bluuebunny/crossref_metadata_2025 huggingface dataset:
Glucagon-like peptide-1 receptor: mechanisms and advances in therapy
Authors: Zheng Zhikai , Zong Yao , Ma Yiyang , Tian Yucheng , Pang Yidan , Zhang Changqing , Gao Junjie
Published: September 2024

The glucagon-like peptide-1 (GLP-1) receptor, known as GLP-1R, is a vital component of the G protein-coupled receptor (GPCR) family and is found primarily on the surfaces of various cell types within the human body. This receptor specifically interacts with GLP-1, a key hormone that plays an integral role in regulating blood glucose levels, lipid metabolism, and several other crucial biological functions. In recent years, GLP-1 medications have become a focal point in the medical community due to their innovative treatment mechanisms, significant therapeutic efficacy, and broad development prospects. This article thoroughly traces the developmental milestones of GLP-1 drugs, from their initial discovery to their clinical application, detailing the evolution of diverse GLP-1 medications along with their distinct pharmacological properties. Additionally, this paper explores the potential applications of GLP-1 receptor agonists (GLP-1RAs) in fields such as neuroprotection, anti-infection measures, the reduction of various types of inflammation, and the enhancement of cardiovascular function. It provides an in-depth assessment of the effectiveness of GLP-1RAs across multiple body systems-including the nervous, cardiovascular, musculoskeletal, and digestive systems. This includes integrating the latest clinical trial data and delving into potential signaling pathways and pharmacological mechanisms. The primary goal of this article is to emphasize the extensive benefits of using GLP-1RAs in treating a broad spectrum of diseases, such as obesity, cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), neurodegenerative diseases, musculoskeletal inflammation, and various forms of cancer. The ongoing development of new indications for GLP-1 drugs offers promising prospects for further expanding therapeutic interventions, showcasing their significant potential in the medical field.
Irinotecan hydrochloride liposome HR070803 in combination with 5-fluorouracil and leucovorin in locally advanced or metastatic pancreatic ductal adenocarcinoma following prior gemcitabine-based therapy (PAN-HEROIC-1): a phase 3 trial
Authors: Cui Jiujie , Qin Shukui , Zhou Yuhong , Zhang Shuang , Sun Xiaofeng , Zhang Mingjun , Cui Jiuwei , Fang Weijia , Gu Kangsheng , Li Zhihua , Wang Jufeng , Chen Xiaobing , Yao Jun , Zhou Jun , Wang Gang , Bai Yuxian , Xiao Juxiang , Qiu Wensheng , Wang Bangmao , Xia Tao , Wang Chunyue , Kong Li , Yin Jiajun , Zhang Tao , Shen Xionghu , Fu Deliang , Gao Chuntao , Wang Huan , Wang Quanren , Wang Liwei
Published: September 2024

Liposomal irinotecan has shown promising antitumor activity in patients with advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) who have undergone prior gemcitabine-based therapies. This randomized, double-blind, parallel-controlled, multicenter phase 3 study (NCT05074589) assessed the efficacy and safety of liposomal irinotecan HR070803 combined with 5-fluorouracil (5-FU) and leucovorin (LV) in this patient population. Patients with unresectable, locally advanced, or metastatic PDAC who had previously received gemcitabine-based therapies were randomized 1:1 to receive either HR070803 (60 mg/m2 anhydrous irinotecan hydrochloride, equal to 56.5 mg/m2 free base) or placebo, both in combination with 5-FU (2000 mg/m2) and LV (200 mg/m2), all given intravenously every two weeks. The primary endpoint of the study was overall survival (OS). A total of 298 patients were enrolled and received HR070803 plus 5-FU/LV (HR070803 group, n = 149) or placebo plus 5-FU/LV (placebo group, n = 149). Median OS was significantly improved in the HR070803 group compared to the placebo group (7.4 months [95% CI 6.1–8.4] versus 5.0 months [95% CI 4.3–6.0]; HR 0.63 [95% CI 0.48–0.84]; two-sided p = 0.0019). The most common grade ≥ 3 adverse events in the HR070803 group were increased gamma-glutamyltransferase (19.0% versus 11.6% in placebo group) and decreased neutrophil count (12.9% versus 0 in placebo group). No treatment-related deaths occurred in the HR070803 group, while the placebo group reported one treatment-related death (abdominal infection). HR070803 in combination with 5-FU/LV has shown promising efficacy and manageable safety in advanced or metastatic PDAC in the second-line setting, representing a potential option in this patient population.
The p-MYH9/USP22/HIF-1α axis promotes lenvatinib resistance and cancer stemness in hepatocellular carcinoma
Authors: Shan Qiaonan , Yin Lu , Zhan Qifan , Yu Jiongjie , Pan Sheng , Zhuo Jianyong , Zhou Wei , Bao Jiaqi , Zhang Lincheng , Hong Jiachen , Xiang Jianan , Que Qingyang , Chen Kangchen , Xu Shengjun , Wang Jingrui , Zhu Yangbo , He Bin , Wu Jingbang , Xie Haiyang , Zheng Shusen , Feng Tingting , Ling Sunbin , Xu Xiao
Published: September 2024

