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1.
Amino Acids ; 2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37689600

RESUMO

Narcolepsy is a chronic and underrecognized sleep disorder characterized by excessive daytime sleepiness and cataplexy. Furthermore, narcolepsy type 1 (NT1) has serious negative impacts on an individual's health, society, and the economy. Currently, many sleep centers lack the means to measure orexin levels in the cerebrospinal fluid. We aimed to analyze the characteristics of metabolite changes in patients with NT1, measured by ultra-performance liquid chromatography-tandem mass spectrometry. A principal component analysis (PCA), an orthogonal partial least square discriminant analysis (OPLS-DA), t tests, and volcano plots were used to construct a model of abnormal metabolic pathways in narcolepsy. We identified molecular changes in serum specimens from narcolepsy patients and compared them with control groups, including dehydroepiandrosterone, epinephrine, N-methyl-D-aspartic acid, and other metabolites, based on an OPLS-loading plot analysis. Nine metabolites yielded an area under the receiver operating curve > 0.75. Meanwhile, seven abnormal metabolic pathways were correlated with differential metabolites, such as metabolic pathways; neuroactive ligand‒receptor interaction; and glycine, serine, and threonine metabolism. To our knowledge, this is the first study to reveal the characteristic metabolite changes in sera from NT1 patients for the selection of potential blood biomarkers and the elucidation of NT1 pathogenesis.

2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 40(10): 1292-1295, 2023 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-37730234

RESUMO

OBJECTIVE: To analyze the genetic characteristics of a child with Meier-Gorlin syndrome (MGS) due to a homozygous variant of the ORC6 gene. METHODS: A child who was admitted to the Children's Hospital Affiliated to Soochow University on March 25, 2019 due to growth retardation was selected as the study subject. Clinical data of the child was collected. Whole exome sequencing was carried out for the child. Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 8-year-and-3-month-old male, has featured short stature, small ears, bilateral cryptorchidism and patellar dysplasia. His parents were of first cousins. The child was found to harbor a homozygous c.712A>T (p.K238*) missense variant of the ORC6 gene, which may lead to premature termination of protein translation. Sanger sequencing confirmed that both of his parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was classified as pathogenic (PVS1_Moderate+PM2_Supporting+PM3+PP3+PP4). CONCLUSION: The homozygous c.712A>T (p.K238*) variant probably underlay the MGS in this child.


Assuntos
Microtia Congênita , Nanismo , Humanos , Lactente , Masculino , Biologia Computacional , Microtia Congênita/genética , Nanismo/genética , Transtornos do Crescimento/genética , Complexo de Reconhecimento de Origem/genética
3.
Sci Total Environ ; 905: 166852, 2023 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-37717750

RESUMO

Peroxyacetyl nitrate (PAN) is a typical secondary photochemical product in the atmospheric environment with significant adverse effects on human health and plant growth. In this study, PAN and other pollutants, as well as meteorological conditions were observed intensively from August to September in 2022 at a typical urban sampling site in Beijing, China. The mean and maximum PAN concentrations during the observation period were 1.00 ± 0.97 ppb and 4.84 ppb, respectively. Severe photochemical pollution occurred during the observation period, with the mean PAN concentration about 3.1 times higher than that during the clean period. There was a good positive correlation between O3 and PAN, and their correlation was higher during the O3 exposure period than that during the clean period. The simulated results by box-model coupled with the Master Chemical Mechanism (MCM v3.3.1) showed that the O3-related reactions were the largest sources of OH radicals during O3 exposure period, which was conducive to the co-contamination of PAN and O3. Acetaldehyde (CH3CHO) and methylglyoxal (MGLY) were the largest OVOCs precursors of peroxyacetyl radicals (PA), with the contributions to the total PA generated by OVOCs about 67 % - 83 % and 17 % - 30 %, respectively. The reduction of emissions from liquefied petroleum gas (LPG) and solvent usage has the highest reduction effect on PAN and O3, followed by the control of gasoline vehicle exhaust emissions. This study deepens the understanding of the PAN photochemistry in urban areas with high O3 background conditions and the impact of anthropogenic activities on the photochemical pollution. Meanwhile, the findings of this study highlight the necessity of strengthening anthropogenic emissions control to effectively reduce the co-contamination of PAN and O3 in Beijing in the future.

