Mechanism investigation of anti-NAFLD of Shugan Yipi Granule based on network pharmacology analysis and experimental verification.

As a classical traditional Chinese patent medicine, Shugan Yipi Granule is widely used in China to treat non-alcoholic fatty liver disease (NAFLD) recently. Our previous study confirmed that Shugan Yipi Granule are effective in NAFLD. However, its underlying mechanism is still unknown. This study aims to investigate the mechanism of Shugan Yipi Granule on NAFLD based on network pharmacology prediction, liquid chromatography-mass spectrometry (LC-MS) analysis and in vitro verification. We obtained the active ingredients and targets of Shugan Yipi Granule and NAFLD from 6 traditional Chinese medicine databases, and the crucial components and targets screened by protein-protein interaction (PPI) network were used for molecular docking. Plasma metabolomics of NAFLD patients treated with Shugan Yipi Granule for one month was analyzed using LC-MS methods and MetaboAnalyst 4.0 to obtain significant differential metabolites and pathways. Finally, free fatty acid (FFA) induced HepG2 cells were treated with different concentrations of quercetin and kaempferol, then oil red o (ORO) and triglyceride (TG) level were tested to verify the lipid deposition of the cell. Network pharmacology analysis showed that the main active ingredients of Shugan Yipi Granule include quercetin, kaempferol and other 58 ones, as well as 188 potential targets. PI3K/Akt signaling pathway was found to be the most relevant pathway for the treatment of NAFLD. Non-targeted metabolomics showed that quercetin and kaempferol were significantly up-regulated differential metabolites and were involved in metabolic pathways such as thyroid hormone signaling. In vitro results showed that quercetin, kaempferol were effective in reducing lipid deposition and TG content by inhibiting cellular fatty acid uptake. Ultimately, with the network pharmacology and serum metabolomics analysis, quercetin and kaempferol were found to be the important active ingredients and significantly up-regulated differential metabolites of Shugan Yipi Granule against NAFLD, which we inferred that they may regulate NAFLD through PI3K/Akt signaling pathway and thyroid hormone metabolism pathway. The in vitro experiment verification results showed that quercetin and kaempferol attenuated the lipid accumulation and TG content by inhibiting the fatty acid uptake in the FFA-induced HepG2 cell. Current study provides the necessary experimental basis for subsequent in-depth mechanism research.

Hyd/UBR5 defines a tumor suppressor pathway that links Polycomb repressive complex to regulated protein degradation in tissue growth control and tumorigenesis.

Tumor suppressor genes play critical roles in normal tissue homeostasis, and their dysregulation underlies human diseases including cancer. Besides human genetics, model organisms such as Drosophila have been instrumental in discovering tumor suppressor pathways that were subsequently shown to be highly relevant in human cancer. Here we show that hyperplastic disc (Hyd), one of the first tumor suppressors isolated genetically in Drosophila and encoding an E3 ubiquitin ligase with hitherto unknown substrates, and Lines (Lin), best known for its role in embryonic segmentation, define an obligatory tumor suppressor protein complex (Hyd-Lin) that targets the zinc finger-containing oncoprotein Bowl for ubiquitin-mediated degradation, with Lin functioning as a substrate adaptor to recruit Bowl to Hyd for ubiquitination. Interestingly, the activity of the Hyd-Lin complex is directly inhibited by a micropeptide encoded by another zinc finger gene, drumstick (drm), which functions as a pseudosubstrate by displacing Bowl from the Hyd-Lin complex, thus stabilizing Bowl. We further identify the epigenetic regulator Polycomb repressive complex1 (PRC1) as a critical upstream regulator of the Hyd-Lin-Bowl pathway by directly repressing the transcription of the micropeptide drm Consistent with these molecular studies, we show that genetic inactivation of Hyd, Lin, or PRC1 resulted in Bowl-dependent hyperplastic tissue overgrowth in vivo. We also provide evidence that the mammalian homologs of Hyd (UBR5, known to be recurrently dysregulated in various human cancers), Lin (LINS1), and Bowl (OSR1/2) constitute an analogous protein degradation pathway in human cells, and that OSR2 promotes prostate cancer tumorigenesis. Altogether, these findings define a previously unrecognized tumor suppressor pathway that links epigenetic program to regulated protein degradation in tissue growth control and tumorigenesis.

