bluuebunny/crossref_metadata_2025 huggingface dataset:
A 3D printable tissue adhesive
Authors: Wu Sarah J. , Wu Jingjing , Kaser Samuel J. , Roh Heejung , Shiferaw Ruth D. , Yuk Hyunwoo , Zhao Xuanhe
Published: February 2024

Tissue adhesives are promising alternatives to sutures and staples for joining tissues, sealing defects, and immobilizing devices. However, existing adhesives mostly take the forms of glues or hydrogels, which offer limited versatility. We report a direct-ink-write 3D printable tissue adhesive which can be used to fabricate bioadhesive patches and devices with programmable architectures, unlocking new potential for application-specific designs. The adhesive is conformable and stretchable, achieves robust adhesion with wet tissues within seconds, and exhibits favorable biocompatibility. In vivo rat trachea and colon defect models demonstrate the fluid-tight tissue sealing capability of the printed patches, which maintained adhesion over 4 weeks. Moreover, incorporation of a blood-repelling hydrophobic matrix enables the printed patches to seal actively bleeding tissues. Beyond wound closure, the 3D printable adhesive has broad applicability across various tissue-interfacing devices, highlighted through representative proof-of-concept designs. Together, this platform offers a promising strategy toward developing advanced tissue adhesive technologies.
Endogenous cannabinoids in the piriform cortex tune olfactory perception
Authors: Terral Geoffrey , Harrell Evan , Lepousez Gabriel , Wards Yohan , Huang Dinghuang , Dolique Tiphaine , Casali Giulio , Nissant Antoine , Lledo Pierre-Marie , Ferreira Guillaume , Marsicano Giovanni , Roux Lisa
Published: February 2024

Sensory perception depends on interactions between external inputs transduced by peripheral sensory organs and internal network dynamics generated by central neuronal circuits. In the sensory cortex, desynchronized network states associate with high signal-to-noise ratio stimulus-evoked responses and heightened perception. Cannabinoid-type-1-receptors (CB1Rs) - which influence network coordination in the hippocampus - are present in anterior piriform cortex (aPC), a sensory paleocortex supporting olfactory perception. Yet, how CB1Rs shape aPC network activity and affect odor perception is unknown. Using pharmacological manipulations coupled with multi-electrode recordings or fiber photometry in the aPC of freely moving male mice, we show that systemic CB1R blockade as well as local drug infusion increases the amplitude of gamma oscillations in aPC, while simultaneously reducing the occurrence of synchronized population events involving aPC excitatory neurons. In animals exposed to odor sources, blockade of CB1Rs reduces correlation among aPC excitatory units and lowers behavioral olfactory detection thresholds. These results suggest that endogenous endocannabinoid signaling promotes synchronized population events and dampen gamma oscillations in the aPC which results in a reduced sensitivity to external sensory inputs.
Comparative effectiveness of alternative intervals between first and second doses of the mRNA COVID-19 vaccines
Authors: Shioda Kayoko , Breskin Alexander , Harati Pravara , Chamberlain Allison T. , Komura Toshiaki , Lopman Benjamin A. , Rogawski McQuade Elizabeth T.
Published: February 2024

The optimal interval between the first and second doses of COVID-19 mRNA vaccines has not been thoroughly evaluated. Employing a target trial emulation approach, we compared the effectiveness of different interdose intervals among >6 million mRNA vaccine recipients in Georgia, USA, from December 2020 to March 2022. We compared three protocols defined by interdose interval: recommended by the Food and Drug Administration (FDA) (17-25 days for Pfizer-BioNTech; 24-32 days for Moderna), late-but-allowable (26-42 days for Pfizer-BioNTech; 33-49 days for Moderna), and late ( ≥ 43 days for Pfizer-BioNTech; ≥50 days for Moderna). In the short-term, the risk of SARS-CoV-2 infection was lowest under the FDA-recommended protocol. Longer-term, the late-but-allowable protocol resulted in the lowest risk (risk ratio on Day 120 after the first dose administration compared to the FDA-recommended protocol: 0.83 [95% confidence interval: 0.82-0.84]). Here, we showed that delaying the second dose by 1-2 weeks may provide stronger long-term protection.
Children born after assisted reproduction more commonly carry a mitochondrial genotype associating with low birthweight
Authors: Mertens Joke , Belva Florence , van Montfoort Aafke P. A. , Regin Marius , Zambelli Filippo , Seneca Sara , Couvreu de Deckersberg Edouard , Bonduelle Maryse , Tournaye Herman , Stouffs Katrien , Barbé Kurt , Smeets Hubert J. M. , Van de Velde Hilde , Sermon Karen , Blockeel Christophe , Spits Claudia
Published: February 2024

Children conceived through assisted reproductive technologies (ART) have an elevated risk of lower birthweight, yet the underlying cause remains unclear. Our study explores mitochondrial DNA (mtDNA) variants as contributors to birthweight differences by impacting mitochondrial function during prenatal development. We deep-sequenced the mtDNA of 451 ART and spontaneously conceived (SC) individuals, 157 mother-child pairs and 113 individual oocytes from either natural menstrual cycles or after ovarian stimulation (OS) and find that ART individuals carried a different mtDNA genotype than SC individuals, with more de novo non-synonymous variants. These variants, along with rRNA variants, correlate with lower birthweight percentiles, independent of conception mode. Their higher occurrence in ART individuals stems from de novo mutagenesis associated with maternal aging and OS-induced oocyte cohort size. Future research will establish the long-term health consequences of these changes and how these findings will impact the clinical practice and patient counselling in the future.
Androgen deprivation induces double-null prostate cancer via aberrant nuclear export and ribosomal biogenesis through HGF and Wnt activation
Authors: Kim Won Kyung , Buckley Alyssa J. , Lee Dong-Hoon , Hiroto Alex , Nenninger Christian H. , Olson Adam W. , Wang Jinhui , Li Zhuo , Vikram Rajeev , Adzavon Yao Mawulikplimi , Yau Tak-yu , Bao Yigang , Kahn Michael , Geradts Joseph , Xiao Guang-Qian , Sun Zijie
Published: February 2024

