Responses of biomarkers, joint effect and drilosphere bacterial communities to antimony (III and/or V) contamination.

Contamination of soils with antimony (Sb) is becoming increasingly severe and widespread, and the associated ecological risks cannot be ignored. To evaluate how different Sb forms affected the earthworm Eisenia fetida in soil, the biomarker response index (BRI), effect addition index (EAI), and microbial diversity were characterized after single and joint application of Sb(III) and Sb(V). The results showed that Sb(III) was better enriched by earthworms than Sb(V). The metallothionein (MT) content in earthworms increased under Sb stress, and the superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST) activities also showed an increasing trend, suggesting waken-up antioxidant capacity. Severe alterations for health status were observed under combined treatment. Additionally, the EAI indicated that Sb(III) and Sb(V) had synergistic and antagonistic effects at low and high concentrations, respectively. The bacterial populations in the drilosphere (gut and burrow lining) appeared to be more susceptible to Sb contamination than in the non-drilosphere, their specific microecology may be an important factor in soil Sb migration and transformation. The abundance of Actinobacteria exhibited a significant decrease with increasing concentrations of single Sb(III) and Sb(V), while the abundance of Bacteroidia increased. The correlation heatmap showed that Sphingobacterium faecium was highly tolerant to Sb. These results provide not only an important basis for the ecological risk assessment of Sb in the soil environment but also new insights into the altered drilosphere bacterial communities under Sb stress.

The Preventive and Therapeutic Effects of Acute and Severe Inflammatory Disorders with Heparin and Heparinoid.

Systematic inflammatory response syndrome (SIRS) and the accompanying sepsis pose a huge threat to human health worldwide. Heparin is a part of the standard supportive care for the disease. However, the molecular mechanism is not fully understood yet, and the potential signaling pathways that play key roles have not yet been elucidated. In this paper, the main findings regarding the molecular mechanisms associated with the beneficial effects of heparin, including inhibiting HMGB-1-driven inflammation reactions, histone-induced toxicity, thrombo-inflammatory response control and the new emerging mechanisms are concluded. To set up the link between the preclinical research and the clinical effects, the outcomes of the clinical trials are summarized. Then, the structure and function relationship of heparin is discussed. By providing an updated analysis of the above results, the paper highlights the feasibility of heparin as a possible alternative for sepsis prophylaxis and therapy.

E3 Ubiquitin Ligase CHIP Inhibits Haemocyte Proliferation and Differentiation via the Ubiquitination of Runx in the Pacific Oyster.

Mollusca first evolve primitive immune cells (namely, haemocytes), which assemble a notable complex innate immune system, which are continuously produced through proliferation and differentiation and infused in the haemolymph. As a typical E3 ligase, CHIP is critical for immune cell turnover and homeostasis in vertebrates. In this study, a CHIP homolog (CgCHIP) with a high expression in haemocytes was identified in oysters to investigate its role in the proliferation and differentiation of ancient innate immune cells. CgCHIP exhibited a widespread distribution across all haemocyte subpopulations, and the knockdown of CgCHIP altered the composition of haemocytes as examined by flow cytometry. Mechanistically screened with bioinformatics and immunoprecipitation, a key haematopoietic transcription factor CgRunx was identified as a substrate of CgCHIP. Moreover, amino acids in the interacted intervals of CgCHIP and CgRunx were determined by molecular docking. Experimental evidence from an in vitro culture model of an agranulocyte subpopulation and an in vivo oyster model revealed that the knockdown of CgCHIP and CgRunx had opposing effects on agranulocyte (precursor cells) differentiation and granulocyte (effector cells) proliferation. In summary, CgCHIP negatively regulated agranulocyte differentiation and granulocyte proliferation by mediating the ubiquitination and degradation of CgRunx in oysters. These results offer insight into the involvement of ubiquitylation in controlling haemocyte turnover in primitive invertebrates.

