Da-Chai-Hu-Tang Formula inhibits the progression and metastasis in HepG2 cells through modulation of the PI3K/AKT/STAT3-induced cell cycle arrest and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Da-Chai-Hu-Tang (DCHT), a Chinese traditional herbal compound, has been utilized for the treatment of Hepatic diseases in China for over 1800 years. The DCHT formula contains eight herbals: Bupleurum chinense DC. (chaihu), Scutellaria baicalensis Georgi (huangqin), Paeonia lactiflora Pall. (baishao), Pinellia ternata (Thunb.) Makino (banxia), Rheum officinale Baill. (dahuang), Citrus × aurantium L. (zhishi), Zingiber officinale Roscoe (shengjiang), Ziziphus jujuba Mill. (dazao). Clinical studies have demonstrated the effectiveness of DCHT in hepatocellular carcinoma (HCC) and its ability to enhance the immunity of patients with hepatocellular carcinoma. A total of 20 Chinese articles have been published on the use of DCHT in treating HCC. AIM OF THE STUDY: The study aimed to validate the effect of DCHT in HCC cells and to identify related targets (TP53, AKT1, BCL2, STAT3) in treating HCC by DCHT in vitro experiments. MATERIALS AND METHODS: Cell proliferation and migration were investigated in vitro. Flow cytometry analysis was used to evaluate the cell cycle and apoptosis. Apoptotic bodies in HepG2 cells were observed using a confocal microscope. Biochemical detection was employed to analyze LDH release, MDA levels, and SOD levels. Bioinformatics analysis was used to predict core targets between DCHT and HCC, as well as potential signaling pathways. The protein levels of metastasis-associated, apoptosis, and PI3K, AKT, p-AKT, and STAT3 were further determined through Western blotting. RESULTS: Following treatment with DCHT, the inhibition of viability, migration, and G2/M arrest was observed in HepG2 cells. Flow cytometry analysis and Morphological apoptosis studies provided evidence that DCHT could induce apoptosis in HepG2 cells. Biochemical detection revealed that DCHT could increase LDH release and the level of MDA, and inhibit the viability of the SOD. Bioinformatics analysis identified key targets such as TP53, AKT1, BCL2, STAT3. The PI3K/AKT/STAT3 signaling pathway emerged as a critical pathway in the KEGG enrichment analysis. Western blotting results indicated that DCHT could enhance the expression of E-cadherin, p53, and Bax, while reducing the content of N-cadherin, Bcl-2, PI3K, p-AKT, AKT1, and STAT3. CONCLUSIONS: The results proved that DCHT could inhibit the progression and metastasis of HCC by regulating the expression of E-cadherin, N-cadherin, p53, Bax, Bcl-2, PI3K, p-AKT, AKT, and STAT3 through the PI3K/AKT/STAT3 signaling pathway.

SEB-YOLO: An Improved YOLOv5 Model for Remote Sensing Small Target Detection.

Due to the limited semantic information extraction with small objects and difficulty in distinguishing similar targets, it brings great challenges to target detection in remote sensing scenarios, which results in poor detection performance. This paper proposes an improved YOLOv5 remote sensing image target detection algorithm, SEB-YOLO (SPD-Conv + ECSPP + Bi-FPN + YOLOv5). Firstly, the space-to-depth (SPD) layer followed by a non-strided convolution (Conv) layer module (SPD-Conv) was used to reconstruct the backbone network, which retained the global features and reduced the feature loss. Meanwhile, the pooling module with the attention mechanism of the final layer of the backbone network was designed to help the network better identify and locate the target. Furthermore, a bidirectional feature pyramid network (Bi-FPN) with bilinear interpolation upsampling was added to improve bidirectional cross-scale connection and weighted feature fusion. Finally, the decoupled head is introduced to enhance the model convergence and solve the contradiction between the classification task and the regression task. Experimental results on NWPU VHR-10 and RSOD datasets show that the mAP of the proposed algorithm reaches 93.5% and 93.9%respectively, which is 4.0% and 5.3% higher than that of the original YOLOv5l algorithm. The proposed algorithm achieves better detection results for complex remote sensing images.

Diagnostic and prognostic performance of artificial intelligence-based fully-automated on-site CT-FFR in patients with CAD.

