Colonization of microbiota derived from Macaca fascicularis, Bama miniature pigs, beagle dogs, and C57BL/6J mice alleviates DSS-induced colitis in germ-free mice.

Fecal microbiota transplantation (FMT) is an innovative and promising treatment for inflammatory bowel disease (IBD), which is related to the capability of FMT to supply functional microorganisms to improve recipient gut health. Numerous studies have highlighted considerable variability in the efficacy of FMT interventions for IBD. Several factors, including the composition of the donor microorganisms, significantly affect the efficacy of FMT in the treatment of IBD. Consequently, identifying the functional microorganisms in the donor is crucial for enhancing the efficacy of FMT. To explore potential common anti-inflammatory bacteria with therapeutic implications for IBD, germ-free (GF) BALB/c mice were pre-colonized with fecal microbiota obtained from diverse donors, including Macaca fascicularis (MCC_FMT), Bama miniature pigs (BP_FMT), beagle dogs (BD_FMT), and C57BL/6 J mice (Mice_FMT). Subsequently, mice were treated with dextran sodium sulfate (DSS). As expected, the symptoms of colitis were alleviated by MCC_FMT, BP_FMT, BD_FMT, and Mice_FMT, as demonstrated by the prevention of an elevated disease activity index in mice. Additionally, the utilization of distinct donors protected the intestinal barrier and contributed to the regulation of cytokine homeostasis. Metagenomic sequencing data showed that the microbial community structure and dominant species were significantly different among the four groups, which may be linked to variations in the anti-inflammatory efficacy observed in the respective groups. Notably, Lactobacillus reuteri and Flavonifractor plautii were consistently present in all four groups. L. reuteri exhibited a significant negative correlation with IL-1ß, and animal studies further confirmed its efficacy in alleviating IBD, suggesting the presence of common functional bacteria across different donors that exert anti-inflammatory effects. This study provides essential foundational data for the potential clinical applications of FMT.IMPORTANCEDespite variations in efficacy observed among donors, numerous studies have underscored the potential of fecal microbiota transplantation (FMT) for managing inflammatory bowel disease (IBD), indicating the presence of shared anti-IBD bacterial species. In the present study, the collective anti-inflammatory efficacy observed across all four donor groups prompted the identification of two common bacterial species using metagenomics. A significant negative correlation between Lactobacillus reuteri and IL-1ß was revealed. Furthermore, mice gavaged with L. reuteri successfully managed the colitis challenge induced by dextran sodium sulfate (DSS), suggesting that L. reuteri may act as an efficacious bacterium mediating shared anti-inflammatory effects among variable donors. This finding highlights the utilization of variable donors to screen FMT core bacteria, which may be a novel strategy for developing FMT applications.

Electroacupuncture activates the peroxisome proliferators-activated receptor pathway to improve the phenotype of cerebral palsy.

AIM: This study explores the efficacy of electroacupuncture (EA) in treating cerebral palsy (CP) in Sprague-Dawley (SD) pups, specifically CP animal models, and its molecular mechanisms. METHODS: Gait analysis and Y-maze were used to detect the improvement of motor ability and cognitive function of CP rats after EA treatment. Transcription sequencing was used to determine the key pathway for EA to improve the symptoms of CP. PPAR agonists were used to verify the causal relationship between the pathway and the improvement of CP phenotype. RESULTS: The motor ability and cognitive function of CP pups were improved after EA treatment. The results of transcriptome sequencing suggest that the improvement of CP phenotype may be caused by the activation of PPAR pathway. PPAR pathway is widely activated in the epithelium of CP pups treated with EA, which is verified by qPCR. Rosiglitazone (Ros), a PPAR agonist, can improve CP phenotype while activating PPAR pathway, which proves the causal relationship between PPAR pathway activation and CP phenotype improvement. CONCLUSION: Our study demonstrated behavioral improvements and enhanced cognitive functions in CP models after EA treatment by activating PPAR pathway, suggesting new perspectives for CP rehabilitation, and providing theoretical support for acupuncture treatment of CP.

Exploration of effective biomarkers for venous thrombosis embolism in Behçet's disease based on comprehensive bioinformatics analysis.

