Machine learning based on biological context facilitates the identification of microvascular invasion in intrahepatic cholangiocarcinoma.

Intrahepatic cholangiocarcinoma is a rare disease associated with a poor prognosis, primarily due to early recurrence and metastasis. An important feature of this condition is microvascular invasion (MVI). However, current predictive models based on imaging have limited efficacy in this regard. This study employed a random forest model to construct a predictive model for MVI identification and uncover its biological basis. Single-cell transcriptome sequencing, whole exome sequencing, and proteome sequencing were performed. The area under the curve of the prediction model in the validation set was 0.93. Further analysis indicated that MVI-associated tumor cells exhibited functional changes related to epithelial-mesenchymal transition and lipid metabolism due to alterations in the nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways. Tumor cells were also differentially enriched for the interleukin-17 signaling pathway. There was less infiltration of SLC30A1+ CD8+ T cells expressing cytotoxic genes in MVI-associated intrahepatic cholangiocarcinoma, whereas there was more infiltration of myeloid cells with attenuated expression of the major histocompatibility complex II pathway. Additionally, MVI-associated intercellular communication was closely related to the SPP1-CD44 and ANXA1-FPR1 pathways. These findings resulted in a brilliant predictive model and fresh insights into MVI.

Artificial intelligence improves microvascular invasion (MVI) recognition. Multi-omics studies reveal malignant features associated with MVI. Tumors with MVI have disrupted lipid metabolism. MVI indicates a suppressive immune microenvironment. MVI can serve as a foundation for immunotherapy selection.

Differential isocitrate dehydrogenase 1 and isocitrate dehydrogenase 2 mutation-related landscape in intrahepatic cholangiocarcinoma.

BACKGROUND: Patients with intrahepatic cholangiocarcinoma (ICC) are prone to recurrence and poor survival. Targeted therapy related to isocitrate dehydrogenase (IDH) is an extremely important treatment. IDH1 and IDH2 mutations are generally thought to have similar effects on the tumor landscape. However, it is doubtful whether these 2 mutations have exactly the same effects on tumor cells and the tumor microenvironment. METHODS: All collected tumor samples were subjected to simultaneous whole-exon sequencing and proteome sequencing. RESULTS: IDH1 mutations accounted for 12.2%, and IDH2 mutations accounted for 5.5%, all missense mutations. Tumors with IDH mutations had lower proportions of KRAS and TP53 mutations. Mutated genes were obviously enriched in the kinase pathway in the tumors with IDH2 mutations. The signaling pathways were mainly enriched in the activation of cellular metabolic activities and an increase of inhibitory immune cells in the tumors with IDH mutations. Moreover, tumors had unique enrichment in DNA repair in IDH1 mutants and secretion of biological molecules in IDH2 mutants. Inhibitory immune cells might be more prominent in IDH2 mutants, and the expression of immune checkpoints PVR and HLA-DQB1 was more prominent in IDH1 mutants. IDH mutants were more related to metabolism-related and inflammation-immune response clusters, and some belonged to the DNA replication and repair cluster. CONCLUSIONS: These results revealed the differential IDH1 and IDH2 mutation-related landscapes, and we have provided an important reference database to guide ICC treatment.

EMLI-ICC: an ensemble machine learning-based integration algorithm for metastasis prediction and risk stratification in intrahepatic cholangiocarcinoma.

