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• Frontal cortex plays an important role in Stroop cognitive control. • Cingulate cortex is activated for the Stroop interference effect. • Left dorsolateral prefrontal cortex is activated for the interference effect. • Left and right inferior frontal gyrus may have different roles in the Stroop task. Age plays a significant role in executive control processes in the Stroop task. This study aims to draw together the Stroop tasks to determine the role of the frontal cortex in cognitive control among healthy young adults using activation likelihood estimation. Forty-six studies were selected according to the fMRI neuroimaging tools, Stroop experimental tasks, young participants' age. The results showed that the contrast of incongruent conditions and congruent conditions revealed 7 significant clusters, including the right cingulate cortex, left dorsolateral prefrontal cortex, bilateral inferior frontal gyrus, right superior frontal gyrus and temporal cortex. In addition, the contrast comparing incongruent conditions with neutral conditions activated a network including the right inferior frontal gyrus, left dorsolateral prefrontal cortex, bilateral medial frontal cortex, left insular cortex and bilateral inferior parietal lobule and precuneus. In this study, we found that the brain areas for executive performance had a higher concordance in the frontal cortex among healthy young adults than temporal-parietal network. [ABSTRACT FROM AUTHOR]

Background: Adult Ewing sarcoma (ES) is a rare disease, the optimal treatment model is unknown. This study aimed to retrospectively analyze treatment-related prognostic factors of nonspinal ES in Chinese adults.Methods: Eighty-one patients treated between January 2005 and December 2017 were included in the present study. Thirty-three (40.7%) presented with metastatic disease at diagnosis. Eight patients were submitted to primary surgery followed by chemotherapy, while 73 patients received chemotherapy before and after surgery and/or local radiotherapy. The chemotherapy regimen included 8-17 cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE) every 3 weeks. Clinical outcomes and safety were analyzed.Results: VDC/IE chemotherapy was well tolerated in adult patients with ES. Multivariate Cox regression analyses revealed that chemotherapy of at least 12 cycles was a favorable independent prognostic factor of event-free survival (hazard ratio, 0.558; 95% confidence interval, 0.323-0.965; P = 0.037) and overall survival (hazard ratio, 0.424; 95% confidence interval, 0.240-0.748; P = 0.003). Similarly, a low frequency of chemotherapy delays was an independent prognostic factor of improved OS (hazard ratio, 0.438; 95% confidence interval, 0.217-0.887; P = 0.022).Conclusion: Our study suggests that adults with ES should be treated with an aggressive multidisciplinary approach, intensive chemotherapy with adequate cycles and appropriate intervals can be recommended in this group. [ABSTRACT FROM AUTHOR]

Congenital human cytomegalovirus (HCMV) infection is a major cause of abnormalities and disorders in the central nervous system (CNS) and/or the peripheral nervous system (PNS). However, the complete pathogenesis of neural differentiation disorders caused by HCMV infection remains to be fully elucidated. Stem cells from human exfoliated deciduous teeth (SHEDs) are mesenchymal stem cells (MSCs) with a high proliferation and neurogenic differentiation capacity. Since SHEDs originate from the neural crest of the early embryonic ectoderm, SHEDs were hypothesized to serve as a promising cell line for investigating the pathogenesis of neural differentiation disorders in the PNS caused by congenital HCMV infection. In this work, SHEDs were demonstrated to be fully permissive to HCMV infection and the virus was able to complete its life cycle in SHEDs. Under neurogenic inductive conditions, HCMV infection of SHEDs caused an abnormal neural morphology. The expression of stem/neural cell markers was also disturbed by HCMV infection. The impairment of neural differentiation was mainly due to a reduction of intracellular cholesterol levels caused by HCMV infection. Sterol regulatory element binding protein-2 (SREBP2) is a critical transcription regulator that guides cholesterol synthesis. HCMV infection was shown to hinder the migration of SREBP2 into nucleus and resulted in perinuclear aggregations of SREBP2 during neural differentiation. Our findings provide new insights into the prevention and treatment of nervous system diseases caused by congenital HCMV infection. [ABSTRACT FROM AUTHOR]

• AD is associated with significant regional increase of tau, microglia activation and GM atrophy. • Spatial distributions of different pathologies were highly overlapping. • GM atrophy mediated the effects of tau and neuroinflammation on cognitive impairments. • Multimodal imaging data fusion between multi-tracer PET and MRI. In addition to beta-amyloid accumulation, misfolded tau and activated microglia are also present in Alzheimer's disease (AD). It is important to study the relationship amongst these pathologies in vivo and their effects on the cognitive deficits for developing effective trails and future therapeutic or preventive strategies for AD. To investigate the relationships amongst different pathologies in AD, in particular how they interact resulting in cognitive impairments, we conducted a study of sixty-six subjects (15 AD, 24 Mild Cognitive Impairment (MCI) and 27 similarly aged healthy controls), who underwent standardised clinical and neuropsychological assessments followed by dynamic PET using [18F]AV1451 (tau) and [11C]PK11195 (activated microglia) and multimodal 3T MRI. MCI patients also underwent [11C]PIB (beta-amyloid) PET. We compared regional PET binding and grey matter atrophy amongst AD, amyloid positive MCI and controls, as well as their spatial distribution across different brain areas. We also applied a mediation analysis to infer the direct and indirect effects of tau, neuroinflammation and grey matter atrophy on cognitive functioning. We found increased [18F]AV1451 and [11C]PK11195 binding as well as grey matter atrophy in AD, with a strong spatial overlap amongst these AD related biomarkers suggesting them interacting with each other. We demonstrated that both tau ([18F]AV1451) and neuroinflammation ([11C]PK11195) have significant effects on cognition however their effects were fully mediated by grey matter atrophy. No mediation effect between tau and neuroinflammation were found with respect to cognition. In conclusion, grey matter atrophy not only spatially overlapped with tau and microglia activity in AD, but also mediate them in affecting cognitive impairments. The mediation analysis enabled data fusion across multiple imaging modalities (PET and MRI) and multiple PET tracers. Our results have significant implications for trials targeting tau and inflammation, and future therapeutic or preventive strategies for AD. [ABSTRACT FROM AUTHOR]

Background: Frontal fibrosis alopecia (FFA) is a primary cicatricial alopecia and has received increasing attention in recent years. However, the pathogenesis of FFA has not been fully elucidated. Methods and results: Herein, we collected the transcriptome data of scalp lesions of seven patients with FFA and seven healthy controls. The differential expression analysis and weighted gene co‐expression network analysis were conducted and we identified 458 differentially expressed genes (DEGs) in two key modules. Later, we performed functional enrichment analysis and functional modules identification, revealing the participation of immune response and fatty acid metabolism. Based on the results, we processed further studies. On the one hand, we analyzed the infiltrating immune cells of FFA through CIBERSORT algorithm, indicating the activation of M1 macrophage and CD8+ T cell. On the other hand, considering lipid metabolism of FFA and oxidative stress of hair follicle cells in alopecia, we explored the potential ferroptosis of FFA. By intersection of DEGs and ferroptosis‐related genes from FerrDb database, 19 genes were identified and their expression was validated in an external dataset containing 36 FFA cases and 12 controls. Then, we used LASSO algorithms to construct a four‐gene diagnostic model, which achieved an AUC of 0.924 in validation dataset. Additionally, the immune cells were found to be related to ferroptosis in FFA. Conclusion: Taken together, this study contributed to reveal the molecular mechanisms of FFA and is expected to inspire future research on treatment. [ABSTRACT FROM AUTHOR]