Behçet's disease (BD) is a multifaceted autoimmune disorder affecting multiple organ systems. Vascular complications, such as venous thromboembolism (VTE), are highly prevalent, affecting around 50% of individuals diagnosed with BD. This study aimed to identify potential biomarkers for VTE in BD patients. Three microarray datasets (GSE209567, GSE48000, GSE19151) were retrieved for analysis. Differentially expressed genes (DEGs) associated with VTE in BD were identified using the Limma package and weighted gene co-expression network analysis (WGCNA). Subsequently, potential diagnostic genes were explored through protein-protein interaction (PPI) network analysis and machine learning algorithms. A receiver operating characteristic (ROC) curve and a nomogram were constructed to evaluate the diagnostic performance for VTE in BD patients. Furthermore, immune cell infiltration analyses and single-sample gene set enrichment analysis (ssGSEA) were performed to investigate potential underlying mechanisms. Finally, the efficacy of listed drugs was assessed based on the identified signature genes. The limma package and WGCNA identified 117 DEGs related to VTE in BD. A PPI network analysis then selected 23 candidate hub genes. Four DEGs (E2F1, GATA3, HDAC5, and MSH2) were identified by intersecting gene sets from three machine learning algorithms. ROC analysis and nomogram construction demonstrated high diagnostic accuracy for these four genes (AUC: 0.816, 95% CI: 0.723-0.909). Immune cell infiltration analysis revealed a positive correlation between dysregulated immune cells and the four hub genes. ssGSEA provided insights into potential mechanisms underlying VTE development and progression in BD patients. Additionally, therapeutic agent screening identified potential drugs targeting the four hub genes. This study employed a systematic approach to identify four potential hub genes (E2F1, GATA3, HDAC5, and MSH2) and construct a nomogram for VTE diagnosis in BD. Immune cell infiltration analysis revealed dysregulation, suggesting potential macrophage involvement in VTE development. ssGSEA provided insights into potential mechanisms underlying BD-induced VTE, and potential therapeutic agents were identified.

Identifying gut microbiota with high specificity for ischemic stroke with large vessel occlusion.

Gut microbiota can regulate the metabolic and immunological aspects of ischemic stroke and modulate the treatment effects. The present study aimed to identify specific changes in gut microbiota in patients with large vessel occlusion (LVO) ischemic stroke and assess the potential association between gut microbiota and clinical features of ischemic stroke. A total of 63 CSVD patients, 64 cerebral small vessel disease (CSVD) patients, and 36 matching normal controls (NCs) were included in this study. The fecal samples were collected for all participants and analyzed for gut microbiota using 16S rRNA gene sequencing technology. The abundances of five gut microbiota, including genera Bifidobacterium, Butyricimonas, Blautia, and Dorea and species Bifidobacterium_longum, showed significant changes with high specificity in the LVO patients as compared to the NCs and CSVD patients. In LVO patients, the genera Bifidobacterium and Blautia and species Bifidobacterium_longum were significantly correlated with the National Institutes of Health Stroke Scale (NIHSS) scores at the admission and discharge of the patients. Serum triglyceride levels could significantly affect the association of the abundance of genus Bifidobacterium and species Bifidobacterium_longum with the NIHSS scores at admission and modified Rankin Scale (mRS) at discharge in LVO patients. The identification of five gut microbiota with high specificity were identified in the early stage of LVO stroke, which contributed to performed an effective clinical management for LVO ischemic stroke.

LINC01535 promotes hepatocellular carcinoma proliferation and metastasis by regulating the miR-214-3p/VASP axis.

Background: Emerging evidence has indicated that long noncoding RNAs (lncRNAs) are associated with the development and progression of several carcinomas, including hepatocellular carcinoma (HCC). However, the role of LINC01535 in HCC is still unknown. Materials and methods: In this study, RNA-seq, CCK-8, colony formation, wound healing, Transwell and tumor xenograft assays were used to explore the function of LINC01535 in the proliferation and metastasis of HCC in vitro and in vivo. Fluorescence in situ hybridization (FISH) assay, bioinformatics analysis, dual-luciferase assay, quantitative real-time polymerase chain reaction (qRT-PCR), and western blot analysis were used to reveal the interactions of LINC01535, miR-214-3p and VASP. Results: LINC01535 was overexpressed in HCC tissues and HCC cell lines. Gain- and loss-of-function studies revealed that LINC01535 could promote HCC cell proliferation, migration and invasion both in vitro and in vivo. In addition, upregulation of LINC01535 significantly decreased the expression of microRNA-214-3p (miR-214-3p), which was found closely associated with suppressing tumor progression. Moreover, VASP was identified as a direct downstream target gene of miR-214-3p. LINC01535 positively regulated VASP expression by sponging miR-214-3p, and VASP overexpression activated the PI3K/AKT signaling pathway and stimulated epithelial-to-mesenchymal transition (EMT) in HCC. Conclusions: Our study first found that LINC01535 promoted HCC progression by regulating its downstream target, the miR-214-3p/VASP axis, via the PI3K/AKT signaling pathway. The function and novel regulatory mechanism of LINC01535 may provide a valuable target for the diagnosis and treatment of HCC patients.

