Integrative analysis of the immunological significances of guanylate binding protein family genes in microsatellite stability colorectal cancer.

Background: Microsatellite stability (MSS) colorectal cancer (CRC) has poor sensitivity to immunotherapy and its underlying mechanisms are still unclear. Guanylate binding proteins (GBPs) are a family of GTPase involving innate immune responses by providing defense against invading microbes and pathogens. However, the immunological significances of GBPs in MSS CRC remain unknown. Methods: We utilized bioinformatic tools to comprehensively analysis the expression pattern, clinical relevance, prognostic value, biological function, and immunoregulation effect of distinct GBP members in MSS CRC. Results: The expression of all seven GBPs in MSS samples are remarkably decreased compared to microsatellite instability-high (MSI-H) samples. Among them, GBP1/2/4/5 are obviously correlated with distant metastasis status. High expression of GBP1/4/5/6 was remarkably related to favorable overall survival (OS) and progression-free survival (PFS) in CRC patients with MSS tumor. Subsequent enrichment analysis revealed that Interferon-gamma (IFN-γ) and NOD-like receptor signaling are the most relevant functions. Besides, the expression patterns of GBPs are remarkably associated with several tumor infiltrated immune cells (e.g. regulatory T cells, CD4+ T cells, and macrophages) and diverse immunoregulatory molecules (e.g. immune checkpoint biomarkers (ICBs) and major histocompatibility complex (MHC) molecules). Moreover, high GBP1/2/4/5 expression predicted better immunotherapy responsiveness in immunotherapy cohorts. Conclusion: These findings might provide novel insights for the identification of therapeutic targets and potential prognostic biomarkers of GBP family in CRC with MSS samples.

Protective effect of ferulic acid-hyaluronic acid copolymer against UVB irradiation in a human HaCaT cell line.

Excessive UVB exposure increased the production of reactive oxygen species (ROS), leading to oxidative damage and epidermal inflammation. To enhance UVB protection effect, a strong phenolic antioxidant, ferulic acid (FA) was designed onto HA via a free radical mediated method. Our previous work has confirmed its structural characterization and in vitro antioxidant. The aim of this study was to evaluate its protective effects against UVB-induced damage in human HaCaT cells. We observed a significant reduction in cell viability to 57.43 % following UVB exposure at a dose of 80 mJ/cm2. However, pretreatment with FA-HA (250 to 2000 µg·mL-1) significantly attenuated cytotoxicity in a dose-dependent manner. Furthermore, FA-HA was found to suppress the intracellular generation of ROS and up-regulated the expression of the antioxidant enzyme superoxide dismutase (SOD). The elevated levels of pro-inflammatory cytokines, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) as well as the mRNA expression of matrix metalloproteinase-1/9 (MMP-1/9) induced by UVB irradiation, were also effectively reduced by FA-HA. Additionally, FA-HA treatment decreases the phosphorylation of mitogen-activated protein kinase (MAPK) and activator protein-1 (AP-1), ultimately preventing apoptosis. These findings suggest that FA-HA is a promising candidate for UVB protection in skincare formulations.

Upregulation of phosphodiesterase 7A leads to the downregulation of cAMP-PKA-CREB-BDNF signaling and neuroinflammation in the hippocampus and contributes to concurrent chronic pain and depression in two mouse models.

