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Introduction: Low skeletal muscle mass and high adipose tissue coexist across the body weight spectrum and independently predict the survival ratio of colorectal cancer (CRC) patients. This combination may lead to a mutually exacerbating vicious cycle. Tumor-associated metabolic conditions primarily affect subcutaneous adipose tissue, but the nature and direction of its relationship with skeletal muscle are unclear. This study aims to examine the bidirectional causal relationship between skeletal muscle index (SMI) and subcutaneous fat index (SFI) during the perioperative period in CRC patients; as well as to validate the association between perioperative SMI, SFI, and CRC prognosis. Methods: This population-based retrospective cohort study included patients with stage I-III colorectal cancer who underwent radical resection at the Third Affiliated Hospital of Kunming Medical University between September 2012 and February 2019. Based on inclusion and exclusion criteria, 1,448 patients were analyzed. Preoperative (P1), 2 months postoperative (P2), and 5 months postoperative (P3) CT scans were collected to evaluate the skeletal muscle index (SMI; muscle area at the third lumbar vertebra divided by height squared) and subcutaneous fat index (SFI; subcutaneous fat area at the third lumbar vertebra divided by height squared). A random intercept cross-lagged panel model (RI-CLPM) was used to examine the intra-individual relationship between SMI and SFI, and Cox regression was employed to assess the association between SMI, SFI, recurrence-free survival (RFS), and overall survival (OS). Results: The median age at diagnosis was 59.00 years (IQR: 51.00-66.00), and 587 patients (40.54%) were female. RI-CLPM analysis revealed a negative correlation between SFI and subsequent SMI at the individual level: P1-P2 (ß = -0.372, p = 0.038) and P2-P3 (ß = -0.363, p = 0.001). SMI and SFI showed a negative correlation during P1-P2 (ß = -0.363, p = 0.001) but a positive correlation during P2-P3 (ß = 0.357, p = 0.006). No significant correlation was found between the random intercepts of SFI and SMI at the between-person level (r = 0.157, p = 0.603). The Cox proportional hazards multivariate regression model identified that patients with elevated SFI had poorer recurrence-free survival (HR, 1.24; 95% CI: 1.00-1.55). Compared to patients with normal preoperative SMI and SFI, those with low SMI or high SFI had poorer recurrence-free survival (HR, 1.26; 95% CI: 1.03-1.55) and overall survival (HR, 1.39; 95% CI: 1.04-1.87). However, no significant association between SMI and SFI and the prognosis of colorectal cancer patients was observed postoperatively. Conclusion: In CRC patients, preoperative muscle loss leads to postoperative fat accumulation, exacerbating muscle loss in a feedback loop. Elevated preoperative SFI predicts poorer survival outcomes. Monitoring SMI and SFI is crucial as prognostic indicators, despite non-significant postoperative associations. Further research is needed to improve patient outcomes.

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PURPOSE: Traditional fasting causes considerable discomfort without added assurance of security, whereas oral carbohydrate beverage offers an alternative to improve medical experience. This study aims to explore the impact of different types and dosages of oral fluids loading before painless bidirectional endoscopy on the gastric emptying and wellbeing. METHODS: 180 patients arranged for bidirectional endoscopy with intravenous anesthesia were randomized: patients in the control group (Group C) obeyed standard fasting; the 200 mL carbohydrate group (Group P1), 400 mL carbohydrate group (Group P2), 200 mL water group (Group W1) and 400 mL water group (Group W2) respectively consumed 200 mL or 400 mL corresponding clear liquids 2 h before the procedure. Gastric emptying metrics under ultrasound, subjective comfort indexes, periprocedural blood glucose and vital signs were contrasted among the groups. RESULTS: No significant differences were detected in the gastric emptying including CSA (cross-sectional area), GV (gastric volume), cGV (corrected gastric volume) and the three-point grading system among groups, and none had a cGV > 1.5 mL/kg before anesthesia. Participants in Group P2 experienced less preprocedural thirst and mouth dryness, so as the postprocedural thirst, mouth dryness and hunger. Periprocedural blood glucose and MAP had the similar trend in all groups. The occurrence of hypotension, bradycardia, hypoxia, and the required norepinephrine was comparable among the groups. CONCLUSIONS: Oral beverage loading with 200 mL or 400 mL can be safely applicated 2 h before painless bidirectional endoscopy without increasing the gastric volume. 400 mL carbohydrate solution effectively relieves the discomfort and could serve as a consideration. TRIAL REGISTRATION: Registered in the Chinese Clinical Trial Registry on December 5, 2023 (ChiCTR2300078319).

