Solvent-regulated self-assembled carbon nitride for photocatalytic reduction of U(VI) in water.

Manufacturing high-performance and reusable materials from radioactive uranium-containing wastewater remains a significant challenge. Herein, a supramolecular self-assembly strategy was proposed, using melamine and cyanuric acid as precursors and using intermolecular hydrogen bond force to form carbon nitride (CN-D) in different solvents through a single thermal polymerization strategy. Supramolecular self-assembly method is a promising strategy to synthesize a novel carbon nitride with molecular regulatory properties. In addition, 98% of U(VI) in wastewater can be removed by using CN-D for 60 min under visible light. After five cycles of recycling, more than 95% of U(VI) can still be reduced, indicating that it has good recyclability and reusability. This study not only provides an efficient photocatalytic method of uranium reduction, but also provides a new method for self-assembly synthesis.

Protectin Conjugates in Tissue Regeneration 1 Inhibits Macrophage Pyroptosis by Restricting NLRP3 Inflammasome Assembly to Mitigate Sepsis via the cAMP-PKA Pathway.

Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel anti-inflammatory and proresolving lipid mediator biosynthesized from docosahexaenoic acid. Excessive activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome and consequent pyroptosis are involved in diverse inflammatory diseases. However, how PCTR1 affects NLRP3 inflammasome activation and pyroptosis are still unclear. Here, we demonstrated that PCTR1 inhibited NLRP3 inflammasome activation and pyroptosis. These results show that PCTR1 dose-dependently inhibited gasdermin D cleavage in lipopolysaccharide (LPS)-primed murine primary macrophages upon nigericin stimulation. Additionally, PCTR1 treatment after LPS priming inhibited caspase-1 activation and subsequent mature interleukin-1ß release independent of the nuclear factor-kappa B pathway. PCTR1 exerted its inhibitory effects by blocking NLRP3-apoptosis-associated speck-like protein containing a CARD (ASC) interaction and ASC oligomerization, thereby restricting NLRP3 inflammasome assembly. However, the inhibitory effect of PCTR1 could be reversed by KH7 and H89, which are the inhibitors of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway. Moreover, PCTR1 treatment alleviated lung tissue damage and improved mouse survival in LPS-induced sepsis. Our study unveils the molecular mechanism of negative regulation of NLRP3 inflammasome activation and pyroptosis by a novel lipid mediator and suggests that PCTR1 may serve as a potential treatment option for NLRP3-inflammasome driven diseases.

Identification of genetic variants associated with diabetic kidney disease in multiple Korean cohorts via a genome-wide association study mega-analysis.

BACKGROUND: The pathogenesis of diabetic kidney disease (DKD) is complex, involving metabolic and hemodynamic factors. Although DKD has been established as a heritable disorder and several genetic studies have been conducted, the identification of unique genetic variants for DKD is limited by its multiplex classification based on the phenotypes of diabetes mellitus (DM) and chronic kidney disease (CKD). Thus, we aimed to identify the genetic variants related to DKD that differentiate it from type 2 DM and CKD. METHODS: We conducted a large-scale genome-wide association study mega-analysis, combining Korean multi-cohorts using multinomial logistic regression. A total of 33,879 patients were classified into four groups-normal, DM without CKD, CKD without DM, and DKD-and were further analyzed to identify novel single-nucleotide polymorphisms (SNPs) associated with DKD. Additionally, fine-mapping analysis was conducted to investigate whether the variants of interest contribute to a trait. Conditional analyses adjusting for the effect of type 1 DM (T1D)-associated HLA variants were also performed to remove confounding factors of genetic association with T1D. Moreover, analysis of expression quantitative trait loci (eQTL) was performed using the Genotype-Tissue Expression project. Differentially expressed genes (DEGs) were analyzed using the Gene Expression Omnibus database (GSE30529). The significant eQTL DEGs were used to explore the predicted interaction networks using search tools for the retrieval of interacting genes and proteins. RESULTS: We identified three novel SNPs [rs3128852 (P = 8.21×10-25), rs117744700 (P = 8.28×10-10), and rs28366355 (P = 2.04×10-8)] associated with DKD. Moreover, the fine-mapping study validated the causal relationship between rs3128852 and DKD. rs3128852 is an eQTL for TRIM27 in whole blood tissues and HLA-A in adipose-subcutaneous tissues. rs28366355 is an eQTL for HLA-group genes present in most tissues. CONCLUSIONS: We successfully identified SNPs (rs3128852, rs117744700, and rs28366355) associated with DKD and verified the causal association between rs3128852 and DKD. According to the in silico analysis, TRIM27 and HLA-A can define DKD pathophysiology and are associated with immune response and autophagy. However, further research is necessary to understand the mechanism of immunity and autophagy in the pathophysiology of DKD and to prevent and treat DKD.

