM, suggesting that the severe soil degradation that occurred after TR conversion to RM can be restored back to the extent of TR after a period of succession. The results provided new insights for understanding the forest water conservation function and soil properties in response to forest conversion and highlighted that the RR appeared as a transitional stage during the course of forest restoration from RM to TR under low rubber demand. These findings improve the current knowledge of the relationship among soil physical, hydrological and chemical properties in the rubber-growing humid tropical region of Southeast Asia.

Abstract Objectives To predict CTLA4 expression levels and prognosis of clear cell renal cell carcinoma (ccRCC) by constructing a computed tomography‐based radiomics model and establishing a nomogram using clinicopathologic factors. Methods The clinicopathologic parameters and genomic data were extracted from 493 ccRCC cases of the Cancer Genome Atlas (TCGA)‐KIRC database. Univariate and multivariate Cox regression and Kaplan–Meier analysis were performed for prognosis analysis. Cibersortx was applied to evaluate the immune cell composition. Radiomic features were extracted from the TCGA/the Cancer Imaging Archive (TCIA) (n = 102) datasets. The support vector machine (SVM) was employed to establish the radiomics signature for predicting CTLA4 expression. Receiver operating characteristic curve (ROC), decision curve analysis (DCA), and precision‐recall curve were utilized to assess the predictive performance of the radiomics signature. Correlations between radiomics score (RS) and selected features were also evaluated. An RS‐based nomogram was constructed to predict prognosis. Results CTLA4 was significantly overexpressed in ccRCC tissues and was related to lower overall survival. A higher CTLA4 expression was independently linked to the poor prognosis (HR = 1.458, 95% CI 1.13–1.881, p = 0.004). The radiomics model for the prediction of CTLA4 expression levels (AUC = 0.769 in the training set, AUC = 0.724 in the validation set) was established using seven radiomic features. A significant elevation in infiltrating M2 macrophages was observed in the RS high group (p

Soil erosion by water is known to be a major driver of land degradation. Splash erosion is the initial stage of water erosion and directly contributes to the detachment of soil particles on sloping land. Splash erosion may be exacerbated or mitigated by ongoing land use/cover change. To estimate the effects of various land use and management systems on splash erosion in the humid tropics, we measured the actual splash erosion under natural rainfall conditions in a tropical rainforest (TR), rubber monoculture (RM), and four rubber agroforestry ecosystems in Xishuangbanna, Southwestern China. The average cumulative splash mass in the RM was 48.7 times higher compared to that in the TR, indicating that the replacement of TR by RM results in severe splash erosion. In the rubber agroforestry systems, the throughfall kinetic energy and splash mass were 34–76% and 86–97% lower, respectively, than that in the RM, indicating that intercropping crops with rubber trees can effectively alleviate erosive power of throughfall and thus splash erosion. Under all land use regimes, in the plots where the litter layer was removed, splash erosion was significantly (2.0–12.1 times) higher and more spatially heterogeneous than in those with litter cover. This highlighted the key role of the forest litter layer in protecting the soil from raindrop detachment. In the study area, the actual splash erosion was strongly correlated with the conditions of precipitation (amount and intensity (I10) of rainfall) and the vegetation structure (especially the crown base height, leaf area index, and canopy cover), but weakly correlated with the soil properties. Given the importance of near-ground intercrops (height

Summary: Direct cardiac reprogramming refers to the conversion of fibroblasts into cardiomyocyte-like cells (iCMs) without going through an intermediate progenitor stage. Here, we present a protocol for direct cardiac reprogramming in mice using Ascl1 and Mef2c. We describe steps for isolating primary neonatal mouse cardiac fibroblast, preparing retrovirus encoding reprogramming factors, and efficient cardiac reprogramming with Ascl1 and Mef2c. The resulting iCMs display cardiomyocyte-like sarcomere structure, gene expression, and calcium flux.For complete details on the use and execution of this protocol, please refer to Wang et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Precipitation is one of the most important parameters in Earth system but is hard to measure. China began to develop satellites dedicated to precipitation measurements in the second generation of the FengYun polar-orbiting meteorological satellite program (FY-3). The first of total 2 rainfall missions scheduled, FY-3G, was successfully launched on 16 April 2023 and became the world’s third satellite to measure precipitation with space-borne radar after the tropical rainfall measuring mission in 1997 and global precipitation measurement core observatory in 2014. In this manuscript, we illustrate the platform of FY-3G and instruments mounted in great detail, with additional information about ground segments, designed sensor-based products, and retrieval of geophysical parameters. During the 4 months after launch, the specifications of the platform and instruments are under inspection as calibration and validation are carefully conducted. The first images captured by FY-3G are encouraging, and initial results show a strong capability for providing insights into all kinds of precipitation phenomena. The important work of data processing, such as data assimilation, data fusion between space-based and ground-based radar, and that between polar and geostationary satellites, as well as future applications in weather modification, has been prepared in advance. As a pioneer of China’s rainfall missions, FY-3G greatly improves our ability to provide global precipitation measurements, understand Earth’s water and energy cycle, and forecast extreme events for the benefit of society.