Robust strategies to identify patients at high risk for tumor metastasis, such as those frequently observed in intrahepatic cholangiocarcinoma (ICC), remain limited. While gene/protein expression profiling holds great potential as an approach to cancer diagnosis and prognosis, previously developed protocols using multiple diagnostic signatures for expression-based metastasis prediction have not been widely applied successfully because batch effects and different data types greatly decreased the predictive performance of gene/protein expression profile-based signatures in interlaboratory and data type dependent validation. To address this problem and assist in more precise diagnosis, we performed a genome-wide integrative proteome and transcriptome analysis and developed an ensemble machine learning-based integration algorithm for metastasis prediction (EMLI-Metastasis) and risk stratification (EMLI-Prognosis) in ICC. Based on massive proteome (216) and transcriptome (244) data sets, 132 feature (biomarker) genes were selected and used to train the EMLI-Metastasis algorithm. To accurately detect the metastasis of ICC patients, we developed a weighted ensemble machine learning method based on k-Top Scoring Pairs (k-TSP) method. This approach generates a metastasis classifier for each bootstrap aggregating training data set. Ten binary expression rank-based classifiers were generated for detection of metastasis separately. To further improve the accuracy of the method, the 10 binary metastasis classifiers were combined by weighted voting based on the score from the prediction results of each classifier. The prediction accuracy of the EMLI-Metastasis algorithm achieved 97.1% and 85.0% in proteome and transcriptome datasets, respectively. Among the 132 feature genes, 21 gene-pair signatures were developed to establish a metastasis-related prognosis risk-stratification model in ICC (EMLI-Prognosis). Based on EMLI-Prognosis algorithm, patients in the high-risk group had significantly dismal overall survival relative to the low-risk group in the clinical cohort (P-value < 0.05). Taken together, the EMLI-ICC algorithm provides a powerful and robust means for accurate metastasis prediction and risk stratification across proteome and transcriptome data types that is superior to currently used clinicopathological features in patients with ICC. Our developed algorithm could have profound implications not just in improved clinical care in cancer metastasis risk prediction, but also more broadly in machine-learning-based multi-cohort diagnosis method development. To make the EMLI-ICC algorithm easily accessible for clinical application, we established a web-based server for metastasis risk prediction (http://ibi.zju.edu.cn/EMLI/).

Modulation of the tumour microenvironment in hepatocellular carcinoma by tyrosine kinase inhibitors: from modulation to combination therapy targeting the microenvironment.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Tyrosine kinase inhibitors (TKIs) remain the backbone of systematic therapy for advanced hepatocellular carcinoma. Sorafenib and lenvatinib are currently approved as first-line therapeutic drugs, and regorafenib and cabozantinib are applied as second-line treatments. With inhibition of angiogenesis as the main target, TKIs exert a profound effect on the tumour microenvironment (TME). The TME is a complex mixture of cellular and noncellular components surrounding the tumour mass, and is associated with tumour progression partially through the epithelial-mesenchymal transition. Specifically, the TME of HCC is characterized by profound extracellular matrix remodelling and an immunosuppressive microenvironment. The purpose of this review is to provide a summary of TME remodelling mediated by four Food and Drug Administration approved TKIs in HCC and thus summarize the rationale and potential targets for combination therapy. The modulatory effect of TKIs on the TME of HCC was reported to enhance the antitumour effect of TKIs through pyroptosis of macrophages and subsequent natural killer cell activation, T cell activation, regulatory T cell reduction in HCC. Meanwhile, TKIs also induce drug resistance via M2 polarization and accumulation, recruitment of tumour-associated neutrophils, and induction of the epithelial-mesenchymal transition. In conclusion, the effect of TKIs on TME can enhance its antitumour effect, but might also partially contribute to the drug resistance that hinders the progression of TKIs as treatment for HCC. Additionally, the effect of TKIs also provides the rationale for combination therapy, including combining TKIs with immune checkpoint inhibitors, to facilitate increased drug efficacy of TKIs.

Directed transport of symmetrically periodic system induced by "color" breaking of noise.

In general, no transport can emerge in a spatially symmetric periodic system subjected to an unbiased dichotomous periodic driving. Here, we used a noise, which switches synchronously with the driving in three cases [switch between Gaussian white noise and colored noise, two colored noises with different colors (e.g., autocorrelation rate), and Gaussian white noise and harmonic velocity noise], to drive such a symmetric system. Numerical results for the cases indicate that the directed transport of the symmetric system can be induced merely by the color breaking (the difference in two autocorrelation rates) of the switch noise. The amplitude of current depends on the difference, i.e., the greater the difference, the greater the current. Also, the greater autocorrelation rate between the two noises determines the direction of current. The current as a function of the noise intensity for all cases has in common that appropriate noise intensity induces optimal transport. Further investigations show that the color breaking comes from the difference of barrier heights between the left and right-tilted potentials induced by the different autocorrelation rates.

