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Objectives: Although it has been reported that Interferon regulatory factor 1 (IRF1) inhibits Mycobacterium tuberculosis (Mtb) infection via inducible nitric oxide synthase (iNOS) in mice, how it counteracts with mycobacterial infection in human remains largely obscure. This study was conducted to investigated the effect of IRF1 on Mtb infection in human macrophages (Mϕs).Methods: We thus investigated the IRF1 expression by using PBMC and monocytes of pulmonary tuberculosis (TB) patients and human monocyte-derived macrophages (hMDMs) and THP-1-derived macrophages (THP-1-Mϕ). We used gain-of-function and loss-of-function approaches to explore the role of IRF1 on Mtb infection.Results: IRF1 was significantly induced in PBMC and monocytes of pulmonary TB patients in vivo and in human Mϕs in vitro. We demonstrated that IRF1 protects Mϕs from Mtb infection. Concurrently, IRF1 promotes the expression of several pro-inflammatory cytokines including IL-6, TNF-α and IL-8, indicating IRF1-mediated activation of innate immunity upon Mtb infection. Gain-of-function and loss-of-function approaches have demonstrated that IRF1 suppresses the mechanistic target of rapamycin (mTOR)/p70 S6 kinase (p70 S6K) cascade to exert its anti-Mtb effect.Conclusions: The discovery of a novel function of IRF1 in facilitating anti-mycobacterial effect through suppressing mTOR/p70 S6K signaling in Mϕs may provide a promoting therapeutic target for tuberculosis. [ABSTRACT FROM AUTHOR]

TWIST protein is critical to development and is activated in many cancers. TWIST regulates epithelial-mesenchymal transition, and is linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance. The majority of epithelial ovarian cancer (EOC) patients with metastatic disease respond well to first-line chemotherapy but most relapse with disease that is both metastatic and drug resistant, leading to a five-year survival rate under 20%. We are investigating the role of TWIST in mediating these relapses. We demonstrate TWIST-siRNA (siTWIST) and a novel nanoparticle delivery platform to reverse chemoresistance in an EOC model. Hyaluronic-acid conjugated mesoporous silica nanoparticles (MSN-HAs) carried siTWIST into target cells and led to sustained TWIST knockdown in vitro . Mice treated with siTWIST-MSN-HA and cisplatin exhibited specific tumor targeting and reduction of tumor burden. This platform has potential application for overcoming clinical challenges of tumor cell targeting, metastasis and chemoresistance in ovarian and other TWIST overexpressing cancers. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders because of their powerful anti-inflammatory properties; however, their effects on macrophage-mediated immune responses are not completely understood. In the present study, we found that GCs decreased LPS-mediated TBK1 activation and the expression of IFN-β, RANTES and CXCL-10; however, poly(dA:dT)-induced TBK1 activity and cytokine expression were not affected by GCs treatment. Furthermore, GCs decreased the expression of key autophagy-related genes (ATGs), including ATG5, ATG7 and ATG12, and inhibited autophagy in macrophages after LPS stimulation. However, GCs had no effect on poly(dA:dT)-mediated autophagy and ATG expression in macrophages. Collectively, this study demonstrates that GCs inhibit the TLR4-mediated innate immune response, but do not affect the cytosolic DNA sensing pathway. This provides new insights into the immunomodulatory mechanisms of GCs in macrophages, which may provide useful information for the clinical use of GCs in treating chronic inflammatory disorders. [ABSTRACT FROM AUTHOR]

