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Circular RNA (circRNAs) functions vital in the pathogenesis and progression of hepatocellular carcinoma (HCC). However, the expressions and functions of certain circRNAs on metastasis and proliferation of that cancer is still unclear. Bioinformation analysis and qRT-PCR indicated that CircC16orf62 was prominent upregulated in HCC of which the expression level was positively associated to cancer’s malignant progression. Gain or loss-of-function studies indicated that the reduction of CircC16orf62 expression promotes the proliferation, invasion, and glycolysis of HCC in vitro and in vivo. The bioinformatic analysis found that miR-138-5p and PTK2 were the downstream target of CircC16or62. Then, the FISH(Fluorescence immunoin situ hybridization) and cell nucleoplasmic separation determined that CircC16orf62 located in the cell cytoplasm. Plasmid vectors or siRNAs were used to change the expression of CircC16orf62, miR-138-5p, and PTK2 in PC cell lines. CircC16orf62 functioned as a molecular sponge for miR-138-5p, and a competitive endogenous RNA for PTK2, promoting AKT/mTOR pathway activation. Our observations lead us to conclude that CircC16orf62 functions as an oncogene in HCC progression, behaving as a competitive endogenous RNA for miR-138-5p binding, thus activating the AKT/mTOR pathway. In conclusion, CircC16orf62 is an oncogene through the miR-138-5p/PTK2/Akt axis in HCC cells, indicating CircC16orf62 can be a therapeutic target with potentiality for liver cancer and a predictive marker for people with HCC.

The application of nanomedicine in inflammatory bowel disease (IBD) has gained significant attention in the recent years. As the field rapidly evolves, analyzing research trends and identifying research hotpots are essential for guiding future advancements, and a comprehensive bibliometric can provide valuable insights. The current research focused on publications from 2001 to 2024, and was sourced from the Web of Science Core Collection (WoSCC). CiteSpace and VOSviewer were employed to visualize authors, institutions, countries, co-cited references, and keywords, thereby mapping the intellectual structure and identifying emerging trends in the field. The analysis covered 1,518 literature across 447 journals, authored by 9,334 researchers from 5,459 institutions and 287 countries/regions. The global publication numbers exhibited an upward trend, particularly in the last decade, with China leading as the top publishing country and the Chinese Academy of Sciences emerging as the foremost institution. Dr. Xiao Bo is the prominent figure in advanced drug delivery systems. This interdisciplinary field, which spans materials science, pharmacy, and medicine, has seen influential publications mainly concentrated on targeted nanoparticles treatment for IBD. Keyword analysis revealed that current research hotspots include drug delivery, immune cell regulation, antioxidant damage, intestinal microbiota homeostasis, and nanovesicles. This study offers a comprehensive overview of global research landscape, emphasizing the rapid growth and increasing complexity of this field. It identifies key research hotspots and trends, including efforts to enhance the precision, efficacy, and safety of nanomedicine applications. Emerging directions are highlighted as crucial for further progress in this evolving area.

This study aimed to analyze active compounds and signaling pathways of CH applying network pharmacology methods, and to additionally verify the molecular mechanism of CH in treating AP. Network pharmacology and molecular docking were firstly used to identify the active components of CH and its potential targets in the treatment of AP. The pancreaticobiliary duct was retrogradely injected with sodium taurocholate (3.5%) to create an acute pancreatitis (AP) model in rats. Histological examination, enzyme-linked immunosorbent assay, Western blot and TUNEL staining were used to determine the pathway and mechanism of action of CH in AP. Network pharmacological analysis identified 168 active compounds and 276 target proteins. In addition, there were 2060 targets associated with AP, and CH had 177 targets in common with AP. These shared targets, including STAT3, IL6, MYC, CDKN1A, AKT1, MAPK1, MAPK3, MAPK14, HSP90AA1, HIF1A, ESR1, TP53, FOS, and RELA, were recognized as core targets. Furthermore, we filtered out 5252 entries from the Gene Ontology(GO) and 186 signaling pathways from the Kyoto Encyclopedia of Genes and Genomes(KEGG). Enrichment and network analyses of protein-protein interactions predicted that CH significantly affected the PI3K/AKT signaling pathway, which played a critical role in programmed cell death. The core components and key targets showed strong binding activity based on molecular docking results. Subsequently, experimental validation demonstrated that CH inhibited the phosphorylation of PI3K and AKT in pancreatic tissues, promoted the apoptosis of pancreatic acinar cells, and further alleviated inflammation and histopathological damage to the pancreas in AP rats. Apoptosis of pancreatic acinar cells can be enhanced and the inflammatory response can be reduced through the modulation of the PI3K/AKT signaling pathway, resulting in the amelioration of pancreatic disease.