Symmetry breaking: Abnormal transport induced by mass modulation.

Here, we investigate transport of an inertial particle in a symmetric periodic potential and subjected to an external signal, such that mass of the particle is modulated sinusoidally. Our numerical results indicate that the mass modulation can induce abnormal transport in the system, whereas no current appears in the case of constant mass. In the absence of external bias, direction of mean velocity of the particle changes several times as amplitude and frequency of the mass modulation are varied, i.e., a multiple current reversals (CR) phenomenon. The multiple CRs result from temporal symmetry breaking of the system. In the presence of external bias, multiple absolute negative mobilities (ANM) take place in the system. Intrinsic physical mechanisms responsible for the occurrence of the multiple ANMs are analyzed in detail.

Effects of fermentation on antioxidant properties and phytochemical composition of soy germ.

BACKGROUND: Traditional soy-fermented foods, such as miso, douche, natto, and tempeh have been widely used as a dietary supplement in Asian countries, and numerous reports on their phenolics and antioxidant activities have been published. Soy germ contains 10-fold higher phenolics than whole soybean, hence using soy germ as fermentation substrate will be more efficient than whole soybean. RESULTS: Soy germ fermented with Aspergillus niger M46 resulted in a high-efficiency bio-transformation of phenolics and flavonoids to their metabolites, and a diverse secondary metabolic product was also found to response oxidation stress of fungal colonisation. Its antioxidant activity against hydroxyl radicals and superoxide radicals (IC50 = 0.8 and 6.15 µg mL(-1) , respectively) was about 205-fold and 47-fold higher than those of unfermented soy germ (IC50 = 164.0 and 290.48 µg mL(-1) ), respectively. These results were similar to those observed for Trolox, and more active than those of BHT and hesperidin. The ß-glucosidase and α-amylase produced during fermentation were mainly responsible for mobilisation of the phenolics. CONCLUSION: Our results demonstrate that fermented soy germ has the potential to be a good dietary supplement for prevention of oxidative stress-related diseases, and the solid-state bioprocessing strategy could be an innovative approach to enhance the antioxidant activity of soy germ.

Effects of Monocular Flicker on Binocular Imbalance in Amblyopic and Nonamblyopic Adults.

Purpose: This study aimed to evaluate the effects of monocular flicker stimulation on binocular imbalance in both amblyopic and nonamblyopic adults. Methods: Seven amblyopic patients (28.3 ± 3.3 years; four females) and seven normally sighted participants (27.3 ± 4.1 years; five females) participated in the study. We used liquid crystal spectacles to create externally-generated monocular flicker (4, 7, 10, 15, or 20 Hz) and used the metric of log balance point (logBP) to determine whether imposed flicker could change the eyes' equilibrium interocular contrast ratio. Flicker was applied to either the fellow eye vs. the amblyopic eye or dominant eye (DE) vs. non-DE (non-DE) of amblyopic and nonamblyopic participants, respectively. We defined a logBP of 0 to indicate complete binocular balance and an increase in logBP relative to baseline to indicate a relative strengthening of the non-DE or amblyopic eye. Results: Monocular flicker applied to the DE or fellow eye increased logBP, whereas when applied to the non-DE or amblyopic eye, reduced the logBP. These effects were more pronounced at low temporal frequencies than that at high temporal frequencies. The interaction between eye and temporal frequency was significant in both normals, F(4, 24) = 58.082, P < 0.001, η2 = 0.906, and amblyopes, F(1.923, 11.538) = 60.555, P < 0.001, η2 = 0.91. Conclusions: Monocular flicker diminishes the contribution of the flickered eye in binocular combination, resulting in a relative dominance of the nonflickered eye in interocular interactions. Furthermore, a more pronounced temporally modulated effect was observed at lower temporal frequencies.

