Ultrasonic imaging of delamination in thick CFRP laminates using an energy-compensation reverse time migration method.

In ultrasonic reflection method, the precision of defect detection in thick carbon fiber reinforced plastics (CFRP) is compromised by acoustic energy attenuation. An energy-compensation reverse time migration (ECRTM) method is proposed to identify multiple defects accurately. Forward and backward wavefields are formed using the finite element method within an anisotropic acoustic model based on the Christoffel equation and Bond transformation. To enhance the imaging quality of CFRP laminates, a novel cross-correlation imaging condition is introduced to compensate for energy dissipation caused by geometric diffusion and variations of the far-field radiation intensity at the emitter with the propagation direction. Employing ultrasonic detection technology with a multi-element array, numerical and experimental research on defect imaging was conducted, considering delamination with various sizes and positions in a multidirectional CFRP laminate. In comparison to other ultrasonic imaging methods, the near-surface artifacts in RTM images are mitigated by the far-field radiation directivity factor, while the deep information is enhanced by the geometric diffusion compensation factor in the ECRTM images. As a result, the precise position of delamination in CFRP laminates is achievable, demonstrating superior imaging capabilities, especially for deep delamination.

Thioridazine reverses trastuzumab resistance in gastric cancer by inhibiting S-phase kinase associated protein 2-mediated aerobic glycolysis.

BACKGROUND: Trastuzumab constitutes the fundamental component of initial therapy for patients with advanced human epidermal growth factor receptor 2 (HER-2)-positive gastric cancer (GC). However, the efficacy of this treatment is hindered by substantial challenges associated with both primary and acquired drug resistance. While S-phase kinase associated protein 2 (Skp2) overexpression has been implicated in the malignant progression of GC, its role in regulating trastuzumab resistance in this context remains uncertain. Despite the numerous studies investigating Skp2 inhibitors among small molecule compounds and natural products, there has been a lack of successful commercialization of drugs specifically targeting Skp2. AIM: To discover a Skp2 blocker among currently available medications and develop a therapeutic strategy for HER2-positive GC patients who have experienced progression following trastuzumab-based treatment. METHODS: Skp2 exogenous overexpression plasmids and small interfering RNA vectors were utilized to investigate the correlation between Skp2 expression and trastuzumab resistance in GC cells. Q-PCR, western blot, and immunohistochemical analyses were conducted to evaluate the regulatory effect of thioridazine on Skp2 expression. A cell counting kit-8 assay, flow cytometry, a amplex red glucose/glucose oxidase assay kit, and a lactate assay kit were utilized to measure the proliferation, apoptosis, and glycolytic activity of GC cells in vitro. A xenograft model established with human GC in nude mice was used to assess thioridazine's effectiveness in vivo. RESULTS: The expression of Skp2 exhibited a negative correlation with the sensitivity of HER2-positive GC cells to trastuzumab. Thioridazine demonstrated the ability to directly bind to Skp2, resulting in a reduction in Skp2 expression at both the transcriptional and translational levels. Moreover, thioridazine effectively inhibited cell proliferation, exhibited antiapoptotic properties, and decreased the glucose uptake rate and lactate production by suppressing Skp2/protein kinase B/mammalian target of rapamycin/glucose transporter type 1 signaling pathways. The combination of thioridazine with either trastuzumab or lapatinib exhibited a more pronounced anticancer effect in vivo, surpassing the efficacy of either monotherapy. CONCLUSION: Thioridazine demonstrates promising outcomes in preclinical GC models and offers a novel therapeutic approach for addressing trastuzumab resistance, particularly when used in conjunction with lapatinib. This compound has potential benefits for patients with Skp2-proficient tumors.

PRMT5 regulates the polysaccharide content by controlling the splicing of thaumatin-like protein in Ganoderma lucidum.

