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BACKGROUND: Oxaliplatin resistance usually leads to therapeutic failure and poor prognosis in colorectal cancer (CRC), while the underlying mechanisms are not yet fully understood. Metabolic reprogramming is strongly linked to drug resistance, however, the role and mechanism of metabolic reprogramming in oxaliplatin resistance remain unclear. Here, we aim to explore the functions and mechanisms of purine metabolism on the oxaliplatin-induced apoptosis of CRC. METHODS: An oxaliplatin-resistant CRC cell line was generated, and untargeted metabolomics analysis was conducted. The inosine 5'-monophosphate dehydrogenase type II (IMPDH2) expression in CRC cell lines was determined by quantitative real-time polymerase chain reaction (qPCR) and western blotting analysis. The effects of IMPDH2 overexpression, knockdown and pharmacological inhibition on oxaliplatin resistance in CRC were assessed by flow cytometry analysis of cell apoptosis in vivo and in vitro. RESULTS: Metabolic analysis revealed that the levels of purine metabolites, especially guanosine monophosphate (GMP), were markedly elevated in oxaliplatin-resistant CRC cells. The accumulation of purine metabolites mainly arose from the upregulation of IMPDH2 expression. Gene set enrichment analysis (GSEA) indicated high IMPDH2 expression in CRC correlates with PURINE_METABOLISM and MULTIPLE-DRUG-RESISTANCE pathways. CRC cells with higher IMPDH2 expression were more resistant to oxaliplatin-induced apoptosis. Overexpression of IMPDH2 in CRC cells resulted in reduced cell death upon treatment with oxaliplatin, whereas knockdown of IMPDH2 led to increased sensitivity to oxaliplatin through influencing the activation of the Caspase 7/8/9 and PARP1 proteins on cell apoptosis. Targeted inhibition of IMPDH2 by mycophenolic acid (MPA) or mycophenolate mofetil (MMF) enhanced cell apoptosis in vitro and decreased in vivo tumour burden when combined with oxaliplatin treatment. Mechanistically, the Wnt/ß-catenin signalling was hyperactivated in oxaliplatin-resistant CRC cells, and a reciprocal positive regulatory mechanism existed between Wnt/ß-catenin and IMPDH2. Blocking the Wnt/ß-catenin pathway could resensitize resistant cells to oxaliplatin, which could be restored by the addition of GMP. CONCLUSIONS: IMPDH2 is a predictive biomarker and therapeutic target for oxaliplatin resistance in CRC.
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Neoplasias Colorretais , beta Catenina , Humanos , Apoptose , beta Catenina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , IMP Desidrogenase/genética , IMP Desidrogenase/metabolismo , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Oxirredutases/genética , Oxirredutases/metabolismo , Via de Sinalização WntRESUMO
Human papillomavirus (HPV) infection can lead to HPV-related cancer in men, including the anus, penile, and oropharyngeal cancers and precancerous lesions. This study retrospectively investigated HPV prevalence and genotype distribution in Liaocheng men between 2016 and 2022. The total HPV positive rate was 64.87% (2388/3681, 95% confidence interval [CI]: 63.32%-66.40%), where high risk (HR)-HPV and low risk (LR)-HPV accounted for 42.49% (1564/3681, 95% CI: 40.90%-44.09%) and 69.71% (2566/3681, 95% CI: 68.20%-71.17%), respectively. The mixed HPV infection rate of two and more genotypes was 35.72%. The infection rate of HR-HPV increased with the number of positive cases annually from 2016 (16.91%) to 2022 (46.59%). The most common HR-HPV genotypes were HPV16 (11.60%), HPV52 (6.95%), and HPV59 (6.28%), whereas the least common HR-HPV was HPV26. The most common LR-HPV genotypes were HPV6 (56.99%), HPV11 (23.79%), and HPV43 (6.37%). The 9 v HPV vaccine preventable for LR-HPV and HR-HPV accounted for 80.78% and 30.40%, respectively, in this study. Most HPV-positive patients aged 1-86 were in the 30-39 age group. This study confirmed that HPV prevalence in Liaocheng men was common and diverse. HPV16, HPV52, and HPV59 are widely distributed in Liaocheng men, and the male HR-HPV infection rate remained high in this region. Regarding public health and cancer prevention, it is recommended and effective to include the HPV vaccination in the national vaccination program for men.
