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Abstract METTL14 functions as an RNA methyltransferase involved in m6A modification, influencing mRNA biogenesis, decay, and translation processes. However, the specific mechanism by which METTL14 regulates glucose-6-phosphate dehydrogenase (G6PD) to promote the progression of lung adenocarcinoma (LUAD) is not well understood. Quantitative measurement and immunohistochemistry (IHC) analysis have demonstrated higher levels of m6A in LUAD tissues compared to adjacent normal tissues. Additionally, the expression of METTL14 was significantly increased in LUAD tissues. In LUAD cell lines, both METTL14 and m6A levels were elevated compared to normal human lung epithelial cells. Knockdown of METTL14 markedly reduced LUAD cell proliferation, migration, and invasion. Conversely, overexpression of METTL14, but not the mutant form, significantly enhanced these cellular processes in LUAD. In vivo studies using nude mice with subcutaneously transplanted LUAD cells demonstrated that stable METTL14 knockdown led to notably reduced tumor volume and weight, along with fewer Ki67-positive cells and lung metastatic sites. Importantly, METTL14 knockdown reduced glycolytic activity in LUAD cells. Through a combination of RNA sequencing and MeRIP-sequencing, we identified numerous altered genes and confirmed that IGF2BP2 enhances G6PD mRNA stability after METTL14-mediated m6A modification, thereby promoting tumor growth and metastasis. Moreover, LUAD patients with higher levels of G6PD had poorer overall survival (OS). In conclusion, our study indicates that METTL14 upregulates G6PD expression post-transcriptionally through an m6A-IGF2BP2-dependent mechanism, thereby stabilizing G6PD mRNA. These findings propose potential diagnostic biomarkers and effective targets for anti-metabolism therapy in LUAD.

Pedestrian safety evacuation in aircraft cabins has been a challenging problem because of the aircraft's unique characteristics, such as the diversity of passengers and the restricted evacuation environment. It is difficult to reproduce evacuation activities in aircraft cabin due to safety concerns and cost constraints. To fill this gap, an improved cellular automaton model of crowd evacuation for aircraft cabin is established by incorporating the characteristics of cabin space structures and passenger attributes. Passengers are divided into healthy individual passengers and disabled-healthy group passengers, whose movement mechanisms are quantified. Based on the constructed model, simulation experiments are conducted using the configuration cabin layout of B737-800 as an example. The results show that the evacuation time is prolonged with increased passenger density and the number of disabled passengers. Moreover, the overall evacuation time is insignificantly affected by whether disabled-healthy group passengers' seats are close to the aisle or window, and the evacuation efficiency is best when their seats are evenly distributed in the cabin. The evacuation time is the shortest when all cabin doors are open, and pedestrians are evacuated the slowest when the central emergency doors are closed. This study provides valuable insights into effective strategies for pedestrian evacuation and crowd emergency management of civil aircraft.

Developing eco-friendly, degradable, and flexible electronic devices using renewable cellulose, such as waste agricultural straw, is increasingly vital. This approach tackles the growing issue of nondegradable electronic waste. In this study, flexible transparent electrodes (FTEs) were created using cellulose from waste corn straw, embedding silver nanowires (AgNWs) networks within the surface layer. This method is suitable for reel-to-reel processing. These sustainable FTEs had high transparency and conductivity, with a film resistance of 45.4 Ω/sq and light transmittance of 86.2% at 550 nm. The "dissolution–regeneration" self-assembly process harnesses cellulose's hydrogen bond network to stabilize the AgNWs network, providing the FTEs with excellent electromechanical stability. Resistance changes were less than 3% during bending, folding, and 1,000-time cyclic bending tests. Furthermore, these electrodes showed remarkable environmental stability, with only a 2.5% resistance increase after 16 days at room temperature. This research demonstrates a new application for agricultural straw cellulose in flexible electronics, offering a sustainable alternative in electronic materials.

