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The purpose of this article is to examine the impact of covid on the U.S. exchange rate and the oil market. Previous scholarly studies have shown that currency and oil markets have a significant impact on the global economy, so the article wants to investigate whether the relationship between the two will be stronger under the influence of pandemics and the impact on each. By building a table of daily U.S. to RMB exchange rates during the pandemic, and a chronologically derived stock index with corresponding graphs and literature data, it concludes that currency exchange rates are an irreplaceable determinant of stock market returns. The 0.534% depreciation of the U.S. dollar under the impact of the epidemic im-proved the average stock market return.

The metabolic score for insulin resistance (METS-IR) is a recently developed parameter for screening of metabolic disorder. However, the association between METS-IR and risk of hypertension in general adult population remains not fully determined. A meta-analysis was therefore performed. Observational studies evaluating the association between METS-IR and hypertension in adults were retrieved by searching PubMed, Embase, and Web of Science databases from inception to October 10, 2022. A random-effects model, which incorporates the potential influence of heterogeneity, was used to pool the results. Eight studies with 305 341 adults were included in the meta-analysis, and 47 887 (15.7%) of them had hypertension. Pooled results showed that a higher METS-IR was associated with hypertension after adjusting for multiple conventional risk factors [relative risk (RR) for highest versus lowest category of METS-IR: 1.67, 95% confidence interval (CI): 1.53 to 1.83, p0.05). Results of meta-analysis with METS-IR analyzed in continuous variables also showed that METS-IR was associated with the risk of hypertension (RR for 1-unit increment of METS-IR: 1.15, 95% CI: 1.08 to 1.23, p

MN mice models were induced by C-BSA, and we found that acidic stigma maydis polysaccharides maintained the integrity of the glomerular filtration barrier by promoting slit diaphragm proteins expression and PI3K/AKT signaling.

Membranous nephropathy (MN) is a chronic kidney disease and a precursor to end-stage kidney disease. In this study, we evaluated the potential protective effects of acidic and neutral

We compared antioxidant activity of the synthetic peptide Val-Leu-Leu-Tyr-Gln-Asp-His-Cys-His (VLLYQDHCH), sea cucumber peptide Val-Leu-Leu-Tyr (VLLY) and pine seed peptide Gln-Asp-His-Cys-His (QDHCH). The structure–activity relationship was analyzed based on radical scavenging ability and Raman, circular dichroism (CD) and nuclear magnetic resonance spectroscopy (NMR). Based on RP-HPLC, the contents of peptides in simulated gastrointestinal tract and digestive juices in rat intestinal sac were determined, and their absorption stability were explored. These results showed that the DPPH clearance rate of VLLYQDHCH was 45.90% higher than the sum of VLLY and QDHCH at 3 mmol/L. The α-helix, β-sheet and random coil of VLLYQDHCH increased, β-turn decreased, and the active hydrogen site shifted. After simulated digestion and absorption, the retention rate of VLLYQDHCH was 80.86 ± 0.88% in simulated stomach and 45.75 ± 0.97% in simulated intestine. There was no significant difference in the absorption rates of the three peptides (P > 0.05). This research provided a new idea for the development of safe and green food-derived animal-plant protein antioxidant peptides. GRAPHIC ABSTRACT: [Image: see text]

Modern cold seeps are of fluctuant flux, which could result in variabilities of geochemical archives through intensively influencing the redox condition in pore fluids. However, the geochemical archives are not fully understood when the redox condition changes. Here, tubular carbonates from the Shenhu Sea Area were used to reconstruct the formation environment and redox conditions. The moderately negative δ13C values of the carbonates (−40.1‰ to −30.8‰, VPDB) indicate a mixed carbon source of thermogenic and biogenic methane. The low δ18O values (−2.7‰ to 1.0‰, VPDB) suggest a type of 18O-depleted pore fluid possibly influenced by gas hydrate formation. Co-variation of MoEF, WEF, CoEF, and CrEF suggests that high Fe contents in the rims of samples R1 and R2 are induced by Fe (oxyhydr)oxidation enrichment, while the positive correlation between MoEF and Mn/Al ratio indicates that high Mn contents in the rims of samples R3 and R4 are induced by Mn (oxyhydr)oxidation enrichment. The occurrence of Fe or Mn enrichment in the rims and the absence of Fe/Mn enrichment in the cores suggest Fe/Mn (oxyhydr)oxides forming in pore fluid rather than in bottom seawater. The carbonate phases of the rims enriched in Fe (oxyhydr)oxides are dominated by high magnesium calcite, while those of the rims enriched in Mn (oxyhydr)oxides are dominated by aragonite. The occurrence of Fe or Mn (oxyhydr)oxides corresponds to the previously proposed formation depth for the carbonate phase. The occurrence of dissolution textures in these rims indicates episodic oxic conditions, which would facilitate Fe2+/Mn2+ oxidation. We suppose that the Fe2+ and Mn2+ could be supplied through fluid seepage or diffusion from underlying sediments when the flux decreased. Similar archives may be applied to qualitatively reflect the changes of redox conditions in seep systems. Similar scenarios may help us understand the geochemical records in seeps of fluctuant flux.

Oxidative stress promotes tissue injury in the central nervous system in neurological disorders such as multiple sclerosis (MS). To protect against this, antioxidant enzymes including superoxide dismutase-1 (SOD1), heme oxygenase-1 (HO-1), peroxiredoxin-5 (PRDX5) and glutathione peroxidase-4 (GPX4) may be upregulated. However, whether antioxidant enzyme elevation in mouse models of neurodegeneration corresponds to their expression in human diseases such as MS requires investigation. Here, we analyzed and compared the expression of SOD1, HO-1, PRDX5 and GPX4 in the murine spinal cord of three models of MS: focal lesions induced by (1) oxidized phosphatidylcholine or (2) lysophosphatidylcholine (lysolecithin), and (3) diffuse lesions of experimental autoimmune encephalomyelitis. Notably, CD68+ microglia/macrophages were the predominant cellular populations that expressed the highest levels of the detected antioxidant enzymes. Overall, the expression patterns of antioxidant enzymes across the models were similar. The increase of these antioxidant enzymes was corroborated in MS brain tissue using spatial RNA sequencing. Collectively, these results show that antioxidant capacity is relatively conserved between mouse models and MS lesions, and suggest a need to investigate whether the antioxidant elevation in microglia/macrophages is a protective response during oxidative injury, neurodegeneration, and MS.

