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As children are a special group, the optimal management approach for pediatric patients with flatfoot after subtalar arthroereisis remains unclear. This study aims to explore the clinical effects of early intensified follow-up compared to conventional follow-up for such patients. We conducted a prospective study on 83 pediatric flatfoot patients from January 2019 to June 2022. Patients were divided into early intensive follow-up and routine follow-up groups. The study compared preoperative, 3 months postoperative, and 1-year postoperative Maryland Foot Function Scores, American Orthopedic Foot and Ankle Society (AOFAS) scores, and Visual Analogue Scale (VAS) scores, etc. At 3 months postoperatively, the early intensified follow-up group showed significantly higher Maryland Foot Score and surgery satisfaction compared to the conventional follow-up group. There were no statistical differences in other indicators at 3 months postoperatively, and all observed indicators at 1 year postoperatively. In conclusion, early intensive follow-up can accelerate the functional recovery process of pediatric flatfoot patients undergoing subtalar arthroereisis and improve surgical satisfaction. Increasing medical resource investment for enhanced postoperative management is valuable for such patients.
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Pé Chato , Humanos , Pé Chato/cirurgia , Feminino , Masculino , Criança , Estudos Prospectivos , Adolescente , Resultado do Tratamento , Articulação Talocalcânea/cirurgia , Seguimentos , Assistência ao Convalescente/métodos , Assistência ao Convalescente/normas , Assistência ao Convalescente/estatística & dados numéricosRESUMO
BACKGROUND: Adequate death preparation positively influences families' experience before death and during bereavement. However, how to prepare families in non-Western cultures has received scant attention. AIM: To explore family caregivers' experiences in preparing for a relative's death in specialist palliative care in Taiwan. DESIGN: A qualitative study employing reflexive thematic analysis of data collected from semi-structured interviews was conducted. SETTING/PARTICIPANTS: Twenty-two family caregivers from seven hospitals participated. RESULTS: The overarching theme was 'getting everything right to have no regrets between the dead and the living'. We developed two themes to explain preparations for the time surrounding and after the death, including the deceased' afterlife: (1) 'having a good ending but not the end of the relationship', which addresses preparations for the death itself, the funeral, the afterlife and maintaining connections and (2) 'using religious beliefs and cultural norms to guide preparation', which explores perceptions of a good death, including refrain from strong emotions before and after the death. CONCLUSION: Funeral arrangements, enhancing the deceased's afterlife and maintaining connections to the deceased are crucial for families' experiences which can be impacted by actions they take as they prepare for the death. A culturally appropriate death is beneficial for the dying relative which includes preparing to not show strong emotions during and after the death. These insights inform the importance of the cultural context in death preparation in Taiwan and provide perspectives for palliative care beyond Western culture, potentially benefiting Chinese populations, predominantly East Asian and Buddhist societies.
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BACKGROUND: Understanding the role of cytokines in tooth development is critical for advancing dental tissue engineering. Fibroblast growth factor 9 (FGF9) is the only FGF consistently expressed throughout dental epithelial tissue, from the initiation of tooth bud formation to tooth maturation. However, mice lacking Fgf9 (Fgf9-/-) surprisingly show no obvious abnormalities in tooth development, suggesting potential compensation by other FGFs. Here we report findings from an Fgf9S99N mutation mouse model, a loss-of-function mutation with a dominant negative effect. Our study reveals that Fgf9 is crucial for dental epithelial stem cell (DESC) survival and enamel formation. METHODS: To dissect the role of Fgf9 in tooth development, we performed the micro-CT, histomorphological analysis and gene expression assay in mice and embryos with S99N mutation. In addition, we assessed the effect of FGF9 on the DESC survival and dental epithelial differentiation by DESC sphere formation assay and tooth explant culture. Cell/tissue culture methods, gene expression analysis, specific inhibitors, and antibody blockage analysis were employed to explore how Fgf9 regulates enamel differentiation and DESC survival through both direct and indirect mechanisms. RESULTS: The Fgf9S99N mutation in mice led to reduced ameloblasts, impaired enamel formation, and increased apoptosis in the cervical loop (CL). DESC sphere culture experiments revealed that FGF9 facilitated DESC survival via activating ERK/CREB signaling, without affecting cell proliferation. Furthermore, in vitro tissue culture experiments demonstrated that FGF9 promoted enamel formation in a manner dependent on the presence of mesenchyme. Interestingly, FGF9 stimulation inhibited enamel formation in isolated enamel epithelia and DESC spheres. Further investigation revealed that FGF9 supports DESC survival and promotes amelogenesis by stimulating the secretion of FGF3 and FGF10 in dental mesenchymal cells via the MAPK/ERK signaling pathway. CONCLUSIONS: Our study demonstrates that Fgf9 is essential for DESC survival and enamel formation. Fgf9 performs as a dual-directional regulator of the dental enamel epithelium, not only inhibiting DESC differentiation into ameloblasts to preserve the stemness of DESC, but also promoting ameloblast differentiation through epithelial-mesenchymal interactions.
