Uncovering the health implications of abandoned mines through protein profiling of local residents.

Residents in areas with abandoned mines risk significant exposure to abundant heavy metals in the environment. However, current clinical indicators cannot fully reflect the health changes associated with abandoned mine exposure. The aim of this study was to identify biological changes in the residents of abandoned mine areas via proteomic analysis of their blood. Blood samples were collected from abandoned mine and control areas, and mass spectrometry was used for protein profiling. A total of 138 unique or common proteins that were differentially expressed in low-exposure abandoned mine area (LoAMA) or high-exposure abandoned mine area (HiAMA) compared to non-exposure control area (NEA) were analyzed, and identified 4 clusters based on functional similarity. Among the 10 proteins that showed specific change in LoAMA, 4 proteins(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) were cluded in cluster 1(plasma lipoprotein remodeling), and linked to proteins that showed specific change in protein expression in HiAMA. Therefore, it is suggested that 4 proteins are changed at low exposure to an abandoned mine (or initial exposure), and then at high exposure, changes in various proteins involved in linked plasma lipoprotein remodeling are induced, which might triggered by the 4 proteins. Interestingly, in addition to plasma lipoprotein remodeling, proteins involved in other functional networks were changed in the high exposure group. These were all directly or indirectly linked to the 4 biomarkers(Apolipoprotein M, Apolipoprotein E, Apolipoprotein L1, and Cholesteryl ester transfer protein) that changed during low exposure. This suggests their potential utility in identifying areas impacted by abandoned mines. Especially, proteins involved in lipid metabolism and renal function-related diseases in individuals exposed to heavy metals in abandoned mine areas were correlated. Chronic kidney disease is predominantly instigated by cardiovascular disease and is commonly accompanied by dyslipidemia.

The complete mitochondrial genome of Gobionotothen gibberifrons (Perciformes, Nototheniidae).

The humped rockcod, Gobionotothen gibberifrons, is an Antarctic fish of the genus Gobionotothen in the family Nototheniidae and order Perciformes. To date, little biological information has been recorded about the genus Gobionotothen. Here, we report the first complete mitogenome of the genus Gobionotothen. The mitochondrial genome of G. gibberifrons is 18,631 bp in length, comprising 13 protein-coding genes, 24 tRNA genes (trnP-UGG and trnT-UGU were duplicated), 2 rRNA genes, and non-coding control regions. The base composition was 53.74% for A + T and 46.26% for G + C. This new mitochondrial genome of G. gibberifrons provides basic information for further phylogenetic analysis, suggesting the necessity to exploit a variety of newly discovered mitogenome sequences to infer inconclusive evolutionary relationships in Antarctic fishes.

Epoxy-Based Copper (Cu) Sintering Pastes for Enhanced Bonding Strength and Preventing Cu Oxidation after Sintering.

The investigation of interconnection technologies is crucial for advancing semiconductor packaging technology. This study delved into the various methods of achieving electrical interconnections, focusing on the sintering process and composition of the epoxy. Although silver (Ag) has traditionally been utilized in the sintering process, its high cost often precludes widespread commercial applications. Copper (Cu) is a promising alternative that offers advantages, such as cost-effectiveness and high thermal and electrical conductivities. However, the mechanical robustness of the oxide layers formed on Cu surfaces results in several challenges. This research addresses these challenges by integrating epoxy, which has advantages such as adhesive capabilities, chemical resistance, and robust mechanical properties. The chemical reactivity of the epoxy was harnessed to both fortify adhesion and inhibit oxide layer formation. However, the optimal sintering performance required considering both the composite composition (20 wt% epoxy) and the specific sintering conditions (pre-heating at 200 °C and sintering at 250 °C). The experimental findings reveal a balance in the incorporation of epoxy (20 wt%) for the desired electrical and mechanical properties. In particular, the bisphenol A epoxy (Da)-containing sintered Cu chip exhibited the highest lab shear strength (35.9 MPa), whereas the sintered Cu chip without epoxy represented the lowest lab shear strength of 2.7 MPa. Additionally, the introduction of epoxy effectively curtailed the onset of oxidation in the sintered Cu chips, further enhancing their durability. For instance, 30 days after sintering, the percentage of oxygen atoms in the Da-containing sintered Cu chip (4.5%) was significantly lower than that in the sintered Cu chip without epoxy (37.6%), emphasizing the role of epoxy in improving Cu oxidation resistance. Similarly, the samples sintered with bisphenol-based epoxy binders exhibited the highest electrical and thermal conductivities after 1 month. This study provides insights into interactions between epoxy, carboxylic acid, solvents, and Cu during sintering and offers a foundation for refining the sintering conditions.

