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The aim of the study was to develop a new whole spinal MRI-based tumor burden scoring method in participants with newly diagnosed multiple myeloma (MM) and to explore its prognostic significance. We prospectively recruited participants with newly diagnosed MM; performed whole spinal MRI (sagittal FSE T1WI, sagittal IDEAL T2WI, and axial FLAIR T2WI) on them; and collected their clinical data, early treatment response, progression-free survival (PFS), and overall survival (OS). We developed a new tumor burden scoring method according to the extent of bone marrow infiltration in five MRI patterns. All participants were divided into good response and poor response groups after four treatment cycles. Univariate, multivariate analyses, and ROC were used to determine the performance of independent predictors. Thresholds for PFS and OS were calculated using X-tile, and their prognostic significance were assessed by Kaplan-Meier. The Kruskal-Wallis H test was used to compare the differences of tumor burden score between the revised International Staging System (R-ISS) stages. The new tumor burden scoring method was used in 62 participants (median score, 12; range, 0-18). The tumor burden score (OR 1.266, p = 0.002) was an independent predictor of poor response and the AUC was 0.838. Higher tumor burden scores were associated with shorter PFS (p = 0.002) and OS (p = 0.011). The tumor burden score was higher in R-ISS-III than in R-ISS-I and R-ISS-II (p = 0.016 and p = 0.006, respectively). The tumor burden score was an excellent predictor of prognosis and may serve as a supplemental marker for R-ISS.
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Mieloma Múltiplo , Neoplasias da Coluna Vertebral , Humanos , Prognóstico , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/terapia , Projetos Piloto , Projetos de Pesquisa , Carga Tumoral , Estadiamento de Neoplasias , Imageamento por Ressonância Magnética , Estudos RetrospectivosRESUMO
The indiscriminate discharge of micropollutants (e.g., dyes, antibiotics, industrial additives, etc.) represents a significant risk to human health, and the removal of these substances from water bodies has become a prominent area of research within the field of environmental remediation. A simple hydrothermal-precipitation-photoreduction method was employed to synthesize novel Z-scheme heterojunction photocatalysts of AgBr/CoWO4/Ag. The catalysts demonstrated remarkable degradation capabilities with regard to a range of micropollutants present in wastewater. Of the catalysts tested, 5AgBr/CoWO4/Ag exhibited the highest degradation rates, reaching 98.58% for Rhodamine B, 86.82% for tetracycline hydrochloride, and 95.60% for 2-mercaptobenzothiazole within 60 min. In particular, the reaction kinetic rate of 5AgBr/CoWO4/Ag towards Rhodamine B degradation (k2 = 0.26278 L mg-1·min-1) is 9 times that of AgBr (k2 = 0.02953 L mg-1·min-1) and 113 times that of CoWO4 (k2 = 0.00233 L mg-1·min-1), which serves to highlight the exceptional photocatalytic activity of the material. The experimental data and subsequent analysis indicated that the enhanced photocatalytic performance can be attributed to two factors: firstly, the electron mediation by Ag nanoparticles leading to improved charge separation efficiency, and secondly, the formation of Z-scheme heterojunctions between AgBr and CoWO4. The cyclic tests provided confirmation of the excellent stability and recyclability of the AgBr/CoWO4/Ag photocatalysts. It is anticipated that this study will facilitate the development of novel methods for the degradation of refractory micropollutants and provide insights into environmental remediation, thereby contributing to the sustainable development of society.
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Neural tube defects (NTDs) represent a developmental disorder of the nervous system that can lead to significant disability in children and impose substantial social burdens. Valproic acid (VPA), a widely prescribed first-line antiepileptic drug for epilepsy and various neurological conditions, has been associated with a 4-fold increase in the risk of NTDs when used during pregnancy. Consequently, urgent efforts are required to identify innovative prevention and treatment approaches for VPA-induced NTDs. Studies have demonstrated that the disruption in the delicate balance between cell proliferation and apoptosis is a crucial factor contributing to NTDs induced by VPA. Encouragingly, our current data reveal that melatonin (MT) significantly inhibits apoptosis while promoting the restoration of neuroepithelial cell proliferation impaired by VPA. Moreover, further investigations demonstrate that MT substantially reduces the incidence of neural tube malformations resulted from VPA exposure, primarily by suppressing apoptosis through the modulation of intracellular reactive oxygen species levels. In addition, the Src/PI3K/ERK signaling pathway appears to play a pivotal role in VPA-induced NTDs, with significant inhibition observed in the affected samples. Notably, MT treatment successfully reinstates Src/PI3K/ERK signaling, thereby offering a potential underlying mechanism for the protective effects of MT against VPA-induced NTDs. In summary, our current study substantiates the considerable protective potential of MT in mitigating VPA-triggered NTDs, thereby offering valuable strategies for the clinical management of VPA-related birth defects.
