Electrocatalytic Generation of Singlet Oxygen via ROS-Mediated Redox Chain Reaction for Efficient Disinfection.

The risk of harmful microorganisms to ecosystems and human health has stimulated exploration of singlet oxygen (1O2)-based disinfection. It can be potentially generated via an electrocatalytic process, but is limited by the low production yield and unclear intermediate-mediated mechanism. Herein, we designed a two-site catalyst (Fe/Mo-N/C) for the selective 1O2 generation. The Mo sites enhance the generation of 1O2 precursors (H2O2), accompanied by the generation of intermediate •HO2/•O2-. The Fe site facilitates activation of H2O2 into •OH, which accelerates the •HO2/•O2- into 1O2. A possible mechanism for promoting 1O2 production through the ROS-mediated chain reaction is reported. The as-developed electrochemical disinfection system can kill 1 × 107 CFU mL-1 of E. coli within 8 min, leading to cell membrane damage and DNA degradation. It can be effectively applied for the disinfection of medical wastewater. This work provides a general strategy for promoting the production of 1O2 through electrocatalysis and for efficient electrochemical disinfection.

Implications of IFNγ SNP rs2069705 in primary Sjögren's syndrome: transcriptional activation and B cell infiltration.

Primary Sjögren's syndrome (pSS) is characterized by its autoimmune nature. This study investigates the role of the IFNγ SNP rs2069705 in modulating the susceptibility to pSS. Differential expression of IFNγ and BAFF was analyzed using the GEO database's mRNA microarray GSE84844. Genotyping of the IFNγ SNP rs2069705 was conducted via the dbSNP website. The JASPAR tool was used for predicting transcription factor bindings. Techniques such as dual-luciferase reporter assays, Chromatin immunoprecipitation, and analysis of a pSS mouse model were applied to study gene and protein interactions. A notable increase in the mutation frequency of IFNγ SNP rs2069705 was observed in MNCs from the exocrine glands of pSS mouse models. Bioinformatics analysis revealed elevated levels of IFNγ and BAFF in pSS samples. The model exhibited an increase in both CD20+ B cells and cells expressing IFNγ and BAFF. Knocking down IFNγ resulted in lowered BAFF expression and less lymphocyte infiltration, with BAFF overexpression reversing this suppression. Activation of the Janus kinase (JAK)/STAT1 pathway was found to enhance transcription in the BAFF promoter region, highlighting IFNγ's involvement in pSS. In addition, rs2069705 was shown to boost IFNγ transcription by promoting interaction between its promoter and STAT4. SNP rs2069705 in the IFNγ gene emerges as a pivotal element in pSS susceptibility, primarily by augmenting IFNγ transcription, activating the JAK/STAT1 pathway, and leading to B-lymphocyte infiltration in the exocrine glands.NEW & NOTEWORTHY The research employed a combination of bioinformatics analysis, genotyping, and experimental models, providing a multifaceted approach to understanding the complex interactions in pSS. We have uncovered that the rs2069705 SNP significantly affects the transcription of IFNγ, leading to altered immune responses and B-lymphocyte activity in pSS.

Regulation of drought tolerance in Arabidopsis involves the PLATZ4-mediated transcriptional repression of plasma membrane aquaporin PIP2;8.

Plant A/T-rich protein and zinc-binding protein (PLATZ) transcription factors play important roles in plant growth, development and abiotic stress responses. However, how PLATZ influences plant drought tolerance remains poorly understood. The present study showed that PLATZ4 increased drought tolerance in Arabidopsis thaliana by causing stomatal closure. Transcriptional profiling analysis revealed that PLATZ4 affected the expression of a set of genes involved in water and ion transport, antioxidant metabolism, small peptides and abscisic acid (ABA) signaling. Among these genes, the direct binding of PLATZ4 to the A/T-rich sequences in the plasma membrane intrinsic protein 2;8 (PIP2;8) promoter was identified. PIP2;8 consistently reduced drought tolerance in Arabidopsis through inhibiting stomatal closure. PIP2;8 was localized in the plasma membrane, exhibited water channel activity in Xenopus laevis oocytes and acted epistatically to PLATZ4 in regulating the drought stress response in Arabidopsis. PLATZ4 increased ABA sensitivity through upregulating the expression of ABSCISIC ACID INSENSITIVE 3 (ABI3), ABI4 and ABI5. The transcripts of PLATZ4 were induced to high levels in vegetative seedlings under drought and ABA treatments within 6 and 3 h, respectively. Collectively, these findings reveal that PLATZ4 positively influences plant drought tolerance through regulating the expression of PIP2;8 and genes involved in ABA signaling.

