Deciphering the Catalytic Mechanism of Peroxidase-like Activity of Iron Sulfide Nanozymes.

Iron sulfide nanomaterials represented by FeS2 and Fe3S4 nanozymes have attracted increasing attention due to their biocompatibility and peroxidase-like (POD-like) catalytic activity in disease diagnosis and treatments. However, the mechanism responsible for their POD-like activities remains unclear. Herein, taking the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) by H2O2 on FeS2(100) and Fe3S4(001) surfaces, the catalytic mechanism was investigated in detail using density functional theory (DFT) calculations and experimental characterizations. Our experimental results showed that the catalytic activity of FeS2 nanozymes was significantly higher than that of Fe3S4 nanozymes. Our DFT calculations indicated that the surface iron ions of iron sulfide nanozymes could effectively catalyze the production of HO• radicals via the interactions between Fe 3d electrons and the frontier orbitals of H2O2 in the range of -10 to 5 eV. However, FeS2 nanozymes exhibited higher POD-like activity due to the surface Fe(II) binding to H2O2, forming inner-orbital complexes, which results in a larger binding energy and a smaller energy barrier for the base-like decomposition of H2O2. In contrast, the surface iron ions of Fe3S4 nanozymes bind to H2O2, forming outer-orbital complexes, which results in a smaller binding energy and a larger energy barrier for the base-like decomposition of H2O2. The charge transfer analysis showed that FeS2 nanozymes transferred 0.12 e and Fe3S4 nanozymes transferred 0.05 e from their surface iron ions to H2O2, respectively. The simulations were consistent with the experimental observations that the FeS2 nanozymes had a greater affinity for H2O2 compared to that of Fe3S4 nanozymes. This work provides a theoretical foundation for the rational design and accurate preparation of iron sulfide functional nanozymes.

Association Between Added Sugar Intake and Urinary Incontinence in Females: A Cross-sectional Population-based Study.

INTRODUCTION AND HYPOTHESIS: Urinary incontinence (UI) is a widespread issue in women that severely impacts quality of life. The addition of sugar is associated with multiple adverse effects on health. This study examined the potential association between added sugar intake and UI. METHODS: Adult females from the National Health and Nutrition Examination Survey database (2005-2018) were included in this study. The primary outcomes were the prevalence of stress urinary incontinence (SUI), urge urinary incontinence (UUI), and mixed urinary incontinence (MUI). Weighted logistic regression, stratified logistic regression, restricted cubic spline regression, and sensitivity analyses were utilized to determine whether added sugar was associated with UI after multivariate adjustment. RESULTS: A total of 14,927 participants met the inclusion criteria. The results revealed a heightened prevalence of SUI, UUI, and MUI in the fourth quartile of added sugar energy percentage (OR = 1.304, 95% confidence interval [CI] = 1.105-1.539; OR = 1.464, 95% CI = 1.248-1.717; OR = 1.657, 95% CI = 1.329-2.065 respectively). The effect was more pronounced in young women and the subgroup analyses did not reveal any noteworthy interaction effects. According to the sensitivity analyses, the results for SUI and the MUI were consistent with those of the primary analyses. CONCLUSIONS: The excessive intake of added sugar among women may increase their risk of SUI and MUI. Our study highlights the negative effects of added sugar on female genitourinary health and highlights the need for universal access to healthy diets.

The m7G Methyltransferase Mettl1 Drives Cardiac Hypertrophy by Regulating SRSF9-Mediated Splicing of NFATc4.

Cardiac hypertrophy is a key factor driving heart failure (HF), yet its pathogenesis remains incompletely elucidated. Mettl1-catalyzed RNA N7-methylguanosine (m7G) modification has been implicated in ischemic cardiac injury and fibrosis. This study aims to elucidate the role of Mettl1 and the mechanism underlying non-ischemic cardiac hypertrophy and HF. It is found that Mettl1 is upregulated in human failing hearts and hypertrophic murine hearts following transverse aortic constriction (TAC) and Angiotensin II (Ang II) infusion. YY1 acts as a transcriptional factor for Mettl1 during cardiac hypertrophy. Mettl1 knockout alleviates cardiac hypertrophy and dysfunction upon pressure overload from TAC or Ang II stimulation. Conversely, cardiac-specific overexpression of Mettl1 results in cardiac remodeling. Mechanically, Mettl1 increases SRSF9 expression by inducing m7G modification of SRSF9 mRNA, facilitating alternative splicing and stabilization of NFATc4, thereby promoting cardiac hypertrophy. Moreover, the knockdown of SRSF9 protects against TAC- or Mettl1-induced cardiac hypertrophic phenotypes in vivo and in vitro. The study identifies Mettl1 as a crucial regulator of cardiac hypertrophy, providing a novel therapeutic target for HF.

