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Model selection for water quality forecasting depends on many factors including analyst expertise and cost, stakeholder involvement and expected performance. Water quality forecasting in arid river basins is especially challenging given the importance of protecting beneficial uses in these environments and the livelihood of agricultural communities. In the agriculture‐dominated San Joaquin River Basin of California, real‐time salinity management (RTSM) is a state‐sanctioned program that helps to maximize allowable salt export while protecting existing basin beneficial uses of water supply. The RTSM strategy supplants the federal total maximum daily load (TMDL) approach that could impose fines associated with exceedances of monthly and annual salt load allocations of up to $1 million per year based on average year hydrology and salt load export limits. The essential components of the current program include the establishment of telemetered sensor networks, a web‐based information system for sharing data, a basin‐scale salt load assimilative capacity forecasting model and institutional entities tasked with performing weekly forecasts of river salt assimilative capacity and scheduling west‐side drainage export of salt loads. Web‐based information portals have been developed to share model input data and salt assimilative capacity forecasts together with increasing stakeholder awareness and involvement in water quality resource management activities in the river basin. Two modeling approaches have been developed simulta-neously. The first relies on a statistical analysis of the relationship between flow and salt concentra-tion at three compliance monitoring sites and the use of these regression relationships for forecast-ing. The second salt load forecasting approach is a customized application of the Watershed Analysis Risk Management Framework (WARMF), a watershed water quality simulation model that has been configured to estimate daily river salt assimilative capacity and to provide decision support for real‐time salinity management at the watershed level. Analysis of the results from both model-based forecasting approaches over a period of five years shows that the regression‐based forecasting model, run daily Monday to Friday each week, provided marginally better performance. However, the regression‐based forecasting model assumes the same general relationship between flow and salinity which breaks down during extreme weather events such as droughts when water allocation cutbacks among stakeholders are not evenly distributed across the basin. A recent test case shows the utility of both models in dealing with an exceedance event at one compliance monitoring site recently introduced in 2020.

In this study, a closed-cell aluminum foam was filled into the interspaces of a sandwich panel with corrugated cores to form a composite structure. The novel structure is expected to have enhanced foam-filled cores with high specific strength and energy absorption capacity. An out-of-plane compressive load under low-velocity impact was experimentally and numerically carried out on both the empty and foam-filled sandwich panels as well as on the aluminum foam. It is found that the empty corrugated sandwich panel has poor energy absorption capacity due to the core member buckling compared to that of the aluminum foam. However, by the filling of the aluminum foam, the impact load resistance of the corrugated panel was increased dramatically. The loading-time response of the foam-filled panel performs a plateau region like the aluminum foam, which has been proved to be an excellent energy absorption material. Numerical results demonstrated that the aluminum foam filling can decrease the corrugated core member defects sensitivity and increase its stability dramatically. The plastic energy dissipation of the core member for the foam-filled panel is much higher than that of the empty one due to the reduced buckling wavelength caused by the aluminum foam filling. [ABSTRACT FROM AUTHOR]

Background: Interpreting genetic variants remains a challenge in prostate cancer (PCa). Although many annotation tools are available for prioritizing causal variants, the clinical relevance of these variants is rarely studied., Methods: We collected a cohort study that included 274 PCa patients from June 2017 to December 2020 and sequenced 19 DNA damage repair (DDR) genes in these patients and explored the clinical consequence of these different approaches. We also examined all-cause and PCa-specific survival in DDR gene mutation carriers compared to non-carriers after androgen receptor (AR)-directed therapy., Results: We identified 13 variants from 19 DDR genes in a total of 14 (5.1%) patients who had at least one presumed pathogenic mutation using different annotation methods. Four variants were annotated as pathogenic, 11 variants were predicted as protein-truncating variants (PTVs), four variants received proxy-deleterious (Combined Annotation-Dependent Depletion scores of > 30), and only one variant was identified as a pathogenic variant or as having a functional effect by all three methods. PCa patients with PTVs were significantly associated with early onset, high cancer stage, and a worse response to AR-directed treatment. However, patients carrying a proxy-deleterious variant were only associated with a higher T (tumor) stage and N (node) stage than those without such a variant, but not associated with other clinical characteristics. In patients treated with AR-directed therapy, patients with a PTV showed an increased risk of all-cause death (adjusted hazard ratio (aHR) = 3.51, 95% confidence interval (CI): 1.06 ~ 11.56) and PCa-specific death (aHR = 4.49, 95% CI: 1.87 ~ 10.77) compared to non-PTV carriers after adjustment. We were unable to examine gene-specific risks due to the small number of patients., Conclusions: PTVs may assist in guiding treatment and early screening in PCa, while population-specific data for pathogenic variants are still being amassed., (© 2024. The Author(s).)

