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Background and Objectives: The kidney is a primary target for the accumulation of particulate matter (PM2.5). This study aimed to investigate PM2.5-induced renal toxicity mechanisms, focusing on the aryl hydrocarbon receptor (AhR)-Hsp90-MDM2 axis and its impact on vitamin D receptor (VDR) ubiquitination., Methods: PM2.5's role in activating the AhR and its downstream pathways was investigated using in vitro and in vivo models. Renal damage and therapeutic effects in PM2.5-exposed and paricalcitol-treated mice were evaluated using weight measurements, histopathology, and scanning electron microscopy. AhR, Hsp90, and VDR localization and expression in renal cells were assessed using FISH and western blot. Protein interactions were examined using co-immunoprecipitation. Differentially expressed gene (DEG) analysis of GEO datasets was used to identify related proteins and genes., Results: PM2.5 exposure caused significant renal damage in mice, including increased serum creatinine, albuminuria, and histopathological deterioration, which were alleviated by paricalcitol. PM2.5 induced the nuclear translocation of AhR and Hsp90 and reduced nuclear VDR expression; paricalcitol reversed these effects. Immunohistochemistry confirmed these findings. PM2.5 upregulated the NLRP3/caspase-1/IL-1β/IL-18 axis, which was reversed by paricalcitol treatment. Inhibition of Hsp90 increased nuclear VDR expression through MDM2 mediation. DEG analysis identified VDR-regulated genes; PM2.5 increased the mRNA levels of IL-6, IL-2, and CXCL8, which were downregulated by Hsp90 and MDM2 inhibitors, with VDR agonists further decreasing these levels., Conclusion: This study reveals a novel mechanism of PM2.5-induced renal toxicity through the AhR-Hsp90-MDM2 axis, promoting VDR ubiquitination and degradation and increasing inflammation. These findings provide a foundation for future studies and lay the groundwork for developing targeted interventions to mitigate the public health impact of PM2.5 exposure., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☐ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024. Published by Elsevier Inc.)

This study aimed to investigate the effect and potential mechanism of evodiamine (EVO) on proliferation and apoptosis of nasopharyngeal carcinoma (NPC) cells. EVO inhibited proliferation, blocked cell cycle progression, and induced apoptosis of NPC cells. There are 27 known anti-NPC targets of EVO, of which eight are core targets, namely SRC, ERBB2, STAT3, MAPK8, NOS3, CXCL8, APP, and HDAC1. Molecular docking analysis showed that the binding of EVO with its key targets (SRC, ERBB2) was good. EVO also reduced the expression of SRC and ERBB2, the key proteins p-MEK and p-ERK1/2 of the MAPK/ERK signaling pathway, and the downstream proteins PCNA and XIAP. EVO inhibited the growth of NPC xenografts in nude mice and reduced the expression levels of SRC, ERBB2, ERK1/2, p-ERK1/2, PCNA and XIAP in NPC tissue. When the MAPK/ERK signaling pathway was activated by epidermal growth factor (EGF), the expression levels of PCNA and XIAP increased, the cell proliferation index increased, and the apoptosis rate decreased in the EGF + EVO treatment group compared to treatment with EVO alone. These changes indicated that the inhibitory effect of EVO on proliferation and apoptosis of NPC cells was related to the down-regulation of SRC and ERBB2 expression, and further inhibition of the MAPK/ERK signaling pathway., (© 2024. The Author(s).)

Ca 2+ -binding proteins (CaBPs; CaBP1-5) are a subfamily of neuronal Ca 2+ sensors with high homology to calmodulin. Notably, CaBP4, which is exclusively expressed in rod and cone photoreceptors, is crucial for maintaining normal retinal functions. However, the functional roles of CaBP1, CaBP2, and CaBP5 in the retina remain elusive, primarily due to limited understanding of their expression patterns within inner retinal neurons. In this study, we conducted a comprehensive transcript analysis using single-cell RNA sequencing datasets to investigate the gene expression profiles of CaBPs in mouse and human retinal neurons. Our findings revealed notable similarities in the overall expression patterns of CaBPs across both species. Specifically, nearly all amacrine cell, ganglion cell, and horizontal cell types exclusively expressed CaBP1. In contrast, the majority of bipolar cell types, including rod bipolar (RB) cells, expressed distinct combinations of CaBP1, CaBP2, and CaBP5, rather than a single CaBP as previously hypothesized. Remarkably, mouse rods and human cones exclusively expressed CaBP4, whereas mouse cones and human rods coexpressed both CaBP4 and CaBP5. Our single-cell reverse transcription polymerase chain reaction analysis confirmed the coexpression CaBP1 and CaBP5 in individual RBs from mice of either sex. Additionally, all three splice variants of CaBP1, primarily L-CaBP1, were detected in mouse RBs. Taken together, our study offers a comprehensive overview of the distribution of CaBPs in mouse and human retinal neurons, providing valuable insights into their roles in visual functions., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Liu et al.)

Background: The association between Estradiol (E2) levels and abdominal aortic calcification (AAC) in postmenopausal women remains unclear., Methods: 614 postmenopausal women from the 2013-2014 NHANES survey cycle were included in this study. The study population was divided into 3 groups according to E2 tertiles: Tertile1 (2.12-3.57pg/mL), Tertile2 (3.60-7.04pg/mL), and Tertile3 (7.06-38.4pg/mL). Estrogen concentration data were natural logarithmically transformed. A Kauppila score > 5 was regarded as prominent arterial calcification and was used to define (EAAC). Logistic regression models were used to assess the association between E2 levels and EAAC prevalence. Subgroup analyses were performed to test whether the association between E2 levels and EAAC prevalence was consistent in different groups. Sensitivity analyses tested the stability of the model in women older than 45 years., Results: EAAC prevalence was significantly higher in Tertile1 (16.6%) than in Tertile2 (9.8%) and Tertile3 (8.3%). On a continuous scale, the adjusted model showed a 58% [OR (95%CI), 1.58 (1.02, 2.54)] increase in the risk of EAAC prevalence for per unit decrease in ln(E2). On a categorical scale, the adjusted model showed that Tertile1 and Tertile2 were 2.55 [OR (95%CI), 2.55 (1.10, 5.92)] and 1.31[OR (95%CI), 1.31(1.03, 2.57)] times higher risk of suffering from EAAC than Tertile3, respectively., Conclusion: This study found that a higher prevalence of AAC in postmenopausal women is closely associated with lower serum E2 levels. Our research further underscores the importance of E2 in maintaining cardiovascular health in postmenopausal women and suggests that monitoring E2 levels may aid in the early prevention and management of AAC and related cardiovascular diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Li, Shen and He.)

The increasing discharge of oily wastewater from life poses a serious threat to the ecological environment and human health. To develop green, efficient, and low-cost materials for oil-water separation, a superhydrophobic photothermal oil-absorbing sponge (CAC-PDA@MF) was prepared by using nanoscale coconut shell activated carbon (CAC) loaded on a melamine sponge in this study. The sponge had excellent superhydrophobicity (WCA of 159.53°) due to the reduction of surface energy by grafting long-chain silanes. The adsorption capacity of the sponge was 69.04 g/g-158.27 g/g for a wide range of oils and organic solvents, and the sponge had excellent mechanical properties for multiple adsorption and recovery of oil. After 50 cycles of oil-water separation, its separation efficiency was maintained at over 98 %. In addition, the material had high acid, alkali, and salt resistance as well as excellent photothermal conversion properties. Its surface temperature rose rapidly to 100 °C and above, at a light intensity of 1.0 kW/m 2 . The material was capable of adsorbing and recovering high-viscosity oils that were solid or semi-solid at room temperature. Its versatility and commercial value made it a promising candidate for a wide range of applications., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

