M2 Macrophage-Derived sEV Regulate Pro-Inflammatory CCR2+ Macrophage Subpopulations to Favor Post-AMI Cardiac Repair.

Tissue-resident cardiac macrophage subsets mediate cardiac tissue inflammation and repair after acute myocardial infarction (AMI). CC chemokine receptor 2 (CCR2)-expressing macrophages have phenotypical similarities to M1-polarized macrophages, are pro-inflammatory, and recruit CCR2+ circulating monocytes to infarcted myocardium. Small extracellular vesicles (sEV) from CCR2̶ macrophages, which phenotypically resemble M2-polarized macrophages, promote anti-inflammatory activity and cardiac repair. Here, the authors harvested M2 macrophage-derived sEV (M2EV ) from M2-polarized bone-marrow-derived macrophages for intramyocardial injection and recapitulation of sEV-mediated anti-inflammatory activity in ischemic-reperfusion (I/R) injured hearts. Rats and pigs received sham surgery; I/R without treatment; or I/R with autologous M2EV treatment. M2EV rescued cardiac function and attenuated injury markers, infarct size, and scar size. M2EV inhibited CCR2+ macrophage numbers, reduced monocyte-derived CCR2+ macrophage recruitment to infarct sites, induced M1-to-M2 macrophage switching and promoted neovascularization. Analysis of M2EV microRNA content revealed abundant miR-181b-5p, which regulated macrophage glucose uptake, glycolysis, and mitigated mitochondrial reactive oxygen species generation. Functional blockade of miR-181b-5p is detrimental to beneficial M2EV actions and resulted in failure to inhibit CCR2+ macrophage numbers and infarct size. Taken together, this investigation showed that M2EV rescued myocardial function, improved myocardial repair, and regulated CCR2+ macrophages via miR-181b-5p-dependent mechanisms, indicating an option for cell-free therapy for AMI.

SlIAA23-SlARF6 module controls arbuscular mycorrhizal symbiosis by regulating strigolactone biosynthesis in tomato.

Auxins are a class of phytohormones with roles involved in the establishment and maintenance of the arbuscular mycorrhizal symbiosis (AMS). Auxin response factors (ARFs) and Auxin/Indole-acetic acids (AUX/IAAs), as two transcription factors of the auxin signaling pathway, coregulate the transcription of auxin response genes. However, the interrelation and regulatory mechanism of ARFs and AUX/IAAs in regulating AMS are still unclear. In this study, we found that the content of auxin in tomato roots increased sharply and revealed the importance of the auxin signaling pathway in the early stage of AMS. Notably, SlARF6 was found to play a negative role in AMF colonization. Silencing SlARF6 significantly increased the expression of AM-marker genes, as well as AMF-induced phosphorus uptake. SlIAA23 could interact with SlARF6 in vivo and in vitro, and promoted the AMS and phosphorus uptake. Interestingly, SlARF6 and SlIAA23 played a contrary role in strigolactone (SL) synthesis and accumulation in AMF-colonized roots of tomato plants. SlARF6 could directly bind to the AuxRE motif of the SlCCD8 promoter and inhibited its transcription, however, this effect was attenuated by SlIAA23 through interaction with SlARF6. Our results suggest that SlIAA23-SlARF6 coregulated tomato-AMS via an SL-dependent pathway, thus affecting phosphorus uptake in tomato plants.

Complete Genome Sequence of Streptomyces sp. HP-A2021, a Promising Bacterium for Natural Product Discovery.

