The application of graphene oxide and ferroptosis in the diagnosis and treatment of colorectal cancer: a narrative review.

Background and Objective: Colorectal cancer (CRC), a leading global malignancy, continues to challenge the medical community. Despite advancements in surgical, chemotherapeutic, radiation, targeted, and immunotherapeutic strategies, issues like resistance and side effects persist. This review illuminates the potential of ferroptosis, an emerging non-apoptotic cell death form, and graphene oxide (GO), with its distinctive physicochemical properties, in CRC therapy. Methods: The databases search included PubMed, Medline and Web of Science. Search terms focused on CRC, graphene, GO, ferroptosis, and related aspects in therapy and drug delivery. The time frame for literature retrieval was up to April 2024. Studies in languages other than English were excluded. Key Content and Findings: Ferroptosis has been recognized for its role in addressing treatment resistance, a notable hurdle in effective CRC management. This form of cell death offers a promising avenue for enhancing the effectiveness of existing treatments. However, understanding its mechanisms and clinical implications in CRC remains an area of active research, with significant progress required for its practical application. Simultaneously, GO, a versatile two-dimensional material, has demonstrated substantial potential in biomedical applications, especially in cancer therapy. Its high specific surface area and unique π-electron domains facilitate the effective binding of chemotherapy drugs, target genes, and photosensitizers. This makes GO a promising candidate in cancer diagnosis and treatment, particularly through tumor photothermal and photodynamic therapy (PDT). Despite these advancements, GO's clinical application faces challenges, including in vitro cytotoxicity and decreased biodegradability, necessitating further research. Conclusions: This review focuses on the characteristics of GO and ferroptosis, as well as their applications in tumor diagnosis and treatment, with a particular emphasis on their potential in CRC.

Advancing necrotizing enterocolitis prediction through iterative monitoring.

Background: Necrotizing enterocolitis (NEC) is a severe inflammatory intestinal disease in preterm infants, marked by heightened morbidity and mortality. Timely prediction of NEC is significant in the management of critical neonates. However, it is difficult to predict NEC accurately because of the multi-factorial pathogenesis. This study aimed to develop a prediction model through repeated measurement data to further improve the accuracy of prediction in NEC. Methods: We retrospectively collected clinical data of premature infants admitted to the Neonatology Department of the First Affiliated Hospital of Anhui Medical University from January 2016 to December 2023. The infants were categorized into the NEC group (Bell's stage ≥ II) (n=150) and the non-NEC group (n=150). The clinical baseline data of the NEC and non-NEC groups were matched. Laboratory examination indicators were collected on the 1st day, the 7th day after birth, and the day of NEC onset. Univariate and multivariate logistic regression analyses were conducted to identify independent factors influencing NEC. A nomogram was constructed based on these factors to predict NEC. The concordance index and calibration plot were used to assess the efficiency of the nomogram in the training and validation cohorts. Results: This study demonstrated that antenatal steroids, antenatal antibiotics, probiotics treatment before NEC, anion gap (AG, day 7), and mean corpuscular volume (MCV, day 7) were independent risk factors which combined to accurately predict NEC. A nomogram of NEC was created utilizing these five predictors. With an area under the receiver operator characteristic (ROC) curve of 0.835 [95% confidence interval (CI): 0.785-0.884]. Concordance index for the training and validation groups were 0.835 and 0.848, respectively. As the calibration plots indicate, the predicted probability of NEC is highly consistent with the actual observation. Conclusions: The risk estimation nomogram for NEC offers clinical value by guiding early prediction, targeted prevention, and early intervention strategies for NEC.

Improving staff wellness via an after-hours healthy sustainable meals program: A general surgery residency pilot.