Endometrial regenerative cell-derived exosomes (ERC-Exos) exhibit tissue repair and anti-inflammatory properties for ulcerative colitis (UC) treatment, but oral administration is limited by gastrointestinal degradation. This study first developed chitosan-sodium alginate microcapsules (CSE) for ERC-Exos delivery and explored the role of milk fat globule-EGF factor 8 (MFGE8). MFGE8-knockdown ERC-Exos (MFGE8 -ERC-Exos) were constructed via lentiviral transfection. Colitis-targeted exosomes (CSE) were prepared, and their in vivo stability and targeting ability were verified. A dextran sulfate sodium (DSS)-induced murine colitis model was used to evaluate the effects of CSE. Immunofluorescence staining was utilized to assess colon DC infiltration; Flow cytometry was employed to detect CD4 T cell proliferation and dendritic cell (DC) maturation. EdU/TUNEL staining and Western blotting were performed to determine intestinal epithelial cell proliferation and apoptosis, as well as the activation level of the PI3K/AKT/mTOR pathway. CSE achieved 89.2%±1.5% encapsulation efficiency and 78% colon-targeted release, resisting gastric degradation. Oral CSE significantly alleviated DSS-induced weight loss ( <0.001), colon shortening ( <0.0001), and histopathological damage, while restoring intestinal barrier function (reduced permeability, <0.0001; upregulated tight junction proteins ZO-1/Occludin/Claudin-1). It also inhibited DC maturation (MLN: <0.0001; LP: <0.0001) and CD4⁺T cell proliferation (MLN: <0.001; LP: <0.01), and normalized cytokine profiles (reduced IL-6/IL-1β/TNF-α, <0.001; increased IL-10, <0.0001). MFGE8 knockdown significantly attenuated these effects. Mechanistically, MFGE8 mediated ERC-Exos uptake by intestinal epithelial cells via αvβ5 integrin, activating PI3K/AKT/mTOR to inhibit apoptosis (P<0.0001) and promote proliferation (P<0.0001). This study is the first to confirm that the CSE carrier achieves colonic targeted release, overcoming the limitations of oral exosome delivery. MFGE8 mediates the intestinal epithelial repair effect of ERC-Exos via the PI3K/AKT/mTOR pathway.

Through detailed morphological comparison and robust molecular evidence, we confirm Neillia daloushanensis M.T.An & Xu Wu as a new species of Rosaceae from Guizhou province, southwest China. Morphologically, N. daloushanensis closely resembles N. gracilis but differs in several key traits: it is a creeping liana rather than a low subshrub; its stems are 0.6–1.5 cm long compared to the slender stems less than 0.5 cm tall in N. gracilis ; its leaves are larger, measuring 5–9 × 3–6 cm vs. 2.5–3.5 × 2–3 cm; stipules are sessile, clasping, and larger (0.8–1.3 × 0.6–1.1 cm) rather than peitiolate and smaller (0.4–0.6 × 0.3–0.5 cm) without clasping; calyx tubes are densely pilose on both surfaces and bear stipitate glands abaxially, in contrast to the slightly pubescent, glandless calyx tubes of N. gracilis ; and the seed number ranges from 2 to 4 instead of consistently 2. These morphological distinctions are further corroborated by molecular phylogenetic analysis based on 703 single-copy nuclear genes, supporting the recognition of N. daloushanensis as a distinct species within the genus.

