bluuebunny/crossref_metadata_2025 huggingface dataset:
Upper Cretaceous–Paleocene Magnetostratigraphy of the Longmenshan Foreland Basin and Its Implications for the Tectonic Deformation of the Longmenshan Fault Zone
Authors: Hou Lifu , Pei Junling , Cai Yuhang , Zhou Zaizheng , Tong Yabo , Zhao Yue
Published: February 2023

Knowledge of the history of the tectonic deformation of the eastern edge of Tibet is important for understanding the evolution of the entire Tibetan Plateau; however, the corresponding tectonic deformation process remains controversial. We conducted a detailed rock magnetic and magnetostratigraphic study of the Cretaceous Jiaguan and Guankou Formations (the Jinmenguan section) within the Longmenshan foreland basin on the eastern edge of Tibetan Plateau. The high‐temperature remanence components separated after thermal demagnetization passed the A‐class reversal test, Bootstrap Cartesian coordinate test, and fold test, at the 95% confidence level. The resulting magnetostratigraphy constrains the age range of the Jinmenguan section to 128.0–64.1 Ma, and that of the Jiaguan Formation to 128.0–83.6 Ma. The resulting chronology identifies two phases of rapid sedimentation (128.0–124.1, 68.8–64.1 Ma) that constrain two phases of tectonic uplift in the Longmenshan Fault Zone on the eastern margin of Tibet during the Cretaceous–early Cenozoic. Our findings suggest that the stress field generated by the subduction and closure of the Bangong‐Nujiang Ocean had already been transferred to the eastern edge of the Tibet in the Cretaceous (at ∼128 Ma).
How to Build a Climate-Resilient Water Supply
Authors: Fritts Rachel
Published: February 2023

Scientists developed a new model to help water utility companies minimize weather-based disruptions to clean water access.
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

Cancer 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

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

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

Objectives

To determine the overall estimated financial impact and related expenses incurred over the duration of the undergraduate Dental Degree in Thailand.

Methods

A 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.

Results

The 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.

Conclusion

The 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

The 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

Dissemination 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

Malignant 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

Emerging 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

Regulation 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

In 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

While 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

Conformational 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

A 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.
Ultrathin positively charged electrode skin for durable anion-intercalation battery chemistries
Authors: Sabaghi Davood , Wang Zhiyong , Bhauriyal Preeti , Lu Qiongqiong , Morag Ahiud , Mikhailovia Daria , Hashemi Payam , Li Dongqi , Neumann Christof , Liao Zhongquan , Dominic Anna Maria , Nia Ali Shaygan , Dong Renhao , Zschech Ehrenfried , Turchanin Andrey , Heine Thomas , Yu Minghao , Feng Xinliang
Published: February 2023

The anion-intercalation chemistries of graphite have the potential to construct batteries with promising energy and power breakthroughs. Here, we report the use of an ultrathin, positively charged two-dimensional poly(pyridinium salt) membrane (C2DP) as the graphite electrode skin to overcome the critical durability problem. Large-area C2DP enables the conformal coating on the graphite electrode, remarkably alleviating the electrolyte. Meanwhile, the dense face-on oriented single crystals with ultrathin thickness and cationic backbones allow C2DP with high anion-transport capability and selectivity. Such desirable anion-transport properties of C2DP prevent the cation/solvent co-intercalation into the graphite electrode and suppress the consequent structure collapse. An impressive PF6−-intercalation durability is demonstrated for the C2DP-covered graphite electrode, with capacity retention of 92.8% after 1000 cycles at 1 C and Coulombic efficiencies of > 99%. The feasibility of constructing artificial ion-regulating electrode skins with precisely customized two-dimensional polymers offers viable means to promote problematic battery chemistries.
Emergence of chaos in a compartmentalized catalytic reaction nanosystem
Authors: Raab Maximilian , Zeininger Johannes , Suchorski Yuri , Tokuda Keita , Rupprechter Günther
Published: February 2023

In compartmentalized systems, chemical reactions may proceed in differing ways even in adjacent compartments. In compartmentalized nanosystems, the reaction behaviour may deviate from that observed on the macro- or mesoscale. In situ studies of processes in such nanosystems meet severe experimental challenges, often leaving the field to theoretical simulations. Here, a rhodium nanocrystal surface consisting of different nm-sized nanofacets is used as a model of a compartmentalized reaction nanosystem. Using field emission microscopy, different reaction modes are observed, including a transition to spatio-temporal chaos. The transitions between different modes are caused by variations of the hydrogen pressure modifying the strength of diffusive coupling between individual nanofacets. Microkinetic simulations, performed for a network of 52 coupled oscillators, reveal the origins of the different reaction modes. Since diffusive coupling is characteristic for many living and non-living compartmentalized systems, the current findings may be relevant for a wide class of reaction systems.
Hybrid assembly of polymeric nanofiber network for robust and electronically conductive hydrogels
Authors: He Huimin , Li Hao , Pu Aoyang , Li Wenxiu , Ban Kiwon , Xu Lizhi
Published: February 2023