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BACKGROUND: Lipid droplet (LD) is a metabolically active organelle, which changes dynamically with the metabolic state and energy requirements of cells. Proteins that either insert into the LD phospholipid monolayer or are present in the cytoplasm, playing a crucial role in lipid homeostasis and signaling regulation, are known as LD-associated proteins. METHODS: The keywords "lipid droplets" and "metabolic diseases" were used to obtain literature on LD metabolism and pathological mechanism. After searching databases including Scopus, OVID, Web of Science, and PubMed from 2013 to 2024 using terms like "lipid droplets", "lipid droplet-associated proteins", "fatty liver disease", "diabetes", "diabetic kidney disease", "obesity", "atherosclerosis", "hyperlipidemia", "natural drug monomers" and "natural compounds", the most common natural compounds were identified in about 954 articles. Eventually, a total of 91 studies of 10 natural compounds reporting in vitro or in vivo studies were refined and summarized. RESULTS: The most frequently used natural compounds include Berberine, Mangostin, Capsaicin, Caffeine, Genistein, Epigallocatechin-3-gallate, Chlorogenic acid, Betaine, Ginsenoside, Resveratrol. These natural compounds interact with LD-associated proteins and help ameliorate abnormal LDs in various metabolic diseases. CONCLUSION: Natural compounds involved in the regulation of LDs and LD-associated proteins hold promise for treating metabolic diseases. Further research into these interactions may lead to new therapeutic applications.

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BACKGROUND: Cognitive impairment (CI) is now well-accepted as a complication and comorbidity of diabetes mellitus (DM), becoming a serious medical and social problem. Jiao-tai-wan (JTW), one of noted traditional Chinese medicine (TCM), showed dual therapeutic effects on DM and CI. Nevertheless, the potential mechanism is unclear. PURPOSE: This study sought to investigate the mechanism how JTW protected against DM and CI and screen the active component in JTW. METHODS: Db/db mice were used as mouse models. Mice were treated by gavage with 0.9 % saline (0.1 mL/10g/d), low dose of JTW (2.4 g/kg/d) or high dose of JTW (4.8 g/kg/d) for 8 weeks separately. To access the effects of JTW, the levels of OGTT, HOMA-IR, blood lipids, inflammatory cytokines in serum and hippocampus were measured, behavioral tests were conducted, and histopathological changes were observed. The mechanism exploration was performed via network pharmacology, RT-qPCR, western blot, and immunofluorescence staining (IF). The impact and mechanism of coptisine in vitro were investigated using BV2 cells induced by LPS as cellular models. In vitro experiments were conducted in two parts. The first part comprised four groups: Control group, LPS group, LPS+LCOP group and LPS+HCOP group. The second part consisted of four groups: Control group, LPS group, LPS+HCOP group, and LPS+ Fed group. The western blot and RT-qPCR methods were used to examine the changes in biomarkers of the JAK2/STAT3 signaling pathways in BV2 cells. RESULTS: The results demonstrated that JTW could improve OGTT and HOMA-IR, reduce the serum levels of LDL-C, HDL-C, TG, and TC, restore neuronal dysfunction and synaptic plasticity, and decrease the deposition of Aß in the hippocampus. The findings from ELISA, IF, and RT-qPCR revealed that JTW could alleviate microglial activation and inflammatory status in vivo and coptisine could play the same role in vitro. Moreover, the changes of the JAK2/STAT3 signaling pathway in LPS-induced BV2 cells or hippocampus of db/db mice were distinctly reversed by coptisine or JTW, respectively. CONCLUSION: Our study suggested that JTW and its effective component coptisine could alleviate diabetes mellitus-related cognitive impairment, closely linked to the JAK2/STAT3 signaling pathway.