IMPORTANCE: PRMT5 contributes to secondary metabolite biosynthesis in Ganoderma lucidum. However, the mechanism through which PRMT5 regulates the biosynthesis of secondary metabolites remains unclear. In the current study, PRMT5 silencing led to a significant decrease in the biosynthesis of polysaccharides from G. lucidum through the action of the alternative splicing of TLP. A shorter TLP2 isoform can directly bind to PGI and regulated polysaccharide biosynthesis. These results suggest that PRMT5 enhances PGI activity by regulating TLP binding to PGI. The results of the current study reveal a novel target gene for PRMT5-mediated alternative splicing and provide a reference for the identification of PRMT5 regulatory target genes.

Untargeted metabolomics of saliva in pregnant women with and without gestational diabetes mellitus and healthy non-pregnant women.

Objective: The aim of this study was to compare the differences in salivary metabolites between pregnant women with gestational diabetes mellitus (GDM), healthy pregnant women (HPW), and healthy non-pregnant women (HNPW), and analyze the possible associations between the identified metabolites and gingivitis. Method: The study included women with GDM (n = 9, mean age 28.9 ± 3.6 years, mean gestational age 30.1 ± 3.2 weeks), HPW (n = 9, mean age 27.9 ± 3.0 years, mean gestational age 28.6 ± 4.7 weeks), and HNPW (n = 9, mean age 27.7 ± 2.1 years). Saliva samples were collected from all participants and were analyzed with LC-MS/MS-based untargeted metabolomic analysis. Metabolite extraction, qualitative and semi-quantitative analysis, and bioinformatics analysis were performed to identify the differential metabolites and metabolic pathways between groups. The identified differential metabolites were further analyzed in an attempt to explore their possible associations with periodontal health and provide evidence for the prevention and treatment of periodontal inflammation during pregnancy. Results: In positive ion mode, a total of 2,529 molecular features were detected in all samples, 166 differential metabolites were identified between the GDM and HPW groups (89 upregulated and 77 downregulated), 823 differential metabolites were identified between the GDM and HNPW groups (402 upregulated and 421 downregulated), and 647 differential metabolites were identified between the HPW and HNPW groups (351 upregulated and 296 downregulated). In negative ion mode, 983 metabolites were detected in all samples, 49 differential metabolites were identified between the GDM and HPW groups (29 upregulated and 20 downregulated), 341 differential metabolites were identified between the GDM and HNPW groups (167 upregulated and 174 downregulated), and 245 differential metabolites were identified between the HPW and HNPW groups (112 upregulated and 133 downregulated). A total of nine differential metabolites with high confidence levels were identified in both the positive and negative ion modes, namely, L-isoleucine, D-glucose 6-phosphate, docosahexaenoic acid, arachidonic acid, adenosine, adenosine-monophosphate, adenosine 5'-monophosphate, xanthine, and hypoxanthine. Among all pathways enriched by the upregulated differential metabolites, the largest number of pathways were enriched by four differential metabolites, adenosine, adenosine 5'-monophosphate, D-glucose 6-phosphate, and adenosine-monophosphate, and among all pathways enriched by the downregulated differential metabolites, the largest number of pathways were enriched by three differential metabolites, L-isoleucine, xanthine, and arachidonic acid. Conclusion: Untargeted metabolomic analysis of saliva samples from pregnant women with GDM, HPW, and HNPW identified nine differential metabolites with high confidence. The results are similar to findings from previous metabolomics studies of serum and urine samples, which offer the possibility of using saliva for regular noninvasive testing in the population of pregnant women with and without GDM. Meanwhile, the associations between these identified differential metabolites and gingivitis need to be further validated by subsequent studies.

Comprehensive analysis of the lncRNAs-related immune gene signatures and their correlation with immunotherapy in lung adenocarcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs)-related immune genes (lrRIGs) play a crucial role in the development and progression of lung adenocarcinoma (LUAD). However, reliable prognostic signatures based on lrRIGs have not yet been identified. METHODS: We screened lrRIGs associated with the prognosis of LUAD using The Cancer Genome Atlas (TCGA) database and then established a novel prognostic nine-gene signature composed of CD79A, INHA, SHC3, LIFR, TNFRSF11A, GPI, F2RL1, SEMA7A and WFDC2 through bioinformatic approaches. A risk score derived from this gene signature was used to divide LUAD patients into the low- and high-risk groups. The latter was confirmed to have markedly worse overall survival (O.S.). A nomogram was developed using the risk score and other independent prognostic elements, demonstrating excellent performance in predicting the O.S. rate of LUAD patients. RESULTS: We observed that the infiltration of diverse immune cell subtypes and response to immunotherapy and chemotherapy significantly differed between the low- and high-risk groups. CONCLUSIONS: Overall, stratification based on this gene signature could be used to guide better therapeutic management and improve outcomes for LUAD patients.

