Long non-coding RNA RAD51-AS1 promotes the tumorigenesis of ovarian cancer by elevating EIF5A2 expression.

PURPOSE: The present study aims to determine the molecular mechanism mediated by RAD51 antisense RNA 1 (RAD51-AS1) in ovarian cancer (OvCA). METHODS: The data associated with RAD51-AS1 in OvCA were obtained from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. Relative expression of RAD51-AS1 was detected. Determination of cell proliferation, metastasis, and invasion was performed by cell counting, colony formation, would-healing, and transwell invasion assays. Protein levels were detected by western blotting. The molecular mechanism mediated by RAD51-AS1 was predicted by bioinformatics analysis and verified by dual-luciferase reporter assays. Subcutaneous tumorigenesis models were used to confirm the function of RAD51-AS1 in vivo. RESULTS: Data from TCGA and GEO showed that RAD51-AS1 was associated with poor prognosis in OvCA patients and DNA repair, cell cycle, focal adhesion, and apoptosis in SKOV3.ip cells. High levels of RAD51-AS1 were detected in OvCA cells. Overexpressing RAD51-AS1 enhanced the proliferative, invading, and migratory capabilities of OvCA cells in vitro while silencing RAD51-AS1 exhibited the opposite effects. Mechanically, RAD51-AS1 elevated eukaryotic initiation factor 5A2 (EIF5A2) expression as a sponge for microRNA (miR)-140-3p. Finally, the role of RAD51-AS1 was verified by subcutaneous tumorigenesis models. CONCLUSION: RAD51-AS1 promoted OvCA progression by the regulation of the miR-140-3p/EIF5A2 axis, which illustrated the potential therapeutic target for OvCA.

Network analysis for inter-relationships of the suboptimal health status with depression and anxiety during the COVID-19 pandemic: A perspective of predictive, preventive, and personalized health.

BACKGROUND: The Coronavirus Disease-2019 (COVID-19) pandemic has had a profound impact on suboptimal health status, depression, and anxiety, necessitating a comprehensive understanding of their inter-relationships at the national level. This study aims to investigate the inter-relationships among suboptimal health status, depression, and anxiety using a network analysis approach. METHODS: We conducted a national survey between June 20 and August 31, 2022. Three network models were constructed and analyzed to independently examine the inter-relationships among suboptimal health status, depression, and anxiety. RESULTS: A total of 26,152 participants were included in this study. The study network analysis indicated that item 9 (i.e., Slow response) exhibited the highest node strength within the suboptimal health status questionnaire-short form (SHSQ-SF) network, followed by item 5 (i.e., Breathlessness at rest). Additionally, positive correlations were observed between depression and anxiety severity and most of the SHSO-SF items. CONCLUSIONS: This study provided valuable insights into inter-relationships between suboptimal health status, depression, and anxiety, informing the development of comprehensive intervention strategies for the general population. These findings have important implications for promoting the well-being and mental health of individuals during and beyond the COVID-19 pandemic.

Spatial distribution of tumor-resident macrophages as predictive biomarkers in endometrial cancer.

BACKGROUND: To investigate the role of CD47 expression and its relationship with tumor-resident macrophages, specifically at the tumor margin, in patients with type II endometrial cancer. This study aims to elucidate whether CD47 could serve as a prognostic marker and to understand the dynamics between CD47 and macrophages, which could inform new therapeutic strategies. METHODS: A retrospective cohort study was conducted involving 75 patients of type II endometrial. Immunohistochemical analysis was performed to assess CD47 expression and macrophage markers (CD68 and CD163). RESULTS: The study found no direct correlation between CD47 expression levels and overall survival (p = 0.32), challenging its role as an independent prognostic marker in type II endometrial cancer. The higher expression of CD47 had significantly less incidence of endometrioid carcinoma G3 (p = 0.047). The negative correlation between CD47 H-score and the density of CD68-positive macrophages at tumor margin was statistically significant (p = 0.049). A high density of CD68-positive macrophages at the tumor margin but a low density of CD163-positive macrophages at the tumor margin were associated with poorer prognosis (p = 0.036). CONCLUSIONS: The complex interaction between CD47 and macrophages, particularly at the tumor margin, suggests new avenues for targeted therapy in type II endometrial cancer.

