The alleviatory effects of koumine on MSU-induced gouty arthritis via the TLR4/NF-κB/NLRP3 pathway.

The aim of this study was to validate the preventive effects of koumine (KM), a monoterpene indole alkaloid, on gouty arthritis (GA) and to explore its possible mechanisms. C57BL/6 mice were intraperitoneally administered KM (0.8, 2.4 or 7.2 mg/kg), colchicine (3.0 mg/kg) or sterile saline. One hour later, a monosodium urate (MSU) suspension was injected into the right hind paws of the mice to establish an acute gout model. Inflammation symptoms were evaluated at 0, 3, 6, 12 and 24 h, and the mechanical withdrawal threshold was evaluated at 0, 6 and 24 h. After 24 h, the mice were euthanized, and the joint tissue, kidney and blood were collected for subsequent experiments. Histological examination and antioxidant enzyme, kidney index and serum uric acid (UA) measurements were taken. The expression levels of the signalling pathway components were determined. KM effectively alleviated the symptoms of redness, swelling and pain; counteracted inflammatory cell infiltration; and increased antioxidant enzyme levels, reduced kidney index and seru UA levels through regulating UA excretion in MSU-induced mice. The expression of toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) signalling pathway proteins and mRNA were reduced in the KM group. These results suggest that KM may be effective in alleviating GA through the TLR4/NF-κB/NLRP3 pathway.

Advances in Host-Free White Organic Light-Emitting Diodes Utilizing Thermally Activated Delayed Fluorescence: A Comprehensive Review.

The ever-growing prominence and widespread acceptance of organic light-emitting diodes (OLEDs), particularly those employing thermally activated delayed fluorescence (TADF), have firmly established them as formidable contenders in the field of lighting technology. TADF enables achieving a 100% utilization rate and efficient luminescence through reverse intersystem crossing (RISC). However, the effectiveness of TADF-OLEDs is influenced by their high current density and limited device lifetime, which result in a significant reduction in efficiency. This comprehensive review introduces the TADF mechanism and provides a detailed overview of recent advancements in the development of host-free white OLEDs (WOLEDs) utilizing TADF. This review specifically scrutinizes advancements from three distinct perspectives: TADF fluorescence, TADF phosphorescence and all-TADF materials in host-free WOLEDs. By presenting the latest research findings, this review contributes to the understanding of the current state of host-free WOLEDs, employing TADF and underscoring promising avenues for future investigations. It aims to serve as a valuable resource for newcomers seeking an entry point into the field as well as for established members of the WOLEDs community, offering them insightful perspectives on imminent advancements.

Bidirectional Solid-State Fermentation of Highland Barley by Edible Fungi to Improve Its Functional Components, Antioxidant Activity and Texture Characteristics.

In food industry, the characteristics of food substrate could be improved through its bidirectional solid-state fermentation (BSF) by fungi, because the functional components were produced during BSF. Six edible fungi were selected for BSF to study their effects on highland barley properties, such as functional components, antioxidant activity, and texture characteristics. After BSF, the triterpenes content in Ganoderma lucidum and Ganoderma leucocontextum samples increased by 76.57 and 205.98%, respectively, and the flavonoids content increased by 62.40% (Phellinus igniarius). Protein content in all tests increased significantly, with a maximal increase of 406.11% (P. igniarius). Proportion of indispensable amino acids increased significantly, with the maximum increase of 28.22%. Lysine content increased largest by 437.34% to 3.310 mg/g (Flammulina velutipes). For antioxidant activity, ABTS radical scavenging activity showed the maximal improvement, with an increase of 1268.95%. Low-field NMR results indicated a changed water status of highland barley after fermentation, which could result in changes in texture characteristics of highland barley. Texture analysis showed that the hardness and chewiness of the fermented product decreased markedly especially in Ganoderma lucidum sample with a decrease of 77.96% and 58.60%, respectively. The decrease indicated a significant improvement in the taste of highland barley. The results showed that BSF is an effective technology to increase the quality of highland barley and provide a new direction for the production of functional foods.

