Precise Laser-Modulated Anion Exchange on Ultraflexible Perovskite Films for Multicolor Patterns.

Lead halide perovskite anion exchange reactions tend to be spontaneous and rapid. To achieve precise control of anion exchange and modulate the bandgaps of perovskites to meet the demands in full-color displays, a laser-induced liquid-phase anion exchange method is developed in this paper. CsPbBr3 perovskites embedded in a polymer matrix are converted to CsPb(BrxCl1-x)3 and CsPb(BrxI1-x)3 perovskites, realizing the shift from green fluorescence to blue and red fluorescence. By changing the laser parameters, the anion exchange extent and luminescence wavelength are precisely tuned, with the maximum tuning wavelength range of 431-696 nm. Due to the focusing properties of the laser, the spatial position of anion exchange can be precisely controlled, which is significant for realizing fast and accurate patterning without masks. Based on this method, blue patterns with different light-emitting wavelengths are fabricated. RGB three-color patterns on a single perovskite composite film are successfully prepared by further replacement of halogen ions. More importantly, the polymer matrix provides ultraflexibility and good stability for the films; even if the composite films are arbitrarily folded or repeatedly bent, they can still maintain good luminous intensity. This method will show great potential in the field of flexible, full-color displays.

Continual learning for seizure prediction via memory projection strategy.

Despite extensive algorithms for epilepsy prediction via machine learning, most models are tailored for offline scenarios and cannot handle actual scenarios where data changes over time. Catastrophic forgetting(CF) for learned electroencephalogram(EEG) data occurs when EEG changes dynamically in the clinical setting. This paper implements a continual learning(CL) strategy Memory Projection(MP) for epilepsy prediction, which can be combined with other algorithms to avoid CF. Such a strategy enables the model to learn EEG data from each patient in dynamic subspaces with weak correlation layer by layer to minimize interference and promote knowledge transfer. Regularization Loss Reconstruction Algorithm and Matrix Dimensionality Reduction Algorithm are introduced into the core of MP. Experimental results show that MP exhibits excellent performance and low forgetting rates in sequential learning of seizure prediction. The forgetting rate of accuracy and sensitivity under multiple experiments are below 5%. When learning from multi-center datasets, the forgetting rates for accuracy and sensitivity decrease to 0.65% and 1.86%, making it comparable to state-of-the-art CL strategies. Through ablation experiments, we have analyzed that MP can operate with minimal storage and computational cost, which demonstrates practical potential for seizure prediction in clinical scenarios.

Long-Term Alcohol Exposure Aggravates Ischemic Stroke-Induced Damage by Promoting Pericyte NLRP3 Inflammasome Activation via Pre-Activating the TLR4/NF-κB Pathway in Rats.

Background: Ischemic stroke (IS) is one of the leading causes of death and disability in the world, and alcohol consumption has been gaining attention as an independent risk factor for IS. Blood-brain barrier (BBB) dysfunction and neuroinflammation are the core of cerebral ischemia/reperfusion (I/R) injury, and pericytes play a crucial role in the structure and function. This study is to explore the effects of long-term alcohol consumption on IS and the potential mechanisms of pericytes. Methods: Rat models of long-term alcohol intake followed by transient middle cerebral artery occlusion stroke (EtOH+tMCAO) and cell models of oxygen-glucose deprivation/reoxygenation (OGD/R) with alcohol pre-treatment were constructed. Results: Worsened infarct volume, neurological scores, and BBB disruption were observed in the EtOH+tMCAO group compared with the tMCAO group, and immunofluorescence staining showed increased pericytes NLPR3 inflammasome activation at the ischemic penumbra. In vitro, pericyte mortality and LDH release elevated pre-treated by alcohol after OGD/R, and amplified expression of NLRP3 inflammasome was detected by Western blotting and qPCR. Alcohol pre-treatment activated the TLR4/NF-κB pathway, and transfecting pericytes with TLR4-small interfering RNA (siRNA) to block TLR4 signaling markedly restrained NLRP3 inflammasome over-activation. Injecting TAK-242 in rats alleviated neurological impairment caused by alcohol. Conclusion: Long-term alcohol pre-treatment aggravated ischemic stroke-induced brain damage by activating NLRP3 inflammasome via TLR4/NF-κB signaling pathway in the pericytes.

