Studies on the Anti-Inflammatory Effect of Xiaoyao Pills in The Treatment of Postmenopausal Osteoporosis in Mice.

Osteoporosis is a common metabolic disease of elderly and postmenopausal women, with no obvious symptoms during its early stages. In the latter stages of this condition, the patients are prone to fractures, and this can seriously affect their health and quality of life. The worldwide increase in life expectancy has made osteoporosis a global concern. The Xiaoyao pills were previously used in the treatment of depression. In addition, the drug appeared to have estrogen-like activity, which affected the expression of ALP, an early osteoblast-specific marker, and COL-1, a major component of bone extracellular matrix. Xiaoyao pills were assessed for their effects on postmenopausal osteoporosis (PMOM) in mice. The target information of each herbal component of Xiaoyao pills was accessed through the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Information from GeneCards, OMIM, PharmGkb, TTD, DrugBank, and other websites was used to construct the regulatory network of the herbal complex through Cytoscape and String network to assess the protein interactions. Mice were ovariectomized, and treated with high and low doses of Xiaoyao pills and these were compared to controls. Their symptoms were assessed by immunocytochemistry of bone tissues. The results suggested that Xiaoyao pills had the ability to alleviate the symptoms of PMOM in ovariectomized mice through the IL-17 signaling pathway. This drug has the potential to become a novel therapeutic agent for the treatment of osteoporosis.

Intrinsic Activity Identification of Noble Metal Single-Sites for Electrocatalytic Chlorine Evolution.

Single-atom catalysts with maximal atom-utilization have emerged as promising alternatives for chlorine evolution reaction (CER) toward valuable Cl2 production. However, understanding their intrinsic CER activity have so far been plagued due to the lack of well-defined atomic structure controlling. Herein, we prepare and identify a series of atomically dispersed noble metals (e.g., Pt, Ir, Ru) in nitrogen-doped nanocarbons (M1-N-C) with an identical M-N4 moiety, which allows objective activity evaluation. Electrochemical experiments, operando Raman spectroscopy, and quasi-in situ electron paramagnetic resonance spectroscopy analyses collectively reveal that all the three M1-N-C proceed the CER via a direct Cl-mediated Vomer-Heyrovský mechanism with reactivity following the trend of Pt1-N-C > Ir1-N-C > Ru1-N-C. Density functional theory (DFT) calculations reveal that this activity trend is governed by the binding strength of Cl*-Cl intermediate (ΔGCl*-Cl) on M-N4 sites (Pt < Ir < Ru) featuring distinct d-band centers, providing a reliable thermodynamic descriptor for rational design of single metal sites toward Cl2 electrosynthesis.

Impact of a Potent Strain of Plant Growth-Promoting Bacteria (PGPB), Bacillus subtilis S1 on Bacterial Community Composition, Enzymatic Activity, and Nitrogen Content in Cucumber Rhizosphere Soils.

Antagonistic bacterial strains from Bacillus spp. have been widely studied and utilized in the biocontrol of phytopathogens and the promotion of plant growth, but their impacts on the rhizosphere microecology when applied to crop plants are unclear. Herein, the effects of applying the antagonistic bacterium Bacillus subtilis S1 as a biofertilizer on the rhizosphere microecology of cucumbers were investigated. In a pot experiment on cucumber seedlings inoculated with S1, 3124 bacterial operational taxonomic units (OTUs) were obtained from the rhizosphere soils using high-throughput sequencing of 16S rRNA gene amplicons, and the most abundant phylum was Proteobacteria that accounted for 49.48% in the bacterial community. S1 treatment significantly reduced the abundances of soil bacterial taxa during a period of approximately 30 days but did not affect bacterial diversity in the rhizosphere soils of cucumbers. The enzymatic activities of soil nitrite reductase (S-Nir) and dehydrogenase (S-DHA) were significantly increased after S1 fertilization. However, the activities of soil urease (S-UE), cellulase (S-CL), and sucrase (S-SC) were significantly reduced compared to the control group. Additionally, the ammonium- and nitrate-nitrogen contents of S1-treated soil samples were significantly lower than those of the control group. S1 fertilization reshaped the rhizosphere soil bacterial community of cucumber plants. The S-CL activity and nitrate-nitrogen content in rhizosphere soil affected by S1 inoculation play important roles in altering the abundance of rhizosphere soil microbiota.

