N-p-coumaroyloctopamine ameliorates hepatic glucose metabolism and oxidative stress involved in a PI3K/AKT/GSK3ß pathway.

Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic ß-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects and mechanisms of action of N-p-coumaroyloctopamine (N-p-CO) in vitro and in vivo. N-p-CO exhibited high antioxidant activity, as indicated by the increased activity of SOD, GSH and GSH-Px in HL-7702 cells induced by both high glucose (HG) and palmitic acid (PA). N-p-CO treatment significantly augmented glucose uptake and glycogen synthesis in HG/PA-treated HL-7702 cells. Moreover, administration of N-p-CO in diabetic mice induced by both high-fat diet (HFD) and streptozotocin (STZ) not only significantly increased the antioxidant levels of GSH-PX, SOD and GSH, but also dramatically alleviated hyperglycemia and hepatic glucose metabolism in a dose-dependent manner. More importantly, N-p-CO upregulated the expressions of PI3K, AKT and GSK3ß proteins in both HG/PA-induced HL-7702 cells and HFD/STZ-induced mice. These findings clearly suggest that N-p-CO exerts anti-hypoglycemic and anti-oxidant effects, most probably via the regulation of a PI3K/AKT/GSK3ß signaling pathway. Thus, N-p-CO may have high potentials as a new candidate for the prevention and treatment of diabetes.

Binasal Quadrantanopia: A Rare Visual Field Defect Poses Challenges in Terms of Lesion Localization.

Binasal quadrantanopia is a rare type of visual field defect characteristic of vision loss in either the upper or lower quadrants of both nasal visual fields. The affected individuals often exhibit impairments in peripheral vision, leading to difficulties in various daily activities such as navigation, object recognition, and hazard avoidance. The consequences of binasal quadrantanopia can be profound, affecting the individual's quality of life and functional independence. However, due to its atypical presentation and overlapping clinical features with other visual field defects, accurately pinpointing the lesion's precise location for further management becomes a complex task. Here, we present an unusual case of binasal quadrantanopia caused by bilateral anterior ischemic optic neuropathy (AION) and aim to explore the unique characteristics, etiology, and diagnostic approaches associated with binasal quadrantanopia, shedding light on the challenges encountered in lesion localization.

Comparative chemical profiling of leaf essential oils from Cinnamomum kanehirae and related species using steam distillation and solvent extraction: Implications for plant-based classification.

Cinnamomum kanehirae Hayata, belonging to Lauraceae family, is an indigenous and endangered species of considerable economic importance in Taiwan. It plays a crucial role as the host for the economically valuable saprotrophic fungus, Taiwanofungus camphorates. However, accurate species identification poses a challenge due to the similarity in morphological features and frequent natural hybridization with closely related species. Acquiring high-quality and pure leaf oils becomes imperative for precise species identification and producing superior goods. In this study, our objective was to establish methodologies for analyzing the chemical composition of leaf essential oils and subsequently apply this knowledge to differentiate among three Cinnamomum species. Gas chromatography-mass spectrometry (GC/MS) was employed to scrutinize the chemical makeup of leaf essential oils from three closely related species: C. kanehirae, C. micranthum, and C. camphora. We utilized Steam Distillation (SD) and steam distillation-solvent extraction (SDSE) methods, with the SDSE-Hexane approach chosen for optimization, enhancing extraction efficiency and ensuring essential oil purity. Through the SDSE-Hexane method, we identified seventy-four compounds distributed across three major classes: monoterpenes hydrocarbons (0.0-7.0 %), oxygenated monoterpenes (3.8-90.9 %), sesquiterpenes hydrocarbons (0.0-28.3 %), and oxygenated sesquiterpenes (1.6-88.1 %). Our findings indicated the presence of more than one chemotype in both C. kanehirae and C. camphora, whereas no specific chemotype could be discerned in C. micranthum. Furthermore, clustering based on chemotypes allowed for the differentiation of samples from the three species. Notably, we demonstrated that the chemical compositions of grafted C. kanehirae remained largely unaffected by the rootstock. Conversely, natural hybrids between C. kanehirae and C. camphora exhibited profiles more closely aligned with C. kanehirae. The optimized extraction method and the chemotype-based classification system established in this study present valuable tools for essential oil preparation, species identification, and further exploration into the genetic variation of Cinnamomum.

