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Abstract Stretchable phosphorescence materials potentially enable applications in diverse advanced fields in wearable electronics. However, achieving room-temperature phosphorescence materials simultaneously featuring long-lived emission and good stretchability is challenging because it is hard to balance the rigidity and flexibility in the same polymer. Here we present a multiphase engineering for obtaining stretchable phosphorescent materials by combining stiffness and softness simultaneously in well-designed block copolymers. Due to the microphase separation, copolymers demonstrate an intrinsic stretchability of 712%, maintaining an ultralong phosphorescence lifetime of up to 981.11 ms. This multiphase engineering is generally applicable to a series of binary and ternary initiator systems with color-tunable phosphorescence in the visible range. Moreover, these copolymers enable multi-level volumetric data encryption and stretchable afterglow display. This work provides a fundamental understanding of the nanostructures and material properties for designing stretchable materials and extends the potential of phosphorescence polymers.

Abstract Background Colorectal cancer (CRC) lacks established biomarkers or molecular targets for predicting or enhancing radiation response. Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 2 (PREX2) exhibits intricate implications in tumorigenesis and progression. Nevertheless, the precise role and underlying mechanisms of PREX2 in CRC radioresistance remain unclear. Methods RNA-seq was employed to identify differentially expressed genes between radioresistant CRC cell lines and their parental counterparts. PREX2 expression was scrutinized using Western blotting, real-time PCR, and immunohistochemistry. The radioresistant role of PREX2 was assessed through in vitro colony formation assay, apoptosis assay, comet assay, and in vivo xenograft tumor models. The mechanism of PREX2 was elucidated using RNA-seq and Western blotting. Finally, a PREX2 small-molecule inhibitor, designated PREX-in1, was utilized to enhance the efficacy of ionizing radiation (IR) therapy in CRC mouse models. Results PREX2 emerged as the most significantly upregulated gene in radioresistant CRC cells. It augmented the radioresistant capacity of CRC cells and demonstrated potential as a marker for predicting radioresistance efficacy. Mechanistically, PREX2 facilitated DNA repair by upregulating DNA-PKcs, suppressing radiation-induced immunogenic cell death, and impeding CD8+ T cell infiltration through the cGAS/STING/IFNs pathway. In vivo, the blockade of PREX2 heightened the efficacy of IR therapy. Conclusions PREX2 assumes a pivotal role in CRC radiation resistance by inhibiting the cGAS/STING/IFNs pathway, presenting itself as a potential radioresistant biomarker and therapeutic target for effectively overcoming radioresistance in CRC.

Photoacoustic spectroscopy (PAS) has been rapidly developed and applied to different detection scenarios. The acoustic pressure detection is an important part in the PAS system. In this paper, an ultrahigh sensitivity Fabry-Perot acoustic sensor with a T-shaped cantilever was proposed. To achieve the best acoustic pressure effect, the dimension of the cantilever structure was designed and optimized by finite element analysis using COMSOL Multiphysics. Simulation results showed that the sensitivity of such T-shaped cantilever was 1.5 times higher than that based on a rectangular cantilever, and the resonance frequency of T-shaped cantilever were able to modulate from 800 Hz to 1500 Hz by adjusting the multi-parameter characteristics. Experimental sensing results showed that the resonance frequency of T-shaped Fabry-Perot acoustic sensor was 1080 Hz, yielding a high sensitivity of 1.428 μm/Pa, with a signal-to-noise ratio (SNR) of 84.8 dB and a detectable pressure limit of 1.9 μPa/Hz1/2@1 kHz. We successfully used such acoustic sensor to measure acetylene (C2H2) concentration in the PAS. The sensitivity of PAS for C2H2 gas was 3.22 pm/ppm with a concentration range of 50 ppm ∼100 ppm, and the minimum detection limit was 24.91ppb.

Objective To investigate the differential diagnosis of 1 anti-C, e alloantibodies combined with anti-e, Jkb mimicking alloantibodies by absorption-elution test and titer integral method. Methods ABO, Rh and Kidd blood group antigens were identified by tube method. Two sets of panel cells were used for antibody screening and antibody specificity identification by saline method, polyamine method and microcolumn gel method.The antibody was further confirmed by multiple absorption-elution tests and titer integral method. RHCE and JK gene were sequenced by multiple PCR. Results Serological gene sequencing analysis showed that the ABO blood group of the patient was A type with Rh subtype ccDEE and was positive for direct antiglobulin test (DAT). Multiple absorption-elution tests and titer integral method demonstrated that the serum of the patient contained anti-C, e alloantibodies along with anti-e, Jkb mimicking autoantibodies and there were anti-e, Jkb mimicking autoantibodies on red blood cells(RBCs). According to gene sequencing analysis, there was G>C at exon 676 of the RHCE gene, and the remaining exons were not mutated, suggesting that the RHCE phenotype was ccEE. The 838 G/A heterozygote of exon 9 in JK gene, Jk blood group phenotype was Jk (a+ b+ ). Cross matched type A ccDEE and Jk(a+ b-) RBCs were transfused, and no adverse reactions occurred. Conclusion Serology combined with molecular biology to identify the phenotype of the patient′s RBCs, absorption-elution test and titer integral method to identify the antibody of the patient′s serum can detect the alloantibody type, thus providing strategies for targeted blood transfusion.

Abstract Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

Burned area (BA) plays a pivotal role in fire management and the assessment of fire impact on earth-atmosphere system. Threshold-based segmentation from a single image is an efficient and operational method for detecting BA. However, the great diversity of fire conditions necessitates an adaptive threshold that considers environmental variations. This paper presents a maximum curvature segmentation method to capture the adaptative thresholds. The spectral contrasts in near-infrared (NIR) and shortwave infrared (SWIR) bands were utilized to distinguish BA. The decreased NIR threshold was employed to obtain the burned candidates, and the increased SWIR threshold was then applied to confirm the candidates. Experiments were conducted in different biomes, covering the boreal forest, tropical forest, savanna, and Mediterranean, and different seasons including growing and non-growing seasons. The thresholds changed in each tile, indicating the algorithm adapted the spatial and temporal variations. Comparison with the Burned Area Reference Database was performed at different biomes, resulting in overall dice coefficient (DC), omission error (OE), commission error (CE), and relative Bias (relB) being 0.86, 0.18, 0.10, and −0.08, respectively. The algorithm provides an avenue for adaptive detection of burned areas, and the single-image based approach can provide real-time burned information for wildfire management systems.

ABSTRACTT cell immunity is critical for human defensive immune response. Exploring the key molecules during the process provides new targets for T cell-based immunotherapies. CMC1 is a mitochondrial electron transport chain (ETC) complex IV chaperon protein. By establishing in-vitro cell culture system and Cmc1 gene knock out mice, we evaluated the role of CMC1 in T cell activation and differentiation. The B16-OVA tumor model was used to test the possibility of targeting CMC1 for improving T cell anti-tumor immunity. We identified CMC1 as a positive regulator in CD8+T cells activation and terminal differentiation. Meanwhile, we found that CMC1 increasingly expressed in exhausted T (Tex) cells. Genetic lost of Cmc1 inhibits the development of CD8+T cell exhaustion in mice. Instead, deletion of Cmc1 in T cells prompts cells to differentiate into metabolically and functionally quiescent cells with increased memory-like features and tolerance to cell death upon repetitive or prolonged T cell receptor (TCR) stimulation. Further, the in-vitro mechanistic study revealed that environmental lactate enhances CMC1 expression by inducing USP7, mediated stabilization and de-ubiquitination of CMC1 protein, in which a mechanism we propose here that the lactate-enriched tumor microenvironment (TME) drives CD8+TILs dysfunction through CMC1 regulatory effects on T cells. Taken together, our study unraveled the novel role of CMC1 as a T cell regulator and its possibility to be utilized for anti-tumor immunotherapy.