Application of N-doped NiCo2O4/NiO/Co3O4composites rich in oxygen vacancies in electromagnetic wave absorption.

In this work, N-doped and oxygen vacancy-rich NiCo2O4/NiO/Co3O4composites are synthesized by the direct calcination method. Noticeably, by changing the additive concentrations of urea dissolved in DMF (N-N dimethylformamide), the electromagnetic wave (EMW) absorption abilities of NiCo2O4/NiO/Co3O4composite effectively. A maximum reflection loss (RLmax) value at 12.94 GHz for a 2.8 mm thick sheet is -29.76 dB, while its effective absorption bandwidth (RL < -10 dB) reaches 4.21 GHz. In-depth research of possible mechanisms of EMW absorption enhancement. Owing to its simple preparation method and superb EMW absorption properties, the NiCo2O4/NiO/Co3O4composites have a chance to be suitable candidates for high-property EMW absorbers.

Novel genes involved in vascular dysfunction of the middle temporal gyrus in Alzheimer's disease: transcriptomics combined with machine learning analysis.

Studies have shown that vascular dysfunction is closely related to the pathogenesis of Alzheimer's disease. The middle temporal gyrus region of the brain is susceptible to pronounced impairment in Alzheimer's disease. Identification of the molecules involved in vascular aberrance of the middle temporal gyrus would support elucidation of the mechanisms underlying Alzheimer's disease and discovery of novel targets for intervention. We carried out single-cell transcriptomic analysis of the middle temporal gyrus in the brains of patients with Alzheimer's disease and healthy controls, revealing obvious changes in vascular function. CellChat analysis of intercellular communication in the middle temporal gyrus showed that the number of cell interactions in this region was decreased in Alzheimer's disease patients, with altered intercellular communication of endothelial cells and pericytes being the most prominent. Differentially expressed genes were also identified. Using the CellChat results, AUCell evaluation of the pathway activity of specific cells showed that the obvious changes in vascular function in the middle temporal gyrus in Alzheimer's disease were directly related to changes in the vascular endothelial growth factor (VEGF)A-VEGF receptor (VEGFR) 2 pathway. AUCell analysis identified subtypes of endothelial cells and pericytes directly related to VEGFA-VEGFR2 pathway activity. Two subtypes of middle temporal gyrus cells showed significant alteration in AD: endothelial cells with high expression of Erb-B2 receptor tyrosine kinase 4 (ERBB4high) and pericytes with high expression of angiopoietin-like 4 (ANGPTL4high). Finally, combining bulk RNA sequencing data and two machine learning algorithms (least absolute shrinkage and selection operator and random forest), four characteristic Alzheimer's disease feature genes were identified: somatostatin (SST), protein tyrosine phosphatase non-receptor type 3 (PTPN3), glutinase (GL3), and tropomyosin 3 (PTM3). These genes were downregulated in the middle temporal gyrus of patients with Alzheimer's disease and may be used to target the VEGF pathway. Alzheimer's disease mouse models demonstrated consistent altered expression of these genes in the middle temporal gyrus. In conclusion, this study detected changes in intercellular communication between endothelial cells and pericytes in the middle temporal gyrus and identified four novel feature genes related to middle temporal gyrus and vascular functioning in patients with Alzheimer's disease. These findings contribute to a deeper understanding of the molecular mechanisms underlying Alzheimer's disease and present novel treatment targets.

Gut Microbiota Mediate Plutella xylostella Susceptibility to Bt Cry1Ac Protoxin and Exopolysaccharides.

