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Metabolic reprogramming is one of the main characteristics of malignant tumors, which is due to the flexible changes of cell metabolism that can meet the needs of cell growth and maintain the homeostasis of tissue environments. Cancer cells can obtain metabolic adaptation through a variety of endogenous and exogenous signaling pathways, which can not only promote the growth of malignant cancer cells, but also start the transformation process of cells to adapt to tumor microenvironment. Studies show that m6A RNA methylation is widely involved in the metabolic recombination of tumor cells. In eukaryotes, m6A methylation is the most abundant modification in mRNA, which is involved in almost all the RNA cycle stages, including regulation the transcription, maturation, translation, degradation and stability of mRNA. M6A RNA methylation can be involved in the regulation of physiological and pathological processes, including cancer. In this review, we discuss the role of m6A RNA methylation modification plays in tumor metabolism-related molecules and pathways, aiming to show the importance of targeting m6A in regulating tumor metabolism.

Osteoporosis (OP) is distinguished by a reduction in bone mass and degradation of bone micro-structure, frequently resulting in fractures. As the geriatric demographic expands, the incidence of affected individuals progressively rises, thereby exerting a significant impact on the quality of life experienced by individuals. The flavonoid compound hesperidin has been subject to investigation regarding its effects on skeletal health, albeit the precise mechanisms through which it operates remain ambiguous. This study utilized network pharmacology to predict the core targets and signaling pathways implicated in the anti-OP properties of hesperidin. Molecular docking and molecular dynamics simulations were employed to confirm the stability of the interaction between hesperidin and the core targets. The effects of hesperidin on osteoblastic cells MC3T3-E1 were assessed using MTT, ELISA, alkaline phosphatase assay, and RT-qPCR techniques. Furthermore, in vivo experiments were conducted to determine the potential protective effects of hesperidin on zebrafish bone formation and oxidative stress response. The results demonstrate that network pharmacology has identified 10 key target points, significantly enriched in the estrogen signaling pathway. Hesperidin exhibits notable promotion of MC3T3-E1 cell proliferation and significantly enhances ALP activity. ELISA measurements indicate an elevation in NO levels and a reduction in IL-6 and TNF-α. Moreover, RT-qPCR analysis consistently reveals that hesperidin significantly modulates the mRNA levels of ESR1, SRC, AKT1, and NOS3 in MC3T3-E1 cells. Hesperidin promotes osteogenesis and reduces oxidative stress in zebrafish. Additionally, we validate the stable and tight binding of hesperidin with ESR1, SRC, AKT1, and NOS3 through molecular dynamics simulations. In conclusion, our comprehensive analysis provides evidence that hesperidin may exert its effects on alleviating OP through the activation of the estrogen signaling pathway via ESR1. This activation leads to the upregulation of SRC, AKT, and eNOS, resulting in an increase in NO levels. Furthermore, hesperidin promotes osteoblast-mediated bone formation and inhibits pro-inflammatory cytokines, thereby alleviating oxidative stress associated with OP.

