Search

Abstract Background The log odds of positive lymph nodes (LODDS) was considered a superior staging system to N stage in colon cancer, yet its value in determining the optimal duration of adjuvant chemotherapy for stage III colon cancer patients has not been evaluated. This study aims to assess the prognostic value of a model that combines LODDS with clinicopathological information for stage III colon cancer patients and aims to stratify these patients using the model, identifying individuals who could benefit from varying durations of adjuvant chemotherapy. Method A total of 663 consecutive patients diagnosed with stage III colon cancer, who underwent colon tumor resection between November 2007 and June 2020 at Sun Yat-sen University Cancer Center and Longyan First Affiliated Hospital of Fujian Medical University, were enrolled in this study. Survival outcomes were analyzed using Kaplan–Meier, Cox regression. Nomograms were developed to forecast patient DFS, with the Area Under the Curve (AUC) values of time-dependent Receiver Operating Characteristic (timeROC) and calibration plots utilized to assess the accuracy and reliability of the nomograms. Results Multivariate analysis revealed that perineural invasion (HR = 1.776, 95% CI: 1.052–3.003, P = 0.032), poor tumor differentiation (HR = 1.638, 95% CI: 1.084–2.475, P = 0.019), and LODDS groupings of 2 and 1 (HR = 1.920, 95% CI: 1.297–2.842, P = 0.001) were independent predictors of disease-free survival (DFS) in the training cohort. Nomograms constructed from LODDS, perineural invasion, and poor tumor differentiation demonstrated robust predictive performance for 3-year and 5-year DFS in both training (3-year AUC = 0.706, 5-year AUC = 0.678) and validation cohorts (3-year AUC = 0.744, 5-year AUC = 0.762). Stratification according to this model showed that patients in the high-risk group derived significant benefit from completing 8 cycles of chemotherapy (training cohort, 82.97% vs 67.17%, P = 0.013; validation cohort, 89.49% vs 63.97%, P = 0.030). Conclusion The prognostic model, integrating LODDS, pathological differentiation, and neural invasion, demonstrates strong predictive accuracy for stage III colon cancer prognosis. Moreover, stratification via this model offers valuable insights into optimal durations of postoperative adjuvant chemotherapy.

Atherosclerosis is a severe cardiovascular disease followed by the accumulation of atherosclerotic plaques within the lumen of blood vessels resulting in reduced blood flow thus initiating a series of events. Conventional therapies for atherosclerosis encounter multiple challenges, especially difficulty in precisely concentrating in certain affected regions and the potential for unwanted side effects. Consequently, scientists are focused on developing nanoformulations for atherosclerosis diagnosis and therapy. Peptide-based nanomedicines improve conventional therapies by offering improved structural and therapeutic stability and enabling target-specific delivery. Their inherent biocompatibility and biodegradability additionally render them desirable materials intended for in vivo use. This review manuscript aims to provide an in-depth overview of peptide-based nanomedicines for atherosclerosis, focusing on targeted cells like endothelial cells, macrophages, and monocytes and their interaction with different plaque components. Moreover, the manuscript also highlights the latest progress in multimodal techniques and provides a comprehensive overview of limitations associated with their practical implementation.

Abstract Background Prostate cancer (PCa) is a leading cause of cancer-related death in men. Understanding the proteomic landscape associated with PCa risk can provide insights into its molecular mechanisms and pave the way for potential therapeutic interventions. Methods A proteome-wide Mendelian randomization (MR) analysis was employed to determine associations between genetically predicted protein concentrations in plasma and PCa risk. From an initial list of 4,364 proteins, significant associations were identified and validated. Multiple sensitivity analyses were also conducted to enhance the robustness of our findings. Results Of the 4,364 genetically predicted proteins, 308 exhibited preliminary associations with PCa risk. After rigorous statistical refinement, genetically predicted concentrations of 14 proteins showed positive associations with PCa risk, with odds ratios spanning from 1.55 (95% CI 1.28–1.87) for ATG4B to 2.67 (95% CI 1.94–3.67) for HCN1. In contrast, genetically predicted concentrations of ATG7, B2M, MSMB, and TMEM108 demonstrated inverse associations with PCa. The replication analysis further substantiated positive associations for MDH1 and LSM1, and a negative one for MSMB with PCa. A meta-analysis harmonizing primary and replication data mirrored these findings. Furthermore, the MVMR analysis pinpointed B2M and MSMB as having significant associations with PCa risk. Conclusion The genetic evidence unveils a refined set of proteins associated with PCa risk. The findings underscore the potential of these proteins as molecular markers or therapeutic targets for PCa, calling for deeper mechanistic studies and exploration into their translational relevance.

Abstract To eliminate blind spots in the field of vision and achieve a safe and collision‐free path, this paper proposes a path planning method based on multivehicle collaborative mapping in the context of vehicle networking. First, a multi vehicle map merging strategy based on the fireworks algorithm is proposed. In this strategy, a dissimilarity objective function based on the concept of grid map similarity is established and an improved fireworks algorithm is used to quickly search for the maximum overlap between local maps, achieving multivehicle collaborative mapping. Second, a real‐time path planning method based on artificial potential field theory is proposed. The information obtained from multivehicle collaborative mapping is first combined with the potential field model to form a multifield coupled road environment model. Then, the obstacle repulsion potential field model is improved to address the issues of traditional artificial potential field methods that target unreachability and poor dynamic response. The feasibility and effectiveness of the collaborative path planning method and single vehicle path planning method are tested through simulation analysis. This paper demonstrates through simulation analysis that the proposed path planning method can effectively achieve beyond line of sight perception and safely and comfortably guide vehicles to complete path planning.

【Objective】Deqing County, Guangdong Province is a native habitat of Morinda officinalis How., a genuine medicinal herb in China. In the study, the genetic diversity of germplasm resources of 24 varieties of Morinda officinalis How. were analyzed.【Method】A total of 24 Morinda officinalis How. resources collected from Deqing County as research objects, and principal component analysis and molecular marker methods (SRAP and CDD) were used to analyze the genetic diversity of 24 Morinda officinalis How. materials.【Result】Phenotypic analysis showed that, in the cluster map based on principal component analysis, Guanwei Town, Gaoliang Town, Fengcun Town and Gaoliang Town were clustered in four groups. In addition, 100 and 98 total bands were obtained in 18 pairs of SRAP primer combinations and 16 CDDP primers, among them, there were 50 SRAP polymorphic bands, resulting in a polymorphism ratio of 50%. The average genetic similarity coefficient (GS) was 0.87, and the GS ranged from 0.71 to 0.97. There were 80 polymorphic bands in CDDP, with a polymorphism ratio of 79.0%. The GS among germplasm resources ranged from 0.71 to 0.96, with an average (GS) of 0.86. When the coefficient was 0.82, both SRAP and CDDP molecular markers showed certain similarities among the germplasm resources of Gaoliang Town, Guanxu Town and Fengcun Town.【Conclusion】Combined with the clustering results of phenotypic and molecular marker, the genetic relationship is closest between Gaoliang Town and Guanwei Town as well as Gaoliang Town and Fengcun Town. The results of SRAP and CDDP molecular marker methods have certain differences in the genetic diversity of Morinda officinalis How., and the combined analysis can better reflect the genetic diversity of Morinda officinalis How. and the phylogenetic relationship of Morinda officinalis How. resources.

