Characteristic changes in astrocyte properties during astrocyte-to-neuron conversion induced by NeuroD1/Ascl1/Dlx2.

JOURNAL/nrgr/04.03/01300535-202506000-00030/figure1/v/2024-08-05T133530Z/r/image-tiff Direct in vivo conversion of astrocytes into functional new neurons induced by neural transcription factors has been recognized as a potential new therapeutic intervention for neural injury and degenerative disorders. However, a few recent studies have claimed that neural transcription factors cannot convert astrocytes into neurons, attributing the converted neurons to pre-existing neurons mis-expressing transgenes. In this study, we overexpressed three distinct neural transcription factors--NeuroD1, Ascl1, and Dlx2--in reactive astrocytes in mouse cortices subjected to stab injury, resulting in a series of significant changes in astrocyte properties. Initially, the three neural transcription factors were exclusively expressed in the nuclei of astrocytes. Over time, however, these astrocytes gradually adopted neuronal morphology, and the neural transcription factors was gradually observed in the nuclei of neuron-like cells instead of astrocytes. Furthermore, we noted that transcription factor-infected astrocytes showed a progressive decrease in the expression of astrocytic markers AQP4 (astrocyte endfeet signal), CX43 (gap junction signal), and S100ß. Importantly, none of these changes could be attributed to transgene leakage into pre-existing neurons. Therefore, our findings suggest that neural transcription factors such as NeuroD1, Ascl1, and Dlx2 can effectively convert reactive astrocytes into neurons in the adult mammalian brain.

Zotarolimus alleviates post-trabeculectomy fibrosis via dual functions of anti-inflammation and regulating AMPK/mTOR axis.

OBJECTIVE: Postoperative scar formation is the primary cause of uncontrolled intraocular pressure following trabeculectomy failure. This study aimed to evaluate the efficacy of zotarolimus as an adjuvant anti-scarring agent in the experimental trabeculectomy. METHODS: We performed differential gene and Gene Ontology enrichment analysis on rabbit follicular transcriptome sequencing data (GSE156781). New Zealand white Rabbits were randomly assigned into three groups: Surgery only, Surgery with mitomycin-C treatment, Surgery with zotarolimus treatment. Rabbits were euthanized 3 days or 28 days post-trabeculectomy. Pathological sections were analyzed using immunohistochemistry, immunofluorescence, and Masson staining. In vitro, primary human tenon's capsule fibroblasts (HTFs) were stimulated by transforming growth factor-ß1 (TGF-ß1) and treated with either mitomycin-C or zotarolimus. Cell proliferation and migration were evaluated using cell counting kit-8, cell cycle, and scratch assays. Mitochondrial membrane potential was detected with the JC-1 probe, and reactive oxygen species were detected using the DCFH-DA probe. RNA and protein expressions were quantified using RT-qPCR and immunofluorescence. RESULTS: Transcriptome sequencing analysis revealed the involvement of complex immune factors and metabolic disorders in trabeculectomy outcomes. Zotarolimus effectively inhibited fibrosis, reduced proinflammatory factor release and immune cell infiltration, and improved the surgical outcomes of trabeculectomy. In TGF-ß1-induced HTFs, zotarolimus reduced fibrosis, proliferation, and migration without cytotoxicity via the dual regulation of the TGF-ß1/Smad2/3 and AMPK/AKT/mTOR pathways. CONCLUSION: Our study demonstrates that zotarolimus mitigates fibrosis by reducing immune infiltration and correcting metabolic imbalances, offering a potential treatment for improving trabeculectomy surgical outcomes.

Novel Guanidinium-Functionalized Stigmasterol for Bile Salt Binding and Serum Cholesterol Reduction: Synthesis, Interaction Mechanisms, and In Vivo Function.