Light intensity ( I ) is the most dynamic and significant environmental variable affecting photosynthesis ( A n), stomatal conductance ( g s), transpiration ( T r), and water-use efficiency (WUE). Currently, studies characterizing leaf-scale WUE– I responses are rare and key questions have not been answered. In particular, (1) What shape does the response function take? (2) Are there maximum intrinsic (WUEi; WUEi–max) and instantaneous WUE (WUEinst; WUEinst–max) at the corresponding saturation irradiances ( I i–sat and I inst–sat)? This study developed WUEi– I and WUEinst– I models sharing the same non-asymptotic function with previously published A n– I and g s– I models. Observation-modeling intercomparison was conducted for field-grown plants of soybean (C3) and grain amaranth (C4) to assess the robustness of our models versus the non-rectangular hyperbola models (NH models). Both types of models can reproduce WUE– I curves well over light-limited range. However, at light-saturated range, NH models overestimated WUEi–max and WUEinst–max and cannot return I i–sat and I inst–sat due to its asymptotic function. Moreover, NH models cannot describe the down-regulation of WUE induced by high light, on which our models described well. The results showed that WUEi and WUEinst increased rapidly within low range of I , driven by uncoupled photosynthesis and stomatal responsiveness. Initial response rapidity of WUEi was higher than WUEinst because the greatest increase of A n and T r occurred at low g s. C4 species showed higher WUEi–max and WUEinst–max than C3 species—at similar I i–sat and I inst–sat. Our intercomparison highlighted larger discrepancy between WUEi– I and WUEinst– I responses in C3 than C4 species, quantitatively characterizing an important advantage of C4 photosynthetic pathway—higher A n gain but lower T r cost per unit of g s change. Our models can accurately return the wealth of key quantities defining species-specific WUE– I responses—besides A n– I and g s– I responses. The key advantage is its robustness in characterizing these entangled responses over a wide I range from light-limited to light-inhibitory light intensities, through adopting the same analytical framework and the explicit and consistent definitions on these responses. Our models are of significance for physiologists and modelers—and also for breeders screening for genotypes concurrently achieving maximized photosynthesis and optimized WUE.

Wireless cellular traffic prediction is a critical issue for researchers and practitioners in the 5G/B5G field. However, it is very challenging since the wireless cellular traffic usually shows high nonlinearities and complex patterns. Most existing wireless cellular traffic prediction methods lack the abilities of modeling the dynamic spatial–temporal correlations of wireless cellular traffic data, thus cannot yield satisfactory prediction results. In order to improve the accuracy of 5G/B5G cellular network traffic prediction, an attention-based multi-component spatiotemporal cross-domain neural network model (att-MCSTCNet) is proposed, which uses Conv-LSTM or Conv-GRU for neighbor data, daily cycle data, and weekly cycle data modeling, and then assigns different weights to the three kinds of feature data through the attention layer, improves their feature extraction ability, and suppresses the feature information that interferes with the prediction time. Finally, the model is combined with timestamp feature embedding, multiple cross-domain data fusion, and jointly with other models to assist the model in traffic prediction. Experimental results show that compared with the existing models, the prediction performance of the proposed model is better. Among them, the RMSE performance of the att-MCSTCNet (Conv-LSTM) model on Sms, Call, and Internet datasets is improved by 13.70 ~ 54.96%, 10.50 ~ 28.15%, and 35.85 ~ 100.23%, respectively, compared with other existing models. The RMSE performance of the att-MCSTCNet (Conv-GRU) model on Sms, Call, and Internet datasets is about 14.56 ~ 55.82%, 12.24 ~ 29.89%, and 38.79 ~ 103.17% higher than other existing models, respectively.

Hyriopsis cumingii is an important species for freshwater pearl cultivation in China. In terms of pearl production, males have larger pearls and better glossiness than females, but there are few reports focusing on the sex of H. cumingii . In this study, six mRNA and six microRNA (miRNA) libraries were prepared from ovaries and testes. Additionally, 28,502 differentially expressed genes (DEGs) and 32 differentially expressed miRNAs (DEMs) were identified. Compared with testis, 14,360 mRNAs and 20 miRNAs were up-regulated in ovary, 14,142 mRNAs and 12 miRNAs were down-regulated. In DEGs, the known genes related to sex determinism and/or differentiation were also identified, such as DMRT1 , SOX9 , SF1 for males, FOXL2 for females, and other potentially significant candidate genes. Three sex-related pathways have also been identified, which are Wnt, Notch, and TGF-beta. In 32 DEMs, the three miRNAs (miR-9-5p, miR-92, miR-184) were paid more attention, they predicted 28 target genes, which may also be candidates for sex-related miRNAs and genes. Differential miRNAs target genes analysis reveals the pathway associated with oocyte meiosis and spermatogenesis. Overall, the findings of the study provide significant insights to enhance our understanding of sex differentiation and/or sex determination mechanisms for H. cumingii .