Abstract Online rumors are widespread and difficult to identify, which bring serious harm to society and individuals. To effectively detect and govern online rumors, it is necessary to conduct in-depth semantic analysis and understand the content features of rumors. This paper proposes a TFI domain ontology construction method, which aims to achieve semantic parsing and reasoning of the rumor text content. This paper starts from the term layer, the frame layer, and the instance layer, and based on the reuse of the top-level ontology, the extraction of core literature content features, and the discovery of new concepts in the real corpus, obtains the core classes (five parent classes and 88 subclasses) of the rumor domain ontology and defines their concept hierarchy. Object properties and data properties are designed to describe relationships between entities or their features, and the instance layer is created according to the real rumor datasets. OWL language is used to encode the ontology, Protégé is used to visualize it, and SWRL rules and pellet reasoner are used to mine and verify implicit knowledge of the ontology, and judge the category of rumor text. This paper constructs a rumor domain ontology with high consistency and reliability.

Abstract. Background:. Arterial stiffening increases with age and blood pressure and is associated with cardiovascular disease (CVD), but the relationship between blood pressure lowering and arterial stiffening is still uncertain, especially in older people. This study aimed to evaluate the effect of intensive blood pressure treatment on the progression of arterial stiffness and risk of CVD in older patients with hypertension. Methods:. The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial was a multicenter, randomized, controlled trial performed at 42 clinical centers throughout China, and 8511 patients aged 60–80 years with essential hypertension were enrolled and randomly assigned to systolic blood pressure (SBP) target of 110 mmHg to

Background: Postmenopausal osteoporosis (PMOP) represents as a significant health concern, particularly as the population ages. Currently, there is a paucity of comprehensive descriptions regarding the immunoregulatory mechanisms and early diagnostic biomarkers associated with PMOP. This study aims to examine immune-related differentially expressed genes (IR-DEGs) in the peripheral blood mononuclear cells of PMOP patients to identify immunological patterns and diagnostic biomarkers. Methods: The GSE56815 dataset from the Gene Expression Omnibus (GEO) database was used as the training group, while the GSE2208 dataset served as the validation group. Initially, differential expression analysis was conducted after data integration to identify IR-DEGs in the peripheral blood mononuclear cells of PMOP. Subsequently, feature selection of these IR-DEGs was performed using RF, SVM-RFE, and LASSO regression models. Additionally, the expression of IR-DEGs in distinct bone marrow cell subtypes was analyzed using single-cell RNA sequencing (scRNA-seq) datasets, allowing the identification of cellular communication patterns within various cell subgroups. Finally, molecular subtypes and diagnostic models for PMOP were constructed based on these selected IR-DEGs. Furthermore, the expression levels of characteristic IR-DEGs were examined in rat osteoporosis (OP) models. Results: Using machine learning, six IR-DEGs (JUN, HMOX1, CYSLTR2, TNFSF8, IL1R2, and SSTR5) were identified. Subsequently, two molecular subtypes of PMOP (subtype 1 and subtype 2) were established, with subtype 1 exhibiting a higher proportion of M1 macrophage infiltration. Analysis of the scRNA-seq dataset revealed 11 distinct cell clusters. It was noted that JUN was significantly overexpressed in M1 macrophages, while HMOX1 showed a marked elevation in endothelial cells and M2 macrophages. Cell communication results suggested that the PMOP microenvironment features increased interactions among M2 macrophages, CD8+ T cells, Tregs, and fibroblasts. The diagnostic model based on these six IR-DEGs demonstrated excellent diagnostic performance (AUC = 0.927). In the OP rat model, the expression of IL1R2 and TNFSF8 were significantly elevated. Conclusion: JUN, HMOX1, CYSLTR2, TNFSF8, IL1R2, and SSTR5 may serve as promising molecular targets for diagnosing and subtyping patients with PMOP. These results offer novel perspectives on the early diagnosis of PMOP and the advancement of personalized immune-based therapies.

Abstract Background Elizabethkingia is emerging as an opportunistic pathogen in humans. The aim of this study was to investigate the clinical epidemiology, antimicrobial susceptibility, virulence factors, and genome features of Elizabethkingia spp. Methods Clinical data from 71 patients who were diagnosed with Elizabethkingia-induced pneumonia and bacteremia between August 2019 and September 2021 were analyzed. Whole-genome sequencing was performed on seven isolates, and the results were compared with a dataset of 83 available Elizabethkingia genomes. Genomic features, Kyoto Encyclopedia of Genes and Genomes (KEGG) results and clusters of orthologous groups (COGs) were analyzed. Results The mean age of the patients was 56.9 ± 20.7 years, and the in-hospital mortality rate was 29.6% (21/71). Elizabethkingia strains were obtained mainly from intensive care units (36.6%, 26/71) and emergency departments (32.4%, 23/71). The majority of the strains were isolated from respiratory tract specimens (85.9%, 61/71). All patients had a history of broad-spectrum antimicrobial exposure. Hospitalization for invasive mechanical ventilation or catheter insertion was found to be a risk factor for infection. The isolates displayed a high rate of resistance to cephalosporins and carbapenems, but all were susceptible to minocycline and colistin. Genomic analysis identified five β-lactamase genes (bla GOB, bla BlaB, bla CME, bla OXA, and bla TEM) responsible for β-lactam resistance and virulence genes involved in stress adaptation (ureB/G, katA/B, and clpP), adherence (groEL, tufA, and htpB) and immune modulation (gmd, tviB, cps4J, wbtIL, cap8E/D/G, and rfbC). Functional analysis of the COGs revealed that “metabolism” constituted the largest category within the core genome, while “information storage and processing” was predominant in both the accessory and unique genomes. The unique genes in our 7 strains were mostly enriched in KEGG pathways related to microRNAs in cancer, drug resistance (β-lactam and vancomycin), ABC transporters, biological metabolism and biosynthesis, and nucleotide excision repair mechanisms. Conclusion The Elizabethkingia genus exhibits multidrug resistance and carries carbapenemase genes. This study presents a comparative genomic analysis of Elizabethkingia, providing knowledge that facilitates a better understanding of this microorganism.

Abstract Danmakus are user-generated comments that overlay on videos, enabling real-time interactions between viewers and video content. The emotional orientation of danmakus can reflect the attitudes and opinions of viewers on video segments, which can help video platforms optimize video content recommendation and evaluate users’ abnormal emotion levels. Aiming at the problems of low transferability of traditional sentiment analysis methods in the danmaku domain, low accuracy of danmaku text segmentation, poor consistency of sentiment annotation, and insufficient semantic feature extraction, this paper proposes a video danmaku sentiment analysis method based on MIBE-RoBERTa-FF-BiLSTM. This paper constructs a “Bilibili Must-Watch List and Top Video Danmaku Sentiment Dataset” by ourselves, covering 10,000 positive and negative sentiment danmaku texts of 18 themes. A new word recognition algorithm based on mutual information (MI) and branch entropy (BE) is used to discover 2610 irregular network popular new words from trigrams to heptagrams in the dataset, forming a domain lexicon. The Maslow’s hierarchy of needs theory is applied to guide the consistent sentiment annotation. The domain lexicon is integrated into the feature fusion layer of the RoBERTa-FF-BiLSTM model to fully learn the semantic features of word information, character information, and context information of danmaku texts and perform sentiment classification. Comparative experiments on the dataset show that the model proposed in this paper has the best comprehensive performance among the mainstream models for video danmaku text sentiment classification, with an F1 value of 94.06%, and its accuracy and robustness are also better than other models. The limitations of this paper are that the construction of the domain lexicon still requires manual participation and review, the semantic information of danmaku video content and the positive case preference are ignored.