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Esmalte Dentário , Células Epiteliais , Fator 9 de Crescimento de Fibroblastos , Células-Tronco , Animais , Fator 9 de Crescimento de Fibroblastos/metabolismo , Fator 9 de Crescimento de Fibroblastos/genética , Camundongos , Esmalte Dentário/metabolismo , Células-Tronco/metabolismo , Células-Tronco/citologia , Células Epiteliais/metabolismo , Incisivo/metabolismo , Sobrevivência Celular , Diferenciação CelularRESUMO
Background: Increasing attention to liver-bone crosstalk has spurred interest in targeted interventions for various forms of osteoporosis. Liver injury induced by different liver diseases can cause an imbalance in bone metabolism, indicating a novel regulatory paradigm between the liver and bone. However, the role of the liver-bone axis in both primary and secondary osteoporosis remains inadequately elucidated. Therefore, exploring the exact regulatory mechanisms of the liver-bone axis may offer innovative clinical approaches for treating diseases associated with the liver and bone. Methods: Here, we summarize the latest research on the liver-bone axis by searching the PubMed and Web of Science databases and discuss the possible mechanism of the liver-bone axis in different types of osteoporosis. The literature directly reporting the regulatory role of the liver-bone axis in different types of osteoporosis from the PubMed and Web of Science databases has been included in the discussion of this review (including but not limited to the definition of the liver-bone axis, clinical studies, and basic research). In addition, articles discussing changes in bone metabolism caused by different etiologies of liver injury have also been included in the discussion of this review (including but not limited to clinical studies and basic research). Results: Several endocrine factors (IGF-1, FGF21, hepcidin, vitamin D, osteocalcin, OPN, LCAT, Fetuin-A, PGs, BMP2/9, IL-1/6/17, and TNF-α) and key genes (SIRT2, ABCB4, ALDH2, TFR2, SPTBN1, ZNF687 and SREBP2) might be involved in the regulation of the liver-bone axis. In addition to the classic metabolic pathways involved in inflammation and oxidative stress, iron metabolism, cholesterol metabolism, lipid metabolism and immunometabolism mediated by the liver-bone axis require more research to elucidate the regulatory mechanisms involved in osteoporosis. Conclusion: During primary and secondary osteoporosis, the liver-bone axis is responsible for liver and bone homeostasis via several hepatokines and osteokines as well as biochemical signaling. Combining multiomics technology and data mining technology could further advance our understanding of the liver-bone axis, providing new clinical strategies for managing liver and bone-related diseases.The translational potential of this article is as follows: Abnormal metabolism in the liver could seriously affect the metabolic imbalance of bone. This review summarizes the indispensable role of several endocrine factors and biochemical signaling pathways involved in the liver-bone axis and emphasizes the important role of liver metabolic homeostasis in the pathogenesis of osteoporosis, which provides novel potential directions for the prevention, diagnosis, and treatment of liver and bone-related diseases.
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This study investigated the possible mechanisms of microRNA-124a on the differentiation of bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanism. ß-Thiol ethanol induced Notch1 mRNA expression, microRNA-124a inhibitor reduced the effects of ß-thiol ethanol on Notch1 mRNA expression in BMSCs. Baicalin induced Hes1 mRNA expression, and microRNA-124a inhibitor reduced the effects of baicalin on Hes1 mRNA expression in BMSCs. Si-Notch1 suppressed Hes1 mRNA expression in BMSCs. Baicalin increased the effects of Notch1 on Hes1 mRNA expression in BMSCs. Si-Notch1 increased cell growth of BMSCs. Baicalin reduced the effects of si-Notch1 on cell growth and the differentiation of BMSCs. We demonstrated that microRNA-124a promoted the differentiation of BMSCs into neurons through Notch/Hes1 signal pathway.