Exopolysaccharides (EPSs) are carbohydrate polymers that are synthesized and secreted into the extracellular during the growth of microorganisms. Bacillus thuringiensis (Bt) is a type of entomopathogenic bacterium, that produces various insecticidal proteins and EPSs. In our previous study, the EPSs produced by Bt strains were first found to enhance the toxicity of insecticidal crystal proteins against Plutella xylostella. However, the response of the intestinal bacterial communities of P. xylostella under the action of EPSs is still unelucidated. In this study, 16S rRNA amplicon sequencing was used to characterize the intestinal bacterial communities in P. xylostella treated with EPSs alone, Cry1Ac protoxin alone, and both the Cry1Ac protoxin and EPSs. Compared with the control group, alpha diversity indices, the Chao1 and ACE indices were significantly altered after treatment with EPSs alone, and no significant difference was observed between the groups treated with Cry1Ac protoxin alone and Cry1Ac protoxin + EPSs. However, compared with the gut bacterial community feeding on Cry1Ac protoxin alone, the relative abundance of 31 genera was significantly changed in the group treated with Cry1Ac protoxin and EPSs. The intestinal bacteria, through the oral of Cry1Ac protoxin and EPSs, significantly enhanced the toxicity of the Cry1Ac protoxin towards the axenic P. xylostella. In addition, the relative abundance of the 16S rRNA gene in the chloroplasts of Brassica campestris decreased after adding EPSs. Taken together, these results show the vital contribution of the gut microbiota to the Bt strain-killing activity, providing new insights into the mechanism of the synergistic insecticidal activity of Bt proteins and EPSs.

Lingguizhugan Decoction Improved Obesity by Modulating the Gut Microbiota and its Metabolites in Mice.

BACKGROUND: The global obese population is rapidly increasing, urgently requiring the development of effective and safe weight-loss medications. The classic Chinese medicine formulation Lingguizhugan De-coction has exerted a significant anti-obesity effect. However, the underlying mechanism is still unclear. OBJECTIVE: This study aimed to explore the mechanism of LGZGD in the treatment of obesity based on the gut microbiota and its metabolites. METHODS: Three different dosages of LGZGD were gavaged to ob/ob mice for 8 weeks. Body mass and visceral fat mass were evaluated. Additionally, the changes in gut microbiota, fecal and plasma metabolites in mice after LGZGD treatment were analyzed by metagenomics and non-targeted metabolomics. RESULTS: The results demonstrated a significant anti-obesity effect of LGZGD treatment in ob/ob mice. Fur-thermore, the metagenomic analysis revealed that LGZGD reduced the ratio of Firmicutes / Bacteroidetes (F to B) in the gut, restored gut microbiota diversity, and identified 3 enriched KEGG pathways, including energy metabolism, lipid metabolism, and energy production and conversion pathways. Based on non-targeted metab-olomics analysis, 20 key metabolites in the feces and 30 key metabolites in the plasma responding to LGZGD treatment were identified, and the levels of Eicosapentaenoic acid (EPA) and Myristoleic acid (MA) might be the metabolites related to gut microbiota after LGZGD treatment. Their biological functions were mainly re-lated to the metabolism pathway. CONCLUSIONS: These findings suggested that LGZGD had therapeutic potential for obesity. The mechanism of LGZGD alleviating obesity was associated with improving dysbiosis of the gut microbiota. LDZGD affected gut microbiota-derived metabolites of EPA and MA and may act on energy metabolism pathways.

Effect and Mechanism of 6-Gingerol against Precancerous Lesions of Gastric Cancer Based on Network Pharmacology and In Vitro Experiment.

