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Objectives: Varicella-zoster virus (VZV) can induce herpes zoster (HZ) and postherpetic neuralgia (PHN). Immune cells play an important role in regulating HZ and PHN pathogenesis, but the dynamic immune profiles and molecular mechanisms remain unclear. This study aimed to screen dynamic immune signatures during HZ progression and elucidate the mechanism of VZV-specific T cells in PHN. Methods: We used cytometry by time-of-flight (CyTOF) to analyze peripheral blood mononuclear cells (PBMC) samples from 45 patients with HZ and eight age-sex-matched healthy controls, eight PHN samples and seven non-PHN samples. Correlations between the immune subsets and clinical pain-related scores were performed. Further, the characteristics of VZV-specific T cells between PHN and non-PHN patients were evaluated by VZV peptide pools stimulation. The expression level of cytokines, including granzyme B, interleukin (IL)-2, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α was performed via cytometric bead array. Finally, we analyzed the alteration of Ca2+ signals in dorsal root ganglion (DRG)-derived cells after TNF-α stimulation. Results: We investigated the dynamic characteristics of the immune landscape of peripheral blood samples of patients with HZ and PHN, and depicted two major dynamic signatures in NK, CD4+ and CD8+ T subsets in patients with HZ, which closely correlated with clinical pain-related scores. The frequency of PD-1+CD4+ T cells, VZV-specific PD-1+CD4+ T cells, and the amount of TNF-α produced by VZV-specific T cells were higher in patients with PHN than without PHN. Furthermore, we showed that TNF-α could induce calcium influx in DRG-derived cells in a dose-dependent manner. Conclusions: Our results profiled the dynamic signatures of immune cells in patients with HZ and highlighted the important role of VZV-specific T cells in the pathogenesis of PHN. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is a positive-sense, single-stranded RNA virus responsible for the COVID-19 pandemic. It remains unclear whether and to what extent the virus in human host cells undergoes RNA editing, a major RNA modification mechanism. Here we perform a robust bioinformatic analysis of metatranscriptomic data from multiple bronchoalveolar lavage fluid samples of COVID-19 patients, revealing an appreciable number of A-to-I RNA editing candidate sites in SARS-CoV-2. We confirm the enrichment of A-to-I RNA editing signals at these candidate sites through evaluating four characteristics specific to RNA editing: the inferred RNA editing sites exhibit (i) stronger ADAR1 binding affinity predicted by a deep-learning model built from ADAR1 CLIP-seq data, (ii) decreased editing levels in ADAR1-inhibited human lung cells, (iii) local clustering patterns, and (iv) higher RNA secondary structure propensity. Our results have critical implications in understanding the evolution of SARS-CoV-2 as well as in COVID-19 research, such as phylogenetic analysis and vaccine development. Author summary: The COVID-19 pandemic is caused by SARS-CoV-2, an RNA virus. In the cells of COVID-19 patients, SARS-CoV-2 interacts with human proteins and is potentially subjected to their enzymatic activities. Here we investigated whether human protein enzymes can change the nucleotide sequence of SARS-CoV-2, thereby leaving a unique molecular footprint. We developed a robust computational algorithm to analyze the sequence data of SARS-CoV-2 obtained from lung fluid samples of COVID-19 patients and found that the virus contains new nucleotide changes that are likely induced by ADAR1, a powerful human protein that can modify specific nucleotide positions in many human transcripts. We further confirmed that the characteristics of the nucleotide changes detected in SARS-CoV-2 are similar to those observed in the human genes. Thus, these ADAR1-induced nucleotide changes may represent an under-appreciated force that can affect the evolution of SARS-CoV-2. Our study helps researchers better understand the evolutionary trajectory of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