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Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Masculino , Adulto , Prevalência , Estudos Retrospectivos , Papillomavirus Humano 18 , Papillomaviridae/genética , Papillomavirus Humano 16/genética , GenótipoRESUMO
Lithium-sulfur batteries have garnered significant attention as a promising next-generation battery technology due to their potential for high energy density. However, their practical application is hampered by slow reaction kinetics and the shuttle effect of lithium polysulfide intermediates. In this context, the authors introduce a pioneering solution in the form of a novel porous carbon nanostructure modified with samarium oxide, denoted as Sm2O3/KB. The material has a highly polar surface, allowing lithium polysulfide to be chemisorbed efficiently. The unsaturated sites provided by the oxygen vacancies of Sm2O3 promote Li2S nucleation, lowering the reaction energy barrier and accelerating Li2S dissolution. The porous structure of Ketjen Black provides a highly conductive channel for electron transport and effectively traps polysulfides. Meanwhile, the batteries with Sm2O3/KB/PP spacers exhibited remarkable electrochemical performances, including a low-capacity decay rate of only 0.046 % for 1000 cycles at 2â C and an excellent multiplicative performance of 624â mAh g-1 at 3â C. This work opens up a new avenue for the potential use of rare-earth-based materials in lithium-sulfur batteries.
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As the most abundant d-amino acid (DAA) in the ocean, d-alanine (d-Ala) is a key component of peptidoglycan in the bacterial cell wall. However, the underlying mechanisms of bacterial metabolization of d-Ala through the microbial food web remain largely unknown. In this study, the metabolism of d-Ala by marine bacterium Pseudoalteromonas sp. strain CF6-2 was investigated. Based on genomic, transcriptional, and biochemical analyses combined with gene knockout, d-Ala aminotransferase was found to be indispensable for the catabolism of d-Ala in strain CF6-2. Investigation on other marine bacteria also showed that d-Ala aminotransferase gene is a reliable indicator for their ability to utilize d-Ala. Bioinformatic investigation revealed that d-Ala aminotransferase sequences are prevalent in genomes of marine bacteria and metagenomes, especially in seawater samples, and Gammaproteobacteria represents the predominant group containing d-Ala aminotransferase. Thus, Gammaproteobacteria is likely the dominant group to utilize d-Ala via d-Ala aminotransferase to drive the recycling and mineralization of d-Ala in the ocean. IMPORTANCE As the most abundant d-amino acid in the ocean, d-Ala is a component of the marine DON (dissolved organic nitrogen) pool. However, the underlying mechanism of bacterial metabolization of d-Ala to drive the recycling and mineralization of d-Ala in the ocean is still largely unknown. The results in this study showed that d-Ala aminotransferase is specific and indispensable for d-Ala catabolism in marine bacteria and that marine bacteria containing d-Ala aminotransferase genes are predominantly Gammaproteobacteria widely distributed in global oceans. This study reveals marine d-Ala-utilizing bacteria and the mechanism of their metabolization of d-Ala. The results shed light on the mechanisms of recycling and mineralization of d-Ala driven by bacteria in the ocean, which are helpful in understanding oceanic microbial-mediated nitrogen cycle.