T follicular helper cells (Tfh) were initially identified nearly two decades ago as critically important in directing B-cell maturation and antibody generation in the germinal centers of secondary lymphoid tissues. Since then, Tfh cells have become the center of sustained investigation in oncology due to their unique, often paradoxical roles in tumour immunity. Specifically, Tfh cells in the tumour microenvironment can enhance anti-tumour immune response or promote, through the same mechanisms, tumour progression. These dual roles largely result from Tfh cells controlling unique cytokine secretions and, in turn, shifting the net effect of the Tfh-driven immune response (by directly and indirectly affecting the activities of other cytotoxic T cells and natural killer cells). The dual nature of the Tfh is the basis for our commentary, which highlights their simultaneous identity as a curse and a gift to oncology. Indeed, the curtain calls for a better understanding Tfh cell biology, so that their potential can be used to benefit oncology. We discuss how prevalent Tfh cells in tumors can be beneficial in directing potent anti-tumour immune responses. We also review how the characterization of Tfh cells in tumors has now led to their identification as candidate biomarkers of response to immunotherapy, and how they are now being evaluated as targets for new immunotherapies leading to new clinical trials. The study concludes by emphasizing how the unique biological properties of Tfh cells can be leveraged to advance cancer treatment, ultimately aiming to enhance the effectiveness of clinical oncology practices., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Interstitial lung disease (ILD) is a common and fatal manifestation of antisynthetase syndrome (ASS). The aim of this study was to provide new insight into investigate peripheral blood lymphocytes, CD4+ T cells, cytokine levels and their relation to the clinical profile of untreated patients with ASS-ILD. The retrospective study population included thirty patients diagnosed with ASS-ILD and 30 healthy controls (HCs). Baseline clinical and laboratory data were collected for all subjects, including peripheral blood lymphocyte, CD4+ T cell subsets measured by flow cytometry, and serum cytokine levels measured by multiple microsphere flow immunofluorescence. Their correlations with clinical and laboratory findings were analyzed by Pearson's or Spearman's correlation analysis. In addition, the Benjamini-Hochberg method was used for multiple correction to adjust the p-values. Patients with ASS-ILD had lower CD8+ T cells, higher proportion of Th17 cells and Th17/Treg ratio than HCs. Serum cytokine levels (IL-1β, IL-6, IL-12, IL-17, IL-8, IL-2, IL-4, IL-10, TNF-α and IFN-γ) were higher in patients with ASS-ILD than HCs. Moreover, Th17/Treg ratio was negatively correlated with diffusing capacity of carbon monoxide (DLCO)%. Our study demonstrated abnormalities of immune disturbances in patients with ASS-ILD, characterized by decreased CD8+ T cells and an increased Th17/Treg ratio, due to an increase in the Th17 cells. These abnormalities may be the immunological mechanism underlying the development of ILD in ASS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Wall shear stress (WSS) is related to the pathogenesis of atherosclerosis. WSS is affected by a variety of hemodynamic factors, and there is still a lack of accurate and objective methods for measuring it. This study sought to evaluate hemodynamic changes in WSS maximum (max) , WSS mean , WSS minimum (min) in the common carotid artery of healthy adults of different ages using vascular vector flow mapping (VFM)., Methods: A retrospective analysis was conducted on 70 healthy volunteers aged 20-89 years who were recruited from our Ultrasound Department between February 2021 and June 2021. An ultrasound system with a 3-15 MHz probe was used to determine regions of interest (ROIs) of the common carotid artery. VFM-based WSS measurements were obtained by selecting ROIs with optimal image quality from three full cardiac cycles. The participants were divided into the following seven age groups: the 20s group, the 30s group, the 40s group, the 50s group, the 60s group, the 70s group, and the 80s group. The WSS parameters were compared among the age groups. An analysis of variance or a Kruskal-Wallis test was used to evaluate the difference among the groups, and a Pearson analysis and linear regression were used for the correlation and trend analysis., Results: The WSS parameters were quantified using vascular VFM software. The WSS max , WSS mean , WSS min differed among the age groups and gradually decreased with age, the elderly were significantly lower than the young. The Pearson correlation coefficient of the WSS max and age was -0.556 (P<0.001), that of the WSS mean and age was -0.461 (P<0.001), and that of the WSS min and age was -0.308 (P<0.001). The WSS parameters with age are negatively correlated the carotid intima-media thickness differed between the groups., Conclusions: The carotid WSS max , WSS mean , WSS min can be quantitatively and visually analyzed using the vascular VFM technique. In healthy adults of different ages, the carotid WSS max , WSS mean , WSS min decreased with age. Our findings about the normal values of carotid WSS maybe have clinical reference value for future studies., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-24-134/coif). F.C. serves as an unpaid editorial board member of Cardiovascular Diagnosis and Therapy from September 2023 to August 2025. All authors report that this work was supported by Shanghai Municipal Health Commission Health Industry Clinical Research Project (No. 202340181) and Shanghai Xuhui District-Academia Collaborative Project (Life and Health Sciences) (No. 23XHYD-22). Y.F. is employed by FUJIFILM Healthcare. The authors have no other conflicts of interest to declare., (2024 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Objective: Aortic Dissection (AD) is one of the most fatal acute diseases in cardiovascular diseases, with rapid onset and progression and a high fatality rate. This study aims to investigate the clinical values of non-enhancement peripheral pulse-gating rapid magnetic resonance imaging in deterministic diagnosis of AD., Methods: Aorta magnetic resonance imaging was performed in 21 healthy volunteers at a 1.5t MR scanner sequences including cardiac-gated and peripheral pulse-gated True-FISP and HASTE were carried out separately. Acquisition Time (TA), Signal to Noise Ratio (SNR), Contrast Noise Ratio (CNR), and entirety of vessel wall blood flow artifacts were measured and compared. A total of 56 AD cases were displayed by non-enhancement peripheral pulse-gating fast MR imaging, and the results were compared with pathological findings or CTA of the aorta. The dissection rupture, tear film, true and false lumen, thrombosis, hydropericardium, and the main branches of AD were evaluated respectively., Results: There were no significant differences in SNR, CNR, entirety of the vessel wall, and blood flow artifact between cardiac-gated and peripheral pulse-gated fast MR imaging. Non-enhancement pulse-gated fast scanning takes less TA time. By the pulse-gated non-enhancement fast MR imaging, the dissection rupture, tear film, true and false cavity, thrombosis, hydropericardium, and the main branches of aortic dissection were shown clearly. Multi-planar and multi-angle scans helped to show the extent of entrapment rupture, whereas partial complex tears or bi-directional tears were slightly less well visualized., Conclusion: Non-enhancement peripheral pulse-gated rapid magnetic resonance imaging can be used for deterministic diagnosis of AD., Competing Interests: Declaration of competing interest The authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 HCFMUSP. Published by Elsevier España, S.L.U. All rights reserved.)

Epithelial-to-mesenchymal transitions (EMTs) and extracellular matrix (ECM) remodeling are distinct yet important processes during carcinoma invasion and metastasis. Transforming growth factor β (TGF-β) and RAS, signaling through SMAD and RAS-responsive element-binding protein 1 (RREB1), jointly trigger expression of EMT and fibrogenic factors as two discrete arms of a common transcriptional response in carcinoma cells. Here, we demonstrate that both arms come together to form a program for lung adenocarcinoma metastasis and identify chromatin determinants tying the expression of the constituent genes to TGF-β and RAS inputs. RREB1 localizes to H4K16acK20ac marks in histone H2A.Z-loaded nucleosomes at enhancers in the fibrogenic genes interleukin-11 (IL11), platelet-derived growth factor-B (PDGFB), and hyaluronan synthase 2 (HAS2), as well as the EMT transcription factor SNAI1, priming these enhancers for activation by a SMAD4-INO80 nucleosome remodeling complex in response to TGF-β. These regulatory properties segregate the fibrogenic EMT program from RAS-independent TGF-β gene responses and illuminate the operation and vulnerabilities of a bifunctional program that promotes metastatic outgrowth., Competing Interests: Declaration of interests J.M. owns company stock in Scholar Rock. C.M.R. has consulted regarding oncology drug development with Amgen, Astra Zeneca, Chugai, Daiichi Sankyo, Hoffman-La Roche, and Jazz Pharmaceuticals; C.M.R. serves on the scientific advisory boards of Auron, Bridge Medicines, DISCO, Earli, and Harpoon Therapeutics. S.W.L. is a consultant and holds equity in Blueprint Medicines, ORIC Pharmaceuticals, Mirimus, PMV Pharmaceuticals, Faeth Therapeutics, and Senecea Therapeutics, and is a consultant for Fate Therapeutics. T.T. is a consultant and holds equity in Lime Therapeutics; the Tammela Lab receives research support from Ono Pharmaceuticals Co., Ltd. (unrelated to this work). T.T.’s spouse is an employee of Recursion Pharmaceuticals. R.P.K. is a co-founder of and consultant for Econic Biosciences., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Babesia orientalis, a protozoan parasite transmitted by the tick Rhipicephalus haemaphysaloides, holds significant economic importance along the Yangtze River. Key factors in the host invasion process include rhoptry neck proteins (RON2, RON4, and RON5) and apical membrane antigen 1 (AMA1). However, the intricacies of the interaction between AMA1 and RONs remain incompletely elucidated in B. orientalis. To better understand these crucial invasion components, the RON4 gene of B. orientalis (BoRON4) was cloned and sequenced. RON4 is 3468 base pairs long, encodes 1155 amino acids, and has a predicted molecular weight of 130 kDa. Bioinformatics analysis revealed a unique region (amino acid residues 109-452) in BoRON4, which demonstrates higher sensitivity to epitope activity. The BoRON4 gene was strategically truncated, amplified, and cloned into the pGEX-6p-1 vector for fusion expression. We successfully used the mouse polyclonal antibody to identify native BoRON4 in B. orientalis lysates. Furthermore, the corresponding BoRON4 protein band was detected in the water buffalo serum infected with B. orientalis, while no such band was observed in the control. Additionally, I-TASSER and Discovery Studio software were used to predict the tertiary structures of BoRON4 and its ligands, CH-PKA and CH-complex. These ligands can serve as lead compounds for the development of anti-babesiosis drugs. In conclusion, BoRON4 emerges as a promising candidate antigen for distinguishing water buffalo infected with B. orientalis from their normal counterparts. This study positions BoRON4 as a potential diagnostic antigen for babesiosis in water buffalo, contributing valuable insights to the field of parasitology., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pidotimod is a chiral drug that possesses two chiral centers, resulting in three isomeric impurities (analytes, A). This study employs electrospray ionization ion trap mass spectrometry (ESI-MS) through collision-induced dissociation (CID) to investigate the chiral recognition of pidotimod and its three isomers to eliminate chromatographic separation. Three approaches were explored: (1) Protonated molecules in CID exhibited discriminative potential for diastereomers, with the ability to distinguish between S,S and R,R configurations, albeit with an R chiral value of ~1.8. However, differentiation between R,S and S,R configurations was not achievable. (2) Alkali adductions (lithium and sodium) only discerned diastereomers. The R chiral values of the diastereomers obtained from alkali adduct ions were significantly lower than those obtained from protonated ions. (3) Therefore, a third approach was used to address the challenge of distinguishing between R,S and S,R configurations, including the introduction of chiral references (ref) and transition metals (M II ) to form metal-bound complexes [M II (A)(ref)-H] + . Additionally, we synthesized a novel ligand, 4-(N-tert-butoxycarbonyl [Boc]-L-prolinamido)phenol (denoted as ligand A), by modifying N-t-Boc-L-Pro with 2-aminophenol, which, in combination with Cu II and Ni II , enabled simultaneous differentiation of all four isomers. Cu II complexes exhibited significant chiral selectivity between R,S and S,R configurations. Density functional theory calculations were performed to further elucidate the stereodynamic behavior and stoichiometry of these ions in the gas phase. These calculations revealed the interaction energy and coordination sites of the precursor ions in the gas phase, correlating well with MS/MS experiment results. Additionally, the logarithm of the Cu II complexes' characteristic fragment ion abundance ratio demonstrated a strong linear relationship with enantiomeric excess (ee). This study presents a novel strategy for chiral drug quality control that eliminates chromatographic separation., (© 2024 Wiley Periodicals LLC.)

