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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]

Aims/Introduction Materials and Methods Results Conclusions We investigated the relationship of circulating TSP‐1 mRNA and miR‐194 with diabetic kidney disease’s degree.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.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.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]

This document is a correction notice for an article titled "Circ-ZEB1 promotes PIK3CA expression by silencing miR-199a-3p and affects the proliferation and apoptosis of hepatocellular carcinoma" published in the journal Molecular Cancer. The correction addresses two errors in the figures of the original article, specifically a typo in the subscript of the X-axis in Fig. 1B and an incorrect image in Fig. 3C. The authors provide the correct figures and state that these errors do not affect the overall results and conclusions of the study. The corrected figures show the expression of circ-ZEB1 and PIK3CA in hepatocellular carcinoma tissues and cells, as well as the effects of circ-ZEB1 downregulation on cell proliferation. The correction notice is authored by Weiwei Liu, Lu zheng, Rongguiyi Zhang, Ping Hou, Jiakun Wang, Linquan Wu, and Jing Li. [Extracted from the article]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

To achieve greener healthcare with the goal of net-zero carbon, it is urgent to motivate healthcare-employees to voluntarily participate in green behavior. Our focus is on examining a novel predictor of voluntary green behavior (VGB): socially responsible human resource management (SRHRM). Drawing on social information processing theory, a theoretical model was built to linking SRHRM and VGB. Based on the healthcare sector, we examined the mediating effect of green passion and the moderating effect of CSR attributions in the above mediation. We employed two studies: Study 1, which includes two experiments to examine the boundary of CSR attributions (H1 and H4), and Study 2, which empirically tested the mediated moderation model (H1–H4). We found that (a) SRHRM was positively associated with VGB; (b) green passion mediates the relation between SRHRM and VGB; and (c) CSR attributions moderate the association between SRHRM and green passion and influence the indirect effect of SRHRM on VGB (via green passion). We further elaborate on the implications, acknowledge limitations, and propose directions for future research. [ABSTRACT FROM AUTHOR]

To better understand the ecological effects of mariculture, the diversity distribution, determinant and interaction of microeukaryote communities from fish cage and suspended shellfish farming were investigated in three bays of South China Coast. Our alpha and beta diversity analyses showed that the difference of the microeukaryote community between fish and shellfish farming was more significant at local than regional scale, and microeukaryotes respond more to spatial effect than mariculture effect at regional scale. Mantel test, variation partitioning analysis and co-occurrence network analysis revealed that the environmental factors especially chemical and biotic factors contributed more to community assembly in fish than shellfish farming. Based on the comparisons of community composition and determinant between fish and shellfish farming, the effect mechanisms of the two farming types on microeukaryote community were proposed. Fish farming brings significant environmental variation and thus has strong bottom-up impacts on microeukaryotes, while shellfish farming exerts a grazing pressure on microeukaryotes by filter-feeding and has top-down control to them. Furthermore, the network stability analyses revealed weaker community stability in fish than shellfish farming, suggesting that the microeukaryote community was more sensitive to environmental change deduced by fish than shellfish farming. Overall, this study revealed the different influencing mechanisms of fish and shellfish mariculture on microeukaryotes, which will improve the understanding of the ecological effects of mariculture and provide guidance for the management of mariculture under future environmental pressures. [Display omitted] • Effects of mariculture on microeukaryotic community was more significant at local than regional scale. • Chemical and biotic factors contributed more to community assembly in fish than shellfish farming. • Fish farming had strong bottom-up impacts on microeukaryotic community; Shellfish farming exerted top-down control to them. • Microeukaryote community was more sensitive to environmental change deduced by fish than shellfish farming. • Management practices and ecological remediation should be carried out in principle of adaptation to mariculture types. [ABSTRACT FROM AUTHOR]

