bluuebunny/crossref_metadata_2025_split huggingface dataset:
Canagliflozin alleviates pulmonary hypertension by activating PPARγ and inhibiting its S225 phosphorylation
Authors: Li Xiu-chun , Zhu Xia-yan , Wang Yang-yue , Tong Shuo-lan , Chen Zhi-li , Lu Zi-yi , Zhang Jian-hao , Song Lan-lan , Wang Xing-hong , Zhang Chi , Sun Yi-han , Zhong Chu-yue , Su Li-huang , Wang Liang-xing , Huang Xiao-ying 
Published: May 2024

AbstractPulmonary hypertension (PH) is a progressive fatal disease with no cure. Canagliflozin (CANA), a novel medication for diabetes, has been found to have remarkable cardiovascular benefits. However, few studies have addressed the effect and pharmacological mechanism of CANA in the treatment of PH. Therefore, our study aimed to investigate the effect and pharmacological mechanism of CANA in treating PH. First, CANA suppressed increased pulmonary artery pressure, right ventricular hypertrophy, and vascular remodeling in both mouse and rat PH models. Network pharmacology, transcriptomics, and biological results suggested that CANA could ameliorate PH by suppressing excessive oxidative stress and pulmonary artery smooth muscle cell proliferation partially through the activation of PPARγ. Further studies demonstrated that CANA inhibited phosphorylation of PPARγ at Ser225 (a novel serine phosphorylation site in PPARγ), thereby promoting the nuclear translocation of PPARγ and increasing its ability to resist oxidative stress and proliferation. Taken together, our study not only highlighted the potential pharmacological effect of CANA on PH but also revealed that CANA-induced inhibition of PPARγ Ser225 phosphorylation increases its capacity to counteract oxidative stress and inhibits proliferation. These findings may stimulate further research and encourage future clinical trials exploring the therapeutic potential of CANA in PH treatment.
Early Inflatable penile prosthesis implantation offers superior outcomes compared to delayed insertion following ischemic priapism: a narrative review
Authors: Abou Chawareb Elia , Hammad Muhammed A. M. , Barham David W. , Lumbiganon Supanut , Azad Babak K. , Osmonov Daniar , Yafi Faysal A. 
Published: May 2024

AbstractIschemic priapism is a urological emergency which may lead to irreversible erectile dysfunction. One of the accepted treatments is penile prosthesis implantation. Given the scarcity of studies directly comparing timing of penile prosthesis insertion after ischemic priapism, consensus remains elusive. We aim to compare different studies in the literature concerning advantages and disadvantages of early versus delayed inflatable penile prosthesis following ischemic priapism. We analyzed 8 articles that investigated immediate and delayed inflatable penile prosthesis placement after ischemic priapism. Early inflatable penile prosthesis placement is associated with better outcomes, including pain relief, priapism resolution, penile shortening prevention, and quicker sexual activity resumption. However, it still carries a high risk of complications like edema, infection, and distal perforations. Delayed inflatable penile prosthesis insertion poses surgical challenges due to the potential for extensive corporal fibrosis. Comparative analyses have shown elevated complication rates in patients with ischemic priapism who undergo delayed inflatable penile prosthesis insertion, as opposed to those with early insertion. In studies reporting complications rates, the total complication rate in the early group was 3.37%, significantly lower than the delayed group (37.23%). Most studies support the superiority of early inflatable penile prosthesis placement following ischemic priapism over delayed placement. Further research is, however, needed to establish a global consensus on timing of prosthesis insertion.
Complete biosynthesis of QS-21 in engineered yeast
Authors: Liu Yuzhong , Zhao Xixi , Gan Fei , Chen Xiaoyue , Deng Kai , Crowe Samantha A. , Hudson Graham A. , Belcher Michael S. , Schmidt Matthias , Astolfi Maria C. T. , Kosina Suzanne M. , Pang Bo , Shao Minglong , Yin Jing , Sirirungruang Sasilada , Iavarone Anthony T. , Reed James , Martin Laetitia B. B. , El-Demerdash Amr , Kikuchi Shingo , Misra Rajesh Chandra , Liang Xiaomeng , Cronce Michael J. , Chen Xiulai , Zhan Chunjun , Kakumanu Ramu , Baidoo Edward E. K. , Chen Yan , Petzold Christopher J. , Northen Trent R. , Osbourn Anne , Scheller Henrik , Keasling Jay D. 
Published: May 2024

