Comprehensive Glycosylation Characterization of Recombinant Human Erythropoietin by Electron-Activated Dissociation Mass Spectrometry.

Recombinant human erythropoietin (rhEPO) is a glycoprotein that acts as the main hormone involved in regulating red blood cell production to treat anemia caused by chronic kidney disease or chemotherapy, which has three N-glycosylation sites and one O-glycosylation site. It contains a variety of different glycosylation modifications, such as sialyation, O-acetylation on sialic acids, etc., which causes a big challenge for the glycosylation analysis of rhEPO. In this study, a liquid chromatography-mass spectrometry (LC-MS) method combined with electron-activated dissociation (EAD) technology was used in qualitative and quantitative characterization of rhEPO N-glycosylation and O-glycosylation in just one injection. The usage of EAD not only generated abundant MS/MS fragment ions of glycopeptides and improved the MS/MS sequence coverage but also preserved the glycan structures in the MS/MS fragment ions and the integrity of the glycosidic bond between the glycans and peptides. Three N-glycosylation sites (N24, N38, and N83) and one O-glycosylation site (S126) of rhEPO samples were successfully identified. Among them, the glycosylation ratios of N24, N38, and N83 sites were 82.7%, 100%, and 100% respectively, and 15, 10, and 12 different N-glycans could be identified at the glycopeptide level. The total average number of sialic acids, N-hydroxyacetylneuraminoic acid, and O-acetylation on sialic acid were 7.28, 4.21, and 0.66 at the intact protein level, respectively. For O-glycosylation site S126, O-glycosylation ratios analyzed at the intact protein level and the glycopeptide level were 80.2% and 80.3%, respectively, and two O-glycans were identified, including Core1_S1 and Core1_S2. This study also compared the difference of the glycans and their relative contents in batch-to-batch rhEPO samples. The results proved that the workflow using EAD fragmentation in LC-MS method could be effectively applied for characterizing the glycosylation analysis of rhEPO samples and batch-to-batch consistency analysis, which would help to reasonably guide the optimization of rhEPO production process.

Repair effect of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles on ovarian injury induced by cisplatin.

Small extracellular vesicles (sEVs) secreted by human umbilical cord have therapeutic effects on various degenerative diseases. However, the characteristics and potential functions of human umbilical cord mesenchymal stem cells (huMSCs)-derived sEVs, especially the role of premature ovarian failure (POF), are poorly understood. Here, we isolated and characterized huMSCs and their sEVs. huMSCs highly expressed CD73, CD90, and CD105. huMSC-sEVs showed typical exosomal features, highly expressing CD9, TSG101, and CD63. It was shown that huMSC-sEVs could be taken up by granulosa cells (GCs) and damaged ovarian tissue, which increased the levels of hormone secretion and reduced GCs apoptosis. We further confirmed that the levels of follicle-stimulating hormone in rat serum decreased dramatically, while the levels of estrogen (E2）and anti-mullerian hormone (AMH) increased significantly with the treatment of huMSC-sEVs. Meanwhile, huMSC-sEVs treatment greatly reduced cell apoptosis and autophagy, while increased the phosphorylation levels of p-PI3K and p-Akt. Therefore, treatment with huMSC-sEVs significantly inhibited GCs apoptosis, improved ovarian morphology, promoted follicular development, inhibited follicular over-atresia, and improved ovarian reserve capacity in POF rats. Our study verified that activation of PI3K/Akt signaling pathway and regulation of cellular autophagy, thus reducing GCs death, are the mechanisms by which huMSC-sEVs restore ovarian tissue function.

Multi-omics analysis provides new insights into the changes of important nutrients and fructose metabolism in loquat bud sport mutant.

