bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular turnover and degradation of the most common missense cystathionine beta‐synthase variants causing homocystinuria
Authors: Mijatovic Ela , Ascenção Kelly , Szabo Csaba , Majtan Tomas 
Published: July 2024

AbstractHomocystinuria (HCU) due to cystathionine beta‐synthase (CBS) deficiency is the most common inborn error of sulfur amino acid metabolism. Recent work suggests that missense pathogenic mutations—regardless of their topology—cause instability of the C‐terminal regulatory domain, which likely translates into CBS misfolding, impaired assembly, and loss of function. However, it is unknown how instability of the regulatory domain translates into cellular CBS turnover and which degradation pathways are involved in CBS proteostasis. Here, we developed a human HEK293‐based cellular model lacking intrinsic CBS and stably overexpressing wild‐type (WT) CBS or its 10 most common missense HCU mutants. We found that HCU mutants, except the I278T variant, expressed similarly or better than CBS WT, with some of them showing impaired oligomerization, activity and response to allosteric activator S‐adenosylmethionine. Cellular stability of all HCU mutants, except P49L and A114V, was significantly lower than the stability of CBS WT, suggesting their increased degradation. Ubiquitination analysis of CBS WT and two representative CBS mutants (T191M and I278T) showed that proteasomal degradation is the major pathway for CBS disposal, with a minor involvement of lysosomal‐autophagic and endoplasmic reticulum‐associated degradation (ERAD) pathways for HCU mutants. Proteasomal inhibition significantly increased the half‐life and activity of T191M and I278T CBS mutants. Lysosomal and ERAD inhibition had only a minor impact on CBS turnover, but ERAD inhibition rescued the activity of T191M and I278T CBS mutants similarly as proteasomal inhibition. In conclusion, the present study provides new insights into proteostasis of CBS in HCU.
Population pharmacokinetic modeling of sufentanil in adult Korean patients undergoing cardiopulmonary bypass surgery
Authors: Khaowroongrueng Vipada , Son Kuk Hui , Lee Sang‐Min , Lee JiYeon , Park Chun‐Gon , Lee Seok In , Shin Dongseong , Shin Kwang‐Hee 
Published: July 2024

AbstractSufentanil is frequently used as an anesthetic agent in cardiac surgery owing to its cardiovascular safety and favorable pharmacokinetics. However, the pharmacokinetics profiles of sufentanil in patients undergoing cardiopulmonary bypass (CPB) surgery remain less understood, which is crucial for achieving the desired level of anesthesia and mitigating surgical complications. Therefore, this study aimed to develop a population pharmacokinetic model of sufentanil in patients undergoing CPB surgery and elucidate the clinical factors affecting its pharmacokinetic profile. Adult patients who underwent cardiac surgery with CPB and were administered sufentanil for anesthesia were enrolled. Arterial blood samples were collected to quantify plasma concentrations of sufentanil and clinical laboratory parameters, including inflammatory cytokines. A population pharmacokinetic model was established using nonlinear mixed‐effects modeling. Simulations were performed using the pharmacokinetic parameters of the final model. Overall, 20 patients were included in the final analysis. Sufentanil pharmacokinetics were modeled using a two‐compartment model, accounting for CPB effects. Sufentanil clearance increased 2.80‐fold during CPB and warming phases, while the central compartment volume increased 2.74‐fold during CPB. CPB was a significant covariate affecting drug clearance and distribution volume. No other significant covariates were identified despite increased levels of the inflammatory cytokines, including IL‐6, IL‐8, and TNF‐α during CPB. The simulation indicated a 30 μg loading dose and 40 μg/h maintenance infusion for target‐controlled infusion. Additionally, a bolus dose of 60 μg was added at CPB initiation to adjust for exposure changes during this phase. Considering the target sufentanil concentrations, a uniform dosing regimen was acceptable for effective analgesia.
Astragaloside IV protects renal tubular epithelial cells against oxidative stress‐induced injury by upregulating CPT1A‐mediated HSD17B10 lysine succinylation in diabetic kidney disease
Authors: Wang Meng , Li Qiurui , Wang Shang , Zuo Ling , Hai Yang , Yuan Su , Li Xuezhi , Huang Xuekuan , Yang Congwen , Yao Ling , Cao Wenfu , Zuo Guoqing , Wang Jianwei 
Published: July 2024