Source-independent quantum secret sharing with entangled photon pair networks.

The large-scale deployment of quantum secret sharing (QSS) in quantum networks is currently challenging due to the requirements for the generation and distribution of multipartite entanglement states. Here we present an efficient source-independent QSS protocol utilizing entangled photon pairs in quantum networks. Through the post-matching method, which means the measurement events in the same basis are matched, the key rate is almost independent of the number of participants. In addition, the unconditional security of our QSS against internal and external eavesdroppers can be proved by introducing an equivalent virtual protocol. Our protocol has great performance and technical advantages in future quantum networks.

Novel de novo SPAST mutation in a Han Chinese SPG4 patient: a case report.

Spastic paraplegia type 4 (SPG4), the predominant form of Autosomal Dominant Hereditary spastic paraplegia (AD-HSP), is characterized by variants in the SPAST gene. This study reports a unique case of a late-onset SPG4 in a Han Chinese male, manifesting primarily as gait disturbances from lower extremity spasticity. Uncovered through whole-genome sequencing, a previously undocumented frameshift variant, c.1545dupA in exon 14 of the SPAST gene, was identified. Notably, this variant was absent in asymptomatic parents with confirmed paternity and maternity status, suggesting a de novo variant occurrence. This discovery emphasizes the potential of de novo variants to exhibit a late-onset pure pattern, extending the SPG4 variant spectrum, and consideration of such variants should be given in HSP patients with a negative family history.

Ginsenoside Rg2 Attenuates Aging-Induced Liver Injury via Inhibiting Caspase 8-Mediated Pyroptosis, Apoptosis and Modulating Gut Microbiota.

Aging is an irresistible natural law of the progressive decline of body molecules, organs, and overall function with the passage of time, resulting in eventual death. World Health Organization data show that aging is correlated with a wide range of common chronic diseases in the elderly, and is an essential driver of many diseases. Panax Ginseng C.A Meyer is an ancient herbal medicine, which has an effect of "long service, light weight, and longevity" recorded in the ancient Chinese medicine book "Compendium of Materia Medica." Ginsenoside Rg2, the main active ingredient of ginseng, also exerts a marked effect on the treatment of liver injury. However, it remains unclear whether Rg2 has the potential to ameliorate aging-induced liver injury. Hence, exploring the hepatoprotective properties of Rg2 and its possible molecular mechanism by Senescence Accelerate Mouse Prone 8 (SAMP8) and gut microbiota. Our study demonstrated that Rg2 can inhibit pyroptosis and apoptosis through caspase 8, and regulate the gut-liver axis to alleviate liver inflammation by changing the composition of gut microbiota, thus improving aging-induced liver injury. These findings provide theoretical support for the pharmacological effects of ginsenosides in delaying aging-induced liver injury.

Non-Coding RNA in Schwann Cell and Peripheral Nerve Injury: A Review.

Peripheral nerve injury (PNI) can result in severe disabilities, profoundly impacting patients' quality of life and potentially endangering their lives. Therefore, understanding the potential molecular mechanisms that facilitate the regeneration of damaged nerves is crucial. Evidence indicates that Schwann cells (SCs) play a pivotal role in repairing peripheral nerve injuries. Previous studies have shown that RNA, particularly non-coding RNA (ncRNA), plays a crucial role in nerve regeneration, including the proliferation and dedifferentiation of SCs. In this review, the individual roles of ncRNA in SCs and PNI are analyzed. This review not only enhances the understanding of ncRNA's role in nerve injury repair but also provides a significant theoretical foundation and inspiration for the development of new therapeutic strategies.

Circular RNA IGF1R Promotes Cardiac Repair via Activating ß-Catenin Signaling by Interacting with DDX5 in Mice after Ischemic Insults.

