Alterations of resting-state network dynamics in Alzheimer's disease based on leading eigenvector dynamics analysis.

Alzheimer's disease (AD) is a neurodegenerative disease, and mild cognitive impairment (MCI) is considered a transitional stage between healthy aging and dementia. Early detection of MCI can help slow down the progression of AD. At present, there are few studies exploring the characteristics of abnormal dynamic brain activity in AD. This article uses a method called Leading Eigenvector Dynamics Analysis (LEiDA) to study resting-state functional magnetic resonance imaging (rs-fMRI) data of AD, MCI, and cognitively normal (CN) participants. By identifying repetitive states of phase coherence, inter group differences in brain dynamic activity indicators are examined. And the neurobehavioral scales were used to assess the relationship between abnormal dynamic activities and cognitive function. The results showed that in the indicators of occurrence probability and lifetime, the globally synchronized state of the patient group decreased. The activity state of the limbic regions significantly detected the difference between AD and the other two groups. Compared to CN, AD and MCI have varying degrees of increase in default and visual regions activity states. In addition, in the analysis related to the cognitive scales, it was found that individuals with poorer cognitive abilities were less active in the globally synchronized state, and more active in limbic regions activity state and visual regions activity state. Taken together, these findings reveal abnormal dynamic activity of resting-state networks in patients with AD and MCI, provide new insights into the dynamic analysis of brain networks, and contribute to a deeper understanding of abnormal spatial dynamic patterns in AD patients.

The Effects of Posture on Mind Wandering.

Using two executive tasks, we explored how body posture influences mind wandering, a universal internally self-generated activity. Specifically, participants were instructed to perform the Sustained Attention Response Task (SART) and the Flanker task under three postural conditions: lying supine, sitting, and standing upright. These tasks reflect the proactive and reactive modes of executive control, respectively. To measure the frequency of mind wandering, we employed the probe-caught technique, presenting prompts at irregular intervals. The results indicate that, compared to standing and sitting positions, lying supine significantly increased mind wandering, while posture had no effect on either measure of executive control. We suggest that changes in posture alter cognitive activity related to self-generated thoughts and external tasks, whereas the relationship between mind wandering and executive control requires further research.

Interfacial multilayer self-assembly of protein and polysaccharides: Ultrasonic regulation, stability and application in delivery lutein.

In this study, the layer-by-layer adsorption behavior of sodium caseinate, pectin, and chitosan on the oil-water interface was illustrated using multi-frequency ultrasound. We investigated the impact of ultrasound on various factors, such as particle size, zeta potential, and interfacial protein/polysaccharide concentration. It was observed that ultrasound has significantly decreased droplet size and increased the surface area at the interface, hence promoting the adsorption of protein/polysaccharide. In the sonicated multilayer emulsion, the concentrations of interface proteins, pectin, and chitosan increased to 84.82 %, 90.49 %, and 83.31 %, respectively. The findings of the study indicated that the application of ultrasonic treatment had a significant impact on the emulsion's surface charge and the prevention of droplet aggregation. As a result, the stability of the emulsion system, including its resistance to salt, temperature, and storage conditions, has been significantly improved. Moreover, the emulsion showed an increase in the retention rate of lutein by 21.88 % after a high-temperature water bath and by 19.35 % after UV irradiation. Certainly, the multilayer emulsion treated with ultrasound demonstrated a superior and prolonged releasing behavior. These findings demonstrated the suitability of the ultrasound treatment for the preparation of emulsions to deliver bioactive compounds.

Preparation and functional characterization of pullulan-sodium alginate composite film enhanced with ultrasound-assisted clove essential oil Nanoemulsions for effective preservation of cherries and mushrooms.

Clove essential oil (CEO) exhibited potent antibacterial efficacy and are obtained from Eugenia caryophyllata tree flower buds. Herein, CEO nanoemulsions were prepared using various concentrations of casein protein treated with ultrasound for different time interval. The study demonstrated that CEO nanoemulsions with 5% casein protein subjected to ultrasound for 10 min displayed the most minimal particle size. The pullulan­sodium alginate film incorporated with nanoemulsions treated with ultrasound exhibited enhanced physico-mechanical characteristics. Based on the structural analysis, the application of ultrasonic treatment improved intermolecular compatibility and organized molecular structure by strengthening hydrogen bonds. Furthermore, the composite film displayed remarkable efficacy against E. coli and S. aureus as well as longer retention of essential oils. The use of the developed films to protect cherry fruits and mushrooms produced promising results, emphasizing their potential in food packaging applications.