This study aims at developing a dataset for determining the presence of carotid artery plaques in ultrasound images, composed of 1761 ultrasound images from 1165 participants. A deep learning architecture that combines bilinear convolutional neural networks with residual neural networks, known as the single-input BCNN-ResNet model, was utilized to aid clinical doctors in diagnosing plaques using carotid ultrasound images. Following training, internal validation, and external validation, the model yielded an ROC AUC of 0.99 (95% confidence interval: 0.91 to 0.84) in internal validation and 0.95 (95% confidence interval: 0.96 to 0.94) in external validation, surpassing the ResNet-34 network model, which achieved an AUC of 0.98 (95% confidence interval: 0.99 to 0.95) in internal validation and 0.94 (95% confidence interval: 0.95 to 0.92) in external validation. Consequently, the single-input BCNN-ResNet network model has shown remarkable diagnostic capabilities and offers an innovative solution for the automatic detection of carotid artery plaques.

Breast cancer (BC) significantly contributes to cancer-related mortality in women, underscoring the criticality of early detection for optimal patient outcomes. Mammography is a key tool for identifying and diagnosing breast abnormalities; however, accurately distinguishing malignant mass lesions remains challenging. To address this issue, we propose a novel deep learning approach for BC screening utilizing mammography images. Our proposed model comprises three distinct stages: data collection from established benchmark sources, image segmentation employing an Atrous Convolution-based Attentive and Adaptive Trans-Res-UNet (ACA-ATRUNet) architecture, and BC identification via an Atrous Convolution-based Attentive and Adaptive Multi-scale DenseNet (ACA-AMDN) model. The hyperparameters within the ACA-ATRUNet and ACA-AMDN models are optimized using the Modified Mussel Length-based Eurasian Oystercatcher Optimization (MML-EOO) algorithm. The performance is evaluated using a variety of metrics, and a comparative analysis against conventional methods is presented. Our experimental results reveal that the proposed BC detection framework attains superior precision rates in early disease detection, demonstrating its potential to enhance mammography-based screening methodologies., (© 2024. The Author(s).)

Objective: To investigate the distribution and activation of B-cell subpopulations in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKis) and to analyze their correlation with disease remission., Methods: Peripheral blood samples were collected from 23 adult healthy controls and 58 RA patients, 31 of whom were treated with JAKis and assessed during a 24-month follow-up. The number of peripheral B-cell subpopulations (including naive B cells, nonswitched memory B (NSMB) cells, switched memory B cells, and double-negative B cells), their activation, and phosphorylation of SYK and AKT upon B-cell receptor (BCR) stimulation in each population were analyzed by flow cytometry., Results: Compared with that in healthy controls, the frequency of NSMB cells was significantly lower in new-onset untreated RA patients. However, expression of CD40, CD80, CD95, CD21 low and pAKT significantly increased in these NSMB cells. Additionally, the number of NSMB cells correlated negatively with DAS28-ESR and IgG and IgA levels in these patients; expression of CD80, CD95 and CD21 low on NSMB cells correlated positively with DAS28-ESR and IgG and IgA levels. After treatment with JAKis, the serum IgG concentration significantly decreased in RA patients in remission, but CD40, CD95 and pAKT levels in NSMB cells significantly decreased., Conclusion: RA patients present different B-cell subpopulations, in which the frequency of NSMB cells is negatively associated with disease activity. However, treatment with JAKis can inhibit activation of NSMB cells, restore the balance of kinase phosphorylation, and facilitate disease remission in RA patients., (© 2024. The Author(s).)

Interleukin-1β (IL-1β) contributes to interstitial lung disease (ILD) and pulmonary fibrosis (PF), thus representing a potential therapeutic target for PF. In this study, we first verified the increased expression of IL-1β in human fibrotic lung specimens and mouse lung tissues after intratracheal (i.t.) instillation of bleomycin (BLM), after which the pro-inflammatory and pro-fibrotic effects of recombinant IL-1β were tested in mice. The results above suggested that vaccination against IL-1β could be an effective strategy for managing PF. An anti-IL-1β vaccine (PfTrx-IL-1β) was designed by incorporating two IL-1β-derived polypeptides, which have been verified as the key domains that mediate the binding of IL-1β to its type I receptor, into Pyrococcus furiosus thioredoxin (PfTrx). The fusion protein PfTrx-IL-1β was prepared by using E. coli expression system. The vaccine was well tolerated; it induced robust and long-lasting antibody responses in mice and neutralized the biological activity of IL-1β, as shown in cellular assays. Pre-immunization with PfTrx-IL-1β effectively protected mice from BLM-induced lung injury, inflammation, and fibrosis. In vitro experiments further showed that anti-PfTrx-IL-1β antibodies counteracted the effects of IL-1β concerning pro-inflammatory and pro-fibrotic cytokine production by primary mouse lung fibroblast, macrophages (RAW264.7), and type II alveolar epithelial cell (A549), primary mouse lung fibroblast activation and epithelial-mesenchymal transition (EMT) of alveolar epithelial cells. In addition, the vaccination did not compromise the anti-infection immunity in mice, as validated by a sepsis model. Our preliminary study suggests that the anti-IL-1β vaccine we prepared has the potential to be developed as a therapeutic measure for PF. Further experiments are warranted to evaluate whether IL-1β vaccination has the capacity of inhibiting chronic progressive PF and reversing established PF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: This study aims to assess the current research status, focus areas, and developmental trends in nasopharyngeal carcinoma (NPC) through a bibliometric analysis., Methods: Articles focusing on NPC published from 2000 to 2023 were retrieved from the Web of Science database. VOSviewer and CiteSpace were used for bibliometric and visual analysis., Results: A total of 14516 related publications were retrieved. There has been a steady increase in the number of NPC-related publications from 2000 to 2023. China was the dominant country in this field with 8948 papers (61.64%), followed by the USA (2234, 15.39%). Sun Yat-sen University was the most influential institution, while Ma J was the most prolific author. Furthermore, Head And Neck-journal For The Sciences And Specialties Of The Head And Neck was the most prolific journal. International Journal of Radiation Oncology Biology Physics had the highest total citation counts. "Introduction chemotherapy", "Concurrent chemotherapy", "Epithelial-mesenchymal transition", "Cancer stem cells", "MicroRNAs", "LncRNA", "Exosomes", and "Biomarker" were the most common keywords. The reference "Chen YP, 2019, Lancet" had the highest citations and strong outbreak value., Conclusion: The past two decades have witnessed a significant increase in research on NPC. The optimization of treatment mode is the most widely studied aspect at present. The mechanism of occurrence and development and the most favorable diagnostic and therapeutic targets are the research hotspots in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 An, Liu, Lin, He and He.)

Pediatric patients with coronary artery lesions (CALs) after Kawasaki disease (KD) may be complicated with myocardial ischemia. Although previous studies in adults have proven the diagnostic value of 99m Tc-MIBI myocardial perfusion imaging (MPI) for ischemic heart disease, its feasibility and accuracy in this pediatric population remain uncertain. In this retrospective study, we collected data of 177 pediatric patients (Age range: 6 months to 14 years) who had undergone MPI and coronary artery angiography (CAG) between July 2019 and February 2023. Using the positive result of CAG as the reference standard of myocardial ischemia, we compared the results of 99m Tc-MIBI MPI with other non-invasive examinations, including cardiac magnetic resonance imaging (CMRI), echocardiogram, and comprehensive electrocardiogram-related examinations. All patients finished adenosine triphosphate stress MPI without major side effects. The sensitivity of MPI was 79.17%, which was greater than CMRI and echocardiogram (P < 0.05). The negative predictive value and the accuracy of MPI were 89.9% and 71.75%, indicating the advantages over others. Composite monitoring strategy of MPI and CMRI effectively improved the diagnostic performance (P < 0.001). In 4 cases diagnosed with myocardial ischemia by "MPI + CMRI," despite the absence of significant stenosis, multiple giant coronary artery aneurysms (GCAA) were all observed in CAG. 99m Tc-MIBI MPI is the preferred non-invasive examination for detecting myocardial ischemia in pediatric patients with CAL after KD. When combined with CMRI, it can enhance diagnostic accuracy. Multiple GCAAs without stenosis may be an isolated risk factor of myocardial ischemia., (© 2024. The Author(s).)

