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Abstract Background Several studies have confirmed the potential value of applying radiomics to predict prognosis of breast cancer. However, the tumor segmentation in these studies depended on delineation or annotation of breast cancer by radiologist, which is often laborious, tedious, and vulnerable to inter- and intra-observer variability. Automatic segmentation is expected to overcome this difficulty. Herein, we aim to investigate the value of automatic segmentation-based multi-modal radiomics signature and magnetic resonance imaging (MRI) features in predicting disease-free survival (DFS) of patients diagnosed with invasive breast cancer. Methods This retrospective multicenter study included a total of 643 female patients with invasive breast cancer who underwent preoperative ultrasound (US) and MRI for prognostic analysis. Data (n = 480) from center 1 were divided into training and internal testing sets, while data (n = 163) from centers 2 and 3 were analyzed as the external testing set. We developed automatic segmentation frameworks for tumor segmentation by deep learning. Then, Least absolute shrinkage and selection operator Cox regression was used to select features to construct radiomics signature, and corresponding radiomics score (Rad-score) was calculated. Finally, six models for predicting DFS were constructed by using Cox regression and assessed in terms of discrimination, calibration, and clinical usefulness. Results The multi-modal radiomics signature combining intra- and peri-tumoral radiomics signatures of US and MRI achieved a higher C-index in the internal (0.734) and external (0.708) testing sets than most other radiomics signatures in predicting DFS, and successfully stratified patients into low- and high-risk groups. The multi-modal clinical imaging model combining the multi-modal Rad-score and clinical traditional MRI model-score resulted in a higher C-index (0.795) than other models in the external testing set, and it had a better calibration and higher clinical benefit. Conclusions This study demonstrates that the multi-modal radiomics signature derived from automatic segmentations of US and MRI is a promising risk stratification biomarker for breast cancer, and highlights that the appropriate combination of multi-modal radiomics signature, clinical characteristics, and MRI feature can improve performance of individualized DFS prediction, which might assist in guiding decision-making related to breast cancer.

Abstract Background Long non-coding RNA (lncRNA) plays a vital role in the occurrence and development of varieties of tumors. Previous studies have shown that lncRNA GClnc1 is highly expressed in osteosarcoma (OS). However, the mechanism of lncRNA GClnc1 in osteosarcoma has not been fully elucidated. In this study, we investigated the biological roles of lncRNA GClnc1 in osteosarcoma and unveiled its underlying mechanisms. Methods The expression of lncRNA GClnc1 in OS cells was detected by real-time quantitative PCR (qRT-PCR). The functional roles of lncRNA GClnc1 were examined by CCK8, trans-well, scratch wound healing assay, colony formation, and apoptosis assays in osteosarcoma cells upon silencing or overexpressing GClnc1. Western blot analysis, qRT-PCR, and RNA co-immunoprecipitation (RIP) assays were used to detect the interaction between lncRNA GClnc1 and NONO. Results The expression of lncRNA GClnc1 was up-regulated in osteosarcoma cell lines. Knockdown of lncRNA GClnc1 suppressed the cell growth, migration, and invasion of OS cells, whereas the over-expression of GClnc1 improved the proliferation, migration, and invasion of OS cells. Mechanistically, we identified that lncRNA GClnc1 regulates the stability of NONO by blocking FBXW7-mediated ubiquitination degradation. Additionally, overexpression of NONO can reverse GClnc1 silencing exerted suppression of the cell proliferation, migration, and invasion, and vice versa. Conclusions Our study elucidated that lncRNA GClnc1 participates in the progression of OS by regulating the NONO signal pathway. Targeting GClnc1 provides a potential target for future clinical treatment of OS.

Abstract Evidences regarding the feasibility of transcatheter arterial chemoembolization (TACE)-based therapy for unresectable hepatocellular carcinoma (uHCC) remains limited. This study aimed to investigate the efficacy and safety of TACE combined with envafolimab and lenvatinib for uHCC. Eligible patients with uHCC received envafolimab and lenvatinib after TACE until disease progression, conversion to surgery, intolerable toxicities, or death. The primary endpoint was the objective response rate (ORR) assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Between March 2022 and July 2022, 38 patients were included for safety analysis, and 36 patients were included for efficacy analysis. As of the data cutoff (13 December 2023), the median follow-up was 16.9 months. The ORR was 50%, and disease control rate (DCR) was 83.3% per RECIST 1.1 (ORR and DCR of both 83.3% per modified RECIST (mRECIST)). The median progression-free survival (PFS) was 7.58 months. Of 36 patients, 17 patients were converted to resectable HCC with a surgical conversion rate of 47.2%, and 16 patients underwent surgery with R0 resection rate of 100%, pathologic complete response (pCR) rate of 31.3%. Overall incidences of treatment-related adverse events (TRAEs) of any grade was 97.4%. Grade ≥ 3 TRAEs were observed in 52.6% patients. No treatment-related deaths occurred. Image mass cytometry (IMC) analysis revealed that combined treatment improved the immune status of the tumor microenvironment, and resident macrophages had the potential to predict efficacy of this treatment. Envafolimab plus lenvatinib and TACE yielded promising survival outcomes and conversion efficiency with a tolerable safety profile. Trial registration Clinical trials: NCT05213221.

Lung cancer is the most common malignant tumor in China. Its incidence and mortality rate increase year by year. In the synthesis treatment of lung cancer, radiotherapy (RT) plays a vital role, and radiation-induced lung injury(RILI) has become the major limiting factor in prescription dose escalation. Conventional RT is designed to minimize radiation exposure to healthy lungs without considering the inhomogeneity of lung function, which is significantly non-uniform in most patients. In accordance with the functional and structural heterogeneity of lung tissue, functional lung avoidance RT (FLART) can reduce radiation exposure to functional lung (FL), thus reducing RILI. Meanwhile, a dose-function histogram (DFH) was proposed to describe the dose parameters of the optimized image-guided RT plan. This paper reviews lung function imaging for lung cancer RT plans. It also reviews the clinical applications of function-guided RT plans and their current problems and research directions to provide better guidance for clinical selection.

