The downregulation of Tapasin in dendritic cell regulates CD8+ T cell autophagy to hamper hepatitis B viral clearance in the induced pluripotent stem cell-derived hepatocyte organoid.

Tapasin, a crucial molecular chaperone involved viral antigen processing and presentation, plays an important role in antivirus immunity. However, its impact on T cell differentiation in the context of virus clearance remains unclear. In this study, we employed induced pluripotent stem cells to differentiate into hepatocyte-like cell, which were subsequently inserted to the inverted colloidal crystal scaffolds, thus establishing a hepatocyte organoid (HO). By inoculating hepatitis B virus (HBV) particles in the system, we successfully engineered a robust in vitro HBV infection model for at least 3 weeks. Furthermore, we aimed to explore the effects of lentivirus-mediated short hairpin RNA (shRNA) targeting human Tapasin on the differentiation and antiviral function of CD8+ T cells. Specifically, we transfected dendritic cells (DCs) with Tapasin-shRNA and cocultured with T cells. The results demonstrated that Tapasin-shRNA transfected DCs effectively suppressed T cell proliferation and impeded HBV-specific cytotoxic T lymphocyte responses. Our investigation also revealed the role of mTOR pathway activation in reducing autophagy activity within CD8+ T cells. Expressions of autophagy-related proteins, beclin-1, LC3II/LC3I were decreased and PI3K/AKT/mTOR activity was increased in Tapasin-shRNA group. Collectively, our findings elucidate that shRNA targeting the Tapasin gene within DCs inhibits T cell differentiation by reducing autophagy activity to hamper viral clearance in the HBV-infected HO.

Integrative analysis and risk model construction for super­enhancer­related immune genes in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer associated with poor prognosis, and accounts for the majority of RCC-related deaths. The lack of comprehensive diagnostic and prognostic biomarkers has limited further understanding of the pathophysiology of ccRCC. Super-enhancers (SEs) are congregated enhancer clusters that have a key role in tumor processes such as epithelial-mesenchymal transition, metabolic reprogramming, immune escape and resistance to apoptosis. RCC may also be immunogenic and sensitive to immunotherapy. In the present study, an Arraystar human SE-long non-coding RNA (lncRNA) microarray was first employed to profile the differentially expressed SE-lncRNAs and mRNAs in 5 paired ccRCC and peritumoral tissues and to identify SE-related genes. The overlap of these genes with immune genes was then determined to identify SE-related immune genes. A model for predicting clinical prognosis and response to immunotherapy was built following the comprehensive analysis of a ccRCC gene expression dataset from The Cancer Genome Atlas (TCGA) database. The patients from TCGA were divided into high- and low-risk groups based on the median score derived from the risk model, and the Kaplan-Meier survival analysis showed that the low-risk group had a higher survival probability. In addition, according to the receiver operating characteristic curve analysis, the risk model had more advantages than other clinical factors in predicting the overall survival (OS) rate of patients with ccRCC. Using this model, it was demonstrated that the high-risk group had a more robust immune response. Furthermore, 61 potential drugs with half-maximal inhibitory concentration values that differed significantly between the two patient groups were screened to investigate potential drug treatment of ccRCC. In summary, the present study provided a novel index for predicting the survival probability of patients with ccRCC and may provide some insights into the mechanisms through which SE-related immune genes influence the diagnosis, prognosis and potential treatment drugs of ccRCC.

Stability and encapsulation properties of daidzein in zein/carrageenan/sodium alginate nanoparticles with ultrasound treatment.

This study aimed to prepare carrageenan/sodium alginate double-stabilized layers of zein nanoparticles loaded with daidzein using ultrasound technology to investigate the effect of ultrasound treatment on the stability of composite nanoparticles and encapsulation of daidzein. Compared with composite nanoparticles without ultrasound treatment, the encapsulation efficiency of nanoparticles was increased (90.36 %) after ultrasound treatment (320 W, 15 min). Ultrasound treatment reduced the particle size and PDI of nanoparticles and improved the stability and solubility of nanoparticles. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) revealed that the nanoparticles treated with ultrasound were smooth spherical and uniformly distributed. Fourier transform infrared spectroscopy (FTIR) results showed that the main forces that form nanoparticles are hydrogen bonding, electrostatic interactions and hydrophobic interactions. Fluorescence and CD chromatography showed that ultrasound treatment alters the secondary structure of zein and maintains nanoparticle stability. Encapsulation of daidzein in nanocarriers with ultrasound treatment can effectively scavenge DPPH and ABTS free radicals, improve antioxidant activity, and realize the slow release of daidzein in the gastrointestinal tract. The results showed that ultrasonication helps the construction of hydrophobic bioactives delivery carriers and provides better protection for unstable bioactives.