Several studies have emphasized the role of DNA methylation in vitiligo. However, its profile in human skin of individuals with vitiligo remains unknown. Here, we aimed to study the DNA methylation profile of vitiligo using pairwise comparisons of lesions, peri-lesions, and healthy skin. We investigated DNA methylation levels in six lesional skin, six peri-lesional skin, and eight healthy skin samples using an Illumina 850 K methylation chip. We then integrated DNA methylation data with transcriptome data to identify differentially methylated and expressed genes (DMEGs) and analyzed their functional enrichment. Subsequently, we compared the methylation and transcriptome characteristics of all skin samples, and the related genes were further studied using scRNA-seq data. Finally, validation was performed using an external dataset. We observed more DNA hypomethylated sites in patients with vitiligo. Further integrated analysis identified 264 DMEGs that were mainly functionally enriched in cell division, pigmentation, circadian rhythm, fatty acid metabolism, peroxidase activity, synapse regulation, and extracellular matrix. In addition, in the peri-lesional skin, we found that methylation levels of 102 DMEGs differed prior to changes in their transcription levels and identified 16 key pre-DMEGs (ANLN, CDCA3, CENPA, DEPDC1, ECT2, DEPDC1B, HMMR, KIF18A, KIF18B, TTK, KIF23, DCT, EDNRB, MITF, OCA2, and TYRP1). Single-cell RNA analysis showed that these genes were associated with cycling keratinocytes and melanocytes. Further analysis of cellular communication indicated the involvement of the extracellular matrix. The expression of related genes was verified using an external dataset. To the best of our knowledge, this is the first study to report a comprehensive DNA methylation profile of clinical vitiligo and peri-lesional skin. These findings would contribute to future research on the pathogenesis of vitiligo and potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Cell-based immunotherapy shows the therapeutic potential in sarcomas, in addition to angiogenesis-targeted tyrosine kinase inhibitor (TKI) and immune checkpoint inhibitor (ICI). Multi-antigen stimulated cell therapy-I (MASCT-I) technology is a sequential immune cell therapy for cancer, which composes of multiple antigen-loaded dendritic cell (DC) vaccines followed by the adoptive transfer of anti-tumor effector T-cells. Methods: In this phase 1 study, we assessed MASCT-I plus camrelizumab (an ICI against PD-1) and apatinib (a highly selective TKI targeting VEGFR2) in patients with unresectable recurrent or metastatic bone and soft-tissue sarcoma after at least one line of prior systemic therapy. One MASCT-I course consisted of 3 DC subcutaneous injections, followed by 3 active T cell infusions administered 18–27 days after each DC injection. In schedule-I group, 3 DC injections were administered with a 28-day interval in all courses; in schedule-II group, 3 DC injections were administered with a 7-day interval in the first course and with a 28-day interval thereafter. All patients received intravenous camrelizumab 200 mg every 3 weeks and oral apatinib 250 mg daily. Results: From October 30, 2019, to August 12, 2021, 19 patients were enrolled and randomly assigned to schedule-I group (n = 9) and schedule-II group (n = 10). Of the 19 patients, 11 (57.9%) experienced grade 3 or 4 treatment-related adverse events. No treatment-related deaths occurred. Patients in schedule-II group showed similar objective response rate (ORR) with those in schedule-I group (30.0% versus 33.3%) but had higher disease control rate (DCR; 90.0% versus 44.4%) and longer median progression-free survival (PFS; 7.7 versus 4.0 months). For the 13 patients with soft-tissue sarcomas, the ORR was 30.8%, DCR was 76.9%, and median PFS was 12.9 months; for the 6 patients with osteosarcomas, the ORR was 33.3%, the DCR was 50.0%, and median PFS was 5.7 months. Conclusions: Overall, MASCT-I plus camrelizumab and apatinib was safe and showed encouraging efficacy in advanced bone and soft-tissue sarcoma, and schedule-II administration method was recommended. Trial registration: ClinicalTrials.gov, NCT04074564. [ABSTRACT FROM AUTHOR]

Wnt signaling pathways are transmitted via 10 homologous frizzled receptors (FZD1-10) in humans. Reagents broadly inhibiting Wnt signaling pathways reduce growth and metastasis of many tumors, but their therapeutic development has been hampered by the side effect. Inhibitors targeting specific Wnt-FZD pair(s) enriched in cancer cells may reduce side effect, but the therapeutic effect of narrow-spectrum Wnt-FZD inhibitors remains to be established in vivo. Here, we developed a fragment of C. difficile toxin B (TcdBFBD), which recognizes and inhibits a subclass of FZDs, FZD1/2/7, and examined whether targeting this FZD subgroup may offer therapeutic benefits for treating breast cancer models in mice. Utilizing 2 basal-like and 1 luminal-like breast cancer models, we found that TcdBFBD reduces tumor-initiating cells and attenuates growth of basal-like mammary tumor organoids and xenografted tumors, without damaging Wnt-sensitive tissues such as bones in vivo. Furthermore, FZD1/2/7–positive cells are enriched in chemotherapy-resistant cells in both basal-like and luminal mammary tumors treated with cisplatin, and TcdBFBD synergizes strongly with cisplatin in inhibiting both tumor types. These data demonstrate the therapeutic value of narrow-spectrum Wnt signaling inhibitor in treating breast cancers. Wnt signaling is transmitted via ten homologous Frizzled receptors (FZD1-10) in humans, complicating the therapeutic use of inhibitors due to side-effects. This study shows that a bacterial toxin fragment can be used as a tool to specifically inhibit Wnt signaling mediated by a subset of Frizzed receptors (FZD1, 2, 7), with potential for cancer treatment. [ABSTRACT FROM AUTHOR]

[Display omitted] • First study using ATR-FTIR spectroscopy and chemometrics to determine time since human intracerebral hematoma injury. • Compared fresh and formalin-fixed hematomas, developed a model predicting survival time from fixed sample spectra. • This combo shows potential as an effective way to estimate survival time. In cases of violence, intracerebral hemorrhage (ICH) holds significant research importance in forensic medicine. Accurately determining the time since injury (TSI) helps establish the timeline of the incident, playing a crucial role in reconstructing the sequence of events and uncovering the truth in forensic investigations. In the present study, we employed attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy in conjunction with chemometric methods to comprehensively analyze the spectral changes in the central and peripheral regions of human intracerebral hematomas, involving a total of 200 samples from 59 individuals at various survival durations (0–60 days). Initial principal component analysis (PCA) indicated temporal variations in the composition of hematomas along the second principal component (PC2). Subsequently, spectral data were gathered to construct a robust partial least squares (PLS) regression model with predictive capabilities. The root mean square error of cross-validation (RMSECV) and the root mean square error of prediction (RMSEP), both obtained through a genetic algorithm (GA), were determined to be 9 days (R2 = 0.70) and 10 days (R2 = 0.70), respectively. The model, which integrated a collection of variables with enhanced significance and furnished a plurality of high-quality intervals, manifested a moderate degree of performance augmentation relative to conventional full-spectrum PLS models. The intervals identified through GA demonstrated systematic alterations associated with proteins, phospholipids, cholesterol esters, and carbohydrates within the spectral data. The amide I and II bands, which are indicative of the secondary structure of proteins, were identified as the most significant contributors to the results. Based on the results of our preliminary investigation, the application of rapid and non-invasive ATR-FTIR spectroscopy combined with chemometric analysis appears to present a promising methodology for estimating the age of injuries in forensic investigations. [ABSTRACT FROM AUTHOR]

Background: Microbiome-gut-brain axis may be involved in the progression of age-related cognitive impairment and relevant brain structure changes, but evidence from large human cohorts is lacking. This study was aimed to investigate the associations of gut microbiome with cognitive impairment and brain structure based on multi-omics from three independent populations. Methods: We included 1430 participants from the Guangzhou Nutrition and Health Study (GNHS) with both gut microbiome and cognitive assessment data available as a discovery cohort, of whom 272 individuals provided fecal samples twice before cognitive assessment. We selected 208 individuals with baseline microbiome data for brain magnetic resonance imaging during the follow-up visit. Fecal 16S rRNA and shotgun metagenomic sequencing, targeted serum metabolomics, and cytokine measurements were performed in the GNHS. The validation analyses were conducted in an Alzheimer's disease case–control study (replication study 1, n = 90) and another community-based cohort (replication study 2, n = 1300) with cross-sectional dataset. Results: We found protective associations of specific gut microbial genera (Odoribacter, Butyricimonas, and Bacteroides) with cognitive impairment in both the discovery cohort and the replication study 1. Result of Bacteroides was further validated in the replication study 2. Odoribacter was positively associated with hippocampal volume (β, 0.16; 95% CI 0.06–0.26, P = 0.002), which might be mediated by acetic acids. Increased intra-individual alterations in gut microbial composition were found in participants with cognitive impairment. We also identified several serum metabolites and inflammation-associated metagenomic species and pathways linked to impaired cognition. Conclusions: Our findings reveal that specific gut microbial features are closely associated with cognitive impairment and decreased hippocampal volume, which may play an important role in dementia development. [ABSTRACT FROM AUTHOR]

• The property of actual PVCS is investigated by characterizing the EV charging behaviors and PV power distribution to explore the net power data regularity. The external factors that most correlated with PVCS power variation are captured by interpretable algorithms to guide EV behaviors to maximally utilize renewable energy. • At the software algorithm design stage, the forecasting performance trade-off between algorithm complexity and forecasting accuracy is fully considered for edge computing use. The model complexity is maximumly reduced by covering the entire cycle of forecasting process, including input data pruning, lightweight model training, and hyperparameter optimization. • At the hardware configuration stage, forecasting programming is implemented on Raspberry pi-based edge platform for rapid online training. The forecasting model is tested on various scenarios to verify the algorithm feasibility on the edge device. The PV-assisted charging station (PVCS) aggregates the two key resources of electric vehicle (EV) charging load and photovoltaic (PV) system to maximize operation profit. In order to quantify the PVCS impact to grid and the renewable energy utilization by EV charging load, it is crucial to predict the PVCS net power and capture the most correlated factors for power variation. Given that the PVCS is located near the user side, the forecasting model complexity must be restricted to meet the online training demands on edge computing, apart from ensuring the prediction accuracy. A PVCS net power forecasting approach is proposed by simplifying model complexity from the entire cycle of training process, including the input data pruning, lightweight model training and hyperparameter optimization. Finally, a comprehensive analysis of the real data in PVCS shows that the most sensitivity factors affecting the net power of PVCS is time of use price, and the deep auto-encoded extreme learning machine (DA-ELM) can make a satisfactory compromise between prediction accuracy and model complexity for edge computing utilization. The forecasting model has outstanding prediction performance on Raspberry pi-based edge platform, which has enough significance for PVCS promotion. [ABSTRACT FROM AUTHOR]

