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BACKGROUND: COVID-19 infection shows variant symptoms apart from respiratory symptoms, including the orofacial pain. We aim to research the morbidity, characteristics and potential risk factors of orofacial pain associated with COVID-19 pandemic in China from December 2022 to early 2023. METHODS: A cross-sectional survey was conducted in Fujian Province, China. The demographic and characteristic data of the subjects were collected and analysed. RESULTS: A total of 1526 subjects responded to the survey. The morbidity of orofacial pain increased significantly before and after COVID-19 infection. (42.26% vs. 46.52%, P < .001) A total of 217 (14.22%) subjects with orofacial pain before COVID-19 infection reported the phenomenon of "COVID-19 infection with orofacial pain" (CIOP). Univariate and multivariate logistic regression showed that male (OR = 1.761, P < .001) and other symptoms of COVID-19 (OR = 1.494, P < .001) may be the risk factors for the aggravation of CIOP, while the time of first infection (OR = 0.580, P = .004) and preference for drinking tea or coffee (OR = 0.610, P = .003) may be the protective factors for the aggravation of CIOP. While, the subjects who did not concern about the spread of COVID-19 in oral treatment (OR = 0.639, P = .001), female (OR = 0.749, P = .03), education level (OR = 1.687, P < .001) and income level (OR = 1.796, P < .001), higher PSS-10 score (OR = 1.076, P < .001), and more drugs taken for infection (OR = 1.330, P < .001) were more willing to seek medical treatment. CONCLUSION: The morbidity of orofacial pain appears to have increased significantly due to the COVID-19 epidemic; a number of factors can influence the CIOP including gender, infection period, and beverage preference' psychological factors, gender, education and income level can also influence the intent to seek a dentist.
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Potassium-ion batteries (PIBs) are gaining attention among emerging technologies for their cost-effectiveness and the abundance of resources they utilize. Within this context, bismuth oxyhalides (BiOX) have emerged as exceptional candidates for anode materials in PIBs due to their unique structural and superior electrochemical properties. However, challenges such as structural instability and low electronic conductivity remain to be addressed. In this study, a flower-like BiOBr0.5Cl0.5/rGO composite anode material was synthesized, demonstrating outstanding K+ storage performance. The self-hybridized structure enhances ion adsorption and diffusion, which in turn improves charge and discharge efficiency as well as long-term stability. In situ X-ray diffraction (XRD) tests confirmed the gradual release and alloying potassium storage mechanism of Bi metal, which occurs through the intermediate KxBiOBr0.5Cl0.5 phase within the BiOBr0.5Cl0.5 anode. This composite exhibited a high specific capacity of 246.4 mAh/g at 50 A/g and maintained excellent capacity retention after 2400 cycles at 5 A/g. Additionally, in full battery tests, it showed good rate performance and long cycle life, maintaining a discharge specific capacity of 119.6 mAh/g at a high current density of 10 A/g. Comprehensive characterizations revealed insights into the structural, electrochemical, and kinetic properties, advancing high-performance PIBs.
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Design and integration of multiple redox-active organic scaffolds into tailored polymer structures to enhance the specific capacity and cycling life is a long-term research goal. Inspired by nature, we designed and incorporated a 4-electron accepting dicarbonylpyridinium redox motif into linear (DBMP) and cross-linked polymer (TBMP) structures. Benefiting from the suppressed solubility and higher electronic conductivity, the cross-linked TBMP based electrode exhibits improved cycling stability and higher specific capacity than the linear counterpart. After 4000 cycles at 1 A g-1, TBMP can maintain a high capacity of 252 mA h g-1, surpassing the performance of many reported organic cathodes. The structural evolution and reaction kinetics during charge and discharge have been investigated in detail. This study demonstrates that cross-linking is an effective strategy to push the bio-derived carbonylpyridinium materials for high performance LOBs.