Human babesiosis is a tick-borne disease caused by Babesia pathogens. The disease, which presents with malaria-like symptoms, can be life-threatening, especially in individuals with weakened immune systems and the elderly. The worldwide prevalence of human babesiosis has been gradually rising, prompting alarm among public health experts. In other pathogens, genetic techniques have proven to be valuable tools for conducting functional studies to understand the importance of specific genes in development and pathogenesis as well as to validate novel cellular targets for drug discovery. Genetic manipulation methods have been established for several non-human Babesia and Theileria species and, more recently, have begun to be developed for human Babesia parasites. We have previously reported the development of a method for genetic manipulation of the human pathogen Babesia duncani . This method is based on positive selection using the hDHFR gene as a selectable marker, whose expression is regulated by the ef-1aB promoter, along with homology regions that facilitate integration into the gene of interest through homologous recombination. Herein, we provide a detailed description of the steps needed to implement this strategy in B. duncani to study gene function. It is anticipated that the implementation of this method will significantly improve our understanding of babesiosis and facilitate the development of novel and more effective therapeutic strategies for the treatment of human babesiosis. Key features This protocol provides an effective means of transfection of B. duncani , enabling genetic manipulation and editing to gain further insights into its biology and pathogenesis. The protocol outlined here for the electroporation of B. duncani represents an advancement over previous methods used for B. bovis [1]. Improvements include higher volume of culture used during the electroporation step and an enhancement in the number of electroporation pulses. These modifications likely enhance the efficiency of gene editing in B. duncani , allowing for quicker and more effective selection of transgenic parasites., (©Copyright : © 2024 The Authors; This is an open access article under the CC BY-NC license.)

Background: Carotid plaques are major risk factors for stroke. Carotid ultrasound can help to assess the risk and incidence rate of stroke. However, large-scale carotid artery screening is time-consuming and laborious, the diagnostic results inevitably involve the subjectivity of the diagnostician to a certain extent. Deep learning demonstrates the ability to solve the aforementioned challenges. Thus, we attempted to develop an automated algorithm to provide a more consistent and objective diagnostic method and to identify the presence and stability of carotid plaques using deep learning., Methods: A total of 3,860 ultrasound images from 1,339 participants who underwent carotid plaque assessment between January 2021 and March 2023 at the Shanghai Eighth People's Hospital were divided into a 4:1 ratio for training and internal testing. The external test included 1,564 ultrasound images from 674 participants who underwent carotid plaque assessment between January 2022 and May 2023 at Xinhua Hospital affiliated with Dalian University. Deep learning algorithms, based on the fusion of a bilinear convolutional neural network with a residual neural network (BCNN-ResNet), were used for modeling to detect carotid plaques and assess plaque stability. We chose AUC as the main evaluation index, along with accuracy, sensitivity, and specificity as auxiliary evaluation indices., Results: Modeling for detecting carotid plaques involved training and internal testing on 1,291 ultrasound images, with 617 images showing plaques and 674 without plaques. The external test comprised 470 ultrasound images, including 321 images with plaques and 149 without. Modeling for assessing plaque stability involved training and internal testing on 764 ultrasound images, consisting of 494 images with unstable plaques and 270 with stable plaques. The external test was composed of 279 ultrasound images, including 197 images with unstable plaques and 82 with stable plaques. For the task of identifying the presence of carotid plaques, our model achieved an AUC of 0.989 (95% CI: 0.840, 0.998) with a sensitivity of 93.2% and a specificity of 99.21% on the internal test. On the external test, the AUC was 0.951 (95% CI: 0.962, 0.939) with a sensitivity of 95.3% and a specificity of 82.24%. For the task of identifying the stability of carotid plaques, our model achieved an AUC of 0.896 (95% CI: 0.865, 0.922) on the internal test with a sensitivity of 81.63% and a specificity of 87.27%. On the external test, the AUC was 0.854 (95% CI: 0.889, 0.830) with a sensitivity of 68.52% and a specificity of 89.49%., Conclusion: Deep learning using BCNN-ResNet algorithms based on routine ultrasound images could be useful for detecting carotid plaques and assessing plaque instability., Competing Interests: ZY, YuW, WC, and LD were employed by Infervision. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 He, Yang, Wang, Chen, Diao, Wang, Yuan, Li, Zhang, He and Shen.)

Background: The prevalence of multiple nosocomial infections (MNIs) is on the rise, however, there remains a limited comprehension regarding the associated risk factors, cumulative risk, probability of occurrence, and impact on length of stay (LOS)., Method: This multicenter study includes all hospitalized patients from 2020 to July 2023 in two sub-hospitals of a tertiary hospital in Guangming District, Shenzhen. The semi-Markov multi-state model (MSM) was utilized to analyze risk factors and cumulative risk of MNI, predict its occurrence probability, and calculate the extra LOS of nosocomial infection (NI)., Results: The risk factors for MNI include age, community infection at admission, surgery, and combined use of antibiotics. However, the cumulative risk of MNI is lower than that of single nosocomial infection (SNI). MNI is most likely to occur within 14 days after admission. Additionally, SNI prolongs LOS by an average of 7.48 days (95% Confidence Interval, CI: 6.06-8.68 days), while MNI prolongs LOS by an average of 15.94 days (95% CI: 14.03-18.17 days). Furthermore, the more sites of infection there are, the longer the extra LOS will be., Conclusion: The longer LOS and increased treatment difficulty of MNI result in a heavier disease burden for patients, necessitating targeted prevention and control measures., (© 2024. The Author(s).)

Babesia duncani ( B. duncani ), a protozoan parasite prevalent in North America, is a significant threat for human health. Given the regulatory role of pyruvate kinase I (PyK I) in glycolytic metabolism flux and ATP generation, PyK I has been considered the target for drug intervention for a long time. In this study, B. duncani PyK I (BdPyK I) was successfully cloned, expressed, and purified. Polyclonal antibodies were confirmed to recognize the native BdPyK I protein (56 kDa) using Western blotting. AlphaFold software predicted the three-dimensional structure of BdPyK I, and molecular docking with small molecules was conducted to identify potential binding sites of inhibitor on BdPyK I. Moreover, inhibitory effects of six inhibitors (tannic acid, apigenin, shikonin, PKM2 inhibitor, rosiglitazone, and pioglitazone) on BdPyK I were examined under the optimal enzymatic conditions of 3 mM PEP and 3 mM ADP, and significant activity reduction was found. Enzyme kinetics and growth inhibition assays further confirmed the reliability of these inhibitors, with PKM2 inhibitor, tannic acid, and apigenin exhibiting the highest selectivity index as specific inhibitors for B. duncani . Subsequently, key amino acid residues were mutated in both BdPyK I and Homo sapiens pyruvate kinase I (HPyK I), and two differential amino acid residues (isoleucine and phenylalanine) were identified between HPyK I and BdPyK I through PyK activity detection experiments. These findings lay foundation for understanding the role of PyK I in the growth and development of B. duncani , providing insights for babesiosis prevention and drug development.

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck tumor that is influenced by a variety of molecular factors during its pathogenesis. Among these, the phosphatase and tensin homolog (PTEN) plays a crucial role in regulatory networks. This article systematically reviews the multifaceted functions of PTEN in NPC, including its roles in inhibiting cell proliferation, regulating migration and invasion, promoting autophagy and apoptosis, and influencing resistance to radiotherapy. Molecular factors such as long non-coding RNA, microRNA (miRNA), and circular RNA can modulate PTEN through various pathways, thereby impacting the biological behavior of NPC. In addition, PTEN is involved in regulating the tumor microenvironment of NPC, and its interaction with the Epstein-Barr virus has also recently become a focus of research. A comprehensive understanding of the PTEN regulatory network provides a foundation for future personalized and targeted therapeutic strategies. This study expands our understanding of the pathogenesis of NPC and suggests new directions in the field of tumor biology and NPC treatment., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Background: This study aimed to investigate the association between abdominal aortic calcification (AAC) and coronary heart disease (CHD) in essential hypertension (EH)., Methods: This study included patients diagnosed with EH during the 2013-2014 NHANES survey cycle. The study cohort was categorized into the following four groups based on their AAC-24 score: no AAC (0); mild AAC (1-4); moderate AAC (5-15); and severe AAC (16-24). Logistic regression models were used to assess the association between AAC and CHD. Restricted cubic spline curves (RCS) were used to explore possible nonlinear relationships between AAC and CHD., Results: The prevalence of CHD was found to be higher in the moderate AAC and severe AAC groups than in the group without AAC (40.1% versus 30.9%, 47.7% versus 30.9%). On a continuous scale, the fully adjusted model showed a 7% increase in the risk of CHD prevalence per score increase in AAC [OR (95% CI) = 1.07 (1.03-1.11)]. On a categorical scale, the fully adjusted model showed the risk of CHD prevalence in EH patients with moderate AAC and severe AAC was 2.06 (95%CI, 1.23-3.45) and 2.18 (1.09-5.25) times higher than that in patients without AAC, respectively. The RCS curve suggested a dose-response linear relationship between AAC and CHD., Conclusion: These findings highlight that in patients with EH, a higher severity of AAC is associated with a higher risk of CHD prevalence.

