Widely targeted metabolomics and flavoromics reveal the effect of Wickerhamomyces anomalus fermentation on the volatile and nonvolatile metabolites of black garlic juice.

Black garlic has a variety of biological activities, but many consumers cannot accept it because of the garlic odor and the bitter taste. In this study, fermentation with yeast Wickerhamomyces anomalus was adopted to improve the flavor of black garlic juice. Although fermentation reduced antioxidant activities, the garlicky odor and bitter taste were weakened. Metabolomic analysis revealed 141 metabolites were significantly differentially regulated. The upregulated metabolites were mainly related to nucleotides, organic acids and their derivatives, while the downregulated metabolites were mainly related to amino acids, lipids and their derivatives. Flavoromics analysis revealed that 137 metabolites were significantly differentially regulated, particularly garlicky and pungent volatiles were significantly downregulated. Correlation analysis indicated that esters are most closely related to nonvolatile metabolites, and lipids degradation was significantly correlated with volatiles. The results indicated that W. anomalus fermentation is an effective strategy to improve the flavor of black garlic juice.

Fecal Carriage of Multidrug-Resistant Organisms Increases the Risk of Hepatic Encephalopathy in Cirrhotic Patients: Insights from Gut Microbiota and Metabolite Features.

Background: Impact of fecal colonization by multidrug-resistant organisms (MDROs) on changes in gut microbiota and associated metabolites, as well as its role in cirrhosis-associated outcomes, has not been thoroughly investigated. Methods: Eighty-eight cirrhotic patients and 22 healthy volunteers were prospectively enrolled with analysis conducted on plasma metabolites, fecal MDROs, and microbiota. Patients were followed for a minimum of one year. Predictive factors for cirrhosis-associated outcomes were identified using Cox proportional hazards regression models, and risk factors for fecal MDRO carriage were assessed using logistic regression model. Correlations between microbiota and metabolic profiles were evaluated through Spearman's rank test. Results: Twenty-nine (33%) cirrhotic patients exhibited MDRO carriage, with a notably higher rate of hepatic encephalopathy (HE) in MDRO carriers (20.7% vs. 3.2%, p = 0.008). Cox regression analysis identified higher serum lipopolysaccharide levels and fecal MDRO carriage as predictors for HE development. Logistic regression analysis showed that MDRO carriage is an independent risk factor for developing HE. Microbiota analysis showed a significant dissimilarity of fecal microbiota between cirrhotic patients with and without MDRO carriage (p = 0.033). Thirty-two metabolites exhibiting significantly different expression levels among healthy controls, cirrhotic patients with and without MDRO carriage were identified. Six of the metabolites showed correlation with specific bacterial taxa expression in MDRO carriers, with isoaustin showing significantly higher levels in MDRO carriers experiencing HE compared to those who did not. Conclusion: Fecal MDRO carriage is associated with altered gut microbiota, metabolite modulation, and an elevated risk of HE occurrence within a year.

Characteristics of the time processing of adults' strongest sustained attentional bias toward neutral infant faces.

Previous studies have shown that adults exhibit the strongest attentional bias toward neutral infant faces when viewing faces with different expressions at different attentional processing stages due to different stimulus presentation times. However, it is not clear how the characteristics of the temporal processing associated with the strongest effect change over time. Thus, we combined a free-viewing task with eye-tracking technology to measure adults' attentional bias toward infant and adult faces with happy, neutral, and sad expressions of the same face. The results of the analysis of the total time course indicated that the strongest effect occurred during the strategic processing stage. However, the results of the analysis of the split time course revealed that sad infant faces first elicited adults' attentional bias at 0 to 500 ms, whereas the strongest effect of attentional bias toward neutral infant faces was observed at 1000 to 3000 ms, peaking at 1500 to 2000 ms. In addition, women and men had no differences in their responses to different expressions. In summary, this study provides further evidence that adults' attentional bias toward infant faces across stages of attention processing is modulated by expressions. Specifically, during automatic processing adults' attentional bias was directed toward sad infant faces, followed by a shift to the processing of neutral infant faces during strategic processing, which ultimately resulted in the strongest effect. These findings highlight that this strongest effect is dynamic and associated with a specific time window in the strategic process.

