Mismatch of MRI White Matter Hyperintensities and Gait Function in Patients With Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease (CSVD) is closely related to gait disorders. Previous studies have found a negative correlation between the severity of MRI white matter hyperintensities (WMH) and gait speed. However, not every individual with WMH experiences a gait disorder. PURPOSE: To investigate the mechanisms underlying the mismatch between the severity of MRI WMH and gait impairment, in particular in subjects with severe WMH (Fazekas 3, scale 0-3) resulting from vascular disease. STUDY TYPE: Cohort. POPULATION: 54 subjects with severe WMH and gait disorder (WMH-GD; 29 males) and 114 subjects with severe WMH with no gait disorder (WMH-nGD; 60 males). FIELD STRENGTH/SEQUENCE: 3T/diffusion tensor imaging (DTI), and T1-weighted, T2-weighted, FLAIR, DWI, SWI. ASSESSMENT: Trace-based spatial statistics analysis (TBSS) approach (fractional anisotropy, FA; mean diffusivity; radial diffusivity; axial diffusivity); Cognitive assessment; Conventional MRI markers of CSVD (WMH, enlarged perivascular spaces, lacunae, and cerebral microbleeds); Gait parameters (gait speed; cadence; stride length; gait cycle duration; step duration; time-up-and-go test, TUG). Gait disorder was defined as a TUG time exceeding 12 sec. STATISTICAL TESTS: The t-tests, Mann-Whitney U tests, Chi-square tests, and partial correlation analysis (Pearson or Spearman) were used. P < 0.05 with threshold-free cluster enhancement corrected was considered statistically significant for TBSS. RESULTS: After adjusting for age, sex, height, and other conventional MRI markers of CSVD, the WMH-nGD group showed significantly decreased FA values in the corpus callosum, bilateral superior longitudinal fasciculus, left corona radiata, and left posterior thalamic radiation. There was a significant association between FA values and TUG time, gait speed, and stride length in multiple WM tracts, independent of other conventional CSVD markers. DATA CONCLUSION: This study provides evidence for microstructural damage of specific fibers in WMH-GD subjects compared to WMH-nGD subjects. This may explain the mismatch between WMH and gait impairment in subjects with severe WMH. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 3.

Certification of visinin-like protein-1 (VILIP-1) certified reference material by amino acid-based and sulfur-based liquid chromatography isotope dilution mass spectrometry.

As an emerging neurodegenerative disease, Alzheimer's disease (AD) has become a leading cause of dementia in older adults. Visinin-like protein-1 (VILIP-1) is an increasingly used biomarker for AD besides the widely accepted Aß1-40, Aß1-42, and tau. However, significant variations exist in the commercial immuno-based assays for VILIP-1 quantification, underlining the necessity to establish a traceability chain. Certified reference materials (CRMs) located at the top of the traceability chain are traceability sources for relevant matrix standard materials. In this work, VILIP-1 solution CRM with a certified value and uncertainty of 39.82±1.52 µg·g-1 was developed and certified using amino acid-based isotope dilution mass spectrometry (AA-ID-MS) and sulfur-based isotope dilution inductively coupled plasma mass spectrometry (ID-ICP-MS). Certified values from both strategies showed great consistency, with traceability to SI units. Moreover, the candidate VILIP-1 CRM shows excellent homogeneity and can be stable for at least 7 days at -20°C and 12 months at -70°C. The VILIP-1 CRM developed can be used in value assignment to secondary calibrators and clinical matrix CRMs, showing prospects in early diagnosis and disease monitoring for AD.

Absolute Quantification of Total Hemoglobin in Whole Blood by High-Performance Liquid Chromatography Isotope Dilution Inductively Coupled Plasma-Mass Spectrometry.