• The collaborative optimization framework of distribution network and mobile network is proposed. • Optimal models of DNO and MNO with coupon incentive-based DR are established. • Stackelberg game model is employed to model the interaction between DNO and MNO. • Decentralized solution algorithm is designed to obtain SE with limited information exchange. Renewable energy sources are beneficial for both distribution network and mobile network in the context of Smart Grid, but brings greater challenges with high proportions of renewable energy penetration. In this regard, a Stackelberg game-based collaborative optimization approach is proposed for distribution network and 5G mobile network based on demand response, where the distribution network operator (DNO) works as a leader who chooses proper interactive price to reduce the peak-valley difference of net load while mobile network operator (MNO) serves as a follower who minimizes its total energy cost in response to the interactive price set by DNO. Besides, an exact convex relaxation method is proposed to omit the complementarity constraint in the optimal model of MNO, which makes the model strictly convex. Then, the existence and uniqueness of the Stackelberg equilibrium (SE) are analyzed and a distributed solution algorithm is suggested to reach the SE. The simulation results demonstrate that the proposed collaborative optimization approach can not only reduce the cost of DNO and MNO, but helpful to enhance renewable energy utilization, which realizes a win–win result. [ABSTRACT FROM AUTHOR]

[Display omitted] • Sequential degradation and efficient mineralization of TBBPA were achieved in SROS. • SROS produced more ROSs during the oxidation phase. • Degradation pathways of TBBPA in SROS were proposed. • SROS can effectively reduce the toxicity of degradation intermediates of TBBPA. Tetrabromobisphenol A (TBBPA), a brominated flame retardant with environmental hazards poses challenges for degradation into less dangerous small molecule compounds using conventional single reduction or oxidation methods. In this study, N-doped Fe/Fe 3 C@NC was prepared as an efficient catalyst for TBBPA degradation in a sequential reduction–oxidation system (SROS). Nitrogen-doped carbon as support decelerated the oxidation of Fe0 and simultaneously accelerated electron transfer within the composites. After the reduction reaction, the Fe species in Fe/Fe 3 C@NC were converted to Fe2+, which activated peroxymonosulfate more efficiently. Thus, the degradation rate constant (k obs) of TBBPA reached 0.132 min−1, significantly higher than that of a single oxidation system (0.0464 min−1). In addition, the SROS generated more reactive oxygen species, especially O 2 •- and 1O 2 , which facilitated electron transport and consequently led to the rapid degradation of TBBPA. Degradation pathways of TBBPA in a SROS were initially proposed, with TBBPA being debrominated gradually during reduction and then directly oxidized by cleaving the central carbon. TBBPA mineralization percentage in the SROS reached 86 %, which was the result of the reduction initially increased the oxidizability of the pollutant and ring-opening susceptibility. Predicting the toxicity of the intermediates revealed that the intermediate products generated by the SROS during the TBBPA degradation had lower toxicity. This study provides insights into the efficient mineralization of organic pollutants for the remediation of aquatic environments. [ABSTRACT FROM AUTHOR]

• Combination therapy involving siRNA-HIF-1α and Lenvatinib inhibited tumor growth and prolonged mouse survival. • The strategy not only curtailed cell proliferation and angiogenesis within HCC tissues but also stimulated tumor cell apoptosis. • The treatment enhanced T lymphocyte and M1 macrophage presence in tumors, and increased immune cell ratios in the spleen, strengthening anti-tumor immunity. The treatment of hepatocellular carcinoma (HCC) remains a major challenge in the medical field. Lenvatinib, a multi-target tyrosine kinase inhibitor, has demonstrated anti-HCC effects by targeting and inhibiting pathways such as vascular endothelial growth factor receptor 1–3 (VEGFR1-3). However, the therapeutic efficacy of Lenvatinib is subject to various influences, with the hypoxic microenvironment of the tumor being a pivotal factor. Consequently, altering the hypoxic milieu of the tumor emerges as a viable strategy to augment the efficacy of Lenvatinib. Hypoxia-inducible factor-1α (HIF-1α), synthesized by tumor cells in response to oxygen-deprived conditions, regulates the expression of resistance genes, promotes tumor angiogenesis and cell proliferation, enhances tumor cell invasion, and confers resistance to radiotherapy and chemotherapy. Thus, we constructed a self-designed siRNA targeting HIF-1α to suppress its expression and improve the efficacy of Lenvatinib in treating HCC. The therapeutic efficacy of siRNA-HIF-1α in combination with Lenvatinib on HCC were evaluated through in vivo and in vitro experiments. The results showed that the recombinant Salmonella delivering siRNA-HIF-1α in combination with Lenvatinib effectively inhibited tumor growth and prolonged the survival of tumor-bearing mice. This treatment approach reduced cell proliferation and angiogenesis in HCC tissues while promoting tumor cell apoptosis. Additionally, this combined therapy significantly increased the infiltration of T lymphocytes and M1 macrophages within the tumor microenvironment, as well as elevated the proportion of immune cells in the spleen, thereby potentiating the host's immune response against the tumor. [ABSTRACT FROM AUTHOR]

• A RIES energy network modeling and operation problem is studied. • An operation optimization model considering ladder environmental trading is established. • The optimization of the energy network is studied by optimizing the EH in the system. • The economic and environmental benefits of the system could be realized. The energy network is a hub center connecting the energy supply side and the energy demand side, which has high flexibility. At the same time, energy hub is the key to coupling different energy networks. Therefore, from the optimization of the output of the energy hub to the optimization of the coordinated operation state of the multi-energy network is the core of the regional integrated energy system operation optimization research. This paper focuses on the operation optimization of regional integrated energy systems based on modeling of Electricity-Thermal-Natural Gas Network. Firstly, a general model of Electricity network, Natural Gas network, and Thermal network is established, on this basis, according to the coupling mechanism of multi-energy network, a comprehensive model of Electricity-Thermal-Natural Gas coupling system is established. Secondly, considering the constraints such as energy balance and transmission power of external network, an economic dispatching model of regional integrated energy system considering ladder carbon trading mechanism is established with the objective of minimizing economic cost. Thirdly, Fruit Fly Optimization Algorithm is used to solve the economic dispatch model, and the optimization results of the energy hub are obtained. Combined with the general energy network model, the optimization results of each energy network are further obtained according to the characteristics of energy balance and energy flow transmission of the system, including equipment output, gas turbine efficiency, thermal medium velocity, etc. Finally, in order to illustrate the advantages of this method, "Following power load", "Following heat load", and "Optimal scheduling" are set up in the simulation, and the simulation results show that the total operation cost of "Optimal scheduling" mode is reduced by 8.44% and the environmental emission is reduced by 15.03% compared with the other two modes, and the technical and economic characteristics of "Optimal scheduling" mode have strong advantages in the three modes. [ABSTRACT FROM AUTHOR]

