Multi-layered computational gene networks by engineered tristate logics.

So far, biocomputation strictly follows traditional design principles of digital electronics, which could reach their limits when assembling gene circuits of higher complexity. Here, by creating genetic variants of tristate buffers instead of using conventional logic gates as basic signal processing units, we introduce a tristate-based logic synthesis (TriLoS) framework for resource-efficient design of multi-layered gene networks capable of performing complex Boolean calculus within single-cell populations. This sets the stage for simple, modular, and low-interference mapping of various arithmetic logics of interest and an effectively enlarged engineering space within single cells. We not only construct computational gene networks running full adder and full subtractor operations at a cellular level but also describe a treatment paradigm building on programmable cell-based therapeutics, allowing for adjustable and disease-specific drug secretion logics in vivo. This work could foster the evolution of modern biocomputers to progress toward unexplored applications in precision medicine.

Global, regional, and national time trends in incidence for depressive disorders, from 1990 to 2019: an age-period-cohort analysis for the GBD 2019.

BACKGROUND: Even with advances in primary health care, depressive disorders remain a major global public health problem. We conducted an in-depth analysis of global, regional and national trends in depressive disorders incidence over the past 30 years. METHODS: Data on the incidence of depressive disorders were obtained by sex (female, male, and both), location (204 countries), age (5-84 years), year (1990-2019) from the Global Burden of Disease Study (GBD) 2019. Further, age-period-cohort modeling was used to estimate the net drift, local drift, age, period and cohort effects between 1990 and 2019. RESULTS: In 2019, although the incidence of depressive disorders has increased by 59.3% to 290 million (95% UI: 256, 328), the age-standardized incidence rate has decreased by 2.35% to 3588.25 per 100,000 people (3152.71, 4060.42) compared to 1990. There was an emerging transition of incidences from the young and middle-aged population to the old population. From 1990 to 2019, the net drift of incidence rate ranged from -0.54% (-0.61%, -0.47%) in low-middle Socio-demographic Index (SDI) regions to 0.52% (0.25%, 0.79%) in high SDI regions. Globally, the incidence rate of depressive disorders increases with age, period effects showing a decreasing risk and cohort effects beginning to decline after the 1960s. CONCLUSIONS: Our current findings reflect substantial health disparities and potential priority-setting of depressive disorders incidence in the three dimensions of age, period and cohort across SDI regions, countries. The scope of healthcare to improve the progression of depressive disorders events can be expanded to include males, females of all ages.

Imidazolium-Based Sulfonating Agent to Control the Degree of Sulfonation of Aromatic Polymers and Enable Plastics-to-Electronics Upgrading.

The accumulation of plastic waste in the environment is a growing environmental, economic, and societal challenge. Plastic upgrading, the conversion of low-value polymers to high-value materials, could address this challenge. Among upgrading strategies, the sulfonation of aromatic polymers is a powerful approach to access high-value materials for a range of applications, such as ion-exchange resins and membranes, electronic materials, and pharmaceuticals. While many sulfonation methods have been reported, achieving high degrees of sulfonation while minimizing side reactions that lead to defects in the polymer chains remains challenging. Additionally, sulfonating agents are most often used in large excess, which prevents precise control over the degree of sulfonation of aromatic polymers and their functionality. Herein, we address these challenges using 1,3-disulfonic acid imidazolium chloride ([Dsim]Cl), a sulfonic acid-based ionic liquid, to sulfonate aromatic polymers and upgrade plastic waste to electronic materials. We show that stoichiometric [Dsim]Cl can effectively sulfonate model polystyrene up to 92% in high yields, with minimal defects and high regioselectivity for the para position. Owing to its high reactivity, the use of substoichiometric [Dsim]Cl uniquely allows for precise control over the degree of sulfonation of polystyrene. This approach is also applicable to a wide range of aromatic polymers, including waste plastic. To prove the utility of our approach, samples of poly(styrene sulfonate) (PSS), obtained from either partially sulfonated polystyrene or expanded polystyrene waste, are used as scaffolds for poly(3,4-ethylenedioxythiophene) (PEDOT) to form the ubiquitous conductive material PEDOT:PSS. PEDOT:PSS from plastic waste is subsequently integrated into organic electrochemical transistors (OECTs) or as a hole transport layer (HTL) in a hybrid solar cell and shows the same performance as commercial PEDOT:PSS. This imidazolium-mediated approach to precisely sulfonating aromatic polymers provides a pathway toward upgrading postconsumer plastic waste to high-value electronic materials.