Streptomyces are one of the most prolific sources of bioactive and structurally diverse secondary metabolites for natural product drug discovery. Genome sequencing and bioinformatics analysis revealed that the genomes of Streptomyces harbor a wealth of cryptic secondary metabolite biosynthetic gene clusters that could encode novel compounds. In this work, a genome mining approach was employed to investigate the biosynthetic potential of Streptomyces sp. HP-A2021, isolated from rhizosphere soil of Ginkgo biloba L. The complete genome of HP-A2021 was sequenced and contained the 9,607,552 base pair linear chromosome with a GC content of 71.07%. The annotation results revealed the presence of 8534 CDSs, 76 tRNA genes, and 18 rRNA genes in HP-A2021. The highest dDDH and ANI values based on genome sequences between HP-A2021 and the most closely related type strain, Streptomyces coeruleorubidus JCM 4359, were 64.2% and 92.41%, respectively. In total, 33 secondary metabolite biosynthetic gene clusters with an average length of 105,594 bp were identified, including the putative thiotetroamide, alkylresorcinol, coelichelin, and geosmin. The antibacterial activity assay confirmed that the crude extracts of HP-A2021 showed potent antimicrobial activity against human pathogenic bacteria. Our study demonstrated that Streptomyces sp. HP-A2021 will propose a potential use in biotechnological and novel bioactive secondary metabolite biosynthetic applications.

SUMO1 regulates post-infarct cardiac repair based on cellular heterogeneity.

Small ubiquitin-related modifier (SUMOylation) is a dynamic post-translational modification that maintains cardiac function and can protect against a hypertrophic response to cardiac pressure overload. However, the function of SUMOylation after myocardial infarction (MI) and the molecular details of heart cell responses to SUMO1 deficiency have not been determined. In this study, we demonstrated that SUMO1 protein was inconsistently abundant in different cell types and heart regions after MI. However, SUMO1 knockout significantly exacerbated systolic dysfunction and infarct size after myocardial injury. Single-nucleus RNA sequencing revealed the differential role of SUMO1 in regulating heart cells. Among cardiomyocytes, SUMO1 deletion increased the Nppa + Nppb + Ankrd1 + cardiomyocyte subcluster proportion after MI. In addition, the conversion of fibroblasts to myofibroblasts subclusters was inhibited in SUMO1 knockout mice. Importantly, SUMO1 loss promoted proliferation of endothelial cell subsets with the ability to reconstitute neovascularization and expressed angiogenesis-related genes. Computational analysis of ligand/receptor interactions suggested putative pathways that mediate cardiomyocytes to endothelial cell communication in the myocardium. Mice preinjected with cardiomyocyte-specific AAV-SUMO1, but not the endothelial cell-specific form, and exhibited ameliorated cardiac remodeling following MI. Collectively, our results identified the role of SUMO1 in cardiomyocytes, fibroblasts, and endothelial cells after MI. These findings provide new insights into SUMO1 involvement in the pathogenesis of MI and reveal novel therapeutic targets.

Dysregulated low-density granulocyte contributes to early spontaneous abortion.

Spontaneous abortion (SA) is a common adverse pregnancy event with unclarified pathogenesis and limited therapeutic efficiency. Although most SA cases with the euploid embryo(s) are associated with immunological factors, the contribution of low-density granulocyte (LDG) in SA pathogenesis is rarely reported. This study aimed to investigate the serial characteristics and possible contribution of LDG and their subpopulations in early pregnancy, especially in early SA. Unpregnant (UP), normally pregnant (NP), and SA women were recruited, and the peripheral blood and endometrium/decidua were collected for LDG isolation and histological observation. The percentage, phenotype, and subpopulations of LDG were analyzed via flow cytometric analysis, and the ability of Nets formation was assessed by immunofluorescent and immunohistochemical assays. As a result, 43 participants were enrolled, including 10 UP, 15 NP, and 18 SA women. Compared with the UP group, the LDG percentage in peripheral blood mononuclear cells (PBMCs) and decidual immune cells (DICs) increased in the NP group, while the loss of this increase was observed in the SA group. Meanwhile, CD16int/- cell percentage in peripheral blood LDG (PB-LDG) increased in the NP and SA groups, and insufficient activation of CD16hi PB-LDG characterized by reduced CD11b expression was discovered in the SA group. Moreover, the LDG percentage in DICs was higher than that in PBMCs, and the decidual LDG (D-LDG) showed a surface marker expression profile that is easier to be activated in the pregnant cohort (NP + SA women). Finally, increased decidual Nets formation was observed in the SA group compared with the NP group, and more Nets formation was detected in D-LDG of NP and SA women following PMA stimulation. Overall, LDG participates in the maintenance of early pregnancy, while dysregulated LDG is responsible for early SA, providing novel potential targets for further exploration of SA pathogenesis and therapeutics.