MIL-100(Fe)/g-C3N4 composites with enhanced photocatalytic activity for UO22+ reduction under visible light.

As a clean energy source, nuclear energy can gradually replace traditional fossil energy sources, and is an important means to achieve the "double carbon goal". Uranium-containing wastewater is inevitable in the development of nuclear energy. The composites MIL/CNx of MOF material MIL-100(Fe) and carbon nitride (CN) were obtained by a simple solvo-thermal method using iron nitrate, homophthalic acid and CN. The material MIL-100(Fe) with high specific surface area was compounded with CN to increase the in-plane adsorption sites, which could adsorb 30% of uranium in solution during the dark reaction. The close interfacial contact of the two materials effectively inhibited the complexation of photo-generated electrons and holes and promotes electron migration. These two synergistic effects improved their overall photocatalytic reduction capacity, which could reduce 97% of UO22+ in solution in 20 min. The UO22+ removal efficiency of MIL/CN0.1 was 2.3 and 1.6 times higher than that of CN and MIL-100(Fe), respectively. In addition, MIL/CN0.1 was stable in reducing uranium during the five cycles of the experiment.

Soyasaponin I alleviates hypertensive intracerebral hemorrhage by inhibiting the renin-angiotensin-aldosterone system.

BACKGROUND: Hypertensive intracerebral hemorrhage (HICH) is a life-threatening disease and lacks effective treatments. Previous studies have confirmed that metabolic profiles altered after ischemic stroke, but how brain metabolism changes after HICH was unclear. This study aimed to explore the metabolic profiles after HICH and the therapeutic effects of soyasaponin I on HICH. METHODS: HICH model was established first. Hematoxylin and eosin staining was used to estimate the pathological changes after HICH. Western blot and Evans blue extravasation assay were applied to determine the integrity of the blood-brain barrier (BBB). Enzyme-linked immunosorbent assay was used to detect the activation of the renin-angiotensin-aldosterone system (RAAS). Next, liquid chromatography-mass spectrometry-untargeted metabolomics was utilized to analyze the metabolic profiles of brain tissues after HICH. Finally, soyasaponin I was administered to HICH rats, and the severity of HICH and activation of the RAAS were further assessed. RESULTS: We successfully constructed HICH model. HICH significantly impaired BBB integrity and activated RAAS. HICH increased PE(14:0/24:1(15Z)), arachidonoyl serinol, PS(18:0/22:6(4Z, 7Z, 10Z, 13Z, 16Z, and 19Z)), PS(20:1(11Z)/20:5(5Z, 8Z, 11Z, 14Z, and 17Z)), glucose 1-phosphate, etc., in the brain, whereas decreased creatine, tripamide, D-N-(carboxyacetyl)alanine, N-acetylaspartate, N-acetylaspartylglutamic acid, and so on in the hemorrhagic hemisphere. Cerebral soyasaponin I was found to be downregulated after HICH and supplementation of soyasaponin I inactivated the RAAS and alleviated HICH. CONCLUSION: The metabolic profiles of the brains changed after HICH. Soyasaponin I alleviated HICH via inhibiting the RAAS and may serve as an effective drug for the treatment of HICH in the future.

