Milk fat globule membrane proteins are crucial in regulating lipid digestion during simulated in vitro infant gastrointestinal digestion.

Products of lipolysis released during digestion positively affect the metabolism of newborns. In contrast to the 3-layer biological membranes covering human milk (HM) fat, the lipid droplets in infant milk formula (IMF) are covered by a single membrane composed of casein and whey proteins. To reduce the differences in lipid structure between IMF and HM, studies have used milk fat globule membrane (MFGM) components such as milk polar lipids (MPL) to prepare emulsions mimicking HM fat globules However, few studies have elucidated the effect of membrane proteins (MP) on lipid digestion in infants. In this study, 3 kinds of emulsions were prepared: One with MPL as the interfaced of lipid droplets (RE-1), one with membrane protein concentrate (MPC) (RE-2) as the interface of lipid droplets, and one with both MPL and MPC (1:2) as the co-interface of lipid droplets (RE-3). The interfacial coverage of the emulsions was confirmed by measuring the contents of MPL and MPC at the lipid droplet interface, and by confocal laser scanning microscopy analyzed. By controlling the homogenization intensity, the specific surface area of lipid droplets was controlled at the same level among the 3 emulsions. The stability constants of the emulsions varied, and RE-1 was the most stable. During simulated in vitro infant gastrointestinal digestion, the amount of free fatty acids (FFA) released from the lipid droplets was significantly higher from those with MPC at the interface (RE-2, RE-3) than from that with MPL at the interface (RE-1). The amount of FFA released at the end of intestinal digestion of RE-1, RE-2, and RE-3 was 255.00 ± 3.54 µmol,328.75 ± 5.30 µmol, 298.50 ± 9.19 µmol, respectively. Compared with the lipid droplets in RE-2, those with MPL at the interface (RE-1, RE-3) released more unsaturated fatty acids (USFAs) during digestion. The emulsifying activity index was highest in RE-3 (MPL and MPC co-interface). The presence of MPL at the emulsion interface increased the release of USFAs, while the presence of MPC increased the release of FFA. These results show that both MPL and MP are indispensable in the construction of MFGM. Understanding their effects on digestion can provide new strategies for the development of infant foods.

The role of Atg5 gene in tumorigenesis under autophagy deficiency conditions.

Autophagy is a self-recycling machinery to maintain cellular homeostasis by degrading harmful materials in the cell. Autophagy-related gene 5 (Atg5) is required for autophagosome maturation. However, the role of Atg5 in tumorigenesis under autophagy deficient conditions remains unclear. This study focused on the autophagy-independent role of Atg5 and the underlying mechanism in tumorigenesis. We demonstrated that knockout of autophagy-related genes including Atg5, Atg7, Atg9, and p62 in mouse embryonic fibroblast (MEF) cells consistently decreased cell proliferation and motility, implying that autophagy is required to maintain diverse cellular functions. An Atg7 knockout MEF (Atg7-/- MEF) cell line representing deprivation of autophagy function was used to clarify the role of Atg5 transgene in tumorigenesis. We found that Atg5-overexpressed Atg7-/-MEF (clone A) showed increased cell proliferation, colony formation, and migration under autophagy deficient conditions. Accordingly, rescuing the autophagy deficiency of clone A by overexpression of Atg7 gene shifts the role of Atg5 from pro-tumor to anti-tumor status, indicating the dual role of Atg5 in tumorigenesis. Notably, the xenograft mouse model showed that clone A of Atg5-overexpressed Atg7-/- MEF cells induced temporal tumor formation, but could not prolong further tumor growth. Finally, biomechanical analysis disclosed increased Wnt5a secretion and p-JNK expression along with decreased ß-catenin expression. In summary, Atg5 functions as a tumor suppressor to protect the cell under normal conditions. In contrast, Atg5 shifts to a pro-tumor status under autophagy deprivation conditions.

Efficacy of real-time artificial intelligence-aid endoscopic ultrasonography diagnostic system in discriminating gastrointestinal stromal tumors and leiomyomas: a multicenter diagnostic study.

