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It has been a common method to improve the mechanical properties of metals by manipulating their microstructures via static recrystallization, i.e., through heat treatment. Therefore, the knowledge of recrystallization and grain growth is critical to the success of the technique. In the present work, by using in-situ high temperature EBSD, the mechanisms that control recrystallization and grain growth of an extruded pure Mg were studied. The experimental results revealed that the grains of priority for dynamic recrystallization exhibit fading competitiveness under static recrystallization. It is also found that grain boundary movement or grain growth is likely to show an inverse energy gradient effect, i.e., low energy grains tend to swallow or grow into high energy grains, and grain boundaries of close to 30° exhibit superior growth advantage to others. Another finding is that {10–12} tensile twin boundaries are sites of hardly observed for recrystallization, and are finally swallowed by adjacent recrystallized grains. The above findings may give comprehensive insights of static recrystallization and grain growth of Mg, and may guide the design of advanced materials processing in microstructural engineering.

BackgroundSteroid-resistant (SR) lower gastrointestinal (LGI) tract graft-versus-host disease (GVHD) is the predominant cause of morbidity and mortality from GVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The role of vedolizumab in the treatment of SR-LGI acute GVHD (aGVHD) remains uncertain. We aimed to assess the efficacy and safety of vedolizumab combined with basiliximab as second-line therapy for SR-LGI-aGVHD.MethodsThis study aimed to explore the efficacy of vedolizumab combined with basiliximab for SR-LGI-aGVHD. The primary endpoint was the overall response (OR) on day 28. Secondary and safety endpoints included durable OR at day 56, overall survival (OS), chronic GVHD (cGVHD), non-relapse mortality (NRM), failure-free survival (FFS), and adverse events.ResultsTwenty-eight patients with SR-LGI-aGVHD were included. The median time to start of combination therapy after SR-LGI-aGVHD diagnosis was 7 (range, 4–16) days. The overall response rate (ORR) at 28 days was 75.0% (95% CI: 54.8%–88.6%), and 18 achieved a complete response (CR) (64.3%, 95% CI: 44.1%–80.7%). The durable OR at day 56 was 64.3% (95% CI: 44.1%–80.7%). The 100-day, 6-month, and 12-month OS rates for the entire cohort of patients were 60.7% (95% CI: 45.1%–81.8%), 60.7% (95% CI: 45.1%–81.8%), and 47.6% (95% CI: 31.4%–72.1%), respectively. The median failure-free survival was 276 days; (95% CI: 50–not evaluable) 12-month NRM was 42.9% (95% CI: 24.1%–60.3%). The 1-year cumulative incidence of cGVHD was 35.7%. Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections. Nine (32.1%) patients developed cytomegalovirus (CMV) reactivation complicated with bacterial infections (25.0%, CMV infection; 7.1%, CMV viremia). Epstein–Barr virus (EBV) reactivation occurred in five patients (17.9%, 95% CI: 6.8%–37.6%). Only three patients (10.7%, 95% CI: 2.8%–29.4%) in our study developed pseudomembranous colitis.ConclusionsVedolizumab plus basiliximab demonstrated efficacy in severe SR-LGI-aGVHD and was well-tolerated. Vedolizumab plus basiliximab may be considered a potential treatment option for patients with LGI-aGVHD.

Colorectal cancer (CRC) is one of the most common malignant tumors recorded worldwide. This condition has high morbidity and mortality and seriously endangers people's health. Traditional diagnostic models fail to meet people's current needs for real-time monitoring of tumors. Compared with traditional detection methods, ctDNA detection is not only noninvasive but can also attain real-time detection of comprehensive genomic information of tumors. The advancement of detection technology has gradually highlighted the potential of ctDNA detection in the clinical treatment of CRC. This article reviews the advancements on the clinical application of ctDNA in early screening, minimal residual disease detection, and guidance on individualized treatment of CRC patients.

Introduction: Facial nerve injury significantly impacts both the physical and psychological] wellbeing of patients. Despite advancements, there are still limitations associated with autografts transplantation. Consequently, there is an urgent need for effective artificial grafts to address these limitations and repair injuries. Recent years have witnessed the recognition of the beneficial effects of chitosan (CS) and graphene in the realm of nerve repair. Dental pulp stem cells (DPSCs) hold great promise due to their high proliferative and multi-directional differentiation capabilities.Methods: In this study, Graphene/CS (G/CST) composite tubes were synthesized and their physical, chemical and biological properties were evaluated, then DPSCs were employed as seed cells and G/CST as a scaffold to investigate their combined effect on promoting facial nerve injury repair.Results and Disscussion: The experimental results indicate that G/CST possesses favorable physical and chemical properties, along with good cyto-compatibility. making it suitable for repairing facial nerve transection injuries. Furthermore, the synergistic application of G/CST and DPSCs significantly enhanced the repair process for a 10 mm facial nerve defect in rabbits, highlighting the efficacy of graphene as a reinforcement material and DPSCs as a functional material in facial nerve injury repair. This approach offers an effective treatment strategy and introduces a novel concept for clinically managing facial nerve injuries.