Energy management and suitable sizing are regarded as major concerns at the time of designing integrated energy systems. Finding an efficient framework that combines sustainable design, reliable operation and lifetime cost at minimal level is essential for society, customers and investors. In this regard, a novel multi-objective optimization model for the design of integrated energy system with electric, thermal and cooling subsystem is established to simultaneously minimize the economic, technical and environmental objectives. It aims to obtain the optimal sizing of each component such as photovoltaic panels, wind turbine, battery energy storage system, combined cooling, heating and power generation system, heat storage tank, gas boiler and electric chiller considering system performance in economics, system autonomy and carbon emissions. A hybrid energy system in residential area is taken as a case study to demonstrate the application of the proposed method, the Pareto front of the multi-objective problem is obtained via NSGA-II method, and four design plans on the Pareto front selected by Topsis method are analyzed and discussed. Such analysis show that the optimum solution could effectively reduce both the economic and environmental impacts of the integrated energy system as well as improve the system autonomy towards main grid. And the comparison about the results illustrated the reliability of the optimization model in this paper. This study demonstrates the high capability of the proposed design optimization in supporting economic design, improving autonomic operation and reducing the carbon emissions, meanwhile meeting multiple loads. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) is a highly vascularized malignancy that relies on new vessel generation, and thus targeting angiogenesis has been a promising anti-GBM approach. ANGPTL1 is well-known for its anti-angiogenic property; nevertheless, its role in GBM is yet to be explored. Recently, the crucial role of exosomes (Exos) as intercellular communication mediators has gained prominence in GBM therapy. This work aimed to explore the role of exosomal ANGPTL1 in GBM angiogenesis and its mechanisms. Bioinformatic analysis was performed to evaluate ANGPTL expression in GBM. Human GBM cell lines (U87 and U251) and a xenograft mouse model were employed. Exos were isolated from oe-NC- and oe-ANGPTL-transfected bone mesenchymal stem cells and identified. Cell proliferation, migration, and apoptosis were detected. Immunofluorescence, qRT-PCR, western blotting, co-immunoprecipitation, and immunohistochemistry were used to determine the molecular mechanisms underlying exosomal ANGPTL1 against GBM angiogenesis. Besides, tube generation and transmission electron microscope assays were conducted to assess GBM angiogenesis. Low ANGPTL1 expression was observed in GBM tumor tissues and cells. Functionally, e-ANGPTL-Exos inhibited GBM malignant progression and angiogenesis in vitro and in vivo. Mechanically, e-ANGPTL-Exos reduced VEGFA expression and blocked the VEGFR2/Akt/eNOS pathway in GBM cells and tumor tissues. Co-immunoprecipitation revealed a link between ANGPTL1 and VEGFA in GBM cells. Notably, oe-VEGFA abolished the suppressive functions of e-ANGPTL-Exos in GBM progression and angiogenesis and the VEGFR2/Akt/eNOS axis. The VEGFR2 inhibitor, vandetanib, eliminated the promotive effects of oe-VEGFA on GBM angiogenesis with suppressed VEGFR2/Akt/eNOS pathway. Exosomal ANGPTL1 suppressed GBM angiogenesis by inhibiting the VEGFA/VEGFR2/Akt/eNOS axis. • ANGPTL1 expression was decreased in GBM tumor tissues and cells. • Exosomal ANGPTL1 inhibited GBM malignant progression and angiogenesis in vitro and in vivo. • Exosomal ANGPTL1 suppressed GBM cell angiogenesis by blocking the VEGFA/VEGFR2/Akt/eNOS axis. [ABSTRACT FROM AUTHOR]

• Endostatin promotes CD8+ T cell infiltration and PD-1 expression and attenuates M2 TAMs infiltration in melanoma tumors. • The pEndostatin-siRNA-PD-1 plasmid promotes apoptosis and inhibits the proliferation of melanoma tumor cells. • The pEndostatin-siRNA-PD-1 plasmid significantly suppresses melanoma tumor progression. • The pEndostatin-siRNA-PD-1 plasmid modulates the infiltration of immune cells in the tumorsand spleen. Melanoma, the most perilous form of skin cancer, is known for its inherent resistance to chemotherapy. Even with advances in tumor immunotherapy, the survival of patients with advanced or recurrent melanomas remains poor. Over time, melanoma tumor cells may produce excessive angiogenic factors, necessitating the use of combinations of angiogenesis inhibitors, including broad-spectrum options, to combat melanoma. Among these inhibitors, Endostatin is one of the most broad-spectrum and least toxic angiogenesis inhibitors. We found Endostatin significantly increased the infiltration of CD8+ T cells and reduced the infiltration of M2 tumor-associated macrophages (TAMs) in the melanoma tumor microenvironment (TME). Interestingly, we also observed high expression levels of programmed death 1 (PD-1), an essential immune checkpoint molecule associated with tumor immune evasion, within the melanoma tumor microenvironment despite the use of Endostatin. To address this issue, we investigated the effects of a plasmid expressing Endostatin and PD-1 siRNA, wherein Endostatin was overexpressed while RNA interference (RNAi) targeted PD-1. These therapeutic agents were delivered using attenuated Salmonella in melanoma-bearing mice. Our results demonstrate that pEndostatin-siRNA-PD-1 therapy exhibits optimal therapeutic efficacy against melanoma. We found that pEndostatin-siRNA-PD-1 therapy promotes the infiltration of CD8+ T cells and the expression of granzyme B in melanoma tumors. Importantly, combined inhibition of angiogenesis and PD-1 significantly suppresses melanoma tumor progression compared with the inhibition of angiogenesis or PD-1 alone. Based on these findings, our study suggests that combining PD-1 inhibition with angiogenesis inhibitors holds promise as a clinical strategy for the treatment of melanoma. [ABSTRACT FROM AUTHOR]

Microcystin-LR (MC-LR) affects bone health in adult mice via osteo-immunomodulation. However, its effect on osteoblasts and bone development is unclear. This study investigated the effect of MC-LR on bone osteoimmune and osteoblasts in the developing period. 18 Four-week-old male Sprague Dawley rats were divided into two groups (n = 9 per group) and exposed to 0 (control) and 1 μg/kg b.w. MC-LR (exposure) by intraperitoneal injection for four weeks. The heart blood was collected for serological examination, and the femur for morphological, histopathological, and biomechanical analysis. MC-LR exposure significantly weakened bone microstructures (bone volume, bone volume/total volume, bone trabecular number, connectivity density) and biomechanics (maximum loads and maximum deflection) (P < 0.05). Besides, MC-LR decreased serum procollagen type І car-boxy-terminal propeptide, osteocalcin, bone morphogenetic protein-2, osteoprotegerin, and receptor activator of nuclear factor κB ligand, while elevating osteoclasts number, matrix metalloproteinase-9, β-catenin, Runt-related transcription factor 2, and osterix in bone, and bone alkaline phosphate, C-terminal cross-linked telopeptide of type-I collagen, tartrate-resistant acid phosphatase-5b in serum (P < 0.05). Moreover, MC-LR increased CD4+ T-cells, CD4+/CD8+, M1 and M2 macrophages, and cells apoptosis in the bone marrow, interleukin-6, interleukin-17, and tumor necrosis factor-α in serum, decreased serum interleukin-10 (P < 0.05). Overall, MC-LR can promote bone resorption by activating osteoclasts via osteoimmunology, which may involve macrophages besides lymphocytes. MC-LR may inhibit bone formation by stopping the osteoblasts at an immature stage. Thus, MC-LR weakened bone microstructure and biomechanics in developing period. Its risk on bone development needs further study. [ABSTRACT FROM AUTHOR]

• A model-free method of permittivity analysis to reveal EMR response of biomaterial. • A featured signal of cells/lipid membranes relevant to β-dispersion is observed. • The results of our method and the model-fitting method are positively correlated. • Our method requires less computing resource and is applicable to other materials. Electromagnetic radiation (EMR) is omnipresent on earth and may interact with the biological systems in diverse manners. But the scope and nature of such interactions remain poorly understood. In this study, we have measured the permittivity of cells and lipid membranes over the EMR frequency range of 20 Hz to 4.35 × 1010 Hz. To identify EMR frequencies that display physically intuitive permittivity features, we have developed a model-free method that relies on a potassium chloride reference solution of direct-current (DC) conductivity equal to that of the target sample. The dielectric constant, which reflects the capacity to store energy, displays a characteristic peak at 105–106 Hz. The dielectric loss factor, which represents EMR absorption, is markedly enhanced at 107–109 Hz. The fine characteristic features are influenced by the size and composition of these membraned structures. Mechanical disruption results in abrogation of these characteristic features. Enhanced energy storage at 105–106 Hz and energy absorption at 107–109 Hz may affect certain membrane activity relevant to cellular function. [ABSTRACT FROM AUTHOR]