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Flavonoids play an important role in forming wine grapes and wine quality characteristics. The flavonoids of three winter red wine grapes, Yeniang No. 2 (YN2), Marselan (Mar), and Guipu No. 6 (GP6), were analyzed by ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QQQ-MS). Furthermore, the flavonoids in GP6 grapevines using two types of training systems, namely, trellis (T) and espaliers (E), were also compared in this study. Overall, 196 flavonoid metabolites, including 96 flavones, 38 flavonols, 19 flavanones, 18 polyphenols, 15 anthocyanins, 7 isoflavones, and 3 proanthocyanidins, were identified. The flavonoid profiles were remarkably different among these three grape varieties, while they did not change much in the GP6 managed on trellis and espaliers. Grape varieties with different genetic backgrounds have their own unique flavonoid profiles. Compared with Mar-T, isoflavones and flavonols presented higher contents in GP6-T and YN2-T, which mainly contain glycitein, genistin, calycosin, kaempferide, isotrifoliin, and ayanin. The anthocyanin content was significantly higher in YN2-T than in the other two varieties. YN2 and GP6-T present a more stable color, with significantly more acetylated diglucosides and methylated anthocyanins in YN2-T and GP6-T than in Mar-T. Notably, GP6 had more varied flavonoids and the better characteristics to its flavonoid profile out of these three varieties, due to it containing a higher number of anthocyanins, flavone, and flavonols and the greatest number of different flavonoid metabolites (DFMs), with higher contents than YN2 and Mar. Compared with the trellis training system, the espaliers training system increased the content of flavonoids detected in GP6 grape berries; however, the composition of flavonoids strictly depends on the grape variety.
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Flavonoïdes , Métabolomique , Vitis , Vin , Vitis/composition chimique , Vitis/métabolisme , Flavonoïdes/analyse , Flavonoïdes/métabolisme , Vin/analyse , Métabolomique/méthodes , Chine , Chromatographie en phase liquide à haute performance , Anthocyanes/analyse , Anthocyanes/métabolisme , MétabolomeRÉSUMÉ
Bamboo shoot is a healthy food rich in dietary fiber (DF). However, its highly insoluble DF and fibrous texture limit its application in industrially processed foods. To achieve industrial processing of bamboo shoot, cellulase was used to improve the physical characteristics of bamboo shoot DF in this study. After enzymatic hydrolysis, the content of soluble DF (SDF) of bamboo shoot increased by 99.28% (from 5.53% to 11.02%) significantly (p < 0.01). At the same time, the effect of enzymatic-modified bamboo SDF (EMBSDF) on streptozotocin-induced type 2 diabetes rats was explored. Results demonstrated that the high dose of EMBSDF (312.8 mg/kg) treated rats showed significant improvements in terms of glucose tolerance and insulin sensitivity (p < 0.01) compared with the diabetes rats. Meantime, it was observed that the levels of glucagon-like peptide-1, adiponectin and interleukin-4 of high dose of EMBSDF compared with diabetes rats were increased (p < 0.01) by 57.79%, 159.13%, and 6.17%, respectively. The tumor necrosis factor-α, C-reactive protein, and leptin levels were decreased (p < 0.01) by 62.89%, 31.53%, and 7.84%, respectively. Furthermore, apparent kidney and pancreas histology improvements were found in high-dose and mid-dose EMBSDF-treated diabetes rats. These results indicated that the modified DF significantly improved diabetes.
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BACKGROUND: Deer oil (DO), a byproduct of deer meat processing, possesses high nutritional value. This study aims to evaluate the protective effects of DO on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice and to explore its potential mechanisms of action. RESULTS: DO was found to inhibit weight loss and colon shortening in colitis mice, significantly reduce disease activity index scores, and notably enhance the levels of tight junction proteins in colon tissues, thus improving intestinal barrier function. ELISA results indicated that DO markedly alleviated the mice's oxidative stress and inflammatory responses. Western blot analysis further demonstrated that DO significantly inhibited the phosphorylation of NF-κB while up-regulating the expression levels of Nrf2 and HO-1 proteins. Additionally, DO increased the abundance of beneficial bacteria such as Odoribacter, Blautia, and Muribaculum, reduced the abundance of harmful bacteria such as Bacteroides, Helicobacter, and Escherichia-Shigella, and promoted the production of short-chain fatty acids. CONCLUSION: Our study provides the first evidence that DO can effectively improve DSS-induced UC in mice. The underlying mechanisms may involve maintaining intestinal barrier function, inhibiting inflammation, alleviating oxidative stress, and modulation of gut microbiota. These findings offer valuable insights for developing DO as an adjunct treatment for UC and as a functional food. © 2024 Society of Chemical Industry.