Androgen deprivation therapy (ADT) targeting androgen/androgen receptor (AR)- signaling pathways is the main therapy for advanced prostate cancer (PCa). However, ADT eventually fails in most patients who consequently develop castration-resistant prostate cancer (CRPC). While more potent AR antagonists and blockers for androgen synthesis were developed to improve clinical outcomes, they also show to induce more diverse CRPC phenotypes. Specifically, the AR- and neuroendocrine-null PCa, DNPC, occurs in abiraterone and enzalutamide-treated patients. Here, we uncover that current ADT induces aberrant HGF/MET signaling activation that further elevates Wnt/β-catenin signaling in human DNPC samples. Co-activation of HGF/MET and Wnt/β-catenin axes in mouse prostates induces DNPC-like lesions. Single-cell RNA sequencing analyses identify increased expression and activity of XPO1 and ribosomal proteins in mouse DNPC-like cells. Elevated expression of XPO1 and ribosomal proteins is also identified in clinical DNPC specimens. Inhibition of XPO1 and ribosomal pathways represses DNPC growth in both in vivo and ex vivo conditions, evidencing future therapeutic targets.
Symmetrically pulsating bubbles swim in an anisotropic fluid by nematodynamics
Authors: Kim Sung-Jo , Kos Žiga , Um Eujin , Jeong Joonwoo
Published: February 2024

Swimming in low-Reynolds-number fluids requires the breaking of time-reversal symmetry and centrosymmetry. Microswimmers, often with asymmetric shapes, exhibit nonreciprocal motions or exploit nonequilibrium processes to propel. The role of the surrounding fluid has also attracted attention because viscoelastic, non-Newtonian, and anisotropic properties of fluids matter in propulsion efficiency and navigation. Here, we experimentally demonstrate that anisotropic fluids, nematic liquid crystals (NLC), can make a pulsating spherical bubble swim despite its centrosymmetric shape and time-symmetric motion. The NLC breaks the centrosymmetry by a deformed nematic director field with a topological defect accompanying the bubble. The nematodynamics renders the nonreciprocity in the pulsation-induced fluid flow. We also report speed enhancement by confinement and the propulsion of another symmetry-broken bubble dressed by a bent disclination. Our experiments and theory propose another possible mechanism of moving bodies in complex fluids by spatiotemporal symmetry breaking.
Globally representative evidence on the actual and perceived support for climate action
Authors: Andre Peter , Boneva Teodora , Chopra Felix , Falk Armin
Published: February 2024

Mitigating climate change necessitates global cooperation, yet global data on individuals’ willingness to act remain scarce. In this study, we conducted a representative survey across 125 countries, interviewing nearly 130,000 individuals. Our findings reveal widespread support for climate action. Notably, 69% of the global population expresses a willingness to contribute 1% of their personal income, 86% endorse pro-climate social norms and 89% demand intensified political action. Countries facing heightened vulnerability to climate change show a particularly high willingness to contribute. Despite these encouraging statistics, we document that the world is in a state of pluralistic ignorance, wherein individuals around the globe systematically underestimate the willingness of their fellow citizens to act. This perception gap, combined with individuals showing conditionally cooperative behaviour, poses challenges to further climate action. Therefore, raising awareness about the broad global support for climate action becomes critically important in promoting a unified response to climate change.
The Cabrières Biota (France) provides insights into Ordovician polar ecosystems
Authors: Saleh Farid , Lustri Lorenzo , Gueriau Pierre , Potin Gaëtan J.-M. , Pérez-Peris Francesc , Laibl Lukáš , Jamart Valentin , Vite Antoine , Antcliffe Jonathan B. , Daley Allison C. , Nohejlová Martina , Dupichaud Christophe , Schöder Sebastian , Bérard Emilie , Lynch Sinéad , Drage Harriet B. , Vaucher Romain , Vidal Muriel , Monceret Eric , Monceret Sylvie , Lefebvre Bertrand
Published: February 2024

Early Palaeozoic sites with soft-tissue preservation are predominantly found in Cambrian rocks and tend to capture past tropical and temperate ecosystems. In this study, we describe the diversity and preservation of the Cabrières Biota, a newly discovered Early Ordovician Lagerstätte from Montagne Noire, southern France. The Cabrières Biota showcases a diverse polar assemblage of both biomineralized and soft-bodied organisms predominantly preserved in iron oxides. Echinoderms are extremely scarce, while sponges and algae are abundantly represented. Non-biomineralized arthropod fragments are also preserved, along with faunal elements reminiscent of Cambrian Burgess Shale-type ecosystems, such as armoured lobopodians. The taxonomic diversity observed in the Cabrières Biota mixes Early Ordovician Lagerstätten taxa with Cambrian forms. By potentially being the closest Lagerstätte to the South Pole, the Cabrières Biota probably served as a biotic refuge amid the high-water temperatures of the Early Ordovician, and shows comparable ecological structuring to modern polar communities.
Synthesis of lipid-linked precursors of the bacterial cell wall is governed by a feedback control mechanism in Pseudomonas aeruginosa
Authors: Marmont Lindsey S. , Orta Anna K. , Baileeves Becca W. A. , Sychantha David , Fernández-Galliano Ana , Li Yancheng E. , Greene Neil G. , Corey Robin A. , Stansfeld Phillip J. , Clemons William M. , Bernhardt Thomas G.
Published: February 2024