[Display omitted] • Temple skin temperature reflects an increased level of thermal stress in high temperatures. • The cognitive performance significantly changed with the increase in temple skin temperature. • An inverted U-shaped curve demonstrates the relationship between the accuracy of cognitive performance and temple skin temperature. • Introducing the temple skin temperature-cognitive performance(TST-CP) model to predict cognitive performance based on temple skin temperature. • The TST-CP model has demonstrated strong reliability in predicting cognitive performance. The study aimed to explore temple skin temperature as a potential physiological indicator reflecting the impact of high temperatures on cognitive performance. The feasibility of this indicator was substantiated through a thorough analysis of climate-controlled experimental data conducted at varying high temperatures: 33 °C, 37 °C, and 39 °C. The temple skin temperature was carefully monitored during the experiments, alongside cognitive tests that measured work memory, concentration, and neurobehavioral abilities. In total, 1459 valid samples were collected, contributing to the robustness of the study. The results elucidated a noteworthy finding: a significant decline in cognitive test accuracy commenced when the temple skin temperature reached 37 °C (p < 0.05). Intriguingly, the correlation between the relative accuracy of cognitive tests and temple skin temperature showcased a distinctive inverted U-shaped pattern. Employing a quadratic regression model facilitated the quantification of this relationship, yielding coefficients of determination (R2) for the fitted models that were close to or exceeded 0.9. These findings imply that temple skin temperature can be used to assess the effect of high temperature on cognitive performance. Furthermore, this research suggests the promising prospect of employing temple skin temperature for real-time monitoring of job safety in high-temperature environments. [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]

A high-speed-level gear transmission system model of a wind turbine is presented considering a time-varying wind load and an electromagnetic torque disturbance, along with eccentricity, dynamic backlash, and friction force. The auto-regressive model is employed for simulating the time-varying wind load in the realistic wind field as external excitation. A doubly fed induction generator model of the wind turbine is established to calculate the disturbance quantity of electromagnetic torque. The nonlinear differential equations of the system are strictly deduced using Lagrange equation and solved by the fourth-order Runge-Kutta method. The effect of friction on the dynamic response of the high-speed-level gear transmission system is analyzed with the time-varying wind load and the electromagnetic torque disturbance. These results show that the friction force is critical because frequency amplitude and components can be changed by it. The friction force also enlarges vibration displacement. The low-frequency components in the vertical direction are affected gravely by the friction force without electrical disturbance. In addition, sidebands exist in the vicinity of the low-frequency parts as the electromagnetic torque disturbance appears at the output end. The amplitude of the low-frequency component is further increased because of electromagnetic torque disturbance. This shows the frequency characteristics of the slight gear system fault. The study offers some fresh references into the design and diagnosis of the gear system. [ABSTRACT FROM AUTHOR]

Due to the specificity of the geological background, terrestrial strata are widely distributed in the major hydrocarbon-bearing basins in China. In addition, terrestrial shales are generally featured with high thickness, multiple layers, high TOC content, ideal organic matter types, and moderate thermal evolution, laying a solid material foundation for hydrocarbon generation. However, the quantitative characterization study on their pore structure remains inadequate. In this study, core samples were selected from the Middle Jurassic Lianggaoshan Formation in the southeastern Sichuan Basin of the Upper Yangtze Region for analyses on its TOC content and mineral composition. Besides, experiments including oil washing, the adsorption/desorption of CO2 and nitrogen, and high-pressure mercury pressure experiments were carried out. The pore structure of different petrographic types of terrestrial shales can be accurately and quantitatively characterized with these works. The following conclusions were drawn: for organic-rich mixed shales and organic-rich clay shales, the TOC content is the highest; the pore volume, which is primarily provided by macropores and specific surface area, which is provided by mesopores, was the largest, thus providing more space for shale oil and gas reservation. The pores take on a shape either close to a parallel plate slit or close to or of an ink bottle. For organic-matter-bearing shales, both the pore volume and specific surface area are the second-largest and are provided by the same sized pores with organic-rich mixed shales. Its pores take on a shape approximating either a parallel plate slit or an ink bottle. Organic-matter-bearing mixed shales have the lowest pore volume and specific surface area; its pore volume is primarily provided by macropores, and the specific surface area by mesopores and the shape of the pores are close to an ink bottle. [ABSTRACT FROM AUTHOR]

This article presents a simple and intuitive solution for multilabel image classification, which achieves the competitive performance on the popular COCO and PASCAL VOC benchmarks. The main idea is to capture how humans perform this task: we recognize both labels (i.e., objects and attributes) and the correlation of labels at the same time. Here, label recognition is performed by a standard ConvNet pipeline, whereas label correlation modeling is done by projecting both labels and image features extracted by the ConvNet to a common latent vector space. Specifically, we carefully design the loss function to ensure that: 1) labels and features that co-appear frequently are close to each other in the latent space and 2) conversely, labels/features that do not appear together are far apart. This information is then combined with the original ConvNet outputs to form the final prediction. The whole model is trained end-to-end, with no additional supervised information other than the image-level supervised information. Experiments show that the proposed method consistently outperforms previous approaches on COCO and PASCAL VOC in terms of mAP, macro/micro precision, recall, and $F$ -measure. Further, our model is highly efficient at test time, with only a small number of additional weights compared to the base model for direct label recognition. [ABSTRACT FROM AUTHOR]