Postpartum depression (PPD) has a significant impact on the physical and mental health of mothers, potentially leading to symptoms such as low mood, fatigue, and decreased appetite. It may also affect the healthy growth of the infant. The onset of PPD is closely related to abnormalities in inflammation and the immune system. PPD patients exhibit abnormalities in the proportion of peripheral blood immune cells, along with an increase in pro-inflammatory cytokines. Excessive pro-inflammatory cytokines in peripheral blood can disrupt the blood-brain barrier (BBB) by activating astrocytes and reducing transendothelial electrical resistance (TEER), allowing peripheral immune cells or cytokines to enter the brain and trigger inflammation, ultimately leading to the onset of depression. In addition, PPD lacks safe and effective treatment medications. In this study, we collected peripheral blood from both healthy postpartum women and those with PPD, conducted single cell RNA sequencing (scRNA-seq), and used an in-house analytical tool scSTAR to reveal that PPD patients exhibit elevated proportions of peripheral blood cDC2 and Proliferation B cells, which are significantly correlated with IL-1β. Additionally, animal experiments were designed to validate that 919 granules can improve PPD by modulating the levels of peripheral blood IL-1β, providing a potential therapeutic mechanism for PPD treatment.

Abstract Background Prostate cancer (PCA) is the fifth leading cause of cancer-related deaths worldwide, with limited treatment options in the advanced stages. The immunosuppressive tumor microenvironment (TME) of PCA results in lower sensitivity to immunotherapy. Although molecular subtyping is expected to offer important clues for precision treatment of PCA, there is currently a shortage of dependable and effective molecular typing methods available for clinical practice. Therefore, we aim to propose a novel stemness-based classification approach to guide personalized clinical treatments, including immunotherapy. Methods An integrative multi-omics analysis of PCA was performed to evaluate stemness-level heterogeneities. Unsupervised hierarchical clustering was used to classify PCAs based on stemness signature genes. To make stemness-based patient classification more clinically applicable, a stemness subtype predictor was jointly developed by using four PCA datasets and 76 machine learning algorithms. Results We identified stemness signatures of PCA comprising 18 signaling pathways, by which we classified PCA samples into three stemness subtypes via unsupervised hierarchical clustering: low stemness (LS), medium stemness (MS), and high stemness (HS) subtypes. HS patients are sensitive to androgen deprivation therapy, taxanes, and immunotherapy and have the highest stemness, malignancy, tumor mutation load (TMB) levels, worst prognosis, and immunosuppression. LS patients are sensitive to platinum-based chemotherapy but resistant to immunotherapy and have the lowest stemness, malignancy, and TMB levels, best prognosis, and the highest immune infiltration. MS patients represent an intermediate status of stemness, malignancy, and TMB levels with a moderate prognosis. We further demonstrated that these three stemness subtypes are conserved across pan-tumor. Additionally, the 9-gene stemness subtype predictor we developed has a comparable capability to 18 signaling pathways to make tumor diagnosis and to predict tumor recurrence, metastasis, progression, prognosis, and efficacy of different treatments. Conclusions The three stemness subtypes we identified have the potential to be a powerful tool for clinical tumor molecular classification in PCA and pan-cancer, and to guide the selection of immunotherapy or other sensitive treatments for tumor patients.

The discrete time-cost tradeoff problem (DTCTP) is a well-researched topic in the field of operations research. The majority of existing DTCTP models are based on traditional activity networks, which permit the execution of an activity as soon as all its predecessors have been completed. This assumption is reasonable, but it is important to note that there are always exceptions. The main work of this study was threefold. Firstly, we expanded the analysis of the DTCTP to encompass time-constrained activity networks (DTCTPTC), which encompassed three different types of time constraints. The first constraint was the time-window constraint, which limited the time interval during which an activity could be executed. The second constraint was the time-schedule constraint, which specified the times at which an activity could begin execution. The third constraint was the time-switch constraint, which required project activities to start at specific times and remain inactive during designated time periods. Secondly, a constraint programming (CP) model was developed for the purpose of solving the DTCTPTC. The model employed interval variables to define the activity and its potential time constraints, while CP expressions were utilized to ensure the feasibility of the solution. The objective was to identify the optimal execution mode for each activity, the optimal start times for time-scheduled activities, and the optimal work/rest patterns for time-switch activities, with the aim of minimizing the total cost of the project. Finally, the efficacy of the proposed CP model was validated through two case studies based on two illustrative projects of varying sizes. The outcomes were then compared against existing algorithms. The results demonstrated that time constraints were important factors affecting schedule optimization, and the proposed CP model had the ability to solve large-scale DTCTPTC.

A high sensitivity and ultra-low concentration range photoacoustic spectroscopy (PAS) gas detection system, which was based on a novel trapezoid compound ellipsoid resonant photoacoustic cell (TCER-PAC) and partial least square (PLS), was proposed to detect acetylene (C2H2) gas. In the concentration range of 0.5 ppm ∼ 10.0 ppm, the limit of detection (LOD) values of TCER-PAC-based PAS system without data processing was 66.4 ppb, which was lower than that of the traditional trapezoid compound cylindrical resonant photoacoustic cell (TCCR-PAC). The experimental results indicated that the TCER-PAC had higher sensitivity than of TCCR-PAC. Within the concentration range of 12.5 ppb ∼ 125.0 ppb, the LOD and limit of quantification (LOQ) of TCER-PAC-based PAS system combined with PLS regression algorithm were 1.1 ppb and 3.7 ppb, respectively. The results showed that higher detection sensitivity and lower LOD were obtained by PAS system with TCER-PAC and PLS than that of TCCR-PAC-based PAS system.

Abstract Background To explore whether local transplantation of mesenchymal stem cells (MSCs) in temporal muscle can promote collateral angiogenesis and to analyze its main mechanisms of promoting angiogenesis. Methods Bilateral carotid artery stenosis (BCAS) treated mice were administrated with encephalo-myo-synangiosis (EMS), and bone marrow mesenchymal stem cells (BMSCs) were transplanted into the temporal muscle near the cerebral cortex. On the 30th day after EMS, the Morris water maze, immunofluorescence, laser speckle imaging, and light sheet microscopy were performed to evaluate angiogenesis; In addition, rats with bilateral common carotid artery occlusion were also followed by EMS surgery, and BMSCs from GFP reporter rats were transplanted into the temporal muscle to observe the survival time of BMSCs. Then, the concentrated BMSC-derived conditioned medium (BMSC-CM) was used to stimulate HUVECs and BMECs for ki-67 immunocytochemistry, CCK-8, transwell and chick chorioallantoic membrane assays. Finally, the cortical tissue near the temporal muscle was extracted after EMS, and proteome profiler (angiogenesis array) as well as RT-qPCR of mRNA or miRNA was performed. Results The results of the Morris water maze 30 days after BMSC transplantation in BCAS mice during the EMS operation, showed that the cognitive impairment in the BCAS + EMS + BMSC group was alleviated (P

As we face increasing challenges of world food security and malnutrition, coarse cereals are coming into favor as an important supplement to human staple foods due to their high nutritional value. In addition, their functional components, such as flavonoids and polyphenols, make them an important food source for healthy diets. However, we lack a systematic understanding of the importance of coarse cereals for world food security and nutritional goals. This review summarizes the worldwide cultivation and distribution of coarse cereals, indicating that the global area for coarse cereal cultivation is steadily increasing. This paper also focuses on the special adaptive mechanisms of coarse cereals to drought and discusses the strategies to improve coarse cereal crop yields from the perspective of agricultural production systems. The future possibilities, challenges, and opportunities for coarse cereal production are summarized in the face of food security challenges, and new ideas for world coarse cereal production are suggested.

