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When faced with starvation, the bacterium Bacillus subtilis transforms itself into a dormant cell type called a "spore". Sporulation initiates with an asymmetric division event, which requires the relocation of the core divisome components FtsA and FtsZ, after which the sigma factor σF is exclusively activated in the smaller daughter cell. Compartment-specific activation of σF requires the SpoIIE phosphatase, which displays a biased localization on one side of the asymmetric division septum and associates with the structural protein DivIVA, but the mechanism by which this preferential localization is achieved is unclear. Here, we isolated a variant of DivIVA that indiscriminately activates σF in both daughter cells due to promiscuous localization of SpoIIE, which was corrected by overproduction of FtsA and FtsZ. We propose that the core components of the redeployed cell division machinery drive the asymmetric localization of DivIVA and SpoIIE to trigger the initiation of the sporulation program.
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Bacillus subtilis , Proteínas de Bactérias , Bacillus subtilis/metabolismo , Ativação Transcricional , Proteínas de Bactérias/metabolismo , Esporos Bacterianos/genética , Esporos Bacterianos/metabolismo , Divisão Celular/genética , Fator sigma/genética , Fator sigma/metabolismoRESUMO
Menin inhibitors that disrupt Menin-MLL interaction hold promise for treating specific acute myeloid leukemia subtypes, including KMT2A rearrangements (KMT2A-r), yet resistance remains a challenge. Here, through systematic chromatin-focused CRISPR screens, along with genetic, epigenetic, and pharmacologic studies in a variety of human and mouse KMT2A-r AML models, we uncover a potential resistance mechanism independent of canonical Menin-MLL targets. We show that a group of non-canonical Menin targets, which are bivalently co-occupied by active Menin and repressive H2AK119ub marks, are typically downregulated following Menin inhibition. The loss of Polycomb Repressive Complex 1.1 (PRC1.1) subunits, such as PCGF1 or BCOR, leads to Menin inhibitor resistance by epigenetic reactivation of these non-canonical targets, including MYC. Genetic and pharmacological inhibition of MYC can resensitize PRC1.1-deficent leukemia cells to Menin inhibition. Moreover, we demonstrate that leukemia cells with the loss of PRC1.1 subunits exhibit reduced monocytic gene signatures and are susceptible to the BCL2 inhibition, and combinational treatment of venetoclax overcomes the resistance to Menin inhibition in PRC1.1-deficient leukemia cells. These findings highlight the important roles of PRC1.1 and its regulated non-canonical Menin targets in modulating Menin inhibitor response and provide potential strategies to treat leukemias with compromised PRC1.1 function.
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Tristetraprolin (TTP; also known as NUP475, GOS24, or TIS11), encoded by Zfp36, is an RNA-binding protein that regulates target gene expression by promoting mRNA decay and preventing translation. Although previous studies have indicated that TTP deficiency is associated with systemic inflammation and a catabolic-like skeletal phenotype, the mechanistic underpinnings remain unclear. Here, using both TTP-deficient (TTPKO) and myeloid-specific TTPKO (cTTPKO) mice, we reveal that global absence or loss of TTP in the myeloid compartment results in a reduced bone microarchitecture, whereas gain-of-function TTP knock-in (TTPKI) mice exhibit no significant loss of bone microarchitecture. Flow cytometry analysis revealed a significant immunosuppressive immune cell phenotype with increased monocytic myeloid-derived suppressor cells (M-MDSCs) in TTPKO and cTTPKO mice, whereas no significant changes were observed in TTPKI mice. Single-cell transcriptomic analyses of bone marrow myeloid progenitor cell populations indicated a dramatic increase in early MDSC marker genes for both cTTPKO and TTPKO bone marrow populations. Consistent with these phenotypic and transcriptomic data, in vitro osteoclastogenesis analysis of bone marrow M-MDSCs from cTTPKO and TTPKO displayed enhanced osteoclast differentiation and functional capacity. Focused transcriptomic analyses of differentiated M-MDSCs showed increased osteoclast-specific transcription factors and cell fusion gene expression. Finally, functional data showed that M-MDSCs from TTP loss-of-function mice were capable of osteoclastogenesis and bone resorption in a context-dependent manner. Collectively, these findings indicate that TTP plays a central role in regulating osteoclastogenesis through multiple mechanisms, including induction of M-MDSCs that appear to regulate skeletal phenotype.
