Signal transducer and activator of transcription 3 (STAT3) orchestrates the differentiation of several cell types, including interleukin-17 (IL-17)-releasing Th17 cells. Dysregulation of Th17 cells results in chronic inflammatory responses. Ssu72 is a C-terminal domain phosphatase required for transcriptional regulation. However, the mechanism by which Ssu72 affects STAT3 activation and Th17 cell differentiation is unclear. Here, we found that Ssu72 overexpression suppresses STAT3 activation and Th17 cell responses in vitro. A systemic infusion of Ssu72 attenuates experimental autoimmune arthritis by reducing STAT3 activity and the differentiation of Th17 cells. It also reduces joint destruction, serum immunoglobulin concentrations and osteoclastogenesis but increases the number of marginal zone B cells and B10 cells. These effects are associated with reduced p-STAT3 levels and the suppression of Th17 cell formation in vivo. Based on these data, Ssu72 is related to STAT3 activation and the inflammatory response; and Ssu72 overexpression in T-cell-mediated immunity has potential utility for the treatment of autoimmune arthritis.

In this paper, we reported superior performance of solution-processed top-emission quantum dot light-emitting diodes (TE-QLEDs) with Mg-doped ZnO nanoparticle (NP) electron transport layer (ETL). The Mg-doped ZnO NPs were synthesized by the sol-gel method. Transmission electron microscopy (TEM) analysis of the Mg-doped ZnO NPs with 0 wt%, 5 wt%, 10 wt%, and 15 wt% Mg-doping concentrations revealed average diameters of 5.86 nm, 5.33 nm, 4.52 nm, and 4.37 nm, respectively. The maximum luminance, the current efficiency, and external quantum efficiency (EQE) were 178,561.8 cd/m2, 56.0 cd/A, and 14.43%, respectively. However, for the best performance of TE-QLED without Mg-doping in the ZnO NPs, the maximum luminance was only 101,523.4 cd/m2, the luminous efficiency was 27.8 cd/A, and the EQE was 6.91%. The improvement of the performance is attributed to the suppression of electron transfer by an increase in the energy barrier between the cathode and Mg-doped ZnO NP ETL and the reduction in the Hall mobility of electron with increasing the Mg-doping in the ZnO NPs, resulting in the enhanced charge balance in the quantum dot (QD) emitting layer (EML).

Ankylosing spondylitis (AS) can involve the eye, gastrointestinal system, cardiopulmonary system, skin, kidneys, and spinal and peripheral joints. It is rarely accompanied by immunoglobulin A (IgA) nephropathy. Although IgA is involved in both AS and IgA nephropathy, the relationship between these diseases remains unclear. We detected hematuria and proteinuria in a 32-year-old male patient with ankylosing spondylitis that remained stable for 4 years through treatment with etanercept, a tumor necrosis factor-α (TNF-α) inhibitor, and diagnosed IgA nephropathy through a renal biopsy. IgA nephropathy seems to be less commonly associated with AS disease activity or specific treatment such as TNF-α inhibitor use.

Cyclin-dependent kinase (Cdk) in complex with a corresponding cyclin plays a pivotal role in neurogenic differentiation. In particular, Cdk4 activity acts as a signaling switch to direct human mesenchymal stem cells (MSCs) to neural transdifferentiation. However, the molecular evidence of how Cdk4 activity converts MSCs to neurogenic lineage remains unknown. Here, we found that Cdk4 inhibition in human MSCs enriches the populations of neural stem and progenitor pools rather than differentiated glial and neuronal cell pools. Interestingly, Cdk4 inhibition directly inactivates Smads and subsequently STAT3 signaling by hypophosphorylation, and both Cdk4 and Smads levels are linked during the processes of neural transdifferentiation and differentiation. In summary, our results provide novel molecular evidence in which Cdk4 inhibition leads to directing human MSCs to a multipotent neurogenic fate by inactivating Smads-STAT3 signaling.