Background: Gastrointestinal stromal tumors (GISTs) represent the most prevalent type of subepithelial lesions (SELs) with malignant potential. Current imaging tools struggle to differentiate GISTs from leiomyomas. This study aimed to create and assess a real-time artificial intelligence (AI) system using endoscopic ultrasonography (EUS) images to differentiate between GISTs and leiomyomas. Methods: The AI system underwent development and evaluation using EUS images from 5 endoscopic centers in China between January 2020 and August 2023. EUS images of 1101 participants with SELs were retrospectively collected for AI system development. A cohort of 241 participants with SELs was recruited for external AI system evaluation. Another cohort of 59 participants with SELs was prospectively enrolled to assess the real-time clinical application of the AI system. The AI system's performance was compared to that of endoscopists. This study is registered with Chictr.org.cn, Number ChiCT2000035787. Findings: The AI system displayed an area under the curve (AUC) of 0.948 (95% CI: 0.921-0.969) for discriminating GISTs and leiomyomas. The AI system's accuracy (ACC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) reached 91.7% (95% CI 87.5%-94.6%), 90.3% (95% CI 83.4%-94.5%), 93.0% (95% CI 87.2%-96.3%), 91.9% (95% CI 85.3%-95.7%), and 91.5% (95% CI 85.5%-95.2%), respectively. Moreover, the AI system exhibited excellent performance in diagnosing ≤20 mm SELs (ACC 93.5%, 95% CI 0.900-0.969). In a prospective real-time clinical application trial, the AI system achieved an AUC of 0.865 (95% CI 0.764-0.966) and 0.864 (95% CI 0.762-0.966) for GISTs and leiomyomas diagnosis, respectively, markedly surpassing endoscopists [AUC 0.698 (95% CI 0.562-0.834) for GISTs and AUC 0.695 (95% CI 0.546-0.825) for leiomyomas]. Interpretation: We successfully developed a real-time AI-assisted EUS diagnostic system. The incorporation of the real-time AI system during EUS examinations can assist endoscopists in rapidly and accurately differentiating various types of SELs in clinical practice, facilitating improved diagnostic and therapeutic decision-making. Funding: Science and Technology Commission Foundation of Shanghai Municipality, Science and Technology Commission Foundation of the Xuhui District, the Interdisciplinary Program of Shanghai Jiao Tong University and the Research Funds of Shanghai Sixth people's Hospital.

Dual-mRNA Delivery Using Tumor Cell Lysate-Based Multifunctional Nanoparticles as an Efficient Colon Cancer Immunogene Therapy.

Background: Messenger RNA (mRNA)-based immunogene therapy holds significant promise as an emerging tumor therapy approach. However, the delivery efficiency of existing mRNA methods and their effectiveness in stimulating anti-tumor immune responses require further enhancement. Tumor cell lysates containing tumor-specific antigens and biomarkers can trigger a stronger immune response to tumors. In addition, strategies involving multiple gene therapies offer potential optimization paths for tumor gene treatments. Methods: Based on the previously developed ideal mRNA delivery system called DOTAP-mPEG-PCL (DMP), which was formed through the self-assembly of 1.2-dioleoyl-3-trimethylammonium-propane (DOTAP) and methoxypoly (ethylene glycol)-b-poly (ε-caprolactone) (mPEG-PCL), we introduced a fused cell-penetrating peptide (fCPP) into the framework and encapsulated tumor cell lysates to form a novel nanovector, termed CLSV system (CLS: CT26 tumor cell lysate, V: nanovector). This system served a dual purpose of facilitating the delivery of two mRNAs and enhancing tumor immunogene therapy through tumor cell lysates. Results: The synthesized CLSV system had an average size of 241.17 nm and a potential of 39.53 mV. The CLSV system could not only encapsulate tumor cell lysates, but also deliver two mRNAs to tumor cells simultaneously, with a transfection efficiency of up to 60%. The CLSV system effectively activated the immune system such as dendritic cells to mature and activate, leading to an anti-tumor immune response. By loading Bim-encoded mRNA and IL-23A-encoded mRNA, CLSV/Bim and CLSV/IL-23A complexes were formed, respectively, to further induce apoptosis and anti-tumor immunity. The prepared CLSV/dual-mRNA complex showed significant anti-cancer effects in multiple CT26 mouse models. Conclusion: Our results suggest that the prepared CLSV system is an ideal delivery system for dual-mRNA immunogene therapy.

Complete Laparoscopic Type C2 Radical Surgery for Cervical Stump Cancer: No-Look and No-Touch Techniques.