Significance Cobalt is an important strategic mineral resource and plays an irreplaceable role in aerospace, battery and other industries. Cobalt is mainly concentrated in few countries around the world and is one of the scarcest mineral resources in China. The cobalt ore resources in China are heavily dependent on imports. Therefore, research on cobalt ore resources is vital to reduce the bottleneck risk and to sustain the economic development. Progress This paper systematically reviewed geochemical properties and mineral types of cobalt and the genetic types, formation mechanisms, and spatiotemporal distribution of cobalt deposits in the world and China. Conclusions and prospects The existing problems of cobalt deposits are comprehensively summarized in the study and future research should be focused on the ore-forming age and the dynamic background of cobalt deposits, the source, migration and enrichment mechanism, and the occurrence of cobalt. This study aims to provide a new reference for the study of cobalt deposits and the exploration and development of cobalt resources in China.

Purpose: Kawasaki disease(KD) is a vascular inflammatory disease that was first identified in 1967. Numerous studies have been conducted on KD and have yielded valuable recent insights. This current bibliometric analysis aimed to determine the intellectual landscape of research interest in KD. Methods: Publications were collected from the Web of Science Core Collection. Bibliometric tools such as CiteSpace and VOSviewer were utilized to analyze the research focus, emerging trends, frontiers, and hot topics in this specific field. Results: A total of 6122 articles on KD were retrieved. Pediatric Cardiology, Pediatrics International, and Pediatric Infections Disease Journal were the three most productive journals reporting KD development. The University of California San Diego was the most productive institution, with 230 publications. The USA was the most productive country, with 1661 articles in KD. SARS-CoV-2, diagnostic serum biomarkers, and risk factor prediction models for coronary arterial lesions and subtypes of KD are popular topics in KD research. Factors that induce smooth muscle cell transition to myofibroblastic cell, potentially halting the subacute/chronic vasculitis process and endothelial dysfunction in macrophage activation syndrome associated with KD were the frontiers in the study of KD. Conclusion: KD has attracted widespread attention worldwide that has continued to increase since 1974. The most productive institution and country are the University of California San Diego and the USA, respectively. SARS-CoV-2, serum biomarkers, and prediction models are hot topics in this field.

Background: Necroptosis could regulate immunity in cancers, and stratification of colorectal cancer (CRC) subtypes based on key genes related to necroptosis might be a novel strategy for CRC treatment. Method: The RNA-sequencing data of CRC and other 31 types of cancers were obtained from The Cancer Genome Atlas (TCGA) database. Consensus clustering was performed based on protein-coding genes (PCGs) related to necroptosis score calculated by single sample gene set enrichment analysis (ssGSEA). Module genes showing a significant positive correlation with the necroptosis score were identified by weighted correlation network analysis (WGCNA) and further used to develop a risk stratification model applying least absolute shrinkage and selection operator (LASSO) and Cox regression analysis. The risks score for each sample in CRC cohorts, immunotherapy cohorts and pan-cancer study cohorts was calculated. Result: Two subgroups (C1 cluster and C2 cluster) of CRC were identified based on the necroptosis score. Compared with C1 cluster, the survival possibility of C2 cluster was greatly reduced, the levels of necroptosis score, immune cell infiltration, immune score and expression of immune checkpoint molecules were significantly increased and immunotherapy response was less active. Low-risk patients defined by the risk model had a significant survival advantage than high-risk counterparts in both CRC and the other 31 cancer types. Furthermore, the risk model was also more efficient than the Tumor Immune Dysfunction and Exclusion (TIDE) tool in predicting OS and immunotherapy response for the samples in the immunotherapy cohort. Conclusion: CRC patients were classified by necroptosis score-related PCGs, and a risk model was designed to evaluate the immunotherapy and prognosis of patients with CRC. The current molecular subtype and prognostic model could help stratify patients with different risks and predict their prognosis and immunotherapy sensitivity.

