tbuckley/cabot-search huggingface dataset:
TCR signaling induces STAT3 phosphorylation to promote TH17 cell differentiation
Authors: Zhen Qin, Ruining Wang, Ping Hou, Yuanyuan Zhang, Qianmu Yuan, Ying Wang, Yuedong Yang, Tao Xu
Journal: The Journal of Experimental Medicine (2024)

TH17 differentiation is critically controlled by "signal 3" of cytokines (IL-6/IL-23) through STAT3. However, cytokines alone induced only a moderate level of STAT3 phosphorylation. Surprisingly, TCR stimulation alone induced STAT3 phosphorylation through Lck/Fyn, and synergistically with IL-6/IL-23 induced robust and optimal STAT3 phosphorylation at Y705. Inhibition of Lck/Fyn kinase activity by Srci1 or disrupting the interaction between Lck/Fyn and STAT3 by disease-causing STAT3 mutations selectively impaired TCR stimulation, but not cytokine-induced STAT3 phosphorylation, which consequently abolished TH17 differentiation and converted them to FOXP3+ Treg cells. Srci1 administration or disrupting the interaction between Lck/Fyn and STAT3 significantly ameliorated TH17 cell-mediated EAE disease. These findings uncover an unexpected deterministic role of TCR signaling in fate determination between TH17 and Treg cells through Lck/Fyn-dependent phosphorylation of STAT3, which can be exploited to develop therapeutics selectively against TH17-related autoimmune diseases. Our study thus provides insight into how TCR signaling could integrate with cytokine signal to direct T cell differentiation.
Platinum‐Loaded Cerium Oxide Capable of Repairing Neuronal Homeostasis for Cerebral Ischemia‐Reperfusion Injury Therapy
Authors: Qiang Zhang, Zihao Liu, Bo Li, Liuhua Mu, Kai Sheng, Yijia Xiong, Jiahui Cheng, Jia Zhou, Zhi Xiong, Lingling Zhou, Lixian Jiang, Jianrong Wu, Xiaojun Cai, Yuanyi Zheng, Wenxian Du, Yuehua Li, Yueqi Zhu
Journal: Advanced Healthcare Materials (2024)

Abstract Effective neuroprotective agents are required to prevent neurological damage caused by reactive oxygen species (ROS) generated by cerebral ischemia‐reperfusion injury (CIRI) following an acute ischemic stroke. Herein, it is aimed to develop the neuroprotective agents of cerium oxide loaded with platinum clusters engineered modifications (Pt n ‐CeO 2 ). The density functional theory calculations show that Pt n ‐CeO 2 could effectively scavenge ROS, including hydroxyl radicals (·OH) and superoxide anions (·O 2 − ). In addition, Pt n ‐CeO 2 exhibits the superoxide dismutase‐ and catalase‐like enzyme activities, which is capable of scavenging hydrogen peroxide (H 2 O 2 ). The in vitro studies show that Pt n ‐CeO 2 could adjust the restoration of the mitochondrial metabolism to ROS homeostasis, rebalance cytokines, and feature high biocompatibility. The studies in mice CIRI demonstrate that Pt n ‐CeO 2 could also restore cytokine levels, reduce cysteine aspartate‐specific protease (cleaved Caspase 3) levels, and induce the polarization of microglia to M2‐type macrophages, thus inhibiting the inflammatory responses. As a result, Pt n ‐CeO 2 inhibits the reperfusion‐induced neuronal apoptosis, relieves the infarct volume, reduces the neurological severity score, and improves cognitive function. Overall, these findings suggest that the prominent neuroprotective effect of the engineered Pt n ‐CeO 2 has a significant neuroprotective effect and provides a potential therapeutic alternative for CIRI.
Breast cancer screening awareness among transgender individuals in Bangkok, Thailand
Authors: Sopark Manasnayakorn, Pavinee Annoppornchai, Wasin Laohavinij, Nittaya Phanupak, Ammarin Suwan, Poonpissamai Suwajo
Journal: International Journal of Transgender Health (2024)

Background: Transgender women have higher rates of mortality associated with cancer diagnosis owing to inadequate transgender-specific cancer screening, leading to delayed diagnosis. Gender-affirming hormone therapy, age, and genetics are risk factors for breast cancer in transgender women. For transgender men, the risks were similar to those for cisgender women. However, population-based data on breast cancer screening and awareness among these sex groups are limited.
Recent Advances in Implantable Neural Interfaces for Multimodal Electrical Neuromodulation
Authors: Liu Wang, Shengnan Liu, Wentai Zhao, Jiakun Li, Haoxuan Zeng, Shaoyang Kang, Xing Sheng, Lizhen Wang, Yubo Fan, Lan Yin
Journal: Advanced Healthcare Materials (2024)