AbstractQS-21 is a potent vaccine adjuvant and remains the only saponin-based adjuvant that has been clinically approved for use in humans1,2. However, owing to the complex structure of QS-21, its availability is limited. Today, the supply depends on laborious extraction from the Chilean soapbark tree or on low-yielding total chemical synthesis3,4. Here we demonstrate the complete biosynthesis of QS-21 and its precursors, as well as structural derivatives, in engineered yeast strains. The successful biosynthesis in yeast requires fine-tuning of the host’s native pathway fluxes, as well as the functional and balanced expression of 38 heterologous enzymes. The required biosynthetic pathway spans seven enzyme families—a terpene synthase, P450s, nucleotide sugar synthases, glycosyltransferases, a coenzyme A ligase, acyl transferases and polyketide synthases—from six organisms, and mimics in yeast the subcellular compartmentalization of plants from the endoplasmic reticulum membrane to the cytosol. Finally, by taking advantage of the promiscuity of certain pathway enzymes, we produced structural analogues of QS-21 using this biosynthetic platform. This microbial production scheme will allow for the future establishment of a structure–activity relationship, and will thus enable the rational design of potent vaccine adjuvants.
Lithium tantalate photonic integrated circuits for volume manufacturing
Authors: Wang Chengli , Li Zihan , Riemensberger Johann , Lihachev Grigory , Churaev Mikhail , Kao Wil , Ji Xinru , Zhang Junyin , Blesin Terence , Davydova Alisa , Chen Yang , Huang Kai , Wang Xi , Ou Xin , Kippenberg Tobias J. 
Published: May 2024

AbstractElectro-optical photonic integrated circuits (PICs) based on lithium niobate (LiNbO3) have demonstrated the vast capabilities of materials with a high Pockels coefficient1,2. They enable linear and high-speed modulators operating at complementary metal–oxide–semiconductor voltage levels3 to be used in applications including data-centre communications4, high-performance computing and photonic accelerators for AI5. However, industrial use of this technology is hindered by the high cost per wafer and the limited wafer size. The high cost results from the lack of existing high-volume applications in other domains of the sort that accelerated the adoption of silicon-on-insulator (SOI) photonics, which was driven by vast investment in microelectronics. Here we report low-loss PICs made of lithium tantalate (LiTaO3), a material that has already been adopted commercially for 5G radiofrequency filters6 and therefore enables scalable manufacturing at low cost, and it has equal, and in some cases superior, properties to LiNbO3. We show that LiTaO3 can be etched to create low-loss (5.6 dB m−1) PICs using a deep ultraviolet (DUV) stepper-based manufacturing process7. We demonstrate a LiTaO3 Mach–Zehnder modulator (MZM) with a half-wave voltage–length product of 1.9 V cm and an electro-optic bandwidth of up to 40 GHz. In comparison with LiNbO3, LiTaO3 exhibits a much lower birefringence, enabling high-density circuits and broadband operation over all telecommunication bands. Moreover, the platform supports the generation of soliton microcombs. Our work paves the way for the scalable manufacture of low-cost and large-volume next-generation electro-optical PICs.
Discovery of potent small-molecule inhibitors of lipoprotein(a) formation
Authors: Diaz Nuria , Perez Carlos , Escribano Ana Maria , Sanz Gema , Priego Julian , Lafuente Celia , Barberis Mario , Calle Luis , Espinosa Juan Felix , Priest Birgit T. , Zhang Hong Y. , Nosie Amanda K. , Haas Joseph V. , Cannady Ellen , Borel Anthony , Schultze Albert E. , Sauder J. Michael , Hendle Jörg , Weichert Ken , Nicholls Stephen J. , Michael Laura F. 
Published: May 2024