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Pseudoalteromonas , Alanina/metabolismo , Pseudoalteromonas/genética , Pseudoalteromonas/metabolismo , Água do Mar/microbiologia , Transaminases/genéticaRESUMO
Current cancer treatment regimens such as chemotherapy and traditional chemical drugs have adverse side effects including the appearance of drug-resistant tumor cells. For these reasons, it is imperative to find novel therapeutic agents that overcome these factors. To this end, we explored a cationic antimicrobial peptide derived from Litopenaeus vannamei hemocyanin (designated LvHemB1) that induces cancer cell death, but sparing normal cells. LvHemB1 inhibits the proliferation of human cervical (HeLa), esophageal (EC109), hepatocellular (HepG2), and bladder (EJ) cancer cell lines, but had no significant effect on normal liver cell lines (T-antigen-immortalized human liver epithelial (THLE-3) cells). In addition to its antiproliferative effects, LvHemB1 induced apoptosis, by permeating cells and targeting mitochondrial voltage-dependent anion channel 1 (VDAC1). Colocalization studies revealed the localization of LvHemB1 in mitochondria, while molecular docking and pull-down analyses confirmed LvHemB1-VDAC1 interaction. Moreover, LvHemB1 causes loss in mitochondrial membrane potential and increases levels of reactive oxygen species (ROS) and apoptotic proteins (caspase-9, caspase-3, and Bax (Bcl-2-associated X)), which results in mitochondrial-mediated apoptosis. Thus, peptide LvHemB1 has the potential of being used as an anticancer agent due to its antiproliferation effect and targeting to VDAC1 to cause mitochondrial dysfunction in cancer cells, as well as its ability to induce apoptosis by increasing ROS levels, and the expression of proapoptotic proteins.
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Neoplasias , Canal de Ânion 1 Dependente de Voltagem , Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Antimicrobianos , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Hemocianinas/metabolismo , Hemocianinas/farmacologia , Humanos , Potencial da Membrana Mitocondrial , Mitocôndrias/metabolismo , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Canal de Ânion 1 Dependente de Voltagem/química , Canal de Ânion 1 Dependente de Voltagem/metabolismoRESUMO
Graphene oxide (GO) is an excellent chemical tunable optical platform for imaging and sensing. The photoluminescence (PL) quantum yield of GO is relatively low, which limited the application of the intrinsic and tunable fluorescence from GO. Here, we report the first case of metal-enhanced fluorescence (MEF) of GO. A significant enhancement (~10-fold) in fluorescence intensity is observed from GO on the Ag substrate as compared to that on the glass. FL, Raman, and SEM images are used to investigate the MEF behavior and are coincident with each other. The influence of the metal particle size of Ag substrate is investigated. The fluorescence is also found to be responsive when adding different metal ions into GO solution. GO contacting directly with metal substrate exhibits strong MEF without quenching, which makes it possible to use GO sheets for three-dimension optical imaging and sensing.
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Grafite , Fluorescência , Metais , Tamanho da PartículaRESUMO
Colorectal cancer (CRC) is the third most malignant tumour worldwide, with high mortality and recurrence. Chemoresistance is one of the main factors leading to metastasis and poor prognosis in advanced CRC patients. By analysing the Gene Expression Omnibus data set, we found higher hexokinase 2 (HK2) expression levels in patients with metastatic CRC than in those with primary CRC. Moreover, we observed higher enrichment in oxaliplatin resistance-related gene sets in metastatic CRC than in primary CRC. However, the underlying relationship has not yet been elucidated. In our study, HK2 expression was significantly elevated in CRC patients. Gene set enrichment analysis (GSEA) revealed multi-drug resistance and epithelial-mesenchymal transition (EMT) pathways related to high HK2 expression. Our results showed that knockdown of HK2 significantly inhibited vimentin and Twist1 expression and promoted TJP1 and E-cadherin expression in CRC cells. Additionally, transcriptional and enzymatic inhibition of HK2 by 3-bromopyruvate (3-bp) impaired oxaliplatin resistance in vitro and in vivo. Mechanistically, HK2 interacts with and stabilized Twist1 by preventing its ubiquitin-mediated degradation, which is related to oxaliplatin resistance, in CRC cells. Overexpression of Twist1 reduced the apoptosis rate by HK2 knockdown in CRC cells. Collectively, we discovered that HK2 is a crucial regulator that mediates oxaliplatin resistance through Twist1. These findings identify HK2 and Twist1 as promising drug targets for CRC chemoresistance.