Electroconductive hydrogels have been applied in implantable bioelectronics, tissue engineering platforms, soft actuators, and other emerging technologies. However, achieving high conductivity and mechanical robustness remains challenging. Here we report an approach to fabricating electroconductive hydrogels based on the hybrid assembly of polymeric nanofiber networks. In these hydrogels, conducting polymers self-organize into highly connected three dimensional nanostructures with an ultralow threshold (~1 wt%) for electrical percolation, assisted by templating effects from aramid nanofibers, to achieve high electronic conductivity and structural robustness without sacrificing porosity or water content. We show that a hydrogel composed of polypyrrole, aramid nanofibers and polyvinyl alcohol achieves conductivity of ~80 S cm−1, mechanical strength of ~9.4 MPa and stretchability of ~36%. We show that patterned conductive nanofiber hydrogels can be used as electrodes and interconnects with favorable electrochemical impedance and charge injection capacity for electrophysiological applications. In addition, we demonstrate that cardiomyocytes cultured on soft and conductive nanofiber hydrogel substrates exhibit spontaneous and synchronous beating, suggesting opportunities for the development of advanced implantable devices and tissue engineering technologies.
Classification of time-reversal-invariant crystals with gauge structures
Authors: Chen Z. Y. , Zhang Zheng , Yang Shengyuan A. , Zhao Y. X.
Published: February 2023

A peculiar feature of quantum states is that they may embody so-called projective representations of symmetries rather than ordinary representations. Projective representations of space groups-the defining symmetry of crystals-remain largely unexplored. Despite recent advances in artificial crystals, whose intrinsic gauge structures necessarily require a projective description, a unified theory is yet to be established. Here, we establish such a unified theory by exhaustively classifying and representing all 458 projective symmetry algebras of time-reversal-invariant crystals from 17 wallpaper groups in two dimensions-189 of which are algebraically non-equivalent. We discover three physical signatures resulting from projective symmetry algebras, including the shift of high-symmetry momenta, an enforced nontrivial Zak phase, and a spinless eight-fold nodal point. Our work offers a theoretical foundation for the field of artificial crystals and opens the door to a wealth of topological states and phenomena beyond the existing paradigms.
Intrafusal-fiber LRP4 for muscle spindle formation and maintenance in adult and aged animals
Authors: Cao Rangjuan , Chen Peng , Wang Hongsheng , Jing Hongyang , Zhang Hongsheng , Xing Guanglin , Luo Bin , Pan Jinxiu , Yu Zheng , Xiong Wen-Cheng , Mei Lin
Published: February 2023

Proprioception is sensed by muscle spindles for precise locomotion and body posture. Unlike the neuromuscular junction (NMJ) for muscle contraction which has been well studied, mechanisms of spindle formation are not well understood. Here we show that sensory nerve terminals are disrupted by the mutation ofLrp4, a gene required for NMJ formation; inducible knockout ofLrp4in adult mice impairs sensory synapses and movement coordination, suggesting that LRP4 is required for spindle formation and maintenance. LRP4 is critical to the expression of Egr3 during development; in adult mice, it interacts in trans with APP and APLP2 on sensory terminals. Finally, spindle sensory endings and function are impaired in aged mice, deficits that could be diminished by LRP4 expression. These observations uncovered LRP4 as an unexpected regulator of muscle spindle formation and maintenance in adult and aged animals and shed light on potential pathological mechanisms of abnormal muscle proprioception.
The cytoplasmic synthesis and coupled membrane translocation of eukaryotic polyphosphate by signal-activated VTC complex
Authors: Guan Zeyuan , Chen Juan , Liu Ruiwen , Chen Yanke , Xing Qiong , Du Zhangmeng , Cheng Meng , Hu Jianjian , Zhang Wenhui , Mei Wencong , Wan Beijing , Wang Qiang , Zhang Jie , Cheng Peng , Cai Huanyu , Cao Jianbo , Zhang Delin , Yan Junjie , Yin Ping , Hothorn Michael , Liu Zhu
Published: February 2023

