bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular and transcriptional basis of bidirectional CD4+ T cell exhaustion in oropharyngeal squamous cell carcinoma
Authors: Cheng Danni , Qiu Ke , Li Daibo , Mao Minzi , Rao Yufang , Song Yao , Feng Lan , Shao Xiuli , Jiang Chuanhuan , Wang Yan , Li Li , Chen Xuemei , Wu Sisi , Wang Haiyang , Liu Jun , Yu Haopeng , Zhang Wei , Chen Fei , Zhao Yu , Ren Jianjun 
Published: June 2024

AbstractTumor‐infiltrating CD4+ T cells orchestrate the adaptive immune response through remarkable plasticity, and the expression patterns of exhaustion‐related inhibitory receptors in these cells differ significantly from those of CD8+ T cells. Thus, a better understanding of the molecular basis of CD4+ T cell exhaustion and their responses to immune checkpoint blockade (ICB) is required. Here, we integrated multiomics approaches to define the phenotypic and molecular profiles of exhausted CD4+ T cells in oropharyngeal squamous cell carcinoma (OPSCC). Two distinct immune‐promoting (Module 1) and immunosuppressive (Module 2) functional modules in tumor‐infiltrating CD4+ T cells were identified, and both the immune‐promoting function of Module 1 cells and immunosuppressive function of Module 2 cells were positively associated with their corresponding exhaustion states. Furthermore, the application of ICBs targeting effector CD4+ T cells in Module 1 (αPD‐1) and Treg cells in Module 2 (αCTLA‐4) in mouse models could help reinvigorate the effector function of Module 1‐exhausted CD4+ T cells and reduce the immunosuppressive function of Module 2‐exhausted CD4+ T cells, ultimately promoting OPSCC tumor regression. Taken together, our study provides a crucial cellular basis for the selection of optimal ICB in treating OPSCC.
Hyperglycemia Inhibits Hepatic SHBG Synthesis Through the NGBR‐AMPK‐HNF4 Pathway in Rats with Polycystic Ovary Syndrome Induced by Letrozole in Combination with a High‐Fat Diet
Authors: Hu Rao , Long Shuanglian , Luo Min , Tang Bowen , Tan Tao , Dong Weilei , Wang Qian , Zhang Jiaming 
Published: June 2024

ScopePolycystic ovary syndrome (PCOS) is closely related to non‐alcoholic fatty liver disease (NAFLD), and sex hormone‐binding globulin (SHBG) is a glycoprotein produced by the liver. Hepatic lipogenesis inhibits hepatic SHBG synthesis, which leads to hyperandrogenemia and ovarian dysfunction in PCOS. Therefore, this study aims to characterize the mechanism whereby liver lipogenesis inhibits SHBG synthesis.Methods and resultsThis study establishes a rat model of PCOS complicated by NAFLD using a high‐fat diet in combination with letrozole and performs transcriptomic analysis of the liver. Transcriptomic analysis of the liver shows that the expression of neurite growth inhibitor‐B receptor (NgBR), hepatocyte nuclear factor 4α (HNF4α), and SHBG is low. Meantime, HepG2 cells are treated with palmitic acid (PA) to model NAFLD in vitro, which causes decreases in the expression of NgBR, HNF4α, and SHBG. However, the expression of HNF4α and SHBG is restored by treatment with the AMP‐activated protein kinase (AMPK) agonist AICAR.ConclusionsNgBR regulates the expression of HNF4α by activating the AMPK signaling pathway, thereby affecting the synthesis of SHBG in the liver. Further mechanistic studies regarding the effect of liver fat on NGBR expression are warranted.
Determination of Veratrum alkaloid contents in three Veratrum species by HPLC‐MS/MS
Authors: Siegle Julia , Pietsch Jörg 
Published: June 2024