BACKGROUND: Phosphodiesterases (PDEs) are enzymes that catalyze the hydrolysis of cyclic adenosine monophosphate AMP (cAMP) and/or cyclic guanosine monophosphate (cGMP). PDE inhibitors can mitigate chronic pain and depression when these disorders occur individually; however, there is limited understanding of their role in concurrent chronic pain and depression. We aimed to evaluate the mechanisms of action of PDE using two mouse models of concurrent chronic pain and depression. METHODS: C57BL/6J mice were subjected to partial sciatic nerve ligation (PSNL) to induce chronic neuropathic pain or injected with complete Freund's adjuvant (CFA) to induce inflammatory pain, and both animals showed depression-like behavior. First, we determined the change in PDE expression in both animal models. Next, we determined the effect of PDE7 inhibitor BRL50481 or hippocampal PDE7A knockdown on PSNL- or CFA-induced chronic pain and depression-like behavior. We also investigated the role of cAMP-protein kinase A (PKA)-cAMP response element binding protein (CREB)-brain-derived neurotrophic factor (BDNF) signaling and neuroinflammation in the effect of PDE7A inhibition on PSNL- or CFA-induced chronic pain and depression-like behavior. RESULTS: This induction of chronic pain and depression in the two animal models upregulated hippocampal PDE7A. Oral administration of PDE7 inhibitor, BRL50481, or hippocampal PDE7A knockdown significantly reduced mechanical hypersensitivity and depression-like behavior. Hippocampal PDE7 inhibition reversed PSNL- or CFA-induced downregulation of cAMP and BDNF and the phosphorylation of PKA, CREB and p65. cAMP agonist forskolin, reversed these changes and caused milder behavioral symptoms of pain and depression. BRL50481 reversed neuroinflammation in the hippocampus in PSNL mice. CONCLUSIONS: Hippocampal PDE7A mediated concurrent chronic pain and depression in both mouse models by inhibiting cAMP-PKA-CREB-BDNF signaling Inhibiting PDE7A or activating cAMP-PKA-CREB-BDNF signaling are potential strategies to treat concurrent chronic pain and depression.

Carotenoids modulate antioxidant pathways in In vitro models of Parkinson's disease: A comprehensive scoping review.

Parkinson's disease (PD) is the second most common neurodegenerative disease, and it has affected the living quality of elderly people significantly. PD is characterised by the accumulation of α-Synuclein and progressive loss of dopaminergic neurons at the substantia nigra pars compacta. In the pathogenesis of Parkinson's disease, α-Synuclein, oxidative stress, and electron transport chain (ETC) are the three main factors that contribute to the production of reactive oxygen species (ROS). Currently, there is no commercial disease-modifying agent available for PD; the first-line treatment, Levodopa (l-DOPA), could only relieve the symptoms of PD, with many side effects. Carotenoids, which encompass red, orange, and yellow pigments found in nature and contribute to the colouration of plants, have been associated with various health benefits, including anti-cancer and neuroprotective effects due to their antioxidant properties. This scoping review delves into the impact and underlying mechanisms of carotenoids on cell-based models of neurodegenerative diseases.

Cyclically conjugated porphyrin trimers linked through benzo[4,5]imidazo[2,1-a]isoindole bridges.

Cyclically conjugated porphyrin trimers were prepared via a concise synthetic method. Zn-Trimer-1 displayed strong exciton coupling, suggesting the presence of effective electronic interactions. UV-Vis absorption and fluorescence spectra obtained through titration studies on the donor-acceptor adduct (Zn-Trimer-1-C60Im) indicate the occurrence of excited state photo-events.

Association Between Inability to Stand at ICU Discharge and Readmission: A Historical Cohort Study.

OBJECTIVES: The aim of this study was to determine if being unable to stand at ICU discharge was associated with an increased probability of ICU readmission. DESIGN: A multicenter retrospective cohort study was conducted using the Toronto Intensive Care Observational Registry (iCORE) project. SETTING: Nine tertiary academic ICUs in Toronto, Canada, affiliated with the University of Toronto. PATIENTS: All patients admitted to ICUs participating in iCORE from September 2014 to January 2020 were included. Patients had to be mechanically ventilated for more than 4 hours to be included in iCORE. Exclusion criteria were death during the initial ICU stay, transfer to another institution not included in iCORE at ICU discharge, and a short ICU stay defined as less than 2 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main exposure in this study was the inability of the patient to stand at ICU discharge, documented daily in the database within the ICU Mobility Scale. The primary outcome of this study was readmission to the ICU. After adjusting for potential confounders, being unable to stand at ICU discharge was associated with increased odds of readmission (odds ratio, 1.85; 95% CI, 1.31-2.62; p < 0.001). CONCLUSIONS: In patients with an ICU stay of 2 days or more, being unable to stand at ICU discharge is associated with increased odds of readmission to the ICU.