Regulation of the mammalian maternal-to-embryonic transition by eukaryotic translation initiation factor 4E.

Eukaryotic translation initiation factor 4E (eIF4E) mediates cap-dependent translation. Genetic and inhibitor studies show that eIF4E expression is required for the successful transition from maternal to embryonic control of mouse embryo development. eIF4E was present in the oocyte and in the cytoplasm soon after fertilization and during each stage of early development. Functional knockout (Eif4e-/-) by PiggyBac [Act-RFP] transposition resulted in peri-implantation embryonic lethality because of the failure of normal epiblast formation. Maternal stores of eIF4E supported development up to the two- to four-cell stage, after which new expression occurred from both maternal and paternal inherited alleles. Inhibition of the maternally acquired stores of eIF4E (using the inhibitor 4EGI-1) resulted in a block at the two-cell stage. eIF4E activity was required for new protein synthesis in the two-cell embryo and Eif4e-/- embryos had lower translational activity compared with wild-type embryos. eIF4E-binding protein 1 (4E-BP1) is a hypophosphorylation-dependent negative regulator of eIF4E. mTOR activity was required for 4E-BP1 phosphorylation and inhibiting mTOR retarded embryo development. Thus, this study shows that eIF4E activity is regulated at key embryonic transitions in the mammalian embryo and is essential for the successful transition from maternal to embryonic control of development.

Ultrafast Unidirectional On-Chip Heat Transfer.

Effective and rapid heat transfer is critical to improving electronic components' performance and operational stability, particularly for highly integrated and miniaturized devices in complex scenarios. However, current thermal manipulation approaches, including the recent advancement in thermal metamaterials, cannot realize fast and unidirectional heat flow control. In addition, any defects in thermal conductive materials cause a significant decrease in thermal conductivity, severely degrading heat transfer performance. Here, the utilization of silicon-based valley photonic crystals (VPCs) is proposed and numerically demonstrated to facilitate ultrafast, unidirectional heat transfer through thermal radiation on a microscale. Utilizing the infrared wavelength region, the approach achieves a significant thermal rectification effect, ensuring continuous heat flow along designed paths with high transmission efficiency. Remarkably, the process is unaffected by temperature gradients due to the unidirectional property, maintaining transmission directionality. Furthermore, the VPCs' inherent robustness affords defect-immune heat transfer, overcoming the limitations of traditional conduction methods that inevitably cause device heating, performance degradation, and energy waste. The design is fully CMOS compatible, thus will find broad applications, particularly for integrated optoelectronic devices.

Controllable Silver Release for Efficient Treatment of Drug-Resistant Bacterial-Infected Wounds.

The use of traditional Ag-based antibacterial agents is usually accompanied by uncontrollable silver release, which makes it difficult to find a balance between antibacterial performance and biosafety. Herein, we prepared a core-shell system of ZIF-8-derived amorphous carbon-coated Ag nanoparticles (Ag@C) as an ideal research model to reveal the synergistic effect and structure-activity relationship of the structural transformation of carbon shell and Ag core on the regulation of silver release behavior. It is found that Ag@C prepared at 600 °C (AC6) exhibits the best ion release kinetics due to the combination of relatively simple shell structure and lower crystallinity of the Ag core, thereby exerting stronger antibacterial properties (>99.999 %) at trace doses (20 µg mL-1) compared with most other Ag-based materials. Meanwhile, the carbon shell prevents the metal Ag from being directly exposed to the organism and thus endows AC6 with excellent biocompatibility. In animal experiments, AC6 can effectively promote wound healing by inactivating drug-resistant bacteria while regulating the expression of TNF-α and CD31. This work provides theoretical support for the scientific design and clinical application of controllable ion-releasing antibacterial agents.

