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Objective: This study aimed to explore andrographolide’s mechanism of action and its protective effect on noise-induced hearing loss (NIHL). Materials and Methods: A mice animal model for NIHL was established through exposure to broadband noise at 120 dB sound pressure level for 4 h. Transcriptomics analysis and pharmacodynamic experiments were carried out. Results: Andrographolide enters the inner ear and effectively prevents hearing damage following noise exposure in the mice model for permanent hearing loss. Moreover, treatment with andrographolide inhibited the excessive activation of inflammatory factors in the cochleae of noise-exposed mice. Conclusion: Andrographolide might be a promising candidate for auditory protective drug investigation.

Many e-commerce platforms have established extensive networks of stations as their last-mile logistics infrastructure. This study investigates how this last-mile infrastructure may serve as an offline platform to connect customers and merchants in the physical world by leveraging walk-in traffic (organic interaction) and prompting interested customers through online intervention (induced interaction). Using free sample distribution as an example, we designed two large-scale studies in collaboration with Alibaba—an observational study across 1,032 stations and a randomized field experiment among 189,019 customers—to examine the causal effects of organic and induced interactions on customers' subsequent online purchases from the focal brands, respectively. We found that induced interaction drives significantly more online sales than organic interaction. Under induced interaction, the online intervention effectively increases the number of free samples distributed. Nevertheless, the more significant increase in online sales for induced claimers is not simply due to more free samples distributed but because the induced customers are more interested and more likely to purchase. We identified this phenomenon as a screening mechanism that facilitates an advantageous selection of customers claiming the samples. Customers willing to pay the additional travel cost to claim samples are more likely to purchase the focal brands afterward. Finally, we developed a customized targeting framework using a generalized random forest model to enhance the effectiveness of induced interaction at the last-mile stations. Our study raises a key insight that the "foot-in-the-door" traffic in an omnichannel environment can be fundamentally different depending on whether the offline customers are driven from the online channel. [ABSTRACT FROM AUTHOR]

Background: Hydrogel carrying exosomes shows better prospects for bone regeneration. Objective: This work investigated the effect of cross-linking N-succinyl chitosan-oxidated hyaluronic acid-based hydrogel loaded with bone marrow mesenchymal stem cell-derived exosomes on bone regeneration in cranial defects. Methods: Cross-linking N-succinyl chitosan-oxidated hyaluronic acid-based hydrogel loaded with bone marrow mesenchymal stem cell-derived exosomes was prepared, and utilized to treat bone marrow mesenchymal stem cells, human umbilical vein endothelial cells, and rats with cranial defects. Logical experiments were implemented to research the effect of the prepared hydrogel on osteogenesis and angiogenesis of cells in vitro, and on bone regeneration in rats with cranial defects. Results: Cross-linking N-succinyl chitosan-oxidated hyaluronic acid-based hydrogel loaded with bone marrow mesenchymal stem cell-derived exosomes showed good biocompatibility and self-healing property. It promoted osteogenic differentiation of bone marrow mesenchymal stem cells and angiogenesis of human umbilical vein endothelial cells, and facilitated osteogenic differentiation, angiogenesis and bone regeneration in rats with cranial defects. Conclusion: Cross-linking N-succinyl chitosan-oxidated hyaluronic acid-based hydrogel loaded with bone marrow mesenchymal stem cell-derived exosomes facilitated osteogenesis, angiogenesis and bone regeneration in rats with cranial defects. It might be an effective strategy for inducing bone regeneration in individuals with cranial defects.