Healthcare worker wellness is foundational to delivering quality care. Yet, healthcare facilities often lack access to healthy and sustainable food overnight and on weekends. Healthy, low-carbon meals were provided free of charge after hours to on-call General Surgery residents at the University of British Columbia and the impact on resident well-being assessed using pre- and post-intervention surveys. Financial and time stress reduced significantly with the provision of meals (P's < .01), while emotional and physical stress levels did not change. Average meal expenses decreased from $33 to $10 (P < .001). Increasing food access on call is an impactful intervention to improve resident health and well-being.

Evaluating Patient Experience with Food in a Hospital-Wide Survey.

Purpose: Patient dissatisfaction with hospital food is an important driver of poor food intake in hospitals. The objective of this study was to examine patient satisfaction with current menu offerings and explore patient preferences and values, in order to inform a patient-centred menu redesign.Methods: Between July and September 2021, a cross-sectional survey was distributed to inpatients receiving a lunch tray at Vancouver General Hospital, a large tertiary care centre in Vancouver, Canada. The survey was based on the Acute Care Hospital Foodservice Patient Satisfaction Questionnaire, with additional questions on food experience, factors impacting preferences for hospital meals, interest in plant-rich diets, and demographics.Results: The response rate was 5.5%, with 271 patients completing at least part of the survey. On a 5-point Likert scale, (5 - highest score; 1 - lowest score) satisfaction with food quality (mean = 3.09, p < 0.001) and the overall experience (mean = 3.54, p < 0.001) was lower than industry benchmark of 4, and qualitative feedback was generally negative. Open-ended responses indicated patients were interested in expanded cultural diversity in food provision, more fresh produce and better flavours, and were generally open to trying plant-rich foods.Conclusions: A number of opportunities for improvement were identified in this survey, which will inform an upcoming menu redesign in this institution.

Regulation of YAP translocation by myeloid Pten deficiency alleviates acute lung injury via inhibition of oxidative stress and inflammation.

BACKGROUND: Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is intricately involved in modulating the inflammatory response in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Nevertheless, the myeloid PTEN governing Hippo-YAP pathway mediated oxidative stress and inflammation in lipopolysaccharide (LPS)-induced ALI remains to be elucidate. METHODS: The floxed Pten (PtenFL/FL) and myeloid-specific Pten knockout (PtenM-KO) mice were intratracheal instill LPS (5 mg/kg) to establish ALI, then Yap siRNA mix with the mannose-conjugated polymers was used to knockdown endogenous macrophage YAP in some PtenM-KO mice before LPS challenged. The bone marrow-derived macrophages (BMMs) from PtenFL/FL and PtenM-KO mice were obtained, and BMMs were transfected with CRISPR/Cas9-mediated glycogen synthase kinase 3 Beta (GSK3ß) knockout (KO) or Yes-associated protein (YAP) KO vector subjected to LPS (100 ng/ml) challenged or then cocultured with MLE12 cells. RESULTS: Here, our findings demonstrate that myeloid-specific PTEN deficiency exerts a protective against LPS-induced oxidative stress and inflammation dysregulated in ALI model. Moreover, ablation of the PTEN-YAP axis in macrophages results in reduced nuclear factor-E2-related factor-2 (NRF2) expression, a decrease in antioxidant gene expression, augmented levels of free radicals, lipid and protein peroxidation, heightened generation of pro-inflammatory cytokines, ultimately leading to increased apoptosis in MLE12 cells. Mechanistically, it is noteworthy that the deletion of myeloid PTEN promotes YAP translocation and regulates NRF2 expression, alleviating LPS-induced ALI via the inhibition of GSK3ß and MST1 binding. CONCLUSIONS: Our study underscores the crucial role of the myeloid PTEN-YAP-NRF2 axis in governing oxidative stress and inflammation dysregulated in ALI, indicating its potential as a therapeutic target for ALI.

Precise antibiotic delivery to the lung infection microenvironment boosts the treatment of pneumonia with decreased gut dysbiosis.