Organocatalytic enantioselective decarboxylative protonation of α-alkyl-α-aryl malonate monoesters.

In contrast to the well-established enzymatic enantioselective decarboxylative protonation (EDP), the corresponding chemocatalytic reactions of acyclic malonic acid derivatives remain challenging. Herein, we developed a biomimetic EDP of α-alkyl-α-aryl malonate monoesters using a chiral 1,2-trans-diaminocyclohexane-based N-sulfonamide as an organocatalyst. The method demonstrates excellent chemical yields, good enantioselectivity, mild reaction conditions, and the generation of only CO2 as waste.

Rapid screening and identification of targeted and non-targeted illegal added drugs in functional foods by MRSIT-HRMS based on NIST screening database.

The last few decades have witnessed the increasing consumption of functional foods, leading to the expansion of the worldwide market. However, the illegal addition drugs in functional foods remains incessant despite repeated prohibition, making it a key focus of strict crackdowns by regulatory authorities. Effective analytical tools and procedures are desperately needed to rapidly screen and identify illegally added drugs in a large number of samples, given the growing amount and diversity of these substances in functional foods. The MRSIT-HRMS (Multiple Sample Rapid Introduction combined with High Resolution Mass Spectrometry) without chromatographic separation, after direct sampling, utilizes NIST software (National Institute of Standards and Technology) matching with a home-built library to target identification and non-targeted screen of illegal additives. When applied to 50 batches of suspicious samples, the targeted method detected illegal added drugs in 41 batches of samples, while the non-targeted method screened a new phosphodiesterase-5 (PDE-5) inhibitor type structural derivative. The positive results obtained by the targeted method were consistent with LC-MS/MS (QQQ). The novel MRSIT-HRMS with a limit of quantification (LOD) of 1 µg/mL achieved 100 % correct identification for all 50 batches of actual samples, demonstrating its potential as a highly promising and powerful tool for fast screening of illegally added drugs in functional food, especially when compared to traditional LC-MS/MS methods. This is essential for ensuring drug safety and public health.

An enhanced cardio-protective effect of nanoparticles loaded with active components from Polygonum orientale L. against isoproterenol-induced myocardial ischemia in rats.

In this study, nanoparticles loaded with active components from Polygonum orientale L. (PO), a traditional Chinese herb known for its anti-myocardial ischemic properties, were investigated for cardio-protective properties. Specifically, OVQ-Nanoparticles (OVQ-NPs) with Orientin (Ori), Vitexin (Vit), and Quercetin (Que) was obtained by double emulsion-solvent evaporation method. The OVQ-NPs exhibited a spherical shape, with a uniform size distribution of 136.77 ± 3.88 nm and a stable ζ-potential of -13.40 ± 2.24 mV. Notably, these nanoparticles exhibited a favorable sustained-release characteristic, resulting in an extended circulation time within the living organism. Consequently, the administration of these nanoparticles resulted in significant improvements in electrocardiograms and heart mass index of myocardial ischemic rats induced by isoproterenol, as well as decreased serum levels of CK, LDH, and AST. Furthermore, the results of histopathological examination, such as H&E staining and TUNEL staining, confirmed a reduced level of cardiac tissue pathology and apoptosis. Moreover, the quantification of biochemical indicators (SOD, MDA, GSH, NO, TNF-α, and IL-6) demonstrated that OVQ-NPs effectively mitigated myocardial ischemia by regulating oxidative stress and inflammatory pathways. In conclusion, OVQ-NPs demonstrate promising therapeutic potential as an intervention for myocardial ischemia, providing a new perspective on traditional Chinese medicine treatment in this area.

High-efficiency upconversion luminescence in UCNPs/CsPbBr3 nanocomposites enhanced by silver nanoparticles.

Upconversion nanocomposites with multiple light-emitting centers have attracted great attention as functional materials, but their low efficiency limits their further applications. Herein, a novel, to the best of our knowledge, system for nanocomposites consisting of upconversion nanoparticles (UCNPs) and perovskite quantum dots (PeQDs) assembled with Ag nanoparticles (NPs) is proposed. Upconversion luminescence (UCL) operation from PeQDs is triggered by near-infrared (NIR) sensitization through Förster resonance energy transfer (FRET) and photon reabsorption (PR). Especially, the photoluminescence (PL) emission efficiency is found to be significantly enhanced due to the increased energy transfer efficiency and radiative decay rate in the UCNPs/CsPbBr3 nanocomposites. The results offer new opportunities to improve the UCL properties of perovskites and open new development in the fields of LED lighting, solar cells, biomedicine, and so on.