Lenvatinib is a targeted drug used for first-line treatment of hepatocellular carcinoma (HCC). A deeper insight into the resistance mechanism of HCC against lenvatinib is urgently needed. In this study, we aimed to dissect the underlying mechanism of lenvatinib resistance (LR) and provide effective treatment strategies. We established an HCC model of acquired LR. Cell counting, migration, self-renewal ability, chemoresistance and expression of stemness genes were used to detect the stemness of HCC cells. Molecular and biochemical strategies such as RNA-sequencing, immunoprecipitation, mass spectrometry and ubiquitination assays were used to explore the underlying mechanisms. Patient-derived HCC models and HCC samples from patients were used to demonstrate clinical significance. We identified that increased cancer stemness driven by the hypoxia-inducible factor-1α (HIF-1α) pathway activation is responsible for acquired LR in HCC. Phosphorylated non-muscle myosin heavy chain 9 (MYH9) at Ser1943, p-MYH9 (Ser1943), could recruit ubiquitin-specific protease 22 (USP22) to deubiquitinate and stabilize HIF-1α in lenvatinib-resistant HCC. Clinically, p-MYH9 (Ser1943) expression was upregulated in HCC samples, which predicted poor prognosis and LR. A casein kinase-2 (CK2) inhibitor and a USP22 inhibitor effectively reversed LR in vivo and in vitro. Therefore, the p-MYH9 (Ser1943)/USP22/HIF-1α axis is critical for LR and cancer stemness. For the diagnosis and treatment of LR in HCC, p-MYH9 (Ser1943), USP22, and HIF-1α might be valuable as novel biomarkers and targets.
Current topic of vascular function in hypertension in 2023–2024
Authors: Maruhashi Tatsuya , Higashi Yukihito
Published: September 2024

Noninvasive tests of vascular function are useful for assessing the severity of atherosclerosis and risk of cardiovascular events, understanding the pathophysiology of cardiometabolic disorders, and investigating the effects of therapeutic interventions on cardiovascular morbidity and mortality, all of which can provide additional information for the management of patients with cardiovascular risk factors or a history of cardiovascular disease. In 2023–2024, many excellent articles on vascular function were published in Hypertension Research and other major cardiovascular and hypertension journals, and we summarize the emerging evidence on vascular function in this review. We hope that this review will be helpful for the management of patients with cardiovascular risk factors in clinical practice and for future basic and clinical research on vascular function.
A human Tau expressing zebrafish model of progressive supranuclear palsy identifies Brd4 as a regulator of microglial synaptic elimination
Authors: Bai Qing , Shao Enhua , Ma Denglei , Jiao Binxuan , Scheetz Seth D. , Hartnett-Scott Karen A. , Ilin Vladimir A. , Aizenman Elias , Kofler Julia , Burton Edward A.
Published: September 2024

Progressive supranuclear palsy (PSP) is an incurable neurodegenerative disease characterized by 4-repeat (0N/4R)-Tau protein accumulation in CNS neurons. We generated transgenic zebrafish expressing human 0N/4R-Tau to investigate PSP pathophysiology. Tau zebrafish replicated multiple features of PSP, including: decreased survival; hypokinesia; impaired optokinetic responses; neurodegeneration; neuroinflammation; synapse loss; and Tau hyperphosphorylation, misfolding, mislocalization, insolubility, truncation, and oligomerization. Using automated assays, we screened 147 small molecules for activity in rescuing neurological deficits in Tau zebrafish. (+)JQ1, a bromodomain inhibitor, improved hypokinesia, survival, microgliosis, and brain synapse elimination. A heterozygous brd4+/− mutant reducing expression of the bromodomain protein Brd4 similarly rescued these phenotypes. Microglial phagocytosis of synaptic material was decreased by (+)JQ1 in both Tau zebrafish and rat primary cortical cultures. Microglia in human PSP brains expressed Brd4. Our findings implicate Brd4 as a regulator of microglial synaptic elimination in tauopathy and provide an unbiased approach for identifying mechanisms and therapeutic targets in PSP.
Shared neutrophil and T cell dysfunction is accompanied by a distinct interferon signature during severe febrile illnesses in children
Authors: Patel Harsita , Carter Michael J. , Jackson Heather , Powell Oliver , Fish Matthew , Terranova-Barberio Manuela , Spada Filomena , Petrov Nedyalko , Wellman Paul , Darnell Sarah , Mustafa Sobia , Todd Katrina , Bishop Cynthia , Cohen Jonathan M. , Kenny Julia , van den Berg Sarah , Sun Thomas , Davis Francesca , Jennings Aislinn , Timms Emma , Thomas Jessica , Nyirendra Maggie , Nichols Samuel , Estamiana Elorieta Leire , D’Souza Giselle , Wright Victoria , De Tisham , Habgood-Coote Dominic , Ramnarayan Padmanabhan , Tissières Pierre , Whittaker Elizabeth , Herberg Jethro , Cunnington Aubrey , Kaforou Myrsini , Ellis Richard , Malim Michael H. , Tibby Shane M. , Shankar-Hari Manu , Levin Michael ,   On behalf of the DIAMONDS Consortium, van den Berg Sarah , Estamiana Elorieta Leire
Published: September 2024

Severe febrile illnesses in children encompass life-threatening organ dysfunction caused by diverse pathogens and other severe inflammatory syndromes. A comparative approach to these illnesses may identify shared and distinct features of host immune dysfunction amenable to immunomodulation. Here, using immunophenotyping with mass cytometry and cell stimulation experiments, we illustrate trajectories of immune dysfunction in 74 children with multi-system inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2, 30 with bacterial infection, 16 with viral infection, 8 with Kawasaki disease, and 42 controls. We explore these findings in a secondary cohort of 500 children with these illnesses and 134 controls. We show that neutrophil activation and apoptosis are prominent in multi-system inflammatory syndrome, and that this is partially shared with bacterial infection. We show that memory T cells from patients with multi-system inflammatory syndrome and bacterial infection are exhausted. In contrast, we show viral infection to be characterized by a distinct signature of decreased interferon signaling and lower interferon receptor gene expression. Improved understanding of immune dysfunction may improve approaches to immunomodulator therapy in severe febrile illnesses in children.
Intergenerational effects of a casino-funded family transfer program on educational outcomes in an American Indian community
Authors: Bruckner Tim A. , Bustos Brenda , Dodge Kenneth A. , Lansford Jennifer E. , Odgers Candice L. , Copeland William E.
Published: September 2024

