Enzyme-Enabled Droplet Biobattery for Powering Synthetic Tissues.

Enzyme-enabled biobatteries are promising green options to power the next-generation of bioelectronics and implantable medical devices. However, existing power sources based on enzymatic biofuel chemistry exhibit limited scale-down feasibility due to the solid and bulky battery structures. Therefore, miniature and soft alternatives are needed for integration with implants and tissues. Here, a biobattery built from nanolitre droplets, fuelled by the enzyme-enabled oxidation of reduced nicotinamide adenine dinucleotide, generates electrical outputs and powers ion fluxes in droplet networks. Optimization of the droplet biobattery components ensures a stable output current of ~13,000 pA for over 24 h, representing a more than 600-fold increase in output over previous approaches, including light-driven processes. The enzyme-enabled droplet biobattery opens new avenues in bioelectronics and bioiontronics, exemplified by tasks such as the ability to drive electrochemical signal transmission in integrated synthetic tissues.

Methylisothiazolinone pollution inhibited root stem cells and regeneration through auxin transport modification in Arabidopsis thaliana.

Methylisothiazolinone (MIT) is a widely used preservative and biocide to prevent product degradation, yet its potential impact on plant growth remains poorly understood. In this study, we investigated MIT's toxic effects on Arabidopsis thaliana root growth. Exposure to MIT significantly inhibited Arabidopsis root growth, associated with reduced root meristem size and root meristem cell numbers. We explored the polar auxin transport pathway and stem cell regulation as key factors in root meristem function. Our findings demonstrated that MIT suppressed the expression of the auxin efflux carrier PIN1 and major root stem cell regulators (PLT1, PLT2, SHR, and SCR). Additionally, MIT hindered root regeneration by downregulating the quiescent center (QC) marker WOX5. Transcriptome analysis revealed MIT-induced alterations in gene expression related to oxidative stress, with physiological experiments confirming elevated reactive oxygen species (ROS) levels and increased cell death in root tips at concentrations exceeding 50 µM. In summary, this study provides critical insights into MIT's toxicity on plant root development and regeneration, primarily linked to modifications in polar auxin transport and downregulation of genes associated with root stem cell regulation.

The Novel-B-Cell-Related Gene Signature Predicts the Prognosis and Immune Status of Patients with Esophageal Carcinoma.

BACKGROUND: The current understanding of the prognostic significance of B cells and their role in the tumor microenvironment (TME) in esophageal carcinoma (ESCA) is limited. METHODS: We conducted a screening for B-cell-related genes through the analysis of single-cell transcriptome data. Subsequently, we developed a B-cell-related gene signature (BRGrisk) using LASSO regression analysis. Patients from The Cancer Genome Atlas cohort were divided into a training cohort and a test cohort. Patients were categorized into high- and low-risk groups based on their median BRGrisk scores. The overall survival was assessed using the Kaplan-Meier method, and a nomogram based on BRGrisk was constructed. Immune infiltration profiles between the risk groups were also compared. RESULTS: The BRGrisk prognostic model indicated significantly worse outcomes for patients with high BRGrisk scores (p < 0.001). The BRGrisk-based nomogram exhibited good prognostic performance. Analysis of immune infiltration revealed that patients in the high-BRGrisk group had notably higher levels of immune cell infiltration and were more likely to be in an immunoresponsive state. Enrichment analysis showed a strong correlation between the prognostic gene signature and cancer-related pathways. IC50 results indicated that patients in the low-BRGrisk group were more responsive to common drugs compared to those in the high-BRGrisk group. CONCLUSIONS: This study presents a novel BRGrisk that can be used to stratify the prognosis of ESCA patients and may offer guidance for personalized treatment strategies aimed at improving prognosis.

Association of sleep duration with Visceral Adiposity Index: a cross-sectional study based on the NHANES 2007-2018.