Background Macrophages play an essential role in regulating ovarian cancer immune microenvironment. Studies have shown that m6A methylation could influence immune microenvironment in cancer. In this study, we investigated the roles of m6A demethylase ALKBH5 and m6A recognition protein IGF2BP2 played in regulating macrophages polarization in ovarian cancer. Methods In this study, we first explored the differentially expressed m6A methylation enzymes in M0 and M2 macrophages according to two independent GEO datasets. TIMER2.0 and GSCA database were used to explore the immune analysis of ALKBH5 and IGF2BP2 in ovarian cancer. K-M plotter and TIMER2.0 databases were used to evaluate the prognostic role of ALKBH5 and IGF2BP2 in ovarian cancer. For CNV mutation analysis of ALKBH5 and IGF2BP2, cBioPortal and GSCA databases were used. For single-cell analysis, sc-TIME and HPA softwares were used to analyze the roles of ALKBH5 and IGF2BP2 played in immune cells in ovarian cancer. To identify the role of ALKBH5 played in macrophage polarization, RT-PCR was used to verify the macrophage polarization related markers in vitro study. The function of ALKBH5 played in ovarian cancer was further analyzed through GO and KEGG analysis. Findings In this study, we found that ALKBH5 and IGF2BP2 were up-regulated in M2 macrophages, which showed closely correlation with immune cells expressions in ovarian cancer, especially with macrophages. Ovarian cancer patients with higher expression of ALKBH5 and IGF2BP2 showed worse prognosis, possibly because of their close correlation with immune response. ALKBH5 also correlated with macrophage phenotypes in single-cell levels analysis. However, the expression level of IGF2BP2 in ovarian cancer immune microenvironment was very low. The results of RT-PCR indicated the potential role of ALKBH5 in M2 polarization of macrophages. Interpretation ALKBH5 participated in regulating macrophage M2 polarization in ovarian cancer immune microenvironment.

The pre-metastatic niche (PMN) represents the microenvironment established in target organs before primary tumor metastasis, playing a crucial role in organ-specific metastasis. Understanding and preventing PMN formation holds promise for enhancing immunotherapy efficacy and reducing cancer-related mortality. Despite the significance of this field, a comprehensive bibliometric analysis is lacking. This study aims to identify global research trends and hotspots in PMN through a systematic bibliometric evaluation, providing a foundation for future advancements in this field. Publications related to PMN research from 2005 to 2024 were retrieved from the Web of Science Core Collection database. Bibliometric analyses and visualizations were conducted using VOSviewer, CiteSpace, Microsoft Excel, ArcGIS, Scimago Graphica, and Microsoft Charticulator. The study included 1,303 publications authored by 7,955 researchers from 1,627 institutions across 62 countries, with articles published in 400 journals. China and the United States emerged as central contributors to global PMN research. China has led in publication volume and institutional representation, while the United States has produced the most high-quality papers and impactful authors. published the most PMN-related papers, while had the most citations and co-citations. Professor David Lyden of Cornell University, USA, was identified as the most influential scholar in the field. Analysis of references and keywords suggests future research will focus on metastatic organotropism, extracellular vesicles, innate immunocytes (e.g., macrophages and neutrophils), and immunotherapy. This bibliometric study represents the first comprehensive analysis of global scientific output in PMN research over the past two decades. By summarizing the current status and identifying trends in the field, this study provides valuable insights and a reference point for researchers aiming to prevent and treat tumor metastasis effectively.