Cash transfer policies have been widely discussed as mechanisms to curb intergenerational transmission of socioeconomic disadvantage. In this paper, we take advantage of a large casino-funded family transfer program introduced in a Southeastern American Indian Tribe to generate difference-in-difference estimates of the link between children’s cash transfer exposure and third grade math and reading test scores of their offspring. Here we show greater math (0.25 standard deviation [SD], p =.0148, 95% Confidence Interval [CI]: 0.05, 0.45) and reading (0.28 SD, p = .0066, 95% CI: 0.08, 0.49) scores among American Indian students whose mother was exposed ten years longer than other American Indian students to the cash transfer during her childhood (or relative to the non-American Indian student referent group). Exploratory analyses find that a mother’s decision to pursue higher education and delay fertility appears to explain some, but not all, of the relation between cash transfers and children’s test scores. In this rural population, large cash transfers have the potential to reduce intergenerational cycles of poverty-related educational outcomes.
Claustrum and dorsal endopiriform cortex complex cell-identity is determined by Nurr1 and regulates hallucinogenic-like states in mice
Authors: Mantas Ioannis , Flais Ivana , Masarapu Yuvarani , Ionescu Tudor , Frapard Solène , Jung Felix , Le Merre Pierre , Saarinen Marcus , Tiklova Katarina , Salmani Behzad Yaghmaeian , Gillberg Linda , Zhang Xiaoqun , Chergui Karima , Carlén Marie , Giacomello Stefania , Hengerer Bastian , Perlmann Thomas , Svenningsson Per
Published: September 2024

The Claustrum/dorsal endopiriform cortex complex (CLA) is an enigmatic brain region with extensive glutamatergic projections to multiple cortical areas. The transcription factor Nurr1 is highly expressed in the CLA, but its role in this region is not understood. By using conditional gene-targeted mice, we show that Nurr1 is a crucial regulator of CLA neuron identity. Although CLA neurons remain intact in the absence of Nurr1, the distinctive gene expression pattern in the CLA is abolished. CLA has been hypothesized to control hallucinations, but little is known of how the CLA responds to hallucinogens. After the deletion of Nurr1 in the CLA, both hallucinogen receptor expression and signaling are lost. Furthermore, functional ultrasound and Neuropixel electrophysiological recordings revealed that the hallucinogenic-receptor agonists’ effects on functional connectivity between prefrontal and sensorimotor cortices are altered in Nurr1-ablated mice. Our findings suggest that Nurr1-targeted strategies provide additional avenues for functional studies of the CLA.
High radiative forcing climate scenario relevance analyzed with a ten-million-member ensemble
Authors: Sarofim Marcus C. , Smith Christopher J. , Malek Parker , McDuffie Erin E. , Hartin Corinne A. , Lay Claire R. , McGrath Sarah
Published: September 2024

Developing future climate projections begins with choosing future emissions scenarios. While scenarios are often based on storylines, here instead we produce a probabilistic multi-million-member ensemble of radiative forcing trajectories to assess the relevance of future forcing thresholds. We coupled a probabilistic database of future greenhouse gas emission scenarios with a probabilistically calibrated reduced complexity climate model. In 2100, we project median forcings of 5.1 watt per square meters (5th to 95th percentiles of 3.3 to 7.1), with roughly 0.5% probability of exceeding 8.5 watt per square meters, and a 1% probability of being lower than 2.6 watt per square meters. Although the probability of 8.5 watt per square meters scenarios is low, our results support their continued utility for calibrating damage functions, characterizing climate in the 22nd century (the probability of exceeding 8.5 watt per square meters increases to about 7% by 2150), and assessing low-probability/high-impact futures.
Mosquito salivary apyrase regulates blood meal hemostasis and facilitates malaria parasite transmission
Authors: Pala Zarna Rajeshkumar , Alves e Silva Thiago Luiz , Minai Mahnaz , Crews Benjamin , Patino-Martinez Eduardo , Carmona-Rivera Carmelo , Valenzuela Leon Paola Carolina , Martin-Martin Ines , Flores-Garcia Yevel , Cachau Raul E. , Muslinkina Liya , Gittis Apostolos G. , Srivastava Naman , Garboczi David N. , Alves Derron A. , Kaplan Mariana J. , Fischer Elizabeth , Calvo Eric , Vega-Rodriguez Joel
Published: September 2024

The evolution of hematophagy involves a series of adaptations that allow blood-feeding insects to access and consume blood efficiently while managing and circumventing the host’s hemostatic and immune responses. Mosquito, and other insects, utilize salivary proteins to regulate these responses at the bite site during and after blood feeding. We investigated the function of Anopheles gambiae salivary apyrase (AgApyrase) in regulating hemostasis in the mosquito blood meal and in Plasmodium transmission. Our results demonstrate that salivary apyrase, a known inhibitor of platelet aggregation, interacts with and activates tissue plasminogen activator, facilitating the conversion of plasminogen to plasmin, a human protease that degrades fibrin and facilitates Plasmodium transmission. We show that mosquitoes ingest a substantial amount of apyrase during blood feeding, which reduces coagulation in the blood meal by enhancing fibrin degradation and inhibiting platelet aggregation. AgApyrase significantly enhanced Plasmodium infection in the mosquito midgut, whereas AgApyrase immunization inhibited Plasmodium mosquito infection and sporozoite transmission. This study highlights a pivotal role for mosquito salivary apyrase for regulation of hemostasis in the mosquito blood meal and for Plasmodium transmission to mosquitoes and to the mammalian host, underscoring the potential for strategies to prevent malaria transmission.
Theoretical approaches for the description of plasmon generated hot carriers phenomena
Authors: Vanzan Mirko , Marsili Margherita
Published: September 2024