Health economic evaluation of an artificial intelligence (AI)-based rapid nutritional diagnostic system for hospitalised patients: A multicentre, randomised controlled trial.

BACKGROUND & AIMS: Malnutrition is prevalent among hospitalised patients, and increases the morbidity, mortality, and medical costs; yet nutritional assessments on admission are not routine. This study assessed the clinical and economic benefits of using an artificial intelligence (AI)-based rapid nutritional diagnostic system for routine nutritional screening of hospitalised patients. METHODS: A nationwide multicentre randomised controlled trial was conducted at 11 centres in 10 provinces. Hospitalised patients were randomised to either receive an assessment using an AI-based rapid nutritional diagnostic system as part of routine care (experimental group), or not (control group). The overall medical resource costs were calculated for each participant and a decision-tree was generated based on an intention-to-treat analysis to analyse the cost-effectiveness of various treatment modalities. Subgroup analyses were performed according to clinical characteristics and a probabilistic sensitivity analysis was performed to evaluate the influence of parameter variations on the incremental cost-effectiveness ratio (ICER). RESULTS: In total, 5763 patients participated in the study, 2830 in the experimental arm and 2933 in the control arm. The experimental arm had a significantly higher cure rate than the control arm (23.24% versus 20.18%; p = 0.005). The experimental arm incurred an incremental cost of 276.52 CNY, leading to an additional 3.06 cures, yielding an ICER of 90.37 CNY. Sensitivity analysis revealed that the decision-tree model was relatively stable. CONCLUSION: The integration of the AI-based rapid nutritional diagnostic system into routine inpatient care substantially enhanced the cure rate among hospitalised patients and was cost-effective. REGISTRATION: NCT04776070 (https://clinicaltrials.gov/study/NCT04776070).

Optimizing Subsequent CARdiovascular Medication Reintroduction in the Intensive Care Unit.

Importance: Hospital admission for a critical illness episode creates communication breakpoints and can lead to medication discrepancies during hospital stays. Due to the patient's underlying condition and the care setting, chronic medications such as cardiovascular medication are often held, discontinued, or changed to alternative administration routes. Unfortunately, data on the optimal timing of cardiovascular drug reinitiation among intensive care unit (ICU) survivors are lacking. Objective: The primary objective of this study was to describe the prevalence of chronic cardiovascular medication taken before hospital admission and discontinued at ICU discharge and hospital discharge for critically ill patients. A secondary objective was to assess factors associated with medication discontinuation. Design setting and participants: We conducted a multicentered retrospective cohort study at 2 tertiary academic hospitals in Canada. All adult patients taking cardiovascular medication before ICU admission and surviving to hospital discharge between April 1, 2016, and April 1, 2017, were eligible. Main outcomes and measures: The main outcome of the study was the discontinuation of cardiovascular medication prescribed before ICU admission. The outcome was assessed through participants' chart review. Results: We included 352 patients with a median age of 71.0 years. A total of 155 patients (44.03%) had at least 1 cardiovascular medication discontinued during their stay. Our adjusted model uncovered 3 factors associated with cardiovascular medication discontinuation: male sex (odds ratio [OR] = 0.564, 95% confidence interval [CI] = 0.346-0.919), number of cardiovascular medications taken preadmission (OR = 1.669, 95% CI = 1.003-2.777 for 2 medications and OR = 3.170, 95% CI = 1.325-7.583), and the use of vasopressors (OR = 1.770, 95% CI = 1.045-2.997). Conclusion: Our study uncovered that cardiovascular medication discontinuation for ICU patients is frequent, especially for renin-angiotensin system (RAS) blockers. Data from our study could be used to reinforce site-specific protocols of medication reconciliation and optimization, as well as inform future protocols aimed at RAS blocker reinitiation follow-up.