Currently, clinically available coronary CT angiography (CCTA) derived fractional flow reserve (CT-FFR) is time-consuming and complex. We propose a novel artificial intelligence-based fully-automated, on-site CT-FFR technology, which combines the automated coronary plaque segmentation and luminal extraction model with reduced order 3 dimentional (3D) computational fluid dynamics. A total of 463 consecutive patients with 600 vessels from the updated China CT-FFR study in Cohort 1 undergoing both CCTA and invasive fractional flow reserve (FFR) within 90 d were collected for diagnostic performance evaluation. For Cohort 2, a total of 901 chronic coronary syndromes patients with index CT-FFR and clinical outcomes at 3-year follow-up were retrospectively analyzed. In Cohort 3, the association between index CT-FFR from triple-rule-out CTA and major adverse cardiac events in patients with acute chest pain from the emergency department was further evaluated. The diagnostic accuracy of this CT-FFR in Cohort 1 was 0.82 with an area under the curve of 0.82 on a per-patient level. Compared with the manually dependent CT-FFR techniques, the operation time of this technique was substantially shortened by 3 times and the number of clicks from about 60 to 1. This CT-FFR technique has a highly successful (> 99%) calculation rate and also provides superior prediction value for major adverse cardiac events than CCTA alone both in patients with chronic coronary syndromes and acute chest pain. Thus, the novel artificial intelligence-based fully automated, on-site CT-FFR technique can function as an objective and convenient tool for coronary stenosis functional evaluation in the real-world clinical setting.

PnNAC2 promotes the biosynthesis of Panax notoginseng saponins and induces early flowering.

KEY MESSAGE: PnNAC2 positively regulates saponin biosynthesis by binding the promoters of key biosynthetic genes, including PnSS, PnSE, and PnDS. PnNAC2 accelerates flowering through directly associating with the promoters of FT genes. NAC transcription factors play an important regulatory role in both terpenoid biosynthesis and flowering. Saponins with multiple pharmacological activities are recognized as the major active components of Panax notoginseng. The P. notoginseng flower is crucial for growth and used for medicinal and food purposes. However, the precise function of the P. notoginseng NAC transcription factor in the regulation of saponin biosynthesis and flowering remains largely unknown. Here, we conducted a comprehensive characterization of a specific NAC transcription factor, designated as PnNAC2, from P. notoginseng. PnNAC2 was identified as a nuclear-localized protein with transcription activator activity. The expression profile of PnNAC2 across various tissues mirrored the accumulation pattern of total saponins. Knockdown experiments of PnNAC2 in P. notoginseng calli revealed a significant reduction in saponin content and the expression level of pivotal saponin biosynthetic genes, including PnSS, PnSE, and PnDS. Subsequently, Y1H assays, dual-LUC assays, and electrophoretic mobility shift assays (EMSAs) demonstrated that PnNAC2 exhibits binding affinity to the promoters of PnSS, PnSE and PnDS, thereby activating their transcription. Additionally, an overexpression assay of PnNAC2 in Arabidopsis thaliana witnessed the acceleration of flowering and the induction of the FLOWERING LOCUS T (FT) gene expression. Furthermore, PnNAC2 demonstrated the ability to bind to the promoters of AtFT and PnFT genes, further activating their transcription. In summary, these results revealed that PnNAC2 acts as a multifunctional regulator, intricately involved in the modulation of triterpenoid saponin biosynthesis and flowering processes.

Efficacy and safety of fractional carbon dioxide laser followed by 5-aminolevulinic acid photodynamic therapy for keloids.

BACKGROUND: Keloids are aggressive fibroproliferative disorders that cause aesthetic and functional damage. Photodynamic therapy (PDT) has shown promise as a novel treatment for keloids. However, the limited penetration of 5-aminolevulinic acid (ALA) and unsatisfactory outcomes in dense scars hinder its effectiveness as a monotherapy. The objective of this study is to assess the efficacy and safety of fractional CO2 laser followed by 5-ALA PDT for keloids. METHODS: A total of 12 patients with keloid were included in our study. Each lesion was pretreated by fractional CO2 laser with 26-28 W to create microthermal zones. After topical application of 5-ALA solution, an irradiation of 635 nm red light with 120 J/cm2 was performed. The treatment was repeated at least every 2 weeks. Efficacy and safety were evaluated using the Vancouver Scar Scale (VSS), the Visual Analogue Scale (VAS) for keloid-related symptoms and documentation of postoperative complications. Statistical analysis was performed to compare VSS and keloid-related symptom VAS scores of the baseline and final treatment sessions. RESULTS: The final treatment resulted in a statistically significant decrease in all parameters of VSS and VAS for pruritus and pain compared to the baseline. Except for postoperative hyperpigmentation, no infections, scar aggravation, or recurrence were observed during at least 6 months of follow-up. Overall, patients expressed a high level of satisfaction with the treatment outcome. CONCLUSIONS: Fractional CO2 laser followed by 5-ALA PDT is a promising method for treating keloids. However, its synergetic effects need to be validated through clinical trials involving larger patient cohorts.

