bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stabilization of TGF‐β Receptor 1 by a Receptor‐Associated Adaptor Dictates Feedback Activation of the TGF‐β Signaling Pathway to Maintain Liver Cancer Stemness and Drug Resistance
Authors: Liu Kewei , Tian Fanxuan , Chen Xu , Liu Biyin , Tian Shuoran , Hou Yongying , Wang Lei , Han Mengyi , Peng Shiying , Tan Yuting , Pan Yuwei , Chu Zhaole , Li Jinyang , Che Linrong , Chen Dongfeng , Wen Liangzhi , Qin Zhongyi , Li Xianfeng , Xiang Junyu , Bian Xiu‐wu , Liu Qin , Ye Xiaoli , Wang Tao , Wang Bin 
Published: July 2024

AbstractDysregulation of the transforming growth factor‐β (TGF‐β) signaling pathway regulates cancer stem cells (CSCs) and drug sensitivity, whereas it remains largely unknown how feedback regulatory mechanisms are hijacked to fuel drug‐resistant CSCs. Through a genome‐wide CRISPR activation screen utilizing stem‐like drug‐resistant properties as a readout, the TGF‐β receptor‐associated binding protein 1 (TGFBRAP1) is identified as a TGF‐β‐inducible positive feedback regulator that governs sensitivity to tyrosine kinase inhibitors (TKIs) and promotes liver cancer stemness. By interacting with and stabilizing the TGF‐β receptor type 1 (TGFBR1), TGFBRAP1 plays an important role in potentiating TGF‐β signaling. Mechanistically, TGFBRAP1 competes with E3 ubiquitin ligases Smurf1/2 for binding to TGFΒR1, leading to impaired receptor poly‐ubiquitination and proteasomal degradation. Moreover, hyperactive TGF‐β signaling in turn up‐regulates TGFBRAP1 expression in drug‐resistant CSC‐like cells, thereby constituting a previously uncharacterized feedback mechanism to amplify TGF‐β signaling. As such, TGFBRAP1 expression is correlated with TGFΒR1 levels and TGF‐β signaling activity in hepatocellular carcinoma (HCC) tissues, as well as overall survival and disease recurrence in multiple HCC cohorts. Therapeutically, blocking TGFBRAP1‐mediated stabilization of TGFBR1 by selective inhibitors alleviates Regorafenib resistance via reducing CSCs. Collectively, targeting feedback machinery of TGF‐β signaling pathway may be an actionable approach to mitigate drug resistance and liver cancer stemness.
A Microenvironment‐Responsive, Controlled Release Hydrogel Delivering Embelin to Promote Bone Repair of Periodontitis via Anti‐Infection and Osteo‐Immune Modulation
Authors: Cai Guanming , Ren Lin , Yu Jiali , Jiang Siqi , Liu Gen , Wu Shujie , Cheng Bin , Li Weichang , Xia Juan 
Published: July 2024

AbstractPeriodontitis, a prevalent chronic inflammatory disease, poses significant challenges for effective treatment due to its complex etiology involving specific bacteria and the inflammatory immune microenvironment. Here, this study presents a novel approach for the targeted treatment of periodontitis utilizing the immunomodulatory and antibacterial properties of Embelin, a plant‐derived compound, within an injectable hydrogel system. The developed Carboxymethyl Chitosan‐Oxidized Dextran (CMCS‐OD) hydrogel formed via dynamic chemical bonds exhibited self‐healing capabilities and pH‐responsive behavior, thereby facilitating the controlled release of Embelin and enhancing its efficacy in a dynamic oral periodontitis microenvironment. This study demonstrates that this hydrogel system effectively prevents bacterial invasion and mitigates excessive immune response activation. Moreover, it precisely modulates macrophage M1/M2 phenotypes and suppresses inflammatory cytokine expression, thereby fostering a conducive environment for bone regeneration and addressing periodontitis‐induced bone loss. These findings highlight the potential of the approach as a promising strategy for the clinical management of periodontitis‐induced bone destruction.
Stretching, Tapping, or Compressing–What Role Does Triboelectricity Play in the Signal Output from Piezoelectric Nanogenerators?
Authors: Akbarinejad Alireza , Fiedler Holger , Nguyen Jade , Li Zifan , Gito Donn Adam , Sherrell Peter C. , Ellis Amanda V. , Aw Kean , Malmstrom Jenny 
Published: July 2024