Epithelial ovarian cancer (EOC) is the most deadly gynecologic malignancy on account of its late stage at diagnosis and frequency of drug resistant recurrences. Novel therapies to overcome these barriers are urgently needed. TWIST is a developmental transcription factor reactivated in cancers and linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance, making it a promising therapeutic target. In this work, we demonstrate the efficacy of TWIST siRNA (siTWIST) and two nanoparticle delivery platforms to reverse chemoresistance in EOC models. Polyamidoamine dendrimers and mesoporous silica nanoparticles (MSNs) carried siTWIST into target cells and led to sustained TWIST knockdown in vitro . Mice treated with cisplatin plus MSN-siTWIST exhibited lower tumor burden than mice treated with cisplatin alone, with most of the effect coming from reduction in disseminated tumors. This platform has potential application for overcoming the clinical challenges of metastasis and chemoresistance in EOC and other TWIST overexpressing cancers. [ABSTRACT FROM AUTHOR]

Alexithymia is associated with adverse developmental outcomes. However, this concept has been criticized for being heavily influenced by Western norms of emotional expression and for potentially pathologizing people from different cultural backgrounds. Furthermore, the widely employed variable-centered study approaches hinder research understanding of real-world alexithymia profiles. Using a person-centered approach, the current study investigated the alexithymia profiles among Chinese college students and tested the profiles' relations with childhood adversity and COVID-19 burnout. Four latent alexithymia profiles were identified. The High I profile (particular difficulty identifying feelings) emerged as a risk profile for childhood adversity and COVID-19 burnout. Our findings illustrate the heterogeneity of the alexithymia construct and represent a significant step toward expanding cross-cultural understanding of alexithymia profiles and their associations with related psychological constructs. When dealing with childhood adversity and COVID-19 burnout, health care programs should consider a specific alexithymia profile defined by difficulty identifying feelings. • Using a person-centered study method, this study revealed four latent alexithymia profiles among Chinese college students. • The High I profile (difficulty identifying feelings) emerged as a risk profile for childhood adversity. • The High I profile was also the risk profile for COVID-19 burnout. [ABSTRACT FROM AUTHOR]

Specific targeting of cell organelles is indispensable for bioimaging and diagnostics but remains a challenge due to the limitation of highly selective fluorescent targeting probes. Herein, we successfully designed a molecular fusion route to controllably synthesize bright orange fluorescent graphene quantum dots (GQDs). The relative nitrogen doping level of the GQDs reached 18.88 at%. The GQDs exhibited long-wavelength excitation fluorescence and photoluminescence (PL) stability. Femtosecond transient absorption spectroscopy elucidated that the sp2 cluster and the surface state's synergistic effect contributed to the PL. Furthermore, the most alluring discovery was that the GQDs had good biocompatibility and an unprecedented targeting capability for superselective nucleus imaging without staining cell organelles. Molecular dynamics simulations revealed that once the GQDs were transported across the plasma membrane, the higher the N-doping ratio of the GQDs was, and the easier the GQDs penetrated the membrane. The reason may stem from the compatibility of –NH 2 with lipid molecules, which is higher than that of –OH. Enriched nitrogen doping in GQDs is beneficial for crossing the cell membrane to the target nucleus. Our findings could provide scientific theory and a technical basis to design nucleus-targeting probes in the future. Enriched nitrogen-doping in graphene quantum dots enables a high-selective fluorescent probe for nucleus-targeting imaging. [Display omitted] • Bright orange fluorescent GQDs are controllably synthesized by a molecular fusion route. • The GQDs exhibited long-wavelength excitation fluorescence and PL stability. • The sp2 cluster and the surface state's synergistic effect contributed to the PL. • The GQDs had good biocompatibility and an unprecedented targeting capability for superselective nucleus imaging. • Enriched nitrogen doping up to 18.88 at% in GQDs is beneficial for crossing the cell membrane to the target nucleus. [ABSTRACT FROM AUTHOR]

