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1.
Int J Biol Macromol ; 270(Pt 1): 132178, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38735614

ABSTRACT

In response to escalating environmental concerns and the urgent need for sustainable drug delivery systems, this study introduces biodegradable pH-responsive microcapsules synthesized from a blend of gelatin, alginate, and hyaluronic acid. Employing the coacervation process, capsules were created with a spherical shape, multicore structure, and small sizes ranging from 10 to 20 µm, which exhibit outstanding vitamin E encapsulation efficiency. With substantial incorporation of hyaluronic acid, a pH-responsive component, the resulting microcapsules displayed noteworthy swelling behavior, facilitating proficient core ingredient release at pH 5.5 and 7.4. Notably, these capsules can effectively deliver active substances to the dermal layer under specific skin conditions, revealing promising applications in topical medications and cosmetics. Furthermore, the readily biodegradable nature of the designed capsules was demonstrated through Biochemical Oxygen Demand (BOD) testing, with over 80 % of microcapsules being degraded by microorganisms after one week of incubation. This research contributes to the development of responsive microcapsules and aligns with broader environmental initiatives, offering a promising pathway to mitigate the impact of microplastics while advancing various applications.


Subject(s)
Alginates , Capsules , Delayed-Action Preparations , Drug Liberation , Gelatin , Hyaluronic Acid , Hyaluronic Acid/chemistry , Alginates/chemistry , Gelatin/chemistry , Hydrogen-Ion Concentration , Delayed-Action Preparations/chemistry , Drug Carriers/chemistry , Vitamin E/chemistry
2.
Analyst ; 149(4): 1068-1073, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-38265242

ABSTRACT

Signal amplification by reversible exchange hyperpolarization explores the chemical structure and kinetic properties of nicotinamide derivatives. N-Benzyl nicotinamide and nicotinic acid hydrazide compounds display relatively fast dissociation rates of approximately 7-8 s-1 and long proton T1 relaxation times of 5-20 s, respectively. Consequently, these substrates exhibit remarkable signal enhancements, reaching approximately 175 and 102 fold, respectively, underscoring the efficacy of the hyperpolarization technique in elucidating the behavior of these compounds.

3.
Polymers (Basel) ; 15(19)2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37836014

ABSTRACT

The typical filters that protect us from harmful components, such as toxic gases and particulate matter (PM), are made from petroleum-based materials, which need to be replaced with other environmentally friendly materials. Herein, we demonstrate a route to fabricate biodegradable and dual-functional filtration membranes that effectively remove PM and toxic gases. The membrane was integrated using two layers: (i) cellulose-based nanofibers for PM filtration and (ii) metal-organic framework (MOF)-coated cotton fabric for removal of toxic gases. Zeolitic imidazolate framework (ZIF-8) was grown from the surface of the cotton fabric by the treatment of cotton fabric with an organic precursor solution and subsequent immersion in an inorganic precursor solution. Cellulose acetate nanofibers (NFs) were deposited on the MOF-coated cotton fabric via electrospinning. At the optimal thickness of the NF layer, the quality factor of 18.8 × 10-2 Pa-1 was achieved with a filtration efficiency of 93.1%, air permeability of 19.0 cm3/cm2/s, and pressure drop of 14.2 Pa. The membrane exhibits outstanding gas adsorption efficiencies (>99%) for H2S, formaldehyde, and NH3. The resulting membrane was highly biodegradable, with a weight loss of 62.5% after 45 days under standard test conditions. The proposed strategy should provide highly sustainable material platforms for practical multifunctional membranes in personal protective equipment.

4.
Analyst ; 148(21): 5355-5360, 2023 Oct 23.
Article in English | MEDLINE | ID: mdl-37750298

ABSTRACT

This study demonstrated the potential of 50 nm PEGylated Si NPs for high-resolution in vivo29Si MR imaging, emphasizing their biocompatibility and water dispersibility. The acquisition of in vivo Si MR images using the lowest reported dose after subcutaneous and intraperitoneal administration opens new avenues for future 29Si MR studies.