OBJECTIVE: We aimed to assess the associations between sleep duration and Visceral Adiposity Index (VAI). DESIGN: Cross-sectional study. SETTING: The National Health and Nutrition Examination Survey (2007-2018). PARTICIPANTS: A total 11 252 eligible participants who have complete information for sleep duration and VAI. OUTCOME MEASURE: The VAI index, which is sex-specific and takes into consideration factors such as waist circumference, body mass index, high-density lipoprotein cholesterol and triglycerides, was calculated in accordance with prior research. Multiple linear regressions and subgroup analyses were employed to evaluate the connection between the duration of sleep and the VAI. RESULTS: The mean sleep duration and VAI of included participants were 7.05 hours/day and 2.03, respectively. After adjusting for the sociodemographic, lifestyle and other covariates, short sleep was significantly linked to increased VAI (ß=0.15, 95% CI 0.01 to 0.28) in relation to middle sleep duration, whereas no significant association was found between long sleep duration and VAI. An L-shaped relationship was observed between sleep duration and VAI. When sleep duration was less than 7.5 hours/day, a negative association between sleep duration and VAI was obvious. However, when sleep duration was >7.5 hours/day, VAI was increased with a longer sleep duration, although it was not significant. CONCLUSIONS: An L-shaped relationship was observed between sleep duration and VAI, with insufficient sleep, being independently linked to a higher VAI. This implies that sleep deprivation might be associated with visceral adipose distribution and disfunction.

Deficiency of Secreted Phosphoprotein 1 Alleviates Hyperoxia-induced Bronchopulmonary Dysplasia in Neonatal Mice.

Bronchopulmonary dysplasia (BPD) is a common chronic lung disorder characterized by impaired proximal airway and bronchoalveolar development in premature births. Secreted phosphoprotein 1 (SPP1) is involved in lung development and lung injury events, while its role was not explored in BPD. For establishing the in vivo models of BPD, a mouse model of hyperoxia-induced lung injury was generated by exposing neonatal mice to hyperoxia for 7 days after birth. Alveolar myofibroblasts (AMYFs) were treated with hyperoxia to establish the in vitro models of BPD. Based on the scRNA-seq analysis of lungs of mice housed under normoxia or hyperoxia conditions, mouse macrophages and fibroblasts were main different cell clusters between the two groups, and differentially expressed genes in fibroblasts were screened. Further GO and KEGG enrichment analysis revealed that these differentially expressed genes were mainly enriched in the pathways related to cell proliferation, apoptosis as well as the PI3K-AKT and ERK/MAPK pathways. SPP1 was found up-regulated in the lung tissues of hyperoxia mice. We also demonstrated the up-regulation of SPP1 in the BPD patients, the mouse model of hyperoxia-induced lung injury, and hyperoxia-induced cells. SPP1 deficiency was revealed to reduce the hyperoxia-induced apoptosis, oxidative stress and inflammation and increase the viability of AMYFs. In the mouse model of hyperoxia induced lung injury, SPP1 deficiency was demonstrated to reverse the hyperoxia-induced alveolar growth disruption, oxidative stress and inflammation. Overall, SPP1 exacerbates BPD progression in vitro and in vivo by regulating oxidative stress and inflammatory response via the PI3K-AKT and ERK/MAPK pathways, which might provide novel therapeutic target for BPD therapy.

Effect of platelet-rich fibrin on the recovery after third molar surgery: A systematic review and meta-analysis.

This meta-analysis aimed to elucidate the effects of platelet-rich fibrin (PRF) on the recovery of alveolar bone after surgical removal of the mandibular third molars. PubMed, Cochrane Library, Web of Science, and Embase databases were searched from the inception to February 2023 for relevant studies on the application of PRF after the extraction of impacted mandibular third molars, with the language limited to English. Literature screening was conducted by two independent researchers. The Cochrane risk-of-bias tool was adopted for quality evaluation, and Stata 15.0 was used for statistical analysis. A total of 33 randomized controlled trials were included in the present study. Following surgical removal of the mandibular third molars, 1139 tooth sockets were filled with PRF, while 1138 sockets were sutured after conventional saline irrigation. The meta-analyses showed that PRF can relieve pain [(RR 0.454; 95% CI 0.23, 0.891); (SMD -0.74; 95% CI -0.97, 0.52)], improve swelling (SMD -1.48; 95% CI -1.90, -1.06), alleviate trismus (SMD -0.35; 95% CI -0.51, -0.19), reduce dry socket (SMD -0.18; 95% CI -030, -0.05), and promote bone tissue healing (SMD 2.34; 95% CI 0.18, 4.51). The current study confirms that PRF can reduce some postoperative complications. Local application of PRF after lower third molar extraction is a viable method for relieving pain and swelling, reducing the incidence of dry socket and trismus, and increasing bone density. However, whether it can promote soft tissue healing remains unclear. For patients undergoing complicated surgical extraction, local application of PRF into the sockets might be a good option.