Purpose: The formalin-ethyl acetate (FEA) concentration method is commonly used in routine clinical practice to detect parasite eggs in feces. This procedure involves extraction of oil with the organic solvent ethyl acetate (EA), which reduces fecal sediment and provides a cleaner background for microscopic analysis. However, clinically, some sediment failed to float after EA treatment., Methods: Hexane, commonly used in the food oil extraction from oilseeds did not float the feces. Gas chromatography-mass spectrometry (GC-MS) analysis showed that neither the amount of the oil nor the classes of the oil determined was differed whether hexane or EA was used to float the feces. Oil red, Bodipy and Calcofluor staining showed that the unabsorbed oil droplets in the fecal sediment were trapped within the leaf structure. HCl or acetic acid was added to see if the acid residue could dissolve the cellulose of the leaf to promote the bulk float., Results: Our result showed that the fecal bulk contained the loosened mesophyll cell wall. The addition of acid residues improved fecal bulk float. The proximity of cellulose fiber to EA, but not hexane, may enhance the efficacy of oil extraction from cellulose., Conclusion: This is the first report that the interaction of cellulose with ethyl acetate in fecal solution has an effect on bulk float. This study improves the understanding of fecal bulk flotation and may assist in the visualization of parasite eggs in clinical practice with non-floating fecal samples in the FEA concentration method., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Selective ablation of cancer cells by ultrasound would be transformative for cancer therapy, but has not yet been possible. A key challenge is that cancerous and non-cancerous cells typically have similar acoustic impedance and are thus indistinguishable as materials in their responses to ultrasound. However, in certain cancers, cytoskeletal and nuclear lamin structures differ between healthy and malignant cells, opening the possibility of exploiting structural differences that manifest as different vibrational responses. To assess the possibility that the nuclei of certain cancerous cells might vibrate at different frequencies, we measured sizes and effective indentation moduli of a range of cancerous and non-cancerous cells from several cell lines and regions of the brain, and estimated the natural frequencies for nuclear vibration. Results suggest a potential difference in natural frequency for nuclear vibration between certain cancerous and non-cancerous cells, on the order of tens of kHz. This gap is potentially sufficient for selective ablation and motivates future experimentation on these specific cell types., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Obesity is a global health challenge that causes metabolic dysregulation and increases the risk of various chronic diseases. The gut microbiome is crucial in modulating host energy metabolism, immunity, and inflammation and is influenced by dietary factors. Gac fruit (Momordica cochinchinensis), widely consumed in Southeast Asia, has been proven to have various biological activities. However, the composition and effect of crude gac aril polysaccharides (GAP) on obesity and gut microbiota disturbed by high-fat diet (HFD) remain to be elucidated. Compositional analysis showed that GAP contains high oligosaccharides, with an average of 7-8 saccharide units. To mimic clinical obesity, mice were first made obese by feeding HFD for eight weeks. GAP intervention was performed from week 9 to week 20 in HFD-fed mice. Our results showed that GAP inhibited body weight gain, eWAT adipocyte hypertrophy, adipokine derangement, and hyperlipidemia in HFD-induced obese mice. GAP improved insulin sensitivity, impaired glucose tolerance, and hepatic steatosis. GAP modulated the gut microbiota composition and reversed the HFD-induced dysbiosis of at least 20 genera. Taken together, GAP improves metabolic health and modulates the gut microbiome to relieve obesity risk factors, demonstrating the potential of dietary GAP for treating obesity-associated disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The double-bag theory in modern anatomy suggests that structures with coatings are commonly found in human body at various length scales, such as osteocyte processes covered by pericellular matrix and bones covered by muscle tissue. To understand the mechanical behaviors and physiological responses of such biological structures, we develop an analytical model to quantify surface effects on the deformation of a coated cylindrical compressible liquid inclusion in an elastic matrix subjected to remote loading. Our analytical solution reveals that coating can either amplify or attenuate the volumetric strain of the inclusion, depending on the relative elastic moduli of inclusion, coating, and matrix. For illustration, we utilize this solution to explore amplification/attenuation of volumetric strain in musculoskeletal systems, nerve cells, and vascular tissues. We demonstrate that coating often plays a crucial role in mechanical regulation of the development and repair of human tissues and cells. Our model provides qualitative analysis of cross-scale mechanical response of coated liquid inclusions, helpful for constructing mechanical microenvironment of cells., (© 2024 IOP Publishing Ltd.)

Porous materials with sound absorption and load-bearing capabilities are in demand in engineering fields like aviation and rail transportation. However, achieving both properties simultaneously is challenging due to the trade-off between interconnected pores for sound absorption and mechanical strength. Inspired by quilling art, a novel design using spiral material formed by rolling planar materials into helical structures is proposed. Experimental results show high structural strength through self-locking mechanisms, while double porosities from interlayer spiral slits and aligned submillimeter pores provide excellent sound absorption. These spiral sheets surpass foam aluminum in specific strength (up to 5.1 MPa) and approach aerogels in sound absorption (average coefficient of 0.93 within 0-6400 Hz). With its adaptability to various planar materials, this spiral design allows for hybrid combinations of different materials for multi-functionality, paving the way for designing advanced, lightweight porous materials for broad applications., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Liquid-filled capillary tubes are a kind of standard component in life science (e.g., blood vessels, interstitial pores, and plant vessels) and engineering (e.g., MEMS microchannel resonators, heat pipe wicks, and water-saturated soils). Under sufficiently low temperatures, the liquid in a capillary tube undergoes phase transition, forming an ice nucleus randomly on its inner wall. However, how an ice layer forms from the nucleus and then expands, either axially or radially to the tube inner wall, remains obscure. We demonstrated, both experimentally and theoretically, that axial freezing along the inner wall of a water-filled capillary tube occurs way ahead of radial freezing, at a nearly constant velocity 3 orders in magnitude faster than the latter. Rapid release of latent heat during axial freezing was identified as the determining factor for the short duration of recalescence, resulting in an exponential rise of the supercooling temperature from ice nucleation via axial freezing to radial freezing. The profile of the ice-water interface is strongly dependent upon the length-to-radius ratio of the capillary tube and the supercooling degree at ice nucleation. The results obtained in this study bridge the knowledge gap between the classical nucleation theory and the Stefan solution of phase transition.

Purple Pennisetum ( Pennisetum purpureum Schumach), a hybrid between Taihucao No. 2 and the local wild species of purple Pennisetum , has dark red stems and leaves due to its anthocyanin content. This study explores the potential of purple napiergrass extracts (PNE) in alleviating obesity and metabolic disorders induced by a high-fat diet in mice, where 50% of the caloric content is derived from fat. Mice were orally administered low-dose or high-dose PNE alongside a high-fat diet. Experimental findings indicate that PNE attenuated weight gain, reduced liver, and adipose tissue weight, and lowered blood cholesterol, triglyceride, low-density lipoprotein, and blood sugar levels. Stained sections showed that PNE inhibited lipid accumulation and fat hypertrophy in the liver. Immunoblotting analysis suggested that PNE improved the inflammatory response associated with obesity, dyslipidemia, and hyperglycemia induced by a high-fat diet. Furthermore, PNE potentially functions as a PPAR-γ agonist, increasing the adiponectin (ADIPOQ) concentration and suppressing inflammatory factors, while elevating the anti-inflammatory factor interleukin-10 (IL-10) in the liver. PNE-treated mice showed enhanced activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and AMP-activated protein kinase (AMPK) pathways and increased fatty acid oxidation and liver lipolysis. In conclusion, this study elucidated the mechanisms underlying the anti-inflammatory, PI3K/Akt, and AMPK pathways in a high-fat diet-induced obesity model. These findings highlight the potential of PNE in reducing weight, inhibiting inflammation, and improving blood sugar and lipid levels, showing the potential for addressing obesity-related metabolic disorders in humans.