Importance de cette étude: L'admission à l'hôpital pour un épisode de maladie grave crée des ruptures de communication et peut entraîner des écarts dans la médication pendant le séjour à l'hôpital. Il arrive souvent, selon l'état sous-jacent du patient et l'environnement de soins, que les médicaments destinés à traiter des maladies chroniques, comme les médicaments cardiovasculaires, soient poursuivis, cessés ou administrés par d'autres voies. On manque malheureusement de données sur le moment optimal pour la reprise du traitement cardiovasculaire chez les survivants des unités de soins intensifs (USI). Objectifs: L'objectif principal était de décrire la prévalence de l'arrêt, à la sortie de l'USI et de l'hôpital, des médicaments pris par les patients gravement malades pour traiter les maladies cardiovasculaires chroniques avant leur admission. Un objectif secondaire était d'évaluer les facteurs associés à l'arrêt du traitement. Conception sujets et cadre de l'étude: Nous avons mené une étude de cohorte rétrospective multicentrique dans deux hôpitaux universitaires tertiaires canadiens. Étaient admissibles tous les patients adultes qui prenaient des médicaments cardiovasculaires avant leur admission à l'USI entre le 1er avril 2016 et le 1er avril 2017 et qui avaient survécu jusqu'à leur sortie de l'hôpital. Mesures et principaux critères d'intérêt: Le principal critère d'intérêt était l'arrêt du traitement cardiovasculaire prescrit avant l'admission à l'USI. Ce critère a été établi par l'examen des dossiers des sujets. Résultats: Nous avons inclus 352 patients (âge médian : 71,0 ans) desquels 155 (44 %) avaient vu au moins un de leurs médicaments pour traiter une maladie cardiovasculaire cessé pendant leur séjour. Notre modèle corrigé a révélé trois facteurs associés à l'arrêt du traitement cardiovasculaire : être de sexe masculin (rapport de cotes [RC] : 0,564; IC95 % : 0,346-0,919), le nombre de médicaments cardiovasculaires pris avant l'admission (RC : 1,669; IC95 % : 1,003-2,777 pour deux médicaments, et RC : 3,170; IC95 % : 1,325-7,583) et l'utilisation de vasopresseurs (RC : 1,770; IC95 % : 1,045-2,997). Conclusion: Notre étude a révélé que l'arrêt du traitement contre les maladies cardiovasculaires chroniques, en particulier les inhibiteurs du SRA, est fréquent chez les patients hospitalisés aux soins intensifs. Les données de notre étude pourraient servir à renforcer les protocoles de bilan de médication et d'optimisation propre à chaque site de même que pour éclairer les futurs protocoles visant à assurer le suivi de la réinitiation des inhibiteurs du SRA.

Effect of black soldier fly larvae frass addition on humus content during low temperature co-composting.

Initiating aerobic fermentation under low temperature is the main challenge for winter livestock manure composting. This study aims to address this issue by applying black soldier fly larvae (BSFL) frass as a co-composting additive to enhance the low-temperature composting process. Specifically, this work explored the effects of chicken manure and BSFL frass co-composting on the temperature, humus content, and microorganisms with fresh weight ratio of 2:1, 1:1, 1:2 (w/w) at 6 °C. The result showed frass could rapidly rise the temperature to 50 °C and significantly increased the humus content by 15.6 % ∼ 26.3 %. Moreover, microbial analysis revealed that Sphingobacteriaceae accelerated temperature rise via low-temperature reproduction, creating proper temperature for thermophilic bacteria (Truepera and Georgia). Additionally, Cellulomonas and other bacteria promoted organic matter degradation and participated in humus formation. This study presents a novel solution for low-temperature composting, providing practical insights for improving manure management in winter.

Circulating extracellular vesicle-derived miR-1299 disrupts hepatic glucose homeostasis by targeting the STAT3/FAM3A axis in gestational diabetes mellitus.

