bluuebunny/crossref_metadata_2025_split huggingface dataset:
Programming bacteria for multiplexed DNA detection
Authors: Cheng Yu-Yu , Chen Zhengyi , Cao Xinyun , Ross Tyler D. , Falbel Tanya G. , Burton Briana M. , Venturelli Ophelia S. 
Published: April 2023

AbstractDNA is a universal and programmable signal of living organisms. Here we develop cell-based DNA sensors by engineering the naturally competent bacterium Bacillus subtilis (B. subtilis) to detect specific DNA sequences in the environment. The DNA sensor strains can identify diverse bacterial species including major human pathogens with high specificity. Multiplexed detection of genomic DNA from different species in complex samples can be achieved by coupling the sensing mechanism to orthogonal fluorescent reporters. We also demonstrate that the DNA sensors can detect the presence of species in the complex samples without requiring DNA extraction. The modularity of the living cell-based DNA-sensing mechanism and simple detection procedure could enable programmable DNA sensing for a wide range of applications.
Supercritical fluids behave as complex networks
Authors: Simeski Filip , Ihme Matthias 
Published: April 2023

AbstractSupercritical fluids play a key role in environmental, geological, and celestial processes, and are of great importance to many scientific and engineering applications. They exhibit strong variations in thermodynamic response functions, which has been hypothesized to stem from the microstructural behavior. However, a direct connection between thermodynamic conditions and the microstructural behavior, as described by molecular clusters, remains an outstanding issue. By utilizing a first-principles-based criterion and self-similarity analysis, we identify energetically localized molecular clusters whose size distribution and connectivity exhibit self-similarity in the extended supercritical phase space. We show that the structural response of these clusters follows a complex network behavior whose dynamics arises from the energetics of isotropic molecular interactions. Furthermore, we demonstrate that a hidden variable network model can accurately describe the structural and dynamical response of supercritical fluids. These results highlight the need for constitutive models and provide a basis to relate the fluid microstructure to thermodynamic response functions.
KIAA1199 deficiency enhances skeletal stem cell differentiation to osteoblasts and promotes bone regeneration
Authors: Chen Li , Shi Kaikai , Ditzel Nicholas , Qiu Weimin , Figeac Florence , Nielsen Louise Himmelstrup Dreyer , Tencerova Michaela , Kowal Justyna Magdalena , Ding Ming , Andreasen Christina Møller , Andersen Thomas Levin , Kassem Moustapha 
Published: April 2023

AbstractUpon transplantation, skeletal stem cells (also known as bone marrow stromal or mesenchymal stem cells) can regulate bone regeneration by producing secreted factors. Here, we identify KIAA1199 as a bone marrow stromal cell-secreted factor in vitro and in vivo. KIAA1199 plasma levels of patients positively correlate with osteoporotic fracture risk and expression levels of KIAA1199 in patient bone marrow stromal cells negatively correlates with their osteogenic differentiation potential. KIAA1199-deficient bone marrow stromal cells exhibit enhanced osteoblast differentiation in vitro and ectopic bone formation in vivo. Consistently, KIAA1199 knockout mice display increased bone mass and biomechanical strength, as well as an increased bone formation rate. They also exhibit accelerated healing of surgically generated bone defects and are protected from ovariectomy-induced bone loss. Mechanistically, KIAA1199 regulates osteogenesis by inhibiting the production of osteopontin by osteoblasts, via integrin-mediated AKT and ERK-MAPK intracellular signaling. Thus, KIAA1199 is a regulator of osteoblast differentiation and bone regeneration and could be targeted for the treatment or management of low bone mass conditions.
High-density frustrated Lewis pairs based on Lamellar Nb2O5 for photocatalytic non-oxidative methane coupling
Authors: Chen Ziyu , Ye Yutao , Feng Xiaoyi , Wang Yan , Han Xiaowei , Zhu Yu , Wu Shiqun , Wang Senyao , Yang Wenda , Wang Lingzhi , Zhang Jinlong 
Published: April 2023

