Physiologically based pharmacokinetic modeling to predict the pharmacokinetics of codeine in different CYP2D6 phenotypes.

Objectives: Codeine, a prodrug used as an opioid agonist, is metabolized to the active product morphine by CYP2D6. This study aimed to establish physiologically based pharmacokinetic (PBPK) models of codeine and morphine and explore the influence of CYP2D6 genetic polymorphisms on the pharmacokinetics of codeine and morphine. Methods: An initial PBPK modeling of codeine in healthy adults was established using PK-Sim® software and subsequently extrapolated to CYP2D6 phenotype-related PBPK modeling based on the turnover frequency (Kcat) of CYP2D6 for different phenotype populations (UM, EM, IM, and PM). The mean fold error (MFE) and geometric mean fold error (GMFE) methods were used to compare the differences between the predicted and observed values of the pharmacokinetic parameters to evaluate the accuracy of PBPK modeling. The validated models were then used to support dose safety for different CYP2D6 phenotypes. Results: The developed and validated CYP2D6 phenotype-related PBPK model successfully predicted codeine and morphine dispositions in different CYP2D6 phenotypes. Compared with EMs, the predicted AUC0-∞ value of morphine was 98.6% lower in PMs, 60.84% lower in IMs, and 73.43% higher in UMs. Morphine plasma exposure in IMs administered 80 mg of codeine was roughly comparable to that in EMs administered 30 mg of codeine. CYP2D6 UMs may start dose titration to achieve an optimal individual regimen and avoid a single dose of over 20 mg. Codeine should not be used in PMs for pain relief, considering its insufficient efficacy. Conclusion: PBPK modeling can be applied to explore the dosing safety of codeine and can be helpful in predicting the effect of CYP2D6 genetic polymorphisms on drug-drug interactions (DDIs) with codeine in the future.

Comparative Analysis of the Gelsemium Alkaloids Metabolism in Human, Pig, Goat, and Rat Liver Microsomes.

AIM: The aim of this study was to investigate the metabolism of Gelsemium elegans in human, pig, goat and rat liver microsomes and to elucidate the metabolic pathways and cleavage patterns of the Gelsemium alkaloids among different species. METHODS: A human, goat, pig and rat liver microparticles were incubated in vitro. After incubating at 37°C for 1 hour and centrifuging, the processed samples were detected by HPLC/Qq-TOFMS was used to detect alcohol extract of Gelsemium elegans and its metabolites. RESULTS: Forty-six natural products were characterized from alcohol extract of Gelsemium elegans and 13 metabolites were identified. These 13 metabolites belong to the gelsemine, koumine, gelsedine, humantenine, yohimbane, and sarpagine classes of alkaloids. The metabolic pathways included oxidation, demethylation and dehydrogenation. After preliminary identification, the metabolites detected in the four species were different. All 13 metabolites were detected in pig and rat microsomes, but no oxidative metabolites of Gelsedine-type alkaloids were detected in goat and human microsomes. CONCLUSION: In this study, Gelsemium elegans metabolic patterns in different species are clarified and the in vitro metabolism of Gelsemium elegans is investigated. It is of great significance for its clinical development and rational application.

From sub-Saharan Africa to China: Evolutionary history and adaptation of Drosophila melanogaster revealed by population genomics.

Drosophila melanogaster is a widely used model organism for studying environmental adaptation. However, the genetic diversity of populations in Asia is poorly understood, leaving a notable gap in our knowledge of the global evolution and adaptation of this species. We sequenced genomes of 292 D. melanogaster strains from various ecological settings in China and analyzed them along with previously published genome sequences. We have identified six global genetic ancestry groups, despite the presence of widespread genetic admixture. The strains from China represent a unique ancestry group, although detectable differentiation exists among populations within China. We deciphered the global migration and demography of D. melanogaster, and identified widespread signals of adaptation, including genetic changes in response to insecticides. We validated the effects of insecticide resistance variants using population cage trials and deep sequencing. This work highlights the importance of population genomics in understanding the genetic underpinnings of adaptation, an effort that is particularly relevant given the deterioration of ecosystems.

