Origin of iodine preferential attack at sulfur in phosphorothioate and subsequent P-O or P-S bond dissociation.

Iodine-induced cleavage at phosphorothioate DNA (PT-DNA) is characterized by extremely high sensitivity (∼1 phosphorothioate link per 106 nucleotides), which has been used for detecting and sequencing PT-DNA in bacteria. Despite its foreseeable potential for wide applications, the cleavage mechanism at the PT-modified site has not been well established, and it remains unknown as to whether or not cleavage of the bridging P-O occurs at every PT-modified site. In this work, we conducted accurate ωB97X-D calculations and high-performance liquid chromatography-mass spectrometry to investigate the process of PT-DNA cleavage at the atomic and molecular levels. We have found that iodine chemoselectively binds to the sulfur atom of the phosphorothioate link via a strong halogen-chalcogen interaction (a type of halogen bond, with binding affinity as high as 14.9 kcal/mol) and thus triggers P-O bond cleavage via phosphotriester-like hydrolysis. Additionally, aside from cleavage of the bridging P-O bond, the downstream hydrolyses lead to unwanted P-S/P-O conversions and a loss of the phosphorothioate handle. The mechanism we outline helps to explain specific selectivity at the PT-modified site but also predicts the dynamic stoichiometry of P-S and P-O bond breaking. For instance, Tris is involved in the cascade derivation of S-iodo-phosphorothioate to S-amino-phosphorothioate, suppressing the S-iodo-phosphorothioate hydrolysis to a phosphate diester. However, hydrolysis of one-third of the Tris-O-grafting phosphotriester results in unwanted P-S/P-O conversions. Our study suggests that bacterial DNA phosphorothioation may more frequently occur than previous bioinformatic estimations have predicted from iodine-induced deep sequencing data.

Optimization of Calcium Fluoride Crystallization Process for Treatment of High-Concentration Fluoride-Containing Semiconductor Industry Wastewater.

This study utilized a fluidized bed reactor (FBR) for fluoride removal from high-concentration fluoride-ion-containing simulated semiconductor industry wastewater and recovered high-purity CaF2 crystals. The effects of hydraulic retention time (HRT), pH, Ca2+ to F- ratio, upflow velocity, seed size and seed bed height were investigated by performing lab-scale batch experiments. Considering fluoride removal and CaF2 crystallization efficiency, 5 h HRT, pH 6, seed height of 50 cm and [Ca2+]/[F-] ratio of 0.55 (mol/mol) were found to be optimum. The effect of the interaction between the important process parameters on fluoride removal was further analyzed using response surface methodology (RSM) experimental design. The results showed that all the individual parameters have a significant impact (p = 0.0001) on fluoride removal. SEM-EDX and FTIR analysis showed the composition of the crystals formed inside FBR. HR-XRD analysis confirmed that the crystalline structure of samples was mainly CaF2. The results clearly demonstrated the feasibility of silica seed material containing FBR for efficient removal and recovery of fluoride as high-purity calcium fluoride crystals.

Process Intensification for Enhanced Fluoride Removal and Recovery as Calcium Fluoride Using a Fluidized Bed Reactor.

This study explored the feasibility of fluoride removal from simulated semiconductor industry wastewater and its recovery as calcium fluoride using fluidized bed crystallization. The continuous reactor showed the best performance (>90% fluoride removal and >95% crystallization efficiency) at a calcium-to-fluoride ratio of 0.6 within the first 40 days of continuous operation. The resulting particle size increased by more than double during this time, along with a 36% increase in the seed bed height, indicating the deposition of CaF2 onto the silica seed. The SEM-EDX analysis showed the size and shape of the crystals formed, along with the presence of a high amount of Ca-F ions. The purity of the CaF2 crystals was determined to be 91.1% though ICP-OES analysis. Following the continuous experiment, different process improvement strategies were explored. The addition of an excess amount of calcium resulted in the removal of an additional 6% of the fluoride; however, compared to this single-stage process, a two-stage approach was found to be a better strategy to achieve a low effluent concentration of fluoride. The fluoride removal reached 94% with this two-stage approach under the optimum conditions of 4 + 1 h HRT combinations and a [Ca2+]/[F-] ratio of 0.55 and 0.7 for the two reactors, respectively. CFD simulation showed the impact of the inlet diameter, bottom-angle shape, and width-to-height ratio of the reactor on the mixing inside the reactor and the possibility of further improvement in the reactor performance by optimizing the FBR configuration.

