Search

Laser directed energy deposition (DED-LB) technology is currently facing challenges in controlling geometry accuracy of metal components. There is an urgent need to develop a numerical model that is more efficient and accurate compared to existing models and to analyze the dynamic behavior of the melt pool under the interaction of process parameters during DED-LB process to optimize parameters with fewer experimental studies to reduce costs. Therefore, a three-dimensional powder-scale multi-physics model is proposed during the single-track DED-LB process in this study. The powder particles are added by a Lagrangian particle model in this model without the need for assuming that the powder particles entering the molten pool are added by the mass source term, which improves model accuracy and efficiency. The effects of energy per unit mass (EUM, J g−1), mass per unit length (MUL, g mm−1), and standoff distance (SD, mm) intensities on transient molten pool motion and flow field are comprehensively investigated. It is discovered that the proposed model is able to predict the single-track height, width, depth, and dilution rate, or less than 9% relative error from experimentation, providing a useful tool for track geometry to predict. Furthermore, the flow velocity, width, and depth of melt pool also gradually are improved with higher EUM, MUL, and SD intensity and fluctuate within a small range. However, the height is improved and then decreases with higher SD intensity, and is improved with higher EUM or MUL. Overall, this study contributes to developing an optimizing process approach to improve formation accuracy for DED-LB manufacturing. [ABSTRACT FROM AUTHOR]

At present, in the directed energy deposition (DED) of metals, the heat transfer of the melt pool and microstructural evolution are not fully understood. This study investigates the thermal effect on the microstructure and the mechanical properties of DED AISI 316L, using in situ optical monitoring. Five thin-wall samples were tested to determine the effect on microstructural evolution and mechanical properties with variable laser powers and scanning speeds. A comprehensive optical monitoring system with a CMOS (coaxial complementary metal oxide semiconductor) visual module and an infrared camera was adopted in analyzing the temperature gradient and the solidification rate. The emissivity of the melt pool was calibrated, using the melt pool length, extracted from the coaxial visual image. The results showed that microstructures mainly consist of the coarse columnar grain and the equiaxed grain at the top layer of AISI 316L samples. The direction of epitaxial growth of columnar grains is affected by the compromise between directional heat flux and crystallographic direction. High numerical temperature gradient and high solidification rate are beneficial to obtaining fine grain size and high yield stress. A modified microstructure map for DED AISI316L was established, which correlates the solidification parameters with a solidification microstructure. This research study, combining temperature distribution, solidification parameter, microstructure, and tensile property, provides an experimental identification of solidification parameters and the model on the solidification theory for precision control of DED process. [ABSTRACT FROM AUTHOR]

Background: To evaluate whether increasing total gonadotropin (Gn) dose is associated with changes in euploid blastocyst rate in preimplantation genetic testing (PGT) oocytes. Methods: This retrospective cohort study was conducted between 2017 and 2022, and 19,246 oocytes were grouped and analyzed based on tri-sectional quantiles of total Gn doses. Setting: Single reproductive medical center. Subjects: All the patients who underwent PGT cycles, including PGT for aneuploidy, monogenic disorders, and structural rearrangements, were included. Exposure: Next-generation sequencing platforms for chromosomal analysis. Main outcome measures.: Blastocyst formation and euploid blastocyst rates. Results: In total, 19,246 oocytes and 5375 PGT blastocysts were analyzed. There were significant differences in blastocyst formation and euploid blastocyst rates among the groups classified according to tri-sectional quantiles of total Gn doses. Significant differences in age, body mass index (BMI), proportion of primary infertility, anti-Müllerian hormone (AMH) levels, number of oocytes retrieved, controlled ovarian stimulation (COS) regimen, type of Gn, and PGT category were observed among the three groups. After stratifying the analysis by age, BMI, infertility diagnosis, AMH levels, number of oocytes retrieved, PGT category, type of Gn, and COS regimen, significant differences were only seen in a small number of specific subgroups. Furthermore, the results of the multiple logistic regression analysis showed that the blastocyst formation and euploid blastocyst rates did not significantly increase or decrease with the total Gn dose, whether treated as a continuous variable or divided into three Gn groups as categorical variables. Notably, advancing age was a risk factor for blastocyst formation and euploid blastocyst rates. PGT for structural rearrangements was a risk factor for blastocyst formation and euploid blastocyst rates as compared with PGT for aneuploidy. Conclusion: In the total PGT cycles, advancing age, and preimplantation genetic testing for structural rearrangements negatively affected blastocyst formation and euploid blastocyst rates; however, the total Gn dose did not affect blastocyst formation and euploid blastocyst rates. [ABSTRACT FROM AUTHOR]

To extend the limited evidence on how hot spot policing (HSP) strategies affect community experiences, perceptions, and attitudes, police agencies in two cities participated in a randomized experiment involving 102 hot spots that were assigned to a control condition (n = 51) or to receive a HSP program emphasizing patrol, community engagement, and problem-solving for 14–17 months during 2019 and 2020 (n = 51). Cross-sectional surveys with hot spot community members were conducted in person before the program (n = 1082) and, due to COVID-19, by mail and internet afterwards (n = 768) to assess program effects on crime victimization, views of crime and disorder, and attitudes towards police. In both cities, the evaluation period overlapped with the COVID-19 pandemic and the national protests for police reform following the killing of George Floyd by police in Minneapolis during 2020; in one city, the program was ongoing during these events. Results showed the program had few effects on community experiences and views, though there were some indications it may have improved perceptions of police legitimacy and police misconduct in one city. The findings suggest that HSP strategies do not have harmful effects on community perceptions and might improve some aspects of police-community relations. However, weak program implementation, challenges to survey administration, and the occurrence of both COVID-19 and the George Floyd incident during the study period complicate interpretation of the results. [ABSTRACT FROM AUTHOR]

Aims/Introduction: We investigated the relationship of circulating TSP‐1 mRNA and miR‐194 with diabetic kidney disease's degree. Materials and Methods: We enrolled 167 hospitalized type 2 diabetes patients in the endocrinology department. Patients were split into three groups according to urinary microalbumin: A, B and C. The control group comprised healthy outpatients (n = 163). The quantities of microribonucleic acid (miR)‐194 and thrombospondin‐1 (TSP‐1) messenger ribonucleic acid (mRNA) in the participants' circulation were measured using a quantitative real‐time polymerase chain reaction. Results: Circulating TSP‐1 mRNA (P = 0.024) and miR‐194 (P = 0.029) expressions significantly increased in type 2 diabetes patients. Circulating TSP‐1 mRNA (P = 0.040) and miR‐194 (P = 0.007) expression levels differed significantly among the three groups; circulating TSP‐1 mRNA expression increased with urinary microalbumin. However, miR‐194 declined in group B and increased in group C. Circulating TSP‐1 mRNA was positively correlated with cystatin‐c (r = 0.281; P = 0.021) and microalbumin/creatinine ratio (UmALB/Cr; r = 0.317; P = 0.009); miR‐194 was positively correlated with UmALB/Cr (r = 0.405; P = 0.003). Stepwise multivariate linear regression analysis showed cystatin‐c (β = 0.578; P = 0.021) and UmALB/Cr (β = 0.001; P = 0.009) as independent factors for TSP‐1 mRNA; UmALB/Cr (β = 0.005; P = 0.028) as an independent factor for miR194. Areas under the curve for circulating TSP‐1 mRNA and miR194 were 0.756 (95% confidence interval 0.620–0.893; sensitivity 0.69 and specificity 0.71, P < 0.01) and 0.584 (95% confidence interval 0.421–0.748; sensitivity 0.54 and specificity 0.52, P < 0.01), respectively. Conclusions: Circulating TSP‐1 mRNA and miR‐194 expressions significantly increased in type 2 diabetes patients. The microalbumin group had lower levels of miR‐194 (a risk factor that is valuable for type 2 diabetes kidney disease evaluation). [ABSTRACT FROM AUTHOR]

