Correction of Congenital Syndactyly of the Hand with Minimal Full-Thickness Skin Graft from the Weight-Bearing Midline Plantar Area.

BACKGROUND: Traditional skin grafts for syndactyly often cause color mismatches and unsightly donor sites, whereas no-skin-graft methods leave noticeable dorsal hand scars. This study presents plantar full-thickness skin graft (FTSG) from the weight-bearing midline area for syndactyly repair, a novel approach not previously reported in the literature. METHODS: The study included three groups of patients with congenital syndactyly of the hand who underwent primary operations with plantar FTSG (n=70), groin FTSG (n=20), and no-skin-graft techniques (n=22). Postoperative outcomes were evaluated by an assessment panel, and guardians' satisfaction scores were measured. Color similarity between the graft and surrounding skin was assessed using a three-dimensional color space. RESULTS: The plantar FTSG group demonstrated a significantly higher likelihood of receiving an 'excellent' rating compared to the groin FTSG group, with an odds ratio of 6.30 (p<0.001). Color difference analysis showed that plantar FTSG more closely matched surrounding skin color than groin FTSG (6.33 vs. 22.57, p<0.001). Guardians reported greater satisfaction with outcomes on the hand in the plantar FTSG group compared to the groin FTSG and no-skin-graft groups (7.16 vs. 5.05 and 4.36, p<0.001). Satisfaction with donor sites was also significantly higher in the plantar FTSG group than in the groin FTSG group (8.23 vs. 6.30, p<0.001). CONCLUSION: Correction of congenital hand syndactyly using midline plantar FTSG from the weight-bearing area can reduce scarring on the hand dorsum, ensure superior color similarity with surrounding skin, and offer inconspicuous donor sites compared to no-skin-graft or groin FTSG techniques.

Augmentation of NK-cell activity and immunity by combined natural polyphenols and saccharides in vitro and in vivo.

Curcuma longa and Sargassum coreanum are commonly used in traditional pharmaceutical medicine to improve immune function in chronic diseases. The present study was designed to systematically elucidate the in vitro and in vivo immuno-enhancing effects of a combination of C. longa and S. coreanum extracts (CS) that contain polyphenols and saccharides as functional molecules in a cyclophosphamide (Cy)-induced model of immunosuppression. In primary splenocytes, we observed the ameliorative effects of CS on a Cy-induced immunosuppression model with low cytotoxicity and an optimal mixture procedure. CS treatment enhanced T- and B-cell proliferation, increased splenic natural killer-cell activity, and restored cytokine release. Wistar rats were orally administered low (30 mg/kg), intermediate (100 mg/kg), or high (300 mg/kg) doses of CS for four weeks, followed by oral administration of Cy (5 mg/kg) for four weeks. Compared with the vehicle group, low-, intermediate-, and high-dose CS treatment accelerated dose-dependent recovery of the serum level of tumor necrosis factor-α, interferon-γ, interleukin-2, and interleukin-12. These results suggest that CS treatment accelerates the amelioration of immune deficiency in Cy-treated primary splenocytes and rats, which supports considering it for immunity maintenance. Our findings provide experimental evidence for further research and clinical application in immunosuppressed patients.

Simultaneous or Delayed Free Tissue Transfer in Combination with Replantation Surgery.

In hand and upper extremity replantation surgery, simultaneous free flap reconstruction restores the physiologic circulation to the amputated part, ensuring its survival, and promotes wound healing through anatomic restoration. Especially in digit replantation, an arterialized venous flap serves to reconstruct both vessel and soft tissue defects simultaneously. Delayed free flap reconstruction aims to enhance both functional improvement and cosmetic acceptance in a successfully replanted part using flaps that include functioning muscle, bone, joint, nerve, and soft tissue.

The Expanded Application of the Acellular Dermal Matrix: Traumatic Nail Bed Defect of the Digits.

