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Abstract Background To evaluate the utility of glucose chemical exchange saturation transfer (glucoCEST) MRI with non-contrast injection in predicting the histological grade of rectal cancer. Methods This prospective analysis included 60 patients with preoperative rectal cancer who underwent pelvic glucoCEST, amide proton transfer-weighted imaging (APTWI), and diffusion-weighted imaging (DWI). In total, 21 low-grade and 39 high-grade cases were confirmed by postoperative pathology. The MTRasym (1.2 ppm), MTRasym (3.5 ppm), and apparent diffusion coefficient (ADC) values of lesions between the low-grade and high-grade groups were compared. The area under the receiver operating characteristic curve (AUC) was generated to evaluate the diagnostic performance of each technique. Logistic regression (LR) analysis was applied to determine independent predictors and for multi-parameter combined diagnosis. Results Elevated MTRasym (1.2 ppm), MTRasym (3.5 ppm) values and lower ADC values were observed in the high-grade group compared with low-grade cases (all p

Abstract Background Multiple models intravoxel incoherent motion (IVIM) based 18F-fluorodeoxyglucose positron emission tomography-magnetic resonance(18F-FDG PET/MR) could reflect the microscopic information of the tumor from multiple perspectives. However, its value in the prognostic assessment of non-small cell lung cancer (NSCLC) still needs to be further explored. Objective To compare the value of 18F-FDG PET/MR metabolic parameters and diffusion parameters in the prognostic assessment of patients with NSCLC. Meterial and methods Chest PET and IVIM scans were performed on 61 NSCLC patients using PET/MR. The maximum standard uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), diffusion coefficient (D), perfusion fraction (f), pseudo diffusion coefficient (D*) and apparent diffusion coefficient (ADC) were calculated. The impact of SUVmax, MTV, TLG, D, f, D*and ADC on survival was measured in terms of the hazard ratio (HR) effect size. Overall survival time (OS) and progression-free survival time (PFS) were evaluated with the Kaplan–Meier and Cox proportional hazard models. Log-rank test was used to analyze the differences in parameters between groups. Results 61 NSCLC patients had an overall median OS of 18 months (14.75, 22.85) and a median PFS of 17 months (12.00, 21.75). Univariate analysis showed that pathological subtype, TNM stage, surgery, SUVmax, MTV, TLG, D, D* and ADC were both influential factors for OS and PFS in NSCLC patients. Multifactorial analysis showed that MTV, D* and ADC were independent predicting factors for OS and PFS in NSCLC patients. Conclusion MTV, D* and ADC are independent predicting factors affecting OS and PFS in NSCLC patients. 18F-FDG PET/MR-derived metabolic parameters and diffusion parameters have clinical value for prognostic assessment of NSCLC patients.

Abstract Background Clinical trials have shown that immunotherapy based on Vγ9Vδ2 T cells (Vδ2 T cells) is safe and well-tolerated for various cancers including cervical cancer (CC), but its overall treatment efficacy remains limited. Therefore, exploring the mechanisms underlying the suboptimal efficacy of Vδ2 T cell-based cancer immunotherapy is crucial for enabling its successful clinical translation. Methods Tumor samples from CC patients and CC cell line-derived xenograft (CDX) mice were analyzed using flow cytometry to examine the exhausted phenotype of tumor-infiltrating Vδ2 T cells. The interrelationship between BTN3A1 expression and Vδ2 T cells in CC, along with their correlation with patient prognosis, was analyzed using data from The Cancer Genome Atlas (TCGA) database. CC cell lines with BTN3A1 knockout (KO) and overexpression (OE) were constructed through lentivirus transduction, which were then co-cultured with expanded Vδ2 T cells, followed by detecting the function of Vδ2 T cells using flow cytometry. The pathways and transcription factors (TFs) related to BTN3A1-induced Vδ2 T cells exhaustion and the factors affecting BTN3A1 expression were identified by RNA-seq analysis, which was confirmed by flow cytometry, Western Blot, and gene manipulation. Results Tumor-infiltrating Vδ2 T cells exhibited an exhausted phenotype in both CC patients and CDX mice. BTN3A1 expressed in CC is highly enhancing exhaustion markers, while reducing the secretion of effector molecules in Vδ2 T cells. Blocking TCR or knocking down nuclear receptor subfamily 4 group A (NR4A) 2/3 can reverse BTN3A1-induced exhaustion in Vδ2 T cells. On the other hand, IFN-γ secreted by Vδ2 T cells promoted the expression of BTN3A1 and PD-L1. Conclusions Through binding γδ TCRs, BTN3A1 expressed on tumor cells, which is induced by IFN-γ, can promote Vδ2 T cells to upregulate the expression of TFs NR4A2/3, thereby affecting their activation and expression of exhaustion-related molecules in the tumor microenvironment (TME). Therefore, targeting BTN3A1 might overcome the immunosuppressive effect of the TME on Vδ2 T cells in CC.

OBJECTIVES: Fewer women have aortic dissection (AD) than men. This study was aimed to explore the clinical characteristics of AD in Chinese women. MATERIALS AND METHODS: Clinical manifestations, treatment methods, and prognosis of AD patients treated in the First Hospital of China Medical University from January 2010 to December 2019 were retrospectively analyzed. RESULTS: A total of 931 patients (240 female patients) were included in the study. The mean age was 53.48 ± 12.66 years. There was a smaller body mass index in female patients compared with male patients (25.23 ± 3.79 vs. 26.32 ± 4.04, P < 0.001). The percentages of women who reported regular cigarette and alcohol consumption were lower than those of men (8.7% vs. 36.3% and 7.2% vs. 22.1%, respectively, P < 0.001 for both). In terms of computed tomography (CT) imaging, the proportion of women with Type III arches was lower (11.3% vs. 26.0%, P < 0.001). The degree of AD tear in female patients was more limited than that in male patients. about 24.6% of female patients had AD in the superior arch branch, whereas 48.9% of male patients had AD in the iliac artery. Descending aortic branch involvement was less common in female patients (60.4% vs. 40.3%, P < 0.001), whereas AD occurred more frequently in the coeliac trunk in male patients (28.1% vs. 20.0%, P = 0.014). The level of false lumen thrombosis was higher in female patients compared with male patients at all levels of the aorta (P < 0.001). In-hospital mortality was significantly higher in female patients with Type A AD than that in male patients (11.2% vs. 4.0%, P = 0.014), whereas stroke and myocardial ischemia were more common in female patients (8.8% vs. 4.6%, P = 0.018; 13.8% vs. 8.5%, P = 0.02). The all-cause and aorto-related mortality was lower in female patients (9.8% vs. 13.7%, P = 0.195; 5.8% vs. 11.4%, P = 0.034). However, there was no significant difference in the long-term survival rates between male and female patients (P = 0.762). Cox regression analysis showed that hypertension, smoking, alcohol consumption, advanced age, and degree of AD tear were the risk factors affecting the long-term survival rate, whereas the false lumen thrombosis was the protective factor. CONCLUSION: Female patients had more stable clinical manifestations and slighter imaging changes in contrast-enhanced CT. Gender only had a certain impact on perioperative mortality but had no impact on long-term survival. These important clinical features and prognoses should be considered to improve clinical outcomes in female patients.

Abstract The treatment, disposal, and resource utilization of waste mud are challenges for engineering construction. This study investigates the road performance of waste mud–solidified soil and explains how solidifying materials influence the strength and deformation characteristics of waste mud. Unconfined compressive strength tests, consolidated undrained triaxial shear tests, resonant column tests, and consolidation compression tests were conducted to evaluate the solidification effect. The test results show that with an increase in cement content from 5 to 9%, the unconfined compressive strength of the waste mud–solidified soil increased by over 100%, the curing time was extended from 3 to 28 days, and the unconfined compressive strength increased by approximately 70%. However, an increase in initial water content from 40 to 60% reduced the unconfined compressive strength by 50%. With the increase of cement content from 5 to 9%, the cohesion and friction angles increased by approximately 78% and 24%, respectively. The initial shear modulus under dynamic shear increased by approximately 38% and the shear strain corresponding to a damping ratio decay to 70% of the initial shear modulus decreased by nearly 11%. The compression coefficient decreased by approximately 55%. Scanning electron microscopy and X-ray diffraction tests showed that a higher cement content led to the formation of more hydration reaction products, especially an increase in the content of AlPO4, which can effectively fill the pores between soil particles, enhance the bonding between soil particles, and form a skeleton with soil particles to improve compactness. Consequently, the strength of the waste mud–solidified soil increased significantly while its compressibility decreased. This study can provide data support for dynamic characteristics of waste mud solidified soil subgrade.