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Células Supressoras Mieloides , Tristetraprolina , Animais , Camundongos , Osteoclastos/metabolismo , Osteogênese , Fenótipo , Tristetraprolina/genéticaRESUMO
BACKGROUND: Hypertrophic scar (HTS) is a prevalent chronic inflammatory skin disorder characterized by abnormal proliferation and extracellular matrix deposition and the precise mechanisms underlying HTS remain elusive. This study aimed to identify and validate potential immune-related genes associated with hypertrophic scar formation. METHODS: Skin samples from normal (n = 12) and hypertrophic scar tissues (n = 12) were subjected to RNA-seq analysis. Differentially expressed genes (DEGs) and significant modular genes in Weighted gene Co-expression Network Analysis (WGCNA) were identified. Subsequently, functional enrichment analysis was performed on the intersecting genes. Additionally, eight immune-related genes were matched from the ImmPort database. Validation of NRG1 and CRLF1 was carried out using an external cohort (GSE136906). Furthermore, the association between these two genes and immune cells was assessed by Spearman correlation analysis. Finally, RNA was extracted from normal and hypertrophic scar samples, and RT-qPCR, Immunohistochemistry staining and Western Blot were employed to validate the expression of characteristic genes. RESULTS: A total of 940 DEGs were identified between HTS and normal samples, and 288 key module genes were uncovered via WGCNA. Enrichment analysis in key module revealed involvement in many immune-related pathways, such as Th17 cell differentiation, antigen processing and presentation and B cell receptor signaling pathway. The eight immune-related genes (IFI30, NR2F2, NRG1, ESM1, NFATC2, CRLF1, COLEC12 and IL6) were identified by matching from the ImmPort database. Notably, we observed that activated mast cell positively correlated with CRLF1 expression, while CD8 T cells exhibited a positive correlation with NRG1. The expression of NRG1 and CRLF1 was further validated in clinical samples. CONCLUSION: In this study, two key immune-related genes (CRLF1 and NRG1) were identified as characteristic genes associated with HTS. These findings provide valuable insights into the immune-related mechanisms underlying hypertrophic scar formation.
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Cicatriz Hipertrófica , Neuregulina-1 , Receptores de Citocinas , Humanos , Diferenciação Celular , Cicatriz Hipertrófica/genética , Bases de Dados Factuais , Matriz Extracelular , Pele , Receptores de Citocinas/genéticaRESUMO
BACKGROUND: Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis (RA) and is associated with a poor prognosis. However, the role of blood biomarkers in RA-associated interstitial lung disease (RA-ILD) is ill-defined. We aim to evaluate the role of YKL-40 and Krebs von den Lungen-6 (KL-6) in the diagnosis and severity evaluation of RA-ILD. METHODS: 45 RA-non-ILD patients and 38 RA-ILD patients were included. The clinical data and the levels of YKL-40 and KL-6 were measured and collected for all patients. The risk factors for RA-ILD were analyzed and their correlation with relevant indicators and predictive value for RA-ILD was explored. RESULTS: The levels of YKL-40 and KL-6 in RA-ILD patients were higher than RA-non-ILD patients (p < .001). Both YKL-40 and KL-6 were correlated with the incidence of RA-ILD. The predictive power of combined KL-6 and YKL-40 for the presence of ILD was 0.789, with a sensitivity and specificity at 73.7% and 73.3%, respectively. In RA-ILD patients, both YKL-40 and KL-6 were positively correlated with the Scleroderma Lung Study (SLS) I score and negatively correlated with pulmonary function. CONCLUSIONS: KL-6 and YKL-40 might be a useful biomarker in the diagnosis and severity evaluation of RA-ILD.
