Bioinspired Wearable Hydrogel Composite with Sustained Drug-Release for Wound Healing and Naked-Eye Visual Early Warning of Wound Dehiscence.

Wound healing is critical to the structural and functional restoration of damaged tissue. However, effective wound closure and healing are always great challenges in regenerative engineering. This study provided bioinspired wearable hydrogel composites with drug-releasing hydrogel and nonclose-packed photonic crystals (NPCs) for wound therapy and naked-eye visual early warning of wound dehiscence. Molecular dynamics models and drug-releasing results illustrated the sustained drug release of ibuprofen, and the mechanical properties of the drug-releasing hydrogel were optimized with 1410% tensile strain by introducing fish collagen; their biocompatibility and adhesion were also improved. The structural color of the NPCs blue-shifted from 630 to 500 nm with 15.0% strain, and the original color was customized with poly(methyl methacrylate) (PMMA) concentration and acrylamide content. Compared with the gauze and the traditional hydrogels, the composite provided a moist environment and an effectively closed wound; the debridement and released drug avoided inflammation, and the rat wound was healed 40.5% on the third day and essentially 100% on the 14th day. The work provided a novel strategy for wound healing and naked-eye visual early warning when a wound deforms, which is expected to promote the synergistic development of clinical treatment and visualized early warning.

The Effect of α-Fe2O3(0001) Surface Containing Hydroxyl Radicals and Ozone on the Formation Mechanism of Environmentally Persistent Free Radicals.

The formation of environmentally persistent free radicals (EPFRs) is mediated by the particulate matter's surface, especially transition metal oxide surfaces. In the context of current atmospheric complex pollution, various atmospheric components, such as key atmospheric oxidants ·OH and O3, are often absorbed on particulate matter surfaces, forming particulate matter surfaces containing ·OH and O3. This, in turn, influences EPFRs formation. Here, density functional theory (DFT) calculations were used to explore the formation mechanism of EPFRs by C6H5OH on α-Fe2O3(0001) surface containing the ·OH and O3, and compare it with that on clean surface. The results show that, compared to EPFRs formation with an energy barrier on a clean surface, EPFRs can be rapidly formed through a barrierless process on these surfaces. Moreover, during the hydrogen abstraction mechanism leading to EPFRs formation, the hydrogen acceptor shifts from a surface O atom on a clean surface to an O atom of ·OH or O3 on these surfaces. However, the detailed hydrogen abstraction process differs on surfaces containing oxidants: on surfaces containing ·OH, it occurs directly through a one-step mechanism, while, on surfaces containing O3, it occurs through a two-step mechanism. But, in both types of surfaces, the essence of this promotional effect mainly lies in increasing the electron transfer amounts during the reaction process. This research provides new insights into EPFRs formation on particle surfaces within the context of atmospheric composite pollution.

ß-Hydroxybutyrate dehydrogenase functionalized two-dimensional photonic crystals for quantitative and visual sensing of ketone bodies.

ß-Hydroxybutyrate (BHB) is a substantial physiological ketone body. Its elevated concentration causes ketoacidosis, which is a disorder with a high mortality rate. Therefore, there is an urgent need to develop a simple method for the in-situ monitoring of BHB in urine. In this study, a photonic crystal hydrogel (PCH) sensing material for the detection of urinary ketones was prepared by embedding a two-dimensional polystyrene photonic crystal array (PCA) in a hydrogel functionalized with ß-hydroxybutyrate dehydrogenase (BHBDH). BHBDH catalyzes the interconversion between ß-hydroxybutyrate and acetoacetic acid and relies on the cofactor nicotinamide adenine dinucleotide (NAD+) to participate in the reaction process. The catalytic cycle of converting ß-hydroxybutyrate to acetoacetate generates H+, which reduces the electrostatic repulsion between the carboxyl groups in the hydrogel network, ultimately leading to the shrinkage of the hydrogel volume. The hydrogel volume change was detected by measuring the diameter of the Debye diffraction ring, thus reflecting the concentration of BHB. When the concentration of BHB was increased from 0 to 10 mM, the reflection spectrum of PCH shifted for 117 nm within 60 min, consequently, the structural color of PCH changed from red to green and finally to blue. The material was used for quantitative detection of BHB with a detection limit of 48.94 µM. Then it was used for detection in artificial urine samples. While, this smart and reusable sensing material could provide a more convenient and efficient strategy for the ketone body detection in clinical diagnosis and point-of-care monitoring.