5.
Carbohydr Polym ; 304: 120490, 2023 Mar 15.
Article in English | MEDLINE | ID: mdl-36641177

ABSTRACT

With an increase in the severity of environmental pollution caused by microbeads, the development of biodegradable microcapsules that can be applied in diverse fields has attracted significant attention. The degradation processes are directly related to biodegradable microcapsule creation with high stability and persistence. In this study, biodegradable microcapsules are synthesized via a complex coacervation approach using gelatin and alginate as the capsule main wall materials; additionally, enzyme-induced decomposition mechanisms are proposed by observing spectral changes in proton nuclear magnetic resonance (1H NMR) analyses. Additional analytical techniques confirm the chemical structure, morphology, and size distribution of the synthesized capsules; these uniform spherical microcapsules are 20-30 µm in size and possess a smooth surface. In addition to characterization, the microcapsules were exposed to targeted enzymes to investigate enzymatic effects using short-term and long-term degradation kinetics. Close inspection reveals that determination of the degradation rate constant of the major components in the capsule is feasible, and suggests two types of 4-stage degradation mechanisms that are enzyme-specific. These investigations demonstrate that capsule degradation can be explored in detail using 1H NMR spectroscopy to provide a viable strategy for monitoring degradation properties in the development of new biodegradable polymers.


Subject(s)
Alginates , Gelatin , Capsules/chemistry , Alginates/chemistry , Kinetics , Magnetic Resonance Spectroscopy
6.
Anal Chem ; 95(2): 907-916, 2023 01 17.
Article in English | MEDLINE | ID: mdl-36514301

ABSTRACT

29Si silica nanoparticles (SiO2 NPs) are promising magnetic resonance imaging (MRI) probes that possess advantageous properties for in vivo applications, including suitable biocompatibility, tailorable properties, and high water dispersibility. Dynamic nuclear polarization (DNP) is used to enhance 29Si MR signals via enhanced nuclear spin alignment; to date, there has been limited success employing DNP for SiO2 NPs due to the lack of endogenous electronic defects that are required for the process. To create opportunities for SiO2-based 29Si MRI probes, we synthesized variously featured SiO2 NPs with selective 29Si isotope enrichment on homogeneous and core@shell structures (shell thickness: 10 nm, core size: 40 nm), and identified the critical factors for optimal DNP signal enhancement as well as the effective hyperpolarization depth when using an exogenous radical. Based on the synthetic design, this critical factor is the proportion of 29Si in the shell layer regardless of core enrichment. Furthermore, the effective depth of hyperpolarization is less than 10 nm between the surface and core, which demonstrates an approximately 40% elongated diffusion length for the shell-enriched NPs compared to the natural abundance NPs. This improved regulation of surface properties facilitates the development of isotopically enriched SiO2 NPs as hyperpolarized contrast agents for in vivo MRI.


Subject(s)
Nanoparticles , Silicon Dioxide , Silicon Dioxide/chemistry , Nanoparticles/chemistry , Contrast Media/chemistry , Magnetic Resonance Imaging , Magnetic Resonance Spectroscopy
7.
J Clin Med ; 11(23)2022 Nov 30.
Article in English | MEDLINE | ID: mdl-36498707

ABSTRACT

Psoriasis is a chronic inflammatory skin disease associated with various factors. Recently, alterations in the gut and skin microbiomes have been shown to interact with host immunity, affect skin barrier function, as well as development and progression of psoriasis. We aimed to analyze the microbiota of the scalp of patients with psoriasis and determine the characteristics of the microbiome according to disease severity. We investigated the scalp microbiome of 39 patients with psoriasis scalp lesions and a total of 47 samples were analyzed. The patients were divided into mild, moderate, and severe groups according to the European recommendations for scalp psoriasis. For bacterial identification, we utilized the SILVA database targeting the V3 region of the 16 S rRNA gene. The mean Shannon index escalated along with disease severity, and the diversity of the scalp microbiome tended to increase with disease severity (R = 0.37, p < 0.01). The relative abundance of Pseudomonas was increased in severe scalp psoriasis (0.49 ± 0.22) compared to the mild group (0.07 ± 0.03, p = 0.029), and Diaphorobacter was enriched in the mild group (0.76 ± 0.16%) compared to the severe group (0.44 ± 0.22, p < 0.001). We identified that increased diversity of the scalp microbiome and the relative abundance of Pseudomonas are associated with the severity of scalp psoriasis.