Accurate and traceable measurement of hemoglobin (HGB) is of great importance in clinical testing. Although the HiCN method is the internationally accepted conventional reference method for this biomarker and frequently used in clinical routine diagnostics, the HiCN method cannot be traceable to the International System of Units (SI) and thus does not meet highest metrological demands. In this study, an absolute quantitative approach for total HGB in a whole blood sample is proposed based on the determination of natural Fe and S present in the heme-group of HGB by HPLC isotope dilution ICP-MS. IRMM/IFCC-467 is used for method validation, and then clinical blood samples are measured by the established strategy and HiCN method. The measurable ranges of total HGB were 10.0-240.0 g L-1. Limits of detection via Fe and S were 0.01 and 0.07 g L-1, respectively. The intra-assay imprecision CVs via Fe and S were 0.89-1.35 and 0.99-1.56%, and the interassay CVs were 1.19-2.15 and 1.55-2.55%, respectively. Good agreement was achieved in the method validation. In the comparison with HiCN experiments, the ID-ICP-MS assays via Fe and S showed correlations of r2 = 0.991 and 0.970 against HiCN methods. Moreover, the concentration of transferrin (Tf) was also simultaneously measured. This strategy has potential to serve as a reference measurement procedure for total HGB in whole blood, which could be traceable to SI and does not require toxic derivation reagent.

Abnormalities of retinal structure and microvasculature are associated with cerebral white matter hyperintensities.

BACKGROUND AND PURPOSE: Whilst retinal microvasculature represents cerebral small vessels, the retinal nerve fiber layer is the extended white matter of the brain. The aim was to investigate the correlation between changes in retina and white matter hyperintensities (WMHs). METHODS: Sixty-four candidates with WMHs received an optical coherence tomography angiography examination. WMHs were divided into mild or moderate/severe groups according to the Fazekas score. After imaging the superficial capillary plexus (SCP) and deep capillary plexus (DCP), the microvascular density parameters (vascular perfusion density [VPD], vascular length density [VLD] and fovea avascular zone area) and morphological parameters (vessel diameter index [VDI], fractal dimension [FD] and vessel tortuosity) were identified. A software algorithm measured the thickness of the peripapillary retina nerve fiber layer (PRNFL). RESULTS: Thirty-two were classified as having mild WMHs and 32 were moderate/severe. The median (interquartile range) ages of the two groups were 58 (54-64) and 61 (57-67) years, respectively. A decrease of FD, VPD and VLD in either SCP or DCP appeared with an increased risk of moderate/severe WMHs. Although changes of capillary plexus were not associated with paraventricular WMHs, decreased FD, VPD, VLD and fovea avascular zone area in either SCP or DCP were associated with an increased risk of moderate/severe deep WMHs (DWMHs). Participants with moderate/severe WMHs demonstrated reduced PRNFL thickness, particularly in the DWMHs, compared with mild WMHs. CONCLUSIONS: Abnormalities of retinal microvascular density, morphological parameters and PRNFL thickness are correlated with the incidence of moderate/severe WMHs, particularly the DWMHs, suggesting that arteriosclerosis and hypoperfusion are the causes of DWMHs.

Gag Protein Oriented Supramolecular Nets as Potential HIV Traps.

For HIV/AIDS treatment, the cocktail therapy which uses a combination of anti-retroviral drugs remains the most widely accepted practice. However, the potential drug toxicity, patient tolerability, and emerging drug resistance have limited its long-term efficiency. Here, we design a HIV Gag protein-targeting redox supramolecular assembly (ROSA) system for potential HIV inhibition. An assembling precursor was constructed through conjugation of an oxidation-activatable fluorogenic compound BQA with a selected tetrapeptide GGFF. Since BQA shares a similar structure with the known Gag inhibitor, the precursor could bind to HIV Gag protein with moderate affinity. Moreover, after oxidation, the corresponding nanofibers could bind to Gag protein and trap HIV to realize virus control, thus providing a potential anti-HIV strategy.

From a pro-apoptotic peptide to a lytic peptide: One single residue mutation.