The potential of circular RNAs (circRNAs) as biomarkers and therapeutic targets is becoming increasingly evident, yet their roles in cardiac regeneration and myocardial renewal remain largely unexplored. Here, we investigated the function of circIGF1R and related mechanisms in cardiac regeneration. Through analysis of circRNA sequencing data from neonatal and adult cardiomyocytes, circRNAs associated with regeneration were identified. Our data showed that circIGF1R expression was high in neonatal hearts, decreased with postnatal maturation, and up-regulated after cardiac injury. The elevation was validated in patients diagnosed with acute myocardial infarction (MI) within 1 week. In human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and myocardial tissue from mice after apical resection and MI, we observed that circIGF1R overexpression enhanced cardiomyocyte proliferation, reduced apoptosis, and mitigated cardiac dysfunction and fibrosis, while circIGF1R knockdown impeded endogenous cardiac renewal. Mechanistically, we identified circIGF1R binding proteins through circRNA precipitation followed by mass spectrometry. RNA pull-down Western blot and RNA immunoprecipitation demonstrated that circIGF1R directly interacted with DDX5 and augmented its protein level by suppressing ubiquitin-dependent degradation. This subsequently triggered the ß-catenin signaling pathway, leading to the transcriptional activation of cyclin D1 and c-Myc. The roles of circIGF1R and DDX5 in cardiac regeneration were further substantiated through site-directed mutagenesis and rescue experiments. In conclusion, our study highlights the pivotal role of circIGF1R in facilitating heart regeneration and repair after ischemic insults. The circIGF1R/DDX5/ß-catenin axis emerges as a novel therapeutic target for enhancing myocardial repair after MI, offering promising avenues for the development of regenerative therapies.

Ventral posteromedial nucleus of the thalamus gates the spread of trigeminal neuropathic pain.

BACKGROUND: Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking. METHODS: Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain. RESULTS: We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain. CONCLUSION: These results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.

Biological characteristics of flowers and examination of pollen viability at different developmental stages of Epimedium sagittatum (Sieb. et Zucc.) Maxim.

To gain a deeper understanding of the flowering pattern and reproductive characteristics of Epimedium sagittatum, to enrich the research on the flower development of E. sagittatum and its reproductive regulation, and to screen the methods suitable for the rapid detection of pollen viability of E. sagittatum and to promote its cross-breeding. The characteristics of its flower parts were observed, recorded and measured, and the pollen viability of E. sagittatumwas determined by five methods, including TTC staining, I2-KI staining, red ink staining, peroxidase method and in vitro germination method. The flowering process of E. sagittatum can be divided into five stages: calyx dehiscence, bract spathe, petal outgrowth, pollen dispersal, and pollination and withering. The results of I2-KI staining and peroxidase method were significantly higher than those of other methods; the in vitro germination method was intuitive and accurate, but the operation was complicated and time-consuming; the red ink staining method was easy to operate and had obvious staining effect, and the results were the closest to those of the in vitro germination method; and it was found that the pollen of E. sagittatum was not as effective as the in vitro germination method at the bud stamen stage, the flower stigma and the flower bud. It was also found that the pollen viability and germination rate of E. sagittatum pollen were higher in the three periods of bud spitting, petal adductor and pollen dispersal. Comparing the five methods, the red ink staining method was found to be a better method for the rapid detection of pollen viability; the best pollination periods of E. sagittatum were the bud stamen stage, petal adductor stage, and pollen dispersal stage of flowers at the peak of bloom. This study on the flowering and fruiting pattern of E. sagittatum, and the related mechanism of sexual reproduction, can be used as a reference for the next step of research on the breeding of E. sagittatum.

Anisotropy component of DTI reveals long-term neuroinflammation following repetitive mild traumatic brain injury in rats.

BACKGROUND: This study aimed to investigate the long-term effects of repetitive mild traumatic brain injury (rmTBI) with varying inter-injury intervals by measuring diffusion tensor metrics, including mean diffusivity (MD), fractional anisotropy (FA), and diffusion magnitude (L) and pure anisotropy (q). METHODS: Eighteen rats were randomly divided into three groups: short-interval rmTBI (n = 6), long-interval rmTBI (n = 6), and sham controls (n = 6). MD, FA, L, and q values were analyzed from longitudinal diffusion tensor imaging at days 50 and 90 after rmTBI. Immunohistochemical staining against neurons, astrocytes, microglia, and myelin was performed. Analysis of variance, Pearson correlation coefficient, and simple linear regression model were used. RESULTS: At day 50 post-rmTBI, lower cortical FA and q values were shown in the short-interval group (p ≤ 0.038). In contrast, higher FA and q values were shown for the long-interval group (p ≤ 0.039) in the corpus callosum. In the ipsilesional external capsule and internal capsule, no significant changes were found in FA, while lower L and q values were shown in the short-interval group (p ≤ 0.028) at day 90. The q values in the external capsule and internal capsule were negatively correlated with the number of microglial cells and the total number of astroglial cells (p ≤ 0.035). CONCLUSION: Tensor scalar measurements, such as L and q values, are sensitive to exacerbated chronic injury induced by rmTBI with shorter inter-injury intervals and reflect long-term astrogliosis induced by the cumulative injury. RELEVANCE STATEMENT: Tensor scalar measurements, including L and q values, are potential DTI metrics for detecting long-term and subtle injury following rmTBI; in particular, q values may be used for quantifying remote white matter (WM) changes following rmTBI. KEY POINTS: The alteration of L and q values was demonstrated after chronic repetitive mild traumatic brain injury. Changing q values were observed in the impact site and remote WM. The lower q values in the remote WM were associated with astrogliosis.

