Combination of prostate volume and apparent diffusion coefficient can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies.

BACKGROUND: Nowadays, there are many patients who undergo unnecessary prostate biopsies after receiving a prostate imaging reporting and data system (PI-RADS) score of 3. Our purpose is to identify cutoff values of the prostate volume (PV) and minimum apparent diffusion coefficient (ADCmin) to stratify those patients to reduce unnecessary prostate biopsies. METHODS: Data from 224 qualified patients who received prostate biopsies from January 2019 to June 2023 were collected. The Mann-Whitney U test was used to compare non-normal distributed continuous variables, which were recorded as median (interquartile ranges). The correlation coefficients were calculated using Spearman's rank correlation analysis. Categorical variables are recorded by numbers (percentages) and compared by χ2 test. Both univariate and multivariate logistic regression analysis were used to determine the independent predictors. The receiver-operating characteristic curve and the area under the curve (AUC) were used to evaluate the diagnostic performance of clinical variables. RESULTS: Out of a total of 224 patients, 36 patients (16.07%) were diagnosed with clinically significant prostate cancer (csPCa), whereas 72 patients (32.14%) were diagnosed with any grade prostate cancer. The result of multivariate analysis demonstrated that the PV (p < 0.001, odds ratio [OR]: 0.952, 95% confidence interval [95% CI]: 0.927-0.978) and ADCmin (p < 0.01, OR: 0.993, 95% CI: 0.989-0.998) were the independent factors for predicting csPCa. The AUC values of the PV and ADCmin were 0.779 (95% CI: 0.718-0.831) and 0.799 (95% CI: 0.740-0.849), respectively, for diagnosing csPCa. After stratifying patients by PV and ADCmin, 24 patients (47.06%) with "PV < 55 mL and ADCmin < 685 µm2/s" were diagnosed with csPCa. However, only one patient (1.25%) with PV ≥ 55 mL and ADCmin ≥ 685 µm2/s were diagnosed with csPCa. CONCLUSIONS: In this study, we found the combination of PV and ADCmin can stratify patients with a PI-RADS score of 3 to reduce unnecessary prostate biopsies. These patients with "PV ≥ 55 mL and ADCmin ≥ 685 µm2/s" may safely avoid prostate biopsies.

[Research progress in pharmacological effects of Gypsum Fibrosum and material basis for its heat-clearing effect].

Gypsum Fibrosum, as a classic heat-clearing medicine, is widely used in the clinical practice of traditional Chinese medicine(TCM). However, debates exist about the material basis and mechanism of its efficacy. Therefore, this paper reviewed the recent research progress in the heat-clearing effect and mechanism of Gypsum Fibrosum and discussed the material basis for the heat-clearing effect of this medicine. Ca~(2+) may inhibit the upward movement of temperature set point by regulating the Na~+/Ca~(2+) level in the heat-regulating center. Moreover, trace elements may inhibit the rise of body temperature by regulating the immune system, promoting the absorption of Ca~(2+), and affecting the synthesis of prostaglandin E2(PGE2). This review aims to enrich the knowledge about the mechanism of Gypsum Fibrosum in clearing heat and provides a scientific basis for the clinical application and further development of Gypsum Fibrosum.

Coupling of Electric and Flow Fields to Enhance Ion Transport for Energy-Efficient Electrochemical Tap-Water Softening.

Electrochemical-induced precipitation is a sustainable approach for tap-water softening, but the hardness removal performance and energy efficiency are vastly limited by the ultraslow ion transport and the superlow local HCO3-/Ca2+ ratio compared to the industrial scenarios. To tackle the challenges, we herein report an energy-efficient electrochemical tap-water softening strategy by utilizing an integrated cathode-anode-cathode (CAC) reactor in which the direction of the electric field is reversed to that of the flow field in the upstream cell, while the same in the downstream cell. As a result, the transport of ions, especially HCO3-, is significantly accelerated in the downstream cell under a flow field. The local HCO3-/Ca2+ ratio is increased by 1.5 times, as revealed by the finite element numerical simulation and in situ imaging. In addition, a continuous flow electrochemical system with an integrated CAC reactor is operated for 240 h to soften tap water. Experiments show that a much lower cell voltage (9.24 V decreased) and energy consumption (28% decreased) are obtained. The proposed ion-transport enhancement strategy by coupled electric and flow fields provides a new perspective on developing electrochemical technologies to meet the flexible and economic demand for tap-water softening.

