Search

The activation of yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ) has been implicated in both regeneration and tumorigenesis, thus representing a double-edged sword in tissue homeostasis. However, how the activity of YAP1/TAZ is regulated or what leads to its dysregulation in these processes remains unknown. To explore the upstream stimuli modulating the cellular activity of YAP1/TAZ, we developed a highly sensitive YAP1/TAZ/TEAD-responsive DNA element (YRE) and incorporated it into a lentivirus-based reporter cell system to allow for sensitive and specific monitoring of the endogenous activity of YAP1/TAZ in terms of luciferase activity in vitro and Venus fluorescence in vivo. Furthermore, by replacing YRE with TCF- and NF-κB-binding DNA elements, we demonstrated the applicability of this reporter system to other pathways such as Wnt/β-catenin/TCF- and IL-1β/NF-κB-mediated signaling, respectively. The practicality of this system was evaluated by performing cell-based reporter screening of a chemical compound library consisting of 364 known inhibitors, using reporter-introduced cells capable of quantifying YAP1/TAZ- and β-catenin-mediated transcription activities, which led to the identification of multiple inhibitors, including previously known as well as novel modulators of these signaling pathways. We further confirmed that novel YAP1/TAZ modulators, such as potassium ionophores, Janus kinase inhibitors, platelet-derived growth factor receptor inhibitors, and genotoxic stress inducers, alter the protein level or phosphorylation of endogenous YAP1/TAZ and the expression of their target genes. Thus, this reporter system provides a powerful tool to monitor endogenous signaling activities of interest (even in living cells) and search for modulators in various cellular contexts., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Molecular one-dimensional (1D) electron systems have attracted much attention due to their unique electronic state, physical and chemical properties derived from high-aspect-ratio structures. Among 1D materials, mixed-valence halogen-bridged transition-metal chain complexes (MX-chains) based on coordination assemblies are currently of particular interest because their electronic properties, such as mixed-valence state and band gap, can be controlled by substituting components and varying configurations. In particular, chemistry has recently noted that dimensionally extending MX-chains through organic rung ligands can introduce and modulate electronic coupling of metal atoms between chains, i.e., interchain interactions. In this review, for the first time, we highlight the recent progress on MX systems from the viewpoint of dimensionally extending from 1D chain to ladder and nanotube, mainly involving structural design and electronic properties. Overall, dimensional extension can not only tune the electronic properties of MX-chain, but also build the unique platform for studying transport dynamics in confined space, such as proton conduction. Based on these features, we envision that the MX-chain systems provide valuable insights into deep understanding of 1D electron systems, as well as the potential applications such as nanoelectronics., (© 2024 Wiley‐VCH GmbH.)

Desmoplakin (Dsp) is a component of desmosomal cell-cell junctions that interacts with the cadherin complex and cytoskeletal intermediate filaments. In addition to its function as an adhesion component, Dsp is involved in various biological processes, such as gene expression, differentiation, and migration. Dsp is specifically expressed in the hippocampal dentate gyrus (DG) in the central nervous system. However, it is unclear how Dsp impacts hippocampal function and its related behaviors. Using an adeno-associated virus knockdown system in mice, we provide evidence that Dsp in the DG maintains hippocampal functions, including neuronal activity and adult neurogenesis, and contributes to anxiolytic-like effects. Dsp protein is mostly localized in mature granule cells in the adult DG. Dsp knockdown in the DG resulted in a lowered expression of an activity-dependent transcription factor FosB, and an increased expression of mature neuronal markers, such as calbindin. In addition, the suppression of Dsp decreases serotonin responsiveness at the DG output mossy fiber synapses and alters adult neurogenic processes in the subgranular zone of the DG. Moreover, DG-specific Dsp knockdown mice showed an increase in anxiety-like behaviors. Taken together, this research uncovers an unexplored function for Dsp in the central nervous system and suggests that Dsp in the DG may function as a regulator to maintain proper neuronal activation and adult neurogenesis, and contribute to the adaptation of emotion-related behavior., 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 Otsubo, Sakashita, Nishimoto, Sato, Tsutsui, Kobayashi, Suzuki and Segi-Nishida.)

