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Grid-stiffened structures are widely used in industrial equipment, where the layout of stiffener unit cells is critical in the structural performance. However, owing to the lack of design techniques, existing stiffener unit cell designs are often achieved only by comparative selection among several common cell configurations. In this study, a deep learning-based intelligent optimization framework for the stiffener unit cell of grid-stiffened panels was proposed. First, a database containing nearly 10,000 stiffener unit cells was generated by traversal while considering the manufacturability. Feature extraction was then performed on the generated database using a variational autoencoder and mapped to a 16-dimensional continuous latent design space according to geometric features. Subsequently, in this latent space, a Gaussian process model was established, and the maximum expected improvement criterion was utilized to drive the model update and optimization search, thus realizing data-driven optimization for the stiffener unit cell of grid-stiffened panels. In three typical numerical examples, compared with the best of the traditional stiffener unit cells, the obtained optimal designs were improved by 25.61%, 25.88%, and 10.66%, respectively, demonstrating the effectiveness of this method as an alternative stiffener unit cell design method. Furthermore, this study also indicates the significant potential of geometric feature extraction and further structural layout optimization via deep learning. [ABSTRACT FROM AUTHOR]

The characteristics of dissolved organic matter (DOM) in road runoff under different traffic densities were compared using resin fractionation, molecular weight distribution analysis, three-dimensional excitation-emission matrix fluorescence spectroscopy, and UV–visible spectroscopy. Heavy traffic density strongly increased the concentration of DOM in road runoff, resulting in higher dissolved organic carbon. The distribution of molecular weights in DOM was not influenced by the traffic. DOM was dominated by colloidal organic matter with molecular weight in the 1 kDa to 0.45 μm size range. Hydrophobic fractions accounted for a large proportion than hydrophilic fractions in DOM, and hydrophobic acids increased with higher traffic density. Traffic density did not alter the fluorescent substances in DOM, including fulvic-like UV fluorescent substances and protein-like substances. However, more tryptophan-like protein substances were found in DOM from road runoff with heavy traffic. Moreover, the aromatization degree of DOM was not affected by heavy traffic, while the degree of humification decreased. [ABSTRACT FROM AUTHOR]

This work presented a novel strategy to integrate colorant and stabilizing effects of BSA-crocin I (BC) nanoparticles with gel-like structure of high internal phase Pickering emulsion (HIPPE, φ = 0.75). The BSA was cross-lined with crocin I to obtain BC nanoparticles for stabilizing HIPPE. When pH = 7.4, the particle size of BC nanoparticles was 326.65–366.40 nm with low polydispersity index (PDI) around 0.5 and zeta potential around −8 mV. The three-phase contact angle of BC nanoparticles was approaching 90°, indicating the strong absorptive capacity at the O/W interface. CLSM images showed the BC nanoparticles surrounded the oil droplets in the emulsions. Specifically, BC-1.5 (7.5% BSA and 0.1125% crocin I)-stabilized HIPPE exhibited the highest stability, with a Turbiscan stability index (TSI) value of 1.3. The thixotropic recovery degree of BC-1.5-stabilized HIPPE was the highest, while the G0′ and G0″ were the lowest, which confirmed that BC-1.5 constructed the most compact gel-network structure around emulsion droplets. The color difference of BC-1.5-stabilized HIPPE was much lower than 1 throughout the UV treatment with the lowest oxidation rate of gardenia oil. The colorimetric and oxidative results verified the color-protective and anti-oxidative abilities of BC nanoparticle-stabilized HIPPE, which might be used for the improvement of the meat product. [ABSTRACT FROM AUTHOR]