Purpose Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is the primary cause of death in patients with IPF, characterised by diffuse, bilateral ground-glass opacification on high-resolution CT (HRCT). This study proposes a three-dimensional (3D)-based deep learning algorithm for classifying AE-IPF using HRCT images.Materials and methods A novel 3D-based deep learning algorithm, SlowFast, was developed by applying a database of 306 HRCT scans obtained from two centres. The scans were divided into four separate subsets (training set, n=105; internal validation set, n=26; temporal test set 1, n=79; and geographical test set 2, n=96). The final training data set consisted of 1050 samples with 33 600 images for algorithm training. Algorithm performance was evaluated using accuracy, sensitivity, specificity, positive predictive value, negative predictive value, receiver operating characteristic (ROC) curve and weighted κ coefficient.Results The accuracy of the algorithm in classifying AE-IPF on the test sets 1 and 2 was 93.9% and 86.5%, respectively. Interobserver agreements between the algorithm and the majority opinion of the radiologists were good (κw=0.90 for test set 1 and κw=0.73 for test set 2, respectively). The ROC accuracy of the algorithm for classifying AE-IPF on the test sets 1 and 2 was 0.96 and 0.92, respectively. The algorithm performance was superior to visual analysis in accurately diagnosing radiological findings. Furthermore, the algorithm’s categorisation was a significant predictor of IPF progression.Conclusions The deep learning algorithm provides high auxiliary diagnostic efficiency in patients with AE-IPF and may serve as a useful clinical aid for diagnosis.

Abstract Background It remains unclear how the condition of glucose metabolism during pregnancy affects fetal outcomes. This study aimed to investigate the associations of gestational diabetes mellitus (GDM) and elevated glucose levels at each time point during oral glucose tolerance test (OGTT) with congenital heart disease (CHD) risk in offspring. Methods We conducted a retrospective cohort study of mothers with singleton pregnancies of 20 weeks or more registered at Maternal and Child Health Centers in Fujian Province, China. The OGTT results and offspring CHD occurrence were collected. We used logistic regression to analyse the association between elevated blood glucose at each time point during OGTT and CHD. Results A total of 71,703 normal and 533 CHD fetuses were included. Compared to the corresponding normal group, women with GDM, elevated blood glucose at different time points in OGTT (0 h ≥ 5.1 mmol/L, 1 h ≥ 10 mmol/L, and 2 h ≥ 8.5 mmol/L) showed an increased risk of CHD in offspring (adjusted OR = 1.41, 1.36, 1.37, and 1.41, all P

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive scarring interstitial lung disease with an unknown cause. Some patients may experience acute exacerbations (AE), which result in severe lung damage visible on imaging or through examination of tissue samples, often leading to high mortality rates. However, the etiology and pathogenesis of AE-IPF remain unclear. AE-IPF patients exhibit diffuse lung damage, apoptosis of type II alveolar epithelial cells, and an excessive inflammatory response. Establishing a reliable animal model of AE is critical for investigating the pathogenesis. Recent studies have reported a variety of animal models for AE-IPF, each with its own advantages and disadvantages. These models are usually established in mice with bleomycin-induced pulmonary fibrosis, using viruses, bacteria, small peptides, or specific drugs. In this review, we present an overview of different AE models, hoping to provide a useful resource for exploring the mechanisms and targeted therapies for AE-IPF.

IntroductionIdiopathic pulmonary fibrosis (IPF) is characterized by progressive lung dysfunction due to excessive collagen production and tissue scarring. Despite recent advancements, the molecular mechanisms remain unclear.MethodsRNA sequencing identified 475 differentially expressed genes (DEGs) in the TGF-β1-induced primary lung fibrosis model. Gene expression chips GSE101286 and GSE110147 from NCBI gene expression omnibus (GEO) database were analyzed using GEO2R, revealing 94 DEGs in IPF lung tissue samples. The gene ontology (GO) and pathway enrichment, Protein-protein interaction (PPI) network construction, and Maximal Clique Centrality (MCC) scoring were performed. Experimental validation included RT-qPCR, Immunohistochemistry (IHC), and Western Blot, with siRNA used for gene knockdown. A co-expression network was constructed by GeneMANIA.ResultsGO enrichment highlighted significant enrichment of DEGs in TGF-β cellular response, connective tissue development, extracellular matrix components, and signaling pathways such as the AGE-RAGE signaling pathway and ECM-receptor interaction. PPI network analysis identified hub genes, including FN1, COL1A1, POSTN, KIF11, and ECT2. CALD1 (Caldesmon 1), CDH2 (Cadherin 2), and POSTN (Periostin) were identified as dysregulated hub genes in both the RNA sequencing and GEO datasets. Validation experiments confirmed the upregulation of CALD1, CDH2, and POSTN in TGF-β1-treated fibroblasts and IPF lung tissue samples. IHC experiments probed tissue-level expression patterns of these three molecules. Knockdown of CALD1, CDH2, and POSTN attenuated the expression of fibrotic markers (collagen I and α-SMA) in response to TGF-β1 stimulation in primary fibroblasts. Co-expression analysis revealed interactions between hub genes and predicted genes involved in actin cytoskeleton regulation and cell-cell junction organization.ConclusionsCALD1, CDH2, and POSTN, identified as potential contributors to pulmonary fibrosis, present promising therapeutic targets for IPF patients.