BackgroundPatients with primary aldosteronism present with renal function decline after unilateral adrenalectomies. Our study aimed to assess the evolution of renal function after adrenalectomy in patients with primary aldosteronism across different age groups and to identify risk factors for postoperative renal function deterioration.MethodsWe included 210 patients with primary aldosteronism categorized into three age groups:

Diaporthe spp. are a significant plant pathogen causing wood canker, blight, dieback, and fruit decay in numerous economically important plant hosts worldwide. D. nobilis has been identified as a highly pathogenic isolate responsible for causing kiwifruit (Actinidia spp.) rot, representing one of the most significant threats to the kiwifruit industry. Here, a comprehensive genome-wide sequence of D. nobilis strain DJY16A 5-1 utilizing advanced Nanopore third-generation sequencing technology is presented. The genome of D. nobilis strain DJY16A 5-1 was assembled into 26 contigs containing a combined size of 59.28 Mb and N50 length of 4.47 Mb. The virulence-related genes were analyzed, including 3,407 transmembrane proteins, 1,410 secreted proteins, 1,866 signal peptides, 135 effector proteins, 1,069 carbohydrate-active enzymes, 143 membrane transporter proteins, and 4,995 pathogen–host interaction-related proteins. The genome assembly and annotation facilitate the analysis of pathogen–host interaction, laying the foundation for in-depth research on the infection mechanism of pathogens. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

The discharge of organic pollutants by the textile and dyeing industries presents an escalating threat to aquatic environments, necessitating the development of effective remediation strategies. This study introduces the utilization of graphite-like structured activated carbon (AC), derived from highland barley straw—a biomass unique to the Plateau regions of China, including Tibet, Qinghai, and Gansu—as a support material for the TiO2 catalyst. TiO2/AC composites with different TiO2 loadings were synthesized by ultrasonic impregnation. The TiO2/AC composites were found to be polycrystalline materials composed of anatase and rutile phases. The TiO2 nanoparticles are well-dispersed over the surface of the AC. The photocatalytic activity of these composites was evaluated through their capacity to degrade a methylene blue (MB) solution upon irradiation. It was observed that the inclusion of TiO2 increases the number of adsorption sites and active sites for methylene blue, with the photocatalytic activity being notably higher at a 3-wt% TiO2 loading, achieving a remarkable 99.6 % degradation efficiency for 100 mg/L MB within 100 min. The experimental kinetic data for the photocatalytic process follow the pseudo-first-order kinetic model. Furthermore, TiO2/AC retains high photocatalytic activity after five reaction cycles. This research provides valuable insights into the application of biomass-derived materials for the purification of water, offering a sustainable solution to both pollution and agricultural waste challenges in Plateau areas of China.

Bisphenol A (BPA), representing a class of organic pollutants, finds extensive applications in the pharmaceutical industry. However, its widespread use poses a significant hazard to both ecosystem integrity and human health. Advanced oxidation processes (AOPs) based on peroxymonosulfate (PMS) via heterogeneous catalysts are frequently proposed for treating persistent pollutants. In this study, the degradation performance of BPA in an oxidation system of PMS activated by transition metal sites anchored nitrogen-doped carbonaceous substrate (M-N-C) materials was investigated. As heterogeneous catalysts targeting the activation of peroxymonosulfate (PMS), M-N-C materials emerge as promising contenders poised to overcome the limitations encountered with traditional carbon materials, which often exhibit insufficient activity in the PMS activation process. Nevertheless, the amalgamation of metal sites during the synthesis process presents a formidable challenge to the structural design of M-N-C. Herein, employing ZIF-8 as the precursor of carbonaceous support, metal ions can readily penetrate the cage structure of the substrate, and the N-rich linkers serve as effective ligands for anchoring metal cations, thereby overcoming the awkward limitation. The research results of this study indicate BPA in water matrix can be effectively removed in the M-N-C/PMS system, in which the obtained nitrogen-rich ZIF-8-derived Cu-N-C presented excellent activity and stability on the PMS activation, as well as the outstanding resistance towards the variation of environmental factors. Moreover, the biological toxicity of BPA and its degradation intermediates were investigated via the Toxicity Estimation Software Tool (T.E.S.T.) based on the ECOSAR system.

Postharvest rot, caused by Penicillium expansum, in tomatoes poses significant economic and health risks. Traditional control methods, such as the use of fungicides, raise concerns about pathogen resistance, food safety, and environmental impact. In search of sustainable alternatives, plant secondary metabolites, particularly phenolic compounds and their derivatives, have emerged as promising natural antimicrobials. Among these, feruloyl glyceride (FG), a water-soluble derivative of ferulic acid, stands out due to its antioxidant properties, antibacterial properties, and improved solubility. In this study, we provide evidence demonstrating FG is capable of inhibiting the spore germination of P. expansum and effectively reducing the incidence rate of Penicillium rot of tomatoes, without compromising quality. Electron microscopy observations combined with metabolite and transcriptomic analyses revealed that FG treatments resulted in enhanced suberin accumulation through promoting the expression of suberin synthesis related genes and, consequently, inhibited the growth and expansion of P. expansum on the fruits. This work sheds light on the mechanisms underlying FG’s inhibitory effects, allowing its potential application as a natural and safe alternative to replace chemical fungicides for postharvest preservation.

IntroductionThe under representation of women in STEM fields is a persistent issue worldwide. In China, although women have made significant progress in pursuing STEM degrees in recent years, they continue to face challenges in the workforce. Given the importance of the self-perceived employability (SPE) of female STEM students in China, the research questions are: How do curriculum experience, extracurricular experience, and faculty supportive activities affect the SPE of female STEM students in Chinese universities? To what extent does university stratification affect the relationship between college experience and female STEM students’ SPE?MethodsWe analyzed the 2018 data of the Chinese College Student Survey (CCSS) consisting of a sample of 59,066 students, and six focus group interviews.ResultsThe findings suggest that curriculum experience, extracurricular experience and faculty supportive activities have a positive impact on the SPE of female students, but the gender gap in SPE is still valid as reflected by the fact that women have lower SPE than men in each tier of universities and that men benefit more in terms of the increase in SPE from most types of college activities and support except academic ones.DiscussionThis study reveals that the different tiers of universities in China affect female students’ SPE in different ways, and provides valuable evidence for academic as well as university administrators and policymakers regarding how college experience affect women and how university stratification can affect female students’ college experience and their career expectations and paths.

