bluuebunny/crossref_metadata_2025_split huggingface dataset:
A biomimetic nanoplatform for customized photothermal therapy of HNSCC evaluated on patient-derived xenograft models
Authors: Wu Qi , Chen Lan , Huang Xiaojuan , Lin Jiayi , Gao Jiamin , Yang Guizhu , Wu Yaping , Wang Chong , Kang Xindan , Yao Yanli , Wang Yujue , Xue Mengzhu , Luan Xin , Chen Xin , Zhang Zhiyuan , Sun Shuyang 
Published: February 2023

AbstractCancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.
Salinity determines performance, functional populations, and microbial ecology in consortia attenuating organohalide pollutants
Authors: Xu Guofang , Zhao Xuejie , Zhao Siyan , Rogers Matthew J , He Jianzhong 
Published: February 2023

Abstract
Organohalide pollutants are prevalent in coastal regions due to extensive intervention by anthropogenic activities, threatening public health and ecosystems. Gradients in salinity are a natural feature of coasts, but their impacts on the environmental fate of organohalides and the underlying microbial communities remain poorly understood. Here we report the effects of salinity on microbial reductive dechlorination of tetrachloroethene (PCE) and polychlorinated biphenyls (PCBs) in consortia derived from distinct environments (freshwater and marine sediments). Marine-derived microcosms exhibited higher halotolerance during PCE and PCB dechlorination, and a halotolerant dechlorinating culture was enriched from these microcosms. The organohalide-respiring bacteria (OHRB) responsible for PCE and PCB dechlorination in marine microcosms shifted from Dehalococcoides to Dehalobium when salinity increased. Broadly, lower microbial diversity, simpler co-occurrence networks, and more deterministic microbial community assemblages were observed under higher salinity. Separately, we observed that inhibition of dechlorination by high salinity could be attributed to suppressed viability of Dehalococcoides rather than reduced provision of substrates by syntrophic microorganisms. Additionally, the high activity of PCE dechlorinating reductive dehalogenases (RDases) in in vitro tests under high salinity suggests that high salinity likely disrupted cellular components other than RDases in Dehalococcoides. Genomic analyses indicated that the capability of Dehalobium to perform dehalogenation under high salinity was likely owing to the presence of genes associated with halotolerance in its genomes. Collectively, these mechanistic and ecological insights contribute to understanding the fate and bioremediation of organohalide pollutants in environments with changing salinity.
Identification of a virulent phage infecting species of Nitrosomonas
Authors: Quirós Pablo , Sala-Comorera Laura , Gómez-Gómez Clara , Ramos-Barbero María Dolores , Rodríguez-Rubio Lorena , Vique Gloria , Yance-Chávez Tula , Atarés Sergio , García-Gutierrez Sandra , García-Marco Sonia , Vallejo Antonio , Salaet Ignasi , Muniesa Maite 
Published: February 2023

Abstract
In the first and limiting step of nitrification, ammonia (NH3) is oxidised to nitrite (NO2−) by the action of some prokaryotes, including bacteria of the Nitrosomonas genus. A potential approach to nitrification inhibition would be through the application of phages, but until now this method has been unexplored and no virulent phages that infect nitrifying bacteria have been described. In this study, we report the isolation of the first phage infecting some Nitrosomonas species. This polyvalent virulent phage (named ΦNF-1) infected Nitrosomonas europaea, Nitrosomonas communis, and Nitrosomonas nitrosa. Phage ΦNF-1 has the morphology of the Podoviridae family, a dsDNA genome of 41,596 bp and a 45.1 % GC content, with 50 predicted open reading frames. Phage ΦNF-1 was found to inhibit bacterial growth and reduce NH4+ consumption in the phage-treated cultures. The application of phages as biocontrol agents could be a useful strategy for nitrification inhibition without the restrictions associated with chemical inhibitors.
Economic burden of becoming a dentist in Thailand
Authors: Tussanapirom Teerawat , Siribal Prachya , Trirattanaphinthusorn Phiranat , Kengtong Witchapat , Gaewkhiew Piyada 
Published: February 2023

