bluuebunny/crossref_metadata_2025_split huggingface dataset:
Eltrombopag directly activates BAK and induces apoptosis
Authors: Chen Meng , Hu Lei , Bao Xuyuan , Ye Kaiqin , Li Yunjian , Zhang Zhiyong , Kaufmann Scott H. , Xiao Jun , Dai Haiming 
Published: July 2023

AbstractSmall molecule direct BAK activators can potentially be used for the development of anti-cancer drugs or as tools to study BAK activation. The thrombopoietin receptor agonist eltrombopag (Eltro) inhibits BAX activation and BAX-mediated apoptosis. Here we report that, in contrast to its function as a BAX inhibitor, Eltro directly binds BAK but induces its activation in vitro. Moreover, Eltro induces or sensitizes BAK-dependent cell death in mouse embryonic fibroblasts (MEFs) and Jurkat cells. Chemical shift perturbation analysis by NMR indicates that Eltro binds to the BAK α4/α6/α7 groove to initiate BAK activation. Further molecular docking by HADDOCK suggests that several BAK residues, including R156, F157, and H164, play an important role in the interaction with Eltro. The introduction of an R156E mutation in the BAK α4/α6/α7 groove not only decreases Eltro binding and Eltro-induced BAK activation in vitro but also diminishes Eltro-induced apoptosis. Thus, our data suggest that Eltro directly induces BAK activation and BAK-dependent apoptosis, providing a starting point for the future development of more potent and selective direct BAK activators.
Tim-3 protects against cisplatin nephrotoxicity by inhibiting NF-κB-mediated inflammation
Authors: Li Peiyao , Li Xuemiao , Wu Wenbin , Hou Mengjia , Yin Guanyi , Wang Zhonghang , Du Ziyu , Ma Yuanfang , Lou Qiang , Wei Yinxiang 
Published: July 2023

AbstractThe impact of Tim-3 (T cell immunoglobulin and mucin domain-containing protein 3) on cisplatin-induced acute kidney injury was investigated in this study. Cisplatin-induced Tim-3 expression in mice kidney tissues and proximal tubule-derived BUMPT cells in a time-dependent manner. Compared with wild-type mice, Tim-3 knockout mice have higher levels of serum creatinine and urea nitrogen, enhanced TUNEL staining signals, more severe 8-OHdG (8-hydroxy-2’ -deoxyguanosine) accumulation, and increased cleavage of caspase 3. The purified soluble Tim-3 (sTim-3) protein was used to intervene in cisplatin-stimulated BUMPT cells by competitively binding to the Tim-3 ligand. sTim-3 obviously increased the cisplatin-induced cell apoptosis. Under cisplatin treatment conditions, Tim-3 knockout or sTim-3 promoted the expression of TNF-α (tumor necrosis factor-alpha) and IL-1β (Interleukin-1 beta) and inhibited the expression of IL-10 (interleukin-10). NF-κB (nuclear factor kappa light chain enhancer of activated B cells) P65 inhibitor PDTC or TPCA1 lowed the increased levels of creatinine and BUN (blood urea nitrogen) in cisplatin-treated Tim-3 knockout mice serum and the increased cleavage of caspase 3 in sTim-3 and cisplatin-treated BUMPT cells. Moreover, sTim-3 enhanced mitochondrial oxidative stress in cisplatin-induced BUMPT cells, which can be mitigated by PDTC. These data indicate that Tim-3 may protect against renal injury by inhibiting NF-κB-mediated inflammation and oxidative stress.
Recent developments on BMPs and their antagonists in inflammatory bowel diseases
Authors: Xie Zhuo , Zhou Gaoshi , Zhang Mudan , Han Jing , Wang Ying , Li Xiaoling , Wu Qirui , Li Manying , Zhang Shenghong 
Published: July 2023