Global burden of lung cancer in women of childbearing age attributable to ambient particulate matter pollution: 1990-2021.

BACKGROUND: This study aimed to evaluate the global burden of lung cancer due to ambient particulate matter (PM) pollution in women of childbearing age from 1990 to 2021. METHODS: This was a secondary analysis utilizing data from the Global Burden of Disease (GBD) 2021, with a focus on the temporal trends of the lung cancer burden attributable to ambient PM2.5 among women of childbearing age. RESULTS: In 2021, the global mortality and disability-adjusted life years (DALYs) number of lung cancer burden attributable to ambient PM2.5 among women of childbearing age were approximately 5205 and 247,211, respectively. The rate of lung cancer attributable to ambient PM2.5 among women of childbearing age increased between 1990 and 2021, with the age-standardized mortality rate (ASMR) increasing from 0.22 (95% uncertainty interval [UI]; 0.13 to 0.33) to 0.25 (95% UI; 0.14 to 0.37; average annual percent change [AAPC] = 0.40) and the age-standardized DALYs rate (ASDR) increasing from 10.39 (95% UI; 5.96 to 15.72) to 12.06 (95% UI; 6.83 to 17.51; AAPC = 0.41). The middle sociodemographic index (SDI) region, East Asia, and China had the heaviest burden, while the high SDI region showed the highest decrease. ASMR and ASDR exhibited an inverted U-shaped relationship with the SDI. CONCLUSIONS: From 1990 to 2021, the lung cancer burden attributable to ambient PM2.5 among women of childbearing age exhibited an increasing trend. Furthermore, increasing attention should be paid to the middle SDI region, East Asia, and China, as ambient PM pollution remains a critical target for intervention.

Vkorc1 polymorphisms of the Norway rats in China: Implications for rodent management and evolutionary origin of anticoagulant resistance mutations.

The extensive utilization of second-generation anticoagulant rodenticides (SGARs) has raised concerns regarding non-target animal safety and environmental contamination. It is essential to assess the anticoagulant resistance level in rodent populations and prioritize the use of relative low toxic first-generation anticoagulant rodenticides (FGARs) in susceptible rodent populations. Mutations in the vitamin K epoxide reductase complex subunit 1 (Vkorc1) gene confer anticoagulant resistance in Norway rats. However, the Vkorc1 polymorphisms remain unclear in most Norway rat populations in China although anticoagulant rodenticides have been widely used in China since the 1980s. Analysis of the Vkorc1 polymorphisms in 489 rats across China, combined with in silico binding affinity analysis, revealed three potential resistance mutations A26T, C96Y, and A140T at three distinct locations. In the remaining locations, Vkorc1 resistance mutations were absent, indicating that the FGARs could be effective in these areas. Additional evolutionary analysis of different Vkorc1 mutations suggested that the three missense mutations identified in China might have evolved independently as de novo mutations, and the resistance mutations in Europe are unlikely to be pre-existing variations in China. Further analysis of Vkorc1 haplotypes among European resistant rat populations is essential for understanding the origin of these resistance mutations. These findings emphasize the importance of customizing rodent control strategies in China based on regional resistance levels and gaining insights into the origins of Vkorc1 mutations for more effective rodent management strategies.

Ultra-wide-angle multispectral narrow-band absorber for infrared spectral reconstruction.

This paper presents the design of an ultra-wide-angle multispectral narrow-band absorber for reconstructing infrared spectra. The absorber offers several advantages, including polarization sensitivity, robustness against structural wear, wide azimuthal angle coverage, high narrow-band absorption, and adjustable working wavelength. To accomplish infrared spectrum reconstruction, an absorber is employed as a spectral sampling channel, eliminating the influence of slits or complex optical splitting elements in spectral imaging technology. Additionally, we propose using a truncation regularization algorithm based on the design matrix singular value ratio, namely IReg, which can enable high-precision spectral reconstruction under largely disturbed environments. The results demonstrate that, even when the number of absorption spectrum curve is reduced to a range of 1/2 to 1/3, high-precision spectral reconstruction is achievable for both flat and high-energy steep mid- and long-infrared spectral targets, while effectively accomplishing data dimension reduction.

