FTO-mediated SMAD2 m6A modification protects cartilage against Osteoarthritis.

N6-methyladenosine (m6A) modification is one of the most prevalent forms of epigenetic modification and plays an important role in the development of degenerative diseases such as osteoarthritis (OA). However, the evidence concerning the role of m6A modification in OA is insufficient. Here, m6A modification was increased in human OA cartilage and degenerated chondrocytes. Among all of the m6A enzymes, the expression of the demethylase fat mass and obesity-associated protein (FTO) decreased dramatically. Conditional knockout of FTO in chondrocytes accelerates OA progression. FTO transcription is regulated by runt-related transcription factor-1 (RUNX1). Reduced FTO elevates m6A modification at the adenosine N6 position in SMAD family member 2 (SMAD2) mRNA, whose stability is subsequently modulated by the recruited m6A reader protein YTH N6-methyladenosine RNA binding protein F2 (YTHDF2). Collectively, these findings reveal the function and mechanism of the m6A family member FTO in OA progression. Therefore, reducing m6A modification to increase SMAD2 stability by activating FTO might be a potential therapeutic strategy for OA treatment.

Light-emitting diode irradiation at 590 nm combined with active substances modulates ultraviolet B radiation-induced keratinocyte inflammation.

To evaluate the efficacy of yellow light-emitting diode (LED) irradiation at 590 nm, alone or in combination with anti-inflammatory active substances against ultraviolet (UV)-induced inflammation in keratinocytes. HaCaT keratinocytes were pretreated with LED yellow light (590 nm) alone or in combination with an antiinflammatory active substance such as glycerophosphoinositol choline (GC), extract of grains of paradise (Aframomum melegueta Schum, AM), or a bisabolol and ginger root extract mixture (Bb-GE) before UVB irradiation. Following each treatment, we measured the levels of inflammatory mediators secreted by keratinocytes. HaCaT keratinocytes treated with UVB (300 mJ cm-²) and then cultured for 24 h exhibited significantly upregulated expression of proinflammatory factors, including interleukin (IL)-1α, prostaglandin E2 (PGE2), and IL-8. After pretreatment with 590 nm LED, UVB-induced inflammatory responses were significantly inhibited. Co-pretreatment with 590 nm LED irradiation and GC further inhibited the expression of IL-1α and IL-8. IL-8 expression was inhibited by co-pretreatment with 590 nm LED irradiation and AM, whereas PGE2 expression was inhibited by co-pretreatment with 590 nm LED irradiation and Bb-GE. Co-treatment with 590 nm LED irradiation and various active substances modulated UVB-induced inflammation in keratinocytes, suggesting the potential application of this approach to prevent damage caused by voluntary sun exposure in daily life.

Deformation-induced grain boundary segregation in a powder-metallurgy ultrafine-grained MoNbTaTiV refractory high-entropy alloy.

A powder-metallurgy MoNbTaTiV refractory high-entropy alloy synthesized by mechanical alloying (MA) and spark plasma sintering was subjected to hot deformations at different temperatures and strain rates. The microstructural morphologies were characterized, and component element segregation was elucidated. With grain refinement and lattice strain increase, the large inhomogeneous milled powder became refined and homogeneous after the MA. Component element segregation was observed at relatively low deformation temperatures and high strain rates. As the deformation temperature increased and the strain rate decreased, the segregation gradually disappeared, which was attributed to dislocation movement.

A Machine Learning Approach for Efficiently Predicting Polymer Aging from UV-Vis Spectra.

This research has introduced an innovative approach that proficiently forecasts the alterations in ultraviolet-visible spectroscopy (UV-Vis) of polymer solutions during the aging effect. This method combines readily accessible feature descriptors with classical machine learning (ML) algorithms. Traditional spectral measurements, while precise in analyzing physical properties, are limited by their cost and efficiency. Therefore, this paper introduces a method that utilizes wavelength and the blue (B), green (G), and red (R) color values of the solutions as input features. We employed seven different ML models to train on these features with 10-fold cross-validation to ensure the reliability and generalizability of our results. After comparative analysis, all of the models performed excellently. Among them, the ExtraTree model demonstrated particularly high precision and excellent predictive ability on the testing set, with a Pearson correlation coefficient (r) of 0.9859 and a mean absolute error (MAE) of 0.0457. This study offers a practical solution for the rapid and cost-effective evaluation of polymer solutions' aging effect.