AbstractIntroductionVeratrum alkaloids have gained attention due to their toxic effects and potential pharmaceutical applications, particularly in cancer and cardiology. Over 200 alkaloids are found in species of the Veratrum genus. The alkaloid composition and concentrations can greatly vary in plants depending on factors like species, plant part, location, season, weather, or nutrients.ObjectiveThis study aims an analytical approach to analyze and quantify Veratrum alkaloids in different plant parts of Veratrum species. The purpose is to contribute essential alkaloid concentration data for future research on the pharmacological and toxicological aspects of Veratrum alkaloids.MethodsThis study focuses on five Veratrum alkaloids (cevadine, jervine, protoveratrine A, veratramine, and veratridine) in three Veratrum species (Veratrum album L., Veratrum californicum Durand, and Veratrum nigrum L.) collected from four German botanical gardens (Dresden, Leipzig, Marburg, and Schellerhau). A liquid–liquid extraction method and a sensitive high‐performance liquid chromatography coupled with tandem mass spectrometry (HPLC–MS/MS) method operating in multiple reaction monitoring (MRM) mode were applied for the alkaloid determination.ResultsQuantification revealed varying alkaloid concentrations among plant parts and Veratrum species in the μg/g to mg/g range. Protoveratrine A exhibited the highest content, while veratramine concentrations were generally lower. Especially in fruit, roots and rootstock of Veratrum album L. alkaloid concentrations were significant high.ConclusionThe developed HPLC‐MS/MS method successfully determined Veratrum alkaloid concentrations in plant samples. The study contributes valuable data on Veratrum alkaloid distribution in different species and plant parts, crucial for understanding their potential medicinal and toxicological significance.
Prenatal exome sequencing for morphologically normal fetus: Should we be doing it?
Authors: Gao Zhi , Zhu Xiaofan , Ren Huanan , Wang Yanfei , Hua Chunxiao , Kong Xiangdong 
Published: June 2024

AbstractObjectiveWe aimed to investigate the yield of prenatal exome sequencing (pES) in morphologically normal fetuses.MethodThis retrospective study analyzed 254 families with morphologically normal fetuses who underwent prenatal trio exome sequencing based on parental request between September 2020 and October 2023.ResultsOverall, abnormal findings were detected in 8 families (3.1%, 8/254) by pES. Among these, 6 families (2.3%, 6/254) were found to have fetuses affected with monogenic disorders (2 autosomal recessive conditions and 4 autosomal dominant conditions), while 2 families (0.8%, 2/254) were incidentally found to be couples at risk of having a future pregnancy with a recessive condition. Among the six fetuses detected with monogenic disorders, two fetuses carried a de novo variant in OPA1 and NF1, which are known to cause Optic atrophy 1 and Neurofibromatosis, respectively. One fetus was detected with a maternally inherited variant in PKD2 related to polycystic kidney disease 2 (not known to the mother until then). One fetus was detected with a maternally inherited variant in SDHB associated with Pheochromocytoma. Two fetuses carried compound heterozygous variants in NAGLU and GJB2 associated with Mucopolysaccharidosis type IIIB and Deafness, respectively. In the 2 families where parents were found to be carriers but the fetuses were unaffected, heterozygous variants in the GJB2 and SERPINB7 genes were detected in the parents, respectively, which are associated with deafness and palmoplantar keratoderma.ConclusionOur research indicated that pES can provide significant critical information for families with morphologically normal fetuses. Prenatal screening with exome sequencing requires careful management and detailed pre‐test and post‐test genetic counseling.
“Let's keep calm and breathe”—A mindfulness meditation program in school and its effects on children's behavior and emotional awareness: An Australian pilot study
Authors: Stapleton Peta , Dispenza Joseph , Douglas Angela , Dao Van , Kewin Sarah , Le Sech Kyra , Vasudevan Anitha 
Published: June 2024

AbstractThis study aimed to understand how mindfulness meditation affects young people by examining its impact on self‐regulation, happiness, emotional awareness, and school performance among two groups of school children. A 10‐week mindfulness program was conducted by a meditation expert for 552 children aged 4–8 (Group 1) and 287 children aged 9–11 (Group 2). Results for the 4–8 years group (Group 1) showed meditation predicted an increase in happiness (R2 = .003, p < .001) and self‐reported school performance (R2 = .005, p < .001) and a decrease in emotional (R2 = .017, p < .001) and behavioral difficulties (R2 = .009, p < .001); however, the effect sizes were small. In the 9–11 years group (Group 2), meditation predicted an increase in emotional awareness (R2 = .02, p < .001), and a decrease in emotional (R2 = .014, p < .001) and behavioral difficulties (R2 = .009, p < .001) as measured by scores from baseline to postintervention. For Group 2, there was no significant change in happiness over the 10 weeks. The findings support incorporating mindfulness meditation in schools, noting significant enhancements in self‐regulation with just 5 min of daily practice.
The effects of combining repetitive transcranial magnetic stimulation with task‐specific training on gait performance in individuals with Parkinson's disease: A review article
Authors: Niemrungruang Kanjana , Thanakamchokchai Jenjira , Pongmala Chatkaew , Khobkhun Fuengfa 
Published: June 2024