Background Stomach adenocarcinoma (STAD) exhibits profound tumor heterogeneity and represents a great therapeutic challenge. Single-cell sequencing technology is a powerful tool to identify characteristic cell types. Methods Single-cell sequencing data (scRNA-seq) GSE167297 and bulk RNA-seq data from TCGA, GTEx, GSE26901 and GSE15459 database were included in this study. By downscaling and annotating the cellular data in scRNA-seq, critical cell types in tumor progression were identified by AUCell score. Relevant gene modules were then identified by weighted gene co-expression network analysis (WGCNA). A prognostic scoring system was constructed by identifying prognostic factors in STAD by Least absolute shrinkage and selection operator (LASSO) COX model. The prognosis and model performance in the RiskScore groups were measured by Kaplan-Meier (K-M) curves and Receiver operating characteristic (ROC) curves. Nomogram was drawn based on RiskScore and prognosis-related clinical factors. In addition, we evaluated patient’s feedback on immunotherapy in the RiskScore groups by TIMER, ESTIMATE and TIDE analysis. Finally, the expression levels of prognostic factors were verified in gastric cancer cell lines (MKN7 and MKN28) and human normal gastric mucosal epithelial cells (GES-1), and the effects of prognostic factors on the viability of gastric cancer cells were examined by the CCK8 assay and cell cycle. Results scRNA-seq analysis revealed that 11 cell types were identified, and macrophages exhibited relatively higher AUCell scores and specifically expressed CD14 and FCGR3A. High macrophage scores worsened the prognosis of STAD patients. We intersected the specifically expressed genes in macrophages subgroups (670) and macrophage module genes (2,360) obtained from WGCNA analysis. Among 86 common genes, seven prognostic factors (RGS2, GNAI2, ANXA5, MARCKS, CD36, NRP1 and PDE4A) were identified and composed a RiskScore model. Patients in low Risk group showed a better survival advantage. Nomogram also provided a favorable prediction for survival at 1, 3 and 5 years in STAD patients. Besides, we found positive feedback to immunotherapy in patients with low RiskScore. The expression tendency of the seven prognostic factors in MKN7 and MKN28 was consistent with that in the RNA-seq data in addition to comparison of protein expression levels in the public HPA (The Human Protein Atlas) database. Further functional exploration disclosed that MARCKS was an important prognostic factor in regulating cell viability in STAD. Conclusion This study preliminary uncovered a single cell atlas for STAD patients, and Macrophages relevant gene signature and nomogram displayed favorable immunotherapy and prognostic prediction ability. Collectively, our work provides a new insight into the molecular mechanisms and therapeutic approach for LUAD patients.

Untreated or inadequately treated silver−containing wastewater may pose adverse effects on hu−man health and the ecological environment. Currently, significant progress has been made in the treatment of Ag(I) in wastewater using adsorption methods, with adsorbents playing a pivotal role in this process. This paper provides a systematic review of various adsorbents for the recovery and treatment of Ag(I) in wastewater, including MOFs, COFs, transition metal sulfides, metal oxides, biomass materials, and other polymeric materials. The adsorption mechanisms of these materials for Ag(I) are elaborated upon, along with the challenges currently faced. Furthermore, insights into optimizing adsorbents and developing novel adsorbents are proposed in this study.