Leaf area index (LAI) is a vital input variable for crop growth and yield prediction models. Therefore, rapid and accurate crop LAI estimates can offer important information for monitoring and managing the quantity and quality of food production. Here, LAI values of maize and soybean were predicted applying height metrics and intensity metrics calculated through unmanned aerial vehicle (UAV) LiDAR data. Moreover, we compared the prediction performance of physical model with that of empirical model for estimating crop LAI. The physical model based on Beer–Lambert law yielded reliable estimation results using LiDAR height data (maize: R2 = 0.815, RMSE = 0.385; soybean: R2 = 0.627, RMSE = 0.515) and LiDAR intensity data (maize: R2 = 0.719, RMSE = 0.474; soybean: R2 = 0.548, RMSE = 0.567). However, the linear regression model obtained a higher estimation accuracy. The single linear regression model derived from LiDAR height data had an R2 value of 0.837 (RMSE = 0.361) for maize and 0.658 (RMSE = 0.493) for soybean, and derived from LiDAR intensity data had an R2 value of 0.749 (RMSE = 0.448) for maize and 0.460 (RMSE = 0.619) for soybean, respectively. We found that the random forest (RF) regression model yielded the lowest estimation accuracy in this study. Moreover, the RF regression model in our study was not able to reliably estimate soybean LAI whether using LiDAR height metrics (R2 = 0.294) or intensity metrics (R2 = 0.180). Our results show that both LiDAR intensity and height metrics are capable of reliably predicting maize and soybean LAIs, although LiDAR intensity data yielded lower estimation accuracy than LiDAR height data. In conclusion, the results presented in this study demonstrate that using UAV-LiDAR technology to predict crop LAI is a flexible, practical, and cost-effective method. [ABSTRACT FROM AUTHOR]

As an advanced metal additive manufacturing technology, laser-directed energy deposition (DED-LB) has attracted a lot of attention in recent years, and is increasingly used in aerospace, automotive, marine, and biomedical applications. However, as industry application standards continue to improve, the challenges of part quality, process stability, and molding efficiency faced by DED-LB are becoming more and more prominent. On-line monitoring and real-time quality regulation can effectively avoid quality defects in processing, which is an effective measure to solve the problem. This paper summarizes the current research status of on-line monitoring means and closed-loop quality regulation technology for DED-LB. The on-line monitoring signals and related sensing devices mainly based on image signals, temperature signals, spectral signals, acoustic emission signals, and X-ray imaging, as well as the closed-loop control strategies and intelligent optimization methods in the process are discussed. Finally, a view on the future direction of on-line monitoring-control system for DED-LB is presented. [ABSTRACT FROM AUTHOR]

Background: The aberrant expression of phosphofructokinase-platelet (PFKP) plays a crucial role in the development of various human cancers by modifying diverse biological functions. However, the precise molecular mechanisms underlying the role of PFKP in head and neck squamous cell carcinoma (HNSCC) are not fully elucidated. Methods: We assessed the expression levels of PFKP and c-Myc in tumor and adjacent normal tissues from 120 HNSCC patients. A series of in vitro and in vivo experiments were performed to explore the impact of the feedback loop between PFKP and c-Myc on HNSCC progression. Additionally, we explored the therapeutic effects of targeting PFKP and c-Myc in HNSCC using Patient-Derived Organoids (PDO), Cell Line-Derived Xenografts, and Patients-Derived Xenografts. Results: Our findings indicated that PFKP is frequently upregulated in HNSCC tissues and cell lines, correlating with poor prognosis. Our in vitro and in vivo experiments demonstrate that elevated PFKP facilitates cell proliferation, angiogenesis, and metastasis in HNSCC. Mechanistically, PFKP increases the ERK-mediated stability of c-Myc, thereby driving progression of HNSCC. Moreover, c-Myc stimulates PFKP expression at the transcriptional level, thus forming a positive feedback loop between PFKP and c-Myc. Additionally, our multiple models demonstrate that co-targeting PFKP and c-Myc triggers synergistic anti-tumor effects in HNSCC. Conclusion: Our study demonstrates the critical role of the PFKP/c-Myc positive feedback loop in driving HNSCC progression and suggests that simultaneously targeting PFKP and c-Myc may be a novel and effective therapeutic strategy for HNSCC. [ABSTRACT FROM AUTHOR]

An energy-saving control strategy for wheel loaders is proposed in this paper to address the issue of high energy consumption during their operation. The strategy is based on the intelligent identification of working stages, allowing for staged power matching and resulting in reduced energy consumption. Each work stage of the loader is identified by matching it to the main pump pressure waveform and actuator pilot pressure waveform. Using a sliding time window method, pressure waveforms from each working stage are subjected to feature extraction. A bidirectional long short-term memory neural network (BILSTM) algorithm is then used to establish an intelligent recognition model. Based on work stage identification, an energy-saving control strategy based on power matching is proposed for the shoveling stage of the loader, and the Grey Wolf optimization (GWO)-PID algorithm is utilized for control parameter tuning. Finally, the effectiveness of the energy-saving control strategy based on work stage identification is verified through experiments. The research results indicate that the BILSTM recognition model outperforms other models with a recognition accuracy of 96.1%. The optimal time window width is 0.6 s, and the proposed energy-saving control strategy achieves a fuel-saving rate of 6.81%. This method provides feasibility for reducing energy consumption in construction machinery and achieving energy-saving and carbon-reduction goals. [ABSTRACT FROM AUTHOR]

Skeletal muscle myogenesis hinges on gene regulation, meticulously orchestrated by molecular mechanisms. While the roles of transcription factors and non-coding RNAs in myogenesis are widely known, the contribution of RNA-binding proteins (RBPs) has remained unclear until now. Therefore, to investigate the functions of post-transcriptional regulators in myogenesis and uncover new functional RBPs regulating myogenesis, we employed CRISPR high-throughput RBP-KO (RBP-wide knockout) library screening. Through this approach, we successfully identified Eef1a1 as a novel regulatory factor in myogenesis. Using CRISPR knockout (CRISPRko) and CRISPR interference (CRISPRi) technologies, we successfully established cellular models for both CRISPRko and CRISPRi. Our findings demonstrated that Eef1a1 plays a crucial role in promoting proliferation in C2C12 myoblasts. Through siRNA inhibition and overexpression methods, we further elucidated the involvement of Eef1a1 in promoting proliferation and suppressing differentiation processes. RIP (RNA immunoprecipitation), miRNA pull-down, and Dual-luciferase reporter assays confirmed that miR-133a-3p targets Eef1a1. Co-transfection experiments indicated that miR-133a-3p can rescue the effect of Eef1a1 on C2C12 myoblasts. In summary, our study utilized CRISPR library high-throughput screening to unveil a novel RBP, Eef1a1, involved in regulating myogenesis. Eef1a1 promotes the proliferation of myoblasts while inhibiting the differentiation process. Additionally, it acts as an antagonist to miR-133a-3p, thus modulating the process of myogenesis. [ABSTRACT FROM AUTHOR]

This paper studies the influence of z‐pins on the impact resistance and residual tensile properties of composite large curvature components through low‐velocity impact and tension‐after‐impact tests to explore the damage mechanism. Unpinned and z‐pinned specimens with different diameters (0.3 and 0.5 mm) and spacing (3, 4, and 5 mm) were impacted at energies of 28 J and 14 J + 14 J and were stretched until failure. The theoretical models were used to predict impact dent depth and tensile strength, and the effectiveness of z‐pins and damage patterns were characterized by force‐time/displacement curves and through visual observation. The agreement between the experiments and predictions can thus validate the presented approach. Through the low‐velocity impact test, it is found that z‐pins with higher density and smaller diameter make the impact dent shallower and the surface damage less, thus showing better performance. Later, the impacted specimens mainly show delamination, explosion, breakage, and splitting after tension. During the first stage of the force‐displacement curves, since z‐pins mitigate the delamination, tensile strength shows a 29.58%–59.17% increase while in the third stage, a decrease of 3.95%–15.12% occurs due to initial damage caused by z‐pins. Highlights: Different impact energies are implemented on large curved CFRP laminates of z‐pins with different diameters and spacing to explore the damage mechanism.Low‐velocity impact and tension‐after‐impact (TAI) tests are used to simulate the centrifugal force of the blade subjected to impact and rotation after impact.Z‐pinned group with a small diameter and high density causes less damage and tensile strength in the first stage increases while decreasing in the third stage compared with the unpinned group. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction is a key factor in the occurrence of coronary artery disease and plays a vital role in the pathological development of myocardial infarction. Hypoxia contributing to endothelial cell survival and growth, metabolism and angiogenesis. HMGB1 has been identified as one of the factors involved in the regulation of vascular endothelial cell function. However, the mechanisms by which HMGB1 regulates endothelial cells under hypoxia remain unclear. Our study aimed to determine HMGB1 expression investigate the functions of HMGB1 on endothelial cell in hypoxia environment. The expression of extracellular high-mobility group box 1 (HMGB1) in cardiac endothelial cells treated with hypoxia was detected by western blot analysis. 5-Ethynyl-2′-deoxyuridine (EdU) assays and transwell assays were performed to determine the cell proliferation and migration, and flow cytometry assay was performed to evaluate the apoptosis of cardiac endothelial cell. Intracellular HMGB1 expression was upregulated in hypoxia-induced cardiac endothelial cells. HMGB1 silencing significantly promoted apoptosis and inhibited the proliferation and migration of hypoxia-induced cardiac endothelial cells. Moreover, silencing YAP1 on the basis of silencing HMGB1 can aggravate apoptosis and inhibit proliferation and migration of cardiac endothelial cells in hypoxic microenvironment. HMGB1 is up-regulated in hypoxic environment, which may be regulate the biological function of cardiac endothelial cells by YAP1, revealing that HMGB1/YAP1 may be partially involved in the protective mechanism of cardiac endothelial cells. To the best of our knowledge, this study provides a novel basis for the development of treatment methods for ischemic heart diseases. [ABSTRACT FROM AUTHOR]

