Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2.

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.

Nanozyme-Inhibited SERS Multichannel Paper-Based Sensor Array for the Quantification and Identification of Biothiols and Cancer Cells Based on Three Ag-Based Nanomaterials.

Biothiols play essential roles in maintaining normal physiological functions, resisting oxidative stress, and protecting cell health. Establishing an effective and reliable sensor array for the accurate quantification and discrimination of diverse biothiols is extremely meaningful. In this work, Ag/Mn3O4, Ag3PO4, and Ag3Cit with excellent oxidase-mimetic activity and surface-enhanced Raman scattering (SERS)-enhanced features have been prepared and loaded onto Whatman filter paper (WFP) to build SERS paper chips as three sensing channels, which can induce 3,3',5,5'-tetramethylbenzidine (TMB) oxidation to SERS-active reporters (TMBox) and concurrently generate prominent SERS signals. Nevertheless, the addition of biothiols can suppress conversion from TMB to TMBox, which can cause the reduction of the SERS signal from TMBox. Interestingly, each SERS sensing channel can generate different TMBox signals' variations due to differences in the oxidative inhibition abilities of diverse biothiols and exclusive properties of each paper chip, which can be plotted as specific fingerprint patterns of each biothiol and further translated into intuitive two-dimensional (2D) clustering profiles through linear discriminant analysis (LDA) and hierarchical cluster analysis (HCA) techniques for precise identification of these six biothiols with the minimum concentration of 1 µM. More importantly, this SERS sensor array is exploited for the precise quantification of intracellular glutathione (GSH), and can differentiate between normal and cancer cells based on different intracellular GSH contents and even identify different types of tumor cells, demonstrating its powerful application prospects in disease diagnosis.

Long non-coding RNA RP11-197K6.1 as ceRNA promotes colorectal cancer progression via miR-135a-5p/DLX5 axis.

BACKGROUND: Colorectal cancer (CRC) remains a major global health challenge, with high incidence and mortality rates. The role of long noncoding RNAs (lncRNAs) in cancer progression has received considerable attention. The present study aimed to investigate the function and mechanisms underlying the role of lncRNA RP11-197K6.1, microRNA-135a-5p (hsa-miR-135a-5p), and DLX5 in CRC development. METHODS: We analyzed RNA sequencing data from The Cancer Genome Atlas Colorectal Cancer dataset to identify the association between lncRNA RP11-197K6.1 and CRC progression. The expression levels of lncRNA RP11-197K6.1 and DLX5 in CRC samples and cell lines were determined by real-time quantitative PCR and western blotting assays. Fluorescence in situ hybridization was used to confirm the cellular localization of lncRNA RP11-197K6.1. Cell migration capabilities were assessed by Transwell and wound healing assays, and flow cytometry was performed to analyze apoptosis. The interaction between lncRNA RP11-197K6.1 and miR-135a-5p and its effect on DLX5 expression were investigated by the dual-luciferase reporter assay. Additionally, a xenograft mouse model was used to study the in vivo effects of lncRNA RP11-197K6.1 on tumor growth, and an immunohistochemical assay was performed to assess DLX5 expression in tumor tissues. RESULTS: lncRNA RP11-197K6.1 was significantly upregulated in CRC tissues and cell lines as compared to that in normal tissues, and its expression was inversely correlated with patient survival. It promoted the migration and metastasis of CRC cells by interacting with miR-135a-5p, alleviated suppression of DLX5 expression, and facilitated tumor growth. CONCLUSION: This study demonstrated the regulatory network and mechanism of action of the lncRNA RP11-197K6.1/miR-135a-5p/DLX5 axis in CRC development. These findings provided insights into the molecular pathology of CRC and suggested potential therapeutic targets for more effective treatment of patients with CRC.

Room-temperature efficient and tunable interlayer exciton emissions in WS2/WSe2 heterobilayers at high generation rates.