Study on the role of CCM3 gene and lead exposure induced neurotoxicity through neurovascular units.

This study aimed to determine the toxic effects of vascular CCM3 gene deficiency and lead (Pb) exposure on the nervous system. Lentiviral transfection was performed to generate a stable strain of brain microvascular endothelial cells with low CCM3 expression. MTT assay assessed the survival rate of cells exposed to Pb, determining the dose and duration of Pb exposure in vitro. Proteomic analysis was performed on the differentially expressed proteins in bEnd3 and HT22 cells and flow cytometry was used to detect cell apoptosis. Finally, urine samples from pregnant and postpartum women were subjected to ICP-MS to detect Pb levels and HPLC to detect neurotransmitter metabolites. Based on the proteomic analysis of bEnd3 (CCM3-/-) cells co-cultured with HT22 cells, it was determined that HT22 cells and CCM3 genes interfered with bEnd3 cell differential proteins,2 including apoptosis and ferroptosis pathways. Electron microscopy observation, ICP-MS iron ion loading detection, and WB determination of protein GPX4 expression confirmed that HT22 cells undergo apoptosis, while bEnd3 cells undergo multiple pathways of iron death and apoptosis regulation. Furthermore, a linear regression model showed the interaction between maternal urine Pb levels, the rs9818496 site of the CCM3 SNP in peripheral blood DNA, and the concentration of the neurotransmitter metabolite 5-HIAA in maternal urine (F=4.198, P < 0.05). bEnd3 cells with CCM3 gene deficiency can induce HT22 cell apoptosis through iron death and apoptosis pathways under Pb exposure in a combined cell culture Pb exposure model, and CCM3 gene deficiency in endothelial cells and Pb exposure interacts with neural cell HT22. Epidemiological studies on maternal and newborn infants further confirmed the interaction between urine Pb levels in mothers and the SNP rs9818496 site of the CCM3 gene in peripheral blood DNA.

High-Performance Solar-Blind Photodetector Based on (010)-Plane ß-Ga2O3 Thermally Oxidized from Nonpolar (110)-Plane GaN.

A high-performance planar structure metal-semiconductor-metal-type solar-blind photodetector (SBPD) was fabricated on the basis of (010)-plane ß-Ga2O3 thermally oxidized from nonpolar (110)-plane GaN. A full width at half maximum of 0.486° was achieved for the X-ray rocking curve associated with (020)-plane ß-Ga2O3, which is better than most reported results for the heteroepitaxially grown (-201)-plane ß-Ga2O3. As a result of the relatively high crystalline quality, a dark current as low as 6.30 × 10-12 A was achieved at 5 V, while the photocurrent reached 1.86 × 10-5 A under 254 nm illumination at 600 µW/cm2. As a result, the photo-to-dark current ratio, specific detectivity, responsivity, and external quantum efficiency were calculated to be 2.95 × 106, 2.39 × 1012 Jones, 3.72 A/W, and 1815%, respectively. Moreover, the SBPD showed excellent repeatability and stability in the time-dependent photoresponse characteristics with fast relaxation time constants for the rise and decay processes of only 0.238 and 0.062 s, respectively. This study provides a promising approach to fabricate the device-level (010)-plane ß-Ga2O3 film and a new way for the epitaxial growth of (010)-plane ß-Ga2O3 and (110)-plane GaN as mutual substrates.

Neutrophil extracellular traps promote acetaminophen-induced acute liver injury in mice via AIM2.