BACKGROUND: Extracellular vesicles (EVs) are membrane-enclosed structures containing lipids, proteins, and RNAs that play a crucial role in cell-to-cell communication. However, the precise mechanism through which circulating EVs disrupt hepatic glucose homeostasis in gestational diabetes mellitus (GDM) remains unclear. RESULTS: Circulating EVs isolated from human plasma were co-cultured with mammalian liver cells to investigate the potential induction of hepatic insulin resistance by GDM-EVs using glucose output assays, Seahorse assays, metabolomics, fluxomics, qRT-PCR, bioinformatics analyses, and luciferase assays. Our findings demonstrated that hepatocytes exposed to GDM-EVs exhibited increased gluconeogenesis, attenuated energy metabolism, and upregulated oxidative stress. Particularly noteworthy was the discovery of miR-1299 as the predominant miRNA in GDM-EVs, which directly targeting the 3'-untranslated regions (UTR) of STAT3. Our experiments involving loss- and gain-of-function revealed that miR-1299 inhibits the insulin signaling pathway by regulating the STAT3/FAM3A axis, resulting in increased insulin resistance through the modulation of mitochondrial function and oxidative stress in hepatocytes. Moreover, experiments conducted in vivo on mice inoculated with GDM-EVs confirmed the development of glucose intolerance, insulin resistance, and downregulation of STAT3 and FAM3A. CONCLUSIONS: These results provide insights into the role of miR-1299 derived from circulating GDM-EVs in the progression of insulin resistance in hepatic cells via the STAT3/FAM3A axis and downstream metabolic reprogramming.

Metabolomic analysis of Agkistrodon haly venom poisoning mouse treatment by Jidesheng snake pill based on GC-MS.

Introduction: Snakebites are acute systemic toxic diseases caused by snake venom entering the body through wounds. Failure to use antivenom immediately and difficulty in obtaining antivenoms are frequently responsible for worsening disease. Traditional Chinese medicine is commonly used to supplement and replace antivenom in treating snakebites. The Jidesheng snake pill (JDS) is a widely used traditional Chinese medicine that has achieved good clinical therapeutic effects; however, its mechanism remains unclear. Therefore, metabolomics techniques were employed to explore the pathophysiological mechanisms of JDS treatment of Agkistrodon halys (Ah) snake venom-poisoned mice. Methods: The Ah group mouse model was established by intramuscular injection of Ah venom into the hind legs of the mice. The Ah venom + JDS group model was established using JDS after the affected area was treated with Ah venom. Hematoxylin and eosin (HE) staining was used to evaluate the severity of gastrocnemius injury. Quantitative polymerase chain reaction (qPCR) was utilized to detect the mRNA expression of vascular cell adhesion molecule-1 (VCAM-1), muscle-specific creatine kinase (CKM), thrombin antithrombin complex (TAT), and tumor necrosis factor-alpha (TNF-α). Gas chromatography-mass spectrometry (GC-MS) was performed with multivariate statistical analysis to provide new insights into the global metabolic profile of Ah venom-poisoned mice. Results: HE staining revealed increased red cell necrosis, local hemorrhage, and neutrophil infiltration in the Ah venom group than in the control group. Several compounds were identified, including lipids, amino acids, peptides, and organooxygen. Eighty differential metabolites were screened between the control group and the Ah venom group, and 24 were screened between the Ah venom and JDS groups. The mechanism of Ah venom poisoning in mice may involve aminoacyl-tRNA biosynthesis, various amino acid metabolism disorders, tricarboxylic acid circulation disorders, and abnormal fatty acid metabolism. JDS may reduce symptoms by affecting long-chain fatty acid and amino acid metabolism and promoting nicotinamide-nicotinamide metabolism. Conclusion: Our results suggest that metabolomics has huge prospects for elucidating the pathophysiology of Agkistrodon haly venom poisoning and therapeutic mechanisms of JDS.

Regulating Aggregation-Induced Emission Luminogen for Multimodal Imaging-Navigated Synergistic Therapy Involving Anti-Angiogenesis.