The Schizosaccharomyces pombe DEAD-box protein Mss116 is required for mitoribosome assembly and mitochondrial translation.

DEAD-box helicases are important players in mitochondrial gene expression, which is necessary for mitochondrial respiration. In this study, we characterized Schizosaccharomyces pombe Mss116 (spMss116), a member of the family of DEAD-box RNA helicases. Deletion of spmss116 in a mitochondrial intron-containing background significantly reduced the levels of mitochondrial DNA (mtDNA)-encoded cox1 and cob1 mRNAs and impaired mitochondrial translation, leading to a severe respiratory defect and a loss of cell viability during stationary phase. Deletion of mitochondrial introns restored the levels of cox1 and cob1 mRNAs to wide-type (WT) levels but could not restore mitochondrial translation and respiration in Δspmss116 cells. Furthermore, deletion of spmss116 in both mitochondrial intron-containing and intronless backgrounds impaired mitoribosome assembly and destabilization of mitoribosomal proteins. Our findings suggest that defective mitochondrial translation caused by deletion of spmss116 is most likely due to impaired mitoribosome assembly.

Manipulating Crystal Growth and Secondary Phase PbI2 to Enable Efficient and Stable Perovskite Solar Cells with Natural Additives.

In perovskite solar cells (PSCs), the inherent defects of perovskite film and the random distribution of excess lead iodide (PbI2) prevent the improvement of efficiency and stability. Herein, natural cellulose is used as the raw material to design a series of cellulose derivatives for perovskite crystallization engineering. The cationic cellulose derivative C-Im-CN with cyano-imidazolium (Im-CN) cation and chloride anion prominently promotes the crystallization process, grain growth, and directional orientation of perovskite. Meanwhile, excess PbI2 is transferred to the surface of perovskite grains or formed plate-like crystallites in local domains. These effects result in suppressing defect formation, decreasing grain boundaries, enhancing carrier extraction, inhibiting non-radiative recombination, and dramatically prolonging carrier lifetimes. Thus, the PSCs exhibit a high power conversion efficiency of 24.71%. Moreover, C-Im-CN has multiple interaction sites and polymer skeleton, so the unencapsulated PSCs maintain above 91.3% of their initial efficiencies after 3000 h of continuous operation in a conventional air atmosphere and have good stability under high humidity conditions. The utilization of biopolymers with excellent structure-designability to manage the perovskite opens a state-of-the-art avenue for manufacturing and improving PSCs.

Biologically active isoquinoline alkaloids covering 2019-2022.

Isoquinoline alkaloids are an important class of natural products that are abundant in the plant kingdom and exhibit a wide range of structural diversity and biological activities. With the deepening of research in recent years, more and more isoquinoline alkaloids have been isolated and identified and proved to contain a variety of biological activities and pharmacological effects. In this review, we introduce the research progress of isoquinoline alkaloids from 2019 to 2022, mainly in the part of biological activities, including antitumor, antimicrobial, antidiabetic, antiviral, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, analgesic, and other activities. This study provides a clear direction for the rational development and utilization of isoquinoline alkaloids, suggesting that these alkaloids have great potential in the field of drug research.

Single-cell sequencing analysis of chronic subdural hematoma cell subpopulations and their potential therapeutic mechanisms.