Abstract Purpose 123I-Ioflupane SPECT is an effective tool for the diagnosis and progression assessment of Parkinson’s disease (PD). Radiomics and deep learning (DL) can be used to track and analyze the underlying image texture and features to predict the Hoehn-Yahr stages (HYS) of PD. In this study, we aim to predict HYS at year 0 and year 4 after the first diagnosis with combined imaging, radiomics and DL-based features using 123I-Ioflupane SPECT images at year 0. Methods In this study, 161 subjects from the Parkinson’s Progressive Marker Initiative database underwent baseline 3T MRI and 123I-Ioflupane SPECT, with HYS assessment at years 0 and 4 after first diagnosis. Conventional imaging features (IF) and radiomic features (RaF) for striatum uptakes were extracted from SPECT images using MRI- and SPECT-based (SPECT-V and SPECT-T) segmentations respectively. A 2D DenseNet was used to predict HYS of PD, and simultaneously generate deep features (DF). The random forest algorithm was applied to develop models based on DF, RaF, IF and combined features to predict HYS (stage 0, 1 and 2) at year 0 and (stage 0, 1 and ≥ 2) at year 4, respectively. Model predictive accuracy and receiver operating characteristic (ROC) analysis were assessed for various prediction models. Results For the diagnostic accuracy at year 0, DL (0.696) outperformed most models, except DF + IF in SPECT-V (0.704), significantly superior based on paired t-test. For year 4, accuracy of DF + RaF model in MRI-based method is the highest (0.835), significantly better than DF + IF, IF + RaF, RaF and IF models. And DL (0.820) surpassed models in both SPECT-based methods. The area under the ROC curve (AUC) highlighted DF + RaF model (0.854) in MRI-based method at year 0 and DF + RaF model (0.869) in SPECT-T method at year 4, outperforming DL models, respectively. And then, there was no significant differences between SPECT-based and MRI-based segmentation methods except for the imaging feature models. Conclusion The combination of radiomic and deep features enhances the prediction accuracy of PD HYS compared to only radiomics or DL. This suggests the potential for further advancements in predictive model performance for PD HYS at year 0 and year 4 after first diagnosis using 123I-Ioflupane SPECT images at year 0, thereby facilitating early diagnosis and treatment for PD patients. No significant difference was observed in radiomics results obtained between MRI- and SPECT-based striatum segmentations for radiomic and deep features.

Abstract The aim of the current study was to investigate the effects of ingesting different dosages of caffeine (CAF) prior to plyometric jump training (PJT) on sport-related performance and physiological parameters in male basketball players. Twenty-four young athletes were randomly divided into 3 groups and performed 6 weeks of PJT while consuming 3 mg·kg–1 of body mass caffeine (CAF3, n = 8), 6 mg·kg–1 body mass caffeine (CAF6, n = 8) or placebo (PL; n = 8) one hour prior to each training session. Before and after the 6-week PJT, the players were evaluated for field-based basketball-specific performance measures (vertical jump, 20-m sprint, Illinois change of direction speed [CODS], and maximal strength) and lab-based physiological (aerobic capacity and anaerobic power) parameters. CAF3, CAF6, and PL groups demonstrated significant improvements in vertical jump (ES = 1.07, 1.45, and 1.1, respectively), 20-m sprint (ES = – 0.50, – 0.61, and – 0.36), change of direction performance (ES = – 1.22, – 1.26, and – 1.09), maximal strength (ES = 1.68, 2.29, and 1.17), maximum oxygen uptake (V̇O2max) (ES = 1.09, 1.59, and 0.92), and peak (ES = 1.82, 1.85, and 0.82) and average power output (ES = 1.39, 1.32, and 1.07) after 6 weeks of training. Comparative analysis of individual adaptive responses to training indicated that the CAF6 led to insignificantly greater effects in vertical jump (ES = 1.45), maximal strength (ES = 2.29), and V̇O2max (ES = 1.59) with lower residuals in individual changes and lower coefficient of variations (CV) in mean group changes. Regarding sprint and CODS performance, both experimental groups indicated similar changes, residuals in individual changes, and CVs in mean group changes. Overall, consuming 6 mg·kg–1 body mass caffeine induces superior adaptations in aerobic fitness, anaerobic power, and sport-specific performance measures, with lower inter-individual variability in the adaptations and more homogenized changes over the training period.

Abstract Piezoceramic membranes have emerged as a prominent solution for membrane fouling control. However, the prevalent use of toxic lead and limitations of vibration-based anti-fouling mechanism impede their wider adoption in water treatment. This study introduces a Mn/BaTiO3 piezoceramic membrane, demonstrating a promising in-situ anti-fouling efficacy and mechanism insights. When applied to an Alternating Current at a resonant frequency of 20 V, 265 kHz, the membrane achieves optimal vibration, effectively mitigating various foulants such as high-concentration oil (2500 ppm, including real industrial oil wastewater), bacteria and different charged inorganic colloidal particles, showing advantages over other reported piezoceramic membranes. Importantly, our findings suggest that the built-in ultrasonic vibration of piezoceramic membranes can generate reactive oxygen species. This offers profound insights into the distinct anti-fouling processes for organic and inorganic wastewater, supplementing and unifying the traditional singular vibrational anti-fouling mechanism of piezoceramic membranes, and potentially propelling the development of piezoelectric catalytic membranes.

ABSTRACT The widespread sulfonamide resistance genes sul1, sul2, and sul3 in food and gut bacteria have attracted considerable attention. In this study, we assessed the in vivo fitness of sul gene-dependent sulfonamide-resistant Escherichia coli, using a murine model. High fitness costs were incurred for sul1 and sul3 gene-dependent E. coli strains in vivo. A fitness advantage was found in three of the eight mice after intragastric administration of sul2 gene-dependent E. coli strains. We isolated three compensatory mutant strains (CMSs) independently from three mice that outcompeted the parent strain P2 in vivo. Whole-genome sequencing revealed seven identical single nucleotide polymorphism (SNP) mutations in the three CMSs compared with strain P2, an additional SNP mutation in strain S2-2, and two additional SNP mutations in strain S2-3. Furthermore, tandem mass tag-based quantitative proteomic analysis revealed abundant differentially expressed proteins (DEPs) in the CMSs compared with P2. Of these, seven key fitness-related DEPs distributed in two-component systems, galactose and tryptophan metabolism pathways, were verified using parallel reaction monitoring analysis. The DEPs in the CMSs influenced bacterial motility, environmental stress tolerance, colonization ability, carbohydrate utilization, cell morphology maintenance, and chemotaxis to restore fitness costs and adapt to the mammalian gut environment.IMPORTANCESulfonamides are traditional synthetic antimicrobial agents used in clinical and veterinary medical settings. Their long-term excessive overuse has resulted in widespread microbial resistance, limiting their application for medical interventions. Resistance to sulfonamides is primarily conferred by the alternative genes sul1, sul2, and sul3 encoding dihydropteroate synthase in bacteria. Studying the potential fitness cost of these sul genes is crucial for understanding the evolution and transmission of sulfonamide-resistant bacteria. In vitro studies have been conducted on the fitness cost of sul genes in bacteria. In this study, we provide critical insights into bacterial adaptation and transmission using an in vivo approach.