AbstractPiezoelectric energy generation is relevant for developing advanced electronics. However, the poor understanding of the influence of triboelectricity as an alternate charge generation mechanism has, in many cases, resulted in the reporting of exaggerated piezoelectric outputs. Herein, the signal output is systematically investigated from a range of organic piezoelectric materials (poled polyvinylidene fluoride (PVDF)), moderately piezoelectric (heat‐treated PVDF), and non‐piezoelectric (non‐poled PVDF), polytetrafluoroelthylene (Teflon) and nylon) under tapping and compression (33 direction) and stretching (31 direction) in both encapsulated and non‐encapsulated forms. This findings reveal that regardless of their piezoelectric properties, all tested materials exhibit substantial voltage outputs (4.2–4.6 V) during tapping, primarily attributed to the triboelectric effect at the contact interface. The triboelectric contribution to the signal is reduced by 99% in compression mode for non‐piezoelectric materials and the piezoelectric signal is the primary contributor in the stretching mode with a high signal output of 7.71 V N−1 for poled PVDF and a negligible signal (0.01–0.12 V N−1) for non‐piezoelectric materials. Moreover, elastomeric encapsulation is demonstrated to markedly increase triboelectric signals in tapping mode. These results have important implications for the future design of piezoelectric‐triboelectric devices and the accurate interpretation of the data obtained from such devices.
Silicon‐Inspired Analysis of Interfacial Recombination in Perovskite Photovoltaics
Authors: Gillespie Sarah C. , Gautier Jérôme , van der Burgt Julia S. , Anker John , Geerligs Bart L.J. , Coletti Gianluca , Garnett Erik C. 
Published: July 2024

AbstractPerovskite solar cells have reached an impressive certified efficiency of 26.1%, with a considerable fraction of the remaining losses attributed to carrier recombination at perovskite interfaces. This work demonstrates how time‐resolved photoluminescence spectroscopy (TRPL) can be utilized to locate and quantify remaining recombination losses in perovskite solar cells, analogous to methods established to improve silicon solar cell passivation and contact layers. It is shown how TRPL analysis can be extended to determine the bulk and surface lifetimes, surface recombination velocity, the recombination parameter, J0, and the implied open‐circuit voltage (iVoc) of any perovskite device configuration. This framework is used to compare 18 carrier‐selective and passivating contacts commonly used or emerging for perovskite photovoltaics. Furthermore, the iVoc values calculated from the TRPL‐based framework are directly compared to those calculated from photoluminescence quantum yields and the measured solar cell Voc. This simple technique serves as a practical guide for screening and selecting multifunctional, passivating perovskite contact layers. As with silicon solar cells, most of the material and interface analysis can be done without fabricating full devices or measuring efficiency. These purely optical measurements are even preferable when studying bulk and interfacial passivation approaches, since they remove complicating effects from poor carrier extraction.
DNA nanomachine‐driven chemodynamic therapy against glioblastoma
Authors: Li Xiaodie , Lan Yufei , Fu Xin , Luo Xin , Chen Jie , Zhang Wenxin , Zuo Boming , Yang Tao , Liu Boyang , Zhang Chao , Guo Hongbo 
Published: July 2024

AbstractChemodynamic therapy (CDT) has shown promising antitumor effects in various malignant tumors. However, its application for glioblastoma (GBM) is significantly hindered by the challenge of delivering CDT agents across the blood‐brain barrier (BBB) and achieving efficient tumor targeting. To overcome these obstacles, this study presents a novel DNA nanomachine (Cu@tFNAs‐G‐A NM) by loading copper ions (Cu2+) onto tetrahedral framework nucleic acids (tFNAs) functionalized with dual DNA aptamers. The dual DNA aptamers (GS24 for BBB penetration and AS1411 for tumor targeting) empowered Cu@tFNAs‐G‐A NM with the ability to effectively penetrate the BBB and selectively accumulate in tumor cells. Upon internalization, the loaded Cu2+ reacted with tumor‐overexpressed reductive glutathione (GSH) and hydrogen peroxide (H2O2), generating hydroxyl radicals (·OH) and inducing tumor cell death. Additionally, Cu@tFNAs‐G‐A NM was found to be rapidly cleared from the brain and normal tissues within 24 h, minimizing potential systemic toxic side effects. These findings demonstrate the promising potential of Cu@tFNAs‐G‐A NM for effective CDT against GBM and open up new avenues for the development of targeted therapies for GBM.
Safety and efficacy of baricitinib in steroid‐resistant or relapsed immune thrombocytopenia: An open‐label pilot study
Authors: Zhao Peng , An Zhuo‐Yu , Fu Hai‐Xia , Liu Hui‐Xin , Feng Cheng‐Jie , Huang Qiu‐Sha , Wu Jin , Wu Ye‐Jun , Yang Li‐Ping , Qu Qing‐Yuan , Chen Yu‐Xiu , Li Meng‐Lin , Wang Chen‐Cong , Chen Qi , Zhu Xiao‐Lu , He Yun , Zhang Yuan‐Yuan , Jiang Qian , Jiang Hao , Lu Jin , Chang Ying‐Jun , Zhao Xiao‐Su , Zhao Xiang‐Yu , Huang Xiao‐Jun , Zhang Xiao‐Hui 
Published: July 2024