Cadmium-associated protein changes in residents of contaminated areas: Abandoned mine and smelter.

Cadmium (Cd), a serious environmental contaminant, is associated with adverse health effects. However, the specific changes that the human body experiences in response to exposure to varying concentrations of cadmium remain unknown. The high levels of heavy metal contamination, especially Cd, in abandoned mines and smelter sites make them ideal locations to investigate the physiological manifestations of Cd exposure. This study found that individuals inhabiting abandoned mine and smelter areas had higher concentrations of Cd in their urine and blood compared to those living outside these areas (i.e., the controls). Furthermore, proteomic profiling of blood samples from all study groups was performed to identify proteomic biomarkers associated with chronic and severe Cd exposure. This analysis showed statistically significant correlations between urine Cd levels and sixteen proteins. Among these proteins, seven exhibited significantly altered expressions in samples from contaminated areas compared with those from control areas. Therefore, these proteins were selected as potential markers representing Cd-related protein alterations. Multiple reaction monitoring analysis was performed to validate the expression patterns of the proteins and four proteins were found to exhibit consistent trends. The findings show that Cd exposure significantly affects the expression of certain proteins in the human body. Understanding the underlying mechanisms and diseases associated with Cd-induced protein alterations can aid in the development of effective preventive and therapeutic strategies for individuals exposed to Cd-linked pollution.

Association between age-related macular degeneration and risk of incident cancer.

BACKGROUND/AIMS: Age-related macular degeneration (AMD) and cancer may share similar risk factors, indicating possible common pathogenic pathways. We aimed to describe the site-specific cancer risk based on the relationship of AMD with visual disability (VD) status. METHODS: This was a population-based cohort study using data from the Korean National Health Insurance Service database (2009-2019) including patients who participated in a national health screening programme in 2009. The subjects were categorised based on the presence of AMD and VD. The occurrence of cancer was identified using principal diagnosis according to the International Classification of Disease, 10th revision codes in claims data. The Cox regression hazard model was used to compare HRs of site-specific cancer. RESULTS: Among 4 088 814 participants, 51 596 had AMD of which 3683 subjects had VD. The mean follow-up period was 9.6 years. The overall cancer risk was generally null, but the risk of hypervascular cancer such as thyroid cancer (adjusted HR (aHR) 1.10, 95% CI 1.00 to 1.20) and renal cancer (aHR 1.16, 95% CI 1.00 to 1.33) was higher and the risk of stomach cancer (aHR 0.89, 95% CI 0.84 to 0.94) was lower in the AMD group than in the non-AMD group. CONCLUSION: This study demonstrated a possible association between AMD and several cancers. Increased renal and thyroid cancer risk among patients with AMD could indicate that AMD is associated with hypervascular cancer. Further studies in which additional databases are used and the underlying detailed mechanisms evaluated are needed to validate our results.

Iliopsoas plane block does not improve pain after primary total hip arthroplasty in the presence of multimodal analgesia: a single institution randomized controlled trial.

