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Acoustic signaling among birds is central to intra-species communication, courtship, and reproductive success, and so habitat suitability is partially dependent upon the availability of a suitable acoustic niche. It is well documented that birds may modify their vocal behavior to avoid overlap with anthropogenic noise pollution, but responses to biotic signal making are less well understood. This study uses more than 50,000 h of audio recorded in tropical forest, and machine learning methods for the detection of the vocalizations of nine species of bird and tymbalizations of three species of cicada to examine patterns of signal masking and co-chorusing avoidance among species pairs. Among these focal species, no bird avoided co-chorusing with any other bird. Birds avoided co-chorusing with cicadas only and always when (1) the bird vocalized in a frequency band completely overlapped by the cicada tymbalization, and (2) the cicada tymbalization saturated the majority of that frequency band. These results indicate that avian behavioral modifications in response to biotic noise in longstanding species communities is similar to behavioral modifications observed in populations subjected to high levels of anthropogenic noise pollution—in all cases overlap avoidance is species-specific and dependent upon both frequency and intensity. [ABSTRACT FROM AUTHOR]

Fluid dynamics computations for tube-like geometries are crucial in biomedical evaluations of vascular and airways fluid dynamics. Physics-Informed Neural Networks (PINNs) have emerged as a promising alternative to traditional computational fluid dynamics (CFD) methods. However, vanilla PINNs often demand longer training times than conventional CFD methods for each specific flow scenario, limiting their widespread use. To address this, multi-case PINN approach has been proposed, where varied geometry cases are parameterized and pre-trained on the PINN. This allows for quick generation of flow results in unseen geometries. In this study, we compare three network architectures to optimize the multi-case PINN through experiments on a series of idealized 2D stenotic tube flows. The evaluated architectures include the 'Mixed Network', treating case parameters as additional dimensions in the vanilla PINN architecture; the "Hypernetwork", incorporating case parameters into a side network that computes weights in the main PINN network; and the "Modes" network, where case parameters input into a side network contribute to the final output via an inner product, similar to DeepONet. Results confirm the viability of the multi-case parametric PINN approach, with the Modes network exhibiting superior performance in terms of accuracy, convergence efficiency, and computational speed. To further enhance the multi-case PINN, we explored two strategies. First, incorporating coordinate parameters relevant to tube geometry, such as distance to wall and centerline distance, as inputs to PINN, significantly enhanced accuracy and reduced computational burden. Second, the addition of extra loss terms, enforcing zero derivatives of existing physics constraints in the PINN (similar to gPINN), improved the performance of the Mixed Network and Hypernetwork, but not that of the Modes network. In conclusion, our work identified strategies crucial for future scaling up to 3D, wider geometry ranges, and additional flow conditions, ultimately aiming towards clinical utility. [ABSTRACT FROM AUTHOR]

The Weakly Compressible Smoothed Particle Hydrodynamics (WCSPH) has been applied to simulate the flow through a Gravitational Vertical Turbine (GVT) configuration and the motion of the turbine of a small hydropower system. The turbine blades are assumed to be rigid bodies moving with one-degree of freedom, which is the rotation about its shaft due the hydrodynamic forces of the flow. The intake flow is an open channel flow which falls into a cylindrical basin which houses the turbine and impinges on the turbine blades. The method of simulation is the Weakly Compressible Smoothed Hydrodynamics (WCSPH) with the turbulence models in the equations of motion and the boundary conditions. The results are compared with a laboratory experiments conducted for the same dimension and the configuration. The flow features agree well and the motion of the turbine with a representative mass and a load agrees reasonably with the laboratory experiments [ABSTRACT FROM AUTHOR]

Culture pH is very crucial to hydrogen production in the photo-fermentation process. Excessively low pH can directly affect cell growth and hydrogen production by changing bacterial physiological characteristics. Thus, screening acid-tolerant strains that can alleviate acid stress with enhanced hydrogen production is essential. In this work, an acid-tolerant mutant Rhodobacter capsulatus AT11 was isolated by transposon technology, and its photosynthetic characteristic under different initial pH values was investigated. The results indicated that the H2 yield of AT11 at initial pH of 5.5 was 4682.64 mL·L−1, which was 310.65% higher than that of wild strain JL1, and the mutant gene in AT11 was electron transfer flavoprotein (etf). Then an etf-deletion mutant JL1401 was constructed by deleting etf to verify the effect of etf on H2 production and investigate the acid-tolerance mechanism. Its H2 production at initial pH of 5.5 was significantly increased compared to its parental strain JL1. In addition, its photosynthetic characteristic with ammonium additives was studied. Under the condition of 1.8 mM ammonium, hydrogen production was still up to 2637.14 ± 41.46 mL·L−1, while hydrogen production of JL1 was inhibited. Cornstalk hydrolysate was used to evaluate the practical application of the constructed acid-tolerant mutant strains. The hydrogen yield reached 249.3 ± 16.8 mL-H2·g−1-cornstalk and 285.3 ± 19.1 mL-H2·g−1-cornstalk by R. capsulatus AT11 and JL1401, which were 2.9-fold and 3.3-fold compared to that of WT strain JL1, respectively. [ABSTRACT FROM AUTHOR]

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The calcium channels are the main pathogenesis and therapeutic target for post-traumatic epilepsy (PTE). However, differentially expressed miRNAs (DEMs) and mRNAs associated with calcium channels in PTE and their interactions are poorly understood. We produced a PTE model in rats and conducted RNA-seq in PTE rats. Gene annotation was used to verify differentially expressed mRNAs related to calcium channels. RNAhybrid, PITA, and Miranda prediction were used to build the miRNA–mRNA pairs. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used for the functional enrichment analysis of DEMs. The quantification changes of mRNA and miRNA were verified by RT-qPCR. There were 431 identified differentially expressed genes (DEGs) in PTE rats compared with the sham group, of which five mRNAs and 7 miRNAs were related to calcium channels. The miRNA–mRNA network suggested a negative correlation between 11 pairs of miRNA–mRNA involved in the p53 signaling pathway, HIF-1 signaling pathway. RT-qPCR verified three upregulated mRNAs in PTE rats, associated with 7 DEMs negatively related to them, respectively. This study has revealed the changes in miRNA–mRNA pairs associated with calcium channels in PTE, which might contribute to the further interpretation of potential underlying molecular mechanisms of PTE and the discovery of promising diagnostics. [ABSTRACT FROM AUTHOR]