The clinical impact of serum soluble CD25 levels in children with Langerhans cell histiocytosis.

OBJECTIVE: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm with inflammatory characteristics. This study aims to investigate the correlation between sCD25 levels and clinical characteristics, as well as prognosis, in pediatric LCH. METHODS: Serum sCD25 levels were measured in 370 LCH patients under 18 years old using ELISA assays. The patients were divided into two cohorts based on different treatment regimens. We further assessed the predictive value for the prognosis impact of sCD25 in a test cohort, which was validated in the independent validation cohort. RESULTS: The median serum sCD25 level at diagnosis was 3908 pg/ml (range: 231-44 000pg/ml). sCD25 level was significantly higher in multi-system and risk organ positive (MS RO+) LCH patients compared to single-system(SS) LCH patients (p < 0.001). Patients with elevated sCD25 were more likely to have involvement of risk organs, skin, lung, lymph nodes, or pituitary (all p < 0.05). sCD25 level could predict LCH progression and relapse, with an area under the ROC curve of 60.6 %. The optimal cutoff value was determined at 2921 pg/ml. Patients in the high-sCD25 group had significantly worse progression-free survival compared to those in the low-sCD25 group (p < 0.05). CONCLUSION: Elevated serum sCD25 level at initial diagnosis was associated with high-risk clinical features and worse prognosis. sCD25 level can predict the progression/recurrence of LCH following first-line chemotherapy.

Decreased NETosis-related regulators in neuromyelitis optica spectrum disorders after plasma exchange.

OBJECTIVES: To investigate the impact of plasma exchange (PLEX) on NETosis-related regulators and their correlation with neurological improvement in NMOSD patients. METHODS: Twelve aquaporin-4 antibodies seropositive NMOSD patients were enrolled. NETosis-related regulators (myeloperoxidase [MPO], citrullinated histone H3 [CIT-H3], peptidyl arginine deiminase 4 [PAD4], neutrophil elastase [NE], CD64), pro-inflammatory cytokines (IL-1, IL-6, IL-12, TNF-α) and anti-inflammatory cytokines (IL-10, TGF-ß1) were quantitatively assessed before and after PLEX treatment. Clinical assessments included expanded disability status scale (EDSS) and visual outcome scale (VOS) scores. RESULTS: Following PLEX, all patients showed symptom improvement, with 66.7 % achieving marked-to-moderate improvement (MMI) at 3 months. Key regulators, such as MPO, CIT-H3, PAD4, NE, and pro-inflammatory cytokines such as IL-1, IL-6, IL-12, and TNF-α, exhibited a statistically significant decrease immediately after the initial PLEX session (P < 0.05). Furthermore, CD64 levels demonstrated a substantial decline after the second PLEX session (P < 0.05). Conversely, the levels of anti-inflammatory cytokines, including IL-10 and TGF-ß1, displayed an ascending trend post-PLEX. In clinical relevance analysis, among patients who reached MMI, the reductions in MPO, IL-1, and IL-6 exhibited statistically significant differences when compared to patients in the mild-to-no improvement group (P < 0.05). Pearson correlation analysis revealed that the percentage reduction in IL-6 levels after PLEX was positively correlated with the percentage reduction in patient EDSS/VOS scores (r = 0.638, P < 0.05). CONCLUSIONS: This study highlights that reduced levels of NETosis-related regulators after PLEX contribute to clinical improvement, suggesting the potential involvement of NETosis in the acute neurological impairment observed in NMOSD.

Cancer cell-intrinsic biosynthesis of itaconate promotes tumor immunogenicity.