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Drug resistance poses a high risk to human health. Extensive use of non-antibiotic drugs contributes to antibiotic resistance genes (ARGs) transfer. However, how they affect the spread of broad-host plasmids in complex biological systems remains unknown. This study investigated the effect of metoprolol on the transfer frequency and host range of ARGs in both intrageneric and intergeneric pure culture systems, as well as in anammox microbiome. The results showed that environmental concentrations of metoprolol significantly promoted the intrageneric and intergeneric conjugative transfer. Initially, metoprolol induced excessive oxidative stress, resulting in high cell membrane permeability and bacterial SOS response. Meanwhile, more pili formation increased the adhesion and contact between bacteria, and the abundance of conjugation-related genes also increased significantly. Activation of the electron transport chain provided more ATP for this energy-consuming process. The underlying mechanism was further verified in the complex anammox conjugative system. Metoprolol induced the enrichment of ARGs and mobile genetic elements. The enhanced bacterial interaction and energy generation facilitated the high conjugative transfer frequency of ARGs. In addition, plasmid-borne ARGs tended to transfer to opportunistic pathogens. This work raises public concerns about the health and ecological risks of non-antibiotic drugs.
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Conjugaison génétique , Métoprolol , Plasmides , Plasmides/génétique , Conjugaison génétique/effets des médicaments et des substances chimiques , Multirésistance bactérienne aux médicaments/génétique , Multirésistance bactérienne aux médicaments/effets des médicaments et des substances chimiques , Antagonistes bêta-adrénergiques/pharmacologie , Transfert horizontal de gène , Bactéries/génétique , Bactéries/effets des médicaments et des substances chimiques , Bactéries/métabolisme , Antibactériens/pharmacologie , Gènes MDR/génétique , Microbiote/effets des médicaments et des substances chimiquesRÉSUMÉ
Background and aims: Inflammatory bowel disease (IBD) is a common chronic inflammatory bowel disease characterized by diarrhea and abdominal pain. Recently human metabolites have been found to help explain the underlying biological mechanisms of diseases of the intestinal system, so we aimed to assess the causal relationship between human blood metabolites and susceptibility to IBD subtypes. Methods: We selected a genome-wide association study (GWAS) of 275 metabolites as the exposure factor, and the GWAS dataset of 10 IBD subtypes as the outcome, followed by univariate and multivariate analyses using a two-sample Mendelian randomization study (MR) to study the causal relationship between exposure and outcome, respectively. A series of sensitivity analyses were also performed to ensure the robustness of the results. Results: A total of 107 metabolites were found to be causally associated on univariate analysis after correcting for false discovery rate (FDR), and a total of 9 metabolites were found to be significantly causally associated on subsequent multivariate and sensitivity analyses. In addition we found causal associations between 7 metabolite pathways and 6 IBD subtypes. Conclusion: Our study confirms that blood metabolites and certain metabolic pathways are causally associated with the development of IBD subtypes and their parenteral manifestations. The exploration of the mechanisms of novel blood metabolites on IBD may provide new therapeutic ideas for IBD patients.
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Rectocolite hémorragique , Maladie de Crohn , Étude d'association pangénomique , Humains , Rectocolite hémorragique/sang , Rectocolite hémorragique/métabolisme , Maladie de Crohn/sang , Maladie de Crohn/métabolisme , Analyse de randomisation mendélienne , Femelle , Mâle , Prédisposition aux maladies , Marqueurs biologiques/sang , Adulte , Métabolome , Prédisposition génétique à une maladieRÉSUMÉ
The antioxidant activities of lycopene (LY), lutein (LU), chlorogenic acid (CA), and delphinidin (DP) were tested in vitro on H9c2 cell-based models. Some indicators, such as the generation of reactive oxygen (ROS), the quantification of cell antioxidant activity (CAA), and the expressions of SOD, GSH-Px, and CAT, were calculated to examine their antioxidant interactions. From our results, the phytochemical mixtures (M1: CA-LU: F3/10, M2: DP-CA: F7/10, M3: DP-LY: F5/10) displayed strong synergistic effects based on the generation of ROS and the quantification of CAA. However, great antagonistic bioactivities were seen in the combinations of LY-LU: F5/10 (M4), CA-LU: F9/10 (M5), and DP-LY: F7/10 (M6). Western blotting analysis indicated that the possible mechanism underlying the synergistic antioxidant interactions among phytochemical combinations was to enhance the accumulation of Nrf2 in the nucleus and the expression of its downstream antioxidant enzymes, HO-1 and GCLC. The combinations (M1-M3 groups) showed significant protection against the loss of mitochondrial membrane potential than individual groups to avoid excessive ROS production. The M4-M6 groups exerted antagonistic protective effects compared with the individual groups. In addition, lutein and lycopene absorption was improved more because of the presence of chlorogenic acid and delphinidin in the M1 and M3 groups, respectively. However, delphinidin significantly reduced the cellular uptake of lycopene in the M6 group. It appeared that antioxidant interactions of phytochemical combinations may contribute to the restoration of cellular redox homeostasis and lead to an improvement in diet quality and collocation.