4.
Sci Total Environ ; 905: 166987, 2023 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-37717781

RESUMO

The Pearl River Delta (PRD) has long been plagued by severe O3 pollution, particularly during the autumn. A regional O3 pollution episode influenced by the Western Pacific Subtropical High in September 2021 was characterized by near-surface O3 escalation due to strong photochemical reactions within the planetary boundary layer. This event was targeted to develop effective control strategies through investigation of precursor control type and scope based on the high-order decoupled direct method (HDDM) and integrated source apportionment method (ISAM) of CMAQ. Generally, the majority of areas (67.0 %) were under NOx-limited regime, which should strengthen afternoon NOx control inferred by positive convex O3 responses. However, high emission and heavily polluted areas located in central PRD were under VOC-limited regime (11.6 %) or mixed regime (15.0 %). The remaining areas (6.4 %) were under NOx-titration or insensitive conditions. Regarding source apportionment, Guangdong province contributed 32.3 %-58.4 % to MDA8 O3 of PRD, especially higher proportion (>50 %) to central areas. Overall, local-focused NOx/VOC emission reductions had limited effects on O3 mitigation for receptor cities compared to regional-cooperative regulation. When region-wide VOC emission reduction was implemented, MDA8 O3 in VOC-limited grids exhibited the largest declines (2.3 %-4.1 %, 3.9- 7.0 µg·m-3). However, unified NOx control contributed to increasing MDA8 O3 in VOC-limited grids (most stations located for air quality evaluation) whereas decreased MDA8 O3 by 2.1 %- 5.7 %, 3.0- 8.2 µg·m-3 in large-scale NOx-limited grids. The sensitivity-oriented regional control avoided O3 rebound and achieved the greatest decline of 3.4 %- 5.0 %, 5.7- 8.4 µg·m-3 in VOC-limited grids; additionally, time-refined dynamic aggressive NOx control decreased peak O3 by an extra 1.2- 6 µg·m-3, both of which facilitate the regulation for the forecasting O3 episodes. These findings suggest that in heavily polluted environments, the enhancement of O3 regulation benefits requires meticulous, coordinated, and dynamic NOx and VOC controls spanning the entire region based on high-resolution analysis of heterogeneous O3-NOx-VOC sensitivity. Furthermore, emission reduction gains should be more reasonably reflected through increasing in-situ observations covering multi-sensitivity regions.

5.
Sci Total Environ ; : 167240, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37739073

RESUMO

Inland waters are receiving increasing attention due to their importance in the global carbon cycle. However, the dynamics of CO2 emissions and the related mechanisms from ditches remain unclear. In this study, field sampling and an incubation experiment were conducted to explore the effects and mechanisms, especially the coupling effects between carbon fractions, bacteria, and protists of different ditch levels (sublateral ditch, farm ditch, and lateral ditch) and sediment depths (0-20 cm, 20-40 cm) on carbon dynamics in the Lower Yellow River. Results indicated that sublateral ditches nearest to farmland had the highest accumulative carbon mineralization (0-20 cm 1.38 g C kg-1; 20-40 cm 0.89 g C kg-1), equivalent to that of farmland, followed by the lateral ditch (0-20 cm 0.84 g C kg-1; 20-40 cm 0.50 g C kg-1) and the farm ditch (0-20 cm 0.67 g C kg-1; 20-40 cm 0.26 g C kg-1). Carbon emissions from ditches are mainly regulated by SOC (36.97 %), bacteria (29.2 %), and protists (18.95 %). Specifically, the mineralization of flooded lateral ditches is attributed to protist diversity. In contrast, SOC, bacterial and protistan diversity in the farm ditch significantly impacted carbon emissions, with SOC as the dominant factor, while the bacterial composition and SOC contributed more to CO2 emissions in the sublateral ditch. Our results highlight the importance of carbon emissions from ditches, especially those closest to farmland, which may be a crucial ignored source of carbon emissions. This study provides new insights into the construction and management of farmland irrigation and drainage in the aspects of carbon sequestration.