Rapid Alternate Flicker Modulates Binocular Interaction in Adults With Abnormal Binocular Vision.

Purpose: The current understanding of binocular processing is primarily derived from static spatial visual perception: this leaves the role of temporal information unclear. In this study, we addressed this gap by testing the effect of alternating flicker on binocular information processing in adults with abnormal binocular vision. Our goal was to determine which temporal frequency optimally balanced input from both eyes. Methods: We took measurements in four groups of human adults: 10 normal adults with the individual's nondominant eye covered by a 2% neutral density filter (aged 25.60 ± 1.43 years, experiment 1), 9 nonamblyopic anisometropes (aged 24.33 ± 1.66 years, experiment 2), 7 amblyopes (aged 26.5 ± 1.64 years, experiment 3), and 7 treated amblyopes (aged 24 ± 3.21 years, experiment 4). The balance point (BP), where participants' two eyes are equally effective, was measured using a binocular orientation combination task at four spatial frequencies (SFs; 0.5-4 c/d) and five temporal frequencies (TFs; baseline and 4, 7, 10, and 15 Hz). Its log transformation |logBP| was taken into further analysis. Results: We observed clear U-shaped temporal tuning of the |logBP| for the entire range of TFs (that we measured: trough occurred at 7 Hz). This pattern occurred and was significant in all four groups (P < 0.001). In addition, the effect of SFs on |logBP| was significant in normal, amblyopic, and treated amblyopic groups (all P < 0.001) and was marginally significant in the nonamblyopic anisometropic group (P = 0.086). Conclusions: Alternating flicker around 7 Hz may be the optimal temporal frequency for balancing eyes in human adults with binocular imbalance.

Biocompatible Snowman-like Dimer Nanoparticles for Improved Cellular Uptake in Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma (ICC) is one of the most aggressive types of human cancers. Although paclitaxel (PTX) was proven to exert potent anti-tumor effects against ICC, the delivery of PTX is still challenging due to its hydrophobic property. Nanoparticle (NP)-based carriers have been proven to be effective drug delivery vehicles. Among their physicochemical properties, the shape of NPs plays a crucial role in their performance of cellular internalization and thus anti-tumor efficacy of loaded drugs. In this study, dumbbell-like and snowman-like dimer NPs, composed of a polylactic acid (PLA) bulb and a shellac bulb, were designed and prepared as drug nanocarriers to enhance the efficiency of cellular uptake and anti-tumor performance. PLA/shellac dimer NPs prepared through rapid solvent exchange and controlled co-precipitation are biocompatible and their shape could flexibly be tuned by adjusting the concentration ratio of shellac to PLA. Drug-loaded snowman-like PLA/shellac dimer NPs with a sharp shape exhibit the highest cellular uptake and best cell-killing ability against cancer cells in an in vitro ICC model over traditional spherical NPs and dumbbell-like dimer NPs, as proven with the measurements of flow cytometry, fluorescent confocal microscopy, and the CCK8 assay. The underlying mechanism may be attributed to the lower surface energy required for the smaller bulbs of snowman-like PLA/shellac dimer NPs to make the initial contact with the cell membrane, which facilitates the subsequent penetration through the cellular membrane. Therefore, these dimer NPs provide a versatile platform to tune the shape of NPs and develop innovative drug nanocarriers that hold great promise to enhance cellular uptake and therapeutic efficacy.

Decomposing the Response Time in Amblyopia: A Drift Diffusion Model Analysis.