Tenofovir disoproxil fumarate (TDF) is thought to cause varying degrees of hypophosphatemia in patients with chronic hepatitis B (CHB). Therefore, we investigated factors that cause hypophosphatemia in patients treated with TDF and methods to increase serum phosphorus concentrations in clinical practice.We completed a retrospective review of patients with CHB treated with TDF initially at

ObjectivesZZCognitive behavioraltherapyandsocialskillstraininghavebeenproposedas a promisingmodalityfortreatmentofpatientswithschizophrenia.Theobjectiveofthisstudywas toevaluatetheeffectivenessofCognitiveBehavioralSocialSkillTraining(CBSST)inpatientswith chronicschizophrenia.MethodsZZTwentysixmiddle-orolder-agedhospitalizedpatientswithschizophreniawereselectedinamentalhospital.Elevenparticipantswererandomlyassignedtoundergotreatment withCBSSTand15participantswereassignedtoreceivetheusualtreatment.CBSSTwasadministeredinasinglegroupover12sessionsforaperiodofweeks,andtheparticipantswere assessedbyblindedratersatbaselineandendpoint,andendoftreatment.ResultsZZComparedtopatientswhoreceivedtheusualtreatment,thosewhoreceivedtreatmentwithCBSSTshowedasignificantreductionofHamiltonRatingScaleforDepressionscore, however,scoresforotherpsychiatricsymptomsdidnotdiffersignificantly.IntermsofQualityof life (QoL) analysis, scores for overall quality of life showed a more significant increase in the CBSSTgroup,comparedwiththegroupofpatientswhoreceivedtheusualtreatment.AccordingtoresultsoftheIndependentLivingSkillSurvey,patientsreceivingCBSSTshowedsignificantlygreaterinvolvementinsocialactivitiesthanpatientsreceivingusualtreatmentgroup.

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The hippo pathway is a critical transcriptional regulator of cell growth, proliferation, and migration in cancer, furthermore,YAP-TEAD complexes act as a major role in the pathway. S-palmitoylation of cysteine residues in TEAD proteins is required for their stability and function in hippo pathway signaling. Recently, it has become manifested that the dysregulation of hippo pathway effectors (MST1/2 and LATS1/2) is involved in oncogenesis. These effectors inactivate translocation of YAP and TAZ into the nucleus. The translocation of YAP/TAZ is responsible for acting as transcriptional coactivators by binding to the transcription factor, TEADs resulting in the transcription of cancer-related genes that drive tumor growth. Since YAP/TAZ are considered to be natively unfolded and can be difficult to handle as a drug target, TEAD is regarded as an excellent therapeutic target for intervention of the hippo pathway. SJP1901 is a small molecule of TEAD inhibitor with potential as drug candidates in malignant mesothelioma and other types of cancer. Based on the results of structure-based drug design, hit compounds were synthesized and their efficacy was evaluated.The compounds effectively inhibited palmitoylation of TEAD proteins and showed remarkable efficacy in reporter gene assay using TEAD responsive element (TRE)-integrated MCF7 with nano molar IC50 concentrations. The excellent anti-tumor effect of SJP1901 was revealed via cell proliferation inhibition assay (nano molar IC50 concentrations) andanalysis of inhibited transcription activity for target genes (CTGF and CYR61) usingmalignant mesothelia cell lines (NCI-H226, NCI-H2052 and MSTO-211H) known to display hippo pathway-dependent cell growth. In addition, these compounds showed lower toxicities in normal cells such as Fa2N4, CCD-18co and WI38 (IC50>10 μM). In conclusion, we obtained potent small molecules which inactivate TEAD proteins by directly inhibiting their palmitoylation. SJP1901 showed outstanding anti-cancer effects through regulating hippo pathway-mediated target genes and lower toxicitiy in normal cells. In vivo efficacy study and research to expand the indications are currently ongoing. Citation Format: Jihyun Um, Janghyun Lee, Kwangwoo Hwang, Sujin Park, Jooyoung Hyun, Dohyeong Lee, Jeongmin Lee, Li-Kyung Kim, Moon Jung Back, Seong Jun Park, Hwan Jung Lim, You-Keun Shin, Hei-Cheul Jeung, Jaewoong Lee, Hyun Tae Kim, Yongbin Park, Hoseok Kwon, Min-Hyo Ki. SJP1901, a small molecule inhibitor targeting hippo pathway by directly inhibiting TEAD palmitoylation in hippo pathway-dependent cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1295.