The Krebs cycle byproduct itaconate has recently emerged as an important metabolite regulating macrophage immune functions, but its role in tumor cells remains unknown. Here, we show that increased tumor-intrinsic cis-aconitate decarboxylase (ACOD1 or CAD, encoded by immune-responsive gene 1, Irg1) expression and itaconate production promote tumor immunogenicity and anti-tumor immune responses. Furthermore, we identify thimerosal, a vaccine preservative, as a specific inducer of IRG1 expression in tumor cells but not in macrophages, thereby enhancing tumor immunogenicity. Mechanistically, thimerosal induces itaconate production through a ROS-RIPK3-IRF1 signaling axis in tumor cells. Further, increased IRG1/itaconate upregulates antigen presentation-related gene expression via promoting TFEB nuclear translocation. Intratumoral injection of thimerosal induced itaconate production, activated the tumor immune microenvironment, and inhibited tumor growth in a T cell-dependent manner. Importantly, IRG1 deficiency markedly impaired tumor response to thimerosal treatment. Furthermore, itaconate induction by thimerosal potentiates the anti-tumor efficacy of adoptive T-cell therapy and anti-PD1 therapy in a mouse lymphoma model. Hence, our findings identify a new role for tumor intrinsic IRG1/itaconate in promoting tumor immunogenicity and provide a translational means to increase immunotherapy efficacy.

Chemoselective Construction of Polycyclic Heterocycles Containing a [6-6-5] or [7-6-5] Tricyclic Core Skeleton from a 2-Isocyanophenyl Propargylic Ester.

Functionalized isocyanide chemistry represents an important research area in organic synthesis. A structurally unique 2-isocyanophenl propargylic ester has been designed to incorporate the reactivity of isocyanide and propargylic ester. Thus, the reaction of 2-isocyanophenyl propargylic ester and 2-aminoaromatic aldimine facilitates the synthesis of a wide range of polycyclic benzo[b]indolo[3,2-h][1,6]naphthyridine derivatives. Furthermore, reacting with 2-hydroxyaromatic aldimine enables the divergent synthesis of both the aforementioned scaffolds and another structurally distinctive diazabenzo[f]naphtho[2,3,4-ij]azulenes featuring a [7-6-5] core skeleton. Experimental results and DFT calculations suggest that these transformations likely proceed via the in situ generation of a strained cyclopropen-imine species followed by [3+2] cycloaddition. Next, switchable nucleophilic attack/ring-expansion/aromatization and nucleophilic addition/ring-expansion/elimination account for the observed selectivity.

The role of neutrophil and LDL-C levels in predicting intracranial hemorrhage following endovascular thrombectomy in patients with acute ischemic stroke.

OBJECTIVES: To investigate the association between intracranial hemorrhage (ICH) and preoperative levels of neutrophils and low-density lipoprotein-cholesterol (LDL-C) in acute ischemic stroke (AIS) patients following endovascular thrombectomy (EVT), and to assess the predictive value of preoperative levels of neutrophils and LDL-C. METHODS: A retrospective analysis was performed on the clinical records of patients diagnosed with AIS who underwent EVT at Nanchong Central Hospital between 2019 and 2023. Multivariate regression analysis was employed to examine the association of preoperative levels of neutrophils and LDL-C with the occurrence of ICH. Furthermore, a receiver operating characteristic curve was constructed to assess the predictive efficacy of these parameters. RESULTS: A total of 300 patients with a mean age of 68.0 years (standard deviation, 11.1 years) and a median baseline National Institutes of Health Stroke scale (NIHSS) score of 15.5 (interquartile range, 12.0-19.75) were identified in this cohort. Of these, 28 (9.3%) patients experienced ICH. Multivariate regression analysis revealed that elevated preoperative neutrophil (odds ratio [OR] 1.23, 95% confidence interval [CI] 1.10-1.38, P < 0.001) and LDL-C (OR 2.64, 95% CI 1.52-4.58, P < 0.001) levels were independently associated with ICH. The combined indicator demonstrated a higher area under the curve (AUC 0.759, 95% CI 0.654-0.865) compared with preoperative neutrophil (AUC 0.647, 95% CI 0.532-0.763) and LDL-C (AUC 0.711, 95% CI 0.607-0.814) levels individually.The specificity and sensitivity of the combined indicator were 67.9% and 83.1%, respectively. CONCLUSIONS: Preoperative levels of neutrophils and LDL-C may serve as predictive indicators for ICH in patients with AIS who have undergone EVT; moreover, the combination of preoperative neutrophil and LDL-C levels demonstrates enhanced predictive efficacy.

