bluuebunny/crossref_metadata_2025 huggingface dataset:
Vemurafenib inhibits necroptosis in normal and pathological conditions as a RIPK1 antagonist
Authors: Sun Mayu , Ma Xueqi , Mu Wei , Li Haonan , Zhao Xiaoming , Zhu Tengfei , Li Jingquan , Yang Yongliang , Zhang Haibing , Ba Qian , Wang Hui
Published: August 2023

Necroptosis, a programmed cell death with necrotic-like morphology, has been recognized as an important driver in various inflammatory diseases. Inhibition of necroptosis has shown potential promise in the therapy of multiple human diseases. However, very few necroptosis inhibitors are available for clinical use as yet. Here, we identified an FDA-approved anti-cancer drug, Vemurafenib, as a potent inhibitor of necroptosis. Through direct binding, Vemurafenib blocked the kinase activity of receptor-interacting protein kinases 1 (RIPK1), impeded the downstream signaling and necrosome complex assembly, and inhibited necroptosis. Compared with Necrostain-1, Vemurafenib stabilized RIPK1 in an inactive DLG-out conformation by occupying a distinct allosteric hydrophobic pocket. Furthermore, pretreatment with Vemurafenib provided strong protection against necroptosis-associated diseases in vivo. Altogether, our results demonstrate that Vemurafenib is an effective RIPK1 antagonist and provide rationale and preclinical evidence for the potential application of approved drug in necroptosis-related diseases.
Clinical-mediated discovery of pyroptosis in CD8+ T cell and NK cell reveals melanoma heterogeneity by single-cell and bulk sequence
Authors: Zhang Ying , Bai Yun , Ma Xiao-Xuan , Song Jian-Kun , Luo Yue , Fei Xiao-Ya , Ru Yi , Luo Ying , Jiang Jing-Si , Zhang Zhan , Yang Dan , Xue Ting-Ting , Zhang Hui-Ping , Liu Tai-Yi , Xiang Yan-Wei , Kuai Le , Liu Ye-Qiang , Li Bin
Published: August 2023

Histologically, melanoma tissues had fewer positive cells percentage of pyroptosis-related genes (PRGs), GZMA, GSDMB, NLRP1, IL18, and CHMP4A in epidermal than in normal skin. Pyroptosis, a new frontier in cancer, affects the tumor microenvironment and tumor immunotherapy. Nevertheless, the role of pyroptosis remains controversial, which reason is partly due to the heterogeneity of the cellular composition in melanoma. In this study, we present a comprehensive analysis of the single-cell transcriptome landscape of pyroptosis in melanoma specimens. Our findings reveal dysregulation in the expression of PRGs, particularly in immune cells, such as CD8+ cells (representing CD8+ T cells) and CD57+ cells (representing NK cells). Additionally, the immunohistochemical and multiplex immunofluorescence staining experiments results further confirmed GZMA+ cells and GSDMB+ cells were predominantly expressed in immune cells, especially in CD8 + T cells and NK cells. Melanoma specimens secreted a minimal presence of GZMA+ merged CD8+ T cells (0.11%) and GSDMB+ merged CD57+ cells (0.08%), compared to the control groups exhibiting proportions of 4.02% and 0.62%, respectively. The aforementioned findings indicate that a reduced presence of immune cells within tumors may play a role in diminishing the ability of pyroptosis, consequently posing a potential risk to the anti-melanoma properties. To quantify clinical relevance, we constructed a prognostic risk model and an individualized nomogram (C-index=0.58, P = 0.002), suggesting a potential role of PRGs in malignant melanoma prevention. In conclusion, our integrated single-cell and bulk RNA-seq analysis identified immune cell clusters and immune gene modules with experiment validation, contributing to our better understanding of pyroptosis in melanoma.
A HER2-targeting antibody-MMAE conjugate RC48 sensitizes immunotherapy in HER2-positive colon cancer by triggering the cGAS-STING pathway
Authors: Wu Xiaohan , Xu Lingyan , Li Xiaofei , Zhou Yirui , Han Xiao , Zhang Wei , Wang Weicheng , Guo Wenjie , Liu Wen , Xu Qiang , Gu Yanhong
Published: August 2023

Human epidermal growth factor receptor 2 (HER2) is a protein that is overexpressed in some types of cancer, including breast and urothelial cancer. Here we found that HER2 was present in a portion of colon cancer patients, raising the possibility of using anti-HER2 therapy. RC48, a novel antibody-drug conjugate (ADC) comprising cytotoxic monomethyl auristatin E (MMAE) and an anti-HER2 antibody tethered via a linker, showed a comparable therapeutic effect in both HER2 low expressed (IHC2+/FISH- or IHC+) and high expressed urothelial cancer patients. In vitro studies using colon cancer cell lines showed that RC48 effectively impeded the proliferation of HER2-positive cells, indicating its potential as a treatment for HER2-positive colon cancer. Mechanism study showed that RC48 not only induces cell cycle arrest but also disrupts HER2-mediated restain of cGAS-STING signaling, potentially activating an immune response against the cancer cells. The administration of RC48 significantly reduced the growth of HER2-positive colon cancer and made HER2-positive colon cancer cells more susceptible to immunotherapy. The results of our study will contribute to determining the feasibility of RC48 as a therapeutic option for HER2-positive colon cancer.
Expression of Cyclin E1 in hepatic stellate cells is critical for the induction and progression of liver fibrosis and hepatocellular carcinoma in mice
Authors: Otto Julia , Verwaayen Anna , Penners Christian , Hundertmark Jana , Lin Cheng , Kallen Carina , Paffen Daniela , Otto Tobias , Berger Hilmar , Tacke Frank , Weiskirchen Ralf , Nevzorova Yulia A. , Bartneck Matthias , Trautwein Christian , Sonntag Roland , Liedtke Christian
Published: August 2023