Assessing vaccine literacy and exploring its association with vaccine hesitancy: A validation of the vaccine literacy scale in China.

BACKGROUND: Assessment of vaccine literacy is essential for understanding people's ability to access various vaccine information to meet health demands. Few studies have examined the role of vaccine literacy in vaccine hesitancy, which is a psychological state. This study aimed to validate the applicability of the HLVa-IT (Vaccine Health Literacy of Adults in Italian) scale in Chinese settings and to explore the association between vaccine literacy and vaccine hesitancy. METHODS: From May to June 2022, we conducted an online cross-sectional survey in mainland China. Potential factor domains were obtained by the exploratory factor analysis. Cronbach's alpha coefficient, composite reliability values, and square root values of average variances extracted were calculated to determine the internal consistency and discriminant validity. The association between vaccine literacy, vaccine acceptance, with vaccine hesitancy was assessed using logistic regression analysis. RESULTS: Totally, 12,586 participants completed the survey. Two potential dimensions, the functional and the interactive/critical, were identified. Cronbach's alpha coefficient and composite reliability values were >0.90. The square root values of average variances extracted exceeded the related correlations. The functional dimension (adjusted odds ratio (aOR): 0579; 95 % Confidence Interval (CI); 0.529, 0.635), interactive (aOR: 0.654; 95%CI: 0.531, 0.806)/critical (aOR: 0.709; 95%CI: 0.575, 0.873) dimension were significantly and negatively associated with vaccine hesitancy. Similar results were also found in different vaccines acceptance subgroups. LIMITATIONS: This report is limited by the convenience sampling method. CONCLUSIONS: The modified HLVa-IT is suitable for use in Chinese settings. Vaccine literacy was negatively associated with vaccine hesitancy.

Willingness to Vaccinate Against Herpes Zoster and Its Associated Factors Across WHO Regions: Global Systematic Review and Meta-Analysis.

BACKGROUND: A life-course immunization approach would enhance the quality of life across all age groups and improve societal well-being. The herpes zoster (HZ) vaccine is highly recommended for older adults to prevent HZ infection and related complications. The proportions of willingness to receive the HZ vaccine varies across countries, and various kinds of factors, including sociodemographics and individual perceptions, influence the willingness to vaccinate. OBJECTIVE: We aim to estimate the HZ vaccination willingness rate and identify factors associated with vaccine uptake willingness across all World Health Organization (WHO) regions. METHODS: A global systematic search was performed on PubMed, Web of Science, and the Cochrane Library for all papers related to the HZ vaccine published until June 20, 2022. Study characteristics were extracted for each included study. Using double arcsine transformation, vaccination willingness rates with 95% CIs were pooled and reported. The willingness rate and associated factors were analyzed by geographical context. Associated factors were also summarized based on Health Belief Model (HBM) constructs. RESULTS: Of the 26,942 identified records, 13 (0.05%) papers were included, covering 14,066 individuals from 8 countries in 4 WHO regions (Eastern Mediterranean Region, European Region, Region of the Americas, and Western Pacific Region). The pooled vaccination willingness rate was 55.74% (95% CI 40.85%-70.13%). Of adults aged ≥50 years, 56.06% were willing to receive the HZ vaccine. After receiving health care workers' (HCWs) recommendations, 75.19% of individuals were willing to get the HZ vaccine; without HCWs' recommendations, the willingness rate was only 49.39%. The willingness rate was more than 70% in the Eastern Mediterranean Region and approximately 55% in the Western Pacific Region. The willingness rate was the highest in the United Arab Emirates and the lowest in China and the United Kingdom. The perception of HZ severity and susceptibility was positively associated with vaccination willingness. The perceived barriers to vaccination willingness (main reasons for unwillingness) included low trust in the effectiveness of the HZ vaccine, concerns about safety, financial concerns, and being unaware of the HZ vaccine's availability. Older individuals, those having lower education, or those having lower income levels were less likely to willing to be vaccinated. CONCLUSIONS: Only 1 in 2 individuals showed a willingness to be vaccinated against HZ. The willingness rate was the highest in the Eastern Mediterranean Region. Our findings show the critical role HCWs play in promoting HZ vaccination. Monitoring HZ vaccination willingness is necessary to inform public health decision-making. These findings provide critical insights for designing future life-course immunization programs.