Development and validation of a perivascular space segmentation method in multi-center datasets.

BACKGROUND: Perivascular spaces (PVS) visible on magnetic resonance imaging (MRI) are significant markers associated with various neurological diseases. Although quantitative analysis of PVS may enhance sensitivity and improve consistency across studies, the field lacks a universally validated method for analyzing images from multi-center studies. METHODS: We annotated PVS on multi-center 3D T1-weighted (T1w) images acquired using scanners from three major vendors (Siemens, General Electric, and Philips). A neural network, mcPVS-Net (multi-center PVS segmentation network), was trained using data from 40 subjects and then tested in a separate cohort of 15 subjects. We assessed segmentation accuracy against ground truth masks tailored for each scanner vendor. Additionally, we evaluated the agreement between segmented PVS volumes and visual scores for each scanner. We also explored correlations between PVS volumes and various clinical factors such as age, hypertension, and white matter hyperintensities (WMH) in a larger sample of 1020 subjects. Furthermore, mcPVS-Net was applied to a new dataset comprising both T1w and T2-weighted (T2w) images from a United Imaging scanner to investigate if PVS volumes could discriminate between subjects with differing visual scores. We also compared the mcPVS-Net with a previously published method that segments PVS from T1 images. RESULTS: In the test dataset, mcPVS-Net achieved a mean DICE coefficient of 0.80, with an average Precision of 0.81 and Recall of 0.79, indicating good specificity and sensitivity. The segmented PVS volumes were significantly associated with visual scores in both the basal ganglia (r = 0.541, p < 0.001) and white matter regions (r = 0.706, p < 0.001), and PVS volumes were significantly different among subjects with varying visual scores. Segmentation performance was consistent across different scanner vendors. PVS volumes exhibited significant associations with age, hypertension, and WMH. In the United Imaging scanner dataset, PVS volumes showed good associations with PVS visual scores evaluated on either T1w or T2w images. Compared to a previously published method, mcPVS-Net showed a higher accuracy and improved PVS segmentation in the basal ganglia region. CONCLUSION: The mcPVS-Net demonstrated good accuracy for segmenting PVS from 3D T1w images. It may serve as a useful tool for future PVS research.

Less is more: CRISPR/Cas9-based mutations in DND1 gene enhance tomato resistance to powdery mildew with low fitness costs.

Powdery mildew (PM), triggered by Oidium neolycopersici, represents a significant threat and a major concern for the productivity of tomato plants (Solanum lycopersicum L.). The presence of susceptibility (S) genes in plants facilitates pathogen proliferation and their dysfunction can lead to a recessively inherited broad-spectrum and durable type of resistance. Past studies have demonstrated that disrupting the function of DND1 (Defense No Death 1) increases plant resilience against various pathogens, such as powdery mildew (PM), but this comes at the cost of negatively affecting the overall health and vigor of the plant. To investigate the possibility of minimizing the adverse effects of the dnd1 mutation while boosting disease resistance, a CRISPR-Cas9 construct with four single guide RNAs targeting three exons of SlDND1 (Solyc02g088560.4.1) was designed and introduced into the tomato variety Moneymaker (MM) through Agrobacterium tumefaciens-mediated transformation. Three T1 lines (named E1, E3 and E4) were crossed with MM and then selfed to produce TF2 families. All the TF2 plants in homozygous state dnd1/dnd1, showed reduced PM symptoms compared to the heterozygous (DND1/dnd1) and wild type (DND1/DND1) ones. Two full knock-out (KO) mutant events (E1 and E4) encoding truncated DND1 proteins, exhibited clear dwarfness and auto-necrosis phenotypes, while mutant event E3 harbouring deletions of 3 amino acids, showed normal growth in height with less auto-necrotic spots. Analysis of the 3D structures of both the reference and the mutant proteins revealed significant conformational alterations in the protein derived from E3, potentially impacting its function. A dnd1/dnd1 TF2 line (TV181848-9, E3) underwent whole-genome sequencing using Illumina technology, which confirmed the absence of off-target mutations in selected genomic areas. Additionally, no traces of the Cas9 gene were detected, indicating its elimination through segregation. Our findings confirm the role of DND1 as an S-gene in tomato because impairment of this gene leads to a notable reduction in susceptibility to O. neolycopersici. Moreover, we provide, for the first time, a dnd1 mutant allele (E3) that exhibits fitness advantages in comparison with previously reported dnd1 mutant alleles, indicating a possible way to breed with dnd1 mutants.