Yun-E Xu,1,* Di-Shu Ao,1,* Xin Sun,1 Wei Chen,2 Xue Luo,1 Can Zhao,1 Sheng-Yu Wang,1 Hong Song1 1Department of Microbiology, School of Basic Medical Sciences, Zunyi Medical University, Zunyi, 563000, People’s Republic of China; 2Department of Hepatobiliary Surgery, Third Affiliated Hospital of Zunyi Medical University (The First People’s Hospital of Zunyi), Zunyi, 563000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Song, Department of Microbiology, School of Basic Medical Sciences, Zunyi Medical University, Zunyi, 563000, People’s Republic of China, Tel +86-18985259977 ; +86-0851-28643582, Email hongsong@zmu.edu.cnPurpose: Hydrogels containing the nano-self-assembling peptide RADA16-I (Nanogels) were utilized as scaffolds to establish airway organoids and an adenovirus-infected model. The results support in vitro adenovirus studies, including isolation and culture, pathogenesis research, and antiviral drug screening.Methods: HSAEC1-KT, HuLEC-5a and HELF cells were cocultured in RADA16-I hydrogel scaffolds to construct an airway organoid model. Adenovirus was used to infect this model for adenovirus-related studies. The morphological characteristics and the proliferation and activity of airway organoids before and after adenovirus infection were evaluated. The expression of the airway organoid marker proteins CC10, KRT8, AQP5, SPC, VIM and CD31 was detected. TEM and qPCR were used to detect adenovirus proliferation in airway organoids.Results: HSAEC1-KT, HuLEC-5a and HELF cells cocultured at 10:7:2 self-assembled into airway organoids and maintained long-term proliferation in a RADA16-I hydrogel 3D culture system. The organoids stably expressed the lumen-forming protein KRT8 and the terminal airway markers AQP5 and SPC. Adenoviruses maintained long-term proliferation in this model.Conclusion: An airway-organoid model of adenovirus infection was constructed in vitro from three human lung-derived cell lines on RADA16-I hydrogels. The model has potential as a novel research tool for adenovirus isolation and culture, pathogenesis research, and antiviral drug screening.Keywords: nano-self-assembling peptide, RADA16-I hydrogels, airway organoids, adenovirus

Abstract The authors previously developed a scaffold‐free tissue‐engineered construct (TEC) from mesenchymal stem cells (MSCs). Although the TEC exhibited even cell distribution and was successfully applied for cartilage repair in animal models, it is unsuitable for relatively large‐scale cartilage defects due to its small size. To solve the problem, the authors recently developed a novel biomaterial, a centrifugally compressed cell‐collagen combined construct (C6) from a mixture of MSCs and atelocollagen, both of which are subjected to centrifugation. The results of the previous study indicated that C6 exhibited high cell viability (70 %) and sufficient cell distribution similar to that of the TEC. In the present study, the morphology and gene expression of C6 were investigated. Histological examination indicated that C6 is six times thicker (approximately 1 mm) than the TEC after a 7‐day culture. The C6 remained unchanged in scale with increased cell density after a 21‐day culture. Scanning electron microscopic observation indicated that C6 exhibited interconnected and porous microstructures, while the TEC had close‐knit microstructures. Reverse transcriptase‐polymerase chain reaction analysis indicated that the expression of sex‐determining region Y‐box 9 and runt‐related transcription factor 2 was significantly higher in C6 than that in TEC.

Objective To compare the clinicopathological characteristics between primary and contralateral cancers in patients with metachronous bilateral breast cancer (MBBC) who carried a BRCA1/2 germline pathogenic variant. Methods A total of 496 BRCA1/2 carriers with primary unilateral breast cancer were included (196 with BRCA1 and 300 with BRCA2). Clinicopathological information of patients was collected, and the median follow-up for the entire cohort was 10.4 years (0.4-20.8 years). Results Among all patients, 31 (15.8%) of the 196 BRCA1 carriers and 49 (16.3%) of the 300 BRCA2 carriers had MBBC, respectively. Among the 31 BRCA1 carriers who developed MBBC, the proportion of triple-negative breast cancer (TNBC) in primary cancer and contralateral cancer was 61.3% and 67.7%, respectively. If the primary cancer of BRCA1-mutated MBBC was TNBC, the probability of the contralateral breast cancer with TNBC was 89.5% (17/19), which was significantly higher than that if the primary cancer was non-TNBC (33.3%, 4/12) (P=0.004). Among the 49 BRCA2 carriers who developed MBBC, the predominant molecular phenotype of the primary and contralateral cancers was HR+ & HER2- (77.6% and 67.3%, respectively; P=0.53). Conclusion Approximately 60% of BRCA1 carriers exhibit TNBC. If a BRCA1 carrier with a TNBC primary breast cancer had an MBBC, the probability of the contralateral breast cancer being TNBC phenotype is almost 89.5%.