SiamHSFT: A Siamese Network-Based Tracker with Hierarchical Sparse Fusion and Transformer for UAV Tracking.

Due to high maneuverability as well as hardware limitations of Unmanned Aerial Vehicle (UAV) platforms, tracking targets in UAV views often encounter challenges such as low resolution, fast motion, and background interference, which make it difficult to strike a compatibility between performance and efficiency. Based on the Siamese network framework, this paper proposes a novel UAV tracking algorithm, SiamHSFT, aiming to achieve a balance between tracking robustness and real-time computation. Firstly, by combining CBAM attention and downward information interaction in the feature enhancement module, the provided method merges high-level and low-level feature maps to prevent the loss of information when dealing with small targets. Secondly, it focuses on both long and short spatial intervals within the affinity in the interlaced sparse attention module, thereby enhancing the utilization of global context and prioritizing crucial information in feature extraction. Lastly, the Transformer's encoder is optimized with a modulation enhancement layer, which integrates triplet attention to enhance inter-layer dependencies and improve target discrimination. Experimental results demonstrate SiamHSFT's excellent performance across diverse datasets, including UAV123, UAV20L, UAV123@10fps, and DTB70. Notably, it performs better in fast motion and dynamic blurring scenarios. Meanwhile, it maintains an average tracking speed of 126.7 fps across all datasets, meeting real-time tracking requirements.

In Situ SEM, TEM, EBSD Characterization of Nucleation and Early Growth of Pure Fe/Pure Al Intermetallic Compounds.

The nucleation and growth processes of pure Fe/pure Al intermetallic compounds (IMCs) during heat treatment at 380 °C and 520 °C were observed through in situ scanning electron microscopy (SEM). The size of the IMCs were statistically analyzed using image analysis software. The types and distribution of IMCs were characterized using transmission electron microscopy (TEM) and electron backscattering diffraction (EBSD). The results showed that: at 380 °C, the primary phase of the Fe/Al composite intermetallic compounds was Fe4Al13, formed on the Fe side and habituated with Fe. The IMC was completely transformed from the initial Fe4Al13 to the most stable Fe2Al5, and the Fe2Al5 was the habitus with Fe during the process of holding at 380 °C for 15 min to 60 min. At 380 °C, the initial growth rate of the IMC was controlled by reaction, and the growth rate of the thickness and horizontal dimensions was basically the same as 0.02-0.17 µm/min. When the IMC layer thickness reached 4.5 µm, the growth rate of the thickness changed from reaction control to diffusion control and decreased to 0.007 µm/min. After heat treatment at 520 °C (≤20 min), the growth of IMC was still controlled by the reaction, the horizontal growth rate was 0.53 µm/min, the thickness growth rate was 0.23 µm/min, and the main phase of the IMC was the Fe2Al5 phase at 520 °C/20 min.

The overall and domain-specific quality of life of Chinese community-dwelling older adults: the role of intrinsic capacity and disease burden.