Based on the association network of &quot;drug pair-disease&quot;, the effect characteristics of Astragali Radix-Chuanxiong Rhizoma drug pair in the treatment of ischemic stroke(IS) with Qi deficiency and blood stasis and the matching mechanism of the two were explored. Through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction Database, the effective chemical components of the drug pair were screened, and the candidate targets were predicted. Databa-ses such as GeneCards, DrugBank, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD) were searched to obtain gene targets related to IS. Through STRING and Cytoscape 3.9.1 software, the protein-protein interaction(PPI) network was constructed by using the interaction information of disease syndrome-related genes and candidate targets of drug pairs, and the core targets were screened according to the network topological feature values. Based on the Metascape platform and DAVID database, the biomolecular interaction information was integrated to analyze the Kyoto Encyclopedia of Genes and Genomes(KEGG) and mine biological functions, so as to further explore the mechanism of action and compatibility characteristics of Astragali Radix-Chuan-xiong Rhizoma. The results showed that the candidate biological process was mainly involved in the regulation of functional modules such as immune, blood circulation, neurotransmitter, and oxidative stress, and it was enriched in lipid and atherosclerosis, calcium signaling pathway, and platelet activation. Astragali Radix and Chuanxiong Rhizoma have their own characteristics. Astragali Radix has a regulatory response to growth factors while maintaining the body's immune balance, while Chuanxiong Rhizoma mainly improves the circulatory system and participates in hormone metabolism, so as to indicate the compatibility mechanism of Astragali Radix-Chuanxiong Rhizoma drug pair for multi-target and multi-pathway synergistic treatment of IS. Through further experimental verification, it was found that the Astragali Radix-Chuanxiong Rhizoma drug pair could significantly down-regulate the expression of key targets including TLR4, NF-κB, IL-1β, F2R, PLCβ1, and MYLK. This study preliminarily reveals that the Astragali Radix-Chuanxiong Rhizoma drug pair may play the three replenishing effects of promoting blood circulation, benefiting Qi, and clearing collaterals by correcting immune di-sorders, blood circulation disorders, and inflammation, which provide support for the clinical research on the subsequent improvement of Qi deficiency and blood stasis in the treatment of IS and provide a new idea for the analysis of modern biological connotation of the compatibility of seven emotions of traditional Chinese medicine.

This study aims to optimize the conditions for the formation of neutrophil extracellular traps(NETs) in vitro, so as to establish a relatively stable experimental research platform. Different conditions were compared, including commonly used laboratory animals(rats and mice) and a variety of cell sources(bone marrow neutrophils and peripheral blood neutrophils separated by percoll density gradient centrifugation). Different inducers like lipopolysaccharide(LPS) and phorbol 12-myristate 13-acetate(PMA) were used for induction in vitro. Myeloperoxidase(MPO)/citrullinated histone H3(CitH3)/DAPI immunofluorescence and cell free DNA(cf-DNA) content determination were used for comprehensive evaluation to screen the optimal conditions for the formation of NETs induced in vitro. Furthermore, the stability of the selected conditions for inducing the formation of NETs in vitro was evaluated by tetramethylpyrazine(TMP), an active component in Chinese herbal medicines. The results showed that coated poly-D-lysine(PDL) induced the formation of NETs in bone marrow neutrophils of mice to a certain extent. Both LPS and PMA significantly up-regulated the protein levels of MPO and CitH3 in mouse bone marrow neutrophils and elevated the cfDNA level in the supernatant of rat peripheral blood neutrophils. The cfDNA level in the PMA-induced group increased more significantly than that in the LPS-induced group(P&lt;0.05). The results of immunofluorescence staining showed that the expression of MPO and CitH3 in mouse bone marrow neutrophils, rat bone marrow neutrophils, and rat peripheral blood neutrophils were significantly increased after PMA induction, especially in rat peripheral blood neutrophils. TMP significantly down-regulated the protein levels of MPO, CitH3, and neutrophil elastase(NE) in rat peripheral blood neutrophils induced by PMA. In conclusion, treating the peripheral blood neutrophils of rats with PMA is the optimal condition for inducing the formation of NETs in vitro. This study provides an optimal platform for in vitro studies based on NETs and a basis for studying the effects of traditional Chinese medicines targeting NETs.

Objective: The objective of this study was to analyze the changes in plasma fibrinogen (FIB) levels during tocilizumab (TCZ) treatment in patients with rheumatic diseases, to clarify the incidence of hypofibrinogenemia and its possible risk factors, and to establish a nomogram model for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ., Methods: Clinical data of patients treated with TCZ at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to October 2021 were retrospectively analyzed to observe the incidence of hypofibrinogenemia in several rheumatic diseases at different time points. The risk factor of hypofibrinogenemia in RA patients treated with TCZ was determined by using Cox regression analysis. Based on the results of Cox regression analysis, a nomogram for predicting the probability of hypofibrinogenemia in rheumatoid arthritis (RA) patients treated with TCZ was established and validated through RStudio software., Results: A total of 83 TCZ-treated patients were enrolled in this study, and 32 (38.55%) patients developed hypofibrinogenemia during TCZ treatment. There were 8 males and 24 females in the FIB-reduced group, with an average age of 44.88 ± 18.39 years. Hypofibrinogenemia was most common in TCZ-treated patients with takayasu arteritis (TA) and RA. Hypofibrinogenemia typically occured within 3 months after TCZ treatment. In RA patients treated with TCZ, platelet distribution width, parathyroid hormone, bone mineral density, tender joint count, and swollen joint count were independent risk factors for the occurrence of hypofibrinogenemia. The nomogram based on the above risk factors could effectively predict the probability of hypofibrinogenemia in RA patients receiving TCZ., Conclusion: Although bleeding symptoms were not observed in this study, the incidence of hypofibrinogenemia remained high after TCZ treatment, usually occurring within 3 months of treatment. Therefore, it is necessary to monitor FIB levels during TCZ treatment. In addition, clinicians can use the nomogram model developed from this study to predict the incidence of hypofibrinogenemia after TCZ treatment in RA patients. Key Points • Hypofibrinogenemia often occurs during TCZ treatment for rheumatic diseases. • PDW, PTH, BMD, tender joint count, and swollen joint count are risk factors for the occurrence of hypofibrinogenemia. • It is necessary to monitor FIB levels during TCZ treatment to avoid bleeding tendency., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

This study aims to decipher the mechanism of tetramethylpyrazine(TMP) in regulating the migration of neural stem cells(NSCs) in the rat model of middle cerebral artery occlusion(MCAO) via the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)/C-X-C motif chemokine receptor 4(CXCR4) pathway. SD rats were randomized into sham, MCAO(model), and tetramethylpyrazine(TMP, 20 mg·kg~(-1) and 40 mg·kg~(-1)) groups. The neurological impairment was assessed by the modified neurological severity score(mNSS). The immunofluorescence assay was employed to detect the cells stained with both 5-bromodeoxyuridine(BrdU) and doublecortin(DCX) in the brain tissue. The effect of TMP on the migration of C17.2 cells was observed. Western blot was employed to determine the protein levels of Nrf2, HO-1, p62, NAD(P)H quinone oxidoreductase 1(NQO1), stromal cell-derived factor 1(SDF-1), and CXCR4 in the brain tissue and C17.2 cells. The results showed that after 7 days and 21 days of mode-ling, the mNSS and BrdU~+/DCX~+ cells were increased, and the expression of Nrf2 and CXCR4 in the brain tissue was up-regulated. Compared with the model group, TMP(40 mg·kg~(-1)) reduced the mNSS, increased the number of BrdU~+/DCX~+ cells, and up-regulated the expression of Nrf2, CXCR4, and SDF-1. In addition, TMP promoted the migration of C17.2 cells and up-regulated the expression of p62, Nrf2, HO-1, and NQO1 in a time-and dose-dependent manner. The expression was the highest at the time point of 12 h in the TMP(50 μg·mL~(-1)) group(P&lt;0.01). In conclusion, TMP activates the Nrf2/HO-1/CXCR4 pathway to promote the migration of NSCs to the ischemic area, thus exerting the therapeutic effect on the ischemia-reperfusion injury. This study provides experimental support for the application of TMP in ischemic stroke.