D4-Symmetric Dirhodium Tetrakis(binaphthylphosphate) Catalysts for Enantioselective Functionalization of Unactivated C-H Bonds.

Dirhodium tetrakis(2,2'-binaphthylphosphate) catalysts were successfully developed for asymmetric C-H functionalization with trichloroethyl aryldiazoacetates as the carbene precursors. The 2,2'-binaphthylphosphate (BNP) ligands were modified by introduction of aryl and/or chloro functionality at the 4,4',6,6' positions. As the BNP ligands are C2-symmetric, the resulting dirhodium tetrakis(2,2'-binaphthylphosphate) complexes were expected to be D4-symmetric, but X-ray crystallographic and computational studies revealed this is not always the case because of internal T-shaped CH-π and aryl-aryl interactions between the ligands. The optimum catalyst is Rh2(S-megaBNP)4, with 3,5-di(tert-butyl)phenyl substituents at the 4,4' positions and chloro substituents at the 6,6' positions. This catalyst adopts a D4-symmetric arrangement and is ideally suited for site-selective C-H functionalization at unactivated tertiary sites with high levels of enantioselectivity, outperforming the best dirhodium tetracarboxylate catalyst developed for this reaction. The standard reactions were conducted with a catalyst loading of 1 mol % but lower catalyst loadings can be used if desired, as illustrated in the C-H functionalization of cyclohexane in 91% ee with 0.0025 mol % catalyst loading (29,400 turnover numbers). These studies further illustrate the effectiveness of donor/acceptor carbenes in site-selective intermolecular C-H functionalization and expand the toolbox of catalysts available for catalyst-controlled C-H functionalization.

Familial mesial temporal lobe epilepsy phenotype is associated with novel LGI1 variants: A report of two families.

OBJECTIVE: To expand the clinical phenotype and mutation spectrum of familial mesial temporal lobe epilepsy (FMTLE) and provide a new perspective for exploring the pathological mechanisms of epilepsy caused by leucine-rich glioma inactivated 1 (LGI1) variants. METHODS: We reported clinical data from two families with FMTLE and screened patients for variants in the LGI1 gene using Whole-exome sequencing and Sanger sequencing. The clinical features of FMTLE were analysed. The pathogenicity of the causative loci was assessed according to the American College of Medical Genetics and Genomics guidelines, and potential pathogenic mechanisms were predicted through multiple bioinformatics and molecular dynamics software. RESULTS: We identified two novel LGI1 truncating variants within two large families with FMTLE: LGI1 (c.1174C>T, p.Q392X) and LGI1 (c.703C>T, p.Q235X). Compared to previous reports, we found that focal to bilateral tonic-clonic seizures are a common type of seizure in FMTLE. The clinical phenotypes of patients with FMTLE caused by LGI1 variants were relatively mild, and all patients responded well to valproic acid. Bioinformatics analyses and molecular dynamics simulations showed that protein structure and interactions were considerably weakened or damaged as a result of both variants. CONCLUSION: This study presents the first report identifying LGI1 as a potential novel pathogenic gene within FMTLE families, thereby broadening the mutation spectrum associated with FMTLE. The findings of this study offer novel insights and avenues for understanding the intricate molecular mechanisms underlying LGI1 variants and their correlations with patient phenotypes. This study proposes the possibility of familial focal epilepsy syndromes overlapping.

Unraveling the chemical constituents, absorption characteristics, and metabolic profile of Codonopsis Radix based on UPLC-Q- Orbitrap MS.

Codonopsis Radix (CR), a traditional tonic medicinal material in China, has been proven to possess a variety of bioactive functions. However, its chemical composition and in vivo metabolic pattern have not been fully elucidated. In this study, AB-8 macroporous resin column chromatography was employed for the enrichment of small molecular components in CR. Furthermore, a method combining ultra-performance liquid chromatography-quadrupole-orbitrap mass spectrometry with Acquire X intelligent data acquisition technology software was developed for the preliminary screening and identification of the chemical composition of CR in vitro and their metabolites in vivo. As a result, a total of 116 components were preliminarily characterized in the CR extract, including 28 polyacetylenes, 33 organic acids, 4 amino acids, 23 alkaloids, 9 phenylpropanoids, 6 terpenoids, 2 nucleosides, and 11 others. Additionally, a total of 84 compounds, including 37 prototype components and 47 metabolites, were identified in the plasma, urine, and feces of rats after oral administration of CR. Specifically, 11, 24, 19, 32, and 25 constituents were identified in the heart, liver, spleen, lung, and kidney, respectively. Of note, the lung and spleen are the organs with the highest distribution of CR compounds. These findings will serve as valuable data for future research on the correlation between the chemical composition and pharmacological effects of CR.