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Melatonina , Defeitos do Tubo Neural , Gravidez , Feminino , Criança , Humanos , Ácido Valproico , Melatonina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Defeitos do Tubo Neural/induzido quimicamente , Defeitos do Tubo Neural/prevenção & controle , Estresse Oxidativo , Transdução de SinaisRESUMO
Poor tendon-bone interface (TBI) integration is one of the major causes contributing to unsatisfactory healing quality in patients after anterior cruciate ligament (ACL) reconstruction. Type H vessels have been recently found to closely modulate bone formation via regulation of the osteo-angiogenic crosstalk, so the strategies favoring type H vessel formation may be promising therapeutic approaches for improved graft osteointegration. In this study, we reported for the first time the treatment outcome of slit guidance ligand 3 (slit3), a novel proangiogenic factor favoring type H vessel formation, in TBI healing in mice with ACL reconstruction. The mice (n = 87) were divided into three groups for various treatments: hydrogel microparticles (HMP, control group), slit3@HMP, and slit3 neutralizing antibody@HMP (slit3-AB@HMP). Histological analysis, gait performance, radiographic measurement, and biomechanical testing were performed to assess the TBI healing quality. Increased bony ingrowth and reduced fibrous scar tissue was formed at the TBI in the slit3@HMP group when compared to the HMP group. Meanwhile, the slit3-AB@HMP inhibited the osseous ingrowth and increased fibrous scar tissue formation relative to the HMP group. Compared to the HMP group, the slit3@HMP favored type H vessel formation at the TBI while the slit3-AB@HMP impeded it. According to micro-CT assessment, compared to the HMP group, the slit3@HMP significantly increased the peri-tunnel bone mass while the slit3-AB@HMP significantly reduced the peri-tunnel bone mass. The mice in the slit3@HMP group showed the best gait performance in terms of stance time, stride length, paw print area, and stance pressure. Dynamic laxity measurement and tensile testing showed the slit3@HMP group exhibited significantly reduced laxity displacement and improved failure load and stiffness relative to the other two groups. Collectively, the injection of slit3 could be used to enhance tendon-bone integration, which may be ascribed to modulation of angiogenesis-osteogenesis crosstalk coupled by type H vessels.
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Cicatriz , Hidrogéis , Animais , Camundongos , Ligantes , Osso e Ossos/diagnóstico por imagem , TendõesRESUMO
Zymomonas mobilis is a gram-negative facultative anaerobic spore, which is generally recognized as a safe. As a promising ethanologenic organism for large-scale bio-ethanol production, Z. mobilis has also shown a good application prospect in food processing and food additive synthesis for its unique physiological characteristics and excellent industrial characteristics. It not only has obvious advantages in food processing and becomes the biorefinery chassis cell for food additives, but also has a certain healthcare effect on human health. Until to now, most of the research is still in theory and laboratory scale, and further research is also needed to achieve industrial production. This review summarized the physiological characteristics and advantages of Z. mobilis in food industry for the first time and further expounds its research status in food industry from three aspects of food additive synthesis, fermentation applications, and prebiotic efficacy, it will provide a theoretical basis for its development and applications in food industry. This review also discussed the shortcomings of its practical applications in the current food industry, and explored other ways to broaden the applications of Z. mobilis in the food industry, to promote its applications in food processing.
Potential applications of Zymomonas mobilis in food industry summarized for the first time.Research status of Z. mobilis in food additive synthesis, fermentation applications, and probiotics are discussed in details.Future research perspectives of Z. mobilis in food industry further proposed.