Electrical neuromodulation plays a pivotal role in enhancing patient outcomes among individuals suffering from neurological disorders. Implantable neural interfaces are vital components of the electrical neuromodulation system to ensure desirable performance; However, conventional devices are limited to a single function and are constructed with bulky and rigid materials, which often leads to mechanical incompatibility with soft tissue and an inability to adapt to the dynamic and complex 3D structures of biological systems. In addition, current implantable neural interfaces utilized in clinical settings primarily rely on wire-based techniques, which are associated with complications such as increased risk of infection, limited positioning options, and movement restrictions. Here, the state-of-art applications of electrical neuromodulation are presented. Material schemes and device structures that can be employed to develop robust and multifunctional neural interfaces, including flexibility, stretchability, biodegradability, self-healing, self-rolling, or morphing are discussed. Furthermore, multimodal wireless neuromodulation techniques, including optoelectronics, mechano-electrics, magnetoelectrics, inductive coupling, and electrochemically based self-powered devices are reviewed. In the end, future perspectives are given.
IDHwt glioblastomas can be stratified by their transcriptional response to standard treatment, with implications for targeted therapy
Authors: Georgette Tanner, Rhiannon Barrow, Shoaib Ajaib, Muna Al-Jabri, Nazia Ahmed, Steven Pollock, Martina Finetti, Nora Rippaus, Alexander F. Bruns, Khaja Syed, James A. Poulter, Laura Matthews, Thomas Hughes, Erica Wilson, Colin Johnson, Frederick S. Varn, Anke Brüning-Richardson, Catherine Hogg, Alastair Droop, Arief Gusnanto, Matthew A. Care, Luisa Cutillo, David R. Westhead, Susan C. Short, Michael D. Jenkinson, Andrew Brodbelt, Aruna Chakrabarty, Azzam Ismail, Roel G. W. Verhaak, Lucy F. Stead
Journal: Genome biology (2024)

Glioblastoma (GBM) brain tumors lacking IDH1 mutations (IDHwt) have the worst prognosis of all brain neoplasms. Patients receive surgery and chemoradiotherapy but tumors almost always fatally recur.
Protect our environment from information overload
Authors: Janusz A. Hołyst, Philipp Mayr, Michael Thelwall, Ingo Frommholz, Shlomo Havlin, Alon Sela, Yoed N. Kenett, Denis Helic, Aljoša Rehar, Sebastijan R. Maček, Przemysław Kazienko, Tomasz Kajdanowicz, Przemysław Biecek, Boleslaw K. Szymanski, Julian Sienkiewicz
Journal: Nature Human Behaviour (2024)
The development of non‐resorbable bone allografts: Biological background and clinical perspectives
Authors: Richard J. Miron, Masako Fujioka‐Kobayashi, Michael A. Pikos, Toshiaki Nakamura, Takatomo Imafuji, Yufeng Zhang, Yukiya Shinohara, Anton Sculean, Yoshinori Shirakata
Journal: Periodontology 2000 (2024)