In this study, PEF-induced steric configuration changes of the peptide Lys-Asp-His-Cys-His (KDHCH), proposed as the mechanism for its antioxidant activity enhancement induced by PEF treatments, were investigated using spectral and chromatographic methods. While no primary structure changes were observed, the secondary structure of KDHCH changed with a significant decrease in the level of α-helix from 3.1 to 1.7% (P < 0.05). A left chemical shift of the active hydrogen in hydroxyl and changes in connectivity between hydrogen protons were also identified, which may be caused by the steric configuration changes. The PEF treatment also decreased the zeta potential and size distribution which might result from the degradation of the peptide complex by PEF processing. These findings suggest that PEF treatment of the peptide solution led to a structural change, which may have enhanced exposure of active sites responsible for the antioxidant activity of the peptide.

Aging is a significant risk factor associated with the progression of central nervous system (CNS) neurodegenerative diseases including multiple sclerosis (MS). Microglia, the resident macrophages of the CNS parenchyma, are a major population of immune cells that accumulate in MS lesions. While they normally regulate tissue homeostasis and facilitate the clearance of neurotoxic molecules including oxidized phosphatidylcholines (OxPC), their transcriptome and neuroprotective functions are reprogrammed by aging. Thus, determining the factors that instigate aging associated microglia dysfunction can lead to new insights for promoting CNS repair and for halting MS disease progression. Through single cell RNA sequencing, we identifiedLgals3,which encodes for galectin-3 (Gal3), as an age upregulated gene by microglia responding to OxPC. Consistently, excess Gal3 accumulated in OxPC and lysolecithin induced focal spinal cord white matter lesions of middle-aged mice compared to young mice. Gal3 was also elevated in mouse experimental autoimmune encephalomyelitis lesions and more importantly in MS brain lesions from 2 male and 1 female individuals. While Gal3 delivery alone into the mouse spinal cord did not induce damage, its co-delivery with OxPC increased cleaved caspase 3 and IL-1β within white matter lesions and exacerbated OxPC induced injury. Conversely, OxPC mediated neurodegeneration was reduced in Gal3-/-mice compared to Gal3+/+mice. Thus, Gal3 is associated with increased neuroinflammation and neurodegeneration and its overexpression by microglia/macrophages may be detrimental for lesions within the aging CNS.SIGNIFICANCE STATEMENT:Aging accelerates the progression of neurodegenerative diseases such as multiple sclerosis (MS). Understanding the molecular mechanisms of aging that increases the susceptibility of the central nervous system (CNS) to damage could lead to new strategies to manage MS progression. Here, we highlight that microglia/macrophage associated galectin-3 (Gal3) was upregulated with age exacerbated neurodegeneration in the mouse spinal cord white matter and in MS lesions. More importantly, co-injection of Gal3 with oxidized phosphatidylcholines (OxPC), which are neurotoxic lipids found in MS lesions, caused greater neurodegeneration compared to injection of OxPC alone, whereas genetic loss of Gal3 reduced OxPC damage. These results demonstrate that Gal3 overexpression is detrimental to CNS lesions and suggest its deposition in MS lesions may contribute to neurodegeneration.

BackgroundInflammation-exacerbated secondary brain injury and limited tissue regeneration are barriers to favourable prognosis after intracerebral haemorrhage (ICH). As a regulator of inflammation and lipid metabolism, Liver X receptor (LXR) has the potential to alter microglia/macrophage (M/M) phenotype, and assist tissue repair by promoting cholesterol efflux and recycling from phagocytes. To support potential clinical translation, the benefits of enhanced LXR signalling are examined in experimental ICH.MethodsCollagenase-induced ICH mice were treated with the LXR agonist GW3965 or vehicle. Behavioural tests were conducted at multiple time points. Lesion and haematoma volume, and other brain parameters were assessed using multimodal MRI with T2-weighted, diffusion tensor imaging and dynamic contrast-enhanced MRI sequences. The fixed brain cryosections were stained and confocal microscopy was applied to detect LXR downstream genes, M/M phenotype, lipid/cholesterol-laden phagocytes, oligodendrocyte lineage cells and neural stem cells. Western blot and real-time qPCR were also used. CX3CR1CreER: Rosa26iDTRmice were employed for M/M-depletion experiments.ResultsGW3965 treatment reduced lesion volume and white matter injury, and promoted haematoma clearance. Treated mice upregulated LXR downstream genes including ABCA1 and Apolipoprotein E, and had reduced density of M/M that apparently shifted from proinflammatory interleukin-1β+to Arginase1+CD206+regulatory phenotype. Fewer cholesterol crystal or myelin debris-laden phagocytes were observed in GW3965 mice. LXR activation increased the number of Olig2+PDGFRα+precursors and Olig2+CC1+mature oligodendrocytes in perihaematomal regions, and elevated SOX2+or nestin+neural stem cells in lesion and subventricular zone. MRI results supported better lesion recovery by GW3965, and this was corroborated by return to pre-ICH values of functional rotarod activity. The therapeutic effects of GW3965 were abrogated by M/M depletion in CX3CR1CreER: Rosa26iDTRmice.ConclusionsLXR agonism using GW3965 reduced brain injury, promoted beneficial properties of M/M and facilitated tissue repair correspondent with enhanced cholesterol recycling.