In this paper, we investigate an initial value problem for a nonlinear fractional differential equation on an infinite interval. The differential operator is taken in the Hadamard sense and the nonlinear term involves two lower-order fractional derivatives of the unknown function. In order to establish the global existence criteria, we first verify that there exists a unique positive solution to an integral equation based on a class of new integral inequality. Next, we construct a locally convex space, which is metrizable and complete. On this space, applying Schäuder's fixed point theorem, we obtain the existence of at least one solution to the initial value problem. [ABSTRACT FROM AUTHOR]

In the direct laser deposition (DLD) process, it is common to employ constant processing parameters. The utilization of the constant parameters may lead to fluctuations in the dynamic evolution of the molten pool, primarily due to the intricate thermal effects involved, which will significantly impact the processing quality. To address this issue, this study proposed a closed-loop control approach that effectively modifies processing parameters in real time by targeting on the molten pool transient area. The type of the laser used in this study is a flat-top beam. Laser power, powder feeder rate, and scanning speed are the input variables of the study to control molten pool, considering the manufacturing system. The most suitable processing parameter to control the molten pool area was found to be the laser power by a set of orthogonal experiments, with a correlation coefficient of 0.706, and significance level of 0.002. Then, the dynamic response relationship between laser power and the molten pool area was mathematically characterized by a third-order transfer function model to simplify the complex physical model of the DLD process. Subsequently, a PID controller with a filtering coefficient and anti-windup compensation was chosen compared with the other controller. In the validation experiments, it was observed that the closed-loop processing group demonstrated improved stability in maintaining the molten pool transient area, with a notable decrease of 33.7% in variability compared to the open-loop processing group. As a result, the deposited layer of the closed-loop processing group exhibited a much more satisfying surface quality and heat affect zone than the open-loop group. This study established a third-order mathematical model of the dynamic molten pool and realized the optimization of deposition quality by controlling the molten pool transient area with an enhanced PID controller, providing a fundamental basis for improving the consistency of the direct laser deposition processing quality through the implementation of real-time feedback control of molten pool physics. [ABSTRACT FROM AUTHOR]

Streams may have many branches and form complex river networks. We investigate two competition patch models associated with two different river network modules, where one is a distributary stream with two branches at the downstream end, and the other is a tributary stream with two branches at the upstream end. Treating one species as resident species and the other one as mutant species, it is shown that, for each model, there exists a invasion curve such that the mutant species can invade when rare if and only if its dispersal strategy is below this curve, but the shapes of the invasion curves are different. Moreover, we show that the global dynamics of the two models can be similar or different depending on river networks. Especially, if the drift rates of the two species are equal, then the global dynamics are similar for small drift rate and different for large drift rate. Our results also confirm a conjecture in Jiang et al. (Bull Math Biol 82:131, 2020). [ABSTRACT FROM AUTHOR]

This paper mainly deals with the current status and development trends of research on the microstructure and properties of additive manufacturing formed parts. According to the laser processes and powder processing, the microstructure of the parts including morphologies, phase composition, and grain orientation is analyzed; the forming quality of the parts including hardness, wear resistance, corrosion resistance, strength, fracture toughness, residual stresses, and fatigue properties is analyzed in many ways. At the same time, we expect to find the research directions that conform to the future development trends for LAM. [ABSTRACT FROM AUTHOR]

HCC is one of the most common malignant tumors worldwide. Although traditional treatment methods have been improved in recent years, the survival rate of HCC patients has not been significantly improved. Immunotherapy has shown extremely high clinical value in a variety of tumors. In this study, we found that TUG1 could regulate the expression of PD-L1 through JAK2/STAT3 to mediate immunosuppression. Here, The expression of TUG1 and PD-L1 in HCC tissues was evaluated through analysis of databases and verified in HCC tissue and HCC cancer cells by qRT-PCR. The effect of TUG1 on tumor immune escape was detected by coculture, and cell viability was detected with a CCK8 assay. The results demonstrated that TUG1 was closely associated with anticancer immunity. TUG1 and PD-L1 were highly expressed in HCC tissues and HCC cancer cells, and high expression of TUG1 and PD-L1 was related to the poor prognosis of HCC patients. In addition, knocking down TUG1 expression could reduce PD-L1 expression and enhance the cancer cell-killing capability of T cells. Downregulating TUG1 expression could also decrease the mRNA and protein expression of JAK2 and STAT3. To sum up, TUG1 and PD-L1 are overexpressed in patients with liver cancer and are related to the poor prognosis of these patients. Silencing TUG1 expression reduced the mRNA and protein expression of PD-L1 by affecting the JAK2/STAT3 pathway. [ABSTRACT FROM AUTHOR]

HCC is one of the most common malignant tumors worldwide. Although traditional treatment methods have been improved in recent years, the survival rate of HCC patients has not been significantly improved. Immunotherapy has shown extremely high clinical value in a variety of tumors. In this study, we found that TUG1 could regulate the expression of PD-L1 through JAK2/STAT3 to mediate immunosuppression. Here, The expression of TUG1 and PD-L1 in HCC tissues was evaluated through analysis of databases and verified in HCC tissue and HCC cancer cells by qRT-PCR. The effect of TUG1 on tumor immune escape was detected by coculture, and cell viability was detected with a CCK8 assay. The results demonstrated that TUG1 was closely associated with anticancer immunity. TUG1 and PD-L1 were highly expressed in HCC tissues and HCC cancer cells, and high expression of TUG1 and PD-L1 was related to the poor prognosis of HCC patients. In addition, knocking down TUG1 expression could reduce PD-L1 expression and enhance the cancer cell-killing capability of T cells. Downregulating TUG1 expression could also decrease the mRNA and protein expression of JAK2 and STAT3. To sum up, TUG1 and PD-L1 are overexpressed in patients with liver cancer and are related to the poor prognosis of these patients. Silencing TUG1 expression reduced the mRNA and protein expression of PD-L1 by affecting the JAK2/STAT3 pathway. [ABSTRACT FROM AUTHOR]

This paper proposes a low-in-plane damage ZPI (Z-pin pre-hole insertion) process. The delamination growth behavior and the influence of Z-pin insertion density on the mode I interlaminar fracture toughness of laminate was explored experimentally and numerically. Meanwhile, Z-pin pull-out and shear tests were conducted in order to provide accurate data for the DCB simulation test. What's more, an infinite-focus microscope was used to scan the specimen's defect caused by the ZPI process. It can be found that the ZPI process can lead to less Z-pin inclination, fibre breaking, and crack initiation at the bonded interface. The DCB test results show that the load-displacement curve can be distinguished into four stages for the pinned specimen. In addition, a specimen pinned with a higher Z-pin volume fraction to more suitable for increasing the G IC . The simulation results show that the simulated maximum load and the G IC of the specimen are 286.63 N and 940.06 J·m−2, with a 0.56% and 10.10% error from the experimental result, indicating that the proposed FE model is validated by comparing the predictions with the experimental results. These results can provide some guidance for fabricating the reinforced laminates via the ZPI process. [ABSTRACT FROM AUTHOR]