A novel amphiphilic guanidyl-functionalized stigmasterol hydrochloride (GFSH) was designed and synthesized as bile salt sequestrants for cholesterol reduction. GFSH exhibited a considerable in vitro capacity for bile salt binding in gastrointestinal digestion and alleviated hypercholesterolemia in vivo. GFSH spontaneously interacted with sodium cholate via synergistic electrostatic, hydrophobic, and hydrogen-bonding interactions. The effects of GFSH on serum cholesterol reduction in mice fed a high-fat-high-cholesterol diet were explored by measuring the expression of key transcription factors related to bile acid metabolism. GFSH produced a dose-dependent reduction in weight gain, hepatic fat accumulation, and fecal and blood markers. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot analyses demonstrated GFSH-induced expression of hepatic CYP7A, LXRα, and LDL-R. GFSH exerts the cholesterol-lowering activity by inducing the bile acid metabolism.

Single-cell sequencing of the vermiform appendix during development identifies transcriptional relationships with appendicitis in preschool children.

BACKGROUND: The development of the human vermiform appendix at the cellular level, as well as its function, is not well understood. Appendicitis in preschool children, although uncommon, is associated with a high perforation rate and increased morbidity. METHODS: We performed single-cell RNA sequencing (scRNA-seq) on the human appendix during fetal and pediatric stages as well as preschool-age inflammatory appendices. Transcriptional features of each cell compartment were discussed in the developing appendix. Cellular interactions and differentiation trajectories were also investigated. We compared scRNA-seq profiles from preschool appendicitis to those of matched healthy controls to reveal disease-associated changes. Bulk transcriptomic data, immunohistochemistry, and real-time quantitative PCR were used to validate the findings. RESULTS: Our analysis identified 76 cell types in total and described the cellular atlas of the developing appendix. We discovered the potential role of the BMP signaling pathway in appendiceal epithelium development and identified HOXC8 and PITX2 as the specific regulons of appendix goblet cells. Higher pericyte coverage, endothelial angiogenesis, and goblet mucus scores together with lower epithelial and endothelial tight junction scores were found in the preschool appendix, which possibly contribute to the clinical features of preschool appendicitis. Preschool appendicitis scRNA-seq profiles revealed that the interleukin-17 signaling pathway may participate in the inflammation process. CONCLUSIONS: Our study provides new insights into the development of the appendix and deepens the understanding of appendicitis in preschool children.

Incidence and outcome of biliary atresia in Shanghai, China from 2015 to 2016: a cohort study.

Demographic characteristics and clinical data of all newly diagnosed biliary atresia patients in Shanghai were collected from 1 January 2015 to 31 October 2016. The total number of live births was 377 420 during the study period, and the incidence of biliary atresia in Shanghai was 10.86 per 100 000 (95% CI 7.8 to 17.74), with 62.9% and 45.7% cases retaining native liver survival at 2 and 5 years after Kasai procedure, respectively. Implementation of systematic screening measures for biliary atresia in China is needed.

Binaphthyl-based chiral covalent organic frameworks for chiral drug separation.

Separation of racemic drugs is of great importance and interest in chemistry and pharmacology. Here, we report the bottom-up synthesis of the binaphthyl-based chiral covalent organic frameworks (CCOFs), (R)-BHTP-COF. Then, high-performance liquid chromatography (HPLC) columns were prepared using (R)-BHTP-COF as a chiral stationary phase (CSP). Racemic ibuprofen was successfully baseline-separated on (R)-BHTP-COF-based CSP, and achieved excellent selectivity (α = 2.32) and chromatographic resolution (Rs = 3.39) factors. Meanwhile, the separation of six racemic drugs by the (R)-BHTP-COF-packed column exhibited high resolution, selectivity, and durability. The successful applications indicate the great potential of CCOFs as a novel stationary phase for efficient HPLC separation.

[Preparation, characterization and antitumor effect of iron-based organic framework nano preparations loaded with piperlongumine].