AbstractObjectivesTo determine the overall estimated financial impact and related expenses incurred over the duration of the undergraduate Dental Degree in Thailand.MethodsA cross-sectional survey was conducted among all 658 dental undergraduates in Mahidol University, Thailand. Data was collected through a self-administered questionnaire, including the following information: (1) “Background and Demographics”: household income, hometown, residence during study and source(s) of any financial aid received; (2) “Living Expenses”: Living costs including food, transportation, rent, utility bills, and recreational expenses; (3) ”Education related expenses”: Including textbooks, stationeries, uniforms, and student activities fees. A cost-median was used as a baseline representation for the actual cost of each item. The mean differences of all expenses between groups before estimation was assessed by using the analysis of variance (ANOVA) method. The statistically significant differences were identified atp < 0.001.ResultsThe estimated adjusted cost of becoming a dentist in Thailand is THB1,265,027 (36,143.63 USD) for students living at home and THB1,823,027 (52,086.49 USD) for those renting accommodation. Students who rented accommodation incurred significantly higher yearly living expenses than those who were living at home. (p < 0.001). The majority of participants (78.4%) were in households having a middle-to-high socioeconomic status. Ninety-five percentages of the participants’ received 100% financial support from their families with no additional source of income, which reflects no real diversity in the socioeconomic background of Dental Degree students.ConclusionThe cost of a higher education Dental Degree in Thailand can be a significant barrier to entry and financial burden, especially for students from disadvantaged socioeconomic backgrounds. Government and Educational Policy makers need to pay more attention to this issue in order to provide equal opportunities for obtaining a University Dental Degree for all Thai students wishing to pursue this career path.
IRAK-M suppresses the activation of microglial NLRP3 inflammasome and GSDMD-mediated pyroptosis through inhibiting IRAK1 phosphorylation during experimental autoimmune encephalomyelitis
Authors: Wang Yuanyuan , Pei Shanshan , Liu Zhuhe , Ding Yuewen , Qian Tinglin , Wen Haixia , Hsu Ssu-Wei , Zhou Zheyi , Zhang Jun , Wang Honghao 
Published: February 2023

AbstractThe activation of the NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome triggers pyroptosis proinflammatory cell death in experimental autoimmune encephalomyelitis (EAE). However, the underlying mechanisms of the inflammatory processes of microglia in EAE remain unclear. Our previous studies suggested that interleukin-1 receptor-associated kinase (IRAK)-M down-regulates the toll-like receptor 4/interleukin-1 receptor signaling pathway. Here, we used IRAK-M knockout (IRAK-M−/−) mice and their microglia to dissect the role of IRAK-M in EAE. We found that deletion of IRAK-M increased the incidence rate and exacerbated the clinical symptoms in EAE mice. We then found that IRAK-M deficiency promoted the activation of microglia, activated NLRP3 inflammasomes, and enhanced GSDMD-mediated pyroptosis in the microglia of EAE. In contrast, over-expression of IRAK-M exerted inhibitory effects on neuroinflammation, NLRP3 activation, and pyroptosis. Moreover, IRAK-M deficiency enhanced the phosphorylation of IRAK1, while IRAK-M over-expression downregulated the level of phosphorylated IRAK1. Finally, we found upregulated binding of IRAK1 and TNF receptor-associated factor 6 (TRAF6) in IRAK-M−/− EAE mice compared to WT mice, which was blocked in AAVIRAK-M EAE mice. Our study reveals a complex signaling network of IRAK-M, which negatively regulates microglial NLRP3 inflammasomes and pyroptosis by inhibiting IRAK1 phosphorylation during EAE. These findings suggest a potential target for the novel therapeutic approaches of multiple sclerosis (MS)/EAE and NLRP3-related inflammatory diseases.
UBE2E2 enhances Snail-mediated epithelial-mesenchymal transition and Nrf2-mediated antioxidant activity in ovarian cancer
Authors: Hong Xiaoling , Ma Ning , Li Danjie , Zhang Mengwen , Dong Wenqiuzi , Huang Jie , Ci Xinxin , Zhang Songling 
Published: February 2023

