Systemic immune inflammation index and all-cause mortality in chronic kidney disease: A prospective cohort study.

BACKGROUND: The aim of this study was to investigate the association between systemic immune-inflammation index (SII) and all-cause mortality in individuals with chronic kidney disease (CKD). PATIENTS AND METHODS: This prospective cohort study was carried out among 9303 participants with CKD from the National Health and Nutrition Examination Survey cycles spanning 1999 to 2018. The mortality data were ascertained by linking participant records to the National Death Index up to December 31, 2019. Complex sampling-weighted multivariate Cox proportional hazards models were employed to estimate the association between SII level and all-cause mortality, providing hazard ratios (HR) and 95% confidence intervals (CI). A restricted cubic spline analysis was conducted to explore potential nonlinear correlation. Subgroup analyses and sensitivity analyses were also conducted. RESULTS: During a median follow-up period of 86 months, 3400 (36.54%) all-cause deaths were documented. A distinctive "J"-shaped relationship between SII level and all-cause mortality was discerned among individuals with CKD, with the nadir observed at an SII level of 478.93 within the second quartile. After adjusting for potential covariates, the risk of all-cause mortality escalated by 13% per increment of one standard deviation of SII, once SII exceeded 478.93 (HR = 1.13; 95% CI = 1.08-1.18). An elevated SII was associated with an increased risk of all-cause mortality among patients with CKD (Q4 vs. Q2: HR = 1.23; 95% CI = 1.01-1.48). Subgroup analyses indicated that the correlation between SII and CKD mortality was particularly pronounced among participants over 60 years old and individuals with diabetes. Sensitivity analyses revealed a linear positive association between SII and all-cause mortality after removing the extreme 5% outliers of SII. CONCLUSIONS: A distinctive "J"-shaped relationship between SII level and all-cause mortality was identified among individuals with CKD. Further research is warranted to validate and expand upon these findings.

Photomodulation of Charge Transfer through Excited-State Processes: Directing Donor-Acceptor Binding Dynamics.

Modulating charge transfer (CT) interactions between donor and acceptor molecules may give rise to unique dynamic changes in physicochemical properties, exhibiting great importance in supramolecular chemistry and materials science. In this work, we demonstrate the first instance of reversible photomodulation of donor-acceptor (D-A) CT interaction in the solid state.Pyridinium-based chromophore featuring π-conjugated D-A structures can not only function as a good electron acceptor to undergo photoinduced electron transfer (ET) or engage in intermolecular CT interaction, but also exhibit unique dual emission depending on the excitation wavelengths. The rotatable C-C single bonds within D-A pairs enhance the tunability of molecular structure. Through the synergy of a photoinduced ET and an excited-state conformational change, the intermolecular CT interaction can be switched on and off by alternate light irradiation to enables reversibly modulation of the affinity between donor and acceptor molecules, accompanied by visual color switching and fluorescence on-off as feedback signals.

[Effects of exogenous 6-BA on flag leaf physiology, yield, and quality of wheat after low temperature stress at booting stage]. / 外源6-BA对孕穗期低温胁迫后小麦旗叶生理、产量及品质的影响.

Low temperature (LT) in spring usually occurs at the booting of winter wheat, resulting in reduction of wheat yield. In this study, we used the LT-sensitive wheat cultivar 'Wanmai 52' and the LT-insensitive wheat cultivar 'Yannong 19' as experimental materials to conduct LT treatment (-2 ℃ and 0 ℃) at booting stage. After the LT treatment, we sprayed 6-benzylaminoadenine (6-BA) solutions with concentrations of 10, 20, and 30 mg·L-1 respectively, with equal mass distilled water as control to investigate the effects of spraying 6-BA on the physiological characteristics, yield and quality of wheat flag leaves after LT stress at booting stage. The results showed that compared with the control, young ear of wheat treated with exogenous spraying 6-BA was fuller, the floret morphology was improved, and the number of vascular bundles under the spike was increased. 6-BA application promoted the accumulation of soluble sugar, soluble protein, and proline in flag leaves. The activities of peroxidase and superoxide dismutase were increased, and the content of malondialdehyde was decreased. Exogenous 6-BA application decreased the number of degenerated spikes of wheat, increased the number of grains per spike and 1000-grain weight, as well as the contents of grain protein, wet gluten, and sedimentation value. In summary, exogenous 6-BA application could effectively alleviate the effects of LT stress on flag leaf and yield of wheat. Under the conditions of this experiment, the mitigation effect of spraying 6-BA solution on Yannong 19 was higher than that of Wanmai 52, and the mitigation effect of spraying 20 mg·L-1 6-BA solution on low temperature stress was the best.