Dynamically evolving adhesions between cells and extracellular matrix (ECM) transmit time-varying signals that control cytoskeletal dynamics and cell fate. Dynamic cell adhesion and ECM stiffness regulate cellular mechanosensing cooperatively, but it has not previously been possible to characterize their individual effects because of challenges with controlling these factors independently. Therefore, a DNA-driven molecular system is developed wherein the integrin-binding ligand RGD can be reversibly presented and removed to achieve cyclic cell attachment/detachment on substrates of defined stiffness. Using this culture system, it is discovered that cyclic adhesion accelerates F-actin kinetics and nuclear mechanosensing in human mesenchymal stem cells (hMSCs), with the result that hysteresis can completely change how hMSCs transduce ECM stiffness. Results are dramatically different from well-known results for mechanotransduction on static substrates, but are consistent with a mathematical model of F-actin fragments retaining structure following loss of integrin ligation and participating in subsequent repolymerization. These findings suggest that cyclic integrin-mediated adhesion alters the mechanosensing of ECM stiffness by hMSCs through transient, hysteretic memory that is stored in F-actin., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Three-spot seahorse ( Hippocampus trimaculatus ) has been consumed as traditional Chinese medicine in Asian society. This study was designed to analyze the bioactive compounds of the solvent extracts from cultured three-spot seahorse by high pressure liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI/MS/MS). Subsequently, their biological activities were evaluated and confirmed by cell modes and Western blot analysis. Experimental results indicated that taurine and arginine were the primary bioactive compounds identified and quantified without pre- or post-column derivatization within 20 min retention time. The analytical method was established and validated with intraday/interday RSD from 0.25% to 3.34% and with recovery from 87.8% to 91.2%. As compared to other extracts, water layer extract (WLE) contained the most taurine and arginine contents of 6.807 and 0.437 mg/g (dry basis), respectively. In the meanwhile, WLE also showed anti-inflammatory activity on LPS-induced NO production and inhibited the protein expression of TNF-α and COX-2 by Western blot analysis with better cell viability., Competing Interests: The authors hereby declare that there are no conflicts of interest., (© 2023 The Authors. Food Science & Nutrition published by Wiley Periodicals LLC.)

Inspired by material hybrid design, novel hybrid sandwich shells were developed by filling a corrugated cylindrical structure with aluminum foam to achieve higher energy absorption performance. The crushing behavior of the foam-filled corrugated sandwich cylindrical shells (FFCSCSs) was investigated using theoretical and numerical methods. Numerical results revealed a significant enhancement in the energy absorption of FFCSCSs under axial compression, showcasing a maximum specific energy absorption of 60 kJ/kg. The coupling strengthening effect is highly pronounced, with a maximum value of F¯c/F¯ reaching up to 40%. The mechanism underlying this phenomenon can be approached from two perspectives. Firstly, the intrusion of folds into the foam insertions allows for more effective foam compression, maximizing its energy absorption capacity. Secondly, foam causes the folds to bend upwards, intensifying the mutual compression between the folds. This coupling mechanism was further investigated with a focus on analyzing the influence of parameters such as the relative density of the foam, the wall thickness of the sandwich shell, and the material properties. Moreover, a theoretical model was developed to accurately predict the mean crushing force of the FFCSCSs. Based on this model, the influence of various variables on the crushing behavior of the structure was thoroughly investigated through parametric studies.

China has implemented a series of long-term measures to control the spread of COVID-19, however, the effects of these measures on other chronic and acute respiratory infectious diseases remain unclear. Tuberculosis (TB) and scarlet fever (SF) serve as representatives of chronic and acute respiratory infectious diseases, respectively. In China's Guizhou province, an area with a high prevalence of TB and SF, approximately 40,000 TB cases and hundreds of SF cases are reported annually. To assess the impact of COVID-19 prevention and control on TB and SF in Guizhou, the exponential smoothing method was employed to establish a prediction model for analyzing the influence of COVID-19 prevention and control on the number of TB and SF cases. Additionally, spatial aggregation analysis was utilized to describe spatial changes in TB and SF before and after the COVID-19 outbreak. The parameters of the TB and SF prediction models are R 2  = 0.856, BIC = 10.972 and R 2  = 0.714, BIC = 5.325, respectively. TB and SF cases declined rapidly at the onset of COVID-19 prevention and control measures, with the number of SF cases decreasing for about 3-6 months and the number of TB cases remaining in decline for 7 months after the 11th month. The spatial aggregation of TB and SF did not change significantly before and after the COVID-19 outbreak but exhibited a marked decrease. These findings suggest that China's COVID-19 prevention and control measures also reduced the prevalence of TB and SF in Guizhou. These measures may have a long-term positive impact on TB, but a short-term effect on SF. Areas with high TB prevalence may continue to experience a decline due to the implementation of COVID-19 preventive measures in the future., (© 2023. The Author(s).)

Thin structural elements such as large-scale covering plates of aerospace protection structures and vertical stabilizers of aircraft are strongly influenced by gravity (and/or acceleration); thus, exploring how the mechanical behaviors of such structures are affected by gravitational field is necessary. Built upon a zigzag displacement model, this study establishes a three-dimensional vibration theory for ultralight cellular-cored sandwich plates subjected to linearly varying in-plane distributed loads (due to, e.g., hyper gravity or acceleration), with the cross-section rotation angle induced by face sheet shearing accounted for. For selected boundary conditions, the theory enables quantifying the influence of core type (e.g., close-celled metal foams, triangular corrugated metal plates, and metal hexagonal honeycombs) on fundamental frequencies of the sandwich plates. For validation, three-dimensional finite element simulations are carried out, with good agreement achieved between theoretical predictions and simulation results. The validated theory is subsequently employed to evaluate how the geometric parameters of metal sandwich core and the mixture of metal cores and composite face sheets influence the fundamental frequencies. Triangular corrugated sandwich plate possesses the highest fundamental frequency, irrespective of boundary conditions. For each type of sandwich plate considered, the presence of in-plane distributed loads significantly affects its fundamental frequencies and modal shapes.