Bud sport is a common and stable somatic variation in perennial fruit trees, and often leads to significant modification of fruit traits and affects the breeding value. To investigate the impact of bud sport on the main metabolites in the fruit of white-fleshed loquat, we conducted a multi-omics analysis of loquat fruits at different developmental stages of a white-fleshed bud sport mutant of Dongting loquat (TBW) and its wild type (TBY). The findings from the detection of main fruit quality indices and metabolites suggested that bud sport resulted in a reduction in the accumulation of carotenoids, fructose, titratable acid and terpenoids at the mature stage of TBW, while leading to the accumulation of flavonoids, phenolic acids, amino acids and lipids. The comparably low content of titratable acid further enhances the balanced and pleasent taste profile of TBW. Expression patterns of differentially expressed genes involved in fructose metabolism exhibited a significant increase in the expression level of S6PDH (EVM0006243, EVM0044405) prior to fruit maturation. The comparison of protein sequences and promoter region of S6PDH between TBY and TBW revealed no structural variations that would impact gene function or expression, indicating that transcription factors may be responsible for the rapid up-regulation of S6PDH before maturation. Furthermore, correlation analysis helped to construct a comprehensive regulatory network of fructose metabolism in loquat, including 23 transcription factors, six structural genes, and nine saccharides. Based on the regulatory network and existing studies, it could be inferred that transcription factors such as ERF, NAC, MYB, GRAS, and bZIP may promote fructose accumulation in loquat flesh by positively regulating S6PDH. These findings improve our understanding of the nutritional value and breeding potential of white-fleshed loquat bud sport mutant, as well as serve as a foundation for exploring the genes and transcription factors that regulate fructose metabolism in loquat.

Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy.

Despite decades of laboratory and clinical trials, breast cancer remains the main cause of cancer-related disease burden in women. Considering the metabolism destruction effect of metformin (Met) and cancer cell starvation induced by glucose oxidase (GOx), after their efficient delivery to tumor sites, GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ. Herein, a pH-responsive epigallocatechin gallate (EGCG)-conjugated low-molecular-weight chitosan (LC-EGCG, LE) nanoparticle (Met-GOx/Fe@LE NPs) was constructed. The coordination between iron ions (Fe3+) and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction. Met-GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability. Moreover, this pH-responsive nanoplatform presents controllable drug release behavior. An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free drug. The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation. This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

Adding carbon sources to the substrates enhances Cr and Ni removal and mitigates greenhouse gas emissions in constructed wetlands.

Constructed wetlands for wastewater treatment pose challenges related to long-term operational efficiency and greenhouse gas emissions on a global scale. This study investigated the impact of adding peat, humic acid, and biochar into the substrates of constructed wetlands and focused on Cr, and Ni removal, greenhouse gas emissions, and microbial communities in constructed wetlands. Biochar addition treatment achieved the highest removal efficiencies for total Cr (99.96%), Cr (VI) (100%), and total Ni (91.04%). Humic acid and biochar addition both significantly increased the heavy metal content in wetland plant Leersia hexandra and substrates of constructed wetlands. Further analysis of microbial community proportions by high-throughput sequencing revealed that biochar and humic acid treatments enhanced Cr and Ni removal efficiency by increasing the abundance of Bacteroidetes, Geobacter and Ascomycota. Humic acid addition treatment reduced CO2 emissions by decreasing the abundance of Bacteroidetes and increasing that of Basidiomycota. Peat treatment decreased CH4 emissions by reducing the abundance of the Bacteroidetes. Biochar treatment increased the abundance of the Firmicutes, Bacteroidetes, Proteobacteria as well as Basidiomycota, resulting in reduced N2O emissions. Biochar and humic acid treatments efficiently removed heavy metals from wastewater and mitigated greenhouse gas emissions in constructed wetlands by modifying the microbial communities.

U-shaped relationship between lights-out time and nocturnal oxygen saturation during the first trimester: An analysis based on the nuMOM2b-SDB data.