Medical students in China and other non-English speaking countries are susceptible to English as a Foreign Language (EFL) writing anxiety. English writing is not only a vital component tested for admission to postgraduate and doctoral programs, but it is also critical for the publication of academic papers. Although there is mounting evidence indicating relationships between anxiety, self-esteem and mobile phone addiction, pathways between these three constructs within a structural equation model have not yet been examined. Furthermore, there has been a dearth of studies exploring EFL writing anxiety, from which medical students in China as well as other non-English speaking countries are prone to suffer. The study was to assess EFL writing anxiety among Chinese medical students and to examine the relationships between EFL writing anxiety, self-esteem, and mobile phone addiction, with an aim to offer empirical evidence for effective preventive or intervention measures to alleviate EFL writing anxiety. Cross-sectional data were obtained from 1,238 medical students in China, with the administration of a self-administered questionnaire comprising the Second Language Writing Anxiety Inventory (SLWAI), the Rosenberg Self Esteem Scale (RSES) and the Mobile Phone Addiction Tendency Scale (MPATS). The results indicated that both self-esteem and mobile phone addiction exerted significant direct effects on EFL writing anxiety. Self-esteem also had a significant indirect effect on EFL writing anxiety via the mediating role of mobile phone addiction. The path coefficients of self-esteem on EFL writing anxiety were significantly reduced when mobile phone addiction was modeled as a mediator. Efforts to alleviate EFL writing anxiety among medical students may benefit from enhancing self-esteem and establishing a healthy relationship with mobile phones.

Neurodegeneration occurring in multiple sclerosis (MS) contributes to the progression of disability. It is therefore important to identify and neutralize the mechanisms that promote neurodegeneration in MS. Here, we report that oxidized phosphatidylcholines (OxPCs) found in MS lesions, previously identified as end-product markers of oxidative stress, are potent drivers of neurodegeneration. Cultured neurons and oligodendrocytes were killed by OxPCs, and this was ameliorated by microglia. After OxPC injection, mouse spinal cords developed focal demyelinating lesions with prominent axonal loss. The depletion of microglia that accumulated in OxPC lesions exacerbated neurodegeneration. Single-cell RNA sequencing of lesioned spinal cords identified unique subsets of TREM2high mouse microglia responding to OxPC deposition. TREM2 was detected in human MS lesions, and TREM2-/- mice exhibited worsened OxPC lesions. These results identify OxPCs as potent neurotoxins and suggest that enhancing microglia-mediated OxPC clearance via TREM2 could help prevent neurodegeneration in MS.

The current study looks to evaluate the effect of corn silk flavonoids on membranous nephropathy (MN). Polyamide resin (PR) can be used to enrich corn silk ethanol extract (CSEE) to obtain flavonoid-rich extract (PR-CSEE), the total flavonoid content (TFC) of which we found to be 57.4%. The results of scanning electron microscope, Fourier-transform infrared, and high-performance liquid chromatography analyses determined that PR-CSEE and CSEE have different structural characteristics, but that PR-CSEE has higher TFC. MN mice models were induced by cationic bovine serum albumin, and we found that PR-CSEE administration reduced urine protein levels markedly, while renal function, glomerular atrophy, inflammatory infiltration, and in-serum immunoglobulin G and complement 3 content were improved. Through LC-MS2 spectrometry analysis, we pinpointed the 12 major flavonoid active compounds in PR-CSEE. These findings suggest that PR-CSEE can act as a potential functional food material by which to improve MN.

This study was to provide a theoretical basis for effective treatment of myocardial ischemia-reperfusion injury (I/R injury) and explore the effect of cerium oxide (CeO2) nanoparticles on myocardial cell apoptosis induced by I/R injury. In this study, 50 healthy male Sprague Dawley (SD) rats were selected and divided into five groups according to the random table method: a sham operation group, an I/R group, a 1 - 10 nm CeO2 nanoparticle group (CeO2-1 group), a 10 - 25 nm CeO2 nanoparticle group (CeO2-2 group), and a 50 nm CeO2 nanoparticle group (CeO2-3 group). Rats in different groups were injected with phosphate buffer solution (PBS) and CeO2 nanoparticles with different diameters, respectively. The rat models of I/R injury were prepared to explore and analyze the superoxide dismutase (SOD) activity, malondialdehyde (MDA) content, glutathione peroxidase (GSH-Px) activity, and myocardial cell apoptosis of rats with I/R injury by CeO2 nanoparticles. The results showed that the cardiomyocyte necrosis, SOD activity, MDA content, GSH-Px activity, and apoptosis index of the three groups of rats injected with CeO2 nanoparticles were much better than those in the I/R group. The effects on SOD activity, MDA content, GSH-Px activity, and apoptosis index of cardiomyocytes in the CeO2-2 group were significantly better than those in the CeO2-1 and CeO2-3 groups, showing statistically great differences (P0.05); and effects on SOD activity, MDA content, and GSH-Px activity of cardiomyocytes in CeO2-1 group were better obviously than those in the CeO2-3 groups, showing statistically observable differences (P0.05). In addition, the difference between the CeO2-1 group and CeO2-3 on the apoptosis index of cardiomyocytes was not statistically remarkable (P0.05). It can be considered that the CeO2 nanoparticles can effectively alleviate the effects of myocardial I/R injury, showing reliable clinical significance.

Superpixel is an essential tool for computer vision. In practice, classic superpixel algorithms do not exhibit good boundary adherence with fewer superpixels, which will greatly hamper further analysis. To remedy the defect, a superpixel boundary optimization framework is proposed in this paper. There are three steps in the framework. Firstly, based on the proposed information measure function, the under-segmented superpixels generated by classic superpixel algorithms are screened out. Secondly, with the two invariant centroids method, these under-segmented superpixels are re-segmented to improve the accuracy in boundary adherence. Finally, smaller superpixels are merged to maintain the same number with initial superpixels. Quantitative evaluations on the BSDS500 exhibit that the performance of the classic superpixel algorithms is improved by employing the framework, especially on the condition of fewer superpixels.

New polyketide-derived oligophenalenone dimers, bacillisporins K and L (

Waveguide–plasmon polaritons sustained in metallic photonic crystal slabs show fascinating properties, such as narrow bandwidth and ultrafast dynamics crucial for biosensing, light emitting, and ultrafast switching. However, the patterning of metallic photonic crystals using electron beam lithography is challenging in terms of high efficiency, large area coverage, and cost control. This paper describes a controllable patterning technique for the fabrication of an Ag grating structure on an indium–tin oxide (ITO) slab that enables strong photon–plasmon interaction to obtain waveguide–plasmon polaritons. The Ag grating consisting of self-assembled silver nanoparticles (NPs) exhibits polarization-independent properties for the excitation of the hybrid waveguide–plasmon mode. The Ag NP grating can also be annealed at high temperature to form a continuous nanoline grating that supports the hybrid waveguide–plasmon mode only under transverse magnetic (TM) polarization. We tuned the morphology and the periodicity of the Ag grating through the concentration of silver salt and the photoresist template, respectively, to manipulate the strong coupling between the plasmon and the waveguide modes of different orders.