This study aimed to investigate the intervention effect of tetramethylpyrazine(TMP) combined with transplantation of neural stem cells(NSCs) on middle cerebral artery occlusion(MCAO) rat model and to explore the mechanism of TMP combined with NSCs transplantation on ischemic stroke based on the regulation of stem cell biological behavior. MCAO rats were randomly divided into a model group, a TMP group, an NSCs transplantation group, and a TMP combined with NSCs transplantation group according to neurological function scores. A sham group was set up at the same time. The neurological function score was used to evaluate the improvement of neurological function in MCAO rats after TMP combined with NSCs transplantation. The proliferation, migration, and differentiation of NSCs were evaluated by BrdU, BrdU/DCX, BrdU/NeuN, and BrdU/GFAP immunofluorescence labeling. The protein expression of stromal cell-derived factor 1(SDF-1), C-X-C motif chemokine receptor 4(CXCR4), as well as oxidative stress pathway proteins nuclear factor erythroid 2-related factor 2(Nrf2), Kelch-like ECH-associated protein 1(KEAP1), heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1) was detected by Western blot to study the migration mechanism of TMP combined with NSCs. The results showed that TMP combined with NSCs transplantation significantly improved the neurological function score in MCAO rats. Immunofluorescence staining showed a significant increase in the number of BrdU~+, BrdU~+/DCX~+, BrdU~+/NeuN~+, and BrdU~+/GFAP~+ cells in the TMP, NSCs transplantation, and combined treatment groups, with the combined treatment group showing the most significant increase. Further Western blot analysis revealed significantly elevated expression of CXCR4 protein in the TMP, NSCs transplantation, and combined treatment groups, along with up-regulated protein expression of Nrf2, HO-1, and NQO1, and decreased KEAP1 protein expression. This study showed that both TMP and NSCs transplantation can promote the recovery of neurological function by promoting the proliferation, migration, and differentiation of NSCs, and the effect of TMP combined with NSCs transplantation is superior. The mechanism of action may be related to the activation of the Nrf2/HO-1/CXCR4 pathway.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Functionally uncharacterized genes are an attractive repository to explore candidate oncogenes. It is demonstrated that C21orf58 displays an oncogenic role in promoting cell growth, tumorigenesis and sorafenib resistance of HCC cells by abnormal activation of STAT3 signaling. Mechanistically, a novel manner to regulate STAT3 signaling that adaptor C21orf58 forms a ternary complex is reveal with N-terminal domain of STAT3 and SH2 domain of JAK2, by which C21orf58 overactivates wild-type STAT3 by facilitating its phosphorylation mediated by JAK2, and hyper-activates of constitutively mutated STAT3 due to preferred binding with C21orf58 and JAK2. Moreover, it is validated that inhibition of C21orf58 with drug alminoprofen, selected by virtual screening, could effectively repress the viability and tumorigenesis of HCC cells. Therefore, it is identified that C21orf58 functions as an oncogenic adaptor, reveal a novel regulatory mechanism of JAK2/STAT3 signaling, explain the cause of abnormal activity of activated mutants of STAT3, and explore the attractive therapeutic potential by targeting C21orf58 in HCC., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Two-dimensional (2D) materials have received significant attention for their potential use in next-generation electronics, particularly in nonvolatile memory and neuromorphic computing. This is due to their simple metal-insulator-metal (MIM) sandwiched structure, excellent switching performance, high-density capability, and low power consumption. In this work, using comprehensive material simulations and device modeling, the thinnest monolayer hexagonal boron nitride (h-BN) atomristor is studied by using a MIM configuration with Ta electrodes. Our first-principles calculations predicted both a high resistance state (HRS) and a low resistance state (LRS) in this device. We observed that the presence of van der Waals (vdW) gaps between the Ta electrodes and monolayer h-BN with a boron vacancy (V B ) contributes to the HRS. The combination of metal electrode contact and the adsorption of Ta atoms onto a single V B defect (Ta B ) can alter the interface barrier between the electrode and dielectric layer, as well as create band gap states within the band gap of monolayer h-BN. These band gap states can shorten the effective tunneling path for electron transport from the left electrode to the right electrode, resulting in an increase in the current transmission coefficient of the LRS. This resistive switching mechanism in monolayer h-BN atomristors can serve as a theoretical reference for device design and optimization, making them promising for the development of atomristor technology with ultra-high integration density and ultra-low power consumption.

Curcumin (CUR) is a lipophilic natural polyphenol that can be isolated from the rhizome of turmeric. Studies have proposed that CUR possesses a variety of biological activities. Due to its anti-inflammatory and antioxidant properties, CUR shows promise in the treatment of inflammatory bowel disease, while its anti-obesity effects make it a potential therapeutic agent in the management of obesity. In addition, curcumin's ability to prevent atherosclerosis and its cardiovascular benefits further expand its potential application in the treatment of cardiovascular disease. Nevertheless, owing to the limited bioavailability of CUR, it is difficult to validate its specific mechanism of action in the treatment of diseases. However, the restricted bioavailability of CUR makes it challenging to confirm its precise mode of action in disease treatment. Recent research indicates that the oral intake of curcumin may lead to elevated levels of residual curcumin in the gastrointestinal system, hinting at curcumin's potential to directly influence gut microbiota. Furthermore, the ecological dysregulation of the gut microbiota has been shown to be critical in the pathogenesis of human diseases. This review summarizes the impact of gut dysbiosis on host health and the various ways in which curcumin modulates dysbiosis and ameliorates various diseases caused by it through the administration of curcumin.

Background: Babesia orientalis is an intra-erythrocytic protozoan parasite that causes babesiosis in water buffalo. The genome of B. orientalis has been reported and various genes have been accurately annotated, including heat shock proteins (HSP). Three B. orientalis HSPs (HSP90, HSP70 and HSP20) have been previously identified as potential antigenic targets. Here, a new validation strategy for the chaperone activities and cell protection characteristics of the three HSPs was developed in vitro., Methods: BoHSP20, BoHSP70 and BoHSP90B were amplified from cDNA, followed by cloning them into the pEGFP-N1 vector and transfecting the vector plasmid separately into 293T and Hela mammalian cells. Their expression and localization were determined by fluorescence microscopy. The biological functions and protein stability were testified through an analysis of the fluorescence intensity duration. Their role in the protection of cell viability from heat-shock treatments was examined by MTT assay (cell proliferation assay based on thiazolyl blue tetrazolium bromide)., Results: Fusion proteins pEGFP-N1-BoHSP20, pEGFP-N1-BoHSP70, and pEGFP-N1-BoHSP90B (pBoHSPs: pBoHSP20; pBoHSP70 and pBoHSP90B) were identified as 47 kDa/97 kDa/118 kDa with a 27 kDa GFP tag, respectively. Prolonged fluorescent protein half-time was observed specifically in pBoHSPs under heat shock treatment at 55 °C, and BoHSP20 showed relatively better thermotolerance than BoHSP70 and BoHSP90B. Significant difference was found between pBoHSPs and controls in the cell survival curve after 2 h of 45 °C heat shock., Conclusion: Significant biological properties of heat stress-associated genes of B. orientalis were identified in eukaryote by a new strategy. Fusion proteins pBoHSP20, pBoHSP70 and pBoHSP90B showed good chaperone activity and thermo-stability in this study, implying that BoHSPs played a key role in protecting B. orientalis against heat-stress environment during parasite life cycle. In conclusion, the in vitro model explored in this study provides a new way to investigate the biological functions of B. orientalis proteins during the host-parasite interaction., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

This study aims to explore the mechanism of aqueous extract of Strychni Semen(SA) in relieving pain in the rat model of rheumatoid arthritis(RA) via Toll-like receptor 4(TLR4)/tumor necrosis factor-α(TNF-α)/matrix metalloproteinase-9(MMP-9) signaling pathway. Firstly, the main chemical components of Strychni Semen were searched against TCMSP, TCMID, ETCM, and related literature, and the main targets of the chemical components were retrieved from TargetNet and SwissTargetPrediction. The main targets of RA and pain were searched against GeneCards, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD). Venny 2.1.0 was used to obtain the common targets shared by Strychni Semen, RA, and pain, and STRING and Cytoscape 3.6.1 were used to build the protein-protein interaction network. Then, molecular docking was carried out in AutoDock Vina. Finally, the rat model of type Ⅱ collagen-induced arthritis(CIA) was established. The up-down method and acetone method were employed to examine the mechanical pain threshold and cold pain threshold of rats, and the pain-relieving effect of SA on CIA rats was evaluated comprehensively. Hematoxylin-eosin(HE) staining was employed to evaluate the histopathological changes of joints in CIA rats. The expression levels of key target proteins was determined by immunohistochemistry and Western blot, and the mRNA levels of key targets were determined by real-time fluorescence quantitative polymerase chain reaction(real-time PCR). The results of network prediction showed that Strychni Semen may act on the TLR4/TNF-α/MMP-9 signaling pathway to exert the pain-relieving effect. The results of molecular docking showed that brucine, the main active component of SA, had strong binding ability to TLR4, TNF-α, and MMP-9. The results of animal experiments showed that SA improved the mechanical and cold pain sensitivity(P&lt;0.05, P&lt;0.01) and reduced the joint histopathological score of CIA rats(P&lt;0.01). In addition, medium and high doses of SA down-regulated the protein and mRNA levels of TNF-α, TLR4, and MMP-9(P&lt;0.05,P&lt;0.01). In conclusion, SA alleviated the mechanical pain sensitivity, cold pain sensitivity, and joint histopathological changes in CIA rats by inhibiting the over activation of TLR4/TNF-α/MMP-9 signaling pathway.

Based on the sarcoma receptor coactivator(Src)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, the mechanism of action of bulleyaconitine A in the treatment of bone destruction of experimental rheumatoid arthritis(RA) was explored. Firstly, key targets of RA bone destruction were collected through GeneCards, PharmGKB, and OMIM databa-ses. Potential targets of bulleyaconitine A were collected using SwissTargetPrediction and PharmMapper databases. Next, intersection targets were obtained by the Venny 2.1.0 platform. Protein-protein interaction(PPI) network and topology analysis were managed by utilizing the STRING database and Cytoscape 3.8.0. Then, Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were conducted in the DAVID database. AutoDock Vina was applied to predict the molecular docking and binding ability of bulleyaconitine A with key targets. Finally, a receptor activator of nuclear factor-κB(RANKL)-induced osteoclast differentiation model was established in vitro. Quantitative real-time polymerase chain reaction(qRT-PCR) was used to detect the mRNA expression levels of related targets, and immunofluorescence and Western blot were adopted to detect the protein expression level of key targets. It displayed that there was a total of 29 drug-disease targets, and Src was the core target of bulleyaconitine A in anti-RA bone destruction. Furthermore, KEGG enrichment analysis revealed that bulleyaconitine A may exert an anti-RA bone destruction effect by regulating the Src/PI3K/Akt signaling pathway. The molecular docking results showed that bulleyaconitine A had better bin-ding ability with Src, phosphatidylinositol-4,5-diphosphate 3-kinase(PIK3CA), and Akt1. The result of the experiment indicated that bulleyaconitine A not only dose-dependently inhibited the mRNA expression levels of osteoclast differentiation-related genes cathepsin K(CTSK) and matrix metalloproteinase-9(MMP-9)(P&lt;0.01), but also significantly reduced the expression of p-c-Src, PI3K, as well as p-Akt in vitro osteoclasts(P&lt;0.01). In summary, bulleyaconitine A may inhibit RA bone destruction by regulating the Src/PI3K/Akt signaling pathway. This study provides experimental support for the treatment of RA bone destruction with bulleyaconitine A and lays a foundation for the clinical application of bulleyaconitine A.

