Construction of a prognostic model for hepatocellular carcinoma patients receiving transarterial chemoembolization treatment based on the Tumor Burden Score.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) may have varied outcomes based on their liver function and tumor burden diversity. This study aims to assess the prognostic significance of the tumor burden score (TBS) in these patients and develop a prognostic model for their overall survival. METHODS: The study involved a retrospective analysis of 644 newly diagnosed HCC patients undergoing TACE treatment. The individuals were assigned randomly to a training cohort (n = 452) and a validation cohort (n = 192). We utilized a multivariate Cox proportional risk model to identify independent preoperative predictive factors. We then evaluated model performance using the area under the curve (AUC), consistency index (c-index), calibration curve, and decision curve analysis (DCA) methods. RESULTS: The multivariate analysis revealed four prognostic factors associated with overall survival: Tumor Burden Score, Tumor Extent, Types of portal vein invasion (PVI), and Child-Pugh score. The total score was calculated based on these factors. The model demonstrated strong discriminative ability with high AUC values and c-index, providing high net clinical benefits for patients. Based on the model's scoring results, patients were categorized into high, medium, and low-risk groups. These results were validated in the validation cohort. CONCLUSIONS: The tumor burden score shows promise as a viable alternative prognostic indicator for assessing tumor burden in cases of HCC. The new prognostic model can place patients in one of three groups, which will estimate their individual outcomes. For high-risk patients, it is suggested to consider alternative treatment options or provide the best supportive care, as they may not benefit significantly from TACE treatment.

Femtosecond Laser Combined with Hydrothermal Method to Construct Three-Dimensional Spatially Distributed Wurtzite ZnO Micro/Nanostructures to Enhance Photocatalytic Properties.

Conventional approaches employing nanopowder particles or deposition photocatalytic nanofilm materials encounter challenges such as performance instability, susceptibility to detachment, and recycling complications in practical photocatalytic scenarios. In this study, a novel fabrication strategy is proposed that uses femtosecond laser direct writing of self-sourced metal to prepare a self-supporting microstructure substrate and combines the hydrothermal method to construct a three-dimensional spatially distributed metal oxide micro/nanostructure. The obtained wurtzite ZnO micro/nanostructure has excellent wetting properties while obtaining a larger specific surface area and can achieve effective adsorption of methyl orange molecules. Moreover, the tight integration of ZnO with the surface interface of the self-sourced metal microstructure substrate will facilitate efficient charge transfer. Simultaneously, it improves the efficiency of light utilization (absorption) and the number of active sites in the photocatalytic process, ultimately leading to excellent photodegradation stability. This result provides an innovative technology solution for achieving efficient semiconductor surface-interface photocatalytic performance and stability.

The mTORC1 pathway participate in hyper-function of B cells in immune thrombocytopenia.

B cell hyper-function plays an important role in the pathogenesis of immune thrombocytopenia (ITP), but the molecular mechanisms underlying such changes remain unclear. We sought to identify regulators of B cell dysfunction in ITP patients through transcriptome sequencing and the use of inhibitors. B cells were isolated from PBMC of 25 ITP patients for B cell function test and transcriptome sequencing. For the potential regulatory factors identified by transcriptome sequencing, the corresponding protein inhibitors were used to explore the regulatory effect of the regulatory factors on B cell dysfunction in vitro. In this study, increased antibody production, enhanced terminal differentiation and highly expressed costimulatory molecules CD80 and CD86 were found in B cells of patients with ITP. In addition, RNA sequencing revealed highly activated mTOR pathway in these pathogenic B cells, indicating that the mTOR pathway may be involved in B cell hyper-function. Furthermore, mTOR inhibitors rapamycin or Torin1 effectively blocked the activation of mTORC1 in B cells, resulting in reduce antibody secretion, impaired differentiation of B cells into plasmablasts and downregulation of costimulatory molecules. Interestingly, as an unspecific inhibitor of mTORC2 besides mTORC1, Torin1 did not show a stronger capacity to modulate B cell function than rapamycin, suggesting that the regulation of B cells by Torin1 may depend on blockade of mTORC1 rather than mTORC2 pathway. These results indicated that the activation of mTORC1 pathway is involved in B cell dysfunction in patients with ITP, and inhibition of mTORC1 pathway might be a potential therapeutic approach for ITP.