Multi-frequency ultrasonic-assisted enzymatic extraction of coconut paring oil from coconut by-products: Impact on the yield, physicochemical properties, and emulsion stability.

Extraction of coconut paring oil (CPO) from processing by-products adds value to the product and reduces resource wastage. This study aims to assess the impact of 20 kHz, 20/80 kHz and 20/40/80 kHz of multi-frequency ultrasonic-assisted enzymatic extraction (MFUAEE) on the yield, physicochemical properties, fatty acid composition, total phenolic content, antioxidant activity, and emulsion stability of CPO derived from wet coconut parings (WCP). Results revealed that the CPO extraction yield with MFUAEE was 32.58 % - 43.31 % higher compared to AEE. The tri-frequency 20/40/80 kHz mode of multi-frequency ultrasound pretreatment exhibited the highest CPO extraction yield (70.08 %). The oil extracted through MFUAEE displayed similar fatty acid profiles to AEE, but had lower peroxide value, K232 and K270 values. Particularly, MFUAEE oil contained higher total phenolic content and exhibited potent DPPH free radical scavenging capacity. Results observed by SEM indicated that the pretreatment with multi-frequency ultrasound more efficiently disrupts the cellular structure of the WCP. Additionally, MFUAEE enhanced emulsion stability through the cavitation effect of ultrasound. These findings suggest that MFUAEE is a valuable approach for method for obtaining CPO with elevated extraction yield and superior quality, thereby enhancing the utilization of coconut by-products.

Outcomes comparison of elastic bandage versus lower-leg cast immobilization after anterior talofibular ligament repair.

PURPOSE: The aim of this study was to compare the clinical outcomes between patients with chronic ankle instability (CAI) undergoing arthroscopic anterior talofibular ligament (ATFL) repair who received elastic bandage treatment and those who received lower-leg cast immobilization. METHODS: CAI patients with isolated ATFL injury undergoing arthroscopic ATFL repair from January 2017 and August 2019 were included in the study. The visual analogue scale (VAS) at rest and during activities, American Orthopedic Foot and Ankle Society (AOFAS) score, Karlsson Ankle Functional Score (Karlsson score), and time of returning to walk, walk normally, work and sports were evaluated preoperatively, and at 6 months and 12 months follow-up. RESULTS: A total of 41 patients were included in this study. Among them, 24 patients accepted lower-leg cast fixation, and the other 17 patients were immobilized with elastic bandage. Compared to patients with lower-leg immobilization, patients with elastic bandage fixation had significantly lower VAS during activities (P = 0.021) and higher AOFAS score (P = 0.015) at 12 months follow-up. The Karlsson score at 6 months follow-up were significantly higher in elastic bandage group than those in lower-leg group (P = 0.011). However, no significant difference was observed in time of returning to walk, work and sports between the two groups. CONCLUSION: Elastic bandage treatment was better than lower-leg cast immobilization in terms of eliminating pain symptom at 12 months follow-up, and improving ankle functional outcome at 6 months follow-up. Moreover, the present study emphasized that lower-leg cast immobilization offered no advantages in arthroscopic ATFL repair postoperative immobilization. STUDY DESIGN: Cohort study; Level of evidence, 3.

Alloferon Mitigates LPS-Induced Endometritis by Attenuating the NLRP3/CASP1/IL-1ß/IL-18 Signaling Cascade.