The large deformation issue in soft rock mass is a worldwide difficulty that has puzzled tunnel engineering for a century and a half. Previous studies have mainly focused on a large deformation mechanism, prediction, and control of soft rock with single lithology, while there are limited studies on the tunneling-induced large deformation in monoclinic and soft-hard interbedded rock strata. This paper studies the deformation law, evolution process, and failure mechanism of a tunnel excavated in monoclinic and soft-hard interbedded rock mass by onsite measurements in the No. 3 inclined shaft of the Muzhailing Tunnel, which is a key control project of the Lanzhou-Haikou National Expressway. The achieved results indicated that the tunnel deformation was characterized by significant asymmetry, the maximum deformation in the cross section was observed to occur in the normal direction of the bedding plane, and the side of the larger deformation was consistent with the dip direction of the strata. The vertical displacements were greater than the horizontal displacements except for the right foot of the middle bench, and the primary lining at the upper left of the tunnel had intruded into the space of the secondary lining and had to be demolished and reconstructed. The displacement speed and amount mostly reached the peak in the construction stage of the middle bench, and its displacement amount accounted for about half of the total displacement. The spatiotemporal curves of large deformation could be divided into four stages according to the excavation time and the distance from the tunnel face. Two types of exponential functions were used to fit and predict the tunnel displacement, which displayed good applicability. The disaster evolution process of large deformations was summarized into five stages on a macro scale: premise, gestation, development (including four substages), occurrence, and treatment of large deformation. The failure mechanism of monoclinic and soft-hard interbedded rock mass is mainly the bending-tensile failure of thin-layered strata. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to analyze the impact of different biopsy protocols on the rate of mosaic blastocysts. Methods: This is a retrospective cohort study which included 115 cycles with pre-implantation genetic testing for aneuploidy (PGT-A). Two groups were allocated based on the biopsy protocols: method 1 group, the zona pellucida (ZP) was drilled on day 3 embryos followed by trophectoderm (TE) biopsy; and method 2 group, the ZP was opened on day 5 or 6 blastocysts followed by TE biopsy. All biopsy samples were assessed using next-generation sequencing (NGS) at a single reference laboratory. The euploid, aneuploid, and mosaic blastocyst rates and clinical outcomes were compared. Results: The mosaicism rate in the method 1 group was 19.58%, significantly higher than the method 2 group (8.12%; P < 0.05). No statistically significant difference was observed in euploid, aneuploid blastocyst rates, and clinical pregnancy rates between the two groups. Logistic regression analysis indicated that the biopsy protocols were independently associated with the mosaicism rates among all the variables. Conclusions: The present study showed that different biopsy protocols may have an impact on the mosaic blastocyst rate. ZP opening on day 3 combined with TE biopsy might increase the incidence of mosaic blastocysts. [ABSTRACT FROM AUTHOR]

Improvement of the mechanical properties of advanced ceramics fabricated by additive manufacturing has been a prerequisite for their wide applications. In this work, zirconia-toughened alumina (ZTA) parts with a variety of yttria-stabilized zirconia (YSZ) content were fabricated by stereolithography (SL) technology, based on the appropriate self-holding ability of the viscoelastic paste and application of conformal contactless support strategy. Combining microstructural analysis and mechanical assessment by three-point bending and indentation tests, the influence of YSZ content on the SL process and subsequent mechanical properties was discussed. The results showed that the optimized matching of flexural strength (477.54 MPa) and fracture toughness (6.56 MPa m1/2) was acquired by ZTA ceramic with a YSZ content of 20 wt%. When the YSZ content reached 30 wt%, agglomerations formed and led to a negative influence on the properties of ZTA ceramics. It is confirmed that the combined contribution from the addition of YSZ on the improvement of mechanical property and influence of the SL process should be synthetically considered during the design of ceramic paste feedstock for such additive manufacturing. [ABSTRACT FROM AUTHOR]