Objective: We described epidemiological characteristics of pulmonary tuberculosis (PTB) among students and evaluated susceptible populations and areas in Guizhou province and also to provide scientific suggestions for prevention and control., Setting: Guizhou, China., Design: This is a retrospective epidemiological study on PTB in students., Methods: Data are from the China Information System for Disease Control and Prevention. We collected all PTB cases among the student population from 2010 to 2020 in Guizhou. Incidence, composition ratio and hotspot analysis were used to describe epidemiological and some clinical characteristics., Results: A total of 37 147 new student PTB cases were registered among the population aged 5-30 years during 2010-2020. The proportions of men and women were 53.71% and 46.29%, respectively. Cases aged 15-19 years dominated (63.91%), and the proportion of ethnic groups was increasing during the period. Generally, the raw annual incidence of PTB among the population was increasing from 32.585 per 100 000 persons in 2010 to 48.872 per 100 000 persons in 2020 ( c 2 trend =1283.230, p<0.001). March and April were the peak months of a year, and cases were clearly grouped in Bijie city. New cases were mainly identified via physical examination, and cases from active screening were still low (0.76%). Additionally, secondary PTB accounted for 93.68%, positive rate of pathogen was only 23.06%, and the recovery rate was 94.60%., Conclusions: The population aged 15-19 years is the vulnerable population, and Bijie city is the susceptible area. BCG vaccination and promotion for active screening should be the priority of futural PTB prevention and control. Tuberculosis laboratory capacity should be improved., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Glycolysis is a glucose metabolism pathway that generates the high-energy compound adenosine triphosphate, which supports cancer cell growth. Phosphofructokinase platelet (PFKP) plays a crucial role in glycolysis regulation and is involved in human cancer progression. However, the biological function of PFKP remains unclear in colorectal cancer (CRC). Methods: We analyzed the expression levels of PFKF in colon cancer cells and clinical samples using real-time PCR and western blot techniques. To determine the clinical significance of PFKP expression in colorectal cancer (CRC), we analyzed public databases. In addition, we conducted in vitro assays to investigate the effects of PFKP on cell growth, cell cycle, and motility. Results: An analysis by the Cancer Genome Atlas database revealed that PFKP was significantly overexpressed in CRC. We examined the levels of PFKP mRNA and protein, revealing that PFKP expression was significantly increased in CRC. The results of the univariate Cox regression analysis showed that high PFKP expression was linked to worse disease-specific survival (DSS) and overall survival (OS) [DSS: crude hazard ratio (CHR) = 1.84, 95% confidence interval (CI): 1.01-3.36, p = 0.047; OS: CHR=1.91, 95% CI: 1.06-3.43, p = 0.031]. Multivariate Cox regression analysis revealed that high PFKP expression was an independent prognostic biomarker for the DSS and OS of patients with CRC (DSS: adjusted HR = 2.07, 95% CI: 1.13-3.79, p = 0.018; AHR = 2.34, 95% CI: 1.29-4.25, p = 0.005). PFKP knockdown reduced the proliferation, colony formation, and invasion of CRC cells. In addition, the knockdown induced cell cycle arrest at the G0/G1 phase by impairing cell cycle-related protein expression. Conclusion: Overexpression of PFKP contributes to the growth and invasion of CRC by regulating cell cycle progression. PFKP expression can serve as a valuable molecular biomarker for cancer prognosis and a potential therapeutic target for treating CRC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Mechanotherapy is proposed as a new option for cancer treatment. Increasing evidence suggests that characteristic differences are present in the nuclear mechanics and mechanotransduction of cancer cells compared with those of normal cells. Recent advances in understanding nuclear mechanics and mechanotransduction provide not only further insights into the process of malignant transformation but also useful references for developing new therapeutic approaches. Herein, we present an overview of the alterations of nuclear mechanics and mechanotransduction in cancer cells and highlight their implications in cancer mechanotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Spirulina (Arthrospira maxima) hot water extracts such as calcium spirulan (Ca-SP) have demonstrated antiviral effects against herpes simplex virus (HSV), human immunodeficiency virus-1 (HIV-1), and influenza virus infections. There is no prior evidence suggesting the anti-viral activity of the spirulina hot water extract against respiratory syncytial virus (RSV)., Purpose: There are currently no effective antivirals available to treat RSV infection. Therefore, the development of safe and novel anti-RSV drugs is urgent and necessary. The aim of this work was to demonstrate the anti-RSV activity of spirulina hot water extracts and determine the potential mechanism of action., Methods: Cytotoxicity and anti-RSV activity of spirulina hot water extracts were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and neutralization assays, respectively. Potential mechanisms and components were assessed using time of addition, attachment, internalization, pull-down assays, and composition analysis., Results: The polysaccharide-enriched high-molecular weight fraction (>100 kDa, SHD1) had a high total sugar content, with rhamnose accounting for approximately 60 mol% of total monosaccharides. The main glycosyl linkages included 3-, 4-, and 2,3-rhamnopyranosyl linkages. All spirulina hot water extracts showed no toxicity toward human epithelial type 2 (HEp-2) cells but demonstrated anti-RSV activity. The SHD1 had a half maximal effective concentration (EC 50 ) of 0.0915 mg/ml and a selective index (SI) of >261.5 against RSV. SHD1 significantly reduced viral yield in a dose-dependent manner during the RSV attachment stage. SHD1 disrupted RSV internalization and inhibited RSV attachment (G) protein binding to heparan sulfate receptors on the host cell surface, thus preventing RSV attachment and entry., Conclusion: SHD1 serves as an effective candidate for novel drug development against RSV infection., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022. Published by Elsevier GmbH.)

Objective: In order to figure out the cause for two consecutive fetuses with nonimmune hydrops fetalis (NIHF) in a Taiwanese couple, whole-Exome Sequencing and Sanger Sequencing were applied for the family., Case Report: The two fetuses developed NIHF at gestation age of 19 and 21 weeks, respectively. The clinical features included ascites and pleural effusion, flattened nasofrontal angle, skin edema, clenched hands, ambiguous genitalia, hepatosplenomegaly and fetal thrombocytopenia. Magnetic resonance imaging of the brain showed cerebellar hypoplasia and delayed cortical maturation. The GBA deleterious variants c.1505+5G > C and c.308-1G > A were both detected in the two fetuses., Conclusion: The report provided the precious experience of the clinical presentation of perinatal lethal Gaucher disease (PLGD) and advice on reproductive medicine for the next pregnancy in a couple. The novel genetic mutations identified in the study also contribute to the known spectrum of PLGD-related mutations., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2023. Published by Elsevier B.V.)

Brain tissue is considered to be biphasic, with approximately 80% liquid and 20% solid matrix, thus exhibiting viscoelasticity due to rearrangement of the solid matrix and poroelasticity due to fluid migration within the solid matrix. However, how to distinguish poroelastic and viscoelastic effects in brain tissue remains challenging. In this study, we proposed a method of unconfined compression-isometric hold to measure the force versus time relaxation curves of porcine brain tissue samples with systematically varied sample lengths. Upon scaling the measured relaxation force and relaxation time with different length-dependent physical quantities, we successfully distinguished the poroelasticity and viscoelasticity of the brain tissue. We demonstrated that during isometric hold, viscoelastic relaxation dominated the mechanical behavior of brain tissue in the short-time regime, while poroelastic relaxation dominated in the long-time regime. Furthermore, compared with poroelastic relaxation, viscoelastic relaxation was found to play a more dominant role in the mechanical response of porcine brain tissue. We then evaluated the differences between poroelastic and viscoelastic effects for both porcine and human brain tissue. Because of the draining of pore fluid, the Young's moduli in poroelastic relaxation were lower than those in viscoelastic relaxation; brain tissue changed from incompressible during viscoelastic relaxation to compressible during poroelastic relaxation, resulting in reduced Poisson ratios. This study provides new insights into the physical mechanisms underlying the roles of viscoelasticity and poroelasticity in brain tissue. STATEMENT OF SIGNIFICANCE: Although the poroviscoelastic model had been proposed to characterize brain tissue mechanical behavior, it is difficult to distinguish the poroelastic and viscoelastic behaviors of brain tissue. The study distinguished viscoelasticity and poroelasticity of brain tissue with time scales and then evaluated the differences between poroelastic and viscoelastic effects for both porcine and human brain tissue, which helps to accurate selection of constitutive models suitable for application in certain situations (e.g., pore-dominant and viscoelastic-dominant deformation)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