Bio-Inspired Photoelectric Dual-Mode Sensor Based on Photonic Crystals for Human Motion Sensing and Monitoring.

Photoelectric dual-mode sensors, which respond to strain signal through photoelectric dual-signals, hold great promise as wearable sensors in human motion monitoring. In this work, a photoelectric dual-mode sensor based on photonic crystals hydrogel was developed for human joint motion detection. The optical signal of the sensor originated from the structural color of photonic crystals, which was achieved by tuning the polymethyl methacrylate (PMMA) microspheres diameter. The reflective peak of the sensor, based on 250 nm PMMA PCs, shifted from 623 nm to 492 nm with 100% strain. Graphene was employed to enhance the electrical signal of the sensor, resulting in a conductivity increase from 9.33 × 10-4 S/m to 2 × 10-3 S/m with an increase in graphene from 0 to 8 mg·mL-1. Concurrently, the resistance of the hydrogel with 8 mg·mL-1 graphene increased from 160 kΩ to 485 kΩ with a gauge factor (GF) = 0.02 under 100% strain, while maintaining a good cyclic stability. The results of the sensing and monitoring of finger joint bending revealed a significant shift in the reflective peak of the photoelectric dual-mode sensor from 624 nm to 526 nm. Additionally, its resistance change rate was measured at 1.72 with a 90° bending angle. These findings suggest that the photoelectric dual-mode sensor had the capability to detect the strain signal with photoelectric dual-mode signals, and indicates its great potential for the sensing and monitoring of joint motion.

Enhanced Fluorescence Based on Slow Light Effect of ZIF-8 Photonic Crystals for Trace 2,4,6-Trinitrophenol Detection.

In response to growing concerns about public safety and environmental conservation, it is essential to develop a precise identification method for trace explosives. To improve the stability and detection sensitivity of perovskite quantum dots (PQDs) and address the issue of low porosity in traditional polymer-based photonic crystals (PhCs), this study proposed a PQD photoluminescence (PL) enhancement strategy based on the slow light effect of ZIF-8 PhCs for highly sensitive, selective, and convenient detection of 2,4,6-trinitrophenol (TNP). The slow light effect at the photonic band gap edge is the basis of amplifying the PL signal. PhCs were fabricated by the evaporation-induced self-assembly method. The diffraction wavelength overlapping the whole visible region was designed to match the emission wavelength of PQDs. Results showed that PhCs matching the PBG edge with PQDs' emission peak amplified the PL signal 11.3 times, significantly improving sensitivity for trace TNP detection with a limit as low as 2.52 nM. Moreover, there was a 13.3-fold enhancement of PQDs' fluorescence lifetime when the emission wavelength fell in the PBG range. The hydrophobic surface of ZIF-8 PhCs enhanced the PQDs' stability and moisture resistance. Furthermore, the selective quenching mechanism of TNP by the sensor was photoinduced electron transfer (PET) verified by DFT calculations and time-resolved PL decay dynamics measurements. This study demonstrated great potential for manipulating light emission enhancement by PhCs in developing efficient fluorescent sensors for trace environmental pollutant detection.

Fluoride-resistant Streptococcus mutans within cross-kingdom biofilms support Candida albicans growth under fluoride and attenuate the in vitro anti-caries effect of fluorine.