Abstract Background Miller syndrome is a rare type of postaxial acrofacial dysostosis caused by biallelic mutations in the DHODH gene, which is characterized mainly by craniofacial malformations of micrognathia, orofacial clefts, cup‐shaped ears, and malar hypoplasia, combined with postaxial limb deformities like the absence of fifth digits. Methods In this study, a prenatal case with multiple orofacial‐limb abnormities was enrolled, and a thorough clinical and imaging examination was performed. Subsequently, genetic detection with karyotyping, chromosomal microarray analysis (CMA) and whole‐exome sequencing (WES) was carried out. In vitro splicing analysis was also conducted to clarify the impact of one novel variant. Results The affected fetus displayed typical manifestations of Miller syndrome, and WES identified a diagnostic compound heterozygous variation in DHODH, consisting of two variants: exon(1‐3)del and c.819 + 5G > A. We conducted a further in vitro validation with minigene system, and the result indicated that the c.819 + 5G > A variant would lead to an exon skipping in mRNA splicing. Conclusions These findings provided with the first exonic deletion and first splice site variant in DHODH, which expanded the mutation spectrum of Miller syndrome and offered reliable evidence for genetic counseling to the affected family.

Abstract Introduction Regulation of brain‐derived neurotrophic factor (BDNF) in the basal forebrain ameliorates sleep deprivation‐induced fear memory impairments in rodents. Antisense oligonucleotides (ASOs) targeting ATXN2 was a potential therapy for spinocerebellar ataxia, whose pathogenic mechanism associates with reduced BDNF expression. We tested the hypothesis that ASO7 targeting ATXN2 could affect BDNF levels in mouse basal forebrain and ameliorate sleep deprivation‐induced fear memory impairments. Methods Adult male C57BL/6 mice were used to evaluate the effects of ASO7 targeting ATXN2 microinjected into the bilateral basal forebrain (1 μg, 0.5 μL, each side) on spatial memory, fear memory and sleep deprivation‐induced fear memory impairments. Spatial memory and fear memory were detected by the Morris water maze and step‐down inhibitory avoidance test, respectively. Immunohistochemistry, RT‐PCR, and Western blot were used to evaluate the changes of levels of BDNF, ATXN2, and postsynaptic density 95 (PSD95) protein as well as ATXN2 mRNA. The morphological changes in neurons in the hippocampal CA1 region were detected by HE staining and Nissl staining. Results ASO7 targeting ATXN2 microinjected into the basal forebrain could suppress ATXN2 mRNA and protein expression for more than 1 month and enhance spatial memory but not fear memory in mice. BDNF mRNA and protein expression in basal forebrain and hippocampus was increased by ASO7. Moreover, PSD95 expression and synapse formation were increased in the hippocampus. Furthermore, ASO7 microinjected into the basal forebrain increased BDNF and PSD95 protein expression in the basal forebrain of sleep‐deprived mice and counteracted sleep deprivation‐induced fear memory impairments. Conclusion ASOs targeting ATXN2 may provide effective interventions for sleep deprivation‐induced cognitive impairments.

This investigation aims to analyze the effect of homogenization heat treatment at 1240 °C for 2 and 6 h on the hardness, distribution, morphology, and chemical composition of the δ-ferrite and sigma phases in 316L stainless steel cast billet. A field emission scanning electron microscope, combined with electron back-scattered diffraction, a field emission electron probe microanalyzer with a wavelength dispersive spectrometer, and a Vickers microhardness tester are applied to identify various phase evolutions in the cast billet. The morphology of the δ-ferrite and sigma phases in the austenite matrix of the 316L cast billet are strongly related to the subsequent hot and cold wire drawings. The homogenization heat treatment is expected to provide a driving force to form spheroid interdendritic δ-ferrite and to minimize the amount of the brittle sigma intermetallic compound in the austenite matrix. The homogenization heat treatment at 1240 °C effectively spheroidized all δ-ferrites into blunt ones in the cast billet. The transformation of δ-ferrite into sigma is dominated by temperature and cooling rate. The fast air cooling after homogenization between 1240 and 850 °C retards the precipitation of the sigma in the δ-ferrite. There are two δ-ferrite transformation mechanisms in this experiment. The direct transformation of the δ-ferrite into sigma is observed in the as-cast 316L stainless steel billet. In contrast, the eutectoid transformation of the δ-ferrite into the sigma and austenite dominates the 316L cast billet homogenized at 1240 °C, with a slow furnace cooling rate.