Transition metal dichalcogenide (TMDC) heterobilayers (HBs) have been intensively investigated lately because they offer novel platforms for the exploration of interlayer excitons (IXs). However, the potentials of IXs in TMDC HBs have not been fully studied as efficient and tunable emitters for both photoluminescence (PL) and electroluminescence (EL) at room temperature (RT). Also, the efficiencies of the PL and EL of IXs have not been carefully quantified. In this work, we demonstrate that IX in WS2/WSe2 HBs could serve as promising emitters at high generation rates due to its immunity to efficiency roll-off. Furthermore, by applying gate voltages to balance the electron and hole concentrations and to reinforce the built-in electric fields, high PL quantum yield (QY) and EL external quantum efficiency (EQE) of ∼0.48% and ∼0.11% were achieved at RT, respectively, with generation rates exceeding 1021 cm-2·s-1, which confirms the capabilities of IXs as efficient NIR light emitters by surpassing most of the intralayer emissions from TMDCs.

Discovery of 1,2,3-triazole-based pleuromutilin derivatives as potent gram-positive antibacterial agents.

A novel class of pleuromutilin derivatives possessing 1,2,3-triazole as the linker connected to phenyl analogues were designed. The antibacterial properties of the prepared compounds were assessed in vitro against five strains (E. coli, S. aureus, S. epidermidis, and E. faecalis). Most of the tested compounds displayed potent antibacterial activities against gram-positive bacteria and 14-O-[2-(4-((2,4-dinitrophenoxy)-methyl-1H-1,2,3-triazol-1-yl) acetamide)-2-methylpropan-2-yl) thioacetyl]mutilin (7c) exerted antibacterial activities against S. aureus, MRSA and S. epidermidis with MIC values 0.0625 µg/mL, representing 64-fold, 4-fold and 8-fold higher than tiamulin respectively. Compound 6e, 7c and 8c were chosen to carry out killing kinetics, which exhibited concentration-dependent effect. Subsequently, molecular modeling was conducted to further explore the binding of compound 6e, 7a, 7c, 8c and tiamulin with 50S ribosomal subunit from deinococcus radiodurans. The investigation revealed that the main interactions between compound 7c and the ribosomal residues were three hydrogen bonds, π-π, and p-π conjugate effects. Additionally, the free binding energy and docking score of 7c with the ribosome demonstrated the lowest values of -11.90 kcal/mol and -7.97 kcal/mol, respectively, consistent with its superior antibacterial activities.

Spatiotemporal connectivity maps abnormal communication pathways in major depressive disorder underlying gamma oscillations.

Auditory steady-state response underlying gamma oscillations (gamma-ASSR) have been explored in patients with major depressive disorder (MDD), while ignoring the spatiotemporal dynamic characteristics. This study aims to construct dynamic directed brain networks to explore the disruption of spatiotemporal dynamics underlying gamma-ASSR in MDD. This study recruited 29 MDD patients and 30 healthy controls for a 40 Hz auditory steady-state evoked experiment. The propagation of gamma-ASSR was divided into early, middle, and late time interval. Partial directed coherence was applied to construct dynamic directed brain networks based on graph theory. The results showed that MDD patients had lower global efficiency and out-strength in temporal, parietal, and occipital regions over three time intervals. Additionally, distinct disrupted connectivity patterns occurred in different time intervals with abnormalities in the early and middle gamma-ASSR in left parietal regions cascading forward to produce dysfunction of frontal brain regions necessary to support gamma oscillations. Furthermore, the early and middle local efficiency of frontal regions were negatively correlated with symptom severity. These findings highlight patterns of hypofunction in the generation and maintenance of gamma-band oscillations across parietal-to-frontal regions in MDD patients, which provides novel insights into the neuropathological mechanism underlying gamma oscillations associated with aberrant brain network dynamics of MDD.

Valorization of treated swine wastewater and generated biomass by microalgae: Their effects and salt tolerance mechanisms on wheat seedling growth.

The extensive use of mineral fertilizers has a negative impact on the environment, whereas wastewater and microalgal biomass can provide crops with nutrients such as nitrogen, phosphorus, and potassium, and have the potential to be used as a source of fertilizers in circular agriculture. In this study, a step-by-step resource utilization study of algae-containing wastewater generated from microalgae treatment of swine wastewater was carried out. When wheat seedlings were cultivated in the effluent after microalgae separation, the root fresh weight, seedling fresh weight, and total seedling length were increased by 3.44%, 14.45%, and 13.64%, respectively, compared with that of the algae-containing wastewater, and there was no significant difference in seedling fresh weight, total seedling length, maximum quantum yields of PSII photochemistry (Fv/Fm), and performance index (PIABS) from that of the Hogland solution group, which has the potential to be an alternative liquid fertilizer. Under salt stress, microalgae extract increased the contents of GA3, IAA, ABA, and SA in wheat seedlings, antioxidant enzymes maintained high activity, and the PIABS value increased. Low-dose microalgae extract (1 mL/L) increased the root fresh weight, seedling fresh weight, longest seedling length, and total seedling length by 30.73%, 31.28%, 16.43%, and 28.85%, respectively. Algae extract can act as a plant biostimulant to regulate phytohormone levels to attenuate the damage of salt stress and promote growth.