Objective: Preventing adverse events due to unstable oxygen saturation (SpO2) at night in pregnant women is of utmost importance. Poor sleep has been demonstrated to impact SpO2 levels. Nowadays, many gravida have a habit of prolonged exposure to light before sleep, which can disrupt their sleep. Therefore, this study aimed at investigate the relationship between lights-out time, sleep parameters and SpO2, exploring the underlying mechanisms. Methods: The data of 2881 eligible subjects from the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be and Sleep Disordered Breathing (nuMOM2b-SDB) database were analyzed. Multiple linear regression models were used to investigate the relationship between lights-out time and SpO2. In addition, restricted cubic splines (RCS) were employed to fit the nonlinear correlation between the two variables. The smoothing curve method was further utilized to depict the relationship between lights-out time and SpO2 based on various subgroup variables. Results: All participants were categorized according to race/ethnicity. A negative correlation was observed between nighttime lights-out time and average value of SpO2 (Avg-SpO2) (ß = -0.05, p = 0.010). RCS revealed a U-shaped relationship between lights-out time and Avg-SpO2, with the turning point at 22:00. The subcomponent stratification results indicated that the Avg-SpO2 and minimum value of SpO2(Min-SpO2) of advanced maternal age decreased as the lights-out time was delayed. Furthermore, overweight and obese gravida showed lower Avg-SpO2 and Min-SpO2 levels than normal weight. Conclusions: A U-shaped relationship was identified between lights-out time and nocturnal Avg-SpO2 during early pregnancy, with the inflection at 22:00. Notably, later lights-out times are associated with lower levels of Min-SpO2 for advanced maternal age. The findings suggest that appropriately adjusting the duration of light exposure before sleep and maintaining a relatively restful state may be more beneficial for the stability of SpO2 in pregnant women. Conversely, deviations from these practices could potentially lead to pathological alterations in SpO2 levels.

Correlation Between Prefrontal Functional Connectivity and the Degree of Cognitive Impairment in Alzheimer's Disease: A Functional Near-Infrared Spectroscopy Study.

Background: The development of Alzheimer's disease (AD) can be divided into subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia. Early recognition of pre-AD stages may slow the progression of dementia. Objective: This study aimed to explore functional connectivity (FC) changes of the brain prefrontal cortex (PFC) in AD continuum using functional near-infrared spectroscopy (fNIRS), and to analyze its correlation with cognitive function. Methods: All participants underwent 48-channel fNIRS at resting-state. Based on Brodmann partitioning, the PFC was divided into eight subregions. The NIRSIT Analysis Tool (v3.7.5) was used to analyze mean ΔHbO2 and FC. Spearman correlation analysis was used to examine associations between FC and cognitive function. Results: Compared with HC group, the mean ΔHbO2 and FC were different between multiple subregions in the AD continuum. Both mean ΔHbO2 in the left dorsolateral PFC and average FC decreased sequentially from SCD to MCI to AD groups. Additionally, seven pairs of subregions differed in FC among the three groups: the differences between the MCI and SCD groups were in heterotopic connectivity; the differences between the AD and SCD groups were in left intrahemispheric and homotopic connectivity; whereas the MCI and AD groups differed only in homotopic connectivity. Spearman correlation results showed that FCs were positively correlated with cognitive function. Conclusions: These results suggest that the left dorsolateral PFC may be the key cortical impairment in AD. Furthermore, there are different resting-state prefrontal network patterns in AD continuum, and the degree of cognitive impairment is positively correlated with reduced FC strength.

Sweet cherry TCP gene family analysis reveals potential functions of PavTCP1, PavTCP2 and PavTCP3 in fruit light responses.

BACKGROUND: TCP proteins are plant specific transcription factors that play important roles in plant growth and development. Despite the known significance of these transcription factors in general plant development, their specific role in fruit growth remains largely uncharted. Therefore, this study explores the potential role of TCP transcription factors in the growth and development of sweet cherry fruits. RESULTS: Thirteen members of the PavTCP family were identified within the sweet cherry plant, with two, PavTCP1 and PavTCP4, found to contain potential target sites for Pav-miR159, Pav-miR139a, and Pav-miR139b-3p. Analyses of cis-acting elements and Arabidopsis homology prediction analyses that the PavTCP family comprises many light-responsive elements. Homologs of PavTCP1 and PavTCP3 in Arabidopsis TCP proteins were found to be crucial to light responses. Shading experiments showed distinct correlation patterns between PavTCP1, 2, and 3 and total anthocyanins, soluble sugars, and soluble solids in sweet cherry fruits. These observations suggest that these genes may contribute significantly to sweet cherry light responses. In particular, PavTCP1 could play a key role, potentially mediated through Pav-miR159, Pav-miR139a, and Pav-miR139b-3p. CONCLUSION: This study is the first to unveil the potential function of TCP transcription factors in the light responses of sweet cherry fruits, paving the way for future investigations into the role of this transcription factor family in plant fruit development.