Functional gradient materials (FGMs) are composite materials made up of two or more materials, with components or structures that gradually change, resulting in a gradual change in performance and functionality. Additive manufacturing (AM) technologies have the potential to greatly benefit the development of FGMs by enabling efficient production of complex-shaped parts. The preparation and characterization of gradient alloys produced by AM, including metal-metal, metal-ceramic, ceramic-ceramic, and metal-organic, are discussed in this paper. An overview of the solutions and countermeasures for challenges encountered during FGM preparation is presented in this paper. These challenges include the generation of intermetallic compounds, the mismatching of thermophysical parameters, and the variation of the dilution rate across different gradient layers. Finally, potential areas for future research are outlined based on a summary of existing research. This work provides vital guidelines for future fabrication of FGMs. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Although prior studies showed a correlation between environmental manganese (Mn) exposure and neurodevelopmental disorders in children, the results have been inconclusive. There has yet been no consistent biomarker of environmental Mn exposure. Here, we summarized studies that investigated associations between manganese in biomarkers and childhood neurodevelopment and suggest a reliable biomarker.Methods: We searched PubMed and Web of Science for potentially relevant articles published until December 31th 2019 in English. We also conducted a meta-analysis to quantify the effects of manganese exposure on Intelligence Quotient (IQ) and the correlations of manganese in different indicators.Results: Of 1754 citations identified, 55 studies with 13,388 subjects were included. Evidence from cohort studies found that higher manganese exposure had a negative effect on neurodevelopment, mostly influencing cognitive and motor skills in children under 6 years of age, as indicated by various metrics. Results from cross-sectional studies revealed that elevated Mn in hair (H-Mn) and drinking water (W-Mn), but not blood (B-Mn) or teeth (T-Mn), were associated with poorer cognitive and behavioral performance in children aged 6-18 years old. Of these cross-sectional studies, most papers reported that the mean of H-Mn was more than 0.55 μg/g. The meta-analysis concerning H-Mn suggested that a 10-fold increase in hair manganese was associated with a decrease of 2.51 points (95% confidence interval (CI), - 4.58, - 0.45) in Full Scale IQ, while the meta-analysis of B-Mn and W-Mn generated no such significant effects. The pooled correlation analysis revealed that H-Mn showed a more consistent correlation with W-Mn than B-Mn. Results regarding sex differences of manganese associations were inconsistent, although the preliminary meta-analysis found that higher W-Mn was associated with better Performance IQ only in boys, at a relatively low water manganese concentrations (most below 50 μg/L).Conclusions: Higher manganese exposure is adversely associated with childhood neurodevelopment. Hair is the most reliable indicator of manganese exposure for children at 6-18 years of age. Analysis of the publications demonstrated sex differences in neurodevelopment upon manganese exposure, although a clear pattern has not yet been elucidated for this facet of our study. [ABSTRACT FROM AUTHOR]

We consider the existence of solutions for the following Hadamard-type fractional differential equations: { D α H u (t) + q (t) f (t , u (t) , H D β 1 u (t) , H D β 2 u (t)) = 0 , 1 < t < + ∞ , u (1) = 0 , D α − 2 H u (1) = ∫ 1 + ∞ g 1 (s) u (s) d s s , D α − 1 H u (+ ∞) = ∫ 1 + ∞ g 2 (s) u (s) d s s , where 2 < α ≤ 3 , 0 < β 1 ≤ α − 2 < β 2 ≤ α − 1 , f : J × R 3 → R satisfies the q-Carathéodory condition, q , g 1 , g 2 : J → R + are nonnegative, where J = [ 1 , + ∞) . Nonlinear term f is dependent on the fractional derivative of lower order β 1 , β 2 , which creates additional complexity to verify the existence of solutions. The singularity occurring in our problem is associated with D β 2 H u ∈ C (1 , + ∞) at the left endpoint t = 1 (if β 2 < α − 1 ). [ABSTRACT FROM AUTHOR]

Ground pressure is a significant parameter for the mobility, tractive performance, and soil compaction. In this study, an analytical model for predicting ground pressure distribution under a rigid-flexible tracked vehicle on soft ground was developed. The model considered the primary design parameters of the tracked vehicle, soil characteristics, and soil shear. The ground pressure was not uniform, and its maximum values under the roadwheels were 90.20, 103.57, and 150.14 kPa. The ground pressure was inversely proportional to the ratio of the lengths of the flexible track and rigid grouser. An experiment was conducted to verify the analytical model. The maximum error between the measured and simulated results was smaller than 8%, thereby verifying the analytical model. [ABSTRACT FROM AUTHOR]