AbstractBackgroundParkinson's disease (PD) is a neurodegenerative disorder characterized by motor impairments, especially in the area of gait disturbances. Physiotherapy, with a focus on task‐specific training, has demonstrated a level of efficacy as regards alleviating symptoms and enhancing functional capabilities in individuals with PD. Repetitive Transcranial Magnetic Stimulation (rTMS) has emerged as a potential therapeutic intervention for improving motor functions in individuals with PD.AimsThis review article aims to investigate the effects of combining rTMS with task‐specific training on gait performance in individuals with PD.Materials and MethodsPubMed, Physiotherapy Evidence Database (PEDro), and Scopus were all searched for relevant studies. The focus of the search was on studies that investigated the efficacy of combining rTMS with task‐specific training to improve gait performance in individuals with PD.ResultsFour studies were identified as fulfilling the eligibility criteria and were included in the study. The combination of rTMS with specific treadmill training and weight‐bearing exercises can significantly enhance walking efficiency, including improvements in walking speed, self‐mobility, and step rate. In addition, the combination of rTMS and task‐specific training, such as treadmill‐based training, shows promise in enhancing gait performance in individuals with PD.Discussion and ConclusionHigh‐frequency rTMS targeting the primary motor cortex (or M1) can result in improved walking speed, self‐mobility, and step rate. However, limited research exists regarding low‐frequency stimulation of the supplementary motor area (SMA) in individuals with gait issues. Further research is required to determine the optimal parameters of rTMS, such as strength, frequency, and duration of stimulation and it is worth considering the incorporation of additional training modalities, including cognitive exercises.
Lytic transglycosylase Slt of Pseudomonas aeruginosa as a periplasmic hub protein
Authors: Avila‐Cobian Luis F. , De Benedetti Stefania , Hoshino Hidekazu , Nguyen Van T. , El‐Araby Amr M. , Sader Safaa , Hu Daniel D. , Cole Sara L. , Kim Choon , Fisher Jed F. , Champion Matthew M. , Mobashery Shahriar 
Published: June 2024

AbstractPeptidoglycan is a major constituent of the bacterial cell wall. Its integrity as a polymeric edifice is critical for bacterial survival and, as such, it is a preeminent target for antibiotics. The peptidoglycan is a dynamic crosslinked polymer that undergoes constant biosynthesis and turnover. The soluble lytic transglycosylase (Slt) of Pseudomonas aeruginosa is a periplasmic enzyme involved in this dynamic turnover. Using amber‐codon‐suppression methodology in live bacteria, we incorporated a fluorescent chromophore into the structure of Slt. Fluorescent microscopy shows that Slt populates the length of the periplasmic space and concentrates at the sites of septation in daughter cells. This concentration persists after separation of the cells. Amber‐codon‐suppression methodology was also used to incorporate a photoaffinity amino acid for the capture of partner proteins. Mass‐spectrometry‐based proteomics identified 12 partners for Slt in vivo. These proteomics experiments were complemented with in vitro pulldown analyses. Twenty additional partners were identified. We cloned the genes and purified to homogeneity 22 identified partners. Biophysical characterization confirmed all as bona fide Slt binders. The identities of the protein partners of Slt span disparate periplasmic protein families, inclusive of several proteins known to be present in the divisome. Notable periplasmic partners (KD < 0.5 μM) include PBPs (PBP1a, KD = 0.07 μM; PBP5 = 0.4 μM); other lytic transglycosylases (SltB2, KD = 0.09 μM; RlpA, KD = 0.4 μM); a type VI secretion system effector (Tse5, KD = 0.3 μM); and a regulatory protease for alginate biosynthesis (AlgO, KD < 0.4 μM). In light of the functional breadth of its interactome, Slt is conceptualized as a hub protein within the periplasm.
Kinetic and dynamical properties of truncated hemoglobins of the Antarctic bacterium Pseudoalteromonas haloplanktis TAC125
Authors: de Armiño Diego Javier Alonso , Di Lella Santiago , Montepietra Daniele , Delcanale Pietro , Bruno Stefano , Giordano Daniela , Verde Cinzia , Estrin Dario A. , Viappiani Cristiano , Abbruzzetti Stefania 
Published: June 2024