AbstractPhotocatalytic methane conversion requires a strong polarization environment composed of abundant activation sites with the robust stretching ability for C-H scissoring. High-density frustrated Lewis pairs consisting of low-valence Lewis acid Nb and Lewis base Nb-OH are fabricated on lamellar Nb2O5 through a thermal-reduction promoted phase-transition process. Benefitting from the planar atomic arrangement of lamellar Nb2O5, the frustrated Lewis pairs sites are highly exposed and accessible to reactants, which results in a superior methane conversion rate of 1456 μmol g−1 h−1 for photocatalytic non-oxidative methane coupling without the assistance of noble metals. The time-dependent DFT calculation demonstrates the photo-induced electron transfer from LA to LB sites enhances their intensities in a concerted way, promoting the C-H cleavage through the coupling of LA and LB. This work provides in-depth insight into designing and constructing a polarization micro-environment for photocatalytic C-H activation of methane without the assistance of noble metals.
Realizing efficient blue and deep-blue delayed fluorescence materials with record-beating electroluminescence efficiencies of 43.4%
Authors: Fu Yan , Liu Hao , Tang Ben Zhong , Zhao Zujin 
Published: April 2023

AbstractAs promising luminescent materials for organic light-emitting diodes (OLEDs), thermally activated delayed fluorescence materials are booming vigorously in recent years, but robust blue ones still remain challenging. Herein, we report three highly efficient blue and deep-blue delayed fluorescence materials comprised of a weak electron acceptor chromeno[3,2-c]carbazol-8(5H)-one with a rigid polycyclic structure and a weak electron donor spiro[acridine-9,9’-xanthene]. They hold distinguished merits of excellent photoluminescence quantum yields (99%), ultrahigh horizontal transition dipole ratios (93.6%), and fast radiative transition and reverse intersystem crossing, which furnish superb blue and deep-blue electroluminescence with Commission Internationale de I’Eclairage coordinates (CIEx,y) of (0.14, 0.18) and (0.14, 0.15) and record-beating external quantum efficiencies (ηexts) of 43.4% and 41.3%, respectively. Their efficiency roll-offs are successfully reduced by suppressing triplet-triplet and singlet-singlet annihilations. Moreover, high-performance deep-blue and green hyperfluorescence OLEDs are achieved by utilizing these materials as sensitizers for multi-resonance delayed fluorescence dopants, providing state-of-the-artηexts of 32.5% (CIEx,y = 0.14, 0.10) and 37.6% (CIEx,y = 0.32, 0.64), respectively, as well as greatly advanced operational lifetimes. These splendid results can surely inspire the development of blue and deep-blue luminescent materials and devices.
Type I interferon shapes brain distribution and tropism of tick-borne flavivirus
Authors: Chotiwan Nunya , Rosendal Ebba , Willekens Stefanie M. A. , Schexnaydre Erin , Nilsson Emma , Lindqvist Richard , Hahn Max , Mihai Ionut Sebastian , Morini Federico , Zhang Jianguo , Ebel Gregory D. , Carlson Lars-Anders , Henriksson Johan , Ahlgren Ulf , Marcellino Daniel , Överby Anna K. 
Published: April 2023

AbstractViral tropism within the brain and the role(s) of vertebrate immune response to neurotropic flaviviruses infection is largely understudied. We combine multimodal imaging (cm-nm scale) with single nuclei RNA-sequencing to study Langat virus in wildtype and interferon alpha/beta receptor knockout (Ifnar–/–) mice to visualize viral pathogenesis and define molecular mechanisms. Whole brain viral infection is imaged by Optical Projection Tomography coregistered to ex vivo MRI. Infection is limited to grey matter of sensory systems in wildtype mice, but extends into white matter, meninges and choroid plexus in Ifnar–/– mice. Cells in wildtype display strong type I and II IFN responses, likely due to Ifnb expressing astrocytes, infiltration of macrophages and Ifng-expressing CD8+ NK cells, whereas in Ifnar–/–, the absence of this response contributes to a shift in cellular tropism towards non-activated resident microglia. Multimodal imaging-transcriptomics exemplifies a powerful way to characterize mechanisms of viral pathogenesis and tropism.
Organic matter degradation causes enrichment of organic pollutants in hadal sediments
Authors: Sobek Anna , Abel Sebastian , Sanei Hamed , Bonaglia Stefano , Li Zhe , Horlitz Gisela , Rudra Arka , Oguri Kazumasa , Glud Ronnie N. 
Published: April 2023

AbstractBurial of persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) in deep-sea sediments contributes to 60% of their historical emissions. Yet, empirical data on their occurrence in the deep-ocean is scarce. Estimates of the deep-ocean POP sink are therefore uncertain. Hadal trenches, representing the deepest part of the ocean, are hotspots for organic carbon burial and decomposition. POPs favorably partition to organic carbon, making trenches likely significant sinks for contaminants. Here we show that PCBs occur in both hadal (7720–8085 m) and non-hadal (2560–4050 m) sediment in the Atacama Trench. PCB concentrations normalized to sediment dry weight were similar across sites while those normalized to sediment organic carbon increased exponentially as the inert organic carbon fraction of the sediment increased in degraded hadal sediments. We suggest that the unique deposition dynamics and elevated turnover of organic carbon in hadal trenches increase POP concentrations in the deepest places on Earth.
Restoring bone marrow niche function rejuvenates aged hematopoietic stem cells by reactivating the DNA Damage Response
Authors: Ramalingam Pradeep , Gutkin Michael C. , Poulos Michael G. , Tillery Taylor , Doughty Chelsea , Winiarski Agatha , Freire Ana G. , Rafii Shahin , Redmond David , Butler Jason M. 
Published: April 2023

