Forsythoside B, the active component of Frosythiae fructuse water extract, alleviates Streptococcus pneumoniae virulence by targeting pneumolysin.

AIMS: To explore the therapeutic potential of Forsythoside B in treating Streptococcus pneumoniae (S. pneumoniae) infections, focusing on its ability to inhibit pneumolysin activity and protect cells from damage. METHODS AND RESULTS: Hemolysis tests were used to evaluate Forsythoside B's inhibitory effect on pneumolysin activity, while growth curve analysis assessed its impact on S. pneumoniae growth. Western blotting and oligomerization analysis were conducted to examine its influence on pneumolysin oligomerization. Cytotoxicity assays, including LDH release and live/dead cell staining, evaluated the protective effects of Forsythoside B against pneumolysin-induced damage in A549 cells. Additionally, a mouse model was employed to test the effects on survival rates, lung bacterial load, and inflammation. The results showed that Forsythoside B significantly inhibited pneumolysin activity, reduced its oligomerization, and protected A549 cells from damage without affecting bacterial growth. In the mouse model, it improved survival rates and reduced lung inflammation, indicating its potential as a therapeutic agent against S. pneumoniae infections. CONCLUSIONS: Forsythoside B shows potential as a therapeutic agent for treating pneumonia, particularly in infections caused by S. pneumoniae.

Federated learning via multi-attention guided UNet for thyroid nodule segmentation of ultrasound images.

Accurate segmentation of thyroid nodules is essential for early screening and diagnosis, but it can be challenging due to the nodules' varying sizes and positions. To address this issue, we propose a multi-attention guided UNet (MAUNet) for thyroid nodule segmentation. We use a multi-scale cross attention (MSCA) module for initial image feature extraction. By integrating interactions between features at different scales, the impact of thyroid nodule shape and size on the segmentation results has been reduced. Additionally, we incorporate a dual attention (DA) module into the skip-connection step of the UNet network, which promotes information exchange and fusion between the encoder and decoder. To test the model's robustness and effectiveness, we conduct the extensive experiments on multi-center ultrasound images provided by 17 local hospitals. The model is trained using the federal learning mechanism to ensure privacy protection. The experimental results show that the Dice scores of the model on the data sets from the three centers are 0.908, 0.912 and 0.887, respectively. Compared to existing methods, our method demonstrates higher generalization ability on multi-center datasets and achieves better segmentation results.

Assessment of diagnostic value of unilateral systematic biopsy combined with targeted biopsy in detecting clinically significant prostate cancer.

Objectives: This retrospective study assessed the diagnostic accuracy of targeted biopsy (TB) and unilateral systematic biopsy in detecting clinically significant prostate cancer (csPCa) in 222 men with single magnetic resonance imaging (MRI) lesions (Prostate Imaging Reporting and Data System [PI-RADS] ≥ 3). Methods: Patients underwent multiparametric MRI and MRI/ultrasound fusion TB and 12-needle standard biopsy (SB) from September 2016 to June 2021. The study compared the diagnostic performance of TB + iSB (ipsilateral), TB + contralateral system biopsy (cSB) (contralateral), and TB alone for csPCa using the χ 2 test and analysis of variance. Results: Among 126 patients with csPCa (ISUP ≥ 2), detection rates for TB + iSB, TB + cSB, and TB were 100, 98.90, and 100% for lesions, respectively. TB + iSB showed the highest sensitivity and negative predictive value. No significant differences in accuracy were found between TB + iSB and the gold standard for type 3 lesions (P = 1). For types 4-5, detection accuracy was comparable across methods (P = 0.314, P = 0.314, P = 0.153). TB had the highest positive needle count rate, with TB + iSB being second for type 3 lesions (4.08% vs 6.57%, P = 0.127). Conclusion: TB + iSB improved csPCa detection rates and reduced biopsy numbers, making it a viable alternative to TB + SB for single MRI lesions.

Hypoglycemic Effect of Rambutan (Nephelium lappaceum L.) Peel Polyphenols on Type 2 Diabetes Mice by Modulating Gut Microbiota and Metabolites.