Left ventricle myocardium has a complex micro-architecture, which was revealed to consist of myocyte bundles arranged in a series of laminar sheetlets. Recent imaging studies demonstrated that these sheetlets re-orientated and likely slided over each other during the deformations between systole and diastole, and that sheetlet dynamics were altered during cardiomyopathy. However, the biomechanical effect of sheetlet sliding is not well-understood, which is the focus here. We conducted finite element simulations of the left ventricle (LV) coupled with a windkessel lumped parameter model to study sheetlet sliding, based on cardiac MRI of a healthy human subject, and modifications to account for hypertrophic and dilated geometric changes during cardiomyopathy remodeling. We modeled sheetlet sliding as a reduced shear stiffness in the sheet-normal direction and observed that (1) the diastolic sheetlet orientations must depart from alignment with the LV wall plane in order for sheetlet sliding to have an effect on cardiac function, that (2) sheetlet sliding modestly aided cardiac function of the healthy and dilated hearts, in terms of ejection fraction, stroke volume, and systolic pressure generation, but its effects were amplified during hypertrophic cardiomyopathy and diminished during dilated cardiomyopathy due to both sheetlet angle configuration and geometry, and that (3) where sheetlet sliding aided cardiac function, it increased tissue stresses, particularly in the myofibre direction. We speculate that sheetlet sliding is a tissue architectural adaptation to allow easier deformations of the LV walls so that LV wall stiffness will not hinder function, and to provide a balance between function and tissue stresses. A limitation here is that sheetlet sliding is modeled as a simple reduction in shear stiffness, without consideration of micro-scale sheetlet mechanics and dynamics. [ABSTRACT FROM AUTHOR]

Existing therapies for type 2 diabetes mellitus (T2DM) show limited efficacy or have adverse effects. Numerous genetic variants associated with T2DM have been identified, but progress in translating these findings into potential drug targets has been limited. Here, we describe the tools and platforms available to identify effector genes from T2DM-associated coding and non-coding variants and prioritize them for functional studies. We discuss QSER1 and SLC12A8 as examples of genes that have been identified as possible T2DM candidate genes using these tools and platforms. We suggest further approaches, including the use of sequencing data with increased sample size and ethnic diversity, single-cell omics data for analyses, glycaemic trait associations to predict gene function and, potentially, human induced pluripotent stem cell 'village' cultures, to strengthen current gene functionalization workflows. Effective prioritization of T2DM-associated genes for experimental validation could expedite our understanding of the genetic mechanisms responsible for T2DM to facilitate the use of precision medicine in its treatment. More genetic variants associated with type 2 diabetes mellitus are being identified. This Perspective article outlines various tools and platforms that can be applied to prioritize candidate genes associated with an increased risk of disease for functional validation. [ABSTRACT FROM AUTHOR]

The high-pressure bypass valve stem of an ultra-supercritical unit has undergone a fatal fracture after running for more than 10,000 h. We analyzed the causes and types of the fracture by applying a series of tests: macroscopic and metallographic observation, chemical analysis, scanning electron microscopy (SEM), microhardness, and high-temperature tensile tests. The results show that the leading reasons for fracture are inadequate chemical composition of the material, unreasonable structural design, insufficient high-temperature strength, vibration, and corrosion. Furthermore, the two ends of the dowel hole represent the crack source, and crack propagation and transient fracture zones could be observed. Based on these characteristics, it is concluded that the fracture of the valve stem belongs to fatigue fracture. [ABSTRACT FROM AUTHOR]

Chinese scholars' performance in international academic community and research on foreign archaeology has brought hot discussion about the internationalization of Chinese archaeology. Based on the databases of the China National Knowledge Infrastructure (CNKI) and the Web of Science core collection (WoS), this paper collected archaeology-related papers published by Chinese scholars in Chinese and world core journals (CCJs and WCJs for short), then filtered translated and original articles about foreign archaeology in CCJs, as well as all original archaeological articles in WCJs. Using Excel, CiteSpace and VOSviewer visualization software, we analyzed these data to give a bird's-eye view of how archaeology research in Mainland China has become internationalized. Chinese archaeology has seen active-interrupt-active phases characterized by learning from foreign academics in the last century. Over the past two decades, the number of articles published in WCJs by scholars from Mainland China has increased significantly, and most research topics are at the forefront of international scholarship. Collaboration networks largely expanded, with the number of Mainland China–led articles increasing significantly. Archaeological papers written by researchers from Mainland China have appeared in a more extensive range of journals, including those with high impact factors. However, articles related to joint Sino-foreign archaeological projects were mostly published in CCJs. The archaeology-related articles published by Chinese scholars in WCJs occupied only a small proportion of all archaeological articles in WCJs. Compared to articles in CCJs, the number of those published by Chinese scholars in WCJs is a drop in the ocean. Therefore the internationalization is not yet a dominant trend and with the introduction of the new inward-looking policy we need more time to observe where the trends of internationalization and localization in Chinese archaeology are heading. [ABSTRACT FROM AUTHOR]

Left atrial ligation (LAL) of the chick embryonic heart is a model of the hypoplastic left heart syndrome (HLHS) where a purely mechanical intervention without genetic or pharmacological manipulation is employed to initiate cardiac malformation. It is thus a key model for understanding the biomechanical origins of HLHS. However, its myocardial mechanics and subsequent gene expressions are not well-understood. We performed finite element (FE) modeling and single-cell RNA sequencing to address this. 4D high-frequency ultrasound imaging of chick embryonic hearts at HH25 (ED 4.5) were obtained for both LAL and control. Motion tracking was performed to quantify strains. Image-based FE modeling was conducted, using the direction of the smallest strain eigenvector as the orientations of contractions, the Guccione active tension model and a Fung-type transversely isotropic passive stiffness model that was determined via micro-pipette aspiration. Single-cell RNA sequencing of left ventricle (LV) heart tissues was performed for normal and LAL embryos at HH30 (ED 6.5) and differentially expressed genes (DEG) were identified.After LAL, LV thickness increased by 33%, strains in the myofiber direction increased by 42%, while stresses in the myofiber direction decreased by 50%. These were likely related to the reduction in ventricular preload and underloading of the LV due to LAL. RNA-seq data revealed potentially related DEG in myocytes, including mechano-sensing genes (Cadherins, NOTCH1, etc.), myosin contractility genes (MLCK, MLCP, etc.), calcium signaling genes (PI3K, PMCA, etc.), and genes related to fibrosis and fibroelastosis (TGF-β, BMP, etc.). We elucidated the changes to the myocardial biomechanics brought by LAL and the corresponding changes to myocyte gene expressions. These data may be useful in identifying the mechanobiological pathways of HLHS. [ABSTRACT FROM AUTHOR]

