Prevalence of thyroid diffuse goiter and its association with body mass index and the presence of cysts and nodules in children and adolescents: the Fukushima Health Management Survey.

The main cause of diffuse thyroid goiter is autoimmune chronic thyroiditis, otherwise known as Hashimoto's thyroiditis. Thyroid hormones play pivotal roles in growth and development during childhood. However, the prevalence of diffuse goiter and the relationships between diffuse goiter, thyroid volume, cysts and nodules, and anthropometric measurements in children are not well known. Among 789,459 participants who participated in thyroid ultrasound examinations, 320,206 participants (male: 161,728; female: 158,478) aged 1-23 years were analyzed. Logistic regression analyses were conducted to calculate the odds ratios of the standard deviation score of body mass index (BMI-SDS), the SDS of bilateral width multiplied thickness area (BWTAR-SDS) as a provisional determination of thyroid volume, and the presence of nodules or cysts for positive diffuse goiter compared with negative diffuse goiter after correction for sex and age. The prevalence of diffuse goiter increased in a female-dominant manner with aging. Compared with the absence of diffuse goiter, the age- and sex-adjusted odds ratios (95% confidence intervals) for BMI-SDS (1 SD), BWTAR-SDS (1 SD), cysts, and nodules were 1.24 (1.21-1.27), 3.21 (3.13-3.29), 0.53 (0.50-0.58), and 1.38 (1.17-1.64), respectively. The odds ratios of nodules for positive diffuse goiter were 4.18 (1.08-16.08), 1.76 (1.01-3.07), 1.80 (1.32-2.45), and 1.34 (1.08-1.67) in the age groups 1-7, 8-11, 12-15, and 16-23 years, respectively. The age-dependent increase in the prevalence of diffuse goiter was independently associated with increased BMI and positive prevalence of nodules in young individuals.

Impact of the TRPV2 Inhibitor on Advanced Heart Failure in Patients with Muscular Dystrophy: Exploratory Study of Biomarkers Related to the Efficacy of Tranilast.

Cardiomyopathy is the leading cause of death in patients with muscular dystrophy (MD). Tranilast, a widely used anti-allergic drug, has displayed inhibitory activity against the transient receptor potential cation channel subfamily V member 2 and improved cardiac function in MD patients. To identify urinary biomarkers that assess improved cardiac function after tranilast administration, we performed a urinary metabolomic study focused on oxidative fatty acids. Accompanying the clinical trial of tranilast, urine specimens were collected over 24 weeks from MD patients with advanced heart failure. Urinary levels of tetranor-PGDM (tetranor-prostaglandin D metabolite), a metabolite of prostaglandin D2, significantly decreased 12 weeks after tranilast administration and were correlated with BNP. These results suggest that prostaglandin-mediated inflammation, which increases with the pathological progression of heart failure in MD patients, was attenuated. Urinary prostaglandin E3 (PGE3) levels significantly increased 4 weeks after tranilast administration. There were positive correlations between the urinary levels of PGE3 and 8-hydroxy-2'-deoxyguanosine, an oxidative stress marker. High PGE3 levels may have a protective effect against cardiomyopathy in MD patients with high oxidative stress. Although further validation studies are necessary, urinary tetranor-PGDM and PGE3 levels may help the current understanding of the extent of advanced heart failure in patients with MD after tranilast administration.

Biofilm formation of Staphylococcus epidermidis imaged using atmospheric scanning electron microscopy.

Staphylococcus epidermidis are gram-positive bacteria that form a biofilm around implanted devices and develop an infection into a chronic state. Recently, it has been revealed that microvesicles have important roles in biofilm formation and intercellular communication among bacteria. However, biofilm formation of Staphylococcus epidermidis, and its relation to microvesicle secretion, is poorly understood because of the difficulty required to preserve the delicate water-rich morphology of biofilm for high-resolution observations. Here, we successfully imaged the microvesicles secreted from Staphylococcus epidermidis and the subsequent process of their integration into biofilm using liquid-phase imaging using atmospheric scanning electron microscopy (ASEM). In the biofilm, cells were connected by nanotube-like structures attached by microvesicles, and surrounded by extracellular polymeric substances. Cells cultured in the ASEM specimen holder were aldehyde-fixed and stained using positively charged nanogold labelling and/or using National Center for Microscopy and Imaging Research method. The samples immersed in aqueous radical scavenger glucose buffer were imaged by the inverted SEM of ASEM. Information regarding the morphologies of microvesicles, nanotube-like fibrils, and biofilm formed by Staphylococcus epidermidis is expected to be useful to elucidate the biological mechanism of biofilm formation and to develop a medicine against biofilms and their associated infections.