AbstractTubular injury and oxidative stress are involved in the pathogenesis of diabetic kidney disease (DKD). Astragaloside IV (ASIV) is a natural antioxidant. The effects and underlying molecular mechanisms of ASIV on DKD have not been elucidated. The db/db mice and high‐glucose‐stimulated HK2 cells were used to evaluate the beneficial effects of ASIV in vivo and in vitro. Succinylated proteomics was used to identify novel mechanisms of ASIV against DKD and experimentally further validated. ASIV alleviated renal dysfunction and proteinuria, downregulated fasting blood glucose, and upregulated insulin sensitivity in db/db mice. Meanwhile, ASIV alleviated tubular injury, oxidative stress, and mitochondrial dysfunction in vivo and in vitro. Mechanistically, ASIV reversed downregulated 17beta‐hydroxysteroid dehydrogenase type 10 (HSD17B10) lysine succinylation by restoring carnitine palmitoyl‐transferase1alpha (Cpt1a or CPT1A) activity in vivo and in vitro. Molecular docking and cell thermal shift assay revealed that ASIV may bind to CPT1A. Molecular dynamics simulations demonstrated K99 succinylation of HSD17B10 maintained mitochondrial RNA ribonuclease P (RNase P) stability. The K99R mutation of HSD17B10 induced oxidative stress and disrupted its binding to CPT1A or mitochondrial ribonuclease P protein 1 (MRPP1). Importantly, ASIV restored the interaction between HSD17B10 and MRPP1 in vivo and in vitro. We also demonstrated that ASIV reversed high‐glucose‐induced impaired RNase P activity in HK2 cells, which was suppressed upon K99R mutation of HSD17B10. These findings suggest that ASIV ameliorates oxidative stress‐associated proximal tubular injury by upregulating CPT1A‐mediated K99 succinylation of HSD17B10 to maintain RNase P activity.
Facile Preparation of Chitosan/Carnauba Wax Emulsion‐Based Coatings for Hydrophobic and Oleophobic Cellulose‐Based Food Packaging
Authors: Zou Yang , Zhang Yanfen , Zhang Hui , Cao Bin , Luo Zixin , Duan Huawei 
Published: July 2024

ABSTRACTStudies have shown that fluoridated reagents for oil and water resistance are harmful to the human bodies and the environment. Consequently, the developments of nontoxic, environmentally friendly, fluorine‐free and degradable materials have received increasing attentions. Here, we introduce a novel method for fabricating a hydrophobic and oleophobic paper‐based packaging material through the application of chitosan/carnauba wax emulsions. These emulsions were prepared via high‐shear homogenization, blending melted carnauba wax with chitosan in acetic acid aqueous solutions. The stable chitosan/carnauba wax emulsion with particle size of 430 nm was prepared at the chitosan concentration of 1.5 wt%, the carnauba wax concentration of 8 wt% and temperature of 85 °C. After 10 g/m2 of chitosan/carnauba wax emulsion was applied to the paper surface, the oil and water resistance of the paper was significantly improved. The experimental results of kit rating value, oil contact angle, Cobb60 value and water contact angle were 9.5 ± 0.6, 86.6 ± 2.1°, 8.90 ± 1.62 g/m2 and 123.5 ± 2.6°, respectively. The application of chitosan/carnauba wax emulsion coating on papers provided a significantly lower water vapour transmission rate (WVTR, 78.45 ± 18.92 g/m2·24 h) and oxygen transmission rate (OTR, 94.26 ± 20.21 g/m2·24 h) as compared to the original paper, which met the needs of strawberry packaging.
Ensemble weather forecast post‐processing with a flexible probabilistic neural network approach
Authors: Mlakar Peter , Merše Janko , Faganeli Pucer Jana 
Published: July 2024

AbstractEnsemble forecast post‐processing is a necessary step in producing accurate probabilistic forecasts. Many post‐processing methods operate by estimating the parameters of a predetermined probability distribution; others operate on a per‐lead‐time or per‐station basis. All of the aforementioned factors either limit the expressive power of the methods in question or require additional models, one for each lead time and station. We propose a novel, neural network‐based method that produces forecasts for all lead times jointly and requires a single model for all stations. We incorporate normalizing spline flows as flexible parametric distribution estimators, which enables us to model complex forecast distributions. Furthermore, we demonstrate the effectiveness of our method in the context of the EUPPBench benchmark, where we conduct 2‐m temperature forecast post‐processing for stations in a subregion of Europe. We show that our novel method exhibits state‐of‐the‐art performance on the benchmark, improving upon other well‐performing entries. Additionally, by providing a detailed comparison of three variants of our novel post‐processing method, we elucidate the reasons why our method outperforms per‐lead‐time‐based approaches and approaches with distributional assumptions.
Estimating the gain of increasing the ensemble size from analytical considerations
Authors: Christiansen Bo 
Published: July 2024