Objective: This study aimed to investigate the impact of the different domains of intrinsic capacity (IC) and chronic disease burden on health-related quality of life (HRQoL) and domain-specific HRQoL in Chinese community-dwelling older adults. Design: A cross-sectional observational study of a community-based cohort. Participants: We evaluated Chinese older adults (n = 429, mean age, 72.91 ± 7.014 years; female proportion, 57.30%). Measurements: IC contains five domains, namely locomotion, vitality, cognition, psychological, and sensory capacity. Locomotion dysfunction was defined as grip and/or gait decline. Vitality decline was defined if two of the following three parameters were present: fatigue, physical inactivity, and weight loss or overweight. Cognition was classified into normal cognition, pre-mild cognitive impairment (pre-MCI), and MCI according to the normative z-scores of the neuropsychological test battery. Psychological dysfunction was diagnosed based on depressive symptoms. Sensory dysfunction was defined as hearing and/or vision impairment. HRQoL was assessed using the AQoL-8D scale, which comprised physical (including independent living, senses, and pain) and psychosocial (including mental health, happiness, self-worth, coping, and relationships) dimensions. Low HRQoL (HRQoL score or subscores in the highest quintile) was used as a dependent variable in logistic regression analyses adjusted for demographic, health-related, and psychological confounders. Results: Sensory impairment was an independent determinant of senses, and locomotion impairment was significantly associated with overall HRQoL, independent living, and pain in the physical dimension of HRQoL. Cognition was an independent determinant of the senses. Vitality was independently associated with overall HRQoL, senses, and pain in the physical dimension and mental health and relationships in the psychological dimension of HRQoL. The psychological domain of IC was independently associated with overall and domain-specific HRQoL apart from senses after adjustment for all confounders. The number of multimorbidities mainly had a significant impact on independent living after adjustment for all confounders. Conclusion: IC domains and chronic disease burden had heterogeneous influences on overall and domain-specific HRQoL. The impairment of sensory and locomotion domains had a synergistic impact on the overall and physical dimensions of HRQoL. The vitality and psychological domains of IC had more profound effects on HRQoL. Older people with high morbidity might have a higher risk of poor independent living.

A novel physics-based model for fast computation of blood flow in coronary arteries.

Blood flow and pressure calculated using the currently available methods have shown the potential to predict the progression of pathology, guide treatment strategies and help with postoperative recovery. However, the conspicuous disadvantage of these methods might be the time-consuming nature due to the simulation of virtual interventional treatment. The purpose of this study is to propose a fast novel physics-based model, called FAST, for the prediction of blood flow and pressure. More specifically, blood flow in a vessel is discretized into a number of micro-flow elements along the centerline of the artery, so that when using the equation of viscous fluid motion, the complex blood flow in the artery is simplified into a one-dimensional (1D) steady-state flow. We demonstrate that this method can compute the fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA). 345 patients with 402 lesions are used to evaluate the feasibility of the FAST simulation through a comparison with three-dimensional (3D) computational fluid dynamics (CFD) simulation. Invasive FFR is also introduced to validate the diagnostic performance of the FAST method as a reference standard. The performance of the FAST method is comparable with the 3D CFD method. Compared with invasive FFR, the accuracy, sensitivity and specificity of FAST is 88.6%, 83.2% and 91.3%, respectively. The AUC of FFRFAST is 0.906. This demonstrates that the FAST algorithm and 3D CFD method show high consistency in predicting steady-state blood flow and pressure. Meanwhile, the FAST method also shows the potential in detecting lesion-specific ischemia.

Marein reduces lipid levels via modulating the PI3K/AKT/mTOR pathway to induce lipophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: The capitulum of Coreopsis tinctoria Nutt. (CT, Xue-Ju in Chinese) is a precious medicine in Xinjiang Uygur Autonomous region of China. The Coreopsis tinctoria Nutt. is used to prevent and treat dyslipidemia, coronary heart disease, etc. Recent studies have shown that its extract has a pharmacological effect on hyperlipidemia and hyperglycemia. AIM OF THE STUDY: The study aimed to systematically evaluate the lipid-lowering activity of CT through a mice model of hyperlipidemia and a human hepatoma G2 (HepG2) cells model of lipid accumulation, and to investigate its main active components and mechanism. MATERIALS AND METHODS: Biochemical analysis of blood/liver lipids and liver histopathology were used to evaluate the effect of the aqueous extract of Coreopsis tinctoria Nutt. (AECT) on hyperlipidemia mice. High-performance liquid chromatography (HPLC) analysis was used to identify the main components in the AECT. Oil red O staining, immunofluorescence, western blotting, and determination of the total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were used to further study the effect and potential mechanism of the AECT main components on sodium oleate-induced lipid accumulation in HepG2 cells. RESULTS: We confirmed the lipid-lowering activity of the aqueous extract and further identified flavonoids as its main components. Among them, five Coreopsis tinctoria Nutt. flavonoids mixture (FM) significantly reduced lipid droplet area, lipid content, TC, TG, and LDL-C levels, and elevated HDL-C levels in HepG2 cells induced by sodium oleate. Furthermore, they increased lipophagy in HepG2 lipid-accumulating cells, while decreasing the ratio of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR. Most importantly, marein may be a key component. CONCLUSIONS: Our study demonstrated that AECT, with flavonoids as the main component, can improve diet-induced hyperlipidemia in obese mice. Among the main five flavonoids, marein plays a key role in promoting lipophagy by regulating the PI3K/AKT/mTOR pathway, resulting in a lipid-lowering effect.