Discovery of fecal microbial signatures in patients with ankylosing spondylitis.

Objectives: This study aimed to investigate the characteristics of the gut microbiota in Chinese patients with ankylosing spondylitis (AS) and healthy controls in Quanzhou aiming to explore the correlation between microbiome changes and AS activities. Patients and methods: In this study, high-throughput sequencing of the gene of 16S ribosomal RNA (16S rRNA) in fecal samples from 40 AS patients and 40 healthy controls, for a total of 80 participants (70 males, 10 females; mean age 33.7±10.7 years; range, 15 to 58 years), was conducted between January 2018 and January 2019. Alpha and beta diversity were analyzed using the QIIME (Quantitative Insights Into Microbial Ecology) software, and differences were analyzed using Student's t-test, linear discriminant analysis coupled with effect size and Metastats. Finally, a correlation network was constructed using Pearson's analysis. Results: The alpha index values of the AS group were not significantly different from those of the control group. At the genus level, eight genera, Ruminiclostridium_9, Fusicatenibacter, Adlercreutzia, CAG-56, Intestinimonas, Lachnospira, Bacteroides, and Pseudoflavonifractor, were significantly enriched in patients with AS, whereas the abundance of uncultured_bacterium_f_Saccharimonadaceae, Prevotella_7, uncultured_bacterium_f_ Enterobacteriaceae, Cronobacter, Prevotellaceae_NK3B31_group, and Weissella were significantly decreased in patients with AS. In addition, diseaserelated gut microbial communities were detected in patients with AS. Conclusion: We found differences in the gut microbiome between the patients with AS and controls and identified potential disease activity-related bacterial communities.

Hearing Aids Combined With Educational Counseling Versus Educational Counseling Alone for Tinnitus Treatment in Patients With Hearing Loss: A Longitudinal Follow-Up Study.

PURPOSE: The effect of hearing aids (HAs) and educational counseling (EC) or their combination on tinnitus is ambiguous. This study aimed to investigate whether the combined use of HAs and EC is more effective than EC alone on tinnitus relief. METHOD: A total of 72 adults with chronic, bothersome tinnitus and coexisting sensorineural hearing loss completed at least 1-month and 3-month follow-up. After receiving EC and HA prescriptions, 21 participants selected to purchase HAs (i.e., the HA + EC group), whereas the remaining 51 refused to use HAs despite recommendations (i.e., the EC group). Tinnitus severity was measured by Tinnitus Handicap Inventory (THI), Tinnitus Evaluation Questionnaire (TEQ), and Visual Analog Scale (VAS) for loudness. The primary outcome measure was THI, and tinnitus relief was defined as a 20-point or more reduction in THI. A generalized linear mixed model was used to confirm that the heterogeneity in baseline characteristics between groups did not interfere with the results. RESULTS: The THI, TEQ, and VAS scores decreased significantly after treatments, and both groups yielded a similar trend of reduction. There were no significant differences in the incidence of tinnitus relief and time-to-event curves between the two groups. In addition, the length of follow-up did not affect treatment effectiveness. CONCLUSION: There was insufficient evidence to support the superiority of the combined use of HA and EC for tinnitus over EC with no device.

Optical transparent metasurface for dual-band Wi-Fi shielding.

An optical transparent metasurface for dual-band Wi-Fi shielding is presented in this paper. The unit cell of the proposed metasurface is composed of a hexagonal ring and a three-petal oval flower which resonate at 2.4 and 5.5 GHz, respectively. The corresponding equivalent circuit is modelled to better understand the physical phenomena of electromagnetic shielding. Based on transmission line theory and curve fitting technique, a convenient and efficient method for extracting permittivity of substrate is presented. Simulation results show that the proposed metasurface is insensitive to the polarization of incoming wave under normal incidence and offers excellent angular stability. For verifying the design, two prototypes are fabricated using different manufacturing technologies, flexible printed circuit and ink-jet printing of silver nano-particles. The measured results are in good agreement with the simulated ones. The proposed metasurface has potential applications of electromagnetic wave suppression and information security in indoor environments.