Plasmonic-driven photocatalysis is one of the most vibrant and promising field in nanoscience. Out of the various mechanisms known to activate chemical reactions in molecules interacting with optically excited nanostructures, the one involving production and transfer of Hot Carriers (HCs) is among the most relevant. Over the past decade, along with stunning advances on HCs control and manipulation, a variety of theoretical and computational strategies have been developed to model this phenomenon and explore its underlying physics. These techniques have provided comprehensive understandings of HCs life stages and dynamics, and allowed valuable insights on their role in photocatalysis. However, to date it is hard to extricate within the plethora of methods developed and the growing number of applications they found. The purpose of this review is to survey the approaches employed so far to model HCs photophysics, rationalizing and classifying the different studies in terms of modelization, theoretical approaches, and approximations.
MEPO-ML: a robust graph attention network model for rapid generation of partial atomic charges in metal-organic frameworks
Authors: Luo Jun , Said Omar Ben , Xie Peigen , Gibaldi Marco , Burner Jake , Pereira Cécile , Woo Tom K.
Published: September 2024

Accurate computation of the gas adsorption properties of MOFs is usually bottlenecked by the DFT calculations required to generate partial atomic charges. Therefore, large virtual screenings of MOFs often use the QEq method which is rapid, but of limited accuracy. Recently, machine learning (ML) models have been trained to generate charges in much better agreement with DFT-derived charges compared to the QEq models. Previous ML charge models for MOFs have all used training sets with less than 3000 MOFs obtained from the CoRE MOF database, which has recently been shown to have high structural error rates. In this work, we developed a graph attention network model for predicting DFT-derived charges in MOFs where the model was developed with the ARC-MOF database that contains 279,632 MOFs and over 40 million charges. This model, which we call MEPO-ML, predicts charges with a mean absolute error of 0.025e on our test set of over 27 K MOFs. Other ML models reported in the literature were also trained using the same dataset and descriptors, and MEPO-ML was shown to give the lowest errors. The gas adsorption properties evaluated using MEPO-ML charges are found to be in significantly better agreement with the reference DFT-derived charges compared to the empirical charges, for both polar and non-polar gases. Using only a single CPU core on our benchmark computer, MEPO-ML charges can be generated in less than two seconds on average (including all computations required to apply the model) for MOFs in the test set of 27 K MOFs.
Recent advances and challenges in single cell protein (SCP) technologies for food and feed production
Authors: Li Yu Pin , Ahmadi Fatemeh , Kariman Khalil , Lackner Maximilian
Published: September 2024

The global population is increasing, with a predicted demand for 1250 million tonnes of animal-derived protein by 2050, which will be difficult to meet. Single-cell protein (SCP) offers a sustainable solution. This review covers SCP production mechanisms, microbial and substrate choices, and advancements in metabolic engineering and CRISPR-Cas. It emphasizes second-generation substrates and fermentation for a circular economy. Despite challenges like high nucleic acid content, SCP promises to solve the global nutrition problem.
9,000 years of genetic continuity in southernmost Africa demonstrated at Oakhurst rockshelter
Authors: Gretzinger Joscha , Gibbon Victoria E. , Penske Sandra E. , Sealy Judith C. , Rohrlach Adam B. , Salazar-García Domingo C. , Krause Johannes , Schiffels Stephan
Published: September 2024

Southern Africa has one of the longest records of fossil hominins and harbours the largest human genetic diversity in the world. Yet, despite its relevance for human origins and spread around the globe, the formation and processes of its gene pool in the past are still largely unknown. Here, we present a time transect of genome-wide sequences from nine individuals recovered from a single site in South Africa, Oakhurst Rockshelter. Spanning the whole Holocene, the ancient DNA of these individuals allows us to reconstruct the demographic trajectories of the indigenous San population and their ancestors during the last 10,000 years. We show that, in contrast to most regions around the world, the population history of southernmost Africa was not characterized by several waves of migration, replacement and admixture but by long-lasting genetic continuity from the early Holocene to the end of the Later Stone Age. Although the advent of pastoralism and farming substantially transformed the gene pool in most parts of southern Africa after 1,300 bp, we demonstrate using allele-frequency and identity-by-descent segment-based methods that the ‡Khomani San and Karretjiemense from South Africa still show direct signs of relatedness to the Oakhurst hunter-gatherers, a pattern obscured by recent, extensive non-Southern African admixture. Yet, some southern San in South Africa still preserve this ancient, Pleistocene-derived genetic signature, extending the period of genetic continuity until today.
High-throughput drug screening identifies novel therapeutics for Low Grade Serous Ovarian Carcinoma
Authors: Pishas Kathleen I. , Cowley Karla J. , Llaurado-Fernandez Marta , Kim Hannah , Luu Jennii , Vary Robert , Bowden Nikola A. , Campbell Ian G. , Carey Mark S. , Simpson Kaylene J. , Cheasley Dane
Published: September 2024

Low grade serous carcinoma (LGSOC) is a rare epithelial ovarian cancer with unique molecular characteristics compared to the more common tubo-ovarian high-grade serous ovarian carcinoma. Pivotal clinical trials guiding the management of epithelial ovarian cancer lack sufficient cases of LGSOC for meaningful subgroup analysis, hence overall findings cannot be extrapolated to rarer chemo-resistant subtypes such as LGSOC. Furthermore, there is a need for more effective therapies for the treatment of relapsed disease, as treatment options are limited. To address this, we conducted the largest quantitative high-throughput drug screening effort (n = 3436 compounds) in 12 patient-derived LGSOC cell lines and one normal ovary cell line to identify unexplored therapeutic avenues. Using a combination of high-throughput robotics, high-content imaging and novel data analysis pipelines, our data set identified 60 high and 19 moderate confidence hits which induced cancer cell specific cytotoxicity at the lowest compound dose assessed (0.1 µM). We also revealed a series of known (mTOR/PI3K/AKT) and novel (EGFR and MDM2-p53) drug classes in which LGSOC cell lines showed demonstrable susceptibility to.
UPLC-PDA factorial design assisted method for simultaneous determination of oseltamivir, dexamethasone, and remdesivir in human plasma
Authors: EL-Shorbagy Hanan I. , Mohamed Mona A. , El-Gindy Alaa , Hadad Ghada M. , Belal Fathalla
Published: September 2024