Glioma is a highly common pathological brain tumor. Misfolded protein response, which is strongly associated with the growth of cancerous tumors, is mediated by the gene, endoplasmic reticulum degradation-enhancing alpha-mannosidase-like protein 2. However, this gene has not been linked to glioma. To assess the same, we used The Cancer Genome Atlas, Chinese Glioma Genome Atlas, and Genotype-Tissue Expression datasets. The gene was overexpressed in gliomas. This overexpression was linked to unfavorable clinical characteristics, such as the World Health Organization grade, isocitrate dehydrogenase mutation, and the combined loss of the short arm chromosome 1 and the long arm of chromosome 19. Quantitative polymerase chain reaction experiments and immunohistochemistry on clinical samples from our institution verified the gene’s expression and clinical importance. The Human Protein Atlas website verified the messenger ribonucleic acid expression of the gene in glioma cell lines, and immunohistochemistry verified the presence of its protein. A previous survival study indicated that its high expression is substantially related to a bad prognosis. It was identified as an independent predictor of primary glioma prognosis using multivariate Cox regression analysis. To forecast individual survival, we created a nomogram based on this (concordance-index = 0.847). Additionally, functional annotation demonstrated its major role in the control of the extracellular matrix and immune system. The scratch assay and transwell migration assay confirmed the decreased invasive ability of U251 glioma cells with the gene knockdown. Its increased expression was found to be related to the extent of macrophage infiltration using the CIBERSORT, ESTIMATE, Single-sample Gene Set Enrichment Analysis, and Tumor Immune Single-Cell Hub (TISCH) algorithms. The Tumor Immune Dysfunction and Exclusion algorithm revealed that the gene can accurately predict the response of immunotherapy (area under the receiver operating characteristic curve = 0.857). Further, isocitrate dehydrogenase 1 mutation is typically more frequent when the gene expression is high. Finally, five medicines targeting this gene were discovered utilizing the molecular docking program and drug sensitivity analysis of the RNAactDrug website. Low expression of the gene inhibited glioma cell invasion. Therefore, the gene is helpful for the diagnosis, prognosis, and case-specific immunotherapy of glioma.

The emergence of the convolutional neural network greatly improves the accuracy of human action recognition. However, with the deepening of the network, fewer and fewer features are extracted, and in some datasets, due to the shooting angle, the size of the target to be recognized is different. To solve this problem, on the basis of resnext human action recognition method, we propose an improved resnext human action recognition method based on multi-feature map fusion. First, the video is uniformly sampled to generate training samples, and we generate samples with different frames as the input to the network. Second, we add n layers of up-sampling layers after layer 1 of resnext, to enlarge the feature maps and extract multiple feature maps, so that the extracted feature maps are clearer, and small targets can be better recognized. Finally, for the n results obtained, we use the weighted geometric means combination forecasting method based on L_1 norm to fuse and obtain the final result. In the process of experiment, using UCF-101 and HMDB-51 for verification, the accuracy of our model is 90.3% on UCF-101, which is higher than most of the state-of-art algorithms.