ObjectiveNumerous observational investigations have documented a correlation between asthma and ulcerative colitis(UC). In this Mendelian Randomization (MR) study, we utilized extensive summary data from Genome-Wide Association Studies (GWAS) to further estimate the association between adult-onset asthma and the risk of UC, and to investigate the role of Interleukin-18 (IL-18) as a potential mediator.Materials and methodsA two-step, two-sample MR study was conducted through mediation analysis. For this study, we employed a two-sample MR analysis using the inverse variance-weighted (IVW), weighted median, weighted mode, and MR-Egger regression techniques. We utilized publicly accessible summary statistics from a GWAS meta-analysis of adult-onset asthma in the UK Biobank (n=327,253; cases=26,582; controls=300,671) as the exposure factor. The outcomes were derived from GWAS data of individuals with European ancestry (n=26,405; cases=6,687; controls=19,718). GWAS data for IL-18 were obtained from individuals of European ancestry (n=9,785,222; cases=3,636; controls=9,781,586).ResultsThe MR analysis indicates that adult-onset asthma is associated with an increased risk of UC, with an odds ratio (OR) of 1.019 (95% CI 1.001–1.045, P=0.006). However, there is no strong evidence to suggest that UC significantly impacts the risk of adult-onset asthma. IL-18 may act as a potential mediator in the causal relationship between adult-onset asthma and UC, with a mediation proportion of 3.9% (95% CI, 0.6%–6.9%).ConclusionIn summary, our study established a causal relationship between asthma and UC, in which IL-18 contributes to a small extent. However, the primary factors underlying the influence of asthma on UC remain unclear. Future research should focus on identifying other potential mediators. In clinical practice, it is important to pay greater attention to intestinal lesions in patients with asthma.

Background Haemodynamic instability and hypoxaemia are common and serious threats to the survival of neonates. A growing body of literature indicates that critical care ultrasound has become the optimal evaluation tool for sick neonates. However, few studies have described sonographic characteristics of haemodynamics systematically in the neonates with critical illness. This protocol describes a prospective observational cohort study aimed at (1) characterising the sonographic characteristics of the neonates with critical diseases; and (2) assessing the mortality, significant morbidity, utility of vasoactive medications, fluid resuscitation, duration of ventilation, etc.Methods and analysis This is a single-centre, prospective and observational study conducted in Chengdu Women’s and Children’s Central Hospital from 1 December 2022 to 31 December 2027. Neonates admitted to the neonatal intensive care unit will be recruited. After inclusion, the neonates will undergo the neonatal critical care ultrasound. The data collected via case report forms include clinical variables and sonographic measures. The primary outcome is to identify the sonographic characteristics of sick neonates with different diseases, and the secondary outcome is to describe the mortality, significant morbidity, utility of vasoactive medications, fluid resuscitation and duration of ventilation.Discussion Our study provided an organised neonatal critical care ultrasound workflow, which can be applied in practice. Accordingly, this study will first set up large data on the sonographic description of the neonates with critical illness, which can help to understand the pathophysiology of the critical illness, potentially titrating the treatment.Trial registration number Chinese Clinical Trial Registry (ChiCTR2200065581; https://www.chictr.org.cn/com/25/showproj.aspx?proj=184095).

Summary: A deep understanding of immunotherapy response/resistance mechanisms and a highly reliable therapy response prediction are vital for cancer treatment. Here, we developed scCURE (single-cell RNA sequencing [scRNA-seq] data-based Changed and Unchanged cell Recognition during immunotherapy). Based on Gaussian mixture modeling, Kullback-Leibler (KL) divergence, and mutual nearest-neighbors criteria, scCURE can faithfully discriminate between cells affected or unaffected by immunotherapy intervention. By conducting scCURE analyses in melanoma and breast cancer immunotherapy scRNA-seq data, we found that the baseline profiles of specific CD8+ T and macrophage cells (identified by scCURE) can determine the way in which tumor microenvironment immune cells respond to immunotherapy, e.g., antitumor immunity activation or de-activation; therefore, these cells could be predictive factors for treatment response. In this work, we demonstrated that the immunotherapy-associated cell-cell heterogeneities revealed by scCURE can be utilized to integrate the therapy response mechanism study and prediction model construction. Motivation: Single-cell RNA sequencing (scRNA-seq) has significantly advanced our understanding of how different types of cells respond to immunotherapy. However, inconsistencies persist in our understanding of the mechanistic underpinnings and in predictive models of immunotherapy, with studies reporting different cell subtypes contributing to mechanisms of response and prediction models without clear explanation. Such inconsistencies might originate from uncharacterized cellular heterogeneity. To tackle this issue, we present scCURE, which leverages pattern recognition modeling to differentiate between changed and unchanged cells during the course of immunotherapy.

Abstract Background Heart development protein with EGF‐like domains 1 (HEG1), generally related to angiogenesis and embryonic development, was reported to participate in the occurrence and progression of some tumors recently. However, the role of HEG1 in lung adenocarcinoma (LUAD) is unclear. Patients and Methods To explore the effect of HEG1 on LUAD, GEPIA platform and UALCAN database, as well as Kaplan–Meier plotter were adopted to analyze the association of HEG1 with clinicopathological characteristics and survival outcomes for LUAD firstly. And then the HEG1 in LUAD tissues, blood and cell lines were detected by qRT‐PCR, western blot, immunofluorescence, immunohistochemistry, and ELISA. Gene set enrichment analysis (GSEA) was conducted to identify pathways that might be affected by HEG1 in LUAD. Results In this study, HEG1 in lung tissues and cell lines of LUAD were significantly downregulated compared to benign pulmonary disease tissues and alveolar epithelial cells (p

Abstract Background The risk factors for osteoporosis and its prognostic value in patients with bronchiectasis is not well characterized. We explored the risk factors for osteoporosis and its prognostic impact in hospitalized non-cystic fibrosis bronchiectasis (NCFB) patients in Southeast China. Methods This observational cohort study consecutively enrolled 179 hospitalized patients with NCFB bronchiectasis between 2017 and 2021. The risk factors and the impact of osteoporosis on all-cause mortality were assessed. Results 21.2% (38/179) of hospitalized NCFB patients were diagnosed with osteoporosis. Patients with osteoporosis had more severe symptoms (assessed by chronic airway assessment test, CAT, median 22 vs. 17, P = 0.017), poorer quality of life (assessed by St. George Respiratory Questionnaires, SQRC, median 42 vs. 27, P = 0.007), more severe disease stage (assessed by bronchiectasis severity index, BSI, median 14 vs. 11, P = 0.02), more comorbidities (assessed by Bronchiectasis Aetiology Comorbidity Index, BACI, median 5 vs. 4, P = 0.021) than patients without. Age, female sex, anemia, post-infection, and history of regular inhaled corticosteroid treatment were independent risk factors for osteoporosis in those patients. 21 patients (11.7%) died over a median follow-up period of 32 months. The all-cause mortality in NCFB patients with osteoporosis [28.94% (11/38)] was significantly higher than those without osteoporosis [7.09% (10/141)] [hazard ratio (HR) 5.34, 95% confidence interval (CI) 2.26–12.67, P

Flat panel displays are electronic displays that are thin and lightweight, making them ideal for use in a wide range of applications, from televisions and computer monitors to mobile devices and digital signage. The Thin-Film Transistor (TFT) layer is responsible for controlling the amount of light that passes through each pixel and is located behind the liquid crystal layer, enabling precise image control and high-quality display. As one of the important parameters to evaluate the display performance, the faster response time provides more frames in a second, which benefits many high-end applications, such as applications for playing games and watching movies. To further improve the response time, the single-pixel charging efficiency is investigated in this paper by optimizing the TFT dimensions in gate driver circuits in active-matrix liquid crystal displays. The accurate circuit simulation model is developed to minimize the signal’s fall time (Tf) by optimizing the TFT width-to-length ratio. Our results show that using a driving TFT width of 6790 μm and a reset TFT width of 640 μm resulted in a minimum Tf of 2.6572 μs, corresponding to a maximum pixel charging ratio of 90.61275%. These findings demonstrate the effectiveness of our optimization strategy in enhancing pixel charging efficiency and improving display performance.