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PURPOSE: Aging contributes significantly to cardiovascular diseases and cardiac dysfunction, leading to the upregulation of matrix metalloproteinase-9 (MMP-9) in the heart and a significant decrease in hydrogen sulfide (H2S) content, coupled with impaired cardiac diastolic function. This study explores whether supplementing exogenous hydrogen sulfide during aging ameliorates the decline in H2S concentration in the heart, suppresses MMP-9 expression, and improves the age-associated impairment in cardiac morphology and function. METHODS: We collected plasma from healthy individuals of different ages to determine the relationship between aging and H2S and MMP-9 levels through Elisa detection and liquid chromatography-tandem mass spectrometry (LC/MC) detection of plasma H2S content. Three-month-old mice were selected as the young group, while 18-month-old mice were selected as the old group, and sodium hydrosulfide (NaHS) was injected intraperitoneally from 15 months old until 18 months old as the old + NaHS group. Plasma MMP-9 content was detected using Elisa, plasma H2S content, cardiac H2S content, and cystathionine gamma-lyase (CSE) activity were detected using LC/MC, and cardiac function was detected using echocardiography. Heart structure was assessed using hematoxylin and eosin staining, Masone staining was used to detect the degree of cardiac fibrosis, while western blot was used to detect the expression of MMP-9, CSE, and aging marker proteins. Knockdown of MMP-9 and CSE in H9c2 cells using small interfering RNA was carried out to determine the upstream-downstream relationship between MMP-9 and CSE. RESULTS: H2S content in the plasma of healthy individuals decreases with escalating age, whereas MMP-9 level rises with age progression. Aging leads to a decrease in H2S levels in the heart and plasma of mice, severe impairment of cardiac diastolic function, interstitial relaxation, and fibrosis of the heart. Supplementing with exogenous H2S can improve these phenomena. CONCLUSION: H2S maintains the structure and function of the heart by inhibiting the expression of MMP-9 during the aging process.
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BACKGROUND: In several situations, spurious results are observed in the use of hematology analyzers including pseudothrombocytosis caused by part of the cytoplasm of abnormal cells which was reported in leukemic blasts, monoblasts, or lymphoblasts. METHODS AND RESULTS: Here, we report a rare case of pseudothrombocytosis caused by mature leukocyte fragments associated with heatstroke. It was identified by the peripheral blood smear and obvious difference between the PLT-F (fluorescence) and I (impedance) channel. CONCLUSIONS: Observation of peripheral blood smears and determination on the PLT-F channel can identify this interference caused by leukocyte fragments in heatstroke.
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Plaquetas , Golpe de Calor , Humanos , Contagem de Plaquetas/métodos , Leucócitos , Citoplasma , Golpe de Calor/complicações , Golpe de Calor/diagnósticoRESUMO
Hair follicle (HF) regeneration during wound healing continues to present a significant clinical challenge. Dermal papilla cell-derived exosomes (DPC-Exos) hold immense potential for inducing HF neogenesis. However, the accurate role and underlying mechanisms of DPC-Exos in HF regeneration in wound healing remain to be fully explained. This study, represents the first analysis into the effects of DPC-Exos on fibroblasts during wound healing. Our findings demonstrated that DPC-Exos could stimulate the proliferation and migration of fibroblasts, more importantly, enhance the hair-inducing capacity of fibroblasts. Fibroblasts treated with DPC-Exos were capable of inducing HF neogenesis in nude mice when combined with neonatal mice epidermal cells. In addition, DPC-Exos accelerated wound re-epithelialization and promoted HF regeneration during the healing process. Treatment with DPC-Exos led to increased expression levels of the Wnt pathway transcription factors ß-catenin and Lef1 in both fibroblasts and the dermis of skin wounds. Specifically, the application of a Wnt pathway inhibitor reduced the effects of DPC-Exos on fibroblasts and wound healing. Accordingly, these results offer evidence that DPC-Exos promote HF regeneration during wound healing by enhancing the hair-inducing capacity of fibroblasts and activating the Wnt/ß-catenin signaling pathway. This suggests that DPC-Exos may represent a promising therapeutic strategy for achieving regenerative wound healing.