This paper investigates the joint effects of in-phase and quadrature-phase imbalance (IQI) and imperfect successive interference cancellation (ipSIC) on the cooperative Internet of Things (IoT) nonorthogonal multiple access (NOMA) networks where the Nakagami-m fading channel is taken into account. The closed-form expressions of outage probability for the far and near IoT devices are derived to evaluate the outage behaviors. For deeper insights of the performance of the considered system, the approximate outage probability and diversity order in high signal-to-noise ratio (SNR) regime are obtained. In addition, we also analyze the throughput and energy efficiency to characterize the performance of the considered system. The simulation results demonstrate that, compared with IQI, ipSIC has a greater impact on the outage performance for the near-IoT-device of the considered system. Furthermore, we also find that the outage probabilities of IoT devices can be minimized by selecting a specific power allocation scheme. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (OA) pain is the most common joint pain. Currently, dysfunction in the central nervous system rather than knee joint degeneration is considered to be the major cause of chronic knee OA pain; however, the underlying mechanism remains unknown. The aim of this study was to explore whether spinal NF-κB plays a critical role in chronic knee OA pain. In this study, we used a model induced by the intra-articular injection of monosodium iodoacetate. Spinal NF-κB and the phosphorylation and activation status of NF-κB p65/RelA (p-p65) were inhibited by the intrathecal injection of the inhibitor pyrrolidine dithiocarbamate in this model. After behavioral assessment, the knee was dissected for histopathology, and the spinal cord was dissected and examined for NF-κB, p-p65, and cytokine expression. Furthermore, the quantity and activity of neurons, astrocytes, and microglial cells and their colocalization with p-p65 in the spinal dorsal horn were investigated. Our findings included the following: (1) histology, the pathological changes in the joints of the knee OA model were basically consistent with knee OA patients; (2) the protein and transcription levels of NF-κB/p65 and p-p65 increased before day 14, appeared to decrease on day 21 and increased again on day 28, and the tendency of weight bearing was similar; (3) on days 21 and 28, the intrathecal injection of pyrrolidine dithiocarbamate markedly prevented the monosodium iodoacetate-induced reduction in the paw withdrawal threshold; (4) real-time polymerase chain reaction demonstrated that the expression of TNF-α and IL-33 was suppressed in the knee OA model by the intrathecal injection of pyrrolidine dithiocarbamate; and (5) immunofluorescence revealed that astrocytes were activated and that p-p65 was mainly increased in astrocytes. Our findings indicate that the spinal NF-κB/p65 pathway in astrocytes modulates neuroimmunity in rat model of intra-articular monosodium iodoacetate-induced advanced OA. [ABSTRACT FROM AUTHOR]

A distyryl boron dipyrromethene based photosensitiser substituted with 1,2,4,5-tetrazine and alkyne moieties was prepared. Through site-specific bioorthogonal reactions with the complementary functional tags anchored on the membrane of A431 human epidermoid carcinoma cells, this versatile photosensitiser exhibited enhanced cellular uptake and photocytotoxicity. The bioorthogonal ligation was also demonstrated in tumour-bearing nude mice. [ABSTRACT FROM AUTHOR]

Brassica napus is an important oilseed crop worldwide. Although seed weight is the main determinant of seed yield, few studies have focused on the molecular mechanisms that regulate seed weight in B. napus. In this study, the immature seeds of G-42 and 7–9, two B. napus doubled haploid (DH) lines with extremely different thousand-seed weight (TSW), were selected for a transcriptome analysis to determine the regulatory mechanisms underlying seed weight at the whole gene expression level and to identify candidate genes related to seed weight. A total of 2,251 new genes and 2,205 differentially expressed genes (DEGs) were obtained via RNA-seq (RNA sequencing). Among these genes, 1,747 (77.61%) new genes and 2020 (91.61%) DEGs were successfully annotated. Of these DEGs, 1,118 were up-regulated and 1,087 were down-regulated in the large-seed line. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database analysis indicated that 15 DEGs were involved in ubiquitin-mediated proteolysis and proteasome pathways, which might participate in regulating seed weight. The Gene Ontology (GO) database indicated that 222 DEGs were associated with the biological process or molecular function categories related to seed weight, such as cell division, cell size and cell cycle regulation, seed development, nutrient reservoir activity, and proteasome-mediated ubiquitin-dependent protein catabolic processes. Moreover, 50 DEGs encoding key enzymes or proteins were identified that likely participate in regulating seed weight. A DEG (GSBRNA2T00037121001) identified by the transcriptome analysis was also previously identified in a quantitative trait locus (QTL) region for seed weight via SLAF-seq (Specific Locus Amplified Fragment sequencing). Finally, the expression of 10 DEGs with putative roles in seed weight and the expression of the DEG GSBRNA2T00037121001 were confirmed by a quantitative real-time reverse transcription PCR (qRT-PCR) analysis, and the results were consistent with the RNA sequencing data. This work has provided new insights on the molecular mechanisms underlying seed weight-related biosynthesis and has laid a solid foundation for further improvements to the seed yield of oil crops. [ABSTRACT FROM AUTHOR]

