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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Identification of potent and reversible piperidine carboxamides that are species-selective orally active proteasome inhibitors to treat malaria.

Malaria remains a global health concern as drug resistance threatens treatment programs. We identified a piperidine carboxamide (SW042) with anti-malarial activity by phenotypic screening. Selection of SW042-resistant Plasmodium falciparum (Pf) parasites revealed point mutations in the Pf_proteasome ß5 active-site (Pfß5). A potent analog (SW584) showed efficacy in a mouse model of human malaria after oral dosing. SW584 had a low propensity to generate resistance (minimum inoculum for resistance [MIR] >109) and was synergistic with dihydroartemisinin. Pf_proteasome purification was facilitated by His8-tag introduction onto ß7. Inhibition of Pfß5 correlated with parasite killing, without inhibiting human proteasome isoforms or showing cytotoxicity. The Pf_proteasome_SW584 cryoelectron microscopy (cryo-EM) structure showed that SW584 bound non-covalently distal from the catalytic threonine, in an unexplored pocket at the ß5/ß6/ß3 subunit interface that has species differences between Pf and human proteasomes. Identification of a reversible, species selective, orally active series with low resistance propensity provides a path for drugging this essential target.

Serum matrix metalloproteinase-7 for discriminating biliary atresia: a diagnostic accuracy and validation study.

BACKGROUND: Prompt and precise differential diagnosis of biliary atresia (BA) among cholestatic patients is of great importance. Matrix metalloproteinase-7 (MMP-7) holds great promise as a diagnostic marker for BA. This study aimed to investigate the accuracy of age-specific serum MMP-7 for discriminating BA from other cholestatic pediatric patients. METHODS: This was a single center diagnostic accuracy and validation study including both retrospective and prospective cohorts. Serum MMP-7 concentrations were measured using an ELISA kit, the trajectory of which with age was investigated in a healthy infants cohort aged 0 to 365 days without hepatobiliary diseases (n = 284). Clinical BA diagnosis was based on intraoperative cholangiography and subsequent histological examinations. The diagnostic accuracy of age-specific cutoffs of serum MMP-7 were assessed in a retrospective cohort of cholestatic patients (n = 318, with 172 BA) and validated in a prospective cohort (n = 687, including 395 BA). RESULTS: The MMP-7 concentration declines non-linearly with age, showing higher levels in healthy neonates as well as higher cutoff value in neonatal cholestasis. The area under the ROC curve (AUROC) was 0.967 (95% confidence interval [CI]: 0.946-0.988) for the retrospective cohort, and the cutoff of 18 ng/mL yielded 93.0% (95%CI: 88.1-96.3%), 93.8% (95%CI: 88.6-97.1%), 94.7% (95%CI: 90.1-97.5%), and 91.9% (95%CI: 86.4-95.8%) for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), respectively. The performance of MMP-7 was successfully validated in the larger prospective cohort, resulting in a diagnostic sensitivity of 95.9% (379/395; 95% CI: 93.5-97.7%), a specificity of 87.3% (255/292; 95% CI: 83.0-90.9%), a PPV of 91.1% (379/416; 95% CI: 87.9-93.7%), and a NPV of 94.1% (255/271; 95% CI: 90.6-96.6%), respectively. Besides, higher cutoff value of 28.1 ng/mL achieved the best sensitivity, specificity, PPV, and NPV for infants aged 0-30 days, which was 86.4% (95% CI: 75.0-94.0%), 95.5% (95% CI: 77.2-99.9%), 98.1% (95% CI: 89.7-100%), and 72.4% (95% CI: 52.8-87.3%), respectively. CONCLUSIONS: The serum MMP-7 is accurate and reliable in differentiating BA from non-BA cholestasis, showing its potential application in the diagnostic algorithm for BA and significant role in the future research regarding pathogenesis of BA.

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.

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.

Noninvasive cardiac hemodynamics monitoring of acute myocardial ischemia in rats using near-infrared spectroscopy: A pilot study.

Noninvasive and real-time optical detection of cardiac hemodynamics dysfunction during myocardial ischemia remains challenging. In this study, we developed a near-infrared spectroscopy device to monitor rats' myocardial hemodynamics. The well-designed system can accurately reflect the hemodynamics changes by the classic upper limb ischemia test. Systemic hypoxia by disconnecting to the ventilator and cardiac ischemia by coronary artery slipknot ligation was conducted to monitor myocardial hemodynamics. When systemic hypoxia occurred, ΔHbR and ΔtHb increased significantly, whereas ΔHbO decreased rapidly. When coronary blood flow was obstructed by slipknots, cardiothoracic ΔHbO immediately begins to decline, while ΔHbR also significantly increases. Simultaneously, SpO2 did not show any obvious changes during myocardial ischemia, while SpO2 decreased significantly during systemic hypoxia. These results demonstrated that cardiothoracic hemodynamics stemmed from myocardial ischemia. This pilot study demonstrated the practicality of noninvasive, low-cost optical monitoring for cardiac oxygenation dysfunction in rats.