Hepatocellular carcinoma (HCC) is one of the most severe malignancies with increasing incidence and limited treatment options. Typically, HCC develops during a multistep process involving chronic liver inflammation and liver fibrosis. The latter is characterized by the accumulation of extracellular matrix produced by Hepatic Stellate Cells (HSCs). This process involves cell cycle re-entry and proliferation of normally quiescent HSCs in an ordered sequence that is highly regulated by cyclins and associated cyclin-dependent kinases (CDKs) such as the Cyclin E1 (CCNE1)/CDK2 kinase complex. In the present study, we examined the role of Cyclin E1 (Ccne1) and Cdk2 genes in HSCs for liver fibrogenesis and hepatocarcinogenesis. To this end, we generated conditional knockout mice lacking Ccne1 or Cdk2 specifically in HSCs (Ccne1∆HSC or Cdk2∆HSC). Ccne1∆HSC mice showed significantly reduced liver fibrosis formation and attenuated HSC activation in the carbon tetrachloride (CCl4) model. In a combined model of fibrosis-driven hepatocarcinogenesis, Ccne1∆HSC mice revealed decreased HSC activation even after long-term observation and substantially reduced tumor load in the liver when compared to wild-type controls. Importantly, the deletion of Cdk2 in HSCs also resulted in attenuated liver fibrosis after chronic CCl4 treatment. Single-cell RNA sequencing revealed that only a small fraction of HSCs expressed Ccne1/Cdk2 at a distinct time point after CCl4 treatment. In summary, we provide evidence that Ccne1 expression in a small population of HSCs is sufficient to trigger extensive liver fibrosis and hepatocarcinogenesis in a Cdk2-dependent manner. Thus, HSC-specific targeting of Ccne1 or Cdk2 in patients with liver fibrosis and high risk for HCC development could be therapeutically beneficial.
Targeting ANXA7/LAMP5-mTOR axis attenuates spinal cord injury by inhibiting neuronal apoptosis via enhancing autophagy in mice
Authors: Li Na , Chen Lu , Zhao Xiaoqing , Gu Chi , Chang Yong , Feng Shiqing
Published: August 2023

Spinal cord injury (SCI) could lead to severe disabilities in motor and sensory functions, and cause a heavy burden on patient physiology and psychology due to lack of specific repair measures so far. ANXA7 is an annexin with Ca2+ -dependent GTPase activity, which were mainly expressed in neuron in spinal cord and downregulated significantly after SCI in mice. In our study, GTPase activity activation of ANXA7 plays the protective role in neuron after OGD/R through inhibiting neuron apoptosis, which mediated by enhancing autophagy via mTOR/TFEB pathway. We also discovered that ANXA7 has significant interaction with neural-specific lysosomal-associated membrane protein LAMP5, which together with ANXA7 regulates autophagy and apoptosis. Asp411 mutation of ANXA7 obviously impaired the interaction of ANXA7 and LAMP5 compared with the wild type. Furthermore, it was found that activation of ANXA7 could help to stabilize the protein expression of LAMP5. Overexpression of LAMP5 could attenuate the destruction of lysosomal acidic environment, inhibition of autophagy and activation of apoptosis caused by ANXA7 downregulation after OGD/R. We verified that injecting ANXA7 overexpression lentivirus and activation of ANXA7 both have significant repair effects on SCI mice by using CatWalk assay and immunohistochemistry staining. In summary, our findings clarify the new role of ANXA7 and LAMP5 in SCI, provided a new specific target of neuronal repair and discovered new molecular mechanisms of ANXA7 to regulate autophagy and apoptosis. Targeting ANXA7 may be a prospective therapeutic strategy for SCI in future.
Metal-mediated DNA strand displacement and molecular device operations based on base-pair switching of 5-hydroxyuracil nucleobases
Authors: Takezawa Yusuke , Mori Keita , Huang Wei-En , Nishiyama Kotaro , Xing Tong , Nakama Takahiro , Shionoya Mitsuhiko
Published: August 2023

Rational design of self-assembled DNA nanostructures has become one of the fastest-growing research areas in molecular science. Particular attention is focused on the development of dynamic DNA nanodevices whose configuration and function are regulated by specific chemical inputs. Herein, we demonstrate the concept of metal-mediated base-pair switching to induce inter- and intramolecular DNA strand displacement in a metal-responsive manner. The 5-hydroxyuracil (UOH) nucleobase is employed as a metal-responsive unit, forming both a hydrogen-bonded UOH–A base pair and a metal-mediated UOH–GdIII–UOH base pair. Metal-mediated strand displacement reactions are demonstrated under isothermal conditions based on the base-pair switching between UOH–A and UOH–GdIII–UOH. Furthermore, metal-responsive DNA tweezers and allosteric DNAzymes are developed as typical models for DNA nanodevices simply by incorporating UOH bases into the sequence. The metal-mediated base-pair switching will become a versatile strategy for constructing stimuli-responsive DNA nanostructures, expanding the scope of dynamic DNA nanotechnology.
Structural basis of peptidoglycan synthesis by E. coli RodA-PBP2 complex
Authors: Nygaard Rie , Graham Chris L. B. , Belcher Dufrisne Meagan , Colburn Jonathan D. , Pepe Joseph , Hydorn Molly A. , Corradi Silvia , Brown Chelsea M. , Ashraf Khuram U. , Vickery Owen N. , Briggs Nicholas S. , Deering John J. , Kloss Brian , Botta Bruno , Clarke Oliver B. , Columbus Linda , Dworkin Jonathan , Stansfeld Phillip J. , Roper David I. , Mancia Filippo
Published: August 2023