6.
IUBMB Life ; 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37728571

RESUMO

The molecular mechanisms of glioblastoma (GBM) are unclear, and the prognosis is poor. Spinster homolog 2 (SPNS2) is reportedly involved in pathological processes such as immune response, vascular development, and cancer. However, the biological function and molecular role of SPNS2 in GBM are unclear. SPNS2 is aberrantly low expressed in glioma. Survival curves, risk scores, prognostic nomograms, and univariate and multifactorial Cox regression analyses showed that SPNS2 is an independent prognostic indicator significantly associated with glioma progression and prognosis. Cell function assays and in vivo xenograft transplantation were performed that downregulation of SPNS2 promoted GBM cell growth, migration, invasion, epithelial-mesenchymal transition (EMT), anti-apoptosis, drug resistance, and stemness, while overexpression of SPNS2 had the opposite effect. Meanwhile, the functional enrichment and signaling pathways of SPNS2 in the Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), and RNA sequencing were analyzed by Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene set enrichment analysis (GSEA). The above results were related to the inhibition of the PTEN/PI3K/AKT pathway by SPNS2. In addition, we predicted that SPNS2 is closely associated with immune infiltration in the tumor microenvironment by four immune algorithms, ESTIMATE, TIMER, CIBERSORT, and QUANTISEQ. In particular, SPNS2 was negatively correlated with the infiltration of most immune cells, immunomodulators, and chemokines. Finally, single-cell sequencing analysis also revealed that SPNS2 was remarkably correlated with macrophages, and downregulation of SPNS2 promotes the expression of M2-like macrophages. This study provides new evidence that SPNS2 inhibits malignant progression, stemness, and immune infiltration of GBM cells through PTEN/PI3K/AKT pathway. SPNS2 may become a new diagnostic indicator and potential immunotherapeutic target for glioma.

7.
Brain Res ; 1821: 148579, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37739333

RESUMO

OBJECTIVE: Tardive dyskinesia (TD) is a medically induced movement disorder that occurs as a result of long-term use of antipsychotic medications, commonly seen in patients with schizophrenia (SCZ). The study aimed to investigate the relationship between single nucleotide polymorphisms (SNPs) of the CNR1 gene, TD and cognitive impairments in a Chinese population with SCZ. METHODS: A total of 216 SCZ patients were recruited. The participants were divided into TD and without TD (WTD) groups using the Schooler-Kane International Diagnostic Criteria. The severity of TD was assessed using the Abnormal Involuntary Movement Scale (AIMS). Cognitive function was assessed using the Repeatable Battery for Assessment of Neuropsychological Status (RBANS) scale. Hardy-Weinberg equilibrium tests, chained disequilibrium analyses and haplotype analyses were performed using SHE-sis software. To explore the main effects of TD diagnosis, genotype and cognitive function, as well as interaction effects, analysis of covariance (ANCOVA) was employed. RESULTS: The prevalence of TD was approximately 27.3%. Significant differences were observed in the rs806368 CT genotype and rs806370 TC genotype within the hypercongenic pattern between the male TD and WTD groups (OR = 2.508, 95% CI: 1.055-5.961, p = 0.037; OR = 2.552, 95% CI: 1.073-6.069, p = 0.034). Among TD patients, those carrying the rs806368 CC genotype exhibited higher limb trunk scores (p < 0.05). Moreover, there was a statistically significant difference in visuospatial/construction between the TD and WTD groups (p = 0.04), and a borderline significant difference in visuospatial/construction when considering the interaction between TD diagnosis and genotype at the rs806368 locus (p = 0.05). CONCLUSION: CNR1 rs806368 and rs806370 polymorphisms may play a role in TD susceptibility. Additionally, CNR1 gene polymorphisms were associated with the severity of involuntary movements and cognitive impairments in TD patients.