Cyanidin-3-O-Glucoside Rescues Zearalenone-Induced Apoptosis via the ITGA7-PI3K-AKT Signaling Pathway in Porcine Ovarian Granulosa Cells.

Zearalenone (ZEN) is an important secondary metabolite of Fusarium fungi, exposure to which can cause reproductive disorders through its effects on ovarian granulosa cells (GCs) in many mammals, especially in pigs. This study aimed to investigate the protective effects of Cyanidin-3-O-glucoside (C3G) on the ZEN-induced negative effects in porcine GCs (pGCs). The pGCs were treated with 30 µM ZEN and/or 20 µM C3G for 24 h; they were divided into a control (Ctrl) group, ZEN group, ZEN+C3G (Z+C) group, and a C3G group. Bioinformatics analysis was used to systematically screen differentially expressed genes (DEGs) in the rescue process. Results showed that C3G could effectively rescue ZEN-induced apoptosis in pGCs, and notably increase cell viability and proliferation. Furthermore, 116 DEGs were identified, and the phosphatidylinositide 3-kinases-protein kinase B (PI3K-AKT) signaling pathway was the center of attention, of which five genes and the PI3K-AKT signaling pathway were confirmed by real-time quantitative PCR (qPCR) and/or Western blot (WB). As analyzed, ZEN inhibited mRNA and protein levels of integrin subunit alpha-7 (ITGA7), and promoted the expression of cell cycle inhibition kinase cyclin-D3 (CCND3) and cyclin-dependent kinase inhibitor 1 (CDKN1A). After the knock-down of ITGA7 by siRNA, the PI3K-AKT signaling pathway was significantly inhibited. Meanwhile, proliferating cell nuclear antigen (PCNA) expression decreased, and apoptosis rates and pro-apoptotic proteins increased. In conclusion, our study demonstrated that C3G exhibited significant protective effects on the ZEN-induced inhibition of proliferation and apoptosis via the ITGA7-PI3K-AKT pathway.

Comparison of Over-the-Scope Clips to Standard Endoscopic Treatment as the Initial Treatment in Patients With Bleeding From a Nonvariceal Upper Gastrointestinal Cause : A Randomized Controlled Trial.

BACKGROUND: Current endoscopic methods in the control of acute nonvariceal bleeding have a small but clinically significant failure rate. The role of over-the-scope clips (OTSCs) as the first treatment has not been defined. OBJECTIVE: To compare OTSCs with standard endoscopic hemostatic treatments in the control of bleeding from nonvariceal upper gastrointestinal causes. DESIGN: A multicenter, randomized controlled trial. (ClinicalTrials.gov: NCT03216395). SETTING: University teaching hospitals in Hong Kong, China, and Australia. PATIENTS: 190 adult patients with active bleeding or a nonbleeding visible vessel from a nonvariceal cause on upper gastrointestinal endoscopy. INTERVENTION: Standard hemostatic treatment (n = 97) or OTSC (n = 93). MEASUREMENTS: The primary outcome was 30-day probability of further bleeds. Other outcomes included failure to control bleeding after assigned endoscopic treatment, recurrent bleeding after initial hemostasis, further intervention, blood transfusion, and hospitalization. RESULTS: The 30-day probability of further bleeding in the standard treatment and OTSC groups was 14.6% (14 of 97) and 3.2% (3 of 93), respectively (risk difference, 11.4 percentage points [95% CI, 3.3 to 20.0 percentage points]; P = 0.006). Failure to control bleeding after assigned endoscopic treatment in the standard treatment and OTSC groups was 6 versus 1 (risk difference, 5.1 percentage points [CI, 0.7 to 11.8 percentage points]), respectively, and 30-day recurrent bleeding was 8 versus 2 (risk difference, 6.6 percentage points [CI, -0.3 to 14.4 percentage points]), respectively. The need for further interventions was 8 versus 2, respectively. Thirty-day mortality was 4 versus 2, respectively. In a post hoc analysis with a composite end point of failure to successfully apply assigned treatment and further bleeds, the event rate was 15 of 97 (15.6%) and 6 of 93 (6.5%) in the standard and OTSC groups, respectively (risk difference, 9.1 percentage points [CI, 0.004 to 18.3 percentage points]). LIMITATION: Clinicians were not blinded to treatment and the option of crossover treatment. CONCLUSION: Over-the-scope clips, as an initial treatment, may be better than standard treatment in reducing the risk for further bleeding from nonvariceal upper gastrointestinal causes that are amenable to OTSC placement. PRIMARY FUNDING SOURCE: General Research Fund to the University Grant Committee, Hong Kong SAR Government.