Characterization of Adeno-Associated Virus Capsid Proteins by Microflow Liquid Chromatography Coupled with Mass Spectrometry.

Adeno-associated virus (AAV) has been widely used to treat various human diseases as an important delivery vector for gene therapy due to its low immunogenicity and safety. AAV capsids proteins are comprised of three capsid viral proteins (VP; VP1, VP2, VP3). The capsid proteins play a key role in viral vector infectivity and transduction efficiency. To ensure the safety and efficacy of AAV gene therapy products, the quality of AAV vector capsid proteins during development and production should be carefully monitored and controlled. Microflow liquid chromatography coupled with mass spectrometry provides superior sensitivity and fast analysis capability. It showed significant advantages in the analysis of low- concentration and large numbers of AAV samples. The intact mass of capsid protein can be accurately determined using high-resolution mass spectrometry (MS). And MS also provides highly confident confirmation of sequence coverage and post-translational modifications site identification and quantitation. In this study, we used microflow liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the characterization of AAV2 capsid protein. we obtained nearly 100% sequence coverage of low-concentration AAV2 capsid protein (8 × 1011 GC/mL). More than 30 post-translational modifications (PTMs) sites were identified, the PTMs types included deamidation, oxidation and acetylation. From this study, the proposed microflow LC-MS/MS method provides a sensitive and high throughput approach in the characterization of AAVs and other biological products with low abundance.

Analysis of full and empty ratio of EV71 virus by using capillary zone electrophoresis.

Hand, foot, and mouth disease is a serious public health problem, and the main pathogen is enterovirus 71 (EV71). Its capsid assembly mechanism including capsid protein processing has been widely studied. Full and empty capsids have different immunological efficacy. Therefore, tracking full/empty capsid ratio throughout the EV71 production process is important to ensure consistent product quality and proper dosing response. The analysis of full/empty capsid ratio of intact virus has been widely reported as well. A variety of techniques have been employed to evaluate the full/empty capsid ratios. However, there has not been a rapid, reproducible, and robust assay to determine the full/empty capsid ratios of final and in-process products. In this study, a novel assay based on capillary zone electrophoresis was established. The separation of full and empty species could be achieved within 10 min and the ratio of peak areas was used to calculate the full/empty capsid ratio directly. The results showed good reproducibility and linearity for the determination of full/empty capsid ratios.

Application of bacterial agent YH for remediation of pyrene-heavy metal co-pollution system: Efficiency, mechanism, and microbial response.

The combination of organic and heavy metal pollutants can be effectively and sustainably remediated using bioremediation, which is acknowledged as an environmentally friendly and economical approach. In this study, bacterial agent YH was used as the research object to explore its potential and mechanism for bioremediation of pyrene-heavy metal co-contaminated system. Under the optimal conditions (pH 7.0, temperature 35°C), it was observed that pyrene (PYR), Pb(II), and Cu(II) were effectively eliminated in liquid medium, with removal rates of 43.46%, 97.73% and 81.60%, respectively. The microscopic characterization (SEM/TEM-EDS, XPS, XRD and FTIR) results showed that Pb(II) and Cu(II) were eliminated by extracellular adsorption and intracellular accumulation of YH. Furthermore, the presence of resistance gene clusters (cop, pco, cus and pbr) plays an important role in the detoxification of Pb(II) and Cu(II) by strains YH. The degradation rate of PYR reached 72.51% in composite contaminated soil, which was 4.33 times that of the control group, suggesting that YH promoted the dissipation of pyrene. Simultaneously, the content of Cu, Pb and Cr in the form of F4 (residual state) increased by 25.17%, 6.34% and 36.88%, respectively, indicating a decrease in the bioavailability of heavy metals. Furthermore, YH reorganized the microbial community structure and enriched the abundance of hydrocarbon degradation pathways and enzyme-related functions. This study would provide an effective microbial agent and new insights for the remediation of soil and water contaminated with organic pollutants and heavy metals.

State-of-the-art electrochemical biosensors based on covalent organic frameworks and their hybrid materials.