Development and validation of a nomogram for individualizing fall risk in patients with hematologic malignancies.

Inpatient falls are common adverse events especially for patients with hematologic malignancies. A fall-risk prediction model for patients with hematologic malignancies are still needed. Here we conducted a multicenter study that prospectively included 516 hospitalized patients with hematologic malignancies, and developed a nomogram for fall risk prediction. Patients were divided into the modeling group (n = 389) and the validation group (n = 127). A questionnaire containing sociodemographic factors, general health factors, disease-related factors, medication factors, and physical activity factors was administered to all patients. Logistic regression analysis revealed that peripheral neuropathy, pain intensity, Morse fall scale score, chemotherapy courses, and myelosuppression days were risk factors for falls in patients with hematologic malignancies. The nomogram model had a sensitivity of 0.790 and specificity of 0.800. The calibration curves demonstrated acceptable agreement between the predicted and observed outcomes. Therefore, the nomogram model has promising accuracy in predicting fall risk in patients with hematologic malignancies.

The Combination of Quantitative Proteomics and Systems Genetics Analysis Reveals that PTN Is Associated with Sleep-Loss-Induced Cognitive Impairment.

Sleep loss is associated with cognitive dysfunction. However, the detailed mechanisms remain unclear. In this study, we established a para-chlorophenylalanine (PCPA)-induced insomniac mouse model with impaired cognitive function. Mass-spectrometry-based proteomics showed that the expression of 164 proteins was significantly altered in the hippocampus of the PCPA mice. To identify critical regulators among the potential markers, a transcriptome-wide association screening was performed in the BXD mice panel. Among the candidates, the expression of pleiotrophin (Ptn) was significantly associated with cognitive functions, indicating that Ptn-mediates sleep-loss-induced cognitive impairment. Gene co-expression analysis further revealed the potential mechanism by which Ptn mediates insomnia-induced cognitive impairment via the MAPK signaling pathway; that is, the decreased secretion of Ptn induced by insomnia leads to reduced binding to Ptprz1 on the postsynaptic membrane with the activation of the MAPK pathway via Fos and Nr4a1, further leading to the apoptosis of neurons. In addition, Ptn is genetically trans-regulated in the mouse hippocampus and implicated in neurodegenerative diseases in human genome-wide association studies. Our study provides a novel biomarker for insomnia-induced cognitive impairment and a new strategy for seeking neurological biomarkers by the integration of proteomics and systems genetics.

miR-449a ameliorates acute rejection after liver transplantation via targeting procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 in macrophages.

Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.

Effect of Preparation Processes on Structural Thermal Stability and Collision Energy Dissipation of Common Antirelaxation Coatings on Quartz Substrates.

Paraffin and octadecyltrichlorosilane (OTS) coatings can alleviate collisions between alkali-metal atoms and cell walls and then prolong the atomic spin-polarization lifetime. The surface structure and collision effects of these antirelaxation coatings, as well as the methods to avoid antirelaxation invalidity, have been the focus of researchers. This study investigated the thermolability of coating surface structure and the collision interactions between alkali metal atoms and coatings, considering the influence of various coating preparation factors, where this collision interaction is indirectly analyzed by measuring the collision energy dissipation between an atomic force microscopy (AFM) probe and the atoms on the coating surface. We found that appropriate evaporation time, carbochain length, and postannealing process can enhance the thermostability of the paraffin coating and eliminate its morphological defects. Furthermore, the OTS/water concentration, the soaking time, and the type of solvent have different levels of influence on the cluster formation and the thermostability of the OTS coatings. Moreover, the antirelaxation performance of coatings has been shown to be characterized by counting the energy dissipated when the AFM probe collides with the antirelaxation coating, replacing the conventional light-atom interaction- based method for measuring the relaxation characteristics, but requiring specific coating preparation factors to be maintained.