BackgroundMost patients with high-grade serous ovarian cancer (HGSOC) experienced disease recurrence with cumulative chemoresistance, leading to treatment failure. However, few biomarkers are currently available in clinical practice that can accurately predict chemotherapy response. The tumor immune microenvironment is critical for cancer development, and its transcriptomic profile may be associated with treatment response and differential outcomes. The aim of this study was to develop a new predictive signature for chemotherapy in patients with HGSOC.MethodsTwo HGSOC single-cell RNA sequencing datasets from patients receiving chemotherapy were reinvestigated. The subtypes of endoplasmic reticulum stress-related XBP1+ B cells, invasive metastasis-related ACTB+ Tregs, and proinflammatory-related macrophage subtypes with good predictive power and associated with chemotherapy response were identified. These results were verified in an independent HGSOC bulk RNA-seq dataset for chemotherapy. Further validation in clinical cohorts used quantitative real-time PCR (qRT-PCR).ResultsBy combining cluster-specific genes for the aforementioned cell subtypes, we constructed a chemotherapy response prediction model containing 43 signature genes that achieved an area under the receiver operator curve (AUC) of 0.97 (p = 2.1e-07) for the GSE156699 cohort (88 samples). A huge improvement was achieved compared to existing prediction models with a maximum AUC of 0.74. In addition, its predictive capability was validated in multiple independent bulk RNA-seq datasets. The qRT-PCR results demonstrate that the expression of the six genes has the highest diagnostic value, consistent with the trend observed in the analysis of public data.ConclusionsThe developed chemotherapy response prediction model can be used as a valuable clinical decision tool to guide chemotherapy in HGSOC patients.

Abstract Renal cell carcinoma (RCC) seriously threatens people's lives and health. The identification of some precise biomarkers during the process of RCC progression and the pathophysiologic procedure is critical for improving the diagnosis and management of RCC. Evidence suggests that ferroptosis may play a pivotal role in eradicating clear cell RCC (ccRCC, KIRC) tumor cells. We screened out the target prognostic ferroptosis‐associated genes and examined the functions of farnesyl‐diphosphate farnesyltransferase (FDFT1) in 786‐O cells by plasmid transfection. In our study, we identified FDFT1 as a potential marker correlating with ferroptosis in KIRC. Upregulated FDFT1 inhibited cell proliferation, migration, and invasion, and the underlying antitumor effects may occur via the AKT signaling pathway. Our study provides helpful evidence to study the complex physiopathology of KIRC.

Despite great success in generation of ultralong organic phosphorescence (UOP) by suppressing non-radiative transitions through attractive interactions, consideration of repulsive interactions on UOP remains largely unexplored. Here, the authors introduce carboxyl groups into organic phosphors, enabling formation of the intense repulsive interactions between the isolated molecules and the matrix in rigid environment.

The authors achieved the X-ray-excited organic phosphorescent scintillation from copolymers through copolymerization of bromine-substituted chromophores and acrylic acid and demonstrated their potential application in X-ray radiography.

BackgroundAnemia leads to a lower cure rate and poor prognosis in tuberculosis patients. Effective predictors for the prognosis of tuberculosis with anemia (A-TB) are urgently needed. Monocyte has been proven to be a prognostic biomarker of many lung diseases. Whether monocyte that the predominant innate immune cell as early defense against tuberculosis can predict A-TB is not known.MethodsData for A-TB patients with initial treatment in Shanghai Pulmonary Hospital were retrospectively collected and analyzed. Logistics regression analysis was used to study the correlation between peripheral blood cells and treatment outcomes. The receiver operating characteristic (ROC) curve was used to determine the cut-off value. We estimated a 12-month prognosis using Kaplan–Meier techniques. The Cox proportional hazards model was used for the univariate and multivariate analyses to analyze the predictors of poor prognosis of A-TB.ResultsOf 181 patients analyzed, 94 were cured and 87 non-cured. Logistic regression analysis identified monocyte as an independent immune-related risk factor for the prognosis of A-TB (OR: 7.881, 95% CI: 1.675–37.075, P = 0.009). The ROC curve analysis proved that the most discriminative cut-off value of monocyte was 0.535 × 10^9/L. K–M analysis demonstrated that the cumulative cure rates of A-TB were significantly higher in A-TB with monocyte < 0.535 × 10^9/L (69.62%) than that in those with monocyte ≥ 0.535 × 10^9/L (38.24%) (Log-rank, χ2 = 16.530, P < 0.0001). On univariate and multivariable analysis, monocyte was an independent predictor of poor prognosis in A-TB. Similarly, monocyte was also an independent predictor of poor pulmonary cavity closure in A-TB (HR: 3.614, 95% CI: 1.335–9.787, P = 0.011).ConclusionIn A-TB patients, elevated monocyte was associated with poor prognosis and poor cavity pulmonary closure. Monocyte may provide a simple and inexpensive prognostic biomarker in A-TB.

BackgroundMyocardial infarction (MI) is a common cardiac condition with a high incidence of morbidity and mortality. Despite extensive medical treatment for MI, the development and outcomes of post-MI heart failure (HF) continue to be major factors contributing to poor post-MI prognosis. Currently, there are few predictors of post-MI heart failure.MethodsIn this study, we re-examined single-cell RNA sequencing and bulk RNA sequencing datasets derived from the peripheral blood samples of patients with myocardial infarction, including patients who developed heart failure and those who did not develop heart failure after myocardial infarction. Using marker genes of the relevant cell subtypes, a signature was generated and validated using relevant bulk datasets and human blood samples.ResultsWe identified a subtype of immune-activated B cells that distinguished post-MI HF patients from non-HF patients. Polymerase chain reaction was used to confirm these findings in independent cohorts. By combining the specific marker genes of B cell subtypes, we developed a prediction model of 13 markers that can predict the risk of HF in patients after myocardial infarction, providing new ideas and tools for clinical diagnosis and treatment.ConclusionSub-cluster B cells may play a significant role in post-MI HF. We found that the STING1, HSPB1, CCL5, ACTN1, and ITGB2 genes in patients with post-MI HF showed the same trend of increase as those without post-MI HF.

Renal ischemia is the initial stage of kidney damage, leading to mitochondrial metabolism disorders and cell necrosis. In this study, we aimed to investigate the biological functions and potential mechanisms of miR-21 in protecting renal tubular epithelial cells from oxidative stress and apoptosis following oxygen glucose deprivation (OGD). Following an OGD injury, miR-21 levels increased in HK-2 renal tubular epithelial cells. Overexpression of miR-21 decreased the protein expressions of cleaved caspase-3, BAX, P53, cell apoptosis and increased Bcl-2 expression in HK-2 cells with OGD injury. In vivo studies found that miR-21 agomir reduced renal tissue apoptosis, while miR-21 antagomir increased it. In addition, overexpression of miR-21 reduced levels of reactive oxygen species (ROS), malondialdehyde (MDA) and lactate dehydrogenase (LDH) in HK-2 cells with OGD injury. However, miR-21 inhibition exhibited the opposite effect. A dual-luciferase reporter assay demonstrated that miR-21 directly regulates Toll-like receptor 4 (TLR4) by targeting the 3′-UTR of TLR4 mRNA. Overexpression of miR-21 led to decreased TLR4 protein expression, and TLR4 knockdown was shown to greatly increase AKT activity in HK-2 cells by in vitro kinase assay. Additionally, TLR4 knockdown promoted AKT phosphorylation and hypoxia-inducible factor-1α (HIF-1α) expression, while TLR4 overexpression inhibited these processes. Furthermore, AKT activation abolished the effect of TLR4 on HIF-1α, while AKT inhibition decreased the expression of TLR4 on HIF-1α in TLR4 knockdown HK-2 cells. Further study revealed that HIF-1α inhibition abolished the protective effect of miR-21 overexpression on ROS, LDH levels and cell apoptosis in HK-2 cells after OGD injury, which is indicated by increased levels of ROS and LDH, as well as increased cell apoptosis after HIF-1α inhibition in miR-21-treated HK-2 cells. In conclusion, miR-21 defends OGD-induced HK-2 cell injury via the TLR4/AKT/HIF-1α axis.