The helix angle configuration of the myocardium is understood to contribute to the heart function, as finite element (FE) modeling of postnatal hearts showed that altered configurations affected cardiac function and biomechanics. However, similar investigations have not been done on the fetal heart. To address this, we performed image-based FE simulations of fetal left ventricles (LV) over a range of helix angle configurations, assuming a linear variation of helix angles from epicardium to endocardium. Results showed that helix angles have substantial influence on peak myofiber stress, cardiac stroke work, myocardial deformational burden, and spatial variability of myocardial strain. A good match between LV myocardial strains from FE simulations to those measured from 4D fetal echo images could only be obtained if the transmural variation of helix angle was generally between 110 and 130°, suggesting that this was the physiological range. Experimentally discovered helix angle configurations from the literature were found to produce high peak myofiber stress, high cardiac stroke work, and a low myocardial deformational burden, but did not coincide with configurations that would optimize these characteristics. This may suggest that the fetal development of myocyte orientations depends concurrently on several factors rather than a single factor. We further found that the shape, rather than the size of the LV, determined the manner at which helix angles influenced these characteristics, as this influence changed significantly when the LV shape was varied, but not when a heart was scaled from fetal to adult size while retaining the same shape. This may suggest that biomechanical optimality would be affected during diseases that altered the geometric shape of the LV. [ABSTRACT FROM AUTHOR]

Agaricus bisporus production gets a lot of residues, which could be fermented by a continuous stirred tank reactor (CSTR). This research was conducted to study the characteristics of the multiphase flow field in the reactor and its influence on the efficiency of biogas production in the CSTR fermentation process of Agaricus bisporus residue by using CFD numerical simulation technique. The aim is to reveal the relationship between the reactor operating conditions, flow field characteristics, and biogas production efficiency at the micro-level. We compared the results of different turbulence models by evaluating the power quotients and flow quotients with the experimental results to derive the most suitable flow field model inside the reactor for the Agaricus bisporus residues. The results showed that, under the condition that the number of grids does not affect the simulation results, and considering the model accuracy and efficiency, the numerical method can be chosen as the multiple reference frame (MRF) method of the second-order upwind discrete scheme with the realizable k − ε model. In this way, we can make use of edible mushroom residue as a substrate for resource utilization and provide basic data and theoretical basis for the design and scale-up with anaerobic fermentation to biogas reactor. [ABSTRACT FROM AUTHOR]

The strawberry (Fragaria × ananassa) is an economically important perennial crop plant, and its fruits are rich in vitamin C (l-ascorbic acid [AsA]) and other nutrients. l-galactono-1,4-lactone dehydrogenase (GalLDH) is a key enzyme in the terminal step of AsA biosynthesis pathway in plants. Here, the GalLDH gene (FaGalLDH) was cloned from 'Benihoppe' strawberries. AsA content increased during fruit development and peaked at the red-ripening stage, and AsA concentrations in different tissues were correlated with enzyme activity and transcription level of FaGalLDH. Transient over-expression of FaGalLDH in strawberry fruit increased its overall expression and AsA production significantly, whereas transient RNAi of FaGalLDH decreased its expression and AsA content. Furthermore, the optimum pH and temperature for FaGalLDH activity were 8.0 and 25 °C, respectively. Ectopic expression of the FaGalLDH gene in Arabidopsis resulted in higher AsA content and enzyme activity in transgenic lines than in wild-type plants. FaGalLDH over-expression resulted in enhanced tolerance to salt stress due to reduced accumulation of malondialdehyde, H2O2, and O2.−, as well as higher survival rates, root length, proline content, and superoxide dismutase, peroxidase, and catalase activities. These results provide useful information regarding AsA biosynthesis and salt tolerance, which may help to improve strawberry fruit quality and productivity. [ABSTRACT FROM AUTHOR]

Architected materials that actively respond to external stimuli hold tantalizing prospects for applications in energy storage, wearable electronics, and bioengineering. Molybdenum disulfide, an excellent two-dimensional building block, is a promising candidate for lithium-ion battery anode. However, the stacked and brittle two-dimensional layered structure limits its rate capability and electrochemical stability. Here we report the dewetting-induced manufacturing of two-dimensional molybdenum disulfide nanosheets into a three-dimensional foam with a structural hierarchy across seven orders of magnitude. Our molybdenum disulfide foam provides an interpenetrating network for efficient charge transport, rapid ion diffusion, and mechanically resilient and chemically stable support for electrochemical reactions. These features induce a pseudocapacitive energy storage mechanism involving molybdenum redox reactions, confirmed by in-situ X-ray absorption near edge structure. The extraordinary electrochemical performance of molybdenum disulfide foam outperforms most reported molybdenum disulfide-based Lithium-ion battery anodes and state-of-the-art materials. This work opens promising inroads for various applications where special properties arise from hierarchical architecture. The stacked and brittle 2D layered structure of molybdenum disulphide limits its practical application in lithium ion batteries. Here, authors report a dewetting-induced manufacture strategy to create the interpenetrating network and induce the pseudocapacity to improve the electrochemical performance. [ABSTRACT FROM AUTHOR]

Idiopathic tinnitus can cause significant auditory-related brain structural and functional changes in patients. However, changes in patterns of the lateralization effects in idiopathic tinnitus have yet to be established, especially on white matter (WM) reorganization. In this study, we studied 19 left-sided and 19 right-sided idiopathic tinnitus (LSIT, RSIT) patients and 19 healthy controls (HCs). We combined applied voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses to investigate altered features of the auditory-related brain WM. We also conducted correlation analyses between the clinical variables and WM changes in the patients. Compared with the HCs, both sided tinnitus patients showed significant auditory-related brain WM alterations. More interestingly, the LSIT patients demonstrated a greater decrease in white matter volume (WMV) in the right medial superior frontal gyrus (SFG) than the RSIT; meanwhile, we also found that compared with the RSIT group, the LSIT group showed significantly increased fractional anisotropy (FA) in the body of the corpus callosum (CC), left cingulum, and right superior longitudinal fasciculus (SLF) and decreased mean diffusivity (MD) in the body of CC. Moreover, relative to the RSIT group, the LSIT group also exhibited increases in WM axial diffusivity (AD) in the left SLF, left cingulum, right middle cerebellar peduncle (MCP), left thalamus, and bilateral forceps major (FM) and decreases in radial diffusivity (RD) in the genu of CC. Additionally, the FA value of the right SLF was closely associated with tinnitus severity in the LSIT. Our study suggests that lateralization has a significant effect on WM reorganization in patients with idiopathic tinnitus; in particular, LSIT patients may experience more severe and widespread alterations in WMV and WM microstructure than the RSIT group, and all these changes are indirectly auditory related. These findings provide new useful information that can lead to a better understanding of the tinnitus mechanisms. [ABSTRACT FROM AUTHOR]

