Sorbitol Destroyed Intestinal Microfold Cells (M Cells) Development through Inhibition of PDE4-Mediated RANKL Expression.

Objective: Microfold cells (M cells) are specific intestinal epithelial cells for monitoring and transcytosis of antigens, microorganisms, and pathogens in the intestine. However, the mechanism for M-cell development remained elusive. Materials and Methods: Real-time polymerase chain reaction, immunofluorescence, and western blotting were performed to analyze the effect of sorbitol-regulated M-cell differentiation in vivo and in vitro, and luciferase and chromatin Immunoprecipitation were used to reveal the mechanism through which sorbitol-modulated M-cell differentiation. Results: Herein, in comparison to the mannitol group (control group), we found that intestinal M-cell development was inhibited in response to sorbitol treatment as evidenced by impaired enteroids accompanying with decreased early differentiation marker Annexin 5, Marcksl1, Spib, sox8, and mature M-cell marker glycoprotein 2 expression, which was attributed to downregulation of receptor activator of nuclear factor kappa-В ligand (RANKL) expression in vivo and in vitro. Mechanically, in the M-cell model, sorbitol stimulation caused a significant upregulation of phosphodiesterase 4 (PDE4) phosphorylation, leading to decreased protein kinase A (PKA)/cAMP-response element binding protein (CREB) activation, which further resulted in CREB retention in cytosolic and attenuated CREB binds to RANKL promoter to inhibit RANKL expression. Interestingly, endogenous PKA interacted with CREB, and this interaction was destroyed by sorbitol stimulation. Most importantly, inhibition of PDE4 by dipyridamole could rescue the inhibitory effect of sorbitol on intestinal enteroids and M-cell differentiation and mature in vivo and in vitro. Conclusion: These findings suggested that sorbitol suppressed intestinal enteroids and M-cell differentiation and matured through PDE4-mediated RANKL expression; targeting to inhibit PDE4 was sufficient to induce M-cell development.

In silico study of androgen receptor N-terminal domain and exploration of its modulators.

The androgen receptor (AR, Uniprot: P10275) signaling plays a key role in the progression of prostate cancer, various AR-related ligands have been reported to treat prostate cancer. However, some resistance mechanisms limited the treating effect of these ligands. Since DBD binding or the allosteric binding sites in LBD of AR may allow the circumvention of some drug resistance mechanisms, anti-resistance is expected especially through the NTD (N-terminal domain) targeting. What's more, studies have shown that compounds including EPI-001 and its derivatives which bind to the Tau-5 region on NTD could be promising molecules for AR-based therapeutics. Herein, we employed aMD (accelerated molecular dynamics) simulation to fold Tau-5 unit proteins into native structure correctly. Subsequently, based on the predicted structural features of Tau-5, the virtual screening was conducted to discover new compounds targeting AR-NTD. We picked up 8 compounds (according to their docking scores and partly similar structural consists as known AR ligands) and analyzed their interaction with Tau-5, compared with the positive control EPI-001, four of the pick-up compounds showed better glide scores. Interestingly, although compound 8 had a lower docking score, it consisted of a similar component as the ligand EIQPN and the amide derivatives, this predicts that compound 8 has also the potential to be modified into an excellent AR-NTD binding molecule. These 8 compounds were all commercially available and could be tested to check whether there was a hit compound to bind the AR-NTD and to regulate its bio-activities. Together, this study described an in silico VLS approach to discover AR-NTD ligands and provided more choices for developing AR-targeted therapies.Communicated by Ramaswamy H. Sarma.

Comparison of different rhythmic auditory stimuli on prefrontal cortex cortical activation during upper limb movement in patients with Parkinson's disease: a functional near-infrared spectroscopy study.