Fluoride-resistant Streptococcus mutans (S. mutans) might affect the ecological balance of biofilms in the presence of fluoride. We used a S. mutans and Candida albicans (C. albicans) cross-kingdom biofilm model to investigate whether fluoride-resistant S. mutans in biofilms would support C. albicans growth under fluoride stress and attenuate the in vitro anti-caries effect of fluorine. The impact of fluoride-resistant S. mutans on formation of cross-kingdom biofilms by S. mutans and C. albicans in the presence of fluoride was investigated in vitro using the crystal violet staining assay. Biofilm constitution was determined using colony-forming unit (CFU) counts and fluorescent in situ hybridization (FISH). Extracellular polysaccharide (EPS) generation in biofilms was determined by EPS/bacterial dying and water-insoluble polysaccharide detection. Acid production and demineralization were monitored using pH, lactic acid content, and transversal microradiography (TMR). The gene expression of microorganisms in the cross-kingdom biofilm was measured using qRT-PCR. Our results showed that both C. albicans and fluoride-resistant S. mutans grew vigorously, forming robust cross-kingdom biofilms, even in the presence of sodium fluoride (NaF). Moreover, fluoride-resistant S. mutans-containing cross-kingdom biofilms had considerable cariogenic potential for EPS synthesis, acid production, and demineralization ability in the presence of NaF than fluoride-sensitive S. mutans-containing biofilms. Furthermore, the gene expression of microorganisms in the two cross-kingdom biofilms changed dissimilarly in the presence of NaF. In summary, fluoride-resistant S. mutans in cross-kingdom biofilms supported C. albicans growth under fluoride and might attenuate the anti-caries potential of fluorine by maintaining robust cross-kingdom biofilm formation and cariogenic virulence expression in vitro in the presence of NaF.

A novel dual-target Septin9 methylation assay for improved detection of early-stage colorectal cancer and high-grade intraepithelial neoplasia.

BACKGROUND: Colorectal cancer (CRC) ranks as the third most common malignancies in the world, and periodic examination of the patient is advantageous in reducing the mortality of CRC. The first blood-based Septin9 gene methylation assay which recognized by the US FDA for CRC examination was Epi proColon. However, this assay was not broadly applied in the current clinical guideline because of its relatively lower sensitivity in the detection of early-stage CRC. METHODS: This study aimed at developing a new multiplex Septin9 methylation assay (ColonUSK) which simultaneously evaluates two CpG-rich subregions in the promoter of the Septin9 gene and an internal control in a single reaction. ColonUSK proved increased sensitivity, with a detection limit as low as 12pg of the positive DNA compared with the Septin9 assay targeting one CpG-rich subregion. 1366 subjects were prospectively recruited from four comprehensive hospitals in China in an opportunistic screening study for assessing its value in CRC detection. Blind testing was developed to evaluate ColonUSK in comparison with clinical examination using clinical gold standard such as colonoscopy. RESULTS: The assay demonstrates clinical sensitivity for diagnosing colorectal cancer (CRC) and advanced adenoma at rates of 77.34% and 25.26%, respectively. Furthermore, ColonUSK exhibits a high degree of specificity for non-CRC cases (95.95%) clinically. Significantly, the detection rate of cases in high-grade intraepithelial neoplasia increased to 54.29%. The value for the assay in the Kappa test was 0.76, showing a high degree of consistency between ColonUSK and clinical gold standard. CONCLUSIONS: ColonUSK indicated moderate diagnostic value and could become a non-invasive detection way for CRC. The implementation of the ColonUSK assay has the capacity to markedly enhance CRC screening practices.

Unlocking the potential: T1-weighed MRI as a powerful predictor of levodopa response in Parkinson's disease.