Fetal critical aortic stenosis with evolving hypoplastic left heart syndrome (CAS-eHLHS) can progress to a univentricular (UV) birth malformation. Catheter-based fetal aortic valvuloplasty (FAV) can resolve stenosis and reduce the likelihood of malformation progression. However, we have limited understanding of the biomechanical impact of FAV and subsequent LV responses. Therefore, we performed image-based finite element (FE) modeling of 4 CAS-eHLHS fetal hearts, by performing iterative simulations to match image-based characteristics and then back-computing physiological parameters. We used pre-FAV simulations to conduct virtual FAV (vFAV) and compared pre-FAV and post-FAV simulations. vFAV simulations generally enabled partial restoration of several physiological features toward healthy levels, including increased stroke volume and myocardial strains, reduced aortic valve (AV) and mitral valve regurgitation (MVr) velocities, reduced LV and LA pressures, and reduced peak myofiber stress. FAV often leads to aortic valve regurgitation (AVr). Our simulations showed that AVr could compromise LV and LA depressurization but it could also significantly increase stroke volume and myocardial deformational stimuli. Post-FAV scans and simulations showed FAV enabled only partial reduction of the AV dissipative coefficient. Furthermore, LV contractility and peripheral vascular resistance could change in response to FAV, preventing decreases in AV velocity and LV pressure, compared with what would be anticipated from stenosis relief. This suggested that case-specific post-FAV modeling is required to fully capture cardiac functionality. Overall, image-based FE modeling could provide mechanistic details of the effects of FAV, but computational prediction of acute outcomes was difficult due to a patient-dependent physiological response to FAV. [ABSTRACT FROM AUTHOR]

Finite Element simulations are a robust way of investigating cardiac biomechanics. To date, it has only been performed with the left ventricle (LV) alone for fetal hearts, even though results are likely different with biventricular (BiV) simulations. In this research, we conduct BiV simulations of the fetal heart based on 4D echocardiography images to show that it can capture the biomechanics of the normal healthy fetal heart, as well as those of fetal aortic stenosis better than the LV alone simulations. We found that performing LV alone simulations resulted in overestimation of LV stresses and pressures, compared to BiV simulations. Interestingly, inserting a compliance between the LV and right ventricle (RV) in the lumped parameter model of the LV only simulation effectively resolved these overestimations, demonstrating that the septum could be considered to play a LV-RV pressure communication role. However, stresses and strains spatial patterns remained altered from BiV simulations after the addition of the compliance. The BiV simulations corroborated previous studies in showing disease effects on the LV, where fetal aortic stenosis (AS) drastically elevated LV pressures and reduced strains and stroke volumes, which were moderated down with the addition of mitral regurgitation (MR). However, BiV simulations enabled an evaluation of the RV as well, where we observed that effects of the AS and MR on pressures and stroke volumes were generally much smaller and less consistent. The BiV simulations also enabled investigations of septal dynamics, which showed a rightward shift with AS, and partial restoration with MR. Interestingly, AS tended to enhance RV stroke volume, but MR moderated that down. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We studied the effects of heterozygous human INS gene mutations on insulin secretion, endoplasmic reticulum (ER) stress and other mechanisms in both MIN6 and human induced pluripotent stem cells (hiPSC)-derived beta-like cells, as well as the effects of prolonged overexpression of mutant human INS in MIN6 cells. Methods: We modelled the structure of mutant C109Y and G32V proinsulin computationally to examine the in silico effects. We then overexpressed either wild-type (WT), mutant (C109Y or G32V), or both WT and mutant human preproinsulin in MIN6 cells, both transiently and stably over several weeks. We measured the levels of human and rodent insulin secreted, and examined the transcript and protein levels of several ER stress and apoptotic markers. We also reprogrammed human donor fibroblasts heterozygous for the C109Y mutation into hiPSCs and differentiated these into pancreatic beta-like cells, which were subjected to single-cell RNA-sequencing and transcript and protein analyses for ER stress and apoptotic markers. Results: The computational modelling studies, and short-term and long-term expression studies in beta cells, revealed the presence of ER stress, organelle changes and insulin processing defects, resulting in a decreased amount of insulin secreted but not the ability to secrete insulin. By 9 weeks of expression of mutant human INS, dominant-negative effects of mutant INS were evident and beta cell insulin secretory capacity declined. INS+/C109Y patient-derived beta-like cells and single-cell RNA-sequencing analyses then revealed compensatory upregulation in genes involved in insulin secretion, processing and inflammatory response. Conclusions/interpretation: The results provide deeper insights into the mechanisms of beta cell failure during INS mutation-mediated diabetes disease progression. Decreasing spliced X-box binding protein 1 (sXBP1) or inflammatory response could be avenues to restore the function of the remaining WT INS allele. [ABSTRACT FROM AUTHOR]

Protracted abstinence (PA) and Methadone maintenance treatment (MMT) are two main types of heroin addiction treatment, however, the effects of both measures on the functional connectivity (FC) of the brain in heroin dependents in the drug cue event-related response are unclear. Functional magnetic resonance imaging (fMRI) based drug cue-reactivity task has been widely used in addiction research, which may provide a new way to understand the change of brain function during a certain period of treatment. The default function network (DMN) with posterior cingulate cortex (PCC) as the core is generally involved in the process of addiction. The aim of the present study was to explore the brain response of FC in patients with heroin-dependent during PA, MMT treatment under task-fMRI. Twenty-two heroin-dependent patients during PA, 18 heroin-dependent patients during MMT and 16 healthy control (HC) individuals were included to conduct the heroin cue-reactivity task during fMRI. The MMT and PA patients' subjective craving for heroin was evaluated. The psychophysiological interaction (PPI) analysis of SPM12 was used to get FC during the task state. There was a significant difference on FC between PCC and the right medial Prefrontal Cortex (mPFC) in three groups. The post-hoc analysis showed that there was a significant difference of brain regions between the MMT and the PA group. The FC of PCC-mPFC in the MMT group was significantly stronger than that in the PA group. Compared with the PA group, the FC of the DMN in the MMT group was significantly increased under drug cue response. Therefore, PA is more beneficial for the heroin-dependent patients to lower the salience value of drug related cues, in turn to reduce relapse risks. It also reflected the important role of PCC-mPFC pathway in heroin dependents induced by heroin cues. [ABSTRACT FROM AUTHOR]

In this work, the spherical TiO2 inverse opal photonic crystals (IOPCs) have been successfully prepared through the combination of sol–gel and liquid phase deposition (LPD) method using SiO2 spheres as the templates. The characterization results show that the spherical TiO2 inverse opal structure can significantly increase the specific surface area and total pore volume. The photocatalytic experiments reveal that the removal rate of Methylene blue (MB) by TiO2 with spherical inverse opal (IO) structure (TiO2-710) was 98% under illumination for 40 min, while the degradation rate of TiO2 without IO structure (TiO2-Sol) was only 17.7%. Moreover, the TiO2-710 sample exhibits the highest reaction rate constant, which is about 9.1 times that of TiO2-Sol. The enhancement of photocatalytic activity can be attributed to the existence of the unique spherical inverse opal structure. [ABSTRACT FROM AUTHOR]