Ultrawideband and high-efficient polarization conversion metasurface based on multi-resonant element and interference theory.

In this work, an ultrawideband and high-efficient polarization conversion metasurface (PCM) is proposed, which can efficiently convert linearly polarized waves into cross-polarized waves in an ultra-wide frequency range. The unit cell of the proposed PCM is composed of two pairs of L-shaped metallic patches covered by a dielectric superstrate and an air-based substrate attached with a metallic ground. The PCM has an operating band from 3.37 to 22.07 GHz with the polarization conversion ratio (PCR) over 90% under the normal incidence, which the ratio bandwidth (fH/fL) is 6.5:1. The PCR can achieve 100% at seven resonant frequencies. The equivalent circuit model is analyzed to explain the fundamental cause of the PCM's multi-resonance and polarization conversion behaviors. In addition, all possible near-field interactions among the resonator, the superstrate, and the ground sheet can be accurately calculated using interference theory, which reveals the underlying physical mechanisms of the multi-resonance metasurface. The theoretical calculated, numerically simulated, and measured results are in good agreement. Compared to other PCMs, the proposed PCM has a simple geometry structure but an ultrawideband and high PCR property.

Enhancing the Performance of Organic Solar Cells by Prolonging the Lifetime of Photogenerated Excitons.

Exciton lifetime (τ) is crucial for the migration of excitons to donor/acceptor interfaces for subsequent charge separation in organic solar cells (OSCs); however, obvious prolongation of τ has rarely been achieved. Here, by introducing a solid additive 9-fluorenone-1-carboxylic acid (FCA) into the active layer, which comprises a nonfullerene acceptor, 3,9-bis(2-methylene-((3-(1,1-dicyanomethylene)-6/7-methyl)-indanone))-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (IT-M), τ is substantially prolonged from 491 to 928 ps, together with obvious increases in fluorescence intensity and quantum yield. Time-resolved transient infrared spectra indicate the presence of an intermolecular vibrational coupling between the electronic excited state of IT-M and the electronic ground state of FCA, which is first observed here and which can suppress the internal conversion process. IT-M-based OSCs display an improved short-circuit current and fill factor after the addition of FCA. Thus, the power conversion efficiency is increased, particularly for devices with a large donor/acceptor ratio of 1:4, whose efficiency is increased by 56%. This study describes a novel method, which is also applicable to other nonfullerene acceptors, for further improving the performance of OSCs without affecting their morphology and light absorption properties.

MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma.

PURPOSE: Moesin-ezrin-radixin-like protein (Merlin) has been identified as a tumor suppressor in several types of cancers. However, the biological function of Merlin in osteosarcoma remains unclear. MicroRNAs (miRNAs) can influence cancer progression by targeting oncogenes or anti-oncogenes. In this study, we sought to evaluate the regulation of Merlin expression by miR-25-3p and the role of the miR-25-3p/Merlin axis in osteosarcoma progression, with the aim of identifying a potential therapeutic target for osteosarcoma. MATERIALS AND METHODS: TCGA (The Cancer Genome Atlas) database was used to analyze the correlation between Merlin expression and prognosis. RT-qPCR and Western blotting analyses were performed to compare Merlin expression between normal and malignant cells. A dual-luciferase reporter assay was performed to evaluate the direct targeting of Merlin by miR-25-3p. We overexpressed miR-25-3p, or/and Merlin, in U-2 OS and 143B cells, and studied their cellular functions in vitro. MTT and colony formation assays were performed to determine the effects on cell growth. EdU and cell cycle assays were performed to analyze the effects in cell replication. We used annexin V-fluorescein isothiocyanate and propidium iodide to stain apoptotic cells, and analyzed the cells using flow cytometry. The effects on cell metastasis were studied in wound healing and transwell assays. Lastly, the underlying mechanism was determined in RT-qPCR and Western blotting experiments. RESULTS: Low Merlin expression was linked to poor prognosis. miR-25-3p was observed to directly target Merlin and downregulate its expression. miR-25-3p promoted cell growth, migration, and invasion, and inhibited apoptosis induced by cisplatin. Moreover, the overexpression of Merlin reversed the abovementioned effects of miR-25-3p. Further, the miR-25-3p/Merlin axis was observed to play an important role in the Hippo pathway, and regulated the expression of genes such as BIRC5, CTGF, and CYR61. CONCLUSION: miR-25-3p functions as an oncogenic microRNA in osteosarcoma by targeting Merlin, and may serve as a potential therapeutic target for osteosarcoma.