Further discovery and design of new anticancer peptides are important for the development of anticancer therapeutics, and study on the detailed acting mechanism and structure-function relationship of peptides is critical for anticancer peptide design and application. In this study, a novel anticancer peptide ZXR-1 (FKIGGFIKKLWRSKLA) derived from a known anticancer peptide mauriporin was developed, and a mutant ZXR-2 (FKIGGFIKKLWRSLLA) with only one residue difference at the 14th position (Lys→Leu) was also engineered. Replacement of the lysine with leucine made ZXR-2 more potent than ZXR-1 in general. Even with only one residue mutation, the two peptides displayed distinct anticancer modes of action. ZXR-1 could translocate into cells, target on the mitochondria and induce cell apoptosis, while ZXR-2 directly targeted on the cell membranes and caused membrane lysis. The variance in their acting mechanisms might be due to the different amphipathicity and positive charge distribution. In addition, the two Ile-Leu pairs (3-10 and 7-14) in ZXR-2 might also play a role in improving its cytotoxicity. Further study on the structure-function relationship of the two peptides may be beneficial for the design of novel anticancer peptides and peptide based therapeutics.

Isoleucine/leucine residues at "a" and "d" positions of a heptad repeat sequence are crucial for the cytolytic activity of a short anticancer lytic peptide.

Many lytic peptides contain a heptad sequence with leucine or isoleucine residues at "a" and "d" positions. However, their roles in the peptide-induced cytolytic process remain unclear. We have recently reported an anticancer lytic peptide ZXR-2 (FKIGGFIKKLWRSLLA), which contains a shortened zipper-like sequence with Ile/Leu at "a" and "d" positions. To understand the roles of these Ile/Leu residues, a series of analogs were constructed by sequentially replacing the Ile or Leu residue with alanine (Ala). Significant reduction of the cytolytic activity was observed when the Ile (3rd and 7th) and Leu (10th and 14th) residues at the "a" and "d" positions were substituted, while the replacement of the separate Leu (15th) residue had less effect. Based on the quenching of the intrinsic fluorescence of the peptides and their induced surface pressure changes of lipid monolayer, it was conjectured that the peptide ZXR-2 might insert into cell membranes from the C-terminal and to a depth of the W11 position. Accordingly, I3, I7, and L10 residues which mainly exposed in aqueous solution were more responsible for the peptide self-association on cell membranes, while L14, together with L15, might help peptide insert and anchor to cell membranes. These results are significant to elucidate the crucial roles of such Ile/Leu residues at "a" and "d" positions in peptide-peptide and peptide-membrane interactions to exert the membrane disruption activity of lytic peptides. With further understanding about the structure-activity relationship of lytic peptides, it would be helpful for designing novel anticancer lytic peptides.

A novel antimicrobial peptide against dental-caries-associated bacteria.

Dental caries, a highly prevalent oral disease, is primarily caused by pathogenic bacteria infection, and most of them are anaerobic. Herein, we investigated the activity of a designed antimicrobial peptide ZXR-2, and found it showed broad-spectrum activity against a variety of Gram-positive and Gram-negative oral bacteria, particularly the caries-related taxa Streptococcus mutans. Time-course killing assays indicated that ZXR-2 killed most bacterial cells within 5 min at 4 × MIC. The mechanism of ZXR-2 involved disruption of cell membranes, as observed by scanning electron microscopy. Moreover, ZXR-2 inhibited the formation of S. mutans biofilm, but showed limited hemolytic effect. Based on its potent antimicrobial activity, rapid killing, and inhibition of S. mutans biofilm formation, ZXR-2 represents a potential therapeutic for the prevention and treatment of dental caries.

Role of peptide self-assembly in antimicrobial peptides.

Antimicrobial peptides (AMPs) are considered as potential antibiotic substitutes because of their potent activities. Previous studies mainly focused on the effects of peptide charges and secondary structures, but the self-assembly of AMPs was neglected. As more and more researchers notice the roles of peptide self-assembly in AMPs, it has been considered as another important property. In this review, we will discuss the influences of peptide self-assembly on the activity and mode of action, and some specific features it introduces to the AMPs, such as particular responsiveness, improved cell selectivity and stability and sustained release. In addition, some methods to design self-assembling AMPs are primarily discussed. With further understanding about the self-assembling regularity, design of particular self-assembling AMPs will be very helpful for their applications, especially in the fields of drug delivery and biomedical engineering.