Recombinant human TPO (rhTPO) is effective for refractory/relapsed primary immune thrombocytopenia (ITP), but optimal dosing regimen remains elusive. In this multicenter, randomized, controlled trial, a total of 282 adult ITP patients (mean age 47.3 years; 82 men) with a platelet count ≤30 × 109/L or >30 × 109/L with active bleeding randomly received a once daily (QD) subcutaneous injection of 7500 U (n = 64) or 15000 U rhTPO for 14 injections, or 15000 U or 30000 U rhTPO once every other day (QOD) for 7 injections. The primary outcomes included change from baseline in platelet count and total response rate (TRR) on day 14. On day 14, the median increase of platelet count from baseline was the highest in the 15000-U QD group (167.5 × 109/L, interquartile range [IQR] 23.0–295.0 × 109/L), followed by the 30000-U QOD group (57.5 × 109/L, IQR 9.0–190.0 × 109/L) (ANCOVA P

IntroductionBrain glioma segmentation is a critical task for medical diagnosis, monitoring, and treatment planning.DiscussionAlthough deep learning-based fully convolutional neural networks have shown promising results in this field, their unstable segmentation quality remains a major concern. Moreover, they do not consider the unique genomic and basic data of brain glioma patients, which may lead to inaccurate diagnosis and treatment planning.MethodsThis study proposes a new model that overcomes this problem by improving the overall architecture and incorporating an innovative loss function. First, we employed DeepLabv3+ as the overall architecture of the model and RegNet as the image encoder. We designed an attribute encoder module to incorporate the patient’s genomic and basic data and the image depth information into a 2D convolutional neural network, which was combined with the image encoder and atrous spatial pyramid pooling module to form the encoder module for addressing the multimodal fusion problem. In addition, the cross-entropy loss and Dice loss are implemented with linear weighting to solve the problem of sample imbalance. An innovative loss function is proposed to suppress specific size regions, thereby preventing the occurrence of segmentation errors of noise-like regions; hence, higher-stability segmentation results are obtained. Experiments were conducted on the Lower-Grade Glioma Segmentation Dataset, a widely used benchmark dataset for brain tumor segmentation.ResultsThe proposed method achieved a Dice score of 94.36 and an intersection over union score of 91.83, thus outperforming other popular models.

Abstract Background Preeclampsia (PE) is a complication of pregnancy that causes long-term adverse outcomes for the mother and fetus and may even lead to death. Oxidative stress caused by the imbalance of oxidants and antioxidants in the placenta has been considered as one of the key mechanisms of preeclampsia (together with inflammation, etc.), in which the placental mitochondria play an important role. The expression of hypoxia-inducible factor-1 (HIF-1α) and vascular endothelial growth factor (VEGF) is known to be increased in patients with PE. Mitochondrial ferritin (FtMt) is known to protect the mitochondria from oxidative stress, although its specific role in PE remains unclear. Methods We used qRT-PCR and western blotting to detect the expression levels of FtMt, HIF-1α, and VEGF in placental tissues from patients with PE. Human chorionic trophoblast cells were also administered with hypoxia treatment, followed by the detection of cell proliferation, invasion and angiogenic capacity by CCK8, Transwell, and endothelial cell angiogenesis assays; we also detected the expression of HIF-1α and VEGF in these cells. Finally, overexpression or inhibitory FtMt lentiviral vectors, along with negative control vectors, were constructed and transfected into hypoxia-treated human chorionic trophoblast cells; this was followed by analyses of cell function. Results The expression levels of FtMt, HIF-1α and VEGF in the PE group were higher than those in the control group (P

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. NAFLD starts with hepatic lipid accumulation, which may cause inflammation and ultimately lead to fibrosis in the liver. Studies have shown that intestinal microorganisms and a variety of bioactive substances produced by them interact with host hepatocytes through the portal vein, resulting in the occurrence and development of NAFLD. The bidirectional communication between the intestinal tract and the liver is called the gut-liver axis. In this paper, the mechanism of the occurrence and development of NAFLD mediated by the gut-liver axis is elaborated from the perspectives of intestinal microbial composition, intestinal barrier function, intestinal microbial components and intestinal microbial metabolites, as well as the role of nutritional intervention in ameliorating NAFLD by targeting the gut-liver axis. This article reviews the existing knowledge on the mechanisms of the complex interaction between intestinal disorders and NAFLD in order to provide nutritional strategies for the prevention and improvement of NAFLD.

Abstract Background Ibrutinib has revolutionized the treatment of mantle cell lymphoma (MCL). Both ibrutinib monotherapy and ibrutinib‐based combination therapy are important salvage options for patients with relapsed/refractory (R/R) MCL. The real‐world efficacy and safety profile of the two strategies in Chinese patients with R/R MCL remain unclarified. Methods In the present study, data of 121 R/R MCL patients who received either ibrutinib monotherapy (N = 68) or ibrutinib combination therapy (N = 53) in 13 medical centers in China were retrospectively reviewed. Results With a median follow‐up of 20.5 months, the overall response rate was 60.3% versus 84.9% (p = 0.003), complete remission rate was 16.2% versus 43.4% (p