Background: A large number of literatures show that rhythmic auditory stimulation (RAS) can effectively improve Parkinson's disease (PD) patients' gait speed, frequency and speed. Its application and curative effect on upper limb motor function is relatively few. Objective: By studying the immediate effect of RAS with different rhythms on the prefrontal cortex (PFC) blood oxygen response during upper limb movement in PD patients, this study discusses the potential neurophysiological mechanism of RAS on upper limb movement in PD patients, which is expected to provide guidance for patients with upper limb dysfunction such as Parkinson's disease. Methods: In this study, 31 PD patients with upper limb static tremors were recruited to complete the nail board task on the healthy upper limb under the baseline rhythm, slow rhythm and fast rhythm provided by the therapist. At the same time, fNIRS was used to observe the blood oxygen response of PFC. Results: There was no significant main effect onsidein all brain regions (p > 0.05), and there was no interaction between rhythm and side (p > 0.05); Except lPFC, the main effect of rhythm in other brain regions was significant (p < 0.05), and ΔHbO increased with the change of rhythm. Paired analysis showed that there were significant differences in ΔHbO between slow rhythm and baseline rhythm, between fast rhythm and baseline rhythm, and between slow rhythm and fast rhythm (p < 0.05); The ΔHbO of rPFC, lDLPFC and rDLPFC were significantly different between slow rhythm and fast rhythm (p < 0.05); there were significant differences in the ΔHbO of BA8 between slow rhythm and baseline rhythm, and between slow rhythm and fast rhythm (p < 0.05). Conclusion: RAS may be a useful upper limb rehabilitation strategy for PD patients with upper limb dysfunction. At the same time, RAS with different rhythms also have different responses to PFC blood oxygen during upper limb movement in PD patients, so that we can design interventions for this kind of cortical mechanism. Identifying the neurophysiological mechanism of RAS on upper limb movement in PD patients may help clinicians customize rehabilitation methods for patients according to clues, so as to highly personalize upper limb training and optimize its effect.

Association between autonomic dysfunction with motor and non-motor symptoms in patients with Parkinson's disease.

To investigate the association between autonomic dysfunction (AutD) and motor as well as non-motor symptoms (NMS) in patients with Parkinson's disease (PD). Fifty-three PD patients were divided into two groups based on the number of domains affected by AutD: a multi-domain AutD group (AutD-M) and a single-domain AutD group (AutD-S), as evaluated using the Scale for Outcomes in Parkinson's disease-Autonomic (SCOPA-AUT), which assesses autonomic symptoms, one of the NMS. A comprehensive comparison was conducted between the two groups, including clinical measures such as clinical scales, quantitative evaluations of motor function and exercise capacity. Spearman correlation analysis was employed to investigate the relationship between AutD severity and PD symptoms. Additionally, we performed multiple linear regression model analysis to determine whether associations between SCOPA-AUT scores and clinical assessments remained significant after adjusting for Hoehn and Yahr stage, sex, and age. PD patients in the AutD-M group exhibited significantly more severe NMS and motor symptoms compared to those in the AutD-S group. In correlation analysis, SCOPA-AUT scores showed significant correlations with multiple clinical symptoms, such as most of the NMS, 10-MWT and CPET parameters. Furthermore, regression analysis also revealed that more pronounced fatigue, anxiety, depressive symptoms, worse walking speed and impaired exercise capacity were associated with higher SCOPA-AUT scores. The presence of AutD is correlated with emotional disturbances, decreased exercise endurance, and impaired gait function in patients with PD. Early management of AutD may prove beneficial in alleviating some NMS and motor symptoms in PD.

Interferon-Gamma-Inducible Protein 16 Inhibits Hepatocellular Carcinoma via Interferon Regulatory Factor 3 on Chemosensitivity.