Introduction: DNA ploidy (P), stroma fraction (S), and nucleotyping (N) collectively known as PSN, have proven prognostic accuracy in stage II colorectal cancer (CRC). However, few studies have reported on the prognostic value of the PSN panel in stage III colon cancer patients receiving capecitabine and oxaliplatin adjuvant chemotherapy. Objectives: This study aimed to validate PSN’s prognostic impact on stage III colon cancer, identifying candidates for optimized adjuvant chemotherapy duration. Design: A retrospective analysis was conducted on a cohort of stage III colon cancer patients from April 2008 to June 2020. Methods: Postoperative pathological samples from stage III colon cancer patients who underwent radical surgery and postoperative adjuvant chemotherapy at Sun Yat-sen University Cancer Center were retrospectively collected. Automated digital imaging assessed PSN, categorizing risk groups. Kaplan–Meier, Cox regression, and time-dependent receiver operating characteristic analysis compared model validity. Results: Significant differences in 5-year disease-free survival (DFS) and overall survival (OS) were noted among PSN-based low-, moderate-, and high-risk groups (DFS: 92.10% versus 83.62% versus 79.80%, p = 0.029; OS: 96.69% versus 93.99% versus 90.12%, p = 0.016). PSN emerged as an independent prognostic factor for DFS [hazard ratio (HR) = 1.409, 95% confidence interval (CI): 1.002–1.981, p = 0.049] and OS (HR = 1.720, 95% CI: 1.127–2.624, p = 0.012). The PSN model, incorporating perineural invasion and tumor location, displayed superior area under the curve for 5-year (0.692 versus 0.553, p = 0.020) and 10-year (0.694 versus 0.532, p = 0.006) DFS than TNM stage. In the PSN high-risk group, completing eight cycles of adjuvant chemotherapy significantly improved 5-year DFS and OS compared to four to seven cycles (DFS: 89.43% versus 71.52%, p = 0.026; OS: 96.77% versus 85.46%, p = 0.007). Conclusion: The PSN panel effectively stratifies stage III colon cancer, aiding in optimized adjuvant chemotherapy duration determination.

Rumor governance is an important guarantee for social stability and public safety. Based on the life cycle and crisis cycle model, this paper conducts a synergistic analysis of China's rumor governance policies and regulations and the core scientific research literature on rumor governance in WOS and CNKI. In this paper, we use the TF-IDF algorithm to count the word frequencies of 326 policy and regulation texts, the Jieba-RoBERTa-Kmeans model to cluster high-frequency keywords, and CiteSpace software and the LLR clustering algorithm are utilized to extract and cluster keywords from 391 documents in the WOS database and from 703 documents in the CNKI database. Based on the synergistic analysis of the life cycle model, it is found that the research on policies and regulations precedes the research on literature, and both are in the period of refinement.Based on the synergistic analysis using the co-occurrence comparison of subject terms in the crisis cycle model, it is found that there is a lack of research in the stages of prevention, monitoring, and governance, and this paper proposes the systematic governance mechanism and strategy for crisis resolution that conforms to the trend of life cycle evolution and is synergistic with policy and literature. This study has only selected Chinese policies and regulations, and the proposed governance strategies have not yet been verified in practice; future research can expand the scope and depth of the study and conduct empirical research and pilot projects.

Enhancement of farming management relies heavily on enhancing farmer knowledge. In the past, both the direct learning approach and the personnel extension system for improving fertilization practices of smallholders has proven insufficiently effective. Therefore, this article proposes an interactive knowledge learning approach using artificial intelligence as a promising alternative. The system consists of two parts. The first is a dialog interface that accepts information from farmers about their current farming practices. The second part is an intelligent decision system, which categorizes the information provided by farmers in two categories. The first consists of on-farm constraints, such as fertilizer resources, split application times and seasons. The second comprises knowledge-based practices by farmers, such as nutrient in- and output balance, ratios of different nutrients and the ratios of each split nutrient amount to the total nutrient input. The interactive knowledge learning approach aims to identify and rectify incorrect practices in the knowledge-based category while considering the farmer’s available finance, labor, and fertilizer resources. Investigations show that the interactive knowledge learning approach can make a strong contribution to prevention of the overuse of nitrogen and phosphorus fertilizers, and mitigating agricultural non-point source pollution.

Abstract Background Liver metastasis is the leading cause of death in patients with colorectal cancer (CRC). Emerge evidence suggests that circular RNA (circRNA) is a pivotal player in cancer progression. However, its role in CRC liver metastasis remains largely unknown. Methods Circ-YAP expression was detected by qRT-PCR and in situ hybridization. The function of circ-YAP was tested by wound healing, transwell and CCK-8 assays. RNA immunoprecipitation, pull-down, luciferase reporter, chromatin immunoprecipitation assays were used to investigate the mechanism underlying circ-YAP promoting CRC liver metastasis. CRC liver metastasis animal model was established to assess the effect of circ-YAP in vivo. Results Circ-YAP was notably upregulated in CRC with liver metastasis, which was associated with dismal prognosis. Circ-YAP promoted CRC cell migration and invasion in vitro, and facilitated liver metastasis in patient-derived xenografts (PDX) models in vivo. Mechanistically, circ-YAP encoded a novel truncated protein containing 220 amino acids, termed as YAP-220aa, which competitively bound to LATS1, resulting in YAP dephosphorylation and nuclear translocation, thereby activating a cohort of metastasis-promoting genes. Importantly, N6-methyladenosine (m6A) modification orchestrated efficient initiation of circ-YAP translation, requiring m6A reader YTHDF3 and eIF4G2 translation initiation complex. Intriguingly, circ-YAP was transcriptionally enhanced by YAP/TEAD complex, thus forming a positive regulatory feed-forward loop. Conclusions Our findings reveal a previously uncharacterized oncoprotein encoded by circ-YAP, implying a promising biomarker and therapeutic target for CRC patients with liver metastasis.

Abstract Neutrophil extracellular traps (NETs) have been categorized as a form of inflammatory cell death mode of neutrophils (NETosis) involved in natural immunity and the regulation of adaptive immunity. More and more studies revealed the ability of NETs to reshape the tumor immune microenvironment (TIME) by limiting antitumor effector cells, which may impair the efficacy of immunotherapy. To explore whether NETs-related genes make vital impacts on Colon carcinoma (COAD), we have carried out a systematic analysis and showed several findings in the present work. First, we obtained the patient's data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) dataset, aiming to detect two NETs-associated subtypes by consensus clustering. For the purpose of annotating the roles of NETs-related pathways, gene ontology enrichment analyses were adopted. Next, we constructed a 6 novel NETs-related genes score using the Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model. We found that the NETs risk score was notably upregulated in COAD patient samples, and its levels were notably correlated with tumor clinicopathological and immune traits. Then, according to NETs-associated molecular subtypes and the risk signature, this study compared immune cell infiltration calculated through the estimate, CIBERSORT, TIMER, ssGSEA algorithms, tumor immune dysfunction, as well as exclusion (TIDE). Furthermore, we confirm that MPO(myeloperoxidase) was significantly upregulated in COAD patient samples, and its levels were significantly linked to tumor malignancy and clinic outcome. Moreover, multiplex immunohistochemistry (mIHC) spatial analysis confirmed that MPO was closely related to Treg and PD-1 + Treg in spatial location which suggested MPO may paly an important role in TIME formation. Altogether, the obtained results indicated that a six NETs-related genes prognostic signature was conducive to estimating the prognosis and response of chemo-/immuno-therapy of COAD patients.

IntroductionAge-related macular degeneration (AMD) is a prevalent, chronic and progressive retinal degenerative disease characterized by an inflammatory response mediated by activated microglia accumulating in the retina. In this study, we demonstrate the therapeutically effects and the underlying mechanisms of microglial repopulation in the laser-induced choroidal neovascularization (CNV) model of exudative AMD.MethodsThe CSF1R inhibitor PLX3397 was used to establish a treatment paradigm for microglial repopulation in the retina. Neovascular leakage and neovascular area were examined by fundus fluorescein angiography (FFA) and immunostaining of whole-mount RPE-choroid-sclera complexes in CNV mice receiving PLX3397. Altered cellular senescence was measured by beta-galactosidase (SA-β-gal) activity and p16INK4a expression. The effect and mechanisms of repopulated microglia on leukocyte infiltration and the inflammatory response in CNV lesions were analyzed.ResultsWe showed that ten days of the CSF1R inhibitor PLX3397 treatment followed by 11 days of drug withdrawal was sufficient to stimulate rapid repopulation of the retina with new microglia. Microglial repopulation attenuated pathological choroid neovascularization and dampened cellular senescence in CNV lesions. Repopulating microglia exhibited lower levels of activation markers, enhanced phagocytic function and produced fewer cytokines involved in the immune response, thereby ameliorating leukocyte infiltration and attenuating the inflammatory response in CNV lesions.DiscussionThe microglial repopulation described herein are therefore a promising strategy for restricting inflammation and choroidal neovascularization, which are important players in the pathophysiology of AMD.