ARNTL inhibits the malignant behaviors of oral cancer by regulating autophagy in an AKT/mTOR pathway-dependent manner.

Current studies have shown that ARNTL, an important clock gene, plays an anticancer role and is downregulated in certain types of cancer. However, the biological functions and mechanisms of ARNTL in tumors remain largely unknown. This study aimed to elucidate how ARNTL-induced autophagy impacts the biological properties of tongue squamous cell carcinoma (TSCC) cells and the mechanisms by which ARNTL expression activates autophagy. ARNTL was stably overexpressed in TSCC cells to investigate its functions in vitro and in vivo. We found that activation of autophagy induced by ARNTL decreases cell proliferation, enhances cell death, and hinders the migratory ability of TSCC cells. Moreover, ARNTL antagonizes the AKT/mTOR pathway, which potentiates autophagy induction. The manipulation of Akt activation cancels the effects of ARNTL overexpression on the biological behaviors of TSCC cells. Furthermore, after the addition of SC79, the upregulated BAX expression due to ARNTL overexpression and downregulated expressions of BCL-2 and MMP2 were remarkably rescued. In vivo tumorigenicity assays and immunohistochemistry also confirmed that ARNTL overexpression suppresses tumor development. Our study found for the first time that ARNTL inhibits the malignant behaviors of oral cancer cells by regulating autophagy in an AKT/mTOR pathway-dependent manner, which provides a novel theoretical basis for the potential future application of ARNTL to treat patients with oral cancer.

Oral microbial communities in 5-year-old children with versus without dental caries.

BACKGROUND: Caries in young children has received more and more attention. The study of the oral microbiota may help to understand the polymicrobial etiology of dental caries. OBJECTIVES: To investigate the diversity and structure of microbial communities in saliva samples from 5-year-old children with versus without dental caries. METHODS: A total of 36 saliva samples were collected from 18 children with high caries (HB group) and from 18 children without caries (NB group). Then, 16S rDNA was amplified from bacterial samples using polymerase chain reaction, and high-throughput sequencing was performed using Illumina Novaseq platforms. RESULTS: Sequences were clustered into operational taxonomic units (OTUs), which were distributed among 16 phyla, 26 classes, 56 orders, 93 families, 173 genera, and 218 species. Firmicutes, Bacteroides, Proteobacteria, Actinobacteria, Fusobacteria, Patescibacteria, Epsilonbacteraeota, Cyanobacteria, Acidobacteria and Spirochaetes were basically the same in different groups, but their relative abundances were different. The core microbiome was defined as the species from 218 shared microbial taxa. The alpha diversity test showed that there were no significant differences in microbial abundance and diversity between the high caries and no caries groups. The results from principal coordinate analysis (PCoA) and hierarchical clustering showed that the two groups had similar microorganisms. The biomarkers of different groups were defined by LEfSe analysis to identify potential caries-related and health-related bacteria. Co-occurrence network analysis of dominant genera showed that oral microbial communities in the no caries group were more complex and aggregated than those in the high caries group. Finally, the PICRUSt algorithm was used to predict the function of the microbial communities from saliva samples. The obtained results showed that mineral absorption was greater in the no caries group than in the high caries group. BugBase was used to determine phenotypes present in microbial community samples. The obtained results showed that Streptococcus was greater in the high caries group than in the no caries group. CONCLUSION: Findings of this study provide a comprehensive understanding of the microbiological etiology of dental caries in 5-year-old children and are expected to provide new methods for its prevention and treatment.