The preparation processes of iron-based organic framework(FeMOF) MIL-100(Fe) and MIL-101(Fe) with two different ligands were optimized and screened, and the optimized FeMOF was loaded with piperlongumine(PL) to enhance the biocompatibility and antitumor efficacy of PL. The MIL-100(Fe) and MIL-101(Fe) were prepared by solvent thermal method using the optimized reaction solvent. With particle size, polymer dispersity index(PDI), and yield as indexes, the optimal preparation processes of the two were obtained by using the definitive screening design(DSD) experiment and establishing a mathematical model, combined with the Derringer expectation function. After characterization, the best FeMOF was selected to load PL by solvent diffusion method, and the process of loading PL was optimized by a single factor combined with an orthogonal experiment. The CCK-8 method was used to preliminarily evaluate the biological safety of blank FeMOF and the antitumor effect of the drug-loaded nano preparations. The experimental results showed that the optimal preparation process of MIL-100(Fe) was as follows: temperature at 127.8 ℃, reaction time of 14.796 h, total solvent volume of 11.157 mL, and feed ratio of 1.365. The particle size of obtained MIL-100(Fe) nanoparticles was(108.84±2.79)nm; PDI was 0.100±0.023, and yield was 36.93%±0.79%. The optimal preparation process of MIL-101(Fe) was as follows: temperature at 128.1 ℃, reaction time of 6 h, total solvent volume of 10.005 mL, and feed ratio of 0.500. The particle size of obtained MIL-101(Fe) nanoparticles was(254.04±22.03)nm; PDI was 0.289±0.052, and yield was 44.95%±0.45%. The optimal loading process of MIL-100(Fe) loaded with PL was as follows: the feed ratio of MIL-100(Fe) to PL was 1∶2; the concentration of PL solution was 7 mg·mL~(-1), and the ratio of DMF to water was 1∶5. The drug loading capacity of obtained MIL-100(Fe)/PL nanoparticles was 68.86%±1.82%; MIL-100(Fe) was nontoxic to HepG2 cells at a dose of 0-120 µg·mL~(-1), and the half-inhibitory concentration(IC_(50)) of free PL for 24 h treatment of HepG2 cells was 1.542 µg·mL~(-1). The IC_(50) value of MIL-100(Fe)/PL was 1.092 µg·mL~(-1)(measured by PL). In this study, the optimal synthesis process of MIL-100(Fe) and MIL-101(Fe) was optimized by innovatively using the DSD to construct a mathematical model combined with the Derringer expectation function. The optimized preparation process of MIL-100(Fe) nanoparticles and the PL loading process were stable and feasible. The size and shape of MIL-100(Fe) particles were uniform, and the crystal shape was good, with a high drug loading capacity, which could significantly enhance the antitumor effect of PL. This study provides a new method for the optimization of the nano preparation process and lays a foundation for the further development and research of antitumor nano preparations of PL.

Vasorin (VASN) overexpression promotes pulmonary metastasis and resistance to adjuvant chemotherapy in patients with locally advanced rectal cancer.

BACKGROUND: LARC patients commonly receive adjuvant therapy, however, hidden micrometastases still limit the improvement of OS. This study aims to investigate the impact of VASN in rectal cancer with pulmonary metastasis and understand the underlying molecular mechanisms to guide adjuvant chemotherapy selection. METHODS: Sequencing data from rectal cancer patients with pulmonary metastasis from Sun Yat-sen University Cancer Center (SYSUCC) and publicly available data were meticulously analyzed. The functional role of VASN in pulmonary metastasis was validated in vivo and in vitro. Coimmunoprecipitation (co-IP), immunofluorescence, and rescue experiments were conducted to unravel potential molecular mechanisms of VASN. Moreover, VASN expression levels in tumor samples were examined and analyzed for their correlations with pulmonary metastasis status, tumor stage, adjuvant chemotherapy benefit, and survival outcome. RESULTS: Our study revealed a significant association between high VASN expression and pulmonary metastasis in LARC patients. Experiments in vitro and in vivo demonstrated that VASN could promote the cell proliferation, metastasis, and drug resistance of colorectal cancer. Mechanistically, VASN interacts with the NOTCH1 protein, leading to concurrent activation of the NOTCH and MAPK pathways. Clinically, pulmonary metastasis and advanced tumor stage were observed in 90% of VASN-positive patients and 53.5% of VASN-high patients, respectively, and VASN-high patients had a lower five-year survival rate than VASN-low patients (26.7% vs. 83.7%). Moreover, the Cox analysis and OS analysis indicated that VASN was an independent prognostic factor for OS (HR = 7.4, P value < 0.001) and a predictor of adjuvant therapy efficacy in rectal cancer. CONCLUSIONS: Our study highlights the role of VASN in decreasing drug sensitivity and activating the NOTCH and MAPK pathways, which leads to tumorigenesis and pulmonary metastasis. Both experimental and clinical data support that rectal cancer patients with VASN overexpression detected in biopsies have a higher risk of pulmonary metastasis and adjuvant chemotherapy resistance.