Abstract Bone grafts are typically categorized into four categories: autografts, allografts, xenografts, and synthetic alloplasts. While it was originally thought that all bone grafts should be slowly resorbed and replaced with native bone over time, accumulating evidence has in fact suggested that the use of nonresorbable xenografts is favored for certain clinical indications. Thus, many clinicians take advantage of the nonresorbable properties/features of xenografts for various clinical indications, such as contour augmentation, sinus grafting, and guided bone regeneration, which are often combined with allografts (e.g., human freeze‐dried bone allografts [FDBAs] and human demineralized freeze‐dried bone allografts [DFDBAs]). Thus, many clinicians have advocated different 50/50 or 70/30 ratios of allograft/xenograft combination approaches for various grafting procedures. Interestingly, many clinicians believe that one of the main reasons for the nonresorbability or low substitution rates of xenografts has to do with their foreign animal origin. Recent research has indicated that the sintering technique and heating conducted during their processing changes the dissolution rate of hydroxyapatite, leading to a state in which osteoclasts are no longer able to resorb (dissolve) the sintered bone. While many clinicians often combine nonresorbable xenografts with the bone‐inducing properties of allografts for a variety of bone augmentation procedures, clinicians are forced to use two separate products owing to their origins (the FDA/CE does not allow the mixture of allografts with xenografts within the same dish/bottle). This has led to significant progress in understanding the dissolution rates of xenografts at various sintering temperature changes, which has since led to the breakthrough development of nonresorbable bone allografts sintered at similar temperatures to nonresorbable xenografts. The advantage of the nonresorbable bone allograft is that they can now be combined with standard allografts to create a single mixture combining the advantages of both allografts and xenografts while allowing the purchase and use of a single product. This review article presents the concept with evidence derived from a 52‐week monkey study that demonstrated little to no resorption along with in vitro data supporting this novel technology as a “next‐generation” biomaterial with optimized bone grafting material properties.
Integrated Stress Response Potentiates Ponatinib-Induced Cardiotoxicity
Authors: Gege Yan, Zhenbo Han, Youjeong Kwon, Jordan Jousma, Sarath Babu Nukala, Benjamin L. Prosser, Xiaoping Du, Sandra Pinho, Sang-Bing Ong, Won Hee Lee, Sang-Ging Ong
Journal: Circulation Research (2024)

Mitochondrial dysfunction is a primary driver of cardiac contractile failure; yet, the cross talk between mitochondrial energetics and signaling regulation remains obscure. Ponatinib, a tyrosine kinase inhibitor used to treat chronic myeloid leukemia, is among the most cardiotoxic tyrosine kinase inhibitors and causes mitochondrial dysfunction. Whether ponatinib-induced mitochondrial dysfunction triggers the integrated stress response (ISR) to induce ponatinib-induced cardiotoxicity remains to be determined.
ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction
Authors: Shiqiang Xu, Qilian Ma, Junwen Shen, Ningning Li, Shan Sun, Nana Wang, Yang Chen, Chunsheng Dong, Kin Yip Tam, Jochen H.M. Prehn, Hongfeng Wang, Zheng Ying
Journal: Acta Pharmaceutica Sinica B (2024)

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two neurodegenerative disorders. The GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72 (C9orf72) is the most genetic cause of both ALS and FTD. According to the previous studies, GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation, which produces dipeptide repeat (DPR) proteins. Although there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD, whether these DPRs can affect autophagy remains unclear. In the present study, we find that poly-GR and poly-PR, two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies, strongly inhibit starvation-induced autophagy. Moreover, our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation, therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in cells. Importantly, our study not only highlights the role of C9orf72 DPR in autophagy dysfunction, but also provides novel insight that pharmacological intervention of autophagy using SW063058, a small molecule compound that can disrupt the interaction between BECN1 and BCL2, may reduce C9orf72 DPR-induced neurotoxicity.
Which trial do we need? Empiric Glycopeptides plus clindamycin versus Oxazolidinones for suspected toxic shock and necrotizing soft tissue infections
Authors: Joshua Osowicki, Fergus Hamilton, Todd C. Lee, Michael Marks, Erin K. McCreary, Emily G. McDonald, Jonathan H. Ryder, Steven Y.C. Tong
Journal: Clinical Microbiology and Infection (2024)
Antimicrobial Guanidinylate Polycarbonates Show Oral In Vivo Efficacy Against <i>Clostridioides Difficile</i>
Authors: Menglin Xue, Soumyadeep Chakraborty, Ruixuan Gao, Shaohui Wang, Meng Gu, Ning Shen, Lulu Wei, Chuanhai Cao, Xingmin Sun, Jianfeng Cai
Journal: Advanced Healthcare Materials (2024)