8.
J Ethnopharmacol ; 319(Pt 2): 117167, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37716489

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: SiJunZi decoction (SJZD), one of the traditional Chinese medicine formulas, has been clinically and traditionally used to improve glucose and lipid metabolism and promote bone remodeling. AIM OF THE STUDY: To study the actions and mechanisms of SJZD on bone remodeling in a type 2 diabetes mouse model. MATERIALS AND METHODS: Diabetic mice generated with a high-fat diet (HFD) and streptozotocin (STZ) were subjected to SJZD treatment for 8 weeks. Blood glucose and lipid profile, redox status and bone metabolism were determined by ELISA or biochemical assays. Bone quality was evaluated by micro-CT, three-point bending assay and Fourier transform infrared spectrum (FTIR). Bone histomorphometry alterations were evaluated by Hematoxylin-Eosin (H&E), tartrate resistant acid phosphatase (TRAP) staining and Safranin O-fast green staining. The expressions of superoxide dismutase 1 (SOD1), advanced glycation end products (AGEs), receptor for advanced glycosylation end products (RAGE), phosphorylated nuclear factor kappa-B (p-NF-κB), NF-κB, cathepsin K, semaphorin 3A (Sema3A), insulin-like growth factor 1 (IGF1), p-GSK-3ß, (p)-ß-catenin, Runt-related transcription factor 2 (Runx2) and Cyclin D1 in the femurs and/or tibias were examined by Western blot or immunohistochemical staining. The main constituents in the SJZD aqueous extract were characterized by a HPLC/MS. RESULTS: SJZD intervention improved glucose and lipid metabolism and preserved bone quality in the diabetic mice, in particular glucose tolerance, lipid profile, bone microarchitecture, strength and material composition. SJZD administration to diabetic mice preserved redox homeostasis in serum and bone marrow, and prevented an increase in AGEs, RAGE, p-NF-κB/NF-κB, cathepsin K, p-GSK-3ß, p-ß-catenin expressions and a decrease in Sema3A, IGF1, ß-catenin, Runx2 and Cyclin D1 expressions in tibias and/or femurs. Thirteen compounds were identified in SJZD aqueous extract, including astilbin, liquiritin apioside, ononin, ginsenoside Re, Rg1, Rb1, Rb2, Ro, Rb3, Rd, notoginsenoside R2, glycyrrhizic acid, and licoricesaponin B2. CONCLUSIONS: SJZD ameliorates bone quality in diabetic mice possibly via maintaining redox homeostasis. The mechanism governing these alterations are possibly related to effects on the AGEs/RAGE and Wnt/ß-catenin signaling pathways. SJZD may offer a novel source of drug candidates for the prevention and treatment of type 2 diabetes and osteoporosis.

9.
Sports Med Health Sci ; 5(3): 245-250, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37753425

RESUMO

To explore the appropriate exercise methods and means for astronauts in confined and small isolation conditions, a set of XunTian Tai Chi suitable for the spaceflight workforce was created, with the aim of discovering the practical effects of XunTian Tai Chi and providing a scientific basis for the subsequent development of new astronaut health maintenance techniques with Chinese characteristics. Using the Controlled Ecological Life Support System (CELSS) as a research platform, we observed the changes in a crew member's emotion regulation-related indexes during 180 days of working and living in a confined isolation chamber through periodic interventions of the XunTian Tai Chi and conducted statistical analyses. During the 180-day cabin mission, expression suppression, cognitive reappraisal, attention index, and relaxation index were all lower than those before entering the cabin, suggesting that the crew member's emotion regulation ability decreased during the in-cabin mission. A single Tai Chi exercise could cause favorable changes in the indicators, positively affecting the crew member's emotional regulation. The attention and relaxation indices of the occupants were improved significantly by both single and periodic Tai Chi exercises. After the Tai Chi exercise cycle, the results of each index showed a certain degree of effect. The 180-day ground-based simulation of Tai Chi in the confinement of a space capsule positively affects the occupant's emotional regulation.