An investigation of neutron shielding and activation performances of four types of concrete for carbon ion therapy facility.

Carbon ions have unique physical and biological properties that allow for precise targeting of tumors while minimizing damage to surrounding healthy tissues. The emitted neutrons dominate the radiation field in the treatment room and pose challenges for radiological shielding. Concrete is extensively utilized in the construction of radiotherapy facilities due to its good shielding characteristics, and it can be easily poured into the desired shapes and thickness. The difference in composition of concrete affects the characteristics of neutron attenuation and activation performance. Therefore, the purpose of this study is to clarify the shielding properties and activation performances of four types of concrete for carbon ion therapy facilities. The Monte Carlo method is used to analyze the neutron spectra from thick targets upon carbon ion bombardment. Furthermore, the deep attenuation efficiency of the secondary neutron in different compositions of concrete is discussed. The shielding design is developed to ensure compliance with the prescribed dose limit outside the shielding during operation. Finally, the induced radioactivity in concrete is estimated for both short-term and long-term operation. The produced radionuclides inventories and depth profiling are determined. This study reveals the shielding and radioactivity issue of carbon ion therapy facilities and is expected to aid in the design or construction of similar facilities.

Multi-omics pan-cancer analysis reveals the prognostic values and immunological functions of PPA2, with a spotlight on breast cancer.

Background: Recently, the role of inorganic pyrophosphatase 2 (PPA2) has been remaining merely superficial in many tumors. Hence, the aim was to analyze the potential functions of PPA2 in pan-cancer, focusing on its role in breast cancer. Methods: A systematic pan-cancer analysis conducted primarily utilizing various open databases such as TCGA and GTEx. We explored the clinical value of PPA2 as well as various biological functions, including expression levels and subcellular localization, multi-dimensional immune-correlation analysis, co-expression networks, and gene heterogeneity. In addition, we not only verified the function of PPA2 through cell experiments but also analyzed PPA2 at the single-cell level and its drug sensitivity. Results: PPA2 is abnormally expressed in various tumors, and it is mainly distributed in mitochondria. Furthermore, the indicators (OS, DSS, DFI, and PFI) of analysis hint that PPA2 exhibits significant prognostic value. At the same time, the genomic heterogeneity (including TMB, MSI, MATH, and NEO) of PPA2 in pan-cancer was analyzed. Across multiple tumors, the results showed a close correlation between PPA2 expression levels and different immune signatures (such as immune cell infiltration). All of these indicate that PPA2 could potentially be applied in the guidance of immunotherapy. We also have demonstrated that PPA2 promoted the process of breast cancer. Finally, some potential therapeutic agents (such as Fulvestrant) targeting the abnormal expression of PPA2 are revealed. Conclusion: In conclusion, the results demonstrated the great value of PPA2 in pan-cancer research, as well as its potential as a therapeutic target for breast tumors.

Thrombolysis increases the risk of persistent headache attributed to ischemic stroke: A prospective observational study.

BACKGROUND AND OBJECTIVE: Persistent headache attributed to ischemic stroke (PHPIS) is increasingly acknowledged and was added to the 2018 ICHD-3. Intravenous thrombolysis (IVT) is a common treatment for acute ischemic stroke. It remains unknown whether this treatment influences the occurrence of a persistent poststroke headache. We aimed to describe the incidence and clinical characteristics of persistent headaches occurring after acute ischemic stroke in patients with or without IVT and explore the risk factors. METHODS: A prospective observational study was performed between the 234 individuals who received IVT and 226 individuals without IVT in 5 stroke units from Wuhan, China. Subjects were followed for 6 months after stroke via a structured questionnaire. RESULTS: Age, gender, vascular risk factors, and infarct location/ circulation distribution did not differ between the groups, although IVT group had higher initial NIHSS scores. At the end of the follow-up, 12.0% (55/460) of subjects reported persistent headaches after ischemic stroke. The prevalence of persistent headache was significantly higher in the IVT group than non-IVT group (15.4% vs. 8.4%, p = .021). Patients with younger age (p = .033; OR 0.97; 95% CI 0.939-0.997), female sex (p = .007; OR 2.40; 95% CI 1.269-4.520), posterior circulation infarct (p = .024; OR 2.19; 95% CI 1.110-4.311), and IVT (p = .005; OR 2.51; 95% CI 1.313-4.782) were more likely to develop persistent headache after ischemic stroke. CONCLUSION: The potential influence of IVT should be considered when assessing persistent poststroke headache. Future studies will investigate the underlying mechanisms.