Existing studies revealed high clonal diversity among Staphylococcus aureus bacteremia isolates, especially for methicillin-sensitive S. aureus (MSSA) strains. A 66-year-old male patient presenting with a widespread methicillin-sensitive Staphylococcus aureus (MSSA) infection, accompanied by concurrent carbapenem-resistant Klebsiella pneumoniae (CRKP) bloodstream infection.To evaluate the evolution of the present isolate, whole genome sequencing and bioinformatics analysis were performed for all available MSSA isolates. This patient recovered eventually through drainage and antibiotics combination. Therefore, the virulence factors of MSSA, as the primary pathogenicity, led to widely disseminated infection. The appropriate initial treatment is a major concern after culture identification.

Abstract Clear cell renal cell carcinoma (CCRCC) is a common tumor of the urological system for which surgery is the preferred treatment, but there is a lack of therapeutic options after surgery. This study aims to explore the biological role of GNG7 on CCRCC from a genetic perspective. Differences in mRNA expression and patient survival of GNG7 in patients with CCRCC and healthy patients were analyzed using the TCGA database. It was observed that GNG7 gene expression was downregulated in CCRCC tissue compared with healthy tissue, and high GNG7 predicted better prognosis for patients, and GNG7 also showed strong variability in clinical and TMN staging. The immune relevance of GNG7 and related genes was explored using renal cancer data from CCLE and TISIDB database. It was verified that the risk score constructed by 7 GNG7-related regulators might be used as an independent prognostic risk factor for CCRCC. A CCRCC prognostic model that involved 7 immune genes was further established to predict the survival probabilities of patients. At last, the GEO database and immunochemical tissue staining were used to validate GNG7 expression in CCRCC. Our study proposed a novel panel of genes to predict CCRCC OS based on GNG7-related immune genes, which may help to accurately predict the prognosis of CCRCC patients and make better clinical decisions for individual treatment.

Abstract Background Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has revolutionized microbial identification. However, there is a lack of data on its performance in identifying filamentous fungi. The objective of our study was to evaluate the accuracy of the Autof ms1000 mass spectrometry for identifying filamentous fungi in the clinical microbiology laboratory. Results Among 106 samples tested using the Autof ms1000 system, 101 (95.28%) were identified at the genus or species level, and 81 (76.41%) were accurately identified at the species level. Additionally, we developed a new rapid formic acid extraction method with simple pretreatment for filamentous fungi that saved time and provided accurate results. Conclusions The Autof ms1000 mass spectrometer proved to be a valuable tool for identifying filamentous fungi. However, upgrading the database is recommended for correctly identifying rare strains.

Sandalwood essential oil, known for its rich content of phenolic and flavonoid compounds, holds great promise for applications in perfumery and medicine. However, traditional production methods have raised concerns regarding their environmental impact and sustainability. This study explored subcritical ethanol extraction as a green technique to address these concerns. Under optimized conditions (6.04 MPa, 109 °C, and 2.01 mL/min), maximum oil yield reached 4.04% with substantial total phenolic compounds (TPCs) of 4.11 mg GAE/100 g and total flavonoid compounds (TFCs) of 8.85 mg QE/100 g in the extracted sandalwood oil. Furthermore, the oil displayed notable antioxidant activity AA of 71.68%. The temperature was identified as a significant factor affecting oil yield, TPCs, TFCs, and AA. The fine-tuning of the extraction temperature enhanced the desired characteristics, improving bioactive compound yields and heightening antioxidant potential. This study uses a green extraction technique to contribute to sustainable sandalwood essential oil production.

Abstract Leukemia is a group of highly heterogeneous and life‐threatening blood cancers that originate from abnormal hematopoietic stem cells. Multiple treatments are approved for leukemia, including chemotherapy, targeted therapy, hematopoietic stem cell transplantation, radiation therapy, and immunotherapy. Unfortunately, therapeutic resistance occurs in a substantial proportion of patients and greatly compromises the treatment efficacy of leukemia, resulting in relapse and mortality. The abnormal activity of receptor tyrosine kinases, cell membrane transporters, intracellular signal transducers, transcription factors, and anti‐apoptotic proteins have been shown to contribute to the emergence of therapeutic resistance. Despite these findings, the exact mechanisms of treatment resistance are still not fully understood, which limits the development of effective measures to overcome it. Long non‐coding RNAs (lncRNA) are a class of regulatory molecules that are gaining increasing attention, and lncRNA‐mediated regulation of therapeutic resistance against multiple drugs for leukemia is being revealed. These dysregulated lncRNAs not only serve as potential targets to reduce resistance but also might improve treatment response prediction and individualized treatment decision. Here, we summarize the recent findings on lncRNA‐mediated regulation of therapeutic resistance in leukemia and discuss future perspectives on how to make use of the dysregulated lncRNAs in leukemia to improve treatment outcome.

To facilitate accurate prediction and empirical research on regional agricultural carbon emissions, this paper uses the LLE-PSO-XGBoost carbon emission model, which combines the Local Linear Embedding (LLE), Particle Swarm Algorithm (PSO) and Extreme Gradient Boosting Algorithm (XGBoost), to forecast regional agricultural carbon emissions in Anhui Province under different scenarios. The results show that the regional agricultural carbon emissions in Anhui Province generally show an upward and then downward trend during 2000-2021, and the regional agricultural carbon emissions in Anhui Province in 2030 are expected to fluctuate between 11,342,100 tones and 14,445,700 tones under five different set scenarios. The projections of regional agricultural carbon emissions can play an important role in supporting the development of local regional agriculture, helping to guide the input and policy guidance of local rural low-carbon agriculture and promoting the development of rural areas towards a resource-saving and environment-friendly society.

With the rapid development of social media, new opportunities have been provided for the generation and dissemination of online rumors, making systematic study of rumor detection of great significance for the control and governance of internet rumors. Addressing the limitations of past review studies on rumor detection which were characterized by a single perspective, reliance on subjective judgment, and lack of technological evolution theory, this paper reviews 983 rumor detection articles in the SCI-EXPANDED, SSCI, CPCI-S, CPCI-SSH, CCR-EXPANDED, and IC databases of the Web of Science. Utilizing Citespace and VOSviewer for visual analysis of the articles, and adopting bibliometric theories like network analysis and topic evolution analysis, this study identifies core research groups in the field of rumor detection based on author collaboration network and institution collaboration network. Through high-frequency keyword clustering graph and keyword co-occurrence graph, the study unveils topic associations and cluster structures among keywords, explicates research hotspots in the field of rumor detection, and conducts a fine-grained critical comparative analysis. According to keyword time graph, keyword bursts table, and trends in the number of publications in hot technology fields, combined with the S-curve technology evolution theory, the study discerns the life cycle and research trends of technologies in the rumor detection field. Compared to existing literature reviews, this paper is the first to propose integrating bibliometrics and S-curve technology evolution theory to reveal the state of relevant technologies and research frontiers.