Purpose: Amblyopes are known to have delayed response times (RT) in various visual tasks. We aim to investigate whether any factor other than the sensory deficit contributes to the delayed RT in amblyopia. Method: Fifteen amblyopic (26.0 ± 4.50 years) and 15 normal (25.6 ± 2.90 years) participants took part in this study. The responses and RTs in an orientation identification task were collected for each participant with stimulus contrast adjusted to the multiples of individual's threshold. A drift diffusion model was used to fit to the response and RT data and to estimate the RT components. Result: There was a significant difference in the RT between the amblyopic and normal groups (F(1, 28) = 6.75, P = 0.015) but no difference in the accuracy (F(1, 28) = 0.028, P = 0.868). The drift rate function in the amblyopic eye had a larger threshold (P = 0.001) and shallower slope (P = 0.006) than that of the fellow eye. The amblyopic group has a longer non-decision time than the normal group (F(1, 28) = 8.02, P = 0.008). The drift rate threshold correlated with the contrast sensitivity (P = 1.71 × 10-18) but the non-decision time did not (P = 0.393). Conclusions: Both sensory and post-sensory factors contributed to the delayed RT in amblyopia. The effect of the sensory loss in V1 on RT can be compensated by increasing stimulus contrast, and the post-sensory delay provides evidence for higher-level deficits in amblyopia.

Proteomic and single-cell landscape reveals novel pathogenic mechanisms of HBV-infected intrahepatic cholangiocarcinoma.

Despite the epidemiological association between intrahepatic cholangiocarcinoma (ICC) and hepatitis B virus (HBV) infection, little is known about the relevant oncogenic effects. A cohort of 32 HBV-infected ICC and 89 non-HBV-ICC patients were characterized using whole-exome sequencing, proteomic analysis, and single-cell RNA sequencing. Proteomic analysis revealed decreased cell-cell junction levels in HBV-ICC patients. The cell-cell junction level had an inverse relationship with the epithelial-mesenchymal transition (EMT) program in ICC patients. Analysis of the immune landscape found that more CD8 T cells and Th2 cells were present in HBV-ICC patients. Single-cell analysis indicated that transforming growth factor beta signaling-related EMT program changes increased in tumor cells of HBV-ICC patients. Moreover, ICAM1+ tumor-associated macrophages are correlated with a poor prognosis and contributed to the EMT in HBV-ICC patients. Our findings provide new insights into the behavior of HBV-infected ICC driven by various pathogenic mechanisms involving decreased cell junction levels and increased progression of the EMT program.

The Landscape and Clinical Application of the Tumor Microenvironment in Gastroenteropancreatic Neuroendocrine Neoplasms.

Gastroenteropancreatic neuroendocrine neoplasms feature high heterogeneity. Neuroendocrine tumor cells are closely associated with the tumor microenvironment. Tumor-infiltrating immune cells are mutually educated by each other and by tumor cells. Immune cells have dual protumorigenic and antitumorigenic effects. The immune environment is conducive to the invasion and metastasis of the tumor; in turn, tumor cells can change the immune environment. These cells also form cytokines, immune checkpoint systems, and tertiary lymphoid structures to participate in the process of mutual adaptation. Additionally, the fibroblasts, vascular structure, and microbiota exhibit interactions with tumor cells. From bench to bedside, clinical practice related to the tumor microenvironment is also regarded as promising. Targeting immune components and angiogenic regulatory molecules has been shown to be effective. The clinical efficacy of immune checkpoint inhibitors, adoptive cell therapy, and oncolytic viruses remains to be further discussed in clinical trials. Moreover, combination therapy is feasible for advanced high-grade tumors. The regulation of the tumor microenvironment based on multiple omics results can suggest innovative therapeutic strategies to prevent tumors from succeeding in immune escape and to support antitumoral effects.

Cancer cell membrane-wrapped nanoparticles for cancer immunotherapy: A review of current developments.

Background: As the forefront of nanomedicine, bionic nanotechnology has been widely used for drug delivery in order to obtain better efficacy but less toxicity for cancer treatments. With the rise of immunotherapy, the combination of nanotechnology and immunotherapy will play a greater potential of anti-tumor therapy. Due to its advantage of homologous targeting and antigen library from source cells, cancer cell membrane (CCM)-wrapped nanoparticles (CCNPs) has become an emerging topic in the field of immunotherapy. Key scientific concepts of review: CCNP strategies include targeting or modulating the tumor immune microenvironment and combination therapy with immune checkpoint inhibitors and cancer vaccines. This review summarizes the current developments in CCNPs for cancer immunotherapy and provides insight into the challenges of transferring this technology from the laboratory to the clinic as well as the potential future of this technology. Conclusion: This review described CCNPs have enormous potential in cancer immunotherapy, but there are still challenges in terms of translating their effects in vitro to the clinical setting. We believe that these challenges can be addressed in the future with a focus on individualized treatment with CCNPs as well as CCNPs combined with other effective treatments.