Tartary buckwheat is a cereal crop that has both medicinal and food origins. However, the underlying factors that contribute to Tartary buckwheat’s flowering and seed-setting characteristics, effective grain formation, and physiological changes are still not well understood. This study aimed to investigate the flowering and seed-setting characteristics of different parts of Tartary buckwheat, as well as the grain-filling characteristics after flowering. To achieve this, Tartary buckwheat cultivars with high (QK3) and low (XQ2) seed-setting rates were selected for pot and field experiments. The study found that Tartary buckwheat undergoes flowering and seed setting simultaneously. Many wilted flowers and grains were observed 45 and 51 d after flowering. Compared to XQ2, QK3 exhibited a higher grain formation rate and seed-setting rate by 7.42% and 26.16%, respectively. Additionally, QK3 had a significantly lower grain abortion rate by 12.03%. The 1000-grain weight and average grain-filling rate of QK3 were 11.10% and 14.81% higher than those of XQ2, respectively. QK3 exhibited a faster maximum grain-filling rate (Rmax), reaching 18.38% faster than XQ2. Additionally, the dry matter average distribution rate in the main stem and branched grains of QK3 was 13.26% and 23.07% higher than that of XQ2, respectively. The sucrose concentration, SS, and SSS enzyme activities of QK3 were all higher than those of XQ2, by 0.29–25.99%, 5.22–11.62%, and 6.64–12.47%, respectively. Correlation analysis revealed a significant positive correlation between sucrose, soluble sugar, and starch concentration during the grain formation process and SS and SSS activities. This suggests that the levels of SS, SSS, soluble sugar, and sucrose in the grain play a crucial role in grain filling.

Abstract Background Increasing evidence has been confirmed that small nucleolar RNAs (SnoRNAs) play critical roles in tumorigenesis and exhibit prognostic value in clinical practice. However, there is short of systematic research on SnoRNAs in ovarian cancer (OV). Material/Methods 379 OV patients with RNA‐Seq and clinical parameters from TCGA database and 5 paired clinical OV tissues were embedded in our study. Cox regression analysis was used to identify prognostic SnoRNAs and construct prediction model. SNORic database was adopted to examine the copy number variation of SnoRNAs. ROC curves and KM plot curves were applied to validate the prognostic model. Besides, the model was validated in 5 paired clinical tissues by real‐time PCR, H&E staining and immunohistochemistry. Results A prognostic model was constructed on the basis of SnoRNAs in OV patients. Patients with higher RiskScore had poor clinicopathological parameters, including higher age, larger tumor size, advanced stage and with tumor status. KM plot analysis confirmed that patients with higher RiskScore had poorer prognosis in subgroup of age, tumor size, and stage. 7 of 9 SnoRNAs in the prognostic model had positive correlation with their host genes. Moreover, 5 of 9 SnoRNAs in the prognostic model correlated with their CNVs, and SNORD105B had the strongest correction with its CNVs. ROC curve showed that the RiskScore had excellent specificity and accuracy. Further, results of H&E staining and immunohistochemistry of Ki67, P53 and P16 confirmed that patients with higher RiskScore are more malignant. Conclusions In summary, we identified a nine‐SnoRNAs signature as an independent indicator to predict prognosis of OV, providing a prospective prognostic biomarker and potential therapeutic targets for ovarian cancer.

IntroductionThe underlying pathophysiological mechanisms of cerebral ischemia reperfusion injury (CIRI) is intricate, and current studies suggest that neuron, astrocyte, microglia, endothelial cell, and pericyte all have different phenotypic changes of specific cell types after ischemic stroke. And microglia account for the largest proportion after CIRI. Previous transcriptomic studies of ischemic stroke have typically focused on the 24 hours after CIRI, obscuring the dynamics of cellular subclusters throughout the disease process. Therefore, traditional methods for identifying cell types and their subclusters may not be sufficient to fully unveil the complexity of single-cell transcriptional profile dynamics caused by an ischemic stroke.MethodsIn this study, to explore the dynamic transcriptional profile of single cells after CIRI, we used single-cell State Transition Across-samples of RNA-seq data (scSTAR), a new bioinformatics method, to analyze the single-cell transcriptional profile of day 1, 3, and 7 of transient middle cerebral artery occlusion (tMCAO) mice. Combining our bulk RNA sequences and proteomics data, we found the importance of the integrin beta 2 (Itgb2) gene in post-modeling. And microglia of Itgb2+ and Itgb2- were clustered by the scSTAR method. Finally, the functions of the subpopulations were defined by Matescape, and three different time points after tMCAO were found to exhibit specific functions.ResultsOur analysis revealed a dynamic transcriptional profile of single cells in microglia after tMCAO and explored the important role of Itgb2 contributed to microglia by combined transcriptomics and proteomics analysis after modeling. Our further analysis revealed that the Itgb2+ microglia subcluster was mainly involved in energy metabolism, cell cycle, angiogenesis, neuronal myelin formation, and repair at 1, 3, and 7 days after tMCAO, respectively.DiscussionOur results suggested that Itgb2+ microglia act as a time-specific multifunctional immunomodulatory subcluster during CIRI, and the underlying mechanisms remain to be further investigated.

Throughfall (TF) is an important water input of rainfall redistribution into floor, and its spatial–temporal variability under some species' canopies has been documented to evaluate effect on splash erosion. However, the understanding of TF variability under large broad-leaved canopy remains insufficient. In this study, the spatial heterogeneity, temporal stability and drop size of TF were quantified using variogram fitting, normalised ranking and filter paper staining, respectively, under banana (Musa nana Lour.) canopy comprising long and wide leaves. Results indicated TF pattern showed strong spatial correlation at a range of 3–5 m. High spatial variability of TF was found, which was affected by rainfall event size and was accompanied by great canopy disturbance. TF plots revealed high time variability, which was mainly controlled by unstable banana canopy structure. TF drop size from leaf dripping points varied in 3–10 mm and showed significant differences (p < 0.05) among five kinds of leaf shapes, implying that concave and broken banana leaves were involved in the variability of TF drop size. Overall, results demonstrate the spatial–temporal variability of TF is dramatically induced by banana canopy with broad leaves, which may result in non-uniform soil water content and splash erosion under the canopy. HIGHLIGHTS The specific banana canopy notably modifies spatial-temporal variability of throughfall.; The spatial variability of throughfall was high and correlated with the rainfall event size.; The spatial pattern of throughfall showed low time stability based on multi-temporal levels.; Drop size of throughfall at different leaf shapes showed variable distribution in 3–10 mm.;

BackgroundWhole-cell tumor vaccines tend to suffer from low immunogenicity. Our previous study showed that irradiated lung cancer cell vaccines in mouse models enhance antitumor efficacy by eliciting an intensive T cells response and improving immunogenicity. Based on these findings, we developed an improved whole-cell tumor vaccine, Autologous Tumor Holo antigEn immuNe Activation (ATHENA).MethodsIn this study, we report the successful treatment of a 6-year-old male diagnosed with meningeal rhabdomyosarcoma with pulmonary and liver metastases using ATHENA. After 6 cycles of therapy, PET/CT showed the therapeutic efficacy of ATHENA. We profiled the immune response by single-cell RNA sequencing (scRNA-seq). Flow cytometry analysis was implemented to validate the status transitions of CD8+ T cells.ResultsIn CD8+ T cells, the exhausted status was weakened after treatment. The exhausted CD4+ T cells shifted towards the central memory phenotype after the treatment. Breg cells were converted to Plasma or Follicular B cells. Survival analysis for pan-cancer and transcription factor analysis indicated that such T cell and B cell transitions represent the recovery of antitumoral adaptive immune response. We validated that the proportion of CD279+CD8+ T cells were reduced and the expression of CD44 molecule was upregulated by flow cytometry assay.ConclusionSuch studies not only show that ATHENA therapy may be a promising alternative treatment for tumor patients but provide a novel idea to analyses the mechanisms of rare cases or personalized cancer treatment.