SCOPE: Type 2 diabetes mellitus (T2DM) is a metabolic disease with a major global public health effect. Rambutan peel polyphenols (RPPs) have been reported to exert hypoglycemic activity. However, few studies have been explored from the viewpoint of gut microbiota and its metabolites. METHODS AND RESULTS: RPPs are administered by gavage to a mice model of T2DM established by using a high-fat diet combined with streptozotocin. It finds that RPPs treatment alleviates hyperglycemia symptoms by improving glucolipid metabolism and liver function. Immunohistochemistry indicates that the antihyperglycemic effect of RPPs is regulated by the IRS-1/PI3K/AKT/GSK3ß signaling pathway. RPPs treatment remodels the structure of gut microbiota (Odoribacter, Lachnospiraceae_NK4A136_group, Lactobacillus, Turicibacter, Erysipelatoclostridium, and Tuzzerella) and enriches the metabolites (RPPs-derived urolithins, short-chain fatty acids, dehydrocholic acid, (+)-catechin, dihydroberberine, pterostilbene, and artesunate) associated with diabetes regulation in T2DM mice. The effects of RPPs in ameliorating glycolipid metabolism disorders are correlated with differential gut microbiota and metabolites. CONCLUSION: The gut microbiota and its metabolites are key targets for the hypoglycemic effects of RPPs.

Xiao-Er-Kang-Du capsules regulate autophagy against the influenza B virus (Victoria strain) through the mTOR/ULK1/Beclin1/VPS34 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiao-er-kang-du (XEKD) capsule is a Chinese herbal formula used for treatment of upper respiratory tract infection caused by various viruses in pediatric patients in China. XEKD is used clinically for the treatment of influenza-like symptoms, including fever, chills, cough, stuffy and runny nose, headache, and sore throat, with remarkable efficacy. However, the pharmacologic mechanism of XEKD against influenza B virus (IBV) infection is unclear. AIM OF THE STUDY: The main purpose of the present work is to explore the curative effect as well as possible mechanisms of XEKD against influenza B virus (IBV) (Victoria strain). MATERIALS AND METHODS: Both in vivo and in vitro experiments were performed to confirm the antiviral properties of XEKD. High-performance liquid chromatography was used to analyze the active components and assess the stability of XEKD. In addition, the mechanism of action of XEKD against IBV (Victoria) was investigated by western blot, immunofluorescence, and immunohistochemical analyses, in addition to confocal fluorescence microscopy. RESULTS: The findings revealed that XEKD demonstrated antiviral effects against IBV infection in both in vivo and in vitro via the mTOR/ULK1/Beclin1/VPS34 pathway and promote cellular autophagy to mitigate IBV-induced lung tissue damage. The results of this work are expected to lead to a deeper understanding of the mechanism underlying the effect of the XEKD capsule against IBV infections. CONCLUSIONS: IBV infection was found to inhibit autophagy, which exacerbated inflammatory damage. XEKD regulates autophagy through the mTOR/ULK1/Beclin1/VPS34 pathway and exerts antiviral effects, thereby laying a foundation for further development of XEKD as a potential therapeutic against IBV infection.

Exposure to per- and polyfluoroalkyl substances is associated with impaired cardiovascular health: a cross-sectional study.