Corrigendum: Dynamic evolution of left ventricular strain and microvascular perfusion assessed by speckle tracking echocardiography and myocardial contrast echocardiography in diabetic rats: effect of dapagliflozin.

[This corrects the article DOI: 10.3389/fcvm.2023.1109946.].

Distribution and migration of rare earth elements in sediment profile near a decommissioned uranium hydrometallurgical site in South China: Environmental implications.

Rare earth elements have garnered increasing attention due to their strategic properties and chronic toxicity to humans. To better understand the content, migration, and ecological risk of rare earth elements in a 180 cm depth sediment profile downstream of a decommissioned uranium hydrometallurgical site in South China, X-ray powder diffraction (XRD) and High-resolution transmission electron microscope (HRTEM) were additionally used to quantify and clarify the mineral composition features. The results showed a high enrichment level of total rare earth elements in the sediment depth profile (range: 129.6-1264.3 mg/kg); the concentration variation of light rare earth elements was more dependent on depth than heavy rare earth elements. Overall, there was an obvious enrichment trend of light rare earth elements relative to heavy rare earth elements and negative anomalies of Ce and Eu. The fractionation and anomaly of rare earth elements in sediments were closely related to the formation and weathering of iron-bearing minerals and clay minerals, as confirmed by the correlation analysis of rare earth elements with Fe (r2 = 0.77-0.90) and Al (r2 = 0.50-0.71). The mineralogical composition of sediments mainly consisted of quartz, feldspar, magnetite, goethite, and hematite. Pollution assessment based on the potential ecological risk index, pollution load index (PLI), enrichment factor, and geological accumulation index (Igeo) showed that almost all the sediments had varying degrees of pollution and a high level of ecological risk. This study implied that continued environmental supervision and management are needed to secure the ecological health in terms of rare earth elements enrichment around a decommissioned uranium hydrometallurgical site. The findings may provide valuable insights for other uranium mining and hydrometallurgical areas globally.

Repairing gut barrier by traditional Chinese medicine: roles of gut microbiota.

Gut barrier is not only part of the digestive organ but also an important immunological organ for the hosts. The disruption of gut barrier can lead to various diseases such as obesity and colitis. In recent years, traditional Chinese medicine (TCM) has gained much attention for its rich clinical experiences enriched in thousands of years. After orally taken, TCM can interplay with gut microbiota. On one hand, TCM can modulate the composition and function of gut microbiota. On the other hand, gut microbiota can transform TCM compounds. The gut microbiota metabolites produced during the actions of these interplays exert noticeable pharmacological effects on the host especially gut barrier. Recently, a large number of studies have investigated the repairing and fortifying effects of TCM on gut barriers from the perspective of gut microbiota and its metabolites. However, no review has summarized the mechanism behand this beneficiary effects of TCM. In this review, we first briefly introduce the unique structure and specific function of gut barrier. Then, we summarize the interactions and relationship amidst gut microbiota, gut microbiota metabolites and TCM. Further, we summarize the regulative effects and mechanisms of TCM on gut barrier including physical barrier, chemical barrier, immunological barrier, and microbial barrier. At last, we discuss the effects of TCM on diseases that are associated gut barrier destruction such as ulcerative colitis and type 2 diabetes. Our review can provide insights into TCM, gut barrier and gut microbiota.

Cognitive impairment and the gut-brain axis during 2014-2023: a bibliometric analysis.