Reconstruction of traumatic nail bed defects in the digits is a frequently encountered procedure, yet often presents many challenges. In such scenarios, staged procedures may be required with significant limitations in shape and increased donor site morbidity, particularly when multiple defects are present. In this study, we introduce a simple method for the reconstruction of nail bed defects using an acellular dermal matrix (ADM). The study involved 19 digits with nail defects, which underwent reconstruction using an ADM graft. The surgical procedure was performed on all patients on the day of injury, after which they were promptly discharged. The dimensions of the defect ranged from 0.5 × 0.5 cm to a maximum of 2 × 3 cm (average, 0.9 × 1.4 cm). Final examinations were performed at postoperative 5-11 months (average, 6.6 months). All ADM grafts were successfully taken. Nail growth was observed at an average of 4 months after surgery in the treated finger. The surgical results were retrospectively evaluated using the Zook criteria. Outcomes were "excellent" in 11 patients (57.9%), "very good" in five patients (26.3%), "good" in two patients (10.5%), and "fair" in one patient (5.2%). The expanded application of ADM explored in this study illustrates a straightforward method for the reconstruction of traumatic nail bed defects, providing effective results in a single stage without incurring donor site morbidity.

Enhancing the thermostability and activity of glycosyltransferase UGT76G1 via computational design.

The diterpene glycosyltransferase UGT76G1, derived from Stevia rebaudiana, plays a pivotal role in the biosynthesis of rebaudioside A, a natural sugar substitute. Nevertheless, its potential for industrial application is limited by certain enzymatic characteristics, notably thermostability. To enhance the thermostability and enzymatic activity, we employed a computational design strategy, merging stabilizing mutation scanning with a Rosetta-based protein design protocol. Compared to UGT76G1, the designed variant 76_4 exhibited a 9 °C increase in apparent Tm, a 2.55-fold increase rebaudioside A production capacity, and a substantial 11% reduction in the undesirable byproduct rebaudioside I. Variant 76_7 also showed a 1.91-fold enhancement rebaudioside A production capacity, which was maintained up to 55 °C, while the wild-type lost most of its activity. These results underscore the efficacy of structure-based design in introducing multiple mutations simultaneously, which significantly improves the enzymatic properties of UGT76G1. This strategy provides a method for the development of efficient, thermostable enzymes for industrial applications.

ANCA: artificial nucleic acid circuit with argonaute protein for one-step isothermal detection of antibiotic-resistant bacteria.

Endonucleases have recently widely used in molecular diagnostics. Here, we report a strategy to exploit the properties of Argonaute (Ago) proteins for molecular diagnostics by introducing an artificial nucleic acid circuit with Ago protein (ANCA) method. The ANCA is designed to perform a continuous autocatalytic reaction through cross-catalytic cleavage of the Ago protein, enabling one-step, amplification-free, and isothermal DNA detection. Using the ANCA method, carbapenemase-producing Klebsiella pneumoniae (CPKP) are successfully detected without DNA extraction and amplification steps. In addition, we demonstrate the detection of carbapenem-resistant bacteria in human urine and blood samples using the method. We also demonstrate the direct identification of CPKP swabbed from surfaces using the ANCA method in conjunction with a three-dimensional nanopillar structure. Finally, the ANCA method is applied to detect CPKP in rectal swab specimens from infected patients, achieving sensitivity and specificity of 100% and 100%, respectively. The developed method can contribute to simple, rapid and accurate diagnosis of CPKP, which can help prevent nosocomial infections.

Fisetin Inhibits UVA-Induced Expression of MMP-1 and MMP-3 through the NOX/ROS/MAPK Pathway in Human Dermal Fibroblasts and Human Epidermal Keratinocytes.