Prevalence and associated factors of adolescent psychological abuse, neglect in Western China a multi-center cross-sectional study.

Background: The western region of China has a dense population, relatively underdeveloped economy, and a significant number of left-behind children. Currently, the prevalence of adolescent psychological abuse, neglect, and the factors associated with these issues in the region remain unclear. This study aims to evaluate the current status of adolescent psychological abuse and neglect and its associated factors in this region.Methods: Data were collected from 50 schools in western China through cluster sampling to target adolescents aged 12 to 18. A comprehensive survey form was used to collect socio-demographic characteristics of adolescents. The Child Psychological Abuse and Neglect Scale was employed to assess the current psychological abuse and neglect of adolescents. Independent samples t-tests were used for inter-group comparisons. A Directed Acyclic Graph was constructed for controlling confounding variables. Subsequently, binary logistic regression analysis was performed, and a nomogram risk factors model was developed using R Studio.Results: This study included 12,743 teenagers, with an average age of 15.53(±1.39) years. Among them, 4,965 individuals, accounting for 39.0%, reported experiences of psychological abuse, while 4,167 individuals, accounting for 32.7%, reported experiences of neglect. The rates of psychological abuse and neglect in adolescents are influenced by gender, grade, left-behind experience, parental marital status, and living on campus (P < .05).Conclusion: Adolescents in western China exhibit higher rates of psychological abuse and neglect compared to those in the eastern and northern regions of China. Gender, grade, left-behind experience, and family factors significantly influence the psychological abuse and neglect of adolescents.

This study is the first large-scale, multi-centre, cross-sectional analysis of psychological abuse and neglect among youth in Western China, a region with relatively underdeveloped economic and social conditions.This article fills in the gap in the region's research on psychological abuse and neglect by addressing the issues of small sample size, limited coverage, and a lack of variables included.This provides a crucial theoretical foundation for enhancing the mental well-being of youth in this region and preventing psychological and mental illnesses among youth.

Time trends in the mortality of testicular cancer across the BRICS: an age-period-cohort analysis for the GBD 2019.

Testicular cancer (TCa) is a rare but impactful malignancy that primarily affects young men. Understanding the mortality rate of TCa is crucial for improving prevention and treatment strategies to reduce the risk of death among patients. We obtained TCa mortality data by place (5 countries), age (20-79 years), and year (1990-2019) from the Global Burden of Disease Study 2019. Age-period-cohort model was used to estimate the net drift, local drift, age effects, period and cohort effects. In 2019, the global mortality of TCa increased to 10842 (95% UI 9961, 11902), with an increase of 50.08% compared to 1990.The all-age mortality rate for TCa in 2019 increased from 0.17/100,000 (95% UI 0.13, 0.20) in China to 0.48/100,000 (95% UI 0.38, 0.59) in Russian Federation, whereas the age-standardized mortality rate in 2019 was highest in the South Africa 0.47/100,000 (95% UI 0.42, 0.53) and lowest in the China 0.16/100,000 (95% UI 0.13, 0.19). China's aging population shifts mortality patterns towards the elderly, while in Russian Federation, young individuals are primarily affected by the distribution of deaths. To address divergent TCa mortality advancements in BRICS countries, we propose a contextually adaptive and resource-conscious approach to prioritize TCa prevention. Tailoring strategies to contextual diversity, including policy frameworks, human resources, and financial capacities, will enhance targeted interventions and effectiveness in reducing TCa mortality.

Photoactivation of Millimeters Thick Liquid Crystal Elastomers with Broadband Visible Light Using Donor-Acceptor Stenhouse Adducts.

Light-responsive liquid crystal elastomers (LCEs) are stimuli-responsive materials that facilitate the conversion of light energy into a mechanical response. In this work, a novel polysiloxane-based LCE with donor-acceptor Stenhouse adduct (DASA) side-chains is synthesized using a late-stage functionalization strategy. It is demonstrated that this approach does not compromise the molecular alignment observed in the traditional Finkelmann method. This easy, single-batch process provides a robust platform to access well-aligned, light-responsive LCE films with thickness ranging from 400 µm to a 14-layer stack that is 5 mm thick. Upon irradiation with low-intensity broadband visible light (100-200 mW cm-2), these systems undergo 2D planar actuation and complete bleaching. Conversely, exposure to higher-intensity visible light induces bending followed by contraction (300 mW cm-2). These processes are repeatable over several cycles. Finally, it is demonstrated how light intensity and the resulting heat generation influences the photothermal stationary state equilibrium of DASA, thereby controlling its photoresponsive properties. This work establishes the groundwork for advancement of LCE-based actuators beyond thin film and UV-light reliant systems.