Excessive acetaminophen (APAP) can induce neutrophil activation and hepatocyte death. Along with hepatocyte dysfunction and death, NETosis (a form of neutrophil-associated inflammation) plays a vital role in the progression of acute liver injury (ALI) induced by APAP overdose. It has been shown that activated neutrophils tend to migrate towards the site of injury and participate in inflammatory processes via formation of neutrophil extracellular traps (NETs). In this study we investigated whether NETs were involved in hepatocyte injury and contributed to APAP-induced ALI progression. ALI mouse model was established by injecting overdose (350 mg/kg) of APAP. After 24 h, blood and livers were harvested for analyses. We showed that excessive APAP induced multiple programmed cell deaths of hepatocytes including pyroptosis, apoptosis and necroptosis, accompanied by significantly increased NETs markers (MPO, citH3) in the liver tissue and serum. Preinjection of DNase1 (10 U, i.p.) for two consecutive days significantly inhibited NETs formation, reduced PANoptosis and consequently alleviated excessive APAP-induced ALI. In order to clarify the communication between hepatocytes and neutrophils, we induced NETs formation in isolated neutrophils, and treated HepaRG cells with NETs. We found that NETs treatment markedly increased the activation of GSDMD, caspase-3 and MLKL, while pre-treatment with DNase1 down-regulated the expression of these proteins. Knockdown of AIM2 (a cytosolic innate immune receptor) abolished NETs-induced PANoptosis in HepaRG cells. Furthermore, excessive APAP-associated ALI was significantly attenuated in AIM2KO mice, and PANoptosis occurred less frequently. Upon restoring AIM2 expression in AIM2KO mice using AAV9 virus, both hepatic injury and PANoptosis was aggravated. In addition, we demonstrated that excessive APAP stimulated mtROS production and mitochondrial DNA (mtDNA) leakage, and mtDNA activated the TLR9 pathway to promote NETs formation. Our results uncover a novel mechanism of NETs and PANoptosis in APAP-associated ALI, which might serve as a therapeutic target.

Photocatalytic oxidation of formaldehyde under visible light using BiVO4-TiO2 synthesized via ultrasonic blending.

Formaldehyde (HCHO) is one of the primary indoor air pollutants, and efficiently eliminating it, especially at low concentrations, remains challenging. In this study, BiVO4-TiO2 catalyst was developed using ultrasonic blending technology for the photocatalytic oxidation of low-level indoor HCHO. The crystal structure, surface morphology, element distribution, and active oxidation species of the catalyst were examined using XRD, SEM, TEM, UV-Vis, EDS, and ESR techniques. Our results demonstrated that the BiVO4-TiO2 catalyst, prepared by ultrasonic blending, exhibited good oxidation performance and stability. The HCHO concentration reduced from 1.050 to 0.030 mg/m3 within 48 h, achieving a removal rate of 97.1%. The synergy between BiVO4 and TiO2 enhanced the efficiency of separating photogenerated carriers and minimized the likelihood of recombination between photogenerated electrons and holes. Additionally, this synergy significantly enhanced the presence of hydroxyl radicals (·OH) on the catalyst, resulting in an oxidation performance superior to that of either BiVO4 or TiO2. Our research offers valuable insights for the development of new photocatalysts to address HCHO pollution.

Modulators targeting protein-protein interactions in Mycobacterium tuberculosis.

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis), mainly transmitted through droplets to infect the lungs, and seriously affecting patients' health and quality of life. Clinically, anti-TB drugs often entail side effects and lack efficacy against resistant strains. Thus, the exploration and development of novel targeted anti-TB medications are imperative. Currently, protein-protein interactions (PPIs) offer novel avenues for anti-TB drug development, and the study of targeted modulators of PPIs in M. tuberculosis has become a prominent research focus. Furthermore, a comprehensive PPI network has been constructed using computational methods and bioinformatics tools. This network allows for a more in-depth analysis of the structural biology of PPIs and furnishes essential insights for the development of targeted small-molecule modulators. Furthermore, this article provides a detailed overview of the research progress and regulatory mechanisms of PPI modulators in M. tuberculosis, the causative agent of TB. Additionally, it summarizes potential targets for anti-TB drugs and discusses the prospects of existing PPI modulators.

Relationship Between Heart Rate Variability Parameters and Short-Term Prognosis of Patients with Acute Myocardial Infarction.

