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Background: A newly identified type of cell death due to intracellular copper accumulation is known as cuproptosis and RNA methylation is a post-transcriptional modification mechanism, both of which perform vital roles in the immune microenvironment of colorectal cancer (CRC), but the link between the two needs more research., Methods: TCGA database provided RNA-seq data and details clinically of CRC samples. Cuproptosis-related RNA methylation regulators (CRRMRs) were identified by correlation analysis. We screened 6 CRRMRs for prognostic model construction by employing LASSO-Cox regression analysis and calculated risk scores by CRRMRs (CuMS). GSE39582 and GSE38832 cohort were used as external validation sets. This research concentrated on the connection between the prognostic model and somatic mutation, anti-cancer drug sensitivity, immune infiltration, immune checkpoint expression. In addition, we investigated the differential expression of YTHDC2 in epithelial cell subpopulations by single-cell analysis with GSE166555, calculated cuproptosis scores and performed pathway enrichment. In vitro experiments were performed to explore the consequences of knockdown of YTHDC2 on CRC cell proliferation and migration, as well as changes in CRC cell viability in response to elesclomol after knockdown of YTHDC2. In vivo experiments, we constructed the cell line-derived xenograft model to further validate the results of the in vitro experiments., Results: The prognosis of CRC can be predicted by CuMS, which GSE39582 and GSE38832 confirmed. Two CuMS groups showed different tumor mutation burden (TMB) and immune infiltration. CuMS was connected to emerging immune checkpoints CD47 and PVR, therefore, it can be clinically complementary to TMB and microsatellite instability (MSI) status. In single-cell analysis, a subpopulation of epithelial cells with high YTHDC2 expression had a high cuproptosis score. In vitro experiments, knocking down YTHDC2 promoted cell proliferation and migration in CRC, and weaken the inhibitory effect of elesclomol and elesclomol-Cu on cell viability, which in vivo experiments validated., Conclusion: We developed a prognostic model constructed by 6 CRRMRs to assess overall survival and immune microenvironment of CRC patients. YTHDC2 might regulate cuproptosis in multiple ways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

High pressure processing is a safe and green novel non-thermal processing technique for modulating food protein aggregation behavior. However, the systematic relationship between high pressure processing conditions and protein deaggregation has not been sufficiently investigated. Major royal jelly proteins, which are naturally highly fibrillar aggregates, and it was found that the pressure level and exposure time could significantly promote protein deaggregation. The 100-200 MPa treatment favoured the deaggregation of proteins with a significant decrease in the sulfhydryl group content. Contrarily, at higher pressure levels (>400 MPa), the exposure time promoted the formation of disordered agglomerates. Notably, the inter-conversion of α-helix and β-strands in major royal jelly proteins after high pressure processing eliminates the solvent-free cavities inside the aggregates, which exerts a 'collapsing' effect on the fibrillar aggregates. Furthermore, the first machine learning model of the high pressure processing conditions and the protein deaggregation behaviour was developed, which provided digital guidance for protein aggregation regulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study explores the impact of postharvest storage temperatures (4 °C and 25 °C) on starch metabolism and textural attributes of glutinous lotus root. While starch metabolism is a well-known factor influencing texture, changes in powdery and sticky qualities have remained unexplored. Our research reveals that storing lotus roots at 4 °C delays water dissipation, amylopectin reduction, and the decline in textural elements such as hardness, adhesiveness, springiness, gumminess, and resilience. Lower temperatures postpone amylopectin reduction and sugar interconversion, thereby preserving the sticky texture. Additionally, they suppress starch formation, delay starch metabolism, and elevate the expression of genes involved in starch metabolism. The correlation between gene expression and root texture indicates the critical role of gene regulation in enzyme activity during storage. Overall, low-temperature storage extends lotus root preservation by regulating metabolite content, enzyme activities, and the corresponding genes involved in starch metabolism, preserving both intrinsic and external root quality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Depression and suicidal ideation often co-occur in children and adolescents, yet they possess distinct characteristics. This study sought to identify the different related factors associated with depression and suicidal ideation., Methods: A nationwide cross-sectional survey collected data from Chinese children and adolescents aged 8 to 18 (N = 160,962; 48.91 % girls). The survey included inquiries about demographics, depression, suicidal ideation, anxiety, perceived stress, academic burnout, internet addiction, non-suicidal self-injury, bullying, and being bullied. Fifteen machine learning algorithms were conducted to identify the different related factors associated with depression and suicidal ideation. Additionally, we conducted external validation on an independent sample of 1,812,889 children and adolescents., Results: Our findings revealed seven related factors linked to depression and six associated with suicidal ideation, with average accuracy rates of 86.86 % and 85.82 %, respectively. For depression, the most influential factors were anxiety, perceived stress, academic burnout, internet addiction, non-suicidal self-injury, experience of bullying, and age. Similarly, anxiety, non-suicidal self-injury, perceived stress, internet addiction, academic burnout, and age emerged as paramount factors for suicidal ideation. Moreover, these related factors showed notable variations in their predictive capacities for depression and suicidal ideation across different subgroups., Conclusion: Anxiety emerged as the predominant shared factor for both depression and suicidal ideation, whereas the other related factors displayed distinct predictive patterns for each condition. These findings highlight the critical need for tailored strategies from public mental health service providers and policymakers to address the pressing concerns of depression and suicidal ideation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: We aimed to examine whether positive and negative coping styles mediated the influences of childhood trauma on NSSI or depressive severity in adolescents with major depressive disorder (MDD)., Methods: The Children's Depression Inventory (CDI), the Ottawa Self-Injury Inventory Chinese Revised Edition (OSIC), the short-form Childhood Trauma Questionnaire (CTQ-SF), and the Simplified Coping Style Questionnaire (SCSQ) were evaluated in 313 adolescents with MDD., Results: MDD adolescents with NSSI had higher CTQ-SF total score, emotional and sexual abuse subscale scores, but lower CDI total and subscale scores compared to the patients without NSSI. The multiple linear regression analysis revealed that emotional abuse (β = 0.075, 95 % CI: 0.042-0.107) and ineffectiveness (β = -0.084, 95 % CI: -0.160 ∼ -0.009) were significantly associated with the frequency of NSSI in adolescents with MDD, but emotional abuse (β = 0.884, 95 % CI: 0.570-1.197), sexual abuse (β = 0.825, 95 % CI: 0.527-1.124) and negative coping style (β = 0.370, 95 % CI: 0.036-0.704) were independently associated with the depressive severity in these adolescents. Furthermore, the mediation analysis demonstrated that positive coping style partially mediates the effect of childhood trauma on NSSI (Indirect effect = 0.002, 95 % bootCI: 0.001-0.004), while the negative coping style partially mediates the relationship between childhood trauma and depressive severity (Indirect effect = 0.024, 95 % bootCI: 0.005-0.051) in adolescents with MDD., Limitations: A cross-sectional design, the retrospective self-reported data, the small sample size., Conclusion: Our findings suggest that coping styles may serve as mediators on the path from childhood trauma to NSSI or depressive severity in MDD adolescents., Competing Interests: Declaration of competing interest This study was performed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: The Sang Yu granule (SY), a traditional Chinese medicine prescription of Xijing Hospital, was developed based on the Guanyin powder in the classical prescription "Hong's Collection of Proven Prescriptions" and the new theory of modern Chinese medicine. It has been proved to have a certain therapeutic effect on drug-induced liver injury (DILI), but the specific mechanism of action is still unclear., Aim of Study: Aim of the study was to explore the effect of SangYu granule on treating drug-induced liver injury induced by acetaminophen in mice., Materials and Methods: The chemical composition of SY, serum, and liver tissue was analyzed using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry. To assess hepatic function, measurements were taken using kits for total bile acids, as well as serum AST, ALT, and ALP activity. Concentrations of IL-1β and TNF-α in serum were quantified using ELISA kits. Transcriptome Sequencing Analysis and 2bRAD-M microbial diversity analysis were employed to evaluate gene expression variance in liver tissue and fecal microbiota diversity among different groups, respectively. Western blotting was performed to observe differences in the activation levels of FXR, SHP, CYP7A1 and PPARα in the liver, and the levels of FXR and FGF-15 genes and proteins in the ileum of mice. Additionally, fecal microbiota transplantation (FMT) experiments were conducted to investigate the potential therapeutic effect of administering the intestinal microbial suspension from mice treated with SY on drug-induced liver injury., Results: SY treatment exhibited significant hepatoprotective effects in mice, effectively ameliorating drug-induced liver injury while concurrently restoring intestinal microbial dysbiosis. Furthermore, SY administration demonstrated a reduction in the concentration of total bile acids, the expression of FXR and SHP proteins in the liver was up-regulated, CYP7A1 protein was down-regulated, and the expressions of FXR and FGF-15 proteins in the ileum were up-regulated. However, no notable impact on PPARα was observed. Furthermore, results from FMT experiments indicated that the administration of fecal suspensions derived from mice treated with SY did not yield any therapeutic benefits in the context of drug-induced liver injury., Conclusion: The aforementioned findings strongly suggest that SY exerts a pronounced ameliorative effect on drug-induced liver injury through its ability to modulate the expression of key proteins involved in bile acid secretion, thereby preserving hepato-enteric circulation homeostasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chiral allylic alcohols are highly prized in synthetic chemistry due to their versatile reactivity stemming from both alkenyl and hydroxyl functionalities. While the Nozaki-Hiyama-Kishi (NHK) reaction is a widely used method for the synthesis of allylic alcohols, it suffers from drawbacks such as the use of toxic chromium salts, high amounts of metal reductants, and poor enantiocontrol. To address these limitations, we present a novel approach involving a metallaphotoredox-catalyzed asymmetric NHK reaction for the production of chiral allylic alcohols. This method marries alkenyl (pseudo)halides with aldehydes, leveraging a synergistic blend of a chiral nickel catalyst and a photocatalyst. This innovative technique enables both oxidative addition and insertion just using nickel, diverging significantly from the conventional NHK reaction pathway mediated by nickel and chromium salts. The adoption of this methodology holds immense promise for crafting a spectrum of intricate compounds, particularly those of significance in pharmaceuticals. Detailed experimental investigations have shed light on the metallaphotoredox process, further enhancing our understanding and enabling further advancements., (© 2024 Wiley-VCH GmbH.)