BACKGROUND: Due to previous surgical history and subsequent adhesions between pelvic organs, surgery for cervical stump cancer (CSC) is technically more challenging than surgery for cervical cancer with an intact uterus.1 We aimed to illustrate the related anatomy, surgical steps and techniques of complete laparoscopic type C2 radical surgery (CLRS) for early-stage CSC. METHODS: CLRS for six patients with CSC was performed from January 2021 to January 2022. We demonstrated the detailed skills of parametrial management during CLRS for CSC in case 5 by means of a video. A 58-year-old woman diagnosed with International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIA1 CSC received CLRS through five operative ports (Fig. 1). RESULTS: The magnetic resonance imaging (MRI) scans and gross appearance of the specimen are shown in Fig. 2. The median age and body mass index (BMI) of the six patients were 53 years and 23.8, respectively. The median blood loss was 275 mL; the median time of operation was 218 min; the median length of hospitalization was 15 days; and the median time to recover urinary function was 12 days. One patient underwent postoperative radiation for pathologically proven adenocarcinoma with deep stromal invasion,2 while the other five did not. After a median follow-up of 24 months, no patients experienced complications, recurrence, or death (Table 1). CONCLUSIONS: This study details the skills of CLRS for CSC, especially space development and the 'no-look, no-touch' tumor-free principle. It is helpful for clinicians to perform safe and standardized surgery on patients with early-stage CSC. Fig. 1 Trocar placement of complete laparoscopic type C2 radical surgery for early-stage CSC. CSC cervical stump cancer, S superior, I inferior, R right, L left, U umbilicus Fig. 2 MRI scans and gross appearance of the specimen for case 5 with CSC at FIGO 2018 stage IIA1. The tumor lesion on the cervical stump is indicated by yellow arrows. a Axial T2-weighted image; b DKI image; c ADC map; d sagittal T2-weighted image; e sagittal T1-weighted image; f gross appearance of the surgical specimen. MRI magnetic resonance imaging, CSC cervical stump cancer, FIGO International Federation of Gynecology and Obstetrics, DKI diffusional kurtosis imaging, ADC apparent diffusion coefficient Table 1 Clinicopathological characteristics, operative details, and outcomes of patients with cervical stump cancer Patient no. Age at diagnosis (years) BMI Reasons for subtotal hysterectomy FIGO 2018 stage Histology Operation Operation time (mins) Blood loss (mL) Urinary catheter (days) Hospital stay (days) Complications Depth of invasion LVSI LNs dissected TNM stage Tumor size (mm) Postoperative radiotherapy Follow-up (months) Recurrence Death 1 50 25.9 Uterine myoma IIA1 ASC CLRS+PLND 221 360 10 12 No Middle one-third N 13 T2a1N0M0 16 No 30 No No 2 55 17.3 Uterine myoma IB1 AC CLRS+PLND 191 270 20 12 No Deep one-third N 24 T1b1N0M0 10 Yes 20 No No 3 50 24.8 Uterine myoma IB1 SC CLRS+PLND 295 310 13 15 No Superficial one-third N 21 T1b1N0M0 15 No 25 No No 4 63 30.1 Uterine myoma IB1 SC CLRS+PLND 213 180 6 16 No Superficial one-third N 25 T1b1N0M0 15 No 19 No No 5 58 20.2 Postpartum hemorrhage IIA1 SC CLRS+PLND 220 100 11 14 No Middle one-third N 21 T2a1N0M0 15 No 24 No No 6 46 22.7 Uterine myoma IB1 SC CLRS+PLND 215 120 14 17 No Superficial one-third N 26 T1b1N0M0 12 No 23 No No BMI body mass index, FIGO International Federation of Gynecology and Obstetrics, ASC cervical adenosquamous carcinoma, AC cervical adenocarcinoma, SC cervical squamous carcinoma, CLRS+PLND complete laparoscopic radical surgery and pelvic node dissections, LVSI lymphovascular space invasion, N negative, LNs lymph nodes, TNM tumor node metastasis.

Depression and the risk of dementia and all-cause mortality among Japanese older adults: A 9-year longitudinal study from JAGES.