Inorganic polyphosphate (polyP) is an ancient energy metabolite and phosphate store that occurs ubiquitously in all organisms. The vacuolar transporter chaperone (VTC) complex integrates cytosolic polyP synthesis from ATP and polyP membrane translocation into the vacuolar lumen. In yeast and in other eukaryotes, polyP synthesis is regulated by inositol pyrophosphate (PP-InsP) nutrient messengers, directly sensed by the VTC complex. Here, we report the cryo-electron microscopy structure of signal-activated VTC complex at 3.0 Å resolution. Baker’s yeast VTC subunits Vtc1, Vtc3, and Vtc4 assemble into a 3:1:1 complex. Fifteen trans-membrane helices form a novel membrane channel enabling the transport of newly synthesized polyP into the vacuolar lumen. PP-InsP binding orients the catalytic polymerase domain at the entrance of the trans-membrane channel, both activating the enzyme and coupling polyP synthesis and membrane translocation. Together with biochemical and cellular studies, our work provides mechanistic insights into the biogenesis of an ancient energy metabolite.
Multilingual translation for zero-shot biomedical classification using BioTranslator
Authors: Xu Hanwen , Woicik Addie , Poon Hoifung , Altman Russ B. , Wang Sheng
Published: February 2023

Existing annotation paradigms rely on controlled vocabularies, where each data instance is classified into one term from a predefined set of controlled vocabularies. This paradigm restricts the analysis to concepts that are known and well-characterized. Here, we present the novel multilingual translation method BioTranslator to address this problem. BioTranslator takes a user-written textual description of a new concept and then translates this description to a non-text biological data instance. The key idea of BioTranslator is to develop a multilingual translation framework, where multiple modalities of biological data are all translated to text. We demonstrate how BioTranslator enables the identification of novel cell types using only a textual description and how BioTranslator can be further generalized to protein function prediction and drug target identification. Our tool frees scientists from limiting their analyses within predefined controlled vocabularies, enabling them to interact with biological data using free text.
Mangrove reforestation provides greater blue carbon benefit than afforestation for mitigating global climate change
Authors: Song Shanshan , Ding Yali , Li Wei , Meng Yuchen , Zhou Jian , Gou Ruikun , Zhang Conghe , Ye Shengbin , Saintilan Neil , Krauss Ken W. , Crooks Stephen , Lv Shuguo , Lin Guanghui
Published: February 2023

Significant efforts have been invested to restore mangrove forests worldwide through reforestation and afforestation. However, blue carbon benefit has not been compared between these two silvicultural pathways at the global scale. Here, we integrated results from direct field measurements of over 370 restoration sites around the world to show that mangrove reforestation (reestablishing mangroves where they previously colonized) had a greater carbon storage potential per hectare than afforestation (establishing mangroves where not previously mangrove). Greater carbon accumulation was mainly attributed to favorable intertidal positioning, higher nitrogen availability, and lower salinity at most reforestation sites. Reforestation of all physically feasible areas in the deforested mangrove regions of the world could promote the uptake of 671.5–688.8 Tg CO2-eq globally over a 40-year period, 60% more than afforesting the same global area on tidal flats (more marginal sites). Along with avoiding conflicts of habitat conversion, mangrove reforestation should be given priority when designing nature-based solutions for mitigating global climate change.
Leaf transformation for efficient random integration and targeted genome modification in maize and sorghum
Authors: Wang Ning , Ryan Larisa , Sardesai Nagesh , Wu Emily , Lenderts Brian , Lowe Keith , Che Ping , Anand Ajith , Worden Andrew , van Dyk Daleen , Barone Pierluigi , Svitashev Sergei , Jones Todd , Gordon-Kamm William
Published: February 2023

Transformation in grass species has traditionally relied on immature embryos and has therefore been limited to a few major Poaceae crops. Other transformation explants, including leaf tissue, have been explored but with low success rates, which is one of the major factors hindering the broad application of genome editing for crop improvement. Recently, leaf transformation using morphogenic genes Wuschel2 (Wus2) and Babyboom (Bbm) has been successfully used for Cas9-mediated mutagenesis, but complex genome editing applications, requiring large numbers of regenerated plants to be screened, remain elusive. Here we demonstrate that enhanced Wus2/Bbm expression substantially improves leaf transformation in maize and sorghum, allowing the recovery of plants with Cas9-mediated gene dropouts and targeted gene insertion. Moreover, using a maize-optimized Wus2/Bbm construct, embryogenic callus and regenerated plantlets were successfully produced in eight species spanning four grass subfamilies, suggesting that this may lead to a universal family-wide method for transformation and genome editing across the Poaceae.
A scrub typhus vaccine presents a challenging unmet need
Authors: Walker David H. , Mendell Nicole L.
Published: February 2023