BACKGROUND: Precancerous Lesions of Gastric Cancer (PLGC) are critical in the secondary prevention of gastric cancer. Despite the notable effects of natural products on PLGC, the specific mechanisms by which compounds, like 6-gingerol, influence these lesions are not fully understood. AIMS: This study aimed to confirm the effect and mechanism of 6-gingerol in the treatment of precancerous lesions of gastric cancer (PLGC). OBJECTIVE: The objective of this study was to elucidate the effects and mechanisms of 6-gingerol against PLGC using network pharmacology and in vitro experiments. METHODS: We employed network pharmacology to identify potential targets and pathways influenced by 6-gingerol, followed by validation through in vitro experiments using a PLGC cell model. RESULTS: Network pharmacology analysis highlighted the PI3K/Akt signaling pathway as significantly influenced by 6-gingerol. In vitro experiments confirmed that 6-gingerol effectively inhibited proliferation, invasion, and metastasis of MC cells, promoted apoptosis, and induced cell cycle arrest, primarily through modulation of the PI3K/Akt pathway. Statistical analysis revealed significant inhibition (p < 0.05) across these cellular processes in a dose-dependent manner. CONCLUSION: This study demonstrated that 6-gingerol acts as an effective agent against PLGC, with clear dose-dependent effects that pave the way for further experimental and clinical exploration.

Habitat radiomics and deep learning fusion nomogram to predict EGFR mutation status in stage I non-small cell lung cancer: a multicenter study.

Develop a radiomics nomogram that integrates deep learning, radiomics, and clinical variables to predict epidermal growth factor receptor (EGFR) mutation status in patients with stage I non-small cell lung cancer (NSCLC). We retrospectively included 438 patients who underwent curative surgery and completed driver-gene mutation tests for stage I NSCLC from four academic medical centers. Predictive models were established by extracting and analyzing radiomic features in intratumoral, peritumoral, and habitat regions of CT images to identify EGFR mutation status in stage I NSCLC. Additionally, three deep learning models based on the intratumoral region were constructed. A nomogram was developed by integrating representative radiomic signatures, deep learning, and clinical features. Model performance was assessed by calculating the area under the receiver operating characteristic (ROC) curve. The established habitat radiomics features demonstrated encouraging performance in discriminating between EGFR mutant and wild-type, with predictive ability superior to other single models (AUC 0.886, 0.812, and 0.790 for the training, validation, and external test sets, respectively). The radiomics-based nomogram exhibited excellent performance, achieving the highest AUC values of 0.917, 0.837, and 0.809 in the training, validation, and external test sets, respectively. Decision curve analysis (DCA) indicated that the nomogram provided a higher net benefit than other radiomics models, offering valuable information for treatment.

STIL facilitates the development and malignant progression of triple-negative breast cancer through activation of Fanconi anemia pathway via interacting with KLF16.

BACKGROUND: STIL is an important cell cycle-regulating protein specifically recruited to the mitotic centrosome to promote the replication of centrioles in dividing cells. However, the potential role of STIL in the regulation of the biological functions of triple-negative breast cancer remains still unclear. METHODS: We screened for differentially expressed STIL in the Cancer Genome Atlas database. The expression of STIL protein in 10 pairs of breast cancer tissues and adjacent normal tissues was further assessed by western blotting. Functionally, the knockdown and overexpression of STIL have been used to explore the effects of STIL on breast cancer cell proliferation, migration, and invasion. Mechanistically, RNA-seq, dual-luciferase reporter assay, chromatin immunoprecipitation assay, mass spectrometry, immunoprecipitation assay, and DNA pull-down assay were performed. RESULTS: Breast cancer tissues and cells have higher STIL expression than normal tissues and cells. STIL knockdown impairs breast cancer cell growth, migration, and invasion, whereas STIL overexpression accelerates these processes. STIL promotes breast cancer progression by regulating FANCD2 expression, and exploration of its molecular mechanism demonstrated that STIL interacts with KLF16 to regulate the expression of FANCD2. CONCLUSIONS: Collectively, our findings identified STIL as a critical promoter of breast cancer progression that interacts with KLF16 to regulate Fanconi anemia pathway protein FANCD2. In summary, STIL is a potential novel biomarker and therapeutic target for breast cancer.

Coupled physicochemical dual-crosslinking Ti3C2Tx composite aerogels for the selective adsorption of gallium ions in acid fly ash leaching.

