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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Causal Association of Obesity and Dyslipidemia with Type 2 Diabetes: A Two-Sample Mendelian Randomization Study.

Recent studies have suggested an association between obesity and dyslipidemia in the development of type 2 diabetes (T2D). The purpose of this study was to explore the causal effects of obesity and dyslipidemia on T2D risk in Asians. Two-sample Mendelian randomization (MR) analyses were performed to assess genetically predicted obesity using body mass index (BMI) and dyslipidemia using high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TCHL), and triglycerides (TG) versus T2D susceptibility using genome-wide association study (GWAS) results derived from the summary statistics of Biobank Japan (n = 179,000) and DIAbetes Meta-ANalysis of Trans-Ethnic association studies (n = 50,533). The MR analysis demonstrated evidence of a causal effect of higher BMI on the risk of T2D (odds ratio (OR) > 1.0, p < 0.05). In addition, TG showed a protective effect on the risk of T2D (ORs 0.68-0.85). However, HDL, LDL, and TCHL showed little genetic evidence supporting a causal association between dyslipidemia and T2D. We found strong genetic evidence supporting a causal association of BMI with T2D. Although HDL, LDL, and TCHL did not show a causal association with T2D, TG had a causal relationship with the decrease of T2D. Although it was predicted that TG would be linked to a higher risk of T2D, it actually exhibited a paradoxical protective effect against T2D, which requires further investigation.

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.

New-onset type 1 diabetes mellitus as a delayed immune-related event after discontinuation of nivolumab: A case report.

RATIONALE: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, they may cause immune-related adverse events. Although there have been a few reports of new-onset type 1 diabetes mellitus (T1DM) during ICI treatment, T1DM as a delayed immune-related event after discontinuing immunotherapy is extremely rare. Herein, we report the case of an elderly veteran who presented with diabetic ketoacidosis 4 months after the discontinuation of treatment with nivolumab. PATIENT CONCERNS: A 74-year-old veteran was treated with second-line nivolumab for advanced non-small cell lung cancer. After 9 treatment cycles, the administration was discontinued due to fatigue. Four months later, he was admitted to the emergency department in a stuporous mental state and hyperglycemia, with high glycosylated hemoglobin levels (10.6%). C-peptide levels were significantly decreased, with negative islet autoantibodies. DIAGNOSES: We diagnosed nivolumab-induced T1DM. There were no laboratory results indicating a new thyroid dysfunction or adrenal insufficiency, which are typical endocrine adverse reactions. INTERVENTIONS: Since the hypothalamic and pituitary functions were preserved and only the pancreatic endocrine capacity was impaired, we administered continuous intravenous insulin injections, with fluid and electrolyte replacement. OUTCOMES: His serum glucose levels decreased, and symptoms improved; hence, on the 8 day of hospitalization, we switched to multiple daily insulin injections. LESSONS: The present case indicates that regular glucose monitoring and patient education are needed for diabetic ketoacidosis after the discontinuation of ICI therapy.

A Genome-Wide Association Study of Genetic Variants of Apolipoprotein A1 Levels and Their Association with Vitamin D in Korean Cohorts.

Dyslipidemia is an important independent risk factor for cardiovascular disease (CVD). Specifically, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and the ApoB/A1 ratio have been linked to CVD. We conducted a genome-wide association study meta-analysis of two Korean cohorts containing a total of 12,924 patients to identify novel single nucleotide polymorphisms (SNPs) associated with ApoA1 and ApoB levels and the ApoB/A1 ratio. Additionally, an expression quantitative trait locus (eQTL) and differentially expressed genes (DEGs) analysis were performed. The statistically significant eQTL, DEG, and Gene Ontology (GO) results were used to explore the predicted interaction networks and retrieve the interacting genes and proteins. We identified three novel SNPs (rs11066280, p = 3.46 × 10−21; rs1227162, p = 2.98 × 10−15; rs73216931, p = 5.62 × 10−9) associated with ApoA1. SNP rs73216931 was an eQTL for KMT5A in the pancreas and whole blood. The network analysis revealed that HECTD4 and MYL2:LINC1405 are associated with AKT1. Our in silico analysis of ApoA1 genetic variants revealed heart muscle-related signals. ApoA1 also correlated positively with vitamin D, and genes associated with ApoA1 and vitamin D were found. Our data imply that more research into ApoA1 is needed to understand the links between dyslipidemia and CVD and vitamin D and CVD.

Evaluation of NOTCH family genes' expression and prognostic value in prostate cancer.