BACKGROUND: This study aims to investigate the association and dose-response relationship between depression, dementia, and all-cause mortality based on a national cohort study of elderly people in Japan. METHODS: We conducted a longitudinal study of 44,546 participants aged ≥65 from 2010-2019 Japanese Gerontological Evaluation Study (JAGES). The Geriatric Depression Scale (GDS-15) was used to assess depressive symptoms and the long-term care insurance (LTCI) was used to assess dementia. Fine-gray models and Cox proportional hazard models were used to explore the effect of depression severity on the incidence of dementia and all-cause mortality, respectively. Causal mediation analysis (CMA) to explore the extent of association between dementia-mediated depression and all-cause mortality. RESULTS: We found that both minor and major depressive symptoms were associated with the increased cumulative incidence of dementia and all-cause mortality, especially major depressive symptoms (P < 0.001). The multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for dementia were 1.25 (1.19-1.32) for minor depressive symptoms and 1.42 (1.30-1.54) for major depressive symptoms in comparison to non-depression; P for trend < 0.001. The multivariable-adjusted HRs and 95% CIs for all-cause mortality were 1.27 (1.21-1.33) for minor depressive symptoms and 1.51 (1.41-1.62) for major depressive symptoms in comparison to non-depression; P for trend < 0.001. Depression has a stronger impact on dementia and all-cause mortality among the younger group. In addition, dementia significantly mediated the association between depression and all-cause mortality. DISCUSSION: Interventions targeting major depression may be an effective strategy for preventing dementia and premature death.

The association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio with type 2 diabetes mellitus: recent findings from NHANES 2007-2018.

OBJECTIVE: This study aims to assess the relationship between NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio) and Type 2 diabetes mellitus (T2DM) in US adults, using National Health and Nutrition Examination Survey (NHANES) data from 2007 to 2018. METHODS: This study explored the connection between NHHR and T2DM by analyzing a sample reflecting the adult population of the United States (n = 10,420; NHANES 2007-2018). NHHR was characterized as the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol. T2DM was defined based on clinical guidelines. This research used multivariable logistic models to examine the connection between NHHR and T2DM. Additionally, it included subgroup and interaction analyses to assess variations among different groups. Generalized additive models, smooth curve fitting, and threshold effect analysis were also employed to analyze the data further. RESULTS: The study included 10,420 subjects, with 2160 diagnosed with T2DM and 8260 without. The weighted multivariate logistic regression model indicated an 8% higher probability of T2DM for each unit increase in NHHR (OR: 1.08, 95% CI: 1.01-1.15) after accounting for all covariates. Subgroup analysis outcomes were uniform across various categories, demonstrating a significant positive relationship between NHHR and T2DM. Interaction tests showed that the positive link between NHHR and T2DM remained consistent regardless of age, body mass index, smoking status, moderate recreational activities, hypertension, or stroke history, with all interaction P-values exceeding 0.05. However, participants' sex appeared to affect the magnitude of the connection between NHHR and T2DM (interaction P-value < 0.05). Also, a nonlinear association between NHHR and T2DM was discovered, featuring an inflection point at 1.50. CONCLUSIONS: Our study suggests that an increase in NHHR may be correlated with a heightened likelihood of developing T2DM. Consequently, NHHR could potentially serve as a marker for estimating the probability of T2DM development.

Transcutaneous auricular vagal nerve stimulation for consciousness recovery in patients with prolonged disorders of consciousness (TAVREC): study protocol for a multicenter, triple-blind, randomized controlled trial in China.

INTRODUCTION: Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC). METHODS AND ANALYSIS: The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 µs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events. ETHICS AND DISSEMINATION: This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300073950.

COI1 F-box proteins regulate DELLA protein levels, growth, and photosynthetic efficiency in maize.

The F-box protein Coronatine Insensitive (COI) is a receptor for the jasmonic acid signaling pathway in plants. To investigate the functions of the six maize (Zea mays) COI proteins (COI1a, COI1b, COI1c, COI1d, COI2a, and COI2b), we generated single, double, and quadruple loss-of-function mutants. The pollen of the coi2a coi2b double mutant was inviable. The coi1 quadruple mutant (coi1-4x) exhibited shorter internodes, decreased photosynthesis, leaf discoloration, microelement deficiencies, and accumulation of DWARF8 and/or DWARF9, two DELLA family proteins that repress the gibberellic acid signaling pathway. Co-expression of COI and DELLA in Nicotiana benthamiana showed that the COI proteins trigger proteasome-dependent DELLA degradation. Many genes that are downregulated in the coi1-4x mutant are gibberellic acid-inducible. In addition, most of the proteins encoded by the downregulated genes are predicted to be bundle sheath- or mesophyll-enriched, including those encoding C4-specific photosynthetic enzymes. Heterologous expression of maize Coi genes in N. benthamiana showed that COI2a is nucleus-localized and interacts with maize jasmonate ZIM (zinc-finger inflorescence meristem) domain (JAZ) proteins, the canonical COI repressor partners. However, maize COI1a and COI1c showed only partial nuclear localization and reduced binding efficiency to the tested JAZ proteins. Together, these results show the divergent functions of the six COI proteins in regulating maize growth and defense pathways.