BACKGROUND AND AIM: Previous reports have suggested IFI16 as a tumor suppressor in hepatocellular carcinoma (HC). Nonetheless, the biological significance of IFI16 and its mechanism concerning resistance to cisplatin (DDP) in HC requires further exploration. METHODS: Samples of tumor and corresponding para-carcinoma tissues were acquired from patients with HC. Furthermore, DDP-resistant cell lines of HC, specifically HCC, Huh7 and Hepatoblastoma, HepG3, were generated by gradually increasing the concentration of DDP. Cell apoptosis and DNA damage were evaluated by utilizing flow cytometry assay and TUNEL staining. The interaction between IFI16 and interferon regulatory factor 3 (IRF3) proteins were analyzed using Co-Immunoprecipitation (Co-IP) assay. In vivo assays were conducted by establishing HC subcutaneous xenograft tumor models. RESULTS: The study found a reduction in IFI16 expression in both HC tissues and DDP-resistant HC cell lines. The binding of IFI16 to IRF3 regulated DNA damage-associated markers in vitro. Overexpression of IFI16 heightened the susceptibility of DDP-induced apoptosis and DNA damage, which was counteracted by IRF3 knockdown, while strengthened by IRF3 overexpression. Moreover, overexpression of IFI16 diminished in vivo DDP-resistant HC tumorigenicity. CONCLUSION: In summary, our findings suggest that IFI16 serves as a tumor suppressor in HC by promoting DNA damage via its interaction with IRF3, thereby reversing DDP resistance.

The novel mechanism of human norovirus induced diarrhea: Activation of PKD2 caused by HuNoVs destroyed AQP3 expression through AP2γ in intestinal epithelial cells.

Our previous work has demonstrated protein kinase D2 (PKD2) played a critical influence in experimental colitis in animal. However, the role of PKD2 in human norovirus (HuNoVs)-induced diarrhea remained unknown. Aquaporin 3 (AQP3) expression, a critical protein mediating diarrhea, was assessed by western blot, qRT-PCR in intestinal epithelial cells (IECs). Luciferase, IF, IP and ChIP assay were used to explore the mechanism through which HuNoVs regulated AQP3. Herein, we found that AQP3 expression was drastically decreased in IECs in response to VP1 transfection, the major capsid protein of HuNoVs, or HuNoVs infection. Mechanistically, HuNoVs triggered phosphorylation of PKD2 through TLR2/MyD88/IRAK4, which further inhibited AP2γ activation and nuclear translocation, leading to suppress AQP3 transactivation in IECs. Most importantly, PKD2 interacted with MyD88/IRAK4, and VP1 overexpression enhanced this complex form, which, in turn, to increase PKD2 phosphorylation. In addition, endogenous PKD2 interacted with AP2γ, and this interaction was enhanced in response to HuNoVs treatment, and subsequently resulting in AP2γ phosphorylation inhibition. Moreover, inhibition of PKD2 activation could reverse the inhibitory effect of HuNoVs on AQP3 expression. In summary, we established a novel mechanism that HuNoV inhibited AQP3 expression through TLR2/MyD88/IRAK4/PKD2 signaling pathway, targeting PKD2 activity could be a promising strategy for prevention of HuNoVs-induced gastroenteritis.

Vitronectin Destroyed Intestinal Epithelial Cell Differentiation through Activation of PDE4-Mediated Ferroptosis in Inflammatory Bowel Disease.

Objective: Vitronectin (VTN) has been reported to trigger cell pyroptosis to aggravate inflammation in our previous study. However, the function of VTN in inflammatory bowel disease (IBD) remains to be addressed. Methods: Real-time PCR and western blotting were performed to analyze VTN-regulated intestinal epithelial cell (IEC) differentiation through ferroptosis, and immunofluorescence (IF), luciferase, and chromatin immunoprecipitation were used to identify whether VTN-modulated ferroptosis is dependent on phosphodiesterase 4 (PDE4)/protein kinase A (PKA)/cyclic adenosine monophosphate-response element-binding protein (CREB) cascade pathway. In vivo experiment in mice and a pilot study in patients with IBD were used to confirm inhibition of PDE4-alleviated IECs ferroptosis, leading to cell differentiation during mucosal healing. Results: Herein, we found that caudal-related homeobox transcription factor 2-mediated IECs differentiation was impaired in response to VTN, which was attributed to enhanced ferroptosis characterized by decreased glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 expression. Inhibition of ferroptosis in IECs rescued the inhibitory effect of VTN on cell differentiation. Further analysis showed that VTN triggered phosphorylation of PDE4, leading to inhibit PKA/CREB activation and CREB nuclear translocation, which further reduced GPX4 transactivation. Endogenous PKA interacted with CREB, and this interaction was destroyed in response to VTN stimulation. What is more, overexpression of CREB in CaCO2 cells overcame the promotion of VTN on ferroptosis. Most importantly, inhibition of PDE4 by roflumilast or dipyridamole could alleviate dextran sulfate sodium-induced colitis in mice and in a pilot clinical study confirmed by IF. Conclusions: These findings demonstrated that highly expressed VTN disrupted IECs differentiation through PDE4-mediated ferroptosis in IBD, suggesting targeting PDE4 could be a promising therapeutic strategy for patients with IBD.