OBJECTIVE: To determine the link between heart rate variability (HRV) and short-term adverse outcomes (re-hospitalisation or death due to cardiac arrhythmia, recurrent myocardial infarction, heart failure, all-cause death) in acute myocardial infarction (AMI). STUDY DESIGN: A descriptive study. Place and Duration of the Study: Department of Cardiovascular Medicine, The First Affiliated Hospital of Anhui Medical University, China, from January 2018 to December 2021. METHODOLOGY: Clinical data of 245 patients diagnosed with AMI were retrospectively analysed. After discharge from the hospital, patients were followed for a year and categorised into two groups based on the occurrence of adverse events: the adverse event group (n=82) and the no adverse event group (n=163). Differences in clinical characteristics were compared, independent factors influencing adverse events were analysed, and diagnostic efficacy was assessed. RESULTS: Univariate analysis showed age, hyperlipidaemia, specific HRV parameters (SDNN, SDANN, RMSSD, PNN50, LF/HF), and myocardial injury markers (CK-MB, cTnI, NT-proBNP) as associated with these events (all p < 0.05). Multivariable analysis revealed decreased SDNN, decreased SDANN, increased LF/HF, and elevated levels of CK-MB, cTnI, and NT-proBNP as independent influences. Both HRV parameters and myocardial injury markers were reliable predictors on ROC curve analysis. The highest diagnostic efficacy was achieved by combining these predictors. CONCLUSION: AMI patients frequently experience short-term adverse events. Both HRV parameters and myocardial injury markers, which demonstrate significant predictive efficacy, independently influence these outcomes. KEY WORDS: Acute myocardial infarction, Coronary angiography, Heart rate variability, Myocardial injury, Risk factors.

Mechanical Behavior of Bio-Inspired Honeycomb-Core Composite Sandwich Structures to Low-Velocity Dynamic Loading.

In order to improve the impact resistance of sandwich panels under low-velocity impact, the lotus leaf vein is selected as a biological prototype to design a bio-inspired honeycomb (BIH) sandwich panel. ABAQUS is used to establish and effectively verify the finite element (FE) model of the BIH sandwich panel. To systematically compare and study the mechanical properties of BIH and conventional hexagonal honeycomb sandwich panels under low-velocity impact, the maximum displacement of face-sheets, the deformation mode, the plastic energy consumption and the dynamic response curve of the impact end are presented. At the same time, the performance differences between them are revealed from the perspective of an energy absorption mechanism. Furthermore, the influence of the circumscribed circle diameter ratio of the BIH trunk to branch (γ), the thickness ratio of the trunk to branch (K) and the impact angle (θ) on impact resistance is studied. Finally, the BIH sandwich panel is further optimized by using the response surface method. It can be concluded that, compared to conventional hexagonal honeycomb sandwich panels, the addition of walls in the BIH sandwich panel reduces the maximum deformation of the rear face-sheet by 10.29% and increases plastic energy consumption by 8.02%. Properly adjusting the structural parameters can effectively enhance the impact resistance of the BIH sandwich panel.

Unconventional Superconducting Diode Effects via Antisymmetry and Antisymmetry Breaking.

Symmetry breaking plays a pivotal role in unlocking intriguing properties and functionalities in material systems. For example, the breaking of spatial and temporal symmetries leads to a fascinating phenomenon: the superconducting diode effect. However, generating and precisely controlling the superconducting diode effect pose significant challenges. Here, we take a novel route with the deliberate manipulation of magnetic charge potentials to realize unconventional superconducting flux-quantum diode effects. We achieve this through suitably tailored nanoengineered arrays of nanobar magnets on top of a superconducting thin film. We demonstrate the vital roles of inversion antisymmetry and its breaking in evoking unconventional superconducting effects, namely a magnetically symmetric diode effect and an odd-parity magnetotransport effect. These effects are nonvolatilely controllable through in situ magnetization switching of the nanobar magnets. Our findings promote the use of antisymmetry (breaking) for initiating unconventional superconducting properties, paving the way for exciting prospects and innovative functionalities in superconducting electronics.