A novel non-invasive embryo evaluation method (NICS-Timelapse) with enhanced predictive precision and clinical impact.

The selection of the finest possible embryo in in-vitro fertilization (IVF) was crucial and revolutionary, particularly when just one embryo is transplanted to lessen the possibility of multiple pregnancies. However, practical usefulness of currently used methodologies may be constrained. Here, we established a novel non-invasive embryo evaluation method that combines non-invasive chromosomal screening (NICS) and Timelapse system along with artificial intelligence algorithms. With an area under the curve (AUC) of 0.94 and an accuracy of 0.88, the NICS-Timelapse model was able to predict blastocyst euploidy. The performance of the model was further evaluated using 75 patients in various clinical settings. The clinical pregnancy and live birth rates of embryos predicted by the NICS-Timelapse model, showing that embryos with higher euploid probabilities were associated with higher clinical pregnancy and live birth rates. These results demonstrated the NICS-Timelapse model's significantly wider application in clinical IVF due to its excellent accuracy and noninvasiveness.

SF-36v2 and FACIT-Fatigue quality of life improvements with organ-specific SELENA-SLEDAI response and belimumab treatment in patients with systemic lupus erythematosus.

OBJECTIVE: Explore organ-specific SLE burden by assessing health-related quality of life (HRQoL) and fatigue changes associated with Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ system response (score improvement) and belimumab treatment. METHODS: Data from four phase III belimumab trials were pooled for post hoc analysis (GSK Study 217382): BLISS-52 (NCT00424476), BLISS-76 (NCT00410384), BLISS-SC (NCT01484496) and EMBRACE (NCT01632241). Patients with baseline organ system involvement were classed as organ system responders if SELENA-SLEDAI scores for that organ system decreased at any post-baseline visit. HRQoL (36-Item Short Form Health Survey version 2 (SF-36v2)) and fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue)) changes over 52 weeks were compared between organ system responders and non-responders, and separately between belimumab versus placebo treatment arms among organ system responders. Group-level differences were compared using analysis of variance; differences were interpreted using published group-level minimal important difference (MID). RESULTS: In these post hoc analyses, musculoskeletal and mucocutaneous organ system responders had greater SF-36v2 improvements than non-responders across most SF-36v2 domains, but differences were largely MID), with FACIT-Fatigue also improving >MID for renal responders receiving belimumab. CONCLUSIONS: SLE disease burden differs with the organ system(s) involved. While these analyses are limited by mutual inclusivity of organ system groupings, differing patient numbers between groups and small numbers in some groups, they suggest that mucocutaneous and musculoskeletal organ system response improves SF-36v2 domain scores; cardiovascular and respiratory organ system response may meaningfully improve fatigue; and belimumab may offer additional HRQoL or fatigue benefits beyond standard therapy for musculoskeletal and renal responders.

Artificial intelligence-based tools with automated segmentation and measurement on CT images to assist accurate and fast diagnosis in acute pancreatitis.