Abstract Objectives This study aimed to examine the impact of pertussis on the global, regional, and national levels between 1990 and 2019. Methods Data on pertussis on a global scale from 1990 to 2019 were collected from the 2019 Global Burden of Disease Study. We performed a secondary analysis to report the global epidemiology and disease burden of pertussis. Results During the period spanning from 1990 to 2019, pertussis exhibited a steady global decline in the age-standardized incidence rate (ASIR), age-standardized disability-adjusted life years rate (ASYR), and age-standardized death rate (ASDR). Nevertheless, upon delving into an in-depth analysis of various regions, it was apparent that ASIR in southern sub-Saharan Africa, ASYR and ASDR in high-income North America, and ASDR in Western Europe and Australasia, were witnessing an upward trajectory. Moreover, a negative correlation was observed between the Socio‑demographic Index (SDI) and burden inflicted by pertussis. Notably, the incidence of pertussis was comparatively lower in men than in women, with 0–4-year-olds emerging as the most profoundly affected demographic. Conclusion The global pertussis burden decreased from 1990 to 2019. However, certain regions and countries faced an increasing disease burden. Therefore, urgent measures are required to alleviate the pertussis burden in these areas.

Abstract Background Treating the coronal dens invaginatus (CDI) with pulp infection commonly involves the removal of invagination, which increases the risk of perforation and fracture, and compromises the tooth structure. Minimally invasive endodontic management of CDI is highly recommended. This report describes two cases of type II CDI with the application of personalized templates. Case presentation Two cases of type II CDI, affecting the main root canal in a maxillary canine and a lateral incisor, were diagnosed. A guided endodontics (GE) approach was applied. Cone-beam computed tomography and intraoral scans were imported and aligned in a virtual planning software to design debridement routes and templates. The MICRO principle (which involves the aspects of Mechanical (M) debridement, Irrigation (I), Access cavities (C), Rectilinear routes (R), and Obstruction (O)) was proposed for designing optimal debridement routes for future applications. The templates were innovatively personalized and designed to preserve the tooth structure maximally while effectively debriding the root canal. Root canal treatment with supplementary disinfection was then performed. The follow-up of the two patients revealed favorable clinical and radiographic outcomes. Conclusions The GE approach could be a feasible method for preserving healthy dental structure while effectively debriding the root canal, thereby achieving successful and minimally invasive endodontic treatment for CDI.

Abstract Background The primary treatment for patients with myocardial infarction (MI) is percutaneous coronary intervention (PCI). Despite this, the incidence of major adverse cardiovascular events (MACEs) remains a significant concern. Our study seeks to optimize PCI predictive modeling by employing an ensemble learning approach to identify the most effective combination of predictive variables. Methods and results We conducted a retrospective, non-interventional analysis of MI patient data from 2018 to 2021, focusing on those who underwent PCI. Our principal metric was the occurrence of 1-year postoperative MACEs. Variable selection was performed using lasso regression, and predictive models were developed using the Super Learner (SL) algorithm. Model performance was appraised by the area under the receiver operating characteristic curve (AUC) and the average precision (AP) score. Our cohort included 3,880 PCI patients, with 475 (12.2%) experiencing MACEs within one year. The SL model exhibited superior discriminative performance, achieving a validated AUC of 0.982 and an AP of 0.971, which markedly surpassed the traditional logistic regression models (AUC: 0.826, AP: 0.626) in the test cohort. Thirteen variables were significantly associated with the occurrence of 1-year MACEs. Conclusion Implementing the Super Learner algorithm has substantially enhanced the predictive accuracy for the risk of MACEs in MI patients. This advancement presents a promising tool for clinicians to craft individualized, data-driven interventions to better patient outcomes.

BackgroundTemporomandibular joint disorders (TMD) are highly prevalent among people. Numerous investigations have revealed the impact of gut microbiota in many diseases. However, the causal relationship between Temporomandibular joint disorders and gut microbiota remains unclear.MethodsGenome-Wide Association Studies (GWAS) refer to the identification of sequence variations, namely single nucleotide polymorphisms (SNPs), existing across the entire human genome. GWAS data were collected on gut microbiota and TMD. Then, instrumental variables were screened through F-values and removal of linkage disequilibrium. These SNPs underwent mendelian analysis using five mathematical models. Sensitivity analysis was conducted to further verify the stability of the results. Pathogenic factors of TMD mediate the causal relationship between gut microbiota and TMD were explored through a two-step Mendelian randomization analysis. Finally, reverse mendelian analysis was conducted to account for potential reverse effects.ResultsThe analysis of the data in this article suggests that some gut microbiota, including Coprobacter, Ruminococcus torques group, Catenibacterium, Lachnospiraceae, Turicibacter, Victivallis, MollicutesRF9, Methanobacteriales, Methanobacteriaceae, FamilyXI, Methanobacteria were identified as risk factors, while Peptococcaceae provides protection for TMD.ConclusionThe research reveals the relation of gut microbiota in TMD. These findings provide insights into the underlying mechanisms and suggest potential therapeutic strategy.

The battle against depression in the elderly is crucial due to its significant impact on their quality of life, physical and cognitive health, increased risk of social isolation and suicide, as well as the associated higher healthcare costs. This research investigates the effects of traditional and augmented reality Tai Chi, using the virtual environment “Managed Tai Chi,” on depression in elderly individuals. The study involved 300 participants aged over 60 from the Beijing Medical Center, with an experimental period lasting six months and sessions held once a week. The Geriatric Depression Scale (GDS) was utilized as a diagnostic tool at the pre-test and post-test stages. The findings revealed that the VR group exhibited a more substantial reduction in depression compared to the traditional and control groups (p ≤ 0.05), indicating the enhanced efficacy of Tai Chi with VR augmentation in treating depression in the elderly.

Soft adhesive systems (SASs), which consist of a soft adhesive layer and/or soft adherends, have been extensively applied in advanced fields such as biomedicine, flexible electronics, and soft robotics. Understanding the fatigue failure of SASs is crucial for ensuring their structural safety and functional stability, as they are often subjected to fatigue loading. This paper systematically reviews the fatigue failure of SASs, aiming to provide a comprehensive understanding and contribute to the study of fatigue failure mechanisms and lifetime prediction of SASs. The review starts by introducing classical research methods for fatigue failure of adhesive systems, with a focus on total fatigue lifetime and fatigue crack growth (FCG). After summarizing the complexity of fatigue failure in SASs, it provides an overview of fatigue research for the three types of SASs: “soft interface”, “soft adherend”, and “soft-soft” adhesive systems. Then, the relations between the fatigue failure and energy dissipation of various SASs are specifically discussed noting that significant energy dissipation accompanying the cyclic deformation of SASs during fatigue loading can substantially affect the final fatigue failure of SASs. Finally, the current unresolved issues and challenges in this field are presented.

ABSTRACT The gastric microbial community plays a fundamental role in gastric cancer (GC), and the two main anatomical subtypes of GC, non-cardia and cardia GC, are associated with different risk factors (Helicobacter pylori for non-cardia GC). To decipher the different microbial spatial communities of GC, we performed a multicenter retrospective analysis to characterize the gastric microbiota in 223 GC patients, including H. pylori-positive or -negative patients, with tumors and paired adjacent normal tissues, using third-generation sequencing. In the independent validation cohort, both dental plaque and GC tumoral tissue samples were collected and sequenced. The prevalence of H. pylori and oral-associated bacteria was verified using fluorescence in situ hybridization (FISH) assays in GC tumoral tissues and matched nontumoral tissues. We found that the vertical distribution of the gastric microbiota, at the upper, middle, and lower third sites of GC, was likely an important factor causing microbial diversity in GC tumor tissues. The oral-associated microbiota cluster, which included Veillonella parvula, Streptococcus oralis, and Prevotella intermedia, was more abundant in the upper third of the GC. However, H. pylori was more abundant in the lower third of the GC and exhibited a significantly high degree of microbial correlation. The oral-associated microbiota module was co-exclusive with H. pylori in the lower third site of the GC tumoral tissue. Importantly, H. pylori-negative GC patients with oral-associated gastric microbiota showed worse overall survival, while the increase in microbial abundance in H. pylori-positive GC patients showed no difference in overall survival. The prevalence of V. parvula in both the dental plaque and GC tissue samples was concordant in the independent validation phase. We showed that the oral-associated species V. parvula and S. oralis were correlated with overall survival. Our study highlights the roles of the oral-associated microbiota in the upper third of the GC. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for H. pylori-negative GCs.IMPORTANCEOur study highlights the roles of the oral-associated microbiota in the upper third of gastric cancer (GC).We showed that the oral-associated species Veillonella parvula and Streptococcus oralis were correlated with overall survival. In addition, oral-associated species may serve as noninvasive screening tools for the management of GC and an independent prognostic factor for Helicobacter pylori-negative GCs.