Lung cancer, especially non-small cell lung cancer (NSCLC), is the most common malignant tumor associated with poor prognosis. Angiogenesis plays a vital role in NSCLC, and could be used in tumor staging and therapy evaluation. CD93 (C1q receptor) is reportedly a key regulator of tumor angiogenesis. In the present study, the efficacy and specificity of a 125I-labeled CD93-specific monoclonal antibody (125I-anti-CD93 mAb) in detecting NSCLC xenografts were analyzed, and the association between CD93 expression and 125I-anti-CD93 mAb uptake by tumors was evaluated. The targeting ability of 125I-anti-CD93 mAb enabled its rapid, continuous and highly specific accumulation in CD93-expressing tumors in vivo. These results revealed the potential applicability of 125I-anti-CD93 mAb for non-invasive imaging diagnosis of CD93-positive NSCLC. [ABSTRACT FROM AUTHOR]

Given two video frames $X_{0}$ and $X_{n+1}$ , we aim to generate a series of intermediate frames $Y_{1}, Y_{2}, \ldots, Y_{n}$ , such that the resulting video consisting of frames $X_{0}, Y_{1}-Y_{n}, and X_{n+1}$ appears realistic to a human watcher. Such video generation has numerous important applications, including video compression, movie production, slow-motion filming, video surveillance, and forensic analysis. Yet, video generation is highly challenging due to the vast search space of possible frames. Previous methods, mostly based on video prediction and/or video interpolation, tend to generate poor-quality videos with severe motion blur. This paper proposes a novel, end-to-end approach to video generation using generative adversarial networks (GANs). In particular, our design involves two concatenated GANs, one capturing motions and the other generating frame details. The loss function is also carefully engineered to include adversarial loss, gradient difference (for motion learning), and normalized product correlation loss (for frame details). Experiments using three video datasets, namely, Google Robotic Push, KTH human actions, and UCF101, demonstrate that the proposed solution generates high-quality, realistic, and sharp videos, whereas all previous solutions output noisy and blurry results. [ABSTRACT FROM AUTHOR]

Coal is a non-renewable fossil energy source on which humanity relies heavily, and producing one ton of raw coal requires the discharge of 2–7 tons of mine water from the ground. The huge drainage task increases the cost of coal mining in coal mines significantly, so saving the drainage cost while guaranteeing the safe production of coal mines is a problem that needs to be solved urgently. Most of the fuzzy controllers used in the traditional dynamic planning methods applied to mine drainage are two-dimensional fuzzy controllers with limited control effect, so the traditional two-dimensional fuzzy controllers are improved by introducing the rate of change of gushing water to form a three-dimensional fuzzy controller with three-dimensional control of instantaneous section—water level—rate of change of gushing water, and at the same time, the optimized dynamic planning method is designed by combining the Avoiding Peak Filling Valley strategy and the optimal dy-namic planning method is used in conjunction with the un-optimized dynamic planning method. The optimized dynamic planning method is applied to the same coal mine water silo gushing water experiments; experimental comparison found that the pumping station system before the optimi-zation of the electricity consumed is 52,586 yuan/day, while after the optimization of the electricity consumed is reduced to 41,692 yuan/day, the cost per day consumed compared with the previous reduction of 20.69%, a year can be saved 3,969,730 yuan. Therefore, the mine water bin drainage method based on fuzzy control and Avoiding Peak Filling Valley strategy proposed in this paper can be used as an improvement method of the existing mine drainage method, which can further ex-pand the economic benefits of coal mines and realize safe production while realizing cost savings. [ABSTRACT FROM AUTHOR]