Scrub typhus caused by the obligately intracellular bacterium, Orientia tsutsugamushi, is a major cause of life-threatening acute undifferentiated febrile illness in eastern Asia and the islands of the Western Pacific and Indian oceans. Since the estimation of an incidence of 1 million cases annually two decades ago, the number of cases has increased substantially in endemic regions, reappeared where the disease was forgotten, and spread northward. Trombiculid mites are both reservoir and vector. Despite 80 years of efforts to develop a vaccine, there is none. Protective immunity is mediated by antibodies and CD8 and CD4 T cells. Previous efforts have failed because of gaps in understanding immunity to O. tsutsugamushi, particularly the requirements for vaccine-induced immunity, lack of knowledge regarding immune memory in scrub typhus, and lack of attention to addressing the issue of cross-protection between strains. There are numerous strains of O. tsutsugamushi, and modestly durable immunity is strain-specific. Antibodies to the strain that caused infection are protective against challenges with the homologous strain but, despite reactivity with other immunodominant antigens, the immune serum does not protect against heterologous strains. Among the antigens detected by western immunoblot in immune sera (22-, 47-, 56-, 58-, and 110 kDa proteins), only the 56 kDa protein stimulates strong protection. This protein contains four hypervariable regions which are likely, on the basis of limited data, to be the targets of neutralizing antibodies. However, a method that definitively detects neutralizing antibody has yet to be developed. Only one study has used genomic data to pursue the discovery of protective antigens. Three conserved autotransporters were identified, and only immunization with ScaA provided protection against the homologous strain, but only 40% of animals were protected against challenge with a heterologous strain. A multiplex vaccine containing conformational antigens of the hypervariable regions of the 56 kDa protein of the strains of the greatest clinical and epidemiological importance, as well as conserved regions of the 56 kDa protein, ScaA, and other protective antigens identified by future genomic and bioinformatics methods should be developed and tested.
Genetic mapping of microbial and host traits reveals production of immunomodulatory lipids by Akkermansia muciniphila in the murine gut
Authors: Zhang Q. , Linke V. , Overmyer K. A. , Traeger L. L. , Kasahara K. , Miller I. J. , Manson D. E. , Polaske T. J. , Kerby R. L. , Kemis J. H. , Trujillo E. A. , Reddy T. R. , Russell J. D. , Schueler K. L. , Stapleton D. S. , Rabaglia M. E. , Seldin M. , Gatti D. M. , Keele G. R. , Pham D. T. , Gerdt J. P. , Vivas E. I. , Lusis A. J. , Keller M. P. , Churchill G. A. , Blackwell H. E. , Broman K. W. , Attie A. D. , Coon J. J. , Rey F. E.
Published: February 2023

The molecular bases of how host genetic variation impacts the gut microbiome remain largely unknown. Here we used a genetically diverse mouse population and applied systems genetics strategies to identify interactions between host and microbe phenotypes including microbial functions, using faecal metagenomics, small intestinal transcripts and caecal lipids that influence microbe–host dynamics. Quantitative trait locus (QTL) mapping identified murine genomic regions associated with variations in bacterial taxa; bacterial functions including motility, sporulation and lipopolysaccharide production and levels of bacterial- and host-derived lipids. We found overlapping QTL for the abundance of Akkermansia muciniphila and caecal levels of ornithine lipids. Follow-up in vitro and in vivo studies revealed that A. muciniphila is a major source of these lipids in the gut, provided evidence that ornithine lipids have immunomodulatory effects and identified intestinal transcripts co-regulated with these traits including Atf3, which encodes for a transcription factor that plays vital roles in modulating metabolism and immunity. Collectively, these results suggest that ornithine lipids are potentially important for A. muciniphila–host interactions and support the role of host genetics as a determinant of responses to gut microbes.
Deterministic generation of indistinguishable photons in a cluster state
Authors: Cogan Dan , Su Zu-En , Kenneth Oded , Gershoni David
Published: February 2023