During mesenchymal development, the sources of mechanical forces transduced by cells transition over time from predominantly cell-cell interactions to predominantly cell-extracellular matrix (ECM) interactions. Transduction of the associated mechanical signals is critical for development, but how these signals converge to regulate human mesenchymal stem cells (hMSCs) mechanosensing is not fully understood, in part because time-evolving mechanical signals cannot readily be presented in vitro. Here, we established a DNA-driven cell culture platform that could be programmed to present the RGD peptide from fibronectin, mimicking cell-ECM interactions, and the HAVDI peptide from N-cadherin, mimicking cell-cell interactions, through DNA hybridization and toehold-mediated strand displacement reactions. The platform could be programmed to mimic the evolving cell-ECM and cell-cell interactions during mesenchymal development. We applied this platform to reveal that RGD/integrin ligation promoted cofilin phosphorylation, while HAVDI/N-cadherin ligation inhibited cofilin phosphorylation. Cofilin phosphorylation upregulated perinuclear apical actin fibers, which deformed the nucleus and thereby induced YAP nuclear localization in hMSCs, resulting in subsequent osteogenic differentiation. Our programmable culture platform is broadly applicable to the study of dynamic, integrated mechanobiological signals in development, healing, and tissue engineering., (© 2022. The Author(s).)

Blockage of ureter caused by kidney stone, accompanied by severe pain/infections, is a high incidence urinary tract disease that has received extensive attention. Currently, in clinics, a kidney stone with diameter less than ∼5 mm is considered capable of passing through ureter. However, this critical size (∼5 mm) is empirically based, lacking quantitative analysis. In this study, we proposed a stone-ureter interaction model to quantificationally estimate the critical size of kidney stone passing through ureter. We revealed that the critical size of kidney stone is related to ureter size, about 11%-22% larger than the inner diameter of ureter. Further, based upon the Winkler elastic foundation beam model, we developed a simplified stone-ureter interaction model to evaluate how this critical size is dependent upon the stiffness of ureter and the surface roughness of kidney stone. The proposed model may help urologists improve the accuracy of personalized diagnosis and treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Acoustic transduction by plants has been proposed as a mechanism to enable just-in-time up-regulation of metabolically expensive defensive compounds. Although the mechanisms by which this "hearing" occurs are unknown, mechanosensation by elongated plant hair cells known as trichomes is suspected. To evaluate this possibility, we developed a theoretical model to evaluate the acoustic radiation force that an elongated cylinder can receive in response to sounds emitted by animals, including insect herbivores, and applied it to the long, cylindrical stem trichomes of the tomato plant Solanum lycopersicum. Based on perturbation theory and validated by finite element simulations, the model quantifies the effects of viscosity and frequency on this acoustic radiation force. Results suggest that acoustic emissions from certain animals, including insect herbivores, may produce acoustic radiation force sufficient to trigger stretch-activated ion channels., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Galacto-oligosaccharides (GOS) are important prebiotic supplements for commercial nutraceutical food. The prebiotic efficacy of functional GOS is dependent on their chemical profile. Screening potential markers aids specifications and quality control of GOS materials. However, profiling analysis of GOS with a degree of polymerization (DP) ≥ 4 is still challenging. This study presents a porous graphitic carbon liquid chromatography-orbitrap tandem mass spectrometry-based method that characterized 58 linear and 10 branched GOS and detected 59 non-reducing GOS from DP2 to DP6. The results indicated that 15 major group components with DP2-DP5 accounted for more than 65% of total GOS content in GOS samples, while non-reducing GOS components accounted for only 2.8-7.6%. Substantial variations in components occurred in samples from different batches and sources. Structural and constitutive diversity were dominated by DP3-DP5. This method can help control the quality of GOS products and be used to investigate the structural and prebiotic-efficacy relationships., (Copyright © 2022. Published by Elsevier Ltd.)

Some clinically used anti-cancer drugs are obtained from natural products. Allyl isothiocyanate (AITC), a plant-derived compound abundant in cruciferous vegetables, has been shown to possess an anti-cancer ability in human cancer cell lines in vitro, including human brain glioma cells. However, the anti-cancer effects of AITC in human glioblastoma (GBM) cells in vivo have not yet been examined. In the present study, we used GBM8401/ luc2 human glioblastoma cells and a GBM8401/ luc2 -cell-bearing animal model to identify the treatment efficacy of AITC. Here, we confirm that AITC reduced total cell viability and induced cell apoptosis in GBM8401/ luc2 cells in vitro. Furthermore, Western blotting also showed that AITC induced apoptotic cell death through decreased the anti-apoptotic protein BCL-2, MCL-1 expression, increased the pro-apoptotic protein BAX expression, and promoted the activities of caspase-3, -8, and -9. Therefore, we further investigated the anti-tumor effects of AITC on human GBM8401/ luc2 cell xenograft mice. The human glioblastoma GBM8401/ luc2 cancer cells were subcutaneously injected into the right flank of BALB/c nude mice to generate glioblastoma xenograft mice. The animals were randomly divided into three groups: group I was treated without AITC (control); group II with 0.1 mg/day of AITC; and group III with 0.2 mg/day of AITC every 3 days for 27 days. Bodyweight, and tumor volume (size) were recorded every 3 days. Tumors exhibiting Luc2 intensity were measured, and we quantified intensity using Living Image software on days 0, 12, and 24. After treatment, tumor weight from each mouse was recorded. Tumor tissues were examined for histopathological changes using H&E staining, and we analyzed the protein levels via immunohistochemical analysis. Our results indicate that AITC significantly inhibited tumor growth at both doses of AITC due to the reduction in tumor size and weight. H&E histopathology analysis of heart, liver, spleen, and kidney samples revealed that AITC did not significantly induce toxicity. Body weight did not show significant changes in any experiment group. AITC significantly downregulated the protein expression levels of MCL-1, XIAP, MMP-9, and VEGF; however, it increased apoptosis-associated proteins, such as cleaved caspase-3, -8, and -9, in the tumor tissues compared with the control group. Based on these observations, AITC exhibits potent anti-cancer activity in the human glioblastoma cell xenograft model via inhibiting tumor cell proliferation and the induction of cell apoptosis. AITC may be a potential anti-GBM cancer drug that could be used in the future.