BACKGROUND: The clinical analgesic efficacy of iliopsoas plane block remains a subject of discussion. This study aimed to assess the analgesic efficacy of iliopsoas plane block under general anesthesia using multimodal analgesia. METHODS: Fifty-six adult patients who underwent elective primary hip arthroplasty were enrolled. Patients were randomized to receive either a single-shot iliopsoas plane block (10 mL 0.75% ropivacaine with 1:200 000 epinephrine) or a sham block (10 mL normal saline). All patients received general anesthesia, multimodal analgesia (preoperative buprenorphine patch, 5 µg/h), intraoperative intravenous dexamethasone (8 mg) and nefopam (20 mg), and round-the-clock acetaminophen and celecoxib. The primary outcome was the numeric rating scale pain score at rest 6 hour after surgery. RESULTS: Iliopsoas plane block did not have a notable advantage over the sham block in terms of pain relief at rest, as assessed by the numeric rating scale score, 6 hour after total hip arthroplasty (iliopsoas plane block: median, 4.0; IQR, 2.0-5.8; sham: median, 5.5; IQR, 2.3-6.8; median difference, -1.0; 95% CI -2.0 to 0.0; p≥0.999). Linear mixed model analysis showed no differences in pain scores, opioid consumption, quadriceps strength, or quality of recovery between the groups. CONCLUSIONS: Iliopsoas plane block did not improve postoperative analgesia following total hip arthroplasty under general anesthesia with a multimodal analgesic regimen. The blockade of sensory femoral branches supplying the anterior hip capsule using iliopsoas plane block may not yield additional benefits concerning patient outcomes in the aforementioned clinical context. TRIAL REGISTRATION NUMBER: NCT05212038, https://clinicaltrials.gov/ct2/show/NCT05212038.

Discovery and validation of protein biomarkers for monitoring the effectiveness of drug treatment for major depressive disorder.

Major depressive disorder (MDD) has a high prevalence worldwide. Although the economic burden of depression increases annually, the proportion of patients with MDD receiving treatment did not increase between 2010 and 2018, suggesting an unmet treatment need. The burden of long-term treatment for depression is borne by patients. In this context, biomarkers associated with drug-treatment responses can be used as reference indicators to reduce unnecessary treatment and costs. Changes in biomolecules in response to drug treatment for depression and drug-treatment response markers have been studied extensively. The Hamilton Depression Rating Scale (HAM-D) is mainly used as an indicator of response and remission; however, it is difficult to determine whether the medication contributes to recovery when evaluating the effect of drug treatment for depression based on this assessment. Therefore, it is necessary to monitor the effect of medication compared to normal health conditions. Here, serum protein levels were compared using liquid chromatography-tandem mass spectrometry among a group of patients with depression who did not receive medication, a group of patients receiving medication, and a control group. Eight selected biomarkers, including Apolipoproteins A-I, Complement factor H, Complement C5, Complement C1q subcomponent subunit B, Alpha-2-HS-glycoprotein, Complement C1q subcomponent subunit C, Vitamin D-binding protein and Corticosteroid-binding globulin were distinguished between disease states, and protein levels in the drug-treated group were similar to those in the control group. These markers can be used to monitor the effectiveness of drug treatment.

Partial in vivo reprogramming enables injury-free intestinal regeneration via autonomous Ptgs1 induction.

Tissue regeneration after injury involves the dedifferentiation of somatic cells, a natural adaptive reprogramming that leads to the emergence of injury-responsive cells with fetal-like characteristics. However, there is no direct evidence that adaptive reprogramming involves a shared molecular mechanism with direct cellular reprogramming. Here, we induced dedifferentiation of intestinal epithelial cells using OSKM (Oct4, Sox2, Klf4, and c-Myc) in vivo. The OSKM-induced forced dedifferentiation showed similar molecular features of intestinal regeneration, including a transition from homeostatic cell types to injury-responsive-like cell types. These injury-responsive-like cells, sharing gene signatures of revival stem cells and atrophy-induced villus epithelial cells, actively assisted tissue regeneration following damage. In contrast to normal intestinal regeneration involving Ptgs2 induction, the OSKM promotes autonomous production of prostaglandin E2 via epithelial Ptgs1 expression. These results indicate prostaglandin synthesis is a common mechanism for intestinal regeneration but involves a different enzyme when partial reprogramming is applied to the intestinal epithelium.