Intelligent cholinergic white matter pathways algorithm based on U-net reflects cognitive impairment in patients with silent cerebrovascular disease.

BACKGROUND AND OBJECTIVE: The injury of the cholinergic white matter pathway underlies cognition decline in patients with silent cerebrovascular disease (SCD) with white matter hyperintensities (WMH) of vascular origin. However, the evaluation of the cholinergic white matter pathway is complex with poor consistency. We established an intelligent algorithm to evaluate WMH in the cholinergic pathway. METHODS: Patients with SCD with WMH of vascular origin were enrolled. The Cholinergic Pathways Hyperintensities Scale (CHIPS) was used to measure cholinergic white matter pathway impairment. The intelligent algorithm used a deep learning model based on convolutional neural networks to achieve WMH segmentation and CHIPS scoring. The diagnostic value of the intelligent algorithm for moderate-to-severe cholinergic pathway injury was calculated. The correlation between the WMH in the cholinergic pathway and cognitive function was analysed. RESULTS: A number of 464 patients with SCD were enrolled in internal training and test set. The algorithm was validated using data from an external cohort comprising 100 patients with SCD. The sensitivity, specificity and area under the curve of the intelligent algorithm to assess moderate and severe cholinergic white matter pathway injury were 91.7%, 87.3%, 0.903 (95% CI 0.861 to 0.952) and 86.5%, 81.3%, 0.868 (95% CI 0.819 to 0.921) for the internal test set and external validation set. for the. The general cognitive function, execution function and attention showed significant differences among the three groups of different CHIPS score (all p<0.05). DISCUSSION: We have established the first intelligent algorithm to evaluate the cholinergic white matter pathway with good accuracy compared with the gold standard. It helps more easily assess the cognitive function in patients with SCD.

Trends in prevalence of hearing loss in adults in the USA 1999-2018: a cross-sectional study.

BACKGROUND: A better understanding of how the prevalence of hearing loss and its associated factors change over time could help in developing an appropriate program to prevent the development of hearing loss. METHODS: Population-representative cross-sectional data from the United States National Health and Nutrition Examination Survey (NHANES) were used to estimate the trends in the prevalence of hearing loss among adults in the USA over the period 1999-2018. A total of 15,498 adult participants aged 20 years or older had complete audiometric examination data. Logistic regression was employed to evaluate the trend in hearing loss; weighted Rao-Scott χ2 tests and univariate logistic regression analyses were used to examine the association between hearing loss and relevant factors. RESULTS: The overall hearing loss prevalence in 1999-2018 was 19.1% 19.1 (95% CI, 18.0-20.2%). The prevalence of hearing loss decreased in cycles (P for trend < 0.001). For participants aged 20-69 years, the prevalence decreased from 15.6% (95% CI, 12.9-18.4%) in 1999-2000 to 14.9% (95% CI, 13.2- 16.6%) in 2015-2016; for participants aged > 70 years the prevalence decreased from 79.9% (95% CI, 76.1-83.8%) in 2005-2006 to 64.5% (95% CI, 58.8-70.2%) in 2017-2018. Participants with hearing loss were likely to be older, male, non-Hispanic white, and to have not completed high school. Mild hearing loss was more prevalent among those aged 20-79 years; in those aged over 80 years the prevalence of moderate hearing loss exceeded that of mild loss. Among all otologically normal participants, hearing thresholds increased with age across the entire frequency range. CONCLUSIONS: The prevalence of hearing loss in USA adults changed over the period 1999-2018. The trends observed provide valuable insight for making public health plans and allocating resources to hearing care. Further investigation is necessary to monitor hearing loss and its potential risk factors.

Polygonatum kingianum Polysaccharides Enhance the Preventive Efficacy of Heat-Inactivated Limosilactobacillus reuteri WX-94 against High-Fat-High-Sucrose-Induced Liver Injury and Gut Dysbacteriosis.