Quantification of preexisting lung ground glass opacities on CT for predicting checkpoint inhibitor pneumonitis in advanced non-small cell lung cancer patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can lead to life-threatening pneumonitis, and pre-existing interstitial lung abnormalities (ILAs) are a risk factor for checkpoint inhibitor pneumonitis (CIP). However, the subjective assessment of ILA and the lack of standardized methods restrict its clinical utility as a predictive factor. This study aims to identify non-small cell lung cancer (NSCLC) patients at high risk of CIP using quantitative imaging. METHODS: This cohort study involved 206 cases in the training set and 111 cases in the validation set. It included locally advanced or metastatic NSCLC patients who underwent ICI therapy. A deep learning algorithm labeled the interstitial lesions and computed their volume. Two predictive models were developed to predict the probability of grade ≥ 2 CIP or severe CIP (grade ≥ 3). Cox proportional hazard models were employed to analyze predictors of progression-free survival (PFS). RESULTS: In a training cohort of 206 patients, 21.4% experienced CIP. Two models were developed to predict the probability of CIP based on different predictors. Model 1 utilized age, histology, and preexisting ground glass opacity (GGO) percentage of the whole lung to predict grade ≥ 2 CIP, while Model 2 used histology and GGO percentage in the right lower lung to predict grade ≥ 3 CIP. These models were validated, and their accuracy was assessed. In another exploratory analysis, the presence of GGOs involving more than one lobe on pretreatment CT scans was identified as a risk factor for progression-free survival. CONCLUSIONS: The assessment of GGO volume and distribution on pre-treatment CT scans could assist in monitoring and manage the risk of CIP in NSCLC patients receiving ICI therapy. CLINICAL RELEVANCE STATEMENT: This study's quantitative imaging and computational analysis can help identify NSCLC patients at high risk of CIP, allowing for better risk management and potentially improved outcomes in those receivingICI treatment.

Decreasing the incidence of delirium via multi-sensory stimulation in patients receiving mechanical ventilation in the intensive care unit: A protocol for a randomized feasibility study.

Introduction: Delirium is a common acute brain dysfunction syndrome in patients admitted to intensive care units (ICUs). Family engagement strategies, based on the theory of multi-sensory stimulation to ameliorate sensory deprivation in patients, may be an effective and scalable method to reduce the burden of delirium. Methods: /design: This is a assessor-blinded, randomised controlled trial of the feasibility of multi-sensory stimulation (MS) in patients with delirium. A total of 72 mechanically ventilated patients (n = 24 in each group) admitted to the ICU will be randomised to routine non-pharmacological delirium care (control), family multi-sensory stimulation and nurse multi-sensory stimulation groups. All participants except the control group will receive multi-sensory stimulation, including visual, auditory, tactile and kinesthetic stimulation, for 5 days. Our primary aim is to determine the feasibility of the study procedure (recruitment, eligibility, retention and attrition rates, appropriateness of clinical outcome measures), feasibility, acceptability and safety of the intervention (adverse events, satisfaction and other). Our secondary objective is to assess the preliminary efficacy of the MS protocol in reducing the incidence, duration and severity of delirium. Sedation levels and delirium severity will be assessed twice daily. Enrolled participants will be followed in hospital until death, discharge or up to 28 days after treatment. Ethics and dissemination: The current study was approved by the Ethics Review Board of Huazhong University of Science and Technology Union Shenzhen Hospital, China (KY-2023-031-01). The results of this study will be presented at scientific conferences and submitted for publication in peer-reviewed journals. Trial registration number: ChiCTR2300071457.

Comparison of the EPDS and PHQ-9 in the assessment of depression among pregnant women: Similarities and differences.