Peptidoglycan (PG) is an essential structural component of the bacterial cell wall that is synthetized during cell division and elongation. PG forms an extracellular polymer crucial for cellular viability, the synthesis of which is the target of many antibiotics. PG assembly requires a glycosyltransferase (GT) to generate a glycan polymer using a Lipid II substrate, which is then crosslinked to the existing PG via a transpeptidase (TP) reaction. A Shape, Elongation, Division and Sporulation (SEDS) GT enzyme and a Class B Penicillin Binding Protein (PBP) form the core of the multi-protein complex required for PG assembly. Here we used single particle cryo-electron microscopy to determine the structure of a cell elongation-specific E. coli RodA-PBP2 complex. We combine this information with biochemical, genetic, spectroscopic, and computational analyses to identify the Lipid II binding sites and propose a mechanism for Lipid II polymerization. Our data suggest a hypothesis for the movement of the glycan strand from the Lipid II polymerization site of RodA towards the TP site of PBP2, functionally linking these two central enzymatic activities required for cell wall peptidoglycan biosynthesis.
Multiscale dynamics of charging and plating in graphite electrodes coupling operando microscopy and phase-field modelling
Authors: Lu Xuekun , Lagnoni Marco , Bertei Antonio , Das Supratim , Owen Rhodri E. , Li Qi , O’Regan Kieran , Wade Aaron , Finegan Donal P. , Kendrick Emma , Bazant Martin Z. , Brett Dan J. L. , Shearing Paul R.
Published: August 2023

The phase separation dynamics in graphitic anodes significantly affects lithium plating propensity, which is the major degradation mechanism that impairs the safety and fast charge capabilities of automotive lithium-ion batteries. In this study, we present comprehensive investigation employing operando high-resolution optical microscopy combined with non-equilibrium thermodynamics implemented in a multi-dimensional (1D+1D to 3D) phase-field modeling framework to reveal the rate-dependent spatial dynamics of phase separation and plating in graphite electrodes. Here we visualize and provide mechanistic understanding of the multistage phase separation, plating, inter/intra-particle lithium exchange and plated lithium back-intercalation phenomena. A strong dependence of intra-particle lithiation heterogeneity on the particle size, shape, orientation, surface condition and C-rate at the particle level is observed, which leads to early onset of plating spatially resolved by a 3D image-based phase-field model. Moreover, we highlight the distinct relaxation processes at different state-of-charges (SOCs), wherein thermodynamically unstable graphite particles undergo a drastic intra-particle lithium redistribution and inter-particle lithium exchange at intermediate SOCs, whereas the electrode equilibrates much slower at low and high SOCs. These physics-based insights into the distinct SOC-dependent relaxation efficiency provide new perspective towards developing advanced fast charge protocols to suppress plating and shorten the constant voltage regime.
Room temperature energy-efficient spin-orbit torque switching in two-dimensional van der Waals Fe3GeTe2 induced by topological insulators
Authors: Wang Haiyu , Wu Hao , Zhang Jie , Liu Yingjie , Chen Dongdong , Pandey Chandan , Yin Jialiang , Wei Dahai , Lei Na , Shi Shuyuan , Lu Haichang , Li Peng , Fert Albert , Wang Kang L. , Nie Tianxiao , Zhao Weisheng
Published: August 2023

Two-dimensional (2D) ferromagnetic materials with unique magnetic properties have great potential for next-generation spintronic devices with high flexibility, easy controllability, and high heretointegrability. However, realizing magnetic switching with low power consumption at room temperature is challenging. Here, we demonstrate the room-temperature spin-orbit torque (SOT) driven magnetization switching in an all-van der Waals (vdW) heterostructure using an optimized epitaxial growth approach. The topological insulator Bi2Te3 not only raises the Curie temperature of Fe3GeTe2 (FGT) through interfacial exchange coupling but also works as a spin current source allowing the FGT to switch at a low current density of ~2.2×106 A/cm2. The SOT efficiency is ~2.69, measured at room temperature. The temperature and thickness-dependent SOT efficiency prove that the larger SOT in our system mainly originates from the nontrivial topological origin of the heterostructure. Our experiments enable an all-vdW SOT structure and provides a solid foundation for the implementation of room-temperature all-vdW spintronic devices in the future.
Magnetization reversal through an antiferromagnetic state
Authors: Ghara Somnath , Barts Evgenii , Vasin Kirill , Kamenskyi Dmytro , Prodan Lilian , Tsurkan Vladimir , Kézsmárki István , Mostovoy Maxim , Deisenhofer Joachim
Published: August 2023