Bacterial pneumonia is a common disease with significant health risks. However, the overuse antibiotics in clinics face challenges such as inadequate targeting and limited drug utilization, leading to drug resistance and gut dysbiosis. Herein, a dual-responsive lung inflammatory tissue targeted nanoparticle (LITTN), designed for targeting lung tissue and bacteria, is screened from a series of prepared nanoparticles consisting of permanent cationic lipids, acid-responsive lipids, and reactive oxygen species-responsive and phenylboronic acid-modified lipids with different surface properties. Such nanoparticle is further verified to enhance the adsorption of vitronectin in serum. Additionally, the optimized nanoparticle exhibits more positive charge and coordination of boric acid with cis-diol in the infected microenvironment, facilitating electrostatic interactions with bacteria and biofilm penetration. Importantly, the antibacterial efficiency of dual-responsive rifampicin-loaded LITTN (Rif@LITTN) against methicillin-resistant staphylococcus aureus is 10 times higher than that of free rifampicin. In a mouse model of bacterial pneumonia, the intravenous administration of Rif@LITTN could precisely target the lungs, localize in the lung infection microenvironment, and trigger the responsive release of rifampicin, thereby effectively alleviating lung inflammation and reducing damage. Notably, the targeted delivery of rifampicin helps protect against antibiotic-induced changes in the gut microbiota. This study establishes a new strategy for precise delivery to the lung-infected microenvironment, promoting treatment efficacy while minimizing the impact on gut microbiota. STATEMENT OF SIGNIFICANCE: Intravenous antibiotics play a critical role in clinical care, particularly for severe bacterial pneumonia. However, the inability of antibiotics to reach target tissues causes serious side effects, including liver and kidney damage and intestinal dysbiosis. Therefore, achieving precise delivery of antibiotics is of great significance. In this study, we developed a novel lung inflammatory tissue-targeted nanoparticle that could target lung tissue after intravenous administration and then target the inflammatory microenvironment to trigger dual-responsive antibiotics release to synergistically treat pneumonia while maintaining the balance of gut microbiota and reducing the adverse effects of antibiotics. This study provides new ideas for targeted drug delivery and reference for clinical treatment of pneumonia.

Advances in understanding and mitigating Atrazine's environmental and health impact: A comprehensive review.

Atrazine is a widely used herbicide in agriculture, and it has garnered significant attention because of its potential risks to the environment and human health. The extensive utilization of atrazine, alongside its persistence in water and soil, underscores the critical need to develop safe and efficient removal strategies. This comprehensive review aims to spotlight atrazine's potential impact on ecosystems and public health, particularly its enduring presence in soil, water, and plants. As a known toxic endocrine disruptor, atrazine poses environmental and health risks. The review navigates through innovative removal techniques across soil and water environments, elucidating microbial degradation, phytoremediation, and advanced methodologies such as electrokinetic-assisted phytoremediation (EKPR) and photocatalysis. The review notably emphasizes the complex process of atrazine degradation and ongoing scientific efforts to address this, recognizing its potential risks to both the environment and human health.

Audience segmentation approach to conservation messaging for transforming the exotic pet trade.

Advancing transformative change for sustainability requires population-wide behavior change. Yet, many behavioral interventions tackling environmental problems only examine average effects on the aggregate, overlooking the heterogeneous effects in a population. We developed and preregistered a novel audience segmentation approach to test the diverse impact of conservation messaging on reducing demand for exotic pets (private action - i.e., desire to own exotic pets or visit wildlife entertainment places) and fostering citizen engagement for system-wide change (civic action - e.g., signing a petition or participating in a protest against the exotic pet trade). Through an online survey with US participants (n = 2953), we identified 4 population segments (early adopters, early majority, late majority, and laggards), representing varying levels of commitment to wildlife conservation and then randomly assigned each segment to one of 3 messaging conditions. Messages highlighting negative consequences of the exotic pet trade and the power of collective action for system change effectively promoted private action among all segments except early adopters (ηp 2 = 0.005). Among civic actions, only the collective action message motivated early adopters and the early majority to sign petitions (φC = 0.193 and φC = 0.097, respectively). Furthermore, the 4 segments showed distinct reasoning for action and inaction on wildlife conservation, with certain relational values, such as care, serving as both motivations and barriers to action. These findings highlight the need for targeted behavioral interventions across diverse populations.