Primary myelofibrosis (PMF) patients frequently have JAK2 (V617F), CALR (exon 9), or MPL (W515 or exon 10) strong driver gene mutation, which triggers abnormal activation of the JAK2-STATs signaling pathway that plays a complex role in the occurrence of PMF. However, about 10-15% of PMF patients have no above typical mutations in these strong driver genes, known as being "triple-negative", which are associated with poor prognosis. In this paper, we reported a unique secondary acute myeloid leukemia (sAML) case transformed from triple-negative PMF combined with lung cancer and erythroderma occurrence at the same time, which has not been reported so far. Through whole blood exome sequencing, four novel noncanonical mutations were detected in key regulatory genes SH2B3 (Q748 and S710) and STAT5a (C350 and K354). Meanwhile, STAT5a-S710 and SH2B3-K354 noncanonical mutations gained strong malignant biofunction on promoting cell growth and tumorigenesis by accelerating the G1/S transition. In the mechanistic study, these pernicious phenotypes driven by noncanonical mutations might be initial PMF by activating p-STAT5a/c-Myc/CyclinD1 and p-STAT3/p-AKT/p-ERK1/2 signaling axes. Therefore, our study explored the deleterious roles of novel noncanonical mutations in STAT5a and SH2B3, which may serve as susceptibility genes and display the oncogenic biofunction in the progression of PMF to acute myeloid leukemia-M2a (AML-M2a)., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Competing Interests: The authors report no conflicts of interest in this communication.

The effect of structure on the vibration response was explored for four piano soundboards with different but commonly adopted structures. The vibration response was obtained using the free-vibration method, and the values of the dynamic modulus of elasticity and dynamic shear modulus obtained using the free-vibration frequency method ( E F and G F ) were compared with the dynamic modulus of elasticity obtained using the Euler beam method ( E E ) and dynamic shear modulus obtained using the free-plate torsional vibration method ( G T ), respectively. It was found that the soundboards with different structures had different vibration modes and that excitation at different locations highlighted different vibration modes. For all the soundboards analyzed, the E E and G T were higher than E F and G F by 2.2% and 24.3%, respectively. However, the trends of the results of these methods were the same. The four piano soundboards with different structures possessed varying dynamic moduli of elasticity and dynamic shear moduli. These rules are consistent with the grain directions of the soundboards and the anisotropy of the wood (the direction of the units of the soundboards). The results show that the vibration mode of the piano soundboard is complex. The dynamic elastic modulus of the soundboard can be calculated using the Euler beam method. The results provide a reference for studies on the vibration response, material selection, production technology, and testing of piano soundboards.

Osteoporosis is a systemic bone disease characterized by low bone mineral density and bone microstructure damage, resulting in increased bone fragility and fracture risk. The present study aimed to identify key genes and functionally enriched pathways in osteoporotic patients. Weighted Gene Co-expression Network Analysis (WGCNA) was applied to microarray datasets of blood samples of osteoporotic patients from the Sao Paulo Ageing & Health [SPAH] study (26 osteoporotic samples and 31 normal samples) to construct co-expression networks and identify hub gene. The results showed that HDGF, AP2M1, DNAJC6, TMEM183B, MFSD2B, IGKV1-5, IGKV1-8, IGKV3-7, IGKV3D-11, and IGKV1D-42 are genes which were associated with the disease status of osteoporosis. Differentially expressed genes are enriched in proteasomal protein catabolic process, ubiquitin ligase complex, and ubiquitin-like protein transferase activity. Functional enrichment analysis demonstrated that genes in the tan module were enriched in immune-related functions, indicating that the immune system plays a critical role in osteoporosis. Validation assay demonstrated that the HDGF, AP2M1, TMEM183B, and MFSD2B levels were decreased in osteoporosis samples compared with healthy controls, while the levels of IGKV1-5, IGKV1-8, and IGKV1D-42 were increased in osteoporosis samples compared with healthy controls. In conclusion, our data identified and validated the association of HDGF, AP2M1, TMEM183B, MFSD2B, IGKV1-5, IGKV1-8, and IGKV1D-42 with osteoporosis in elderly women. These results suggest that these transcripts have potential clinical significance and may help to explain the molecular mechanisms and biological functions of osteoporosis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethnopharmacological Relevance: Yiqi Jiedu formula (YQJDF), rooted in the traditional Chinese medicinal principle of "tonifying qi and detoxifying", is remarkably efficacious in the clinical treatment of nasopharyngeal carcinoma (NPC). Previous studies have shed light on some of its anti-NPC effects and mechanisms, but the responsible pharmacological substances and their precise mechanisms of action remain unclear., Aim of the Study: The purpose of this study was to identify components of YQJDF that entered the bloodstream and to investigate their mechanisms of action against NPC through network pharmacology and serum metabolomics., Material and Methods: Components of YQJDF in serum were identified using liquid chromatography-tandem mass spectrometry. With these serum species as the focus of our research, network pharmacology analysis was used to identify active compounds and target genes that might mediate the efficacy of YQJDF in the treatment of NPC. Following establishment of an NPC xenograft model in nude mice, a non-targeted metabolomics approach was adopted to identify significant serum metabolites and metabolic pathways influenced by YQJDF., Results: Thirty-six components of YQJDF were identified, primarily consisting of alkaloids, phenylpropanoids, and flavonoids. Notably, pathways such as PI3K/AKT, factors associated with Epstein-Barr virus infection, IL-17 signaling, and lipid metabolism, were highlighted as potential therapeutic targets of YQJDF during NPC treatment. Additionally, our findings suggested that YQJDF modified the metabolism of arginine and proline in the serum of mice bearing nasopharyngeal tumor grafts., Conclusions: This study identified the primary active components of YQJDF, highlighting its holistic role in the treatment of NPC through multiple targets and pathways. Furthermore, our findings provided a roadmap for future research into the mechanism of YQJDF in the therapy of NPC, setting the stage for its clinical application., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Copy number variations (CNVs) play a vital role in regulating genes expression and tumorigenesis. We explored the copy number alterations in early-stage lung adenocarcinoma using high-throughput sequencing and nucleic acid flight mass spectrometry technology, and found that 8q22.1-22.2 is frequently amplified in lung adenocarcinoma tissues. COX6C localizes on the region and its expression is notably enhanced that driven by amplification in lung adenocarcinoma. Knockdown of COX6C significantly inhibits the cell proliferation, and induces S-G2/M cell cycle arrest, mitosis deficiency and apoptosis. Moreover, COX6C depletion causes a deficiency in mitochondrial fusion, and impairment of oxidative phosphorylation. Mechanistically, COX6C-induced mitochondrial deficiency stimulates ROS accumulation and activates AMPK pathway, then leading to abnormality in spindle formation and chromosome segregation, activating spindle assemble checkpoint, causing mitotic arrest, and ultimately inducing cell apoptosis. Collectively, we suggested that copy amplification-mediated COX6C upregulation might serves as a prospective biomarker for prognosis and targeting therapy in patients with lung adenocarcinoma., (© 2024. The Author(s).)

Purpose: This study aimed to assess the knowledge, attitudes and practices (KAP) among middle-aged and elderly population towards ultrasound screening for strokes., Patients and Methods: This web-based cross-sectional study was conducted between March, 2023, and May, 2023 at Shanghai Eighth People's Hospital. A self-designed questionnaire was developed to collect demographic information of middle-aged and elderly population and assess their knowledge, attitudes and practices toward ultrasound screening for strokes., Results: A total of 552 participants enrolled in this study, among them 151 (27.36%) aged above 60 years old, 306 (55.43%) resided in rural area, 239 (43.30%) possessed educational attainment at the level of junior college, college or above. The mean knowledge, attitudes and practice scores were 5.53 ± 2.56, 40.22 ± 5.60 and 38.30 ± 7.38, respectively. Pearson's analysis was performed to assess the relationship between knowledge, attitudes, and practices. It was shown that knowledge and attitudes were positively correlated (r = 0.544, P < 0.001), and knowledge and practices were also positively correlated (r = 0.404, P < 0.001). Additionally, there was a positive correlation between attitude and practice scores (r = 0.566, P < 0.001)., Conclusion: The results of this study demonstrate that the middle-aged and elderly population exhibited insufficient knowledge, positive attitudes, and moderate practices towards ultrasound screening for strokes. There is a need to improve the understanding of stroke risk factors, symptoms, and emergency measures among this population., Competing Interests: The author reports no conflicts of interest in this work., (© 2024 Wang et al.)

Mitochondrial transcription termination factor 3 (MTERF3) negatively regulates mitochondrial DNA transcription. However, its role in hepatocellular carcinoma (HCC) progression remains elusive. Here, we investigate the expression and function of MTERF3 in HCC. MTERF3 is overexpressed in HCC tumor tissues and higher expression of MTERF3 positively correlates with poor overall survival of HCC patients. Knockdown of MTERF3 induces mitochondrial dysfunction, S-G2/M cell cycle arrest and apoptosis, resulting in cell proliferation inhibition. In contrast, overexpression of MTERF3 promotes cell cycle progression and cell proliferation. Mechanistically, mitochondrial dysfunction induced by MTERF3 knockdown promotes ROS accumulation, activating p38 MAPK signaling pathway to suppress HCC cell proliferation. In conclusion, ROS accumulation induced by MTERF3 knockdown inhibits HCC cell proliferation via p38 MAPK signaling pathway suggesting a promising target in HCC patients., (© 2024. The Author(s).)