Real-time semantic segmentation in traffic scenes plays an essential part in autonomous driving. The encoder–decoder-based network architecture can well combine the context information and detailed information required for the semantic segmentation task. Achieving a good balance between inference speed and accuracy is a crucial challenge, as considerable real-time semantic segmentation models process information in real-time at the expense of accuracy degradation. This paper presents an encoder–decoder network model based on Cross Stage Partial (CSP) block for real-time semantic segmentation in traffic scenes. Integrating the CSP block can not only lessen the computational overhead but also enhance the feature extraction ability of the network. In addition, we append the Fast Spatial Pyramid Pooling module to the backbone of the network, which can aggregate global information at a low computational cost. On NVIDIA RTX 3090, the middle model of our method can achieve a mean intersection over union (mIOU) of 80.8% at 64.3 frames per second (FPS) on the Cityscapes test set and an mIOU of 81.3% at 105.3 FPS on the CamVid Test Set. The large model of our method can realize an mIOU of 81.5% at 48.4 FPS on the test set of Cityscapes. Our source code is available at https://github.com/zhouliguo/cspsg. • Our method achieves real-time inference with relatively high precision. • Multi-scale models are flexible to implement in various scenarios. • The integration of the CSP block enhances the representation ability of the feature. [ABSTRACT FROM AUTHOR]

Stimulator of interferon gene (STING), an adaptor molecule in the immune system, is involved in mediating the response to viral and bacterial infections, anti-tumor immunity, autoimmune diseases, and lipid metabolism. There have been reports on the cloning and function of STING in humans, pigs, chickens, and cats; however, STING has not been characterized in non-human primates or monkeys to date. Therefore, in this study, the rhesus macaque (Macaca mulata) STING gene was cloned, and we performed preliminary functional tests to examine its role in the interferon (IFN) pathway. The M. mulatta STING complementary DNA was 1140 bp in length and encoded 380 amino acid residues. Phylogenetic analysis showed that Homo sapiens and M. mulatta STING are closely related and clustered on the same branch. M. mulatta STING was confirmed to increase the promoter activities of IFN-β, nuclear factor-κB, and interferon-sensitive response element, and STING overexpression increased the mRNA levels of IFN-α, IFN-β, and interferon regulatory factor 3. Infection of Marc-145 cells with porcine reproductive and respiratory syndrome virus activated STING, and its expression increased along with increases in viral multiplicity of infection titer and time. Moreover, STING expression was time- and dose-dependently up-regulated by poly (I:C) and poly (dA:dT) treatments in Marc-145 cells. In summary, these results highlight STING as a vital immune system signal protein in the IFN pathway. This study provides a basis for understanding the immune characteristics of M. mulatta , and may have important implications for both monkey and human diseases. • Macaca mulatta stimulator of interferon gene (STING) was cloned for the first time. • Human and M. mulatta STING show high sequence similarity and cluster on the same branch. • M. mulatta STING actives the interferon pathway. • PRRSV, poly(I:C), and poly(dA:dT) increase the STING expression level in monkey cells. [ABSTRACT FROM AUTHOR]

This study examined the mediating effect of regulatory emotional self-efficacy and the moderating effect of meaning in life on the relationship between social anxiety and subjective well-being among Chinese college students. Nine hundred and eight Chinese students (M age = 20.14, SD = 1.71; 49% males) completed self-reported questionnaires regarding social anxiety, regulatory emotional self-efficacy, meaning in life, and subjective well-being. Structural equation modeling (SEM) was used to determine the relation between social anxiety and subjective well-being and the moderated mediation model. The results revealed that regulatory emotional self-efficacy fully mediated the link between social anxiety and college students' subjective well-being. College students' meaning in life moderated the associations between social anxiety and college students' regulatory emotional self-efficacy and between regulatory emotional self-efficacy and subjective well-being. Particularly, the link between social anxiety and regulatory emotional self-efficacy was only significant for those with lower meaning in life. The association between regulatory emotional self-efficacy and subjective well-being was more robust for those with higher meaning in life. This study identified the critical factors associated with subjective well-being; it supplies empirical support for existing theories and provides practical implications for interventions aiming to improve Chinese college students' subjective well-being. [ABSTRACT FROM AUTHOR]