AbstractDue to the low temperature, the Antarctic marine environment is challenging for protein functioning. Cold‐adapted organisms have evolved proteins endowed with higher flexibility and lower stability in comparison to their thermophilic homologs, resulting in enhanced reaction rates at low temperatures. The Antarctic bacterium Pseudoalteromonas haloplanktis TAC125 (PhTAC125) genome is one of the few examples of coexistence of multiple hemoglobin genes encoding, among others, two constitutively transcribed 2/2 hemoglobins (2/2Hbs), also named truncated Hbs (TrHbs), belonging to the Group II (or O), annotated as PSHAa0030 and PSHAa2217. In this work, we describe the ligand binding kinetics and their interrelationship with the dynamical properties of globin Ph‐2/2HbO‐2217 by combining experimental and computational approaches and implementing a new computational method to retrieve information from molecular dynamic trajectories. We show that our approach allows us to identify docking sites within the protein matrix that are potentially able to transiently accommodate ligands and migration pathways connecting them. Consistently with ligand rebinding studies, our modeling suggests that the distal heme pocket is connected to the solvent through a low energy barrier, while inner cavities play only a minor role in modulating rebinding kinetics.
Pyriproxyfen enhances germline stem cell proliferation and reduces reproduction in Drosophila by up‐regulating juvenile hormone signaling
Authors: Khalid Muhammad Zaryab , Liu Jin , Zhang Jing , Yang Liying , Sun Zhipeng , Zhong Guohua 
Published: June 2024

AbstractBACKGROUNDPyriproxyfen is an insect growth regulator (IGR) that is effective against various types of insect pests. However, the molecular mechanism underlying pyriproxyfen effects on insect reproduction remains unclear. Thus, in this study, we attempted to uncover the mechanisms underlying the impact of pyriproxyfen on the reproductive system of the model organism Drosophila melanogaster.RESULTSA significant decrease in Drosophila reproduction was observed after pyriproxyfen treatment. The juvenile hormone (JH) titer was significantly increased (120.4%) in the ovary samples of pyriproxyfen‐treated flies. Likewise, the concentrations of key enzymes and the expression of key genes related to the JH signaling pathway were also increased in the pyriproxyfen‐treated group compared with the control group. Furthermore, pyriproxyfen treatment significantly increased (15.6%) the number of germline stem cells (GSCs) and significantly decreased (17%) the number of cystoblasts (CBs). However, no significant differences were observed in the number of somatic cells. We performed RNA interference (RNAi) on five key genes (Met, Tai, gce, ftz‐f1, and hairy) related to the JH signaling pathway in germ cells using the germ cell‐specific Gal4 driver. Interestingly, RNAi of the selected genes significantly decreased the number of both GSCs and CBs in pyriproxyfen‐treated transgenic flies. These results further validate that pyriproxyfen enhances GSC proliferation by up‐regulating JH signaling.CONCLUSIONOur results indicate that pyriproxyfen significantly decreases reproduction by affecting germ cells in female adult ovaries. The effect of pyriproxyfen on germ cell proliferation and differentiation is mediated by an increase in JH signaling. This study has significant implications for optimizing pest control strategies, developing sustainable agriculture practices, and understanding the mechanism of insecticide action. © 2024 Society of Chemical Industry.
SAAM II: A general mathematical modeling rapid prototyping environment
Authors: Perazzolo Simone 
Published: June 2024

AbstractSimulation Analysis and Modeling II (SAAM II) is a graphical modeling software used in life sciences for compartmental model analysis, particularly, but not exclusively, appreciated in pharmacokinetics (PK) and pharmacodynamics (PD), metabolism, and tracer modeling. Its intuitive “circles and arrows” visuals allow users to easily build, solve, and fit compartmental models without the need for coding. It is suitable for rapid prototyping of models for complex kinetic analysis or PK/PD problems, and in educating students and non‐modelers. Although it is straightforward in design, SAAM II incorporates sophisticated algorithms programmed in C to address ordinary differential equations, deal with complex systems via forcing functions, conduct multivariable regression featuring the Bayesian maximum a posteriori, perform identifiability and sensitivity analyses, and offer reporting functionalities, all within a single package. After 26 years from the last SAAM II tutorial paper, we demonstrate here SAAM II's updated applicability to current life sciences challenges. We review its features and present four contemporary case studies, including examples in target‐mediated PK/PD, CAR‐T‐cell therapy, viral dynamics, and transmission models in epidemiology. Through such examples, we demonstrate that SAAM II provides a suitable interface for rapid model selection and prototyping. By enabling the fast creation of detailed mathematical models, SAAM II addresses a unique requirement within the mathematical modeling community.
Information communication technology, globalization, and energy poverty: Prospects for sustainable development in the N‐11 countries
Authors: Wang Chenxi , Pan Xingguang , Wang Deli , Zafar Muhammad Wasif 
Published: June 2024

