bluuebunny/crossref_metadata_2025 huggingface dataset:
Multivalent interactions between molecular components involved in fast endophilin mediated endocytosis drive protein phase separation
Authors: Mondal Samsuzzoha , Narayan Karthik , Botterbusch Samuel , Powers Imania , Zheng Jason , James Honey Priya , Jin Rui , Baumgart Tobias
Published: August 2022

A specific group of transmembrane receptors, including the β1-adrenergic receptor (β1-AR), is internalized through a non-clathrin pathway known as Fast Endophilin Mediated Endocytosis (FEME). A key question is: how does the endocytic machinery assemble and how is it modulated by activated receptors during FEME. Here we show that endophilin, a major regulator of FEME, undergoes a phase transition into liquid-like condensates, which facilitates the formation of multi-protein assemblies by enabling the phase partitioning of endophilin binding proteins. The phase transition can be triggered by specific multivalent binding partners of endophilin in the FEME pathway such as the third intracellular loop (TIL) of the β1-AR, and the C-terminal domain of lamellipodin (LPD). Other endocytic accessory proteins can either partition into, or target interfacial regions of, these condensate droplets, and LPD also phase separates with the actin polymerase VASP. On the membrane, TIL promotes protein clustering in the presence of endophilin and LPD C-terminal domain. Our results demonstrate how the multivalent interactions between endophilin, LPD, and TIL regulate protein assembly formation on the membrane, providing mechanistic insights into the priming and initiation steps of FEME.
Structure of the human NK cell NKR-P1:LLT1 receptor:ligand complex reveals clustering in the immune synapse
Authors: Bláha Jan , Skálová Tereza , Kalousková Barbora , Skořepa Ondřej , Cmunt Denis , Grobárová Valéria , Pazicky Samuel , Poláchová Edita , Abreu Celeste , Stránský Jan , Kovaľ Tomáš , Dušková Jarmila , Zhao Yuguang , Harlos Karl , Hašek Jindřich , Dohnálek Jan , Vaněk Ondřej
Published: August 2022

Signaling by the human C-type lectin-like receptor, natural killer (NK) cell inhibitory receptor NKR-P1, has a critical role in many immune-related diseases and cancer. C-type lectin-like receptors have weak affinities to their ligands; therefore, setting up a comprehensive model of NKR-P1-LLT1 interactions that considers the natural state of the receptor on the cell surface is necessary to understand its functions. Here we report the crystal structures of the NKR-P1 and NKR-P1:LLT1 complexes, which provides evidence that NKR-P1 forms homodimers in an unexpected arrangement to enable LLT1 binding in two modes, bridging two LLT1 molecules. These interaction clusters are suggestive of an inhibitory immune synapse. By observing the formation of these clusters in solution using SEC-SAXS analysis, by dSTORM super-resolution microscopy on the cell surface, and by following their role in receptor signaling with freshly isolated NK cells, we show that only the ligation of both LLT1 binding interfaces leads to effective NKR-P1 inhibitory signaling. In summary, our findings collectively support a model of NKR-P1:LLT1 clustering, which allows the interacting proteins to overcome weak ligand-receptor affinity and to trigger signal transduction upon cellular contact in the immune synapse.
The CCTG PA.7 phase II trial of gemcitabine and nab-paclitaxel with or without durvalumab and tremelimumab as initial therapy in metastatic pancreatic ductal adenocarcinoma
Authors: Renouf Daniel J. , Loree Jonathan M. , Knox Jennifer J. , Topham James T. , Kavan Petr , Jonker Derek , Welch Stephen , Couture Felix , Lemay Frederic , Tehfe Mustapha , Harb Mohammed , Aucoin Nathalie , Ko Yoo-Joung , Tang Patricia A. , Ramjeesingh Ravi , Meyers Brandon M. , Kim Christina A. , Du Pan , Jia Shidong , Schaeffer David F. , Gill Sharlene , Tu Dongsheng , O’Callaghan Chris J
Published: August 2022

Immunotherapy-based monotherapy treatment in metastatic pancreatic ductal adenocarcinoma (mPDAC) has shown limited benefit outside of the mismatch repair deficiency setting, while safety and efficacy of combining dual-checkpoint inhibitor immunotherapy with chemotherapy remains uncertain. Here, we present results from the CCTG PA.7 study (NCT02879318), a randomized phase II trial comparing gemcitabine and nab-paclitaxel with and without immune checkpoint inhibitors durvalumab and tremelimumab in 180 patients with mPDAC. The primary endpoint was overall survival. Secondary endpoints included progression-free survival and objective response rate. Results of the trial were negative as combination immunotherapy did not improve survival among the unselected patient population (p = 0.72) and toxicity was limited to elevation of lymphocytes in the combination immunotherapy group (p = 0.02). Exploratory baseline circulating tumor DNA (ctDNA) sequencing revealed increased survival for patients with KRAS wildtype tumors in both the combination immunotherapy (p = 0.001) and chemotherapy (p = 0.004) groups. These data support the utility of ctDNA analysis in PDAC and the prognostic value of ctDNA-based KRAS mutation status.
Asymmetric 1,4-functionalization of 1,3-enynes via dual photoredox and chromium catalysis
Authors: Zhang Feng-Hua , Guo Xiaochong , Zeng Xianrong , Wang Zhaobin
Published: August 2022