BACKGROUND: Perinatal depression has attracted increasing attention. However, a detailed investigation of the network structure of depression is still lacking. We aim to examine the similarities and differences between the Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire (PHQ-9) from a network perspective. METHODS: A cross-sectional study was conducted from August 2020 to March 2022. We followed the STROBE checklist to report our research. Pregnant women (n = 2484) were recruited. All participants completed the EPDS and PHQ-9. We mainly used network analyses for statistical analysis and constructed two network models: the EPDS and PHQ-9 models. RESULTS: The detection rates of prenatal depression measured by the EPDS and PHQ-9 were 30.2 % and 28.2 %, respectively. In the EPDS network, the EPDS8 'sad or miserable' node (strength = 1.2161) was the most central node, and the EPDS10 'self-harming' node (strength = 0.4360) was the least central node. In the PHQ-9 network, the PHQ4 'fatigue' node (strength = 0.9815) was the most central node, and PHQ9 'suicide' was the least central symptom (strength = 0.5667). For both models, 'sad' acted as an important central symptom. CONCLUSIONS: Psychological symptoms may be more important in assessing depression using the EPDS, while physical symptoms may be more influential in assessing depression using the PHQ-9. For both the EPDS and PHQ-9, "sad" was an important central symptom, suggesting that it may be the most important target for further maternal depression interventions in the future.

Single nucleotide polymorphism SNP19140160 A > C is a potential breeding locus for fast-growth largemouth bass (Micropterus salmoides).

BACKGROUND: Largemouth bass (Micropterus salmoides) has significant economic value as a high-yielding fish species in China's freshwater aquaculture industry. Determining the major genes related to growth traits and identifying molecular markers associated with these traits serve as the foundation for breeding strategies involving gene pyramiding. In this study, we screened restriction-site associated DNA sequencing (RAD-seq) data to identify single nucleotide polymorphism (SNP) loci potentially associated with extreme growth differences between fast-growth and slow-growth groups in the F1 generation of a largemouth bass population. RESULTS: We subsequently identified associations between these loci and specific candidate genes related to four key growth traits (body weight, body length, body height, and body thickness) based on SNP genotyping. In total, 4,196,486 high-quality SNPs were distributed across 23 chromosomes. Using a population-specific genotype frequency threshold of 0.7, we identified 30 potential SNPs associated with growth traits. Among the 30 SNPs, SNP19140160, SNP9639603, SNP9639605, and SNP23355498 showed significant associations; three of them (SNP9639603, SNP9639605, and SNP23355498) were significantly associated with one trait, body length, in the F1 generation, and one (SNP19140160) was significantly linked with four traits (body weight, height, length, and thickness) in the F1 generation. The markers SNP19140160 and SNP23355498 were located near two growth candidate genes, fam174b and ppip5k1b, respectively, and these candidate genes were closely linked with growth, development, and feeding. The average body weight of the group with four dominant genotypes at these SNP loci in the F1 generation population (703.86 g) was 19.63% higher than that of the group without dominant genotypes at these loci (588.36 g). CONCLUSIONS: Thus, these four markers could be used to construct a population with dominant genotypes at loci related to fast growth. These findings demonstrate how markers can be used to identify genes related to fast growth, and will be useful for molecular marker-assisted selection in the breeding of high-quality largemouth bass.

Monkeypox: Can we count on the current smallpox immunization?

Two vaccines ACAM 2000 and JYNNEOS have obtained approval from the Food and Drug Administration as preventive measures against monkeypox, contributing significantly to the management of the monkeypox epidemic. Nonetheless, research has demonstrated that smallpox vaccination offers approximately 88.8% protection against monkeypox, while immunization with these vaccines generates relatively low levels of neutralizing antibodies. In this work, we performed a comprehensive comparison of antigens between the 2022-2023 monkeypox strains and the smallpox vaccine strains. Our analysis has revealed considerable amino acid changes in all 27 antigens, including core and envelope proteins. Amino acid substitutions within B cell epitopes were observed in 26 of these antigens, with at least half of the antigen substitutions occurring within B cell epitopes in 20 out of the 26 antigens analyzed. These findings may raise potential concerns regarding the efficacy of these vaccines.

The impact of internet health information seeking on COVID-19 vaccination behavior in China.