8.
Analyst ; 147(24): 5607-5612, 2022 Dec 05.
Article in English | MEDLINE | ID: mdl-36377709

ABSTRACT

The embedding of radicals at different locations within core@shell silica nanoparticles contributes to enhanced polarization capability and can be self-polarized without adding external radicals. With grafting the radical source homogenously inside of the nanoparticles, a significant 29Si hyperpolarization signal enhancement of 49.4 was obtained.


Subject(s)
Nanoparticles , Silicon Dioxide , Silicon Dioxide/chemistry , Magnetic Resonance Spectroscopy/methods , Magnetic Resonance Imaging/methods , Nanoparticles/chemistry
9.
Biomater Sci ; 10(13): 3540-3546, 2022 Jun 28.
Article in English | MEDLINE | ID: mdl-35611753

ABSTRACT

Covalent surface modification of silica nanoparticles (SNPs) offers great potential for the development of multimodal nanomaterials for biomedical applications. Herein, we report the synthesis of covalently conjugated bifunctional SNPs and their application to in vivo multimodal imaging. Bis(methallyl)silane 15 with cyclopropene and maleimide, designed as a stable bifunctional linker, was efficiently synthesized by traceless Staudiger ligation, and subsequently introduced onto the surface of monodispersed SNPs via Sc(OTf)3-catalyzed siloxane formation. The bifunctional linker-grafted SNP 20 underwent both thiol-conjugated addition and tetrazine cycloaddition in one pot. Finally, positron emission tomography/computed tomography and fluorescence imaging study of dual functional SNP [125I]28 labeled with NIR dye and 125I isotope showed a prolonged circulation in mice, which is conducive to the systemic delivery of therapeutics.


Subject(s)
Nanoparticles , Silicon Dioxide , Animals , Iodine Radioisotopes , Mice , Optical Imaging
10.
J Mater Chem B ; 10(10): 1561-1570, 2022 03 09.
Article in English | MEDLINE | ID: mdl-35129191

ABSTRACT

Tannic acid (TA) not only prevents drug carriers from sticking to the glycocalyx layer of vascular endothelial cells but also has anti-cancer properties, thereby improving drug delivery efficiency in cancer treatment. This study proposes a TANNylated nanovesicle-based cancer treatment approach by utilizing the aforementioned advantages of TA. We fabricated cancer cell-targeting BC71 peptide-conjugated TANNylated nanovesicles (TANVBC71) by covalently bonding the TA derivative and BC71 (cyclo[ßA-kRK(3-maleimidopropionyl)-D-(D-2-naphthyl)]) with thiol-modified phospholipids through the thiol-maleimide reaction. We demonstrated that TANVBC71 was absorbed faster in high amounts by cancer cells than nanovesicles owing to its high affinity for the epidermal growth factor receptor and extracellular matrix components that are driven by van der Waals attraction as well as hydrogen bonding and hydrophobic interactions in a complex manner. These complex attractions of TANVBC71 for cancer cells led to the effective induction of cancer cell apoptosis. The findings obtained in this study highlight that the TANVBC71 system has the potential for intelligent high-efficacy cancer cell drug delivery.


Subject(s)
Endothelial Cells , Polyphenols , Apoptosis , Drug Carriers/chemistry , Polyphenols/pharmacology , Sulfhydryl Compounds
11.
Sci Total Environ ; 820: 153327, 2022 May 10.
Article in English | MEDLINE | ID: mdl-35066050

ABSTRACT

Soot is one of the main harmful emissions of diesel engines that is mainly generated in the reacting fuel jet of diesel injection. Over 99% of the engine-out soot can be filtered by a diesel particulate filter (DPF). However, when the soot load of the DPF is high, a regeneration process that oxidizes the accumulated soot reduces fuel economy. A real-time soot estimation model can contribute to real-time feedback soot control under transient conditions to minimize the engine-out soot emission and frequency of DPF regeneration. A zero-dimensional engine-out soot estimation model for a diesel engine is developed in this study. The semi-empirical soot model considers both the formation and oxidation of soot. In the model, soot formation was correlated with the cross-sectional average equivalence ratio at the lift-off length of the fuel spray. The equivalence ratio at the lift-off length is an indicator of how much air and vaporized fuel are mixed as the fuel reaches the reaction zone. The mass of the injected fuel and combustion duration were also correlated with soot formation. The Nagle and Strickland-Constable mechanism, which calculates the soot oxidation rate was correlated with the soot oxidation in this study. The results of the soot estimation showed an R2 of 0.901 and root mean square error of 10.8 mg/m3 for steady-state experimental cases. The engine-out soot model was also combined with the in-cylinder pressure model proposed by the authors, and validated through the transient Worldwide Harmonized Light Vehicles Test Cycle (WLTC) mode. The estimates agreed with the measured soot, with an accumulated soot error of approximately 6% during the WLTC, even without using an in-cylinder pressure sensor. The soot model developed in this study can help minimize tailpipe-out soot emissions and improve fuel economy by influencing the real-time feedback control during transient and frequent DPF regeneration.

