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Although targeted therapy has revolutionized oncotherapy, engineering a versatile oncotherapy nanoplatform integrating both diagnostics and therapeutics has always been an intractable challenge to overcome the limitations of monotherapy. Herein, a theranostics platform based on DI/MP-MB has successfully realized the fluorescence detection of disease marker miR-21 and the gene/photothermal/chemo triple synergetic cancer therapy, which can trace the tumor through photothermal and fluorescence dual-mode imaging and overcome the limitations of monotherapy to improve the treatment efficiency of tumors. DI/MP-MB was prepared by magnetic mesoporous silicon nanoparticles (M-MSNs) loaded with doxorubicin (Dox) and new indocyanine green (IR820), and subsequently coating polydopamine as a "gatekeeper", followed by the surface adsorbed with molecular beacons capable of targeting miR-21 for responsive imaging. Under the action of enhanced permeability retention and external magnetic field, DI/MP-MB were targeted and selectively accumulated in the tumor. MiR-21 MB hybridized with miR-21 to form a double strand, which led to the desorption of miR-21 MB from the polydopamine surface and the fluorescence recovery to realize gene silencing and fluorescence imaging for tracking the treatment process. Meanwhile, with the response to the near-infrared irradiation and the tumor's microacid environment, the outer layer polydopamine will decompose, releasing Dox and IR820 to realize chemotherapy and photothermal therapy. Finally, the ability of DI/MP-MB to efficiently suppress tumor growth was comprehensively assessed and validated both in vitro and in vivo. Noteworthily, the excellent anticancer efficiency by the synergistic effect of gene/photothermal/chemo triple therapy of DI/MP-MB makes it an ideal nanoplatform for tumor therapy and imaging.
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Polycystic ovary syndrome (PCOS), which is the most prevalent endocrine disorder among women in their reproductive years, is linked to a higher occurrence and severity of atherosclerosis (AS). Nevertheless, the precise manner in which PCOS impacts the cardiovascular well-being of women remains ambiguous. The Gene Expression Omnibus database provided four PCOS datasets and two AS datasets for this study. Through the examination of genes originating from differentially expressed (DEGs) and critical modules utilizing functional enrichment analyses, weighted gene co-expression network (WGCNA), and machine learning algorithm, the research attempted to discover potential diagnostic genes. Additionally, the study investigated immune infiltration and conducted gene set enrichment analysis (GSEA) to examine the potential mechanism of the simultaneous occurrence of PCOS and AS. Two verification datasets and cell experiments were performed to assess biomarkers' reliability. The PCOS group identified 53 genes and AS group identified 175 genes by intersecting DEGs and key modules of WGCNA. Then, 18 genes from two groups were analyzed by machine learning algorithm. Death Associated Protein Kinase 1 (DAPK1) was recognized as an essential gene. Immune infiltration and single-gene GSEA results suggest that DAPK1 is associated with T cell-mediated immune responses. The mRNA expression of DAPK1 was upregulated in ox-LDL stimulated RAW264.7 cells and in granulosa cells. Our research discovered the close association between AS and PCOS, and identified DAPK1 as a crucial diagnostic biomarker for AS in PCOS.