The merger of photoredox and transition-metal catalysis has evolved as a robust platform in organic synthesis over the past decade. The stereoselective 1,4-functionalization of 1,3-enynes, a prevalent synthon in synthetic chemistry, could afford valuable chiral allene derivatives. However, tremendous efforts have been focused on the ionic reaction pathway. The radical-involved asymmetric 1,4-functionalization of 1,3-enynes remains a prominent challenge. Herein, we describe the asymmetric three-component 1,4-dialkylation of 1,3-enynes via dual photoredox and chromium catalysis to provide chiral allenols. This method features readily available starting materials, broad substrate scope, good functional group compatibility, high regioselectivity, and simultaneous control of axial and central chiralities. Mechanistic studies suggest that this reaction proceeds through a radical-involved redox-neutral pathway.
Pneumolysin boosts the neuroinflammatory response to Streptococcus pneumoniae through enhanced endocytosis
Authors: Hupp Sabrina , Förtsch Christina , Graber Franziska , Mitchell Timothy J. , Iliev Asparouh I.
Published: August 2022

In pneumococcal meningitis, bacterial growth in the cerebrospinal fluid results in lysis, the release of toxic factors, and subsequent neuroinflammation. Exposure of primary murine glia toStreptococcus pneumoniaelysates leads to strong proinflammatory cytokine and chemokine production, blocked by inhibition of the intracellular innate receptor Nod1. Lysates enhance dynamin-dependent endocytosis, and dynamin inhibition reduces neuroinflammation, blocking ligand internalization. Here we identify the cholesterol-dependent cytolysin pneumolysin as a pro-endocytotic factor in lysates, its elimination reduces their proinflammatory effect. Only pore-competent pneumolysin enhances endocytosis in a dynamin-, phosphatidylinositol-3-kinase- and potassium-dependent manner. Endocytic enhancement is limited to toxin-exposed parts of the membrane, the effect is rapid and pneumolysin permanently alters membrane dynamics. In a murine model of pneumococcal meningitis, mice treated with chlorpromazine, a neuroleptic with a complementary endocytosis inhibitory effect show reduced neuroinflammation. Thus, the dynamin-dependent endocytosis emerges as a factor in pneumococcal neuroinflammation, and its enhancement by a cytolysin represents a proinflammatory control mechanism.
Midkine expression by stem-like tumor cells drives persistence to mTOR inhibition and an immune-suppressive microenvironment
Authors: Tang Yan , Kwiatkowski David J. , Henske Elizabeth P.
Published: August 2022

mTORC1 is hyperactive in multiple cancer types1,2. Here, we performed integrative analysis of single cell transcriptomic profiling, paired T cell receptor (TCR) sequencing, and spatial transcriptomic profiling on Tuberous Sclerosis Complex (TSC) associated tumors with mTORC1 hyperactivity, and identified a stem-like tumor cell state (SLS) linked to T cell dysfunction via tumor-modulated immunosuppressive macrophages. Rapamycin and its derivatives (rapalogs) are the primary treatments for TSC tumors, and the stem-like tumor cells showed rapamycin resistance in vitro, reminiscent of the cytostatic effects of these drugs in patients. The pro-angiogenic factor midkine (MDK) was highly expressed by the SLS population, and associated with enrichment of endothelial cells in SLS-dominant samples. Inhibition of MDK showed synergistic benefit with rapamycin in reducing the growth of TSC cell lines in vitro and in vivo. In aggregate, this study suggests an autocrine rapamycin resistance mechanism and a paracrine tumor survival mechanism via immune suppression adopted by the stem-like state tumor cells with mTORC1 hyperactivity.
Spatially patterned hydrogen peroxide orchestrates stomatal development in Arabidopsis
Authors: Shi Wen , Wang Lingyan , Yao Lianmei , Hao Wei , Han Chao , Fan Min , Wang Wenfei , Bai Ming-Yi
Published: August 2022

Stomatal pores allow gas exchange between plant and atmosphere. Stomatal development is regulated by multiple intrinsic developmental and environmental signals. Here, we show that spatially patterned hydrogen peroxide (H2O2) plays an essential role in stomatal development. H2O2 is remarkably enriched in meristemoids, which is established by spatial expression patterns of H2O2-scavenging enzyme CAT2 and APX1. SPEECHLESS (SPCH), a master regulator of stomatal development, directly binds to the promoters of CAT2 and APX1 to repress their expression in meristemoid cells. Mutations in CAT2 or APX1 result in an increased stomatal index. Ectopic expression of CAT2 driven by SPCH promoter significantly inhibits the stomatal development. Furthermore, H2O2 activates the energy sensor SnRK1 by inducing the nuclear localization of the catalytic α-subunit KIN10, which stabilizes SPCH to promote stomatal development. Overall, these results demonstrate that the spatial pattern of H2O2 in epidermal leaves is critical for the optimal stomatal development in Arabidopsis.
Magnetically assisted drop-on-demand 3D printing of microstructured multimaterial composites
Authors: Liu Wing Chung , Chou Vanessa Hui Yin , Behera Rohit Pratyush , Le Ferrand Hortense
Published: August 2022

Microstructured composites with hierarchically arranged fillers fabricated by three-dimensional (3D) printing show enhanced properties along the fillers’ alignment direction. However, it is still challenging to achieve good control of the filler arrangement and high filler concentration simultaneously, which limits the printed material’s properties. In this study, we develop a magnetically assisted drop-on-demand 3D printing technique (MDOD) to print aligned microplatelet reinforced composites. By performing drop-on-demand printing using aqueous slurry inks while applying an external magnetic field, MDOD can print composites with microplatelet fillers aligned at set angles with high filler concentrations up to 50 vol%. Moreover, MDOD allows multimaterial printing with voxelated control. We showcase the capabilities of MDOD by printing multimaterial piezoresistive sensors with tunable performances based on the local microstructure and composition. MDOD thus creates a large design space to enhance the mechanical and functional properties of 3D printed electronic or sensing devices using a wide range of materials.
The state prediction method of the silk dryer based on the GA-BP model
Authors: Jiang Hao , Yu Zegang , Wang Yonghua , Zhang Baowei , Song Jiuxiang , Wei Jingdian
Published: August 2022