Breast cancer (BRCA) is one of the most common malignant tumors affecting women worldwide. DNA methylation modifications can influence oncogenic pathways and provide potential diagnostic and therapeutic targets for precision oncology. In this study, we used non-parametric permutation tests to identify differentially methylated positions (DMPs) between paired tumor and normal BRCA tissue samples from the Cancer Genome Atlas (TCGA) database. Then, we applied non-negative matrix factorization (NMF) to the DMPs to derive eight distinct DNA methylation signatures. Among them, signatures Hyper-S3 and Hypo-S4 signatures were associated with later tumor stages, while Hyper-S1 and Hypo-S3 exhibited higher methylation levels in earlier stages. Signature Hyper-S3 displayed an effect on overall survival. We further validated the four stage-associated signatures using an independent BRCA DNA methylation dataset from peripheral blood samples. Results demonstrated that 24 commonly hypomethylated sites in Hypo-S4 showed lower methylation in BRCA patients compared to healthy individuals, suggesting its potential as an early diagnostic biomarker. Furthermore, we found that methylation of 23 probes from four stage-related signatures exhibited predictive power for immune therapy response. Notably, methylation levels of all three probes from the Hypo-S4 and activity of the Hypo-S4 demonstrated highly positive relevance to PD-L1 gene expression, implying their significant predictive values for immunotherapy outcomes. GO and KEGG pathway enrichment analysis revealed that genes with these 23 immunotherapy-related methylation probes are mainly involved in glycan degradation or protein deglycosylation. These methylation signatures and probes may serve as novel epigenetic biomarkers for predicting tumor immunotherapy response. Our findings provide new insights into precision oncology approaches for BRCA.

Ischemic stroke (IS), primarily caused by cerebrovascular obstruction, results in severe neurological deficits and has emerged as a leading cause of death and disability worldwide. Recently, there has been increasing exploration of the neuroprotective properties of the inert gas argon. Argon has exhibited impressive neuroprotection in many in vivo and ex vivo experiments without signs of adverse effects, coupled with the advantages of being inexpensive and easily available. However, the efficient administration strategy and underlying mechanisms of neuroprotection by argon in IS are still unclear. This review summarizes current research on the neuroprotective effects of argon in IS with the goal to provide effective guidance for argon application and to elucidate the potential mechanisms of argon neuroprotection. Early and appropriate argon administration at as high a concentration as possible offers favorable neuroprotection in IS. Argon inhalation has been shown to provide some long-term protection benefits. Argon provides the anti-oxidative stress, anti-inflammatory and anti-apoptotic cytoprotective effects mainly around Toll-like receptor 2/4 (TLR2/4), mediated by extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor kappa-B (NF-ĸB) and B-cell leukemia/lymphoma 2 (Bcl-2). Therefore, argon holds significant promise as a novel clinical neuroprotective gas agent for ischemic stroke after further researches to identify the optimal application strategy and elucidate the underlying mechanism.

Highlights This review introduces the potential of 2D electronics for post-Moore era and discusses their current progress in digital circuits, analog circuits, heterogeneous integration, sensing circuits, artificial intelligence chips, and quantum chips in sequence. A comprehensive analysis of the current trends and challenges encountered in the development of 2D materials is summarized. An in-depth roadmap outlining the future development of 2D electronics is presented, and the most accessible and promising avenues for 2D electronics are suggested.

Time series data of industrial chemical process are typically collected in two ways: distributed control system (DCS) and laboratory test. With the popularity of DCS, a large amount of industrial chemical process monitoring data can be collected (label-sufficient), which is commonly feature rich but information poor. Due to the variant design of the processes, some target features are still monitored through laboratory tests. Data collected in this way cannot support the training of deep learning models as a result of low monitoring frequency and the lack of historical data (label-insufficient). In this study, a reinforcement aided latent temporal feature transfer learning (RALTFTL) method is proposed. It predicts a label-insufficient feature in target domain by learning knowledge from a similar label-sufficient feature in source domain. A transfer learning framework characterized by using latent temporal feature is constructed. Autoencoder is conducted to construct the latent spaces and unify the number of latent features. Reinforcement learning approach is introduced to the framework for feature selection. By taking monitoring features as candidates and taking the improvement of accuracy as reward, it explores a subset of monitoring features that maximizes the accuracy of the prediction model in the target domain. A gas emission (NOx concentration) prediction task is taken as experiment using the practical data from two industrial chemical devices. The performance of RALTFTL is assessed, and the effectiveness of introduced approaches and mechanisms is verified.

The cytochrome P450 enzyme is one of the largest protein families identified in cuticle biosynthesis, plant growth, development, and stress response. In the present study, 28 members of the MdCYP86A family were identified in apple (Malus × domestica Borkh.). Chromosomal localization analysis found that 28 genes were distributed on 13 chromosomes in apple. Phylogenetic and conserved motifs analysis showed that MdCYP86As in apple is evolutionarily most closely related to Arabidopsis thaliana. Each gene contains a cytochrome P450 domain, suggesting that MdCYP86As are highly conserved during the evolution of the species. Cis-acting element analysis of the promoter identified various elements associated with stress response. MdCYP86A21 was cloned in the apple genome to investigate the function of MdCYP86A family genes. MdCYP86A21 responded to abiotic stress, including PEG, NaCl, and ABA. The tissue-specific expression patterns revealed that the highest expression tissue was in flower by real-time quantitative reverse transcription (RT-qPCR). Subcellular localization showed that MdCYP86A21 was localized in the endoplasmic reticulum. Further, the function of MdCYP86A21 to enhance the resistance to PEG and NaCl stress in apple calli was verified. These results contribute to further study on the function of MdCYP86As and provide a molecular basis for the study of apple stress tolerance.

Abstract In this paper, we consider the Cauchy problem of a compressible Navier–Stokes system of Eills-type non-Newtonian fluids. We investigate the time decay properties of classical solutions for the compressible non-Newtonian fluid equations. More specifically, we construct a new linearized system in terms of a combination of the solutions, and then we investigate the long-time behavior of the Cauchy problem for the three-dimensional isentropic compressible Eills-type non-Newtonian fluids with an initial perturbation.

SnBi based solders have attracted widespread attention due to their promising applications in heterogeneous integration and three-dimensional microelectronic packaging. However, the low melting point of SnBi based solder means their high homologous temperature during service, leading to fast coarsening of the microstructure, which can significantly impair the reliability of electron devices. It has been found that Bi grains in SnBi based solder interconnects grow significantly and exhibit a preferred orientation under thermal loading conditions, but the mechanisms underneath the preferential growth of Bi grains is yet to be understood. In this work, a phase field model incorporating the thermal stress effect is developed and employed to investigate the dynamic evolution of the microstructure of SnBi solder under thermal aging, and to capture the morphology changes of the grains with different orientations. It is demonstrated that Bi grains with c-axis parallel to the z-axis preferentially exist in eutectic SnBi solder under thermal aging, and Bi grains with a large angle between the c-axis and the z-axis are swallowed by the preferred grains. Moreover, there is a competitive evolution between grains with different orientations in the polycrystalline eutectic SnBi solder, due to the minimization of system elastic strain energy. Further mechanism analysis elucidates that the Bi grain orientation preference in SnBi solders is caused by the dependence of their Young’s modulus and coefficient of thermal expansion on the grain orientation, the favored grains possess a lower strain energy compared to other grains.

Conventional oxidation processes for alkyl aromatics to ketones employ oxidants that tend to generate harmful byproducts and cause severe equipment corrosion, ultimately creating critical environmental problems. Thus, in this study, a practical, efficient, and green method was developed for the synthesis of aromatic ketones by applying a bis(2-butoxyethyl) ether/O2 system under external catalyst-, additive-, and base-free conditions. This O2-mediated oxidation system can tolerate various functional groups and is suitable for large-scale synthesis. Diverse target ketones were prepared under clean conditions in moderate-to-high yields. The late-stage functionalization of drug derivatives with the corresponding ketones and one-pot sequential chemical conversions to ketone downstream products further broaden the application prospects of this approach.