12.
J Med Chem ; 65(1): 386-408, 2022 01 13.
Article in English | MEDLINE | ID: mdl-34982557

ABSTRACT

The serine protease inhibitor Rv3364c of Mycobacterium tuberculosis (MTB) is highly expressed in cells during MTB exposure. In this study, we showed that the 12WLVSKF17 motif of Rv3364c interacts with the BAR domain of SNX9 and inhibits endosome trafficking to interact with p47phox, thereby suppressing TLR4 inflammatory signaling in macrophages. Derived from the structure of this Rv3364c peptide motif, 2,4-diamino-6-(4-tert-butylphenyl)-1,3,5-trazine, DATPT as a 12WLVSKF17 peptide-mimetic small molecule has been identified. DATPT can block the SNX9-p47phox interaction in the endosome and suppress reactive oxygen species and inflammatory cytokine production; it demonstrated significant therapeutic effects in a mouse model of cecal ligation and puncture-induced sepsis. DATPT has considerably improved potency, with an IC50 500-fold (in vitro) or 2000-fold (in vivo) lower than that of the 12WLVSKF17 peptide. Furthermore, DATPT shows potent antibacterial activities by reduction in ATP production and leakage of intracellular ATP out of bacteria. These results provide evidence for peptide-derived small molecule DATPT with anti-inflammatory and antibacterial functions for the treatment of sepsis.


Subject(s)
Anti-Bacterial Agents/pharmacology , Mycobacterium tuberculosis/chemistry , Sepsis/drug therapy , Small Molecule Libraries , Sorting Nexins/drug effects , Adenosine Triphosphate/metabolism , Animals , Anti-Bacterial Agents/chemistry , Cytokines/antagonists & inhibitors , Endosomes/drug effects , High-Throughput Screening Assays , Mice , Mice, Knockout , Peptide Fragments/drug effects , Reactive Oxygen Species , Sepsis/microbiology , Serine Proteinase Inhibitors/chemistry , Serine Proteinase Inhibitors/pharmacology , Signal Transduction/drug effects , Sorting Nexins/chemistry
13.
ACS Appl Mater Interfaces ; 13(48): 56923-56930, 2021 Dec 08.
Article in English | MEDLINE | ID: mdl-34793118

ABSTRACT

Silicon particles have garnered attention as promising biomedical probes for hyperpolarized 29Si magnetic resonance imaging and spectroscopy. However, due to the limited levels of hyperpolarization for nanosized silicon particles, microscale silicon particles have primarily been the focus of dynamic nuclear polarization (DNP) applications, including in vivo magnetic resonance imaging (MRI). To address these current challenges, we developed a facile synthetic method for partially 29Si-enriched porous silicon nanoparticles (NPs) (160 nm) and examined their usability in hyperpolarized 29Si MRI agents with enhanced signals in spectroscopy and imaging. Hyperpolarization characteristics, such as the build-up constant, the depolarization time (T1), and the overall enhancement of the 29Si-enriched silicon NPs (10 and 15%), were thoroughly investigated and compared with those of a naturally abundant NP (4.7%). During optimal DNP conditions, the 15% enriched silicon NPs showed more than 16-fold higher enhancements─far beyond the enrichment ratio─than the naturally abundant sample, further improving the signal-to-noise ratio in in vivo 29Si MRI. The 29Si-enriched porous silicon NPs used in this work are potentially capable to serve as drug-delivery vehicles in addition to hyperpolarized 29Si in vivo, further enabling their potential future applicability as a theragnostic platform.