Many bacterial surface glycans such as the peptidoglycan (PG) cell wall are built from monomeric units linked to a polyprenyl lipid carrier. How this limiting carrier is distributed among competing pathways has remained unclear. Here we describe the isolation of hyperactive variants of Pseudomonas aeruginosa MraY, the enzyme that forms the first lipid-linked PG precursor. These variants result in the elevated production of the final PG precursor lipid II in cells and are hyperactive in vitro. The activated MraY variants have substitutions that map to a cavity on the extracellular side of the dimer interface, far from the active site. Our structural and molecular dynamics results suggest that this cavity is a binding site for externalized lipid II. Overall, our results support a model in which excess externalized lipid II allosterically inhibits MraY, providing a feedback mechanism that prevents the sequestration of lipid carrier in the PG biogenesis pathway.
Fabrication and characterization of electrically conducting electrochemically synthesized polypyrrole-based enzymatic biofuel cell anode with biocompatible redox mediator vitamin K3
Authors: Khan Maha , Inamuddin
Published: February 2024

Enzymatic biofuel cells (EBFCs) hold tremendous potential to power biomedical devices, biosensors, and bioelectronics. Unlike conventional toxic batteries, these electrochemical devices are biocompatible, harnessing energy from physiological fluids and producing usable electrical energy. But the commercialization of EBFCs is limited by the low operational stability, limited power output and poor electron transport efficiency of the enzymatic electrodes. In this study, a novel bioanode exhibiting a high electron transfer ability and long-term stability was fabricated. For the preparation of the anode, surfactant-assisted polypyrrole (PPy) was electrochemically co-deposited on a platinum wire with the simultaneous entrapment of vitamin K3 (VK3) and GOx (glucose oxidase) in the PPy matrix. Herein, conducting PPy acts as an electron transfer enhancer and provides appropriate electrical communication between the active site of the enzyme glucose oxidase (GOx) and the electrode surface. Biocompatible redox mediator vitamin K3 was employed as an electron transfer mediator to shuttle electrons between the oxidized fuel glucose and surface of the electrode in the electrochemical cell. The electrical conductivity of PPy was measured using the four-probe technique of conductivity measurement of semiconductors. The morphological characterization of as-synthesized anode (PPy/CTAB/VK3/GOx) was performed by Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), X-ray diffraction (XRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The electrochemical characterization was studied by cyclic voltammetry (CV), linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS) techniques. It was observed that the room-temperature conductivity of PPy lies in the semiconducting range and it also shows good stability on exposure to laboratory air, making it a promising material to provide electrical contact. The study developed a bioanode producing a modest current density of 6.35 mA cm–2 in 20 mM glucose solution. The stability, current output and ease of manufacturing process of the electrode make it particularly suitable for employment in biofuel cell applications.
Label-free visualization and quantification of the drug-type-dependent response of tumor spheroids by dynamic optical coherence tomography
Authors: Abd El-Sadek Ibrahim , Morishita Rion , Mori Tomoko , Makita Shuichi , Mukherjee Pradipta , Matsusaka Satoshi , Yasuno Yoshiaki
Published: February 2024

We demonstrate label-free dynamic optical coherence tomography (D-OCT)-based visualization and quantitative assessment of patterns of tumor spheroid response to three anti-cancer drugs. The study involved treating human breast adenocarcinoma (MCF-7 cell-line) with paclitaxel (PTX), tamoxifen citrate (TAM), and doxorubicin (DOX) at concentrations of 0 (control), 0.1, 1, and 10 µM for 1, 3, and 6 days. In addition, fluorescence microscopy imaging was performed for reference. The D-OCT imaging was performed using a custom-built OCT device. Two algorithms, namely logarithmic intensity variance (LIV) and late OCT correlation decay speed (OCDS$$_l$$

l

) were used to visualize the tissue dynamics. The spheroids treated with 0.1 and 1 µM TAM appeared similar to the control spheroid, whereas those treated with 10 µM TAM had significant structural corruption and decreasing LIV and OCDS$$_l$$

l

over treatment time. The spheroids treated with PTX had decreasing volumes and decrease of LIV and OCDS$$_l$$

l

signals over time at most PTX concentrations. The spheroids treated with DOX had decreasing and increasing volumes over time at DOX concentrations of 1 and 10 µM, respectively. Meanwhile, the LIV and OCDS$$_l$$

l

signals decreased over treatment time at all DOX concentrations. The D-OCT, particularly OCDS$$_l$$

l

, patterns were consistent with the fluorescence microscopic patterns. The diversity in the structural and D-OCT results among the drug types and among the concentrations are explained by the mechanisms of the drugs. The presented results suggest that D-OCT is useful for evaluating the difference in the tumor spheroid response to different drugs and it can be a useful tool for anti-cancer drug testing.
Analysis of the carbon effect of high-standard basic farmland based on the whole life cycle
Authors: Li Xuemei , He Ying , Fu Yanhua , Wang Yajie
Published: February 2024