Introduction: This study aimed to investigate the associations of digital ulcers (DUs) in patients with systemic sclerosis (SSc)., Methods: This retrospective study investigated the demographic characteristics, specific autoantibodies, organ involvement, and laboratory tests in patients with SSc from our hospital., Results: This study enrolled 144 patients with SSc. The DU+ group consisted of 15 (10.4%) patients. Patients with SSc having DUs have longer disease duration, higher fibrinogen, higher fibrin degradation product, and lower cholesterol. None of the patients used cholesterol-lowering drugs before onset of DUs. The study also demonstrated a higher prevalence of anti-dsDNA and anti-histone antibodies in patients with SSc with DUs. Anti-dsDNA antibody is a specific antibody for SLE with a specificity of 96-99%. A total of 86.1% (124/144) of patients suffered from diffuse cutaneous SSc, and 28.5% (41/144) of patients suffered from overlap syndrome., Conclusion: Our study indicated that patients with SSc with fibrinogen of &gt;2.895 g/L (p = 0.043) and cholesterol of &lt;3.340 mmol/L (p = 0.036), which is equal to 129.258 mg/dL, are at high risk of developing DUs., (© 2024 S. Karger AG, Basel.)

Nasopharyngeal carcinoma (NPC) is a prevalent cancerous tumor that affects the head and neck region. Recent studies have provided compelling evidence indicating the significant involvement of microRNAs (miRNAs) in the development and progression of NPC. This review aims to present a comprehensive summary of the current knowledge regarding miRNA signatures in NPC, encompassing their expression patterns, molecular mechanisms, and potential therapeutic implications. Initially, the article outlines the aberrant expression of miRNAs in NPC and elucidates their roles in tumor initiation, invasion, and metastasis. Subsequently, the underlying molecular mechanisms of miRNA-mediated regulation of NPC-associated signaling pathways are discussed. Additionally, the review highlights the potential clinical applications of miRNAs as diagnostic and prognostic biomarkers, as well as their therapeutic potential in NPC treatment. In conclusion, this review underscores the critical involvement of miRNAs in NPC pathogenesis and underscores their promise as novel therapeutic targets for combating this devastating disease., Competing Interests: None., (AJCR Copyright © 2023.)

Background: Patients with nasopharyngeal carcinoma (NPC) who undergo longitudinal follow-up contrast-enhanced MRI are at risk of developing gadolinium deposition in their neural tissue, which may potentially harm them. Therefore, for these patients, a non-contrast-enhanced method is potentially beneficial as an alternative approach to predict enhancement in T1-weighted imaging (CE-T1WI). The traditional intravoxel incoherent motion (IVIM) is one of the non-contrast-enhanced methods; however, the severe distortion and signal loss limit its application in patients with NPC. The present study aimed to investigate whether non-distortion IVIM could reduce the need of CE-T1WI in the follow-up of patients with NPC., Methods: The patients with NPC underwent Turbo Spin-echo MVXD diffusion-weighted imaging-based IVIM (non-distortion IVIM) from November 2021 to May 2022. Firstly, thirty patients with NPC were underwent both non-distortion IVIM and traditional IVIM. The distortion rate (DR) of the non-distortion IVIM was compared with the traditional IVIM. Then, twenty-one NPC patients with tumors (areas >50mm 2 ) were included and correlation coefficient analysis was used to assess the relationship between their non-distortion IVIM and CE-T1WI. Linear regression analysis was performed to determine whether non-distortion IVIM predictors could predict CE-T1WI., Results: The correlation was observed between the parameter f of the non-distortion IVIM and the enhancement ratio of CE-T1WI (r = 0.543, P = 0.011). Moreover, the linear regression analysis revealed that f was an independent IVIM predictor of CE-T1WI in patients with NPC (P = 0.011). The DR of the non-distortion IVIM was significantly smaller than that of the traditional IVIM (0.12 ± 0.05 vs 0.48 ± 0.16, P < 0.001)., Conclusions: In patients with NPC, non-distortion IVIM showed potential clinical benefits to reduce the need for contrast agents, and it can independently predict the enhancement ratio., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Rhomboid domain-containing protein 3 (Rhbdd3) is a member of the rhomboid family, which can modulate the innate immune response in mammals. Nonetheless, the function and regulatory mechanism of fish Rhbdd3 during viral infection have not been characterized. In this study, Rhbdd3 was firstly cloned from common carp (Cyprinus carpio) and nominated as CcRhbdd3. Phylogenetically characterization showed that CcRhbdd3 shared a relatively long evolutionary distance with its mammalian homologs. In vivo experiment demonstrated that spring viraemia of carp virus (SVCV) infection promoted the expression of CcRhbdd3 in the liver, spleen, kidney and muscle tissues. Furthermore, overexpression of CcRhbdd3 significantly inhibited SVCV propagation, whereas knockdown of CcRhbdd3 markedly promoted SVCV replication in susceptible cells. RNA-seq and following validation showed that CcRhbdd3 overexpression upregulated the expression of several RIG-I signaling related genes, including TRIM25, TRAF2, MDA5, LGP2, IFN1, IFN3, RIG-I, IRF3 and ISG15. Moreover, CcRhbdd3 promoted the expression of NF-κB, a central immune regulator. Subcellular localization experiments showed that CcRhbdd3 was primarily distributed in the cytoplasm and co-localized with Rab5 in the early endosomes. Truncation experiments further demonstrated that the C-terminus containing the ubiquitin-binding associated domain, was crucial for both the subcellular localization and antiviral activity of CcRhbdd3. The findings in this study provide new insight into the host antiviral mechanism against aquatic RNA virus infection, and will facilitate the development of therapeutic strategies for the infection of SVCV., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

(1) Background: Epidemiological studies on the relationship between serum copper and hypertension are contradictory. We assessed the relationship between serum copper and blood pressure among adults in the United States. (2) Methods: We divided hypertension into two categories: treated hypertension and untreated hypertension. Linear or logistic regression analysis was applied to investigate the association between serum copper concentrations and blood pressure levels. (3) Results: As compared to quartile 1, the odds ratios (ORs) for untreated hypertension in quartiles 2, 3, and 4 were 1.02 (0.74-1.42), 1.23 (0.88-1.72), and 1.08 (0.74-1.58), respectively, in multivariable analysis (all p > 0.05). In non-hypertension, as compared with quartile 1, the β (95% CI) of systolic blood pressure for quartiles 2, 3, and 4 was -0.92 (-2.07-0.23), -0.05 (-1.30-1.20), and -0.48 (-1.83-0.88), respectively, in multivariable analysis (all p > 0.05). As compared to quartile 1, the ORs for treated hypertension in quartiles 2, 3, and 4 were 1.36 (0.88-2.10), 1.35 (0.87-2.09), and 1.56 (0.98-2.47), respectively, upon multivariable analysis including antihypertensive medication use as a covariate (all p > 0.05). Furthermore, 1SD increase in serum copper was non-significantly associated with 1.16 (0.97-1.37)-fold increased risk of hypertension in multivariable analysis ( p = 0.096). (4) Conclusion: In the present study, we discovered that the serum copper concentration was not related with hypertension or blood pressure levels. Antihypertensive drug use may distort the correlation between copper and blood pressure levels. Information on antihypertensive drug use may be taken into account when identifying new risk factors for hypertension.

Regulatory T cells (Tregs) are instrumental in maintaining immune tolerance and preventing destructive autoimmunity, but how heterogeneous Treg populations are established remains largely unknown. Here, we show that Zfp335 deletion in Tregs failed to differentiate into effector Tregs (eTregs) and lose Treg-suppressive function and that KO mice exhibited early-onset lethal autoimmune inflammation with unrestricted activation of conventional T cells. Single-cell RNA-Seq analyses revealed that Zfp335-deficient Tregs lacked a eTreg population and showed dramatic accumulation of a dysfunctional Treg subset. Mechanistically, Zfp335-deficient Tregs displayed reduced oxidative phosphorylation and dysfunctional mitochondrial activity. Further studies revealed that Zfp335 controlled eTreg differentiation by regulating fatty acid oxidation (FAO) through direct targeting of the FAO enzyme Hadha. Importantly, we demonstrate a positive correlation between ZNF335 and HADHA expression in human eTregs. Our findings reveal that Zfp335 controls FAO-driven eTreg differentiation to establish immune tolerance.

Deubiquitination is an important form of post-translational modification that regulates protein homeostasis. Ovarian tumor domain-containing proteins (OTUDs) subfamily member OTUD3 was identified as a deubiquitinating enzyme involved in the regulation of various physiological processes such as immunity and inflammation. Disturbances in these physiological processes trigger diseases in humans and animals, such as cancer, neurodegenerative diseases, diabetes, mastitis, etc. OTUD3 is aberrantly expressed in tumors and is a double-edged sword, exerting tumor-promoting or anti-tumor effects in different types of tumors affecting cancer cell proliferation, metastasis, and metabolism. OTUD3 is regulated at the transcriptional level by a number of MicroRNAs, such as miR-520h, miR-32, and miR101-3p. In addition, OTUD3 is regulated by a number of post-translational modifications, such as acetylation and ubiquitination. Therefore, understanding the regulatory mechanisms of OTUD3 expression can help provide insight into its function in human immunity and disease, offering the possibility of its use as a therapeutic target to diagnose or treat disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xu, He, Zhang, Di and Jiang.)