10.
Br J Cancer ; 2023 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-37758837

RESUMO

BACKGROUND: To investigate the predictive ability of high-throughput MRI with deep survival networks for biochemical recurrence (BCR) of prostate cancer (PCa) after prostatectomy. METHODS: Clinical-MRI and histopathologic data of 579 (train/test, 463/116) PCa patients were retrospectively collected. The deep survival network (iBCR-Net) is based on stepwise processing operations, which first built an MRI radiomics signature (RadS) for BCR, and predicted the T3 stage and lymph node metastasis (LN+) of tumour using two predefined AI models. Subsequently, clinical, imaging and histopathological variables were integrated into iBCR-Net for BCR prediction. RESULTS: RadS, derived from 2554 MRI features, was identified as an independent predictor of BCR. Two predefined AI models achieved an accuracy of 82.6% and 78.4% in staging T3 and LN+. The iBCR-Net, when expressed as a presurgical model by integrating RadS, AI-diagnosed T3 stage and PSA, can match a state-of-the-art histopathological model (C-index, 0.81 to 0.83 vs 0.79 to 0.81, p > 0.05); and has maximally 5.16-fold, 12.8-fold, and 2.09-fold (p < 0.05) benefit to conventional D'Amico score, the Cancer of the Prostate Risk Assessment (CAPRA) score and the CAPRA Postsurgical score. CONCLUSIONS: AI-aided iBCR-Net using high-throughput MRI can predict PCa BCR accurately and thus may provide an alternative to the conventional method for PCa risk stratification.

11.
Heliyon ; 9(9): e19322, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37674829

RESUMO

Osteoarthritis (OA) is a common joint disease characterized by chronic pain, and the perception of pain is closely associated with brain function and neuropeptide regulation. Rehmannia is common plant herb with anti-inflammatory and analgesic properties that is used to treat OA. However, it is unclear whether Rehmannia alleviates OA-related pain via regulation of neuropeptides and brain function. We examined the pain relief regulatory pathway in OA after treatment with Rehmannia by verifying the therapeutic effect of Rehmannia alcohol extract in vivo and vitro and exploring of the potential mechanism underlying the analgesic effect of Rahmanian using functional magnetic resonance imaging and measuring neuropeptide secretion. Our results showed that Rehmannia alcohol extract and the related active ingredient, Rehmannioside D, can delay cartilage degradation and alleviate inflammation in OA rats. The Rehmannia alcohol extract can also relieve OA pain, reduce the secretion of calcitonin gene-related peptide (CGRP) and substance P (SP), and reverse the pathological changes in the cerebral cortex and hippocampus. Our research results demonstrate that Rehmannia alleviates OA pain by protecting cartilage, preventing the stimulation of inflammatory factors on neuropeptide secretion, and influencing the relevant functional areas of the brain.

12.
Front Genet ; 14: 1112744, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37671041

RESUMO

Background: Immunity and ferroptosis often play a synergistic role in the progression and treatment of hepatocellular carcinoma (HCC). However, few studies have focused on identifying immune-related ferroptosis gene biomarkers. Methods: We performed weighted gene co-expression network analysis (WGCNA) and random forest to identify prognostic differentially expressed immune-related genes (PR-DE-IRGs) highly related to HCC and characteristic prognostic differentially expressed ferroptosis-related genes (PR-DE-FRGs) respectively to run co-expression analysis for prognostic differentially expressed immune-related ferroptosis characteristic genes (PR-DE-IRFeCGs). Lasso regression finally identified 3 PR-DE-IRFeCGs for us to construct a prognostic predictive model. Differential expression and prognostic analysis based on shared data from multiple sources and experimental means were performed to further verify the 3 modeled genes' biological value in HCC. We ran various performance testing methods to test the model's performance and compare it with other similar signatures. Finally, we integrated composite factors to construct a comprehensive quantitative nomogram for accurate prognostic prediction and evaluated its performance. Results: 17 PR-DE-IRFeCGs were identified based on co-expression analysis between the screened 17 PR-DE-FRGs and 34 PR-DE-IRGs. Multi-source sequencing data, QRT-PCR, immunohistochemical staining and testing methods fully confirmed the upregulation and significant prognostic influence of the three PR-DE-IRFeCGs in HCC. The model performed well in the performance tests of multiple methods based on the 5 cohorts. Furthermore, our model outperformed other related models in various performance tests. The immunotherapy and chemotherapy guiding value of our signature and the comprehensive nomogram's excellent performance have also stood the test. Conclusion: We identified a novel PR-DE-IRFeCGs signature with excellent prognostic prediction and clinical guidance value in HCC.