A green and simple UPLC method was developed and optimized, adopting a factorial design for simultaneous determination of oseltamivir phosphate and remdesivir with dexamethasone as a co-administered drug in human plasma and using daclatasvir dihydrochloride as an internal standard within 5 min. The separation was established on UPLC column BEH C18 1.7 μm (2.1 $$\times $$
×
100.0 mm) connected to UPLC pre-column BEH 1.7 μm (2.1 $$\times $$
×
5.0 mm) at 50 °C with an injection volume of 10 μL. The photodiode array detector (PDA) was set at three wavelengths of 220, 315, and 245 nm for oseltamivir phosphate, the internal standard, and both dexamethasone and remdesivir, respectively. The mobile phase consisted of methanol and ammonium acetate solution (40 mM) adjusted to pH 4 in a ratio of 61.5:38.5 (v/v) with a flow rate of 0.25 mL min−1. The calibration curves were linear over 500.0–5000.0 ng mL−1 for oseltamivir phosphate, over 10.0–500.0 ng mL−1 and 500.0–5000.0 ng mL−1 for dexamethasone, and over 20.0–500 ng mL−1 and 500.0–5000.0 ng mL−1 for remdesivir. The Gibbs free energy and Van't Hoff plots were used to investigate the effect of column oven temperatures on retention times. Fluoride-EDTA anticoagulant showed inhibition activity on the esterase enzyme in plasma. The proposed method was validated according to the M10 ICH, FDA, and EMA’s bioanalytical guidelines. According to Eco-score, GAPI, and AGREE criteria, the proposed method was considered acceptable green.
Green synthesis of silver and gold-doped zinc oxide nanocomposite with propolis extract for enhanced anticancer activity
Authors: Abdelsattar Abdallah S. , Yakoup Aghapy Yermans , Kamel Azza G. , El-Shibiny Ayman
Published: September 2024

Metal and metal oxide nanocomposites have unique properties and are promising for antibacterial and anticancer applications. In this work, we aimed to highlight the relationship between the biosynthesis ways of silver and gold-doped zinc oxide nanocomposites and their functions as anticancer on cell lines (MCF-7 and HepG2). The propolis was used to biosynthesize four different nanoparticles with the same components, including zinc, gold and silver. The nanocomposites were characterized using various techniques, including ultraviolet–visible spectroscopy (UV–Vis), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Energy Dispersive X-ray analysis (EDX) and cytotoxicity assays. The result of this study showed that formed nanocomposites have a similar level of Zn, Au, and Ag, ranging from 23–34%, 2–6%, and 2–3%, respectively. In addition, adding the components simultaneously produces the fastest color change, and the fabricated nanoparticles have spherical shapes with different layers. In addition, the prepared nanoparticles influenced the cell viability of the cancer cell lines, with the most effective one when Zn, Au, and Ag were added spontaneously to form a nanocomposite called (All) with IC50 of 24.5 µg/mL for MCF7 cells and 29.1 µg/mL for HepG2 cells. Thus, the study illustrates that the preparation of nanocomposite generated through green synthesis with different methods significantly affects the structure and function and may improve the synthesis of nanocomposite to be developed into an efficacious therapeutic agent for cancers. In addition, this study opens the door toward a novel track in the field of nanocomposites as it links the synthesis with structure and function. Further anti-cancer properties, as well as animal testing are needed for those nanocomposites.
National Park visitors perceive benefits for themselves and wildlife under blended red-white outdoor lighting
Authors: Fristrup Kurt , Miller Zachary D. , Newton Jennifer , Buckley Stephanie , Cole Hunter , Linares Carlos , Donners Maurice , Taff B. Derrick , Beeco J. Adam , Barber Jesse , Newman Peter
Published: September 2024

Visitors to Colter Bay Village in Grand Teton National Park were surveyed to elicit their evaluations of experimental outdoor lighting conditions. Luminaires capable of dimming and switching between two LED modules (white, blended red-white) were installed in street and parking areas. The blended red-white lamps consisted of 30 narrowband LED with a peak wavelength 623 nm and two 3000 K white LEDs. Similar “red” lamps were previously shown to reduce impacts to bats and insects. The white and red lamps were closely matched for luminance. Measured horizontal illuminance at survey locations had an interquartile range from 0.63 to 3.82 lx. The red lamps produced lower perceived brightness (VB2(λ)), even after reflection off asphalt, yet survey participants expressed higher ratings for visual comfort and safety under red lighting. Surveys conducted earlier in the evening, with higher levels of predicted solar and measured horizontal illuminance, rated higher on visual comfort and safety, though these correlations were not as strong as the effect of lamp color. Streetlight ratings and support for lighting that protected natural resources were not contingent upon age or gender. Survey participants assessed red lighting as more protective of the environment. These results demonstrate that outdoor lighting designed to reduce ecological impacts can yield superior nocturnal experience for pedestrians.
Hybrid quantum-classical computation for automatic guided vehicles scheduling
Authors: Śmierzchalski Tomasz , Pawłowski Jakub , Przybysz Artur , Pawela Łukasz , Puchała Zbigniew , Koniorczyk Mátyás , Gardas Bartłomiej , Deffner Sebastian , Domino Krzysztof
Published: September 2024