Titanium Alloy Materials with Very High Cycle Fatigue: A Review.

As the reliability and lifespan requirements of modern equipment continues to escalate, the problems with very high cycle fatigue (VHCF) has obtained increasingly widespread attention, becoming a hot topic in fatigue research. Titanium alloys, which are the most extensively used metal materials in the modern aerospace industry, are particularly prone to VHCF issues. The present study systematically reviewed and summarized the latest (since 2010) developments in VHCF research on titanium alloy, with special focus on the (i) experimental methods, (ii) macroscopic and microscopic characteristics of the fatigue fractures, and (iii) construction of fatigue fracture models. More specifically, the review addresses the technological approaches that were used, mechanisms of fatigue crack initiation, features of the S-N curves and Goodman diagrams, and impact of various factors (such as processing, temperature, and corrosion). In addition, it elucidates the damage mechanisms, evolution, and modeling of VHCF in titanium alloys, thereby improving the understanding of VHCF patterns in titanium alloys and highlighting the current challenges in VHCF research.

Copper(II)-Based Nano-Regulator Correlates Cuproptosis Burst and Sequential Immunogenic Cell Death for Synergistic Cancer Immunotherapy.

Immunogenic cell death (ICD) of tumor cells serves as a crucial initial signal in the activation of anti-tumor immune responses, holding marked promise in the field of tumor immunotherapy. However, low immunogenicity tumors pose challenges in achieving complete induction of ICD, thereby limiting the response rates of immunotherapy in clinical patients. The emergence of cuproptosis as a new form of regulated cell death has presented a promising strategy for enhanced immunotherapy of low immunogenic tumors. To trigger cuproptosis, copper-ionophore elesclomol (ES) had to be employed for the copper-transporting-mediated process. Herein, we proposed a copper(II)-based metal-organic framework nanoplatform (Cu-MOF) to facilitate a cooperative delivery of encapsulated ES and copper (ES-Cu-MOF) to induce cuproptosis burst and enhance ICD of fibrosarcoma. Our results showed that the ES-Cu-MOF nano-regulator could effectively release Cu2+ and ES in response to the intracellular environment, resulting in elevated mitochondrial ROS generation and initiated cuproptosis of tumor cells. Furthermore, sequential ICDs were significantly triggered via the ES-Cu-MOF nano-regulator to activate the anti-tumor immune response. The results of tumor inhibition experiment indicated that the nano-regulator of ES-Cu-MOF obviously accumulated in the tumor site, inducing ICD for dendritic cell activation. This enabled an increased infiltration of cytotoxic CD8+ T cells and consequently enhanced antitumor immune responses for successfully suppressing fibrosarcoma growth. Thus, the copper(II)-based metal-organic framework nano-regulator offered a promising approach for inducing cuproptosis and cuproptosis-stimulated ICD for cancer immunotherapy.

The relationship between health behaviors and quality of life: the mediating roles of activities of daily living and psychological distress.

Objective: The aim of this study is to examine the role of activities of daily living performance (ADLs) and psychological distress in mediating the process by which health behaviors affect QOL. Methods: A non-probabilistic study was conducted among 1,065 older adult people older than 60 years. Participants were assessed using the Barthel Index, Functional Activities Questionnaire (FAQ), Kessler Psychological Distress Scale (K10), Australian Active Survey, and EQ-VAS score. The SPSS22.0 software was used to analyze the differences in QOL scores among older adults with different demographic characteristics. Pearson correlation analysis was used to analyze the correlation between health behaviors, psychological distress, ADLs, and QOL. Amos23.0 software was used to construct structural equation model (SEM) to analyze the path of health behavior affecting QOL and the mediating role of BADLs, IADLs and psychological distress. Results: (1) The direct effect of health behaviors on QOL was not significant in the model; (2) ADLs had multiple mediating effects on the relationship between health behaviors and QOL, and the incidence of ADL limitation was negatively correlated with the reported QOL in the older adult; (3) Psychological distress had a significant mediating effect on the relationship between health behaviors and QOL. Conclusion: The results of this study elucidated the mechanisms of the correlation between health behaviors and QOL, and added to the existing literature. In addition, these mediating factors and indirect pathways have been identified as targets for intervention to improve the QOL of older adult individuals, which is important for achieving healthy aging.