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Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Hexoquinase/metabolismo , Proteínas Nucleares/metabolismo , Oxaliplatina/farmacologia , Proteína 1 Relacionada a Twist/metabolismo , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Endogâmicos BALB CRESUMO
PURPOSE: This study aimed to investigate whether genetic polymorphisms in TGFB1 contribute to breast cancer (BC) susceptibility, and explore the mechanism of action. METHODS: A total of 7 tagging SNPs (tSNPs) were genotyped in 1161 BC cases and 1337 age-matched controls among Chinese Han population. Bioinformatics analysis was used to predict functional SNP closely linked to tSNPs. Luciferase gene reporter assay was performed to determine the effect of genetic variants on promoter activity. DNA pull-down assay and mass spectrometry were used to identify the differentially binding proteins to genetic variants. RESULTS: Genotyping analysis showed that rs1800469 (C>T) in the 5' regulatory region of TGFB1 was associated with reduced BC risk. Bioinformatics analysis predicted that rs11466313 (-2389_-2391 Del/AGG) in the 5' regulatory region of TGFB1, was closely linked to tSNP rs1800469 and could be functional. The genotyping of rs11466313 by PCR-SSCP showed that rs11466313 also conferred decreased BC risk. Luciferase assays demonstrated that rs11466313 minor allele reduced over ninefold of promoter activity compared with its major allele (p < 0.001). DNA pull-down assay and mass spectrometry revealed that rs11466313 minor allele lost the binding ability with FAM98B and HSP90B. Knocking down FAM98B but not HSP90B, the enhanced promoter activity driven by TGFB1 rs11466313 major allele was attenuated. CONCLUSIONS: This study elucidates the impact of functional polymorphism rs11466313 in the regulatory region of TGFB1 on breast cancer susceptibility and gene expression, and could be helpful for future research to determine the value of this TGFB1 variant in the clinical setting.
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Neoplasias da Mama , Alelos , Neoplasias da Mama/genética , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Fator de Crescimento Transformador beta1/genéticaRESUMO
BACKGROUND: Hematopoietic stem cell transplantation (HSCT) has become the standard treatment for many diseases, but it is an intense and distinctive experience for patients. HSCT-related mortality is present throughout the whole process of transplantation, from pretransplantation to recovery. Long-term rehabilitation and the uncertain risk of death evoke feelings of vulnerability, helplessness, and intense fear. Zimmermann et al. proposed that spiritual well-being is an important dimension of quality of life and that patients at the end stage of life require spiritual support in addition to physical care, psychological care, and social support. Therefore, the purpose of this review is to examine the role of spirituality in the process of HSCT. METHOD: A systematic mixed studies review (SMSR) was based on Pluye and Hong's framework to understand the role of spirituality in patients' experiences while undergoing HSCT. We use the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement to report the results of integration. RESULTS: Fifteen original qualitative studies, 19 quantitative studies, and one mixed method study were included in the systematic mixed studies review. The evidence from the review revealed the following three themes: the spiritual experiences of HSCT patients, the spiritual coping styles of HSCT patients, and the spiritual need changes brought about by HSCT. DISCUSSION: Few medical institutions currently offer spiritual healing, although HSCT patients with different cultural backgrounds may have different spiritual experiences and spiritual coping styles. Psychotherapists or nurses should be considered to provide spiritual care for patients undergoing HSCT, to help patients cope with disease pressures, promote HSCT patients' comfort, and improve their quality of life.