A review on guided-ultrasonic-wave-based structural health monitoring: From fundamental theory to machine learning techniques.

The development of structural health monitoring (SHM) techniques is of great importance to improve the structural efficiency and safety. With advantages of long propagation distances, high damage sensitivity, and economic feasibility, guided-ultrasonic-wave-based SHM is recognized as one of the most promising technologies for large-scale engineering structures. However, the propagation characteristics of guided ultrasonic waves in in-service engineering structures are highly complex, which results in difficulties in developing precise and efficient signal feature mining methods. The damage identification efficiency and reliability of existing guided ultrasonic wave methods cannot meet engineering requirements. With the development of machine learning (ML), numerous researchers have proposed improved ML methods that can be incorporated into guided ultrasonic wave diagnostic techniques for SHM of actual engineering structures. To highlight their contributions, this paper provides a state-of-the-art overview of the guided-wave-based SHM techniques enabled by ML methods. Accordingly, multiple stages required for ML-based guided ultrasonic wave techniques are discussed, including guided ultrasonic wave propagation modeling, guided ultrasonic wave data acquisition, wave signal pre-processing, guided wave data-based ML modeling, and physics-based ML modeling. By placing ML methods in the context of the guided-wave-based SHM for actual engineering structures, this paper also provides insights into future prospects and research strategies.

Untargeted metabolomics of saliva in caries-active and caries-free children in the mixed dentition.

Objective: To compare the differences in salivary metabolites between caries-active and caries-free children in the mixed dentition, and explore their correlation with caries status. Methods: The study involved 20 children (aged 8-9 years) in the mixed dentition, including 10 caries-active (aged 8.6 ± 0.49years) and 10 caries-free children(aged 8.5 ± 0.5years), with a male/female ratio of 1:1. The saliva samples were collected from all children. Metabolite extraction, LC-MS/MS-based untargeted metabolomics, qualitative and semi-quantitative analysis and bioinformatics analysis were performed to identify differential metabolites between the two sample groups. The differential metabolites identified were further analyzed in an attempt to find their correlations with caries status. Results: In the positive ion mode, a total of 1606 molecular features were detected in the samples of the two groups, 189 of which were differential metabolites when comparing the caries-active group with the caries-free group, including 104 up-regulated and 85 down-regulated metabolites. In the negative ion mode, a total of 532 molecular features were detected in the samples of two groups, 70 of which were differential metabolites when comparing the caries-active group with the caries-free group, including 37 up-regulated and 33 down-regulated metabolites. In the positive ion mode, two of the top 5 up-regulated differential metabolites were found in and annotated to specific metabolic pathways, whereas in the negative ion mode, only one of the top 5 up-regulated differential metabolites was found in and annotated to specific metabolic pathways. In both the positive and negative ion modes, the top 5 down-regulated differential metabolites were both annotated to the metabolic pathways. KEGG pathway enrichment analysis of differential metabolites showed that histamine and arachidonic acid identified in the positive ion mode, as well as succinate and L-histidine identified in the negative ion mode were enriched in the top 3 significantly altered pathways. Conclusion: The enriched differential metabolites including histamine, L-histidine and succinate were correlated with the presence of dental caries, but their role in the caries process needs to be further investigated.

Effects of topical fluoride application on oral microbiota in young children with severe dental caries.

While the effect of fluoride on severe early childhood caries (S-ECC) is clear, knowledge of how it influences the oral microbiota and the consequential effects on oral health is limited. In this cohort study, we investigated the changes introduced in the oral ecosystem before and after using fluoride varnish in 54- to 66-month-old individuals (n=90: 18 children were sampled at 5 different time points). 16S rDNA was amplified from bacterial samples using polymerase chain reaction, and high-throughput sequencing was performed using Illumina MiSeq platforms. Many pronounced microbial changes were related to the effects of fluoride varnishing. The health-associated Bacteroides and Uncultured_bacterium_f_Enterobacteriaceae were enriched in the saliva microbiome following treatment with fluoride varnishing. Co-occurrence network analysis of the dominant genera showed that different groups clearly showed different bacterial correlations. The PICRUSt algorithm was used to predict the function of the microbial communities from saliva samples. The results showed that starch and sucrose metabolism was greater after fluoride use. BugBase was used to determine phenotypes present in microbial community samples. The results showed that Haemophilus and Neisseria (phylum Proteobacteria) was greater before fluoride use. We conclude that the changes in oral microbiology play a role in fluoride prevention of S-ECC.

