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The yeast Saccharomyces cerevisiae has been an essential component of human civilization because of its long global history of use in food and beverage fermentation. However, the diversity and evolutionary history of the domesticated populations of the yeast remain elusive. We show here that China/Far East Asia is likely the center of origin of the domesticated populations of the species. The domesticated populations form two major groups associated with solid- and liquid-state fermentation and appear to have originated from heterozygous ancestors, which were likely formed by outcrossing between diverse wild isolates primitively for adaptation to maltose-rich niches. We found consistent gene expansion and contraction in the whole domesticated population, as well as lineage-specific genome variations leading to adaptation to different environments. We show a nearly panoramic view of the diversity and life history of S. cerevisiae and provide new insights into the origin and evolution of the species. An understanding of the domestication of the yeast Saccharomyces cerevisiae has important implications for studying its evolution and diversity. Here, the authors show that Far East Asia is likely the center of origin of the domesticated populations of the yeast based on genomic and phenotypic characterization of a large collection of isolates.

Long-distance entanglement distribution is essential for both foundational tests of quantum physics and scalable quantum networks. Owing to channel loss, however, the previously achieved distance was limited to ~100 kilometers. Here we demonstrate satellite-based distribution of entangled photon pairs to two locations separated by 1203 kilometers on Earth, through two satellite-to-ground downlinks with a summed length varying from 1600 to 2400 kilometers. We observed a survival of two-photon entanglement and a violation of Bell inequality by 2.37 ± 0.09 under strict Einstein locality conditions. The obtained effective link efficiency is orders of magnitude higher than that of the direct bidirectional transmission of the two photons through telecommunication fibers.

The precise and large-scale identification of intact glycopeptides is a critical step in glycoproteomics. Owing to the complexity of glycosylation, the current overall throughput, data quality and accessibility of intact glycopeptide identification lack behind those in routine proteomic analyses. Here, we propose a workflow for the precise high-throughput identification of intact N-glycopeptides at the proteome scale using stepped-energy fragmentation and a dedicated search engine. pGlyco 2.0 conducts comprehensive quality control including false discovery rate evaluation at all three levels of matches to glycans, peptides and glycopeptides, improving the current level of accuracy of intact glycopeptide identification. The N-glycoproteome of samples metabolically labeled with 15 N/ 13 C were analyzed quantitatively and utilized to validate the glycopeptide identification, which could be used as a novel benchmark pipeline to compare different search engines. Finally, we report a large-scale glycoproteome dataset consisting of 10,009 distinct site-specific N-glycans on 1988 glycosylation sites from 955 glycoproteins in five mouse tissues. Protein glycosylation is a heterogeneous post-translational modification that generates greater proteomic diversity that is difficult to analyze. Here the authors describe pGlyco 2.0, a workflow for the precise one step identification of intact N-glycopeptides at the proteome scale.

Large language models (LLMs) are rapidly advancing medical artificial intelligence, offering revolutionary changes in health care. These models excel in natural language processing (NLP), enhancing clinical support, diagnosis, treatment, and medical research. Breakthroughs, like GPT-4 and BERT (Bidirectional Encoder Representations from Transformer), demonstrate LLMs’ evolution through improved computing power and data. However, their high hardware requirements are being addressed through technological advancements. LLMs are unique in processing multimodal data, thereby improving emergency, elder care, and digital medical procedures. Challenges include ensuring their empirical reliability, addressing ethical and societal implications, especially data privacy, and mitigating biases while maintaining privacy and accountability. The paper emphasizes the need for human-centric, bias-free LLMs for personalized medicine and advocates for equitable development and access. LLMs hold promise for transformative impacts in health care.

Bioimplant engineering strives to provide biological replacements for regenerating, retaining, or modifying injured tissues and/or organ function. Modern advanced material technology breakthroughs have aided in diversifying ingredients used in orthopaedic implant applications. As such, nanoparticles may mimic the surface features of real tissues, particularly in terms of wettability, topography, chemistry, and energy. Additionally, the new features of nanoparticles support their usage in enhancing the development of various tissues. The current study establishes the groundwork for nanotechnology-driven biomaterials by elucidating key design issues that affect the success or failure of an orthopaedic implant, its antibacterial/antimicrobial activity, response to cell attachment propagation, and differentiation. The possible use of nanoparticles (in the form of nanosized surface or a usable nanocoating applied to the implant’s surface) can solve a number of problems (i.e., bacterial adhesion and corrosion resilience) associated with conventional metallic or non-metallic implants, particularly when implant techniques are optimised. Orthopaedic biomaterials’ prospects (i.e., pores architectures, 3D implants, and smart biomaterials) are intriguing in achieving desired implant characteristics and structure exhibiting stimuli-responsive attitude. The primary barriers to commercialization of nanotechnology-based composites are ultimately discussed, therefore assisting in overcoming the constraints in relation to certain pre-existing orthopaedic biomaterials, critical factors such as quality, implant life, treatment cost, and pain alleviation.

Great advances have been made in mass spectrometric data interpretation for intact glycopeptide analysis. However, accurate identification of intact glycopeptides and modified saccharide units at the site-specific level and with fast speed remains challenging. Here, we present a glycan-first glycopeptide search engine, pGlyco3, to comprehensively analyze intact N- and O-glycopeptides, including glycopeptides with modified saccharide units. A glycan ion-indexing algorithm developed for glycan-first search makes pGlyco3 5–40 times faster than other glycoproteomic search engines without decreasing accuracy or sensitivity. By combining electron-based dissociation spectra, pGlyco3 integrates a dynamic programming-based algorithm termed pGlycoSite for site-specific glycan localization. Our evaluation shows that the site-specific glycan localization probabilities estimated by pGlycoSite are suitable to localize site-specific glycans. With pGlyco3, we confidently identified N-glycopeptides and O-mannose glycopeptides that were extensively modified by ammonia adducts in yeast samples. The freely available pGlyco3 is an accurate and flexible tool that can be used to identify glycopeptides and modified saccharide units.pGlyco3 is a glycan-first glycopeptide search engine for the identification and localization of site-specific N- and O-glycopeptides, including glycopeptides with modified glycans.