An efficient genetic transformation system mediated by Rhizobium rhizogenes in fruit trees based on the transgenic hairy root to shoot conversion.

Genetic transformation is a critical tool for gene editing and genetic improvement of plants. Although many model plants and crops can be genetically manipulated, genetic transformation systems for fruit trees are either lacking or perform poorly. We used Rhizobium rhizogenes to transfer the target gene into the hairy roots of Malus domestica and Actinidia chinensis. Transgenic roots were generated within 3 weeks, with a transgenic efficiency of 78.8%. Root to shoot conversion of transgenic hairy roots was achieved within 11 weeks, with a regeneration efficiency of 3.3%. Finally, the regulatory genes involved in stem cell activity were used to improve shoot regeneration efficiency. MdWOX5 exhibited the most significant effects, as it led to an improved regeneration efficiency of 20.6% and a reduced regeneration time of 9 weeks. Phenotypes of the overexpression of RUBY system mediated red roots and overexpression of MdRGF5 mediated longer root hairs were observed within 3 weeks, suggesting that the method can be used to quickly screen genes that influence root phenotype scores through root performance, such as root colour, root hair, and lateral root. Obtaining whole plants of the RUBY system and MdRGF5 overexpression lines highlights the convenience of this technology for studying gene functions in whole plants. Overall, we developed an optimized method to improve the transformation efficiency and stability of transformants in fruit trees.

Sex-specific phosphorus acquisition strategies and cycling in dioecious Populus euphratica forests along a natural water availability gradient.

Soil phosphorus (P) availability affects plant growth and distribution. However, it is still unknown how sex-specific variation in functional traits affects plants' P acquisition and soil P transformation. On wet sites, female poplars had a greater specific root length (SRL), and a higher diversity of arbuscular mycorrhizal fungi (AMF) and phosphate-solubilizing bacteria (PSB). Male poplars living on wet sites increased the abundance of AMF and PSB communities and enhanced moderately labile and highly resistant organic P mineralisation via increased phosphatase activity. In contrast, on the dry site, the abundance and diversity of AMF and PSB communities increased in females, enhancing moderately labile and highly resistant organic P mineralisation via elevating phosphatase activities. Males maintained greater SRL and promoted Ca-P mobilisation via the release of root carboxylic acids and rhizosphere acidification on the dry site. The AMF community diversity followed a similar pattern as that of the PSB community when altering the P availability of different-sex plants. Our results indicated that organic P and Ca-P are the major sources of plant-available P in natural P. euphratica forests. Seasonal shifts and geographic locations affected the share of organic and inorganic P pools, and AMF and PSB diversities, ultimately altering sex-specific P acquisition strategies of plants.

Record-High T_{c} and Dome-Shaped Superconductivity in a Medium-Entropy Alloy TaNbHfZr under Pressure up to 160 GPa.

Superconductivity has been one of the focal points in medium and high-entropy alloys (MEAs-HEAs) since the discovery of the body-centered cubic (bcc) HEA superconductor in 2014. Until now, the superconducting transition temperature (T_{c}) of most MEA and HEA superconductors has not exceeded 10 K. Here, we report a TaNbHfZr bulk MEA superconductor crystallized in the BCC structure with a T_{c} of 15.3 K which set a new record. During compression, T_{c} follows a dome-shaped curve. It reaches a broad maximum of roughly 15 K at around 70 GPa before decreasing to 9.3 K at 157.2 GPa. First-principles calculations attribute the dome-shaped curve to two competing effects, that is, the enhancement of the logarithmically averaged characteristic phonon frequency ω_{log} and the simultaneous suppression of the electron-phonon coupling constant λ. Thus, TaNbHfZr MEA may have a promising future for studying the underlying quantum physics, as well as developing new applications under extreme conditions.