Based on the whole life cycle theory, the carbon effect of three different sizes of high-standard basic farmland construction projects is measured and analysed. The results show that the carbon emissions generated during the construction of high-standard basic farmland projects and the carbon absorption capacity at the later stage are different for projects of different sizes. The carbon emissions of different scales of high-standard basic farmland projects will increase during the construction stage. The results of carbon effect changes in the later operation and management stage show that the high-standard basic farmland construction projects will help reduce the carbon emissions of the field ecosystem where the farmland is located and increase its carbon sink capacity after the completion of construction, which is more obvious in larger projects. The emission reduction and carbon sequestration capacity of the farmland after remediation are improved to different degrees, which is more conducive to the ecological development of agricultural production and ecological environmental protection in the relevant areas. The study contributes to the green development of farmland, which is of some significance for the sustainable development of agriculture in Tianjin and the whole country.
Analysis of the factors influencing moderate to poor performance status in patients with cancer after chemotherapy: a cross-sectional study comparing three models
Authors: Xi Ke , Jingping Lin , Yaqing Liu , Xinyuan Yu , Hui Lin , Mei Yang , Qingyue Chen , Dun Liu
Published: February 2024

There are no models for assessing the factors that determine moderate to poor performance status in patients with cancer after chemotherapy. This study investigated the influencing factors and identified the best model for predicting moderate–poor performance status. A convenience sampling method was used. Demographic and clinical data and evaluation results for fatigue, pain, quality of life and Eastern Cooperative Oncology Group status were collected three days after the end of chemotherapy. Decision tree, random forest and logistic regression models were constructed. Ninety-four subjects in the case group had moderate to poor performance status, and 365 subjects in the control group had no or mild activity disorders. The random forest model was the most accurate model. Physical function, total protein, general quality of life within one week before chemotherapy, hemoglobin, pain symptoms and globulin were the main factors. Total protein and hemoglobin levels reflect nutritional status, and globulin levels are an index of liver function. Therefore, physical function, nutritional status, general quality of life and pain symptoms within one week before chemotherapy and liver function can be used to predict moderate–poor performance status. Nurses should pay more attention to patients with poor physical function, poor nutritional status, lower quality of life and pain symptoms after chemotherapy.
Development of tight junction-strengthening compounds using a high-throughput screening system to evaluate cell surface-localized claudin-1 in keratinocytes
Authors: Sakamoto Hiroki , Nishikawa Momoyo , Yamada Seigo
Published: February 2024

Tight junctions (TJs) are important factors constituting the physical barriers of the skin, and their suppression has been described in various conditions, such as aged skin and atopic dermatitis lesions. However, the methods for improving skin TJ function remain insufficient. Therefore, to obtain compounds that can improve TJ function, we developed a novel high-throughput screening system termed live-cell immunostaining to evaluate cell surface-localized claudin-1 (CLDN1) with high selectivity using normal human epidermal keratinocytes (NHEKs). Heparinoid and phospho-pyridoxal (p-Pyr), a metabolite of pyridoxine, were identified as hit compounds. In addition, heparinoid was strongly suggested to increase CLDN1 expression by inhibiting epidermal growth factor receptor signaling. By contrast, p-Pyr did not enhance CLDN1 expression, but it accelerated the translocation of CLDN1 to the cell surface. Finally, we confirmed that heparinoid and p-Pyr improved barrier function in NHEKs in a transepithelial electrical resistance assay. In conclusion, heparinoid and p-Pyr could potentially ameliorate skin conditions by improving TJ function.
The safety and efficacy of intra-arterial low-dose tirofiban administration during endovascular therapy in patients with large ischemic core volume
Authors: Cho Kwang-Chun , Son Nak-Hoon , Gwon So Hyeon , Choi Jin Wook , Jung Woo Sang
Published: February 2024

This study aimed to evaluate the safety and efficacy of intra-arterial (IA) administration of low- dose tirofiban during endovascular therapy in patients with large ischemic core volumes on initial brain CT. Patients were divided into two groups based on the use of IA tirofiban. We identified 87 patients (16 and 71 patients in the tirofiban and no-tirofiban groups, respectively) with acute ischemic stroke due to intracranial artery occlusion who underwent endovascular therapy with a low Alberta Stroke Program Early CT scores (2–5). Multivariate logistic regression analysis revealed no association between IA tirofiban administration and serious postprocedural hemorrhagic complications (adjusted odds ratio (aOR), 0.720; 95% confidence interval (CI) 0.099–5.219; p = 0.960), any radiologic hemorrhage (aOR 0.076; 95% CI 0.003–2.323; p = 0.139), or 3-month mortality (aOR, 0.087; 95% CI 0.005–1.501; p = 0.093). However, IA tirofiban was associated with a lower 90-day mRS score (aOR, 0.197; 95% CI 0.015–1.306; p = 0.017) and change of NIHSS compared with baseline (aOR, 0.698; 95% CI 0.531–0.917; p = 0.010). IA tirofiban administration during endovascular therapy in patients with large ischemic core volumes may be effective and safe.
Impact of pH-adjusted fluoride and stannous solutions on the protective properties on the pellicle layer in vitro and in situ
Authors: Johannes N. , Hertel S. , Stoffel V. , Hannig C. , Basche S. , Schmitt V. , Flemming J. , Hannig M.
Published: February 2024