Probable rivaroxaban-induced erythema multiforme in children: A case report.

Background: Limited data exists on the use of rivaroxaban for the treatment of pediatric patients. This report presents a case of probable rivaroxaban-induced Erythema Multiforme in Children. Case Summary: A female patient aged 5.5 years with antiphospholipid syndrome (APS) was administered oral rivaroxaban tablets 2.5 mg twice a day for 16 days. Subsequently, the patient developed a slight itching sensation on both feet and buttocks without an apparent cause. The following day, erythema multiforme appeared across the body in a scattered pattern. The erythema presented higher than the skin surface and partially merged into areas of the skin. Following an increase in the extent and degree of the erythema, all oral medications were ceased. Treatment with dexamethasone sodium phosphate injection, mometasone furoate cream, and mucopolysaccharide polysulfate cream resulted in an improvement of erythema multiforme. The erythema diminished and did not deteriorate subsequent to changing from rivaroxaban tablets to warfarin sodium tablets, and receiving nadroparin calcium injection.

The value of artificial intelligence and imaging diagnosis in the fight against COVID-19.

The outbreak of the new type of coronavirus pneumonia (COVID-19) has caused a huge impact on the world. In this case, only by adhering to the prevention and control methods of early diagnosis, early isolation, and early treatment, can the spread of the virus be prevented to the greatest extent. This article uses artificial intelligence-assisted medical imaging diagnosis as the research object, combines artificial intelligence and CT medical imaging diagnosis, introduces an intelligent COVID-19 detection system, and uses it to achieve COVID-19 disease screening and lesion evaluation. CT examination has the advantages of fast speed and high accuracy, which can provide a favorable basis for clinical diagnosis. This article collected 32 lung CT scan images of patients with confirmed COVID-19. Two professional radiologists analyzed the CT images using traditional imaging diagnostic methods and artificial intelligence-assisted imaging diagnostic methods, and the comparison showed the gap between the two methods. According to experiments, CT imaging diagnosis assisted by artificial intelligence only takes 0.744 min on average, which can save a lot of time and cost compared with the average time of 3.623 min for conventional diagnosis. In terms of comprehensive test accuracy, it can be concluded that the combination of artificial intelligence and imaging diagnosis has extremely high application value in COVID-19 diagnosis.

A Versatile Platform for Sensitive and Label-Free Identification of Biomarkers through an Exo-III-Assisted Cascade Signal Amplification Strategy.

The development of a versatile and sensitive analytical biomarker detection platform is important for both early diagnosis and treatment of diseases. In the present study, we propose a novel fluorescence-based, ultrasensitive, and label-free biomarker detection platform. This platform relies on a flexible probe design compatible for multiple biomarker identification and Exo-III enzyme-triggered cascade signal amplification. We have validated that this label-free platform exhibits high sensitivity and specificity. Indeed, this platform exhibited brilliant analytical performance in qualifying a carcinoembryonic antigen and small extracellular vesicles (sEVs). It also shows excellent capability in multiplexing mapping of surface proteins of various cancer-derived sEVs. Therefore, we believe that the proposed sensing platform has great potential for clinical diagnosis and anticancer drug development.

Fabrication of dual anti-corrosive polyaniline microcapsules via Pickering emulsion for active corrosion protection of steel.

A novel kind of inhibitor-loaded polyaniline (PANI) microcapsule was prepared by Pickering emulsion photopolymerization using polyaniline particles as the Pickering emulsifier. In our strategy, water-dispersible polyaniline nanoparticles were firstly synthesized using a micelle template method and used to stabilize oil-in-water emulsions, in which the oil phase contained photo-crosslinkable and pH sensitive monomers and a photo-initiator. Under UV light, the pH-responsive monomers underwent photo-polymerization and crosslinking and converted to microcapsule shells. During this process, polyaniline nanoparticles were trapped in the microcapsule shells, leading to the formation of PANI microcapsules. The structure and morphology of the synthesized PANI microcapsules were analyzed using FTIR spectroscopy, SEM, and EDX mapping. The inhibitor (mercaptobenzothiazole, MBT) was subsequently incorporated into the PANI microcapsule as a functional core and demonstrated pH-sensitive releasing behavior. With the anti-corrosive PANI as the microcapsule wall and the inhibitor MBT as the core, the as-prepared MBT loaded PANI (MBT@PANI) microcapsule could afford dual corrosion protection, allowing smart protection of metals when exposed to corrosive conditions. The MBT@PANI microcapsules were embedded in UV-cured coating for protecting steel. The corrosion protection performance of the coating with MBT@PANI microcapsules was evaluated using the electrochemical impedance spectroscopy technique and salt spray test, which demonstrated the synergistic inhibition effect of the PANI wall and the loaded MBT in improving anti-corrosion performance of the coating.