Estrategia de segmentación del público en los mensajes de conservación para transformar el mercado de mascotas exóticas Resumen El progreso en el cambio transformativo para la sustentabilidad requiere de cambios conductuales a nivel poblacional. Sin embargo, muchas intervenciones conductuales que abordan los problemas ambientales sólo analizan los efectos promedio sobre el agregado, lo que ignora los efectos heterogéneos sobre la población. Desarrollamos y preinscribimos una estrategia novedosa de segmentación del público para evaluar los diversos impactos de los mensajes de conservación sobre la reducción de la demanda de mascotas exóticas (acción privada [es decir, el deseo de poseer mascotas exóticas o visitar sitios de entretenimiento con fauna] y promover la participación ciudadana para un cambio sistémico [por ejemplo, firmar una petición o participar en una protesta contra el mercado de mascotas exóticas]). Realizamos una encuesta en línea con participantes estadunidenses (n = 2953) para identificar cuatro segmentos de la población (adoptadores tempranos, mayoría temprana, mayoría tardía y rezagados), los cuales representan diferentes niveles de compromiso con la conservación de fauna, y después le asignamos aleatoriamente a cada segmento una de las siguientes condiciones de mensaje: las consecuencias negativas del mercado de mascotas exóticas, el poder de la acción colectiva para el cambio sistémico e información neutral como control. Los mensajes que resaltaban las consecuencias negativas del mercado de mascotas exóticas y el poder de la acción colectiva promovieron de forma eficiente la acción privada en todos los segmentos excepto los adoptadores tempranos (ηp 2 = 0.005). Entre las acciones cívicas, sólo el mensaje de acción colectiva motivó a los adoptadores tempranos y a la mayoría temprana a firmar peticiones (φC = 0.193 y φC = 0.097, respectivamente). Además, los cuatro segmentos mostraron un razonamiento distinto para la acción e inacción para la conservación de fauna, con ciertos valores de relación, como el cuidado, fungiendo como motivación o barreras para la acción. Estos resultados enfatizan la necesidad de tener intervenciones conductuales focalizadas entre las diferentes poblaciones.

[Research progress on the neural mechanism of the regulation of social isolation on innate behaviors].

Innate behavior is mainly controlled by genetics, but is also regulated by social experiences such as social isolation. Studies in animal models such as Drosophila and mice have found that social isolation can regulate innate behaviors through the changes at the molecular level, such as hormone, neurotransmitter, neuropeptide level, and at the level of neural circuits. In this review, we summarized the research progress on the regulation of social isolation on various animal innate behaviors, such as sleep, reproduction and aggression by altering the expression of conserved neuropeptides and neurotransmitters, hoping to deepen the understanding of the key and conserved signal pathways that regulate innate behavior by social isolation.

[Identification and expression profiling of SAPK gene family members in Dendrobium officinale].

To investigate the potential roles of stress-activated protein kinase (SAPK) gene family members in Dendrobium officinale, we employed multiple bioinformatics methods to identify the members of this family. The physicochemical properties, chromosomal localization, phylogenetic relationship, gene structure, and cis-acting elements of each D. officinale SAPK (DoSAPK) member were analyzed. In addition, their expression profiles in different tissues and under the low-temperature or salt stress treatment were determined by real-time fluorescence quantitative PCR. The results showed that D. officinale carried eight DoSAPK family members, which belonged to three groups (groups Ⅰ, Ⅱ, and Ⅲ). These genes were located on seven chromosomes, and there were two pairs of genes with replication. The DoSAPK members within the same group had similar gene structures, conserved motifs, and secondary structures. The cis-acting elements in the promoter regions of DoSAPK genes included abundant hormone and stress response elements. DoSAPK family members presented tissue-specific expression in D. officinale. Furthermore, they were differentially expressed under the low-temperature or salt stress treatment, which suggested that they might be involved in the responses to low-temperature and salt stress. Intriguingly, DoSAPK1 might play a role in the abiotic stress responses. The results laid a foundation for in-depth study of the members and roles of the DoSAPK gene family.