Combinatorial control of Pseudomonas aeruginosa biofilm development by quorum-sensing and nutrient-sensing regulators.

The human pathogen Pseudomonas aeruginosa, a leading cause of hospital-acquired infections, inhabits and forms sessile antibiotic-resistant communities called biofilms in a wide range of biotic and abiotic environments. In this study, we examined how two global sensory signaling pathways-the RhlR quorum-sensing system and the CbrA/CbrB nutritional adaptation system-intersect to control biofilm development. Previous work has shown that individually these two systems repress biofilm formation. Here, we used biofilm analyses, RNA-seq, and reporter assays to explore the combined effect of information flow through RhlR and CbrA on biofilm development. We find that the ΔrhlRΔcbrA double mutant exhibits a biofilm morphology and an associated transcriptional response distinct from wildtype and the parent ΔrhlR and ΔcbrA mutants indicating codominance of each signaling pathway. The ΔrhlRΔcbrA mutant gains suppressor mutations that allow biofilm expansion; these mutations map to the crc gene resulting in loss of function of the carbon catabolite repression protein Crc. Furthermore, the combined absence of RhlR and CbrA leads to a drastic reduction in the abundance of the Crc antagonist small RNA CrcZ. Thus, CrcZ acts as the molecular convergence point for quorum- and nutrient-sensing cues. We find that in the absence of antagonism by CrcZ, Crc promotes the expression of biofilm matrix components-Pel exopolysaccharide, and CupB and CupC fimbriae. Therefore, this study uncovers a regulatory link between nutritional adaption and quorum sensing with potential implications for anti-biofilm targeting strategies.IMPORTANCEBacteria often form multicellular communities encased in an extracytoplasmic matrix called biofilms. Biofilm development is controlled by various environmental stimuli that are decoded and converted into appropriate cellular responses. To understand how information from two distinct stimuli is integrated, we used biofilm formation in the human pathogen Pseudomonas aeruginosa as a model and studied the intersection of two global sensory signaling pathways-quorum sensing and nutritional adaptation. Global transcriptomics on biofilm cells and reporter assays suggest parallel regulation of biofilms by each pathway that converges on the abundance of a small RNA antagonist of the carbon catabolite repression protein, Crc. We find a new role of Crc as it modulates the expression of biofilm matrix components in response to the environment. These results expand our understanding of the genetic regulatory strategies that allow P. aeruginosa to successfully develop biofilm communities.

Atorvastatin inhibits Lipopolysaccharide (LPS)-induced vascular inflammation to protect endothelium by inducing Heme Oxygenase-1 (HO-1) expression.

PURPOSE: This study aimed to explore the differential effects of varying doses of atorvastatin on antagonizing lipopolysaccharide (LPS)-induced endothelial inflammation based on heme oxygenase 1 (HO-1) expression. METHOD: Vascular endothelial inflammatory injury was induced in 40 Sprague-Dawley rats by intraperitoneal injection of LPS. These rats were randomly divided into control, low-dose atorvastatin, high-dose atorvastatin, and HO-1 blocking groups. Seven days after treatment, all rats were sacrificed, and heart-derived peripheral blood was collected to measure the serum concentrations of bilirubin, alanine aminotransferase (ALT), total cholesterol, malondialdehyde, endothelial cell protein C receptor, endothelin-1, von Willebrand factor, and soluble thrombomodulin. Meanwhile, the number of circulating endothelial cells was determined using flow cytometry. Vascular tissues from descending aorta of rats from each group were extracted to detect the expression level of HO-1. RESULTS: After different doses of atorvastatin intervention, the above inflammatory indices were decreased, and HO-1 expression and ALT concentration were increased in the atorvastatin-treated group of rats compared with the control group. These changes were more pronounced in the high-dose statin group (P < 0.05). Conversely, no significant decrease in the above inflammatory indices and no significant increase in HO-1 expression were observed in rats in the blocking group (P > 0.05). CONCLUSION: For LPS-induced vascular inflammation, high-dose atorvastatin exerts potent anti-inflammatory and vascular endothelial protection effects by inducing HO-1 expression.