PM 2.5 exposure has been found to cause gut dysbiosis and impair glucose homeostasis in human and animals, yet their underlying biological connection remain unclear. In the present study, we aim to investigate the biological significance of gut microbiota in PM 2.5 -induced glucose metabolic abnormalities. Our results showed that microbiota depletion by antibiotics treatment significantly alleviated PM 2.5 -induced glucose intolerance and insulin resistance, as indicated by the intraperitoneal glucose tolerance test, glucose-induced insulin secretion, insulin tolerance test, insulin-induced phosphorylation levels of Akt and GSK-3β in insulin sensitive tissues. In addition, faecal microbiota transplantation (FMT) from PM 2.5 -exposed donor mice successfully remodeled the glucose metabolism abnormalities in recipient mice, while the transplantation of autoclaved faecal materials did not. Faecal microbiota analysis demonstrated that the composition and alpha diversity of the gut bacterial community were altered by PM 2.5 exposure and in FMT recipient mice. Furthermore, short-chain fatty acids levels analysis showed that the circulating acetate was significantly decreased in PM 2.5 -exposed donor and FMT recipient mice, and supplementation of sodium acetate for 3 months successfully improved the glucose metabolism abnormalities induced by PM 2.5 exposure. These results indicate that manipulating gut microbiota or its metabolites could be a potential strategy for preventing the adverse health effects of ambient PM 2.5 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The kidney is the most commonly affected organ in sepsis patients, and Kruppel-like transcription factor 15 (KLF15) has a kidney-protective effect and is highly enriched in the kidneys. This study aims to explore the role of KLF15 in sepsis-related acute kidney injury., Methods: A septic injury model in HK2 cells was established through the administration of lipopolysaccharide (LPS), followed by the transfection of an overexpression plasmid for KLF15. Cell viability was assessed using CCK-8 assay, and apoptosis was measured via flow cytometry. The levels of inflammatory cytokines were detected using ELISA, and Western blot (WB) assay was employed to assess the expression of KLF15, PPARδ, as well as inflammatory and apoptosis-related proteins. The interaction between KLF15 and PPARδ was confirmed through the utilization of online databases and immunoprecipitation (IP) experiments. The mechanism was further validated using PPARδ agonists and small interfering RNA (siRNA)., Results: LPS-induced HK2 cells showed down-regulated expression of KLF15 and PPARδ, along with decreased viability, accompanied by increased levels of apoptosis, TNFα, IL-1β, and IL-6. Additionally, LPS upregulated the expression of Bax, cytoplasmic cytochrome C [Cytc (cyt)], Cox-2, and p-NF-κB-p65 in HK2 cells, while simultaneously downregulating the expression of Bcl2 and mitochondrial cytochrome c [Cytc (mit)]. IP experiment revealed a possible interaction between KLF15 and PPARδ in HK2 cells. Ov-KLF15, Ov-PPARδ or administration of PPARδ agonists effectively alleviated the aforementioned alterations induced by LPS. However, interference with PPARδ significantly attenuated the protective effect of Ov-KLF15 on HK2 cells., Conclusion: KLF15 attenuates LPS-induced apoptosis and inflammatory responses in HK2 cells via PPARδ., (Copyright © 2024 by the Shock Society.)

In orchestrating cell signaling, facilitating plasma membrane repair, supervising protein secretion, managing waste elimination, and regulating energy consumption, lysosomes are indispensable guardians that play a crucial role in preserving intracellular homeostasis. Neurons are terminally differentiated post-mitotic cells. Neuronal function and waste elimination depend on normal lysosomal function. Converging data suggest that lysosomal dysfunction is a critical event in the etiology of Parkinson's disease (PD). Mutations in Glucosylceramidase Beta 1 (GBA1) and leucine-rich repeat kinase 2 (LRRK2) confer an increased risk for the development of parkinsonism. Furthermore, lysosomal dysfunction has been observed in the affected neurons of sporadic PD (sPD) patients. Given that lysosomal hydrolases actively contribute to the breakdown of impaired organelles and misfolded proteins, any compromise in lysosomal integrity could incite abnormal accumulation of proteins, including α-synuclein, the major component of Lewy bodies in PD. Clinical observations have shown that lysosomal protein levels in cerebrospinal fluid may serve as potential biomarkers for PD diagnosis and as signs of lysosomal dysfunction. In this review, we summarize the current evidence regarding lysosomal dysfunction in PD and discuss the intimate relationship between lysosomal dysfunction and pathological α-synuclein. In addition, we discuss therapeutic strategies that target lysosomes to treat PD., (© 2024. The Author(s).)