Abstract Background Radiotherapy is an important treatment for patients with stage III/IV non-small cell lung cancer (NSCLC), and due to its high incidence of radiation pneumonitis, it is essential to identify high-risk people as early as possible. The present work investigates the value of the application of different phase data throughout the radiotherapy process in analyzing risk of grade ≥ 2 radiation pneumonitis in stage III/IV NSCLC. Furthermore, the phase data fusion was gradually performed with the radiotherapy timeline to develop a risk assessment model. Methods This study retrospectively collected data from 91 stage III/IV NSCLC cases treated with Volumetric modulated arc therapy (VMAT). Patient data were collected according to the radiotherapy timeline for four phases: clinical characteristics, radiomics features, radiation dosimetry parameters, and hematological indexes during treatment. Risk assessment models for single-phase and stepwise fusion phases were established according to logistic regression. In addition, a nomogram of the final fusion phase model and risk classification system was generated. Receiver operating characteristic (ROC), decision curve, and calibration curve analysis were conducted to internally validate the nomogram to analyze its discrimination. Results Smoking status, PTV and lung radiomics feature, lung and esophageal dosimetry parameters, and platelets at the third week of radiotherapy were independent risk factors for the four single-phase models. The ROC result analysis of the risk assessment models created by stepwise phase fusion were: (area under curve [AUC]: 0.67,95% confidence interval [CI]: 0.52–0.81), (AUC: 0.82,95%CI: 0.70–0.94), (AUC: 0.90,95%CI: 0.80–1.00), and (AUC:0.90,95%CI: 0.80–1.00), respectively. The nomogram based on the final fusion phase model was validated using calibration curve analysis and decision curve analysis, demonstrating good consistency and clinical utility. The nomogram-based risk classification system could correctly classify cases into three diverse risk groups: low-(ratio:3.6%; 0 160). Conclusions In our study, the risk assessment model makes it easy for physicians to assess the risk of grade ≥ 2 radiation pneumonitis at various phases in the radiotherapy process, and the risk classification system and nomogram identify the patient’s risk level after completion of radiation therapy.

PurposeOral mucositis is a common side effect of concurrent chemoradiotherapy (CCRT). This study aimed to determine whether cognitive behavioral therapy (CBT) could help prevent oral mucositis during chemoradiation therapy for locoregional advanced nasopharyngeal carcinoma (LA-NPC).Methods and materialsBetween July 15, 2020, and January 31, 2022, a randomized controlled phase II trial was conducted. Eligible patients (N=282, 18-70 years old) with pathologically diagnosed LA-NPC were randomly assigned to receive CBT or treatment as usual (TAU) during CCRT (computer-block randomization, 1:1). The primary endpoints were the incidence and latency of oral mucositis.ResultsThe incidence of oral mucositis was significantly lower in the CBT group (84.8%; 95% confidence interval [CI], 78.7%-90.9%) than in the TAU group (98.6%; 95% CI, 96.6%-100%; P

PurposeRadiotherapy is one of the most important treatments for high-grade glioma (HGG), but the best way to delineate the target areas for radiotherapy remains controversial, so our aim was to compare the dosimetric differences in radiation treatment plans generated based on the European Organization for Research and Treatment of Cancer (EORTC) and National Research Group (NRG) consensus to provide evidence for optimal target delineation for HGG.MethodsWe prospectively enrolled 13 patients with a confirmed HGG from our hospital and assessed dosimetric differences in radiotherapy treatment plans generated according to the EORTC and NRG-2019 guidelines. For each patient, two treatment plans were generated. Dosimetric parameters were compared by dose–volume histograms for each plan.ResultsThe median volume for planning target volume (PTV) of EORTC plans, PTV1 of NRG-2019 plans, and PTV2 of NRG-2019 plans were 336.6 cm3 (range, 161.1–511.5 cm3), 365.3 cm3 (range, 123.4–535.0 cm3), and 263.2 cm3 (range, 116.8–497.7 cm3), respectively. Both treatment plans were found to have similar efficiency and evaluated as acceptable for patient treatment. Both treatment plans showed well conformal index and homogeneity index and were not statistically significantly different (P = 0.397 and P = 0.427, respectively). There was no significant difference in the volume percent of brain irradiated to 30, 46, and 60 Gy according to different target delineations (P = 0.397, P = 0.590, and P = 0.739, respectively). These two plans also showed no significant differences in the doses to the brain stem, optic chiasm, left and right optic nerves, left and right lens, left and right eyes, pituitary, and left and right temporal lobes (P = 0.858, P = 0.858, P = 0.701 and P = 0.794, P = 0.701 and P = 0.427, P = 0.489 and P = 0.898, P = 0.626, and P = 0.942 and P = 0.161, respectively).ConclusionThe NRG-2019 project did not increase the dose of organs at risk (OARs) radiation. This is a significant finding that further lays the groundwork for the application of the NRG-2019 consensus in the treatment of patients with HGGs.Clinical trial registrationThe effect of radiotherapy target area and glial fibrillary acidic protein (GFAP) on the prognosis of high-grade glioma and its mechanism, number ChiCTR2100046667. Registered 26 May 2021.

Abstract Neuroinflammation occurs early in Alzheimer’s disease (AD). The initial stage of AD is related to glial dysfunction, which contributes to impairment of Aβ clearance and disruption of synaptic connection. CEBPβ, a member of the CCAAT-enhancer-binding protein (CEBP) family, modulates the expression of inflammation-associated genes, and its expression is elevated in brains undergoing degeneration and injured brains. However, the mechanism underlying CEBPβ-mediated chronic inflammation in AD is unclear. In this study, we observed that increases in the levels of nuclear CEBPβ facilitated the interaction of CEBPβ with the NFκB p65 subunit, increasing the transcription of proinflammatory cytokines in the APP/PS1 mouse brain. Oral administration of nanocarrier-packaged carnosic acid (CA) reduced the aberrant activation of microglia and astrocytes and diminished mature IL-1β, TNFα and IL-6 production in the APP/PS1 mouse brain. CA administration reduced β-amyloid (Aβ) deposition and ameliorated cognitive impairment in APP/PS1 mice. We observed that CA blocked the interaction of CEBPβ with NFκB p65, and chromatin immunoprecipitation revealed that CA reduced the transcription of the NFκB target genes TNFα and IL-6. We confirmed that CA alleviated inflammatory mediator-induced neuronal degeneration and reduced Aβ secretion by inhibiting the CEBPβ-NFκB signalling pathway in vitro. Sulfobutyl ether-beta-cyclodextrin (SBEβCD) was used as the encapsulation agent for the CA-loaded nanocarrier to overcome the poor water solubility and enhance the brain bioavailability of CA. The CA nanoparticles (NPs) had no obvious toxicity. We demonstrated a feasible SBEβCD-based nanodelivery system targeting the brain. Our data provide experimental evidence that CA-loaded NPs are potential therapeutic agents for AD treatment.