Deciphering the chemical composition of Ganoderma lucidum from different geographical origins by mass spectrometry molecular networking coupled with multivariate analysis.

Ganoderma lucidum is a medicinal fungus that has been widely used in China and many Asian countries for thousands of years. This once rare macrofungus has now been artificially cultivated in a number of regions in China. However, detailed knowledge of its composition across different geographical origins is still lacking, as are analytical methods for comprehensive profiling of the diverse phytochemicals contained in G. lucidum. In this work, an on-demand strategy based on high-resolution MS and molecular networking is applied for natural product characterization, which led to the identification of 84 constituents in G. lucidum. Moreover, multivariate analysis, including hierarchical cluster analysis and orthogonal partial least squares-discriminant analysis, was used to analyze the (dis)similarity of the G. lucidum samples collected from the three main production areas (i.e., Jilin, Henan and Shandong Province). The results revealed a significant variation in the chemical composition of samples from different provinces. Marker constituents corresponding to the differentiation were then screened in terms of the variable importance in projection value, P-value and fold change. A total of 24 constituents were identified as geoherbalism markers, such as ganoderenic acid A for Henan, ganolucidic acid B for Jilin and ganodernoid D for Shandong. This proof-of-concept application demonstrates that combining MS molecular networking with meticulous multivariate analysis can provide a sensitive and comprehensive analytical approach for the quality assessment of traditional Chinese medicine ingredients. This study also suggests that the bioactivity and efficacy from different origins should be further evaluated considering the large difference in chemical compositions.

Differing postural control patterns in individuals with bilateral and unilateral hearing loss.

OBJECTIVES: Hearing loss (HL) is associated with imbalance and increased fall risk. The mechanism underlying this relationship and differences across types of hearing loss remains unclear. Head mounted displays (HMD) can shed light on postural control mechanisms via an analysis of head sway. PURPOSE: The purpose of this study was to evaluate head sway in response to sensory perturbations in individuals with bilateral (BHL) or unilateral hearing loss (UHL) and compare them to controls. MATERIALS AND METHODS: We recruited 36 controls, 23 individuals with UHL and 14 with BHL. An HMD (HTC Vive) measured head sway while participants stood on the floor, hips-width apart. Stimuli included two levels of visuals and sound. Root Mean Square Velocity (RMSV) and Power Spectral Density (PSD) were used to quantify head sway. RESULTS: Adjusting for age, individuals with BHL had significantly higher anterior-posterior and medio-lateral RMSV than controls and individuals with UHL. Individuals with UHL demonstrated significantly lower response to visual perturbations in RMSV AP and in all 3 frequency segments of PSD compared to controls. Individuals with UHL showed significantly lower movements at high frequencies compared to controls. Sounds or severity of HL did not impact head sway. CONCLUSIONS: Individuals with BHL demonstrated increased sway with visual perturbations and should be clinically assessed for balance performance and fall risk. Individuals with UHL exhibited reduced responses to visual stimuli compared with controls, which may reflect conscious movement processing. Additional studies are needed to further understand the mechanistic relationship between hearing loss and imbalance.

Quality-Related Process Monitoring and Diagnosis of Hot-Rolled Strip Based on Weighted Statistical Feature KPLS.

Rolling is the main process in steel production. There are some problems in the rolling process, such as insufficient ability of abnormal detection and evaluation, low accuracy of process monitoring, and fault diagnosis. To improve the accuracy of quality-related fault diagnosis, this paper proposes a quality-related process monitoring and diagnosis method for hot-rolled strip based on weighted statistical feature KPLS. Firstly, the process-monitoring and diagnosis model of strip thickness and quality based on the KPLS method is introduced. Then, considering that the KPLS diagnosis method ignores the contribution of process variables to quality, it is easy to misjudge the root cause of quality in the diagnosis process. Based on the rolling mechanism model, the influence weight of strip thickness is constructed. By weighing the statistical data features, a quality diagnosis framework of series structure data fusion is constructed. Finally, the method is applied to the 1580 mm hot-rolling process for industrial verification. The verification results show that the proposed method has higher diagnostic accuracy than PLS, KPLS, and other methods. The results show that the diagnostic model based on weighted statistical feature KPLS has a diagnostic accuracy of more than 96% for strip thickness and quality-related faults.