BACKGROUND: Chronic subdural hematoma (CSDH) is a prevalent form of intracranial haemorrhage encountered in neurosurgical practice, and its incidence has notably risen in recent years. Currently, there is a lack of studies that have comprehensively classified the cells present in hematomas removed during surgery, and their correlation with CSDH recurrence remains elusive. This study aims to analyse the subcellular populations and occupancy levels within peripheral blood. METHODS: This study analyses the subcellular populations and occupancy levels within peripheral blood and postoperatively removed hematomas by single-cell sequencing and attempts to analyse the effect of different cell occupancies within peripheral blood and intraoperatively removed hematomas on CSDH. RESULTS: The single-cell sequencing results showed that the cells were classified into 25 clusters by differential gene and UMAP dimensionality reduction clustering analyses and further classified into 17 significant cell populations by cell markers: pDCs, CD8 T cells, CD4 T cells, MigDCs, cDC2s, cDC1s, plasma cells, neutrophils, naive B cells, NK cells, memory B cells, M2 macrophages, CD8 Teffs, CD8 MAIT cells, CD4 Tregs, CD19 B cells, and monocytes. Further research showed that the presence of more cDC2 and M2 macrophages recruited at the focal site in patients with CSDH and the upregulation of the level of T-cell occupancy may be a red flag for further brain damage. ROS, a marker of oxidative stress, was significantly upregulated in cDC2 cells and may mediate the functioning of transcription proteins of inflammatory factors, such as NFκB, which induced T cells' activation. Moreover, cDC2 may regulate M2 macrophage immune infiltration and anti-inflammatory activity by secreting IL1ß and binding to M2 macrophage IL1R protein. CONCLUSION: The detailed classification of cells in the peripheral blood and hematoma site of CSDH patients helps us to understand the mechanism of CSDH generation and the reduction in the probability of recurrence by regulating the ratio of cell subpopulations.

Sls1 and Mtf2 mediate the assembly of the Mrh5C complex required for activation of cox1 mRNA translation.

Mitochondrial translation depends on mRNA-specific activators. In Schizosaccharomyces pombe, DEAD-box protein Mrh5, pentatricopeptide repeat (PPR) protein Ppr4, Mtf2, and Sls1 form a stable complex (designated Mrh5C) required for translation of mitochondrial DNA (mtDNA)-encoded cox1 mRNA, the largest subunit of the cytochrome c oxidase complex. However, how Mrh5C is formed and what role Mrh5C plays in cox1 mRNA translation have not been reported. To address these questions, we investigated the role of individual Mrh5C subunits in the assembly and function of Mrh5C. Our results revealed that Mtf2 and Sls1 form a subcomplex that serves as a scaffold to bring Mrh5 and Ppr4 together. Mrh5C binds to the small subunit of the mitoribosome (mtSSU), but each subunit could not bind to the mtSSU independently. Importantly, Mrh5C is required for the association of cox1 mRNA with the mtSSU. Finally, we investigated the importance of the signature DEAD-box in Mrh5. We found that the DEAD-box of Mrh5 is required for the association of Mrh5C and cox1 mRNA with the mtSSU. Unexpectedly, this motif is also required for the interaction of Mrh5 with other Mrh5C subunits. Altogether, our results suggest that Mrh5 and Ppr4 cooperate in activating the translation of cox1 mRNA. Our results also suggest that Mrh5C activates the translation of cox1 mRNA by promoting the recruitment of cox1 mRNA to the mtSSU.

Redox Molecular Junction Metal-Covalent Organic Frameworks for Light-assisted CO2 Energy Storage.

Visible-light sensitive and bi-functionally favored CO2 reduction (CRR)/evolution (CER) photocathode catalysts that can get rid of the utilization of ultraviolet light and improve sluggish kinetics is demanded to conquer the current technique-barrier of traditional Li-CO2 battery. Here, a kind of redox molecular junction sp2c metal-covalent organic framework (i.e. Cu3-BTDE-COF) has been prepared through the connection between Cu3 and BTDE and can serve as efficient photocathode catalyst in light-assisted Li-CO2 battery. Cu3-BTDE-COF with redox-ability, visible-light-adsorption region, electron-hole separation ability and endows the photocathode with excellent round-trip efficiency (95.2 %) and an ultralow voltage hysteresis (0.18 V), outperforming the Schiff base COFs (i.e. Cu3-BTDA-COF and Cu3-DT-COF) and majority of the reported photocathode catalysts. Combined theoretical calculations with characterizations, Cu3-BTDE-COF with the integration of Cu3 centers, thiazole and cyano groups possess strong CO2 adsorption/activation and Li+ interaction/diffusion ability to boost the CRR/CER kinetics and related battery property.

