A metabolic map and artificial intelligence-aided identification of nasopharyngeal carcinoma via a single-cell Raman platform.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a complex cancer influenced by various factors. This study explores the use of single-cell Raman spectroscopy as a potential diagnostic tool for investigating biomolecular changes associated with NPC carcinogenesis. METHODS: Seven NPC cell lines, one immortalised nasopharyngeal epithelial cell line, six nasopharyngeal mucosa tissues and seven NPC tissue samples were analysed by performing confocal Raman spectroscopic measurements and imaging. The single-cell Raman spectral dataset was used to quantify relevant biomolecules and build machine learning classification models. Metabolomic profiles were investigated using ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). RESULTS: By generating a metabolic map of seven NPC cell lines, we identified an interplay of altered metabolic processes involving nucleic acids, amino acids, lipids and sugars. The results from spatially resolved Raman maps and UPLC-MS/MS metabolomics were consistent, revealing an increase of unsaturated fatty acids in cancer cells, particularly in highly metastatic 5-8F and poorly differentiated CNE2 cells. The classification model achieved a nearly perfect classification when identifying NPC and non-NPC cells with an ROC-AUC of 0.99 and a value of 0.97 when identifying 13 tissue samples. CONCLUSION: This study unveils a complex interplay of metabolic network and highlights the potential roles of unsaturated fatty acids in NPC progression and metastasis. This renders further research to provide deeper insights into NPC pathogenesis, identify new metabolic targets and improve the efficacy of targeted therapies in NPC. Artificial intelligence-aided analysis of single-cell Raman spectra has achieved high accuracies in the classification of both cancer cells and patient tissues, paving the way for a simple, less invasive and accurate diagnostic test.

Astragaloside IV inhibits idiopathic pulmonary fibrosis through activation of autophagy by miR-21-mediated PTEN/PI3K/AKT/mTOR pathway.

As the main active ingredient of Astragalus, Astragaloside IV (AS-IV) can ameliorate pulmonary fibrosis. In this experiment, we studied how AS-IV reduces idiopathic pulmonary fibrosis (IPF). Bleomycin (BLM) or TGF-ß1 was treated in mice or alveolar epithelial cells to mimic IPF in vivo as well as in vitro. ASV-IV alleviated levels of inflammatory cytokines and fibrosis markers in IPF model. Through detection of autophagy-related genes, ASV-IV was observed to induce autophagy in IPF. Besides, ASV-IV inhibited miR-21 expression in IPF models, and overexpression of miR-21 could reverse the protective potential of ASV-IV on IPF. PTEN was targeted by miR-21 and was up-regulated by ASV-IV in IPF models. In addition, levels of inflammatory cytokines and fibrosis markers, autophagy, as well as the PI3K/AKT/mTOR pathway regulated by ASV-IV could be neutralized after treatment with autophagy inhibitors, miR-21 mimics, or si-PTEN. Our study demonstrates that ASV-IV inhibits IPF through activation of autophagy by miR-21-mediated PTEN/PI3K/AKT/mTOR pathway, suggesting that ASV-IV could be acted to be a promising therapeutic method for IPF.

Counteracting mental fatigue for athletes: a systematic review of the interventions.

The deleterious effects of mental fatigue (MF) on athletes have been carefully studied in various sports, such as soccer, badminton, and swimming. Even though many researchers have sought ways to ameliorate the negative impact of MF, there is still a lack of studies that review the interventions used to counteract MF among athletes. This review aims to report the current evidence exploring the effects of interventions on MF and sport-specific performance, including sport-specific motor performance and perceptual-cognitive skills. Web of Science, Scopus, PubMed, and SPORTDicus (EBSCOhost) were combed through to find relevant publications. Additionally, the references and Google Scholar were searched for any grey literature. For the current review, we included only randomized controlled trials that involved athletes, a primary task to induce MF, interventions to counter MF with comparable protocols, and the outcomes of sport-specific motor performance and perceptual-cognitive skill. The selection criteria resulted in the inclusion of 10 articles. The manipulations of autonomous self-control exertion, person-fit, nature exposure, mindfulness, and transactional direct current stimulation showed that positive interventions counteract MF and improve sport-specific performance in different domains, including strength, speed, skill, stamina, and perceptual-cognitive skills. The selected interventions could significantly counteract MF and improve subsequent sport-specific performance. Moreover, self-regulation and attention resources showed the importance of the potential mechanisms behind the relevant interventions.