BACKGROUND: The efficacy of levodopa, the most crucial metric for Parkinson's disease diagnosis and treatment, is traditionally gauged through the levodopa challenge test, which lacks a predictive model. This study aims to probe the predictive power of T1-weighted MRI, the most accessible modality for levodopa response. METHODS: This retrospective study used two datasets: from the Parkinson's Progression Markers Initiative (219 records) and the external clinical dataset from Ruijin Hospital (217 records). A novel feature extraction method using MedicalNet, a pre-trained deep learning network, along with three previous approaches was applied. Three machine learning models were trained and tested on the PPMI dataset and included clinical features, imaging features, and their union set, using the area under the curve (AUC) as the metric. The most significant brain regions were visualized. The external clinical dataset was further evaluated using trained models. A paired one-tailed t-test was performed between the two sets; statistical significance was set at p < 0.001. RESULTS: For 46 test set records (mean age, 62 ± 9 years, 28 men), MedicalNet-extracted features demonstrated a consistent improvement in all three machine learning models (SVM 0.83 ± 0.01 versus 0.73 ± 0.01, XgBoost 0.80 ± 0.04 versus 0.74 ± 0.02, MLP 0.80 ± 0.03 versus 0.70 ± 0.07, p < 0.001). Both feature sets were validated on the clinical dataset using SVM, where MedicalNet features alone achieved an AUC of 0.64 ± 0.03. Key responsible brain regions were visualized. CONCLUSION: The T1-weighed MRI features were more robust and generalizable than the clinical features in prediction; their combination provided the best results. T1-weighed MRI provided insights on specific regions responsible for levodopa response prediction. CRITICAL RELEVANCE STATEMENT: This study demonstrated that T1w MRI features extracted by a deep learning model have the potential to predict the levodopa response of PD patients and are more robust than widely used clinical information, which might help in determining treatment strategy. KEY POINTS: This study investigated the predictive value of T1w features for levodopa response. MedicalNet extractor outperformed all other previously published methods with key region visualization. T1w features are more effective than clinical information in levodopa response prediction.

Prevalence and factors associated with job burnout among nurses in China: A cross-sectional study.

AIM: Many people see nursing as a high-pressure, high-risk profession. Therefore, job burnout among nursing staff has become an important topic of study and has received widespread attention worldwide. This research intended to evaluate the frequency of and variables related with work burnout among nurses in public hospitals in China. DESIGN: Using a multistage random sample procedure, a cross-sectional survey was carried out in the eastern, central and western areas of China. METHODS: The Maslach Inventory-Human Service Survey and demographic information made up the two sections of the questionnaire. Of the 5250 questionnaires sent, 4865 were deemed legitimate, yielding an effective response rate of 92.67%. A linear regression analysis was performed to investigate the variables linked to nursing work burnout. RESULTS: Among the 4865 nurses, women accounted for 97.4% of the survey respondents, most of whom were aged 26-35 years. Results showed that the total scores of emotional exhaustion (EE), depersonalization (DP) and reduced personal accomplishment (PA) were 20.02 ± 12.04, 4.78 ± 5.54 and 34.42 ± 10.32 respectively. 50.7% of subjects obtained high or moderated scores on EE, 32.8% of subjects obtained high or moderated scores on DP and 80.4% of subjects obtained low or moderated scores on PA. Age, department, position, post-establishment, work shift type in recent months, overtime times in recent months and night shift frequency in recent months were negatively correlated with EE, and child status, monthly income, working days per week and sleep quality in recent 1 month were positively correlated with it (F = 141.827, P < 0.01, R2 = 0.243). Age, gender, department, post-establishment, overtime hours in recent months and night shift frequency in recent months were negatively correlated with DP, and child status and sleep quality in the last 1 month were positively correlated with it (F = 78.794, p < 0.01, R2 = 0.115). Child status, years of nursing work and sleep quality in the last 1 month were negatively correlated with PA, whereas age, position, work shift type in recent months and night shift frequency in recent months were positively correlated with it (F = 67.981, p < 0.01, R2 = 0.089).

A PDMS-encapsulated cylindrical non-closed-packed photonic crystals composite with Bragg-enhanced Fresnel reflectance for optical gain and spectral selection.

According to the Fresnel theory, the reflectivity intensity of spherical and cylindrical convex surfaces decreases from their edge to center, and it is noteworthy and interesting for optical gain to study the enhancement of center reflectance. In this paper, a polydimethylsiloxane (PDMS) - encapsulated cylindrical non-closed-packed photonic crystals (NPCs) composite with Bragg-enhanced Fresnel reflectance was designed for spectral selectivity and optical gain. Theoretically and experimentally, the periodically ordered structure of NPCs achieved high-reflection of light in photonic bandgap and high-transmission in other bands, which enhanced Fresnel reflectivity of the convex center to specific bands. Furtherly, the cylindrical NPCs hydrogel with stretchability was applied for the dynamic tuning of optical signals. The reflection peak of the PDMS-encapsulated cylindrical NPCs composite blue-shifted from 608 nm to 413 nm with 50 % tensile strain and achieved a rapid transition of structural color from orange to blue-violet in 60 cycles. The new kind of photonic crystals composite for optical gain and spectral selection broke through the limitations of traditional Fresnel curved mirrors with the lowest central reflectivity and inability to perform spectral selectivity, and have great significance and application prospects in fields of signal transmission, optical measurement, and instrument design.