AbstractAging associated defects within stem cell-supportive niches contribute towards age-related decline in stem cell activity. However, mechanisms underlying age-related niche defects, and whether restoring niche function can improve stem cell fitness, remain unclear. Here, we sought to determine whether aged blood stem cell function can be restored by rejuvenating their supportive niches within the bone marrow (BM). We identify Netrin-1 as a critical regulator of BM niche cell aging. Niche-specific deletion of Netrin-1 induces premature aging phenotypes within the BM microenvironment, while supplementation of aged mice with Netrin-1 rejuvenates aged niche cells and restores competitive fitness of aged blood stem cells to youthful levels. We show that Netrin-1 plays an essential role in maintaining active DNA damage responses (DDR), and that aging-associated decline in niche-derived Netrin-1 results in DNA damage accumulation within the BM microenvironment. We show that Netrin-1 supplementation is sufficient to resolve DNA damage and restore regenerative potential of the aged BM niche and blood stem cells to endure serial chemotherapy regimens.
Hypoimmune anti-CD19 chimeric antigen receptor T cells provide lasting tumor control in fully immunocompetent allogeneic humanized mice
Authors: Hu Xiaomeng , Manner Karl , DeJesus Rowena , White Kathy , Gattis Corie , Ngo Priscilla , Bandoro Christopher , Tham Eleonore , Chu Elaine Y. , Young Chi , Wells Frank , Basco Ronald , Friera Annabelle , Kangeyan Divy , Beauchesne Pascal , Dowdle William E. , Deuse Tobias , Fry Terry J. , Foster Aaron E. , Schrepfer Sonja 
Published: April 2023

AbstractManufacturing autologous chimeric antigen receptor (CAR) T cell therapeutics is complex, and many patients experience treatment delays or cannot be treated at all. Although current allogeneic CAR products have the potential to overcome manufacturing bottlenecks, they are subject to immune rejection and failure to persist in the host, and thus do not provide the same level of efficacy as their autologous counterparts. Here, we aimed to develop universal allogeneic CAR T cells that evade the immune system and produce a durable response. We generated human hypoimmune (HIP) T cells with disrupted B2M, CIITA, and TRAC genes using CRISPR-Cas9 editing. In addition, CD47 and anti-CD19 CAR were expressed using lentiviral transduction. These allogeneic HIP CD19 CAR T cells were compared to allogeneic CD19 CAR T cells that only expressed the anti-CD19 CAR (allo CAR T). In vitro assays for cancer killing and exhaustion revealed no differences between allo CAR T and HIP CAR T cells, confirming that the HIP edits did not negatively affect T cell performance. Clearance of CD19+ tumors by HIP CAR T cells in immunodeficient NSG mice was comparable to that of allo CAR T cells. In fully immunocompetent humanized mice, HIP CAR T cells significantly outperformed allo CAR T cells, showed improved persistence and expansion, and provided lasting cancer clearance. Furthermore, CD47-targeting safety strategies reliably and specifically eliminated HIP CAR T cells. These findings suggest that universal allogeneic HIP CAR T cell-based therapeutics might overcome the limitations associated with poor persistence of allogeneic CAR T cells and exert durable anti-tumor responses.
High-throughput identification of prefusion-stabilizing mutations in SARS-CoV-2 spike
Authors: Tan Timothy J. C. , Mou Zongjun , Lei Ruipeng , Ouyang Wenhao O. , Yuan Meng , Song Ge , Andrabi Raiees , Wilson Ian A. , Kieffer Collin , Dai Xinghong , Matreyek Kenneth A. , Wu Nicholas C. 
Published: April 2023