Endometritis is an inflammatory reaction of the uterine lining that can lead to infertility. Alloferon, a linear non-glycosylated oligopeptide, has been recognized for its potent anti-inflammatory and immunomodulatory effects. In light of these attributes, this study aims to explore the potential therapeutic effects of alloferon in alleviating endometrial inflammation induced by lipopolysaccharide (LPS), while elucidating the underlying protective mechanisms. Two conditions representing pre- and post-menopause states were simulated using an ovariectomized (Ovx) murine model. The findings underscore alloferon's remarkable capacity to alleviate cardinal signs of endometritis, including redness, swelling, and congestion, while concurrently restoring the structural integrity of the endometrial tissue. Moreover, alloferon effectively modulates the expression of key inflammatory mediators, such as nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), cysteine aspartate-specific protease 1 (CASP1), interleukin-1ß (IL-1ß), and interleukin-18 (IL-18). In vitro experiments were conducted to further corroborate and validate these findings. In conclusion, alloferon shows promising potential in mitigating LPS-induced inflammation by attenuating the NLRP3/CASP1/IL-1ß/IL-18 signaling cascade.

Hierarchically Assembled Gigantic Fe/Co Cyanometallate Clusters Exhibiting Electron Transfer Behavior Above Room Temperature.

The construction of large and complex supramolecular architectures through self-assembly is at the forefront of contemporary coordination chemistry. Notwithstanding great success in various systems using anionic bridges (e.g., O2- or S2-) or organic ligands (e.g., pyridine or carboxylate ligands), the assembly of large cyanide-bridged clusters with increasing nuclearity remains a formidable synthetic challenge. In this study, it is achieved in preparing two heterometallic cyanometallate clusters with unprecedented complexity, [Fe20Co20] (1) and [Fe12Co15] (2), by creating the "flexibility" through a versatile ligand of bis((1H-imidazol-4-yl)methylene)hydrazine (H2L) and low-coordinate cobalt. Complex 1 features a super-square array of four cyanide-bridged [Fe4Co4] cube subunits as the corners that are interconnected by four additional [FeCo] units, resulting in a torus-shaped architecture. Complex 2 contains a lantern-like core-shell cluster with a triple-helix kernel of [Co3L3] enveloped by a [Fe12Co12] shell. The combined structure analysis and mass spectrometry study reveal a hierarchical assembly mechanism, which sheds new light on constructing cyanometallate nanoclusters with atomic precision. Moreover, complex 1 undergoes a thermally induced electron-transfer-coupled spin transition (ETCST) between the diamagnetic {FeII LS(µ-CN)CoIII LS} and paramagnetic {FeIII LS(µ-CN)CoII HS} configurations (LS = low spin, HS = high spin) above room temperature, representing the largest molecule displaying electron transfer and spin transition characteristic.

The role of metabolic reprogramming in kidney cancer.

Metabolic reprogramming is a cellular process in which cells modify their metabolic patterns to meet energy requirements, promote proliferation, and enhance resistance to external stressors. This process also introduces new functionalities to the cells. The 'Warburg effect' is a well-studied example of metabolic reprogramming observed during tumorigenesis. Recent studies have shown that kidney cells undergo various forms of metabolic reprogramming following injury. Moreover, metabolic reprogramming plays a crucial role in the progression, prognosis, and treatment of kidney cancer. This review offers a comprehensive examination of renal cancer, metabolic reprogramming, and its implications in kidney cancer. It also discusses recent advancements in the diagnosis and treatment of renal cancer.

A cross-sectional, multicenter survey of the prevalence and influencing factors for migraine in epilepsy.

OBJECTIVES: Epilepsy and migraine are common chronic neurological disease. Epidemiologic studies and shared pathophysiology and treatment suggest that these two diseases overlap. However, migraine is often underestimated among patients with epilepsy. This study aimed to evaluate the prevalence of migraine and identify the related influencing factors among adult patients with epilepsy. METHODS: Adult patients with epilepsy were recruited at the outpatient epilepsy clinic of 13 tertiary hospitals in China from February to September 2022. ID Migraine questionnaire was applied to evaluate for migraine. Both univariable and multivariable logistic regression models were used to explore the influencing factors of migraine. RESULTS: A total of 1326 patients with epilepsy were enrolled in this study. The prevalence of migraine among patients with epilepsy was 19.2% (254/1326). In the multivariable analysis, being female (OR = 1.451, 95% CI: 1.068-1.975; p = 0.018), focal and focal to bilateral tonic-clonic seizures (OR = 1.583, 95% CI: 1.090-2.281; p = 0.015), and current seizure attack in the last 3 months (OR = 1.967, 95% CI: 1.282-3.063; p = 0.002) were the influencing factors for migraine. However, <10% of patients with epilepsy received analgesics for migraine. SIGNIFICANCE: Approximately 20% of patients with epilepsy screened positive for migraine. Being female, focal and focal to bilateral tonic-clonic seizures, and current seizure attack in the last 3 months were the influencing factors for migraine. Neurologists should pay more attention to the screening and management of the migraine among patients with epilepsy in China. PLAIN LANGUAGE SUMMARY: Epilepsy and migraine are common chronic neurological disease with shared pathophysiological mechanisms and therapeutic options. However, migraine is often underestimated among patients with epilepsy. This multicenter study aimed to evaluate the prevalence of migraine and current status of treatment. In this study, approximately 20% of patients with epilepsy screened positive for migraine. Female, focal and focal to bilateral tonic-clonic seizures, and current seizure attack in the last 3 months were identified as independent influencing factors for migraine. Despite the high prevalence, the treatment for migraine was not optimistic, neurologists should pay more attention to the screening and management of migraine.