GSDMD/Drp1 signaling pathway mediates hippocampal synaptic damage and neural oscillation abnormalities in a mouse model of sepsis-associated encephalopathy.

BACKGROUND: Gasdermin D (GSDMD)-mediated pyroptotic cell death is implicated in the pathogenesis of cognitive deficits in sepsis-associated encephalopathy (SAE), yet the underlying mechanisms remain largely unclear. Dynamin-related protein 1 (Drp1) facilitates mitochondrial fission and ensures quality control to maintain cellular homeostasis during infection. This study aimed to investigate the potential role of the GSDMD/Drp1 signaling pathway in cognitive impairments in a mouse model of SAE. METHODS: C57BL/6 male mice were subjected to cecal ligation and puncture (CLP) to establish an animal model of SAE. In the interventional study, mice were treated with the GSDMD inhibitor necrosulfonamide (NSA) or the Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1). Surviving mice underwent behavioral tests, and hippocampal tissues were harvested for histological analysis and biochemical assays at corresponding time points. Haematoxylin-eosin staining and TUNEL assays were used to evaluate neuronal damage. Golgi staining was used to detect synaptic dendritic spine density. Additionally, transmission electron microscopy was performed to assess mitochondrial and synaptic morphology in the hippocampus. Local field potential recordings were conducted to detect network oscillations in the hippocampus. RESULTS: CLP induced the activation of GSDMD, an upregulation of Drp1, leading to associated mitochondrial impairment, neuroinflammation, as well as neuronal and synaptic damage. Consequently, these effects resulted in a reduction in neural oscillations in the hippocampus and significant learning and memory deficits in the mice. Notably, treatment with NSA or Mdivi-1 effectively prevented these GSDMD-mediated abnormalities. CONCLUSIONS: Our data indicate that the GSDMD/Drp1 signaling pathway is involved in cognitive deficits in a mouse model of SAE. Inhibiting GSDMD or Drp1 emerges as a potential therapeutic strategy to alleviate the observed synaptic damages and network oscillations abnormalities in the hippocampus of SAE mice.

The association between systemic inflammatory response index and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention.

BACKGROUND: The systemic inflammatory response index (SIRI), served as a novel inflammatory biomarker, is the synthesis of neutrophils, monocytes and lymphocytes. AIMS: We hypothesized that SIRI has predictive value for contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: We retrospectively observed 5685 patients undergoing elective PCI from January 2012 to December 2018. Venous blood samples were collected to obtain the experimental data on the day of admission or the morning of the next day. SIRI = neutrophil count × monocyte count/lymphocyte count. CA-AKI was defined as an increase of 50% or 0.3 mg/dl in SCr from baseline within 48 h after contrast exposure. RESULTS: The incidence of CA-AKI was 6.1% (n = 352). The best cutoff value of SIRI for predicting CA-AKI was 1.39, with a sensitivity of 52.3% and a specificity of 67.3%. [AUC: 0.620, 95% confidence interval (CI): 0.590-0.651, p < 0.001]. After adjusting for potential confounders, multivariate analysis showed that the high SIRI group (SIRI > 1.39) was a strong independent predictor of CA-AKI in patients undergoing elective PCI compared with the low SIRI group (SIRI ≤ 1.39) (odds ratio = 1.642, 95% CI: 1.274-2.116, p < 0.001). Additionally, COX regression analysis showed that SIRI > 1.39 was significantly associated with long-term mortality at a median follow-up of 2.8 years. [Hazard ratio (HR)=1.448, 95%CI: 1.188-1.765; p < 0.001]. Besides, Kaplan-Meier survival curve also indicated that the cumulative rate of mortality was considerably higher in the high SIRI group. CONCLUSIONS: High levels of SIRI are independent predictors of CA-AKI and long-term mortality in patients undergoing elective PCI.

Effects of atropine eyedrops at ten different concentrations for myopia control in children: A systematic review on meta-analysis.