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Aterosclerosis , Síndrome del Ovario Poliquístico , Síndrome del Ovario Poliquístico/genética , Femenino , Humanos , Aterosclerosis/genética , Ratones , Animales , Redes Reguladoras de Genes , Perfilación de la Expresión Génica , Células RAW 264.7 , Aprendizaje Automático , Células de la Granulosa/metabolismo , BiomarcadoresRESUMEN
Previous retrospective cohort studies have found that, compared with oxygen tension in the uterus and fallopian tubes (2â¯%-8â¯%), exposure of pre-implantation embryos to atmospheric oxygen tension (AtmO2, 20â¯%) during assisted reproductive technology(ART) can affect embryo quality, pregnancy outcomes and offspring health. However, current research on the effects and mechanisms of AtmO2 on the development of embryos and offspring is mainly limited to animal experiments. Human embryonic stem cells (hESCs) play a special and irreplaceable role in the study of early human embryonic development. In this study, we used hESCs as a model to elucidate the possible effects and mechanisms of AtmO2 exposure on human embryonic development. We found that exposure to AtmO2 can reduce cell viability, produce oxidative stress, increase DNA damage, initiate DNA repair, activate autophagy, and increase cell apoptosis. We also noticed that approximately 50â¯% of hESCs survived, adapted and proliferated through high expression of self-renewal and pluripotency regulatory factors, and affected embryoid body differentiation. These data indicate that hESCs experience oxidative stress, accumulation of DNA damage, and activate DNA damage response under the selective pressure of AtmO2.Some hESCs undergo cell death, whereas other hESCs adapt and proliferate through increased expression of self-renewal genes. The current findings provide in vitro evidence that exposure to AtmO2 during the early preimplantation stage negatively affects hESCs.
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A target-triggered strand displacement-assisted target recycling based on carbon dots-based fluorescent probe and mesoporous silica nanoparticles@polydopamine (MSNs@PDA) was established to detect miRNA. The surface of MSNs rich in mesopores was coated with a layer of PDA, which can adsorb and quench the fluorescence of single-stranded Fuel DNA with fluorescent carbon dots (CDs) modified at the end through fluorescence resonance energy transfer (FRET). After adding double-stranded DNA-gold nanoparticles (dsDNA-AuNPs) and target let-7a, it will trigger two toehold-mediated strand displacement reactions (TSDR), leading to the recovery of fluorescence and the recycling of target let-7a (excitation wavelength: 380 nm; emission wavelength: 458 nm). The recovery value of fluorescence is proportional to the logarithm of the target microRNA let-7a concentration, thus realizing the sensitivity amplification detection of disease markers. The MSNs@PDA@Fuel DNA-CDs/dsDNA-AuNPs nanoplatform based on the strategy of "on-off-on" and TSDR cyclic amplification may hold great potential as an effective and safe nanoprobe for accurate fluorescence imaging of diseases related to miRNA with low abundances.
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Carbono , Colorantes Fluorescentes , Oro , Indoles , MicroARNs , Polímeros , Puntos Cuánticos , Dióxido de Silicio , MicroARNs/análisis , Colorantes Fluorescentes/química , Carbono/química , Humanos , Puntos Cuánticos/química , Polímeros/química , Oro/química , Dióxido de Silicio/química , Indoles/química , Transferencia Resonante de Energía de Fluorescencia/métodos , Nanopartículas del Metal/química , Imagen Óptica/métodos , Límite de Detección , Porosidad , ADN/químicaRESUMEN
Introduction: Fruit size is an important economic trait affecting jujube fruit quality, which has always been the focus of marker-assisted breeding of jujube traits. However, despite a large number of studies have been carried out, the mechanism and key genes regulating jujube fruit size are mostly unknown. Methods: In this study, we used a new analysis method Quantitative Trait Loci sequencing (QTL-seq) (bulked segregant analysis) to screen the parents 'Yuhong' and 'Jiaocheng 5' with significant phenotypic differences and mixed offspring group with extreme traits of large fruit and small fruit, respectively, and, then, DNA mixed pool sequencing was carried out to further shortening the QTL candidate interval for fruit size trait and excavated candidate genes for controlling fruit size. Results: The candidate intervals related to jujube fruit size were mainly located on chromosomes 1, 5, and 10, and the frequency of chromosome 1 was the highest. Based on the QTL-seq results, the annotation results of ANNOVAR were extracted from 424 SNPs (single-nucleotide polymorphisms) and 164 InDels (insertion-deletion), from which 40 candidate genes were selected, and 37 annotated candidate genes were found in the jujube genome. Four genes (LOC107428904, LOC107415626, LOC125420708, and LOC107418290) that are associated with fruit size growth and development were identified by functional annotation of the genes in NCBI (National Center for Biotechnology Information). The genes can provide a basis for further exploration and identification on genes regulating jujube fruit size. Discussion: In summary, the data obtained in this study revealed that QTL intervals and candidate genes for fruit size at the genomic level provide valuable resources for future functional studies and jujube breeding.