How cells sense tissue stiffness to guide cell migration is a fundamental question in development, fibrosis and cancer. Although durotaxis-cell migration towards increasing substrate stiffness-is well established, it remains unknown whether individual cells can migrate towards softer environments. Here, using microfabricated stiffness gradients, we describe the directed migration of U-251MG glioma cells towards less stiff regions. This 'negative durotaxis' does not coincide with changes in canonical mechanosensitive signalling or actomyosin contractility. Instead, as predicted by the motor-clutch-based model, migration occurs towards areas of 'optimal stiffness', where cells can generate maximal traction. In agreement with this model, negative durotaxis is selectively disrupted and even reversed by the partial inhibition of actomyosin contractility. Conversely, positive durotaxis can be switched to negative by lowering the optimal stiffness by the downregulation of talin-a key clutch component. Our results identify the molecular mechanism driving context-dependent positive or negative durotaxis, determined by a cell's contractile and adhesive machinery., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

During descent, a single-winged maple seed (samara) can naturally reach a delicate equilibrium state, stable autorotation, before landing. This article reveals the intrinsic equilibrium of a particular type of samaras in terms of measurable aerodynamic and geometric parameters. To this end, we conducted a series of in situ measurements for the rate of vertical descent (exclusive of crosswind) of an autorotating samara in a natural range of samara sizes and masses. We then extended the range of size and mass by introducing artificial samaras, with discrete mass elements purposely designed to approximate the asymmetrical and nonuniform distribution of mass found with natural samaras. Based on the widened range, a fundamental nondimensional correlation of dynamic pressure and disc loading was generalized, where all stable autorotation descent profiles collapse to a single descent characteristic curve, irrespective of the size and mass of the natural and artificial samara's specimens. Results reveal that for stably autorotating (both natural and artificial) samaras, their terminal descent velocity (expressed as dynamic pressure) and disc loading attained equilibrium at a value that is inversely proportional to the coefficient of lift.

Purpose of Review: To review emerging treatments for thyroid eye disease (TED) associated extraocular muscle myopathy and dysthyroid optic neuropathy (DON)., Recent Findings: Emerging targeted biologic therapies may alter the disease course in TED. Teprotumumab, a type I insulin-like growth factor receptor inhibitor, is the most recent addition to the treatments available for TED-associated extraocular muscle myopathy causing diplopia. Small studies also suggest a potential therapeutic benefit for DON. Various recent studies have also expanded our knowledge on conventional TED therapies. The therapeutic landscape of TED and its sequelae has evolved in recent years. New targeted therapies have the potential to reduce the extraocular muscle and orbital volume expansion which can lead to diplopia and vision loss from optic nerve compression. Longer term efficacy and durability data is needed to determine the role biologics, such as teprotumumab, should play in the treatment of TED patients compared to the current standard of care., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Upper and lower blepharoplasty are among the most common procedures in aesthetic surgery and are often emotionally laden due to the subjective nature of outcomes and implications with beauty and self-identity. This article capitalizes on the increasing wealth of patient-provided health information online and is the first to analyze the emotions surrounding blepharoplasty discussions in an open internet health forum, MedHelp., Methods: We used Python to scrape MedHelp for threads that contained "blepharoplasty" and then used IBM Watson Natural Language Understanding to perform sentiment analyses, calculating a general sentiment score (-1 to +1) as well as emotion scores for anger, sadness, joy, fear, and disgust (0 to 1) for posts and keywords contained within the posts. Keywords were then manually grouped into five distinct clinical categories: symptoms, doctor, treatment, medication, and body., Results: We collected 52 threads containing "blepharoplasty," yielding 154 posts and 1365 keywords. The average sentiment score was negative among all posts (-0.15) and keywords (-0.30). Among all posts and keywords, sadness had the highest score and disgust had the lowest score., Conclusions: Fear and sadness are the predominant emotions for blepharoplasty patients online, and the most negative symptoms cited are not ones that surgeons typically expect., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Phenethyl isothiocyanate (PEITC), extracted from cruciferous vegetables, showed anticancer activity in many human cancer cells. Our previous studies disclosed the anticancer activity of PEITC in human glioblastoma multiforme (GBM) 8401 cells, including suppressing the cell proliferation, inducing apoptotic cell death, and suppressing cell migration and invasion. Furthermore, PEITC also inhibited the growth of xenograft tumors of human glioblastoma cells. We are the first to investigate PEITC effects on the receptor tyrosine kinase (RTK) signaling pathway and the effects of proinflammatory cytokines on glioblastoma. The cell viability was analyzed by flow cytometric assay. The protein levels and mRNA expressions of cytokines, including tumor necrosis factor- α (TNF- α ), interleukin-1 β (IL-1 β ), and interleukin-6 (IL-6), were determined by enzyme-linked immunosorbent assay (ELISA) reader and real-time polymerase chain reaction (PCR) analysis, respectively. Furthermore, nuclear factor-kappa B- (NF- κ B-) associated proteins were evaluated by western blotting. NF- κ B expression and nuclear translocation were confirmed by confocal laser microscopy. NF- κ B binding to the DNA was examined by electrophoretic mobility shift assay (EMSA). Our results indicated that PEITC decreased the cell viability and inhibited the protein levels and expressions of IL-1 β , IL-6, and TNF- α genes at the transcriptional level in GBM 8401 cells. PEITC inhibited the binding of NF- κ B on promoter site of DNA in GBM 8401 cells. PEITC also altered the protein expressions of protein kinase B (Akt), extracellular signal-regulated kinase (ERK), and NF- κ B signaling pathways. The inflammatory responses in human glioblastoma cells may be suppressed by PEITC through the phosphoinositide 3-kinase (PI3K)/Akt/NF- κ B signaling pathway. Thus, PEITC may have the potential to be an anti-inflammatory agent for human glioblastoma in the future., Competing Interests: The authors declare no conflicts of interest in this work., (Copyright © 2022 Sheng-Yao Hsu et al.)