A comparative study of diffusion kurtosis imaging and diffusion tensor imaging in detecting corticospinal tract impairment in diffuse glioma patients.

PURPOSE: This study aimed to investigate the diagnostic performance of diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) in identifying aberrations in the corticospinal tract (CST), whilst elucidating the relationship between abnormalities of CST and patients' motor function. METHODS: Altogether 21 patients with WHO grade II or grade IV glioma were enrolled and divided into Group 1 and Group 2, according to the presence or absence of preoperative paralysis. DKI and DTI metrics were generated and projected onto the CST. Histograms of the CST along x, y, and z axes were developed based on DKI and DTI metrics, and compared subsequently to determine regions of aberrations on the fibers. The receiver operating characteristic curve was performed to investigate the diagnostic efficacy of DKI and DTI metrics. RESULTS: In Group 1, a significantly lower fractional anisotropy, radial kurtosis and mean kurtosis, and a higher mean diffusivity were found in the ipsilateral CST as compared to the contralateral CST. Significantly higher relative axial diffusivity, relative radial diffusivity, and relative mean diffusivity (rMD) were found in Group 1, as compared to Group 2. The relative volume of ipsilateral CST abnormalities higher than the maximum value of mean kurtosis combined with rMD exhibited the best diagnostic performance in distinguishing dysfunction of CST with an AUC of 0.93. CONCLUSION: DKI is sensitive in detecting subtle changes of CST distal from the tumor. The combination of DKI and DTI is feasible for evaluating the impairment of the CST.

Genomic structure analysis and construction of DNA fingerprint for four sheep populations.

The Yongdeng Qishan sheep (QS) is a sheep population found locally in China. To gain in-depth knowledge of its population characteristics, three control groups were chosen, comprising the Lanzhou fat-tailed sheep (LFT), TAN sheep (TAN), and Minxian black fur sheep (MBF), inhabiting the nearby environments. This study genotyped a total of 120 individuals from four sheep populations: QS, LFT, TAN, and MBF. Using Specific-Locus Amplified Fragment Sequencing, we conducted genetic diversity, population structure, and selective sweep analysis, and constructed the fingerprint of each population. In total, there were 782 535 single nucleotide polymorphism (SNP) variations identified, with most being situated within regions that are intergenic or intronic. The genetic diversity analysis revealed that the QS population exhibited lower genetic diversity compared to the other three populations. Consistent results were obtained from the principal component, phylogenetic tree, and population structure analysis, indicating significant genetic differences between QS and the other three populations. However, a certain degree of differentiation was observed within the QS population. The linkage disequilibrium (LD) patterns among the four populations showed clear distinctions, with the QS group demonstrating the most rapid LD decline. Kinship analysis supported the findings of population structure, dividing the 90 QS individuals into two subgroups consisting of 23 and 67 individuals. Selective sweep analysis identified a range of genes associated with reproduction, immunity, and adaptation to high-altitude hypoxia. These genes hold potential as candidate genes for marker-assisted selection breeding. Additionally, a total of 86 523 runs of homozygosity (ROHs) were detected, showing non-uniform distribution across chromosomes, with chromosome 1 having the highest coverage percentage and chromosome 26 the lowest. In the high-frequency ROH islands, 79 candidate genes were associated with biological processes such as reproduction and fat digestion and absorption. Furthermore, a DNA fingerprint was constructed for the four populations using 349 highly polymorphic SNPs. In summary, our research delves into the genetic diversity and population structure of QS population. The construction of DNA fingerprint profiles for each population can provide valuable references for the identification of sheep breeds both domestically and internationally.

Monolithic Integration of GaN-Based Transistors and Micro-LED.

Micro-LED is considered an emerging display technology with significant potential for high resolution, brightness, and energy efficiency in display applications. However, its decreasing pixel size and complex manufacturing process create challenges for its integration with driving units. Recently, researchers have proposed various methods to achieve highly integrated micro-structures with driving unit. Researchers take advantage of the high performance of the transistors to achieve low power consumption, high current gain, and fast response frequency. This paper gives a review of recent studies on the new integration methods of micro-LEDs with different types of transistors, including the integration with BJT, HEMT, TFT, and MOSFET.