Background: Porcine fetal fibroblasts (PFFs) are important donor cells for generating genetically modified pigs, but the transfection efficiencies of PFFs are often unsatisfactory especially when large-size vectors are to be delivered. In this study, we aimed to optimize the transfection conditions for delivery of a large-size vector in PFFs using Lonza 4D-Nucleofector™ vessels and strips. Methods: We firstly delivered a 13 kb Cas9-EGFP and a 3.5 kb pMAX-GFP vector into PFFs via 7 programs recommended by the Lonza basic protocol. We then tested 6 customized dual-electroporation programs for delivering the 13 kb plasmid into PFFs. In addition, we screened potential alternative electroporation buffers to the Nucleofector™ P3 solution. Finally, three CRISPR/Cas9-sgRNAs targeting Rosa26, H11, and Cep112 loci were delivered into PFFs with different single and dual-electroporation programs. Results: Notably lower transfection efficiencies were observed when delivering the 13 kb vector than delivering the 3.5 kb vector in PFFs via the single-electroporation programs. The customized dual-electroporation program FF-113 + CA-137 exhibited higher transfection efficiencies than any of the single-electroporation programs using vessels (98.1%) or strips (89.1%) with acceptable survival rates for the 13 kb vector. Entranster-E buffer generated similar transfection efficiencies and 24-hour survival rates to those from the P3 solution, thus can be used as an alternative electroporation buffer. In the genome-editing experiments, the FF-113 + CA-137 and CA-137 + CA-137 programs showed significantly superior (P < 0.01) efficiencies to ones from the single-electroporation programs in vessels and strips. Entranster-E buffer produced higher indel efficiencies than the P3 buffer. Conclusions: We markedly increased the delivery efficiencies for a large vector via customized dual-electroporation programs using Lonza 4D-Nucleofector™ system, and Entranster-E buffer can be used as an alternative electroporation buffer to Nucleofector™ P3 buffer. [ABSTRACT FROM AUTHOR]

Excessive water and water deficit are two important factors that limit agricultural development worldwide. However, the impact of waterlogging on winter wheat yield on a large scale, compared with drought caused by water deficit, remains unclear. In this study, we assessed the waterlogging damage to winter wheat yield using the downscaled and fused TRMM 3B42 from 1998 to 2014. First, we downscaled the TRMM 3B42 with area-to-point kriging (APK) and fused it with rain gauge measurements using geographically weighted regression kriging (GWRK). Then, we calculated the accumulated number of rainy days (ARD) of different continuous rain processes (CRPs) with durations ranging from 5 to 15 days as a waterlogging indicator. A quadratic polynomial model was used to fit the yield change rate (YCR) and the waterlogging indicator, and the waterlogging levels (mild, moderate, and severe) based on the estimated YCR from the optimal model were determined. Our results showed that downscaling the TRMM 3B42 using APK improved the limited accuracy, while GWRK fusion significantly increased the precision of quantitative indicators, such as R (from 0.67 to 0.84), and the detectability of precipitation events, such as the probability of detection (POD) (from 0.60 to 0.78). Furthermore, we found that 67% of the variation in the YCR could be explained by the ARD of a CRP of 11 days, followed by the ARD of a CRP of 13 days (R2 of 0.65). During the typical wet growing season of 2001–2002, the percentages of mild, moderate, and severe waterlogged pixels were 5.72%, 2.00%, and 0.63%, respectively. Long time series waterlogging spatial mapping can clearly show the distribution and degree of waterlogging, providing a basis for policymakers to carry out waterlogging disaster prevention and mitigation strategies. [ABSTRACT FROM AUTHOR]

This study investigates variation in adolescent attitudes regarding dating violence under different conditions, the association of these conditional attitudes with subsequent adolescent relationship abuse (ARA), and youth and parent-reported characteristics associated with youth attitudes. The sample consists of 607 youth, as a subset from those who responded to a nationally representative longitudinal survey of dating violence. A latent class analysis identified three profiles of attitudinal patterns: No Tolerance for Hitting Partners (NT), Some Tolerance for Hitting Partners (ST), and High Tolerance for Hitting Partners (HT). The HT profile predicted subsequent physical (compared to the NT profile), sexual ARA perpetration (compared to both the NT and the ST profiles), and physical ARA victimization (compared to the NT profile). The ST profile predicted subsequent psychological ARA perpetration and victimization (compare to the NT profile). Results inform youth dating violence prevention programs to reduce ARA and intimate partner violence by changing youth attitudes toward dating violence. [ABSTRACT FROM AUTHOR]

Cytosine base editors (CBEs) and adenine base editors (ABEs) are recently developed CRISPR-mediated genome-editing tools that do not introduce double-strand breaks. In this study, five ABEs, ABE7.10, ABEmax, NG-ABEmax, ABE8e and NG-ABE8e, were used to generate A-to-G (T-to-C) conversions in five genome loci in porcine fetal fibroblasts (PFFs). Variable yet appreciable editing efficiencies and variable activity windows were observed in these targeting regions via these five editors. The strategy of two sgRNAs in one vector exhibited superior editing efficiency to that of using two separate sgRNA expression vectors. ABE-mediated start-codon mutation in APOE silenced its expression of protein and, unexpectedly, eliminated the vast majority of its mRNA. No off-target DNA site was detected for these editors. Substantial off-target RNA events were present in the ABE-edited cells, but no KEGG pathway was found to be significantly enriched. Our study supports that ABEs are powerful tools for A-to-G (T-to-C) point-mutation modification in porcine cells. [ABSTRACT FROM AUTHOR]

This paper mainly discusses the current research status and development trend of on-line monitoring technology for laser additive manufacturing. We have analyzed various on-line monitoring techniques for laser additive manufacturing based on visual imaging, temperature field, spectral analysis, and acoustic principles. Numerous analyses are performed on the monitored objects, the melt pool, including melt pool temperature and morphology dimensions, and the formed parts, including microstructure and properties. The analysis of on-line monitoring techniques for laser additive manufacturing is expected to find the research directions that meet future development trends. [ABSTRACT FROM AUTHOR]

Novel thermoplastic fluorinated polyacrylate films possessing excellent mechanical performance are prepared by emulsion polymerization latex using adjustable amphiphilic star macro‐reversible addition‐fragmentation chain‐transfer (macro‐RAFT) agent as surfactants in this work. First, star macro‐RAFT agent equipped with six amphiphilic arms is synthesized via two‐step RAFT polymerization of acrylic acid (AA) and 2,2,2‐trifluoroethyl acrylate (TFEA) in the presence of hexa‐functional RAFT agents. The surface activities of the as‐synthesized amphiphilic star macro‐RAFT agents in aqueous solutions are studied. Subsequently, various fluorinated polyacrylate latexes are obtained by conducting emulsion polymerization of 2,2,3,4,4,4‐hexafluorobutyl acrylate (HFBA) and butyl acrylate (BA) using the amphiphilic star macro‐RAFT agents as both RAFT agents and surfactants. The latex particle morphologies are studied by transmission electron microscope (TEM) and particle size is measured by dynamic light scattering (DLS). The effects of PAA segment length, HFBA/BA mole ratio, and TFEA segment length on the surface morphologies of the fluorinated polyacrylate films are illustrated by investigating the surface properties using water contact angle test and atomic force microscopy (AFM). Finally, the elastomeric films obtained by directly casting the prepared fluorinated polyacrylate latexes show excellent comprehensive properties such as tensile strength over 4 MPa, elongation at break ≈700%, permanent deformation below 25%. Water absorption test is also provided as a reference. [ABSTRACT FROM AUTHOR]