Naodesheng decoction regulating vascular function via G-protein-coupled receptors: network analysis and experimental investigations.

Introduction: Ischemic stroke (IS) is a detrimental neurological disease with limited treatment options. Recanalization of blocked blood vessels and restoring blood supply to ischemic brain tissue are crucial for post-stroke rehabilitation. The decoction Naodesheng (NDS) composed of five Chinese botanical drugs, including Panax notoginseng (Burk.) F. H. Chen, Ligusticum chuanxiong Hort., Carthamus tinctorius L., Pueraria lobata (Willd.) Ohwi, and Crataegus pinnatifida Bge., is a blood-activating and stasis-removing herbal medicine commonly used for the clinical treatment of cerebrovascular diseases in China. However, the material basis of NDS on the effects of blood circulation improvement and vascular tone regulation remains unclear. Methods: A database comprising 777 chemical metabolites of NDS was constructed. Then, the interactions between various herbal metabolites of NDS and five vascular tone modulation G-protein-coupled receptors (GPCRs), including 5-HT1AR, 5-HT1BR, ß2-AR, AT1R, and ETBR, were assessed by molecular docking. Using network analysis and vasomotor experiment of the cerebral basilar artery, the potential material basis underlying the vascular regulatory effects of NDS was further explored. Results: The Naodesheng Effective Component Group (NECG) was found to induce relaxation of rat basilar artery rings precontracted using Endothelin-1 (ET-1) and KCl in vitro in a dose-dependent manner. Several metabolites of NDS, including C. tinctorius, C. pinnatifida, and P. notoginseng, were found to be the main plant resources of metabolites with high docking scores. Furthermore, several metabolites in NDS, including formononetin-7-glucoside, hydroxybenzoyl-coumaric anhydride, methoxymecambridine, puerarol, and pyrethrin II, were found to target multiple vascular GPCRs. Metabolites with moderate-to-high binding energy were verified to have good rat basilar artery-relaxing effects, and the maximum artery relaxation effects of all three metabolites, namely, isorhamnetin, kaempferol, and daidzein, were found to exceed 90%. Moreover, metabolites of NDS were found to exert a synergistic effect by interacting with vascular GPCR targets, and these metabolites may contribute to the cerebrovascular regulatory function of NDS. Discussion: The study reports that various metabolites of NDS contribute to its vascular tone regulating effects and demonstrates the multi-component and multi-target characteristics of NDS. Among them, metabolites with moderate-to-high binding scores in NDS may play an important role in regulating vascular function.

Fe Single-Atom Carbon Dots Nanozyme Collaborated with Nucleic Acid Exonuclease III-Driven DNA Walker Cascade Amplification Strategy for Circulating Tumor DNA Detection.

Circulating tumor DNA (ctDNA), as a next-generation tumor marker, enables early screening and monitoring of cancer through noninvasive testing. Exploring the development of new methods for ctDNA detection is an intriguing study. In this work, a unique electrochemical biosensor for the ctDNA detector was constructed in the first utilizing Fe single-atom nanozymes-carbon dots (SA Fe-CDs) as a signaling carrier in collaboration with a DNA walker cascade amplification strategy triggered by nucleic acid exonuclease III (Exo III). The electrochemical active surface area of AuNPs/rGO modified onto a glassy carbon electrode (AuNPs/rGO/GCE) was about 1.43 times that of a bare electrode (bare GCE), with good electrical conductivity alongside a high heterogeneous electron transfer rate (5.81 × 10-3 cm s-1), that is, as well as the ability to load more molecules. Sequentially, the DNA walker cascade amplification strategy driven by Exo III effectively converted the target ctDNA into an amplified biosignal, ensuring the sensitivity and specificity of ctDNA. Ultimately, the electrochemical signal was further amplified by introducing SA Fe-CDs nanozymes, which could serve as catalysts for 3,3',5,5'-tetramethylbenzidine (TMB) oxidation with facile responding (Vmax = 0.854 × 10-6 M s-1) and robust annexation (Km = 0.0069 mM). The integration of the triple signal amplification approach achieved detection limits as low as 1.26 aM (S/N = 3) for a linearity spanning from 5 aM to 50 nM. In this regard, our proposal for a biosensor with exceptional assay properties in complicated serum environments had great potential for early and timely diagnosis of cancer.