Biophysical Parameters of the Sec14 Phospholipid Exchange Cycle.

Sec14, the major yeast phosphatidylcholine (PC)/phosphatidylinositol (PI) transfer protein (PITP), coordinates PC and PI metabolism to facilitate an appropriate and essential lipid signaling environment for membrane trafficking from trans-Golgi membranes. The Sec14 PI/PC exchange cycle is essential for its essential biological activity, but fundamental aspects of how this PITP executes its lipid transfer cycle remain unknown. To address some of these outstanding issues, we applied time-resolved small-angle neutron scattering for the determination of protein-mediated intervesicular movement of deuterated and hydrogenated phospholipids in vitro. Quantitative analysis by small-angle neutron scattering revealed that Sec14 PI- and PC-exchange activities were sensitive to both the lipid composition and curvature of membranes. Moreover, we report that these two parameters regulate lipid exchange activity via distinct mechanisms. Increased membrane curvature promoted both membrane binding and lipid exchange properties of Sec14, indicating that this PITP preferentially acts on the membrane site with a convexly curved face. This biophysical property likely constitutes part of a mechanism by which spatial specificity of Sec14 function is determined in cells. Finally, wild-type Sec14, but not a mixture of Sec14 proteins specifically deficient in either PC- or PI-binding activity, was able to effect a net transfer of PI or PC down opposing concentration gradients in vitro.

Morphological study of efficacy of clarithromycin-loaded nanocarriers for treatment of biofilm infection disease.

In this study, we developed a drug delivery system (DDS) using polymeric nanocarriers for the treatment of biofilm infection disease. Clarithromycin (CAM)-encapsulated and chitosan (CS) modified polymeric nanoparticles (NPs) were prepared using a polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) (Sol) and poly-(DL-lactide-co-glycolide), respectively. To understand the availability of the prepared NPs, we made morphological observations of the antibacterial activity derived from the NPs toward the bacterial cells within the biofilm using scanning electron microscopy and transmission electron microscopy measurements. These results revealed different antibacterial activities for the two types of drug carriers. In the case of CAM-encapsulated + CS-modified Sol micelles treatment, NPs can exert their antibacterial activity not only by the surfactant, CAM and CS effects but also by intrusion into the bacterial cells. Thereby, CAM-encapsulated + CS-modified Sol micelles had a higher antibacterial activity. The morphological information is useful to design suitable NPs for the treatment against biofilm infections.

Prostacyclin prevents pericyte loss and demyelination induced by lysophosphatidylcholine in the central nervous system.

Pericytes play pivotal roles in physiological and pathophysiological conditions in the central nervous system. As pericytes prevent vascular leakage, they can halt neuronal damage stemming from a compromised blood-brain barrier. Therefore, pericytes may be a good target for the treatment of neurodegenerative disorders, although evidence is lacking. In this study, we show that prostacyclin attenuates lysophosphatidylcholine (LPC)-mediated vascular dysfunction through pericyte protection in the adult mouse spinal cord. LPC decreased the number of pericytes in an in vitro blood-brain barrier model, and this decrease was prevented by iloprost treatment, a prostacyclin analog. Intrathecal administration of iloprost attenuated vascular barrier disruption after LPC injection in the mouse spinal cord. Furthermore, iloprost treatment diminished demyelination and motor function deficits in mice injected with LPC. These results support the notion that prostacyclin acts on pericytes to maintain vascular barrier integrity.

Influence of oxygen on nitrogen-doped carbon nanofiber growth directly on nichrome foil.