Self-Aligned Ionic Doping of TiO2 Thin-Film Transistors for Enhanced Current Drivability via Postfabrication Superacid Treatment.

Oxide semiconductor thin-film transistors (TFTs) have shown great potential in emerging applications such as flexible displays, radio-frequency identification tags, sensors, and back-end-of-line compatible transistors for monolithic 3D integration beyond their well-established flat-plane display technology. To meet the requirements of these appealing applications, high current drivability is essential, necessitating exploration in materials science and device engineering. In this work, we report for the first time on a simple solution-based superacid (SA) treatment to enhance the current drivability of top-gate TiO2 TFTs with a gate-offset structure. The on-current of these transistors is limited by the relatively low mobility of TiO2 due to its d-orbital conduction nature. It is found that the on-current of TiO2 TFTs is nearly doubled via a quick dip in a SA solution at room temperature in ambient air. A series of experiments, including comparative I-V measurements of TFTs with different treatments and gate structures, C-V measurements, X-ray photoelectron spectroscopy, time-of-flight secondary ion mass spectrometry, and device simulation, were performed to uncover the underlying reason for the current enhancement. It is believed that the protons (H+) from SA are doped into the offset region of TiO2 TFTs, forming an electron double layer and thus boosting the on-current, with the top gate serving as a self-aligned mask for ionic doping. Furthermore, the ionic size and the proportion of the offset region to the channel play crucial roles in the effectiveness of ionic doping, while the position of the incorporated ions, whether in the channel or dielectric, may result in distinct shifts in the turn-on voltage (VON) and affect the functionality of ionic doping. This study provides a pathway for enhancing the current drivability of TiO2 TFTs via selective ionic doping enabled by SA treatment and deepens our understanding of ion incorporation in electronic devices. This approach could be applicable to other material systems and may also benefit TFTs with miniaturized dimensions, thus opening up unprecedented opportunities for TiO2 TFTs in future applications requiring high current drivability.

Promoting the healing of infected diabetic wound by nanozyme-containing hydrogel with anti-bacterial inflammation suppressing, ROS-scavenging and oxygen-generating properties.

Bacterial infections already pose a significant threat to skin wounds, especially in diabetic patients who have difficulty healing wounds. However, wound or bacterial infections are known to produce excess reactive oxygen species (ROS), and hypoxia may further hinder wound healing and the development of chronic wounds. In this study, a multifunctional hydrogel for ROS scavenging and bacterial inhibition was developed by cross-linking polyvinyl alcohol (PVA) and sodium alginate (SA) with graphene oxide (GO) loaded with silver-platinum hybrid nanoparticles (GO@Ag-Pt). The PVA/SA hydrogel loaded with GO@Ag-Pt exhibited the ability to scavenge different types of ROS, generate O2, and kill a broad spectrum of bacteria in vitro. The silver-platinum hybrid nanoparticles significantly increased the antibacterial ability against Escherichia coli and Staphylococcus aureus compared with silver nanoparticles (AgNps). GO@Ag-Pt loaded hydrogel was effective in treating infections caused by S.aureus, thereby significantly promoting wound healing during the inflammatory phase. Hydrogel therapy significantly reduced the level of ROS and alleviated inflammation levels. Notably, our ROS-scavenging, antibacterial hydrogels can be used to effectively treat various types of wounds, including difficult-to-heal diabetic wounds with bacterial infections. Thus, this study proposes an effective strategy for various chronic wound healing based on ROS clearance and bacteriostatic hydrogels.