26.5625 Gbaud PAM-4 short-reach transmission at 75°C using 850 nm VCSELs with strategic oxide guiding layer positioning.

This article presents an all-epitaxy approach to reduce the root mean square spectral width (ΔλR M S) of 850 nm oxide-confined vertical cavity surface-emitting lasers (VCSELs) with a large aperture of 7 µm through strategic optimization of the oxide guiding layer within the epitaxy structure. At 75°C, the VCSEL demonstrates a ΔλR M S of ∼0.3 nm at a bias current of 7.5 mA. Furthermore, the VCSEL achieves successful transmission of 26.5625 Gbaud PAM-4 modulation over a short-reach (SR) OM4 fiber link while maintaining a TDECQ budget below the 4.5 dB specified by 50G IEEE Ethernet standards.

Monolithically integrated 940†nm VCSELs on bulk Ge substrates.

This research successfully developed an independent Ge-based VCSEL epitaxy and fabrication technology route, which set the stage for integrating AlGaAs-based semiconductor devices on bulk Ge substrates. This is the second successful Ge-based VCSEL technology reported worldwide and the first Ge-based VCSEL technology with key details disclosed, including Ge substrate specification, transition layer structure and composition, and fabrication process. Compared with the GaAs counterparts, after epitaxy optimization, the Ge-based VCSEL wafer has a 40% lower surface root-mean-square roughness and 72% lower average bow-warp. After device fabrication, the Ge-based VCSEL has a 10% lower threshold current density and 19% higher maximum optical differential efficiency than the GaAs-based VCSEL.

Factors affecting vancomycin-resistant Enterococcus faecium colonization of in-hospital patients in different wards.

Objectives: The prevalence of vancomycin-resistant Enterococcus faecium (VRE) infection at a medical center in Eastern Taiwan rose to 80.6%, exceeding the average prevalence of 55.6% among all medical centers nationwide during the same period. In recent years, the number of cases of VRE infection detected among hospitalized patients has increased annually. However, most of these patients in different wards are asymptomatic carriers. Therefore, restricting active screening to high-risk units will not improve the current situation, and it is necessary to review the risk factors for VRE colonization to provide a reference for future infection control policies. Materials and Methods: Between 2014 and 2019, there were 3188 VRE-positive cultures reported at our institution, as per the electronic medical records system. Results: In the medical and surgical wards, patients who received penicillin (odds ratios [ORs]: 2.84 and 4.16, respectively) and third-generation cephalosporins (ORs: 3.17 and 6.19, respectively) were at higher risk of VRE colonization. In intensive care units, the use of carbapenems (OR: 2.08) was the most significant variable. Conclusion: This study demonstrated that the risk factors for VRE colonization differed between wards. Thus, policies should be established according to the attributes of patients in each ward, and active screening tests should be performed according to individual risks, instead of a policy for comprehensive mass screening.

25 Gb/s NRZ transmission at 85°C using a high-speed 940 nm AlGaAs oxide-confined VCSEL grown on a Ge substrate.

In this Letter, we present a comprehensive analysis of the high-speed performance of 940 nm oxide-confined AlGaAs vertical-cavity surface-emitting lasers (VCSELs) grown on Ge substrates. Our demonstration reveals a pronounced superiority of Ge-based VCSELs in terms of thermal stability. The presented Ge-VCSEL has a maximum modulation bandwidth of 16.1 GHz and successfully realizes a 25 Gb/s NRZ transmission at 85 ∘C. The experimental results underscore the significance and potential of Ge-VCSELs for applications requiring robust performance in high-temperature environments, laying the cornerstone for the future development of VCSEL devices.

Targeting phosphorylation circuits on CREB and CRTCs as the strategy to prevent acquired skin hyperpigmentation.