PURPOSE: To estimate the effect of atropine eyedrops at different concentrations for myopia control in children. METHODS: We conducted a Bayesian random-effects network meta-analysis based on randomized controlled trials (RCT). Primary outcomes include changes in spherical equivalent error (SER) and changes in axial length (AL), mean difference (MD) together with 95% credible interval (CrI) were used to evaluate the efficacy. RESULTS: 28 RCTs (6608 children) were included in this review. Comparing ten atropine eyedrops (0.0025%, 0.005%, 0.01%, 0.02%, 0.025%, 0.05%, 0.1%, 0.25%, 0.5% and 1% concentrations) with the placebo, the MDs and 95%CrIs of changes in SER are -0.006 (-0.269, 0.256) D, 0.216 (-0.078, 0.508) D, 0.146 (0.094, 0.199) D, 0.167 (0.039, 0.297) D, 0.201 (0.064, 0.341) D, 0.344 (0.251, 0.440) D, 0.255 (0.114, 0.396) D, 0.296 (0.140, 0.452) D, 0.331 (0.215, 0.447) D, and 0.286 (0.195, 0.337) D, respectively. The MDs and 95%CrIs of changes in AL are -0.048 (-0.182, 0.085) mm, -0.078 (-0.222, 0.066) mm, -0.095 (-0.130, -0.060) mm, -0.096 (-0.183, -0.009) mm, -0.083 (-0.164, -0.004) mm, -0.114 (-0.176, -0.056) mm, -0.134 (-0.198, -0.032) mm, -0.174 (-0.315, -0.061) mm, -0.184 (-0.291, -0.073) mm, and -0.171 (-0.203, -0.097) mm, respectively.Whether evaluated by SER or AL, 1% concentration ranks first in efficacy, but the risk of photophobia is 17 times higher than 0.01% concentration. CONCLUSIONS: 0.01% or higher concentration atropine eyedrops are effective for myopia control, while 0.0025% and 0.005% concentrations may not. As the concentration increases, the effect tends to increase, 1% concentration may have the strongest effect.

The Association Between the Albumin-Bilirubin Score and Contrast-Associated Acute Kidney Injury in Patients Undergoing Elective Percutaneous Coronary Intervention.

The albumin-bilirubin (ALBI) score is considered an effective and convenient scoring system for assessing liver function. We hypothesized that the ALBI score was predictive of contrast-associated acute kidney injury (CA-AKI) and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI). We retrospectively observed 5629 patients undergoing elective PCI. Contrast-associated acute kidney injury is defined as a 50% or 0.3 mg/dl increase in baseline serum creatinine levels within 48 h of contrast exposure. The incidence of CA-AKI was 6.2% (n = 350). After adjusting for potential confounding factors, multivariate analysis showed that the ALBI score was an independent predictor of CA-AKI (P = .002). A restricted cubic spline analysis confirmed approximately linear relationships between the ALBI score and risks of CA-AKI. Furthermore, at a median follow-up of 2.8 years, multivariate Cox regression analysis indicated that the ALBI score was an independent risk factor for long-term mortality (P < .001). The ALBI score was closely related to the occurrence of CA-AKI and long-term mortality in patients who underwent elective PCI. This score might be useful for risk stratification in high-risk patient groups to predict CA-AKI.

An auxiliary diagnostic tool for common fundus diseases based on fundus color photography and light-weight classification models.