This study evaluates the ideal pH for anti-erosion and anti-adherent efficacy of fluoride and stannous solutions (sodium fluoride (SF), amine fluoride (AF), sodium monofluorophosphate (SMFP), stannous fluoride (SnF2) with 500 ppm fluoride concentration each and stannous chloride (SnCl2, 1563 ppm stannous)). In vitro, solutions were tested at pH 4.5 and 5.5. The main in situ experiments were carried out at the pH of 4.5: For pellicle formation 6 volunteers wore bovine enamel slabs intraorally for 1 min, rinsed with 8 ml solution for 1 min and continued for up to 30 min/8 h. Physiological pellicle samples served as controls. After incubation in HCl (2.0, 2.3) for 2 min mineral release was determined photometrically. Bacterial counts on 8 h biofilms were determined by fluorescence microscopy (BacLight™ and DAPI with Concanavalin A). Modification of the pellicle ultrastructure was examined by TEM. Statistical analysis was performed using Kruskal–Wallis and Mann–Whitney-U tests with Bonferroni-correction (p < 0.05). SnF2 showed a significant erosion protection. AF, SnF2, and SnCl2 were most anti-adherent. SnF2 and SnCl2 caused a pronounced basal pellicle with stannous precipitates. Compared to other fluoride monosubstances, stannous ions offer greater protection against erosive acidic attacks. Stannous ions act as crucial co-factor in this process.
Correlations of SDF-1ɑ and XRCC1 gene polymorphisms with the risk of renal cancer development and bioinformatics studies of SDF-1α and XRCC1 and the prognosis of renal cancer
Authors: Zhang Wenjing , Su Yubo , Yue Genquan , Zhao Lingyan , Li Hailing , Jia Min , Wang Yuqi , Liu Dongyang , Wang Haisheng , Gao Yumin
Published: February 2024

To study the relationships between stromal cell-derived factor-1 (SDF-1ɑ) and renal cell carcinoma (RCC) susceptibility and the presence of single nucleotide polymorphisms in the human X-ray cross-complementary repair gene (XRCC1). Compare SDF-1 based on RCC related data in the TCGA database α, The expression difference of XRCC1 between RCC tissue and normal tissue; Collect 166 newly diagnosed RCC cases and 166 healthy individuals who underwent physical examinations during the same period, and detect genotype using iMLDR method. The results The rs1801157 locus (C:T) of the SDF-1α gene was not significantly associated with the pathohistological type, the rs1799782 locus (G:A) of the XRCC1 gene was associated with the pathohistological type of RCC, and there were interactions between rs1799782 and smoking, alcohol consumption, pesticide exposure, hair dye, and urine holding. The rs1799782 locus of the XRCC1 gene may be a key factor in the pathogenesis and pathological development of RCC. High SDF-1ɑ expression is a protective factor for the overall survival of patients with RCC, and SDF-1ɑ and XRCC1 may be important for the treatment of RCC.
Multi-omics analysis of a fatty liver model using human hepatocyte chimeric mice
Authors: Ichikawa Akemi , Miki Daiki , Hayes C. Nelson , Teraoka Yuji , Nakahara Hikaru , Tateno Chise , Ishida Yuji , Chayama Kazuaki , Oka Shiro
Published: February 2024

We developed a fatty liver mouse model using human hepatocyte chimeric mice. As transplanted human hepatocytes do not respond to mouse growth hormone (GH) and tend to accumulate fat, we hypothesized that addition of human GH would alter lipid metabolism and reduce accumulation of fat in the liver even when fed a high-fat diet. Six uPA/SCID chimeric mice were fed a high-fat GAN diet to induce fatty liver while six were fed a normal CRF1 diet, and GH was administered to three mice in each group. The mice were euthanized at 8 weeks, and human hepatocytes were extracted for RNA-Seq, DIA proteomics, and metabolomics analysis. Abdominal echocardiography revealed that the degree of fatty liver increased significantly in mice fed GAN diet (p < 0.001) and decreased significantly in mice treated with GH (p = 0.026). Weighted gene correlation network analysis identified IGF1 and SEMA7A as eigengenes. Administration of GH significantly reduced triglyceride levels and was strongly associated with metabolism of amino acids. MiBiOmics analysis identified perilipin-2 as a co-inertia driver. Results from multi-omics analysis revealed distinct gene expression and protein/metabolite profiles in each treatment group when mice were fed a high-fat or normal diet with or without administration of GH.
Developmental loss of NMDA receptors results in supernumerary forebrain neurons through delayed maturation of transit-amplifying neuroblasts
Authors: Napoli Amalia J. , Laderwager Stephanie , Zoodsma Josiah D. , Biju Bismi , Mucollari Olgerta , Schubel Sarah K. , Aprea Christieann , Sayed Aaliya , Morgan Kiele , Napoli Annelysia , Flanagan Stephanie , Wollmuth Lonnie P. , Sirotkin Howard I.
Published: February 2024

Developmental neurogenesis is a tightly regulated spatiotemporal process with its dysregulation implicated in neurodevelopmental disorders. NMDA receptors are glutamate-gated ion channels that are widely expressed in the early nervous system, yet their contribution to neurogenesis is poorly understood. Notably, a variety of mutations in genes encoding NMDA receptor subunits are associated with neurodevelopmental disorders. To rigorously define the role of NMDA receptors in developmental neurogenesis, we used a mutant zebrafish line (grin1−/−) that lacks all NMDA receptors yet survives to 10 days post-fertilization, offering the opportunity to study post-embryonic neurodevelopment in the absence of NMDA receptors. Focusing on the forebrain, we find that these fish have a progressive supernumerary neuron phenotype confined to the telencephalon at the end of embryonic neurogenesis, but which extends to all forebrain regions during postembryonic neurogenesis. This enhanced neuron population does not arise directly from increased numbers or mitotic activity of radial glia cells, the principal neural stem cells. Rather, it stems from a lack of timely maturation of transit-amplifying neuroblasts into post-mitotic neurons, as indicated by a decrease in expression of the ontogenetically-expressed chloride transporter, KCC2. Pharmacological blockade with MK-801 recapitulates the grin1−/− supernumerary neuron phenotype, indicating a requirement for ionotropic signaling. Thus, NMDA receptors are required for suppression of indirect, transit amplifying cell-driven neurogenesis by promoting maturational termination of mitosis. Loss of suppression results in neuronal overpopulation that can fundamentally change brain circuitry and may be a key factor in pathogenesis of neurodevelopmental disorders caused by NMDA receptor dysfunction.
Neuroimaging-based evidence for sympathetic correlation between brain activity and peripheral vasomotion during pain anticipation
Authors: Xu Ziqiang , Soh Zu , Kurota Yuta , Kimura Yuya , Hirano Harutoyo , Sasaoka Takafumi , Yoshino Atsuo , Tsuji Toshio
Published: February 2024