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BACKGROUND Previous studies have demonstrated that embryo development and the occurrence of tumors are closely related, as key genes, pathways, miRNAs, and other biological mechanisms are involved in both processes. Extensive research has found that abnormal development of nerve ectodermal cells not only leads to neural tube defects (NTDs), but also neuroectodermal tumors. MATERIAL AND METHODS Genes associated with both NTDs and neuroectodermal tumors were obtained from the DisGeNET database. The STRING database was used to construct the protein-protein interaction (PPI) network and the hub genes were visualized using Cytoscape. Additionally, we predicted the miRNAs targeting the identified genes. Sequencing data obtained from an NTDs mouse model and human samples were used to confirm the bioinformatics results. Moreover, a dual-luciferase report assay was used to validate the targeting relationship between the miRNA-gene pairs identified. RESULTS A total of 104 intersection genes of NTDs-related and neuroectodermal tumors-related genes were obtained; 20 of these genes were differentially expressed in NTDs samples and had very close interactions. Among 10 hub genes, we identified 3 important susceptibility genes differentially expressed both in RA-induced NTDs mice and human glioblastoma samples: Ncam1, Shh, and Ascl1. Among these, we found that the Ncam1 expression level was regulated by mmu-miR-30a-5p, and the Ascl1 expression level was regulated by mmu-miR-375-3p. CONCLUSIONS In conclusion, we identified differentially expressed genes and a potential miRNA-mediated regulation mechanism shared between NTDs and neuroectodermal tumors that may guide future studies aiming to find novel therapeutic targets for NTDs or neuroectodermal tumors.
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MicroRNAs , Defeitos do Tubo Neural , Tumores Neuroectodérmicos , Animais , Biologia Computacional/métodos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Defeitos do Tubo Neural/genética , Mapas de Interação de Proteínas/genéticaRESUMO
In order to further explore the therapeutic effects of high-frequency and low-frequency repetitive transcranial magnetic stimulation on depression and cognitive function in the elderly, this paper proposed a study on cortical plasticity mechanism and efficacy prediction of repetitive transcranial magnetic stimulation based on continuous short pulse fast pulse stimulation (CTBS). This paper selected 92 patients with depression in a hospital from January to December 2020 as the research object and divided them into control group, low-frequency group, and high-frequency group, 31 cases, 29 cases, and 32 cases, respectively. The continuous short pulse rapid pulse stimulation (CTBS) mode was used to explore the effect of brain network on patients' emotional processing. After clinical treatment contrast, there was no significant difference in HAMD-24 scores and RBANS scores before treatment (P > 0.05), and there was a significant negative correlation between factors of cognitive impairment in patients and RBANS scores (P < 0.01 or P < 0.05), so it was proved that the repeated transcranial magnetic stimulation (cTBS) could be used as an effective treatment for depression.
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Córtex Motor , Estimulação Magnética Transcraniana , Idoso , Depressão/terapia , Potencial Evocado Motor/fisiologia , Humanos , Córtex Motor/fisiologia , Resultado do TratamentoRESUMO
Background Acute myeloid leukemia (AML) features relatively low overall survival (OS). Intravoxel incoherent motion (IVIM) diffusion-weighted MRI separates tissue microcapillary perfusion and diffusivity and may have potential for helping to assess prognosis in infiltrated marrow disease apart from solid tumor. Thus, a study of overall survival would contribute to clarifying the value of IVIM for assessing long-term prognosis in AML. Purpose To determine whether the IVIM-derived parameters of infiltrated bone marrow may be associated with OS in newly diagnosed AML. Materials and Methods This prospective study enrolled participants with newly diagnosed AML between July 2014 to March 2016 consecutively. Participants underwent MRI of the lumbar spine by using an IVIM sequence. Participant clinical characteristics and OS were collected. The median of follow-up period was 20 months (range, 1-56 months). The IVIM parameters (pseudoperfusion fraction, f; diffusion coefficient, D; and pseudodiffusion coefficient, D*) were obtained. A nonparametric log-rank test was used to identify the threshold of IVIM parameters for OS. Univariable Kaplan-Meier and multivariable Cox proportional hazards regression analyses were performed to investigate prognostic significance of possible indicators. Results Fifty-three participants (mean age, 42 years ± 17; 30 men) were evaluated. Nonparametric log-rank test results showed that the thresholds of f and D values for OS were 31.0% and 0.2 × 10-3 mm2/sec, respectively. Univariable analyses indicated that high f value (>31.0%) and low D value (≤0.2 × 10-3 mm2/sec) were associated with shorter OS (P = .003 and .01, respectively). An f value greater than 31.0% (hazard ratio, 2.4; 95% confidence interval: 1.0, 5.6; P = .046) was associated with OS, independent of clinical confounders (age, karyotype, and white blood cell counts) in a multivariable analysis. Conclusion Pseudoperfusion fraction and diffusion coefficient from intravoxel incoherent motion diffusion-weighted MRI may be viable prognosis predictors of newly diagnosed acute myeloid leukemia. © RSNA, 2020.