Abstract Rainbands are essential to tropical cyclones (TCs), significantly affecting TC structure and intensity change. High‐resolution synthetic aperture radar (SAR) imagery can capture the footprints of rainbands caused by rain‐induced sea surface roughness modification. Using 464 SAR TC images, we investigated the rainband‐occurrence probability of TCs under different hemispheres, local times (LTs), intensities, and ocean basins. Results show that the rainband‐occurrence probability is highest in the downshear‐left quadrant for Northern Hemisphere TCs (downshear‐right quadrant for Southern Hemisphere TCs). For Northern Hemisphere TCs, the rainband‐occurrence probability is overall higher in the early morning (LT), and the peak region of rainband‐occurrence probability appears farther from the TC center in the evening (LT). Compared with weak TCs, the rainband‐occurrence probability becomes higher for strong TCs in the Northern Hemisphere. Furthermore, TCs have a higher rainband‐occurrence probability in the Northwest Pacific than in the North Atlantic and Northeast Pacific.

Abstract Drought has a paramount impact on global agriculture and food security. However, the study on future cropland areas that can incur drought is inadequate. This paper uses input parameters from 7 CMIP6 models for 7 future scenarios (SSP1‐1.9, SSP1‐2.6, SSP4‐3.4, SSP2‐4.5, SSP4‐6.0, SSP3‐7.0, and SSP5‐8.5) to measure South Asian cropland exposure to drought and its underlying factors. Some defined epochs such as 2021–2040 (near‐term), 2041–2060 (mid‐term), 2081–2100 (long‐term), and 1995–2014 (reference period) are designed to explore diverse outlooks of the change. The Standardized Precipitation Evapotranspiration Index and the Run theory methods are applied to detect drought. Results indicate an intensified cropland (under SSP4‐3.4, SSP3‐7.0, and SSP5‐8.5) in the Indo‐Gangetic Plain region of South Asia, where mostly the variation occurs among scenarios and periods. Notably, the future cropland exposed to drought will increase in the 2021–2040, and 2041–2060 periods, but it intends to decline during the 2081–2100. Relatively, the exposed cropland will upturn highest by 49.2% (SSP3‐7.0) in the mid‐term period and decrease by −8.2% (SSP5‐8.5) in the end future. Spatially, distributed cropland in the central, south‐west, and portion of the northeast of South Asia are subjective to be exposed largely, but it can drop greatly across the eastern part by the end future. Importantly, the climate change effect plays a grounding role in future exposure change over the region during the near to mid‐term periods, while the cropland change effect is predominant in the long‐term perspectives. However, these findings signify the urgency of policymaking focusing on drought mitigation to ensure food security.

For a directed graph D, it's deemed rainbow connected if each arc is assigned a different color, so that all paths from the vertex u to the vertex v are rainbow connected. Rainbow connection number refers to how many colors are needed in D to achieve rainbow connectivity. Among ordered vertex pair (u,v) with arc coloring, if both arcs and internal vertices exhibit unique colors, it is referred to as a total colored graph. As the total rainbow connection number indicates, the smallest number of colors are required to total-color D. This paper focuses on investigating the rainbow connection number of the biorientation of a connected graph, as well as the total rainbow connection number.

Lilium brownii F. E. Brown ex Miellez var. viridulum Baker (Longya lily) is a variety of Lilium brownii F.E. Br. ex Miellez. We used HS-SPME and GC-MS to screened the tissues of L. brownii roots, stems, bulbs, and leaves and obtained 2,4-DTBP as an autotoxic substance for subsequent analysis. 2,4-DTBP was highly autotoxic in some treatment groups. Based on changes in physiological indicators, we carried out transcriptomic analysis to investigate the mechanisms of autotoxicity of substances on L. brownii and obtained 188,505 Unigenes. GO and KEGG enrichment analyses showed that L. brownii responded differently to different concentrations and treatment times of 2,4-DTBP. We observed significant changes in genes associated with ROS, phytohormones, and MAPK signaling cascades. 2,4-DTBP affects chloroplasts, the integrity of the respiratory electron transport chain, and ribosomes, causing L. brownii autotoxicity. Our findings provide a practical genomic resource for future research on L. brownii autotoxicity and evidence for the mechanism of action of autotoxic substances.

Due to the harsh marine environment of chloride ion invasion and corrosion, the issues of long-term chloride transport and durability life evaluation for marine infrastructures constructed/maintained by recycled aggregate concrete (RAC) after enhancement remain poorly understood. For our studies, an accelerated carbonation modification method for recycled coarse aggregate (RCA) was adopted to prepare carbonated recycled coarse aggregate (CRCA) samples, and the macroproperties, i.e., apparent density and water absorption, of CRCA were enhanced by approximately 1.40-3.97% and 16.3-21.8%, respectively, compared with those of RCA. An in-door experiment for chloride transport into concrete specimens subjected to a simulated marine environment of alternating drying-wetting cycles was conducted. The chloride profiles and transport characteristics of carbonated recycled coarse aggregate concrete (CRCAC), recycled coarse aggregate concrete (RCAC), and natural coarse aggregate concrete (NCAC) were analysed and compared. The results indicated that the chloride penetration depths and concentrations of CRCAC were approximately 52.6-96.2% of those of RCAC, which highlighted the better chloride resistance of CRCAC. A chloride transport model for marine concrete structures with various coarse aggregate types in a corrosive marine environment was established. Taking a certain harbour wharf as an example, the durability life of this case considering the application of the CRCAC was evaluated based on the chloride transport model, and the durability life of the CRCAC structure was improved by approximately 28.10% compared with that of the RCAC. The CRCAC developed in this paper has improved mechanical performance and durability than those of RCAC, and it has the potential to replace the NCAC and further support the construction and maintenance of marine infrastructures.

The tooth profiles at different positions of the non-circular gear pitch curve have the characteristics of equal modulus but unequal curvature radius and polar diameter. The distribution characteristics of the envelope curve of each tooth profile formed during the hobbing process are different, which lead to the unequal envelope error of the tooth profile at different positions. Taking the basic linkage model of hobbing as the motion constraint, the geometric simulation scheme of the tooth profile generated by the intermittent cutting of the hob is constructed, and the correlation characteristics between the envelope distribution and the curvature radius of the pitch curve and the polar diameter are analyzed. The concept of equivalent hobs is introduced, the relationship model between envelope error and equivalent gear tooth number and equivalent hob groove number is built, and the calculation and position distribution of the maximum envelope error of different tooth profiles are analyzed. A hobbing model to improve the envelope error is proposed. The model can realize the change of the equivalent hob groove number at different positions of the non-circular curve through the hob shifting method, thereby the maximum value and uneven distribution of the envelope error are improved. This study provides theoretical support for the analysis of the tooth profile envelope error of the non-circular gear hobbing, which can predict the envelope error and guide the formulation of a reasonable machining plan.

Objective: To develop a rapid, efficient and visual method for the detection of bacterial colistin resistance gene mcr-1, so as to provide the basis and convenience for the development of its detection at the grassroots level. Methods: Using recombinase polymerase amplification combined with a lateral flow dipstick (RPA-LFD) assay, supplemented by a hand-held colloidal gold reader. According to the conserved sequence of the mcr-1 gene, a pair of specific RPA primers were designed and synthesized. Through the optimization of the reaction conditions and system, as well as the specificity test, sensitivity test, simulated food sample test and actual sample test, the RPA-LFD assay for visual and quantitative detection of bacterial colistin resistance gene mcr-1 was successfully established. Results: When the primer concentration was 400 nmol/L and the primer ratio was 1:1, the optimal reaction conditions of this method are Mg2+ concentration 14.0 mmol/L, reaction temperature 37 ℃ and reaction time 20 min. The sensitivity was good, the standard curve equation was y=0.117x+0.051, the quantification limit was 101~108 copies/μL, and the detection limit was 101 copies/μL, which was an order of magnitude lower than the PCR method and the detection result of the simulated sample was consistent with the PCR method. Carrying status of colistin resistance gene mcr-1 in each 15 pork samples, chicken samples, pig farm environmental samples, broiler farm environmental samples, Escherichia coli isolates and Enterobacter campylobacter isolates were analyzed by the established RPA-LFD assay. The detection rate of positive samples by RPA-LFD assay was consistent with that of conventional PCR method, and a total of 9 mcr-1 gene positive samples were detected. RPA-LFD quantitative analysis showed that the concentration of mcr-1 gene in positive samples was between 4.5×102~8.6×104 copies/µL. Conclition: The RPA-LFD detection method of the bacterial colistin resistance gene mcr-1 established in this study had strong specificity, high sensitivity, and simple operation, and could be widely used in grassroots inspections.