AbstractModel ensembles may provide estimates of uncertainties arising from unknown initial conditions and model deficiencies. Often, the ensemble mean is taken as the best estimate, and quantities such as the mean‐squared error between model mean and observations decrease with the number of ensemble members. But the ensemble size is often limited by available resources, and so some idea of how many ensemble members that are needed before the error has saturated would be advantageous. The behaviour with ensemble size is often estimated by producing subsamples from a large ensemble. But this strategy requires that this large ensemble is already available. Fortunately, in many situations, the dependence on ensemble size follows simple analytical relations when the quantity under interest (such as the mean‐squared error between ensemble mean and observations) is calculated over many grid points or time points. This holds both for ensemble means and the related sampling variance. Here, we present such relations and demonstrate how they can be used to estimate the gain of increasing the ensemble. Whereas previous work has mainly focused on the size of the model ensemble, we recognize that uncertainties in observations play a role. We therefore also study the effect of using the mean of an ensemble of reanalyses. We show how the analytical relations can be used to estimate the point where the gain of increasing the size of the model ensemble is dwarfed by the gain of increasing the number of reanalyses. We demonstrate these points using two climate model ensembles: a large multimodel ensemble and a large single‐model initial‐condition ensemble.
Transbronchial lung cryobiopsy under real‐time radial EBUS: First report on a novel twist of the classical technique
Authors: Anagnostopoulos Nektarios , Petrarulo Simone , Ravaglia Claudia , Dubini Alessandra , Piciucchi Sara , Stratakos Grigoris , Poletti Venerino 
Published: July 2024

AbstractTransbronchial lung cryobiopsy (TBLC) is a relatively new technique for obtaining lung biopsies, known for being the least invasive method while offering a high diagnostic yield, a favourable safety profile, and a significant reduction in morbidity, mortality, and hospital stay length compared to surgical lung biopsy. Radial‐EBUS (r‐EBUS) represent a cornerstone modality for accessing ‘invisible’ peripheral pulmonary lesions. However, a major drawback of these techniques is the lack of ‘real‐time’ visualization of the biopsy being obtained. In this case report, we present a young woman who was referred to us with a cough, haemoptysis, and a non‐resolving lung consolidation. She underwent TBLC under real‐time rEBUS guidance. This clinical case demonstrates that, in specific clinical scenarios, TBLC with real‐time rEBUS is an excellent diagnostic tool.
Characterizing climate pathways using feature importance on echo state networks
Authors: Goode Katherine , Ries Daniel , McClernon Kellie 
Published: July 2024

AbstractThe 2022 National Defense Strategy of the United States listed climate change as a serious threat to national security. Climate intervention methods, such as stratospheric aerosol injection, have been proposed as mitigation strategies, but the downstream effects of such actions on a complex climate system are not well understood. The development of algorithmic techniques for quantifying relationships between source and impact variables related to a climate event (i.e., a climate pathway) would help inform policy decisions. Data‐driven deep learning models have become powerful tools for modeling highly nonlinear relationships and may provide a route to characterize climate variable relationships. In this paper, we explore the use of an echo state network (ESN) for characterizing climate pathways. ESNs are a computationally efficient neural network variation designed for temporal data, and recent work proposes ESNs as a useful tool for forecasting spatiotemporal climate data. However, ESNs are noninterpretable black‐box models along with other neural networks. The lack of model transparency poses a hurdle for understanding variable relationships. We address this issue by developing feature importance methods for ESNs in the context of spatiotemporal data to quantify variable relationships captured by the model. We conduct a simulation study to assess and compare the feature importance techniques, and we demonstrate the approach on reanalysis climate data. In the climate application, we consider a time period that includes the 1991 volcanic eruption of Mount Pinatubo. This event was a significant stratospheric aerosol injection, which acts as a proxy for an anthropogenic stratospheric aerosol injection. We are able to use the proposed approach to characterize relationships between pathway variables associated with this event that agree with relationships previously identified by climate scientists.
Synthesis of Pyridine Dicarboxylic Acid Functionalized and Crosslinked to Polyvinyl Alcohol/polyamide for Thorium Capturing From Aqueous Solution
Authors: Hendy Mohamed A. , Kashar Tahani I. , Allam Eman M. , Gado Mohamed A. , Yahia Naema S. , Cheira Mohamed F. 
Published: July 2024