Morphological Awareness and DHH Students' Reading-Related Abilities: A Meta-Analysis of Correlations.

This article presents the first meta-analysis on correlations of morphological awareness (MA) with reading-related abilities in deaf and hard-of-hearing (DHH) students (k = 14, N = 556). The results showed high mean correlations of MA with all three reading-related abilities: rs = 0.610, 0.712, and 0.669 (all ps < 0.001), respectively, for word reading, vocabulary knowledge, and reading comprehension. A set of moderator analysis was conducted of language, DHH students' age/reading stage and degree of hearing loss, and task type. The correlation of MA with word reading was significantly stronger in alphabetic than in non-alphabetic languages, and for fluency than accuracy; for vocabulary knowledge, the correlation was significantly stronger for production MA tasks than for judgment tasks; for reading comprehension, derivational MA tasks showed a stronger correlation than those having a mixed focus on inflection and derivation. While no other moderator effects were significant, the correlations for subsets of effect sizes were largely high for a moderator. These findings reaffirmed the importance of morphology in DHH students' reading development. The present synthesis, while evidencing major development of research on the metalinguistic underpinnings of reading in DHH students, also showed that the literature on MA is still very limited.

PSC subtyping based on TTF-1 and p40 expression reveals distinct molecular characteristics and therapeutic strategies.

Pulmonary sarcomatoid carcinoma (PSC) is a unique form of poorly differentiated nonsmall cell lung cancer (NSCLC) and is notorious for its highly malignant nature and dismal prognosis. To introduce effective treatment for PSC patients, precise subtyping of PSC is demanding. In our study, TTF-1 and P40 immunohistochemistry (IHC) staining were applied to 56 PSC patients with multiomics data. According to IHC results, we categorized these patients into three subgroups and profiled their molecular contexture using bioinformatic skills. IHC results classified these patients into three subgroups: TTF-1 positive subgroup (n = 27), P40 positive subgroup (n = 15) and double-negative subgroup (n = 14). Spindle cell samples accounted for 35.71% (5/14) of double-negative patients, higher than others (P = .034). The three subgroups were heterogeneous in the genomic alteration spectrum, showing significant differences in the RTK/RAS pathway (P = .004) and the cell cycle pathway (P = .030). The methylation profile of the double-negative subgroup was between the other two subgroups. In similarity analysis, the TTF-1 and p40 subgroups were closely related to LUAD and LUSC, respectively. The TTF-1 positive subgroup had the highest leukocyte fraction (LF) among several cancer types, and the tumor mutation burden (TMB) of the p40 positive subgroup ranked third in the TMB list, suggesting the applicability of immunotherapy for PSC. The study established a new subtyping method of PSC based on IHC results and reveals three subgroups with distinct molecular features, providing evidence for refined stratification in the treatment of PSC.

Extremely sensitive multi-order mode refractive index sensor using TiO2 nanograss film and weakly bounded waveguide modes.

An extremely sensitive multi-order mode refractive index (RI) sensor was fabricated by coupling titanium dioxide nanograss film coated FTO conductive glass with Kretschmann prism. Both calculation and experimental studies were carried out. Theoretical analysis by employing resonant waveguide modes indicated that the maximum sensitivity could be achieved when the mode worked at the weakly-bounded condition. The experimental results showed that for p-polarized and s-polarized light, the sensor exhibited a maximum RI sensitivity of 2938.21 nm/RI unit (RIU) and 1484.39 nm/RIU in the 1st order mode, respectively. Its maximum figure of merit was as high as 77.77. The proposed sensor is promising to be applied in environmental monitoring, immune analysis, nucleic acid test, etc.

Lessons learned from early compassionate use of convalescent plasma on critically ill patients with Covid-19.