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Diferenciação Celular , Células-Tronco Mesenquimais , MicroRNAs , Neurônios , Receptor Notch1 , Transdução de Sinais , Fatores de Transcrição HES-1 , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Animais , Receptor Notch1/metabolismo , Receptor Notch1/genética , Neurônios/metabolismo , Neurônios/citologia , Fatores de Transcrição HES-1/metabolismo , Fatores de Transcrição HES-1/genética , Células da Medula Óssea/metabolismo , Células da Medula Óssea/efeitos dos fármacos , Flavonoides/farmacologia , Proliferação de Células/efeitos dos fármacos , Ratos , Células Cultivadas , Receptores Notch/metabolismo , Receptores Notch/genética , Ratos Sprague-DawleyRESUMO
Targeted protein degradation (TPD) is an emerging therapeutic paradigm aimed at eliminating the disease-causing protein with aberrant expression. Herein, we report a new approach to inducing intracellular glutathione peroxidase 4 (GPX4) protein degradation to trigger ferroptosis by bridging the target protein to heat shock protein 90 (HSP90), termed HSP90 interactome-mediated proteolysis targeting chimera (HIM-PROTAC). Different series of HIM-PROTACs were synthesized and evaluated, and two of them, GDCNF-2/GDCNF-11 potently induced ferroptosis via HSP90-mediated ubiquitin-proteasomal degradation of GPX4 in HT-1080 cells with DC50 values of 0.18 and 0.08 µM, respectively. In particular, GDCNF-11 showed 15-fold more ferroptosis selectivity over GPX4 inhibitor ML162. Moreover, these two degraders effectively suppress tumor growth in the mice model with relatively low toxicity as compared to the combination therapy of GPX4 and HSP90 inhibitors. In general, this study demonstrated the feasibility of degrading GPX4 via HSP90 interactome, and thus provided a significant complement to existing TPD strategies.
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Ferroptose , Proteínas de Choque Térmico HSP90 , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Proteólise , Ferroptose/efeitos dos fármacos , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/antagonistas & inibidores , Humanos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/antagonistas & inibidores , Proteólise/efeitos dos fármacos , Animais , Camundongos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Camundongos Nus , Camundongos Endogâmicos BALB C , Quimera de Direcionamento de ProteóliseRESUMO
Thio-benzothioxanthene imide (BTXI) exhibits long excited state lifetime (τT = 17.7 µs) and high ISC efficiency (ΦΔ = 97%). For the first time, BTXI derivatives were used as photosensitizers for triplet-triplet annihilation upconversion, achieving the highest efficiency of 13.8%. In addition, thio-BTXI derivatives were used as photoinitiators for photopolymerization, resulting in a series of green light-activated radical polymerization systems.
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Photodynamic therapy (PDT) plays a crucial role in treating cancer and major infectious diseases. However, the hypoxic microenvironment and deep-seated tumors often compromise the effectiveness of photosensitizers (PSs). PSs primarily generate type-II reactive oxygen species (ROS), which are limited under hypoxic conditions. Pyridinium salts frequently exhibit critical dark toxicity in vitro. Moreover, PDT alone often fails to achieve optimal anti-tumor effects compared to its combined application with photothermal therapy (PTT). To address these issues, we replaced pyridinium with quinolinium, significantly reducing dark toxicity. Additionally, the incorporation of benzophenone enhanced ROS generation, achieving a synergistic effect of type-I and type-II PDT. Fine-tuning the conjugated structure enhanced the donor-acceptor (D-A) intensity, while the stretching vibrations of carbon-carbon double bonds and carbon-nitrogen triple bonds red-shifted the excitation wavelength to the near-infrared (NIR) region and improved the photothermal conversion efficiency (PCE). This strategy provides a molecular design approach for achieving synergy between PDT and PTT. The synthesized four NIR-emitting aggregation-induced emission quinolinium salts exhibited mitochondrial targeting ability and low dark toxicity. Among them, FCN-TPAQ-BP showed excellent ROS generation capability, a PCE of 39.2%, good biocompatibility, and low dark toxicity, making it an ideal candidate for enhancing PDT's antitumor efficacy.