Effect of Substituent Location on the Relationship between the Transition Dipole Moments, Difference Static Dipole, and Hydrophobicity in Squaraine Dyes for Quantum Information Devices.

Aggregates of organic dyes that exhibit excitonic coupling have a wide array of applications, including medical imaging, organic photovoltaics, and quantum information devices. The optical properties of a dye monomer, as a basis of dye aggregate, can be modified to strengthen excitonic coupling. Squaraine (SQ) dyes are attractive for those applications due to their strong absorbance peak in the visible range. While the effects of substituent types on the optical properties of SQ dyes have been previously examined, the effects of various substituent locations have not yet been investigated. In this study, density functional theory (DFT) and time-dependent density functional theory (TD-DFT) were used to investigate the relationships between SQ substituent location and several key properties of the performance of dye aggregate systems, namely, difference static dipole (Δd), transition dipole moment (µ), hydrophobicity, and the angle (θ) between Δd and µ. We found that attaching substituents along the long axis of the dye could increase µ while placement off the long axis was shown to increase Δd and reduce θ. The reduction in θ is largely due to a change in the direction of Δd as the direction of µ is not significantly affected by substituent position. Hydrophobicity decreases when electron-donating substituents are located close to the nitrogen of the indolenine ring. These results provide insight into the structure-property relationships of SQ dyes and guide the design of dye monomers for aggregate systems with desired properties and performance.

Three-Dimensional Evaluation Effects of Microimplant-Assisted Rapid Palatal Expansion on the Upper Airway Volume: A Systematic Review and Meta-Analysis.

Microimplant-assisted rapid palatal expansion is increasingly used clinically; however, the effect on the upper airway volume in patients with maxillary transverse deficiency has not been thoroughly evaluated yet. The following electronic databases were searched up to August 2022: Medline via Ovid, Scopus, Embase, Web of Science, Cochrane Library, Google Scholar, and ProQuest. The reference lists of related articles were also reviewed by manual search. The Revised Cochrane Risk of Bias Tool for randomized trials (ROB2) and the Risk of Bias in non-randomized Studies of Interventions (ROBINS-I) tool were used to evaluate the risks of bias of the included studies. The mean differences (MD) and 95% confidence intervals (CI) of changes in nasal cavity and upper airway volume were analyzed using a random-effects model, and subgroup and sensitivity analyses were also performed. Two reviewers independently completed the process of screening studies, extracting data, and assessing the quality of studies. In total, twenty-one studies met the inclusion criteria. After assessing the full texts, only thirteen studies were included, with nine studies selected for quantitative synthesis. Oropharynx volume increased significantly after immediate expansion (WMD: 3156.84; 95% CI: 83.63, 6230.06); however, there was no significant change in nasal volume (WMD: 2527.23; 95% CI: -92.53, 5147.00) and nasopharynx volume (WMD: 1138.29; 95% CI: -52.04, 2328.61). After retention a period, significant increases were found in nasal volume (WMD: 3646.27; 95% CI: 1082.77, 6209.77) and nasopharynx volume (WMD: 1021.10; 95% CI: 597.11, 1445.08). However, there was no significant change after retention in oropharynx volume (WMD: 789.26; 95% CI: -171.25, 1749.76), palatopharynx volume (WMD: 795.13; 95% CI: -583.97, 2174.22), glossopharynx volume (WMD: 184.50; 95% CI: -1745.97, 2114.96), and hypopharynx volume (WMD: 39.85; 95% CI: -809.77, 889.46). MARPE appears to be linked with long-term increases in nasal and nasopharyngeal volume. However, high-quality clinical trials are required to further verify the effects of MARPE treatment on the upper airway.