Background: Per- and polyfluoroalkyl substance (PFAS) exposure and cardiovascular disease are controversial. We aimed to assess the association between serum PFAS exposure and cardiovascular health (CVH) in U.S. adults. Methods: We analyzed serum PFAS concentration data of U.S. adults reported in the National Health and Nutrition Examination Survey (NHANES) study (2005-2018). We employed two weighted logistic regression models and a restricted cubic spline (RCS) to examine the association between each PFAS and impaired CVH (defined as moderate and low CVH). Quantile g-computation (Qgcomp) and weighted quantile sum (WQS) analysis were used to estimate the effects of mixed exposures to PFASs on impaired CVH. Results: PFAS were associated with an increased risk of impaired CVH (ORPFNA: 1.40, 95% CI: 1.09, 1.80; ORPFOA: 1.44, 95% CI: 1.10, 1.88; ORPFOS: 1.62, 95% CI: 1.25, 2.11). PFOA and PFOS exhibited nonlinear relationships with impaired CVH. Significant interactions were observed for impaired CVH between race/ethnicity and PFHxS (p = 0.02), marital status and PFOA (p = 0.03), and both marital status and race/ethnicity with PFOS (p = 0.01 and p = 0.02, respectively). Analysis via WQS and Qgcomp revealed that the mixture of PFAS was positively associated with an increased risk of impaired CVH. Conclusion: PFNA, PFOA, and PFOS exposure are associated with an increased risk of impaired CVH in U.S. adults. Race/ethnicity and marital status may influence CVH. Reducing PFAS exposure could alleviate the burden of disease associated with impaired CVH.

M2Trans: Multi-Modal Regularized Coarse-to-Fine Transformer for Ultrasound Image Super-Resolution.

Ultrasound image super-resolution (SR) aims to transform low-resolution images into high-resolution ones, thereby restoring intricate details crucial for improved diagnostic accuracy. However, prevailing methods relying solely on image modality guidance and pixel-wise loss functions struggle to capture the distinct characteristics of medical images, such as unique texture patterns and specific colors harboring critical diagnostic information. To overcome these challenges, this paper introduces the Multi-Modal Regularized Coarse-to-fine Transformer (M2Trans) for Ultrasound Image SR. By integrating the text modality, we establish joint image-text guidance during training, leveraging the medical CLIP model to incorporate richer priors from text descriptions into the SR optimization process, enhancing detail, structure, and semantic recovery. Furthermore, we propose a novel coarse-to-fine transformer comprising multiple branches infused with self-attention and frequency transforms to efficiently capture signal dependencies across different scales. Extensive experimental results demonstrate significant improvements over state-of-the-art methods on benchmark datasets, including CCA-US, US-CASE, and our newly created dataset MMUS1K, with a minimum improvement of 0.17dB, 0.30dB, and 0.28dB in terms of PSNR. Our code and dataset will be available at: https://github.com/eezkni/M2Trans.

How does high hydrostatic pressure treatment improve the esterification of quinoa (Chenopodium quinoa Willd.) starch?

High hydrostatic pressure (HHP) treatment was combined with octenyl succinic anhydride (OSA) modification of quinoa starch (QS) to improve esterification efficiency. The modified QS was used as a stabilizer to prepare a Pickering emulsion. The results showed that the HHP treatment disrupted the morphology and crystalline structure of QS, exposed numerous hydrophilic hydroxyl groups, and added esterification reaction sites. The degree of substitution (DS) and esterification efficiency (RE) of OSA-HHP-QS were significantly (p < 0.05) increased compared with OSA-QS. In addition, the short-range ordering, relative crystallinity, and thermal stability of OSA-HHP-QS decreased with increasing treatment pressure. Except for OSA-HHP200-QS, the starch granules treated at 200 MPa were annealed, resulting in molecular recrystallization. The Contact angle, emulsion stability index (ESI), and emulsion activity index (EAI) indicated that the emulsions stabilized with OSA-HHP-QS were highly stable. Therefore, HHP can be used as a novel technology to assist OSA modified starches in stabilizing Pickering emulsions.

Profiles of differential expression of miRNAs in the late stage of red blood cell preservation and their potential roles.