[Precise application of Beichaihu and Nanchaihu in classical formulas].

To maintain the precision and stability of the efficacy of classical formulas, this study compared the origins and specifications of Bupleuri Radix and revealed the precise application regularity of Bupleurum chinense(Beichaihu) and Bupleurum scorzonerifolium(Nanchaihu) in classical formulas. The efficacy and indications of formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases(Shang Han Za Bing Lun) were investigated. The difference in the efficacy of Bupleuri Radix as well as the differences in the chemical composition, and liver-protecting and lipid-lowering effects of the decoctions of Beichaihu and Nanchaihu were analyzed with LC-MS technology based on the CCl_4-induced liver injury model in mice and sodium oleate-induced HepG2 hyperlipidemia cell model. The results showed that seven classical formulas with Bupleuri Radix as the sovereign drug in the Treatise on Cold Damage and Miscellaneous Diseases were mainly used in the treatment of digestive, metabolic, immune, circulatory, and other diseases. Bupleuri Radix mainly played the functions of protecting the liver, benefiting the gallbladder, and lowering the lipid, and had different focuses in different formulas. There were 14 differential components in the decoctions of Beichaihu and Nanchaihu, and the chemical structures of 11 components were identified, including 10 saponins and one flavonoid. The results of the liver-protecting efficacy experiment showed that compared with the Nanchaihu decoction, Beichaihu decoction could reduce the serum aspartate aminotransferase(AST) activity in liver injury model mice(P<0.01). The results of the lipid-lowering efficacy experiment proved that Beichaihu and Nanchaihu decoctions both showed highly significant differences in lowering the total cholesterol(TC) and triglyceride(TG) content in HepG2 cells(P<0.01), and Nanchaihu decoction was superior to Beichaihu decoction in lowering the lipid. The results of this study preliminarily proved that there were differences in chemical composition, and liver-protecting and lipid-lowering effects of Beichaihu and Nanchaihu decoctions, indicating that it was necessary to determine the precise origin of Bupleuri Radix in the clinical formulation of traditional Chinese medicine. The study provides a scientific basis for both precise clinical medication and purpose-based accurate quality evaluation of traditional Chinese medicine in clinical application.

The crude extract from the flowers of Trollius chinensis Bunge exerts anti-influenza virus effects through modulation of the TLR3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The flowers of Trollius chinensis Bunge (Ranunculaceae) is a traditional Chinese medicine used to treat various inflammatory diseases, including upper respiratory infections, chronic tonsillitis, and pharyngitis. Recently, there has been growing research on the antiviral role of the flowers of T. chinensis Bunge. However, little is known about its anti-influenza virus effects and the underlying mechanisms. AIM OF THE STUDY: This study aims to evaluate the therapeutic effects of the crude extract from the flowers of T. chinensis Bunge (CEFTC) on mice infected with influenza virus. We further explored its mechanism by detecting the expression of vital proteins (TLR3, TBK1, TAK1, IKKα, IRF3, and IFN-ß) related to TLR3 signaling pathway. MATERIALS AND METHODS: Mice were infected with influenza A virus (H1N1) through the nasal cavity and were intragastrically administered CEFTC at the dose of 0.2 mg/g once daily. The therapeutic effects of CEFTC were evaluated by blood cell count, lung index, spleen index, alveolar lavage fluid testing, and HE staining. Network pharmacology analysis predicted the potential signaling pathway between the flowers of T. chinensis Bunge and pneumonia. The expression of TLR3, TBK1, TAK1, IKKα, IRF3, and IFN-ß in lung tissues were examined by Western blot assay. In addition, the immunofluorescence assay was applied to assess the effect of CEFTC on the distribution of IRF3 and IFN-ß between nuclei and cytoplasm. RESULTS: Compared with the infected group, the lung index was markedly reduced, and the pathological damage of the lungs was also attenuated in the CEFTC treatment group. The network pharmacology analysis indicated that the NF-κB pathway was a potential signaling pathway in the flowers of T. chinensis Bunge for the treatment of pneumonia, TLR3, IRF3, and TBK1 were crucial targets associated with pneumonia. Western blot assay demonstrated that in the high-dose virus infected group, CEFTC reduced the expression of TLR3, TAK1, TBK1, and IRF3. Furthermore, CEFTC could increase the nuclear distribution of IRF3 in alveolar epithelial cells after virus infection. CONCLUSIONS: These results suggested that different doses of influenza virus could cause varying infection symptoms in mice. Moreover, CEFTC could exert anti-influenza virus effects by regulating the expression of TLR3, IRF3, IFN-ß, TAK1, and TBK1 in the TLR3 signaling pathway.