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Antineoplásicos , Benzofenonas , Raios Infravermelhos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Espécies Reativas de Oxigênio , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Humanos , Benzofenonas/química , Benzofenonas/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Espécies Reativas de Oxigênio/metabolismo , Animais , Estrutura Molecular , Sobrevivência Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
Gastric cancer is a common malignant tumor, and its incidence rate ranks first among malignant tumors of the digestive tract, seriously endangering human physical and mental health. Changes in the physiological state of gastric cancer patients can bring about many physical and psychological symptoms and have a serious impact on their quality of life. Symptom clusters are 2 or more concurrently occurring and interrelated symptoms, with the core symptoms within the cluster remaining stable over time and the symptoms in the cluster being independent of each other. The prerequisite for solving this problem is to screen out appropriate symptom assessment tools according to the clinical situation. The aim of this study was to provide a reference for the development of assessment tools suitable for symptom clusters of gastric cancer patients in China, and to provide evidence for the subsequent optimization of symptom management and some clinical decisions. The contents, application, advantages, and disadvantages of symptom cluster assessment tools for gastric cancer patients in China and abroad were reviewed, and the basic situation and contents of each assessment tool were compared. In China, most of the assessment tools used in domestic gastric cancer research institutes were imported from foreign scales, with a long time span and low specificity for symptoms in various stages of disease development at present. Scholars should be encouraged to develop time-specific assessment tools for the disease characteristics of gastric cancer patients in China, and actively explore the pathogenesis and influencing factors of symptom clusters in this population.
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Qualidade de Vida , Neoplasias Gástricas , Avaliação de Sintomas , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Humanos , China/epidemiologia , Avaliação de Sintomas/métodos , Análise por Conglomerados , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Measles and rubella are vaccine-preventable diseases targeted for elimination in most World Health Organization regions, and China is considered to have momentum towards measles elimination. Therefore, this study aimed to assess the population immunity levels against measles and rubella in Zhejiang Province in China in order to provide valuable insights for informing future public health measures and contributing to the ongoing global campaign against these diseases. MATERIALS AND METHODS: A cross-sectional serological survey was conducted in 2022. A total of 2740 blood samples were collected from healthy individuals spanning the age range of 0-59 years, representing diverse demographic strata across 11 prefectures in Zhejiang Province in China. The sera were tested for measles and rubella IgG antibodies to determine positivity rates and geometric mean concentrations (GMCs). RESULTS: The overall positivity rate for the measles IgG antibody was 85.3%, with a GMC of 588.30 mIU/mL. The positivity rate for the rubella IgG antibody was 70.9%, and the GMC was 35.30 IU/mL. Measles IgG antibody positivity rates across the 0-11 months, 12-23 months, 24-35 months, 3-5 years, 6-9 years, 10-14 years, 15-19 years, 20-29 years, and 30-59 years age groups were 63.1%, 92.5%, 97.0%, 94.0%, 85.8%, 77.3%, 86.9%, 84.9%, and 88.7%, respectively (trend χ2 = 118.34, p < 0.001). Correspondingly, rubella antibody positivity rates for these same age brackets were 55.9%, 87.9%, 94.7%, 88.2%, 69.9%, 54.2%, 72.6%, 67.5%, and 74.3% (trend χ2 = 199.18, p < 0.001). Both univariate and multivariate analyses consistently demonstrated that age, immunization history, and differing economic levels were significant factors contributing to variations in antibody levels. CONCLUSIONS: The seroprevalence of measles and rubella was lower than that required for herd immunity. Periodic vaccination campaigns should be launched to increase immunity.