Magnetization reversal in ferro- and ferrimagnets is a well-known archetype of non-equilibrium processes, where the volume fractions of the oppositely magnetized domains vary and perfectly compensate each other at the coercive magnetic field. Here, we report on a fundamentally new pathway for magnetization reversal that is mediated by an antiferromagnetic state. Consequently, an atomic-scale compensation of the magnetization is realized at the coercive field, instead of the mesoscopic or macroscopic domain cancellation in canonical reversal processes. We demonstrate this unusual magnetization reversal on the Zn-doped polar magnet Fe2Mo3O8. Hidden behind the conventional ferrimagnetic hysteresis loop, the surprising emergence of the antiferromagnetic phase at the coercive fields is disclosed by a sharp peak in the field-dependence of the electric polarization. In addition, at the magnetization reversal our THz spectroscopy studies reveal the reappearance of the magnon mode that is only present in the pristine antiferromagnetic state. According to our microscopic calculations, this unusual process is governed by the dominant intralayer coupling, strong easy-axis anisotropy and spin fluctuations, which result in a complex interplay between the ferrimagnetic and antiferromagnetic phases. Such antiferro-state-mediated reversal processes offer novel concepts for magnetization control, and may also emerge for other ferroic orders.
Structural basis of lipid-droplet localization of 17-beta-hydroxysteroid dehydrogenase 13
Authors: Liu Shenping , Sommese Ruth F. , Nedoma Nicole L. , Stevens Lucy Mae , Dutra Jason K. , Zhang Liying , Edmonds David J. , Wang Yang , Garnsey Michelle , Clasquin Michelle F.
Published: August 2023

Hydroxysteroid 17-beta-dehydrogenase 13 (HSD17B13) is a hepatic lipid droplet-associated enzyme that is upregulated in patients with non-alcoholic fatty liver disease. Recently, there have been several reports that predicted loss of function variants in HSD17B13 protect against the progression of steatosis to non-alcoholic steatohepatitis with fibrosis and hepatocellular carcinoma. Here we report crystal structures of full length HSD17B13 in complex with its NAD+ cofactor, and with lipid/detergent molecules and small molecule inhibitors from two distinct series in the ligand binding pocket. These structures provide insights into a mechanism for lipid droplet-associated proteins anchoring to membranes as well as a basis for HSD17B13 variants disrupting function. Two series of inhibitors interact with the active site residues and the bound cofactor similarly, yet they occupy different paths leading to the active site. These structures provide ideas for structure-based design of inhibitors that may be used in the treatment of liver disease.
Molecular architecture and conservation of an immature human endogenous retrovirus
Authors: Krebs Anna-Sophia , Liu Hsuan-Fu , Zhou Ye , Rey Juan S. , Levintov Lev , Shen Juan , Howe Andrew , Perilla Juan R. , Bartesaghi Alberto , Zhang Peijun
Published: August 2023

The human endogenous retrovirus K (HERV-K) is the most recently acquired endogenous retrovirus in the human genome and is activated and expressed in many cancers and amyotrophic lateral sclerosis. We present the immature HERV-K capsid structure at 3.2 Å resolution determined from native virus-like particles using cryo-electron tomography and subtomogram averaging. The structure shows a hexamer unit oligomerized through a 6-helix bundle, which is stabilized by a small molecule analogous to IP6 in immature HIV-1 capsid. The HERV-K immature lattice is assembled via highly conserved dimer and trimer interfaces, as detailed through all-atom molecular dynamics simulations and supported by mutational studies. A large conformational change mediated by the linker between the N-terminal and the C-terminal domains of CA occurs during HERV-K maturation. Comparison between HERV-K and other retroviral immature capsid structures reveals a highly conserved mechanism for the assembly and maturation of retroviruses across genera and evolutionary time.
Interplay of structural chirality, electron spin and topological orbital in chiral molecular spin valves
Authors: Adhikari Yuwaraj , Liu Tianhan , Wang Hailong , Hua Zhenqi , Liu Haoyang , Lochner Eric , Schlottmann Pedro , Yan Binghai , Zhao Jianhua , Xiong Peng
Published: August 2023

Chirality has been a property of central importance in physics, chemistry and biology for more than a century. Recently, electrons were found to become spin polarized after transmitting through chiral molecules, crystals, and their hybrids. This phenomenon, called chirality-induced spin selectivity (CISS), presents broad application potentials and far-reaching fundamental implications involving intricate interplays among structural chirality, topological states, and electronic spin and orbitals. However, the microscopic picture of how chiral geometry influences electronic spin remains elusive, given the negligible spin-orbit coupling (SOC) in organic molecules. In this work, we address this issue via a direct comparison of magnetoconductance (MC) measurements on magnetic semiconductor-based chiral molecular spin valves with normal metal electrodes of contrasting SOC strengths. The experiment reveals that a heavy-metal electrode provides SOC to convert the orbital polarization induced by the chiral molecular structure to spin polarization. Our results illustrate the essential role of SOC in the metal electrode for the CISS spin valve effect. A tunneling model with a magnetochiral modulation of the potential barrier is shown to quantitatively account for the unusual transport behavior.
Outer membrane vesicles from a mosquito commensal mediate targeted killing of Plasmodium parasites via the phosphatidylcholine scavenging pathway
Authors: Gao Han , Jiang Yongmao , Wang Lihua , Wang Guandong , Hu Wenqian , Dong Ling , Wang Sibao
Published: August 2023