Herein, in order to extract Ga3+ from acid fly ash leaching, we propose a functionalized Ti3C2Tx-based MXene composite aerogel adsorbent for Ga3+ adsorption. The prepared physicochemical dual-crosslinking network aerogel MPHG-40 possesses good Ga3+ adsorption performance (132.52 mg g-1) at the pH of 3 and Ga3+ initial concentration of 50 mg L-1 within 6 h. After five adsorption-desorption cycles, the material shows good mass retention and a 95.65 % retention of its initial adsorption capacity, compared to most reported adsorbents. The optimized adsorbent realized good selective adsorption of Ga3+ against Cu2+, Zn2+, Fe3+, and Al3+ in a simulated acid fly ash leaching with the selective coefficient of 8.63, 96.10, 4.49, and 28.30, respectively. The adsorption may comply with a combined mechanism of physical adsorption, electrostatic interactions, ion-exchange mechanism, and ligand chelation, dominated by chemical adsorption, as identified by theoretical calculations based on density functional theory and experimental data. The three-dimensional solid adsorbent constructed in this study provides a new strategy for selective adsorption of Ga3+, making it possible to be applied to solid waste utilization of fly ash.

Multi-Instance Learning for Vocal Fold Leukoplakia Diagnosis Using White Light and Narrow-Band Imaging: A Multicenter Study.

OBJECTIVES: Vocal fold leukoplakia (VFL) is a precancerous lesion of laryngeal cancer, and its endoscopic diagnosis poses challenges. We aim to develop an artificial intelligence (AI) model using white light imaging (WLI) and narrow-band imaging (NBI) to distinguish benign from malignant VFL. METHODS: A total of 7057 images from 426 patients were used for model development and internal validation. Additionally, 1617 images from two other hospitals were used for model external validation. Modeling learning based on WLI and NBI modalities was conducted using deep learning combined with a multi-instance learning approach (MIL). Furthermore, 50 prospectively collected videos were used to evaluate real-time model performance. A human-machine comparison involving 100 patients and 12 laryngologists assessed the real-world effectiveness of the model. RESULTS: The model achieved the highest area under the receiver operating characteristic curve (AUC) values of 0.868 and 0.884 in the internal and external validation sets, respectively. AUC in the video validation set was 0.825 (95% CI: 0.704-0.946). In the human-machine comparison, AI significantly improved AUC and accuracy for all laryngologists (p < 0.05). With the assistance of AI, the diagnostic abilities and consistency of all laryngologists improved. CONCLUSIONS: Our multicenter study developed an effective AI model using MIL and fusion of WLI and NBI images for VFL diagnosis, particularly aiding junior laryngologists. However, further optimization and validation are necessary to fully assess its potential impact in clinical settings. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Hydrophobic SiO2 Armor: Stabilizing Cuδ+ to Enhance CO2 Electroreduction toward C2+ Products in Strong Acidic Environments.

Electroreduction of CO2 in highly acidic environments holds promise for enhancing CO2 utilization efficiency. Due to the HER interference and structural instability, however, challenges in improving the selectivity and stability toward multicarbon (C2+) products remain. In this study, we proposed an "armor protection" strategy involving the deposition of ultrathin, hydrophobic SiO2 onto the Cu surface (Cu/SiO2) through a simple one-step hydrolysis. Our results confirmed the effective inhibition of HER by a hydrophobic SiO2 layer, leading to a high Faradaic efficiency (FE) of up to 76.9% for C2+ products at a current density of 900 mA cm-2 under a strongly acidic condition with a pH of 1. The observed high performance surpassed the reported performance for most previously studied Cu-based catalysts in acidic CO2RR systems. Furthermore, the ultrathin hydrophobic SiO2 shell was demonstrated to effectively prevent the structural reconstruction of Cu and preserve the oxidation state of Cuδ+ active sites during CO2RR. Additionally, it hindered the accumulation of K+ ions on the catalyst surface and diffusion of in situ generated OH- ions away from the electrode, thereby favoring C2+ product generation. In situ Raman analyses coupled with DFT simulations further elucidated that the SiO2 shell proficiently modulated *CO adsorption behavior on the Cu/SiO2 catalyst by reducing *CO adsorption energy, facilitating the C-C coupling. This work offers a compelling strategy for rationally designing and exploiting highly stable and active Cu-based catalysts for CO2RR in highly acidic environments.