Summary: Background: For patients with early-stage breast cancers, neoadjuvant treatment is recommended for non-luminal tumors instead of luminal tumors. Preoperative distinguish between luminal and non-luminal cancers at early stages will facilitate treatment decisions making. However, the molecular immunohistochemical subtypes based on biopsy specimens are not always consistent with final results based on surgical specimens due to the high intra-tumoral heterogeneity. Given that, we aimed to develop and validate a deep learning radiopathomics (DLRP) model to preoperatively distinguish between luminal and non-luminal breast cancers at early stages based on preoperative ultrasound (US) images, and hematoxylin and eosin (H&E)-stained biopsy slides. Methods: This multicentre study included three cohorts from a prospective study conducted by our team and registered on the Chinese Clinical Trial Registry (ChiCTR1900027497). Between January 2019 and August 2021, 1809 US images and 603 H&E-stained whole slide images (WSIs) from 603 patients with early-stage breast cancers were obtained. A Resnet18 model pre-trained on ImageNet and a multi-instance learning based attention model were used to extract the features of US and WSIs, respectively. An US-guided Co-Attention module (UCA) was designed for feature fusion of US and WSIs. The DLRP model was constructed based on these three feature sets including deep learning US feature, deep learning WSIs feature and UCA-fused feature from a training cohort (1467 US images and 489 WSIs from 489 patients). The DLRP model's diagnostic performance was validated in an internal validation cohort (342 US images and 114 WSIs from 114 patients) and an external test cohort (270 US images and 90 WSIs from 90 patients). We also compared diagnostic efficacy of the DLRP model with that of deep learning radiomics model and deep learning pathomics model in the external test cohort. Findings: The DLRP yielded high performance with area under the curve (AUC) values of 0.929 (95% CI 0.865–0.968) in the internal validation cohort, and 0.900 (95% CI 0.819–0.953) in the external test cohort. The DLRP also outperformed deep learning radiomics model based on US images only (AUC 0.815 [0.719–0.889], p = 0.027) and deep learning pathomics model based on WSIs only (AUC 0.802 [0.704–0.878], p = 0.013) in the external test cohort. Interpretation: The DLRP can effectively distinguish between luminal and non-luminal breast cancers at early stages before surgery based on pretherapeutic US images and biopsy H&E-stained WSIs, providing a tool to facilitate treatment decision making in early-stage breast cancers. Funding: Natural Science Foundation of Guangdong Province (No. 2023A1515011564), and National Natural Science Foundation of China (No. 91959127; No. 81971631).

ObjectivesThe impact of blood pressure (BP) control and its timing on left ventricular (LV) structure and function remains unclear. The present study was to evaluate whether BP control correlated with conventional LV geometry and function indexes or global longitudinal strain (GLS) progression, and when echocardiographic changes would occur in essential hypertension.Methods and resultsA total of 62 participants (mean age 55.2 ± 11.5, male 71.0%) with uncontrolled hypertension were enrolled in the longitudinal study. Patients were followed up at the 6-month and 18-month, when echocardiographic measurements were performed and BP control was evaluated during the follow up period. At the 6- and 18-month examination, we divided the hypertensive patients into two groups as BP controlled and uncontrolled group. Patients with BP uncontrolled (n = 33) had higher LV mass index (P = 0.02), higher left atrial volume index (P = 0.01), worse GLS (P = 0.005) and GLS changes (P = 0.003) compared with controlled BP (n = 29) at the 6-month follow-up examination. Patients with uncontrolled BP (n = 25) had higher LV mass index (P = 0.001), higher LV mass index changes (P = 0.01), higher relative wall thickness (P = 0.01), higher E/e′ (P = 0.046), worse GLS (P = 0.02) and GLS changes (P = 0.02) compared to BP controlled group (n = 24) at the 18-month follow-up examination. GLS changes were associated with BP control (β = 0.370, P = 0.004 at the 6-month examination and β = 0.324, P = 0.02 at the 18-month examination, respectively) in stepwise multivariate regression analysis. LV mass index changes was corelated with systolic BP (β = 0.426, P = 0.003) at the 18-month follow-up examination in stepwise multivariate regression analysis. Neither was GLS changes nor LV mass index changes were related to antihypertensive medication class, including combination therapy in 6- or 18-month follow up examination.ConclusionsOur findings offer new clinical evidence on the association of BP control with echocardiographic changes in hypertensive patients, and, in particular, support the view that GLS progression was earlier and subtler than conventional LV geometry and function parameters. GLS changes were significant between BP controlled and uncontrolled patients even in 6-month follow-up period.

This study presents an electrolysis system utilizing a novel self-circulation process of sulfate (SO42−) and persulfate (S2O82−) ions based on a boron-doped diamond (BDD) anode and an activated carbon fiber (ACF) cathode, which is designed to enable electrochemical remediation of environmental contaminants with reduced use of chemical reagents and minimized residues. The production of S2O82− and hydrogen peroxide (H2O2) on the BDD anode and ACF cathode, respectively, is identified as the source of active radicals for the contaminant degradation. The initiator, sulfate, is identified by comparing the degradation efficiency in NaSO4 and NaNO3 electrolytes. Quenching experiments and electron paramagnetic resonance (EPR) spectroscopy confirmed that the SO4−· and ·OH generated on the ACF cathode are the main reactive radicals. A comparison of the degradation efficiency and the generated S2O82−/H2O2 of the divided/undivided electrolysis system is used to demonstrate the superiority of the synergistic effect between the BDD anode and ACF cathode. This work provides evidence of the effectiveness of the philosophy of “catalysis in lieu of supplementary chemical agents” and sheds light on the mechanism of the generation and transmission of reactive species in the BDD and ACF electrolysis system, thereby offering new perspectives for the design and optimization of electrolysis systems.