Targeting the tumor microenvironment is increasingly recognized as an effective treatment of advanced lung adenocarcinoma (LUAD). However, few studies have addressed the efficacy of immunotherapy for LUAD. Here, a novel method for predicting immunotherapy efficacy has been proposed, which combines single-cell and bulk sequencing to characterize the immune microenvironment and metabolic profile of LUAD. TCGA bulk dataset was used to cluster two immune subtypes: C1 with “cold” tumor characteristics and C2 with “hot” tumor characteristics, with different prognosis. The Scissor algorithm, which is based on these two immune subtypes, identified GSE131907 single cell dataset into two groups of epithelial cells, labeled as Scissor_C1 and Scissor_C2. The enrichment revealed that Scissor_C1 was characterized by hypoxia, and a hypoxic microenvironment is a potential inducing factor for tumor invasion, metastasis, and immune therapy non-response. Furthermore, single cell analysis was performed to investigate the molecular mechanism of hypoxic microenvironment-induced invasion, metastasis, and immune therapy non-response in LUAD. Notably, Scissor_C1 cells significantly interacted with T cells and cancer-associated fibroblasts (CAF), and exhibited epithelial–mesenchymal transition and immunosuppressive features. CellChat analysis revealed that a hypoxic microenvironment in Scissor_C1elevated TGFβ signaling and induced ANGPTL4 and SEMA3C secretion. Interaction with endothelial cells with ANGPTL4, which increases vascular permeability and achieves distant metastasis across the vascular endothelium. Additionally, interaction of tumor-associated macrophages (TAM) and Scissor_C1 via the EREG/EFGR pathway induces tyrosine kinase inhibitor drug-resistance in patients with LAUD. Thereafter, a subgroup of CAF cells that exhibited same features as those of Scissor_C1 that exert immunosuppressive functions in the tumor microenvironment were identified. Moreover, the key genes (EPHB2 and COL1A1) in the Scissor_C1 gene network were explored and their expressions were verified using immunohistochemistry. Finally, the metabolism dysfunction in cells crosstalk was determined, which is characterized by glutamine secretion by TAM and uptake by Scissor_C1 via SLC38A2 transporter, which may induce glutamine addiction in LUAD cells. Overall, single-cell sequencing clarifies how the tumor microenvironment affects immunotherapy efficacy via molecular mechanisms and biological processes, whereas bulk sequencing explains immunotherapy efficacy based on clinical information.

In this study, coal fly ash was functionalized, using a simple one-step process (loading with Al3+ and sulfonation), to yield a solid acid catalyst (S/Al-CFA) with strong acid sites. The catalyst was then used to produce furfural from xylose in a biphasic system (H2O(NaCl)/tetrahydrofuran). The furfural yield reached 82% at 180 °C–60 min with catalyst/xylose ratio of 0.2:1.0 (w/w). With the reaction completed, all of the components could be effectively separated, and the furfural was 97.6% pure. The cycle and regeneration of the catalyst were evaluated, and the catalyst deactivation mechanism was investigated.

The increasing incidence of aircraft cargo compartment fires in recent years has caused heavy losses and drawn attention to understanding the combustion process, especially under low pressure. The present paper aims at exploring the conditions of flashover at different pressures. Experiments were conducted in Guanghan (96 kPa) and Kangding (60 kPa), which are located at different altitudes. Five different sizes of pool fires were tested and smoke temperature and heat flux were measured for flashover criteria analysis. Corresponding simulations were performed using a commercial software FDS to examine the pressure effect on the flashover phenomenon and to validate the simulation results. The critical conditions for the onset of flashover in a 1/4 MPS compartment were found to be (1) an average upper layer temperature of about 450 °C at 96 kPa or about 550 °C at 60 kPa, and (2) radiant heat flux at floor level of about 10 to 15 kW/m2 at 96 kPa or 20 to 25 kW/m2 at 60 kPa. By using the average upper layer temperature as a criterion in modeling, a relatively accurate prediction of flashover onset time could be obtained at 96 kPa and a delay of about 25 s was found at 60 kPa.