From cis-Lobeline to trans-Lobeline: Study on the Pharmacodynamics and Isomerization Factors.

Lobeline is an alkaloid derived from the leaves of an Indian tobacco plant (Lobelia inflata), which has been prepared by chemical synthesis. It is classified as a partial nicotinic agonist and has a long history of therapeutic usage ranging from emetic and respiratory stimulant to tobacco smoking cessation agent. The presence of both cis and trans isomers in lobeline is well known, and many studies on the relationship between the structure and pharmacological activity of lobeline and its analogs have been reported. However, it is a remarkable fact that no studies have reported the differences in pharmacological activities between the two isomers. In this article, we found that different degrees of isomerization of lobeline injection have significant differences in respiratory excitatory effects in pentobarbital sodium anesthetized rats. Compared with cis-lobeline injections, the respiratory excitatory effect was significantly reduced by 50.2% after administration of injections which contained 36.9% trans-lobeline. The study on the influencing factors of isomerization between two isomers shown that this isomerization was a one-way isomerism and only converted from cis to trans, where temperature was the catalytic factor and pH was the key factor. This study reports a new discovery. Despite the widespread use of ventilators, first-aid medicines such as nikethamide and lobeline has retired to second line, but as a nonselective antagonist with high affinity for a4b2 and a3b2 nicotinic acetylcholine receptors (nAChRs). In recent years, lobeline has shown great promise as a therapeutic drug for mental addiction and nervous system disorders, such as depression, Alzheimer disease and Parkinson disease. Therefore, we suggest that the differences between two isomers should be concerned in subsequent research papers and applications.

Endogenous Ca2+ release was involved in 50-Hz MF-induced proliferation via Akt-SK1 signal cascade in human amniotic epithelial cells.

The mechanism underlying the biological effects caused by an extremely low-frequency electromagnetic field (ELF-EMF) is still unclear. Previously, we found that L-type calcium channel and sphingosine kinase 1 (SK1) were involved in 50-Hz MF exposure-induced cell proliferation. In the present study, the role of intracellular Ca2+ and signal molecules related to SK1 in cell proliferation induced by 50-Hz MF was investigated in human amniotic epithelial (FL) cells. Results showed that the intracellular Ca2+ chelator, BAPTA, could completely inhibit 50-Hz MF-induced cell proliferation, whereas NIF, the inhibitor of L-type calcium channel, only partly blocked it. When cells were cultured in calcium-free medium, MF exposure also increased intracellular Ca2+, activated SK1 and promoted cell proliferation although all of those increasing levels were lower than those in complete medium. Moreover, MF-activated SK1 could be completely inhibited by BAPTA, and MF-induced cell proliferation was abolished by SKI II, the specific inhibitor of SK1. Additionally, a 50-Hz MF exposure did not affect the activation of ERK and PKCα under the condition of calcium-free medium, but activated the Akt, which could be precluded entirely by BAPTA, but not be inhibited by NIF. Treatment of FL cells with LY294002, the inhibitor of Akt, could delete the MF-induced SK1 activation under the condition of calcium-free medium. Based on the data from the present experiment, it is concluded that endogenous Ca2+ release was involved in 50-Hz MF-induced cell proliferation via Akt-SK1 signal cascade.

Comparison of conjunctival vascularity changes using optical coherence tomography angiography after trabeculectomy and phacotrabeculectomy.