How to tackle non-specific low back pain among adult patients? A systematic review with a meta-analysis to compare four interventions.

OBJECTIVE: To tackle non-specific low back pain (NSLBP) among patients and find the most effective solution and to quantitatively synthesize the overall effect of motor control training (MCT) compared with Pilates, McKenzie method, and physical therapy (PT) in pain and physical function. METHODS: Randomized controlled trials (RCTs) of four types of intervention (MCT, Pilates, McKenzie method, and PT) for LBP were collected by searching PubMed, Web of Science, EBSCOhost (Cochrane Central Register of Controlled Trials), and Scopus databases from the establishment of the database to September 30, 2023. The risk of bias was evaluated for included studies using the Revised Cochrane Risk of Bias tool for randomized trials (RoB 2.0). Taking pain and physical function in the experimental and control groups as outcome indicators, subgroup analysis was performed according to the intervention method to calculate the standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: A total of 25 RCTs, including 1253 patients, were included. Meta-analysis showed that MCT effectively relieved pain [SMD = -0.65, 95% CI (- 1.00, - 0.29), p < 0.01] and improved physical function [SMD = -0.76, 95% CI (- 1.22, - 0.31), p < 0.01] comparing with other 3 types of intervention. Subgroup analysis suggested that MCT could alleviate pain [SMD = -0.92, 95% CI (- 1.34, - 0.50), p < 0.01] and improve physical function [SMD = -1.15, 95% CI (- 1.72, - 0.57), p < 0.01] compared with PT, but it had no statistical significance compared with Pilates [pain: SMD = 0.13, 95% CI (- 0.56, 0.83), p = 0.71; physical function: SMD = 0.10, 95% CI (- 0.72, 0.91), p = 0.81] and the McKenzie method [pain: SMD = -0.03, 95% CI (- 0.75, 0.68), p = 0.93; physical function: SMD = -0.03, 95% CI (- 1.00, 0.94), p = 0.95]. CONCLUSIONS: MCT can effectively relieve pain and improve physical function in patients with NSLBP. It is more effective compared with PT for LBP, while no differences were detected between MCT and Pilates, as well as McKenzie method. Therefore, MCT, Pilates, and the McKenzie method should be encouraged as exercise interventions for NSLBP rehabilitation.

[Preliminary Study on the Effect of Silencing Nucleostemin Com- bined with Rapamycin on Autophagy and Apoptosis of HL-60 Cells].

OBJECTIVE: To investigate the effects of knocking down nucleostemin ( NS) combined with rapamycin (RAPA) on autophagy and apoptosis in HL-60 cells , and to explore its role in HL-60 cells . METHODS: The expression of NS protein was detected using Western blot , after transfection of HL-60 cells was achieved by the recombinant lentviral vector NS -RNAi-GV248 . Flow cytometry was used to detect changes in cells apoptosis after NS silencing/ rapamycin for 24 , 48 hours , and the expressions of NS , LC3 , p62 , BCL-2 and Bax proteins in cells were detected by Western blot. RESULTS: The expression of NS in HL-60 cells was successfully down-regulated by recombinant lentiviral vector. After treatment with rapamycin for 24 and 48 h , the apoptosis rate of cells in each group increased (P < 0.05) , and the apoptosis was more obvious at 48 hours . Compared with the NS silencing group or rapamycin group , after treated with NS down-regulation combined with rapamycin for 48 hours , the apoptosis of HL-60 cells was significantly increased ( P < 0.05 ) , LC3 -II/LC3 -I ratio was significantly increased ( P < 0.05 ) , p62 protein expression was significantly decreased (P < 0.05) , and BCL-2/Bax ratio was significantly decreased ( P < 0.05) . CONCLUSION: NS down-regulation combined with rapamycin can enhance the apoptosis and autophagy of HL-60 cells , and the induction of apoptosis of HL-60 cells may be related to the expression of BCL-2 and Bax proteins .

Response of soil bacteria on habitat-specialization and abundance gradient to different afforestation types.