Currently, there is great interest in making neuroimaging widely accessible and thus expanding the sampling population for better understanding and preventing diseases. The use of wearable health devices has skyrocketed in recent years, allowing continuous assessment of physiological parameters in patients and research cohorts. While most health wearables monitor the heart, lungs and skeletal muscles, devices targeting the brain are currently lacking. To promote brain health in the general population, we developed a novel, low-cost wireless cerebral oximeter called FlexNIRS. The device has 4 LEDs and 3 photodiode detectors arranged in a symmetric geometry, which allows for a self-calibrated multi-distance method to recover cerebral hemoglobin oxygenation (SO 2) at a rate of 100 Hz. The device is powered by a rechargeable battery and uses Bluetooth Low Energy (BLE) for wireless communication. We developed an Android application for portable data collection and real-time analysis and display. Characterization tests in phantoms and human participants show very low noise (noise-equivalent power <70 fW/√Hz) and robustness of SO 2 quantification in vivo. The estimated cost is on the order of $50/unit for 1000 units, and our goal is to share the device with the research community following an open-source model. The low cost, ease-of-use, smart-phone readiness, accurate SO 2 quantification, real time data quality feedback, and long battery life make prolonged monitoring feasible in low resource settings, including typically medically underserved communities, and enable new community and telehealth applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Combining with the Hidden Markov Model and Bi-directional Maximal Matching algorithm, a new word segmentation algorithm, HMM-BiMM, is presented. In terms of the sub-dictionary matching, it can implement a fast word segmentation. After segmenting the text by the Bi-directional Maximal Matching (BiMM), the remaining text connected by the remaining single words will be segmented again by the strategy of the Hidden Markov Model (HMM). By the HMM, this algorithm can realize the dictionary dynamic update by the new segmentation words and improve the segmentation accuracy accordingly. Compared with five representative algorithms in the real-world clinical text (symptom), we show that the HMM-BiMM algorithm achieves the highest efficiency and accuracy for symptom text segmentation. In detail, this algorithm has around 3% in precision and 70% in running time improved to the BiMM. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) and microcystin-LR (MC-LR) co-existed in food and water, and were associated with hepatocellular carcinoma (HCC). AFB1 induced HCC by activating oxidative stress and generating AFB1-DNA adducts, while MC-LR could promote HCC progression. However, whether they have co-effects in HCC progression remains uncertain. In this study, we found the antagonistic effects of MC-LR on AFB1 induced HCC when they were exposed simultaneously. Compared with single exposure to AFB1, co-exposed to MC-LR significantly repressed the AFB1 induced malignant transformation of human hepatic cells and the glutathione S-transferase Pi positive foci formation in rat livers. MC-LR inhibited AFB1 induced upregulation of cytochrome P450 family 1 subfamily A member 2 (CYP1A2) and reduced the AFB1-DNA adducts generation in both human hepatic cells and rat livers. These results suggest that when co-exposure with AFB1, MC-LR might repress hepatocarcinogenicity of AFB1, which might be associated with its repression on AFB1 induced CYP1A2 upregulation and activation. • AFB1 and MC-LR co-exist in food and water in humid and warm areas. • Co-exposed to MC-LR antagonize hepato-carcinogenicity of AFB1. • MC-LR repress AFB1 induced upregulation and activation of CYP1A2. • MC-LR inhibit the formation of AFB1-DNA adducts. [ABSTRACT FROM AUTHOR]

Electrophysiological recording of neurons in deep brain regions using optogenetic stimulation is a powerful method for understanding and regulating the role of complex neural activity in biological behavior and cognitive function. Optogenetic techniques have significantly advanced neuroscience research by enabling the optical manipulation of neural activities. Because of the significance of the technique, constant advancements in implantable optrodes that integrate optical stimulation with low-noise, large-scale electrophysiological recording are in demand to improve the spatiotemporal resolution for various experimental designs and future clinical applications. However, robust and easy-to-use neural optrodes that integrate neural recording arrays with high-intensity light emitting diodes (LEDs) are still lacking. Here, we propose a neural optrode based on Gallium Nitride (GaN) on sapphire technology, which integrates a high-intensity blue LED with a 5 × 2 recording array monolithically for simultaneous neural recording and optogenetic manipulation. To reduce the noise interference between the recording electrodes and the LED, which is in close physical proximity, three metal grounding interlayers were incorporated within the optrode, and their ability to reduce LED-induced artifacts during neural recording was confirmed through both electromagnetic simulations and experimental demonstrations. The capability of the sapphire optrode to record action potentials has been demonstrated by recording the firing of mitral/tuft cells in the olfactory bulbs of mice in vivo. Additionally, the elevation of action potential firing due to optogenetic stimulation observed using the sapphire probe in medial superior olive (MSO) neurons of the gerbil auditory brainstem confirms the capability of this sapphire optrode to precisely access neural activities in deep brain regions under complex experimental designs.

Microcystin-LR (MC-LR), a prevalent cyanotoxin present in hazardous cyanobacterial blooms, is recognized as a neurotoxic environmental pollutant that induces brain damage and neurobehavioral deficits. However, the mechanisms underlying MC-LR-induced neurotoxicity remain unclear. This study aims to elucidate the role of mitophagy in MC-LR-induced neurotoxicity both in vitro and in vivo. We found that administration of 10 μg/kg body weight (intraperitoneally) MC-LR impaired learning and memory abilities and induced neuronal damage and apoptosis in the CA1 region of the hippocampus in rats. Exposure to MC-LR (1 μM-10 μM) resulted in cellular damage and apoptosis in PC-12 and HT22 cells. MC-LR induced mitophagy through the PINK1/Parkin pathway but hindered mitophagy progression by repressing Scd2 transcription in neurons. These inhibitory effects were reversed by Scd2 overexpression. Furthermore, MC-LR was found to repress Scd2 transcription by directly binding to type 1 insulin-like growth factor receptor (IGF-1R) and competitively inhibiting its activation by Insulin-like growth factor 1 (IGF-1). Overexpression of IGF-1R and administration of exogenous IGF-1 mitigated the MC-LR-induced inhibition of Scd2 and the associated mitophagy defects. These findings indicate that IGF-1R is the direct target of MC-LR in neurons. MC-LR initiates mitophagy defects and apoptosis by inhibiting Scd2 transcription through binding to IGF-1R., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The cleaning of water supply pipelines represents an increasingly prevalent global practice with the aim of providing high-quality drinking water. Ice pigging, a widely-utilized pipe cleaning technique, can effectively remove substantial sediment sediments from pipe walls. During this process, micropollutants adsorbed to the sediments are inevitably released into the effluent, posing a potential threat to public health. Existing technologies can only address these micropollutants through various post-treatment methods. To improve pipeline cleaning efficiency and reduce costs, we have developed an enhanced ice slurry by adding a minute quantity of peroxymonosulfate (PMS) into the base ice slurry for ultrafast, in-situ removal of micropollutants within sediments. Comparative studies with the base ice slurry demonstrate a significant enhancement in the removal efficiency of the common micropollutant carbamazepine (CBZ) using the enhanced ice slurry. While the removal efficiency of CBZ ranged from 16 to 23 % with increasing NaCl content from 3 to 7 wt% over 10 min for the base ice slurry, nearly complete removal of CBZ was achieved within 1 min by introducing 10 μM PMS into the base ice slurry. The influence of operational parameters (e.g., PMS and Cl - concentrations, cleaning flow velocity) and pipeline characteristics (e.g., CBZ and Fe 2+ concentrations, turbidity, pipe sediment) on CBZ removal efficiency was comprehensively examined for the enhanced ice slurry. The enhanced micropollutant removal process was mainly driven by active species such as hydroxyl and sulfate. Remarkably, chlorinated byproducts were scarcely detected during ice pigging, and the degradation products exhibited minimal ecotoxicity. With a cost of 0.16 Euro per cubic meter of cleaned pipe, the enhanced ice slurry presents a notable economic advantage over alternative methods. Overall, the enhanced ice slurry offers an environmentally friendly, cost-effective, and efficient solution for reducing micropollutants in water supply systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)

Abstract: Oxidative stress due to aberrant metabolism is considered as a crucial contributor to diabetes and its complications. Hyperglycemia and hyperlipemia boost excessive reactive oxygen species generation by elevated mitochondrial respiration, increased nicotinamide adenine dinucleotide phosphate oxidase activity, and enhanced pro-oxidative processes, including protein kinase C pathways, hexosamine, polyol, and advanced glycation endproducts, which exacerbate oxidative stress. Oxidative stress plays a significant role in the onset of diabetes and its associated complications by impairing insulin production, increasing insulin resistance, maintaining hyperglycemic memory, and inducing systemic inflammation. A more profound comprehension of the molecular processes that link oxidative stress to diabetes is crucial to new preventive and therapeutic strategies. Therefore, this review discusses the mechanisms underlying how oxidative stress contributes to diabetes mellitus and its complications. We also summarize the current approaches for prevention and treatment by targeting the oxidative stress pathways in diabetes., (Copyright © 2024 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Introduction: This study evaluates the effectiveness of Traditional Chinese Medicine (TCM) extracts in blocking the interaction between the SARS-CoV-2 Spike protein and human ACE2 receptor, utilizing a dual-method approach to explore the antiviral potential of natural compounds., Objectives: This work aims to evaluate the capability of TCM extracts in inhibiting the SARS-CoV-2 Spike protein and ACE2 receptor interaction using advanced biochemical assays., Methods: A dual-method screening approach was utilized, beginning with a pseudovirus assay to assess the inhibition capabilities of TCM extracts in vitro, followed by a split-ubiquitin yeast two-hybrid (Y2H) system to validate interactions in live cells. Active compounds were characterized and quantified using UPLC-Q-Exactive-Orbitrap-MS., Results: Among the 91 TCM extracts tested, Rosmarinus officinalis exhibited the most potent inhibition in both pseudovirus and Y2H assays, significantly reducing viral entry and disrupting the Spike-ACE2 interaction. Comprehensive chemical profiling via UPLC-Q-Exactive-Orbitrap-MS identified 132 compounds, including phenolics, flavonoids, and terpenoids., Conclusion: This research validates the use of TCM extracts in viral inhibition strategies, demonstrating the utility of integrating traditional remedies with modern scientific approaches to discover new therapeutic agents., (© 2024 John Wiley & Sons Ltd.)