Left atrial ligation (LAL) of the chick embryonic heart at HH21 is a model of the hypoplastic left heart syndrome (HLHS) disease, demonstrating morphological and hemodynamic features similar to human HLHS cases. Since it relies on mechanical intervention without genetic or pharmacological manipulations, it is a good model for understanding the biomechanics origins of such HLHS malformations. To date, however, the fluid mechanical environment of this model is poorly understood. In the current study, we performed 4D ultrasound imaging of LAL and normal chick embryonic hearts and 4D cardiac flow simulations to help shed light on the mechanical environment that may lead to the HLHS morphology. Results showed that the HH25 LAL atrial function was compromised, and velocities in the ventricle were reduced. The HH25 LAL ventricles developed a more triangular shape with a sharper apex, and in some cases, the atrioventricular junction shifted medially. These changes led to more sluggish flow near the ventricular free wall and apex, where more fluid particles moved in an oscillatory manner with the motion of the ventricular wall, while slowly being washed out, resulting in lower wall shear stresses and higher oscillatory indices. Consequent to these flow conditions, at HH28, even before septation is complete, the left ventricle was found to be hypoplastic while the right ventricle was found to be larger in compensation. Our results suggest that the low and oscillatory flow near the left side of the heart may play a role in causing the HLHS morphology in the LAL model. [ABSTRACT FROM AUTHOR]

Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health. [ABSTRACT FROM AUTHOR]

Critical aortic stenosis (AS) of the fetal heart causes a drastic change in the cardiac biomechanical environment. Consequently, a substantial proportion of such cases will lead to a single-ventricular birth outcome. However, the biomechanics of the disease is not well understood. To address this, we performed Finite Element (FE) modelling of the healthy fetal left ventricle (LV) based on patient-specific 4D ultrasound imaging, and simulated various disease features observed in clinical fetal AS to understand their biomechanical impact. These features included aortic stenosis, mitral regurgitation (MR) and LV hypertrophy, reduced contractility, and increased myocardial stiffness. AS was found to elevate LV pressures and myocardial stresses, and depending on severity, can drastically decrease stroke volume and myocardial strains. These effects are moderated by MR. AS alone did not lead to MR velocities above 3 m/s unless LV hypertrophy was included, suggesting that hypertrophy may be involved in clinical cases with high MR velocities. LV hypertrophy substantially elevated LV pressure, valve flow velocities and stroke volume, while reducing LV contractility resulted in diminished LV pressure, stroke volume and wall strains. Typical extent of hypertrophy during fetal AS in the clinic, however, led to excessive LV pressure and valve velocity in the FE model, suggesting that reduced contractility is typically associated with hypertrophy. Increased LV passive stiffness, which might represent fibroelastosis, was found to have minimal impact on LV pressures, stroke volume, and wall strain. This suggested that fibroelastosis could be a by-product of the disease progression and does not significantly impede cardiac function. Our study demonstrates that FE modelling is a valuable tool for elucidating the biomechanics of congenital heart disease and can calculate parameters which are difficult to measure, such as intraventricular pressure and myocardial stresses. [ABSTRACT FROM AUTHOR]

Citrus fruit granulation is a major physical disorder during late maturity and post-harvest storage, and it greatly undermines the quality of fruit. Currently, there is still a lack of rapid and nondestructive methods to detect citrus granulation. This study proposes a nondestructive granulation detecting method based on deep learning. Different models were established with the input of preprocessed transmission spectra obtained by hyperspectral imaging. Conventional convolution neural network (CNN) got the best accuracy at 88.02% for training, compared with the least-square support vector machine (LS-SVM) and back-propagation neural network (BP-NN). After adding the batch-normalization layer to the CNN, the experimental results show that the detection model obtained a 100% accuracy in train set and 97.9% in validation set, respectively. And then, through analyzing the well-trained model layer by layer, bands of 660.2–721.1 nm, 708.5–750 nm and 806.5–847 nm were the spectra greatly related to granulation. The model rebuilt with these feature bands obtained 90.1% and 85.4% accuracy in train set and validation set, respectively. This way, effective wavelength selection can find bands highly correlated with granulation.Combined with some research on functional group, it is possible that inference to internal matter changes in granulation process, which may provide some hints to explore the reason of granulation. It is also meaningful to develop granulation-detecting equipment for citrus fruits. [ABSTRACT FROM AUTHOR]

Methadone maintenance treatment (MMT) and protracted abstinence (PA) are common methods of therapy in heroin addiction as both suppress the craving for drug use. However, the difference in patterns of brain function between two groups is unknown. Functional magnetic resonance imaging (fMRI) based drug cue-reactivity task is a good tool to understand the change of brain function during a certain period of treatment. Twenty-three heroin-dependent patients during PA, 18 heroin-dependent patients during MMT and 20 healthy control (HC) individuals were included to conduct the heroin cue-reactivity task during fMRI. The MMT and PA patients' subjective craving for heroin was evaluated. Differences among the three groups were analyzed with respect to heroin cue induced brain responses. Compared with HC group, MMT and PA groups commonly demonstrated significantly higher brain responses during exposure of heroin-related cues in the bilateral caudate, right thalamus, left hippocampus, parahippocampus, midbrain, left superior parietal lobule, right middle occipital gyrus, left posterior cingulate cortex and right cerebellum. However, compared with PA group, MMT group demonstrated significantly greater brain response mainly in right caudate, hippocampus, midbrain left fusiform, right inferior parietal lobule, left posterior cingulate cortex, cerebellum and postcentral gyrus. No difference in cue induced craving between MMT and PA groups was found. The findings suggest that MMT group demonstrated more enhanced drug cue induced brain responses than PA group, indicating that, these two treatments have different effect on patterns of brain response to heroin related cues in heroin-dependent individuals. [ABSTRACT FROM AUTHOR]

The treatment of atypical femoral shaft fractures with abnormal bowing provides a unique challenge for surgeons. Whilst intramedullary fixation of atypical femoral shaft fractures affords both mechanical and biological benefits, the mismatch between standard intramedullary devices and the abnormal femoral bowing in these patients makes this method of fixation challenging for the surgeon. The purpose of this manuscript is to illustrate the evolution of our surgical technique through a series of four patients. The critical factors we identified include lateral positioning of the patient for reduction, the use of a piriformis-start nail, and an entry point that was anterior in the sagittal profile and lateral in the coronal profile. This technique was easily replicable, facilitated more anatomical reduction and aided in avoiding complications. [ABSTRACT FROM AUTHOR]