Synthesis and evaluation of naphthalene derivatives as potent STAT3 inhibitors and agents against triple-negative breast cancer growth and metastasis.

PURPOSE: Triple-negative breast cancer (TNBC) represents the worst prognostic subtype of breast cancer and lacks targeted therapeutic drugs. Signal transducer and activator of transcription 3 (STAT3) is overexpressed and constitutively activated in TNBCs and associated with poor patient outcomes. However, no agents targeting STAT3 have been successfully developed and marketed. Selective Estrogen Receptor Modulators (SERMs) have been reported as potential inhibitors of the IL-6/STAT3 signaling pathway. Naphthalene compounds have good pharmacological activity and significant anti-cancer activity. In this study, we synthesized a new series of naphthalene derivatives with the general structure of SERM and evaluated their effects on TNBC and STAT3 signals. METHODS: A new series of compounds based on the scaffold of SERMs and an amino group were designed and screened based on the structure-activity relationship by MTT assay. The binding activity of SMY002 to STAT3 was predicted and validated by docking and SPR. The STAT3 signaling target and anti-cancer effects of SMY002 were evaluated with three TNBC cell lines and the mice transplanted tumor model. RESULTS: Among the compounds, SMY002 displayed the most potent activity, which could directly interact with STAT3 SH2-domain, and strongly inhibit the phosphorylation, dimerization, nuclear distribution, transcriptional activity, and target genes expression of STAT3. Furthermore, SMY002 markedly suppressed migration, invasion, survival, growth, and metastasis of TNBC cells in vitro and in vivo via down-regulating the expression of Cyclin D1 and MMP9. CONCLUSIONS: SMY002 can significantly inhibit the growth and metastasis of TNBC cells by targeting the STAT3 signal.

Crosstalk between heat shock factor 1 and signal transducer and activator of transcription 3 mediated by interleukin-8 autocrine signaling maintains the cancer stem cell phenotype in liver cancer.

BACKGROUND AND AIM: Liver cancer stem cells (LCSCs) cause therapeutic refractoriness and relapse in hepatocellular carcinoma. Heat shock factor 1 (HSF1) plays versatile roles in multiple cancers. However, the role of HSF1 in LCSCs is not well understood. This study investigated the function and signal mechanisms of HSF1 in maintaining LCSC phenotypes. METHODS: We established two LCSC lines, HepG2-R and HuH-7-R. Constitutive activation of HSF1 was observed in these LCSCs. Specific short hairpin RNAs (shRNAs) and chemical inhibitors were used to identify the relationship between HSF1 expression and LCSCs phenotypes. RESULTS: We revealed a concomitant activation modality involving HSF1 and STAT3 in LCSCs and liver cancer tissues. We also found that liver cancer patients whose HSF1 and STAT3 mRNA expression levels were high presented with unfavorable clinicopathological characteristics. Moreover, the secretion of interleukin-8 (IL-8) was elevated in the LCSC medium and was directly regulated by HSF1 at the transcriptional level. In turn, IL-8 activated HSF1 and STAT3 signaling, and a neutralizing IL-8 antibody inhibited HSF1 and STAT3 activity, reduced cancer stem cell marker expression, and decreased LCSC microsphere formation. Simultaneous intervention with HSF1 and STAT3 led to synergistically suppressed stemness acquisition and growth suppression in the LCSCs in vivo and in vitro. CONCLUSIONS: Our study indicates that IL-8 mediates the crosstalk between the HSF1 and Stat3 signaling pathways in LCSCs and that the combined targeting of HSF1 and STAT3 is a promising treatment strategy for patients with advanced liver cancer.

