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Interferon regulatory factor 1 (IRF1) is a critical component of cell-intrinsic innate immunity that regulates both constitutive and induced antiviral defenses. Due to its short half-life, IRF1 function is generally considered to be regulated by its synthesis. However, how IRF1 activity is controlled post-translationally has remained poorly characterized. Here, we employed a proteomics approach to identify proteins interacting with IRF1, and found that CSNK2B, a regulatory subunit of casein kinase 2, interacts directly with IRF1 and constitutively modulates its transcriptional activity. Genome-wide CUT&RUN analysis of IRF1 binding loci revealed that CSNK2B acts generally to enhance the binding of IRF1 to chromatin, thereby enhancing transcription of key antiviral genes, such as PLAAT4 (also known as RARRES3/RIG1/TIG3). On the other hand, depleting CSNK2B triggered abnormal accumulation of IRF1 at AFAP1 loci, thereby down-regulating transcription of AFAP1, revealing contrary effects of CSNK2B on IRF1 binding at different loci. AFAP1 encodes an actin crosslinking factor that mediates Src activation. Importantly, CSNK2B was also found to mediate phosphorylation-dependent activation of AFAP1-Src signaling and exert suppressive effects against flaviviruses, including dengue virus. These findings reveal a previously unappreciated mode of IRF1 regulation and identify important effector genes mediating multiple cellular functions governed by CSNK2B and IRF1.

This paper examines the aerodynamic drag force acting on a tilt-rotor UAV that has three mini fans and a main rotor with a tilt mechanism. The mini fans are embedded in the nose and the left and right wings. The main rotor is located near the center of the vehicle, and its front half is surrounded by the trailing edge of the nose in rotary-wing mode. The downward airflow from the fans and the main rotor generates an aerodynamic drag force called momentum drag, which is linearly proportional to the airspeed of UAV. To verify the existence of momentum drag, parameter identification of drag coefficients is performed from experimental data where the UAV flies forward in rotary-wing mode. The drag force is also investigated using computational fluid dynamics simulations. These experimental and numerical results are consistent with theoretical results based on momentum theory.

Introduction: Hepato-splanchnic circulation influences the oxygenation of abdominal organs and is important in preventing a reduction in intradialytic blood volume. However, the association between changes in intradialytic hepato-splanchnic circulation and clinical factors remain unknown. Methods: We enrolled 91 hemodialysis (HD) patients (20 with intradialytic hypotension (IDH) and 71 without IDH). During HD, hepatic regional oxygen saturation (rSO2), a marker of hepatic oxygenation reflecting hepato-splanchnic circulation and oxygenation, was monitored. Changes in hepatic rSO2 at the lowest systolic blood pressure (BP) during HD were analyzed to identify associations with clinical factors. Results: Hepatic rSO2 levels were 55.8 ± 15.3% before HD and 53.8 ± 14.9% at the lowest systolic BP; therefore, % changes in hepatic rSO2 were −2.7 ± 11.3%. These values were significantly lower in patients with IDH than in those without IDH (−13.8 ± 9.3% vs 0.4 ± 9.8%, p 2 were independently associated with % changes in systolic BP (standardized coefficient: 0.416) and ultrafiltration rate (−0.206). Furthermore, % changes in mean BP (0.304) were identified as affecting % changes in hepatic rSO2 instead of those in systolic BP. Conclusions: Changes in intradialytic hepatic oxygenation is associated with ultrafiltration rate and changes in systemic BP. Further studies are required to clarify the directionality of the association between changes in hepatic oxygenation and changes in systemic BP during HD.

Background and study aims An important therapeutic aim in ulcerative colitis (UC) is endoscopic remission. Although an endoscopic score with white light imaging (WLI) is mainly used to evaluate endoscopic findings, the usefulness of linked color imaging (LCI) has been reported. We evaluated the relationship between LCI and histopathological findings and attempted to establish a new LCI endoscopic evaluation index for UC. Patients and methods This study was conducted at Kyorin University, Kyoto Prefectural University, and Fukuoka University Chikushi Hospital. Ninety-two patients with a Mayo endoscopic subscore (MES) ≤ 1 who underwent colonoscopy for UC in clinical remission were included. LCI index was defined as redness (R) (Grade 0–2), area of inflammation (A) (Grade 0–3), and lymphoid follicles (L) (Grade 0–3). Histological healing was defined as Geboes score Results In 92 patients, 85 biopsies from the sigmoid colon and 84 biopsies from the rectum (total 169 biopsies) were evaluated. There were 22, 117, and 30 cases of Grades 0, 1, and 2, respectively in LCI index-R; 113, 34, 17, and five cases of Grades 0, 1, 2, and 3, respectively, in LCI index-A; and 124, 27, 14, and four cases of Grades 0, 1, 2, and 3, respectively, in LCI index-L. Histological healing was achieved in 84.0 % of the cases (142 of 169), and there were significant associations with histological healing or non-healing in LCI index-R (P = 0.013) and A (P = 0.0014). Conclusions A new LCI index is useful for predicting histological healing in UC patients with MES ≤ 1 and clinical remission.