LncRNA MEG9 Promotes Inflammation and Liver Fibrosis Through S100A9 in Biliary Atresia.

BACKGROUND: The pathogenesis of biliary atresia (BA) remains elusive. We aimed to investigate the role of long noncoding RNA (lncRNA) MEG9 in BA. METHODS: LncRNA microarray was conducted to identify differentially expressed lncRNAs in three BA and three para-hepatoblastoma liver tissues. RT-qPCR validated the results. Human intrahepatic bile duct epithelial cells (HIBECs) were stably transfected with lncRNA MEG9 knockdown/overexpression to investigate its cellular localization and function. RNA sequencing (RNA-seq), differentially expressed genes (DEGs) analysis and gene set enrichment analysis were applied to MEG9-overexpresed HIBECs. RNA pull-down and mass spectrometry explored the interacting protein of MEG9, while clinical information was reviewed. RESULTS: 436 differentially expressed lncRNAs were identified, with MEG9 highly upregulated in BA. RT-qPCR further confirmed MEG9's overexpression in BA and diagnostic potential (AUC = 0.9691). MEG9 was predominantly located in the nucleus and significantly promoted cell proliferation and migration. RNA-seq revealed inflammation- and extracellular matrix-related pathways enriched in MEG9-overexpressing HIBECs, with upregulated cytokine genes like CXCL6 and IL6. MMP-7 and collagen I were also overexpressed. Furthermore, 38 proteins were identified to specifically interact with MEG9, and S100A9 was highly expressed in cell models. S100A9 was also significantly upregulated in BA liver tissue and correlated with MEG9 expression (r = 0.313, p < 0.05), albumin level (r = -0.349, p < 0.05), and platelet level (r = -0.324, p < 0.05). CONCLUSION: MEG9 influences cholangiocyte proliferation, migration, and cytokine production, potentially regulating BA inflammation and fibrosis via S100A9 interaction.

Evaluation of comparative chemical profiling and bioactivities of medicinal and non-medicinal parts of Ampelopsis delavayana.

Ampelopsis delavayana, a distinctive Yi medicine, utilized the roots as an essential medicinal substance for trauma treatment of the "Yunnan Hong Yao". A. delavayana, however, cannot be cultivated artificially presently, and it has been described with a phenomenon of mixed utilization of roots and stems, impeding pharmaceutical quality control. In response to resource scarcity and standardization issues, the research comprehensively compares the material basis and efficacy of medicinal (roots) and non-medicinal (stems) parts by using chemical profiling and pharmacological methodologies. Chemical disparity between two parts was compared by TLC and HPLC. Analgesia and anti-inflammatory capabilities of both parts were comprehensively evaluated through acetic acid writhing test, hot plate test, and xylene-induced mouse ear swelling test. Additionally, all the extracts were evaluated for anti-inflammatory activities by monitoring regulation of the levels of TNF-α, IL-1ß, IL-6, and IgE in ear tissue. Consequently, the findings of TLC and HPLC revealed substantial similarity in the material basis of the medicinal and non-medicinal parts of A. delavayana, and pharmacological activities of anti-inflammatory and analgesic between two parts were consistent. Different extracts remarkably reduced the levels of TNF-α, IL-1ß, IL-6, and IgE, demonstrating no discernible differences. Collectively, the comprehensive exploitation indicated that the medicinal and non-medicinal parts of A. delavayana exhibited identical chemical profiling and bioactivities, providing a theoretical rationale and scientific evidence for using stems as a therapeutic part, thereby holding considerable potential for ameliorating the current status of its medicinal reserves.

Anti-seasonal flooding drives substantial alterations in riparian plant diversity and niche characteristics in a unique hydro-fluctuation zone.