Limosilactobacillus reuteri (L. reuteri) is an efficacious probiotic that could reduce inflammation and prevent metabolic disorders. Here, we innovatively found that Polygonatum kingianum polysaccharides (PKP) promoted proliferation and increased stability of L. reuteri WX-94 (a probiotic strain showing anti-inflammation potentials) in simulated digestive fluids in vitro. PKP was composed of galactose, glucose, mannose, and arabinose. The cell-free supernatant extracted from L. reuteri cultured with PKP increased ABTS•+, DPPH•, and FRAP scavenging capacities compared with the supernatant of the medium without PKP and increased metabolites with health-promoting activities, e.g., 3-phenyllactic acid, indole-3-lactic acid, indole-3-carbinol, and propionic acid. Moreover, PKP enhanced alleviating effects of heat-inactivated L. reuteri on high-fat-high-sucrose-induced liver injury in rats via reducing inflammation and regulating expressions of protein and genes involved in fatty acid metabolism (such as HIF1-α, FAßO, CPT1, and AMPK) and fatty acid profiles in liver. Such benefits correlated with its prominent effects on enriching Lactobacillus and short-chain fatty acids while reducing Dubosiella, Fusicatenilacter, Helicobacter, and Oscillospira. Our work provides novel insights into the probiotic property of PKP and emphasizes the great potential of the inactivated L. reuteri cultured with PKP in contracting unhealthy diet-induced liver dysfunctions and gut dysbacteriosis.

Analysis of the mediating effect between ehealth literacy and health self-management of undergraduate nursing students' mental health literacy.

BACKGROUND: Good health self-management positively affects the health of healthcare providers and their ability to manage their patients' health. This study explored the relationship between ehealth literacy, health self-management skills, and mental health literacy among undergraduate nursing students. Some studies have confirmed the correlation between e-health literacy and health self-management skills, while mental health literacy may be correlated with both, and this study aims to explore the relationship between the three. METHODS: A descriptive cross-sectional survey was conducted at a medical university in northwestern China among 385 Chinese undergraduate nursing students. Participants completed the General Information Questionnaire, the Adult Health Self-Management Skills Rating Scale, the Mental Health Literacy Rating Scale, and the eHealth Literacy Scale, and provided valid responses. The IBM SPSS 27.0 statistical software was used for data entry and descriptive analysis, t-test, ANOVA, and Pearson correlation analysis. The IBM Amos 26.0 was used to construct the mediation effect model, and the Bootstrap method was employed to test mediating effects. RESULTS: Mental health literacy, ehealth literacy, and health self-management skills of undergraduate nursing students were at a moderate to high level. Mental health literacy, ehealth literacy, and health self-management were positively correlated. Mental health literacy, particularly, played a partial mediating role of 31.1% ( 95% CI [0.307-1.418] ) between ehealth literacy and health self-management. CONCLUSIONS: Undergraduate nursing students' mental health literacy partially mediates the link between eHealth literacy and health self-management skills. Schools should emphasize the development of nursing students' e-health literacy and mental health literacy in order to improve their health self-management skills, which will not only bring about a better health outcome for the students, but will also benefit the health of the social population.

Towards Lipid from Microalgae: Products, Biosynthesis, and Genetic Engineering.

Microalgae can convert carbon dioxide into organic matter through photosynthesis. Thus, they are considered as an environment-friendly and efficient cell chassis for biologically active metabolites. Microalgal lipids are a class of organic compounds that can be used as raw materials for food, feed, cosmetics, healthcare products, bioenergy, etc., with tremendous potential for commercialization. In this review, we summarized the commercial lipid products from eukaryotic microalgae, and updated the mechanisms of lipid synthesis in microalgae. Moreover, we reviewed the enhancement of lipids, triglycerides, polyunsaturated fatty acids, pigments, and terpenes in microalgae via environmental induction and/or metabolic engineering in the past five years. Collectively, we provided a comprehensive overview of the products, biosynthesis, induced strategies and genetic engineering in microalgal lipids. Meanwhile, the outlook has been presented for the development of microalgal lipids industries, emphasizing the significance of the accurate analysis of lipid bioactivity, as well as the high-throughput screening of microalgae with specific lipids.

Diagnostic accuracy of magnetically guided capsule endoscopy with a detachable string for detecting oesophagogastric varices in adults with cirrhosis: prospective multicentre study.