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Medula Óssea/diagnóstico por imagem , Medula Óssea/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/patologia , Infiltração Leucêmica , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: An accurate and noninvasive method is of great importance to assess angiogenesis and cellularity of bone marrow in acute leukemia (AL). PURPOSE: To investigate whether the intravoxel incoherent motion (IVIM) parameters correlate with the histological characteristics of infiltrated marrow in AL patients and compare the difference between acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). STUDY TYPE: Prospective. POPULATION MODEL: Forty newly diagnosed patients with AL, including 20 AML and 20 ALL. FIELD STRENGTH/SEQUENCE: 1.5T/T1 WI and IVIM. ASSESSMENT: IVIM-derived parameters (true diffusion coefficient D, pseudodiffusion coefficient D*, and perfusion fraction, f) were measured in lumbar marrow. Histopathological analyses were performed from samples of marrow biopsy. STATISTICAL TESTS: The correlations between IVIM parameters and histological parameters used the Spearman correlation test. The difference of IVIM parameters and histological parameters between ALL and AML groups used the unpaired t-test or Mann-Whitney U-test, as appropriate. RESULTS: The f was positively correlated with microvessel density (MVD) in patients with ALL, AML, and AL (r = 0.740, P = 0.006; r = 0.771, P < 0.001; and r = 0.750, P < 0.001, respectively). There were no significant correlations between D and bone marrow cellularity in the three groups (r = -0.289, P = 0.362; r = 0.281, P = 0.292; and r = 0.058, P = 0.769, respectively). D and f values of ALL were higher than that of AML group (t = 3.332, P = 0.003 and t = 2.600, P = 0.014, respectively). MVD was higher in ALL than AML (t = 2.120, P = 0.044), whereas bone marrow cellularity had no significant difference between AML and ALL (t = -0.682, P = 0.501). DATA CONCLUSION: The f value derived from IVIM in bone marrow was positively correlated with MVD, while f might be able to show a difference of vascularity between ALL and AML. Therefore, the f value can be used as an alternative imaging marker of angiogenesis in marrow of AL patients. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1720-1726.
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Medula Óssea , Leucemia Mieloide Aguda , Medula Óssea/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Humanos , Leucemia Mieloide Aguda/diagnóstico por imagem , Movimento (Física) , Estudos ProspectivosRESUMO
Statins have been suggested in previous studies to play a protective role in experimental cerebral aneurysm (CA) models; however, no evidence supports that the application of statins can protect against aneurysm rupture in humans, and the risks of lipid levels and aneurysms remain unknown. Therefore, this meta-analysis aimed to summarize and update the epidemiological evidence to systematically assess the relationships of statin therapy and hyperlipidemia with the incidence, rupture, postrepair mortality, and all-cause mortality of abdominal aortic aneurysm (AAA) and CA. Related studies were initially retrieved from the electronic databases PubMed, Embase, and Cochrane Library from inception to August 4, 2018. Subsequently, 33 studies were enrolled into this meta-analysis, and the maximum adjusted risk ratios (RRs) as well as the corresponding 95% confidence intervals were extracted. Finally, a total of 32 observational studies involving 150,134 participants were enrolled into this meta-analysis. The RRs of statin therapy for AAA incidence, AAA rupture, CA rupture, postrepair mortality, all-cause mortality, and adverse events were 1.83 (0.56-5.98), 0.67 (0.47-0.97), 0.50 (0.18-1.36), 0.60 (0.48-0.74), 0.66 (0.58-0.75), and 0.58 (0.47-0.71), respectively. Besides, the RR of hyperlipidemia for CA rupture was 0.79 (0.67-0.93). Our findings suggested that statin therapy could reduce the risks of AAA rupture, postrepair mortality, all-cause mortality, and adverse events, without inducing the risk of AAA incidence or CA rupture, and that hyperlipidemia was associated with a lower risk of CA rupture.