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The scroll paintings for ancestor trees have been used to inherit the spirit of ancestor worship as a historical record of family development since the late Ming Dynasty in China. A severely degraded scroll painting of an ancestor tree (made of cotton textiles) needs intervention and conservation treatment to mitigate further deterioration. On the basis of the previously reported characterization results for the painting, in this paper, a suspension that is composed of 0.6% cellulose nanofibril (CNF) and nanosized 0.15% MgO in aqueous solvent (denoted as the CNF-MgO susairpension) was prepared. Conventional characterization methods were used to assess the properties of model samples before and after treatment with the CNF-MgO suspension, as well as before and after degradation under two sets of conditions. The results show that the treated model samples are slightly alkaline, given the deposit of alkaline particles, and demonstrate good mechanical properties before and after degradation due to the increase in fiber-to-fiber bond and mitigation of acid-catalyzed hydrolysis. In spite of the non-transparency of CNF and MgO nanoparticles, they have little impact on the optical properties of textiles, as verified by transmittance data and the determination of color changes. This suspension was then used to reinforce and restore the scroll painting in a practical conservation process. The application of CNF and MgO nanoparticles on textile objects investigated in this study would expand our understanding of the conservation of such objects, especially for those that have already become acidic and degraded.
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Trehalases (TREs) are pivotal enzymes involved in insect development and reproduction, making them prime targets for pest control. We investigated the inhibitory effect of three thiazolidinones with piperine skeletons (6a, 7b, and 7e) on TRE activity and assessed their impact on the growth and development of the fall armyworm (FAW), Spodoptera frugiperda. The compounds were injected into FAW larvae, while the control group was treated with 2% DMSO solvent. All three compounds effectively inhibited TRE activity, resulting in a significant extension of the pupal development stage. Moreover, the treated larvae exhibited significantly decreased survival rates and a higher incidence of abnormal phenotypes related to growth and development compared to the control group. These results suggest that these TRE inhibitors affect the molting of larvae by regulating the chitin metabolism pathway, ultimately reducing their survival rates. Consequently, these compounds hold potential as environmentally friendly insecticides.
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Alcaloides , Benzodioxoles , Insecticidas , Piperidinas , Alcamidas Poliinsaturadas , Trehalasa , Animales , Larva , Spodoptera , Trehalasa/genética , Insecticidas/farmacologíaRESUMEN
The durability of wooden heritage objects and sites can be affected by external environmental factors, leading to decay, cracking, and other forms of deterioration, which might ultimately result in significant and irreversible loss. In this study, a FEVE resin was modified with Ag2O/OH-MWCNTS (MA), denoted as MAF, where three concentrations were prepared using in situ precipitation, and the resulting composite adhesive was characterized by a high viscosity and effective bacteriostatic properties, demonstrating a better viscosity and thermal stability, as well as antibacterial properties, than pure FEVE resin. The results show that MAF adhesives present good thermal stability, as evidenced by a lower mass loss rate following treatment at 800 °C compared to the pure FEVE resin. At a consistent shear rate, the viscosity of MAF demonstrates a notable increase with the proportion of MA, which is better than that of FEVE. This suggests that the nano-Ag2O particles in MA act as physical crosslinking agents in FEVE, improving the viscosity of the composite adhesive MAF. The adhesion strength between MAF and wood exhibits a similar trend, with wooden samples showing higher shear strengths as the proportion of MA increases in comparison to FEVE. Simultaneously, the antibacterial effects of the MAF adhesive exceeded 1 mm for Trichoderma, Aspergillus niger, and white rot fungi. The antibacterial activity of the MAF adhesive exhibited a direct correlation with the concentration of Ag2O/OH-MWCNTS, with the most pronounced inhibitory effect observed on Trichoderma. The MAF adhesive demonstrates promising prospects as an adhesive for wooden heritage artifacts, offering a novel approach for the rapid, environmentally friendly, and efficient development of composite adhesives with superior adhesive properties.