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Proliferação de Células , Exossomos , Fibroblastos , Folículo Piloso , Camundongos Nus , Regeneração , Vibrissas , Via de Sinalização Wnt , Cicatrização , beta Catenina , Animais , Camundongos , Fibroblastos/metabolismo , Exossomos/metabolismo , Vibrissas/fisiologia , beta Catenina/metabolismo , Derme/metabolismo , Movimento Celular , Fator 1 de Ligação ao Facilitador Linfoide/metabolismoRESUMO
OBJECTIVE: This study assesses the relationship between adverse childhood experiences (ACE) occurring before the age of 18 years and patterns of fast-food consumption and sugary beverage consumption in adulthood. The study also examines how perceived stress and socio-economic status (SES) (college educational attainment and income) in adulthood mediate this relationship. DESIGN: Using data from the National Longitudinal Study of Adolescent to Adulthood Health (N 8599), multinomial logistic regression analyses were carried out to assess the association between ACE and unhealthy dietary behaviours in adulthood. Karlson-Holm-Breen mediation analysis is used to determine the mediating effects of SES and perceived stress. SETTING: Persons living in the USA in 2016-2018. PARTICIPANTS: Adults (n 8599) aged 33-44 years. RESULTS: The findings show an association between four or more ACE and high fast-food (relative risk ratio (RRR) = 1·436, 95 % CI = 1·040, 1·983) and high sugary beverage consumption (RRR = 1·435, 95 % CI = 1·002, 2·055). The association between ACE and high fast-food consumption is partially mediated by college educational attainment, and the association between ACE and high sugary beverage consumption is partially mediated by perceived stress and college educational attainment. CONCLUSIONS: ACE can have long-term consequences for unhealthy dietary behaviours in adulthood, and this relationship is partially due to a lower likelihood of higher perceived stress and college educational attainment among ACE-exposed persons. Future research is needed to understand further the influence of ACE on dietary patterns over the life course.
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Experiências Adversas da Infância , Adulto , Adolescente , Humanos , Estudos Longitudinais , Dieta , Classe Social , EscolaridadeRESUMO
Glioblastoma (GBM) is the most prevalent primary intracranial tumor. Temozolomide (TMZ) is the first-line chemotherapy for GBM. Nonetheless, the development of TMZ resistance has become a main cause of treatment failure in GBM patients. Evidence suggests that neuropilin-1 (NRP-1) silencing can attenuate GBM cell resistance to TMZ. This study aims to determine potential mechanisms by which NRP-1 affects TMZ resistance in GBM. The parental U251 and LN229 GBM cells were exposed to increasing concentrations of TMZ to construct TMZ-resistant GBM cells (U251/TMZ, LN229/TMZ). BALB/c nude mice were injected with U251/TMZ cells to establish the xenograft mouse model. Functional experiments were carried out to examine NRP-1 functions. Western blotting and real-time quantitative polymerase chain reaction were used to evaluate molecular protein and mRNA expression, respectively. Immunohistochemical staining showed NRP-1 and STAT1 expression in mouse tumors. The results showed that NRP-1 was highly expressed in TMZ-resistant cells. Moreover, knocking down NRP-1 attenuated the TMZ resistance of U251/TMZ cells, while upregulating NRP-1 enhanced TMZ resistance of the parental cells. NRP-1 silencing elevated GBM cell sensitivity to TMZ in tumor-bearing mice. Depleting NRP-1 reduced STAT1, p53, and p21 expression in U251/TMZ cells. STAT1 depletion offset NRP-1 silencing evoked attenuation of GBM cell resistance to TMZ. Collectively, our study reveals that NRP-1 enhances TMZ resistance in GBM possibly by regulating the STAT1/p53/p21 axis.
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Antineoplásicos Alquilantes , Neoplasias Encefálicas , Resistencia a Medicamentos Antineoplásicos , Glioblastoma , Camundongos Endogâmicos BALB C , Camundongos Nus , Neuropilina-1 , Fator de Transcrição STAT1 , Temozolomida , Proteína Supressora de Tumor p53 , Temozolomida/farmacologia , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/genética , Animais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neuropilina-1/metabolismo , Neuropilina-1/genética , Humanos , Fator de Transcrição STAT1/metabolismo , Antineoplásicos Alquilantes/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Linhagem Celular Tumoral , Camundongos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Asparagus officinalis has a homologous value in medicine and vegetables. Its immature stem, commonly called asparagus, is a central edible part. Asparagus skin and leaf also contain rich nutrients. However, these parts are often discarded. This study investigated amino acid and mineral elements in immature stem, skinless asparagus, asparagus skin, and leaf. Their quality was further evaluated by chemometrics methods such as principal component analysis and neural network analysis. The results showed amino acid content was high in immature stem and skinless asparagus and low in leaf, whereas the mineral elements were in four parts. Quality evaluation results showed four parts were divided into three grades. Immature stem and skinless asparagus were grouped into cluster 1 with the best quality as high-quality raw materials in food and health-care products. Meanwhile, three AA (Cys, His, Arg) and two mineral elements (Na, Cr) were identified as quality evaluation iconic substances.