OBJECTIVE: To evaluate the performance of two lightweight neural network models in the diagnosis of common fundus diseases and make comparison to another two classical models. METHODS: A total of 16,000 color fundus photography were collected, including 2000 each of glaucoma, diabetic retinopathy (DR), high myopia, central retinal vein occlusion (CRVO), age-related macular degeneration (AMD), optic neuropathy, and central serous chorioretinopathy (CSC), in addition to 2000 normal fundus. Fundus photography was obtained from patients or physical examiners who visited the Ophthalmology Department of Beijing Tongren Hospital, Capital Medical University. Each fundus photography has been diagnosed and labeled by two professional ophthalmologists. Two classical classification models (ResNet152 and DenseNet121), and two lightweight classification models (MobileNetV3 and ShufflenetV2), were trained. Area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were used to evaluate the performance of the four models. RESULTS: Compared with the classical classification model, the total size and number of parameters of the two lightweight classification models were significantly reduced, and the classification speed was sharply improved. Compared with the DenseNet121 model, the ShufflenetV2 model took 50.7% less time to make a diagnosis on a fundus photography. The classical models performed better than lightweight classification models, and Densenet121 showed highest AUC in five out of the seven common fundus diseases. However, the performance of lightweight classification models is satisfying. The AUCs using MobileNetV3 model to diagnose AMD, diabetic retinopathy, glaucoma, CRVO, high myopia, optic atrophy, and CSC were 0.805, 0.892, 0.866, 0.812, 0.887, 0.868, and 0.803, respectively. For ShufflenetV2model, the AUCs for the above seven diseases were 0.856, 0.893, 0.855, 0.884, 0.891, 0.867, and 0.844, respectively. CONCLUSION: The training of light-weight neural network models based on color fundus photography for the diagnosis of common fundus diseases is not only fast but also has a significant reduction in storage size and parameter number compared with the classical classification model, and can achieve satisfactory accuracy.

Predictive Value of Systemic Inflammation Score for Contrast-Associated Acute Kidney Injury and Adverse Outcomes Among Patients Undergoing Elective Percutaneous Coronary Intervention.

Purpose: Prior research has demonstrated a key role of systemic inflammatory state in the pathogenesis and progression of contrast-associated acute kidney injury (CA-AKI). Recently, the systemic inflammation score (SIS) has been introduced to evaluate the inflammatory status, utilizing the lymphocyte-to-monocyte ratio (LMR) and albumin. The primary objective of this study was to determine whether the SIS can predict CA-AKI and long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI). Patients and Methods: A total of 5726 patients who underwent elective PCI were included from January 2012 to December 2018. The primary outcome was CA-AKI, defined as an increase in serum creatinine (SCr) ≥0.3 mg/dl or ≥50% than baseline SCr within 48 h after the PCI procedure. The secondary outcome was long-term mortality. All patients were classified into low- and high-SIS groups. Results: During hospitalization, 349 (6.1%) patients developed CA-AKI. Multivariate logistic regression analysis showed that patients in the high SIS group had a 1.47-fold higher risk of developing CA-AKI than those in the low SIS group [odds ratio (OR): 1.50, 95% confidence interval (CI): 1.12-2.01, P =0.006]. Furthermore, the SIS showed the greatest prediction performance for CA-AKI compared with other inflammatory hematological ratios. In the multivariate Cox regression analysis, the high SIS group was found to be closely associated with long-term mortality [hazard ratio (HR): 1.58, 95% CI: 1.26-1.97, P <0.001, vs low SIS group]. The Kaplan-Meier curve analysis also demonstrated a difference in long-term mortality between the two groups (Log rank test, P <0.001). Conclusion: The SIS was closely associated with CA-AKI and long-term mortality in patients after elective PCI. Thus, more attention should be paid to exploring the potential benefits of anti-inflammatory strategies in preventing CA-AKI and improving the prognosis of patients undergoing PCI.

Normal thyroid stimulating hormone is associated with all-cause mortality in patients with acute myocardial infarction after percutaneous coronary intervention.

BACKGROUND: Circulating thyroid-stimulating hormone (TSH) levels within the normal reference range can affect the cardiovascular system. The present study investigated the prognostic value of normal TSH levels in patients presenting with acute myocardial infarction (AMI) following percutaneous coronary intervention (PCI). METHODS: Between January 2013 and July 2019, 1240 patients with AMI and normal thyroid function were enrolled and classified according to TSH tertile. The trial endpoint was all-cause mortality. The integrated discrimination index (IDI) and the net reclassification index (NRI) were used to assess the combined predictive values of the TSH levels and the Global Registry of Acute Coronary Events (GRACE) scores. RESULTS: After a median 44.25-month follow-up, 195 individuals died. Even after covariate adjustment by multivariate Cox regression (HR: 1.56; 95% CI 1.08-2.25; P = 0.017), the patients in the third TSH tertile were at the highest risk of all-cause mortality. A subgroup analysis revealed significant interactions between the TSH levels and the GRACE scores (high risk vs. low/medium risk) (P = 0.019). The addition of the TSH levels to the GRACE scores substantially improved the prediction of all-cause mortality, especially for high-risk patients (NRI = 0.239; IDI = 0.044; C-statistic value range 0.649-0.691; all significant). CONCLUSIONS: The third TSH tertile is associated with a higher incidence of all-cause mortality than the first TSH tertile in high-risk patients presenting with AMI after PCI.