Clock-dependent chromatin accessibility rhythms regulate circadian transcription.

Chromatin organization plays a crucial role in gene regulation by controlling the accessibility of DNA to transcription machinery. While significant progress has been made in understanding the regulatory role of clock proteins in circadian rhythms, how chromatin organization affects circadian rhythms remains poorly understood. Here, we employed ATAC-seq (Assay for Transposase-Accessible Chromatin with Sequencing) on FAC-sorted Drosophila clock neurons to assess genome-wide chromatin accessibility at dawn and dusk over the circadian cycle. We observed significant oscillations in chromatin accessibility at promoter and enhancer regions of hundreds of genes, with enhanced accessibility either at dusk or dawn, which correlated with their peak transcriptional activity. Notably, genes with enhanced accessibility at dusk were enriched with E-box motifs, while those more accessible at dawn were enriched with VRI/PDP1-box motifs, indicating that they are regulated by the core circadian feedback loops, PER/CLK and VRI/PDP1, respectively. Further, we observed a complete loss of chromatin accessibility rhythms in per01 null mutants, with chromatin consistently accessible at both dawn and dusk, underscoring the critical role of Period protein in driving chromatin compaction during the repression phase at dawn. Together, this study demonstrates the significant role of chromatin organization in circadian regulation, revealing how the interplay between clock proteins and chromatin structure orchestrates the precise timing of biological processes throughout the day. This work further implies that variations in chromatin accessibility might play a central role in the generation of diverse circadian gene expression patterns in clock neurons.

Inferring upstream regulatory genes of FOXP3 in human regulatory T cells from time-series transcriptomic data.

The discovery of upstream regulatory genes of a gene of interest still remains challenging. Here we applied a scalable computational method to unbiasedly predict candidate regulatory genes of critical transcription factors by searching the whole genome. We illustrated our approach with a case study on the master regulator FOXP3 of human primary regulatory T cells (Tregs). While target genes of FOXP3 have been identified, its upstream regulatory machinery still remains elusive. Our methodology selected five top-ranked candidates that were tested via proof-of-concept experiments. Following knockdown, three out of five candidates showed significant effects on the mRNA expression of FOXP3 across multiple donors. This provides insights into the regulatory mechanisms modulating FOXP3 transcriptional expression in Tregs. Overall, at the genome level this represents a high level of accuracy in predicting upstream regulatory genes of key genes of interest.

Genetically determined gut microbiota associates with pulmonary arterial hypertension: a Mendelian randomization study.