PURPOSE: To develop an artificial intelligence (AI) tool with automated pancreas segmentation and measurement of pancreatic morphological information on CT images to assist improved and faster diagnosis in acute pancreatitis. METHODS: This study retrospectively contained 1124 patients suspected for AP and received non-contrast and enhanced abdominal CT examination between September 2013 to September 2022. Patients were divided into training (N = 688), validation (N = 145), testing dataset (N = 291, N = 104 for normal pancreas, N = 98 for AP, N = 89 for AP complicated with PDAC (AP&PDAC)). A model based on convolutional neural network (MSAnet) was developed. The pancreas segmentation and measurement were performed via eight open-source models and MSAnet based tools, and the efficacy was evaluated using Dice similarity coefficient (DSC) and Intersection over union (IoU). The DSC and IoU for patients with different ages were also compared. The outline of tumor and edema in the AP and were segmented by clustering. The diagnostic efficacy for radiologists with or without the assistance of MSAnet tool in AP and AP&PDAC was evaluated using receiver operation curve and confusion matrix. RESULTS: Among all models, MSAnet based tool showed best performance on the training and validation dataset, and had high efficacy on testing dataset. The performance was age-affected. With assistance of the AI tool, the diagnosis time was significantly shortened by 26.8% and 32.7% for junior and senior radiologists, respectively. The area under curve in diagnosis of AP was improved from 0.91 to 0.96 for junior radiologist and 0.98 to 0.99 for senior radiologist. In AP&PDAC diagnosis, AUC was increased from 0.85 to 0.92 for junior and 0.97 to 0.99 for senior. CONCLUSION: MSAnet based tools showed good pancreas segmentation and measurement performance, which help radiologists improve diagnosis efficacy and workflow in both AP and AP with PDAC conditions. ADVANCES IN KNOWLEDGE: This study developed an AI tool with automated pancreas segmentation and measurement and provided evidence for AI tool assistance in improving the workflow and accuracy of AP diagnosis.

Anticancer efficacy triggered by synergistically modulating the homeostasis of anions and iron: Design, synthesis and biological evaluation of dual-functional squaramide-hydroxamic acid conjugates.

Targeting the homeostasis of anions and iron has emerged as a promising therapeutic approach for the treatment of cancers. However, single-targeted agents often fall short of achieving optimal treatment efficacy. Herein we designed and synthesized a series of novel dual-functional squaramide-hydroxamic acid conjugates that are capable of synergistically modulating the homeostasis of anions and iron. Among them, compound 16 exhibited the most potent antiproliferative activity against a panel of selected cancer cell lines, and strong in vivo anti-tumor efficacy. This compound effectively elevated lysosomal pH through anion transport, and reduced the levels of intracellular iron. Compound 16 could disturb autophagy in A549 cells and trigger robust apoptosis. This compound caused cell cycle arrest at the G1/S phase, altered the mitochondrial function and elevated ROS levels. The present findings clearly demonstrated that synergistic modulation of anion and iron homeostasis has high potentials in the development of promising chemotherapeutic agents with dual action against cancers.

Advances in Nanotechnology for Enhancing the Solubility and Bioavailability of Poorly Soluble Drugs.

This manuscript offers a comprehensive overview of nanotechnology's impact on the solubility and bioavailability of poorly soluble drugs, with a focus on BCS Class II and IV drugs. We explore various nanoscale drug delivery systems (NDDSs), including lipid-based, polymer-based, nanoemulsions, nanogels, and inorganic carriers. These systems offer improved drug efficacy, targeting, and reduced side effects. Emphasizing the crucial role of nanoparticle size and surface modifications, the review discusses the advancements in NDDSs for enhanced therapeutic outcomes. Challenges such as production cost and safety are acknowledged, yet the potential of NDDSs in transforming drug delivery methods is highlighted. This contribution underscores the importance of nanotechnology in pharmaceutical engineering, suggesting it as a significant advancement for medical applications and patient care.

Baseline immunoglobulin G and immune function in non-Hodgkin lymphoma: a retrospective analysis.