The gut microbiota is a crucial modulator of Plasmodium infection in mosquitoes, including the production of anti-Plasmodium effector proteins. But how the commensal-derived effectors are translocated into Plasmodium parasites remains obscure. Here we show that a natural Plasmodium blocking symbiotic bacterium Serratia ureilytica Su_YN1 delivers the effector lipase AmLip to Plasmodium parasites via outer membrane vesicles (OMVs). After a blood meal, host serum strongly induces Su_YN1 to release OMVs and the antimalarial effector protein AmLip into the mosquito gut. AmLip is first secreted into the extracellular space via the T1SS and then preferentially loaded on the OMVs that selectively target the malaria parasite, leading to targeted killing of the parasites. Notably, these serum-induced OMVs incorporate certain serum-derived lipids, such as phosphatidylcholine, which is critical for OMV uptake by Plasmodium via the phosphatidylcholine scavenging pathway. These findings reveal that this gut symbiotic bacterium evolved to deliver secreted effector molecules in the form of extracellular vesicles to selectively attack parasites and render mosquitoes refractory to Plasmodium infection. The discovery of the role of gut commensal-derived OMVs as carriers in cross-kingdom communication between mosquito microbiota and Plasmodium parasites offers a potential innovative strategy for blocking malaria transmission.
Severe COVID-19 patients exhibit elevated levels of autoantibodies targeting cardiolipin and platelet glycoprotein with age: a systems biology approach
Authors: Fonseca Dennyson Leandro M. , Filgueiras Igor Salerno , Marques Alexandre H. C. , Vojdani Elroy , Halpert Gilad , Ostrinski Yuri , Baiocchi Gabriela Crispim , Plaça Desirée Rodrigues , Freire Paula P. , Pour Shahab Zaki , Moll Guido , Catar Rusan , Lavi Yael Bublil , Silverberg Jonathan I. , Zimmerman Jason , Cabral-Miranda Gustavo , Carvalho Robson F. , Khan Taj Ali , Heidecke Harald , Dalmolin Rodrigo J. S. , Luchessi Andre Ducati , Ochs Hans D. , Schimke Lena F. , Amital Howard , Riemekasten Gabriela , Zyskind Israel , Rosenberg Avi Z. , Vojdani Aristo , Shoenfeld Yehuda , Cabral-Marques Otavio
Published: August 2023

Age is a significant risk factor for the coronavirus disease 2019 (COVID-19) severity due to immunosenescence and certain age-dependent medical conditions (e.g., obesity, cardiovascular disorder, and chronic respiratory disease). However, despite the well-known influence of age on autoantibody biology in health and disease, its impact on the risk of developing severe COVID-19 remains poorly explored. Here, we performed a cross-sectional study of autoantibodies directed against 58 targets associated with autoimmune diseases in 159 individuals with different COVID-19 severity (71 mild, 61 moderate, and 27 with severe symptoms) and 73 healthy controls. We found that the natural production of autoantibodies increases with age and is exacerbated by SARS-CoV-2 infection, mostly in severe COVID-19 patients. Multiple linear regression analysis showed that severe COVID-19 patients have a significant age-associated increase of autoantibody levels against 16 targets (e.g., amyloid β peptide, β catenin, cardiolipin, claudin, enteric nerve, fibulin, insulin receptor a, and platelet glycoprotein). Principal component analysis with spectrum decomposition and hierarchical clustering analysis based on these autoantibodies indicated an age-dependent stratification of severe COVID-19 patients. Random forest analysis ranked autoantibodies targeting cardiolipin, claudin, and platelet glycoprotein as the three most crucial autoantibodies for the stratification of severe COVID-19 patients ≥50 years of age. Follow-up analysis using binomial logistic regression found that anti-cardiolipin and anti-platelet glycoprotein autoantibodies significantly increased the likelihood of developing a severe COVID-19 phenotype with aging. These findings provide key insights to explain why aging increases the chance of developing more severe COVID-19 phenotypes.
Plant and microbial science and technology as cornerstones to Bioregenerative Life Support Systems in space
Authors: De Micco Veronica , Amitrano Chiara , Mastroleo Felice , Aronne Giovanna , Battistelli Alberto , Carnero-Diaz Eugenie , De Pascale Stefania , Detrell Gisela , Dussap Claude-Gilles , Ganigué Ramon , Jakobsen Øyvind Mejdell , Poulet Lucie , Van Houdt Rob , Verseux Cyprien , Vlaeminck Siegfried E. , Willaert Ronnie , Leys Natalie
Published: August 2023

Long-term human space exploration missions require environmental control and closed Life Support Systems (LSS) capable of producing and recycling resources, thus fulfilling all the essential metabolic needs for human survival in harsh space environments, both during travel and on orbital/planetary stations. This will become increasingly necessary as missions reach farther away from Earth, thereby limiting the technical and economic feasibility of resupplying resources from Earth. Further incorporation of biological elements into state-of-the-art (mostly abiotic) LSS, leading to bioregenerative LSS (BLSS), is needed for additional resource recovery, food production, and waste treatment solutions, and to enable more self-sustainable missions to the Moon and Mars. There is a whole suite of functions crucial to sustain human presence in Low Earth Orbit (LEO) and successful settlement on Moon or Mars such as environmental control, air regeneration, waste management, water supply, food production, cabin/habitat pressurization, radiation protection, energy supply, and means for transportation, communication, and recreation. In this paper, we focus on air, water and food production, and waste management, and address some aspects of radiation protection and recreation. We briefly discuss existing knowledge, highlight open gaps, and propose possible future experiments in the short-, medium-, and long-term to achieve the targets of crewed space exploration also leading to possible benefits on Earth.
Deep formation of Earth’s earliest continental crust consistent with subduction
Authors: Hastie Alan R. , Law Sally , Bromiley Geoffrey D. , Fitton J. Godfrey , Harley Simon L. , Muir Duncan D.
Published: August 2023