Background Renal ischemia reperfusion (I/R) injury is a major contributor to graft dysfunction and inflammation leading to graft loss. The deregulation of purinergic signaling has been implicated in the pathogenesis of renal I/R injury. CD73 and the generation of adenosine during purine metabolism to protect against renal I/R injury. A mesenchymal-like endometrial regenerative cell (ERC) has demonstrated a significant therapeutic effect on renal I/R injury. CD73 is a phenotypic marker of human endometrial regenerative cell exosomes (ERC-Exo). However, its immunosuppressive function in regulating purinergic metabolism has been largely neglected. Here, we investigate the protective effects and mechanism of ERC-Exo against renal I/R injury. Methods Lentivirus-mediated CRISPR-Cas9 technology was employed to obtain CD73-specific knockout ERC-Exo (CD73 −/− ERC-Exo). C57BL/6 mice who underwent unilateral ureteral obstruction were divided into the Untreated, ERC-Exo-treated, and CD73 −/− ERC-Exo-treated groups. Renal function and pathological injury were assessed 3 days after renal reperfusion. The infiltration of CD4 + T cells and macrophages was analyzed by flow cytometry and immunofluorescence staining in kidneys. CD73-mediated immunosuppressive activity of ERC-Exo was investigated by bone marrow-derived macrophages (BMDM) co-culture assay in vitro . Flow cytometry determined macrophage polarization. ELISA and Treg proliferation assays detected the function of macrophages. Furthermore, the role of the MAPK pathway in CD73-positive Exo-induced macrophage polarization was also elucidated. Results Compared with Untreated and CD73 −/− ERC-Exo-treated groups, CD73-positive Exo effectively improved the serum creatinine (sCr), blood urea nitrogen (BUN), and necrosis and detachment of tubular epithelial cells, necrosis and proteinaceous casts induced by ischemia. CD73 improved the capacity of ERC-Exo on CD4 + T cell differentiation in the renal immune microenvironment. Surprisingly, ERC-Exosomal CD73 significantly decreased the populations of M1 cells but increased the proportions of M2 in kidneys. Furthermore, CD73-positive Exo markedly reduced the levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) and increased anti-inflammatory factors (IL-10) level in kidneys. ERC-Exosomal CD73 improved macrophage immunoregulatory function associated with the MAPK pathway (including ERK1/2 and p38 pathways), which exerted a potent therapeutic effect against renal I/R. Conclusions These data collected insight into how ERC-Exo facilitated the hydrolysis of proinflammatory ATP to immunosuppressive ADO via CD73. CD73 is a critical modulator of the MAPK signaling pathway, inducing a polarization shift of macrophages towards an anti-inflammatory phenotype. This study highlights the significance of ERC-Exosomal CD73 in contributing to the therapeutic effects against renal I/R.

Cancer cells are addicted to glutamine. However, cancer cells often suffer from glutamine starvation, which largely results from the fast growth of cancer cells and the insufficient vascularization in the interior of cancer tissues. Herein, based on clinical samples, patient‐derived cells (PDCs), and cell lines, it is found that liver cancer cells display stem‐like characteristics upon glutamine shortage due to maintaining the stemness of tumor initiating cells (TICs) and even promoting transformation of non‐TICs into stem‐like cells by glutamine starvation. Increased expression of glutamine synthetase (GS) is essential for maintaining and promoting stem‐like characteristics of liver cancer cells during glutamine starvation. Mechanistically, glutamine starvation activates Rictor/mTORC2 to induce HDAC3‐mediated deacetylation and stabilization of GS. Rictor is significantly correlated with the expression of GS and stem marker OCT4 at tumor site, and closely correlates with poor prognosis of hepatocellular carcinomas. Inhibiting components of mTORC2‐HDAC3‐GS axis decrease TICs and promote xenografts regression upon glutamine‐starvation therapy. Collectively, the data provides novel insights into the role of Rictor/mTORC2‐HDAC3 in reprogramming glutamine metabolism to sustain stemness of cancer cells. Targeting Rictor/HDAC3 may enhance the efficacy of glutamine‐starvation therapy and limit the rapid growth and malignant progression of tumors. Cancer cells are addicted to glutamine. When glutamine is deficient, mTORC1 is inhibited but mTORC2 is activated to regulate metabolic balance. Rictor/mTORC2 activates histone deacetylase HDAC3, which stabilizes glutamine synthase (GS) expression. GS promotes endogenous glutamine synthesis and maintains intracellular glutamine balance, which endows cancer cells with stem cell characteristics and promotes the malignant progression of cancer.