The clinical effects of Orff music therapy on children with autism spectrum disorder: a comprehensive evaluation.

Objective: This study aimed to investigate the clinical effects of Orff music therapy on children with Autism Spectrum Disorder (ASD) from the perspectives of parents, evaluators, and therapists. Methods: 93 children with ASD aged 3-6 years participated in the study. They were divided into an observation group (n = 48) receiving comprehensive rehabilitation intervention including Orff music therapy, and a control group (n = 45) receiving only comprehensive rehabilitation intervention. The Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and Psycho-educational Profile-3rd edition (PEP-3) were used for assessments before and after the intervention. Results: There were no significant demographic differences between the two groups. Both groups showed significant improvements in Sensory, Relating, Language, CVP, EL, RL, VMI, AE, SR, and CARS scores at T1, T2, and T3 (T1 vs. T2, T2 vs. T3, T1 vs. T3) (all p < 0.05). The observation group demonstrated significant changes in Body and Object use and FM, while the control group showed some changes in these domains. Social and self-help, GM, CMB, and CVB also significantly improved in both groups after 6 months of intervention (all p < 0.05). In terms of different time intervals, the observation group showed greater improvements in Sensory, Relating, Language, CARS scores, EL, RL, and SR compared to the control group (all p < 0.05). The improvement levels in Body and Object use, CVP, FM, VMI, and AE did not differ significantly between the two groups in the T1-T2 interval, but were significantly higher in the observation group in the T2-T3 and T1-T3 intervals (all p < 0.05). The magnitude of changes in Social and self-help, GM, CMB, and CVB did not differ significantly between the groups. Conclusion: Orff music therapy showed significant improvements in language expression, language comprehension, social skills, cognitive abilities, imitation abilities, emotional expression and fine motor in children with ASD. These findings provide support for the use of Orff music therapy as an effective intervention for children with ASD.

Facility for spectral radiance calibration at low light level.

The spectral radiance measurement at daytime level can be realized with high accuracy, while it's difficult when the spectral radiance is at nighttime level. We design a spectral radiance calibration facility which has the characteristics of completely unchanged spectrum over 3 orders of magnitude and approximately unchanged spectrum for about 6 orders of magnitude. It combines a spectral radiance light source, a precision aperture and a white diffuser together, make it easy to reproduce the spectral radiance at 380 nm from 4 × 10-9 W/(m2·sr·nm) to 4 × 10-3 W/(m2·sr·nm). The facility can be easily used to calibrate a spectroradiometer at nighttime level. When the spectral radiance from 380 nm to 780 nm is around 1 × 10-7W/(m2·sr·nm), the calibration uncertainty of the spectroradiometer is 0.87%∼1.0% (k = 1).

[Research progress on the dynamic role and intervention value of autophagy in neonatal hypoxic-ischemic brain damage].

The repair of the nervous system after hypoxic-ischemic brain damage (HIBD) in neonates lacks specific therapeutic approaches, posing a challenge and hot topic in the medical field. Autophagy, as a cellular self-repair mechanism, plays a role through different signaling pathways at different stages, yet its specific roles and mechanisms in different stages of HIBD remain unclear. This article reviews the recent research advancements on autophagy in different neonatal HIBD stages: heightened autophagic activity manifests during the acute hypoxic-ischemic phase, with its neuroprotective or deleterious impact subject to ongoing debate; during the subacute and chronic phases, autophagy exert dual effects on neuronal death and repair; in sequelae period, autophagy-related studies are still insufficient, but the expression levels of autophagy-related genes (ATG) in children with cerebral palsy suggest both positive and negative aspects of autophagy post-HIBD. Collectively, optimal autophagic flux facilitates the elimination of detrimental substrates and toxic proteins, thereby engendering neuroprotection. Further studies on the roles and mechanisms of autophagy in HIBD therapy holds promise for devising efficacious preventative and therapeutic strategies rooted in autophagy, and to improve the survival rate and quality of life of the children.