Studies involving response of subgroups of soil microorganisms to forest change, especially comparative studies on habitat-specialization and abundance gradient were still lack. In this study, we analyzed the response of soil bacterial diversity and structure to afforestation types and its relationship to environment of Fanggan ecological restoration area under the classification of subgroups by habitat-specialization and abundance gradient based on abundance ratio respectively. The results were: (1) On the habitat-specialization gradient, the variation of OTUs species number and abundance was consistent and positively correlated with habitat-specialization; on the abundance gradient, the variation was opposite and OTUs species number was negatively correlated with abundance gradient; (2) The distribution frequency of each subgroup on both gradients was the highest in broad-leaved forests, but the abundance was the opposite. The distribution frequency of the same stand showed no difference among habitat-specialization subgroups, but the abundant subgroup in broad-leaved forests was the highest among the abundance subgroups; (3) α-diversity was positively correlated with habitat-specialization but negatively with abundance, with the highest mostly in broad-leaved and mixed forests; (4) Community structure among stands on habitat-specialization gradient showed no significant difference, but that of rare subgroup between broad-leaved forests and other stands significantly differed. Plant diversity and vegetation composition correlated stronger with community structure than spatial distance and soil physicochemical properties on both gradients. Our results provided a new perspective for revealing the effects of afforestation types on soil bacteria from the comparison of habitat specialization and abundance gradient.

[Treadmill exercise alleviates neuropathic pain by regulating mitophagy of the anterior cingulate cortex in rats].

This study aimed to investigate the effect of treadmill exercise on neuropathic pain and to determine whether mitophagy of the anterior cingulate cortex (ACC) contributes to exercise-mediated amelioration of neuropathic pain. Chronic constriction injury of the sciatic nerve (CCI) was used to establish a neuropathic pain model in Sprague-Dawley (SD) rats. Von-Frey filaments were used to assess the mechanical paw withdrawal threshold (PWT), and a thermal radiation meter was used to assess the thermal paw withdrawal latency (PWL) in rats. qPCR was used to evaluate the mRNA levels of Pink1, Parkin, Fundc1, and Bnip3. Western blot was used to evaluate the protein levels of PINK1 and PARKIN. To determine the impact of the mitophagy inducer carbonyl cyanide m-chlorophenylhydrazone (CCCP) on pain behaviors in CCI rats, 24 SD rats were randomly divided into CCI drug control group (CCI+Veh group), CCI+CCCP low-dose group (CCI+CCCP0.25), CCI+CCCP medium-dose group (CCI+CCCP2.5), and CCI+CCCP high-dose group (CCI+CCCP5). Pain behaviors were assessed on 0, 1, 3, 5, and 7 days after modeling. To explore whether exercise regulates pain through mitophagy, 24 SD rats were divided into sham, CCI, and CCI+Exercise (CCI+Exe) groups. The rats in the CCI+Exe group underwent 4-week low-moderate treadmill training one week after modeling. The mechanical pain and thermal pain behaviors of the rats in each group were assessed on 0, 7, 14, 21, and 35 days after modeling. Western blot was used to detect the levels of the mitophagy-related proteins PINK1, PARKIN, LC3 II/LC3 I, and P62 in ACC tissues. Transmission electron microscopy was used to observe the ultrastructure of mitochondrial morphology in the ACC. The results showed that: (1) Compared with the sham group, the pain thresholds of the ipsilateral side of the CCI group decreased significantly (P < 0.001). Meanwhile, the mRNA and protein levels of Pink1 were significantly higher, and those of Parkin were lower in the CCI group (P < 0.05). (2) Compared with the CCI+Veh group, each CCCP-dose group showed higher mechanical and thermal pain thresholds, and the levels of PINK1 and LC3 II/LC3 I were elevated significantly (P < 0.05, P < 0.01). (3) The pain thresholds of the CCI+Exe group increased significantly compared with those of the CCI group after treadmill intervention (P < 0.001, P < 0.01). Compared with the CCI group, the protein levels of PINK1 and P62 were decreased (P < 0.001, P < 0.01), and the protein levels of PARKIN and LC3 II/LC3 I were increased in the CCI+Exe group (P < 0.01, P < 0.05). Rod-shaped mitochondria were observed in the ACC of CCI+Exe group, and there were little mitochondrial fragmentation, swelling, or vacuoles. The results suggest that the mitochondrial PINK1/PARKIN autophagy pathway is blocked in the ACC of neuropathic pain model rats. Treadmill exercise could restore mitochondrial homeostasis and relieve neuropathic pain via the PINK1/PARKIN pathway.

Quantitative PCR of string-test collected gastric material: A feasible approach to detect Helicobacter pylori and its resistance against clarithromycin and levofloxacin for susceptibility-guided therapy.