M1­like tumor­associated macrophages enhance proliferation and anti­apoptotic ability of liver cancer cells via activating the NF­κB signaling pathway.

Liver cancer is the second leading cause of cancer­associated death worldwide. The present study aimed to evaluate the infiltration of M1­like tumor­associated macrophages (TAMs) and explore the role of infiltration of M1­like TAMs in the proliferation and apoptosis evasion of liver cancer cells. Furthermore, the association between M1­like TAM and the efficacy of postoperative transcatheter arterial chemoembolization (TACE) for patients with liver cancer was investigated. The levels of CD68, human leukocyte antigen­DR and phosphorylated NF­κB (p­)p65 were detected by western blot analysis and immunohistochemistry. Cell cycle analysis, MTT and clonogenic assays were utilized to investigate the proliferation of liver cancer cells. It was indicated that M1­like TAM increased the p­p65/p65 ratio in liver cancer cells and promoted cell proliferation. Furthermore, JSH­23, an inhibitor that prevents p65 from entering the nucleus, decreased the proliferation of liver cancer cells in M1­like TAM­conditioned medium. In addition, M1­like TAM increased the number of liver cancer cells in the S and G2/M phases of the cell cycle and also upregulated the expression levels of cyclin­dependent kinase (CDK)1, CDK2 and cyclin D1. By contrast, M1­like TAM decreased the expression level of p21. Through these effects, the anti­apoptotic ability of liver cancer cells was enhanced. Of note, JSH­23 reversed these changes related to the cell cycle, anti­apoptotic ability and the expression levels of proteins induced by M1­like TAM in liver cancer cells. In conclusion, the infiltration of M1­like TAM in liver tissue negatively influenced the efficacy of postoperative TACE for patients with liver cancer.

Association between age-related hearing loss with tinnitus and cognitive performance in older community-dwelling Chinese adults.

AIM: To examine how the severity of age-related hearing loss (ARHL) and tinnitus or the presentation of ARHL with tinnitus is associated with overall cognition, in terms of specific cognitive domains in older community-dwelling Chinese adults. METHODS: The study recruited 429 participants aged ≥58 years (mean age, 72.91 ± 7.014 years; female proportion, 57.30%), excluding those with dementia, disability, and severe mental illness. Patients were classified into normal cognition, pre-mild cognitive impairment (pre-MCI), and MCI according to the normative z-scores of neuropsychological test battery. The severity of ARHL and tinnitus was measured by pure-tone audiometry and the Tinnitus Handicap Inventory. Cognitive impairment and low functions in specific cognitive domains were used as dependent variables in multiple regression analyses adjusted for covariates. RESULTS: ARHL severity was positively associated with MCI and low executive function, delayed memory, and language function. Only individuals with mild (odds ratio (OR) 1.791; CI, 0.952-3.373; P = 0.071), and moderate and the disaster tinnitus (OR, 2.493; CI, 0.982-6.328; P = 0.055) were marginally associated with increased odds of MCI in model 1. Individuals with ARHL and tinnitus (OR, 3.888, CI = 1.481-10.205; OR, 4.471, CI = 1.636-12.219) were independently associated with high risk for MCI in models 1 and 2. CONCLUSIONS: ARHL severity and the presentation of ARHL or ARHL with tinnitus were associated with overall cognition. ARHL severity was independently associated with executive function, delayed memory, and language function. The association between tinnitus severity and cognition is not clear. But the group with ARHL and tinnitus is a high-risk group with cognitive impairment. CLINICALTRIALS: gov identifier: NCT2017K020.

Transformer Feature Enhancement Network with Template Update for Object Tracking.