Anticipation of pain engenders anxiety and fear, potentially shaping pain perception and governing bodily responses such as peripheral vasomotion through the sympathetic nervous system (SNS). Sympathetic innervation of vascular tone during pain perception has been quantified using a peripheral arterial stiffness index; however, its innervation role during pain anticipation remains unclear. This paper reports on a neuroimaging-based study designed to investigate the responsivity and attribution of the index at different levels of anticipatory anxiety and pain perception. The index was measured in a functional magnetic resonance imaging experiment that randomly combined three visual anticipation cues and painful stimuli of two intensities. The peripheral and cerebral responses to pain anticipation and perception were quantified to corroborate bodily responsivity, and their temporal correlation was also assessed to identify the response attribution of the index. Contrasting with the high responsivity across levels of pain sensation, a low responsivity of the index across levels of anticipatory anxiety revealed its specificity across pain experiences. Discrepancies between the effects of perception and anticipation were validated across regions and levels of brain activity, providing a brain basis for peripheral response specificity. The index was also characterized by a 1-s lag in both anticipation and perception of pain, implying top-down innervation of the periphery. Our findings suggest that the SNS responds to pain in an emotion-specific and sensation-unbiased manner, thus enabling an early assessment of individual pain perception using this index. This study integrates peripheral and cerebral hemodynamic responses toward a comprehensive understanding of bodily responses to pain.
Nrf2-mediated redox balance alleviates LPS-induced vascular endothelial cell inflammation by inhibiting endothelial cell ferroptosis
Authors: Hou Huimin , Qin Xiujiao , Li Gaokai , Cui Zhitao , Zhang Jin , Dong Bin , Wang Zhicheng , Zhao Huiying
Published: February 2024

Ferroptosis plays an important role in inflammation and oxidative stress. Whether ferroptosis is involved in the inflammation of vascular endothelial cells and its regulation mechanism remains unclear. We estimated the correlation between serum iron ion levels and the inflammation index of 33 patients with arteriosclerosis. In vitro, HUVECs with or without ferrostatin-1 were exposed to Lipopolysaccharide. Corresponding cell models to verify the target signaling pathway. The results showed that serum iron ion levels had a significant positive correlation with N ratio, N/L, LDL level, and LDL/HDL (P < 0.05), and a negative correlation with L ratio (P < 0.05) in the arteriosclerosis patients. In vitro, ferroptosis is involved in HUVECs inflammation. Ferrostatin-1 can rescue LPS-induced HUVECs inflammation by decreasing HMGB1/IL-6/TNF-α expression. Nrf2 high expression could protect HUVECs against ferroptosis by activating the GPX4/GSH system, inhibiting ferritinophagy, and alleviating inflammation in HUVECs by inhibiting HMGB1/IL-6/TNF-α expression. It also found that Nrf2 is a key adaptive regulatory factor in the oxidative damage of HUVECs induced by NOX4 activation. These findings indicated that ferroptosis contributed to the pathogenesis of vascular endothelial cell damage by mediating endothelial cell inflammation. Nrf2-mediated redox balance in vascular inflammation may be a therapeutic strategy in vascular diseases.
Investigating the genetic makeup of the major histocompatibility complex (MHC) in the United Arab Emirates population through next-generation sequencing
Authors: Marzouka Nour al dain , Alnaqbi Halima , Al-Aamri Amira , Tay Guan , Alsafar Habiba
Published: February 2024

The Human leukocyte antigen (HLA) molecules are central to immune response and have associations with the phenotypes of various diseases and induced drug toxicity. Further, the role of HLA molecules in presenting antigens significantly affects the transplantation outcome. The objective of this study was to examine the extent of the diversity of HLA alleles in the population of the United Arab Emirates (UAE) using Next-Generation Sequencing methodologies and encompassing a larger cohort of individuals. A cohort of 570 unrelated healthy citizens of the UAE volunteered to provide samples for Whole Genome Sequencing and Whole Exome Sequencing. The definition of the HLA alleles was achieved through the application of the bioinformatics tools, HLA-LA and xHLA. Subsequently, the findings from this study were compared with other local and international datasets. A broad range of HLA alleles in the UAE population, of which some were previously unreported, was identified. A comparison with other populations confirmed the current population’s unique intertwined genetic heritage while highlighting similarities with populations from the Middle East region. Some disease-associated HLA alleles were detected at a frequency of > 5%, such as HLA-B*51:01, HLA-DRB1*03:01, HLA-DRB1*15:01, and HLA-DQB1*02:01. The increase in allele homozygosity, especially for HLA class I genes, was identified in samples with a higher level of genome-wide homozygosity. This highlights a possible effect of consanguinity on the HLA homozygosity. The HLA allele distribution in the UAE population showcases a unique profile, underscoring the need for tailored databases for traditional activities such as unrelated transplant matching and for newer initiatives in precision medicine based on specific populations. This research is part of a concerted effort to improve the knowledge base, particularly in the fields of transplant medicine and investigating disease associations as well as in understanding human migration patterns within the Arabian Peninsula and surrounding regions.
High brightness and low operating voltage CsPbBr3 perovskite LEDs by single-source vapor deposition
Authors: Yeh Kuan-Chi , Chan Chia-Hua
Published: February 2024