This study presents the method of fixed-photon-energy double-imaging photoelectron photoion coincidence (i2PEPICO) utilized to investigate the dissociation of state-selected ions. Vacuum ultraviolet (VUV) synchrotron radiation at one fixed photon energy of hν = 21.2 eV, the He(I) atomic resonance energy, is employed as a light source to ionize molecules. Various dynamic information including time-of-flight (TOF) mass spectra, mass-selected photoelectron spectra (PES), and electron and ion kinetic energy correlation diagrams corresponding to each mass are obtained efficiently with the multiplexed capabilities of i2PEPICO, thereby revealing the detailed dissociation mechanisms of ions. As representative examples, dissociation of state-selected O2+ ions prepared in the b4∑g− and B2∑g− electronic states and CH3F+ ions in the X2E, A2A1, and B2E states were selected and investigated.

Abstract Cytarabine (Ara-C) is the first-line drug for the treatment of acute myelogenous leukemia (AML). However, resistance eventually develops, decreasing the efficacy of Ara-C in AML patients. The expression of SAMHD1, a deoxynucleoside triphosphate (dNTP) triphosphohydrolase, has been reported to be elevated in Ara-C-resistant AML patients and to play a crucial role in mediating Ara-C resistance in AML. However, the mechanism by which SAMHD1 is upregulated in resistant AML remains unknown. In this study, NONO interacted with and stabilized SAMHD1 by inhibiting DCAF1-mediated ubiquitination/degradation of SAMHD1. Overexpression of NONO increased SAMHD1 expression and reduced the sensitivity of AML cells to Ara-C, and downregulation of NONO had the opposite effects. In addition, the DNA-damaging agents DDP and adriamycin (ADM) reduced NONO/SAMHD1 expression and sensitized AML cells to Ara-C. More importantly, NONO was upregulated in Ara-C-resistant AML cells, resulting in increased SAMHD1 expression in resistant AML cells, and DDP and ADM treatment resensitized resistant AML cells to Ara-C. This study revealed the mechanism by which SAMHD1 is upregulated in Ara-C-resistant AML cells and provided novel therapeutic strategies for Ara-C-resistant AML.

BackgroundEstrogen/estrogen receptor signaling influences the tumor microenvironment and affects the efficacy of immunotherapy in some tumors, including melanoma. This study aimed to construct an estrogen response-related gene signature for predicting response to immunotherapy in melanoma.MethodsRNA sequencing data of 4 immunotherapy-treated melanoma datasets and TCGA melanoma was obtained from open access repository. Differential expression analysis and pathway analysis were performed between immunotherapy responders and non-responders. Using dataset GSE91061 as the training group, a multivariate logistic regression model was built from estrogen response-related differential expression genes to predict the response to immunotherapy. The other 3 datasets of immunotherapy-treated melanoma were used as the validation group. The correlation was also examined between the prediction score from the model and immune cell infiltration estimated by xCell in the immunotherapy-treated and TCGA melanoma cases.Results“Hallmark Estrogen Response Late” was significantly downregulated in immunotherapy responders. 11 estrogen response-related genes were significantly differentially expressed between immunotherapy responders and non-responders, and were included in the multivariate logistic regression model. The AUC was 0.888 in the training group and 0.654–0.720 in the validation group. A higher 11-gene signature score was significantly correlated to increased infiltration of CD8+ T cells (rho=0.32, p=0.02). TCGA melanoma with a high signature score showed a significantly higher proportion of immune-enriched/fibrotic and immune-enriched/non-fibrotic microenvironment subtypes (p

Abstract Background Osteosarcoma (OS) is a tumour with a high malignancy level and a poor prognosis. First-line chemotherapy for OS has not been improved for many decades. Bromodomain and extraterminal domain (BET) and histone deacetylases (HDACs) regulate histone acetylation in tandem, and BET and HDACs have emerged as potential cancer therapeutic targets. Methods Cell proliferation, migration, invasion, colony formation, and sphere-forming assays were performed with the two inhibitors alone or in combination to evaluate their suppressive effect on the malignant properties of OS cells. Apoptosis and the cell cycle profile were measured by flow cytometry. The synergistic inhibitory effect of OTX015/WT-161 on tumours was also examined in a nude mouse xenograft model. Results The combined therapy of OTX015/WT-161 synergistically inhibited growth, migration, and invasion and induced apoptosis, resulting in G1/S arrest of OS cells. Additionally, OTX015/WT-161 inhibited the self-renewal ability of OS stem cells (OSCs) in a synergistic manner. Further mechanistic exploration revealed that the synergistic downregulation of β-catenin by OTX015-mediated suppression of FZD2 and WT-161-mediated upregulation of PTEN may be critical for the synergistic effect. Finally, the results of an in vivo assay showed that tumour xenografts were significantly decreased after treatment with the OTX015/WT-161 combination compared with OTX015 or WT-161 alone. Conclusions Our findings in this study demonstrated that OTX015 and WT-161 had synergistic anticancer efficacy against OS, and their combination might be a promising therapeutic strategy for OS.

In order to solve the difficulties and challenges in the implementation of the original blood distribution and collection regulations caused by the expansion of hospital area, the extension of blood transfer time, the changeability of blood transfer environment, and the strain of personnel due to the increase of workload, as well as to ensure the accuracy of the information throughout blood remote verification and distribution and the safety of clinical blood transfusion, , Shanghai experts related to clinical transfusion and blood management had made a systematic study on the applicable scope and management rules of remote verification of blood distribution and collection, and formulated this Expert Consensus combined with the development status of digital, intelligent and remote communication technologies, so as to provide corresponding guidance for clinical medical institutions in line with the changes in reality.

Abstract High power‐generation efficiency can be achieved by optimising the shape of the claw pole used as automobile generators. The working process of the stator and rotor in the claw pole generator was simulated using the finite‐element method. First, one of the eight typical claw pole types commonly used in industry was selected. Then, orthogonal optimisation was performed based on the simulation results, yielding an optimal claw shape design. To examine the adaptability of the designed claw pole to shape change, the non‐destructive test for evaluating the magnetic properties of claw pole (NDTEM) was employed. Finally, a claw pole with an optimal shape was forged, and its magnetic induction intensity was assessed using the NDTEM. The results indicated that compared with the unoptimised claw pole, the magnetic induction intensity of the optimised claw pole increased by a maximum of 8.11% and its weight reduced by 4.86%. This optimisation effectively improved the efficiency of power generation and achieved the lightweight of the claw pole.