Motivated by recent efforts to develop quantum computing for practical, industrial-scale challenges, we demonstrate the effectiveness of state-of-the-art hybrid (not necessarily quantum) solvers in addressing the business-centric optimization problem of scheduling Automatic Guided Vehicles (AGVs). Some solvers can already leverage noisy intermediate-scale quantum (NISQ) devices. In our study, we utilize D-Wave hybrid solvers that implement classical heuristics with potential assistance from a quantum processing unit. This hybrid methodology performs comparably to existing classical solvers. However, due to the proprietary nature of the software, the precise contribution of quantum computation remains unclear. Our analysis focuses on a practical, business-oriented scenario: scheduling AGVs within a factory constrained by limited space, simulating a realistic production setting. Our approach maps a realistic AGVs problem onto one reminiscent of railway scheduling and demonstrates that the AGVs problem is better suited to quantum computing than its railway counterpart, the latter being denser in terms of the average number of constraints per variable. The main idea here is to highlight the potential usefulness of a hybrid approach for handling AGVs scheduling problems of practical sizes. We show that a scenario involving up to 21 AGVs, significant due to possible deadlocks, can be efficiently addressed by a hybrid solver in seconds.
Machine learning misclassification networks reveal a citation advantage of interdisciplinary publications only in high-impact journals
Authors: Lyutov Alexey , Uygun Yilmaz , Hütt Marc-Thorsten
Published: September 2024

Given a large enough volume of data and precise, meaningful categories, training a statistical model to solve a classification problem is straightforward and has become a standard application of machine learning (ML). If the categories are not precise, but rather fuzzy, as in the case of scientific disciplines, the systematic failures of ML classification can be informative about properties of the underlying categories. Here we classify a large volume of academic publications using only the abstract as information. From the publications that are classified differently by journal categories and ML categories (i.e., misclassified publications, when using the journal assignment as ground truth) we construct a network among disciplines. Analysis of these misclassifications provides insight in two topics at the core of the science of science: (1) Mapping out the interplay of disciplines. We show that this misclassification network is informative about the interplay of academic disciplines and it is similar to, but distinct from, a citation-based map of science, where nodes are scientific disciplines and an edge indicates a strong co-citation count between publications in these disciplines. (2) Analyzing the success of interdisciplinarity. By evaluating the citation patterns of publications, we show that misclassification can be linked to interdisciplinarity and, furthermore, that misclassified articles have different citation frequencies than correctly classified articles: In the highest 10 percent of journals in each discipline, these misclassified articles are on average cited more frequently, while in the rest of the journals they are cited less frequently.
Fisheries shocks provide an opportunity to reveal multiple recruitment sources of sardine in the Sea of Japan
Authors: Sakamoto Tatsuya , Takahashi Motomitsu , Shirai Kotaro , Aono Tomoya , Ishimura Toyoho
Published: September 2024

The abrupt decline in sardine catches in the Sea of Japan and the East China Sea (SJ-ECS) in 2014 and 2019 and the recovery in the following years call into question the current assumption that sardines in the SJ-ECS form a self-recruiting subpopulation. To test this hypothesis, we analysed otolith stable oxygen and carbon isotope profiles (δ18O, δ13C) of age-0 and age-1 sardines from 2010 and 2013–2015 year-classes captured in the SJ-ECS, as geographic markers for nursery areas. Age-0 sardines generally showed a significant ontogenetic decrease in otolith δ18O from larval to juvenile stages. However, the majority of age-1 captured in spring 2011, 2015 and 2016 showed non-decreasing otolith δ18O profiles, suggesting that the age-0 off the Japanese coast were not the main source of recruitment. Different migration groups were thus indicated: the “locals” growing up off the Japanese coast and the migrating “nonlocals”. The isotope profiles of the “nonlocals” overlapped with those of age-0 captured in the subarctic North Pacific, suggesting that they may be migrants from the Pacific, or perhaps an unobserved northward migration group in the SJ-ECS. Our results highlight the considerable uncertainty in the population structure assumed in current stock assessment models for Japanese sardine.
Effect of silver nanoparticles foliar application on the nutritional properties of potato tubers
Authors: Tokarz Krzysztof M. , Mazur Tomasz , Hanula Monika , Makowski Wojciech , Zawal Piotr , Jędrzejczyk Roman J. , Szacilowski Konrad , Mazur Stanisław , Wesołowski Wojciech , Tokarz Barbara
Published: September 2024

The aim of presented study was to test nutritional properties of potato tubers and silver ions accumulation pattern after foliar application of silver nanoparticles (AgNPs) during potato vegetation. Potato plants were sprayed with different concentration of Ag nanoparticles (0.1, 1.0 and 10 mg·dm−3) synthesized with incorporation with sodium dodecyl sulphate (SDS) and sodium citrate as stabilizing agent. The lowest amounts of silver ions were transported to the tubers after spraying with AgNPs synthesized with SDS, rather than with citrate. Nevertheless silver ions accumulation in tubers was negligible. SDS method of synthesis was more favourable in terms of nutritional properties of potato tubers. The highest tested concentration of AgNPs_SDS had a favourable effect on a variety of macro- and micronutrients, ascorbic acid and soluble sugars. In turn, lower concentrations of AgNPs_SDS increased the content of phenolic compounds and free radical scavenging efficiency of tubers. These correlations were also confirmed by Principal Component Analysis.
Emergence of group size disparity in growing networks with adoption
Authors: Sun Jun , Karimi Fariba
Published: September 2024