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BACKGROUND: Previous studies have indicated bidirectional associations between urate levels and inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). However, it remains unclear whether the observations are causal because of confounding factors. AIM: To investigate the causal associations between urate levels and IBD using bidirectional Mendelian randomization (MR). METHODS: Independent genetic variants for urate levels and IBD were selected as instrumental variables from published genome-wide association studies (GWASs). Summary statistics for instrument-outcome associations were retrieved from three separate databases for IBD (the UK Biobank, the FinnGen database and a large GWAS meta-analysis) and one for urate levels (a large GWAS meta-analysis). MR analyses included the inverse-variance-weighted method, weighted-median estimator, MR-Egger and sensitivity analyses (MR-PRESSO). A meta-analysis was also conducted to merge the data from separate outcome databases using a fixed-effects model. RESULTS: Genetically higher serum urate levels were strongly associated with an increased risk of UC [odds ratio (OR): 1.95, 95% confidence interval (CI): 1.86-2.05] after outlier correction, and the ORs (95%CIs) for IBD and CD were 0.94 (95%CI: 0.86-1.03) and 0.91 (95%CI: 0.80-1.04), respectively. Animal studies have confirmed the positive association between urate levels and UC. Moreover, genetically predicted IBD was inversely related to urate levels (OR: 0.97, 95%CI: 0.94-0.99). However, no association was observed between genetically influenced UC or CD and urate levels. CONCLUSION: Urate levels might be risk factors for UC, whereas genetically predicted IBD was inversely associated with urate levels. These findings provide essential new insight for treating and preventing IBD.
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Our previous research suggests that targeting NLRP3 inflammasomes holds promise for mitigating cerebral ischemia/reperfusion injury. The gut metabolite Urolithin B (UroB) has been shown to inhibit the neuroinflammation. However, the specific role of UroB in cerebral ischemia/reperfusion injury and its potential impact on NLRP3 inflammasome remain unclear. In this study, acute stroke was simulated using the MCAO model in male Sprague-Dawley rats. UroB was intraperitoneally administered after 1 h of reperfusion. The effects of UroB on brain tissue were evaluated, including infarct volume, brain edema, and neurobehavioral changes. Western blotting and immunofluorescence were performed to investigate the effect of UroB on inflammation-related proteins. Furthermore, TRIM65 knockdown and TXNIP overexpression experiments elucidated the role of UroB in NLRP3 inflammasome activation. The ( demonstrate the neuroprotective effect of UroB in acute stroke, reducing brain tissue damage and improving motor function. Mechanistically, UroB modulated neuroinflammation by influencing TXNIP and TRIM65 protein expression, as well as competitive binding to the NLRP3 inflammasome, attenuating cerebral ischemia/reperfusion injury. In conclusion, the potential of UroB as a protective agent against cerebral ischemia/reperfusion injury in acute stroke stands out as it regulates TRIM65 and TXNIP competitive binding to the NLRP3 inflammasome. These findings suggest that UroB is a promising drug candidate for the treatment of acute stroke.