OBJECTIVE: To detect the differentially expressed regulatory miRNAs in the late stage of red blood cell (RBC) preservation and predict their roles. METHODS: Suspended RBCs with different storage periods of 35 day, 42 day, and 50 day were collected for routine blood tests, RNA extraction, and preparation of small RNA sequencing libraries. The constructed libraries were sequenced and the biological functions of differential miRNAs in RBCs in the late storage were analyzed by bioinformatics. RESULTS: Routine indicators of RBCs in the late stage were not significantly affected by preservation time. The Pearson correlation analysis performing on RBC miRNAs with different storage days revealed that RBC miRNAs changed with the increase of storage days. RBC miRNAs from day 35 (D35), day 42 (D42) and day 50 (D50) showed significant differences (P < 0.05). Compared RBC miRNAs from D42 with these from D35, there were 690 up-regulated miRNAs and 82 down-regulated miRNAs; compared RBC miRNAs from D50 with these from D35, there were 638 up-regulated miRNAs and 123 down-regulated miRNAs; compared RBC miRNAs from D42 with these from D50, there were 271 up-regulated miRNAs and 515 down-regulated miRNAs. GO enrichment analysis of target genes of differential miRNAs were mainly involved in cell metabolism, biosynthesis, protein modification, gene expression and transcriptional regulation of biological processes. KEGG pathway enrichment analysis of miRNA target genes showed that differential miRNA target genes were closely related to pathways in cancer. CONCLUSION: MiRNAs were differentially expressed in the late stage of RBC preservation, and may be involved in various biological processes, especially cancer.

Preliminary establishment of genetic transformation system for embryogenic callus of Acer truncatum 'Lihong'.

Introduction: Acer truncatum Bunge, belonging to the Acer genus in the Aceraceae family, is a commonly planted afforestation species across China, Japan, Korea, Europe, and North America. Renowned for its vibrant fall colors, it holds significant ecological and ornamental value. Methods: In this study, Acer truncatum ' Lihong ' was used as the research object. Starting from the callus induction of explants, the embryogenic callus of Acer truncatum 'Lihong' was obtained by systematically optimizing the medium and culture conditions. Then, the candidate gene AtrGST894 screened by transcriptome sequencing was transformed into embryogenic callus by Agrobacterium-mediated transformation. The genetic transformation system of Acer truncatum 'Lihong' embryogenic callus was initially established by continuously adjusting the conditions of Agrobacterium tumefaciens infection receptor materials, thus laying a material foundation for the study of the molecular regulation mechanism of Acer truncatum 'Lihong' leaf color, and also preparing for the later molecular improvement breeding of Acer truncatum. Therefore, this study has important theoretical and practical significance. Results: The results showed that the best medium for callus induction of Acer truncatum was 1/2MS+2 mg/L 2,4-D+0.3 mg/L 6-BA+0.5 mg/L NAA; The embryogenic callus induction medium of Acer truncatum was 1/2MS+3.0mg/L 6-BA+2.0mg/L TDZ+0.5mg/L IBA+0.1mg/L GA3; The proliferation medium of embryogenic callus of Acer truncatum was WPM+1.0mg/L TDZ+0.5mg/L IBA+0.1mg/L GA3+3mg/L 6-BA+1.0mg/L KT; The infection experiment of Agrobacterium tumefaciens on the embryogenic callus of Acer truncatum showed that the best antibacterial medium was WPM+30g/L sucrose+8g/L agar+0.5g/L acid-hydrolyzed casein+0.2mg/L KT+1.0 mg/L TDZ+0.5 mg/L IBA+0.1 mg/L GA3+200mmol/L carboxybenzyl+200mg/L cephalosporin, and then WPM+30g/L sucrose+8g/L agar+0.5g/L acid-hydrolyzed casein+0.2mg/L KT+1.0 mg/L TDZ+0.5 mg/L IBA+0.1 mg/L GA3+300mmol/L carboxybenzyl+200mg/L cephalosporin+25mg/L hygromycin. Screening medium screening, The obtained embryogenic callus browning rate, pollution rate and mortality rate were the lowest, and maintained vigorous growth. Discussion: The embryogenic callus was used as the infection material to verify that we successfully transferred the target gene into the embryogenic callus, which means that the genetic transformation system of Acer truncatum embryogenic callus was partially completed, and the infection process could be effectively inhibited. Although there was partial browning, it could continue to proliferate. Therefore, in future experiments, the focus is still to continue to verify the optimal conditions for optimizing the genetic transformation of Acer truncatum embryogenic callus and to solve the problems of difficulty in embryonic callus germination.