Human-induced disturbances such as dam construction and regulation have led to widespread alterations in hydrological processes and thus substantially influence plant characteristics in the hydro-fluctuation zones (HFZs). To reveal utilization of limited resources and mechanisms of inter-specific competition and species co-existence of plant communities based on niche breadth and overlap under the different HFZs of the Three Gorges Reservoir (TGR) in China, we conducted a field investigation with 368 quadrats on the effects of hydrological alterations on plant diversity and niche characteristics. The results showed anti-seasonal flooding precipitated the gradual disappearance of the original diverse niches, resulting in the reduction of plant species richness and functional diversity and more obvious competition among plant species with similar resource requirements. Annuals, perennials and shrubs accounted for 71.23%, 27.39% and 1.37%, respectively, suggesting that annuals and flood-tolerant riparian herbs were favored under such novel flooding conditions. A consistent increase in species number, Shannon-Wiener diversity index and Simpson dominance index with altitude was inconsistent with hump-shaped diversity-disturbance relationship of the intermediate disturbance hypothesis, while the opposite trend was observed for the Pielou evenness index. This species distribution pattern might be caused by several synergetic attributes (e.g., the submergence depth, plant tolerant capacity to flooding, life form, dispersal mode and inter-specific competition). Vegetation types shifted from xerophytes to mesophytes and eventually to hygrophytes with the increasing flooding time in the HFZs. Hydrological alterations proved to be the paramount driver of vegetation distribution in the different HFZs. The niche analysis provided the first insights on the mechanisms of resource utilization and inter-specific competition, of which annuals could germinate quickly after soil drainage to achieve the greatest competitive advantages and occupy a larger niche space than other plants. Vegetation was still in the early stage of primary succession in the novel riparian forests. Therefore, vegetation restoration strategies should be biased towards herbaceous plants, due to annuals with better environmental adaptability, supplemented by shrubs and small trees. To establish a complete reference system for vegetation restoration, natural vegetation monitory plots in the different succession stages should be established in the different HFZs of the TGR, and their environmental conditions, community structures and inter-specific relationships further analyzed.

Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial.

Neoadjuvant chemoradiotherapy (NACRT) was the standard treatment for patients with locally advanced rectal cancer (LARC) with proficient mismatch repair (pMMR) proteins. In this randomized phase 2 trial (ClinicalTrial.gov: NCT04304209), 134 pMMR LARC patients were randomly (1:1) assigned to receive NACRT or NACRT and the programmed cell death protein 1 (PD-1) antibody sintilimab. As the primary endpoint, the total complete response (CR) rate is 26.9% (18/67, 95% confidence interval [CI] 16.0%-37.8%) and 44.8% (30/67, 95% CI 32.6%-57.0%) in the control and experimental arm, respectively, with significant difference (p = 0.031 for chi-squared test). Response ratio is 1.667 (95% CI 1.035-2.683). Immunohistochemistry shows PD-1 ligand 1 (PD-L1) combined positive score is associated with the synergistic effect. The safety profile is similar between the arms. Adding the PD-1 antibody sintilimab to NACRT significantly increases the CR rate in pMMR LARC, with a manageable safety profile. PD-L1 positivity may help identify patients who might benefit most from the combination therapy.

Detection Method of Stator Coating Quality of Flat Wire Motor Based on Improved YOLOv8s.

The stator of a flat wire motor is the core component of new energy vehicles. However, detecting quality defects in the coating process in real-time is a challenge. Moreover, the number of defects is large, and the pixels of a single defect are very few, which make it difficult to distinguish the defect features and make accurate detection more difficult. To solve this problem, this article proposes the YOLOv8s-DFJA network. The network is based on YOLOv8s, which uses DSFI-HEAD to replace the original detection head, realizing task alignment. It enhances joint features between the classification task and localization task and improves the ability of network detection. The LEFG module replaces the C2f module in the backbone of the YOLOv8s network that reduces the redundant parameters brought by the traditional BottleNeck structure. It also enhances the feature extraction and gradient flow ability to achieve the lightweight of the network. For this research, we produced our own dataset of stator coating quality regarding flat wire motors. Data augmentation technology (Gaussian noise, adjusting brightness, etc.) enriches the dataset, to a certain extent, which improves the robustness and generalization ability of YOLOv8s-DFJA. The experimental results show that in the performance of YOLOv8s-DFJA compared with YOLOv8s, the mAP@.5 index increased by 6.4%, the precision index increased by 1.1%, the recall index increased by 8.1%, the FPS index increased by 9.8FPS/s, and the parameters decreased by 3 Mb. Therefore, YOLOv8s-DFJA can be better realize the fast and accurate detection of the stator coating quality of flat wire motors.