PURPOSE: To compare bleb vascularity changes using optical coherence tomography angiography (OCT-A) between mitomycin-C (MMC)-augmented trabeculectomy and phacotrabeculectomy and to determine whether bleb vascularity measurements during preoperative and early postoperative periods could act as surrogate parameters to predict surgical outcomes. METHODS: We retrospectively reviewed data for 72 eyes from 72 glaucoma patients who underwent MMC-augmented trabeculectomy with/without cataract surgery. Bleb area scans were obtained using OCT-A during the preoperative period; 1, 2, 4, and 6 weeks postoperatively; and 2, 4, and 6 months postoperatively. For conjunctival vascularity analysis, a semi-automated program was used to calculate color and brightness densities of the selected area. RESULTS: Color and brightness densities were decreased in the trabeculectomy group during all periods but not in the phacotrabeculectomy group at 4 and 6 weeks, as well as 2, 4, and 6 months postoperatively. Color and brightness densities were significantly higher in the phacotrabeculectomy group than in the trabeculectomy group after 6 weeks and 2, 4, and 6 months postoperatively. A Kaplan-Meier survival graph indicated that intraocular pressure differed according to glaucoma type but not surgery type. Logistic regression analysis revealed that brightness density 1 week postoperatively was correlated with reoperation. CONCLUSIONS: Changes in conjunctival vascularity density measured by OCT-A differed according to the surgical method. Following trabeculectomy with MMC, brightness density 1 week postoperatively may be a predictive index for surgical outcomes.

Pharmacogenetic role of dopamine transporter (SLC6A3) variation on response to disulfiram treatment for cocaine addiction.

BACKGROUND AND OBJECTIVES: Disulfiram has been beneficial in treating cocaine addiction in several studies. Patients with two SLC6A3 (DAT1) rs28363170 10-repeat alleles who have with genetically high dopamine transporter (DAT) levels may benefit from increased dopamine levels resulting from disulfiram treatment. METHODS: After stabilization for 2 weeks on methadone, 70 cocaine and opioid codependent patients were randomized into disulfiram and placebo groups for 12 weeks of treatment. We genotyped the SLC6A3 (DAT1) 40 bp 3'-untranslated region variable number tandem repeat variant and evaluated its role in moderating disulfiram efficacy for cocaine dependence. RESULTS: Among the 10,10-repeat genotype group, cocaine-positive urines dropped from 78% to 48% and from 80% to 75% among the 9-repeat carrier group in the disulfiram group (P = 0.0001, with an effect size of 0.09). No difference was observed in cocaine-positive urines in the placebo group between the 10,10-repeat genotype and the 9-allele carrier patients. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: We found that patients with genetically higher DAT levels had better treatment outcomes with disulfiram pharmacotherapy of cocaine dependence than those with lower DAT levels. (Am J Addict 2019;28:311-317).

Sex differences in the prevalence of metabolic syndrome and its components in hypopituitary patients: comparison with an age- and sex-matched nationwide control group.

PURPOSE: Hypopituitary patients have a reduced life expectancy owing to cardiovascular events. We investigated the prevalence of metabolic syndrome in hypopituitary patients for a follow-up period of at least 1 year in comparison with an age- and sex-matched nationwide control group. METHODS: A total of 515 patients with hypopituitarism who visited Seoul National University Hospital between January 2000 and December 2010 were included. Data for an age- and sex-matched control group were obtained from the Korean National Health and Nutrition Examination Surveys (KNHANES) (n = 1545). Metabolic syndrome was defined according to the modified National Cholesterol Education Program (NCEP-ATPIII). RESULTS: The prevalence of metabolic syndrome did not differ significantly between the hypopituitary and control groups for men (34.9 versus 30.3 %), but the risk of metabolic syndrome was higher in hypopituitary women than in controls (39.8 versus 28.5 %). In both sexes, the risks of central obesity and dyslipidemia were higher in the hypopituitary group than in the control group. Men had lower risks of hypertension and hyperglycemia in the hypopituitary group, which attenuated the risk of metabolic syndrome. Age greater than 40 years and obesity (BMI ≥25 kg/m2) contributed to a higher risk of metabolic syndrome. CONCLUSIONS: The metabolic syndrome prevalence was higher in the hypopituitry group than in the control group in Korean women, and this was attributed to an increased risk of central obesity and dyslipidemia. Accordingly, early intervention to reduce metabolic syndrome needed in hypopituitary patients, i.e. women.