As a new avenue for cancer research, phototheranostics has shown inexhaustible and vigorous vitality as it permits real-time diagnosis and concurrent in situ therapy upon non-invasive light-initiation. However, construction of an advanced material, allowing prominent phototheranostic outputs and synchronously surmounting the inherent deficiency of phototheranostics, would be an appealing yet significantly challenging task. Herein, an aggregation-induced emission (AIE)-active luminogen (namely DBD-TM) featured by intensive electron donor-acceptor strength and twisted architecture with finely modulated intramolecular motion, is tactfully designed and prepared. DBD-TM simultaneously possessed fluorescence emission in the second near-infrared (NIR-II) region and high-efficiency photothermal conversion. By integrating DBD-TM with anti-angiogenic agent sorafenib, a versatile nanomaterial is smoothly fabricated and utilized for trimodal imaging-navigated synergistic therapy involving photothermal therapy and anti-angiogenesis toward cancer. This advanced approach is capable of affording accurate tumor diagnosis, complete tumor elimination, and largely restrained tumor recurrence, evidently denoting a prominent theranostic formula beyond phototheranostics. This study will offer a blueprint for exploiting a new generation of cancer theranostics.

Identification of SDG gene family members and exploration of flowering related genes in different cultivars of chrysanthemums and their wild ancestors.

The SET domain genes (SDGs) are significant contributors to various aspects of plant growth and development, mainly includes flowering, pollen development, root growth, regulation of the biological clock and branching patterns. To clarify the biological functions of the chrysanthemum SDG family, the SDG family members of four chrysanthemum cultivars and three related wild species were identified; their physical and chemical properties, protein domains and conserved motifs were predicted and analyzed. The results showed that 59, 67, 67, 102, 106, 114, and 123 SDGs were identified from Chrysanthemum nankingense, Chrysanthemum lavandulifolium, Chrysanthemum seticuspe, Chrysanthemum × morifolium cv. 'Hechengxinghuo', 'Zhongshanzigui', 'Quanxiangshuichang' and 'Jinbeidahong', respectively. The SDGs were divided into 5-7 subfamilies by cluster analysis; different conserved motifs were observed in particular families. The SDGs of C. lavandulifolium and C. seticuspe were distributed unevenly on 9 chromosomes. SDG promoters of different species include growth and development, photo-response, stress response and hormone responsive elements, among them, the cis-acting elements related to MeJA response had the largest proportion. The expression of chrysanthemum SDG genes was observed for most variable selected genes which has close association with important Arabidopsis thaliana genes related to flowering regulation. The qPCR results showed that the expression trend of SDG genes varied in different tissues at different growth stages with high expression in the flowering period. The ClSDG29 showed higher expression in the flower and bud tissues, which indicate that ClSDG29 might be associated with flowering regulation in chrysanthemum. In summary, the results of this study can provide a basis for subsequent research on chrysanthemum flowering time regulation.

Phosphodiesterase 7 inhibitor reduces stress-induced behavioral and cytoarchitectural changes in C57BL/6J mice by activating the BDNF/TrkB pathway.

Background: Phosphodiesterase 7 (PDE7) plays a role in neurological function. Increased expression and activity of PDE7 has been detected in several central nervous system diseases. However, the role of PDE7 in regulating stress levels remains unclear. Thus, this study aimed to determine whether and how PDE7 involved in the stress-induced behavioral and neuron morphological changes. Methods: The single prolonged stress (SPS) was used to build a stress exposure model in C57BL/6 J mice and detected PDE7 activity in hippocampus, amygdala, prefrontal cortex and striatum. Next, three doses (0.2, 1, and 5 mg/kg) of the PDE7 inhibitor BRL-50481 were intraperitoneally administered for 10 days, then behavioral, biochemical, and morphological tests were conducted. Results: PDE7 activity in hippocampus of mice significantly increased at all times after SPS. BRL-50481 significantly attenuated SPS induced anxiety-like behavior and fear response in both context and cue. In addition, BRL-50481 increased the levels of key molecules in the cAMP signaling pathway which were impaired by SPS. Immunofluorescent staining and Sholl analysis demonstrated that BRL-50481 also restored the nucleus/cytoplasm ratio of hippocampal neurons and improved neuronal plasticity. These effects of BRL-50481 were partially blocked by the TrkB inhibitor ANA-12. Conclusion: PDE7 inhibitors attenuate stress-induced behavioral changes by protecting the neuron cytoarchitecture and the neuronal plasticity in hippocampus, which is mediated at least partly through the activation of BDNF/TrkB signaling pathway. These results proved that PDE7 is a potential target for treating stress-induced behavioral and physiological abnormalities.

