Identification and Validation of a Prognostic Signature Based on Fibroblast Immune-related Genes to Predict the Prognosis and Therapeutic Response of renal clear cell carcinoma by Integrated Analysis of Single-Cell and Bulk RNA Sequencing Data.

Background: The importance of fibroblasts in cancer progression is becoming more acknowledged, particularly the significance of their immune-related genes. However, the precise roles these genes play in fibroblasts throughout tumor development remains unclear. Exploring how these genes function in advancing kidney renal clear cell carcinoma (KIRC) could provide answers to these uncertainties. Material and method: The Cancer Genome Atlas (TCGA) database served as the source of data for KIRC patients. We distinguished fibroblast immune-related genes (FIGs), which are used to construct risk score. Further analysis conducted including enrichment analysis, assessment of tumor mutation burden (TMB), evaluation of tumor microenvironment (TME), analysis of immune cell infiltration, and drug sensitivity prediction. Result: The risk score using 6 FIGs effectively predicts the outcomes for KIRC patients. Nomogram which is based on the risk score and clinical data, demonstrated superior predictive performance compared to the version without the risk score. Enrichment analysis identified that coagulation pathway predominates in high-risk group, the protein secretion pathway is prevalent in low-risk patients' cohort. The adverse prognosis in high-risk patient cohort could be linked to an elevated TMB. TME analysis showed that high-risk group's tumor tissues contain more immune and stromal cells. Furthermore, the amount of regulatory T cells increases with the risk score. Low-risk group response better to immunotherapy. Finally, RT-qPCR confirmed the differential expression of FIGs in KIRC patients. Conclusion: This risk score and nomogram are valuable tools assessing KIRC patients' prognosis. Poorer prognosis in high-risk categories may have relationship with activation of coagulation pathway and a higher TMB.

Decrypting Synergy of Alloy & Metal Nanoparticles Within Nitrogen-Doped Carbon Nanosheets for Zn-Air Batteries with Ultralong Cycling Stability.

The exploration of efficient, robust, and low-cost bifunctional electrocatalysts to drive the commercial application of Zn-air batteries (ZABs) is of great significance but still remains a challenge. Herein, a 1D coordination polymer (1D-CP) derived FeNi alloy & Co nanoparticles (NPs) co-implanted N-doped carbon nanosheets (FNC/NCS) is judiciously crafted and employed as a high-performance electrocatalyst for ultralong lifetime ZABs. The key to this strategy is the leveraging of metal-coordinated melamine to direct the pyrolysis of 1D-CP, enabling the in situ formation of well-dispersed FeNi alloy and Co NPs within the carbon matrix. The resulting FNC/NCS exhibits prominent oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) activity with a small overall oxygen potential difference (ΔE = 0.68 V). Density functional theory (DFT) simulation demonstrates that the synergistic effect between FeNi alloy and Co NPs can reduce energy barriers, promote electron transfer, and optimize the formation of crucial intermediates, thereby largely boost ORR/OER activity of FNC/NCS. The FNC/NCS-assembled ZABs possess high specific capacity, large power density, and ultralong cycling life in both aqueous (> 3300 h) and solid-state (150 h) electrolytes. This work provides a viable strategy for 1D-CP-derived bifunctional electrocatalysts and dissects the synergistic effect between different metal species, affording significant guidance for the development of renewable energy materials.

Downregulation of chemokine (C­C motif) ligand 5 induced by a novel 8­hydroxyquinoline derivative (91b1) suppresses tumor invasiveness in esophageal carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a particularly aggressive form of cancer with high mortality. In the present study, a novel 8­hydroxyquinoline derivative (91b1) was investigated for its anticancer activities in ESCC along with its associated mechanisms. The in vitro cytotoxic effect of 91b1 were evaluated across five ESCC cell lines using MTS assay, with cisplatin serving as a comparative standard. Changes in gene expression profile were identified by cDNA microarray and further validated by qualitative PCR and immunostaining. Additionally, protein levels of the most notably downregulated target in archival ESCC samples were also studied. 91b1 demonstrated comparable anticancer effect with cisplatin. Notably, chemokine ligand 5 (Ccl5) was identified as the most substantially downregulated gene, with its suppression at both mRNA and protein expression in ESCC cells, exhibiting a dose­dependent manner. The recombinant human protein of CCL5 enhanced the invasion of ESCC cells using the Transwell assay. The upregulation of CCL5 protein was also detected in 50% of ESCC cell lines. CCL5 was also overexpressed in 76.9% of ESCC specimens. The overall results indicated that 91b1 could effectively induce anticancer effect on ESCC cells through downregulating CCL5 expression with suppression of tumor invasion. Overall, these findings suggested that 91b1 effectively inhibited ESCC cell proliferation and tumor invasion by downregulating CCL5 expression, highlighting its potential as a therapeutic agent for ESCC treatment.