Considering the under-maintenance and over-maintenance of existing equipment maintenance methods, this paper studies a Condition Based Maintenance method for silk dryers. The entropy method is used to eliminate the influence of subjective factors to more objectively reflect the weight of different input parameters; optimizing the number of nodes in the hidden layer of the network to improve the prediction accuracy; and using the GA-BP neural network to establish a state prediction model of the equipment to solve the disadvantages of the BP neural network, for example, unstable prediction, easily falling into local optimum, and slow global search ability. Simulation experiments show that this method can effectively compensate for the shortcomings of the existing maintenance methods, and provide an effective scientific basis for dryer state maintenance.
A new perspective on Workload Control by measuring operating performances through an economic valorization
Authors: Mezzogori Davide , Romagnoli Giovanni , Zammori Francesco
Published: August 2022

Workload Control (WLC) is a production planning and control system conceived to reduce queuing times of job-shop systems, and to offer a solution to the lead time syndrome; a critical issue that often bewilders make-to-order manufacturers. Nowadays, advantages of WLC are unanimously acknowledged, but real successful stories are still limited. This paper starts from the lack of a consistent way to assess performance of WLC, an important burden for its acceptance in the industry. As researchers often put more focus on the performance measures that better confirm their hypotheses, many measures, related to different WLC features, have emerged over years. However, this excess of measures may even mislead practitioners, in the evaluation of alternative production planning and control systems. To close this gap, we propose quantifying the main benefit of WLC in economic terms, as this is the easiest, and probably only way, to compare different and even conflicting performance measures. Costs and incomes are identified and used to develop an overall economic measure that can be used to evaluate, or even to fine tune, the operating features of WLC. The quality of our approach is finally demonstrated via simulation, considering the 6-machines job-shop scenario typically adopted as benchmark in technical literature.
Task-dependent learning and memory deficits in the TgF344-AD rat model of Alzheimer’s disease: three key timepoints through middle-age in females
Authors: Bernaud Victoria E. , Bulen Haidyn L. , Peña Veronica L. , Koebele Stephanie V. , Northup-Smith Steven N. , Manzo Alma A. , Valenzuela Sanchez Maria , Opachich Zorana , Ruhland Ashley M. , Bimonte-Nelson Heather A.
Published: August 2022

The TgF344 rat model of Alzheimer’s disease (AD) provides a comprehensive neuropathology presentation, with age-dependent development of tau tangles, amyloid-beta (A$${\beta}$$
β
) plaques, neuronal loss, and increased gliosis. The behavioral trajectory of this model, particularly relating to spatial learning and memory, has yet to be fully characterized. The current experiment evaluated spatial working and reference memory performance, as well as several physiological markers of health, at 3 key age points in female TgF344-AD rats: 6-months, 9-months, and 12-months. At 6 months of age, indications of working and reference memory impairments were observed in transgenic (Tg) rats on the water radial-arm maze, a complex task that requires working and reference memory simultaneously; at 12 months old, Tg impairments were observed for two working memory measures on this task. Notably, no impairments were observed at the 9-month timepoint on this maze. For the Morris maze, a measure of spatial reference memory, Tg rats demonstrated significant impairment relative to wildtype (WT) controls at all 3 age-points. Frontal cortex, entorhinal cortex, and dorsal hippocampus were evaluated for A$${\beta}$$
β
1–42 expression via western blot in Tg rats only. Analyses of A$${\beta}$$
β
1–42 expression revealed age-dependent increases in all 3 regions critical to spatial learning and memory. Measures of physiological health, including heart, uterine, and body weights, revealed unique age-specific outcomes for female Tg rats, with the 9-month timepoint identified as critical for further research within the trajectory of AD-like behavior, physiology, and pathology.
Outcomes of endoscopic mucosal resection for large superficial non-ampullary duodenal adenomas
Authors: Amoyel Maxime , Belle Arthur , Dhooge Marion , Ali Einas Abou , Pellat Anna , Hallit Rachel , Terris Benoit , Prat Frédéric , Chaussade Stanislas , Coriat Romain , Barret Maximilien
Published: August 2022

Endoscopic mucosal resection (EMR) is the recommended treatment for superficial non-ampullary duodenal epithelial tumors larger than 6 mm. This endoscopic technique carries a high risk of adverse events. Our aim was to identify the risk factors for adverse events following EMR for non-ampullary duodenal adenomatous lesions. We retrospectively analyzed a prospectively collected database of consecutive endoscopic resections for duodenal lesions at a tertiary referral center for therapeutic endoscopy. We analyzed patients with non-ampullary duodenal adenomatous lesions ≥ 10 mm resected by EMR, and searched for factors associated with adverse events after EMR. 167 duodenal adenomatous lesions, with a median size of 25 (25–40) mm, were resected by EMR between January 2015 and December 2020. Adverse events occurred in 37/167 (22.2%) after endoscopic resection, with 29/167 (17.4%) delayed bleeding, 4/167 (2.4%) immediate perforation and 4/167 (2.4%) delayed perforation. In logistic regression, the size of the lesion was the only associated risk factor of adverse events (OR = 2.81, 95% CI [1.27; 6.47], p = 0.012). Adverse events increased mean hospitalization time (7.7 ± 9 vs. 1.9 ± 1 days, p < 0.01). None of the currently recommended preventive methods, particularly clips, affected the adverse event rate. EMR of centimetric and supracentimetric duodenal adenomatous lesions carries a high risk of adverse events, increasing with the size of the lesion and with no benefit from any preventive method. These results suggest that these procedures should be performed in expert centers, and underline the need for novel endoscopic tools to limit the rate of adverse events.
A high birefringence liquid crystal for lenses with large aperture
Authors: Bennis N. , Jankowski T. , Strzezysz O. , Pakuła A. , Zografopoulos D. C. , Perkowski P. , Sánchez-Pena J. M. , López-Higuera J. M. , Algorri J. F.
Published: August 2022