Isorhamnetin alleviates ferroptosis-mediated colitis by activating the NRF2/HO-1 pathway and chelating iron.

Ferroptosis of intestinal epithelial cells (IECs) had been identified as a key factor in the development of ulcerative colitis (UC). Therefore, targeted inhibition of ferroptosis may provide a new strategy for the treatment of UC. Isorhamnetin (ISO) was an O-methylated flavonol with therapeutic effects on a variety of diseases, such as cardiovascular disease, neurological disorders and tumors. However, the role and mechanism of ISO in ferroptosis and associated colitis were rarely investigated. In this study, we demonstrated that ISO could effectively alleviate intestinal inflammation by inhibiting ferroptosis of IECs in DSS-induced mice. Moreover, our results shown that ISO acted as a potent and common ferroptosis inhibitor in multiple human and murine cell lines. Mechanistically, ISO inhibited ferroptosis independent of its previously reported targets MEK1 and PI3K, but alleviated oxidative stress by targeting and activating NRF2. Furthermore, ISO could also directly chelate iron to hinder ferroptosis. In conclusion, our study indicated that ISO as a novel potential ferroptosis inhibitor, providing a promising therapeutic strategy for ferroptosis-related colitis.

Identification of odorant-binding proteins and functional analysis of antenna-specific BhorOBP28 in Batocera horsfieldi (Hope).

BACKGROUND: The important wood-boring pest Batocera horsfieldi has evolved a sensitive olfactory system to locate host plants. Odorant-binding proteins (OBPs) are thought to play key roles in olfactory recognition. Therefore, exploring the physiological function of OBPs could facilitate a better understanding of insect chemical communications. RESULTS: In this research, 36 BhorOBPs genes were identified via transcriptome sequencing of adults' antennae from B. horsfieldi, and most BhorOBPs were predominantly expressed in chemosensory body parts. Through fluorescence competitive binding and fluorescence quenching assays, the antenna-specific BhorOBP28 was investigated and displayed strong binding affinities forming stable complexes with five volatiles, including (+)-α-Pinene, (+)-Limonene, ß-Pinene, (-)-Limonene, and (+)-Longifolene, which could also elicit conformation changes when they were interacting with BhorOBP28. Batocera horsfieldi females exhibited a preference for (-)-Limonene, and a repellent response to (+)-Longifolene. Feeding dsOBP19 produced by a bacteria-expressed system with a newly constructed vector could lead to the knockdown of BhorOBP28, and could further impair B. horsfieldi attraction to (-)-Limonene and repellent activity of (+)-Longifolene. The analysis of site-directed mutagenesis revealed that Leu7, Leu72, and Phe121 play a vital role in selectively binding properties of BhorOBP28. CONCLUSION: By modeling the molecular mechanism of olfactory recognition, these results demonstrate that BhorOBP28 is involved in the chemoreception of B. horsfieldi. The bacterial-expressed dsRNA delivery system gains new insights into potential population management strategies. Through the olfactory process concluded that discovering novel behavioral regulation and environmentally friendly control options for B. horsfieldi in the future. © 2024 Society of Chemical Industry.

Influence of Controlled Chirality on the Crystallization of Maleimide-Functionalized 3,4-Ethylenedioxythiophene (EDOT-MA) Monomers.

Conjugated poly(alkoxythiophenes) such as poly(3,4-ethylenedioxythiophene) (PEDOT) have attracted considerable interest for use in a variety of applications such as biomedical devices, energy storage, and chemical sensing. Functionalized versions of the 3,4-ethylenedioxythiophene (EDOT) monomer make it possible to create polymers with properties tailored for specific applications. The maleimide functional group shows particular promise due to the wide variety of chemical modifications that it can undergo. Here, we examine the role that control of the chirality of the maleimide (MA) substituent has on the crystal structure and crystallization of the EDOT-MA monomer. We describe a method for the synthesis of a homochiral (S) variant of EDOT-MA and compare its crystallography, morphology, and thermal properties to that of the (R,S) EDOT-MA racemic compound. The conformation of the EDOT-MA molecule was substantially different, with the molecules adopting an "L" shape in the homochiral crystal, while in the racemic crystals, they were more colinear. The thermal stability of the homochiral crystals (Tm = 128.6 °C) was slightly higher than the racemic ones (Tm = 102.8 °C). We expect these results to be important in better understanding the solid-state assembly of the corresponding polymers prepared from these monomers.