Effectiveness of Compound Dilong Capsules in Patients with Asymptomatic Cerebral Carotid Artery Stenosis: A Retrospective Case-Control Study.

Purpose: Asymptomatic cerebral carotid artery stenosis (ACCAS) benefits from secondary prevention via statins and antiplatelets; nonetheless, the impact of medication alone is often limited. Evidence has suggested enhanced therapeutic outcomes when Chinese patent medicine-specifically, compound dilong capsules (CDC)-is integrated with conventional secondary prevention measures. Patients and Methods: We retrospectively analyzed 319 ACCAS patients from January 2018 to December 2022 at Xuanwu Hospital, Capital Medical University. Depending on the clinical outcomes-improvement or stabilization versus progression-patients were classified into effective or ineffective treatment groups. Patient medical records and questionnaire responses were the primary data sources. The study accounted for demographic variables, clinical history, and medication details, with the primary focus on CDC use and its duration. Treatment outcomes were gauged alongside Transcranial color-coded sonography and Carotid Doppler ultrasonography findings. We employed both univariate and multivariate statistical methods to assess the data. Results: CDC administration (aOR=2.51, 95% CI 1.39-4.54, P=0.002) and extended usage beyond six months (aOR=3.54, 95% CI 1.71-7.32, P=0.001) demonstrate a statistically significant correlation with treatment efficacy. Gender (aOR=2.54, 95% CI 1.30-5.00, P=0.007), hypertension management (aOR=0.56, 95% CI 0.33-0.95, P=0.031), and antiplatelet therapy with aspirin (aOR=9.53, 95% CI 1.15-78.89, P=0.037) or clopidogrel (aOR=9.97, 95% CI 1.10-90.12, P=0.041) also influenced the therapeutic outcome significantly. Conclusion: Incorporating CDC as part of a secondary prevention strategy for over six months can beneficially modulate and limit the progression of vascular stenosis in ACCAS. These findings underscore the value of combining traditional Chinese medicine with modern pharmacological interventions in ACCAS management.

Fe3O4@R837 Nanoplatform Enhances Chemical Dynamic Therapy and Immunotherapy: Integrated Transcriptomic Analysis Reveals Key Genes in Breast Cancer Prognosis.

Breast cancer represents a substantial contributor to mortality rates among women with cancer. Chemical dynamic therapy is a promising anticancer strategy that utilizes the Fenton reaction to transform naturally occurring hydrogen peroxide (H2O2) into hydroxyl radicals (•OH). Additionally, cancer immunotherapy using immune drugs, such as imiquimod (R837), has shown promise in activating T cells to kill tumor cells. In this study, we proposed a Fe3O4@R837 smart nanoplatform that can trigger the Fenton reaction and induce immune responses in breast cancer treatment. Furthermore, we performed transcriptome sequencing on breast cancer samples and used the R package (limma) to analyze differential expression profiles and select differentially expressed genes (DEGs). We obtained clinical information and RNA expression matrix data from The Cancer Genome Atlas database to perform survival analysis and identify prognostic-related genes (PRGs) and molecular subtypes with distinct prognoses. We used the TIMER 2.0 web and other methods to determine the tumor immune microenvironment and immune status of different prognostic subtypes. We identified DPGs by taking the intersection of DEGs and PRGs and performed functional analyses, including gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, to elucidate potential mechanisms. Subsequently, we constructed a protein-protein interaction network using the STRING database to visualize the interactions between the DPGs. We screened hub genes from the DPGs using the Cytoscape plugin and identified six hub genes: CD3E, GZMK, CD27, SH2D1A, ZAP70, and TIGIT. Our results indicate that these six key genes regulate immune cell recruitment to increase T-cell cytotoxicity and kill tumors. Targeting these key genes can enhance immunotherapy and improve the breast cancer prognosis.