Bright near-infrared circularly polarized electrochemiluminescence from Au9Ag4 nanoclusters.

Metal nanoclusters are excellent electrochemiluminescent luminophores owing to their rich electrochemical and optical properties. However, the optical activity of their electrochemiluminescence (ECL) is unknown. Herein, we achieved, for the first time, the integration of optical activity and ECL, i.e., circularly polarized electrochemiluminescence (CPECL), in a pair of chiral Au9Ag4 metal nanocluster enantiomers. Chiral ligand induction and alloying were employed to endow the racemic nanoclusters with chirality and photoelectrochemical reactivity. S-Au9Ag4 and R-Au9Ag4 exhibited chirality and bright-red emission (quantum yield = 4.2%) in the ground and excited states. The enantiomers showed mirror-imaged CPECL signals at 805 nm owing to their highly intense and stable ECL emission in the presence of tripropylamine as a co-reactant. The ECL dissymmetry factor of the enantiomers at 805 nm was calculated to be ±3 × 10-3, which is comparable with that obtained from their photoluminescence. The obtained nanocluster CPECL platform shows the discrimination of chiral 2-chloropropionic acid. The integration of optical activity and ECL in metal nanoclusters provides the opportunity to achieve enantiomer discrimination and local chirality detection with high sensitivity and contrast.

Risk factors for hepatic hydrothorax in patients with cirrhosis: a clinical retrospective study.

Aims and background: Hepatic hydrothorax, which presents as an unexplained pleural effusion, is one of the important complications in patients with end-stage cirrhosis. It has a significant correlation with prognosis and mortality. The aim of this clinical study was to detect the risk factors for hepatic hydrothorax in patients with cirrhosis and to better understand potentially life-threatening complications. Methods: Retrospectively, 978 cirrhotic patients who were hospitalized at the Shandong Public Health Clinical Center from 2013 to 2021 were involved in this study. They were divided into the observation group and the control group based on the presence of hepatic hydrothorax. The epidemiological, clinical, laboratory, and radiological characteristics of the patients were collected and analyzed. ROC curves were used to evaluate the forecasting ability of the candidate model. Furthermore, 487 cases in the experimental group were divided into left, right, and bilateral groups, and the data were analyzed. Results: The patients in the observation group had a higher proportion of upper gastrointestinal bleeding (UGIB), a history of spleen surgery, and a higher model for end-stage liver disease (MELD) scores compared with the control group. The width of the portal vein (PVW) (P = 0.022), prothrombin activity (PTA) (P = 0.012), D-dimer (P = 0.010), immunoglobulin G (IgG) (P = 0.007), high-density lipoprotein cholesterol (HDL) (P = 0.022), and the MELD score were significantly associated with the occurrence of the hepatic hydrothorax. The AUC of the candidate model was 0.805 (P < 0.001, 95% CI = 0.758-0.851). Portal vein thrombosis was more common in bilateral pleural effusion compared with the left and right sides (P = 0.018). Conclusion: The occurrence of hepatic hydrothorax has a close relationship with lower HDL, PTA, and higher PVW, D-dimer, IgG, and MELD scores. Portal vein thrombosis is more common in cirrhotic patients with bilateral pleural effusion compared to those with unilateral pleural effusion.