A novel microglia-targeting strategy based on nanoparticle-mediated delivery of miR-26a-5p for long-lasting analgesia in chronic pain.

Accumulating evidence supports the notion that microglia play versatile roles in different chronic pain conditions. However, therapeutic strategies of chronic pain by targeting microglia remain largely overlooked. This study seeks to develop a miRNA-loaded nano-delivery system by targeting microglia, which could provide a decent and long-lasting analgesia for chronic pain. Surface aminated mesoporous silica nanoparticles were adopted to load miR-26a-5p, a potent analgesic miRNA, by electrostatic adsorption, which can avoid miR-26a-5p is rapidly released and degraded. Then, targeting peptide MG1 was modified on the surface of aminated mesoporous silica particles for microglia targeting. In peripheral nerve injury induced neuropathic pain model, a satisfactory anti-allodynia effect with about 6 weeks pain-relief duration were achieved through targeting microglia strategy, which decreased microglia activation and inflammation by Wnt5a, a non-canonical Wnt pathway. In inflammatory pain and chemotherapy induced peripheral neuropathic pain, microglia targeting strategy also exhibited more efficient analgesia and longer pain-relief duration than others. Overall, we developed a microglia-targeting nano-delivery system, which facilitates precisely miR-26a-5p delivery to enhance analgesic effect and duration for several chronic pain conditions.

Local O2 concentrating boosts the electro-Fenton process for energy-efficient water remediation.

The electro-Fenton process is a state-of-the-art water treatment technology used to remove organic contaminants. However, the low O2 utilization efficiency (OUE, <1%) and high energy consumption remain the biggest obstacles to practical application. Here, we propose a local O2 concentrating (LOC) approach to increase the OUE by over 11-fold compared to the conventional simple O2 diffusion route. Due to the well-designed molecular structure, the LOC approach enables direct extraction of O2 from the bulk solution to the reaction interface; this eliminates the need to pump O2/air to overcome the sluggish O2 mass transfer and results in high Faradaic efficiencies (~50%) even under natural air diffusion conditions. Long-term operation of a flow-through pilot device indicated that the LOC approach saved more than 65% of the electric energy normally consumed in treating actual industrial wastewater, demonstrating the great potential of this system-level design to boost the electro-Fenton process for energy-efficient water remediation.

Tubule-specific cyclin-dependent kinase 12 knockdown potentiates kidney injury through transcriptional elongation defects.

Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor, and the potential mechanism is not well understood. Here, we found that CDK12 was downregulated in the renal tubular epithelial cells in both patients with AKI and murine AKI models. Moreover, tubular cell-specific knockdown of CDK12 in mice enhanced cisplatin-induced AKI through promotion of genome instability, apoptosis, and proliferative inhibition, whereas CDK12 overexpression protected against AKI. Using the single molecule real-time (SMRT) platform on the kidneys of CDK12RTEC+/- mice, we found that CDK12 knockdown targeted Fgf1 and Cast through transcriptional elongation defects, thereby enhancing genome instability and apoptosis. Overall, these data demonstrated that CDK12 knockdown could potentiate the development of AKI by altering the transcriptional elongation defect of the Fgf1 and Cast genes, and more attention should be given to patients treated with CDK12 inhibitors to prevent AKI.

Synergetic surface enhancement of quantum dots-based electrochemiluminescence with photonic crystal light scattering and metal surface plasmon resonance for sensitive bioanalysis.