Development of a nanoparticle-based tendon-targeting drug delivery system to pharmacologically modulate tendon healing.

Satisfactory healing following acute tendon injury is marred by fibrosis. Despite the high frequency of tendon injuries and poor outcomes, there are no pharmacological therapies in use to enhance the healing process. Moreover, systemic treatments demonstrate poor tendon homing, limiting the beneficial effects of potential tendon therapeutics. To address this unmet need, we leveraged our existing tendon healing spatial transcriptomics dataset and identified an area enriched for expression of Acp5 (TRAP) and subsequently demonstrated robust TRAP activity in the healing tendon. This unexpected finding allowed us to refine and apply our existing TRAP binding peptide (TBP) functionalized nanoparticle (NP) drug delivery system (DDS) to facilitate improved delivery of systemic treatments to the healing tendon. To demonstrate the translational potential of this DDS, we delivered niclosamide (NEN), an S100a4 inhibitor. While systemic delivery of free NEN did not alter healing, TBP-NPNEN enhanced both functional and mechanical recovery, demonstrating the translational potential of this approach to enhance the tendon healing process.

Changes in characteristics and risk of freshwater microplastics under global warming.

Microplastics present a significant threat to freshwater ecosystems. However, the impact of global warming on their characteristics and associated risks remains uncertain. This study collected 2793 sample sites from literature and datasets to create a new risk assessment and rank methodology, known as the Multi-characteristics Potential Ecological Risk Index (MPERI), which incorporates various microplastic characteristics, such as concentration, size distribution, color, shape, and polymer diversity. Using regression random forest models (RRF), this study predicted that a 10 °C increase would raise microplastic concentration from 12,465.34 ± 68,603.87 to 13,387.17 ± 60,692.96 particles/m3. The percentage of small-size microplastics initially decreased (from 69.10 % to 68.72 %) and then increased (from 68.72 % to 68.78 %), while the diversity of color, shape, and polymer decreased by 0.29 %, 3.24 %, and 0.17 %, respectively. Furthermore, global warming could increase the rank of microplastic risks from high (405.25 ± 528.9) to dangerous (535.37 ± 582.03) based on the MPERI method. Most countries would experience an increase in risk values, with Indonesia and Vietnam transitioning from low to medium risk, and China and Malaysia transitioning from high to dangerous risk. The feature importance assessment of the RRF model indicated that concentration was the most influential variable in determining the change in risk values. While other microplastic characteristics had a lesser impact compared to concentration, they still influenced the risk ranking. This study highlights the role of global warming in shaping microplastic risks.

Hederagenol improves multiple sclerosis by modulating Th17 cell differentiation.

Multiple sclerosis (MS) is a common autoimmune illness that is difficult to treat. The upregulation of Th17 cells is critical in the pathological process of MS. Hederagenol (Hed) has been shown to lower IL-17 levels, although its role in MS pathophysiology is uncertain. In this study, we explore whether Hed could ameliorate MS by modulating Th17 cell differentiation, with the goal of identifying new treatment targets for MS. The experimental autoimmune encephalomyelitis (EAE) mouse model was conducted and Hed was intraperitoneally injected into mice. The weight was recorded and the clinical symptom grade was assessed. Hematoxylin-eosin staining was carried out to determine the extent of inflammation in the spinal cord and liver. The luxol Fast Blue staining was performed to detect the pathological changes in the myelin sheath. Nerve damage was detected using NeuN immunofluorescence staining and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. Immunohistology approaches were used to study alterations in immune cells in the spinal cord. The proportions of T cell subsets in the spleens were analyzed by flow cytometry. RORγt levels were measured using quantitative real-time PCR or Western blot. The activity of the RORγt promoter was analyzed by Chromatin immunoprecipitation. Hed administration reduced the clinical symptom grade of EAE mice, as well as the inflammatory infiltration, demyelination, and cell disorder of the spinal cord, while having no discernible effect on the mouse weight. In addition, Hed treatment significantly reduced the number of T cells, particularly Th17 cells in the spinal cord and spleen-isolated CD4+ T cells. Hed lowered the RORγt levels in spleens and CD4+ T cells and overexpression of RORγt reversed the inhibitory effect of Hed on Th17 differentiation. Hed decreased nerve injury by modulating Th17 differentiation through the RORγt promoter. Hed regulates Th17 differentiation by reducing RORγt promoter activity, which reduces nerve injury and alleviates EAE.

