Primary cilia—those solitary, microtubule-based projections extending from the surface of most eukaryotic cells—are increasingly recognized not merely as cellular appendages, but as sophisticated signaling hubs. By compartmentalizing specific receptors (e.g., GPCRs) and effectors within a microdomain guarded by the transition zone, these organelles function effectively as high-gain sensors capable of integrating mechanical stimuli with metabolic cues. In this review, we examine the pivotal role of primary cilia across the nervous, bone-vascular, and renal landscapes, arguing for a unified “mechano-metabolic coupling” framework. Here, conserved ciliary modules are not static; rather, they are differentially deployed to uphold systemic homeostasis. Within the central nervous system, we position primary cilia as upstream integrators. We highlight how hypothalamic neuronal cilia concentrate metabolic receptors, such as the melanocortin 4 receptor (MC4R), to interpret energy status. Moreover, the recent identification of serotonergic “axon-cilium synapses” points to a direct mode of neurotransmission, wherein 5-HT6 receptors drive nuclear signaling and chromatin accessibility to rapidly modulate gene expression. Through these mechanisms, central cilia modulate sympathetic tone and neuroendocrine output, effectively establishing the mechanical and metabolic “boundary conditions” under which peripheral organs operate. Dysfunction in these central hubs is linked to obesity and neurodevelopmental disorders, including Bardet-Biedl syndrome. In peripheral tissues, cilia serve as versatile mechanotransducers that convert physical forces into biochemical responses. Regarding the bone-vascular system, we discuss the translation of mechanical loads and fluid shear stress into structural remodeling. In osteoblasts, specifically, ciliary integrity is intrinsically linked to cholesterol and glucose metabolism, fine-tuning the balance between Hedgehog and Wnt/β-catenin signaling to govern osteogenesis and bone repair. A similar dynamic exists in the vasculature, where endothelial cilia sense shear stress to modulate KLF4 expression and endothelial-to-mesenchymal transition—processes critical for valvulogenesis and vascular remodeling. Meanwhile, in the kidney, tubular cilia act as terminal effectors within a “shear-cilia-metabolism” axis. Here, fluid shear stress engages ciliary signaling to trigger AMPK-mediated lipophagy and mitochondrial biogenesis, thereby securing the ATP supply required for solute transport. Notably, dysregulation of this axis leads to metabolic reprogramming and aberrant proliferation, acting as a hallmark driver of cystogenesis in polycystic kidney disease (PKD). Crucially, this review attempts to dissect the often-conflated logic of cross-system integration by distinguishing 3 non-equivalent pathways: direct communication via ciliary extracellular vesicles, though this remains largely hypothetical in long-range signaling; “physiology-mediated cascades”, where ciliary dysfunction in a single organ—such as the kidney—precipitates systemic pathology through hemodynamic and metabolic shifts (e.g., altered blood pressure, fluid volume, or uremic toxins); and “parallel molecular defects”, where shared genetic mutations in ubiquitous components like the IFT machinery cause simultaneous, independent failures across multiple organ systems. Building on these distinctions, we propose a nested-loop model that links central set-points with peripheral feedback via physiological variables. Furthermore, we construct a “causality-to-translation” roadmap that pinpoints structural repair (e.g., targeting IFT assembly) and metabolic rescue (e.g., AMPK activation or autophagy induction) as promising therapeutic avenues. Ultimately, this framework provides a theoretical basis for deciphering the shared pathological mechanisms of multisystem ciliopathies, offering a strategic guide for the development of targeted interventions that go beyond symptomatic treatment.

Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease mediated by T lymphocytes， and it can progress to liver cirrhosis or even liver failure without timely intervention. As a natural flavonoid compound， naringenin （NAR） shows a potential value in the prevention and treatment of AIH through multiple mechanisms such as remodeling immune homeostasis， targeted inhibition of inflammatory pathways， antioxidation， regulating hepatocyte metabolism and apoptosis， improving mitochondrial function， and regulating intestinal flora. However， the clinical translation and application of NAR is limited by issues such as low bioavailability and insufficient efficiency of liver-targeted delivery. This article systematically reviews the mechanism of action of NAR in the prevention and treatment of AIH， explores the potential signaling pathways involved in this process， and analyzes existing challenges in its translation and application and future research directions， so as to provide a reference for further research on NAR and its application in the prevention and treatment of AIH.

Global procurement of health products is an important way for multilateral organizations in the health field to perform their functions.As one of the most important multilateral organizations in the global health field today,the Global Fund to Fight AIDS,Tuberculosis and Malaria occupies a huge share of the global procurement market for health products.This article introduces in detail the procurement methods of the Global Fund and the quality standards of its procured products;also it describes and analyzes the total amount of funds procured by the Global Fund,the types of procured health products,the main supply countries and their changing trends over time.Corresponding policy suggestions therefore are proposed for China to better participate in the governance of global health and for Chinese related companies to enter the international procurement market.