Neurodegeneration drives the progression of many neurological diseases. Inflammation and oxidative stress occurring in the CNS promote lipid peroxidation, leading to the generation of oxidized phospholipids such as oxidized phosphatidylcholines (OxPCs). OxPCs have been proposed as biomarkers of oxidative stress, where their detection in lesions in multiple sclerosis (MS), frontotemporal lobe dementia, spinal cord injury, and amyotrophic lateral sclerosis (ALS) implies that oxidative insult had occurred. However, recent findings highlight OxPCs as potent neurotoxic species requiring neutralization by microglia. Here, we summarize the science of OxPCs, including lessons from non-CNS diseases. We discuss the potential of OxPCs as common drivers of injury across neurological conditions and encourage investigations of OxPCs as novel neurotoxins.

The current study looks to evaluate the effect of corn silk flavonoids on membranous nephropathy (MN). Polyamide resin (PR) can be used to enrich corn silk ethanol extract (CSEE) to obtain flavonoid-rich extract (PR-CSEE), the total flavonoid content (TFC) of which we found to be 57.4%. The results of scanning electron microscope, Fourier-transform infrared, and high-performance liquid chromatography analyses determined that PR-CSEE and CSEE have different structural characteristics, but that PR-CSEE has higher TFC. MN mice models were induced by cationic bovine serum albumin, and we found that PR-CSEE administration reduced urine protein levels markedly, while renal function, glomerular atrophy, inflammatory infiltration, and in-serum immunoglobulin G and complement 3 content were improved. Through LC-MS

This study was conducted to evaluate the thyroid-disrupting effects of 2,2'-dipyridyl disulfide using Japanese flounder (Paralichthys olivaceus) as an animal model and to reveal the underlying mechanisms from the perspective of miRNA-mRNA interactions. The results indicated that 2,2'-dipyridyl disulfide exposure decelerated the metamorphic progress of P. olivaceus, suggesting its thyroid-disrupting property as an antagonist. Furthermore, radioimmunoassays, thyroid histological observation, real-time polymerase chain reaction, and mRNA sequencing showed that 2,2'-dipyridyl disulfide exposure exerted its thyroid-disrupting effects on larval and juvenile P. olivaceus by targeting multiple processes and pathways involved in the thyroid system, including peripheral metabolism of thyroid hormones, the thyroid hormone synthesis pathway, and the thyroid hormone/thyroid hormone receptor signaling pathway. In particular, global upregulation of the gene expression of three deiodinases caused decreases in thyroid hormone levels after 2,2'-dipyridyl disulfide exposure that are believed to be responsible for the inhibition of metamorphosis in P. olivaceus. Finally, miRNA sequencing suggested that several evolutionarily conserved miRNAs play important roles in the mechanism of 2,2'-dipyridyl disulfide-induced thyroid disruption. Specifically, overexpression of pny-miR-723a and pny-miR-216a resulted in upregulation of deiodinase 1 mRNA levels in the 2,2'-dipyridyl disulfide exposure group. This study provides the first evidence that 2,2'-dipyridyl disulfide has thyroid-disrupting properties and is also the first study remarking on the roles of miRNA-mRNA interactions in the action mechanisms of thyroid disruptors.

The aim of the study was to evaluate the neuroprotective function of sea cucumber ovum peptide-derived NDEELNK and explore the underlying molecular mechanisms. NDEELNK exerted the neuroprotective effect by improving the acetylcholine (ACh) level and reducing the acetylcholinesterase (AChE) activity in PC12 cells. By molecular docking, we confirmed that the NDEELNK backbone and AChE interacted through hydrophobic and hydrogen bonds in contact with the amino acid residues of the cavity wall. NDEELNK increased superoxide dismutase (SOD) activity and decreased reactive oxygen species (ROS) production, thereby reducing mitochondrial dysfunction and enhancing energy metabolism. Our results demonstrated that NDEELNK supplementation alleviated scopolamine-induced PC12 cell damage by improving the cholinergic system, increasing energy metabolism and upregulating the expression of phosphorylated protein kinase A (p-PKA), brain-derived neurotrophic factor (BNDF) and nerve growth factor (NGF) signaling proteins in in vitro experiments. These results demonstrated that the sea cucumber ovum peptide-derived NDEELNK might play a protective role in PC12 cells.

Anthropogenic land subsidence is an example of changes to the natural environment due to human activities and is one of the key factors in causing land degradation at a range of scales. Previous studies assessing land subsidence in the Valley of Mexico either focused on regional scale or short (noncontinuous) temporal scale. In this study, long‐term land subsidence (~15 years) is mapped in Mexico City (Mexico) using two interferometric synthetic aperture radar (InSAR) methods, namely, GEOS (Geoscience and Earth Observing Systems Group)‐Advance Time‐series Analysis and GEOS‐Small Baseline Subset. An inverse distance weighted‐based integration module and maximum likelihood regression‐based M estimator are introduced to further enhance these two methods. The land subsidence was continuously mapped using ENVISAT (2004–2007), ALOS‐1 (2007–2011), COSMO‐SkyMed (2011–2014), ALOS‐2 (2014–2018), and SENTINEL‐1 (2015–2017) data sets. A comparison between InSAR time‐series and GPS measurement shows that the subsidence rates are consistent over 2004–2018. The subsidence map over 15 years was generated finding a maximum subsidence over 4.5 m. By comparing our InSAR results with a land use map, we find that the subsidence centre in Mexico City is mostly located in the residential regions with the consumption of groundwater contributing considerably to the local subsidence rate. A total volume of 1.20 × 10⁸ m³ of the land in Ciudad Nezahualcoyotl subsided/degraded. A continuing subsidence process limits the potential land use causing serious land degradation. Our results may be used to assist disaster reduction plans.