As the development of global population and industry civilization, the accurate and sensitive detection of intended analytes is becoming an important and great challenge in the field of environmental, medical, and public safety. Recently, electrochemical biosensors have been constructed and used in sensing fields, such as antibiotics, pesticides, specific markers of cancer, and so on. Functional materials have been designed and prepared to enhance detection performance. Among all reported materials, covalent organic frameworks (COFs) are emerging as porous crystalline materials to construct electrochemical biosensors, because COFs have many unique advantages, including large surface area, high stability, atom-level designability, and diversity, to achieve a far better sensing performance. In this comprehensive review, we not only summarize state-of-the-art electrochemical biosensors based on COFs and their hybrid materials but also highlight and discuss some typical examples in detail. We finally provide the challenge and future perspective of COFs-based electrochemical biosensors.

Risk Factor Analysis and Nomogram for Predicting In-Hospital Mortality in ICU Patients with Heat Stroke: A National Multicenter Study.

Objective: The aim of this nationwide multicenter study was to ascertain the risk factors associated with in-hospital mortality in patients with heat stroke admitted to intensive care units (ICUs) and to develop a nomogram for prognostic prediction. Methods: A retrospective analysis was conducted on clinical data collected from ICU patients diagnosed with heat stroke across multiple centers nationwide. Univariate and multivariate logistic regression analyses were performed to identify significant risk factors for in-hospital mortality. Based on the results of the multivariate analysis, a nomogram was constructed to estimate the individualized probability of mortality. Internal validation of the nomogram was performed, and its performance was assessed using receiver operating characteristic (ROC) curves, calibration plots, and decision curve analysis (DCA). Results: A total of 292 ICU patients with heat stroke were included in this study. Three risk factors, namely Cr (creatinine), AST (aspartate aminotransferase), and SBP (systolic blood pressure), were found to be significantly associated with in-hospital mortality. These risk factors were incorporated into the nomogram, which exhibited good discriminative ability (area under the ROC curve of the training and validation cohorts were 0.763 and 0.739, respectively) and calibration. Internal validation and decision curve analysis confirmed the stability and reliability of the nomogram. Conclusion: This nationwide multicenter study identified key risk factors for in-hospital mortality in ICU patients with heat stroke. The developed nomogram provides an individualized prediction of mortality risk and can serve as a valuable tool for clinicians in the assessment and management of ICU patients with heat stroke.

Potential regulatory genes of light induced anthocyanin accumulation in sweet cherry identified by combining transcriptome and metabolome analysis.

Anthocyanins exist widely in various plant tissues and organs, and they play an important role in plant reproduction, disease resistance, stress resistance, and protection of human vision. Most fruit anthocyanins can be induced to accumulate by light. Here, we shaded the "Hong Deng" sweet cherry and performed an integrated analysis of its transcriptome and metabolome to explore the role of light in anthocyanin accumulation. The total anthocyanin content of the fruit and two of its anthocyanin components were significantly reduced after the shading. Transcriptome and metabolomics analysis revealed that PAL, 4CL, HCT, ANS and other structural genes of the anthocyanin pathway and cyanidin 3-O-glucoside, cyanidin 3-O-rutinoside, and other metabolites were significantly affected by shading. Weighted total gene network analysis and correlation analysis showed that the upstream and middle structural genes 4CL2, 4CL3, and HCT2 of anthocyanin biosynthesis may be the key genes affecting the anthocyanin content variations in fruits after light shading. Their expression levels may be regulated by transcription factors such as LBD, ERF4, NAC2, NAC3, FKF1, LHY, RVE1, and RVE2. This study revealed for the first time the possible role of LBD, FKF1, and other transcription factors in the light-induced anthocyanin accumulation of sweet cherry, thereby laying a preliminary foundation for further research on the role of light in anthocyanin accumulation of deep red fruit varieties and the genetic breeding of sweet cherry.

An electrochemical impedimetric platform formed by a CNT@UiO-66 nanocomposite for quantitative analysis of oxytetracycline.