This work presents the application of an experimental nematic liquid crystal (LC) mixture (1929) in a large aperture lens. The LC material is composed of terphenyl and biphenyl derivatives compounds with an isothiocyanate terminal group and fluorinated lateral substituents. The substitution with a strongly polar isothiocyanate group and an aromatic rigid core provides $$\pi$$
π
-electron coupling, providing high birefringence ($$\Delta n = 0.3375$$

Δ
n
=
0.3375

at 636 nm and 23 °C) and low viscosity ($$\eta$$
η
= 17.03 mPa s). In addition, it also shows high values of birefringence at near infrared (0.318 at 1550 nm). The synthesis process is simple when comparing materials with high melting temperatures. The excellent properties of this LC mixture are demonstrated in a large aperture LC-tunable lens based on a transmission electrode structure. Thanks to the particular characteristics of this mixture, the optical power is high. The high birefringence makes this LC of specific interest for lenses and optical phase modulators and devices, both in the visible and infrared regions.
Prehospital diagnostic algorithm for acute coronary syndrome using machine learning: a prospective observational study
Authors: Takeda Masahiko , Oami Takehiko , Hayashi Yosuke , Shimada Tadanaga , Hattori Noriyuki , Tateishi Kazuya , Miura Rie E. , Yamao Yasuo , Abe Ryuzo , Kobayashi Yoshio , Nakada Taka-aki
Published: August 2022

Rapid and precise prehospital recognition of acute coronary syndrome (ACS) is key to improving clinical outcomes. The aim of this study was to investigate a predictive power for predicting ACS using the machine learning-based prehospital algorithm. We conducted a multicenter observational prospective study that included 10 participating facilities in an urban area of Japan. The data from consecutive adult patients, identified by emergency medical service personnel with suspected ACS, were analyzed. In this study, we used nested cross-validation to evaluate the predictive performance of the model. The primary outcomes were binary classification models for ACS prediction based on the nine machine learning algorithms. The voting classifier model for ACS using 43 features had the highest area under the receiver operating curve (AUC) (0.861 [95% CI 0.775–0.832]) in the test score. After validating the accuracy of the model using the external cohort, we repeated the analysis with a limited number of selected features. The performance of the algorithms using 17 features remained high AUC (voting classifier, 0.864 [95% CI 0.830–0.898], support vector machine (radial basis function), 0.864 [95% CI 0.829–0.887]) in the test score. We found that the machine learning-based prehospital algorithms showed a high predictive power for predicting ACS.
Large extensional earthquakes push-up terrific amount of fluids
Authors: Chiarabba Claudio , De Gori Pasquale , Valoroso Luisa , Petitta Marco , Carminati Eugenio
Published: August 2022

How large earthquakes are triggered is a key question in Earth science, and the role played by fluid pressure seems to be crucial. Nevertheless, evaluation of involved fluid volumes is seldom investigated, if not unaccounted for. Moreover, fluid flow along fault zones is a driving factor for seismicity migration, episodic heat and chemical transport. Here we show that time repeated (4D) seismic tomography resolves changes of Vp and Vp/Vs during the Mw6.2 2009 L’Aquila normal faulting sequence, that indicate a post-failure fluid migration from hypocentral depths to the surface, with a volume estimated between 5 and 100 × 106 m3 rising at rates up to 100 m/day. This amount inferred by tomograms is surprisingly consistent with the about 50 × 106 m3 surplus water volume additionally measured at spring discharge, spread in time and space along the 700 km2-wide regional carbonate fractured aquifer. Fluids were pushed-up within a huge volume across the fault and expelled from the area of large coseismic slip. Such quantities of fluids liberated during earthquakes add unprecedented constraints to the discussion on the role of fluids during and possibly before earthquake, as well as to the potential impact on the pristine high-quality drinkable groundwater, possibly affecting the biodiversity of groundwater dependent ecosystems too.
Validation of reference genes as an internal control for studying Avena sativa–Puccinia coronata interaction by RT-qPCR
Authors: Sowa Sylwia , Sozoniuk Magdalena , Toporowska Joanna , Kowalczyk Krzysztof , Paczos-Grzęda Edyta
Published: August 2022

In this study we evaluated eleven candidate reference genes in Avena sativa during compatible and incompatible interactions with two different pathotypes of Puccinia coronata f. sp. avenae in six time points post-inoculation. The identification of genes with high expression stability was performed by four algorithms (geNorm, NormFinder, BestKeeper and ΔCt method). The results obtained confirmed that the combination of two genes would be sufficient for reliable normalization of the expression data. In general, the most stable in the tested plant-pathogen system were HNR (heterogeneous nuclear ribonucleoprotein 27C) and EF1A (elongation factor 1-alpha). ARF (ADP-ribosylation factor) and EIF4A (eukaryotic initiation factor 4A-3) could also be considered as exhibiting high expression stability. CYP (cyclophilin) was shown by all assessment methods to be the worst candidate for normalization in this dataset. To date, this is the first report of reference genes selection in A. sativa–P. coronata interaction system. Identified reference genes enable reliable and comprehensive RT-qPCR analysis of oat gene expression in response to crown rust infection. Understanding the molecular mechanisms involved in the host–pathogen interactions may expand knowledge of durable resistance strategies beneficial to modern oat breeding.
Inflammatory cytokines directly disrupt the bovine intestinal epithelial barrier
Authors: Crawford Charles K. , Lopez Cervantes Veronica , Quilici Mary L. , Armién Aníbal G. , Questa María , Matloob Muhammad S. , Huynh Leon D. , Beltran Aeelin , Karchemskiy Sophie J. , Crakes Katti R. , Kol Amir
Published: August 2022