The synthesis of various nitrogen-doped (N-doped) carbon nanostructures has been significantly explored as an alternative material for energy storage and metal-free catalytic applications. Here, we reveal a direct growth technique of N-doped carbon nanofibers (CNFs) on flexible nichrome (NiCr) foil using melamine as a solid precursor. Highly reactive Cr plays a critical role in the nanofiber growth process on the metal alloy foil in an atmospheric pressure chemical vapor deposition (APCVD) process. Oxidation of Cr occurs in the presence of oxygen impurities, where Ni nanoparticles are formed on the surface and assist the growth of nanofibers. Energy-dispersive x-ray spectroscopy (EDXS) and x-ray photoelectron spectroscopy (XPS) clearly show the transformation process of the NiCr foil surface with annealing in the presence of oxygen impurities. The structural change of NiCr foil assists one-dimensional (1D) CNF growth, rather than the lateral two-dimensional (2D) growth. The incorporation of distinctive graphitic and pyridinic nitrogen in the graphene lattice are observed in the synthesized nanofiber, owing to better nitrogen solubility. Our finding shows an effective approach for the synthesis of highly N-doped carbon nanostructures directly on Cr-based metal alloys for various applications.

Electron microscopy of Staphylococcus epidermidis fibril and biofilm formation using image-enhancing ionic liquid.

We established an optimized biofilm observation method using a hydrophilic ionic liquid (IL), 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]). In the present study, a biofilm was formed by Staphylococcus epidermidis. Using field emission (FE) scanning electron microscopy (SEM) and transmission electron microscopy (TEM), the colonization of assemblages formed by microbial cells was observed as a function of the cultivation time. FE-TEM analysis revealed that the fibril comprises three types of protein. In addition, the ultrastructure of each protein monomer was visualized. It was expected that the curly-structured protein plays an important role in extension during fibril formation. Compared to the conventional sample preparation method for electron microscopy, a fine structure was easily obtained by the present method using IL. This observation technique can provide valuable information to characterize the ultrastructure of the fibril and biofilm that has not been revealed till date. Furthermore, these findings of the molecular architecture of the fibril and the colonization behavior of microbial cells during biofilm formation are useful for the development of antibacterial drugs and microbial utilization.

Quality Evaluation of Gentamicin Sulfate Reference Standards in Japanese Pharmacopoeia Using Hydrophilic Interaction Chromatography Combined With Tandem Mass Spectrometry.

BACKGROUND: Through the recent development of analytical technology, antibiotics quantification in the Japanese Pharmacopoeia (JP) has changed from traditional microbiological assays to physicochemical methods with high specificity and precision. However, for several multicomponent antibiotics without typical UV absorption, potency cannot be directly determined using instrumental methods such as high-performance liquid chromatography; therefore, traditional microbiological assays are still used. Gentamicin sulfate (GmS), which consists of three major components, C1, C1a, and C2, is such a typical antibiotic, and its antimicrobial potency continues to be assayed using microbiological methods in JP monographs. Introduction of a physicochemical assay for GmS is needed to help ensure its quality and quantity. OBJECTIVE: This study aimed to develop quality control measures for GmS that could be complementary to quantitative assays and purity tests specified in the JP. METHODS: For each gentamicin C component (C1, C2, and C1a), theoretical potencies were determined based on the quantitative relationship between purity and potency, as measured by quantitative 1H NMR and microbiological assays, respectively. Two lots of the JP reference standard (RS) were used as test samples, with the contents of each component and impurity (sisomicin and garamine) being determined using hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). RESULTS: The ratios of theoretical potency for C1, C2, and C1a were 1.00, 1.21, and 1.80, respectively. The potencies of the GmS JP RSs, which were estimated based on the contents and theoretical potency of each C component, corresponded well with those determined through microbiological assays. Marked differences in impurities (%) between the two RS lots were highlighted by quantifying sisomicin and garamine. CONCLUSIONS: The developed analytical procedure enabled the characterization of two different JP RSs in terms of content ratio, potencies, and impurities. HIGHLIGHTS: Novel analytical procedures useful for routine quality control of GmS were developed using HILIC-MS/MS.

Ultrasonography-based reference values for the cross-sectional area of the thyroid gland in children and adolescents: The Fukushima Health Management Survey.