Serum Fatty Acid Profiles and Neurofilament Light Chain Levels in the General Population.

BACKGROUND: Previous studies have demonstrated associations between fatty acids and neurological disorders. However, no studies have examined the relationship between serum fatty acid levels and serum neurofilament light chain (NfL), a biomarker of neurological disorders. OBJECTIVE: This study aimed to comprehensively investigate the intricate relationship between 30 serum fatty acids and serum NfL levels in a nationally representative sample of U.S. adults, utilizing data from the 2013-2014 National Health and Nutrition Examination Survey. METHODS: Employing a cross-sectional analysis, multivariable linear regression models were utilized to explore the associations between 30 serum fatty acids and serum NfL levels. This analysis involved adjustment for potential confounding variables, including age, sex, race, body-mass index (BMI), smoking status, hyperlipidemia, and diabetes, to clarify the association between serum fatty acids and serum NfL levels. RESULTS: The analysis revealed that certain fatty acids exhibited distinct associations with serum NfL levels. Notably, Docosanoic acid (22:0) and Tricosanoic acid (C23:0) were found to be inversely associated with serum NfL levels (ß = -0.280, 95% CI: -0.525, -0.035; ß = -0.292, 95% CI: -0.511, -0.072). Conversely, Palmitoleic acid (16:1n-7) demonstrated a positive association with serum NfL levels (ß = 0.125, 95% CI: 0.027, 0.222). Notably, these associations remained significant even after adjustment for potential confounders. CONCLUSIONS: Individuals with high relative concentrations of certain saturated fatty acids exhibited decreased serum NfL, whereas those with high relative concentrations of certain monounsaturated fatty acids showed increased serum NfL. These findings contribute to a deeper understanding of the potential impact of serum fatty acids on NfL levels, shedding light on novel avenues for further investigation and potential interventions in the context of neurological health.

Examining the paradox: increased malaria risk in children under 5 in female-headed households in Nigeria.

BACKGROUND: Nigeria is facing a severe malaria crisis, accounting for a significant proportion of global cases and deaths of malaria. This study aimed to investigate the differences between female-headed households (FHHs) and male-headed households (MHHs) and their impact on malaria risk among children under five (U5) in Nigeria. METHODS: Data from the 2021 Nigeria Malaria Indicator Survey (NMIS) were used for this cross-sectional study. A representative sample of 10,988 households was analysed, with key variables subjected to frequency calculations, descriptive statistics, and bivariate analyses using t-tests and chi-square analyses to compare the differences between FHHs and MHHs. RESULTS: Among all participants, 92.1% (N = 10,126) reported residing in male-headed households, while 7.8% (N = 862) reported living in female-headed households. MHHs were significantly more likely to own insecticide-treated bed nets (ITNs) than FHHs (64.7% vs. 53.6%, P < 0.001). U5 children in MHHs had a greater likelihood of sleeping under a bed net the night before the survey than U5 children in FHHs (35.3% vs. 30.0%, P < 0.05). The prevalence of fever in the previous two weeks among U5 children was similar in MHHs and FHHs (35.4% vs. 31.4%), and the testing rates for malaria among U5 children who experienced febrile episodes were higher in MHHs than FHHs (22.4% vs. 15.4%, P < 0.05). Although not statistically significant, FHHs exhibited a higher percentage of U5 children testing positive for malaria compared to MHHs (87.8% vs. 78.9%). On the other hand, FHHs had higher education levels, overall wealth index scores, and a larger presence in urban areas compared to MHHs (P < 0.001). Moreover, FHHs reported higher adherence to malaria prevention awareness (P < 0.001). CONCLUSION: In Nigeria, FHHs enjoy relatively better socioeconomic conditions and stronger awareness of malaria prevention compared to their male-headed counterparts. Contrary to expectations, FHHs are at an increased risk of malaria in children under 5 years old. This phenomenon is associated with entrenched gender inequality and the challenges women face in accessing critical assets. As women in FHHs bear the responsibility of income generation while caring for their children, it is crucial to prioritize interventions that address malaria management in FHHs to reduce both malaria incidence and mortality rates.