The risk of ovarian cancer in hormone replacement therapy users: a systematic review and meta-analysis.

Background: With the increasing use of hormone replacement therapy (HRT), there is a need to understand its impact on the occurrence of female malignant tumors. This systematic review and meta-analysis aimed to assess the risk of ovarian cancer associated with HRT and its related risk factors. Methods: PUBMED, OVID, Embase, Cochrane, and Web of Science were searched from 1980 to April 2022 to identify studies on the risk of ovarian cancer and hormone replacement therapy. The random-effects model was used to estimate the pooled risk of HRT in ovarian cancer, both in cohort studies and case-control studies. Additionally, the analysis examined the outcomes associated with different types of estrogen plus progesterone regimens. Meta-regression and sensitive analysis were performed to evaluate the heterogeneity. Results: 21 cohort studies (involving 15,313 cases and 4,564,785 participants) and 30 case-control studies (including 18,738 cases and 57,747 controls) were analyzed. The pooled risks of ovarian cancer for HRT users were 1.20 (95% confidence interval [CI] 1.01-1.44) from cohort studies and 1.13 (95%CI 1.04-1.22) from case-control studies. However, after restricting the study period to recent decades, the significant results indicating a higher risk disappeared in cohort studies conducted after 2010 and in case-control studies conducted after 2006. Furthermore, the continuous use of estrogen-progesterone replacement therapy (EPRT) was associated with a risk comparable to that of sequential use. Subgroup analysis showed that both estrogen replacement treatment (ERT) and EPRT had minor risks; The risk further increased with prolonged exposure time, particularly for durations exceeding 10 years. Additionally, serous ovarian cancer appeared to be more susceptible than other pathological types. Conclusion: The risk of ovarian cancer associated with HRT has been decreasing over time. However, ERT may increase this risk, particularly when used for an extended period. It is recommended that long-time users consider continuous EPRT as a safer alternative. Systematic review registration: www.crd.york.ac.uk/prospero/, identifier CRD42022321279.

In Silico Screening of Bioactive Peptides in Stout Beer and Analysis of ACE Inhibitory Activity.

Stout beer was selected as the research object to screen angiotensin-converting enzyme (ACE) inhibitory peptides. The peptide sequences of stout beer were identified using ultra-performance liquid chromatography-quadrupole-Orbitrap mass spectrometry with de novo, and 41 peptides were identified with high confidence. Peptide Ranker was used to score the biological activity and six peptides with a score ≥ 0.5 were screened to predict their potential ACE inhibitory (ACEI) activity. The toxicity, hydrophilicity, absorption, and excretion of these peptides were predicted. In addition, molecular docking between the peptides and ACE revealed a significant property of the peptide DLGGFFGFQR. Furthermore, molecular docking conformation and molecular dynamics simulation revealed that DLGGFFGFQR could be tightly bound to ACE through hydrogen bonding and hydrophobic interaction. Lastly, the ACEI activity of DLGGFFGFQR was confirmed using in vitro evaluation and the IC50 value was determined to be 24.45 µM.

Weight-adjusted waist index is an independent predictor of all-cause and cause-specific mortality in patients with asthma.