Helicobacter pylori promotes gastric intestinal metaplasia through activation of IRF3-mediated kynurenine pathway.

BACKGROUND: Metabolic reprogramming is a critical event for cell fate and function, making it an attractive target for clinical therapy. The function of metabolic reprogramming in Helicobacter pylori (H. pylori)-infected gastric intestinal metaplasia remained to be identified. METHODS: Xanthurenic acid (XA) was measured in gastric cancer cells treated with H. pylori or H. pylori virulence factor, respectively, and qPCR and WB were performed to detect CDX2 and key metabolic enzymes expression. A subcellular fractionation approach, luciferase and ChIP combined with immunofluorescence were applied to reveal the mechanism underlying H. pylori mediated kynurenine pathway in intestinal metaplasia in vivo and in vitro. RESULTS: Herein, we, for the first time, demonstrated that H. pylori contributed to gastric intestinal metaplasia characterized by enhanced Caudal-related homeobox transcription factor-2 (CDX2) and mucin2 (MUC2) expression, which was attributed to activation of kynurenine pathway. H. pylori promoted kynurenine aminotransferase II (KAT2)-mediated kynurenine pathway of tryptophan metabolism, leading to XA production, which further induced CDX2 expression in gastric epithelial cells. Mechanically, H. pylori activated cyclic guanylate adenylate synthase (cGAS)-interferon regulatory factor 3 (IRF3) pathway in gastric epithelial cells, leading to enhance IRF3 nuclear translocation and the binding of IRF3 to KAT2 promoter. Inhibition of KAT2 could significantly reverse the effect of H. pylori on CDX2 expression. Also, the rescue phenomenon was observed in gastric epithelial cells treated with H. pylori after IRF3 inhibition in vitro and in vivo. Most importantly, phospho-IRF3 was confirmed to be a clinical positive relationship with CDX2. CONCLUSION: These finding suggested H. pylori contributed to gastric intestinal metaplasia through KAT2-mediated kynurenine pathway of tryptophan metabolism via cGAS-IRF3 signaling, targeting the kynurenine pathway could be a promising strategy to prevent gastric intestinal metaplasia caused by H. pylori infection. Video Abstract.

Evaluation of changes in M. aeruginosa growth and microcystin production under phosphorus starvation via transcriptomic surveys.

Phosphorus (P) is an important nutrient for the growth and metabolism of algae. Although P typically limits the growth of algae, little is known regarding the molecular response of Microcystis aeruginosa under P starvation. The transcriptomic and physiological responses of Microcystis aeruginosa to P starvation were investigated in this study. P starvation affected the growth, photosynthesis, and Microcystin (MC) production of Microcystis aeruginosa and triggered cellular P-stress responses for 7 days. In terms of physiology, P starvation inhibited the growth and MC production, while the slight promotion of photosynthesis in Microcystis aeruginosa compared to P-replete. For transcriptome, the down-regulation of genes related to MC production controlled by mcy genes and ribosome metabolism (17 genes encoding ribosomal proteins) was observed while transport genes (sphX and pstSAC) were significantly upregulated. In addition, some other genes are related to photosynthesis and the use of other forms of P displayed increases or decreases in transcripts abundance. These results suggested that the limitation of P had a diverse performance on aspects of growth and metabolism in M. aeruginosa and obviously enhanced the ability to adapt to the P stress environment. They provide a comprehensive understanding of the P physiology of Microcystis aeruginosa and theoretical support for eutrophication.

Transforming Silver Nanoclusters from Racemic to Homochiral via Seeded Crystallization.