Pigmented contact dermatitis and hair dyes: A retrospective case-control multicentre study in Korea.

BACKGROUND: Pigmented contact dermatitis (PCD), a rare variant of non-eczematous contact dermatitis, is clinically characterized by sudden-onset brown or grey pigmentation on the face and neck. It is hypothesized to be caused by repeated contact with low levels of allergens. OBJECTIVES: This study evaluated the risk of using hair dyes in patients with PCD in Korea. METHODS: A total of 1033 PCD patients and 1366 controls from 31 university hospitals were retrospectively recruited. We collected and analysed the data from the patient group, diagnosed through typical clinical findings of PCD and the control group, which comprised age/sex-matched patients who visited the participating hospitals with pre-existing skin diseases other than current allergic disease or PCD. RESULTS: Melasma and photosensitivity were significantly more common in the control group, and a history of contact dermatitis was more common in the PCD group. There were significantly more Fitzpatrick skin type V participants in the PCD group than in the control group. There was no significant difference in sunscreen use between the groups. Using dermatologic medical history, Fitzpatrick skin type and sunscreen use as covariates, we showed that hair dye use carried a higher PCD risk (odds ratio [OR] before adjustment: 2.06, confidence interval [CI]: 1.60-2.65; OR after adjustment: 2.74, CI: 1.88-4.00). Moreover, henna users had a higher risk of PCD (OR before adjustment: 5.51, CI: 4.07-7.47; OR after adjustment: 7.02, CI: 4.59-10.74), indicating a significant increase in the risk of PCD with henna dye use. Contact dermatitis history was more prevalent in henna users than in those using other hair dyes in the PCD group (17.23% vs. 11.55%). CONCLUSION: Hair dye use is a risk factor for PCD. The risk significantly increased when henna hair dye was used by those with a history of contact dermatitis.

Pacinian corpuscle hyperplasia in a 6-year-old girl.

We present a rare case of Pacinian corpuscle hyperplasia (PCH) presenting with typical finger pain in a 6-year-old girl. As appendages in children are smaller than those in adults, diagnostic criteria are needed for pathological confirmation of PCH in pediatric patients.

Effectiveness of nurse-led interventions on medication adherence in adults taking medication for metabolic syndrome: A systematic review and meta-analysis.

AIMS AND OBJECTIVES: To determine the effectiveness of nurse-led interventions on medication adherence, medication knowledge and clinical outcomes in adults taking medication for metabolic syndrome. BACKGROUND: Despite the significance of interventions designed to improve medication adherence, a systematic review of nurse-led intervention studies for metabolic syndrome is lacking. DESIGN: A systematic review and meta-analysis of randomised controlled trials. METHODS: The study was conducted following the PRISMA guidelines checklist. PubMed, EMBASE, PsychINFO, CINAHL, Cochrane CENTRAL and other manual sources were searched in May 2021.The quality assessment was conducted using the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. Comprehensive Meta-Analysis 3.0 was used to calculate the pooled effect sizes with 95% confidence intervals. RESULTS: This review included 20 studies of nurse-led medication adherence interventions in 6017 adults at risk for metabolic syndrome. The pooled effect size using the random effects model indicated that nurse-led interventions had a significantly moderate impact on enhancing medication adherence and medication knowledge and improving selected clinical outcomes of available studies in nurse-led intervention groups compared with control groups. Duration of intervention (median 12 weeks), mode of delivery (group vs. individual) and using multiple strategies influenced outcomes of nurse-led medication adherence interventions. The results revealed that interventions of moderate- to high-quality studies were more likely to show significant improvements in medication adherence than those of low-quality studies. CONCLUSION: The meta-analyses showed that nurse-led interventions may enhance medication adherence and knowledge and improve clinical outcomes of this population. RELEVANCE TO CLINICAL PRACTICE: The findings may contribute to evidence-based information about nurse-led intervention and its selection of appropriate interventions for improving medication adherence in this population. PATIENT OR PUBLIC CONTRIBUTION: Patients or the public were not directly involved in this review.