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Nonenzymatic glycosylation of proteins can generate advanced glycosylation end products, which are closely associated with the pathogenesis of certain chronic physiological diseases and aging. In this study, we characterized the covalent binding of cyanidin-3-glucoside (C3G) to bovine serum albumin (BSA) and investigated the mechanism by which this covalent binding inhibits the nonenzymatic glycosylation of BSA. The results indicated that the covalent interaction between C3G and BSA stabilized the protein's secondary structure. Through liquid chromatography-electrospray ionization tandem mass spectrometry analysis, we identified the covalent binding sites of C3G on BSA as lysine, arginine, asparagine, glutamine, and cysteine residues. This covalent interaction significantly suppressed the nonenzymatic glycosylation of BSA, consequently reducing the formation of nonenzymatic glycosylation products. C3G competitively binds to nonenzymatic glycosylation sites (e.g., lysine and arginine) on BSA, thereby impeding the glycosylation process and preventing the misfolding and structural alterations of BSA induced by fructose. Furthermore, the covalent attachment of C3G to BSA preserves the secondary structure of BSA and hinders subsequent nonenzymatic glycosylation events.
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Anthocyanes , Glucosides , Sérumalbumine bovine , Glycosylation , Sérumalbumine bovine/composition chimique , Sérumalbumine bovine/métabolisme , Anthocyanes/composition chimique , Anthocyanes/métabolisme , Glucosides/métabolisme , Glucosides/composition chimique , Animaux , Sites de fixation , Bovins , Structure secondaire des protéines , Produits terminaux de glycation avancée/composition chimique , Produits terminaux de glycation avancée/métabolisme , Liaison aux protéines , Spectrométrie de masse en tandem , Spectrométrie de masse ESIRÉSUMÉ
Recent studies increasingly suggest a connection between lipids and idiopathic pulmonary fibrosis (IPF). This study was aimed at exploring potential lipid-related biomarkers for IPF and uncovering the mechanisms underlying pulmonary fibrosis. IPF-related datasets were retrieved from the GEO database, and the ComBat algorithm was used to merge multiple datasets and eliminate batch effects. Weighted gene co-expression network analysis (WGCNA) was utilized to identify modules and genes associated with IPF. Potential hub genes were determined by intersecting these genes with lipid-related genes from the GeneCards database. A machine learning-based integrative approach was developed to construct diagnostic and prognostic signatures, which were validated across several datasets. Additionally, single-cell sequencing data was used to validate the expression differences of core IPF-related genes across various cell types. The effect of ABHD5 on fibroblasts was assessed using the cell counting kit-8, 5-ethynyl-2'-deoxyuridine, and cell scratch assays. The expression levels of fibrotic factors were measured using real-time quantitative polymerase chain reaction and western blot analysis. WGCNA identified a red module potentially related to IPF, and the intersection with lipid-related genes yielded 51 hub genes. These genes were used to build diagnostic and prognostic models that demonstrated robust validation capabilities across multiple datasets. Single-cell sequencing analysis revealed low expression of ABHD5 in the lung tissues of IPF patients, with a higher proportion of fibroblasts exhibiting low ABHD5 expression. Cell experiments showed that under the influence of TGF-ß1, knockdown of ABHD5 slightly promoted fibroblast proliferation. Additionally, fibroblasts with low ABHD5 expression exhibited enhanced migratory capabilities and secreted more fibrotic factors. Lipid-related diagnostic and prognostic models for IPF were developed, and ABHD5 may serve as a potential biomarker. Low ABHD5 expression could potentially accelerate the progression of pulmonary fibrosis.