Research question: More than 100 variants have been identified in the TUBB8 gene, which account for approximately 30% of infertile women with oocyte maturation defects. But what is the correlation between the highly phenotypic diversity and genetic variability? Are there other variants in TUBB8 related to female infertility? Design: TUBB8 resequencing was performed in 80 female subjects who were experiencing infertility and were seeking treatment with assisted reproductive technologies (ART), or had ever experienced ART failure due to oocyte maturation defects. All variants were evaluated with pedigree analysis, population frequency, in-silico analysis and molecular modelling. The effects of the variants on oocytes/arrested embryos were assessed by morphological observations, immunostaining, embryo biopsies and chromosome euploidy analysis. Results: Nine missense variants and two frameshift variants from an additional 15 families were identified, including four novel variants and seven previously reported recurrent variants. These TUBB8 variants were related to highly variable phenotypes, including abnormalities in oocyte maturation or morphology, fertilization failure, embryonic development abnormalities and implantation failure. Also further clarified were the incomplete penetrance of heterozygous p.E108K, the likely benign significance of heterozygous p.A313V and the clinical effect of a novel variant of p.R380C. Conclusions: This study significantly expands the variant spectrum of the TUBB8 gene and, together with the available findings on TUBB8 variants and female infertility, will potentially facilitate the genetic counselling of infertile women in future. [ABSTRACT FROM AUTHOR]

Stemming intimate partner violence among adults demands earlier education and skill-building supportive of healthy youth and young adult dating relationships. The current U.S.-based study examines a spectrum of youth and young adult relationship dynamics (RDs), inclusive of abusive interactions. In a nationally representative cohort of youth aged 10–18 at baseline and one parent or caregiver, survey responses regarding RDs from 618 participants ages 15–23 at wave 5 follow-up were analyzed. Latent class analysis of four positive dynamics, six problematic dynamics, and three scales of adolescent relationship abuse (ARA) were estimated, yielding four latent profiles of dating RDs. Relationships characterized by Unhealthy and Intense RDs both exhibited high probability of ARA but differed from each other in terms of other positive and problematic dynamics. Relationships characterized by Disengaged RDs had lower probability of ARA but elevated probability of awkward communications, negative feelings, social liability, and other challenging dynamics. Several baseline covariates were significantly associated with profiles of dating RDs approximately 5 years later. Younger participants were more likely to subsequently fall in an Intense or Disengaged RDs profile, as were participants with baseline emotional health problems. Further, classification in the Unhealthy RDs profile was less likely for participants reporting a better baseline relationship with their parents and more likely for those exposed to violence in childhood. These findings suggest that in addition to developmental maturity, youth and young adults would benefit from closer investigation and processing of past emotional and relational issues and traumas to foster healthier dating relationships. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is a chronic non-communicable disease. It is a metabolic syndrome (MS) in the liver. Menopause is a physiological phenomenon of women due to the decline of ovarian function, which is characterized by the deterioration of hypothalamic-pituitary function. Clinical and epidemiological studies have shown that the incidence trend of NAFLD has gender differences and is related to metabolic parameters such as glucose, lipids, and blood uric acid. The incidence of NAFLD in premenopausal women is lower than that in males, while the incidence of NAFLD in postmenopausal women gradually increases to the same as that in males. The mechanism may be mainly related to the changes of sex hormones in postmenopausal women (mainly the decrease of estrogen). The changes of sex hormones such as the decreased levels of estrogen and sex hormone binding globulin (SHBG) and the relatively increased level of androgen can increase the incidence of MS components such as abdominal obesity, abnormal blood lipid metabolism and insulin resistance (IR), making menopause an important independent risk factor for NAFLD in women. Estrogen, androgen receptor antagonists and phytoestrogens can improve hepatic steatosis and IR through many ways, reduce the severity of NAFLD and delay its progression to liver fibrosis, which have certain therapeutic significance for postmenopausal women with NAFLD, but also have some limitations. This paper reviews the research progress in the relationship between menopause and NAFLD in recent years, so as to provide ideas and reference for the prevention and treatment of NAFLD in postmenopausal women. [ABSTRACT FROM AUTHOR]

Dynamically encircling the exceptional point (EP) of an anti‐parity‐time (anti‐PT) symmetric system can achieve chiral mode switching between symmetry‐broken eigenmodes, which is especially important for developing nanophotonic devices. However, the realization of anti‐PT‐symmetric systems on a chip still remains significantly challenging as precisely controlling the parameters of nanophotonic structures is difficult. Herein, a novel anti‐PT‐symmetric system is designed and constructed on a silicon‐on‐insulator chip by taking advantage of subwavelength gratings to help engineer nanophotonic structures. Consequently, on‐chip chiral switching between symmetry‐broken eigenmodes is experimentally realized by dynamically encircling the EP in parametric space of the proposed anti‐PT‐symmetric system. Moreover, the achieved chiral mode switching exhibits high output power ratios (≥ 6.4 dB) at 1550 nm, wide‐band response that covers C‐band completely, and great thermal stability up to 90 °C, which indicate desirable performance features for practical applications in optical communication. This study paves an avenue for realizing on‐chip chiral switching between symmetry‐broken modes, which shows great promise for developing nanophotonic devices, such as optical switching, logic gates, and isolators, in optical telecommunication bands. [ABSTRACT FROM AUTHOR]

Exabytes of data are generated daily by humans, leading to the growing needs for new efforts in dealing with the grand challenges for multi-label learning brought by big data. For example, extreme multi-label classification is an active and rapidly growing research area that deals with classification tasks with extremely large number of classes or labels; utilizing massive data with limited supervision to build a multi-label classification model becomes valuable for practical applications, etc. Besides these, there are tremendous efforts on how to harvest the strong learning capability of deep learning to better capture the label dependencies in multi-label learning, which is the key for deep learning to address real-world classification tasks. However, it is noted that there have been a lack of systemic studies that focus explicitly on analyzing the emerging trends and new challenges of multi-label learning in the era of big data. It is imperative to call for a comprehensive survey to fulfil this mission and delineate future research directions and new applications. [ABSTRACT FROM AUTHOR]

• A powder-scale high precision multi-physics model is developed to depict the DED-LB process. • The single-track Inconel 718 alloy DED-LB experiments are used to validate the powder scale model and GPR model results. • The physically based-data driven agent model is developed to rapidly and accurately predict the geometry and dilution rate. • The DED-LB PS-ML model for optimal process maps is developed to achieve process parameter optimization using a comparatively small accurate data. The major challenge faced is the definition of optimal process variables for rich quality of fabricated parts in laser-based directed energy deposition (DED-LB) processes. However, predicting the optimal process scheme using machine learning models is still challenging owing to the need for a large amount of training experimental data with high costs in DED-LB. In view of this, a physical simulation (PS)-machine learning (ML) model using a relatively small accurate data set of 31 simulation data for optimal process schemes is proposed in DED-LB process in this study. Firstly, a powder-scale high precision phenomenon model incorporating the mass transfer, phase transformations and heat transfer and using Lagrangian particle model to add mass is developed to depict the DED-LB process. Then, a Gaussian process regression (GPR) agent model is established to rapidly and accurately predict the geometry and dilution rate of deposition tracks under different manufacturing parameters based on the high precision simulation results. Finally, a PS-ML model for process parameter optimization is developed using the particle swarm algorithm (PSO), and the optimized parameters are experimentally validated. The results show that the developed powder-scale model and GPR model results are consistent with the Inconel 718 alloy experimental results. The proposed PS-ML model can increase the accuracy of the ML models even with a small simulation data set. None of PS-ML model optimization results has a relative error of more than 3% to the experimental results, and the dilution rate is reduced by up to 61.66% compared to the experimental design parameters without optimization. The proposed physical simulation-machine learning model in this study enables inexpensive and accurate optimization of DED-LB process parameters. [ABSTRACT FROM AUTHOR]

The influence of varying SiC p on the mesoscopic characteristics, microstructural evolution, microhardness, frictional mechanisms, and corrosion resistance behavior of laser-based directed energy deposition Ni60-SiC p composite coatings was investigated. Coatings reinforced with varying SiC p , the innovative concept of the ''Temperature-SiC p joint effect'' mechanism was proposed. The microstructure was progressively refined due to the SiC p , while microhardness was affected by the solid solution strengthening and diffusion strengthening effects of high SiC p. Furthermore, based on wear scar morphologies, wear scar EDS analysis, and wear mechanism modeling, the frictional mechanisms were elucidated. Simultaneously, a clear understanding of the relationship between SiC p and corrosion behavior were established. It is evident that the analysis of SiC p reinforcement content in composite holds significant guiding significance. [Display omitted] • The effect of SiC p on the mesoscopic characteristics, microstructure evolution, and friction corrosion resistance. • Temperature-SiC p joint effect mechanism is proposed to clarify mesoscopic characteristics. • The microstructure of both the surface and cross-section has been refined. • The Ni60-25SiC p coating demonstrates the best friction and corrosion resistance. [ABSTRACT FROM AUTHOR]