Background: Attention deficits are notable in Lewy body dementia (LBD) and in Alzheimer's disease (AD). In this study, we combined functional magnetic resonance imaging (fMRI) and electroencephalograph (EEG) to detect neural correlates of attention dysfunctions in LBD and AD. Methods: We recruited 33 patients with LBD, 15 patients with AD and 19 elderly healthy controls. The participants performed the modified Attention Network Task (ANT) to investigate the attention dysfunctions. Results: We found that LBD had alerting attention deficits and AD showed apparent orienting attention dysfunctions, while LBD and AD maintained relatively normal executive/conflict attention. Based on source-level EEG analyses, LBD had frontal-central deficits for alerting attention while AD showed inferior frontal and precentral impairments for orienting attention. In addition, the insular and inferior frontal areas were hyper-activated in LBD and AD for executive/conflict attention. Apart from these areas, LBD showed activity in the complementary temporal-central-occipital network for the modified ANT task. Furthermore, the oscillational sources for the ANT effects indicated that the alpha and theta bands were partly impaired in dementia patients. Conclusions: In summary, using source-localised EEG, we found that attention dysfunctions in LBD and AD engaged different neural networks.

Chronic heart failure (CHF) is closely associated with inflammation and mitochondrial dysfunction in cardiomyocytes. This study attempts to investigate the effects of microRNA-21-3p (miR-21-3p) on macrophage polarization and mitophagy in CHF. Here we found miR-21-3p was upregulated in CHF and negatively correlated with carnitine palmitoyl transferase 1A (CPT1A). L-palmitoyl carnitine (L-PC) exacerbated isoproterenol (ISO)-induced myocardial structural disruption and fibrosis in rats, which was exacerbated by miR-21-3p. Mechanistically, miR-21-3p accelerated M1 macrophage polarization. Both miR-21-3p inhibitor and CPT1A overexpression suppressed mitophagy. The inhibition of CPT1A on mitophagy was reversed by miR-21-3p. MiR-21-3p targeted CPT1A mRNA and co-localized with CPT1A protein in cardiomyocytes. In the co-culture system of M1 macrophages and H9c2 cells, miR-21-3p mimics in H9c2 cells promoted M1 polarization, whereas miR-21-3p inhibitor reduced M1 phenotype. M1 macrophages exacerbated H9c2 cell damage. These findings support the potential therapeutic targeting of miR-21-3p to regulate inflammation and mitophagy by inducing CPT1A in CHF., (© 2024. The Author(s).)

Purpose: The overall survival rate for metastatic osteosarcoma hovers around 20%. Responses to second-line chemotherapy, targeted therapies, and immunotherapies have demonstrated limited efficacy in metastatic osteosarcoma. Our objective is to validate differentially expressed genes and signaling pathways between non-metastatic and metastatic osteosarcoma, employing single-cell RNA sequencing (scRNA-seq) and additional functional investigations. We aim to enhance comprehension of metastatic mechanisms and potentially unveil a therapeutic target., Methods: scRNA-seq was performed on two primary osteosarcoma lesions (1 non-metastatic and 1 metastatic). Seurat package facilitated dimensionality reduction and cluster identification. Copy number variation (CNV) was predicted using InferCNV. CellChat characterized ligand-receptor-based intercellular communication networks. Differentially expressed genes underwent GO function enrichment analysis and GSEA. Validation was achieved through the GSE152048 dataset, which identified PDGFD-PDGFRB as a common ligand-receptor pair with significant contribution. Immunohistochemistry assessed PDGFD and PDGFRB expression, while multicolor immunofluorescence and flow cytometry provided insight into spatial relationships and the tumor immune microenvironment. Kaplan-Meier survival analysis compared metastasis-free survival and overall survival between high and low levels of PDGFD and PDGFRB. Manipulation of PDGFD expression in primary osteosarcoma cells examined invasion abilities and related markers., Results: Ten clusters encompassing osteoblasts, osteoclasts, osteocytes, fibroblasts, pericytes, endothelial cells, myeloid cells, T cells, B cells, and proliferating cells were identified. Osteoblasts, osteoclasts, and osteocytes exhibited heightened CNV levels. Ligand-receptor-based communication networks exposed significant fibroblast crosstalk with other cell types, and the PDGF signaling pathway was activated in non-metastatic osteosarcoma primary lesion. These results were corroborated by the GSE152048 dataset, confirming the prominence of PDGFD-PDGFRB as a common ligand-receptor pair. Immunohistochemistry demonstrated considerably greater PDGFD expression in non-metastatic osteosarcoma tissues and organoids, correlating with extended metastasis-free and overall survival. PDGFRB expression showed no significant variation between non-metastatic and metastatic osteosarcoma, nor strong correlations with survival times. Multicolor immunofluorescence suggested co-localization of PDGFD with PDGFRB. Flow cytometry unveiled a highly immunosuppressive microenvironment in metastatic osteosarcoma. Manipulating PDGFD expression demonstrated altered invasive abilities and marker expressions in primary osteosarcoma cells from both non-metastatic and metastatic lesions., Conclusions: scRNA-seq illuminated the activation of the PDGF signaling pathway in primary lesion of non-metastatic osteosarcoma. PDGFD displayed an inhibitory effect on osteosarcoma metastasis, likely through the suppression of the EMT signaling pathway., (© 2024. The Author(s).)

Strontium-rich mineral water (strontium > 0.20 mg/L) is the second largest type of mineral water on commercial drinking water market. Exposure to high levels of strontium through drinking water or soil may interfere with calcium metabolism and increase the risk of cardiovascular and skeletal diseases, but no in-depth mechanism has been disclosed to date. Data on liver metabolic alterations in rats resulted from drinking natural high strontium mineral water (strontium 26.06 mg/L, SrHW) or tap water (filtered by activated carbon, strontium 0.49 mg/L, TW) for 3 months were obtained and analyzed with non-targeted metabolomics strategy. Compared with rats drinking TW, those drinking SrHW showed a significant change in 36 liver metabolites. Among them, 33 liver metabolites (including 14 amino acids, 6 carbohydrates, 4 short-chain fatty acids, 4 organic acids, 2 phenylpropanoic acids, 1 fatty acid, 1 peptide, and 1 bile acid) were down-regulated, and 3 (hydroxyphenyllactic acid, propionylcarnitine and S-adenosine homocysteine) were up-regulated. Metabolic pathway analysis showed that aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, and alanine, aspartate and glutamate metabolism are most impacted. Furthermore, the serum prealbumin content also significantly decreased in rats drinking SrHW. Therefore, changes in liver metabolites and serum protein levels suggested that high concentration of strontium in water was associated with decreased liver protein synthesis; changes in liver metabolites suggested that high strontium was associated with decreased lipid levels. In conclusion, high strontium in water may exert a negative effect on protein synthesis, and further study on the dose-response relationship is necessary., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Long noncoding RNA nuclear enriched abundant transcript 1 (NEAT1) has been reported to be involved in depression. This study aims to investigate the mechanism of NEAT1/microRNA (miR)-320-3p/Corticotropin-releasing hormone receptor 1 (CRHR1) axis in depressed rats. Rats with depression-like behaviors were prepared by exposing the rats to chronic unpredictable mild stress. Behavioral functions, pathological damage, neuronal apoptosis and monoamine neurotransmitter were examined in depressed rats . Primary hippocampal neurons were injured through simulation with corticosterone(CORT). Cell viability and apoptosis were measured in CORT-Induced hippocampal neurons. The binding relationship between NEAT1 and miR-320-3p and the targeting relationship between miR-320-3p and CRHR1 were detected. Elevated NEAT1, CRHR1 and reduced miR-320-3p exhibited in depressed rats and CORT-treated hippocampal neurons, NEAT1 bound to miR-320-3p to target CRHR1. Silencing NEAT1 or elevating miR-320-3p improved behavioral functions, attenuated pathological damage and apoptosis in the hippocampus, and increased monoamine neurotransmitter in depressed rats. Repression of NEAT1 or promotion of miR-320-3p enhanced viability and suppressed apoptosis of CORT-treated hippocampal neurons. The study highlights that NEAT1 competitively binds to miR-320-3p to up-regulate CRHR1 expression, thereby promoting hippocampal damage of depressed rats., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study looked at how desalinated seawater, which has low minerals and high boron, could affect bone health. Prior research suggests that low mineral water may harm bone health and boron could be beneficial, but the overall impact on bone health is still unclear. Eighty-nine-week-old male Balb/C mice were allocated into eight groups and administered either tap water or purified water with varying boron concentrations (0, 5, 40, and 200 mg/L). They were kept in an environment mimicking tropical conditions (35-40 °C, 70-80% humidity) and underwent daily treadmill exercise for 13 weeks. At the 14th week, serum, femora, and lumbar vertebrae were collected for mineral metabolism, bone biomarker, microstructure, and biomechanics evaluation. Boron exposure improved bone formation, microstructure, and biomechanics initially but the benefits weakened with higher levels of exposure ( p < 0.05). Co-exposure to purified water elevated serum boron but weakened the promotion of boron on bone minerals and the bone benefits of boron compared to tap water ( p < 0.05). Thus, when studying the health effects of boron in desalinated seawater, it is crucial to look at various health effects beyond bone health. Furthermore, it is important to consider the mineral composition of drinking water when using boron for bone health benefits.