ABSTRACT Simultaneously reinforced and toughened PPO/HIPS/SEBS/glass fiber (GF) 60/40/5/30 composites were successfully prepared with GF as reinforcing agent and SEBS as toughener. The formulation of PPO/HIPS/SEBS/GF quaternary composites was stepwise optimized by evaluating the effect of GF and SEBS on the processing, mechanical and thermal properties of the composites. The synergistic effects of GF reinforcement and elastomer toughening are attributed to high performance PPO/HIPS/SEBS/GF composites. Among the four elastomers studied, SEBS exhibited as effective toughener for PPO/HIPS matrix and the resulted PPO/HIPS/SEBS/GF composites presented a good combination of mechanical and thermal properties. The optimized PPO/HIPS/SEBS/GF 60/40/5/30 quaternary composites displayed a tensile strength of 123.6 MPa, a bending strength of 149.7 MPa, an unnotched impact strength of 46.6 KJ/m2 and a heat distortion temperature of 148.9°C. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40299. [ABSTRACT FROM AUTHOR]

In this paper, a dual cylindrical metallic grating-cladding polymer hollow terahertz waveguide is proposed for the transmission of a wavelength range between 100 μm and 1.5 mm with low loss. The waveguide is comprised of copper cylindrical gratings embedded in both sides of hollow high-density polyethylene tubing. Numerical calculation shows that the dual cylindrical metallic grating-cladding polymer hollow waveguide can guide terahertz waves in the central air core with excellent mode qualities, and experimental results confirm that the attenuation constant of linear polarization HE11 mode can be reduced to 0.62 dB/m. [ABSTRACT FROM AUTHOR]

Epigenetic reader proteins interpret histone epigenetic marks to regulate gene expression. Given their vital roles and the link between their dysfunction and various diseases, these proteins present compelling targets for therapeutic interventions. Nevertheless, designing selective inhibitors for these proteins poses significant challenges, primarily due to their unique properties such as shallow binding sites and similarities with homologous proteins. To overcome these challenges, we propose an innovative strategy that uses phage display with a genetically encoded noncanonical amino acid (ncAA) containing an epigenetic mark. This ncAA guides binding to the reader protein's active site, allowing the identification of peptide inhibitors with enhanced affinity and selectivity. In this study, we demonstrate this novel approach's effectiveness by identifying potent inhibitors for the ENL YEATS domain that plays a critical role in leukemogenesis. Our strategy involved genetically incorporating N ε -butyryl-l-lysine (BuK), known for its binding to ENL YEATS, into a phage display library for enriching the pool of potent inhibitors. One resultant hit was further optimized by substituting BuK with other pharmacophores to exploit a unique π-π-π stacking interaction with ENL YEATS. This led to the creation of selective ENL YEATS inhibitors with a K D value of 2.0 nM and a selectivity 28 times higher for ENL YEATS than its close homologue AF9 YEATS. One such inhibitor, tENL-S1f, demonstrated robust cellular target engagement and on-target effects to inhibit leukemia cell growth and suppress the expression of ENL target genes. As a pioneering study, this work opens up extensive avenues for the development of potent and selective peptidyl inhibitors for a broad spectrum of epigenetic reader proteins., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Background: The 8-item Morisky Medication Adherence Scale (MMAS-8) is a simple, economic and easy tool to evaluate the medication compliance of chronic disease. The reliability and validity of the MMAS-8 in patients with chronic pain were unclear. Therefore, we aimed to validate the MMAS-8 for detecting nonadherent patients with chronic pain., Methods: A modified MMAS-8 was used to assess the medication compliance of patients with chronic pain who were treated at our hospital from July 2018 to October 2018. Cronbach's α was used to evaluate the internal consistency, and a factor analysis was used to examine the construct validity. Convergent validity was assessed by comparing the MMAS-8 and a medication adherence visual analog score (MA-VAS) through Pearson's correlation coefficient., Results: A total of 113 patients were evaluated. The (t-test) results revealed that there was a significant difference in average scores between the low-score group (who scored less than 5 points) and the high-score group (who scored 8 points or above), indicating that the scale displayed a good degree of discrimination. Except for Items 4 and 5, all the other items exhibited a good correlation with the total score (correlation coefficient >0.5; P<0.05). The Cronbach's α coefficient was 0.625, indicating that the scale's internal consistency was relatively satisfactory. Two common factors, which explained 62.978% of the total variance, were extracted by factor analysis to examine the construct validity of the MMAS-8, and the load of the 6 items was greater than 0.4. The Pearson correlation coefficient was 0.845 (P<0.001); thus, convergent validity was high., Conclusions: The modified MMAS-8 exhibited acceptable reliability and validity in evaluating medication compliance in patients with chronic pain; thus, it can be applied to detect nonadherent patients with chronic pain.