Compact conformal tattoo-polymer antenna for on-body wireless power transfer.

This paper presents a 35.0 × 35.0 × 2.7 mm3 compact, low-profile, and lightweight wearable antenna for on-body wireless power transfer. The proposed antenna can be easily printed on a piece of flexible tattoo paper and transformed onto a PDMS substrate, making the entire antenna structure conform to the human body for achieving a better user experience. Here, a layer of frequency selective surface (FSS) is inserted in between the antenna and human tissue, which has successfully reduced the loading effects of the tissue, with 13.8 dB improvement on the antenna gain. Also, the operating frequency of the rectenna is not affected much by deformation. To maximize the RF-DC conversion efficiency, a matching loop, a matching stub, and two coupled lines are integrated with the antenna for tuning the rectenna so that a wide bandwidth (~ 24%) can be achieved without the use of any external matching networks. Measurement results show that the proposed rectenna can achieve a maximum conversion efficiency of 59.0% with an input power of 5.75 µW/cm2 and can even exceed 40% for a low input power of 1.0 µW/cm2 with a 20 kΩ resistive load, while many other reported rectennas can only achieve a high PCE at a high power density level, which is not always practical for a wearable antenna.

Six-month repeated irradiation of 650 nm low-level red light reduces the risk of myopia in children: a randomized controlled trial.

PURPOSE: To evaluate whether the six-month repeated irradiation of 650 nm low-level red light (LLRL) decreases the risk of myopia onset in children. METHODS: This was a single-masked, randomized controlled trial. A total of 112 children (aged 6-12 years) were enrolled and randomized to the treatment group or control group in a 1:1 ratio. The cycloplegic spherical equivalent error (SER) of children at baseline was -0.5 diopter (D) to 3D. Children in the treatment group were irradiated with the 650 nm LLRL for 6 min daily. No intervention was given to the control. The primary outcomes are myopia incidence, change in cycloplegic SER, and change in axial length (AL). RESULTS: For the treatment group and control group, the six-month myopia incidence rates were 1.8% (95% confidence interval, CI: 0.2-4.9%) and 12.5% (95% CI: 5.5-21.9%), respectively. The difference was significant (p = 0.028). The median changes in AL for the treatment group and control group were -0.02 (interquartile range, IQR: -0.12 to 0.06) mm, and 0.09 (IQR: 0-0.18) mm, respectively. The difference was significant (p < 0.001). The median changes in cycloplegic SER for the treatment group and control group were 0 (IQR: 0-0.25) D, and -0.125 (IQR: -0.375 to 0) D, respectively. The difference was significant (p < 0.001). There was no adverse event. CONCLUSION: The repeated irradiation of 650 nm LLRL may have a strong effect for myopia prevention in children, without risk of adverse events. TRIAL REGISTRATION: this trial is retrospectively registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ), the registration number is ChiCTR2200058963.

D-Optimal Design and Development of a Koumine-Loaded Microemulsion for Rheumatoid Arthritis Treatment: In vivo and in vitro Evaluation.