AbstractDissemination of ovarian cancer (OvCa) cells can lead to inoperable metastatic lesions in the bowel and omentum, which have a poor prognosis despite surgical and chemotherapeutical options. A better understanding of the mechanisms underlying metastasis is urgently needed. In this study, bioinformatics analyses revealed that UBE2E2, a less-studied ubiquitin (Ub)-conjugating enzyme (E2), was upregulated in OvCa and was associated with poor prognosis. Subsequently, we performed western blot analysis and IHC staining with 88 OvCa and 26 normal ovarian tissue samples, which further confirmed that UBE2E2 protein is highly expressed in OvCa tissue but weakly expressed in normal tissue. Furthermore, the silencing of UBE2E2 blocked OvCa cell migration, epithelial-mesenchymal transition (EMT) and metastasis in vitro, whereas UBE2E2 overexpression exerted the opposite effects. Mechanistically, UBE2E2 promoted p62 accumulation and increased the activity of the Nrf2-antioxidant response element (ARE) system, which ultimately activated the Snail signaling pathway by inhibiting the ubiquitin-mediated degradation of Snail. Additionally, co-IP and immunofluorescence demonstrated that a direct interaction exists between UBE2E2 and Nrf2, and the N-terminal of UBE2E2 (residues 1-52) is required and sufficient for its interaction with Nrf2 protein. Mutations in the active site cysteine (Cys139) impaired both the function and cellular distribution of UBE2E2. More importantly, the deletion of UBE2E2 reduced tumorigenicity and metastasis in xenograft OvCa mouse models. Taken together, our findings reveal the role of the UBE2E2-Nrf2-p62-Snail signaling axis in OvCa and thus provides novel therapeutic targets for the prevention of OvCa metastasis.
MEK1 drives oncogenic signaling and interacts with PARP1 for genomic and metabolic homeostasis in malignant pleural mesothelioma
Authors: Yang Haitang , Gao Yanyun , Xu Duo , Xu Ke , Liang Shun-Qing , Yang Zhang , Scherz Amina , Hall Sean R. R. , Forster Stefan , Berezowska Sabina , Yao Feng , Ochsenbein Adrian F. , Marti Thomas M. , Kocher Gregor J. , Schmid Ralph A. , Dorn Patrick , Peng Ren-Wang 
Published: February 2023

AbstractMalignant pleural mesothelioma (MPM) is a lethal malignancy etiologically caused by asbestos exposure, for which there are few effective treatment options. Although asbestos carcinogenesis is associated with reactive oxygen species (ROS), the bona fide oncogenic signaling pathways that regulate ROS homeostasis and bypass ROS-evoked apoptosis in MPM are poorly understood. In this study, we demonstrate that the mitogen-activated protein kinase (MAPK) pathway RAS-RAF-MEK-ERK is hyperactive and a molecular driver of MPM, independent of histological subtypes and genetic heterogeneity. Suppression of MAPK signaling by clinically approved MEK inhibitors (MEKi) elicits PARP1 to protect MPM cells from the cytotoxic effects of MAPK pathway blockage. Mechanistically, MEKi induces impairment of homologous recombination (HR) repair proficiency and mitochondrial metabolic activity, which is counterbalanced by pleiotropic PARP1. Consequently, the combination of MEK with PARP inhibitors enhances apoptotic cell death in vitro and in vivo that occurs through coordinated upregulation of cytotoxic ROS in MPM cells, suggesting a mechanism-based, readily translatable strategy to treat this daunting disease. Collectively, our studies uncover a previously unrecognized scenario that hyperactivation of the MAPK pathway is an essential feature of MPM and provide unprecedented evidence that MAPK signaling cooperates with PARP1 to homeostatically maintain ROS levels and escape ROS-mediated apoptosis.
Role of NAT10-mediated ac4C-modified HSP90AA1 RNA acetylation in ER stress-mediated metastasis and lenvatinib resistance in hepatocellular carcinoma
Authors: Pan Zhipeng , Bao Yawei , Hu Mengyao , Zhu Yue , Tan Chaisheng , Fan Lulu , Yu Hanqing , Wang Anqi , Cui Jie , Sun Guoping 
Published: February 2023