Social and technical networks undergo constant evolution driven by both existing entities and newcomers. In academia, research papers are continually cited by new papers, while senior researchers integrate newly arrived junior researchers into their academic networks. Moreover, social systems can be influenced by external factors that could indirectly impact their growth patterns. For instance, systematic discrimination against certain groups in academia or managerial positions can impede their long-term growth, especially when combined with group-level preferences in hiring or adoption, as observed in our study. To address this, we introduce a network growth and adoption model where generalised preferential attachment and asymmetric mixing act as the two fundamental mechanisms of growth and adoption. We show analytically and numerically that these mechanisms can recover the empirical properties of citation and collaboration growth, as well as the inequalities observed in the growth dynamics of groups. This model can be used to investigate the effect of intervention in group mixing preferences to overcome the cumulative disparities in the group-level dynamics.
A population-based study of familial coaggregation and shared genetic etiology of psychiatric and gastrointestinal disorders
Authors: Pan Yi-Jiun , Lin Mei-Chen , Liou Jyh-Ming , Fan Chun-Chieh , Su Mei-Hsin , Chen Cheng-Yun , Wu Chi-Shin , Chen Pei-Chun , Huang Yen-Tsung , Wang Shi-Heng
Published: September 2024

Background

It has been proposed that having a psychiatric disorder could increase the risk of developing a gastrointestinal disorder, and vice versa. The role of familial coaggregation and shared genetic loading between psychiatric and gastrointestinal disorders remains unclear.

Methods

This study used the Taiwan National Health Insurance Research Database; 4,504,612 individuals born 1970–1999 with parental information, 51,664 same-sex twins, and 3,322,959 persons with full-sibling(s) were enrolled. Genotyping was available for 106,796 unrelated participants from the Taiwan Biobank. A logistic regression model was used to examine the associations of individual history, affected relatives, and polygenic risk scores (PRS) for schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD), with the risk of peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD), and vice versa.

Results

Here we show that parental psychiatric disorders are associated with gastrointestinal disorders. Full-siblings of psychiatric cases have an increased risk of gastrointestinal disorders except for SCZ/BPD and IBD; the magnitude of coaggregation is higher in same-sex twins than in full-siblings. The results of bidirectional analyses mostly remain unchanged. PRS for SCZ, MDD, and OCD are associated with IBS, PUD/GERD/IBS/IBD, and PUD/GERD/IBS, respectively. PRS for PUD, GERD, IBS, and IBD are associated with MDD, BPD/MDD, SCZ/BPD/MDD, and BPD, respectively.

Conclusions

There is familial coaggregation and shared genetic etiology between psychiatric and gastrointestinal comorbidity. Individuals with psychiatric disorder-affected relatives or with higher genetic risk for psychiatric disorders should be monitored for gastrointestinal disorders, and vice versa.
Acetylation of TIR domains in the TLR4-Mal-MyD88 complex regulates immune responses in sepsis
Authors: Li Xue , Li Xiangrong , Huang Pengpeng , Zhang Facai , Du Juanjuan K , Kong Ying , Shao Ziqiang , Wu Xinxing , Fan Weijiao , Tao Houquan , Zhou Chuanzan , Shao Yan , Jin Yanling , Ye Meihua , Chen Yan , Deng Jong , Shao Jimin , Yue Jicheng , Cheng Xiaju , Chinn Y Eugene
Published: September 2024

Activation of the Toll-like receptor 4 (TLR4) by bacterial endotoxins in macrophages plays a crucial role in the pathogenesis of sepsis. However, the mechanism underlying TLR4 activation in macrophages is still not fully understood. Here, we reveal that upon lipopolysaccharide (LPS) stimulation, lysine acetyltransferase CBP is recruited to the TLR4 signalosome complex leading to increased acetylation of the TIR domains of the TLR4 signalosome. Acetylation of the TLR4 signalosome TIR domains significantly enhances signaling activation via NF-κB rather than IRF3 pathways. Induction of NF-κB signaling is responsible for gene expression changes leading to M1 macrophage polarization. In sepsis patients, significantly elevated TLR4-TIR acetylation is observed in CD16+ monocytes combined with elevated expression of M1 macrophage markers. Pharmacological inhibition of HDAC1, which deacetylates the TIR domains, or CBP play opposite roles in sepsis. Our findings highlight the important role of TLR4-TIR domain acetylation in the regulation of the immune responses in sepsis, and we propose this reversible acetylation of TLR4 signalosomes as a potential therapeutic target for M1 macrophages during the progression of sepsis.
A shorter splicing isoform antagonizes ZBP1 to modulate cell death and inflammatory responses
Authors: Nagata Masahiro , Carvalho Schäfer Yasmin , Wachsmuth Laurens , Pasparakis Manolis
Published: September 2024

Z-DNA-binding protein 1 (ZBP1) is an interferon-inducible sensor of Z-DNA and Z-RNA, which has emerged as a critical regulator of cell death and inflammation. ZBP1 binds Z-DNA and Z-RNA via its Zα domains, and signals by engaging RIPK3 and RIPK1 via its RIP homotypic interaction motifs (RHIMs). Here, we show that mice express an alternatively-spliced shorter ZBP1 isoform (ZBP1-S), which harbours the Zα domains but lacks the RHIMs, and acts as an endogenous inhibitor of the full-length protein (ZBP1-L). Mice and cells expressing only ZBP1-S are resistant to ZBP1-mediated cell death and inflammation. In contrast, cells lacking ZBP1-S show increased ZBP1-L-induced death compared to cells expressing both isoforms. Moreover, loss of the short isoform accelerates and exacerbates skin inflammation induced by ZBP1-mediated necroptosis of RIPK1-deficient keratinocytes, revealing an important physiological role of ZBP1-S. Mechanistically, ZBP1-S suppresses ZBP1-L-mediated cell death by binding to Z-nucleic acids via its Zα domains. Therefore, ZBP1-S acts as an endogenous inhibitor that competes with full-length ZBP1-L for binding Z-nucleic acid ligands to fine-tune ZBP1-mediated cell death and inflammation.
MADAS: a Python framework for assessing similarity in materials-science data
Authors: Kuban Martin , Rigamonti Santiago , Draxl Claudia
Published: September 2024