The embryonic outflow tract (OFT) eventually undergoes aorticopulmonary septation to form the aorta and pulmonary artery, and it is hypothesized that blood flow mechanical forces guide this process. We performed detailed studies of the geometry, wall motions, and fluid dynamics of the HH25 chick embryonic OFT just before septation, using noninvasive 4D high-frequency ultrasound and computational flow simulations. The OFT exhibited expansion and contraction waves propagating from proximal to distal end, with periods of luminal collapse at locations of the two endocardial cushions. This, combined with periods of reversed flow, resulted in the OFT cushions experiencing wall shear stresses (WSS or flow drag forces) with elevated oscillatory characteristics, which could be important to signal for further development of cushions into valves and septum. Furthermore, the OFT exhibits interesting double-helical flow during systole, where a pair of helical flow structures twisted about each other from the proximal to distal end. This coincided with the location of the future aorticopulmonary septum, which also twisted from the proximal to distal end, suggesting that this flow pattern may be guiding OFT septation. [ABSTRACT FROM AUTHOR]

The lipid droplet (LD)-associated protein adipose differentiation-related protein (ADRP or PLIN2) is required for the formation and stability of the LD organelle, whereas its biological roles are still obscure. Herein, we show that PLIN2 is the most abundant protein on the lipid droplets (LDs) of mouse myoblast cell line C2C12. Both the expression of PLIN2 and the accumulation of LDs were up-regulated in a time- and dose-dependent manner when the cells were treated with oleate (OA). The protein level of PLIN2 was positively correlated with the formation of LDs, suggesting that LDs stabilize PLIN2. Furthermore, knocking out PLIN2 in C2C12 cells led to enlarged LDs and higher triacylglycerol hydrolysis activity. The isolated PLIN2 null LDs became closely contact with mitochondria and other cellular organelles. Additionally, mitochondrial activity was suppressed by OA in PLIN2 null cells. Our results reveal the pivotal roles of PLIN2 in governing LD dynamics and their relationship to mitochondria, and suggest a reciprocal stabilization between PLIN2 and LDs. [ABSTRACT FROM AUTHOR]

During the on-orbit operation of BeiDou satellites, the on board atomic clocks of these satellites are easily affected by changes in the space environment. Since the clock offsets of BeiDou satellites derived from multi-satellite clock estimation exhibit correlation among one another. In this study, the correlation among the clock offsets of BeiDou satellites is analyzed and the influence of correlation among satellites on clock offset prediction accuracy is investigated. To obtain accurate analysis results, the Baarda outlier detection method is initially improved. The improved method can effectively eliminate small errors in clock offset data. Then, the correlation coefficient among BeiDou satellites is calculated, and the method based on the correlation among BeiDou satellite clocks is used to predict the clock offsets of the satellites. Experimental results show that clock offset prediction accuracy can be improved by 7.3% compared with that of the traditional method when the method that considers correlation among satellite clocks is used. [ABSTRACT FROM AUTHOR]

For better understanding of bone-conducted (BC) hearing, a mechanical BC model is formulated using the Wentzel-Kramers-Brillouin (WKB) method. The BC hearing can be generally described by three main mechanisms: (1) cochlear fluid inertia, (2) in-phase motion of the outer bony shell, and (3) out-of-phase motion of the outer bony shell. Specifically, the second and third mechanisms can be identically explained by symmetric pressure compression-expansion and anti-symmetric compression-expansion, respectively. In this study, simulation results show that both the symmetric and anti-symmetric compression-expansion modes become significant at frequencies above 7 kHz while the fluid inertial mode is dominant at lower frequencies. The density difference between the scala fluid and soft cells of basilar membrane and the amplitude of the anti-symmetric compression-expansion input are identified as the difference between the air conduction and bone conduction. The natural frequency of the cochlear duct wall determines the magnitudes between the three mechanism and is approximated to be in the order of 10 MHz and above. [ABSTRACT FROM AUTHOR]

Objective: To determine whether emodin facilitates the mesenchymal–epithelial transition (MET) of endometrial stromal cells (ESCs) as well as to explore the mechanism through which emodin favored the MET of ESCs. Methods: Cell viability was tested by methyl thiazolyl tetrazolium assay. Cell migration and invasion abilities were detected by transwell assays. Levels of integrin-linked kinase (ILK) and epithelial–mesenchymal transition (EMT)-related proteins were detected by Western blot. Results: Upregulated ILK and increased abilities of migration and invasion were confirmed in the eutopic and ectopic ESCs (EuSCs and EcSCs), especially in the EcSCs. After treated with emodin, the expression of ILK was statistically downregulated in EcSCs, resulting in the MET and decreased migration and invasion abilities of EcSCs. Additionally, silencing of the ILK gene in EcSCs also achieved the above-mentioned effects, which were strengthened by emodin. Furthermore, exogenous expression of ILK in control ESCs (CSCs) resulted in the EMT and increased abilities of migration and invasion of CSCs, which can be abrogated by emodin. Besides, exogenous expression of ILK also abrogated the effects of emodin on CSCs. Conclusion: Emodin inhibits the migration and invasion abilities of human ESCs by facilitating the MET through targeting ILK. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether postoperative GnRH agonist (GnRH-a) treatment can prevent endometriosis recurrence.Methods: This meta-analysis searched PubMed, Embase and Cochrane Library for relevant studies published online before June 2015. Seven randomized controlled trials including 328 patients with postoperative GnRH-a treatment and 394 patients in control group were included in the meta-analysis. In the meta-analysis, the recurrence rate of GnRH-a group compared with control group was evaluated with odds ratio (OR) and its 95 % confidence interval (CI). Heterogeneity, small study effect and publication bias were, respectively, assessed using Higgins I (2), sensitivity analysis and funnel plot.Results: Postoperative GnRH-a treatment for endometriosis (pooled OR = 0.71; 95 % CI 0.52-0.96) was superior to expectant or placebo treatment in prevention of the recurrence. The recurrence rate decreased significantly in patients who received 6 months GnRH-a treatment (pooled OR = 0.59, 95 % CI 0.38-0.90), whereas no significant difference of recurrence rate existed between patients with 3 months post-surgical GnRH-a therapy and the control group (pooled OR = 0.87, 95 % CI 0.56-1.34). No significant heterogeneity and small study effect were found in the meta-analysis. However, publication bias did existed in the present meta-analysis.Conclusions: Longer-term (6 months) postoperative administration of GnRH-a can decrease the recurrence risk of endometriosis, whereas 3 months duration of GnRH-a therapy makes no significant difference in preventing the recurrence of endometriosis. Therefore, instead of a 3 month therapy, the duration of the postoperative administration should be longer enough (6 months) to prevent the recurrence of endometriosis. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a common autoimmune disease associated with progressive disability, systemic complications, and early death. Multiple lines of evidence have placed adaptive immune responses in the center of RA pathogenesis. However, the functional roles of T helper cells are insufficiently described. Here, we examined the Th2 cell subsets and their functions in RA patients. A downregulation of IL-4 cells in CD4 T cells were observed in RA patients, indicating a downregulation of Th2 cells, and these results were confirmed by using and CXCR3 and CCR6 surface markers. We then found that CXCR3CCR6 Th2 cells can be separated into IL-4 (single positive), IL-10 (single positive), and IL-4IL-10 (double positive) subsets. Further results showed that CXCR5 only expressed on IL-10+ Th2 cells. The CXCR5 and CXCR5 Th2 cells each exhibited distinctive features in helping B cell antibody secretion. CXCR5 Th2 cells were more potent at stimulating total Ig and IgM secretion, while CXCR5 Th2 cells were more potent at stimulating IgE. IL-10 was required for helping B cell total Ig, IgM, and IgE production, while IL-4 was required for total Ig and IgE. The frequencies of IL-10 and IL-4IL-10 Th2 cells were positively correlated with rheumatoid factor titer in vivo. Together, our study demonstrated distinctive subsets within Th2 cells, each with different impacts on antibody production and RA disease. [ABSTRACT FROM AUTHOR]