Entanglement between particles is a basic concept of quantum sciences. The ability to produce entangled particles in a controllable manner is essential for any quantum technology. Entanglement between light particles (photons) is particularly crucial for quantum communication due to light’s non-interactive nature and long-lasting coherence. Resources producing entangled multiphoton cluster states will enable communication between remote quantum nodes, as the inbuilt redundancy of cluster photons allows for repeated local measurements—compensating for losses and probabilistic Bell measurements. For feasible applications, the cluster generation should be fast, deterministic and, most importantly, its photons indistinguishable, which will allow measurements and fusion of clusters by interfering photons. Here, using periodic excitation of a semiconductor quantum-dot-confined spin, we demonstrate a multi-indistinguishable photon cluster, featuring a continuously generated string of photons at deterministic gigahertz generation rates, and an optimized entanglement length of about ten photons. The indistinguishability of the photons opens up new possibilities for scaling up the cluster’s dimensionality by fusion, thus building graph states suited for measurement-based photonic quantum computers and all-photonic quantum repeaters.
An optimized bioluminescent substrate for non-invasive imaging in the brain
Authors: Su Yichi , Walker Joel R. , Hall Mary P. , Klein Mark A. , Wu Xiang , Encell Lance P. , Casey Kerriann M. , Liu Lan Xiang , Hong Guosong , Lin Michael Z. , Kirkland Thomas A.
Published: February 2023

Bioluminescence imaging (BLI) allows non-invasive visualization of cells and biochemical events in vivo and thus has become an indispensable technique in biomedical research. However, BLI in the central nervous system remains challenging because luciferases show relatively poor performance in the brain with existing substrates. Here, we report the discovery of a NanoLuc substrate with improved brain performance, cephalofurimazine (CFz). CFz paired with Antares luciferase produces greater than 20-fold more signal from the brain than the standard combination of d-luciferin with firefly luciferase. At standard doses, Antares–CFz matches AkaLuc–AkaLumine/TokeOni in brightness, while occasional higher dosing of CFz can be performed to obtain threefold more signal. CFz should allow the growing number of NanoLuc-based indicators to be applied to the brain with high sensitivity. Using CFz, we achieve video-rate non-invasive imaging of Antares in brains of freely moving mice and demonstrate non-invasive calcium imaging of sensory-evoked activity in genetically defined neurons.
A molecular switch modulates assembly and host factor binding of the HIV-1 capsid
Authors: Schirra Randall T. , dos Santos Nayara F. B. , Zadrozny Kaneil K. , Kucharska Iga , Ganser-Pornillos Barbie K. , Pornillos Owen
Published: February 2023

The HIV-1 capsid is a fullerene cone made of quasi-equivalent hexamers and pentamers of the viral CA protein. Typically, quasi-equivalent assembly of viral capsid subunits is controlled by a molecular switch. Here, we identify a Thr-Val-Gly-Gly motif that modulates CA hexamer/pentamer switching by folding into a 310 helix in the pentamer and random coil in the hexamer. Manipulating the coil/helix configuration of the motif allowed us to control pentamer and hexamer formation in a predictable manner, thus proving its function as a molecular switch. Importantly, the switch also remodels the common binding site for host factors that are critical for viral replication and the new ultra-potent HIV-1 inhibitor lenacapavir. This study reveals that a critical assembly element also modulates the post-assembly and viral replication functions of the HIV-1 capsid and provides new insights on capsid function and inhibition.
Conserved miR-370-3p/BMP-7 axis regulates the phenotypic change of human vascular smooth muscle cells
Authors: Kim Yerin , Yu Namhee , Jang Ye Eun , Lee Eunkyung , Jung Yeonjoo , Lee Doo Jae , Taylor W. Robert , Jo Hanjoong , Kim Jaesang , Lee Sanghyuk , Kang Sang Won
Published: February 2023

Endothelial dysfunction and inflammatory immune response trigger dedifferentiation of vascular smooth muscle cells (SMCs) from contractile to synthetic phenotype and initiate arterial occlusion. However, the complex vascular remodeling process playing roles in arterial occlusion initiation is largely unknown. We performed bulk sequencing of small and messenger RNAs in a rodent arterial injury model. Bioinformatic data analyses reveal that six miRNAs are overexpressed in injured rat carotids as well as synthetic-type human vascular SMCs. In vitro cell-based assays show that four miRNAs (miR-130b-5p, miR-132-3p, miR-370-3p, and miR-410-3p) distinctly regulate the proliferation of and monocyte adhesion to the vascular SMCs. Individual inhibition of the four selected miRNAs strongly prevents the neointimal hyperplasia in the injured rat carotid arteries. Mechanistically, miR-132-3p and miR-370-3p direct the cell cycle progression, triggering SMC proliferation. Gene ontology analysis of mRNA sequencing data consistently reveal that the miRNA targets include gene clusters that direct proliferation, differentiation, and inflammation. Notably, bone morphogenic protein (BMP)-7 is a prominent target gene of miR-370-3p, and it regulates vascular SMC proliferation in cellular and animal models. Overall, this study first reports that the miR-370-3p/BMP-7 axis determines the vascular SMC phenotype in both rodent and human systems.