AbstractInflammatory bowel diseases (IBDs), including ulcerative colitis, and Crohn’s disease, are intestinal disorders characterized by chronic relapsing inflammation. A large proportion of patients with IBD will progress to develop colitis-associated colorectal cancer due to the chronic intestinal inflammation. Biologic agents that target tumour necrosis factor-α, integrin α4β7, and interleukin (IL)12/23p40 have been more successful than conventional therapies in treating IBD. However, drug intolerance and loss of response are serious drawbacks of current biologics, necessitating the development of novel drugs that target specific pathways in IBD pathogenesis. One promising group of candidate molecules are bone morphogenetic proteins (BMPs), members of the TGF-β family involved in regulating morphogenesis, homeostasis, stemness, and inflammatory responses in the gastrointestinal tract. Also worth examining are BMP antagonists, major regulators of these proteins. Evidence has shown that BMPs (especially BMP4/6/7) and BMP antagonists (especially Gremlin1 and follistatin-like protein 1) play essential roles in IBD pathogenesis. In this review, we provide an updated overview on the involvement of BMPs and BMP antagonists in IBD pathogenesis and in regulating the fate of intestinal stem cells. We also described the expression patterns of BMPs and BMP antagonists along the intestinal crypt-villus axis. Lastly, we synthesized available research on negative regulators of BMP signalling. This review summarizes recent developments on BMPs and BMP antagonists in IBD pathogenesis, which provides novel insights into future therapeutic strategies.
The role of CXCL family members in different diseases
Authors: Zhou Chenjia , Gao Ying , Ding Peilun , Wu Tao , Ji Guang 
Published: July 2023

AbstractChemokines are a large family mediating a lot of biological behaviors including chemotaxis, tumor growth, angiogenesis and so on. As one member of this family, CXC subfamily possesses the same ability. CXC chemokines can recruit and migrate different categories of immune cells, regulate tumor’s pathological behaviors like proliferation, invasion and metastasis, activate angiogenesis, etc. Due to these characteristics, CXCL subfamily is extensively and closely associated with tumors and inflammatory diseases. As studies are becoming more and more intensive, CXCLs’ concrete roles are better described, and CXCLs’ therapeutic applications including biomarkers and targets are also deeply explained. In this review, the role of CXCL family members in various diseases is summarized.
Nuclear transport maintenance of USP22-AR by Importin-7 promotes breast cancer progression
Authors: Cai Geng-Xi , Kong Wei-Yao , Liu Yuan , Zhong Shu-Yi , Liu Qing , Deng Yuan-Fei , Ye Guo-Lin 
Published: July 2023

AbstractThe translocation of biological macromolecules between cytoplasm and nucleus is of great significance to maintain various life processes in both normal and cancer cells. Disturbance of transport function likely leads to an unbalanced state between tumor suppressors and tumor-promoting factors. In this study, based on the unbiased analysis of protein expression differences with a mass spectrometer between human breast malignant tumors and benign hyperplastic tissues, we identified that Importin-7, a nuclear transport factor, is highly expressed in breast cancer (BC) and predicts poor outcomes. Further studies showed that Importin-7 promotes cell cycle progression and proliferation. Mechanistically, through co-immunoprecipitation, immunofluorescence, and nuclear–cytoplasmic protein separation experiments, we discovered that AR and USP22 can bind to Importin-7 as cargoes to promote BC progression. In addition, this study provides a rationale for a therapeutic strategy to restream the malignant progression of AR-positive BC by inhibiting the high expression state of Importin-7. Moreover, the knockdown of Importin-7 increased the responsiveness of BC cells to the AR signaling inhibitor, enzalutamide, suggesting that targeting Importin-7 may be a potential therapeutic strategy.
Rapid degeneration of iPSC-derived motor neurons lacking Gdap1 engages a mitochondrial-sustained innate immune response
Authors: León Marian , Prieto Javier , Molina-Navarro María Micaela , García-García Francisco , Barneo-Muñoz Manuela , Ponsoda Xavier , Sáez Rosana , Palau Francesc , Dopazo Joaquín , Izpisua Belmonte Juan Carlos , Torres Josema 
Published: July 2023

AbstractCharcot-Marie-Tooth disease is a chronic hereditary motor and sensory polyneuropathy targeting Schwann cells and/or motor neurons. Its multifactorial and polygenic origin portrays a complex clinical phenotype of the disease with a wide range of genetic inheritance patterns. The disease-associated gene GDAP1 encodes for a mitochondrial outer membrane protein. Mouse and insect models with mutations in Gdap1 have reproduced several traits of the human disease. However, the precise function in the cell types affected by the disease remains unknown. Here, we use induced-pluripotent stem cells derived from a Gdap1 knockout mouse model to better understand the molecular and cellular phenotypes of the disease caused by the loss-of-function of this gene. Gdap1-null motor neurons display a fragile cell phenotype prone to early degeneration showing (1) altered mitochondrial morphology, with an increase in the fragmentation of these organelles, (2) activation of autophagy and mitophagy, (3) abnormal metabolism, characterized by a downregulation of Hexokinase 2 and ATP5b proteins, (4) increased reactive oxygen species and elevated mitochondrial membrane potential, and (5) increased innate immune response and p38 MAP kinase activation. Our data reveals the existence of an underlying Redox-inflammatory axis fueled by altered mitochondrial metabolism in the absence of Gdap1. As this biochemical axis encompasses a wide variety of druggable targets, our results may have implications for developing therapies using combinatorial pharmacological approaches and improving therefore human welfare.
Directional induction of neural stem cells, a new therapy for neurodegenerative diseases and ischemic stroke
Authors: Nie Luwei , Yao Dabao , Chen Shiling , Wang Jingyi , Pan Chao , Wu Dongcheng , Liu Na , Tang Zhouping 
Published: July 2023