Prognostic factors underlying the development of drug-resistant epilepsy in patients with autoimmune encephalitis: a retrospective cohort study.

OBJECTIVE: The aim of our study was to analyze the characteristics of patients with autoimmune encephalitis (AE) to identify prognostic factors associated with the development of drug-resistant epilepsy (DRE). METHODS: In this retrospective observational cohort study, we enrolled adult patients with AE between January 2016 and December 2022. The patients were categorized into two groups based on the presence or absence of DRE at the last follow-up. The predictors of the development of DRE were investigated using logistic regression analysis. RESULTS: Among 121 AE patients, 75.2% (n = 91) experienced acute symptomatic seizures, and 29.8% (n = 36) developed DRE at the last follow-up. On multivariate regression analysis, the factors associated with DRE were antibody negativity (OR 3.628, 95% CI 1.092-12.050, p = 0.035), focal seizure (OR 6.431, 95% CI 1.838-22.508, p = 0.004), refractory status epilepticus (OR 8.802, 95% CI 2.445-31.689, p = 0.001), interictal epileptiform discharges on EEG (OR 6.773, 95% CI 2.206-20.790, p = 0.001), and T2/FLAIR hyperintensity in the limbic system (OR 3.286, 95% CI 1.060-10.183, p = 0.039). CONCLUSIONS: In this study, the risk of developing DRE was mainly observed among AE patients who were negative for antibodies or had focal seizures, refractory status epilepticus, interictal epileptiform discharges on EEG, and T2/FLAIR hyperintensity in the limbic system.

Predictive Modeling for Functional Outcomes After All-Inside Arthroscopic Anterior Talofibular Ligament Repair of Chronic Ankle Instability.

BACKGROUND: Arthroscopic anterior talofibular ligament repair (AATFLR) is a surgical strategy to treat chronic ankle instability (CAI) patients. This study identified risk factors that influenced the functional outcomes of AATFLR for CAI and developed prognostic nomogram for predicting functional outcomes in future AATFLR cases. METHODS: Patients undergoing AATFLR from January 2016 to June 2022 with at least 10 months of follow-up were included in the study. The Karlsson Ankle Functional Score (KAFS) was evaluated preoperatively and at last follow-up visit. A total of 15 potential predictors including age, sex, body mass index, side affected, time from injury to surgery, sports-related injury, osteophyte, loose bodies, distal tibiofibular syndesmosis, ATFL avulsion fracture, Outerbridge classification of osteochondral lesions, postoperative immobilization method, ambulation time, walking time, and follow-up time, were recorded. We first used univariate binary logistic regression analysis to select the potential significant prognostic features, which were then subjected to the least absolute shrinkage and selection operator (LASSO) regression algorithm for final feature selection. A nomogram based on the regression model was developed to estimate the functional outcomes of patients. Models were validated internally using bootstrapping and externally by calculating their performance on a validation cohort. RESULTS: Overall, 200 ankles fit inclusion criteria. Of these 200, a total of 185 (92.5%) ankles were eligible and divided into development (n = 121) and validation (n = 64) cohorts. Four predictors were ultimately included in the prognostic nomogram model: age, sex, sports-related injury, and postoperative immobilization method. CONCLUSION: We found in our cohort that the significant predictors of poorer functional outcomes of AATFLR were postoperative immobilization with lower-leg cast, female sex, non-sports-related ankle sprain, and increasing age. Prognostic nomograms were created.