Introduction: Non-Hodgkin's lymphoma (NHL) encompasses a diverse group of lymphoma subtypes with a wide range in disease course. Previous studies show that hypogammaglobulinemia in treatment-naïve patients is associated with poorer survival in high grade B-cell non-Hodgkin's lymphomas, though it is not known how this applies across all B-cell lymphoid malignancies. Methods: We conducted a retrospective study of immunoglobulin levels and clinical outcomes including survival, hospitalization, and infection rates in patients diagnosed with B-cell non-Hodgkin lymphomas of all grades at our institution. Results: Two-hundred twenty-three adults (aged = 18 years) with available pre-treatment IgG levels were selected, with hypogammaglobulinemia defined as IgG< 500 mg/mL. For this analysis, we grouped DLBCL (n=90), Primary CNS (n=5), and Burkitt lymphoma (n=1) together as high-grade, while CLL (n=52), mantle cell (n=20), marginal zone (n=25), follicular (n=21), and Waldenstrom macroglobulinemia (n=5) were low-grade. The incidence of hypogammaglobulinemia in our cohort of both high and low-grade lymphoma patients was 13.5% (n=30). Across all NHL subtypes, individuals with baseline IgG< 500 mg/dL showed an increased rate of hospitalization (4.453, CI: 1.955-10.54, p= 0.0005) and higher mortality (3.325, CI: 1.258, 8.491, p= 0.013), yet no association in number of infections when compared with those with IgG=500 mg/dL. There was a higher hospitalization rate (3.237, CI: 1.77-6.051, p=0.0017) in those with high-grade lymphoma with hypogammaglobulinemia when compared with low-grade. There was no statistically significant difference in individuals who were alive after three years in those with baseline IgG<500 mg/dL. Discussion: Our study is the first to analyze incidence of hypogammaglobulinemia at the time of diagnosis of NHL as a potential biomarker of interest for future outcomes including hospitalization and infection.

Construction of a novel fluorescent probe for sensitive determination of glyphosate in food and imaging living cells.

Glyphosate is a widely used broad-spectrum herbicide in agriculture and horticulture to control a variety of weeds and undesirable plants. However, the excessive use of glyphosate has raised a number of environmental and human health concerns. It is urgent to develop tools to detect glyphosate. Herein, a novel dual-signal probe CCU-Cu2+ was designed and synthesized on the basis of CCU. CCU exhibited excellent selectivity and great sensitivity for Cu2+ which were based on both fluorescence "turn-off" reaction and comparative color visualisation methods. Due to the strong chelating ability of glyphosate on Cu2+, the CCU-Cu2+ complex was applied to glyphosate detection in practical samples. The experimental results in vitro showed that the CCU-Cu2+ complex was highly selective and rapid, with a low detection limit (1.6 µM), and could be recognised by the naked eye in the detection of glyphosate. Based on the excellent properties of the CCU-Cu2+ complex, we also constructed a smartphone-assisted detection sensing system for glyphosate detection, which has the advantages of precision, sensitivity, and high interference immunity. Moreover, the CCU-Cu2+ complex was also successfully employed for exogenous glyphosate imaging in living cells. These characteristics demonstrated that CCU-Cu2+ holds significant potential for detection and imaging of glyphosate in bio-systems.

Human papillomavirus infection and the risk of cancer at specific sites other than anogenital tract and oropharyngeal region: an umbrella review.