Fisetin is a flavonoid found in plants and has been reported to be effective in various human diseases. However, the effective mechanisms of ultraviolet-A (UVA)-mediated skin damage are not yet clear. In this study, we investigated the protective mechanisms of fisetin regarding UVA-induced human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs) damages. Fisetin showed a cytoprotective effect against UVA irradiation and suppressed matrix metalloproteinases (MMPs), MMP-1, and MMP-3 expression. In addition, fisetin was rescued, which decreased mRNA levels of pro-inflammatory cytokines, reactive oxygen species production, and the downregulation of MAPK/AP-1 related protein and NADPH oxidase (NOX) mRNA levels. Furthermore, UVA-induced MMP-1 and MMP-3 were effectively inhibited by siRNAs to NOX 1 to 5 in HDFs and HEKs. These results indicate that fisetin suppresses UVA-induced damage through the NOX/ROS/MAPK pathway in HDFs and HEKs.

Hierarchically Porous Carbon Networks Derived from Chitosan for High-Performance Electrochemical Double-Layer Capacitors.

Activated carbon (AC) compounds derived from biomass precursors have garnered significant attention as electrode materials in electric double-layer capacitors (EDLCs) due to their ready availability, cost-effectiveness, and potential for mass production. However, the accessibility of their active sites in electrochemistry has not been investigated in detail. In this study, we synthesized two novel macro/micro-porous carbon structures prepared from a chitosan precursor using an acid/potassium hydroxide activation process and then examined the relationship between their textural characteristics and capacitance as EDLCs. The material characterizations showed that the ACs, prepared through different activation processes, differed in porosity, with distinctive variations in particle shape. The sample activated at 800 °C (Act-chitosan) was characterized by plate-shaped particles, a specific surface area of 4128 m2/g, and a pore volume of 1.87 cm3/g. Assessment of the electrochemical characteristics of Act-chitosan showed its remarkable capacitance of 183.5 F/g at a scan rate of 5 mV/s, and it maintained exceptional cyclic stability even after 10,000 cycles. The improved electrochemical performance of both chitosan-derived carbon structures could thus be attributed to their large, well-developed active sites within pores < 2 nm, despite the fact that interconnected macro-porous particles can enhance ion accessibility on electrodes. Our findings provide a basis for the fabrication of biomass-based materials with promising applications in electrochemical energy storage systems.

Effect of Fluorination Position on the Crystalline Structure and Stretchability of Intrinsically Stretchable Polymer Semiconductors.

A clear understanding of the structure-property relationship of intrinsically stretchable polymer semiconductors (ISPSs) is essential for developing high-performance polymer-based electronics. Herein, we investigate the effect of the fluorination position on the crystalline structure, charge-carrier mobility, and stretchability of polymer semiconductors based on a benzodithiophene-co-benzotriazole configuration. Although four different polymer semiconductors showed similar field-effect mobilities for holes (µ ≈ 0.1 cm2 V-1 s-1), polymer semiconductors with nonfluorinated backbones exhibited improved thin-film stretchability confirmed with crack onset strain (εc ≈ 20%-50%) over those of fluorinated counterparts (εc ≤ 10%). The enhanced stretchability of polymer semiconductors with a nonfluorinated backbone is presumably due to the higher face-on crystallite ratio and π-π stacking distance in the out-of-plane direction than those of the other polymer semiconductors. These results provide new insights into how the thin-film stretchability of polymer semiconductors can be improved by using precise molecular tailoring without deteriorating electrical properties.

Design of hypoxia responsive CRISPR-Cas9 for target gene regulation.

The CRISPR-Cas9 system is a widely used gene-editing tool, offering unprecedented opportunities for treating various diseases. Controlling Cas9/dCas9 activity at specific location and time to avoid undesirable effects is very important. Here, we report a conditionally active CRISPR-Cas9 system that regulates target gene expression upon sensing cellular environmental change. We conjugated the oxygen-sensing transcription activation domain (TAD) of hypoxia-inducing factor (HIF-1α) with the Cas9/dCas9 protein. The Cas9-TAD conjugate significantly increased endogenous target gene cleavage under hypoxic conditions compared with that under normoxic conditions, whereas the dCas9-TAD conjugate upregulated endogenous gene transcription. Furthermore, the conjugate system effectively downregulated the expression of SNAIL, an essential gene in cancer metastasis, and upregulated the expression of the tumour-related genes HNF4 and NEUROD1 under hypoxic conditions. Since hypoxia is closely associated with cancer, the hypoxia-dependent Cas9/dCas9 system is a novel addition to the molecular tool kit that functions in response to cellular signals and has potential application for gene therapeutics.