BACKGROUND: Emerging evidences have demonstrated that gut microbiota composition is associated with pulmonary arterial hypertension (PAH). However, the underlying causality between intestinal dysbiosis and PAH remains unresolved. METHOD: An analysis using the two-sample Mendelian randomization (MR) approach was conducted to examine the potential causal relationship between gut microbiota and PAH. To assess exposure data, genetic variants associated with 196 bacterial traits were extracted from the MiBioGen consortium, which included a sample size of 18,340 individuals. As for the outcomes, summary statistics for PAH were obtained from the NHGRI-EBI GWAS Catalog, which conducted a meta-analysis of four independent studies comprising a total of 11,744 samples. Causal effects were estimated employing various methods, including inverse variance weighted (IVW), MR-Egger, weighted median, weight mode and simple mode, with sensitivity analyses also being implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots. RESULTS: Following false discovery rate (FDR) correction, the genetically predicted genus Eubacterium fissicatena group (odds ratio (OR) 1.471, 95% confidence interval (CI) 1.178-1.837, q = 0.076) exhibited a causal association with PAH. In addition, the genus LachnospiraceaeUCG004 (OR 1.511, 95% CI 1.048-2.177) and genus RuminococcaceaeUCG002 (OR 1.407, 95% CI 1.040-1.905) showed a suggestive increased risk of PAH, while genus Eubacterium eligens group (OR 0.563, 95% CI 0.344-0.922), genus Phascolarctobacterium (OR 0.692, 95% CI 0.487-0.982), genus Erysipelatoclostridium (OR 0.757, 95% CI 0.579-0.989) and genus T-yzzerella3 (OR 0.768, 95% CI 0.624-0.945) were found to have nominal protective effect against PAH. CONCLUSION: The findings from our MR study have revealed a potential causal relationship between gut microbiota and PAH. Specifically, we have identified four types of gut microbiota that exhibit a protective effect on PAH, as well as three types that have a detrimental impact on PAH, thereby offering valuable insights for future mechanistic and clinical investigations in the field of PAH.

From creep to flow: Granular materials under cyclic shear.

When unperturbed, granular materials form stable structures that resemble the ones of other amorphous solids like metallic or colloidal glasses. Whether or not granular materials under shear have an elastic response is not known, and also the influence of particle surface roughness on the yielding transition has so far remained elusive. Here we use X-ray tomography to determine the three-dimensional microscopic dynamics of two granular systems that have different roughness and that are driven by cyclic shear. Both systems, and for all shear amplitudes Γ considered, show a cross-over from creep to diffusive dynamics, indicating that rough granular materials have no elastic response and always yield, in stark contrast to simple glasses. For the system with small roughness, we observe a clear dynamic change at Γ ≈ 0.1, accompanied by a pronounced slowing down and dynamical heterogeneity. For the large roughness system, the dynamics evolves instead continuously as a function of Γ. We rationalize this roughness dependence using the potential energy landscape of the systems: The roughness induces to this landscape a micro-corrugation with a new length scale, whose ratio over the particle size is the relevant parameter. Our results reveal the unexpected richness in relaxation mechanisms for real granular materials.

Single-Step Control of Liquid-Liquid Crystalline Phase Separation by Depletion Gradients.

Fine-tuning nucleation and growth of colloidal liquid crystalline (LC) droplets, also known as tactoids, is highly desirable in both fundamental science and technological applications. However, the tactoid structure results from the trade-off between thermodynamics and nonequilibrium kinetics effects, and controlling liquid-liquid crystalline phase separation (LLCPS) in these systems is still a work in progress. Here, a single-step strategy is introduced to obtain a rich palette of morphologies for tactoids formed via nucleation and growth within an initially isotropic phase exposed to a gradient of depletants. The simultaneous appearance is shown of rich LC structures along the depleting potential gradient, where the position of each LC structure is correlated with the magnitude of the depleting potential. Changing the size (nanoparticles) or the nature (polymers) of the depleting agent provides additional, precise control over the resulting LC structures through a size-selective mechanism, where the depletant may be found both within and outside the LC droplets. The use of depletion gradients from depletants of varying sizes and nature offers a powerful toolbox for manipulation, templating, imaging, and understanding heterogeneous colloidal LC structures.

Environment-induced heritable variations are common in Arabidopsis thaliana.

Parental or ancestral environments can induce heritable phenotypic changes, but whether such environment-induced heritable changes are a common phenomenon remains unexplored. Here, we subject 14 genotypes of Arabidopsis thaliana to 10 different environmental treatments and observe phenotypic and genome-wide gene expression changes over four successive generations. We find that all treatments caused heritable phenotypic and gene expression changes, with a substantial proportion stably transmitted over all observed generations. Intriguingly, the susceptibility of a genotype to environmental inductions could be predicted based on the transposon abundance in the genome. Our study thus challenges the classic view that the environment only participates in the selection of heritable variation and suggests that the environment can play a significant role in generating of heritable variations.

Palladium-Catalyzed Domino Heck/Cross-Coupling Cyclization Reaction: Diastereoselective Synthesis of Furan-Containing Indolines.