Comparisons of Physicochemical Properties, Bacterial Diversities, Isoflavone Profiles and Antioxidant Activities on Household and Commercial doenjang.

In this study, the physicochemical properties (pH, acidity, salinity, and soluble protein), bacterial diversities, isoflavone contents, and antioxidant activities of doenjang (fermented soy paste), household doenjang (HDJ), and commercial doenjang (CDJ), were assessed and compared. The values of pH 5.14-5.94 and acidity 1.36-3.03%, indicated a similar level in all doenjang. The salinity was high in CDJ at 12.8-14.6%, and the protein contents (25.69-37.54 mg/g) were generally high in HDJ. Forty-three species were identified from the HDJ and CDJ. The main species were verified to be Bacillus amyloliquefaciens (B. amyloliquefaciens), B. amyloliquefaciens subsp. plantarum, Bacillus licheniformis, Bacillus sp. and Bacillus subtilis. Comparing the ratios of isoflavone types, the HDJ has an aglycone ratio of >80%, and 3HDJ indicates a ratio of isoflavone to aglycone of 100%. In the CDJ, except 4CDJ, glycosides account for a high proportion of more than 50%. The results of antioxidant activities and DNA protection effects were variedly confirmed regardless of HDJs and CDJs. Through these results, it is judged that HDJs have a variety of bacterial species compared to CDJs, and these are biologically active and converted from glycoside to aglycone. Bacterial distribution and isoflavone contents could be used as basic data.

The effects of 1,25(OH)2 D3 treatment on immune responses and intracellular metabolic pathways of bone marrow-derived dendritic cells from lean and obese mice.

Vitamin D affects differentiation, maturation, and activation of dendritic cells (DCs). Obesity-related immune dysfunction is associated with metabolic changes in immune cells. Objectives of the study are to investigate the effects of vitamin D and obesity on immune responses and markers related to immunometabolism of bone marrow-derived dendritic cells (BMDCs). Bone marrow cells (BMCs) were isolated from lean and obese mice, and BMDCs were generated by culturing BMCs with rmGM-CSF. BMDCs were treated with 1 or 10 nM of 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ), and maturation was induced by LPS (50 ng/ml) stimulation for 24 hr. Cell phenotypes, cytokine productions, and expression of proteins and genes involved in Akt/mTOR signaling pathway and glycolytic pathway were determined. 1,25(OH)2 D3 treatment inhibited differentiation of BMDCs (CD11c+ %), expression of phenotypes related with DC function (MHC class II and CD86) and production of IL-12p70 in both lean and obese mice. The expression of PD-L1 and the ratio of IL-10/IL-12p70 were increased by 1,25(OH)2 D3 . With 1,25(OH)2 D3 treatment, Akt/mTOR signaling pathway was suppressed, and expression of genes related to glycolysis (Glut1, Pfkfb4, and Hif1A) was increased. The upregulation of glycolysis-related genes observed with 1,25(OH)2 D3 treatment seems to be associated with the induction of tolerogenic features of BMDCs from lean and obese mice, and Hif1A seems to have a potential role in conveying the effect of 1,25(OH)2 D3 on glycolysis.

Reversible switching of leukemic cells to a drug-resistant, stem-like subset via IL-4-mediated cross-talk with mesenchymal stroma.

Chemoresistance of leukemic cells has largely been attributed to clonal evolution secondary to accumulating mutations. Here, we show that a subset of leukemic blasts in contact with the mesenchymal stroma undergo cellular conversion into a distinct cell type that exhibits a stem cell-like phenotype and chemoresistance. These stroma-induced changes occur in a reversible and stochastic manner driven by cross-talk, whereby stromal contact induces interleukin-4 in leukemic cells that in turn targets the mesenchymal stroma to facilitate the development of new subset. This mechanism was dependent on interleukin-4-mediated upregulation of vascular cell adhesion molecule- 1 in mesenchymal stroma, causing tight adherence of leukemic cells to mesenchymal progenitors for generation of new subsets. Together, our study reveals another class of chemoresistance in leukemic blasts via functional evolution through stromal cross-talk, and demonstrates dynamic switching of leukemic cell fates that could cause a non-homologous response to chemotherapy in concert with the patient-specific microenvironment.