Objectives: Predicting the prognosis of lung cancer is crucial for providing optimal medical care. However, a method to accurately predict the overall prognosis in patients with stage IV lung cancer, even with the use of machine learning, has not been established. Moreover, the inter-institutional generalizability of such algorithms remains unexplored. This study aimed to establish machine learning-based algorithms with inter-institutional generalizability to predict prognosis., Materials and Methods: This multicenter, retrospective, hospital-based cohort study included consecutive patients with stage IV lung cancer who were randomly categorized into the training and independent test cohorts with a 2:1 ratio, respectively. The primary metric to assess algorithm performance was the area under the receiver operating characteristic curve in the independent test cohort. To assess the inter-institutional generalizability of the algorithms, we investigated their ability to predict patient outcomes in the remaining facility after being trained using data from 15 other facilities., Results: Overall, 6,751 patients (median age, 70 years) were enrolled, and 1,515 (22 %) showed mutated epidermal growth factor receptor expression. The median overall survival was 16.6 (95 % confidence interval, 15.9-17.5) months. Algorithm performance metrics in the test cohort showed that the areas under the curves were 0.90 (95 % confidence interval, 0.88-0.91), 0.85 (0.84-0.87), 0.83 (0.81-0.85), and 0.85 (0.82-0.87) at 180, 360, 720, and 1,080 predicted survival days, respectively. The performance test of 16 algorithms for investigating inter-institutional generalizability showed median areas under the curves of 0.87 (range, 0.84-0.92), 0.84 (0.78-0.88), 0.84 (0.76-0.89), and 0.84 (0.75-0.90) at 180, 360, 720, and 1,080 days, respectively., Conclusion: This study developed machine learning algorithms that could accurately predict the prognosis in patients with stage IV lung cancer with high inter-institutional generalizability. This can enhance the accuracy of prognosis prediction and support informed and shared decision-making in clinical settings., 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: Daichi Fujimoto reported receiving grants and personal fees from AstraZeneca KK and Boehringer Ingelheim Japan Inc. and personal fees from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., MSD KK, Eli Lilly Japan K.K., Kyowa Kirin, Daiichi Sankyo, and Novartis Pharma KK outside the submitted work. Hidetoshi Hayashi reported receiving grants from PAREXEL International Corp., Daiichi Sankyo Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., SYNEOS HEALTH CLINICAL K.K., Covance Japan Inc., Sanofi K.K., Novartis Pharma K.K., Bristol Myers Squibb Company, Janssen Pharmaceutical K.K., Eisai Co., Ltd., Japan Clinical Research Operations, AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Sysmex Corporation, Takeda Pharmaceutical Co., Ltd., IQVIA Services JAPAN K.K., GlaxoSmithKline K.K., EPS Corporation, Medical Research Support, PRA Health Science, Inc., Eisai., Inc., Nippon Boehringer Ingelheim Co., Ltd., and PPD-SNBL K.K. and personal fees from AstraZeneca K.K., Bristol Myers Squibb Company, Amgen, Inc., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Ono Pharmaceutical Co., Ltd., and Pfizer Japan Inc outside the submitted work. Yukihiro Toi reported receiving personal fees from Bristol-Myers Squibb Company, Ono Pharmaceutical Co., Ltd., MSD K.K., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Pfizer, Inc., and Kyowa Kirin Co., Ltd., outside the submitted work. Toshihide Yokoyama reported receiving personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Pfizer Japan Inc, Bristol-Myers Squibb Co., Ltd., Ono Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Nippon Kayaku Co., Ltd., MSD, Novartis, and Merck Biopharma Co., Ltd. outside the submitted work. Terufumi Kato reported receiving grants from Abbvie, Amgen, AstraZeneca, BeiGene, BluePrint, Chugai, Daiichi-Sankyo, Eli Lilly, Haihe, Merck KGaA, MSD, Novartis, Pfizer, Regeneron, Takeda, and TurningPoint and personal fees from Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Chugai, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck KGaA, MSD, Novartis, Ono, Pfizer, Taiho, and Takeda outside the submitted work, and his wife is an employee of Eli Lilly. Teppei Yamaguchi reported receiving personal fees from Ono Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Taiho Pharmaceutical, AstraZeneca, MSD, Bristol-Meyers Squibb, and Novartis outside the submitted work. Kaoru Tanaka reported receiving personal fees from AstraZeneca, Merck Biopharma, Eisai, Bristol-Myers Squibb, Ono Pharmaceutical, MSD, Chugai Pharmaceutical, Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical, and Novartis Pharma outside the submitted work. Satoru Miura reported receiving personal fees from AstraZeneca KK, Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., MSD K.K., Boehringer Ingelheim Japan Inc, Eli Lilly Japan K.K., Novartis Pharma K.K., Pfizer, Kyowa Hakko Kirin, Daiichi Sankyo, Abbive, Nippon Kayaku, AMGEN, Merck, and Takeda Pharmaceutical Co., Ltd. outside the submitted work. Motohiro Tamiya reported receiving personal fees from Pfizer, Chugai Pharmaceutical, Ono Pharmaceutical, MSD, Boehringer