BACKGROUND: There is a close relationship between obesity and the occurrence of asthma.The weight-adjusted waist index (WWI) is a relatively novel anthropometric parameter that reflects obesity. OBJECTIVE: We aimed to explore the association between WWI and mortality in the asthma population. METHODS: We included adult with asthma from NHANES 1999-2018. WWI = Waist circumference (cm)/square root of body weight (kg). Current asthma was determined by the participant's responses in standardized questionnaires. All-cause, cardiovascular disease (CVD), cancer, and respiratory disease mortality information was obtained by prospectively matching these data to the National Death Index. Multivariate-adjusted Cox proportional hazards regression analyses, Kaplan Meier survival analyses, restricted cubic spline (RCS) analyses, stratified analyses, and sensitivity analyses were used to clarify these associations. RESULTS: A total of 101,316 participants were included in the study, and 3223 were diagnosed with asthma.WWI was independently and positively associated with all-cause and all factor-specific mortality in asthma. In fully adjusted models, each unit increase in WWI was associated with 43 % (hazard ratio [HR] and 95 % confidence interval [CI] = 1.43 [1.25,1.64], p < 0.0001), 58 % (1.58 [1.25, 1.99], p < 0.001), 50 % (1.50 [1.19, 1.90], p < 0.001), and 79 % (1.79 [1.34, 2.39], p < 0.0001) increased all-cause, CVD, cancer, and respiratory disease mortality, respectively. RCS analyses showed largely linear associations between WWI and all mortality risks. Stratified analyses indicated that these associations were influenced by multiple factors, and that age was consistently the effect modifier across all associations. CONCLUSIONS: WWI is an independent predictor of all-cause, CVD, cancer, and respiratory-related mortality in the adult asthma population. These findings highlight that WWI may have novel prognostic value as a simple and easily accessible obesity parameter in asthma patients.

A Prediction Model for Assessing the Efficacy of Thermal Ablation in Treating Benign Thyroid Nodules ≥ 2 cm: A Multi-Center Retrospective Study.

OBJECTIVES: To develop and validate a prediction model utilizing clinical and ultrasound (US) data for preoperative assessment of efficacy following US-guided thermal ablation (TA) in patients with benign thyroid nodules (BTNs) ≥ 2 cm. MATERIALS AND METHODS: We retrospectively assessed 962 patients with 1011 BTNs who underwent TA at four tertiary centers between May 2018 and July 2022. Ablation efficacy was categorized into therapeutic success (volume reduction rate [VRR] > 50%) and non-therapeutic success (VRR ≤ 50%). We identified independent factors influencing the ablation efficacy of BTNs ≥ 2 cm in the training set using multivariate logistic regression. On this basis, a prediction model was established. The performance of model was further evaluated by discrimination (area under the curve [AUC]) in the validation set. RESULTS: Of the 1011 nodules included, 952 (94.2%) achieved therapeutic success at the 12-month follow-up after TA. Independent factors influencing VRR > 50% included sex, nodular composition, calcification, volume, and largest diameter (all p < 0.05). The prediction equation was established as follows: p = 1/1 + Exp∑[8.113 -2.720 × (if predominantly solid) -2.790 × (if solid) -1.275 × (if 10 mL < volume ≤ 30mL) -1.743 × (if volume > 30 mL) -1.268 × (if with calcification) -2.859 × (if largest diameter > 3 cm) +1.143 × (if female)]. This model showed great discrimination, with AUC of 0.908 (95% confidence interval [CI]: 0.868-0.947) and 0.850 (95% CI: 0.748-0.952) in the training and validation sets, respectively. CONCLUSIONS: A clinical prediction model was successfully developed to preoperatively predict the therapeutic success of BTNs larger than 2 cm in size following US-guided TA. This model aids physicians in evaluating treatment efficacy and devising personalized prognostic plans.

Three-Year Outcomes of 6-Month Paliperidone Palmitate in Adults With Schizophrenia: An Open-Label Extension Study of a Randomized Clinical Trial.