In this work, we utilized CsPbBr3 powder as the precursor material for the single-source vapor deposition (SSVD) process to fabricate the CsPbBr3 emitting layer. Due to the high density of grain boundaries and defects in the thin films deposited in the initial stages, non-radiative recombination can occur, reducing the efficiency of perovskite light-emitting diodes (PeLED). To address this issue, we employed a thermal annealing process by subjecting the perovskite films to the appropriate annealing temperature, facilitating the coalescence and growth of different grains, improving lattice integrity, and thereby reducing the presence of defects and enhancing the photoluminescence performance of the films. Furthermore, in this study, we successfully fabricated simple-structured CsPbBr3 PeLED using thermally annealed CsPbBr3 films. Among these components, even without adding the electron and hole transport layers, the best-performing device achieved a maximum brightness of 14,079 cd/m2 at a driving voltage of only 2.92 V after annealing at 350 °C; the brightness is 16.8 times higher than that of CsPbBr3 PeLED without heat treatment, demonstrating outstanding light-emitting performance. The research results show that using SSVD to prepare CsPbBr3 PeLED has broad application potential, providing a simple process option for research on improving the performance of PeLED.
Immunological characterization of a long-lasting response in a patient with metastatic triple-negative breast cancer treated with PD-1 and LAG-3 blockade
Authors: Rivoltini Licia , Camisaschi Chiara , Fucà Giovanni , Paolini Biagio , Vergani Barbara , Beretta Valeria , Damian Silvia , Duca Matteo , Cresta Sara , Magni Michele , Leone Biagio Eugenio , Castelli Chiara , de Braud Filippo , De Santis Francesca , Di Nicola Massimo
Published: February 2024

In patients with advanced triple-negative breast cancer (TNBC), translational research efforts are needed to improve the clinical efficacy of immunotherapy with checkpoint inhibitors. Here, we report on the immunological characterization of an exceptional, long-lasting, tumor complete response in a patient with metastatic TNBC treated with dual PD-1 and LAG-3 blockade within the phase I/II study CLAG525X2101C (NCT02460224) The pre-treatment tumor biopsy revealed the presence of a CD3+ and CD8+ cell infiltrate, with few PD1+ cells, rare CD4+ cells, and an absence of both NK cells and LAG3 expression. Conversely, tumor cells exhibited positive staining for the three primary LAG-3 ligands (HLA-DR, FGL-1, and galectin-3), while being negative for PD-L1. In peripheral blood, baseline expression of LAG-3 and PD-1 was observed in circulating immune cells. Following treatment initiation, there was a rapid increase in proliferating granzyme-B+ NK and T cells, including CD4+ T cells, alongside a reduction in myeloid-derived suppressor cells. The role of LAG-3 expression on circulating NK cells, as well as the expression of LAG-3 ligands on tumor cells and the early modulation of circulating cytotoxic CD4+ T cells warrant further investigation as exploitable predictive biomarkers for dual PD-1 and LAG-3 blockade.

Trial registration: NCT02460224. Registered 02/06/2015.
Ready-to-transfer two-dimensional materials using tunable adhesive force tapes
Authors: Nakatani Maki , Fukamachi Satoru , Solís-Fernández Pablo , Honda Satoshi , Kawahara Kenji , Tsuji Yuta , Sumiya Yosuke , Kuroki Mai , Li Kou , Liu Qiunan , Lin Yung-Chang , Uchida Aika , Oyama Shun , Ji Hyun Goo , Okada Kenichi , Suenaga Kazu , Kawano Yukio , Yoshizawa Kazunari , Yasui Atsushi , Ago Hiroki
Published: February 2024

Graphene and other two-dimensional (2D) materials can be used to create electronic and optoelectronic devices. However, their development has been limited by the lack of effective large-area transfer processes. Here we report a transfer method that uses functional tapes with adhesive forces controlled by ultraviolet light. The adhesion of the tape is optimized for the transfer of monolayer graphene, providing a yield of over 99%. Once detached from the growth substrate, the graphene/tape stack enables easy transfer of graphene to the desired target substrate. The method can be used to transfer other 2D materials, including bilayer graphene, transition metal dichalcogenides, hexagonal boron nitride and stacked heterostructures. The solvent-free nature of the final release step facilitates transfer to various target substrates including flexible polymers, paper and three-dimensional surfaces. The tape/2D material stacks can also be cut into desired sizes and shapes, allowing site-selective device fabrication with reduced loss of 2D materials.
Functional analysis of Cdc20 reveals a critical role of CRY box in mitotic checkpoint signaling
Authors: Zhang Yuqing , Young Rose , Garvanska Dimitriya H. , Song Chunlin , Zhai Yujing , Wang Ying , Jiang Hongfei , Fang Jing , Nilsson Jakob , Alfieri Claudio , Zhang Gang
Published: February 2024

Accurate mitosis is coordinated by the spindle assembly checkpoint (SAC) through the mitotic checkpoint complex (MCC), which inhibits the anaphase-promoting complex or cyclosome (APC/C). As an essential regulator, Cdc20 promotes mitotic exit through activating APC/C and monitors kinetochore-microtubule attachment through activating SAC. Cdc20 requires multiple interactions with APC/C and MCC subunits to elicit these functions. Functionally assessing these interactions within cells requires efficient depletion of endogenous Cdc20, which is highly difficult to achieve by RNA interference (RNAi). Here we generated Cdc20 RNAi-sensitive cell lines which display a penetrant metaphase arrest by a single RNAi treatment. In this null background, we accurately measured the contribution of each known motif of Cdc20 on APC/C and SAC activation. The CRY box, a previously identified degron, was found critical for SAC by promoting MCC formation and its interaction with APC/C. These data reveal additional regulation within the SAC and establish a novel method to interrogate Cdc20.
Mechanistic model of radiotherapy-induced lung fibrosis using coupled 3D agent-based and Monte Carlo simulations
Authors: Cogno Nicolò , Bauer Roman , Durante Marco
Published: February 2024

Background

Mechanistic modelling of normal tissue toxicities is unfolding as an alternative to the phenomenological normal tissue complication probability models. The latter, currently used in the clinics, rely exclusively on limited patient data and neglect spatial dose distribution information. Among the various approaches, agent-based models are appealing as they provide the means to include patient-specific parameters and simulate long-term effects in complex systems. However, Monte Carlo tools remain the state-of-the-art for modelling radiation transport and provide measurements of the delivered dose with unmatched precision.