Pine nut (Pinus koraiensis) peptide (PNP) powder possesses promising bioactivities. However, the powder may have the quality problem of becoming sticky and smelly. Therefore, the volatile compounds' fingerprint of PNP powder was established by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). The essential spoilage microorganisms were confirmed by 16S rDNA amplicon sequencing. The antioxidant activity, which presents PNP powder's quality, decreased during storage with the highest value of (1.88 ± 0.18) × 1014 at day 30. Fifty-nine significantly changed signals were detected; eight compounds were considered as volatile marker compounds. Besides, Firmicutes and Cyanobacteria were the essential spoilage microorganisms in PNP powder at the phylum level. Significantly, unidentified_Chloroplast, which belongs to Cyanobacteria, had a positive correlation with volatile marker compounds. The results proved that microorganisms indeed affect volatile compounds of PNP powder and induced off-flavor, including hexanal, which can be used as the detection indicator for the quality control of PNP powder. PRACTICAL APPLICATIONS: In the present study, we controlled the influence of moisture migration on PNP powder and investigated microorganisms' effects on volatile compounds of PNP powder. HS-GC-IMS could be used to establish fingerprints of volatile compounds in PNP powder. 16S rDNA amplicon sequencing method could be used to screen the dominant spoilage bacteria in PNP powder and established essential spoilage microorganisms of PNP powder. This work provides a reference for category identification of PNP powder, which was infected by spoilage bacteria or not, and stored at day 0 or 30 days. Hexanal can be considered as the volatile marker compound generated from microorganisms. It helps to realize the controllability of PNP powder storage and prolongs the shelf life of PNP powder.

Background and Aims: Aspirin leads to substantial benefits for the secondary prevention of cardiovascular disease (CVD). We aimed to cast more light on aspirin’s role for the primary prevention of CVD.Methods: Databases were searched for clinical trials comparing aspirin vs. no aspirin use in this meta-analysis. Efficacy and safety profiles were rigorously investigated. Trial sequential analysis (TSA) was used to determine the robustness of the results.Results: Fourteen studies with 163,840 participants were eligible (mean follow-up 6.2 y). Aspirin intake was found to be associated with 9, 13, and 12% reductions in the risk of cardiovascular events (CV events) (relative risk [RR]: 0.91, 95% confidence intervals [CI]: 0.87–0.96; risk difference (RD): 0.29%; absolute risk percentage (AR%): 7.61%; number needed to treat (NNT): 345), myocardial infarction (RR: 0.87, 95% CI: 0.77–0.97; RD: 0.21%; AR%: 11.11%; NNT: 488) and ischemic stroke (RR: 0.88, 95% CI: 0.80–0.96; RD: 0.21%; AR%: 16.14%; NNT: 476), respectively; aspirin intake was also associated with 40%, 30%, and 57% increases in the risk of major bleeding (RR: 1.40, 95% CI: 1.29–1.53; RD: 0.47%; AR%: 27.85; NNT: 214), intracranial bleeding (RR: 1.30, 95% CI: 1.11–1.52; RD: 0.10%; AR%: 22.99%; NNT: 1,000) and major gastrointestinal bleeding (RR: 1.57, 95% CI: 1.38–1.78; RD: 0.32%; AR%: 36.70%; NNT: 315), respectively. Further, populations with low doses of aspirin intake (≤100 mg), populations Conclusion: Aspirin intake was associated with a reduced risk of CV events and an increased incidence of bleeding profiles in primary prevention. It is necessary to identify individual’s CVD risk using clear examinations or assessments before aspirin intake, and truly realize individualized prescription.

As the underlying pathophysiology of progressive forms of multiple sclerosis (MS) remains unclear, current treatment strategies are inadequate. Progressive MS is associated with increased oxidative stress and neuronal damage in lesions along with an extensive representation of activated microglia/macrophages. To target these disease mechanisms, we tested the novel combination of generic medications, hydroxychloroquine (HCQ), and indapamide, in tissue culture and in mice. HCQ is an anti-malarial medication found to inhibit microglial activation and to ameliorate disease activity in experimental autoimmune encephalomyelitis. We are currently completing a phase II trial of HCQ in primary progressive MS (ClinicalTrials.gov Identifier: NCT02913157). Indapamide is an antihypertensive previously discovered in our laboratory drug screen to be an anti-oxidant. As these medications have a different spectrum of activities on disease mechanisms relevant to progressive MS, their use in combination may be more effective than either alone. We thus sought preclinical data for the effectiveness of this combination. In vitro, indapamide had robust hydroxyl scavenging activity, while HCQ and indapamide alone and in combination protected against iron-induced neuronal killing; TNF-α levels in activated microglia were reduced by either drug alone, without additional combination effects. In mice with a lysolecithin lesion that manifests demyelination and axonal loss in the spinal cord, the combination but not individual treatment of HCQ and indapamide reduced CD68(+) microglia/macrophage representation in lesions, attenuated axonal injury, and lowered levels of lipid peroxidation. Our study supports the combination of indapamide and HCQ as a new treatment strategy targeting multiple facets of progressive MS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13311-020-01002-5.

Background Chondroitin sulfate proteoglycans (CSPGs) are potent inhibitors of axonal regrowth and remyelination. More recently, they have also been highlighted as a modulator of macrophage infiltration into the central nervous system in experimental autoimmune encephalomyelitis, an inflammatory model of multiple sclerosis. Methods We interrogated results from single nucleotide polymorphisms (SNPs) lying in or close to genes regulating CSPG metabolism in the summary results from two publicly available systematic studies of multiple sclerosis (MS) genetics. A demyelinating injury model in the spinal cord of exostosin-like 2 deficient (EXTL2-/-) mice was used to investigate the effects of dysregulation of EXTL2 on remyelination. Cell cultures of bone marrow-derived macrophages and primary oligodendrocyte precursor cells and neurons were supplemented with purified CSPGs or conditioned media to assess potential mechanisms of action. Results The strongest evidence for genetic association was seen for SNPs mapping to the region containing the glycosyltransferase exostosin-like 2 (EXTL2), an enzyme that normally suppresses CSPG biosynthesis. Six of these SNPs showed genome-wide significant evidence for association in one of the studies with concordant and nominally significant effects in the second study. We then went on to show that a demyelinating injury to the spinal cord of EXTL2−/− mice resulted in excessive deposition of CSPGs in the lesion area. EXTL2−/− mice had exacerbated axonal damage and myelin disruption relative to wild-type mice, and increased representation of microglia/macrophages within lesions. In tissue culture, activated bone marrow-derived macrophages from EXTL2−/− mice overproduce tumor necrosis factor α (TNFα) and matrix metalloproteinases (MMPs). Conclusions These results emphasize CSPGs as a prominent modulator of neuroinflammation and they highlight CSPGs accumulating in lesions in promoting axonal injury.