Construction and validation of a novel forecasting nomogram to the risk of colorectal adenomas: preventing colorectal cancer at its origin.

Colorectal adenomas are responsible for the origin of most colorectal cancers (CRC). Early detection together with active intervention of colorectal adenomas plays a crucial role in the prevention of colorectal cancer. This study aimed to construct and validate a new nomogram for the forecasting of the risk of colorectal adenomas based on lifestyle risk factors that could offer potential benefits for CRC prevention. Colonoscopy reports, pathology reports, physical factors, family history, personal history of disease, diet, and lifestyle habits were collected from 1133 subjects who underwent complete colonoscopy. All subjects were divided into the training cohort (n = 792) and the validation cohort (n = 341). A nomogram predicting the risk of colorectal adenoma development was constructed using the training cohort and the C-index was calculated. The predictive accuracy and clinical applicability of the nomogram were verified in the validation cohort. The nomogram was constructed by 6 statistically significant variables selected from 18 health factors, including advanced age, male, smoking, drinking, pickles, and irregular defecation. The C-index of the training cohort was 0.778 and the C-index of the validation cohort was 0.754. The calibration curve and decision curve analysis (DCA) also confirmed that the model has good predictive ability and high profit. The nomogram constructed in this study was validated and can be applied to predicting the occurrence risk of colorectal adenoma. The model can guide the identification of patients with non-symptomatic colorectal adenomas and the recognition of high-risk individuals for whom a colonoscopy is advisable.

Cell-cell communication: new insights and clinical implications.

Multicellular organisms are composed of diverse cell types that must coordinate their behaviors through communication. Cell-cell communication (CCC) is essential for growth, development, differentiation, tissue and organ formation, maintenance, and physiological regulation. Cells communicate through direct contact or at a distance using ligand-receptor interactions. So cellular communication encompasses two essential processes: cell signal conduction for generation and intercellular transmission of signals, and cell signal transduction for reception and procession of signals. Deciphering intercellular communication networks is critical for understanding cell differentiation, development, and metabolism. First, we comprehensively review the historical milestones in CCC studies, followed by a detailed description of the mechanisms of signal molecule transmission and the importance of the main signaling pathways they mediate in maintaining biological functions. Then we systematically introduce a series of human diseases caused by abnormalities in cell communication and their progress in clinical applications. Finally, we summarize various methods for monitoring cell interactions, including cell imaging, proximity-based chemical labeling, mechanical force analysis, downstream analysis strategies, and single-cell technologies. These methods aim to illustrate how biological functions depend on these interactions and the complexity of their regulatory signaling pathways to regulate crucial physiological processes, including tissue homeostasis, cell development, and immune responses in diseases. In addition, this review enhances our understanding of the biological processes that occur after cell-cell binding, highlighting its application in discovering new therapeutic targets and biomarkers related to precision medicine. This collective understanding provides a foundation for developing new targeted drugs and personalized treatments.

Supportive Psychotherapy Combined with Analgesic Management can Effectively Improve Pain and Quality of Life in Patients with Advanced Prostate Cancer: A Retrospective Study.