The circadian clock gene ARNTL overexpression suppresses oral cancer progression by inducing apoptosis via activating autophagy.

The study aimed to explore tumor suppressor mechanism of ARNTL from the perspective of autophagy in oral cancer. Human oral squamous carcinoma HN6 cells stably overexpressing ARNTL were established, cell viability and apoptosis were detected by CCK-8 and TUNEL assays, and intracellular autophagosomes were observed under electron microscopy. Western Blot detected expressions of Beclin1, LC3 II/I, ATG-12, P62, BAX and BCL-2. Bafilomycin A1 was used to detect autophagic flux, and Western Blot was used to detect changes of LC3II and P62 proteins. Autophinib was added to cells with ARNTL overexpression for recovery experiments, and cell proliferation and apoptosis were detected by flow cytometry. In vivo tumorigenesis experiment was used to evaluate the in vivo anti-tumor efficacy of ARNTL, and Western blot simultaneously detected ARNTL, LC3 II/I, Beclin1, P62 and ATG-12 expressions. ARNTL overexpression promoted apoptosis and autophagy and inhibited cell viability. In ARNTL-overexpressing cells, expressions of Beclin1, LC3 II/I, and BAX were significantly up-regulated, while P62 and BCL-2 expressions were decreased, and ATG-12 expression wasn't significantly changed. When the autophagy inhibitor Autophinib was used, expressions of elevated BAX and decreased BCL-2 were reversed effectively, as were decreased cell proliferation index and increased apoptosis index. An in vivo tumorigenesis assay also showed ARNTL overexpression inhibited tumor growth, and autophagy-related protein expressions were consistent with the in vitro data. The research demonstrated for the first time that ARNTL induced apoptosis and inhibited cell proliferation dependent on autophagy in oral cancer, which provides theoretical basis for potential therapeutic targets.

Upregulation of TACAN in the trigeminal ganglion affects pain transduction in acute pulpitis.

OBJECTIVE: Acute pulpitis is one of the common causes of tooth pain. TACAN (Tmem120a) is a newly identified ion channel that senses mechanical pain. In this experiment, we studied the expression of the TACAN ion channel in the trigeminal ganglia in a rat model of pulpitis to explore the correlation between the expression of this ion channel and inflammatory pain. DESIGN: Lipopolysaccharide was used to induce acute pulpitis in rats, and pulpitis was assessed histologically. The facial pain threshold of the rats was measured by the von Frey test. TACAN mRNA expression in rat dental pulp and the trigeminal nerve was measured by qPCR, and TACAN protein expression in the trigeminal ganglia was evaluated by western blot analysis and immunofluorescence. Antisense oligonucleotides were used to reduce TACAN protein expression in the trigeminal ganglia, and the change in the pain threshold in the rats with acute pulpitis was determined. RESULTS: The results showed that the TACAN transcript level in rat pulp tissue increased under inflammatory conditions, and we proved that pulpitis increased TACAN protein expression in the rat ipsilateral trigeminal ganglia. The facial pain threshold was decreased in rats with pulpitis. A short-term decrease in TACAN protein expression could improve the pain threshold. CONCLUSIONS: With the development of pulpitis after bacterial infection, the upregulation of TACAN expression in the trigeminal ganglia promoted pain sensitivity. A short-term reduction in TACAN expression relieved pain. Therefore, this study indicated that TACAN is a potential target channel for new analgesics.

Transient receptor potential vanilloid type-1 regulates periodontal disease damage via the PI3K/AKT signaling pathway.