Evaluation of anti-tick efficiency in rabbits induced by DNA vaccines encoding Haemaphysalis longicornis lipocalin homologue.

Haemaphysalis longicornis is an obligate haematophagous ectoparasite, transmitting a variety of pathogens, which brings great damage to human health and animal husbandry development. Lipocalins (LIP) are a family of proteins that transport small hydrophobic molecules and also involve in immune regulation, such as the regulation of cell homeostasis, inhibiting the host's inflammatory response and resisting the contractile responses in host blood vessels. Therefore, it is one of the candidate antigens for vaccines. Based on previous studies, we constructed the recombinant plasmid pcDNA3.1-HlLIP of LIP homologue from H. longicornis (HlLIP). ELISA results showed that rabbits immunized with pcDNA3.1-HlLIP produced higher anti-rHlLIP antibody levels compared with the pcDNA3.1 group, indicating that pcDNA3.1-HlLIP induced the humoral immune response of host. Adult H. longicornis infestation trial in rabbits demonstrated that the engorgement weight, oviposition and hatchability of H. longicornis fed on rabbits immunized with pcDNA3.1-HlLIP decreased by 7.07%, 14.30% and 11.70% respectively, compared with that of the pcDNA3.1 group. In brief, DNA vaccine of pcDNA3.1-HlLIP provided immune protection efficiency of 30% in rabbits. This study demonstrated that pcDNA3.1-HlLIP can partially protect rabbits against H. longicornis, and it is possible to develop a new candidate antigen against ticks.

Dual-Targeting Nanoprobe for Early Diagnosis of Pheochromocytoma Though Coinstantaneous Identification of Circulating Tumor Cells.

Circulating tumor cells (CTCs) play a pivotal role in the early diagnosis of pheochromocytoma (PCC). Herein, we fabricated a new dual-targeting nanoprobe for coinstantaneous identification of rare PCC-CTCs from peripheral blood via targeting the norepinephrine transporter (NET) and somatostatin receptor SSTR2 overexpressed on the surface of PCC cells. Meta-iodobenzylguanidine (MIBG) functionalized magnetic Fe3O4 and octreotide (DOTA) decorated signal amplification Ag@SiO2 nanosphere were used to capture and detect PCC-CTCs by binding to NET and SSTR2. The proposed dual-targeting sensor achieved good reproducibility and high sensitivity for the monitoring of PC12 in the concentration range from 5 to 5 × 104 cells mL-1, with detection limits of 2 cell/mL. This strategy opens a new approach for simple, sensitive, and rapid determination of PCC biomarkers, which shows great potential in early diagnosis, prognosis, and therapeutic evaluation of PCC.

Altered spontaneous neural activity in the precuneus, middle and superior frontal gyri, and hippocampus in college students with subclinical depression.