Herein, a palladium-catalyzed diastereoselective dearomatization/cross-coupling cyclization reaction between N-arylacyl indoles and (E)-ß-chlorovinyl ketones is reported. Through this cyclization/cycloisomerization cascade, a series of furan-containing indolines were obtained in yields up to 95%. The reaction features readily accessible starting materials, benzyl Pd(II)-catalyzed cycloisomerization of (E)-ß-chlorovinyl ketones, the sequential formation of three bonds and bis-heterocycles, and excellent diastereoselectivity. More importantly, the carbene-secondary benzyl migratory insertion is proven to be a critical process in the sequential cyclizations.

Risk of intracranial hemorrhage in patients using anticoagulant therapy for atrial fibrillation after cerebral microbleeds combined with acute ischemic stroke: a meta-analysis.

Objective: To evaluate intracerebral hemorrhage (ICH) risk in patients with ischemic stroke (IS) and cerebral microbleeds (CMBs) undergoing anticoagulation therapy for non-valvular atrial fibrillation (AF). Methods: We conducted a comprehensive search across multiple databases, including Embase, PubMed, Cochrane, UpToDate, Scopus, WOS, and SinoMed. The search covered observational literature published from each database inception until February 1, 2023. We analyzed the prevalence of CMBs during the follow-up period, compared future ICH risk between patients with and without baseline CMBs (CMBs presence/absence, ≧5 CMBs), and examined factors influencing ICH occurrence in patients with CMBs. Also studied recurrent stroke during anticoagulation therapy, the risk of future ICH when white matter hyperintensity (WMH) and CMBs coexist, and the effects of anticoagulants vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) on future ICH. Results: We included 7 articles involving 5,134 participants. The incidence of CMBs was 24%; baseline CMBs were associated with an increased ICH risk compared to patients without CMBs. ICH-risk was more significant in patients with baseline ≥5 CMBs. After anticoagulant therapy, ICH risk was higher than that of recurrent IS. The risk of future ICH was significantly increased with anticoagulant VKAs compared with NOAC. Conclusion: Anticoagulant therapy for ischemic stroke patients with non-valvular AF and CMBs increases future ICH risk. Discontinuing anticoagulation due to ICH risk should be avoided. NOACs are safe and effective for patients with CMBs and IS.

Simulation research on aerodynamic noise characteristics of a compressor under different working conditions.

The shear stress transport turbulence model is employed to conduct a detailed study of flow characteristics at the highest efficiency point and near-stall point in a full-channel 1.5-stage compressor in this paper. The simulation results for the compressor's total pressure ratio and efficiency exhibit good agreement with experimental data. Emphasis is placed on examining the internal flow structure in the tip area of the compressor rotor under near-stall conditions. The results reveal that significant differences in flow structure primarily occur in the tip area as the compressor approaches stall. Specifically, a reduction in turbulent kinetic energy is observed in a region spanning approximately 20%-60% of the chord length on the rotor suction face near-stall conditions. Two additional peak frequencies, at 0.8 and 1.6 times the blade passage frequency, are observed, and the intricate flow phenomena are elaborated at the near-stall point. The near-stall point exhibits greater noise levels than the highest efficiency point, where the intensity of the surface source increases by more than 10 dB, peaking at 20 dB. This additional peak serves as a significant supplementary noise source near the stall point, leading to a maximum increase of 33.3 dB in the free radiated sound power. The acoustic response within the duct indicates that the compressor operating at the near-stall point continues to produce substantial noise on the actual test bench, showing an average increase of 6 dB in noise levels, and the distribution of the additional peak single-tone noise at the entrance significantly differs from that observed at the highest efficiency point.

Development and validation of a nomogram to predict the risk factors of major complications after radical rectal cancer surgery.