The small intestinal mucosa constitutes a physical barrier separating the gut lumen from sterile internal tissues. Junctional complexes between cells regulate transport across the barrier, preventing water loss and the entry of noxious molecules or pathogens. Inflammatory diseases in cattle disrupt this barrier; nonetheless, mechanisms of barrier disruption in cattle are poorly understood. We investigated the direct effects of three inflammatory cytokines, TNFα, IFNγ, and IL-18, on the bovine intestinal barrier utilizing intestinal organoids. Flux of fluorescein isothiocyanate (FITC)-labeled dextran was used to investigate barrier permeability. Immunocytochemistry and transmission electron microscopy were used to investigate junctional morphology, specifically tortuosity and length/width, respectively. Immunocytochemistry and flow cytometry was used to investigate cellular turnover via proliferation and apoptosis. Our study shows that 24-h cytokine treatment with TNFα or IFNγ significantly increased dextran permeability and tight junctional tortuosity, and reduced cellular proliferation. TNFα reduced the percentage of G2/M phase cells, and IFNγ treatment increased cell apoptotic rate. IL-18 did not directly induce significant changes to barrier permeability or cellular turnover. Our study concludes that the inflammatory cytokines, TNFα and IFNγ, directly induce intestinal epithelial barrier dysfunction and alter the tight junctional morphology and rate of cellular turnover in bovine intestinal epithelial cells.
Catalytic activity and mechanistic investigation of 1D 2-Picolinic acid based Cu(II) coordination polymer in the selective construction of 1,4-disubstituted triazoles
Authors: Aier Merangmenla , Gayen Firdaus Rahaman , Puzari Amrit
Published: August 2022

The catalytic activity of 1D 2-Picolinic acid based Cu (II) coordination polymer (CP1) in click reaction was evaluated to generate 1,4-disubstituted 1,2,3-triazoles selectively. The CP1 catalyst loading of 2 mol% was applied successfully in the reaction for primary azides with diverse functionalities of terminal alkynes in green solvent (EG/H2O). Moreover, the one-pot, multicomponent click reaction involving benzyl bromide, sodium azide, and phenylacetylene was also catalyzed by CP1. The findings show that 1D 2-Picolinic acid based Cu (II) coordination polymer catalytic systems are highly efficient for green click triazoles synthesis. DFT calculation supported the plausible mechanism involved in the CP1 catalyzed click reaction.
Modeling a 3-D multiscale blood-flow and heat-transfer framework for realistic vascular systems
Authors: Amare Rohan , Hodneland Erlend , Roberts Jeremy A. , Bahadori Amir A. , Eckels Steven
Published: August 2022

Modeling of biological domains and simulation of biophysical processes occurring in them can help inform medical procedures. However, when considering complex domains such as large regions of the human body, the complexities of blood vessel branching and variation of blood vessel dimensions present a major modeling challenge. Here, we present a Voxelized Multi-Physics Simulation (VoM-PhyS) framework to simulate coupled heat transfer and fluid flow using a multi-scale voxel mesh on a biological domain obtained. In this framework, flow in larger blood vessels is modeled using the Hagen–Poiseuille equation for a one-dimensional flow coupled with a three-dimensional two-compartment porous media model for capillary circulation in tissue. The Dirac distribution function is used as Sphere of Influence (SoI) parameter to couple the one-dimensional and three-dimensional flow. This blood flow system is coupled with a heat transfer solver to provide a complete thermo-physiological simulation. The framework is demonstrated on a frog tongue and further analysis is conducted to study the effect of convective heat exchange between blood vessels and tissue, and the effect of SoI on simulation results.
Validity and reliability of accelerations and orientations measured using wearable sensors during functional activities
Authors: Cudejko Tomasz , Button Kate , Al-Amri Mohammad
Published: August 2022

Wearable sensors may enable the assessment of movement in a real-world setting, but they are not yet a standard practice in the analysis of movement due to the unknown accuracy and reliability with respect to different functional activities. Here, we established the concurrent validity and test–retest reliability of accelerations and orientations measured using affordable novel sensors during squats, jumps, walking and stair ambulation. In this observational study, participants underwent three data collection sessions during one day. Accelerations and orientations from sacrum, thigh and shank were collected using these sensors and already validated gold-standard sensors as the criterion method. We assessed validity by comparing the similarity of signal waveforms with the Linear Fit Method and by comparing mean differences in range values with the Bland–Altman plots. Reliability was assessed by calculating interclass correlation coefficient and standard error of measurements of the range values. Concurrent validity was from fair to excellent in 91% of the cases for accelerations and in 84.4% for orientations. Test–retest reliability of accelerations was from fair to excellent in 97% of cases when the sensors were attached by a researcher, and in 84.4% of cases when the sensors were attached by participants. Test–retest reliability of orientations was from fair to excellent in 88.9% of cases when the sensors were attached by a researcher, and in 68.9% of cases when the sensors were attached by participants. In conclusion, the new affordable sensors provide accurate measures of accelerations and orientations during multiple functional activities in healthy adults. Reliability of the orientations may depend on the ability to replicate the same position of the sensor under test–retest conditions.
Unveiling new perspective of phylogeography, genetic diversity, and population dynamics of Southeast Asian and Pacific chickens
Authors: Godinez Cyrill John P. , Layos John King N. , Yamamoto Yoshio , Kunieda Tetsuo , Duangjinda Monchai , Liao Lawrence M. , Huang Xun-He , Nishibori Masahide
Published: August 2022