Interface Engineering Induced Multi-Scale Self-Assembly NiFe-LDH Heterostructures for High-Performance Water Electrolysis.

Confronted with the pressing issue of energy scarcity, the development of an economical and potent bifunctional catalyst is of paramount importance. We adopt an interface engineering strategy to modify the surface of NiFe-LDH nanoplates with O2 plasma treatment. This process enhances the local electric field of NiFe-LDH, resulting in the formation of a self-assembled polycrystalline nanowire array on the nanoplate surface. After O2 plasma treatment for 30 min, the NiFe-LDH-P30 not only formed a heterostructure with rough surface, but also regulated the exposure of crystal surfaces. Due to the strong interface coupling between the self-assembled 3D nanoflowers, 2D nanoplates and 1D nanowires, the NiFe-LDH-P30 exhibits an excellent structural stability. Moreover, it demonstrated exceptional HER and OER activities in alkaline condition, achieving a low overpotentials of 154 mV and 242 mV at 10 mA cm-2, respectively. Furthermore, NiFe-LDH-P30 as the dual-electrode material for the cathode and anode in the process of water splitting results in a low voltage of 1.63 V at a current density of 10 mA cm-2. Through the strategic application of interface engineering, this work has pioneered a novel approach to the creation of transition metal-based electrocatalysts, which is benefit to a range of practical energy applications.

Advancing Force Fields Parameterization: A Directed Graph Attention Networks Approach.

Force fields (FFs) are an established tool for simulating large and complex molecular systems. However, parametrizing FFs is a challenging and time-consuming task that relies on empirical heuristics, experimental data, and computational data. Recent efforts aim to automate the assignment of FF parameters using pre-existing databases and on-the-fly ab initio data. In this study, we propose a graph-based force field (GB-FFs) model to directly derive parameters for the Generalized Amber Force Field (GAFF) from chemical environments and research into the influence of functional forms. Our end-to-end parametrization approach predicts parameters by aggregating the basic information in directed molecular graphs, eliminating the need for expert-defined procedures and enhances the accuracy and transferability of GAFF across a broader range of molecular complexes. Simulation results are compared to the original GAFF parametrization. In practice, our results demonstrate an improved transferability of the model, showcasing its improved accuracy in modeling intermolecular and torsional interactions, as well as improved solvation free energies. The optimization approach developed in this work is fully applicable to other nonpolarizable FFs as well as to polarizable ones.

The association between socioeconomic status perception and mental health among Chinese older adults: the mediating roles of social trust and justice.

BACKGROUND: Mental health is a matter of quality of life among older adults. This study aimed to explore the association between the socioeconomic status (SES) perception and mental health of older adults using data from 2017 Chinese General Social Survey (CGSS). METHODS: Ordinary least squares (OLS) regression was used to analyse the association between SES perception and mental health, and the substitution model and variable methods were used to check the robustness of the results. Moreover, we adopted the Sobel model to analyse the mediating roles of social trust and justice. RESULTS: SES perception was positively associated with mental health, and this association was mediated by social trust and justice. This kind of positive association was mainly embodied in those groups with the highest or lowest objective SES. In other words, this study confirmed the phenomenon of "a contented mind is a perpetual feast" in Chinese society. CONCLUSIONS: Higher SES perception is associated with improved mental health for Chinese older adults. It is imperative to prioritize efforts to enhance the perceptual abilities of older adults, particularly those with the highest or lowest objective SES, to promote their overall subjective well-being.

High-Performance Bioinspired Hierarchical Microgroove Wick for Ceramic Vapor Chambers Achieved by Nanosecond Pulsed Lasers.

Directly integrating ceramic vapor chambers into the insulating substrate of semiconductor power devices is an effective approach to solve the problem of heat dissipation. Microgrooves that could be machined directly on the shell plate without contact thermal resistance and mechanical dislocation offer exciting opportunities to achieve high-performance ceramic vapor chambers. In this study, a bioinspired hierarchical microgroove wick (BHMW) containing low ribs via one-step nanosecond pulsed laser processing was developed, as inspired by the Sarracenia trichome. The superwicking behavior of microgrooves with different structural parameters was investigated using capillary rise tests and droplet-spreading experiments. The BHMW exhibited excellent capillary performance and anisotropic hemiwicking performance. At a laser scanning spacing of 30 µm, the BHMW achieved a capillary wicking height of 114 mm within 20 s. The optimized BHMW demonstrated a capillary parameter (ΔPc·K) and an anisotropic hemiwicking ratio of 4.46 × 10-7 N and 11.93, respectively, which were 1182 and 946% higher than references, as achieved through nanosecond pulsed laser texturing under identical parameters. This work not only develops a high-performance hierarchical alumina microgroove wick structure but also outlines design guidelines for high-performance ceramic vapor chambers for thermal management in semiconductor power devices.