Lipidomic studies revealing serological markers associated with the occurrence of retinopathy in type 2 diabetes.

PURPOSE: The duration of type 2 diabetes mellitus (T2DM) and blood glucose levels have a significant impact on the development of T2DM complications. However, currently known risk factors are not good predictors of the onset or progression of diabetic retinopathy (DR). Therefore, we aimed to investigate the differences in the serum lipid composition in patients with T2DM, without and with DR, and search for potential serological indicators associated with the development of DR. METHODS: A total of 622 patients with T2DM hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Xi'an JiaoTong University were selected as the discovery set. One-to-one case-control matching was performed according to the traditional risk factors for DR (i.e., age, duration of diabetes, HbA1c level, and hypertension). All cases with comorbid chronic kidney disease were excluded to eliminate confounding factors. A total of 42 pairs were successfully matched. T2DM patients with DR (DR group) were the case group, and T2DM patients without DR (NDR group) served as control subjects. Ultra-performance liquid chromatography-mass spectrometry (LC-MS/MS) was used for untargeted lipidomics analysis on serum, and a partial least squares discriminant analysis (PLS-DA) model was established to screen differential lipid molecules based on variable importance in the projection (VIP) > 1. An additional 531 T2DM patients were selected as the validation set. Next, 1:1 propensity score matching (PSM) was performed for the traditional risk factors for DR, and a combined 95 pairings in the NDR and DR groups were successfully matched. The screened differential lipid molecules were validated by multiple reaction monitoring (MRM) quantification based on mass spectrometry. RESULTS: The discovery set showed no differences in traditional risk factors associated with the development of DR (i.e., age, disease duration, HbA1c, blood pressure, and glomerular filtration rate). In the DR group compared with the NDR group, the levels of three ceramides (Cer) and seven sphingomyelins (SM) were significantly lower, and one phosphatidylcholine (PC), two lysophosphatidylcholines (LPC), and two SMs were significantly higher. Furthermore, evaluation of these 15 differential lipid molecules in the validation sample set showed that three Cer and SM(d18:1/24:1) molecules were substantially lower in the DR group. After excluding other confounding factors (e.g., sex, BMI, lipid-lowering drug therapy, and lipid levels), multifactorial logistic regression analysis revealed that a lower abundance of two ceramides, i.e., Cer(d18:0/22:0) and Cer(d18:0/24:0), was an independent risk factor for the occurrence of DR in T2DM patients. CONCLUSION: Disturbances in lipid metabolism are closely associated with the occurrence of DR in patients with T2DM, especially in ceramides. Our study revealed for the first time that Cer(d18:0/22:0) and Cer(d18:0/24:0) might be potential serological markers for the diagnosis of DR occurrence in T2DM patients, providing new ideas for the early diagnosis of DR.

A rabbit osteochondral defect (OCD) model for evaluation of tissue engineered implants on their biosafety and efficacy in osteochondral repair.

Osteochondral defect (OCD) is a common but challenging condition in orthopaedics that imposes huge socioeconomic burdens in our aging society. It is imperative to accelerate the R&D of regenerative scaffolds using osteochondral tissue engineering concepts. Yet, all innovative implant-based treatments require animal testing models to verify their feasibility, biosafety, and efficacy before proceeding to human trials. Rabbit models offer a more clinically relevant platform for studying OCD repair than smaller rodents, while being more cost-effective than large animal models. The core-decompression drilling technique to produce full-thickness distal medial femoral condyle defects in rabbits can mimic one of the trauma-relevant OCD models. This model is commonly used to evaluate the implant's biosafety and efficacy of osteochondral dual-lineage regeneration. In this article, we initially indicate the methodology and describe a minimally-invasive surgical protocol in a step-wise manner to generate a standard and reproducible rabbit OCD for scaffold implantation. Besides, we provide a detailed procedure for sample collection, processing, and evaluation by a series of subsequent standardized biochemical, radiological, biomechanical, and histological assessments. In conclusion, the well-established, easy-handling, reproducible, and reliable rabbit OCD model will play a pivotal role in translational research of osteochondral tissue engineering.