Revealing molecular and cellular heterogeneity in hypopharyngeal carcinogenesis through single-cell RNA and TCR/BCR sequencing.

Introduction: Hypopharyngeal squamous cell carcinoma (HSCC) is one of the malignant tumors with the worst prognosis in head and neck cancers. The transformation from normal tissue through low-grade and high-grade intraepithelial neoplasia to cancerous tissue in HSCC is typically viewed as a progressive pathological sequence typical of tumorigenesis. Nonetheless, the alterations in diverse cell clusters within the tissue microenvironment (TME) throughout tumorigenesis and their impact on the development of HSCC are yet to be fully understood. Methods: We employed single-cell RNA sequencing and TCR/BCR sequencing to sequence 60,854 cells from nine tissue samples representing different stages during the progression of HSCC. This allowed us to construct dynamic transcriptomic maps of cells in diverse TME across various disease stages, and experimentally validated the key molecules within it. Results: We delineated the heterogeneity among tumor cells, immune cells (including T cells, B cells, and myeloid cells), and stromal cells (such as fibroblasts and endothelial cells) during the tumorigenesis of HSCC. We uncovered the alterations in function and state of distinct cell clusters at different stages of tumor development and identified specific clusters closely associated with the tumorigenesis of HSCC. Consequently, we discovered molecules like MAGEA3 and MMP3, pivotal for the diagnosis and treatment of HSCC. Discussion: Our research sheds light on the dynamic alterations within the TME during the tumorigenesis of HSCC, which will help to understand its mechanism of canceration, identify early diagnostic markers, and discover new therapeutic targets.

Multi-instance learning based artificial intelligence model to assist vocal fold leukoplakia diagnosis: A multicentre diagnostic study.

OBJECTIVE: To develop a multi-instance learning (MIL) based artificial intelligence (AI)-assisted diagnosis models by using laryngoscopic images to differentiate benign and malignant vocal fold leukoplakia (VFL). METHODS: The AI system was developed, trained and validated on 5362 images of 551 patients from three hospitals. Automated regions of interest (ROI) segmentation algorithm was utilized to construct image-level features. MIL was used to fusion image level results to patient level features, then the extracted features were modeled by seven machine learning algorithms. Finally, we evaluated the image level and patient level results. Additionally, 50 videos of VFL were prospectively gathered to assess the system's real-time diagnostic capabilities. A human-machine comparison database was also constructed to compare the diagnostic performance of otolaryngologists with and without AI assistance. RESULTS: In internal and external validation sets, the maximum area under the curve (AUC) for image level segmentation models was 0.775 (95 % CI 0.740-0.811) and 0.720 (95 % CI 0.684-0.756), respectively. Utilizing a MIL-based fusion strategy, the AUC at the patient level increased to 0.869 (95 % CI 0.798-0.940) and 0.851 (95 % CI 0.756-0.945). For real-time video diagnosis, the maximum AUC at the patient level reached 0.850 (95 % CI, 0.743-0.957). With AI assistance, the AUC improved from 0.720 (95 % CI 0.682-0.755) to 0.808 (95 % CI 0.775-0.839) for senior otolaryngologists and from 0.647 (95 % CI 0.608-0.686) to 0.807 (95 % CI 0.773-0.837) for junior otolaryngologists. CONCLUSIONS: The MIL based AI-assisted diagnosis system can significantly improve the diagnostic performance of otolaryngologists for VFL and help to make proper clinical decisions.

A 3D-printable gelatin/alginate/ε-poly-l-lysine hydrogel scaffold to enable porcine muscle stem cells expansion and differentiation for cultured meat development.