Peripheral Lymphocyte Changes Associate With the Progression of Necrotizing Enterocolitis in Infants.

INTRODUCTION: Immune factors are important antecedents in the pathophysiology of necrotizing enterocolitis (NEC). However, studies on the peripheral blood lymphocyte subsets changes in NEC patients among different Bell stages and in patients requiring surgery are scarce. METHODS: 34 infants with NEC and 33 age-matched controls were included. Peripheral blood was collected within 48 h after NEC diagnosis. Peripheral blood B and T lymphocytes subsets were detected by 12-color flow cytometry. Cell ratios were calculated, and their relationship to disease severity and their roles as indicators for surgery were assessed. RESULTS: NEC patients showed elevated percentages of unSwB cells (CD27+IgD+ unswitched memory/activated B cells)/B cells, SwB cells (CD27+IgD-switched memory B cells)/B cells, CD8+ T (CD3+CD8+ T cells)/T cells, Tem (CD45RA-CCR7-effector memory T cells)/CD4+ T cells, Tem/CD8+ T cells and decreased Bn (CD27-IgD+ naïve B cells)/B cells, CD4+T (CD3+CD4+ T cells)/T cells, CD45RA+ CCR7+ naïve T cells (CD45RA+CCR7+ naïve T cells)/CD8+T cells. Compared to NEC patients at BELL stage I + II, patients at BELL stage III showed increased percentages of SwB cells/B cells, antibody secreting cell (ASC, CD3-CD20-CD27high CD38high ASCs)/B cells and Tem/CD4+ T cells, and decreased percentages of CD45RA+CCR7+ naïve T cells/CD4+ T cells. The Receiver Operating Characteristic Curve analysis showed that the sensitivity of ASC/B cells ratio (0.52%) is 86.67% and the specificity of Tem/CD4+T ratio (5.22%) is 100%, indicating that NEC patients required surgery. CONCLUSIONS: The severity of NEC exhibits codirectional changes with the maturation of B and T lymphocytes, especially CD4+ T cells. The increased ASC/B and Tem/CD4+ T cells could serve as potential indicators for NEC patients requiring surgery.

Body Mass and Foot-dominance Disparities in the Foot Plantar Pressure Parameters of Older Women.

OBJECTIVES: To examine the effects of foot dominance and body mass on foot plantar pressures in older women of regular, overweight, and obese weights. METHODS: 96 female adults were divided into regular-weight group (68.30 ± 4.19 yr), overweight group (69.88 ± 3.76 yr), and obesity group (68.47 ± 3.67 yr) based on their body mass index scores. Footscan® plantar pressure test system was used to assess the dynamic plantar pressures, and parameters were collected from risk analysis, foot axis analysis, single foot timing analysis, and pressure analysis. RESULTS: (1) The local risks of lateral forefoot and midfoot, the minimum and maximum subtalar joint angles, the flexibility of subtalar joint, foot flat phase, as well as the average pressures on toes, metatarsals,, midfoot, and lateral heel, with the peak pressures on toe 2-5, metatarsal 2, metatarsal 5, midfoot, and lateral heel had significant within-subject differences. (2) The phases of initial contact and foot flat, the average pressures on toe 2-5, metatarsals, midfoot, and heels, with the peak pressures on metatarsal 1-4, midfoot, and heels exhibited significant between-subjects differences. (3) There was an interaction effect of foot dominance and body mass index on the flexibility of subtalar joint. CONCLUSIONS: The non-dominant foot works better for stability, especially when touching on and off the ground. The dominant foot works better for propulsion but is more susceptible to pain, injury, and falls. For obese older women, the forefoot and midfoot are primarily responsible for maintaining stability, but the lateral midfoot and hindfoot are more prone to pain and discomfort.