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Remote ischemic post-conditioning (RIPostC) can reduce cerebral ischemia reperfusion injury (IRI) by inducing endogenous protective effects, the distal limb ischemia post-treatment and in situ ischemia post-treatment were classified according to the site of intervention. And in the process of clinical application distal limb ischemia post-treatment is more widely used and more conducive to clinical translation. Therefore, in this paper, we review the mechanism of action and clinical application of RIPostC in cerebral ischemia, hoping to provide reference help for future experimental directions and clinical translation.
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Postconditionnement ischémique , Accident vasculaire cérébral ischémique , Humains , Postconditionnement ischémique/méthodes , Accident vasculaire cérébral ischémique/thérapie , Lésion d'ischémie-reperfusion/thérapie , Encéphalopathie ischémique/thérapie , AnimauxRÉSUMÉ
Multiple myeloma, which is a clonal plasma cell tumor, derives from a postmitotic lymphoid B-cell lineage and remains untreatable. Group XVI phospholipase A2 (PLA2G16) can either be a tumor suppressor or an oncogene in different types of cancer. This study was intended to explore the role of PLA2G16 in multiple myeloma and to reveal the reaction mechanism. The mRNA and protein expressions of PLA2G16 in human bone marrow stromal cell line HS-5 and multiple myeloma cells were assessed using reverse transcription-quantitative PCR and western blot. The transfection efficacy of sh-PLA2G16 and oe-YAP was examined using reverse transcription-quantitative PCR and western blot. Through cell counting kit-8 assay and 5-ethynyl-2'- deoxyuridine staining, multiple myeloma cell viability and proliferation were detected. Flow cytometry was used to measure cell apoptosis and cell cycle distribution. Oxygen consumption rate, the activities of mitochondrial respiratory chain complexes I-V, and the activity of caspase-3 were estimated with Seahorse XF24 analyzer, oxidative phosphorylation activity assay kit, and caspase-3 assay kit, respectively. Lactate production and glucose consumption were evaluated usingcorresponding assay kits. Western blot was employed to meaure proteins associated with cell cycle, glycolysis, pentose phosphate pathway as well as Hippo/YAP signaling pathway. In this study, PLA2G16 expression was greatly increased in multiple myeloma cells and PLA2G16 silence inhibited cell proliferation, promoted cell apoptosis, facilitated cell cycle arrest, and suppressed the reprogramming of glucose metabolism in multiple myeloma. It was also identified that PLA2G16 depletion inhibited the Hippo/YAP signaling pathway. Further experiments revealed that the overexpression of YAP partially reversed the inhibitory effects of PLA2G16 silence on multiple myeloma cell malignant development and the reprogramming of glucose metabolism. Collectively, PLA2G16 silence impeded multiple myeloma progression and inhibited glucose metabolism reprogramming by blocking the Hippo/YAP signaling pathway.
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Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide, but the underlying molecular mechanisms remain largely unclear. The transcription factor (TF) specificity protein 1 (SP1) plays a crucial role in the development of various cancers, including LUAD. Recent studies have indicated that master TFs may form phase-separated macromolecular condensates to promote super-enhancer (SE) assembly and oncogene expression. In this study, we demonstrated that SP1 undergoes phase separation and that its zinc finger 3 in the DNA-binding domain is essential for this process. Through Cleavage Under Targets & Release Using Nuclease (CUT&RUN) using antibodies against SP1 and H3K27ac, we found a significant correlation between SP1 enrichment and SE elements, identified the regulator of the G protein signaling 20 (RGS20) gene as the most likely target regulated by SP1 through SE mechanisms, and verified this finding using different approaches. The oncogenic activity of SP1 relies on its phase separation ability and RGS20 gene activation, which can be abolished by glycogen synthase kinase J4 (GSK-J4), a demethylase inhibitor. Together, our findings provide evidence that SP1 regulates its target oncogene expression through phase separation and SE mechanisms, thereby promoting LUAD cell progression. This study also revealed an innovative target for LUAD therapies through intervening in SP1-mediated SE formation.