Background: The burden on society grows as the number of individuals with cognitive impairment rises. Numerous research have discovered a connection between cognitive impairment and the gut-brain axis, which is useful in examining the pathophysiology of cognitive impairment and potential therapeutic approaches. As a result, this article explores developments and trends in the research concerning the gut-brain axis and cognitive impairment through a bibliometric analysis of the contributions made by various countries/regions, institutions, authors, and journals. Methods: We looked for articles on gut-brain axis and cognitive impairment from 2014 to 2023 in the Web of Science Core Collection. For the descriptive analysis, figures and tables were taken using GraphPad Prism 6 and WPS Office 2024. For the visual analysis of the countries/regions, institutions, authors, and keywords, VOSviewer was utilized. Results: We obtained 458 publications from 1 January 2014 to 9 September 2023. The country with the most publications (175, 38.21%) was China. The country with the greatest total number of citations (3,138, 17.22%) was the United States of America. The highest number of articles (15, 3.26%) was issued by Zhejiang University. The most published first author is Karsas M. In this field, Nutrients have published the most articles (24). The most often occurring keywords include "Alzheimer's disease," "cognitive impairment," "gut microbiota," "inflammation," "diet," etc. "Stroke," "tau," "probiotics," "exercise," "fecal microbiota transplantation," etc. emerged later. Conclusion: An increasing amount of research has focused on the connection between cognitive impairment and the gut-brain axis. In this area, the United States of America and China have both made significant contributions. The author team's collaboration has to be improved. Our study contributes to understanding the field's current state and predicting its future trend.

A kinetics-coupled multi-surface complexation model deciphering arsenic adsorption and mobility across soil types.

The diversity of soil adsorbents for arsenic (As) and the often-overlooked influence of manganese (Mn) on As(III) oxidation impose challenges in predicting As adsorption in soils. This study uses Mössbauer spectroscopy, X-ray diffraction of oriented clay, and batch experiments to develop a kinetic coupled multi-surface complexation model that characterizes As adsorbents in natural soils and quantifies their contributions to As adsorption. The model integrates dynamic adsorption behaviors and Mn-oxide interactions with unified thermodynamic and kinetic parameters. The results indicate that As adsorption is governed by five primary adsorbents: poorly crystalline Fe oxides, well crystalline Fe oxides, Fe-rich clay, Fe-depletion clay, and organic carbon (OC). Fe oxides dominate As adsorption at low As concentrations. However, at higher As concentrations, soils from carbonate strata, with higher content of Fe-rich clay, exhibit stronger As adsorption capabilities than soils from Quaternary sediment strata. The enrichment in Fe-rich clay can enhance the resistance of adsorbed As to reduction processes affecting Fe oxides. Additionally, extensive redox cycles in paddy fields increase OC levels, enhancing their As adsorption compared to upland fields. This model framework provides novel insights into the intricate dynamics of As within soils and a versatile tool for predicting As adsorption across diverse soils.

Module control of network analysis in psychopathology.

The network approach to characterizing psychopathology departs from traditional latent categorical and dimensional approaches. Causal interplay among symptoms contributed to dynamic psychopathology system. Therefore, analyzing the symptom clusters is critical for understanding mental disorders. Furthermore, despite extensive research studying the topological features of symptom networks, the control relationships between symptoms remain largely unclear. Here, we present a novel systematizing concept, module control, to analyze the control principle of the symptom network at a module level. We introduce Module Control Network (MCN) to identify key modules that regulate the network's behavior. By applying our approach to a multivariate psychological dataset, we discover that non-emotional modules, such as sleep-related and stress-related modules, are the primary controlling modules in the symptom network. Our findings indicate that module control can expose central symptom cluster governing psychopathology network, offering novel insights into the underlying mechanisms of mental disorders and individualized approach to psychological interventions.

Gtie-Rt: A comprehensive graph learning model for predicting drugs targeting metabolic pathways in human.

Drugs often target specific metabolic pathways to produce a therapeutic effect. However, these pathways are complex and interconnected, making it challenging to predict a drug's potential effects on an organism's overall metabolism. The mapping of drugs with targeting metabolic pathways in the organisms can provide a more complete understanding of the metabolic effects of a drug and help to identify potential drug-drug interactions. In this study, we proposed a machine learning hybrid model Graph Transformer Integrated Encoder (GTIE-RT) for mapping drugs to target metabolic pathways in human. The proposed model is a composite of a Graph Convolution Network (GCN) and transformer encoder for graph embedding and attention mechanism. The output of the transformer encoder is then fed into the Extremely Randomized Trees Classifier to predict target metabolic pathways. The evaluation of the GTIE-RT on drugs dataset demonstrates excellent performance metrics, including accuracy (>95%), recall (>92%), precision (>93%) and F1-score (>92%). Compared to other variants and machine learning methods, GTIE-RT consistently shows more reliable results.