BackgroundAging is usually accompanied by functional declines of the immune system, especially in T-cell responses. However, little is known about ways to alleviate this.MethodsHere, 37 middle-aged healthy participants were recruited, among which 32 were intravenously administrated with expanded NK cells and 5 with normal saline. Then, we monitored changes of peripheral senescent and exhausted T cells within 4 weeks after infusion by flow cytometry, as well as serum levels of senescence-associated secretory phenotype (SASP)-related factors. In vitro co-culture assays were performed to study NK-mediated cytotoxic activity against senescent or exhausted T cells. Functional and phenotypic alteration of NK cells before and after expansion was finally characterized.ResultsAfter NK cell infusion, senescent CD28-, CD57+, CD28-CD57+, and CD28-KLRG1+ CD4+ and CD8+ T-cell populations decreased significantly, so did PD-1+ and TIM-3+ T cells. These changes were continuously observed for 4 weeks. Nevertheless, no significant changes were observed in the normal saline group. Moreover, SASP-related factors including IL-6, IL-8, IL-1α, IL-17, MIP-1α, MIP-1β, and MMP1 were significantly decreased after NK cell infusion. Further co-culture assays showed that expanded NK cells specifically and dramatically eliminated senescent CD4+ T cells other than CD28+CD4+ T cells. They also showed improved cytotoxic activity, with different expression patterns of activating and inhibitory receptors including NKG2C, NKG2A, KLRG1, LAG3, CD57, and TIM3.ConclusionOur findings imply that T-cell senescence and exhaustion is a reversible process in healthy individuals, and autologous NK cell administration can be introduced to alleviate the aging.Clinical Trial RegistrationClinicalTrials.gov, ChiCTR-OOh-17011878.

Background and AimsMicrovascular invasion (MVI) is a well-known risk factor for poor prognosis in hepatocellular carcinoma (HCC). This study aimed to develop a deep convolutional neural network (DCNN) model based on contrast-enhanced ultrasound (CEUS) to predict MVI, and thus to predict prognosis in patients with HCC.MethodsA total of 436 patients with surgically resected HCC who underwent preoperative CEUS were retrospectively enrolled. Patients were divided into training (n = 301), validation (n = 102), and test (n = 33) sets. A clinical model (Clinical model), a CEUS video-based DCNN model (CEUS-DCNN model), and a fusion model based on CEUS video and clinical variables (CECL-DCNN model) were built to predict MVI. Survival analysis was used to evaluate the clinical performance of the predicted MVI.ResultsCompared with the Clinical model, the CEUS-DCNN model exhibited similar sensitivity, but higher specificity (71.4% vs. 38.1%, p = 0.03) in the test group. The CECL-DCNN model showed significantly higher specificity (81.0% vs. 38.1%, p = 0.005) and accuracy (78.8% vs. 51.5%, p = 0.009) than the Clinical model, with an AUC of 0.865. The Clinical predicted MVI could not significantly distinguish OS or RFS (both p > 0.05), while the CEUS-DCNN predicted MVI could only predict the earlier recurrence (hazard ratio [HR] with 95% confidence interval [CI 2.92 [1.1–7.75], p = 0.024). However, the CECL-DCNN predicted MVI was a significant prognostic factor for both OS (HR with 95% CI: 6.03 [1.7–21.39], p = 0.009) and RFS (HR with 95% CI: 3.3 [1.23–8.91], p = 0.011) in the test group.ConclusionsThe proposed CECL-DCNN model based on preoperative CEUS video can serve as a noninvasive tool to predict MVI status in HCC, thereby predicting poor prognosis.

Abstract Systolic blood pressure (SBP) and resting pulse rate (RPR) have been linked to mortality and cardiovascular events in younger population. Till now, no studies simultaneously investigate the non‐linear association of SBP and RPR with all‐cause and cardiovascular mortality among population aged 80 and older. Data of 2828 eligible participants were selected from electronic health records linked attended automated office blood pressure measurement system. The dose‐response relationship between the SBP, RPR, and the risk of all‐cause and cardiovascular mortality was analyzed by Cox model with restricted cubic splines. During the 3.6‐year follow‐up, 442 deaths occurred. Comparing with the optimal SBP (117‐145 mmHg), the lower (HR: 1.39, 95% CI: 1.07‐1.81) and higher SBP (HR: 1.34, 95% CI: 1.08‐1.65) were significantly associated with an increasing risk of all‐cause mortality. The higher SBP (>144 mmHg) was associated with cardiovascular mortality, with the HR (95% CI) as 1.51 (1.07‐2.12). The faster RPR showed the higher risk of all‐cause (HR: 1.36, 95% CI: 1.05‐1.76) and cardiovascular (HR: 1.51, 95% CI: 1.07‐2.13) mortality. We found both higher SBP and faster RPR were independently associated with all‐cause and cardiovascular mortality, and lower SBP was only associated with the increased risk of all‐cause mortality in oldest old community‐dwelling Chinese population. Our results demonstrate the prognostic importance of both SBP and RPR in the elderly.

This paper presents the data of chemical composition of the particles from OH oxidation reaction of 1,3,5-trimethylbenzene (1,3,5-TMB). The particle-phase compositions are measured on-line by using a vacuum ultraviolet (VUV) photoionization aerosol mass spectrometer. The assignments of the major peaks of photoionization mass spectrum, as well as their molecular structures, are presented. The optimized structures of the reactants, intermediates and transition states involved in the reaction of the bicyclic peroxy radical with HO2 are shown. The reaction routes of the OH-initiated oxidation of the deuterated 1,3,5-TMB sample are also calculated and displayed for comparison. The data presented here is related to the paper “Direct observation of the particle-phase bicyclic products from OH-initiated oxidation of 1,3,5-trimethylbenzene under NOx-free conditions” by Lin et al. (2022).