Cost-Effectiveness Analysis of Fluocinolone Acetonide Intravitreal (FAI) Implant for Chronic Noninfectious Uveitis Affecting the Posterior Segment of the Eye (NIU-PS) in China.

INTRODUCTION: Chronic non-infectious uveitis affecting the posterior segment (NIU-PS), which can be recurrent and persistent for numerous years, mainly affects people of working age and significantly increases the risk of visual impairment. This study aimed to investigate the cost-effectiveness of fluocinolone acetonide intravitreal (FAI) implant in the treatment of patients with chronic NIU-PS from the Chinese healthcare perspective. METHODS: A Markov model with a 2-week cycle was constructed from the perspective of the Chinese healthcare system over a lifetime time horizon. The model consists of four health states: on-treatment, treatment failure, blindness, and death. The outcomes for effectiveness were based on the Chinese real-world study (RWS). Utilities and mortality rates were derived from published literature and standard sources. Costs were determined from the MENET website, prices of medical service items at local providers, published literature, and expert surveys. Outcomes were measured in quality-adjusted life years (QALYs). Sensitivity analyses were performed to account for the impact of uncertainty. RESULTS: It was estimated that in the base case, the FAI implant provided 0.43 incremental QALYs compared with the limited current practice (LCP) at an additional cost of $7503.72 (¥50,575.05), resulting in an incremental cost-effectiveness ratio (ICER) of $17,373.49 (¥117,097.33) per QALY gained. Parameters related to utility emerged as the primary influencers on the outcomes. In probabilistic sensitivity analysis (PSA), considering the willingness-to-pay (WTP) threshold of $19,072 (¥128,547) and $38,145 (¥257,094), the FAI implant had 67.70% and 99.50% probability of being cost-effective, respectively. As demonstrated in the scenario analysis, if the FAI implant aligns its price reduction with the average rate from the 2023 negotiation of the National Reimbursement Drug List (NRDL), it would result in lower costs and represent an absolute advantage. CONCLUSIONS: The FAI implant, which can effectively reduce the recurrence rate and maintain the incremental costs within the WTP limit, is likely to be cost-effective in treating chronic NIU-PS in China.

Childhood environmental unpredictability and hoarding: Mediating roles of attachment and security.

Life history theory provides a unified perspective for understanding human behaviors as adaptive strategies to specific environmental conditions. Within this theoretical framework, hoarding emerges as a behavior reflecting an evolved strategy in response to unpredictable environmental challenges, serving as a buffer against resource scarcity and enhancing survival prospects. This study aimed to explore the key roles of childhood environmental unpredictability, attachment, and sense of security in the development of hoarding. 662 participants completed scales on childhood environmental unpredictability, Revised Experiences in Close Relationships (ECR-R), sense of insecurity, and Savings Inventory-Revised (SI-R). The results showed that childhood environmental unpredictability was significantly positively correlated with hoarding. Attachment anxiety and sense of security individually mediate the effect of childhood environmental unpredictability on hoarding. Additionally, 'attachment anxiety--sense of security' and 'attachment avoidance--sense of security' serve as chain mediators in this relationship separately. This study offers insights into the cognitive-behavioral model of hoarding, highlighting the importance of life history theory in examining childhood environmental unpredictability's relationship with hoarding. It also integrates insights from the psychosocial acceleration theory into our comprehension of hoarding's development. Future research directions are also discussed.

Variations in species diversity patterns and community assembly rules among vegetation types in the karst landscape.