Dense object detection methods in RAW UAV imagery based on YOLOv8.

Accurate, fast and lightweight dense target detection methods are highly important for precision agriculture. To detect dense apricot flowers using drones, we propose an improved dense target detection method based on YOLOv8, named D-YOLOv8. First, we introduce the Dense Feature Pyramid Networks (D-FPN) to enhance the model's ability to extract dense features and Dense Attention Layer (DAL) to focus on dense target areas, which enhances the feature extraction ability of dense areas, suppresses features in irrelevant areas, and improves dense target detection accuracy. Finally, RAW data are used to enhance the dataset, which introduces additional original data into RAW images, further enriching the feature input of dense objects. We perform validation on the CARPK challenge dataset and constructed a dataset. The experimental results show that our proposed D-YOLOv8m achieved 98.37% AP, while the model parameters were only 13.2 million. The improved network can effectively support any task of dense target detection.

[Mechanism of Liangfang Wenjing Decoction in treatment of hypoxia on endometriosis with cold coagulation and blood stasis by regulating CHCHD4 expression].

To explore the mechanism of Liangfang Wenjing Decoction regulating coiled-coil-helix coiled-coil-helix domain containing 4(CHCHD4) in the treatment of hypoxia on endometriosis(EMs) with cold coagulation and blood stasis. The rat model of cold coagulation and blood stasis syndrome was prepared by the ice-water bath method, and then the EMs model was established by autologous intimal transplantation. The rats were randomly divided into model group, low, medium, and high(4.7, 9.4, and 18.8 g·kg~(-1)) dose groups of Liangfang Wenjing Decoction, Shaofu Zhuyu Decoction group, and sham group, with 10 rats in each group. The rats were given intragastric administration for four weeks. During the modeling, the general condition and vaginal smear of rats were observed, and the blood flow of ears and uterus were detected by laser speckle contrast imaging(LSCI) to judge the syndrome of cold coagulation and blood stasis. After the administration, the general condition of the rats was observed, and the area of ectopic lesions was measured by caliper. The localization and expression of CHCHD4 and hypoxia inducible factors-1α(HIF-1α) were detected by immunohistochemistry, and the mRNA and protein expressions of CHCHD4 and HIF-1α were detected by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot. The primary culture of ectopic endometrial stromal cells(ESCs) from EMs patients was performed, and the CHCHD4 overexpression plasmid was constructed and transfected to establish the ESCs model of CHCHD4 overexpression. The cells were divided into the control group, CHCHD4 overexpression group, CHCHD4 overexpression+control serum group, and CHCHD4 overexpression+Liangfang Wenjing Decoction serum group. The protein expression of CHCHD4 and HIF-1α was detected by Western blot, and the glucose consumption and lactic acid level were detected. The cell proliferation was detected by MTT assay. The experiment found that compared with normal rats, the modeling rats showed symptoms of cold coagulation and blood stasis, such as mental malaise, reduced diet and drinking water, disordered estrous cycle, and blocked blood circulation in ears and uterine microvessels. Compared with the sham group, the ectopic lesions in the model group were uplifted, and the mRNA and protein expressions of CHCHD4 and HIF-1α were significantly increased(P<0.05). Compared with the model group, the symptoms of cold coagulation and blood stasis in each treatment group were improved, and the area of ectopic lesions was significantly reduced(P<0.05 or P<0.01). The mRNA and protein expression levels of CHCHD4 and HIF-1α were significantly decreased(P<0.05 or P<0.01). In the cell model, compared with the control group, the expression of CHCHD4, HIF-1α protein, glucose consumption, lactic acid level, and cell proliferation activity in the CHCHD4 overexpression group were significantly increased(P<0.01). Compared with the CHCHD4 overexpression group, there was no significant change in each index in the control serum group, while the protein expression of CHCHD4 and HIF-1α in the Liangfang Wenjing Decoction serum group was decreased significantly(P<0.05 or P<0.01). The glucose consumption, lactic acid level, and cell proliferation activity decreased significantly(P<0.01). It can be seen from the above that the therapeutic effect of Liangfang Wenjing Decoction on EMs with cold coagulation and blood stasis might be related to reducing the expression of CHCHD4 and then improving the hypoxia of ectopic lesions and ectopic ESCs.