Subject(s)
Biomimetic Materials/chemistry , Contrast Media/chemistry , Magnetic Resonance Imaging , Nanoparticles/chemistry , Phantom Limb/diagnostic imaging , Silicon/chemistry , Animals , Biomimetic Materials/administration & dosage , Biomimetic Materials/chemical synthesis , Contrast Media/administration & dosage , Contrast Media/chemical synthesis , Isotopes , Male , Materials Testing , Mice , Mice, Inbred BALB C , Mice, Nude , Nanoparticles/administration & dosage , Particle Size , Porosity , Silicon/administration & dosage
14.
J Clin Med ; 10(17)2021 Aug 31.
Article in English | MEDLINE | ID: mdl-34501405

ABSTRACT

Adult height is linked to the risk of several diseases, but its association with vitiligo has not been established. This study aimed to investigate the relationship between adult height and vitiligo incidence. Korean nationwide claims data from 15,980,754 individuals (20 years of age or older) who received a health checkup during the period 2005-2008, were examined. Subjects were categorized into age- and gender-specific height quintiles. Participants were followed until vitiligo diagnosis or until the end of 2015. The Cox proportional-hazards model for cumulative risk was computed for height categories. During the follow-up period, 29,196 cases (136,020,214 person-years) of newly diagnosed vitiligo were reported. A positive association was found between height and risk of vitiligo in which the hazard ratio between the highest and lowest quintiles of height was 1.36 (95% confidence interval: 1.31-1.42). While more diverse cohort studies are needed, our findings suggest that taller stature increases the risk of vitiligo.

15.
Molecules ; 26(9)2021 May 08.
Article in English | MEDLINE | ID: mdl-34066676

ABSTRACT

Microcolumns have a stacked structure composed of an electron emitter, electron lens (source lens), einzel lens, and a deflector manufactured using a micro electro-mechanical system process. The electrons emitted from the tungsten field emitter mostly pass through the aperture holes. However, other electrons fail to pass through because of collisions around the aperture hole. We used Raman scattering measurements and X-ray photoelectron spectroscopy analyses to investigate the influence of electron beam bombardment on a Si electron lens irradiated by acceleration voltages of 0, 20, and 30 keV. We confirmed that the crystallinity was degraded, and carbon-related contamination was detected at the surface and edge of the aperture hole of the Si electron lens after electron bombardment for 24 h. Carbon-related contamination on the surface of the Si electron lens was verified by analyzing the Raman spectra of the carbon-deposited Si substrate using DC sputtering and a carbon rod sample. We report the crystallinity and the origin of the carbon-related contamination of electron Si lenses after electron beam bombardment by non-destructive Raman scattering and XPS analysis methods.

16.
J Dermatol ; 48(7): 1062-1066, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33961305

ABSTRACT

Metabolic syndrome (MetS) is characterized by insulin resistance, high blood pressure/sugar, dyslipidemia, and obesity. Whether MetS and its components affect the development of Behçet's disease (BD) remains unclear. This study was performed to investigate the associations between metabolic syndrome and risk of BD using nationwide population data. We conducted a retrospective cohort study of 10 505 818 Korean subjects who received health checkups in 2009-2012. Patients were classified into a MetS and its components group and were followed-up until 2016 for new-onset BD. A Cox proportional hazards model was used to assess the independent or synergistic effects of MetS and its components on the risk of incident BD. Compared to subjects without MetS components, the hazard ratio (HR) for development of BD in patients with MetS was 0.874 (95% confidence interval [CI]: 0.819-0.933) and this association was more prominent when all components of MetS were present (HR = 0.675, 95% CI = 0.571-0.798). Subjects with low high density lipoprotein (HDL) has a significantly increased risk of the development of BD (HR = 1.51, 95% CI = 1.4-1.594) compared to controls. This study showed that the incidence of Behçet's disease was reduced in subjects with MetS. Moreover, the presence of MetS components, with the exception of HDL, was negatively related to the development of BD.


Subject(s)
Behcet Syndrome , Hypertension , Metabolic Syndrome , Humans , Incidence , Retrospective Studies , Risk Factors
17.
Chem Commun (Camb) ; 56(95): 15000-15003, 2020 Dec 07.
Article in English | MEDLINE | ID: mdl-33185204

ABSTRACT

The decarboxylation reaction of phenylglyoxylic acid with hydrogen peroxide is studied by real-time hyperpolarized carbon-13 nuclear magnetic resonance (13C NMR) spectroscopy at room temperature. A non-observable reaction intermediate is identified using blind selective saturation pulses in the expected chemical shift range, thereby revealing information on the reaction mechanism.