Kawasaki disease (KD) is an acute, self-limited vasculitis, and the etiology is still unclear. Coronary arterial lesions (CALs) are a major complication of KD. Excessive inflammation and immunologic abnormities are involved in the pathogenesis of KD and CALs. Annexin A3 (ANXA3) plays crucial roles in cell migration and differentiation, inflammation, cardiovascular and membrane metabolic diseases. The purpose of this study was to investigate the effect of ANXA3 on the pathogenesis of KD and CALs. There were 109 children with KD in the KD group [which was divided into two groups: 67 patients with CALs in the KD-CAL group, and 42 patients with noncoronary arterial lesions (NCALs) in the KD-NCAL group] and 58 healthy children in the control (HC) group. Clinical and laboratory data were retrospectively collected from all patients with KD. The serum concentration of ANXA3 was measured by enzyme-linked immunosorbent assays (ELISAs). Serum ANXA3 levels were higher in the KD group than in the HC group (P

Background: Drug resistance and recurrence often develop during the treatment of muscle-invasive bladder cancer (MIBC). The existence of cancer stem cells (CSCs) in MIBC makes the formulation of effective treatment strategies extremely challenging. We aimed to use single-cell RNA sequencing approaches to identify CSCs and evaluate their molecular characteristics and to discover possible therapeutic measures.Methods: GEO data sets GSE130001 and GSE146137 were used to construct an expression matrix. After cells were identified by type, malignant epithelial cells inferred by InferCNV were extracted for stemness evaluation. The subset of cells with the highest stemness was subjected to weighted gene coexpression network analysis (WGCNA) and pseudotime analysis to identify key genes. In addition, we predicted drug sensitivity relationships for key genes in CTD and predicted the correlation between drugs and survival through siGDC.Results: We found that there were some CSCs in MIBC samples. The CSC population was heterogeneous during tumor development and was divided into quiescent and proliferating CSCs. We identified DBI as the key gene in quiescent CSCs. Analysis of a TCGA data set showed that higher DBI expression indicated higher histological grade. In addition, we predicted that acetaminophen can reduce DBI expression, thereby reducing the stemness of CSCs. Thus, we identified a potential new use of acetaminophen.Conclusion: We systematically explored CSCs in tumors and determined that DBI may be a key gene and potential therapeutic target in quiescent CSCs. In addition, we confirmed that acetaminophen may be a candidate drug targeting CSCs, improving our understanding of CSC-targeting therapeutic strategies.

In recent years, many studies have indicated that vitamin C might be negatively associated with the risk of cancer, but the actual relationship between vitamin C and cancer remains ambivalent. Therefore, we utilized a two-sample Mendelian randomization (MR) study to explore the causal associations of genetically predicted vitamin C with the risk of a variety of cancers. Single-nucleotide polymorphisms (SNPs) associated with vitamin C at a significance level of p < 5 × 10–8 and with a low level of linkage disequilibrium (LD) (r2 < 0.01) were selected from a genome-wide association study (GWAS) meta-analysis of plasmid concentration of vitamin C consisting of 52,018 individuals. The data of the GWAS outcomes were obtained from United Kingdom Biobank, FinnGen Biobank and the datasets of corresponding consortia. In the inverse-variance weight (IVW) method, our results did not support the causal association of genetically predicted vitamin C with the risk of overall cancer and 14 specific types of cancer. Similar results were observed in sensitivity analyses where the weighted median and MR-Egger methods were adopted, and heterogeneity and pleiotropy were not observed in statistical models. Therefore, our study suggested that vitamin C was not causally associated with the risk of cancer. Further studies are warranted to discover the potential protective and therapeutic effects of vitamin C on cancer, and its underlying mechanisms.

Epithelial-mesenchymal transition (EMT) and ferroptosis are two important processes in biology. In tumor cells, they are intimately linked. We used single-cell RNA sequencing to investigate the regulatory connection between EMT and ferroptosis tendency in LUAD epithelial cells. We used Seurat to construct the expression matrix using the GEO dataset GSE131907 and extract epithelial cells. We found a positive correlation between the trends of EMT and ferroptosis tendency. Then we used SCENIC to analyze differentially activated transcription factors and constructed a molecular regulatory directed network by causal inference. Some ferroptosis markers (GPX4, SCP2, CAV1) were found to have strong regulatory effects on EMT. Cell communication networks were constructed by iTALK and implied that Ferro_High_EMT_High cells have a higher expression of SDC1, SDC4, and activation of LGALS9-HARVCR2 pathways. By deconvolution of bulk sequencing, the results of CIBERSORTx showed that the co-occurrence of ferroptosis tendency and EMT may lead to tumor metastasis and non-response to immunotherapy. Our findings showed there is a strong correlation between ferroptosis tendency and EMT. Ferroptosis may have a promotive effect on EMT. High propensities of ferroptosis and EMT may lead to poor prognosis and non-response to immunotherapy.