Introduction: Koumine (KME) is the most abundant active ingredient separated from Gelsemium elegans Benth and exhibits a significant therapeutic effect on rheumatoid arthritis (RA). It is a lipophilic compound with poor aqueous solubility, and there is an urgent need to develop novel dosage forms of KME and promote its clinical application for the treatment of RA. The aim of this study was to design and develop KME-loaded microemulsions (KME-MEs) for the effective management of RA. Methods: The composition of the microemulsion was selected by carrying out a solubility study and generating pseudoternary phase diagrams, and further optimized by D-Optimal design. The optimized KME-MEs was evaluated for particle size, viscosity, drug release, storage stability, cytotoxicity, cellular uptake, Caco-2 cell transport and everted gut sac investigations. In vivo fluorescence imaging and the therapeutic effects of KME and KME-MEs on collagen-induced arthritis (CIA) rats were also evaluated. Results: The optimized microemulsion contained 8% oil, 32% Smix (surfactant/cosurfactant) and 60% water and was used for in vivo and in vitro studies. The optimal KME-MEs exhibited a small globule size of 18.5 ± 0.14 nm and good stability over 3 months, and the release kinetics followed a first-order model. These KME-MEs had no toxic effect on Caco-2 cells but were efficiently internalized into the cytoplasm. Compared to KME, the KME-MEs displayed significantly increased permeability and absorption in Caco-2 cell monolayer assay and ex vivo everted gut sac experiment. As expected, the KME-MEs attenuated the progression of RA in CIA rats and were more effective than free KME with a reduced frequency of administration. Conclusion: The KME-MEs improved the solubility and therapeutic efficacy of KME by employing formulation technology. These results provide a promising vehicle for the oral delivery of KME to treat RA and have attractive potential for clinical translation.

Ligamentum teres hepatis as a graft for portal and/or superior mesenteric vein reconstruction: From bench to bedside.

BACKGROUND: Pancreaticoduodenectomy combined with portal vein (PV) and/or superior mesenteric vein (SMV) resection in patients with pancreaticobiliary malignancy has become a common surgical procedure. There are various grafts currently used for PV and/or SMV reconstruction, but each of these grafts have certain limitations. Therefore, it is necessary to explore novel grafts that have an extensive resource pool, are low cost with good clinical application, and are without immune response rejection or additional damage to patients. AIM: To observe the anatomical and histological characteristics of the ligamentum teres hepatis (LTH) and evaluate PV/SMV reconstruction using an autologous LTH graft in pancreaticobiliary malignancy patients. METHODS: In 107 patients, the post-dilated length and diameter in resected LTH specimens were measured. The general structure of the LTH specimens was observed by hematoxylin and eosin (HE) staining. Collagen fibers (CFs), elastic fibers (EFs), and smooth muscle (SM) were visualized by Verhoeff-Van Gieson staining, and the expression of CD34, factor VIII-related antigen (FVIIIAg), endothelial nitric oxide synthase (eNOS), and tissue type plasminogen activator (t-PA) were detected using immunohistochemistry in LTH and PV (control) endothelial cells. PV and/or SMV reconstruction using the autologous LTH was conducted in 26 patients with pancreaticobiliary malignancies, and the outcomes were retrospectively analyzed. RESULTS: The post-dilated length of LTH was 9.67 ± 1.43 cm, and the diameter at a pressure of 30 cm H2O was 12.82 ± 1.32 mm at the cranial end and 7.06 ± 1.88 mm at the caudal end. Residual cavities with smooth tunica intima covered by endothelial cells were found in HE-stained LTH specimens. The relative amounts of EFs, CFs and SM in the LTH were similar to those in the PV [EF (%): 11.23 ± 3.40 vs 11.57 ± 2.80, P = 0.62; CF (%): 33.51 ± 7.71 vs 32.11 ± 4.82, P = 0.33; SM (%): 15.61 ± 5.26 vs 16.74 ± 4.83, P = 0.32]. CD34, FVIIIAg, eNOS, and t-PA were expressed in both LTH and PV endothelial cells. The PV and/or SMV reconstructions were successfully completed in all patients. The overall morbidity and mortality rates were 38.46% and 7.69%, respectively. There were no graft-related complications. The postoperative vein stenosis rates at 2 wk, 1 mo, 3 mo and 1 year were 7.69%, 11.54%, 15.38% and 19.23%, respectively. In all 5 patients affected, the degree of vascular stenosis was less than half of the reconstructed vein lumen diameter (mild stenosis), and the vessels remained patent. CONCLUSION: The anatomical and histological characteristics of LTH were similar to the PV and SMV. As such, the LTH can be used as an autologous graft for PV and/or SMV reconstruction in pancreaticobiliary malignancy patients who require PV and/or SMV resection.