18.
J Colloid Interface Sci ; 561: 318-326, 2020 Mar 01.
Article in English | MEDLINE | ID: mdl-31740134

ABSTRACT

We report a facile, but robust approach to fabricate structurally stable giant unilamellar vesicles (GUVs), on which a 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayer membrane was made rigid by introducing amphiphilic block polymers. Particularly, we found that lateral co-assembly of an amphiphilic triblock copolymer (ATC) structured with a hydrophobic middle block and long molecular weight (20 K g/mol) hydrophilic end blocks remarkably enhanced the stretching modulus (k) of GUVs. When the membrane composition was optimized, the k value of ATC-hybridized GUVs increased to 6.2 × 108 Pa, which was approximately 10-fold higher than that of DPPC GUVs, thus leading to a much longer half-life. Moreover, we demonstrated that our ATC-hybridized GUVs enabled development of a fascinating vesicular model, which shows great potential as a structurally stable cell membrane mimic.


Subject(s)
1,2-Dipalmitoylphosphatidylcholine/analogs & derivatives , Lipid Bilayers/chemistry , Liposomes/chemistry , Polymers/chemistry , Unilamellar Liposomes/chemistry , 1,2-Dipalmitoylphosphatidylcholine/chemistry , Hydrophobic and Hydrophilic Interactions
19.
Soft Matter ; 15(40): 8051-8058, 2019 Oct 28.
Article in English | MEDLINE | ID: mdl-31549697

ABSTRACT

In this study, we measured the force of electrostatic interactions between poly(methyl methacrylate) (PMMA) particles dispersed in organic solvent mixtures of cyclohexyl bromide (CHB) and n-decane. Optical laser tweezers were employed to directly measure interactive forces between paired PMMA particles in a CHB medium that contained n-decane in various volume ratios. CHB, having a moderate dielectric constant, provided an environment with a high charge storage capacity. The addition of n-decane lowered the effective refractive index of the medium, which increased the optical trapping efficiency. We also fabricated microscope flow cells with a commonly used UV-curable adhesive and quantified the effects of dissolved adhesive compounds through interactive force measurements and nuclear magnetic resonance analysis. In addition, we studied the impact of CHB dissociation into H+ and Br- ions, which could screen electrostatic interactions.

20.
Diabetes Metab ; 45(1): 32-38, 2019 01.
Article in English | MEDLINE | ID: mdl-29249611

ABSTRACT

AIM: As the associations between actinic keratosis (AK) and diabetes complications in patients with diabetes mellitus (DM) have never been investigated, this study aimed to evaluate any such associations in patients with DM. METHODS: This retrospective cohort study analyzed clinical data for DM patients aged>40 years who had undergone the health examination recommended by the South Korea National Health Insurance Program between 2009 and 2012 (n=2,056,580). All of these patients were classified according to the presence of diabetic retinopathy (DR), end-stage renal disease (ESRD) and history of DVD; myocardial infarction, stroke, transient ischaemic attacks. Newly diagnosed AK was identified using claims data from baseline to the date of diagnosis or 31 December 2015, whichever came first. RESULTS: Of the 2,056,580 patients with DM, 6404 (0.31%) developed AK. Those patients in the DR, ESRD and CVD groups were more likely to be diagnosed with AK (P<0.001, by log-rank test). After adjusting for age and gender, the risks for AK were significantly higher in the DR, ESRD and CVD groups: HR (95% CI): 1.29 (1.21-1.39), HR: 4.24 (3.28-5.47) and HR: 1.22 (1.13-1.31), respectively. CONCLUSION: This study has revealed that the incidence of AK is higher in diabetes patients with ocular, renal and cardiovascular complications.


Subject(s)
Diabetic Cardiomyopathies/epidemiology , Diabetic Nephropathies/epidemiology , Diabetic Retinopathy/epidemiology , Keratosis, Actinic/epidemiology , Adult , Aged , Comorbidity , Female , Humans , Incidence , Male , Middle Aged , Republic of Korea , Retrospective Studies
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