Incorporating machine learning and PPI networks to identify mitochondrial fission-related immune markers in abdominal aortic aneurysms.

Purpose: The aim of this study is to investigate abdominal aortic aneurysm (AAA), a disease characterised by inflammation and progressive vasodilatation, for novel gene-targeted therapeutic loci. Methods: To do this, we used weighted co-expression network analysis (WGCNA) and differential gene analysis on samples from the GEO database. Additionally, we carried out enrichment analysis and determined that the blue module was of interest. Additionally, we performed an investigation of immune infiltration and discovered genes linked to immune evasion and mitochondrial fission. In order to screen for feature genes, we used two PPI network gene selection methods and five machine learning methods. This allowed us to identify the most featrue genes (MFGs). The expression of the MFGs in various cell subgroups was then evaluated by analysis of single cell samples from AAA. Additionally, we looked at the expression levels of the MFGs as well as the levels of inflammatory immune-related markers in cellular and animal models of AAA. Finally, we predicted potential drugs that could be targeted for the treatment of AAA. Results: Our research identified 1249 up-regulated differential genes and 3653 down-regulated differential genes. Through WGCNA, we also discovered 44 genes in the blue module. By taking the point where several strategies for gene selection overlap, the MFG (ITGAL and SELL) was produced. We discovered through single cell research that the MFG were specifically expressed in T regulatory cells, NK cells, B lineage, and lymphocytes. In both animal and cellular models of AAA, the MFGs' mRNA levels rose. Conclusion: We searched for the AAA novel targeted gene (ITGAL and SELL), which most likely function through lymphocytes of the B lineage, NK cells, T regulatory cells, and B lineage. This analysis gave AAA a brand-new goal to treat or prevent the disease.

Isorhamnetin Alleviates Mitochondrial Injury in Severe Acute Pancreatitis via Modulation of KDM5B/HtrA2 Signaling Pathway.

Severe acute pancreatitis (SAP), a widespread inflammatory condition impacting the abdomen with a high mortality rate, poses challenges due to its unclear pathogenesis and the absence of effective treatment options. Isorhamnetin (ISO), a naturally occurring flavonoid, demonstrates robust antioxidant and anti-inflammatory properties intricately linked to the modulation of mitochondrial function. However, the specific protective impact of ISO on SAP remains to be fully elucidated. In this study, we demonstrated that ISO treatment significantly alleviated pancreatic damage and reduced serum lipase and amylase levels in the mouse model of SAP induced by sodium taurocholate (STC) or L-arginine. Utilizing an in vitro SAP cell model, we found that ISO co-administration markedly prevented STC-induced pancreatic acinar cell necrosis, primarily by inhibiting mitochondrial ROS generation, preserving ATP production, maintaining mitochondrial membrane potential, and preventing the oxidative damage and release of mitochondrial DNA. Mechanistically, our investigation identified that high-temperature requirement A2 (HtrA2) may play a central regulatory role in mediating the protective effect of ISO on mitochondrial dysfunction in STC-injured acinar cells. Furthermore, through an integrated approach involving bioinformatics analysis, molecular docking analysis, and experimental validation, we uncovered that ISO may directly impede the histone demethylation activity of KDM5B, leading to the restoration of pancreatic HtrA2 expression and thereby preserving mitochondrial function in pancreatic acinar cells following STC treatment. In conclusion, this study not only sheds new light on the intricate molecular complexities associated with mitochondrial dysfunction during the progression of SAP but also underscores the promising value of ISO as a natural therapeutic option for SAP.

Zn-based batteries for sustainable energy storage: strategies and mechanisms.