BACKGROUND: Despite numerous studies having evaluated the associations between human papillomavirus (HPV) infection and risk of specific cancers other than anogenital tract and oropharyngeal, the findings are inconsistent and the quality of evidence has not been systematically quantified. We aimed to summarise the existing evidence as well as to evaluate the strength and credibility of these associations. METHODS: We conducted an umbrella review of systematic reviews and meta-analyses of observational studies. PubMed, EMBASE, and Web of Science were searched from inception to March 2024. Studies with systematic reviews and meta-analyses that examined associations between HPV or HPV-associated genotypes infection and specific cancers were eligible for this review. The quality of the methodology was evaluated using A Measurement Tool to Assess systematic Reviews (AMSTAR). The credibility of the evidence was assessed using GRADE. The protocol was preregistered with PROSPERO (CRD42023439070). FINDINGS: The umbrella review identified 31 eligible studies reporting 87 associations with meta-analytic estimates, including 1191 individual studies with 336,195 participants. Of those, 29 (93.5%) studies were rated as over moderate quality by AMSTAR. Only one association indicating HPV-18 infection associated with an increased risk of breast cancer (odds ratio [OR] = 3.48, 95% confidence interval [CI] = 2.24-5.41) was graded as convincing evidence. There were five unique outcomes identified as highly suggestive evidence, including HPV infection increased the risk of oral squamous cell carcinoma (OR = 7.03, 95% CI = 3.87-12.76), oesophageal cancer (OR = 3.32, 95% CI = 2.54-4.34), oesophageal squamous cell carcinoma (OR = 2.69, 95% CI = 2.05-3.54), lung cancer (OR = 3.60, 95% CI = 2.59-5.01), and breast cancer (OR = 6.26, 95% CI = 4.35-9.00). According to GRADE, one association was classified as high, indicating that compared with the controls in normal tissues, HPV infection was associated with an increased risk of breast cancer. INTERPRETATION: The umbrella review synthesised up-to-date observational evidence on HPV infection with the risk of breast cancer, oral squamous cell carcinoma, oesophageal cancer, oesophageal squamous cell carcinoma, and lung cancer. Further larger prospective cohort studies are needed to verify the associations, providing public health recommendations for prevention of disease. FUNDING: National Key Research and Development Program of China, Natural Science Foundation of China, Outstanding Scientific Fund of Shengjing Hospital of China Medical University, and 345 Talent Project of Shengjing Hospital of China Medical University.

Gut Microbiome-Serum Metabolism Revealed the Allergenicity of Ferulic Acid Combined with Glucose-Modified ß-Lactoglobulin.

A novel strategy combining ferulic acid and glucose was proposed to reduce ß-lactoglobulin (BLG) allergenicity and investigate whether the reduction in allergenicity was associated with gut microbiome and serum metabolism. As a result, the multistructure of BLG changed, and the modified BLG decreased significantly the contents of IgE, IgG, IgG1, and mMCP-1 in serum, improved the diversity and structural composition of gut microbiota, and increased the content of short-chain fatty acids (SCFAs) in allergic mice. Meanwhile, allergic mice induced by BLG affected arachidonic acid, tryptophan, and other metabolic pathways in serum, the modified BLG inhibited the production of metabolites in arachidonic acid metabolism pathway and significantly increased tryptophan metabolites, and this contribution helps in reducing BLG allergenicity. Overall, reduced allergenicity of BLG after ferulic acid was combined with glucose modification by regulating gut microbiota, the metabolic pathways of arachidonic acid and tryptophan. The results may offer new thoughts alleviating the allergy risk of allergenic proteins.

Itaconate protects ferroptotic neurons by alkylating GPx4 post stroke.

Neuronal ferroptosis plays a key role in neurologic deficits post intracerebral hemorrhage (ICH). However, the endogenous regulation of rescuing ferroptotic neurons is largely unexplored. Here, we analyzed the integrated alteration of metabolomic landscape after ICH using LC-MS and MALDI-TOF/TOF MS, and demonstrated that aconitate decarboxylase 1 (Irg1) and its product itaconate, a derivative of the tricarboxylic acid cycle, were protectively upregulated. Deficiency of Irg1 or depletion of neuronal Irg1 in striatal neurons was shown to exaggerate neuronal loss and behavioral dysfunction in an ICH mouse model using transgenic mice. Administration of 4-Octyl itaconate (4-OI), a cell-permeable itaconate derivative, and neuronal Irg1 overexpression protected neurons in vivo. In addition, itaconate inhibited ferroptosis in cortical neurons derived from mouse and human induced pluripotent stem cells in vitro. Mechanistically, we demonstrated that itaconate alkylated glutathione peroxidase 4 (GPx4) on its cysteine 66 and the modification allosterically enhanced GPx4's enzymatic activity by using a bioorthogonal probe, itaconate-alkyne (ITalk), and a GPx4 activity assay using phosphatidylcholine hydroperoxide. Altogether, our research suggested that Irg1/itaconate-GPx4 axis may be a future therapeutic strategy for protecting neurons from ferroptosis post ICH.