Background: The cAMP response element-binding protein (CREB) and CREB-regulated transcription coactivators (CRTCs) cooperate in the transcriptional activation of microphthalmia-associated transcription factor subtype M (MITF-M) that is a master regulator in the biogenesis, pigmentation and transfer of melanosomes at epidermal melanocytes. Here, we propose the targeting of phosphorylation circuits on CREB and CRTCs in the expression of MITF-M as the rationale to prevent skin hyperpigmentation by elucidating the inhibitory activity and mechanism of yakuchinone A (Yaku A) on facultative melanogenesis. Methods: We employed human epidermal melanocyte cell, mouse skin, and mouse melanoma cell, and applied Western blotting, reverse transcription-polymerase chain reaction, immunoprecipitation and confocal microscopy to conduct this study. Results: This study suggested that α-melanocyte stimulating hormone (α-MSH)-induced melanogenic programs could switch on the axis of protein kinase A-salt inducible kinases (PKA-SIKs) rather than that of PKA-AMP activated protein kinase (PKA-AMPK) during the dephosphorylation of CRTCs in the expression of MITF-M. SIK inhibitors rather than AMPK inhibitors stimulated melanin production in melanocyte cultures in the absence of extracellular melanogenic stimuli, wherein SIK inhibitors increased the dephosphorylation of CRTCs but bypassed the phosphorylation of CREB for the expression of MITF-M. Treatment with Yaku A prevented ultraviolet B (UV-B)-irradiated skin hyperpigmentation in mice and inhibited melanin production in α-MSH- or SIK inhibitor-activated melanocyte cultures. Mechanistically, Yaku A suppressed the expression of MITF-M via dually targeting the i) cAMP-dependent dissociation of PKA holoenzyme at the upstream from PKA-catalyzed phosphorylation of CREB coupled with PKA-SIKs axis-mediated dephosphorylation of CRTCs in α-MSH-induced melanogenic programs, and ii) nuclear import of CRTCs after SIK inhibitor-induced dephosphorylation of CRTCs. Conclusions: Taken together, the targeting phosphorylation circuits on CREB and CRTCs in the expression of MITF-M could be a suitable strategy to prevent pigmentary disorders in the skin.

Mac-2-Binding Protein Glycosylation Isomer to Albumin Ratio Predicts Bacterial Infections in Cirrhotic Patients.

INTRODUCTION: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis, but little is known about its role in cirrhosis-associated clinical outcomes. This study aimed to investigate the predictive role of M2BPGi in cirrhosis-associated complications. METHODS: One hundred and forty-nine cirrhotic patients were retrospectively enrolled. Patients were followed up for 1 year, and cirrhosis-associated clinical events were recorded. Receiver operating characteristic curve (ROC) analysis was used to establish the values of the predictive models for cirrhotic outcomes, and Cox proportional hazards regression models were used to identify predictors of clinical outcomes. RESULTS: Sixty (40.3%) patients experienced cirrhosis-associated clinical events and had higher M2BPGi levels compared to those without events (8.7 vs. 5.1 cutoff index, p < 0.001). The most common cirrhosis-associated complications were bacterial infections (24.2%). On ROC analysis, M2BPGi to albumin ratio (M2BPGi/albumin) had comparable discriminant abilities for all cirrhosis-associated events (area under the ROC curve [AUC] = 0.74) compared with M2BPGi, Child-Pugh, model for end-stage liver disease, albumin-bilirubin scores, and neutrophil-to-lymphocyte ratio and was superior to M2BPGi alone for all bacterial infectious events (AUC = 0.80). Cox regression analysis revealed that the M2BPGi/albumin, but not M2BPGi alone, independently predicted all cirrhosis-associated events (hazard ratio [HR] = 1.34, p = 0.038) and all bacterial infectious events (HR = 1.51, p = 0.011) within 1 year. However, M2BPGi/albumin did not predict other cirrhotic complications and transplant-free survival. DISCUSSION/CONCLUSION: M2BPGi/albumin might serve as a potential prognostic indicator for patients with cirrhosis, particularly for predicting bacterial infections.

Paranasal sinus occupancy assessed from magnetic resonance images-associations with clinical indicators in patients with systemic lupus erythematosus.