Technological progress and coupling renewables enable substantial environmental and economic benefits from coal-to-olefins.

China's growing demand for bulk chemicals and concerns regarding energy security are scaling up coal-to-olefins (CTO) production. Three generations of independent dimethyl ether/methanol-to-olefins technologies have been successively launched with greatly improved production efficiencies. However, to date, widespread concerns regarding the intensive environmental impacts and potential economic risks have not been addressed in the context of this industrialization. Here we show that, through the technological progress from the first to the third generation, life cycle energy consumption, water consumption, and carbon emissions can be reduced to 119.5 GJ/t, 27.6 t/t, and 9.1 t CO2-eq/t, respectively, and human health damage, ecosystem quality damage, and resource scarcity impacts can be decreased by 40.5 %, 50.1 %, and 16.4 %, respectively. This is accompanied by an excellent performance in terms of production cost, net present value, and internal return rate at 792.5 USD/t, 173.4 USD/t, and 19.4 %, respectively. Substantial environmental and economic benefits can be gained by coupling renewables in the form of using green hydrogen from solar and wind power to synthesize methanol. Particularly, life cycle carbon emissions and resource scarcity impacts are reduced by 23.4 % and 22.4 %, respectively, exceeding the reduction in technological progress. However, coupling renewables increases the life cycle energy consumption to 154.5 GJ/t, counteracting the benefits of technological progress. Our results highlight the importance of technological progress and coupled renewables for enhancing the sustainability of the CTO industry.

Precision fermentation for improving the quality, flavor, safety, and sustainability of foods.

Precision fermentation involves the rewiring of metabolic pathways in generally recognized as safe microorganisms, fermentation scale-up, and downstream processing to produce food ingredients from abundant and inexpensive substrates. Using precise genome editing of food-fermenting microorganisms, precision fermentation can also produce fermented foods with more desirable properties. These genetic tools allow for the manipulation of flavors and nutritional content in fermented foods, the economic production of functional food ingredients, and the sustainable production of otherwise-costly macronutrients. By introducing the metabolic designs, genetic modifications, and resulting products of engineered microorganisms developed through academic and industrial research, this review aims to provide insights into the potentials and challenges of precision fermentation for the economic, safe, and sustainable production of foods.

Biosynthesis of Bt-Ag2O nanoparticles using Bacillus thuringiensis and their pesticidal and antimicrobial activities.

Nanosilver oxide exhibits strong antibacterial and photocatalytic properties and has shown great application potential in food packaging, biochemical fields, and other fields involving diseases and pest control. In this study, Ag2O nanoparticles were synthesized using Bacillus thuringiensis (Bt-Ag2O NPs). The physicochemical characteristics of the Bt-Ag2O NPs were analyzed by UV‒vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscope (SEM), inductively coupled plasma emission spectrometry (ICP), high-resolution transmission electron microscopy (HR-TEM), and zeta potential. The phis-chemical characterization revealed that the Bt-Ag2O NPs are in spherical shape with the small particle size (18.24 nm), high crystallinity, well dispersity, and stability. The biopesticidal and antifungal effects of Bt-Ag2O NPs were tested against Tribolium castaneum, Aspergillus flavus, and Penicillium chrysogenum. The survival, growth, and reproduction of tested pests and molds were significantly inhibited by Bt-Ag2O NPs in a dose-dependent manner. Bt-Ag2O NPs showed higher pesticidal activities against T. castaneum than Bt and commercial Ag2O NPs. The LC50 values of Bt, Ag2O NPs, and Bt-Ag2O NPs were 0.139%, 0.072%, and 0.06% on day 14, respectively. The Bt-Ag2O NPs also showed well antifungal activities against A. flavus and P. chrysogenum, while it resulted a small inhibition zone than commercial Ag2O NPs did. In addition, A. flavus showed much more sensitive to Bt-Ag2O NP treatments, compared to P. chrysogenum. Our results revealed that Bt-Ag2O NPs synthesized using B. thuringiensis could act as pesticides and antifungal agents in stored-product fields. KEY POINTS: • Bt-Ag2O NPs could be synthesized using Bacillus thuringiensis (Bt). • The NPs showed a high degree of crystallinity, spherical shape, and small particle size. • The NPs also showed excellent insecticidal and antifungal activity.