Batteries play a pivotal role in various electrochemical energy storage systems, functioning as essential components to enhance energy utilization efficiency and expedite the realization of energy and environmental sustainability. Zn-based batteries have attracted increasing attention as a promising alternative to lithium-ion batteries owing to their cost effectiveness, enhanced intrinsic safety, and favorable electrochemical performance. In this context, substantial endeavors have been dedicated to crafting and advancing high-performance Zn-based batteries. However, some challenges, including limited discharging capacity, low operating voltage, low energy density, short cycle life, and complicated energy storage mechanism, need to be addressed in order to render large-scale practical applications. In this review, we comprehensively present recent advances in designing high-performance Zn-based batteries and in elucidating energy storage mechanisms. First, various redox mechanisms in Zn-based batteries are systematically summarized, including insertion-type, conversion-type, coordination-type, and catalysis-type mechanisms. Subsequently, the design strategies aiming at enhancing the electrochemical performance of Zn-based batteries are underscored, focusing on several aspects, including output voltage, capacity, energy density, and cycle life. Finally, challenges and future prospects of Zn-based batteries are discussed.

Recent Advances in Environmentally Friendly Dual-crosslinking Polymer Networks.

Environmentally friendly crosslinked polymer networks feature degradable covalent or non-covalent bonds, with many of them manifesting dynamic characteristics. These attributes enable convenient degradation, facile reprocessibility, and self-healing capabilities. However, the inherent instability of these crosslinking bonds often compromises the mechanical properties of polymer networks, limiting their practical applications. In this context, environmentally friendly dual-crosslinking polymer networks (denoted EF-DCPNs) have emerged as promising alternatives to address this challenge. These materials effectively balance the need for high mechanical properties with the ability to degrade, recycle, and/or self-heal. Despite their promising potential, investigations into EF-DCPNs remain in their nascent stages, and several gaps and limitations persist. This Review provides a comprehensive overview of the synthesis, properties, and applications of recent progress in EF-DCPNs. Firstly, synthetic routes to a rich variety of EF-DCPNs possessing two distinct types of dynamic bonds (i.e., imine, disulfide, ester, hydrogen bond, coordination bond, and other bonds) are introduced. Subsequently, complex structure- and dynamic nature-dependent mechanical, thermal, and electrical properties of EF-DCPNs are discussed, followed by their exemplary applications in electronics and biotechnology. Finally, future research directions in this rapidly evolving field are outlined.

Layered S-Bridged Covalent Triazine Frameworks via a Bifunctional Template-Catalytic Strategy Enabling High-Performance Zinc-Ion Hybrid Supercapacitors.

Exploring covalent triazine frameworks (CTFs) with high capacitative activity is highly desirable and challenging. Herein, the S-rich CTFs cathode is pioneeringly introduced in Zn-ion hybrid supercapacitors (ZSC), achieving outstanding capacity and energy density, and satisfactory anti-freezing flexibility. Specifically, the S-bridged CTFs are synthesized by a bifunctional template-catalytic strategy, where ZnCl2 serves as both the catalyst/solvent and in situ template to construct triazine frameworks with interconnected pores and layered gaps. The resultant CTFs (CTFS-750) are employed as a reasonable pattern-like system to more deeply scrutinize the synergistic effect of S-bridged triazine and layered porous architecture for polymer-based cathodes in Zn-ion storage. The experimental results indicate that the adsorption barriers of Zn-ions on CTFS-750 are effectively weakened, and accessible Zn2+-absorption sites provided by the C─S─C and C═N bonds have been confirmed via DFT calculations. Consequently, the CTFS-750 cathode-assembled ZSC displays an ultra-high capacity of 211.6 mAh g-1 at 1.0 A g-1, an outstanding energy density of 202.7 Wh kg-1, and attractive cycling performance. Moreover, the resulting flexible ZSC device shows superior capacity, good adaptability, and satisfactory anti-freezing behavior. This approach sheds new light on constructing advanced polymer-based cathodes at the atom level and paves the way for fabricating high-performance ZSC and beyond.

Application of improved GalNAc conjugation in development of cost-effective siRNA therapies targeting cardiovascular diseases.