Myosin light chain kinase (MLCK) regulates cell migration in a myosin regulatory light chain phosphorylation-independent mechanism.

Myosin light chain kinase (MLCK) has long been implicated in the myosin phosphorylation and force generation required for cell migration. Here, we surprisingly found that the deletion of MLCK resulted in fast cell migration, enhanced protrusion formation, and no alteration of myosin light chain phosphorylation. The mutant cells showed reduced membrane tether force and fewer membrane F-actin filaments. This phenotype was rescued by either kinase-dead MLCK or five-DFRXXL motif, a MLCK fragment with potent F-actin-binding activity. Pull-down and co-immunoprecipitation assays showed that the absence of MLCK led to attenuated formation of transmembrane complexes, including myosin II, integrins and fibronectin. We suggest that MLCK is not required for myosin phosphorylation in a migrating cell. A critical role of MLCK in cell migration involves regulating the cell membrane tension and protrusion necessary for migration, thereby stabilizing the membrane skeleton through F-actin-binding activity. This finding sheds light on a novel regulatory mechanism of protrusion during cell migration.

Two-stage sparse multi-objective evolutionary algorithm for channel selection optimization in BCIs.

Background: Channel selection has become the pivotal issue affecting the widespread application of non-invasive brain-computer interface systems in the real world. However, constructing suitable multi-objective problem models alongside effective search strategies stands out as a critical factor that impacts the performance of multi-objective channel selection algorithms. This paper presents a two-stage sparse multi-objective evolutionary algorithm (TS-MOEA) to address channel selection problems in brain-computer interface systems. Methods: In TS-MOEA, a two-stage framework, which consists of the early and late stages, is adopted to prevent the algorithm from stagnating. Furthermore, The two stages concentrate on different multi-objective problem models, thereby balancing convergence and population diversity in TS-MOEA. Inspired by the sparsity of the correlation matrix of channels, a sparse initialization operator, which uses a domain-knowledge-based score assignment strategy for decision variables, is introduced to generate the initial population. Moreover, a Score-based mutation operator is utilized to enhance the search efficiency of TS-MOEA. Results: The performance of TS-MOEA and five other state-of-the-art multi-objective algorithms has been evaluated using a 62-channel EEG-based brain-computer interface system for fatigue detection tasks, and the results demonstrated the effectiveness of TS-MOEA. Conclusion: The proposed two-stage framework can help TS-MOEA escape stagnation and facilitate a balance between diversity and convergence. Integrating the sparsity of the correlation matrix of channels and the problem-domain knowledge can effectively reduce the computational complexity of TS-MOEA while enhancing its optimization efficiency.

Efficacy and Safety of Pioglitazone Add-on in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin and Dapagliflozin: A Multicenter, Randomized, Double-blind, and Placebo-Controlled Study.

PURPOSE: The purpose of this study was to determine the efficacy and safety profile of pioglitazone compared with placebo (PBO) in patients with type 2 diabetes (T2D) inadequately controlled with metformin and dapagliflozin. METHODS: In this prospective, multicenter, randomized, double-blind, PBO-controlled trial, 366 patients with T2D who did not meet glycemic targets (7.0% ≤ glycosylated hemoglobin [HbA1c] ≤ 10.5%), despite treatment with metformin ≥1000 mg and dapagliflozin 10 mg, received either a PBO, 15 mg of pioglitazone daily (PIO15), or 30 mg of pioglitazone daily (PIO30). The primary end point was the mean change in HbA1c from baseline at 24 weeks across the groups. FINDINGS: For the 366 participants (PBO, n = 124; PIO15, n = 118; PIO30, n = 124), the mean age was 55.6 years and mean duration of diabetes was 8.7 years, with a baseline HbA1c of 7.9%. After 24 weeks, HbA1c reduced significantly in the PIO15 and PIO30 groups from baseline, with intergroup differences of -0.38% and -0.83%, respectively, compared with the PBO group. The proportion of patients with HbA1c levels <7% was significantly higher in the PIO15 and PIO30 groups than in the PBO group. The adverse event rates did not significantly differ across the groups, indicating favorable safety profiles for triple combination therapy using metformin, dapagliflozin, and pioglitazone. IMPLICATIONS: The addition of pioglitazone as a third oral antidiabetic medication is an appropriate option for patients with T2D inadequately controlled with metformin and dapagliflozin based on the resulting significant efficacy in glycemic control and favorable safety profile. CLINICALTRIALS: gov identifier: NCT04885712.