AbstractDesigning prefusion-stabilized SARS-CoV-2 spike is critical for the effectiveness of COVID-19 vaccines. All COVID-19 vaccines in the US encode spike with K986P/V987P mutations to stabilize its prefusion conformation. However, contemporary methods on engineering prefusion-stabilized spike immunogens involve tedious experimental work and heavily rely on structural information. Here, we establish a systematic and unbiased method of identifying mutations that concomitantly improve expression and stabilize the prefusion conformation of the SARS-CoV-2 spike. Our method integrates a fluorescence-based fusion assay, mammalian cell display technology, and deep mutational scanning. As a proof-of-concept, we apply this method to a region in the S2 domain that includes the first heptad repeat and central helix. Our results reveal that besides K986P and V987P, several mutations simultaneously improve expression and significantly lower the fusogenicity of the spike. As prefusion stabilization is a common challenge for viral immunogen design, this work will help accelerate vaccine development against different viruses.
Modelling 30-day hospital readmission after discharge for COPD patients based on electronic health records
Authors: Li Meng , Cheng Kun , Ku Keisun , Li Junlei , Hu Hao , Ung Carolina Oi Lam 
Published: April 2023

AbstractChronic Obstructive Pulmonary Disease (COPD) is the third most common chronic disease in China with frequent exacerbations, resulting in increased hospitalization and readmission rate. COPD readmission within 30 days after discharge is an important indicator of care transitions, patient’s quality of life and disease management. Identifying risk factors and improving 30-day readmission prediction help inform appropriate interventions, reducing readmissions and financial burden. This study aimed to develop a 30-day readmission prediction model using decision tree by learning from the data extracted from the electronic health record of COPD patients in Macao. Health records data of COPD inpatients from Kiang Wu Hospital, Macao, from January 1, 2018, to December 31, 2019 were reviewed and analyzed. A total of 782 hospitalizations for AECOPD were enrolled, where the 30-day readmission rate was 26.5% (207). A balanced dataset was randomly generated, where male accounted for 69.1% and mean age was 80.73 years old. Age, length of stay, history of tobacco smoking, hemoglobin, systemic steroids use, antibiotics use and number of hospital admission due to COPD in last 12 months were found to be significant risk factors for 30-day readmission of CODP patients (P < 0.01). A data-driven decision tree-based modelling approach with Bayesian hyperparameter optimization was developed. The mean precision-recall and AUC value for the classifier were 73.85, 73.7 and 0.7506, showing a satisfying prediction performance. The number of hospital admission due to AECOPD in last 12 months, smoke status and patients’ age were the top factors for 30-day readmission in Macao population.
The association between psychosocial stress, interpersonal sensitivity, social withdrawal and psychosis relapse: a systematic review
Authors: Almuqrin A. , Georgiades A. , Mouhitzadeh K. , Rubinic P. , Mechelli A. , Tognin S. 
Published: April 2023

AbstractPsychosis is associated with a high risk of relapse, with 67% of clients relapsing within one year following a first episode. In light of the high personal, social, and healthcare costs of the illness, it is paramount to understand the risk factors associated with psychosis relapse. The current systematic review aims to critically review the role of psychosocial stress in psychosis relapse in individuals with an established psychotic disorder. This review systematically searched Ovid (PsycINFO, EMBASE, MEDLINE) literature databases from inception until 28th February 2022. Sixteen studies were eligible for inclusion. Most studies found that individuals with psychosis demonstrate high levels of psychosocial stress and are more likely to be socially withdrawn compared to healthy controls or other clinical presentations. Most studies reported a statistically significant association between psychosocial stress and psychosis relapse, as well as between social withdrawal and psychosis relapse. However, no studies examined the association between high levels of interpersonal sensitivity and psychosis relapse. Individuals with psychosis tend to experience high levels of psychosocial stress and social withdrawal, and these appear to increase the risk of psychosis relapse. Due to high levels of heterogeneity within the literature, we could only conduct a narrative synthesis of the findings. Future studies would benefit from employing a meta-analytic approach.
An ancient metalloenzyme evolves through metal preference modulation
Authors: Sendra K. M. , Barwinska-Sendra A. , Mackenzie E. S. , Baslé A. , Kehl-Fie T. E. , Waldron K. J. 
Published: April 2023