Reduction of relative intensity noise in a diamond Raman laser.

The relative intensity noise (RIN) characteristics of a continuous-wave diamond Raman laser are investigated for the first time. The results reveal the parasitic stimulated Brillouin scattering (SBS) that usually occurred with higher-order spatial modes in the diamond Raman resonator is a pivotal factor impacting the Raman longitudinal modes and deteriorating the RIN level. The diamond Raman laser automatically switches to single-longitudinal-mode operation and the RIN level is significantly decreased in the frequency range of 200 Hz to 1 MHz after the parasitic SBS is effectively suppressed through inserting a spatial aperture or a χ(2) nonlinear crystal into the cavity. Due to the introduction of additional nonlinear loss to the high intensity Raman fluctuations and the non-lasing spontaneous Raman modes, the χ(2) nonlinear crystal enables better performance in the RIN-level reduction compared to the spatial aperture which can only achieve SBS inhibition. The RIN reduction routes are well suited for various crystalline Raman media to achieve high power and low intensity noise laser at different wavelengths.

The association between dietary vitamin B1 intake and constipation: a population-based study.

BACKGROUND: Numerous researches have indicated a correlation between the intake of dietary micronutrients and the occurrence of constipation. Nevertheless, the correlation between constipation and vitamin B1 remains uninvestigated. The main aim of this research was to examine the association between chronic constipation and the consumption of vitamin B1 in the diet among adult participants of the National Health and Nutrition Examination Survey (NHANES). METHODS: This study used data from the NHANES, a survey on health and nutrition conducted between 2005 and 2010. The respondents' dietary information was gathered by utilizing the 24-hour dietary records. Various statistical analyses, such as multiple logistic regression, subgroup analysis, and curve-fitting analysis, were employed to investigate the correlation between dietary intake of vitamin B1 and chronic constipation. RESULTS: In the trial, there were 10,371 participants, out of which 1,123 individuals (10.8%) were identified as having chronic constipation. Fully adjusted multiple logistic regression analyses showed that increasing dietary intake of vitamin B1 (OR = 0.87, 95% CI: 0.77-0.99) was significantly associated with a reduced risk of constipation. Following adjustment for multiple variables in Model 3, the odds ratio (OR) and 95% confidence interval (CI) for the third tertile, in comparison to the first tertile (reference group), was 0.80 (0.65, 0.99). In addition, subgroup analyses and interaction tests showed a significant inverse association between vitamin B1 intake and the prevalence of constipation, especially among men, non-hypertensive, and non-diabetic individuals (all P-values less than 0.05). CONCLUSION: This research uncovered an inverse correlation between the consumption of vitamin B1 in the diet and the occurrence of chronic constipation. One potential explanation for this phenomenon is that the consumption of vitamin B1 in one's diet is linked to the softening of stools and an augmented occurrence of colonic peristalsis. Additional extensive prospective research is required to thoroughly examine the significance of thiamine in long-term constipation.

Association between omega-3 polyunsaturated fatty acids and osteoarthritis: results from the NHANES 2003-2016 and Mendelian randomization study.

BACKGROUND: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) exhibit potential as therapeutics for a variety of diseases. This observational and Mendelian randomization (MR) study aims to explore the relationship between omega-3 PUFAs and osteoarthritis (OA). METHODS: Excluding individuals under 20 years old and those with missing data on relevant variables in the National Health and Nutrition Examination Survey (NHANES) spanning from 2003 to 2016, a total of 22 834 participants were included in this cross-sectional study. Weighted multivariable-adjusted logistic regression was used to estimate the association between omega-3 PUFAs and OA in adults. Moreover, restricted cubic splines were utilized to examine the dose-response relationship between omega-3 PUFAs and OA. To further investigate the potential causal relationship between omega-3 PUFAs and OA risk, a two-sample MR study was conducted. Furthermore, the robustness of the findings was assessed using various methods. RESULTS: Omega-3 PUFAs intake were inversely associated with OA in adults aged 40 ∼ 59 after multivariable adjustment [Formula: see text], with a nonlinear relationship observed between omega-3 PUFAs intake and OA [Formula: see text]. The IVW results showed there was no evidence to suggest a causal relationship between omega-3 PUFAs and OA risk [Formula: see text]. CONCLUSIONS: Omega-3 PUFAs were inversely associated with OA in adults aged 40 ∼ 59. However, MR studies did not confirm a causal relationship between the two.