Epigenetic link between Agent Orange exposure and type 2 diabetes in Korean veterans.

Conflicting findings have been reported regarding the association between Agent Orange (AO) exposure and type 2 diabetes. This study aimed to examine whether AO exposure is associated with the development of type 2 diabetes and to verify the causal relationship between AO exposure and type 2 diabetes by combining DNA methylation with DNA genotype analyses. An epigenome-wide association study and DNA genotype analyses of the blood of AO-exposed and AO-unexposed individuals with type 2 diabetes and that of healthy controls were performed. Methylation quantitative trait locus and Mendelian randomisation analyses were performed to evaluate the causal effect of AO-exposure-identified CpGs on type 2 diabetes. AO-exposed individuals with type 2 diabetes were associated with six hypermethylated CpG sites (cg20075319, cg21757266, cg05203217, cg20102280, cg26081717, and cg21878650) and one hypo-methylated CpG site (cg07553761). Methylation quantitative trait locus analysis showed the methylation levels of some CpG sites (cg20075319, cg20102280, and cg26081717) to be significantly different. Mendelian randomisation analysis showed that CpG sites that were differentially methylated in AO-exposed individuals were causally associated with type 2 diabetes; the reverse causal effect was not significant. These findings reflect the need for further epigenetic studies on the causal relationship between AO exposure and type 2 diabetes.

Inhibition the ubiquitination of ENaC and Na,K-ATPase with erythropoietin promotes alveolar fluid clearance in sepsis-induced acute respiratory distress syndrome.

Sepsis-induced acute respiratory distress syndrome (ARDS) causes significant fatalities worldwide and lacks pharmacological intervention. Alveolar fluid clearance (AFC) plays a pivotal role in the remission of ARDS and is markedly impaired in the pathogenesis of ARDS. Here, we demonstrated that erythropoietin could effectively ameliorate lung injury manifestations and lethality, restore lung function and promote AFC in a rat model of lipopolysaccharide (LPS)-induced ARDS. Moreover, it was proven that EPO-induced restoration of AFC occurs through triggering the total protein expression of ENaC and Na,K-ATPase channels, enhancing their protein abundance in the membrane, and suppressing their ubiquitination for degeneration. Mechanistically, the data indicated the possible involvement of EPOR/JAK2/STAT3/SGK1/Nedd4-2 signaling in this process, and the pharmacological inhibition of the pathway markedly eliminated the stimulating effects of EPO on ENaC and Na,K-ATPase, and subsequently reversed the augmentation of AFC by EPO. Consistently, in vitro studies of alveolar epithelial cells paralleled with that EPO upregulated the expression of ENaC and Na,K-ATPase, and patch-clamp studies further demonstrated that EPO substantially strengthened sodium ion currents. Collectively, EPO could effectively promote AFC by improving ENaC and Na,K-ATPase protein expression and abundance in the membrane, dependent on inhibition of ENaC and Na,K-ATPase ubiquitination, and resulting in diminishing LPS-associated lung injuries.

Domain knowledge-assisted multi-objective evolutionary algorithm for channel selection in brain-computer interface systems.