The various vegetation types in the karst landscape have been considered the results of heterogeneous habitats. However, the lack of a comprehensive understanding of regional biodiversity patterns and the underlying ecological processes limits further research on ecological management. This study established forest dynamic plots (FDPs) of the dominant vegetation types (shrubland, SL; mixed tree and shrub forest, MTSF; coniferous forest, CF; coniferous broadleaf mixed forest, CBMF; and broadleaf forest, BF) in the karst landscape and quantified the species diversity patterns and potential ecological processes. The results showed that in terms of diversity patterns, the evenness and species richness of the CF community were significantly lower than other vegetation types, while the BF community had the highest species richness. The other three vegetation types showed no significant variation in species richness and evenness. However, when controlling the number of individuals of FDPs, the rarefied species richness showed significant differences and ranked as BF > SL > MTSF > CBMF > CF, highlighting the importance of considering the impacts of abundance. Additionally, the community assembly of climax communities (CF or BF) was dominated by stochastic processes such as species dispersal or species formation, whereas deterministic processes (habitat filtering) dominated the secondary forests (SL, MTSF, and CBMF). These findings proved that community assembly differs mainly between the climax community and other communities. Hence, it is crucial to consider the biodiversity and of the potential underlying ecological processes together when studying regional ecology and management, particularly in heterogeneous ecosystems.

How do species richness and its component dependence vary along the natural restoration in extremely heterogeneous forest ecosystems?

Giant habitat heterogeneity is an important factor contributing to the high species richness (SR) in karst forests. Yet, the driving factor behind the alterations in SR patterns during natural restoration remains unclear. In this study, we established the forest dynamics plots along the natural restoration sequence (including shrub-tree mixed forest stage (SC), secondary forest stage (SG) and old-growth forest sage (OG)) in degraded karst forests to compare the SR and the dependence on its components (including total community abundance, species abundance distribution (SAD), and conspecific spatial aggregation (CSA)) among stages of natural restoration. By evaluating the degree of contribution of the components to local SR and rarefied SR, we found that the SG exhibited the highest local SR, while the rarefied SR remained increasing along the restoration sequence after controlling the sample size. At SC-SG stage, SAD and CSA contributed negatively to the differences in SR, while abundance made a positive contribution to SR differences. At SG-OG, abundance contributed positively to the difference in SR at all scales, while SAD contributed negatively at small scales. No significant contribution of CSA was found at observed scales. In addition, local SR varied more significantly with PIE than with abundance. Our research emphasizes the importance of eliminating the influence of abundance on species richness in forest ecology and management, as well as the significance of separately evaluating the components that shape the diversity patterns.

One Pot Photomediated Formation of Electrically Conductive Hydrogels.

Electrically conductive hydrogels represent an innovative platform for the development of bioelectronic devices. While photolithography technologies have enabled the fabrication of complex architectures with high resolution, photoprinting conductive hydrogels is still a challenging task because the conductive polymer absorbs light which can outcompete photopolymerization of the insulating scaffold. In this study, we introduce an approach to synthesizing conductive hydrogels in one step. Our approach combines the simultaneous photo-cross-linking of a polymeric scaffold and the polymerization of 3,4-ethylene dioxythiophene (EDOT), without additional photocatalysts. This process involves the copolymerization of photo-cross-linkable coumarin-containing monomers with sodium styrenesulfonate to produce a water-soluble poly(styrenesulfonate-co-coumarin acrylate) (P(SS-co-CoumAc)) copolymer. Our findings reveal that optimizing the [SS]:[CoumAc] ratio at 100:5 results in hydrogels with the strain at break up to 16%. This mechanical resilience is coupled with an electronic conductivity of 9.2 S m-1 suitable for wearable electronics. Furthermore, the conductive hydrogels can be photopatterned to achieve micrometer-sized structures with high resolution. The photo-cross-linked hydrogels are used as electrodes to record stable and reliable surface electromyography (sEMG) signals. These novel photo-cross-linkable polymers combined with one-pot PEDOT (poly-EDOT) polymerization open possibilities for rapidly prototyping complex bioelectronic devices and creating custom-designed interfaces between electronics and biological systems.

Deficiency of ASGR1 Alleviates Diet-Induced Systemic Insulin Resistance via Improved Hepatic Insulin Sensitivity.