Plant litter decomposition is a complex, long-term process. The decomposition of litterfall is a major process influencing nutrient balance in forest soil. The soil microbiome is exceptionally diverse and is an essential regulator of litter decomposition. However, the microbiome composition and the interaction with litterfall and soil remain poorly understood. In this study, we examined the bacterial and fungal community composition of Lithocarpus across soil samples from different sampling seasons. Our results displayed that the microbiome assembly along the soil layer is influenced predominantly by the soil layer rather than by the sampling season. We identified that the soil layer strongly affected network complexity and that bacterial and fungal microbiomes displayed different patterns in different soil layers. Furthermore, source tracking and community composition analysis indicated that there are significantly different between soil and litter. Moreover, our results demonstrate that few dominant taxa (2% and 4% of bacterial and fungal phylotypes) dominated in the different soil layers. Hydnodontaceae was identified as the most important biomarker taxa for humic fragmented litter fungal microbiome and Nigrospora and Archaeorhizomycetaceae for organic soil and the organic mineral soil layer, and the phylum of Acidobacteria for the bacteria microbiome. Our work provides comprehensive evidence of significant microbiome differences between soil layers and has important implications for further studying soil microbiome ecosystem functions.

Accurate measurement of the radiative properties of clouds and aerosols is of great significance to global climate change and numerical weather prediction. The multi-angle polarization imager (MAPI) onboard the Fengyun-3 precipitation satellite, planned to be launched in 2023, will provide the multi-angle, multi-shortwave infrared (SWIR) channels and multi-polarization satellite observation of clouds and aerosols. MAPI operates in a non-sun-synchronized inclined orbit and provides images with a spatial resolution of 3 km (sub-satellite) and a swath of 700 km. The observation channels of the MAPI include 1030 nm, 1370 nm, and 1640 nm polarization channels and corresponding non-polarization channels, which provide observation information from 14 angles. In-flight radiometric and polarimetric calibration strategies are introduced, aiming to achieve radiometric accuracy of 5% and polarimetric accuracy of 2%. Simulation experiments show that the MAPI has some unique advantages of characterizing clouds and aerosols. For cloud observation, the polarization phase functions of the 1030 nm and 1640 nm around the scattering angle of a cloudbow show strong sensitivity to cloud droplet radius and effective variance. In addition, the polarized observation of the 1030 nm and 1640 nm has a higher content of information for aerosol than VIS-NIR. Additionally, the unique observation geometry of non-sun-synchronous orbits can provide more radiometric and polarization information with expanded scattering angles. Thus, the multi-angle polarization measurement of the new SWIR channel onboard Fengyun-3 can optimize cloud phase state identification and cloud microphysical parameter inversion, as well as the retrieval of aerosols. The results obtained from the simulations will provide support for the design of the next generation of polarized imagers of China.

Glioma peritumoral brain edema (GPTBE) is a frequent complication in patients with glioma. The severity of peritumoral edema endangers patients’ life and prognosis. However, there are still questions concerning the process of GPTBE formation and evolution. In this study, the patients were split into two groups based on edema scoring findings in the cancer imaging archive (TCIA) comprising 186 TCGA-LGG patients. Using mRNA sequencing data, differential gene (DEG) expression analysis was performed, comparing the two groups to find the key genes affecting GPTBE. A functional enrichment analysis of differentially expressed genes was performed. Then, a protein–protein interaction (PPI) network was established, and important genes were screened. Gene set variation analysis (GSVA) scores were calculated for major gene sets and comparatively correlated with immune cell infiltration. Overall survival (OS) was analyzed using the Kaplan–Meier curve. A total of 59 DEGs were found, with 10 of them appearing as important genes. DEGs were shown to be closely linked to inflammatory reactions. According to the network score, IL10 was in the middle of the network. The presence of the IL10 protein in glioma tissues was verified using the human protein atlas (HPA). Furthermore, the gene sets’ GSVA scores were favorably linked with immune infiltration, particularly, with macrophages. The high-edema group had higher GSVA scores than the low-edema group. Finally, Kaplan–Meier analysis revealed no differences in OS between the two groups, and eight genes were found to be related to prognosis, whereas two genes were not. GPTBE is linked to the expression of inflammatory genes.