[Compatibility mechanism of Qishen Yiqi Dripping Pills for treatment of myocardial ischemia based on UPLC-Q-Exactive Orbitrap-MS and network pharmacology].

Clinical efficacy and mechanism of Qishen Yiqi Dripping Pills(QSYQ) have been well researched, but the compatibility mechanism underlying its therapeutic effect still requires further analysis. This study aims to explore the compatibility mechanism of QSYQ in treating myocardial ischemia. UPLC-Q-Exactive Orbitrap-MS technique was used to obtain the absorbed blood components of QSYQ. Target proteins of the absorbed components were collected and screened using TCMSP, TCMIP, and SwissTargetPrediction databases. Disease proteins related to myocardial ischemia were obtained through GeneCards, OMIM, and DisGeNET databases. Core targets and core components were obtained using online plotting software Venny 2.1.0, STRING, and Cytoscape 3.9.1 software. David database was used for GO functional annotation and KEGG pathway enrichment of core targets, obtaining the main pathways of QSYQ in treating myocardial ischemia and drawing visualized network diagrams. The compatibility mechanism was analyzed based on "component-target", "drug-pathway", and "PI3K-AKT" characteristic pathways, and molecular docking was used for validation. This study obtained 42 absorbed blood components of QSYQ, 556 component targets, 1 980 disease targets, 69 core targets, and 15 core components. QSYQ can exert therapeutic effects on myocardial ischemia by regulating proteins such as MAPK1, RELA, SRC, JUN, and STAT3, acting on signaling pathways such as HIF-1, PI3K-AKT, Toll-like, MAPK, VEGF, etc. The interaction network diagrams of "component-target" and "drug-pathway" preliminarily elucidated the synergy among the four drugs in this prescription at the level of targets and pathways. The PI3K-AKT characteristic pathway indicated that the sovereign drug Huangqi(Astragali Radix) and minister drug Danshen(Salviae Miltiorrhizae Radix et Rhizoma) could regulate most targets in this pathway, while the assistant drug Sanqi(Notoginseng Radix et Rhizoma) cooperated with Huangqi and Danshen on IL6 and AKT proteins, and the envoy drug Jiangxiang(Dalbergiae Odoriferae Lignum) acted on AKT and RXRA proteins, with all drugs acting synergistically on proteins such as AKT, RXRA, NFKB to regulate cell survival and promote angiogenesis. Molecular docking indicated that hydrogen bonding and hydrophobic interactions might be the main forms of action, also validating the distribution of binding energy of the PI3K-AKT signaling pathway. This study analyzed the compatibility connotation of QSYQ from multiple dimensions including drugs, components, targets, and pathways, providing reference basis for the study of the mechanism of action and compatibility rules of QSYQ.

Systemic immunoinflammatory indexes in albuminuric adults are negatively associated with α-klotho: evidence from NHANES 2007-2016.

BACKGROUND: Systemic Immune-Inflammation Index (SII) is a novel inflammatory biomarker closely associated with the inflammatory response and chronic kidney disease. Klotho is implicated as a pathogenic factor in the progression of kidney disease, and supplementation of Klotho may delay the progression of chronic kidney disease by inhibiting the inflammatory response. Our aim is to investigate the potential relationship between SII and Klotho in adult patients in the United States and explore the differences in the populations with and without albuminuria. METHODS: We conducted a cross-sectional study recruiting adult participants with complete data on SII, Klotho, and urine albumin-to-creatinine ratio (ACR) from the National Health and Nutrition Examination Survey from 2007 to 2016. SII was calculated as platelet count × neutrophil count/lymphocyte count, with abnormal elevation defined as values exceeding 330 × 10^9/L. Albuminuria was defined as ACR >30 mg/g. Weighted multivariable regression analysis and subgroup analysis were employed to explore the independent relationship between SII and Klotho. RESULTS: Our study included a total of 10,592 individuals. In all populations, non-albuminuria population, and proteinuria population with ACR ≥ 30, participants with abnormally elevated SII levels, as compared to those with SII less than 330 × 10^9/L, showed a negative correlation between elevated SII levels and increased Klotho, which persisted after adjusting for covariates. CONCLUSIONS: There is a negative correlation between SII and Klotho in adult patients in the United States. This finding complements previous research but requires further analysis through large prospective studies.