BackgroundAdrenal venous sampling (AVS) is recognized as the gold standard for subtyping primary aldosteronism (PA), but its invasive nature and technical challenges limit its availability. A recent study reported that sodium chloride cotransporter (NCC) in urinary extracellular vesicles (uEVs) is a promising marker for assessing the biological activity of aldosterone and can be treated as a potential biomarker of PA. The current study was conducted to verify the hypothesis that the expression of NCC and its phosphorylated form (pNCC) in uEVs are different in various subtypes and genotypes of PA and can be used to select AVS candidates.MethodsA total of 50 patients with PA were enrolled in the study. Urinary extracellular vesicles (uEVs) were isolated from spot urine samples using ultracentrifugation. NCC and pNCC expressions were tested in patients diagnosed with PA who underwent AVS. Sanger sequencing of KCNJ5 was performed on DNA extracted from adrenal adenoma.ResultspNCC (1.89 folds, P

Mixed-halide perovskites are of interest for photovoltaic devices, but light-induced halide segregation obstructs bandgap tuning and is not fully understood. Here the authors study the effects of strain and iodide/bromide ratio on light-induced halide segregation in mixed-halide perovskites.

Online analysis of chemical composition of cigarette smoke of a heated tobacco product (HTP) was performed by using a home-made vacuum ultraviolet (VUV) lamp-based photoionization time-of-flight (TOF) mass spectrometer. A capillary inlet and an aerodynamic lens were utilized to sample the gas- and particulate-phase of the HTP smoke, without dilution and pretreatment, which can be switched from each other within minutes. A thermal desorption unit was installed to vaporize the particulate-phase into gas and its vaporization temperature was determined, based on an equilibrium between the evaporation efficiency and the thermal decomposition of organic compounds. Then these species were softly ionized by VUV photons and their ions were measured by a reflectron TOF mass analyzer. Meanwhile, the puff-by-puff resolved size distributions of the HTP smoke were probed with a commercial scanning mobility particle sizers (SMPS). The mean diameters of particles firstly increase with the puff number, mainly located in the range of 200 – 300 nm, and then approached a steady state. This method was validated to measure the physical-chemical characteristics of the HTP cigarette smoke. • A capillary inlet and an aerodynamic lens were utilized to sample the gas- and particulate-phase of the HTP smoke. • Chemical composition of the HTP smoke was measured by using a compact VUV photoionization mass spectrometer. • The particle size distribution of the HTP smoke without dilution was measured online.

Biological control of postharvest diseases has been proven to be an effective alternative to chemical control. As an environmentally friendly biocontrol agent, Bacillus subtilis has been widely applied. This study explores its application in kiwifruit soft rot and reveals the corresponding mechanisms. Treatment with cell-free supernatant (CFS) of Bacillus subtilis BS-1 significantly inhibits the mycelial growth of the pathogen Botryosphaeria dothidea and attenuates the pathogenicity on kiwifruit in a concentration-dependent manner. In particular, mycelial growth diameter was only 21% of the control after 3 days of treatment with 5% CFS. CFS caused swelling and breakage of the hyphae of B. dothidea observed by scanning electron microscopy, resulting in the leakage of nucleic acid and soluble protein and the loss of ergosterol content. Further analysis demonstrated that CFS significantly induces the expression of Nox genes associated with reactive oxygen species (ROS) production by 1.9–2.7-fold, leading to a considerable accumulation of ROS in cells and causing mycelial cell death. Our findings demonstrate that the biocontrol effect of B. subtilis BS-1 CFS on B. dothidea is realized by inducing oxidative damage to the mycelia cell.

Abstract The magnetic properties of the claw pole have a direct effect on the output power of a generator. Many methods can be used to measure these magnetic properties, each with its own advantages, but an important shortcoming is that all are destructive. In this study, a new non-destructive method to measure the magnetic properties of claw pole was proposed and a corresponding testing set-up was designed. A finite-element model was constructed to simulate the measurement process. Results proved that the measured magnetization-like curves had good agreement with the trend of the input magnetic curves and the effect of the positioning error in the measuring process could be neglected. To further validate the new method, seven types of claw poles of different materials subjected to different heat-treatment processes were forged and tested by both the new method and the conventional ring-sample method. Compared with the latter, the new method showed better consistency, relatively higher accuracy, and much stronger stability of measurement results; however, its sensitivity needs to be improved. The effects of material compositions and heat-treatment parameters on the magnetic properties of the claw pole were briefly analyzed.

Background and aims: Genetic factors play an important role in the cervico-cerebral large-artery atherosclerotic stenosis (LAS), and ATP2B1 gene has been associated with the process of atherosclerosis disorders, such as coronary artery disease and arterial stiffness. But there is little information about the relationship between ATP2B1 gene and atherosclerosis in the intracranial arteries. We hereby investigated the association of common variants in ATP2B1 gene with LAS in asymptomatic Chinese hypertension patients. Methods: The stenosis of intracranial and extracranial arteries were evaluated in 899 subjects through computerized tomography angiography from the aortic arch to the skull base. A total of 11 ATP2B1 common variants were genotyped. Multivariate logistic regression was carried out in a dominant model with confounding factors adjusted. Results: rs17249754-A (OR = 0.43, p = 0.0002) and rs1401982-G (OR = 0.47, p = 0.0007) were associated with decreased susceptibility of concurrent extra and intracranial stenosis even after Bonferroni correction. These two minor alleles were also significantly associated with less stenotic arteries and moderate-to-severe stenosis. Conclusion: rs17249754 and rs1401982 were associated with asymptomatic LAS in stroke-free Chinese hypertension patients and might benefit early recognition of LAS patients in clinical practice.