Chirality has risen as an attractive topic in materials research in recent years, but the attainment of enantiopure materials remains a major challenge. Herein, we obtained homochiral nanoclusters by a recrystallization strategy, without any chiral factors (i.e., chiral ligands, counterions, etc.). Through the rapid flipping of configuration of silver nanoclusters in solution, the initial racemic Ag40 (triclinic) nanoclusters are converted to homochiral (orthorhombic) as revealed by X-ray crystallography. In the seeded crystallization, one homochiral Ag40 crystal is used as a seed to direct the growth of crystals with specific chirality. Furthermore, enantiopure Ag40 nanoclusters can be used as amplifiers for the detection of chiral carboxylic drugs. This work not only provides chiral conversion and amplification strategies to obtain homochiral nanoclusters but also explains the chirality origin of nanoclusters at the molecular level.

Injectable self-assembled dual-crosslinked alginate/recombinant collagen-based hydrogel for endometrium regeneration.

The disadvantages of mainstream therapies for endometrial injury are difficult to resolve, herein, we suggest an omnibearing improvement strategy by introducing an injectable multifunctional self-assembled dual-crosslinked sodium alginate/recombinant collagen hydrogel. The hydrogel possessed a reversible and dynamic double network based on dynamic covalent bonds and ionic interactions, which also contributed to excellent capability in viscosity and injectability. Moreover, it was also biodegradable with a suitable speed, giving off active ingredients during the degradation process and eventually disappearing completely. In vitro tests exhibited that the hydrogel was biocompatible and able to enhance endometrial stromal cells viability. These features synergistically promoted cell multiplication and maintenance of endometrial hormone homeostasis, which accelerated endometrial matrix regeneration and structural reconstruction after severe injury in vivo. Furthermore, we explored the interrelation between the hydrogel characteristics, endometrial structure, and postoperative uterine recovery, which would benefit deep research on regulation of uterine repair mechanism and optimization of hydrogel materials. The injectable hydrogel could achieve favourable therapeutic efficacy without the need of exogenous hormones or cells, which would be of clinical value in endometrium regeneration.

Nanovaccine that activates the NLRP3 inflammasome enhances tumor specific activation of anti-cancer immunity.

Neoantigen cancer vaccines that target tumor specific mutations are emerging as a promising modality for cancer immunotherapy. To date, various approaches have been adopted to enhance efficacy of these therapies, but the low immunogenicity of neoantigens has hindered clinical application. To address this challenge, we developed a polymeric nanovaccine platform that activates the NLRP3 inflammasome, a key immunological signaling pathway in pathogen recognition and clearance. The nanovaccine is comprised of a poly (orthoester) scaffold engrafted with a small-molecule TLR7/8 agonist and an endosomal escape peptide that facilitates lysosomal rupture and NLRP3 inflammasome activation. Upon solvent transfer, the polymer self-assembles with neoantigens to form ∼50 nm nanoparticles that facilitate co-delivery to antigen-presenting cells. This polymeric activator of the inflammasome (PAI) was found to induce potent antigen-specific CD8+ T cell responses characterized by IFN-γ and GranzymeB secretion. Moreover, in combination with immune checkpoint blockade therapy, the nanovaccine stimulated robust anti-tumor immune responses against established tumors in EG.7-OVA, B16·F10, and CT-26 models. Results from our studies indicate that NLRP3 inflammasome activating nanovaccines demonstrate promise for development as a robust platform to enhance immunogenicity of neoantigen therapies.

Aldehyde-mediated adaptive membranes with self-healing and antimicrobial properties for endometrial repair.

Traditional treatment methods for irreversible endometrial damage face a number of challenges in clinical practice, the most important of which are bacterial infection and the inability to restore endometrial function. By modifying glucan, oxidized dextran (OD) with multifunctional aldehyde groups was obtained in this study. Based on the dynamic Schiff base reaction between gelatin (GA) and OD, a GA-OD adaptive membrane with good biocompatibility, self-healing, biodegradability, and antimicrobial properties was created. In vitro studies revealed that GA and OD cross-linking overcame GA's low gel temperature, accelerated gelling, and improved mechanical properties, hydrophilicity, and degradability. The dynamic bond formed by the reaction between GA and OD caused the GA-OD film to self-heal. Meanwhile, the GA-OD membrane had antibacterial properties. To assess the repair effect of GA-OD film, an in vivo rat endometrial injury model filled with GA-OD adaptive membrane was created. According to the results of the study, the GA-OD membrane was biocompatible, and the uterine tissue did not have edema and inflammation. Further study on the postoperative endometrial regeneration effect of GA-OD material showed that it had an excellent ability for epithelial reconstruction and cell proliferation. As a result, the use of GA-OD composite film in endometrial repair has promising therapeutic implications.