Online Streaming Video Super-Resolution With Convolutional Look-Up Table.

Online video streaming has fundamental limitations on the transmission bandwidth and computational capacity and super-resolution is a promising potential solution. However, applying existing video super-resolution methods to online streaming is non-trivial. Existing video codecs and streaming protocols (e.g., WebRTC) dynamically change the video quality both spatially and temporally, which leads to diverse and dynamic degradations. Furthermore, online streaming has a strict requirement for latency that most existing methods are less applicable. As a result, this paper focuses on the rarely exploited problem setting of online streaming video super resolution. To facilitate the research on this problem, a new benchmark dataset named LDV-WebRTC is constructed based on a real-world online streaming system. Leveraging the new benchmark dataset, we propose a novel method specifically for online video streaming, which contains a convolution and Look-Up Table (LUT) hybrid model to achieve better performance-latency trade-off. To tackle the changing degradations, we propose a mixture-of-expert-LUT module, where a set of LUT specialized in different degradations are built and adaptively combined to handle different degradations. Experiments show our method achieves 720P video SR around 100 FPS, while significantly outperforms existing LUT-based methods and offers competitive performance compared to efficient CNN-based methods. Code is available at https://github.com/quzefan/ConvLUT.

Formation Mechanism of Environmentally Persistent Free Radicals on Alkaline Earth Oxide Surfaces.

The formation of environmentally persistent free radicals (EPFRs) is usually related to transition-metal oxides in particulate matter (PM). However, recent studies suggest that alkaline-earth-metal oxides (AEMOs) in PM also influence EPFRs formation, but the exact mechanism remains unclear. Here, density functional theory calculations were performed to investigate the formation mechanism of EPFRs by C6H5OH on AEMO (MgO, CaO, and BaO) surfaces and compare it with that on transition-metal oxide (ZnO and CuO) surfaces. Results indicate that EPFRs can be rapidly formed on AEMOs by dissociative adsorption of C6H5OH, accompanied by electrons transfer. As the alkalinity of AEMOs increases, both adsorption energy and the number of electron transfers gradually increase. Also, the stability of the formed EPFRs is mainly attributed to the electrostatic and van der Waals interactions between the phenoxy radical and surfaces. Notably, the formation mechanism of EPFRs on AEMOs is similar to that on ZnO but differs from that on CuO, as suggested through geometric structure and charge distribution analyses. This study not only elucidates the formation mechanisms of EPFRs on AEMOs but also provides theoretical insights into addressing EPFRs pollution.

Imaging, pathology, and diagnosis of solitary fibrous tumor of the pancreas: A case report and review of literature.

BACKGROUND: A solitary fibrous tumor (SFT) is often located in the pleura, while SFT of the pancreas is extremely rare. Here, we report a case of SFT of the pancreas and discuss imaging, histopathology, and immunohistochemistry for accurate diagnosis and treatment. CASE SUMMARY: A 54-year-old man presented to our hospital with pancreatic occupancy for over a month. There were no previous complaints of discomfort. His blood pressure was normal. Blood glucose, tumor markers, and enhanced computed tomography (CT) suggested a malignant tumor. Because the CT appearance of pancreatic cancer varies, we could not confirm the diagnosis; therefore, we performed endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB). Pathology and immunohistochemistry were consistent with SFT of the pancreas. The postoperative pathology and immunohistochemistry were consistent with the puncture results. The patient presented for a follow-up examination one month after discharge with no adverse effects. CONCLUSION: Other diseases must be excluded in patients with a pancreatic mass that cannot be diagnosed. CT and pathological histology have diagnostic value for pancreatic tumors. Endoscopic puncture biopsy under ultrasound can help diagnose pancreatic masses that cannot be diagnosed preoperatively. Surgery is an effective treatment for SFT of the pancreas; however, long-term follow-up is strongly recommended because of the possibility of malignant transformation of the tumor.