AbstractEmerging evidence showed that epigenetic regulation plays important role in the pathogenesis of HCC.N4-acetocytidine (ac4C) was an acetylation chemical modification of mRNA, and NAT10 is reported to regulate ac4C modification and enhance endoplasmic reticulum stress (ERS) in tumor metastasis. Here, we report a novel mechanism by which NAT10-mediated mRNA ac4C-modified HSP90AA1 regulates metastasis and tumor resistance in ERS of HCC. Immunohistochemical, bioinformatics analyses, and in vitro and in vivo experiments, e.g., acRIP-Seq, RNA-Seq, and double luciferase reporter experiment, were employed to investigate the effect of NAT10 on metastasis and drug resistance in HCC. The increased expression of NAT10 was associated with HCC risk and poor prognosis. Cell and animal experiments showed that NAT10 enhanced the metastasis ability and apoptosis resistance of HCC cells in ERS and ERS state. NAT10 could upregulate the modification level of HSP90AA1 mRNA ac4C, maintain the stability of HSP90AA1, and upregulate the expression of HSP90AA1, which further promotes the metastasis of ERS hepatoma cells and the resistance to apoptosis of Lenvatinib. This study proposes a novel mechanism by which NAT10-mediated mRNA ac4C modification regulates tumor metastasis. In addition, we demonstrated the regulatory effect of NAT10-HSP90AA1 on metastasis and drug resistance of ERS in HCC cells.
Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death
Authors: Arif Waqar , Mathur Bhoomika , Saikali Michael F. , Chembazhi Ullas V. , Toohill Katelyn , Song You Jin , Hao Qinyu , Karimi Saman , Blue Steven M. , Yee Brian A. , Van Nostrand Eric L. , Bangru Sushant , Guzman Grace , Yeo Gene W. , Prasanth Kannanganattu V. , Anakk Sayeepriyadarshini , Cummins Carolyn L. , Kalsotra Auinash 
Published: February 2023

AbstractRegulation of RNA processing contributes profoundly to tissue development and physiology. Here, we report that serine-arginine-rich splicing factor 1 (SRSF1) is essential for hepatocyte function and survival. Although SRSF1 is mainly known for its many roles in mRNA metabolism, it is also crucial for maintaining genome stability. We show that acute liver damage in the setting of targeted SRSF1 deletion in mice is associated with the excessive formation of deleterious RNA–DNA hybrids (R-loops), which induce DNA damage. Combining hepatocyte-specific transcriptome, proteome, and RNA binding analyses, we demonstrate that widespread genotoxic stress following SRSF1 depletion results in global inhibition of mRNA transcription and protein synthesis, leading to impaired metabolism and trafficking of lipids. Lipid accumulation in SRSF1-deficient hepatocytes is followed by necroptotic cell death, inflammation, and fibrosis, resulting in NASH-like liver pathology. Importantly, SRSF1-depleted human liver cancer cells recapitulate this pathogenesis, illustrating a conserved and fundamental role for SRSF1 in preserving genome integrity and tissue homeostasis. Thus, our study uncovers how the accumulation of detrimental R-loops impedes hepatocellular gene expression, triggering metabolic derangements and liver damage.
The impacts of SARS-CoV-2 vaccine dose separation and targeting on the COVID-19 epidemic in England
Authors: Keeling Matt J. , Moore Samuel , Penman Bridget S. , Hill Edward M. 
Published: February 2023

AbstractIn late 2020, the JCVI (the Joint Committee on Vaccination and Immunisation, which provides advice to the Department of Health and Social Care, England) made two important recommendations for the initial roll-out of the COVID-19 vaccine. The first was that vaccines should be targeted to older and vulnerable people, with the aim of maximally preventing disease rather than infection. The second was to increase the interval between first and second doses from 3 to 12 weeks. Here, we re-examine these recommendations through a mathematical model of SARS-CoV-2 infection in England. We show that targeting the most vulnerable had the biggest immediate impact (compared to targeting younger individuals who may be more responsible for transmission). The 12-week delay was also highly beneficial, estimated to have averted between 32-72 thousand hospital admissions and 4-9 thousand deaths over the first ten months of the campaign (December 2020–September 2021) depending on the assumed interaction between dose interval and efficacy.
Higher rank chirality and non-Hermitian skin effect in a topolectrical circuit
Authors: Zhu Penghao , Sun Xiao-Qi , Hughes Taylor L. , Bahl Gaurav 
Published: February 2023