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Isquemia Encefálica , Cumarinas , Daño por Reperfusión , Accidente Cerebrovascular , Animales , Masculino , Ratas , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Proteínas de Ciclo Celular , Cumarinas/metabolismo , Cumarinas/farmacología , Cumarinas/uso terapéutico , Inflamasomas/metabolismo , Enfermedades Neuroinflamatorias , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismoRESUMEN
Wood-derived hydrogels possess satisfactory longitudinal strength but lack excellent swelling resistance and dry shrinkage resistance when achieving high anisotropy. In this study, we displayed the preparation of highly dimensional stable wood/polyacrylamide hydrogels (wood/PAM-Al3+). The alkali-treated wood retains lignin as the skeleton of the hydrogel. Second, Al ions were added to the metal coordination with lignin. Finally, by employing free radical polymerization, we construct a conductive electronic network using polyaniline within the wood/PAM-Al3+ matrix to create the flexible sensor. This approach leverages lignin's integrated structure within the middle lamella to provide enhanced swelling resistance and stronger binding strength in the transverse direction. Furthermore, coordination between lignin and Al ions improves the mechanical strength of the wood hydrogel. Polyaniline provides stable linear pressure and temperature responses. The wood/PAM-Al3+ exhibits a transverse swelling ratio of 3.90% while achieving a longitudinal tensile strength of 20.5 MPa. This high-strength and high-stability sensor is capable of monitoring macroscale human behavior. Therefore, this study presents a simple yet innovative strategy for constructing tough hydrogels while also establishing an alternative pathway for exploring lignin networks in new functional materials development.
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Compuestos de Anilina , Hidrogeles , Lignina , Humanos , Lignina/química , Hidrogeles/química , Madera , Iones/química , Conductividad EléctricaRESUMEN
Transcription factors within microglia contribute to the inflammatory response following intracerebral hemorrhage (ICH). Therefore, we employed bioinformatics screening to identify the potential transcription factor tonicity-responsive enhancer-binding protein (TonEBP) within microglia. Inflammatory stimuli can provoke an elevated expression of TonEBP in microglia. Nevertheless, the expression and function of microglial TonEBP in ICH-induced neuroinflammation remain ambiguous. In our recent research, we discovered that ICH instigated an increased TonEBP in microglia in both human and mouse peri-hematoma brain tissues. Furthermore, our results indicated that TonEBP knockdown mitigates lipopolysaccharide (LPS)-induced inflammation and the activation of NF-κB signaling in microglia. In order to more deeply comprehend the underlying molecular mechanisms of how TonEBP modulates the inflammatory response, we sequenced the transcriptomes of TonEBP-deficient cells and sought potential downstream target genes of TonEBP, such as Pellino-1 (PELI1). PELI has been previously reported to mediate nuclear factor-κB (NF-κB) signaling. Through the utilization of CUT & RUN, a dual-luciferase reporter, and qPCR, we confirmed that TonEBP is the transcription factor of Peli1, binding to the Peli1 promoter. In summary, TonEBP may enhance the LPS-induced inflammation and activation of NF-κB signaling via PELI1.
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Hemorragia Cerebral , Microglía , Factores de Transcripción NFATC , Animales , Humanos , Ratones , Hemorragia Cerebral/genética , Hemorragia Cerebral/metabolismo , Inflamación/genética , Inflamación/metabolismo , Lipopolisacáridos/toxicidad , Lipopolisacáridos/metabolismo , Microglía/metabolismo , Enfermedades Neuroinflamatorias , FN-kappa B/metabolismo , Factores de Transcripción NFATC/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
Transcranial electrical stimulation (TES) is a promising non-invasive neuromodulation technique. How to increase the current intensity entering the skull and reduce scalp shunting has become a key factor significantly influencing regulatory efficacy. In this study, we introduce a novel approach for optimizing TES by adjusting local scalp temperature to modulate scalp conductivity. We have developed simulation models for TES-induced electric fields and for temperature-induced alterations in scalp conductivity. Two common types of stimulation montage (M1-SO and 4 × 1 montage) were adopted for the evaluation of effectiveness. We observed that the modulation of scalp temperature has a significant impact on the distribution of the electric field within the brain during TES. As local scalp temperature decreases, there is an increase in the maximum electric field intensity within the target area, with the maximum change reaching 18.3%, when compared to the electric field distribution observed under normal scalp temperature conditions. Our study provide insights into the practical implementation challenges and future directions for this innovative methodology.