13.
Adv Sci (Weinh) ; : e2303922, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37672883

RESUMO

As water-saturated polymer networks, hydrogels are a growing family of soft materials that have recently become promising candidates for flexible electronics application. However, it remains still difficult for hydrogel-based strain sensors to achieve the organic unity of mechanical properties, electrical conductivity, and water retention. To address this challenge, based on the template, the excellent properties of MXene nanoflakes (rich surface functional groups, high specific surface area, hydrophilicity, and conductivity) are fully utilized in this study to prepare the P(AA-co-AM)/MXene@PDADMAC semi-interpenetrating network (semi-IPN) hydrogel. The proposed hydrogel continues to exhibit excellent strain response and flexibility after 30 days of storage at room temperature, and its performance do not decrease after 1100 cycles. Considering these characteristics, a hydrogel-based device for converting sign language into Chinese characters is successfully developed and optimized using machine learning. Therefore, this study provides novel insight and application directions for hydrogel families.

14.
Vox Sang ; 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37673798

RESUMO

BACKGROUND AND OBJECTIVES: Rail logistics transmission systems (RLTSs) are commonly used for the transportation of blood samples, pathological specimens and other medical materials in many hospitals, as they are rapid, secure, cost-effective and intelligent. However, few studies have evaluated blood component transportation from blood banks to the patient care areas of hospitals using RLTS. In this study, we evaluate the RLTS used for the transportation of blood components within a medical centre. MATERIALS AND METHODS: The dispatch of blood components, including packed red blood cells (pRBCs), fresh frozen plasma (FFP), cryoprecipitate and platelet units, from a blood bank to critical care areas or general wards was done using RLTS. Parameters such as the delivery time, temperature, physical integrity and blood component quality were evaluated via analytical testing using specimens obtained before and after transportation by RLTS. RESULTS: The turnaround time and temperature of all tested blood units via RLTS transportation were able to meet the clinical demands of blood component delivery (median time: 323 s [118-668 s]; temperature variation: 4.5-8.9°C for pRBCs and FFP and 21.5-23.5°C for cryoprecipitate and platelet units). Furthermore, parameters of pRBC quality, including the haemolysis index and potassium and lactate dehydrogenase levels in plasma, were not significantly different before and after transportation through RLTS. Similarly, RLTS transportation affected neither the basic coagulation test results in FFP and cryoprecipitate specimens nor platelet aggregation and activation markers in apheresis platelet specimens. CONCLUSION: Hospital-wide delivery of blood components via RLTS seems to be safe, reliable and cost-effective and does not have any negative impact on blood quality. Therefore, the establishment of standard criteria, protocols and guidelines based on further studies is needed.

15.
Plants (Basel) ; 12(17)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37687330

RESUMO

In order to reduce sucrose content in jujube juice and prepare a jujube juice beverage rich in rare sugars, jujube juice was used as raw material for multienzyme catalysis in this study. The effects of single factors such as substrate, pH, DPE and L-RI addition ratio, enzyme treatment temperature, and metal ions on sucrose conversion and D-allulose formation in jujube juice were investigated. Changes in glucose, D-allulose, and D-allose contents in jujube juice before and after enzyme conversion were analyzed by high-performance liquid chromatography (HPLC). The results showed that 'Xiangfenmuzao' was more suitable for subsequent double enzyme coupling reactions in different varieties of jujube juice at different periods. Factors such as pH, DPE and L-RI enzyme ratio, temperature, and treatment time had significant effects on sucrose conversion and D-allulose production in 'Xiangfenmuzao' juice (p < 0.05). When the ratio of DPE and L-RI was 1:10, pH was 7.5, and the temperature was 60 °C for 7 h, the fructose content in the full-red stage jujube juice of 'Xiangfenmuzao' and 'Jinsixiaozao' decreased gradually, and the final yield was about 53%. The yield of D-allulose was about 29%, and the yield of D-allulose was about 17%. In this study, DPE and L-RI were used to treat whole red jujube juice, which could effectively reduce sucrose content in jujube juice and obtain a functional jujube juice beverage that is low in calories and rich in rare sugar.