About four billion years ago, Earth’s outer layer is thought to have been composed mostly of a 25- to 50-km-thick basaltic crust that differentiated to form the oldest stable continental crust. However, the tectonic processes responsible for the formation of this continental material remain controversial. Suggested explanations include convergent plate boundary processes akin to subduction operating today and a variety of relatively shallow (<50 km) non-plate-tectonic intracrustal mechanisms. Here we perform high-pressure–temperature melting experiments on an oceanic plateau analogue for the early basaltic crust and show that magmas with the composition of the early continental crust cannot form at pressures <1.4 GPa (~50 km depth). This suggests that Eoarchaean continental magmas are formed in deep (>50 km) subduction-like environments. Our results support previous Eoarchaean field evidence and analyses of igneous rocks that date to 4.0–3.6 billion years ago, which are consistent with subduction-like processes and suggest a primitive type of plate tectonics operated as long as 4 billion years ago on early Earth.
Therapeutically useful mycobacteriophages BPs and Muddy require trehalose polyphleates
Authors: Wetzel Katherine S. , Illouz Morgane , Abad Lawrence , Aull Haley G. , Russell Daniel A. , Garlena Rebecca A. , Cristinziano Madison , Malmsheimer Silke , Chalut Christian , Hatfull Graham F. , Kremer Laurent
Published: August 2023

Mycobacteriophages show promise as therapeutic agents for non-tuberculous mycobacterium infections. However, little is known about phage recognition of Mycobacterium cell surfaces or mechanisms of phage resistance. We show here that trehalose polyphleates (TPPs)—high-molecular-weight, surface-exposed glycolipids found in some mycobacterial species—are required for infection of Mycobacterium abscessus and Mycobacterium smegmatis by clinically useful phages BPs and Muddy. TPP loss leads to defects in adsorption and infection and confers resistance. Transposon mutagenesis shows that TPP disruption is the primary mechanism for phage resistance. Spontaneous phage resistance occurs through TPP loss by mutation, and some M. abscessus clinical isolates are naturally phage-insensitive due to TPP synthesis gene mutations. Both BPs and Muddy become TPP-independent through single amino acid substitutions in their tail spike proteins, and M. abscessus mutants resistant to TPP-independent phages reveal additional resistance mechanisms. Clinical use of BPs and Muddy TPP-independent mutants should preempt phage resistance caused by TPP loss.
A Multi-Stain Breast Cancer Histological Whole-Slide-Image Data Set from Routine Diagnostics
Authors: Weitz Philippe , Valkonen Masi , Solorzano Leslie , Carr Circe , Kartasalo Kimmo , Boissin Constance , Koivukoski Sonja , Kuusela Aino , Rasic Dusan , Feng Yanbo , Sinius Pouplier Sandra , Sharma Abhinav , Ledesma Eriksson Kajsa , Latonen Leena , Laenkholm Anne-Vibeke , Hartman Johan , Ruusuvuori Pekka , Rantalainen Mattias
Published: August 2023

The analysis of FFPE tissue sections stained with haematoxylin and eosin (H&E) or immunohistochemistry (IHC) is essential for the pathologic assessment of surgically resected breast cancer specimens. IHC staining has been broadly adopted into diagnostic guidelines and routine workflows to assess the status of several established biomarkers, including ER, PGR, HER2 and KI67. Biomarker assessment can also be facilitated by computational pathology image analysis methods, which have made numerous substantial advances recently, often based on publicly available whole slide image (WSI) data sets. However, the field is still considerably limited by the sparsity of public data sets. In particular, there are no large, high quality publicly available data sets with WSIs of matching IHC and H&E-stained tissue sections from the same tumour. Here, we publish the currently largest publicly available data set of WSIs of tissue sections from surgical resection specimens from female primary breast cancer patients with matched WSIs of corresponding H&E and IHC-stained tissue, consisting of 4,212 WSIs from 1,153 patients.
Iridocorneal angle imaging of a human donor eye by spectral-domain optical coherence tomography
Authors: Luo Shangbang , Holland Guy , Khazaeinezhad Reza , Bradford Samantha , Joshi Rohan , Juhasz Tibor
Published: August 2023

Iridocorneal angle (ICA) details particularly the trabecular meshwork (TM), Schlemm’s canal (SC), and collector channels (CCs) play crucial roles in the regulation of the aqueous outflow in the eyes and are closely associated with glaucoma. Current clinical gonioscopy imaging provides no depth information, and studies of 3D high-resolution optical coherence tomography (OCT) imaging of these structures are limited. We developed a custom-built spectral-domain (SD-) OCT imaging system to fully characterize the angle details. Imaging of a human cadaver eye reveals the visibility of details in the TM/SC/CC region via a ’crossline’ scanning and a series of image processing. This shows that ICA imaging can be used for preoperative glaucoma inspections in the clinical setting with the proposed prototype.
Perception, performance, and detectability of conversational artificial intelligence across 32 university courses
Authors: Ibrahim Hazem , Liu Fengyuan , Asim Rohail , Battu Balaraju , Benabderrahmane Sidahmed , Alhafni Bashar , Adnan Wifag , Alhanai Tuka , AlShebli Bedoor , Baghdadi Riyadh , Bélanger Jocelyn J. , Beretta Elena , Celik Kemal , Chaqfeh Moumena , Daqaq Mohammed F. , Bernoussi Zaynab El , Fougnie Daryl , Garcia de Soto Borja , Gandolfi Alberto , Gyorgy Andras , Habash Nizar , Harris J. Andrew , Kaufman Aaron , Kirousis Lefteris , Kocak Korhan , Lee Kangsan , Lee Seungah S. , Malik Samreen , Maniatakos Michail , Melcher David , Mourad Azzam , Park Minsu , Rasras Mahmoud , Reuben Alicja , Zantout Dania , Gleason Nancy W. , Makovi Kinga , Rahwan Talal , Zaki Yasir
Published: August 2023