Versatile Superatom Complex Nanocluster for the Construction of Framework Materials.

Accurately controlling the assembly of nanometer-sized building blocks presents an important but significant challenge for the construction of functional framework materials, which requires the development of highly stable versatile nanosized assembly modules with multiple coordination sites. In this study, [Ag23(SAdm)12]3+ (Ag23, in which SAdm = 1-adamantanethiol, i.e., C10H15S), a chiral superatom complex nanocluster, was synthesized and assembled into various topologies. We constructed two kinds of framework materials, i.e., superatom complex inorganic framework (SCIF) and superatom complex organic framework (SCOF) materials, including [Ag23(SAdm)12](SbF6)2X (Ag23-1; X = Cl-/SbF6-, a SCIF), [Ag23(SAdm)12](SbF6)3 (Ag23-2, a SCIF), [Ag23(SAdm)12](SbF6)3(bpy)3 (Ag23-bpy, a SCOF, in which bpy = 4,4'-bipyridine, i.e., C10H8N2), and [Ag23(SAdm)12](SbF6)3(dpbz)3 (Ag23-dpbz, a SCOF, in which dpbz = 1,4-bis(4-pyridyl)benzene, i.e., C16H12N2), owing to strong interactions between the versatile Ag23 and the inorganic and organic linkers. Ag23-1, Ag23-2, and Ag23-bpy exhibit two superstructures with interpenetrating frameworks and adamantane-like, hexagonal, and cubic topologies, while Ag23-dpbz displays three superstructures with interpenetrating frameworks and cubic topologies. Ag23-dpbz exhibits the largest specific surface area as well as the strongest photoluminescence and electrochemiluminescence signals owing to its dense network arrangement. This work contributes to the construction of nanocluster-based framework materials and helps to elucidate the effect of the assembly mode on the material properties and functionalities.

Neural Processing Differences of Facial Emotions Between Human and Vehicles: Evidence From an Event-Related Potential Study.

Vehicle "faces" are a crucial factor influencing consumer intention to purchase gasoline and electric vehicles. However, little empirical evidence has demonstrated whether people process a vehicle's face similarly to a human's face. We investigated the neural processing relationship among human facial emotions and facial emotions of gasoline and electric vehicles using a 2 (emotional) × 3 (face type) repeated measures design and electroencephalograph (EEG) recordings. The results showed that human faces appear to share a partly similar neural processing mechanism in the latency of 100-300 ms, and that both human and vehicle faces elicited the ERP components N170, EPN, and P2. The large EPN and P2 suggest that gasoline vehicle facial emotions can be perceived more efficiently than those of electric vehicles. These findings provide an insight for vehicle designers to better understand the facial emotions presented by cars.

Cirsiliol mitigates Aß fibrillation and underlying membrane-leakage associated neurotoxicity: A possible implication in the treatment of neurodegenerative disease.

Protein aggregating is known as a leading pathogenic characteristic of a wide range of neurodegenerative diseases (NDs). Preventing amyloid-ß (Aß) aggregation and uncovering the associated mechanism through the application of small bioactive compounds can be considered as a useful strategy in hampering the onset of ND. In this study, we analyzed the inhibitory effects of cirsiliol, a trihydroxy-dimethoxyflavone, against human Αß42 fibrillization. Also, we explored the probable neurotoxicity of Αß42 oligomers grown with cirsiliol at different molar ratios on PC-12 cells after 24 h. The results showed that significant changes in ThT and ANS fluorescence intensities, Congo red absorbance, and ellipticity changes were modulated by co-incubation of cirsiliol with Αß42, in a concentration-dependent manner. The spectroscopy outcomes were also supported by imaging analysis, where a few Αß42 fibrillar conformations were detected with cirsiliol. In addition, cellular assays demonstrated that co-incubated Αß42 samples with cirsiliol regulated the cell mortality, LDH release, and caspase-3 activation relative to the PC-12 exposed to Aß42 oligomers alone. In conclusion, it can suggest that cirsiliol can be used as a potential candidate in the development of small molecules-based drugs for the advancement of therapeutic platforms against ND.