16.
Am J Nephrol ; : 1-9, 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37708857

RESUMO

INTRODUCTION: In FIDELIO-DKD, finerenone significantly improved cardiorenal outcomes in patients with chronic kidney disease and type 2 diabetes (T2D). This post hoc analysis explores finerenone in patients from the Asian region. METHODS: In FIDELIO-DKD, 5,674 patients with T2D and urine albumin-to-creatinine ratio (UACR) ≥30-<300 mg/g and estimated glomerular filtration rate (eGFR) ≥25-<60 mL/min/1.73 m2 or UACR ≥300-≤5,000 mg/g and eGFR ≥25-<75 mL/min/1.73 m2, treated with optimized renin-angiotensin system blockade, were randomized 1:1 to finerenone or placebo. Efficacy outcomes included a primary kidney composite (time to kidney failure, sustained decrease of ≥40% in eGFR from baseline, and death from renal causes) and secondary cardiovascular (CV) (time to CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) and kidney (time to kidney failure, sustained decrease of ≥57% in eGFR from baseline, and death from renal causes) composites. RESULTS: Of 1,327 patients in the Asian subgroup, 665 received finerenone. Finerenone reduced the ≥40% and ≥57% eGFR kidney and CV composite outcomes versus placebo in the Asian subgroup (hazard ratio [HR]: 0.70; 95% confidence interval [CI]: 0.56-0.87, HR: 0.73; 95% CI: 0.55-0.97, and HR: 0.85; 95% CI: 0.59-1.21, respectively), with no apparent differences versus patients from the rest of the world (HR: 0.88; 95% CI: 0.77-1.02; p interaction 0.09, HR: 0.78; 95% CI: 0.64-0.95; p interaction 0.71, and HR: 0.86; 95% CI: 0.74-1.00; p interaction 0.95, respectively). The safety profile of finerenone was similar across subgroups. CONCLUSION: Finerenone produces similar cardiorenal benefits in Asian and non-Asian patients.

17.
J Transl Med ; 21(1): 589, 2023 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-37660053

RESUMO

BACKGROUND: The influence of the historical cardiovascular risk status on future risk of atherosclerotic cardiovascular disease (ASCVD) is poorly understood. We aimed to investigate the association between 5-year changes in cardiovascular risk and ASCVD incidence. METHODS: We analyzed pooled data from seven community-based prospective cohort studies with up to 20 years of follow-up data. The study populations included White or Black participants aged 40-75 years without prevalent ASCVD. Cardiovascular risk was assessed using the pooled cohort equation and was categorized into non-high (< 20%) or high risk (≥ 20%). Changes in cardiovascular disease (CVD) risk over a 5-year interval were recorded. The main outcome was incident ASCVD. RESULTS: Among 11,026 participants (mean [SD] age, 60.0 [8.1] years), 4272 (38.7%) were female and 3127 (28.4%) were Black. During a median follow-up period of 9.9 years, 2560 (23.2%) ASCVD events occurred. In comparison with individuals showing a consistently high CVD risk, participants whose CVD risk changed from non-high to high (hazard ratio [HR], 0.67; 95% confidence interval [CI] 0.59-0.77) or high to non-high (HR, 0.57; 95% CI 0.41-0.80) and those with a consistently non-high risk (HR, 0.33; 95% CI 0.29-0.37) had a lower risk of incident ASCVD. In comparison with individuals showing a consistently non-high CVD risk, participants whose CVD risk changed from high to non-high (HR, 1.74; 95% CI 1.26-2.41) or from non-high to high risk (HR, 2.04; 95% CI 1.84-2.27) and those with a consistently high risk (HR 3.03; 95% CI 2.69-3.42) also showed an increased risk of incident ASCVD. CONCLUSIONS: Individuals with the same current CVD risk status but different historical CVD risks exhibited varying risks of future ASCVD incidents. Dynamic risk evaluation may enable more accurate cardiovascular risk stratification, and decision-making regarding preventive interventions should take the historical risk status into account.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Incidência , Doenças Cardiovasculares/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Fatores de Risco , Aterosclerose/epidemiologia , Fatores de Risco de Doenças Cardíacas
18.
Am J Hematol ; 2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37706580