This paper proposes a tracking method combining feature enhancement and template update, aiming to solve the problems of existing trackers lacking global information attention, weak feature characterization ability, and not being well adapted to the changing appearance of the target. Pre-extracted features are enhanced in context and on channels through a feature enhancement network consisting of channel attention and transformer architectures. The enhanced feature information is input into classification and regression networks to achieve the final target state estimation. At the same time, the template update strategy is introduced to update the sample template judiciously. Experimental results show that the proposed tracking method exhibits good tracking performance on the OTB100, LaSOT, and GOT-10k benchmark datasets.

Cocktail of Astragalus Membranaceus and Radix Trichosanthis Suppresses Melanoma Tumor Growth and Cell Migration Through Regulation of Akt-Related Signaling Pathway.

Background: Malignant melanoma has high morbidity and mortality and limited treatment options. Traditional Chinese medicine has great potential in the clinical therapy of cancer, and the theory of compatibility is one core content of Chinese medical theory. Astragalus Membranaceus and Radix Trichosanthis are clinically effective for the treatment of various cancers. Methods: We verified the effects of AMD, RTD, and their "cocktail" on melanoma model in vitro and in vivo and the mechanism of its effect on the Akt-related signaling pathway by network pharmacology, MTT, flow cytometry, LDH, SOD, MDA assay, and Western blot. Results: The network pharmacology analysis indicated that the PI3K-Akt pathway plays a crucial role in the treatment of malignant melanoma with these two herbs. In addition, AMD, RTD, and their "cocktail" could inhibit the proliferation of A375 cells by reducing the survival rate in a concentration-dependent manner and by regulating the cell cycle, and the compatibility of two herbs also could inhibit melanoma growth. They could, respectively, induce apoptosis and inhibit migration by affecting the expression of Bcl-2, Bax, p53, snail, E-cadherin, and N-cadherin. Furthermore, LDH activity was decreased, while SOD increased and MDA reduced. The factors of the Akt-related signaling pathway, Akt and p-Akt, were decreased. Conclusion: This study showed that AMD, RTD, and their "cocktail" could regulate cell proliferation, apoptosis, and metastasis in A375 cells through the suppression of the Akt-related signaling pathway, and the "cocktail" groups had detoxification and additive effects. The best compatibility of the two herbs also can inhibit tumor growth and metastasis in vivo.

miR-155: An Important Role in Inflammation Response.

MicroRNAs (miRNAs) are a class of small, mature, noncoding RNA that lead to posttranscriptional gene silencing to regulate gene expression. miRNAs are instrumental in biological processes such as cell development, cell differentiation, cell proliferation, and cell apoptosis. The miRNA-mediated gene silencing is an important part of the regulation of gene expression in many kinds of diseases. miR-155, one of the best-characterized miRNAs, has been found to be closely related to physiological and pathological processes. What is more, miR-155 can be used as a potential therapeutic target for inflammatory diseases. We analyze the articles about miR-155 for nearly five years, review the advanced study on the function of miR-155 in different inflammatory cells like T cells, B cells, DCs, and macrophages, and then summarize the biological functions of miR-155 in different inflammatory cells. The widespread involvement of miR-155 in human diseases has led to a novel therapeutic approach between Chinese and Western medicine.

MDA5 expression is associated with TGF-ß-induced fibrosis: potential mechanism of interstitial lung disease in anti-MDA5 dermatomyositis.

OBJECTIVES: This study aimed to investigate the high-resolution CT (HRCT) characteristics of anti-melanoma differentiation-associated gene 5 (MDA5) antibody positive dermatomyositis-associated interstitial lung disease (anti-MDA5 DM-ILD), and to clarify the underlying mechanisms of the clinical phenomenon. METHODS: Clinical data and HRCT patterns were compared between anti-MDA5 DM-ILD (n = 32) and antisynthetase syndrome-associated ILD (ASS-ILD) (n = 29). RNA sequencing of whole-blood samples from the two groups, and in vitro experiments using human embryonic lung fibroblasts (HELFs) were conducted to explore the potential mechanisms of the clinical findings. RESULTS: The anti-MDA5 DM-ILD subset had a significantly higher incidence of rapidly progressive ILD (RPILD) than ASS-ILD (65.6% vs 37.9%; P = 0.031). The relative percentage of the lung fibrosis HRCT pattern was significantly lower in the anti-MDA5 DM-ILD group, especially the RPILD subgroup (P = 0.013 and 0.003, respectively). RNA sequencing detected the upregulated genes including interferon-induced helicase C domain 1 (encoding MDA5), and a trend towards downregulated expression of TGF-ß signalling components in anti-MDA5 DM-ILD. In vitro culture of HELFs revealed that upregulated expression of MDA5 in HELFs was correlated with the downregulated expression of alpha smooth muscle actin, connective tissue growth factor, collagen I and collagen III by suppressing the TGF-ß signalling pathway. CONCLUSIONS: Anti-MDA5 DM-ILD patients have significantly less lung fibrosis and elevated MDA5 expression. The upregulated expression of MDA5 has relations with the suppression of the pro-fibrotic function of fibroblasts via the TGF-ß signalling pathway, which may partially explain the mechanism of the clinical phenomenon.