Abstract Ferroptosis is a newly discovered mode of cell death that involves disorders in iron metabolism and the accumulation of reactive oxygen species (ROS) in the plasma membrane. Preeclampsia (PE) is a gestational idiopathic disease that is characterized by hypertension and albuminuria, begins after 20 weeks of pregnancy. DJ-1 is a prerequisite for activating and stabilizing Nrf2 to allow translocation to the nucleus to carry out further functions. Detecting the expression levels of DJ-1, the Nrf2/GPX4 signaling pathway and ferroptosis markers in placental tissues of pregnant women with and without PE. Analyzing the effects of the ferroptosis inducer (RSL3) and the inhibitor (Fer-1) on the mortality rate of BeWo cells and DJ-1+/+, DJ-1−/− BeWo cells. Ferroptosis markers (MDA concentration and morphology of trophoblast cells) and DJ-1 and its downstream the Nrf2/GPX4 signaling pathway increased significantly in PE pathological state. The expression levels of DJ-1 protein in the control group and the PE group were positively correlated with the expression levels of Nrf2/GPX4 signaling pathway protein, and negatively correlated with the MDA concentration. BeWo cells were sensitive to the ferroptosis inducer (RSL3) and the inhibitor (Fer-1). The high expression levels of DJ-1 in BeWo cells can resist ferroptosis by regulating the Nrf2/GPX4 signaling pathway. Ferroptosis is involved in the pathogenesis of PE. DJ-1 can mediate the trophoblast cells ferroptosis and play a protective role in the pathogenesis of preeclampsia by regulating the Nrf2/GPX4 signaling pathway.

In the process of applying cold-stretching process to normal pressure vessel, the vessel will undergo two stages of elastic and plastic deformations. If the plastic deformation occurs, the minor change of deformation in the vessel is sensitive to the pressure. Therefore, the reasonable control of the deformation in the vessel is one of the key steps in the cold-stretching process. The resistance strain gauges（RSG） were pasted in the main parts of the vessel to determine the relationship between the elastic deformation of the corresponding position and the cold-stretching pressure applied gradually. In addition, the verification of the reliability of the finite element（FE） analysis was carried out based on strain measuring results. In the plastic deformation stage, the FE was used to analyze the overall deformation law of cylinder, head and around the nozzle of the vessel under the cold-stretching pressure, meanwhile the position where the maximum deformation occurred in each part of the vessel was obtained. The results show that the local maximum deformation of the vessel is 8.24%, which appears inside of the nozzle root, and meets the requirement of local maximum deformation of no more than 10% in the current standards.

Pearls, a well-known organic gemstone, are popular for their attractive lustre and rich colour. The pigmentation and colour of pearls have never been clearly explained. Understanding the pigments and colour origin of pearls can be a guide for artificial cultivation and rational conservation. In this study, Chinese freshwater cultured pearls were collected as research samples. The appearance and colour characteristics of pearls were characterised using D65 standard light source photography and UV–Vis spectroscopy, the molecular structure of the pigments in the pearls was characterised using Raman spectroscopy, and Density Functional Theory (DFT) calculations were used to reveal the characteristics of the pigments in the pearls in terms of molecular structure and electronic excitation. It was proposed that freshwater pearls are coloured with polyene pigments, with the chain length of the polyene determining the type of colour and the concentration of the polyene determining the colour intensity of the pearl. The HOMO–LUMO transition of conjugated polyenes is intrinsically responsible for the colour of pearls. Many colour-rich biominerals also have similar Raman spectral features to pearls, and this study has wider implications for understanding the nature of pigments and their colour origins.

Based on the excellent physical properties and flexible molecular modifiability, modified silicone resins have received favorable attention in the field of microelectronics, and recently a number of modified silicone resins have appeared while few breakthroughs have been made in low dielectric constant (low-k) materials field due to the limitations of structure or the curing process. In this work, functional silicone resin with different BCB contents was prepared with two monomers. The resins showed low dielectric constant (k = 2.77 at 10 MHz) and thermal stability (T5% = 495.0 °C) after curing. Significant performance changes were observed with the increase in BCB structural units, and the functional silicone obtained does not require melting and dissolution during processing because of good fluidity at room temperature. Moreover, the mechanical properties of silicone resins can be also controlled by adjusting the BCB content. The obtained silicone resins could be potentially used in the field of electronic packaging materials.