Background: For non-invasive brain-computer interface systems (BCIs) with multiple electroencephalogram (EEG) channels, the key factor limiting their convenient application in the real world is how to perform reasonable channel selection while ensuring task accuracy, which can be modeled as a multi-objective optimization problem. Therefore, this paper proposed a two-objective problem model for the channel selection problem and introduced a domain knowledge-assisted multi-objective optimization algorithm (DK-MOEA) to solve the aforementioned problem. Methods: The multi-objective optimization problem model was designed based on the channel connectivity matrix and comprises two objectives: one is the task accuracy and the other one can sensitively indicate the removal status of channels in BCIs. The proposed DK-MOEA adopted a two-space framework, consisting of the population space and the knowledge space. Furthermore, a knowledge-assisted update operator was introduced to enhance the search efficiency of the population space by leveraging the domain knowledge stored in the knowledge space. Results: The proposed two-objective problem model and DK-MOEA were tested on a fatigue detection task and four state-of-the-art multi-objective evolutionary algorithms were used for comparison. The experimental results indicated that the proposed algorithm achieved the best results among all the comparative algorithms for most cases by the Wilcoxon rank sum test at a significance level of 0.05. DK-MOEA was also compared with a version without the utilization of domain knowledge and the experimental results validated the effectiveness of the knowledge-assisted mutation operator. Moreover, the comparison between DK-MOEA and a traditional classification algorithm using all channels demonstrated that DK-MOEA can strike the balance between task accuracy and the number of selected channels. Conclusion: The formulated two-objective optimization model enabled the selection of a minimal number of channels without compromising classification accuracy. The utilization of domain knowledge improved the performance of DK-MOEA. By adopting the proposed two-objective problem model and DK-MOEA, a balance can be achieved between the number of the selected channels and the accuracy of the fatigue detection task. The methods proposed in this paper can reduce the complexity of subsequent data processing and enhance the convenience of practical applications.

Infrared imaging of polydimethylsiloxane-doped upconversion particle composites.

Short-wave infrared imaging is playing an increasingly important role in present scientific research. However, the high experimental cost limits its application. Based on the upconversion fluorescence effect, we prepared a low-cost composite film for short-wave infrared imaging using upconversion particles and polydimethylsiloxane. The imaging quality and stability of the prepared composite films are examined using an infrared laser. The fluorescence density fluctuation of the composite films at 100 is only 1.2%, and the maximum value of the fluorescence power percentage error caused by the inhomogeneity is only 4.5%. Due to the affordable and easy accessibility, a typical optical laboratory can prepare and use the aforementioned technique in experiments in a short time.

Association between Vitamin D Deficiency and Clinical Parameters in Men and Women Aged 50 Years or Older: A Cross-Sectional Cohort Study.

Vitamin D deficiency (VDD) is increasingly prevalent on a global scale and is connected to chronic health issues including diabetes, obesity, and inflammation. This study aimed to investigate the association between VDD and various clinical parameters including glycated hemoglobin (HbA1c), body mass index (BMI), and inflammatory markers. This cross-sectional cohort study included Korean men and women aged 50 years and older (290 men, 125 women); VDD was classified as serum 25-hydroxyvitamin D (25[OH]D) levels below 20 ng/mL. Vitamin D deficiency was more prevalent in men (64.5%) compared to that in women (35.2%). Men with VDD had higher fat mass and HbA1c levels, lower muscle strength, and worse physical performance. Among women, VDD was associated with higher BMI, HbA1c, tumor necrosis factor-alpha (TNF-α), and creatinine levels. In women, 25(OH)D levels exhibited an inverse relationship with HbA1c, BMI, and TNF-α concentrations. However, there were no differences in the levels of interleukin-6 and interleukin-1 beta according to vitamin D status in both men and women. Vitamin D deficiency is linked to higher HbA1c, BMI, and inflammatory markers in older Korean women, thus warranting the maintenance of sufficient vitamin D levels for overall health.

Vitreous Fatty Amides and Acyl Carnitines Are Altered in Intermediate Age-Related Macular Degeneration.