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Asparagus , Asparagus/química , Aminoácidos , Quimiometria , Minerais , Verduras/químicaRESUMO
Dragon's blood (DB) is a traditional Chinese medicine (TCM) with hemostatic effects and antibacterial properties. However, it is still challenging to use for rapid hemostasis because of its insolubility. In this study, different amounts of DB were loaded on mesoporous silica nanoparticles (MSNs) to prepare a series of DB-MSN composites (5DB-MSN, 10DB-MSN, and 20DB-MSN). DB-MSN could quickly release DB and activate the intrinsic blood coagulation cascade simultaneously by DB and MSN. Hemostasis tests demonstrated that DB-MSN showed superior hemostatic effects than either DB or MSNs alone, and 10DB-MSN exhibited the best hemostatic effect. In addition, the antibacterial activities of DB-MSN against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) improved with the increase in DB. Furthermore, the hemolysis assay and cytocompatibility assay demonstrated that all DB-MSNs exhibited excellent biocompatibility. Based on these results, 10DB-MSN is expected to have potential applications for emergency hemostatic and antibacterial treatment in pre-hospital trauma.
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Antibacterianos , Escherichia coli , Hemostasia , Hemostáticos , Nanopartículas , Extratos Vegetais , Dióxido de Silício , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/química , Dióxido de Silício/química , Nanopartículas/química , Escherichia coli/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Hemostáticos/química , Hemostáticos/farmacologia , Porosidade , Animais , Hemólise/efeitos dos fármacos , Coagulação Sanguínea/efeitos dos fármacos , Humanos , Dracaena/química , Camundongos , Testes de Sensibilidade MicrobianaRESUMO
There are three main classes of actin nucleation factors: Arp2/3 complexes, Spire and Formin. Spire assembles microfilaments by nucleating stable longitudinal tetramers and binding actin to the growing end of the microfilament. As early as 1999, Wellington et al. identified Spire as an actin nucleating agent, however, over the years, most studies have focused on Arp2/3 and Formin proteins; there has been relatively less research on Spire as a member of the actin nucleating factors. Recent studies have shown that Spire is involved in the vesicular transport through the synthesis of actin and plays an important role in neural development. In this paper, we reviewed the structure, expression and function of Spire, and its association with disease in order to identify meaningful potential directions for studies on Spire.
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Actinas , Proteínas dos Microfilamentos , Proteínas Nucleares , Proteínas dos Microfilamentos/metabolismo , Proteínas dos Microfilamentos/fisiologia , Humanos , Animais , Actinas/metabolismo , Actinas/fisiologia , Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/fisiologiaRESUMO
Introduction: This study aimed to explore the correlation of systemic immune-inflammation index (SII) and prognostic nutritional index (PNI) with the recurrence and prognosis in patients with advanced oral squamous cell carcinoma (OSCC). Methods: A total of 298 OSCC patients with the stage of III/IV were finally included in the study. SII = neutrophil count (109/L) × platelet count (109/L)/lymphocyte count (109/L). PNI = serum albumin (g/L) + 5 × total lymphocyte count (109/L). Results: High preoperative SII and low preoperative PNI were independent risk factors for tumor recurrence in OSCC patients of the stage of III/IV. The area under the curves (AUC) for SII was 0.69 (0.63 to 0.76), for PNI was 0.72 (0.67 to 0.78), and for joint model was 0.81 (0.76 to 0.85). Patients with low level of joint model had significantly higher overall survival rate for 5 years follow-up than those with high level. Discussion: Both preoperative SII and PNI are valuable independent tumor recurrence prediction index in patients with advanced OSCC. Meanwhile, the combination of preoperative SII and PNI is also valuable on OSCC recurrence and prognosis prediction.