Exosomes are increasingly being regarded as emerging and promising biomarkers for cancer screening, diagnosis, and therapy. The downstream molecular analyses of exosomes were greatly affected by the isolation efficiency from biosamples. Among the current exosome isolation strategies, affinity nanomaterials performed comparably better with selectivity and specificity. However, these techniques did not take the structure and size of exosomes into account, which may lead to a loss of isolation efficiency. In this article, a framework nucleic acid was employed to prepare a well-designed nanosized bead Fe 3 O 4 @pGMA@DNA TET@Ti 4+ for enrichment of exosomes. The abundant phosphate groups in the framework nucleic acid provide binding sites to immobilize Ti 4+ , and its rigid three-dimensional skeleton makes them act as roadblocks to barricade exosomes and provide affinity interactions on a three-dimensional scale, resulting in the improvement of isolation efficiency. The model exosomes can be effectively isolated with 92% recovery in 5 min. From 100 μL of HeLa cell culture supernatant, 34 proteins out of the top 100 commonly identified exosomal proteins were identified from the isolated exosomes by the novel beads, which is obviously more than that by TiO 2 (19 proteins), indicating higher isolation efficiency and exosome purity by Fe 3 O 4 @pGMA@DNA TET@Ti 4+ beads. The nanobeads were finally applied for comparing exosomal proteomics analysis from real clinical serum samples. Twenty-five upregulated and 10 downregulated proteins were identified in the lung cancer patients group compared to the health donors group, indicating that the novel nanobeads have great potential in isolation of exosomes for exosomal proteomics analysis in cancer screening and diagnosis.

Vascular dementia (VaD) is a prevalent form of dementia stemming from cerebrovascular disease, manifesting in memory impairment and executive dysfunction, thereby imposing a substantial societal burden. Unfortunately, no drugs have been approved for the treatment of VaD due to its intricate pathogenesis, and the development of innovative and efficacious medications is urgently needed. Apoptosis, a programmed cell death process crucial for eliminating damaged or unwanted cells within an organism, assumes pivotal roles in embryonic development and tissue homeostasis maintenance. An increasing body of evidence indicates that apoptosis may significantly influence the onset and progression of VaD, and numerous natural compounds have demonstrated significant therapeutic potential. Here, we discuss the molecular mechanisms underlying apoptosis and its correlation with VaD. We also provide a crucial reference for developing innovative pharmaceuticals by systematically reviewing the latest research progress concerning the neuroprotective effects of natural compounds on VaD by regulating apoptosis. Further high-quality clinical studies are imperative to firmly ascertain these natural compounds' clinical efficacy and safety profiles in the treatment of VaD., (© 2024 John Wiley & Sons Ltd.)

Roasted-rice leachate fermentation, a distinctive local tobacco fermentation method in Sichuan, imparts a mellow flavor and glossy texture to tobacco leaves, along with a roasted rice aroma. In order to find out the impact of roasted-rice leachate on cigar tobacco leaves, the physicochemical properties, volatile flavor profile, and microbial community were investigated. The content of protein significantly decreased after fermentation. The volatile flavor compounds increased following roasted-rice leachate fermentation, including aldehydes, alcohols, acids, and esters. High-throughput sequencing identified Staphylococcus, Pseudomonas, Pantoea, Oceanobacillus, Delftia, Corynebacterium, Sphingomonas, Aspergillus, Weissella, and Debaryomyces as the primary genera. Network and correlation analysis showed Debaryomyces played a crucial role in roasted-rice leachate fermentation, due to its numerous connections with other microbes and positive relationships with linoelaidic acid, aromandendrene, and benzaldehyde. This study is useful for gaining insight into the relationship between flavor compounds and microorganisms and provides references regarding the effect of extra nutrients on traditional fermentation products. KEY POINTS: • Volatile flavor compounds increased following roasted-rice leachate fermentation • Staphylococcus was the primary genera in fermented cigar • Debaryomyces may improve the quality of tobacco leaves., (© 2024. The Author(s).)

This study aimed to develop and evaluate a guinea pig model for glaucoma, comparing resultant eyeball enlargement with an existing myopia model. Thirty guinea pigs underwent intracameral injection of magnetic microspheres to induce chronic ocular hypertension (COH). Intraocular pressure (IOP) was systematically monitored, revealing a successful induction of COH in 73.33% of the guinea pigs. The mean IOP increased from a baseline of 18.04 ± 1.33 mmHg, reaching a peak at week 3 (36.31 ± 6.13 mmHg) and remaining elevated for at least 7 weeks. All data are presented as mean ± standard deviation of the mean. Subsequently, detailed assessments were conducted to validate the established glaucoma model. Immunofluorescent staining demonstrated a significant decrease in the density of retinal ganglion cells (RGC) in the glaucoma group. Optic disc excavation and notable thinning of the lamina cribrosa (LC) were observed. The quantity of optic nerve ax·ons in glaucoma group gradually decreased from baseline (44553 ± 3608/mm 2 ) to week 4 (28687 ± 2071/mm 2 ) and week 8 (17977 ± 3697/mm 2 ). Moreover, regarding the global enlargement of eyeballs, both the transverse and longitudinal axis in glaucomatous eyes were found to be significantly larger than that in myopic eyes, particularly in the anterior chamber depth (1.758 ± 0.113 mm vs. 1.151 ± 0.046 mm). These findings indicate distinct patterns of structural changes associated with glaucoma and myopia in the guinea pig model. This guinea pig model holds promise for future research aimed at exploring biomechanical mechanisms, therapeutic interventions, and advancing our understanding of the relationship between glaucoma and myopia., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Buyang Huanwu Decoction (BHD) is widely used in Chinese clinical practice for the treatment and prevention of ischemic cerebral vascular diseases. This study was designed to investigate the effects of BHD on ischemic stroke (IS) and its underlying mechanism., Methods: The middle cerebral artery occlusion (MCAO) rat model and oxygen-glucose deprivation and reoxygenation (OGD/R) rat brain microvascular endothelial cell (RBMVEC) models were established. Brain infarction size and neurological score were calculated following MCAO surgery. Evans blue was used to measure blood brain barrier (BBB) permeability. Cell counting kit-8 (CCK-8) and TUNEL assays were performed to evaluate the cell viability and apoptosis of RBMVECs. Dual-luciferase reporter assay was used to analyze the transcriptional activities of apoptosis-related genes., Results: Results showed that higher infarction volume, neurological scores, and BBB permeability in the MCAO group rats were reduced after BHD treatment. Drug serum (DS) treatment had no impact on the normal RBMVECs' cell viability and cell apoptosis. Besides, DS treatment decreased the lactate production, glucose uptake, and extracellular acidification rate in normal and OGD/R-induced RBMVECs. DS treatment downregulated the protein levels of pan-lysine lactylation (kla), histone H3 lysine 18 lactylation (H3K18la), and the transcriptional of apoptotic protease activating factor-1 (Apaf-1) in OGD/R-treated RBMVECs. In addition, Apaf-1 overexpression decreased cell viability and increased apoptosis and glycolysis activity of OGD/R-treated RBMVECs., Conclusion: In summary, BHD inhibited glycolysis and apoptosis via suppressing the pan-kla and H3K18la protein levels and the Apaf-1 transcriptional activity, thus restraining the progression of IS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Schizophrenia is a severe psychiatric disorder, characterized by positive symptoms, negative symptoms, and cognitive deficits. Elucidating the mechanism of negative symptom and cognitive deficits could contribute to the treatment and prognosis of schizophrenia. We hypothesized that abnormal functional connectivity would be involved in the indirect effects of negative symptoms on cognitive function., Methods: A total of 150 schizophrenia male patients and 108 healthy controls matched for age, education and gender were enrolled in the study. The scores of Brief Negative Symptom Scale were divided into two factors: motivation and pleasure deficits (MAP) and diminished expression (EXP). Subsequently, a series of classic neurocognitive tests were used to evaluate cognitive functions. Resting-state fMRI data was collected from all participants. The Anatomical Automatic Labeling template was employed to establish regions of interest, thereby constructing the functional connectivity network across the entire brain. Eventually, scores of patients' negative symptoms scale, cognitive function, and strengths of abnormal functional connectivity were incorporated into a structural equation model to explore the interactions among variables., Results: MAP exhibited a distinctly and significantly negative impact on cognitive function. The functional connectivity between the left insula and left precuneus, along with that between the left precuneus and right angular gyrus, collectively served as intermediaries, contributing to the indirect effects of MAP and EXP on cognitive function., Conclusions: Our findings demonstrated the moderating role of aberrant brain functional connectivity between negative symptoms and cognitive function, providing clues about the neural correlates of negative symptoms and cognitive deficits in schizophrenia., Competing Interests: Declaration of competing interest None to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Disorders of gut-brain interaction (DGBI) are characterized by debilitating symptoms not explained by structural or biochemical abnormalities. While functional conditions present with complex, likely heterogeneous pathophysiology, we aimed to investigate if proxy measures of sociocultural and environmental factors are associated with the prevalence of various DGBI in populations across the world., Methods: We performed an ecological study utilizing peer-reviewed published datasets reporting for 26 countries prevalence rates of DGBI (Rome Foundation Global Epidemiology Study, RFGES), with six independent variables: Helicobacter pylori prevalence and household size as proxy measures for orofecal infections, gross domestic product per capita (GDP), and median age as a proxy measures for socioeconomic development, density of fast food outlets (FFO) per 100,000 population as proxy measure for processed food exposure, and suicide mortality rate per 100,000 people, and world happiness scores were used as a proxy for psychological stress. The data were retrieved from publicly accessible datasets (United Nations, CIA World Factbook, World Bank, World Happiness Report, commercial/financial reports of a global FFO chain). We used linear regression to assess variables in univariate and multivariate analysis and report standardized β coefficients with 95% confidence intervals (CI)., Key Results: The regression model revealed that the overall prevalence of DGBI was inversely associated with both GDP per capita (β = -0.57, 95% CI: -0.92, -0.22, p = 0.002) and happiness scores (β = -0.433 95% CI: 0.821, -0.065, p = 0.023), while being positively associated with H. pylori prevalence (β = 0.40, 95% CI: 0.008, 0.81, p = 0.046). The prevalence of functional constipation (FC) was also inversely associated with GDP per capita (β = -0.50, 95% CI: -0.86, -0.13, p = 0.01) and happiness scores (β = -0.497, 95% CI: -0.863, -0.132, p = 0.01), while being positively associated with H. pylori prevalence (β = 0.53, 95% CI: 0.16, 0.91, p = 0.007). The Multivariate model analysis revealed that combining the factors of H. pylori prevalence, suicide rate, household size and happiness scores showed statistically significant association with FC (p = 0.039). Household size (β = -0.43, 95% CI: -0.82, 0.038, p = 0.033) and suicide rates (β = 0.55, 95% CI: 0.19, 0.90, p = 0.004) were statistically significantly associated with functional diarrhea. Irritable bowel syndrome (IBS) was associated with GDP per capita (β = -0.40, 95% CI: -0.79, -0.014, p = 0.043) and happiness scores (β = -0.390, 95% CI: -0.778, -0.003, p = 0.049)., Conclusions & Inferences: Utilizing publicly available data, the prevalence of DGBI across diverse countries is linked to various socio-cultural and environmental factors. Collectively, the data suggests that the prevalence of DGBI is increased in less prosperous regions of the world., (© 2024 The Author(s). Neurogastroenterology & Motility published by John Wiley & Sons Ltd.)