Planning biosynthetic pathways of target molecules based on metabolic reaction prediction and AND-OR tree search.

Bioretrosynthesis problem is to predict synthetic routes using substrates for given natural products (NPs). However, the huge number of metabolic reactions leads to a combinatorial explosion of searching space, which is high time-consuming and costly. Here, we propose a framework called BioRetro to predict bioretrosynthesis pathways using a one-step bioretrosynthesis network, termed HybridMLP combined with AND-OR tree heuristic search. The HybridMLP predicts precursors that will produce the target NPs, while the AND-OR tree generates the iterative multi-step biosynthetic pathways. The one-step bioretrosynthesis prediction experiments are conducted on MetaNetX dataset by using HybridMLP, which achieves 46.5%, 74.6%, 81.6% in terms of the top-1, top-5, top-10 accuracies. The great performance demonstrates the effectiveness of HybridMLP in one-step bioretrosynthesis. Besides, the evaluation of two benchmark datasets reveals that BioRetro can significantly improve the speed and success rate in predicting biosynthesis pathways. In addition, the BioRetro is further shown to find the synthetic pathway of compounds, such as ginsenoside F1 with the same substrates as reported but different enzymes, which may be the novel potential enzyme to have better catalytic performance.

Determination of six short-chain fatty acids in rat feces using headspace solid-phase dynamic extraction coupled with GC-MS.

Short-chain fatty acids (SCFAs) are organic acids with carbon atoms less than six, released through fermentation products by intestinal microbiome, having multiple physiological activities. Considering weak acidity and high volatility, derivatization or liquid-liquid extraction is essential, which is time consuming. Headspace-solid-phase dynamic extraction (HS-SPDE) coupled with gas chromatography-mass spectrometry is automated and effortless to determine SCFAs in rat feces. The extraction procedure is performed by aspirating and discharging the headspace cyclically through a steel needle, coated with an inner polyethylene glycol sorbent. The key parameters of SPDE were optimized including coating type, incubation time and temperature, and number of extraction strokes. Besides, salting-out was conducted. Then, a method by HS-SPDE-GC-MS was established and validated. It only took 3-min incubation time, 4.5 min extraction time, and 13 min chromatographic separation in a run. The recovery, linearity, limit of quantification, and stability were evaluated. Then, the proposed method was applied to analyze rat feces including 18 rats with liver injury and 23 normal controls. Mann-Whitney U test indicated that the concentrations of six SCFAs in normal rat feces were higher than those with liver injury. This method provides a choice for fast, solvent-free, automated, and high-throughput analysis of SCFAs.

Comparative efficacy of modified Noel's technique and matrix phenolization on onychocryptosis: a retrospective study.

BACKGROUND: Onychocryptosis is a common pathological condition requiring clinical intervention. Selecting an appropriate and effective treatment based on individual patient circumstances is crucial. METHODS: We compared the efficacy and safety of the modified Noel's technique and matrix phenolization in 107 participants with onychocryptosis. Participants were divided into two groups: 75 nails (73 patients) were treated with the modified Noel's technique (modified Noel's group), while 42 nails (34 patients) were treated with matrix phenolization (Phenol group). Outcomes on clinical cure rates and postoperative complications from both groups were collected. Additionally, the efficacy of the modified Noel's technique was assessed in 31 nails with stage IV onychocryptosis. RESULTS: After 18 months, among the remaining 102 patients (110 nails), the modified Noel's group exhibited fewer complications (5.88% vs. 45.2%, P < 0.001) with similar cure rates (P = 0.62). Furthermore, there was a shorter healing time in the modified Noel's group (13.5 ± 1.4 vs. 27.6 ± 2.3 days, P < 0.001). Postoperative pain was notable in the modified Noel's group on the first postoperative day (P < 0.001), with a significant decrease in the pain score 2 weeks after surgery (P = 0.407). Postoperative nail plate narrowing was observed in the Phenol group (33%). Moreover, the modified Noel's technique achieved a 100% cure rate in stage IV patients. CONCLUSIONS: The modified Noel's technique, offering precise excision of the proliferative nail fold and strategic suturing, is suitable for stage IV patients and for those who find significant aesthetic impact unacceptable following narrowed plate postmatrix phenolization.