Immunotherapy of cholangiocarcinoma: Therapeutic strategies and predictive biomarkers.

Cholangiocarcinoma (CCA) is a group of malignant heterogeneous cancer arising from the biliary tree. CCA has become a global health problem with rising incidence and mortality that threatens the health of human beings. The immune microenvironment of CCA is characterized by abundant cancer-associated fibroblast and suppressive immune components. The increasing body of knowledge and recent developments in transcriptomic studies have given insight into the immune landscape of CCA, paving the way for better application of immunotherapy. Immunotherapy mainly applies in a limited subset of CCA with deficient mismatch and high microsatellite instability. With limited response rates and treatment efficacy, researchers are looking into novel strategies on combination strategies and alternatives, such as immune vaccines and adoptive cell therapy. Biomarker identification is also critical for patient selection. We present an up-to-date summary of the current research on immunotherapy for CCA patients, covering pre-clinical and clinical exploration beyond immune checkpoint inhibitors, immune vaccines, and adoptive cell therapy. In addition, we review the promising biomarkers for CCA immunotherapy and discuss recent development.

Quiquelignan A-H, eight new lignoids from the rattan palm Calamus quiquesetinervius and their antiradical, anti-inflammatory and antiplatelet aggregation activities.

Eight new lignin derivatives, termed quiquelignan A-H (1-8), comprising three tricin-type flavonolignans (1-3) and five 8-O-4' neolignans (4-8), were isolated from the ethanol extract of Calamus quiquesetinervius stems. Structural elucidation of the new isolates was accomplished on the basis of spectroscopic data. Compounds 1-8 showed strong-to-moderate antioxidant activity against the hydroxy radical (()OH). Among them, compound 5 showed significantly higher hydroxy radical scavenging activity (IC(50) 4.4microg/mL). Compounds 2-4 and 6-8 dose-dependently suppressed the LPS-stimulated production of nitric oxide (NO) in RAW 264.7 cells. The anti-inflammatory potency of 4 and 6 was 2.7-4.5-fold higher compared with quercetin. Compounds 2-4, 6 and 8 also exhibited mild collagen-antagonistic activity, but were inactive with respect to thrombin-induced platelet aggregation.

Adverse birth outcomes in Guangdong province, China, 2014-2017: a spatiotemporal analysis of 2.9 million births.

OBJECTIVES: Adverse birth outcomes pose a great threat to the public health and bring a heavy burden of disease in China. A comprehensive examination of the temporal and spatial trends of preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) epidemics can provide some elementary information for subsequent aetiological and epidemiological studies. This study aimed to characterise the spatiotemporal features of PTB, LBW and SGA based on a large cohort of live births in China. DESIGN: Spatiotemporal descriptive analysis was performed in Guangdong province, China, from 2014 to 2017. SETTING: Data involving 2 917 098 live births in Guangdong province, China from 2014 to 2017 was collected from Guangdong Birth Certificate System. Information was collected, including the date of birth, gestational age in week, birth weight, sex of the infant, age of the mother and registered residence of the mother. RESULTS: The estimated rate of PTB, LBW and SGA was 4.16%, 4.14% and 12.86%, respectively. For temporal trends, the rates of PTB, LBW and SGA showed seasonal fluctuations, especially for LBW and SGA. In addition, there were regional differences in the rates of PTB, LBW and SGA between the Pearl River Delta and Non-Pearl River Delta regions. From 2014 to 2017, the high rates of PTB and LBW expanded from the Pearl River Delta region to the Non-Pearl River Delta regions. However, compared with the Pearl River Delta region, the rate of SGA was higher in the Non-Pearl River Delta regions on the whole. CONCLUSION: The findings of this study contribute to the understanding of the aetiology and epidemiology of PTB, LBW and SGA in south China.