Intracellular Regulation Limits the Response of Intestinal Ferroportin to Iron Status in Suckling Rats.

SCOPE: Iron status is regulated via iron absorption as there is no active iron excretion. Divalent metal-ion transporter-1 (DMT1) and ferroportin (FPN) are two key proteins vital for iron absorption, but the regulation of them in suckling mammals differs from that in adults. This study aims to explore regulation of iron transporters under different iron conditions during suckling. METHODS AND RESULTS: This study developed suckling rats under different iron conditions. Unexpectedly, unchanged FPN at different iron status are detected. Since FPN is the only known iron exporter for mammals, unchanged FPN limits iron exported into blood during suckling. Thus, factors regulating FPN at transcriptional, post-transcriptional, and post-translational levels are detected. Results showed that Fpn mRNA is upregulated, while micro RNA-485(miR-485) which could silence Fpn mRNA is upregulated at low iron status limiting translation of Fpn mRNA. Besides, serum hepcidin and liver Hamp mRNA are upregulated, but ring finger protein 217( Rnf217) mRNA remained unchanged at high iron status leading to FPN not downregulated as adults. CONCLUSIONS: Overall, this study indicates that translational regulation limits intestinal FPN protein response to iron deficiency and Rnf217 cannot effectively mediate the degradation of FPN at high iron status, which provides a reference for maintaining iron homeostasis during suckling.

Naked-Eye Visual Thermometer Based on Glycerol─Nonclose-Packed Photonic Crystals for Real-Time Temperature Sensing and Monitoring.

Real-time sensing and monitoring of temperature are of great significance for assessing human health. The sensitivity and stability are inevitable issues for thermometers. In this study, a thermometer with the cylindrical thermochromic hydrogel was prepared for real-time visual monitoring of temperature, which had excellent temperature sensitivity, angle-independence axially, and environmental stability. The customization of their initial optical properties depended on the PMMA concentrations and the content of the hydrogel monomer. The glycerol introduced with solvent displacement formed hydrogen bonds with the hydrogel network, which stabilized their mechanical properties, and the reflection peak blue-shifted from 653 to 499 nm when tensile strain was 57.85%. At the same time, the environmental stability originated from the moisturizing properties of the glycerol, which enabled the hydrogel to reliably transmit the information on temperature into the air without losing moisture. The reflection peak of the cylindrical thermochromic hydrogel shifted from 657 to 455 nm when the temperature increased from 22 to 45 °C, which realized temperature visual monitoring in the full-color range. The temperature sensitivity of the glycerol─nonclose-packed photonic crystals remained stable for 1 month, which provided an optimal option for continuous visual temperature monitoring.

Hippocampal estrogens rescued the decline of synaptic plasticity after surgery and anesthesia by inhibiting microglia overactivation.

BACKGROUND: Elderly patients experience postoperative cognitive impairment frequently; therefore, effective interventions are urgently needed. Central nervous inflammation characterized by microglia may promote the progression of POCD by reducing synaptic plasticity. Notably, clinical studies revealed that the incidence of female patients was significantly lower than that of male patients. Besides, the brain estrogens have an anti-inflammatory effect and regulate the microglia at the same times. This study aimed to determine whether suppressing microglia overactivation by hippocampal estrogens can rescue the decrease of synaptic plasticity after surgery and anesthesia. METHODS: Exploratory laparotomy was used to establish the POCD model in 15-month-old male or female C57BL/6 J mice and animal behavioral tests were performed to test hippocampal-dependent memory capacity. Western blot and immunofluorescence were used to detect the microglial activation and plasticity related protein expressions. Elisa was used to detect the content of estrogens in the hippocampus. Estrogens and estrogen receptor inhibitor were used to replenish the estrogens in the brain and inhibit the effect of estrogens. RESULTS: Surgery and anesthesia did not cause POCD in female mice (P > 0.05), while the cognitive function decreased significantly after estrogen receptor inhibitor was given(P < 0.05). Male mice experienced cognitive dysfunction after surgery and anesthesia, and their cognitive function improved after estrogens supplementation (P < 0.05). Given estrogens and estrogen receptor inhibitors at the same time, the cognitive function of male mice could not be saved (P < 0.05). By correlation analysis, there was a negative correlation between the content of hippocampal estrogens and microglia (P < 0.05). The number or degree of activation of microglia affected the synaptic plasticity, which ultimately regulated the cognitive function of mice. CONCLUSION: Hippocampal estrogens rescued the decline of synaptic plasticity after surgery and anesthesia by inhibiting microglia overactivation.