RESUMO

Anti-thymocyte globulin (ATG) is widely used in allogeneic hematopoietic stem cell transplantation to prevent severe graft-versus-host disease (GVHD) and graft failure. However, overexposure to ATG may increase cytomegalovirus (CMV), Epstein-Barr virus (EBV) reactivation, non-relapse mortality, and disease recurrence. To investigate the optimal dosing of ATG, we established a targeted dosing strategy based on ATG concentration monitoring for haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). The aim of this phase 2 trial is to evaluate the safety and efficacy of the ATG-targeted dosing strategy in adult unmanipulated haplo-PBSCT. ATG was administered for 4 days (-5 days to -2 days) during conditioning. The ATG doses on -3 days and -2 days were adjusted by our dosing strategy to achieve the optimal ATG exposure. The primary endpoint was CMV reactivation on +180 days. Between December 2020 and January 2022, 66 haplo-PBSCT patients were enrolled and 63 of them were evaluable with a median follow-up of 632 days. The cumulative incidence of CMV reactivation was 36.7% and that of EBV was 58.7%. The 1-year disease-free survival was 82.5%, overall survival was 92.1%, and CD4+ T-cell reconstruction on +100 days was 76.8%. The most common severe regimen-associated toxicities (> grade 3) were infections (51.5%) and gastrointestinal toxicity (25.5%). A total of 102 haplo-PBSCT patients who received the conventional fixed ATG dose (cumulative 10 mg/kg) comprised historical control. The outcomes in historical control were inferior to those of phase 2 trial cohort (CMV reactivation: 70.8%, p < .001; EBV reactivation: 76.0%, p = .024; CD4 + T-cell reconstruction: 54.1%, p = .040). In conclusion, ATG-targeted dosing strategy reduced CMV/EBV reactivation and improved survival without increasing GVHD after haplo-PBSCT. These advantages may be associated with accelerated immune reconstitution.

19.
Sci Total Environ ; 903: 166953, 2023 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-37699480

RESUMO

Microplastics (MPs) are plastic fragments with particle sizes <5 mm, ubiquitously distributed in terrestrial environments. However, the negative effects of MPs, such as joint-pollution with heavy metals on soil fauna remain controversial. This study investigated survival rate, growth, reproduction, avoidance behavior, histology, biochemical assays, comet assay, qPCR, Cd content, and IBR index. We found that six types of traditional MPs (PC, PP, PVC, LDPE, PET and PS, and PLA (a biodegradable microplastics)) had no adverse effects on earthworm growth, survival and reproduction. Moreover, we found that earthworms exhibit an avoidance behavior towards PLA. Both PS and PLA can exacerbated Cd pollution, leading to loose circular muscle layer, DNA damage in coelomocytes, and impaired antioxidant system due to increased reactive oxygen species (ROS). mRNA level of HSP70 increased under joint-pollution of both PS and Cd or PLA and Cd compared to Cd treatment alone. MPs enhanced Cd accumulation in earthworms in Cd-contaminated soil. Notably, the Integrated Biomarkers Response index revealed that the toxicity of joint PLA and Cd was greater than the joint effect of PS and Cd, which might violate the original intention of biodegradable plastics having non-toxic influence on the soil fauna. Our findings provide new insights into the ecotoxicological effects of MPs, the joint ecotoxicological effects of MPs and Cd on earthworms, and the ecological risks of MPs to soil fauna.

20.
Anal Chim Acta ; 1278: 341704, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37709448

RESUMO

Covalent sensors to detect and capture aggregated proteome in stressed cells are rare. Herein, we construct a series of covalent fluorogenic sensors for aggregated proteins by structurally modulating GFP chromophore and arming it with an epoxide warhead. Among them, P2 probe selectively modifies aggregated proteins over folded ones and turns on fluorescence as evidenced by biochemical and mass spectrometry results. The coverage of this epoxide-based covalent chemistry is demonstrated using different types of aggregated proteins. Finally, the covalent fluorescent sensor P2 allows for direct visualization and capture of aggregated proteome in stressed cardiomyocytes and cardiac tissue samples from a cardio-oncology mouse model. The epoxide-based covalent sensor developed herein may become useful for future chemical proteomics analysis of aggregated proteins to dissect the mechanism underlying cardio-oncology.


Assuntos
Neoplasias , Proteoma , Animais , Camundongos , Cromatografia Gasosa-Espectrometria de Massas , Coração , Compostos de Epóxi
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