Most patients with clear cell renal cell carcinoma (ccRCC) have an impaired response to immune checkpoint blockade (ICB) therapy. Few biomarkers can predict responsiveness, and there is insufficient evidence to extend them to ccRCC clinical use. To explore subtypes and signatures of immunocytes with good predictive performance for ICB outcomes in the ccRCC context, we reanalyzed two ccRCC single-cell RNA sequencing (scRNA-seq) datasets from patients receiving ICB treatment. A subtype of proliferative CD4+ T cells and regulatory T cells and a subtype of antigen-presenting monocytes that have good predictive capability and are correlated with ICB outcomes were identified. These findings were corroborated in independent ccRCC ICB pretreatment bulk RNA-seq datasets. By incorporating the cluster-specific marker genes of these three immunocyte subtypes, we developed a prediction model, which reached an AUC of 93% for the CheckMate cohort (172 samples). Our study shows that the ICB response prediction model can serve as a valuable clinical decision-making tool for guiding ICB treatment of ccRCC patients.

The entrance and exit of loess tunnel are easily affected by freezing and thawing, which leads to collapse in cold regions. Based on the slip line network method, this paper proposed a graphical method and analyzed the impact of evaluation of freeze–thaw cycles on the collapse zone at the entrance and exit of a loess tunnel. Firstly, the slip line network method was improved for a graphical calculation program, and the program was validated by monitoring the data of collapse evolution in an unlined loess tunnel in situ. Then, some triaxial tests of freeze–thaw cycles were carried out on loess, and the attenuation law of loess strength was summarized after freeze–thaw cycles in cold regions. Finally, the graphical calculation program was applied to evaluate the impact of freeze–thaw cycles on collapse range in the unlined loess tunnel. The results show that introducing the classic slip line field into the analysis process of a tunnel collapse zone can provide a feasible and efficient analysis method for a tunnel surrounding rock collapse arch for tunnel engineering, and the collapse zone increases with the growing number of freeze–thaw cycles. Moreover, the attenuation of loess strength which suffered from the freeze–thaw cycles would cause the collapse zone area to increase by a maximum of 16.13%.

NBS-LRR genes are the largest gene family in plants conferring resistance to pathogens. At present, studies on the evolution of NBS-LRR genes in angiosperms mainly focused on monocots and eudicots, while studies on NBS-LRR genes in the basal angiosperms are limited. Euryale ferox represents an early-diverging angiosperm order, Nymphaeales, and confronts various pathogens during its lifetime, which can cause serious economic losses in terms of yield and quality. In this study, we performed a genome-wide identification and analysis of NBS-LRR genes in E. ferox. All 131 identified NBS-LRR genes could be divided into three subclasses according to different domain combinations, including 18 RNLs, 40 CNLs, and 73 TNLs. The E. ferox NBS-LRR genes are unevenly distributed on 29 chromosomes; 87 genes are clustered at 18 multigene loci, and 44 genes are singletons. Gene duplication analysis revealed that segmental duplications acted as a major mechanism for NBS-LRR gene expansions but not for RNL genes, because 18 RNL genes were scattered over 11 chromosomes without synteny loci, indicating that the expansion of RNL genes could have been caused by ectopic duplications. Ancestral gene reconciliation based on phylogenetic analysis revealed that there were at least 122 ancestral NBS-LRR lineages in the common ancestor of the three Nymphaeaceae species, suggesting that NBS-LRR genes expanded slightly during speciation in E. ferox. Transcriptome analysis showed that the majority of NBS-LRR genes were at a low level of expression without pathogen stimulation. Overall, this study characterized the profile of NBS-LRR genes in E. ferox and should serve as a valuable resource for disease resistance breeding in E. ferox.

Abstract. Objective:. Laboratory diagnosis of neurosyphilis (NS) remains a great challenge. This study was the aimed to identify miRNA candidates as biomarkers to distinguish between NS, non-neurosyphilis, and healthy controls (HCs). Methods:. We analyzed miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from six patients with NS, eight patients with secondary syphilis (SS), and five HCs using microarray technology. The differentially expressed miRNAs were validated in 33 NS samples, 31 SS samples, and 30 HC samples using TaqMan miRNA real-time qPCR (qRT-PCR). Results:. Thirty-nine miRNAs were differentially expressed in SS and NS patients compared with HCs. Thirteen miRNAs were randomly selected to validate their expression levels in the same samples used in microarray assay by qRT-PCR. All miRNAs were upregulated in SS and NS samples compared with HC. qRT-PCR analysis of the expression of the 13 miRNAs in a second cohort (76 samples) showed that the average expression levels of nine miRNAs were higher in SS than in NS (SS: 0.185, NS: 0.136, P=3.8E-10), while the expressions of the other four miRNAs were lower in SS than in NS (SS: 0.000757, NS: 0.000873, P=0.022). ROC curve analysis of the 13 miRNAs showed the area under the curve value to be 1.00 for distinguishing SS patients from HCs, 1.00 for distinguishing NS patients from HCs, 1.00 for distinguishing SS and NS patients from HCs, and 0.968 for distinguishing NS from SS patients. Conclusion:. The present study is the first one that identified differentially expressed miRNAs in PBMCs from patients with NS. Our results suggest that the 13 candidate miRNAs in PBMCs may be novel noninvasive biomarkers for NS diagnosis.

Abstract Genetic heterogeneity of tumor is closely related to its clonal evolution, phenotypic diversity and treatment resistance, and such heterogeneity has only been characterized at single-cell sub-chromosomal scale in liver cancer. Here we reconstructed the single-variant resolution clonal evolution in human liver cancer based on single-cell mutational profiles. The results indicated that key genetic events occurred early during tumorigenesis, and an early metastasis followed by independent evolution was observed in primary liver tumor and intrahepatic metastatic portal vein tumor thrombus. By parallel single-cell RNA-Seq, the transcriptomic phenotype of HCC was found to be related with genetic heterogeneity. For the first time we reconstructed the single-cell and single-variant clonal evolution in human liver cancer, and dissection of both genetic and phenotypic heterogeneity will facilitate better understanding of their relationship.

In this paper, the dynamic coupling between the wind turbine rotor speed recovery (WTRSR) and inertial response of the conventional virtual synchronous generator (VSG) controlled wind farms (WFs) is analyzed. Three distinguishing features are revealed. Firstly, the inertial response characteristics of VSG controlled WFs (VSG-WFs) are impaired by the dynamic coupling. Secondly, when the influence of WTRSR is dominant, the inertial response characteristics of VSG-WFs are even worse than the condition under which WFs do not participate in the response of grid frequency. Thirdly, this phenomenon cannot be eliminated by only enlarging the inertia parameter of VSG-WFs, because the influence of WTRSR would also increase with the enhancement of inertial response. A decou-pling scheme to eliminate the negative influence is then proposed in this paper. By starting the WTRSR process after inertial response period, the dynamic coupling is eliminated and the inertial response characteristics of WFs are improved. Finally, the effectiveness of the analysis and the proposed scheme are verified by simulation results.