Noble metal nanostructures and photonic crystals (PhCs) have been widely investigated as substrates for constructing surface enhanced electrochemiluminescence (SE-ECL) biosensors. However, their applications are hindered by the limited enhancement intensity of surface plasmon resonance (SPR) and an incomplete mechanism for the photonic enhancement effect. Hence, developing a novel SE-ECL strategy with better signal enhanced capability and enriching our understanding of the intrinsic mechanisms for efficient bioanalysis is extremely urgent. Here, a synergistic SE-ECL strategy was developed for the sensitive determination of prostate specific antigen (PSA) protein. The randomly arranged polystyrene (r-PS) spheres and PS PhC arrays were applied to enhance the ECL emission of cadmium sulfide quantum dots (CdS QDs) and the results suggested that the PhC arrays displayed superior intensity (0.22) than the r-PS interface (0.10). Au nanoparticles (NPs) were introduced onto the two kinds of surfaces and further boosted the ECL intensity. According to the ECL measurements, Au NPs modified at the r-PS surface exhibited only a slight increase (0.13), while the PhC arrays showed approximately 5-fold enhancement (0.92), benefiting from the synergistic enhancement. The finite-difference time-domain (FDTD) simulation indicated that the ECL enhancement was ascribed to the coupled electromagnetic (EM) field at the surfaces of PS PhCs and Au NPs. The SE-ECL could achieve a detection range from 1 pg/mL to 1 µg/mL with a detection limit of 0.41 pg/mL (S/N = 3). This study provides the first combination of PhC arrays and metal surface plasmon nanostructure for the synergetic enhancement of SE-ECL systems. It opens a new avenue for the rational design of advanced ECL biosensors and shows great perspective for clinical diagnosis.

Osthole Activates the Cholinergic Anti-Inflammatory Pathway via α7nAChR Upregulation to Alleviate Inflammatory Responses.

Osthole (also known as Osthol) is the main anti-inflammatory coumarin found in Cnidium monnieri and severs as the exclusive quality-controlled component according the Chinese Pharmacopoeia. However, its underlying anti-inflammatory mechanism remains unknown. In this study, we demonstrated that Osthole treatment significantly inhibited the generation of TNF-α, but not IL-6 in the classical LPS-stimulated RAW264.7 macrophage model. In addition, LPS induced the activation of both MAPK and NF-κB signalling pathways, of which the former was dose-dependently restrained by Osthole via suppressing the phosphorylation of JNK and P38 proteins, while the phosphorylation of IκB and P65 proteins remained unaffected. Interestingly, Osthole dose-dependently up-regulated the expression of the key cholinergic anti-inflammatory pathway regulator α7nAChR, and the TNF-α inhibition effect of Osthole was also significantly alleviated by the treatment of α7nAChR antagonist methylbetaine. These results demonstrate that Osthole may regulate TNF-α by promoting the expression of α7nAChR, thereby activate the vagus nerve-dependent cholinergic anti-inflammatory pathway.

Serum Cystatin C as a Risk Factor for Supratherapeutic Digoxin Concentration in Elderly Patients with Heart Failure and Chronic Kidney Disease.

BACKGROUND: Digoxin is primarily metabolized by the kidney, and its toxicity is strongly associated with high concentrations, particularly in elderly patients. The purpose of this study was to evaluate the predictive performance of renal function biomarkers for supratherapeutic digoxin concentrations in elderly patients with heart failure (HF) and chronic kidney disease (CKD). METHODS: Data were retrospectively obtained from elderly patient with HF and CKD who received digoxin treatment from January 2022 and December 2022. Logistic regression was used to assess independent risk factors for supratherapeutic concentrations. The predictive performance of serum creatinine, serum cystatin C, and blood urea nitrogen on supratherapeutic concentrations was compared by receiver operating characteristic analysis. RESULTS: A total of 115 elderly patients with HF and CKD were enrolled in our study. Supratherapeutic concentrations were detected in 49 patients. Logistic regression analysis showed that estimated glomerular filtration rate calculated by serum cystatin C [eGFRCysC, odds ratio (OR): 0.962, P = 0.006], heart rate (OR: 1.024, P = 0.040), and NYHA class (OR: 3.099, P = 0.010) were independent risk factors for supratherapeutic concentration. Cutoff value for eGFRCysC between the two groups was 41 ml/min/1.73m2. Predictive performance of serum cystatin C was further improved in patients with obesity, CKD stage 4-5, and older than 75 years compared with normal weight, CKD stage 3, and aged 60-75-year-old patients. CONCLUSIONS: Serum cystatin C is a sensitive renal function biomarker to predict supratherapeutic digoxin concentration in elderly patients with HF and CKD.