Objectives: This study aimed to investigate the function of transient receptor potential vanilloid 1 (TRPV1) in regulating periodontal lesions. In addition, we explored the underlying mechanism of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway. Materials and Methods: Lipopolysaccharide (LPS) stimulation of human periodontal ligament cells (HPDLCs) was used to construct a periodontitis cell model, and experimental periodontitis (EP) rats were established by ligation. The mechanism by which TRPV1 regulates periodontitis was further verified by injecting the TRPV1 agonist capsaicin (CPS) and antagonist capsazepine (CPZ) into the gingiva of rats; the alveolar bone losses in each group were measured by stereomicroscopy. Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting (WB) were used to research the expression of TRPV1 and proinflammatory cytokines, and WB was performed to test the phosphorylation of PI3K and AKT. Results: In vitro experiments showed that LPS induced the upregulation of TRPV1 and proinflammatory cytokines and promoted the phosphorylation of PI3K and AKT proteins in HPDLCs, which was consistent with their expression in the rat periodontitis model. Moreover, in vivo studies indicated that CPZ had anti-inflammatory effects through the PI3K/AKT pathway and inhibited bone loss induced by periodontal ligation in rats, while CPS had the opposite effect. Conclusion: TRPV1 was involved in the process of alveolar bone defects and the inflammatory response in rats with periodontitis induced by ligation. Its mechanism might be related to the phosphorylation of related proteins in the PI3K/AKT signaling pathway.

Off-Grid DOA Estimation Using Sparse Bayesian Learning for MIMO Radar under Impulsive Noise.

Direction of arrival (DOA) estimation is an essential and fundamental part of array signal processing, which has been widely used in radio monitoring, autonomous driving of vehicles, intelligent navigation, etc. However, it remains a challenge to accurately estimate DOA for multiple-input multiple-output (MIMO) radar in impulsive noise environments. To address this problem, an off-grid DOA estimation method for monostatic MIMO radar is proposed to deal with non-circular signals under impulsive noise. In the proposed method, firstly, based on the property of non-circular signal and array structure, a virtual array output was built and a real-valued sparse representation for the signal model was constructed. Then, an off-grid sparse Bayesian learning (SBL) framework is proposed and further applied to the virtual array to construct novel off-grid sparse model. Finally, off-grid DOA estimation was realized through the solution of the sparse reconstruction with high accuracy even in impulsive noise. Numerous simulations were performed to compare the algorithm with existing methods. Simulation results verify that the proposed off-grid DOA method enables evident performance improvement in terms of accuracy and robustness compared with other works on impulsive noise.

LIPUS Promotes Endothelial Differentiation and Angiogenesis of Periodontal Ligament Stem Cells by Activating Piezo1.

Background and Objectives: Low-intensity pulsed ultrasound (LIPUS) promotes differentiation and regulates biological functions of various stem cells, but its effect on the endothelial differentiation of periodontal ligament stem cells (PDLSCs) is unclear. This study investigated the effect of LIPUS on endothelial differentiation and angiogenesis in PDLSCs and the role of the mechanically sensitive ion channel Piezo1 in this process. Methods and Results: PDLSCs obtained from healthy people were used for endothelial induction, and 10 µg/ml lipopolysaccharide (LPS) was used to simulate the inflammatory state. The induced cells were treated with LIPUS (50 mW/cm2, 1.5 MHz) to study its effect on the endothelial differentiation of PDLSCs and the tube formation of differentiated cells. PCR, flow cytometry, immunofluorescence, and Matrigel tube formation assays were used to detect the differentiation and tube formation of PDLSCs. GsMTx4 was used to inhibit the expression of Piezo1, and the role of the Piezo1 pathway in the endothelial differentiation and microvascular formation of PDLSCs after LIPUS treatment was studied. The data showed that LIPUS increased endothelial differentiation and angiogenesis in PDLSCs under inflammatory or noninflammatory conditions. The use of an inhibitor weakened the effect of LIPUS. Conclusions: This study demonstrated that LIPUS can activate the expression of Piezo1 and promote the endothelial differentiation and microvascular formation of PDLSCs.

Biotin attenuates heat shock factor 4b transcriptional activity by lysine 444 biotinylation.