MADAS is a computational framework that supports all steps of similarity analysis, including the collection and storage of data, the development and computation of fingerprints, metrics to measure similarity, and data analytics and machine learning.
Platinum(ii) bis(arylacetylide) complexes bearing diarylamino-substituted bipyridine ligands for solution-processable phosphorescent OLED applications
Authors: Wong Wai-Yeung , Xie Zheng , Wang Qiwei , Jiang Lu , Li Junlong , Zhang Baohua , Yi Xiuyu , Xie Zhiyuan , Zhao Jianzhang
Published: September 2024

New platinum(ii) bis(arylacetylide) complexes with diarylamino-substituted bipyridine ligands are reported. These butterfly-shaped metallophosphors with improved hole-transporting traitsare good emitters for solution-processed phosphorescent OLEDs.
Recyclable ionic iron-substituted ceria: a precious metal-free, ligand-free, and versatile catalyst for C–C coupling and ipso-hydroxylation of arylboronic acid
Authors: Prasanna
Published: September 2024

A recyclable precious metal-free Ce0.95Fe0.05O2-δ catalyst was synthesized by solution combustion method for selective conversion of various arylboronic acids to corresponding biphenyls and phenols employing K2S2O8 and H2O2 respectively.
Phosphorus release from sewage sludge and digestate driven by biological sulfate reduction: effect of feed sulfate concentration and thermal hydrolysis
Authors: Di Capua Francesco , Papirio Stefano , Matassa Silvio , Pirozzi Francesco , Esposito Giovanni
Published: September 2024

Recovering phosphorus from sewage sludge is a strategic, circular approach to ensure long-term phosphorus availability for future generations, supporting sustainability and resource preservation.
Association of unsweetened and sweetened cereal consumption with all-cause and cause-specific mortality: a large prospective population-based cohort study
Authors: Zhang Lei , Ma Chunhui , Huang Hao , Li Dapeng , Zhang Ding , Wu Tianqi , Chu Minjie , Hu Fulan
Published: September 2024

Association of unsweetened and sweetened cereals consumption with all-cause and cause-specific mortality: a large prospective population-based cohort study.
Advancing sustainability: a novel biopolymer-based degradable nanoclay composite film for next-generation packaging
Authors: Tabassum Zeba , Girdhar Madhuri , Malik Tabarak , Kumar Anil , Mohan Anand
Published: September 2024

Global concerns are increasing worldwide owing to the utilization of non-renewable fossil fuel-derived polymeric films for the packaging of perishables and other related commodities.
Slippery hydrogel surface on PTFE hollow fiber membranes for sustainable emulsion separation
Authors: Ding Yajie , Zhu Yue , Wang Jiawei , Wang Jianqiang , Liu Fu
Published: September 2024

Establishing an efficient and sustainable membrane module is of great significance for practical oil/water emulsion separation.
Synergistic effect of Zn-AgIn5S8/CdS Z-scheme heterojunction and S-doped rGO for efficient removal of chromium from contaminated water
Authors: Mishra Soumya , Sahoo Naresh Kumar , Sahoo Prasanta Kumar , Sahoo Satyanjib , Rout Prangya Ranjan , Rath Goutam
Published: September 2024

This study aimed to synthesize a Zn-AgIn5S8/CdS/SrGO nanocomposite for Cr(vi) removal from contaminated water under solar irradiation.
Correction: Fluorescence imaging of cellular GSH to reveal the hindering influence of rutin on ferroptosis
Authors: Mehmood Abdul Hadi , Chang Jia , Wang Yan , Li Shijing , Ma Jiale , Dong Baoli , Liu Hong
Published: September 2024

Correction for ‘Fluorescence imaging of cellular GSH to reveal the hindering influence of rutin on ferroptosis’ by Abdul Hadi Mehmood et al., New J. Chem., 2024, 48, 14175–14181, https://doi.org/10.1039/D4NJ00397G.
Prodrug nanotherapy demonstrates in vivo anticryptosporidial efficacy in a mouse model of chronic Cryptosporidium infection
Authors: Ranjan Amalendu P. , Czyzyk Daniel J. , Martinez-Traverso Griselle , Sadiqova Aygul , Valhondo Margarita , Schaefer Deborah A. , Spasov Krasimir A. , Jorgensen William L. , Vishwanatha Jamboor K. , Riggs Michael W. , Castellanos-Gonzalez Alejandro , Anderson Karen S.
Published: September 2024

Enteric-coated oral nanotherapy shows in vivo anticryptosporidial efficacy.
Zr6O8 core cluster with formula unit [Zr6O4(OH)4(OH2)8(CH3COO)4(SO4)4]·nH2O obtained under mild conditions
Authors: Garzón-Serrano Andrea Y. , Lozano Johan D. , Perez Leon D. , Sierra César A. , Macías Mario A.
Published: September 2024

Cluster with Zr6O8 core and formula unit [Zr6O4(OH)4(OH2)8(CH3COO)4(SO4)4]·nH2O was synthesized under mild conditions forming three-dimensional maze of tunnels.
Application of the three-reactor hydrogenation process in the recycling utilization of waste lubricating oil and study on the catalyst deactivation mechanism
Authors: Fang You , Zhang Peng , Guo Mengya , Guo Shuke , Wang Fujiang , Tang Mingxing
Published: September 2024

The three-reactor process removes Si and B from waste lubricating oil thereby mitigating the poisoning of the catalyst. This refinement doubles the service life of the catalysts relative to the conventional two-reactor process.