The emerging antibiotic resistance has been named by the World Health Organization (WHO) as one of the top 10 threats to public health. Notably, methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecalis (VREF) are designated as serious threats, whereas Clostridioides difficile (C. difficile) is recognized as one of the most urgent threats to human health and unmet medical need. Herein, they report the design and application of novel biodegradable polymers - the lipidated antimicrobial guanidinylate polycarbonates. These polymers showed potent antimicrobial activity against a panel of bacteria with fast-killing kinetics and low resistance development tendency, mainly due to their bacterial membrane disruption mechanism. More importantly, the optimal polymer showed excellent antibacterial activity against C. difficile infection (CDI) in vivo via oral administration. In addition, compared with vancomycin, the polymer demonstrated a much-prolonged therapeutic effect and virtually diminished recurrence rate of CDI. The convenient synthesis, easy scale-up, low cost, as well as biodegradability of this class of polycarbonates, together with their in vitro broad-spectrum antimicrobial activity and orally in vivo efficacy against CDI, suggest the great potential of lipidated guandinylate polycarbonates as a new class of antibacterial biomaterials to treat CDI and combat emerging antibiotic resistance.
Issue Information
Authors: Amanda Hargrove, Sandip Bharate, Daniel Harki, Laura Mercolini, Jun Wang, Minyong Li, Nitesh Bhardwaj, Amjad Ali, Marco Alves, Wilfred Armarego, Renren Bai, Matt Bogyo, Amanda Bryant-Friedrich, Vincenzo Calderone, Yihua Chen, Erik De Clercq, Francesco Epifano, Marco Falasca, Haian Fu, Gunda Georg, Junming Guo, Kenneth Jacobson, Zifu Li, Philip Low, Christian Melander, Kunal Nepali, Salvatore Nesci, Beatrice Ranieri, Webster Santos, Daniel Crespo, Teruna Siahaan, Claudiu Supuran, Binghe Wang, Erxi Wu, Bin Yu, Jian Zhang, Jinwei Zhang
Journal: Medicinal Research Reviews (2024)

Aims and Scope:The journal publishes timely critical reviews of topics related to medicinal research, broadly defined, to which the authors have made significant contributions.Appropriate topics include, but are not limited to, the underlying pathophysiology of important diseases and disease vectors; therapeutic approaches to the treatment of various diseases; the properties of molecular targets for therapeutic agents; important new methodologies facilitating the search for therapies; genomics and proteomics; structure-activity correlations of drug series; the development of new imaging and diagnostic tools; drug metabolism; drug delivery; and chemical, pharmacological, pharmacokinetic, pharmacodynamic, and clinical characteristics of important drugs.Articles are mainly solicited by the editors; however, voluntary contributions are also encouraged.In the latter case, potential authors are asked to contact the Editor-in-Chief with an outline before beginning to write in order to avoid duplication of effort and to ensure suitability of the topic and the level of coverage.
All‐in‐One Self‐Powered Microneedle Device for Accelerating Infected Diabetic Wound Repair
Authors: Weikun Li, Zonghao Liu, Xin Tan, Ning Yang, Yanling Liang, Diyi Feng, Han Li, Renqiang Yuan, Qianli Zhang, Ling Liu, Liqin Ge
Journal: Advanced Healthcare Materials (2024)

Abstract Diabetic wound healing remains a significant clinical challenge due to the complex microenvironment and attenuated endogenous electric field. Herein, a novel all‐in‐one self‐powered microneedle device (termed TZ@mMN‐TENG) is developed by combining the multifunctional microneedle carried tannin@ZnO microparticles (TZ@mMN) with the self‐powered triboelectric nanogenerator (TENG). In addition to the delivery of tannin and Zn 2+ , TZ@mMN also effectively conducts electrical stimulation (ES) to infected diabetic wounds. As a self‐powered device, the TENG can convert biomechanical motion into exogenous ES to accelerate the infected diabetic wound healing. In vitro experiment demonstrated that TZ@mMN shows excellent conductive, high antioxidant ability, and effective antibacterial properties against both Staphylococcus aureus and Escherichia coli (&gt;99% antibacterial rates). Besides, the TZ@mMN‐TENG can effectively promote cell proliferation and migration. In the diabetic rat full‐thickness skin wound model infected with Staphylococcus aureus , the TZ@mMN‐TENG can eliminate bacteria, accelerate epidermal growth (regenerative epidermis: ≈303.3 ± 19.1 µm), enhance collagen deposition, inhibit inflammation (lower TNF‐α and IL‐6 expression), and promote angiogenesis (higher CD31 and VEGF expression) to accelerate infected wound repair. Overall, the TZ@mMN‐TENG provides a promising strategy for clinical application in diabetic wound repair.
Cognitive Outcomes After Antidepressant Pharmacotherapy for Late-Life Depression: A Systematic Review and Meta-Analysis
Authors: Nicholas J. Ainsworth, Tulip Marawi, Marta M. Maslej, Daniel M. Blumberger, Mary Pat McAndrews, Argyrios Perivolaris, Bruce G. Pollock, Tarek K. Rajji, Benoit H. Mulsant
Journal: American Journal of Psychiatry (2024)