BACKGROUND: Amid the COVID-19 pandemic, the significance of vaccination has been emphatically underscored. As the foremost and pivotal measure for preventing COVID-19 transmission, the COVID-19 pneumonia vaccine plays an instrumental role in the global response to this infectious respiratory disease. However, COVID-19 vaccination coverage remains challenging in low- and middle-income countries and regions. Studies have found that frequent seeking to health information is also associated with healthier behaviors, but these studies have not yet focused on the impact of Internet health information seeking on individual vaccination and the mechanism of this effect. METHODS: Data were obtained from the Chinese General Social Survey (CGSS) conducted in 2021, which included 7,218 individual samples. This study used COVID-19 vaccination as indicators for the health of interest, the key independent variable is Internet health information seeking. This study tried to analyze the impact of Internet health information seeking on COVID-19 vaccination using an OLS model and PSM method. RESULTS: The results show that Internet health information seeking has a significant positive impact on COVID-19 vaccination. This result passed a series of robustness tests. The mechanism analysis indicated that compared to non-Internet health information seeking individuals, Internet health information seeking individuals could know the superior advantages of vaccination and the potential for immunization through this method. And individuals who use Internet to seeking health information are more likely to acknowledge the constructive impact of online information on health behavior. This helps to explain why Internet health information seeking individuals have a higher rate of COVID-19 vaccination. CONCLUSIONS: This study delves into the influence of Internet health information seeking on individual COVID-19 vaccination within the digital era. The outcomes underscore that Internet-mediated seeking vaccine information holds the potential to bolster individuals' comprehension of vaccination benefits and foster increased acceptance of such information.

Emission characteristics and removal of heavy metals in flue gas: a case study in waste incineration and coal-fired power plants.

Heavy metal pollutants such as Hg, As, Pb, Cr, and Cd emitted from coal and waste combustion have received widespread attention. In this study, we systematically investigated the emission characteristics of heavy metals in waste incineration and coal-fired flue gases, focused on testing the removal effect of self-made cold electrode electrostatic precipitator (CE-ESP) on heavy metals in flue gas, and made a comparative analysis with the existing air pollution control devices (APCDs). Test results from waste incineration power plant showed that each APCD showed a certain effect on the removal of heavy metals in condensable particulate matter (CPM), with an average removal efficiency of bag filter was 86%, but its effect on Hg removal was slightly worse. Under the coupled field with electrified cold electrode plate operation mode, the average removal efficiency of CE-ESP on heavy metals in CPM was as high as 93%, including 76% for Hg. The removal efficiency of heavy metals (especially Hg) in CPM increased with the increase of flue gas temperature difference between inlet and outlet of CE-ESP. Test results from this coal-fired power plant showed that heavy metals were enriched in fly ash to a higher degree than in slag, the synergistic control of heavy metals in submicron particulate matter by the dust remover was not obvious, and there was a significant correlation between each heavy metal emission factor and its content in coal. Under the temperature field with non-electric cold electrode plate operation mode, the overall effect of CE-ESP on the removal of gaseous heavy metals was better than that of particulate heavy metals. Under the conventional electric field operation mode, CE-ESP was less effective in removing particulate Cr and gaseous Hg0. Under the coupled field with electrified cold electrode plate operation mode, the average removal efficiencies of CE-ESP for particulate and gaseous heavy metals were 82.37% and 76.16%, respectively.

Comprehensive analysis the prognostic and immune characteristics of mitochondrial transport-related gene SFXN1 in lung adenocarcinoma.