In the pathogenesis of osteoarthritis, various signaling pathways may influence the bone joint through a common terminal pathway, thereby contributing to the pathological remodeling of the joint. Semaphorins (SEMAs) are cell-surface proteins actively involved in and primarily responsible for regulating chondrocyte function in the pathophysiological process of osteoarthritis (OA). The significance of the SEMA family in OA is increasingly acknowledged as pivotal. This review aims to summarize the mechanisms through which different members of the SEMA family impact various structures within joints. The findings indicate that SEMA3A and SEMA4D are particularly relevant to OA, as they participate in cartilage injury, subchondral bone remodeling, or synovitis. Additionally, other elements such as SEMA4A and SEMA5A may also contribute to the onset and progression of OA by affecting different components of the bone and joint. The mentioned mechanisms demonstrate the indispensable role of SEMA family members in OA, although the detailed mechanisms still require further exploration., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Exosomes, as membranous vesicles generated by multiple cell types and secreted to extracellular space, play a crucial role in a range of brain injury-related brain disorders by transporting diverse proteins, RNA, DNA fragments, and other functional substances. The nervous system's pathogenic mechanisms are complicated, involving pathological processes like as inflammation, apoptosis, oxidative stress, and autophagy, all of which result in blood-brain barrier damage, cognitive impairment, and even loss of normal motor function. Exosomes have been linked to the incidence and progression of brain disorders in recent research. As a result, a thorough knowledge of the interaction between exosomes and brain diseases may lead to the development of more effective therapeutic techniques that may be implemented in the clinic. The potential role of exosomes in brain diseases and the crosstalk between exosomes and other pathogenic processes were discussed in this paper. Simultaneously, we noted the delicate events in which exosomes as a media allow the brain to communicate with other tissues and organs in physiology and disease, and compiled a list of natural compounds that modulate exosomes, in order to further improve our understanding of exosomes and propose new ideas for treating brain disorders., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

JOURNAL/nrgr/04.03/01300535-202409000-00042/figure1/v/2024-01-16T170235Z/r/image-tiff Parkinson's disease is a neurodegenerative disease characterized by motor and gastrointestinal dysfunction. Gastrointestinal dysfunction can precede the onset of motor symptoms by several years. Gut microbiota dysbiosis is involved in the pathogenesis of Parkinson's disease, whether it plays a causal role in motor dysfunction, and the mechanism underlying this potential effect, remain unknown. CCAAT/enhancer binding protein β/asparagine endopeptidase (C/EBPβ/AEP) signaling, activated by bacterial endotoxin, can promote α-synuclein transcription, thereby contributing to Parkinson's disease pathology. In this study, we aimed to investigate the role of the gut microbiota in C/EBPβ/AEP signaling, α-synuclein-related pathology, and motor symptoms using a rotenone-induced mouse model of Parkinson's disease combined with antibiotic-induced microbiome depletion and fecal microbiota transplantation. We found that rotenone administration resulted in gut microbiota dysbiosis and perturbation of the intestinal barrier, as well as activation of the C/EBP/AEP pathway, α-synuclein aggregation, and tyrosine hydroxylase-positive neuron loss in the substantia nigra in mice with motor deficits. However, treatment with rotenone did not have any of these adverse effects in mice whose gut microbiota was depleted by pretreatment with antibiotics. Importantly, we found that transplanting gut microbiota derived from mice treated with rotenone induced motor deficits, intestinal inflammation, and endotoxemia. Transplantation of fecal microbiota from healthy control mice alleviated rotenone-induced motor deficits, intestinal inflammation, endotoxemia, and intestinal barrier impairment. These results highlight the vital role that gut microbiota dysbiosis plays in inducing motor deficits, C/EBPβ/AEP signaling activation, and α-synuclein-related pathology in a rotenone-induced mouse model of Parkinson's disease. Additionally, our findings suggest that supplementing with healthy microbiota may be a safe and effective treatment that could help ameliorate the progression of motor deficits in patients with Parkinson's disease., (Copyright © 2024 Copyright: © 2024 Neural Regeneration Research.)