• Leaf inclination angle (LIA) was first measured at three vertical layers during the growth period. • 1D canopy reflectance simulation with spherical leaf angle distribution (LAD) only holds before the jointing stage. • Vertical variation of leaf spectra affects canopy reflectance during the maturation stage. • Angularly-averaged clumping index (CI) slightly improves the 1D canopy reflectance simulations. • Leaf inclination angle (LIA) profile can remarkably improve the 1D canopy reflectance simulations. Physical model simulations have been widely utilized to simulate the reflectance of vegetation canopies. Such simulations can be used to estimate key biochemical and physical vegetation parameters, such as leaf chlorophyll content (LCC), leaf area index (LAI), and leaf inclination angle (LIA) from remotely sensed data via model inversion. In simulations, field crops are typically regarded as one-dimensional (1D) vegetation canopies with constant leaf properties in the vertical direction and across the growing season. We investigated the seasonal effects of these two simplifications, 1D canopy structure, and vertically constant leaf properties, on canopy reflectance simulations in a rice field using in situ measurements and the 3D discrete anisotropic radiative transfer model (DART). We also developed a new methodology for reconstructing 3D crop canopy architecture, which was validated using measurements of gap fraction and canopy reflectance. Our results revealed that the 1D canopy assumption only holds during the early stage of the growing season, then leaf clumping affects canopy reflectance from the jointing stage onwards. Consideration of the 3D canopy structure and its seasonal variation significantly reduced the deviation between simulated and measured canopy reflectance in the green and near-infrared wavelengths when compared to the typical 1D canopy assumption and produced the closest multi-angular distribution pattern to the measurements. The vertical heterogeneity of leaf spectra affected canopy reflectance weakly during the maturation stage when senescence started from the bottom of the canopy. Consideration of seasonal and vertical variation in LIAs significantly improved the results of 1D canopy reflectance simulations, including the multi-angular distribution patterns. In contrast, the directionally-averaged clumping index (CI) only slightly improved the 1D canopy reflectance simulation. To summarize, these findings can be used to reduce the simulation bias of canopy reflectance and improve the retrieval accuracy of key vegetation parameters in crop canopies at the seasonal scale. [ABSTRACT FROM AUTHOR]

When patent foramen ovale (PFO) combines with the prominent Eustachian valve or Chiari network (EV/CN), contrast transthoracic echocardiography (cTTE) may miss the diagnosis of PFO. We sought to determine the characteristics of right-to-left shunt (RLS) in PFO patients with prominent EV/CN on cTTE and identify the causal factors of missed diagnosis. We consecutively enrolled 98 patients who suffered from PFO-related stroke and with prominent EV/CN. All patients were divided into the delayed and non-delayed groups according to the characteristics of RLS on cTTE. The characteristics of RLS were compared with those of 42 intrapulmonary shunt patients. The anatomical characteristics of PFO and EV/CN were analyzed in the 98 PFO patients. Upon cTTE, significantly delayed occurrence and longer duration of the RLS in the delayed group were found both at rest and during the Valsalva maneuver, similar to the intrapulmonary shunt. Multivariate logistic analysis revealed that the length of EV/CN (>19 mm) and the diameter of PFO at the left atrium aspect (<1.2 mm) were high-risk factors for missed diagnosis. In conclusion, RLS showed delayed emergence and disappearance in some of the PFO patients with prominent EV/CN. The length of EV/CN and the diameter of PFO may have been related to the missed diagnosis of PFO. [ABSTRACT FROM AUTHOR]

Structural variations (SVs) are important DNA polymorphisms that contribute to genetic diversity and evolution in humans, animals, and plants. In this study, we present a novel swine SV dataset of 79,919 deletions, 23,638 duplications, and 9333 inversions with average sequence depths of 24.1× from 24 varieties of worldwide pig populations, encompassing 305 individuals. Genotypes of SVs, particularly deletions, can accurately group individuals based on their population identity. We showed that exon‐covering deletions were subject to negative selection. Fixation index and differential allele frequency analysis identified highly differentiated SVs between European and Asian indigenous pigs, including deletions in NR6A1 and PLAG1, which are significantly associated with vertebrate numbers and growth performances, respectively. The growth‐enhancing allele at the deletion in PLAG1 was shared by European commercial pigs and Northern Chinese indigenous pigs including Laiwu and Min pigs, suggesting potential introgression from European commercial breeds into Chinese indigenous breeds. Moreover, we uncovered highly differentiated SVs in 139 genes between domesticated pigs and wild boars in Asia, temperature and altitude adaptation‐associated SVs in 41 genes, and population‐specific SVs in 718 genes. This study provides novel insights into the role of porcine SVs in domestication, environmental adaptation, and breed formation. [ABSTRACT FROM AUTHOR]

Surface-enhanced Raman scattering (SERS) provides an unprecedented opportunity for fingerprinting identification and trace-level detection in chemistry, biomedicine, materials, and so on. Although great efforts have been devoted to fabricating sensitive plasmonic nanomaterials, it is still challenging to batch-produce a SERS substrate with high sensitivity, good reproducibility, and perfect recyclability. Here, we describe a facile fabrication of three-dimensional (3D) hierarchical Au/CuS nanocomposites, in which high-density Au nanotips enable highly SERS-active sensing, and the well-defined microflower (MF) geometry produces perfect signal reproducibility (RSD < 5%) for large laser spot excitations (>50 μm2), which is particularly suitable for practical on-site detection with a handheld Raman spectrometer. In addition, a self-cleaning ability of this Au/CuS Schottky junction photocatalyst under sunlight irradiation allows complete removal of the adsorbed analytes, realizing perfect regeneration of the SERS substrates over many cycles. The mass-production, ultra-sensitive, high-reproducibility, and fast-recyclability features of hierarchical Au/CuS MFs greatly facilitate cost-effective and field SERS detection of trace analytes in practice. [ABSTRACT FROM AUTHOR]

This paper investigates global dynamics of an infection age-space structured cholera model. The model describes the vibrio cholerae transmission in human population, where infection-age structure of vibrio cholerae and infectious individuals are incorporated to measure the infectivity during the different stage of disease transmission. The model is described by reaction–diffusion models involving the spatial dispersal of vibrios and the mobility of human populations in the same domain Ω ⊂ ℝn. We first give the well-posedness of the model by converting the model to a reaction–diffusion model and two Volterra integral equations and obtain two constant equilibria. Our result suggest that the basic reproduction number determines the dichotomy of disease persistence and extinction, which is achieved by studying the local stability of equilibria, disease persistence and global attractivity of equilibria. [ABSTRACT FROM AUTHOR]

Image scene classification aiming to assign specific semantic labels for each image is vitally important for the applications of remote sensing (RS) data. In real world, since the observation environment is open and dynamic, RS images are collected sequentially and the numbers of images and classes grow rapidly over time. Most existing scene classification methods are offline learning algorithms, which are inefficient and unscalable for this scenario. In this article, an incremental learning with open-set recognition (ILOSR) framework is proposed for RS image scene classification in the open and dynamic environment, which can identify the unknown classes from a stream of data and learn these new classes incrementally. Specifically, a controllable convex hull-based exemplar selection strategy is designed to address the catastrophic forgetting issue in incremental learning, which can reduce training time and memory footprint effectively. In addition, a new loss function based on prototype learning and uncertainty measurement is proposed for OSR to enhance the interclass discrimination and intraclass compactness of the learned deep features. Experimental results on real RS datasets demonstrate that the proposed method can not only outperform the state-of-the-art approaches on offline classification, incremental learning, and OSR problem separately but also achieve better and more stable performance in the experiments for ILOSR. [ABSTRACT FROM AUTHOR]