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Transplante de Células-Tronco Hematopoéticas , Terapias Espirituais , Humanos , Qualidade de Vida , Apoio Social , EspiritualidadeRESUMO
Antimicrobial peptides play important roles in the immune response to pathogens and tumor cells; for this reason, they are being exploited for therapeutic use. In this study, we describe a Litopenaeus vannamei hemocyanin-derived peptide, denoted B11, which shares similar features with other anticancer peptides and attenuates the proliferation of cancer cells. Cell viability assay revealed that B11 significantly inhibited the proliferation of human cervical (HeLa), human hepatocellular carcinoma (HepG2), and human esophageal cancer (EC109) cancer cell lines, but not normal liver cell lines (T-antigen-immortalized human liver epithelial (THLE) cells or THLE-3), by inducing morphological changes, nuclear condensation, and margination, features which are indicative of apoptosis. Besides, peptide B11-induced apoptosis was confirmed by isothiocyanate-labeled Annexin V/propidium iodide (Annexin V-FITC/PI) double staining of HeLa cells. Moreover, cell uptake studies, confocal microscopy, and Western blot analysis revealed that rhodamine-labeled B11 permeated HeLa cells and localized to the mitochondria, causing mitochondria dysfunction through lost mitochondrial membrane potential, which consequently triggered the induction of apoptosis. Increased expression levels of caspase-9, caspase-3, and Bax (Bcl-2-associated X) proteins, coupled with a decrease in Bcl-2 (B-cell lymphoma 2) protein, confirmed that peptide B11 induced apoptosis via the mitochondrial pathway. Thus, the hemocyanin-derived peptide, B11, inhibits the proliferation of cancer cells by causing mitochondrial dysfunction and inducing apoptotic cell death, for which reason it could be explored as an anticancer peptide.
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Peptídeos Catiônicos Antimicrobianos/farmacologia , Antineoplásicos/farmacologia , Crustáceos/metabolismo , Hemocianinas/química , Animais , Peptídeos Catiônicos Antimicrobianos/síntese química , Peptídeos Catiônicos Antimicrobianos/química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Permeabilidade da Membrana Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Células HeLa , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Developmental dyslexia (DD) is a neurodevelopment disorder characterized by reading disabilities without apparent etiologies. Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a structural craniofacial malformation featured by isolated orofacial abnormalities. Despite substantial phenotypic differences, potential linkage between these two disorders has been suggested as prevalence of DD among NSCL/P patients was much higher than that in general populations. Previous neuroimaging studies observed impaired short-term memory in patients with DD and NSCL/P, respectively. Genetic factors have a fundamental role during neurodevelopment and craniofacial morphogenesis but there lacks of evidence to support the linkage between DD and NSCL/P at genetic level. A recent genome-wide association study in Chinese populations identified a number of genetic polymorphisms associated with NSCL/P. Herein, we selected three risk variants of NSCL/P namely rs8049367, rs4791774 and rs2235371, and performed association analysis with DD in a Chinese population consisting 631 elementary school-aged children with 288 dyslexic cases without NSCL/P and 343 healthy controls. After Bonferroni correction for multiple comparisons, the T allele of rs8049367 showed significant association with DD (OR=1.41, P=0.0085). It is an intergenic variant between CREBBP and ADCY9 located at 16p13.3. The CREBBP gene was reported to have an essential role during memory formation, although ADCY9 was involved in dental development. In future studies, understanding functional effects of rs8049367 on CERBBP and ADCY9 might contribute to explain underlying etiologies shared by DD and NSCL/P.