Association between plant protein intake and grip strength in Koreans aged 50 years or older: Korea National Health and Nutrition Examination Survey 2016-2018.

BACKGROUND/OBJECTIVES: We investigated the association of plant and animal protein intake with grip strength in Koreans aged ≥ 50 yrs. SUBJECTS/METHODS: The data was collected from 3,610 men and 4,691 women (≥ 50 yrs) from the 2016-2018 Korea National Health and Nutrition Examination Survey. We calculated the total energy intake, and the intake of animal and plant protein and collected dietary data using 1-day 24-h dietary recalls. Low grip strength (LGS) was defined as the lowest quintile (men: up to 26.8 kg, women: up to 15.7 kg). The association of protein intake with grip strength was examined using Pearson's correlation and multiple linear regression analysis. RESULTS: The results proved that participants with LGS had lower daily energy, protein and fat intake, and percent energy from protein than those with normal or high grip strength (P < 0.0001). Total energy intake, animal protein, and plant protein were positively associated with grip strength. A higher intake of total plant protein (P for trend = 0.004 for men, 0.05 for women) and legumes, nuts, and seeds (LNS) protein (P for trend = 0.01 for men, 0.02 for women) was significantly associated with a lower prevalence of LGS. However, non-LNS plant protein intake was not associated with LGS (P for trend = 0.10 for men, 0.15 for women). In women, a higher total animal protein intake was significantly associated with decreased LGS (P for trend = 0.03). CONCLUSIONS: Higher total plant protein and LNS protein intake are negatively associated with LGS.

Copper Sintering Pastes with Various Polar Solvents and Acidic Activators.

Devices in the developing semiconductor market require high density, high integration, and detailed processing. Conventional wire bonding is inappropriate for fine-sized devices, and connected wires can be damaged by heat generation and external physical impact. Soldering is also used in advanced packaging technologies. However, disturbances and overhead joints can occur during bonding. Thus, sintering has been extensively utilized to overcome these drawbacks. Sintering pastes are pressurized and bonded, resulting in stable bonding during sintering. In this study, the composition of the Cu sintering material was examined using diverse additives and solvents. We manufactured sintering materials comprising Cu (1 µm), a solvent [methanol (MeOH), ethanol (EtOH), or ethylene glycol (EG)] and an acidic additive (benzoic acid, phthalic acid, or hexanoic acid). After the sintering process, the mechanical and electrical characteristics were compared to determine the optimal composition and bonding conditions. The optimum ratios between the acid and solvent were 4:6 (MeOH and EtOH) and 2:8 (EG) due to the high viscosity and effective long-term storage. All samples using EtOH as the solvent exhibited the highest sintering performances. The aromatic and carboxylic groups substantially improved the sintering performance and increased the electrical conductivity. Based on the O1s/Cu2p ratio (2.23%), the best sintering composition was EtOH/PA, which showed the highest electrical conductivity (ca. 104 S/m) and strength (34.0 MPa). The sintering process using various additives and solvents can be helpful to determine the sintering conditions while maintaining the electrical properties.

Occupational characteristics and risk factors associated with endometriosis among Korean female workers.

Endometriosis is a chronic and debilitating condition that affects daily working life. Characterization of the factors associated with endometriosis in the working population can facilitate the development of prevention and intervention strategies for those at risk of endometriosis. This population-based retrospective study was conducted using the 2007-2015 National Health Insurance Service-Female Employees database. Overall, 151,386 female workers aged 15-64 years were included in the study. Participants with endometriosis were identified using the diagnosis codes in the claims data. Multivariable Cox regression analyses were used to evaluate the effect of sociodemographic, lifestyle, health, and occupational factors on endometriosis risk. Of the 151,386 participants, 4,457 were diagnosed with endometriosis. The risk of endometriosis was significantly higher in 41-60 years group (HR = 1.47 (95% CI, 1.06-2.04)) and in those with body mass index (BMI) < 18.5 kg/m2 (HR = 1.16 (95% CI, 1.05-1.27)) than 15-20 years group and those with normal BMI, respectively. According to the international standard industrial classification, occupational groups with financial and insurance activities, public administration and defence, compulsory social security, and manufacturing were at a higher risk of endometriosis. Although there was no significant association between the risk of endometriosis and type of work, the cumulative prevalence of endometriosis from 2007 to 2015 continued to rise in office workers, manual workers, and both types of workers together. The risk of endometriosis was closely linked to the occupational characteristics of female workers. This study provides a foundation for developing occupational safety and health guidelines for female workers.