The authors evaluated whether treatment of late-life depression (LLD) with antidepressants leads to changes in cognitive function.
Intergenerational Effects of the Fast Track Intervention on Next-Generation Child Outcomes: A Preregistered Randomized Clinical Trial
Authors: W. Andrew Rothenberg, Jennifer E. Lansford, Jennifer W. Godwin, Kenneth A. Dodge, William E. Copeland, Candice L. Odgers, Robert J. McMahon, Anna Rybinska
Journal: American Journal of Psychiatry (2024)

The authors sought to determine whether the Fast Track mental health intervention delivered to individuals in childhood decreased mental health problems and the need for health services among the children of these individuals.
Treatment Response Prediction in Major Depressive Disorder Using Multimodal MRI and Clinical Data: Secondary Analysis of a Randomized Clinical Trial
Authors: Maarten G. Poirot, Henricus G. Ruhe, Henk-Jan M.M. Mutsaerts, Ivan I. Maximov, Inge R. Groote, Atle Bjørnerud, Henk A. Marquering, Liesbeth Reneman, Matthan W.A. Caan
Journal: American Journal of Psychiatry (2024)

Response to antidepressant treatment in major depressive disorder varies substantially between individuals, which lengthens the process of finding effective treatment. The authors sought to determine whether a multimodal machine learning approach could predict early sertraline response in patients with major depressive disorder. They assessed the predictive contribution of MR neuroimaging and clinical assessments at baseline and after 1 week of treatment.
A Triple‐Responsive Polymeric Prodrug Nanoplatform with Extracellular ROS Consumption and Intracellular H<sub>2</sub>O<sub>2</sub> Self‐Generation for Imaging‐Guided Tumor Chemo‐Ferroptosis‐Immunotherapy
Authors: Yongjuan Li, Yongjian Cao, Kunru Ma, Rong Ma, Mengzhe Zhang, Yichen Guo, Haiwei Song, Nannan Sun, Zhenzhong Zhang, Weijing Yang
Journal: Advanced Healthcare Materials (2024)

Abstract High reactive oxygen species (ROS) levels in tumor microenvironment (TME) impair both immunogenic cell death (ICD) efficacy and T cell activity. Furthermore, tumor escapes immunosurveillance via programmed death‐1/programmed death ligand‐1 (PD‐L1) signal, and the insufficient intracellular hydrogen peroxide weakens ferroptosis efficacy. To tackle the above issues, a glutathione (GSH)/ROS/pH triple‐responsive prodrug nanomedicine that encapsulates Fe 2 O 3 nanoparticle via electrostatic interaction is constructed for magnetic resonance imaging (MRI)‐guided multi‐mode theranostics with chemotherapy/ferroptosis/immunotherapy. The diselenide bond consumes ROS in TME to increase T cells and ICD efficacy, the cleavage of which facilitates PD‐L1 antagonist D peptide release to block immune checkpoint. After intracellular internalization, Fe 2 O 3 nanoparticle is released in the acidic endosome for MRI simultaneously with lipid peroxides generation for tumor ferroptosis. Doxorubicin is cleaved from polymers in the condition of high intracellular GSH level accompanied by tumor ICD, which simultaneously potentiates ferroptosis by NADPH oxidase mediated H 2 O 2 self‐generation. In vivo results indicate that the nanoplatform strengthens tumor ICD, induces cytotoxic T lymphocytes proliferation, inhibits 4T1 tumor regression and metastasis, and prolongs survival median. In all, a new strategy is proposed in strengthening ICD and T cells activity cascade with ferroptosis as well as immune checkpoint blockade for effective tumor immunotherapy.
Impact of vutrisiran on exploratory cardiac parameters in hereditary transthyretin‐mediated amyloidosis with polyneuropathy
Authors: Pablo Garcia‐Pavia, Martha Grogan, Parag Kale, John L. Berk, Mathew S. Maurer, Isabel Conceição, Marcelo Di Carli, Scott D. Solomon, Chongshu Chen, Elena Yureneva, John Vest, Julian D. Gillmore
Journal: European Journal of Heart Failure (2024)

HELIOS-A was a Phase 3, open-label study of vutrisiran, an RNA interference therapeutic, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. This analysis evaluated vutrisiran's impact on exploratory cardiac endpoints in HELIOS-A patients.