Pickering emulsions provide a promising platform for the efficient delivery of bioactive. However, co-delivery of fragile bioactives with different physicochemical properties for comprehensive effects still faces practical challenges due to the limited protection for bioactives and the lack of stimuli-responsive property for on-demand release. Herein, a stimuli-responsive co-delivery system is developed based on biomineralized particles stabilized Pickering emulsions. In this tailor co-delivery system, hydrophilic bioactive (pepsin) with the fragile structure is encapsulated and immobilized by biomineralization, the obtained biomineralized particles (PPS@CaCO 3 ) are further utilized as emulsifiers to form O/W Pickering emulsions, in which the hydrophobic oxidizable bioactive (curcumin) is stably trapped into the dispersed phase. The results show that two bioactives are successfully co-encapsulated in Pickering emulsions, and benefiting from the protection capacities of biomineralization and Pickering emulsions, the activity of pepsin and curcumin shows a 7.33-fold and 144.83-fold enhancement compared to the free state, respectively. Moreover, In vitro study demonstrates that Pickering emulsions enable to co-release of two bioactives with high activity retention by the acid-induced hydrolyzation of biomineralized particles. This work provides a powerful stimuli-responsive platform for the co-delivery of multiple bioactive compounds, enabling high activity of bioactives for the comprehensive health effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Inappropriate perioperative fluid load can lead to postoperative complications and death. This retrospective study was designed to investigate the association between intraoperative fluid load and outcomes in neonates undergoing non-cardiac surgery. From April 2020 to September 2022, 940 neonates who underwent non-cardiac surgery were retrospectively enrolled and their perioperative data were harvested for further analysis. According to recorded intraoperative fluid volumes defined as ml.kg -1 h -1 , patients were mandatorily divided into quintile with fluid load as restrictive (quintile 1, Q1), moderately restrictive (Q2), moderate (Q3), moderately liberal (Q4), and liberal (Q5). The primary outcomes were defined as prolonged length of hospital stay (LOS) (postoperative LOS ≥ 14 days), complications beyond prolonged LOS, and 30-day mortality. Secondary outcomes included postoperative complications within 14 days of hospital stay. The intraoperative fluid load was in Q1 of 6.5 (5.3-7.3) (median and IQR); Q2: 9.2 (8.7-9.9); Q3: 12.2 (11.4-13.2); Q4: 16.5 (15.4-18.0); and Q5: 26.5 (22.3-32.2) ml.kg -1 h -1 . The odd of prolonged LOS was positively correlated with an increase fluid volume (Q5 quintile: OR 2.602 [95% CI 1.444-4.690], P = 0.001), as well as complications beyond prolonged LOS (Q5: OR 3.322 [95% CI 1.656-6.275], P = 0.001). The overall 30-day mortality rate was increased with high intraoperative fluid load but did not reach to a statistical significance after adjusted with confounders. Furthermore, the highest quintile of fluid load (26.5 ml.kg -1 h -1 , IQR [22.3-32.2]) (Q5 quintile) was significantly associated with longer postoperative mechanical ventilation time compared with Q1 (Q5: OR 2.212 [95% CI 1.101-4.445], P = 0.026).    Conclusion: Restrictive intraoperative fluid load had overall better outcomes, whilst high fluid load was significantly associated with prolonged LOS and complications after non-cardiac surgery in neonates.    Trial registration:  Chictr.org.cn Identifier: ChiCTR2200066823 (December 19, 2022). What is Known: • Inappropriate perioperative fluid load can lead to postoperative complications and even death. What is New: • High perioperative fluid load was significantly associated with an increased length of stay after non-cardiac surgery in neonates, whilst low fluid load was consistently related to better postoperative outcomes., (© 2024. The Author(s).)

Endometrial carcinoma is one of most common malignant tumors in women, and ferroptosis is closely related to the development and treatment of endometrial carcinoma. The aim of this study was to screen ferroptosis-related genes associated with endometrial carcinoma and predict targeted drugs through bioinformatics. 761 differentially expressed genes were obtained by the dataset GSE63678 from the GEO database, and most of the genes were enriched in the KEGG_CELL_CYCLE and KEGG_OOCYTE_MEIOSIS signaling pathways. 22 ferroptosis-differentially expressed genes were obtained by intersection with the FerrDb database. These genes were involved in biological processes including macromolecular complex assembly and others, and involved in signal pathways including glutathione metabolism, p53 signaling pathway and others. CDKN2A, IDH1, NRAS, TFRC and GOT1 were obtained as hub genes by PPI network analysis. GEPIA showed that CDKN2A, IDH1, NRAS and TFRC were significantly expressed in endometrial carcinoma. Immunohistochemical results showed that CDKN2A, NRAS and TFRC were significantly expressed in endometrial carcinoma clinical tissue samples. The ROC constructed by TCGA database showed that CDKN2A, NRAS and TFRC had significant value in the diagnosis of endometrial carcinoma, and all had prognostic efficacy. 136,572-09-3 BOSS and others were identified as potential targeted drugs for endometrial carcinoma targeting ferroptosis. Our study has shown that ferroptosis-related genes CDKN2A, NRAS and TFRC are diagnostic markers of endometrial carcinoma, and 136,572-09-3 BOSS, methyprylon BOSS, daunorubicin CTD 00005752, nitroglycerin BOSS and dUTP BOSS, IRON BOSS, Imatinib mesylate BOSS, 2-Butanone BOSS, water BOSS, and L-thyroxine BOSS may be potential therapeutic drugs., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background Aims: Mesenchymal stromal cells (MSCs) are attractive as a therapeutic modality in multiple disease conditions characterized by inflammation and vascular compromise. Logistically they are advantageous because they can be isolated from adult tissue sources, such as bone marrow (BM). The phase 2a START clinical trial determined BM-MSCs to be safe in patients with moderate-to-severe acute respiratory distress syndrome (ARDS). Herein, we examine a subset of the clinical doses of MSCs generated for the phase 2a START trial from three unique donors (1-3), where one of the donors' donated BM on two separate occasions (donor 3 and 3W)., Methods: The main objective of this study was to correlate properties of the cells from the four lots with plasma biomarkers from treated patients and relevant to ARDS outcomes. To do this we evaluated MSC donor lots for (i) post-thaw viability, (ii) growth kinetics, (iii) metabolism, (iv) surface marker expression, (v) protein expression, (vi) immunomodulatory ability and (vii) their functional effects on regulating endothelial cell permeability., Results: MSC-specific marker expression and protection of thrombin-challenged endothelial barrier permeability was similar among all four donor lots. Inter and intra-donor variability was observed in all the other in vitro assays. Furthermore, patient plasma ANG-2 and protein C levels at 6 hours post-transfusion were correlated to cell viability in an inter- and intra-donor dependent manner., Conclusions: These findings highlight the potential of donor dependent (inter-) and collection dependent (intra-) effects in patient biomarker expression., Competing Interests: Declaration of Competing Interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: This study aims to develop a deep learning framework for the automatic detection of the position relationship between the mandibular third molar (M3) and the mandibular canal (MC) on panoramic radiographs (PRs), to assist doctors in assessing and planning appropriate surgical interventions., Methods: Datasets D1 and D2 were obtained by collecting 253 PRs from a hospitals and 197 PRs from online platforms. The RPIFormer model proposed in this study was trained and validated on D1 to create a segmentation model. The CycleGAN model was trained and validated on both D1 and D2 to develop an image enhancement model. Ultimately, the segmentation and enhancement models were integrated with an object detection model to create a fully automated framework for M3 and MC detection in PRs. Experimental evaluation included calculating Dice coefficient, IoU, Recall, and Precision during the process., Results: The RPIFormer model proposed in this study achieved an average Dice coefficient of 92.56 % for segmenting M3 and MC, representing a 3.06 % improvement over the previous best study. The deep learning framework developed in this research enables automatic detection of M3 and MC in PRs without manual cropping, demonstrating superior detection accuracy and generalization capability., Conclusion: The framework developed in this study can be applied to PRs captured in different hospitals without the need for model fine-tuning. This feature is significant for aiding doctors in accurately assessing the spatial relationship between M3 and MC, thereby determining the optimal treatment plan to ensure patients' oral health and surgical safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Problematic internet use (PIU) and depression usually co-occur and are common among college students. According to network theory, it may be attributed to the interplay of symptoms that connect these two mental health problems. However, most studies have failed to examine complex and subtle connections at the symptom level and have not clarified how PIU and depression symptoms are intercorrelated, which symptoms serve as the source of comorbidity (i.e., the central symptoms), and whether such a comorbidity mechanism would change with higher grades. To explore these questions, this study examined four contemporaneous networks and three cross-lagged panel networks, visualizing the symptoms as nodes and the connections between symptoms as edges. A total of 2,420 college students (M age  = 18.35, SD = 0.84; 67.98 % girls) completed four annual surveys. Overall, the results of contemporaneous networks and cross-lagged panel networks indicated that (a) PIU and depression symptoms are intercorrelated; (b) the core symptoms responsible for comorbidity mostly belonged to PIU, and (c) the comorbidity mechanism would change with time. These findings explain the dynamic relation between PIU and depression and identify possible primary symptoms that comorbidity programs can mitigate at different stages of the college years., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Camouflaged objects often blend in with their surroundings, making the perception of a camouflaged object a more complex procedure. However, most neural-network-based methods that simulate the visual information processing pathway of creatures only roughly define the general process, which deficiently reproduces the process of identifying camouflaged objects. How to make modeled neural networks perceive camouflaged objects as effectively as creatures is a significant topic that deserves further consideration. After meticulous analysis of biological visual information processing, we propose an end-to-end prudent and comprehensive neural network, termed IdeNet, to model the critical information processing. Specifically, IdeNet divides the entire perception process into five stages: information collection, information augmentation, information filtering, information localization, and information correction and object identification. In addition, we design tailored visual information processing mechanisms for each stage, including the information augmentation module (IAM), the information filtering module (IFM), the information localization module (ILM), and the information correction module (ICM), to model the critical visual information processing and establish the inextricable association of biological behavior and visual information processing. The extensive experiments show that IdeNet outperforms state-of-the-art methods in all benchmarks, demonstrating the effectiveness of the five-stage partitioning of visual information processing pathway and the tailored visual information processing mechanisms for camouflaged object detection. Our code is publicly available at: https://github.com/whyandbecause/IdeNet.