Iodine Status and Its Influencing Factors in Hospitalized and Healthy Preschool-Age Children.

Iodine is a trace element necessary for synthesizing thyroid hormones. It is especially crucial for the neurodevelopment and intellectual development of children. Preschool-age children admitted to the hospital tend to have more fragile physical and mental health, but few studies demonstrate their iodine status. Our study aimed to investigate the iodine status of hospitalized and healthy preschool-age children and to explore the factors influencing them. From January to December 2021, 426 children aged 3-6 years were admitted to the respiratory department for pneumonia, bronchopneumonia, or bronchiectasis, but they could eat normally and were recruited as hospitalized children. Six hundred ten healthy children aged 3-6 years were included. We collected anthropometric measurements and urine samples from hospitalized and healthy preschool-age children, and iodine status was assessed through urinary iodine concentration (UIC) and urinary iodine/creatinine ratio (UI/Cr). UIC was 40.1 and 166.1 µg/L for hospitalized and healthy preschool-age children, respectively (P < 0.001). Urinary creatinine concentration (UCr) was 0.2 and 0.8 g/L for hospitalized and healthy preschool-age children, respectively (P < 0.001). UIC decreased with increasing height z-scores in hospitalized children (Spearman's rho = -0.11, P = 0.022). A significantly increased risk of UIC < 100 µg/L was found in hospitalized children (OR = 9.1 (6.8, 12.2), P < 0.001) when compared to healthy children. In conclusion, hospitalized preschool-age children are likelier to have iodine insufficiency than healthy preschool-age children, especially those with good linear growth. Measures should be implemented to ensure adequate iodine intake of preschool-age children during hospitalization to avoid affecting their intellectual and physical development. Due to lower UCr in hospitalized children, creatinine is not appropriate for assessing iodine status in hospitalized children.

Electrical Double-Layer Transistors Comprising Block Copolymer Electrolytes for Low-Power-Consumption Photodetectors.

Electrical double-layer transistors (EDLTs) have received extensive research attention owing to their exciting advantages of low working voltage, high biocompatibility, and sensitive interfacial properties in ultrasensitive portable sensing applications. Therefore, it is of great interest to reduce photodetectors' operating voltage and power consumption by utilizing photo-EDLT. In this study, a series of block copolymers (BCPs) of poly(4-vinylpyridine)-block-poly(ethylene oxide) (P4VP-b-PEO) with different compositions were applied to formulate polyelectrolyte with indigo carmine salt in EDLT. Accordingly, PEO conduces ion conduction in the BCP electrolyte and enhances the carrier transport capability in the semiconducting channel; P4VP boosts the photocurrent by providing charge-trapping sites during light illumination. In addition, the severe aggregation of PEO is mitigated by forming a BCP structure with P4VP, enhancing the stability and photoresponse of the photo-EDLT. By optimizing the BCP composition, EDLT comprising P4VP16k-b-PEO5k and indigo carmine provides the highest specific detectivity of 2.1 × 107 Jones, along with ultralow power consumptions of 0.59 nW under 450 nm light illumination and 0.32 pW under dark state. The results indicate that photo-EDLT comprising the BCP electrolyte is a practical approach to reducing phototransistors' operating voltage and power consumption.

Acute resistance exercise combined with whole body vibration and blood flow restriction: Molecular and neurocognitive effects in late-middle-aged and older adults.