AbstractLipoprotein(a) (Lp(a)), an independent, causal cardiovascular risk factor, is a lipoprotein particle that is formed by the interaction of a low-density lipoprotein (LDL) particle and apolipoprotein(a) (apo(a))1,2. Apo(a) first binds to lysine residues of apolipoprotein B-100 (apoB-100) on LDL through the Kringle IV (KIV) 7 and 8 domains, before a disulfide bond forms between apo(a) and apoB-100 to create Lp(a) (refs. 3–7). Here we show that the first step of Lp(a) formation can be inhibited through small-molecule interactions with apo(a) KIV7–8. We identify compounds that bind to apo(a) KIV7–8, and, through chemical optimization and further application of multivalency, we create compounds with subnanomolar potency that inhibit the formation of Lp(a). Oral doses of prototype compounds and a potent, multivalent disruptor, LY3473329 (muvalaplin), reduced the levels of Lp(a) in transgenic mice and in cynomolgus monkeys. Although multivalent molecules bind to the Kringle domains of rat plasminogen and reduce plasmin activity, species-selective differences in plasminogen sequences suggest that inhibitor molecules will reduce the levels of Lp(a), but not those of plasminogen, in humans. These data support the clinical development of LY3473329—which is already in phase 2 studies—as a potent and specific orally administered agent for reducing the levels of Lp(a).
The intrinsic substrate specificity of the human tyrosine kinome
Authors: Yaron-Barir Tomer M. , Joughin Brian A. , Huntsman Emily M. , Kerelsky Alexander , Cizin Daniel M. , Cohen Benjamin M. , Regev Amit , Song Junho , Vasan Neil , Lin Ting-Yu , Orozco Jose M. , Schoenherr Christina , Sagum Cari , Bedford Mark T. , Wynn R. Max , Tso Shih-Chia , Chuang David T. , Li Lei , Li Shawn S.-C. , Creixell Pau , Krismer Konstantin , Takegami Mina , Lee Harin , Zhang Bin , Lu Jingyi , Cossentino Ian , Landry Sean D. , Uduman Mohamed , Blenis John , Elemento Olivier , Frame Margaret C. , Hornbeck Peter V. , Cantley Lewis C. , Turk Benjamin E. , Yaffe Michael B. , Johnson Jared L. 
Published: May 2024