Krüppel-like factor 15 in liver diseases: Insights into metabolic reprogramming.

Liver diseases, characterized by metabolic disorder, have become a global public health problem with high morbidity and mortality. Krüppel-like factor 15 (KLF15) is a zinc-finger transcription factor mainly enriched in liver. Increasing evidence suggests that hepatic KLF15 is activated rapidly during fasting, and contributes to the regulation of gluconeogenesis, lipid, amino acid catabolism, bile acids, endobiotic and xenobiotic metabolism. This review summarizes the latest advances of KLF15 in metabolic reprogramming, and explore the function of KLF15 in acute liver injury, hepatitis B virus, and autoimmune hepatitis. which aims to evaluate the potential of KLF15 as a therapeutic target and prognostic biomarker for liver diseases.

GLSP and GLSP-derived triterpenes attenuate atherosclerosis and aortic calcification by stimulating ABCA1/G1-mediated macrophage cholesterol efflux and inactivating RUNX2-mediated VSMC osteogenesis.

Background and Purpose: Atherosclerosis is the main pathophysiological foundation of cardiovascular disease, which was caused by inflammation and lipid metabolism disorder, along with vascular calcification. Aortic calcification leads to reduced plaque stability and eventually causes plaque rupture which leads to cardiovascular events. Presently, the drug to treat aortic calcification remains not to be available. Ganoderma lucidum spore powder (GLSP) is from Ganoderma lucidum which is a Traditional Chinese Medicine with the homology of medicine and food. It has multiple pharmacological effects, but no research on aortic calcification during atherosclerosis was performed. This study investigated the effects of GLSP on atherosclerosis and aortic calcification and revealed the underlying mechanism. Methods: In vivo, 8-week-aged male LDLR-/- mice were fed a high-fat diet to induce atherosclerosis along with aortic calcification. Simultaneously, the mice were treated with GLSP at the first week of HFD feeding to determine the protection against early and advanced atherosclerosis. Subsequently, the mice tissues were collected to evaluate the effects of GLSP on atherosclerosis, and aortic calcification, and to reveal the underlying mechanism. In vitro, we determined the major components of GLSP triterpenes by HPLC, and subsequently assessed the protective effects of these main active components on lipid metabolism, inflammation, and calcification in RAW264.7 and HASMC cells. Results: We observed GLSP attenuated plaque area and aortic calcification in the mice with early and advanced atherosclerosis. GLSP reduced the number of foam cells by improving ABCA1/G1-mediated cholesterol efflux in macrophages. In addition, GLSP protected against the aortic endothelium activation. Moreover, GLSP inhibited aortic calcification by inactivating RUNX2-mediated osteogenesis in HASMCs. Furthermore, we determined the major components of GLSP triterpenes, including Ganoderic acid A, Ganoderic acid B, Ganoderic acid C6, Ganoderic acid G, and Ganodermanontriol, and found that these triterpenes promoted ABCA1/G1-mediated cholesterol efflux and inhibited inflammation in macrophage, and inactivated RUNX2-mediated osteogenesis in VSMC. Conclusions: This study demonstrates that GLSP attenuates atherosclerosis and aortic calcification by improving ABCA1/G1-mediated cholesterol efflux and inactivating RUNX2-mediated osteogenesis in LDLR-/- mice. GLSP may be a potential drug candidate for the treatment of atherosclerosis and vascular calcification.

Molecular superglue-mediated higher-order assembly of TRAIL variants with superior apoptosis induction and antitumor activity.