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This study proposed the evolution of self-assembled amphiphilic colloidal particles in Strong-Flavor (SF) Baijiu based on Ostwald ripening for the first time. The evolution process occurs in two stages: disordered amphiphilic molecules self-assemble into small colloidal particles and subsequently undergo Oswald ripening to form larger hydrophobic particles. Microscopic observations revealed the average size of oil-like spherical colloidal particles in Baijiu increased from 1.86 µm to 2.96 µm while the number of particles decreased by 39.50% during the 16-year cellaring process of SF Baijiu, consistent with the particle size trend observed via laser scattering. During fusion process, the charge-to-mass ratio of positively charged colloidal particles decreased, leading ζ-potential decreased from 23.7 mV to 4.66 mV within 16 years of storage. The electrochemical impedance spectroscopy approach tracked the unidirectional variation in the dielectric constant during evolution of SF Baijiu, reflecting the gradual expansion of colloidal particles, which aligns with the evolution trend observed in molecular dynamics simulations. By integrating direct microscopic observations of amphiphilic colloidal particles with electrochemical techniques, the evolution of Baijiu samples is capable to be evaluated in-situ, laying the foundation for intelligent Baijiu aging monitoring technology.

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Terbuthylazine (TBA) is a common triazine herbicide used in agricultural production, which causes toxic damage in multiple tissues. Hesperidin (HSP) is a flavonoid derivative that has anti-inflammatory, antioxidant and cytoprotective effects, but its role in reducing toxic damage caused by pesticides is still unclear. In this study, we aimed to investigate the toxic effect of TBA exposure on chicken hepatocytes and the therapeutic effect of HSP on the TBA-induced hepatotoxicity. Our results demonstrated that HSP could alleviate TBA exposure-induced endoplasmic reticulum (ER) stress. Interestingly, TBA significantly disrupted the integrity of mitochondria-associated endoplasmic reticulum membrane (MAM), while HSP treatment showed the opposite tendency. In addition, TBA could significantly trigger ferroptosis in liver, and HSP treatment reversed ferroptosis under TBA exposure. These results suggested that HSP could inhibit ER stress and alleviate ferroptosis under TBA exposure via maintaining MAM integrity, which provided a novel strategy to take precautions against TBA toxicity.

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OBJECTIVE: Most cases of hepatocellular carcinoma (HCC) arise as a consequence of cirrhosis. In this study, our objective is to construct a comprehensive diagnostic model that investigates the diagnostic markers distinguishing between cirrhosis and HCC. METHODS: Based on multiple GEO datasets containing cirrhosis and HCC samples, we used lasso regression, random forest (RF)-recursive feature elimination (RFE) and receiver operator characteristic analysis to screen for characteristic genes. Subsequently, we integrated these genes into a multivariable logistic regression model and validated the linear prediction scores in both training and validation cohorts. The ssGSEA algorithm was used to estimate the fraction of infiltrating immune cells in the samples. Finally, molecular typing for patients with cirrhosis was performed using the CCP algorithm. RESULTS: The study identified 137 differentially expressed genes (DEGs) and selected five significant genes (CXCL14, CAP2, FCN2, CCBE1 and UBE2C) to construct a diagnostic model. In both the training and validation cohorts, the model exhibited an area under the curve (AUC) greater than 0.9 and a kappa value of approximately 0.9. Additionally, the calibration curve demonstrated excellent concordance between observed and predicted incidence rates. Comparatively, HCC displayed overall downregulation of infiltrating immune cells compared to cirrhosis. Notably, CCBE1 showed strong correlations with the tumour immune microenvironment as well as genes associated with cell death and cellular ageing processes. Furthermore, cirrhosis subtypes with high linear predictive scores were enriched in multiple cancer-related pathways. CONCLUSION: In conclusion, we successfully identified diagnostic markers distinguishing between cirrhosis and hepatocellular carcinoma and developed a novel diagnostic model for discriminating the two conditions. CCBE1 might exert a pivotal role in regulating the tumour microenvironment, cell death and senescence.