Abstract Background A substantial risk of contracting Human immunodeficiency virus (HIV) exists among men who have sex with men (MSM), and HIV infection rates have been rising. This study aimed to analyze the factors influencing the Chinese MSM population’s intention to test for HIV. Methods Nonprobability sampling techniques were employed in June 2022 to recruit MSM in Chongqing and Sichuan, China. The data were analyzed using structural equation modeling (SEM), which is based on the knowledge-attitude-behavior (KAB) theory. Results Among 1687 participants, 964 (57.1%) of the MSM were willing to have an HIV test. The results of the structural equation modeling (SEM) showed that knowledge, attitude, and behavior all influenced the testing intention, with attitude having the greatest impact (total effect of 0.22). Conclusion HIV testing needs to be increased among MSM as they exhibit a moderate willingness to test. Improving education on HIV knowledge and risk behavior might enhance the willingness of MSM to test for HIV in China.

Abstract Background Recurrent or metastatic cervical cancer (r/m CC) often has poor prognosis owing to its limited treatment options. The development of novel therapeutic strategies has been hindered by the lack of preclinical models that accurately reflect the biological and genomic heterogeneity of cervical cancer (CC). Herein, we aimed to establish a large patient-derived xenograft (PDX) biobank for CC, evaluate the consistency of the biologic indicators between PDX and primary tumor tissues of patients, and explore its utility for assessing patient’s response to conventional and novel therapies. Methods Sixty-nine fresh CC tumor tissues were implanted directly into immunodeficient mice to establish PDX models. The concordance of the PDX models with their corresponding primary tumors (PTs) was compared based on the clinical pathological features, protein biomarker levels, and genomic features through hematoxylin & eosin staining, immunohistochemistry, and whole exome sequencing, respectively. Moreover, the clinical information of CC patients, RNA transcriptome and immune phenotyping of primary tumors were integrated to identify the potential parameters that could affect the success of xenograft engraftment. Subsequently, PDX model was evaluated for its capacity to mirror patient’s response to chemotherapy. Finally, PDX model and PDX-derived organoid (PDXO) were utilized to evaluate the therapeutic efficacy of neratinib and adoptive cell therapy (ACT) combination strategy for CC patients with human epidermal growth factor receptor 2 (HER2) mutation. Results We established a PDX biobank for CC with a success rate of 63.8% (44/69). The primary features of established PDX tumors, including clinicopathological features, the expression levels of protein biomarkers including Ki67, α-smooth muscle actin, and p16, and genomics, were highly consistent with their PTs. Furthermore, xenograft engraftment was likely influenced by the primary tumor size, the presence of follicular helper T cells and the expression of cell adhesion-related genes in primary tumor tissue. The CC derived PDX models were capable of recapitulating the patient’s response to chemotherapy. In a PDX model, a novel therapeutic strategy, the combination of ACT and neratinib, was shown to effectively inhibit the growth of PDX tumors derived from CC patients with HER2-mutation. Conclusions We established by far the largest PDX biobank with a high engraftment rate for CC that preserves the histopathological and genetic characteristics of patient’s biopsy samples, recapitulates patient’s response to conventional therapy, and is capable of evaluating the efficacy of novel therapeutic modalities for CC.

Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) is a commonly used conductive polymer in organic optoelectronic devices. The conductivity and work function of the PEDOT:PSS are two important parameters that significantly determine the performance of the associated optoelectronic device. Traditionally, some solvents were doped in PEDOT:PSS solution or soaked in PEDOT:PSS film to improve its electrical conductivity, but they damaged the integrity of PEDOT:PSS and reduce the film’s work function. Herein, for the first time, we use femtosecond laser irradiation to modify the electrical conductivity and work function of PEDOT:PSS film. We proposed that the femtosecond laser irradiation could selectively remove the superficial insulative PSS, thereby improving the electrical conductivity of the film. The femtosecond laser-irradiated PEDOT:PSS film was further employed as a hole injection layer within cutting-edge perovskite light-emitting diodes (PeLEDs). A maximum luminosity of 950 cd/m2 was obtained in PeLEDs irradiated by femtosecond laser light in thin films, which is five times higher than that of the controlled device. Moreover, the external quantum efficiency of the devices was also increased from 4.6% to 6.3%. This work paved a cost-effective way to regulate the electrical properties of the PEDOT:PSS film.

With the gradual emergence of trends such as the asynchronous interconnection of power grids and the increasing penetration of renewable energy, the issues of ultra-low-frequency oscillations and low-frequency stability in power grids have become more prominent, posing serious challenges to the safety and stability of systems. The voltage-source converter-based HVDC (VSC-HVDC) interconnection is an effective solution to the frequency stability problems faced by regional power grids. VSC-HVDC can participate in system frequency stability control through a frequency limit controller (FLC). This paper first analyses the basic principles of how VSC-HVDC participates in system frequency stability control. Then, in response to the frequency stability control requirements of the sending and receiving power systems, a droop FLC strategy is designed. Furthermore, a multi-objective optimization method for the parameters of the droop FLC is proposed. Finally, a large-scale electromagnetic transient simulation model of the VSC-HVDC interconnected power system is constructed to verify the effectiveness of the proposed droop FLC method.

Aptamers are nucleic acid sequences that specifically bind with target molecules and are vital to applications such as biosensing, drug development, disease diagnostics, etc. The traditional selection procedure of aptamers is based on the Systematic Evolution of Ligands by an Exponential Enrichment (SELEX) process, which relies on repeating cycles of screening and amplification. With the rapid development of aptamer applications, RNA and XNA aptamers draw more attention than before. But their selection is troublesome due to the necessary reverse transcription and transcription process (RNA) or low efficiency and accuracy of enzymes for amplification (XNA). In light of this, we review the recent advances in aptamer selection methods and give an outlook on future development in a non-SELEX approach, which simplifies the procedure and reduces the experimental costs. We first provide an overview of the traditional SELEX methods mostly designed for screening DNA aptamers to introduce the common tools and methods. Then a section on the current screening methods for RNA and XNA is prepared to demonstrate the efforts put into screening these aptamers and the current difficulties. We further predict that the future trend of aptamer selection lies in non-SELEX methods that do not require nucleic acid amplification. We divide non-SELEX methods into an immobilized format and non-immobilized format and discuss how high-resolution partitioning methods could facilitate the further improvement of selection efficiency and accuracy.

Background: Gland cancer is a high-incidence disease endangering human health, and its early detection and treatment need efficient, accurate and objective intelligent diagnosis methods. In recent years, the advent of machine learning techniques has yielded satisfactory results in the intelligent gland cancer diagnosis based on clinical images, greatly improving the accuracy and efficiency of medical image interpretation while reducing the workload of doctors. The foci of this paper is to review, classify and analyze the intelligent diagnosis methods of imaging gland cancer based on machine learning and deep learning. To start with, the paper presents a brief introduction about some basic imaging principles of multi-modal medical images, such as the commonly used CT, MRI, US, PET, and pathology. In addition, the intelligent diagnosis methods of imaging gland cancer are further classified into supervised learning and weakly-supervised learning. Supervised learning consists of traditional machine learning methods like KNN, SVM, multilayer perceptron, etc. and deep learning methods evolving from CNN, meanwhile, weakly-supervised learning can be further categorized into active learning, semi-supervised learning and transfer learning. The state-of-the-art methods are illustrated with implementation details, including image segmentation, feature extraction, the optimization of classifiers, and their performances are evaluated through indicators like accuracy, precision and sensitivity. To conclude, the challenges and development trend of intelligent diagnosis methods of imaging gland cancer are addressed and discussed.