N-Acetylgalactosamine (GalNAc)-conjugated small interfering RNA (siRNA) therapies have received approval for treating both orphan and prevalent diseases. To improve in vivo efficacy and streamline the chemical synthesis process for efficient and cost-effective manufacturing, we conducted this study to identify better designs of GalNAc-siRNA conjugates for therapeutic development. Here, we present data on redesigned GalNAc-based ligands conjugated with siRNAs against angiopoietin-like 3 (ANGPTL3) and lipoprotein (a) (Lp(a)), two target molecules with the potential to address large unmet medical needs in atherosclerotic cardiovascular diseases. By attaching a novel pyran-derived scaffold to serial monovalent GalNAc units before solid-phase oligonucleotide synthesis, we achieved increased GalNAc-siRNA production efficiency with fewer synthesis steps compared to the standard triantennary GalNAc construct L96. The improved GalNAc-siRNA conjugates demonstrated equivalent or superior in vivo efficacy compared to triantennary GalNAc-conjugated siRNAs.

Ammonium Folate-Reinforced Self-Assembly of Gelatin into N/B/O-Enriched Hierarchical Porous Carbons with Loosely Layered Structure for Anti-Freezing Flexible Supercapacitors.

Heteroatom-doped layered porous carbons are recently regarded as promising electrode materials for high energy density supercapacitors because they can integrate high-level heteroatom-doping and layered nano-space together to provide huge pseudocapacitive reaction areas and accelerate ion diffusion/transport. Herein, an innovative strategy is reported to prepare N/B/O co-doped layered porous carbons via ammonium folate-reinforced self-assembly of gelatin and boric acid followed by carbonization. Biomass-derived ammonium folate not only acts as an N-riched precursor but also can fasten in the process of self-assembly via boric acid-assisted electrostatic adsorption and hydrogen bonding to promote the formation of stable 3D cross-linked networks, resulting in the obtained N/B/O co-doped layered porous carbon (BNLC-850) has a large specific surface area (1822 m2 g-1 ), hierarchical porous structure and super-high heteroatom contents (N, 12.65; B, 5.67; and O, 13.84 at.%). The BNLC-850 achieves an ultrahigh specific capacitance of 525.2 F g-1 in the alkaline electrolyte at 0.5 A g-1 , meanwhile, DFT calculations reveal that the high-level N/B/O-doping can effectively weaken the adsorption barriers of K-ions. Moreover, the BNLC-850 assembles anti-freezing flexible solid-state supercapacitors in MPEI-TF-IL gel polymer electrolyte deliver a high energy density of 41.2 Wh kg-1 , excellent flexibility, and long cycle-life at -20 °C.

N-Coordinated Iridium-Molybdenum Dual-Atom Catalysts Enabling Efficient Bifunctional Hydrogen Electrocatalysis.

Achieving effective hydrogen evolution/oxidation reaction (HER/HOR) across a wide pH span is of critical importance in unlocking the full potential of hydrogen energy but remains intrinsically challenging. Here, we engineer the N-coordinated Ir-Mo dual atoms on a carbon matrix by ultrafast high-temperature sintering, creating an efficient bifunctional electrocatalyst for both HER and HOR in both acidic and alkaline electrolytes. The optimized catalyst, Ir-Mo DAC/NC, demonstrates exceptional performance, with a significantly reduced HER overpotential of 11.3 mV at 10 mA/cm2 and a HOR exchange current (i0,m) of 3972 mA/mgIr in acidic conditions, surpassing the performance of Pt/C and Ir/C catalysts. In alkaline conditions, Ir-Mo DAC/NC also outperforms Pt/C, as evidenced by its low HER overpotential of 23 mV at 10 mA/cm2 and a high i0,m of 1308 mA/mgIr. Furthermore, our catalyst exhibits remarkable stability in both acidic and alkaline environments. DFT calculations results reveal that the superior electrochemical performance of Ir-Mo DAC/NC arises from the electronic synergy between Ir and Mo pairs, which regulates the interaction between the intermediates and active sites. These findings present a promising strategy for the development of dual-atom catalysts (DACs), with potential applications in the polymer fuel cells and water electrolyzers.

Muscone inhibits angiotensin II-induced cardiac hypertrophy through the STAT3, MAPK and TGF-ß/SMAD signaling pathways.