Assessment of the role of false-positive alerts in computer-aided polyp detection for assistance capabilities.

BACKGROUND AND AIM: False positives (FPs) pose a significant challenge in the application of artificial intelligence (AI) for polyp detection during colonoscopy. The study aimed to quantitatively evaluate the impact of computer-aided polyp detection (CADe) systems' FPs on endoscopists. METHODS: The model's FPs were categorized into four gradients: 0-5, 5-10, 10-15, and 15-20 FPs per minute (FPPM). Fifty-six colonoscopy videos were collected for a crossover study involving 10 endoscopists. Polyp missed rate (PMR) was set as primary outcome. Subsequently, to further verify the impact of FPPM on the assistance capability of AI in clinical environments, a secondary analysis was conducted on a prospective randomized controlled trial (RCT) from Renmin Hospital of Wuhan University in China from July 1 to October 15, 2020, with the adenoma detection rate (ADR) as primary outcome. RESULTS: Compared with routine group, CADe reduced PMR when FPPM was less than 5. However, with the continuous increase of FPPM, the beneficial effect of CADe gradually weakens. For secondary analysis of RCT, a total of 956 patients were enrolled. In AI-assisted group, ADR is higher when FPPM ≤ 5 compared with FPPM > 5 (CADe group: 27.78% vs 11.90%; P = 0.014; odds ratio [OR], 0.351; 95% confidence interval [CI], 0.152-0.812; COMBO group: 38.40% vs 23.46%, P = 0.029; OR, 0.427; 95% CI, 0.199-0.916). After AI intervention, ADR increased when FPPM ≤ 5 (27.78% vs 14.76%; P = 0.001; OR, 0.399; 95% CI, 0.231-0.690), but no statistically significant difference was found when FPPM > 5 (11.90% vs 14.76%, P = 0.788; OR, 1.111; 95% CI, 0.514-2.403). CONCLUSION: The level of FPs of CADe does affect its effectiveness as an aid to endoscopists, with its best effect when FPPM is less than 5.

[Recent research on home rehabilitation and nursing for spinal muscular atrophy]. / è„Šé«“æ€§è‚ŒèŽç¼©ç—‡å®¶åº­åº·å¤ä¸ŽæŠ¤ç†çš„ç ”ç©¶è¿›å±•.

Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder. With the emergence of disease-modifying therapies, the prognosis of SMA has significantly improved, drawing increased attention to the importance of home rehabilitation and nursing management. Long-term, standardized home rehabilitation and nursing can delay the progression of SMA, enhance the psychological well-being, and improve the quality of life of both patients and caregivers. This article provides an overview of the goals of home rehabilitation, basic functional training methods, respiratory management, and nutritional management for SMA patients, as well as psychological health issues, emphasizing the significance of obtaining appropriate home rehabilitation and support during the care process.

Multi-step validation of a Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis prediction system integrating multi-modal data: A multi-center study.

BACKGROUND AND STUDY AIMS: The impact of various categories of information on the prediction of Post Endoscopic Retrograde Cholangiopancreatography Pancreatitis (PEP) remains uncertain. We aimed to comprehensively investigate the risk factors associated with PEP by constructing and validating a model incorporating multi-modal data through multiple steps. PATIENTS AND METHODS: A total of 1,916 cases underwent ERCP were retrospectively collected from multiple centers for model construction. Through literature research, 49 electronic health record (EHR) features and one image feature related to PEP were identified. The EHR features were categorized into baseline, diagnosis, technique, and prevent strategies, covering pre-ERCP, intra-ERCP, and peri-ERCP phases. We first incrementally constructed models 1-4 incorporating these four feature categories, then added the image feature into models 1-4 and developed models 5-8. All models underwent testing and comparison using both internal and external test sets. Once the optimal model was selected, we conducted comparison among multiple machine learning algorithms. RESULTS: Compared with model 2 incorporating baseline and diagnosis features, adding technique and prevent strategies (model 4) greatly improved the sensitivity (63.89% vs 83.33%, p<0.05) and specificity (75.00% vs 85.92%, p<0.001). Similar tendency was observed in internal and external tests. In model 4, the top three features ranked by weight were previous pancreatitis, NSAIDS, and difficult cannulation. The image-based feature has the highest weight in model 5-8. Lastly, model 8 employed Random Forest algorithm showed the best performance. CONCLUSIONS: We firstly developed a multi-modal prediction model for identifying PEP with clinical-acceptable performance. The image and technique features are crucial for PEP prediction.