Treadmill exercise can regulate the redox balance in the livers of APP/PS1 mice and reduce LPS accumulation in their brains through the gut-liver-kupffer cell axis.

A growing body of clinical data has shown that patients with Alzheimer's disease (AD) have symptoms such as liver dysfunction and microbial-gut-brain axis dysfunction in addition to brain pathology, presenting a systemic multisystemic pathogenesis. Considering the systemic benefits of exercise, here, we first observed the effects of long-term treadmill exercise on liver injuries in APP/PS1 transgenic AD mice and explored the potential mechanisms of the gut-liver-brain axis's role in mediating exercise's ability to reduce bacterial lipopolysaccharide (LPS) pathology in the brain. The results showed that the livers of the AD mice were in states of oxidative stress, while the mice after long-term treadmill exercise showed alleviation of their oxidative stress, their intestinal barriers were protected, and the ability of their Kupffer cells to hydrolyze LPS was improved, in addition to the accumulation of LPS in their brains being reduced. Notably, the livers of the AD mice were in immunosuppressed states, with lower pro-oxidative and antioxidative levels than the livers of the wild-type mice, while exercise increased both their oxidative and antioxidative levels. These results suggest that long-term exercise modulates hepatic redox homeostasis in AD mice, attenuates oxidative damage, and reduces the accumulation of LPS in the brain through the combined action of the intestine-liver-Kupffer cells.

The soil emergence-related transcription factor PIF3 controls root penetration by interacting with the receptor kinase FER.

The cotyledons of etiolated seedlings from terrestrial flowering plants must emerge from the soil surface, while roots must penetrate the soil to ensure plant survival. We show here that the soil emergence-related transcription factor PHYTOCHROME-INTERACTING FACTOR 3 (PIF3) controls root penetration via transducing external signals perceived by the receptor kinase FERONIA (FER) in Arabidopsis thaliana. The loss of FER function in Arabidopsis and soybean (Glycine max) mutants resulted in a severe defect in root penetration into agar medium or hard soil. Single-cell RNA sequencing (scRNA-seq) profiling of Arabidopsis roots identified a distinct cell clustering pattern, especially for root cap cells, and identified PIF3 as a FER-regulated transcription factor. Biochemical, imaging, and genetic experiments confirmed that PIF3 is required for root penetration into soil. Moreover, FER interacted with and stabilized PIF3 to modulate the expression of mechanosensitive ion channel PIEZO and the sloughing of outer root cap cells.

Insights into the roles of non-coding RNAs and angiogenesis in glioblastoma: An overview of current research and future perspectives.

Glioblastoma (GBM) is a highly aggressive type of primary brain cancer with a poor prognosis, and despite intensive research, survival rates have not significantly improved. Non-coding RNAs (ncRNAs) are emerging as critical regulators of GBM pathogenesis, including angiogenesis, which is essential for tumor growth and invasion. MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) have been identified as regulators of angiogenesis in GBM. miRNAs such as miR-21, miR-10b, and miR-26a promote angiogenesis by targeting anti-angiogenic factors, while lncRNAs such as H19 and MALAT1 inhibit angiogenesis by regulating pro-angiogenic factors. CircRNAs, such as circSMARCA5 and circBACH2, also regulate angiogenesis through various mechanisms. Similarly, signaling pathways such as the vascular endothelial growth factor (VEGF) pathway play critical roles in angiogenesis and have been targeted for GBM therapy. However, resistance to anti-angiogenic therapies is a significant obstacle in clinical practice. Developing novel therapeutic strategies targeting ncRNAs and angiogenesis is a promising approach for GBM. Potential targets include miRNAs, lncRNAs, circRNAs, and downstream signaling pathways that regulate angiogenesis. This review highlights the critical roles of ncRNAs and angiogenesis in GBM pathogenesis and the potential for new therapeutic strategies targeting these pathways to improve the prognosis and quality of life for GBM patients.