Purpose: The aim of this study was to establish a validated nomogram to predict risk factors for major post-operative complications in patients with rectal cancer (RC) by analyzing the factors contributing to major post-operative complications in RC patients. Methods: We retrospectively collected baseline and surgical information on patients who underwent RC surgery between December 2012 and December 2022 at a single-center teaching hospital. The entire cohort was randomly divided into two subsets (60% of the data for development, 40% for validation). Independent risk factors for major post-operative complications were identified using multivariate logistic regression analyses, and predictive models were developed. Area under the curve (AUC) was calculated using receiver operating characteristic curve (ROC) to assess predictive probability, calibration curves were plotted to compare the predicted probability of the nomogram with the actual probability, and the clinical efficacy of the nomogram was assessed using decision curve analysis (DCA). Results: Our study included 3151 patients who underwent radical surgery for RC, including 1892 in the development set and 1259 in the validation set. Forty (2.1%) patients in the development set and 26 (2.1%) patients in the validation set experienced major post-operative complications. Through multivariate logistic regression analysis, age (p<0.01, OR=1.044, 95% CI=1.016-1.074), pre-operative albumin (p<0.01, OR=0.913, 95% CI=0.866-0.964), and open surgery (p<0.01, OR=2.461, 95% CI=1.284-4.761) were identified as independent risk factors for major post-operative complications in RC, and a nomogram prediction model was established. The AUC of the ROC plot for the development set was 0.7161 (95% Cl=0.6397-0.7924), and the AUC of the ROC plot for the validation set was 0.7191 (95% CI=0.6182-0.8199). The predicted probabilities in the calibration curves were highly consistent with the actual probabilities, which indicated that the prediction model had good predictive ability. The DCA also confirmed the good clinical performance of the nomogram. Conclusion: In this study, a validated nomogram containing three predictors was created to identify risk factors for major complications after radical RC surgery. Due to its accuracy and convenience, it could contribute to personalized management of patients in the perioperative period.

Peiella sedimenti gen. nov., sp. nov., a novel taxon within the family Caulobacteraceae isolated from sediment of a river.

A Gram-stain-negative bacterium, designated XZ-24T, was isolated from sediment of a river in Mianyang city, Sichuan province, PR China. Cells (1.0-2.0 µm long and 0.4-0.5 µm in width) were strictly aerobic, non-spore-forming, rod shaped, prosthecate and motile by means of a polar flagellum. Growth occurred at 10-37 °C (optimum, 30 °C), at pH 5.0-9.0 (optimum pH 7.0) and with 0-3.0 % (w/v) NaCl (optimum 1.0 % NaCl). The results of phylogenetic analysis based on genomes and 16S rRNA gene sequences indicated that XZ-24T formed a distinct phyletic branch within the family Caulobacteraceae and was most closely related to members of the genera Brevundimonas, Caulobacter and Phenylobacterium with 95.3-96.5 % 16S rRNA gene sequence similarities. The average amino acid identities (AAI) between XZ-24T and species of the family Caulobacteraceae were 47.0-64.5 %, which were below the genus boundary (70 %). The predominant cellular fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0, C18 : 1ω7c 11-methyl and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), the isoprenoid quinone was Q-10, and the major polar lipids were 1,2-di-O-acyl-3-O-α-d-glucopyranuronosyl glycerol; 1,2-di-O-acyl-3-O-[d-glucopyranosyl-(1→4)-α-d glucopyranuronosyl] glycerol and phosphatidylglycerol. The genome size of XZ-24T was 2.64 Mb with a DNA G+C content of 68.9 %. On the basis of the evidence presented in this study, strain XZ-24T represents a novel species of a novel genus in the family Caulobacteraceae, for which the name Peiella sedimenti gen. nov., sp. nov. (Type strain XZ-24T=CCTCC AB 20 23 094T=KCTC 8038T) is proposed.

Multistress Interplay: Time and Duration of Ocean Acidification Modulate the Toxicity of Mercury and Other Metals.