Efficient Dlx2-mediated astrocyte-to-neuron conversion and inhibition of neuroinflammation by NeuroD1.

In vivo astrocyte-to-neuron (AtN) conversion induced by overexpression of neural transcriptional factors has great potential for neural regeneration and repair. Here, we demonstrate that a single neural transcriptional factor, Dlx2, converts mouse striatal astrocytes into neurons in a dose-dependent manner. Lineage-tracing studies in Aldh1l1-CreERT2 mice confirm that Dlx2 can convert striatal astrocytes into DARPP32+ and Ctip2+ medium spiny neurons (MSNs). Time-course studies reveal a gradual conversion from astrocytes to neurons in 1 month, with a distinct intermediate state in between astrocytes and neurons. Interestingly, when Dlx2-infected astrocytes start to lose astrocytic markers, the other local astrocytes proliferate to maintain astrocytic levels in the converted areas. Unexpectedly, although Dlx2 efficiently reprograms astrocytes into neurons in the gray matter striatum, it also induces partial reprogramming of astrocytes in the white matter corpus callosum. Such partial reprogramming of white matter astrocytes is associated with neuroinflammation, which can be suppressed by the addition of NeuroD1. Our results highlight the importance of investigating AtN conversion in both the gray matter and white matter to thoroughly evaluate therapeutic potentials. This study also unveils the critical role of anti-inflammation by NeuroD1 during AtN conversion.

Environmental and Climate Impacts on Physiological Aging: Comprehensive Pathways to Enhanced Age-related Resilience.

This perspective article highlights the pressing necessity to focus on heterogeneity in organ-specific aging, emphasizing the influence of environmental and climate changes, as well as social interactions, on the aging process of individual organs. It explores innovative and integrative strategies tailored to the unique aging mechanisms of different organs, aiming to preserve their biological clocks. By emphasizing the importance of addressing organ-specific vulnerabilities, the article calls for transcending traditional pharmacological treatments and organ transplants. It proposes a comprehensive approach that combines environmental management, social support systems, and advanced technological interventions to improve the well-being and longevity of aging populations.

The Safety and Efficacy of Leo Stents with Coiling or Alone for Anterior Cerebral Artery Aneurysms.

INTRODUCTION: Treatment of anterior cerebral artery (ACA) aneurysms is still not well established. The Leo stent with blood flow direction is a retrievable stent for intracranial aneurysms, whereas it needs to be studied clearly in patients with ACA aneurysms. METHODS: Consecutive patients with ACA aneurysms were retrospectively enrolled in three neurosurgical centers between January 2016 and October 2021. The data on demographics, aneurysm characteristics, symptom resolution, and postoperative course were collected and analyzed. The aneurysm occlusion status was appraised by Raymond-Ray Occlusion Class (RROC). RESULTS: A total of 57 patients with ACA aneurysms were included in our study. Immediate postprocedural angiograms showed that 20 aneurysms (35.1%) were in complete occlusion (RROC 1), 26 aneurysms (45.6%) were in near-complete occlusion (RROC 2), 11 aneurysms (19.3%) were in incomplete occlusion (RROC 3). The angiographic follow-up found that the rate of complete occlusion increased to 57.9%, and near-completion and incomplete occlusion dropped to 29.8% and 12.3%, respectively. The angiographic result of the last follow-up improved significantly (Z=- 2.805, P=0.005). Univariate analysis indicated that distal location of aneurysms (Z=4.538, P=0.033) and ruptured aneurysms (χ2=.6120, P=0.032) were potential risk factors for intra-parent artery narrowing. Furthermore, multivariate logistic regression analysis found that A3 aneurysms (95% CI 1.427~32.744, P=0.016) are the key risk factor for intra-parent artery narrowing. CONCLUSIONS: The Leo stent is safe and effective for aneurysms located in ACA circulations. The overall occlusion degree improved during follow-up. A distal, small artery was the risk factor for intra-parent artery narrowing.