Systematic identification and functional analysis of root meristem growth factors (RGFs) reveals role of PgRGF1 in modulation of root development and ginsenoside production in Panax ginseng.

Panax ginseng C.A. Mey., known for its medicinal and dietary supplement properties, primarily contains pharmacologically active ginsenosides. However, the regulatory mechanisms linking ginseng root development with ginsenoside biosynthesis are still unclear. Root meristem growth factors (RGFs) are crucial for regulating plant root growth. In our study, we identified five ginseng RGF peptide sequences from the ginseng genome and transcriptome libraries. We treated Arabidopsis and ginseng adventitious roots with exogenous Panax ginseng RGFs (PgRGFs) to assess their activities. Our results demonstrate that PgRGF1 influences gravitropic responses and reduces lateral root formation in Arabidopsis. PgRGF1 has been found to restrict the number and length of ginseng adventitious root branches in ginseng. Given the medicinal properties of ginseng, We determined the ginsenoside content and performed transcriptomic analysis of PgRGF1-treated ginseng adventitious roots. Specifically, the total ginsenoside content in ginseng adventitious roots decreased by 19.98 % and 63.71 % following treatments with 1 µM and 10 µM PgRGF1, respectively, compared to the control. The results revealed that PgRGF1 affects the accumulation of ginsenosides by regulating the expression of genes associated with auxin transportation and ginsenoside biosynthesis. These findings suggest that PgRGF1, as a peptide hormone regulator in ginseng, can modulate adventitious root growth and ginsenoside accumulation.

Surface-based multimodal protein-ligand binding affinity prediction.

MOTIVATION: In the field of drug discovery, accurately and effectively predicting the binding affinity between proteins and ligands is crucial for drug screening and optimization. However, current research primarily utilizes representations based on sequence or structure to predict protein-ligand binding affinity, with relatively less study on protein surface information, which is crucial for protein-ligand interactions. Moreover, when dealing with multimodal information of proteins, traditional approaches typically concatenate features from different modalities in a straightforward manner without considering the heterogeneity among them, which results in an inability to effectively exploit the complementary between modalities. RESULTS: We introduce a novel multimodal feature extraction (MFE) framework that, for the first time, incorporates information from protein surfaces, 3D structures, and sequences, and uses cross-attention mechanism for feature alignment between different modalities. Experimental results show that our method achieves state-of-the-art performance in predicting protein-ligand binding affinity. Furthermore, we conduct ablation studies that demonstrate the effectiveness and necessity of protein surface information and multimodal feature alignment within the framework. AVAILABILITY AND IMPLEMENTATION: The source code and data are available at https://github.com/Sultans0fSwing/MFE.

Piracetam reduces oxidative stress and mitochondrial function impairment in an in vitro model of vascular dementia.

Vascular dementia (VaD) is the most common cause of dementia in older adults. Due to the lack of effective treatment options, there is an urgent need to find an effective pharmaceutical compound to combat VaD. Piracetam has been reported to improve impaired cognitive function in a variety of conditions in both human and animal models. However, the role and mechanism of Piracetam in VaD remain unclear. Therefore this study aimed to elucidate the effect of Piracetam on a cellular model of VaD in vitro. We found that Piracetam enhanced the growth of OGD-stimulated SH-SY5Y cells. In addition, Piracetam inhibited the oxidative stress of OGD-stimulated SH-SY5Y cells. Further, Piracetam improved mitochondrial function of OGD-stimulated SH-SY5Y cells. Mechanistically, Piracetam inhibited the PI3K/Akt/mTOR pathway in OGD-stimulated SH-SY5Y cells. Collectively, Piracetam improved oxidative stress and mitochondrial dysfunction of OGD-stimulated SH-SY5Y cells through PI3K/Akt/mTOR axis. Hence, Piracetam has the potential to serve as a promising drug of VaD.