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Estimulación Transcraneal de Corriente Directa , Estimulación Transcraneal de Corriente Directa/métodos , Cuero Cabelludo , Temperatura , Encéfalo/fisiología , Conductividad Eléctrica , Estimulación EléctricaRESUMEN
Human milk is the best source of nutrition for infants. Lower freezing temperatures and faster freezing rates allow for better preservation of human milk. However, research on the freezing conditions of human milk is limited. This study investigated the effectiveness of quick freezing and suitable freezing conditions for home preservation. Human milk was stored under different freezing conditions (-18 °C, -18 °C quick freezing, -30 °C, -40 °C, -60 °C, and - 80 °C) for 30, 60, and 90 days and then evaluated for changes in the microbial counts, bioactive protein, and lipid. The results showed that the total aerobic bacterial and Bifidobacteria counts in human milk after storage at freezing temperatures of - 30 °C and lower were closer to those of fresh human milk compared to - 18 °C. Furthermore, the lysozyme loss, lipid hydrolysis degree, and volatile organic compound production were lower. However, -18 °C quick freezing storage was not markedly different from -18 °C in maintaining human milk quality. Based on the results, for household and environmental reasons, the recommended temperature for storing human milk is suggested as -30 °C.
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Frío , Leche Humana , Humanos , Congelación , Leche Humana/microbiología , Refrigeración , LípidosRESUMEN
BACKGROUND: Pain can have a serious impact on a patient's physical, mental, and social health, often causing their quality of life to decline. Various nicotine dosage forms, such as nicotine patches and nasal spray, have been developed and used as analgesics in clinical settings. However, there is controversy over the anti-nociceptive effects of nicotine among different clinical trials. The purpose of this meta-analysis is to quantify the analgesic effect of nicotine patches, nicotine nasal spray, and tobacco smoking on pain in humans. METHODS: Relevant articles published in English prior to July 2023 were identified using the PubMed, Cochrane Library, and Embase online databases in accordance with PRISMA (2020) guidelines. Two reviewers independently screened and selected studies, extracted data, and assessed the quality of the included studies using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). RStudio was used for data synthesis, heterogeneity assessment, sensitivity analysis, publication bias assessment, trim-and-fill analyses, and generating forest plots. RESULTS: Sixteen eligible articles, including k = 5 studies of pain tolerance (n = 210), k = 5 studies of pain threshold (n = 210), and k = 12 studies of pain scores (N = 1249), were included for meta-analysis. Meta-analytic integration for pain threshold (Hedges' g = 0.28, 95% CI = 0-0.55, Z = 1.99, p = 0.05) and pain tolerance (Hedges' g = 0.32, 95% CI = 0.05-0.59, Z = 2.30, p = 0.02) revealed that nicotine administered via tobacco smoke generated acute analgesic effects to thermal stimuli. Meta-analytic integration for pain scores revealed that nicotine had a weak anti-nociceptive effect on postoperative pain of -0.37 (95% CI = -0.77 to 0.03, Z = -1.80) but with no statistical significance (p = 0.07). In addition, a limited number of included studies revealed that long-term smoking produced hyperalgesia that may be characterized as small to medium in magnitude (Hedges' g = 0.37, 95% CI = 0.29-0.64, Z = 5.33, p < 0.01). CONCLUSION: These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine.
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Introduction: Early diagnosis of SAPHO syndrome is easily confused with other common spine-related diseases and infections. There is currently no consensus regarding the diagnosis of SAPHO syndrome, and specific treatments are empirical because of its rarity. Case Presentation: A 62-year-old woman was referred to our department with complaints of low back and lower extremity pain for 2 years, 1.5 years after lumbar spine surgery, and recurrent low back pain for 1 year. Laboratory test results revealed elevated hs-CRP levels and erythrocyte sedimentation rate. Combined with her surgical history and lumbar CT results, adjacent segment degeneration (ASD) was first considered. NSAIDs, analgesics, and supplemental therapies were also administered. However, the patient's symptoms were not significantly relieved. During re-examination, hyperkeratosis with active pustulosis was observed on the patient's palms. Osteitis of the left sacroiliac joint was revealed on imaging. Skeletal ECT revealed a typical "horn sign". The patient was diagnosed with SAPHO syndrome. Based on the original treatment, sulfasalazine enteric-coated tablets, adalimumab (a biological agent of TNF-α), pregabalin, and tramadol sustained-release tablets were administered. The patient reported that her pain was significantly relieved. He was discharged from the hospital and received adalimumab treatment (40 mg once per fortnight in the first 6 months and 40 mg once per month after month 6) in the outpatient clinic. The hyperkeratosis with active pustulosis on both palms fully recovered after 12 months of treatment. The patient was followed up 6 months after full recovery, and no recurrence was found in the symptoms of low back and lower extremity pain and palmar hyperkeratosis with active pustulosis. Conclusion: SAPHO syndrome should be suspected in patients present with osteoarticular and/or dermatological manifestations. Biological agents can be used to treat patients with refractory SAPHO syndrome.