OBJECTIVE: Patients with advanced prostate cancer commonly experience psychological issues and have a low quality of life. This study aims to analyse the application of supportive psychotherapy combined with analgesic management on the pain and quality of life of patients with advanced prostate cancer. METHODS: Patients with advanced prostate cancer admitted to our hospital from February 2018 to December 2022 were continuously selected as the research objects. In accordance with the different management methods recorded in the medical record system, the patients were divided into a control group (routine nursing + analgesic management) and an observation group (routine nursing + analgesic management + supportive psychotherapy). The Athens Insomnia Scale (AIS), State Anxiety Scale (S-AI), Trait Anxiety Scale (T-AI), Numeric Rating Scale (NRS) and 36-Item Short-Form Health Survey (SF-36) scores between the two groups were compared. RESULTS: A total of 125 patients with advanced prostate cancer participated in this study, with 60 patients in the control group and 65 patients in the observation group. No significant difference was found in the scores of the AIS, S-AI, T-AI, NRS and SF-36 of the two groups before management (p > 0.05). After management, the AIS (4.00 vs. 5.00, p = 0.002), S-AI (38.88 vs. 41.12, p = 0.002), T-AI (39.17 vs. 41.65, p = 0.001) and NRS (3.00 vs. 3.00, p < 0.001) scores of the observation group were lower than those of the control group. However, the SF-36 scores of the observation group were higher than those of the control group in the dimensions of physiological enginery (75.85 vs. 68.75, p < 0.001), physiological function (71.85 vs. 67.75, p = 0.004), body pain (73.15 vs. 69.33, p = 0.006), social function (73.88 vs. 69.85, p = 0.004), emotional function (72.92 vs. 68.98, p = 0.006), mental health (73.52 vs. 69.83, p = 0.008), vitality (72.09 vs. 69.52, p = 0.044) and general health (70.65 vs. 66.23, p = 0.002). CONCLUSIONS: Supportive psychotherapy combined with analgesic management for patients with advanced prostate cancer may help improve the pain, anxiety and quality of sleep and life of patients.

The combined effect of triglyceride-glucose index and high-sensitivity C-reactive protein on cardiovascular outcomes in patients with chronic coronary syndrome: A multicenter cohort study.

BACKGROUND: The triglyceride-glucose (TyG) index and high-sensitivity C-reactive protein (hsCRP) are the commonly used biomarkers for insulin resistance and systemic inflammation, respectively. We aimed to investigate the combined association of TyG and hsCRP with the major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). METHODS: A total of 9421 patients with CCS were included in this study. The primary endpoint was defined as a composite of MACE covering all-cause death, nonfatal myocardial infarction, and revascularization. RESULTS: During the 2-year follow-up period, 660 (7.0%) cases of MACE were recorded. Participants were divided equally into three groups according to TyG levels. Compared with the TyG T1 group, the risk of MACE was significantly higher in the TyG T3 group. It is noteworthy that among patients in the highest tertile of TyG, hsCRP >3 mg/L was significantly associated with an increased risk of MACE, whereas the results were not significant in the medium to low TyG groups. When patients were divided into six groups according to hsCRP and TyG, the Cox regression analysis showed that patients in the TyG T3 and hsCRP >3 mg/L group had a significantly higher risk of MACE than those in the TyG T1 and hsCRP ≤3 mg/L group. However, no significant interaction was found between TyG and hsCRP on the risk of MACE. CONCLUSION: Our study suggests that the concurrent assessment of TyG and hsCRP may be valuable in identifying high-risk populations and guiding management strategies among CCS patients.

Prospects of Pseudomonas in Microbial Fuel, Bioremediation, and Sustainability.

Microbial applications in agriculture and industry have gained significant attention due to their potential to address environmental challenges and promote sustainable development. Among these, the genus Pseudomonas stands out as a promising candidate for various biotechnological uses, thanks to its metabolic flexibility, resilience, and adaptability to diverse environments. This review provides a comprehensive overview of the current state and future prospects of microbial fuel production, bioremediation, and sustainable development, focusing on the pivotal role of Pseudomonas species. We emphasize the importance of microbial fuel as a renewable energy source and discuss recent advancements in enhancing biofuel generation using Pseudomonas strains. Additionally, we explore the critical role of Pseudomonas in bioremediation processes, highlighting its ability to degrade a wide spectrum of pollutants, including hydrocarbons, pesticides, and heavy metals, thereby reducing environmental contamination. Despite significant progress, several challenges remain. These include refining microbial strains for optimal process efficiency and addressing ecological considerations. Nonetheless, the diverse capabilities of Pseudomonas offer promising avenues for innovative solutions to pressing environmental issues, supporting the transition to a more sustainable future.