AbstractWhile chirality imbalances are forbidden in conventional lattice systems, non-Hermiticity can effectively avoid the chiral-doubling theorem to facilitate 1D chiral dynamics. Indeed, such systems support unbalanced unidirectional flows that can lead to the localization of an extensive number of states at the boundary, known as the non-Hermitian skin effect (NHSE). Recently, a generalized (rank-2) chirality describing a 2D robust gapless mode with dispersion ω = kxky has been introduced in crystalline systems. Here we demonstrate that rank-2 chirality imbalances can be established in a non-Hermitian (NH) lattice system leading to momentum-resolved chiral dynamics, and a rank-2 NHSE where there are both edge- and corner-localized skin modes. We then experimentally test this phenomenology in a 2-dimensional topolectric circuit that implements a NH Hamiltonian with a long-lived rank-2 chiral mode. Using impedance measurements, we confirm the rank-2 NHSE in this system, and its manifestation in the predicted skin modes and a highly unusual momentum-position locking response. Our investigation demonstrates a circuit-based path to exploring higher-rank chiral physics, with potential applications in systems where momentum resolution is necessary, e.g., in beamformers and non-reciprocal devices.
A conformational switch in clathrin light chain regulates lattice structure and endocytosis at the plasma membrane of mammalian cells
Authors: Obashi Kazuki , Sochacki Kem A. , Strub Marie-Paule , Taraska Justin W. 
Published: February 2023

AbstractConformational changes in endocytic proteins are regulators of clathrin-mediated endocytosis. Three clathrin heavy chains associated with clathrin light chains (CLC) assemble into triskelia that link into a geometric lattice that curves to drive endocytosis. Structural changes in CLC have been shown to regulate triskelia assembly in solution, yet the nature of these changes, and their effects on lattice growth, curvature, and endocytosis in cells are unknown. Here, we develop a new correlative fluorescence resonance energy transfer (FRET) and platinum replica electron microscopy method, named FRET-CLEM. With FRET-CLEM, we measure conformational changes in clathrin at thousands of individual morphologically distinct clathrin-coated structures. We discover that the N-terminus of CLC repositions away from the plasma membrane and triskelia vertex as coats curve. Preventing this conformational switch with chemical tools increases lattice sizes and inhibits endocytosis. Thus, a specific conformational switch in the light chain regulates lattice curvature and endocytosis in mammalian cells.
Long-term platinum-based drug accumulation in cancer-associated fibroblasts promotes colorectal cancer progression and resistance to therapy
Authors: Linares Jenniffer , Sallent-Aragay Anna , Badia-Ramentol Jordi , Recort-Bascuas Alba , Méndez Ana , Manero-Rupérez Noemí , Re Daniele Lo , Rivas Elisa I. , Guiu Marc , Zwick Melissa , Iglesias Mar , Martinez-Ciarpaglini Carolina , Tarazona Noelia , Varese Monica , Hernando-Momblona Xavier , Cañellas-Socias Adrià , Orrillo Mayra , Garrido Marta , Saoudi Nadia , Elez Elena , Navarro Pilar , Tabernero Josep , Gomis Roger R. , Batlle Eduard , Pisonero Jorge , Cervantes Andres , Montagut Clara , Calon Alexandre 
Published: February 2023

AbstractA substantial proportion of cancer patients do not benefit from platinum-based chemotherapy (CT) due to the emergence of drug resistance. Here, we apply elemental imaging to the mapping of CT biodistribution after therapy in residual colorectal cancer and achieve a comprehensive analysis of the genetic program induced by oxaliplatin-based CT in the tumor microenvironment. We show that oxaliplatin is largely retained by cancer-associated fibroblasts (CAFs) long time after the treatment ceased. We determine that CT accumulation in CAFs intensifies TGF-beta activity, leading to the production of multiple factors enhancing cancer aggressiveness. We establish periostin as a stromal marker of chemotherapeutic activity intrinsically upregulated in consensus molecular subtype 4 (CMS4) tumors and highly expressed before and/or after treatment in patients unresponsive to therapy. Collectively, our study underscores the ability of CT-retaining CAFs to support cancer progression and resistance to treatment.