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Adénocarcinome pulmonaire , Régulation de l'expression des gènes tumoraux , Tumeurs du poumon , Protéines RGS , Facteur de transcription Sp1 , Facteur de transcription Sp1/métabolisme , Facteur de transcription Sp1/génétique , Humains , Adénocarcinome pulmonaire/métabolisme , Adénocarcinome pulmonaire/anatomopathologie , Adénocarcinome pulmonaire/génétique , Tumeurs du poumon/métabolisme , Tumeurs du poumon/anatomopathologie , Tumeurs du poumon/génétique , Protéines RGS/métabolisme , Protéines RGS/génétique , Lignée cellulaire tumorale , Animaux , Éléments activateurs (génétique) , Évolution de la maladie , Souris ,RÉSUMÉ
Purpose: Diffuse large B-cell lymphoma (DLBCL) is a prevalent malignant condition with a dismal prognosis. LncRNA PGM5 antisense RNA 1 (PGM5-AS1) appears to be intricately involved in the progression of DLBCL, yet the modulatory mechanism remains unclear. The purpose of this study was to explore the expression of lncRNA PGM5-AS1 in DLBCL and its effect on the disease progression of DLBCL, as well as to explore its mechanisms. Patients and Methods: A total of 35 patients were included in the study. The expression levels of PGM5-AS1 and miR-503-5p in DLBCL tumor tissues and cell lines were detected by RT-qPCR. Cell proliferation was assessed using CCK8. Apoptosis rate was determined by flow cytometry. Cell invasion was examined by transwell assays. The specific interaction between PGM5-AS1 and miR-503-5p was verified through dual luciferase reporter gene assays. The immune related factors were detected by ELASA kits. The CD8+ T cells cytotoxicity was evaluated by LDH cytotoxicity kit. Results: In DLBCL tumor tissues and cells, upregulated PGM5-AS1 expression, downregulated miR-503-5p expression, and elevated PD-L1 expression were observed. PGM5-AS1 functioned as a regulator in controlling DLBCL cell proliferation, apoptosis, and invasion by downregulating miR-503-5p expression. When CD8+ T cells were co-cultured with cells transfected with si-PGM5-AS1, the secretion of immunoregulatory factors increased, and the cytotoxicity of CD8+ T cells increased. These effects were mitigated by miR-503-5p inhibitors. Conclusion: PGM5-AS1 accelerated DLBCL development and facilitated tumor immune escape through the miR-503-5p. Our discoveries offered an insight into lncRNA PGM5-AS1 serving as a prospective therapeutic target for DLBCL.
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Neurosyphilis is a central nervous system infection caused by Treponema pallidum that imitates various neurological and mental disorders. Therefore, patients with this disease are prone to misdiagnoses. Here, we report a case of neurosyphilis with a psychotic disorder as the main manifestation. A young girl exhibited mental and behavioural abnormalities after a heartbreak, which manifested as alternating low mood, emotional irritability, and a lack of interest in social relations, followed by memory loss. The cerebrospinal fluid protein - Treponema pallidum particle agglutination test was positive, the toluidine red unheated serum test titre was 1:4, the white blood cell count was 5 × 10^6/L, the cerebrospinal fluid protein level was 0.97 g/L, and the brain CT was abnormal. After admission, the possibility of neurosyphilis was considered and the patient received intravenous penicillin G treatment. The patient's clinical symptom ms improved. This case emphasises that doctors should maintain clinical suspicion of Treponema pallidum infection in adolescent patients with mental abnormalities.
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Metals are essential for human health and play a crucial role in numerous biological processes and pathways. Gaining a deeper insight into these biological events will facilitate novel strategies for disease prevention, early detection, and personalized treatment. In recent years, there has been significant progress in the development of metal-detection based techniques from single cell metallome and proteome profiling to multiplex imaging, which greatly enhance our comprehension of the intricate roles played by metals in complex biological systems. This perspective summarizes the recent progress in advanced metal-detection based techniques and highlights successful applications in elucidating the roles of metals in biology and medicine. Technologies including machine learning that couple with single-cell analysis such as mass cytometry and their application in metallobiology, cancer biology and immunology are also emphasized. Finally, we provide insights into future prospects and challenges involved in metal-detection based techniques, with the aim of inspiring further methodological advancements and applications that are accessible to chemists, biologists, and clinicians.