Annulus pressure control is critical to well safety in deepwater oil and gas wells, and it is crucial for deepwater high-pressure oil and gas wells, which are related to production safety. At present, the deepwater annular pressure analysis model is mainly based on the trapped annulus principle. For the high annular pressure of deepwater high-pressure oil and gas wells, it brings great management and control challenges. This paper proposes a deepwater high-pressure oil and gas well annular pressure analysis method considering formation connectivity. According to the existing measures of annular pressure management and control, the differences between various types of annular pressure management and control technology are systematically analyzed and expounded, and the annular pressure management and control technology of deepwater high-pressure oil and gas wells is proposed accordingly. At the same time, combined with the actual case of a deepwater high-pressure well in the South China Sea, the annular pressure considering different influencing factors is analyzed, and the appropriate management and control methods of annular pressure are recommended. This paper systematically summarizes and studies the analysis and control technology of annular pressure in deepwater high-pressure oil and gas wells, which provides a technical basis for China’s deep water to move from conventional deepwater to deepwater high-pressure, and can provide a reference for the management and control of annular pressure in oil and gas wells in subsequent deepwater projects.

Understanding the tumour microenvironment is essential for the efficacy of immunotherapies. Here the authors describe the immune landscape in esophageal squamous cell carcinoma and suggest several immunosuppressive mechanisms, which upon targeting may restore anti-tumour immune response.

This study aims to investigate the risk factors associated with impaired pulmonary diffusing capacity among patients with noncystic fibrosis bronchiectasis (NCFB) and compare the predictive value of several scoring systems for the impairment in these patients. Between July 2019 and June 2021, patients who were admitted to the hospital and diagnosed with NCFB were included in this study. Clinical data were collected and analyzed retrospectively. A total of 175 NCFB patients were included in the analysis. Multivariate logistic regression analysis revealed that impaired pulmonary diffusing capacity diagnosed by carbon monoxide diffusing capacity (DLCO)

Abstract Background High-throughput sequencing technology has yielded reliable and ultra-fast sequencing for DNA and RNA. For tumor cells of cancer patients, when combining the results of DNA and RNA sequencing, one can identify potential neoantigens that stimulate the immune response of the T cell. However, when the somatic mutations are abundant, it is computationally challenging to efficiently prioritize the identified neoantigen candidates according to their ability of activating the T cell immuno-response. Methods Numerous prioritization or prediction approaches have been proposed to address this issue but none of them considers the original DNA loci of the neoantigens from the perspective of 3D genome. Based on our previous discoveries, we propose to investigate the distribution of neoantigens with different immunogenicity abilities in 3D genome and propose to adopt this important information into neoantigen prediction. Results We retrospect the DNA origins of the immuno-positive and immuno-negative neoantigens in the context of 3D genome and discovered that DNA loci of the immuno-positive neoantigens and immuno-negative neoantigens have very different distribution pattern. Specifically, comparing to the background 3D genome, DNA loci of the immuno-positive neoantigens tend to locate at specific regions in the 3D genome. We thus used this information into neoantigen prediction and demonstrated the effectiveness of this approach. Conclusion We believe that the 3D genome information will help to increase the precision of neoantigen prioritization and discovery and eventually benefit precision and personalized medicine in cancer immunotherapy.

In recent years, the deep learning is applied to the field of traffic sign detection methods which achieves excellent performance. However, there are two main challenges in traffic sign detection to be solve urgently. For one thing, some traffic signs of small size are more difficult to detect than those of large size so that the small traffic signs are undetected. For another, some false signs are always detected because of interferences caused by the illumination variation, bad weather and some signs similar to the true traffic signs. Therefore, to solve the undetection and false detection, we first propose a cascaded R-CNN to obtain the multiscale features in pyramids. Each layer of the cascaded network except the first layer fuses the output bounding box of the previous one layer for joint training. This method contributes to the traffic sign detection. Then, we propose a multiscale attention method to obtain the weighted multiscale features by dot-product and softmax, which is summed to fine the features to highlight the traffic sign features and improve the accuracy of the traffic sign detection. Finally, we increase the number of difficult negative samples for dataset balance and data augmentation in the training to relieve the interference by complex environment and similar false traffic signs. The data augment method expands the German traffic sign training dataset by simulation of complex environment changes. We conduct numerous experiments to verify the effectiveness of our proposed algorithm. The accuracy and recall rate of our method are 98.7% and 90.5% in GTSDB, 99.7% and 83.62% in CCTSDB and 98.9% and 85.6% in Lisa dataset respectively.

Background: At present, the global sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) situation is still grim, and the risk of local outbreaks caused by imported viruses is high. Therefore, it is necessary to monitor the genomic variation and genetic evolution characteristics of SARS-CoV-2. The main purpose of this study was to detect the entry of different SARS-CoV-2 variants into Jiangsu Province, China.Methods: First, oropharyngeal swabs were collected from 165 patients (55 locally confirmed cases and 110 imported cases with confirmed and asymptomatic infection) diagnosed with SARS-CoV-2 infection in Jiangsu Province, China between January 2020 and June 2021. Then, whole genome sequencing was used to explore the phylogeny and find potential mutations in genes of the SARS-CoV-2. Last, association analysis among clinical characteristics and SARS-CoV-2 Variant of Concern, pedigree surveillance analysis of SARS-COV-2, and single nucleotide polymorphisms (SNPs) detection in SARS-COV-2 samples was performed.Results: More men were infected with the SARS-CoV-2 when compared with women. The onset of the SARS-CoV-2 showed a trend of younger age. Moreover, the number of asymptomatic infected patients was large, similar to the number of common patients. Patients infected with Alpha (50%) and Beta (90%) variants were predominantly asymptomatic, while patients infected with Delta (17%) variant presented severe clinical features. A total of 935 SNPs were detected in 165 SARS-COV-2 samples. Among which, missense mutation (58%) was the dominant mutation type. About 56% of SNPs changes occurred in the open reading frame 1ab (ORF1ab) gene. Approximately, 20% of SNP changes occurred in spike glycoprotein (S) gene, such as p.Asp501Tyr, p.Pro681His, and p.Pro681Arg. In total, nine SNPs loci in S gene were significantly correlated with the severity of patients. It is worth mentioning that amino acid substitution of p.Asp614Gly was significantly positively correlated with the clinical severity of patients. The amino acid replacements of p.Ser316Thr and p.Lu484Lys were significantly negatively correlated with the course of disease.Conclusion: Sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may further undergo a variety of mutations in different hosts, countries, and weather conditions. Detecting the entry of different virus variants of SARS-CoV-2 into Jiangsu Province, China may help to monitor the spread of infection and the diversity of eventual recombination or genomic mutations.

Secale cereale is an important crop in the Triticeae tribe of the Poaceae family, and it has unique agronomic characteristics and genome properties. It possesses resistance to many diseases and serves as an important resource for the breeding of other Triticeae crops. We performed a genome-wide study on S. cereale to identify the largest group of plant disease resistance genes (R genes), the nucleotide-binding site-leucine-rich repeat receptor (NBS-LRR) genes. In its genome, 582 NBS-LRR genes were identified, including one from the RNL subclass and 581 from the CNL subclass. The NBS-LRR gene number in the S. cereale genome is greater than that in barley and the diploid wheat genomes. S. cereale chromosome 4 contains the largest number of NBS-LRR genes among the seven chromosomes, which is different from the pattern in barley and the genomes B and D of wheat but similar to that in the genome A of wheat. Further synteny analysis suggests that more NBS-LRR genes on chromosome 4 have been inherited from a common ancestor by S. cereale and the wheat genome A than the wheat genomes B and D. Phylogenetic analysis revealed that at least 740 NBS-LRR lineages are present in the common ancestor of S. cereale, Hordeum vulgare and Triticum urartu. However, most of them have only been inherited by one or two species, with only 65 of them preserved in all three species. The S. cereale genome inherited 382 of these ancestral NBS-LRR lineages, but 120 of them have been lost in both H. vulgare and T. urartu. This study provides the full NBS-LRR profile of the S. cereale genome, which is a resource for S. cereale breeding and indicates that S. cereale can be an important material for the molecular breeding of other Triticeae crops.