Comparison of Three Species of Rhubarb in Inhibiting Vascular Endothelial Injury via Regulation of PI3K/AKT/NF-κB Signaling Pathway.

Background/Aim: Rhubarb, a traditional Chinese medicine derived from three species, is commonly used in the prescriptions for promoting blood circulation and removing blood stasis based on its traditional effects of removing blood stasis and dredging the meridians. It has been reported that rhubarb can protect blood vessels by reducing inflammation and inhibiting vascular endothelial injury (VEI), but the effective components and mechanism of rhubarb inhibiting VEI are still unclear. This study aimed to compare the differences in chemical compositions of the three species of rhubarb and their inhibitory effect on VEI, so as to explain the material basis and select the dominant species to inhibit VEI, and to elucidate the mechanism of rhubarb's inhibitory effect on VEI. Methods: Plant metabolomics was used to compare the chemical components of three species of rhubarb. The efficacy of three species of rhubarb in inhibiting VEI was compared through cell experiments in vitro. At the same time, combined with network pharmacology and molecular docking, the effective components and pathways of rhubarb involved in inhibiting VEI were screened. The mechanism of rhubarb inhibiting VEI was verified by molecular biology. Results: There were significant differences in the distribution of chemical components among the three species of rhubarb. We identified 36 different chemical components in the positive ion mode and 38 different chemical components in the negative ion mode. Subsequently, the results showed significant differences in inhibiting VEI among the three species of rhubarb based on the contents of inflammatory factors (such as IL-1ß, IL-6, and TNF-α), ROS, and NO and confirmed that R. tanguticum had the best inhibitory effect on VEI in the light of the comprehensive efficacy, compared with R. palmatum and R. officinale. Three species of rhubarb alleviated the inflammatory response in LPS-induced EA.hy926 cells by reducing the contents of inflammatory cytokines IL-6, IL-1ß, and TNF-α and decreasing expressions of PI3K, AKT, NF-κB p65, and STAT3 protein in the PI3K/AKT/NF-κB pathway and the inhibition of proteins phosphorylation. In addition, three species of rhubarb could lessen the contents of ROS and NO in EA.hy926 cells induced by LPS. All results indicated that the process of inflammation-induced cellular oxidative stress, which resulted in VEI, was obviously improved by three species of rhubarb. Conclusion: R. tanguticum was more effective among three species of rhubarb, and it had been proved that gallic acid, gallic-acid-O-galloyl-glucoside, procyanidin B-2,3,3'-di-O-gallatein, and other potential components could reduce the contents of inflammatory factors (such as IL-1ß, IL-6, and TNF-α), ROS, and NO by inhibiting the PI3K/AKT/NF-κB signaling pathway and protected the vascular endothelium and the blood vessels by improving the inflammation and oxidative stress reaction.

Image Matching Algorithm Based on the Pattern Recognition Genetic Algorithm.

Image matching is an important topic in image processing. Matching technology plays an important role in and is the basis for image understanding. In order to solve the shortcomings of slow image matching and low matching accuracy, a matching method based on improved genetic algorithm is proposed. The main improvement of the algorithm is the use of self-identifying crossover operators for crossover operations to avoid premature population maturity. According to the characteristics of the image data, new intersection and mutation operators are defined by the new coding method. The sampling method is used to initialize the population method, introduce an evolution strategy, reduce the number of iterations, and effectively reduce the amount of calculation. The experimental results show that the algorithm can guarantee the matching accuracy and that the calculation time is much shorter than that of the original algorithm. In addition, the image matching calculation time per frame of the algorithm is basically unchanged, which is convenient for engineering applications.