The complex geographic and temporal origins of chicken domestication have attracted wide interest in molecular phylogeny and phylogeographic studies as they continue to be debated up to this day. In particular, the population dynamics and lineage-specific divergence time estimates of chickens in Southeast Asia (SEA) and the Pacific region are not well studied. Here, we analyzed 519 complete mitochondrial DNA control region sequences and identified 133 haplotypes with 70 variable sites. We documented 82.7% geographically unique haplotypes distributed across major haplogroups except for haplogroup C, suggesting high polymorphism among studied individuals. Mainland SEA (MSEA) chickens have higher overall genetic diversity than island SEA (ISEA) chickens. Phylogenetic trees and median-joining network revealed evidence of a new divergent matrilineage (i.e., haplogroup V) as a sister-clade of haplogroup C. The maximum clade credibility tree estimated the earlier coalescence age of ancestral D-lineage (i.e., sub-haplogroup D2) of continental chickens (3.7 kya; 95% HPD 1985–4835 years) while island populations diverged later at 2.1 kya (95% HPD 1467–2815 years). This evidence of earlier coalescence age of haplogroup D ancestral matriline exemplified dispersal patterns to the ISEA, and thereafter the island clade diversified as a distinct group.
Simultaneously induced mutations in eIF4E genes by CRISPR/Cas9 enhance PVY resistance in tobacco
Authors: Le Ngoc Thu , Tran Huyen Thi , Bui Thao Phuong , Nguyen Giang Thu , Van Nguyen Doai , Ta Dong Thi , Trinh Duy Dinh , Molnar Attila , Pham Ngoc Bich , Chu Ha Hoang , Do Phat Tien
Published: August 2022

Tobacco is an important commercial crop and a rich source of alkaloids for pharmaceutical and agricultural applications. However, its yield can be reduced by up to 70% due to virus infections, especially by a potyvirus Potato virus Y (PVY). The replication of PVY relies on host factors, and eukaryotic translation initiation factor 4Es (eIF4Es) have already been identified as recessive resistance genes against potyviruses in many plant species. To investigate the molecular basis of PVY resistance in the widely cultivated allotetraploid tobacco variety K326, we developed a dual guide RNA CRISPR/Cas9 system for combinatorial gene editing of two clades, eIF4E1 (eIF4E1-S and eIF4E1-T) and eIF4E2 (eIF4E2-S and eIF4E2-T) in the eIF4E gene family comprising six members in tobacco. We screened for CRISPR/Cas9-induced mutations by heteroduplex analysis and Sanger sequencing, and monitored PVYO accumulation in virus challenged regenerated plants by DAS-ELISA both in T0 and T1 generations. We found that all T0 lines carrying targeted mutations in the eIF4E1-S gene displayed enhanced resistance to PVYO confirming previous reports. More importantly, our combinatorial approach revealed that eIF4E1-S is necessary but not sufficient for complete PVY resistance. Only the quadruple mutants harboring loss-of-function mutations in eIF4E1-S, eIF4E1-T, eIF4E2-S and eIF4E2-T showed heritable high-level resistance to PVYO in tobacco. Our work highlights the importance of understanding host factor redundancy in virus replication and provides a roadmap to generate virus resistance by combinatorial CRISPR/Cas9-mediated editing in non-model crop plants with complex genomes.
Platelet abnormalities in patients with Parkinson's disease undergoing preoperative evaluation for deep brain stimulation
Authors: Chou Sheng-Che , Tai Chun-Hwei , Tseng Sheng-Hong
Published: August 2022

Normal hemostatic function is important for reduction of the risk of intracranial hemorrhage during stereotactic neurosurgery including deep brain stimulation (DBS) surgery. This study investigates the hemostatic function in patients with Parkinson’s disease (PD) undergoing preoperative evaluation for DBS, with emphasis on the number and function of platelets. In 107 PD patients, only one had abnormal activated partial prothrombin time and normal prothrombin time. Among the other 106 patients, six (5.7%) had only thrombocytopenia, seven (6.6%) only prolonged bleeding time (BT), and 14 (13.2%) only prolonged closure time (CT) of platelet function analyzer 100 (PFA-100). Totally, 34 of the 106 patients (32.1%) had at least one of three kinds of platelet abnormalities. No factor was found to be associated with the occurrence of platelet abnormalities except that abnormal platelet group and prolonged BT subgroup had more patients using selegiline and lower UPDRS-III motor subscore with medication off than normal platelet group (p < 0.05). The use of selegiline was significantly correlated with prolonged BT (p = 0.0041) and platelet abnormality (p = 0.0197). Therefore, it is important to have detailed evaluation of the hemostatic function for PD patients undergoing preoperative evaluation for DBS, especially the platelet number and function.
Adsorption behavior of rhamnolipid modified magnetic Co/Al layered double hydroxide for the removal of cationic and anionic dyes
Authors: Kheradmand Asiyeh , Negarestani Mehrdad , Kazemi Sima , Shayesteh Hadi , Javanshir Shahrzad , Ghiasinejad Hossein
Published: August 2022