Developing influenza vaccines that protect against a broad range of viruses is a global health priority. Several conserved viral proteins or domains have been identified as promising targets for such vaccine development. However, none of the targets is sufficiently immunogenic to elicit complete protection, and vaccine platforms that can enhance immunogenicity and deliver multiple antigens are desperately needed. Here, we report proof-of-concept studies for the development of next-generation influenza vaccines using the bacteriophage T4 virus-like particle (VLP) platform. Using the extracellular domain of influenza matrix protein 2 (M2e) as a readout, we demonstrate that up to ~1,281 M2e molecules can be assembled on a 120 x 86 nanometer phage capsid to generate M2e-T4 VLPs. These M2e-decorated nanoparticles, without any adjuvant, are highly immunogenic, stimulate robust humoral as well as cellular immune responses, and conferred complete protection against lethal influenza virus challenge. Potentially, additional conserved antigens could be incorporated into the M2e-T4 VLPs and mass-produced in E. coli in a short amount of time to deal with an emerging influenza pandemic.

As smart devices and mobile positioning technologies improve, location-based services (LBS) have grown in popularity. The LBS environment provides considerable convenience to users, but it also poses a significant threat to their privacy. A large number of research works have emerged to protect users’ privacy. Dummy-based location privacy protection solutions have been widely adopted for their simplicity and enhanced privacy protection results, but there are few reviews on dummy-based location privacy protection. Or, for existing works, some focus on aspects of cryptography, anonymity, or other comprehensive reviews that do not provide enough reviews on dummy-based privacy protection. In this paper, the authors provide a review of dummy-based location privacy protection techniques for location-based services. More specifically, the connection between the level of privacy protection, the quality of service, and the system overhead is summarized. The difference and connection between various location privacy protection techniques are also described. The dummy-based attack models are presented. Then, the algorithms for dummy location selection are analyzed and evaluated. Finally, we thoroughly evaluate different dummy location selection methods and arrive at a highly useful evaluation result. This result is valuable both to users and researchers who are studying this field.

Recent research suggests that melatonin (Mel), an endogenous hormone and natural supplement, possesses anti-proliferative effects and can sensitise cells to anti-cancer therapies. Although shikonin (SHK) also possesses potential anti-cancer properties, the poor solubility and severe systemic toxicity of this compound hinders its clinical usage. In this study, we combined Mel and SHK, a potentially promising chemotherapeutic drug combination, with the aim of reducing the toxicity of SHK and enhancing the overall anti-cancer effects. We demonstrate for the first time that Mel potentiates the cytotoxic effects of SHK on cancer cells by inducing oxidative stress via inhibition of the SIRT3/SOD2-AKT pathway. Particularly, Mel-SHK treatment induced oxidative stress, increased mitochondrial calcium accumulation and reduced the mitochondrial membrane potential in various cancer cells, leading to apoptosis. This drug combination also promoted endoplasmic reticulum (ER) stress, leading to AKT dephosphorylation. In HeLa cells, Mel-SHK treatment reduced SIRT3/SOD2 expression and SOD2 activity, while SIRT3 overexpression dramatically reduced Mel-SHK-induced oxidative stress, ER stress, mitochondrial dysfunction and apoptosis. Hence, we propose the combination of Mel and SHK as a novel candidate chemotherapeutic regimen that targets the SIRT3/SOD2-AKT pathway in cancer.