BACKGROUND: Muscone is a chemical monomer derived from musk. Although many studies have confirmed the cardioprotective effects of muscone, the effects of muscone on cardiac hypertrophy and its potential mechanisms are unclear.The aim of the present study was to investigate the effect of muscone on angiotensin (Ang) II-induced cardiac hypertrophy. METHODS AND RESULTS: In the present study, we found for the first time that muscone exerted inhibitory effects on Ang II-induced cardiac hypertrophy and cardiac injury in mice. Cardiac function was analyzed by echocardiography measurement, and the degree of cardiac fibrosis was determined by the quantitative real-time polymerase chain reaction (qRT-PCR), Masson trichrome staining and western blot assay. Secondly, qRT-PCR experiment showed that muscone attenuated cardiac injury by reducing the secretion of pro-inflammatory cytokines and promoting the secretion of anti-inflammatory cytokines. Moreover, western blot analysis found that muscone exerted cardio-protective effects by inhibiting phosphorylation of key proteins in the STAT3, MAPK and TGF-ß/SMAD pathways. In addition, CCK-8 and determination of serum biochemical indexes showed that no significant toxicity or side effects of muscone on normal cells and organs. CONCLUSIONS: Muscone could attenuate Ang II-induced cardiac hypertrophy, in part, by inhibiting the STAT3, MAPK, and TGF-ß/SMAD signaling pathways.

"Setaria viridis"-like cobalt complex derived Co/N-doped carbon nanotubes as efficient ORR/OER electrocatalysts for long-life rechargeable Zn-air batteries.

The development of efficient and facile strategies to prepare metal and nitrogen codoped carbon (M-N-C) materials as oxygen electrocatalysts in rechargeable Zn-air batteries with high performance and a long life is challenging. Herein, we report a simple route to synthesize cobalt and nitrogen codoped carbon nanotubes (denoted as Co/N-CNT) as bifunctional oxygen electrocatalysts for rechargeable Zn-air batteries (ZABs). The Co/N-CNT are fabricated through the surface modification of carbon nanotubes with cobalt salt and melamine followed by pyrolysis, which delivers outstanding oxygen reduction/evolution reaction (ORR/OER) activity with a low overall potential gap (ΔE = 0.77 V) and remarkable durability. The home-made Zn-air batteries exhibit a high power density (130 mW cm-2vs. 82 mW cm-2), a large specific capacity of (864 mA h g-1Znvs. 785 mA h g-1Zn), and a long cycling life (1200 h vs. 60 h) in both aqueous and solid media. This work opens an avenue for the reasonable surface modification of carbon nanotubes with various metals and heteroatoms to achieve high-performance electrocatalysts for clean and sustainable energy conversion and storage devices.

Corrigendum: Shu-Xie decoction alleviates oxidative stress and colon injury in acute sleep-deprived mice by suppressing p62/KEAP1/NRF2/HO1/NQO1 signaling.

[This corrects the article DOI: 10.3389/fphar.2023.1107507.].

α-Stereoselective 3-Deoxy-d-manno-oct-2-ulosonoic Acid (Kdo) O-Glycosylation with a p-Toluenethioglycoside Donor by the (p-Tol)2SO/Tf2O Preactivation Strategy.

A convenient and efficient approach was developed to synthesize α-Kdo O-glycosides based on the Tf2O/(p-Tol)2SO preactivation strategy using peracetylated Kdo thioglycoside as a donor. Under the optimized reaction conditions, several O-glycoside products, including α-(2 → 1)-, α-(2 → 2)-, α-(2 → 3)-, and α-(2 → 6)-Kdo products, were stereoselectively synthesized in high yields. Remarkably, a series of aromatic α-Kdo O-glycosides were first and successfully constructed in high yields. An SN2-like mechanism was revealed by DFT calculations and experimental results.

Shu-Xie decoction alleviates oxidative stress and colon injury in acute sleep-deprived mice by suppressing p62/KEAP1/NRF2/HO1/NQO1 signaling.