This study was meticulously conducted, delving into the epitaxial growth of nanothin β-In2Se3 films on sapphire (0001) using molecular beam epitaxy. The growth temperature was carefully set at 480 °C, and the selenium to indium flux ratio (RSe/In) was systematically varied from 1 to 100. The phase transformation from γ-In2Se3 to β-In2Se3 was precisely controlled by manipulating the RSe/In and confirmed through Raman scattering measurements and synchrotron-based grazing-incidence wide-angle X-ray scattering. The surface morphology for various RSe/In of In2Se3 was analyzed by atomic force microscopy (AFM). The lowest surface roughness is around 0.58 nm, which is achieved under the RSe/In = 60 growth condition. The nanothin β-In2Se3 film with a layer-by-layer atomic arrangement was verified by high-resolution transmission electron microscopy. According to the experimental results, the growth dynamics of In2Se3 are proposed to be step-flow growth and horizontal growth under RSe/In 45 and 60 conditions, respectively. This research underscores the control of the growth mechanism by Se/In flux and its role in facilitating the In2Se3 epitaxy for integration in the development of 2D-materials-based future electronic devices. [ABSTRACT FROM AUTHOR]

AlCoCrFeNi2.1+xwt.%TiC (x=3, 6, 9) coatings were prepared on H13 steel by laser cladding (LC) technology. It was characterized by a friction and wear test machine, optical microscope (OM), X-ray diffractometer (XRD), hardness tester, etc. The effects of different TiC contents on the microstructure and properties of AlCoCrFeNi2.1 coatings were analyzed. The results show that the coating microstructure without TiC addition is dominated by coarse columnar crystals and dendrites. After the addition of TiC, the coated massive crystals and equiaxed crystals become finer. XRD analysis reveals that the phase structure of the coating has FCC, B2 solid solution phase and TiC-reinforced phase. TiC phase can significantly improve the hardness of the coating. The microstructure reveals that fine TiC particles are widely distributed among the dendrites of the FCC matrix. The hardness and friction wear experiments revealed that the average hardness of the coatings with TiC has increased significantly compared to that of the substrate. The hardness of the AlCoCrFeNi2.1 with 9%TiC coating increased by 184.6% compared to that of the substrate. The friction coefficient was the smallest at 0.748. The lowest self-corrosion current was 9.040×10−7A⋅cm−2. The AlCoCrFeNi2.1 with 9%TiC coating had the best corrosion resistance. [ABSTRACT FROM AUTHOR]

Di-n-butyl phthalate (DBP) is a prevalent phthalate ester widely used as a plasticizer, leading to its widespread presence in various environmental matrices. This study presents an innovative microbial immobilization strategy utilizing biochar, calcium alginate (alginate-Ca, (C12H14CaO12)n), and waterborne polyurethane (WPU) composites to enhance the biodegradation efficiency of DBP. The results revealed that rice husk biochar, pyrolyzed at 300 °C, exhibits relatively safer and more stable physical and chemical properties, making it an effective immobilization matrix. Additionally, the optimal cultural conditions for Bacillus aquimaris in DBP biodegradation were identified as incubation at 30 °C and pH 7, with the supplementation of 0.15 g of yeast extract, 0.0625 g of glucose, and 1 CMC of Triton X-100. Algal biotoxicity results indicated a significant decrease in biotoxicity, as evidenced by an increase in chlorophyll a content in Chlorella vulgaris following DBP removal from the culture medium. Finally, microbial community analysis demonstrated that encapsulating B. aquimaris within alginate-Ca and WPU layers not only enhanced DBP degradation, but also prevented ecological competition from indigenous microorganisms. This novel approach showcases the potential of agricultural waste utilization and microbial immobilization techniques for the remediation of DBP-contaminated environments. [ABSTRACT FROM AUTHOR]