Long noncoding RNAs play a key role in the progression of colorectal cancer (CRC). However, the role and mechanism of LOC550643 in CRC cell growth and metastasis remain largely unknown. In this study, we assessed the clinical impacts of LOC550643 on CRC through the analysis of The Cancer Genome Atlas database, which revealed the significant upregulation of LOC550643 in CRC. Moreover, the high expression of LOC550643 was associated with poor survival in patients with CRC ( p = 0.001). Multivariate Cox regression analysis indicated that LOC550643 overexpression was an independent prognostic factor for shorter overall survival in patients with CRC (adjusted hazard ratio, 1.90; 95% confidence interval, 1.21-3.00; p = 0.006). A biological function analysis revealed that LOC550643 knockdown reduced colon cancer cell growth by hindering cell cycle progression. In addition, LOC550643 knockdown significantly induced cell apoptosis through the inhibition of signaling activity in phosphoinositide 3-kinases. Moreover, LOC550643 knockdown contributed to the inhibition of migration and invasion ability in colon cancer cells. Furthermore, miR-29b-2-5p interacted with the LOC550643 sequence. Ectopic miR-29b-2-5p significantly suppressed colon cancer cell growth and motility and induced cell apoptosis. Our findings suggest that, LOC550643-miR-29b-2-5p axis was determined to participate in the growth and metastasis of colon cancer cells; this could serve as a useful molecular biomarker for cancer diagnosis and as a potential therapeutic target for CRC.

A novel non-C 2 -symmetric bis -benzimidazolium salt derived from (±)-valinol has been prepared by a simple and straightforward process in good yield. The structure of bis -benzimidazolium salt provided a bulky steric group on the ethylene bridge; which facilitates the catalytic efficacy in the C( sp 2 )-C( sp 2 ) formation. Its catalytic activity in Suzuki-Miyaura cross-coupling reaction of unactivated aryl chlorides has been found to have high efficacy in 1 mol% Pd loading. This protocol demonstrated the potential on the synthesis of sterically hindered biaryls.

Tazarotene-induced gene 1 (TIG1) is considered to be a tumor suppressor gene that is highly expressed in normal or well-differentiated colon tissues, while downregulation of TIG1 expression occurs in poorly differentiated colorectal cancer (CRC) tissues. However, it is still unclear how TIG1 regulates the tumorigenesis of CRC. Polo-like kinases (Plks) are believed to play an important role in regulating the cell cycle. The performance of PLK2 in CRC is negatively correlated with the differentiation status of CRC tissues. Here, we found that PLK2 can induce the growth of CRC cells and that TIG1 can prevent PLK2 from promoting the proliferation of CRC cells. We also found that the expression of PLK2 in CRC cells was associated with low levels of Fbxw7 protein and increased expression of cyclin E1. When TIG1 was coexpressed with PLK2, the changes in Fbxw7/cyclin E1 levels induced by PLK2 were reversed. In contrast, silencing TIG1 promoted the proliferation of CRC, and when PLK2 was also silenced, the proliferation of CRC cells induced by TIG1 silencing was significantly inhibited. The above research results suggest that TIG1 can regulate the tumorigenesis of CRC by regulating the activity of PLK2., (© 2021 International Federation for Cell Biology.)

Background: This study aims to assess the association between age and outcomes in patients undergoing hemorrhoidectomy., Methods: This is a population-based cohort study. A retrospectively collected database with consecutive patients whose symptomatic prolapsed hemorrhoids managed by the LigaSure hemorrhoidectomy between Jan. 2015 and May 2017 was reviewed. Among 1238 patients, 1075 were under 65 years old (group 1), and 163 were 65 years old or older (group 2). Both groups were compared regarding baseline characteristics and surgical outcomes., Results: All patients tolerated the whole course of the operation in the prone jackknife position without anesthetic-associated complications. There was no significant difference between these two groups regarding sex, hemorrhoids grade, operation time, duration of hospital stays, postoperative pain score, analgesic consumption, total postoperative complications, re-admission rate, reoperation rate and follow-up times. The multivariate logistic regression analysis that may contribute to postoperative complications revealed no significant difference for all complications between both groups., Conclusion: The LigaSure hemorrhoidectomy for elderly patients is safe and effective without significant difference in short-term operative outcomes and all complication rates, compared with younger patients., (© 2021. The Author(s).)

Mesenchymal stem cells adopt differentiation pathways based upon cumulative effects of mechanosensing. A cell's mechanical microenvironment changes substantially over the course of development, beginning from the early stages in which cells are typically surrounded by other cells and continuing through later stages in which cells are typically surrounded by extracellular matrix. How cells erase the memory of some of these mechanical microenvironments while locking in memory of others is unknown. Here, we develop a material and culture system for modifying and measuring the degree to which cells retain cumulative effects of mechanosensing. Using this system, we discover that effects of the RGD adhesive motif of fibronectin (representative of extracellular matrix), known to impart what is often termed "mechanical memory" in mesenchymal stem cells via nuclear YAP localization, are erased by the HAVDI adhesive motif of the N-cadherin (representative of cell-cell contacts). These effects can be explained by a motor clutch model that relates cellular traction force, nuclear deformation, and resulting nuclear YAP re-localization. Results demonstrate that controlled storage and removal of proteins associated with mechanical memory in mesenchymal stem cells is possible through defined and programmable material systems., (© 2021. The Author(s).)

Although coupling between cardiomyocytes and myofibroblasts is well known to affect the physiology and pathophysiology of cardiac tissues across species, relating these observations to humans is challenging because the effect of this coupling varies across species and because the sources of these effects are not known. To identify the sources of cross-species variation, we built upon previous mathematical models of myofibroblast electrophysiology and developed a mechanoelectrical model of cardiomyocyte-myofibroblast interactions as mediated by electrotonic coupling and transforming growth factor-β1. The model, as verified by experimental data from the literature, predicted that both electrotonic coupling and transforming growth factor-β1 interaction between myocytes and myofibroblast prolonged action potential in rat myocytes but shortened action potential in human myocytes. This variance could be explained by differences in the transient outward K + current associated with differential Kv4.2 gene expression across species. Results are useful for efforts to extrapolate the results of animal models to the predicted effects in humans and point to potential therapeutic targets for fibrotic cardiomyopathy., (Copyright © 2021 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Mechanical deformation of human skin provides essential information about human motions, muscle stretching, vocal fold vibration, and heart rates. Monitoring these activities requires the measurement of strains at different levels. Herein, we report a wearable wide-range strain sensor based on conducting polymer poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS). A bioinspired bilayer structure was constructed to enable a wide-range strain sensing (1%~100%). Besides, hydrogel was chosen as the biological- and mechanical-compatible interface layer with the human skin. Finally, we demonstrated that the strain sensor is capable of monitoring various strain-related activities, including subtle skin deformation (pulse and phonation), mid-level body stretch (swallowing and facial expressions), and substantial joint movement (elbow bending)., Competing Interests: Declaration of Interests The authros declare no competing interests.