AbstractPatients with steroid‐resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus‐associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open‐label, single‐arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6‐month follow‐up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6–20) days, and the median peak platelet count was 94 (IQR 72–128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP‐modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.
Population expansion, larger, and more homogeneous native American ancestry among Mexican mestizo populations based on 10 X‐chromosome STR loci (X‐STR decaplex system)
Authors: Mariscal‐Ramos Christian , Cortes‐Trujllo Irán , Martínez‐Cortés Gabriela , Arana Ismael Nuño , Rangel‐Villalobos Héctor 
Published: July 2024

AbstractObjectiveTo evaluate the genetic diversity, admixture, genetic relationships, and sex‐biased demographic processes in Mexican Mestizo (admixed) populations based on 10 X‐chromosome STRs (X‐STRs).MethodsWe analyzed the X‐STRs Decaplex system in 104 Mexican Native Americans to obtain the ancestral reference needed to complete the demographic analyses above mentioned. We included reported Iberian and Latin American (admixed) populations from Central and South America, as well as datasets from Mexican Mestizos based on Y‐linked STRs (Y‐STRs), autosomal STRs (A‐STRs), and mtDNA.ResultsHigher X‐linked Native American ancestry was observed among Latin American populations regarding that reported from A‐STRs and Y‐STRs. The interpopulation differentiation based on ancestry among Mexican Mestizos diminished according to the inheritance pattern: Y‐STRs (highest), A‐STRs, X‐STRs, and mtDNA (lowest). This finding is related to the peculiar admixture process that occurred during and after the Spanish Conquest of Mexico (and most of Latin America), involving a large number of Spanish men (Y‐chromosomes) with a lesser proportion of X‐chromosomes than autosomes; besides to the limited number of Spanish women (XX) arrived in the Americas in subsequent and shorter periods. Population expansion was detected in Mexican Mestizos from all the country, except those from the southeast region characterized by elevated indigenous ancestry, marginalization, and poorness.ConclusionsPopulation growth was detected in most Mexican Mestizos, besides more homogeneous and larger Native American ancestry based on X‐linked inheritance than that based on autosomal STRs and Y‐STRs.
Bone density in postmenopausal women with scoliosis is associated with markers of degenerative joint disease
Authors: Ganji Elahe , Burshell Alan , Khicha Amisha , Lee Katharine M. N. 
Published: July 2024

AbstractPurposeBone mineral density (BMD) measured with dual x‐ray absorptiometry (DXA) is the clinical standard for the diagnosis of osteoporosis and prediction of bone fracture risk. In the aging skeleton, osteoporosis is often concomitantly present with degenerative joint disease (DJD).MethodsIn this study, we evaluated tissue‐level changes in the differentially loaded concave (CC) and convex (CV) sides of the lumbar spine in a sample of postmenopausal women with scoliosis. We used a cumulative degeneration score to assess osteophyte formation, the severity of sclerotic morphology, and marrow changes as markers of DJD in the lumbar spine and examined the correlation between markers of DJD and BMD.ResultsMore severe osteophyte growth and sclerosis were present on the CC side of the spine. The degenerative score (DS) was higher on the CC side of the lumbar spine compared with the CV side. While CC BMD was positively correlated with CC DS and marrow, CV DS was not correlated with CV BMD. Marrow changes were correlated with DS on the CC lumbar spine.ConclusionThese results highlight the importance of mechanoadaptive as well as broader inflammatory processes in the manifestation of degenerative changes and local mineral deposition at the lumbar spine. DXA‐based BMD measurement of osteoporosis need to be contextualized within the biomechanical and degenerative conditions of a joint rather than using a strict threshold cutoff.
Comparison of internal and external reference populations for occupational cancer surveillance in a cohort drawn from a diverse workforce
Authors: Everest Louis , Tan Shirui , Navaneelan Tanya , Demers Paul A. , DeBono Nathan , Berriault Colin , Sritharan Jeavana 
Published: July 2024