Association of Blood Metals and Metal Mixtures with the Myocardial Enzyme Profile: An Occupational Population-Based Study in China.

To investigate a cross-sectional association between blood metal mixture and myocardial enzyme profile, we quantified creatine kinase (CK), creatine kinase-MB (CK-MB), lactate dehydrogenase (LD), α-hydroxybutyrate dehydrogenase (α-HBD), and aspartate transaminase (AST) levels among participants from the manganese-exposed workers healthy cohort (MEWHC) (n = 544). The levels of 22 metals in blood cells were determined using inductively coupled plasma mass spectrometry. The least absolute shrinkage and selection operator (LASSO) penalized regression model was utilized for screening metals. The exposure-response relationship between specific metal and myocardial enzyme profile was identified by general linear regression and restricted cubic spline analyses. The overall effect and interactions were evaluated using Bayesian kernel machine regression (BKMR). Manganese was linearly and positively associated with CK (Poverall = 0.019, Pnon-linearity = 0.307), dominating the positive overall effect of mixture exposure (manganese, arsenic, and rubidium) on CK level. Calcium and zinc were linearly and negatively associated with LD levels (Poverall < 0.05, Pnon-linearity > 0.05), and asserted dominance in the negative overall effect of metal mixtures (rubidium, molybdenum, zinc, nickel, cobalt, calcium, and magnesium) on LD level. Interestingly, we observed a U-shaped dose-response relationship of molybdenum with LD level (Poverall < 0.001, Pnon-linearity = 0.015), an interaction between age and calcium on LD level (Pinteration = 0.041), and an interaction between smoking and molybdenum on LD level (Pinteration = 0.035). Our study provides evidence that metal mixture exposure affects the myocardial enzyme profile. Additional investigation is required to confirm these associations, and to reveal the fundamental mechanisms involved.

PEX3 promotes regenerative repair after myocardial injury in mice through facilitating plasma membrane localization of ITGB3.

The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3ß signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.

Highly Selective Electrocatalytic CO2 Conversion to Tailored Products through Precise Regulation of Hydrogenation and C-C Coupling.

The electrochemical reduction reaction of carbon dioxide (CO2RR) into valuable products offers notable economic benefits and contributes to environmental sustainability. However, precisely controlling the reaction pathways and selectively converting key intermediates pose considerable challenges. In this study, our theoretical calculations reveal that the active sites with different states of copper atoms (1-3-5-7-9) play a pivotal role in the adsorption behavior of the *CHO critical intermediate. This behavior dictates the subsequent hydrogenation and coupling steps, ultimately influencing the formation of the desired products. Consequently, we designed two model electrocatalysts comprising Cu single atoms and particles supported on CeO2. This design enables controlled *CHO intermediate transformation through either hydrogenation with *H or coupling with *CO, leading to a highly selective CO2RR. Notably, our selective control strategy tunes the Faradaic efficiency from 61.1% for ethylene (C2H4) to 61.2% for methane (CH4). Additionally, the catalyst demonstrated a high current density and remarkable stability, exceeding 500 h of operation. This work not only provides efficient catalysts for selective CO2RR but also offers valuable insights into tailoring surface chemistry and designing catalysts for precise control over catalytic processes to achieve targeted product generation in CO2RR technology.

Hydrogen Peroxide Spillover on Platinum-Iron Hybrid Electrocatalyst for Stable Oxygen Reduction.