Prompting higher-order death receptor (DR) clustering by increasing the valency of DR agonist is efficient to induce apoptosis of tumor cells. As an attractive DR agonist with superior biosafety, the trimeric tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) exerts limited antitumor effect in patients, which is predominantly attributed to its low DR clustering ability and short serum half-life. Previous antibody scaffolds-based engineering strategies to increase the valency and/or prolong the serum half-life of TRAIL improve apoptosis induction, however, often produce large proteins with poor tumor penetration. Covalent protein ligation mediated by small molecular superglues such as SpyTag/SpyCatcher might be a novel strategy to assemble higher-order TRAIL variants. Upon fusion to TRAIL promotor, SpyTag/SpyCatcher molecular superglue preferentially ligated two trimeric TRAIL to produce a hexameric TRAIL variant, HexaTR, exhibiting a significantly increased apoptosis induction. In addition, an albumin-binding HexaTR, ABD-HexaTR, with a prolonged serum half-life by binding to endogenous albumin was also produced using the same strategy. Compared to the trimeric TRAIL, the hexameric HexaTR and ABD-HexaTR showed 20-50 times greater in vivo antitumor effect, resulting in eradication of several types of large (150-300 mm3) tumor xenografts. Combination with bortezomib carried by liposome further improved the antitumor effects of the hexavalent HexaTR and ABD-HexaTR in refractory cancer. Our results indicate that the superglue-mediated higher-order assembly is promising to improve the DR clustering and proapoptotic signaling of TRAIL, showing great advantages in constructing the next generation of DR agonists for cancer therapy.

Molecular Dynamic Studies of Dye-Dye and Dye-DNA Interactions Governing Excitonic Coupling in Squaraine Aggregates Templated by DNA Holliday Junctions.

Dye molecules, arranged in an aggregate, can display excitonic delocalization. The use of DNA scaffolding to control aggregate configurations and delocalization is of research interest. Here, we applied Molecular Dynamics (MD) to gain an insight on how dye-DNA interactions affect excitonic coupling between two squaraine (SQ) dyes covalently attached to a DNA Holliday junction (HJ). We studied two types of dimer configurations, i.e., adjacent and transverse, which differed in points of dye covalent attachments to DNA. Three structurally different SQ dyes with similar hydrophobicity were chosen to investigate the sensitivity of excitonic coupling to dye placement. Each dimer configuration was initialized in parallel and antiparallel arrangements in the DNA HJ. The MD results, validated by experimental measurements, suggested that the adjacent dimer promotes stronger excitonic coupling and less dye-DNA interaction than the transverse dimer. Additionally, we found that SQ dyes with specific functional groups (i.e., substituents) facilitate a closer degree of aggregate packing via hydrophobic effects, leading to a stronger excitonic coupling. This work advances a fundamental understanding of the impacts of dye-DNA interactions on aggregate orientation and excitonic coupling.

Identification and Comparative Expression Profiles of Candidate Olfactory Receptors in the Transcriptomes of the Important Egg Parasitoid Wasp Anastatus japonicus Ashmead (Hymenoptera: Eupelmidae).

Anastatus japonicus Ashmead is an egg parasitoid wasp important for the biological control of fruit crop pests. The olfaction of parasitoids is crucial to searching for host pests in fruit crops. In this study, we sequenced and analyzed the antennal and abdominal transcriptomes of A. japonicus to better understand the olfactory mechanisms in this species. A total of 201 putative olfactory receptor genes were identified, including 184 odorant receptors (ORs) and 17 ionotropic receptors (IRs). Then, we assayed the tissue-specific and sex-biased expression profiles of those genes based on the transcriptional levels. In total, 165 ORs and 15 IRs had upregulated expression in the antennae. The expression levels of 133 ORs, including odorant receptor co-receptor (AjapORco), and 10 IRs, including AjapIR8a, were significantly different between the female and male antennae. Our results provide valuable information for further studies on the molecular mechanisms of the olfactory system in A. japonicus.

Embedded racetrack microring resonator sensor based on GeSbSe glasses.