Validation of artificial intelligence-based bowel preparation assessment in screening colonoscopy (with video).

BACKGROUND AND AIMS: Accurate bowel preparation assessment is essential for determining colonoscopy screening intervals. Patients with suboptimal bowel preparation are at a high risk of missing >5 mm adenomas and should undergo an early repeat colonoscopy. In this study, we used artificial intelligence (AI) to evaluate bowel preparation and validated the ability of the system to accurately identify patients who are at high risk of having >5 mm adenomas missed due to inadequate bowel preparation. METHODS: This prospective, single-center, observational study was conducted at the Eighth Affiliated Hospital, Sun Yat-sen University, from October 8, 2021, to November 9, 2022. Eligible patients who underwent screening colonoscopy were consecutively enrolled. The AI assessed bowel preparation using the e-Boston Bowel Preparation Scale (e-BBPS) while endoscopists made evaluations using BBPS. If both BBPS and e-BBPS deemed preparation adequate, the patient immediately underwent a second colonoscopy; otherwise, the patient underwent bowel re-cleansing before the second colonoscopy. RESULTS: Among the 393 patients, 72 adenomas >5 mm in size were detected; 27 adenomas >5 mm in size were missed. In unqualified-AI patients, the >5 mm adenoma miss rate (AMR) was significantly higher than in qualified-AI patients (35.71% vs 13.19% [P = .0056]; odds ratio [OR], .2734 [95% CI, .1139-.6565]), as were the AMR (50.89% vs 20.79% [P < .001]; OR, .2532 [95% CI, .1583-.4052]) and >5 mm polyp miss rate (35.82% vs 19.48% [P = .0152]; OR, .4335 [95% CI, .2288-.8213]). CONCLUSIONS: This study confirmed that patients classified as inadequate by AI exhibited an unacceptable >5 mm AMR, providing key evidence for implementing AI in guiding bowel re-cleansing and potentially standardizing future colonoscopy screening. (Clinical trial registration number: NCT05145712.).

Current understanding of children's head shape and its impact on health: a cross-sectional study among pediatric medical staff in China.

Background: Head shape problems are common in infancy and early childhood, and thus their early identification and management can benefit the health of children. This study aimed to investigate pediatric healthcare professionals' existing knowledge of children's head shape abnormalities and their associated effects in China, providing guidelines for future clinical interventions, training, and interdisciplinary collaboration. Methods: We conducted a survey among pediatric medical staff, encompassing various age groups, genders, hospitals, and professional levels. The electronic questionnaire queried respondents' basic information, knowledge pertaining to head shape issues, diagnosis and treatment approaches, and the clinical development status of head shape problems. All surveys and data collection were conducted anonymously. Results: A total of 214 valid questionnaires were collected. Differences in the level of understanding among medical staff regarding head shape issues were observed. Medical staff in tertiary care facilities showed the highest proficiency in diagnosing and treating positional plagiocephaly and cranial asymmetry (P<0.05), while those in primary care facilities exhibited the lowest competency in diagnosing head shape abnormalities (P<0.05). Most medical staff had a partial understanding of specific aspects of head shape issues, such as identifying high-risk individuals (n=144, 67.29%), making diagnoses (n=176, 82.24%), and understanding the consequences (n=151, 70.56%), with no significant differences across medical facilities of various levels. Additionally, 99.07% (n=212) of the medical staff believed that head shape measurements should be included as a routine component of pediatric physical examinations, and 75.23% (n=161) incorporate head shape assessment as part of their routine physical examination. Furthermore, 91.12% (n=195) of the medical staff received consultations on children's head shape issues, with a higher prevalence in secondary and tertiary care facilities. Finally, 93.97% (n=201) of the participants expressed the need for further education and knowledge on pediatric head shape, with no significant differences across medical facilities of various levels. Conclusions: There is a limited understanding among medical personnel in China regarding children's head shape issues. Therefore, it is imperative to enhance training and educational initiatives for medical staff in China, with the goal of enhancing their awareness and knowledge regarding children's head shape problems.