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Aneurisma da Aorta Abdominal/mortalidade , Ruptura Aórtica/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Aneurisma Intracraniano/mortalidade , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Abdominal/cirurgia , Ruptura Aórtica/cirurgia , Progressão da Doença , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hiperlipidemias/mortalidade , Incidência , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Fatores de Proteção , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
The biogenesis of ribosomes in vivo is an essential process for cellular functions. Transcription of ribosomal RNA (rRNA) genes is the rate-limiting step in ribosome biogenesis controlled by environmental conditions. Here, we investigated the role of folate antagonist on changes of DNA double-strand breaks (DSBs) landscape in mouse embryonic stem cells. A significant DSB enhancement was detected in the genome of these cells and a large majority of these DSBs were found in rRNA genes. Furthermore, spontaneous DSBs in cells under folate deficiency conditions were located exclusively within the rRNA gene units, representing a H3K4me1 hallmark. Enrichment H3K4me1 at the hot spots of DSB regions enhanced the recruitment of upstream binding factor (UBF) to rRNA genes, resulting in the increment of rRNA genes transcription. Supplement of folate resulted in a restored UBF binding across DNA breakage sites of rRNA genes, and normal rRNA gene transcription. In samples from neural tube defects (NTDs) with low folate level, up-regulation of rRNA gene transcription was observed, along with aberrant UBF level. Our results present a new view by which alterations in folate levels affects DNA breakage through epigenetic control leading to the regulation of rRNA gene transcription during the early stage of development.
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Quebras de DNA de Cadeia Dupla , Deficiência de Ácido Fólico/genética , Regulação da Expressão Gênica no Desenvolvimento , Genes de RNAr , Proteínas Pol1 do Complexo de Iniciação de Transcrição/metabolismo , Transcrição Gênica , Animais , Células Cultivadas , Células-Tronco Embrionárias/metabolismo , Feto/metabolismo , Antagonistas do Ácido Fólico/toxicidade , Deficiência de Ácido Fólico/metabolismo , Fase G1/genética , Histonas/metabolismo , Leucovorina/farmacologia , Metotrexato/toxicidade , Camundongos , Defeitos do Tubo Neural/genética , Defeitos do Tubo Neural/metabolismoRESUMO
BACKGROUND: Type 2 diabetes mellitus, obesity and hepatic steatosis showed a strong correlation with metabolic syndrome. However, data on the influence of pancreatic steatosis on metabolic syndrome are lacking. OBJECTIVE: Our aim is to perform the prevalence of pancreatic steatosis in adults and its association with metabolic syndrome in a Chinese population. METHODS: This was a cross-sectional study, randomly selected. A total of 1190 health examination subjects were recruited. Pancreatic steatosis or hepatic steatosis was diagnosed via trans-abdominal sonography. The clinical and metabolic parameters were compared between the two groups, and their associations with pancreatic steatosis were examined. RESULTS: The prevalence of pancreatic steatosis was 30.7%. The presence of pancreatic steatosis was significantly increased by age, gender, central obesity, hepatic steatosis, hypertriglyceridemia and hyperglycemia. In the logistic regression analysis, age (P < 0.05), central obesity (P < 0.01), diabetes (P < 0.05), hypertriglyceridemia (P < 0.05) and hepatic steatosis (P < 0.01) were independently associated with pancreatic steatosis. The number of the parameters of the metabolic syndrome in pancreatic steatosis group was more than that in non-pancreatic steatosis group [(2.5 ± 1.1) vs (1.4 ± 1.2)] (P < 0.01). CONCLUSION: The pancreatic steatosis is strongly associated with the parameters of metabolic syndrome, such as central obesity, diabetes, and hepatic steatosis.