BACKGROUND: As the reduced eradication rate of Helicobacter pylori (H. pylori), we introduced string-test and quantitative PCR (qPCR) for susceptibility-guided therapy innovatively. The practicality of the string test was evaluated. METHODS: It was an open-label, non-randomized, parallel, single-center study, in which subjects tested by 13 C- urea breath test (UBT) and string-qPCR were enrolled. Based on the results of string-qPCR, we calculated clarithromycin and levofloxacin resistance rates and gave 13 C-UBT positive patients 14 days susceptibility-guided bismuth quadruple therapy. In the empirical therapy group, we retrospectively analyzed the treatment results of 13 C-UBT positive patients also treated with bismuth quadruple at Shenzhen Luohu People's Hospital from January 2021 to May 2022. The eradication rate was compared between susceptibility-guided therapy and empirical therapy groups. RESULTS: The diagnosis of H. pylori infection using the string-qPCR had an overall concordance rate of 95.9% with the 13 C-UBT results. Based on the results of string-qPCR, the clarithromycin and levofloxacin resistance rates were 26.1% and 31.8%, respectively. The patients who were given 14 days susceptibility-guided bismuth-based quadruple therapy achieved a high H. pylori eradication rate of 91.8%. Retrospective analysis of patient treatment data from January 2021 to May 2022 available in the hospital database revealed an overall success rate of 82.3% for those who received empirical bismuth-based quadruple therapies, which is marginally significantly lower than that of the string-qPCR susceptibility-guided group (p = 0.084). CONCLUSION: The high treatment success rate of 91.8% indicates that the string-qPCR test is a valuable and feasible approach for clinical practice to help improve H. pylori treatment success rate.

Comparison of the Aroma-Active Compounds and Sensory Characteristics of Different Grades of Light-Flavor Baijiu.

This study comprehensively characterized and compared the aroma differences between four different grades of Fenjiu (FJ, the most representative light-flavor Baijiu). Aroma-active compounds were analyzed by liquid-liquid extraction (LLE) coupled with gas chromatography-olfactometry-mass spectrometry (GC-O-MS). A total of 88 aroma-active compounds were identified, and 70 of them were quantified. The results showed that a majority of aroma compounds in high-grade FJ had higher aroma intensities and concentrations. Among these compounds, there were 28 compounds with odor activity values (OAVs) greater than one in all four wines, which indicated that they might contribute to the characteristic aroma of FJ. Temporal dominance of sensation (TDS) and quantitative descriptive analysis (QDA) were used to characterize the sensory differences. The results suggested that high-grade FJ had a rich, pleasant and lasting retronasal aroma perception and exhibited pleasant orthonasal aroma of floral, fruity, sweet and grassy. Partial least squares regression (PLSR) analysis effectively distinguished four kinds of FJ and revealed associations between the orthonasal aroma attributes and the aroma compounds with OAVs >1. There were 15 compounds with variable importance in projection (VIP) values >1, and they were considered potential aroma markers for quality prediction.

A Real-World Study of Optimal Treatment with Anlotinib First-Line Therapy in Advanced Hepatocellular Carcinoma.

Purpose: To observe the efficacy and safety of anlotinib as a first-line treatment for patients with advanced hepatocellular carcinoma (aHCC) in a real-word environment, explore the optimal treatment regimen for patients with aHCC using anlotinib as a first-line treatment. Patients and Methods: Data from 62 patients with aHCC who received anlotinib single-drug first-line therapy between February 2019 and November 2021. Patients received anlotinib monotherapy, which may be interrupted or discontinued or changed in the event of unacceptable or severe adverse events (AEs) or failure to inhibit tumor progression. The primary endpoint was progression-free survival (PFS) and the secondary endpoints were objective response rate(ORR), disease control rate (DCR), overall survival (OS), and safety. Results: Among the 62 patients, in the best overall response assessment, there were 12 with complete response (CR; 19.4%), 17 with partial response (PR; 27.4%), 25 with stable disease (SD; 40.3%), and 8 with progressive disease (PD; 14.5%). The ORR and DCR were 46.8% and 87.1%, respectively. Among the 11 patients who received tyrosine kinase inhibitors (TKIs) combined with programmed death 1 (PD-1) inhibitors after disease progression, three (27.3%) had CR, one (9.1%) had PR, three (27.3%) had SD, and four (36.4%) had PD. Therefore, the ORR and DCR were 36.4% and 63.6%, respectively. The median PFS for anlotinib monotherapy was 7.37 months (95% confidence interval [CI]: 5.88-8.86) and the median OS did not reach. AEs occurred in 95.2% of patients during anlotinib monotherapy, with the most common being thrombocytopenia (51.6%). The incidence of grade ≥3 AEs was 38.7%. Conclusion: Anlotinib is effective and well-tolerated as a first-line treatment for patients with aHCC. Treatment with TKIs and PD-1 inhibitors after disease progression has also shown preliminary efficacy and safety; therefore, sequential therapy with anlotinib-TKIs and PD-1 inhibitors may be an effective treatment for patients with aHCC.