Background: Abnormal regulation of the NOTCH signaling pathway in prostate cancer (PCa) can promote tumorigenesis, progression, and T cell exhaustion. However, there has not been a comprehensive analysis of NOTCH family genes (NOTCHs) as potential therapeutic targets and prognostic biomarkers for PCa patients. Methods: NOTCHs expressions in various types of cancer tissues and normal adjacent tissues in the TIMER and UALCAN database were screened. Immunohistochemistry (IHC) and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) were applied to validate the expression pattern of NOTCHs in clinical samples. The relationships of NOTCHs expression and clinicopathologic parameters or disease-free survival (DFS) were evaluated via GEPIA2 and UALCAN. A proteins network was built using STRING and GeneMANIA. Additionally, NOTCHs mutation status was analyzed by cBioportal. Finally, we used GDSC and TIMER to investigate NOTCH signaling-related drugs and immune cell infiltration. Results: The transcriptional levels of NOTCH1 and NOTCH4 in PCa tissues were significantly lower than in normal tissues, which was further validated in clinical patients' tissue samples. Furthermore, NOTCH1, NOTCH3, and NOTCH4 expressions in PCa were associated with worse DFS. Interestingly, there was a significant positive correlation between NOTCHs and androgen receptor (AR), but not with AR-related genes (KLK3 and TMPRSS2). Finally, we found that NOTCHs expressions were remarkably associated with infiltration of B cells, CD8+/CD4+ T cells, macrophages, neutrophils, and dendritic cells, which indicated that NOTCHs mutation status might be a potential therapeutic target for -tinib antineoplastic drugs. Conclusions: The expression and mutation of NOTCH1-4 in PCa were associated with disease progression, prognosis, immune cell infiltration, and drug sensitivity.

Clinical Outcomes of Repeated Radioactive Iodine Therapy for Graves' Disease.

BACKGRUOUND: Radioactive iodine (RAI) therapy is a successful therapeutic modality for Graves' disease. However, RAI therapy can fail, and RAI therapy after antithyroid drugs (ATDs) has a lower remission rate. Therefore, many patients require repeated RAI therapy. This study investigated the clinical outcomes of repeated RAI therapy for Graves' disease. METHODS: Patients who underwent RAI therapy as second-line therapy after failure of ATD treatment between 2001 and 2015 were reviewed. Remission was defined as hypothyroid or euthyroid status without ATD, and with or without levothyroxine at 12 months after RAI therapy. RESULTS: The 1-year remission rate after 2nd RAI therapy (66%, 152/230) is significantly higher than that after 1st RAI therapy (48%, 393/815) or long-term ATD treatment after 1st RAI therapy failure (42%). The clinical response to 2nd RAI therapy was more rapid. The median time intervals from the 2nd RAI therapy to ATD discontinuation (1.3 months) and to the start of levothyroxine replacement (2.5 months) were significantly shorter than those for the 1st RAI therapy. A smaller goiter size, a longer time interval between the 1st and 2nd RAI therapies, and a longer ATD discontinuation period predicted remission after the 2nd RAI therapy. Finally, in 78 patients who failed the 2nd RAI therapy, the mean ATD dosage significantly reduced 5.1 mg over 12 months. CONCLUSION: Repeated RAI therapy can be a good therapeutic option, especially in patients with smaller goiters and those who are more responsive to the 1st RAI therapy.

Unveiling genetic variants for age-related sarcopenia by conducting a genome-wide association study on Korean cohorts.

Sarcopenia is an age-related disorder characterised by a progressive decrease in skeletal muscle mass. As the genetic biomarkers for sarcopenia are not yet well characterised, this study aimed to investigate the genetic variations related to sarcopenia in a relatively aged cohort, using genome-wide association study (GWAS) meta-analyses of lean body mass (LBM) in 6961 subjects. Two Korean cohorts were analysed, and subgroup GWAS was conducted for appendicular skeletal muscle mass (ASM) and skeletal muscle index. The effects of significant single nucleotide polymorphisms (SNPs) on gene expression were also investigated using multiple expression quantitative trait loci datasets, differentially expressed gene analysis, and gene ontology analyses. Novel genetic biomarkers were identified for LBM (rs1187118; rs3768582) and ASM (rs6772958). Their related genes, including RPS10, NUDT3, NCF2, SMG7, and ARPC5, were differently expressed in skeletal muscle tissue, while GPD1L was not. Furthermore, the 'mRNA destabilisation' biological process was enriched for sarcopenia. Our study identified RPS10, NUDT3, and GPD1L as significant genetic biomarkers for sarcopenia. These genetic loci were related to lipid and energy metabolism, suggesting that genes involved in metabolic dysregulation may lead to the pathogenesis of age-related sarcopenia.

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.