Abstract Hydrogen sulfide (H2S) is involved in cancer biological processes. However, there are several controversies concerning the role of H2S in cancer development and progression. In this study, we found that the growth and migration of hepatocellular carcinoma (HCC) cells were enhanced by 10–100 μM NaHS and dose-dependently inhibited by 600–1000 μM NaHS. The apoptotic levels were reduced by 25–100 μM NaHS but increased by 400–1000 μM NaHS in HCC cells. After treatment with 25–50 μM NaHS, the protein levels of p-EGFR, p-ERK, MMP-2, and p-AKT were increased, whereas the levels of PTEN and the ratio of BAX/BCL-2 were down-regulated. Administration of 800–1000 μM NaHS showed opposite effects on these protein levels in HCC cells. However, H2S showed no effects on the growth, migration, apoptosis, and the protein levels of the EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways in L02 cells. Furthermore, 25–100 μM NaHS promoted HCC tumor growth and blood vessel formation, while 800–1000 μM NaHS inhibited angiogenesis and tumor growth with no obvious systemic toxicity. These results indicate that H2S acts as a double-edged sword in HCC cells through EGFR/ERK/MMP-2 and PTEN/AKT signaling pathways. Novel H2S donors could be designed and applied for further antitumor research.

The generation of chrysanthemum (Chrysanthemum × morifolium) flower color is mainly attributed to the accumulation of anthocyanins. In the anthocyanin biosynthetic pathway in chrysanthemum, although all of the structural genes have been cloned, the regulatory function of R2R3-MYB transcription factor (TF) genes, which play a crucial role in determining anthocyanin accumulation in many ornamental crops, still remains unclear. In our previous study, four light-induced R2R3-MYB TF genes in chrysanthemum were identified using transcriptomic sequencing. In the present study, we further investigated the regulatory functions of these genes via phylogenetic and alignment analyses of amino acid sequences, which were subsequently verified by phenotypic, pigmental, and structural gene expression analyses in transgenic tobacco lines. As revealed by phylogenetic and alignment analyses, CmMYB4 and CmMYB5 were phenylpropanoid and flavonoid repressor R2R3-MYB genes, respectively, while CmMYB6 was an activator of anthocyanin biosynthesis, and CmMYB7 was involved in regulating flavonol biosynthesis. Compared with wild-type plants, the relative anthocyanin contents in the 35S:CmMYB4 and 35S:CmMYB5 tobacco lines significantly decreased (p < 0.05), while for 35S:CmMYB6 and 35S:CmMYB7, the opposite result was obtained. Both in the 35S:CmMYB4 and 35S:CmMYB5 lines, the relative expression of several anthocyanin biosynthetic genes in tobacco was significantly downregulated (p < 0.05); on the contrary, several genes were upregulated in the 35S:CmMYB6 and 35S:CmMYB7 lines. These results indicate that CmMYB4 and CmMYB5 negatively regulate anthocyanin biosynthesis in chrysanthemum, while CmMYB6 and CmMYB7 play a positive role, which will aid in understanding the complex mechanism regulating floral pigmentation in chrysanthemum and the functional divergence of the R2R3-MYB gene family in higher plants.

Neuropilin-1 (NRP-1) is a transmembrane glycoprotein. As a VEGF co-receptor, NRP1 significantly enhances VEGFR2 signaling and promotes vascular permeability and migration. The purpose of this study was to evaluate the effects of an NRP-1 inhibitor, ATWLPPR peptide, on the early stages of diabetic retinopathy. Eight-week-old male C57BL/6 mice were divided into three groups: a Normal group, a Diabetes (DB) ATWLPPR treatment group and a DB saline group. Electroretinography (ERG), fundus fluorescence angiography (FFA) and leukostasis were examined to evaluate the retinal injury induced by diabetes at the end of the fifth week after STZ injection. Occludin expression and extravasation of albumin were measured to determine the extent of vascular injury. The oxidative stress level and the levels of inflammation-associated proteins were also assayed. The results indicated that treatment with ATWLPPR prevents the abnormal condition of ERG (amplitudes of b-wave decreased and implicit time increased) and vascular injury (occludin degradation and increase in extravasated albumin). These effects were associated with a reduction in the oxidase stress level and the expression of VEGF, GFAP, and ICAM-1. We conclude that ATWLPPR, an NRP-1 inhibitor, may reduce the early retinal damage induced by diabetes by preserving vascular integrity and decreasing the oxidative stress level. Blockade of NRP-1 may be a new therapeutic strategy for the early stages of DR.