Focal fibrocartilaginous dysplasia (FFCD) of the distal femur is a rare disorder that results in a varus or valgus of knee. Due to the small number of cases and unconfirmed natural history of the disease, treatment methods remain variable. This study aimed to determine a strategy to successfully manage distal femoral FFCD. Nine case of femoral FFCD treated in our department between 2008 and 2018, together with 22 cases from literature, were retrospectively reviewed. Tibiofemoral anatomical axis angle (TFA) was used to evaluate and follow the deformities. Treatment methods and outcome were analyzed. Five methods were used to manage the disease: osteotomy with tether release in 14 cases with mean TFA of 29°; simple tether release in eight cases with mean TFA of 31°; guide growth without tether release in 3 case with mean TFA of 27°; guide growth with tether release in 3 case with mean TFA of 27°; and observation in three cases with mean TFA of 23°.Deformity was resolved in all 31 patients. The analysis of the 31 cases in the literature and our experience suggests that femoral FFCD can be successfully managed by simple tether release and curettage. Osteotomy can be avoided. In case of mild deformity (TFA < 25°), it is reasonable to follow-up till 2-3 years of age; if no progress occurs, spontaneous resolution can be expected.

The SARS-CoV-2 epidemic starting in Wuhan in December, 2019 has spread rapidly throughout the nation. The control measures to contain the epidemic also produced influences on the transport and treatment process of patients with acute myocardial infarction (AMI), and adjustments in the management of the patients need to be made at this particular time. AMI is characterized by an acute onset with potentially fatal consequence, a short optimal treatment window, and frequent complications including respiratory infections and respiratory and circulatory failure, for which active on-site treatment is essential. To standardize the management and facilitate the diagnosis and treatment, we formulated the guidelines for the procedures and strategies for the diagnosis and treatment of AMI, which highlight 5 Key Principles, namely Nearby treatment, Safety protection, Priority of thrombolysis, Transport to designated hospitals, and Remote consultation. For AMI patients, different treatment strategies are selected based on the screening results of SARS-CoV-2, the time window of STEMI onset, and the vital signs of the patients. During this special period, the cardiologists, including the interventional physicians, should be fully aware of the indications and contraindications of thrombolysis. In the transport and treatment of AMI patients, the physicians should strictly observe the indications for patient transport with appropriate protective measurements of the medical staff.

ObjectiveThe detailed associations between type 2 diabetes (T2D) and total stroke and magnesium intake as well as the dose–response trend should be updated in a timely manner.DesignSystematic review and meta-analyses.Data sourcesPubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov were rigorously searched from inception to 15 March 2019.Eligibility criteriaProspective cohort studies investigating these two diseases were included.Data synthesisRelative risk (RR) and 95% CI in random effects models as well as absolute risk (AR) were pooled to calculate the risk of T2D and stroke. Methodological quality was assessed by the Newcastle-Ottawa Scale.ResultsForty-one studies involving 53 cohorts were included. The magnitude of the risk was significantly reduced by 22% for T2D (RR 0.78 (95% CI 0.75 to 0.81); p2body mass index and those with ≥12-year follow-up; the reduced risk in Asians was not as notable as that in North American and European populations.ConclusionsMagnesium intake has significantly inverse associations with T2D and total stroke in a dose-dependent manner. Feasible magnesium-rich dietary patterns may be highly beneficial for specific populations and could be highlighted in the primary T2D and total stroke prevention strategies disseminated to the public.PROSPERO registration numberCRD42018092690.

Microglia respond to white matter injury with different populations that prevent macrophage dispersion into spared tissue., Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response to injury; however, the similarities between these cells make it challenging to distinguish their relative contributions. We genetically labeled microglia and CNS-associated macrophages to distinguish them from infiltrating macrophages. Using single-cell RNA sequencing, we describe multiple microglia activation states, one of which was enriched for interferon associated signaling. Although blood-derived macrophages acutely infiltrated the demyelinated lesion, microglia progressively monopolized the lesion environment where they surrounded infiltrating macrophages. In the microglia-devoid sciatic nerve, the infiltrating macrophage response was sustained. In the CNS, the preferential proliferation of microglia and sparse microglia death contributed to microglia dominating the lesion. Microglia ablation reversed the spatial restriction of macrophages with the demyelinated spinal cord, highlighting an unrealized macrophages-microglia interaction. The restriction of peripheral inflammation by microglia may be a previously unidentified mechanism by which the CNS maintains its “immune privileged” status.

New polyketide-derived oligophenalenone dimers, bacillisporins K and L (1 and 2) and xanthoradone dimer rugulosin D (3), together with four known compounds, bacillisporin B (4), macrosporusone D (5), rugulosin A and penicillide (6 and 7), were isolated from the marine-derived fungus Talaromyces sp. BTBU20213036. Their structures were determined by detailed analysis of HRESIMS, 1D and 2D NMR data, and the absolute configurations were determined on the basis of calculated and experimental electronic circular dichroism (ECD). The antibacterial and antifungal activities of these compounds were tested against Gram-positive—Staphylococcus aureus, Gram-negative—Escherichia coli, and fungal strain—Candida albicans. These compounds showed potential inhibitory effects against S. aureus with minimum inhibitory concentrations ranging from 0.195 to 100 µg/mL.

The flavor fingerprint of sea cucumbers was developed and volatile compounds were investigated by HS-GC-IMS. A total of 73 typical target compounds were identified. The differences of flavor compounds in sea cucumbers from different seasonings soaking samples areas were observed. After soaking, the concentration of compounds such as 1-octen-3-one and 3-methyl-2-butanol in sea cucumbers were decreased, while the concentration of representative flavor compounds in seasonings such as β-ocimene, linalool and furaneol were increased. Subsequently, PCA was performed based on the signal intensity of the identified flavor compounds, and the results clearly showed that the sea cucumbers without seasonings group and seasonings-soaked sea cucumbers samples in a relatively independent space would be well distinguished. The results showed that the flavor fingerprint of sea cucumbers was established by HS-GC-IMS and PCA based on the identified volatile compounds.