Limited research exists regarding the effects of resistance exercise (RE) combined with whole body vibration (WBV), blood flow restriction (BFR), or both on the neuropsychological performance of working memory (WM) in late-middle-aged and older adults and regarding the physiological mechanisms underlying this effect. This study thus explored the acute molecular and neurophysiological mechanisms underlying WM performance following RE combined with WBV, BFR, or both. Sixty-six participants were randomly assigned into a WBV, BFR, or WBV + BFR group. Before and after the participants engaged in a single bout of isometric RE combined with WBV, BFR, or both, this study gathered data on several neurocognitive measures of WM performance, namely, accuracy rate (AR), reaction time (RT), and brain event-related potential (specifically P3 latency and amplitude), and data on biochemical indices, such as the levels of insulin-like growth factor-1 (IGF-1), norepinephrine (NE), and brain-derived neurotrophic factor (BDNF). Although none of the RE modalities significantly affected RTs and P3 latencies, ARs and P3 amplitudes significantly improved in the WBV and WBV + BFR groups. The WBV + BFR group exhibited greater improvements than the WBV group did. Following acute RE combined with WBV, BFR, or both, IGF-1 and NE levels significantly increased in all groups, whereas BDNF levels did not change. Crucially, only the changes in NE levels were significantly correlated with improvements in ARs in the WBV + BFR and WBV groups. The findings suggest that combining acute RE with WBV, BFR, or both could distinctively mitigate neurocognitive decline in late-middle-aged and older adults.

Untargeted metabolomics based on ultra-high performance liquid chromatography-mass spectrometry/MS reveals the lipid-lowering mechanism of taurine in hyperlipidemia mice.

Introduction: Taurine has a prominent lipid-lowering effect on hyperlipidemia. However, a comprehensive analysis of the effects of taurine on endogenous metabolites in hyperlipidemia has not been documented. This study aimed to explore the impact of taurine on multiple metabolites associated with hyperlipidemia. Methods: The hyperlipidemic mouse model was induced by high-fat diet (HFD). Taurine was administered via oral gavage at doses of 700 mg/kg/day for 14 weeks. Evaluation of body weight, serum lipid levels, and histopathology of the liver and adipose tissue was performed to confirm the lipid-lowering effect of taurine. Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabonomics analyses of serum, urine, feces, and liver, coupled with multivariate data analysis, were conducted to assess changes in the endogenous metabolites. Results and discussion: Biochemical and histological examinations demonstrated that taurine administration prevented weight gain and dyslipidemia, and alleviated lipid deposition in the liver and adipose tissue in hyperlipidemic mice. A total of 76 differential metabolites were identified by UPLC-MS-based metabolomics approach, mainly involving BAs, GPs, SMs, DGs, TGs, PUFAs and amino acids. Taurine was found to partially prevent HFDinduced abnormalities in the aforementioned metabolites. Using KEGG database and MetaboAnalyst software, it was determined that taurine effectively alleviates metabolic abnormalities caused by HFD, including fatty acid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, diacylglycerol metabolism, amino acid metabolism, bile acid and taurine metabolism, taurine and hypotaurine metabolism. Moreover, DGs, GPs and SMs, and taurine itself may serve as active metabolites in facilitating various anti-hyperlipidemia signal pathways associated with taurine. This study provides new evidence for taurine to prevent hyperlipidemia.

Orexin Neurons to Sublaterodorsal Tegmental Nucleus Pathway Prevents Sleep Onset REM Sleep-Like Behavior by Relieving the REM Sleep Pressure.

Proper timing of vigilance states serves fundamental brain functions. Although disturbance of sleep onset rapid eye movement (SOREM) sleep is frequently reported after orexin deficiency, their causal relationship still remains elusive. Here, we further study a specific subgroup of orexin neurons with convergent projection to the REM sleep promoting sublaterodorsal tegmental nucleus (OXSLD neurons). Intriguingly, although OXSLD and other projection-labeled orexin neurons exhibit similar activity dynamics during REM sleep, only the activation level of OXSLD neurons exhibits a significant positive correlation with the post-inter-REM sleep interval duration, revealing an essential role for the orexin-sublaterodorsal tegmental nucleus (SLD) neural pathway in relieving REM sleep pressure. Monosynaptic tracing reveals that multiple inputs may help shape this REM sleep-related dynamics of OXSLD neurons. Genetic ablation further shows that the homeostatic architecture of sleep/wakefulness cycles, especially avoidance of SOREM sleep-like transition, is dependent on this activity. A positive correlation between the SOREM sleep occurrence probability and depression states of narcoleptic patients further demonstrates the possible significance of the orexin-SLD pathway on REM sleep homeostasis.