Electrophysiological recordings of neurons in deep brain regions using optogenetic stimulation are essential to understanding and regulating the role of complex neural activity in biological behavior and cognitive function. Optogenetic techniques have significantly advanced neuroscience research by enabling the optical manipulation of neural activities. Because of the significance of the technique, constant advancements in implantable optrodes that integrate optical stimulation with low-noise, large-scale electrophysiological recording are in demand to improve the spatiotemporal resolution for various experimental designs and future clinical applications. However, robust and easy-to-use neural optrodes that integrate neural recording arrays with high-intensity light emitting diodes (LEDs) are still lacking. Here, we propose a neural optrode based on Gallium Nitride (GaN) on sapphire technology, which integrates a high-intensity blue LED with a 5x2 recording array monolithically for simultaneous neural recording and optogenetic manipulation. To reduce the noise interference between the recording electrodes and the LED, which is in close physical proximity, three metal grounding interlayers were incorporated within the optrode, and their ability to reduce LED-induced artifacts during neural recording was confirmed through both electromagnetic simulations and experimental demonstrations. The capability of the sapphire optrode to record action potentials has been demonstrated by recording the firing of mitral/tuft cells in the olfactory bulbs of mice in vivo. Additionally, the elevation of action potential firing due to optogenetic stimulation observed using the sapphire probe in medial superior olive (MSO) neurons of the gerbil auditory brainstem confirms the capability of this sapphire optrode to precisely access neural activities in deep brain regions under complex experimental designs.

Six new phenylpropanoid glycosides ( 1 - 6 ), two new phenylethanol glycosides ( 7 and 8 ), one new phenylmethanol glycoside ( 9 ), three new phenylpropanoid dimers ( 10 - 12 ), two new phenylpropanoid-flavan-3-ol heterodimers ( 13 and 14 ), and six known relevant compounds ( 15 - 20 ) were isolated and identified from the well-liked edible and medicinal substance (the bark of Cinnamomum cassia (L.) J.Presl). The structures of these isolates were determined by using spectroscopic analyses, chemical methods, and quantum chemical calculations. Notably, compounds 4 - 9 were rare apiuronyl-containing glycosides, and compounds 13 and 14 were heterodimers of phenylpropanoids and flavan-3-ols linked through C-9″-C-8 bonds. The antioxidant and α-glucosidase inhibitory activities of all isolates were evaluated. Compounds 10 and 12 exhibited DPPH radical scavenging capacities with IC 50 values of 20.1 and 13.0 μM, respectively (vitamin C IC 50 value of 14.3 μM). In the ORAC experiment, all these compounds exhibited different levels of capacity for scavenging free radicals, and compound 10 displayed extraordinary free radical scavenging capacity with the ORAC value of 6.42 ± 0.01 μM TE/μM (EGCG ORAC value of 1.54 ± 0.02 μM TE/μM). Compound 12 also showed significant α-glucosidase inhibitory activity with an IC 50 of 56.3 μM (acarbose IC 50 of 519.4 μM).

The consumption of low-mineral water has been increasing worldwide. Drinking low-mineral water is associated with cardiovascular disease, osteopenia, and certain neurodegenerative diseases. However, the specific mechanism remains unclear. The liver metabolic alterations in rats induced by drinking purified water for 3 months were investigated with a metabolomics-based strategy. Compared with the tap water group, 74 metabolites were significantly changed in the purified water group (6 increased and 68 decreased), including 29 amino acids, 11 carbohydrates, 10 fatty acids, 7 short chain fatty acids (SCFAs), and 17 other biomolecules. Eight metabolic pathways were significantly changed, namely aminoacyl-tRNA biosynthesis; nitrogen metabolism; alanine, aspartate and glutamate metabolism; arginine and proline metabolism; histidine metabolism; biosynthesis of unsaturated fatty acids; butanoate metabolism; and glycine, serine and threonine metabolism. These changes suggested that consumption of purified water induced negative nitrogen balance, reduced expression of some polyunsaturated fatty acids and SCFAs, and disturbed energy metabolism in rats. These metabolic disturbances may contribute to low-mineral-water-associated health risks. The health risk of consuming low-mineral water requires attention.

The aging brain represents the primary risk factor for many neurodegenerative disorders. Whole-brain oscillations may contribute novel early biomarkers of aging. Here, we investigated the dynamic oscillatory neural activities across lifespan (from 18 to 88 years) using resting Magnetoencephalography (MEG) in a large cohort of 624 individuals. Our aim was to examine the patterns of oscillation microstates during the aging process. By using a machine-learning algorithm, we identify four typical clusters of microstate patterns across different age groups and different frequency bands: left-to-right topographic MS1, right-to-left topographic MS2, anterior-posterior MS3 and fronto-central MS4. We observed a decreased alpha duration and an increased alpha occurrence for sensory-related microstate patterns (MS1 & MS2). Accordingly, theta and beta changes from MS1 & MS2 may be related to motor decline that increased with age. Furthermore, voluntary 'top-down' saliency/attention networks may be reflected by the increased MS3 & MS4 alpha occurrence and complementary beta activities. The findings of this study advance our knowledge of how the aging brain shows dysfunctions in neural state transitions. By leveraging the identified microstate patterns, this study provides new insights into predicting healthy aging and the potential neuropsychiatric cognitive decline., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

To eliminate multidrug-resistant bacteria of Acinetobacter baumannii , we screened 1100 Food and Drug Administration-approved small molecule drugs and accessed the broxyquinoline (Bq) efficacy in combination with various metal ions. Antibacterial tests demonstrated that the prepared Zn(Bq) 2 complex showed ultralow minimum inhibitory concentration of ~0.21 micrograms per milliliter with no resistance after 30 passages. We then constructed the nano zeolitic imidazolate framework-8 (ZIF-8) as a drug carrier of Zn(Bq) 2 and also incorporated the photosensitizer chlorin e6 (Ce6) to trace and boost the antibacterial effect. To further ensure the stable and targeted delivery, we genetically engineered outer membrane vesicles (OMVs) with the ability to selectively target A. baumannii . By coating the ZnBq/Ce6@ZIF-8 core with these OMV, the resulted drug (ZnBq/Ce6@ZIF-8@OMV) exhibited exceptional killing efficacy (>99.9999999%) of A. baumannii . In addition, in vitro and in vivo tests were also respectively carried out to inspect the remarkable efficacy of this previously unknown nanodrug in eradicating A. baumannii infections, including biofilms and meningitis.

Infants born at an extremely low gestational age (ELGA, < 29 weeks) are at an increased risk of intraventricular hemorrhage (IVH), and there is a need for standalone, safe, easy-to-use tools for monitoring cerebral hemodynamics. We have built a multi-wavelength multi-distance diffuse correlation spectroscopy device (MW-MD-DCS), which utilizes time-multiplexed, long-coherence lasers at 785, 808, and 853 nm, to simultaneously quantify the index of cerebral blood flow (CBF i ) and the hemoglobin oxygen saturation (SO 2 ). We show characterization data on liquid phantoms and demonstrate the system performance on the forearm of healthy adults, as well as clinical data obtained on two preterm infants., Competing Interests: At the time of the study, MAF had a financial interest in 149 Medical, Inc., a company developing DCS technology for assessing and monitoring CBF in newborn infants, which is now dissolved. MAF’s interests were reviewed and managed by Massachusetts General Hospital and Mass General Brigham in accordance with their conflict-of-interest policies., (© 2024 Optica Publishing Group.)