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Adenilil Ciclases/genética , Proteína de Ligação a CREB/genética , Fenda Labial/genética , Fissura Palatina/genética , Dislexia/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Alelos , Povo Asiático/genética , Criança , China , Feminino , Predisposição Genética para Doença , Humanos , MasculinoRESUMO
Preventing the occurrence of secondary caries serves as one of the significant issues in dental clinic, thus make it indispensable to improving the properties of conventional composite resin (CR) by developing a novel CR. In present study, two groups of experimental CRs loaded with different contents of fluoride-doped nano-zirconia fillers (25 wt% and 50 wt%) were fabricated. The surface topography, mechanical performance, fluoride release, antibacterial effect, aging property and cytotoxicity of the experimental CRs were evaluated subsequently. A uniform distribution of the F-zirconia fillers over the whole surface of resin matrix could be observed. The experimental CRs showed continuous fluoride release within 28 days, which was positively correlated with the content of F-zirconia fillers. Moreover, the amount of fluoride release increased in the acidic buffer. Addition of F-zirconia fillers could improve the color stability, wear resistance and microhardness of the experimental CRs, without reducing the flexure strength. Furtherly, the fluoride ions released continuously from the experimental CRs resulted in effective contact and antibacterial properties, while they showed no cytotoxicity. As a consequence, considerations can be made to employ this new kind of composite resin loaded with fluoride-doped nano-zirconia fillers to meet clinical requirements when the antimicrobial benefits are desired.
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Whey protein isolates (WPI) are known to have mineral-binding capacity to promote iron absorption. The aim of this study was to investigate the effect of iron ratio on the conformational structure of iron-bound whey protein isolate (WPI-Fe) and its thermodynamic stability. It was shown that the iron to protein ratio affects both the iron binding capacity of WPI and the iron valence state on the surface of WPI-Fe complexes. As the iron content increases, aggregation between protein molecules occurs. In addition, WPI-Fe nanoparticles have thermodynamic stability and Fe2+ has a high affinity with WPI for spontaneous exothermic reactions. This study demonstrates that WPI-Fe complexes can be used to efficiently deliver high-quality iron source (Fe2+) for future iron supplements.
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Ferro , Nanopartículas , Proteínas do Soro do Leite/química , TermodinâmicaRESUMO
Corn seeds are an essential element in agricultural production, and accurate identification of their varieties and quality is crucial for planting management, variety improvement, and agricultural product quality control. However, more than traditional manual classification methods are needed to meet the needs of intelligent agriculture. With the rapid development of deep learning methods in the computer field, we propose an efficient residual network named ERNet to identify hyperspectral corn seeds. First, we use linear discriminant analysis to perform dimensionality reduction processing on hyperspectral corn seed images so that the images can be smoothly input into the network. Second, we use effective residual blocks to extract fine-grained features from images. Lastly, we detect and categorize the hyperspectral corn seed images using the classifier softmax. ERNet performs exceptionally well compared to other deep learning techniques and conventional methods. With 98.36% accuracy rate, the result is a valuable reference for classification studies, including hyperspectral corn seed pictures.
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The grooming behavior of honeybees serves as a crucial auto-protective mechanism against Varroa mite infestations. Compared to Apis mellifera, Apis cerana demonstrates more effective grooming behavior in removing Varroa mites from the bodies of infested bees. However, the underlying mechanisms regulating grooming behavior remain elusive. In this study, we evaluated the efficacy of the auto-grooming behavior between A. cerana and A. mellifera and employed RNA-sequencing technology to identify differentially expressed genes (DEGs) in bee brains with varying degrees of grooming behavior intensity. We observed that A. cerana exhibited a higher frequency of mite removal between day 5 and day 15 compared to A. mellifera, with day-9 bees showing the highest frequency of mite removal in A. cerana. RNA-sequencing results revealed the differential expression of the HTR2A and SLC17A8 genes in A. cerana and the CCKAR and TpnC47D genes in A. mellifera. Subsequent homology analysis identified the HTR2A gene and SLC17A8 gene of A. cerana as homologous to the HTR2A gene and SLC17A7 gene of A. mellifera. These DEGs are annotated in the neuroactive ligand-receptor interaction pathway, the glutamatergic synaptic pathway, and the calcium signaling pathway. Moreover, CCKAR, TpnC47D, HTR2A, and SLC17A7 may be closely related to the auto-grooming behavior of A. mellifera, conferring resistance against Varroa infestation. Our results further explain the relationship between honeybee grooming behavior and brain function at the molecular level and provide a reference basis for further studies of the mechanism of honeybee grooming behavior.