OBJECTIVES: Nasal, paranasal sinus and mucosal disorders are common symptoms in autoimmune rheumatic diseases. Soft tissue changes and fluid accumulation in the osteomeatal complexes and paranasal sinuses manifest as opaqueness on radiological images which can be assessed using visual scoring and computational methods on CT scans, but their results do not always correlate. Using MRI, we investigate the applicability of different image analysis methods in SLE. METHODS: We assessed paranasal sinus opaqueness on MRI from 51 SLE patients, using three visual scoring systems and expert-delineated computational volumes, and examined their association with markers of disease activity, inflammation, endothelial dysfunction and common small vessel disease (SVD) indicators, adjusting for age and sex-at-birth. RESULTS: The average paranasal sinus volume occupation was 4.55 (6.47%) [median (interquartile range) = 0.67 (0.25-2.65) ml], mainly in the maxillary and ethmoid sinuses. It was highly correlated with Lund-Mackay (LM) scores modified at 50% opaqueness cut-off (Spearman's ρ: 0.71 maxillary and 0.618 ethmoids, P < 0.001 in all), and with more granular variations of the LM system. The modified LM scores were associated with SVD scores (0: B = 5.078, s.e. = 1.69, P = 0.0026; 2: B = -0.066, s.e. = 0.023, P = 0.0045) and disease activity (anti-dsDNA: B = 4.59, s.e. = 2.22, P = 0.045; SLEDAI 3-7: 2.86 < B < 4.30; 1.38 < s.e. < 1.63; 0.0083 ≤ P ≤ 0.0375). Computationally derived percent opaqueness yielded similar results. CONCLUSION: In patients with SLE, MRI computational assessment of sinuses opaqueness and LM scores modified at a 50% cut-off may be useful tools in understanding the relationships among paranasal sinus occupancy, disease activity and SVD markers.

Effect of peach gum polysaccharide on the rheological and 3D printing properties of gelatin-based functional gummy candy.

Excellent 3D printing materials must exhibit good extrudability and supportability, but these two characteristics are often contradictory. In this study, peach gum polysaccharide (PGP) was added to gelatin to prepare a 3D-printed functional gummy candy encapsulating curcumin. Rheology tests indicated that adding PGP could effectively improve the apparent viscosity and thermal stability and consequently improve the 3D printability and supportability of the products. When PGP addition was 6 %, the printing accuracy was higher than 90 %. Texture and microstructure analysis further revealed that PGP addition promoting a dense gel structure formed and the water holding capacity and supportability of gel materials were enhanced. Furthermore, the in vitro gastrointestinal digestion tests showed that after 6 h of simulated gastrointestinal fluid digestion, the retention rate of curcumin was nearly 80 %. The above results indicated that the composite gel of PGP and gelatin is a good 3D printing base material for nutrient delivery.

Effects of grafting methods and raw materials on the physicochemical properties and biological activities of phenolic acids grafted oat ß-glucan.

Phenolic acids are commonly used as food biological preservatives. Grafting phenolic acids onto polysaccharides could effectively enhance their biological activities and environmental stability to varying degrees. However, grafting methods and raw materials could affect the physical properties and biological activities of the phenolic acid-grafted polysaccharides. In this study, caffeic acid (CA) and gallic acid (GA) were grafted onto oat ß-glucan (OG) and hydrolyzed oat ß-glucan (OGH) through N,N'-carbonyldiimidazole-mediated (CDI) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride coupling N-hydroxysuccinimide (EDC/NHS) methods. Graft modification decreased the crystallinity and thermal stability of the conjugates, but retained good bioactivities for the conjugates. The antioxidant and bacteriostatic activities of the conjugates prepared by the EDC method were better than those of the CDI method, and the OGH-conjugates showed better biological activities than OG-conjugates. EDC-GAOGH showed best DPPH (89.78%) and ABTS (92.32%) scavenging activities. The inhibitory effect of EDC-GAOGH on Escherichia coli was significantly better than that of EDC-CAOGH, but for Staphylococcus aureus, the results are opposite, which indicating that different phenolic acid grafting products have different inhibitory effects on pathogenic microbes. In general, grafting phenolic acids onto OGH using EDC method is an effective strategy for preparing food biological preservative.