AbstractObjectivesPrior analyses of the Occupational Disease Surveillance System (ODSS) have compared cancer rates using internal referent groups. As an exploratory analysis, we sought to estimate cancer risk using general population reference rates to evaluate the impact that the comparison population has on findings from our surveillance program.MethodsA cohort of approximately 2.3 million workers in Ontario, Canada with an accepted lost‐time workers' compensation claim were followed for all cancer diagnoses between 1983 and 2018. Standardized incidence ratios (SIRs) and 95% confidence intervals were calculated for workers in specific occupational groups using (1) all other workers in the ODSS cohort, and (2) the general population of Ontario.ResultsSIRs using the general population reference group were generally equal to or modestly lower compared to SIRs using the internal reference group. Within occupation groups, SIRs had a discordant direction of association (increased rate in the internal comparison and decreased in the external comparison) for some cancer sites including urinary, prostate, and colorectal.ConclusionsFindings emphasize the importance of the choice of reference group when evaluating cancer risks in large occupational surveillance cohorts. Importantly, the magnitude of confounding and the healthy worker hire bias may depend on the occupation group and cancer site of interest.
Ultra‐high‐performance liquid chromatography‐quadrupole time‐of‐flight‐mass spectrometry‐characterized extract of Aerides odorata Lour alleviates paracetamol‐induced hepatotoxicity in animal model evidenced by biochemical, molecular, and computational studies
Authors: Ahmed A. M. Abu , Rahman Md. Atiar , Sharmen Farjana , Reza A. S. M. Ali , Islam Md. Shahidul , Rashid Md. Mamunur , Rafi Md. Khalid Juhani , Siddiqui Tanvir Ahmed , Ezaj Md. Muzahid Ahmed , Saha Srabonti , Uddin Md. Nazim , Alelwani Walla 
Published: July 2024

AbstractBackgroundMany kinds of orchids have significant health benefits although adequate research on their biological functions is yet to be carried out. This study investigated the paracetamol‐induced liver damage–protecting effect of epiphytic Aerides odorata methanol extract (AODE).MethodsThe protective effects of AODE were studied by analyzing its effect on liver function parameters, messenger RNA (mRNA) expression, and tissue histopathological architecture. The results were confirmed by ligand–receptor interaction of molecular docking and multitarget interaction of network pharmacological analyses.ResultsAODE significantly (p < 0.05) minimized the dose‐dependent increase in acid phosphatase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, γ‐glutamyl transferase, lactate dehydrogenase, and total bilirubin compared to the reference drug silymarin. Malondialdehyde level decreased, and the antioxidant genes catalase (CAT), superoxide dismutase (SOD), β‐actin, paraoxonase‐1 (PON1), and phosphofructokinase‐1 (PFK‐1) were upregulated in AODE‐treated paracetamol‐intoxicated rats. A total of 376 compounds comprising phenols and flavonoids were identified using ultra‐high‐performance liquid chromatography‐quadrupole time‐of‐flight‐mass spectrometry (UPLC‐qTOF‐MS). The online toxicity assessment using SwissADME and admetSAR exhibited drug‐like, nontoxic, and potential pharmacological properties. Additionally, in silico analysis showed that isoacteoside, one of the identified compounds, exhibited the best docking score (−11.42) with the liver protein human pituitary adenylate cyclase‐1 (Protein Data Bank ID: 3N94). Furthermore, network pharmacology analysis identified the top 10 hub genes, namely AKT1 (protein kinase B), CTNNB1 (catenin beta‐1), SRC (proto‐oncogene c‐Src), TNF (tumor necrosis factor), EGFR (epidermal growth factor receptor), HSP90AA1 (heat shock protein 90α), MAPK3 (mitogen‐activated protein kinase 3), STAT3 (signal transducer and activator of transcription 3), CASP3 (caspase protein), and ESR1 (estrogen receptor 1), which are responsible for hepatoprotective activity.ConclusionThe findings demonstrate that AODE could be a novel hepatoprotective target in drug‐induced liver damage with a further single compound–based animal study.
Effect of macrophage‐to‐myofibroblast transition on silicosis
Authors: Geng Fei , Xu Jingrou , Ren Xichen , Zhao Ying , Cai Yuhao , Li Yaqian , Jin Fuyu , Li Tian , Gao Xuemin , Cai Wenchen , Xu Hong , Wei Zhongqiu , Mao Na , Sun Ying , Yang Fang 
Published: July 2024