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Encéfalo , Asseio Animal , Transcriptoma , Varroidae , Animais , Abelhas/parasitologia , Abelhas/genética , Varroidae/genética , Encéfalo/parasitologia , Encéfalo/metabolismo , Infestações por Ácaros/genética , Infestações por Ácaros/veterinária , Infestações por Ácaros/parasitologia , Perfilação da Expressão Gênica/métodosRESUMO
Introduction: Calcitonin gene-related peptide (CGRP) is involved in trigeminal neuralgia and migraine, and measuring the CGRP concentration in the serum is crucial for the early prediction of these conditions. Current methods for CGRP detection are primarily radioimmunoassay, which needs radioactive substances and enzyme-linked immunosorbent assays (ELISAs) which need long detection time and some have a narrow detection range. Methods: The genes of anti-CGRP antibody variable regions were cloned into pDong1 vector to obtain pDong1/Fab-CGRP, with which phage-Fab was prepared, and the concentration of CGRP was detected by competitive ELISA. The pDong1/Fab-CGRP was modified to obtain pDong1/OS-CGRP, with which the co-expression solution containing phage-displayed heavy chain variable fragments (phage-VH) and light chain was obtained. CGRP was detected by OS-ELISA based on phage-VH, antibody light chain, and anti-light chain antibody. The VL gene was cloned into the pMAL vector to obtain pMAL-VL (CGRP), with which maltose binding protein fused with VL (MBP-VL) was prepared. CGRP was detected by OS-ELISA employing MBP-VL and phage-VH. Results: OS-ELISAs that measure the CGRP concentration by quantifying the interaction between variable regions were investigated. OS-ELISA using phage-VH and secreted light chains in the same culture system exhibited a limit of detection (LOD) of 0.05 nM, offering higher sensitivity than competitive assay with an LOD of 0.75 nM, whereas using phage-VH and separately prepared MBP-VL exhibited an LOD of 0.15 nM and a broader detection range of 0.15-500 nM than competitive ELISA, whose detection range was 0.75-10 nM. Discussion: The combination of the two OS assays achieved high sensitivity and a broad detection range for CGRP, which may have significance in clinical applications.
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Water resources are important factors limiting social and economic development, so how to ensure the coordination between economic development and water resources-ecological management capacity has become a key issue that needs to be addressed urgently for China's high-quality economic development. This paper used nighttime light data as proxy variables of economic development to calculate the coupling coordination degree between provincial economic development and water resources-ecological management capacity in China from 2004 to 2019 based on the coupling coordination degree model; w constructed a spatial econometric model to explore the spatial correlation and influencing factors between economic development and water resources-ecological management capacity. The results are shown in the following: (1) The overall level of China's economic development is on an upward trend, but the regional development is unbalanced, showing a decreasing spatial pattern distribution of the eastern coastal region-mid-western region-far-western region. (2) The level of water resources-ecological management capacity is low, and the spatial distribution shows a decreasing trend in the far west-central and western-eastern coastal regions. (3) The level of coupling and coordination between economic development and water resources-ecological management capacity rises from a mild imbalance level to a little imbalance level, and the spatial distribution is consistent with the spatial distribution of economic development. (4) The factors influencing the level of coupling and coordination of inter-provincial economic development and water resources-ecological management capacity in China mainly involve the population scale, technological progress, affluence, and foreign direct investment. Each province and city should take into account its own actual situation and develop targeted measures to promote the coordinated development of economic development and the water resources-ecological management capacity.