Zone-addressable 20 × 20 940 nm VCSEL array with a 5-bit binary number pattern.

This article presents a monolithically zone-addressable 20 × 20 940 nm vertical-cavity surface-emitting laser (VCSEL) array with a binary number pattern design for sensing applications. The emitters in this VCSEL array have a uniquely designed binary pattern design, with each row representing a 5-bit pattern designed to aid pattern-matching algorithms to deduce the shape and depth information efficiently. Approximately 200 VCSELs are arranged in four individually addressable light-emitting zones, with ∼50 emitters in each zone. Each zone generates laser pulses up to 7.2 W in peak power.

Nickel-Catalyzed Selective C(sp2 )-F Bond Alkylation of Industrially Relevant Hydrofluoroolefin HFO-1234yf.

The selective transition-metal catalyzed C-F bond functionalization of inexpensive industrial fluorochemicals represents one of the most attractive approaches to valuable fluorinated compounds. However, the selective C(sp2 )-F bond carbofunctionalization of refrigerant hydrofluoroolefins (HFOs) remains challenging. Here, we report a nickel-catalyzed selective C(sp2 )-F bond alkylation of HFO-1234yf with alkylzinc reagents. The resulting 2-trifluoromethylalkenes can serve as a versatile synthon for diversified transformations, including the anti-Markovnikov type hydroalkylation and the synthesis of bioactive molecule analogues. Mechanistic studies reveal that lithium salt is essential to promote the oxidative addition of Ni0 (Ln ) to the C-F bond; the less electron-rich N-based ligands, such as bipyridine and pyridine-oxazoline, feature comparable or even higher oxidative addition rates than the electron-rich phosphine ligands; the strong σ-donating phosphine ligands, such as PMe3 , are detrimental to transmetallation, but the less electron-rich and bulky N-based ligands, such as pyridine-oxazoline, facilitate transmetallation and reductive elimination to form the final product.

Paranasal sinuses opacification on magnetic resonance imaging in relation to brain health in sporadic small vessel disease - Systematic review and pilot analysis.

BACKGROUND: The paranasal sinus mucosal thickening, visible in magnetic resonance imaging (MRI), maybe a source of inflammation in microvessels, but its relationship with small vessel disease (SVD) is unclear. We reviewed the literature and analysed a sample of patients with sporadic SVD to identify any association between paranasal sinus opacification severity and SVD neuroimaging markers. METHODS: We systematically reviewed MEDLINE and EMBASE databases up to April 2020 for studies on paranasal sinus mucosal changes in patients with SVD, cerebrovascular disease (CVD), and age-related neurodegenerative diseases. We analysed clinical and MRI data from 100 participants in a prospective study, the Mild Stroke Study 3 (ISRCTN 12113543) at 1-3, 6 and 12 months following a minor stroke to test key outcomes from the literature review. We used multivariate linear regression to explore associations between modified Lund-Mackay (LM) scores and brain, white matter hyperintensities (WMH), enlarged perivascular spaces (PVS) volumes at each time point, adjusted for baseline age, sex, diabetes, hypercholesterolaemia, hypertension and smoking. RESULTS: The literature review, after screening 3652 publications, yielded 11 primary studies, for qualitative synthesis with contradictory results, as positive associations/higher risk from 5/7 CVD studies were contradicted by the two studies with largest samples, and data from dementia studies was equally split in their outcome. From the pilot sample of patients analysed (female N = 33, mean age 67.42 (9.70) years), total LM scores had a borderline negative association with PVS in the centrum semiovale at baseline and 6 months (B = -0.25, SE = 0.14, p = 0.06) but were not associated with average brain tissue, WMH or normal-appearing white matter volumes. CONCLUSION: The inconclusive results from the literature review and empirical study justify larger studies between PVS volume and paranasal sinuses opacification in patients with sporadic SVD.