AbstractDue to the limited capacity of the adult mammalian brain to self-repair and regenerate, neurological diseases, especially neurodegenerative disorders and stroke, characterized by irreversible cellular damage are often considered as refractory diseases. Neural stem cells (NSCs) play a unique role in the treatment of neurological diseases for their abilities to self-renew and form different neural lineage cells, such as neurons and glial cells. With the increasing understanding of neurodevelopment and advances in stem cell technology, NSCs can be obtained from different sources and directed to differentiate into a specific neural lineage cell phenotype purposefully, making it possible to replace specific cells lost in some neurological diseases, which provides new approaches to treat neurodegenerative diseases as well as stroke. In this review, we outline the advances in generating several neuronal lineage subtypes from different sources of NSCs. We further summarize the therapeutic effects and possible therapeutic mechanisms of these fated specific NSCs in neurological disease models, with special emphasis on Parkinson’s disease and ischemic stroke. Finally, from the perspective of clinical translation, we compare the strengths and weaknesses of different sources of NSCs and different methods of directed differentiation, and propose future research directions for directed differentiation of NSCs in regenerative medicine.
Hyperbolic polaritonic crystals with configurable low-symmetry Bloch modes
Authors: Lv Jiangtao , Wu Yingjie , Liu Jingying , Gong Youning , Si Guangyuan , Hu Guangwei , Zhang Qing , Zhang Yupeng , Tang Jian-Xin , Fuhrer Michael S. , Chen Hongsheng , Maier Stefan A. , Qiu Cheng-Wei , Ou Qingdong 
Published: July 2023

AbstractPhotonic crystals (PhCs) are a kind of artificial structures that can mold the flow of light at will. Polaritonic crystals (PoCs) made from polaritonic media offer a promising route to controlling nano-light at the subwavelength scale. Conventional bulk PhCs and recent van der Waals PoCs mainly show highly symmetric excitation of Bloch modes that closely rely on lattice orders. Here, we experimentally demonstrate a type of hyperbolic PoCs with configurable and low-symmetry deep-subwavelength Bloch modes that are robust against lattice rearrangement in certain directions. This is achieved by periodically perforating a natural crystal α-MoO3 that hosts in-plane hyperbolic phonon polaritons. The mode excitation and symmetry are controlled by the momentum matching between reciprocal lattice vectors and hyperbolic dispersions. We show that the Bloch modes and Bragg resonances of hyperbolic PoCs can be tuned through lattice scales and orientations while exhibiting robust properties immune to lattice rearrangement in the hyperbolic forbidden directions. Our findings provide insights into the physics of hyperbolic PoCs and expand the categories of PhCs, with potential applications in waveguiding, energy transfer, biosensing and quantum nano-optics.
SUMOylation of Rho-associated protein kinase 2 induces goblet cell metaplasia in allergic airways
Authors: Tan Dan , Lu Meiping , Cai Yuqing , Qi Weibo , Wu Fugen , Bao Hangyang , Qv Meiyu , He Qiangqiang , Xu Yana , Wang Xiangzhi , Shen Tingyu , Luo Jiahao , He Yangxun , Wu Junsong , Tang Lanfang , Barkat Muhammad Qasim , Xu Chengyun , Wu Ximei 
Published: July 2023