Research on Expressive Writing in Psychology: A Forty-year Bibliometric Analysis and Visualization of Current Status and Research Trends.

This study offers a systematic review of global academic publications of studies on expressive writing in psychology to date. By using two visualization tools VOSviewer and CiteSpace, we analyzed 1,429 articles on expressive writing from the Web of Science (WoS) Core Collection database. This study might be the first attempt at providing a visualized analysis of the existing expressive writing research. It discusses the results from the following three aspects: (1) the descriptive analysis of general results based on publications, (2) the content analysis based on highly cited articles and keyword analysis, (3) the thematic evolution based on co-word analysis and bursts detection. It is found that the application of expressive writing to minority ethnic groups might be one of the future research interests. The study proposes the necessity of conducting research in the context of positive psychology, argues for a combined use of creative and expressive writing in future studies, and suggests the potential of second/foreign language expressive writing research. The study can be used to enhance researchers' understanding of expressive writing research and provide insights into future research opportunities in this area.

Dysgonomonas mossii Strain Shenzhen WH 0221, a New Member of the Genus Dysgonomonas Isolated from the Blood of a Patient with Diabetic Nephropathy, Exhibits Multiple Antibiotic Resistance.

Herein, we present a new bacterial strain isolated from infected blood of a patient with diabetic nephropathy. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry failed to identify the strain. 16S rRNA gene sequencing showed the highest similarity (>99.5%) with genus Dysgonomonas, but the strain could not be distinguished from Dysgonomonas oryzarvi and Dysgonomonas mossii. Whole genome sequencing, followed by phylogenetic analysis and average nucleotide identity (>95%) analysis, confirmed that the new strain represented Dysgonomonas mossii, leading it to be named Dysgonomonas mossii strain Shenzhen WH 0221. Shenzhen WH 0221 was 3.60 Mb with 37.4% GC content. It was Gram-stain negative, facultatively anaerobic, and grown on Columbia agar supplemented with 5% of sheep blood, exhibiting a smooth surface and pinpoint morphology. The morphological characteristics of this strain include a short rod shape without flagella and a size of 0.45-0.55 × 0.95-1.52 µm observed under transmission electron microscopy. The physiological and biochemical features and major cellular fatty acids (characterized by C14:0 3-OH, C14:0 9-CH3, and C16:0) differed from D. mossii CCUG 43457T and other members of the genus Dysgonomonas. The isolate was found resistant to most cephalosporins, penicillin, norfloxacin, vancomycin, and chloramphenicol, but was susceptible to meropenem, imipenem, tetracycline, clindamycin, and amoxicillin-clavulanic acid. Genes kdpE, ykkD, cmeB, TLA-3, and vanRM found in its genome are probably associated with multiple antibiotic resistance. Lipopolysaccharides, capsules, and cytolysin may also help to illuminate its potential pathogenicity. This is the first report of a case of sepsis caused by Dysgonomonas mossii, and its pathogenic system was analyzed by whole genome sequencing. IMPORTANCE This study identified a new strain, Dysgonomonas mossii strain Shenzhen WH 0221, which has been first reported to cause sepsis isolated from infected blood of a patient with diabetic nephropathy. Physiological and biochemical characterizations, as well as overall fatty acid profile, distinguish Shenzhen WH 0221 from other species of the same genus. However, limited antibiotics were researched for Dysgonomonas mossii. Seventeen antibiotics spanning at least 6 classes were studied, providing a valuable guide to the clinical usage of drugs to treat Dysgonomonas mossii infection. For the first time, we report genome-based functional predictions for Dysgonomonas mossii. Five antibiotic resistance ontologies and more than 200 virulence factors likely underlie the multidrug resistance of Shenzhen WH 0221 and its potential pathogenicity.

Vintage analysis of Chinese Baijiu by GC and 1H NMR combined with multivariable analysis.