BAG3 Overexpression Attenuates Ischemic Stroke Injury by Activating Autophagy and Inhibiting Apoptosis.

BACKGROUND: The ubiquitin-proteasome system (UPS) and autophagy are 2 major protein degradation pathways in eukaryotic cells. We previously identified a switch from UPS to autophagy with changes in BAG3 (B-cell lymphoma 2-associated-athanogene 3) expression after cerebral ischemia in mice. BAG3 is an antiapoptotic-cochaperone that is directly involved in cellular protein quality control as a mediator for selective macroautophagy. Here, we aimed to investigate the role of BAG3 in ischemic stroke. METHODS: Middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation were used to mimic cerebral ischemia in vivo and in vitro. The UPS inhibitor MG132 and autophagy inhibitor 3-MA (3-methyladenine) were administered to mice to identify how BAG3 was involved after MCAO/R. Adeno-associated virus and lentiviral vector were used to regulate BAG3 expression in vivo and in vitro, respectively. Behavioral tests, 2,3,5-triphenyltetrazolium chloride staining, and Hematoxylin & Eosin staining were performed to evaluate cerebral injury following MCAO/R, and a Cell Counting kit-8 assay was conducted to assess oxygen-glucose deprivation/reoxygenation-induced injury in cells. Brain tissues and cell lysates were collected and analyzed for UPS activation, autophagy, and apoptosis. RESULTS: The UPS inhibitor alleviated MCAO injury in mice and increased autophagy and BAG3 expression, whereas the autophagy inhibitor exacerbated MCAO/R-induced injury. In addition, BAG3 overexpression significantly improved neurological outcomes, reduced infarct volume in vivo, and enhanced cell survival by activating autophagy and suppressing apoptosis in vitro. CONCLUSIONS: Our findings indicate that BAG3 overexpression activates autophagy and inhibits apoptosis to prevent cerebral ischemia/reperfusion and hypoxia/reoxygenation injury, suggesting a potential therapeutic benefit of BAG3 expression in cerebral ischemia.

Effect of honeysuckle leaf extract on the physicochemical properties of carboxymethyl konjac glucomannan/konjac glucomannan/gelatin composite edible film.

Honeysuckle leaves are rich in bioactive ingredients, but often considered as agro-wastes. In this study, honeysuckle leaf extract (HLE) was added to the carboxymethyl konjac glucomannan/konjac glucomannan/gelatin composite edible film (CMKH). Compared to films without HLE addition (CMK), the water vapor barrier properties of CMKH slightly decreased, but the transmittance of the CMKH films in UV region (200-400 nm) as low as zero. The elongation at break of CMKH film was 1.39 âˆ¼ 1.5 fold higher than those of CMK films. The DPPH and ABTS scavenging activity of CMKH-Ⅱ was 85.75% and 90.93%, respectively, which is similar to the equivalent content of Vc. The inhibition rate of CMKH-Ⅰ and CMKH-Ⅱ against Escherichia coli and Listeria monocytogenes were close to 90%, and the inhibition rate against Staphylococcus aureus were up to 96%. The results emphasized that the composite film containing 25% (v/v) HLE has potential application value in food preservation.

Retraction notice to "Betulinic acid downregulates expression of oxidative stress-induced lipoprotein lipase via PKC/ERK/c-Fos pathways in RAW264.7 macrophages" [Biochimie 119C (2015) 192-203].

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. Concerns raised by Dr. Sander Kersten in PubPeer pointed out that Figs. 6.1B and 6.2B of this paper were different figures but the legends and Western blots were identical; the quantification was also seen to be different between the two figures. Shortly afterwards, the authors asked to publish a corrigendum for part B of Fig. 6.1, including images of western blots and associated bar plots. Subsequently, the journal conducted an investigation and found evidence that there had been improper manipulation and duplication of images in Fig. 2 E, 6.2 B, 5 A and and 6.2 D, as shown by the reuse of several western blot bands with approximately 180° rotation in each case. After raising the complaint with the authors, the corresponding author agreed that the paper should be retracted. The authors apologise to the readers of the journal.