Combination of monoammonium glycyrrhizinate and cysteine hydrochloride ameliorated lipopolysaccharide/galactosamine-induced acute liver injury through Nrf2/ARE pathway.

Combination of monoammonium glycyrrhizinate and cysteine hydrochloride (MG-CH) has been used for treatment of chronic liver damage in clinic for several years, however, the effect of MG-CH on acute liver injury (ALI) is still obscure. In this study, we aimed to investigate the effect of MG-CH on ALI induced by co-injection of lipopolysaccharide (LPS) and d-galactosamine (GalN). Our results found that MG-CH produced the optimal therapeutic effect at the ratio of 2:1, as manifested by the increased survival percentage, decreased ALT and AST level and improved hepatic pathology. Both oxidative stress and inflammation induced by LPS/GalN were attenuated by MG-CH. Mechanism study showed that MG-CH promoted the nuclear accumulation of Nrf2 and its transcriptional activity, as well as improved Nrf2-target genes' expression. It was also found that activation of Nrf2 is dependent on the MG, not CH. Blockade of Nrf2 abolished the anti-inflammatory effect of MG-CHinduced by LPS/GalN, while inhibition of NFκB showed no effect on its anti-oxidative effect, though the inhibited phosphorylation of IκB and NFκB were detected in liver. The protective effect of MG-CH against ALI was abolished in Nrf2-/- mice. All of these results suggested that MG-CH ameliorated LPS/GalN induced ALI through Nrf2/ARE pathway.

Noncovalently fused-ring electron acceptors with near-infrared absorption for high-performance organic solar cells.

Non-fullerene fused-ring electron acceptors boost the power conversion efficiency of organic solar cells, but they suffer from high synthetic cost and low yield. Here, we show a series of low-cost noncovalently fused-ring electron acceptors, which consist of a ladder-like core locked by noncovalent sulfur-oxygen interactions and flanked by two dicyanoindanone electron-withdrawing groups. Compared with that of similar but unfused acceptor, the presence of ladder-like structure markedly broadens the absorption to the near-infrared region. In addition, the use of intramolecular noncovalent interactions avoids the tedious synthesis of covalently fused-ring structures and markedly lowers the synthetic cost. The optimized solar cells displayed an outstanding efficiency of 13.24%. More importantly, solar cells based on these acceptors demonstrate very low non-radiative energy losses. This research demonstrates that low-cost noncovalently fused-ring electron acceptors are promising to achieve high-efficiency organic solar cells.

Design, synthesis, and potent antiepileptic activity with latent nerve rehabilitation of novel γ-aminobutyric acid derivatives.

We aimed to design and synthesize novel γ-aminobutyric acid (GABA) derivatives with the combination of aspirin (ASA) of nerve rehabilitative pharmacophores so as to develop multifunctional drugs useful in the treatment of neurological disorders. Twenty-four novel esters and amides of 1a were synthesized, biologically evaluated for antiepileptic activity with the model of 4-aminopyridine (4-AP), and tested for their capacity of penetrating the blood-brain barrier (BBB) with HPLC. The distribution of 8a, ASA freed by 8a, 7c, and ASA freed by 7c within 24 h in brain tissue was measured. The structure-activity relationship (SAR) was established and the data of Computer Aided Drug Design (CADD) showed good results. With ED50 values of 0.3684-0.5199 mmol/kg, LD50 1.1487-1.3944 mmol/kg, and therapeutic index (TI) 2.65-3.15, compounds 8a, 3b, 4b, 6c, and 7c exhibited better antiepileptic activities in multiples of 0.3 to 2.2 against the control sodium valproate (VPA). Most importantly, 8a and 7c exhibited excellent antiepileptic activities with TI values of 3.15 and 3.12, respectively.