Iron-nitrogen-carbon (Fe-N-C) catalysts, although the most active platinum-free option for the cathodic oxygen reduction reaction (ORR), suffer from poor durability due to the Fe leaching and consequent Fenton effect, limiting their practical application in low-temperature fuel cells. This work demonstrates an integrated catalyst of a platinum-iron (PtFe) alloy planted in an Fe-N-C matrix (PtFe/Fe-N-C) to address this challenge. This novel catalyst exhibits both high-efficiency activity and stability, as evidenced by its impressive half-wave potential (E1/2) of 0.93 V versus reversible hydrogen electrode (vs RHE) and minimal 7 mV decay even after 50,000 potential cycles. Remarkably, it exhibits a very low hydrogen peroxide (H2O2) yield (0.07%) at 0.6 V and maintains this performance with negligible change after 10,000 potential cycles. Fuel cells assembled with this cathode PtFe/Fe-N-C catalyst show exceptional durability, with only 8 mV voltage loss at 0.8 A cm-2 after 30,000 cycles and ignorable current degradation at a voltage of 0.6 V over 85 h. Comprehensive in situ experiments and theoretical calculations reveal that oxygen species spillover from Fe-N-C to PtFe alloy not only inhibits H2O2 production but also eliminates harmful oxygenated radicals. This work paves the way for the design of highly efficient and stable ORR catalysts and has significant implications for the development of next-generation fuel cells.

Multi-omics Analysis Reveals Key Gut Microbiota and Metabolites Closely Associated with Huntington's Disease.

Dysbiosis of the gut microbiota is closely associated with neurodegenerative diseases, including Huntington's disease (HD). Gut microbiome-derived metabolites are key factors in host-microbiome interactions. This study aimed to investigate the crucial gut microbiome and metabolites in HD and their correlations. Fecal and serum samples from 11 to 26 patients with HD, respectively, and 16 and 23 healthy controls, respectively, were collected. The fecal samples were used for shotgun metagenomics while the serum samples for metabolomics analysis. Integrated analysis of the metagenomics and metabolomics data was also conducted. Firmicutes, Bacteroidota, Proteobacteria, Uroviricota, Actinobacteria, and Verrucomicrobia were the dominant phyla. At the genus level, the presence of Bacteroides, Faecalibacterium, Parabacteroides, Alistipes, Dialister, and Christensenella was higher in HD patients, while the abundance of Lachnospira, Roseburia, Clostridium, Ruminococcus, Blautia, Butyricicoccus, Agathobaculum, Phocaeicola, Coprococcus, and Fusicatenibacter decreased. A total of 244 differential metabolites were identified and found to be enriched in the glycerophospholipid, nucleotide, biotin, galactose, and alpha-linolenic acid metabolic pathways. The AUC value from the integrated analysis (1) was higher than that from the analysis of the gut microbiota (0.8632). No significant differences were found in the ACE, Simpson, Shannon, Sobs, and Chao indexes between HD patients and controls. Our study determined crucial functional gut microbiota and potential biomarkers associated with HD pathogenesis, providing new insights into the role of the gut microbiota-brain axis in HD occurrence and development.

Integration Construction of Hybrid Electrocatalysts for Oxygen Reduction.

There is notable progress in the development of efficient oxygen reduction electrocatalysts, which are crucial components of fuel cells. However, these superior activities are limited by imbalanced mass transport and cannot be fully reflected in actual fuel cell applications. Herein, the design concepts and development tracks of platinum (Pt)-nanocarbon hybrid catalysts, aiming to enhance the performance of both cathodic electrocatalysts and fuel cells, are presented. This review commences with an introduction to Pt/C catalysts, highlighting the diverse architectures developed to date, with particular emphasis on heteroatom modification and microstructure construction of functionalized nanocarbons based on integrated design concepts. This discussion encompasses the structural evolution, property enhancement, and catalytic mechanisms of Pt/C-based catalysts, including rational preparation recipes, superior activity, strong stability, robust metal-support interactions, adsorption regulation, synergistic pathways, confinement strategies, ionomer optimization, mass transport permission, multidimensional construction, and reactor upgrading. Furthermore, this review explores the low-barrier or barrier-free mass exchange interfaces and channels achieved through the impressive multidimensional construction of Pt-nanocarbon integrated catalysts, with the goal of optimizing fuel cell efficiency. In conclusion, this review outlines the challenges associated with Pt-nanocarbon integrated catalysts and provides perspectives on the future development trends of fuel cells and beyond.

K+-Specification with Flavone P0 Probe in a G-Quadruplex DNA.