Imbalance of T follicular helper cell subsets trigger the differentiation of pathogenic B cells in idiopathic membranous nephropathy.

OBJECTIVE: This study aims to elucidate the role of T follicular helper (Tfh) cells and their subsets in idiopathic membranous nephropathy (IMN). METHODS: The frequencies of Tfh cell subsets and B cell subsets in peripheral blood (PB) were detected in both IMN patients and healthy controls (HCs). The involvement of Tfh cells in the disease pathogenesis was examined by coculturing human Tfh cells with B cells. The dynamic changes of Tfh cells in PB or spleen were monitored in passive Heymann nephritis (PHN) rats. RESULTS: The frequencies of circulating Tfh (cTfh) cells, cTfh2 cells, and plasmablasts were enriched in the PB of patients with IMN. cTfh cells expressed higher ICOS, and lower BTLA than healthy counterparts. The frequency of ICOS + cTfh2 was associated with the severity of IMN, including 24h urine protein, IgG4 concentration and the IgG4: IgG ratio. Positive correlations were also observed between the frequency of cTfh2 cells with plasmablasts, serum IL-21 and IL-4 levels. Importantly, cTfh cells isolated from IMN patients were able to induce the differentiation of B cells to memory B cells (MBC) and plasmablasts, this process could be substantially attenuated by blocking the IL-21. Similar increases of ICOS + cTfh cells were also detected in spleen of PHN rats, concomitant with elevated urine protein levels. CONCLUSIONS: Collectively, our results demonstrate that the imbalance of cTfh cell subsets play a crucial pathogenic role in IMN by inducing the differentiation of B cells through IL-21, and cTfh2 cells might serve as useful markers to evaluate the progression of IMN.

EXPAR for biosensing: recent developments and applications.

Emerging as a promising novel amplification technique, the exponential amplification reaction (EXPAR) offers significant advantages due to its potent exponential amplification capability, straightforward reaction design, rapid reaction kinetics, and isothermal operation. The past few years have witnessed swift advancements and refinements in EXPAR-based technologies, with numerous high-performance biosensing systems documented. A deeper understanding of the EXPAR mechanism has facilitated the proposal of novel strategies to overcome limitations inherent to traditional EXPAR. Furthermore, the synergistic integration of EXPAR with diverse amplification methodologies, including the use of a CRISPR/Cas system, metal nanoparticles, aptamers, alternative isothermal amplification techniques, and enzymes, has significantly bolstered analytical efficacy, aiming to enhance specificity, sensitivity, and amplification efficiency. This comprehensive review presents a detailed exposition of the EXPAR mechanism and analyzes its primary challenges. Additionally, we summarize the latest research advancements in the biomedical field concerning the integration of EXPAR with diverse amplification technologies for sensing strategies. Finally, we discuss the challenges and future prospects of EXPAR technology in the realms of biosensing and clinical applications.

Metal-free iodination of arylaldehydes for total synthesis of aristogins A-F and hernandial.

Iodine is one of the most effective sources for iodination of aromatic compounds; however, its electrophilicity is insufficient for direct iodination. The selection of appropriate environmentally friendly and cost-effective oxidants in combination with iodine for the iodination of aromatic rings, along with its application in the synthesis of natural products, holds significant importance. A highly efficient method utilizing I(III) as the initiator has been successfully developed for monoiodination of arylaldehydes. The method demonstrates good compatibility with a wide range of (hetero)aromatic aldehydes, resulting in moderate to excellent yields, without the need for any toxic, volatile or explosive reagents. The synthesis of seven natural products, namely aristogins A-F and hernandial, was achieved through this iodination followed by Ullmann-type coupling.