Serum Protein Profiling Reveals a Decrease in Apolipoprotein A-IV During a Clinical Depressive Mood State.

Purpose: Depressive mood is a major psychiatric symptom that causes serious disturbances in daily life. Unlike physical symptoms, psychiatric symptoms are more difficult to evaluate objectively. Therefore, we aimed to discover biomarkers that reflect changes in serum protein metabolism during a clinical depressive mood. Methods: Serum protein profiling was conducted in participants who were not experiencing a current depressive episode (healthy individuals and patients in remission). Serum proteins were identified and quantified using liquid chromatography-tandem mass spectrometry. Differentially expressed proteins with a p-value <0.05 were selected, and candidate biomarkers were verified using multiple reaction monitoring analysis for absolute quantification. Results: Apolipoprotein A-IV levels were lower in the group with a current episode of depression than in the remission and healthy control groups. Further, fibronectin levels were also lower in the group with a current episode of depression than in the healthy control group but not in the remission group. Conclusion: We found that apolipoprotein A-IV-mediated inflammation is involved in clinical depressive moods, possibly by inducing neurological changes in the brain. Therefore, apolipoprotein A-IV and fibronectin levels may be explored as potentially novel biomarkers for detecting a current episode of depression.

Stable clinical risk prediction against distribution shift in electronic health records.

The availability of large-scale electronic health record datasets has led to the development of artificial intelligence (AI) methods for clinical risk prediction that help improve patient care. However, existing studies have shown that AI models suffer from severe performance decay after several years of deployment, which might be caused by various temporal dataset shifts. When the shift occurs, we have access to large-scale pre-shift data and small-scale post-shift data that are not enough to train new models in the post-shift environment. In this study, we propose a new method to address the issue. We reweight patients from the pre-shift environment to mitigate the distribution shift between pre- and post-shift environments. Moreover, we adopt a Kullback-Leibler divergence loss to force the models to learn similar patient representations in pre- and post-shift environments. Our experimental results show that our model efficiently mitigates temporal shifts, improving prediction performance.

Discovery and validation of metabolite markers in bloodstains for bloodstain age estimation.

Bloodstain age estimation involves measuring time-dependent changes in the levels of biomolecules in bloodstains. Although several studies have identified bloodstain metabolites as markers for estimating bloodstain age, none have considered sex, age-related metabolomic differences, or long-time bloodstain age. Therefore, we aimed to identify metabolite markers for estimating the age of bloodstains at weekly intervals within 28 days and validate them through multiple reaction monitoring. Adenosine 5'-monophosphate, choline, and pyroglutamic acid were selected as markers. Seven metabolites were validated, including five previously reported metabolites, ergothioneine, hypoxanthine, L-isoleucine, L-tryptophan, and pyroglutamic acid. Choline and hypoxanthine can be used to differentiate bloodstains between days 0 and 14 after deposition at weekly intervals, whereas L-isoleucine and L-tryptophan can help distinguish bloodstains between 7 days before and 14 days after deposition. Evaluation of the changes in metabolite levels according to sex and age revealed that the average levels of all seven metabolites were higher in women on day 0. Moreover, the level of ergothioneine was significantly higher in elderly individuals than in young individuals at all time points. In this study, we confirmed the potential effectiveness of metabolites in bloodstains as forensic markers and provided a new perspective on metabolomic approaches linked to forensic science.

Phase Engineering of 2D Materials.