Conch pearl is a calcareous concretion produced by the Queen conch mollusk and is of extremely high economic value. Its attractive pink color has remained a mystery for hundreds of years. This difficulty limits the development of cultivation and preservation technology of conch pearl. Due to its super-high value, it is generally impossible to use destructive chemical analysis methods. Here, various nondestructive spectroscopic analysis methods and theoretical calculations were used to reveal the color origin of pink conch pearl. The experimental Raman and UV-Vis spectroscopies were used to characterize the color and pigments. We further discuss the pigments in conch pearl by comparing the Raman spectral characteristics and pigments of the red coral. Based on the characteristics of the experimental spectra, we speculate that the carotenoids color the conch pearl. The theoretical Raman and UV-Vis spectra of all-trans polyene and carotenoids were simulated using DFT calculations. According to the results, we proposed that the pigments in pink conch pearl are polyenes containing 11 shortened C–C bonds with multiplicities > 1.5, which may be demethylated carotenoids.

Objective To investigate the findings of MR imaging and their clinical value in diagnosis of left renal congestion in children with nutcracker syndrome (NCS). Methods All the 39 children (23 boys and 16 girls, mean age of 11±3 years) with NCS diagnosed at our hospital from Jun 2018 to Mar 2019 were enrolled in this study. Plain scanning sequence of T2WI was performed to measure the difference in signal intensity between the renal medulla and cortex (MC value) and calculate the absolute value of the difference between the MC values of both kidneys (BR value). Then, the children were divided into congestion group (n=25) and non-congestion group (n=14) according to whether a different renal signal existed between the 2 kidneys. The correlation of MRI findings and clinical biochemical data were analyzed with aid of statistics software SPSS 21.0. Results In the patients with congested left kidney, the medullary signals were reduced at T2WI, which rendered a distinct signal difference between the 2 kidneys. The patients from the congestion group had significantly higher BR value (P < 0.001) and obvious differences in MC value than those from the non-congestion group. There were no statistical differences in the incidence rates of hematuria (P=0.614), 24-hour urine protein quantification (P=0.429), and serum levels of urea nitrogen (P=0.420) and urinary creatinine (P=0.781) between the 2 groups. ROC curve analysis showed that when BR value >2.4, left renal congestion was valid, with higher diagnostic value (AUC=0.894), but 24-hour urine protein quantification (AUC=0.579) and serum levels of urea nitrogen (AUC=0.579) and urinary creatinine (AUC=0.527) had lower diagnostic values. Conclusion Inter-kidney MRI signal difference in children with NCS is a reliable sign to judge whether a congested left kidney exists; whereas clinical biochemical indices are not.

Polycarbosilanes have been considered as potential materials used in electronic packaging and circuit boards owing to their excellent low-dielectric performance. In this work, we prepared new hyperbranched carbosilane oligomers (HCBOs) which were functionalized by benzocyclobutene (BCB) groups. HCBOs can be thermally cured to produce transparent (HCBRs) with low dielectric constant and high thermostability.

With the continuous development of business intelligence technology, the application research of decision support systems (DSSs) is deepening. In China, the work in this area started relatively late, and there are few DSS research cases to assist in marketing decision-making. Currently, marketing decision support systems have shortcomings in data integration, historical data, query functions, and data analysis. This article analyzes the characteristics of marketing decision-making, discusses the application of data warehouse, OLAP, and data mining technology in marketing decision support systems, and designs a marketing decision support system based on data mining technology. The system uses a BP neural network to conduct data mining marketing forecasting. A three-layer network model for marketing prediction is established, with sales time, product price, and customer purchasing power as network inputs and output as the sales volume of a certain type of product in different locations. The test results show that the average absolute percentage error of this method is 15.13%, and the prediction accuracy is high. Research shows that with the continuous development of data mining technology, the system cannot only help users conduct scientific and reasonable marketing decision-making analyses, making the marketing decision-making process more scientific and reasonable, but also can bring new ideas to enterprise decision-makers, promoting the continuous improvement and progress of the system.

Abstract Deltacoronavirus is the last identified Coronaviridae subfamily genus. Differing from other coronavirus (CoV) genera, which mainly infect birds or mammals, deltacoronaviruses (δ‐CoVs) reportedly infect both animal types. Recent studies show that a novel δ‐CoV, porcine deltacoronavirus (PDCoV), can also infect calves and chickens with the potential to infect humans, raising the possibility of cross‐species transmission of δ‐CoVs. Here, we explored the deep phylogenetic history and cross‐species transmission of δ‐CoVs. Virus–host cophylogenetic analyses showed that δ‐CoVs have undergone frequent host switches in birds, and sparrows may serve as the unappreciated hubs for avian to mammal transmission. Our molecular clock analyses show that PDCoV possibly originated in Southeast Asia in the 1990s and that the PDCoV cluster shares a common ancestor with Sparrow‐CoV of around 1,810. Our findings contribute valuable insights into the diversification, evolution, and interspecies transmission of δ‐CoVs and the origin of PDCoV, providing a model for exploring the relationships of δ‐CoVs in birds and mammals.