OBJECTIVE: To evaluate the diagnostic accuracy and safety of using magnetically guided capsule endoscopy with a detachable string (ds-MCE) for detecting and grading oesophagogastric varices in adults with cirrhosis. DESIGN: Prospective multicentre diagnostic accuracy study. SETTING: 14 medical centres in China. PARTICIPANTS: 607 adults (>18 years) with cirrhosis recruited between 7 January 2021 and 25 August 2022. Participants underwent ds-MCE (index test), followed by oesophagogastroduodenoscopy (OGD, reference test) within 48 hours. The participants were divided into development and validation cohorts in a ratio of 2:1. MAIN OUTCOME MEASURES: The primary outcomes were the sensitivity and specificity of ds-MCE in detecting oesophagogastric varices compared with OGD. Secondary outcomes included the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices and the diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices. RESULTS: ds-MCE and OGD examinations were completed in 582 (95.9%) of the 607 participants. Using OGD as the reference standard, ds-MCE had a sensitivity of 97.5% (95% confidence interval 95.5% to 98.7%) and specificity of 97.8% (94.4% to 99.1%) for detecting oesophagogastric varices (both P<0.001 compared with a prespecified 85% threshold). When using the optimal 18% threshold for luminal circumference of the oesophagus derived from the development cohort (n=393), the sensitivity and specificity of ds-MCE for detecting high risk oesophageal varices in the validation cohort (n=189) were 95.8% (89.7% to 98.4%) and 94.7% (88.2% to 97.7%), respectively. The diagnostic accuracy of ds-MCE for detecting high risk oesophagogastric varices, oesophageal varices, and gastric varices was 96.3% (92.6% to 98.2%), 96.9% (95.2% to 98.0%), and 96.7% (95.0% to 97.9%), respectively. Two serious adverse events occurred with OGD but none with ds-MCE. CONCLUSION: The findings of this study suggest that ds-MCE is a highly accurate and safe diagnostic tool for detecting and grading oesophagogastric varices and is a promising alternative to OGD for screening and surveillance of oesophagogastric varices in patients with cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT03748563.

Molecular Insights into Water-Chloride and Water-Water Interactions in the Supramolecular Architecture of Aconine Hydrochloride Dihydrate.

Despite the previous preparation of aconine hydrochloride monohydrate (AHM), accurate determination of the crystal's composition was hindered by severely disordered water molecules within the crystal. In this study, we successfully prepared a new dihydrate form of the aconine hydrochloride [C25H42NO9+Cl-·2(H2O), aconine hydrochloride dihydrate (AHD)] and accurately refined all water molecules within the AHD crystal. Our objective is to elucidate both water-chloride and water-water interactions in the AHD crystal. The crystal structure of AHD was determined at 136 K using X-ray diffraction and a multipolar atom model was constructed by transferring charge-density parameters to explore the topological features of key short contacts. By comparing the crystal structures of dihydrate and monohydrate forms, we have observed that both AHD and AHM exhibit identical aconine cations, except for variations in the number of water molecules present. In the AHD crystal, chloride anions and water molecules serve as pivotal connecting hubs to establish three-dimensional hydrogen bonding networks and one-dimensional hydrogen bonding chain; both water-chloride and water-water interactions assemble supramolecular architectures. The crystal packing of AHD exhibits a complete reversal in the stacking order compared to AHM, thereby emphasizing distinct disparities between them. Hirshfeld surface analysis reveals that H···Cl- and H···O contacts play a significant role in constructing the hydrogen bonding network and chain within these supramolecular architectures. Furthermore, topological analysis and electrostatic interaction energy confirm that both water-chloride and water-water interactions stabilize supramolecular architectures through electrostatic attraction facilitated by H···Cl- and H···O contacts. Importantly, these findings are strongly supported by the existing literature evidence. Consequently, navigating these water-chloride and water-water interactions is imperative for ensuring storage and safe processing of this pharmaceutical compound.

ETS translocation variant 5 (ETV5) promotes CD4+ T cell-mediated intestinal inflammation and fibrosis in inflammatory bowel diseases.