BACKGROUND: The management of critically ill patients with coronavirus disease 2019 (COVID-19), caused by a new human virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is challenging. Recently, there have been several reports with inconsistent results after treatment with convalescent plasma (CP) on critically ill patients with COVID-19, which was produced with a neutralizing antibody titer and tested in a P3 or P4 laboratory. However, due to the limitation of the conditions on mass production of plasma, most producers hardly had the capability to isolate the neutralizing antibody. Here, we report the clinical courses of three critically ill patients with COVID-19 receiving CP treatments by total immunoglobulin G (IgG) titer collection. METHODS: Three patients with COVID-19 in this study were laboratory confirmed to be positive for SARS-CoV-2, with radiographic and clinical features of pneumonia. CP was collected by total IgG titer of 160 (range, 200-225 mL), and patients were transfused between 20 and 30 days after disease onset at the critical illness stage as a trial in addition to standard care. The clinical courses of these patients, including laboratory results and pulmonary functional and image studies after receiving convalescent plasma infusions, were reviewed. RESULTS: No therapeutic effect of CP was observed in any of the patients; instead, all three patients deteriorated and required extracorporeal membrane oxygenation treatment. A potential cytokine storm 4 hours after infusion of CP in Patient 2 was observed. No more patients were put on the trial of CP transfusion. CONCLUSIONS: We recommend extreme caution in using CP in critically ill patients more than 2 weeks after the onset of COVID-19 pneumonia.

Serum Cystatin C and Coronavirus Disease 2019: A Potential Inflammatory Biomarker in Predicting Critical Illness and Mortality for Adult Patients.

This study aimed at determining the relationship between baseline cystatin C levels and coronavirus disease 2019 (COVID-19) and investigating the potential prognostic value of serum cystatin C in adult patients with COVID-19. 481 patients with COVID-19 were consecutively included in this study from January 2, 2020, and followed up to April 15, 2020. All clinical and laboratory data of COVID-19 patients with definite outcomes were reviewed. For every measure, COVID-19 patients were grouped into quartiles according to the baseline levels of serum cystatin C. The highest cystatin C level was significantly related to more severe inflammatory conditions, worse organ dysfunction, and worse outcomes among patients with COVID-19 (P values < 0.05). In the adjusted logistic regression analyses, the highest cystatin C level and ln-transformed cystatin C levels were independently associated with the risks of developing critically ill COVID-19 and all-cause death either in overall patients or in patients without chronic kidney disease (P values < 0.05). As a potential inflammatory marker, increasing baseline levels of serum cystatin C might independently predict adverse outcomes for COVID-19 patients. Serum cystatin C could be routinely monitored during hospitalization, which showed clinical importance in prognosticating for adult patients with COVID-19.

MicroRNA-146b correlates with decreased acute respiratory distress syndrome risk, reduced disease severity, and lower 28-day mortality in sepsis patients.

OBJECTIVE: This study aimed to investigate the predictive value of microRNA-146b (miR-146b) on acute respiratory distress syndrome (ARDS) risk, and the correlation of miR-146b with disease severity and 28-day mortality in sepsis patients. METHODS: A total of 104 sepsis patients and 100 healthy controls (HCs) were consecutively enrolled, and miR-146b relative expression in their plasma samples was detected by reverse transcription-quantitative polymerase chain reaction. In sepsis patients, disease severity was assessed using Acute Physiology and Chronic Health Evaluation II (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score. ARDS occurrence and 28-day mortality were recorded. RESULTS: MiR-146b was decreased in sepsis patients compared to HCs. ARDS occurred in 30 (28.8%) sepsis patients, and miR-146b was reduced in ARDS sepsis patients compared to non-ARDS sepsis patients. Meanwhile, miR-146b distinguished ARDS sepsis patients from non-ARDS sepsis patients (area under the curve (AUC): 0.728, 95% confidence interval (CI): 0.627-0.829). Subsequent multivariate logistic regression showed that miR-146b, age, smoke, respiratory infection, and serum creatinine predicted ARDS risk independently, and their combination well-discriminated ARDS sepsis patients from non-ARDS sepsis patients (AUC: 0.863, 95% CI: 0.792-0.934). Additionally, miR-146b was negatively correlated with serum creatinine, white blood cell, C-reactive protein, APACHE II score, and SOFA score, while positively correlated with albumin. Regarding prognosis, miR-146b was decreased in 28-day sepsis deaths compared to 28-day sepsis survivors, and it discriminated 28-day sepsis deaths from 28-day sepsis survivors (AUC: 0.785, 95% CI: 0.680-0.890). CONCLUSION: MiR-146b might serve as a potential biomarker for ARDS prevention and prognostic reflection in sepsis.