Methods

In this work, we develop and characterize a coupled 3D agent-based – Monte Carlo model that mechanistically simulates the onset of the radiation-induced lung fibrosis in an alveolar segment. To the best of our knowledge, this is the first such model.

Results

Our model replicates extracellular matrix patterns, radiation-induced lung fibrosis severity indexes and functional subunits survivals that show qualitative agreement with experimental studies and are consistent with our past results. Moreover, in accordance with experimental results, higher functional subunits survival and lower radiation-induced lung fibrosis severity indexes are achieved when a 5-fractions treatment is simulated. Finally, the model shows increased sensitivity to more uniform protons dose distributions with respect to more heterogeneous ones from photon irradiation.

Conclusions

This study lays thus the groundwork for further investigating the effects of different radiotherapeutic treatments on the onset of radiation-induced lung fibrosis via mechanistic modelling.
Deep learning-based optical coherence tomography angiography image construction using spatial vascular connectivity network
Authors: Le David , Son Taeyoon , Kim Tae-Hoon , Adejumo Tobiloba , Abtahi Mansour , Ahmed Shaiban , Rossi Alfa , Ebrahimi Behrouz , Dadzie Albert , Ma Guangying , Lim Jennifer I. , Yao Xincheng
Published: February 2024

Optical coherence tomography angiography (OCTA) provides unrivaled capability for depth-resolved visualization of retinal vasculature at the microcapillary level resolution. For OCTA image construction, repeated OCT scans from one location are required to identify blood vessels with active blood flow. The requirement for multi-scan-volumetric OCT can reduce OCTA imaging speed, which will induce eye movements and limit the image field-of-view. In principle, the blood flow should also affect the reflectance brightness profile along the vessel direction in a single-scan-volumetric OCT. Here we report a spatial vascular connectivity network (SVC-Net) for deep learning OCTA construction from single-scan-volumetric OCT. We quantitatively determine the optimal number of neighboring B-scans as image input, we compare the effects of neighboring B-scans to single B-scan input models, and we explore different loss functions for optimization of SVC-Net. This approach can improve the clinical implementation of OCTA by improving transverse image resolution or increasing the field-of-view.
Mitochondrial outer membrane integrity regulates a ubiquitin-dependent and NF-κB-mediated inflammatory response
Authors: Vringer Esmee , Heilig Rosalie , Riley Joel S , Black Annabel , Cloix Catherine , Skalka George , Montes-Gómez Alfredo E , Aguado Aurore , Lilla Sergio , Walczak Henning , Gyrd-Hansen Mads , Murphy Daniel J , Huang Danny T , Zanivan Sara , Tait Stephen WG
Published: February 2024

Mitochondrial outer membrane permeabilisation (MOMP) is often essential for apoptosis, by enabling cytochrome c release that leads to caspase activation and rapid cell death. Recently, MOMP has been shown to be inherently pro-inflammatory with emerging cellular roles, including its ability to elicit anti-tumour immunity. Nonetheless, how MOMP triggers inflammation and how the cell regulates this remains poorly defined. We find that upon MOMP, many proteins localised either to inner or outer mitochondrial membranes are ubiquitylated in a promiscuous manner. This extensive ubiquitylation serves to recruit the essential adaptor molecule NEMO, leading to the activation of pro-inflammatory NF-κB signalling. We show that disruption of mitochondrial outer membrane integrity through different means leads to the engagement of a similar pro-inflammatory signalling platform. Therefore, mitochondrial integrity directly controls inflammation, such that permeabilised mitochondria initiate NF-κB signalling.
Towards the development of a DNA automaton: modular RNA-cleaving deoxyribozyme logic gates regulated by miRNAs
Authors: Smirnov Viktor V. , Drozd Valerya S. , Patra Christina K. , Hussein Zain , Rybalko Daria S. , Kozlova Anastasia V. , Nour Moustapha A. Y. , Zemerova Tatiana P. , Kolosova Olga S. , Kalnin Arseniy Y. , El-Deeb Ahmed A.
Published: February 2024

Researchers have developed a new riboswitch-based NOT gate, alongside various DNA logic gates, eachoptimized on a common scaffold. This advancement enhances performance and enables accurate detection of miRNAs on a molecular scale through DNA computing.
An on–off–on fluorescent probe for the detection of glyphosate based on a Cu2+-assisted squaraine dye sensor
Authors: Zhao Shuhua , Shi Lei , Zhang Xiufeng , Sun Xiaoran , Zhu Wenxuan , Yu Lijia
Published: February 2024

The fluorescence of F-0 is susceptible to quenching by Cu2+, but can be restored upon GLY complexation with Cu2+.
Hydrogen-bonded organic frameworks for membrane separation
Authors: Chen Cheng , Shen Liguo , Lin Hongjun , Zhao Dieling , Li Bisheng , Chen Banglin
Published: February 2024

This review provides a comprehensive overview of the fabrication strategies and applications of hydrogen-bonded organic frameworks in membrane separation.