Competitive Effects of Oxidation and Quantum Confinement on Modulation of the Photophysical Properties of Metallic-Phase Tungsten Dichalcogenide Quantum Dots.

Metallic-phase transition metal dichalcogenide quantum dots (TMDs-mQDs) have been reported in recent years. However, a dominant mechanism for modulating their intrinsic exciton behaviors has not been determined yet as their size is close to the Bohr radius. Herein, we demonstrate that the oxidation effect prevails over quantum confinement on metallic-phase tungsten dichalcogenide QDs (WX2-mQDs; X = S, Se) when the QD size becomes larger than the exciton Bohr radius. WX2-mQDs with a diameter of ~12 nm show an obvious change in their photophysical properties when the pH of the solution changes from 2 to 11 compared to changing the size from ~3 nm. Meanwhile, we found that quantum confinement is the dominant function for the optical spectroscopic results in the WX2-mQDs with a size of ~3 nm. This is because the oxidation of the larger WX2-mQDs induces sub-energy states, thus enabling excitons to migrate into the lower defect energy states, whereas in WX2-mQDs with a size comparable to the exciton Bohr radius, protonation enhances the quantum confinement.

WUSCHEL controls genotype-dependent shoot regeneration capacity in potato.

Plant cells can reprogram their fate. The combinatorial actions of auxin and cytokinin dedifferentiate somatic cells to regenerate organs, which can develop into individual plants. As transgenic plants can be generated from genetically modified somatic cells through these processes, cell fate transition is an unavoidable step in crop genetic engineering. However, regeneration capacity closely depends on the genotype, and the molecular events underlying these variances remain elusive. In the present study, we demonstrated that WUSCHEL (WUS)-a homeodomain transcription factor-determines regeneration capacity in different potato (Solanum tuberosum) genotypes. Comparative analysis of shoot regeneration efficiency and expression of genes related to cell fate transition revealed that WUS expression coincided with regeneration rate in different potato genotypes. Moreover, in a high-efficiency genotype, WUS silencing suppressed shoot regeneration. Meanwhile, in a low-efficiency genotype, regeneration could be enhanced through the supplementation of a different type of cytokinin that promoted WUS expression. Computational modeling of cytokinin receptor-ligand interactions suggested that the docking pose of cytokinins mediated by hydrogen bonding with the core residues may be pivotal for WUS expression and shoot regeneration in potatoes. Furthermore, our whole-genome sequencing analysis revealed core sequence variations in the WUS promoters that differentiate low- and high-efficiency genotypes. The present study revealed that cytokinin responses, particularly WUS expression, determine shoot regeneration efficiency in different potato genotypes.

The Distinctive Permutated Domain Structure of Periplasmic α-Amylase (MalS) from Glycoside Hydrolase Family 13 Subfamily 19.

Periplasmic α-amylase MalS (EC. 3.2.1.1), which belongs to glycoside hydrolase (GH) family 13 subfamily 19, is an integral component of the maltose utilization pathway in Escherichia coli K12 and used among Ecnterobacteriaceae for the effective utilization of maltodextrin. We present the crystal structure of MalS from E. coli and reveal that it has unique structural features of circularly permutated domains and a possible CBM69. The conventional C-domain of amylase consists of amino acids 120-180 (N-terminal) and 646-676 (C-terminal) in MalS, and the whole domain architecture shows the complete circular permutation of C-A-B-A-C in domain order. Regarding substrate interaction, the enzyme has a 6-glucosyl unit pocket binding it to the non-reducing end of the cleavage site. Our study found that residues D385 and F367 play important roles in the preference of MalS for maltohexaose as an initial product. At the active site of MalS, ß-CD binds more weakly than the linear substrate, possibly due to the positioning of A402. MalS has two Ca2+ binding sites that contribute significantly to the thermostability of the enzyme. Intriguingly, the study found that MalS exhibits a high binding affinity for polysaccharides such as glycogen and amylopectin. The N domain, of which the electron density map was not observed, was predicted to be CBM69 by AlphaFold2 and might have a binding site for the polysaccharides. Structural analysis of MalS provides new insight into the structure-evolution relationship in GH13 subfamily 19 enzymes and a molecular basis for understanding the details of catalytic function and substrate binding of MalS.