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A technique for monitoring chemical oxygen demand (COD), total nitrogen (TN), ammonia (N-NH4), and phosphate (P-PO4) in surface water with a targeted signal multielectrode system (Cu, Ir, Rh, Co(OH)2, and Zr(OH)4 electrodes) is proposed for the first time. Each water quality index is specifically detected by at least two electrodes with distinct selectivity sensing mechanisms. Cyclic voltammetry and electrochemical impedance measurements are employed for multidimensional signal acquisition, complemented by normalization and Least Absolute Shrinkage and Selection Operator (LASSO) for principal feature extraction and dimension reduction. Multiple linear regression (MLR), partial least-squares (PLS), and eXtreme Gradient Boosting (XGBoost) were employed to evaluate the established prediction model. The precisions of the multielectrode system are ±10%/±5 ppm of COD, ±10%/±0.2 ppm of TN, ±5%/±0.1 ppm of N-NH4, and ±5%/±0.01 ppm of P-PO4. The analysis time of the multielectrode system is reduced from hours to minutes compared with traditional analysis, without any sample pretreatment, facilitating continuous online monitoring in the field. The developed multielectrode system offers a feasible strategy for online in situ monitoring of surface water quality.

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During production, agricultural products are often susceptible to potential harm caused by residual traces of pesticides. Oxine-copper is a broad spectrum and efficient protective fungicide widely used in the production of fruits and vegetables. The present study was carried out to profile the dissipation behaviors and residues of oxine-copper on cucumber and watermelon using QuEChERS pretreatment and UPLC-MS/MS. Its storage stability and dietary risk assessment were also estimated. The method validation displayed good linearity (R 2 ≥ 0.9980), sensitivity (limits of quantification ≤0.01 mg/kg), and recoveries (75.5-95.8%) with relative standard deviations of 2.27-8.26%. According to first-order kinetics, the half-lives of oxine-copper in cucumber and watermelon were 1.77-2.11 and 3.57-4.68 d, respectively. The terminal residues of oxine-copper in cucumber and watermelon samples were within <0.01-0.264 and <0.01-0.0641 mg/kg, respectively. Based on dietary risk assessment, the estimated long-term dietary risk probability value of oxine-copper in cucumber and watermelon is 64.11%, indicating that long-term consumption of cucumber and watermelon contaminated with oxine-copper would not pose dietary risks to the general population. The results provide scientific guidance for the rational utilization of oxine-copper in field ecosystems of cucumber and watermelon.

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Background: Fatigue poses risks to occupational health and safety, affecting individuals' work efficiency, physical health, and social security, as well as human wellbeing and quality of life. Olfactory interventions, due to their low interference, are considered promising strategies for mitigating fatigue and reducing occupational health hazards. Objective: The objective of this review is to bridge the current gaps in the literature by conducting a scoping review of olfactory interventions on human alertness. It aims to explore their application in various occupational settings and to provide comprehensive and practical guidance for the practical application of olfactory interventions in mitigating fatigue and reducing occupational risks. Methods: The literature research was conducted in English using electronic databases such as Web of Science. Keywords related to scent and fatigue and the review followed PRISMA Extension for Scoping Reviews and PICO framework. Results: 28 studies were included in this work. Participant characteristics, fatigue measurement methods, and scent intervention methods, such as types of scents, intervention strategies, and scent presentation systems, are thoroughly investigated and discussed. Additionally, the study places a specific emphasis on the applications and research within the field of scent interventions for fatigue driving. Olfactory interventions have been applied to populations in various occupational fields, demonstrating beneficial effects on both physiological and psychological fatigue. Conclusions: Olfactory intervention is effective and promising for enhancing alertness and improving the occupational environment. To provide detailed and practical guidance for the actual application of olfactory intervention in fatigue relief and reducing occupational health and safety hazards, further research into the potential mechanisms, applications, and efficacy assessment systems of fatigue-related olfactory interventions is necessary.

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Morphology control is crucial in achieving high-performance organic solar cells (OSCs) and remains a major challenge in the field of OSC. Solid additive is an effective strategy to fine-tune morphology, however, the mechanism underlying isomeric solid additives on blend morphology and OSC performance is still vague and urgently requires further investigation. Herein, two solid additives based on pyridazine or pyrimidine as core units, M1 and M2, are designed and synthesized to explore working mechanism of the isomeric solid additives in OSCs. The smaller steric hindrance and larger dipole moment facilitate better π-π stacking and aggregation in M1-based active layer. The M1-treated all-small-molecule OSCs (ASM OSCs) obtain an impressive efficiency of 17.57%, ranking among the highest values for binary ASM OSCs, with 16.70% for M2-treated counterparts. Moreover, it is imperative to investigate whether the isomerization engineering of solid additives works in state-of-the-art polymer OSCs. M1-treated D18-Cl:PM6:L8-BO-based devices achieve an exceptional efficiency of 19.70% (certified as 19.34%), among the highest values for OSCs. The work provides deep insights into the design of solid additives and clarifies the potential working mechanism for optimizing the morphology and device performance through isomerization engineering of solid additives.