To investigate the influence of modification of ceramic fillers on the dielectric properties of polymer-based composites, TiO 2 and core-shell structured TiO 2 @HfO 2 nanowires were synthesized, and investigated in this study. TiO 2 nanowires/polyvinylidene fluoride (PVDF) and TiO 2 @HfO 2 nanowires/PVDF nanocomposites were prepared using the solution casting method. The experimental results showed that the TiO 2 @HfO 2 nanowires/PVDF composites had improved dielectric properties compared with that of the TiO 2 nanowires/PVDF composites. Owing to the enhanced interfacial polarisation by the multilevel interface, the composites with 10 wt % TiO 2 @HfO 2 nanowires achieved the highest permittivity of 12.56 at 1 kHz, which was enhanced by ∼72% compared to the PVDF matrix. The electric field was evenly distributed by building the fillers with a gradient dielectric constant. The characteristic breakdown strength of the composite with 5 wt % TiO 2 @HfO 2 reached 377.76 kV/mm, compared with that of 334.37 kV/mm for the composite with 5 wt % TiO 2 nanowires. This study initiated a novel strategy for preparing dielectrics with high dielectric constant and improved breakdown strength. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common cancers threatening women's health. Our previous study found that silibinin induced the death of MCF-7 and MDA-MB-231 human breast cancer cells. We noticed that silibinin-induced cell damage was accompanied by morphological changes, including the increased cell aspect ratio (cell length/width) and decreased cell area. Besides, the cytoskeleton is also destroyed in cells treated with silibinin. YAP/TAZ, a mechanical signal sensor interacted with extracellular pressure, cell adhesion area and cytoskeleton, is also closely associated with cell survival, proliferation and migration. Thus, the involvement of YAP/TAZ in the cytotoxicity of silibinin in breast cancer cells has attracted our interests. Excitingly, we find that silibinin inhibits the nuclear translocation of YAP/TAZ in MCF-7 and MDA-MB-231 cells, and reduces the mRNA expressions of YAP/TAZ target genes, ACVR1 , MnSOD and ANKRD. More importantly, expression of YAP1 gene is negatively correlated with the survival of the patients with breast cancers. Molecular docking analysis reveals high probabilities for binding of silibinin to the proteins in the YAP pathways. DARTS and CETSA results confirm the binding abilities of silibinin to YAP and LATS. Inhibiting YAP pathway either by addition of verteporfin, an inhibitor of YAP/TAZ-TEAD, or by transfection of si-RNAs targeting YAP or TAZ further enhances silibinin-induced cell damage. While enhancing YAP activity by silencing LATS1/2 or overexpressing YAPS127/397A, an active form of YAP, attenuates silibinin-induced cell damage. These findings demonstrate that inhibition of the YAP/TAZ pathway contributes to cytotoxicity of silibinin in breast cancers, shedding lights on YAP/TAZ-targeted cancer therapies. [ABSTRACT FROM AUTHOR]

• Proposes a multi-stage determination method for excavator working points that considers engine fuel consumption, hydraulic pump efficiency, and load fluctuation, overcoming limitations of traditional methods. • Introduces a comprehensive evaluation model for working point determination that integrates fuel consumption, hydraulic pump efficiency, and load variability, offering a more holistic approach. • Utilizes experimental data to inform the determination of engine working points, ensuring practical relevance and applicability. • Employs weight parameters to adjust the importance of fuel consumption and load fluctuation in the working point optimization process, allowing for tailored engine performance improvement under varying operational needs. In view of the problem that the traditional working point determination method only considers the engine fuel consumption and does not consider the hydraulic pump efficiency and load fluctuation in the process of the working point stability control of an excavator engine, a simple and feasible, experimental data-driven, multi-stage determination method of excavator working point based on the comprehensive evaluation model is proposed. In this paper, the comprehensive evaluation model of working point torque with weight parameters is established at different working stages under the rated speed in a phased way. The results show that this method can determine the working point torque at different working stages, and reduce engine fuel consumption and load fluctuation based on ensuring the efficiency of the hydraulic pump. The lowest engine fuel consumption can be reduced by 7.09%, and the lowest load fluctuation can be reduced by 17.8%. In addition, by modifying the weight parameters, we can emphasize the fuel consumption and load fluctuation of the engine according to their importance, to achieve the determination of working points under different requirements. This approach also provides a new idea for optimizing the working point of construction machinery. [ABSTRACT FROM AUTHOR]

• N -doped graphene is prepared from mechanical exfoliation process and nitrogen plasma irradiation. • MnO 2 nanoflakes are successfully electrodeposited on hydrothermal prepared NiCo 2 O 4 nanowires. • Asymmetric supercapacitor based on NiCo 2 O 4 @MnO 2 nanowires and N -doped graphene exhibits competitive performance. The design and fabrication of scalable energy storage systems are crucial for portable applications, demanding advanced materials through large-scale and facile processing. In this report, an asymmetric solid-state pseudocapacitor (ASPC) is assembled using a core–shell NiCo 2 O 4 @MnO 2 composite and solution-processed nitrogen-doped graphene (N -GP) as the positive and negative electrodes, respectively. With interconnected porous structures, the electrodes based on N -GP and NiCo 2 O 4 @MnO 2 offer high specific capacitance and rate capability, broad operation voltage, and a binder-free design with no added conductive agent. With these benefits, the ASPC with a PVA-KOH electrolyte exhibits a specific capacitance of 103.3F g−1 at 1 A/g and exceptional energy density of 36.73 Wh kg−1 at a power density of 792 W kg−1. In addition, the specific capacitance retention reaches 90.9 % after 5000 cycles, indicating excellent cycling stability. In the broader context of solid-state supercapacitors based on solution-processed graphene, this ASPC exhibits highly competitive performance, establishing it as a promising candidate for advanced energy storage. [ABSTRACT FROM AUTHOR]

Cancer is still one of the major health issues faced by human beings today. Various nanomaterials have been designed to treat tumors and have made great progress. Herein, we used amino-functionalized metal organic framework (UiO-66-NH2) as superior templates and successfully synthesized the UiO-66-NH2@Aushell composite nanoparticles (UA) with high loading capacity and excellent photothermal properties through a simple and gentle method. In addition, due to the rich pore structure and excellent biocompatibility of the as-prepared composite nanoparticles, the hydrophobic NO donor BNN6 (N,N′-Di-sec-butyl-N,N′-dinitroso-1, 4-phenylenediamine) molecule was efficiently delivered. Based on the phenomenon where BNN6 molecules can decompose and release NO at high temperature, when UiO-66-NH2@Aushell-BNN6 composite nanoparticles (UA-BNN6) entered tumor cells and were irradiated by NIR, the porous gold nanoshells on the surface of composite nanoparticles induced an increase in temperature through the photothermal conversion process and promoted the decomposition of BNN6 molecules, releasing high concentration of NO, thus efficiently killing HeLa cells through the synergistic effect of NO-photothermal therapy. This effective, precise and safe treatment strategy controlled by NIR laser irradiation represents a promising alternative in the field of cancer treatment. [ABSTRACT FROM AUTHOR]

SnSe is considered as a thermoelectric material with great potential and advantages due to the record of high thermoelectric figure of merit (ZT) of 2.6 ​at 923 ​K in single crystals. However, it is difficult to use single crystal SnSe in practice due to its poor mechanical properties and high manufacturing costs. Meanwhile, the polycrystalline SnSe also is also not suitable for applications due to its much lower thermoelectric performance compared with single crystal SnSe. Therefore, improving the thermoelectric properties of polycrystalline SnSe has become a hot research topic. In this paper, AgSnSe 2 doped into SnSe to increase the carrier density of the system and thus improve its thermoelectric properties. It is found that the addition of AgSnSe 2 can effectively improve the thermoelectric performance of polycrystalline SnSe. A peak ZT of 0.81 was obtained at 713 ​K for (SnSe) 0.95 (AgSnSe 2) 0.025 , which is 305% higher than that of the undoped one. This reveals that AgSnSe 2 -doped SnSe alloy may become a thermoelectric material system with great application potential and significance. [Display omitted] • Doping AgSnSe 2 compound into SnSe is a new method for obtaining high performance SnSe based thermoelectric materials. • A ZT value of 0.81 ​at 713 ​K was obtained for SPS synthesized (SnSe) 0.95 (AgSnSe 2) 0.025 alloy. • The peak ZT value of (SnSe) 0.95 (AgSnSe 2) 0.025 is 305% higher than that of undoped SnSe. [ABSTRACT FROM AUTHOR]