Using an internet-based platform to provide online and offline healthcare services for discharged patients.

BACKGROUND: Continuing care is needed for the growing number of chronically ill patients who struggle with health problems after discharge. This study aims to elucidate the development process, functionalities, service protocols, and utilization of an Internet Plus Care (IPC) platform devised by our hospital to offer healthcare services to discharged patients. METHODS: This was a mixed study. After describing the development process, function and usage of IPC platform, we retrospectively collect data such as the general information of service recipients and service providers, service items, and service prices through the IPC platform from January 2021 to September 2023 to characterize these services. RESULTS: 69 nurses delivered a total of 788 services to 211 patients through the IPC platform. The majority of services (N = 652, 82.7%) were delivered offline, with almost half of the recipients (N = 384, 48.7%) being elderly individuals. 46.4% of nurses provided services ≥ 3 times. Furthermore, 26.5% of patients received services three or more times. Notably, patients' care requirements exhibited variations across age groups, with wound care (n = 243, 63.3%), pressure injuries care (n = 50, 13.0%), and replacement of indwelling nasogastric tubes (n = 20, 5.2%) emerging as the top three services favored by the elderly. CONCLUSIONS: The IPC platform demonstrates potential in delivering diverse health services to patients; however, the involvement of nurses and patients needs to be enhanced. It is necessary to implement relevant safeguard policies to promote the effective use of IPC platform for health management of discharged patients in the future. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: The prevalence of chronic diseases is on the rise, and patients with chronic diseases continue to struggle with health problems after discharge and require extended treatment and rehabilitation. Our study proves that IPC platform presents a promising avenue for addressing these challenges. It is anticipated that governmental authorities will undertake comprehensive policy, legislative, and medical insurance reforms to facilitate the extensive adoption of IPC platform-based services.

Transdermal delivery of botulinum toxin-A through phosphatidylcholine/cholesterol nanoliposomes for treatment of post-acne scarring.

As an acne sequela, post-acne scarring (PSA) has huge negative impact on sufferers' quality of life because of aesthetical embarrassment. Transdermal delivery of botulinum toxin-A (BTXA) is a promising strategy for PAS treatment, but currently reported approaches are far from satisfactory. In this work, phosphatidylcholine/cholesterol (PC/Chol) nanoliposomes were utilized for encapsulation and transdermal delivery of BTXA. The composition, structure, morphology, size, size distribution, etc. of as-prepared BTXA@liposome nanoparticles were investigated in detail. Simulated transdermal delivery assay indicated that the diffusion depth of the BXTA@liposome nanoparticles was nearly 8 times that of pure BTXA and reached 380 µm. 12 facial PSA patients were recruited to evaluate the curative effect of the BTXA@liposome nanoparticles on PSA. Through ECCA (échelle d'évaluation clinique des cicatrices d'acné) scoring and self-evaluation of patients, the resultant data indicated that compared to hyaluronic acid (HA) hydrogel treatment the BTXA@liposome/HA hydrogel treatment could better relieve PSA to some extent but didn't show significant advantage. Further work is needed to verify the feasibility and curative effect of this method in PSA treatment in the future.

Factors Affecting Patient Satisfaction with Double-Eyelid Blepharoplasty.