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BACKGROUND: Diabetic nephropathy (DN) is a severe diabetic complication disorder. Circular RNAs (circRNAs) actively participate in DN pathogenesis. In this report, we sought to define a new mechanism of circ_0003928 in regulating high glucose (HG)-induced HK-2 cells. METHODS: To construct a DN cell model, we treated HK-2 cells with HG. Cell viability and apoptosis were detected by CCK-8 and flow cytometry, respectively. The inflammatory cytokines were quantified by ELISA. Protein analysis was performed by immunoblotting, and mRNA expression was detected by quantitative PCR. The circ_0003928/miR-31-5p and miR-31-5p/MAPK6 relationships were validated by RNA pull-down and luciferase assays. RESULTS: HG promoted HK-2 cell apoptosis, fibrosis and oxidative stress. Circ_0003928 and MAPK6 levels were enhanced and miR-31-5p level was decreased in HK-2 cells after HG treatment. Circ_0003928 disruption promoted cell growth and inhibited apoptosis, inflammatory response, fibrosis and oxidative stress in HG-induced HK-2 cells. Circ_0003928 targeted miR-31-5p, and MAPK6 was a target of miR-31-5p. Circ_0003928 regulated MAPK6 expression through miR-31-5p. The functions of circ_0003928 disruption in HG-induced HK-2 cells were reversed by miR-31-5p downregulation or MAPK6 upregulation. CONCLUSION: Circ_0003928 exerts regulatory impacts on HG-induced apoptosis, inflammation, fibrosis and oxidative stress in human HK-2 cells by the miR-31-5p/MAPK6 axis.
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The mental health (MH) of older adults is a prominent public health concern. However, research regarding the impact of emerging Internet use on MH among older adults remains limited, particularly in transitional economies experiencing a rapidly aging population such as China. Thus, to address this research gap, this study uses data from the 2013-2018 waves of the China Health and Retirement Longitudinal Study. To investigate the causal relationship between Internet use and MH among older adults and explore the underlying channels through which this relationship operates. The results reveal a notable positive association between Internet use and MH among older adults. Furthermore, the study highlights social interaction, social trust, traveling expenses, and healthy habits as crucial channels through which Internet use can impact MH among older adults. The analysis also reveals how Internet use demonstrates a stronger positive effect on older individuals who have fewer chronic diseases and live with their offspring compared with their counterparts. These findings have significant policy implications, which thus emphasizes the need to enhance Internet use among older adults as a means of improving their MH.
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Anoxygenic phototrophic bacteria is a promising catalyst for constructing bioanode, but the mixed culture with non-photosynthetic bacteria is inevitable in an open environment application. In this study, a Rhodopseudomonas-dominated mixed culture with other electrogenic bacteria was investigated for deciphering the differentiated performance on electricity generation in light or dark conditions. The kinetic study showed that reaction rate of OM degradation was 9 times higher than that under dark condition, demonstrating that OM degradation was enhanced by photosynthesis. However, CE under light condition was lower. It indicated that part of OM was used to provide hydrogen donors for the fixation of CO2 or hydrogen production in photosynthesis, decreasing the OM used for electron transfer. In addition, higher COD concentration was not conducive to electricity generation. EIS analysis demonstrated that higher OM concentration would increase Rct to hinder the transfer of electrons from bacteria to the electrode. Indirect and direct electron transfer were revealed by CV analysis for light and dark biofilm, respectively, and nanowires were also observed by SEM graphs, further revealing the differentiate performance. Microbial community analysis demonstrated Rhodopseudomonas was dominated in light and decreased in dark, but Geobacter increased apparently from light to dark, resulting in different power generation performance. The findings revealed the differentiated performance on electricity generation and pollutant removal by mixed culture of phototrophic bacteria in light or dark, which will improve the power generation from photo-microbial fuel cells.