We previously described the thyroid volume, which was calculated by measuring the thyroid width, thickness, and longitudinal length using ultrasonography, in children and adolescents. We have proposed a simplified method for quantitatively assessing the thyroid size, to overcome the inaccuracy and challenges in measuring the longitudinal length of the thyroid. Based on measurements of 317,847 (girls: 156,913, boys: 160,934) children and adolescents, we calculated sex-specific means and standard deviations of thyroid width and thickness, and of the cross-sectional area computed by multiplying them, for every age and 0.1 m2 of body surface area, after ensuring normal distribution with Box-Cox transformation. Multivariate regression analysis revealed that female sex, age, and body surface area were independently associated with areas of each thyroid lobe. Our novel method may be useful in quantitatively assessing the thyroid size, and appropriately diagnosing pathological conditions, such as hypoplasia, atrophy, and enlargement of the thyroid gland, in children and adolescents.

Screening and quantification of undeclared PGF2α analogs in eyelash-enhancing cosmetic serums using LC-MS/MS.

In recent years, cosmetics deemed equivalent to pharmaceutical products containing prostaglandin F2α (PGF2α) analogs have been distributed overseas in the form of eyelash serums that can be purchased via the internet. The purpose of this study was to investigate the presence or absence of PGF2α analogs in eyelash serums procured in Japan via the internet to elucidate the actual composition. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurement system was developed for the determination of 14 PGF2α analogs in cosmetic serums. In total, 64 eyelash serum samples were purchased from 34 websites. After pretreatment, eyelash serum samples were screened for PGF2α analogs using the LC-MS/MS system. Products containing PGF2α analogs were subjected to quantification of these compounds. Of the 64 products, four were found to contain bimatoprost, among which, three did not indicate their contents on their package labels. In contrast, no samples were found to contain latanoprost, travoprost, or tafluprost, which are prescribed for glaucoma treatment. Additionally, eight products contained other PGF2α analogs, which have not been used as pharmaceuticals. The ease of access to cosmetic serums containing PGF2α analogs via online purchases presents a risk of serious side effects, particularly when consumers are not informed of their contents on the packages. This issue requires serious consideration to avoid the incorporation of pharmaceutical substances into cosmetic products.

Preparation of silver-decorated Soluplus® nanoparticles and antibacterial activity towards S. epidermidis biofilms as characterized by STEM-CL spectroscopy.

Biofilm infections present a serious problem because antibacterial drugs are not effective against mature biofilms or biofilms formed by drug-resistant bacteria. To address this issue, we developed a drug delivery system based on metal-decorated polymeric particles. Polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) is an amphiphilic polymer used in biomedical formulations, while silver nanoparticles are widely acknowledged to have high antibacterial activity. We prepared silver-decorated Soluplus® micelle nanoparticles with high antibacterial activity using the emulsion solvent diffusion method. Decoration of Soluplus® micelles with silver nanoparticles was found to increase their antibacterial activity. Scanning transmission electron microscopy-cathodoluminescence (STEM-CL) spectroscopy allows imaging of the spatial distribution of labeled targets and the chemical identification of materials. However, STEM-CL spectroscopy of fragile polymer materials is challenging. We optimized the STEM-CL spectroscopy technique to determine the distribution of silver nanoparticles in Soluplus® micelles. Additionally, the surface plasmon properties of the silver nanoparticles were successfully characterized without deactivation. The developed silver-decorated Soluplus® nanoparticles were effective against biofilm infections and have the potential to be applied for other biofilm-related diseases. Additionally, the optimized STEM-CL spectroscopy technique is expected to contribute to the analysis and imaging of fragile polymer materials, as well as other soft materials such as cells and tissues.

Discovery of anti-inflammatory physiological peptides that promote tissue repair by reinforcing epithelial barrier formation.

Epithelial barriers that prevent dehydration and pathogen invasion are established by tight junctions (TJs), and their disruption leads to various inflammatory diseases and tissue destruction. However, a therapeutic strategy to overcome TJ disruption in diseases has not been established because of the lack of clinically applicable TJ-inducing molecules. Here, we found TJ-inducing peptides (JIPs) in mice and humans that corresponded to 35 to 42 residue peptides of the C terminus of alpha 1-antitrypsin (A1AT), an acute-phase anti-inflammatory protein. JIPs were inserted into the plasma membrane of epithelial cells, which promoted TJ formation by directly activating the heterotrimeric G protein G13. In a mouse intestinal epithelial injury model established by dextran sodium sulfate, mouse or human JIP administration restored TJ integrity and strongly prevented colitis. Our study has revealed TJ-inducing anti-inflammatory physiological peptides that play a critical role in tissue repair and proposes a previously unidentified therapeutic strategy for TJ-disrupted diseases.