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Lung cancer persistently leads as the primary cause of morbidity and mortality among malignancies. A notable increase in the prevalence of lung adenocarcinoma has become evident in recent years. Although targeted therapies have shown in treating certain subsets of non-small cell lung cancers (NSCLC), a significant proportion of patients still face suboptimal therapeutic outcomes. Neuregulin-1 (NRG1), a critical member of the NRG gene family, initially drew interest due to its distribution within the nascent ventricular endocardium, showcasing an exclusive presence in the endocardium and myocardial microvessels. Recent research has highlighted NRG1's pivotal role in the genesis and progression across a spectrum of tumors, influencing molecular perturbations across various tumor-associated signaling pathways. This review provides a concise overview of NRG1, including its expression patterns, configuration, and fusion partners. Additionally, we explore the unique features and potential therapeutic strategies for NRG1 fusion-positive occurrences within the context of NSCLC.
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Due to the similarity and diversity among kinases, small molecule kinase inhibitors (SMKIs) often display multi-target effects or selectivity, which have a strong correlation with the efficacy and safety of these inhibitors. However, due to the limited number of well-known popular databases and their restricted data mining capabilities, along with the significant scarcity of databases focusing on the pharmacological similarity and diversity of SMIKIs, researchers find it challenging to quickly access relevant information. The KLIFS database is representative of specialized application databases in the field, focusing on kinase structure and co-crystallised kinase-ligand interactions, whereas the KLSD database in this paper emphasizes the analysis of SMKIs among all reported kinase targets. To solve the current problem of the lack of professional application databases in kinase research and to provide centralized, standardized, reliable and efficient data resources for kinase researchers, this paper proposes a research program based on the ChEMBL database. It focuses on kinase ligands activities comparisons. This scheme extracts kinase data and standardizes and normalizes them, then performs kinase target difference analysis to achieve kinase activity threshold judgement. It then constructs a specialized and personalized kinase database platform, adopts the front-end and back-end separation technology of SpringBoot architecture, constructs an extensible WEB application, handles the storage, retrieval and analysis of the data, ultimately realizing data visualization and interaction. This study aims to develop a kinase database platform to collect, organize, and provide standardized data related to kinases. By offering essential resources and tools, it supports kinase research and drug development, thereby advancing scientific research and innovation in kinase-related fields. It is freely accessible at: http://ai.njucm.edu.cn:8080.
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The COVID-19 pandemic caused by SARS-CoV-2 resulted in a global public health crisis. In addition to vaccines, the development of effective therapy is highly desirable. Targeting a protein that plays a critical role in virus replication may allow pan-spectrum antiviral drugs to be developed. Among SARS-CoV-2 proteins, helicase (i.e., non-structural protein 13) is considered as a promising antiviral drug target due to its highly conserved sequence, unique structure and function. Herein, we demonstrate SARS-CoV-2 helicase as a target of bismuth-based antivirals in virus-infected mammalian cells by a metal-tagged antibody approach. To search for more potent bismuth-based antivirals, we further screened a panel of bismuth compounds towards inhibition of ATPase and DNA unwinding activity of nsp13 and identified a highly potent bismuth compound Bi(5-aminotropolonate)3, namely Bi(Tro-NH2)3 with an IC50 of 30 nM for ATPase. We show that bismuth-based compounds inhibited nsp13 unwinding activity via disrupting the binding of ATP and the DNA substrate to viral helicase. Binding of Bi(iii) to nsp13 also abolished the interaction between nsp12 and nsp13 as evidenced by immunofluorescence and co-immunoprecipitation assays. Finally, we validate our in vitro data in SARS-CoV-2 infected mammalian cells. Notably, Bi(6-TG)3 exhibited an EC50 of 1.18 ± 0.09 µM with a selective index of 847 in VeroE6-TMPRSS2 infected cells. This study highlights the important role of helicase for the development of more effective antiviral drugs to combat SARS-CoV-2 infection.