Hyperspectral unmixing (HU) is a research hotspot of hyperspectral remote sensing technology. As a classical HU method, the nonnegative matrix factorization (NMF) unmixing method can decompose an observed hyperspectral data matrix into the product of two nonnegative matrices, i.e., endmember and abundance matrices. Because the objective function of NMF is the traditional least-squares function, NMF is sensitive to noise. In order to improve the robustness of NMF, this paper proposes a maximum likelihood estimation (MLE) based NMF model (MLENMF) for unmixing of hyperspectral images (HSIs), which substitutes the least-squares objective function in traditional NMF by a robust MLE-based loss function. Experimental results on a simulated and two widely used real hyperspectral data sets demonstrate the superiority of our MLENMF over existing NMF methods.

Semicarbazide (SMC) is a carcinogenic and genotoxic substance that has been found in aquatic systems. SMC may also cause thyroid follicular epithelial cell injury in rats, but the thyroid-disrupting properties of SMC and its potential mechanisms remain unclear. In this study, we exposed fertilized eggs of Japanese flounder (Paralichthys olivaceus) to 1, 10, 100, and 1000 μg/L SMC for 55 d to assess the impact of SMC exposure on the thyroid system. The number of larvae in each metamorphic stage was counted, the concentrations of whole-body thyroid hormones (THs) 3,5,3′-triiodothyronine (T3) and thyroxine (T4) were measured, and the transcription levels of genes involved in the hypothalamic-pituitary-thyroid (HPT) axis and gamma-aminobutyric acid (GABA) synthesis were quantified. The results showed that 10 μg/L SMC significantly increased whole-body T3 levels, and 100 and 1000 μg/L SMC markedly enhanced whole-body T4 and T3 levels. Furthermore, 100 μg/L SMC exposure shortened the time it took for flounder larvae to complete metamorphosis by 2 d as compared to the control group. Thus, this study demonstrated that SMC exerted thyroid-disrupting effects on Japanese flounder. SMC-mediated stimulation of TH levels was primarily related to transcriptional alterations of pituitary-derived thyroid stimulating hormone β-subunit (tshβ) and hepatic deiodinase (id). In the 10 and 100 μg/L SMC exposure groups, the increased TH levels may have resulted from inhibition of TH metabolism caused by down-regulation of id3 mRNA expression, while at 1000 μg/L SMC-exposed group, up-regulation of tshβ and id1 transcripts was expected to enhance the synthesis of T4 and the conversion of T4 to T3 and, consequently, result in higher T4 and T3 levels. In addition, 1000 μg/L SMC-induced down-regulation in glutamic acid decarboxylase gad65 and gad67 transcription may have also contributed to the increased TH levels. The thyroid-disrupting effects of 10 and 100 μg/L SMC indicated that environmentally relevant concentrations of SMC posed potential environmental risks to aquatic organisms. Overall, our results demonstrated for the first time that SMC exhibited thyroid-disrupting properties by affecting the HPT axis and GABA synthesis, providing theoretical support for environmental risk assessment.

Alveolar macrophages (AMs) are CD44 expressing cells that reside in the alveolar space where they maintain lung homeostasis by serving critical roles in immunosurveillance and lipid surfactant catabolism. AMs lacking CD44 are unable to bind the glycosaminoglycan, hyaluronan, which compromises their survival and leads to reduced numbers of AMs in the lung. Using RNA sequencing, lipidomics and multiparameter flow cytometry, we demonstrate that CD44-/- mice have impaired AM lipid homeostasis and increased surfactant lipids in the lung. CD44-/- AMs had increased expression of CD36, a lipid scavenger receptor, as well as increased intracellular lipid droplets, giving them a foamy appearance. RNA sequencing revealed the differential expression of genes associated with lipid efflux and metabolism in CD44-/- AMs. Lipidomic analysis showed increased lipids in both the supernatant and cell pellet extracted from the bronchoalveolar lavage of CD44-/- mice. Phosphatidylcholine species, cholesterol, oxidized phospholipids and levels of reactive oxygen species (ROS) were increased in CD44-/- AMs. Oxidized phospholipids were more cytotoxic to CD44-/- AMs and induced greater lung inflammation in CD44-/- mice. Reconstitution of CD44+/+ mice with CD44-/- bone marrow as well as adoptive transfer of CD44-/- AMs into CD44+/+ mice showed that lipid accumulation in CD44-/- AMs occurred irrespective of the lung environment, suggesting a cell intrinsic defect. Administration of colony stimulating factor 2 (CSF-2), a critical factor in AM development and maintenance, increased AM numbers in CD44-/- mice and decreased phosphatidylcholine levels in the bronchoalveolar lavage, but was unable to decrease intracellular lipid accumulation in CD44-/- AMs. Peroxisome proliferator-activated receptor gamma (PPARγ), downstream of CSF-2 signaling and a regulator of lipid metabolism, was reduced in the nucleus of CD44-/- AMs, and PPARγ inhibition in normal AMs increased their lipid droplets. Thus, CD44 deficiency causes defects in AMs that lead to abnormal lipid accumulation and oxidation, which exacerbates oxidized lipid-induced lung inflammation. Collectively, these findings implicate CD44 as a regulator of lung homeostasis and inflammation.

Background CYP2C19*17 (rs12248560) is a functional single nucleotide polymorphism (SNP) in the CYP2C19 gene. It has been shown that CYP2C19*17 is associated with the clinical outcome of some drugs metabolized by CYP2C19 and a decreased risk of some diseases. The aim of this study was to develop a reliable and simple method to detect this polymorphism. Methods Tetra‐primer amplification refractory mutation system‐polymerase chain reaction (T‐ARMS‐PCR) was used to detect the CYP2C19*17 polymorphism. A total of 93 samples were screened by this method, and the results of T‐ARMS‐PCR were validated by DNA sequencing. Results There were 91 samples with the CC genotype (97.8%) and two samples with the CT genotype (2.2%). The frequency of the C allele was 98.9%, and the frequency of the T allele was 1.1%. The DNA sequencing results were completely concordant with the T‐ARMS‐PCR results. Conclusion T‐ARMS‐PCR can detect the CYP2C19*17 polymorphism with high accuracy, low costs, and a simple process.