Under the comprehensive reform of its household registration system, China has experienced the largest and fastest urbanization process in the world since its establishment 70 years ago, but with the deepening of urbanization, cities are facing greater environmental challenges. As the total amount of urban wastewater discharge increases, the condition of water pollution nationwide has become more severe. Thus, through the use of dynamic exogenous variable data envelopment analysis (DEA) this research selects the employment population and input cost of wastewater treatment in 31 provinces of China from 2013 to 2017 as input indicators, gross domestic product (GDP), wastewater production, and chemical oxygen demand (COD) in wastewater as output indicators, fixed assets as a carry-over variable, and urbanization level as an important influencing factor to evaluate and compare wastewater treatment efficiency in the northeast, central, western, and eastern regions with and without the influence of the level of urbanization. Findings show that the total efficiency score under the influence of the level of urbanization is generally higher than that without such an influence. The level of urbanization has a significantly positive effect on wastewater output efficiency in various regions, whereas wastewater output efficiency presents a downward trend from 2013 to 2017. The overall level of chemical oxygen demand efficiency is weak. When affected by the level of urbanization, the scores of COD efficiency in the eastern, northeast, and central regions have increased significantly. Finally, there is a large inter-provincial gap in the level of urbanization in the western region, while the level of urbanization has no significant impact on COD efficiency.

Abstract Aberrant epigenetic reprogramming represents a hallmark of renal cell carcinoma (RCC) tumorigenesis and progression. Whether there existed other epigenetic vulnerabilities that could serve as therapeutic targets remained unclear and promising. Here, we combined the clustered regularly interspaced short palindromic repeats functional screening results and multiple RCC datasets to identify JMJD6 as the potent target in RCC. JMJD6 expression correlated with poor survival outcomes of RCC patients and promoted RCC progression in vitro and in vivo. Mechanistically, aberrant p300 led to high JMJD6 expression, which activated a series of oncogenic crosstalk. Particularly, high‐throughput sequencing data revealed that JMJD6 could assemble super‐enhancers to drive a list of identity genes in kidney cancer, including VEGFA, β‐catenin, and SRC. Moreover, this JMJD6‐mediated oncogenic effect could be suppressed by a novel JMJD6 inhibitor (SKLB325), which was further demonstrated in RCC cells, patient‐derived organoid models, and in vivo. Given the probable overlapped crosstalk between JMJD6 signature and tyrosine kinase inhibitors downstream targets, targeting JMJD6 sensitized RCC to sunitinib and was synergistic when they were combined together. Collectively, this study indicated that targeting JMJD6 was an effective approach to treat RCC patients.

Background. The aim of this study was to identify novel biomarkers associated with esophageal squamous cell carcinoma (ESCC) prognosis. Methods. 81 ESCC samples collected from The Cancer Genome Atlas (TCGA) were used as the training set, and 179 ESCC samples collected from the Gene Expression Omnibus database (GEO) were used as the validation set. The protein-coding genes of 25 samples from patients who completed the follow-up in TCGA were analyzed to construct a coexpression network by weighted gene coexpression network analysis (WGCNA). Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analyses were performed for the selected genes. The least absolute shrinkage and selection operator (LASSO) Cox regression model was constructed to analyze survival-related genes, and an optimal prognostic model was developed as well as evaluated by Kaplan–Meier and ROC curves. Results. In this study, a module containing 43 protein-coding genes and strongly related to overall survival (OS) was identified through WGCNA. These genes were significantly enriched in retina homeostasis, antimicrobial humoral response, and epithelial cell differentiation. Besides, through the LASSO regression model, 3 genes (PDLIM2, DNASE1L3, and KRT81) significantly related to ESCC survival were screened and an optimal prognostic 3-gene risk prediction model was constructed. ESCC patients with low and high OS in both sets could be successfully discriminated by calculating a risk score with the linear combination of the expression level of each gene multiplied by the LASSO coefficient. Conclusions. Our study identified three novel biomarkers that have potential in the prognosis prediction of ESCC.

The regulation of the autonomic nervous system (ANS) can improve cognitive function in major depressive disorders (MDD). Heart rate variability (HRV) derives from the dynamic control of the ANS and reflects the balance between the activities of the sympathetic and parasympathetic nervous systems by measuring tiny changes in adjacent heart beats. Task-related HRV may reflect the association between the flexibility of cognition and ANS function. The study was to investigate the neural mechanism of interactions between ANS and cognitive function in MDD with Magnetoencephalography (MEG) measurements. Participants included 20 MDD patients and 18 healthy controls (HCs). All participants were measured with a go/no-go task MEG. HRV indices, the standard deviation of the average normal-to-normal (NN) interval calculated over short periods (SDANN) and the square root of the mean squared differences of successive NN intervals (RMSSD), were derived from the raw MEG data. Results showed that MDD patients showed decreased SDANN and RMSSD. In MDD patients, both resting-state and task-related RMSSD were related to inhibitory and control dysfunction. In the go/no-go task, many areas in the prefrontal cortex (PFC) are responsible for an individual’s inhibitory function. A brain MEG functional connectivity analysis revealed that there were significant differences in four brain regions within the prefrontal cortex (PFC) between MDD patients and HCs. Task-related RMSSD in HCs were related to the functional connectivity between the left middle frontal gyrus and the anterior cingulate cortex (ACC), while in MDD patients, these values were not related to the above functional connectivity but were related to the functional connectivity between the left middle frontal gyrus and insula. However, the resting-state RMSSD value was not related to these significant difference functional connectivity networks in all participants. It concludes that the decreased task-related HRV is associated with inhibitory dysfunction through functional inter-region connectivity in the PFC in MDD, and the task-related HRV can be used as an index of the association between MDD and autonomic dysregulation.