E26 transformation-specific translocation variant 5 (ETV5) has been implicated in the pathogenesis of inflammatory bowel diseases (IBD). However, the exact roles of ETV5 in regulating CD4+ T cell-mediated intestinal inflammation and fibrosis formation remain unclear. Here, we reveal that ETV5 overexpression induced interleukin (IL)-9 and its transcription factor IRF4 expression in IBD CD4+ T cells under T helper type 9 (Th9) cells-polarizing conditions. The silencing of IRF4 inhibited ETV5-induced IL-9 expression. CD4+ T cell-specific ETV5 deletion ameliorated intestinal inflammation and fibrosis in trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis and CD4+ T cell-transferred recombination-activating gene-1 knockout (Rag1-/-) colitis mice, characterized by less CD4+ T cell infiltration and lower fibroblast activation and collagen deposition in the colonic tissues. Furthermore, IL-9 treatment aggressive TNBS-induced intestinal fibrosis in CD4+ T cell-specific ETV5 deletion and wild-type control mice. In vitro, human intestinal fibroblasts cocultured with ETV5 overexpressed-Th9 cells expressed higher levels of collagen I and III, whereas an inclusion of anti-IL-9 antibody could reverse this effect. Ribonucleic acid sequencing analysis demonstrated that IL-9 upregulated TAF1 expression in human intestinal fibroblasts. Clinical data showed that number of α-smooth muscle actin+TAF1+ fibroblasts are higher in inflamed mucosa of patients with IBD. Importantly, TAF1 small interfering ribonucleic acid treatment suppressed IL-9-mediated profibrotic effect in vitro. These findings reveal that CD4+ T cell-derived ETV5 promotes intestinal inflammation and fibrosis through upregulating IL-9-mediated intestinal inflammatory and fibrotic response in IBD. Thus, the ETV5/IL-9 signal pathway in T cells might represent a novel therapeutic target for intestinal inflammation and fibrosis in IBD.

Genomic and pangenomic analyses provide insights into the population history and genomic diversification of bottle gourd.

Bottle gourd (Lagenaria siceraria (Mol.) Strandl.) is an economically important vegetable crop and one of the earliest domesticated crops. However, the population history and genomic diversification of bottle gourd have not been extensively studied. We generated a comprehensive bottle gourd genome variation map from genome sequences of 197 world-wide representative accessions, which enables a genome-wide association study for identifying genomic loci associated with resistance to zucchini yellow mosaic virus, and constructed a bottle gourd pangenome that harbors 1534 protein-coding genes absent in the reference genome. Demographic analyses uncover that domesticated bottle gourd originated in Southern Africa c. 12 000 yr ago, and subsequently radiated to the New World via the Atlantic drift and to Eurasia through the efforts of early farmers in the initial Holocene. The identified highly differentiated genomic regions among different bottle gourd populations harbor many genes contributing to their local adaptations such as those related to disease resistance and stress tolerance. Presence/absence variation analysis of genes in the pangenome reveals numerous genes including those involved in abiotic/biotic stress responses that have been under selection during the world-wide expansion of bottle gourds. The bottle gourd variation map and pangenome provide valuable resources for future functional studies and genomics-assisted breeding.

Prospective Investigation of Optical Genome Mapping for Prenatal Genetic Diagnosis.

BACKGROUND: Optical genome mapping (OGM) is a novel assay for detecting structural variants (SVs) and has been retrospectively evaluated for its performance. However, its prospective evaluation in prenatal diagnosis remains unreported. This study aimed to prospectively assess the technical concordance of OGM with standard of care (SOC) testing in prenatal diagnosis. METHODS: A prospective cohort of 204 pregnant women was enrolled in this study. Amniotic fluid samples from these women were subjected to OGM and SOC testing, which included chromosomal microarray analysis (CMA) and karyotyping (KT) in parallel. The diagnostic yield of OGM was evaluated, and the technical concordance between OGM and SOC testing was assessed. RESULTS: OGM successfully analyzed 204 cultured amniocyte samples, even with a cell count as low as 0.24 million. In total, 60 reportable SVs were identified through combined OGM and SOC testing, with 22 SVs detected by all 3 techniques. The diagnostic yield for OGM, CMA, and KT was 25% (51/204), 22.06% (45/204), and 18.14% (37/204), respectively. The highest diagnostic yield (29.41%, 60/204) was achieved when OGM and KT were used together. OGM demonstrated a concordance of 95.56% with CMA and 75.68% with KT in this cohort study. CONCLUSIONS: Our findings suggest that OGM can be effectively applied in prenatal diagnosis using cultured amniocytes and exhibits high concordance with SOC testing. The combined use of OGM and KT appears to yield the most promising diagnostic outcomes.