Chondrocyte loss is a prominent feature of osteoarthritis (OA). Autophagy is indispensable in maintaining the metabolic activities of cells exposed to deleterious stress. The contribution of microRNA ...signaling to chondrocyte autophagy in OA development remains elusive. We uncovered an association between poor autophagy and increased miR-128a expressions in articular chondrocytes of patients with end-stage knee OA and in a rat anterior cruciate ligament transection (ACLT) model for OA development. Cartilage matrix degradation and severe OA histopathology was evident upon forced miR-128a expression within the articular compartment. Intra-articular injections with miR-128a antisense oligonucleotide stabilized chondrocyte autophagy and slowed ACLT-mediated articular tissue destruction, including cartilage erosion, synovitis, osteophyte formation, and subchondral plate damage. In vitro, miR-128 signaling hindered Atg12 expression, LC3-II conversion, and autophagic puncta formation through targeting the 3'-untranslated region of Atg12. It increased apoptotic programs, diminishing cartilage formation capacity of articular chondrocytes. Inactivating histone methyltransferase EZH2 reduced methyl histone H3K27 enrichment in the miR-128a promoter and upregulated miR-128a transcription in inflamed chondrocytes. Taken together, miR-128a-induced Atg12 loss repressed chondrocyte autophagy to aggravate OA progression. EZH2 inactivation caused H3K27 hypomethylation to accelerate miR-128a actions. Interruption of miR-128a signaling attenuated chondrocyte dysfunction and delayed OA development. Our data provide new insights into how miR-128a signaling affects chondrocyte survival and articular cartilage anabolism and highlight the potential of miR-128a targeting therapy to alleviate knee OA.
3XMM J031820.8-663034, first detected by ROSAT in NGC 1313, is one of a few known transient ultraluminous X-ray sources (ULXs). In this paper, we present decades of X-ray data of this source from ...ROSAT, XMM-Newton, Chandra, and the Neil Gehrels Swift Observatory. We find that its X-ray emission experienced four outbursts since 1992, with a typical recurrent time ∼1800 days, an outburst duration ∼240-300 days, and a nearly constant peak X-ray luminosity ∼1.5 × 1039 erg s−1. The upper limit of X-ray luminosity at the quiescent state is ∼5.6 × 1036 erg s−1, and the total energy radiated during one outburst is ∼1046 erg. The spectra at the high luminosity states can be described with an absorbed disk blackbody, and the disk temperature increases with the X-ray luminosity. We compare its outburst properties with other known transient ULXs including ESO 243-49 HLX-1. As its peak luminosity only marginally puts it in the category of ULXs, we also compare it with normal transient black hole binaries. Our results suggest that the source is powered by an accreting massive stellar-mass black hole, and the outbursts are triggered by the thermal-viscous instability.
This report describes an ongoing Phase I clinical trial testing the safety of adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) in patients with primary hepatocellular ...carcinoma (HCC). Fifteen HCC patients were treated with their activated and expanded TILs following tumor resection. From a total of 17 patients with HCC, TIL were successfully expanded from 15 patients (88%), whereas two patients showed minimal or no expansion of TIL. Transient increase in the frequency of T cells was observed after adoptive transfer who was found only associated with grade I flu-like symptoms and malaise. After a median follow-up of 14 months, 15 patients (100%) were alive; and 12 patients (80%) showed no evidence of disease, 3 patients (patient 1,11,12) had tumor recurrence. The time to the diagnosis of tumor recurrence following therapy ranged from 105 to 261 days. These results indicate that immunotherapy with activated and expanded autologous TIL could be successfully performed with low toxicity, thus would serve as a novel treatment modality for patients with HCC.