Introduction: Sleep disorders are common clinical psychosomatic disorders that can co-exist with a variety of conditions. In humans and animal models, sleep deprivation (SD) is closely related with gastrointestinal diseases. Shu-Xie Decoction (SX) is a traditional Chinese medicine (TCM) with anti-nociceptive, anti-inflammatory, and antidepressant properties. SX is effective in the clinic for treating patients with abnormal sleep and/or gastrointestinal disorders, but the underlying mechanisms are not known. This study investigated the mechanisms by which SX alleviates SD-induced colon injury in vivo. Methods: C57BL/6 mice were placed on an automated sleep deprivation system for 72 h to generate an acute sleep deprivation (ASD) model, and low-dose SX (SXL), high-dose SX (SXH), or S-zopiclone (S-z) as a positive control using the oral gavage were given during the whole ASD-induced period for one time each day. The colon length was measured and the colon morphology was visualized using hematoxylin and eosin (H&E) staining. ROS and the redox biomarkers include reduced glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) were detected. Quantitative real-time PCR (qRT-PCR), molecular docking, immunofluorescence and western blotting assays were performed to detect the antioxidant signaling pathways. Results: ASD significantly increased FBG levels, decreased colon length, moderately increased the infiltration of inflammatory cells in the colon mucosa, altered the colon mucosal structure, increased the levels of ROS, GSH, MDA, and SOD activity compared with the controls. These adverse effects were significantly alleviated by SX treatment. ASD induced nuclear translocation of NRF2 in the colon mucosal cells and increased the expression levels of p62, NQO1, and HO1 transcripts and proteins, but these effects were reversed by SX treatment. Conclusion: SX decoction ameliorated ASD-induced oxidative stress and colon injury by suppressing the p62/KEAP1/NRF2/HO1/NQO1 signaling pathway. In conclusion, combined clinical experience, SX may be a promising drug for sleep disorder combined with colitis.

Study on the impact of green finance on low carbon development of manufacturing industry from the perspective of multidimensional space: evidence from China.

In order to test the impact of green finance on the low-carbon development level of China's manufacturing industry, this paper takes green finance as an explanatory variable, and chooses the level of fixed asset investment in the manufacturing industry, the intensity of environmental regulations, the proportion of environmental pollution control investment, and the proportion of R&D investment as four control variables. Empirical tests are carried out on the four dependent variables, including manufacturing industry's low-carbon development level, added value growth rate, industrial structure upgrading level, and environmental protection status. The test results show that green finance is positively correlated with the low-carbon development of the manufacturing industry and the growth rate of added value, and inversely correlated with industrial structure upgrading and environmental protection; green finance supports dependent variables in the following order: low-carbon development > environmental protection > economic growth > industrial structure. It can be seen that the main role of green finance is to promote low-carbon development and environmental protection, but it is not the best tool to promote the growth rate of manufacturing industry and upgrade the level of industrial structure. In addition, due to the spillover effect of green finance in the process of promoting the development of the manufacturing industry, it is necessary to increase green financial investment in a long-term and sustained manner to gradually promote the low-carbon and sustainable development of China's manufacturing industry.

A draft genome of the medicinal plant Cremastra appendiculata (D. Don) provides insights into the colchicine biosynthetic pathway.

Cremastra appendiculata (D. Don) Makino is a rare terrestrial orchid with a high market value as an ornamental and Chinese traditional medicinal herb with a wide range of pharmacological properties. The pseudobulbs of C. appendiculata are one of the primary sources of the famous traditional Chinese medicine "Shancigu", which has been clinically used for treating many diseases, especially, as the main component to treat gout. The lack of genetic research and genome data restricts the modern development and clinical use of C. appendiculata. Here, we report a 2.3 Gb chromosome-level genome of C. appendiculata. We identify a series of candidates of 35 candidate genes responsible for colchicine biosynthesis, among which O-methyltransferase (OMT) gene exhibits an important role in colchicine biosynthesis. Co-expression analysis reveal purple and green-yellow module have close relationships with pseudobulb parts and comprise most of the colchicine pathway genes. Overall, our genome data and the candidate genes reported here set the foundation to decipher the colchicine biosynthesis pathways in medicinal plants.