Correlations of Plasma Biomarkers and Imaging Characteristics of Cerebral Small Vessel Disease.

Cerebral small vessel disease (CSVD), which is a group of pathological processes affecting cerebral microvessels, leads to functional loss in the elderly population and mostly presents as cognitive impairment and gait decline. CSVD is diagnosed based on brain imaging biomarkers, but blood biomarkers are of great significance for the early diagnosis and progression prediction of CSVD and have become a research focus because of their noninvasiveness and easy accessibility. Notably, many blood biomarkers have been reported to be associated with CSVD in a relatively large population, particularly serum neurofilament light chain (NfL), which has been regarded as a promising biomarker to track the variation trend in WMH and to predict the further status of white matter hyperintensities (WMH) and lacunar infarcts. And neuro-glio-vascular unit structure and blood-brain barrier function have been proposed as underlying mechanisms of CSVD. The article starts from the neuroimaging markers of CSVD, including recent small subcortical infarcts (RSSI), white matter hyperintensities (WMH), lacunes, cerebral microbleeds (CMB), enlarged perivascular spaces (EPVS), cerebral atrophy, and the combined small vessel disease score, and attempts to systematically review and summarize the research progress regarding the blood biomarkers of CSVD that form the changes in the neuro-glio-vascular unit structure and blood-brain barrier function.

Tea Polyphenol Epigallocatechin Gallate Protects Against Nonalcoholic Fatty Liver Disease and Associated Endotoxemia in Rats via Modulating Gut Microbiota Dysbiosis and Alleviating Intestinal Barrier Dysfunction and Related Inflammation.

Nonalcoholic fatty liver disease (NAFLD) is characterized by fat accumulation and inflammation. Epigallocatechin gallate (EGCG) has been proven to be effective against NAFLD, but its hepatoprotective mechanisms based on the "gut microbiota-barrier-liver axis" are still not fully understood. Herein, the results demonstrated that EGCG effectively ameliorated NAFLD phenotypes and metabolic disorders in rats fed a high-fat diet (HFD), and inhibited intestinal barrier dysfunction and inflammation, which is also supported in the experiment of Caco-2 cells. Moreover, EGCG could restore gut microbiota diversity and composition, particularly promoting beneficial microbes, including short-chain fatty acids (SCFAs) producers, such as Lactobacillus, and suppressing Gram-negative bacteria, such as Desulfovibrio. The microbial modulation raised SCFA levels, decreased lipopolysaccharide levels, inhibited the TLR4/NF-κB pathway, and strengthened intestinal barrier function via Nrf2 pathway activation, thereby alleviating liver steatosis and inflammation. Spearman's correlation analysis showed that 24 key OTUs, negatively or positively associated with NAFLD and metabolic disorders, were also reshaped by EGCG. Our results suggested that a combinative improvement of EGCG on gut microbiota dysbiosis, intestinal barrier dysfunction, and inflammation might be a potential therapeutic target for NAFLD.

Self-assembly of pH and calcium dual-responsive peptide-amphiphilic hydrogel.