Diabetic kidney disease (DKD) is one of the microvascular complications of diabetes mellitus and a major cause of end-stage renal disease with limited treatment options. Wogonin is a flavonoid derived from the root of Scutellaria baicalensis Georgi, which has shown a potent renoprotective effect. But the mechanisms of action in DKD are not fully elucidated. In this study, we investigated the effects of wogonin on glomerular podocytes in DKD using mouse podocyte clone 5 (MPC5) cells and diabetic mice model. MPC5 cells were treated with high glucose (30 mM). We showed that wogonin (4, 8, 16 μM) dose-dependently alleviated high glucose (HG)-induced MPC5 cell damage, accompanied by increased expression of WT-1, nephrin, and podocin proteins, and decreased expression of TNF-α, MCP-1, IL-1β as well as phosphorylated p65. Furthermore, wogonin treatment significantly inhibited HG-induced apoptosis in MPC5 cells. Wogonin reversed HG-suppressed autophagy in MPC5 cells, evidenced by increased ATG7, LC3-II, and Beclin-1 protein, and decreased p62 protein. We demonstrated that wogonin directly bound to Bcl-2 in MPC5 cells. In HG-treated MPC5 cells, knockdown of Bcl-2 abolished the beneficial effects of wogonin, whereas overexpression of Bcl-2 mimicked the protective effects of wogonin. Interestingly, we found that the expression of Bcl-2 was significantly decreased in biopsy renal tissue of diabetic nephropathy patients. In vivo experiments were conducted in STZ-induced diabetic mice, which were administered wogonin (10, 20, 40 mg · kg −1  · d −1 , i.g.) every other day for 12 weeks. We showed that wogonin administration significantly alleviated albuminuria, histopathological lesions, and p65 NF-κB-mediated renal inflammatory response. Wogonin administration dose-dependently inhibited podocyte apoptosis and promoted podocyte autophagy in STZ-induced diabetic mice. This study for the first time demonstrates a novel action of wogonin in mitigating glomerulopathy and podocytes injury by regulating Bcl-2-mediated crosstalk between autophagy and apoptosis. Wogonin may be a potential therapeutic drug against DKD.

The performance of transition metal hydroxides, as cocatalysts for CO 2 photoreduction, is significantly limited by their inherent weaknesses of poor conductivity and stacked structure. Herein, we report the rational assembly of a series of transition metal hydroxides on graphene to act as a cocatalyst ensemble for efficient CO 2 photoreduction. In particular, with the Ru-dye as visible light photosensitizer, hierarchical Ni(OH) 2 nanosheet arrays-graphene (Ni(OH) 2 -GR) composites exhibit superior photoactivity and selectivity, which remarkably surpass other counterparts and most of analogous hybrid photocatalyst system. The origin of such superior performance of Ni(OH) 2 -GR is attributed to its appropriate synergy on the enhanced adsorption of CO 2 , increased active sites for CO 2 reduction and improved charge carriers separation/transfer. This work is anticipated to spur rationally designing efficient earth-abundant transition metal hydroxides-based cocatalysts on graphene and other two-dimension platforms for artificial reduction of CO 2 to solar chemicals and fuels. The development of effective, earth-abundant cocatalysts is critical for photocatalytic CO 2 reduction. Here, authors report the assembly of transition metal hydroxides on graphene to act as cocatalyst ensembles for efficient CO 2 photoreduction.

The Helically Coiled Heat Exchanger (HCHX) is a promising candidate for modular Molten Salt Reactors (MSRs), valued for its high heat transfer efficiency, structural compactness, reduced fouling tendency, and excellent thermal compensation capabilities. The thermal–hydraulic performance of the shell side, crucial for reactor efficiency and safety, requires accurate prediction. This is challenged by the scarcity of reliable correlations for high-Prandtl number fluoride salts under low-Reynolds number conditions. To address this gap, this study explores the heat transfer and flow resistance of FNaBe salt flow in an HCHX using Computational Fluid Dynamics (CFD). The validated CFD model examines the effects of structural parameters (number of layers, tube pitch, and helix angle) and inlet conditions (temperatures and velocities). It is found that the Nusselt number and friction factor increase with more layers but decrease with a higher tube pitch and helix angle. Subsequently, new empirical correlations integrating these geometric parameters are proposed, demonstrating excellent agreement with simulation results (deviations within the range of −10–5% for Nu and −5–10% for f). This study offers vital theoretical support for optimizing compact HCHX designs in MSRs.

In this paper, we study the thick brane system in the so-called f(Q) gravity, where the gravitational interaction was encoded by the nonmetricity Q like scalar curvature R in general relativity. With a special choice of f(Q)=Q-bQn, we find that the thick brane system can be solved analytically with the first-order formalism, where the complicated second-order differential equation is transformed to several first-order differential equations. Moreover, the stability of the thick brane system under tensor perturbation is also investigated. It is shown that the tachyonic states are absent and the graviton zero mode can be localized on the brane. Thus, the four-dimensional Newtonian potential can be recovered at low energy. Besides, the corrections of the massive graviton Kaluza–Klein modes to the Newtonian potential are also analyzed briefly.