C/EBPß isoform-specific regulation of podocyte pyroptosis in lupus nephritis-induced renal injury.

As an essential factor in the prognosis of systemic lupus erythematosus (SLE), lupus nephritis (LN) can accelerate the rate at which patients with SLE can transition to chronic kidney disease or even end-stage renal disease. Podocytes now appear to be a possible direct target in LN in addition to being prone to collateral damage from glomerular capillary lesions induces by immune complexes and inflammatory processes. The NLRP3 inflammasome is regulated by CCAAT/enhancer-binding protein ß (C/EBPß), which is involved in the pathogenesis of SLE. However, the role and mechanism of C/EBPß in LN remain unclear. In this investigation, glomerular podocytes treated with LN serum and MRL/lpr mice were employed as in vivo and in vitro models of LN, respectively. In vivo, the expression of C/EBPß isoforms was detected in kidney specimens of humans and mice with LN. Then we assessed the effect of C/EBPß inhibition on renal structure and function by injecting RNAi adeno-associated virus of C/EBPß shRNA into MRL/lpr mice. In vitro, glomerular podocytes were treated with LN serum and C/EBPß siRNA to explore the role of C/EBPß in the activation of the AIM2 inflammasome and podocyte injury. C/EBPß-LAP and C/EBPß-LIP were significantly overexpressed in kidney tissue samples from LN patients and mice, and C/EBPß inhibition significantly alleviated renal function damage and ameliorated renal structural deficiencies. Inflammatory pathways downstream from the AIM2 inflammasome could be suppressed by C/EBPß knockdown. Furthermore, the upregulation of C/EBPß-LAP could activate the AIM2 inflammasome and podocyte pyroptosis by binding to the promoters of AIM2 and CASPASE1 to enhance their expression, and the knockdown of AIM2 or (and) caspase-1 reversed the effects of C/EBPß-LAP overexpression. Interestingly, C/EBPß-LIP overexpression could transcriptionally inhibit IRAG and promote Ca2+ release-mediated activation of the AIM2 inflammasome. This finding suggests that C/EBPß is not only involved in the regulation of the expression of key proteins of the AIM2 inflammasome but also affects the polymerization of key proteins of the AIM2 inflammasome through the regulation of Ca2+ release. In conclusion, this study provides a new idea for studying the regulatory mechanism of C/EBPß and provides a theoretical basis for the early diagnosis and treatment of LN in the future. © 2023 The Pathological Society of Great Britain and Ireland.

Cohort profile: Beijing Healthy Aging Cohort Study (BHACS).

The Beijing Healthy Aging Cohort Study (BHACS) was established to supplement the limited data of a large representative cohort of older people based on the general population and was designed to evaluate the prevalence, incidence, and natural history of cognitive decline, functional disability, and conventional vascular risk factors. The aim was to determine the evolution of these conditions by estimating the rates and determinants of progression and regression to adverse outcomes, including dementia, cardiovascular events, cancer, and all-cause death. It can therefore provide evidence to help policy makers develop better policies to promote healthy aging in China. BHACS consisted of three cohorts (BLSA, CCHS-Beijing, and BECHCS) in Beijing with a total population of 11 235 (6281 in urban and 4954 in rural areas) and an age range of 55 years or older (55-101 years) with a mean age of 70.35 ± 7.71 years (70.69 ± 7.62 years in urban and 69.92 ± 7.80 years in rural areas). BHACS-BLSA conducted the baseline survey in 2009 with a multistage stratification-random clustering procedure for people aged 55 years or older; BHACS-CCHS-Beijing conducted the baseline survey in 2013-2015 with a stratified multistage cluster random sampling method for people aged 55 years or older; and BHACS-BECHCS conducted the baseline survey in 2010-2014 with two-stage cluster random sampling method for people aged 60 years or older. Data were collected through questionnaires, physical measurements, and laboratory analyses. Topics covered by BHACS include a wide range of physical and mental health indicators, lifestyles and personal, family, and socio-economic determinants of health. There are no immediate plans to make the cohort data freely available to the public, but specific proposals for further collaboration are welcome. For further information and collaboration, please contact the corresponding author Yao He (e-mail: yhe301@x263.net).