Pattern-based colorimetric sensor array chip for discrimination of Baijiu aromas.

Gas mixtures are comprised of numerous complex components, making the accurate identification a continuing challenge due to the significant limitations of existing detection methods. Herein, we developed a low-cost and sensitive pattern-based colorimetric sensor array chip for the identification of typical gas mixtures - Baijiu aroma. Specifically, three nanomaterials (AuNPs, MoS2 and ZIF-8) were prepared to adsorb gas molecules and enhance the reaction of trace gases with sensor arrays. The colorimetric sensor array chip took only 5 min to complete the recognition of Baijiu aromas and effectively avoided recognition errors caused by sommelier olfactory fatigue. Notably, the hierarchical cluster analysis (HCA) revealed no confusion or errors in the results of 80 tests across the five trials involving 16 commercial Baijius. Even fake Baijius with similar ingredients could be easily identified, demonstrating the excellent analytical capabilities of the system in Baijiu identification and its significant potential for quality control of Baijius.

Effects of polyethylene, polylactic acid, and tire particles on the sediment microbiome and metabolome at high and low temperatures.

Global warming has led to a high incidence of extreme heat events, and the frequent occurrence of extreme heat events has had extensive and far-reaching impacts on wetland ecosystems. The widespread distribution of plastics in the environment, including polyethylene (PE), polylactic acid (PLA), and tire particles (TPs), has caused various environmental problems. Here, high-throughput sequencing techniques and metabolomics were used for the first time to investigate the effects of three popular microplastic types: PE, PLA, and TP, on the sediment microbiome and the metabolome at both temperatures. The microplastics were incorporated into the sediment at a concentration of 3% by weight of the dry sediment (wt/wt), to reflect environmentally relevant conditions. Sediment enzymatic activity and physicochemical properties were co-regulated by both temperatures and microplastics producing significant differences compared to controls. PE and PLA particles inhibited bacterial diversity at low temperatures and promoted bacterial diversity at high temperatures, and TP particles promoted both at both temperatures. For bacterial richness, only PLA showed inhibition at low temperature; all other treatments showed promotion. PE, PLA, and TP microplastics changed the community structure of sediment bacteria, forming two clusters at low and high temperatures. Furthermore, PE, PLA, and TP changed the sediment metabolic profiles, producing differential metabolites such as lipids and molecules, organic heterocyclic compounds, and organic acids and their derivatives, especially TP had the most significant effect. These findings contribute to a more comprehensive understanding of the potential impact of microplastic contamination.IMPORTANCEIn this study, we added 3% (wt/wt) microplastic particles, including polyethylene, polylactic acid, and tire particles, to natural sediments under simulated laboratory conditions. Subsequently, we simulated the sediment microbial and ecosystem responses under different temperature conditions by incubating them for 60 days at 15°C and 35°C, respectively. After synthesizing these results, our study strongly suggests that the presence of microplastics in sediment ecosystems and exposure under different temperature conditions may have profound effects on soil microbial communities, enzyme activities, and metabolite profiles. This is important for understanding the potential hazards of microplastic contamination on terrestrial ecosystems and for developing relevant environmental management strategies.