AbstractEnergy poverty is a significant barrier to sustainable development, affecting millions of people worldwide. However, technology offers innovative solutions that can bridge the energy gap and promote access to reliable and affordable energy services. In this study, we analyze the impact of ICT and globalization on energy poverty in N‐11 countries from 1990 to 2021, utilizing education, financial development, and economic growth as control variables. Results explain that the impact of ICT on energy poverty in lower quantiles appears to be relatively weak and positive, suggesting that it may be of limited effectiveness in reducing energy poverty in the most vulnerable populations. At higher quantiles, however, the impact becomes increasingly hostile, which suggests that higher ICT levels may exacerbate energy poverty among those who are already experiencing it. Energy poverty tends to decrease as globalization increases, as evidenced by the statistically significant negative coefficients across all quantiles. At the 10th percentile (Q0.1), an increase of one unit in globalization is associated with a reduction of 0.898 in energy poverty. Similarly, at the 90th percentile (Q0.9), an increase of one unit in globalization increases to 0.050 in energy poverty. It is possible to optimize resource utilization, reduce costs, and increase energy access through regional energy cooperation frameworks, such as cross‐border electricity grids or gas pipelines. In order to promote sustainable energy practices among citizens, the government should prioritize investing in clean energy projects, promoting energy conservation, and raising awareness of the importance of sustainable energy practices.
Harmonic Imaging of Stem Cells in Whole Blood at GHz Pixel Rate
Authors: Karpf Sebastian , Glöckner Burmeister Nina , Dubreil Laurence , Ghosh Shayantani , Hollandi Reka , Pichon Julien , Leroux Isabelle , Henkel Alessandra , Lutz Valerie , Jurkevičius Jonas , Latshaw Alexandra , Kilin Vasyl , Kutscher Tonio , Wiggert Moritz , Saavedra‐Villanueva Oscar , Vogel Alfred , Huber Robert A. , Horvath Peter , Rouger Karl , Bonacina Luigi 
Published: June 2024

AbstractThe pre‐clinical validation of cell therapies requires monitoring the biodistribution of transplanted cells in tissues of host organisms. Real‐time detection of these cells in the circulatory system and identification of their aggregation state is a crucial piece of information, but necessitates deep penetration and fast imaging with high selectivity, subcellular resolution, and high throughput. In this study, multiphoton‐based in‐flow detection of human stem cells in whole, unfiltered blood is demonstrated in a microfluidic channel. The approach relies on a multiphoton microscope with diffractive scanning in the direction perpendicular to the flow via a rapidly wavelength‐swept laser. Stem cells are labeled with metal oxide harmonic nanoparticles. Thanks to their strong and quasi‐instantaneous second harmonic generation (SHG), an imaging rate in excess of 10 000 frames per second is achieved with pixel dwell times of 1 ns, a duration shorter than typical fluorescence lifetimes yet compatible with SHG. Through automated cell identification and segmentation, morphological features of each individual detected event are extracted and cell aggregates are distinguished from isolated cells. This combination of high‐speed multiphoton microscopy and high‐sensitivity SHG nanoparticle labeling in turbid media promises the detection of rare cells in the bloodstream for assessing novel cell‐based therapies.
Feline sarcoptic mange in Poland: A case series of three cats
Authors: Szczepanik Marcin , Wilkolek Piotr , Kalisz Grzegorz , Szczepaniak Klaudiusz 
Published: June 2024

AbstractBackgroundSarcoptic mange is rare in cats. The main symptoms reported in cases of feline sarcoptic mange include crusty lesions and pruritus, although these may vary in severity among individuals.ObjectivesThis report describes three cats infested with Sarcoptes scabiei, all presenting with pruritus and excoriation.MethodsThe diagnosis was confirmed by microscopic observation of skin scrape samples.ResultsAll three cats were treated successfully using moxidectin and imidacloprid, selamectin and ivermectin, respectively.ConclusionsThe clinical presentation of feline scabies appears to be more variable in cats than in dogs. Infestation with S. scabiei should be considered a differential diagnosis for cats presenting with pruritic inflammatory skin disease.