Circular RNAs (circRNAs) are a new type of intracellular regulator that have been widely identified in animals and plants by high-throughput sequencing. However, there are still few functional studies on circRNAs in plants. To better understand maize circRNAs and their potential functions, we identified 1199 circRNAs in maize from RiboMinus RNA-Seq transcriptome data, and found distinct features of splicing site selection bias, longer flanking introns, and miniature inverted-repeat transposable element (MITE) insertions in flanking introns in maize circRNAs compared to other plant circRNAs. In total, 31 and 36 orthologous circRNAs were identified in rice and maize, respectively, but the orthologous parental genes could not produce orthologous circRNAs, mostly because of long-sequence insertions/deletions at flanking introns and approximately 24.3% of them contained MITE sequences. The majority of maize circRNAs showed high diversity of expression under different treatments and/or in different genetic backgrounds, implying that circRNAs could be involved in various regulatory networks. Twenty-six ecircRNAs were predicted to contain one or more target mimics, and 229 circRNAs had high coding potential, indicating that circRNAs could perform peptide-encoding functions in plants. These results will broaden understanding of the roles of circRNAs in plants and support further functional work on maize.

Aim： Chinese medicine CGA formula consists of polysaccharide from Cordyceps sinensis mycelia （CS-PS）, gypenosides and amygdalin, which is derived from Fuzheng Huayu （FZHY） capsule for treating liver fibrosis. In this study we attempted to confirm the therapeutic effects of CGA formula in dimethylnitrosamine （DMN）-induced liver fibrosis in rats, and to identify the mechanisms of anti-fibrotic actions. Methods： Rats were injected with DMN （10 mg.kg-l.d-1, ip） for 3 consecutive days per week over a 4-week period. The rats then were orally administered with CGA formula （CS-PS 60 mg.kg-1.-1, gypenosides 50 mg.kg-1.d-1 and amygdalin 80 mg.kg-1.d-1） daily in the next 2 weeks. CS-PS, gypenosides or amygdalin alone were administered as individual component controls, whereas colchicine and FZHY were used as positive controls. Serum biomarkers were measured. Hepatic injury, collagen deposition and stellate cell activation were examined. The MMP activities, expression of TIMP protein and proteins involved in the TGF-β1/Smad signaling pathways in liver tissues were assayed. Results： In DMN-treated rats, administration of CGA formula significantly decreased serum ALT, AST and total bilirubin and hepatic hydroxyproline levels, increased serum albumin level, and attenuated liver fibrosis as shown by histological examination. Furthermore, these effects were comparable to those caused by administration of FZHY, and superior to those caused by administration of colchicine or the individual components of CGA formula. Moreover, administration of CGA formula significantly decreased the protein levels of a-SMA, TGF-β1, TGF-β1 receptor （TI3R-I）, p-T-R-I, p-TI3R-II, p-Smad2, p-Smad3, TIMP1 and TIMP2, as well as MMP2 and MMP9 activities in liver tissues of DMN-treated rats. Conclusion： Chinese medicine CGA formula ameliorates DMN-induced liver fibrosis in rats, and this effect was likely associated with the down-regulation of MMP2/9 activities, TIMP1/2 protein expression and the TGF-β1/Smad signaling pathways in the liver.

Difunctionalization of alkynes represents a powerful and straightforward approach to the synthesis of complex molecules. However, the radical difunctionalization of alkynes mediated by bifunctional reagents remains challenging and underexplored, despite significant progress having been made in alkene difunctionalization. Here, we report a novel arylsulfonylacetate skeleton in which aryl rings are attached to acetates through SO 2 , serving as a powerful bifunctional reagent for the alkylarylation of alkynes via vinyl-radical intermediate under photoredox conditions. This modular bifunctional reagent enables the simultaneous incorporation of a wide range of functional groups, including (hetero)aryl ring and alkyl carboxylate into alkynes, resulting in synthetically valuable all-carbon tetrasubstituted alkene derivatives. This transformation is distinguished by its redox-neutral nature, readily accessible starting materials, compatibility with diverse functional groups and its capacity to facilitate convergent synthesis. The utility of this approach was further demonstrated by the late-stage functionalization of complex molecules and the preparation of fluorescent molecules and anti-cancer drugs.