Rhododendron jiucaipingensis Jian Xu & M. T. An, sp. nov . (Ericaceae), a new species of R. subgen. Hymenanthes , subsect. Argyrophylla , from northwestern Guizhou, China, is described and illustrated. It is an evergreen shrub 1.5–3.0 m tall, characterized by green, densely white-tomentose current-year branchlets, leaves crowded at branch apices (5.5–9.5 × 2.5–4.0 cm) with 8–11 pairs of lateral veins, 10 stamens, and cylindric capsules 1.2–2.0 cm long. The new species is morphologically most similar to R. hypoglaucum and R. argyrophyllum , but it is readily distinguished by having densely white-tomentose current-year branchlets, fewer lateral veins (8–11 pairs), a double-layered white indumentum on the abaxial surfaces of young leaves, and 10 stamens. Phylogenetic analysis based on a whole-genome SNP dataset robustly resolves R. jiucaipingensis as a distinct lineage within subsect. Argyrophylla , positioned as sister to the monophyletic clade of five congeneric species with high support (SH-aLRT = 100%, UFBoot = 100%). This molecular evidence, congruent with diagnostic morphological characters, supports the recognition of R. jiucaipingensis as a species new to science.

Hypericum liboense M.T.An & T.R.Wu, sp. nov. (Hypericaceae) is a newly described species found in the Maolan National Nature Reserve of Guizhou Province, where it grows in rocky habitats without soil on karst mountain tops. In this study, key morphological characters were compared between the new species and the other known Hypericum species of Hypericaceae. DNA sequences were extracted from the leaves of the new species, with nuclear gene sequences (ITS) generated to reconstruct phylogenetic trees and describe its phylogenetic position in relation to other species of Hypericum . Our results show that the proposed new species has the typical characteristics of the genus Hypericum in morphology being similar to Hypericum monogynum , but differing in its sessile and semi-clasped leaves, long elliptical to long circular leaf blades, thickly papery to thinly leathery, with entire and wavy leaf margins. The abaxial side of the leaves is covered with white powder, giving them a grey-white appearance. The main lateral veins of the leaves are 8–15-paired, and the midvein on both sides is convex. The main lateral veins and midvein branch are conspicuous, with tertiary venation forming a network on the leaf surface and appearing prominently sunken. The inflorescences are 1–3-flowered, with a large calyx and conspicuous veins. The molecular phylogenetic analysis (PP = 1.00) provided substantial evidence for the proposition of H. liboense as a new species within Hypericum . Morphological and molecular evidence is presented, corroborating the proposition of the new species, including a comprehensive account of the distinctive morphological attributes of H. liboense , along with its key distinguishing features from similar species.

This paper describes a new species of the genus Euonymus from Guizhou Province in southwestern China, Euonymus maotaiensis . The new species is morphologically similar to E. chloranthoides but can be distinguished by several key characteristics: broadly lanceolate leaves (as opposed to elliptic to oblong-elliptic), longer petioles (5–12 mm vs. 1–2 mm), longer peduncles (4–9 cm vs. 1–2 cm), 4- or 5-merous flowers (vs. strictly 5-merous), suborbicular petals with the upper half completely recurved abaxially (vs. planar petals), and indehiscent, 4–5 shallowly sulcate capsules (vs. 5-lobed capsules dehiscent to near the midpoint). These morphological differences are further supported by molecular phylogenetic analyses.