Economical-driven counterfeit and inferior aged Chinese Baijiu has caused serious concern of publicity in China. In this study, a total of 167 authentic Chinese Baijiu samples with different vintages including 3 flavor types were carefully collected. Gas chromatography (GC) was used to determine main volatile components and proton nuclear magnetic resonance (1H NMR) spectroscopy was employed to obtain non-targeted fingerprints of Chinese Baijiu samples. Partial least squares regression (PLSR) models, which were confirmed by internal and external validation, were established for effectively identifying actual storage vintage of Chinese Baijiu with various brands, flavor types. Centering (Ctr), pareto scaling (Par), unit variance scaling (UV) data pretreatment methods, principal components (PCs), and three modified variable selection methods were proposed to successfully optimize the vintage model and effectively extract important vintage characteristic factors. This study demonstrated that NMR and GC combined with multivariate statistical analysis are effective tools for validating vintage authenticity of Chinese Baijiu.

Determination and comparison of flavor (retronasal) threshold values of 19 flavor compounds in Baijiu.

Nineteen compounds, including ten esters, six acids, and three alcohols, were characterized and considered as significant tastants and aromas in Baijiu (Chinese Liquor). The flavor (retronasal) threshold values (FTVs) of these 19 compounds were determined by the 10 samples test method in hydroalcoholic solutions (46% v/v in ethanol). The FTVs of the compounds were calculated based on the best estimate threshold method. All the FTVs determined by the professional Chinese Baijiu tasters were lower than those by the nonprofessional tasters. For instance, the detection (2.31 mg/kg) and recognition (11.74 mg/kg) values of ethyl hexanoate determined by the nonprofessional group were higher than the respectively corresponding values 0.44 and 3.80 mg/kg determined by the professional group. All of the odor activity values (OAVs) of ethyl valerate (OAV: 1176.00 to 2321.17), ethyl octanoate (OAV: 6841.20 to 7851.60), and 1-butanol (OAV: 26.78 to 39.72) in Gujinggong Baijiu were more than 10-fold larger than their dose-over-threshold values (DoTs), for which the DoTs of ethyl valerate, ethyl octanoate, and 1-butanol were 92.84 to 183.25, 180.03 to 206.62, 1.18 to 1.75, respectively. On the contrary, the OAVs of ethyl heptanoate (OAV: 3.60 to 5.70) and isoamyl alcohol (OAV: 1.18 to 1.57) were lower than their corresponding DoTs at 152.62 to 241.63 and 12.26 to 16.41. The results demonstrated that it is necessary to consider and compare their DoTs and OAVs simultaneously on evaluating the contribution of flavor compounds in Baijiu. PRACTICAL APPLICATION: Sensory evaluation of threshold values of various flavor compounds could be significantly affected by their existing matrix. Most of the published results of the flavor threshold value of compounds were determined from the matrix such as beer, whiskey, red wine, rather than Chinese Baijiu. The results of this work not only could provide valuable information for flavor studies of Chinese Baijiu but also give useful information for the Baijiu industry to quality control.

Protective effects of liquiritin on UVB-induced skin damage in SD rats.

Overexposure to ultraviolet B (UVB) rays can cause damage to the skin. Liquiritin has a variety of pharmacological effects, such as anti-inflammatory and antioxidant. In the present study, the effect of liquiritin on UVB irradiated rat skin was investigated. Results showed that UVB irradiation caused erythema and wrinkles on the skin surface, as well as thickening and loss of elasticity of the epidermis and a significant increase in the level of ROS in the skin tissue. At the same time, western blot detected an increase in nuclear factor kappa-B (NF-κB) and matrix metalloproteinases (MMPs) and Elisa also detected an increase in pro-inflammatory factors. Therefore, we hypothesized that UVB irradiation-induced damage is associated with inflammation. Interestingly, application of liquiritin to exposed skin of rats reduced the increase in ROS, pro-inflammatory factors, and MMPs caused by UVB irradiation and increased the levels of Sirtuin3 (SIRT3) and Collagen α1. In addition, after intraperitoneal injection of the SIRT3 inhibitor 3-TYP in rats, the protective effect of liquiritin against UVB damage was found to be diminished. These results suggested that promotion of SIRT3 with liquiritin inhibits UVB-induced production of pro-inflammatory mediators, possibly acting through the SIRT3/ROS/NF-κB pathway. In conclusion, this study suggests that liquiritin is an effective drug candidate for the prevention of UVB damage.

Isoliquiritin ameliorates depression by suppressing NLRP3-mediated pyroptosis via miRNA-27a/SYK/NF-κB axis.