Chitosan-sodium alginate-polyethylene glycol-Ally isothiocyante nanocomposites ameliorates isoproterenol-induced myocardial infarction in rats.

Myocardial infarction (MI) is a common type of ischemic heart disease that affects millions of people worldwide. In recent times, nanotechnology has become a very promising field with immense applications. The current exploration was conducted to synthesize the chitosan-sodium alginate-polyethylene glycol-Ally isothiocyanate nanocomposites (CSP-AIso-NCs) and evaluate their beneficial roles against the isoproterenol (ISO)-induced MI in rats. The CSP-AIso-NCs were prepared and characterized by several characterization techniques. The MI was initiated in the rats by the administration of 85 mg/kg of ISO for 2 days and treated with 10 and 20 mg/kg of CSP-AIso-NCs for 1 month. The changes in heart weight and bodyweight were measured. The cardiac function markers were assessed with echocardiography. The lipid profiles, Na+, K+, and Ca2+ ions, cardiac biomarkers, antioxidant parameters, and inflammatory cytokines were assessed using corresponding assay kits. The histopathological study was done on the heart tissues. The UV spectral analysis revealed the maximum peak at 208 nm, which confirms the formation of CSP-AIso-NCs. The FT-IR analysis revealed the occurrence of different functional groups, and the crystallinity of the CSP-AIso-NCs was proved by the XRD analysis. DLS analysis indicated the size of the CSP-AIso-NCs at 146.50 nm. The CSP-AIso-NCs treatment increased the bodyweight and decreased the HW/BW ratio in the MI rats. The status of lipids was reduced, and HDL was elevated in the CSP-AIso-NCs administered to MI rats. CSP-AIso-NCs decreased the LVEDs, LVEDd, and NT-proBNP and increased the LVEF level. The oxidative stress markers were decreased, and the antioxidants were increased by the CSP-AIso-NCs treatment in the MI rats. The Na+ and Ca+ ions were reduced, and the K+ ions were increased by the CSP-AIso-NCs. The interleukin-1ß and tumor necrosis factor-α were also depleted, and Nrf-2 was improved in the CSP-AIso-NCs administered to MI rats. The histological study revealed the ameliorative effects of CSP-AIso-NCs. Overall, our outcomes revealed that the CSP-AIso-NCs are effective against the ISO-induced MI rats. Hence, it could be a hopeful therapeutic nanomedicine for MI treatment.

Lumbar foraminal stenosis was associated with back pain and leg pain: epidemiological evidence from a population-based cohort.

OBJECTIVES: To determine the characteristics of lumbar foraminal stenosis (LFS) on magnetic resonance (MR) images and their association with back pain and radiating leg pain in a population-based sample of Chinese subjects. METHODS: This study was an extension of the Hangzhou Lumbar Spine Study, a cross-sectional study focusing on back pain and lumbar spine MR imaging findings. Questionnaire data, including demographics, lifestyle, occupational exposures, back pain and radiating leg pain were included. On lumbar spine MR images, disc degeneration was assessed using Pfirrmann grade and Modic changes were evaluated. Using Lee's scale, the L3-S1 intervertebral foramina were evaluated, with grade 2-3 representing substantial LFS and grade 0-1 no LFS. Characteristics of LFS were noted, and associations of LFS with back pain and radiating leg pain were examined. RESULTS: Among the 644 study subjects, 141 (21.9%) had at least one LFS, and its occurrence was associated with greater age (OR = 1.93 for each 10 years, p < 0.001). Substantial LFS was associated with the presence of back pain (OR = 1.92, p = 0.001) and the intensity of the worst back pain (Coef = 8.30, p < 0.001) over the past 12 months, and disabling back pain during their lifetime (OR = 2.25, p < 0.001). Substantial LFS was also associated with leg pain (OR = 14.27, p < 0.001), with a sensitivity of 75.7% for the presence of radiating leg pain and a specificity of 81.4%. CONCLUSION: Substantial LFS on MR images was a common age-related degenerative phenotype in adults, and appears to be an independent risk factor for back pain and leg pain.