Tailoring the Hydrophobic Interface of Core-Shell HKUST-1@Cu2O Nanocomposites for Efficiently Selective CO2 Electroreduction.

The electrochemical reduction of carbon dioxide (CO2) to ethylene creates a carbon-neutral approach to converting carbon dioxide into intermittent renewable electricity. Exploring efficient electrocatalysts with potentially high ethylene selectivity is extremely desirable, but still challenging. In this report, a laboratory-designed catalyst HKUST-1@Cu2O/PTFE-1 is prepared, in which the high specific surface area of the composites with improved CO2 adsorption and the abundance of active sites contribute to the increased electrocatalytic activity. Furthermore, the hydrophobic interface constructed by the hydrophobic material polytetrafluoroethylene (PTFE) effectively inhibits the occurrence of hydrogen evolution reactions, providing a significant improvement in the efficiency of CO2 electroreduction. The distinctive structures result in the remarkable hydrocarbon fuels generation with high Faraday efficiency (FE) of 67.41%, particularly for ethylene with FE of 46.08% (-1.0 V vs RHE). The superior performance of the catalyst is verified by DFT calculation with lower Gibbs free energy of the intermediate interactions with improved proton migration and selectivity to emerge the polycarbon（C2+） product. In this work, a promising and effective strategy is presented to configure MOF-based materials with tailored hydrophobic interface, high adsorption selectivity and more exposed active sites for enhancing the efficiency of the electroreduction of CO2 to C2+ products with high added value.

SCH772984 ameliorates lipopolysaccharide-induced hypoglycemia in mice through reversing MEK/ERK/Foxo1-mediated gluconeogenesis suppression.

Lipopolysaccharide (LPS) results in a lethal hypoglycemic response. However, the main molecular mechanism involved in LPS-induced glucose metabolism disorder is poorly understood. This study intends to investigate the signaling pathways involved in LPS-induced hypoglycemia and potential efficacy of extracellular signal-regulated kinase (ERK) inhibitor SCH772984. The effects of LPS and SCH772984 on gluconeogenesis, glucose absorption, and glycogenolysis were evaluated by pyruvate tolerance test, oral glucose tolerance test, and glucagon test, respectively. After a single intraperitoneal injection of 0.5 mg/kg LPS, the mice's blood glucose levels and gluconeogenesis ability were significantly lower than that of control group. Besides, mRNA and protein expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK) decreased significantly after LPS treatment. LPS induced the phosphorylation of ERK1/2, MEK1/2 (mitogen-activated protein kinase), and Foxo1 while inhibited Foxo1 expression in the nucleus, indicating an important role of the MEK/ERK/Foxo1 signaling in the inhibition of gluconeogenesis by LPS. Furthermore, SCH772984 elevated blood glucose, increased the G6Pase and PEPCK expression, and inhibited pERK1/2 and pFoxo1 expression in LPS-induced mice. In summary, LPS inhibited gluconeogenesis and induced hypoglycemia through the MEK/ERK/Foxo1 signal pathway, and ERK inhibitor could effectively reverse decreased blood glucose in mice with LPS treatment. These findings provide a novel therapeutic target for LPS-induced hypoglycemia.

Convergent and divergent evolution of microRNA-mediated regulation in metazoans.