BackgroundAccurate prediction of recurrence is crucial for personalized treatment in breast cancer, and whether the radiomics features of ultrasound (US) could be used to predict recurrence of breast cancer is still uncertain. Here, we developed a radiomics signature based on preoperative US to predict disease-free survival (DFS) in patients with invasive breast cancer and assess its additional value to the clinicopathological predictors for individualized DFS prediction.MethodsWe identified 620 patients with invasive breast cancer and randomly divided them into the training (n = 372) and validation (n = 248) cohorts. A radiomics signature was constructed using least absolute shrinkage and selection operator (LASSO) Cox regression in the training cohort and validated in the validation cohort. Univariate and multivariate Cox proportional hazards model and Kaplan–Meier survival analysis were used to determine the association of the radiomics signature and clinicopathological variables with DFS. To evaluate the additional value of the radiomics signature for DFS prediction, a radiomics nomogram combining the radiomics signature and clinicopathological predictors was constructed and assessed in terms of discrimination, calibration, reclassification, and clinical usefulness.ResultsThe radiomics signature was significantly associated with DFS, independent of the clinicopathological predictors. The radiomics nomogram performed better than the clinicopathological nomogram (C-index, 0.796 vs. 0.761) and provided better calibration and positive net reclassification improvement (0.147, P = 0.035) in the validation cohort. Decision curve analysis also demonstrated that the radiomics nomogram was clinically useful.ConclusionUS radiomics signature is a potential imaging biomarker for risk stratification of DFS in invasive breast cancer, and US-based radiomics nomogram improved accuracy of DFS prediction.

Objective This was a prospective study to investigate whether progesterone affects sperm activity by regulating the cyclic AMP-protein kinase A (cAMP-PKA) signalling pathway via α/β hydrolase domain-containing protein 2 (ABHD2). Methods Spermatozoa were collected from healthy and infertile men (with oligoasthenospermia or abnormal acrosome; n = 30/group). The expression of and mutations in ABHD2 were detected by quantitative PCR, western blot, and gene sequencing. The expression of ABHD2 in the presence of progesterone was detected in all groups, and cAMP and PKA levels were detected by ELISA in fertile men after treatment with ABHD2 antibody and PKA inhibitor H-89, respectively. Results Expression of ABHD2 mRNA and protein were reduced in spermatozoa from infertile compared with fertile men. Four gene mutation sites were detected in spermatozoa from the infertile groups. Progesterone increased mRNA and protein levels of ABHD2 in healthy spermatozoa but not in spermatozoa from infertile men. The levels of cAMP and PKA were increased by progesterone in healthy spermatozoa, and the progesterone-increased cAMP and PKA were decreased by ABHD2 antibody and H-89, respectively. Conclusion Progesterone regulates the ABHD2-mediated cAMP-PKA signalling pathway in healthy spermatozoa, which provides a new target for clinical diagnosis and treatment of infertility.

Water-based semiconducting polymer nanoparticles are eco-friendly and non-toxic but their performance suffers from the surfactants. Here Xie et al. design an approach to minimize the amount of residual surfactant in these nanoparticles and make high-efficiency and stability solar cells.

Abstract Background Long non-coding RNA (lncRNA) SNHG5 has been found to play an important role in tumors. Nevertheless, the function and mechanism of lncRNA SNHG5 in osteosarcoma (OS) remains unclear. The purpose of this study was to investigate whether lncRNA SNHG5 can regulate the occurrence and development of OS cells. Methods We performed quantitative real time PCR to detect the expression of lncRNA SNHG5 in OS cells. 143B, MG63 (knockdown) and U2OS, U2R (overexpression) cell lines were chosen for the function study of SNHG5. The effect of SNHG5, miR-212-3p, and SGK3 in OS cells was explored by MTT assays, clony formation, flow cytometry, transwell assays, wound healing assays, and cell spreading assays. Quantitative real-time PCR, Western blot analysis and luciferase assays were used to detect the interaction between lncRNA SNHG5 and miR-212-3p. Results In this study, knockdown of lncRNA SNHG5 suppressed the growth and metastasis of OS cells, whereas the overexpression of SNHG5 produced an opposite result. Mechanistically, lncRNA SNHG5 functions as a sponger against miR-212-3p and suppresses the miR-212-3p/SGK3 signaling pathway. Introduction of miR-212-3p mimics or inhibitors reverses SNHG5 overexpression or silences the exerted tumor promoting or suppressing effect. In addition, our results showed that the function of SNHG5 can be rescued by miR-212-3p and can regulate the growth and metastasis of OS cells via SGK3, the downstream target of miR-212-3p. Conclusions In summary, our study demonstrated that lncRNA SNHG5 can regulate the proliferation and metastasis of OS cells through the miR-212-3p/SGK3 axis. This axis may provide a new target for future clinical treatment.

The absolute absorption cross-section of the ethyl peroxy radical C2H5O2 in the Ã←X˜ electronic transition with the peak wavelength at 7596 cm−1 has been determined by the method of dual wavelengths time resolved continuous wave cavity ring down spectroscopy. C2H5O2 radicals were generated from pulsed 351 nm photolysis of C2H6/Cl2 mixture in presence of 100 Torr O2 at T = 295 K. C2H5O2 radicals were detected on one of the CRDS paths. Two methods have been applied for the determination of the C2H5O2 absorption cross-section: (i) based on Cl-atoms being converted alternatively to either C2H5O2 by adding C2H6 or to hydro peroxy radicals, HO2, by adding CH3OH to the mixture, whereby HO2 was reliably quantified on the second CRDS path in the 2ν1 vibrational overtone at 6638.2 cm−1 (ii) based on the reaction of C2H5O2 with HO2, measured under either excess HO2 or under excess C2H5O2 concentration. Both methods lead to the same peak absorption cross-section for C2H5O2 at 7596 cm−1 of σ = (1.0 ± 0.2) × 10−20 cm2. The rate constant for the cross reaction between of C2H5O2 and HO2 has been measured to be (6.2 ± 1.5) × 10−12 cm3 molecule−1 s−1.