Putative causal relations among gut flora, serums metabolites and arrhythmia: a Mendelian randomization study.

BACKGROUND: The pathogenesis of cardiac arrhythmias is multifaceted, encompassing genetic, environmental, hemodynamic, and various causative factors. Emerging evidence underscores a plausible connection between gut flora, serum metabolites, and specific types of arrhythmias. Recognizing the role of host genetics in shaping the microbiota, we employed two-sample Mendelian randomization analyses to investigate potential causal associations between gut flora, serum metabolites, and distinct arrhythmias. METHODS: Mendelian randomization methods were deployed to ascertain causal relationships between 211 gut flora, 575 serum metabolites, and various types of arrhythmias. To ensure the reliability of the findings, five complementary Mendelian randomization methods, including inverse variance weighting methods, were employed. The robustness of the results was scrutinized through a battery of sensitivity analyses, incorporating the Cochran Q test, leave-one-out test, and MR-Egger intercept analysis. RESULTS: Eighteen gut flora and twenty-six serum metabolites demonstrated associations with the risk of developing atrial fibrillation. Moreover, ten gut flora and fifty-two serum metabolites were linked to the risk of developing supraventricular tachycardia, while eight gut flora and twenty-five serum metabolites were associated with the risk of developing tachycardia. Additionally, six gut flora and twenty-one serum metabolites exhibited associations with the risk of developing bradycardia. CONCLUSION: This study revealed the potential causal relationship that may exist between gut flora, serum metabolites and different cardiac arrhythmias and highlights the need for further exploration. This study provides new perspectives to enhance diagnostic and therapeutic strategies in the field of cardiac arrhythmias.

Physical activity modified association of urinary metals mixture and fasting blood glucose in children: From two panel studies.

There is unclear evidence available on the associations between multiple metals and fasting blood glucose (FBG) in children, and whether they could be beneficial from physical activity. We included 283 children aged 4-12 years from two panel studies with 4-consecutive morning urinary 13 essential metals and 10 non-essential metals repeated across 3 seasons. We employed multiple informant model, linear mixed-effect model, and quantile g-computation to evaluate associations of single metal and their mixture with FBG and interactions with extra-school activity. The results showed that positive relations of multiple essential metals (aluminum, chromium, copper, iron, molybdenum (Mo), nickel, selenium (Se), strontium, zinc) and non-essential metals (arsenic (As), cadmium (Cd), rubidium, titanium (Ti), thallium) with FBG were the strongest at lag 0 (the health examination day), especially in overweight & obesity children (FDR <0.05). The strongest effect presented 1-fold increment in As was related to FBG increased 1.66% (95%CI: 0.84%, 2.48%) in overweight & obesity children. Notably, modification of extra-school activity showed significant, and the effects of multiple metals on FBG were attenuated in children taking total extra-school activity ≥1 h/day, and only one type of which, low or moderate & high intensity extra-school activity reached 20 min/day (Pint <0.05). For instance, each 1-fold increased As was associated with 1.41% increased FBG in overall children taking total extra-school activity <1 h/day, while that of 0.13% in those ≥1 h/day. Meanwhile, mixture of all, essential and non-essential metals were associated with increased FBG, a trend that decreased and became nonsignificant in children having certain extra-school activity, which were dominated by Mo, Se, Ti, Cd. And such relations were substantially beneficial from extra-school activity in overweight & obesity children. Accordingly, multiple essential and non-essential metals, both individual and in mixture, were positively related to FBG in children, which might be attenuated by regular physical activity.