BACKGROUND: Mitochondria, which serve as the fundamental organelle for cellular energy and metabolism, are closely linked to the growth and survival of cancer cells. This study aims to identify and assess Sideroflexin1 (SFXN1), an unprecedented mitochondrial gene, as a potential prognostic biomarker for lung adenocarcinoma (LUAD). METHODS: The mRNA and protein levels of SFXN1 were investigated based on the Cancer Genome Atlas (TCGA) LUAD dataset, and then validated by real-time quantitative PCR, Western Blotting and immunohistochemistry from our clinical samples. The clinical correlation and prognostic value were evaluated by the TCGA cohort and verified via our clinical dataset (n = 90). The somatic mutation, drug sensitivity data, immune cell infiltration and single-cell RNA sequencing data of SFXN1 were analyzed through public databases. RESULTS: SFXN1 was markedly upregulated at both mRNA and protein levels in LUAD, and high expression of SFXN1 were correlated with larger tumor size, positive lymph node metastasis, and advanced clinical stage. Furthermore, SFXN1 upregulation was significantly associated with poor clinical prognosis. SFXN1 co-expressed genes were also analyzed, which were mainly involved in the cell cycle, central carbon metabolism, DNA repair, and the HIF-1α signaling pathway. Additionally, SFXN1 expression correlated with the expression of multiple immunomodulators, which act to regulate the tumor immune microenvironment. Results also demonstrated an association between SFXN1 expression and increased immune cell infiltration, such as activated CD8 + T cells, natural killer cells (NKs), activated dendritic cells (DCs), and macrophages. LUAD patients with high SFXN1 expression exhibited heightened sensitivity to multiple chemotherapies and targeted drugs and predicted a poor response to immunotherapy. SFXN1 represented an independent prognostic marker for LUAD patients with an improved prognostic value for overall survival when combined with clinical stage information. CONCLUSIONS: SFXN1 is frequently upregulated in LUAD and has a significant impact on the tumor immune environment. Our study uncovers the potential of SFXN1 as a prognostic biomarker and as a novel target for intervention in LUAD.

Benzyl Deuteriodifluoromethyl Sulfoxide: An Easily Accessible and Stable Reagent for Direct Deuterodifluoromethylthiolation.

A new, stable and scalable reagent based on a sulfoxide skeleton for direct deuteriodifluoromethylthiolation has been developed. The reagent displays excellent reactivities toward Tf2O promoted C-H deuteriodifluoromethylthiolation of electron-rich arenes, indoles, alkenes, and intramolecular lactonization of 2-alkynylbenzoates. Moreover, high deuteration rates and good to excellent yields were achieved under metal-free reaction conditions. As a result, a wide range of deuteriodifluoromethylthilolated compounds were prepared, enabling further applications in drug discovery.

Functional brain network alterations in the co-occurrence of autism spectrum disorder and attention deficit hyperactivity disorder.

Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are two highly prevalent and commonly co-occurring neurodevelopmental disorders. The neural mechanisms underpinning the comorbidity of ASD and ADHD (ASD + ADHD) remain unclear. We focused on the topological organization and functional connectivity of brain networks in ASD + ADHD patients versus ASD patients without ADHD (ASD-only). Resting-state functional magnetic resonance imaging (rs-fMRI) data from 114 ASD and 161 typically developing (TD) individuals were obtained from the Autism Brain Imaging Data Exchange II. The ASD patients comprised 40 ASD + ADHD and 74 ASD-only individuals. We constructed functional brain networks for each group and performed graph-theory and network-based statistic (NBS) analyses. Group differences between ASD + ADHD and ASD-only were analyzed at three levels: nodal, global, and connectivity. At the nodal level, ASD + ADHD exhibited topological disorganization in the temporal and occipital regions, compared with ASD-only. At the global level, ASD + ADHD and ASD-only displayed no significant differences. At the connectivity level, the NBS analysis revealed that ASD + ADHD showed enhanced functional connectivity between the prefrontal and frontoparietal regions, as well as between the orbitofrontal and occipital regions, compared with ASD-only. The hippocampus was the shared region in aberrant functional connectivity patterns in ASD + ADHD and ASD-only compared with TD. These findings suggests that ASD + ADHD displays altered topology and functional connectivity in the brain regions that undertake social cognition, language processing, and sensory processing.

Rice kinase OsMRLK63 contributes to drought tolerance by regulating reactive oxygen species production.