Aqueous electrolytes offer superior prospects for advanced energy storage. “Water-in-salt” (WIS) electrolytes exhibit a wide electrochemical stability window (ESW), but their low conductivity, high viscosity, and precipitation at low temperatures restrict their application. Herein, we report a novel localized “water-in-pyrrolidinium chloride” electrolyte (LWIP; 1 ​mol/L, N-propyl-N-methylpyrrolidinium chloride/(water and N,N-dimethylformamide, 1:4 by molality)) enabling high-voltage, low-temperature supercapacitors (SCs). The greatly improved ESW (3.451 ​V) is mainly attributed to the strong solvation between Cl− and water molecules, which broadens the negative stability. This water-binding mechanism is very different from that of a WIS electrolyte based on alkali metal salt. SCs using LWIP electrolytes not only yield a high operating voltage of 2.4 ​V and excellent capacity retention (82.8% after 15,000 cycles at 5 ​A ​g−1) but also operate stably at −20 ​°C. This work provides new approaches for the design and preparation of novel electrolytes.

Deep eutectic solvents (DES) doping is an important method to realize the preparation and modification of PEDOT:PSS films in aqueous solution, but there is no systematic research focusing on its action mechanism in polymerization process. A series of in-situ characterizations were conducted to investigate the effect of DES doping on properties and structure. The UV–Vis spectra indicated the DES doping can strengthen the π−π* stacking interaction and conjugation stabilization of PEDOT:PSS, and then lead to stronger photovoltaic conversion ability. The in situ FTIR spectra revealed the hydrogen bonds were incorporated into the polymer chain during polymerization process. The CV and SEM analysis results suggested that DES doping delayed passivation nucleation stage of PEDOT:PSS film in the thickness direction and remained a stable polymerization rate. The XPS spectra of S 2p proved DES doping decrease the interaction between PEDOT and PSS. Comprehensive experiments demonstrate that the structure-induced effects of DES can trigger structural reorganization in line conformation of PEDOT:PSS/DESs. It is structure-induced effects of DES that delays passivation nucleation stage in polymerization and improves the optical absorption contrast, maximum current density and some other properties efficently.

Summary: Background: Pegmolesatide, a synthetic peptide-based erythropoietin (EPO) receptor agonist, is being evaluated as an alternative to epoetin alfa for treating anemia of chronic kidney disease (CKD) in Chinese dialysis patients. There is a critical need for a long-acting, cost-effective erythropoiesis-stimulating agent that does not produce EPO antibodies. Methods: A randomized, open-label, active-comparator, non-inferiority phase three trial was conducted at 43 dialysis centers in China between May 17th, 2019, and March 28th, 2022. Eligible patients aged 18–70 years were randomly assigned (2:1) to receive pegmolesatide once every four weeks or epoetin alfa one to three times per week, with doses adjusted to maintain a hemoglobin level between 10.0 and 12.0 g/dL. The primary efficacy endpoint was the mean change in hemoglobin level from baseline to the efficacy evaluation period in the per-protocol set (PPS) population. Non-inferiority of pegmolesatide to epoetin alfa was established if the lower limit of the two-sided 95% confidence interval for the between-group difference was ≥ −1.0 g/dL. Safety assessment included adverse events and potential anaphylaxis reactions. This trial is registered at ClinicalTrials.gov, NCT03902691. Findings: Three hundreds and seventy-two patients were randomly assigned to the pegmolesatide group (248 patients) or the epoetin alfa group (124 patients). A total of 347 patients (233 in the pegmolesatide group and 114 in the epoetin alfa group) were included in the PPS population. In the PPS, the mean change (standard deviation, SD) in hemoglobin level from baseline to the efficacy evaluation period was 0.07 (0.92) g/dL in the pegmolesatide group and −0.22 (0.97) g/dL in the epoetin alfa group. The between-group difference was 0.29 g/dL (95% confidence interval: 0.11–0.47), verifying non-inferiority of pegmolesatide to epoetin alfa. Adverse events occurred in 231 (94%) participants in the pegmolesatide group and in 110 (89%) in the epoetin alfa group. Hypertension was the most common treatment-related adverse event. No fatal cases of anaphylaxis or hypotension were reported. Interpretation: Monthly subcutaneously injection of pegmolesatide was as effective and safe as conventional epoetin alfa administrated one to three times a week in treating anemia in Chinese dialysis patients. Funding: The study was supported by Hansoh Medical Development Group.

Plasmonic vortices confining orbital angular momentums to surface have aroused wide research interest in the last decade. Recent advances of near-field microscopes have enabled the study on the spatiotemporal dynamics of plasmonic vortices, providing a better understanding of optical orbital angular momentums in the evanescent wave regime. However, these works only focused on the objective characterization of plasmonic vortex and have not achieved subjectively tailoring of its spatiotemporal dynamics for specific applications. Herein, it is demonstrated that the plasmonic vortices with the same topological charge can be endowed with distinct spatiotemporal dynamics by simply changing the coupler design. Based on a near-field scanning terahertz microscopy, the surface plasmon fields are directly obtained with ultrahigh spatiotemporal resolution, experimentally exhibiting the generation and evolution divergences during the whole lifetime of plasmonic vortices. The proposed strategy is straightforward and universal, which can be readily applied into visible or infrared frequencies, facilitating the development of plasmonic vortex related researches and applications.

【Objective】In regard to the problems including excessive chemical fertilizer application and serious soil quality decline in litchi orchards in Guangdong Province, and the urgent need of resource utilization of manure produced by the surrounding large-scale livestock and poultry breeding, the effects of fertilizer reduction combined with organic fertilizer on growth and rhizosphere microorganisms of litchi were studied, aiming to provide fertilization references for the scientific planting of litchi in Guangdong Province.【Method】'Guiwei' litchi was used as the research material. Six treatments were set: no fertilization (CK), chemical fertilizer application (CF), fertilizer reduction by 30%, and combined application of pig manure organic fertilizer of 5 kg/plant (OF5), 10 kg/plant (OF10), 15 kg/plant (OF15), and 20 kg/plant (OF20). The relative indicators of enzyme activity of litchi rhizosphere soil, number of culturable microorganisms, microbial biomass, yield and quality under different treatments were compared.【Result】The results showed that compared with the CF treatment, when the chemical fertilizer application was reduced by 30%; Under the OF15 treatment, the invertase activity and urease activity of rhizosphere soil were increased by 35.3% and 25.6%, the number of actinomyces increased by 18.1%, and the microbial biomass nitrogen increased by 23.6%; Under the OF10 treatment, the phosphatase activity was increased by 32.2%, the number of fungi increased by 14.4%, the microbial biomass carbon increased by 26.1%; Under OF20 treatment, the number of culturable bacteria was increased by 11.8%. The application of organic fertilizer could significantly improve the quality and yield of litchi. Compared with the single application of chemical fertilizer, the yields under OF5, OF10, OF15 and OF20 treatments increased by 7.15%, 10.64%, 13.75% and 13.32%, respectively.【Conclusion】In conclusion, the application of 10kg-15kg pig manure organic fertilizer with chemical fertilizer reduced by 30% could significantly improve the quality and efficiency.

Abstract Oxaliplatin is a widely used chemotherapy drug for patients with advanced colorectal cancer (CRC); however, frequent drug resistance limits its therapeutic efficacy in patients. Here, this work identifies cyclin‐dependent kinase 1 (CDK1) as a critical contributor to oxaliplatin resistance via in vitro and in vivo CRISPR/Cas9 screening. CDK1 is highly expressed in oxaliplatin‐resistant cells and tissues due to the loss of N6‐methyladenosine modification. Genetic and pharmacological blockade of CDK1 restore the susceptibility of CRC cells to oxaliplatin in vitro and in cell/patient‐derived xenograft models. Mechanistically, CDK1 directly binds to and phosphorylates Acyl‐CoA synthetase long‐chain family 4 (ACSL4) at S447, followed by recruitment of E3 ubiquitin ligase UBR5 and polyubiquitination of ACSL4 at K388, K498, and K690, which leads to ACSL4 protein degradation. Reduced ACSL4 subsequently blocks the biosynthesis of polyunsaturated fatty acid containing lipids, thereby inhibiting lipid peroxidation and ferroptosis, a unique iron‐dependent form of oxidative cell death. Moreover, treatment with a ferroptosis inhibitor nullifies the enhancement of CRC cell sensitivity to oxaliplatin by CDK1 blockade in vitro and in vivo. Collectively, the findings indicate that CDK1 confers oxaliplatin resistance to cells by suppressing ferroptosis. Therefore, administration of a CDK1 inhibitor may be an attractive strategy to treat patients with oxaliplatin‐resistant CRC.