Managing tobacco black shank disease using biochar: direct toxicity and indirect ecological mechanisms.

Black shank disease in tobacco, caused by Phytophthora nicotianae, can lead to yield losses of 30%-50% upon outbreak. Recently, biochar derived from agricultural waste has shown significant potential in controlling soil-borne diseases, though its mechanisms remain unclear. Over a 3-year observation period, we found that the incidence of black shank was significantly lower in plots amended with biochar compared with normal cultivation plots. To investigate the underlying mechanisms, we studied both the direct and indirect effects of biochar on black shank. Direct antifungal assays indicated that biochar reduced the total number of sporangia by 53.91%. Further pot experiments revealed a 62.34% reduction in the P. nicotianae population in the soil following biochar application. Additionally, biochar application led to notable changes in soil physicochemical properties and microbial community composition. Microbial species analysis showed that biochar promoted the aggregation of beneficial microbes such as Sphingomonas, Flavisolibacter, and Mucoromycota. Functional predictions using the PICRUSt 2 software revealed that biochar enhances bacterial functions related to antimicrobial substance synthesis (Tetracycline biosynthesis), detoxification metabolism (D-arginine and D-ornithine metabolism, arginine and proline metabolism), and lipid and fatty acid metabolism (Lipopolysaccharide biosynthesis, fatty acid biosynthesis), while fungal functions showed no significant changes. This suggests that rhizosphere bacteria play a more prominent role in the suppression of black shank by biochar, a finding supported by partial least squares path modeling analysis. Therefore, we hypothesize that biochar not only directly inhibits P. nicotianae growth but also regulates the composition of the rhizosphere microbial community, inducing the production of antimicrobial substances by rhizosphere bacteria, effectively preventing P. nicotianae invasion.IMPORTANCEBlack shank, a global soil-borne fungal disease in tobacco, currently lacks effective control methods. Notably, biochar derived from agricultural waste has shown significant potential in controlling soil-borne diseases. Over a 3-year observation period, we found that plots amended with biochar had a significantly lower incidence of black shank compared with normal cultivation plots. However, the mechanisms of disease suppression remained unclear. Through in vitro antifungal assays and pot experiments, we discovered that tobacco-derived biochar can directly inhibit the growth of the pathogen. Additionally, biochar regulates the composition of the rhizosphere microbial community, inducing rhizosphere bacteria to produce antimicrobial substances, effectively preventing pathogen invasion. This discovery reveals both the direct and indirect mechanisms by which biochar suppresses black shank in tobacco. It provides a scientific basis for developing green control technologies for black shank and offers theoretical support for the application of biochar in managing soil-borne diseases in tobacco cultivation areas.

Advances and challenges in serine in the central nervous system: physicochemistry, physiology, and pharmacology.

Neurological disorders are the primary cause of human disability and mortality globally, however, current medications slightly alleviate some symptoms of degenerative diseases. Serine is an important amino acid for the brain function and involved in a variety of biosynthetic pathways and signal transduction processes. The imbalance of serine metabolism is associated with neurodegeneration, including neuroinflammation, oxidative stress and apoptosis. Altered activities of serine metabolizing enzymes and accumulation of serine metabolites affect the survival and function of nerve cells. Abnormal serine levels are observed in animal models with neurological diseases, but not all human studies, therefore, the maintenance of serine homeostasis is a potentially therapeutic strategy for neurological disorders. To date, physiological and pharmacological roles of serine in neurological diseases have not been systemically recapitulated, and the association between serine and neurological diseases is controversial. In this review, we summarize physicochemical properties of serine, biological processes of serine in the brain (source, biotransformation, and transport), and the application of serine in neurological diseases including Alzheimer's disease, schizophrenia, and depression. Here, we highlight physicochemistry, physiology, pharmacology, and therapeutic potentials of serine in the prevention and treatment of neurological dysfunction. Our work provides valuable hints for future investigation that will lead to a comprehensive understanding of serine and its metabolism in cellular physiology and pharmacology. Although broad by necessity, the review helps researchers to understand great potentials of serine in the prevention and treatment of neurological dysfunction.