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Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Pancreatopatias/complicações , Pancreatopatias/epidemiologia , Adulto , Fatores Etários , Idoso , Povo Asiático/estatística & dados numéricos , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Fígado Gorduroso/complicações , Feminino , Humanos , Hiperglicemia/complicações , Hiperglicemia/epidemiologia , Hipertrigliceridemia/complicações , Hipertrigliceridemia/epidemiologia , Resistência à Insulina , Masculino , Síndrome Metabólica/diagnóstico por imagem , Pessoa de Meia-Idade , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Pâncreas/diagnóstico por imagem , Pancreatopatias/diagnóstico por imagem , Prevalência , Fatores de Risco , Fatores Sexuais , UltrassonografiaRESUMO
OBJECTIVE: Natural killer (NK) cells serve as primary immune surveillance and are partially regulated by combinations of killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen-C (HLA-C) ligands. Alterations in NK cell activity have been associated with Hashimoto thyroiditis (HT). The aim of this study was to determine whether certain KIR/HLA-C genotype combinations play a role in HT pathogenesis. METHODS: The present study enrolled 107 unrelated HT patients and 108 random healthy individuals in a case-control study. Blood was collected for DNA extraction; typing of KIR genes and HLA-C alleles was performed by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by electrophoresis on agarose gels. RESULTS: Among a panel of KIR2D/HLA-C genotype combinations, the frequency of KIR2DS2/HLA-C1 was significantly increased in HT patients compared to controls (33.64% vs. 12.96%, P<.001). To further analyze the precise genotype, we investigated inhibitory or activating KIR/HLA-C gene pairs when their corresponding activating or inhibitory KIR genes were absent in the 2 groups. Only the frequency of KIR2DS2(-)2DL2/3(+)HLA-C1(+) was significantly decreased in HT patients compared to controls (48.60% vs. 70.37%, P = .001). CONCLUSION: Our data suggest that KIR2DS2/HLA-C1 may correlate with HT pathogenesis. On the contrary, the predominance of KIR2DL2/3/HLA-C1 in the absence of KIR2DS2 suggests a potential inhibitory role in HT pathogenesis. In conclusion, our findings may further elucidate the mechanisms underlying the pathogenesis of HT and other autoimmune diseases. ABBREVIATIONS: HLA-C = human leukocyte antigen-C HT = Hashimoto thyroiditis KIR = killer immunoglobulin-like receptor NK = natural killer PCR = polymerase chain reaction.
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Antígenos HLA-C/genética , Doença de Hashimoto/genética , Receptores KIR/genética , Adulto , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Predisposição Genética para Doença , Doença de Hashimoto/imunologia , Humanos , Ligantes , Masculino , Pessoa de Meia-IdadeRESUMO
Diabetic retinopathy is a prevalent and severe microvascular complication of diabetes, often causing visual impairment and blindness in adults. This condition significantly impacts the quality of life for many diabetes patients worldwide. Berberine (BBR), a bioactive compound known for its effects on blood glucose levels, has shown promise in managing diabetic complications. However, the exact mechanism of how BBR influences the development of diabetic retinopathy remains unclear. In this study, we focused on synthesizing a formulation derived from BBR and assessing its protective effects against diabetic retinopathy. The formulation was created using a green synthesis method and thoroughly characterized. In vitro studies demonstrated the antioxidant activity of the formulation against 2,2-diphenyl-1-picryl-hydrazyl-hydrate. We also examined the NF-κB signaling pathway at a molecular level using real-time polymerase chain reaction. To mimic diabetic retinopathy in a controlled setting, a diabetic rat model was established through streptozotocin injection. The rats were divided into normal, diabetic, and treatment groups. The treatment group received the formulated treatment via intragastric administration for several weeks, while the other groups received normal saline. Evaluation of histopathological characteristics and microstructural changes in the retina using hematoxylin and eosin staining revealed that the bioactive compound-derived nanoparticle exhibited favorable biological, chemical, and physical properties. Treatment with the formulation effectively reduced oxidative stress induced by diabetes and inhibited the NF-κB signaling pathway in the diabetic rat model. Under high glucose conditions, oxidative stress was heightened, leading to mitochondria-dependent cell apoptosis in Müller cells via the activation of the NF-κB signaling pathway. The bioactive compound-derived formulation counteracted these effects by decreasing IκB phosphorylation, preventing NF-κB nuclear translocation, and deactivating the NF-κB signaling pathway. Furthermore, treatment with the bioactive compound-derived formulation mitigated retinal micro- and ultrastructural changes associated with diabetic retinopathy. These results indicate that the formulation protects against diabetic retinopathy by suppressing oxidative stress, reducing cell apoptosis, and deactivating the NF-κB signaling pathway. This suggests that the bioactive compound-derived formulation could be a promising therapeutic option for diabetic retinopathy.