BACKGROUND: Subclinical depression (ScD) is a prevalent condition associated with relatively mild depressive states, and it poses a high risk of developing into major depressive disorder (MDD). However, the neural pathology of ScD is still largely unknown. Identifying the spontaneous neural activity involved in ScD may help clarify risk factors for MDD and explore treatment strategies for mild stages of depression. METHODS: A total of 34 ScD subjects and 40 age-, sex-, and education-matched healthy controls were screened from 1105 college students. The amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of resting-state fMRI were calculated to reveal neural activity. Strict statistical strategies, including Gaussian random field (GRF), false discovery rate (FDR), and permutation test (PT) with threshold-free cluster enhancement (TFCE), were conducted. Based on the altered ALFF and ReHo, resting-state functional connectivity (RSFC) was further analyzed using a seed-based approach. RESULTS: The right precuneus and left middle frontal gyrus (MFG) both showed significantly increased ALFF and ReHo in ScD subjects. Moreover, the left hippocampus and superior frontal gyrus (SFG) showed decreased ALFF and increased ReHo, respectively. In addition, ScD subjects showed increased RSFC between MFG and hippocampus compared to healthy controls, and significant positive correlation was found between the Beck Depression Inventory-II (BDI-II) score and RSFC from MFG to hippocampus in ScD group. CONCLUSION: Spontaneous neural activities in the right precuneus, left MFG, SFG, and hippocampus were altered in ScD subjects. Functional alterations in these dorsolateral prefrontal cortex and default mode network regions are largely related to abnormal emotional processing in ScD, and indicate strong associations with brain impairments in MDD, which provide insight into potential pathophysiology mechanisms of subclinical depression.

IQGAP1/ERK regulates fear memory formation via histone posttranslational modifications induced by HDAC2.

Epigenetic mechanisms of learning and memory are particularly interesting topics in neuroscience that have recently been investigated. As shown in our previous study, IQGAP1, a scaffolding protein of MAPK, is involved in fear memory through interactions with GluN2A-containing NMDA receptors and the ERK1/2 cascade. However, researchers have not determined whether histone posttranslational modifications are regulated by the IQGAP1/ERK signaling pathway. We performed in vivo studies using IQGAP1-/- and IQGAP1+/+ mice to provide insights into the specific functions of IQGAP1 in memory processes and the precise mechanisms underlying its regulatory effects. IQGAP1-/- mice exhibited impaired fear memory, decreased levels of phosphorylated ERK1/2 and histone H3S10, decreased acetylation of H3K14, and decreased c-Fos expression in the hippocampus compared to IQGAP1+/+ mice after fear conditioning. HDAC2 was significantly enriched at the c-fos gene promoter in IQGAP1-/- mice. Correspondingly, the disruption of the epigenetic regulation induced by ERK1/2 signaling through an intra-hippocampal injection of the MEK antagonist U0126 or GluN2A-selective pharmacological antagonist NVP-AAM077 blocked context-dependent memory formation, while no changes were observed after treatment with the GluN2B-selective antagonist Ro25-6981. The administration of SAHA, a non-specific HDAC inhibitor, or knock-down of HDAC2 with shHDAC2-AAV in the dorsal hippocampus significantly rescued the impaired fear memory formation, H3S10 phosphorylation, H3K14 acetylation, and c-Fos expression in IQGAP1-/- mice. Thus, we postulated that the IQGAP1/ERK-dependent mechanism regulating histone posttranslational modifications via HDAC2 potentially underlies memory formation.

Photocurable Hyperbranched Polymer Medical Glue for Water-Resistant Bonding.

Medical glue represents a suitable tool to stop wound bleeding, seal wounds, bond tissues, or implant materials. However, the development of a medical glue for durable underwater bonding remains a challenge. Herein, we developed a hydrophobic hyperbranched polymer-based medical glue with water-resistant bonding ability. Specifically, the hyperbranched polythioether (HBPTE) with abundant terminal thiol groups was first prepared through a simple one-pot thiol-Michael polyaddition reaction. Due to the hyperbranched molecular structure, HBPTE is a liquid material under room temperature, thus enabling the manufacturing of a photocurable HBPTE glue by the direct addition of poly(ethylene glycol) dimethacrylate and a photoinitiator without introduction of a solvent. This solventless HBPTE glue exhibited a maximum underwater adhesive strength of 36 kPa on porcine skin compared to only <10 kPa of the commercial fibrin glue and cyanoacrylate glue. Moreover, since the hydrophobic cross-linked network resists penetration of water, the HBPTE glue minimally swelled (2-10%) and could maintain a glass sheet structure bonded together even after 2 weeks underwater. Furthermore, an in vitro cytotoxicity test showed that the HBPTE glue did not leak any cytotoxic substances and allowed for proliferation of L929 cells on its surface. Moreover, hemocompatibility tests indicated that the HBPTE glue was nonhemolytic and did not induce thrombosis. This HBPTE glue exhibited promising characteristics to potentially find use as an underwater soft tissue adhesive or sealant.