BACKGRUOUND: Insulin resistance (IR) is the key pathological basis of many metabolic disorders. Lack of asialoglycoprotein receptor 1 (ASGR1) decreased the serum lipid levels and reduced the risk of coronary artery disease. However, whether ASGR1 also participates in the regulatory network of insulin sensitivity and glucose metabolism remains unknown. METHODS: The constructed ASGR1 knockout mice and ASGR1-/- HepG2 cell lines were used to establish the animal model of metabolic syndrome and the IR cell model by high-fat diet (HFD) or drug induction, respectively. Then we evaluated the glucose metabolism and insulin signaling in vivo and in vitro. RESULTS: ASGR1 deficiency ameliorated systemic IR in mice fed with HFD, evidenced by improved insulin intolerance, serum insulin, and homeostasis model assessment of IR index, mainly contributed from increased insulin signaling in the liver, but not in muscle or adipose tissues. Meanwhile, the insulin signal transduction was significantly enhanced in ASGR1-/- HepG2 cells. By transcriptome analyses and comparison, those differentially expressed genes between ASGR1 null and wild type were enriched in the insulin signal pathway, particularly in phosphoinositide 3-kinase-AKT signaling. Notably, ASGR1 deficiency significantly reduced hepatic gluconeogenesis and glycogenolysis. CONCLUSION: The ASGR1 deficiency was consequentially linked with improved hepatic insulin sensitivity under metabolic stress, hepatic IR was the core factor of systemic IR, and overcoming hepatic IR significantly relieved the systemic IR. It suggests that ASGR1 is a potential intervention target for improving systemic IR in metabolic disorders.

The mediating role of impulsivity between sleep quality and suicidal ideation in adolescent population: a multicenter cross-sectional study in the northeastern Sichuan, China.

Introduction: Suicidal ideation is a critical early stage in the progression towards suicidal be havior. Prior research has established links between sleep quality, impulsivity, and suicidal tendencies, yet the interaction among these factors has been less explored. This study aims to explore the mediating role of impulsivity in the relationship between sleep quality and suicidal ideation in adolescents. Methods: Employing a cross-sectional study design, 6,974 questionnaires were distributed,including the Socio-demographic Characteristics Questionnaire, Barratt Impulsiveness Scale, the Positive and Negative Suicide Ideation Inventory,and the Pittsburgh Sleep Quality Index Scale. The participants were high school and middle school students from 33 schools in northeastern Sichuan, China, selected through random cluster sampling. Results: Of these 6,786 questionnaires were analyzed. The participant distribution included 47.2% male and 52.8% female students, with 68.3% from junior schools and 31.7% from senior schools. The prevalence of suicidal ideation was found to be 13.6%. The analysis, which involved correlation analysis and the construction of a structural equation model, revealed that sleep quality had a significant positive effect on impulsivity (ß:0.289,p < 0.05), and impulsivity, in turn, had a positive impact on suicidal ideation (ß:0.355,p < 0.05).Moreover, sleep quality was directly linked to suicidal ideation (ß:0.208,p < 0.05). Thus, sleep quality affects suicidal ideation both directly and indirectly through impulsivity. Discussion: The results of this study suggest that both sleep quality and impulsivity are significant direct influencers of suicidal ideation among adolescents in the region studied, with impulsivity also playing an indirect role in the relationship between sleep quality and suicidal ideation.

Effect of electrolytic zero-valent iron activated sodium hypochlorite on sludge dewatering performance.

Using electrolytic zero-valent iron-activated sodium hypochlorite (EZVI-NaClO) to pretreat sludge, the capillary suction time (CST) was utilized to evaluate sludge dewaterability. Ammonia nitrogen (NH4-N), dissolved phosphorus, and total phosphorus in the supernatant were used to analyze sludge disintegration. This approach aimed to evaluate the effectiveness of the pretreatment process and its impact on the sludge composition. The migration and transformation of extracellular polymeric substances (EPS), including dissolved EPS (S-EPS), loosely boundEPS, and tightly bound-EPS (TB-EPS), were analyzed by detecting protein and polysaccharide concentrations and three-dimensional fluorescence excitation-emission spectroscopy (3D-EEM). The sludge particle properties, including sludge viscosity and particle size, were also analyzed. The results suggested that the optimal pH value, NaClO dosage, current, and reaction time were 2, 100 mg/gDS (dry sludge), 0.2A, and 30 min, respectively, with a CST reduction of 43%. Protein and polysaccharide contents in TB-EPS were significantly reduced in the EZVI-NaClO group. Conversely, protein and polysaccharides contents in S-EPS increased, suggesting that EZVI-NaClO treatment could disrupt the EPS. Besides, the viscosity of the treated sludge decreased from 195.4 to 54.9 mPa·S, indicating that sludge fluidity became better. ZEVI-NaClO could enhance sludge dewaterability by destructing protein and polysaccharide structure and improving sludge hydrophobicity.