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The low-cost carbon source, acetate, was utilized to feed a linoleic acid-rich Chlorella sorokiniana for microalgal biomass and lipid accumulation. Remarkably high tolerance capability to high acetate dosage up to 30 g/L was observed, with heterotrophy being the preferred trophic mode for algal growth and lipogenesis when supplemented 20 g/L acetate. Transcriptome analysis revealed a marked activation of pathways involved in acetate bioconversion and lipogenesis upon exposure to high-level of acetate. However, the enhancement of photorespiration inhibited photosynthesis, which ultimately led to a decrease in biomass and lipid under mixotrophy. Heterotrophic acetate-feeding generated more superior amino acid profiling of algal biomass and a predominant linoleic acid content (50 %). Heterotrophic repeat fed-batch strategy in 5 L fermenter significantly increased the growth performance and lipid titer, with the highest levels achieved being 23.4 g/L and 7.0 g/L, respectively. This work provides a viable approach for bio-products production through acetate-based heterotrophic algal cultivation.
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Chlorella , Microalgas , Chlorella/metabolismo , Ácido Linoleico/metabolismo , Microalgas/metabolismo , Processos Heterotróficos , Biomassa , AcetatosRESUMO
Apple peel is a typical lignocellulosic food by-product rich in functional components. In this work, apple peel was solid-state fermented with Aspergillus oryzae with an aim to modulate its composition and bioactivity. The results showed that A. oryzae fermentation substantially tailored the composition, improved the antioxidant activity and prebiotic potential of apple peel. Upon the fermentation, 1) free phenolics increased and antioxidant activity improved; 2) the pectin substances degraded significantly, along with a decrease in soluble dietary fiber while an increase in insoluble dietary fiber; 3) the in vitro fermentability increased as indicated by the increase in total acid production. The gut microbiota was shaped with more health-promoting potentials, such as higher abundances of Lactobacillus, Bifidobacterium, Megamonas and Prevotella-9 as well as lower abundances of Enterobacter and Echerichia-Shigella. This work is conducive to the modification of apple peel as a potential ingredient in food formulations.
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Purpose: To investigate the value of quantitative longitudinal relaxation time (T1), transverse relaxation time (T2), and proton density (PD) maps derived from synthetic magnetic resonance imaging (MRI) for evaluating the status of lymphovascular space invasion (LVSI) in cervical squamous cell carcinoma (CSCC) without lymph node metastasis (LNM). Material and methods: Patients with suspected cervical cancer who visited our hospital from May 2020 to March 2023 were collected. All patients underwent preoperative MRI, including routine sequences and synthetic MRI. Patients with pathologically confirmed CSCC without lymphatic metastasis were included in this study. The subjects were divided into negative- and positive-LVSI groups based on the status of LVSI. Quantitative parameters of T1, T2, and PD values derived from synthetic MRI were compared between the two groups using independent samples t-test. Receiver operating characteristic curves were used to determine the diagnostic efficacy of the parameters. Results: 59 patients were enrolled in this study and were classified as positive (n = 32) and negative LVSI groups (n = 27). T1 and T2 values showed significant differences in differentiating negative-LVSI from positive-LVSI CSCC (1307.39 ± 122.02 vs. 1193.03 ± 107.86, P<0.0001; 88.42 ± 7.24 vs. 80.99 ± 5.50, P<0.0001, respectively). The area under the curve (AUC) for T1, T2 values and a combination of T1 and T2 values were 0.756, 0.799, 0.834 respectively, and there is no statistically significant difference in the diagnostic efficacy between individual and combined diagnosis of each parameter. Conclusions: Quantitative parameters derived from synthetic MRI can be used to evaluate the LVSI status in patients with CSCC without LNM.
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An integrated process for the co-production of cellulosic ethanol and microalgal biomass by fixing CO2 generated from bioethanol fermentation is proposed. Specifically, over one-fifth of the fermentative carbon was converted into high-purity CO2 during ethanol production. The optimal concentration of 4 % CO2 was identified for the growth and metabolism of Chlorella sp. BWY-1. A multiple short-term intermittent CO2 supply system was established to efficiently fix and recycle the waste CO2. Using this system, economical co-production of cellulosic ethanol by Zymomonas mobilis and microalgal biomass in biogas slurry wastewater was achieved, resulting in the production of ethanol at a rate of 0.4 g/L/h and a fixed fermentation CO2 of 3.1 g/L/d. Moreover, the amounts of algal biomass and chlorophyll a increased by over 50 % and two-fold, respectively. Through techno-economic analysis, the integrated process demonstrated its cost-effectiveness for cellulosic ethanol production. This study presents an innovative approach to a low-carbon circular bioeconomy.