Dysphagia is one of the postoperative complications of cervical degenerative disorders. However, few studies have evaluated the pre- and postoperative swallowing function in detail.To analyze pre- and postoperative swallowing dynamics kinetically and investigate factors associated with postoperative dysphagia in patients with cervical degenerative disorders.Retrospective review of prospectively collected data.A total of 41 consecutive patients who underwent an anterior approach (anterior cervical discectomy/corpectomy and fusion (ACDF, ACCF), hybrid surgery (ACDF+ACCF) and total disc replacement) and 44 consecutive patients who underwent a posterior approach (laminoplasty and laminoplasty/laminectomy with fusion).We compared the pre- and postoperative functional oral intake scale (FOIS), dysphagia severity scale (DSS), esophageal dysphagia, anterior/superior hyoid movement, upper esophageal sphincter (UES) opening, pharyngeal transit time, bolus residue scale (BRS), and the number of swallows.Videofluoroscopy was performed on the day before surgery and within two weeks after surgery. Data related to age, gender, disease, surgical procedure, surgical site, operative time, and blood loss were collected from the medical records. Pre- and postoperative data were compared for each item in the anterior and posterior approaches. The odds ratio of dysphagia after an anterior approach was also calculated.In the anterior approach, DSS, FOIS, the anterior and superior hyoid movements, maximum UES opening, BRS, and number of swallows worsened postoperatively (p.05, respectively). In the posterior approach, DSS, FOIS, the anterior hyoid movement, and BRS worsened postoperatively (p.05, respectively). The factors associated with dysphagia were a proximal surgical site above C3 (OR: 14.40, CI: 2.84-73.02), blood loss100 ml (OR: 9.60, CI: 2.06-44.74), an operative time200 min (OR: 8.18, CI: 1.51-44.49), and an extensive surgical field of more than three intervertebral levels (OR: 6.72, CI: 1.50-30.07). The decline in swallowing function after the posterior approach was related to aging (p = .045).Each approach may decrease swallowing function, especially because of the limitation on the anterior hyoid movement. Dysphagia after anterior approaches was associated with the operative site, operative time, and blood loss.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative option for patients with hematological disorders and bone marrow (BM) failure syndromes. Graft-versus-host disease (GVHD) remains a leading cause of morbidity posttransplant. Regulatory T cell (Treg) therapies are efficacious in ameliorating GVHD but limited by variable suppressive capacities and the need for a high therapeutic dose. Here, we sought to expand Treg in vivo by expressing an orthogonal interleukin 2 receptor β (oIL-2Rβ) that would selectively interact with oIL-2 cytokine and not wild-type (WT) IL-2. To test whether the orthogonal system would preferentially drive donor Treg expansion, we used a murine major histocompatibility complex–disparate GVHD model of lethally irradiated BALB/c mice given T cell–depleted BM from C57BL/6 (B6) mice alone or together with B6Foxp3+GFP+ Treg or oIL-2Rβ–transduced Treg at low cell numbers that typically do not control GVHD with WT Treg. On day 2, B6 activated T cells (Tcons) were injected to induce GVHD. Recipients were treated with phosphate-buffered saline (PBS) or oIL-2 daily for 14 days, then 3 times weekly for an additional 14 days. Mice treated with oIL-2Rβ Treg and oIL-2 compared with those treated with PBS had enhanced GVHD survival, in vivo selective expansion of Tregs, and greater suppression of Tcon expansion in secondary lymphoid organs and intestines. Importantly, oIL-2Rβ Treg maintained graft-versus-tumor (GVT) responses in 2 distinct tumor models (A20 and MLL-AF9). These data demonstrate a novel approach to enhance the efficacy of Treg therapy in allo-HSCT using an oIL-2/oIL-2Rβ system that allows for selective in vivo expansion of Treg leading to GVHD protection and GVT maintenance.