Abstract Background Lymphovascular invasion (LVI) and perineural invasion (PNI) can indicate poor survival outcomes in colorectal cancer, but few studies have focused on stage III colon cancer. The current study aimed to confirm the prognostic value of LVI and PNI and identify patients who could benefit from a complete duration of adjuvant chemotherapy based on the two pathological factors. Methods We enrolled 402 consecutive patients with stage III colon cancer who received colon tumor resection from November 2007 to June 2016 at Sun Yat-sen University Cancer Center. Survival analyses were performed by using Kaplan–Meier method with log-rank tests. Risk factors related to disease-free survival (DFS) and overall survival (OS) were identified through Cox proportional hazards analysis. Results 141 (35.1%) patients presented with LVI, and 108 (26.9%) patients with PNI. The LVI-positive group was associated with poorer 3-year DFS (86.5% vs. 76.3%, P = 0.001) and OS (96.0% vs. 89.1%, P = 0.003) rates compared with the LVI-negative group. The PNI-positive group showed a worse outcome compared with the PNI-negative group in 3-year DFS rate (72.5% vs. 86.7%, P

Active terahertz beam steering based on mechanical deformation of the LCE metasurface tuned infrared pump

Abstract To analyze the expression levels, prognostic value and immune infiltration association of Holliday junction protein (HJURP) as well as its feasibility as a pan-cancer biomarker for different cancers. The Protter online tool was utilized to obtain the localization of HJURP, then the methylation of HJURP in tumors were further explored. Thereafter, the mRNA data and clinical characteristics of 33 tumor types from TCGA database were obtained to investigate the expression and prognostic relationship of HJURP in different tumor types. Finally, the composition pattern and immune infiltration of HJURP in different tumors were detected in Tumor Immune Estimation Resource. HJURP was abnormally expressed in most of the cancer types and subtypes in TCGA database. Also, it was associated with poor prognosis of different cohorts. At the same time, the results also showed that HJURP was related to tumor immune evasion through different mechanisms, including T cell rejection and methylation in different cancer types. Besides, the methylation of HJURP was inversely proportional to mRNA expression levels, which mediated the dysfunctional phenotypes of T cells and poor prognosis of different cancer types. Alternatively, our results indicated that HJURP expression was associated with immune cell infiltration in a variety of cancers. HJURP may serve as an oncogenic molecule, and its expression and immune infiltration characteristics can be used as a biomarker for cancer detection, prognosis, treatment design and follow-up.

In view of the failure of rock anchors in spring thawing periods of seasonal freezing areas, this paper aims to investigate the anchorage ability of GFRP anchors under the action of freeze-thaw cycles.Through designing the physical model, loading tests were carried out on the test blocks experiencing 25, 50, and 75 freeze-thaw cycles.According to the test data and failure phenomena, the variation laws of the stress and bearing capacity of the GFRP bolt after freeze-thaw were analyzed.The results show that the freeze-thaw cycle will lead to a decrease in bonding performance between epoxy resin mortar and concrete. After 25, 50 and 75 cycles, the bearing capacity loss is 38.24%, 42.65% and 52.94%, respectively.The ultimate bearing capacity of the bolt decreases obviously with increasing freeze-thaw cycles. The freeze-thaw cycle accelerates the deterioration of the material properties of the bonding material and the surrounding rock. In the process, the load transfer to the interior is accelerated, leading to a reduction in the stress difference among points on the GFRP bolt, and the stress distribution of the bolt is more uniform than that at room temperature. Meanwhile, the deterioration of the material properties leads to local failure ahead of time, and the overall bearing capacity of the bolt is reduced.The research results can provide suggestions for the engineering application of GFRP anchor.

The recent era of fast optical manipulation and optical devices owe a lot to exciton-polaritons being lighter in mass, faster in speed and stronger in nonlinearity due to hybrid light-matter characteristics. The room temperature existence of polaritons in two dimensional materials opens up new avenues to the design and analysis of all optical devices and has gained the researchers attention. Here, spin-selective optical Stark effect is introduced to form a waveguide effect in uniform community of polaritons, and is used to realize polarization modulation of polaritons. The proposed device basically takes advantage of the spin-sensitive properties of optical Stark effect of polaritons inside the WS2 microcavity so as to guide different modes and modulate polarization of polaritons. It is shown that polaritonic wavepacket of different mode profiles can be generated by changing intensity of the optical Stark beam and the polarization of polaritons can be controlled and changed periodically along the formed waveguide by introduction birefringence that is sensitive to polarization degree of the optical Stark beam.

Abstract Background Compared with patients who require fewer antihypertensive agents, those with apparent treatment-resistant hypertension (aTRH) are at increased risk for cardiovascular and all-cause mortality, independent of blood pressure control. However, the etiopathogenesis of aTRH is still poorly elucidated. Methods We performed a genome-wide association study (GWAS) in first cohort including 586 aTRHs and 871 healthy controls. Next, expression quantitative trait locus (eQTL) analysis was used to identify genes that are regulated by single nucleotide polymorphisms (SNPs) derived from the GWAS. Then, we verified the genes obtained from the eQTL analysis in the validation cohort including 65 aTRHs, 96 hypertensives, and 100 healthy controls through gene expression profiling analysis and real-time quantitative polymerase chain reaction (RT-qPCR) assay. Results The GWAS in first cohort revealed four suggestive loci (1p35, 4q13.2-21.1, 5q22-23.2, and 15q11.1-q12) represented by 23 SNPs. The 23 significant SNPs were in or near LAPTM5, SDC3, UGT2A1, FTMT, and NIPA1. eQTL analysis uncovered 14 SNPs in 1p35 locus all had same regulation directions for SDC3 and LAPTM5. The disease susceptible alleles of SNPs in 1p35 locus were associated with lower gene expression for SDC3 and higher gene expression for LAPTM5. The disease susceptible alleles of SNPs in 4q13.2-21.1 were associated with higher gene expression for UGT2B4. GTEx database did not show any statistically significant eQTLs between the SNPs in 5q22-23.2 and 15q11.1-q12 loci and their influenced genes. Then, gene expression profiling analysis in the validation cohort confirmed lower expression of SDC3 in aTRH but no significant differences on LAPTM5 and UGT2B4, when compared with controls and hypertensives, respectively. RT-qPCR assay further verified the lower expression of SDC3 in aTRH. Conclusions Our study identified a novel association of SDC3 with aTRH, which contributes to the elucidation of its etiopathogenesis and provides a promising therapeutic target.