China ranks 160 out of 180 countries in terms of ecological efficiency, with an EPI score of 28.40 and a 10-year average change in score of 11.40. This article examines the impact of green finance and China's natural resources on regional ecological efficiency using the Tobit regression model. The study uses the average yearly exchange rate to normalize dollar-related values and GDP to 2012 RMB using the price deflator. Variables used as explanatory tools include green financing, the availability of natural resources, and regional eco-efficiency. The results of the study imply that natural resources in eastern region of China are better managed as and have avoided the resource curse as compared to central and western regions. Resources temporarily support area economic and social growth. However, resource agglomeration locks many elements in the resource industry and degrades regional industrial development, generating environmental and social difficulties that may hinder regional economic progress. Given that Foreign Direct Investment (FDI) increases regional eco-efficiency after accounting for adjustment. The FDI positively correlated with ecological efficiency in the east zone, while central and western zones have negative correlations. The industrial development of the nation negatively impacts ecological efficiency in the East, Midwest, and West regions. Western results are distinctive, with ecological efficiency and regional economic growth frequently going hand in hand., (© 2024. The Author(s).)

The success of polymerase chain reaction (PCR) depends on the quality of deoxyribonucleic acid (DNA) templates. This study developed a cost-effective and eco-friendly DNA extraction system utilizing poly(3,4-dihydroxyphenylalanine)-modified cellulose paper (polyDOPA@paper). PolyDOPA@paper was prepared by oxidatively self-polymerizing DOPA under weak alkaline conditions and utilizing the adhesive property of polyDOPA on different materials. Compared to the uncoated cellulose paper, polyDOPA coating significantly enhances DNA adsorption owing to its abundant amino, carboxyl, and hydroxyl moieties. The DNA extraction mechanism using polyDOPA@paper was discussed. The maximum adsorption capacity of polyDOPA@paper for DNA was 20.7 μg cm -2 . Moreover, an automated extraction system was designed and fabricated using 3D printing technology. The device simplifies the operation and ensures the reproducibility and consistency of the results. More importantly, it eliminates the need for specialized training of operators. The feasibility of the polyDOPA@paper-based automated extraction system was evaluated by quantitatively detecting Escherichia coli in spiked milk samples via a real-time PCR. The detection limit was 10 2 cfu mL -1 . The results suggest that the system would have significant potential in detecting pathogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Camellia saponins are important by-products of Camellia Oleifer Abel. processing. In this study, an eco-friendly method based on natural deep eutectic solvents (NaDESs, proline and glycerol at a molar ratio of 2:5) was established to extract saponins from C.oleifera cakes. The content of saponin (702.22 ± 1.28 mg/g) obtained using NaDES was higher than those extracted using water or methanol. UPLC-Q-TOF MS analysis of chemical structure showed that the difference in the extraction technique alter individual saponins. A widely targeted metabolomic approach and KEGG metabolic pathway analysis showed that the upregulated metabolites in the NaDES-based extract mainly included flavonoids, alkaloids, and phenolic acids; and they were involved in arginine and proline metabolism, metabolic pathways, phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, and flavonoid biosynthesis. The present study proposes a selective substitute for use in the extraction of camellia saponins with composition analysis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Individuals are apt to link various characteristics of an object or event through different sensory experiences. We conducted two electrophysiological experiments to investigate the effects of color-flavor congruency and association strength on visual search efficiency and the in-depth cognitive mechanisms underlying multisensory processes. Participants were prompted with a flavor label and asked to identify the primed flavor from four beverage bottle images. Experiment 1 focused on color-flavor congruency and noted faster searches for congruent targets than incongruent ones. EEG data exhibited smaller N2, larger P3 and LPC, and increased parietal-occipital midline (POM) alpha power for incongruent targets than congruent ones. Experiment 2 manipulated color-flavor association strength within each flavor. Behavioral findings showed that searches for targets with weak association strength took longer than those with strong association strength. Moreover, time-frequency analysis displayed that the former evoked greater frontal midline (FM) theta power and higher alpha power than the latter. Altogether, our research indicated that (1) color expectations based on prior experience can automatically guide people's attentional selection, (2) the color-flavor congruency and association strength impact the visual search efficiency via distinct pathways, and (3) theta and alpha activities make a pivotal role in unraveling multisensory information processing. These findings shed some light on the intricate cognitive processes involved in crossmodal visual search and the underlying neurocognitive dynamics., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Globally, women 15-24 years are at heightened risk of sexual violence victimization, a risk factor for adverse mental, physical, and behavioral health outcomes. Sexual violence is common at universities and most often perpetrated by men, yet few evidence-based prevention strategies targeting men have been tested in low- and middle-income countries. GlobalConsent is a six-module, web-based educational program adapted from an efficacious U.S.-based program. Nine months post-treatment in a randomized trial in Vietnam, GlobalConsent reduced men's sexually violent behavior (odds ratio [OR] = 0.71, 95%CI 0.50-1.00) and increased prosocial intervening behavior (OR = 1.51, 1.00-2.28) relative to an attention-control. Evidence regarding optimal implementation strategies for scale up is needed., Methods: We will randomize six medical universities in North, Central, and South Vietnam to deliver GlobalConsent using two different packages of implementation strategies that vary in intensity. Higher-intensity strategies will include greater (1) pre- and post-implementation engagement with university leaders and faculty and (2) greater pre-implementation outreach, follow-up, and incentives for students to promote engagement and completion of GlobalConsent. Higher intensity universities will receive additional training and support for their added activities. We will compare implementation drivers and outcomes, intervention effectiveness, and cost-effectiveness across the two implementation bundles. Our mixed-methods comparative interrupted time series design includes (1) qualitative interviews and quantitative surveys with university leaders and implementation teams to assess implementation barriers and facilitators; (2) repeated surveys with leaders and faculty, implementation teams, and male students to assess multilevel implementation drivers and outcomes; (3) repeated surveys with male students to assess behavioral outcomes (sexual violence and intervening behavior) and mediating variables (knowledge, attitudes, affect, and capacities); and (4) time diaries and cost tracking to assess cost-effectiveness of the two implementation-strategies bundles., Discussion: This project is the first to assess packages of implementation strategies to deliver an efficacious web-based sexual violence prevention program for undergraduate men across all regions of Vietnam and synergizes with a violence-prevention training initiative (D43TW012188). This approach will produce rigorous evidence about how to disseminate GlobalConsent nationally, which holds promise to reduce gender-based health inequities linked to sexual violence as GlobalConsent is brought to scale., Trial Registration: NCT06443541. Retrospectively registered with ClinicalTrials.gov. Registered on June 05, 2024., (© 2024. The Author(s).)