Long non-coding RNA CRNDE and toll-like receptor 3 correlate with disease severity, inflammation, and mortality in sepsis.

OBJECTIVE: This study aimed to assess the interaction between long non-coding RNA colorectal neoplasia differentially expressed (lncRNA CRNDE) and toll-like receptor 3 (TLR3), and assess their correlations with disease severity, inflammation, and 28-days mortality in sepsis patients. METHODS: We consecutively enrolled 146 sepsis patients and 146 healthy controls (HCs), and collected their peripheral blood mononuclear cells to detect lncRNA CRNDE and TLR3 expressions using reverse transcription quantitative polymerase chain reaction. LncRNA CRNDE and TLR3 in sepsis patients were classified into four clusters according to quantile expressions (Quantile 1 (0%-24%), Quantile 2 (25%-50%), Quantile 3 (50%-74%), and Quantile 4 (75%-100%)) for correlation analysis. RESULTS: LncRNA CRNDE was upregulated in sepsis patients compared with HCs, and it showed good value in differentiating sepsis patients form HCs by receiver operating characteristic curve analysis. In sepsis patients, lncRNA CRNDE positively correlated with acute pathologic and chronic health evaluation II (APACHE II) score and sequential organ failure assessment (SOFA) score, as well as serum creatinine (Scr). As for inflammation, lncRNA CRNDE positively correlated with C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and IL-8. Regarding mortality, lncRNA CRNDE positively correlated with 28-days mortality. Furthermore, lncRNA CRNDE positively correlated with TLR3, and TLR3 positively associated with APACHE II score, SOFA score, Scr, albumin, CRP, TNF-α, IL-1ß, IL-6, IL-8, and 28-days mortality in sepsis patients. CONCLUSION: LncRNA CRNDE interacts with TLR3, both of which correlate with advanced disease severity, inflammation, and higher 28-days mortality in sepsis patients.

Long noncoding RNA NEAT 1 and its target microRNA-125a in sepsis: Correlation with acute respiratory distress syndrome risk, biochemical indexes, disease severity, and 28-day mortality.

BACKGROUND: Sepsis is one of the main contributors to in-hospital deaths. This study aimed to evaluate the clinical roles of long noncoding RNA (lncRNA) nuclear-enriched abundant transcript 1 (NEAT1) and microRNA (miR)-125a in sepsis. METHODS: LncRNA NEAT1 and miR-125a in plasma samples from 102 sepsis patients and 100 healthy controls (HCs) were detected by reverse transcription-quantitative polymerase chain reaction. In sepsis patients, general disease severity was assessed by acute physiology and chronic health evaluation (APACHE) II score and sequential organ failure assessment (SOFA) score. Meanwhile, acute respiratory distress syndrome (ARDS) occurrence and mortality during 28 days were recorded. RESULTS: LncRNA NEAT1 was increased, but miR-125a was decreased in sepsis patients compared to HCs, and in ARDS sepsis patients compared to non-ARDS sepsis patients. The receiver's operative characteristic (ROC) curves revealed that higher lncRNA NEAT1 or lower miR-125a had certain predictive value for ARDS risk. Further multivariate logistic regression revealed miR-125a but not lncRNA NEAT1 was correlated with ARDS risk independently in sepsis patients. Additionally, lncRNA NEAT1 was positively, but miR-125a was negatively correlated with APACHE II score and SOFA score in sepsis patients. Moreover, higher lncRNA NEAT1 and lower miR-125a were observed in 28-day deaths compared to 28-day survivors and were correlated with increased accumulating mortality in sepsis patients. CONCLUSION: LncRNA NEAT1 high expression and miR-125a low expression correlate with increased ARDS risk, enhanced disease severity, higher 28-day mortality, and negatively associate with each other in sepsis patients.