Abstract Background Clinical ovulation induction induces blood estrogen (E2) in excess of physiological levels, which can hinder uterine receptivity. In contrast, progesterone produces the opposite clinical effect, suggesting that it might be capable of recovering the lost receptivity resulting from exposure to high estrogen levels. Integrins are the most widely used biological markers for monitoring uterine conditions. We studied progesterone-induced changes in integrin β expression patterns as biomarkers for changes in uterine receptivity in response to increased estrogen levels. Methods Endometrial biopsy samples from patients were screened for their estrogen (E2) and progesterone (P4) content and expressing levels of integrin β1 and β3. Uterine receptivity was evaluated using human endometrial adenocarcinoma cells in an embryo attachment model. The respective and concatenated effects of embryo attachment and changes in the integrin β1 and β3 expression patterns on the adenocarcinoma cell plasma membranes in response to 100 nM concentrations of E2 and P4 were evaluated. Results Increased blood E2 concentrations were associated with significantly decreased the levels of integrin β3 expression in uterine biopsy samples. In vitro experiments revealed that a 100 nM E2 concentration inhibited the distribution of integrin β3 on the plasma membranes of human endometrial adenocarcinoma cells used in the embryo attachment model, and resulted in decreased rates of embryo attachment. In contrast, P4 enhanced the expression of integrin β1 and promoted its distribution on the plasma membranes. Furthermore, P4 recovered the embryo attachment efficiency that was lost by exposure to 100 nM E2. Conclusions Blood E2 and P4 levels and integrin β3 and β1 expression levels in uterine biopsy samples should be considered as biomarkers for evaluating uterine receptivity and determining the optimal time for embryo transfer. Trial registration Trial number: ChiCTR-TRC-13003777; Name of registry: Chinese Clinical Trial Registry; Date of registration: 4 September 2013; Date of enrollment of the first study participant: 15 October 2013

A Highway Intelligent Space System (HISS) is proposed to study vehicle environment perception in this paper. The nature of HISS is that a space sensors system using laser, ultrasonic or radar sensors are installed in a highway environment and communication technology is used to realize the information exchange between the HISS server and vehicles, which provides vehicles with the surrounding road information. Considering the high-speed feature of vehicles on highways, when vehicles will be passing a road ahead that is prone to accidents, the vehicle driving state should be predicted to ensure drivers have road environment perception information in advance, thereby ensuring vehicle driving safety and stability. In order to verify the accuracy and feasibility of the HISS, a traditional vehicle-mounted sensor system for environment perception is used to obtain the relative driving state. Furthermore, an inter-vehicle dynamics model is built and model predictive control approach is used to predict the driving state in the following period. Finally, the simulation results shows that using the HISS for environment perception can arrive at the same results detected by a traditional vehicle-mounted sensors system. Meanwhile, we can further draw the conclusion that using HISS to realize vehicle environment perception can ensure system stability, thereby demonstrating the method’s feasibility.

Intracranial arterial stenosis (ICAS) is a common cause of ischemic stroke in Asians, whereas whites tend to have more extracranial lesions. Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been associated with ischemic stroke by a large amount of work. However, there are few studies focusing on the relationship of Lp-PLA2 and asymptomatic ICAS or extracranial arterial stenosis (ECAS). Wehereby sought to explore the relationship of Lp-PLA2 and ICAS, ECAS and concurrent stenosis in stroke-free hypertensive patients in Chinese population.All the subjects were evaluated for the presence and severity of ICAS and ECAS through computerized tomographic angiography (CTA) covered the whole brain down to the level of aortic arch. Lp-PLA2 mass was measured by enzyme linked immunoassay. The association of Lp-PLA2 and vascular stenosis was analyzed through multivariate logistic regression.Among 414 participants, 163 (39.4%) had no ICAS or ECAS, 63 (15.2%) had ECAS only, 111 (26.8%) had ICAS only and 77 (18.6%) had concurrent extraintracranial stenosis. Lp-PLA2 mass was significantly associated with isolated ICAS (OR: 2.3; 95% CI: 1.14-4.64), and concurrent stenosis (OR: 3.93; 95% CI: 1.62-9.51), but was not related to isolated ECAS (OR: 1.54; 95% CI: 0.68-3.48). Lp-PLA2 mass was also associated with moderate to severe ICAS no matter how was the ECAS. Moreover, patients with higher Lp-PLA2 mass showed more sever ICAS and had more intracranial arterial lesions.This study revealed the association of Lp-PLA2 mass with ICAS in stroke-free hypertensive patients in Chinese population. The further long-term cohort study was warranted to elucidate the concrete effect of Lp-PLA2 on the asymptomatic ICAS.

BACKGROUND: Most studies have suggested that elevated body mass index (BMI) was associated with the risk of death from all cause and from specific causes. However, there was little evidence illustrating the effect of BMI on the mortality in elderly hypertensive patients in Chinese population. METHODS: The information of 10,957 hypertensive patients at baseline not less than 60 years were from Xinzhuang, a town in Minhang district of Shanghai, was extracted from the Electronic Health Record (EHR) system. All study participants were divided into eight categories of baseline BMI (with cut-points at 18, 20, 22, 24, 26, 28 and 30 kg/m(2)). Relative hazard ratio of death from all cause, cardiovascular and non-cardiovascular cause by baseline BMI groups were calculated, standardized for sex, age, smoking, drinking, physical activity, systolic blood pressure, history of cardiovascular disorders, serum lipid disturbance, diabetes mellitus and antihypertensive drug treatment. RESULTS: DURING FOLLOW UP (MEDIAN: 3.7 years), 561 deaths occurred. Underweight (BMI

Epigenetic modification generally refers to phenotypic changes by a mechanism other than changes in DNA sequence and plays a significant role in developmental processes. In this study, we found that overexpression of one alternatively spliced tomato DDB1 transcript, DDB1(F) that is prevalently present in all tested tissues, resulted in reduction of organ size. Transgenic plants constitutively expressing the DDB1(F) from a strong cauliflower mosaic virus (CaMV) 35S promoter displayed moderately reduced size in vegetative organs (leaves and stems) and radically decreased size in reproductive organs (flowers, seeds and fruits), in which several genes encoding negative regulators for cell division were upregulated. Significantly, reduction of organ size conferred by overexpression of DDB1(F) transgene appears not to segregate in the subsequent generations, suggesting the phenotypic alternations are manipulated in an epigenetic manner and can be transmitted over generations. This notion was further substantiated by analysis of DNA methylation level at the SlWEE1 gene (encoding a negative regulator of cell division), revealing a correlation between less methylation in the promoter region and elevated expression level of this gene. Thus, our results suggest DDB1 plays an important role in regulation of the epigenetic state of genes involved in organogenesis, despite the underlying mechanism remains to be elucidated.