Equol is a highly active product of soy isoflavones produced by specific bacteria in the human or animal colon. However, equol production is influenced by differences in the gut flora carried by the body. Our previous research has shown that a synbiotic preparation comprising the probiotic Lactobacillus rhamnosus ATCC 7469 and the prebiotic lactulose can enhance equol production by modulating the intestinal flora. Nevertheless, the harsh environment of the gastrointestinal tract limits this capability by diminishing the number of probiotics reaching the colon. Microencapsulation of probiotics is an effective strategy to enhance their viability. In this study, probiotic gel microspheres (SA-S-CS) were prepared using an extrusion method, with sodium alginate (SA) and chitosan (CS) serving as the encapsulating materials. Scanning electron microscopy (SEM) was employed to observe the surface morphology and the internal distribution of bacteria within the microcapsules. The structural characteristics of the microcapsules were investigated using Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Furthermore, the thermal stability, storage stability, probiotic viability post-simulated gastrointestinal fluid treatment, and colon release rate were examined. Finally, the impact of probiotic microencapsulation on promoting equol production by the synbiotic preparation was assessed. The results indicated that the microcapsules exhibited a spherical structure with bacteria evenly distributed on the inner surface. Studies on thermal and storage stability showed that the number of viable cells in the probiotic microcapsule group significantly increased compared to the free probiotic group. Gastrointestinal tolerance studies revealed that after in vitro simulated gastrointestinal digestion, the amount of viable cells in the microcapsules was 7 log 10 CFU g -1 , demonstrating good gastrointestinal tolerance. Moreover, after incubation in simulated colonic fluid for 150 min, the release rate of probiotics reached 93.13%. This suggests that chitosan-coated sodium alginate microcapsules can shield Lactobacillus rhamnosus ATCC 7469 from the gastrointestinal environment, offering a novel model for synbiotic preparation to enhance equol production.

Aim: Transcriptional regulation of gene expression plays a crucial role in orchestrating complex morphogenetic and molecular events during heart development and function. Mediator complex is an essential multi-subunit protein complex that governs gene expression in eukaryotic cells. Although Mediator subunits (MEDs) work integrally in the complex, individual MED component displays specialized functions. MED27, categorized as an Upper Tail subunit, possesses an as-yet-uncharacterized function. In this study, we aimed to investigate the physiological role of MED27 in cardiomyocytes., Materials and Methods: we generated a Med27 floxed mouse line, which was further used to generate constitutive (cKO) and inducible (icKO) cardiomyocyte-specific Med27 knockout mouse models. Morphological, histological analysis and cardiac physiological studies were performed in Med27 cKO and icKO mutants. Transcriptional profiles were determined by RNA sequencing (RNAseq) analysis., Key Fundings: Ablation of MED27 in developing mouse cardiomyocytes results in embryonic lethality, while its deletion in adult cardiomyocytes leads to heart failure and mortality. Similar to the ablation of another Upper Tail subunit, MED30 in cardiomyocytes, deletion of MED27 leads to decreased protein levels of most MEDs in cardiomyocytes. Interestingly, overexpression of MED30 fails to restore the protein levels of Mediator subunits in MED27-deficient cardiomyocytes, demonstrating that the role of MED27 in maintaining the integrity and stability of the Mediator complex is independent of MED30., Significance: Our results revealed an essential role of MED27 in cardiac development and function by maintaining the stability of the Mediator core., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Rhinosinusitis and intracranial hemorrhage are prevalent conditions within their respective medical specialties. While rhinosinusitis is predominantly an inflammatory disease confined to the paranasal sinuses, it can, in exceedingly rare circumstances, lead to intracranial hemorrhage with potentially fatal outcomes. Despite the gravity of this rare association, the literature remains sparse regarding its pathophysiological mechanisms, natural history, management principles, and clinical outcomes., Methods: We present a systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and a case illustration of epitural hematoma arising from rhinosinusitis., Results: A systematic review of the literature identified 20 published cases of intracranial hemorrhage induced by rhinosinusitis, plus the case presented herein, the total number of cases is 21. Nineteen epidural hematomas (EDH) and 2 subdural hematomas(SDH) were identified. The frontal region (14/19, 74%) was the most prevalent location for EDH corresponding to sinusitis related to the frontal sinus (12/14, 86%). Common symptoms included headache (n=18, 86%), fever and impaired consciousness (n=13, 62%), and periorbital swelling/pain (n=8, 38%). Interventions included hematoma removal/drainage, rhinosinus surgery, and antibiotic therapies. One fatality and three residual neurological impairments occurred. Multiple hypotheses exist regarding the mechanisms of intracranial hemorrhage in rhinosinusitis., Conclusions: Intracranial hemorrhagic complications, primarily EDH and SDH, are rare and potentially fatal consequences of rhinosinusitis. It should be cognizant of the potential existence of such a possibility during clinical practice., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Intervertebral disc degeneration (IVDD) is a common spine disease with inflammation as its main pathogenesis. Mulberroside A (MA), isolated from herbal medicine, possesses anti-inflammatory characteristics in many diseases. Whereas, there is little exploration of the therapeutic potential of MA on IVDD. This study aimed at the therapeutic potential of MA on IVDD in vivo and in vitro and the mechanism involved., Methods: In vitro, western blotting, RT-qPCR, and immunofluorescence analysis were implemented to explore the bioactivity of MA on interleukin-1 beta (IL-1β)-induced inflammation nucleus pulposus cells (NPCs) isolated from Sprague-Dawley male rats. In vivo, X-ray and MRI were applied to measure the morphological changes, and histological staining and immunohistochemistry were employed to investigate the histological changes of intervertebral disc sections on puncture-induced IVDD rat models., Results: In vitro, MA up-regulated the expression level of anabolic-related proteins (Aggrecan and Collagen II) and decreased catabolic-related proteins (Mmp2, Mmp3, Mmp9, and Mmp13) in IL-1β-induced NPCs. Furthermore, MA inhibits the production of pro-inflammatory factors (Inos, Cox-2, and Il-6) stimulated by IL-1β. Mechanistically, MA inhibited the signal transduction of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) pathways in IL-1β-induced NPCs. Moreover, MA might bind to Ppar-γ and then suppress the NF-kB pathway. In vivo experiment illustrated that MA mitigates the IVDD progression in puncture-induced IVDD model. X-ray and MRI images showed MA restore the disc height and T2-weighted signal intensity after puncturing. H&E and Safranin O/Fast Green also showed MA also alleviated morphological changes caused by acupuncture. In addition, MA reversed the expression level of Mmp13, Aggrecan, Collagen II, and Ppar-γ induced in IVDD models., Conclusions: MA inhibited degenerative phenotypes in NPCs and alleviated IVDD progression via inhibiting the MAPK and NF-κB pathways; besides, MA suppressed the NF-κB pathway was attributed to activating Ppar-γ, those supported that MA or Ppar-γ might be a potential drug or target for IVDD., (© 2024. The Author(s).)