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Fontes de Energia Bioelétrica , Eletricidade , Rodopseudomonas , Rodopseudomonas/metabolismo , Fotossíntese , Luz , Eletrodos , Biofilmes/crescimento & desenvolvimento , Análise da Demanda Biológica de Oxigênio , Transporte de Elétrons , Geobacter/metabolismo , Geobacter/fisiologiaRESUMO
The study of myeloid-derived suppressor cells (MDSCs) has been commonly reported in the context of cancer immunology. MDSCs play a key role in cancer growth and progression by inhibiting both innate and adaptive immunity. In addition to the immunosuppressive function of MDSCs in cancer, a novel function of MDSCs as osteoclast precursors has recently been attracting attention. Because monocytic-MDSCs (M-MDSCs) are derived from the same myeloid lineage as macrophages, which are osteoclast progenitors, M-MDSCs can undergo differentiation into osteoclasts, contributing to bone destruction not only in the cancer microenvironment but also in inflammatory conditions including obesity and osteoarthritis. Herein, we present details of the technique to evaluate osteoclasts in vitro, as well as specific techniques to isolate M-MDSCs and identify them. This protocol can be easily adapted to isolate M-MDSCs from most pathologic conditions for easy evaluation.
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Células Supressoras Mieloides , Neoplasias , Animais , Camundongos , Osteogênese , Microambiente TumoralRESUMO
Protein amyloid fibrillation is linked to a wide range of neurodegenerative diseases. Protein oligomer is an intermediate substance in the process of fibrillation, which is neurotoxic and formed by the aggregation of protein molecules under physiological stress. Early detection of protein oligomers could make timely intervention of protein fibrillation related diseases. Therefore, it is crucial to develop efficient inhibitors and probes for monitoring amyloid fibril formation. In this study, we developed a novel amyloid inhibitor quinoline yellow (QY), which was proved to be effective in inhibiting insulin protein fibrillation as demonstrated by fluorescence, morphology characterization and circular dichroism. When QY binds to insulin, it exerts inhibitory effects on the nucleation process and effectively impedes the formation of fibrillar fibrils. In addition, we present the application of surface-enhanced Raman spectroscopy (SERS) as an extremely sensitive technique for identifying amyloid oligomers. The investigation employed the probe QY, which demonstrated a linear reaction for identifying oligomers in the concentration range of 1.0-58.0 µM. Impressively, it showcased an exceptionally sensitive detection threshold of 0.2 µM. And also illustrating the binding sites and interaction mechanisms between small molecules of QY and insulin by SERS. The aforementioned methodology was also employed for the identification of insulin oligomers in human serum samples. Thereby, the proposed approach presenting a promising avenue with extensive implications in the realms of pharmaceutical exploration and disease diagnosis.
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OBJECTIVE: To analyze the effects of Huoxue Qufeng Decoction combined with Tongguan Liquefying Acupoint Penetration therapy on swallowing function and quality of life in patients with ischemic stroke. METHODS: A total of 145 patients with post-stroke dysphagia admitted to Dingxi People's Hospital from January 2019 to May 2022 were selected with 65 patients in the control group and 80 patients in the observation group. The control group received Huoxue Qufeng Decoction alone, while the observation group received additional Tongguan Liquefying Acupoint Penetration therapy. Clinical efficacy, NIH Stroke Scale (NIHSS) score, Water Swallow Test, Swallowing Function Assessment (SSA) score, MD Anderson Dysphagia Inventory (MDADI) score, overall incidence of adverse events, and Swallowing Quality of Life (SWAL-QOL) score were compared between the two groups. RESULTS: The total response rate in the observation group was higher than that in the control group, with a statistically significant difference (P<0.01). After treatment, the SSA score and NIHSS score were statistically lower in the observation group than in the control group (P<0.01). The MDADI and SWAL-QOL scores were higher in the observation group than in the control group, with a statistically significant difference (both P<0.01). The total effective rate reflected by the Water Swallow Test was significantly higher in the observation group than in the control group (P<0.05). There was no significant difference in the incidence of adverse events between the two groups (P>0.05). Univariate analysis revealed that age and treatment plan were factors influencing the recovery of swallowing function. Logistic multivariate regression analysis further identified age and treatment plan as independent risk factors affecting patient prognosis (P<0.05). CONCLUSION: Huoxue Qufeng Decoction combined with Tongguan Liquefying Acupoint Penetration has a significant effect on post-stroke dysphagia, effectively improving swallowing function and enhancing quality of life.