Ingelheim, AstraZeneca, Taiho Pharmaceutical, Eli Lilly, Bristol-Myers Squibb, and Amgen outside the submitted work. Motoko Tachihara reported receiving grants and personal fees from AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., and Eli Lilly Japan Co., Ltd., and personal fees from Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., MSD K.K., Novartis pharmaceuticals K.K., Takeda Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Daiichi Sankyo, Pfizer Japan, Inc., and Janssen Pharmaceutical K.K. Takehito Shukuya reported receiving grants and personal fees from AstraZeneca, Chugai Pharmaceutical, Boehringer Ingelheim, Novartis, and MSD and personal fees from Taiho Pharma, Daiichi-Sankyo, Ono Pharmaceutical, Bristol-Myers Squibb, Nippon Kayaku, Pfizer, Takeda Pharmaceutical Co., Ltd., and Eli Lilly outside the submitted work. Yuko Tsuchiya-Kawano reported receiving personal fees from Bristol-Myers Squibb, Taiho Pharmaceutical, Chugai Pharmaceutical, AstraZeneca, Kyowa Hakko Kirin, MSD, and Ono Pharmaceutical outside the submitted work. Yuki Sato reported receiving personal fees from AstraZeneca, MSD, Novartis, Chugai Pharmaceutical, Ono Pharmaceutical, Pfizer, Taiho Pharmaceutical, Nippon Kayaku, Bristol Myers Squibb, Eli Lilly, Takeda Pharmaceutical Co., Ltd., Kyowa Kirin, and Boehringer Ingelheim outside the submitted work. Satoshi Ikeda reported receiving personal fees from AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, Boehringer Ingelheim, Eli Lilly, Takeda Pharmaceutical Co., Ltd., Daiichi-Sankyo, and Pfizer outside the submitted work. Shinya Sakata reported receiving personal fees from AstraZeneca, Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical, and Takeda Pharmaceutical outside the submitted work. Takeshi Masuda reported receiving personal fees from MSD K.K., Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb Co., Ltd., and Kyowa Kirin outside the submitted work. Isamu Okamoto reported receiving personal fees from Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca Plc., Eli Lilly Japan K.K., Takeda Pharmaceutical Co., Ltd., and Novartis Pharma K.K. outside the submitted work. Nobuyuki Yamamoto reported receiving grants from AstraZeneca K.K., MSD K.K., Amgen Astellas BioPharma, Eisai Co., Ltd., Sanofi K.K., Chugai Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Novartis Pharma K.K., Janssen Pharmaceutical K.K., Amgen K.K., Taiho Pharmaceutical Co., Ltd., Toppan USA, Inc., Nippon Boehringer Ingelheim Co., Ltd., and Daiichi Sankyo Co., Ltd. and personal fees from MSD K.K., Amgen K.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca K.K., Ono Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., and Merck Biopharma Co., Ltd., outside the submitted work. The remaining authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Advances in minimally invasive surgery and drainage systems have caused earlier chest-tube-removal. This retrospective study aimed to assess the safety of early chest tube removal using the institution's new criteria 6 hours after thoracic surgery., Methods: Elective thoracic surgery patients from 2017 to 2023 were reviewed for meeting or not meeting the newer institutional requirement for early chest tube removal; (I) no air leak detected under the digital drainage device observation; (II) no fluid drainage of ≥100 mL/h; (III) no ≥3 combined risks [male, chronic obstructive pulmonary disease (COPD), body mass index (BMI) of <18.5 kg/m 2 , severe pleural adhesion, upper lobe lobectomy, or left upper division segmentectomy]. The incidence of adverse events, including chest tube replacement, subcutaneous tube placement, and postoperative thoracentesis, were investigated for 1 month postoperatively. Perioperative outcomes and factors involved in conventional chest tube removal were also assessed., Results: Of the 942 patient charts reviewed, 244 (25.9%) met the criteria for chest tube removal within 6 hours postoperatively. This patient group did not experience adverse events. They also demonstrated shorter postoperative hospital stay (4 vs. 6 days, P<0.001), and lesser postoperative complications (7.4% vs. 25.6%, P<0.001) compared to those for whom early chest tube removal was not done. A correlation with thoracotomy, COPD, and steroid and/or immunosuppressant use was observed for patients in the conventional chest tube removal group., Conclusions: Early chest tube removal after 6 postoperative hours was deemed safe for a selected group of patients who met the criteria for early chest tube removal. This study would support the potential expansion of our early removal criteria., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1905/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Tracheomediastinal fistula is a rare but life-threatening complication of cancer. We report a case of tracheomediastinal fistula induced by concurrent chemoradiotherapy in limited stage small cell lung cancer. Despite the treatment response, the metastatic paratracheal lymph node increased gradually during concurrent chemoradiotherapy, resulting in the occurrence of tracheomediastinal fistula and mediastinitis. Without any surgical intervention, the patient achieved successful recovery from mediastinitis through antibiotic treatment, although the tracheomediastinal fistula remained open. In this