Abstract Background Functional dyspepsia (FD) is considered a bio-psychosocial disorder. The role of psychosocial factors in FD pathogenesis remains unclear. Methods This study evaluated sleep quality and mood symptoms in patients with FD, assessing the associations of FD severity, disordered sleep, and psychological symptoms. One-hundred-and-fifteen adult patients with typical FD symptoms were enrolled alongside 61 healthy volunteers. Rome III criteria were used to evaluate FD symptoms; sleep disorder was assessed with the Pittsburgh Sleep Quality Index (PSQI), and Symptom Checklist-90-Revised (SCL-90R) was utilized to determine the status of depression, anxiety and other psychological symptoms. Results PSQI scores and nine symptomatic dimensions of SCL-90R were significantly higher in FD patients than in controls. Multiple logistic regression indicated that lower BMI, lower level of education, and sleep disturbance were independently associated with FD and FD subgroups. Hostility and phobic anxiety were independent risk factors for FD. Further analysis showed that hostility was an independent risk factor for both FD subgroups, and somatization and additional psychiatric symptoms for epigastric pain syndrome. Conclusions We found that FD was associated with sleep disorder and psychopathological factors. These findings suggest that implementing sleeping and/or psychological therapies may help reduce FD symptoms.

Abstract Background ATP-binding cassette sub-family G member 2 (ABCG2) is a semi-transport protein that plays a major role in multidrug resistance. We aimed to evaluate the prognostic significance of ABCG2 expression in patients with clear cell renal cell carcinoma. Methods From 2008 to 2013, 120 patients with clear cell kidney cancer underwent surgery with paraffin-embedded specimens and necessary clinical information available. Immunohistochemistry staining was performed to grade the expression of ABCG2 as ABCG2(−): less than 10% of tumor cells stained; ABCG2(+): weak membrane staining; and ABCG2(++): moderate or strong membrane staining. The overall survival was analyzed using Kaplan-Meier method. Multivariable Cox regression evaluated the independent predictors for overall survival. Results ABCG2(−) was diagnosed in 57 (48%) patients, ABCG2(+) in 52 (43%) patients, and ABCG2 (++) in 11(9.2%) patients. ABCG2 expression significantly correlated with the five-year survival (p

Purpose: We aim to investigate the current esophageal cancer staging according to the 7th edition TNM classification for esophageal carcinoma proposed by American Joint Committee on Cancer (AJCC) among oncology-related physicians in China.Methods: A specifically-designed 14-item questionnaire was distributed to 366 doctors who were working with esophageal cancer patients. We collected and analyzed the feedbacks and explored the possible associations within different departments, including thoracic surgery, the internal medicine of gastroenterology, oncology, and/ radiotherapy in eight different hospitals from central and southern China.Results: Among all the responses, 31.42% of them were from thoracic surgery department, 40.44% were from oncology and/or radiation therapy and 28.14% were from the internal medicine of gastroenterology, respectively. Surprisingly, in total 66.12% of all the physicians were unaware that the 7th edition of esophageal carcinoma TNM classification was released in 2009; only 21.86 and 16.67% of physicians recognized cervical nodes and celiac nodes as regional lymph nodes. Furthermore, 67.21% physicians didn't know that tumor location, histologic grade, and histopathology were accepted as new prognostic factors in the latest TNM system; and 51.37% physicians could not determine the correct TNM classification of esophagogastric junction cancers. Intriguingly, over 50% of them could still design appropriate perioperative strategies.Conclusions: The 7th edition of the TNM classification for esophageal carcinoma is poorly recognized and understood in central and southern China, which might contribute to the relatively low rates of appropriate perioperative procedures applied for esophageal cancer patients.