NMC3D: Non-Overlapping Multi-Camera Calibration Based on Sparse 3D Map.

With the advancement of computer vision and sensor technologies, many multi-camera systems are being developed for the control, planning, and other functionalities of unmanned systems or robots. The calibration of multi-camera systems determines the accuracy of their operation. However, calibration of multi-camera systems without overlapping parts is inaccurate. Furthermore, the potential of feature matching points and their spatial extent in calculating the extrinsic parameters of multi-camera systems has not yet been fully realized. To this end, we propose a multi-camera calibration algorithm to solve the problem of the high-precision calibration of multi-camera systems without overlapping parts. The calibration of multi-camera systems is simplified to the problem of solving the transformation relationship of extrinsic parameters using a map constructed by multiple cameras. Firstly, the calibration environment map is constructed by running the SLAM algorithm separately for each camera in the multi-camera system in closed-loop motion. Secondly, uniformly distributed matching points are selected among the similar feature points between the maps. Then, these matching points are used to solve the transformation relationship between the multi-camera external parameters. Finally, the reprojection error is minimized to optimize the extrinsic parameter transformation relationship. We conduct comprehensive experiments in multiple scenarios and provide results of the extrinsic parameters for multiple cameras. The results demonstrate that the proposed method accurately calibrates the extrinsic parameters for multiple cameras, even under conditions where the main camera and auxiliary cameras rotate 180°.

Identification of Phosphodiesterase-7A (PDE7A) as a Novel Target for Reducing Ethanol Consumption in Mice.

BACKGROUND: Ethanol elicits a rapid stimulatory effect and a subsequent, prolonged sedative response, which are potential predictors of EtOH consumption by decreasing adenosine signaling; this phenomenon also reflects the obvious sex difference. cAMP (cyclic Adenosine Monophosphate)-PKA (Protein Kinase A) signaling pathway modulation can influence the stimulatory and sedative effects induced by EtOH in mice. This study's objective is to clarify the role of phosphodiesterase (PDE) in mediating the observed sex differences in EtOH responsiveness between male and female animals. METHODS: EtOH was administered i.p. for 7 days to identify the changes in PDE isoforms in response to EtOH treatment. Additionally, EtOH consumption and preference of male and female C57BL/6J mice were assessed using the drinking-in-the-dark and 2-bottle choice tests. Further, pharmacological inhibition of PDE7A heterozygote knockout mice was performed to investigate its effects on EtOH-induced stimulation and sedation in both male and female mice. Finally, Western blotting analysis was performed to evaluate the alterations in cAMP-PKA/Epac2 pathways. RESULTS: EtOH administration resulted in an immediate upregulation in PDE7A expression in female mice, indicating a strong association between PDE7A and EtOH stimulation. Through the pharmacological inhibition of PDE7A KD mice, we have demonstrated for the first time, to our knowledge, that PDE7A selectively attenuates EtOH responsiveness and consumption exclusively in female mice, whichmay be associated with the cAMP-PKA/Epac2 pathway and downstream phosphorylation of CREB and ERK1/2. CONCLUSIONS: Inhibition or knockdown of PDE7A attenuates EtOH responsivenessand consumption exclusively in female mice, which is associated with alterations in the cAMP-PKA/Epac2 signaling pathways, thereby highlighting its potential as a novel therapeutic target for alcohol use disorder.

The attenuation of gut microbiota-derived short-chain fatty acids elevates lipid transportation through suppression of the intestinal HDAC3-H3K27ac-PPAR-γ axis in gestational diabetes mellitus.