Children presenting with partial physeal arrest and significant remaining growth may benefit from physeal bar resection, although the operation is a technique demanding procedure. This study evaluates the treatment of post-traumatic pediatric ankle varus deformity using physeal bar resection and hemi-epiphysiodesis with the assistance of two operative methods. Forty-five patients presenting with a distal tibial medial physeal bridge as well as ankle varus deformity following traumatic ankle physeal injury between 2009 and 2017 were followed. These patients were treated with physeal bar resection and hemi-epiphysiodesis, with the assistance of either fluoroscopy (10 cases) or intraoperative three-dimensional navigation (35 cases). Of the 45 cases, the median age was 9.0 years (range: 3-14 years) with 28 male and 17 female patients. The median of pre-operation ankle varus angle was 20 degrees (IQR 15-25) and 5 degrees (IQR 0-20) at the time of final follow up, representing a statistically significant difference (P0.05). No differences were observed with regards to age, gender, and surgical history between effective group and ineffective group (P0.05). The median of pre-operative ankle varus angles of the navigation and fluoroscopy groups were both 20 degrees (P0.05). The median correction angle of the navigation and fluoroscopy groups was 10 and 15 degrees, respectively (P0.05). Our results indicate that physeal bar resection and hemiepiphysiodesis are effective treatments for correcting ankle varus deformity due to traumatic medial physeal arrest of the distal tibia. We observe no difference in outcome between fluoroscopy group and three-dimensional navigation group during the procedures.

A rapid and sensitive measurement technique was used to investigate the mechanism of aroma compounds changes in SCPPs under the storage conditions with hygroscopicity and no-microorganism (HNM), nonhygroscopicity and no-microorganism (NHNM) and hygroscopicity and microorganism (HM) by HS-GC-IMS. The types and signal of aroma compounds increased obviously at the 5th day under the storage condition (HNM and HM). The signal of majority of aroma compounds decreased gradually since the 5th day. However, during the storage of SCPPs for 15 days, the total signals of aldehydes, ketones and alcohols gradually increased and reached a maximum. Thereinto, the saturated aldehydes such as hexanal had been produced as an off-flavor. These off-flavor compounds principally including aldehydes and ketones could be generated through Maillard reaction, while alcohols could be generated by microbial fermentation. The study discovered moisture adsorption and microorganism during storage could affect aroma compounds of SCPPs and the effect of moisture absorption was greater than microorganisms.

The effect of pulsed electric field (PEF) treatment on the intracellular antioxidant and apoptotic activity of the peptide Lys-Asp-His-Cys-His (KDHCH) was examined using model HepG2 cells. First, PEF treatment conditions specific for the antioxidant peptide were optimized, and it was found that PEF treatment could enhance DPPH, ABTS and hydroxyl radical scavenging capacity of KDHCH. Second, KDHCH subjected to PEF treatment at 1800 Hz and 15 kV/cm was investigated using various intracellular antioxidant assays. PEF treatment decreased the EC50 value and increased the protective ability of oxidative stress inhibition and reactive oxygen species (ROS) scavenging activity of KDHCH. Furthermore, catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and glutathione reductase (GR) activities of KDHCH-pre-treated HepG2 cells increased significantly compared with those of the H2O2 damaged group, whereas lactate dehydrogenase (LDH) and malonaldehyde (MDA) content were decreased. PEF-treated KDHCH exhibited an increased capacity to maintain the stability of mitochondrial membrane potential (MMP) and reduced the level of caspase-3. These results indicate that PEF treatment can enhance the intracellular antioxidant activity of KDHCH, which can inhibit the effect of H2O2 oxidation on HepG2 cells by inhibiting the accumulation of intracellular ROS, regulating antioxidant related enzymes, and blocking the apoptotic mitochondrial pathways activated by ROS.

The present study was to analyze the water dynamics of Tricholoma matsutake Singer during hot air drying by low-field nuclear magnetic resonance (LF-NMR) and magnetic resonance imaging (MRI), and to investigate the volatile compounds in the pileus, upper stipe and lower stipe of fresh and dried Tricholoma matsutake Singer by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and headspace solid-phase microextraction-gas chromatography–mass spectrometry (HS-SPME-GC–MS). Fresh samples were dried at 60 °C for 12 h. With the T2i relaxation times decreasing, the water migrated from the inner toward the periphery and then expelled during drying. The characteristic volatiles fingerprints of different parts of fresh and dried samples were established by HS-GC-IMS. The significant differences in volatile compounds were observed among different parts of the fresh sample and C8 compounds (70%–97%) were the principal components. After drying, the concentration of C8 compounds dramatically decreased and some volatile compounds (hexanal, heptanal, 2(5H)-furanone, acetophenone, nonanal, benzeneacetaldehyde) were formed. Thus, hot air treatment affected the volatile compounds in Tricholoma matsutake Singer.

The formation pattern of off-flavor compounds induced by water migration in sea cucumber peptide powders (SCPPs) stored at 25 °C and 75% RH for 24 h and 80 days were investigated. Water migration characteristic of SCPPs was monitored by LF-NMR. The effect of water migration on structure and morphology were analyzed by SEM, CD, and FTIR, respectively. The antioxidant activity of SCPPs was detected by EPR. Volatiles generated from SCPPs were detected by P&T-GC-MS. The antioxidant activity of SCPPs declined and structure exhibited abnormalities during the storage. After 24 h of storage, kinds of aldehydes decreased and the content of alcohols increased obviously. After 80 days, (Z)-3,5-dimethyl-2-(1-propenyl)-pyrazine and 1,2-benzenedicarboxylic acid-bis(2-methylpropyl) ester were identified as the characteristic off-flavor. These off-flavor compounds were probably formed through Maillard reaction. esterification, and microbial metabolism. This study can provide a basis for further exploration of the off-flavor formation mechanism.