We consider group scheduling problem on a single machine with multiple due windows assignment. Jobs are divided into groups in advance according to their processing similarities, and all jobs of the same group are required to be processed contiguously on the machine in order to achieve production efficiency and save time/money resource. A sequence-independent setup time precedes the processing of each group. The goal is to determine the optimal sequence for both groups and jobs, together with an optimal combination of the due windows assignment strategy so as to minimize the total of earliness, tardiness and due windows related costs. We give an $$O(n\log n)$$ time algorithm for the problem. [ABSTRACT FROM AUTHOR]

This paper studies single machine scheduling with a fixed non-availability interval. The processing time of a job is a linear increasing function of its starting time, and each job has a release date. A job is either rejected by paying a penalty cost or accepted and processed on the machine. The objective is to minimize the makespan of the accepted jobs and the total rejection penalties of the rejected jobs. We present a fully polynomial-time approximation scheme for the problem. We also show that the special case without non-availability interval can be solved using the same method with a lower order. [ABSTRACT FROM AUTHOR]

Nondestructive detection of fruit ripeness is crucial for improving fruits' shelf life and industry production. This work illustrates the use of hyperspectral images at the wavelengths between 400 and 1,000 nm to classify the ripeness of persimmon fruit. Spectra and images of 192 samples were investigated, which were selected from four ripeness stages (unripe, mid-ripe, ripe, and over-ripe). Three classification models-linear discriminant analysis (LDA), soft independence modeling of class analogy, and least squares support vector machines were compared. The best model was LDA, of which the correct classification rate was 95.3 % with the input consisted of the spectra and texture feature of images at three feature wavelengths (518, 711, and 980 nm). Feature wavelengths selection and texture feature extraction were based on successive projection algorithm and gray level co-occurrence matrix, respectively. In addition, using the same input of ripeness detection to make an investigation on firmness prediction by partial least square analysis showed a potential for further study, with correlate coefficient of prediction set r of 0.913 and root mean square error of prediction of 4.349. The results in this work indicated that there is potential in the use of hyperspectral imaging technique on non-destructive ripeness classification of persimmon. The experimental results could provide the theory support for studying online quality control of persimmon. [ABSTRACT FROM AUTHOR]

This research investigated the feasibility of Fourier transform near-infrared (FT-NIR) spectral technique in determining branched-amino acid contents (Leucine, Isolecucine, and Valine) in fermented Cordyceps sinensis ( C. sinensis) mycelium. A comparison of two variable selection methods, namely competitive adaptive reweighted sampling (CARS) and genetic algorithms, showed that CARS achieved better performance calibrating by partial least square regression or least squares support vector machine methods, with the effective wavelengths mainly concentrated around 12,010-10,050, 7,500-6,000, and 5,000-4,000 cm. For the quantitative determination of Val, Ile, and Leu by the established models, root mean square error of prediction were 0.0662, 0.0594, and 0.0678; correlation coefficients were 0.80, 0.83, and 0.90; residual predictive deviation were 1.66, 1.78, and 2.30, respectively. This study showed that the FT-NIR spectral technique has a potential to determine branched chain amino acids in fermented C. sinensis mycelium and further to facilitate quality control during its production. [ABSTRACT FROM AUTHOR]

The dorsal anterior cingulate cortex (dACC) has been consistently implicated in cognitive control processes. Many studies have found higher fractional anisotropy (FA) in the left anterior cingulum bundle (aCB) than in the right. However, the asymmetry of gray matter density (GMD) is not clear. Using multiple modalities of MRI, we investigated both FA and GMD in the dACC in two independent groups of healthy participants (50 per group, 18-24 years old, half males and half females). Consistent with previous findings, the mean FA of the left aCB was significantly higher than that of the right. Males showed higher FA in the bilateral aCB than females. Voxel-based analysis of GMD in the dACC presented a region-specific significant asymmetry: right > left in the lower part (around callosal sulcus) but left > right in the upper part (around cingulate sulcus). No significant sex effect was found for GMD in the dACC. All these results were almost the same across the two independent groups. The complex pattern of asymmetry in GMD may imply highly differentiated functions of the dACC. Future fine-scale structural and diffusion MRI studies and a battery of cognitive behavioral measurements are needed to fully elucidate the asymmetry of the dACC. [ABSTRACT FROM AUTHOR]

Abstract  Recent studies suggest that carbon monoxide (CO), which is mainly produced by heme oxygenase (HO EC 1.14.99.3), may function as a physiological messenger or bioactive molecule by interacting with nitric oxide (NO) in animal cells. In this study, we report that application of the hematin and hemin, two heme molecules cleaved by HO to yield CO in animals, dose-dependently induced the significant increase in wheat root elongation as well as the actions of IAA and NO donor sodium nitroprusside (SNP). These responses were mimicked by the application of aqueous solution of CO with different saturation. Also, above heme molecule-induced effect is specific for CO since the potent inhibitor of HO-1, zinc protoporphyrin-IX (ZnPPIX) or CO scavenger hemoglobin (Hb) blocked the action of hematin and hemin, respectively. Further results proved that treatment with hematin or IAA could result in either the potent induction of HO-1 transcript or CO releasing in wheat root segments, both of which were reversed by the addition of ZnPPIX. ZnPPIX with lower concentration could prevent the elongation induced by IAA, while in the SNP-treatment the prevention of root growth occurred solely at higher concentrations. Also, wheat root segments elongation induced by IAA, SNP or hematin, was blocked by the specific NO scavenger, inhibitors of NO synthase (NOS) and guanylate cyclase (GC), respectively. Meanwhile, production of reactive oxygen species (ROS) could be demonstrated in the growing zone of wheat root segments treated by hematin or SNP using specific histochemical assay combined with the inhibitor investigation. Taken together, above results suggested that CO produced by HO might mediate the induction of growth elongation of wheat root segments by IAA, which might be also related to NO/cGMP- and even ROS-dependent pathways. [ABSTRACT FROM AUTHOR]