In the present research, magnetic rhamnolipid-Co/Al layered double hydroxide (MR-LDH) was synthesized to uptake methylene blue (MB) and reactive orange 16 (RO16) from aqueous solution. The main parameters, including pH, adsorbent dosage, contact time, and initial analyte concentration, were optimized to achieve the best adsorption efficiency. Accordingly, the elimination of MB on MR-LDH is improved in the basic medium due to the electrostatic interactions between the negative charge of MR-LDH and the positive charge of MB dye. In contrast, the acidic medium (pH = 3) was favored for RO16 adsorption because of hydrogen bonding between the protonated form of azo dye and protonated hydroxyl groups at the surface of MR-LDH. The calculated maximum adsorption capacities for MB and RO16 were 54.01 and 53.04 mg/g at 313 K, respectively. The Langmuir model, which assumes monolayer adsorption on the adsorbent surface, provides the best explanation for the adsorption of both dyes (R2 = 0.9991 for MB and R2 = 0.9969 for RO16). Moreover, the pseudo-second-order kinetic model best described the adsorption process for MB (R2 = 0.9970) and RO16 (R2 = 0.9941). The proposed adsorbent maintains stable adsorption performance for four consecutive cycles. After each adsorption process, MR-LDH is easily separated by an external magnet. The findings show that MR-LDH was found to be an excellent adsorbent for the removal of both cationic and anionic organic dyes from aqueous solutions.
The health digital twin to tackle cardiovascular disease—a review of an emerging interdisciplinary field
Authors: Coorey Genevieve , Figtree Gemma A. , Fletcher David F. , Snelson Victoria J. , Vernon Stephen Thomas , Winlaw David , Grieve Stuart M. , McEwan Alistair , Yang Jean Yee Hwa , Qian Pierre , O’Brien Kieran , Orchard Jessica , Kim Jinman , Patel Sanjay , Redfern Julie
Published: August 2022

Potential benefits of precision medicine in cardiovascular disease (CVD) include more accurate phenotyping of individual patients with the same condition or presentation, using multiple clinical, imaging, molecular and other variables to guide diagnosis and treatment. An approach to realising this potential is the digital twin concept, whereby a virtual representation of a patient is constructed and receives real-time updates of a range of data variables in order to predict disease and optimise treatment selection for the real-life patient. We explored the term digital twin, its defining concepts, the challenges as an emerging field, and potentially important applications in CVD. A mapping review was undertaken using a systematic search of peer-reviewed literature. Industry-based participants and patent applications were identified through web-based sources. Searches of Compendex, EMBASE, Medline, ProQuest and Scopus databases yielded 88 papers related to cardiovascular conditions (28%, n = 25), non-cardiovascular conditions (41%, n = 36), and general aspects of the health digital twin (31%, n = 27). Fifteen companies with a commercial interest in health digital twin or simulation modelling had products focused on CVD. The patent search identified 18 applications from 11 applicants, of which 73% were companies and 27% were universities. Three applicants had cardiac-related inventions. For CVD, digital twin research within industry and academia is recent, interdisciplinary, and established globally. Overall, the applications were numerical simulation models, although precursor models exist for the real-time cyber-physical system characteristic of a true digital twin. Implementation challenges include ethical constraints and clinical barriers to the adoption of decision tools derived from artificial intelligence systems.
Artesunate drug-loaded 2D nano-shuttle landing on RBCs infected with malaria parasites
Authors: Kim Ji-Yeong , Shin Hyun-Il , Lee Sang-Eun , Piao Huiyan , Rejinold N. Sanoj , Choi Goeun , Choy Jin-Ho
Published: August 2022

2D NPs could play a role as a nano-shuttle to deliver an AS− drug to the red blood cells (RBCs) infected with malaria parasites.
Cu/CuxO@C nanocomposites as efficient electrodes for high-performance supercapacitor devices
Authors: Guo Yuxuan , Chen Changyun , Wang Yumeng , Hong Ye , Wu Hua , Wang Kuaibing , Niu Dongdong , Zhang Cheng , Zhang Qichun
Published: August 2022

Four different Cu/CuxO@C (x = 1 and 2) composites have been obtained and their electrochemical properties have also been investigated and compared.
[SMe3]2[Bi2Ag2I10], a silver iodido bismuthate with an unusually small band gap
Authors: Möbs Jakob , Pan Sudip , Tonner-Zech Ralf , Heine Johanna
Published: August 2022

The synthesis and characterization of a new silver iodido bismuthate with a low optical band gap highlights the decisive role of building unit connectivity for the optical properties in this class of materials.
Expression of concern: Protective role of air potato (Dioscorea bulbifera) of yam family in myocardial ischemic reperfusion injury
Authors: Ross Philippa
Published: August 2022

Expression of concern for ‘Protective role of air potato (Dioscorea bulbifera) of yam family in myocardial ischemic reperfusion injury’ Food Funct., 2010, 1, 278–283, https://doi.org/10.1039/C0FO00048E.
Novel hydrolytically stable Lewis acidic ionic liquid catalyst system for polybutylene succinate (PBS) synthesis
Authors: Savitha K. S. , Senthil Kumar M. , Jagadish R. L.
Published: August 2022

A new Lewis acidic ionic liquid catalyst system with improved catalytic activity and hydrolytic stability has been developed for the synthesis of poly(butylene succinate). Improved thermal stability of the final polymer is an added advantage of our new catalyst system.
Pyrazole-containing pharmaceuticals: target, pharmacological activity, and their SAR studies
Authors: Li Guangchen , Cheng Yifu , Han Chi , Song Chun , Huang Niu , Du Yunfei
Published: August 2022

This review paper provides an overview of all the existing drugs bearing a pyrazole nucleus that have been approved or in clinical trials, involving their pharmacological activities and SAR studies.
The persistence length of linear surfactants modulates the self-assembly of reverse micelles and their diffusion in nonpolar solvents
Authors: Hernández Velázquez J. D. , Santos-Santos J. , Gama Goicochea A.
Published: August 2022