Abstract Background Particulate matter exposure (PM) is a cause of aerodigestive disease globally. The destruction of the World Trade Center (WTC) exposed first responders and inhabitants of New York City to WTC-PM and caused obstructive airways disease (OAD), gastroesophageal reflux disease (GERD) and Barrett’s Esophagus (BE). GERD not only diminishes health-related quality of life but also gives rise to complications that extend beyond the scope of BE. GERD can incite or exacerbate allergies, sinusitis, bronchitis, and asthma. Disease features of the aerodigestive axis can overlap, often necessitating more invasive diagnostic testing and treatment modalities. This presents a need to develop novel non-invasive biomarkers of GERD, BE, airway hyperreactivity (AHR), treatment efficacy, and severity of symptoms. Methods Our observational case-cohort study will leverage the longitudinally phenotyped Fire Department of New York (FDNY)-WTC exposed cohort to identify Biomarkers of Airway Disease, Barrett’s and Underdiagnosed Reflux Noninvasively (BAD-BURN). Our study population consists of n = 4,192 individuals from which we have randomly selected a sub-cohort control group (n = 837). We will then recruit subgroups of i. AHR only ii. GERD only iii. BE iv. GERD/BE and AHR overlap or v. No GERD or AHR, from the sub-cohort control group. We will then phenotype and examine non-invasive biomarkers of these subgroups to identify under-diagnosis and/or treatment efficacy. The findings may further contribute to the development of future biologically plausible therapies, ultimately enhance patient care and quality of life. Discussion Although many studies have suggested interdependence between airway and digestive diseases, the causative factors and specific mechanisms remain unclear. The detection of the disease is further complicated by the invasiveness of conventional GERD diagnosis procedures and the limited availability of disease-specific biomarkers. The management of reflux is important, as it directly increases risk of cancer and negatively impacts quality of life. Therefore, it is vital to develop novel noninvasive disease markers that can effectively phenotype, facilitate early diagnosis of premalignant disease and identify potential therapeutic targets to improve patient care. Trial registration Name of Primary Registry: “Biomarkers of Airway Disease, Barrett's and Underdiagnosed Reflux Noninvasively (BADBURN)”. Trial Identifying Number: NCT05216133 . Date of Registration: January 31, 2022.

Abstract In recent years, immunotherapy, particularly PD-1 antibodies, have significantly enhanced the outcome of gastric cancer patients. Despite these advances, some patients do not respond well to treatment, highlighting the need to understand resistance mechanisms and develop predictive markers of treatment effectiveness. This study retrospectively analyzed data from 106 patients with stage IV gastric cancer who were treated with first-line immunotherapy in combination with chemotherapy. By comparing plasma cytokine levels between patients resistant and sensitive to PD-1 antibody therapy, the researchers identified elevated IL-4 expression in the resistant patients. Mechanical investigations revealed that IL-4 induces metabolic changes in macrophages that activate the PI3K/AKT/mTOR pathway. This alteration promotes ATP production, enhances glycolysis, increases lactic acid production, and upregulates FcγRIIB expression in macrophages. Ultimately, these changes lead to CD8+ T cell dysfunction and resistance to PD-1 antibody therapy in gastric cancer. These findings highlight the role of IL-4-induced macrophage polarization and metabolic reprogramming in immune resistance and verify IL-4 as potential targets for improving treatment outcomes in gastric cancer patients.