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BACKGROUND: Recent studies have reported that helix B surface polypeptide (HBSP), an erythropoietin derivative, exhibits strong tissue protective effects, independent of erythropoietic effects, in a renal ischemia-reperfusion (IR) injury model. Meanwhile, the transforming growth factor-ß (TGF-ß) superfamily member glial cell line-derived neurotrophic factor (GDNF) demonstrated protective effect on podocytes in vitro. Using a rat puromycin aminonucleoside nephropathy (PAN) model, this study observed the renal protective effect of HBSP and investigated its renal protective effect on podocytes and mechanism related to GDNF. METHODS: Rats nephropathy model was induced by injection of 60 mg/kg of PAN via the tail vein. Rats in the PAN + HBSP group were injected intraperitoneally with HBSP (8 nmol/kg) 4 h before the model was induced, followed by intraperitoneal injections of HBSP once every 24 h for 7 consecutive days. The 24-hour urinary protein level was measured once every other day, and blood and renal tissue samples were collected on the 7th day for the examination of renal function, complete blood count, renal pathological changes and the expression levels of GDNF. RESULTS: Compared with the control group, the PAN nephropathy rat model showed a large amount of urinary protein. The pathological manifestations were mainly extensive fusion and disappearance of foot processes, along with vacuolar degeneration of podocytes and their separation from the glomerular basement membrane. GDNF expression was upregulated. Compared with the PAN + vehicle group, the PAN + HBSP group showed decreased urinary protein (p < 0.05). Pathological examination revealed ameliorated glomerular injury and vacuolar degeneration of podocytes. The expression of GDNF in the PAN nephropathy group was increased, when compared with the control group. The greatest expression of GDNF observed in the PAN + HBSP group (p < 0.05). CONCLUSIONS: The expression of GDNF in the kidney of PAN rat model was increased. HBSP reduced urinary protein, ameliorated pathological changes in renal podocytes, increased the expression of GDNF in the PAN rat model. HBSP is likely to exert its protective effects on podocytes through upregulation of GDNF expression.
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Modelos Animais de Doenças , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Nefropatias , Podócitos , Puromicina Aminonucleosídeo , Ratos Sprague-Dawley , Animais , Ratos , Podócitos/efeitos dos fármacos , Podócitos/patologia , Podócitos/metabolismo , Masculino , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Nefropatias/patologia , Rim/patologia , Rim/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Eritropoetina , Fragmentos de PeptídeosRESUMO
We report the synthesis, crystal structure, magnetization and specific heat studies of YCo3(OH)6.55Br2.45single crystal. YCo3(OH)6.55Br2.45crystallizes in trigonal structure, in which Co2+ions form a perfect kagomé lattice. The magnetic susceptibility reveals successive magnetic transitions at 6.5 and 7.8 K and the Curie-Weiss fitting demonstrates that YCo3(OH)6.55Br2.45has strong antiferromagnetic coupling and pronounced magnetic frustration effect. Specific heat data suggest that low-Tmagnetic transitions are attributed to antiferromagnetic ordering of Co2+ions and the magnetic entropy points to effective 1/2 spin in the system. These results indicate that an unusual magnetic ordering state with effective spin-1/2 is realized in kagomé lattice system YCo3(OH)6.55Br2.45.
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Previous research has revealed that platelets promote tumor metastasis by binding to circulating tumor cells (CTCs). However, the role of platelets in epithelial-mesenchymal transition (EMT) of cancer cells at the primary tumor site, the crucial initial step of tumor metastasis, remains to be elucidated. Here, we found that platelet releasate enhanced EMT and motility of hepatocellular carcinoma (HCC) cells via AMPK/mTOR-induced autophagy. RNA-seq indicated that platelet releasate altered TGF-ß signaling pathway of cancer cells. Inhibiting TGFBR or deleting platelet TGF-ß1 suppressed AMPK/mTOR pathway activation and autophagy induced by platelet releasate. Compared with Pf4cre-; Tgfb1fl/fl mice, HCC orthotopic models established on Pf4cre+; Tgfb1fl/fl mice showed reduced TGF-ß1 in primary tumors, which corresponded with decreased cancer cell EMT, autophagy, migration ability and tumor metastasis. Inhibition of autophagy via Atg5 knockdown in cancer cells negated EMT and metastasis induced by platelet-released TGF-ß1. Clinically, higher platelet count correlated with increased TGF-ß1, LC3 and N-cad expression in primary tumors of HCC patients, suggesting a link between platelets and HCC progression. Our study indicates that platelets promote cancer cell EMT in the primary tumor and HCC metastasis through TGF-ß1-induced HCC cell autophagy via the AMPK/mTOR pathway. These findings offer novel insights into the role of platelets in HCC metastasis and the potential therapeutic targets for HCC metastasis.