Theoretical Investigation on the Reversible Photoswitch Mechanism of Benzylidene-Oxazolone System.

The design and application of molecular photoswitches have attracted much attention. Herein, we performed a detailed computational study on the photoswitch benzylidene-oxazolone system based on static electronic structure calculations and on-the-fly excited-state dynamic simulations. For the Z and E isomer, we located six and four minimum energy conical intersections (MECIs) between the first excited state (S1) and the ground state (S0), respectively. Among them, the relaxation pathway driven by ring-puckering motion is the most competitive channel with the photoisomeization process, leading to the low photoisomerization quantum yield. In the dynamic simulations, about 88 % and 66 % trajectories decays from S1 to S0 for Z and E isomer, respectively within the total simulation time of ~2 ps. The photoisomeization quantum yields obtained in our study (0.20 for Z→E and 0.12 for E→Z) agree well with the experimental measured values (0.25 and 0.11), even though the number of trajectories are limited to 50. Our study sheds light on the complexity of the benzylidene-oxazolone system 's deactivation process and the competitive mechanisms among different reaction channels, which provide theoretical guidance for further design and development of benzylidene-oxazolone based molecular photoswitches.

SzM protein of Streptococcus equi ssp. zooepidemicus triggers the release of neutrophil extracellular traps depending on GSDMD.

Streptococcus equissp.zooepidemicus (SEZ) is a crucial pathogen and contributes to various infections in numerous animal species. Swine streptococcicosis outbreak caused by SEZ has been reported in several countries in recent years. SzM protein is a cell membrane-anchored protein, which exhibits as an important virulence factor of SEZ. Effects of SzM protein on host innate immune need further study. Here, recombinant SzM (rSzM) protein of the SEZ was obtained, and mice were intraperitoneally injected with rSzM protein. We discovered that rSzM protein can recruit neutrophils into the injected site. In further study, neutrophils were isolated and treated with rSzM protein, NETs release were triggered by rSzM protein independently, and GSDMD protein was promoted-expressed and activated. In order to investigate the role of GSDMD in NETs formation, neutrophils isolated from WT mice and GSDMD-/- mice were treated with rSzM protein. The results showed that GSDMD deficiency suppressed the NETs release. In conclusion, SzM protein of SEZ can trigger the NETs release in a GSDMD-depending manner.

Inhibiting Residual Solvent Induced Side Reactions in Vinylidene Fluoride-Based Polymer Electrolytes Enables Ultra-Stable Solid-State Lithium Metal Batteries.

Residual solvents in vinylidene fluoride (VDF)-based solid polymer electrolytes (SPEs) have been recognized as responsible for their high ionic conductivity. However, side reactions by the residual solvents with the lithium (Li) metal induce poor stability, which has been long neglected. This study proposes a strategy to achieve a delicate equilibrium between ion conduction and electrode stability for VDF-based SPEs. Specifically, 2,2,2-trifluoro-N,N-dimethylacetamide (FDMA) is developed as the nonside reaction solvent for poly(vinylidene fluoride-co-hexafluoropropylene) (PVHF)-based SPEs, achieving both high ionic conductivity and significantly improved electrochemical stability. The developed FDMA solvent fosters the formation of a stable solid electrolyte interphase (SEI) through interface reactions with Li metal, effectively mitigating side reactions and dendrite growth on the Li metal electrode. Consequently, the Li||Li symmetric cells and Li||LiFePO4 cells demonstrate excellent cycling performance, even under limited Li (20 µm thick) supply and high-loading cathodes (>10 mg cm-2, capacity >1 mAh cm-2) conditions. The stable Li||LiCoO2 cells operation with a cutoff voltage of 4.48 V indicates the high-voltage stability of the developed SPE. This study offers valuable insights into the development of advanced VDF-based SPEs for enhanced lithium metal battery performance and longevity.