Inflammation-associated diseases encompass a range of infectious diseases and non-infectious inflammatory diseases, which continuously pose one of the most serious threats to human health, attributed to factors such as the emergence of new pathogens, increasing drug resistance, changes in living environments and lifestyles, and the aging population. Despite rapid advancements in mechanistic research and drug development for these diseases, current treatments often have limited efficacy and notable side effects, necessitating the development of more effective and targeted anti-inflammatory therapies. In recent years, the rapid development of nanotechnology has provided crucial technological support for the prevention, treatment, and detection of inflammation-associated diseases. Various types of nanoparticles (NPs) play significant roles, serving as vaccine vehicles to enhance immunogenicity and as drug carriers to improve targeting and bioavailability. NPs can also directly combat pathogens and inflammation. In addition, nanotechnology has facilitated the development of biosensors for pathogen detection and imaging techniques for inflammatory diseases. This review categorizes and characterizes different types of NPs, summarizes their applications in the prevention, treatment, and detection of infectious and inflammatory diseases. It also discusses the challenges associated with clinical translation in this field and explores the latest developments and prospects. In conclusion, nanotechnology opens up new possibilities for the comprehensive management of infectious and inflammatory diseases., (© 2024. The Author(s).)

Tachycardia-bradycardia syndrome (TBS) is a variant of sick sinus syndrome (SSS) characterized by alternating tachycardia and bradycardia. A few cases of SSS secondary to structural lesions in the medulla have been reported, but there has never been a reported case of the rare sign akin to TBS following acute non-medullary brainstem infarction. Furthermore, new-onset cardiac arrhythmias in stroke often presented in one continuous pattern - either as bradycardia or tachycardia, but instances of an alternating fashion have been rarely reported. We present the case of a 46-year-old female who developed severe dizziness with vomiting, diplopia, and slurred speech, which gradually worsened to quadriplegia, severe hypophonia, and dysphagia. Brain magnetic resonance imaging (MRI) demonstrated acute midbrain and pontine infarction. Except for neurological symptoms, the patient experienced unexpected TBS with the symptoms of excessive sweating, palpitations, and irritability without any other predisposing factors. The frequency of the episodes gradually declined until it spontaneously disappeared the 5 th day after admission. Given the unpredictable nature of the tachycardia and bradycardia, it was challenging to manage the arrythmias with medications. A pacemaker was recommended, but financial reasons led the patient to reject this option. Two weeks after antithrombotic therapy and rehabilitation, she was discharged with residual symptoms of diplopia, moderate dysarthria, mild quadriplegia, and no cardiac symptoms. Our case highlighted the occurrence of TBS as a new-onset arrhythmia that can manifest during the acute phase of non-medullary brainstem infarcts. Further research into brainstem lesions contributing to TBS is warranted us to elucidate the underlying mechanisms., Competing Interests: None., (AJTR Copyright © 2024.)

JOURNAL/nrgr/04.03/01300535-202507000-00025/figure1/v/2024-09-09T124005Z/r/image-tiff To investigate the mechanisms underlying the onset and progression of ischemic stroke, some methods have been proposed that can simultaneously monitor and create embolisms in the animal cerebral cortex. However, these methods often require complex systems and the effect of age on cerebral embolism has not been adequately studied, although ischemic stroke is strongly age-related. In this study, we propose an optical-resolution photoacoustic microscopy-based visualized photothrombosis methodology to create and monitor ischemic stroke in mice simultaneously using a 532 nm pulsed laser. We observed the molding process in mice of different ages and presented age-dependent vascular embolism differentiation. Moreover, we integrated optical coherence tomography angiography to investigate age-associated trends in cerebrovascular variability following a stroke. Our imaging data and quantitative analyses underscore the differential cerebrovascular responses to stroke in mice of different ages, thereby highlighting the technique's potential for evaluating cerebrovascular health and unraveling age-related mechanisms involved in ischemic strokes., (Copyright © 2025 Copyright: © 2025 Neural Regeneration Research.)

Plumula nelumbinis , a widely used traditional Chinese medicine known for its calming and nerve-soothing properties, contains essential oil as a primary component. However, research on P. nelumbinis essential oil (PNEO) is limited. This study aimed to investigate PNEO components, network target analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and antioxidant activity of P. nelumbinis from ten different habitats. GC-MS analysis identified 14 compounds in the essential oil, with CP12 (β-Sitosterol) having the highest concentration. Five compounds were identified for the first time in P. nelumbinis , with three of them reported for the first time in the Nelumbo . Network target analysis revealed 185 potential targets for 11 compounds and GO and KEGG enrichment analyses showed that PNEO was mainly located in the plasma membrane and could regulate a variety of molecular functions. KEGG pathway enrichment analysis revealed that the essential oil was primarily enriched in pathways related to cancer and the nervous system. PNEO demonstrated strong antioxidant activity, with N 8 (Fujiannanping) showing the highest ABTS scavenging capacity and N 7 (Hunanxiangtan) showing the highest DPPH radical scavenging capacity. Cell experiments showed that CP4, CP5 and CP10 had protective effects against H 2 O 2 -induced oxidative damage. The study suggests that P. nelumbinis from different regions may have slightly different pharmacological effects due to the presence of unique compounds, and further research is necessary to explore the potential therapeutic benefits of PNEO., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Twelve new hybrid compounds of Esculetin with nitric oxide (NO) donors and/or mitochondrial targeting groups were designed, synthesized, and evaluated for their anti-tumor activity and mechanism in vitro and in vivo . Notably, the most potent compound A11 exhibited nanomolar antiproliferative activity on triple-negative breast cancer (TNBC) MDA-MB-231 cells (IC 50 = 8 nM) with a strikingly selective inhibitory effect. The mechanism of A11 involves targeting MDA-MB-231 cells' mitochondria, releasing a high NO concentration, and increasing the expression of cyclophilin D (CypD), leading to increased reactive oxygen species (ROS) and triggering cancer cell apoptosis. Additionally, A11 could arrest the cell cycle at the G2/M phase to achieve anti-tumor effects. Moreover, A11 demonstrated a superior TNBC inhibition rate and diminished toxicity relative to doxorubicin (DOX) in vivo. In summary, A11 serves as a noteworthy contender for TNBC treatment with high potency and minimal toxicity.

Immune cells are essential for initiating and developing the fibrotic process by releasing cytokines and growth factors that activate fibroblasts and promote extracellular matrix deposition. Immunometabolism describes how metabolic alterations affect the function of immune cells and how inflammation and immune responses regulate systemic metabolism. The disturbed immune cell function and their interactions with other cells in the tissue microenvironment lead to the origin and advancement of fibrosis. Understanding the dysregulated metabolic alterations and interactions between fibroblasts and the immune cells is critical for providing new therapeutic targets for fibrosis. This review provides an overview of recent advances in the pathophysiology of fibrosis from the immunometabolism aspect, highlighting the altered metabolic pathways in critical immune cell populations and the impact of inflammation on fibroblast metabolism during the development of fibrosis. We also discuss how this knowledge could be leveraged to develop novel therapeutic strategies for treating fibrotic diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Feng, Chen, Huang, Zhang, Zheng and Xie.)

Introduction: Homocysteine (Hcy) is a critical factor for cardiovascular injury, and the elevation of Hcy in children will inevitably increase the risk of cardiovascular disease in adulthood. This study explored the effect of very low-mineral water on children's Hcy and cardiovascular health., Materials and Methods: This was a retrospective cohort study that recruited two groups of 10-13-year-old children who had consumed direct drinking water (DDW) in school for 4 years. The control group (NW) (119 boys, 110 girls) consumed normal DDW (conductivity 345 μs/cm). The very low-mineral water consumption group (VLW) (223 boys, 208 girls) consumed very low-mineral DDW (conductivity 40.0 μs/cm). Serum Hcy, Hcy metabolites, cofactors of Hcy metabolism, and cardiovascular biomarkers were assessed and standardized by age- and sex-specific Z-scores, and the differences between the two groups were analyzed with independent t -test. The relationships between Hcy metabolism biomarkers and key factors, cardiovascular biomarkers, serum Ca, and mineral intake were analyzed with linear regression., Results: Compared with the NW group, the VLW group had significantly higher serum Hcy, Apo-B, Apo-B/A1, and oxLDL, and lower serum 1,25,(OH) 2 D 3 , vitamin B6 and B12, 5-methyltetrahydrofolate, and Apo-A1. Serum Hcy was positively associated with serum Apo-B and Apo-B/A1, and negatively associated with Ca intake from water and serum 1,25,(OH) 2 D 3 ., Conclusion: This study suggested that drinking very low-mineral water may increase Hcy level and oxidative stress, worsen lipid profile, and threaten the cardiovascular system in children. Reducing 1,25,(OH) 2 D 3 , and disordering of calcium metabolism might play important roles. This study first established an association between demineralized drinking water and cardiovascular health in children, suggesting a new environmental concern risk to cardiovascular health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Huang, Tan, Wang, Lan, Luo, Wang, Zeng and Shu.)