In this article, a compact racetrack double microring resonator (MRR) sensor based on Ge28Sb12Se60 (GeSbSe) is investigated. The sensor device consists of a racetrack microring, an embedded small microring, and a strip waveguide. Electron beam lithography (EBL) and dry etching are used to fabricate the device. The compact racetrack double MRR device are obtained with Q-factor equal to 7.17 × 104 and FSR of 24 nm by measuring the transmission spectrum. By measuring different concentrations of glucose solutions, a sensitivity of 297 nm/RIU by linear fitting and an intrinsic limit of detection (iLOD) of 7.40 × 10-5 are obtained. It paves the way for the application of chalcogenide glasses in the field of biosensing.

LECT2 modulates dendritic cell function after Helicobacter pylori infection via the CD209a receptor.

BACKGROUND: Helicobacter pylori, a gram-negative bacterium persisting on the gastric mucosa, is involved in the pathogenesis of a variety of gastric diseases. Leukocyte cell-derived chemotaxin 2 (LECT2) treatment increased the phagocytic capacity of lymphocytes and improved immune function in bacterial infection. Whether the immune cells infected with H. pylori are affected by LECT2 is unclear. METHODS: Bone marrow-derived dendritic cells (BMDCs) from wild-type C57BL/6 mice, CD209a knockout mice, or LECT2 knockout mice were exposed to H. pylori at a multiplicity of infection of 10 for 24 h. The maturity of DCs and the cytokines secreted by DCs were analyzed by flow cytometry, western blot, and real-time PCR. The signaling pathway underlying CD209a activation after LECT2 treatment were also detected. RESULTS: LECT2 treatment promoted H. pylori-induced BMDC maturation and produced a high level of anti-inflammatory cytokine (IL-10) but a low level of pro-inflammatory cytokine (IL-23p40). Moreover, LECT2-pretreated DCs shifted the development of pro-inflammatory Th1/Th17 cells to Treg cells. CD209a mediated LECT2-induced maturation and secretion of DC in H. pylori-primed BMDCs. LECT2 was further confirmed to induce the secretion of certain cytokines via CD209a-JNK/P38 MAPK pathway. CONCLUSION: This study reveals that LECT2 modulated the functions of H. pylori-primed DCs in a CD209a-dependent manner, which might hinder the clearance of H. pylori and contribute to its colonization.

Cardamonin alleviates chondrocytes inflammation and cartilage degradation of osteoarthritis by inhibiting ferroptosis via p53 pathway.

Osteoarthritis (OA) is a common degenerative joint disease, mainly presented by the deterioration of articular cartilage. Amounts of data demonstrated this deterioration is composed of oxidative stress, pro-inflammation and chondrocyte death events. Ferroptosis is a novel form of cell death that differs from apoptosis and autophagy, recent studies have shown that chondrocyte ferroptosis contributes to the development of osteoarthritis. Cardamonin (CAD) has been demonstrated to possess antioxidant and anti-inflammatory properties in several diseases, whether CAD may influence the OA progression is still obscure. Therefore, we aimed to determine whether CAD alleviates chondrocyte ferroptosis and its effect on OA with potential mechanism. In this study, we found that inflammation, cartilage degradation and ferroptosis induced by interleukin-1ß (IL-1ß) were significantly alleviated by CAD. Moreover, the administration of the ferroptosis inhibitor, Deferoxamine (DFO) reversed the inflammatory and cartilage degradation effects of IL-1ß as well. Chondrocyte mitochondrial morphology and function were alleviated by both CAD and DFO. We found that CAD increased collagen II, p53, SLC7A11 GPX4 expression and decreased MMP13, iNOS, COX2 expression in chondrocytes, further investigation showed that the P53 signaling pathway was involved. In vivo, intra-articular injection of CAD significantly ameliorated cartilage damage in a rat OA model, induced collagen II and SLC7A11 expression by immunohistochemistry. Our study proves that CAD ameliorated OA cartilage degradation by regulating ferroptosis via P53 signaling pathway, suggesting a potential role of CAD in OA treatment.