Hepatic Metabolomic Responses to Low-Temperature Stress in the Invasive Turtle, Trachemys scripta elegans.

Investigating the physiological and biochemical changes of ectothermic species before entering hibernation would contribute to the understanding of how they adapt to low-temperature environments. Here, red-eared slider turtle (Trachemys scripta elegans) hatchlings were maintained under different thermal treatments (24 °C, slowly decreasing temperatures from 24 °C to 14 °C, and to 4 °C). Hepatic metabolite alterations were measured to assess the metabolic impacts of low-temperature stress in this species. Of these differentially changed metabolites, some (e.g., raffinose, spermidine, allocholic acid, taurohyocholate, 2-ketobutyric acid, acetylcysteine) were shown to decrease, while others (e.g., stearolic acid, D-mannose) increased in low-temperature treatments. Our results indicated that short-term low-temperature stress might have limited impacts on lipid and energy metabolism in this species. The changes in other metabolites (e.g., allocholic acid, taurohyocholate, spermine, acetylcysteine) might be associated with a low food intake (and thus reduced digestive performance) and weakened immune ability of low-temperature-exposed animals.

Isolated cassava cells: Comparison of structure and physicochemical properties with starch and whole flour.

Individual cells are the smallest units of the plant tissue structure, and their structure and physicochemical properties are essential for whole food processing. In this study, cassava cells were isolated using acid-alkali, hydrothermal, and pectinase methods, and the differences in microstructure and physicochemical properties among the cells, starch, and whole flour were investigated. Cassava cells isolated using pectinase showed intact individual cells with a higher isolation rate and less damage to the cell wall structure and intracellular composition. The presence of cell walls in intact individual cells inhibited the swelling and leaching of starch, resulting in a lower peak viscosity and higher gelatinization temperature than those of starch. The intact cell structure and non-starch composition enhanced the shear resistance of the gels in the sample. Heat treatment led to the gelatinization of intracellular starch and increased the permeability of the cell wall, destroying the physical barrier function of the cell wall; however, the compact cell matrix and non-starch components can inhibit starch hydrolysis. This study suggests that cells isolated using pectinase can be used to investigate the effect of cell walls on the functional properties of intracellular starch in cassava. The isolated cells provide new insights into the cassava industry.

Lipid synthesis, triggered by PPARγ T166 dephosphorylation, sustains reparative function of macrophages during tissue repair.

Macrophages may acquire a reparative phenotype that supports tissue repair and remodeling in response to tissue injury. However, the metabolic requirements underpinning this process are incompletely understood. Here, we show that posttranslational modification (PTM) of PPARγ regulates lipid synthesis in response to wound microenvironmental cues and that metabolic rewiring orchestrates function of reparative macrophages. In injured tissues, repair signaling leads to decreased macrophage PPARγ threonine 166 (T166) phosphorylation, which results in a partially active PPARγ transcriptional program comprised of increased binding activity to the regulator regions of lipid synthesis-associated genes, thereby increased lipogenesis. The accumulated lipids serve as signaling molecules, triggering STAT3-mediated growth factor expression, and supporting the synthesis of phospholipids for the expansion of the endoplasmic reticulum (ER), which is required for protein secretion. Genetic or pharmacological inhibition of PPARγ T166 phosphorylation promotes the reparative function of macrophages and facilitates tissue regeneration. In summary, our work identifies PPARγ T166-regulated lipid biosynthesis as an essential pathway for meeting the anabolic demands of the activation and function of macrophages and provides a rationale for potential therapeutic targeting of tissue repair.

Ventricular arrhythmias originating from different portions of the communicating vein of the left ventricular summit: electrocardiographic characteristics and catheter ablation.