The evolution of microRNAs (miRNAs) has been studied extensively to understand their roles in gene regulation and evolutionary processes. This review focuses on how miRNA-mediated regulation has evolved in bilaterian animals, highlighting both convergent and divergent evolution. Since animals and plants display significant differences in miRNA biogenesis and target recognition, the 'independent origin' hypothesis proposes that miRNA pathways in these groups independently evolved from the RNA interference (RNAi) pathway, leading to modern miRNA repertoires through convergent evolution. However, recent evidence raises the alternative possibility that the miRNA pathway might have already existed in the last common ancestor of eukaryotes, and that the differences in miRNA pathway and miRNA repertoires among animal and plant lineages arise from lineage-specific innovations and losses of miRNA pathways, miRNA acquisition, and loss of miRNAs after eukaryotic divergence. The repertoire of miRNAs has considerably expanded during bilaterian evolution, primarily through de novo creation and duplication processes, generating new miRNAs. Although ancient functionally established miRNAs are rarely lost, many newly emerged miRNAs are transient and lineage specific, following a birth-death evolutionary pattern aligning with the 'out-of-the-testis' and 'transcriptional control' hypotheses. Our focus then shifts to the convergent molecular evolution of miRNAs. We summarize how miRNA clustering and seed mimicry contribute to this phenomenon, and we review how miRNAs from different sources converge to degrade maternal messenger RNAs (mRNAs) during animal development. Additionally, we describe how miRNAs evolve across species due to changes in sequence, seed shifting, arm switching, and spatiotemporal expression patterns, which can result in variations in target sites among orthologous miRNAs across distant strains or species. We also provide a summary of the current understanding regarding how the target sites of orthologous miRNAs can vary across strains or distantly related species. Although many paralogous miRNAs retain their seed or mature sequences after duplication, alterations can occur in the seed or mature sequences or expression patterns of paralogous miRNAs, leading to functional diversification. We discuss our current understanding of the functional divergence between duplicated miRNAs, and illustrate how the functional diversification of duplicated miRNAs impacts target site evolution. By investigating these topics, we aim to enhance our current understanding of the functions and evolutionary dynamics of miRNAs. Additionally, we shed light on the existing challenges in miRNA evolutionary studies, particularly the complexity of deciphering the role of miRNA-mediated regulatory network evolution in shaping gene expression divergence and phenotypic differences among species.

The role of tumor-associated macrophages in lung cancer: From mechanism to small molecule therapy.

Tumor-associated macrophages (TAMs) are the main component of tumor-infiltrating immune cells in the lung tumor microenvironment. TAMs recruited to the lung cancer can create a suitable microenvironment for the growth and metastasis of lung cancer by secreting tumor promoting factors and interfering with the function of T cells. Currently, numerous studies have reported that small molecular drugs affect lung cancer progression by selectively targeting TAMs. The main ways include blocking the recruitment of monocytes or eliminating existing TAMs in tumor tissue, reprogramming TAMs into pro-inflammatory M1 macrophages or inhibiting M2 polarization of macrophages, interrupting the interaction between tumor cells and macrophages, and modulating immune function. Signaling pathways or cytokines such as CCL8, CCL2/CCR2, CSF-1/CSF-1R, STAT3, STAT6, MMPs, Caspase-8, AMPK α1, TLR3, CD47/SIRPα, have been reported to be involved in this process. Based on summarizing the role and mechanisms of TAMs in lung cancer progression, this paper particularly focuses on systematically reviewing the effects and mechanisms of small molecule drugs on lung cancer TAMs, and classified the small molecular drugs according to the way they affect TAMs. The study aims to provide new perspectives and potential therapeutic drugs for targeted macrophages treatment in lung cancer, which is of great significance and will provide more options for immunotherapy of lung cancer.

Non-aqueous Liquid Electrolyte Additives for Sodium-Ion Batteries.

Sodium-ion batteries (SIBs) have been recognized as one of the most promising new energy storage devices for their rich sodium resources, low cost and high safety. The electrolyte, as a bridge connecting the cathode and anode electrodes, plays a vital role in determining the performance of SIBs, such as coulombic efficiency, energy density and cycle life. Therefore, the overall performance of SIBs could be significantly improved by adjusting the electrolyte composition or adding a small number of functional additives. In this review, the fundamentals of SIB electrolytes including electrode-electrolyte interface and solvation structure are introduced. Then, the mechanisms of electrolyte additive action on SIBs are discussed, with a focus on film-forming additives, flame-retardant additives and overcharge protection additives. Finally, the future research of electrolytes is prospected from the perspective of scientific concepts and practical applications.