BACKGROUND: The NLRP3-mediated pyroptosis, which could be regulated by miRNA-27a, is a key player in the development of depression. Isoliquiritin is a phenolic flavonoid compound that has been demonstrated to suppress NLRP3-mediated pyroptosis. However, it is still unknown whether isoliquiritin could confer antidepressant activity via decreasing NLRP3-mediated pyroptosis by stimulating miRNA-27a. Thus, in the current study, we explored the antidepressant activity of isoliquiritin and its underlying mechanism. METHODS: Expression of miRNA-27a in depressed patients or mice was measured using qRT-PCR. Luciferase reporter assay was performed to illustrate the link between miRNA-27a and SYK. Lipopolysaccharide (LPS) and chronic social defeat stress (CSDS) depression models were established to investigate the antidepressant actions of isoliquiritin. Changes in miRNA-27a/SYK/NF-κB axis and NLRP3-mediated pyroptosis were also examined. The role of miRNA-27a in isoliquiritin-related antidepressant effect was further investigated by using miRNA-27a inhibitors and mimics of miRNA-27a. RESULTS: Our results showed the miRNA-27a expression was downregulated in the serum of depressed patients, and decreased serum and hippocampus expression of miRNA-27a were observed in rodent models of depression. SYK gene expression was significantly reduced by miRNA-27a mimic incubation. Isoliquiritin profoundly attenuated LPS or CSDS-induced depressive symptoms, as well as CSDS-induced anxiety behavior. In the hippocampus, LPS and CSDS decreased miRNA-27a mRNA expression; increased the protein levels of SYK, p-NF-κB, and NLRP3: cleaved Caspase-1, IL-1ß, and GSDMD-N: and elevated the concentration of IL-1ß, IL-6, and TNF-α, which were all restored by isoliquiritin administration. Meanwhile, isoliquiritin upregulated the hippocampal NeuN protein level, improved the survival and morphology of neurons, and decreased pyroptosis-related neuronal cell death. Moreover, isoliquiritin protected primary microglia against LPS and adenosine triphosphate (ATP) elicited NLRP3 inflammasome activation in vitro, evidenced by declined protein levels of p-NF-κB, NLRP3; cleaved Caspase-1, IL-1ß, and GSDMD-N; upregulated miRNA-27a mRNA expression; and decreased the mRNA and protein levels of SYK. Nevertheless, miRNA-27a inhibitors significantly reversed isoliquiritin-generated therapeutic efficacy in CSDS mice and in vitro. Furthermore, the cytoprotective effect of isoliquiritin was similar to that of miRNA-27a mimics in LPS and ATP-treated primary microglia. Taken together, these findings suggest that isoliquiritin possesses potent antidepressant property, which requires miRNA-27a/SYK/NF-κB axis controlled decrease of pyroptosis via NLRP3 cascade.

Risk factors for cancer-associated myositis: A large-scale multicenter cohort study.

AIM: The aim of this study was to identify the risk factors and prognosis of patients with cancer-associated myositis (CAM). METHOD: Four hundred and eighty-seven patients with dermatomyositis (DM), clinical amyopathic dermatomyositis (CADM) and polymyositis (PM) from 3 clinical centers were enrolled retrospectively in this study. Clinical and laboratory data of CAM and non-CAM patients were compared. Logistic regression analysis was used to identify risk factors of CAM. RESULTS: Out of the 487 patients with DM/CADM/PM, 7.0% (34/487) of patients were classified as CAM. Older age (53.91 ± 13.32 vs. 48.76 ± 14.34 years), heliotrope rash (61.8% vs. 41.9%), shawl sign (41.2% vs. 22.1%), V sign (58.8% vs. 38.6%) were observed significantly more commonly in patients with CAM than those without CAM (all P < .05). Fever (17.7% vs. 37.8%), arthralgia/arthritis (23.5% vs. 45.7%), interstitial lung disease (ILD, 38.2% vs 68.9%) were significantly less common in the CAM group than the non-CAM group. Age at onset (odds ratio [OR] 1.036, 95% CI 1.001-1.072, P = .042), shawl sign (OR 2.748, 95% CI 1.107-6.822, P = .029), anti-transition initiation factor (TIF)-1γ antibody (OR 4.012, 95% CI 1.268-12.687, P = .018) were identified as the initial risk factors for the onset of CAM, and ILD was identified as a protective factor for CAM (OR 0.292, 95% CI 0.115-0.739, P = .009). All-cause mortality was significantly higher in CAM patients compared with non-CAM patients (P = .001). CONCLUSION: The mortality of patients with CAM was higher than DM/CADM/PM patients without cancer. Malignancy should be screened in DM/CADM/PM patients especially with risk factors, including older age, shawl sign, anti-TIF-1γ antibody, and lack of ILD.