The effect of supplementing with Saccharomyces boulardii on bismuth quadruple therapy for eradicating Helicobacter pylori: a systematic review and meta-analysis of randomized controlled trials.

Background and objective: It remains uncertain if the addition of Saccharomyces boulardii (S. boulardii) to bismuth quadruple therapy (BQT) recommended in the current guidelines can enhance the Helicobacter pylori (H. pylori) eradication rate and decrease the incidence of adverse events. We therefore conducted a meta-analysis of randomized controlled trials (RCTs) to address this issue. Methods: We performed comprehensive searches in PubMed, Embase, Web of Science, and Cochrane library databases from the inception of the databases through to November 1, 2023. A meta-analysis was conducted to determine the pooled relative risk (RR) with 95% confidence intervals (CI) using a random-effects model. We utilized the revised Cochrane Risk of Bias Tool to assess the risk of bias of included studies. Results: A total of six RCTs (1,404 patients) included in this meta-analysis. The results of the intention-to-treat analysis showed that the combination of S. boulardii with BQT had a higher eradication rate than BQT alone (87.0% versus 83.3%), with a pooled RR of 1.05 (95% CI: 1.00-1.10, p = 0.03). In the per-protocol analysis, however, there was no statistical significance between the two groups in the eradication rate (93.7% versus 91.0%, RR = 1.03, 95% CI: 1.00-1.06, p = 0.07). The combination of S. boulardii and BQT had a significantly lower rate of overall adverse events (22% vs. 39%, RR = 0.56, 95% CI: 0.44-0.70, p < 0.00001), diarrhea (7.9% vs. 25.7%, RR = 0.29, 95% CI: 0.17-0.48, p < 0.00001), constipation (2.9% vs. 8.4%, RR = 0.35, 95% CI: 0.14-0.88, p = 0.03) and abdominal distention (4.9% vs. 12.7%, RR = 0.41, 95% CI: 0.23-0.72, p = 0.002) than BQT alone. For the assessment of risk of bias, five studies were deemed to have some concerns, while one study was judged to have a low risk. Conclusion: Current evidence suggests that supplementation with S. boulardii in BQT may not have a major effect on the H. pylori eradication rate, but significantly reduces the incidence of overall adverse events, diarrhea, abdominal distention and constipation. Combining S. Boulardii with BQT can help alleviate symptoms, potentially improving patient adherence. Systematic review registration: https://osf.io/n9z7c.

TempEasy 3D Hydrogel Coculture System Provides Mechanistic Insights into Prostate Cancer Bone Metastasis.

Patients diagnosed with advanced prostate cancer (PCa) often experience incurable bone metastases; however, a lack of relevant experimental models has hampered the study of disease mechanisms and the development of therapeutic strategies. In this study, we employed the recently established Temperature-based Easy-separable (TempEasy) 3D cell coculture system to investigate PCa bone metastasis. Through coculturing PCa and bone cells for 7 days, our results showed a reduction in PCa cell proliferation, an increase in neovascularization, and an enhanced metastasis potential when cocultured with bone cells. Additionally, we observed increased cell proliferation, higher stemness, and decreased bone matrix protein expression in bone cells when cocultured with PCa cells. Furthermore, we demonstrated that the stiffness of the extracellular matrix had a negligible impact on molecular responses in both primary (PCa cells) and distant malignant (bone cells) sites. The TempEasy 3D hydrogel coculture system is an easy-to-use and versatile coculture system that provides valuable insights into the mechanisms of cell-cell communication and interaction in cancer metastasis.