Background: The dysregulated mechanistic target of rapamycin complex 1 (mTORC1) signaling plays a critical role in ferroptosis resistance and tumorigenesis. However, the precise underlying mechanisms still need to be fully understood. Methods: Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α) expression in mTORC1-activated mouse embryonic fibroblasts, cancer cells, and laryngeal squamous cell carcinoma (LSCC) clinical samples was examined by quantitative real-time PCR (qRT–PCR), western blotting, immunofluorescence (IF), and immunohistochemistry. Extensive in vitro and in vivo experiments were carried out to determine the role of ERO1α and its downstream target, member 11 of the solute carrier family 7 (SLC7A11), in mTORC1-mediated cell proliferation, angiogenesis, ferroptosis resistance, and tumor growth. The regulatory mechanism of ERO1α on SLC7A11 was investigated via RNA-sequencing, a cytokine array, an enzyme-linked immunosorbent assay, qRT–PCR, western blotting, IF, a luciferase reporter assay, and a chromatin immunoprecipitation assay. The combined therapeutic effect of ERO1α inhibition and the ferroptosis inducer imidazole ketone erastin (IKE) on mTORC1-activated cells was evaluated using cell line-derived xenografts, LSCC organoids, and LSCC patient-derived xenograft models. Results: ERO1α is a functional downstream target of mTORC1. Elevated ERO1α induced ferroptosis resistance and exerted pro-oncogenic roles in mTORC1-activated cells via upregulation of SLC7A11. Mechanically, ERO1α stimulated the transcription of SLC7A11 by activating the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ERO1α inhibition combined with treatment using the ferroptosis inducer IKE exhibited synergistic antitumor effects on mTORC1-activated tumors. Conclusions: The ERO1α/IL-6/STAT3/SLC7A11 pathway is crucial for mTORC1-mediated ferroptosis resistance and tumor growth, and combining ERO1α inhibition with ferroptosis inducers is a novel and effective treatment for mTORC1-related tumors. [ABSTRACT FROM AUTHOR]

Lactate has emerged as a key player in regulating neural functions and cognitive processes. Beyond its function as an energy substrate and signal molecule, recent research has revealed lactate to serve as an epigenetic regulator in the brain. However, the molecular mechanisms by which lactate regulates spatial memory and its role in the prevention of cognitive disorders remain unclear. Herein, we injected L-lactate (10 μmol/kg/d for 6 d) into the mouse's hippocampus, followed by the Morris water maze (MWM) test and molecular analyses. Improved spatial memory performances were observed in mice injected with lactate. Besides, lactate upregulated the expression of synaptic proteins post-synaptic density 95 (PSD95), synaptophysin (SYP), and growth associated protein 43 (GAP43) in hippocampal tissues and HT22 cells, suggesting a potential role in synaptic transmission and memory formation. The facilitative role of monocarboxylate transporter 2 (MCT2), a neuron-specific lactate transporter, in this process was confirmed, as MCT2 antagonists attenuated the lactate-induced upregulation of synaptic proteins. Moreover, lactate induced protein lactylation, a post-translational modification, which could be suppressed by MCT2 inhibition. RNA sequencing of lactated-injected hippocampal tissues revealed a comprehensive gene expression profile influenced by lactate, with significant changes in genes associated with transcriptional progress. These data demonstrate that hippocampal lactate injection enhances spatial memory in mice, potentially through the upregulation of synaptic proteins and induction of protein lactylation, with MCT2 playing a crucial role in these processes. Our findings shed light on the multi-faceted role of lactate in neural function and memory regulation, opening new avenues for therapeutic interventions targeting cognitive disorders. [ABSTRACT FROM AUTHOR]

Alternative splicing (AS) plays a crucial role in regulating gene expression, function, and diversity. However, limited reports exist on the identification and comparison of AS in Eastern and Western pigs. Here, we analyzed 243 transcriptome data from eight tissues, integrating information on transcription factors (TFs), selection signals, splicing factors (SFs), and quantitative trait loci (QTL) to comprehensively study alternative splicing events (ASEs) in pigs. Five ASE types were identified, with Mutually Exclusive Exon (MXE) and Skipped Exon (SE) ASEs being the most prevalent. A significant portion of genes with ASEs (ASGs) showed conservation across all eight tissues (63.21–76.13% per tissue). Differentially alternative splicing genes (DASGs) and differentially expressed genes (DEGs) exhibited tissue specificity, with blood and adipose tissues having more DASGs. Functional enrichment analysis revealed coDASG_DEGs in adipose were enriched in pathways associated with adipose deposition and immune inflammation, while coDASG_DEGs in blood were enriched in pathways related to immune inflammation and metabolism. Adipose deposition in Eastern pigs might be linked to the down-regulation of immune-inflammation-related pathways and reduced insulin resistance. The TFs, selection signals, and SFs appeared to regulate ASEs. Notably, ARID4A (TF), NSRP1 (SF), ANKRD12, IFT74, KIAA2026, CCDC18, NEXN, PPIG, and ROCK1 genes in adipose tissue showed potential regulatory effects on adipose-deposition traits. NSRP1 could promote adipogenesis by regulating alternative splicing and expression of CCDC18. Conducting an in-depth investigation into AS, this study has successfully identified key marker genes essential for pig genetic breeding and the enhancement of meat quality, which will play important roles in promoting the diversity of pork quality and meeting market demand. [ABSTRACT FROM AUTHOR]