LILRB4 represents a promising target for immunotherapy by dual targeting tumor cells and myeloid-derived suppressive cells in multiple myeloma.

Multiple myeloma (MM) remains an incurable hematological malignancy. Despite tremendous advances in the treatment, about 10% of patients still have very poor outcomes with median overall survival less than 24 months. Our study aimed to underscore the critical mechanisms pertaining to the rapid disease progression and provide novel therapeutic selection for these ultra-high-risk patients. We utilized single-cell transcriptomic sequencing to dissect the characteristic bone marrow niche of patients with survival of less than two years (EM24). Notably, an enrichment of LILRB4high pre-matured plasma-cell cluster was observed in the patients in EM24 compared to patients with durable remission. This cluster exhibited aggressive proliferation and drug-resistance phenotype. High-level LILRB4 promoted MM clonogenicity and progression. Clinically, high expression of LILRB4 was correlated with poor prognosis in both newly diagnosed MM patients and relapsed/refractory MM patients. The ATAC-seq analysis identified that high chromosomal accessibility caused the elevation of LILRB4 on MM cells. CRISPR-Cas9 deletion of LILRB4 alleviated the growth of MM cells, inhibited the immunosuppressive function of MDSCs, and further rescued T cell dysfunction in MM microenvironment. The more infiltration of myeloid-derived suppressive cells (MDSCs) was observed in EM24 patients as well. Therefore, we innovatively generated a TCR-based chimeric antigen receptor (CAR) T cell, LILRB4-STAR-T. Cytotoxicity experiment demonstrated that LILRB4-STAR-T cells efficaciously eliminated tumor cells and impeded MDSCs function. In conclusion, our study elucidates that LILRB4 is an ideal biomarker and promising immunotherapy target for high-risk MM. LILRB4-STAR-T cell immunotherapy is promising against tumor cells and immunosuppressive tumor microenvironment in MM.

Energy Metabolism: From Physiological Changes to Targets in Sepsis-induced Cardiomyopathy.

Sepsis is a systemic inflammatory response syndrome caused by a variety of dysregulated responses to host infection with life-threatening multi-organ dysfunction. Among the injuries or dysfunctions involved in the course of sepsis, cardiac injury and dysfunction often occur and are associated with the pathogenesis of hemodynamic disturbances, also defined as sepsis-induced cardiomyopathy (SIC). The process of myocardial metabolism is tightly regulated and adapts to various cardiac output demands. The heart is a metabolically flexible organ capable of utilizing all classes of energy substrates, including carbohydrates, lipids, amino acids, and ketone bodies to produce ATP. The demand of cardiac cells for energy metabolism changes substantially in septic cardiomyopathy with distinct etiological causes and different times. This review describes changes in cardiomyocyte energy metabolism under normal physiological conditions and some features of myocardial energy metabolism in septic cardiomyopathy, and briefly outlines the role of the mitochondria as a center of energy metabolism in the septic myocardium, revealing that changes in energy metabolism can serve as a potential future therapy for infectious cardiomyopathy.

The Chain Mediating Role of Teachers' Job Stress in the Influence of Distributed School Leadership on Job Satisfaction: Evidence from China, the United States, England, and Australia.

Distributed leadership has been shown to improve teacher job satisfaction and reduce teacher job stress. However, few studies have thoroughly explored the indirect effects of distributed leadership on increasing the teachers' burden in school administration and management, thereby increasing work stress, and decreasing job satisfaction. Data from the Teaching and Learning International Survey were analyzed to investigate the relationships among distributed school leadership, teachers' job stress, and job satisfaction. A total of 3976 teachers from 198 junior high schools in Shanghai, 2560 teachers from 166 junior high schools in the United States, 2376 teachers from 157 junior high schools in England, and 3573 teachers from 238 junior high schools in Australia were selected and examined using structural equation modeling. The results revealed that distributed school leadership directly predicted teachers' job satisfaction; teachers' job stress had an independent mediating effect on distributed leadership and teachers' job satisfaction, whereas teachers' time spent participating in school leadership had no mediating effect. We discuss the benefits of distributed school leadership on teachers' job satisfaction and the possible mechanisms for promoting it in practice.