BACKGROUND: Idiopathic ventricular arrhythmias (IVAs) arising from different portions of the communicating vein of the left ventricular summit (summit-CV) are not a rare phenomenon. Whereas its electrocardiographic (ECG) and electrophysiological characteristics are not fully investigated. OBJECTIVE: This study aimed to identify distinct ECG and electrophysiological features of IVAs originating from different portions of summit-CV. METHODS: Nineteen patients confirmed arising from summit-CV were included in this study. RESULTS: The 19 patients were divided into proximal and distal portion groups based on their target sites in summit-CV. In the proximal portion group, 100% (11/11) VAs showed dominant negative (rs or QS) waves in lead I, while in the distal portion group, 87.5% (7/8) showed dominant positive waves (R, Rs or r) (p < 0.000). In lead V1, 100% (11/11) of the proximal portion group showed dominant positive waves (R or Rs), while 62.50% (5/8) of the distal portion group showed positive and negative bidirectional or negative waves (RS or rS) (p < 0.005). RI>4mV, SI<3.5mV, RV1<13mV, SV1>3.5mV, RI/SI>0.83, and RV1/SV1< 2.6 indicated a distal portion of summit-CV with the predictive value of 0.909, 1.000, 0.653, 0.972, 0.903, 0.966, respectively. A more positive wave in lead I and a more negative wave in lead V1 indicated more distal origin in summit-CV. Target sites in proximal and distal summit-CV groups showed similar electrophysiological characteristics during mapping. CONCLUSIONS: There were significant differences in ECG characteristics of VAs at different portions of summit-CV, which could aid pre-procedure planning and facilitate radiofrequency catheter ablation (RFCA) procedures.

An overview of the direct interaction of synthesized silver nanostructures and enzymes.

Silver nanoparticles (AgNPs) have drawn a lot of attention from a variety of fields, particularly the biological and biomedical sciences. As a result, it is acknowledged that AgNPs' direct interactions with macromolecules such as DNA, proteins, and enzymes are essential for both therapeutic and nanotoxicological applications. Enzymes as important catalysts may interact with AgNP surfaces in a variety of ways. Therefore, mechanistic investigation into the molecular effects of AgNPs on enzyme conformation and function is necessary for a comprehensive assessment of their interactions. In this overview, we aimed to overview the various strategies for producing AgNPs. We then discussed the enzyme activity inhibition (EAI) mechanism by nanostructured particles, followed by an in-depth survey of the interaction of AgNPs with different enzymes. Furthermore, various parameters influencing the interaction of NPs and enzymes, as well as the antibacterial and anticancer effects of AgNPs in the context of the enzyme inhibitors, were discussed. In summary, useful information regarding the biological safety and possible therapeutic applications of AgNPs-enzyme conjugates may be obtained from this review.

Dynamic stress- and inflammatory-based regulation of psychiatric risk loci in human neurons.

The prenatal environment can alter neurodevelopmental and clinical trajectories, markedly increasing risk for psychiatric disorders in childhood and adolescence. To understand if and how fetal exposures to stress and inflammation exacerbate manifestation of genetic risk for complex brain disorders, we report a large-scale context-dependent massively parallel reporter assay (MPRA) in human neurons designed to catalogue genotype x environment (GxE) interactions. Across 240 genome-wide association study (GWAS) loci linked to ten brain traits/disorders, the impact of hydrocortisone, interleukin 6, and interferon alpha on transcriptional activity is empirically evaluated in human induced pluripotent stem cell (hiPSC)-derived glutamatergic neurons. Of ~3,500 candidate regulatory risk elements (CREs), 11% of variants are active at baseline, whereas cue-specific CRE regulatory activity range from a high of 23% (hydrocortisone) to a low of 6% (IL-6). Cue-specific regulatory activity is driven, at least in part, by differences in transcription factor binding activity, the gene targets of which show unique enrichments for brain disorders as well as co-morbid metabolic and immune syndromes. The dynamic nature of genetic regulation informs the influence of environmental factors, reveals a mechanism underlying pleiotropy and variable penetrance, and identifies specific risk variants that confer greater disorder susceptibility after exposure to stress or inflammation. Understanding neurodevelopmental GxE interactions will inform mental health trajectories and uncover novel targets for therapeutic intervention.