Salivary alpha-amylase levels and big five personality factors in adults.

OBJECTIVES: Salivary alpha-amylase (sAA) has been utilized as a non-invasive measure of sympathoadrenal medullary (SAM) activation. Little is known regarding the relationship between personality inventories and baseline sAA. This study was designed to examine the relationships between the scores of big five inventory (BFI) factors, age, and sAA in adults (aged twenty to seventy years old). METHODS: We assessed 97 participants' BFI scores and sAA. The correlations between the BFI factor scores and sAA were examined. RESULTS: We observed (1) a positive correlation between Neuroticism and sAA, and a negative correlation between Agreeableness and sAA and (2) a positive correlation between age and sAA. These correlations between BFI scores and sAA remained significant after controlling for age. After controlling for age, all BFI factors except Conscientiousness were related to sAA. CONCLUSIONS: Subjects with high Neuroticism and low Extraversion, Agreeableness and Openness may have high sAA. sAA has been demonstrated to be useful for examining the relationship between adrenergic activity and personality, in a non-invasive manner.

Stress hormones predict hyperbolic time-discount rates six months later in adults.

OBJECTIVES: Stress hormones have been associated with temporal discounting. Although time-discount rate is shown to be stable over a long term, no study to date examines whether individual differences in stress hormones could predict individuals' time-discount rates in the relatively distant future (e.g., six month later), which is of interest in neuroeconomics of stress-addiction association. METHODS: We assessed 87 participants' salivary stress hormone (cortisol, cortisone, and alpha-amylase) levels and hyperbolic discounting of delayed rewards consisting of three magnitudes, at the time-interval of six months. For salivary steroid assays, we employed a liquid chromatography/ mass spectroscopy (LC/MS) method. The correlations between the stress hormone levels and time-discount rates were examined. RESULTS: We observed that salivary alpha-amylase (sAA) levels were negatively associated with time-discount rates in never-smokers. Notably, salivary levels of stress steroids (i.e., cortisol and cortisone) negatively and positively related to time-discount rates in men and women, respectively, in never-smokers. Ever-smokers' discount rates were not predicted from these stress hormone levels. CONCLUSIONS: Individual differences in stress hormone levels predict impulsivity in temporal discounting in the future. There are sex differences in the effect of stress steroids on temporal discounting; while there was no sex defference in the relationship between sAA and temporal discounting.

[Accuracy of judgment about others' cooperative behavior: effects of attractiveness and facial expressiveness].

Cooperation in interdependent relationships is based on reciprocity in repeated interactions. However, cooperation in one-shot relationships cannot be explained by reciprocity. Frank, Gilovich, & Regan (1993) argued that cooperative behavior in one-shot interactions can be adaptive if cooperators displayed particular signals and people were able to distinguish cooperators from non-cooperators by decoding these signals. We argue that attractiveness and facial expressiveness are signals of cooperators. We conducted an experiment to examine if these signals influence the detection accuracy of cooperative behavior. Our participants (blind to the target's behavior in a Trust Game) viewed 30-seconds video-clips. Each video-clip was comprised of a cooperator and a non-cooperator in a Trust Game. The participants judged which one of the pair gave more money to the other participant. We found that participants were able to detect cooperators with a higher accuracy than chance. Furthermore, participants rated male non-cooperators as more attractive than male cooperators, and rated cooperators more expressive than non-cooperators. Further analyses showed that attractiveness inhibited detection accuracy while facial expressiveness fostered it.

A Short Peptide Derived from the ZorO Toxin Functions as an Effective Antimicrobial.