The current understanding of multistress interplay assumes stresses occur in perfect synchrony, but this assumption is rarely met in the natural marine ecosystem. To understand the interplay between nonperfectly overlapped stresses in the ocean, we manipulated a multigenerational experiment (F0-F3) to explore how different temporal scenarios of ocean acidification will affect mercury toxicity in a marine copepod Pseudodiaptomus annandalei. We found that the scenario of past acidification aggravated mercury toxicity but current and persistent acidification mitigated its toxicity. We specifically performed a proteomics analysis for the copepods of F3. The results indicated that current and persistent acidification initiated the energy compensation for development and mercury efflux, whereas past acidification lacked the barrier of H+ and had dysfunction in the detoxification and efflux system, providing a mechanistic understanding of mercury toxicity under different acidification scenarios. Furthermore, we conducted a meta-analysis on marine animals, demonstrating that different acidification scenarios could alter the toxicity of several other metals, despite evidence from nonsynchronous scenarios remaining limited. Our study thus demonstrates that time and duration of ocean acidification modulate mercury toxicity in marine copepods and suggests that future studies should move beyond the oversimplified scenario of perfect synchrony in understanding multistress interaction.

Percutaneous cement-augmented short-segment pedicle screw fixation plus percutaneous vertebroplasty for stage III Kummell's disease without neurological symptoms: A case report.

INTRODUCTION: The incidence of stage III Kummell's disease without neurological symptoms is increasing in elderly patients with osteoporotic thoracolumbar fractures. However, the surgical method is still controversial in this condition. This report presented a case of Kummell's disease in which percutaneous bone cement-augmented short-segment pedicle screw fixation combined with percutaneous vertebroplasty was performed, providing a reference for the surgical approach. CASE PRESENTATION: The patient was a 72-year-old female who presented unexplained lower back pain accompanied with limited mobility for the past three months. Based on her medical history, physical examinations, and imaging studies, it was confirmed that she had Kummell's disease in stage III without neurological symptoms. We treated her with percutaneous bone cement-augmented short-segment pedicle screw fixation combined with percutaneous vertebroplasty on the symptomatic vertebrae. CLINICAL DISCUSSION: The majority of patients with stage III Kummell's disease have severe osteoporosis, which result in failure of the internal fixation and a series of other complications. Maintaining the stability of the internal fixation system is crucial, especially after screwing and subsequent locking. When augmented with bone cement, the grip and pull-out resistance of the percutaneous pedicle screws enhance greatly. Simultaneously, percutaneous vertebroplasty on the symptomatic vertebrae can immediately support the spine unit's stability mechanically and maintain the shape of the vertebrae after reduction. CONCLUSIONS: The percutaneous bone cement-augmented short-segment pedicle screw fixation combined with percutaneous vertebroplasty on the symptomatic vertebrae is an effective treatment for stage III Kummell's disease without neurological symptoms. It can effectively restore the vertebral height, correct the kyphotic deformities, improve spinal canal stenosis, and achieve satisfactory short-term clinical outcomes.

Applications of Tissue Clearing in Central and Peripheral Nerves.

The techniques of tissue clearing have been proposed and applied in anatomical and biomedical research since the 19th century. As we all know, the original study of the nervous system relied on serial ultrathin sections and stereoscopic techniques. The 3D visualization of the nervous system was established by software splicing and reconstruction. With the development of science and technology, microscope equipment had constantly been upgraded. Despite the great progress that has been made in this field, the workload is too complex, and it needs high technical requirements. Abundant mistakes due to manual sections were inescapable and structural integrity remained questionable. According to the classification of tissue transparency methods, we introduced the latest application of transparency methods in central and peripheral nerve research from optical imaging, molecular markers and data analysis. This review summarizes the application of transparent technology in neural pathways. We hope to provide some inspiration for the continuous optimization of tissue clearing methods.

New genes helped acorn barnacles adapt to a sessile lifestyle.

Barnacles are the only sessile lineages among crustaceans, and their sessile life begins with the settlement of swimming larvae (cyprids) and the formation of protective shells. These processes are crucial for adaptation to a sessile lifestyle, but the underlying molecular mechanisms remain poorly understood. While investigating these mechanisms in the acorn barnacle, Amphibalanus amphitrite, we discovered a new gene, bcs-6, which is involved in the energy metabolism of cyprid settlement and originated from a transposon by acquiring the promoter and cis-regulatory element. Unlike mollusks, the barnacle shell comprises alternate layers of chitin and calcite and requires another new gene, bsf, which generates silk-like fibers that efficiently bind chitin and aggregate calcite in the aquatic environment. Our findings highlight the importance of exploring new genes in unique adaptative scenarios, and the results will provide important insights into gene origin and material development.