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Autofagia , Plaquetas , Carcinoma Hepatocelular , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas , Transdução de Sinais , Fator de Crescimento Transformador beta1 , Animais , Humanos , Masculino , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Plaquetas/metabolismo , Plaquetas/patologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Metástase Neoplásica , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta1/genéticaRESUMO
Spotted seabass (Lateolabrax maculatus) is the second largest maricultural fish species in China and is the main trigger of food-related allergic reactions. Nevertheless, studies on the allergens of L. maculatus are limited. This study aimed to characterize pan-allergen parvalbumin from L. maculatus. Two proteins of about 11 kDa were purified and confirmed as parvalbumins by mass spectrometry. The IgG- and IgE-binding activities were evaluated through an immunoblotting assay. The molecular characteristics of ß-parvalbumin were investigated by combining proteomics, genomics, and immunoinformatics approaches. The results indicated that ß-parvalbumin consists of 109 amino acids with a molecular weight of 11.5 kDa and is the major allergen displaying strong IgE-binding capacity. In silico analysis and a dot blotting assay confirmed seven linear B cell epitopes distributed mainly on α-helixes and the calcium-binding loops. In addition, the cross-reactivity among 26 commonly consumed fish species was analyzed. The in-house generated anti-L. maculatus parvalbumin polyclonal antibody recognized 100% of the 26 fish species, demonstrating cross-reactivity and better binding capacity than the anticod parvalbumin antibody. Together, this study provides an efficient protocol to characterize allergens with multiomics methods and supports parvalbumin from L. maculatus as a candidate for fish allergen determination and allergy diagnosis.
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Alérgenos , Reações Cruzadas , Proteínas de Peixes , Hipersensibilidade Alimentar , Imunoglobulina E , Parvalbuminas , Parvalbuminas/imunologia , Parvalbuminas/química , Parvalbuminas/genética , Animais , Alérgenos/imunologia , Alérgenos/genética , Alérgenos/química , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Proteínas de Peixes/genética , Imunoglobulina E/imunologia , Hipersensibilidade Alimentar/imunologia , Bass/imunologia , Bass/genética , Epitopos/imunologia , Epitopos/química , Humanos , Proteômica , Imunoglobulina G/imunologia , Sequência de Aminoácidos , MultiômicaRESUMO
OBJECTIVE: Glioma is a central nervous system tumor arising from glial cells. Despite significant advances in diagnosis and treatment, most patients with high-grade gliomas have a poor prognosis. Many studies have shown that long noncoding RNAs (lncRNAs) may play important roles in the development, progression and treatment of many tumors, including gliomas. Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma. Therefore, we hope that by studying differentially expressed lncRNAs (DElncRNAs) in glioma, we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients. METHODS: First, the expression of lncRNAs in 5 normal brain (NB) tissues and 10 glioma tissues was examined by RNA sequencing (RNA-seq). Next, we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas (TCGA) database to assess the prognostic value of these variables. Finally, functional analysis of the DElncRNAs was performed by means of Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. RESULTS: RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma (LGG) and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma (GBM). Among them, AL355974.3 was the most upregulated lncRNA. LINC00632 was the most downregulated lncRNA. Second, LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database. Finally, bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways, such as cell metabolic and developmental processes. CONCLUSION: Our findings provide evidence that AL355974.3 may be a new biomarker for glioma.
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We developed and experimentally realized a scheme of optical nonreciprocity (ONR) by using degenerate two-level atoms embedded in an optical ring cavity. For the degenerate transition Fg = 4 â Fe = 3, we first studied the cavity-transmission property in different coupling field configurations and verified that under the strong-coupling regime, the single-dark-state peak formed by electromagnetically induced transparency (EIT) showed ONR. The stable ground-state Zeeman coherence for Λ-chains involved in the degenerate two-level system was found to be important in the formation of intracavity EIT. However, different from the three-level atom-cavity system, in the degenerate two-level system, the ONR effect based on intracavity EIT occurred only at a low probe intensity, because the cavity-atom coupling strength was weakened in the counter-propagating probe and coupling field configuration. Furthermore, ONR transmission with a high contrast and linewidth-narrowing was experimentally demonstrated.