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Desenvolvimento Econômico , Recursos Hídricos , Água , Iluminação , China , CidadesRESUMO
BACKGROUND: Rosai-Dorfman disease (RDD) is a rare, non-Langerhans cell histiocytosis of unknown etiology. we report a very rare case of recurrent central nervous system RDD with KRAS gene mutation and review the literature to improve our understanding of this disease. CASE PRESENTATION: A 19-year-old male patient was admitted to our hospital for headache. Cranial magnetic resonance imaging revealed a mass of abnormal signal shadows in the prepontine cistern. The mass was surgically removed and the patient was consequently diagnosed with intracranial Rosai-Dorfman disease. Seven months later, pathological examination confirmed that the RDD had recurred. Next-generation sequencing found KRAS mutation in exon 4 (C.351A > C. P. K117n). CONCLUSION: RDD of the CNS has no distinct clinical manifestations and imaging characteristics, and the final diagnosis should be based on the results of the pathological examination. Although RDD is not currently classified as a neoplastic disorder, some evidence of clonality has changed our understanding of it. Follow up examinations over a long period are necessary to determine the efficacy of treatment.
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Histiocitose Sinusal , Humanos , Masculino , Adulto Jovem , Sistema Nervoso Central/patologia , Diagnóstico Diferencial , Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/genética , Histiocitose Sinusal/patologia , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genéticaRESUMO
Human papilloma virus (HPV) infection and its associated disease are major problems affecting millions of individuals around the world. The distribution of HPV genotypes is specific to different areas and different populations. Therefore, understanding the prevalence and genotype distribution of HPV in different populations in different geographical regions is essential to optimize HPV vaccination strategies and to maximize vaccine effects. In this study, 34,076 women from January 2016 to July 2022 were retrospectively analyzed at Liaocheng People's Hospital. Of these, 7540 women were high-risk HPV positive and the infection rate was 22.13%. The top ten genotypes were as follows in descending order: HPV16, HPV52, HPV58, HPV53, HPV39, HPV59, HPV66, HPV51, HPV18, and HPV56 and the least frequent genotypes were, in order, HPV 26, HPV45, and HPV82. The HPV16 positive infection rate was 25.37% and was reduced with the increase in the number of individuals who had undergone HPV screening. The HPV52 infection rate increased with increasing numbers of individuals undergoing HPV screening, and then remained unchanged. The proportion of 20-29-year-olds among all positive women began to decrease since the vaccine was available in 2018. The 30-39-year-old group accounted for the highest percentage of positive women, and the 50-59-year-old group of HPV-positive women with cervical cancer accounted for most infections. This study confirmed that HPV16, HPV52, HPV 58, and HPV53 is widely distributed in this population and the total HR-HPV infection rate remains high in this region. Our findings indicate that prevention of HPV infection in this region still faces important challenges.
Assuntos
Infecções por Papillomavirus , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Infecções por Papillomavirus/prevenção & controle , Prevalência , Estudos Retrospectivos , Genótipo , China/epidemiologia , Papillomaviridae/genéticaRESUMO
Purpose: Insufficient osseointegration and implant-associated infection are major factors in the failure of Ti-based implants, thus spurring scientists to develop multifunctional coatings that are better suited for clinical requirements. Here, a new biomimetic micro/nanoscale topography coating combined with antibacterial copper was simultaneously designed for Ti-based implant surfaces by adopting a hybrid approach combining plasma electrolytic oxidation and hydrothermal treatment. Results: The biological interactions between this biofunctionalized material interface and stem cells promoted cellular adhesion and spreading during initial attachment and supported cellular proliferation for favorable biocompatibility. Bone marrow mesenchymal stem cells (BMMSCs) on the coating displayed enhanced cellular mineral deposition ability, higher alkaline phosphatase activity, and upregulated expression of osteogenic-related markers without the addition of osteoinductive chemical factors, which improved osseointegration. More interestingly, this new coating reduced the viability of oral pathogens (Fusobacterium nucleatum and Porphyromonas gingivalis)-the primary causes of implant-associated infections as indicated by damage of cellular structures and decreased population. This is the first study investigating the antibacterial property of dental implants modified by a hybrid approach against oral pathogens to better mimic the oral environment. Conclusion: These findings suggest that biofunctionalization of the implant coating by surface modification methods and the incorporation of antibacterial copper (Cu) offer superior osteogenesis capability and effective antibacterial activity, respectively. These strategies have great value in orthopedic and dental implant applications.