Mismatched filter is an important technique to suppress the sidelobes of phase-coded pulses. Here, the authors propose a mainlobe windowing procedure, by which a much lower sidelobe level can be obtained at a slightly signal-to-noise ratio loss. Based on this idea, they present two mismatched filter design procedures, namely an integrated sidelobe level (ISL) optimal filter and a peak sidelobe level (PSL) optimal filter. The ISL optimal filter can be obtained by a formula in closed form and the PSL optimal filter can be obtained by optimisation procedures. Simulation results are presented to verify the theory.

The application of ground-based radar to monitor the terrain displacement has attracted more and more attentions recently. Most of the existing ground-based radars utilise a linear horizontal rail where the antennas move to generate the image of the test site. Here, the authors present a topology of antenna array with which the digital elevation model of the observed scene can also be generated besides the 2-D image. Several field experiments have been carried out to evaluate the performance of authors’ developed ground-based differential interferometry radar (GB-DInR) configured with this multiple-input multiple-output (MIMO) antenna array. The results demonstrate that authors’ developed MIMO GB-DInR is able to achieve a sub-millimetre precision of displacement measurement and derive the elevation information of target with an error of

Innate lymphoid cells (ILCs), defined as a heterogeneous population of lymphocytes, have received much attention over recent years. They can be categorized into three subsets according to the expression profiles of transcription factors and differing levels of cytokine production. These cells are widely distributed in human organs and tissues, especially in mucosal tissue. The ILCs are involved in various physiological and pathological processes, including inflammation, worm expulsion, autoimmune disease and tumor progression, many of which have been investigated and clarified in recent studies. In the tumor microenvironment, group 2 innate lymphoid cells (ILC2s) have been proved to be able to either promote or inhibit tumor progression by producing different cytokines, recruiting diverse types of immune cells, expressing immunosuppressive molecules and by regulating the expression of certain inflammatory factors. This review summarizes recent research progress on the immunomodulatory functions of ILC2s in the tumor microenvironment and puts forward some perspectives for future study.

Epidermal growth factor receptor (EGFR) mutations occur in up to 50% of Asian patients with non-small cell lung cancer (NSCLC). Treatment of advanced NSCLC patients with EGFR-tyrosine kinase inhibitor (EGFR-TKI) confers a significant survival benefit. This study assessed the efficacy and safety of chemotherapy with or without icotinib in patients undergoing resection of stage IB to ⅢA EGFR-mutated NSCLC.Patients with surgically resected stage IB (with high risk factors) to ⅢA EGFR-mutated NSCLC were randomly assigned (1:1) to one of two treatment plans. One group received four cycles of platinum-based doublet chemotherapy every three weeks, and the other group received platinum-based chemotherapy supplemented with consolidation therapy of orally administered icotinib (125 mg thrice daily) two weeks after chemotherapy. The icotinib treatment continued for four to eight months, or until the occurrence of disease relapse, metastasis or unacceptable icotinib or chemotherapy toxicity. The primary endpoint was disease-free survival (DFS).41 patients were enrolled between Feb 9, 2011 and Dec 17, 2012. 21 patients were assigned to the combined chemotherapy plus icotinib treatment group, while 20 patients received chemotherapy only. DFS at 12 months was 100% for icotinib-treated patients and 88.9% for chemotherapy-only patients (p = 0. 122). At 18 months DFS for icotinib-treated vs. chemotherapy-only patients was 95.2% vs. 83.3% (p = 0. 225), respectively, and at 24 months DFS was 90.5% vs. 66.7% (p = 0. 066). The adverse chemotherapy effects predominantly presented as gastrointestinal reactions and marrow suppression, and there was no significant difference between the two treatment groups. Patients in the chemotherapy plus icotinib treatment group showed favorable tolerance to oral icotinib.The results suggest that chemotherapy plus orally icotinib displayed better DFS compared with chemotherapy only, yet the difference in DFS was not significant. We would think the preliminary result here was promising, and further trials with larger sample sizes might confirm the efficiency of adjuvant TKI in selected patients.ClinicalTrials.gov NCT02430974.