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Molecular mechanisms underlying the aging of Chinese Baijiu remained elusive. This study proposed the self-assembly behavior of amphiphilic molecules dominated by hydrogen bonds in Chinese Baijiu for the first time. The self-assembly degree of amphiphilic clusters gradually intensifies with the prolonged storage time of Baijiu, comprehensively characterized at both micro and macro levels. The results indicated that the blue-shift of the Raman hydrogen bond vibrational peak (about 11 cm-1 and 7 cm-1, respectively), the increase in viscosity (5.71% and 2.22%, respectively), and the rise in dielectric constant (95.63% and 94.99%, respectively) during the 17-year cellaring process of Strong-flavor Baijiu and Jiang-flavor Baijiu were consistent with the evolutionary trends observed in molecular dynamics simulations. The essential driving factors of cluster structure alteration of amphiphilic aroma substances in Chinese Baijiu during cellaring were demonstrated from molecular level. This study provided a research approach to comprehending the aging mechanism of Chinese Baijiu from the micro level.

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BACKGROUND: Emodin is a chemical compound found in traditional Chinese herbs. It possesses anti-inflammatory and many other pharmacological effects. Our previous study showed that emodin significantly alleviates the inflammation effect of severe acute pancreatitis (SAP). However, its poor solubility, high toxicity and limited pancreas retention time hinder its clinical application. PURPOSE: We aimed to prepare emodin nanocapsules with improved bioavailability to achieve the controlled release of emodin by targeting macrophages. Further, the mechanism of mannose-conjugated chitosan-coated lipid nanocapsules loaded with emodin (M-CS-E-LNC) in the treatment of SAP was explored. METHODS: M-CS-E-LNC were prepared by the phase inversion method with slight modification. The expression of inflammation mediators and the anti-inflammation efficacy of M-CS-E-LNC were examined by ELISA, IHC and IF in macrophage cells and LPS-induced SAP mice. IVIS spectrum imaging and HPLC were applied to explore the controlled release of M-CS-E-LNC in the pancreas. LC-MS/MS was performed for lipidomics analysis of macrophages. Moreover, a vector-based short hairpin RNA (shRNA) method was used to silence CTP1 gene expression in macrophage cells. RESULTS: The levels of inflammatory mediators in macrophages were markedly decreased after treatment with M-CS-E-LNC. The same anti-inflammation effects were detected in SAP mouse through the analysis of serum levels of amylase, TNF-α and IL-6. Importantly, M-CS-E-LNC allowed the emodin to selectively accumulate at pancreas and gastrointestinal tissues, thus exhibiting a targeted release. Mechanistically, the M-CS-E-LNC treatment group showed up-regulated expression of the carnitine palmitoyltransferase 1 (CPT1) protein which promoted intracellular long-chain fatty acid transport, thereby promoting the M2 phenotype polarization of macrophages. CONCLUSION: M-CS-E-LNC exhibited significantly improved bioavailability and water solubility, which translated to greater therapeutic effects on macrophage polarization. Our findings also demonstrate, for the first time, that CPT1 may be a new therapeutic target for SAP treatment.

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Fatigued driving threatens the safety of people's lives and property. Scent countermeasures offer minimal disruption and high efficacy, making them a promising approach. The aim of this study was to explore the application of scent countermeasures in alleviating fatigued driving. This study explored changes in EEG frequency bands (alpha, beta, theta, and gamma) and the activity of EEG metrics (R(α/ß), Rθ/(α+ß) and R(α+θ)/(α+ß)) in the temporal lobe during driving tasks, selected fatigued driving identifiers, and aided validation by investigating subjective fatigue with the Karolinska Sleepiness Scale (KSS). The EEG indicators all increased, with a significant increase in R(α/ß). R(α/ß) was combined with the KSS to explore the effects of three scents, peppermint, grapefruit, and lavender, on driving fatigue. The subjective questionnaire results indicated that all three scents significantly improved driving fatigue, with significantly lower levels of driving fatigue compared to the control group. The analysis of EEG signals revealed a significant decrease in R(α/ß) after the implementation of scent countermeasures. Moreover, R(α/ß) was found to be lower in all three odor intervention groups compared to the control group. All three scents were found to significantly alleviate driving fatigue. The grapefruit scent had a better timely effect in relieving driving fatigue and the lavender scent had a longer effectiveness. This study provides further exploration for the application of odor interventions to alleviate driving fatigue. This study provides a practical reference for drivers to use odors to avoid fatigue in order to improve road safety.