Male breast cancer presenting in accessory axillary breast.

We present a rare case of male axillary accessory breast cancer, which is extremely rare and is indistinguishable from lymphadenopathy and other malignancies, such as lymphoma and skin-derived tumors. Clinicians should consider accessory breast cancer in the differential diagnosis even in men, particularly in those who present with superficially located tumors with adjacent accessory breast tissue.

Anthracene-Triphenylamine-Based Platinum(II) Metallacages as Synthetic Light-Harvesting Assembly.

Two trigonal prismatic metallacages 1 and 2 bearing triphenylamine and anthracene moieties are designed and synthesized to fabricate artificial light-harvesting systems (LHSs). These two cages are prepared via the coordination-driven self-assembly of two anthracene-triphenylamine-based tripyridyl ligand 3, three dicarboxylates, and six 90° Pt(II) acceptors. The design of the anthracene-triphenylamine chromophore makes possible the tunable excited-state property (like the emissive transition energy and lifetime) as a function of the solvent polarity, temperature, and concentration. The synergistic photophysical footprint of these metallacages, defined by their high absorptivity and emission quantum yield (QY) relative to the free ligand 3, signifies them as a superior light sensitizer component in an LHS. In the presence of the fluorescent dye Nile Red (NR) as an energy acceptor, the metallacages display efficient (>93%) excited energy transfer to NR through an apparent static quenching mechanism in viscous dimethyl sulfoxide solvent.

Nonenzymatic Stereoselective S-Glycosylation of Polypeptides and Proteins.

Here we report a nonenzymatic glycosylation reaction that builds axial S-glycosidic bonds under biorelevant conditions. This strategy is enabled by the design and use of allyl glycosyl sulfones as precursors to glycosyl radicals and exploits the exceptional functional group tolerance of radical processes. Our method introduces a variety of unprotected glycosyl units to the cysteine residues of peptides in a highly selective fashion. Through developing the second-generation protocol, we applied our method in the direct glycosylation of complex polypeptides and proteins. Computational studies were performed to elucidate the reaction mechanism.

Arene-Perfluoroarene Interactions in Solution.

A systematic study of arene-perfluoroarene interactions in solution is presented. Using a combination of NMR titration experiments, X-ray crystallography, and computational analysis, we analyze the effects of fluorination, substituents, ring size, and solvation on the arene-perfluoroarene interaction. We find that fluorination, extension of the π systems, and enhancement of solvent polarity greatly stabilize the stacking energy up to 3 orders of magnitude (Ka = <1 to 6000 M-1), with the highest Ka achieved for the interaction of water-soluble variants of perfluoronaphthalene and anthracene in buffered D2O (pD = 12). Combining computational and experimental results, we conclude that this impressive binding energy is a result of enthalpically favorable electrostatic and dispersion interactions as well as the entropically driven hydrophobic effect. The enhanced understanding of arene-perfluoroarene interactions in aqueous solution sets the stage for the implementation of this abiotic intermolecular interaction in biology and medicine.

Effect of Tranexamic Acid Administration on Postoperative Ecchymosis and Edema in Excision of Lipomas.

BACKGROUND: Previous studies have shown that systemic tranexamic acid reduces bleeding during soft tissue surgeries and reduces postoperative ecchymosis and edema experienced by surgical patients. OBJECTIVE: To evaluate the effect of postoperative tranexamic acid administration on the reduction of ecchymosis and edema after lipoma surgery. MATERIALS AND METHODS: A total of 40 patients who underwent lipoma excision were included in the comparative analysis. In the tranexamic acid group (n = 20), 1 g of tranexamic acid was administered daily for 5 consecutive postoperative days. Tranexamic acid was not administered to the control group (n = 20). The severity of ecchymosis and edema at the first visit after surgery was rated on a 4-point scale by 2 blinded dermatologists. RESULTS: The mean interval of the initial visit after surgery was 1.1 ± 0.5 (range: 1-4) days. Mean ecchymosis scores were significantly lower in the tranexamic acid group (0.5 ± 0.8) than in the control group (1.2 ± 1.0) (p < .05). No statistical difference was seen in mean edema scores between groups (0.5 ± 0.6 in tranexamic acid vs 0.7 ± 0.8 in control). CONCLUSION: We observed that postoperative administration of tranexamic acid significantly decreased ecchymosis in lipoma excision.