[Spatiotemporal Variation Characteristics and Driving Factors of Cultivated Land NPP in the Shandong Area Around the Bohai Sea].

The Bohai Rim Plain is an important grain-producing area in China. The cultivated land resources have great potential for production, but there are many influencing factors. Understanding the spatiotemporal change characteristics and driving factors of the net primary productivity （NPP） of cultivated land vegetation in this region is of great significance to improve the regional cultivated land production conditions, excavate and enhance the production capacity of cultivated land, and ensure national food security. In this study, Theil-Sen Median trend analysis, Mann-Kendall significance test, Hurst index, and other methods were used to explore the spatiotemporal change characteristics, stability, and sustainability of regional cultivated land NPP. The influence of driving factors on the spatial heterogeneity of cultivated land NPP was analyzed by using optical parameters-based geographical detectors. The results showed that： ① From 2001 to 2019, due to the expansion of construction land during industrialization and urbanization, the cumulative decrease in the area of cultivated land in the Shandong area around the Bohai Sea was 2 004.51 km2. ② During the selected research period, the interannual variation of average cultivated land NPP showed a fluctuating and increasing trend. In terms of spatial distribution, the NPP of cultivated land was bounded by the Dongying District, with the spatial heterogeneity in the north being significantly lower than that in the south. ③ The area with increasing NPP of cultivated land accounted for 88.06% of the total area of cultivated land, mainly with low and medium fluctuations. The NPP of cultivated land will maintain an overall sustained trend of increase across the region in the future. ④ The average annual relative humidity study area had the strongest explanatory power for the spatial variability of NPP in cropland, with a q-value of 0.26, followed by surface soil salinity and subsoil salinity, with q-values greater than 0.2. The interactions between the different drivers all showed either nonlinear enhancement or bifactorial enhancement. The results of this study will help to reveal the characteristics of the changes in cultivated land production capacity and its driving forces in the Bohai Sea region and also provide a theoretical basis for the ecological protection and sustainable development of the region.

Base on photothermal interfacial molecular transfer for efficient biodiesel catalysis via enzyme@cyclodextrin metal-organic frameworks loaded MXene.

Efficient, green and stable catalysis has always been the core concept of enzyme catalysis in industrial processes for manufacturing. Therefore, we construct a new strategy with photothermal interfacial molecular transfer for green and efficient biodiesel catalysis. We encapsulate Candida albicans lipase B (CalB) in a γ-cyclodextrin metal-organic framework (γ-CD-MOF) loading with Ti3C2TX by in situ growth and electrostatic assembly. The γ-CD-MOF not only protects the fragile enzyme, but also enhances the catalytic performance through the synergistic effects of porous adsorption (MOF pore structure) and interfacial enrichment (cyclodextrins host-guest assembly structure) for accelerating substrate transfer (642.6 %). The CalB@γ-CD-MOF/MXene-i activity can be regulated up to 274.6 % by exposure to near-infrared (NIR). Importantly, CalB@γ-CD-MOF/MXene-i achieves 93.3 % biodiesel conversion under NIR and maintained 86.9 % activity after 6 cycles. Meanwhile, the MXene after the CalB@γ-CD-MOF/MXene catalytic cycle can be almost completely recovered. We verify the mechanism of high catalytic activity of γ-CD-MOF and rationalize the mechanism of CD molecular channel by DFT. Therefore, this highly selective enzyme catalytic platform offers new possibilities for green and efficient preparation of bioenergy.

Short photoperiod inhibited gonadal growth and elevated hypothalamic Dio3 expression unrelated to promoter DNA methylation in young Brandt's voles.