Importance: Long-acting injectable (LAI) antipsychotics have the potential to improve adherence and symptom control in patients with schizophrenia, promoting long-term recovery. Paliperidone palmitate (PP) once every 6 months is the first and currently only LAI antipsychotic with an extended dosing interval of 6 months. Objective: To assess long-term outcomes of PP received once every 6 months in adults with schizophrenia. Design, Setting, and Participants: In a 2-year open-label extension (OLE) study of a 1-year randomized clinical trial (RCT), eligible adults with schizophrenia could choose to continue PP every 6 months if they had not experienced relapse after receiving PP once every 3 or 6 months in the 1-year, international, multicenter, double-blind, randomized noninferiority trial. The present analysis focused on patients receiving PP every 6 months in the double-blind trial through the OLE study (November 20, 2017, to May 3, 2022). Intervention: Patients received a dorsogluteal injection of PP on day 1 and once every 6 months up to month 30. Main Outcomes and Measures: End points included assessment of relapse and change from the double-blind trial baseline to the OLE end point in Positive and Negative Syndrome Scale (PANSS) total and subscale, Clinical Global Impression-Severity (CGI-S) Scale, and Personal Social Performance (PSP) Scale scores. Treatment-emergent adverse events (TEAEs), injection site evaluations, and laboratory tests were also assessed. Results: Among 121 patients (83 [68.6%] male), mean (SD) age at baseline was 38.6 (11.24) years and mean (SD) duration of illness was 11.0 (9.45) years. At screening of the double-blind study, 101 patients (83.5%) were taking an oral antipsychotic and 20 (16.5%) were taking an LAI antipsychotic. Altogether, 5 of 121 patients (4.1%) experienced relapse during the 3-year follow-up; reasons for relapse were psychiatric hospitalization (2 [1.7%]), suicidal or homicidal ideation (2 [1.7%]), and deliberate self-injury (1 [0.8%]). Patients treated with PP every 6 months were clinically and functionally stable, and outcomes were well maintained, evidenced by stable scores on the PANSS (mean [SD] change, -2.6 [9.96] points), CGI-S (mean [SD] change, -0.2 [0.57] points), and PSP (mean [SD] change, 3.1 [9.14] points) scales over the 3-year period. In total, 101 patients (83.5%) completed the 2-year OLE. At least 1 TEAE was reported in 97 of 121 patients (80.2%) overall; no new safety or tolerability concerns were identified. Conclusions and Relevance: In a 2-year OLE study of a 1-year RCT, results supported favorable long-term outcomes of PP once every 6 months for up to 3 years in adults with schizophrenia.

Mediated Mendelian randomization analysis to determine the role of immune cells in regulating the effects of plasma metabolites on childhood asthma.

Childhood asthma is a chronic inflammatory disease of the airways, the pathogenesis of which involves multiple factors including genetic predisposition, environmental exposure, and immune system regulation. To date, the causal relationships between immune cells, plasma metabolites, and childhood asthma remain undetermined. Therefore, we aim to utilize the Mendelian randomization approach to assess the causal relationships among immune cells, plasma metabolites, and childhood asthma. This study employed the Mendelian randomization approach to investigate how immune cells influenced the risk of childhood asthma by modulating the levels of plasma metabolites. Five Mendelian randomization methods-inverse variance weighted, weighted median, Mendelian randomization-Egger, simple mode, and weighted mode-were utilized to explore the causal relationships among 731 types of immune cells, 1400 plasma metabolites, and childhood asthma. The instrumental variables for the 731 immune cells and 1400 plasma metabolites were derived from a genome-wide association study meta-analysis. Additionally, sensitivity analyses were conducted to examine the robustness of the results, potential heterogeneity, and pleiotropy. The inverse variance weighted results indicated that HLA DR on dendritic cells (DC) is a risk factor for childhood asthma (OR: 1.08, 95% CI: 1.02-1.14). In contrast, HLA DR on DC acts as a protective factor against elevated catechol glucuronide levels (OR: 0.94, 95% CI: 0.91-0.98), while catechol glucuronide levels themselves serve as a protective factor for childhood asthma (OR: 0.73, 95% CI: 0.60-0.89). Thus, HLA DR on DC can exert a detrimental effect on childhood asthma through the negative regulation of catechol glucuronide levels. The mediating effect was 0.018, accounting for a mediation effect proportion of 23.4%. This study found that HLA DR on DC can exert a risk effect on childhood asthma through the negative regulation of catechol glucuronide levels, providing new strategies for the prevention and treatment of childhood asthma and guiding future research and clinical practice.

Emulsion gels prepared from Longzhua mushroom polysaccharides with self-gelling properties as ß-carotene carriers: Stability and in vitro digestibility of ß-carotene.