AbstractAllergic asthma is characterized by goblet cell metaplasia and subsequent mucus hypersecretion that contribute to the morbidity and mortality of this disease. Here, we explore the potential role and underlying mechanism of protein SUMOylation-mediated goblet cell metaplasia. The components of SUMOylaion machinery are specifically expressed in healthy human bronchial epithelia and robustly upregulated in bronchial epithelia of patients or mouse models with allergic asthma. Intratracheal suppression of SUMOylation by 2-D08 robustly attenuates not only allergen-induced airway inflammation, goblet cell metaplasia, and hyperreactivity, but IL-13-induced goblet cell metaplasia. Phosphoproteomics and biochemical analyses reveal SUMOylation on K1007 activates ROCK2, a master regulator of goblet cell metaplasia, by facilitating its binding to and activation by RhoA, and an E3 ligase PIAS1 is responsible for SUMOylation on K1007. As a result, knockdown of PIAS1 in bronchial epithelia inactivates ROCK2 to attenuate IL-13-induced goblet cell metaplasia, and bronchial epithelial knock-in of ROCK2(K1007R) consistently inactivates ROCK2 to alleviate not only allergen-induced airway inflammation, goblet cell metaplasia, and hyperreactivity, but IL-13-induced goblet cell metaplasia. Together, SUMOylation-mediated ROCK2 activation is an integral component of Rho/ROCK signaling in regulating the pathological conditions of asthma and thus SUMOylation is an additional target for the therapeutic intervention of this disease.
Lean-water hydrogel electrolyte for zinc ion batteries
Authors: Wang Yanbo , Li Qing , Hong Hu , Yang Shuo , Zhang Rong , Wang Xiaoqi , Jin Xu , Xiong Bo , Bai Shengchi , Zhi Chunyi 
Published: July 2023

AbstractSolid polymer electrolytes (SPEs) and hydrogel electrolytes were developed as electrolytes for zinc ion batteries (ZIBs). Hydrogels can retain water molecules and provide high ionic conductivities; however, they contain many free water molecules, inevitably causing side reactions on the zinc anode. SPEs can enhance the stability of anodes, but they typically possess low ionic conductivities and result in high impedance. Here, we develop a lean water hydrogel electrolyte, aiming to balance ion transfer, anode stability, electrochemical stability window and resistance. This hydrogel is equipped with a molecular lubrication mechanism to ensure fast ion transportation. Additionally, this design leads to a widened electrochemical stability window and highly reversible zinc plating/ stripping. The full cell shows excellent cycling stability and capacity retentions at high and low current rates, respectively. Moreover, superior adhesion ability can be achieved, meeting the needs of flexible devices.
Swift and extensive Omicron outbreak in China after sudden exit from ‘zero-COVID’ policy
Authors: Goldberg Emma E. , Lin Qianying , Romero-Severson Ethan O. , Ke Ruian 
Published: July 2023

AbstractIn late 2022, China transitioned from a strict ‘zero-COVID’ policy to rapidly abandoning nearly all interventions and data reporting. This raised great concern about the presumably-rapid but unreported spread of the SARS-CoV-2 Omicron variant in a very large population of very low pre-existing immunity. By modeling a combination of case count and survey data, we show that Omicron spread extremely rapidly, at a rate of 0.42/day (95% credibility interval: [0.35, 0.51]/day), translating to an epidemic doubling time of 1.6 days ([1.6, 2.0] days) after the full exit from zero-COVID on Dec. 7, 2022. Consequently, we estimate that the vast majority of the population (97% [95%, 99%], sensitivity analysis lower limit of 90%) was infected during December, with the nation-wide epidemic peaking on Dec. 23. Overall, our results highlight the extremely high transmissibility of the variant and the importance of proper design of intervention exit strategies to avoid large infection waves.
Architecture of a complete Bce-type antimicrobial peptide resistance module
Authors: George Natasha L. , Orlando Benjamin J. 
Published: July 2023

AbstractGram-positive bacteria synthesize and secrete antimicrobial peptides that target the essential process of peptidoglycan synthesis. These antimicrobial peptides not only regulate the dynamics of microbial communities but are also of clinical importance as exemplified by peptides such as bacitracin, vancomycin, and daptomycin. Many gram-positive species have evolved specialized antimicrobial peptide sensing and resistance machinery known as Bce modules. These modules are membrane protein complexes formed by an unusual Bce-type ABC transporter interacting with a two-component system sensor histidine kinase. In this work, we provide the first structural insight into how the membrane protein components of these modules assemble into a functional complex. A cryo-EM structure of an entire Bce module revealed an unexpected mechanism of complex assembly, and extensive structural flexibility in the sensor histidine kinase. Structures of the complex in the presence of a non-hydrolysable ATP analog reveal how nucleotide binding primes the complex for subsequent activation. Accompanying biochemical data demonstrate how the individual membrane protein components of the complex exert functional control over one another to create a tightly regulated enzymatic system.
GNSS land subsidence observations along the northern coastline of Java, Indonesia
Authors: Susilo Susilo , Salman Rino , Hermawan Wawan , Widyaningrum Risna , Wibowo Sidik Tri , Lumban-Gaol Yustisi Ardhitasari , Meilano Irwan , Yun Sang-Ho 
Published: July 2023