Disinhibition of hippocampal parvalbumin interneurons on pyramidal neurons participates in LPS-induced cognitive dysfunction.

BACKGROUND: The vulnerability of hippocampal pyramidal (PY) neurons played a key role in the onset of cognitive impairment. Multiple researches revealed that neuroinflammation together with microglia activation and parvalbumin (PV) interneurons participated in the pathogenesis of cognitive dysfunction. However, the underlying mechanism was still unclear. This study aimed to determine whether microglia activation would induce PV interneurons impairment and PY neurons disinhibition, and as a result, promote cognitive dysfunction after lipopolysaccharide (LPS) challenge. METHODS: Male C57BL/6J mice were injected with LPS to establish systemic inflammation model, and animal behavioral tests were performed. For chemogenetics, the virus was injected bilaterally into the CA1 region. Clozapine N-Oxide (CNO) was used to activate the PV interneurons. Whole-cell patch clamp recording was applied to detect spontaneous inhibitory post synaptic current (sIPSC) and spontaneous excitatory post synaptic current (sEPSC) of PY neurons in the CA1 region. RESULTS: LPS induced hippocampal dependent memory impairment, which was accompanied with microglia activation. Meanwhile, PV protein level in hippocampus were decreased, and IPSCs of PY neurons in the CA1 were also suppressed. Minocycline reversed all the above changes. In addition, rescuing PV function with CNO improved memory impairment, sIPSCs of PY neurons and perisomatic PV boutons around PY neurons without affecting microglia activation. CONCLUSION: Disinhibition of hippocampal parvalbumin interneurons on pyramidal neurons participates in LPS-induced cognitive dysfunction.

Predictive value of remnant-like particle cholesterol in the prediction of long-term AF recurrence after radiofrequency catheter ablation.

Objective: The relationship between remnant-like particle cholesterol (RLP-C) levels and the progression of atrial fibrillation (AF) is not known. This research aimed to explore the association of RLP-C with long-term AF recurrence events post-radiofrequency catheter ablation (RFCA) of AF. Methods: In total 320 patients with AF who were subjected to the first RFCA were included in this research. Baseline information and laboratory data of patients were retrospectively collected, and a 1-year follow-up was completed. The follow-up endpoint was defined as an AF recurrence event occurring after 3 months. Afterward, a multivariate Cox regression model was constructed to analyze the risk factors that affect AF recurrence. Results: AF recurrence occurred in 103 patients (32.2%) within 3-12 months after RFCA. Based on the multivariate Cox regression analysis, Early recurrence (ER) [hazard ratio (HR) =1.57, 95% confidence interval (CI): 1.04-2.36, P = 0.032)], coronary artery disease (CAD) (HR = 2.03, 95% CI: 1.22-3.38, P = 0.006), left atrium anterior-posterior diameter (LAD) (HR = 1.07, 95% CI: 1.03-1.10, P < 0.001), triglyceride (TG) (HR = 1.51, 95% CI: 1.16-1.96, P = 0.002), low-density lipoprotein cholesterol (LDL-C) (HR = 0.74, 95% CI: 0.55-0.98, P = 0.036), and RLP-C (HR = 0.75 per 0.1 mmol/L increase, 95% CI: 0.68-0.83, P < 0.001) were linked to the risk of AF recurrence. Among them, the relationship between RLP-C and AF recurrence was found for the first time. The predictive value of RLP-C for AF recurrence was analyzed utilizing receiver operating characteristic (ROC) curves [area under the curve (AUC) = 0.81, 95% CI: 0.77-0.86, P < 0.001]. Subsequently, the optimal threshold value of RLP-C was determined to be 0.645 mmol/L with a sensitivity of 87.4% and a specificity of 63.6% based on the Youden index. Additionally, Kaplan-Meier analysis indicated a lower AF recurrence rate in the >0.645 mmol/L group than in the ≤0.645 mmol/L group (Log-rank P < 0.001). Conclusion: Low levels of RLP-C are associated with a higher risk of AF recurrence post-RFCA, suggesting that RLP-C may be a biomarker that helps to identify long-term AF recurrence.