Temperature-dependent effects of microplastics on sediment bacteriome and metabolome.

The increasing prevalence of microplastics in the environment has become a concern for various ecosystems, including wetland ecosystems. Here, we investigated the effects of three popular microplastic types: polyethylene, polylactic acid, and tire particles at 5 °C and 25 °C on the sediment microbiome and metabolome at the 3% (w/w) level. Results indicated that temperature greatly influenced catalase and neutral phosphatase activities, whereas the type of microplastic had a more significant impact on urease and dehydrogenase activities. The addition of microplastic, especially tire particles, increased microbial diversity and significantly altered the microbial community structure and metabolic profile, leading to the formation of different clusters of microbial communities depending on the temperature. Nonetheless, the effect of temperature on the metabolite composition was less significant. Functional prediction showed that the abundance of functional genes related to metabolism and biogeochemical cycling increased with increasing temperature, especially the tire particles treatment group affected the nitrogen cycling by inhibiting ureolysis and nitrogen fixation. These observations emphasize the need to consider microplastic type and ambient temperature to fully understand the ecological impact of microplastics on microbial ecosystems.

High-Throughput Small Molecule Drug Screening For Age-Related Sleep Disorders Using Drosophila melanogaster.

Sleep, an essential component of health and overall well-being, often presents challenges for older individuals who frequently experience sleep disorders characterized by shortened sleep duration and fragmented patterns. These sleep disruptions also correlate with an increased risk of various illnesses in the elderly, including diabetes, cardiovascular diseases, and psychological disorders. Unfortunately, existing drugs for sleep disorders are associated with significant side effects such as cognitive impairment and addiction. Consequently, the development of new, safer, and more effective sleep disorder medications is urgently needed. However, the high cost and lengthy experimental duration of current drug screening methods remain limiting factors. This protocol describes a cost-effective and high-throughput screening method that utilizes Drosophila melanogaster, a species with a highly conserved sleep regulation mechanism compared to mammals, making it an ideal model for studying sleep disorders in the elderly. By administering various small compounds to aged flies, we can assess their effects on sleep disorders. The sleep behaviors of these flies are recorded using an infrared monitoring device and analyzed with the open-source data package Sleep and Circadian Analysis MATLAB Program 2020 (SCAMP2020). This protocol offers a low-cost, reproducible, and efficient screening approach for sleep regulation. Fruit flies, due to their short life cycle, low husbandry cost, and ease of handling, serve as excellent subjects for this method. As an illustration, Reserpine, one of the tested drugs, demonstrated the ability to promote sleep duration in elderly flies, highlighting the effectiveness of this protocol.

A meta-analytic cognitive framework of nudge and sludge.

Public and private institutions have gained traction in developing interventions to alter people's behaviours in predictable ways without limiting the freedom of choice or significantly changing the incentive structure. A nudge is designed to facilitate actions by minimizing friction, while a sludge is an intervention that inhibits actions by increasing friction, but the underlying cognitive mechanisms behind these interventions remain largely unknown. Here, we develop a novel cognitive framework by organizing these interventions along six cognitive processes: attention, perception, memory, effort, intrinsic motivation and extrinsic motivation. In addition, we conduct a meta-analysis of field experiments (i.e. randomized controlled trials) that contained real behavioural measures (n = 184 papers, k = 184 observations, N = 2 245 373 participants) from 2008 to 2021 to examine the effect size of these interventions targeting each cognitive process. Our findings demonstrate that interventions changing effort are more effective than interventions changing intrinsic motivation, and nudge and sludge interventions had similar effect sizes. However, these results need to be interpreted with caution due to a potential publication bias. This new meta-analytic framework provides cognitive principles for organizing nudge and sludge with corresponding behavioural impacts. The insights gained from this framework help inform the design and development of future interventions based on cognitive insights.

NG-SEM: an effective non-Gaussian structural equation modeling framework for gene regulatory network inference from single-cell RNA-seq data.