Environmentally Relevant Levels of Antiepileptic Carbamazepine Altered Intestinal Microbial Composition and Metabolites in Amphibian Larvae.

There is growing concern about the potential ecological risks posed by pharmaceutical residues in the aquatic environment. However, our understanding of the toxic effects of antiepileptic pharmaceuticals, such as carbamazepine (CBZ), on aquatic animal larvae is still limited. In this study, the tadpoles of the black-spotted pond frog (Pelophylax nigromaculatus) were exposed to environmentally relevant concentrations of CBZ (0.3 and 3.0 µg/L) for 30 days, and their growth, intestinal microbial composition, and metabolites were investigated to assess the potential toxic effects of CBZ in non-targeted aquatic organisms. Some tadpoles died during exposure, but there was no significant among-group difference in the survival and growth rates. CBZ exposure significantly altered the composition of tadpole intestinal microbiota. Relative abundances of some bacterial genera (e.g., Blautia, Prevotella, Bacillus, Microbacterium, etc.) decreased, while others (e.g., Paucibacter, etc.) increased in CBZ-exposed tadpoles. Interestingly, CBZ-induced alterations in some bacteria might not necessarily lead to adverse outcomes for animals. Meanwhile, small molecular intestinal metabolites related to energy metabolism, and antioxidant and anti-inflammatory activities were also altered after exposure. Taken together, environmentally relevant levels of CBZ might alter the metabolic and immune performances of amphibian larvae by modifying the abundance of some specific bacteria and the level of metabolites in their intestines, thereby potentially causing a long-term effect on their fitness.

Isoxerophilusins A and B, Two Novel Polycyclic Asymmetric Diterpene Dimers from Isodon xerophilus: Structural Elucidation, Modification, and Inhibitory Activities against α-Glucosidase.

Isoxerophilusins A (1) and B (2), two unprecedented diterpene heterodimers biogenetically from ent-atisanes and abietanes, were isolated from the rhizomes of Isodon xerophilus. Their structures were determined by extensive spectroscopic analysis and single-crystal X-ray diffraction. Selective esterification of 1 generated 11 new derivatives. All derivatives showed excellent α-glucosidase inhibitory activity in comparison to acarbose. Compounds 12 and 13 demonstrated significant inhibition against α-glucosidase with IC50 values of 4.92 and 3.83 µM, respectively.

ECM1 and ANXA1 in urinary extracellular vesicles serve as biomarkers for breast cancer.

Objective: Although urinary extracellular vesicles (uEVs) have been extensively studied in various cancers, their involvement in breast cancer (BC) remains largely unexplored. The non-invasive nature of urine as a biofluid and its abundant protein content offer considerable potential for the early detection of breast cancer. Methods: This study analyzed the proteomic profiles of uEVs from BC patients and healthy controls (HC). The dysregulation of ECM1 and ANXA1 in the uEVs was validated in a larger cohort of 128 BC patients, 25 HC and 25 benign breast nodules (BBN) by chemiluminescence assay (CLIA). The expression levels of ECM1 and ANXA1 were also confirmed in the uEVs of MMTV-PyMT transgenic breast cancer mouse models. Results: LC-MS/MS analysis identified 571 dysregulated proteins in the uEVs of BC patients. ECM1 and ANXA1 were selected for validation in 128 BC patients, 25 HC and 25 BBN using CLIA, as their fold change showed a significant difference of more than 10 with p-value<0.05. Protein levels of ECM1 and ANXA1 in uEVs were significantly increased in BC patients. In addition, the protein levels of ECM1 and ANXA1 in the uEVs of MMTV-PyMT transgenic mice were observed to increase progressively with the progression of breast cancer. Conclusion: We developed a simple and purification-free assay platform to isolate uEVs and quantitatively detect ECM1 and ANXA1 in uEVs by WGA-coupled magnetic beads and CLIA. Our results suggest that ECM1 and ANXA1 in uEVs could potentially serve as diagnostic biomarkers for breast cancer.