Functional materials are considered one of the most critical factors in constructing high-performance electrochemical aptasensors in the sensing field. In this work, the microporous Zr-MOF UiO-66 (UiO = Universitetet i Oslo) is selected for assembly with carbon nanotubes (CNTs) to prepare a CNT@UiO-66 composite. The as-synthesized CNT@UiO-66 composite has a high surface area, excellent stability, good electrical conductivity, and abundant Zr(IV) sites, conferring it great potential for application in fabricating high-performance electrochemical aptasensors. It is gratifying that this electrochemical impedimetric aptasensor can detect trace oxytetracycline (OTC) from 0.01 to 0.7 pg mL-1 with a low limit of detection (LOD) of 1.48 fg mL-1. Meanwhile, this fabricated sensor based on CNT@UiO-66 has fine stability, excellent selectivity, and available reproducibility. In particular, the CNT@UiO-66-based aptasensor can quantitatively detect the OTC concentration in real samples.

Aripiprazole combined with nerve growth factor improves cognitive function in mice with schizophrenia model.

The pathogenesis and treatment of cognitive dysfunction in patients with schizophrenia (SCZ) remains a challenge. Exploring new effective treatment strategies is relevant for the improvement of cognitive function. Aripiprazole (ARI) is an atypical antipsychotic that improves some cognitive functions. Nerve growth factor (NGF) has been shown to improve cognitive function in certain neurological impairments and partial neurological deficits, but its mechanism of action in cognitive dysfunction in SCZ is unclear. In this study, we established schizophrenia mouse model with dizocilpine (MK-801); treated mice with ARI alone or in combination with NGF; assessed spontaneous activity and cognitive function using open field test and Morris water maze test; and measured brain-derived neurotrophic factor (BDNF) protein and mRNA expression levels using immunohistochemistry and molecular biology assays. The results showed that ARI alone or in combination with NGF can improve increased spontaneous activity and spatial learning memory deficits in model mice by elevating BDNF expression levels in prefrontal cortex (PFC) and hippocampus (HIP). The results suggest that ARI combined with NGF can improve cognitive function in SCZ, which provides new ideas and directions for the clinical treatment of cognitive dysfunction in SCZ.

Procalcitonin as a biomarker of nosocomial pneumonia in aneurysmal subarachnoid hemorrhage patients treated in neuro-ICU.

BACKGROUND: Nosocomial pneumonia commonly develops in aneurysmal subarachnoid hemorrhage (aSAH) patients and is associated with poor prognosis of these patients. This study is designed to verify the predictive value of procalcitonin (PCT) on nosocomial pneumonia in aSAH patients. METHODS: 298 aSAH patients received treatments in the neuro-intensive care unit (NICU) of West China hospital were included. Logistic regression was conducted to verify the association between PCT level and nosocomial pneumonia and to construct a model for predicting pneumonia. Area under the receiver operating characteristic curve (AUC) were calculated to evaluate the accuracy of the single PCT and the constructed model. RESULTS: 90 (30.2%) patients developed pneumonia during hospitalizations among included aSAH patients. Pneumonia group had higher procalcitonin level (p < 0.001) than non-pneumonia group. The mortality (p < 0.001), mRS (p < 0.001), length of ICU stay (p < 0.001), length of hospital stay (p < 0.001) were both higher or longer in pneumonia group. Multivariate logistic regression indicated WFNS (p = 0.001), acute hydrocephalus (p = 0.007), WBC (p = 0.021), PCT (p = 0.046) and C-reactive protein (CRP) (p = 0.031) were independently associated with the development of pneumonia in included patients. The AUC value of procalcitonin for predicting nosocomial pneumonia was 0.764. Composed of WFNS, acute hydrocephalus, WBC, PCT and CRP, the predictive model for pneumonia has higher AUC of 0.811. CONCLUSIONS: PCT is an available and effective predictive marker of nosocomial pneumonia in aSAH patients. Composed of WFNS, acute hydrocephalus, WBC, PCT and CRP, our constructed predictive model is helpful for clinicians to evaluate the risk of nosocomial pneumonia and guide therapeutics in aSAH patients.

Serum cystatin C is correlated with mortality of traumatic brain injury patients partially mediated by acute kidney injury.