Corrigendum: The possibility of clinical bonding between metal/ceramic brackets to zirconia: in vitro study.

[This corrects the article DOI: 10.3389/fbioe.2024.1354241.].

Spatiotemporal Observation of Monosodium Urate Crystals Deposition in Synovial Organoids Using Label-Free Stimulated Raman Scattering.

Gout, a common form of arthritis, is characterized by the deposition of monosodium urate (MSU) crystals in joints. MSU deposition in synovial tissues would initiate arthritis flares and recurrence, causing irreversible joint damage. However, the dynamic deposition of MSU crystals in tissues lacks experimental observation. In this study, we used chemical-specific, label-free stimulated Raman scattering (SRS) microscopy to investigate the spatiotemporal deposition and morphological characteristics of MSU crystals in human synovial organoids. Our findings revealed a critical 12-h window for MSU deposition in the lining layer of gouty synovium. Moreover, distinctive inflammatory reactions of the lining and sublining synovial layers in gout using SRS microscopy were further verified by immunofluorescence. Importantly, we identified a crucial proinflammatory role of sublining fibroblast-like synoviocytes, indicating a need for targeted medication treatment on these cells. Our work contributes to the fundamental understanding of MSU-based diseases and offers valuable insights for the future development of targeted gout therapies.

Attention deficit hyperactivity disorder in children with epilepsy: a multicenter cross-sectional analysis in China.

BACKGROUND: The diagnosis and treatment of attention deficit hyperactivity disorder (ADHD) comorbid with epilepsy have been insufficiently addressed in China. We conducted a study in China to investigate the current status, diagnosis, and treatment of ADHD in children to further our understanding of ADHD comorbid with epilepsy, strengthen its management, and improve patients' quality of life. METHODS: We carried out a multicenter cross-sectional survey of children with epilepsy across China between March 2022 and August 2022. We screened all patients for ADHD and compared various demographic and clinical factors between children with and without ADHD, including gender, age, age at epilepsy onset, duration of epilepsy, seizure types, seizure frequency, presence of epileptiform discharges, and treatment status. Our objective was to explore any possible associations between these characteristics and the prevalence of ADHD. RESULTS: Overall, 395 epilepsy patients aged 6-18 years were enrolled. The age at seizure onset and duration of epilepsy ranged from 0.1-18 to 0.5-15 years, respectively. Focal onset seizures were observed in 212 (53.6%) patients, while 293 (76.3%) patients had epileptiform interictal electroencephalogram (EEG) abnormalities. Among the 370 patients treated with anti-seizure medications, 200 (54.1%) had monotherapy. Although 189 (47.8%) patients had ADHD, only 31 received treatment for it, with the inattentive subtype being the most common. ADHD was more common in children undergoing polytherapy compared to those on monotherapy. Additionally, poor seizure control and the presence of epileptiform interictal EEG abnormalities may be associated with a higher prevalence of ADHD. CONCLUSIONS: While the prevalence of ADHD was higher in children with epilepsy than in normal children, the treatment rate was notably low. This highlights the need to give more importance to the diagnosis and treatment of ADHD in children with epilepsy.

Oxidized mitochondrial DNA activates the cGAS-STING pathway in the neuronal intrinsic immune system after brain ischemia-reperfusion injury.

In the context of stroke and revascularization therapy, brain ischemia-reperfusion injury is a significant challenge that leads to oxidative stress and inflammation. Central to the cell's intrinsic immunity is the cGAS-STING pathway, which is typically activated by unusual DNA structures. The involvement of oxidized mitochondrial DNA (ox-mtDNA)-an oxidative stress byproduct-in this type of neurological damage has not been fully explored. This study is among the first to examine the effect of ox-mtDNA on the innate immunity of neurons following ischemia-reperfusion injury. Using a rat model of transient middle cerebral artery occlusion and a cellular model of oxygen-glucose deprivation/reoxygenation, we have discovered that ox-mtDNA activates the cGAS-STING pathway in neurons. Importantly, pharmacologically limiting the release of ox-mtDNA into the cytoplasm reduces inflammation and improves neurological functions. Our findings suggest that targeting ox-mtDNA release may be a valuable strategy to attenuate brain ischemia-reperfusion injury following revascularization therapy for acute ischemic stroke.