Liquid-filled porous materials exist widely in nature and engineering fields, with the diffusion of substances in them playing an important role in system functions. Although surface evaporation is often inevitable in practical scenarios, the evaporation effects on diffusion behavior in liquid-filled porous materials have not been well explored yet. In this work, we performed noninvasive diffusion imaging experiments to observe the diffusion process of erioglaucine disodium salt dye in a liquid-filled nitrocellulose membrane under a wide range of relative humidities (RHs). We found that evaporation can significantly accelerate the diffusion rate and alter concentration distribution compared with the case without evaporation. We explained the accelerated diffusion phenomenon by the mechanism that evaporation would induce a weak flow in liquid-filled porous materials, which leads to convective diffusion, i.e. , evaporation-induced flow and diffusion (EIFD). Based on the EIFD mechanism, we proposed a convective diffusion model to quantitatively predict the diffusion process in liquid-filled porous materials under evaporation and experimentally validated the model. Introducing the dimensionless Peclet ( P e ) number to measure the relative contribution of the evaporation effect to pure molecular diffusion, we demonstrated that even at a high RH of 95%, where the evaporation effect is usually assumed negligible in common sense, the evaporation-induced diffusion still overwhelms the molecular diffusion. The flow velocity induced by evaporation in liquid-filled porous materials was found to be 0.4-5 μm/s, comparable to flow in many biological and biomedical systems. The present analysis may help to explain the driving mechanism of tissue perfusion and provide quantitative analysis or inspire new control methods of flow and material exchange in numerous cutting-edge technologies, such as paper-based diagnostics, hydrogel-based flexible electronics, evaporation-induced electricity generation, and seawater purification., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Familial hypercholesterolemia (FH) is a common genetic disorder characterized by a lifelong elevated low-density lipoprotein cholesterol (LDL-C) level. The relationship between FH and ischemic stroke is still controversial. We enrolled ischemic stroke patients prospectively in our neurological ward, and divided them into two groups according to LDL-C levels with a threshold of 130 mg/dl. Targeted sequencing was performed in all stroke patients for LDLR, APOB , and PCSK9 genes. The fifty-eight high-LDL subjects were older, prevalence of previous myocardial infarction/stroke history was lower, and the first stroke age was older compared with values in the sixty-three low-LDL cases. The prevalence of FH in Han-Chinese stroke patients was 5.0%, and was 10.3% in those with a higher LDL-C level. We identified six carriers, who had higher percentages of large vessel stroke subtype (66.7% vs. 15.4%) and transient ischemic attack (33.3% vs. 3.8%), previous myocardial infarction/stroke history (50.0% vs. 11.5%), statin use (50.0% vs. 11.5%), and increased carotid intima-media thickness (IMT) (0.9-1.2mm vs.0.7-9.0mm) compared with the other hypercholesterolemic patients without pathogenic variants. Ischemic stroke patients carrying FH pathogenic variants seemed to have a higher risk for large artery stroke and transient ischemic attack. The IMT exam could be useful to screen for FH in hypercholesterolemic stroke patients.

Hydrogels are commonly doped with stiff nanoscale fillers to endow them with the strength and stiffness needed for engineering applications. Although structure-property relations for many polymer matrix nanocomposites are well established, modeling the new generation of hydrogel nanocomposites requires the study of processing-structure-property relationships because subtle differences in chemical kinetics during their synthesis can cause nearly identical hydrogels to have dramatically different mechanical properties. The authors therefore assembled a framework to relate synthesis conditions (including hydrogel and nanofiller mechanical properties and light absorbance) to gelation kinetics and mechanical properties. They validated the model against experiments on a graphene oxide (GO) doped oligo (ethylene glycol) diacrylate (OEGDA), a system in which, in apparent violation of laws from continuum mechanics, doping can reduce rather than increase the stiffness of the resulting hydrogel nanocomposites. Both model and experiment showed a key role light absorbance-dominated gelation kinetics in determining nanocomposite mechanical properties in conjunction with nanofiller reinforcement, with the nanofiller's attenuation of chemical kinetics sometimes outweighing stiffening effects to explain the observed, anomalous loss of stiffness. By bridging the chemical kinetics and mechanics of nanocomposite hydrogels, the authors' modeling framework shows promise for broad applicability to design of hydrogel nanocomposites., (© 2021 Wiley-VCH GmbH.)

Background: Identifying patients with de novo acute myeloid leukemia (AML) who will probably respond to the "7 + 3" induction regimen remains an unsolved clinical challenge. This study aimed to identify whether c-Myc could facilitate cytogenetics to predict a "7 + 3" induction chemoresponse in de novo AML. Methods: We stratified 75 untreated patients (24 and 51 from prospective and retrospective cohorts, respectively) with de novo AML who completed "7 + 3" induction into groups with and without complete remission (CR). We then compared Myc-associated molecular signatures between the groups in the prospective cohort after gene set enrichment analysis. The expression of c-Myc protein was assessed by immunohistochemical staining. We defined high c-Myc-immunopositivity as > 40% of bone marrow myeloblasts being c-Myc (+). Results: Significantly more Myc gene expression was found in patients who did not achieve CR by "7 + 3" induction than those who did (2439.92 ± 1868.94 vs. 951.60 ± 780.68; p = 0.047). Expression of the Myc gene and c-Myc protein were positively correlated (r = 0.495; p = 0.014). Although the non-CR group did not express more c-Myc protein than the CR group (37.81 ± 25.13% vs. 29.04 ± 19.75%; p = 0.151), c-Myc-immunopositivity could be a surrogate to predict the "7 + 3" induction chemoresponse (specificity: 81.63%). More importantly, c-Myc-immunopositivity facilitated cytogenetics to predict a "7 + 3" induction chemoresponse by increasing specificity from 91.30 to 95.92%. Conclusion: The "7 + 3" induction remains the standard of care for de novo AML patients, especially for those without a high c-Myc-immunopositivity and high-risk cytogenetics. However, different regimens might be considered for patients with high c-Myc-immunopositivity or high-risk cytogenetics., Competing Interests: CT received an honorarium and consulting fees from Novartis, Roche, Takeda, Johnson and Johnson, Amgen, BMS Celgene, Kirin, AbbVie, and MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hsiao, Wang, Lu, Shih, Su, Tsai, Jhan, Lia, Chuang, Chang and Teng.)