An overview on the exploring the interaction of inorganic nanoparticles with microtubules for the advancement of cancer therapeutics.

Targeting microtubules (MTs), dynamic and stable proteins in cells, by different ligands have been reported to be a potential strategy to combat cancer cells. Inorganic nanoparticles (NPs) have been widely used as anticancer, antibacterial and free radical scavenging agents, where they come in contact with biological macromolecules. The interaction between the NPs and biological macromolecules like MTs frequently occurs through different mechanisms. A prerequisite for a detailed exploration of MT structures and functions for biomedical applications like cancer therapy is to investigate profoundly the mechanisms involved in MT-NP interactions, for which the full explanation and characterization of the parameters that are responsible for the formation of a NP-protein complex are crucial. Therefore, in view of the fact that the goal of the rational NP-based future drug design and new therapies is to rely on the information of the structural details and protein-NPs binding mechanisms to manipulate the process of developing new potential drugs, a comprehensive investigation of the essence of the molecular recognition/interaction is also of considerable importance. In the present review, first, the microtubule (MT) structure and its binding sites upon interaction with MT stabilizing agents (MSAs) and MT destabilizing agents (MDAs) are introduced and rationalized. Next, MT targeting in cancer therapy and interaction of NPs with MTs are discussed. Furthermore, interaction of NPs with proteins and the manipulation of protein corona (PC), experimental techniques and direct interaction of NPs with MTs, are discussed, and finally the challenges and future perspective of the field are introduced. We envision this review can provide useful information on the manipulation of the MT lattice for the progress of cancer nanomedicine.

IFI16 induces inflammation in hepatitis B virus-associated glomerulonephritis by regulating the Caspase-1/ IL-1 ß pathway.

AIMS AND BACKGROUND: IFI16 plays an important role in innate immunity against invasive microbial infection by sensing double-stranded DNA viruses due to caspase-1-dependent inflammasome activation and subsequent maturation and secretion of IL-1ß. However, the role of IFI16 in regulating the immune response to viruses in Hepatitis B Virus-Associated Glomerulonephritis (HBV-GN), especially in sensing hepatitis B virus (HBV), has not been determined. In this study, we investigated the inflammatory role of IFI16 in HBV-GN. METHODS: A total 75 kidney tissue including 50 HBV-GN and 25 chronic glomerulonephritis (CCN) were collected to determine the expression of IFI16, Caspase-1 and IL-1ß using immunohistochemistry (IHC), then the correlation between them was analyzed. In vitro, the primary human glomerular mesangial (HGM) cells and HEK-293 T cell lines were used in this study. The cell lines were both co-transfected with HBVDNA and overexpression or silencing IFI16. Quantitative Real-time PCR and western blotting were used to determine the expression of IFI16, Caspase-1 and IL-1ß. RESULTS: IFI16 expression in HBV-GN biopsies (80.0%) was significantly higher than in CGN (24.0%) and positively correlated with HBVDNA,caspase-1 and IL-1ß expression in HBV-GN. Meanwhile, over expression of IFI16 increased caspase-1 and IL-1ß expression in HBV-infected HGM and HEK-293 T cell lines, knockdown of IFI16 mRNA by siRNA resulted in downregulation of the caspase-1 and IL-1ß expression in both cell lines. CONCLUSIONS: The elevation of IFI16 during HBV infection or replication may contribute to renal damage due to inflammation, thus providing a putative therapeutic target and a new avenue for researching the pathogenesis of HBV-GN.