Assuntos
Chlorella , Microalgas , Fermentação , Dióxido de Carbono/metabolismo , Biomassa , Etanol/metabolismo , Microalgas/metabolismo , Chlorella/metabolismo , Clorofila A , BiocombustíveisRESUMO
Background: The spleen is a frequent organ of leukemia metastasis. This study aimed to investigate the value of intravoxel incoherent motion (IVIM) diffusion-weighted magnetic resonance imaging (MRI) for assessing pathologic changes in the spleen and identifying early spleen involvement in patients with acute leukemia (AL). Methods: Patients with newly diagnosed AL and healthy controls were recruited between June 2020 and November 2022. All participants underwent abdominal IVIM diffusion-weighted imaging (DWI) at our hospital. IVIM parameters [pure diffusion coefficient (D); pseudo-diffusion coefficient (D*); and pseudo-perfusion fraction (f)] of the spleen were calculated by the segmented fitting method, and perfusion-diffusion ratio (PDR) was further calculated from the values of D, D* and f. Spleen volumes (SVs) were obtained by manually segmenting the spleen layer by layer. Clinical biomarkers of AL patients were collected. Patients were divided into splenomegaly group and normal SV group according to the individualized reference intervals for SV. IVIM parameters were compared among the control group, AL with normal SV group, and AL with splenomegaly group using one-way analysis of variance, followed by pairwise post hoc comparisons. The correlations of IVIM parameters with clinical biomarkers were analyzed in AL patients. The diagnostic performances of IVIM parameters and their combinations for differentiating among the three groups were compared. Results: Seventy-nine AL patients (AL with splenomegaly: n=54; AL with normal SV: n=25) and 55 healthy controls were evaluated. IVIM parameters were significantly different among the three groups (P<0.001 for D, D* and f; P=0.001 for PDR). D and PDR showed significant differences between the control and AL with normal SV groups in pairwise comparisons (P<0.001, and P=0.031, respectively). D was correlated with white blood cell (WBC) counts (r=-0.424; 95% CI: -0.570, -0.211; P<0.001), lactate dehydrogenase (LDH) (r=-0.285; 95% CI: -0.486, -0.011; P=0.011), and bone marrow blasts (r=-0.283; 95% CI: -0.476, -0.067; P=0.012). D* (r=-0.276; 95% CI: -0.470, -0.025; P=0.014), f (r=0.514; 95% CI: 0.342, 0.664; P<0.001) and PDR (r=0.343; 95% CI: 0.208, 0.549; P=0.002) were correlated with LDH. The combination of IVIM parameters (AUC: 0.830; 95% CI: 0.729, 0.905) demonstrated better diagnostic efficacy than the single D* (AUC: 0.721; 95% CI: 0.608, 0.816; Delong test: Z=2.012, P=0.044) and f (AUC: 0.647; 95% CI: 0.532, 0.752; Delong test: Z=2.829, P=0.005), but was not significantly different from the single D (AUC: 0.756; 95% CI: 0.647, 0.846; Delong test: Z=1.676, P=0.094) in differentiating the splenomegaly group and normal SV group. Conclusions: IVIM diffusion-weighted MRI could be a potential alternative for assessing pathologic changes in the spleen from cellularity and angiogenesis, and D and PDR may be viable indicators to identify early spleen involvement in patients with AL.
RESUMO
BACKGROUND: The value of SyMRI-derived parameters from lumbar marrow for predicting early treatment response and optimizing the risk stratification of the Revised International Staging System (R-ISS) in participants with multiple myeloma (MM) is unknown. METHODS: We prospectively enrolled participants with newly diagnosed MM before treatment. The SyMRI of lumbar marrow was used to calculate T1, T2, and PD values and the clinical features were collected. All participants were divided into good response (≥VGPR) and poor response (Assuntos
Mieloma Múltiplo
, Humanos
, Masculino
, Feminino
, Prognóstico
, Mieloma Múltiplo/diagnóstico por imagem
, Mieloma Múltiplo/patologia
, Medula Óssea/diagnóstico por imagem
, Medula Óssea/patologia
, Projetos Piloto
, Estadiamento de Neoplasias
, Imageamento por Ressonância Magnética
, Estudos Retrospectivos