BACKGROUND: Blepharoplasty is a common surgical technique performed in individuals seeking aesthetic enhancement. Thus, it is essential to investigate the factors influencing postoperative satisfaction from the patient's perspective. In this study, patient-rated outcome measure questionnaires were used to identify the factors affecting patient satisfaction after full-incision upper blepharoplasty. METHODS: This retrospective study analyzed patients who underwent full-incision upper blepharoplasty at an outpatient clinic in China. The questionnaire responses were collected by telephone, text messaging, or email at 6 and 12 months postoperatively. RESULTS: In total, 149 questionnaires were collected. After a mean follow-up of 23.23 months, the patients' overall satisfaction rate was 89.43%. The factors that significantly affected postoperative satisfaction were the patient's education level, the source of referral to the surgeon, the patient's understanding of the surgical risks, application of a cold compress after surgery as recommended, unsatisfactory postoperative double-eyelid width, postoperative bilateral asymmetry, apparent postoperative cicatrices, and postoperative caterpillar-like appearance of the double eyelids. Education level, apparent postoperative cicatrices, and postoperative bilateral asymmetry influenced the patient's satisfaction with the surgical outcome. The patient's understanding of the surgical risks, unsatisfactory postoperative double-eyelid width, postoperative bilateral asymmetry, apparent postoperative cicatrices, and postoperative caterpillar-like appearance influenced the satisfaction of the patient's family and friends. CONCLUSIONS: Postoperative bilateral asymmetry, apparent postoperative cicatrices, and a low education level of the patient are independent factors that negatively affect patient satisfaction with the outcome of double-eyelid blepharoplasty. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Conversion of Retinoids along the Marine Food Chain Contributes to Adverse Impacts on the Spine, Liver, and Intestinal Health of the Marine Medaka (Oryzias melastigma).

Marine microalgae serve as an aquaculture bait. To enhance algal cell growth and breeding profits, high-intensity light conditions are standard for cultivating bait microalgae, potentially altering microalgal metabolite production. This research revealed that Thalassiosira pseudonana, when subjected to high-intensity light conditions, accumulated significant quantities of retinal (RAL) that transferred through the food chain and transformed into all-trans retinoic acid (atRA) in marine medaka. The study further explored the toxic effects on individual fish and specific tissues, as well as the mechanisms behind this toxicity. The accumulation of atRA in the liver, intestine, and spinal column resulted in structural damage and tissue inflammation, as well as oxidative stress. It also down-regulated the gene transcription levels of key pathways involved in immune function and growth. Furthermore, it disrupted the homeostasis of the intestinal microbial communities. The implications for wildlife and human health, which are influenced by the regulation of microalgal metabolite accumulation and their transfer via the food chain, require further investigation and could hold broader significance.

BRAF-V600E mutations in plasma and peripheral blood mononuclear cells correlate with prognosis of pediatric Langerhans cell histiocytosis treated with first-line therapy.

BACKGROUND: The clinical relevance of BRAF-V600E alleles in peripheral blood mononuclear cells (PBMCs) and the prognostic impact of the mutants in cell-free (cf) and PBMC DNAs of Langerhans cell histiocytosis (LCH) have not been fully clarified in pediatric LCH. METHODS: We retrospectively determined the levels of BRAF-V600E mutation in paired plasma and PBMC samples at the time of diagnosis of LCH. Subsequently, we performed a separate or combined analysis of the clinical and prognostic impact of the mutants. RESULTS: We assessed BRAF-V600E mutation in peripheral blood from 94 patients of childhood LCH. Our data showed that cfBRAF-V600E was related to young age, multiple-system (MS) disease, involvements of organs with high risk, increased risk of relapse, and worse progression-free survival (PFS) of patients. We also observed that the presence of BRAF-V600E in PBMCs at baseline was significantly associated with MS LCH with risk organ involvement, younger age, and disease progression or relapse. The coexisting of plasma(+)/PBMC(+) identified 36.2% of the patients with the worst outcome, and the hazard ratio was more significant than either of the two alone or neither, indicating that combined analysis of the mutation in plasma and PBMCs was more accurate to predict relapse than evaluation of either one. CONCLUSIONS: Concurrent assessment of BRAF-V600E mutation in plasma and PBMCs significantly impacted the prognosis of children with LCH. Further prospective studies with larger cohorts need to validate the results of this study.

High-Refractive-Index Cross-Linked Cyclic Olefin Polymers with Excellent Transparency via Thiol-Ene Click Reaction.