United Nations(UN)agencies are key actors in global procurement of health products,with the United Nations Children's Fund(UNICEF)currently accounting for the largest share of UN procurement expenditures.This study developed a conceptual framework to analyze the processes of UN's global procurement for health products.Based on this framework,the study analyzed the mechanisms and key characteristics of UN procurement practices,identified potential challenges faced by Chinese products and suppliers seeking to engage with the UN's global procurement.The findings indicate a steady increase in the volume of Chinese products procured and their alignment with the UN's sustainable procurement policies.However,Chinese suppliers still face notable barriers,including gaps in technical standards,bidding and contracting capacities,and price competitiveness.In addition,the strategic compliance capabilities of Chinese suppliers and products,such as the ability to offer strategically valuable products and build long-term partnership,remains limited.Based on this,the study recommends that China enhance its participation and influence in the UN health procurements by stabilizing the production capacity,promoting knowledge-sharing among suppliers to enhance their engagement capabilities,and improving the long-term strategic competitiveness of Chinese enterprises in the global market.

Glycoengineering was carried out in the mammalian cell line CHO for the production of pro-tein-based drugs.Firstly,the genome sequence of the Rosa26 locus of CHO cells was determined,the gRNA sequences were designed,and the landing pad was integrated into the Rosa26 locus of CHO cells by CRISPR/Cas9 technology.Three targeting vectors co-expressed by glycosyltransferases,which are β-1,4 galactosyltransferase(B4GALT1),α-2,6-sialyltransferase 1(ST6GAL1)and N-acetaminoglycosyl-transferase Ⅲ(GnT Ⅲ),were constructed by overlapping PCR and seamless ligation technology,and the three glycosyltransferase genes were integrated into the CHO Rosa26 locus by Cre enzyme-mediated cassette exchange technology.PCR confirmed that three glycosyltransferases had been successfully site-directed integrated into the Rosa26 site.The mRNA expression levels of the three glycosyltransferases were more than 50 000-fold by qRT-PCR,and the protein expression levels of the three glycosyltrans-ferases were more than 4-fold via western blotting(P＜0.001).A CHO-engineered cell line with three glycosyltransferases integrated into Rosa26 site was successfully constructed.

Objective To explore the role of forkhead box protein p2(FOXP2)in the proliferation and metastasis of uterine fibroid cells by regulating glycolysis mediated by Hedgehog signaling pathway.Methods Fresh hysteromyoma tissue was obtained from 10 patients who underwent myomectomy in the Department of Gynecology of Guizhou Provincial Hospital of Workers,and hysteromyoma cells were digested and separated.Cells were transfected with lentivirus shRNA targeting FOXP2(sh-FOXP2),negative control(sh-NC)and FOXP2 overexpression vectors(oe-FOXP2),and negative control(oe-NC).Colony formation test and Transwell assay were used to evaluate the cell proliferation and metastasis ability.Glucose uptake,lactic acid production and extracellular acidification rate(ECAR)were measured to detect the aerobic glycolysis ability of cells.A xenograft tumor model was established by up-regulating uterine leiomyoma cells with FOXP2 to explore the regulatory effect of FOXP2 in vivo.Results Compared with oe-NC group,the cell viability,colony number,migrating cell number,glucose uptake,lactic acid production and ECAR in oe-FOXP2 group decreased significantly(P＜0.05).Compared with sh-NC group,the cell viability,colony number,migrating cell number,glucose uptake,lactic acid production and ECAR of uterine fibroids in sh-FOXP2#1 and sh-FOXP2#2 groups increased significantly(P＜0.05).Compared with oe-NC+vector group,the number of colonies,migrating cells,glucose uptake,lactic acid production,ECAR,Shh and Gli proteins in oe-FOXP2+vector group decreased significantly(P＜0.05).Compared with oe-FOXP2+vector group,the number of colonies,migrating cells,glucose uptake,lactic acid production,ECAR,Shh and Gli proteins in oe-FOXP2+SAG group were significantly increased(P＜0.05).Compared with oe-NC group,the tumor weight,the proportion of Ki-67 positive cells and the proteins of Shh,Gli,GLUT1 and PGAM1 in oe-FOXP2 group decreased significantly(P＜0.05).Compared with oe-FOXP2 group,the tumor weight,the proportion of Ki-67 positive cells and the proteins of Shh,Gli,GLUT1 and PGAM1 in oe-FOXP2+SAG group increased significantly(P＜0.05).Conclusions FOXP2 participates in the proliferation and metastasis of uterine leiomyoma cells by regulating glycolysis mediated by Hedgehog signaling pathway.

United Nations(UN)agencies are key actors in global procurement of health products,with the United Nations Children's Fund(UNICEF)currently accounting for the largest share of UN procurement expenditures.This study developed a conceptual framework to analyze the processes of UN's global procurement for health products.Based on this framework,the study analyzed the mechanisms and key characteristics of UN procurement practices,identified potential challenges faced by Chinese products and suppliers seeking to engage with the UN's global procurement.The findings indicate a steady increase in the volume of Chinese products procured and their alignment with the UN's sustainable procurement policies.However,Chinese suppliers still face notable barriers,including gaps in technical standards,bidding and contracting capacities,and price competitiveness.In addition,the strategic compliance capabilities of Chinese suppliers and products,such as the ability to offer strategically valuable products and build long-term partnership,remains limited.Based on this,the study recommends that China enhance its participation and influence in the UN health procurements by stabilizing the production capacity,promoting knowledge-sharing among suppliers to enhance their engagement capabilities,and improving the long-term strategic competitiveness of Chinese enterprises in the global market.

From the perspective of circular RNA forkhead box protein O3(circFOXO3) regulating glycolysis in osteoarthritis(OA) chondrocytes, this study investigated the mechanism by which Tougu Xiaotong Capsules(TGXTC) alleviated OA degeneration. In in vivo experiments, after randomized grouping and relevant interventions, morphological staining was used to observe structural changes in cartilage tissue. The mRNA level of circFOXO3 in cartilage tissue was detected by real-time quantitative PCR(RT-qPCR). Western blot analysis was used to detect changes in the expression of glucose transporter 1(GLUT1), hexokinase 2(HK2), pyruvate kinase M2(PKM2), lactate dehydrogenase A(LDHA), and matrix metalloproteinase 13(MMP13). In in vitro experiments, fluorescence in situ hybridization(FISH) was used to detect circFOXO3 expression in chondrocytes from each group. A lentiviral vector was used to construct circFOXO3-silenced(sh-circFOXO3) chondrocytes. RT-qPCR was used to analyze the changes in circFOXO3 levels after silencing, and Western blot was used to assess the regulatory effects of TGXTC on GLUT1, HK2, PKM2, LDHA, and MMP13 proteins in interleukin-1β(IL-1β)-induced chondrocytes under sh-circFOXO3 conditions. Masson staining and alcian blue staining results showed that the cartilage layer structure in the TGXTC and positive drug groups was improved compared with that in the model group. The mRNA level of circFOXO3 was significantly upregulated in both the TGXTC and positive drug groups, while the expression of the above-mentioned proteins was significantly reduced. FISH results showed that TGXTC upregulated the fluorescence intensity of circFOXO3 in IL-1β-induced chondrocytes. In the circFOXO3 silencing experiment, compared with the IL-1β group, circFOXO3 levels in the IL-1β + sh-circFOXO3 group were significantly decreased. Compared with the IL-1β + TGXTC group, circFOXO3 levels were significantly reduced in the IL-1β + sh-circFOXO3 + TGXTC group. Western blot results indicated that the elevated levels of GLUT1, HK2, PKM2, LDHA, and MMP13 proteins in chondrocytes of the IL-1β group were significantly inhibited by TGXTC intervention. However, this regulatory effect was attenuated after circFOXO3 silencing. In conclusion, TGXTC alleviate glycolytic metabolism disorder in OA chondrocytes and delay OA degeneration by regulating circFOXO3.
Chondrocytes/metabolism* ; Animals ; Drugs, Chinese Herbal/administration & dosage* ; RNA, Circular/metabolism* ; Osteoarthritis/genetics* ; Glycolysis/drug effects* ; Humans ; Forkhead Box Protein O3/metabolism* ; Male ; Capsules ; Matrix Metalloproteinase 13/genetics*

Global procurement of health products is an important way for multilateral organizations in the health field to perform their functions.As one of the most important multilateral organizations in the global health field today,the Global Fund to Fight AIDS,Tuberculosis and Malaria occupies a huge share of the global procurement market for health products.This article introduces in detail the procurement methods of the Global Fund and the quality standards of its procured products;also it describes and analyzes the total amount of funds procured by the Global Fund,the types of procured health products,the main supply countries and their changing trends over time.Corresponding policy suggestions therefore are proposed for China to better participate in the governance of global health and for Chinese related companies to enter the international procurement market.

Glycoengineering was carried out in the mammalian cell line CHO for the production of pro-tein-based drugs.Firstly,the genome sequence of the Rosa26 locus of CHO cells was determined,the gRNA sequences were designed,and the landing pad was integrated into the Rosa26 locus of CHO cells by CRISPR/Cas9 technology.Three targeting vectors co-expressed by glycosyltransferases,which are β-1,4 galactosyltransferase(B4GALT1),α-2,6-sialyltransferase 1(ST6GAL1)and N-acetaminoglycosyl-transferase Ⅲ(GnT Ⅲ),were constructed by overlapping PCR and seamless ligation technology,and the three glycosyltransferase genes were integrated into the CHO Rosa26 locus by Cre enzyme-mediated cassette exchange technology.PCR confirmed that three glycosyltransferases had been successfully site-directed integrated into the Rosa26 site.The mRNA expression levels of the three glycosyltransferases were more than 50 000-fold by qRT-PCR,and the protein expression levels of the three glycosyltrans-ferases were more than 4-fold via western blotting(P＜0.001).A CHO-engineered cell line with three glycosyltransferases integrated into Rosa26 site was successfully constructed.