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Milk contains bioactive compounds that have multiple essential benefits. Milk-derived small extracellular vesicles (M-sEVs) have emerged as novel bioactive milk components with various beneficial biological functions and broad applications. The M-sEVs from different mammalian sources have similar composition and bioactive functions. The digestive stability and biocompatibility of the M-sEVs provide a good foundation for their physiological functions. Evidence suggests that M-sEVs promote intestinal, immune, bone, neural, liver, and heart health and show therapeutic effects against cancer, indicating their potential for use in functional foods. In addition, M-sEVs can be developed as natural delivery carriers owing to their superior structural characteristics. Further studies are needed to elucidate the relationship between the specific components and functions of M-sEVs, standardize their extraction processes, and refine relevant clinical trials to advance the future applications of M-sEVs. This review summarizes the structure and composition of M-sEVs isolated from different milk sources and discusses several common extraction methods. Since the introduction of M-sEVs for digestion and absorption, studies have been conducted on their biological functions. Furthermore, we outline the theoretical industrial production route, potential application scenarios of M-sEVs, and the future perspectives of M-sEV research.
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BACKGROUND: The genes of the RECQ DNA helicase family play a part in preserving the stability of the genome and controlling different disease mechanisms. However, the expression features of RECQs in relation to pan-cancer, their correlation with the immune microenvironment of tumors, and the landscape of prognostic power are still undisclosed. METHODS: Various sequence and clinical data extracted from 33 cancers were utilized to generate a comprehensive overview of RECQs in the landscape. Afterward, we discovered variations in gene expression, potential enrichment of functions, genetic alterations, and analysis related to the immune response in tumors. Additionally, we explored the clinical characteristics and diagnostic significance of RECQs. And the important association of RECQL4 with liver hepatocellular carcinoma (LIHC) was investigated. RESULTS: RECQs exhibited extensive mutations in different types of cancers. The expression of RECQ may be influenced by an oncogenic mutation in certain types of cancer, resulting in the observed genomic and epigenetic changes in diverse tumor formations. Furthermore, RECQs originating from tumors exhibited a significant association with the immune microenvironment of the tumor, indicating their potential as promising targets for therapy. Patient prognosis was significantly associated with the majority of genes in the RECQ family. In LIHC, RECQL4 eventually emerged as a separate prognostic determinant. CONCLUSIONS: To summarize, RECQs are essential for the regulation of the immune system in tumors, and RECQL4 serves as a prognostic indicator in LIHC. The results of our study offer fresh perspectives on RECQs from a bioinformatics perspective and emphasize the importance of RECQs in the diagnosis and treatment of cancer.
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The interaction between microglia and astrocytes exhibits a relatively balanced state in order to maintain homeostasis in the healthy central nervous system (CNS). Disease stimuli alter microglia-astrocyte interaction patterns and elicit cell-type-specific responses, resulting in their contribution to various pathological processes. Here, we review the similarities and differences in the activation modes between microglia and astrocytes in various scenarios, encompassing different stages of neural development and a wide range of neural disorders. The aim is to provide a comprehensive understanding of their roles in neural development and regeneration and guiding new strategies for restoring CNS homeostasis.