ABSTRACT To assess the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies produced by natural infection and describe the serological characteristics over 7 months after symptom onset among coronavirus disease 2019 (COVID-19) patients by age and severity group, we followed up COVID-19 convalescent patients confirmed from 1 January to 20 March 2020 in Jiangsu, China and collected serum samples for testing IgM/IgG and neutralizing antibodies against SARS-CoV-2 between 26 August and 28 October 2020. In total, 284 recovered participants with COVID-19 were enrolled in our study. Patients had a mean age of 46.72 years (standard deviation [SD], 17.09), and 138 (48.59%) were male. The median follow-up time after symptom onset was 225.5 (interquartile range [IQR], 219 to 232) days. During the follow-up period (162 to 282 days after symptom onset), the seropositive rate of IgM fluctuated around 25.70% (95% confidence interval [CI], 20.72% to 31.20%) and that of IgG fluctuated around 79.93% (95% CI, 74.79% to 84.43%). Of the 284 patients, 64 participants were tested when discharged from hospital. Compared with that at the acute phase, the IgM/IgG antibody levels and IgM seropositivity have decreased; however, the seropositivity of IgG was not significantly lower at this follow-up (78.13% versus 82.81%). Fifty percent inhibitory dilution (ID50) titers of neutralizing antibody for samples when discharged from hospital (geometric mean titer [GMT], 82; 95% CI, 56 to 121) were significantly higher than those at 6 to 7 months after discharge (GMT, 47; 95% CI, 35 to 63) (P

Moyamoya disease (MMD) is an occlusive, chronic cerebrovascular disease affected by genetic mutation and the immune response. Furthermore, vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) participate in the neointima of MMD, but the etiology and pathophysiological changes in MMD vessels remain largely unknown. Therefore, we established the circZXDC (ZXD family zinc finger C)–miR-125a-3p–ABCC6 (ATP-binding cassette subfamily C member 6) axis from public datasets and online tools based on “sponge-like” interaction mechanisms to investigate its possible role in VSMCs. The results from a series of in vitro experiments, such as dual luciferase reporter assays, cell transfection, CCK-8 assays, Transwell assays, and Western blotting, indicate a higher level of circZXDC in the MMD plasma, especially in those MMD patients with the RNF213 mutation. Moreover, circZXDC overexpression results in a VSMC phenotype switching toward a synthetic status, with increased proliferation and migration activity. CircZXDC sponges miR-125a-3p to increase ABCC6 expression, which induces ERS (endoplasmic reticulum stress), and subsequently regulates VSMC transdifferentiation from the contractive phenotype to the synthetic phenotype, contributing to the intima thickness of MMD vessels. Our findings provide insight into the pathophysiological mechanisms of MMD and indicate that the circZXDC–miR-125a-3p–ABCC6 axis plays a pivotal role in the progression of MMD. Furthermore, circZXDC might be a diagnostic biomarker and an ABCC6-specific inhibitor and has the potential to become a promising therapeutic option for MMD.

Polycystic ovarian syndrome (PCOS) is a reproductive, endocrine, and metabolic disorder. Circulating markers of oxidative stress are abnormal in women with PCOS. There is a close relationship between oxidative stress and insulin resistance (IR). However, little information is available about oxidative stress in the skeletal muscles of those affected by PCOS. In this study, PCOS was induced in prepubertal C57BL/6J mice by injection with dehydroepiandrosterone. Oxidative stress biomarkers were then measured in both serum and skeletal muscles. The underlying mechanisms were investigated in C2C12 myotubes treated with testosterone (T). We discovered increased oxidative biomarkers, increased ROS production, and damaged insulin sensitivity in the skeletal muscles of mice with PCOS. High levels of T caused mitochondrial dysfunction and increased ROS levels through the androgen receptor (AR)-nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) signaling pathway in C2C12 cells. Treatment of C2C12 cells with an antioxidant N-acetylcysteine (NAC) decreased T-induced ROS production, improved mitochondrial function, and reversed IR. Administration of NAC to mice with PCOS improved insulin sensitivity in the skeletal muscles of the animals. Hyperandrogenism caused mitochondrial dysfunction and redox imbalance in the skeletal muscles of mice with PCOS. We discovered that oxidative stress contributed to skeletal muscle IR in PCOS. Reducing ROS levels may improve the insulin sensitivity of skeletal muscles in patients with PCOS.

To characterize human leukocyte antigen (HLA) loci as risk factors in aromatic antiepileptic drug-induced maculopapular exanthema (AED-MPE). A case-control study was performed to investigate HLA loci involved in AED-MPE in a southern Han Chinese population. Between January 2007 and June 2019, 267 patients with carbamazepine (CBZ), oxcarbazepine (OXC), or lamotrigine (LTG) associated MPE and 387 matched drug-tolerant controls from six centers were enrolled. HLA-A/B/C/DRB1 genotypes were determined using sequence-based typing. Potential risk alleles were validated by meta-analysis using data from different populations and in silico analysis of protein-drug interactions. HLA-DRB1*04:06 was significantly associated with OXC-MPE (p = 0.002, pc = 0.04). HLA-B*38:02 was associated with CBZ-MPE (p = 0.03). When pooled, HLA-A*24:02, HLA-A*30:01, and HLA-B*35:01 additionally revealed significant association with AED-MPE. Logistic regression analysis showed a multiplicative interaction between HLA-A*24:02 and HLA-B*38:02 in CBZ-MPE. Meta-analysis of data from different populations revealed that HLA-24*:02 and HLA-A*30:01 were associated with AED-MPE (p = 0.02 and p = 0.04, respectively). In silico analysis of protein-drug interaction demonstrated that HLA-A*24:02 and HLA-A*30:01 had higher affinities with the three aromatic AEDs than the risk-free HLA-A allele. HLA-DRB1*04:06 showed relatively specific high affinity with S-monohydroxy derivative of OXC. HLA-DRB1*04:06 is a specific risk allele for OXC-induced MPE in the Southern Han Chinese. HLA-A*24:02, possibly HLA-A*30:01, are common risk factors for AED-MPE. The multiplicative risk potential between HLA-A*24:02 and HLA-B*38:02 suggests that patients with two risk alleles are at greater risk than those with one risk allele. Inclusion of these HLA alleles in pre-treatment screening would help estimating the risk of AED-MPE.

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease and is characterized by excessive hepatic lipid accumulation. Many studies have suggested that lipid overload is the key initial factor that contributes to hepatic steatosis. Our previous study indicated that diosgenin (DSG) has a beneficial effect on energy metabolism, but the underlying mechanism remains unclear. Methods Human normal hepatocytes (LO2 cells) were incubated with palmitic acid to establish the cell model of nonalcoholic fatty liver. The effects of DSG on lipid metabolism, glucose uptake and mitochondrial function were evaluated. Furthermore, the mechanism of DSG on oxidative stress, lipid consumption and lipid synthesis in LO2 cells was investigated. Results The results indicated that palmitic acid induced obvious lipid accumulation in LO2 cells and that DSG treatment significantly reduced the intracellular lipid content. DSG treatment upregulated expression of lipolysis proteins, including phospho-AMP activated protein kinase (p-AMPK), phospho-acetyl-coA carboxylase (p-ACC) and carnitine acyl transferase 1A (CPT-1A), and inhibited expression of lipid synthesis-related proteins, including sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS). Additionally, DSG-treated cells displayed a marked improvement in mitochondrial function, with less production of reactive oxygen species and a higher mitochondrial membrane potential compared with the model group. Conclusion This study suggests that DSG can reduce intracellular lipid accumulation in LO2 cells and that the underlying mechanism may be related to the improving oxidative stress, increasing fatty acid β-oxidation and decreasing lipid synthesis. The above changes might be mediated by the activation of the AMPK/ACC/CPT-1A pathway and inhibition of the SREBP-1c/FAS pathway.