Ar plasma assists in enhanced oxygen evolution kinetics of MOG-derived multicomponent transition metal sulfides.

Transition metal sulfides are low-cost oxygen evolution reaction (OER) electrocatalysts that can potentially substitute noble metal catalysts. However, the adsorption process of their OER is impeded by their intrinsic poor catalytic activity. Constructing heterojunction and vacancy defects in transition metal sulfides is an efficient method to promote the process of oxygen evolution. Herein, a facile approach based on in situ sulfurization of metal-organic gels (MOGs) and a short-time plasma treatment was developed to fabricate vacancy-modified polymetallic sulfides heterojunction. The synergistic effect of the multi-component heterojunction and sulfur vacancy contributed greatly to improving the electron migration efficiency and OER ability of the electrocatalyst. As a result, the optimum oxygen evolution activity was achieved with appropriate surface vacancy concentrations by regulating the plasma radio frequency powers. The plasma-treated catalyst under 400 W showed the best OER performance (lower overpotential of 235 mV in 1 M KOH solution with the Tafel slope of 31 mV dec-1) and good durability over 11 h of chronopotentiometry testing. This work sheds new light on constructing multimetal-based heterojunction electrocatalysts with rich vacancy defects for oxygen evolution reactions.

Koumine alleviates rheumatoid arthritis by regulating macrophage polarization.

ETHNOPHARMACOLOGICAL RELEVANCE: The imbalance between M1-and M2-polarized macrophages is one of the major pathophysiological changes in RA. Therefore, targeted macrophage polarization may be an effective therapy for RA. Koumine, an alkaloid monomer with the highest content and low toxicity in Gelsemium elegans Benth., has the effect of treating RA by playing an immunomodulatory role by influencing various immune cells. However, whether koumine affects macrophage polarization in RA and the associated molecular mechanisms remain unknown. AIM OF THE STUDY: To investigate the mechanism of the anti-RA effect of koumine on macrophage polarization. MATERIALS AND METHODS: The effect of koumine on macrophage polarization was investigated in vivo and in vitro. We first explored the effects of koumine on AIA rats and detected the levels of M1/M2 macrophage polarization markers in the spleen by western blotting. Then, we explored the regulatory effect of koumine on M1/M2 macrophage polarization and the effect on the PI3K/AKT signaling pathway in vitro. Finally, we verified the effects of koumine on macrophage polarization in CIA mice. RESULTS: We found that koumine alleviated symptoms, including relieving pain, reducing joint redness and swelling in AIA rats and restoring the M1/M2 macrophage balance in vivo. Interestingly, koumine had an inhibitory effect on both M1 and M2 macrophage polarization in vitro, but it had a stronger inhibitory effect on M1 macrophage. In a mixed polarization experiment, koumine mainly inhibited M1 macrophage polarization and had an inhibitory effect on the PI3K/AKT signaling pathway. Finally, we found that koumine had therapeutic effects on CIA mice, regulated macrophage polarization and inhibited the PI3K/AKT signaling pathway. CONCLUSIONS: Our results reveal that koumine regulates macrophage polarization through the PI3K/AKT signaling pathway. This may be one of the important mechanisms of its anti-RA effect, which provides a theoretical and scientific basis for the possible clinical application of koumine.

[Research progress of ferroptosis in hypoxia-associated brain injury].

Cerebral hypoxia often brings irreversible damage to the central nervous system, which seriously endangers human health. It is of great significance to further explore the mechanism of hypoxia-associated brain injury. As a programmed cell death, ferroptosis mainly manifests as cell death caused by excessive accumulation of iron-dependent lipid peroxides. It is associated with abnormal glutathione metabolism, lipid peroxidation and iron metabolism, and is involved in the occurrence and development of various diseases. Studies have found that ferroptosis plays an important role in hypoxia-associated brain injury. This review summarizes the mechanism of ferroptosis, and describes its research progress in cerebral ischemia reperfusion injury, neonatal hypoxic-ischemic brain damage, obstructive sleep apnea-induced brain injury and high-altitude hypoxic brain injury.