ß-Carotene is widely used in food systems because of its biological activity; however, ß-carotene has poor chemical stability and low bioavailability. Thus, researchers use encapsulated delivery systems to overcome these disadvantages. In this study, we prepared emulsion gels to encapsulate ß-carotene, using Longzhua mushroom polysaccharide (LMP), which can autonomously form weak gels. The LMP emulsion gel (LEG) exhibited a high water-holding capacity of up to 95.06 %. All samples showed adequate storage stability for 28 days. Increasing the polysaccharide content in the emulsion gel enhanced the encapsulation efficiency of ß-carotene (96.76 %-98.27 %), the release of free fatty acids (68.21 %-81.44 %), and the photostability (80.65 %-91.27 %), thermal stability (73.84 %-97.08 %), and bioaccessibility (18.28 %-30.26 %) of ß-carotene. In conclusion, LEG is a promising fat-soluble material that can be used for food-grade encapsulated delivery systems.

Role of high-frequency ultrasound in differentiating benign and malignant skin lesions: potential and limitations.

PURPOSE: This study examined the diagnostic value of high-frequency ultrasound (HFUS) features in differentiating between benign and malignant skin lesions. METHODS: A total of 1,392 patients with 1,422 skin lesions who underwent HFUS examinations were included in an initial dataset (cohort 1) to identify features indicative of malignancy. Qualitative clinical and HFUS characteristics were recorded for all lesions. To determine which HFUS and clinical features were suggestive of malignancy, univariable and multivariable logistic regression analyses were employed. The diagnostic performance of HFUS features combined with clinical information was evaluated. This assessment was validated using internal data (cohort 2) and multicenter external data (cohort 3). RESULTS: Features significantly associated with malignancy included age above 60 years; lesion location in the head, face, and neck or genital regions; changes in macroscopic appearance; crawling or irregular growth pattern; convex or irregular base; punctate hyperechogenicity; blood flow signals; and feeding arteries. The area under the receiver operating characteristic curve, sensitivity, and specificity of HFUS features combined with clinical information were 0.946, 92.5%, and 86.9% in cohort 1; 0.870, 93.1%, and 80.8% in cohort 2 (610 lesions); and 0.864, 86.2%, and 86.6% in cohort 3 (170 lesions), respectively. However, HFUS is not suitable for evaluating lesions less than 0.1 mm in thickness or lesions exhibiting surface hyperkeratosis. CONCLUSION: In a clinical setting, the integration of HFUS with clinical information exhibited good diagnostic performance in differentiating malignant and benign skin lesions. However, its utility was limited in evaluating extremely thin lesions and those exhibiting hyperkeratosis.

ChatGPT Combining Machine Learning for the Prediction of Nanozyme Catalytic Types and Activities.

The design of nanozymes with superior catalytic activities is a prerequisite for broadening their biomedical applications. Previous studies have exerted significant effort in theoretical calculation and experimental trials for enhancing the catalytic activity of nanozyme. Machine learning (ML) provides a forward-looking aid in predicting nanozyme catalytic activity. However, this requires a significant amount of human effort for data collection. In addition, the prediction accuracy urgently needs to be improved. Herein, we demonstrate that ChatGPT can collaborate with humans to efficiently collect data. We establish four qualitative models (random forest (RF), decision tree (DT), adaboost random forest (adaboost-RF), and adaboost decision tree (adaboost-DT)) for predicting nanozyme catalytic types, such as peroxidase, oxidase, catalase, superoxide dismutase, and glutathione peroxidase. Furthermore, we use five quantitative models (random forest (RF), decision tree (DT), Support Vector Regression (SVR), gradient boosting regression (GBR), and fully connected deep neuron network (DNN)) to predict nanozyme catalytic activities. We find that GBR model demonstrates superior prediction performance for nanozyme catalytic activities (R2 = 0.6476 for Km and R2 = 0.95 for Kcat). Moreover, an open-access web resource, AI-ZYMES, with a ChatGPT-based nanozyme copilot is developed for predicting nanozyme catalytic types and activities and guiding the synthesis of nanozyme. The accuracy of the nanozyme copilot's responses reaches more than 90% through the retrieval augmented generation. This study provides a new potential application for ChatGPT in the field of nanozymes.