Genetic mutations in HSF4 cause congenital cataracts. HSF4 exhibits both positive and negative regulation on the transcription of heat shock and non-heat shock proteins during lens development, and its activity is regulated by posttranslational modifications. Biotin is an essential vitamin that regulates gene expression through protein biotinylation. In this paper, we report that HSF4b is negatively regulated by biotinylation. Administration of biotin or ectopic bacterial biotin ligase BirA increases HSF4b biotinylation at its C-terminal amino acids from 196 to 493. This attenuates the HSF4b-controlled expression of αB-crystallin in both lens epithelial cells and tested HEK293T cells. HSF4b interacts with holocarboxylase synthetase (HCS), a ubiquitous enzyme for catalyzing protein biotinylation in mammal. Ectopic HA-HCS expression downregulates HSF4b-controlled αB-crystallin expression. Lysine-mutation analyses indicate that HSF4b/K444 is a potential biotinylation site. Mutation K444R reduces the co-precipitation of HSF4b by streptavidin beads and biotin-induced reduction of αB-crystallin expression. Mutations of other lysine residues such as K207R/K209R, K225R, K288R, K294R and K355R in HSF4's C-terminal region do not affect HSF4's expression level and the interaction with streptavidin, but they exhibit distinct regulation on αB-crystallin expression through different mechanisms. HSF4/K294R leads to upregulation of αB-crystallin expression, while mutations K207R/K209R, K225R, K288R, K255R and K435R attenuate HSF4's regulation on αB-crystallin expression. K207R/K209R blocks HSF4 nuclear translocation, and K345R causes HSF4 destabilization. Taken together, the data reveal that biotin maybe a novel factor in modulating HSF4 activity through biotinylation.

Cloning and characterization of phosphoglucose isomerase in Lentinula edodes.

Phosphoglucose isomerase (PGI) is a key enzyme that participates in polysaccharide synthesis, which is responsible for the interconversion of glucose-6-phosphate (G-6-P) and fructose-6-phosphate (F-6-P), but there is little research focusing on its role in fungi, especially in higher basidiomycetes. The pgi gene was cloned from Lentinula edodes and named lepgi. Then, the lepgi-silenced strains were constructed by RNA interference. In this study, we found that lepgi-silenced strains had significantly less biomass than the wild-type (WT) strain. Furthermore, the extracellular polysaccharide (EPS) and intracellular polysaccharide (IPS) levels increased 1.5- to 3-fold and 1.5-fold, respectively, in lepgi-silenced strains. Moreover, the cell wall integrity in the silenced strains was also altered, which might be due to changes in the compounds and structure of the cell wall. The results showed that compared to WT, silencing lepgi led to a significant decrease of approximately 40% in the ß-1,3-glucan content, and there was a significant increase of 2-3-fold in the chitin content. These findings provide support for studying the biological functions of lepgi in L. edodes.

Multi-Mode Ultrasonic Guided Waves Based Damage Detection in L-Bars with Asymmetric Cross-Section with Sum of Multiple Signals Method.

Bars are significant load-carrying components in engineering structures. In particular, L-bars are typical structural components commonly used in truss structures and have typical irregular asymmetric cross-sections. To ensure the safety of load-carrying bars, much research has been done for non-destructive testing (NDT). Ultrasonic guided waves have been widely applied in various NDT techniques for bars as a result of the long-range propagation, low attenuation, and high sensitivity to damages. Though good for inspection of ultrasonic guided waves in symmetric cross-section bar-like structures, the application in asymmetric ones lacks further research. Moreover, traditional damage detection in bars using ultrasonic guided waves usually depends on a single-mode at a lower frequency with lower sensitivity and accuracy. To make full use of all frequencies and modes, a multi-mode characteristic-based damage detection method is presented with the sum of multiple signals (SoM) strategy for L-bars with asymmetric cross-section. To control the desired mode in multi-mode ultrasonic guided waves, excitation optimization and weighted gathering are carried out by the analysis of the semi-analytical finite element (SAFE) method and the normal mode expansion (NME) method. An L-bar example with the asymmetric cross-section of 35 mm × 20 mm × 3 mm is used to specialize the proposed method, and some finite element (FE) models have been simulated to validate the mode control. In addition, one PZT is applied as a contrast in order to validate the multielement mode control. Then, more FE simulations experiments for damage detection have been performed to validate the damage detection method and verify the improvement in detection accuracy and damage sensitivity.