The self-assembly of linear model surfactants into reverse micelles (RMs) in a nonpolar solvent is studied here for two surfactant lengths, through numerical simulations.
Integrating machine learning interpretation methods for investigating nanoparticle uptake during seed priming and its biological effects
Authors: Yu Hengjie , Zhao Zhilin , Liu Da , Cheng Fang
Published: August 2022

Integration approaches of machine learning interpretation can promote the understanding of seed nanopriming which can facilitate sustainable agriculture.
Topochemical synthesis of Mn2O3/TiO2 and MnTiO3/TiO2 nanocomposites as lithium-ion battery anodes with fast Li+ migration and giant pseudocapacitance via the mesocrystalline effect
Authors: Wang Xing , Cheng Weijie , Hu Jiaqiao , Yu Han , Kong Xingang , Uemura Shinobi , Kusunose Takafumi , Feng Qi
Published: August 2022

Mesocrystalline Mn2O3/TiO2 and MnTiO3/TiO2 exhibit a much higher discharge–charge specific capacity than their polycrystalline nanocomposites due to the mesocrystalline effect.
Base-promoted cyclization reaction of o-isothiocyanato arylacetylenes and aroylacetonitriles: easy access to benzo[d][1,3]thiazines
Authors: Shen Jian , Li Shumin , Yao Zhenyu , Lin Shenghui , Cui Xiuling
Published: August 2022

A green and efficient synthesis of benzo[d][1,3]thiazines has been achieved via a base-promoted cyclization reaction of o-isothiocyanato arylacetylenes with aroylacetonitriles with 100% atom economy.
Antroxazole A, an oxazole-containing chamigrane dimer from the fungusAntrodiella albocinnamomeawith immunosuppressive activity
Authors: He Juan , Yu Wei-Wei , Isaka Masahiko , Cox Russell J. , Liu Ji-Kai , Feng Tao
Published: August 2022

Antroxazole A is a novel chamigrane dimer featuring with a dihydrooxazole moiety fromAntrodiella albocinnamomea. It inhibits LPS-induced proliferation of B lymphocyte cells with an IC50value of 16.3 μM.
Facile strategy to incorporate amidoxime groups into elastomers toward self-crosslinking and self-reinforcement
Authors: Tian Chenru , Feng Haoran , Qiu Yuchen , Zhang Ganggang , Tan Tianwei , Zhang Liqun
Published: August 2022

Amidoxime modification of NBR and the formation of a multi-crosslinking network structure by self-crosslinking of AO-NBR.
On-purpose design of dual active sites in single V atom anchored C2N nanosheets for propane dehydrogenation catalysis
Authors: Yang Yingke , Wang Jiawen , Lin Haiping , Dong Huilong , Li Youyong
Published: August 2022

On-purpose design of V–N dual active sites with single V atom anchored on C2N nanosheet can efficiently promote both the catalytic activity and selectivity during propane dehydrogenation (PDH) catalysis, as revealed by first-principle calculations.
Isothiourea-catalysed enantioselective annulation of 2-aminobenzothiophenes with α,β-unsaturated anhydrides
Authors: Niu Cheng , Xie Dong-Hua , Du Da-Ming
Published: August 2022

An isothiourea-catalysed asymmetric Michael/lactamization cascade reaction of 2-aminobenzothiophenes and α,β-unsaturated anhydrides for the enantioselective synthesis of benzothienopiperidones with high stereoselectivities was developed.
Applications of iron pincer complexes in hydrosilylation reactions
Authors: Nihala Rasheed , Hisana Kalathingal Nasreen , Afsina C. M. A. , Anilkumar Gopinathan
Published: August 2022

Iron pincer complexes are efficient in catalyzing various organic reactions with excellent selectivity and functional group tolerance at moderate reaction conditions. This review focuses on the applications of iron pincer complexes in hydrosilylation reactions.
Solid-solution reaction suppresses the Jahn–Teller effect of potassium manganese hexacyanoferrate in potassium-ion batteries
Authors: Liu Bingqiu , Zhang Qi , Ali Usman , Li Yiqian , Hao Yuehan , Zhang Lingyu , Su Zhongmin , Li Lu , Wang Chungang
Published: August 2022

The hollow KMnHCF nanospheres that are organized by numerous ultrasmall KMnHCF nanocube subunits (9 nm) replace the traditional phase transition of KMnHCF by a solid-solution reaction, which effectively suppress the Jahn–Teller effect.
Revealing the chemical structure-dependent carrier trapping in one-dimensional antimony selenide photovoltaic materials
Authors: Cao Rui , Cai Huiling , Lian Weitao , Tang Rongfeng , Xiang Yinan , Wang Yan , Chen Tao
Published: August 2022

Our results illustrate the absence of self-trapping in Sb2Se3, and the maximum transient trap states are ∼1020 cm−3.
A zwitterionic silver nanoparticle-incorporating injectable hydrogel with a durable and efficient antibacterial effect for accelerated wound healing
Authors: Xiang Jun , Bai Yangjing , Huang Yingchun , Lang Shiying , Li Juan , Ji Ying , Peng Biyu , Liu Gongyan
Published: August 2022

A facile stabilization strategy for silver nanoparticles is developed for an antibacterial and injectable hydrogel to promote wound healing.
Efficiency of thermo–photocatalytic production of hydrogen from biomolecules: a multifaceted perspective
Authors: Gómez-Cerezo María Natividad , Barba-Nieto Irene , Fernández-García Marcos , Kubacka Anna
Published: August 2022

Measuring and interpreting the efficiency of a thermo–photocatalytic reaction is key in the quest to define synergy for chemical reactions taking place under dual thermo–photo excitation.