AbstractThorium harms humans and the environment. Mining can release thorium‐containing waste. This study aims to simplify the production of a novel poly‐adsorbent by mixing pyridine dicarboxylic acid, polyvinyl alcohol, and polyamide and first removing thorium from the solution. Various analytical methods were used to characterize the produced dicarboxylic acid/polyvinyl alcohol/polyamide poly‐adsorbent. The practical conditions on adsorption effectiveness evaluated to pH 3.5, 60 mg poly‐adsorbent, 60 min. Th(IV) uptake for poly‐adsorbent is 107.3 mg/g. The linear and nonlinear uptake for the pseudo‐second‐order is closer to the practical uptake (107.71 mg/g). Hence, the kinetic analysis verified the sorption mechanism. Also, the uptake of linear (107.64 mg/g) and nonlinear (108.63 mg/g) types for the Langmuir isotherm is closer to the practical uptake (107.71 mg/g); thus, the sorption isotherm was suitably utilizing Langmuir modeling. Thermodynamic studies proved that the sorption is spontaneous, exothermic, and random due to the negative ΔG°, negative ΔH°, and positive ΔS° during the thorium adsorption process on poly‐adsorbent. In addition, the regeneration ability of poly‐adsorbent was tested utilizing 1.5 M H2SO4. After six cycles, the poly‐adsorbent showed about 83 % regeneration efficacy. The results confirmed that the dicarboxylic acid/polyvinyl alcohol/polyamide poly‐adsorbent might be effective in removing Th(IV) from the watery solution.
In‐Plane Mesoporous 3D Flower‐Like Mo2Ti2C3Clx MXene Anodes for Li‐Ion Batteries: From Structure to Performance
Authors: Gandla Dayakar , Li Qian , Zhou Yun'an , Yan Yihao , Liu Zhaoxi , Chen Jia , Tan Daniel Q. 
Published: July 2024

AbstractMXenes are known for their exceptional electrical conductivity and surface functionality, gaining interest as promising anode materials for Li‐ion batteries. However, conventional 2D multilayered MXenes often exhibit limited electrochemical applicability due to slow ion transport kinetics and low structural stability. Addressing these challenges, this study develops a 3D flower‐type double transition metal MXene, Mo2Ti2C3Clx, with precisely engineered in‐plane mesoporosity using HF‐free Lewis acid‐assisted molten salt method, coupled with intercalation and freeze‐drying. The molar ratio of Lewis acid to eutectic salts is meticulously controlled to create the mesoporosity, which is preserved through freeze‐drying. Molecular dynamics (MD) simulations assess the impact of in‐plane pore size on the structure and transport dynamics of electrolyte components. Density functional theory (DFT) shows that chlorine surface functional groups significantly reduce Li‐ion diffusion barriers, thereby enhancing ion transport and battery performance. Electrochemical evaluations reveal that small‐sized (2–5 nm) mesoporous Mo2Ti2C3Clx achieves a specific capacity of 324 mAh g−1 at 0.2 A g−1 and maintains 97% capacity after 500 cycles at 0.5 A g−1, outperforming larger‐pored (10 nm) and non‐porous variants. This research highlights a scalable strategy for designing mesoporous materials that optimize ion transport and structural stability, essential for advancing next‐generation high‐performance energy storage solutions.
Cardiac Tissue Engineering: A Journey from Scaffold Fabrication to In Vitro Characterization
Authors: Ketabat Farinaz , Alcorn Jane , Kelly Michael E. , Badea Ildiko , Chen Xiongbiao 
Published: July 2024