The mass proliferation of seed cells and imitation of meat structures remain challenging for cell-cultured meat production. With excellent biocompatibility, high water content and porosity, hydrogels are frequently-studied materials for anchorage-dependent cell scaffolds in biotechnology applications. Herein, a scaffold based on gelatin/alginate/ε-Poly-l-lysine (GAL) hydrogel is developed for skeletal muscle cells, which has a great prospect in cell-cultured meat production. In this work, the hydrogel GAL-4:1, composed of gelatin (5 %, w/v), alginate (5 %, w/v) and ε-Poly-l-lysine (molar ratio vs. alginate: 4:1) is selected as cell scaffold based on Young's modulus of 11.29 ± 1.94 kPa, satisfactory shear-thinning property and suitable porous organized structure. The commercially available C2C12 mouse skeletal myoblasts and porcine muscle stem cells (PMuSCs), are cultured in the 3D-printed scaffold. The cells show strong ability of attachment, proliferation and differentiation after induction, showing high biocompatibility. Furthermore, the cellular bioprinting is performed with GAL-4:1 hydrogel and freshly extracted PMuSCs. The extracted PMuSCs exhibit high viability and display early myogenesis (desmin) on the 3D scaffold, suggesting the great potential of GAL hydrogel as 3D cellular constructs scaffolds. Overall, we develop a novel GAL hydrogel as a 3D-printed bioactive platform for cultured meat research.

Continuous and low-carbon production of biomass flash graphene.

Flash Joule heating (FJH) is an emerging and profitable technology for converting inexhaustible biomass into flash graphene (FG). However, it is challenging to produce biomass FG continuously due to the lack of an integrated device. Furthermore, the high-carbon footprint induced by both excessive energy allocation for massive pyrolytic volatiles release and carbon black utilization in alternating current-FJH (AC-FJH) reaction exacerbates this challenge. Here, we create an integrated automatic system with energy requirement-oriented allocation to achieve continuous biomass FG production with a much lower carbon footprint. The programmable logic controller flexibly coordinated the FJH modular components to realize the turnover of biomass FG production. Furthermore, we propose pyrolysis-FJH nexus to achieve biomass FG production. Initially, we utilize pyrolysis to release biomass pyrolytic volatiles, and subsequently carry out the FJH reaction to focus on optimizing the FG structure. Importantly, biochar with appropriate resistance is self-sufficient to initiate the FJH reaction. Accordingly, the medium-temperature biochar-based FG production without carbon black utilization exhibited low carbon emission (1.9 g CO2-eq g-1 graphene), equivalent to a reduction of up to ~86.1% compared to biomass-based FG production. Undoubtedly, this integrated automatic system assisted by pyrolysis-FJH nexus can facilitate biomass FG into a broad spectrum of applications.

Jasmonates Promote ß-Amylase-Mediated Starch Degradation to Confer Cold Tolerance in Tomato Plants.

Cold stress severely restricts growth and development, reduces yields, and impairs quality in tomatoes (Solanum lycopersicum). Amylase-associated starch degradation and soluble sugar accumulation have been implicated in adaptation and resistance to abiotic stress. Here, we report a ß-amylase (BAM) gene, SlBAM3, which plays a central role in tomato cold tolerance. The expression of SlBAM3 was triggered by cold stress. SlBAM3 knockout using the CRISPR/Cas9 system retarded starch degradation and reduced soluble sugar accumulation in tomato plants, eventually attenuating cold tolerance. Expression analysis revealed that the SlBAM3 transcript level was boosted by MeJA. Furthermore, MYC2, an essential component of the JA signaling pathway, could bind to the SlBAM3 promoter and directly activate SlBAM3 transcription, as revealed by yeast one-hybrid and dual LUC assays. In addition, the suppression of MYC2 resulted in increased starch accumulation, decreased soluble sugar content, and reduced tolerance to cold stress in tomato plants. Taken together, these findings demonstrate that JA positively regulates ß-amylase-associated starch degradation through the MYC2-SlBAM3 module in tomato during cold stress. The results of the present work expand our understanding of the mechanisms underlying BAM gene activation and starch catabolism under cold stress. The regulatory module of SlBAM3 can be further utilized to breed tomato cultivars with enhanced cold tolerance.

MXene-based composite aerogels with bifunctional ferrous ions for the efficient degradation of phenol from wastewater.