The emergence of large language models has led to the development of powerful tools such as ChatGPT that can produce text indistinguishable from human-generated work. With the increasing accessibility of such technology, students across the globe may utilize it to help with their school work—a possibility that has sparked ample discussion on the integrity of student evaluation processes in the age of artificial intelligence (AI). To date, it is unclear how such tools perform compared to students on university-level courses across various disciplines. Further, students’ perspectives regarding the use of such tools in school work, and educators’ perspectives on treating their use as plagiarism, remain unknown. Here, we compare the performance of the state-of-the-art tool, ChatGPT, against that of students on 32 university-level courses. We also assess the degree to which its use can be detected by two classifiers designed specifically for this purpose. Additionally, we conduct a global survey across five countries, as well as a more in-depth survey at the authors’ institution, to discern students’ and educators’ perceptions of ChatGPT’s use in school work. We find that ChatGPT’s performance is comparable, if not superior, to that of students in a multitude of courses. Moreover, current AI-text classifiers cannot reliably detect ChatGPT’s use in school work, due to both their propensity to classify human-written answers as AI-generated, as well as the relative ease with which AI-generated text can be edited to evade detection. Finally, there seems to be an emerging consensus among students to use the tool, and among educators to treat its use as plagiarism. Our findings offer insights that could guide policy discussions addressing the integration of artificial intelligence into educational frameworks.
Preparation of fast-swelling porous superabsorbent hydrogels with high saline water absorbency under pressure by foaming and post surface crosslinking
Authors: Zhai Naihua , Wang Baogui
Published: August 2023

Superabsorbent hydrogels have wide applications in many fields because of their unique water absorbing performance. In spite of decades of research about superabsorbent hydrogels, high water absorbency under pressure and fast-swelling are still challenging and highly desired for their applications in hygienic products and others. Here, we report preparation of fast-swelling porous starch-g-poly(acrylic acid)/poly(vinyl alcohol) superabsorbent hydrogels with high saline water absorbency under pressure by foaming and post surface crosslinking. 2,2′-Azobis(2-amidinopropane) dihydrochloride (AIBA) was used as a new porogen instead of conventional porogens like NaHCO3. Post surface crosslinking of the hydrogel was achieved using glycerol via the esterification reaction. AIBA is a better porogen than NaHCO3 regarding porosity and swelling performance of the hydrogels, and its content has great influences on structure and swelling performance of the hydrogels including water absorbency and swelling rate. Also, the surface crosslinking using glycerol can significantly enhance the saline water absorbency under pressure (2 kPa) but at the sacrifice of the swelling rate. Consequently, the hydrogels show high water absorbencies for deionized water (560 g/g), 0.9 wt% NaCl solution (58 g/g), 0.9 wt% NaCl solution under 2 kPa pressure (28 g/g) and fast-swelling (31 s to achieve a highly swelling state).
Lifelong effects of prenatal and early postnatal stress on the hippocampus, amygdala, and psychological states of Holocaust survivors
Authors: Fňašková Monika , Říha Pavel , Nečasová Markéta , Preiss Marek , Rektor Ivan
Published: August 2023

This study focuses on hippocampal and amygdala volume, seed-based connectivity, and psychological traits of Holocaust survivors who experienced stress during prenatal and early postnatal development. We investigated people who lived in Central Europe during the Holocaust and who, as Jews, were in imminent danger. The group who experienced stress during their prenatal development and early postnatal (PreP) period (n = 11) were compared with a group who experienced Holocaust-related stress later in their lives: in late childhood, adolescence, and early adulthood (ChA) (n = 21). The results of volumetry analysis showed significantly lower volumes of both hippocampi and the right amygdala in the PreP group. Seed-based connectivity analysis revealed increased connectivity from the seed in the right amygdala to the middle and posterior cingulate cortex, caudate, and inferior left frontal operculum in the PreP group. Psychological testing found higher levels of traumatic stress symptoms (TCS-40) and lower levels of well-being (SOS-10) in the PreP group than in the ChA group. The results of our study demonstrate that extreme stress experienced during prenatal and early postnatal life has a profound lifelong impact on the hippocampus and amygdala and on several psychological characteristics.
A randomized trial on differential changes in thought and affect after mindfulness versus dyadic practice indicates phenomenological fingerprints of app-based interventions
Authors: Petzold Paul , Silveira Sarita , Godara Malvika , Matthaeus Hannah , Singer Tania
Published: August 2023

Contemplative practice has demonstrated benefits for mental health and well-being. Most previous studies, however, implemented in-person trainings containing a mix of different, mostly solitary, practices and focused on pre- to post-training outcomes. In this randomized trial, we explore the immediate differential efficacy of two daily app-delivered practices in shifting emotional (valence, arousal) and thinking patterns (thought content on future-past, self-other, positive–negative dimensions). For 10 weeks of daily training, 212 participants (18–65 years) performed either a novel 12-min partner-based socio-emotional practice (Affect Dyad) or a 12-min attention-focused solitary mindfulness-based practice. Using ordinal Bayesian multilevel modeling, we found that both practice types led to more positive affect and higher arousal. However, whereas mindfulness-based practice partly led to a decrease in active thoughts, particularly in future-, other-related and negative thoughts, the Dyad in contrast led to increases in other-related, and positive thoughts. This shift towards more social and positive thoughts may specifically support overcoming ruminative thinking patterns associated with self-related and negative thought content. Overall, these differential findings may help inform the adaptation of scalable app-based mental trainings in different segments of the population with the goal to improve mental health and well-being.
Formalizing psychological interventions through network control theory
Authors: Stocker Julia Elina , Koppe Georgia , Reich Hanna , Heshmati Saeideh , Kittel-Schneider Sarah , Hofmann Stefan G. , Hahn Tim , van der Maas Han L. J. , Waldorp Lourens , Jamalabadi Hamidreza
Published: August 2023