BACKGROUND: Evaluating risk of poor outcome for Traumatic Brain Injury (TBI) in early stage is necessary to make treatment strategies and decide the need for intensive care. This study is designed to verify the prognostic value of serum cystatin C in TBI patients. METHODS: 415 TBI patients admitted to West China hospital were included. Logistic regression was performed to explore risk factors of mortality and testify the correlation between cystatin C and mortality. Mediation analysis was conducted to test whether Acute Kidney Injury (AKI) and brain injury severity mediate the relationship between cystatin C level and mortality. Area under the receiver operating characteristic curve (AUC) was used to evaluate the prognostic value of cystatin C and the constructed model incorporating cystatin C. RESULTS: The mortality rate of 415 TBI patients was 48.9%. Non-survivors had lower GCS (5 vs 8, p < 0.001) and higher cystatin C (0.92 vs 0.71, p < 0.001) than survivors. After adjusting confounding effects, multivariate logistic regression indicated GCS (p < 0.001), glucose (p < 0.001), albumin (p = 0.009), cystatin C (p < 0.001) and subdural hematoma (p = 0.042) were independent risk factors of mortality. Mediation analysis showed both AKI and brain injury severity exerted mediating effects on relationship between cystatin C and mortality of included TBI patients. The AUC of combining GCS with cystatin C was 0.862, which was higher than that of GCS alone (Z = 1.7354, p < 0.05). CONCLUSION: Both AKI and brain injury severity are mediating variables influencing the relationship between cystatin C and mortality of TBI patients. Serum cystatin C is an effective prognostic marker for TBI patients.

Genome-Wide Identification of Histone Deacetylases and Their Roles Related with Light Response in Tartary Buckwheat (Fagopyrum tataricum).

Histone deacetylases (HDACs), known as histone acetylation erasers, function crucially in plant growth and development. Although there are abundant reports focusing on HDACs of Arabidopsis and illustrating their important roles, the knowledge of HDAC genes in Tartary buckwheat (Polygonales Polygonaceae Fagopyrum tataricum (L.) Gaertn) is still scarce. In the study, a total of 14 HDAC genes were identified and divided into three main groups: Reduced Potassium Dependency-3/His-52 tone Deacetylase 1 (RPD3/HDA1), Silent Information Regulator 2 (SIR2), and the plant-53 specific HD2. Domain and motif composition analysis showed there were conserved domains and motifs in members from the same subfamilies. The 14 FtHDACs were distributed asymmetrically on 7 chromosomes, with three segmental events and one tandem duplication event identified. The prediction of the cis-element in promoters suggested that FtHDACs probably acted in numerous biological processes including plant growth, development, and response to environmental signals. Furthermore, expression analysis based on RNA-seq data displayed that all FtHDAC genes were universally and distinctly expressed in diverse tissues and fruit development stages. In addition, we found divergent alterations in FtHDACs transcript abundance in response to different light conditions according to RNA-seq and RT-qPCR data, indicating that five FtHDACs might be involved in light response. Our findings could provide fundamental information for the HDAC gene family and supply several targets for future function analysis of FtHDACs related with light response of Tartary buckwheat.

Exosomes derived from human umbilical cord mesenchymal stem cells alleviate Parkinson's disease and neuronal damage through inhibition of microglia.

Microglia-mediated inflammatory responses have been shown to play a crucial role in Parkinson's disease. In addition, exosomes derived from mesenchymal stem cells have shown anti-inflammatory effects in the treatment of a variety of diseases. However, whether they can protect neurons in Parkinson's disease by inhibiting microglia-mediated inflammatory responses is not yet known. In this study, exosomes were isolated from human umbilical cord mesenchymal stem cells and injected into a 6-hydroxydopamine-induced rat model of Parkinson's disease. We found that the exosomes injected through the tail vein and lateral ventricle were absorbed by dopaminergic neurons and microglia on the affected side of the brain, where they repaired nigral-striatal dopamine system damage and inhibited microglial activation. Furthermore, in an in vitro cell model, pretreating lipopolysaccharide-stimulated BV2 cells with exosomes reduced interleukin-1ß and interleukin-18 secretion, prevented the adoption of pyroptosis-associated morphology by BV2 cells, and increased the survival rate of SH-SY5Y cells. Potential targets for treatment with human umbilical cord mesenchymal stem cells and exosomes were further identified by high-throughput microRNA sequencing and protein spectrum sequencing. Our findings suggest that human umbilical cord mesenchymal stem cells and exosomes are a potential treatment for Parkinson's disease, and that their neuroprotective effects may be mediated by inhibition of excessive microglial proliferation.