Identification of key biomarkers for predicting CAD progression in inflammatory bowel disease via machine-learning and bioinformatics strategies.

The study aimed to identify the biomarkers for predicting coronary atherosclerotic lesions progression in patients with inflammatory bowel disease (IBD). Related transcriptome datasets were seized from Gene Expression Omnibus database. IBD-related modules were identified via Weighted Gene Co-expression Network Analysis. The 'Limma' was applied to screen differentially expressed genes between stable coronary artery disease (CAD) and acute myocardial infarction (AMI). Subsequently, we employed protein-protein interaction (PPI) network and three machine-learning strategies to further screen for candidate hub genes. Application of the receiver operating characteristics curve to quantitatively evaluate candidates to determine key diagnostic biomarkers, followed by a nomogram construction. Ultimately, we performed immune landscape analysis, single-gene GSEA and prediction of target-drugs. 3227 IBD-related module genes and 570 DEGs accounting for AMI were recognized. Intersection yielded 85 shared genes and mostly enriched in immune and inflammatory pathways. After filtering through PPI network and multi-machine learning algorithms, five candidate genes generated. Upon validation, CTSD, CEBPD, CYP27A1 were identified as key diagnostic biomarkers with a superior sensitivity and specificity (AUC > 0.8). Furthermore, all three genes were negatively correlated with CD4+ T cells and positively correlated with neutrophils. Single-gene GSEA highlighted the importance of pathogen invasion, metabolism, immune and inflammation responses during the pathogenesis of AMI. Ten target-drugs were predicted. The discovery of three peripheral blood biomarkers capable of predicting the risk of CAD proceeding into AMI in IBD patients. These identified biomarkers were negatively correlated with CD4+ T cells and positively correlated with neutrophils, indicating a latent therapeutic target.

Extracellular vesicles derived from Lactobacillus johnsonii promote gut barrier homeostasis by enhancing M2 macrophage polarization.

INTRODUCTION: Diarrheic disease is a common intestinal health problem worldwide, causing great suffering to humans and animals. Precise manipulation strategies based on probiotics to combat diarrheic diseases have not been fully developed. OBJECTIVES: The aim of this study was to investigate the molecular mechanisms by which probiotics manipulate macrophage against diarrheic disease. METHODS: Metagenome reveals gut microbiome profiles of healthy and diarrheic piglets. Fecal microbial transplantation (FMT) was employed to explore the causal relationship between gut microbes and diarrhea. The protective role of probiotics and their derived extracellular vesicles (EVs) was investigated in ETEC K88-infected mice. Macrophage depletion was performed to assess the role of macrophages in EVs against diarrhea. Execution of in vitro cell co-culture and transcriptome analyses elucidated the molecular mechanisms by which EVs modulate the macrophage and intestinal epithelial barrier. RESULTS: Escherichia coli was enriched in weaned diarrheic piglets, while Lactobacillus johnsonii (L. john) showed a negative correlation with Escherichia coli. The transmission of diarrheic illness symptoms was achieved by transferring fecal microbiota, but not metabolites, from diarrheic pigs to germ-free (GF) mice. L. john's intervention prevented the transmission of disease phenotypes from diarrheic piglets to GF mice. L. john also reduces the gut inflammation induced by ETEC K88. The EVs secreted by L. john demonstrated enhanced efficacy in mitigating the adverse impacts induced by ETEC K88 through the modulation of macrophage phenotype. In vitro experiments have revealed that EVs activate M2 macrophages in a manner that shuts down ERK, thereby inhibiting NLRP3 activation in intestinal epithelial cells. CONCLUSION: Our results reveal that intestinal microbiota drives the onset of diarrheic disease and that probiotic-derived EVs ameliorate diarrheic disease symptoms by modulating macrophage phenotypes. These findings can enhance the advancement of innovative therapeutic approaches for diarrheic conditions based on probiotic-derived EVs.

WSA-MP-Net: Weak-signal-attention and multi-scale perception network for microvascular extraction in optical-resolution photoacoustic microcopy.