Purpose: Age-related macular degeneration (AMD) is the leading cause of visual impairment worldwide. In this study, we aimed to investigate the vitreous humor metabolite profiles of patients with intermediate AMD using untargeted metabolomics. Methods: We performed metabolomics using high-resolution liquid chromatography mass spectrometry on the vitreous humor of 31 patients with intermediate AMD and 30 controls who underwent vitrectomy for epiretinal membrane with or without cataract surgery. Univariate analyses after false discovery rate correction were performed to discriminate the metabolites and identify the significant metabolites of intermediate AMD. For biologic interpretation, enrichment and pathway analysis were conducted using MetaboAnalyst 5.0. Results: Of the 858 metabolites analyzed in the vitreous humor, 258 metabolites that distinguished patients with AMD from controls were identified (P values < 0.05). Ascorbic acid and uric acid levels increased in the AMD group (all P values < 0.05). The acyl carnitines, such as acetyl L-carnitine (1.37-fold), and fatty amides, such as anandamide (0.9-fold) and docosanamide (0.67-fold), were higher in patients with intermediate AMD. In contrast, nicotinamide (-0.55-fold), and succinic acid (-1.69-fold) were lower in patients with intermediate AMD. The metabolic pathway related oxidation of branched chain fatty acids and carnitine synthesis showed enrichment. Conclusions: Multiple metabolites related to fatty amides and acyl carnitine were found to be increased in the vitreous humor of patients with intermediate AMD, whereas succinic acid and nicotinamide were reduced, suggesting that altered metabolites related to fatty amides and acyl carnitines and energy metabolism may be implicated in the etiology of AMD.

Fatty acid amides as potential circulating biomarkers for sarcopenia.

BACKGROUND: Sarcopenia is characterized by a progressive decrease in skeletal muscle mass and function with age. Given that sarcopenia is associated with various metabolic disorders, effective metabolic biomarkers for its early detection are required. We aimed to investigate the metabolic biomarkers related to sarcopenia in elderly men and perform experimental studies using metabolomics. METHODS: Plasma metabolites from 142 elderly men, comprising a sarcopenia group and an age-matched control group, were measured using global metabolome profiling. Muscle and plasma samples from an aging mouse model of sarcopenia, as well as cell media and cell lysates during myoblast differentiation, were analysed based on targeted metabolome profiling. Based on these experimental results, fatty acid amides were quantified from human plasma as well as human muscle tissues. The association of fatty acid amide levels with sarcopenia parameters was evaluated. RESULTS: Global metabolome profiling showed that fatty acid amide levels were significantly different in the plasma of elderly men with sarcopenia (all Ps < 0.01). Consistent with these results in human plasma, targeted metabolome profiling in an aging mouse model of sarcopenia showed decreased levels of fatty acid amides in plasma but not in muscle tissue. In addition, the levels of fatty acid amides increased in cell lysates during muscle cell differentiation. Targeted metabolome profiling in men showed decreased docosahexaenoic acid ethanolamide (DHA EA) levels in the plasma (P = 0.016) but not in the muscle of men with sarcopenia. DHA EA level was positively correlated with sarcopenia parameters such as skeletal muscle mass index (SMI) and handgrip strength (HGS) (P = 0.001, P = 0.001, respectively). The area under the receiver-operating characteristic curve (AUC) for DHA EA level ≤ 4.60 fmol/µL for sarcopenia was 0.618 (95% confidence interval [CI]: 0.532-0.698). DHA EA level ≤ 4.60 fmol/µL was associated with a significantly greater likelihood of sarcopenia (odds ratio [OR]: 2.11, 95% CI: 1.03-4.30), independent of HGS. The addition of DHA EA level to age and HGS significantly improved the AUC from 0.620 to 0.691 (P = 0.0497). CONCLUSIONS: Our study demonstrated that fatty acid amides are potential circulating biomarkers in elderly men with sarcopenia. DHA EA, in particular, strongly related to muscle mass and strength, can be a key metabolite to become a reliable metabolic biomarker for sarcopenia. Further research on fatty acid amides will provide insights into the metabolomic changes relevant to sarcopenia from an aging perspective.