AbstractPhosphorylation of proteins on tyrosine (Tyr) residues evolved in metazoan organisms as a mechanism of coordinating tissue growth1. Multicellular eukaryotes typically have more than 50 distinct protein Tyr kinases that catalyse the phosphorylation of thousands of Tyr residues throughout the proteome1–3. How a given Tyr kinase can phosphorylate a specific subset of proteins at unique Tyr sites is only partially understood4–7. Here we used combinatorial peptide arrays to profile the substrate sequence specificity of all human Tyr kinases. Globally, the Tyr kinases demonstrate considerable diversity in optimal patterns of residues surrounding the site of phosphorylation, revealing the functional organization of the human Tyr kinome by substrate motif preference. Using this information, Tyr kinases that are most compatible with phosphorylating any Tyr site can be identified. Analysis of mass spectrometry phosphoproteomic datasets using this compendium of kinase specificities accurately identifies specific Tyr kinases that are dysregulated in cells after stimulation with growth factors, treatment with anti-cancer drugs or expression of oncogenic variants. Furthermore, the topology of known Tyr signalling networks naturally emerged from a comparison of the sequence specificities of the Tyr kinases and the SH2 phosphotyrosine (pTyr)-binding domains. Finally we show that the intrinsic substrate specificity of Tyr kinases has remained fundamentally unchanged from worms to humans, suggesting that the fidelity between Tyr kinases and their protein substrate sequences has been maintained across hundreds of millions of years of evolution.
Accurate structure prediction of biomolecular interactions with AlphaFold 3
Authors: Abramson Josh , Adler Jonas , Dunger Jack , Evans Richard , Green Tim , Pritzel Alexander , Ronneberger Olaf , Willmore Lindsay , Ballard Andrew J. , Bambrick Joshua , Bodenstein Sebastian W. , Evans David A. , Hung Chia-Chun , O’Neill Michael , Reiman David , Tunyasuvunakool Kathryn , Wu Zachary , Žemgulytė Akvilė , Arvaniti Eirini , Beattie Charles , Bertolli Ottavia , Bridgland Alex , Cherepanov Alexey , Congreve Miles , Cowen-Rivers Alexander I. , Cowie Andrew , Figurnov Michael , Fuchs Fabian B. , Gladman Hannah , Jain Rishub , Khan Yousuf A. , Low Caroline M. R. , Perlin Kuba , Potapenko Anna , Savy Pascal , Singh Sukhdeep , Stecula Adrian , Thillaisundaram Ashok , Tong Catherine , Yakneen Sergei , Zhong Ellen D. , Zielinski Michal , Žídek Augustin , Bapst Victor , Kohli Pushmeet , Jaderberg Max , Hassabis Demis , Jumper John M. 
Published: May 2024

AbstractThe introduction of AlphaFold 21 has spurred a revolution in modelling the structure of proteins and their interactions, enabling a huge range of applications in protein modelling and design2–6. Here we describe our AlphaFold 3 model with a substantially updated diffusion-based architecture that is capable of predicting the joint structure of complexes including proteins, nucleic acids, small molecules, ions and modified residues. The new AlphaFold model demonstrates substantially improved accuracy over many previous specialized tools: far greater accuracy for protein–ligand interactions compared with state-of-the-art docking tools, much higher accuracy for protein–nucleic acid interactions compared with nucleic-acid-specific predictors and substantially higher antibody–antigen prediction accuracy compared with AlphaFold-Multimer v.2.37,8. Together, these results show that high-accuracy modelling across biomolecular space is possible within a single unified deep-learning framework.
Effects of a personalized nutrition program on cardiometabolic health: a randomized controlled trial
Authors: Bermingham Kate M. , Linenberg Inbar , Polidori Lorenzo , Asnicar Francesco , Arrè Alberto , Wolf Jonathan , Badri Fatema , Bernard Hannah , Capdevila Joan , Bulsiewicz William J. , Gardner Christopher D. , Ordovas Jose M. , Davies Richard , Hadjigeorgiou George , Hall Wendy L. , Delahanty Linda M. , Valdes Ana M. , Segata Nicola , Spector Tim D. , Berry Sarah E. 
Published: May 2024

AbstractLarge variability exists in people’s responses to foods. However, the efficacy of personalized dietary advice for health remains understudied. We compared a personalized dietary program (PDP) versus general advice (control) on cardiometabolic health using a randomized clinical trial. The PDP used food characteristics, individual postprandial glucose and triglyceride (TG) responses to foods, microbiomes and health history, to produce personalized food scores in an 18-week app-based program. The control group received standard care dietary advice (US Department of Agriculture Guidelines for Americans, 2020–2025) using online resources, check-ins, video lessons and a leaflet. Primary outcomes were serum low-density lipoprotein cholesterol and TG concentrations at baseline and at 18 weeks. Participants (n = 347), aged 41–70 years and generally representative of the average US population, were randomized to the PDP (n = 177) or control (n = 170). Intention-to-treat analysis (n = 347) between groups showed significant reduction in TGs (mean difference = −0.13 mmol l−1; log-transformed 95% confidence interval = −0.07 to −0.01, P = 0.016). Changes in low-density lipoprotein cholesterol were not significant. There were improvements in secondary outcomes, including body weight, waist circumference, HbA1c, diet quality and microbiome (beta-diversity) (P < 0.05), particularly in highly adherent PDP participants. However, blood pressure, insulin, glucose, C-peptide, apolipoprotein A1 and B, and postprandial TGs did not differ between groups. No serious intervention-related adverse events were reported. Following a personalized diet led to some improvements in cardiometabolic health compared to standard dietary advice. ClinicalTrials.gov registration: NCT05273268.
Lens-free reflective topography for high-resolution wafer inspection
Authors: Lee Hojun , Sung Jangwoon , Park Seungbeom , Shin Junho , Kim Hyungjin , Kim Wookrae , Lee Myungjun 
Published: May 2024