Despite the growing deployment of network representation to comprehend psychological phenomena, the question of whether and how networks can effectively describe the effects of psychological interventions remains elusive. Network control theory, the engineering study of networked interventions, has recently emerged as a viable methodology to characterize and guide interventions. However, there is a scarcity of empirical studies testing the extent to which it can be useful within a psychological context. In this paper, we investigate a representative psychological intervention experiment, use network control theory to model the intervention and predict its effect. Using this data, we showed that: (1) the observed psychological effect, in terms of sensitivity and specificity, relates to the regional network control theoretic metrics (average and modal controllability), (2) the size of change following intervention negatively correlates with a whole-network topology that quantifies the “ease” of change as described by control theory (control energy), and (3) responses after intervention can be predicted based on formal results from control theory. These insights assert that network control theory has significant potential as a tool for investigating psychological interventions. Drawing on this specific example and the overarching framework of network control theory, we further elaborate on the conceptualization of psychological interventions, methodological considerations, and future directions in this burgeoning field.
Biological activities and biosorption potential of red algae (Corallina officinalis) to remove toxic malachite green dye
Authors: Youssef Elen Emad , Beshay Botros Y. , Tonbol Kareem , Makled Sarah O.
Published: August 2023

This research aims to use eco-friendly Corallina officinalis as an adsorbent for removing harmful malachite green dye streams from industrial effluent, promoting sustainable living and effective microbial growth inhibition. Corallina officinalis biomass was tested for textile dye biosorption, as well as its antibacterial, antioxidant, and cytotoxic properties. The effects of certain parameters, involving pH solution, initial dye concentration, algae dose, and contact time, were investigated on the sorption of dye. Fourier transform infrared spectroscopy and scanning electron microscopy were also used and, the results showed that the functional groups on the surface of algae played an important part in the biosorption process. It was noted that the kinetic data were significantly prominent by the Pseudo-second-order model with regression correlation coefficient $${r}_{2}^{2}$$

r

2

2

values with an average of 0.95232. The biosorption was compatible with both the Freundlich (R2 = 0.9843), and Langmuir (R2 = 0.9653) isotherms, and the maximum removal efficiency for dye reached up to 99.9% in 2 h, 27 °C, stirring speed 120 rpm, pH 6, initial dye concentration 20 mg L−1, and biomass dose 0.03 g L−1. Corallina officinalis had higher antimicrobial activity, with values of minimum inhibitory concentrations ranging from 0.156 to 5 mg mL−1. Corallina officinalis exerted significant radical scavenging activity against tested free radicals. The extract was examined for cytotoxic activity using nine cancer cell lines, which exhibited high cytotoxicity for colon adenocarcinoma with an IC50 value of 25.895 µg mL−1.
Veterinary education and experience shape beliefs about dog breeds Part 1: Pain sensitivity
Authors: Caddiell Rachel M. P. , White Philip , Lascelles B. Duncan X. , Royal Kenneth , Ange-van Heugten Kimberly , Gruen Margaret E.
Published: August 2023

Over 95% of veterinarians report believing that dog breeds differ in pain sensitivity. Ratings made by veterinarians differ from those of the general public, suggesting these beliefs may be learned during veterinary training or clinical experiences. Therefore, the current study’s primary objective was to evaluate dog breed pain sensitivity ratings during veterinary training and compare these ratings to those of the general public and undergraduates in animal-health related fields. Using an online survey, members of the general public, undergraduates, veterinary students across all four years, and veterinary faculty and staff rated pain sensitivity of 10 different dog breeds, identified only by their pictures. Compared to the general public and undergraduates, veterinary students rated pain sensitivity across breeds of dog more similarly to veterinary faculty and staff. Further, when undergraduates had clinical experience, they also rated certain dog breeds in a similar way to the veterinary students and professionals. Our findings suggest that veterinary education and clinical experiences influence pain sensitivity ratings across dog breeds. Future research should identify how these pain sensitivity beliefs are communicated and whether these beliefs affect recognition and treatment of pain by veterinarians.
Transport pathways and kinetics of cerebrospinal fluid tracers in mouse brain observed by dynamic contrast-enhanced MRI
Authors: Zhu Yuran , Wang Guanhua , Kolluru Chaitanya , Gu Yuning , Gao Huiyun , Zhang Jing , Wang Yunmei , Wilson David L. , Zhu Xiaofeng , Flask Chris A. , Yu Xin
Published: August 2023

Recent studies have suggested the glymphatic system as a key mechanism of waste removal in the brain. Dynamic contrast-enhanced MRI (DCE-MRI) using intracisternally administered contrast agents is a promising tool for assessing glymphatic function in the whole brain. In this study, we evaluated the transport kinetics and distribution of three MRI contrast agents with vastly different molecular sizes in mice. Our results demonstrate that oxygen-17 enriched water (H217O), which has direct access to parenchymal tissues via aquaporin-4 water channels, exhibited significantly faster and more extensive transport compared to the two gadolinium-based contrast agents (Gd-DTPA and GadoSpin). Time-lagged correlation and clustering analyses also revealed different transport pathways for Gd-DTPA and H217O. Furthermore, there were significant differences in transport kinetics of the three contrast agents to the lateral ventricles, reflecting the differences in forces that drive solute transport in the brain. These findings suggest the size-dependent transport pathways and kinetics of intracisternally administered contrast agents and the potential of DCE-MRI for assessing multiple aspects of solute transport in the glymphatic system.