The time-varying meshing force caused by the transmission characteristics of non-circular gears has an important influence on gear drive wear. The elliptic gear pair of the key core components in combing machine is taken as the research object, and a calculation model of gear wear based on the time-varying meshing force is established by applying Hertz basic theory and Archard wear formula. The meshing stiffness of non-circular gears is solved by using the equivalent tooth number method, and the dynamic meshing force and wear of single tooth profile are analyzed. On this basis, the effects of order and eccentricity on dynamic meshing force and wear of elliptical gears are studied. The results show that the dynamic meshing force and wear of gear surfaces increase with the increase of eccentricity and order of elliptical gears. The time-varying meshing force changes at the junction of single and double tooth meshing zone. The tooth profile wear is close to zero near the pitch circle, and the wear is larger at the root and the crown. It is found that the root wear at the radial of the smallest section curve is significantly larger than that at the radial of the largest section curve. The results provide a theoretical basis for using the modification method to reduce the dynamic meshing force and wear, thus prolonging the life of gears.

Cirrhosis is a liver disease that leads to increased intrahepatic resistance, portal hypertension (PH), and splanchnic hyperemia resulting in ascites, variceal bleeding, and hepatorenal syndrome. Terlipressin, a prodrug that converts to a short half-life vasopressin receptor 1 A (V1a) full agonist [8-Lys]-Vasopressin (LVP), is an intravenous treatment for PH complications, but hyponatremia and ischemic side effects require close monitoring. We developed PHIN-214 which converts into PHIN-156, a more biologically stable V1a partial agonist. PHIN-214 enables once-daily subcutaneous administration without causing ischemia or tissue necrosis and has a 10-fold higher therapeutic index than terlipressin in healthy rats. As V1a partial agonists, PHIN-214 and PHIN-156 exhibited maximum activities of 28 % and 42 % of Arginine vasopressin (AVP), respectively. The potency of PHIN-156 and LVP relative to AVP is comparable for V1a (5.20 and 1.65 nM, respectively) and V1b (102 and 115 nM, respectively) receptors. However, the EC50 of PHIN-156 to the V2 receptor was 26-fold higher than that of LVP, indicating reduced potential for dilutional hyponatremia via V2 agonism compared to terlipressin/LVP. No significant off-target binding to 87 toxicologically relevant receptors were observed when evaluated in vitro at 10 µM concentration. In bile duct ligated rats with PH, subcutaneous PHIN-214 reduced portal pressure by 13.4 % ± 3.4 in 4 h. These collective findings suggest that PHIN-214 could be a novel pharmacological treatment for patients with PH, potentially administered outside of hospital settings, providing a safe and convenient alternative for managing PH and its complications.

This paper proposes a coordinated frequency regulation strategy for grid-forming (GFM) type-4 wind turbine (WT) and energy storage system (ESS) controlled by DC voltage synchronous control (DVSC), where the ESS consists of a battery array, enabling the power balance of WT and ESS hybrid system in both grid-connected (GC) and stand-alone (SA) modes. The newly developed GFM framework, i.e., DVSC, is adopted in both WT and ESS, which utilizes DC voltage dynamics for synchronization purposes. In this paper, the GC mode and SA mode are transferred by changing the status of the series-connected switch, and it is necessary to meet the grid connection conditions when the system is transferred to the GC mode, namely, voltage, frequency, and phase sequence. For the GC mode, the inertia response from WT can be realized using the reserved energy of the DC capacitor, while the ESS serves to eliminate the steady-state frequency deviation and reduce the DC voltage fluctuation of WT using the designed secondary frequency regulation scheme. For the SA mode, the proposed strategy can keep the power balance without external power sources. The small-signal model of the WT and ESS hybrid system is derived. The stability analysis in both GC and SA modes is fully conducted utilizing the modal analysis method, where the impacts of control parameters on stability are assessed. The performance of the proposed strategy in a weak system is evaluated. Simulation studies are carried out under various power system contingencies to verify the effectiveness of the proposed strategy and validate the correctness of the theoretical analysis.

This paper reports a two-step method for preparing a metal-organic framework (MOF) MIL-101 (Fe) based substrate with high sensitivity and stability for surface-enhanced Raman scattering (SERS) analysis. Firstly, MIL-101 (Fe) nanoparticles were synthesized using a traditional solvothermal method. Next, gold nanoparticles (AuNPs) were produced through a reduction method, and the AuNPs/MIL-101 (Fe) composite substrate was created by combining MIL-101 (Fe) with AuNPs. The adsorption capacity of the substrate and its SERS activity after multiple cleaning were tested. Using Rhodamine 6 G (R6G) as the probe molecule, the substrate's detection capability reached 10-8 M, with a relative standard deviation (RSD) of approximately 13.15%, indicating excellent SERS performance and uniformity. The ideal detection capability for sulfapyridine using the composite matrix can be as low as 10-6 M. This proposed substrate is convenient and efficient, holding great potential for the rapid and sensitive detection of antibiotic residues and other environmental pollutants.

ABSTRACTHuman papillomavirus (HPV) has a great impact on world health. Vaccination is among the most important methods of preventing HPV infection. This study investigated Chinese male college students’ knowledge of, attitude toward, and acceptance of the 9vHPV vaccine and the independent predictors. An online cross-sectional study was conducted among male college students at Chinese colleges and universities from March 12 to March 23, 2022. Based on a literature review of similar studies, a self-questionnaire was designed to investigate the students’ knowledge of, attitude toward, and acceptance of the 9vHPV vaccine. Multivariate logistic regression analysis was performed to identify factors influencing their willingness to be vaccinated. In addition, the structural equation model was constructed. A total of 1,547 male college students completed the survey. Of all the students, 54.95% were unwilling to receive a 9vHPV vaccination, while only 45.05% expressed willingness. Multivariate logistic regression analysis revealed that the male college students willing to receive the vaccine included medical students, those in a romantic relationship, those whose relatives and friends had cervical cancer, those whose relatives and friends had received the 9vHPV vaccine, those supportive of promoting the vaccine for men, and those who would recommend the vaccine to their relatives and friends. Male college students exhibited high hesitancy toward the 9vHPV vaccine. Acceptance of the 9vHPV vaccine by male college students can be improved by deepening their accurate understanding of the vaccine and enhancing their positive attitude toward it.

Grouting reinforcement is an effective method for controlling the stability of engineering rock mass. The mechanism is mainly to inject or infiltrate the grout into the fracture of rock mass to form a grouting entity, and strengthen the stability of rock mass and the ability to resist failures. In order to realize the calculation of the whole process of grouting diffusion and consolidation in broken surrounding rock, a diffusion-consolidation mechanism of grouting based on discrete element method was proposed. Also, the model checking and example analysis were carried out, and the results show that: ① In the full-length grouting of single fracture scenario, the shear peak strength of the post-fractured rock mass is higher than that of the non-grouting fracture, which depends on the frictional resistance generated by the solidification and cohesion of the slurry. ② In the point grouting simulation experiment, as the grouting pressure increases, the grout continues to diffuse. Therefore, the pre-peak shear yielding and post-peak phases of the rock mass are strengthened. ③ For the engineering-scale simulation test, as the grouting pressure increases, the diffusion radius increases in two stages. When the grout expands to the high-stress area, it needs to overcome a greater compressive stress to achieve flow. After reaching a relative higher grouting pressure, the diffusion area of adjacent boreholes is superimposed to form a grouting whole body that surrounds the roadway. When the solidification bond strength of the grout is low, the failure of contact is still the main controlling factor to determine the failure and instability of the roadway.