Inference of gene regulatory network (GRN) from gene expression profiles has been a central problem in systems biology and bioinformatics in the past decades. The tremendous emergency of single-cell RNA sequencing (scRNA-seq) data brings new opportunities and challenges for GRN inference: the extensive dropouts and complicated noise structure may also degrade the performance of contemporary gene regulatory models. Thus, there is an urgent need to develop more accurate methods for gene regulatory network inference in single-cell data while considering the noise structure at the same time. In this paper, we extend the traditional structural equation modeling (SEM) framework by considering a flexible noise modeling strategy, namely we use the Gaussian mixtures to approximate the complex stochastic nature of a biological system, since the Gaussian mixture framework can be arguably served as a universal approximation for any continuous distributions. The proposed non-Gaussian SEM framework is called NG-SEM, which can be optimized by iteratively performing Expectation-Maximization algorithm and weighted least-squares method. Moreover, the Akaike Information Criteria is adopted to select the number of components of the Gaussian mixture. To probe the accuracy and stability of our proposed method, we design a comprehensive variate of control experiments to systematically investigate the performance of NG-SEM under various conditions, including simulations and real biological data sets. Results on synthetic data demonstrate that this strategy can improve the performance of traditional Gaussian SEM model and results on real biological data sets verify that NG-SEM outperforms other five state-of-the-art methods.

The change of Siglec-9 expression in peripheral blood NK cells of SFTS patients can affect the function of NK cells.

OBJECTIVES: To investigate the changes and mechanism of Siglec-9 on NK cells in peripheral blood of patients with severe fever with thrombocytopenia syndrome (SFTS). METHODS: First, we used single-cell RNA sequencing to analyze the frequency of NK cells in Peripheral Blood Mononuclear Cells (PBMCs) of SFTS patients and healthy controls (HCs), as well as the differences in the genes on NK cells. Secondly, we analyzed the expression of Siglec-9 and other receptors on NK cells by flow cytometry. Thirdly, we analyzed the correlation between Siglec-9 on NK cells and DBV viral load in plasma. RESULTS: Compared with HCs, the frequency of NK cells in peripheral blood of SFTS patients was significantly decreased, and the activating receptors on NK cells were reduced. The expression of Siglec-9 on NK cells and the frequency of Siglec-9+NK cells decreased significantly in SFTS patients. The expression of Siglec-9 on CD16+CD56dim NK cells was negatively correlated with DBV viral load. In addition, Siglec-9+NK cells expressed higher levels of activating receptors and exhibited stronger effector functions than Siglec-9-NK cells. CONCLUSIONS: The decreased expression of Siglec-9 on NK cells predicts NK cell dysfunction in SFTS patients, suggesting that Siglec-9 may be a potential marker for functional NK cell subsets in SFTS patients.

Nudging policymakers on gendered impacts of policy.

Despite the proliferation of nudge research in the last few decades, very little published work aims to nudge the behavior of policymakers. Here we explore the impact of a well-established nudge on policymakers in the Northwest Territories of Canada. In a pre-registered randomized controlled trial, we emailed an invitation to policymakers (N = 263) to attend an online briefing on gendered impacts of policy. In the treatment condition (N = 133), the invitation contained personal stories of two women whose lives were disproportionally impacted by public policies more than men. In the control condition (N = 130), the invitation did not contain such stories. After the briefing, we sent all participants in both conditions a link to a public pledge that they could sign. The pledge was to lead and advocate for equity-oriented policymaking. Contrary to our prediction, there was a small backfiring effect where policymakers in the treatment condition (3.0%) were less likely to attend the briefing than the control condition (7.7%). However, two policymakers (1.5%) in the treatment condition signed the public pledge compared to one (0.8%) in the control condition. The current findings reveal the limits of using personal stories as a nudge to influence policymakers. We discuss insights gained from this experiment and follow-up debriefings with policymakers on how to improve future behavioral interventions designed to nudge policymakers.