Alternative splicing (AS) is a crucial mechanism in post-transcriptional regulation, contributing significantly to the diversity of the transcriptome and proteome. In this study, we performed a comprehensive AS profile in nine tissues obtained from Duroc (lean-type) and Luchuan (obese-type) pigs. Notably, 94,990 AS events from 14,393 genes were identified. Among these AS events, it was observed that 80% belonged to the skipped exon (SE) type. Functional enrichment analysis showed that genes with more than ten AS events were closely associated with tissue-specific functions. Additionally, the analysis of overlap between differentially alternative splicing genes (DSGs) and differentially expressed genes (DEGs) revealed the highest number of overlapped genes in the heart and skeletal muscle. The novelty of our study is that it identified and validated three genes (PYGM, MAPK11 and CAMK2B) in the glucagon signaling pathway, and their alternative splicing differences were highly significant across two pig breeds. In conclusion, our study offers novel insights into the molecular regulation of diverse tissue physiologies and the phenotypic differences between obese- and lean-type pigs, which are helpful for pig breeding. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides and antibacterial nanostructures are two emerging classes of antimicrobial agents that differ from conventional small-molecule antibiotics. Combining these two types of antimicrobial agents into one entity may be an effective strategy to improve their antimicrobial efficiency. In this study, we demonstrated an effective antibacterial hybrid formed by covalently conjugating antibacterial gold nanoclusters (Au NCs, a novel antimicrobial nanostructure) and daptomycin (Dap, a cyclic lipopeptide antimicrobial peptide). The as-synthesized hybrid structure (Dap−Au NCs) not only inherits the intrinsic properties from both agents but also renders an enhanced synergistic effect. Compared with the physically mixed Au NCs and daptomycin (Dap+Au NCs), the Dap−Au NCs hybrid structure has a stronger bactericidal effect toward methicillin-resistant Staphylococcus aureus , a representative of multidrug-resistant bacteria. Dap−Au NCs could effectively disrupt bacterial membranes by creating more and/or larger holes in the membranes due to the localized daptomycin within the conjugated structure. These larger (and possibly more) holes motivate the entry of Dap−Au NCs into bacterial cells and lead to more serious damage of the bacteria at subcellular levels. Moreover, bacterial genomic DNA fragmentation was further quantified to show that Dap−Au NCs may induce severe DNA breaks. The strong DNA destruction benefited from localized high concentrations of reactive oxygen species (ROS) induced by the localization of Au NCs in the antimicrobial conjugation. The conjugated Au NCs could serve as a critical free radical generator to continuously produce ROS within the bacteria. The continuous ROS bombings also limit the capacity of the bacteria to develop drug resistance. In addition, a significant fluorescence enhancement of the hybrid structure was observed due to a novel aggregation-induced emission (AIE) pattern caused by the Au NCs and daptomycin conjugation. This conjugation strategy provides a new perspective for the synthesis of new antimicrobial agents as well as AIE-type fluorescence materials. [ABSTRACT FROM AUTHOR]

Abstract The determination of micromechanical properties of additive manufactured ceramics is essential to address reliability issues in engineering application. Alumina ceramics were fabricated by stereolithography-based additive manufacturing with different layer thickness. The microstructure and micro-mechanical properties were investigated systematically, by means of scanning electron microscopy, nanoindentation and micro-scratch tests. The characteristics of alumina ceramic green bodies mainly depended on the layer thickness, while scratch morphologies was discussed in terms of the integrity and homogeneity of microstructure. The results indicated that scratch damage evolution was independent of layer thickness since no correlation between cracking and layering characteristic was verified under all scratch tests. [ABSTRACT FROM AUTHOR]