The unique advantage of optical-resolution photoacoustic microscopy (OR-PAM) is its ability to achieve high-resolution microvascular imaging without exogenous agents. This ability has excellent potential in the study of tissue microcirculation. However, tracing and monitoring microvascular morphology and hemodynamics in tissues is challenging because the segmentation of microvascular in OR-PAM images is complex due to the high density, structure complexity, and low contrast of vascular structures. Various microvasculature extraction techniques have been developed over the years but have many limitations: they cannot consider both thick and thin blood vessel segmentation simultaneously, they cannot address incompleteness and discontinuity in microvasculature, there is a lack of open-access datasets for DL-based algorithms. We have developed a novel segmentation approach to extract vascularity in OR-PAM images using a deep learning network incorporating a weak signal attention mechanism and multi-scale perception (WSA-MP-Net) model. The proposed WSA network focuses on weak and tiny vessels, while the MP module extracts features from different vessel sizes. In addition, Hessian-matrix enhancement is incorporated into the pre-and post-processing of the input and output data of the network to enhance vessel continuity. We constructed normal vessel (NV-ORPAM, 660 data pairs) and tumor vessel (TV-ORPAM, 1168 data pairs) datasets to verify the performance of the proposed method. We developed a semi-automatic annotation algorithm to obtain the ground truth for our network optimization. We applied our optimized model successfully to monitor glioma angiogenesis in mouse brains, thus demonstrating the feasibility and excellent generalization ability of our model. Compared to previous works, our proposed WSA-MP-Net extracts a significant number of microvascular while maintaining vessel continuity and signal fidelity. In quantitative analysis, the indicator values of our method improved by about 1.3% to 25.9%. We believe our proposed approach provides a promising way to extract a complete and continuous microvascular network of OR-PAM and enables its use in many microvascular-related biological studies and medical diagnoses.

Silencing p75NTR regulates osteogenic differentiation and angiogenesis of BMSCs to enhance bone healing in fractured rats.

BACKGROUND: Fractures heal through a process that involves angiogenesis and osteogenesis but may also lead to non-union or delayed healing. Bone marrow mesenchymal stem cells (BMSCs) have been reported to play a pivotal role in bone formation and vascular regeneration and the p75 neurotrophin receptor (p75NTR) as being an important regulator of osteogenesis. Herein, we aim to determine the potential mediation of BMSCs by p75NTR in bone healing. METHODS: Rat BMSCs were identified by flow cytometry (FCM) to detect cell cycle and surface markers. Then transfection of si/oe-p75NTR was performed in BMSCs, followed by Alizarin red staining to detect osteogenic differentiation of cells, immunofluorescence double staining was performed to detect the expression of p75NTR and sortilin, co-immunoprecipitation (CO-IP) was conducted to analyze the interaction between p75NTR and sortilin, and EdU staining and cell scratch assay to assess the proliferation and migration of human umbilical vein endothelial cells (HUVECs). The expression of HIF-1α, VEGF, and apoptosis-related proteins were also detected. In addition, a rat fracture healing model was constructed, and BMSCs-si-p75NTR were injected, following which the fracture condition was observed using micro-CT imaging, and the expression of platelet/endothelial cell adhesion molecule-1 (CD31) was assessed. RESULTS: The results showed that BMSCs were successfully isolated, p75NTR inhibited apoptosis and the osteogenic differentiation of BMSCs, while si-p75NTR led to a decrease in sortilin expression in BMSCs, increased proliferation and migration in HUVECs, and upregulation of HIF-1α and VEGF expression. In addition, an interaction was observed between p75NTR and sortilin. The knockdown of p75NTR was found to reduce the severity of fracture in rats and increase the expression of CD31 and osteogenesis-related proteins. CONCLUSION: Silencing p75NTR effectively modulates BMSCs to promote osteogenic differentiation and angiogenesis, offering a novel perspective for improving fracture healing.

Identification of multiple plasma lipids as diagnostic biomarkers of hypercholesterolemia and the underlying mechanisms based on pseudo-targeted lipidomics.