Abstract Partition model (PM) for Y-90 microsphere radioembolization is limited in providing 3D dosimetrics. Voxel-S-Values (VSV) method has good agreement with Monte Carlo (MC) simulations for 3D absorbed dose conversion. We propose a new VSV method and compare its performance along with PM, MC and other VSV methods for Y-90 RE treatment planning based on Tc-99m MAA SPECT/CT. Twenty Tc-99m-MAA SPECT/CT patient data are retrospectively analyzed. Seven VSV methods are implemented: (1) local energy deposition; (2) liver kernel; (3) liver kernel and lung kernel; (4) liver kernel with density correction (LiKD); (5) liver kernel with center voxel scaling (LiCK); (6) liver kernel and lung kernel with density correction (LiLuKD); (7) proposed liver kernel with center voxel scaling and lung kernel with density correction (LiCKLuKD). Mean absorbed dose and maximum injected activity (MIA) obtained by PM and VSV are evaluated against MC results, and 3D dosimetrics generated by VSV are compared with MC. LiKD, LiCK, LiLuKD and LiCKLuKD have the smallest deviation in normal liver and tumors. LiLuKD and LiCKLuKD have the best performance in lungs. MIAs are similar by all methods. LiCKLuKD could provide MIA consistent with PM, and precise 3D dosimetrics for Y-90 RE treatment planning.

Microplastic pollution is a research hotspot around the world. This study investigated the characteristics of microplastic pollution in the freshwater environments of 21 major cities across China. Through indoor and outdoor experimental analysis, we have identified the spatial and temporal distribution characteristics of microplastic pollution in China’s freshwater environments. Our findings indicate that the average concentration of microplastics in China’s freshwater environments is 3502.6 n/m3. The majority of these microplastics are fibrous (42.5%), predominantly smaller than 3 mm (28.1%), and mostly colored (64.7%). The primary chemical components of these microplastics are polyethylene (PE, 33.6%), polyvinyl chloride (PVC, 21.5%), polypropylene (PP, 16.8%), and polystyrene (PS, 15.6%). The abundance of microplastics in China’s freshwater environments generally tends to increase from west to east and from south to north, with the lowest concentration found in Xining, Qinghai (1737.5 n/m3), and the highest in Jiamusi, Heilongjiang (5650.0 n/m3). The distribution characteristics of microplastics are directly related to land use types, primarily concentrated in areas of intense human activity, including agricultural, transport, and urban land. Seasonal changes affect the abundance of microplastics, peaking in summer, followed by spring and autumn, mainly due to variations in rainfall, showing a positive correlation.

The emergence and application of connected and automated vehicles (CAVs) have played a positive role in improving the efficiency of urban transportation and achieving sustainable development. To improve the traffic efficiency at signalized intersections in a connected environment while simultaneously reducing energy consumption and ensuring a more comfortable driving experience, this study investigates a flexible and real-time control method to navigate the CAVs at signalized intersections utilizing reinforcement learning (RL). Initially, control of CAVs at intersections is formulated as a Markov Decision Process (MDP) based on the vehicles’ motion state and the intersection environment. Subsequently, a comprehensive reward function is formulated considering energy consumption, efficiency, comfort, and safety. Then, based on the established environment and the twin delayed deep deterministic policy gradient (TD3) algorithm, a control algorithm for CAVs is designed. Finally, a simulation study is conducted using SUMO, with Lankershim Boulevard as the research scenario. Results indicate that the proposed methods yield a 13.77% reduction in energy consumption and a notable 18.26% decrease in travel time. Vehicles controlled by the proposed method also exhibit smoother driving trajectories.

BackgroundPersonalized dosimetry for Lu-177-PSMA treatment requires multiple-time-point SPECT/CT scans to calculate time-integrated activity (TIA). This study evaluates two-time-point (TTP) methods for TIA calculation for kidneys and tumors.MethodsA total of 18 patients treated with 3.7-7.4 GBq Lu-177 PSMA-617 were analyzed retrospectively, including 18 sets of left and right kidneys, as well as 45 tumors. Four quantitative SPECT/CT (4TP) were acquired at 2 h, 20 h, 40 h, 60 h (n = 11), or 200 h (n = 7) after treatment, and they were fit bi-exponentially as reference. The TTP method was fitted by a mono-exponential washout function using two selected imaging time points for kidneys. For tumors, one uptake and one washout phase were modeled, assuming linear (type I) and same (type II) uptake phase between 0 h to the first time point and mono-exponential washout thereafter. Two single-time-point (STP) methods were also implemented for comparison. TIA calculated by TTP and STP methods were compared with reference to the 4TP TIA.ResultsFor the kidneys, the TTP methods using 20 h-60 h and 40 h-200 h had smaller mean absolute errors of 8.05 ± 6.05% and 4.95 ± 3.98%, respectively, as compared to other combinations of time points and STP methods. For tumors, the type I and type II TTP methods using 20h−60 h and 40–200 h had smaller mean absolute errors of 6.14 ± 5.19% and 12.22 ± 4.44%, and 8.31 ± 7.16% and 4.48 ± 7.10%, respectively, as compared to other TTP and STP methods.ConclusionThe TTP methods based on later imaging time demonstrated fewer errors than the STP methods in kidney and tumor TIA. Imaging at 20 h−60 h and 40 h−200 h could simplify the dosimetry procedures with fewer TIA estimation errors.

Indoor pollutants change over time and place. Exposure to hazardous organics is associated with adverse health effects. This work sampled gaseous organics by Tenax TA tubes in two indoor rooms, i.e., an office set as samples, and the room of chassis dynamometer (RCD) set as backgrounds. Compounds are analyzed by a thermal desorption comprehensive two-dimensional gas chromatography-quadrupole mass spectrometer (TD-GC × GC-qMS). Four new chemicals of emerging concern (CECs) are screened in 469 organics quantified. We proposed a three-step pipeline for CECs screening utilizing GC × GC including 1) non-target scanning of organics with convincing molecular structures and quantification results, 2) statistical analysis between samples and backgrounds to extract useful information, and 3) pixel-based property estimation to evaluate the contamination potential of addressed chemicals. New CECs spotted in this work are all intermediate volatility organic compounds (IVOCs), containing mintketone, isolongifolene, β-funebrene, and (5α)-androstane. Mintketone and sesquiterpenes may be derived from the use of volatile chemical products (VCPs), while (5α)-androstane is probably human-emitted. The occurrence and contamination potential of the addressed new CECs are reported for the first time. Non-target scanning and the measurement of IVOCs are of vital importance to get a full glimpse of indoor organics.

Cells continuously experience and respond to different physical forces that are used to regulate their physiology and functions. Our ability to measure these mechanical cues is essential for understanding the bases of various mechanosensing and mechanotransduction processes. While multiple strategies have been developed to study mechanical forces within two-dimensional (2D) cell culture monolayers, the force measurement at cell-cell junctions in real three-dimensional (3D) cell models is still pretty rare. Considering that in real biological systems, cells are exposed to forces from 3D directions, measuring these molecular forces in their native environment is thus highly critical for the better understanding of different development and disease processes. We have recently developed a type of DNA-based molecular probe for measuring intercellular tensile forces in 2D cell models. Herein, we will report the further development and first-time usage of these molecular tension probes to visualize and detect mechanical forces within 3D spheroids and embryoid bodies (EBs). These probes can spontaneously anchor onto live cell membranes via the attached lipid moieties. By varying the concentrations of these DNA probes and their incubation time, we have first characterized the kinetics and efficiency of probe penetration and loading onto tumor spheroids and stem cell EBs of different sizes. After optimization, we have further imaged and measured E-cadherin-mediated forces in these 3D spheroids and EBs for the first time. Our results indicated that these DNA-based molecular tension probes can be used to study the spatiotemporal distributions of target mechanotransduction processes. These powerful imaging tools may be potentially applied to fill the gap between ongoing research of biomechanics in 2D systems and that in real 3D cell complexes.

The characterization of epigenetic changes during cancer development and progression led to notable insights regarding the roles of cancer-specific epigenetic reprogramming. Recent studies showed that transcription factors (TFs) are capable to regulate epigenetic reprogramming at specific loci in different cancer types through their DNA-binding activities. However, the causal association of dynamic histone modification change mediated by TFs is still not well elucidated. Here we evaluated the impacts of 636 transcription factor binding activities on histone modification in 24 cancer types. We performed Instrumental Variables analysis by using genetic lesions of TFs as our instrumental proxies, which previously discovered to be associated with histone mark activities. As a result, we showed a total of 6 EpiTFs as strong directors of epigenetic reprogramming of histone modification in cancers, which alters the molecular and clinical phenotypes of cancer. Together our findings highlight a causal mechanism driven by the TFs and genome-wide histone modification, which is relevant to multiple status of oncogenesis.