High-refractive-index polymers are important optical materials in optoelectronics. Conventional cyclic olefin polymers (COPs), possessing many excellent optical properties, are a class of highly promising optical materials; however, one of the greatest obstacles is their low refractive index of n = 1.52-1.54. Here, one efficient strategy of first incorporating high molar refraction groups, including carbazolyl and indolyl moieties, into unsaturated COPs via ring-opening metathesis polymerization (ROMP) and then introducing another high molar refraction sulfur atom by a subsequent thiol-ene click reaction is presented. The obtained cross-linked COPs bearing both an aromatic group and sulfur possess significantly higher refractive indices (n = 1.611-1.684 at 589 nm) and highly optical transparency (approximately 95%) in the range of vis-NIR. This provides a way toward potential applications of new-generation optical materials.

A Reactive Oxygen Species "Sweeper" Based on Hollow Mesopore Cerium Oxide Nanospheres for Targeted and Anti-Inflammatory Management of Osteoarthritis.

Osteoarthritis (OA) is a progressive joint disorder characterized by sustained oxidative stress, chronic inflammation, and the degradation of cartilage. Despite extensive research on nanocarrier treatment strategies, the therapeutic efficacy remains limited due to the lack of satisfactory vehicles that can simultaneously exhibit excellent ROS scavenging capabilities and high drug loading capacity for effective nonsurgical management of OA. In this work, we propose an innovative strategy utilizing hollow mesoporous cerium oxide nanospheres coated with membranes derived from apoptotic chondrocytes as a reactive oxygen species "sweeper" for targeted and anti-inflammatory therapy of OA. The developed DEX@HMCeNs@M demonstrates superior drug loading capacity, notable antioxidant properties, favorable biocompatibility, and controlled drug release. By leveraging the camouflage provided by apoptotic chondrocyte membranes, the engineered DEX@HMCeNs@M, which bear natural "eat me" signals, can effectively mimic chondrocyte apoptotic bodies within the joints, thereby enabling targeted delivery of the anti-inflammatory drug DEX and subsequent controlled release triggered by the acidic environment of OA. Both in vitro and in vivo experiments validate the enhanced therapeutic efficacy of our DEX@HMCeNs@M sweeper, which operates through a synergistic mechanism involving scavenging of ROS overproduction, inhibition of inflammation, restoration of mitochondrial damage, and reduction of chondrocyte apoptosis. These findings underscore the potential and efficiency of our developed DEX@HMCeNs@M strategy as an encouraging interventional approach for the progressive treatment of OA.

Genome-wide analysis of radish AHL gene family and functional verification of RsAHL14 in tomato.

The AT-hook motif nuclear localized (AHL) gene family is a highly conserved transcription factors involved in plant growth, development, and stress responses. However, AHLs have not been systematically analyzed in radish (Raphanus sativus). Therefore, we performed genome-wide identification and expression pattern, gene structure, and function verifications of radish AHLs. We identified 52 radish AHLs (RsAHL1-RsAHL52), which were unevenly distributed across nine chromosomes. Phylogenetic analysis showed that the RsAHLs were divided into two clades (A and B) and subdivided into three types (I, II, and III). Collinearity analysis revealed that the 52 RsAHLs produced 49 repeat events. Tissue expression profiles revealed differential expression of RsAHLs across different tissues, with higher expression observed in flower organs, particularly petals and anthers. qRT-PCR results indicated that RsAHLs responded to abscisic acid, methyl jasmonate, and abiotic stress (low and high temperatures and drought). Additionally, RsAHL14 induced a dwarf phenotype in tomato plants, and RsAHL14-overexpression tomato plants presented significantly decreased expression levels of the gibberellin (GA) synthetic genes ent-Copalyl diphosphatase, GA3ox-3/-4/-5, and GA20ox-1/-2/-3, but significantly increased expression of the degradation gene GA2ox-1/-3. Thus, RsAHL14 might affect plant growth by regulating GA content. Collectively, our study comprehensively identified RsAHLs in radish and provided a reference for further research on these genes.

Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis.

CONTEXT.­: Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children. OBJECTIVE.­: To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH. DESIGN.­: We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients. RESULTS.­: A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor. CONCLUSIONS.­: Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy.