Promotion of hair growth by a conditioned medium from human umbilical cord mesenchymal stem cells cultivated in a 3D scaffold of gelatin sponge.

BACKGROUND: This study aims to investigate the effects of a conditioned medium (CM) from human umbilical cord mesenchymal stem cells (HuMSCs) cultivated in gelatin sponge (GS-HuMSCs-CM) on hair growth in a mouse model. METHODS: CM was collected from the HuMSCs cultivated in a monolayer or in a gelatin sponge. Vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), keratinocyte growth factor (KGF), and hepatocyte growth factor (HGF) levels in CMs were measured by enzyme-linked immunosorbent assays (ELISAs). A hair loss model by a C57 BL/6J mouse was prepared. The effects of GS-HuMSCs-CM and HuMSCs on hair regrowth in mice were investigated by intradermal injection in the depilated back skin with normal saline (NS) as the control. The time for hair regrowth and full covering in depilated areas was observed, and the hair growth was evaluated histologically and by grossly measuring hair length and diameter. RESULTS: Compared with monolayer cultured cells, the three-dimensional (3D) culture of HuMSCs in gelatin sponge drastically increased VEGF, IGF-1, KGF, and HGF production. GS-HuMSCs-CM and HuMSCs injection both promoted hair regeneration in mice, while GS-HuMSCs-CM presented more enhanced effects in hair length, hair diameter, and growth rate. GS-HuMSCs-CM significantly promoted angiogenesis in injected skin areas, which might also contribute to faster hair regrowth. CONCLUSION: GS-HuMSCs-CM exerted significant effects on inducing hair growth and promoted skin angiogenesis in C57BL/6J mice.

Global research trends in prediabetes over the past decade: Bibliometric and visualized analysis.

OBJECT: This study aimed to investigate global research advances and hot trends in prediabetes in the last decade based on a bibliometric analysis of publications. Publications from 2013 to 2022 were retrieved from the Web of Science Core Collection database through a topic search. With the use of CiteSpace, VOS viewer, and Bibliometrix R software packages, the number of publications, production categories, countries/regions, institutions, authors, journals, references, and keywords were comprehensively analyzed to sort out the hot spots and directions of prediabetes and predict the future research directions. A total of 13,223 papers were recruited for this study by the end of March 3, 2023. A generally increasing trend was observed in the number of annual publications. PLOS ONE (journal), USA (national), and the University of Copenhagen (institutional) published the most papers in this research area. The top 3 contributor authors were Tuomilehto Jaakko, Rathmann Wolfgang, and Peters Annette. "Intestinal microbiota" (2020-2022) was the most populated keyword in terms of intensity, and "biomarkers," "gut microbiota," and "metabolomics" were the most populated keywords in the last 3 years. "Prediabetes: a high-risk state for diabetes development-2012" was the strongest burst reference. This study summarized the research hotspots and trends in prediabetes research in the last decade. Frontier research can be found in the journal Diabetes Care and Journal of Clinical Endocrinology Metabolism. Prediabetes research focuses on preventing risk factors to reduce the prevalence of prediabetes, and current research hotspots focus on gut microbes and metabolism-related biomarkers.

Classifications of anterior segment structure of congenital corneal opacity in infants and toddlers by ultrasound biomicroscopy and slit-lamp microscopic photographs: an observational study.

BACKGROUND: The structural features have an impact on the surgical prognosis for congenital corneal opacity (CCO). The structural classification system of CCO, however, is lacking. Based on data from ultrasound biomicroscopy (UBM) findings in infants and toddlers with CCO, this research proposed a classification system for the anterior segment structure severity. METHODS: Medical records, preoperative UBM images and slit-lamp photographs of infants and toddlers diagnosed with CCO at University Third Hospital between December 2018 and June 2022 were reviewed. According to the anterior segment structural features observed in UBM images, eyes were classified as follows: U1, opaque cornea only; U2, central anterior synechia; U3, peripheral anterior synechia combined with angle closure; and U4, aniridia or lens anomaly. The opacity appearance and corneal vascularization density observed in slit-lamp photographs were assigned grades according to previous studies. The extent of vascularization was also recorded. The corresponding intraocular anomaly classifications and ocular surface lesion severity were analysed. RESULTS: Among 81 eyes (65 patients), 41 (50.6%) were right eyes, and 40 (49.4%) were left eyes. The median age at examination was 6.91 months (n = 81, 1.00, 34.00). Two (2.5%) of the 81 eyes were classified as U1, 20 (24.7%) as U2, 22 (27.2%) as U3a, 11 (13.6%) as U3b and 26 (32.1%) as U4. Bilateral CCO eyes had more severe UBM classifications (P = 0.019), more severe dysgenesis (P = 0.012) and a larger angle closure (P = 0.009). Eyes with more severe UBM classifications had higher opacity grades (P = 0.003) and vascularization grades (P = 0.014) and a larger vascularization extent (P = 0.001). Eyes with dysgenesis had higher haze grades (P = 0.012) and more severe vascularization (P = 0.003 for density; P = 0.008 for extent), while the angle closure range was related to haze grade (P = 0.013) and vascularization extent (P = 0.003). CONCLUSIONS: This classification method based on UBM and slit-lamp photography findings in the eyes of CCO infants and toddlers can truly reflect the degree of abnormality of the ocular surface and anterior segment and is correlated with the severity of ocular surface anomalies. This method might provide meaningful guidance for surgical procedure design and prognostic determinations for keratoplasty in CCO eyes.

UPLC-Q-TOF/MS based metabolite profiling and quality marker constituents screening of root, stem and rhizome extracts of Ilex asprella.

OBJECTIVE: The root of Ilex asprella (RIA) is a popular plant resource for treating inflammation-related diseases. The purpose of this study was to identify the secondary metabolites, to compare anti-inflammatory effects and to determine the quality marker components among root, stem and rhizome sections of IA. METHODS: Chemical fingerprints of stem, root and rhizome of IA was determined by high performance liquid chromatography (HPLC). A reliable method using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was established for comprehensively determining the chemical constituents of the plants. Anti-inflammatory activities of IA and its ingredients were screened by in vivo mouse ear swelling and in vitro LPS-induced release of NO from RAW264.7 cells experiments. RESULTS: Root, stem and rhizome of IA have shown high similarity in chemical fingerprints. Totally 149 compounds were characterized in IA, including triterpenoids, triterpenoid saponins, phenolic acids and lignans. 44 of them were identified based on co-occurring Mass2Motifs, including 19 unreported ones, whilst 17 were tentatively confirmed by comparison with reference compounds. No significant anti-inflammatory activity difference among root, stem and rhizome parts of IA was found. Ilexsaponin B2, protocatechualdehyde, isochlorogenic acid B and quinic acid, were screened out as quality marker compounds in IA. CONCLUSION: A sensitive and rapid strategy was established to evaluate the differences on secondary metabolites of different parts of IA for the first time, and this study may contribute to the quality evaluation of medicinal herbs and provide theoretically data support for further analysis of different parts of IA.

A New Treatment for Recalcitrant Neurotrophic Keratopathy of Ocular Graft-Versus-Host Disease with Virus Infection.

INTRODUCTION: Neurotrophic keratopathy (NK) is a rare degenerative ocular disease that can be difficult to treat. There were no effective resolutive treatments for severe NK caused by ocular graft-versus-host disease (oGVHD) along with virus infection. To address this question, we designed a prospective cohort study to evaluate the efficacy and safety of topical recombinant human nerve growth factor (rhNGF) in patients with recalcitrant NK of oGVHD and viral infection. METHODS: This prospective cohort study enrolled patients with recalcitrant NK diagnosed with oGVHD and treated with rhNGF. Clinical evaluations included the range of epithelial defects, best corrected visual acuity, intraocular pressure, slit-lamp examination, and corneal fluorescein staining. Examinations of the central corneal thickness, corneal sensitivity, and nerve fiber regeneration were performed at each visit at 4, 8, 12, 20 weeks and 6 months, respectively, after initiating rhNGF treatment. RESULTS: All enrolled patients were diagnosed with NK at stage 2 (7 eyes, 63.6%) or stage 3 (4 eyes, 36.4%) and responded to rhNGF treatment. Five of 11 (45.5%) and 9 of 11 eyes (81.8%) achieved complete corneal epithelial healing after 4 and 8 weeks, respectively. All 11 eyes (100%) achieved complete corneal healing after 12 weeks. There was also a significant reduction in the corneal ulcer area during each visit (P < 0.001), as well as in the corneal fluorescein staining score (P < 0.010). There was a significant improvement in corneal sensation when compared to the baseline (P < 0.050). CONCLUSION: Topical treatment with rhNGF effectively promoted the complete corneal healing of persistent epithelial defects and corneal ulcers in patients with recalcitrant NK in oGVHD and viral infection.

Enhanced adsorption for trivalent antimony by nano-zero-valent iron-loaded biochar: performance, mechanism, and sustainability.

The discharge of tailing leachate and metallurgical wastewater has led to an increasing trend of water pollution. In this study, nZVI-modified low-temperature biochar was used to adsorb Sb(III) from water. The adsorption capacity and speed of nZVI-BC were better than those of BC, and the best adsorption effect was observed for 4nZVI-BC, with 93.60 mg·g-1 maximum adsorptive capacity, which was 208.61% higher than the original BC. The Langmuir and Temkin models were well fitted (R2 ≥ 0.99), and PSO was more in line with the 4nZVI-BC adsorption process, indicating that the adsorption was a monolayer physico-chemical adsorption. The combination of XRD, FTIR, and XPS characterization demonstrated that the adsorption mechanism predominantly included redox reactions, complexation, and electrostatic interactions. The thermodynamic results demonstrated that 4nZVI-BC adsorption on Sb(III) was a spontaneous endothermic process. Additionally, the order of the influence of interfering ions on 4nZVI-BC was CO32- > H2PO4- > SO42- > Cl-. After three repeated uses and adsorption-desorption, the adsorption ratio of Sb(III) by 4nZVI-BC was still as high as 90% and 65%, respectively. This study provides a theoretical reference for the exploration and development of Sb(III) removal technologies for aquatic environments.

Membrane mechanics dictate axonal morphology and function.

Axons are thought to be ultrathin membrane cables of a relatively uniform diameter, designed to conduct electrical signals, or action potentials. Here, we demonstrate that unmyelinated axons are not simple cylindrical tubes. Rather, axons have nanoscopic boutons repeatedly along their length interspersed with a thin cable with a diameter of ∼60 nm like pearls-on-a-string. These boutons are only ∼200 nm in diameter and do not have synaptic contacts or a cluster of synaptic vesicles, hence non-synaptic. Our in silico modeling suggests that axon pearling can be explained by the mechanical properties of the membrane including the bending modulus and tension. Consistent with modeling predictions, treatments that disrupt these parameters like hyper- or hypo-tonic solutions, cholesterol removal, and non-muscle myosin II inhibition all alter the degree of axon pearling, suggesting that axon morphology is indeed determined by the membrane mechanics. Intriguingly, neuronal activity modulates the cholesterol level of plasma membrane, leading to shrinkage of axon pearls. Consequently, the conduction velocity of action potentials becomes slower. These data reveal that biophysical forces dictate axon morphology and function and that modulation of membrane mechanics likely underlies plasticity of unmyelinated axons.

Axenfeld-Rieger syndrome: a novel histopathologic finding associated with corneal abnormalities.

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is a rare kind of anterior segment dysgenesis (ASD). The most common ocular features of ARS are posterior embryotoxon and iris hypoplasia, while some patients may manifest as corneal opacity and edema. However, the current understanding of how ARS affects the cornea is still incomplete. This study reports a novel histopathological finding of ARS, complicating corneal abnormalities, including congenital corneal opacity and irreversible endothelial decompensation. METHODS: This retrospective study included 6 eyes of 3 ARS patients, 5 of which underwent keratoplasty for irreversible endothelial decompensation from May 2016 to January 2019. No eye had a history of surgery. We reviewed the data of epidemiology, clinical manifestations and histopathologic examinations. RESULTS: Five eyes developed irreversible endothelial decompensation, among which 4 were born with corneal opacity. One eye exhibited transparent cornea but showed a continuous loss of endothelial cells in the absence of surgery and elevated intraocular pressure thereafter. Anterior segment optical coherence tomography photographs showed that anterior synechia existed in the area with corneal opacities, where we found the interlayer splitting of the Descemet membrane inserted by hypoplastic iris and a basement membrane-like structure under a light microscope. CONCLUSION: Anterior synechia might be associated with corneal abnormalities in ARS patients. The novel histopathologic finding revealed the internal relation between anterior segment dysgenesis and would help explore the inner mechanism of corneal abnormalities in ARS.

Construction of a Nanorod Structure-Confined Pt@CeO2 Catalyst by an In-Situ Encapsulation Strategy for Low-Temperature Catalytic Oxidation of Toluene.

In this work, Pt@CeO2 catalysts with a nanorod structure (Pt@CeO2 -R) and a bunch structure (Pt@CeO2 -B) were synthesized through an in-situ encapsulation strategy of Pt species in Ce-MOFs, respectively. It was discovered that the Pt@CeO2 -R catalyst possessed the best catalytic performance for toluene catalytic combustion, and this result was mainly caused by the confinement of Pt nanoparticles in Ce-MOFs, which was related to the chemical state of Pt species, redox ability, and the amount of active oxygen species. The Pt@CeO2 -R catalyst contained more Ce3+ species, rich Pt4+ species, and abundant active oxygen species due to the existence of the confined effect, which was conducive to promote catalytic oxidation of toluene. In addition, the Pt@CeO2 -R catalyst also exhibited more redox ability, which may speed up the catalytic reaction rates. On the contrary, the Pt/CeO2 -R catalyst was synthesized through a simple impregnation method and exhibited the poor activity for toluene catalytic combustion due to poor Pt4+ species and active oxygen species. Therefore, this work provides a feasible experimental basis for the study of different morphologies and encapsulated metal nanoparticles.

Quantification of Increased Corneal Subbasal Nerve Tortuosity in Dry Eye Disease and Its Correlation With Clinical Parameters.

Purpose: This study quantified corneal subbasal nerve tortuosity in dry eye disease (DED) and investigated its correlation with clinical parameters by proposing an aggregated measure of tortuosity (Tagg). Methods: The sample consisted of 26 eyes of patients with DED and 23 eyes of healthy volunteers, which represented separately the dry eye group and the control group. Clinical evaluation of DED and in vivo confocal microscopy analysis of the central cornea were performed. Tagg incorporated six metrics of tortuosity. Corneal subbasal nerve images of subjects and a validation data set were analyzed using Tagg. Spearman's rank correlation was performed on Tagg and clinical parameters. Results: Tagg was validated using 1501 corneal nerve images. Tagg was higher in patients with DED than in healthy volunteers (P < 0.001). Tagg was positively correlated with the ocular surface disease index (r = 0.418, P = 0.003) and negatively correlated with tear breakup time (r = -0.398, P = 0.007). There was no correlation between Tagg and visual analog scale scores, corneal fluorescein staining scores, or the Schirmer I test. Conclusions: Tagg was validated for quantification of corneal subbasal nerve tortuosity and was higher in patients with DED than in healthy volunteers. A higher Tagg may be linked to ocular discomfort, visual function disturbance, and tear film instability. Translational Relevance: Corneal subbasal nerve tortuosity is a potential biomarker for corneal neurobiology in DED.

Global prevalence of hepatitis C virus in children in 2018: a modelling study.

BACKGROUND: Hepatitis C virus (HCV) prevalence estimates for adults and high-risk groups have been widely published, but the disease burden in children is poorly understood. Direct-acting antiviral drugs, which are considered to be highly effective curative therapies for HCV, are now approved for paediatric patients as young as 3 years. Reliable prevalence estimates for this population are needed to inform scale-up of treatment and national strategies. This analysis combines past modelling and epidemiological work in 104 countries and territories to estimate global HCV prevalence in children in 2018. METHODS: In this modelling study, a comprehensive literature review for articles published between Jan 1, 2000, and March 31, 2019, was used to determine historical HCV prevalence estimates in children in all 249 countries and territories of the world. We identified published HCV prevalence estimates for children aged 0-18 years who are not at high risk of HCV infection in 39 countries and territories and inputted them into dynamic Markov disease-burden models to estimate viraemic HCV prevalence in 2018. For 25 of them, which had complete data, available information on HCV prevalence in children was used to build regression models to predict paediatric prevalence in an additional 65 countries and territories that had country-specific or territory-specific data about predictors only. Regression models were created for each 5-year paediatric age cohort from 0 to 19 years, considering several predictor variables. The data and forecasts from the 104 countries and territories for which data were available were used to calculate HCV prevalence by Global Burden of Disease region, which was then applied to the remaining 145 countries and territories to generate a global estimate. FINDINGS: The global estimate for viraemic prevalence in the paediatric population aged 0-18 years was 0·13% (95% uncertainty interval 0·08-0·16), corresponding to 3·26 million (2·07-3·90) children with HCV in 2018. HCV prevalence increased with age in all countries and territories. HCV prevalence in women of childbearing age was the strongest predictor of HCV prevalence in children aged 0-4 years (p<0·0001). Prevalence of HCV in adults was significantly associated with HCV prevalence in children aged 5-19 years (p<0·0001), and the proportion of HCV infections in people who inject drugs was significantly associated with HCV prevalence in children aged 15-19 years (p=0·036). INTERPRETATION: Most studies on HCV prevalence in children focus on high-risk groups and highly endemic geographic areas. Our analysis provides global prevalence estimates of HCV in the paediatric population. Treatment in paediatric patients requires different clinical and population health management optimisation than in adults. Because of this heterogeneity, country-specific or territory-specific and age-specific HCV prevalence estimates can help countries and territories to improve national HCV elimination strategies. FUNDING: Gilead Sciences, John C Martin Foundation, and private donors.

Intraoperative monitoring of neuromuscular function with soft, skin-mounted wireless devices.

Peripheral nerves are often vulnerable to damage during surgeries, with risks of significant pain, loss of motor function, and reduced quality of life for the patient. Intraoperative methods for monitoring nerve activity are effective, but conventional systems rely on bench-top data acquisition tools with hard-wired connections to electrode leads that must be placed percutaneously inside target muscle tissue. These approaches are time and skill intensive and therefore costly to an extent that precludes their use in many important scenarios. Here we report a soft, skin-mounted monitoring system that measures, stores, and wirelessly transmits electrical signals and physical movement associated with muscle activity, continuously and in real-time during neurosurgical procedures on the peripheral, spinal, and cranial nerves. Surface electromyography and motion measurements can be performed non-invasively in this manner on nearly any muscle location, thereby offering many important advantages in usability and cost, with signal fidelity that matches that of the current clinical standard of care for decision making. These results could significantly improve accessibility of intraoperative monitoring across a broad range of neurosurgical procedures, with associated enhancements in patient outcomes.

Designing Thin, Ultrastretchable Electronics with Stacked Circuits and Elastomeric Encapsulation Materials.

Many recently developed soft, skin-like electronics with high performance circuits and low modulus encapsulation materials can accommodate large bending, stretching, and twisting deformations. Their compliant mechanics also allows for intimate, nonintrusive integration to the curvilinear surfaces of soft biological tissues. By introducing a stacked circuit construct, the functional density of these systems can be greatly improved, yet their desirable mechanics may be compromised due to the increased overall thickness. To address this issue, the results presented here establish design guidelines for optimizing the deformable properties of stretchable electronics with stacked circuit layers. The effects of three contributing factors (i.e., the silicone inter-layer, the composite encapsulation, and the deformable interconnects) on the stretchability of a multilayer system are explored in detail via combined experimental observation, finite element modeling, and theoretical analysis. Finally, an electronic module with optimized design is demonstrated. This highly deformable system can be repetitively folded, twisted, or stretched without observable influences to its electrical functionality. The ultrasoft, thin nature of the module makes it suitable for conformal biointegration.

Soft, thin skin-mounted power management systems and their use in wireless thermography.

Power supply represents a critical challenge in the development of body-integrated electronic technologies. Although recent research establishes an impressive variety of options in energy storage (batteries and supercapacitors) and generation (triboelectric, piezoelectric, thermoelectric, and photovoltaic devices), the modest electrical performance and/or the absence of soft, biocompatible mechanical properties limit their practical use. The results presented here form the basis of soft, skin-compatible means for efficient photovoltaic generation and high-capacity storage of electrical power using dual-junction, compound semiconductor solar cells and chip-scale, rechargeable lithium-ion batteries, respectively. Miniaturized components, deformable interconnects, optimized array layouts, and dual-composition elastomer substrates, superstrates, and encapsulation layers represent key features. Systematic studies of the materials and mechanics identify optimized designs, including unusual configurations that exploit a folded, multilayer construct to improve the functional density without adversely affecting the soft, stretchable characteristics. System-level examples exploit such technologies in fully wireless sensors for precision skin thermography, with capabilities in continuous data logging and local processing, validated through demonstrations on volunteer subjects in various realistic scenarios.

Two Hydroxyproline Galactosyltransferases, GALT5 and GALT2, Function in Arabinogalactan-Protein Glycosylation, Growth and Development in Arabidopsis.

Hydroxyproline-O-galactosyltransferase (GALT) initiates O-glycosylation of arabinogalactan-proteins (AGPs). We previously characterized GALT2 (At4g21060), and now report on functional characterization of GALT5 (At1g74800). GALT5 was identified using heterologous expression in Pichia and an in vitro GALT assay. Product characterization showed GALT5 specifically adds galactose to hydroxyproline in AGP protein backbones. Functions of GALT2 and GALT5 were elucidated by phenotypic analysis of single and double mutant plants. Allelic galt5 and galt2 mutants, and particularly galt2 galt5 double mutants, demonstrated lower GALT activities and reductions in ß-Yariv-precipitated AGPs compared to wild type. Mutant plants showed pleiotropic growth and development phenotypes (defects in root hair growth, root elongation, pollen tube growth, flowering time, leaf development, silique length, and inflorescence growth), which were most severe in the double mutants. Conditional mutant phenotypes were also observed, including salt-hypersensitive root growth and root tip swelling as well as reduced inhibition of pollen tube growth and root growth in response to ß-Yariv reagent. These mutants also phenocopy mutants for an AGP, SOS5, and two cell wall receptor-like kinases, FEI1 and FEI2, which exist in a genetic signaling pathway. In summary, GALT5 and GALT2 function as redundant GALTs that control AGP O-glycosylation, which is essential for normal growth and development.