AbstractEvolution creates functional diversity of proteins, the essential building blocks of all biological systems. However, studies of natural proteins sampled across the tree of life and evaluated in a single experimental system are lacking. Almost half of enzymes require metals, and metalloproteins tend to optimally utilize the physicochemical properties of a specific metal co-factor. Life must adapt to changes in metal bioavailability, including those during the transition from anoxic to oxic Earth or pathogens’ exposure to nutritional immunity. These changes can challenge the ability of metalloenzymes to maintain activity, presumptively driving their evolution. Here we studied metal-preference evolution within the natural diversity of the iron/manganese superoxide dismutase (SodFM) family of reactive oxygen species scavengers. We identified and experimentally verified residues with conserved roles in determining metal preference that, when combined with an understanding of the protein’s evolutionary history, improved prediction of metal utilization across the five SodFM subfamilies defined herein. By combining phylogenetics, biochemistry and structural biology, we demonstrate that SodFM metal utilization can be evolutionarily fine tuned by sliding along a scale between perfect manganese and iron specificities. Over the history of life, SodFM metal preference has been modulated multiple independent times within different evolutionary and ecological contexts, and can be changed within short evolutionary timeframes.
Expansion-enhanced super-resolution radial fluctuations enable nanoscale molecular profiling of pathology specimens
Authors: Kylies Dominik , Zimmermann Marina , Haas Fabian , Schwerk Maria , Kuehl Malte , Brehler Michael , Czogalla Jan , Hernandez Lola C. , Konczalla Leonie , Okabayashi Yusuke , Menzel Julia , Edenhofer Ilka , Mezher Sam , Aypek Hande , Dumoulin Bernhard , Wu Hui , Hofmann Smilla , Kretz Oliver , Wanner Nicola , Tomas Nicola M. , Krasemann Susanne , Glatzel Markus , Kuppe Christoph , Kramann Rafael , Banjanin Bella , Schneider Rebekka K. , Urbschat Christopher , Arck Petra , Gagliani Nicola , van Zandvoort Marc , Wiech Thorsten , Grahammer Florian , Sáez Pablo J. , Wong Milagros N. , Bonn Stefan , Huber Tobias B. , Puelles Victor G. 
Published: April 2023

AbstractExpansion microscopy physically enlarges biological specimens to achieve nanoscale resolution using diffraction-limited microscopy systems1. However, optimal performance is usually reached using laser-based systems (for example, confocal microscopy), restricting its broad applicability in clinical pathology, as most centres have access only to light-emitting diode (LED)-based widefield systems. As a possible alternative, a computational method for image resolution enhancement, namely, super-resolution radial fluctuations (SRRF)2,3, has recently been developed. However, this method has not been explored in pathology specimens to date, because on its own, it does not achieve sufficient resolution for routine clinical use. Here, we report expansion-enhanced super-resolution radial fluctuations (ExSRRF), a simple, robust, scalable and accessible workflow that provides a resolution of up to 25 nm using LED-based widefield microscopy. ExSRRF enables molecular profiling of subcellular structures from archival formalin-fixed paraffin-embedded tissues in complex clinical and experimental specimens, including ischaemic, degenerative, neoplastic, genetic and immune-mediated disorders. Furthermore, as examples of its potential application to experimental and clinical pathology, we show that ExSRRF can be used to identify and quantify classical features of endoplasmic reticulum stress in the murine ischaemic kidney and diagnostic ultrastructural features in human kidney biopsies.
Targeting the tumor microenvironment by liposomal Epacadostat in combination with liposomal gp100 vaccine
Authors: Tahaghoghi-Hajghorbani Sahar , Yazdani Mona , Nikpoor Amin Reza , Hatamipour Mahdi , Ajami Abolghasem , Jaafari Mahmoud Reza , Badiee Ali , Rafiei Alireza 
Published: April 2023

AbstractIndoleamine-2,3-dioxygenase (IDO1) pathway has vital role in cancer immune escape and its upregulation leads to immunosuppressive environment which is associated with poor prognosis and progression in various cancers like melanoma. Previously, we showed the antitumoral efficacy of nanoliposomal form of Epacadostat (Lip-EPA), as an IDO1 inhibitor. Herein, we used Lip-EPA as a combination approach with liposomal gp100 (Lip-gp100) anti-cancer vaccine in melanoma model. Here, we showed that B16F10 tumor express IDO1 so using Lip-EPA will enhance the efficacy of vaccine therapy. The biodistribution of ICG-labelled liposomal form of EPA showed the remarkable accumulation of drug at tumor site. In an in vivo study, Lip-EPA enhanced the antitumor efficacy of Lip-gp100 in which the IDO mRNA expression was decreased (~ fourfold) in tumor samples. Also, we identified a significant increase in the number of infiltrated T lymphocytes (p < 0.0001) with enhanced in interferon gamma (IFN-γ) production (p < 0.0001). Additionally, Lip-EPA + Lip-gp100 significantly modulated intratumoral regulatory T cells which altogether resulted in the highest delay in tumor growth (TGD = 56.54%) and increased life span (ILS > 47.36%) in treated mice. Our study demonstrated that novel combination of Lip-EPA and Lip-gp100 was effective treatment with capability of being used in further clinical studies.