Unsaturated Fatty Acids Complex Regulates Inflammatory Cytokine Production through the Hyaluronic Acid Pathway.

In this study, we aimed to develop natural and/or functional materials with antioxidant and anti-inflammatory effects. We obtained extracts from natural plants through an oil and hot-water extraction process and prepared an extract composite of an effective unsaturated fatty acid complex (EUFOC). Furthermore, the antioxidant effect of the extract complex was evaluated, and the anti-inflammatory effect was explored by assessing its inhibitory effect on nitric oxide production through its HA-promoting effect. We conducted a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay to evaluate the cell viability of the EUFOC, and the results showed that EUFOC was not cytotoxic at the test concentrations. In addition, it showed no endogenous cytotoxicity in HaCaT (human keratinocyte) cells. The EUFOC showed excellent 1,1-diphenyl-2-picrylhydrazyl- and superoxide-scavenging abilities. Moreover, it exerted an inhibitory effect on NO production at concentrations that did not inhibit cell viability. The secretion of all the cytokines was increased by lipopolysaccharide (LPS) treatment; however, this was inhibited by the EUFOC in a concentration-dependent manner. In addition, hyaluronic acid content was markedly increased by the EUFOC in a dose-dependent manner. These results suggest that the EUFOC has excellent anti-inflammatory and antioxidant properties, and hence, it can be used as a functional material in various fields.

High-Performance Electrochromic Devices Based on Size-Controlled 2D WO3 Nanosheets Prepared Using the Intercalation Method.

It is difficult to obtain ultrathin two-dimensional (2D) tungsten trioxide (WO3) nanosheets through direct exfoliation from bulk WO3 in solution due to the strong bonding between interlayers. Herein, WO3 nanosheets with controllable sizes were synthesized via K+ intercalation and the exfoliation of WO3 powder using sonication and temperature. Because of the intercalation and expansion in the interlayer distance, the intercalated WO3 could be successfully exfoliated to produce a large quantity of individual 2D WO3 nanosheets in N-methyl-2-pyrrolidone under sonication. The exfoliated ultrathin WO3 nanosheets exhibited better electrochromic performance in an electrochromic device than WO3 powder and exfoliated WO3 without intercalation. In particular, the prepared small WO3 nanosheets exhibited excellent electrochromic properties with a large optical modulation of 41.78% at 700 nm and fast switching behavior times of 9.2 s for bleaching and 10.5 s for coloring. Furthermore, after 1000 cycles, the small WO3 nanosheets still maintained 86% of their initial performance.

Graphene Quantum Dots with Blue and Yellow Luminescence Fabricated by Modulating Intercalation State.

The development of graphene quantum dots (GQDs) with low toxicity, excellent dispersibility, and high photostability has led to extensive progress in bio-imaging and optical sensing applications. However, one-pot synthesis and mass production of GQDs, and tuning their photoluminescence, remains a challenge. Here we demonstrate a simple and scalable method for fabricating GQDs with high size uniformity and chemical stability, via a sequential process of inserting alkali metal into graphite (Stage I: KC8 and Stage II: KC24) and exfoliation to GQDs in a selected solvent. Structural and optical measurements were conducted, and the emitted colors of the as-prepared GQDs were blue (KC8) and yellow (KC24), respectively. The stage of graphite intercalation in the compounds played an important role in the size and thickness of the GQD. The as-prepared GQDs had clear characteristic peaks consistent with the quantum confinement effect and intrinsic/extrinsic states. Our approach will provide great potential for a wide variety of bioimaging and bioanalysis applications.