AbstractThe demand for high-resolution and large-area imaging systems for non-destructive wafer inspection has grown owing to the increasing complexity and extremely fine nature of semiconductor processes. Several studies have focused on developing high-resolution imaging systems; however, they were limited by the tradeoff between image resolution and field of view. Hence, computational imaging has arisen as an alternative method to conventional optical imaging, aimed at enhancing the aforementioned parameters. This study proposes a method for improving the resolution and field of view of an image in a lens-less reflection-type system. Our method was verified by computationally restoring the final image from diffraction images measured at various illumination positions using a visible light source. We introduced speckle illumination to expand the numerical aperture of the entire system, simultaneously improving image resolution and field of view. The image reconstruction process was accelerated by employing a convolutional neural network. Using the reconstructed phase images, we implemented high-resolution topography and demonstrated its applicability in wafer surface inspection. Furthermore, we demonstrated an ideal diffraction-limited spatial resolution of 1.7 μm over a field of view of 1.8 × 1.8 mm2 for the topographic imaging of targets with various surface roughness. The proposed approach is suitable for applications that simultaneously require high throughput and resolution, such as wafer-wide integrated metrology, owing to its compact design, cost-effectiveness, and mechanical robustness.
Phytochemical investigation of the n-hexane-extracted oil from four umbelliferous vegetables using GC/MS analysis in the context of antibacterial activity
Authors: Baky Mostafa H. , El-Taher Eman M. , Naggar Dina M. Y. El , Abouelela Mostafa B. 
Published: May 2024

AbstractUmbelliferous (Apiaceae) vegetables are widely consumed worldwide for their nutritive and health benefits. The main goal of the current study is to explore the compositional heterogeneity in four dried umbelliferous vegetables viz, celery, coriander, dill, and parsley targeting their volatile profile using gas chromatography-mass spectrometry (GC–MS). A total of 133 volatile metabolites were detected belonging to 12 classes. Aromatic hydrocarbons were detected as the major components of the analyzed vegetables accounting ca. 64.0, 62.4, 59.5, and 47.8% in parsley, dill, celery, and coriander, respectively. Aliphatic hydrocarbons were detected at ca. 6.39, 8.21, 6.16, and 6.79% in parsley, dill, celery, and coriander, respectively. Polyunsaturated fatty acids (PUFA) of various health benefits were detected in parsley and represented by roughanic acid and α-linolenic acid at 4.99 and 0.47%, respectively. Myristicin and frambinone were detected only in parsley at 0.45 and 0.56%. Investigation of antibacterial activity of umbelliferous vegetables n-hexane extract revealed a moderate antibacterial activity against Gram-positive and Gram-negative bacteria with higher activity for celery and dill against Staphylococcus aureus with inhibition zone 20.3 mm compared to 24.3 mm of the standard antibacterial drug.
Identification of maladaptive behavioural patterns in response to extreme weather events
Authors: Eusse-Villa Luisa , Bonardi Pellizzari Carolina , Franceschinis Cristiano , Thiene Mara , Borga Marco , Scolobig Anna 
Published: May 2024