Herein, MXene-based composite aerogel (MXene-Fe2+ aerogel) are constructed by a one-step freeze-drying method, using Ti3C2Tx MXene layers as substrate material and ferrous ion (Fe2+) as crosslinking agent. With the aid of the Fe2+ induced Fenton reaction, the synthesized aerogels are used as the particle electrodes to remove phenol from wastewater with three-dimensional electrode technology. Combined with the dual roles of Fe2+ and the highly conductive MXene, the obtained particle electrode possesses extremely effective phenol degradation. The effects of experiment parameters such as Fe2+ to MXene ratio, particle electrode dosage, applied voltage, and initial pH of solution on the removal of phenol are discussed. At pH = 2.5, phenol with 50 mg/L of initial concentration can be completely removed within 50 min at 10 V with the particle electrode dosage of 0.56 g/L. Finally, the mechanism of degradation is explored. This work provides an effective way for phenol degradation by MXene-based aerogel, which has great potential for the degradation of other organic pollutants in wastewater.

Survival and neurological function in patients treated with extracorporeal membrane oxygenation and therapeutic hypothermia: a protocol for updating a systematic review.

INTRODUCTION: The widespread application of extracorporeal membrane oxygenation (ECMO) has enhanced clinical outcomes for patients experiencing cardiac arrest. However, its effectiveness is still limited and falls short of the desired level. Therapeutic hypothermia, which maintains body temperatures between 32°C and 36°C in cardiac arrest patients treated with ECMO, has been proposed as a potential means of neuroprotection and increased survival rates. Nevertheless, it remains controversial, and its impact on patient complications has yet to be fully understood. Thus, this paper aims to update the protocol for a systematic review of patients treated with ECMO and therapeutic hypothermia, in order to explore its effects on survival and neurological function. METHOD AND ANALYSIS: This protocol has been developed in compliance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols 2015. The following databases will be systematically searched: PubMed, Web of Science, Cochrane Library, Embase, Ovid, CNKI, Wanfang and China Biology Medicine Disc. The database search strategy will use a combination of subject terms and free-text keywords. The search will encompass articles from the inception of each database up to 15 June 2023. Inclusion criteria encompass randomised controlled trials, cohort studies, case-control studies and quasi-experimental studies. Two researchers will independently review articles and extract relevant data based on these criteria. Any disagreements will be resolved through discussion. Data analysis will be performed using Review Manager software. ETHICS AND DISSEMINATION: Since no patient data were collected in this study, ethical approval was not required. Research findings will be released in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023435353.

Fabrication of a Coculture Organoid Model in the Biomimetic Matrix of Alginate to Investigate Breast Cancer Progression in a TAMs-Leading Immune Microenvironment.

The current research models of breast cancer are usually limited in their capacity to recapitulate the tumor microenvironment in vitro. The lack of an extracellular matrix (ECM) oversimplifies cell-cell or cell-ECM cross-talks. Moreover, the lack of tumor-associated macrophages (TAMs), that can comprise up to 50% of some solid neoplasms, poses a major problem for recognizing various hallmarks of cancer. To address these concerns, a type of direct breast cancer cells (BCCs)-TAMs coculture organoid model was well developed by a sequential culture method in this study. Alginate cryogels were fabricated with appropriate physical and mechanical properties to serve as an alternative ECM. Then, our previous experience was leveraged to polarize TAMs inside of the cryogels for creating an in vitro immune microenvironment. The direct coculture significantly enhanced BCCs organoid growth and cancer aggressive phenotypes, including the stemness, migration, ECM remodeling, and cytokine secretion. Furthermore, transcriptomic analysis and protein-protein interaction networks implied certain pathways (PI3K-Akt pathway, MAPK signaling pathway, etc.) and targets (TNF, PPARG, TLR2, etc.) during breast cancer progression in a TAM-leading immune microenvironment. Future studies to advance treatment strategies for BCC patients may benefit from using this facile model to reveal and target the interactions between cancer signaling and the immune microenvironment.