Drought is a major adverse environmental factor that plants face in nature but the molecular mechanism by which plants transduce stress signals and further endow themselves with tolerance remains unclear. Malectin/malectin-like domains containing receptor-like kinases (MRLKs) have been proposed to act as receptors in multiple biological signaling pathways, but limited studies show their roles in drought-stress signaling and tolerance. In this study, we demonstrate OsMRLK63 in rice (Oryza sativa L.) functions in drought tolerance by acting as the receptor of 2 rapid alkalization factors, OsRALF45 and OsRALF46. We show OsMRLK63 is a typical receptor-like kinase that positively regulates drought tolerance and reactive oxygen species (ROS) production. OsMRLK63 interacts with and phosphorylates several nicotinamide adenine dinucleotide phosphate (NADPH) oxidases with the primarily phosphorylated site at Ser26 in the N-terminal of RESPIRATORY BURST OXIDASE HOMOLOGUE A (OsRbohA). The application of the 2 small signal peptides (OsRALF45/46) on rice can greatly alleviate the dehydration of plants induced by mimic drought. This function depends on the existence of OsMRLK63 and the NADPH oxidase-dependent ROS production. The 2 RALFs interact with OsMRLK63 by binding to its extracellular domain, suggesting they may act as drought/dehydration signal sensors for the OsMRLK63-mediated process. Our study reveals a OsRALF45/46-OsMRLK63-OsRbohs module which contributes to drought-stress signaling and tolerance in rice.

Schaftoside reduces inflammation in Aspergillus fumigatus keratitis through the inhibition of the TLR4/MyD88 pathway.

PURPOSE: The purpose of this research study was to investigate the impact of schaftoside on Aspergillus fumigatus (A. fumigatus) keratitis and elucidate its underlying mechanisms. METHODS: In order to establish safe experimental concentrations of schaftoside in human corneal epithelial cells (HCECs), RAW264.7 cells, and mouse models, various techniques were employed including cytotoxicity assay (CCK-8) assay, cell scratch assay, and Draize test. The therapeutic effect of schaftoside was assessed using slit-lamp biomicroscopy, clinical scores, as well as determination of neutrophil infiltration through hematoxylin and eosin (HE) staining, immunofluorescence (IF) staining, and myeloperoxidase (MPO) assay. The levels of Toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), pro-inflammatory mediators interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and IL-6 were determined using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and IF techniques. RESULTS: Schaftoside at a concentration of 160 µM displayed no harmful side effects on HCECs, RAW cells, and mouse corneas, rendering it suitable for further experiments. In a murine fungal keratitis model, schaftoside mitigated the severity of fungal keratitis by inhibiting neutrophil infiltration and reducing MPO activity. Both in vitro and in vivo experiments demonstrated that schaftoside treatment suppressed the upregulation of IL-1ß, TNF-α, and IL-6 expression, while also downregulating the expressions of TLR4 as well as MyD88 at both mRNA and protein levels. CONCLUSIONS: Schaftoside demonstrated a protective effect against A. fumigatus keratitis by reducing corneal damage through inhibition of neutrophil recruitment and downstream inflammatory cytokines. The anti-inflammatory properties of schaftoside in A. fumigatus keratitis may involve modulation of the TLR4/MyD88 pathway.

Robinin inhibits pancreatic cancer cell proliferation, EMT and inflammation via regulating TLR2-PI3k-AKT signaling pathway.

PURPOSE: To investigate the anti-tumor effect of Robinin (Toll-like receptor 2 inhibitor) in pancreatic cancer cells via regulating tumor microenvironment. METHODS: The effects of Robinin on cell proliferation or migration in Mia-PACA2 and PANC-1 were determined, using CCK8 or wound healing assay, respectively. The typical markers of EMT (αSMA and snail) and the inflammation markers (IL-6 and TNF-α) were all detected by western blot. CU-T12-9 (TLR2 agonist) was used to rescue Robinin's effect. PI3k-p85α and Phosphorylated-AKT (p-AKT) were evaluated, compared to the ß-actin and AKT, using western blot. RESULTS: Robinin significantly inhibited cell proliferation and migration in Mia-PACA2 and PANC-1, compared to HPNE (**P < 0.01). Robinin also attenuated the expression of α-SMA and snail in Mia-PACA2, and PANC-1 (**P < 0.01). Besides, it was found that expression of IL-6 and TNF-α were diminished in presence of Robinin in Mia-PACA2, and PANC-1 (**P < 0.01). Western blot confirmed that Robinin could target on TLR2, and further downregulated PI3k-AKT signaling pathway to exert biological function. CONCLUSIONS: Robinin exerts anti-tumor effect perhaps via downregulating inflammation and EMT in pancreatic cancer cell through inhibiting TLR2-PI3k-AKT signaling pathway. Robinin may be a novel agent in adjuvant therapy of pancreatic cancer.