BACKGROUND: Both defects in mismatch repair (dMMR) and high microsatellite instability (MSI-H) have been recognised as crucial biomarkers that guide treatment strategies and disease management in colorectal cancer (CRC). As MMR and MSI tests are being widely conducted, an increasing number of MSI-H tumours have been identified in CRCs with mismatch repair proficiency (pMMR). The objective of this study was to assess the clinical features of patients with pMMR/MSI-H CRC and elucidate the underlying molecular mechanism in these cases. METHODS: From January 2015 to December 2018, 1684 cases of pMMR and 401 dMMR CRCs were enrolled. Of those patients, 93 pMMR/MSI-H were identified. The clinical phenotypes and prognosis were analysed. Frozen and paraffin-embedded tissue were available in 35 patients with pMMR/MSI-H, for which comprehensive genomic and transcriptomic analyses were performed. FINDINGS: In comparison to pMMR/MSS CRCs, pMMR/MSI-H CRCs exhibited significantly less tumour progression and better long-term prognosis. The pMMR/MSI-H cohorts displayed a higher presence of CD8+ T cells and NK cells when compared to the pMMR/MSS group. Mutational signature analysis revealed that nearly all samples exhibited deficiencies in MMR genes, and we also identified deleterious mutations in MSH3-K383fs. INTERPRETATION: This study revealed pMMR/MSI-H CRC as a distinct subgroup within CRC, which manifests diverse clinicopathological features and long-term prognostic outcomes. Distinct features in the tumour immune-microenvironment were observed in pMMR/MSI-H CRCs. Pathogenic deleterious mutations in MSH3-K383fs were frequently detected, suggesting another potential biomarker for identifying MSI-H. FUNDING: This work was supported by the Science and Technology Commission of Shanghai Municipality (20DZ1100101).

Circular RNAs (circRNAs) have been found to be important mediators of many biological processes in the growth and metastasis of various cancers. However, the potential roles of most circRNAs in the progression of bladder cancer remain unclear. In this research, we investigate the role of circKIF4A (hsa_circ_0007255) in the development and progression of bladder cancer. Detected by qRT-PCR analysis, circKIF4A was significantly upregulated in bladder cancer tissues and cell lines. We conducted CCK-8, colony-formation, transwell and mouse xenograft assays to explore the function of circKIF4A in bladder cancer. Functionally, knockdown of circKIF4A inhibited the proliferation and colony-formation ability of bladder cancer cells. Migration and metastatic ability were dramatically decreased after transfection with small interfering RNA targeting circKIF4A in both in vitro and in vivo assays. Mechanically, luciferase reporter assays and RNA immunoprecipitation assays were carried out to elucidate the underlying molecular mechanism of circKIF4A. The results revealed that circKIF4A sponges miR-375/1231 to promote bladder cancer progression by upregulating NOTCH2. Generally, our research unveils the essential role of circKIF4A-miR-375/1231-NOTCH2 axis in bladder cancer progression possibly via the competing endogenous RNA mechanism.

One of the key features of acute myeloid leukemia (AML), a group of very aggressive myeloid malignancies, is their strikingly heterogenous outcomes. Accurate biomarkers are needed to improve prognostic assessment. Glutamate oxaloacetate transaminase 1 (GOT1) is essential for cell proliferation and apoptosis by regulating cell's metabolic dependency on glucose. It is unclear whether the expression level of GOT1 has clinical implications in AML. Therefore, we analyzed the data of 155 AML patients with GOT1 expression information from The Cancer Genome Atlas (TCGA) database. Among them, 84 patients were treated with chemotherapy alone, while 71 received allogeneic hematopoietic stem cell transplantation (allo-HSCT). In both treatment groups, high GOT1 expression was associated with shorter event-free survival (EFS) and overall survival (OS) (all P < 0.05). Multivariate analysis identified several independent risk factors for both EFS and OS in the chemotherapy-only group, including high GOT1 expression, age ≥60 years, white blood cell count ≥15 × 109/L, bone marrow blasts ≥70%, and DNMT3A, RUNX1 or TP53 mutations (all P < 0.05); but in the allo-HSCT group, the only independent risk factor for survival was high GOT1 expression (P < 0.05 for both EFS and OS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the genes related to GOT1 expression were mainly concentrated in “hematopoietic cell lineage” and “leukocyte transendothelial migration” signaling pathways. Collectively, GOT1 expression may be a useful prognostic indicator in AML, especially in patients who have undergone allo-HSCT.

Benzocyclobutene-modified silsesquioxane (BCB-POSS) and divinyl tetramethyl disiloxane-bisbenzocyclobutene (DVS-BCB) prepolymer were introduced into the containing benzocyclobutene (BCB) unit matrix resin P(4-MB-co-1-MP) polymerized from 1-methyl-1-(4-benzocyclobutenyl) silacyclobutane (4-MSCBBCB) and 1-methyl-1-phenylsilacyclobutane (1-MPSCB), respectively. The low dielectric constant (low-k) siloxane/carbosilane hybrid benzocyclobutene resin composites, P(4-MB-co-1-MP)/BCB-POSS and P(4-MB-co-1-MP)/DVS-BCB, were prepared. The curing processes of the composites were assessed via Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The effects on dielectric properties and heat resistance of those composites with different proportion of BCB-POSS and DVS-BCB were investigated using an impedance analyzer and thermogravimetric analyzer (TGA), respectively. The thermal curing of composites could be carried out by ring-opening polymerization (ROP) of the BCB four-member rings of BCB-POSS or DVS-BCB and those of P(4-MB-co-1-MP). With increasing the proportion of BCB-POSS to 30%, the 5% weight loss temperature (T5%) of P(4-MB-co-1-MP)/BCB-POSS composites was raised visibly, whereas the dielectric constant (k) was decreased owing to the introduction of nanopores into POSS. For P(4-MB-co-1-MP)/DVS-BCB composites, the T5% and k were slightly raised with increasing the proportion of DVS-BCB. The above results indicated that the BCB-POSS showed advantages over conventional fillers to simultaneously improve thermostability and decrease k.