Potential Effect of Enzymatic Porcine Placental Hydrolysate (EPPH) to Improve Alcoholic Liver Disease (ALD) by Promoting Lipolysis in the Liver.

Alcoholic liver disease is associated with the production of highly reactive free radicals by ethanol and its metabolites. Free radicals not only induce liver oxidation and damage tissues, but also stimulate an inflammatory response in hepatocytes, leading to severe liver disease. In order to improve alcoholic liver disease, enzymatic porcine placenta hydrolysate was studied by exploring various materials. Enzymatic porcine placenta hydrolysate (EPPH) contains various amino acids, peptides, and proteins, and is used as a useful substance in the body. In this study, changes were confirmed in indicators related to the antioxidant efficacy of EPPH in vitro and in vivo. EPPH inhibits an EtOH-induced decrease in superoxide dismutase and catalase activity through inhibition of free radicals without endogenous cytotoxicity. EPPH has been observed to have a partial effect on common liver function factors such as liver weight, ALT, AST, ALP, and GGT. In addition, EPPH affected changes in fat regulators and inflammatory cytokines in blood biochemical assays. It was confirmed that EPPH was involved in fat metabolism in hepatocytes by regulating PPARα in an alcoholic liver disease animal model. Therefore, EPPH strongly modulates Bcl-2 and BAX involved in apoptosis, thereby exhibiting cytochrome P450 (CYP)-inhibitory effects in alcoholic liver disease cells. As a result, this study confirmed that EPPH is a substance that can help liver health by improving liver disease in an alcoholic liver disease animal model.

Effects of taxifolin from enzymatic hydrolysis of Rhododendron mucrotulatum on hair growth promotion.

Flavonoid aglycones possess biological activities, such as antioxidant and antidiabetic activities compared to glycosides. Taxifolin, a flavonoid aglycones, is detected only in trace amounts in nature and is not easily observed. Therefore, in this study, to investigate the hair tonic and hair loss inhibitors effect of taxifolin, high content of taxifolin aglycone extract was prepared by enzymatic hydrolysis. Taxifolin effectively regulates the apoptosis of dermal papilla cells, which is associated with hair loss, based on its strong antioxidant activities. However, inhibition of dihydrotestosterone (DHT), which is a major cause of male pattern hair loss, was significantly reduced with taxifolin treatment compared with minoxidil, as a positive control. It was also confirmed that a representative factor for promoting hair growth, IGF-1, was significantly increased, and that TGF-ß1, a representative biomarker for hair loss, was significantly reduced with taxifolin treatment. These results suggest that taxifolin from enzymatic hydrolysis of RM is a potential treatment for hair loss and a hair growth enhancer.

Hypercompact adenine base editors based on transposase B guided by engineered RNA.

Transposon-associated transposase B (TnpB) is deemed an ancestral protein for type V, Cas12 family members, and the closest ancestor to UnCas12f1. Previously, we reported a set of engineered guide RNAs supporting high indel efficiency for Cas12f1 in human cells. Here we suggest a new technology whereby the engineered guide RNAs also manifest high-efficiency programmable endonuclease activity for TnpB. We have termed this technology TaRGET (TnpB-augment RNA-based Genome Editing Technology). Having this feature in mind, we established TnpB-based adenine base editors (ABEs). A Tad-Tad mutant (V106W, D108Q) dimer fused to the C terminus of dTnpB (D354A) showed the highest levels of A-to-G conversion. The limited targetable sites for TaRGET-ABE were expanded with engineered variants of TnpB or optimized deaminases. Delivery of TaRGET-ABE also ensured potent A-to-G conversion rates in mammalian genomes. Collectively, the TaRGET-ABE will contribute to improving precise genome-editing tools that can be delivered by adeno-associated viruses, thereby harnessing the development of clustered regularly interspaced short palindromic repeats (CRISPR)-based gene therapy.