Single-ion conductive polymer electrolytes can improve the safety of lithium ion batteries (LIBs) by increasing the lithium transference number ( t Li + ) and avoiding the growth of lithium dendrites. Meanwhile, the self-assembled ordered structure of liquid crystal polymer networks (LCNs) can provide specific channels for the ordered transport of Li ions. Herein, single-ion conductive nematic and cholesteric LCN electrolyte membranes (denoted as NLCN-Li and CLCN-Li) were successfully prepared. NLCN-Li was then coated on commercial Celgard 2325 while CLCN-Li was coated on poly(vinylidene fluoride-hexafluoropropylene) film, coupled with plasticizer, to make NLCN-Li/Cel and CLCN-Li/Pv quasi-solid-state electrolyte membranes, respectively. Their electrochemical properties were evaluated, and it was found that they possessed benign thermal stability and electrolyte/electrode compatibility, high t Li + up to 0.98 and high electrochemical stability window up to 5.2 V. A small amount (0.5M) of extra Li salt added to the plasticizer could improve the ion conductivity from 1.79 × 10 -5 to 5.04 × 10 -4 S cm -1 , while the t Li + remained 0.85. The assembled LFP|Li batteries also exhibited excellent cycling and rate performances. The orderliness of the LCN layer played an important role in the distribution and movement of Li ions, thereby affecting the Li deposition and growth of Li dendrites. As the first report of nematic and cholesteric LCN single-ion conductors, this work sheds light on the design and fabrication of ordered quasi-solid-state electrolytes for high-performance and safe LIBs.

Cetuximab in combination with FOLFIRI/FOLFOX is the standard first-line treatment for patients with RAS wild-type metastatic colorectal cancer (mCRC). However, some patients experience rapid tumor progression after treatment with cetuximab (primary resistance). Our previous research identified a gene mutation, REV1 p.R704Q, which may be a key biomarker for primary cetuximab resistance. This study aimed to study the mechanism of cetuximab resistance caused by REV1 p.R704Q mutation and reveal a novel mechanism to induce cetuximab resistance. Sanger sequencing and multivariate clinical prognostic analysis of 208 patients with mCRC showed that REV1 p.R704Q mutation is an independent risk factor for tumor progression after treatment with cetuximab in patients with RAS wild-type mCRC (Hazard ratio = 2.481, 95 % Confidence interval: 1.389-4.431, P = 0.002). The sensitivity of REV1 p.R704Q mutant cell lines to cetuximab decreased in vitro Cell Counting Kit-8 assay and in vivo subcutaneous tumor model. In vitro, we observed that decreased stability and accelerated degradation of REV1 mutant protein results in REV1 dysfunction, which activated autophagy and mediated cetuximab resistance. These findings suggested that REV1 p.R704Q mutation could predict cetuximab primary resistance in mCRC. REV1 p.R704Q mutation caused decreased stability and degradation of REV1 protein, as well as dysfunction of p.R704Q protein. REV1 p.R704Q mutation activates autophagy and mediates cetuximab resistance; further, inhibition of autophagy could reverse cetuximab resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

With the application of low frequency radar and the demand for stealth of high temperature resistant components, it is increasingly urgent to develop absorbing materials with both low frequency and high temperature resistant properties. Here, we successfully prepared various carbon/polyimide composites as low-frequency electromagnetic wave absorbing materials by simple blending method. The well-designed mesh lap structure introduces a large amount of free space, further optimizing the impedance matching of the material. At the same time, the multiple loss mechanism formed by the combination of carbon black dominated polarization and carbon nanotube dominated conductive loss enhances the loss of incident electromagnetic wave. The results showed that only 10 wt% filler loading of the CB/CNT@PI is achieved in the low frequency range (1-4 GHz) with a minimum RL strength of - 18.3 dB, which has obvious advantages compared with other works in recent years. This study provides a way for the design and preparation of resin-based absorbing materials., (© 2024 IOP Publishing Ltd. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)

The performance of BACT/ALERT FA/FN Plus (France) blood culture containing a novel resin, DL (China) blood culture containing common resin, and adsorbent-free REDOX (USA) blood culture relying on dilution for antimicrobial neutralization at %peak serum concentration was evaluated by measuring the recovery of organisms and time to detection (TTD) in nine simulated microorganism-antimicrobial combination blood cultures. Significant differences were observed in the recovery rates among the aerobic media: 87.5% for BACT/ALERT media, 42.9% for DL media, and 12.5% for REDOX media. In contrast, no statistical difference was found in the TTD between FA Plus media and DL aerobic media. For the anaerobic media, the recovery rates were 91.4% for BACT/ALERT media, 2.9% for DL media, and 14.3% for REDOX media, with significant differences only between BACT/ALERT FN Plus media and the others. Among the seven main antimicrobial categories, only BACT/ALERT FA/FN Plus culture media demonstrated high recovery of microorganisms, with the exception of carbapenems. The DL culture media exhibited a relatively high recovery rate of microorganisms in the presence of piperacillin/tazobactam, levofloxacin, and gentamicin, but only in aerobic conditions. Conversely, REDOX media displayed microorganism recovery solely in the presence of gentamicin. BACT/ALERT FA/FN Plus culture media with novel resin showed absolute advantages over DL and REDOX culture media and can, therefore, be selectively applied in clinical settings when antimicrobials are used prior to blood collection. DL culture media, containing common resin, outperformed adsorbent-free dilution-based REDOX culture media, making it a viable backup option. There is a need to focus on improving the neutralization of carbapenems with current inefficiency in all three medias., Importance: We present a study on performance comparison of three different commercial culture media for neutralization of antibiotic effects in simulated blood cultures. BACT/ALERT (FA Plus and FN Plus) culture media with novel resin showed absolute advantages over DL and REDOX culture media at %PSL concentration of antimicrobials.

Vitrification of oocyte has become an important component of assisted reproductive technology and has important implications for animal reproduction and the preservation of biodiversity. However, vitrification adversely affects mitochondrial function and oocyte developmental potential, mainly because of oxidative damage. Rutin is a highly effective antioxidant, but no information is available to the effect of rutin on the mitochondrial function and development in vitrified oocytes. Therefore, we studied the effects of rutin supplementation of vitrification solution on mitochondrial function and developmental competence of ovine germinal vesicle (GV) stage oocytes post vitrification. The results showed that supplementation of vitrification solution with 0.6 mM rutin significantly increased the cleavage rate (71.6 % vs. 59.3 %) and blastocyst rate (18.9 % vs. 6.8 %) compared to GV-stage oocytes in the vitrified group. Then, we analyzed the reactive oxygen species (ROS), glutathione (GSH), mitochondrial activity and membrane potential (ΔΨm), endoplasmic reticulum (ER) Ca 2+ , and annexin V (AV) of vitrified sheep GV-stage oocytes. Vitrified sheep oocytes exhibited increased levels of ROS and Ca 2+ , higher rate of AV-positive oocytes, and decreased mitochondrial activity, GSH and ΔΨm levels. However, rutin supplementation in vitrification solution decreased the levels of ROS, Ca 2+ and AV-positive oocytes rate, and increased the GSH and ΔΨm levels in vitrified oocytes. Results revealed that rutin restored mitochondrial function, regulated Ca 2+ homeostasis and decreased apoptosis potentially caused by mitophagy in oocytes. To understand the mechanism of rutin functions in vitrified GV-stage oocytes in sheep, we analyzed the transcriptome and found that rutin mediated oocytes development and mitochondrial function, mainly by affecting oxidative phosphorylation and the mitophagy pathways. In conclusion, supplementing with 0.6 mM rutin in vitrification solution significantly enhanced developmental potential through improving mitochondrial function and decreased apoptosis potentially caused by mitophagy after vitrification of ovine GV-stage oocytes., Competing Interests: Declaration of competing interest The authors declare that they have no interest conflict., (Copyright © 2024 Elsevier Inc. All rights reserved.)