Association between dosing of spironolactone and outcomes in heart failure with preserved ejection fraction patients combined with chronic kidney disease------Balance of efficacy and risk.

Aims: Few studies have compared the association between dosing of spironolactone and outcomes in patients with heart failure with preserved ejection fraction (HFpEF), and whether spironolactone dose could significantly affect the prognosis of HFpEF patients combined with chronic kidney disease (CKD) remains unclear. Our aim was to directly compare 'high vs. low' doses of spironolactone in an attempt to find a benefit-risk-balanced point, and infer an adequate dose for HFpEF with CKD patients. Methods: Overall, 4,321 symptomatic heart failure inpatients were initially screened from January 2013 to December 2019, and all enrolled patients were followed-up for 36 months; After including patients who meet the diagnostic criteria of HFpEF and CKD with ejection fraction > 45% and estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2, a total of 387 patients was selected. Primary outcome was a composite of all-cause death, heart failure (HF) hospitalization and non-fatal stroke. The key safety outcome was hyperkalemia rates during the follow-up period. Results: The primary outcome event rates in patients with or without spironolactone were 12.74 and 21.45 per 100 person-years, respectively. Compared with patients not taking spironolactone, the adjusted hazard ratio (HR) [95% confidence interval (CI)] was 0.55 (0.38-0.79) with spironolactone group for primary outcomes. After grouped by the daily dose of spironolactone, low-dose group (≤ 40 mg) was associated with lower relative risk for the primary efficacy outcome [adjusted HR (95% CI) was 0.43 (0.23-0.81), 0.50 (0.33-0.76) and 0.74 (0.36-2.79) with < 40 mg, 40 mg and >40 mg, respectively]. During 3-year follow-up, the risk for hyperkalemia was amplified in the higher dose group (>40 mg) while showed no significant difference compared with low dose group (p = 0.425). Conclusion: HFpEF with CKD patients using spironolactone had lower risk of adverse cardiovascular outcomes. And the use of low-dose spironolactone (≤ 40 mg) showed the best efficacy and safety, therefore we may recommend ≤ 40 mg as the optimal initial dose for these patients. However, this was a relatively small sample size, retrospective study, and further adequately powered randomized trials are needed to verify these results.

Basolateral amygdala astrocytes modulate diabetic neuropathic pain and may be a potential therapeutic target for koumine.

BACKGROUND AND PURPOSE: New remedies are required for the treatment of diabetic neuropathic pain (DNP) due to insufficient efficacy of available therapies. Here, we used chemogenetic approaches combined with in vivo pharmacology to elucidate the role of basolateral amygdala (BLA) astrocytes in DNP pathogenesis and provide new insights into therapeutic strategies for DNP. EXPERIMENTAL APPROACH: A streptozotocin-induced DNP model was established. Designer receptors exclusively activated by designer drugs (DREADDs) were used to regulate astrocyte activity. Mechanical hyperalgesia was assessed using the electronic von Frey test. Anxiety-like behaviours were detected using open field and elevated plus maze tests. Astrocytic activity was detected by immunofluorescence, and cytokine content was determined by ELISA. KEY RESULTS: BLA astrocytes were regulated by DREADDs, and inhibition of BLA astrocytes attenuated mechanical allodynia and pain-related negative emotions in DNP rats. In contrast, temporary activation of BLA astrocytes induced allodynia without anxious behaviours in naive rats. In addition, koumine (KM) alleviated mechanical allodynia and anxiety-like behaviours in DNP rats, inhibited the activation of BLA astrocytes and suppressed the inflammatory response. Furthermore, persistent activation of BLA astrocytes through chemogenetics mimicked chronic pain, and KM alleviated the pain hypersensitivity and anxiety-like behaviours. CONCLUSION AND IMPLICATIONS: DREADDs bidirectionally regulate the activity of BLA astrocytes, which proves for the first time the role of BLA astrocyte activation in the pathogenesis of DNP and represents a novel therapeutic strategy for DNP. KM ameliorates DNP, perhaps by inhibiting the activation of BLA astrocytes and reveal KM as a potential candidate for treating DNP.