report, we also review previous studies of tracheomediastinal and bronchomediastinal fistulas and summarize the clinical features., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Ladder systems situated in the dimensional crossover region have attracted much attention because their electronic states and physical properties depend strongly on the electronic correlations among the constituent legs. Generally, two-/three-legged transition metal-oxide ladder compounds are studied as representative ladder systems, but two-/three-dimensional (2D/3D) extensions based on such ladder systems with a few numbers of legs are difficult because of the extreme synthesis conditions. Here, for the first time, we report the successful creation of a 3D extended two-legged ladder compound, [Pt(en)(dpye)I] 2 (NO 3 ) 4  ⋅ 2H 2 O (en=ethylenediamine; dpye=1,2-Di(4-pyridyl)ethane), which is obtained by simple oxidative polymerization of a small Pt macrocyclic complex using elemental I 2 . The unique 3D extended lattice consists of 1D mixed-valence halogen-bridged metal chains (⋅⋅⋅Pt-I-Pt-I⋅⋅⋅) and helically arranged macrocyclic units as the constituent legs and rungs, as confirmed by single-crystal X-ray diffraction. Diffuse X-ray scattering analyses and optical measurements revealed that the out-of-phase mixed-valence Pt 2+ /Pt 4+ arrangement arises from the weak interchain correlation among adjacent legs. In addition, this compound shows an increase in proton conductivity by a factor of up to 1000, depending on humidity., (© 2024 Wiley‐VCH GmbH.)

Background: Early chest tube removal should be considered to enhance recovery after surgery. The current study aimed to provide a predictive algorithm for air leak episodes (ALE) and to create a knowledge base for early chest tube removal., Methods: This retrospective study enrolled patients who underwent thoracoscopic anatomical pulmonary resections in our unit. We defined ALE as any airflow ≥ 10 mL/min recorded in the follow-up charts based on the digital thoracic drainage device. Multivariate regression analysis was used to control for preoperative and intraoperative confounding factors. The ALE prediction algorithm was constructed by combining an additive ALE risk-scoring system using the coefficients of the significant predictive factors with the intraoperative water-sealing test., Results: In 485 consecutive thoracoscopic major pulmonary resections, ALE developed in 209 (43%) patients. Statistically significant ALE-associated preoperative factors included male sex, lower body mass index, radiologically evident emphysema, lobectomy, and upper lobe surgery. Significant ALE-associated intraoperative factors were incomplete fissure and pleural adhesion. The ALE risk scoring demonstrated an average area under the receiver operating characteristic curve of 0.72 in the fivefold cross-validation test. The ALE prediction algorithm correctly predicted ALE-absent patients at a negative predictive value of 80%., Conclusions: The algorithm may promote the optimization of the chest tube-dwelling duration by identifying potential ALE-absent patients for accelerated tube removal., (© 2024. The Author(s).)

We report on the synthesis and selective adsorption property of a novel threefold interpenetrated Zr-based metal-organic framework (MOF), [Zr 12 O 8 (OH) 8 (HCOO) 15 (BPT) 3 ] (BPT 3- = [1,1'-biphenyl]-3,4',5-tricarboxylate) (abbreviated as Zr-BPT). This MOF shows a high tolerance to acidic conditions and has permanent pores, the size of which (approx. <5.6 Å) is the smallest ever reported among porous Zr-based MOFs with high acid tolerance. Zr-BPT selectively adsorbs aryl acids due to its strong affinity for them and exhibits separation ability, even between strong acid molecules, such as sulfonic and phosphonic acids. This is the first demonstration of a MOF exhibiting selective adsorption and separation ability for strong acids., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The treatment of interstitial lung diseases, including idiopathic pulmonary fibrosis (IPF), remains challenging as current available antifibrotic agents are not effective in halting disease progression. Connective tissue growth factor (CTGF), also known as cellular communication factor 2 (CCN2), is a member of the CCN family of proteins that regulates cell signaling through cell surface receptors such as integrins, the activity of cytokines/growth factors, and the turnover of extracellular matrix (ECM) proteins. Accumulating evidence indicates that CTGF plays a crucial role in promoting lung fibrosis through multiple processes, including inducing transdifferentiation of fibroblasts to myofibroblasts, epithelial-mesenchymal transition (EMT), and cooperating with other fibrotic mediators such as TGF-β. Increased expression of CTGF has been observed in fibrotic lungs and inhibiting CTGF signaling has been shown to suppress lung fibrosis in several animal models. Thus, the CTGF signaling pathway is emerging as a potential therapeutic target in IPF and other pulmonary fibrotic conditions. This review provides a comprehensive overview of the current evidence on the pathogenic role of CTGF in pulmonary fibrosis and discusses the current therapeutic agents targeting CTGF using a systematic review approach., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)