Polymorphic 2D materials allow structural and electronic phase engineering, which can be used to realize energy-efficient, cost-effective, and scalable device applications. The phase engineering covers not only conventional structural and metal-insulator transitions but also magnetic states, strongly correlated band structures, and topological phases in rich 2D materials. The methods used for the local phase engineering of 2D materials include various optical, geometrical, and chemical processes as well as traditional thermodynamic approaches. In this Review, we survey the precise manipulation of local phases and phase patterning of 2D materials, particularly with ideal and versatile phase interfaces for electronic and energy device applications. Polymorphic 2D materials and diverse quantum materials with their layered, vertical, and lateral geometries are discussed with an emphasis on the role and use of their phase interfaces. Various phase interfaces have demonstrated superior and unique performance in electronic and energy devices. The phase patterning leads to novel homo- and heterojunction structures of 2D materials with low-dimensional phase boundaries, which highlights their potential for technological breakthroughs in future electronic, quantum, and energy devices. Accordingly, we encourage researchers to investigate and exploit phase patterning in emerging 2D materials.

Impact of dementia and drug compliance on patients with acute myocardial infarction.

BACKGROUND: In South Korea, the number of people with dementia is rising at a worrisome rate, and many of them also have acute myocardial infarction (AMI), a disease with a high mortality rate. HYPOTHESIS: We speculated that dementia and drug compliance have significant impact on the mortality of patients with AMI. METHODS: The study derived data from the National Health Insurance Service-Senior for a retrospective cohort study. The total number of patients diagnosed with AMI for the first time between 2007 and 2013 was 16 835, among whom 2021 had dementia. Medication possession ratio (MPR) was used to assess medication adherence. RESULTS: AMI patients with dementia had unfavorable baseline characteristics; they had significantly higher risk of all-cause mortality (hazard ratio [HR]: 2.49; 95% confidence interval [CI]: 2.34-2.66; p < .001) and lower MPR (aspirin: 21.9% vs. 42.8%; p < .001). AMI patients were stratified by presence of dementia and medication adherence, and the survival rate was the highest among those with no dementia and good adherence, followed by those with no dementia and poor adherence, those with dementia and good adherence, and those with dementia and poor adherence. The multivariable analysis revealed that dementia (HR: 1.64; 95% CI: 1.53-1.75; p < .001) and poor adherence to medication (HR: 1.60; 95% CI: 1.49-1.71; p < .001) had a significant association with all-cause mortality in AMI patients. CONCLUSIONS: AMI patients with dementia have a higher mortality rate. Their prognosis is negatively affected by their poorer medication adherence than patients without dementia.

Gene editing with 'pencil' rather than 'scissors' in human pluripotent stem cells.

Owing to the advances in genome editing technologies, research on human pluripotent stem cells (hPSCs) have recently undergone breakthroughs that enable precise alteration of desired nucleotide bases in hPSCs for the creation of isogenic disease models or for autologous ex vivo cell therapy. As pathogenic variants largely consist of point mutations, precise substitution of mutated bases in hPSCs allows researchers study disease mechanisms with "disease-in-a-dish" and provide functionally repaired cells to patients for cell therapy. To this end, in addition to utilizing the conventional homologous directed repair system in the knock-in strategy based on endonuclease activity of Cas9 (i.e., 'scissors' like gene editing), diverse toolkits for editing the desirable bases (i.e., 'pencils' like gene editing) that avoid the accidental insertion and deletion (indel) mutations as well as large harmful deletions have been developed. In this review, we summarize the recent progress in genome editing methodologies and employment of hPSCs for future translational applications.

High-molecular-weight DNA extraction for long-read sequencing of plant genomes: An optimization of standard methods.