Interaction of estrogen receptor ß5 and interleukin 6 receptor in the progression of non-small cell lung cancer.

Numerous studies have shown that the estrogen receptor beta (ERß) and interleukin 6 receptor (IL-6R) had interaction in many tumors, including lung cancer. Previous studies found that ERß5 exhibits a different biological function compared with the other subtypes of ERß. Therefore, this study mainly explores the interaction between ERß5 and IL-6R in the progression of lung cancer. We found that the expression of ERß5, IL-6 and glycoprotein 130 (GP130) were significantly increased (P < 0.001) and the 5-year survival rate with the co-expression of ERß5 and GP130 is significantly lower (P = 0.0315) in non-small cell lung cancer (NSCLC) patients. The cell proliferation, invasion, and cell cycle were markedly increased, and the cell apoptotic was markedly inhibited with the concurrent action of ERß5 and IL-6 in A549 cells (P < 0.05). In addition, the expression of ERß5, GP130, p-AKT, and p-44/42 MAPK was also significantly increased in A549 cells (P < 0.05). These results indicate that ERß5 and GP130 can synergistically promote the progression of NSCLC and maybe combined as an independent prognostic factor in patients. In addition, these results also provide a theoretical basis for the combined targeting therapy of ERß5 and GP130 in NSCLC.

Insight into the rheological behaviors of a polyanionic collagen fabricated with poly(γ-glutamic acid)-NHS ester.

The rheological behaviors of a polyanionic collagen, fabricated using poly(γ-glutamic acid)-N-hydroxysuccinimide (γ-PGA-NHS) as a novel modifier, were investigated in this study. It was found that both of the native and modified collagen solutions were pseudoplastic fluids, as shown from the steady-shear tests. While the storage modulus and loss modulus of collagen increased with increasing the amount of γ-PGA-NHS, or with increasing the degree of esterification of γ-PGA-NHS; meanwhile, the dynamic denaturation temperature determined by dynamic temperature sweep was also increased, indicating an improved thermal stability of collagen solution modified by γ-PGA-NHS. The creep-recovery measurements showed that the resistance to deformation was enhanced for modified collagen, probably due to the cross-linking occurred between the ε-amino groups of collagen molecules and α-COOH groups of γ-PGA-NHS, as well as the electrostatic interaction and hydrogen-bond interactions between the two molecules. Furthermore, the aggregation of collagen fibers was promoted due to these interactions between collagen and γ-PGA-NHS as observed by atomic force morphology. In addition, the modified collagen exhibited good cytocompatibility as demonstrated by cell growth culturing. The obtained information was expected to give valuable clues to the design and fabrication of controlled stable collagen-based products for applications in various biomedical fields.

PGAP-X: extension on pan-genome analysis pipeline.

BACKGROUND: Since PGAP (pan-genome analysis pipeline) was published in 2012, it has been widely employed in bacterial genomics research. Though PGAP has integrated several modules for pan-genomics analysis, how to properly and effectively interpret and visualize the results data is still a challenge. RESULT: To well present bacterial genomic characteristics, a novel cross-platform software was developed, named PGAP-X. Four kinds of data analysis modules were developed and integrated: whole genome sequences alignment, orthologous genes clustering, pan-genome profile analysis, and genetic variants analysis. The results from these analyses can be directly visualized in PGAP-X. The modules for data visualization in PGAP-X include: comparison of genome structure, gene distribution by conservation, pan-genome profile curve and variation on genic and genomic region. Meanwhile, result data produced by other programs with similar function can be imported to be further analyzed and visualized in PGAP-X. To test the performance of PGAP-X, we comprehensively analyzed 14 Streptococcus pneumonia strains and 14 Chlamydia trachomatis. The results show that, S. pneumonia strains have higher diversity on genome structure and gene contents than C. trachomatis strains. In addition, S. pneumonia strains might have suffered many evolutionary events, such genomic rearrangements, frequent horizontal gene transfer, homologous recombination, and other evolutionary process. CONCLUSION: Briefly, PGAP-X directly presents the characteristics of bacterial genomic diversity with different visualization methods, which could help us to intuitively understand dynamics and evolution in bacterial genomes. The source code and the pre-complied executable programs are freely available from http://pgapx.ybzhao.com .