Abstract Background The number of colorectal cancer liver metastases (CRLMs) is usually considered a contradictory indicator to surgical resection. However, some patients with initially unresectable CRLMs can receive radical local treatment after conversion therapy. This study aimed to evaluate the effect of radical local treatment after conversion therapy and the prognosis of patients with more than 10 initially unresectable CRLMs. Methods Data for a total of 229 patients with initially unresectable CRLMs were retrospectively reviewed between December 2012 and January 2020. Among these patients, 107 had ≥10 CRLMs, and 122 had

Abstract Background The benefits and risks of intensive versus standard systolic blood pressure (SBP) treatment in older patients with arterial stiffness (AS) remains unclear. This study aims to investigate the interaction between the baseline AS and SBP treatments on cardiovascular outcomes. Methods In this post hoc analysis of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial, we involved 6865 participants with complete data regarding baseline brachial-ankle pulse wave velocity (baPWV). Patients were categorized by baseline AS status (AS, baPWV ≥ 1800 cm/s; non-AS, baPWV < 1800 cm/s). The primary outcome was a composite of cardiovascular events. The secondary outcomes were stroke, acute coronary syndrome (ACS), major cardiovascular events (MACE), and all-cause death. Cox regression was used to calculate hazard ratios for the outcomes. Results During a mean follow-up of 2.69 years, a total of 248 primary outcome events and 81 all-cause deaths occurred. The hazard ratios for the primary outcome were 0.76 (95% confidence interval (CI), 0.54–1.09) and 0.63 (95% CI, 0.43–0.92) in the AS and non-AS groups, respectively (P for interaction = 0.43), and that for stroke was 0.58 (95% CI, 0.33–1.02) and 0.48 (95% CI, 0.23–0.99) in the AS and non-AS groups, respectively (P for interaction = 0.68). Effects of intensive SBP treatment on safety outcomes and all-cause death were also similar in the two groups (P for interaction > 0.05 for all). Conclusions In the STEP trial, the beneficial effects of intensive SBP treatment were similar among those in the AS group and the non-AS group at baseline. Trial registration STEP ClinicalTrials.gov number, NCT03015311. Registered 2 January 2017.

Abstract The role of micro RNAs (miRNAs) in asthma remains unclear. In this study, we examined the role of miRNA in targeting FOXO1 in asthma. Results showed that miR-493-5p was one of the differentially expressed miRNAs in the PBMCs of asthmatic children, and was also associated with Th cell differentiation. The miR-493-5p expression decreased significantly in the OVA-induced asthma mice than the control groups. The miR-493-5p mimic inhibited the expression of the IL-9, IRF4 and FOXO1, while the inhibitor restored these effects. Moreover, the Dual-Luciferase analysis results showed FOXO1 as a novel valid target of miR-493-5p. According to the rescue experiment, miR-493-5p inhibited Th9 cell differentiation by targeting FOXO1. Then the exosomes in association with the pathogenesis of asthma was identified. Various inflammatory cells implicated in asthmatic processes including B and T lymphocytes, DCs, mast cells, and epithelial cells can release exosomes. Our results demonstrated that the DC-derived exosomes can inhibit Th9 cell differentiation through miR-493-5p, thus DC-derived exosomal miR-493-5p/FOXO1/Th9 may serve as a potential therapeutic target in the development of asthma.

Background: To investigate the genotype and clinical characteristics of carbapenem-resistant Enterobacteriaceae (CRE) strains in southwest China and provide information on the treatment stopping the spread of the infection. Methods: The clinical information of CRE isolates was collected from 19 hospitals in 12 cities across Sichuan Province, China, between June 2018 and April 2019. The isolates were detected by DNA sequencing of genes encoding carbapenem enzymes and multilocus sequence types (MLSTs). Results: A total of 166 nonrepetitive CRE isolates were isolated during the study period from sputum, blood, urine, and other samples. Klebsiella pneumoniae carbapenemase (KPC) was dominant in Klebsiella pneumoniae (53.9%), followed by New Delhi metallo-β-lactamase (NDM) (42.1%). A total of 43 STs were detected. The most common ST of K. pneumoniae was ST11, and that of Escherichia coli was ST410. Pairwise single nucleotide polymorphism (SNP) distances and the likelihood of local transmission by epidemiology were plotted for each species. About 65% of these pairs had ≤ 20 pairwise SNPs. Conclusion: A large number of CRE strains carried carbapenemase. Although NDM-ST12 K. pneumoniae should not be disregarded, KPC-ST11is the predominant strain. Thus, the possibility of transmission between E. coli and K. pneumoniae could not be ignored.

IntroductionIn urban road scenes, due to the small size of traffic signs and the large amount of surrounding interference information, current methods are difficult to achieve good detection results in the field of unmanned driving.MethodsTo address the aforementioned challenges, this paper proposes an improved E-YOLOv4-tiny based on the YOLOv4-tiny. Firstly, this article constructs an efficient layer aggregation lightweight block with deep separable convolutions to enhance the feature extraction ability of the backbone. Secondly, this paper presents a feature fusion refinement module aimed at fully integrating multi-scale features. Moreover, this module incorporates our proposed efficient coordinate attention for refining interference information during feature transfer. Finally, this article proposes an improved S-RFB to add contextual feature information to the network, further enhancing the accuracy of traffic sign detection.Results and discussionThe method in this paper is tested on the CCTSDB dataset and the Tsinghua-Tencent 100K dataset. The experimental results show that the proposed method outperforms the original YOLOv4-tiny in traffic sign detection with 3.76% and 7.37% improvement in mAP, respectively, and 21% reduction in the number of parameters. Compared with other advanced methods, the method proposed in this paper achieves a better balance between accuracy, real-time performance, and the number of model parameters, which has better application value.

Artificially designed modulators that enable a wealth of freedom in manipulating the terahertz (THz) waves at will are an essential component in THz sources and their widespread applications. Dynamically controlled metasurfaces, being multifunctional, ultrafast, integrable, broadband, high contrasting, and scalable on the operating wavelength, are critical in developing state-of-the-art THz modulators. Recently, external stimuli-triggered THz metasurfaces integrated with functional media have been extensively explored. The vanadium dioxide (VO2)-based hybrid metasurfaces, as a unique path toward active meta-devices, feature an insulator–metal phase transition under the excitation of heat, electricity, and light, etc. During the phase transition, the optical and electrical properties of the VO2 film undergo a massive modification with either a boosted or dropped conductivity by more than four orders of magnitude. Being benefited from the phase transition effect, the electromagnetic response of the VO2-based metasufaces can be actively controlled by applying external excitation. In this review, we present recent advances in dynamically controlled THz metasurfaces exploiting the VO2 phase transition categorized according to the external stimuli. THz time-domain spectroscopy is introduced as an indispensable platform in the studies of functional VO2 films. In each type of external excitation, four design strategies are employed to realize external stimuli-triggered VO2-based THz metasurfaces, including switching the transreflective operation mode, controlling the dielectric environment of metallic microstructures, tailoring the equivalent resonant microstructures, and modifying the electromagnetic properties of the VO2 unit cells. The microstructures’ design and electromagnetic responses of the resulting active metasurfaces have been systematically demonstrated, with a particular focus on the critical role of the VO2 films in the dynamic modulation processes.

Abstract Background Acute myeloid leukemia (AML) is a group of highly heterogenous and aggressive blood cancer. Despite recent progress in its diagnosis and treatment, patient outcome is variable and drug resistance results in increased mortality. The siglec family plays an important role in tumorigenesis and aging. Increasing age is a risk factor for AML and cellular aging contributes to leukemogenesis via various pathways. Methods The differential expression of the siglec family was compared between 151 AML patients and 70 healthy controls, with their information downloaded from TCGA and GTEx databases, respectively. How siglec expression correlated to AML patient clinical features, immune cell infiltration, drug resistance and survival outcome was analyzed. Differentially expressed genes in AML patients with low- and high-expressed siglec9 and siglec14 were analyzed and functionally enriched. The aging-related gene set was merged with the differentially expressed genes in AML patients with low and high expression of siglec9, and merged genes were subjected to lasso regression analysis to construct a novel siglec-based and aging-related prognostic model. The prediction model was validated using a validation cohort from GEO database (GSE106291). Results The expression levels of all siglec members were significantly altered in AML. The expression of siglecs was significantly correlated with AML patient clinical features, immune cell infiltration, drug resistance, and survival outcome. Based on the differentially expressed genes and aging-related gene set, we developed a 9-gene prognostic model and decision curve analysis revealed the net benefit generated by our prediction model. The siglec-based and aging-related 9-gene prognostic model was tested using a validation data set, in which AML patients with higher risk scores had significantly reduced survival probability. Time-dependent receiver operating characteristic curve and nomogram were plotted and showed the diagnostic accuracy and predictive value of our 9-gene prognostic model, respectively. Conclusions Overall, our study indicates the important role of siglec family in AML and the good performance of our novel siglec-based and aging-related 9-gene signature in predicting AML patient outcome.