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Arctigenin, a natural product with diverse pharmacological activities, can inhibit cell proliferation and survival and has shown promising potential in cancer research. In this study, we designed a series of arctigenin derivatives with HDAC inhibitory activity based on the synergistic effects between HDAC inhibitors and arctigenin. Among them, compound B7 exhibited significantly higher antiproliferative activity in the MV411 cell line compared to the positive control, tucidinostat. Additionally, enzymatic activity testing was performed with compound B7. Further mechanistic studies indicated that compound B7 induced apoptosis through the Caspase-3 pathway in MV411 cells and enhanced histone acetylation levels in the MV411 cell line. These findings highlight the broad potential application of these arctigenin derivatives in cancer therapy.

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OBJECTIVE: There is a pronounced gap in knowledge regarding polygenic underpinnings of youth bipolar disorder (BD). This study aimed to compare polygenic risk scores (PRSs) in youth with BD, youth at high clinical and/or familial risk for BD (HR), and controls. METHOD: Participants were 344 youths of European ancestry (13-20 years old), including 136 youths with BD, 121 HR youths, and 87 controls. PRSs for BD, schizophrenia, major depressive disorder, and attention-deficit/hyperactivity disorder were constructed using independent genome-wide summary statistics from adult cohorts. Multinomial logistic regression was used to examine the association between each PRS and diagnostic status (BD vs HR vs controls). All genetic analyses controlled for age, sex, and 2 genetic principal components. RESULTS: The BD group showed significantly higher BD-PRS than the control group (odds ratio = 1.54, 95% CI = 1.13-2.10, p = .006), with the HR group numerically intermediate. BD-PRS explained 7.9% of phenotypic variance. PRSs for schizophrenia, major depressive disorder, and attention-deficit/hyperactivity disorder were not significantly different among groups. In the BD group, BD-PRS did not significantly differ in relation to BD subtype, age of onset, psychosis, or family history of BD. CONCLUSION: BD-PRS derived from adult genome-wide summary statistics is elevated in youth with BD. Absence of significant between-group differences in PRSs for other psychiatric disorders supports the specificity of BD-PRS in youth. These findings add to the biological validation of BD in youth and could have implications for early identification and diagnosis. To enhance clinical utility, future genome-wide association studies that focus specifically on early-onset BD are warranted, as are studies integrating additional genetic and environmental factors. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

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Depression is a major global health issue that urgently requires innovative and precise treatment options. In this context, saikosaponin has emerged as a promising candidate, offering a variety of therapeutic benefits that may be effective in combating depression. This review delves into the multifaceted potential of saikosaponins in alleviating depressive symptoms. We summarized the effects of saikosaponins on structural and functional neuroplasticity, elaborated the regulatory mechanism of saikosaponins in modulating key factors that affect neuroplasticity, such as inflammation, the hypothalamic-pituitary-adrenal (HPA) axis, oxidative stress, and the brain-gut axis. Moreover, this paper highlights existing gaps in current researches and outlines directions for future studies. A detailed plan is provided for the future clinical application of saikosaponins, advocating for more targeted researches to speed up its transition from preclinical trials to clinical practice.

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Response mechanism of the electrode is elucidated in terms of (hydrogen) phosphate accelerating oxidation of CoII to CoIII for the first time. Cyclic voltammetric techniques in conjunction with XRD, XPS and Raman characterizations have demonstrated unambiguously the response of cobalt (II) hydroxide electrode involves a phosphate and hydrogen ion dependent charge transfer process. Phosphate ions induce Co(OH)2 transformed into CoOOH within interlayer adsorption and restored the initial state after reduction. Meanwhile, the in common structural between Co(OH)2 and CoOOH prevents extensive structural convertibility upon cycling, result in the advantage of reversibility in phase transformation. Demonstrated sustainable technique offered the determination of phosphate with robust reproducibility (1000 cycles), long storage stability (6 months) and selectivity (potential interference: Cl-, NO3-, SO42- and HCO3-), achieving a detection limit of 5 × 10-8 M over a wide linear range up to 1.28 mM. Presented work provided insights into the unique selectivity towards phosphate in cobalt based sensors, which may inspire the rational design of Co(OH)2-based electrodes with superior electrochemical performance or extended applications.