[Display omitted] • Inhibition of TDP-43 exerts neuroprotective effects in vivo. • TDP-43 knockdown inactivates the cGAS pathway. • TDP-43 is found to be accumulated in microglia with H/R treatment. Microglia are damaged during cerebral ischemia–reperfusion (I/R). This study was performed to investigate the regulatory effect of tAR DNA-binding protein-43 (TDP-43) on microglia after cerebral I/R in vitro and in vivo. The hypoxia/reoxygenation (H/R) treated microglia and rats with middle cerebral artery occlusion surgery were constructed respectively. The TDP-43 expression in brain tissues and microglia of each group was evaluated by qPCR and western blotting methods. Cell viability and cell apoptosis were combined to evaluate the degree of cell injury. As for animal experiments, neurological score and infarct volume were obtained to evaluate neurological injury. The levels of TDP-43 in the brain tissues of I/R group were higher than that in sham group. Both TDP-43 and Iba1, a typical microglia marker, were expressed in the brain tissues. TDP-43 was also elevated in microglia with H/R treatment. Inhibition of TDP-43 significantly down-regulated neurological deficit scores of rats after I/R surgery, and weakened the H/R treatment induced injury by promoting cell viability, inhibiting cell apoptosis, down-regulating IL-6 and iNOS levels, and up-regulating Arg-1 and IL-10 levels. Inactivation of cGAS pathway mediated by TDP-43 knockdown protects microglia from H/R treatment induced injury. The highly expressed TDP-43 level is associated with cerebral I/R, and inhibition of TDP-43 protects microglia from H/R induced injury through cGAS pathway in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Phosphoenolpyruvate (PEP) is an essential intermediate metabolite that is involved in various vital biochemical reactions. However, achieving the direct and accurate quantification of PEP in plasma or serum poses a significant challenge owing to its strong polarity and metal affinity. In this study, a sensitive method for the direct determination of PEP in plasma and serum based on ethylenediaminetetraacetic acid (EDTA)-facilitated hydrophilic interaction liquid chromatography–tandem mass spectrometry was developed. Superior chromatographic retention and peak shapes were achieved using a zwitterionic stationary-phase HILIC column with a metal-inert inner surface. Efficient dechelation of PEP–metal complexes in serum/plasma samples was achieved through the introduction of EDTA, resulting in a significant enhancement of the PEP signal. A PEP isotopically labelled standard was employed as a surrogate analyte for the determination of endogenous PEP, and validation assessments proved the sensitivity, selectivity, and reproducibility of this method. The method was applied to the comparative quantification of PEP in plasma and serum samples from mice and rats, as well as in HepG2 cells, HEK293T cells, and erythrocytes; the results confirmed its applicability in PEP-related biomedical research. The developed method can quantify PEP in diverse biological matrices, providing a feasible opportunity to investigate the role of PEP in relevant biomedical research. [Display omitted] • A novel, facile and accurate method for the direct determination of PEP in complex biological matrices is developed. • EDTA is an indispensable additive to plasma/serum to dechelate PEP-metal adducts and release free PEP molecules. • The developed method provides a feasible way for delving deeper the significance of PEP in relevant biomedical research. [ABSTRACT FROM AUTHOR]

The nucleus accumbens (NAc) is critical in mediating reward seeking and is also involved in negative emotion processing, but the cellular and circuitry mechanisms underlying such opposing behaviors remain elusive. Here, using the recently developed AAV1-mediated anterograde transsynaptic tagging technique in mice, we show that NAc neurons receiving basolateral amygdala inputs (NAcBLA) promote positive reinforcement via disinhibiting dopamine neurons in the ventral tegmental area (VTA). In contrast, NAc neurons receiving paraventricular thalamic inputs (NAcPVT) innervate GABAergic neurons in the lateral hypothalamus (LH) and mediate aversion. Silencing the synaptic output of NAcBLA neurons impairs reward seeking behavior, while silencing of NAcPVT or NAcPVT→LH pathway abolishes aversive symptoms of opiate withdrawal. Our results elucidate the afferent-specific circuit architecture of the NAc in controlling reward and aversion. The nucleus accumbens (NAc) is involved in mediating reward seeking and negative valence. Here, the authors present evidence for afferent-specific circuitry of the NAc in the control of reward and aversion via two distinct pathway. [ABSTRACT FROM AUTHOR]

Clear cell carcinoma (CCC) of the cervix (cCCC) is a rare and aggressive type of human papillomavirus (HPV)‐negative cervical cancer with limited effective treatment options for recurrent or metastatic disease. Historically, CCCs of the lower genital tract were associated with in utero diethylstilbestrol exposure; however, the genetic landscape of sporadic cCCCs remains unknown. Here we sought to define the molecular underpinning of cCCCs. Using a combination of whole‐exome, targeted capture, and RNA‐sequencing, we identified pathogenic genetic alterations in the Hippo signaling pathway in 50% (10/20) of cCCCs, including recurrent WWTR1 S89W somatic mutations in 40% (4/10) of the cases harboring mutations in the Hippo pathway. Irrespective of the presence or absence of Hippo pathway genetic alterations, however, all primary cCCCs analyzed in this study (n = 20) harbored features of Hippo pathway deregulation at the transcriptomic and protein levels. In vitro functional analysis revealed that expression of the WWTR1 S89W mutation leads to reduced binding of TAZ to 14‐3‐3, promoting constitutive nuclear translocation of TAZ and Hippo pathway repression. WWTR1 S89W expression was found to lead to acquisition of oncogenic behavior, including increased proliferation, migration, and colony formation in vitro as well as increased tumorigenesis in vivo, which could be reversed by targeted inhibition of the TAZ/YAP1 complex with verteporfin. Finally, xenografts expressing WWTR1 S89W displayed a shift in tumor phenotype, becoming more infiltrative as well as less differentiated, and were found to be composed of cells with conspicuous cytoplasmic clearing as compared to controls. Our results demonstrate that Hippo pathway alterations are likely drivers of cCCCs and likely contribute to the clear cell phenotype. Therapies targeting this pathway may constitute a new class of treatment for these rare, aggressive tumors. © 2022 The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]