Reasonable evaluation and prediction of squeezing condition to avoid large deformation disaster in tunnels have been an important research issue. In order to accurately and rapidly predict the large deformation under complex geological conditions, this paper proposes a classification and prediction method for quick identification of large deformation in tunnel construction stage in a case study of Muzhailing Tunnel. Previous prediction methods of large deformation are usually based on the stages of geological survey and engineering design, and there are great difficulties in obtaining some prediction indexes in soft and fractured strata, such as uniaxial compressive strength. In this paper, the nonlinear deformation behaviors of surrounding rock were analyzed. The geo-stress condition, strata occurrence, rock strength, rock intactness and groundwater condition were chosen as evaluation indexes (including eight sub-indexes). The classification of large deformation was carried out based on the deformation statistics in Muzhailing Tunnel. And the fuzzy prediction was conducted and compared with other methods in engineering. The comparison results show that the new method has higher accuracy and applicability in predicting the large deformation of weak rock mass. This study provides a new approach for rapid identification and prediction of large deformation in tunnel construction stage. [ABSTRACT FROM AUTHOR]

Background: Although the prognostic outcomes of liver cancer (LC) cases have improved with the advancement in diagnostic technology and treatment methods, the transferability and recurrence of HCC and the 5-year and 10-year survival rates of patients have remained unsatisfactory. As a result, there is a need for more accurate diagnostic indicators that can detect liver cancer early, effectively improving the prognosis of patients. Whole-genome sequencing (WGS) revealed that circ-ZEB1 and PIK3CA are highly expressed in HCC tissues, whereas miR-199a-3p is significantly downregulated in HCC. Multiple databases search and biological analysis revealed that elevated expression of circ-ZEB1 and PIK3CA was related to poor prognosis of HCC. In vitro and in vivo studies revealed that upregulated levels of PIK3CA and circ-ZEB1 were closely associated with HCC proliferation and apoptosis. Based on these results, we believe that circ-ZEB1 and PIK3CA could be used as biomarkers to diagnose and treat patients with HCC. More importantly, circ-ZEB1 can promotes the expression of PIK3CA by silencing miR-199a-3p and affecting the progression of HCC. Methods and results: Postoperative specimens from 56 patients with HCC who had not undergone chemotherapy from 2015 to 2018 were collected from the Department of Hepatobiliary Surgery, Second Affiliated Hospital of Nanchang University. WGS revealed differential expression of genes in HCC. Furthermore, RT-qPCR detected the expression of circ-ZEB1, miR-199a-3p, and PIK3CA in HCC tissues. MTT, EdU, and plate cloning experiments were conducted to detect cell proliferation, whereas flow cytometry analysis was used to detect apoptosis. FISH was used to co-localize circ-ZEB1 and miR-199a-3p, and biotin-coupled probe pull-down assay was used to detect the specific binding of circ-ZEB1 and miR-199a-3p. The dual-luciferase report assay detected the association of miR-199a-3p with PIK3CA. Western blotting was used to study the expression of PIK3CA protein. Circ-ZEB1 and PIK3CA were upregulated in HCC and predicted a poor prognosis. MiR-199a-3p showed low expression in HCC, whereas downregulation of circ-ZEB1 reduced HCC cell proliferation and promoted cell apoptosis. MiR-199a-3p blocked the effect of circ-ZEB1 on HCC. Circ-ZEB1 served as a biomarker of HCC. Circ-ZEB1 promoted the expression of PIK3CA by silencing miR-199a-3p to affect the progress of HCC. Conclusions: Circ-ZEB1 promoted the expression of PIK3CA by depleting miR-199a-3p, thereby affecting HCC proliferation and apoptosis. [ABSTRACT FROM AUTHOR]

LncRNAs are widely involved in various biological processes of plants. Recent evidences indicated that lncRNAs could act as competing endogenous RNAs (ceRNAs) to adsorb complementary miRNAs in a type of target mimicry, thereby indirectly regulating the target genes of miRNAs. In this study, a lncRNA, lncRNA08489 was identified to be the ceRNA of miR482e-3p in tomato plants. The expression patterns of lncRNA08489 and miR482e-3p showed opposite trends after tomato plants infected with Phytophthora infestans. In tomato leaves overexpressing lncRNA08489 (OE08489), the expression level of miR482e-3p decreased and its target gene, NBS-LRR increased. After infection with P. infestans , the resistance of OE08489 plants was stronger than that of the wild type, and the reactive oxygen species (ROS) scavenging ability of OE08489 plants was significantly improved. Taken together, these results indicated that lncRNA08489 acted as a ceRNA to decoy miR482e-3p and regulate the expression of NBS-LRR to enhance tomato resistance through ROS-scavenging system. • LncRNA08489 modulated the accumulation of NBS-LRR through decoying miR482e-3p. • LncRNA08489 acted as a positive regulator of tomato resistance to Phytophthora infestans infection. • Overexpressing lncRNA08489 tomato increased the ROS-scavenging. [ABSTRACT FROM AUTHOR]

The ascomycete Cordyceps genus has been used as valued traditional Chinese medicine and functional food. Solid-state fermentation (SSF) of soybean, chickpea, black bean, and mung bean with Cordyceps militaris was performed for 35 days at 22°C, and then the biomass, total phenolic content (TPC), and total flavonoid content (TFC) increased significantly with the extension of fermentation time. The cordycepin content in four SSF-beans was as high as 8.33, 11.12, 10.43, and 6.64 mg/g, respectively. Moreover, the fermentation improved the 1,1′-diphenyl-2- picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonate) (ABTs) radical scavenging capacity, ferric reducing antioxidant power (FRAP) and ACE inhibition ability. Overall, the findings of the study stated clearly that SSF of beans with C. militaris was a potentially promising way to enhance the nutritional, physico-chemical, and biological properties of the substrate. Cordyceps-fermented products may serve as a novel valuable nutritional and functional food in health industry. [ABSTRACT FROM AUTHOR]

Background: Distant metastasis to vital organs is the major contributor to breast cancer mortality, and regional lymph node metastasis is an important facilitator of distant metastasis and recurrence in this cancer. The early diagnosis and precise treatment of lymph node metastasis are crucial for staging and prognosis in breast cancer. Herein, we report a visualized precision medicine nanoplatform of metastatic lymph nodes for ultrasonic/photoacoustic (US/PA) dual modal imaging-guided in situ targeted hyperthermia-combined chemotherapy. Results: Carbon nanoparticles (CNs), approved by the China Food and Drug Administration, were loaded with docetaxel and rationally combined with anti-hypoxia-inducible factor 1α antibody-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles to achieve the combination of passive targeting at the lymph nodes and intracellular targeting at HIF 1α factor. The accumulation and retention of nanoparticles in metastatic lymph nodes via lymphatic delivery were enhanced. Docetaxel could be effectively offloaded by CNs that have active carbon nanoparticles, and the PLGA membrane prevented drug leakage. The nanoparticles exhibited excellent photothermal performance with a photothermal conversion efficiency of 28.9%, killing tumor cells in metastatic lymph nodes through hyperthermia. In vitro and in vivo systematic evaluations revealed that hyperpyrexia triggered the rupture of nanoparticles caused by the phase transition of perfluorohexane, resulting in docetaxel release for achieving in situ hyperthermia-combined chemotherapy. Conclusions: The laser-triggered highly efficient in situ chemotherapy nanosystem achieves targeted synergistic chemo-hyperthermia treatment of metastatic lymph nodes, and lymphatic delivery represents a strategy to avoid additional injury caused by drugs entering the blood circulation. [ABSTRACT FROM AUTHOR]

All living organisms need energy to carry out their essential functions. The importance of energy metabolism is increasingly recognized in human pluripotent stem cells. Energy production is not only essential for cell survival and proliferation, but also critical for pluripotency and cell fate determination. Thus, energy metabolism is an important target in cellular regulation and stem cell applications. In this review, we will discuss key factors that influence energy metabolism and their association with stem cell functions. [ABSTRACT FROM AUTHOR]