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BACKGROUND: Systemic juvenile idiopathic arthritis (SJIA) is a form of childhood arthritis with clinical features such as fever, lymphadenopathy, arthritis, rash, and serositis. It seriously affects the growth and development of children and has a high rate of disability and mortality. SJIA may result from genetic, infectious, or autoimmune factors since the precise source of the disease is unknown. Our study aims to develop a genetic-based diagnostic model to explore the identification of SJIA at the genetic level. METHODS: The gene expression dataset of peripheral blood mononuclear cell (PBMC) samples from SJIA was collected from the Gene Expression Omnibus (GEO) database. Then, three GEO datasets (GSE11907-GPL96, GSE8650-GPL96 and GSE13501) were merged and used as a training dataset, which included 125 SJIA samples and 92 health samples. GSE7753 was used as a validation dataset. The limma method was used to screen differentially expressed genes (DEGs). Feature selection was performed using Lasso, random forest (RF)-recursive feature elimination (RFE) and RF classifier. RESULTS: We finally identified 4 key genes (ALDH1A1, CEACAM1, YBX3 and SLC6A8) that were essential to distinguish SJIA from healthy samples. And we combined the 4 key genes and performed a grid search as well as 10-fold cross-validation with 5 repetitions to finally identify the RF model with optimal mtry. The mean area under the curve (AUC) value for 5-fold cross-validation was greater than 0.95. The model's performance was then assessed once more using the validation dataset, and an AUC value of 0.990 was obtained. All of the above AUC values demonstrated the strong robustness of the SJIA diagnostic model. CONCLUSIONS: We successfully developed a new SJIA diagnostic model that can be used for a novel aid in the identification of SJIA. In addition, the identification of 4 key genes that may serve as potential biomarkers for SJIA provides new insights to further understand the mechanisms of SJIA.

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MAIN CONCLUSION: The oxidosqualene cyclases (OSCs) generating triterpenoid skeletons in Cyclocarya paliurus were identified for the first time, and two uridine diphosphate (UDP)-glycosyltransferases (UGTs) catalyzing the glycosylation of flavonoids were characterized. Cyclocarya paliurus, a native rare dicotyledonous plant in China, contains an abundance of triterpenoid saponins and flavonoid glycosides that exhibit valuable pharmaceutical effects in preventing hypertension, hyperlipidemia, and diabetes. However, the molecular mechanism explaining the biosynthesis of triterpenoid saponin and flavonoid glycoside in C. paliurus remains unclear. In this study, the triterpene content in different tissues and the expression pattern of genes encoding the key enzymes associated with triterpenoid saponin and flavonoid glycoside biosynthesis were studied using transcriptome and metabolome analysis. The eight upstream oxidosqualene cyclases (OSCs) involved in triterpenoid saponin biosynthesis were functionally characterized, among them CpalOSC6 catalyzed 2,3;22,23-dioxidosqualene to form 3-epicabraleadiol; CpalOSC8 cyclized 2,3-oxidosqualene to generate dammarenediol-II; CpalOSC2 and CpalOSC3 produced ß-amyrin and CpalOSC4 produced cycloartenol, while CpalOSC2-CpalOSC5, CpalOSC7, and CpalOSC8 all produced lanosterol. However, no catalytic product was detected for CpalOSC1. Moreover, two downstream flavonoid uridine diphosphate (UDP)-glycosyltransferases (UGTs) (CpalUGT015 and CpalUGT100) that catalyze the last step of flavonoid glycoside biosynthesis were functionally elucidated. These results uncovered the key genes involved in the biosynthesis of triterpenoid saponins and flavonoid glycosides in C. paliurus that could be applied to produce flavonoid glycosides and key triterpenoid saponins in the future via a synthetic strategy.

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