Cardiac tissue engineering has been rapidly evolving with diverse applications, ranging from the repair of fibrotic tissue caused by “adverse remodeling,” to the replacement of specific segments of heart tissue, and ultimately to the creation of a whole heart. The repair or replacement of cardiac tissue often involves the development of tissue scaffolds or constructs and the subsequent assessment of their performance and functionality. For this, the design and/or selection of biomaterials, and cell types, scaffold fabrication, and in vitro characterizations are the first starting points, yet critical, to ensure success in subsequent implantation in vivo. This highlights the importance of scaffold fabrication and in vitro experiments/characterization with protocols for cardiac tissue engineering. Yet, a comprehensive and critical review of these has not been established and documented. As inspired, herein, the latest development and advances in scaffold fabrication and in vitro characterization for cardiac tissue engineering are critically reviewed, with focus on biomaterials, cell types, additive manufacturing techniques for scaffold fabrication, and common in vitro characterization techniques or methods. This article would be of benefit to the ones who are working on cardiac tissue engineering by providing insights into the scaffold fabrication and in vitro investigations.
High‐purity La3‐xTe4 Material with Superior Thermoelectric Performance Synthesized via Te‐vapor Transport and Solid‐State Diffusion
Authors: Pan Yu‐Lin , Cao Yan , Qiao Feng , Xia Sheng‐Qing , Liu Xiao‐Cun , Zhou Tian , Hou Xu‐Feng 
Published: July 2024

AbstractLa3‐xTe4 is a very promising high‐temperature candidate applied in next‐generation Radioisotope Thermoelectric Generators (RTGs). Conventional synthesis of such materials is based on the mechanochemical method, which makes the sample difficult to purify due to the high‐energy ball milling. In this report, a novel synthetic method is developed, which utilizes Te‐vapor transport and solid‐phase diffusion to efficiently produce the RE3‐xTe4 phases (RE = La, Ce, Pr, Nd). Notably, this method obviates the requirement for high‐energy ball‐milling instruments, conventionally indispensable in the mechanochemical syntheses. For as‐synthesized La2.74Te4 material, a high figure of merit of 1.5 is achieved at 1073 K, owning to the reduced electronic thermal conductivity with metal impurities well eliminated.
New aquatic insects from the Miocene of Australia with notes on the ecology and ontogeny of a new species of Chaoborus (Diptera, Chaoboridae)
Authors: Baranov Viktor , Frese Michael , Beattie Robert , Djokic Tara , McCurry Matthew R. 
Published: July 2024

AbstractWe describe a diverse aquatic insect assemblage from McGraths Flat, a Miocene Lagerstätte in central New South Wales, Australia that includes representatives of Sialidae, Limoniidae, Chironomidae and Chaoboridae. The aquatic insect fossils from this deposit consist predominantly of larvae. These include a new species of phantom midge (Chaoborus, Chaoboridae), three morphotypes of non‐biting midges (Chironomidae), one morphotype of cranefly (Limoniidae) and one morphotype of alderfly (Sialidae). The large number of fossil specimens enabled us to study the ontogeny of the new midge species. We discerned growth rates in fossil larvae, using morphometry of all four instars of Chaoborus. The simultaneous presence of taxa associated with still water and taxa associated with flowing water supports the hypothesis that McGraths Flat was deposited in an isolated water body (oxbow lake/billabong) with influence from a river during high water events.
A Cartridge Structure Facilitates Clinical Mass Spectrometry Pretreatment and Can be Integrated Into a High‐Throughput Instrument
Authors: He Xiaofei , Feng Mengxue , Xu Xiaofeng , Zhao Hong , Qian Xueqing 
Published: July 2024

ABSTRACTLiquid chromatography–triple quadrupole mass spectrometry (LC–MS/MS) is becoming an increasingly essential analytical technique in many fields, such as food, environmental, biochemical, pharmaceutical, and clinical chemistry. The testing matrices, such as plasma and serum, cannot usually be sent directly to the LC–MS/MS system because of the large number of unrelated substances in addition to target analytes in samples, such as cells, tissues, and proteins. Protein precipitation (PPT) is the most utilized pretreatment method in clinical analysis because of its ease of use; its performance always involves the separation of the liquid phase from the solid phase, in which the most commonly used manipulation is centrifugation. However, there is an upper limit of throughput for centrifugation, and the cost and difficulty of integrating centrifugation into automatic equipment are usually high. To solve the drawbacks of the current PPT method, we developed a cartridge structure that can omit the centrifugation step in PPT, which, in turn, can facilitate the incorporation of the PPT method into an automatic clinical pretreatment procedure for LC–MS/MS. We used vitamin D analysis as a representative application in our endeavor to develop a centrifugation‐free PPT method that can be easily applied to a new automatic clinical pretreatment procedure.