AbstractBackgroundThe aim was to explore the effect of macrophage polarization and macrophage‐to‐myofibroblast transition (MMT) in silicosis.MethodsMale Wistar rats were divided into a control group and a silicosis group developed using a HOPE MED 8050 dynamic automatic dusting system. Murine macrophage MH‐S cells were randomly divided into a control group and an SiO2 group. The pathological changes in lung tissue were observed using hematoxylin and eosin (HE) and Van Gieson (VG) staining. The distribution and location of macrophage marker (F4/80), M1 macrophage marker (iNOS), M2 macrophage marker (CD206), and myofibroblast marker (α‐smooth muscle actin [α‐SMA]) were detected using immunohistochemical and immunofluorescent staining. The expression changes in iNOS, Arg, α‐SMA, vimentin, and type I collagen (Col I) were measured using Western blot.ResultsThe results of HE and VG staining showed obvious silicon nodule formation and the distribution of thick collagen fibers in the lung tissue of the silicosis group. Macrophage marker F4/80 increased gradually from 8 to 32 weeks after exposure to silica. Immunohistochemical and immunofluorescent staining results revealed that there were more iNOS‐positive cells and some CD206‐positive cells in the lung tissue of the silicosis group at 8 weeks. More CD206‐positive cells were found in the silicon nodules of the lung tissues in the silicosis group at 32 weeks. Western blot analysis showed that the expressions of Inducible nitric oxide synthase and Arg protein in the lung tissues of the silicosis group were upregulated compared with those of the control group. The results of immunofluorescence staining showed the co‐expression of F4/80, α‐SMA, and Col I, and CD206 and α‐SMA were co‐expressed in the lung tissue of the silicosis group. The extracted rat alveolar lavage fluid revealed F4/80+α‐SMA+, CD206+α‐SMA+, and F4/80+α‐SMA+Col I+ cells using immunofluorescence staining. Similar results were also found in MH‐S cells induced by SiO2.ConclusionsThe development of silicosis is accompanied by macrophage polarization and MMT.
Engineered Cellular Vesicles Displaying Glycosylated Nanobodies for Cancer Immunotherapy
Authors: Wu Jicheng , Lu Hailin , Xu Ximing , Rao Lang , Ge Yun 
Published: July 2024

AbstractImmune checkpoint blockade targeting the CD47/SIRPα axis represents an alluring avenue for cancer immunotherapy. However, the compromised efficacy and safety concerns in vivo of conventional anti‐CD47 antibodies impede their wide clinical applications. Here we introduced a single type of high‐mannose glycans into the nanobody against CD47 (HM‐nCD47) and subsequently displayed HM‐nCD47 on cellular vesicles (CVs) for enhanced cancer immunotherapy. In this platform, the CVs significantly improved the circulation time of HM‐nCD47‐CVs, the nCD47 enabled the blockade of the CD47/SIRPα axis, and the HM enhanced recognition of mannose‐binding lectin, all synergistically activating the macrophage‐mediated antitumor immunity. In both subcutaneous and metastatic murine tumor models, the HM‐nCD47‐CVs possessed significantly extended half‐lives and increased accumulation at the tumor site, resulting in a remarkable macrophage‐dependent inhibition of tumor growth, a transcriptomic remodeling of the immune response, and an increase in survival time. By integrating the chemical biology toolbox with cell membrane nanotechnology, the HM‐nCD47‐CVs represent a new immunotherapeutic platform for cancer and other diseases.
Divergent Synthesis of 17‐nor‐Cephalotane Diterpenoids through Developed Ynol‐diene Cyclization
Authors: Sun Zezhong , Shu Xin , Ma Fuli , Li Ao , Li Yali , Jin Shuang , Wang Yunxia , Hu Xiangdong 
Published: July 2024

AbstractOn the basis of a novel ynol‐diene cyclization developed as a rapid access to tropone unit, the first divergent strategy to 17‐nor‐cephalotane diterpenoids has been successfully established. Combining with a bioinspired stereoselective dual hydrogenation, the divergent total synthesis of (+)‐3‐deoxyfortalpinoid F, (+)‐harringtonolide, (−)‐fortalpinoids M/N/P, and analog (−)‐20‐deoxocephinoid P have been achieved in 14–17 linear longest steps starting from commercially available materials.