The Beneficial Effect on Pigmentation Using Laser Epilation as an Initial Treatment Approach for Becker's Nevus in Asian Skin.

Becker's nevus (BN) clinically presents as brown patches with hypertrichosis. The risk of pigmentary changes still remains a concern when using lasers to treat Asian patients with BN. We aimed to evaluate the outcomes on reduction of hairs and pigment of BN using the long-pulsed 1064-nm Nd:YAG (LPNY) and/or 755-nm alexandrite (LP-Alex), before treating pigment in earnest. A total of 13 subjects were treated with the LPNY (n = 8), the LP-Alex (n = 4), and both (n = 1). Improvements on hair removal and pigment reduction were assessed using a 5-point global assessment scale. Patient satisfaction was also assessed. Treatment parameters were within those commonly used for the purpose of epilation. The average follow-up period was 19.5 ± 12.3 weeks, and the mean total number of sessions was 2.0. Eleven subjects reported >50% improvement in hair removal (11/13, 86.7%), and pigment reduction of >50% improvement was observed in 9 subjects (9/13, 69.2%). Patient satisfaction showed >50% lesion clearance in 84.6%. Hair removal settings of LPNY and LP-Alex were effective in both hypertrichosis and pigment reduction in the initial strategy of treatment of BN in skin of color.

More Than π-π-π Stacking: Contribution of Amide-π and CH-π Interactions to Crotonyllysine Binding by the AF9 YEATS Domain.

Lysine crotonylation (Kcr) is a histone post-translational modification that is implicated in numerous epigenetic pathways and diseases. Recognition of Kcr by YEATS domains has been proposed to occur through intermolecular amide-π and alkene-π interactions, but little is known about the driving force of these key interactions. Herein, we probed the recognition of lysine crotonylation and acetylation by the AF9 YEATS domain through incorporation of noncanonical Phe analogs with distinct electrostatics at two positions. We found that amide-π interactions between AF9 and acyllysines are electrostatically tunable, with electron-rich rings providing more favorable interactions. This differs from trends in amide-heteroarene interactions and provides insightful information for therapeutic design. Additionally, we report for the first time that CH-π interactions at Phe28 directly contribute to AF9's recognition of acyllysines, illuminating differences among YEATS domains, as this residue is not highly conserved but has been shown to impart selectivity for specific post-translational modification.

Me-too validation study for in vitro skin irritation test with a reconstructed human epidermis model, KeraSkin™ for OECD test guideline 439.

We conducted a me-too validation study to confirm the reproducibility, reliability, and predictive capacity of KeraSkin™ skin irritation test (SIT) as a me-too method of OECD TG 439. With 20 reference chemicals, within-laboratory reproducibility (WLR) of KeraSkin™ SIT in the decision of irritant or non-irritant was 100%, 100%, and 95% while between-laboratory reproducibility (BLR) was 100%, which met the criteria of performance standard (PS, WLR≥90%, BLR≥80%). WLR and BLR were further confirmed with intra-class correlation (ICC, coefficients >0.950). WLR and BLR in raw data (viability) were also shown with a scatter plot and Bland-Altman plot. Comparison with existing VRMs with Bland-Altman plot, ICC and kappa statistics confirmed the compatibility of KeraSkin™ SIT with OECD TG 439. The predictive capacity of KeraSkin™ SIT was estimated with 20 reference chemicals (the sensitivity of 98.9%, the specificity of 70%, and the accuracy of 84.4%) and additional 46 chemicals (for 66 chemicals [20 + 46 chemicals, the sensitivity, specificity and accuracy: 95.2%, 82.2% and 86.4%]). The receiver operating characteristic (ROC) analysis suggested a potential improvement of the predictive capacity, especially sensitivity, when changing cut-off (50% → 60-75%). Collectively, the me-too validation study demonstrated that KeraSkin™ SIT can be a new me-too method for OECD TG 439.