Peptide-based hydrogels have gained much interest for biomedical applications as a result of their biocompatibility. Herein, we reported a synthetic pH-sensitive and calcium-responsive peptide-amphiphilic hydrogel. The sequences of the peptide amphiphiles were derived from the repeat-in-toxin (RTX) motif. At a certain peptide-amphiphile concentration, self-assembly was accompanied by the formation of a rigid, viscoelastic hydrogel at low pH or the presence of calcium ions. Circular dichroism spectra showed that the peptide amphiphiles adopted beta-sheet structure. Meanwhile, as revealed by transmission electron microscopy, the peptide-amphiphile self-assembly was accompanied by the formation of long interconnected nanofibrillar superstructure. Material properties of the resulting peptide-amphiphile hydrogel were characterized using oscillatory sheer rheology, and the storage modulus (G') was found to be one order of magnitude higher than the loss modulus (G"), indicating a moderately rigid viscoelastic material. Furthermore, with systematical residue substitution, it was found that the aspartic acid within the repeat-in-toxin sequence of peptide amphiphiles was responsible for the pH and calcium selectivity. The environmental responsiveness, secondary structure, morphology, and mechanical nature of the peptide-amphiphile hydrogel make it a possible material candidate for biomedical and engineering application.

Differences in Gray Matter Volume in Cerebral Small Vessel Disease Patients with and without Sleep Disturbance.

Recently, there has been increased interest in the relationship between cerebral small vessel disease (CSVD) and circadian rhythm disruption, particularly sleep disturbance. However, the neural mechanism of sleep disturbance in CSVD patients remains poorly understood. The purpose of this study is to explore the gray matter alterations in CSVD patients with and without sleep disturbance. 59 patients with CSVD and 40 healthy controls (HC) were recruited for the present study. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. CSVD patients were categorized into either the good sleepers group (CSVD-GS, n = 23) or the poor sleepers group (CSVD-PS, n = 36) based on PSQI score. Voxel-based morphometry (VBM) analysis was used to assess differences in gray matter volume (GMV) between groups. Multivariate regression analyses were performed to investigate the relationships between sleep quality, GMV, and white matter hyperintensities (WMH). We observed GMV differences between the three groups in the bilateral caudate, right thalamus, bilateral calcarine cortex, left precentral gyrus, right orbitofrontal cortex, left cingulate gyrus, and right sub-gyral temporal lobe. Additionally, the CSVD-PS group exhibited decreased GMV in the bilateral calcarine cortex yet increased GMV in the right caudate compared to the CSVD-GS group. In fully adjusted models, GMV of the right caudate and bilateral calcarine cortex was associated with sleep quality in CSVD patients. The present study revealed structural brain alterations in CSVD patients with sleep disturbance. These findings may provide novel insights into the neural mechanisms of sleep disturbance in CSVD.

Consumer Liking of Turnip Cooked by Different Methods: The Influence of Sensory Profile and Consumer Bitter Taste Genotype.

Brassica vegetables are bitter, predominantly because they contain bitter-tasting glucosinolates. Individuals with high bitter taste sensitivity are reported to have lower consumption of bitter vegetables. Studies reported that cooking methods can alter the sensory characteristics of vegetables, increasing acceptability. This study investigated consumer liking of turnip cooked by four methods (boiled-pureed, roasted, steamed-pureed and stir-fried) and related this to sensory characteristics. Additionally, this study examined the effect of the bitter taste genotype on taste perception and liking of the cooked turnip samples. Participants (n = 74) were recruited and the TAS2R38 genotype was measured. Liking, consumption intent, perception of bitterness and sweetness of turnip were evaluated. A sensory profile of the cooked turnip variants was also determined by a trained sensory panel. There were significant differences in the overall (p = 0.001) and taste (p = 0.002) liking between cooking methods. Turnip liking was increased when preparation led to sweeter taste profiles. The TAS2R38 genotype had a significant effect on bitter perception (p = 0.02) but did not significantly affect taste liking. In conclusion, the cooking method affected turnip liking, and the bitter perception in turnip was influenced by the TAS2R38 genotype. However, taste sensitivity did not predict turnip liking in this UK adult cohort.