AbstractHuman behaviour has gained recognition as a critical factor in addressing climate change and its impacts. With extreme weather events posing risks to vulnerable communities, understanding cognitive processes driving behaviours becomes essential for effective risk communication. This study focuses on the 2018 “Vaia” storm, which brought unprecedented precipitation and wind velocity to the mountainous regions of North-eastern Italy. Drawing upon the Protection Motivation Theory (PMT) framework, we employ probabilistic models to identify distinct groups with similar behavioural profiles. By administering a web-based survey to 1500 residents affected by the event, we find that threat appraisal is more influential in shaping protective behaviours than coping appraisal. Our findings indicate that by enhancing coping appraisals and discouraging non-protective measures, we can actively mitigate maladaptive responses and promote the adoption of effective adaptation strategies.
Carotenoid biosynthesis genes LcLCYB, LcLCYE, and LcBCH from wolfberry confer increased carotenoid content and improved salt tolerance in tobacco
Authors: Li Chen , Wang Caili , Cheng Zhiyang , Li Yu , Li Wenjing 
Published: May 2024

AbstractCarotenoids play essential roles in plant growth and development and provide plants with a tolerance to a series of abiotic stresses. In this study, the function and biological significance of lycopene β-cyclase, lycopene ε-cyclase, and β-carotene hydroxylase, which are responsible for the modification of the tetraterpene skeleton procedure, were isolated from Lycium chinense and analyzed. The overexpression of lycopene β-cyclase, lycopene ε-cyclase, and β-carotene hydroxylase promoted the accumulation of total carotenoids and photosynthesis enhancement, reactive oxygen species scavenging activity, and proline content of tobacco seedlings after exposure to the salt stress. Furthermore, the expression of the carotenoid biosynthesis genes and stress-related genes (ascorbate peroxidase, catalase, peroxidase, superoxide dismutase, and pyrroline-5-carboxylate reductase) were detected and showed increased gene expression level, which were strongly associated with the carotenoid content and reactive oxygen species scavenging activity. After exposure to salt stress, the endogenous abscisic acid content was significantly increased and much higher than those in control plants. This research contributes to the development of new breeding aimed at obtaining stronger salt tolerance plants with increased total carotenoids and vitamin A content.
Segmentation of mature human oocytes provides interpretable and improved blastocyst outcome predictions by a machine learning model
Authors: Fjeldstad Jullin , Qi Weikai , Siddique Nadia , Mercuri Natalie , Nayot Dan , Krivoi Alex 
Published: May 2024

AbstractWithin the medical field of human assisted reproductive technology, a method for interpretable, non-invasive, and objective oocyte evaluation is lacking. To address this clinical gap, a workflow utilizing machine learning techniques has been developed involving automatic multi-class segmentation of two-dimensional images, morphometric analysis, and prediction of developmental outcomes of mature denuded oocytes based on feature extraction and clinical variables. Two separate models have been developed for this purpose—a model to perform multiclass segmentation, and a classifier model to classify oocytes as likely or unlikely to develop into a blastocyst (Day 5–7 embryo). The segmentation model is highly accurate at segmenting the oocyte, ensuring high-quality segmented images (masks) are utilized as inputs for the classifier model (mask model). The mask model displayed an area under the curve (AUC) of 0.63, a sensitivity of 0.51, and a specificity of 0.66 on the test set. The AUC underwent a reduction to 0.57 when features extracted from the ooplasm were removed, suggesting the ooplasm holds the information most pertinent to oocyte developmental competence. The mask model was further compared to a deep learning model, which also utilized the segmented images as inputs. The performance of both models combined in an ensemble model was evaluated, showing an improvement (AUC 0.67) compared to either model alone. The results of this study indicate that direct assessments of the oocyte are warranted, providing the first objective insights into key features for developmental competence, a step above the current standard of care—solely utilizing oocyte age as a proxy for quality.