Identification wild and cultivated licorice by multidimensional analysis.

Licorice is known as a botanical source in medicine and a sweetening agent in food products. Commercial licorice is from the source of wild and cultivated G. uralensis. It was recognized that the material basis of wild and cultivated licorice is different. This study systematically investigated the difference between them by multidimensional analysis technology. The results showed that the content of starch grain, total dietary fibre (TDF), and 11 secondary metabolite components was significantly different in wild and cultivated licorice. principal component analysis (PCA) and orthogonal partial least square (OPLS-DA) analyses showed that the wild and cultivated licorice samples could be clearly separated based on the acquired data of microscopic, macromolecular substance and secondary metabolite analysis. The main markers were starch grain, isoliquiritin apioside, liquirtin apioside and TDF. Additionally, NIR spectroscpy combined with PLS-DA has demonstrated a suitable, fast and nondestructive methodology for authentication of wild and cultivated licorice.

Predictors of Poor Outcome of Anti-MDA5-Associated Rapidly Progressive Interstitial Lung Disease in a Chinese Cohort with Dermatomyositis.

OBJECTIVE: Antimelanoma differentiation-associated protein 5 (anti-MDA5) autoantibody has been reported in dermatomyositis (DM) to be associated with rapidly progressive interstitial lung disease (RP-ILD). Our study is aimed at determining the clinical characteristics and prognostic factors underpinning anti-MDA5-associated RP-ILD. METHODS: Patients with anti-MDA5-associated DM (aMDA5-DM) were identified at the Peking University People's Hospital. The presence of anti-MDA5 antibody was determined by immunoblotting. Kaplan-Meier, chi-square test, univariate, and multivariate data analyses were used. RESULTS: Out of 213 patients with DM and clinically amyopathic dermatomyositis (CADM), 20.7% (44/213) of patients were identified as aMDA5-DM. Amongst the aMDA5-DM patients, 63.6% (28/44) were identified as having anti-MDA5-associated RP-ILD. During the follow-up, 32.1% (9/28) of patients with anti-MDA5-associated RP-ILD died of respiratory failure. We identified older age and periungual erythema as two independent risk factors for RP-ILD mortality. Age ≥ 57 years at disease onset was significantly associated with poor survival (P = 0.02) in patients with anti-MDA5-associated RP-ILD, while patients with periungual erythema had a better survival rate than those without periungual erythema (P < 0.05). CONCLUSIONS: Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates in DM/CADM patients. More effective intervention should be administered to anti-MDA5-associated RP-ILD patients, especially to senior patients and those without periungual erythema.

Aflatoxin B1 Induces Neurotoxicity through Reactive Oxygen Species Generation, DNA Damage, Apoptosis, and S-Phase Cell Cycle Arrest.

Aflatoxin B1 (AFB1) is a mycotoxin widely distributed in a variety of food commodities and exhibits strong toxicity toward multiple tissues and organs. However, little is known about its neurotoxicity and the associated mechanism. In this study, we observed that brain integrity was markedly damaged in mice after intragastric administration of AFB1 (300 µg/kg/day for 30 days). The toxicity of AFB1 on neuronal cells and the underlying mechanisms were then investigated in the neuroblastoma cell line IMR-32. A cell viability assay showed that the IC50 values of AFB1 on IMR-32 cells were 6.18 µg/mL and 5.87 µg/mL after treatment for 24 h and 48 h, respectively. ROS levels in IMR-32 cells increased significantly in a time- and AFB1 concentration-dependent manner, which was associated with the upregulation of NOX2, and downregulation of OXR1, SOD1, and SOD2. Substantial DNA damage associated with the downregulation of PARP1, BRCA2, and RAD51 was also observed. Furthermore, AFB1 significantly induced S-phase arrest, which is associated with the upregulation of CDKN1A, CDKN2C, and CDKN2D. Finally, AFB1 induced apoptosis involving CASP3 and BAX. Taken together, AFB1 manifests a wide range of cytotoxicity on neuronal cells including ROS accumulation, DNA damage, S-phase arrest, and apoptosis-all of which are key factors for understanding the neurotoxicology of AFB1.