Type A personality, sleep quality, and cerebral small vessel disease: investigating the mediating role of sleep in a community-based study.

Purpose: Type A behavior pattern (TABP) is a personality type characterized by rapid speech, impatience, competition, and hostility. Asymptomatic cerebral small vessel disease (CSVD) is often endemic in older adults. Individuals with TABP commonly experience suboptimal sleep quality, and a correlation exists between sleep disturbances and CSVD. We investigated the relationship between TABP and CSVD markers and further explored the mediating role of sleep quality in the relationship between TABP and CSVD. Methods: A cross-sectional survey included 764 community-dwelling adults aged 55-85 years. The TABP Scale and the Pittsburgh Sleep Quality Index (PSQI) were used to assess personality and sleep quality, respectively. Linear and logistic regression analyses were used to examine relationships between variables of interest. In addition, mediation analyses with bootstrapping were used to test whether sleep quality mediated the relationship between TABP and CSVD. Results: Of the 764 participants [median age 65 (61-69) years, 59.9% female], the population with type A personality accounted for 44.8%. After adjusting for covariates, TABP scores (p = 0.03) and PSQI scores (p < 0.001) were significantly correlated with CSVD. In addition, sleep quality partially mediated the association between type A behavior and CSVD, and the mediating effect was 10.67%. Conclusion: This study showed that type A behavior was a risk factor for CSVD among older community-dwelling adults and that sleep quality mediated the relationship between type A behavior and CSVD. Changing type A behavior may help improve sleep quality, which may in turn reduce the prevalence of CSVD.

Elevated Plasma Oligomeric Amyloid ß-42 Is Associated with Cognitive Impairments in Cerebral Small Vessel Disease.

Due to the heterogeneity of amyloid ß-42 (Aß42) species, the potential correlation between plasma oligomeric Aß42 (oAß42) and cognitive impairments in cerebral small vessel disease (CSVD) remains unclear. Herein, a sandwich ELISA for the specific detection of Aß42 oligomers (oAß42) and total Aß42 (tAß42) was developed based on sequence- and conformation-specific antibody pairs for the evaluation of plasma samples from a Chinese CSVD community cohort. After age and gender matching, 3-Tesla magnetic resonance imaging and multidimensional cognitive assessment were conducted in 134 CSVD patients and equal controls. The results showed that plasma tAß42 and oAß42 levels were significantly elevated in CSVD patients. By regression analysis, these elevations were correlated with the presence of CSVD and its imaging markers (i.e., white matter hyperintensities). Plasma Aß42 tests further strengthened the predictive power of vascular risk factors for the presence of CSVD. Relative to tAß42, oAß42 showed a closer correlation with memory domains evaluated by neuropsychological tests. In conclusion, this sensitive ELISA protocol facilitated the detection of plasma Aß42; Aß42, especially its oligomeric form, can serve as a biosensor for the presence of CSVD and associated cognitive impairments represented by memory domains.

Taste and stability characteristics of two key umami peptides from pufferfish (Takifugu obscurus).

Takifugu obscurus (T. obscurus) is known for its umami taste. Two taste-active peptides, Pro-Val-Ala-Arg-Met-Cys-Arg (PR-7) and Tyr-Gly-Gly-Thr-Pro-Pro-Phe-Val (YV-8), were proved as key compounds that contributed to the typical taste of T. obscurus. However, whether these peptides have the potential as umami supplements is unknown. The purpose of this study was to investigate the taste characteristics of PR-7 and YV-8, as well as stability at different pH values by sensory evaluation, instrumental analysis and quantum chemical calculation. The results indicated that PR-7 and YV-8 presented umami taste at near neutral pH (6.5-8.0) and had umami-enhancing effects. PR-7 also exhibited significant kokumi activity. Additionally, two peptides showed remarkable stability after different pH treatments, especially YV-8; this may be related to its stable structural property. All the results suggest that both peptides have great potential to be applied in complex foods to provide desirable taste, and act as a feasible alternative to monosodium l-glutamate.