AbstractLand subsidence in cities along the northern coastline of Java has been at a worrying level. Monitoring efforts using geodetic data reveal that Jakarta, Pekalongan, Semarang, and Demak subside at least ~9x faster than the present-day rate of global sea level rise, which affects the cities’ future urban viability. In this study, we publish a time series of the precise 3D displacements observed by twenty continuous Global Navigation Satellite System (GNSS) stations between 2010 and 2021. These are the first open-to-the-public and rigorously processed GNSS datasets that are useful for accurately quantifying land subsidence in the densely populated sinking cities in Java. The data also provides a way to tie other geodetic observations, such as Interferometric Synthetic Aperture Radar (InSAR), to a global reference frame in an attempt to build worldwide observations of coastal land subsidence.
Comparative effectiveness of Cangrelor in patients with acute coronary syndrome undergoing percutaneous coronary intervention: an observational investigation from the M.O.Ca. registry
Authors: Pepe Martino , Carulli Eugenio , Larosa Claudio , Napoli Gianluigi , Nestola Palma Luisa , Carella Maria Cristina , Giordano Salvatore , Tritto Rocco , Bartolomucci Francesco , Cirillo Plinio , Zoccai Giuseppe Biondi , Giordano Arturo , Ciccone Marco Matteo 
Published: July 2023

AbstractCangrelor, the first intravenous P2Y12 inhibitor (P2Y12-I), has been approved on the basis of three large RCTs from the CHAMPION program which nevertheless have been criticized for the low bleeding risk of the enrolled patients, the large quote of chronic coronary syndromes, and the use of Clopidogrel as control arm even in the setting of acute coronary syndromes (ACS). We sought to investigate, in the setting of ACS, the comparative performance of Cangrelor in terms of in-hospital ischemic and haemorrhagic outcomes compared with the current gold-standard of oral P2Y12-I. The study retrospectively enrolled 686 consecutive patients admitted to the Divisions of Cardiology of Policlinico of Bari and L. Bonomo Hospital of Andria for ACS and treated with percutaneous coronary intervention. The study population was divided according to the P2Y12-I treatment strategy in two groups: patients given an oral P2Y12-I and patients receiving Cangrelor in the cath lab followed by an oral P2Y12-I. Clinical endpoints included death, ischemic and bleeding events occurring during hospital stay. Cangrelor treated patients presented higher clinical risk profile at presentation and faced higher death rate. However, after PS matching, in-hospital mortality resulted comparable between the groups and Cangrelor use was associated with reduced in-hospital definite stent thrombosis (p = 0.03). Data from our real-world registry highlight that, in the setting of ACS, Cangrelor is prevalently used in patients with very challenging clinical presentations. The adjusted analysis provides for the first time promising data on stent thrombosis reduction associated with Cangrelor use.
Spouse’s coping strategies mediate the relationship between women’s coping strategies and their psychological health among infertile couples
Authors: Reisi Marzie , Kazemi Ashraf , Abedi Mohammad Reza , Nazarian Naser 
Published: July 2023

AbstractSocial problems and suffering from the treatment process for infertile couples, especially for women, require the couples to cope with them to balance the infertility crisis. According to the close interactions of the couples with each other, the objective of the present study was to explore a theoretical framework for the relationships between women’s coping strategies, spouses’ coping strategies, and women’s psychological health in infertile couples who were candidates for assisted reproductive technology (ART). This cross-sectional study was carried out on 212 couples undergoing ART. The couples’ coping strategies were evaluated using a validated self-report questionnaire. The women’s psychological health was assessed using a 21-item stress, anxiety, and depression scale (DASS-21). Statistical analysis was performed using the plug-in application PROCESS macro for SPSS. The direct effect of the women’s self-blame and self-focused rumination strategies (p < .0001), and the indirect effect of the women’s self-blame on stress and depression by mediating spouses’ self-blame and self-focused rumination strategies, was significant. The indirect effect of the women’s self-focused rumination on the anxiety and depression levels by mediating spouses’ self-blame strategy was significant. The women’s self-blame and self-focused rumination strategies had a negative effect on the women’s psychological health who were undergoing ART. This negative effect was mediated by the spouse’s coping strategies.