RATIONALE: Hypercholesterolemia is an important risk factor for cardiovascular diseases and death. This study performed pseudo-targeted lipidomics to identify differentially expressed plasma lipids in hypercholesterolemia, to provide a scientific basis for the diagnosis and pathogenesis of hypercholesterolemia. METHODS: Pseudo-targeted lipidomic analyses of plasma lipids from 20 patients with hypercholesterolemia and 20 normal control subjects were performed using liquid chromatography-mass spectrometry. Differentially expressed lipids were identified by principal component analysis and orthogonal partial least squares discriminant analysis. Receiver operating characteristic curves were used to identify differentially expressed lipids with high diagnostic value. The Kyoto Encyclopedia of Genes and Genomes pathway database was used to identify enriched metabolic pathways. RESULTS: We identified 13 differentially expressed lipids in hypercholesterolemia using variable importance of projection > 1 and p < 0.05 as threshold parameters. The levels of eight sphingomyelins and cholesterol sulfate were higher and those of three triacylglycerols and lysophosphatidylcholine were reduced in hypercholesterolemia. Seven differentially expressed plasma lipids showed high diagnostic value for hypercholesterolemia. Functional enrichment analyses showed that pathways related to necroptosis, sphingolipid signaling, sphingolipid metabolism, and steroid hormone biosynthesis were enriched. CONCLUSIONS: This pseudo-targeted lipidomics study demonstrated that multiple sphingomyelins and cholesterol sulfate were differentially expressed in the plasma of patients with hypercholesterolemia. We also identified seven plasma lipids, including six sphingomyelins and cholesterol sulfate, with high diagnostic value.

Second Near-Infrared Macrophage-Biomimetic Nanoprobes for Photoacoustic Imaging of Neuroinflammation.

Neuroinflammation is a significant pathological event involving the neurodegenerative process associated with many neurological disorders. Diagnosis and treatment of neuroinflammation in its early stage are essential for the prevention and management of neurological diseases. Herein, we designed macrophage membrane-coated photoacoustic (PA) probes (MSINPs), with targeting specificities based on naturally existing target-ligand interactions for the early diagnosis of neuroinflammation. The second near-infrared dye, IR1061, was doped into silica as the core and was encapsulated with a macrophage membrane. In vitro as well as in vivo, the MSINPs could target inflammatory cells via the inflammation chemotactic effect. PA imaging was used to trace the MSINPs in a neuroinflammation mouse model and showed a great targeted effect of MSINPs in the prefrontal cortex. Therefore, the biomimetic nanoprobe prepared in this study offers a new strategy for PA molecular imaging of neuroinflammation, which can enhance our understanding of the evolution of neuroinflammation in specific brain regions.

Association between cardiometabolic index and depression: National Health and Nutrition Examination Survey (NHANES) 2011-2014.

BACKGROUND: Emerging evidence suggests a common pathophysiological basis for metabolic disorders and mental diseases. Despite the existence of reports suggesting a strong connection between dyslipidemia and depression, a comprehensive and reliable indicator to identify depression is still lacking. Cardiometabolic index (CMI) is an integrated index calculated from three vital metabolic indicators, including triglyceride (TG), high-density lipoprotein cholesterol (HDLC) and waist height ratio (WHtR). OBJECTIVE: This study aims to explore the association between CMI and depression. METHODS: Cross-sectional data of participants with complete information of CMI, depression, and other covariates were obtained from the National Health and Nutrition Examination Survey (NHANES). Weighted student's t-test and Chi-square test were used to identify the differences between two groups. Weighted multivariate logistic regression model, restricted cubic spline (RCS) regression analysis, subgroup analysis and interaction tests were conducted to explore the association between CMI and depression. Receiver operating curve (ROC) analysis and area under the curve (AUC) were also utilized to evaluate the performance of CMI in identifying depression. RESULTS: A positive correlation between CMI and depression was observed in 3794 participants included in the study, which was further confirmed to be non-linear via RCS regression analysis, with two significant inflection points being identified, including 0.9522 and 1.58. In the crude or adjusted models, individuals with a CMI level ≥ 0.9522 exhibited remarkably increased risk for developing depression. CMI got an AUC of 0.748 in identifying depression. Subgroup analyses and interaction tests indicate that the association between CMI and depression remained consistent across different subgroups and was not modified by other covariates except drinking. Those who are current drinkers and with a high CMI are more susceptible to suffer depression. CONCLUSIONS: An elevated CMI is linked to increased risk for depression. Addressing dyslipidemia and improving lipid levels may potentially lower the risk for depression.