Objective: Klebsiella pneumoniae carbapenemase (KPC)-producing K.pneumoniae has represented a serious health problem in worldwide. The resistance to ceftazidime-avibactam (CAZ-AVI) began to emerge since its approval in 2015. We aim to explore the resistance mechanism of CAZ-AVI. Methods: Phenotypic test and whole-genome sequencing (WGS) analysis were performed in KP-HX0917 and KP-HX1016 Klebsiella pneumoniae isolates, collected from the same patient following treatment with CAZ-AVI. Results: We report a case of emergence of CAZ-AVI resistance in ST 11 KPC-2-producing K. pneumoniae (KP-HX1016) during 14 days of exposure with CZA-AVI. Molecular analysis highlighted the A533C mutation in the blaKPC-2 gene, resulting a D179A substitution in protein sequence, which restored the hydrolysis ability of imipenem and meropenem, but not for ertapenem, and the result of phenotypic test was negative. However, KP-HX0917 produced serine-carbapenemase by phenotypic detection and lost its capacity of hydrolyzing carbapenems. Conclusion: The emergence of CAZ-AVI resistance should arouse our attention, the susceptibility testing should be followed by a combination of phenotypic and molecular methods, to make sure that no potential carbapenemase-producing bacteria are missed.

Prostate cancer (PCa) is the most common malignant tumor in men. Prostate-specific membrane antigen (PSMA), which is overexpressed on the surface of Prostate cancer cells, may serve as a potential therapeutic target. Recently, image-guided and targeted therapy for prostate cancers has attracted much attention by using Prostate-specific membrane antigen targeting nanoparticle. In this study, we produced PSMA-targeted light-responsive nanosystems. These nanosystems of liquid perfluorocarbon cores and polymer shells were loaded with the photosensitizer IR780 and therapeutic drugs paclitaxel. The liquid perfluorocarbon (PFP) in nanoparticles can perform ultrasound-enhanced imaging by liquid-gas transition and promote the deliver and release of paclitaxel. IR780 can perform photothermal therapy (PTT) guided by photoacoustic (PA) imaging. Combination treatment with photothermal therapy and chemotherapy exhibited excellent inhibition of cell proliferation in vitro and a significant therapeutic effect in vivo. In conclusion, we successfully formulated PSMA-targeted nanosystems with precision targeting and ultrasound/PA dual-modality imaging for anti-tumor effects.

Background: The genetic factors in assessing therapeutic efficacy and predicting antihypertensive drug response are unclear. Therefore, this study aims to identify the associations between variants and antihypertensive drug response.Methods: A longitudinal study including 1837 hypertensive patients was conducted in Northern China and followed up for a median 2.24 years. The associations of 11 candidate variants with blood pressure changes in response to antihypertensive drugs and with the risk of cardiovascular events during the follow-up were examined. The dual-luciferase assay was carried out to assess the effect of genetic variants on gene transcriptional activity.Results: The variant rs11039149A>G in the promoter of nuclear receptor subfamily 1 group H member 3 (NR1H3) was associated with the change in systolic blood pressure (ΔSBP) in response to calcium channel blockers (CCBs) monotherapy. Patients carrying rs11039149AG genotype showed a significant increase of systolic blood pressure (SBP) at follow-up compared with AA carriers, and the difference of ΔSBP between AG and AA carriers was 5.94 mm Hg (95%CI: 2.09–9.78, p = 0.002). In 1,184 patients with CCBs therapy, SBP levels decreased in AA carriers, but increased in AG carriers, the difference of ΔSBP between AG and AA carriers was 8.04 mm Hg (95%CI: 3.28–12.81, p = 0.001). Further analysis in 359 patients with CCBs monotherapy, the difference of ΔSBP between AG and AA carriers was 15.25 mm Hg (95%CI: 6.48–24.02, p = 0.001). However, there was no significant difference in ΔSBP between AG and AA carriers with CCBs multitherapy. The rs11039149A>G was not associated with the cardiovascular events incidence during the follow-up. Additionally, transcriptional factor forkhead box C1 (FOXC1) bound to the NR1H3 promoter containing rs11039149A and significantly increased the transcriptional activity, while rs11039149 A to G change led to a loss-of-function and disabled FOXC1 binding. For the other 10 variants, associations with blood pressure changes or risk of cardiovascular events were not observed.Conclusion: Hypertensive patients with rs11039149AG genotype in the NR1H3 gene have a significant worse SBP control in response to CCBs monotherapy compared with AA carriers. Our findings suggest that the NR1H3 gene might act as a promising genetic factor to affect individual sensitivity to antihypertensive drugs.

Developing an electrolyte that is compatible with both high-voltage cathodes and Li metal anodes has always been challenging. Here, the authors created a new strategy by engineering a passivating electric double layer to achieve a fast-charging and lowtemperature high voltage lithium metal batteries.

Cobalt blue ceramic pigments mainly consisting of CoAl2O4 are subject to the difficulty of color control. Here, a perspective is reported regarding research on the reasons for color change based on the control of the heat treatment and ratio of components. Macroscopically, the composition of pigment powders determines the color. Microscopically, the crystallite characters including size, cation distribution, and structure have an important effect on the color. The ingredient, structural, and color properties of the pigment powders are analyzed using thermo gravimetry–differential scanning calorimetry (TG–DSC), X-ray diffraction (XRD) measurement, Rietveld refinement, energy dispersive spectrometer (EDS), and colorimetry analysis. The color is proven to be associated with cation distribution, such as that of Co2+ and Co3+. It is indicated that high heating temperature, long heating time, and a large proportion of Al3+ can, respectively, induce the Co2+ and Al3+ in tetrahedral and octahedral sites.

The utilization of Co-Cr-Fe-based black pigments bears considerable significance within the realm of commercial ceramic pigments, owing to their distinctive spinel structure, remarkable high-temperature stability, and exceptional chromatic attributes. This study delves into the synthesis of diverse black pigment configurations by employing the co-precipitation method, leveraging the interplay of these three metallic oxides. This investigation encompasses a comprehensive scrutiny of ion valences, crystal structures and parameters, colorimetric properties, and their interrelationships. The methodology integrates the response surface methodology (RSM) framework, using theoretical formulations to navigate the material ratios and elucidating the associations between the resultant compositions and color coordinate values, aligned with the CIE-Lab* colorimetric methodology. The derived predictive models yielded an optimized black pigment composition, characterized by heightened black intensity and a refined formulation.

Topological photonic devices provide a powerful platform to control the flow of light because their topologically protected edge states can be immune to backscattering and be robust to impurities, disorders, and defects. As one of the topological photonic systems, valley photonic crystals have attracted great attention because they can achieve a large bandgap and be easily combined with modern micro-nano fabrication technology. Terahertz photonic devices are of enormous interest in next-generation communications. Here, we design a valley photonic crystal consisting of a triangular lattice with three metal rod scatterers. By rotating the three metal rods in opposite directions to break the inversion symmetry, we achieve a bandgap width of up to 70% and observe the transport of the edge states in the terahertz region. By replacing part of the structure with phase change material VO2, on/off switching of the terahertz photonic topological edge states is realized, and the attenuation can be also modeled by adjusting the size of the VO2 region. The proposed regime has potential applications in sensing and 6G communications.