Introduction: Metastasis is responsible for 90% of cancer-related deaths worldwide. However, the potential inhibitory effects of metastasis by various anticancer drugs have been left largely unexplored. Existing preclinical models primarily focus on antiproliferative agents on the primary tumor to halt the cancer growth but not in metastasis. Unlike primary tumors, metastasis requires cancer cells to exert sufficient cellular traction force through the actomyosin machinery to migrate away from the primary tumor site. Therefore, we seek to explore the potential of cellular traction force as a novel readout for screening drugs that target cancer metastasis.In vitro models of invasive and non-invasive breast cancer were first established using MDA-MB-231 and MCF-7 cell lines, respectively. Cellular morphology was characterized, revealing spindle-like morphology in MDA-MB-231 and spherical morphology in MCF-7 cells. The baseline cellular traction force was quantified using the Traction force Microscopy technique. Cisplatin, a paradigm antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, were selected to evaluate the potential of cellular traction force as a drug testing readout for the in vitro cancer metastasis.MDA-MB-231 cells exhibited significantly higher baseline cellular traction force compared to MCF-7 cells. Treatment with Cisplatin, an antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, demonstrated distinct effects on cellular traction force in MDA-MB-231 but not in MCF-7 cells. These findings correlate with the invasive potential observed in the two models.Cellular traction force emerges as a promising metric for evaluating drug efficacy in inhibiting cancer metastasis using in vitro models. This approach could enhance the screening and development of novel anti-metastatic therapies, addressing a critical gap in current anticancer drug research.Methods: Metastasis is responsible for 90% of cancer-related deaths worldwide. However, the potential inhibitory effects of metastasis by various anticancer drugs have been left largely unexplored. Existing preclinical models primarily focus on antiproliferative agents on the primary tumor to halt the cancer growth but not in metastasis. Unlike primary tumors, metastasis requires cancer cells to exert sufficient cellular traction force through the actomyosin machinery to migrate away from the primary tumor site. Therefore, we seek to explore the potential of cellular traction force as a novel readout for screening drugs that target cancer metastasis.In vitro models of invasive and non-invasive breast cancer were first established using MDA-MB-231 and MCF-7 cell lines, respectively. Cellular morphology was characterized, revealing spindle-like morphology in MDA-MB-231 and spherical morphology in MCF-7 cells. The baseline cellular traction force was quantified using the Traction force Microscopy technique. Cisplatin, a paradigm antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, were selected to evaluate the potential of cellular traction force as a drug testing readout for the in vitro cancer metastasis.MDA-MB-231 cells exhibited significantly higher baseline cellular traction force compared to MCF-7 cells. Treatment with Cisplatin, an antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, demonstrated distinct effects on cellular traction force in MDA-MB-231 but not in MCF-7 cells. These findings correlate with the invasive potential observed in the two models.Cellular traction force emerges as a promising metric for evaluating drug efficacy in inhibiting cancer metastasis using in vitro models. This approach could enhance the screening and development of novel anti-metastatic therapies, addressing a critical gap in current anticancer drug research.Results: Metastasis is responsible for 90% of cancer-related deaths worldwide. However, the potential inhibitory effects of metastasis by various anticancer drugs have been left largely unexplored. Existing preclinical models primarily focus on antiproliferative agents on the primary tumor to halt the cancer growth but not in metastasis. Unlike primary tumors, metastasis requires cancer cells to exert sufficient cellular traction force through the actomyosin machinery to migrate away from the primary tumor site. Therefore, we seek to explore the potential of cellular traction force as a novel readout for screening drugs that target cancer metastasis.In vitro models of invasive and non-invasive breast cancer were first established using MDA-MB-231 and MCF-7 cell lines, respectively. Cellular morphology was characterized, revealing spindle-like morphology in MDA-MB-231 and spherical morphology in MCF-7 cells. The baseline cellular traction force was quantified using the Traction force Microscopy technique. Cisplatin, a paradigm antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, were selected to evaluate the potential of cellular traction force as a drug testing readout for the in vitro cancer metastasis.MDA-MB-231 cells exhibited significantly higher baseline cellular traction force compared to MCF-7 cells. Treatment with Cisplatin, an antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, demonstrated distinct effects on cellular traction force in MDA-MB-231 but not in MCF-7 cells. These findings correlate with the invasive potential observed in the two models.Cellular traction force emerges as a promising metric for evaluating drug efficacy in inhibiting cancer metastasis using in vitro models. This approach could enhance the screening and development of novel anti-metastatic therapies, addressing a critical gap in current anticancer drug research.Conclusion: Metastasis is responsible for 90% of cancer-related deaths worldwide. However, the potential inhibitory effects of metastasis by various anticancer drugs have been left largely unexplored. Existing preclinical models primarily focus on antiproliferative agents on the primary tumor to halt the cancer growth but not in metastasis. Unlike primary tumors, metastasis requires cancer cells to exert sufficient cellular traction force through the actomyosin machinery to migrate away from the primary tumor site. Therefore, we seek to explore the potential of cellular traction force as a novel readout for screening drugs that target cancer metastasis.In vitro models of invasive and non-invasive breast cancer were first established using MDA-MB-231 and MCF-7 cell lines, respectively. Cellular morphology was characterized, revealing spindle-like morphology in MDA-MB-231 and spherical morphology in MCF-7 cells. The baseline cellular traction force was quantified using the Traction force Microscopy technique. Cisplatin, a paradigm antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, were selected to evaluate the potential of cellular traction force as a drug testing readout for the in vitro cancer metastasis.MDA-MB-231 cells exhibited significantly higher baseline cellular traction force compared to MCF-7 cells. Treatment with Cisplatin, an antimetastatic drug, and 5-Fluorouracil (5FU), a non-antimetastatic drug, demonstrated distinct effects on cellular traction force in MDA-MB-231 but not in MCF-7 cells. These findings correlate with the invasive potential observed in the two models.Cellular traction force emerges as a promising metric for evaluating drug efficacy in inhibiting cancer metastasis using in vitro models. This approach could enhance the screening and development of novel anti-metastatic therapies, addressing a critical gap in current anticancer drug research. [ABSTRACT FROM AUTHOR]