High prevalence of hyperuricaemia and its impact on non-valvular atrial fibrillation: the cross-sectional Guangzhou (China) Heart Study.

OBJECTIVES: There are country and regional variations in the prevalence of hyperuricaemia (HUA). The prevalence of HUA and non-valvular atrial fibrillation (NVAF) in southern China is unknown. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: A total of 11 488 permanent residents aged 35 or older from urban and rural areas of Guangzhou, China were enrolled. A questionnaire was used to compile each participant's demographic information and relevant epidemiological factors for HUA and NVAF. All participants were assessed using a panel of blood tests and single-lead 24-hour ECG. MAIN OUTCOME MEASURES: HUA was defined as serum uric acid level >420 µmol/L in men and >360 µmol/L in women. NVAF was diagnosed as per guidelines. RESULTS: The prevalence of HUA was 39.6% (44.8% in men and 36.7% in women), and 144 residents (1.25%) had NVAF. Prevalence of HUA increased with age in women but remained stably high in men. After adjusting for potential confounders, age, living in urban areas, alcohol consumption, central obesity, elevated fasting plasma glucose level, elevated blood pressure, lower high-density lipoprotein cholesterol level and elevated triglycerides level were associated with increased risk of HUA. Residents with HUA were at higher risk for NVAF. Serum uric acid level had a modest predictive value for NVAF in women but not men. CONCLUSIONS: HUA was highly prevalent among citizens of southern China and was a predictor of NVAF among women.

Curcuminoid submicron particle ameliorates cognitive deficits and decreases amyloid pathology in Alzheimer's disease mouse model.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder and is triggered via abnormal accumulation of amyloid-ß peptide (Aß). Aggregated Aß is responsible for disrupting calcium homeostasis, inducing neuroinflammation, and promoting neurodegeneration. In this study, we generated curcuminoid submicron particle (CSP), which reduce the average size to ~60 nm in diameter. CSP had elevated the bioavailability in vivo and better neuroprotective effect against oligomeric Aß than un-nanosized curcuminoids in vitro. Two months of CSP consumption reversed spatial memory deficits and the loss of a calcium binding protein calbindin-D28k in the hippocampus of AD mouse model. In addition, CSP consumption lowered amyloid plaques and astrogliosis in vivo and enhanced microglial Aß phagocytosis in vitro, implying that the beneficial effects of CSP also mediated via modulating neuroinflammation and enhancing amyloid clearance. Taken together, our study demonstrated the protective effects of CSP toward ameliorating the memory impairment and pathological deficits in AD mouse model.

Purification and properties of a novel phenolic antioxidant from Radix astragali fermented by Aspergillus oryzae M29.

The Chinese herb Radix astragalus (RA) has been widely used as a dietary supplement in Asia, and there are numerous reports on its bioactivities. However, there are no reports to date regarding the use of Aspergillus spp. in the culture medium of the RA plant for the production of phenolic antioxidants. In this study, utilizing the fungus Aspergillus to ferment the native RA has successfully resulted in a significant increase in the phenolic contents of RA, and the fermented RA also revealed much better antioxidant activity toward 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals, hydroxyl radical, superoxide radical and peroxyl radical than those of unfermented RA. Among these phenolics, a potent novel antioxidant was isolated and identified as 3,4-di(4'-hydroxyphenyl) isobutyric acid with a molecular weight of 272, by ESI-MS (electrospray ionization mass), ¹H NMR (nuclear magnetic resonance), ¹³C NMR, DEPT (distortionless enhancement by polarization transfer)-NMR, HMQC (heteronuclear multiple quantum coherence), and HMBC (heteronuclear multiple bond correlation) spectra. These data demonstrated that the solid-state bioprocessing strategy could be an innovative approach to enhance the antioxidant activity of RA.