G-quadruplex (G4) DNA is considered as a prospective therapeutic target due to its potential biological significance. To understand G4 biological roles and function, a G4-specific fluorescent probe is necessary. However, it is difficult for versatile G4 to precisely recognize without perturbing their folding dynamics. Herein, we reported that flavone P0 can be a fluorescent probe for G4 DNA-specific recognition and have developed a highly selective detection of K+ ion by dimeric G4/P0 system. When comparing various nucleic acid structures, including G4, i-motif, ss/ds-DNA, and triplex, an apparent fluorescence enhancement is observed in the presence of G4 DNA for 85-fold, but only 8-fold for non-G4 DNA. Furthermore, based on fluorescent probe of flavone P0 for G4 DNA screening, the noncovalent dimeric G4/P0 system is exploited as a K+ sensor, that selectively responds to K+ with a 513-fold fluorescence enhancement and a detection range for K+ ion concentration from 0 to 500 mM. This K+ sensor also has a remarkably anti-interference ability for other metal cations, especially for a high concentration of Na+. These results have demonstrated that flavone P0 is an efficient tool for monitoring G-quadruplex DNA and endows flavone P0 with bioanalytical and medicinal applications.

Association of elevated circulating monocyte-platelet aggregates with hypercoagulability in patients with nephrotic syndrome.

BACKGROUND: Hypercoagulability emerges as a central pathological feature and clinical complication in nephrotic syndrome. Increased platelet activation and aggregability are closely related to hypercoagulability in nephrotic syndrome. Monocyte-platelet aggregates (MPAs) have been proposed to represent a robust biomarker of platelet activation. The aim of this study was to investigate levels of the circulating MPAs and MPAs with the different monocyte subsets to evaluate the association of MPAs with hypercoagulability in nephrotic syndrome. METHODS: Thirty-two patients with nephrotic syndrome were enrolled. In addition, thirty-two healthy age and sex matched adult volunteers served as healthy controls. MPAs were identified by CD14 monocytes positive for CD41a platelets. The classical (CD14 + + CD16-, CM), the intermediate (CD14 + + CD16+, IM) and the non-classical (CD14 + CD16++, NCM) monocytes, as well as subset specific MPAs, were measured by flow cytometry. RESULTS: Patients with nephrotic syndrome showed a higher percentage of circulating MPAs as compared with healthy controls (p < 0.001). The percentages of MPAs with CM, IM, and NCM were higher than those of healthy controls (p = 0.012, p < 0.001 and p < 0.001, respectively). Circulating MPAs showed correlations with hypoalbuminemia (r=-0.85; p < 0.001), hypercholesterolemia (r = 0.54; p < 0.001), fibrinogen (r = 0.70; p < 0.001) and D-dimer (r = 0.37; p = 0.003), but not with hypertriglyceridemia in nephrotic syndrome. The AUC for the prediction of hypercoagulability in nephrotic syndrome using MPAs was 0.79 (95% CI 0.68-0.90, p < 0.001). The sensitivity of MPAs in predicting hypercoagulability was 0.71, and the specificity was 0.78. CONCLUSION: Increased MPAs were correlated with hypercoagulability in nephrotic syndrome. MPAs may serve as a potential biomarker for thrombophilic or hypercoagulable state and provide novel insight into the mechanisms of anticoagulation in nephrotic syndrome.

Surface Redox Chemistry Regulates the Reaction Microenvironment for Efficient Hydrogen Peroxide Generation.

Electrosynthesis has emerged as an enticing solution for hydrogen peroxide (H2O2) production. However, efficient H2O2 generation encounters challenges related to the robust gas-liquid-solid interface within electrochemical reactors. In this work, we introduce an effective hydrophobic coating modified by iron (Fe) sites to optimize the reaction microenvironment. This modification aims to mitigate radical corrosion through Fe(II)/Fe(III) redox chemistry, reinforcing the reaction microenvironment at the three-phase interface. Consequently, we achieved a remarkable yield of up to 336.1 mmol h-1 with sustained catalyst operation for an extensive duration of 230 h at 200 mA cm-2 without causing damage to the reaction interface. Additionally, the Faradaic efficiency of H2O2 exceeded 90% across a broad range of test current densities. This surface redox chemistry approach for manipulating the reaction microenvironment not only advances long-term H2O2 electrosynthesis but also holds promise for other gas-starvation electrochemical reactions.