Melatonin-mediated mitophagy protects against long-term impairments after repeated neonatal sevoflurane exposures.

BACKGROUND: Melatonin is known to have protective effects in aging, neurodegenerative disorders and mitochondria-related diseases, while there is a poor understanding of the effects of melatonin treatment on mitophagy in neonatal cognitive dysfunction after repeated sevoflurane exposures. This study explores the protective effects of melatonin on mitophagy and cognition in developing rats exposed to sevoflurane. METHODS: Postnatal day six (P6) neonatal rats were exposed to 3 % sevoflurane for 2 h daily from P6 to P8. In the intervention groups, rats received 3-Methyladenine (3-MA) intracerebroventricularly from P6 to P8 and melatonin intraperitoneally from P6 to P8 following water drinking once daily from P21 to P41, respectively. Behavioral tests, including open field (OF), novel object recognition (NOR), and fear conditioning (FC) tests, were performed to assess cognitive function during young adulthood. In another experiment, rat brains were harvested for biochemical, histopathological, and electron microscopy studies. RESULTS: Rats exposed to sevoflurane showed disordered mitophagy and mitochondrial dysfunction as revealed by increased mitophagy marker proteins (microtubule-associated protein 1 light chain 3 (LC3) II/I, and parkin), decreased autophagy marker protein (sequestosome 1 (P62/SQSTM1)), electron transport chain (ETC) proteins and ATP levels. Immunofluorescent staining of LC3 was co-localized mostly with a neuronal marker and microglial marker but was not co-localized with a marker for astrocytes in rats exposed to sevoflurane. These rats had poorer performance in the NOR and FC tests than control rats during young adulthood. Melatonin treatment reversed the abnormal expression of mitophagy proteins, mitochondrial energy metabolism, the activity of microglia, and impaired cognition. These ameliorations were blocked by an autophagy inhibitor, 3-MA, except for the activation of microglia. CONCLUSION: We have demonstrated that melatonin inhibits microglial activation by enhancing mitophagy and finally significantly reduces sevoflurane-induced deficits in cognition in neonatal rats. These results suggest that melatonin might be beneficial if considered when the anesthesia must be administered at a very young age.

Comprehensive Metabolite Identification of Genipin in Rats Using Ultra-High-Performance Liquid Chromatography Coupled with High Resolution Mass Spectrometry.

Genipin, an aglycone of geniposide, is a rich iridoid component in the fruit of Gardenia jasminoides Ellis and has numerous biological activities. However, its metabolic profiles in vivo and vitro remain unclear. In this study, an effective analytical strategy based on ultra-high-performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) in positive and negative ion modes was developed to analyze and identify genipin metabolites in rat urine, blood, feces, and fecal fermentation in combination with many methods including post-collection data mining methods, high-resolution extracted ion chromatography (HREIC), and multiple mass defect filtering (MMDF). Simultaneously, the metabolites of genipin in vivo were verified by fecal fermentation of SD rats at different times. Finally, based on information such as reference substances, chromatographic retention behavior, and accurate mass determination, a total of 50 metabolites (including prototypes) were identified in vivo. Among them, 7, 31 and 28 metabolites in vivo were identified in blood, urine, and feces, respectively. Our results showed that genipin could generate different metabolites that underwent multiple metabolic reactions in vivo including methylation, hydroxylation, dehydroxylation, hydrogenation, sulfonation, glucuronidation, demethylation, and their superimposed reactions. Forty-six metabolites were verified in vitro. Meanwhile, 2 and 19 metabolites identified in blood and urine were also verified in fecal fermentation at different times. These results demonstrated that metabolites were produced in feces and reabsorbed into the body. In conclusion, the newly discovered metabolites of genipin can provide a new perspective for understanding its pharmacological effects and build the foundation for thee toxicity and safety evaluations of genipin.