Premise: Developing an effective and easy-to-use high-molecular-weight (HMW) DNA extraction method is essential for genomic research, especially in the era of third-generation sequencing. To efficiently use technologies capable of generating long-read sequences, it is important to maximize both the length and purity of the extracted DNA; however, this is frequently difficult to achieve with plant samples. Methods and Results: We present a HMW DNA extraction method that combines (1) a nuclei extraction method followed by (2) a traditional cetyltrimethylammonium bromide (CTAB) DNA extraction method for plants with optimized extraction conditions that influence HMW DNA recovery. Our protocol produced DNA fragments (percentage of fragments >20 kbp) that were, on average, ca. five times longer than those obtained using a commercial kit, and contaminants were removed more effectively. Conclusions: This effective HMW DNA extraction protocol can be used as a standard protocol for a diverse array of taxa, which will enhance plant genomic research.

Long-term mortality and cardiovascular events of seven angiotensin receptor blockers in hypertensive patients: Analysis of a national real-world database: A retrospective cohort study.

Background and Aims: Although many angiotensin receptor blockers (ARBs) are widely used, comparative data regarding their impact on clinical outcomes are limited. We aimed to compare the clinical effectiveness of seven ARBs on long-term cardiovascular outcomes in Korean patients with hypertension. Methods: Using the Korean National Health Insurance Service database, the data of 780,785 patients with hypertension without cardiovascular disease (CVD) who initiated ARB treatment (candesartan, fimasartan, irbesartan, losartan, olmesartan, telmisartan, or valsartan) in 2014 and underwent this treatment for more than 6 months, were analyzed. Cox-regression analysis was performed using Losartan as a comparator, as it was the most widely used drug, by adjusting age, sex, diabetes, dyslipidemia, smoking, alcohol drinking, exercise, body mass index, systolic blood pressure, albuminuria, estimated glomerular filtration rate, and concomitant medications. The occurrence of mortality and the rate of major adverse cardiovascular events (MACEs) of the six ARBs was compared with that of losartan. Results: The median follow-up duration was 5.94 (interquartile range, 5.87-5.97) years. In the crude analysis of all-cause mortality and MACEs, fimasartan exhibited the lowest event rates. In the Cox-regression analysis with adjustment, there was no significant difference in all-cause mortality among ARBs. The risk of MACEs with ARBs was similar to that with losartan, although the risks with irbesartan (hazard ratio [HR], 1.079; 95% confidence interval [CI], 1.033-1.127; p = 0.007) and candesartan (HR: 1.066; 95% CI, 1.028-1.106; p = 0.015) were slightly higher. Conclusion: In a Korean population of patients with hypertension without CVD, six different ARBs showed similar efficacy to losartan in terms of long-term mortality and MACEs. Further well-designed prospective studies are required to confirm our findings.

Anti-Aging and Lightening Effects of Au-Decorated Zeolite-Based Biocompatible Nanocomposites in Epidermal Delivery Systems.

The main challenges in developing zeolites as cosmetic drug delivery systems are their cytotoxicities and the formation of drug-loading pore structures. In this study, Au-decorated zeolite nanocomposites were synthesized as an epidermal delivery system. Thus, 50 nm-sized Au nanoparticles were successfully deposited on zeolite 13X (super cage (α) and sodalite (ß) cage structures) using the Turkevich method. Various cosmetic drugs, such as niacinamide, sulforaphane, and adenosine, were loaded under in vitro and in vivo observations. The Au-decorated zeolite nanocomposites exhibited effective cosmetic drug-loading efficiencies of 3.5 to 22.5 wt% under various conditions. For in vitro cytotoxic observations, B16F10 cells were treated with various cosmetic drugs. Niacinamide, sulforaphane, and adenosine-loaded Au-decorated zeolite nanocomposites exhibited clear cell viability of over 80%. Wrinkle improvement and a reduction in melanin content on the skin surface were observed in vivo. The adenosine delivery system exhibited an enhanced wrinkle improvement of 203% compared to 0.04 wt% of the pure adenosine system. The niacinamide- and sulforaphane-loaded Au-decorated zeolite nanocomposites decreased the skin surface melanin content by 123% and 222%, respectively, compared to 2 and 0.01 wt% of pure niacinamide and sulforaphane systems, respectively. As a result, Au-decorated zeolite nanocomposites show great potential as cosmetic drug epidermal delivery systems for both anti-aging and lightening effects.