Antimicrobial peptides are potential molecules for the development of novel antibiotic agents. The ZorO toxin of a type I toxin-antitoxin system in Escherichia coli O157:H7 is composed of 29 amino acids and its endogenous expression inhibits E. coli growth. However, little is known about its inhibitory mechanism. In this study, we demonstrate that the ZorO localized in the inner membrane affects the plasma membrane integrity and potential when expressed in E. coli cells, which triggers the production of cytotoxic hydroxyl radicals. We further show that five internal amino acids (Ala-Leu-Leu-Arg-Leu; ALLRL) of ZorO are necessary for its toxicity. This result prompted us to address the potential of the synthetic ALLRL peptide as an antimicrobial. Exogenously-added ALLRL peptide to Gram-positive bacteria, Staphylococcus aureus and Bacillus subtilis, and a fungus, Candida albicans, trigger cell membrane damage and exhibit growth defect, while having no effect on Gram-negative bacterium, E. coli. The ALLRL peptide retains its activity under the physiological salt concentrations, which is in contrast to natural antimicrobial peptides. Importantly, this peptide has no toxicity against mammalian cells. Taken together, an effective and short peptide, ALLRL, would be an attractive antimicrobial to Gram-positive bacteria and C. albicans.

Rivaroxaban-related acute kidney injury in a patient with IgA vasculitis.

Anticoagulants have recently been recognised as a cause of acute kidney injury (AKI). We describe the case of a 75-year-old man with IgA vasculitis and atrial fibrillation treated with rivaroxaban, who presented with macroscopic haematuria and an acute decline in renal function. Two months before referral, he noted palpable purpuric lesions and was diagnosed with IgA vasculitis based on skin biopsy findings; the skin lesion disappeared following treatment with a steroid external preparation. Renal biopsy revealed glomerular haemorrhage and red blood cell casts. Although rivaroxaban was withdrawn, his kidney function worsened and he was started on haemodialysis. His renal function did not recover. To the best of our knowledge, this is the first case of direct oral anticoagulant (DOAC)-related AKI in systemic vasculitis. During DOAC therapy, close monitoring of a patient's urinalysis results and their renal function may be required for patients with systemic vasculitis to avoid AKI.

Optimization of ionic liquid-incorporated PLGA nanoparticles for treatment of biofilm infections.

Ionic liquids (ILs) containing imidazolium cations have a number of useful properties, such as high permeability to cells, high antimicrobial activity, and good biocompatibility. With the aid of ILs, transdermal delivery, solubilization of poorly soluble drugs were developed and therapeutic effects were improved. In this work, 1­butyl­3­methylimidazolium hexafluorophosphate-incorporated, chitosan-modified, submicron-sized poly(dl­lactide­co­glycolide) (PLGA) nanoparticles (NPs) were prepared using the emulsion solvent diffusion method for the treatment of biofilm infections. Prepared IL-incorporated PLGA NPs using surfactants such as Tween-80 and poloxamer-188 showed a high antibacterial activity to the bacterial cells under the biofilm. Additionally, antibacterial mechanism of IL-incorporated PLGA NPs was revealed by annular dark field scanning transmission electron microscopy combined a simple sample pretreatment method. We established a drug delivery system using IL-incorporated PLGA NPs to enhance the potential of polymeric nanocarriers for treating biofilm infections.

SEM imaging of the stimulatory response of RAW264.7 cells against Porphyromonas gingivalis using a simple technique employing new conductive materials.

In the medical biology, it is essential to understand not only biological morphology but also the interaction between biological materials and agents. To study these, electron microscopy (EM) is often utilized. However, sample preparation techniques for EM require a high level of skill and a considerable time. Here, we conducted EM using a simple technique employing a conductive liquid, BEL-1, and compared the results with another simple technique employing an ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4 ]). BEL-1 was used for sample pretreatment, and the morphologies of the mouse RAW 264.7 cell line, Porphyromonas gingivalis, and the RAW 264.7 cell line were stimulated via co-incubation with P. gingivalis and observed using field emission scanning EM (FE-SEM). In the present study, the inflammation-induced system of P. gingivalis was successfully established. FE-SEM results revealed the fine morphology of the RAW 264.7 cell line and P. gingivalis and confirmed a morphological change in the RAW 264.7 cell line caused by P. gingivalis stimulation. Using the developed sample preparation technique employing BEL-1, high-contrast and high-resolution observations of deformable biological materials were conducted without any difficulty or the necessity for complicated technique. This morphological information and the developed techniques can contribute to reveal the interaction between biological materials and agents and thereby accelerate drug formulation and disease treatment. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1280-1285, 2018.