The Differentially Expressed Circular RNAs in the Substantia Nigra and Corpus Striatum of Nrf2-Knockout Mice.

BACKGROUND/AIMS: The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a protective role in both acute neuronal damage and chronic neurodegeneration-related oxidative stress. Circular RNAs (circRNAs) are involved with various diseases in the central nervous system (CNS). This study aimed to identify the key circRNAs involved in Nrf2-neuroprotection against oxidative stress. METHODS: The differentially expressed circRNAs (DEcircRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice were identified by microarray analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of selected DEcircRNAs in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice. Based on our previous microarray analysis of the differentially expressed mRNAs (DEmRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice, the DEcircRNA-miRNA-DEmRNA interaction network was constructed. Functional annotation of DEmRNAs that shared the same binding miRNAs with DEcircRNAs was performed using gene ontology (GO) and pathway analyses. RESULTS: A total of 65 and 150 significant DEcircRNAs were obtained in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, respectively, and seventeen shared DEcircRNAs were found in both these two tissues. The qRT-PCR results were generally consistent with the microarray results. The DEcircRNA-miRNA-DEmRNA interaction network and pathway analysis indicated that mmu_circRNA_34132, mmu_circRNA_017077 and mmu-circRNA-015216 might be involved with Nrf2-mediated neuroprotection against oxidative stress. Mmu_circRNA_015216 and mmu_circRNA_017077 might play roles in the Nrf2-related transcriptional misregulation and Nrf2-mediated processes of rheumatoid arthritis, respectively. In addition to these two processes, mmu_circRNA_34132 may be a potential regulator of Nrf2-mediated protection for diabetes mellitus and Nrf2-mediated defence against ROS in hearts. CONCLUSION: In conclusion, our study identified the key DEcircRNAs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, which might provide new clues for further exploring the mechanism of Nrf2-mediated neuroprotection against oxidative stress and other Nrf2-mediated processes.

Effect of piperine on the bioavailability and pharmacokinetics of rosmarinic acid in rat plasma using UPLC-MS/MS.

1. The purpose of the present study was to investigate the effect of piperine (PP) on the pharmacokinetics of rosmarinic acid (RA) in rat plasma and to determine whether PP could enhance the oral bioavailability of RA via inhibition of its glucuronidation. 2. The pharmacokinetic profiles of RA between oral administration of RA (50 mg/kg) alone and in combination with different oral dose PP (20, 40, 60, and 80 mg/kg) to rats were investigated via a validated UPLC/MS/MS method. 3. The AUC and Cmax of RA were significantly increased in combination with different dose PP dose dependently, especially in the presence of 60 and 80 mg/kg PP (p < 0.01). The relative bioavailability of RA in the presence of 20, 40, 60, and 80 mg/kg PP was 1.24-, 1.32-, 2.02-, and 2.26-folds higher, respectively, compared with the control group given RA alone. Compared with RA, the pharmacokinetic modulations of RA glucuronide were even more apparent, and the glucuronidation of RA was remarkedly inhibited. 4. This study demonstrated that PP significantly improved the in vivo bioavailability of RA partly attributing to the inhibition of gut and hepatic metabolism enzymes of RA.

An Ultrasensitive Long-Period Fiber Grating-Based Refractive Index Sensor with Long Wavelengths.

The response of a novel long-period fiber grating (LPFG) with a period of 180 µm to a surrounding refractive index (RI) was investigated. The results displayed that, with the increase in RI of the surrounding media of cladding glass in the grating region, the resonant peak located at 1336.4 nm in the transmission spectrum gradually shifts towards a shorter wavelength, while the resonant peak located at 1618 nm gradually shifted towards a longer wavelength. Moreover, the resonant peak at 1618 nm is much more sensitive to the surrounding RI than that of the one at 1336.4 nm. Compared with the conventional LPFG and other types of wavelength-interrogated RI sensors, such as ring resonators, surface plasmon resonance sensors, and Fabry-Perot interferometric sensors, this novel LPFG possesses a higher sensitivity, which achieved 10,792.45 nm/RIU (RI unit) over a RI range of 1.4436-1.4489.