Review: The application of source analysis methods in tracing urban non-point source pollution: categorization, hotspots, and future prospects.

The contribution of urban non-point source (NPS) pollution to surface water pollution has gradually increased, analyzing the sources of urban NPS pollution is of great significance for precisely controlling surface water pollution. A bibliometric analysis of relevant research literature from 2000 to 2021 reveals that the main methods used in the source analysis research of urban NPS pollution include the emission inventory approach, entry-exit mass balance approach, principal component analysis (PCA), positive matrix factorization (PMF) model, etc. These methods are primarily applied in three aspects: source analysis of rainfall-runoff pollution, source analysis of wet weather flow (WWF) pollution in combined sewers, and analysis of the contribution of urban NPS to the surface water pollution load. The application of source analysis methods in urban NPS pollution research has demonstrated an evolution from qualitative to quantitative, and further towards precise quantification. This progression has transitioned from predominantly relying on on-site monitoring to incorporating model simulations and employing mathematical statistical analyses for traceability. This paper reviews the principles, advantages, disadvantages, and the scope of application of these methods. It also aims to address existing problems and analyze potential future development directions, providing valuable references for subsequent related research.

Temporal dynamics of stress response in Halomonas elongata to NaCl shock: physiological, metabolomic, and transcriptomic insights.

BACKGROUND: The halophilic bacterium Halomonas elongata is an industrially important strain for ectoine production, with high value and intense research focus. While existing studies primarily delve into the adaptive mechanisms of this bacterium under fixed salt concentrations, there is a notable dearth of attention regarding its response to fluctuating saline environments. Consequently, the stress response of H. elongata to salt shock remains inadequately understood. RESULTS: This study investigated the stress response mechanism of H. elongata when exposed to NaCl shock at short- and long-time scales. Results showed that NaCl shock induced two major stresses, namely osmotic stress and oxidative stress. In response to the former, within the cell's tolerable range (1-8% NaCl shock), H. elongata urgently balanced the surging osmotic pressure by uptaking sodium and potassium ions and augmenting intracellular amino acid pools, particularly glutamate and glutamine. However, ectoine content started to increase until 20 min post-shock, rapidly becoming the dominant osmoprotectant, and reaching the maximum productivity (1450 ± 99 mg/L/h). Transcriptomic data also confirmed the delayed response in ectoine biosynthesis, and we speculate that this might be attributed to an intracellular energy crisis caused by NaCl shock. In response to oxidative stress, transcription factor cysB was significantly upregulated, positively regulating the sulfur metabolism and cysteine biosynthesis. Furthermore, the upregulation of the crucial peroxidase gene (HELO_RS18165) and the simultaneous enhancement of peroxidase (POD) and catalase (CAT) activities collectively constitute the antioxidant defense in H. elongata following shock. When exceeding the tolerance threshold of H. elongata (1-13% NaCl shock), the sustained compromised energy status, resulting from the pronounced inhibition of the respiratory chain and ATP synthase, may be a crucial factor leading to the stagnation of both cell growth and ectoine biosynthesis. CONCLUSIONS: This study conducted a comprehensive analysis of H. elongata's stress response to NaCl shock at multiple scales. It extends the understanding of stress response of halophilic bacteria to NaCl shock and provides promising theoretical insights to guide future improvements in optimizing industrial ectoine production.

A chromosome-level genome assembly of the pig-nosed turtle (Carettochelys insculpta).

The pig-nosed turtle (Carettochelys insculpta) represents the only extant species within the Carettochelyidae family, is a unique Trionychia member fully adapted to aquatic life and currently facing endangerment. To enhance our understanding of this species and contribute to its conservation efforts, we employed high-fidelity (HiFi) and Hi-C sequencing technology to generate its genome assembly at the chromosome level. The assembly result spans 2.18 Gb, with a contig N50 of 126 Mb, encompassing 34 chromosomes that account for 99.6% of the genome. The assembly has a BUSCO score above 95% with different databases and strong collinearity with Yangtze giant softshell turtles (Rafetus swinhoei), indicating its completeness and continuity. A total of 19,175 genes and 46.86% repetitive sequences were annotated. The availability of this chromosome-scale genome represents a valuable resource for the pig-nosed turtle, providing insights into its aquatic adaptation and serving as a foundation for future turtle research.