Photoperiod, the length of daylight, has a significant impact on the physiological characteristics of seasonal breeding animals, including their somatic and gonadal development. In rodents, expression of deiodinase type II (Dio2) and III (Dio3) in the hypothalamus is crucial for responding to photoperiodic signals. However, research on the photoperiodism of hypothalamic gene expression and the corresponding regulatory mechanism in Brandt's voles living in the Mongolian steppes is limited. In this study, we gradually changed day length patterns to simulate spring (increasing long photoperiod, ILP) and autumn (decreasing short photoperiod, DSP). We compared the somatic and gonadal development of voles born under ILP and DSP and the expression patterns of five reproduction-related genes in the hypothalamus of young voles. The results showed that DSP significantly inhibited somatic and gonadal development in both female and male offspring. Compared with ILP, Dio3 expression was significantly upregulated in the hypothalamus under DSP conditions and remained elevated until postnatal week 8 in both males and females. However, there was no significant difference in the methylation levels of the proximal promoter region of Dio3 between ILP and DSP, suggesting that methylation in the proximal promoter region may not be involved in regulating the expression of Dio3. These findings suggest that hypothalamic expression of Dio3 plays a key role in the photoperiodic regulation of gonadal activity in Brandt's voles. However, it appears that CpGs methylation in the promoter region is not the main mechanism regulating Dio3 expression.

Association and causal impact of TERT genetic variants on peripheral blood leukocyte telomere length and cerebral small vessel disease risk in a Chinese Han population: a mendelian randomization analysis.

BACKGROUND: Previous observational studies have highlighted potential relationships between the telomerase reverse transcriptase (TERT) gene, short leukocyte telomere length (LTL), and cerebrovascular disease. However, it remains to be established as to whether TERT gene variants are associated with an elevated risk of cerebral small vessel disease (CSVD), and whether there is a causal relationship between LTL and CSVD. METHODS: Five TERT single nucleotide polymorphisms (SNPs) were analyzed in 307 CSVD patients and 320 healthy controls in whom LTL values were quantified. Allele models and four genetic models were used to explore the relationship between these SNP genotypes and CSVD risk. A Mendelian randomization analysis of CSVD risk was then performed using LTL-related SNPs and the polygenic risk score (PRS) constructed from these SNPs as genetic instrumental variables to predict the causal relationship between LTL and CSVD risk. RESULTS: Model association analyses identified two SNPs that were significantly associated with CSVD risk. LTL was significantly correlated with age (P < 0.001), and the MR analysis revealed an association between short LTL and an elevated risk of CSVD. PRS-based genetic prediction of short LTLs was also significantly related to an elevated CSVD risk. CONCLUSION: Multiple genetic models and MR results indicate that TERT gene SNPs may be related to an elevated risk of CSVD, and that shorter LTL may be causally linked to such CSVD risk.

One-Pot Total Synthesis of Natural Products Nitramarine, Nitraridine, and Analogues via a Cascade Oxidation/Pictet-Spengler Condensation/Annulation Process.

A cascade oxidation/Pictet-Spengler condensation/annulation process has been developed for the one-pot total synthesis of nitramarine, nitraridine, and their analogues. The procedure proceeded with easily available quinolines and tryptophan derivatives. A simple and metal-free approach, wide substrate scope, and functional group tolerance make it applicable for the synthesis of diverse bioactive nitramarine, nitraridine, and their derivatives. Furthermore, the bioactivity evaluation has identified two promising leading compounds 5d and 5e with potent antitumor proliferative activity against breast cancer cells.

Inducible RPE-specific GPX4 knockout causes oxidative stress and retinal degeneration with features of age-related macular degeneration.

Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. This disease involves oxidative stress burden in the retina leading to death of retinal pigment epithelial (RPE) cells and photoreceptors. The retina is susceptible to oxidative stress, in part due to high metabolic activity and high concentration of polyunsaturated fatty acids that undergo lipid peroxidation chain reactions. Antioxidant enzymes exist in the retina to combat this stress, including glutathione peroxidase 4 (GPX4). GPX4 specifically reduces oxidized lipids, protecting against lipid peroxidation-induced oxidative stress, which is noted in dry AMD. We hypothesize that Gpx4 knockout within the RPE will result in an environment of chronic oxidative stress yielding degeneration akin to AMD. C57BL/6J mice with a floxed Gpx4 gene were mated with Rpe65Cre/ER mice. Offspring containing Rpe65Cre ± alleles and either Gpx4 WT or Gpx4 fl/fl alleles were administered tamoxifen to induce Gpx4 knockout in Gpx4 fl/fl mice. At sequential timepoints, retinal phenotypes were assessed via in vivo imaging utilizing confocal scanning laser ophthalmoscopy and optical coherence tomography (OCT), and visual function was probed by electroretinography. Retinas were studied post-mortem by immunohistochemical analyses, electron microscopy, plastic sectioning, and quantitative polymerase chain reaction and Western analyses. The RPE-specific Gpx4 knockout model was validated via Western analysis indicating diminished GPX4 protein only within the RPE and not the neural retina. Following Gpx4 knockout, RPE cells became dysfunctional and died, with significant cell loss occurring 2 weeks post-knockout. Progressive thinning of the photoreceptor layer followed RPE degeneration and was accompanied by loss of visual function. OCT and light microscopy showed hyperreflective foci and enlarged, pigmented cells in and above the RPE layer. Electron microscopy revealed decreased mitochondrial cristae and loss of basal and apical RPE ultrastructure. Finally, there was increased carboxyethylpyrrole staining, indicating oxidation of docosahexaenoic acid, and increased levels of mRNAs encoding oxidative stress-associated genes in the RPE and photoreceptors. Overall, we show that RPE-localized GPX4 is necessary for the health of the RPE and outer retina, and that knockout recapitulates phenotypes of dry AMD.

"NO" controversy?: A controversial role in insulin signaling of diabetic encephalopathy.

Insulin, a critical hormone in the human body, exerts its effects by binding to insulin receptors and regulating various cellular processes. While nitric oxide (NO) plays an important role in insulin secretion and acts as a mediator in the signal transduction pathway between upstream molecules and downstream effectors, holds a significant position in the downstream signal network of insulin. Researches have shown that the insulin-NO system exhibits a dual regulatory effect within the central nervous system, which is crucial in the regulation of diabetic encephalopathy (DE). Understanding this system holds immense practical importance in comprehending the targets of existing drugs and the development of potential therapeutic interventions. This review extensively examines the characterization of insulin, NO, Nitric oxide synthase (NOS), specific NO pathway, their interconnections, and the mechanisms underlying their regulatory effects in DE, providing a reference for new therapeutic targets of DE.

Epidemic spreading on spatial higher-order network.

Higher-order interactions exist widely in mobile populations and are extremely important in spreading epidemics, such as influenza. However, research on high-order interaction modeling of mobile crowds and the propagation dynamics above is still insufficient. Therefore, this study attempts to model and simulate higher-order interactions among mobile populations and explore their impact on epidemic transmission. This study simulated the spread of the epidemic in a spatial high-order network based on agent-based model modeling. It explored its propagation dynamics and the impact of spatial characteristics on it. Meanwhile, we construct state-specific rate equations based on the uniform mixing assumption for further analysis. We found that hysteresis loops are an inherent feature of high-order networks in this space under specific scenarios. The evolution curve roughly presents three different states with the initial value change, showing different levels of the endemic balance of low, medium, and high, respectively. Similarly, network snapshots and parameter diagrams also indicate these three types of equilibrium states. Populations in space naturally form components of different sizes and isolations, and higher initial seeds generate higher-order interactions in this spatial network, leading to higher infection densities. This phenomenon emphasizes the impact of high-order interactions and high-order infection rates in propagation. In addition, crowd density and movement speed act as protective and inhibitory factors for epidemic transmission, respectively, and depending on the degree of movement weaken or enhance the effect of hysteresis loops.