Gut flora is considered to modulate lipid transport from the intestine into the bloodstream, and thus may potentially participate in the development of GDM. Although previous studies have shown that the intestinal microbiota influences lipid transport and metabolism in GDM, the precise mechanisms remain elusive. To address this, we used a high-fat diet (HFD)-induced GDM mouse model and conducted 16s rRNA sequencing and fecal metabolomics to assess gut microbial community shifts and associated metabolite changes. Western blot, ELISA, and chromatin immunoprecipitation (ChIP) were utilized to elucidate how gut microbiota affect intestinal lipid transport and the insulin sensitivity of hepatic, adipose, and skeletal muscle tissues. We found that HFD impaired the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) in pregnant mice. 16s rRNA sequencing demonstrated profound compositional changes, especially in the relative abundances of Firmicutes and Bacteroidetes. Metabolomics analysis presented a decline in the concentration of short-chain fatty acids (SCFAs) in the GDM group. Western blot analyses showed an upregulation of HDAC3 and a concurrent reduction in H3K27 acetylation in the intestine. ChIP-qPCR showed that PPAR-γ was inhibited, which in turn activated lipid-transporter CD36. ELISA and insulin signaling pathway detection in insulin-target organs showed high concentrations of circulating fatty acids and triglycerides and insulin resistance in insulin-target organs. Our results suggest that gut microbiota is closely associated with the development of GDM, partly because decreased gut flora-associated SCFAs activate CD36 by suppressing the HDAC3-H3K27ac-PPAR-γ axis to transport excessive fatty acids and triglycerides into blood circulation, thereby dysregulating the insulin sensitivity of insulin target organs.

A preliminary study to identify critical factors for evaluating the effect of car-lock sounds on drivers.

Car-lock sounds are designed to inform the lock status of vehicles. However, drivers often experience a lack of confidence regarding whether the car is locked, and car thefts persistently occur, frequently attributed to unlocked doors. Without identification of critical factors for evaluating effects of car-lock sounds on drivers, a strategy to car-lock sound design with increased locking efficiency remains implicit. This study proposes a method to identify critical factors influencing drivers' perceived certainty of car-lock status and behaviours during car-locking. An experiment was conducted to simulate the locking process and verbal protocol analysis was employed to comprehend participants' cognitive processes and behaviours. The results show that mechanical sound yielded high certainty and few hesitations, while tonal and crisp sound elicited low certainty and frequent hesitations. Seven critical factors on participants' behaviours and cognitive processes were identified, which provides a data-driven approach for future research in car-lock sounds evaluation and design.

The effect of car-lock sounds on drivers is significant to inform the locking status of vehicles. However, the strategy for car-lock sounds evaluation remains implicit. This study proposes a method to identify critical factors on drivers' behaviours and cognitive processes that would inform further car-lock sounds evaluation and design.

Enhancing user experience in the digital service environment: A comprehensive study on the design and evaluation of internet-based healthcare products.

RATIONALE: In the era of burgeoning digital technology, healthcare is a challenging transformative change towards virtual and digital platforms. Internet-based healthcare services are emerging as a popular trend within the medical area. User experience (UX) is paramount for the healthcare service, as it significantly influences experience satisfaction and fosters user viscosity. Gaining a profound understanding of users' demands and crafting services that align with their expectations is essential. METHODS: Consequently, exploring an effective design approach for the digital healthcare service that prioritizes UX along with utilizing a comprehensive evaluation methodology to handle UX data, is of profound importance. This study introduces a design methodology for Internet-based healthcare products grounded in the UX and mental (UX-M) model. Aiming to refine the Internet-based healthcare product design by integrating insights from the experience data, it employs the Delphi-ANP and the fuzzy comprehensive evaluation to determine evaluation indexes and conduct experiential assessments. RESULTS: The UX evaluation results of existing schemes are compared with the proposed design scheme of the intelligent guidance and internet hospital. The findings indicate that the UX evaluation of Internet-based medical services with the proposed method outperforms the existing schemes. CONCLUSIONS: On the one hand, UX research of Internet-based healthcare products can significantly enhance service satisfaction for patients utilizing online medical treatments. On the other hand, the analysis of experience-based evaluation empowers designers to refine and improve UX design of Internet-based medical services. Such research endeavors are critical for enhancing the overall quality of service offerings and elevating user satisfaction in the digital healthcare landscape.