Bacterial Tetrabromopyrrole Debrominase Shares a Reductive Dehalogenation Strategy with Human Thyroid Deiodinase.

Enzymatic dehalogenation is an important and well-studied biological process in both the detoxification and catabolism of small molecules, many of which are anthropogenic in origin. However, dedicated dehalogenation reactions that replace a halogen atom with a hydrogen are rare in the biosynthesis of natural products. In fact, the debrominase Bmp8 is the only known example. It catalyzes the reductive debromination of the coral settlement cue and the potential human toxin 2,3,4,5-tetrabromopyrrole as part of the biosynthesis of the antibiotic pentabromopseudilin. Using a combination of protein crystallography, mutagenesis, and computational modeling, we propose a catalytic mechanism for Bmp8 that is reminiscent of that catalyzed by human deiodinases in the maintenance of thyroid hormones. The identification of the key catalytic residues enabled us to recognize divergent functional homologues of Bmp8. Characterization of one of these homologues demonstrated its debromination activity even though it is found in a completely distinct genomic context. This observation suggests that additional enzymes outside those associated with the tetrabromopyrrole biosynthetic pathway may be able to alter the lifetime of this compound in the environment.

Clinical Outcome of 1064-nm Picosecond Neodymium-Doped Yttrium Aluminium Garnet Laser for the Treatment of Hypertrophic Scars.

BACKGROUND: Currently no study has evaluated the effect of the novel 1064-nm picosecond neodymium-doped:yttrium aluminium garnet laser (ps-Nd:YAG) for reducing Hypertrophic scarring (HS). OBJECTIVE: The aim of this study was to verify the efficacy and safety of a 1064-nm ps-Nd:YAG in the management of HS. MATERIALS AND METHODS: A retrospective chart review and photographic analysis were conducted on patients treated with a low-fluence 1064-nm ps-Nd:YAG for HS improvement. The Vancouver Scar Scale (VSS), 5-point Global Assessment Score (GAS), and patient satisfaction score were used to determine the effect of scar improvement. RESULTS: A total of 24 Korean patients (9 males and 15 females; mean age of 33.25 ± 15.50 years) were retrospectively evaluated. Mean treatment settings were 1064-nm wavelength, 750 ps pulse duration, 7.94 mm spot size, 0.93 J/cm2 fluence, and 9.69 Hz frequency. The average VSS score decreased significantly (from 5.33 to 2.71) after laser treatment (p < 0.001). The average GAS (3.02 ± 0.93) showed fair cosmetic improvement, and patient satisfaction scores (6.88 ± 2.66) indicated moderate satisfaction. CONCLUSION: The novel low-fluence 1064-nm ps-Nd:YAG could be considered as an effective and safe optional modality for the treatment of HS in Asian skin.

Skin subtype categorization based on a new questionnaire for Korean women.

BACKGROUND: Several terms have been used to characterize skin types. However, these are not based on evident dermatologic definitions, which usually include subjective and psychological properties. OBJECTIVE: The objective of this study is to establish a new practical questionnaire to classify skin subtypes in Korean women to establish treatment and skin care guidance. METHODS: Eight experts developed consensus statements about skin types and created a questionnaire. The content was categorized into four major subtypes: dry or non-dry; oily or nonoily; sensitive or nonsensitive; and pigmented or nonpigmented. A total of 512 patients completed the questionnaire. Correlations with age, skin Fitzpatrick's phototypes, and dermatologic comorbidities were analyzed. RESULTS: Korean women commonly have oily skin but complain of dryness after cleansing. They are especially sensitive to skin care products and prone to developing pigmentary lesions. There was a trend in the proportion of dry skin subtype that increased as pigmented skin increased and oily skin decreased with advanced age. The proportion of sensitive skin was higher in patients with dermatologic comorbidities. The proportion of the pigmented skin was higher in darker Fitzpatrick skin phototypes. CONCLUSION: This is the first questionnaire established for Korean women to classify practical skin subtypes and may provide a basis for treating various skin conditions.