Biliary tract infection (BTI), a commonly occurring abdominal disease, despite being extensively studied for its initiation and underlying mechanisms, continues to pose a challenge in the quest for ...identifying specific diagnostic biomarkers. Extracellular vesicles (EVs), which emanate from diverse cell types, serve as minute biological entities that mirror unique physiological or pathological conditions. Despite their potential, there has been a relatively restricted exploration of EV-oriented methodologies for diagnosing BTI. To uncover potent protein biomarkers for BTI patients, we applied a label-free quantitative proteomic method known for its unbiased and high-throughput nature. Furthermore, 192 differentially expressed proteins surfaced within EVs isolated from individuals afflicted with BTI. Subsequent GO and KEGG analyses pinpointed Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and Crumbs homolog 3 (CRB3) as noteworthy biomarkers. Validation via data analysis of plasma-derived EV samples confirmed their specificity to BTI. Our study leveraged an unbiased proteomic tool to unveil CEACAM1 and CRB3 as promising protein biomarkers in serum EVs, presenting potential avenues for the advancement of diagnostic systems for BTI detection.
Abstract
Ultraluminous X-ray bursts (ULXBs) are ultraluminous X-ray flares with a fast rise (∼1 minute) and a slow decay (∼1 hour), which are commonly observed in extragalactic globular clusters. ...Most ULXBs are observational one-off bursts, whereas five flares from the same source in NGC 5128 were discovered by Irwin et al. In this article, we propose a neutron star (NS)–white dwarf (WD) binary model with super-Eddington accretion rates to explain the repeating behavior of the ULXB source in NGC 5128. With an eccentric orbit, the mass transfer occurs at the periastron where the WD fills its Roche lobe. The ultraluminous X-ray flares can be produced by the accretion column around the NS magnetic poles. On the other hand, some repeating fast radio bursts (FRBs) were also found in extragalactic globular clusters. Repeating ULXBs and repeating FRBs are the most violent bursts in the X-ray and radio bands, respectively. We propose a possible association between the repeating ULXBs and the repeating FRBs. Such an association is worth further investigation by follow-up observations on nearby extragalactic globular clusters.
In this original study, we retrospectively reviewed the cases of nocardiosis diagnosed through culture and next-generation sequencing (NGS) methods between 2014 and 2018 in Huashan Hospital and found ...out that the latter way can not only improve the detection rate of
spp. but also greatly reduce the turnaround time. In addition, by comparing nocardiosis and non-nocardiosis patients both of whose samples had
spp. detected by NGS, we found that
's specific reads ranking among top two might be a satisfactory cutoff value for clinical diagnosis of the disease. Our study introduced the promising value of the NGS method in the rapid diagnosis of nocardiosis.
The role of emotions in augmented reality Soon, Pei‐Shan; Lim, Weng Marc; Gaur, Sanjaya Singh
Psychology & marketing,
11/2023, Letnik:
40, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Abstract
Augmented reality (AR) can induce emotions among its users. However, emotional valence is often studied with a singular focus (e.g., enjoyment), which disregards and overlooks the ...multifaceted nature of emotional valence. Taking a multifaceted perspective of emotional valence, this study aims to broaden understanding of how induced emotions can drive consumers’ inclination to use AR. A multifaceted emotion measurement scale was modified and utilized (
n
Study1
: 224), followed by two experimental studies (
n
Study2
: 214;
n
Study3
: 200). These experiments entailed a design wherein the experimental group explored products using an AR app while the control group navigated the mobile website of the same company devoid of any AR features. Our findings indicate that the use of AR instigates expressive emotions, further eliciting emotion components spanning both affective and physiological dimensions. In instances of positive emotions, at least two out of the three elicited emotion components consistently led to a heightened desire to engage with AR. Negative emotions produce no significant effects. Taken collectively, the principal theoretical contribution of this study lies in its elucidation of the components and elicitation patterns of emotions tied to AR, whereas the practical standpoint of these findings underscores the necessity for both developers and marketers to comprehend the pivotal role that the induction of positive expressive emotions plays in designing effective AR apps. These insights should therefore pave the way for more intuitively engaging and emotionally satisfying AR experiences for consumers.
Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and resistance to therapeutic agents; they are usually less sensitive to conventional cancer therapies, and could cause ...tumor relapse. An ideal therapeutic strategy would therefore be to selectively target and destroy CSCs, thereby preventing tumor relapse. The aim of the present study was to evaluate the effectiveness of dendritic cells (DCs) pulsed with antigen derived from CD105+ human renal cell carcinoma (RCC) CSCs against renal cancer cells in vitro and in vivo. We identified “stem‐like” characteristics of CD105+ cells in two human RCC cell lines: A498 and SK‐RC‐39. Loading with cell lysates did not change the characteristics of the DCs. However, DCs loaded with lysates derived from CD105+ CSCs induced more functionally specific active T cells and specific antibodies against CSCs, and clearly depressed the tumor growth in mice. Our results could form the basis for a novel strategy to improve the efficacy of DC‐based immunotherapy for human RCC.
GRS 1915+105 has been active for more than 26 years since it was discovered in 1992. There are hundreds of RXTE pointed observations on this source, and the quasi-regular flares with a slow rise and ...a sharp decrease (i.e., the "heartbeat" state) were recorded in more than 200 observations. The connections among the disk/corona, jet, and the disk wind at the heartbeat state have been extensively studied. In this work, we first perform a statistical analysis of the light curves and the X-ray spectra to investigate this peculiar state. We calculate the parameters for heartbeat cycles, including the recurrence time, the maximum and the minimum count rate, the flare amplitude, and the cumulative radiation for each cycle. The recurrence time has a bimodal distribution ranging from ∼20 to ∼200 s. The minimum count rate increases with increasing recurrence time; while the maximum count rate remains nearly constant around 2 Crab. Fitting the averaged spectrum for each observation, we find the strong correlations among the recurrence time, the apparent inner radius of the accretion disk (or the color correction factor), and the (nonthermal) X-ray luminosity. We suggest that the true inner edge of the accretion disk might always extend to the marginally stable orbit, while the change in corona size results in the observed correlations.
Gallbladder cancer (GBC) is a leading cause of cancer-related death worldwide, and its prognosis remains poor, with 5-year survival of approximately 5%. In this study, we analyzed the involvement of ...a novel proteoglycan, Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1), in the tumor progression and prognosis of human GBC.
SPOCK1 expression levels were measured in fresh samples and stored specimens of GBC and adjacent nontumor tissues. The effect of SPOCK1 on cell growth, DNA replication, migration and invasion were explored by Cell Counting Kit-8, colony formation, EdU retention assay, wound healing, and transwell migration assays, flow cytometric analysis, western blotting, and in vivo tumorigenesis and metastasis in nude mice.
SPOCK1 mRNA and protein levels were increased in human GBC tissues compared with those in nontumor tissues. Immunohistochemical analysis indicated that SPOCK1 levels were increased in tumors that became metastatic, compared with those that did not, which was significantly associated with histological differentiation and patients with shorter overall survival periods. Knockdown of SPOCK1 expression by lentivirus-mediated shRNA transduction resulted in significant inhibition of GBC cell growth, colony formation, DNA replication, and invasion in vitro. The knockdown cells also formed smaller xenografted tumors than control GBC cells in nude mice. Overexpression of SPOCK1 had the opposite effects. In addition, SPOCK1 promoted cancer cell migration and epithelial-mesenchymal transition by regulating the expression of relevant genes. We found that activation of the PI3K/Akt pathway was involved in the oncogenic functions of SPOCK1 in GBC.
SPOCK1 activates PI3K/Akt signaling to block apoptosis and promote proliferation and metastasis by GBC cells in vitro and in vivo. Levels of SPOCK1 increase with the progression of human GBC. SPOCK1 acts as an oncogene and may be a prognostic factor or therapeutic target for patients with GBC.
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