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Coumarins are natural products with benzopyran ring as the parent nucleus. Numerous coumarin derivatives exhibit a variety of pharmacological activities, including antibacterial, anti-inflammatory, antitumor, anti-coagulant, anti-osteoporotic, and insecticidal activities. Therefore, they play an important role in both medicine and agriculture. The development and utilization of coumarin derivatives have attracted increasing attention. The advancement of gene sequencing technology and the rapid progress in synthetic bio-logy have led to significant advancement in the biosynthesis of coumarin derivatives, and has received increasing attention from global researchers. This paper presents a comprehensive overview of the key biosynthesis-related enzymes of coumarin derivatives, such as cytochrome P450 enzyme(CYP450), prenyltransferase(PT), UDP-glucosyltransferase(UGT). Additionally, the pharmacological activities of these enzymes, including anti-tumor, anti-inflammatory, antioxidant, and antibacterial activities, are systematically summarized. This review aims to provide a valuable reference for the biosynthesis of coumarin derivatives and further exploration of their medicinal potential.
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Cumarínicos , Cumarínicos/química , Cumarínicos/farmacologia , Cumarínicos/metabolismo , Humanos , Animais , Dimetilaliltranstransferase/metabolismo , Dimetilaliltranstransferase/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Glucosiltransferases/genética , Glucosiltransferases/metabolismoRESUMO
OBJECTIVES: To determine the pharmacological impact of hesperidin, the main component of Citri Reticulatae Pericarpium, on depressive behavior and elucidate the mechanism by which hesperidin treats depression, focusing on the gut-brain axis. METHODS: Fifty-four Sprague Dawley male rats were randomly allocated to 6 groups using a random number table, including control, model, hesperidin, probiotics, fluoxetine, and Citri Reticulatae Pericarpium groups. Except for the control group, rats in the remaining 5 groups were challenged with chronic unpredictable mild stress (CUMS) for 21 days and housed in single cages. The sucrose preference test (SPT), immobility time in the forced swim test (FST), and number in the open field test (OFT) were performed to measure the behavioral changes in the rats. Enzyme-linked immunosorbent assay was used to determine the levels of 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) in brain tissue, and the histopathology was performed to evaluate the changes of colon tissue, together with sequencing of the V3-V4 regions of 16S rRNA gene on feces to explore the changes of intestinal flora in the rats. RESULTS: Compared to the control group, the rats in the model group showed notable reductions in body weight, SPF, and number in OFT (P<0.01). Hesperidin was found to ameliorate depression induced by CUMS, as seen by improvements in body weight, SPT, immobility time in FST, and number in OFT (P<0.05 or P<0.01). Regarding neurotransmitters, it was found that at a dose of 50 mg/kg hesperidin treatment upregulated the levels of 5-HT and BDNF in depressed rats (P<0.05). Compared to the control group, the colon tissue of the model group exhibited greater inflammatory cell infiltration, with markedly reduced numbers of goblet cells and crypts and were significantly improved following treatment with hesperidin. Simultaneously, the administration of hesperidin demonstrated a positive impact on the gut microbiome of rats treated with CUMS, such as Shannon index increased and Simpson index decreased (P<0.01), while the abundance of Pseudomonadota and Bacteroidota increased in the hesperidin-treated group (P<0.05). CONCLUSION: The mechanism responsible for the beneficial effects of hesperidin on depressive behavior in rats may be related to inhibition of the expressions of BDNF and 5-HT and preservation of the gut microbiota.
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Anomalous Hall effect (AHE), one of the most important electronic transport phenomena, generally appears in ferromagnetic materials but is rare in materials without magnetic elements. Here, a study of La3MgBi5 is presented, whose band structure carries multitype Dirac fermions. Although magnetic elements are absent in La3MgBi5, the signals of AHE can be observed. In particular, the anomalous Hall conductivity is extremely large, reaching 42,356 Ω-1 cm-1 with an anomalous Hall angle of 8.8%, the largest one that has been observed in the current AHE systems. The AHE is suggested to originate from the combination of skew scattering and Berry curvature. Another unique property discovered in La3MgBi5 is the axial diamagnetism. The diamagnetism is significantly enhanced and dominates the magnetization in the axial directions, which is the result of the restricted motion of the Dirac fermion at the Fermi level. These findings not only establish La3MgBi5 as a suitable platform to study AHE and quantum transport but also indicate the great potential of 315-type Bi-based materials for exploring novel physical properties.