Background Tissue-resident memory T (Trm) cells are associated with cytotoxicity not only in viral infection and autoimmune disease pathologies but also in many cancers. Tumour-infiltrating CD103+ Trm cells predominantly comprise CD8 T cells that express cytotoxic activation and immune checkpoint molecules called exhausted markers. This study aimed to investigate the role of Trm in colorectal cancer (CRC) and characterise the cancer-specific Trm. Methods Immunochemical staining with anti-CD8 and anti-CD103 antibodies for resected CRC tissues was used to identify the tumour-infiltrating Trm cells. The Kaplan–Meier estimator was used to evaluate the prognostic significance. Cells immune to CRC were targeted for single-cell RNA-seq analysis to characterise cancer-specific Trm cells in CRC. Results The number of CD103+/CD8+ tumour-infiltrating lymphocytes (TILs) was a favourable prognostic and predictive factor of the overall survival and recurrence-free survival in patients with CRC. Single-cell RNA-seq analysis of 17,257 CRC-infiltrating immune cells revealed a more increased zinc finger protein 683 (ZNF683) expression in cancer Trm cells than in noncancer Trm cells and in high-infiltrating Trm cells than low-infiltrating Trm in cancer, with an upregulated T-cell receptor (TCR)- and interferon-γ (IFN-γ) signalling-related gene expression in ZNF683+ Trm cells. Conclusions The number of CD103+/CD8+ TILs is a prognostic predictive factor in CRC. In addition, we identified the ZNF683 expression as one of the candidate markers of cancer-specific Trm cells. IFN-γ and TCR signalling and ZNF683 expression are involved in Trm cell activation in tumours and are promising targets for cancer immunity regulation.

Factors related to postoperative mechanical failure after long fusion with lower instrumented vertebra (LIV) at L5 have not been well investigated. Elucidating such factors may allow us to perform alternatives to spinopelvic fusion for adult spinal deformity (ASD) cases. We investigated the incidence and risk factors of LIV failure in patients with ASD who underwent surgical treatment of long corrective fusion until the L5 vertebrae.Between 2009 and 2018, 52 patients who underwent corrective fusions to L5 were followed-up for at least one-year. We evaluated the associated patient factors for LIV failure which include loosening of the pedicle screw of LIV, fracture of LIV, distal junctional kyphosis (DJK).The mean age of the participants was 71.2 ± 7.59 (range, 44-84). LIV failure occurred in 20 patients (38.5%), and 6 patients (11.5%) underwent secondary surgery for caudal segments. The mean pelvic incidence (PI) was 52.5 ± 9.8 in the failure group versus 45.3 ± 11.4 in non-failure group (P = 0.02) and pelvic tilt (PT) was 39.1 ± 9.0 versus 32.4 ± 13.0. There were no significant differences in sex, age, body mass index, number of levels fused, and other radiographic data. Logistic regression analysis that included T1 pelvic angle, PT, PI - postoperative LL and PI also identified PI as the only significant determinant of LIV failure (OR = 1.07, P = 0.034). Receiver operating characteristic analysis demonstrated that a PI over 50.0° was associated with LIV failure (sensitivity 63%, specificity 70%, AUC 0.694).LIV failure was frequently observed after long corrective fusion for patients with ASD. High PI was found to be a significant risk factor for the LIV failure.

Funder: United Nations; Id: http://dx.doi.org/10.13039/100004420, The evolution of the development discourse is profoundly political. Despite a range of innovations the situation remains much the same, and has led over time to the dominance of the economic growth model. Whilst academic/ideological vigour, policy relevance and institutional support, together with intellectual independence, are essential; too radical an alternative approach would be dismissed by mainstream opinion, either by design or neglect. To survive and to remain influential, any alternative requires the mainstream to engage with it for political feasibility. The development discourse has thus evolved through a delicate balancing act, acknowledging a need for a cautiously optimistic outlook. By tracing changes in two approaches to development (basic needs and human development) and in two global development goals (millennium development goals and sustainable development goals) through their selection and use of indicators, this article explores both the explicit and the implicit power of the mainstream in the past and present alternatives.